Natural history of optic pathway gliomas in a cohort of unselected patients affected by Neurofibromatosis 1

Abstract

Optic pathway glioma (OPG) represents the most common central nervous system tumor in children with Neurofibromatosis type-1 (NF1). Although overall survival is usually good, no clear prognostic factors have been identified so far. We assessed the natural history of OPG in a cohort of unselected patients affected by NF1. We retrospectively evaluated 414 consecutive patients affected by NF1 and referred to our NF1 clinic before age 6. Average follow-up was 11.9 years: 52 out of 414 patients had OPG with a total cumulative incidence of 15.4% at age 15 (Kaplan–Meier estimate) and a statistically significant difference according to sex. Brain and orbit MRI was performed in 44.7% of patients: 34.6% for screening purposes and 65.4% because of the presence of neurological, ocular or other symptoms. OPG was diagnosed in 12.5% of cases in the first group, whereas in 36.4% in the latter group (p = 0.001). Clinical management was conservative in most patients, while 8 of them underwent therapy mainly because of visual deterioration. OPG was diagnosed earlier in treated patients, but the difference was not statistically significant. Conversely, all patients who underwent screening MRI had normal visual outcome. In conclusion, OPG location does not correlate with need for treatment; female patients were more frequently affected by OPG but not more frequently treated. OPG diagnosis by screening MRI does not affect the natural history of the tumor.

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Stereotactic radiosurgery for small brain metastases and implications regarding management with systemic therapy alone

Abstract

While stereotactic radiosurgery (SRS) has been shown effective in the management of brain metastases, small brain metastases (≤10 mm) can pose unique challenges. Our aim was to investigate the efficacy of SRS in the treatment of small brain metastases, as well as elucidate clinically relevant factors impacting local failure (LF). We utilized a large, single-institution cohort to perform a retrospective analysis of patients with brain metastases up to 1 cm in maximal dimension. Clinical and radiosurgical parameters were investigated for an association with LF and compared using a competing risk model to calculate cumulative incidence functions, with death and whole brain radiotherapy serving as competing risks. 1596 small brain metastases treated with SRS among 424 patients were included. Among these tumors, 33 developed LF during the follow-up period (2.4% at 12 months following SRS). Competing risk analysis demonstrated that LF was dependent on tumor size (0.7% if ≤2 mm and 3.0% if 2–10 mm at 12 months, p = 0.016). Other factors associated with increasing risk of LF were the decreasing margin dose, increasing maximal tumor diameter, volume, and radioresistant tumors (each p < 0.01). 22 tumors (0.78%) developed radiographic radiation necrosis following SRS, and this incidence did not differ by tumor size (≤2 mm and 2–10 mm, p = 0.200). This large analysis confirms that SRS remains an effective modality in treatment of small brain metastases. In light of the excellent local control and relatively low risk of toxicity, patients with small brain metastases who otherwise have a reasonable expected survival should be considered for radiosurgical management.

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Hypothermic Suppression of Epileptiform Bursting Activity of a Hyppocampal Granule Neuron Possessing Thermosensitive TRP Channels (a Model Study: Biophysical and Clinical Aspects)

Synchronous burst discharges of action potentials (APs) of neurons are typical manifestations of cerebral epileptiform activity; such discharges are reflected in EEG as burst-suppression episodes. For elimination of drug-resistant epileptogenic foci, therapeutic hypothermia (controlled decrease in the body temperature) is increasingly used; at the same time, the mechanisms of its therapeutic effect remain largely unknown. We investigated one of the respective possible mechanisms on a model of the granule neuron (GN) of the hippocampal dentate gyrus. These cells are the first links in three-synaptic neuronal chains of the hippocampus; the latter is the brain region where sources of epileptiform activity are often localized. In the somatodendritic membrane of the GN model, thermosensitive channels of the TRP family, which conduct a depolarizing current, were included along with other ion channels inherent in these neurons. It has been found that such channels are indeed expressed in GNs. In response to tonic synaptic excitation uniformly distributed over the dendrites, the GN at 37°C (normothermia) generated periodic multipulse burst discharges. Lowering the temperature to 36, 34, 32, and 30°C (borders of weak, moderate, moderately deep, and deep therapeutic hypothermia, respectively) led to degradation of the bursting patterns and their transformation into low-frequency trains of separate APs. Precisely at these temperatures, is the depolarizing current through TRP channels deactivated. The phenomenon of degradation of bursting activity generated by the model GN corresponded to a multifold decrease in the amplitude, duration, and repetition frequency of the burst-suppression episodes in EEGs of newborn infants suffering from hypoxic-ischemic CNS injury, which we observed in clinics under conditions of moderate hypothermia (34°C) used for treatment of such patients. These observations allow us to suggest that hypothermic suppression of bursting discharges of hippocampal neurons possessing thermosensitive TRP channels may be one of the mechanisms of the therapeutic effect of hypothermia.

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Decision-Level Fusion-Based Structure of Autism Diagnosis Using Interpretation of EEG Signals Related to Facial Expression Modes

A structure of decision-level fusion-based autism diagnosis using analysis of EEG signals related to presentation of facial expression modes has been proposed. EEG signals of autistic and normal children were recorded during processing images of emotional facial expression modes, such as sadness, happiness, and calmness. Then brain signals were mapped into the feature space by applying a novel hybrid model utilizing the brain potentials recorded during the examination task. The aim of mapping was to achieve separation of the autistic samples from normal ones with the highest precision. The created map provides the feature vectors that reflected spatial, temporal, and spectral data, as well as the coherence degrees for distinct areas of the brain. The mapping process was optimized using a genetic algorithm by assigning weighs to the feature vectors. Then the feature vectors corresponding to the three facial expressions of emotional modes were classified by support vector machines. Finally, using decision-level fusion through a majority voting rule, we see that the proposed structure is able to effectively distinguish the autistic individuals from normal ones.

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Erratum to: Parameters of the P300 Potential in Mild Neurocognitive Disorders of Different Etiologies

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Vasyl’ M. Moroz – 75 years

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Contrast-Dependent Restructuring of Neuronal Visual Receptive Fields in the Cat Extrastriate Cortex

Spatial modifications of neuronal visual receptive fields (RFs) in the cat extrastriate cortex were studied. The response properties and spatial organization of the RFs of area 21a neurons were investigated using visual stimuli of two opposite contrasts, with particular attention to the stationary structure of these RFs. It was found that the infrastructure of the RF of a visually sensitive neuron undergoes certain restructuring related to the contrast of the visual stimuli used. In most cases, discharge centers of the RF subfields changed their response profile and spatial localization within the RF depending on the stimulus contrast. Stationary RFs defined by presentation of flashing spots of two opposite contrasts (bright and dark) differed from each other quantitatively and qualitatively, indicating the influence of background illumination on the pattern of neuronal responses. It is hypothesized that the RF surrounding significantly influences central processing of incoming visual information and image recognition in the extrastriate cortex.

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GABA A Receptors: Involvement in the Formation of Respiratory Reactions to Hypoxic Stimulation under Conditions of Mitochondrial Dysfunction

In experiments on Wistar rats, the role of the state of GABA_A receptors in the formation of respiratory responses to hypoxic loading was studied under conditions of the norm and experimental mitochondrial dysfunction; the latter was induced by single systemic injections of 3 mg/kg rotenone, a nonselective blocker of complex I in the respiratory chain of the mitochondria. Volume-time parameters of respiration were characterized according to the parameters of respiratory EMG discharges of the diaphragmatic muscle (amplitude, frequency, and integral intensity). Changes in EMG activity of the diaphragm induced by inhalation of a hypoxic gas mixture (12% О₂ + 88% N₂) were estimated prior to and after injections of the blocker of GABAA and GABAB receptors bicuculline (bicuculline methiodide, 1.0 mg/kg) in control rats and animals with mitochondrial dysfunction. The development of mitochondrial dysfunction was accompanied by suppression of the respiratory reaction to hypoxic loading, which was manifested in a dramatic decrease in the frequency and integral intensity of EMG discharges of the diaphragmatic muscle. These data can be considered an indication of the considerable involvement of GABAA receptors localized at the postsynaptic membranes of peripheral chemoreceptors in the formation of respiratory response to hypoxic stimulation (including the stage of depression of ventilation); this was observed in both control rats and animals with mitochondrial dysfunction. The involvement of a GABA-ergic link in the formation of respiratory activity related to hypoxic stimulation acquires special significance under conditions of experimental mitochondrial dysfunction leading to occlusion of afferent impulsation coming from peripheral chemoreceptors.

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Computer Simulation of Molecular Interaction Between Baclofen and the GABA B Receptor

In our previous work [1], we have reconstructed the spatial structure of a full-size GABA_B receptor using computer simulation. Considering the fact that baclofen is a selective agonist of this receptor, we attempted to search for binding sites of the molecule of this agent with the extracellular domain of a GABA_B1 receptor subunit, assessed the molecular dynamics of their interaction, and calculated the energy of nonvalent interactions between the receptor and agonist molecule under study. A molecular docking approach used to estimate interactions between baclofen and the GABA_B receptor extracellular domain allowed us to choose three sites for possible binding of the baclofen molecule to the receptor. Using molecular dynamics simulation, we identified two sites capable of providing stable coupling of baclofen with the GABA_B receptor.

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Effects of Hindbrain Infusion of an Estrogen Receptor Antagonist on Estrogenic Modulation of Eating Behavior

Estradiol (E₂) inhibits eating behavior in females via activating estrogen receptors (ERs) within the brain. Activation of hindbrain ERαs has been shown to be sufficient to inhibit eating behavioral pattern. To investigate the involvement of hindbrain ERαs in estrogenic control of eating behavior, intracerebroventricular infusion (4th i.c.v.) of an estrogen receptor antagonist, ICI 182780 (ICI), was performed in ovariectmized female rats. Significantly lower daily food intake was observed in rats after estradiol benzoate (EB) injections. The effect of EB on food intake was significantly compromised by 4th i.c.v. infusions of both 4 and 8 nM ICI solutions. The results suggest that hindbrain infusions of ICI can significantly attenuate the inhibitory effect of E₂ on food intake. Importantly, 4th i.c.v. infusions during 12 days exerted no effect per se on eating. Further, there was no difference in the number of ERα immunopositive neurons in the selected hypothalamic nuclei and nucl. tractus solitarius. We conclude that the 4th i.c.v. infusions with ICI attenuated the exogenous estrogenic effect on food intake in ovariectomized rats, and the hindbrain is an important site pro viding estrogenic control of food intake.

