'Black Out Rage Gallon' (aka borg): An investigation of a risky drinking trend on TikTok.

ISSUE ADDRESSED: A 'Black Out Rage Gallon' (borg) is a customised, individual alcoholic beverage popularised on TikTok, whereby half the water in a gallon jug is replaced with alcohol (usually spirits), flavourings, electrolytes and caffeine. We investigated the characteristics and portrayal of the emerging alcohol trend associated with the hashtag descriptor #borg on TikTok. METHODS: We identified highly viewed TikTok videos with the #borg hashtag (n = 103) and conducted a content analysis, capturing viewer engagement ('likes', shares, comments), techniques used, characteristics of featured individuals, and the portrayal of alcohol and risky drinking behaviours. RESULTS: Alcohol was visible in three quarters of the videos analysed (n = 78, average amount of alcohol present 865 mL per borg) and consumed in one third of the videos (n = 34). One quarter of videos (n = 25) promoted alleged benefits of borg consumption compared to other alcohol products or approaches to drinking, yet only nine videos included a warning about potential harms. CONCLUSIONS: The borg trend on TikTok may encourage risky drinking, by portraying it in a style that younger viewers are likely to see as fun and entertaining. SO WHAT?: We were able to gain a better understanding of how this potentially health harming activity is represented on a social media platform that is popular with young people. The speedy dissemination of this trend highlights the need to monitor, investigate and counter emerging trends. Concurrently, there is an urgent need for content restrictions to limit the visibility and promotion of risky alcohol consumption on TikTok.

COVID-19 Vaccination in Young People with Functional Neurological Disorder: A Case-Control Study.

BACKGROUND: The emergence of acute-onset functional neurological symptoms, the focus of this study, is one of three stress responses related to immunisation. This case-control study documents the experience of 61 young people with past or current functional neurological disorder (FND) in relation to the COVID-19 vaccination program in Australia. METHODS: Information about the young person's/parent's choice and response pertaining to COVID-19 vaccination was collected as part of routine clinical care or FND research program follow-up. RESULTS: 61 young people treated for FND (47 females, mean age = 16.22 years) and 46 healthy controls (34 females, mean age = 16.37 years) were included in the study. Vaccination rates were high: 58/61 (95.1%) in the FND group and 45/46 (97.8%) in the control group. In the FND group, 2 young people (2/61, 3.3%) presented with new-onset FND following COVID-19 vaccination; two young people with resolved FND reported an FND relapse (2/36, 5.56%); and two young people with unresolved FND (2/20, 10.0%) reported an FND exacerbation. In the control group no FND symptoms were reported. CONCLUSIONS: Acute-onset FND symptoms following COVID-19 vaccination are uncommon in the general population. In young people prone to FND, COVID-19 vaccination can sometimes trigger new-onset FND, FND relapse, or FND exacerbation.

Screening and risk reducing surgery for endometrial or ovarian cancers in Lynch syndrome: a systematic review.

OBJECTIVE: Lynch syndrome is a hereditary cancer syndrome caused by mismatch repair gene mutations, and female carriers are at an increased risk of endometrial and ovarian cancer. The best approach to screening is not yet clear and practice varies across countries and centers. We aimed to provide evidence to inform the best approach to screening and risk reduction. METHODS: A systematic search of the literature was conducted (Medline, Embase, PubMed). Studies evaluating the following were included: women with Lynch syndrome (by mismatch repair mutation or Amsterdam II criteria), screening methods for endometrial and/or ovarian cancer, intervention included endometrial biopsy, transvaginal ultrasound, or serum cancer antigen 125 (CA-125), outcomes evaluated were number of cancers and/or endometrial hyperplasia. RESULTS: A total of 18 studies of Lynch syndrome carriers which screened for endometrial cancer using transvaginal ultrasound and/or hysteroscopy/endometrial biopsy revealed an incidence of 3.9% at the time of screening. Most (64.1%) endometrial cancers detected were from screening, with the balance detected in symptomatic women at the first screening visits, regular review, or between screening intervals. In mismatch repair carriers, the overall sensitivity of endometrial screening was 66.7%, and the number needed to screen ranged between 4 and 38 (median 7). The sensitivity of endometrial biopsy was 57.1% and the number needed to screen was 23-380 (median 78). The sensitivity of transvaginal ultrasound was 34.4% and the number needed to screen was 35-973 (median 170). Fourteen studies which screened for ovarian cancer using transvaginal ultrasound and/or CA-125 revealed an incidence of 1.3% at the time of screening and 42.9% of ovarian cancers were detected at asymptomatic screening. The sensitivity of ovarian screening was 54.6%, and the number needed to screen was 9-191 (median 23) in mismatch repair carriers. Thirteen studies reported 5.8% incident endometrial cancers and 0.5% ovarian cancers at time of risk reducing surgery. CONCLUSIONS: There is limited evidence to support screening for endometrial and ovarian cancer in Lynch syndrome and data on mortality reduction are not available. Further prospective, randomized trials comparing targeted screening methods are needed. Risk reducing surgery remains the most reliable way to reduce endometrial and ovarian cancer risk in Lynch syndrome.

