| Ventilation through an extraglottic tracheal tube: a technique for deep extubation and airway control |
Wed, 07 Jun 2017 05:57:03 +0000 |
| ,The parable of Buridan's ass |
| Wed, 07 Jun 2017 05:46:05 +0000 |
The mechanisms by which exendin-4 and selenium exert their antidiabetic actions are still unclear. Here, we investigated the effects of exendin-4 or selenium administration on the expression of glucagon-like peptide-1 receptor (GLP-1R), insulin receptor substrate-1 (IRS-1), and preproinsulin in the pancreas of diabetic rats. Diabetes was induced by streptozotocin administration. Diabetic rats were injected intraperitoneally with 0.03 μg exendin-4/kg body weight/daily or treated with 5 ppm selenium in drinking water for a period of 4 weeks. GLP-1R and IRS-1 levels were decreased while the level of preproinsulin messenger RNA (mRNA) was increased in the pancreas of diabetic untreated rats, as compared to that in control rats. Treatment of diabetic rats with exendin-4 increased protein and mRNA levels of GLP-1R, and IRS-1, and the mRNA level of preproinsulin in the pancreas, as compared to their levels in diabetic untreated rats. Selenium treatment of diabetic rats increased the pancreatic mRNA levels of GLP-1R, IRS-1, and preproinsulin. Exendin-4 or selenium treatment of diabetic rats also increased the numbers of pancreatic islets and GLP-1R molecules in the pancreas. Therefore, exendin-4 and selenium may exert their antidiabetic effects by increasing GLP-1R, IRS-1, and preproinsulin expression in the pancreas and by increasing the number of pancreatic islets.
Megalencephalic leukoencephalopathy with cysts (MLC) is a genetic infantile-onset disease characterized by macrocephaly and white matter edema due to loss of MLC1 function. Recessive mutations in either MLC1 or GLIALCAM cause the disease. MLC1 is involved in astrocytic volume regulation; GlialCAM ensures the correct membrane localization of MLC1. Their exact role in brain ion-water homeostasis is only partly defined. We characterized Glialcam-null mice for further studies.
We investigated the consequences of loss of GlialCAM in Glialcam-null mice and compared GlialCAM developmental expression in mice and men.
Glialcam-null mice had early-onset megalencephaly and increased brain water content. From 3 weeks, astrocytes were abnormal with swollen processes abutting blood vessels. Concomitantly, progressive white matter vacuolization developed due to intramyelinic edema. Glialcam-null astrocytes showed abolished expression of MLC1, reduced expression of the chloride channel ClC-2 and increased expression and redistribution of the water channel aquaporin4. Expression of other MLC1-interacting proteins and the volume regulated anion channel LRRC8A was unchanged. In mice, GlialCAM expression increased until 3 weeks and then stabilized. In humans, GlialCAM expression was highest in the first 3 years to then decrease and stabilize from approximately 5 years.
Glialcam-null mice replicate the early stages of the human disease with early-onset intramyelinic edema. The earliest change is astrocytic swelling, further substantiating that a defect in astrocytic volume regulation is the primary cellular defect in MLC. GlialCAM expression affects expression of MLC1, ClC-2 and aquaporin4, indicating that abnormal interplay between these proteins is a disease mechanism in megalencephalic leukoencephalopathy with cysts.
We present two natalizumab-treated multiple sclerosis patients who developed glioblastoma multiforme (GBM) with variable outcomes. One patient had an isocitrate dehydrogenase (IDH)-wildtype GBM with aggressive behavior, who declined treatment and died 13 weeks after symptoms onset. The other patient underwent resection of an IDH-mutant secondary GBM that arose from a previously diagnosed grade II astrocytoma. He is still alive 5 years after the diagnosis of GBM. JC virus was not detected in either case. Whether natalizumab played a role in the development of GBM in those patients deserves further investigation.
Current investigations of stomach function are based on small test meals that do not reliably induce symptoms and analysis techniques that rarely detect clinically relevant dysfunction. This study presents the reference intervals of the modular “Nottingham test meal” (NTM) for assessment of gastric function by gamma scintigraphy (GSc) in a representative population of healthy volunteers (HVs) stratified for age and sex.
