Understanding desiccation tolerance and sex-specific responses in Bryum argenteum: insights from phenological phases and physiological analyses.

BACKGROUND AND AIMS: Desiccation tolerance (DT) is crucial for survival in arid environments, where organisms develop strategies in reproduction, maintenance and defence to cope with water scarcity. Therefore, investigating the relationship between reproduction and DT is essential to understand the ecology and adaptive strategies of species. This study explores the connection between the development of male and female gametangia in the moss Bryum argenteum and the decrease in DT during the progression of phenological phases in gametangia and protonema. METHODS: Samples collected from a dry tropical forest in Brazil were cultivated, cloned and subjected to desiccation. Subsequently, the physiological parameters of shoots and protonemata were analysed. Shoot and protonema regeneration were monitored for 28 d after the physiological analyses. Both phases were subjected to control and desiccation treatments. KEY RESULTS: Significant effects of desiccation and sex on the physiological parameters and regeneration capacity of shoots and protonemata were found. Male shoots generally exhibited lower values of Fv/Fm (quantum efficiency of photosystem II) and ϕPSII (effective quantum yield of photosystem II), while females demonstrated higher values and better recovery after desiccation. Protonemata also showed variation in Fv/Fm over time and with sex, with no significant differences in ϕPSII between them. Desiccated male shoots had higher mortality rates and produced fewer new shoots. For females, the regeneration patterns varied between the desiccation-exposed groups and the control, with decreased shoot production, and some protonemata growing into filaments without forming shoots. CONCLUSION: These findings improve our understanding of the ecological responses of bryophytes to desiccation stress and provide insights into their adaptive strategies in challenging environments, such as the possible rarity of males in dioicous moss populations.

Sex-specific difference in phenotype of Kabuki syndrome type 2 patients: a matched case-control study.

BACKGROUND: Kabuki syndrome (KS) is a monogenic disorder leading to special facial features, mental retardation, and multiple system malformations. Lysine demethylase 6A, (KDM6A, MIM*300128) is the pathogenic gene of Kabuki syndrome type 2 (KS2, MIM#300867), which accounts for only 5%-8% of KS. Previous studies suggested that female patients with KS2 may have a milder phenotype. METHOD: We summarized the phenotype and genotype of KS2 patients who were diagnosed in Shanghai Children's Medical Center since July 2017 and conducted a 1:3 matched case-control study according to age and sex to investigate sex-specific differences between patients with and without KS2. RESULTS: There were 12 KS2 cases in this study, and 8 of them matched with 24 controls. The intelligence quotient (IQ) score of the case group was significantly lower than that of the control group (P < 0.001). In addition, both the incidence of intellectual disability (ID) (IQ < 70) and moderate-to-severe ID (IQ < 55) were significantly higher in the case group than those in the control group. No sex-specific difference was found in the incidence of ID or moderate-to-severe ID between the female cases and female controls, whereas there was a significant difference between male cases and male controls. Furthermore, the rate of moderate-to-severe ID and congenital heart disease (CHD) was significantly higher in the male group than that in the female group. CONCLUSIONS: Our results showed that a sex-specific difference was exhibited in the clinical phenotypes of KS2 patients. The incidence of CHD was higher in male patients, and mental retardation was significantly impaired. However, the female patients' phenotype was mild.

Sex representation in neurodegenerative and psychiatric disorders' preclinical and clinical studies.

