Perilesional Reorganization in a Patient With Brain Tumor.

No abstract available

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Burkitt lymphoma as a lead point for jejunojejunal intussusception in a human immunodeficiency virus patient

Abstract

Intussusception is commonly seen in children but is rare in adults and represents only 5% of all intussusceptions causing 1% of intestinal obstructions. More than 50% of these intussusceptions in adults are due to intestinal neoplasms, including malignant lymphoma, e.g., Burkitt lymphoma. These lymphomas are more common in human immunodeficiency virus (HIV)-positive patients than in the general population. We present a case of a young male who was diagnosed with HIV when he developed intestinal obstruction and intussusception secondary to Burkitt lymphoma. He was managed with surgical resection followed by chemotherapy and antiretroviral treatment. HIV patients presenting with acute abdomen pose a diagnostic challenge to clinicians due to a wide range of differential diagnoses including inflammatory, infectious and neoplastic conditions. In a young HIV patient presenting with acute abdomen, intussusception caused by Burkitt lymphoma should be considered in the differential.

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A case of diminished pericardial effusion after treatment of a giant hepatic cyst

Abstract

A 75-year-old woman was discovered to have a pericardial effusion when she was admitted to our hospital because of a giant hepatic cyst. We could not detect the cause of the effusion and diagnosed idiopathic pericardial effusion. The patient underwent transcutaneous drainage of the hepatic cyst and an injection of antibiotics. There was no communication between the pericardial effusion and the hepatic cyst. Although the hepatic cyst was reduced in size, the pericardial effusion showed no remarkable change immediately after treatment; however, 5 months later, the pericardial effusion was found to be diminished. The pericardial effusion might have been caused by the physical pressure of the giant hepatic cyst and disturbance in the balance between the production and reabsorption of the pericardial fluid. When we experience a huge hepatic cyst, we should take into account its influence against the surrounding organs, including the intrapleural space.

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Using Participatory Action Research to Develop a Working Model That Enhances Psychiatric Nurses’ Professionalism: The Architecture of Stability

Abstract

Ward rules in psychiatric care aim to promote safety for both patients and staff. Simultaneously, ward rules are associated with increased patient violence, leading to neither a safe work environment nor a safe caring environment. Although ward rules are routinely used, few studies have explicitly accounted for their impact. To describe the process of a team development project considering ward rule issues, and to develop a working model to empower staff in their daily in-patient psychiatric nursing practices. The design of this study is explorative and descriptive. Participatory action research methodology was applied to understand ward rules. Data consists of audio-recorded group discussions, observations and field notes, together creating a data set of 556 text pages. More than 100 specific ward rules were identified. In this process, the word rules was relinquished in favor of adopting the term principles, since rules are inconsistent with a caring ideology. A linguistic transition led to the development of a framework embracing the (1) Principle of Safety, (2) Principle of Structure and (3) Principle of Interplay. The principles were linked to normative guidelines and applied ethical theories: deontology, consequentialism and ethics of care. The work model reminded staff about the principles, empowered their professional decision-making, decreased collegial conflicts because of increased acceptance for individual decisions, and, in general, improved well-being at work. Furthermore, the work model also empowered staff to find support for their decisions based on principles that are grounded in the ethics of totality.

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Scarlet Fever

http://otorhinolaryngology-crete.blogspot.com/2017/05/scarlet-fever.html

A 20-year-old man presented to his primary care physician with a 3-day history of swollen tonsils, sore throat, fevers, chills, and rash. The nonpruritic rash had started on his abdomen, spread to his chest and back, and then appeared on his arms, legs, and face. He had no known allergies or exposures to new medications and had no history of similar rash. Examination revealed exudative tonsillitis (Panel A), strawberry tongue, and cervical adenopathy with tenderness. Skin examination revealed diffuse blanching erythema with punctate papules that caused the skin on his chest, abdomen, back, arms, and legs to have a sandpaper-like quality (Panel B shows the left side of his abdomen). His neck and right flank had linear petechial patches. A rapid test for streptococcal pharyngitis was positive. The finding of acute streptococcal pharyngitis along with the diffuse rash led to a diagnosis of scarlet fever. The rash of scarlet fever is a delayed-type hypersensitivity to an exotoxin and therefore occurs in persons who have had a previous exposure to Streptococcus pyogenes. The rash classically manifests with linear petechial confluences that are known as Pastia's lines, which were seen in this patient. The patient was treated with antibiotic agents and had complete resolution of his symptoms within 3 days.

Alyson Brinker, M.D.

Navy Hospital Guam, Yigo, Guam 

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182

6948891480

alsfakia@gmail.com

Measurements of rates of cooling of a manikin insulated with different mountain rescue casualty bags

Accidental hypothermia is common in those who sustain injuries in remote environments. This is unpleasant and associated with adverse effects on subsequent patient outcomes. To minimise further heat loss, a ra...

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Molecular Characterization of Multidrug-Resistant Escherichia coli Isolates from Bovine Clinical Mastitis and Pigs in the Vojvodina Province, Serbia

Microbial Drug Resistance , Vol. 0, No. 0.


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Genome-Wide Identification of Potential Drug Target in Enterobacteriaceae Family: A Homology-Based Method

Microbial Drug Resistance , Vol. 0, No. 0.


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Upregulation of AcrEF in Quinolone Resistance Development in Escherichia coli When AcrAB-TolC Function Is Impaired

Microbial Drug Resistance , Vol. 0, No. 0.


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Transoral endoscopic thyroidectomy: our initial experience using a new endoscopic technique

Abstract

Background

A transoral approach has been experimentally introduced to the field of thyroid surgery and several groups in Asia have recently used the technique to treat patients. We performed transoral endoscopic thyroidectomies on patients with thyroid cancer or a benign tumor.

Methods

We reviewed the medical records of patients who underwent transoral endoscopic thyroid surgery between July 2016 and January 2017. A midline incision was made in the vestibule, and a 10 mm cannula was placed; then, the working space was widened by insufflating CO₂ at a pressure of 5–6 mmHg. Two lateral incisions were made in the vestibule near the first molars, and 5-mm-diameter cannulas were inserted. A 10-mm 30° telescope was inserted through the midline cannula and instruments were positioned through the lateral cannulas. Thyroid surgery was endoscopically performed using conventional endoscopic instruments.

Results

We performed 18 thyroid surgeries (15 thyroid lobectomies, one completion thyroidectomy, and two total thyroidectomies) in 17 patients. The postoperative pathology was papillary thyroid cancer in 11 cases (61.1%), a follicular carcinoma in two cases (one patient) (11.1%) and benign in five cases (27.8%). The average tumor diameter was 1.75 cm (range 0.5–7.5 cm). No patient reported sensory changes around the lower lip. No patient developed permanent recurrent laryngeal nerve palsy or hypocalcemia. No patient developed a wound infection or a fistula between the oral incision and anterior neck.

Conclusions

The transoral endoscopic approach provides a short, direct route to the thyroid gland and seems to be safe and feasible. It is important to further develop and refine the surgical techniques. The approach is optimal, and will become widely used for thyroid surgery in the near future.

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Comparison of the multichannel intraluminal impedance pH and conventional pH for measuring esophageal acid exposure: a propensity score-matched analysis

Abstract

Background

The modalities for evaluating acid reflux in medical care for gastroesophageal reflux disease (GERD) include conventional pH (C-pH), wireless pH (Bravo^®) and multichannel intraluminal impedance pH (MII-pH), which have been reported to vary with respect to the duration of acid reflux. In this study, we examined the difference between the acid reflux in C-pH and MII-pH among patients with GERD.

Methods

Prior to initial laparoscopic fundoplication carried out on 297 cases from December 1994 to April 2016, an upper gastrointestinal endoscopy and C-pH or MII-pH were conducted. A propensity score-matched analysis was carried out about five factors including age, sex, BMI, the extent of reflux esophagitis (Los Angeles classification), and the presence of hiatal hernia (HH), ultimately leading to the creation of a C-pH group (81 cases) and MII-pH group (81 cases) as the subjects.

Results

Concerning pH < 4 holding time (18.9 vs. 7.3%, p < 0.001), DeMeester score (58.5 vs. 24.4, p < 0.001), and the number of times reflux continued for longer than 5 min (8.8 vs. 4.1 times/day, p = 0.002), the C-pH group had significantly higher values for each, while the positive rate of acid reflux (Positive pH) was significantly higher in the C-pH group (p < 0.001), at 80% in the C-pH group and 42% in the MII-pH group. In terms of the correlation between the extent of reflux esophagitis and pH < 4 holding time, a moderate level of positive correlation was seen in both the C-pH group and MII-pH group (r of each = 0.427, r = 0.408); moreover, regardless of the presence of HH, the holding time was significantly higher in the C-pH group than the MII-pH group (p of each <0.001, p = 0.040).

Conclusion

While the values of each parameter regarding acid reflux are calculated as lower in MII-pH than in C-pH, there is no difference in the evaluation of the pathology between the two modalities.

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Systematic review and meta-analysis of laparoscopic mesh versus suture repair of hiatus hernia: objective and subjective outcomes

Abstract

Background

Hiatus hernia (HH) contributes to the pathophysiology of gastroesophageal reflux disease (GERD). Mesh-augmentation of surgical repair might be associated with a reduced risk of recurrence and GERD. However, recurrence rates, mesh-associated complications and quality of life (QOL) after mesh versus suture repair are debated. The aim of this meta-analysis was to determine HH recurrence following mesh-augmentation versus suture repair. Secondary aims were to compare complications, mortality, QOL and GERD symptoms following different repair techniques.

Methods

A systematic literature search of the PubMed, Medline, Embase, Cochrane Library, and Springer database was performed to identify relevant studies comparing mesh-augmentation versus suture repair of the esophageal hiatus. Data pertinent to the benefit versus risk outcomes for these techniques were extracted and compared by meta-analysis. The odd ratio (OR) and mean differences (MD) with 95% confidence intervals were calculated.

Results

Eleven studies (4 randomized, 9 non-randomized) comparing mesh (n = 719) versus suture (n = 755) repair were identified. Mesh-augmentation was associated with a reduced overall recurrence rate compared to suture repair [2.6 vs. 9.4%, OR 0.23 (95% CI 0.14–0.39), P < 0.00001]. There was no significant difference in the incidence of complications (P = 0.400) between groups. Improvement in QOL measured by SF-36 was greater following biological mesh-augmentation compared to suture repair (MD = 13.68, 95% CI 2.51–24.85, P = 0.020), as well as GERD-HRQL. No differences were seen for the GIQLI scores with permanent mesh (P = 0.530). Dysphagia improvements were better following suture repair (MD = 1.47, 95% CI 0.20–2.74, P = 0.020).

