MIR137 polygenic risk for schizophrenia and ephrin-regulated pathway: Role in lateral ventricles and corpus callosum volume.

Background/Objective. Enlarged lateral ventricle (LV) volume and decreased volume in the corpus callosum (CC) are hallmarks of schizophrenia (SZ). We previously showed an inverse correlation between LV and CC volumes in SZ, with global functioning decreasing with increased LV volume. This study investigates the relationship between LV volume, CC abnormalities, and the microRNA MIR137 and its regulated genes in SZ, because of MIR137's essential role in neurodevelopment. Methods. Participants were 1224 SZ probands and 1466 unaffected controls from the GENUS Consortium. Brain MRI scans, genotype, and clinical data were harmonized across cohorts and employed in the analyses. Results. Increased LV volumes and decreased CC central, mid-anterior, and mid-posterior volumes were observed in SZ probands. The MIR137-regulated ephrin pathway was significantly associated with CC:LV ratio, explaining a significant proportion (3.42 %) of CC:LV variance, and more than for LV and CC separately. Other pathways explained variance in either CC or LV, but not both. CC:LV ratio was also positively correlated with Global Assessment of Functioning, supporting previous subsample findings. SNP-based heritability estimates were higher for CC central:LV ratio (0.79) compared to CC or LV separately. Discussion. Our results indicate that the CC:LV ratio is highly heritable, influenced in part by variation in the MIR137-regulated ephrin pathway. Findings suggest that the CC:LV ratio may be a risk indicator in SZ that correlates with global functioning.

Effect of 200 µg of gonadorelin hydrochloride at the first GnRH of a CIDR Synch program on ovulation rate and pregnancies per AI in Holstein heifers.

The initial ovulatory response during synchronization programs is often low in dairy heifers, largely due to follicular dynamics and hormonal dynamics. Specifically, the progesterone concentration (P4) at the time of the first GnRH treatment in a breeding program can influence the LH response, often resulting in a suboptimal ovulatory response. The objective of this study was to determine the effect of the highest label dose 200 µg (100 µg vs. 200 µg) of GnRH (50 µg gonadorelin hydrochloride per mL; Factrel®; Zoetis Inc. Madison, NJ) at the first GnRH of a 6-d CoSynch plus P4 device program on ovulatory response and pregnancy per AI (P/AI) in first service in Holstein heifers. A total of 1308 Holstein heifers were randomly allocated at the beginning of a 6-d CIDR-Synch program, Day 0, to receive either i.m. treatment of 100 µg (2CC, n = 655) or 200 µg (4CC, n = 653) of GnRH. Also, at Day 0, heifers received an intravaginal insert with 1.38 g of P4 (Eazi-Breed CIDR® Cattle Insert; Zoetis Inc., Madison, NJ). On Day 6, the insert was removed, and i.m. treatment of 25 mg of PGF2α (12.5 mg dinoprost tromethamine/mL; Lutalyse® HighCon Injection Zoetis) was administered. On Day 7, a second i.m. treatment of 25 mg of PGF2α was given, followed on Day 9 by concurrent i.m. treatment of 100 µg of GnRH and timed AI (TAI). A subset of 396 heifers had their ovaries scanned to evaluate ovulatory response, and blood samples were collected to measure the serum concentration of P4 at Day 0 and Day 6 of the study. The P4 concentrations at Day 0 were categorized as Low (≤3ng/mL) or High (>3ng/mL). The ovulatory response was greater for heifers receiving 4CC than 2CC at Day 0 (54.7% vs. 42.8%). The ovulatory response was greater for Low P4 than High P4 at Day 0 (54.3% vs. 37.8%). However, there was not an interaction between treatment and P4 concentrations (Low P4 2CC = 48.6% vs. High P4 2CC = 30.0%; Low P4 4CC = 60.0% vs. High P4 4CC = 45.5%). The ROC curve analysis indicates that P4 concentrations at Day 0 treatment could predict the ovulatory response, although the area under the curve was only 0.6. As expected, heifers that ovulated had increased P/AI (No = 55.6% vs. Yes = 67.7%); however, there was no effect of treatment on P/AI (2CC = 63.3% vs. 4CC = 59.6%), nor interactions between treatment and ovulation and treatment and P4 (HIGH vs LOW) for pregnancy outcomes. In summary, P4 concentration and increasing the dose of GnRH at Day 0 positively impacted ovulatory response in Holstein heifers. However, there was no interaction between treatment and P4 on ovulation and no subsequent impact of GnRH dose on P/AI.

