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Rare coding variants in ten genes confer substantial risk for schizophrenia

Nature. 2022 Apr 8. doi: 10.1038/s41586-022-04556-w. Online ahead of print.

ABSTRACT

Rare coding variation has historically provided the most direct connections between gene function and disease pathogenesis. By meta-analysing the whole exomes of 24,248 schizophrenia cases and 97,322 controls, we implicate ultra-rare coding variants (URVs) in 10 genes as conferring substantial risk for schizophrenia (odds ratios of 3-50, P < 2.14 × 10-6) and 32 genes at a false discovery rate of <5%. These genes have the greatest expression in central nervous system neurons and have diverse molecular functions that include the formation, structure and function of the synapse. The associations of the NMDA (N-methyl-D-aspartate) receptor subunit GRIN2A and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) receptor subunit GRIA3 provide support for dysfunction of the glutamatergic system as a mechanistic hypothesis in the pathogenesis of schizophrenia. We observe an overlap of rare variant risk among schizophrenia, autism spectrum disorders1, epilepsy and severe neurodevelopmental disorders2, although different mutation types are implicated in some shared genes. Most genes described here, however, are not implicated in neurodevelopment. We demonstrate that genes prioritized from common variant analyses of schizophrenia are enriched in rare variant risk3, suggesting that common and rare genetic risk factors converge at least partially on the same underlying pathogenic biological processes. Even after excluding significantly associated genes, schizophrenia cases still carry a substantial excess of URVs, which indicates that more risk genes await discovery using this approach.

PMID:35396579 | DOI:10.1038/s41586-022-04556-w

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Increasing early exposure to mother’s own milk in premature newborns

J Perinatol. 2022 Apr 8. doi: 10.1038/s41372-022-01376-8. Online ahead of print.

ABSTRACT

OBJECTIVE: Increase the proportion of ≤33 weeks newborns exposed to mother’s own milk (MOM) oral care by 12 h of age by 20% over 2 years to support a healthier microbiome.

STUDY DESIGN: We implemented interventions to support early expression of colostrum and reliable delivery of resultant MOM to premature newborns. Statistical process control charts were used to track progress and provide feedback to staff. Proportions of newborns exposed to MOM by 12 h were compared relative to baseline.

RESULTS: There were 46, 66, and 46 newborns in the baseline, implementation, and sustainability periods, respectively. The primary outcome improved from 48% to 61% in the implementation period (relative change 1.27, 95% CI 0.89, 1.81, p = 0.2), to 69% in sustainability period (relative to baseline 1.45, 95% CI 1.02, 2.08, p = 0.03).

CONCLUSION: An interdisciplinary team-based, multicycle, quality improvement intervention resulted in increased rates of early exposure to MOM.

PMID:35396577 | DOI:10.1038/s41372-022-01376-8

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SARS-CoV-2 Spike S1-specific IgG kinetic profiles following mRNA or vector-based vaccination in the general Dutch population show distinct kinetics

Sci Rep. 2022 Apr 8;12(1):5935. doi: 10.1038/s41598-022-10020-6.

ABSTRACT

mRNA- and vector-based vaccines are used at a large scale to prevent COVID-19. We compared Spike S1-specific (S1) IgG antibodies after vaccination with mRNA-based (Comirnaty, Spikevax) or vector-based (Janssen, Vaxzevria) vaccines, using samples from a Dutch nationwide cohort. In adults 18-64 years old (n = 2412), the median vaccination interval between the two doses was 77 days for Vaxzevria (interquartile range, IQR: 69-77), 35 days (28-35) for Comirnaty and 33 days (28-35) for Spikevax. mRNA vaccines induced faster inclines and higher S1 antibodies compared to vector-based vaccines. For all vaccines, one dose resulted in boosting of S1 antibodies in adults with a history of SARS-CoV-2 infection. For Comirnaty, two to four months following the second dose (n = 196), S1 antibodies in adults aged 18-64 years old (436 BAU/mL, IQR: 328-891) were less variable and median concentrations higher compared to those in persons ≥ 80 years old (366, 177-743), but differences were not statistically significant (p > 0.100). Nearly all participants seroconverted following COVID-19 vaccination, including the aging population. These data confirm results from controlled vaccine trials in a general population, including vulnerable groups.

