Ring-opening metathesis polymerization of N-methylpyridinium-fused norbornenes to access antibacterial main-chain cationic polymers.

Cationic polymers have been identified as a promising type of antibacterial molecules, whose bioactivity can be tuned through structural modulation. Recent studies suggest that the placement of the cationic groups close to the core of the polymeric architecture rather than on appended side chains might improve both their bioactivity and selectivity for bacterial cells over mammalian cells. However, antibacterial main-chain cationic polymers are typically synthesized via polycondensations, which do not afford precise and uniform molecular design. Therefore, accessing main-chain cationic polymers with high degrees of molecular tunability hinges upon the development of controlled polymerizations tolerating cationic motifs (or cation progenitors) near the propagating species. Herein, we report the synthesis and ring-opening metathesis polymerization (ROMP) of N-methylpyridinium-fused norbornene monomers. The identification of reaction conditions leading to a well-controlled ROMP enabled structural diversification of the main-chain cationic polymers and a study of their bioactivity. This family of polyelectrolytes was found to be active against both Gram-negative (Escherichia coli) and Gram-positive (Methicillin-resistant Staphylococcus aureus) bacteria with minimal inhibitory concentrations as low as 25 µg/mL. Additionally, the molar mass of the polymers was found to impact their hemolytic activity with cationic polymers of smaller degrees of polymerization showing increased selectivity for bacteria over human red blood cells.

Proportion and number of cancer cases and deaths attributable to behavioral risk factors in Vietnam.

Identifying modifiable risk factors that contribute to cancer is essential in setting up preventive strategies. Therefore, this study aimed to estimate the number and proportion of cancer cases and deaths attributable to five behavior-related risk factors-tobacco smoking, second-hand smoking, alcohol consumption, high body mass index and insufficient physical activity in Vietnam in 2020. Population attributable fractions were calculated for relationships of risk factors and cancer types based on sufficient evidence according to IARC or strong evidence according to WCRF/AICR. Relative risks were retrieved from meta-analyses where possible. Prevalence of risk factors was obtained from the most current available nationally representative population surveys in Vietnam. Cancer cases and deaths were obtained from GLOBOCAN 2020. An estimated 40.5% of all cancer cases in men (39 924 cases) and 7.8% in women (6542 cases) were attributable to these risk factors. The proportions of cancer deaths attributable to these risk factors were 44.0% in men (32 807 cases) and 8.9% in women (4235 cases). Tobacco smoking was the leading cause of cancer cases and deaths in men, followed by alcohol consumption and high BMI. In women, high BMI accounted for the highest proportion of cancer cases and second-hand smoking accounted for the highest proportion of cancer deaths. Lung and upper aerodigestive tract cancer cases and deaths could have been reduced at least by half if these risk factors had been eliminated. To reduce cancer incidence and mortality, preventive actions focusing on tobacco control are likely to have the most significant impact, especially in men.

Biallelic variants in RNU12 cause CDAGS syndrome.

CDAGS Syndrome is a rare congenital disorder characterized by Craniosynostosis, Delayed closure of the fontanelles, cranial defects, clavicular hypoplasia, Anal and Genitourinary malformations, and Skin manifestations. We performed whole exome and Sanger sequencing to identify the underlying molecular cause in five patients with CDAGS syndrome from four distinct families. Whole exome sequencing revealed biallelic rare variants that disrupt highly conserved nucleotides within the RNU12 gene. RNU12 encodes a small nuclear RNA that is a component of the minor spliceosome and is essential for minor intron splicing. Targeted sequencing confirmed allele segregation within the four families. All five patients shared the same rare mutation NC_000022.10:g.43011402C>T, which alters a highly conserved nucleotide within the precursor U12 snRNA 3' extension. Each of them also carried a rare variant on the other allele that either disrupts the secondary structure or the Sm binding site of the RNU12 snRNA. Whole transcriptome sequencing analysis of lymphoblastoid cells identified 120 differentially expressed genes, and differential alternative splicing analysis indicated there was an enrichment of alternative splicing events in the patient. These findings provide evidence of the involvement of RNU12 in craniosynostosis, anal and genitourinary patterning, and cutaneous disease.

