Apparent Sex Difference Research Articles

The mediation effects of malalignment on the relation of sex to the risk of incidence tibiofemoral osteoarthritis

ObjectiveTo investigate to what extent the higher risk of tibiofemoral radiographic osteoarthritis (TFROA) in females vs. males can be explained by knee malalignment. DesignUsing data from Multicenter Osteoarthritis Study (MOST) and Osteoarthritis Initiative (OAI), we examined the relation of sex to the incident medial and lateral TFROA and performed mediation analyses to assess to what extent varus and valgus malalignments account for sex differences in the incident medial or lateral TFROA. ResultsOf the 3,462 knees without medial and lateral TFROA in MOST, the 7-year risks of medial and lateral TFROA were 16.9% and 10.0% in females, and 15.8% and 4.2% in males, respectively. Females had 2.31-fold (95% CI: 1.73 to 3.08) higher incident lateral TFROA than males, and the relative risk (RR) of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.15 (95% CI:1.09 to 1.20), accounting for 23% of its total effect on lateral TFROA. In OAI (n=3,095 knees), females had 1.54-fold (95% CI:1.15 to 2.04) higher incident lateral TFROA than males, and RR of the indirect effect of sex on lateral TFROA through valgus malalignment was 1.10 (95% CI:1.04 to 1.21), accounting for 26% of its total effect on lateral TFROA. No apparent sex difference in the incident medial TFROA was found in MOST (RR=1.05, 95% CI: 0.89 to 1.25) or OAI (RR=1.02, 95% CI: 0.84 to 1.19). ConclusionFemales had a higher risk of developing lateral TFROA than males; however, valgus malalignment only modestly explained such a difference.

No sex differences in time-to-task failure and neuromuscular patterns of response during submaximal, bilateral, isometric leg extensions.

In general, it has been suggested that females are more fatigue-resistant than males, with the magnitude of difference being most pronounced during low-intensity sustained contractions. However, the mechanisms for the apparent sex difference have not yet been fully elucidated in the literature. This study aimed to examine sex-related differences in fatigability and patterns of neuromuscular responses for surface electromyographic (sEMG) and mechanomyographic (sMMG) amplitude and frequency (MPF) characteristics during a sustained submaximal bilateral, isometric leg extension muscle action. A sample of 20 young recreationally active males and females with previous resistance training experience performed a sustained, submaximal, bilateral isometric leg extension until task failure. Time-to-task failure was compared using a nonparametric bootstrap of the 95% confidence interval for the mean difference between males and females. Additionally, patterns of response for sEMG and sMMG amplitude and MPF of the dominant limb were examined using linear mixed effect models. There were no differences in time-to-task failure between males and females. Additionally, neuromuscular responses revealed similar patterns of responses between males and females. Interestingly, sEMG amplitude and sMMG amplitude and MPF all revealed non-linear responses, while sEMG MPF demonstrated linear responses. These data revealed that time-to-task failure was not different between males and females during sustained submaximal bilateral, isometric leg extension. Interestingly, the parallel, non-linear, increases in sEMG and sMMG amplitude may indicate fatigue induced increases in motor unit recruitment, while the parallel decreases in sMMG MPF may be explained by the intrinsic properties of later recruited motor units, which may have inherently lower firing rates than those recruited earlier.

Parental role-modeling on 24-hour movement behaviors among preschoolers during the COVID-19 pandemic.

Little is known about the association between parents' and children's 24-h movement behaviors during the pandemic. This cross-sectional study examined the association between the 24-h movement behaviors of parents and their preschoolers and investigated sex differences in this association. A total of 1740 preschoolers (4.5 ± 0.8 years old, 50.3% boys) and their parents (35.4 ± 4.9 years old, 24.3% males) in China participated in this study and provided valid and complete data. Parents completed an online survey or a written questionnaire in the period between October and December 2020. Preschoolers' and parents' movement behaviors (physical activity [PA], sedentary behavior [SB], screen time, and sleep) and demographic information were reported by the parents. Generalized linear models and logistic regression models were performed. Positive associations were found between parents' and preschoolers' moderate-to-vigorous intensity PA (β = 0.28; 95% confidence interval [CI]: 0.20, 0.36), total PA (β = 0.21; 95% CI: 0.17, 0.24), and sleep (β = 0.05; 95% CI: 0.03, 0.06) with no apparent sex difference. No significant association was found between parents' and preschoolers' SB or screen time. Girls were more likely to meet all three 24-h movement guidelines when their parents met them (odds ratio = 2.38; 95% CI: 1.42, 4.01), but the relationship was not significant for boys. Parental role-modeling was positively associated with children's PA and sleep. This finding suggests that supporting parents' movement behaviors has the potential to promote a healthy lifestyle among preschoolers.