The NTM comprises 400 mL liquid nutrient (0.75 kcal/mL) and an optional solid component (12 solid agar-beads (0 kcal). Filling and dyspeptic sensations were documented by 100 mm visual analogue scale (VAS). Gamma scintigraphy parameters that describe early and late phase Gastric emptying (GE) were calculated from validated models.
Gastric emptying (GE) of the liquid component was measured in 73 HVs (male 34; aged 45±20). The NTM produced normal postprandial fullness (VAS ≥30 in 41/74 subjects). Dyspeptic symptoms were rare (VAS ≥30 in 2/74 subjects). Gastric emptying half-time with the Liquid- and Solid-component -NTM was median 44 (95% reference interval 28-78) minutes and 162 (144-193) minutes, respectively. Gastric accommodation was assessed by the ratio of the liquid-NTM retained in the proximal:total stomach and by Early phase emptying assessed by gastric volume after completing the meal (GCV0). No consistent effect of anthropometric measures on GE parameters was present.
Reference intervals are presented for GSc measurements of gastric motor and sensory function assessed by the NTM. Studies involving patients are required to determine whether the reference interval range offers optimal diagnostic sensitivity and specificity.
Failure of current investigations to explain the causes of dyspeptic symptoms may be related to small test meals and analysis techniques that rarely detect clinically relevant symptoms. This study provides reference intervals for gastric motor and sensory function by gastric scintigraphy for the large liquid/solid Nottingham test meal (NTM). The NTM is well tolerated and suitable for use in clinical practice.
Significant changes in cervical cancer screening practice, guidelines, and prevention of cervical cancer have taken place in recent years including the raising of initial cervical cancer screening age, changes in frequency of cytology screening, and the adoption of high risk HPV and cytology co-testing for some patients; the introduction of the bivalent, quadrivalent, and 9-valent HPV vaccines; and the recent approval of high risk HPV testing as primary screening with the use of cytology as triage in positive cases. This review discusses the significance of primary HPV screening, the impact of HPV vaccination in the prevalence of cervical cancer and its precursors, the interplay between high risk HPV testing and vaccination, and the implications for clinical and cytological management. Future strategies for cervical screening in the post-vaccination era are also discussed.
Surgical removal plays an important role in treating children’s craniopharyngioma. For a safe and minimally invasive craniotomy, a reformed surgical modality was proposed in this paper by combining the insertion of an Ommaya reservoir system (ORS) by stereotactic puncture, aspiration of cystic fluid in 2-day interval for consecutive 7–10 days, and the delayed tumor resection.
Eleven patients (aged from 5 to 9 years old) with giant cystic craniopharyngiomas who had undergone the reformed surgical modality during November 2014 and December 2015 were collected as group A. In contrast, seven patients (aged from 5 to 11 years old) who had undergone the traditional directed operation without any prior management from January 2014 to October 2014 were collected into group B. A retrospective analysis was performed for both groups at one institution. The preoperative and postoperative clinical presentations, neuroimaging, early postoperative outcome, and the surgery-related complications of both groups were reviewed.
For group A, the mean value of the maximum tumor diameters shank from 52.36 to 23.82 mm after implementing aspiration of the cystic fluid in 1-day interval for consecutive 8.23 days. Eight patients (72.73%) in group A underwent a gross total resection (GTR), while two (28.57%) patients underwent GTR in group B. The postoperative electrolyte disturbance rate and endocrine disorder rate of group B were significantly higher than those of group A (42.86 vs 36.36%; 71.43 vs 45.45%). Postoperative long-term diabetes insipidus only occurred in one patient of group B, and postoperative visual deterioration occurred in two patients of group B. Besides, one patient of group B died of severe postoperative hypothalamus dysfunction. Patients with residual tumors were applied with additional adjuvant radiotherapy, and no recurrence was observed in follow-up examinations.
A favorable outcome can be achieved by combining the insertion of an ORS by stereotactic puncture, aspiration of cystic fluid in 2-day interval for continuously 7–10 days, and the delayed tumor resection. This combined treatment modality maybe an effective method to treat children with giant cystic craniopharyngiomas.