PMID:35396570 | DOI:10.1038/s41598-022-10020-6

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Accuracy of the doses computed by the Eclipse treatment planning system near and inside metal elements

Sci Rep. 2022 Apr 8;12(1):5974. doi: 10.1038/s41598-022-10072-8.

ABSTRACT

Metal artefacts degrade clinical image quality which decreases the confidence of using computed tomography (CT) for the delineation of key structures for treatment planning and leads to dose errors in affected areas. In this work, we investigated accuracy of doses computed by the Eclipse treatment planning system near and inside metallic elements for two different computation algorithms. An impact of CT metal artefact reduction methods on the resulting calculated doses has also been assessed. A water phantom including Gafchromic film and metal inserts was irradiated (max dose 5 Gy) using a 6 MV photon beam. Three materials were tested: titanium, alloy 600, and tungsten. The phantom CT images were obtained with the pseudo-monoenergetic reconstruction (PMR) and the iterative metal artefact reduction (iMAR). Image sets were used for dose calculation using an Eclipse treatment planning station (TPS). Monte Carlo (MC) simulations were used to predict the true dose distribution in the phantom allowing for comparison with doses measured by film and calculated by TPS. Measured and simulated percentage depth doses (PDDs) were not statistically different (p > 0.618). Regional differences were observed at edges of metallic objects (max 8% difference). However, PDDs simulated with and without film were statistically different (p < 0.002). PDDs calculated by the Acuros XB algorithm based on the dose-to-medium approach best matched the MC reference regardless of the CT reconstruction methods and inserts used (p > 0.078). PDDs obtained using other algorithms significantly differ from the MC values (p < 0.011). The Acuros XB algorithm with a dose-to-medium approach provides reliable dose calculation in all metal regions when using the Varian system. The inability of the AAA algorithm to model backscatter dose significantly limits its clinical application in the presence of metal. No significant impact on the dose calculation was found for a range of metal artefact reduction strategies.

PMID:35396569 | DOI:10.1038/s41598-022-10072-8

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Health Anxiety, Health Perception, and Healthy Lifestyle Behavior Among Psychiatric Patients During the COVID-19 Pandemic

Prim Care Companion CNS Disord. 2022 Apr 5;24(2):21m03197. doi: 10.4088/PCC.21m03197.

ABSTRACT

Objective: To compare the health anxiety and healthy lifestyle behavior experienced by psychiatric patients due to the coronavirus disease 2019 (COVID-19) pandemic with that of a control group.

Methods: The study included 120 outpatients (aged 18-65 years) diagnosed with a psychiatric illness (DSM-5 criteria) who presented to a psychiatry outpatient clinic between June and August 2020. The control group included 120 healthy individuals with a similar age and sex distribution as the patient group. Data were collected with a questionnaire developed by the authors to determine the participants’ adherence to COVID-19 hygiene rules and associated behavioral norms. The Health Anxiety Scale-Short Form, Health Perception Scale, and Health-Promoting Lifestyle Profile were completed by all participants.

Results: The mean Health Anxiety Scale score was significantly lower in the patient group compared to the control group (P < .01). Health anxiety was high in 8% of the patients and 32% of the controls. Also, the mean Health-Promoting Lifestyle Profile score was statistically significantly lower in the patient group compared to the control group (P < .01). There was no significant difference between the groups based on health perception scores and adherence to hygiene rules.

Conclusions: As expected, the healthy lifestyle behavior of individuals without psychiatric illness was higher compared to those with mental disorders. However, health anxiety about COVID-19 was higher among healthy individuals compared to those with a psychiatric disorder. Thus, it could be suggested that individuals without a psychiatric illness prior to the pandemic could need psychiatric assistance after the pandemic.

PMID:35395150 | DOI:10.4088/PCC.21m03197

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Comparison of Clinical Results of Oral Tranexamic Acid and Platelet Rich Plasma Therapies in Melasma Treatment

Dermatol Ther. 2022 Apr 8:e15499. doi: 10.1111/dth.15499. Online ahead of print.