(+)-Catharanthine potentiates the GABAA receptor by binding to a transmembrane site at the ß(+)/α(-) interface near the TM2-TM3 loop.

(+)-Catharanthine, a coronaridine congener, potentiates the γ-aminobutyric acid type A receptor (GABAAR) and induces sedation through a non-benzodiazepine mechanism, but the specific site of action and intrinsic mechanism have not beendefined. Here, we describe GABAAR subtype selectivity and location of the putative binding site for (+)-catharanthine using electrophysiological, site-directed mutagenesis, functional competition, and molecular docking experiments. Electrophysiological and in silico experiments showed that (+)-catharanthine potentiates the responses to low, subsaturating GABA at ß2/3-containing GABAARs 2.4-3.5 times more efficaciously than at ß1-containing GABAARs. The activity of (+)-catharanthine is reduced by the ß2(N265S) mutation that decreases GABAAR potentiation by loreclezole, but not by the ß3(M286C) or α1(Q241L) mutations that reduce receptor potentiation by R(+)-etomidate or neurosteroids, respectively. Competitive functional experiments indicated that the binding site for (+)-catharanthine overlaps that for loreclezole, but not those for R(+)-etomidate or potentiating neurosteroids. Molecular docking experiments suggested that (+)-catharanthine binds at the ß(+)/α(-) intersubunit interface near the TM2-TM3 loop, where it forms H-bonds with ß2-D282 (TM3), ß2-K279 (TM2-TM3 loop), and ß2-N265 and ß2-R269 (TM2). Site-directed mutagenesis experiments supported the in silico results, demonstrating that the K279A and D282A substitutions, that lead to a loss of H-bonding ability of the mutated residue, and the N265S mutation, impair the gating efficacy of (+)-catharanthine. We infer that (+)-catharanthine potentiates the GABAAR through several H-bond interactions with a binding site located in the ß(+)/α(-) interface in the transmembrane domain, near the TM2-TM3 loop, where it overlaps with loreclezole binding site.

Linking meta-omics to the kinetics of denitrification intermediates reveals pH-dependent causes of N2O emissions and nitrite accumulation in soil.

Soil pH is a key controller of denitrification. We analysed the metagenomics/transcriptomics and phenomics of two soils from a long-term liming experiment, SoilN (pH 6.8) and un-limed SoilA (pH 3.8). SoilA had severely delayed N2O reduction despite early transcription of nosZ (mainly clade I), encoding N2O reductase, by diverse denitrifiers. This shows that post-transcriptionally hampered maturation of the NosZ apo-protein at low pH is a generic phenomenon. Identification of transcript reads of several accessory genes in the nos cluster indicated that enzymes for NosZ maturation were present across a range of organisms, eliminating their absence as an explanation for the failure to produce a functional enzyme. nir transcript abundances (for NO2- reductase) in SoilA suggest that low NO2- concentrations in acidic soils, often ascribed to abiotic degradation, are primarily due to biological activity. The accumulation of NO2- in neutral soil was ascribed to high nar expression (nitrate reductase). The -omics results revealed dominance of nirK over nirS in both soils while qPCR showed the opposite, demonstrating that standard primer pairs only capture a fraction of the nirK pool. qnor encoding NO reductase was strongly expressed in SoilA, implying an important role in controlling NO. Production of HONO, for which some studies claim higher, others lower, emissions from NO2- accumulating soil, was estimated to be ten times higher from SoilA than from SoilN. The study extends our understanding of denitrification-driven gas emissions and the diversity of bacteria involved and demonstrates that gene and transcript quantifications cannot always reliably predict community phenotypes.

Effectiveness of technology-based educational interventions on the empowerment related outcomes of children and young adults with cancer: A quantitative systematic review.