Nutrition supplementation plus standard of care versus standard of care alone or standard of care plus unconditional cash transfer in the prevention of chronic malnutrition in Southern Angola: study protocol for the MuCCUA study, a cluster randomized controlled trial.

BACKGROUND: Chronic malnutrition is a condition associated with negative impacts on physical and cognitive development. It is multi-causal and can start very early in life, already in utero, thus it is especially challenging to find appropriate interventions to tackle it. The government of Angola is implementing a standard of care program with potential to prevent it, and the provision of cash transfers and the supplementation with small quantity lipid-based nutrients (SQ-LNS) are also promising interventions. We aimed to evaluate the impact of the standard of care program alone and of the standard of care plus a cash transfer intervention in the lineal growth of children less than 2 years old and compare it to the effectiveness of a nutrition supplementation plus standard of care program in Southern Angola. METHODS/DESIGN: The three-arm parallel cluster randomised controlled trial is set in four communes of Huila and Cunene provinces. Clusters are villages or neighbourhoods with a population around 1075 people. A total of twelve clusters were selected per arm and forty pregnant women are expected to be recruited in each cluster. Pregnant women receive the standard of care alone, or the standard of care plus unconditional cash transfer or plus nutritional supplementation during the first 1000 days, from pregnancy to the child reaching 24 months. The primary outcome is the prevalence of stunting measured as height-for-age Z-score (HAZ) < -2 in children below 2 years. Impact will be assessed at 3, 6, 12, 18 and 24 months of children's age. Secondary outcomes include mortality, morbidity, caring, hygiene and nutrition behaviours and practices, and women and children's dietary diversity. Quantitative data are also collected on women's empowerment, household food security, expenditure and relevant clinical and social events at baseline, endline and intermediate time points. DISCUSSION: The results will provide valuable information on the impact of the standard of care intervention alone as well as combined with an unconditional cash transfer intervention compared to a nutrition supplementation plus standard of care intervention, carried out during the first 1000 days, in the children´s growth up to 2 years and related outcomes in Southern Angola. TRIAL REGISTRATION: Clinical Trials NCT05571280. Registered 7 October 2022.

Effect of rumen-protected choline on dairy cow metabolism, immunity, lactation performance, and vaginal discharge microbiome.

Rumen-protected choline (RPC) promotes benefits in milk production, immunity, and health in dairy cows by optimizing lipid metabolism during transition period management and early lactation. However, the RPC success in dairy cows depends on choline bioavailability, which is affected by the type of protection used in rumen-protected choline. Therefore, our objectives were to determine the effects of a novel RPC on dry matter intake (DMI), identify markers of metabolism and immunity, and evaluate lactation performance. Dry Holstein (n = 48) cows at 245 ± 3 d of gestation were blocked by parity and assigned to control or RPC treatment within each block. Cows enrolled in the RPC treatment received 15 g/d of CholiGEM (Kemin Industries, Cavriago RE, Italy) from 21 d prepartum and 30 g/d of CholiGEM from calving to 21 d postpartum. During the transition period, DMI was measured daily, and blood was sampled weekly for energy-related metabolites such as ß-hydroxybutyrate (BHB), glucose, and nonesterified fatty acids (NEFA), as well as immune function markers such as haptoglobin (Hp) and lipopolysaccharide-binding protein (LPB). Vaginal discharge samples were collected at the calving and 7 d postpartum and stored in microcentrifuge tubes at -80°C until 16S rRNA sequencing. The main responses of body condition score, body weight, DMI, milk yield, milk components, and immune function markers were analyzed using the GLIMMIX procedure of SAS with the effects of treatment, time, parity, and relevant covariates added to the models. The relative abundance of microbiome α-diversity was evaluated by 3 indexes (Chao1, Shannon, and Simpson) and ß-diversity by principal coordinate analysis and permutational multivariate ANOVA. We found no differences in DMI in the pre- and postpartum periods. Cows fed RPC increased the yields of energy- and 3.5% fat-corrected milk and fat yield in primiparous and multiparous cows, with an interaction between treatment and parity for these lactation variables. However, we found no differences in milk protein and lactose up to 150 DIM between treatments. Glucose, NEFA, and BHB had no differences between the treatments. However, RPC decreased BHB numerically (control = 1.07 ± 0.13 vs. RPC = 0.63 ± 0.13) in multiparous on the third week postpartum and tended to reduce the incidence of subclinical ketosis (12.7% vs. 4.2%). No effects for Hp and LPB were found in cows fed RPC. Chao1, Shannon, and Simpson indexes were lower at calving in the RPC treatment than in the Control. However, no differences were found 7 d later for Chao1, Shannon, and Simpson indexes. The vaginal discharge microbiome was altered in cows fed RPC at 7 d postpartum. Fusobacterium, a common pathogen associated with metritis, was reduced in cows fed RPC. Rumen-protected choline enhanced lactation performance and health and altered the vaginal discharge microbiome which is a potential proxy for uterine healthy in dairy cows. The current study's findings corroborate that RPC is a tool to support adaptation to lactation and shed light on opportunities for further research in reproductive health.