Conclusions

Mesh repair of HH conferred some advantages and disadvantages at short-term follow-up. Compared to a suture repair alone, mesh-augmentation might be associated with less short-term recurrences, and biological mesh was associated with improved short-term QOL. However, these advantages were offset by more dysphagia. Long-term outcomes are still needed to determine the place of mesh repair of HH.

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Can laparoscopic surgery prevent incisional hernia in patients with Crohn’s disease: a comparison study of 750 patients undergoing open and laparoscopic bowel resection

Abstract

Background

Incisional hernia (IH) is a frequent occurrence following open surgery for Crohn's disease (CD). This study compares the IH rates of patients with CD undergoing open versus laparoscopic bowel resection.

Methods

Seven hundred and fifty patients with CD operated by the authors at the Mount Sinai Medical Center, New York, USA, were reviewed from a prospectively maintained surgical database. Five hundred patients with Crohn's disease undergoing open surgery were compared to 250 patients undergoing laparoscopic bowel resection.

Results

The mean duration of follow-up in the study population was 6.8 years. Patients undergoing open surgery had a significantly higher age at onset of disease, age at surgery, longer duration of disease, lower serum albumin, history of multiple previous resections, were more likely to be on steroids, needed more blood transfusions, and had an increased necessity for an ileostomy during resection. Nevertheless, the incidence of IH at 36 months was nearly identical in both groups (10.8 vs. 8.4% for open vs laparoscopic). 16% of the patients in the laparoscopic group (range: 7–20%) required conversion to open surgery. Patients undergoing laparoscopic resection that required conversion to open surgery had the highest IH rate at 18%. There was a significant correlation between IH and the length of the midline vertical extraction incision. Patients undergoing laparoscopic resection with intracorporeal anastomosis and small transverse or trocar site extraction incisions had no IH.

Conclusions

A marked decrease or complete elimination of IH in patients with CD undergoing bowel resection may be possible using advanced laparoscopic techniques that require intra-abdominal anastomosis and use of the smallest transverse extraction incisions.

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Body Size of Male Youth Soccer Players: 1978–2015

Abstract

Background

Studies of the body size and proportions of athletes have a long history. Comparisons of athletes within specific sports across time, though not extensive, indicate both positive and negative trends.

Objective

To evaluate secular variation in heights and weights of male youth soccer players reported in studies between 1978 and 2015.

Methods

Reported mean ages, heights, and weights of male soccer players 9–18 years of age were extracted from the literature and grouped into two intervals: 1978–99 and 2000–15. A third-order polynomial was fitted to the mean heights and weights across the age range for each interval, while the Preece–Baines model 1 was fitted to the grand means of mean heights and mean weights within each chronological year to estimate ages at peak height velocity and peak weight velocity for each time interval.

Results

Third-order polynomials applied to all data points and estimates based on the Preece–Baines model applied to grand means for each age group provided similar fits. Both indicated secular changes in body size between the two intervals. Secular increases in height and weight between 1978–99 and 2000–15 were especially apparent between 13 and 16 years of age, but estimated ages at peak height velocity (13.01 and 12.91 years) and peak weight velocity (13.86 and 13.77 years) did not differ between the time intervals.

Conclusion

Although the body size of youth soccer players increased between 1978–99 and 2000–15, estimated ages at peak height velocity and peak weight velocity did not change. The increase in height and weight likely reflected improved health and nutritional conditions, in addition to the selectivity of soccer reflected in systematic selection and retention of players advanced in maturity status, and exclusion of late maturing players beginning at about 12–13 years of age. Enhanced training programs aimed at the development of strength and power are probably an additional factor contributing to secular increases in body weight.

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Definition of a RACK1 Interaction Network in Drosophila melanogaster Using SWATH-MS

Receptor for Activated C kinase 1 (RACK1) is a scaffold protein that has been found in association with several signaling complexes, and with the 40S subunit of the ribosome. Using the model organism Drosophila melanogaster, we recently showed that RACK1 is required at the ribosome for IRES-mediated translation of viruses. Here, we report a proteomic characterization of the interactome of RACK1 in Drosophila S2 cells. We carried out Label-Free quantitation using both Data-Dependent and Data-Independent Acquisition and observed a significant advantage for the Sequential Window Acquisition of all THeoretical fragment-ion spectra (SWATH) method both in terms of identification of interactants and quantification of low abundance proteins. These data represent the first SWATH spectral library available for Drosophila and will be a useful resource for the community. A total of 52 interacting proteins were identified, including several molecules involved in translation such as structural components of the ribosome, factors regulating translation initiation or elongation and RNA binding proteins. Among these 52 proteins, 15 were identified as partners by the SWATH strategy only. Interestingly, these 15 proteins are significantly enriched for the functions translation and nucleic acid binding. This enrichment reflects the engagement of RACK1 at the ribosome and highlights the added value of SWATH analysis. A functional screen did not reveal any protein sharing the interesting properties of RACK1, which is required for IRES-dependent translation and not essential for cell viability. Intriguingly however, 10 of the RACK1 partners identified restrict replication of Cricket paralysis virus, an IRES-containing virus.

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Ventricular Action Potential Adaptation to Regular Exercise: Role of {beta}-Adrenergic and KATP Channel Function

Regular exercise-training is known to affect the action potential duration (APD) and improve heart function, but the involvement by β-adrenergic receptor (β-AR) subtypes and/or K_ATP channel is unknown. To address this, female and male Sprague-Dawley rats were randomly assigned to voluntary wheel running or control groups and after 6-8 weeks training anesthetized and myocytes isolated. Exercise-training significantly increased APD of apex and base myocytes at 1Hz, while decreasing the APD at 10Hz. Ca²⁺ transient durations reflected the changes observed in APD, while Ca²⁺ transient amplitudes were unaffected by wheel running. The non-selective β agonist Isoproterenol (ISO) shortened the myocyte APD an effect reduced by wheel running. The ISO-induced shortening of the APD was largely reversed by selective β₁-AR blocker Atenolol, but not the β₂-AR blocker ICI 118,551 providing evidence that wheel running reduced the sensitivity of the β₁-AR. At 10Hz, the KATP channel inhibitor glibenclamide prolonged the myocyte APD more in exercise-trained compared to controls implicating a role for this channel in the exercise-induced APD shortening at 10Hz. A novelty of this work is the demonstration of the duel importance of altered β₁-AR responsiveness and K_ATP channel function in the training-induced regulation of the APD. Of physiological importance to the beating heart, the reduced response to adrenergic agonists would enhance cardiac contractility at resting rates where sympathetic drive is low by prolonging the APD and Ca²⁺ influx, while during exercise an increased K_ATP channel activity would shorten APD thus protecting the heart against Ca²⁺ overload or inadequate filling.

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Individual hemoglobin mass response to normobaric and hypobaric "live high-train low": A one-year crossover study

Purpose: To compare individual hemoglobin mass (Hb_mass) changes following a live high-train low (LHTL) altitude training camp under either normobaric hypoxia (NH) or hypobaric hypoxia (HH) conditions in endurance athletes. Methods: In a crossover design with a one-year washout, 15 male triathletes randomly performed two 18-d LHTL training camps in either HH or NH. All athletes slept at 2250 m and trained at altitudes < 1200 m. Hb_mass was measured in duplicate with the optimized carbon monoxide rebreathing method before (pre-) and immediately after (post-) each 18 d training camp. Results: Hb_mass increased similarly in HH (916 to 957 g, 4.5 ± 2.2%, P < 0.001) and in NH (918 to 953 g, 3.8 ± 2.6%, P < 0.001). Hb_mass changes did not differ between HH and NH (P = 0.42). There was substantial inter-individual variability among subjects to both interventions (i.e., individual responsiveness, or the individual variation in the response to an intervention free of technical noise): 0.9% in HH and 1.7% in NH. However, a correlation between intra-individual delta Hb_mass changes (%) in HH and in NH (r = 0.52, P = 0.048) was observed. Conclusion: HH and NH evoked similar mean Hb_mass increases following LHTL. Among the mean Hb_mass changes, there was a notable variation in individual Hb_mass response, which tended to be reproducible.

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Aortic arch compliance and idiopathic unilateral vocal fold paralysis

Unilateral vocal fold paralysis (UVP) occurs related to recurrent laryngeal nerve (RLN) impairment associated with impaired swallowing, voice production, and breathing functions. The majority of UVP cases occur subsequent to surgical intervention with approximately 12-42% having no known cause for the disease (i.e., idiopathic). Approximately 2/3 of those with UVP exhibit left-sided injury with the average onset at 50 years of age or older in those diagnosed as idiopathic. Given the association between the RLN and the subclavian and aortic arch vessels, we hypothesized that changes in vascular tissues would result in increased aortic compliance in idiopathic left-sided UVP patients compared to those without UVP. Gated MRI data enabled aortic arch diameter measures normalized to blood pressure across the cardiac cycles to derive aortic arch compliance. Compliance was compared between individuals with left-sided idiopathic UVP and age- and gender-matched normal controls. Three-way factorial ANOVA test showed that aortic arch compliance (p=0.02) and aortic arch diameter change in one cardiac cycle (p=0.04) are significantly higher in idiopathic left-sided UVP patients compared to the controls. As previously demonstrated by other literature, our finding confirmed that compliance decreases with age (p<0.0001) in both healthy and idiopathic UVP patients. Future studies will investigate parameters of aortic compliance change as a potential contributor to the onset of left-sided UVP.

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Ontogeny of myosin isoform expression and prehensile function in the tail of the gray short-tailed opossum (Monodelphis domestica)

Terrestrial opossums use their semi-prehensile tail for grasping nesting materials as opposed to arboreal maneuvering. We relate the development of this adaptive behavior with ontogenetic changes in myosin heavy chain (MHC) isoform expression from 21 days to adulthood. Monodelphis domestica is expected to demonstrate a progressive ability to flex the distal tail up to age 7 months, when it should exhibit routine nest construction. We hypothesize that juvenile stages (3-7 months) will be characterized by retention of the neonatal isoform (MHC-Neo), along with predominant expression of fast MHC-2X and 2B, which will transition into greater MHC-1β and 2A isoform content as development progresses. This hypothesis was tested using Q-PCR to quantify and compare gene expression of each isoform to its protein content determined by gel electrophoresis and densitometry. These data were correlated with nesting activity in an age-matched sample of each age group studied. Shifts in regulation of MHC gene transcripts matched well with isoform expression. Notably, mRNA for MHC-Neo and 2B decrease, resulting in little-to-no isoform translation after age 7 months, whereas mRNA for MHC-1β and 2A increase, and this corresponds with subtle increases in content for these isoforms into late adulthood. Despite the tail remaining intrinsically fast-contracting, a critical growth period for isoform transition is observed between 7 and 13 months, correlating primarily with use of the tail during nesting activities. Functional transitions in MHC isoforms and fiber type properties may be associated with muscle 'tuning' repetitive nest remodeling tasks requiring sustained contractions of the caudal flexors.

