Evaluating gender effect in the generic bioequivalence studies by physiologically based pharmacokinetic modeling - A case study of dextromethorphan modified release tablets.

The United States Food and Drug Administration guidelines for the bioequivalence (BE) testing of the generic drug products suggests that there should be an equal proportion of male and female population in the BE study. Despite this requirement, many generic drug companies do not maintain the suggested proportion of female population in their studies. Several socio-economic and cultural factors lead to lower participation of the females in the BE studies. More recently, the regulatory agencies across the globe are requesting the generic drug companies to demonstrate the performance of their drug products in the under-represented sex via additional studies. In this work, we describe the case of Dextromethorphan modified release tablets where the gender effect on the product performance was evaluated by physiologically based pharmacokinetic (PBPK) modeling approach. We have compared the drug product's performance by population simulations considering four different scenarios. The data from all-male population (from in house Pharmacokinetic [PK] BE studies) was considered as a reference and other scenarios were compared against the all-male population data. In the first scenario, we made a comparison between all-male (100% male) vs all-female (100% female) population. Second scenario was as per agency's requirements-equal proportion of male and female in the BE study. As an extreme scenario, 100% male vs 30:70 male:female was considered (higher females than males in the BE studies). Finally, as a more realistic scenario, 100% male versus 70:30 male:female was considered (lower females than males in the BE studies). Population PK followed by virtual BE was employed to demonstrate the similarity/differences in the drug product performance between the sexes. This approach can be potentially utilized to seek BE study waivers thus saving cost and accelerating the entry of the generic products to the market.

Arithmetic problem size modulates brain activations in females but not in males.

Numerous empirical studies have reported that males and females perform equally well in mathematical achievement. However, still to date, very limited is understood about the brain response profiles that are particularly characteristic of males and females when solving mathematical problems. The present study aimed to tackle this issue by manipulating arithmetic problem size to investigate functional significance using functional magnetic resonance imaging (fMRI) in young adults. Participants were instructed to complete two runs of simple calculation tasks with either large or small problem sizes. Behavioural results suggested that the performance did not differ between females and males. Neuroimaging data revealed that sex/gender-related patterns of problem size effect were found in the brain regions that are conventionally associated with arithmetic, including the left middle frontal gyrus (MFG), left intraparietal sulcus (IPS) and insula. Specifically, females demonstrated substantial brain responses of problem size effect in these regions, whereas males showed marginal effects. Moreover, the machine learning method implemented over the brain signal levels within these regions demonstrated that sex/gender is discriminable. These results showed sex/gender effects in the activating patterns varying as a function of the distinct math problem size, even in a simple calculation task. Accordingly, our findings suggested that females and males use two complementary brain resources to achieve equally successful performance levels and highlight the pivotal role of neuroimaging facilities in uncovering neural mechanisms that may not be behaviourally salient.

Age, gender and body-mass-index relationships with in vivo CB1 receptor availability in healthy humans measured with [11C]OMAR PET.

Brain cannabinoid 1 receptors (CB1Rs) contribute importantly to the regulation of autonomic tone, appetite, mood and cognition. Inconsistent results have been reported from positron emission tomography (PET) studies using different radioligands to examine relationships between age, gender and body mass index (BMI) and CB1R availability in healthy individuals. In this study, we examined these variables in 58 healthy individuals (age range: 18-55 years; 44 male; BMI=27.01±5.56), the largest cohort of subjects studied to date using the CB1R PET ligand [11C]OMAR. There was a significant decline in CB1R availability (VT) with age in the pallidum, cerebellum and posterior cingulate. Adjusting for BMI, age-related decline in VT remained significant in the posterior cingulate among males, and in the cerebellum among women. CB1R availability was higher in women compared to men in the thalamus, pallidum and posterior cingulate. Adjusting for age, CB1R availability negatively correlated with BMI in women but not men. These findings differ from those reported using [11C]OMAR and other radioligands such as [18F]FMPEP-d2 and [18F]MK-9470. Although reasons for these seemingly divergent findings are unclear, the choice of PET radioligand and range of BMI in the current dataset may contribute to the observed differences. This study highlights the need for cross-validation studies using both [11C]OMAR and [18F]FMPEP-d2 within the same cohort of subjects.