Many studies show the importance of biological sex for the onset, progression, and response to treatment in brain disorders. In line with these reports, health agencies have requested that all trials, both at the clinical and preclinical level, use a similar number of male and female subjects to correctly interpret the results. Despite these guidelines, many studies still tend to be unbalanced in the use of male and female subjects. In this review we consider three neurodegenerative disorders: Alzheimer's disease, Parkinson's disease, Amyotrophic lateral sclerosis, and three psychiatric disorders: Depression, Attention Deficit Hyperactivity Disorder, and Schizophrenia. These disorders were chosen because of their prevalence and their recognized sex-specific differences in onset, progression, and response to treatment. Alzheimer's disease and Depression demonstrate higher prevalence in females, whereas Parkinson's Disease, Amyotrophic lateral sclerosis, Attention Deficit Hyperactivity Disorder, and schizophrenia show higher prevalence in males. Results from preclinical and clinical studies examining each of these disorders revealed sex-specific differences in risk factors, diagnostic biomarkers, and treatment response and efficacy, suggesting a role for sex-specific therapies in neurodegenerative and neuropsychiatric disorders. However, the qualitative analysis of the percentage of males and females enrolled in clinical trials in the last two decades shows that for most of the disorders, there is still a sex bias in the patients' enrolment.

Sex and Estrous Cycle Are Not Mediators of S-Ketamine's Rapid-Antidepressant Behavioral Effects in a Genetic Rat Model of Depression.

BACKGROUND: Recent preclinical and clinical studies have shed light on the possible impact of sex and estrous/menstrual cycle on ketamine's antidepressant action but with incongruous results. The preclinical studies that have shown the effects of ovarian sex hormones have not done so in animal models of depression. Thus, the aim of the present study is to scrutinize the acute behavioral responses to a subanesthetic dose of S-ketamine in males vs females and in different estrous phases in free-cycling females in a well-powered translational approach. METHODS: We evaluated the behavioral sensitivity to 20 mg/kg S-ketamine (i.p.) in male and female Flinders Sensitive Line rats (FSLs) and their counterpart Flinders Resistant Line rats (FRLs) subjected to the open field and forced swim tests. Female rats were disaggregated into different estrous phases, and the behavioral outcomes were compared. RESULTS: Acute administration of S-ketamine had robust antidepressant-like effects in FSLs. Within our study power, we could not detect sex- or estrous cycle-specific different antidepressant-like responses to S-ketamine in FSLs. Fluctuations in the levels of ovarian sex hormones across different estrous cycles did not behaviorally affect S-ketamine's rapid-acting antidepressant mode of action. No sex-related or estrous cycle-related impact on behavioral despair was observed even among FRLs and saline-treated FSLs. CONCLUSIONS: We conclude that physiological oscillations of estrogen and progesterone levels neither amplify nor diminish the behavioral antidepressant-like effect of S-ketamine. In addition, fluctuations of ovarian sex hormones do not predispose female animals to exhibit enhanced or reduced depressive-like and anxiety-like behaviors.

Neonatal Exposure to Valproate Induces Long-Term Alterations in Steroid Hormone Levels in the Brain Cortex of Prepubertal Rats.

Valproic acid (VPA) is a known drug for treating epilepsy and mood disorders; however, it is not recommended for pregnant women because of its possible teratogenicity. VPA affects neurotransmission and gene expression through epigenetic mechanisms by acting as a histone deacetylase inhibitor and has been used to establish animal models of autism spectrum disorder (ASD). However, studies on the long-term effects of early exposure to VPA on glucocorticoid and neurosteroid synthesis in the brain are lacking. Therefore, this study aimed to investigate the long-term changes in metabolic alterations and gene expression regulation according to sex, using metabolic steroid profiling data from cerebral cortex samples of rats four weeks after VPA exposure (400 mg/kg). In neonatal VPA-exposed models, estradiol levels decreased, and cytochrome P450 19A1 gene (Cyp19a1) expression was reduced in the prepubertal male cortex. Progesterone and allopregnanolone levels decreased, and 3ß-hydroxysteroid dehydrogenase 1 gene (Hsd3b1) expression was also downregulated in the prepubertal female cortex. Furthermore, cortisol levels increased, and mRNA expression of the nuclear receptor subfamily 3 group C member 1 gene (Nr3c1) was downregulated in the cortices of both sexes. Unlike the neonatal VPA-exposed models, although a decrease in progestin and estradiol levels was observed in females and males, respectively, no differences were observed in cortisol levels in the cortex tissues of 8-week-old adult rats administered VPA for four weeks. These results indicate that early environmental chemical exposure induces long-term neurosteroid metabolic effects in the brain, with differences according to sex.