Sex differences in zymosan-induced behavioral visceral hypersensitivity and colorectal afferent sensitization.

Sex differences in visceral nociception have been reported in clinical and preclinical studies, but the potential differences in sensory neural encoding of the colorectum between males and females are not well understood. In this study, we systematically assessed sex differences in colorectal neural encoding by conducting high-throughput optical recordings in intact dorsal root ganglia (DRGs) from control and visceral hypersensitive mice. We found an apparent sex difference in zymosan-induced behavioral visceral hypersensitivity: enhanced visceromotor responses to colorectal distension were observed only in male mice, not in female mice. In addition, a higher number of mechanosensitive colorectal afferents were identified per mouse in the zymosan-treated male group than in the saline-treated male group, whereas the mechanosensitive afferents identified per mouse were comparable between the zymosan- and saline-treated female groups. The increased number of identified afferents in zymosan-treated male mice was predominantly from thoracolumbar (TL) innervation, which agrees with the significant increase in the TL afferent proportion in the zymosan group as compared with the control group in male mice. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline- and zymosan-treated groups. Our results revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity, which could drive differential clinical symptoms in male and female patients.NEW & NOTEWORTHY We used high-throughput GCaMP6f recordings to study 2,275 mechanosensitive colorectal afferents in mice. Our results revealed significant sex differences in the zymosan-induced behavioral visceral hypersensitivity, which were present in male but not female mice. Male mice also showed sensitization of colorectal afferents in the thoracolumbar pathway, whereas female mice did not. These findings highlight sex differences in sensory neural anatomy and function of the colorectum, with implications for sex-specific therapies for treating visceral pain.

Effects of a school-based lifestyle intervention on ideal cardiovascular health in Chinese children and adolescents: a national, multicentre, cluster-randomised controlled trial

BackgroundThe prevalence of ideal cardiovascular health among Chinese children and adolescents is alarmingly low. We aimed to examine whether a school-based lifestyle intervention against obesity would improve ideal cardiovascular health. MethodsIn this cluster-randomised controlled trial, we included and randomly assigned schools from the seven regions of China to intervention or control (1:1), stratified by province and school grade (grades 1–11; ages 7–17 years). Randomisation was done by an independent statistician. The 9-month intervention consisted of school promotion for diet, exercise, and self-monitor of obesity-related behaviours and the control group was no promotion. The primary outcome, assessed at both baseline and 9 months, was ideal cardiovascular health (six or more ideal cardiovascular health behaviours [non-smoking, BMI, physical activity, and diet] and factors [total cholesterol, blood pressure, and fasting plasma glucose]). We did intention-to-treat analysis and multilevel modelling. This study was approved by the ethics committee of Peking University, Beijing, China (ClinicalTrials.gov, NCT02343588). Findings30 629 students in the intervention group and 26 581 students in the control group from 94 schools with any follow-up cardiovascular health measures were analysed. At follow-up, 22·0% (1139/5186) of the intervention group and 17·5% (601/3437) in the control group met ideal cardiovascular health. Overall, the intervention was associated with ideal cardiovascular health behaviours (three or more; odds ratio 1·15; 95% CI 1·02–1·29), but not other ideal cardiovascular health metrics after adjusting for covariates. The intervention had higher effects on ideal cardiovascular health behaviours in primary school students aged 7–12 years (1·19; 1·05–1·34) than secondary school students aged 13–17 years (p<0·0001), with no apparent sex difference (p=0·58). The intervention protected senior students aged 16–17 years from smoking (1·23; 1·10–1·37) and improved ideal physical activity in primary school students (1·14; 1·00–1·30) but was associated with lower odds of ideal total cholesterol in primary school boys (0·73; 0·57–0·94). InterpretationThis school-based intervention, focused on diet and exercise, was effective in improving ideal cardiovascular health behaviours in Chinese children and adolescents. Early intervention might benefit cardiovascular health over the life course. FundingThe Special Research Grant for Non-profit Public Service of the Ministry of Health of China (201202010) and Guangdong Provincial Natural Science Foundation (2021A1515010439).