Gender differences in screening self-reported psychotic symptoms in a first help-seeking population.

Gender differences in the frequency and severity of psychotic symptoms have been widely reported. However, in the screening process for the detection of early psychosis, gender differences were largely overlooked in China. This study investigated gender differences in self-reported psychotic symptoms in a clinical population who initially visited a mental health service. In total, 1931 consecutive new patients were included in the current analysis, with a mean age of 25.3 years, including 852 (44.1%) men and 1079 (55.9%) women, of whom 388 (20.1%) had psychotic disorders and 1543 (79.9%) had non-psychotic disorders. Psychotic symptoms were assessed using the PRIME Screen-Revised (PS-R) questionnaire. The cohort was grouped according to gender, age (adolescents ≤ 21 years, adults > 21 years), and clinical diagnosis. Within the full sample, gender differences in psychotic symptoms were not significant, except that females appeared to have more severe symptoms of disorganized communication than males. However, gender differences began to appear at subgroup levels, after stratification by age and diagnosis. Female adolescents reported more severe psychotic symptoms than male adolescents, especially in the symptom of perceptual abnormalities, which refer to hallucinations. Different patterns and predictors were found to significantly discriminate between psychotic and non-psychotic disorders among age and gender groups. Our study highlights gender differences in the severity, frequency, and pattern of self-reported psychotic symptoms when screening in a first help-seeking population. Therefore, gender differences should be considered during psychotic symptoms screening.

Effects of irrelevant object structure on early attention deployment.

Event-related potential (ERP) studies have suggested that Gestalt principles or grouping factors in a visual scene modulate attention deployment in early visual processing. The present study examined the effects of an extrinsic grouping factor, region commonality, on early ERP spatial attention. Effects of sex were also explored, since the processing of task-irrelvant objects may differ between the sexes. Twenty-four participants were required to discriminate one side of rapidly-presented bilateral letters, and attention effects were indexed by hemispheric lateralization accroding to attended visual fields. In results, an early P1 attention effect (70-110 ms) increased when the letters were surrounded by an object, compared to the control stimulus without a complete object, and this result was more prominent in women than in men. The present study demonstrates that visual object and sex differences play a novel role at very early cortical stages of processing in attention deployment to a task-irrelevant visual structure.

Affective temperament, attachment style, and the psychological impact of the COVID-19 outbreak: an early report on the Italian general population.

The outbreak of COVID-19 is severely affecting mental health worldwide, although individual response may vary. This study aims to investigate the psychological distress perceived by the Italian general population during the early phase of the COVID-19 pandemic, and to analyze affective temperament and adult attachment styles as potential mediators. Through an online survey, we collected sociodemographic and lockdown-related information and evaluated distress, temperament, and attachment using the Kessler 10 Psychological Distress Scale (K10), the Temperament Evaluation of Memphis, Pisa, Paris and San Diego-Autoquestionnaire short version (TEMPS-A) and the Attachment Style Questionnaire (ASQ). In our sample (n = 500), 62% of the individuals reported no likelihood of psychological distress, whereas 19.4% and 18.6% displayed mild and moderate-to-severe likelihood. Cyclothymic (OR: 1.24; p < 0.001), depressive (OR: 1.52; p < 0.001) and anxious (OR: 1.58; p = 0.002) temperaments, and the ASQ "Need for approval" (OR: 1.08; p = 0.01) were risk factors for moderate-to-severe psychological distress compared to no distress, while the ASQ "Confidence" (OR: 0.89; p = 0.002) and "Discomfort with closeness" were protective (OR: 0.92; p = 0.001). Cyclothymic (OR: 1.17; p = 0.008) and depressive (OR: 1.32; p = 0.003) temperaments resulted as risk factors in subjects with moderate-to-severe psychological distress compared to mild distress, while the ASQ "Confidence" (OR: 0.92; p = 0.039) and "Discomfort with closeness" (OR: 0.94; p = 0.023) were protective. Our data indicated that a relevant rate of individuals may have experienced psychological distress following the COVID-19 outbreak. Specific affective temperament and attachment features predict the extent of mental health burden. To the best of our knowledge, these are the first data available on the psychological impact of the early phase of the COVID-19 pandemic on a sizeable sample of the Italian population. Moreover, our study is the first to investigate temperament and attachment characteristics in the psychological response to the ongoing pandemic. Our results provide further insight into developing targeted intervention strategies.

