Large-scale animal model study uncovers altered brain pH and lactate levels as a transdiagnostic endophenotype of neuropsychiatric disorders involving cognitive impairment.

Increased levels of lactate, an end-product of glycolysis, have been proposed as a potential surrogate marker for metabolic changes during neuronal excitation. These changes in lactate levels can result in decreased brain pH, which has been implicated in patients with various neuropsychiatric disorders. We previously demonstrated that such alterations are commonly observed in five mouse models of schizophrenia, bipolar disorder, and autism, suggesting a shared endophenotype among these disorders rather than mere artifacts due to medications or agonal state. However, there is still limited research on this phenomenon in animal models, leaving its generality across other disease animal models uncertain. Moreover, the association between changes in brain lactate levels and specific behavioral abnormalities remains unclear. To address these gaps, the International Brain pH Project Consortium investigated brain pH and lactate levels in 109 strains/conditions of 2294 animals with genetic and other experimental manipulations relevant to neuropsychiatric disorders. Systematic analysis revealed that decreased brain pH and increased lactate levels were common features observed in multiple models of depression, epilepsy, Alzheimer's disease, and some additional schizophrenia models. While certain autism models also exhibited decreased pH and increased lactate levels, others showed the opposite pattern, potentially reflecting subpopulations within the autism spectrum. Furthermore, utilizing large-scale behavioral test battery, a multivariate cross-validated prediction analysis demonstrated that poor working memory performance was predominantly associated with increased brain lactate levels. Importantly, this association was confirmed in an independent cohort of animal models. Collectively, these findings suggest that altered brain pH and lactate levels, which could be attributed to dysregulated excitation/inhibition balance, may serve as transdiagnostic endophenotypes of debilitating neuropsychiatric disorders characterized by cognitive impairment, irrespective of their beneficial or detrimental nature.

Associations of dietary patterns and longitudinal brain-volume change in Japanese community-dwelling adults: results from the national institute for longevity sciences-longitudinal study of aging.

BACKGROUND: The association of dietary patterns and longitudinal changes in brain volume has rarely been investigated in Japanese individuals. We prospectively investigated this association in middle-aged and older Japanese community-dwelling adults. METHODS: Data with a 2-year follow-up from the sixth wave (July 2008 to July 2010; baseline) to the seventh (July 2010 to July 2012; follow-up) of the National Institute for Longevity Sciences-Longitudinal Study of Aging project were analyzed. Dietary intake was assessed using a 3-day dietary record, and longitudinal volume changes (%) in the total gray matter (TGM), total white matter, and frontal, parietal, occipital, temporal, and insular lobes were assessed using 3-dimensional T1 magnetic resonance imaging scans. Multiple factor analysis and hierarchical clustering revealed sex-specific dietary patterns. Associations between dietary patterns and annual brain-volume changes (%) were evaluated using general linear models adjusted for age, apoprotein E genotype, body mass index, medical history, lifestyle behaviors, socioeconomic factors, and energy intake. RESULTS: Among the 1636 participants (age: 40.3-89.2 years), three dietary patterns were determined for men (n = 815; Western; Vegetable-Fruit-Dairy; and Traditional Japanese diets) and women (n = 821; Western; Grain-Vegetable-Fruit; and Traditional Japanese diets). Compared to women following the Western diet, those on the Traditional Japanese diet had less TGM atrophy. Multivariable-adjusted ß (95% confidence interval) of the annual change (%) of TGM was - 0.145 (-0.287 to -0.002; P = 0.047), which correlated with reduced parietal lobe atrophy. No association between dietary pattern and brain atrophy was observed in men. CONCLUSIONS: Adherence to healthy dietary patterns, with higher consumption of whole grains, seafood, vegetables, fruits, mushrooms, soybean products, and green tea, potentially confers a protective effect against brain atrophy in middle-aged and older Japanese women but not in men. Further research to confirm these results and ascertain the underlying mechanisms is required. This study highlights the importance of sex-specific effects on the relationship between dietary patterns and brain health in diverse populations.