Colitis Induces Sex-Specific Intestinal Transcriptomic Responses in Mice.

There are significant sex differences in colorectal cancer (CRC), including in incidence, onset, and molecular characteristics. Further, while inflammatory bowel disease (IBD) is a risk factor for CRC in both sexes, men with IBD have a 60% higher risk of developing CRC compared to women. In this study, we investigated sex differences during colitis-associated CRC (CAC) using a chemically induced CAC mouse model. The mice were treated with azoxymethane (AOM) and dextran sodium sulfate (DSS) and followed for 9 and 15 weeks. We performed RNA-sequencing of colon samples from males (n = 15) and females (n = 15) to study different stages of inflammation and identify corresponding transcriptomic sex differences in non-tumor colon tissue. We found a significant transcriptome response to AOM/DSS treatment in both sexes, including in pathways related to inflammation and cell proliferation. Notably, we found a stronger response in males and that male-specific differentially expressed genes were involved in NFκB signaling and circadian rhythm. Further, an overrepresented proportion of male-specific gene regulations were predicted to be targets of Stat3, whereas for females, targets of the glucocorticoid receptor (Gr/Nr3c1) were overrepresented. At 15 weeks, the most apparent sex difference involved genes with functions in T cell proliferation, followed by the regulation of demethylases. The majority of sex differences were thus related to inflammation and the immune system. Our novel data, profiling the transcriptomic response to chemically induced colitis and CAC, indicate clear sex differences in CRC initiation and progression.

Effect of hyperglycaemia in combination with moxifloxacin on cardiac repolarization in male and female patients with type I diabetes

BackgroundPatients with Type 1 diabetes mellitus have been shown to be at a two to ten-fold higher risk of sudden cardiac death (SCD) (Svane et al., Curr Cardiol 2020; 22:112) than the general population, but the underlying mechanism is unclear. Hyperglycaemia is a recognised cause of QTc prolongation; a state patients with type 1 diabetes are more prone to, potentially increasing their risk of ventricular arrhythmia. Understanding the QTc prolongation effect of both hyperglycaemia and the concomitant additive risk of commonly prescribed QTc-prolonging drugs such as Moxifloxacin may help to elucidate the mechanism of sudden cardiac death in this cohort. This single-blinded, placebo-controlled study investigated the extent to which hyperglycaemia prolongs the QTc in controlled conditions, and the potential additive risk of QTc-prolonging medications.Methods21 patients with type 1 diabetes mellitus were enrolled to a placebo-controlled crossover study at a single clinical trials unit. Patients underwent thorough QTc assessment throughout the study. A ‘hyperglycaemic clamp’ of oral and intravenous glucose was administered with a target blood glucose of > 25 mM and maintained for 2 h on day 1 and day 3, alongside placebo on day 1 and moxifloxacin on day 3. Day 2 served as a control day between the two active treatment days.Thorough QTc assessment was conducted at matched time points over 3 days, and regular blood sampling was undertaken at matched time intervals for glucose levels and moxifloxacin exposure.ResultsConcentration-effect modelling showed that acute hyperglycaemia prolonged the QTc interval in female and male volunteers with type 1 diabetes by a peak mean increase of 13 ms at 2 h. Peak mean QTc intervals after the administration of intravenous Moxifloxacin during the hyperglycaemic state were increased by a further 9 ms at 2 h, to 22 ms across the entire study population. Regression analysis suggested this additional increase was additive, not exponential.Hyperglycaemia was associated with a significantly greater mean QTc-prolonging effect in females, but the mean peak increase with the addition of moxifloxacin was the same for males and females. This apparent sex difference was likely due to the exclusive use of basal insulin in the male patients, which provided a low level of exogenous insulin during the study assessments thereby mitigating the effects of hyperglycaemia on QTc. This effect was partially overcome by Moxifloxacin administration, suggesting both hyperglycaemia and moxifloxacin prolong QTc by different mechanisms, based on subinterval analysis.ConclusionsHyperglycaemia was found to be a significant cause of QTc prolongation and the additional effect of a QTc-prolonging positive control (moxifloxacin) was found to be additive. Given the high risk of sudden cardiac death in type 1 diabetes mellitus, extra caution should be exercised when prescribing any medication in this cohort for QTc effects, and further research needs to be undertaken to elucidate the exact mechanism underlying this finding and explore the potential prescribing risk in diabetes.Trial RegistrationNCT number: NCT01984827.Graphical abstract