A more than four-fold sex-specific difference of autism spectrum disorders and the possible contribution of pesticide usage in China 1990-2030.

Autism spectrum disorders (ASDs) are prevalent in children and adolescents and disproportionately affect males, and the main contributing factors underlying male vulnerability remain widely unknown. Pesticide use is widely reported to be associated with ASD risk, and the cases of pesticide poisoning incidence in rural areas are remarkably higher than those in the urban areas while the prevalence of ASDs in rural areas was higher than that in urban areas and the rate of male pesticide poisoning was significantly higher than female. Thus, pesticide usage may be an important contributing factor for causing sex-specific differences of ASD incidence. ASD burden was analyzed by using the data of ASD number, ASD rate (ASD cases per 100,000 persons) and disability-adjusted life years (DALYs) from 1990 to 2019. The changes from 1990 to 2030 were predicted using autoregressive integrated moving average (ARIMA) in time series forecasting based on the small values of Akaike information criterion and Bayesian information criterion. Finally, the relationship between ASD rate and pesticide usage risk index (PURI) was analyzed via Pearson's correlation coefficient. ASD number, ASD rate and DALYs will be reduced by 45.5% ± 8.2% (t = 9.100 and p = 0.0119), 56.6% ± 10.2% (t = 9.111 and p = 0.0118), and 44.9% ± 7.0% (t = 20.90 and p = 0.0023) from 1990 to 2030 in China. PURI has a strong relationship with ASD rate (rho = 0.953 to 0.988 and p < 0.0001). Pesticide poisoning incidence in males is up to 2-fold higher than that in females. ASD number and DALYs in males are 4-fold higher than those in females. Furthermore, there is growing evidence supporting that males are more susceptible than females to pesticides with sex differences in neurotoxicogenetics. Therefore, pesticide poisoning may be a contributing factor for causing the sex differences of ASD. Much work still needs to be done to confirm that.

Sex-Specific Effect of Obesity on Epiblepharon in Different Age Groups: A Case-Control Study.

Obesity has been regarded as a risk factor for several ocular diseases. This study aims to investigate the age- and sex-specific relationship between epiblepharon and obesity in children. A retrospective case-control study was conducted using the Chang Gung Research Database. Children ≤ 18 years of age with epiblepharon were identified from 1 January 2009 to 31 December 2019. Children were classified into three groups: normal, overweight and obese groups. A total of 513 patients and 1026 controls (57.7% males) aged 1 to 18 matched by sex and age were included in the analysis. The median body mass index (BMI) of children with epiblepharon was significantly higher than that of children without epiblepharon (p < 0.001). In the subgroup analysis, among boys aged 4 to 9 years, the BMI in boys with epiblepharon was significantly higher than that in boys without epiblepharon (p < 0.05) and the risk of epiblepahron in overweight/obese boys was significantly higher than in non-overweight boys (OR = 1.74, 95% CI = 1.07-2.82 for age 4 to 6; OR = 3.06, 95% CI = 1.56-6.03 for age 7 to 9). On the other hand, among girls aged 13 to 18 years, the BMI in adolescent girls with epiblepharon was significantly higher than that in the control group (p < 0.05) and overweight/obese girls had a statistically higher risk of persistent epiblepharon than non-overweight girls (OR = 3.70, 95% CI = 1.38-9.97). The association between obesity and epiblepharon varies in strength according to age in a sex-specific manner.

Corrigendum: Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

[This corrects the article DOI: 10.3389/fendo.2021.695614.].

Sex-Specific Differences in the Effect of Free Testosterone on Sarcopenia Components in Older Adults.

