Exposure of iPSC-derived human microglia to brain substrates enables the generation and manipulation of diverse transcriptional states in vitro.

Microglia, the macrophages of the brain parenchyma, are key players in neurodegenerative diseases such as Alzheimer's disease. These cells adopt distinct transcriptional subtypes known as states. Understanding state function, especially in human microglia, has been elusive owing to a lack of tools to model and manipulate these cells. Here, we developed a platform for modeling human microglia transcriptional states in vitro. We found that exposure of human stem-cell-differentiated microglia to synaptosomes, myelin debris, apoptotic neurons or synthetic amyloid-beta fibrils generated transcriptional diversity that mapped to gene signatures identified in human brain microglia, including disease-associated microglia, a state enriched in neurodegenerative diseases. Using a new lentiviral approach, we demonstrated that the transcription factor MITF drives a disease-associated transcriptional signature and a highly phagocytic state. Together, these tools enable the manipulation and functional interrogation of human microglial states in both homeostatic and disease-relevant contexts.

Mode of Action of Kanglemycin A, an Ansamycin Natural Product that Is Active against Rifampicin-Resistant Mycobacterium tuberculosis.

Antibiotic-resistant bacterial pathogens pose an urgent healthcare threat, prompting a demand for new medicines. We report the mode of action of the natural ansamycin antibiotic kanglemycin A (KglA). KglA binds bacterial RNA polymerase at the rifampicin-binding pocket but maintains potency against RNA polymerases containing rifampicin-resistant mutations. KglA has antibiotic activity against rifampicin-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis (MDR-M. tuberculosis). The X-ray crystal structures of KglA with the Escherichia coli RNA polymerase holoenzyme and Thermus thermophilus RNA polymerase-promoter complex reveal an altered-compared with rifampicin-conformation of KglA within the rifampicin-binding pocket. Unique deoxysugar and succinate ansa bridge substituents make additional contacts with a separate, hydrophobic pocket of RNA polymerase and preclude the formation of initial dinucleotides, respectively. Previous ansa-chain modifications in the rifamycin series have proven unsuccessful. Thus, KglA represents a key starting point for the development of a new class of ansa-chain derivatized ansamycins to tackle rifampicin resistance.

Gap junctions mediate discrete regulatory steps during fly spermatogenesis.

Gametogenesis requires coordinated signaling between germ cells and somatic cells. We previously showed that Gap junction (GJ)-mediated soma-germline communication is essential for fly spermatogenesis. Specifically, the GJ protein Innexin4/Zero population growth (Zpg) is necessary for somatic and germline stem cell maintenance and differentiation. It remains unknown how GJ-mediated signals regulate spermatogenesis or whether the function of these signals is restricted to the earliest stages of spermatogenesis. Here we carried out comprehensive structure/function analysis of Zpg using insights obtained from the protein structure of innexins to design mutations aimed at selectively perturbing different regulatory regions as well as the channel pore of Zpg. We identify the roles of various regulatory sites in Zpg in the assembly and maintenance of GJs at the plasma membrane. Moreover, mutations designed to selectively disrupt, based on size and charge, the passage of cargos through the Zpg channel pore, blocked different stages of spermatogenesis. Mutations were identified that progressed through early germline and soma development, but exhibited defects in entry to meiosis or sperm individualisation, resulting in reduced fertility or sterility. Our work shows that specific signals that pass through GJs regulate the transition between different stages of gametogenesis.

Real world study of sacituzumab govitecan in metastatic triple-negative breast cancer in the United Kingdom.

BACKGROUND: Treatment options for pre-treated patients with metastatic triple-negative breast cancer (mTNBC) remain limited. This is the first study to assess the real-world safety and efficacy of sacituzumab govitecan (SG) in the UK. METHODS: Data was retrospectively collected from 16 tertiary UK cancer centres. Pts had a diagnosis of mTNBC, received at least two prior lines of treatment (with at least one being in the metastatic setting) and received at least one dose of SG. RESULTS: 132 pts were included. Median age was 56 years (28-91). All patients were ECOG performance status (PS) 0-3 (PS0; 39, PS1; 76, PS2; 16, PS3;1). 75% (99/132) of pts had visceral metastases including 18% (24/132) of pts with CNS disease. Median PFS (mPFS) was 5.2 months (95% CI 4.5-6.6) with a median OS (mOS) of 8.7 months (95% CI 6.8-NA). The most common adverse events (AEs) were fatigue (all grade; 82%, G3/4; 14%), neutropenia (all grade; 55%, G3/4; 29%), diarrhoea (all grade; 58%, G3/4, 15%), and nausea (all grade; 38%, G3/4; 3%). SG dose reduction was required in 54% of pts. CONCLUSION: This study supports significant anti-tumour activity in heavily pre-treated pts with mTNBC. Toxicity data aligns with clinical trial experience.