Problem Gambling in Greece: Prevalence and Risk Factors During the Financial Crisis.

In Greece no study has ever been conducted on the prevalence of problem gambling. Therefore, a cross-sectional survey was carried out amid the recession aiming to (1) estimate past year prevalence of problem gambling, (2) explore socio-economic and demographic differences among gamblers and non gamblers, (3) explore socio-economic and demographic differences among gamblers who started gambling prior and during the downturn and (4) identify its risk factors with a special interest in the influence of the recession. To this end, data emanating from a telephone and patron survey were combined. A random and representative sample of 3.404 people participated in the telephone survey and 2.400 in the patron survey. The interview schedule was the same in both studies. The presence of problem gambling was assessed with the Canadian Problem Gambling Index. Information on participants' socio-economic and demographic characteristics as well as their ways of dealing financially with the crisis were collected. Findings indicated that 2.4% of respondents met criteria for problem gambling. Male gender, minority status, living with family of origin, low educational level and low to zero income were found to constitute the risk factors of the disorder. Moreover, having started gambling during the recession increased the odds of suffering from problem gambling; however this finding was gender-specific. Thus, people end up in problem gambling through various pathways, with these trajectories being different for men and women. Any intervention should address the complexity of the issue and be tailored by gender.

CIS-Acting Allele-Specific Expression Differences Induced by Alcohol and Impacted by Sex as Well as Parental Genotype of Origin.

BACKGROUND: Alcohol use disorders (AUDs) are influenced by complex interactions between the genetics of the individual and their environment. We have previously identified hundreds of polygenic genetic variants between the selectively bred high- and low-alcohol drinking (HAD and LAD) rat lines. Here, we report allele-specific expression (ASE) differences, between the HAD2 and LAD2 rat lines. METHODS: The HAD2 and LAD2 rats, which have been sequenced, were reciprocally crossed to generate 10 litters of F1 progeny. For 5 of these litters, the sire was HAD2, and for the other 5 litters, the sire was a LAD2. From these 10 litters, 2 males and 2 females were picked from each F1 litter (N = 40 total). The F1 pups were divided, balancing for sex and direction of cross, into an alcohol (15%) versus a water control group. Alcohol drinking started in the middle of adolescence (~postnatal day 35) and lasted 9 weeks. At the end of these treatments, rats were euthanized, the nucleus accumbens was dissected, and RNA was processed for RNA-sequencing and ASE analyses. RESULTS: Analyses revealed that adolescent ethanol (EtOH) drinking, individual EtOH drinking levels, parentage, and sex-of-animal affected ASEs of about 300 genes. The identified genes included those associated with EtOH metabolism (e.g., Aldh2); neuromodulatory function (e.g., Cckbr, Slc6a7, and Slc1a1); ion channel activity (e.g., Kcnc3); and other synaptic and epigenetic functions. CONCLUSIONS: These data indicate that EtOH drinking differentially amplified paternal versus maternal allelic contribution to the transcriptome. We hypothesize that this was due, at least in part, to EtOH-induced changes in cis-regulation of polymorphisms previously identified between the HAD2 and LAD2 rat lines. This report highlights the complexity of gene-by-environment interactions mediating a genetic predisposition for, and/or the active development of, AUDs.

An analysis of proximal humerus morphology with special interest in stemless shoulder arthroplasty.

