Low-volume combined aerobic and resistance high-intensity interval training in type 2 diabetes: a randomised controlled trial.

Objective: The objective of this study was to compare the effects of novel, time-efficient, low-volume combined aerobic and resistance high-intensity interval training (C-HIIT), and current exercise guidelines (210 min/week of combined moderate-intensity continuous training (C-MICT)), with waitlist control (CON) on glycaemic control in people with type 2 diabetes mellitus (T2D). Methods: Sixty-nine low-active people with T2D were randomised to 8 weeks of supervised C-HIIT (78 min/week), supervised C-MICT (210 min/week), or waitlist CON. Those in waitlist CON were re-randomised to supervised C-HIIT/C-MICT at week 8. Following 8 weeks of supervised training, participants completed 10 months of self-directed exercise. Outcomes were assessed at baseline, week 8 and month 12. Participants in waitlist CON were only included in the exercise groups for the month 12 analysis. Analyses were completed using intention-to-treat analysis of covariance (n=69; week 8) and linear mixed modelling (n=63; month 12). Results: Compared with CON, at week 8, HbA1c decreased in C-HIIT (adjusted mean difference: -0.7% (95% CI -1.3, -0.2%)) and C-MICT (-1.2% (-1.9, -0.6%)). There were also improvements in C-HIIT and C-MICT versus CON at week 8 for fat mass (-1.9 (-3.1, -0.6) and -1.5 (-2.6, -0.4) kg, respectively), lean mass (1.5 (0.8, 2.3) and 0.9 (0.1, 1.7) kg), and exercise capacity (124 (77, 171) and 49 (5, 93) s). At month 12, adherence was low, and most measures returned to baseline. Conclusions: Low-volume C-HIIT (78 min/week) and C-MICT (210 min/week) improved glycaemic control, body composition and exercise capacity similarly over 8 weeks in people with T2D. However, at month 12, improvements were not maintained following self-directed exercise. Regardless, these data suggest that supervised low-volume C-HIIT is a time-efficient and effective strategy for improving outcomes in T2D.

Time to Develop Guidelines for Spiritual Care in Serious Illness.

In 2022, a JAMA systematic review of 342 high quality studies called for spiritual care to be a routine part of care for patients with serious illness. The review's multidisciplinary panel made several recommendations for addressing patients' and families' spiritual concerns. Despite these evidence-based recommendations, there are no clinical guidelines that inform when and how such spiritual care should be provided. We propose convening a multi-disciplinary workgroup to generate specific and actionable guidelines for incorporating spiritual care in serious illness care. We suggest three workgroup priorities: (1) determining best approaches to identifying patient and family members' spiritual care needs; (2) developing ways to integrate chaplains into routine clinical care; and (3) determining best approaches to communicate availability of spiritual care. Developing these guidelines is an imperative next step to deliver high quality, person and family-centered care.

Differences in honeybee queen pheromones revealed by LC-MS/MS: Reassessing the honest signal hypothesis.

The honest signal hypothesis posits that social insect queens emit pheromonal signals that convey information about fecundity, which workers use to make decisions around investing in direct or indirect fitness. We used liquid chromatography-tandem mass spectrometry to measure honeybee (Apis mellifera) queen retinue pheromone (QRP) in relation to age, laying status, and acceptance using a protocol that enables concurrent metabolomic and lipidomic analyses. Older queens produced higher levels of the QRP components 9-R-hydroxydec-2(E)-enoic acid (9(R)-HDA), linolenic acid (LEA), and 4-hydroxy-3-methoxyphenylethanol (HVA) compared to younger queens, with HVA also correlating with ovary mass. However, ovary mass was not an influential metric for worker decision-making around queen acceptance; therefore, the relationship between HVA and ovary mass is merely an "honest signal" of a non-influential metric. Parallel metabolomic and lipidomic analyses showed that samples cluster according to queen age and mating status, but not ovary mass, revealing many other physiological changes occurring in the queen's early life.