Objective: The association of free testosterone (FT) with sarcopenia and its components is well known in men but incompletely understood in women. We examined the association of baseline FT with the prevalence and incidence of sarcopenia and its components in community-dwelling older adults. Design: Cross-sectional and longitudinal analysis from the prospective population-based Korean Frailty and Aging Cohort Study. Methods: A total of 1,879 community-dwelling older adults aged 70-84 years were enrolled for cross-sectional analysis and 1,583 subjects who participated in the 2-year follow-up survey were included for longitudinal analysis. Baseline FT levels was measured by radioimmunoassay. Skeletal muscle mass, handgrip strength, and physical performance tests were measured at baseline and after 2-year follow-up. Sarcopenia was defined by the diagnostic criteria of the Asian Working Group for Sarcopenia (AWGS). Results: Continuous FT levels was positively associated with the prevalence of sarcopenia in men (odds ratio [OR]=0.95; 95% confidence interval [CI]=0.89-1.00)] and women (OR=0.64, 95% CI=0.42-0.99) after adjusting for multiple confounders. In prospective analysis, low FT levels was associated with a decrease in handgrip strength in women (ß=-0.61; p=0.010) and a reduction in Timed "Up and Go" (TUG) test (ß=0.53; p=0.008) in men after 2 years. No significant correlations were found between FT levels and the incidence of sarcopenia. Conclusions: Low levels of FT may be a significant determinant of decreases in muscle strength in women and declines in physical performance in men after 2 years. Low FT do not predict loss of muscle mass in both men and women.

Pollutant-sex specific differences in respiratory hospitalization and mortality risk attributable to short-term exposure to ambient air pollution.

BACKGROUND: Many studies have reported associations of individual pollutants with respiratory hospitalization and mortality based on different populations, which makes it difficult to directly compare adverse health effects among multiple air pollutants. OBJECTIVES: The study goal is to compare acute respiratory-related hospitalization and mortality associated with short-term exposure to three ambient air pollutants and analyze differences in health risks by season, age and sex. METHODS: Hourly measurements of air pollutants (ozone, NO2, PM2.5) and temperature were collected from ground-monitors for 24 cities along with daily hospitalization (1996-2012) and mortality (1984-2012) data. National associations between air pollutant and health outcome were estimated for season (warm, cold vs. year-round), age (base ≥ 1, seniors > 65), and sex (females ≥ 1 and males ≥ 1) using Bayesian hierarchical models. RESULTS: Overall, the three air pollutants were significantly associated with acute respiratory health outcomes at different lag-days. For respiratory hospitalization, the increased risks in percent changes with 95% posterior intervals for a 10-unit increase in each pollutant were: ozone (lag1, 0.7% (0.4, 0.9)), NO2 (lag0, 0.7% (0.1, 1.4)), and PM2.5 (lag1, 1.3% (0.7, 1.9)). For respiratory mortality: ozone (lag2, 1.2% (0.4, 1.9)), NO2 (lag1, 2.1% (0.6, 3.5)), and PM2.5 (lag1, 0.6% (-1.0, 2.2)). While some differences in risk were observed by season and age group, sex-specific differences were more pronounced. Compared with males, females had a higher respiratory mortality risk (1.8% (0.6, 2.9) vs 0.5% (-0.3, 1.3)) from ozone, a higher respiratory hospitalization risk (0.9% (0.0, 1.8) vs 0.6% (-0.3, 1.4)) but lower mortality risk (1.4% (-1.0, 3.7) vs 2.2% (0.4, 4.0)) from NO2, and a lower hospitalization risk (0.7% (-0.2, 1.7) vs 1.8% (1.0, 2.6)) from PM2.5. CONCLUSION: This study reports significant health effects of short-term exposure to three ambient air pollutants on respiratory hospitalization (ozone≈NO2 < PM2.5 per-10 unit; ozone>NO2 ≈ PM2.5 per-IQR) and mortality (ozone≈NO2 > PM2.5) in Canada. Pollutant-sex-specific differences were found, but inconclusive due to limited biological and physiological explanations. Further studies are warranted to understand the pollutant-sex specific differences.