AIM: To determine the effectiveness of technological-based educational interventions on the empowerment-related outcomes of children and young adults with cancer. DESIGN: Quantitative systematic review. DATA SOURCES: Six electronic databases, including PubMed, Cochrane Library, EMBASE, CINAHL, Scopus, and PsycINFO, were searched to identify eligible randomized controlled trials from each database's point of inception to December 2017. Grey literature was also searched from ProQuest and MedNar. REVIEW METHODS: A narrative summary of the results was undertaken owing to the small number of eligible studies and high heterogeneity across the studies. RESULTS: Five studies were included in the review. Five empowerment-related outcomes under the domain "patient states" were identified at differing time points of 3-month postintervention, immediate postintervention, and during treatment: (a) self-efficacy; (b) cancer knowledge; (c) health locus of control; (d) emotional well-being; and (e) quality of life. At 3-month postintervention, health locus of control was found to be significant in two studies and self-efficacy and cancer knowledge were found to be significant in one study. No difference in quality of life was found. At immediate postintervention, a beneficial indication was observed. During treatment, no statistical significance was found regarding the effectiveness of a technological-based cognitive behavioural package. CONCLUSION: Weak evidences led to inconclusive findings on the effectiveness of technological-based educational interventions on the empowerment-related outcomes of children and young adults with cancer. Future research will benefit from well-designed clinical trials that use a common outcome measurement to provide more information regarding the effectiveness of such interventions.

Corrigendum: Hepatic S6K1 Partially Regulates Lifespan of Mice with Mitochondrial Complex I Deficiency.

[This corrects the article on p. 113 in vol. 8, PMID: 28919908.].

Hepatic S6K1 Partially Regulates Lifespan of Mice with Mitochondrial Complex I Deficiency.

The inactivation of ribosomal protein S6 kinase 1 (S6K1) recapitulates aspects of caloric restriction and mTORC1 inhibition to achieve prolonged longevity in invertebrate and mouse models. In addition to delaying normative aging, inhibition of mTORC1 extends the shortened lifespan of yeast, fly, and mouse models with severe mitochondrial disease. Here we tested whether disruption of S6K1 can recapitulate the beneficial effects of mTORC1 inhibition in the Ndufs4 knockout (NKO) mouse model of Leigh Syndrome caused by Complex I deficiency. These NKO mice develop profound neurodegeneration resulting in brain lesions and death around 50-60 days of age. Our results show that liver-specific, as well as whole body, S6K1 deletion modestly prolongs survival and delays onset of neurological symptoms in NKO mice. In contrast, we observed no survival benefit in NKO mice specifically disrupted for S6K1 in neurons or adipocytes. Body weight was reduced in WT mice upon disruption of S6K1 in adipocytes or whole body, but not altered when S6K1 was disrupted only in neurons or liver. Taken together, these data indicate that decreased S6K1 activity in liver is sufficient to delay the neurological and survival defects caused by deficiency of Complex I and suggest that mTOR signaling can modulate mitochondrial disease and metabolism via cell non-autonomous mechanisms.

Transparent DNA/RNA Co-extraction Workflow Protocol Suitable for Inhibitor-Rich Environmental Samples That Focuses on Complete DNA Removal for Transcriptomic Analyses.

Adequate comparisons of DNA and cDNA libraries from complex environments require methods for co-extraction of DNA and RNA due to the inherent heterogeneity of such samples, or risk bias caused by variations in lysis and extraction efficiencies. Still, there are few methods and kits allowing simultaneous extraction of DNA and RNA from the same sample, and the existing ones generally require optimization. The proprietary nature of kit components, however, makes modifications of individual steps in the manufacturer's recommended procedure difficult. Surprisingly, enzymatic treatments are often performed before purification procedures are complete, which we have identified here as a major problem when seeking efficient genomic DNA removal from RNA extracts. Here, we tested several DNA/RNA co-extraction commercial kits on inhibitor-rich soils, and compared them to a commonly used phenol-chloroform co-extraction method. Since none of the kits/methods co-extracted high-quality nucleic acid material, we optimized the extraction workflow by introducing small but important improvements. In particular, we illustrate the need for extensive purification prior to all enzymatic procedures, with special focus on the DNase digestion step in RNA extraction. These adjustments led to the removal of enzymatic inhibition in RNA extracts and made it possible to reduce genomic DNA to below detectable levels as determined by quantitative PCR. Notably, we confirmed that DNase digestion may not be uniform in replicate extraction reactions, thus the analysis of "representative samples" is insufficient. The modular nature of our workflow protocol allows optimization of individual steps. It also increases focus on additional purification procedures prior to enzymatic processes, in particular DNases, yielding genomic DNA-free RNA extracts suitable for metatranscriptomic analysis.

Combination of ciclopirox olamine and sphingosine-1-phosphate as granulation enhancer in diabetic wounds.