SPARC: Sex difference in colorectal afferent sensitization in zymosan‐induced visceral hypersensitivity as revealed by high‐throughput GCaMP recordings in thoracolumbar and lumbosacral DRG

Female patients with irritable bowel syndrome (IBS) report more intense visceral pain sensation than male patients. Female rats show more sensitive and cycle‐dependent visceromotor responses (VMR) to graded colorectal distension (CRD). Both clinical psychophysical evidence and preclinical behavioral data support an apparent sex difference in visceral nociception. However, very little is known regarding the potential differences in sensory neural encoding of distal colon and rectum (colorectum) between males and females. In this study, we systematically assessed the sex difference in colorectal neural encoding by conducting high‐throughput optical recordings in intact dorsal root ganglia (DRG) from control and visceral hypersensitive mice. We crossbred GCaMP6f mice with VGLUT2‐Cre mice to express GCamP6f gene in most colorectal sensory neurons. Mice receiving intracolonic treatment of zymosan (30mg/mL, 0.2mL) for three consecutive days developed behavioral visceral hypersensitivity as validated by enhanced VMR to CRD. We then harvested the colorectum with pelvic nerve, lumbar splanchnic nerve and T12 to S1 DRG in continuity in an ex vivo preparation for GCaMP6f recordings. A total of 2275 colorectal afferents were characterized from both sexes in control and zymosan‐treated groups. DRG neurons responding to either colorectal distension (15, 30, 45 and 60 mmHg) and/or mucosal shearing (20‐30 mL/min) were functionally categorized into four classes: mucosal, muscular‐mucosal and high‐ and low‐threshold muscular afferents. In control group, the number of colorectal afferents recorded per mouse were slightly lower in male mice than in female ones (38.7 vs. 45.2) with no significant difference in their distributions across thoracolumbar (TL) and lumbosacral (LS) DRG. In zymosan group, more afferents were recorded from each male mice than female ones (53.8 vs. 44.1) showing significantly higher TL innervation (T12, L1, and L2 DRG) in male group. Within the male groups, zymosan treatment resulted in a significant increase in the proportion of TL innervation as compared with saline treatment. In contrast, female mice showed no difference in the proportion of colorectal neurons between saline‐ and zymosan‐treated groups. Our results have revealed a significant sex difference in colorectal afferent innervation and sensitization in the context of behavioral visceral hypersensitivity. The current outcomes draw further focused research on the neurophysiological differences between sexes that could drive the differential gastrointestinal symptoms in male and female IBS patients.

Systematic Review of the Prevalence of Kidney Stones in Cystic Fibrosis.

Purpose: To investigate the prevalence of urolithiasis in cystic fibrosis (CF) and to summarize the available clinical features within this unique population. Methods: Studies reporting the prevalence of urolithiasis in CF patients were identified by a systematic search of the literature from inception to July 31, 2020 on three databases: Ovid Medline, Ovid Embase, and Web of Science. Data were extracted on a predetermined standardized form by two independent authors. Results: A total of 596 publications were retrieved and screened, 15 of which met the eligibility criteria. The publications were published between 1993 and 2019 and were all observational in design. There was a total of 2982 patients with CF included in this review. The overall prevalence of stone formation in the CF population was 4.6% (137/2982). The mean age of diagnosis was 25.1 ± 9.6 and ranged from 0.25 to 47. Ultrasound was the most common imaging modality for kidney stone diagnosis. There was no apparent sex difference, with a female to male ratio of 1:1. Surgical intervention was required in 37.8% (34/90) of cases. Stone recurrence was reported in 42.9% (33/77) of stone formers. Conclusions: This review provides the most recent update for the prevalence of urolithiasis in CF patients and summarizes the available clinical data. Our findings suggest that patients with CF could be at risk for developing stones at a younger age and require interventional management strategies at higher rates compared with the general population. Given the heterogeneity of the literature for urolithiasis in CF, larger population-based studies reporting the epidemiology, clinical features, and management strategies are required to further our understanding of urolithiasis in CF.