Age-associated insolubility of parkin in human midbrain is linked to redox balance and sequestration of reactive dopamine metabolites.

The mechanisms by which parkin protects the adult human brain from Parkinson disease remain incompletely understood. We hypothesized that parkin cysteines participate in redox reactions and that these are reflected in its posttranslational modifications. We found that in post mortem human brain, including in the Substantia nigra, parkin is largely insoluble after age 40 years; this transition is linked to its oxidation, such as at residues Cys95 and Cys253. In mice, oxidative stress induces posttranslational modifications of parkin cysteines that lower its solubility in vivo. Similarly, oxidation of recombinant parkin by hydrogen peroxide (H2O2) promotes its insolubility and aggregate formation, and in exchange leads to the reduction of H2O2. This thiol-based redox activity is diminished by parkin point mutants, e.g., p.C431F and p.G328E. In prkn-null mice, H2O2 levels are increased under oxidative stress conditions, such as acutely by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine toxin exposure or chronically due to a second, genetic hit; H2O2 levels are also significantly increased in parkin-deficient human brain. In dopamine toxicity studies, wild-type parkin, but not disease-linked mutants, protects human dopaminergic cells, in part through lowering H2O2. Parkin also neutralizes reactive, electrophilic dopamine metabolites via adduct formation, which occurs foremost at the primate-specific residue Cys95. Further, wild-type but not p.C95A-mutant parkin augments melanin formation in vitro. By probing sections of adult, human midbrain from control individuals with epitope-mapped, monoclonal antibodies, we found specific and robust parkin reactivity that co-localizes with neuromelanin pigment, frequently within LAMP-3/CD63+ lysosomes. We conclude that oxidative modifications of parkin cysteines are associated with protective outcomes, which include the reduction of H2O2, conjugation of reactive dopamine metabolites, sequestration of radicals within insoluble aggregates, and increased melanin formation. The loss of these complementary redox effects may augment oxidative stress during ageing in dopamine-producing cells of mutant PRKN allele carriers, thereby enhancing the risk of Parkinson's-linked neurodegeneration.

Maternal choline supplementation ameliorates Alzheimer's disease pathology by reducing brain homocysteine levels across multiple generations.

The lack of effective treatments for Alzheimer's disease (AD) is alarming, considering the number of people currently affected by this disorder and the projected increase over the next few decades. Elevated homocysteine (Hcy) levels double the risk of developing AD. Choline, a primary dietary source of methyl groups, converts Hcy to methionine and reduces age-dependent cognitive decline. Here, we tested the transgenerational benefits of maternal choline supplementation (ChS; 5.0 g/kg choline chloride) in two generations (Gen) of APP/PS1 mice. We first exposed 2.5-month-old mice to the ChS diet and allowed them to breed with each other to generate Gen-1 mice. Gen-1 mice were exposed to the ChS diet only during gestation and lactation; once weaned at postnatal day 21, Gen-1 mice were then kept on the control diet for the remainder of their life. We also bred a subset of Gen-1 mice to each other and obtained Gen-2 mice; these mice were never exposed to ChS. We found that ChS reduced Aß load and microglia activation, and improved cognitive deficits in old Gen-1 and Gen-2 APP/PS1 mice. Mechanistically, these changes were linked to a reduction in brain Hcy levels in both generations. Further, RNA-Seq data from APP/PS1 hippocampal tissue revealed that ChS significantly changed the expression of 27 genes. These genes were enriched for inflammation, histone modifications, and neuronal death functional classes. Our results are the first to demonstrate a transgenerational benefit of ChS and suggest that modifying the maternal diet with additional choline reduces AD pathology across multiple generations.