Geographical trends for automatic milking systems research in non-pasture-based dairy farms: A scoping review.

Automatic milking system (AMS) adoption in the United States is trending upward, with issues such as lower availability and increased cost of labor being factors frequently listed as motives for AMS implementation. In addition, more interest in precision dairy farming by the new generation of farmers may also help increase AMS adoption. The objective of this scoping review was to characterize the nature of the literature investigating non-pasture-based AMS and the opportunities and challenges for future research. The eligibility criteria included studies published in or after the year 2000, with full text in English, of at least 500 words, examining various outcomes related to AMS in non-pasture-based dairy farms. Six electronic databases were searched: Biosis (Web of Science), CAB Abstracts (CAB Direct), Medline (PubMed), PubAg, AGRIS (FAO), and Scopus (Elsevier). The review focused on studies with objectives, characteristics, farms, and AMS information. A total of 4,292 titles and abstracts were screened, and 536 studies were finally included. Most of the studies were conducted in Europe (73.5%), among commercial herds (67.9%), comprising Holstein cows (57.7%), using Lely and DeLaval brands (45.4% vs. 39.7%), with free-flow traffic (52.7%). The main research topics investigated were milk production, milk composition, and AMS efficiency, followed by behavior and welfare, health disorders (especially mastitis), and nutrition in Europe and other regions. At the same time, in the United States, trends were similar, except for nutrition. Since 2016, there has been an increased interest in studies on energy and water consumption, technological development, environment (enteric emissions), reproduction, genetics, and longevity or culling. However, the small number of studies and unclear characterization of what is optimum for reproductive management, other health disorders, economics, and water and energy consumption suggest a need for future research.

From farm to fork and beyond! UV enhances Aryl hydrocarbon receptor-mediated activity of cruciferous vegetables in human intestinal cells upon colonic fermentation.

While the "farm to fork" strategy ticks many boxes in the sustainability agenda, it does not go far enough in addressing how we can improve crop nutraceutical quality. Here, we explored whether supplementary ultraviolet (UV) radiation exposure during growth of broccoli and Chinese cabbage can induce bioactive tryptophan- and glucosinolate-specific metabolite accumulation thereby enhancing Aryl hydrocarbon receptor (AhR) activation in human intestinal cells. By combining metabolomics analysis of both plant extracts and in vitro human colonic fermentation extracts with AhR reporter cell assay, we reveal that human colonic fermentation of UVB-exposed Chinese cabbage led to enhanced AhR activation in human intestinal cells by 23% compared to plants grown without supplementary UV. Thus, by exploring aspects beyond "from farm to fork", our study highlights a new strategy to enhance nutraceutical quality of Brassicaceae, while also providing new insights into the effects of cruciferous vegetables on human intestinal health.

Comparison of visual and passive acoustic estimates of beaked whale density off El Hierro, Canary Islands.

Passive acoustic monitoring (PAM) offers considerable potential for density estimation of cryptic cetaceans, such as beaked whales. However, comparative studies on the accuracy of PAM density estimates from these species are lacking. Concurrent, low-cost drifting PAM, with SoundTraps suspended at 200 m depth, and land-based sightings, were conducted off the Canary Islands. Beaked whale density was estimated using a cue-count method, with click production rate and the probability of click detection derived from digital acoustic recording tags (DTags), and distance sampling techniques, adapted to fixed-point visual surveys. Of 32 870 detections obtained throughout 206 h of PAM recordings, 68% were classified as "certain" beaked whale clicks. Acoustic detection probability was 0.15 [coefficient variation (CV) 0.24] and click production rate was 0.46 clicks s - 1 (CV 0.05). PAM density estimates were in the range of 21.5 or 48.6 whales per 1000 km2 [CV 0.50 or 0.44, 95% confidence interval (CI) 20.7-22.4 or 47-50.9), depending on whether "uncertain" clicks were considered. Density estimates from concurrent sightings resulted in 33.7 whales per 1000 km2 (CV 0.77, 95% CI 8.9-50.5). Cue-count PAM methods under application provide reliable estimates of beaked whale density, over relatively long time periods and in realistic scenarios, as these match the concurrent density estimates obtained from visual observations.