Ile105Val polymorphism in the GSTP1 gene is associated with susceptibility to acute myeloid leukemia: an updated systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: Several genetic variations are associated with acute myeloid leukemia (AML) susceptibility, including the GSTP1 Ile105Val polymorphism. Even with the existing meta-analysis conducted on the topic, no consensus has been reached since none of the studies available performed in-depth data analysis. Hence, we performed an updated systematic review and meta-analysis in this paper to obtain more precise estimates. MATERIALS AND METHODS: We searched various databases and calculated the odds ratio (OR) and 95% confidence interval (CI) to examine whether the GSTP1 Ile105Val polymorphism is associated with AML susceptibility. Further statistical analysis was also done to obtain more accurate and reliable findings. RESULTS: A total of 15 studies are included in the systematic review, but only 9 were included in the meta-analysis due to the studies deviating from the Hardy-Weinberg equilibrium. The analysis showed significantly increased susceptibility to AML in the allelic, co-dominant, and recessive models. Furthermore, subgroup analysis noted increased AML susceptibility in the non-Asian population. Comparing the proportions of the genotypes and alleles showed a significantly higher proportion of the Val/Val genotype and Val allele in the non-Asian cohort. CONCLUSION: The GSTP1 Ile105Val polymorphism is significantly associated with AML susceptibility, especially among non-Asians. Further investigation should be performed to strengthen the current results.

Increased family psychosocial focus during children's developmental assessments: a study of parents' views.

BACKGROUND: Family psychosocial challenges during the early years of a child's life are associated with later mental and physical health problems for the child. An increased psychosocial focus on parents in routine child developmental assessments may therefore be justified. METHODS: Participants in this qualitative study included 11 mothers and one parental couple (mother and father) with children aged 9-23 months. Participants were recruited to Project Family Wellbeing through their general practice in Denmark. Twelve interviews were conducted, transcribed and analysed with a deductive approach. The topic guide drew on the core components of the Health Belief Model, which also served as a framework for the coding that was conducted using thematic analysis. RESULTS: Results are presented in four themes and 11 subthemes in total. Parents welcome discussion of their psychosocial circumstances during their child's developmental assessments. Clinicians' initiatives to address psychosocial challenges and alignment of parents' and clinicians' expectations may be required to allow this discussion. A flowing conversation, an open communication style and a trustful relationship facilitate psychosocial discussion. Barriers included short consultation time, concerns about how information was used and when parents found specific psychosocial aspects stigmatising or irrelevant to discuss. CONCLUSION: Enquiry about the family's psychosocial circumstances in routine developmental assessments is acceptable among parents. Alignment of clinical and parental expectations of developmental assessments could facilitate the process. Future research should examine the predictive validity of the various components of developmental assessments. TRIAL REGISTRATION: This is a qualitative study. The study participants are part of the cohort from Project Family Wellbeing (FamilieTrivsel). The project's trial registry number: NCT04129359. Registered October 16th 2019.

A robust evaluation of 49 high-dose-rate prostate brachytherapy treatment plans including all major uncertainties.

