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Fermented foods are becoming more popular due to their purported links to metabolic health and the gut microbiome. However, direct clinical evidence for the health claims is lacking. Here, we describe an eight-week clinical trial that explored the effects of a four-week kombucha supplement in healthy individuals consuming a Western diet, randomized into the kombucha (n = 16) or control (n = 8) group. We collected longitudinal stool and blood samples to profile the human microbiome and inflammation markers. We did not observe significant changes in either biochemical parameters or levels of circulating markers of inflammation across the entire cohort. However, paired analysis between baseline and end of intervention time points within kombucha or control groups revealed increases in fasting insulin and in HOMA-IR in the kombucha group whereas reductions in HDL cholesterol were associated with the control group. Shotgun metagenomic analysis revealed the relative abundance of Weizmannia, a kombucha-enriched probiotic and several SCFA producing taxa to be overrepresented in consumers at the end of the intervention. Collectively, in our healthy cohort consuming a Western diet, a short-term kombucha intervention induced modest impacts on human gut microbiome composition and biochemical parameters, which may be attributed to relatively small number of participants and the extensive inter-participant variability.

CRISPR-Cas enzymes enable RNA-guided bacterial immunity and are widely used for biotechnological applications including genome editing. In particular, the Class 2 CRISPR-associated enzymes (Cas9, Cas12 and Cas13 families), have been deployed for numerous research, clinical and agricultural applications. However, the immense genetic and biochemical diversity of these proteins in the public domain poses a barrier for researchers seeking to leverage their activities. We present CasPEDIA (http://caspedia.org), the Cas Protein Effector Database of Information and Assessment, a curated encyclopedia that integrates enzymatic classification for hundreds of different Cas enzymes across 27 phylogenetic groups spanning the Cas9, Cas12 and Cas13 families, as well as evolutionarily related IscB and TnpB proteins. All enzymes in CasPEDIA were annotated with a standard workflow based on their primary nuclease activity, target requirements and guide-RNA design constraints. Our functional classification scheme, CasID, is described alongside current phylogenetic classification, allowing users to search related orthologs by enzymatic function and sequence similarity. CasPEDIA is a comprehensive data portal that summarizes and contextualizes enzymatic properties of widely used Cas enzymes, equipping users with valuable resources to foster biotechnological development. CasPEDIA complements phylogenetic Cas nomenclature and enables researchers to leverage the multi-faceted nucleic-acid targeting rules of diverse Class 2 Cas enzymes.

Dysregulated oxidative stress plays a major role in cancer pathogenesis and some types of cancer cells are particularly vulnerable to inhibition of their cellular antioxidant capacity. Glutamate-cysteine ligase (GCL) is the first and rate-limiting step in the synthesis of the major cellular antioxidant glutathione (GSH). Developing a GCL inhibitor may be an attractive therapeutic strategy for certain cancer types that are particularly sensitive to oxidative stress. In this study, we reveal a cysteine-reactive ligand, EN25, that covalently targets an allosteric cysteine C114 on GCLM, the modifier subunit of GCL, and leads to inhibition of GCL activity. This interaction also leads to reduced cellular GSH levels and impaired cell viability in ARID1A-deficient cancer cells, which are particularly vulnerable to glutathione depletion, but not in ARID1A-positive cancer cells. Our studies uncover a novel potential ligandable site within GCLM that can be targeted to inhibit GSH synthesis in vulnerable cancer cell types.

People are widely exposed to polycyclic aromatic hydrocarbons, like benzo[a]pyrene (BaP). Prior studies showed that prenatal exposure to BaP depletes germ cells in ovaries, causing earlier onset of ovarian senescence post-natally; developing testes were affected at higher doses than ovaries. Our primary objective was to determine if prenatal BaP exposure results in transgenerational effects on ovaries and testes. We orally dosed pregnant germ cell-specific EGFP-expressing mice (F0) with 0.033, 0.2, or 2 mg/kg-day BaP or vehicle from embryonic day (E) 6.5-11.5 (F1 offspring) or E6.5-15.5 (F2 and F3). Ovarian germ cells at E13.5 and follicle numbers at postnatal day 21 were significantly decreased in F3 females at all doses of BaP; testicular germ cell numbers were not affected. E13.5 germ cell RNA-sequencing revealed significantly increased expression of male-specific genes in female germ cells across generations and BaP doses. Next, we compared the ovarian effects of 2 mg/kg-day BaP dosing to wild type C57BL/6J F0 dams from E6.5-11.5 or E12.5-17.5. We observed no effects on F3 ovarian follicle numbers with either of the shorter dosing windows. Our results demonstrate that F0 BaP exposure from E6.5-15.5 decreased the number of and partially disrupted transcriptomic sexual identity of female germ cells transgenerationally.