Granulation tissue formation requires a robust angiogenic response. As granulation tissue develops, collagen fibers are deposited and compacted. Forces generated in the wake of this process drive wound contraction to reduce the wound area. In diabetics, both angiogenesis and wound contraction are diminished leading to impaired wound healing. To emulate this pathology and to address it pharmacologically, we developed a wound healing model in the diabetic Zucker fatty rat and tested a topical proangiogenic strategy combining antifungal agent ciclopirox olamine (CPX) and lysophospholipid sphingosine-1-phosphate (S1P) to promote diabetic wound closure. In vitro, we demonstrated that CPX + S1P up-regulates a crucial driver of angiogenesis, hypoxia-inducible factor-1, in endothelial cells. Injection of CPX + S1P into subcutaneously implanted sponges in experimental rats showed, in an additive manner, a fivefold increased endothelial infiltration and lectin-perfused vessel length. We developed a splinted diabetic rodent model to achieve low wound contraction rates that are characteristic for the healing mode of diabetic ulcers in humans. We discovered specific dorsal sites that allowed for incremental full-thickness excisional wound depths from 1 mm (superficial) to 3 mm (deep). This enabled us to bring down wound contraction from 51% in superficial wounds to 8% in deep wounds. While the effects of topical gel treatment of CPX + S1P were masked by the rodent-characteristic dominant contraction in superficial wounds, they became clearly evident in deep diabetic wounds. Here, a fivefold increase of functional large vessels resulted in accelerated granulation tissue formulation, accompanied by a 40% increase of compacted thick collagen fibers. This was associated with substantially reduced matrix metalloproteinase-3 and -13 expression. These findings translated into a fivefold increase in granulation-driven contraction, promoting diabetic wound closure. With CPX and S1P analogues already in clinical use, their combination presents itself as an attractive proangiogenic treatment to be repurposed for diabetic wound healing.

Simultaneous Delivery of Highly Diverse Bioactive Compounds from Blend Electrospun Fibers for Skin Wound Healing.

Blend emulsion electrospinning is widely perceived to destroy the bioactivity of proteins, and a blend emulsion of water-soluble and nonsoluble molecules is believed to be thermodynamically unstable to electrospin smoothly. Here we demonstrate a method to retain the bioactivity of disparate fragile biomolecules when electrospun. Using bovine serum albumin as a carrier protein; water-soluble vitamin C, fat soluble vitamin D3, steroid hormone hydrocortisone, peptide hormone insulin, thyroid hormone triiodothyronine (T3), and peptide epidermal growth factor (EGF) were simultaneously blend-spun into PLGA-collagen nanofibers. Upon release, vitamin C maintained the ability to facilitate Type I collagen secretion by fibroblasts, EGF stimulated skin fibroblast proliferation, and insulin potentiated adipogenic differentiation. Transgenic cell reporter assays confirmed the bioactivity of vitamin D3, T3, and hydrocortisone. These factors concertedly increased keratinocyte and fibroblast proliferation while maintaining keratinocyte basal state. This method presents an elegant solution to simultaneously deliver disparate bioactive biomolecules for wound healing applications.

Novel use for polyvinylpyrrolidone as a macromolecular crowder for enhanced extracellular matrix deposition and cell proliferation.

Macromolecular crowding (MMC) is a biophysical effect that governs biochemical processes inside and outside of cells. Since standard cell culture media lack this effect, the physiological performance of differentiated and progenitor cells, including extracellular matrix (ECM) deposition, is impaired in vitro. To bring back physiological crowdedness to in vitro systems, we have previously introduced carbohydrate-based macromolecules to culture media and have achieved marked improvements with mixed MMC in terms of ECM deposition and differentiation of mesenchymal stem cells (MSCs). We show here that although this system is successful, it is limited, due to viscosity, to only 33% of the fractional volume occupancy (FVO) of full serum, which we calculated to have an FVO of approximately 54% v/v. We show here that full-serum FVO can be achieved using polyvinylpyrrolidone (PVP) 360 kDa. Under these conditions, ECM deposition in human fibroblasts and MSCs is on par, if not stronger than, with original MMC protocols using carbohydrates, but with a viscosity that is not significantly changed. In addition, we have found that the proliferation rate for bone marrow-derived MSCs and fibroblasts increases slightly in the presence of PVP360, similar to that observed with carbohydrate-based crowders. A palette of MMC compounds is now emerging that enables us to tune the crowdedness of culture media seamlessly from interstitial fluid (9% FVO), in which the majority of tissue cells might be based, to serum environments mimicking intravascular conditions. Despite identical FVO's, individual crowder size effects play a role and different cell types appear to have preferences in terms of FVO and the crowder that this is achieved with. However, in the quest of crowders that we have predicted to have a smoother regulatory approval path, PVP is a highly interesting compound, as it has been widely used in the medical and food industries and shows a novel promising use in cell culture and tissue engineering.