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Effect of Cyclooxygenase Inhibition on the Inspiratory Muscle Metaboreflex-Induced Cardiovascular Consequences in Men

Inspiratory muscle metaboreflex activation increases mean arterial pressure (MAP) and limb vascular resistance (LVR) and decreases limb blood flow (Q_L). Cyclooxygenase (COX) inhibition has been found to attenuate limb skeletal muscle metaboreflex-induced increases in muscle sympathetic nerve activity. We hypothesized that compared to placebo (PLA), COX inhibition would attenuate inspiratory muscle metaboreflex-induced 1) increases in MAP and LVR and 2) decreases in Q_L. Seven men (22±1 years) were recruited and orally consumed ibuprofen (IB, 10mg/kg) or PLA 90 min prior to performing the cold pressor test (CPT) for 2 min and inspiratory resistive breathing task (IRBT) for 14.9±2.0min at 65% of maximal inspiratory pressure. Breathing frequency was 20 breaths per min with a 50% duty cycle during the IRBTs. MAP was measured via automated oscillometry, Q_L was determined via Doppler ultrasound, and LVR was calculated as MAP divided by Q_L. EMG was recorded on the leg to ensure no muscle contraction occurred. The 65% IRBT led to greater increases (p=0.02) in 6-keto-PGF_1α with PLA compared to IB. IB, compared to PLA, led to greater (p<0.01) increases in MAP (IB: 17±7mmHg vs. PLA: 8±5mmHg) and LVR (IB: 69±28% vs. PLA: 52±22%) at the final min of the 65% IRBT. The decrease in Q_L was not different (p=0.72) between IB (-28±11%) and PLA (-27±9%) at the final min. The increase in MAP during the CPT was not different (p=0.87) between IB (25±11mmHg) and PLA (24±6mmHg). Contrary to our hypotheses, COX inhibition led to greater inspiratory muscle metaboreflex-induced increases in MAP and LVR.

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Exercise training in Tg{alpha}q*44 mice during the progression of chronic heart failure: cardiac vs. peripheral (soleus muscle) impairments to oxidative metabolism

Cardiac function, skeletal (soleus) muscle oxidative metabolism and the effects of exercise training were evaluated in a transgenic murine model (Tgα_q*44) of chronic heart failure (CHF) during the critical period between the occurrence of an impairment of cardiac function and the stage at which overt cardiac failure ensues (i.e. from 10 to 12 months of age). Forty-eight Tgα_q*44 mice and 43 wild-type (WT) FVB controls were randomly assigned to control groups and to groups undergoing 2 months of intense exercise training (spontaneous running on a instrumented wheel). In mice evaluated at the beginning and at the end of training we determined: exercise performance (mean distance covered daily on the wheel); cardiac function in vivo (by magnetic resonance imaging); soleus mitochondrial respiration ex vivo (by high-resolution respirometry); muscle phenotype (myosin heavy chain [MHC] isoforms content; citrate synthase [CS] activity) and variables related to the energy status of muscle fibers (p-AMPK/AMPK) and mitochondrial biogenesis and function (PGC-1α). In the untrained Tgα_q*44 mice functional impairments of exercise performance, cardiac function and soleus muscle mitochondrial respiration were observed. The impairment of mitochondrial respiration was related to the function of complex I of the respiratory chain, and it was not associated with differences in CS activity, MHC isoforms, p-AMPK/AMPK and PGC-1α levels. Exercise training improved exercise performance and cardiac function, but it did not affect mitochondrial respiration, even in the presence of an increased % of type 1 MHC isoforms. Factors "upstream" of mitochondria were likely mainly responsible for the improved exercise performance.

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Postmeal exercise blunts postprandial glucose excursions in people on metformin monotherapy.

Metformin is used clinically to reduce fasting glucose with minimal effects on postprandial glucose. Postmeal exercise reduces postprandial glucose and may offer additional glucose-lowering benefit beyond that of metformin alone, yet controversy exists surrounding exercise and metformin interactions. It is currently unknown how postmeal exercise and metformin monotherapy in combination will affect postprandial glucose. Thus, we examined the independent and combined effects of postmeal exercise and metformin monotherapy on postprandial glucose. A randomized-crossover design was used to assess the influence of postmeal exercise on postprandial glucose excursions in 10 people treated with metformin monotherapy (57 ± 10 yrs, HbA_1C = 6.3 ± 0.6%). Each participant completed four conditions: sedentary and postmeal exercise (5 x 10-min bouts of treadmill walking at 60% VO₂ max) with metformin, and sedentary and postmeal exercise without metformin. Peak postprandial glucose within a 2-hr time window and 2-hr total area-under the-curve were assessed after a standardized breakfast meal, using continuous glucose monitoring. Postmeal exercise significantly blunted 2-hr peak (p = 0.001) and 2-hr AUC (p = 0.006), with the lowest peak postprandial glucose excursion observed with postmeal exercise and metformin combined (p < 0.05 vs. all other conditions: met/sed: 12 ± 3.4, met/ex: 9.7 ± 2.3, washout/sed: 13.3 ± 3.2, washout/ex: 11.1 ± 3.4 mmol/L). Postmeal exercise and metformin in combination resulted in the lowest peak postprandial glucose excursion compared to either treatment modality alone. Exercise timed to the postprandial phase may be important for optimizing glucose control during metformin monotherapy.

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Obesity-induced discrepancy between contractile and metabolic phenotypes in slow- and fast-twitch skeletal muscles of female obese Zucker rats

A clear picture of skeletal muscle adaptations to obesity and related comorbidities remains elusive. This study describes fiber-type characteristics (size, proportions, and oxidative enzyme activity) in two typical hind limb muscles with opposite structure and function in an animal model of genetic obesity. Lesser fiber diameter, fiber type composition, and histochemical succinic dehydrogenase activity (an oxidative marker) of muscle fiber types were assessed in slow- (soleus) and fast-twitch (tibialis cranialis) muscles of obese Zucker rats, and compared with age- (16 weeks) and sex-matched (females) lean Zucker rats (N=16/group). Muscle mass and lesser fiber diameter were lower in both muscle types of obese compared with lean animals, even though body weights were increased in the obese cohort. A faster fiber-type phenotype also occurred in slow- and fast-twitch muscles of obese rats, compared with lean rats. These adaptations were accompanied by a significant increment in histochemical succinic dehydrogenase activity of slow-twitch fibers in the soleus muscle, and fast-twitch fiber-types in the tibialis cranialis muscle. Obesity significantly increased plasma levels of pro-inflammatory cytokines, but did not significantly affect protein levels of peroxisome proliferator activated receptors PPAR and PGC1α in both muscles. These data demonstrate that, in female Zucker rats, obesity induces a reduction of muscle mass in which skeletal muscles show a diminished fiber size and a faster and more oxidative phenotype. It was noteworthy that this discrepancy in muscle's contractile and metabolic features was of comparable nature and extent in muscles with different fiber-type composition and antagonist functions.

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On the existence of a central respiratory oxygen sensor

A commonly held view that dominates both the scientific and educational literature is that in terrestrial mammals the central nervous system lacks a physiological hypoxia sensor capable of triggering increases in lung ventilation in response to decreases in PO₂ of the brain parenchyma. Indeed, a normocapnic hypoxic ventilatory response has never been observed in humans following bilateral resection of the carotid bodies. In contrast, almost complete or partial recovery of the hypoxic ventilatory response after denervation/removal of the peripheral respiratory oxygen chemoreceptors has been demonstrated in many experimental animals when assessed in an awake state. In this essay we review the experimental evidence obtained using in vitro and in vivo animal models, results of human studies, and discuss potential mechanisms underlying the effects of CNS hypoxia on breathing. We consider experimental limitations and discuss potential reasons why the recovery of the hypoxic ventilatory response has not been observed in humans. We review recent experimental evidence suggesting that the lower brainstem contains functional respiratory oxygen sensitive elements capable of stimulating respiratory activity independently of peripheral chemoreceptor input.

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Regulation of Erythropoiesis after Normoxic Return from Chronic Sustained and Intermittent Hypoxia.

Hypoxia increases erythropoiesis mediated by hypoxia-inducible transcription factors (HIF) which regulate erythropoietin (EPO) transcription. Neocytolysis is a physiological mechanism that corrects polycythemia from chronic sustained hypoxemia (CSH) by transient, preferential destruction of young RBCs after normoxia is restored. We showed that neocytolysis is caused by excessive mitochondrial-derived reactive oxygen species (ROS) in reticulocytes mediated by down-regulation of HIF-controlled BNIP3L regulated mitophagy and a decrease in RBC antioxidant catalase (CAT) in hypoxia-produced erythrocytes. Decreased CAT results from hypoxia-induced miR-21 that downregulates CAT. This correlates with a transient acute decrease of HIF-1 at normoxic return that is associated with normalization of red cell mass. Obstructive sleep apnea (OSA), characterized by a unique pattern of chronic intermittent hypoxia (CIH), is associated with cardiovascular, endocrine and neurocognitive comorbidities, and increased cancer risk. The role of the carotid body in OSA modulated pathophysiologies has been well-studied; here we define hematological abnormalities and discuss the possible role of OSA blood changes on health. We found that only ~1% of OSA patients developed polycythemia, which was not attributable to other causes and corrected with continuous positive airway pressure therapy (CPAP) therapy. However, in our pilot OSA studies, we found increased ROS and mitochondrial mass with decreased CAT and BNIP3L in blood cells, along with increased inflammatory markers. After correction of OSA with use of CPAP for >3 months, some, but not all of these abnormalities corrected. The observed blood changes in OSA likely contribute to impaired health; however, their pathophysiological roles need to be carefully defined.