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Features of EEG Activity Related to Realization of Cyclic Unimanual and Bimanual Hand Movements in Humans

In 10 tested dextral subjects, EEG activity was recorded during the performance of unimanual and bimanual cyclic movements of the hands and fingers. The movements corresponded to clenching the fingers into a fist and the subsequent unclenching of the fingers. The test consisted of four successive stages, the resting state, movement of the left hand, that of the right hand, and movement of both hands. The dependences between the spectral power and coherence of the respective EEG samples on the type of the test performed, on the type of the movement (uni- or bimanual), and on the laterality of the latter in the case of the unimanual movement were examined. The results obtained allow us to propose the following conclusions: (i) α and β EEG rhythms are characterized by different functional importance with respect to manual motor activity; (ii) neural control of bimanual movements cannot be considered "a sum of the controls" of unimanual movements, and (iii) control of bimanual movements may be largely based on the control of the movement by a subdominant upper limb.

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Combined spontaneous bacterial empyema and peritonitis in cirrhotic patients with ascites and hepatic hydrothorax

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Anwar Mohamed, Mohammed Atef, Ayman Alsebaey, Mahmoud Musa Elhabshy, Mohsen Salama
Background and study aims: Spontaneous bacterial empyema (SBEM) is an underestimated condition in patients with ascites and hepatic hydrothorax with a high mortality. This study aimed to find whether spontaneous bacterial peritonitis (SBP) is a prerequisite for SBEM. Patients and methods: 3000 HCV-related cirrhotic patients with ascites and hydrothorax were screened for the presence of SBP (ascitic fluid neutrophils >250/mm³) and SBEM (positive pleural fluid culture and neutrophils >250/mm³ or negative pleural fluid culture and neutrophils >500/mm³ with no evidence of pneumonia/parapneumonic effusion on chest radiograph or CT). Results: The prevalence of SBEM in cirrhotic patients was 1.2% (36/3000) unlike SBP (1.6%; 48/3000). SBEM was detected in 51.4% of the patients with hepatic hydrothorax (36/70). A total of 70 patients had concomitant ascites and hydrothorax, namely SBP (n=17), SBEM (n=5), and dual SBP and SBEM (n=31), whereas 17 patients had sterile concomitant ascites and hydrothorax. Age, sex, liver function, kidney function tests, complete blood count, INR, MELD, MELD-Na, blood chemistry, and culture/sensitivity for ascitic and pleural fluid were statistically not different (p>0.05) between SBP and dual SBP and SBEM patients. Escherichia coli and Klebsiella pneumoniae were detected in the culture. From univariate analysis, no predictors of dual SBP and SBEM were detected. Conclusion: SBEM is a part of SBP in cirrhotic patients with ascites and hydrothorax.



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Percutaneous ultrasound-guided fiducial marker placement for liver cancer robotic stereotactic radio-surgery treatment: A comparative analysis of three types of markers and needles

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Maria Marsico, Tommaso Gabbani, Sarah Lunardi, Andrea Galli, Maria Rosa Biagini, Vito Annese
Background and study aimsPercutaneous placement of fiducial markers is required to perform stereotactic body radiation therapy (SBRT) for liver neoplastic lesions. This prospective trial was designed to evaluate the feasibility and safety of percutaneous ultrasound-guided placement of three different types of markers in patients with liver cancer referred for SBRT.Patients and methodsFifty patients underwent percutaneous ultrasound-guided implantation of a fiducial marker in the liver. Three sizes of needles were used: 25 gauge (G), 22G, and 17G. The 25G and 22G needles contained gold anchor markers of 0.28×10mm and 0.4 ×10mm size, respectively. In contrast, the 17G needle contained a gold grain marker of 1×4mm. Each patient received 1–6 markers, depending on lesion size and numbers. Technical feasibility and the occurrence of adverse events were registered. Computed tomography scans were acquired prior to SBRT to evaluate the location, visibility, or complications related to the markers.ResultsA total of 163 needles were used to deliver 163 markers in 50 patients. No major complications occurred. Minor complication occurrence rate was 12%. The total complication occurrence for all type of markers was 8.5%. No complications were observed with the use of the gold anchor marker of 0.4 ×10mm size. Variance analysis of the three markers showed a significant difference in the frequency of complications amongst the three markers (p<0.01).ConclusionPercutaneous ultrasound-guided placement of fiducial markers for SBRT of liver neoplastic lesions is safe and feasible. In our series, the 22G needle showed some advantage in terms of handling and safety when compared with the 25G and 17G needles. In addition, the gold anchor marker of 0.4 ×10mm size displayed a lower percentage of displacement.



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Prevalence of hepatitis C virus genotypes and subtypes in Lebanese population and major high risk groups

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Antoine Abou Rached, Cesar Yaghi, Leda Khalil, Jowana Saba, Walid Ammar
Background and study aimsThe prevalence of hepatitis C in Lebanon is low. It is estimated at 0.2% of the total population. The aim of our study is to evaluate the exact prevalence of each genotype on a large scale population and in each potential source of infection.Patients and methodsWe reviewed all the data in the Ministry of Public Health related to patients who have submitted their file for treatment during a period of 9years ranging from January 2005 till December 2013.ResultsThe genotype distribution in 1031 Lebanese patients was as following: Genotype 1 was the most predominant representing 47% followed by genotype 4 representing 34% then genotype 3 representing14%. Concerning sex distribution and routes of infection, there was a male predominance in intravenous drug users (IVDU), whereas approximately equal distribution was noted in haemodialysis and transfusion groups. A female predominance was noted in the "unknown" mode of infection. Concerning age distribution and routes of infection, a mean age of 27 was noted in the IVDU group, whereas mean age of 60 in the transfusion group and 50 in the haemodialysis group. In patients who acquired the infection post transfusion or during haemodialysis, genotype 1 was the most predominant, whereas in IVDU, genotype 3 was the most predominant. Concerning sub-genotyping: subtype 1b was the most predominant (84%) in genotype 1. in genotype 2 subtype b with 75%, all genotype 3 were subtype a, in genotype 4 subtype a represents 50% of genotype followed by subtype e in 30%.ConclusionOur data concerning Lebanese population demonstrate that genotype 1 is the most prevalent genotype followed by genotype 4. In IVU, we noted genotype-3 and -1 being the most prevalent in relation to clustering in this high risk group. This distribution differs from most surrounding countries and all other Arab countries.



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APRI test and hyaluronic acid as non-invasive diagnostic tools for post HCV liver fibrosis: Systematic review and meta-analysis

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Magdy Amin El Serafy, Abdel Meguid Kassem, Heba Omar, Mohammad Shaaban Mahfouz, Maissa El Said EL Raziky
Background and study aimsHepatitis C virus (HCV) accounts for a sizable proportion of chronic liver disease cases and represents the most common indication for liver transplantation. Precise diagnosis of hepatic fibrosis stage is considered a funnel-neck in proper management and follow-up of HCV-infected patients. Given the possible complications of liver biopsy, a non-invasive method for assessing hepatic fibrosis is needed. This study aimed to evaluate the diagnostic accuracy of APRI and hyaluronic acid as non-invasive diagnostic assessment tools for post HCV liver fibrosis.Patients and methodsSystematic literature searching identified studies performed on Egyptian territory to evaluate APRI and hyaluronic acid as non-invasive tests of fibrosis and using liver biopsy as the reference standard. Meta-analysis was performed for areas with an adequate number of publications. Validation of meta- analysis on APRI was done on a subset of 150 treatment-naïve post-hepatitis C patients.ResultsBoth APRI and hyaluronic acid have superior predictive power for hepatic cirrhosis (F4) than for significant fibrosis (F2-F3). The pooled estimate for sensitivities and specificities of APRI and hyaluronic acid to diagnose F4 were (84% and 82%) and (83% and 89%) respectively. In the subgroup of treatment naïve post-hepatitis C patients, APRI had higher diagnostic performance to diagnose liver cirrhosis with 93.8% sensitivity and 72.4% specificity (AUC; 0.908, 95%CI; 0.851–0.965, p-value; <0.001) compared to its accuracy to diagnose significant hepatic fibrosis with 65.1% sensitivity and 77.8% (AUC; 0.685, 95% CI; 0.59–0.78, p-value; 0.001).ConclusionAPRI score and hyaluronic acid levels are simple and reliable non-invasive markers to detect advanced fibrosis among post-hepatitis C patients.



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Evaluation of gastro-oesophageal reflux disease in wheezy infants using 24-h oesophageal combined impedance and pH monitoring

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ahmed Abdallah, Tarek El-Desoky, Khalid Fathi, Wagdi Fawzi Elkashef, Ahmed Zaki
Background and study aimsGastro-oesophageal reflux disease (GERD) is incriminated as a cause of non-asthmatic infantile wheeze. To date, no diagnostic test is considered standard for GERD-related airway reflux diagnosis. Oesophageal combined multiple channel intraluminal impedance and pH (MII-pH) monitoring is proposed to be a sensitive tool for evaluation of all GERD including infantile wheeze. We aimed to determine the GERD prevalence amongst wheezy infants in the first year of life using combined MII-pH versus pH monitoring alone and evaluate the sensitivity and specificity of objective MII-pH monitoring parameters in GERD-associated infantile wheeze diagnosis compared to those of lipid-laden macrophage index (LLMI).Patients and methodsThirty-eight wheezy infants below 1year of age were evaluated for GERD using oesophageal combined MII-pH monitoring and LLMI.ResultsTotally, 60.5% of cases had abnormal MII-pH; only 7.9% of them had abnormal pH monitoring. LLMI was significantly higher in wheezy infants with abnormal MII-pH than infants with normal MII-pH monitoring (112±88 versus 70±48; P=0.036). The current definitions of abnormal MII-pH study, reflux index≥10% and distal reflux episodes≥100, had low sensitivity (23%) but high specificity (100% and 96%, respectively) in GERD-related aspiration diagnosis defined by LLMI≥100. Using ROC curves, bolus contact time≥2.4% and proximal reflux episodes≥46 had 61% and 54% sensitivity and 64% and 76% specificity, respectively, in GERD-related aspiration diagnosis.ConclusionCombined MII-pH is superior to pH monitoring in reflux-associated infantile wheeze diagnosis. Objective data including proximal reflux episodes and bolus contact time should be combined with the current parameters used in reflux-associated infantile wheeze diagnosis.