BACKGROUND: Uncertainties in radiotherapy cause deviation from the planned dose distribution and may result in delivering a treatment that fails to meet clinical objectives. The impact of uncertainties is unique to the patient anatomy and the needle locations in HDR prostate brachytherapy. Evaluating this impact during treatment planning is not common practice, relying on margins around the target or organs-at-risk to account for uncertainties. PURPOSE: A robust evaluation framework for HDR prostate brachytherapy treatment plans was evaluated on 49 patient plans, measuring the range of possible dosimetric outcomes to the patient due to 14 major uncertainties. METHODS: Patient plans were evaluated for their robustness to uncertainties by simulating probable uncertainty scenarios. Five-thousand probabilistic and 1943 worst-case scenarios per patient were simulated by changing the position and size of structures and length of dwell times from their nominal values. For each uncertainty scenario, the prostate D90 and maximum doses to the urethra, D0.01cc , and rectum, D0.1cc , were calculated. RESULTS: The D90 was an average 1.16 ± 0.51% (mean ± SD) below nominal values for the probabilistic scenarios; the D0.01cc metric was 2.24 ± 0.90% higher; and D0.1cc was greater by 0.48 ± 0.30%. The D0.01cc and D90 metrics were more sensitive to uncertainties than D0.1cc , with a median of 79.0% and 84.9% of probabilistic scenarios passing the constraints, compared to 96.5%. The median pass-rate for scenarios that passed all three metrics simultaneously was 63.4%. CONCLUSIONS: Assessing treatment plan robustness improves plan quality assurance, is achievable in less than 1-min, and identifies treatment plans with poor robustness, allowing re-optimization before delivery.

Chemopreventive effect of a milk whey by-product derived from Buffalo (Bubalus bubalis) in protecting from colorectal carcinogenesis.

BACKGROUND: Several studies show that natural foods are a source of compounds with anticancer properties that affect the gut microbiota and its metabolites. In the present study, we investigate the effect of a delactosed buffalo milk whey by-product (DMW) on colorectal carcinogenesis. METHODS: The effect of DMW on colorectal carcinoma (CRC) was investigated in the established mouse model of azoxymethane (AOM)-induced colon carcinoma, which closely resembles the human clinical condition of CRC. The effect of DMW on CRC immortalized cell lines was also evaluated to further identify the antineoplastic mechanism of action. RESULTS: Pretreatment of AOM-treated mice with DMW significantly (P < 0.05) reduced the percentage of mice bearing both aberrant crypt foci with more than four crypts (which are early precancerous lesions that progress to CRC) and tumors. In addition, DMW completely counteracted the effect of AOM on protein expression of caspase-9, cleaved caspase-3 and poly ADP-ribose polymerase in colonic tissue. Administration of DMW alone (i.e. without AOM) resulted in changes in the composition of the gut microbiota, leading to enrichment or depletion of genera associated with health and disease, respectively. DMW was also able to restore AOM-induced changes in specific genera of the gut microbiota. Specifically, DMW reduced the genera Atopobiaceae, Ruminococcus 1 and Lachnospiraceae XPB1014 and increased the genera Parabacteroides and Candidatus Saccharimonas, which were increased and reduced, respectively, by AOM. Blood levels of butyric acid and cancer diagnostic markers (5-methylcytidine and glycerophosphocholine), which were increased by AOM treatment, were reduced by DMW. Furthermore, DMW exerted cytotoxic effects on two human CRC cell lines (HCT116 and HT29) and these effects were associated with the induction of apoptotic signaling. CONCLUSIONS: Our results suggest that DMW exerts chemopreventive effects and restores the gut microbiota in AOM-induced CRC, and induces cytotoxic effect on CRC cells. DMW could be an important dietary supplement to support a healthy gut microbiota and reduce the prevalence of CRC in humans. Video Abstract.

COVID-19 bacteremic co-infection is a major risk factor for mortality, ICU admission, and mechanical ventilation.