Proof of concept, feasibility, and acceptability of spiritual care assessment and intervention-pediatric with caregivers of children receiving home mechanical ventilation.

Caregivers of children with medical complexity face daily tasks comparable to pediatric critical care nursing with multiple stressors. This may result in emotional and spiritual distress. Caregivers may also rely on their religion and spirituality to cope. Chaplains have the potential to support caregivers in this setting, beginning with spiritual assessment. This study's purpose was to verify the feasibility and acceptability of the Spiritual Care Assessment and Intervention framework adapted for home-based chaplaincy with caregivers of children receiving home mechanical ventilation (SCAI-Peds). A quasi-experimental, proof-of-concept trial with N = 6 caregivers and two board certified chaplains was carried out. SCAI-Peds was acceptable and feasible to caregivers, delivered with high fidelity, and was also acceptable to the chaplains. Home-based intervention delivery may provide more room for reflection and reframing than acute care settings. The results warrant advancing SCAI-Peds beyond the pilot stage.

Invasive procedures and surgery following etranacogene dezaparvovec gene therapy in people with haemophilia B.

BACKGROUND: Little information regarding the management of invasive procedures in people with haemophilia B (HB) after undergoing gene therapy is available. Here, we report the management of invasive procedures in people with severe or moderately severe HB who had previously been treated with etranacogene dezaparvovec in the Phase 2b and Phase 3 HOPE-B clinical trials (NCT03489291, NCT03569891). METHODS: This retrospective analysis included invasive procedures performed within 3 and 2 years following a single infusion of 2x1013 gc/kg of etranacogene dezaparvovec in participants in the Phase 2b and HOPE-B trials, respectively. Data for FIX dosing, duration of postoperative FIX use, FIX activity prior to invasive procedures, and postoperative bleeds were collected and analysed. RESULTS: The analysis included 64 procedures in 29 participants: nine major surgeries, 24 minor surgeries, 11 endoscopies, three endoscopies with biopsy/polypectomy, and 17 dental procedures. Uncontaminated endogenous FIX activity corresponded to mild haemophilia or normal levels prior to 98% of all procedures, with a median endogenous FIX activity of 43.8 IU/dL (range 3.1-113 IU/dL). All major surgeries were managed with exogenous FIX, 67% with ≤4 days of FIX infusion. Most minor surgeries (88%), endoscopies (82%), and dental procedures (94%) were managed with no or a single FIX infusion. Postoperative bleeds occurred after one minor surgery and four dental procedures. There were no symptomatic thrombotic events or FIX inhibitor developments. CONCLUSION: Etranacogene dezaparvovec has the potential to facilitate perioperative management in people with HB by reducing the need for perioperative exogenous FIX and its associated risks.

Prevalence of Long COVID and the Impact on Diabetes Management and Physical Activity Participation in Adults With Type 2 Diabetes: An Australia-wide Cross-sectional Online Survey.

OBJECTIVES: The aim of this research was to understand the prevalence and impact of long COVID on adults with type 2 diabetes (T2D). Specifically, we sought to identify the proportion of adults with T2D who have had COVID-19 and experienced long COVID symptoms. We also explored how these ongoing symptoms impact diabetes management and physical activity participation. METHODS: Our study was carried out using an online survey of adults in Australia with T2D who had confirmed COVID-19 ≥12 weeks before participation. Respondents were asked to report the presence (and severity) of long COVID-19 symptoms, and, for those with long COVID, the impact of their symptoms on diabetes management (blood glucose, body weight) and physical activity participation (activities of daily living, work/study, exercise). RESULTS: Survey responses were provided by 1,046 adults with T2D (median age 61.0 [interquartile range 49.8 to 70.0] years; 56.0% men, 42.1% women, and 1% nonbinary/transgender; median T2D duration 10.0 [5.0 to 18.0] years and median time since COVID-19 infection 33.0 [20.3 to 36.1] weeks). Almost one third (30%) of respondents reported long COVID symptoms (present ≥12 weeks after most recent infection); 40% of respondents with long COVID symptoms reported a worsening of their diabetes management since their COVID-19 infection, with 29% reporting trouble controlling their blood glucose and 43% reporting a higher body weight. Two thirds of respondents with ongoing symptoms reported that these symptoms moderately to severely impacted their ability to perform activities of daily living, work, and/or exercise. The majority of those with long COVID reported reducing the frequency, duration, and/or intensity of exercise since their COVID-19 infection, with 36.1% not yet returning to their preinfection exercise levels; 66% cited ongoing symptoms as the primary reason for these limitations. CONCLUSIONS: Physical activity is a crucial component of diabetes management. However, the high prevalence of long COVID is hindering participation in this population, as well as deleteriously impacting diabetes management. Developing strategies to support adults with T2D and long COVID to recommence safe levels of physical activity is of critical importance.