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Relationship between liver injury and serum cytokeratin 18 levels in asymptomatic hepatitis B virus carriers and in patients with chronic hepatitis B infection

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ayhan Balkan, Nimet Yılmaz, Yasemin Balkan, Irfan Koruk, Mustafa Örkmez, Musa Aydınlı, Mehmet Koruk
Background and study aimsApoptosis represents a well-known mechanism of cell death involved in most chronic liver injuries. Our aim was to investigate the serum fragment level of cytokeratin 18 (CK18), M30, in asymptomatic hepatitis B virus (HBV) carriers and patients with chronic hepatitis B (CHB) and to evaluate the relationship between serum M30 levels and the severity of hepatic injury.Patients and methodsAsymptomatic HBV carriers (n=169), patients with CHB (n=100), and healthy control subjects (n=43) were enrolled in the study. Serum CK18 (M30) levels were analysed in all subjects. Liver biopsy for histopathological assessment was performed in asymptomatic HBV carriers and in patients with CHB infection.ResultsSerum CK18 (M30) levels were significantly higher in asymptomatic HBV carriers (198.77±77.62U/L) than in healthy control subjects (146.92±40.18U/L). Patients with CHB (283.02±147.45U/L) had significantly higher CK18 (M30) levels than asymptomatic HBV carriers (p=0.001). The diagnostic efficacy of CK18 (M30) levels in distinguishing patients with HBeAg-negative CHB from asymptomatic HBV carriers was found to be moderate (c-statistics: 0.695), and the diagnostic cut-off value of CK18 (M30) was 262U/L (specificity: 85%, sensitivity: 48%, positive likelihood ratio: 3.35, and negative likelihood ratio: 0.60). There was a positive correlation between serum CK18 (M30) levels and histological activity index scores in asymptomatic HBV carriers and patients with CHB.ConclusionsSerum CK18 (M30) levels may be a valuable indicator in distinguishing asymptomatic HBV carriers from patients with HBeAg-negative CHB when considered together with ALT and HBV-DNA levels.



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Efficacy and safety of midazolam and ketamine in paediatric upper endoscopy

Publication date: Available online 1 June 2017
Source:Arab Journal of Gastroenterology
Author(s): Ahmet Basturk, Reha Artan, Aygen Yılmaz
Background and study aimUpper endoscopy can be successfully carried out in children under deep sedation and anaesthesia. However, the best method of upper endoscopy for children who require gastrointestinal intervention has yet to be defined. The aim of this study is to investigate the efficacy and safety of the sedation induced by intravenous midazolam and ketamine during upper endoscopy in children.Patients and methodsThis study included patients ages 3–18years who had undergone upper endoscopy. All subjects received IV midazolam and ketamine. During the intervention, hypoxia, tachycardia, bradycardia, hypertension, and hypotension were recorded. After the intervention, euphoria, dysphoria, vertigo, visual problems (such as diplopia and nystagmus), and emergencies (such as arrhythmia, convulsion, and hallucination), among other findings, were recorded. Older children who were capable of expressing themselves were questioned to help determine these conditions.ResultsThe mean age of the study group was was 11.9±3.42years; 54% of the patients were females, and 46% were males. During the upper endoscopy, hypoxia occurred in 9% of patients, mild hypertension in 14%, hypotension in 5%, tachycardia in 23%, bradycardia in 8%, and flushing-urticaria in 2%. After the upper endoscopy, one of the most common complications was sore throat, which occurred in 24% of patients. Vomiting was observed in 14% of patients, dizziness in 24%, diplopia in 27%, euphoria in 3% (5 patients), dysphoria in 4%, and hallucination in 4%. Of the total patients, 4% required oxygen supply with a face mask.ConclusionThe results of our study showed that the use of IV midazolam and ketamine during upper endoscopy in children was safe and effective.



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The Horizontal Neck Lift

Facial plast Surg 2017; 33: 266-270
DOI: 10.1055/s-0037-1598054

The horizontal neck lift is a procedure involving direct excision of a horizontally oriented ellipse of skin from the neck. This procedure was developed for neck rejuvenation in patients with significant horizontal creases and excess skin of the middle and lower neck, areas that often cannot be adequately addressed with traditional techniques. This article describes the procedure, indications, patient counseling, and postoperative care in detail from the senior author's (H. M.) experience.
[...]

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Furazolidone, an Underutilized Drug for H. pylori Eradication: Lessons from Iran

Abstract

Background

Treatment success of H. pylori eradication therapy has declined worldwide largely because of increased antimicrobial resistance. New therapeutic approaches are needed, especially for countries like Iran, where resistance to commonly used drugs is already widespread and traditional H. pylori therapies produce poor cure rates.

Aim

To review the results of quadruple therapy trials containing bismuth and furazolidone in Iran.

Methods

We searched PubMed, Google scholar as well as the references of all published papers for studies conducted in Iran, utilizing furazolidone in the treatment of H. pylori infections. The target population was four drug studies that utilized a combination of bismuth, furazolidone, amoxicillin, or tetracycline plus a proton pump inhibitor.

Results

Eighteen studies with 22 arms including 1713 subjects were found. The weighted mean cure rate for 14-day studies (six studies) using 200 mg b.i.d. furazolidone was 80% intention to treat (ITT) and 87% per protocol (PP). Studies using 100 mg b.i.d. (three studies) were less effective (weighted mean ITT cure rate = 67%). One small 14-day study with furazolidone 100 mg q.i.d. achieved cure rates of 94.5% ITT and PP.

Conclusions

Although furazolidone–bismuth quadruple therapy proved relatively effective in Iran, furazolidone-containing regimens remain to be optimized. Based on these data and results from China, it appears likely that 14-day therapy containing furazolidone 100 mg t.i.d. or q.i.d. is likely to provide the highest cure rates with lowest side effects; this remains to be experimentally tested. Detailed suggestions for further development of furazolidone-containing regimens are provided.

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From Harmful Treatment to Secondary Gain: Adverse Event Reporting in Dyspepsia and Gastroparesis

Abstract

Introduction

Medical management of gastroparesis and functional dyspepsia remains difficult with several recent trials showing limited or no benefit. If treatment comes with only marginal improvements, concerns about adverse events become more relevant. We therefore examined the type and outcomes of side effects submitted to a public repository.

Methods

We searched the Federal Adverse Event Reporting System for reports associated with the treatment of dyspepsia or gastroparesis. Demographic data, medications used and implicated, side effects, and outcomes were abstracted for the years 2004–2015.

Results

Acid-suppressive agents and prokinetics were the most commonly listed medications with a stronger emphasis on prokinetics in gastroparesis. Submissions related to metoclopramide by far exceeded reports about other agents and mostly described tardive dyskinesia or other neurological concerns. They peaked around 2012, driven by submissions through legal workers. Most reports about metoclopramide described short-term use to prevent or treat nausea and vomiting. Concerns about acid-suppressive medications increased over time and spanned a wide spectrum of potential problems, including osteoporosis, worsening renal function, or cardiac events.

Conclusion

Despite biasing factors, such as pending legal action, the voluntary repository of adverse events provides insight into current medical practice and its associated risk. Knowing about common and uncommon, but potentially serious risks may enable patients and providers to decide on effective and safe management strategies.

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Molecular and clinical delineation of 2p15p16.1 microdeletion syndrome

Interstitial 2p15p16.1 microdeletion is a rare chromosomal syndrome previously reported in 33 patients. It is characterized by intellectual disability, developmental delay, autism spectrum disorders, microcephaly, short stature, dysmorphic features, and multiple congenital organ defects. It is defined as a contiguous gene syndrome and two critical regions have been proposed at 2p15 and 2p16.1 loci. Nevertheless, patients with deletion of both critical regions shared similar features of the phenotype and the correlation genotype–phenotype is still unclear. We review all published cases and describe three additional patients, to define the phenotype–genotype correlation more precisely. We reported on two patients including the first prenatal case described so far, carrying a 2p15 deletion affecting two genes: XPO1 and part of USP34. Both patients shared similar features including facial dysmorphism and cerebral abnormalities. We considered the genes involved in the deleted segment to further understand the abnormal phenotype. The third case we described here was a 4-year-old boy with a heterozygous de novo 427 kb deletion encompassing BCL11A and PAPOLG at 2p16.1. He displayed speech delay, autistic traits, and motor stereotypies associated with brain structure abnormalities. We discuss the contribution of the genes included in the deletion to the abnormal phenotype. Our three new patients compared to previous cases, highlighted that despite two critical regions, both distal deletion at 2p16.1 and proximal deletion at 2p15 are associated with phenotypes that are very close to each other. Finally, we also discuss the genetic counseling of this microdeletion syndrome particularly in the course of prenatal diagnosis.

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Auditory and otologic profile of Alström syndrome: Comprehensive single center data on 38 patients

Alström syndrome (AS) is a rare autosomal recessive ciliopathy caused by mutations in the ALMS1 gene. Hallmark characteristics include childhood onset of severe retinal degeneration, sensorineural hearing loss, obesity, insulin-resistant diabetes, and cardiomyopathy. Here we comprehensively characterize the auditory and otologic manifestations in a prospective case series of 38 individuals, aged 1.7–37.9 years, with genetically confirmed AS. Hearing loss was preceded by retinal dystrophy in all cases, and had an average age of detection of 7.45 years (range 1.5–15). Audiometric assessments showed mean pure tone averages (0.5, 1, 2, 4 kHz) of 48.6 and 47.5 dB HL in the right and left ears, respectively. Hearing was within normal limits for only 8/74 ears (11%). For the 66 ears with hearing loss, the degree was mild (12%), moderate (54%), or severe (8%). Type of hearing loss was predominantly sensorineural (77%), while three ears had mixed loss, no ears had conductive loss, and type of hearing loss was indeterminate for the remaining 12 ears. Serial audiograms available for 33 patients showed hearing loss progression of approximately 10–15 dB/decade. Our data show that hearing loss associated with AS begins in childhood and is a predominantly symmetric, sensory hearing loss that may progress to a severe degree. Absent otoacoustic emissions, intact speech discrimination, and disproportionately normal auditory brainstem responses suggest an outer hair cell site of lesion. These findings indicate that individuals with AS would benefit from sound amplification and if necessary, cochlear implantation.