BACKGROUND: Recent single-center reports have suggested that community-acquired bacteremic co-infection in the context of Coronavirus disease 2019 (COVID-19) may be an important driver of mortality; however, these reports have not been validated with a multicenter, demographically diverse, cohort study with data spanning the pandemic. METHODS: In this multicenter, retrospective cohort study, inpatient encounters were assessed for COVID-19 with community-acquired bacteremic co-infection using 48-h post-admission blood cultures and grouped by: (1) confirmed co-infection [recovery of bacterial pathogen], (2) suspected co-infection [negative culture with ≥ 2 antimicrobials administered], and (3) no evidence of co-infection [no culture]. The primary outcomes were in-hospital mortality, ICU admission, and mechanical ventilation. COVID-19 bacterial co-infection risk factors and impact on primary outcomes were determined using multivariate logistic regressions and expressed as adjusted odds ratios with 95% confidence intervals (Cohort, OR 95% CI, Wald test p value). RESULTS: The studied cohorts included 13,781 COVID-19 inpatient encounters from 2020 to 2022 in the University of Alabama at Birmingham (UAB, n = 4075) and Ochsner Louisiana State University Health-Shreveport (OLHS, n = 9706) cohorts with confirmed (2.5%), suspected (46%), or no community-acquired bacterial co-infection (51.5%) and a comparison cohort consisting of 99,170 inpatient encounters from 2010 to 2019 (UAB pre-COVID-19 pandemic cohort). Significantly increased likelihood of COVID-19 bacterial co-infection was observed in patients with elevated ≥ 15 neutrophil-to-lymphocyte ratio (UAB: 1.95 [1.21-3.07]; OLHS: 3.65 [2.66-5.05], p < 0.001 for both) within 48-h of hospital admission. Bacterial co-infection was found to confer the greatest increased risk for in-hospital mortality (UAB: 3.07 [2.42-5.46]; OLHS: 4.05 [2.29-6.97], p < 0.001 for both), ICU admission (UAB: 4.47 [2.87-7.09], OLHS: 2.65 [2.00-3.48], p < 0.001 for both), and mechanical ventilation (UAB: 3.84 [2.21-6.12]; OLHS: 2.75 [1.87-3.92], p < 0.001 for both) across both cohorts, as compared to other risk factors for severe disease. Observed mortality in COVID-19 bacterial co-infection (24%) dramatically exceeds the mortality rate associated with community-acquired bacteremia in pre-COVID-19 pandemic inpatients (5.9%) and was consistent across alpha, delta, and omicron SARS-CoV-2 variants. CONCLUSIONS: Elevated neutrophil-to-lymphocyte ratio is a prognostic indicator of COVID-19 bacterial co-infection within 48-h of admission. Community-acquired bacterial co-infection, as defined by blood culture-positive results, confers greater increased risk of in-hospital mortality, ICU admission, and mechanical ventilation than previously described risk factors (advanced age, select comorbidities, male sex) for COVID-19 mortality, and is independent of SARS-CoV-2 variant.

Genomic testing in high-grade serous ovarian cancer: current options and future development.

Understanding the genomic complexity of high-grade serous ovarian cancer is now essential in guiding patient management, particularly in the first-line setting. Our knowledge in this area has expanded rapidly in recent years, with biomarkers developing in parallel to agents designed to exploit cancer-associated genetic aberrations. In this review we will take stock of the current landscape of genetic testing and look towards the future with developments that aim to refine personalized treatment paradigms and track treatment resistance in real time.

Cannabidiol as a Harm Reduction Strategy for People Who Use Drugs: A Rapid Review.

OBJECTIVE: The drug poisoning crisis throughout North America necessitates novel harm reduction approaches. Emerging evidence suggests that cannabidiol (CBD) may have some utility as a harm reduction modality for those with problematic substance use. This rapid review aimed to synthesize available evidence on CBD as a potential harm reduction tool for people who use drugs while providing clinical and research insights. METHOD: A systematic search in EMBASE, MEDLINE, CENTRAL, and CINAHL was completed in July 2022. For inclusion, studies had to meet the following criteria: (1) drawn from an adult population of people who use drugs; (2) investigates CBD as an intervention for problematic substance use or harm reduction-related outcomes; (3) be published after the year 2000 and in English; and (4) be primary research or a review article. A narrative synthesis was used to group outcomes relevant to harm reduction and provide clinical and research insights. RESULTS: We screened 3,134 records, of which 27 studies (5 randomized trials) were included. The evidence remains limited, but available studies support the potential utility of CBD to reduce drug-induced craving and anxiety in opioid use disorder. There were low-quality studies suggesting that CBD may improve mood and general well-being of people who use drugs. Evidence suggests that CBD monotherapy may not be an adequate harm reduction strategy for problematic substance use but rather an adjunct to the standard of care. CONCLUSION: Low-quality evidence suggests that CBD may reduce drug cravings and other addiction-related symptoms and that CBD may have utility as an adjunct harm reduction strategy for people who use drugs. However, there is a significant need for more research that accurately reflects CBD dosing and administration regimens used in a real-world context.

A view from mindreading on fast-and-slow thinking.