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Increased Left Ventricular Extracellular Volume and Enhanced Twist Function in Type 1 Diabetic Individuals

Individuals with type 1 diabetes (T1D) characteristically have high glycemic levels that over time can result in reactive fibrosis and abnormalities in myocardial function. T₁ mapping with magnetic resonance imaging (MRI) can estimate the extent of reactive fibrosis by measurement of the extracellular volume fraction (ECV). The extent of alterations in the ECV and associated changes in left ventricular (LV) function and morphology in individuals with T1D is unknown. Fourteen individuals with long-term T1D and fourteen sex-, age-, and body mass index-matched controls without diabetes underwent MRI measurement of myocardial T₁ and ECV values as well as LV function and morphology. Ventricular mass, volumes and global function (LVEF, circumferential/longitudinal/radial strain) were similar in those with T1D and controls. However, those with T1D had larger myocardial ECV (0.221±0.018 versus 0.201±0.021, P=0.008) and increased native (non-contrast) myocardial T₁ values (1211±44ms versus 1172±43ms, P<0.001) as compared to controls. Both the ECV and native T₁ values significantly correlated with several components of torsion and circumferential-longitudinal shear strain (E_cl, the shear strain component associated with twist). Individuals with T1D had increased systolic torsion (P=0.035), systolic torsion rate (P=0.032), peak E_cl (P=0.001) and rates of change of systolic (P=0.007) and diastolic (P=0.007) E_cl. Individuals with T1D, with normal structure, LVEF and strain, have increased extracellular volume and increased native T₁ values with associated augmented torsion and E_cl. These measures may be useful in detecting the early stages of diabetic cardiomyopathy and warrant larger prospective studies.

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Functional assessment of the diaphragm by speckle tracking ultrasound during inspiratory loading

Background: Assessment of diaphragmatic effort is challenging especially in critically ill patients in the phase of weaning. Fractional thickening during inspiration assessed by ultrasound has been used to estimate diaphragm effort. It is unknown whether more sophisticated ultrasound techniques such as speckle tracking are superior in the quantification of inspiratory effort. This study evaluates the validity of speckle tracking ultrasound to quantify diaphragm contractility. Methods: Thirteen healthy volunteers underwent a randomized stepwise threshold loading protocol of 0 to 50% of the maximal inspiratory pressure. Electric activity of the diaphragm and transdiaphragmatic pressures were recorded. Speckle tracking ultrasound was used to assess strain and strain rate as measures of diaphragm tissue deformation and deformation velocity, respectively. Fractional thickening was assessed by measurement of diaphragm thickness at end-inspiration and end-expiration. Results: Strain and strain rate increased with progressive loading of the diaphragm. Both strain and strain rate were highly correlated to transdiaphragmatic pressure (strain R²=0.72; strain rate R²=0.80) and diaphragm electric activity (strain R²=0.60; strain rate R²=0.66). No correlation between fractional thickening and strain and strain rate was found. Conclusion: Speckle tracking ultrasound is superior to conventional ultrasound techniques to estimate diaphragm contractility under inspiratory threshold loading.

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A model for in vivo analysis of sudomotor sympathetic C-fiber activation and human sweat gland output

Quantitative assessment of small fiber peripheral neuropathy often involves an evaluation of the interaction between the C-fiber sudomotor nerve and local sweat rate (SR). Typically, some sort of quantitative sudomotor axon reflex test (QSART) is performed to aid in diagnosing small fiber dysfunction. The currently used QSART demonstrates only moderate test-retest reliability and therefore limits its usefulness in tracking small fiber dysfunction. A new experimental model to examine small C-fiber function in the skin using intradermal electrical stimulation and simultaneous monitoring of SR is proposed. Using intradermal electrical stimulation (1.5 and 2.5 mA) and varying stimulus frequency from 0.2 - 64 Hz a quantitative relationship between the area under the SR - time curve and log₁₀ stimulus frequency is modeled using a four-parameter logistic equation, providing the following parameters: Baseline, Plateau, EC₅₀, and Hill slope. The model has good to excellent repeatability within the same day (ICC = 0.98), on different days at the same skin site (ICC = 0.80), and when comparing two different skin sites (ICC = 0.78) with a small bias estimate and the line of identity always lying within the 95% limits of agreement. Atropine sulfate (0.1 mg•ml^-1) blocked 90 ± 5% of the electrically induced sweating. Overall, the model provides control over sudomotor nerve activity and a quantitative assessment of SR. Finally, the ability to reproduce quantitative stimulus-response curve on different days allows for a robust assessment of the relationship between the activation of a sympathetic C-fiber and local SR.

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Influence of sex, menstrual cycle and oral contraceptives on cerebrovascular resistance and cardiorespiratory function during Valsalva or standing

Women experience orthostatic intolerance more than men, and experience faintness more in the early follicular (i.e. low hormone (LH)) compared to the luteal (i.e. high hormone (HH)) phase of the menstrual cycle. Men (n=13, age: 25.8±1.8) and women in the LH (day 2-5; placebo) and HH) (day 18-24; high dose) phases of the menstrual cycle with (OC; n=14, age: 22.0±0.8) or without oral contraceptives (NOC; n=12, age: 21.8±0.5) underwent the Valsalva maneuver and a supine-sit-stand protocol. Blood pressure, normalized stroke volume (SVi), cardiac output index (Qi), heart rate (HR), end-tidal carbon dioxide (ET-CO₂), and middle cerebral artery blood velocity (MCA) were measured. Valsalva: All women had a greater increase in diastolic and mean MCA compared to men (p≤0.065) with no significant effect of menstrual cycle or OC use. Supine-sit-stand: Sex: Men had lower MCA (p<0.038) than all women, and higher SVi compared to NOC in all postures (p<0.011) and OC-LH during stand (p=0.010). Only men experienced higher resistance index (RI; p<0.001) and pulsatility index (PI; p<0.001) with standing. OC: OC had lower ET-CO₂ (p=0.002) compared to NOC (p=0.030) and men (p≤0.067). Compared to NOC, OC had higher SVi (p=0.004) and Qi (p=0.008). Phase: HH tended to have lower mean MCA (p=0.058) and higher SVi (p=0.059) and PI (p=0.058) than LH. OC x Phase: OC users had higher MAP than NOC in LH (p=0.049) and lower MAP in HH compared to themselves in LH (p=0.014). Our results indicate that cycling estrogens/progestins can influence ventilatory, cardiovascular and/or cerebrovascular physiology.

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Physical interface dynamics alter how robotic exosuits augment human movement: implications for optimizing wearable assistive devices

Wearable assistive devices have demonstrated the potential to improve mobility outcomes for individuals with disabilities, and to augment healthy human performance; however, these benefits depend on how effect...

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Bioinformaticians wrestling with the big biomedical data

Publication date: Available online 18 May 2017
Source:Journal of Genetics and Genomics
Author(s): Yu Xue, Xiu-Jie Wang




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Attenuated Error-Related Potentials in Amyotrophic Lateral Sclerosis with Executive Dysfunctions

Amyotrophic lateral sclerosis (ALS) is the most common form of motor neuron diseases. It is characterized by progressive degeneration of the upper and lower motor neuron, resulting in muscle paralysis and atrophy. Despite intensive research, curative therapy is still not available. The prognosis is fatal, with a median survival of 2-5 years after disease onset. The incidence in Europe is 2.16 per 100,000 (Logroscino et al., 2010). Different genetic mutations have been associated with the familial form of disease (Robberecht and Philips, 2013), but the etiology of the more common sporadic ALS (90% of cases) remains largely unknown.

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Phase-locked and non-phase-locked EEG responses to pinprick stimulation before and after experimentally-induced secondary hyperalgesia

Intense or sustained nociceptor activation, induced for example by capsaicin or high frequency electrical stimulation (HFS), triggers an activity-dependent long-lasting, but reversible, long-term potentiation (LTP) in spinal nociceptive pathways (Sandkühler, 2007). In humans, topical capsaicin or HFS of the skin induces hyperalgesia in the treated area ("primary" hyperalgesia, LaMotte et al., 1991; Klein et al., 2004; Henrich et al., 2015). This primary hyperalgesia is thought to result from both a peripheral sensitization of nociceptors and LTP in spinal nociceptive pathways (Sandkühler and Gruber-Schoffnegger, 2012).

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Influence of transcutaneous spinal stimulation on human LTP-like pain amplification. A randomized, double-blind study in volunteers

Non-invasive transcutaneous spinal direct current stimulation (tsDCS) has been proven to affect nociceptive circuits in healthy individuals and might be promising in pain treatment (Priori et al. 2014).

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Patient and physician views on the quality of care for inflammatory bowel disease after one-year follow-up: Results from SOLUTION-2, a prospective IG-IBD study

Perception of quality of care is important in the management of patients with chronic diseases, particularly inflammatory bowel disease.

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Cytology Brushing of a Pancreas Cyst Wall for the Diagnosis of Cystic Neuroendocrine Tumor: When FNA Fails

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Duodenal Gangliocytic Paraganglioma: Endoscopy, Sonography and F-18 FDG PET/CT imaging

We report a case of duodenal gangliocytic paraganglioma (GP). Duodenal GP is a rare subepithelial lesion that typically arises from the region of the major duodenal papilla. It is the third most common duodenal neuroendocrine tumor (NET), after gastrinoma and somatostatinoma. According to the World Health Organization classification, duodenal GP is considered a benign lesion, even though occasionally it may exhibit regional lymph node metastasis. Its clinical manifestations include gastrointestinal bleeding, abdominal pain and anemia.

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ISYQOL: a rasch-consistent questionnaire for measuring health-related quality of life in adolescents with spinal deformities

– Spinal deformities are commonly associated with poor HRQOL. Several questionnaires (e.g. SRS-24 and SRS-22) have been developed to evaluate HRQOL in these conditions. In adults as well as during growth, the HRQOL is considered one of the most relevant outcomes of both conservative and surgical treatment. Rasch analysis is a powerful statistical technique for developing high quality and valid questionnaires. The SRS-24 and SRS-22 have been evaluated using the Rasch analysis, but showed poor measurement properties.

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Patient and physician views on the quality of care for inflammatory bowel disease after one-year follow-up: Results from SOLUTION-2, a prospective IG-IBD study

Perception of quality of care is important in the management of patients with chronic diseases, particularly inflammatory bowel disease.