Utilizing technology for diet and exercise change in complex chronic conditions across diverse environments (U-DECIDE): feasibility randomised controlled trial.

BACKGROUND: Diet and exercise are important components of treatment for complex chronic conditions, however access to allied health support is limited. When available, support is often siloed and fragmented. Digital health incorporating patient choice may help to align health care services with preferences and goals. This study evaluated the implementation of a ubiquitously accessible patient-centred digital health diet and exercise service. METHODS: U-DECIDE was a single-centre, 26-week randomised controlled trial set in kidney and liver disease clinics in a tertiary hospital in Brisbane, Australia. Participants were adults with a complex chronic condition referred for dietetic consultation with at least one feature of the metabolic syndrome. All participants received a dietary consultation, an activity monitor and usual care. Intervention participants were offered one text message per week and access to additional digital health options (increased text message frequency, nutrition app, exercise app, group-based diet and/or exercise video consultations). The primary outcome of feasibility was determined by safety (study-related serious adverse events: SRSAEs), recruitment (≥ 50% eligible patients), retention (≥ 70%), exposure uptake (≥ 75% of intervention group had greater access to health professional contact than comparator) and video consultation adherence (≥ 80% attendance). Secondary outcomes included process evaluation metrics and clinical outcomes. RESULTS: Of 67 participants (intervention n = 33, comparator n = 34), 37 (55%) were men, median (IQR) age was 51 (41-58) years. The most chosen digital health options were the nutrition app (n = 29, 88%) and exercise video consultations (n = 26, 79%). Only one participant chose no additional digital health options. The intervention group had no SRSAEs. The study exceeded targets for recruitment (52%), retention (81%) and exposure uptake (94%). Video consultation adherence was 42%. Engagement across digital health options was inconsistent. CONCLUSIONS: Digital health options incorporating patient choice were feasible and can be offered to people with complex chronic disease as a service model option. TRIAL REGISTRATION: Australia and New Zealand Trials Register: Trial Registration Number: ACTRN12620001282976. Registered 27th November 2020.

Correlative three-dimensional X-ray histology (3D-XRH) as a tool for quantifying mammalian placental structure.

Mammalian placentas exhibit unparalleled structural diversity, despite sharing a common ancestor and principal functions. The bulk of structural studies in placental research has used two-dimensional (2D) histology sectioning, allowing significant advances in our understanding of mammalian placental structure. However, 2D histology sectioning may be limited if it does not provide accurate information of three-dimensional (3D) tissue architecture. Here, we propose correlative 3D X-ray histology (3D-XRH) as a tool with great potential for resolving mammalian placental structures. 3D-XRH involves scanning a formaldehyde-fixed, paraffin embedded (FFPE) tissue block with 3D X-ray microscopy (microCT) prior to histological sectioning to generate a 3D image volume of the embedded tissue piece. The subsequent 2D histology sections can then be correlated back into the microCT image volume to couple histology staining (or immunolabelling) with 3D tissue architecture. 3D-XRH is non-destructive and requires no additional sample preparation than standard FFPE histology sectioning, however the image volume provides 3D morphometric data and can be used to guide microtomy. As such, 3D-XRH introduces additional information to standard histological workflows with minimal effort or disruption. Using primary examples from porcine, bovine, equine, and canine placental samples, we demonstrate the application of 3D-XRH to quantifying placental structure as well as discussing the limitations and future directions of the methodology. The wealth of information derived from 2D histological sectioning in the biomedical, veterinary, and comparative reproductive sciences provides a rich foundation from which 3D-XRH can build on to advance the study of placental structure and function.