De Neys's incisive critique of empirical and theoretical research on the exclusivity feature underscores the depth of the challenge of explaining the interplay of fast and slow processes. We argue that a closer look at research on mindreading reveals abundant evidence for the exclusivity feature - as well as methodological and theoretical perspectives that could inform research on fast and slow thinking.

Model-agnostic unsupervised detection of bots in a Likert-type questionnaire.

To detect bots in online survey data, there is a wealth of literature on statistical detection using only responses to Likert-type items. There are two traditions in the literature. One tradition requires labeled data, forgoing strong model assumptions. The other tradition requires a measurement model, forgoing collection of labeled data. In the present article, we consider the problem where neither requirement is available, for an inventory that has the same number of Likert-type categories for all items. We propose a bot detection algorithm that is both model-agnostic and unsupervised. Our proposed algorithm involves a permutation test with leave-one-out calculations of outlier statistics. For each respondent, it outputs a p value for the null hypothesis that the respondent is a bot. Such an algorithm offers nominal sensitivity calibration that is robust to the bot response distribution. In a simulation study, we found our proposed algorithm to improve upon naive alternatives in terms of 95% sensitivity calibration and, in many scenarios, in terms of classification accuracy.

Moisturizer therapy in prevention of atopic dermatitis and food allergy: To use or disuse?

OBJECTIVE: To critically appraise the evidence for the role of regular moisturizer application in early life to prevent atopic dermatitis (AD) and food allergy (FA). DATA SOURCES: Primary peer-reviewed literature. STUDY SELECTIONS: Original research articles based on systematic reviews, interventional studies, retrospective studies, case-control studies, and cohort studies related to the subject matter. RESULTS: There is good evidence to show that epicutaneous sensitization through a defective skin barrier is important in the development of AD and FA. This supports moisturizer use in prevention because some of them have been proven to restore skin barrier with clear benefits in AD, whereas there is some limited evidence that these products may reduce allergic sensitization. However, moisturizers have varied effects depending on ingredients and formulation, some of which are paradoxical, such as increasing transepidermal water loss and enhancing penetration of substances in the skin. These effects may be responsible for some of the conflicting outcomes of prevention studies, some of which suggest that moisturizers are not useful in prevention of AD and FA, whereas others show a positive trend. Interestingly, there is some suggestion that moisturizers may increase the risk for allergy development perhaps through these paradoxical effects. CONCLUSION: Although moisturizer use is beneficial in the management of AD, current evidence suggests that it may be ineffective in prevention of AD and FA. Further studies are needed to determine the effects of moisturization on allergic sensitization and inflammation and to investigate whether moisturizer type, frequency, duration, and age of application substantially affect the prevention and development of these allergies.

Effects of whole body vibration exercise combined with weighted vest in older adults: a randomized controlled trial.

BACKGROUND: To evaluate the training effects of whole body vibration (WBV) combined with weighted vest (WV) in older adults. METHODS: This randomized controlled trial study was conducted in healthy older adults living in the community. Fifty-one participants were randomly allocated into 3 groups: group 1 (n = 17), WBV alone, training on WBV at a frequency 30 Hz, amplitude 2 mm, 10 sets of 1 min squats, with 60 s rest, group 2 (n = 15), WV alone, squat exercise, 10 sets of 1 min, with 60 s rest, while WV loaded with 10% body weight and group 3 (n = 19), WBV + WV, combining WBV exercise with the addition of a WV. All groups completed training 3 times per week for 8 weeks. The outcomes were total muscle mass, muscle thickness, maximal isometric strength, single-leg-stance and timed-up-and-go evaluated at baseline and after training. RESULTS: As a result of training all groups improved their isometric muscle strength with little difference between groups. The single-leg-stance significantly improved only in WBV + WV group 25.1 ± 10.8 s (mean ± 95% CI, p < 0.01). The timed-up-and-go improved in all groups, but the improvement was significantly greater in the WBV + WV group (17.5 ± 6.9%) compared to the WV (8.5 ± 3.2%) and WBV groups (9.2 ± 5.4%, p = 0.043, 0.023 respectively). Rectus femoris muscle thickness and total muscle mass were significantly increased in all groups equally with little difference between groups. CONCLUSION: The combined WBV + WV had a greater effect on the single-leg-stance and the timed-up-and-go compared to WV or WBV alone. TRIAL REGISTRATION: TCTR20190306001. Thai Clinical Trials Registry ( www.thaiclinicaltrials.org ). Date of registration: 6 March 2019.