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The influence of sleep disordered breathing in REM sleep behavior disorder

Because both REM sleep behavior disorder (RBD) and Obstructive Sleep Apnea (OSA) can present with similar symptoms, it is important to understand the influence of OSA in the clinical manifestations of RBD and whether RBD modulates OSA severity. Our objectives were to compare: 1. the intensity of non-motor symptoms between RBD patients with (RBD-OSA) and without OSA (RBD-non-OSA), and 2. polysomnographic features between RBD-OSA and OSA without RBD (OSA-non-RBD) patients.

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Overlap Parasomnia Disorder in a case of Creutzfeldt-Jakob Disease

Creutzfeldt-Jakob Disease (CJD), the most common human prion disease, is a rare form of adult fatal dementia caused by widespread brain accumulation of abnormal isoform (PrPSc) of the host encoded cellular prion protein (PrPC)1,2. CJD is characterized by rapidly progressive dementia, associated with numerous neurological symptoms and signs, including referred insomnia and hypersomnia3. So far, few video-polysomnographic data are available in CJD, documenting a reduction of SWS and REM sleep, and loss of sleep-wake cyclic organization4,5.

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The elderly and direct antiviral agents: constraint or challenge?

direct antiviral agents (DAAs) for chronic hepatitis C showed great effectiveness and good safety profile. So far, few data are available about their use in elderly subjects.

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Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study

Future Oncology Ahead of Print.


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Overexpression of the human antigen R suppresses the immediate paradoxical proliferation of melanoma cell subpopulations in response to suboptimal BRAF inhibition

Abstract

Tumor plasticity and the heterogeneous response of melanoma cells to targeted therapies are major limits for the long-term efficacy of this line of therapy. Targeting tumor plasticity is theoretically possible through the modulation of the expression of RNA-binding proteins which can affect many different compensatory mechanisms of the adaptive response of malignant cells to targeted therapies. Human antigen R (HuR) is a modulator of gene expression and a transacting factor in the mRNA-processing machinery used in the cell stress response, and is a potential target for reducing tumor plasticity. In this experiment, we exploit the inherent heterogeneous response of the A375 melanoma line to suboptimal BRAF inhibition as a model of immediate adaptive response. We first observe that HuR overexpression can prevent the heterogeneous response and thus the immediate paradoxical proliferation induced by low-doses vemurafenib treatment. We then use single-cell mass cytometry to characterize subpopulations, including those that paradoxically proliferate, based on their proliferation rate and the expression patterns of markers involved in the reversible adaptive resistance to BRAF inhibition and/or recognized as HuR targets involved in cell cycle regulation. Under suboptimal BRAF inhibition, HuR overexpression affects these subpopulations and their expression pattern with contrasting responses depending on their proliferation rate: faster-proliferating vemurafenib-sensitive or -resistant subpopulations showed higher death tendency and reduced size, and slower-proliferating subpopulations showed an attenuated resistant expression response and their paradoxical proliferation was inhibited. These observations pave the way to new therapeutic strategies for preventing the heterogeneous response of tumors to targeted therapies.

Tumor heterogeneous response of melanoma cells to targeted therapies is limiting their efficacy. In this study, using single-cell mass cytometry, we were able to track within the heterogeneous response of a melanoma BRAFV600-sensitive cell line, the paradoxically proliferating subsets of cells that emerge as an immediate response to suboptimal BRAF inhibition. Moreover, we were able to show that the overexpression of the human antigen R overcomes such immediate heterogeneous response. This study initiates a new avenue to prevent the occurrence of adaptive resistance to targeted therapies.

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Is long-term postoperative monitoring of microsurgical flaps still necessary?

Autologous microsurgical flap reconstruction has become commonplace in most plastic surgery units, and the success rates of this procedure have markedly increased over recent years. However, the possibility of flap failure still needs to be considered. A review of the literature reveals that the critical period for flap-threatening complications is the first 24-to-48 postoperative hours; however, the window for the onset of these complications remains open for up to 7 days postoperatively. Here, we focus on the timing of flap complications, aiming to elucidate the time period over which meticulous flap monitoring can still contribute positively to flap salvage rates.

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Expression of MICU1 after experimental focal cerebral ischemia in adult rats

Abstract

Background

Mitochondrial Ca²⁺ uptake is a pivotal pathophysiological process for neuronal survival when subjected to ischemic insult. Mitochondrial calcium uptake 1 (MICU1) has been demonstrated as a key regulator of the mitochondrial calcium uniporter (MCU), identified as a tetrameric highly specific channel that modulates mitochondrial Ca²+ uptake.

Methods

Adult male Sprague–Dawley (SD) rats underwent middle cerebral artery occlusion (MCAO) to create the standard focal cerebral ischemia model. The permanent MCAO approach utilized the intraluminal approach. Neurological examination, and subsequent histological characterization of cerebral infarcts using triphenyltetrazolium chloride staining, as well as Western blot, immunohistochemical staining, and real-time quantitative polymerase chain reaction assays were employed to assess the functional effects of MICU1 and its expression in the brain.

Results

Animals exposed to MCAO displayed the typical neurological deficit accompanied by cortical and subcortical infarction at 72 h post-stroke. The expression of MICU1, with co-localization with neurons, was detected at different time points (6 h and 12 h) after ischemic damage. Altogether, these observations revealed an up-regulation of MICU1 expression in the early stages of cerebral ischemia.

Conclusion

The results demonstrated that MICU1 was upregulated in neurons at the acute phase of ischemic stroke. Because MICU1 has been previously shown to participate in mitochondrial Ca²⁺ uptake mediated by MCU, our study further implicates the involvement of MICU1 in calcium overload-induced cell death which is closely associated with stroke.

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Ten-year survival after endoscopic stenting as a bridge to surgery in obstructing colon cancer

Self-expandable metallic stents are increasingly used in the treatment of obstructing colorectal cancer (CRC). Although endoscopic colonic stenting is widely accepted in palliation, disagreement exists about its role in a curative setting. This study aims to describe long-term survival data in a large patient group, treated with colonic stenting as a bridge to surgery (BTS) for CRC.

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Electromagnetic-guided placement of nasoduodenal feeding tubes versus endoscopic placement: a randomized, multicenter trial

Electromagnetic-guided placement (EMP) of a nasoduodenal feeding tube by trained nurses is an attractive alternative to esophagogastroduodenoscopy guided placement (EGDP). We aimed to compare EMP and EGDP in outpatients, ward patients, and critically ill patients with normal upper GI anatomy.

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Effect of 1- or 2-level posterior lumbar interbody fusion on global sagittal balance

Sagittal imbalance is associated with poor clinical outcomes in patients with degenerative lumbar disease. However, there is no consensus on the impact of posterior lumbar interbody fusion (PLIF) on local and global sagittal balance.

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The 150 most important questions in cancer research and clinical oncology series: questions 31–39

To accelerate our endeavors to overcome cancer, Chinese Journal of Cancer has launched a program of publishing 150 most important questions in cancer research and clinical oncology. In this article, 9 more questi...

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Palonosetron compared with ondansetron in pediatric cancer patients: multicycle analysis of a randomized Phase III study

Future Oncology Ahead of Print.


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Fast Ambulance Responding

S m a r t Nation....I will N O T post anny information that could save an American life, -before the Orange Dildo is DEAD !ExEMTNor

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Fast Ambulance Responding

S m a r t Nation....I will N O T post anny information that could save an American life, -before the Orange Dildo is DEAD !ExEMTNor

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Michael Moore in Norway

The future...

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Influence of broadleaf forest vegetation on atmospheric deposition of airborne radionuclides

Publication date: October 2017
Source:Journal of Environmental Radioactivity, Volume 177
Author(s): Miodrag Krmar, Dragan Radnović, Jan Hansman, Predrag Repić
The activities of airborne radionuclides ⁷Be and unsupported ²¹⁰Pb (²¹⁰Pbus) were measured in moss samples taken from 17 different locations. The objective was to estimate the influence of the broadleaf forest vegetation on atmospheric deposition of airborne radionuclides attached to aerosols. Two moss samples were collected at each location: within the forest stand (inside the area of the tree canopy projection) and within forest openings (outside the area of the tree canopy projection). Samples were taken in the spring season, before the leaves of trees came forth and in the autumn season, right before fall defoliation. A measurement indicates an absence of variation in ²¹⁰Pbus concentration, however spring/autumn ratios of ⁷Be concentrations in mosses showed the expected seasonal difference in ⁷Be deposition. It was also noted that atmospheric deposition of ⁷Be at the forest openings was about two times higher than deposition in the forest. Using very simplified models, these measurements can be used to get estimation at how long ⁷Be and aerosols can reside on the leaves before precipitation eventually wash it to the ground mosses. It was estimated that the mean residence time of aerosols in the leaves was up to 50 days.



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Aberrant gene promoter methylation of E - cadherin , p16 INK4a , p14 ARF , and MGMT in Epstein–Barr virus-associated oral squamous cell carcinomas

Abstract

The etiology of oral carcinogenesis appears to be multifactorial. There is emerging evidence of the presence of Epstein–Barr virus (EBV) in epithelial oral squamous cell carcinoma (OSCC), but an association of EBV with oral carcinogenesis has not yet been established. Although epigenetic alterations, such as aberrant DNA methylation, are known to contribute to the pathogenesis of oral cancer, the relationship of such alterations with EBV infection is little known. This study aimed to investigate the association between EBV infection and promoter methylation patterns of tumor-associated genes in OSCC tissues. A total of 165 of formalin-fixed paraffin-embedded OSCC tissues were studied (68 of EBV positive and 97 of EBV negative). The promoter methylation patterns were investigated for four tumor-associated genes, E-cadherin, p16 ^INK4a , p14 ^ARF , and MGMT, by using methylation-specific polymerase chain reaction (MSP). The frequencies of gene promoter hypermethylation in all cases were 47.3% for E-cadherin, 92.7% for p16 ^INK4a , 74.5% for p14 ^ARF , and 35.8% for MGMT. Interestingly, most of the analyzed gene promoters were more frequently hypermethylated in EBV-positive than EBV-negative cases, in particular the E-cadherin (56/22) and MGMT (38/21) gene promoters (p < 0.05). Concomitantly, hypermethylation of multiple gene promoters (≥3) was encountered more frequently in EBV-positive samples. Hypermethylation of the E-cadherin promoter associated with EBV was more frequently observed in moderately and poorly differentiated OSCC tissues. These results indicate that epigenetic changes frequently occur in OSCCs and may partly be induced by EBV infection, therefore, EBV may involve in development and progression of the OSCCs.