ABSTRACT

The pathogenesis of melasma is not fully understood yet and this often causes difficulties in treatment. In our study, we aimed to compare the clinical results of oral TA and PRP therapies in patients with melasma. The clinical results of 30 melasma patients treated with oral TA and 30 melasma patients treated with PRP over the age of 18 who applied to the İnönü University Turgut Özal Medical Center Dermatology and Venereal Diseases Outpatient Clinic between September 2017 and June 2019 were retrospectively evaluated. Both oral TA and PRP therapies provided statistically significant improvement in melasma patients. 75% improvement in the MASI score was statistically significantly higher in the oral TA group compared to the PRP group. Although oral TA and PRP are both successful in the treatment of melasma, it has been found in our study that oral TA gives better results. More studies are needed to support our study, which is the first study comparing oral TA and PRP therapies in the literature. This article is protected by copyright. All rights reserved.

PMID:35395121 | DOI:10.1111/dth.15499

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Best practices in metabarcoding of fungi: from experimental design to results

Mol Ecol. 2022 Apr 8. doi: 10.1111/mec.16460. Online ahead of print.

ABSTRACT

The development of high-throughput sequencing (HTS) technologies has greatly improved our capacity to identify fungi and unveil their ecological roles across a variety of ecosystems. Here we provide an overview of current best practices in metabarcoding analysis of fungal communities, from experimental design through molecular and computational analyses. By re-analysing published datasets, we demonstrate that operational taxonomic units (OTUs) outperform amplified sequence variants (ASVs) in recovering fungal diversity, a finding that is particularly evident for long markers. Additionally, analysis of the full-length ITS region allows more accurate taxonomic placement of fungi and other eukaryotes compared to the ITS2 subregion. Finally, we show that specific methods for compositional data analyses provide more reliable estimates of shifts in community structure. We conclude that metabarcoding analyses of fungi are especially promising for integrating fungi into the full microbiome and broader ecosystem functioning context, recovery of novel fungal lineages and ancient organisms as well as barcoding of old specimens including type material.

PMID:35395127 | DOI:10.1111/mec.16460

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The occurrence and consequences of violence against healthcare workers in Turkey: before and during the 
COVID-19 pandemic

Fam Pract. 2022 Apr 8:cmac024. doi: 10.1093/fampra/cmac024. Online ahead of print.

ABSTRACT

BACKGROUND: Before and throughout the COVID-19 pandemic, healthcare workers (HCWs) were victims of workplace violence (WPV). There are no reliable statistics on the occurrence and consequences of WPV against HCWs in Turkey throughout the pandemic period.

OBJECTIVE: We investigated the rates of WPV against HCWs in Turkey in the pre-pandemic and pandemic periods, variables associated with WPV, and the relationship between these variables and job satisfaction and burnout.

METHODS: A structured online questionnaire was disseminated through social media channels to HCWs in various healthcare settings. All the respondents also completed the Maslach Burnout Inventory (MBI) and Job Satisfaction Scale. Based on the data obtained, we determined the frequency, causes, and consequences of WPV against HCWs before and during the pandemic.

RESULTS: There were 701 completed questionnaires. 68.2% of participants were female, and 65.6% of them were doctors. The rate of WPV was 54.1% and 24.3% before and during the pandemic, respectively. Verbal abuse was the most common kind of WPV. Female HCWs were more likely to be physically assaulted than their male counterparts, especially those working in COVID-19 units. The majority of HCWs who were exposed to the violence at least once did not report WPV. HCWs exposed to WPV during the pandemic reported more emotional exhaustion and depersonalization and a lower perceived level of personal achievement.

CONCLUSION: HCWs were exposed to significant levels of violence both before and during the pandemic. Preventing WPV against HCWs and removing barriers to reporting abuse is crucial.

PMID:35395085 | DOI:10.1093/fampra/cmac024

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A meta-regression analysis to evaluate the influence of branched-chain amino acids in lactation diets on sow and litter growth performance

J Anim Sci. 2022 Apr 8:skac114. doi: 10.1093/jas/skac114. Online ahead of print.

