Mouse in vitro spermatogenesis is possible with classical organ culture methods, by placing the testis tissue at the interphase between culture medium and air. In this condition, however, a tissue piece tends to round up to be compact, whose central region suffers from shortage of nutrients and oxygen. In this study, the authors improved the culture condition by spreading each tissue thin and flat, by which they were able to get better access to the oxygen and nutrients.

This study aimed to investigate the association between sperm quality assessed by routine semen analysis and sperm DNA integrity assay.

EEG-based measures of neural tracking of natural running speech are becoming increasingly popular to investigate neural processing of speech and have applications in audiology. When the stimulus is a single speaker, it is usually assumed that the listener actively attends to and understands the stimulus. However, as the level of attention of the listener is inherently variable, we investigated how this affected neural envelope tracking. Using a movie as a distractor, we varied the level of attention while we estimated neural envelope tracking. We varied the intelligibility level by adding stationary noise. We found a significant difference in neural envelope tracking between the condition with maximal attention and the movie condition. This difference was most pronounced in the right-frontal region of the brain. The degree of neural envelope tracking was highly correlated with the stimulus signal-to-noise ratio, even in the movie condition. This could be due to residual neural resources to passively attend to the stimulus. When envelope tracking is used to measure speech understanding objectively, this means that the procedure can be made more enjoyable and feasible by letting participants watch a movie during stimulus presentation.

The present study combined fractional amplitude of low-frequency fluctuations (fALFF), regional homogeneity (ReHo), and functional connectivity (FC) to explore brain functional abnormalities in acute tinnitus patients (AT) with hearing loss.

Programmed cell death is an important biological process that plays an indispensable role in traumatic brain injury (TBI). Inhibition of necroptosis, a type of programmed cell death, is pivotal in neuroprotection and in preventing associated inflammatory responses. Our results showed that necroptosis occurred in human brain tissues after TBI. Necroptosis was also induced by controlled cortical impact (CCI) injury in a rat model of TBI and was accompanied by high translocation of high-mobility group box-1 (HMGB1) to the cytoplasm. HMGB1 was then passed through the impaired cell membrane to upregulate the receptor for advanced glycation end-products (RAGE), nuclear factor (NF)-κB, and inflammatory factors such as interleukin-6 (IL-6), interleukin-1 (IL-1β), as well as NACHT, LRR and PYD domains-containing protein 3 (NLRP3). Necroptosis was alleviated by necrostatin-1 and melatonin but not Z-VAD (a caspase inhibitor), which is consistent with the characteristic of caspase-independent signaling. This study also demonstrated that tumor necrosis factor, alpha-induced protein 3 (TNFAIP3, also known as A20) was indispensable for regulating and controlling necroptosis and inflammation after CCI. We found that a lack of A20 in a CCI model led to aggressive necroptosis and attenuated the anti-necroptotic effects of necrostatin-1 and melatonin.

Negative relationships with parents and peers are considered risk factors for depression in adolescence, yet not all adolescents perceiving negative social relationships develop depression. In line with neurobiological susceptibility to social context models, we examined how individual differences in neural processing of parental praise, a unique form of social reward, might explain variability in susceptibility to perceived maternal acceptance and peer victimization. During neuroimaging, 38 11- to 17-year-olds with a history of anxiety listened to audio clips of a parent (predominately mothers) providing personalized praise and neutral statements. Average activation during parental praise clips relative to neutral clips was extracted from several anatomically-defined reward-related regions-of-interest (ROIs): the subgenual anterior cingulate cortex, caudate nucleus, amygdala, nucleus accumbens, and insula. Moderation models included direct effects and interactions between neural activation to social reward, peer victimization, and maternal acceptance at the time of scanning on depressive symptoms 1 year later. Results showed a significant three-way interaction for the bilateral caudate such that peer victimization was associated with depressive symptoms only for individuals with higher caudate response to praise who perceived maternal acceptance as low. Consistent with neurobiological susceptibility to social context models, caudate activation to social reward could represent a neural marker that helps explain variability in adolescent sensitivity to social contexts. High caudate activation to praise could reflect a history of negative experiences with parents and/or peers that places youth at greater risk for depressive symptoms. Findings suggest that interactions between neural response to reward and salient social contexts may help us understand changes in depressive symptoms during a period of development marked by significant biopsychosocial change.