Comparative toxicokinetics of Trans-resveratrol and its major metabolites in Harlan Sprague Dawley rats and B6C3F1/N mice following oral and intravenous administration

Trans-resveratrol (RES) is a naturally occurring stilbene found in numerous plants and foods. Due to its widespread human exposure and lack of toxicity and carcinogenicity data, RES was nominated to the National Toxicology Program for testing. To aid the toxicology studies, the dose, sex, and species differences in RES toxicokinetics was investigated in Harlan Sprague Dawley rats and B6C3F1/N mice following single intravenous (IV) (10 mg/kg) or oral gavage administration (312.5, 625, and 1250 mg/kg and 625, 1250, and 2500 mg/kg in rats and mice, respectively).Following IV and gavage administration, systemic exposure of RES based on AUC was trans-resveratrol-3-O-β-D-glucuronide (R3G)> > trans-resveratrol-3-sulfate (R3S) > RES in both species. Following gavage administration Tmax_predicted values were ≤ 263 min for both species and sexes. RES elimination half-life was longer in rats than mice, and shortest in male mice. Clearance was slower in mice with no apparent sex difference in both species. In both rats and mice, following gavage administration AUC increased proportionally to the dose. After gavage administration, enterohepatic recirculation of RES was observed in both rats and mice with secondary peaks occurring around 640 min in the concentration-time profiles. RES was rapidly metabolized to R3S and R3G in both species. Extensive first pass conjugation and metabolism resulted in low levels of the parent compound RES which was confirmed by the low estimates for bioavailability. The bioavailability of RES was low, ~12–31% and ~2–6% for rats and mice, respectively, with no apparent difference between sexes.

Toxicokinetics of the plasticizer, N-butylbenzenesulfonamide, in plasma and brain following oral exposure in rodents: Route, species, and sex comparison

N-Butylbenzenesulfonamide (NBBS) is a widely used plasticizer and hence there is potential for human exposure via oral routes. This work investigates the toxicokinetic behavior of NBBS in rodents following a single gavage (20, 60, and 200 mg/kg body weight) or multi-day feed administration (500, 1000, and 2000 ppm). In male and female rats following gavage administration, maximum plasma NBBS concentration, Cmax, was reached at ≤0.539 h. Cmax increased proportionally to the dose. Area under the curve (AUC) increased more than proportionally to the dose and was 4- to 5-fold higher in females than in males. In mice, plasma Cmax was reached at ≤0.136 h and increased proportionally to the dose in female mice and more than proportionally to the dose in males. AUC increased more than proportionally to the dose with no apparent sex difference. Elimination of NBBS in plasma was faster in mice (half-life (h); mice ≤0.432, rat ≤3.55). Oral bioavailability was higher in female rats (≥60%) than males (23-52%) with apparent saturation of clearance at ∼200 mg/kg body weight in females. In mice, bioavailability (5-14%) was lower with no apparent sex difference. NBBS was detected in brains of rats and mice but with low brain:plasma ratios (rats, ≤5; mice, ≤1) suggesting low potential to cross the blood brain barrier. Systemic exposure in male rats and mice following a single gavage administration was ≥48-fold higher than multi-day feed exposure. These data demonstrate potential species, sex, dose- and route-related difference in toxicokinetics of NBBS in rodents.