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Predictive validity of the GOSLON Yardstick index in patients with unilateral cleft lip and palate: A systematic review

by Cindy Buj-Acosta, Vanessa Paredes-Gallardo, José María Montiel-Company, Alberto Albaladejo, Carlos Bellot-Arcís

Among the various indices developed for measuring the results of treatment in patients born with unilateral cleft lip and palate (UCLP), the GOSLON Yardstick index is the most widely used to assess the efficacy of treatment and treatment outcomes, which in UCLP cases are closely linked to jaw growth. The aim of this study was to conduct a systematic review to validate the predictability of growth using the GOSLON Yardstick in patients born with UCLP. A systematic literature review was conducted in four Internet databases: Medline, Cochrane Library, Scopus and Embase, complemented by a manual search and a further search in the databases of the leading journals that focus on this topic. An electronic search was also conducted among grey literature. The search identified a total of 131 articles. Duplicated articles were excluded and after reading titles and abstracts, any articles not related to the research objective were excluded, leaving a total of 21 texts. After reading the complete text, only three articles fulfilled the inclusion criteria. The results showed a predictive validity of between 42.2% and 64.7%, which points to a lack of evidence in the literature for the predictive validity of the GOSLON Yardstick index used in children born with UCLP.

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The elderly and direct antiviral agents: constraint or challenge?

direct antiviral agents (DAAs) for chronic hepatitis C showed great effectiveness and good safety profile. So far, few data are available about their use in elderly subjects.

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Comparative proteomic profiling of the serum differentiates pancreatic cancer from chronic pancreatitis

Abstract

Finland ranks sixth among the countries having highest incidence rate of pancreatic cancer with mortality roughly equaling incidence. The average age of diagnosis for pancreatic cancer is 69 years in Nordic males, whereas the average age of diagnosis of chronic pancreatitis is 40–50 years, however, many cases overlap in age. By radiology, the evaluation of a pancreatic mass, that is, the differential diagnosis between chronic pancreatitis and pancreatic cancer is often difficult. Preoperative needle biopsies are difficult to obtain and are demanding to interpret. New blood based biomarkers are needed. The accuracy of the only established biomarker for pancreatic cancer, CA 19-9 is rather poor in differentiating between benign and malignant mass of the pancreas. In this study, we have performed mass spectrometry analysis (High Definition MS^E) of serum samples from patients with chronic pancreatitis (13) and pancreatic cancer (22). We have quantified 291 proteins and performed detailed statistical analysis such as principal component analysis, orthogonal partial least square discriminant analysis and receiver operating curve analysis. The proteomic signature of chronic pancreatitis versus pancreatic cancer samples was able to separate the two groups by multiple statistical techniques. Some of the enriched pathways in the proteomic dataset were LXR/RXR activation, complement and coagulation systems and inflammatory response. We propose that multiple high-confidence biomarker candidates in our pilot study including Inter-alpha-trypsin inhibitor heavy chain H2 (Area under the curve, AUC: 0.947), protein AMBP (AUC: 0.951) and prothrombin (AUC: 0.917), which should be further evaluated in larger patient series as potential new biomarkers for differential diagnosis.

Serum proteomics has the potential to find the candidate biomarkers for various types of cancers enabling differential diagnosis. We have performed HDMSE of serum samples from chronic pancreatitis and pancreatic cancer patients and quantified hundreds of proteins. Exhaustive statistical analyses such as OPLS-DA, PCA, ROC curve analyses and multiple pathway analyses were performed which provided dysregulated pathways in these diseases and high-confidence potential biomarker candidates were proposed.

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Dentigerous cysts associated with impacted third molars in adults after decompression: a prospective survey of reduction in volume using computerised analysis of cone-beam computed tomographic images

We prospectively investigated in adults the decompression of dentigerous cysts associated with impacted third molars at high risk of iatrogenic damage during extraction. The computerised calculated volumetric postoperative reductions measured by cone-beam computed tomography at four and eight months were correlated with the duration of treatment, initial volume, and patient’s age. We prospectively monitored 14 adult patients with 14 dentigerous cysts that were associated with impacted third molars, for eight months after decompression.

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Neocondylar formation after resection of the mandible and reconstruction with a vascularised iliac crest free flap: rare case

Tumours in the mandible often necessitate the removal of both mandibular and condylar bone. A free vascularised bone flap is a common choice for reconstruction, but it is rare for adults to form a new condyle after it. We describe a patient in whom a new condyle did form after reconstruction with a vascularised iliac crest free flap.

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Setting up a successful special interest study group: five-year reflection

Continuing medical education (CME), which helps clinicians maintain competence and learn about new and developing areas of their specialty, is required by the General Medical Council (GMC) to meet the standard for good medical practice. We describe our experience of establishing an orthognathic study group, and identify factors relevant to its success.

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Anchors for sutures to fix pedicled flaps to the floor of the mouth in reconstructions for cancer

We have already described the use of minisized Mitek® suture anchors (Depuy Mitek Surgical Products, Inc. Raynham, Mass, USA) to fix free flaps in the reconstructions of oral and oropharyngeal defects after resections for cancer.1,2 The anchors are available in different sizes: micro, mini, GII, and super. The minisized ones require that a hole 1cm deep be placed in the recipient bone, but the thickness and quality of the bone may be insufficient to fulfill this requirement. Recently, we tested the microsized anchors for fixing regional pedicled flaps, which are typically used in the reconstruction of the floor of the mouth when the tumour has spared both the mylohyoid muscle and the mandible, and when harvesting nasolabial,3 intraoral facial artery musculomucosal,4 or submental flaps.

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Intraoperative Ketamine Does Not Cut Postop Delirium, Pain

Guidelines should revisit common practice of giving intraoperative ketamine to surgery patients to reduce postoperative pain and delirium, study suggests.
Medscape Medical News

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Phosphaturic mesenchymal tumor of the nasal cavity and paranasal sinuses: A clinical curiosity presenting a diagnostic challenge

Phosphaturic mesenchymal tumor (PMT) is a rare mesenchymal neoplasm associated with tumor-induced osteomalacia (TIO) and elevated serum FGF-23. Common in extremities, PMT rarely occurs in sinonasal region. We report a series of sinonasal PMT diagnosed at our institute over a 6-year period.Six cases of sinonasal PMT were identified during this period, of which five presented with features of TIO. Median age of patients was 45.5 years. All six tumors were composed of stellate to spindled cells, with prominent staghorn vasculature in four cases.

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Preclinical efficacy and molecular mechanism of targeting CDK7-dependent transcriptional addiction in ovarian cancer

Ovarian cancer remains a significant cause of gynecological cancer mortality and novel therapeutic strategies are urgently needed in clinic as new treatment options. We previously showed that BET bromodomain inhibitors displayed promising efficacy for the treatment of epithelial ovarian cancer by downregulating pivot transcription factors. However, the potential anti-tumor activities and molecular mechanisms of other epigenetic or transcriptional therapies have not been systematically determined. Here, by performing an unbiased high-throughput drug screen to identify candidate compounds with antineoplastic effects, we identified THZ1, a recently developed covalent CDK7 inhibitor, as a new transcription-targeting compound that exerted broad cytotoxicity against ovarian tumors. Mechanistically, CDK7 represented a previously unappreciated actionable vulnerability in ovarian cancer and CDK7 inhibition led to a pronounced disregulation of gene transcription, with a preferential repression of E2F-regulated genes and transcripts associated with super-enhancers. Our findings revealed the molecular underpinnings of THZ1 potency and established pharmaceutically targeting transcriptional addiction as a promising therapeutic strategy in aggressive ovarian cancer.

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Colony-stimulating factor 1 receptor blockade inhibits tumor growth by altering the polarization of tumor-associated macrophages in hepatocellular carcinoma

Colony-stimulating factor-1 (CSF-1) and its receptor, CSF-1R, regulate the differentiation and function of macrophages and play an important role in macrophage infiltration in the context of hepatocellular carcinoma (HCC). The therapeutic effects of CSF-1R blockade in HCC remain unclear. In this study, we found that CSF-1R blockade by PLX3397, a competitive inhibitor with high specificity for CSF-1R tyrosine kinase, significantly delayed tumor growth in mouse models. PLX3397 inhibited the proliferation of macrophages in vitro, but intratumoral macrophage infiltration was not decreased by PLX3397 in vivo. Gene expression profiling of tumor-associated macrophages (TAMs) showed that TAMs from the PLX3397-treated tumors were polarized toward an M1-like phenotype compared with those from vehicle-treated tumors. In addition, PLX3397 treatment increased CD8⁺ T-cell infiltration, whereas CD4⁺ T-cell infiltration was decreased. Further study revealed that tumor cell-derived CSF-2 protected TAMs from being depleted by PLX3397. In conclusion, CSF-1R blockade delayed tumor growth by shifting the polarization rather than the depletion of TAMs. CSF-1R blockade warrants further investigation in the treatment of HCC.

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Tumor-targeted nanoparticle delivery of HuR siRNA inhibits lung tumor growth in vitro and in vivo by disrupting the oncogenic activity of the RNA-binding protein HuR

Selective downregulation of the human antigen R (HuR) protein by siRNA may provide a powerful approach for treating lung cancer. To this end, we investigated the efficacy of transferrin receptor-targeted liposomal nanoparticle-based HuR siRNA (HuR-TfNP) therapy and compared to control siRNA (C)-TfNP therapy both, in vitro and in vivo using lung cancer models.In vitro studies showed HuR-TfNP but not C-TfNP efficiently downregulated HuR and HuR-regulated proteins in A549, and HCC827 lung cancer cells resulting in reduced cell viability, inhibition of cell migration and invasion, and induction of G1 cell-cycle arrest culminating in apoptosis. However, HuR-TfNP activity in normal MRC-9 lung fibroblasts was negligible. In vivo biodistribution study demonstrated that fluorescently labeled HuR-siRNA or ICG dye loaded TfNP localized in tumor tissues. Efficacy studies showed intratumoral or intravenous administration of HuR-TfNP significantly inhibited A549 (>55% inhibition) and HCC827 (>45% inhibition) subcutaneous tumor growth compared to C-TfNP. Furthermore, HuR-TfNP treatment reduced HuR, Ki67, and CD31 expression and increased caspase-9 and PARP cleavage and TUNEL positive staining indicative of apoptotic cell death in tumor tissues compared to C-TfNP treatment. The antitumor activity of HuR-TfNP was also observed in an A549-luc lung metastatic model, as significantly fewer tumor nodules (9.5±3.1; p<0.001; 88% inhibition) were observed in HuR-TfNP-treated group compared with the C-TfNP-treated group (77.7±20.1). Significant reduction in HuR, Ki67, and CD31 expression was also observed in the tumor tissues of HuR-TfNP-treatment compared to C-TfNP treatment.Our findings highlight HuR-TfNP as a promising nano-therapeutic system for lung cancer treatment.