BACKGROUND: Shoulder arthroplasty evolution has resulted in the shortening of traditional stemmed humeral components. Newer stemless implants rely on structures that maintain fixation in the metaphyseal region of the proximal humerus. Whereas the overall morphology of the proximal humerus is well understood, the advent of stemless implants requires that additional geometric measures be assessed. This study's purpose was to introduce new anatomic measures to assist with the design of stemless implants. METHODS: Using computed tomography data from 98 subjects (nonarthritic [n = 41], B2 osteoarthritic [n = 26], and symmetric osteoarthritic [n = 31]), shifts in proximal canal direction, bounding diameters along the canal, and canal depth beneath the center of the humeral resection plane were quantified. Traditional articular aspect ratio terms (ie, resection diameter, humeral head height) were also quantified. All measures were reported relative to a humeral coordinate system relevant to stemless implants. RESULTS: Humeral depth, gender, and osteoarthritis were found to have effects on the measured parameters. Of these factors, gender was the most prominent, as men presented with significantly larger canal diameters and depths than women did (P < .001). Osteoarthritis had less of a significant impact on results (P < .001), with the attributed differences in canal path direction and articular aspect ratio being small in absolute value. Canal diameter was found to change significantly as a function of depth beneath the resection plane (P < .001). CONCLUSIONS: This work quantified 3 new morphologic terms relevant to proximal humerus stemless arthroplasty. Together, these outcome measures help define the spatial limits for stemless humeral arthroplasty in an implant-relevant coordinate system.

In vivo evaluation of some biophysical parameters of the facial skin of Indian subjects living in Mumbai. Part II: Variability with age and gender.

BACKGROUND: A previously published work explored the diversity of some biophysical parameters (colour, elasticity, sebum production, skin microrelief, etc.) of the skin of 1204 Indian women, differently aged, living in four Indian cities (Chennai, Delhi, Kolkata and Mumbai). The present work aimed at completing such research by focusing on possible gender-related differences in the same skin parameters, between Indian men and women living in the same Indian city (Mumbai). METHODS: A total of 297 Indian men, differently aged (18-70y), were recruited in Mumbai, completing the panel of 303 women who were previously recruited in this same city. The same instrumental measurements of facial skin colour and its homogeneity, its mechanical properties, the sebum production, skin pores size, skin relief, etc. as in the previous work, were conducted. RESULTS: Overall, the facial skin colour shows a darker complexion in men as compared to women, on forehead, ocular region, lips, chin and cheek. The skin colour unevenness, which increases with age, was found higher in men, as compared to women. At comparable age, women and men present a same density of skin pores, whereas those of men appear larger, up to 55y. The deepness of Crow's feet wrinkles does not significantly differ between genders. A lesser extensibility was found on the cheeks of men. In men, the sebum production was found significantly higher than that of women at ages above 40y. CONCLUSIONS: This work indicates some commonly shared age-related skin features between women and men from Mumbai, despite slight different characteristics such as skin pigmentation, forehead/cheek colour contrast, mechanical properties and sebum production.

Sex-dependent treatment of chronic EAE with partial MHC class II constructs.

BACKGROUND: One of the main challenges in treating multiple sclerosis (MS) is reversing the effects of accumulated damage in the central nervous system (CNS) of progressive MS subjects. While most of the available drugs for MS subjects are anti-inflammatory and thus are limited to relapsing-remitting MS subjects, it is not clear to what extent their effects are capable of inducing axonal repair and remyelination in subjects with chronic MS. METHODS: A chronic model of experimental autoimmune encephalomyelitis (EAE) was used to evaluate the potency of partial MHC (pMHC) class II constructs in treating progressive EAE. RESULTS: We demonstrated an estrogen receptor alpha (ERα)-dependent increased dose requirement for effective treatment of female vs. male mice using pMHC. Such treatment using 100-µg doses of RTL342M or DRα1-mMOG-35-55 constructs significantly reversed clinical severity and showed a clear trend for inhibiting ongoing CNS damage, demyelination, and infiltration of inflammatory cells into the CNS in male mice. In contrast, WT female mice required larger 1-mg doses for effective treatment, although lower 100-µg doses were effective in ovariectomized or ERα-deficient mice with EAE. CONCLUSIONS: These findings will assist in the design of future clinical trials using pMHC for treatment of progressive MS.