Lanthanide borosilicate glasses containing Pu and the nonradioactive analog element Ce were subjects of an x-ray absorption spectroscopy investigation to quantify the +3/+4 ratio of these redox-sensitive elements. The data show that the dominant oxidation states are +4 for Pu and +3 for Ce. The data also indicate that the reductive potential of glasses can be quantified from a solution chemistry method adapted to glass chemistry, although allowances must be made for glass composition. These data can therefore be used to formulate glass compositions and processing schedules that lead to a controlled oxidation state of Pu in melts. Furthermore, the data show that Ce is a poor analog for Pu behavior in melts and that the suitability of surrogates can be assessed by the evaluation approach presented here. The method demonstrated in this paper can be used to estimate the oxidation states of a range of multi-valent elements as functions of temperature and composition with data from only a single redox couple.

Commercial, recreational, and indigenous fisheries are critical to coastal economies and communities in the United States. For over three decades, the federal government has formally recognized the impact of fishery disasters via federal declarations. Despite these impacts, national syntheses of the dynamics, impacts, and causes of fishery disasters are lacking. We developed a nationwide Federal Fishery Disaster database using National Oceanic and Atmospheric Administration (NOAA) fishery disaster declarations and fishery revenue data. From 1989-2020, there were 71 federally approved fishery disasters (eleven are pending), which spanned every federal fisheries management region and coastal state in the country. To date, we estimate fishery disasters resulted in $2B (2019 USD) in Congressional allocations, and an additional, conservative estimate of $3.2B (2019 USD) in direct revenue loss. Despite this scale of impact, the disaster assistance process is largely ad hoc and lacks sufficient detail to properly assess allocation fairness and benefit. Nonetheless, fishery disasters increased in frequency over time, and the causes of disasters included a broad range of anthropogenic and environmental factors, with a recent shift to disasters now almost exclusively caused by extreme environmental events (e.g., marine heatwaves, hurricanes, and harmful algal blooms). Nationwide, 84.5% of fishery disasters were either partially or entirely attributed to extreme environmental events. As climate change drives higher rates of such extreme events, and as natural disaster assistance requests reach an all-time high, the federal system for fisheries disaster declaration and mitigation must evolve in order to effectively protect both fisheries sustainability and societal benefit.

Sexual communication skills are needed to create healthy romantic relationships. Arguably, these skills also can be used to prevent some instances of unwanted sex. This study presents a qualitative analysis of adolescents' comments after reading a teen-friendly article on sexual consent as part of a web-based sexual health promotion intervention. The sample was comprised predominantly of female adolescents recruited from a Midwest urban region in the United States. Adolescents varied with respect to self-efficacy to request, provide, and deny consent, as well as the perceived need to ask for consent in the context of established relationships. Many adolescents perceived that nonverbal methods of communication were sufficient to request, provide, or deny sexual consent. Factors that make it difficult to discuss sexual boundaries and say "no" to unwanted sex included low self-efficacy and an underlying desire to nurture or preserve a relationship. Cultural norms must be changed to support verbal, affirmative sexual consent. In addition, adolescents must be aided in the development of skills to request sexual consent, say "yes" to specific activities, and say "no" to others. Without supportive norms and skills to enhance self-efficacy, adolescents may be unwilling to engage in verbal communication about sexual consent and boundaries.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

This music score was submitted for the Kaleidoscope 2020 Call for Scores, an open access collaboration with the UCLA Music Library.

The catastrophic devastation from recent natural calamities in the Philippines such as Typhoon Yolanda and Central Visayas earthquake in 2013 had made disaster preparedness a primary concern in the country. Prompted by the critical need to use science to save lives, this study developed Science of Survival (SOS) pamphlets titled "When the Wind Rages and Water Rises: A Science of Survival Pamphlet for Typhoon, Flashflood, Storm Surge and Tsunami" and "When the Earth Moves: A Science of Survival Pamphlet for Earthquakes and Their Aftermath (Liquefaction, Fire, Landslide and Tsunami)". The study used the developmental research design consisting of three phases: needs and context analysis phase, design, development and formative evaluation phase, and semi-summative evaluation phase. By carefully documenting the iterative process of analysis, design, evaluation and revision, insights were sought with regard to the development of pamphlets that provide useful and scientifically accurate information about surviving natural calamities such as typhoons and earthquakes. Experts from government agencies involved in disaster risk reduction and management, science experts in the university, and students who were victims of major disasters reviewed and evaluated the pamphlets. The results of the semi-summative quantitative evaluation showed that both pamphlets are highly acceptable as supplementary resource materials on disaster response and management.