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Cytology Brushing of a Pancreas Cyst Wall for the Diagnosis of Cystic Neuroendocrine Tumor: When FNA Fails

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Duodenal Gangliocytic Paraganglioma: Endoscopy, Sonography and F-18 FDG PET/CT imaging

We report a case of duodenal gangliocytic paraganglioma (GP). Duodenal GP is a rare subepithelial lesion that typically arises from the region of the major duodenal papilla. It is the third most common duodenal neuroendocrine tumor (NET), after gastrinoma and somatostatinoma. According to the World Health Organization classification, duodenal GP is considered a benign lesion, even though occasionally it may exhibit regional lymph node metastasis. Its clinical manifestations include gastrointestinal bleeding, abdominal pain and anemia.

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Two mitogenomes in Gruiformes ( Amaurornis akool / A. phoenicurus ) and the phylogenetic placement of Rallidae

Abstract

Rallidae, with 34 genera including 142 species, is the largest family in the Gruiformes, the phylogenetic placement of this family was still in debate. The complete mitochondrial genomes (mitogenomes), with many advantageous characters, have become popular markers in phylogenetic analyses. We sequenced the mitogenomes of brown crake (Amaurornis akool) and white-breasted waterhen (Amaurornis phoenicurus), analyzed the genomic characters of mitogenomes in Rallidae, and explored the phylogenetic relationships between Rallidae and other four families in Gruiformes based on mitogenome sequences of 32 species with Bayesian method. The mitogenome of A. akool/A. phoenicurus was 16,950/17,213 bp in length, and contained 37 genes typical to avian mitogenomes and one control region, respectively. The genomic characters of mitogenomes in Rallidae were similar. The phylogenetic results indicated that, among five families, Rallidae had closest relationship with Heliornithidae, which formed a sister taxa to Gruidae, while Rhynochetidae located in the basal lineage. Within Rallidae, Rallina was ancestral clade. Gallirallus & Rallus and Aramides were closely related, Gallicrex & Amaurornis and Fulica & Gallinula had close relationships, and these two taxa formed a sister clade to Porphyrio & Coturnicops. Our phylogenetic analyses provided solid evidence for the phylogenetic placement of Rallidae and the evolutionary relationships among different genus within this family. In addition, the mitogenome data presented here provide useful information for further molecular systematic investigations on Gruiformes as well as conservation biology research of these species.

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EMS Week 2017: What it means to be 'Always in Service'

"Always in Service" is the 2017 EMS Week theme. Like the themes from previous years – "Called to Care" and "Everyday Heroes" – this year's theme of "Always in Service" is not explicitly defined and it is under the umbrella of EMS Strong. EMS Week is an annual celebration and recognition of EMS providers. The American College of Emergency Physicians ...

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Evaluating the potential for tactical hunting in the Middle Stone Age: Insights from a bonebed of the extinct bovid, Rusingoryx atopocranion

Publication date: July 2017
Source:Journal of Human Evolution, Volume 108
Author(s): Kirsten E. Jenkins, Sheila Nightingale, J. Tyler Faith, Daniel J. Peppe, Lauren A. Michel, Steven G. Driese, Kieran P. McNulty, Christian A. Tryon
The foraging behaviors of Middle Stone Age (MSA) early modern humans have largely been based on evidence from well-stratified cave sites in South Africa. Whereas these sites have provided an abundance of data for behavioral reconstruction that are unmatched elsewhere in Africa, they are unlikely to preserve evidence of the diversity of foraging strategies employed by MSA hunters who lived in a variety of ecological and landscape settings across the African continent. Here we describe the results of recent excavations at the open-air site of Bovid Hill at Wakondo, Rusinga Island, Kenya, which yielded 24 in situ MSA artifacts within an assemblage of bones comprised exclusively of the extinct alcelaphin bovid Rusingoryx atopocranion. The excavated faunal assemblage is characterized by a prime-age-dominated mortality profile and includes cut-marked specimens and an associated MSA Levallois blade-based artifact industry recovered from a channel deposit dated to 68 ± 5 ka by optically stimulated luminescence. Taphonomic, geologic, and faunal evidence points to mass exploitation of Rusingoryx by humans at Bovid Hill, which likely represents an initial processing site that was altered post-depositionally by fluvial processes. This site highlights the importance of rivers and streams for mass procurement in an open and seasonal landscape, and provides important new insights into MSA behavioral variability with respect to environmental conditions, site function, and tactical foraging strategies in eastern Africa. Bovid Hill thus joins a growing number of MSA and Middle Paleolithic localities that are suggestive of tactical hunting behaviors and mass capture of gregarious ungulate prey.



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Selection to outsmart the germs: The evolution of disease recognition and social cognition

Publication date: July 2017
Source:Journal of Human Evolution, Volume 108
Author(s): Sharon E. Kessler, Tyler R. Bonnell, Richard W. Byrne, Colin A. Chapman
The emergence of providing care to diseased conspecifics must have been a turning point during the evolution of hominin sociality. On a population level, care may have minimized the costs of socially transmitted diseases at a time of increasing social complexity, although individual care-givers probably incurred increased transmission risks. We propose that care-giving likely originated within kin networks, where the costs may have been balanced by fitness increases obtained through caring for ill kin. We test a novel hypothesis of hominin cognitive evolution in which disease may have selected for the cognitive ability to recognize when a conspecific is infected. Because diseases may produce symptoms that are likely detectable via the perceptual-cognitive pathways integral to social cognition, we suggest that disease recognition and social cognition may have evolved together. Using agent-based modeling, we test 1) under what conditions disease can select for increasing disease recognition and care-giving among kin, 2) whether providing care produces greater selection for cognition than an avoidance strategy, and 3) whether care-giving alters the progression of the disease through the population. The greatest selection was produced by diseases with lower risks to the care-giver and prevalences low enough not to disrupt the kin networks. When care-giving and avoidance strategies were compared, only care-giving reduced the severity of the disease outbreaks and subsequent population crashes. The greatest selection for increased cognitive abilities occurred early in the model runs when the outbreaks and population crashes were most severe. Therefore, over the course of human evolution, repeated introductions of novel diseases into naïve populations could have produced sustained selection for increased disease recognition and care-giving behavior, leading to the evolution of increased cognition, social complexity, and, eventually, medical care in humans. Finally, we lay out predictions derived from our disease recognition hypothesis that we encourage paleoanthropologists, bioarchaeologists, primatologists, and paleogeneticists to test.



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Subsistence strategies during the Late Pleistocene in the southern Cape of South Africa: Comparing the Still Bay of Blombos Cave with the Howiesons Poort of Klipdrift Shelter

Publication date: July 2017
Source:Journal of Human Evolution, Volume 108
Author(s): Jerome P. Reynard, Christopher S. Henshilwood
The Still Bay (SB) and Howiesons Poort (HP) were two significant techno-complexes in the Middle Stone Age and key periods in the expression of behavioral complexity. In this study, we compare the recently excavated fauna from the SB layers at Blombos Cave (BBC) with that from the HP levels at Klipdrift Shelter (KDS) in the southern Cape of South Africa. We consider our findings in the framework of recent models for early human subsistence behavior. In particular, we link our study with models involving resource intensification to examine whether foraging strategies in the HP were more or less intensive than those in the SB. Based on our criteria used to assess intensification—the exploitation of low-ranked prey, the processing of low-utility elements, transport decisions, and occupational intensity—intensive subsistence strategies are more evident at KDS than BBC. Our results suggest that low-ranked elements were processed more heavily and diet breath was broader at KDS than at BBC. However, foraging ranges may have been more extensive at BBC than at KDS. Taphonomic data also suggests that the SB at BBC was a low-intensity, sporadically occupied period in contrast to the high-intensity occupations during the HP at KDS. We argue that this may be related to differences in mobility and residential patterns between these techno-complexes.



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Editors’ Introduction to the Chronic Pancreatitis and Pancreatic Cysts Special Issue

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Medical Management of Pain in Chronic Pancreatitis

Abstract

The medical management of pain in chronic pancreatitis continues to pose significant challenges for clinicians caring for these patients. There are increasing data, suggesting that pain in chronic pancreatitis is largely due to peripheral and central sensitization that evolves, over time, as a result of nociceptive afferent associated with chronic inflammation and fibrosis of the pancreas. In many instances, patients rapidly progress to requiring opioid analgesics for the adequate treatment of pain despite the unequivocal risks associated with the long-term use of these drugs. Centrally acting drugs, such as gabapentinoids, appear to be effective means of treating pain due to their inhibition of neurotransmitters involved in central sensitization, but side effects limit their use. The present review explores the evidence for various non-pharmacologic and pharmacologic treatments for pain in chronic pancreatitis.

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Activation of NLRP3 Inflammasome in Inflammatory Bowel Disease: Differences Between Crohn’s Disease and Ulcerative Colitis

Abstract

Background

NLRP3 inflammasome is a multimolecular cytosol complex that, when activated, contributes to the cleavage of pro-interleukin (IL)-1β to IL-1β.

Aims

To investigate NLRP3 inflammasome activation in inflammatory bowel disease.

Methods

Peripheral blood mononuclear cells from Crohn's disease (CD), ulcerative colitis (UC) patients and controls were stimulated with LPS in the absence or presence of MSU. After incubation, concentrations of IL-1β, IL-6, and TNFα were measured in cell supernatants and concentration of pro-IL-1β was measured in cell lysates. NLRP3 activation was defined as more than 30% increase in IL-1β production after MSU addition. In separate experiments, PBMCs were lysed for RNA isolation transcripts of IL-1β, TNFα, NLRP3, and CASP1 were measured by RT-PCR. DNA was isolated from CD patients for ATG16L1 gene genotyping.

Results

NLRP3 inflammasome was activated in 60% of CD patients compared to 28.6% of controls (p = 0.042); no significant difference was detected between UC and controls. Among UC patients, NLRP3 activation was associated (p = 0.008) with long-standing disease (>1.5 years). IL-1β levels were significantly higher in CD patents in comparison with controls (p = 0.032). No difference was detected in the levels of IL-6, TNFα, pro-IL-1β and in the numbers IL-1β, TNFα, NLRP3, and CASP1 transcripts among groups. IL-1β production was similar between carriers of wild-type and of SNP alleles of the rs2241880.

Conclusions

NLRP3 inflammasome is activated in CD patients and in UC patients with long-standing disease.

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ZNF281 Promotes Growth and Invasion of Pancreatic Cancer Cells by Activating Wnt/β-Catenin Signaling

Abstract

Background

Zinc finger protein 281 (ZNF281) has been identified to be involved in embryonic stem cell differentiation and tissue development. Also, ZNF281 was found in various types of cancers. However, its biological functions and clinical significance in pancreatic cancer remain elusive.

Aims

To explore the role of ZNF281 in pancreatic cancer cells proliferation and invasion.