Comparison of hospitalization and mortality associated with short-term exposure to ambient ozone and PM2.5 in Canada.

BACKGROUND: Hospitalization and mortality (H-M) have been linked to air pollution separately. However, previous studies have not adequately compared whether air pollution is a stronger risk factor for hospitalization or mortality. This study aimed to investigate differences in H-M risk from short-term ozone and PM2.5 exposures, and determine whether differences are modified by season, age, and sex. METHODS: Daily ozone, PM2.5, temperature, and all-cause H-M counts (ICD-10, A00-R99) were collected for 22-24 Canadian cities for up to 29 years. Generalized additive Poisson models were employed to estimate associations between each pollutant and health outcome, which were compared across season (warm, cold, or year-round), age (all ages or seniors > 65), and sex. RESULTS: Overall, ozone and PM2.5 showed higher season-specific risk of mortality than hospitalization: warm-season ozone: 0.54% (95% credible interval, 0.20, 0.85) vs. 0.14% (0.02, 0.27) per 10 ppb; and year-round PM2.5: 0.90% (0.33, 1.41) vs. 0.29% (0.03, 0.56) per 10 µg/m3. While age showed little H-M difference, sex appeared to be a modifier of H-M risk. While females had higher mortality risk, males had higher hospitalization risk: for females, ozone 0.87% (0.36, 1.35) vs. -0.03% (-0.18, 0.11) and PM2.5 1.19% (0.40, 1.90) vs. 0.19% (-0.10, 0.47); and for males ozone 0.20% (-0.28, 0.65) vs. 0.35% (0.18, 0.51). CONCLUSION: This study found H-M differences attributable to ozone and PM2.5, suggesting that both are stronger risk factors for mortality than hospitalization. In addition, there were clear H-M differences by sex: specifically, females showed higher mortality risk and males showed higher hospitalization risk.

Potassium intake, skeletal muscle mass, and effect modification by sex: data from the 2008-2011 KNHANES.

BACKGROUND: A loss of muscle mass may be influenced by multiple factors. Insulin sensitivity and metabolic acidosis are associated with muscle wasting and may be improved with potassium intake. This study evaluated the association between dietary potassium intake and skeletal muscle mass. METHODS: We performed a cross-sectional study with data obtained from the Korean National Health and Nutrition Examination Survey (KNHANES) (2008-2011). Participant's daily food intake was assessed using a 24-h recall method. Appendicular skeletal muscle mass (ASM) was calculated as the sum of muscle mass in both arms and legs, measured using dual energy X-ray absorptiometry. The skeletal muscle index (SMI) was calculated as ASM divided by height2 (kg/m2). Low muscle mass was defined as a SMI < 7.0 kg/m2 for men and < 5.4 kg/m2 for women. RESULTS: Data from 16,558 participants (age ≥ 19 years) were analyzed. Participants were categorized into quintiles according to their potassium intake. Sex-specific differences were found in the association between potassium intake and muscle mass (PInteraction < 0.001). In men, higher potassium intake was associated with lower odds for low muscle mass; the fully adjusted odds ratios (95% confidence intervals) were 0.78 (0.60-1.03), 0.71 (0.54-0.93), 0.68 (0.51-0.90), and 0.71 (0.51-0.98) for the top four quintiles (referenced against the lowest quintile), respectively. However, this association was attenuated in women after adjusting for total energy intake. Higher potassium intakes were also associated with a greater SMI. CONCLUSIONS: Higher dietary potassium intake decreased the odds of low muscle mass in men but not in women.

Dipeptidyl peptidase 3 modulates the renin-angiotensin system in mice.