Wearable sensing technology is a new way to deliver corrective feedback. It is highly applicable to gait rehabilitation for persons with Parkinson's disease (PD) because feedback potentially engages spared neural function. Our study characterizes participants' motor adaptation to feedback signaling a deviation from their normal cadence during prolonged walking, providing insight into possible novel therapeutic devices for gait re-training. Twenty-eight persons with PD (15 with freezing, 13 without) and 13 age-matched healthy elderly (HE) walked for two 30-minute sessions. When their cadence varied, they heard either intelligent cueing (IntCue: bouts of ten beats indicating normal cadence) or intelligent feedback (IntFB: verbal instruction to increase or decrease cadence). We created a model that compares the effectiveness of the two conditions by quantifying the number of steps needed to return to the target cadence for every deviation. The model fits the short-term motor responses to the external step inputs (collected with wearable sensors). We found some significant difference in motor adaptation among groups and subgroups for the IntCue condition only. Both conditions were instead able to identify different types of responders among persons with PD, although showing opposite trends in their speed of adaptation. Increasing rather than decreasing the pace appeared to be more difficult for both groups. In fact, under IntFB the PD group required about seven steps to increase their cadence, whereas they only needed about three steps to decrease their cadence. However, it is important to note that this difference was not significant; perhaps future work could include more participants and/or more sessions, increasing the total number of deviations for analysis. Notably, a significant negative correlation, r = -0.57 (p-value = 0.008), was found between speed of adaptation and number of deviations during IntCue, but not during IntFB, suggesting that, for people who struggle with gait, such as those with PD, verbal instructions rather than metronome beats might be more effective at restoring normal cadence. Clinicians and biofeedback developers designing novel therapeutic devices could apply our findings to determine the optimal timing for corrective feedback, optimizing gait rehabilitation while minimizing the risk of cue-dependency.

Background: Metabolic syndrome (MS) is one of the major causes of coronary artery diseases (CAD). Gut microbiome diversity and its natural fermentation products are not only correlated with MS and CAD, but their correlations also appear to be stronger than the associations with traditional risk factors. Therefore, the aim of this study was to provide a new potential pathway for the natural fermentation product butyrate to improve MS and to examine whether it is associated with serum metabolic profiles and gut flora composition. Methods: C57BL/6J mice fed a high-fat diet (HFD) were treated with 400 mg/kg of sodium butyrate for 16 weeks. Blood and fecal samples were collected, and the metabolite concentrations and 16s rRNA were measured with liquid chromatography-MS and Illumina platform, respectively. The plasma differential metabolites and gut microbiome composition were analyzed with XCMS online and QIIME 2, respectively. Results: Gut microbiome-derived butyrate reduced glucose intolerance and insulin resistance, resisting HFD-induced increase in the relative abundance of f_Lachnospiraceae, f_Rikenellaceae, and f_Paraprevotellaceae. Meanwhile, sodium butyrate increased the levels of α-linolenate, all-trans-retinal, resolvin E1, and leukotriene in the plasma, and the differential pathways showed enrichment in mainly resolvin E biosynthesis, histidine degradation, lipoxin biosynthesis, and leukotriene biosynthesis. Moreover, sodium butyrate increased the levels of phosphorylated-adenosine 5'-monophosphate-activated protein kinase (p-AMPK) and facilitated glucose transporter member 4 (GLUT4) in the adipose tissue. Conclusion: Butyrate can induce AMPK activation and GLUT4 expression in the adipose tissue, improving cardiovascular disease (CVD)-related metabolic disorder, resisting HFD-induced gut microbiome dysbiosis, and promoting resolvin E1 and lipoxin biosynthesis. Oral supplement of the natural fermentation product butyrate can be a potential strategy for preventing CVD.