A novel model of divergent predictive perception.

Predictive processing theories state that our subjective experience of reality is shaped by a balance of expectations based on previous knowledge about the world (i.e. priors) and confidence in sensory input from the environment. Divergent experiences (e.g. hallucinations and synaesthesia) are likely to occur when there is an imbalance between one's reliance on priors and sensory input. In a novel theoretical model, inspired by both predictive processing and psychological principles, we propose that predictable divergent experiences are associated with natural or environmentally induced prior/sensory imbalances: inappropriately strong or inflexible (i.e. maladaptive) high-level priors (beliefs) combined with low sensory confidence can result in reality discrimination issues, a characteristic of psychosis; maladaptive low-level priors (sensory expectations) combined with high sensory confidence can result in atypical sensory sensitivities and persistent divergent percepts, a characteristic of synaesthesia. Crucially, we propose that whether different divergent experiences manifest with dominantly sensory (e.g. hallucinations) or nonsensory characteristics (e.g. delusions) depends on mental imagery ability, which is a spectrum from aphantasia (absent or weak imagery) to hyperphantasia (extremely vivid imagery). We theorize that imagery is critically involved in shaping the sensory richness of divergent perceptual experience. In sum, to predict a range of divergent perceptual experiences in both clinical and general populations, three factors must be accounted for: a maladaptive use of priors, individual level of confidence in sensory input, and mental imagery ability. These ideas can be expressed formally using nonparametric regression modeling. We provide evidence for our theory from previous work and deliver predictions for future research.

First evidence of widespread positivity to anticoagulant rodenticides in grey wolves (Canis lupus).

Second-generation Anticoagulant Rodenticides (ARs) can be critical for carnivores, due to their widespread use and impacts. However, although many studies explored the impacts of ARs on small and mesocarnivores, none assessed the extent to which they could contaminate large carnivores in anthropized landscapes. We filled this gap by exploring spatiotemporal trends in grey wolf (Canis lupus) exposure to ARs in central and northern Italy, by subjecting a large sample of dead wolves (n = 186) to the LC-MS/MS method. Most wolves (n = 115/186, 61.8 %) tested positive for ARs (1 compound, n = 36; 2 compounds, n = 47; 3 compounds, n = 16; 4 or more compounds, n = 16). Bromadiolone, brodifacoum and difenacoum, were the most common compounds, with brodifacoum and bromadiolone being the ARs that co-occurred the most (n = 61). Both the probability of testing positive for multiple ARs and the concentration of brodifacoum, and bromadiolone in the liver, systematically increased in wolves that were found at more anthropized sites. Moreover, wolves became more likely to test positive for ARs through time, particularly after 2020. Our results underline that rodent control, based on ARs, increases the risks of unintentional poisoning of non-target wildlife. However, this risk does not only involve small and mesocarnivores, but also large carnivores at the top of the food chain, such as wolves. Therefore, rodent control is adding one further conservation threat to endangered large carnivores in anthropized landscapes of Europe, whose severity could increase over time and be far higher than previously thought. Large-scale monitoring schemes for ARs in European large carnivores should be devised as soon as possible.

Differential Longitudinal Associations Between Domains of Cognitive Function and Physical Function: A 20-Year Follow-Up Study.

OBJECTIVES: Cognitive and physical functions are both associated with disability and death. Recent studies have addressed the relationship between cognitive declines and physical declines; however, whether various facets of cognition are diversely associated with specific physical functions is yet to be ascertained. The present work examines the longitudinal associations between fluid and crystallized cognitive functions (Gf and Gc) and physical functions. METHODS: The sample consisted of 863 community-dwelling older adults (baseline age 60-79 years) from the National Institute for Longevity Sciences-Longitudinal Study of Aging. The participants were tested on a set of Gf and Gc tests and physical tests (grip strength and gait speed). We ran a series of Multivariate Latent Growth Curve models. Specifically, we tested the relationship between cognitive and physical functions in terms of baseline performance (intercept) and rate of change (slope). RESULTS: The slope-slope correlations between Gf and physical function were large (grip strength r = 0.64 and gait speed r = 0.68, ps < .001). By contrast, the slope correlations between Gc and physical functions were weak (rs ≤ 0.31) and barely or marginally significant (ps ≤ .06). DISCUSSION: The results show that distinct domains of cognitive functions have different associations with physical functions. Namely, the aging-associated declines in the tested physical functions are robustly correlated with the declines in Gf, but are only weakly correlated with the declines in Gc. Therefore, Gc measures may be poor proxies for the patient's frailty and should be considered with caution in clinical assessment.