Dipeptidyl peptidase 3 (DPP3) is a zinc-dependent hydrolase involved in degrading oligopeptides with 4-12 amino acid residues. It has been associated with several pathophysiological processes, including blood pressure regulation, pain signaling, and cancer cell defense against oxidative stress. However, the physiological substrates and the cellular pathways that are potentially targeted by DPP3 to mediate these effects remain unknown. Here, we show that global DPP3 deficiency in mice (DPP3-/-) affects the renin-angiotensin system (RAS). LC-MS-based profiling of circulating angiotensin peptides revealed elevated levels of angiotensin II, III, IV, and 1-5 in DPP3-/- mice, whereas blood pressure, renin activity, and aldosterone levels remained unchanged. Activity assays using the purified enzyme confirmed that angiotensin peptides are substrates for DPP3. Aberrant angiotensin signaling was associated with substantially higher water intake and increased renal reactive oxygen species formation in the kidneys of DPP3-/- mice. The metabolic changes and altered angiotensin levels observed in male DPP3-/- mice were either absent or attenuated in female DPP3-/- mice, indicating sex-specific differences. Taken together, our observations suggest that DPP3 regulates the RAS pathway and water homeostasis by degrading circulating angiotensin peptides.

Temporal trends in associations between ozone and circulatory mortality in age and sex in Canada during 1984-2012.

BACKGROUND: Considerable research has been conducted on the association between ground-level ozone (ozone) and various causes of mortality, but the relationships by age and sex (biological) have been inconsistent, and temporal trends remain unexplored. OBJECTIVES: The study goals are to investigate the adverse health effects of short-term exposure to ozone on circulatory mortality by age and sex, and to examine trends in annual health effects. METHODS: Daily ozone, temperature, and circulatory mortality counts (ICD I00-I99) were collected for 24 urban cities for 29 years (1984-2012). Associations between ozone and circulatory mortality were estimated using generalized additive Poisson models for season (warm vs. cold), age [base (≥1) vs. seniors (>65)], and sex, accounting for confounders (calendar-time, temperature, day of the week). City-specific estimates were pooled to represent national associations through Bayesian hierarchical models. RESULTS: While the cold season returned insignificant estimates, the warm season showed statistically significant associations: a 10 ppb increase in ozone was associated with 0.7% increase in circulatory mortality with a 95% posterior interval of 0.2%, 1.1%. One-day lagged ozone in the warm season showed little age differences [0.7% (0.23%, 1.12%) vs. 0.8% (0.22%, 1.27%)], but visible sex differences: females were at a higher circulatory mortality risk than males [1.1% (0.31%, 1.71%) vs. 0.3% (-0.46%, 0.98%)]. Annual estimates suggest overall up-down temporal changes; a slightly increasing trend until 2002-2004, and a generally decreasing trend thereafter. CONCLUSION: This study found noticeable sex-related differences in circulatory mortality attributable to short-term exposure to ozone. Further research is warranted to understand whether sex alone, or unknown interactions with other factors derived the differences, and to clarify the specific biological mechanisms underlying differences in risk estimates between females and males.

Sex-Specific Differences in Cognitive Abilities Associated with Childhood Cadmium and Manganese Exposures in School-Age Children: a Prospective Cohort Study.