Accurate and timely prenatal diagnosis of spina bifida (SB) is a major goal of modern antenatal care. Prenatal screening for open SB should be first performed at the time of routine first-trimester ultrasound by examining the posterior fossa for obliteration or non-visualization of the fourth ventricle (“intracranial translucency”) and cisterna magna. The second step of screening is the second-trimester anatomy scan, at which time the features of the Chiari type II malformation should be looked for, including ventriculomegaly, scalloping of the frontal bones (“lemon” sign), and backward and caudal displacement of the cerebellar vermis with obliteration of the cisterna magna (“banana” sign). In cases with positive findings, evaluation must include a focused examination of the spine for defects. In cases of closed SB and SB occulta, the cranial and posterior fossa features will not be present as they are not associated with leaking of spinal fluid and resultant hindbrain herniation, highlighting the fact that the spine should be examined thoroughly whenever possible during the second-trimester scan. In tertiary fetal medicine centers, two-dimensional and three-dimensional ultrasound allows an accurate determination of the location, type, extent, and upper level of the spinal defect as well as the presence of associated anomalies. Fetal magnetic resonance imaging should be restricted to candidates for intrauterine surgery as part of the preoperative protocol.
The precise incidence of hydrocephalus in patients with mucopolysaccharidoses (MPS) is hard to determine, because the condition lacks a formal, consensus-based definition. The diagnosis of hydrocephalus depends on symptom profile, presence of neuroimaging features, and the outcome of diagnostic tests. Although numerous techniques are used to identify MPS patients who are most likely to have hydrocephalus and respond to treatment, no definitive method exists to prove diagnosis.
The authors propose an algorithm to aid in the diagnosis and management of hydrocephalus in MPS patients.
The theory of venous hypertension associated with the morphological changes in the skull base and craniocervical junction indicate the need for future neuroimaging studies including cerebrospinal fluid (CSF) and venous flow measurements to monitor hydrocephalus progression and select therapeutic interventions in MPS patients. Preoperative planning should also be based on the increased risk of intraoperative and postoperative hemorrhagic complications.
BCL11A encodes a zinc finger protein that is highly expressed in hematopoietic tissues and the brain, and that is known to function as a transcriptional repressor of fetal hemoglobin (HbF). Recently, de novo variants in BCL11A have been reported in individuals with intellectual disability syndrome without epilepsy. In this study, we performed whole-exome sequencing of 302 patients with epileptic encephalopathies (EEs), and identified two novel BCL11A variants, c.577delC (p.His193Metfs*3) and c.2351A>C (p.Lys784Thr). Both patients shared major physical features characteristic of BCL11A-related intellectual disability syndrome, suggesting that characteristic physical features and the persistence of HbF should lead clinicians to suspect EEs caused by BCL11A pathogenic variants. Patient 1, with a frameshift variant, presented with Lennox–Gastaut syndrome, which expands the phenotypic spectrum of BCL11A haploinsufficiency. Patient 2, with a p.Lys784Thr variant, presented with West syndrome followed by drug-resistant focal seizures and more severe developmental disability. These two newly described patients contribute to delineating the associated, yet uncertain phenotypic characteristics of BCL11A disease-causing variants.
To establish whether existing mutation prediction models can identify which male breast cancer (MBC) patients should be offered BRCA1 and BRCA2 diagnostic DNA screening, we compared the performance of BOADICEA, BRCAPRO and the Myriad prevalence table ('Myriad').
These models were evaluated using the family data of 307 Dutch MBC probands tested for BRCA1/2, 58 (19%) of whom were carriers. We compared the numbers of observed versus predicted carriers and assessed the area under the receiver operating characteristic (ROC) curve (AUC) for each model.
BOADICEA predicted the total number of BRCA1/2 mutation carriers quite accurately (observed/predicted ratio: 0.94). When a cut-off of 10% and 20% prior probability was used, BRCAPRO showed a non-significant better performance (observed/predicted ratio BOADICEA: 0.81, 95% Confidence Interval (CI): (0.60-1.09) and 0.79, 95% CI: (0.57-1.09), vs. BRCAPRO: 1.02, 95% CI: (0.75-1.38) and 0.94, 95% CI: (0.68-1.31), respectively). Myriad underestimated the number of carriers in up to 69% of the cases. BRCAPRO showed a non-significant, higher AUC than BOADICEA (0.798 vs 0.776). Myriad showed a significantly lower AUC (0.671).