Timing determines zooplankton community responses to multiple stressors.

Human activities and climate change cause abiotic factors to fluctuate through time, sometimes passing thresholds for organismal reproduction and survival. Multiple stressors can independently or interactively impact organisms; however, few studies have examined how they interact when they overlap spatially but occur asynchronously. Fluctuations in salinity have been found in freshwater habitats worldwide. Meanwhile, heatwaves have become more frequent and extreme. High salinity pulses and heatwaves are often decoupled in time but can still collectively impact freshwater zooplankton. The time intervals between them, during which population growth and community recovery could happen, can influence combined effects, but no one has examined these effects. We conducted a mesocosm experiment to examine how different recovery times (0-, 3-, 6-week) between salt treatment and heatwave exposure influence their combined effects. We hypothesized that antagonistic effects would appear when having short recovery time, because previous study found that similar species were affected by the two stressors, but effects would become additive with longer recovery time since fully recovered communities would respond to heatwave similar to undisturbed communities. Our findings showed that, when combined, the two-stressor joint impacts changed from antagonistic to additive with increased recovery time between stressors. Surprisingly, full compositional recovery was not achieved despite a recovery period that was long enough for population growth, suggesting legacy effects from earlier treatment. The recovery was mainly driven by small organisms, such as rotifers and small cladocerans. As a result, communities recovering from previous salt exposure responded differently to heatwaves than undisturbed communities, leading to similar zooplankton communities regardless of the recovery time between stressors. Our research bolsters the understanding and management of multiple-stressor issues by revealing that prior exposure to one stressor has long-lasting impacts on community recovery that can lead to unexpected joint effects of multiple stressors.

A Transmission Assay of 'Candidatus Liberibacter asiaticus' Using Citrus Phloem Sap and Topical Feeding to Its Insect Vector, Diaphorina citri.

'Candidatus Liberibacter asiaticus', the putative causal agent of citrus greening disease, is transmitted by the Asian citrus psyllid, Diaphorina citri, in a propagative, circulative, and persistent manner. Unfortunately, 'Ca. L. asiaticus' is not yet available in pure culture to carry out Koch's postulates and to confirm its etiology. When a pure culture is available, an assay to test its infectivity in both the insect vector and the plant host will be crucial. Herein, we described a transmission assay based on the use of phloem sap extracted from infected citrus plants and topical feeding to D. citri nymphs. Phloem sap was collected by centrifugation, diluted with 0.1 M phosphate buffer pH 7.4 containing 20% (wt/vol) sucrose and 0.1% ascorbic acid (wt/vol) as an antioxidant, and delivered to third through fifth instar nymphs by placing droplets on the mouthparts. Nymphs unfolded the stylets and acquired the phloem sap containing the bacterial pathogen. Nymphs were then placed onto Citrus macrophylla seedlings (10 nymphs per seedling) for an inoculation period of 2 weeks. A transmission rate of up to 80% was recorded at 6 months postinoculation. The method could be a powerful tool to test the transmissibility of the bacterial pathogen after various treatments to reduce the viability of the bacteria or to block its transmission. In addition, it might be a potent assay to achieve Koch's postulates if a pure culture of 'Ca. L. asiaticus' becomes available.

Exercise improves surrogate measures of liver histological response in metabolic dysfunction-associated steatotic liver disease.