Fertility specialists' views, behavior, and attitudes towards the use of endometrial scratching in Italy.

BACKGROUND: Endometrial scratching (ES) or injury is intentional damage to the endometrium performed to improve reproductive outcomes for infertile women desiring pregnancy. Moreover, recent systematic reviews with meta-analyses and randomized controlled trials demonstrated that ES is not effective, data on the safety are limited, and it should not be recommended in clinical practice. The aim of the current study was to assess the view and behavior towards ES among fertility specialists throughout infertility centers in Italy, and the relationship between these views and the attitudes towards the use of ES as an add-on in their commercial setting. METHODS: Online survey among infertility centers, affiliated to Italian Society of Human Reproduction (SIRU), was performed using a detailed questionnaire including 45 questions with the possibility to give "closed" multi-choice answers for 41 items and "open" answers for 4 items. Online data from the websites of the infertility centers resulting in affiliation with the specialists were also recorded and analyzed. The quality of information about ES given on infertility centers websites was assessed using a scoring matrix including 10 specific questions (scored from 0 to 2 points), and the possible scores ranged from 0 to 13 points ('excellent' if the score was 9 points or more, 'moderate' if the score was between 5 and 8, and 'poor' if it was 4 points or less). RESULTS: The response rate was of 60.6% (43 questionnaires / 71 infertility SIRU-affiliated centers). All included questionnaires were completed in their entirety. Most physicians (~ 70%) reported to offer ES to less than 10% of their patients. The procedure is mainly performed in the secretory phase (69.2%) using pipelle (61.5%), and usually in medical ambulatory (56.4%) before IVF cycles to improve implantation (71.8%) without drugs administration (e.g., pain drugs, antibiotics, anti-hemorrhagics, or others) before (76.8%) or after (64.1%) the procedure. Only a little proportion of infertility centers included in the analysis proposes formally the ES as an add-on procedure (9.3%), even if, when proposed, the full description of the indications, efficacy, safety, and costs is never addressed. However, the overall information quality of the websites was generally "poor" ranging from 3 to 8 and having a low total score (4.7 ± 1.6; mean ± standard deviation). CONCLUSIONS: In Italy, ES is a procedure still performed among fertility specialists for improving the implantation rate in IVF patients. Moreover, they have a poor attitude in proposing ES as an add-on in the commercial setting.

No Appreciable Effect of Education on Aging-Associated Declines in Cognition: A 20-Year Follow-Up Study.

Education has been claimed to reduce aging-associated declines in cognitive function. Given its societal relevance, considerable resources have been devoted to this research. However, because of the difficulty of detecting modest rates of change, findings have been mixed. These discrepancies may stem from methodological shortcomings such as short time spans, few waves, and small samples. The present study overcame these limitations (N = 1,892, nine waves over a period of 20 years). We tested the effect of education level on baseline performance (intercept) and the rate of change (slope) in crystallized and fluid cognitive abilities (gc and gf, respectively) in a sample of Japanese adults. Albeit positively related to both intercepts, education had no impact on either the gc or the gf slope. Furthermore, neither intercept exhibited any appreciable correlation with either slope. These results thus suggest that education has no substantial role (direct or mediated) in aging-related changes in cognition.

Association between short-chain fatty acid intake and development of muscle strength loss among community-dwelling older Japanese adults.