Black walnut (Juglans nigra L.) is an excellent source of health-promoting compounds. Consumption of black walnuts has been linked to many health benefits (e.g., anti-inflammatory) stemming from its phytochemical composition and medicinal properties, but these effects have not been systematically studied or characterized. In this study, potential anti-inflammatory compounds found in kernel extracts of 10 black walnut cultivars were putatively identified using a metabolomic profiling analysis, revealing differences in potential anti-inflammatory capacities among examined cultivars. Five cultivars were examined for activities in the human promonocytic cell line U-937 by evaluating the effects of the extracts on the expression of six human inflammatory cytokines/chemokines using a bead-based, flow cytometric multiplex assay. The methanolic extracts of these cultivars were added at four concentrations (0.1, 0.3, 1, and 10 mg/ml) either before and after the addition of lipopolysaccharide (LPS) to human U-937 cells to examine their effect on cytokine production. Results from cytotoxicity and viability assays revealed that the kernel extracts had no toxic effect on the U-937 cells. Of the 13 cytokines [interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein (MCP)-1, IL-6, IL-8, IL-10, IL-12, IL-17, IL-18, IL-23, IL-33, interferon (IFN)-α, IFN-γ] measured, only six were detected under the culture conditions. The production of the six detected cytokines by phorbol 12-myristate 13-acetate (PMA)-differentiated, LPS-stimulated U-937 was significantly inhibited by the kernel extracts from two cultivars Surprise and Sparrow when the extracts were added before the addition of LPS. Other cultivars (Daniel, Mystry, and Sparks) showed weak or no significant effects on cytokine production. In contrast, no inhibitory effect was observed on the production of cytokines by PMA-differentiated, LPS-stimulated U-937 when the kernel extracts were added after the addition of LPS. The findings suggest that the extracts from certain black walnut cultivars, such as Sparrow and Surprise, are promising biological candidates for potentially decreasing the severity of inflammatory disease.

Psychosis and/or aggression are common problems in dementia, and when severe or persistent, cause considerable patient distress and disability, caregiver stress, and early institutionalization. In 2005, the Food and Drug Administration (FDA) determined that atypical antipsychotics were associated with a significantly greater mortality risk compared to placebo, which prompted the addition of an FDA black-box warning. The American College of Neuropsychopharmacology (ACNP) White Paper, 2008, reviewed this issue and made clinical and research recommendations regarding the use of antipsychotics in dementia patients with psychosis and/or agitation. Increased mortality risk has also been described in cerebrovascular adverse events in elderly users of antipsychotics. In the present work, at the translational level, we used male 3xTg-AD mice (PS1M146V, APPSwe, tauP301L) at advanced stages of the disease reported to have worse survival than females, to study the behavioral effects of a low chronic dose of risperidone (0.1 mg/kg, s.c., 90 days, from 13 to 16 months of age) and its impact on long-term survival, as compared to mice with normal aging. Animals were behaviorally assessed for cognitive and BPSD (behavioral and psychological symptoms of dementia)-like symptoms in naturalistic and experimental conditions (open-field test, T-maze, social interaction, Morris water maze, and marble test) before and after treatment. Weight, basal glucose levels, and IPGTT (i.p. glucose tolerance test) were also recorded. Neophobia in the corner test was used for behavioral monitoring. Survival curves were recorded throughout the experiment until natural death. The benefits of risperidone were limited, both at cognitive and BPSD-like level, and mostly restricted to burying, agitation/vibrating tail, and other social behaviors. However, the work warns about a clear early mortality risk window during the treatment and long-lasting impact on survival. Reduced life expectancy and life span were observed in the 3xTg-AD mice, but total lifespan (36 months) recorded in C57BL/6 × 129Sv counterparts with normal aging was also truncated to 28 months in those with treatment. Sarcopenia at time of death was found in all groups, but was more severe in wild-type animals treated with risperidone. Therefore, the 3xTg-AD mice and their non-transgenic counterparts can be useful to delimitate critical time windows and for studying the physio-pathogenic factors and underlying causal events involved in this topic of considerable public health significance.

