Association between α1-antitrypsin and bronchiectasis in patients with humoral immunodeficiency receiving gammaglobulin infusions

Background

In patients with humoral immunodeficiency, the progression of bronchiectasis has been known to occur despite adequate gammaglobulin therapy and in the absence of recurrent infections. This observation suggests that factors other than gammaglobulin replacement might play a part in the prevention of lung damage in this population. α₁-Antitrypsin deficiency can be associated with bronchiectasis, a chronic inflammatory lung disease. The protective levels of α₁-antitrypsin and phenotype in preventing bronchiectasis have not been thoroughly studied in the immunodeficient population. We hypothesized that patients with humoral immunodeficiencies on gammaglobulin infusions and bronchiectasis have lower median levels, but not necessary “classically” deficient levels, of α₁-antitrypsin compared with those without bronchiectasis.

Radiographically guided shave margins may reduce lumpectomy re‐excision rates

Minimizing margin re‐excision optimizes patient care by providing appropriate oncologic resection and reducing costs. This study aims to assess margin positivity rate in two groups: shave margin based on gross specimen (control group, CG) vs shave margin based on intraoperative imaging (radiographic group, RG). A total of 182 patients who underwent lumpectomy for stage O‐III breast cancer at a single institution from January 2013 to January 2014 were evaluated. There was statistically significant decrease in margin re‐excision rate with intraoperative mammography but not with ultrasound. Surgeons are ideally equipped to use intraoperative imaging to guide margin excision, thus, improving care and reducing costs.     

Nociceptin inhibits gamma-aminobutyric acidergic inputs to cardiac parasympathetic neurons in the nucleus ambiguus.

Studies have shown that nociceptin, the endogenous ligand for the opioid receptor-like receptor (ORL(1)), modulates central control of cardiovascular activity. The nucleus ambiguus, an area containing cardiac parasympathetic neurons, contains both ORL(1) receptors and neurons that contain nociceptin itself. Although previous work has shown that nociceptin acts to increase parasympathetic outflow to the heart, the mechanisms by which this is achieved are unknown. In the present study, the effects of nociceptin on spontaneous gamma-aminobutyric acidergic (GABAergic) input to cardiac parasympathetic neurons (IPSCs) was examined. At 100 microM, nociceptin inhibited both the frequency (-35.6%) and the amplitude (-49.5%) of spontaneous GABAergic IPSCs in cardiac vagal neurons. Nociceptin also caused a novel postsynaptic inhibition of the responses evoked by exogenous application of GABA. These results indicate that nociceptin acts both on neurons precedent to cardiovascular neurons to decrease the activity of GABAergic neurons that synapse upon cardiovascular neurons and directly, inhibiting the postsynaptic currents evoked by GABA. This inhibition by nociceptin would increase parasympathetic outflow to the heart, thus providing a possible mechanism for nociceptin-induced bradycardia.     

GAA variants and phenotypes among 1,079 patients with Pompe disease: Data from the Pompe Registry

Identification of variants in the acid α‐glucosidase (GAA) gene in Pompe disease provides valuable insights and systematic overviews are needed. We report on the number, nature, frequency, and geographic distribution of GAA sequence variants listed in the Pompe Registry, a long‐term, observational program and the largest global repository of Pompe disease data. Variant information was reviewed and compared with publicly available GAA databases/resources. Among 1,079 eligible patients, 2,075 GAA variants (80 unique novel) were reported. Variants were listed by groups representing Pompe disease phenotypes. Patients were classified as Group A: Symptom onset ≤ 12 months of age with cardiomyopathy; Group B: Symptom onset ≤ 12 years of age (includes patients with symptom onset ≤ 12 months of age without cardiomyopathy); or Group C: Symptom onset > 12 years of age. Likely impact of novel variants was predicted using bioinformatics algorithms. Variants were classified by pathogenicity using ACMG guidelines. Data reported from the Pompe Registry provide new information about the distribution of GAA variants globally and across the clinical spectrum, add to the number and diversity of GAA variants registered in public databases through published data sharing, provide a first indication of the severity of novel variants, and assist in diagnostic practice and outcome prediction.     