BACKGROUND AND AIMS: Exercise is recommended for the management of metabolic dysfunction-associated steatotic liver disease (MASLD), yet effects on liver histology remain unknown, especially without significant weight loss. We aimed to examine changes in surrogate measures of liver histological response with exercise training. METHODS: We conducted a post hoc pooled analysis of three randomised controlled trials (duration: 12-20 weeks) comparing aerobic exercise interventions with controls. The primary outcome measure was a ≥30% relative reduction in (MRI-measured) liver fat, as a surrogate measure of liver histological response (the threshold necessary for fibrosis improvement). Secondary outcome measures were changes in other biomarkers of liver fibrosis, anthropometry, body composition and aerobic fitness. RESULTS: Eighty-eight adults (exercise: 54, control: 34; male: 67%) were included with mean (SD) age 51 (11) years and body mass index 33.3 (5.2) kg/m2. Following the intervention, exercise had ~5-fold (OR [95%CI]: 4.86 [1.72, 13.8], p = .002) greater odds of ≥30% relative reduction in MRI-measured liver fat compared with control. This paralleled the improvements in anthropometry (waist and hip circumference reduction), body composition (body fat, visceral and subcutaneous adipose tissue) and aerobic fitness (V̇O2peak, ventilatory threshold and exercise capacity). Importantly, these effects were independent of clinically significant body weight loss (<3% body weight). CONCLUSION: Exercise training led to clinically meaningful improvements in surrogate serum- and imaging-based measures of liver histological change, without clinically meaningful body weight reduction. These data reinforce the weight-neutral benefit of exercise training and suggest that aerobic training may improve liver fibrosis in patients with MASLD.

Skin repair and infection control in diabetic, obese mice using bioactive laser-activated sealants.

Conventional wound approximation devices, including sutures, staples, and glues, are widely used but risk of wound dehiscence, local infection, and scarring can be exacerbated in these approaches, including in diabetic and obese individuals. This study reports the efficacy and quality of tissue repair upon photothermal sealing of full-thickness incisional skin wounds using silk fibroin-based laser-activated sealants (LASEs) containing copper chloride salt (Cu-LASE) or silver nanoprisms (AgNPr-LASE), which absorb and convert near-infrared (NIR) laser energy to heat. LASE application results in rapid and effective skin sealing in healthy, immunodeficient, as well as diabetic and obese mice. Although lower recovery of epidermal structure and function was seen with AgNPr-LASE sealing, likely because of the hyperthermia induced by laser and presence of this material in the wound space, this approach resulted in higher enhancement in recovery of skin biomechanical strength compared to sutures and Cu-LASEs in diabetic, obese mice. Histological and immunohistochemical analyses revealed that AgNPr-LASEs resulted in significantly lower neutrophil migration to the wound compared to Cu-LASEs and sutures, indicating a more muted inflammatory response. Cu-LASEs resulted in local tissue toxicity likely because of effects of copper ions as manifested in the form of a significant epidermal gap and a 'depletion zone', which was a region devoid of viable cells proximal to the wound. Compared to sutures, LASE-mediated sealing, in later stages of healing, resulted in increased angiogenesis and diminished myofibroblast activation, which can be indicative of lower scarring. AgNPr-LASE loaded with vancomycin, an antibiotic drug, significantly lowered methicillin-resistant Staphylococcus aureus (MRSA) load in a pathogen challenge model in diabetic and obese mice and also reduced post-infection inflammation of tissue compared to antibacterial sutures. Taken together, these attributes indicate that AgNPr-LASE demonstrated a more balanced quality of tissue sealing and repair in diabetic and obese mice and can be used for combating local infections, that can result in poor healing in these individuals.

Higher prevalence of sacbrood virus in Apis mellifera (Hymenoptera: Apidae) colonies after pollinating highbush blueberries.