The Lebanese Regie state-owned tobacco monopoly: lessons to inform monopoly-focused endgame strategies.

BACKGROUND: Many countries have started pursuing tobacco 'endgame' goals of creating a 'tobacco-free' country by a certain date. Researchers have presented models to attain this goal, including shifting the supply of tobacco to a monopoly-oriented endgame model (MOEM), wherein a state-owned entity controls the supply and distribution of tobacco products. Although not designed to end tobacco use, the Regie in Lebanon exhibits some of the key features identified in MOEM and hence can serve as a practical example from which to draw lessons. METHODS: We comprehensively review previous literature exploring tobacco endgame proposals featuring a MOEM. We distil these propositions into core themes shared between them to guide a deductive analysis of the operations and actions of the Regie to investigate how it aligns (or does not) with the features of the MOEM. RESULTS: Analysing the endgame proposals featuring MOEM, we generated two main themes: the governance of the organisation; and its operational remit. In line with these themes, the investigation of the Regie led to several reflections on the endgame literature itself, including that it: (i) does not seem to fully appreciate the extent to which the MOEM could end up acting like Transnational Tobacco Companies (TTC); (ii) has only vaguely addressed the implications of political context; and (iii) does not address tobacco growing despite it being an important element of the supply chain. CONCLUSION: The implementation of tobacco endgame strategies of any type is now closer than ever. Using the Regie as a practical example allows us to effectively revisit both the potential and the pitfalls of endgame strategies aiming to introduce some form of monopoly and requires a focus on: (i) establishing appropriate governance structures for the organisation; and (ii) adjusting the financial incentives to supress any motivation for the organisation to expand its tobacco market.

Micrococcin P1 and P2 from Epibiotic Bacteria Associated with Isolates of Moorea producens from Kenya.

Epibiotic bacteria associated with the filamentous marine cyanobacterium Moorea producens were explored as a novel source of antibiotics and to establish whether they can produce cyclodepsipeptides on their own. Here, we report the isolation of micrococcin P1 (1) (C48H49N13O9S6; obs. m/z 1144.21930/572.60381) and micrococcin P2 (2) (C48H47N13O9S6; obs. m/z 1142.20446/571.60370) from a strain of Bacillus marisflavi isolated from M. producens' filaments. Interestingly, most bacteria isolated from M. producens' filaments were found to be human pathogens. Stalked diatoms on the filaments suggested a possible terrestrial origin of some epibionts. CuSO4·5H2O assisted differential genomic DNA isolation and phylogenetic analysis showed that a Kenyan strain of M. producens differed from L. majuscula strain CCAP 1446/4 and L. majuscula clones. Organic extracts of the epibiotic bacteria Pseudoalteromonas carrageenovora and Ochrobactrum anthropi did not produce cyclodepsipeptides. Further characterization of 24 Firmicutes strains from M. producens identified extracts of B. marisflavi as most active. Our results showed that the genetic basis for synthesizing micrococcin P1 (1), discovered in Bacillus cereus ATCC 14579, is species/strain-dependent and this reinforces the need for molecular identification of M. producens species worldwide and their epibionts. These findings indicate that M. producens-associated bacteria are an overlooked source of antimicrobial compounds.

Sugar-sweetened beverage consumption and overweight and obesity in adolescents in Ho Chi Minh City, Vietnam: a population-based analysis.

BACKGROUND: The aim of this research was to describe the patterns of consumption of multiple sugar-sweetened beverages (including modern and traditional ones) among adolescents in Ho Chi Minh City and to identify a possible relationship between this consumption and overweight, obesity, and other factors. METHODS: A secondary analysis from a cross-sectional study of 11-15-year-old students from 31 junior high schools across Ho Chi Minh City was used. We measured the students' anthropometric status and assessed beverage consumption using a validated Food Frequency Questionnaire. Multivariate logistic regression models were used to identify the association between the consumption of sugar-sweetened beverages, obesity and other factors. RESULTS: The sugar-sweetened beverages (SSB) ranged widely from modern soft drinks and powdered drinks to traditional sugar-added fruit and leaf juices, and milk-based drinks. These beverages were very popular among 2,660 participants with 36% consuming at least one variety daily. Factors positively associated with sugar-sweetened beverage consumption included a higher level of physical activity, higher consumption of fast foods, and daily fruit and vegetable consumption. We found a negative association between milk-based SSBs and the overweight and obesity status of the students, i.e. every kcal more of fresh milk with sugar and condensed milk can reduce an obesity odd of 0.005 (95% CI [0.002-0.008], p < 0.001) and 0.004 (95% CI [0.002-0.010], p = 0.044) consecutively. None of the other SSBs was significantly related to adolescent overweight and obesity. CONCLUSIONS: Milk-based drinks potentially protect adolescents against overweight and obesity. Further research to assess this protection is needed.