Toxicokinetics and bioavailability of sulfolane, a ground water contaminant, following oral and intravenous administration in rodents: A dose, species, and sex comparison

Sulfolane is a ground water contaminant near refinery sites. The objective of this work was to investigate the toxicokinetics and bioavailability of sulfolane in male and female Harlan Hsd:Sprague Dawley® SD® rats and B6C3F1/N mice following a single oral administration of 10, 30, or 100 mg/kg. Sulfolane was rapidly absorbed in rats with the maximum plasma concentration, Cmax, reached at ≤1.47 h. Although Cmax increased proportionally to the dose, the half-life of elimination increased with the dose and the area under the concentration versus time curve (AUC) increased more than proportionally to the dose. In male and female rats, plasma elimination half-life increased with the dose from 1.97 to 6.33 h. Absorption of sulfolane in mice following oral administration was more rapid than in rats with Cmax reached at ≤0.55 h. In addition, mice had a shorter half-life (≤ 1.25 h) and a lower AUC than rats. In male and female mice, both Cmax and AUC increased more than proportionally to the dose. Bioavailability of sulfolane was higher in rats (81–83%) than mice (59–63%) at 10 mg/kg; at 30 and 100 mg/kg, bioavailability >100% in both species and sexes suggesting that the saturation of metabolism and clearance processes of sulfolane may begin at a single oral dose of ~30 mg/kg. There was no apparent sex difference in toxicokinetic parameters of sulfolane in rats and mice. These data demonstrate that sulfolane was well-absorbed following oral administration with high bioavailability in rats and mice with some species differences, but no sex difference.

Reciprocal interactions between prostaglandin E2- and estradiol-dependent signaling pathways in the injured zebra finch brain

BackgroundAstrocytic aromatization and consequent increases in estradiol are neuroprotective in the injured brain. In zebra finches, cyclooxygenase-activity is necessary for injury-induced aromatase expression, and increased central estradiol lowers neuroinflammation. The mechanisms underlying these influences are unknown. Here, we document injury-induced, cyclooxygenase-dependent increases in glial aromatase expression and replicate previous work in our lab showing increases in central prostaglandin E2 and estradiol following brain damage. Further, we describe injury-dependent changes in E-prostanoid and estrogen receptor expression and reveal the necessity of E-prostanoid and estrogen receptors in the injury-dependent, reciprocal interactions of neuroinflammatory and neurosteroidogenic pathways.MethodsAdult male and female birds were shams or received bilateral injections of the appropriate drug or vehicle into contralateral telencephalic lobes.ResultsInjuries sustained in the presence of indomethacin (a cyclooxygenase inhibitor) had fewer aromatase-expressing reactive astrocytes relative to injuries injected with vehicle suggesting that cyclooxygenase activity is necessary for the induction of glial aromatase around the site of damage. Injured hemispheres had higher prostaglandin E2 and estradiol content relative to shams. Importantly, injured hemispheres injected with E-prostanoid- or estrogen receptor-antagonists showed elevated prostaglandin E2 and estradiol, respectively, but lower prostaglandin E2 or estradiol-dependent downstream activity (protein kinase A or phosphoinositide-3-kinase mRNA) suggesting that receptor antagonism did not affect injury-induced prostaglandin E2 or estradiol, but inhibited the effects of these ligands. Antagonism of E-prostanoid receptors 3 or 4 prevented injury-induced increases in neural estradiol in males and females, respectively, albeit this apparent sex-difference needs to be tested more stringently. Further, estrogen receptor-α, but not estrogen receptor-β antagonism, exaggerated neural prostaglandin E2 levels relative to the contralateral lobe in both sexes.ConclusionThese data suggest injury-induced, sex-specific prostaglandin E2-dependent estradiol synthesis, and estrogen receptor-α dependent decreases in neuroinflammation in the vertebrate brain.

Rodent sex differences in disgust behaviors (anticipatory nausea) conditioned to a context associated with the effects of the toxin LiCl: Inhibition of conditioning following immune stimulation with lipopolysaccharide