Highbush blueberry pollination depends on managed honey bees (Apis mellifera) L. for adequate fruit sets; however, beekeepers have raised concerns about the poor health of colonies after pollinating this crop. Postulated causes include agrochemical exposure, nutritional deficits, and interactions with parasites and pathogens, particularly Melisococcus plutonius [(ex. White) Bailey and Collins, Lactobacillales: Enterococcaceae], the causal agent of European foulbrood disease, but other pathogens could be involved. To broadly investigate common honey bee pathogens in relation to blueberry pollination, we sampled adult honey bees from colonies at time points corresponding to before (t1), during (t2), at the end (t3), and after (t4) highbush blueberry pollination in British Columbia, Canada, across 2 years (2020 and 2021). Nine viruses, as well as M. plutonius, Vairimorpha ceranae, and V. apis [Tokarev et al., Microsporidia: Nosematidae; formerly Nosema ceranae (Fries et al.) and N. apis (Zander)], were detected by PCR and compared among colonies located near and far from blueberry fields. We found a significant interactive effect of time and blueberry proximity on the multivariate pathogen community, mainly due to differences at t4 (corresponding to ~6 wk after the beginning of the pollination period). Post hoc comparisons of pathogens in near and far groups at t4 showed that detections of sacbrood virus (SBV), which was significantly higher in the near group, not M. plutonius, was the primary driver. Further research is needed to determine if the association of SBV with highbush blueberry pollination is contributing to the health decline that beekeepers observe after pollinating this crop.

Patients' acceptability of self-selected digital health services to support diet and exercise among people with complex chronic conditions: Mixed methods study.

Objective: The acceptability of being offered a choice from a suite of digital health service options to support optimal diet and exercise behaviors in adults with complex chronic conditions was evaluated. This study sought to understand many areas of acceptability including satisfaction, ease of use, usefulness and user appropriateness and perceived effectiveness. Methods: This mixed-methods study was embedded within a randomized-controlled feasibility trial providing digital health services managing diet and exercise for adults from specialist kidney and liver disease clinics. Post study surveys and semistructured interviews were used to determine patients' acceptability of the trial interventions. Quantitative (surveys) and qualitative (surveys and interviews) results were merged using integrative analysis and mapped to each construct of the modified version of the Theoretical Framework of Acceptability. Results: Seventeen interviews (intervention group) and 50 surveys (n = 24 intervention, n = 26 comparator) completed from a possible 67 participants were analyzed. In the intervention group, the survey results revealed high areas of acceptability for the digital health services including overall support received, ease of use, timely advice and feeling safe. The interviews also revealed high areas of acceptability including convenience, ability to adopt healthier behaviors and having regular interactions with health professionals. However, the interviews also revealed lower areas of acceptability as a result of absence of individualization, low digital literacy, and limitations from life circumstances. Conclusions: Recipients of digital health services that supported diet and exercise interventions found these useful, effective, and safe. Individualized care, technical support and patient confidence remain important to improve the acceptability of digital health service interventions.

M. tuberculosis PrrA binds the dosR promoter and regulates mycobacterial adaptation to hypoxia.

The PrrAB two-component system (TCS) is essential for Mycobacterium tuberculosis viability. Previously, it was demonstrated that PrrA binds DNA in the absence of PrrB-mediated transphosphorylation and that non-cognate serine/threonine-kinases phosphorylate PrrA threonine-6 (T6). Therefore, we investigated the differential binding affinity and regulatory properties of the M. tuberculosis-derived wild-type PrrA, PrrA phosphomimetic (D58E, T6E), and PrrA phosphoablative (D58A, T6A) proteins with the prrAMtb, dosRMtb, and cydAMtb genes. While we hypothesized greater DNA binding affinity and more pronounced regulation by PrrA phosphomimetic variants, recombinant, wild-type PrrAMtb bound DNA with greatest affinity. Collectively, wild-type PrrAMtb recombinant protein displayed the highest binding affinity to the dosRMtb promoter (KD 3.46 ± 2.09 nM), followed by the prrAMtb promoter (KD 9.00 ± 2.66 nM). To establish PrrAMtb regulatory activity, we constructed M. smegmatis ΔprrABMsmeg::prrAMtb strains with each of the PrrAMtb variants and extrachromosomal prrAMtb, dosRMtb, and cydAMtb promoter-mCherry reporter fusions. Our findings showed that PrrAMtb is autoregulatory and induces dosRMtb expression only during in vitro, hypoxic growth. Combined expression of prrABMtb in M. smegmatis ΔprrAB significantly induced cydAMtb promoter-mCherry expression. Our studies advanced the understanding of PrrA function and PrrAB phosphorylation-mediated regulatory mechanisms and control of mycobacterial dosR and cydA hypoxic and low-oxygen responsive genes.