Methods

ZNF281 expression was examined in public database Oncomine and cBioPortal. The correlation between ZNF281 and clinicopathological features was measured, and Kaplan–Meier method was used to measure the overall survival and recurrence-free survival in the TCGA cohort. Ectopic expression and knockdown of ZNF281 were performed to measure the impact on cell proliferation and invasion. Western blot and immunoprecipitation were further used to identify the ZNF281 interacting proteins. Topflash luciferase assay was used to detect the Wnt/β-catenin signaling activation.

Results

ZNF281 was predominantly up-regulated in pancreatic cancer tissues and significantly associated with advanced stage. Meanwhile, the high expression of ZNF281 indicated shorter overall survival and recurrence-free survival and ZNF281 could be an independent prognostic factor of pancreatic cancer. ZNF281 promoted cell proliferation and invasion in vitro. Mechanically, ZNF281 activated Wnt/β-catenin signaling and induced the downstream gene expression by directly binding with β-catenin and decreasing the polyubiquitination.

Conclusions

ZNF281 promotes pancreatic cancer cells proliferation and invasion by interacting and up-regulating β-catenin, highlighting the role of ZNF281 in pancreatic cancer progression.

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Prevalence and Predictors of Significant Fibrosis Among Subjects with Transient Elastography-Defined Nonalcoholic Fatty Liver Disease

Abstract

Background/Aims

Transient elastography (TE) can be used to assess the degree of liver fibrosis and steatosis. We investigated the prevalence and predictors of nonalcoholic fatty liver disease (NAFLD) with or without significant liver fibrosis in the general population.

Methods

A total of 3033 subjects without alcoholic or chronic viral liver diseases who underwent a medical health check-up including TE were recruited from April 2013 to August 2014. TE-defined NAFLD was defined as a controlled attenuation parameter of ≥250 dB/m, and significant liver fibrosis was defined as a liver stiffness (LS) value of ≥8 kPa.

Results

Overall, 1178 (42.9%) subjects had NAFLD. Subjects with NAFLD had significantly higher alanine aminotransferase (ALT) levels and a higher prevalence of parameters related to metabolic syndrome, such as high blood pressure, a high body mass index (BMI), glucose intolerance, and dyslipidemia than did subjects without NAFLD (all P < 0.05). Age, male gender, ALT level, serum albumin, BMI, diabetes, hypertriglyceridemia, and LS values independently showed positive associations with the presence of NAFLD (all P < 0.05). In addition, concomitant significant liver fibrosis was identified in 60 (5.1%) subjects with NAFLD, and its independent predictors were age [odds ratio (OR) 1.054], ALT level (OR 1.019), BMI (OR 1.217), and diabetes (OR 1.987) (all P < 0.05).

Conclusions

We found that the prevalence of subjects with NAFLD was high (42.9%), and 5.1% of them had concomitant significant liver fibrosis. The risk factors found in this study can help identify which subjects with NAFLD are vulnerable to fibrosis progression.

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Proteomic Analysis of Serum Amyloid A as a Potential Marker in Intestinal Behçet’s Disease

Abstract

Background/Aims

Data regarding biomarkers to understand disease pathogenesis and to assess disease activity of intestinal Behçet's disease (BD) are limited. Therefore, we aimed to investigate the differentially expressed proteins in sera from patients with intestinal BD and to search for biomarkers using mass spectrometry-based proteomic analysis.

Methods

Serum samples were pooled for the screening study, and two-dimensional electrophoresis (2-DE) was performed to characterize the proteins present in intestinal BD patients. Candidate protein spots were identified using matrix-assisted laser desorption/ionization tandem time-of-flight mass spectrometry (MALDI-TOF/TOF MS) and bioinformatic analysis. To validate the proteomic results, serum samples from an independent cohort were assessed by enzyme-linked immunosorbent assay.

Results

Pooled serum samples were used for 2-DE, and approximately 400 protein spots were detected in the sera of intestinal BD patients. Of the 22 differentially expressed proteins, 3 were successfully identified using MALDI-TOF/TOF MS. The three up-regulated proteins identified in the intestinal BD group included fibrin, apolipoprotein A-IV, and serum amyloid A (SAA). Serum SAA in intestinal BD patients (2.76 ± 2.50 ng/ml) was significantly higher than that in controls (1.68 ± 0.90 ng/ml, p = 0.007), which is consistent with the proteomic results. In addition, the level of IL-1β in patients with intestinal BD (8.96 ± 1.23 pg/ml) was higher than that in controls (5.40 ± 0.15 pg/ml, p = 0.009). SAA released by HT-29 cells was markedly increased by tumor necrosis factor-α (TNF-α) and lipopolysaccharides stimulation.

Conclusions

Our proteomic analysis revealed that SAA was up-regulated in intestinal BD patients.

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Primary Care and Hepatology Provider–Perceived Barriers to and Facilitators of Hepatitis C Treatment Candidacy and Adherence

Abstract

Background

Provider perceptions regarding barriers to and facilitators of hepatitis C (HCV) treatment initiation and adherence have not been fully evaluated in the interferon-free treatment era. New treatments have provided opportunities for non-specialists to treat HCV, underscoring the importance of understanding primary care provider (PCP) and specialist perspectives.

Methods

Based on qualitative sampling principles, 12 PCPs and 12 hepatology providers (HPs) from the VA Pittsburgh Healthcare System completed audio-recorded semi-structured interviews. Qualitative analysts coded perceived barriers and facilitators from the interviews with 100% double coding. Codes were thematized and analyzed using Atlas.ti.

Results

Key barriers to treatment described by HPs and PCPs included patients' substance use disorders, mental health, transportation availability, history of non-adherence, and concern about side effects. PCPs also focused on medication cost as a system-based barrier. The main facilitators of treatment initiation and adherence described by both HPs and PCPs were provider education and encouragement. HPs focused almost exclusively on provider-based facilitators, while PCPs noted patient-based facilitators including past adherence, media exposure to information about HCV medications, a desire to clear the virus, and positive feedback regarding treatment response.

Conclusions

Providers generally focused on perceived patient-level barriers to HCV treatment initiation and adherence, as well as provider-level facilitators; PCPs additionally noted patient preferences and system-level issues that guide decision making regarding treatment initiation. While HPs focused almost exclusively on provider-level facilitators, PCPs additionally focused on patient-level facilitators of treatment. These data provide novel insights and suggest focusing on patient, provider, and system-level strategies to further improve HCV treatment initiation and adherence.

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FFA3 Activation Stimulates Duodenal Bicarbonate Secretion and Prevents NSAID-Induced Enteropathy via the GLP-2 Pathway in Rats

Abstract

Background

Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO₃⁻ secretion. We thus investigated the effects of synthetic selective FFA3 agonists with consequent GLP-2 release on NSAID-induced enteropathy.

Methods

We measured duodenal HCO₃⁻ secretion in isoflurane-anesthetized rats in a duodenal loop perfused with the selective FFA3 agonists MQC or AR420626 (AR) while measuring released GLP-2 in the portal vein (PV). Intestinal injury was produced by indomethacin (IND, 10 mg/kg, sc) with or without MQC (1–10 mg/kg, ig) or AR (0.01–0.1 mg/kg, ig or ip) treatment.

Results

Luminal perfusion with MQC or AR (0.1–10 µM) dose-dependently augmented duodenal HCO₃⁻ secretion accompanied by increased GLP-2 concentrations in the PV. The effect of FFA3 agonists was inhibited by co-perfusion of the selective FFA3 antagonist CF3-MQC (30 µM). AR-induced augmented HCO₃⁻ secretion was reduced by iv injection of the GLP-2 receptor antagonist GLP-2(3-33) (3 nmol/kg), or by pretreatment with the cystic fibrosis transmembrane conductance regulator (CFTR) inhibitor CFTR_inh-172 (1 mg/kg, ip). IND-induced small intestinal ulcers were dose-dependently inhibited by intragastric administration of MQC or AR. GLP-2(3-33) (1 mg/kg, ip) or CF3-MQC (1 mg/kg, ig) reversed AR-associated reduction in IND-induced enteropathy. In contrast, ip injection of AR had no effect on enteropathy.

Conclusion

These results suggest that luminal FFA3 activation enhances mucosal defenses and prevents NSAID-induced enteropathy via the GLP-2 pathway. The selective FFA3 agonist may be a potential therapeutic candidate for NSAID-induced enteropathy.

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Conceptual Structure of Health Related Quality of Life for Persons with Traumatic Brain Injury: Confirmatory Factor Analysis of the TBI-QOL

Publication date: Available online 18 May 2017
Source:Archives of Physical Medicine and Rehabilitation
Author(s): Mark Sherer, Julia Maria Paul Poritz, David Tulsky, Pamela Kisala, Luis Leon-Novelo, Esther Ngan
ObjectiveTo determine the factor structure of the Traumatic Brain Injury – Quality of Life (TBI-QOL) measurement system.DesignObservational.Setting3 TBI Model Systems rehabilitation centers in the USParticipantsand Methods: 20 TBI-QOL item banks were administered to a sample of 504 community-dwelling adults with traumatic brain injury (TBI) as part of a study of TBI classification. A subsample of n=200 participants was randomly selected for exploratory factor analyses (EFA), while data from the remaining 304 participants were used for the confirmatory factor analysis (CFA). To examine a wide range of conceptual models, CFA were conducted on a total of 16 models, ranging from 1 to 7 factors.ResultsInitial EFA yielded support for a 5-factor model (negative emotion, cognitive impairment, functioning and participation, positive emotion, and pain). CFA results; however, indicated a 7-factor model including: physical function, physical symptoms, cognition, negative emotion, positive emotion, sense of self, and social participation (Model 16; Robust Fit Statistics RMSEA=0.063, SRMR=0.035, CFI=0.955, TLI=0.943, and BIC=40059.44).ConclusionsThe complex 7-factor model of the TBI-QOL provides a more nuanced framework for understanding health related quality of life for persons with TBI than the commonly used 3 factor model including physical health, mental health, and social health.



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Can an NTI-tss device be effective as a first-line therapy in patients with TMD myofascial pain?

Abstract

Objectives

This study was conducted to evaluate if integrating a nociceptive trigeminal inhibition–tension suppression system (NTI-tss) device with first-line therapy of myofascial pain, which includes guidance, assurance, counseling, and behavioral changes, would be more effective in alleviating symptoms.