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Cognitive reserve is a resilience factor for cognitive dysfunction in hepatic encephalopathy

Abstract

Cognitive Reserve (CR) modulates symptoms of brain disease. The aim of this study was: to evaluate the effect of CR on cognition in cirrhosis and on the mismatch between cognitive and neurophysiologic assessment of hepatic encephalopathy (HE). Eighty-two outpatient patients with cirrhosis without overt HE were studied [73% males; age: 62 (54–68) (median, interq. range) yrs.; education: 8 (6–13) yrs.]. The Psychometric Hepatic Encephalopathy Score (PHES) was used as cognitive measure of HE. The spectral analysis of the electroencephalogram (EEG) was used as neurophysiologic measure of HE. The CR was assessed by the CR Index (CRI), which was measured by the CRI questionnaire (CRIq) (http://cri.psy.unipd.it). The PHES was altered in 28% of patients and the EEG in 41%. Altered PHES was related to the severity of cirrhosis as assessed by Child-Pugh classification (R = 0.31, p < 0.005). Patients with maintained PHES had higher CRI than those with altered PHES (CRI = 100 ± 20 vs. 88 ± 12 vs., p < 0.01), but not the ones with normal EEG compared to those with abnormal EEG (CRI = 96 ± 17 vs. 98 ± 17 vs. p: n.s.).The PHES, but not the EEG, was found to be related to the CRI (r = 0.35, p < 0.01). The mismatch between cognitive and neurophysiologic evaluation of non-overt HE (the ratio between PHES and the mean dominant frequency -MDF- of the EEG i.e., cognitive performance normalized by EEG speed) was found to be correlated to the CRI (r = 0.36, p < 0.005). CR is a resilience factor for cognitive dysfunction in cirrhosis, and is easily measurable by CRIq.

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Gallic acid and p -coumaric acid attenuate type 2 diabetes-induced neurodegeneration in rats

Abstract

The brain of diabetics revealed deterioration in many regions, especially the hippocampus. Hence, the present study aimed to evaluate the effects of gallic acid and p-coumaric acid against the hippocampal neurodegeneration in type 2 diabetic rats. Adult male albino rats were randomly allocated into four groups: Group 1 served as control ones and others were induced with diabetes. Group 2 considered as diabetic, and groups 3 and 4 were further orally treated with gallic acid (20 mg/kg b.wt./day) and p-coumaric acid (40 mg/kg b.wt./day) for six weeks. Diabetic rats revealed significant elevation in the levels of serum glucose, blood glycosylated hemoglobin and serum tumor necrosis factor-α, while the level of serum insulin was significantly declined. Furthermore, the brain of diabetic rats showed a marked increase in oxidative stress and a decrease of antioxidant parameters as well as upregulation the protein expression of Bax and downregulation the protein expression of Bcl-2 in the hippocampus. Treatment of diabetic rats with gallic acid and p-coumaric acid significantly ameliorated glucose tolerance, diminished the brain oxidative stress and improved antioxidant status, declined inflammation and inhibited apoptosis in the hippocampus. The overall results suggested that gallic acid and p-coumaric acid may inhibit hippocampal neurodegeneration via their potent antioxidant, anti-inflammatory and anti-apoptotic properties. Therefore, both compounds can be recommended as hopeful adjuvant agents against brain neurodegeneration in diabetics.

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Experimental Intermittent Ischemia Augments Exercise-Induced Inflammatory Cytokine Production

Acute exercise-induced inflammation is implicated in mediating the beneficial adaptations to regular exercise. Evidence suggests that reduced oxygen and/or blood flow to contracting muscle alters cytokine appearance. However, the acute inflammatory responses to hypoxic/ischemic exercise have been documented with inconsistent results and may not accurately reflect the ischemia produced during exercise in patients with ischemic cardiovascular diseases. Therefore, we determined the extent to which local inflammation is involved in the response to ischemic exercise. Fourteen healthy males performed unilateral isometric forearm contractions for 30 minutes with and without experimental ischemia. Blood was drawn at baseline, 5 and 10 minutes into exercise, at the end of exercise, and 30, 60, and 120 minutes after exercise. Oxygen saturation levels, as measured by near-infrared spectroscopy, were reduced by 10% and 41% during non-ischemic and ischemic exercise, respectively. Non-ischemic exercise did not affect cytokine values. Ischemia enhanced concentrations of basic fibroblast growth factor, interleukin (IL)-6, IL-10, tumor necrosis factor-alpha, and vascular endothelial growth factor during exercise, but IL-8 was not influenced by ischemic exercise. In conclusion, the present study demonstrates that ischemic, small muscle endurance exercise elicits local inflammatory cytokine production, compared to non-ischemic exercise.

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Beta-1 versus beta-2 adrenergic control of coronary blood flow during isometric handgrip exercise in humans

During exercise, β-adrenergic receptors are activated throughout the body. In healthy humans, the net effect of β-adrenergic stimulation is an increase in coronary blood flow. However, the role of vascular β1 versus β2 receptors in coronary exercise hyperemia is not clear. In this study we simultaneously measured noninvasive indices of myocardial oxygen supply (i.e., blood velocity in the left anterior descending coronary artery; Doppler echocardiography) and demand (i.e., rate pressure product; RPP = heart rate x systolic blood pressure) and tested the hypothesis that β1 blockade with esmolol improves coronary exercise hyperemia compared to nonselective β-blockade with propranolol. Eight healthy young men received intravenous infusions of esmolol, propranolol, and saline on three separate days in a single-blind, randomized, crossover design. During each infusion, subjects performed isometric handgrip exercise until fatigue. Blood pressure, heart rate, and coronary blood velocity (CBV) were measured continuously and RPP was calculated. Changes in parameters from baseline were compared with paired t-tests. Esmolol (=3296 ± 1204) and propranolol (=2997 ± 699) caused similar reductions in peak RPP compared to saline (=5384 ± 1865). In support of our hypothesis, CBV with esmolol was significantly greater than with propranolol (7.3 ± 2.4 versus 4.5 ± 1.6 cm/sec, P = 0.002). This effect was also evident when normalizing CBV to RPP. In summary, not only does selective β1 blockade reduce myocardial oxygen demand during exercise but it also unveils β2 receptor mediated coronary exercise hyperemia.

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Reflex cardiorespiratory events from esophageal origin are heightened by preterm birth

The involvement of gastroesophageal refluxes in cardiorespiratory events of preterm infants remains controversial. While a few studies in full term newborn animals have shown that stimulation of esophageal receptors leads to cardiorespiratory reflexes, the latter remain largely unknown, especially after premature birth. The present study aimed to i) characterize the cardiorespiratory reflexes originating from esophageal receptors in newborn lambs, and ii) test the hypotheses that preterm birth enhances reflex cardiorespiratory inhibition and that C-fibers are involved in these reflexes. Eight full-term lambs and ten lambs born 14 days prematurely were studied. Following surgical instrumentation, a six-hour polysomnography was performed without sedation to record electrocardiogram, respiratory movements, arterial pressure, laryngeal constrictor muscle activity, state of alertness and hemoglobin oxygen saturation. Five esophageal stimulations of the upper and/or lower esophagus, including rapid balloon inflation and/or HCl injection, were performed in random order. A second recording was performed in full-term lambs 24h later, after C-fiber blockade by capsaicin. Results confirmed that esophageal stimulations induced inhibitory cardiorespiratory reflexes combined with protective mechanisms including laryngeal closure, swallowing, coughing, increased arterial pressure and arousal. Preterm birth heightened cardiorespiratory inhibition. The strongest cardiorespiratory inhibition was observed following simultaneous stimulation of the lower and upper esophagus. Finally, cardiorespiratory inhibition was decreased after C-fiber blockade. In conclusion, esophageal stimulation induces inhibitory cardiorespiratory reflexes, which are partly mediated by C-fibers and more pronounced in preterm lambs. Clinical relevance of these findings requires further studies, especially in conditions associated with increased cardiorespiratory events, e.g., neonatal infection.

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Erythrocyte Purinergic Signaling Components Underlie Hypoxia Adaptation

Erythrocytes are vital to human adaptation under hypoxic conditions because of their abundance in number and irreplaceable function of delivering oxygen (O₂). However, although multiple large-scale altitude studies investigating the overall coordination of the human body for hypoxia adaptation have been conducted, detailed research with a focus on erythrocytes was missing due to lack of proper techniques. The recently maturing metabolomics profiling technology appears to be the answer to this limitation. Metabolomics profiling provides unbiased high-throughput screening data that reveal the overall metabolic status of erythrocytes. Recent studies have exploited this new technology and provided novel insight into erythrocyte physiology and pathology. In particular, a series of studies focusing on erythrocyte purinergic signaling have reported that adenosine signaling, coupled with 5' AMP-activated protein kinase (AMPK) and the production of erythrocyte-enriched bioactive signaling lipid sphingosine 1-phosphate, regulate erythrocyte glucose metabolism for more O₂ delivery. Moreover, an adenosine-dependent "Erythrocyte Hypoxic Memory" was discovered which provides an explanation for fast acclimation upon re-ascent. These findings not only shed new light on our understanding of erythrocyte function and hypoxia adaptation but also offer a myriad of novel therapeutic possibilities to counteract various hypoxic conditions.