Continual production of glycerol from carbon dioxide by Dunaliella tertiolecta.

Microalgae have high photosynthetic efficiencies and produce many valuable compounds from carbon dioxide. The Dunaliella genus accumulates glycerol, yet no commercial process currently exists for glycerol production from this microalga. Here it was found that in addition to intracellular accumulation, Dunaliella tertiolecta also releases glycerol into the external medium continuously, forming a large and stable carbon pool. The process is not affected by nutrient starvation or onset of cell death. Carbon dioxide was fixed at a constant rate, the bulk of it being channelled to extracellular glycerol (82%), resulting in enhanced photosynthetic carbon assimilation of 5 times that used for biomass production. The final extracellular glycerol concentration was 34 times the maximum concentration of intracellular glycerol; the latter declined further during cell death. Findings from this work will assist in the development of a bioconversion process to produce glycerol using D. tertiolecta without the need for cell harvest or disruption.

Microbiological and meteorological analysis of two Australian dust storms in April 2009.

Dust is an important source of bioaerosols including bacteria. In this study, the microbiology and meteorology of specific dust storms in Australia were investigated. The samples were collected from two dust events in April 2009 that were characterised by intense cold fronts that entrained dust from the highly erodible and drought-stricken Mallee and Riverina regions of Victoria and central NSW. In the first storm, the dust travelled eastward over Canberra and Sydney, and in the second storm, the dust travelled east/southeastward over Canberra and Melbourne. Rain fell on both cities during the second dust storm. Dust and rain samples were collected, cultured, and the composition compared using polymerase chain reaction denaturing gradient gel electrophoresis (PCR-DGGE). Multiple bands were evident on DGGE indicative of a diverse microflora, and identification of several bands confirmed the presence of multiple genera and species representing three phyla. Numerous bands represented Bacillus species, and these were present in multiple dust samples collected from both Canberra and Melbourne. Interestingly, the microflora present in rain samples collected in Canberra during the second dust storm was quite different and the DGGE banding patterns from these samples clustered separately to most dust samples collected at the same time. Identification of several DGGE bands and PCR products from these rain samples indicated the presence of Pseudomonas species. These results indicate that Australian dust and rain have a diverse microflora and highlights the contribution of dust events to the distribution of microbes in the environment.

Early detection of biomolecular changes in disrupted porcine cartilage using polarized Raman spectroscopy.

We evaluate the feasibility of applying polarized Raman spectroscopy in probing the early biochemical compositions and orientation changes in impacted porcine cartilage explants. We divide 100 fresh tibial cartilage explants into four groups: control (unimpacted) and 3 groups of single impact at 15, 20, and 25 MPa. Each group is examined for biochemical changes using Raman microscopy, cell viability changes using confocal fluorescence microscopy, and histological changes using the modified Mankin score. For the 15-MPa impact group, the modified Mankin score (p>0.05, n=15) and cell viability test (p>0.05, n=5) reveal no significant changes when compared to the control, but polarized Raman spectroscopy detects significant biochemical changes. A significant decrease in the parallel polarized intensity of the pyranose ring band at 1126 cm(-1) suggests a possible decrease in the glycoaminoglycan content in early cartilage damage (one-way analysis of variance with a post hoc Bonferonni test, p<0.05, n=10). For impacts greater than 15 MPa, cell viability and modified Mankin score are consistent with the changes in the observed polarized Raman signals. This suggests that the polarized Raman spectroscopy technique has potential for diagnosis and detection of early cartilage damage at the molecular level.

Creating new career pathways to reduce poverty, illiteracy and health risks, while transforming and empowering Cambodian women's lives.

Community health psychology provides a framework for local citizens themselves to systematically affect change in health and social inequalities, particularly through Participatory Action Research (PAR). The Cambodian NGO SiRCHESI launched a 24-month Hotel Apprenticeship Program (HAP) in 2006 to provide literacy, English, social skills, health education, hotel skills-training, work experience and a living wage to women formerly selling beer in restaurants; there they had faced workplace risks including HIV/AIDS, alcohol overuse, violence and sexual coercion. Quantitative and qualitative analyses indicate changes in health-related knowledge, behaviour, self-image and empowerment, as HAP trainees were monitored and evaluated within their new career trajectories.