Methods

This randomized controlled clinical trial included 40 patients who were clinically diagnosed with myofascial pain according to Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD). Patients were randomly divided into 2 groups: the first group comprised patients who received guidance, assurance, counseling, and behavioral changes; an NTI-tss device was integrated to this protocol in the second group.

Results

Both groups exhibited reduction in pain levels and improvement of jaw function compared with baseline values, but the difference was not significant.

Conclusion

Both groups demonstrated improvements in 6 weeks; however, the integration of NTI-tss device into the therapy protocol did not provide any additional benefit in relieving symptoms of myofascial pain.

This article is protected by copyright. All rights reserved.

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Determination of Occlusal Vertical Dimension for Complete Dentures Patients: An Updated Review

Abstract

Determination of the occlusal vertical dimension (OVD) is an integral part of complete dentures fabrication. Due to the lack of teeth, the clinician faces the challenge of how to accurately establish the OVD of the new denture. Therefore, the purpose of this review article was to present, discuss and critique the available methods used in determining the OVD for complete dentures patients. This review identified two main streams to determine the OVD: (1) pre-extraction methods and (2) post-extraction methods. For the pre-extraction methods, the OVD of the natural dentition is transferred to the new dentures mainly by intraoral measurements, profile tracing and cephalometric analysis. The post-extraction methods rely on mandibular rest position, facial esthetic appearance, swallowing pattern, craniofacial landmarks measurements, cephalometric analysis, phonetics and existing dentures. In general, all the available techniques have merits and are helpful for routine clinical use. However, they are empirical in nature, controversial and lack the scientific support. Further, there is no single accurate method for OVD determination. To overcome the limitations of the techniques, the clinician will benefit from applying combination of techniques to approximate the OVD.

This article is protected by copyright. All rights reserved.

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Observational study investigating tooth extraction and the shortened dental arch approach

Abstract

Background

The Shortened Dental Arch (SDA) provides a cost effective dentition, considering the population is aging and retaining teeth for longer.

Objective(s)

Observe the reasons and sites of tooth extraction, and assess the functional dentition over 15 years in dental practice.

Method

Subjects were recruited who required permanent tooth extractions between 2000-2015. The reasons for extractions were chosen from twelve extraction codes. Data was also collected for demographics, tooth position, root treated teeth and functional pairs remaining. Patient centred factors on tooth extraction and comments on chewing ability and aesthetics were recorded.

Results

Nine hundred and fifty one teeth were extracted in 900 patients. The mean age was 60 years (SD 20, SE 7, 95% CI 46,74). Reasons for extraction were periodontal disease (n=361, 38%), periapical infection (n=288, 34%) or tooth and tooth-root fractures (15%). Extractions included 201 (21%) second molars, 179 (19%) first molars, 152 (16%) second premolars, 95 (10%) first incisors, 86 (9%) second incisors, 76 (8%) canines and 67 (7%) first premolars. Following extractions, median functional pairs were 12, interquartile range (IQR) 19-7. Individuals with >10 functional pairs (60%, n=571) had no complaints with chewing ability or aesthetics.

Conclusions

Periodontal disease and periapical infection were the main causes for the extraction. First and second molars, followed by second premolars were the most commonly extracted teeth. The present study supports the SDA in creating a functional dentition, provided existing teeth and restorations are preserved/maintained and anterior aesthetic tooth replacement is ensured.

This article is protected by copyright. All rights reserved.

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Normalization of hemoglobin-based oxygen carrier-201 induced vasoconstriction: targeting nitric oxide and endothelin

Hemoglobin-based oxygen carrier (HBOC)-201 is a cell-free modified hemoglobin solution potentially facilitating oxygen uptake and delivery in cardiovascular disorders and hemorrhagic shock. Clinical use has been hampered by vasoconstriction in the systemic and pulmonary beds. Therefore, we aimed to 1) determine the possibility of counteracting HBOC-201-induced pressor effects with either adenosine (ADO) or nitroglycerin (NTG); 2) assess the potential roles of nitric oxide (NO) scavenging, reactive oxygen species (ROS), and endothelin (ET) in mediating the observed vasoconstriction; and 3) compare these effects in resting and exercising swine. Chronically instrumented swine were studied at rest and during exercise after administration of HBOC-201 alone or in combination with ADO. The role of NO was assessed by supplementation with NTG or administration of the eNOS inhibitor N-nitro-l-arginine. Alternative vasoactive pathways were investigated via intravenous administration of the ET_A/ET_B receptor blocker tezosentan or a mixture of ROS scavengers. The systemic and to a lesser extent the pulmonary pressor effects of HBOC-201 could be counteracted by ADO; however, dosage titration was very important to avoid systemic hypotension. Similarly, supplementation of NO with NTG negated the pressor effects but also required titration of the dose. The pressor response to HBOC-201 was reduced after eNOS inhibition and abolished by simultaneous ET_A/ET_B receptor blockade, while ROS scavenging had no effect. In conclusion, the pressor response to HBOC-201 is mediated by vasoconstriction due to NO scavenging and production of ET. Further research should explore the effect of longer-acting ET receptor blockers to counteract the side effect of hemoglobin-based oxygen carriers.

NEW & NOTEWORTHY Hemoglobin-based oxygen carrier (HBOC)-201 can disrupt hemodynamic homeostasis, mimicking some aspects of endothelial dysfunction, resulting in elevated systemic and pulmonary blood pressures. HBOC-201-induced vasoconstriction is mediated by scavenging nitric oxide (NO) and by upregulating endothelin (ET) production. Pressor effects can be prevented by adjuvant treatment with NO donors or direct vasodilators, such as nitroglycerin or adenosine, but dosages must be carefully monitored to avoid hypotension. However, hemodynamic normalization is more easily achieved via administration of an ET receptor blocker.

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Active shortening protects against stretch-induced force deficits in human skeletal muscle

Skeletal muscle contraction results from molecular interactions of myosin "crossbridges" with adjacent actin filament binding sites. The binding of myosin to actin can be "weak" or "strong," and only strong binding states contribute to force production. During active shortening, the number of strongly bound crossbridges declines with increasing shortening velocity. Forcibly stretching a muscle that is actively shortening at high velocity results in no apparent negative consequences, whereas stretch of an isometrically (fixed-length) contracting muscle causes ultrastructural damage and a decline in force-generating capability. Our working hypothesis is that stretch-induced damage is uniquely attributable to the population of crossbridges that are strongly bound. We tested the hypothesis that stretch-induced force deficits decline as the prevailing shortening velocity is increased. Experiments were performed on permeabilized segments of individual skeletal muscle fibers obtained from human subjects. Fibers were maximally activated and allowed either to generate maximum isometric force (F_o), or to shorten at velocities that resulted in force maintenance of 50% F_o or 2% F_o. For each test condition, a rapid stretch equivalent to 0.1 x optimal fiber length was applied. Relative to prestretch F_o, force deficits resulting from stretches applied during force maintenance of 100, 50, and 2% F_o were 23.2 ± 8.6, 7.8 ± 4.2, and 0.3 ± 3.3%, respectively (means ± SD, n = 20). We conclude that stretch-induced damage declines with increasing shortening velocity, consistent with the working hypothesis that the fraction of strongly bound crossbridges is a causative factor in the susceptibility of skeletal muscle to stretch-induced damage.

NEW & NOTEWORTHY Force deficits caused by stretch of contracting muscle are most severe when the stretch is applied during an isometric contraction, but prevented if the muscle is shortening at high velocity when the stretch occurs. This study indicates that velocity-controlled modulation of the number of strongly bound crossbridges is the basis for the observed relationship between stretch-induced muscle damage and prevailing shortening velocity.

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Reply to Drs. Van Breda et al.

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Clinical VO2peak is "part of the deal"

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Moderate and intense muscular exercises induce marked intramyocellular metabolic acidosis in sickle cell disease mice

Sickle cell disease (SCD) is associated with an impaired oxygen delivery to skeletal muscle that could alter ATP production processes. The present study aimed to determine the effects of sickle hemoglobin (HbS) on muscle pH homeostasis in response to exercise in homozygous (HbSS, n = 9) and heterozygous (HbAS, n = 10) SCD (Townes) mice in comparison to control (HbAA, n = 10) littermates. Magnetic resonance spectroscopy of phosphorus 31 enabled to measure intramuscular pH and phosphocreatine (PCr) concentration during rest-stimulation-recovery protocols at two different intensities. Maximal activity of some enzymes involved in muscle energetics and content of proteins involved in pH regulation were also investigated. HbSS mice presented a more pronounced exercise-induced intramuscular acidosis, whatever the intensity of exercise. Moreover, the depletion of PCr was also exacerbated in HbSS mice in response to intense exercise as compared with both HbAA and HbAS mice (P < 0.01). While no difference was observed concerning proteins involved in muscle pH regulation, the activity of enolase (a glycolytic enzyme) was higher in both HbSS and HbAS mice as compared with controls (P < 0.05). Interestingly, HbAS mice presented also metabolic impairments as compared with their control counterparts. This study has identified for the first time an exacerbated exercise-induced intramuscular acidosis in SCD mice.

NEW & NOTEWORTHY The main finding of the present study was that the exercise-induced intramuscular acidosis was systematically more pronounced in sickle cell disease (SCD) mice as compared with their control counterparts. This result is important since it has been demonstrated in vitro that acidosis can trigger hemoglobin polymerization. From that point of view, our results tend to support the idea that high-intensity exercise may increase the risk of hemoglobin polymerization in SCD.

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Oral N-acetylcysteine and exercise tolerance in mild chronic obstructive pulmonary disease

Heightened oxidative stress is implicated in the progressive impairment of skeletal muscle vascular and mitochondrial function in chronic obstructive pulmonary disease (COPD). Whether accumulation of reactive oxygen species contributes to exercise intolerance in the early stages of COPD is unknown. The purpose of the present study was to determine the effects of oral antioxidant treatment with N-acetylcysteine (NAC) on respiratory, cardiovascular, and locomotor muscle function and exercise tolerance in patients with mild COPD. Thirteen patients [forced expiratory volume in 1 s (FEV₁)-to-forced vital capacity ratio < lower limit of normal (LLN) and FEV₁ ≥ LLN) were enrolled in a double-blind, randomized crossover study to receive NAC (1,800 mg/day) or placebo for 4 days. Severe-intensity constant-load exercise tests were performed with noninvasive measurements of central hemodynamics (stroke volume, heart rate, and cardiac output via impedance cardiography), arterial blood pressure, pulmonary ventilation and gas exchange, quadriceps muscle oxygenation (near-infrared spectroscopy), and estimated capillary blood flow. Nine patients completed the study with no major adverse clinical effects. Although NAC elevated plasma glutathione by ~27% compared with placebo (P < 0.05), there were no differences in exercise tolerance (placebo: 325 ± 47 s, NAC: 336 ± 51 s), central hemodynamics, arterial blood pressure, pulmonary ventilation or gas exchange, locomotor muscle oxygenation, or capillary blood flow from rest to exercise between conditions (P > 0.05 for all). In conclusion, modulation of plasma redox status with oral NAC treatment was not translated into beneficial effects on central or peripheral components of the oxygen transport pathway, thereby failing to improve exercise tolerance in nonhypoxemic patients with mild COPD.