Sucrose fatty acid esters suppress pancreatic secretion accompanied by peptide YY release in pancreatico-biliary diverted rats

Our previous study demonstrated that intestinal administration of triglycerides suppressed protein-induced increases in pancreatic exocrine secretion in pancreatico-biliary diverted (PBD) rats, though the mechanism has not been clarified. The present study was conducted to determine whether esterified fatty acids or free fatty acids are responsible for this suppression, and whether an esterified fatty acid stimulates secretion of a pancreatic inhibitory hormone, peptide YY (PYY). We examined the effects of cocoa butter or non-digestible sucrose fatty acid esters on protein-induced pancreatic secretion in conscious PBD rats whose bile-pancreatic juice was diverted from the proximal small intestine through a catheter. Intraduodenal administration of the protein guanidinated casein hydrolysate (HGC, 150 mg in 1 ml water) enhanced pancreatic protein and trypsin secretion. However, administration of HGC with cocoa butter (100 mg ml(-1)) partly suppressed the increase in pancreatic secretion, and HGC with a highly esterified sucrose fatty acid ester, F-10 (100 mg ml(-1)), completely suppressed it. The low-esterified, water-soluble sucrose fatty acid ester F-160 also completely inhibited protein-induced pancreatic secretion in the presence or absence of the lipase inhibitor orlistat.In anaesthetized PBD rats, intraduodenal administration of HGC with sucrose ester F-160 suppressed HGC-induced pancreatic secretion, and induced PYY secretion more strongly than HGC with sucrose. These results suggest that the esterified fatty acid itself stimulates PYY release in the distal intestine, thereby inhibiting protein-induced pancreatic secretion.     

Correlates of High-Risk and Low-Risk Alcohol Use among College Students in Kerala,India

This study describes the prevalence and correlates of alcohol use among college students in Ernakulam, Kerala State, India. A total of 5784 students from 58 colleges selected by stratified random sampling completed a questionnaire incorporating standardized instruments. The prevalence of lifetime alcohol use was 21.4% with a male predominance. Among users, low-risk, hazardous, and dependent use were 80.2%, 18.3% and 0.9% respectively. Initiation was mostly with friends (45.3%). Both low-risk and high-risk alcohol users (hazardous and dependent users), in comparison to abstainers, had higher odds of being older, non-Muslim, having a part-time job, using other substances, and exposure to sexual abuse. Students who reported low-risk use also had an urban background, more severe psychological distress and suicidal thoughts, while high-risk users had attention deficit hyperactivity disorder (ADHD) symptoms. Students who reported high-risk use compared to low-risk users had higher odds of having a part-time job, tobacco use, and ADHD symptoms. Alcohol use among college students is common, with both low- and high-risk drinking associated with significant morbidity. This study highlights the need to promote public health policies to target and prevent all patterns of alcohol use among young people.     

Investigation of associations between exposures to pesticides and testosterone levels in Thai farmers

We conducted a cross-sectional study to assess the relationship between pesticide exposures and testosterone levels in 133 male Thai farmers. Urine and serum samples were collected concurrently from participants. Urine was analyzed for levels of specific and nonspecific metabolites of organophosphates (OPs), pyrethroids, select herbicides, and fungicides. Serum was analyzed for total and free testosterone. Linear regression analyses revealed significant negative relationships between total testosterone and the herbicide 2,4-dichlorophenoxyacetic acid (2,4-D) after controlling for covariates (eg, age, BMI, smoking status). Positive significant associations were found between some OP pesticides and total testosterone. Due to the small sample size and the observational nature of the study, future investigation is needed to confirm our results and to elucidate the biological mechanisms.     

InVitro Evaluation of Optimal Inhalation Flow Patterns for Commercial Dry Powder Inhalers and Pressurized Metered Dose Inhalers With Human Inhalation Flow Pattern Simulator

This study aimed at developing a novel analytical method to identify optimal inhalation flow patterns for commercial dry powder inhalers (DPIs) and pressurized metered dose inhalers (pMDIs). As typical commercial DPI and pMDI, Pulmicort^® Turbuhaler^®, and Sultanol^® Inhaler were evaluated by an in vitro inhalation performance testing system with a flow pattern simulator. An 8-stage Andersen cascade impactor (ACI) or twin stage liquid impinger (TSLI) was applied to determine the inhalation performance. The peak flow rate (PFR) of the inhalation flow pattern was set from 15 to 80 L/min in reference to our previous study. From TSLI test results, a higher PFR improved the inhalation performance of the DPI, while the performance of the pMDI was less affected by the PFR. Conversely, from ACI test results, the pMDI performance decreased with a higher PFR, while the DPI followed a similar pattern as in the TSLI test results, because ACI is a finer aerodynamic classification apparatus than TSLI. These results suggested that our in vitro system using a human inhalation flow pattern simulator successfully detected different optimal inhalation patterns between DPI and pMDI. That is, the higher PFR is better for Pulmicort^® Turbuhaler^® (DPI). Conversely, lower PFR is desirable for Sultanol^® Inhaler (pMDI).