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Neuromuscular electrical stimulation improves skeletal muscle regeneration through satellite cell fusion with myofibers in healthy elderly subjects

The aim was to determine whether neuromuscular electrical stimulation (NMES) affects skeletal muscle regeneration through a reduction of oxidative status in satellite cells of healthy elderly subjects. Satellite cells from the Vastus lateralis skeletal muscle of 12 healthy elderly subjects before and after 8 weeks of NMES were allowed to proliferate to provide myogenic populations of adult stem cells (myogenic precursor cells; MPCs). These MPCs were then investigated in terms of their proliferation, their basal cytoplasmic free Ca²⁺ concentrations, and their expression of myogenic regulatory factors (PAX3, PAX7, MYF5, MYOD, MYOG) and microRNAs (miR-1, miR-133a/b, miR-206). The oxidative status of these MPCs was evaluated through superoxide anion production and superoxide dismutase and glutathione peroxidase activities. On dissected single skeletal myofibers, the nuclei were counted to determine the myonuclear density, the fiber phenotype, cross sectional area and tension developed. The MPCs obtained after NMES showed increased proliferation rates along with increased cytoplasmic free Ca²⁺ concentrations and gene expression of MYOD and MYOG on MPCs. The muscle-specific miR-1, miR133a/b, miR-206 were up-regulated. This NMES significantly reduced superoxide anion production, along with a trend to reduction of superoxide dismutase activity. The NMES-dependent stimulation of muscle regeneration enhanced satellite cells fusion with mature skeletal fibers. NMES improved the regenerative capacity of skeletal muscle in elderly subjects. Accordingly, the skeletal muscle strength and mobility of NMES-stimulated elderly significantly improved. NMES may thus be further considered for clinical or ageing populations.

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UBC-Nepal Expedition: Markedly lower cerebral blood flow in high altitude Sherpa children compared to children residing at sea-level

Developmental cerebral hemodynamic adaptations to chronic high altitude exposure, such as in the Sherpa population, are largely unknown. To examine hemodynamic adaptations in the developing human brain, we assessed common carotid (CCA), internal carotid (ICA) and vertebral artery (VA) flow and middle cerebral artery (MCA) velocity in 25 (9.6±1.0 y, 129±9 cm, 27±8 kg, 14 girls) Sherpa children (3800m, Nepal) and 25 (9.9±0.7 y, 143±7 cm, 34±6 kg, 14 girls) age-matched sea-level children (344m, Canada) during supine rest. Resting gas exchange, blood pressure, oxygen saturation and heart rate were assessed. Despite comparable age, height and weight were lower (both P<0.01) in Sherpa compared to sea-level children. Mean arterial pressure, heart rate and ventilation were similar, whereas oxygen saturation (95±2 vs. 99±1%, P<0.01) and end-tidal PCO₂ (24±3 vs 36±3 mmHg, P<0.01) were lower in Sherpa children. Global cerebral blood flow was ~30% lower in Sherpa compared to sea-level children. This was reflected in a lower ICA flow (283±108 vs. 333±56 ml/min, P=0.05), VA flow (78±26 vs 118±35 ml/min, P<0.05) and MCA velocity (72±14 vs 88±14 cm/s, P<0.01). CCA flow was similar between Sherpa and sea-level children (425±92 vs. 441±81 ml/min, P=0.52). Scaling flow and oxygen uptake for differences in vessel diameter and body size respectively, led to the same findings. A lower cerebral blood flow in Sherpa children may reflect specific cerebral hemodynamic adaptations to chronic hypoxia.

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Effect of calf-raise training on rapid force production and balance ability in elderly men

This study examined whether home-based, high-speed calf-raise training changes the rate of torque development during plantar flexion contractions and balance performance in elderly men. Thirty-four healthy elderly men (73 ± 5 yr) were randomly assigned to a training or control group (n = 17 in each group). The subjects in the training group completed 8 weeks (3 times/week) of home-based bilateral calf-raise training using body mass. Before and after the intervention, rate of torque development during plantar flexion contractions and center of pressure displacement during single-leg standing were measured. Surface electromyographic amplitude of the triceps surae and tibialis anterior during the strength and single-leg standing were measured. Clinical magnitude-based inferences were used to interpret the training effect, with smallest worthwhile effect being assumed to be 0.2 of the baseline standard deviation. The peak rate of torque development increased 21% (90% confidence limits, ±19%) relative to control group, which was accompanied by corresponding changes of the medial gastrocnemius and soleus activations. The effect on center of pressure displacement was possibly trivial (0%; ±13%), whereas substantial reduction in the medial gastrocnemius (-19%; ±15%) and soleus (-25%; ±13%) activations during standing was observed. Our findings indicate that calf-raise training at home, performed without special equipment or venue, induces a substantial increase in the plantar flexors' rapid force generating capability and triceps surae activations. Although the training effect on standing balance performance was not substantial, observed changes in the triceps surae activations during standing are expected to contribute to future balance performance improvement.

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Comparison of the Vasodilatory Effects of Sodium Nitroprusside versus Nitroglycerin

The vasodilatory mechanism of Nitroglycerin (NTG) is similar to Sodium Nitroprusside (SNP) in regards to action on guanosine 3'5' monophosphate (cyclic GMP) via nitric oxide. However, it is unknown whether NTG can achieve the same magnitude of vasodilation in the forearm as SNP. Therefore, the purpose of the study was to evaluate the differences in forearm blood flow (FBF) and forearm vascular conductance (FVC) during escalating infusions of NTG versus SNP at similar concentration doses and rates. We measured FBF using venous occlusion plethysmography (VOP) and Doppler ultrasound in eight young, healthy participants (mean age = 28 ± 2 years) during four forearm volume (FAV) specific doses (0.25, 0.5, 1, 2 µg•100mL FAV^-1•min^-1) of SNP and NTG, infused via a brachial artery catheter. There was a significant difference in FVC of SNP versus NTG only at the higher doses as measured by VOP (14.9 ± 1.4 and 18.3 ± 1.5 versus 11.6 ± 1.2 and 12.5 ± 1.2 mL•dL FAV^-1•min^-1•100mmHg^-1). FVC as measured by Doppler Ultrasound unadjusted for FAV was significantly different at the lowest and the higher 2 doses of SNP as compared to NTG (202.1 ± 25.8, 329.4 ± 46.7 and 408 ± 63.5 versus 142.9 ± 22.4, 217.2 ± 18.8 and 247.5 ±18.2 mL•min^-1•100mmHg). SNP induces significantly higher vasodilatory actions as compared to NTG. However, NTG is comparable in eliciting equivalent vasodilator effects to SNP during low concentration doses when measured by VOP. Importantly, for forearm pharmacology studies, NTG can elicit marked endothelium independent forearm vasodilation.

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Edward F. Adolph Distinguished Lecture Exercise: Teaching myocytes new tricks

Endurance exercise training promotes numerous cellular adaptations in both cardiac myocytes and skeletal muscle fibers. For example, exercise training fosters changes in mitochondrial dynamics including increased mitochondrial biogenesis and accelerated mitochondrial turnover. Additionally, endurance exercise training alters the abundance of numerous cytosolic and mitochondrial proteins in both cardiac and skeletal muscle myocytes, resulting in a protective phenotype in the active fibers; this exercise-induced protection of cardiac and skeletal muscle fibers is often referred to as "exercise preconditioning." In this regard, as few as 3-5 consecutive days of endurance exercise training results in a preconditioned cardiac phenotype that is sheltered against ischemia-reperfusion induced injury. Similarly, endurance exercise training results in preconditioned skeletal muscle fibers that are resistant to a variety of stresses (e.g., heat stress, exercise-induced oxidative stress, and inactivity-induced atrophy). Many studies have probed the mechanisms responsible for exercise-induced preconditioning of both cardiac and skeletal muscle fibers; these studies are important because they provide an improved understanding of the biochemical mechanisms responsible for exercise-induced preconditioning, which has the potential to lead to innovative pharmacological therapies aimed at minimizing stress-induced injury to cardiac and skeletal muscle. This review summarizes the process of exercise-induced protection of both cardiac and skeletal muscle myocytes and the mechanisms responsible for these important adaptive responses.

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Regulation of blood volume in lowlanders exposed to high altitude

Humans ascending to high altitude (HA) experience a reduction in arterial oxyhemoglobin saturation and, as a result, arterial O₂ content (C_aO₂). As HA exposure extends, this reduction in C_aO₂ is counteracted by an increase in arterial hemoglobin concentration. Initially, hemoconcentration is exclusively related to a reduction in plasma volume (PV), whereas after several weeks a progressive expansion in total red blood cell volume (RCV) contributes, although often to a modest extent. Since the decrease in PV is more rapid and usually more pronounced than the expansion in RCV, at least during the first weeks of exposure, a reduction in circulating blood volume is common at HA. Although the regulation of hematological responses to HA has been investigated for decades, it remains incompletely understood. This is not only related to the large number of mechanisms that could be involved and the complexity of their interplay but also to the difficulty of conducting comprehensive experiments in the often secluded HA environment. In this review, we present our understanding of the kinetics, the mechanisms and the physiological relevance of the HA-induced reduction in PV and expansion in RCV.

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Effect of age, diet and tissue type on PCr response to creatine supplementation

Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet and tissue, but studies assessing this possibility are lacking. Therefore, we aimed to determine whether the PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly participated in this study. Participants were given placebo and subsequently creatine (0.3 g•kg^-1•day^-1) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy (³¹P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children (p<0.0003) and elderly (p<0.001), whereas the increase in omnivores did not reach statistical significant difference (p=0.3348). Elderly had greater PCr increases than children and omnivores (p<0.0001 for both), whereas children experienced greater PCr increases than omnivores (p=0.0022). In relation to diet, vegetarians (p<0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior than muscle PCr content (+10.3 to +27.6%; p<0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g•kg^-1•day^-1 for 7 days) may be affected by age, diet and tissue. While creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimise creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine.

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Fast Ambulance Responding

S m a r t Nation....I will N O T post anny information that could save an American life, -before the Orange Dildo is DEAD !ExEMTNor

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Michael Moore in Norway

The future...

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Importance of chewing, saliva, and swallowing function in patients with advanced oral cancer undergoing preoperative chemoradiotherapy: a prospective study of quality of life

The primary objective of this study was to investigate the quality of life (QOL) of patients with oral squamous cell carcinoma (OSCC) undergoing curative neoadjuvant chemoradiotherapy followed by radical tumour resection and simultaneous oral cavity reconstruction, using two validated questionnaires. A secondary objective was to assess clinical variables predicting post-treatment dysfunction in chewing, saliva, and swallowing. Thirty-five patients with locally advanced OSCC who underwent preoperative chemoradiotherapy were recruited prospectively.