BACKGROUND: Short-chain fatty acids (SCFAs) have been suggested to be associated with skeletal muscle mass maintenance. However, the role of dietary SCFAs in preserving muscle strength in the older population remains unclear. OBJECTIVES: To clarify the longitudinal association between the dietary intake of SCFAs and the development of low muscle strength in older community dwellers. METHODS: Data were obtained from the National Institute for Longevity Sciences-Longitudinal Study of Aging cohort. The participants included 441 men and 382 women who participated in the baseline survey (the fifth wave, between 2006 and 2008) and at least one follow-up examination (sixth to ninth waves, between 2008 and 2022) and were ≥60 years old and did not have low muscle strength (defined as a grip strength of <28 kg for men and <18 kg for women) at baseline. Baseline nutrient intakes were assessed with a 3-day dietary record. A generalized estimating equation was employed to estimate the odds ratio (OR) and 95 % confidence intervals (CIs) for low muscle strength per 1 standard deviation (SD) increase in the intake of SCFAs and other nutrients at baseline (adjusted for sex, age, follow-up time, baseline grip strength, physical activity, smoking, family income, education, and disease histories). RESULTS: The mean (SD) follow-up time and number were 7.8 (3.2) years and 3.2 (1.0) times, respectively. Approximately 8.1 % of the participants exhibited muscle strength loss in at least one follow-up assessment. The multivariate-adjusted OR (95 % CIs) was 0.77 (0.63-0.93) for each 1-SD increase in SCFA intake (268 mg/day), and the ORs for the highest through the lowest tertiles of SCFA intake were 1.00 (reference), 1.44 (0.95-2.17), and 1.83 (1.20-2.78), respectively (trend p = 0.005). The results remained significant after multivariate adjusting for energy or fat intake. CONCLUSION: Dietary intake of SCFAs may prevent muscle strength decline in community-dwelling older adults.

Cognitive Training: A Field in Search of a Phenomenon.

Considerable research has been carried out in the last two decades on the putative benefits of cognitive training on cognitive function and academic achievement. Recent meta-analyses summarizing the extent empirical evidence have resolved the apparent lack of consensus in the field and led to a crystal-clear conclusion: The overall effect of far transfer is null, and there is little to no true variability between the types of cognitive training. Despite these conclusions, the field has maintained an unrealistic optimism about the cognitive and academic benefits of cognitive training, as exemplified by a recent article (Green et al., 2019). We demonstrate that this optimism is due to the field neglecting the results of meta-analyses and largely ignoring the statistical explanation that apparent effects are due to a combination of sampling errors and other artifacts. We discuss recommendations for improving cognitive-training research, focusing on making results publicly available, using computer modeling, and understanding participants' knowledge and strategies. Given that the available empirical evidence on cognitive training and other fields of research suggests that the likelihood of finding reliable and robust far-transfer effects is low, research efforts should be redirected to near transfer or other methods for improving cognition.

Learning conversational dependency: Children's response using un in Japanese.

This study investigates how Japanese-speaking children learn interactional dependencies in conversations that determine the use of un, a token typically used as a positive response for yes-no questions, backchannel, and acknowledgement. We hypothesise that children learn to produce un appropriately by recognising different types of cues occurring in the immediately preceding turns. We built a set of generalised linear models on the longitudinal conversation data from seven children aged 1 to 5 years and their caregivers. Our models revealed that children not only increased their un production, but also learned to attend relevant cues in the preceding turns to understand when to respond by producing un. Children increasingly produced un when their interlocutors asked a yes-no question or signalled the continuation of their own speech. These results illustrate how children learn the probabilistic dependency between adjacent turns, and become able to participate in conversational interactions.

Effects of APOEɛ4 genotype on age-associated change in cognitive functions among Japanese middle-aged and older adults: A 20-year follow-up study.

