Androgen receptor signaling protects male mice from the development of immune response to peanut.

OBJECTIVES: Peanut (PN) allergy is a major public health concern. Recent research has brought clarity about how individuals become sensitized to PN allergen with routes known through the skin, as well as the airway. Still unclear, however, is the role of sex hormones on the development of allergic immune responses to PN. This study examines the role of androgen receptor (AR) signaling in regulating PN-specific immune responses. METHODS: We utilized a 4-week inhalation mouse model of PN allergy that is known to drive the production of PN-specific antibodies and elicit systemic anaphylaxis following PN challenge. Wildtype (WT) male, female, and androgen receptor-deficient testicular feminization mutant (ARTfm) male mice were examined using this model to document sex differences in PN allergy. To determine if sex differences also existed in the cellular immune response, this study utilized a 3-day inhalation mouse model of PN to examine the response of group 2 innate lymphoid cells (ILC2s). WT male and female mice were examined using this model to document sex differences in ILC2 response within the lungs. RESULTS: AR use is critical in regulating PN-specific antibody levels. We found that ARTfm males have a higher antibody response and significantly worse anaphylactic response following PN challenge relative to WT males. WT males also exhibit a less severe anaphylactic response compared to ARTfm male and female mice. Lastly, we discovered that lung ILC2s from female mice respond more robustly to PN compared to ILC2s within WT male mice. CONCLUSIONS: Taken together, this study suggests that male sex hormones, namely androgens, negatively regulate allergic immune responses to PN.

Understanding sex differences in the allergic immune response to food.

Food allergies are of great public health concern due to their rising prevalence. Our understanding of how the immune system reacts to food remains incomplete. Allergic responses vary between individuals with food allergies. This variability could be caused by genetic, environmental, hormonal, or metabolic factors that impact immune responses mounted against allergens found in foods. Peanut (PN) allergy is one of the most severe and persistent of food allergies, warranting examination into how sensitization occurs to drive IgE-mediated allergic reactions. In recent years, much has been learned about the mechanisms behind the initiation of IgE-mediated food allergies, but additional questions remain. One unresolved issue is whether sex hormones impact the development of food allergies. Sex differences are known to exist in other allergic diseases, so this poses the question about whether the same phenomenon is occurring in food allergies. Studies show that females exhibit a higher prevalence of atopic conditions, such as allergic asthma and eczema, relative to males. Discovering such sex differences in allergic diseases provide a basis for investigating the mechanisms of how hormones influence the development of IgE-mediated reactions to foods. Analysis of existing food allergy demographics found that they occur more frequently in male children and adult females, which is comparable to allergic asthma. This paper reviews existing allergic mechanisms, sensitization routes, as well as how sex hormones may play a role in how the immune system reacts to common food allergens such as PN.

Gallstone Ileus: Uncommon Presentation Followed by Less Common Spontaneous Resolution.

Gallstone ileus is a rare but significant cause of bowel obstruction. An 82-year-old female was admitted to the hospital with abdominal pain and was initially treated for a possible urinary tract infection. Following a surgical review and based on history, clinical examination as well as radiological findings, a diagnosis of gallstone ileus was made. The patient was prepared for surgery; however, whilst awaiting theatre, she spontaneously passed the obstructing gallstone with full resolution of bowel obstruction symptoms. The usual treatment for gallstone ileus is surgical management with an enterolithotomy; nevertheless, this case highlights the importance of close monitoring and adapting a management plan to fit an evolving clinical scenario.

Neutrophil-to-lymphocyte ratio predicts acute appendicitis and distinguishes between complicated and uncomplicated appendicitis: A systematic review and meta-analysis.