BRCAPRO and BOADICEA can efficiently identify MBC patients as BRCA1/2 mutation carriers. Besides their general applicability, these tools will be of particular value in countries with limited healthcare resources.
Advances in clinical genetic testing has led to increased insight into the human genome, including how challenging it is to interpret rare genetic variation. In some cases, the ability to detect genetic mutations exceeds the ability to understand their clinical impact, limiting the advantage of these technologies. Obstacles in genomic medicine are many and include: understanding the level of certainty/uncertainty behind pathogenicity determination, the numerous different variant interpretation-guidelines used by clinical laboratories, delivering the certain or uncertain result to the patient, helping patients evaluate medical decisions in light of uncertainty regarding the consequence of the findings. Through publication of large publicly available exome/genome databases, researchers and physicians are now able to highlight dubious variants previously associated with different cardiac traits. Also, continuous efforts through data sharing, international collaborative efforts to develop disease-gene specific guidelines, and computational analyses using large data, will indubitably assist in better variant interpretation and classification. This paper discusses the current, and quickly changing, state of variant interpretation resources within cardiovascular genetic research, i.e. publicly available databases and ways of how cardiovascular genetic counsellors and geneticists can aid in improving variant interpretation in cardiology.
Distribution of the non-reference allele in SCN5A in Non-Finnish Europeans and African-Americans
Lung cancer is one of the most common cancer types in men and women worldwide with a high mortality rate. World Health Organization (WHO) classification has accepted biopsy as the primary sample for lung cancer diagnosis, pathological classification and molecular testing for management of patients, yet, the use of alternative sampling procedures is highly encouraged. Bronchial cytological samples require a less invasive collection technique and may be suitable for pathological and molecular analysis and storage in liquid medium. Furthermore, the molecular analysis of bronchial cytological samples allows the detection of molecular biomarkers, which may be useful for the selection of molecular targeted therapies. Thus, the purpose of this review is to describe the usefulness of bronchial cytological samples preserved in liquid medium from lung cancer patients for pathological diagnosis and molecular investigation.
Pancreatic neuroendocrine tumors are rare, accounting for less than 3% of all pancreatic tumors. Although laparoscopic pancreas-preserving surgery for managing sporadic pancreatic neuroendocrine tumors has been described in the literature, laparoscopic total pancreatectomy has rarely been reported. We present a 30-year-old man who was incidentally diagnosed with multiple endocrine neoplasia type 1 syndrome with parathyroid hyperplasia and a non-functioning pancreatic neuroendocrine tumor. He underwent laparoscopic total pancreatectomy with splenectomy. This report highlights the technical details of laparoscopic total pancreatectomy, which appears to be a feasible and safe option in select cases.
Prevalence of dental anomalies in cleft patients is higher than that in general population. The objectives of this study were to assess the prevalence of dental anomalies and their coexistence in French children with cleft and, then, to investigate the relation between the dental anomalies and the cleft type.
Seventy-four non-syndromic cleft patients (6–16 years old) from Lille Regional University and Mondor-Chenevier Hospitals (France) were included. Clefts were classified as right/left unilateral cleft lip and palate (UCLP), bilateral cleft lip and palate (BCLP) and cleft palate (CP). Dental anomalies were investigated on panoramic radiographs and categorized as agenesis, supernumerary teeth, incisor rotations, impacted canines and shape anomalies. Prevalence and gender distribution of dental anomalies, mean number of affected teeth per patient, agenesis occurrence and location, and coexistence of dental anomalies were analysed by cleft type.
96.0% of patients presented at least one dental anomaly (agenesis 83.8%, incisor rotations 25.7%, shape anomalies 21.6%, impacted canines 18.9%, supernumerary teeth 8.1%). BCLP patients had a higher number of affected teeth, and left UCLP patients had a higher one compared to right UCLP patients. Distribution of inside (45.3%) and outside (54.7%) cleft region agenesis was similar. Adjacent (31.8%) and not adjacent (33.3%) combined dental anomalies were often encountered.