BACKGROUND AND AIMS: Carriers of the apolipoprotein E ε4 allele (APOEɛ4) have an increased risk of developing dementia (e.g., Alzheimer's disease). However, it is less clear whether the APOEɛ4 might also be involved in cognitive aging among the non-clinical population of older adults. While some studies have suggested that the APOEɛ4 is related to accelerated cognitive decline in the normal aging process, others have failed to provide compelling evidence of such an impact. Notably, these discrepancies may depend on methodological shortcomings, including short time spans, few assessments, and small sample sizes. The present study overcomes the above limitations and aims to clarify the impact of the APOEɛ4 genotype on long-term longitudinal changes in cognitive functions in middle-aged and older adults in Japan. METHODS AND RESULTS: The data were retrieved from the National Institute for Longevity Sciences-Longitudinal Study of Aging (NILS-LSA) survey (N = 1832; 40 to 79 years of age at baseline). The participants were tested over nine waves covering a period of approximately 20 years. Latent Growth Curve (LGC) modeling was employed to test the impact of the interaction between APOEɛ4 status and age on several cognitive functions. Four tests of the WAIS-R were administered: Information, Similarities, Picture completion, and Digit Symbol Substitution Test (DSST). The results showed that the APOEɛ4 carriers experienced a more pronounced decline in the DSST (p = 0.001) and Similarities (p = 0.022) tests. A similar tendency was found in the Information test (p = 0.034). By contrast, no effect was found in the Picture completion test (p = 0.563). CONCLUSIONS: APOEɛ4 carriers seem to exhibit a steeper cognitive decline, which becomes apparent in old age. This effect is more robust in fluid cognitive skills (DSST) than crystallized cognitive skills (Information and Similarities). Overall, the APOEɛ4 genotype may be a significant risk factor in normal (i.e., non-clinical) cognitive aging.

LH increases the response to FSH in granulosa-lutein cells from sub/poor-responder patients in vitro.

STUDY QUESTION: Does LH addition to FSH in vitro recover the human primary granulosa lutein cell (hGLC) sub/poor-response? SUMMARY ANSWER: A picomolar concentration of LH may recover the FSH-induced cAMP and progesterone production of hGLC from sub/poor-responder women. WHAT IS KNOWN ALREADY: Clinical studies suggested that FSH and LH co-treatment may be beneficial for the ovarian response of sub/poor-responders undergoing ovarian stimulation during ART. STUDY DESIGN, SIZE, DURATION: hGLC samples from 286 anonymous women undergoing oocyte retrieval for ART were collected from October 2017 to February 2021. PARTICIPANTS/MATERIALS, SETTING, METHODS: hGLCs from women undergoing ovarian stimulation during ART were blindly purified, cultured, genotyped and treated in vitro by increasing concentrations of FSH (nM) ±0.5 nM LH. cAMP and progesterone levels produced after 3 and 24 h, respectively, were measured. In vitro data were stratified a posteriori, according to the donors' ovarian response, into normo-, sub- and poor-responder groups and statistically compared. The effects of LH addition to FSH were compared with those obtained by FSH alone in all the groups as well. MAIN RESULTS AND THE ROLE OF CHANCE: hGLCs from normo-responders were shown to have higher sensitivity to FSH treatment than sub-/poor-responders in vitro. Equimolar FSH concentrations induced higher cAMP (about 2.5- to 4.2-fold), and progesterone plateau levels (1.2- to 2.1-fold), in cells from normo-responder women than those from sub-/poor-responders (ANOVA; P < 0.05). The addition of LH to the cell treatment significantly increased overall FSH efficacy, indicated by cAMP and progesterone levels, within all groups (P > 0.05). Interestingly, these in vitro endpoints, collected from the normo-responder group treated with FSH alone, were similar to those obtained in the sub-/poor-responder group under FSH + LH treatment. No different allele frequencies and FSH receptor (FSHR) gene expression levels between groups were found, excluding genetics of gonadotropin and their receptors as a factor linked to the normo-, sub- and poor-response. In conclusion, FSH elicits phenotype-specific ovarian lutein cell response. Most importantly, LH addition may fill the gap between cAMP and steroid production patterns between normo- and sub/poor-responders. LIMITATIONS, REASONS FOR CAUTION: Although the number of experimental replicates is overall high for an in vitro study, clinical trials are required to demonstrate if the endpoints evaluated herein reflect parameters of successful ART. hGLC retrieved after ovarian stimulation may not fully reproduce the response to hormones of granulosa cells from the antral follicular stage. WIDER IMPLICATIONS OF THE FINDINGS: This in vitro assay may describe the individual response to personalize ART stimulation protocol, according to the normo-, sub- and poor-responder status. Moreover, this in vitro study supports the need to conduct optimally designed, randomized clinical trials exploring the personalized use of LH in assisted reproduction. STUDY FUNDING/COMPETING INTEREST(S): This study was supported by Merck KGaA. M.L. and C.C. are employees of Merck KGaA or of the affiliate Merck Serono SpA. Other authors have no competing interests to declare. TRIAL REGISTRATION NUMBER: N/A.