Outpatient palliative care during the COVID-19 pandemic: a retrospective single centre analysis in Germany.

BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has challenged health care systems worldwide. In Germany, patients in a palliative care setting have the opportunity to receive treatment by a specialised mobile outpatient palliative care team (OPC). The given retrospective single centre analysis describes the use of OPC structures for terminally ill COVID-19 patients during the height of the pandemic in Germany and aims to characterise this exceptional OPC patient collective. METHODS: First, death certificates were analysed in order to collect data about the place of death of all deceased COVID-19 patients (n = 471) within our local governance district. Second, we investigated whether advance care planning structures were established in local nursing homes (n = 30) during the height of the COVID-19 pandemic in 2020. Third, we examined patient characteristics of COVID-19 negative (n = 1579) and COVID-19 positive (n = 28) patients treated by our tertiary care centre guided OPC service. RESULTS: The analysis of death certificates in our local district revealed that only 2.1% of all deceased COVID-19 patients had succumbed at their home address (n = 10/471). In contrast, 34.0% of COVID-19 patients died in nursing homes (n = 160/471), whereas 63.5% died in an inpatient hospital setting (n = 299/471). A large proportion of these hospitalised patients died on non-intensive care unit wards (38.8%). Approximately 33.0% of surveyed nursing homes had a palliative care council service and 40.0% of them offered advance care planning (ACP) structures for their nursing home residents. In our two OPC collectives we observed significant differences concerning clinical characteristics such as the Index of Eastern Cooperative Oncology Group [ECOG] (p = 0.014), oncologic comorbidity (p = 0.004), as well as referrer and primary patient location (p = 0.001, p = 0.033). CONCLUSIONS: Most COVID-19 patients in our governance district died in an inpatient setting. However, the highest number of COVID-19 patients in our governance district who died in an outpatient setting passed away in nursing homes where palliative care structures should be further expanded. COVID-19 patients who died under the care of our OPC service had considerably fewer oncologic comorbidities. Finally, to relieve conventional health care structures, we propose the expansion of established OPC structures for treating terminally ill COVID-19 patients.

Profiling the tackle and its injury characteristics in premier New Zealand club rugby union players over a complete season.

OBJECTIVES: RugbySmart is a safe tackle technique education programme. Our objective was to identify whether the RugbySmart-recommended safe tackle technique was exhibited by club rugby players and whether tackle-related injuries showed poor tackle technique characteristics. METHODS: The prospective cohort design enabled 28 senior club based amateur male rugby union players from New Zealand to be followed over 18 matches in the 2017 rugby season. Game video analysis by three analysts provided categorisation of tackle technique into type, approach, foot contact, leading foot and rear foot position, face and head position. Injuries were diagnosed by the same sports medicine physician. RESULTS: In the 18 matches, 28 players completed a combined total of 3006 tackles, with only six tackle-related injuries sustained. Notable findings included: (1) forwards complete more tackles than backs; (2) shoulder tackles were the most prevalent tackle; (3) good tackle technique as promoted by RugbySmart was demonstrated in 57.9% of all tackles and (4) of the six tackle-related injuries, two occurred despite RugbySmart desired tackle techniques. CONCLUSION: This is the first study to investigate whether players were performing the recommended 'safe tackle technique' proposed by New Zealand Rugby's RugbySmart programme. As two of six tackle-related injuries occurred despite the RugbySmart preferred technique being performed, further technique analysis and a larger sample are needed to determine what techniques reduce risk of injury during tackles. As only 57.9% of tackles were performed with RugbySmart head and foot positions, further research and education regarding tackle technique recommendations are needed.