ABSTRACT

The branched-chain amino acids (BCAA) Ile, Leu, and Val are three dietary essential amino acids for lactating sows; however, effects of dietary BCAA on sow and litter growth performance in the literature are equivocal. Thus, a meta-regression analysis was conducted to evaluate the effects of BCAA and their interactions in lactating sow diets to predict litter growth performance, sow bodyweight change, and sow feed intake. Thirty-four publications that represented 43 trials from 1997 to 2020 were used to develop a database that contained 167 observations. Diets for each trial were reformulated using NRC (2012) nutrient loading values in an Excel-based spreadsheet. Amino acids were expressed on a standardized ileal digestible (SID) basis. Regression model equations were developed with the MIXED procedure of SAS (Version 9.4, SAS Institute, Cary, NC) and utilized the inverse of reported squared SEM with the WEIGHT statement to account for heterogeneous errors across studies. Predictor variables were assessed with a step-wise manual forward selection for model inclusion. Additionally, statistically significant (P < 0.05) predictor variables were required to provide an improvement of at least 2 Bayesian information criterion units to be included in the final model. Significant predictor variables within three optimum equations developed for litter ADG included the count of weaned pigs per litter, NE, SID Lys, CP, sow ADFI, Val:Lys, Ile:Lys, and Leu:Val. For sow BW change, significant predictor variables within two developed models included litter size at 24 h, sow ADFI, Leu:Lys, and Ile+Val:Leu. The optimum equation for sow ADFI included Leu:Trp, SID Lys, NE, CP, and Leu:Lys as significant predictor variables. Overall, the prediction equations suggest that BCAA play an important role in litter growth, sow BW change, and feed intake during lactation; however, the influence of BCAA on these criteria is much smaller than that of other dietary components such as NE, SID Lys, sow ADFI, and CP.

PMID:35395081 | DOI:10.1093/jas/skac114

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Autoclaving time-related reduction in metabolizable energy of poultry meal is greater in growing pigs compared with broiler chickens

J Anim Sci. 2022 Apr 8:skac117. doi: 10.1093/jas/skac117. Online ahead of print.

ABSTRACT

The objective of this study was to determine the energy utilization responses of growing pigs and broiler chickens to poultry meal that was autoclaved at 134°C for 0 to 180 min. Poultry meal from the same batch was autoclaved at 134°C for 7 autoclaving times of 0, 30, 60, 90, 120, 150, or 180 min to generate 7 samples. Eight experimental diets consisting of a basal diet based on corn and soybean meal, and 7 test diets in which 15% of energy-contributing ingredients in the basal diet was replaced with each of the 7 poultry meal samples were used. In experiment 1, there were 64 barrows (initial body weight = 19.4 ± 1.0 kg) allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Each pig received experimental diet during 5 d of adaptation followed by 5 d of quantitative total, but separate, collection of urine and feces. In experiment 2, a total of 512 male broiler chickens at d 17 post hatching (initial body weight = 660 ± 80 g) in 8 replicate cages were allotted to 8 experimental diets in a randomized complete block design with body weight as a blocking factor. Excreta were collected from d 20 to 22 post hatching, and birds were euthanized by CO2 asphyxiation for ileal digesta collection. Data from experiments 1 and 2 were pooled together for statistical analysis as a 2 × 7 factorial treatment arrangement with the effect of species (pigs or broiler chickens) and autoclaving time of poultry meal (7 autoclaving times between 0 and 180 min). An interaction between species and linear effect of autoclaving time was observed (P < 0.05) in metabolizable energy (ME) of poultry meal. Specifically, linear decrease in ME values in poultry meal with increasing autoclaving time was greater (P < 0.05) in growing pigs (4,792 to 3,897 kcal/kg dry matter) compared with broiler chickens (3,591 to 3,306 kcal/kg dry matter). The ME value of unautoclaved poultry meal was greater (P < 0.01) for pigs than broiler chickens at 4,792 vs. 3,591 kcal/kg dry matter. Although decrease in ME values with autoclaving time of poultry meal was greater in growing pigs than in broiler chickens, the ME in autoclaved poultry meal fed to pigs was greater than ME in non-autoclaved poultry meal fed to broiler chickens. Furthermore, the ratio of cysteine to crude protein concentration is a potential indicator for estimating the ratio of ME to gross energy in poultry meal for growing pigs (r 2 = 0.81) and broiler chickens (r 2 = 0.84).

PMID:35395084 | DOI:10.1093/jas/skac117