Humanized substitutions of Vmat1 in mice alter amygdala-dependent behaviors associated with the evolution of anxiety.

The human vesicular monoamine transporter 1 (VMAT1) harbors unique substitutions (Asn136Thr/Ile) that affect monoamine uptake into synaptic vesicles. These substitutions are absent in all known mammals, suggesting their contributions to distinct aspects of human behavior modulated by monoaminergic transmissions, such as emotion and cognition. To directly test the impact of these human-specific mutations, we introduced the humanized residues into mouse Vmat1 via CRISPR/Cas9-mediated genome editing and examined changes at the behavioral, neurophysiological, and molecular levels. Behavioral tests revealed reduced anxiety-related traits of Vmat1 Ile mice, consistent with human studies, and electrophysiological recordings showed altered oscillatory activity in the amygdala under anxiogenic conditions. Transcriptome analyses further identified changes in gene expressions in the amygdala involved in neurodevelopment and emotional regulation, which may corroborate the observed phenotypes. This knock-in mouse model hence provides compelling evidence that the mutations affecting monoaminergic signaling and amygdala circuits have contributed to the evolution of human socio-emotional behaviors.

Baseline situational analysis in Bangladesh, Jordan, Paraguay, the Philippines, Ukraine, and Zimbabwe for the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health.

INTRODUCTION: Mental, neurological and substance use conditions lead to tremendous suffering, yet globally access to effective care is limited. In line with the 13th General Programme of Work (GPW 13), in 2019 the World Health Organization (WHO) launched the WHO Special Initiative for Mental Health: Universal Health Coverage for Mental Health to advance mental health policies, advocacy, and human rights and to scale up access to quality and affordable care for people living with mental health conditions. Six countries were selected as 'early-adopter' countries for the WHO Special Initiative for Mental Health in the initial phase. Our objective was to rapidly and comprehensively assess the strength of mental health systems in each country with the goal of informing national priority-setting at the outset of the Initiative. METHODS: We used a modified version of the Program for Improving Mental Health Care (PRIME) situational analysis tool. We used a participatory process to document national demographic and population health characteristics; environmental, sociopolitical, and health-related threats; the status of mental health policies and plans; the prevalence of mental disorders and treatment coverage; and the availability of resources for mental health. RESULTS: Each country had distinct needs, though several common themes emerged. Most were dealing with crises with serious implications for population mental health. None had sufficient mental health services to meet their needs. All aimed to decentralize and deinstitutionalize mental health services, to integrate mental health care into primary health care, and to devote more financial and human resources to mental health systems. All cited insufficient and inequitably distributed specialist human resources for mental health as a major impediment. CONCLUSIONS: This rapid assessment facilitated priority-setting for mental health system strengthening by national stakeholders. Next steps include convening design workshops in each country and initiating monitoring and evaluation procedures.

The (decision) tree of fertility: an innovative decision-making algorithm in assisted reproduction technique.