Drivers of human-wildlife impact events involving mammals in Southeastern Brazil.

Annually millions of animals are killed as a result of human-wildlife impacts. Each year the NGO Associação Mata Ciliar (NGOMC), in Southeastern Brazil, receives and rehabilitates thousands of animals. We evaluated how natural and anthropogenic characteristics affect the risk of different types of human-wildlife impacts for mammals that arrive at the NGOMC; and explore the relationship between both the animal's size and the type of human-wildlife impact event, survival rates and the likelihood that these animals can be fully rehabilitated. To test our hypotheses regarding the drivers and consequences of the total number of human-wildlife impact events, traffic collisions, electrocutions, and requested removals, we used records of the mammals that arrived at the NGOMC between 2012 and 2018, and obtained data on environmental attributes and anthropogenic factors at the municipality level, as well as species weights. The total number of human-wildlife impact events and of requested removals were both positively correlated with deforestation rate and urban area. The number of traffic collisions was positively related to the number of fires. Municipalities with larger urban areas were more likely to have at least one electrocuted mammal. Temporally, the number of fires two months before was positively correlated with the number of human-wildlife impact events. Traffic collisions and electrocutions more frequently resulted in the death of the animal, than did other events. Animals that died were heavier on average than those that remained in captivity or were successfully released back into the wild. We conclude that human-wildlife impact event rates should decline with lower rates of deforestation, less anthropogenic fires and the adoption of other specific measures to avoid both traffic collisions with fauna and electrocutions.

Classification of first-episode psychosis using cortical thickness: A large multicenter MRI study.

Machine learning classifications of first-episode psychosis (FEP) using neuroimaging have predominantly analyzed brain volumes. Some studies examined cortical thickness, but most of them have used parcellation approaches with data from single sites, which limits claims of generalizability. To address these limitations, we conducted a large-scale, multi-site analysis of cortical thickness comparing parcellations and vertex-wise approaches. By leveraging the multi-site nature of the study, we further investigated how different demographical and site-dependent variables affected predictions. Finally, we assessed relationships between predictions and clinical variables. 428 subjects (147 females, mean age 27.14) with FEP and 448 (230 females, mean age 27.06) healthy controls were enrolled in 8 centers by the ClassiFEP group. All subjects underwent a structural MRI and were clinically assessed. Cortical thickness parcellation (68 areas) and full cortical maps (20,484 vertices) were extracted. Linear Support Vector Machine was used for classification within a repeated nested cross-validation framework. Vertex-wise thickness maps outperformed parcellation-based methods with a balanced accuracy of 66.2% and an Area Under the Curve of 72%. By stratifying our sample for MRI scanner, we increased generalizability across sites. Temporal brain areas resulted as the most influential in the classification. The predictive decision scores significantly correlated with age at onset, duration of treatment, and positive symptoms. In conclusion, although far from the threshold of clinical relevance, temporal cortical thickness proved to classify between FEP subjects and healthy individuals. The assessment of site-dependent variables permitted an increase in the across-site generalizability, thus attempting to address an important machine learning limitation.

The influence of risk factors on the onset and outcome of psychosis: What we learned from the GAP study.

The GAP multidisciplinary study carried out in South London, recruited 410 first episode of psychosis patients and 370 controls; the aim was to elucidate the multiple genetic and environmental factors influencing the onset and outcome of psychosis. The study demonstrated the risk increasing effect of adversity in childhood (especially parental loss, abuse, and bullying) on onset of psychosis especially positive symptoms. Adverse life events more proximal to onset, being from an ethnic minority, and cannabis use also played important roles; indeed, one quarter of new cases of psychosis could be attributed to use of high potency cannabis. The "jumping to conclusions" bias appeared to mediate the effect of lower IQ on vulnerability to psychosis. We confirmed that environmental factors operate on the background of polygenic risk, and that genetic and environment act together to push individuals over the threshold for manifesting the clinical disorder. The study demonstrated how biological pathways involved in the stress response (HPA axis and immune system) provide important mechanisms linking social risk factors to the development of psychotic symptoms. Further evidence implicating an immune/inflammatory component to psychosis came from our finding of complement dysregulation in FEP. Patients also showed an upregulation of the antimicrobial alpha-defensins, as well as differences in expression patterns of genes involved in NF-κB signaling and Cytokine Production. Being of African origin not only increased risk of onset but also of a more difficult course of illness. The malign effect of childhood adversity predicted a poorer outcome as did continued use of high potency cannabis.