This study examined sex differences in the establishment of lithium chloride (LiCl)-induced conditioned disgust behavior (anticipatory nausea) to a distinct context in adult male and female rats. Also examined were potential sex differences in response to treatment with the bacterial endotoxin, lipopolysaccharide (LPS), and its effect on learning and memory. Twenty-nine male and 31 female naïve Long-Evans rats were injected (intraperitoneally; i.p.) with either 200μg/kg LPS or 0.9% (NaCl), 90min prior to i.p. injections of either 128mg/kg LiCl or 0.9% NaCl, and immediately placed into a distinctive context for 30min (repeated over 4 conditioning days, spaced 72h apart). 72h following the final conditioning day, each subject was re-exposed to the context on a drug-free test day where orofacial and somatic behaviors were recorded. Results showed that LiCl-treated females conditioned stronger disgust reactions, relative to LiCl-treated males, as evidenced by significantly higher frequencies of conditioned “gaping” behavior (p<0.02) and forelimb flailing (p<0.01) in females. Pre-treatment with LPS during conditioning led to strong inhibition of conditioned disgust behavior, to levels that did not significantly differ from controls. Although there was no apparent sex difference in the degree of inhibition produced by LPS in this context-based rodent disgust model, males did exhibit significantly greater 24h body weight losses following LPS injections on the first two conditioning days, relative to females. The results of the current study provide strong evidence for a sex difference in the establishment of anticipatory nausea, as well as, evidence for a sex difference in the acute-phase response to endotoxin treatment.

Experience-Dependent Plasticity Drives Individual Differences in Pheromone-Sensing Neurons

Different individuals exhibit distinct behaviors, but studying the neuronal basis of individuality is a daunting challenge. Here, we considered this question in the vomeronasal organ, a pheromone-detecting epithelium containing hundreds of distinct neuronal types. Using light-sheet microscopy, we characterized in each animal the abundance of 17 physiologically defined types, altogether recording from half a million sensory neurons. Inter-animal differences were much larger than predicted by chance, and different physiological cell types showed distinct patterns of variability. One neuronal type was present in males and nearly absent in females. Surprisingly, this apparent sexual dimorphism was generated by plasticity, as exposure to female scents or single ligands led to both the elimination of this cell type and alterations in olfactory behavior. That an all-or-none apparent sex difference in neuronal types is controlled by experience-even in a sensory system devoted to "innate" behaviors-highlights the extraordinary role of "nurture" in neural individuality.

Reproductive Ecology and Human-Caused Mortality in the Japanese Mamushi Snake (Gloydius blomhoffii) on the Northernmost Main Island of Japan

Abstract Japanese Mamushi (Gloydius blomhoffii) has long been exploited for its medicinal value. We studied this snake's reproductive ecology on Hokkaido and assessed its vulnerability. We marked 299 individuals from 1999–2002 and kept 29 pregnant females in captivity until parturition. Pregnant females aggregated at gestation sites during summer and fall until just before parturition. Behavior suggestive of mating seasons was evident mostly in August and September. As expected, there was an apparent sex difference in body size in adults but not in neonates: females were larger than males. Consistent with previous reports, both neonates and adults were larger in Hokkaido than in southern Japan. The smallest pregnant female measured 44.8 cm in SVL, which was larger than values reported from southern regions. Offspring sex ratio was statistically equal: 88 males to 105 females. Litter size averaged 6.6 offspring. Longer females tended to produce larger litters and longer neonates. The proportion of pregnant...

Why men collect things? A case study of fossilised dinosaur eggs

Collecting entails substantial costs in terms of effort, money, time and space needed to find, obtain and store desirable items. Still, the non-utilitarian nature of collectibles suggests that a simple economic justification of this behaviour is unlikely. Moreover, the apparent sex difference, with collectors being almost exclusively men, indicates a possible reproductive motive. However, presently available theories have failed to identify these motives and predict its patterns leaving collecting behaviour unexplained. This paper employs recent developments in the fields of evolutionary psychology and theoretical biology in order to construct a plausible theory which accounts for collecting behaviour. In particular, it is argued that collecting has evolved to facilitate reliable communication between males with respect to their unobserved resource acquisition capacity. Based on this theoretical framework three hypotheses are derived: the desirability of a collectible item is positively related to its rarity, aesthetic pleasingness, and size. Evidence based on eBay auction sales of fossilised dinosaur eggs provides support for all three hypotheses.