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A longitudinal study of changes in psychosocial well-being during orthognathic treatment

The aim was to evaluate changes in the psychosocial well-being of orthognathic surgery patients (n=22) during treatment and to compare results with those of adults not requiring orthognathic treatment (n=22). Patient data were collected before treatment (T0), after the first orthodontic examination (T1), three times during treatment (T2–T4), and 1 year after surgery (T5). In this article, only data corresponding to patient stage T5 are reported for the control subjects. Participants filled in a structured diary and the modified version of the Secord and Jourard body image questionnaire, the Orthognathic Quality of Life Questionnaire, the Rosenberg Self-Esteem Scale, and the Acceptance and Action Questionnaire II.

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Is centrally induced alveolar bone loss in a large animal model preventable by peripheral hormone substitution?

Abstract

Objectives

Alveolar bone structures are mostly investigated in small animal models. The majority of these studies examined local influences on the alveolar bone, but only a few examined systemic influencing factors. The hypothalamic-pituitary axis is known to be essential for a vital bone balance. The aim of this study was to analyse the effects that selective hormone treatments have on alveolar bone structure and quality in a sheep model for alveolar bone loss, induced by hypothalamic-pituitary disconnection (HPD).

Methods

Thirty sheep were randomly selected into six groups of five each: control (C), ovariectomy—OVX (O), O + HPD (OH), OH with oestrogen treatment (OHE), OH with thyroxine (T4) treatment (OHT), and OH with a combined treatment of oestrogen and thyroxine (OHTE). After OVX and HPD procedures and an additional 9-month observation/treatment period, structural bone analyses of the mandible were performed by contact radiography, micro-CT, and static histomorphometry.

Results

The HPD procedure caused structural alveolar bone parameters to decrease significantly compared to controls (C). Treatment with oestrogen (OHE) was protective and bone structure was maintained at baseline levels. Thyroxine treatment (OHT) promoted significant bone loss, but the combined treatment (OHTE) improved bone structure and volume parameters even above baseline levels.

Conclusions

Alveolar bone homeostasis significantly underlies systemic regulatory systems. Centrally induced (HPD) bone loss can be prevented by combined peripheral treatment with oestrogen and thyroxine.

Clinical relevance

These results demonstrate the significance of a balanced hormonal regulatory system for steady bone remodelling and maintenance of healthy alveolar bone.

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The Art and Science of Lifelong Singing

As a short prelude to the lecture, let us listen to the world-renowned male vocal ensemble, Chanticleer, perform the choral work, “I have had singing”.1,2 The text of the work follows:The singing—There was so much singing then,and this was my pleasure, too.We all sang—the boys in the fields,the chapels were full of singing, always singing.Here I lie. I have had pleasure enough.I have had singing!

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Protective Strategies Against Dysphonia in Teachers: Preliminary Results Comparing Voice Amplification and 0.9% NaCl Nebulization

Publication date: Available online 31 May 2017
Source:Journal of Voice
Author(s): Maria Lúcia Vaz Masson, Tânia Maria de Araújo
ObjectiveThis study aimed to compare the effects of two protective strategies, voice amplification (VA) and 0.9% NaCl nebulization (NEB), on teachers' voice in the work setting.MethodsAn interventional evaluator-blind study was conducted, assigning 53 teachers from two public high schools to one of the two protective strategy groups (VA or NEB). Vocal function was assessed in a sound-treated booth before and after a 4-week period. Assessment included the severity of voice impairment (Consensus Auditory-Perceptual Evaluation of Voice [CAPE-V]), acoustic analysis of fundamental frequency (f0), sound pressure level (SPL), jitter, shimmer, glottal-to-noise excitation ratio (GNE), noise (VoxMetria), and the self-rated Screening Index for Voice Disorder (SIVD). Data were statistically analyzed using SPSS Statistics (version 22) with a significance level of P ≤ 0.05. Effect size was calculated using Cohen's d coefficient.ResultsThere were no statistical differences between groups at baseline in terms of age, sex, time of teaching, teaching workload, and voice outcomes, except for SPL. During postintervention between groups, NEB displayed lower SIVD scores (VA = 3; NEB = 0; P = 0.018) and VA had lower acoustic irregularity (VA = 3.19; NEB = 3.69; P = 0.027), with moderate to large effect size. Postintervention within-groups decreased CAPE-V for VA (pretest = 31.97; posttest = 28.24; P = 0.021) and SIVD for NEB (pretest = 3; posttest = 0; P = 0.001). SPL decreased in both groups, NEB decreased in men only, and VA decreased in both men and women. NEB increased f0 for female participants (P ≤ 0.001).ConclusionBoth VA and NEB may help mitigate dysphonia in different pathways, being potential interventions for protecting teachers' voices in the work setting. An ongoing study with a control group will further support these preliminary results.



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Is centrally induced alveolar bone loss in a large animal model preventable by peripheral hormone substitution?

Abstract

Objectives

Alveolar bone structures are mostly investigated in small animal models. The majority of these studies examined local influences on the alveolar bone, but only a few examined systemic influencing factors. The hypothalamic-pituitary axis is known to be essential for a vital bone balance. The aim of this study was to analyse the effects that selective hormone treatments have on alveolar bone structure and quality in a sheep model for alveolar bone loss, induced by hypothalamic-pituitary disconnection (HPD).

Methods

Thirty sheep were randomly selected into six groups of five each: control (C), ovariectomy—OVX (O), O + HPD (OH), OH with oestrogen treatment (OHE), OH with thyroxine (T4) treatment (OHT), and OH with a combined treatment of oestrogen and thyroxine (OHTE). After OVX and HPD procedures and an additional 9-month observation/treatment period, structural bone analyses of the mandible were performed by contact radiography, micro-CT, and static histomorphometry.

Results

The HPD procedure caused structural alveolar bone parameters to decrease significantly compared to controls (C). Treatment with oestrogen (OHE) was protective and bone structure was maintained at baseline levels. Thyroxine treatment (OHT) promoted significant bone loss, but the combined treatment (OHTE) improved bone structure and volume parameters even above baseline levels.

Conclusions

Alveolar bone homeostasis significantly underlies systemic regulatory systems. Centrally induced (HPD) bone loss can be prevented by combined peripheral treatment with oestrogen and thyroxine.

Clinical relevance

These results demonstrate the significance of a balanced hormonal regulatory system for steady bone remodelling and maintenance of healthy alveolar bone.

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Effectiveness of Natural Compounds on DNA Damage in Coris julis (Linneaus 1758) from a Polluted Marine Area

Abstract

The evaluation of DNA damage in aquatic organisms represents one of the most widely used biomarkers in the assessment and monitoring of marine pollution. Our previous research highlighted the presence of DNA damage in hepatic nuclei and blood cells of Coris julis specimens collected from Augusta harbor (Syracuse, Italy), a site highly polluted. In this work, we investigated on the ability of different natural compounds with antioxidant and immunostimulating properties, such as resveratrol (50 μM, 100 μM), amygdalin (100 μM, 200 μM), and Urtica dioica roots extract (50 and/or 100 μg/ml), in reducing DNA damage of C. julis. Blood cells were analyzed by atypical cellular comet assay. The results confirmed that Augusta specimens are the most damaged and showed that resveratrol, followed by amygdalin and U. dioica roots extract, drastically reduced DNA damage. This finding evidences the effectiveness of three natural compounds for DNA protection suggesting the possible use of feed enriched with antioxidant compounds in aquaculture practices for organisms damaged by natural and anthropic insults.

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Patterns of Care Related to Post-Operative Radiotherapy for Patients with Prostate Cancer among Canadian Radiation Oncologists and Urologists

Abstract

The American Society for Radiation Oncology (ASTRO) and American Urological Association (AUA) developed post-prostatectomy radiotherapy (RT) guidelines to aid patient counseling on adjuvant (ART) and salvage radiotherapy (SRT). Our study compared how aware and compliant Canadian radiation oncologists and urologists are to these guidelines. Our online survey was distributed through the Canadian Association of Radiation Oncology (CARO) and Canadian Urology Association (CUA) to radiation oncologists and urologists that treat prostate cancer. We used Wilcoxon rank-sum test and Chi-square test to compare radiation oncologists and urologists. P values for significant findings are reported. A total of 128 participants responded the survey, 52 radiation oncologists, and 76 urologists. The majority (82%) of radiation oncologists had read these guidelines, compared to only 49% of urologists (p < 0.001). Radiation oncologists were more likely to recommend ART >50% for adverse pathological findings post-radical prostatectomy compared to urologists (76 vs. 51%, p = 0.011). Urologists were more likely to monitor their patient’s PSA level post-prostatectomy compared to radiation oncologists (93 vs. 77%, p = 0.016). Post-thematic analysis of open-ended questions revealed that urologists rarely refer patients to radiation oncologists for ART, with radiation oncologists confirming that they rarely receive referrals. This study demonstrates the low compliance to ASTRO/AUA guidelines. While radiation oncologists were more aware and compliant to guidelines, urologists were significantly more likely to monitor their patient’s PSA. This study highlighted the need for better communication between urologists and radiation oncologists, especially in referrals for ART, to facilitate treatment delivery that is concordant with ASTRO/AUA guidelines.

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The role of oxidative stress in EBV lytic reactivation, radioresistance and the potential preventive and therapeutic implications

Abstract

Epstein-Barr virus (EBV) is an important cancer causing virus. Cancer associated with EBV account for approximately 1.5% of all cancers, and represent 1.8% of all cancer deaths worldwide. EBV reactivation plays an important role in the development of EBV-related diseases and is closely related with patients' survival and clinical stages of EBV-related cancers. The therapy regarding to EBV-related cancers is very urgent, especially in endemic areas. Generating oxidative stress is a critical mechanism by which host cells defend against infection by virus. In addition, ROS-mediated oxidative stress plays a significant but paradoxical role acting as a “double-edged sword” to regulate cellular response to radiation, which is the main therapy strategy for EBV-related cancers, especially nasopharyngeal carcinoma. Therefore, in this review we primarily discuss the possible interplay among the oxidative stress, EBV lytic reactivation and radioresistance. Understanding the role of oxidative stress in EBV lytic reactivation and radioresistance will assist in the development of effective strategies for prevention and treatment of EBV-related cancers. This article is protected by copyright. All rights reserved.

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