Sphingosine-1-phosphate receptor subtype 1 (S1P1) is essential for lymphocyte egress from lymphoid organs into systemic circulation and provides a well-defined drug target for autoimmune disorders. IMMH001, also called SYL930, is a specific S1P1/S1P4/S1P5 modulator. Here, we investigated the potential therapeutic effect of IMMH001 on rheumatoid arthritis (RA). IMMH001 rendered periphery blood lymphocytes insensitive to the egress signal from secondary lymphoid organs. Importantly, in both rat adjuvant-induced arthritis and collagen-induced arthritis models, IMMH001 treatment significantly inhibited the progression of RA and RA-associated histological changes in the joints of Sprague-Dawley rats, including hind paw swelling and arthritic index, and thus reduced the pathological score. Furthermore, IMMH001 markedly decreased proinflammatory cytokine and chemokine release from the damaged joints. These data demonstrated that IMMH001 is a promising drug candidate for RA treatment.

Atopic dermatitis (AD) is a frequent skin complication that is caused by unknown reasons. KHU-ATO-JIN-D (KAJD) is a new drug aimed at AD composed of a mixture of extracts from six plants known to have anti-inflammatory and antiallergic effects. This study investigated whether KAJD alleviates 2,4-dinitrochlorobenzene (DNCB)-induced AD in BALB/c mice and several immune cell types. We applied KAJD to DNCB-induced AD-like skin lesions in BALB/c mice, phorbol myristate acetate/ionomycin-stimulated human mast cells (HMC-1), and lipopolysaccharide (LPS)-stimulated macrophages and splenocytes. Histological, ELISA, PCR, and Western blot experiments were performed. The application of KAJD significantly attenuated the lesion severity and skin thickness and inhibited the infiltration of inflammatory cells, mast cells, and CD4+ T cells into the sensitized skin of mice. Reduced leukocyte numbers and proinflammatory cytokine and IgE levels were also observed in the sera of KAJD-treated mice. Moreover, in vitro studies demonstrated that KAJD treatment reduced the LPS-induced expression of proinflammatory cytokines and nitric oxide (NO) production in RAW 264.7 cells. The regulation of IL-4 and IL-6 mRNA and MAPK pathways was also detected in agonist-induced isolated splenocytes and HMC-1 cells by the addition of KAJD. Taken together, our results demonstrate that KAJD inhibits the development of DNCB-induced AD in BALB/c mice and in several immune cell types, suggesting that KAJD might be a useful therapeutic drug for the treatment of AD.

The use of smartphone apps for research and clinical care in mental health has become increasingly popular, especially within youth mental health. In particular, digital phenotyping, the monitoring of data streams from a smartphone to identify proxies for functional outcomes like steps, sleep, and sociability, is of interest due to the ability to monitor these multiple relevant indications of clinically symptomatic behavior. However, scientific progress in this field has been slow due to high heterogeneity among smartphone apps and lack of reproducibility. In this paper, we discuss how our division utilized a smartphone app to retrospectively identify clinically relevant behaviors in individuals with psychosis by measuring survey scores (symptom report), games (cognition scores), and step count (exercise levels). Further, we present specific cases of individuals and how the relevance of these data streams varied between them. We found that there was high variability between participants and that each individual's relevant behavior patterns relied heavily on unique data streams. This suggests that digital phenotyping has high potential to augment clinical care, as it could provide an efficient and individualized mechanism of identifying relevant clinical implications even if population-level models are not yet possible.