Noninvasive imaging of renal urea handling by CEST-MRI.

PURPOSE: Renal function is characterized by concentration of urea for removal in urine. We tested urea as a CEST-MRI contrast agent for measurement of the concentrating capacity of distinct renal anatomical regions. METHODS: The CEST contrast of urea was examined using phantoms with different concentrations and pH levels. Ten C57BL/6J mice were scanned twice at 7 T, once following intraperitoneal injection of 2M 150 µL urea and separately following an identical volume of saline. Kidneys were segmented into regions encompassing the cortex, outer medulla, and inner medulla and papilla to monitor spatially varying urea concentration. Z-spectra were acquired before and 20 minutes after injection, with dynamic scanning of urea handling performed in between via serial acquisition of CEST images acquired following saturation at +1 ppm. RESULTS: Phantom experiments revealed concentration and pH-dependent CEST contrast of urea that was both acid- and base-catalyzed. Z-spectra acquired before injection showed significantly higher CEST contrast in the inner medulla and papilla (2.3% ± 1.9%) compared with the cortex (0.15% ± 0.75%, P = .011) and outer medulla (0.12% ± 0.58%, P = .008). Urea infusion increased CEST contrast in the inner medulla and papilla by 2.1% ± 1.9% (absolute), whereas saline infusion decreased CEST contrast by -0.5% ± 2.0% (absolute, P = .028 versus urea). Dynamic scanning revealed that thermal drift and diuretic status are confounding factors. CONCLUSION: Urea CEST has a potential of monitoring renal function by capturing the spatially varying urea concentrating ability of the kidneys.

Bilateral Limb-Shaking Transient Ischemic Attacks.

Limb shaking is a rare manifestation of transient ischemic attacks (TIA) associated with carotid occlusion, mostly unilateral events. We describe the case of a 69 year-old man who presented with repeated episodes of irregular jerking movements in the bilateral upper and lower extremities, precipitated by standing up. Cerebral angiograms revealed occlusion of both internal carotid arteries, and the patient's symptoms responded to targeted blood pressure management. Physicians should be mindful of bilateral limb-shaking TIA when presented with bilateral paroxysmal events that can mimic seizures or orthostatic hyperkinesia.

The Factor Structure of Vocabulary: An Investigation of Breadth and Depth of Adults with Low Literacy Skills.

The purpose of this study was to examine the factor structure of vocabulary. We believe that not only is vocabulary multidimensional, but depth of vocabulary knowledge should also be assessed with multiple measures since it too, is composed of multiple aspects. Furthermore, to explore the predictive validity of the different aspects of vocabulary knowledge, we assessed the relationship between vocabulary breadth, vocabulary depth, and reading comprehension in adults with low literacy skills. The participants were 103 adults. They completed 12 tasks that have been used in past studies to measure vocabulary breadth, depth, and reading comprehension. We had several important findings. First, we confirmed that all of the assessments were highly reliable for adults with low literacy skills. Second, the results of the factor analysis indicated two distinct vocabulary factors. Finally, both breadth and depth contribute independently to explaining variance in reading comprehension. Implications for vocabulary measurement are suggested.

Catheter ablation of ventricular tachycardia in nonischemic cardiomyopathy: A propensity score-matched analysis of in-hospital outcomes in the United States.