Small for gestational age very preterm infants present a higher risk of developing bronchopulmonary dysplasia.

INTRODUCTION: Several studies assessed the influence of a low birth weight on bronchopulmonary dysplasia (BPD), but not all could find a significant association. Our aim was to assess the association between low birth weight and BPD in preterm infants, prospectively recruited at 11 level III Portuguese neonatal centers. METHODS: Obstetrical and neonatal data on mothers and preterm infants with gestational ages between 24 and 30 weeks, born during 2015 and 2016 after a surveilled pregnancy, were analyzed. Neonates were considered small for gestational age (SGA) when their birthweight was below the 10th centile of Fenton's growth chats and BPD was defined as the dependency for oxygen therapy until 36 weeks of corrected age. Statistical analysis was performed using IBM SPSS® statistics 23 and a p-value <0.05 was considered statistically significant. RESULTS: Out of 614, a total of 494 preterm infants delivered from 410 women were enrolled in the study; 40 (8.0%) infants with SGA criteria. SGA were more often associated with a single pregnancy, had greater use of antenatal corticosteroids, increased prevalence of gestational hypertensive disorders, C-section, rupture of membranes below 18 hours, rate of intubation in the delivery room, use of surfactant treatment, oxygen therapy, mechanical ventilation need, BPD, cystic periventricular leukomalacia, nosocomial sepsis and pneumonia; had lower prevalence of chorioamnionitis, and lower Apgar scores. The multivariate analysis by logistic regression, adjusted for BPD risk factors revealed a significant association between SGA and BPD: OR = 5.2 [CI: 1.46-18.58]; p = 0.01. CONCLUSION: The results of this study increase the scientific evidence that SGA is an independent risk factor for BPD.

Mycobacterium marinum lymphocutaneous infection.

Mycobacterium marinum is a nontuberculous mycobacteria with worldwide distribution that lives in fresh or salt water and is responsible for infections in fish, and sometimes in humans. Human disease consists mainly of cutaneous nodules, but deep structure involvement may also occur. Diagnosis of M. marinum infection remains a challenge, with a considerable time delay between onset of symptoms and diagnosis. We present a 33-year-old man with no immunosuppressive history who was seen in our department with skin nodules over his hand and forearm, distributed in a sporotrichoid pattern. His hobbies included maintaining an aquarium of tropical fish. Histological examination of the patient's skin biopsy was compatible with the diagnosis of mycobacterial infection, and the Ziehl-Neelsen staining revealed acid-fast bacilli. Molecular techniques confirmed the suspicion of M. marinum infection. A necropsy was performed on one of the patient's fish, more specifically, a Poecilia reticulata, and resulted in identification of M. marinum from its gut. The patient was treated with clarithromycin, ethambutol, and rifampicin for 9 months, with clearance of infection.

Antipsychotic plasma levels in the assessment of poor treatment response in schizophrenia.

OBJECTIVE: Treatment resistance is a challenge for the management of schizophrenia. It is not always clear whether inadequate response is secondary to medication ineffectiveness, as opposed to medication underexposure due to non-adherence or pharmacokinetic factors. We investigated the prevalence of subtherapeutic antipsychotic plasma levels in patients identified as treatment-resistant by their treating clinician. METHOD: Between January 2012 and April 2017, antipsychotic plasma levels were measured in 99 individuals provisionally diagnosed with treatment-resistant schizophrenia by their treating clinicians, but not prescribed clozapine. Patients were followed up to determine whether they were subsequently admitted to hospital. RESULTS: Thirty-five per cent of plasma levels were subtherapeutic, and of these, 34% were undetectable. Black ethnicity (P = 0.006) and lower dose (P < 0.001) were significantly associated with subtherapeutic/undetectable plasma levels. Individuals with subtherapeutic/undetectable levels were significantly more likely to be admitted to hospital (P = 0.02). CONCLUSION: A significant proportion of patients considered treatment-resistant have subtherapeutic antipsychotic plasma levels, and this is associated with subsequent admission. The presence of subtherapeutic plasma levels may suggest a need to address adherence or pharmacokinetic factors as opposed to commencing clozapine treatment. While antipsychotic levels are not recommended for the routine adjustment of dosing, they may assist with the assessment of potential treatment resistance in schizophrenia.