PURPOSE: Several mathematical models have been developed to estimate individualized chances of assisted reproduction techniques (ART) success, although with limited clinical application. Our study aimed to develop a decisional algorithm able to predict pregnancy and live birth rates after controlled ovarian stimulation (COS) phase, helping the physician to decide whether to perform oocytes pick-up continuing the ongoing ART path. METHODS: A single-center retrospective analysis of real-world data was carried out including all fresh ART cycles performed in 1998-2020. Baseline characteristics, ART parameters and biochemical/clinical pregnancies and live birth rates were collected. A seven-steps systematic approach for model development, combining linear regression analyses and decision trees (DT), was applied for biochemical, clinical pregnancy, and live birth rates. RESULTS: Of fresh ART cycles, 12,275 were included. Linear regression analyses highlighted a relationship between number of ovarian follicles > 17 mm detected at ultrasound before pick-up (OF17), embryos number and fertilization rate, and biochemical and clinical pregnancy rates (p < 0.001), but not live birth rate. DT were created for biochemical pregnancy (statistical power-SP:80.8%), clinical pregnancy (SP:85.4%), and live birth (SP:87.2%). Thresholds for OF17 entered in all DT, while sperm motility entered the biochemical pregnancy's model, and female age entered the clinical pregnancy and live birth DT. In case of OF17 < 3, the chance of conceiving was < 6% for all DT. CONCLUSION: A systematic approach allows to identify OF17, female age, and sperm motility as pre-retrieval predictors of ART outcome, possibly reducing the socio-economic burden of ART failure, allowing the clinician to perform or not the oocytes pick-up.

Are sperm parameters able to predict the success of assisted reproductive technology? A retrospective analysis of over 22,000 assisted reproductive technology cycles.

BACKGROUND: An explosive increase in couples attending assisted reproductive technology has been recently observed, despite an overall success rate of about 20%-30%. Considering the assisted reproductive technology-related economic and psycho-social costs, the improvement of these percentages is extremely relevant. However, in the identification of predictive markers of assisted reproductive technology success, male parameters are largely underestimated so far. STUDY DESIGN: Retrospective, observational study. OBJECTIVES: To evaluate whether conventional semen parameters could predict assisted reproductive technology success. MATERIALS AND METHODS: All couples attending a single third-level fertility center from 1992 to 2020 were retrospectively enrolled, collecting all semen and assisted reproductive technology parameters of fresh cycles. Fertilization rate was the primary end-point, representing a parameter immediately dependent on male contribution. Pregnancy and live birth rates were considered in relation to semen variables. Statistical analyses were performed using the parameters obtained according to the World Health Organization manual editions used for semen analysis. RESULTS: Note that, 22,013 in vitro fertilization and intracytoplasmic sperm injection cycles were considered. Overall, fertilization rate was significantly lower in patients with abnormal semen parameters compared to normozoospermic men, irrespective of the World Health Organization manual edition. In the in vitro fertilization setting, both progressive motility (p = 0.012) and motility after capacitation (p = 0.002) significantly predicted the fertilization rate (statistical accuracy = 71.1%). Sperm motilities also predicted pregnancy (p < 0.001) and live birth (p = 0.001) rates. In intracytoplasmic sperm injection cycles, sperm morphology predicted fertilization rate (p = 0.001, statistical accuracy = 90.3%). Sperm morphology significantly predicted both pregnancy (p < 0.001) and live birth (p < 0.001) rates and a cut-off of 5.5% was identified as a threshold to predict clinical pregnancy (area under the curve = 0.811, p < 0.001). DISCUSSION: Interestingly, sperm motility plays a role in predicting in vitro fertilization success, while sperm morphology is the relevant parameter in intracytoplasmic sperm injection cycles. These parameters may be considered reliable tools to measure the male role on ART outcomes, potentially impacting the clinical management of infertile couples.

Survey on the Presence of Viruses of Economic and Zoonotic Importance in Avifauna in Northern Italy.