Social risky decision-making reveals gender differences in the TPJ: A hyperscanning study using functional near-infrared spectroscopy.

Previous neuroscience studies have investigated neural correlates of risky decision-making in a single-brain frame during pseudo social (predominantly non face-to-face) contexts. To fully understand the risky decision-making behavior in more natural social interactions, the present study employed a functional near-infrared spectroscopy (fNIRS) hyperscanning technique to simultaneously measure pairs of participants' fronto-temporal activations in a face-to-face gambling card-game. The intra-brain results revealed that both those who identified as males and as females showed higher activations in their mPFC and in the inferior parts of the frontopolar area, as well as in the tempo-parietal junction (TPJ) in cases involving higher versus lower risk. This is consistent with previous findings suggesting importance of the mentalizing network in decision tasks. The fNIRS results of inter-brain neural synchronization (INS) also revealed that males and females showed increased inter-brain coherence in the mPFC and dlPFC. Females, however, uniquely showed increased inter-brain coherence in the left TPJ. This INS result suggests that males may primarily depend on non-social cognitive ability to make a risky decision in a social interaction, while females may use both social and non-social cognitive abilities. The implications are also discussed for general topics of human interaction and two-person neuroscience.

Gender effect on public stigma changes towards psychosis in the Hong Kong Chinese population: a comparison between population surveys of 2009 and 2014.

PURPOSE: Public stigma is an important barrier to the recovery of patients with psychosis. The current study aimed to investigate the change in stigma towards psychosis and knowledge about psychosis between 2009 and 2014 among the Chinese population in Hong Kong, with a specific focus on gender role. METHODS: Random telephone survey of general population in Hong Kong was conducted in 2009 and 2014. Stigma was measured with the revised Link's Perceived Discrimination-Devaluation Scale (LPDDS). Logistic regression was used to explore the effect of time on the change of knowledge of psychosis, and linear regression was used to explore the effect of time on the change of stigma. Change of knowledge and stigma based on gender was specifically explored. RESULTS: In total, 1016 and 1018 subjects completed the survey in 2009 and 2014, respectively. Significantly, more people agreed with medication treatment for psychosis and fewer people had misunderstanding about psychosis. However, there was no significant change in stigma levels. Males were found to have a significant deterioration of stigma (B = 0.099, SE = 0.033, ß = 0.100, p = 0.003) but not females. Significantly, more males endorsed medication treatment for psychosis (χ 2 = 5.850, df = 1, p = 0.016) but no change for females (χ 2 = 1.401, df = 1, p = 0.238). CONCLUSIONS: Results of this study suggested that there was an improvement in the biological understanding of psychosis but no change of public stigma within the Hong Kong Chinese population. The specific role of gender in relation to stigma and level of knowledge about psychosis indicates that this should be a consideration in designing future anti-stigma campaigns.

Further evidence for population specific differences in the effect of DNA markers and gender on eye colour prediction in forensics.

The genetics of eye colour has been extensively studied over the past few years, and the identified polymorphisms have been applied with marked success in the field of Forensic DNA Phenotyping. A picture that arises from evaluation of the currently available eye colour prediction markers shows that only the analysis of HERC2-OCA2 complex has similar effectiveness in different populations, while the predictive potential of other loci may vary significantly. Moreover, the role of gender in the explanation of human eye colour variation should not be neglected in some populations. In the present study, we re-investigated the data for 1020 Polish individuals and using neural networks and logistic regression methods explored predictive capacity of IrisPlex SNPs and gender in this population sample. In general, neural networks provided higher prediction accuracy comparing to logistic regression (AUC increase by 0.02-0.06). Four out of six IrisPlex SNPs were associated with eye colour in the studied population. HERC2 rs12913832, OCA2 rs1800407 and SLC24A4 rs12896399 were found to be the most important eye colour predictors (p < 0.007) while the effect of rs16891982 in SLC45A2 was less significant. Gender was found to be significantly associated with eye colour with males having ~1.5 higher odds for blue eye colour comparing to females (p = 0.002) and was ranked as the third most important factor in blue/non-blue eye colour determination. However, the implementation of gender into the developed prediction models had marginal and ambiguous impact on the overall accuracy of prediction confirming that the effect of gender on eye colour in this population is small. Our study indicated the advantage of neural networks in prediction modeling in forensics and provided additional evidence for population specific differences in the predictive importance of the IrisPlex SNPs and gender.