To examine sex-specific associations of neonatal and childhood exposure to eight trace elements with cognitive abilities of school-age children. The association between exposure and effects was assessed among 296 school-age children from a population-based birth cohort study, who had manganese (Mn), cadmium (Cd), and lead (Pb) exposure measured in cord blood and chromium (Cr), manganese, cobalt (Co), copper (Cu), arsenic (As), selenium (Se), cadmium, and lead exposure quantified in spot urine. Cognitive abilities were assessed using the Wechsler Intelligence Scale for Children-Chinese Revised (WISC-CR). Generalized linear models were performed to analyze associations of intelligence quotient (IQ) with trace element concentrations in cord blood and urinary trace element levels. General linear models were used to evaluate association between exposure fluctuation and children's IQ. Urinary Cd concentrations were negatively associated with full-scale IQ (ß = - 3.469, 95% confidence interval (CI) - 6.291, - 0.647; p = 0.016) and performance IQ (ß = - 4.012, 95% CI - 7.088, - 0.936; p = 0.011) in girls; however, neonatal Cd exposure expressed as Cd concentrations in cord blood was in inverse associations with verbal IQ (ß = - 2.590, 95% CI - 4.570, - 0.609; p = 0.010) only in boys. Positive association between urinary Mn concentrations and performance IQ (ß = 1.305, 95% CI 0.035, 2.575; p = 0.044) of children was observed, especially in girls. In addition, inverse association of urinary Cu concentrations with verbal IQ (ß = - 2.200, 95% CI - 4.360, - 0.039; p = 0.046) was only found in boys. Childhood Cd exposure may adversely affect cognitive abilities, while Mn exposure may beneficially modify cognitive abilities of school-age children, particularly in girls.

Revealing sex-specific molecular changes in hypoxia-ischemia induced neural damage and subsequent recovery using zebrafish model.

Functional recovery from hypoxia-ischemia depends on an individual's response to the ischemic damage and recovery. Many of the neurological disorders, including cerebral stroke have sex-specific characteristics. Deciphering the differential molecular mechanisms of sex-specific recovery from hypoxic-ischemic insult can improve medical practice in the treatment of cerebral stroke. In the present study, we describe the establishment of a sex-specific global hypoxia-ischemia neural damage and repair model in zebrafish. During hypoxic exposure a delayed behavioural response was observed in female fish that resumed normal swimming pattern earlier than their male counterparts. Moreover, female appeared more affected as they showed restricted locomotor and exploratory behaviour in novel tank test, reduced mitochondrial enzyme activity, enhanced DNA damage, and cell death after hypoxia insult. However, they showed a faster recovery as compared to male. Analysis of mRNA and protein expression levels of some characteristic hypoxic-ischemic markers showed notable sex-specific differences. Using zebrafish model, we have uncovered cellular and molecular differences in sex-specific systemic responses during the post-hypoxia recovery. This insight might help in devising better therapeutic strategy for stroke in female patients.

Sex-Specific Differences in HLA Antibodies after Pneumococcal Vaccination in Kidney Transplant Recipients.

In transplant recipients vaccination against Streptococcus pneumoniae is recommended to reduce mortality from invasive pneumococcal disease. It is still debated if vaccination in transplant recipients triggers alloresponses. Therefore, it was our aim to define if vaccination with Prevenar 13®, a 13-valent, conjugated pneumococcal vaccine (Pfizer, New York, NY, USA) that acts T cell dependently, induces human leukocyte antigen (HLA) antibodies in clinically stable kidney transplant recipients. Forty-seven patients were vaccinated once with Prevenar 13® and HLA antibodies were determined prior to vaccination and at month 1 and 12 thereafter. In parallel, pneumococcal IgG antibodies were measured. Using Luminex™ Mixed Beads technology (One Lambda/Thermo Fisher, Canoga Park, CA, USA) we observed overall no change in HLA antibodies after vaccination. Pneumococcal antibodies increased significantly at month 1 (p < 0.0001) and remained elevated at month 12 (p < 0.005). A more detailed analysis of HLA antibodies showed that in 18 females HLA class I and II antibodies increased significantly at month 1 and 12 (p < 0.05); whereas in 29 males HLA class I and II antibodies tended to decrease. Using Luminex™ Single Antigen Beads assay, no de novo donor-specific HLA antibodies were detected after vaccination. In conclusion, the current data indicate that females may be more susceptible to the induction of (non-specific) HLA antibodies after vaccination.

Sex-specific difference in age distribution of congenital lower eyelid epiblepharon in a Japanese population.