Wild birds play an important role in the circulation and spread of pathogens that are potentially zoonotic or of high economic impact on zootechnical production. They include, for example, West Nile virus (WNV), Usutu virus (USUV), avian influenza virus (AIV), and Newcastle disease virus (NDV), which, despite having mostly an asymptomatic course in wild birds, have a strong impact on public health and zootechnical production. This study investigated the presence of these viruses in several wild bird species from North Italy during the biennium 2019-2020. Wild birds derived from 76 different species belonging to 20 orders. Out of 679 birds, 27 were positive for WNV (lineage 2) with a prevalence of 4%; all birds were negative for USUV; one gull was positive for H13N6 influenza virus, and 12 samples were positive for NDV with a prevalence of 2%. Despite the low prevalence observed, the analyses performed on these species provide further data, allowing a better understanding of the diffusion and evolution of diseases of both economic and zoonotic importance.

Canine Distemper Outbreaks in Wild Carnivores in Northern Italy.

Canine distemper (CD) is a fatal, highly contagious disease of wild and domestic carnivores. In the Alpine territory, several outbreaks have occurred in the past few decades within wild populations. This study investigated the presence of canine distemper virus (CDV) infections in wild carnivores in Lombardy, relating to the different circulating genotypes. From 2018 to 2020, foxes, badgers, and martens collected during passive surveillance were subjected to necropsy and histological examination, showing classical signs and microscopic lesions related to CDV. Pools of viscera from each animal were analysed by molecular methods and immunoelectron microscopy. Total prevalences of 39.7%, 52.6%, and 14.3% were recorded in foxes, badgers, and stone martens, respectively. A phylogenetic analysis showed that the sequences obtained belonged to the European 1 lineage and were divided into two different clades (a and b) according to the geographical conformation of alpine valleys included in the study. Clade a was related to the European outbreaks originating from Germany in 2006-2010, while clade b was closely related to the CDV sequences originating from northeastern Italy during the 2011-2018 epidemic wave. Our results suggest that CDV is currently well adapted to wild carnivores, mostly circulating with subclinical manifestations and without severe impact on the dynamics of these populations.

Still no evidence that exergames improve cognitive ability: A commentary on Stanmore et al. (2017).

A recent meta-analysis (Stanmore et al. Neurosci. Biobehav. Rev. 78:34-43, 2017) claimed that exergames exert medium-size positive effects on people's overall cognitive function. The present article critically tests this claim. We argue that the meta-analysis reported inflated effect sizes mainly for three reasons: (a) some effect sizes were miscalculated; (b) there was an excessive amount of true heterogeneity; and (c) no publication-bias-corrected estimates were provided. We have thus recalculated the effect sizes and reanalyzed the data using a more robust approach and more sophisticated techniques. Compared to Stanmore's et al., our models show that: (a) the overall effect sizes are substantially smaller; (b) the amount of true heterogeneity, when any, is much lower; and (c) the publication-bias analyses suggest that the actual effect of exergames on overall cognitive function is slim to null. Therefore, the cognitive benefits of exergames are far from being established.

Cognitive and academic benefits of music training with children: A multilevel meta-analysis.

Music training has repeatedly been claimed to positively impact children's cognitive skills and academic achievement (literacy and mathematics). This claim relies on the assumption that engaging in intellectually demanding activities fosters particular domain-general cognitive skills, or even general intelligence. The present meta-analytic review (N = 6,984, k = 254, m = 54) shows that this belief is incorrect. Once the quality of study design is controlled for, the overall effect of music training programs is null ([Formula: see text] ≈ 0) and highly consistent across studies (τ2 ≈ 0). Results of Bayesian analyses employing distributional assumptions (informative priors) derived from previous research in cognitive training corroborate these conclusions. Small statistically significant overall effects are obtained only in those studies implementing no random allocation of participants and employing non-active controls ([Formula: see text] ≈ 0.200, p < .001). Interestingly, music training is ineffective regardless of the type of outcome measure (e.g., verbal, non-verbal, speed-related, etc.), participants' age, and duration of training. Furthermore, we note that, beyond meta-analysis of experimental studies, a considerable amount of cross-sectional evidence indicates that engagement in music has no impact on people's non-music cognitive skills or academic achievement. We conclude that researchers' optimism about the benefits of music training is empirically unjustified and stems from misinterpretation of the empirical data and, possibly, confirmation bias.