Background: Over the past few decades, bullying has been recognized as a considerable public health concern. Involvement in bullying is associated with poor long-term social and psychiatric outcomes for both perpetrators and targets of bullying. Despite this concerning prognosis, few studies have investigated possible neurobiological correlates of bullying involvement that may explain the long-term impact of bullying. Cortical thickness is ideally suited for examining deviations in typical brain development, as it has been shown to detect subtle differences in children with psychopathology. We tested associations between bullying involvement and cortical thickness using a large, population-based cohort. Methods: The study sample consisted of 2,602 participants from the Generation R Study. When children were 8 years old, parents and teachers reported on common forms of child bullying involvement (physical, verbal, and relational). Questions ascertained whether a child was involved as a perpetrator (n = 82), a target of bullying (n = 92), as a combined perpetrator and target of bullying (n = 47), or uninvolved in frequent bullying (n = 2,381). High-resolution structural MRI was conducted when children were 10 years of age. Cortical thickness estimates across the cortical mantle were compared among groups. Results: Children classified as frequent targets of bullying showed thicker cortex in the fusiform gyrus compared to those uninvolved in bullying (B = 0.108, p corrected < 0.001). Results remained consistent when adjusted for socioeconomic factors, general intelligence, and psychiatric symptoms. Children classified as frequent perpetrators showed thinner cortex in the cuneus region; however, this association did not survive stringent correction for multiple testing. Lastly, no differences in cortical thickness were observed in perpetrator-targets. Discussion: Bullying involvement in young children was associated with differential cortical morphology. Specifically, the fusiform gyrus, often involved in facial processing, showed thicker cortex in targets of frequent bullying. Longitudinal data are necessary to demonstrate the temporality of the underlying neurobiology associated with bullying involvement.

Anhedonia, the experience of diminished pleasure, is a core feature of major depressive disorder and is often present long before the diagnosis of depression. Most previous studies have investigated anhedonia with self-report measures of trait anhedonia or with behavioral paradigms using laboratory stimuli, and the real-time characteristics of hedonic processing in subclinical depression remain under-investigated. We used the experience sampling method to evaluate momentary experience of hedonic feelings in the context of daily life. Dysphoric (n = 49) and non-dysphoric (n = 51) college students completed assessments of their current positive affect (PA), as well as state anticipatory and consummatory pleasure, 3 or 4 times a day every day for 2 weeks. The results showed that dysphoric individuals reported less state anticipatory and consummatory pleasure compared with non-dysphoric individuals. Moreover, significant time-lagged associations between anticipatory pleasure and follow-up consummatory pleasure were found in the whole sample, after adjustment for current PA. The current findings thus hold considerable promise in advancing our understanding of anhedonia as well as the important role of state anticipatory pleasure in relation to depression.

The low professional insertion of psychologists in Brazilian sports teams, as well as the Sport Psychology course being seldom offered in undergraduate Psychology courses, may reflect in the current scenario of scientific research in Brazil. It is still not clear what Graduate Programs (GPs) have adopted directions regarding the development of studies in Sport and Exercise Psychology (SEP) research fields since an assessment or mapping of scientific knowledge production in this area has not yet been performed involving Exercise and Sport Science and Psychology GPs. This study aimed at investigating institutional research and their themes in SEP from these graduate programs. Studies were selected and retrieved from a national database (Sucupira Platform), that contains all registered researches from all Exercise and Sport Science (n = 31) and Psychology (n = 84) GPs in the country. Data were analyzed through R software using text mining techniques, latent semantic analysis and K-means clustering. Results revealed that research involving SEP is predominantly being developed at Exercise and Sport Science GPs (n = 171; p < 0.01) in comparison to psychology GPs (n = 39), mostly located in the south and southeast regions of Brazil. This research has focused on the effects of physical exercise and quality of life, while Psychology GPs have analyzed sport as associated with health and education, as a way to promote social support and to study sports' psychological aspects. It was concluded that Exercise and Sport Science GPs had the most significant contribution to SEP. Investigations were focused on the interface of exercise with quality of life, health and education, with gaps existing in programs advancing in the studies on sports and performance.