OBJECTIVES: to investigate whether Neutrophil-to-lymphocyte ratio (NLR) can predict acute appendicitis and whether it can distinguish between uncomplicated and complicated appendicitis. METHODS: A search of electronic information sources was conducted to identify all studies reporting NLR in patients with clinical suspicion or confirmed diagnosis of acute appendicitis. We considered two comparisons:1) appendicitis versus no appendicitis; 2) uncomplicated appendicitis versus complicated appendicitis. ROC curve analysis was performed to determine cut-off values of NLR for appendicitis and complicated appendicitis. RESULTS: Seventeen studies, enrolling 8,914 patients were included. NLR of 4.7 was cut-off value for appendicitis with sensitivity of 88.89% and specificity of 90.91% with AUC of 0.96. NLR of 8.8 was cut-off value for complicated appendicitis with sensitivity of 76.92% and specificity 100% with AUC of 0.91. NLR >4.7 was predictor of acute appendicitis (OR:128,P < 0.0001) and, NLR >8.8 was predictor of complicated appendicitis (OR:43,P < 0.0001). CONCLUSIONS: NLR predicts both diagnosis and severity of appendicitis. This may have implications for prioritising cases for surgery, for monitoring conservatively treated patients and for patients who do not routinely undergo CT scan (pregnant or paediatric patients).

A validated novel preoperative index to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology: A cohort study.

AIMS: To investigate whether an intraperitoneal contamination index (ICI) derived from combined preoperative levels of C-reactive protein, lactate, neutrophils, lymphocytes and albumin could predict the extent of intraperitoneal contamination in patients with acute abdominal pathology. METHODS: Patients aged over 18 who underwent emergency laparotomy for acute abdominal pathology between January 2014 and October 2018 were randomly divided into primary and validation cohorts. The proposed intraperitoneal contamination index was calculated for each patient in each cohort. Receiver operating characteristic curve analysis was performed to determine discrimination of the index and cut-off values of preoperative intraperitoneal contamination index that could predict the extent of intraperitoneal contamination. RESULTS: Overall, 468 patients were included in this study; 234 in the primary cohort and 234 in the validation cohort. The analyses identified intraperitoneal contamination index of 24.77 and 24.32 as cut-off values for purulent contamination in the primary cohort (area under the curve (AUC): 0.73, P < 0.0001; sensitivity: 84%, specificity: 60%) and validation cohort (AUC: 0.83, P < 0.0001; sensitivity: 91%, specificity: 69%), respectively. Receiver operating characteristic curve analysis also identified intraperitoneal contamination index of 33.70 and 33.41 as cut-off values for feculent contamination in the primary cohort (AUC: 0.78, P < 0.0001; sensitivity: 87%, specificity: 64%) and validation cohort (AUC: 0.79, P < 0.0001; sensitivity: 86%, specificity: 73%), respectively. CONCLUSIONS: As a predictive measure which is derived purely from biomarkers, intraperitoneal contamination index may be accurate enough to predict the extent of intraperitoneal contamination in patients with acute abdominal pathology and to facilitate decision-making together with clinical and radiological findings.

Oestrogen and androgen receptor activation contribute to the masculinisation of oxytocin receptors in the bed nucleus of the stria terminalis of rats.

Oxytocin (OT) often regulates social behaviours in sex-specific ways, and this may be a result of sex differences in the brain OT system. Adult male rats show higher OT receptor (OTR) binding in the posterior bed nucleus of the stria terminalis (pBNST) than adult female rats. In the present study, we investigated the mechanisms that lead to this sex difference. First, we found that male rats have higher OTR mRNA expression in the pBNST than females at postnatal day (P) 35 and P60, which demonstrates the presence of the sex difference in OTR binding density at message level. Second, the sex difference in OTR binding density in the pBNST was absent at P0 and P3, but was present by P5. Third, systemic administration of the oestrogen receptor (ER) antagonist fulvestrant at P0 and P1 dose-dependently reduced OTR binding density in the pBNST of 5-week-old male rats, but did not eliminate the sex difference in OTR binding density. Fourth, pBNST-OTR binding density was lower in androgen receptor (AR) deficient genetic male rats compared to wild-type males, but higher compared to wild-type females. Finally, systemic administration of the histone deacetylase inhibitor valproic acid at P0 and P1 did not alter pBNST-OTR binding density in 5-week-old male and female rats. Interestingly, neonatal ER antagonism, AR deficiency, and neonatal valproic acid treatment each eliminated the sex difference in pBNST size. Overall, we demonstrate a role for neonatal ER and AR activation in setting up the sex difference in OTR binding density in the pBNST, which may underlie sexual differentiation of the pBNST and social behaviour.