PURPOSE: To examine the sex-specific differences in age distribution of Japanese patients with congenital lower eyelid epiblepharon. STUDY DESIGN: A retrospective, observational study. METHODS: A total of 291 patients (87 men, 204 women) who underwent modified Hotz for correction of congenital lower eyelid epiblepharon were included in this study. Data on sex, age at surgical intervention, and affected side were collected. Patients' age was classified according to the orbital growth pattern (0-3 years, 4-6 years, 7-12 years, 13-15 years, and ≥ 16 years). The sex-specific difference in age distribution was analysed using Pearson's chi-squared test. RESULTS: Among male patients, 75 (86.2%) underwent surgery during 4-12 years of age. Only 2 (2.3%) boys had surgery at 13-15 years and 1 had it while he was ≥ 16 years. Among female patients, 11 (5.4%) underwent surgery at 13-15 years and 59 (28.9%) at ≥ 16 years. The age distribution was significantly different between sexes (P < 0.001). CONCLUSION: Among patients aged ≥13 years, there were more women compared to men. This implies that congenital lower eyelid epiblepharon is more persistent in females and may reflect slower and less orbital growth from 13 years of age and onwards in females. The results suggest that as long as there are no severe corneal complications and no risk for amblyopia, conservative management may be a good option for males since spontaneous resolution is likely to occur. However, for females aged 13 years or more, the threshold for surgical intervention should be lower.

Toll family members bind multiple Spätzle proteins and activate antimicrobial peptide gene expression in Drosophila.

The Toll signaling pathway in Drosophila melanogaster regulates several immune-related functions, including the expression of antimicrobial peptide (AMP) genes. The canonical Toll receptor (Toll-1) is activated by the cytokine Spätzle (Spz-1), but Drosophila encodes eight other Toll genes and five other Spz genes whose interactions with one another and associated functions are less well-understood. Here, we conducted in vitro assays in the Drosophila S2 cell line with the Toll/interleukin-1 receptor (TIR) homology domains of each Toll family member to determine whether they can activate a known target of Toll-1, the promoter of the antifungal peptide gene drosomycin. All TIR family members activated the drosomycin promoter, with Toll-1 and Toll-7 TIRs producing the highest activation. We found that the Toll-1 and Toll-7 ectodomains bind Spz-1, -2, and -5, and also vesicular stomatitis virus (VSV) virions, and that Spz-1, -2, -5, and VSV all activated the promoters of drosomycin and several other AMP genes in S2 cells expressing full-length Toll-1 or Toll-7. In vivo experiments indicated that Toll-1 and Toll-7 mutants could be systemically infected with two bacterial species (Enterococcus faecalis and Pseudomonas aeruginosa), the opportunistic fungal pathogen Candida albicans, and VSV with different survival times in adult females and males compared with WT fly survival. Our results suggest that all Toll family members can activate several AMP genes. Our results further indicate that Toll-1 and Toll-7 bind multiple Spz proteins and also VSV, but they differentially affect adult survival after systemic infection, potentially because of sex-specific differences in Toll-1 and Toll-7 expression.

Behavioural Phenotypic Plasticity of Submerged Oviposition in Damselflies (Insecta: Odonata).

Emerald damselfly Lestes sponsa is a common species within the temperate zone, with no special need for protection. The tactic of submerged oviposition is well known from other Odonata species, but has rarely been noticed or described in Lestes sponsa. Our study investigated the tactics of oviposition in this species, and shows that submerged oviposition indeed occurs frequently in Lestes sponsa. We experimentally tested the difference in the roles of males and females during the submerged ovipositional behaviour by combining males/females from submerging populations with males/females from non-submerging populations. We discovered that, whereas submerging males coupling with non-submerging females did not lead to submersion, the opposite combination of pairs submerged. Other patterns of submersions are discussed further in this paper. Our research led to the conclusion that damselflies have the ability to learn and react to different situations in keeping with the learning potential of insects in general.