Between-gender differences in vigilance do not necessarily lead to differences in foraging-vigilance tradeoffs.

When prey are time limited in their access to food, any trade-off involving time should ultimately affect their intake rate. In many herbivores, males and females experience different ecological pressures affecting their survival and reproduction because of differences in morphology, physiology and energy/nutrient requirements. If males and females have different vigilance strategies that affect their intake rates differently, they will suffer different foraging costs. This is particularly relevant in sexually monomorphic herbivores, where the two sexes have similar basal energy/nutrient requirements and risk of predation. We investigated how gender, reproductive status, age, group size, predation risk, and food biomass affected vigilance, intake rate, and their trade-off in a monomorphic species, the plains zebra (Equus quagga). Males were more vigilant than females, and lactating females were less vigilant than other females; the levels of vigilance were low (ca. 10 % of feeding time). The effects on time spent feeding, bite rates and intake rates were small and statistically not significant. Reproductive status did not affect the strength of the relationship between vigilance and intake rate, but intake rates increased with group size and, for adult females, were higher in tall grass. While gender and reproductive status were major drivers of vigilance, and group size and food biomass of the rate of food intake, males and females adjust their bite rates and food intake with vigilance in similar ways. Our results support the hypothesis that in monomorphic animals, males and females seem to make similar trade-offs (i.e. adjustments) between vigilance and intake rate.

Beetroot juice increase nitric oxide metabolites in both men and women regardless of body mass.

The nitrate (NO3(-)) present in beetroot juice (BJ) has been studied for its effect on the cardiovascular system by converting to nitric oxide (NO). In the present study, we evaluated the effect of BJ on the excretion of NO metabolites and its relationship with body mass in both men and women. NO metabolites - urinary NO3(-), nitrite (NO2(-)) and NOx were analyzed by using a high-performance liquid chromatography system. There were significant increases in urinary NO3(-), NO2(-) and NOx in BJ as compared to PLA (BJ without NO3(-)). No significant difference between men and women was observed in NO metabolites after BJ at any time point. There were no significant relationships between urinary NO3(-), NO2(-) and NOx and body mass in BJ intervention for both men and women. In conclusion, urinary NO metabolites after BJ consumption increases in similar manner between sexes regardless of body mass.

Gender-specific factors associated with shorter sleep duration at age 3 years.

Total sleep duration has been decreasing among children in the last decades. Short sleep duration (SSD) has been associated with deleterious health consequences, such as excess weight/obesity. Risk factors for SSD have already been studied among school-aged children and adolescents, but inconsistent results have been reported regarding possible gender differences. Studies reporting such relationships are scarce in preschoolers, despite the importance of this period for adopting healthy behaviour. We aimed to investigate factors associated with SSD in 3-year-old boys (n = 546) and girls (n = 482) in a French Mother-Child Cohort (EDEN Study). Children were born between 2003 and 2006 in two French university hospitals. Clinical examinations and parent self-reported questionnaires allowed us to collect sociodemographic (e.g. income, education, family situation, child-minding system), maternal [e.g. body mass index (BMI), parity, depression, breastfeeding duration] and child's characteristics (e.g. gender, birth weight, term, physical activity and TV viewing duration, food consumption, usual sleep time). Sleep duration/24-h period was calculated and SSD was defined as <12 h. Analyses were performed using logistic regression. The mean sleep duration was 12 h 35 ± 56 min, with 91% of the children napping. Patterns of risk factors associated with SSD differed according to gender. In addition to parental presence when falling asleep, short sleep duration was associated strongly positively with high BMI Z-score and TV viewing duration among boys and with familial home child-minding and lower scores on the 'fruits and vegetables' dietary pattern among girls. These results suggest either a patterning of parental behaviours that differs according to gender, or a gender-specific sleep physiology, or both.