Shenling Baizhu San ameliorates non-alcoholic fatty liver disease in mice by modulating gut microbiota and metabolites.

Purpose: The prevalence of non-alcoholic fatty liver disease (NAFLD) and its related mortality is increasing at an unprecedented rate. Traditional Chinese medicine (TCM) has been shown to offer potential for early prevention and treatment of NAFLD. The new mechanism of "Shenling Baizhu San" (SLBZS) is examined in this study for the prevention and treatment of NAFLD at the preclinical level. Methods: Male C57BL/6J mice were randomly divided into three groups: normal diet (ND), western diet + CCl4 injection (WDC), and SLBZS intervention (WDC + SLBZS). Body weights, energy intake, liver enzymes, pro-inflammatory factors, and steatosis were recorded in detail. Meanwhile, TPH1, 5-HT, HTR2A, and HTR2B were tested using qRT-PCR or ELISA. Dynamic changes in the gut microbiota and metabolites were further detected through the 16S rRNA gene and untargeted metabolomics. Results: SLBZS intervention for 6 weeks could reduce the serum and liver lipid profiles, glucose, and pro-inflammatory factors while improving insulin resistance and liver function indexes in the mice, thus alleviating NAFLD in mice. More importantly, significant changes were found in the intestinal TPH-1, 5-HT, liver 5-HT, and related receptors HTR2A and HTR2B. The 16S rRNA gene analysis suggested that SLBZS was able to modulate the disturbance of gut microbiota, remarkably increasing the relative abundance of probiotics (Bifidobacterium and Parvibacter) and inhibiting the growth of pro-inflammatory bacteria (Erysipelatoclostridium and Lachnoclostridium) in mice with NAFLD. Combined with metabolomics in positive- and negative-ion-mode analyses, approximately 50 common differential metabolites were selected via non-targeted metabolomics detection, which indicated that the targeting effect of SLBZS included lipid metabolites, bile acids (BAs), amino acids (AAs), and tryptophan metabolites. In particular, the lipid metabolites 15-OxEDE, vitamin D3, desoxycortone, and oleoyl ethanol amide were restored by SLBZS. Conclusion: Integrating the above results of multiple omics suggests that SLBZS ameliorates NAFLD via specific gut microbiota, gut-derived 5-HT, and related metabolites to decrease fat accumulation in the liver and inflammatory responses.

Physical activity volume, frequency, and intensity: Associations with hypertension and obesity over 21 years in Australian women.