Stroke is one of the leading causes of disability all over the world. However, biomarkers for fast differential diagnosis of acute ischemic stroke (AIS) from vertigo or headache, remains lacking. Using a direct-infusion mass spectrometry method, it is possible to establish an efficient method for AIS differential diagnosis that requires only a few minutes. Thirty-eight clearly diagnosed AIS patients and 46 patients with a main complaint of vertigo were enrolled in this study. There was a total of 58 metabolites that were measured by our targeted metabolomics method, and the data were analyzed by pattern recognition algorithms. As a result, a clear classification between AIS and vertigo patients was achieved. Acylcarnitines are the major discriminating metabolites between the two groups. Arginine and its ratio, which is related to urea cycle metabolites, including arginine/ornithine and citrulline/arginine, also accounted for the classification. Interestingly, the levels of these metabolites were also found to be restored among recovering AIS patients (n = 11), which indicated that the metabolic alterations are possibly related to AIS development. Based on the characters from the data pattern reorganization, a novel biomarkers pattern was established using a binary logistic model, which contained arginine, arginine/ornithine, vaccenylcarnitine, and hydroxylbutyrylcarnitine. This biomarkers pattern achieved an area under the receiver operating characteristic curve of 0.89 for the differential diagnosis of AIS. Considering the efficiency and the diagnostic performance of the biomarkers pattern, our method has potential future use for the clinical application.

The applications of correct diagnostic approaches play a decisive role in timely containment of infectious diseases spread and mitigation of public health risks. Nevertheless, there is a need to update the diagnostics regularly to capture the new, emergent, and highly divergent viruses. Acute gastroenteritis of viral origin has been identified as a significant cause of mortality across the globe, with the more serious consequences seen at the extremes of age groups (young and elderly) and immune-compromised individuals. Therefore, significant advancements and efforts have been put in the development of enteric virus diagnostics to meet the WHO ASSURED criteria as a benchmark over the years. The Enzyme-Linked Immunosorbent (ELISA) and Polymerase Chain Reaction (PCR) are the basic assays that provided the platform for development of several efficient diagnostics such as real-time RT-PCR, loop-mediated isothermal amplification (LAMP), polymerase spiral reaction (PSR), biosensors, microarrays and next generation sequencing. Herein, we describe and discuss the applications of these advanced technologies in context to enteric virus detection by delineating their features, advantages and limitations.

The fungal cell wall is a structure in constant contact with the external environment. It confers shape to the cell and protects it from external threats. During host adaptation, the cell wall structure of fungal pathogens is continuously reshaped by the orchestrated action of numerous genes. These genes respond to environmental stresses and challenging growth conditions, influencing the infective potential of the fungus. Here, we aimed to identify cell wall biosynthesis-related genes that putatively encode virulence factors in Trichophyton rubrum. We used RNA-seq to examine the impact of two drugs, namely undecanoic acid, and acriflavine as well as the effects of the carbon source switching from glucose to keratin on T. rubrum cell wall metabolism. By using functional annotation based on Gene Ontology terms, we identified significantly differentially expressed cell wall-related genes in all stress conditions. We also exposed T. rubrum to osmotic and other cell wall stressors and evaluated the susceptibility and gene modulation in response to stress. The changes in the ambient environment caused continuous cell wall remodeling, forcing the fungus to undergo modulatory restructuring. The influence of the external challenges indicated a highly complex response pattern. The genes that were modulated simultaneously in the three stress conditions highlight potential targets for antifungal development.

Diel oscillations in primary and secondary production, growth, metabolic activity, and gene expression commonly occur in marine microbial communities in ocean surface waters. Diel periodicity of gene transcription has been demonstrated in photoautotrophic and heterotrophic microbes in both coastal and open ocean environments. To better define the spatiotemporal distribution and patterns of these daily oscillations, we investigated how diel periodicity in gene transcripts changed with depth from the surface waters to the upper mesopelagic. We postulated that diel oscillation of transcript abundances would diminish at greater depths across the collective microbial community due to decreasing light availability. The results showed that the number and total proportion of gene transcripts and taxa exhibiting diel periodicity were greatest in the shallow sunlit mixed layer, diminished rapidly with increasing depth to the base of the euphotic zone, and could not be detected in the mesopelagic. The results confirmed an overall decrease in microbial diel transcript oscillation with depth through the euphotic zone and suggested a relationship between abundance of diel oscillating transcripts and the daily integrated light exposure experienced by planktonic microbes in the water column. Local dissolved macronutrient concentration also appeared to influence the diel transcriptional patterns of specific microbial genes. The diminishing diel transcript oscillations found at increasing depths suggest that diel patterns of other microbial processes and interactions may likewise be attenuated at depth.