Uncertainty in fast task-irrelevant perceptual learning boosts learning of images in women but not men.

A key tenet of models of reinforcement learning is that learning is most desirable in the times of maximum uncertainty. Here we examine the role of uncertainty in the paradigm of fast task-irrelevant perceptual learning (fast-TIPL), where stimuli that are consistently presented at relevant points in times (e.g., with task targets or rewards) are better encoded than when presented at other times. We manipulated two forms of uncertainty, expected uncertainty and unexpected uncertainty (Yu & Dayan, 2005), and compared fast-TIPL under uncertainty with fast-TIPL under no uncertainty. Results indicate a larger fast-TIPL effect under uncertainty than under no uncertainty without a difference between expected and unexpected uncertainty. However, interestingly, this effect of uncertainty on fast-TIPL was found in women but not in men. In men, equivalent fast-TIPL was observed under no uncertainty and uncertainty, whereas in women, confirming previous results (Leclercq & Seitz, 2012b), no fast-TIPL was observed in the no-uncertainty condition, but fast-TIPL was observed in the uncertainty conditions. We discuss how these results imply differences in attention or neuromodulatory processes between men and women.

Paradoxical gender effects in meat consumption across cultures.

Men tend to eat more meat than women, but it is not clear why. We tested three hypotheses in a cross-cultural design (20,802 individuals in 23 countries across four continents): that gender differences are (a) universal, (b) related to gender roles and thus weaker in countries with higher gender equality and human development, or (c) related to opportunities to express gender roles and thus stronger in countries with higher gender equality and human development. Across all countries, men tended to consume more meat than women. However, this difference increased significantly in countries with greater human development and gender equality. The paradoxical gender gap in meat consumption aligns with previous research that suggests greater differences in behavior across genders in contexts that are more developed and gender equal. We discuss implications for theories of culture and gender as well as practical implications for global meat reduction.

Diet Pattern Analysis in Alzheimer's Disease Implicates Gender Differences in Folate-B12-Homocysteine Axis on Cognitive Outcomes.

BACKGROUND & AIMS: Low plasma B12 and folate levels or hyperhomocysteinemia are related to cognitive impairment. This study explores the relationships among diet pattern, blood folate-B12-homocysteine levels, and cognition measurement in Alzheimer's disease (AD) while exploring whether a gender effect may exist. METHODS: This cross-sectional study enrolled 592 AD patients (246 males, 346 females) and the demographic data, blood biochemical profiles, Mini-Mental State Examination (MMSE), and a Food Frequency Questionnaire (FFQ) for quantitative assessment of dietary frequency were collected. Structural Equation Modeling (SEM) was employed to explore the associations among dietary patterns, blood profiles, and cognition. A least absolute shrinkage and selection operator regression model, stratified by gender, was constructed to analyze the weighting of possible confounders. RESULTS: Higher MMSE scores were related to higher frequencies of coffee/tea and higher educational levels, body mass index, and younger age. The SEM model revealed a direct influence of dietary frequencies (skimmed milk, thin pork, coffee/tea) and blood profiles (homocysteine, B12, and folate) on cognitive outcomes. At the same time, the influence of dietary pattern on cognition was not mediated by folate-B12-homocysteine levels. In males, a direct influence on the MMSE is attributed to B12, while in females, homocysteine is considered a more critical factor. CONCLUSIONS: Dietary patterns and blood profiles are both associated with cognitive domains in AD, and there are gender differences in the associations of dietary patterns and the levels of B12 and homocysteine. To enhance the quality of dietary care and nutritional status for individuals with dementia, our study results still require future validations with multi-center and longitudinal studies.