Use of combined laboratory and ultrasonography results to select patients for biliary tract imaging or intervention: a retrospective cohort study.

AIM: To determine whether combined laboratory and ultrasonography results can be used to select patients for biliary tract imaging (BTI) or intervention. BACKGROUND: Despite ongoing research, selection of patients with suspected CBD stone (CBDS) for BTI or direct intervention without imaging is still a subject of debate. METHODS: Patients aged≥18 with symptomatic gallstone disease (SGD) who underwent MRCP over 3 years (2014-2017) were divided into the following cohorts: Group A: Normal liver enzymes with normal CBD diameter; Group B: Normal liver enzymes with dilated CBD; Group C: Isolated rise of liver enzymes with normal CBD diameter; Group D: Isolated rise of liver enzymes with dilated CBD; Group E: Hyperbilirubinemia with normal CBD diameter; Group F: Hyperbilirubinemia with dilated CBD. Binary logistic regression models were constructed for analyses. RESULTS: Overall, 1022 patients were included. The frequency of CBDS was 7.2% in Group A; 3.8% in Group B; 6.3% in Group C; 22% in Group D; 24.2% in Group E; 47.4% in Group F. Hyperbilirubinemia with normal CBD (OR:1.52,P=0.010) and hyperbilirubinemia with dilated CBD (OR:5.12,P<0.001) independently predicted CBDS. Normal or isolated rise of liver enzymes with or without dilated CBD did not predict CBDS. Combined laboratory and ultrasonography had positive predictive value and negative predictive value of up to 47.37% and 100%, respectively. CONCLUSION: Patients with isolated rise of liver enzymes or hyperbilirubinemia with or without dilated CBD should undergo BTI prior to ERCP. Direct ERCP could be preserved for patients with high suspicion of CBDS where clinical features do not allow waiting for BTI.

Impact of Toupet Versus Nissen Fundoplication on Dysphagia in Patients With Gastroesophageal Reflux Disease and Associated Preoperative Esophageal Dysmotility: A Systematic Review and Meta-Analysis.

BACKGROUND: Controversy exists regarding the best surgical approach for the management of gastroesophageal reflux disease (GORD) and associated preoperative esophageal dysmotility. Our aim was to conduct a systematic review and meta-analysis to compare the outcomes of Toupet fundoplication (TF) and Nissen fundoplication (NF) in patients with GORD and coexistent preoperative esophageal dysmotility. METHODS: We conducted a systematic search of electronic information sources, including MEDLINE, EMBASE, CINAHL, CENTRAL, ClinicalTrials.gov , and bibliographic reference lists. We applied a combination of free text search and controlled vocabulary search adapted to thesaurus headings, search operators, and limits in each of the above-mentioned databases. Postoperative dysphagia and improvement in dysphagia were primary outcome parameters. RESULTS: We identified 3 randomized controlled trials and 1 observational study reporting a total of 220 patients, of whom 126 underwent TF and the remaining 94 patients had NF. Despite the existence of significantly higher preoperative dysphagia in the TF group (29.3% vs 4.2%, P = .05), TF was associated with significantly lower postoperative dysphagia (odds ratio [OR] = 0.31, P = .002) with low between-study heterogeneity ( I2 = 11%, P = .34), and significantly higher improved dysphagia (OR = 10.32, P < .0001) with moderate between-study heterogeneity ( I2 = 31%, P = .23) compared with NF. CONCLUSION: TF may be associated with significantly lower postoperative dysphagia than NF in patients with GORD and associated preoperative esophageal dysmotility. However, no definite conclusions can be drawn as the best available evidence comes mainly from a limited number of heterogeneous randomized controlled trials. Future studies are encouraged to include patients with similar preoperative dysphagia status and report the outcomes with respect to recurrence of acid reflux symptoms.