Using the same bone density reference database for men and women provides a simpler estimation of fracture risk

Although low bone mineral density (BMD) predicts fractures, there are postulated sex differences in the fracture "threshold." Some studies demonstrate a higher mean BMD for men with fractures than for women, whereas others note similar absolute risk at the same level of BMD. Our objective was to test the preceding observations in the population-based Canadian Multicentre Osteoporosis Study (CaMOS). We included participants 50+ years of age at baseline. Mean BMD in men was higher than in women among both fracture cases and noncases. Three methods of BMD normalization were compared in age-adjusted Cox proportional hazards models. In a model using the same reference population mean and standard deviation (SD), there were strong effects of age and total-hip BMD for prediction of fractures but no significant effect of sex [hazard ratio (HR) = 0.97, 95% confidence interval (CI) 0.78-1.20] for men versus women. In a model using sex-specific reference means but a common SD, an apparent sex difference emerged (HR = 0.66, 95% CI 0.54-0.81) for men versus women. The sex term in the second model counterbalanced the higher risk introduced by the lower normalized BMD in men. A third model using sex-specific reference means and SDs gave nearly identical results. Parallel results for the three methods of normalization were seen when adjusting for clinical risk factors, excluding antiresorptive users and considering death as a competing risk. We conclude that no adjustment for sex is necessary when using common reference data for both men and women, whereas using sex-specific reference data requires a substantial secondary adjustment for sex.

Impact of an asthma education form on emergency relapse and admission for acute exacerbation of asthma

Study objectives: We determine the impact of an asthma education form on subsequent emergency department (ED) relapses and admissions for asthma during 6 months after ED discharge. Methods: We conducted a self-matched case-control study of adult patients aged 18 to 54 years presenting to the ED with acute exacerbation of asthma. Between September 1, 2003, and November 30, 2003, all discharged asthma patients received an education form with dosage and explanation of discharge medications, appointment information, and instructions to return to the ED using symptom-based and peak flow–based criteria. Control visits were ED visits for asthma exacerbation 1 year earlier (within 30 days of the index visit). ED relapses and admissions for asthma were then tabulated for the subsequent 6-month period. Results: Five hundred fifteen patients received a discharge education form, and, of these, 120 patients had a matched ED visit for an acute exacerbation of asthma in the previous year. There was a significant reduction in ED relapse at 6 months among patients receiving the education form: 79 ED relapses for the cases versus 91 for the controls (relative risk [RR] 0.87 95% confidence interval [CI] 0.76 to 0.997). Although there were fewer admissions among the cases (19 versus 24 [RR 0.79; 95% CI 0.50 to 1.25]), this was not statistically significant. When results were stratified by sex, women had significantly fewer ED relapses at 6 months: 48 for the cases versus 63 for the controls (relative risk [RR] 0.76; 95% 0.65 to 0.90). Men, however, showed no statistically significant reduction in ED relapse: 29 for the index versus 26 for the controls. Incidentally, the numbers for 2-week ED relapse and admission were too low to reach statistical significance. Conclusion: A simple education form given to adult patients on ED discharge for acute exacerbation of asthma may be effective in reducing ED relapse and admission during the subsequent 6 months. The apparent sex difference that we demonstrated deserves further study.

Preferential transmission of type 1 diabetes from parents to offspring: fact or artifact?

It has been widely reported that men with type 1 diabetes (T1D) tend to be more likely to transmit the disease to their offspring than their female counterparts in Caucasoid populations. Several theories to explain this preferential transmission have been proposed, but so far none of them has been unequivocally proven. Whatever the mechanism, confirmation or refutation of this observation is nonetheless important and practical to the design of future genetic studies of T1D. We carried out some statistical modeling of the preferential transmission. The well-established fact that males have higher a prevalence of T1D than females, an apparent sex difference in fecundity, and a possible misclassification of gestational diabetes mellitus (GDM) as T1D in women have been considered. We demonstrated, first, that the ascertainment of study families through the affected offspring with T1D would generate a higher proportion of fathers than mothers having T1D, even though there was no preferential transmission at all. This can be explained by the male preponderance in T1D prevalence as compared with females, coupled with a greater likelihood of being selected and/or recruited for study in families with T1D fathers due to the fecundity difference. Second, when the study population is ascertained through affected parents, misclassification of mothers with GDM as T1D, and the existence of male/female difference in fecundity in conjunction with a birth order effect, can contribute to the observed preferential transmission, even though there was none. In light of the plausibility of assumptions employed in the analysis and, in particular, an apparent failure to critically examine the effects of these causes of bias in earlier studies, it is perhaps prudent to say that the jury for the existence of preferential transmission in T1D is still out.