NEW & NOTEWORTHY Acute antioxidant treatment with N-acetylcysteine (NAC) elevated plasma glutathione but did not modulate central or peripheral components of the O₂ transport pathway, thereby failing to improve exercise tolerance in patients with mild chronic obstructive pulmonary disease (COPD).

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Muscle-specific and age-related changes in protein synthesis and protein degradation in response to hindlimb unloading in rats

Disuse is a potent inducer of muscle atrophy, but the molecular mechanisms driving this loss of muscle mass are highly debated. In particular, the extent to which disuse triggers decreases in protein synthesis or increases in protein degradation, and whether these changes are uniform across muscles or influenced by age, is unclear. We aimed to determine the impact of disuse on protein synthesis and protein degradation in lower limb muscles of varied function and fiber type in adult and old rats. Alterations in protein synthesis and degradation were measured in the soleus, medial gastrocnemius, and tibialis anterior (TA) muscles of adult and old rats subjected to hindlimb unloading (HU) for 3, 7, or 14 days. Loss of muscle mass was progressive during the unloading period, but highly variable (–9 to –38%) across muscle types and between ages. Protein synthesis decreased significantly in all muscles, except for the old TA. Atrophy-associated gene expression was only loosely associated with protein degradation as muscle RING finger-1, muscle atrophy F-box (MAFbx), and Forkhead box O1 expression significantly increased in all muscles, but an increase in proteasome activity was only observed in the adult soleus. MAFbx protein levels were significantly higher in the old muscles compared with adult muscles, despite the old having higher expression of microRNA-23a. These results indicate that adult and old muscles respond similarly to HU, and the greatest loss in muscle mass occurs in predominantly slow-twitch extensor muscles due to a concomitant decrease in protein synthesis and increase in protein degradation.

NEW & NOTEWORTHY In this study, we showed that age did not intensify the atrophy response to unloading in rats, but rather that the degree of atrophy was highly variable across muscles, indicating that changes in protein synthesis and protein degradation occur in a muscle-specific manner. Our data emphasize the importance of studying muscles of varying fiber-type and physiological function at multiple time points to fully understand the molecular mechanisms responsible for disuse atrophy.

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Exercise-induced dehydration alters pulmonary function but does not modify airway responsiveness to dry air in athletes with mild asthma

Local airway water loss is the main physiological trigger for exercise-induced bronchoconstriction (EIB). Our aim was to investigate the effects of whole body water loss on airway responsiveness and pulmonary function in athletes with mild asthma and/or EIB. Ten recreational athletes with a medical diagnosis of mild asthma and/or EIB completed a randomized, crossover study. Pulmonary function tests, including spirometry, whole body plethysmography, and diffusing capacity of the lung for carbon monoxide (Dl_CO), were conducted before and after three conditions: 1) 2 h of exercise in the heat with no fluid intake (dehydration), 2) 2 h of exercise with ad libitum fluid intake (control), and 3) a time-matched rest period (rest). Airway responsiveness was assessed 2 h postexercise/rest via eucapnic voluntary hyperpnea (EVH) to dry air. Exercise in the heat with no fluid intake induced a state of mild dehydration, with a body mass loss of 2.3 ± 0.8% (SD). After EVH, airway narrowing was not different between conditions: median (interquartile range) maximum fall in forced expiratory volume in 1 s was 13 (7–15)%, 11 (9–24)%, and 12 (7–20)% in dehydration, control, and rest conditions, respectively. Dehydration caused a significant reduction in forced vital capacity (300 ± 190 ml, P = 0.001) and concomitant increases in residual volume (260 ± 180 ml, P = 0.001) and functional residual capacity (260 ± 250 ml, P = 0.011), with no change in Dl_CO. Mild exercise-induced dehydration does not exaggerate airway responsiveness to dry air in athletes with mild asthma/EIB but may affect small airway function.

NEW & NOTEWORTHY This study is the first to investigate the effect of whole body dehydration on airway responsiveness. Our data suggest that the airway response to dry air hyperpnea in athletes with mild asthma and/or exercise-induced bronchoconstriction is not exacerbated in a state of mild dehydration. On the basis of alterations in lung volumes, however, exercise-induced dehydration appears to compromise small airway function.

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Combined long-term caffeine intake and exercise inhibits the development of diabetic nephropathy in OLETF rats

This study was performed to examine the effects of long-term caffeine-intake, with and without exercise, on the progression of diabetic nephropathy (DN) in an obese diabetic rat model. Thirty-two male Otsuka Long-Evans Tokushima fatty (OLETF) rats were assigned to sedentary (OLETF-Sed), exercise (OLETF-Ex), caffeine-intake (OLETF-Caf), and combined (OLETF-Caf + Ex) groups. Caffeine-intake groups were fed rat chow containing caffeine (90.7 ± 4.7 mg/kg/day). The OLETF-Ex and OLETF-Caf + Ex groups were able to run voluntarily at any time using a rotatory wheel. Body weight (BW) and blood pressure (BP) were measured weekly from 24 to 29 wk of age. Pre- and posttreatment serum glucose, insulin, and creatinine concentrations were measured, and a 24 h urine sample was collected for measurement of creatinine clearance (Ccr) and albumin excretion (UE_Alb). After treatment, the kidneys were removed for morphological analysis. The OLETF-Caf and OLETF-Caf + Ex groups exhibited no BP increase during the study. Both the caffeine-intake groups exhibited a significant increase in urine volume (UV), electrolyte excretion, and Ccr, and decreased UE_Alb, following treatment. Furthermore, no structural damage was observed in the kidneys of rats from either caffeine-intake group, whereas the OLETF-Sed and OLETF-Ex groups exhibited DN progression. This study demonstrates that caffeine-intake alone and/or combined with exercise significantly decreases BW and improves glucose intolerance, without the progression of DN. Further research should be performed to examine whether the quantities of caffeine contained in a normal human daily intake also have a protective effect against kidney damage.

NEW & NOTEWORTHY The present study showed that caffeine administration alone and/or combined with exercise results in an improvement of diabetic nephropathy (DN), including an increase in creatinine clearance and urinary Na excretion, a decrease in urinary protein excretion, and in renal morphological findings. To our knowledge, there are no other studies showing that caffeine administration inhibits DN progression.

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Equations for O2 and CO2 solubilities in saline and plasma: combining temperature and density dependences

Solubilities of respiratory gasses in water, saline, and plasma decrease with rising temperatures and solute concentrations. Henry's Law, C = α·P, states that the equilibrium concentration of a dissolved gas is solubility times partial pressure. Solubilities in the water of a solution depend on temperature and the content of other solutes. Blood temperatures may differ more than 20°C between skin and heart, and an erythrocyte will undergo that range as blood circulates. The concentrations of O₂ and CO₂ are the driving forces for diffusion, exchanges, and for reactions. We provide an equation for O₂ and CO₂ solubilities, α, that allows for continuous changes in temperature, T, and solution density, , in dynamically changing states:a(T, sol, , , β)=[1–⋅(sol–)β]⋅(C1⋅e–k1T+C2⋅e–k2T)

This two-exponential expression with a density scalar , and a density exponent β, accounts for solubility changes due to density changes of an aqueous solution. It fits experimental data on solubilities in water, saline, and plasma over temperatures from 20 to 40°C, and for plasma densities, _sol up to 1.020 g/ml with ~0.3% error. The amounts of additional bound O₂ (to Hb) and CO₂ (bicarbonate and carbamino) depend on the concentrations in the local water space and the reaction parameters. During exercise, solubility changes are large; both _sol and T change rapidly with spatial position and with time. In exercise hemoconcentration plasma, _sol exceeds 1.02, whereas T may range over 20°C. The six parameters for O₂ and the six for CO₂ are constants, so solubilities are calculable continuously as T and _sol change.

NEW & NOTEWORTHY Solubilities for oxygen and carbon dioxide are dependent on the density of the solution, on temperature, and on the partial pressure. We provide a brief equation suitable for hand calculators or mathematical modeling, accounting for these factors over a wide range of temperatures and solution densities for use in rapidly changing conditions, such as extreme exercise or osmotic transients, with better than 0.5% accuracy.

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Mechanisms of the deep, slow-wave, sleep-related increase of upper airway muscle tone in healthy humans

Upper airway muscle activity is reportedly elevated during slow-wave sleep (SWS) when compared with lighter sleep stages. To uncover the possible mechanisms underlying this elevation, we explored the correlation between different indices of central and reflex inspiratory drive, such as the changes in airway pressure and end-expiratory CO₂ and the changes in the genioglossus (GG) and tensor palatini (TP) muscle activity accompanying transitions from the lighter N2 to the deeper N3 stage of non-rapid eye movement (NREM) sleep in healthy young adult men. Forty-six GG and 38 TP continuous electromyographic recordings were obtained from 16 men [age: 20 ± 2.5 (SD) yr; body mass index: 22.5 ± 1.8 kg/m²] during 32 transitions from NREM stages N2 to N3. GG but not TP activity increased following transition into N3 sleep, and the increase was positively correlated with more negative airway pressure, increased end-tidal CO₂, increased peak inspiratory flow, and increased minute ventilation. None of these correlations was statistically significant for TP. Complementary GG and TP single motor unit analysis revealed a mild recruitment of GG units and derecruitment of TP units during the N2 to N3 transitions. These findings suggest that, in healthy individuals, the increased GG activity during SWS is driven primarily by reflex stimulation of airway mechanoreceptors and central chemoreceptors.

NEW & NOTEWORTHY The characteristic increase in the activity of the upper airway dilator muscle genioglossus during slow-wave sleep (SWS) in young healthy individuals was found to be related to increased stimulation of airway mechanoreceptors and central chemoreceptors. No evidence was found for the presence of a central SWS-specific drive stimulating genioglossus activity in young healthy individuals. However, it remains to be determined whether a central drive exists in obstructive sleep apnea patients.

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