Background Approximately 28% of children and adolescents undergoing major surgery develop chronic postsurgical pain (CPSP; pain persisting>3 months). A previous review attempted to investigate biopsychosocial prognostic factors for pediatric CPSP; however, due to lack of data, no meta-analytic techniques were employed. Since that review, numerous studies have investigated risk/protective factors that fall within an Interpersonal Fear Avoidance Model for CPSP, thus warranting a reinvestigation of prognostic factors. Objective This systematic review and meta-analysis aimed to examine prognostic factors, measurement tools applied, and their effect on the development of CPSP. Evidence review Prospective, observational studies examining prognostic factors of pediatric CPSP using validated self-report measures were included. 4884 unique publications were screened and 15 met inclusion criteria. Findings The pooled effect size for the association between presurgical child pain intensity and the presence of child CPSP was significant, OR=0.540 (95% CI=0.184 to 0.894). Child anxiety, child pain-related anxiety, and parent pain catastrophizing were not significant prognostic factors for child CPSP. Using Grading of Recommendations, Assessment, Development, and Evaluation, the certainty in prognostic estimates was moderate. Risk of bias using Quality in Prognostic Study tool ranged from low to moderate. Conclusions Presurgical pain was the only presurgical risk factor at the meta-analytic level that significantly predicted pediatric CPSP, highlighting the importance of prioritizing pain management throughout the perioperative experience, starting before surgery. Depressive symptoms and sleep disturbance were the two potential risk/protective factors that were unable to be assessed due to insufficient data or use of an unvalidated measure indicating a critical need for future research. [ABSTRACT FROM AUTHOR]

Background According to the prior 2017 review (Rabbitts et al), approximately 20% of children and adolescents develop chronic postsurgical pain (CPSP; ie, pain persisting >3 months after surgery) after major surgeries, which is associated with adverse functional and psychological consequences. A major barrier was that definitions of CPSP applied were highly variable. Since that prior review was conducted (n=4 studies in meta-analysis), numerous relevant studies have been published warranting an update. Objective The aims of this current review were to: (1) provide an updated prevalence estimate for pediatric CPSP and (2) examine definitions of pediatric CPSP applied in current research. Evidence review Prospective, observational studies examining CPSP using a validated self-report pain intensity measure in children were included. 4884 unique publications were screened with 20 articles meeting inclusion criteria. Risk of bias using Quality in Prognostic Study tool ranged from low to high. Findings The pooled prevalence of CPSP among mostly major surgeries was 28.2% (95% CI 21.4% to 36.1%). Subgroup analysis of spinal fusion surgeries identified a prevalence of 31% (95% CI 21.4% to 43.5%). Using Grading of Recommendations, Assessment, Development, and Evaluation, the certainty in prevalence estimates was moderate. Studies used a range of valid pain intensity measures to classify CPSP (eg, Numeric Rating Scale), often without pain interference or quality of life measures. Conclusions The overall prevalence of pediatric CPSP is higher than estimated in the prior review, and quality of studies generally improved though with some heterogeneity. Standardizing the measurement of CPSP will facilitate future efforts to combine and compare data across studies. [ABSTRACT FROM AUTHOR]

Vesicular stomatitis virus (VSV) outbreaks periodically occur in livestock in the western US and are thought to originate from outside this country. Feral swine (Sus scrofa) have been identified as an amplifying host for vesicular stomatitis New Jersey virus (VSNJV) and have been used to better understand the epidemiology of this virus through serosurveillance. This study aimed to determine if antibodies to vesicular stomatitis Indiana virus (VSIV) and VSNJV were present in feral swine in the western US and to determine if seropositive animals were associated with areas of previously detected VSV in livestock. A total of 4,541 feral swine samples was tested using virus neutralization (VN); samples exhibiting neutralizing activity against one or more of the viruses were confirmed using competitive ELISA (cELISA). Eight sera exhibited neutralizing activity by VN assay and a single serum sample from an animal from Kinney County, Texas sampled in December 2019 tested positive for antibodies to VSIV by cELISA. This finding is supported by a local outbreak of VSIV in horses in the same county in June 2019. The low prevalence of antibodies against VSNJV and VSIV was unexpected but indicates that feral swine in the western US do not represent an endemic reservoir for either of these viruses. [ABSTRACT FROM AUTHOR]

Wild pigs (Sus scrofa) are among the most detrimental invasive species in the USA. They are damaging to crops and agriculture, pose a public health risk as reservoirs of zoonotic pathogens, and may also spread disease to livestock. One pathogen identified in wild pigs is bovine viral diarrhea virus (BVDV), a virus that causes an economically important disease of cattle (Bos taurus and Bos indicus). We sought to determine the BVDV seroprevalence in wild pigs in 17 states across the US and to determine whether age category, sex, or location were associated with a positive antibody titer. Serum samples from 945 wild pigs were collected from 17 US states. Virus neutralization assays were performed to determine antibody titers against BVDV-1b and BVDV-2a. Total BVDV seroprevalence for the study area was 5.8% (95% confidence interval [CI], 4.11-8.89). Seroprevalence across all evaluated states was determined to be 4.4% (95% CI, 2.48-6.82) for BVDV-1b and 3.6% (95% CI, 1.54-5.60) for BVDV-2a. The seroprevalence for individual states varied from 0% to 16.7%. There was no statistical difference in median antibody titer for BVDV-1b or BVDV-2a by sex or age category. State seroprevalences for both BVDV-1b and BVDV-2a were associated with wild pig population estimates for those states. [ABSTRACT FROM AUTHOR]