Dental anomalies were localized inside as well as outside cleft region and were often associated with each other. BCLP patients were more affected.
Early radiographic evaluation allows a comprehensive diagnosis of inside and outside cleft region anomalies, required for the multidisciplinary dental treatment.
The aim of this study was to evaluate and compare the craniofacial cephalometric morphologies among different cleft types in a Spanish population.
A retrospective cross-sectional study was carried out on 212 patients. The patients were subdivided into four groups according to their cleft types: unilateral cleft lip and palate; bilateral cleft lip and palate; cleft lip; and cleft palate. Angular and linear cephalometric measurements were taken on lateral radiographs.
Unilateral cleft lip and palate was associated with a dolichofacial growth pattern, skeletal Class III with correct maxillary position, and lingual incisor inclination. Bilateral cleft lip and palate was associated with a mesofacial growth pattern, skeletal Class I with protruded maxillary position, and lingual incisor inclination. Cleft palate was associated with a mesofacial growth pattern, skeletal Class III with correct maxillary position, and lingual incisor inclination. Cleft lip was associated with a brachyfacial growth pattern, skeletal Class I with protruded maxillary position, lingual upper incisor inclination, and corrects lower incisor inclination. Significant correlations were observed between cleft types and their craniofacial cephalometric measurements.
The present information can be used for the determination of orthodontic treatment and even future orthognathic surgery planning, a requirement in most cleft patients.
This study aimed to (1) analyze the relationships between mandibular symphysis characteristics (height, prominence, inclination, concavity, and convexity) and facial pattern, skeletal class, lower incisor position, and sex, and (2) determine the associations between the symphysis soft tissue dimensions and the underlying osseous structures.
Cone-beam computed tomography (CBCT) images were selected for 385 patients (206 women and 179 men). The patients were classified according to their skeletal class and vertical pattern. The lower incisor inclination (IMPA) was recorded. Twelve measurements were taken for each mandibular symphysis using Invivo5 software (Anatomage, San Jose, CA, USA).
Symphyseal measurements were larger in males than in females. Skeletal Class II and III hyperdivergent patients showed the highest symphysis height values. Hypodivergent individuals showed lower symphysis convexity angles. Concavity of the symphysis was greater for Class II hyperdivergent patients. Lower incisor inclination showed a positive correlation with symphysis concavity and inclination. Moderate and weak correlations were found between hard tissue and soft tissue parameters.
Only a few characteristics of symphysis morphology depend on sex, incisor position, skeletal class, and vertical pattern. More significant relationships are found when the vertical pattern and skeletal class are analyzed in combination. The shape of the symphysis soft tissue is not directly correlated with the underlying skeletal structures.
In Portugal, the industrial production of phosphate fertilizers, has been dealing with a specific raw material—north African phosphate rock—with a high content of trace metals and natural radioactive elements mainly from the 238U decay series. A disabled phosphate plant located in the vicinity of the river Tejo estuary has produced phosphoric acid for several decades (1950–1989) and dumped tons of phosphogypsum (PG) on retention lagoons, formerly decanted and deposited into a stockpile. This paper deals with the assessment of radionuclides, rare earth elements (REEs) and heavy metals transfer to plants (fam. Plantaginaceae, Plantago sp.) and mosses (fam. Bryaceae, Bryum sp.) growing naturally on the PG pile. In Plantago sp., the concentration ratio (CR, plant tissue/PG) was 0.187 for 226Ra and 0.293 for 210Pb. The translocation factor (TF, aerial parts/roots) was 0.781 for 226Ra and 0.361 for 210Pb. In contradiction to the high CR, the leachability of 226Ra from PG was low, lower than 2%. The results confirmed the role of mosses as biomonitors. A high quantity of contaminants collected in its biomass confirmed the hypothesis of their significant transport by air and rain water. High concentrations of heavy metals (As, Cd, Zn, W) in samples collected on the stockpile are an evidence of their transport from former industrial zones in the surroundings and present even more important risk for public health and environment than natural radionuclides and REEs from the PG stockpile.