Sex and laterality differences in medial amygdala neurons and astrocytes of adult mice.

The posterodorsal aspect of the medial amygdala (MePD) in rats is sexually dimorphic, being larger and containing more and larger neurons in males than in females. It is also highly lateralized, with the right MePD larger than the left in both sexes, but with the smaller left MePD actually containing more and larger neurons than the larger right. Astrocytes are also strikingly sexually differentiated, with male-biased numbers and lateralized favoring the right in the rat MePD. However, comparable information is scant for mice where genetic tools offer greater experimental power. Hence, we examined the MePD from adult male and female C57Bl/6(J) mice. We now report that the MePD is larger in males than in females, with the MePD in males containing more astrocytes and neurons than in females. However, we did not find sex differences in astrocyte complexity or overall glial number nor effects of laterality in either measure. While the mouse MePD is generally less lateralized than in rats, we did find that the sex difference in astrocyte number is only on the right because of a significant lateralization in females, with significantly fewer astrocytes on the right than the left but only in females. A sex difference in neuronal soma size favoring males was also evident, but only on the left. Sex differences in the number of neurons and astrocytes common to both rodent species may represent core morphological features that critically underlie the expression of sex-specific behaviors that depend on the MePD. J. Comp. Neurol. 524:2492-2502, 2016. © 2016 Wiley Periodicals, Inc.

Female meadow voles, Microtus pennsylvanicus, respond differently to the scent marks of multiple male conspecifics.

Many nonhuman animals are capable of discriminating a group or entity containing more objects from one containing less of the same objects. The capacity for making judgments of numerousness may also allow individuals to discriminate between potential mates. Female meadow voles (Microtus pennsylvanicus) may use judgments of relative numerousness to distinguish between potential suitors by selecting males that signal their interest by depositing more scent marks relative to other males. We used a familiarization-discrimination paradigm in the absence of training to test the hypothesis that female voles will discriminate between the different numerosities of scent marks of two male conspecifics that are similar in features of their phenotype and quality. During the exposure phase, we presented female voles with different ratios of feces scent marks from two males. During the test phase, we presented females with a single, fresh fecal scent mark from each of the two male donors, whose marks they had previously encountered during the exposure phase. In both phases, females spent more time investigating the scent mark(s) of the male that deposited more scent marks than that of the male that deposited fewer scent marks provided the difference in the ratio of scent marks provided by the male donors in the exposure phase was ≥2. Our results are consistent with studies on a variety of taxa, suggesting that numerosity discriminations are evolutionarily ancient and spontaneously available to nonhuman animals and humans.

Effects of food availability on proceptivity: a test of the reproduction at all costs and metabolic fuels hypotheses.

Proceptive behaviours are used by animals to indicate interest in opposite-sex conspecifics. These behaviours can be affected by an individual's nutritional status. Two mutually exclusive hypotheses have been proposed to account for the effects of food availability on reproduction. These are the metabolic fuels hypothesis and the reproduction at all costs hypothesis. It is not known if food availability affects proceptive behaviours such as scent marking, over-marking, and self-grooming. In this study, we tested the hypothesis that food-deprived and nonfood-deprived meadow voles, Microtus pennsylvanicus, differ in the number of scent marks they deposit, the proportion of over-marks they deposit, and the amount of time they spend self-grooming when they encounter the scent marks of opposite-sex conspecifics. We tested this hypothesis by exposing meadow voles that either had continuous access to food or were food-deprived for either 6 hours or 24 hours to the scent marks of an opposite-sex conspecific. Due to differences in the natural history of male and female meadow voles, we predicted that female voles' behaviour will best be explained by the metabolic fuels hypothesis whereas males' behaviour will best be explained by the reproduction at all costs hypothesis. We found that both male and female voles deprived of food for either 6 hours or 24 hours spent less time self-grooming compared to nonfood-deprived voles. However, food availability did not affect the scent marking and over-marking behaviour of male and female voles. Differences in the effects of food availability on these proceptive behaviours are discussed within the context of the natural history of meadow voles.