BACKGROUND: Optimal patterns of accrual of recommended levels of physical activity (PA) for prevention of hypertension and obesity are not known. The overall aim of this study was to investigate whether different patterns of accumulation of PA are differentially associated with hypertension and obesity in Australian women over 21 years. Specifically, we investigated whether, for the same weekly volume of PA, the number of sessions (frequency) and vigorousness of PA (intensity) were associated with a reduction in the occurrence of hypertension and obesity in women. METHODS: Data from the 1973-1978 and 1946-1951 cohorts of the Australian Longitudinal Study on Women's Health were analyzed (n = 20,588; 12%-16% with a Bachelor's or higher degree). Self-reported PA, hypertension, height, and weight were collected using mail surveys every 3 years from 1998/2000 to 2019/2021. Generalized Estimating Equation models with a 3-year lag model were used to investigate the association of PA volume (metabolic equivalent min/week) (none; 33-499; 500-999; ≥1000, weekly frequency (none; 1-2 times; 3-4 times; 5-7 times; ≥8 times), and the proportion of vigorous PA to total volume of PA (none; 0%; 1%-33%; 34%-66%; 67%-100%) with odds of hypertension and obesity from 2000 to 2021. RESULTS: The cumulative incidence of hypertension was 6% in the 1973-1978 and 23% in the 1946-1951 cohort; 27% of women in the 1973-1978; and 15% in the 1946-1951 cohort developed obesity over the period. Overall, a higher volume of PA was associated with reduced odds of hypertension and obesity. When the volume of PA was considered, the odds of hypertension did not vary according to the frequency or intensity of PA. However, increased proportion of vigorous PA to the total volume of PA was associated with a small additional reduction in the risk of obesity. CONCLUSION: PA volume appears to be more important than the pattern of accumulation for the prevention of hypertension and obesity. Incorporating more sessions, particularly of vigorous-intensity PA, may provide extra benefits for the prevention of obesity.

Anticoagulation and vascular anomalies.

A State of the Art lecture titled "Anticoagulation and Vascular Anomalies" was presented at the International Society on Thrombosis and Haemostasis (ISTH) Congress in 2023. Vascular anomalies have been classified by the International Society for the Study of Vascular Anomalies into vascular tumors and vascular malformations. Although some vascular tumors, such as tufted angioma and kaposiform hemangioendothelioma, and other vascular malformations can present with coagulation aberrancies, these are not generally managed with anticoagulation. A subclassification of vascular malformations includes slow-flow vascular malformations. It is this subgroup specifically that has a high risk of venous thromboembolism (VTE) and morbidity associated with coagulopathy that may be present. In these select cases, anticoagulation may be indicated to reduce the risk of VTE, treat VTE, or manage localized thrombosis in the malformation that causes significant pain and reduced quality of life. There are established risk factors for VTE in these patients that will be reviewed. Finally, we summarize relevant new data on this topic presented during the 2023 ISTH Congress.

Evaluating the Potential of a Novel Metabolic Syndrome Severity Score to Inform Exercise Interventions for People with Complex Chronic Conditions.

Aims: Exercise interventions positively affect numerous cardiometabolic risk factors. To better evaluate the health effects of exercise training, it may be more appropriate to evaluate risk factors together. The Metabolic Syndrome Severity Score (MetSSS) is a composite score representing cardiometabolic risk. Purpose: To evaluate the relationships between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS in a heterogenous sample of people with complex chronic disease. Material and Methods: Fifty-three people with kidney or liver disease and at least one feature of the metabolic syndrome (MetS) were included. Pearson correlations were conducted between physical activity, neuromuscular fitness, exercise capacity, and the MetSSS. Linear regressions were performed for multi-level categorical variables. Independent variables with an association with MetSSS (P ≤ 0.2) were included in a multiple regression analysis. Results: The 6-minute walk test (6MWT) distance was inversely and independently associated with MetSSS [standardized beta coefficient (ß) = -0.31, P = 0.04]. No relationship was found between MetSSS and physical activity or neuromuscular fitness. Mean 6MWT in the highest tertile was 550 m (range: 505-620 m) and 346 m (range: 233-408 m) in the lowest. The analysis showed a medium-large between-group effect for the difference in MetSSS for the lowest and highest tertile of 6MWT [Eta squared (η2) = 0.16, P = 0.01]. Conclusions: Exercise capacity was inversely and independently associated with MetSSS in people with complex chronic disease. Clinical trials with exercise interventions are needed to further investigate if improvements in exercise capacity result in clinically significant changes in the MetSSS.