INTRODUCTION: Monomorphic ventricular tachycardia (VT) is an important cause of morbidity and mortality. Use and outcome data of catheter ablation for VT in nonischemic cardiomyopathy (NICM) are limited. METHODS AND RESULTS: We obtained data from the 2003-2014 National Inpatient Sample databases. We used propensity score matching to compare patients undergoing catheter ablation versus medical therapy of VT related to NICM, and described the temporal trends in utilization and in-hospital outcomes of catheter ablation of VT in patients with NICM in the United States. From 2003 to 2014, of 133,529 patients hospitalized with the principal diagnosis of VT in NICM, 14,651 (11.0%) underwent catheter ablation. In this period, there was an increasing trend in utilization of catheter ablation (9.3% in 2003-2004 to 12.1% in 2003-2014, adjusted OR [per year], 1.12; 95% CI, 1.08-1.16; Ptrend  < 0.001). After propensity score matching, in-hospital mortality occurred in 172 of 14,318 (1.2%) patients in the catheter ablation group, compared with 297 of 14,156 (2.1%) of patients undergoing medical therapy (47% lower; 43% relative difference [adjusted OR, 0.53; 95% CI, 0.43-0.66]). CONCLUSIONS: In patients with NICM, catheter ablation of VT is associated with lower in-hospital mortality compared with those managed medically. The utilization rates of CA for VT related to NICM have increased in the past decade. Adequately powered randomized trials will be necessary to confirm these findings.

Contribution of the two genes encoding histone variant h3.3 to viability and fertility in mice.

Histones package DNA and regulate epigenetic states. For the latter, probably the most important histone is H3. Mammals have three near-identical H3 isoforms: canonical H3.1 and H3.2, and the replication-independent variant H3.3. This variant can accumulate in slowly dividing somatic cells, replacing canonical H3. Some replication-independent histones, through their ability to incorporate outside S-phase, are functionally important in the very slowly dividing mammalian germ line. Much remains to be learned of H3.3 functions in germ cell development. Histone H3.3 presents a unique genetic paradigm in that two conventional intron-containing genes encode the identical protein. Here, we present a comprehensive analysis of the developmental effects of null mutations in each of these genes. H3f3a mutants were viable to adulthood. Females were fertile, while males were subfertile with dysmorphic spermatozoa. H3f3b mutants were growth-deficient, dying at birth. H3f3b heterozygotes were also growth-deficient, with males being sterile because of arrest of round spermatids. This sterility was not accompanied by abnormalities in sex chromosome inactivation in meiosis I. Conditional ablation of H3f3b at the beginning of folliculogenesis resulted in zygote cleavage failure, establishing H3f3b as a maternal-effect gene, and revealing a requirement for H3.3 in the first mitosis. Simultaneous ablation of H3f3a and H3f3b in folliculogenesis resulted in early primary oocyte death, demonstrating a crucial role for H3.3 in oogenesis. These findings reveal a heavy reliance on H3.3 for growth, gametogenesis, and fertilization, identifying developmental processes that are particularly susceptible to H3.3 deficiency. They also reveal partial redundancy in function of H3f3a and H3f3b, with the latter gene being generally the most important.

Sexual Dimorphic Pattern of Renal Transporters and Electrolyte Homeostasis.

Compared with males, females have lower BP before age 60, blunted hypertensive response to angiotensin II, and a leftward shift in pressure natriuresis. This study tested the concept that this female advantage associates with a distinct sexual dimorphic pattern of transporters along the nephron. We applied quantitative immunoblotting to generate profiles of transporters, channels, claudins, and selected regulators in both sexes and assessed the physiologic consequences of the differences. In rats, females excreted a saline load more rapidly than males did. Compared with the proximal tubule of males, the proximal tubule of females had greater phosphorylation of Na+/H+ exchanger isoform 3 (NHE3), distribution of NHE3 at the base of the microvilli, and less abundant expression of Na+/Pi cotransporter 2, claudin-2, and aquaporin 1. These changes associated with less bicarbonate reabsorption and higher lithium clearance in females. The distal nephrons of females had a higher abundance of total and phosphorylated Na+/Cl- cotransporter (NCC), claudin-7, and cleaved forms of epithelial Na+ channel (ENaC) α and γ subunits, which associated with a lower baseline plasma K+ concentration. A K+-rich meal increased the urinary K+ concentration and decreased the level of renal phosphorylated NCC in females. Notably, we observed similar abundance profiles in female versus male C57BL/6 mice. These results define sexual dimorphic phenotypes along the nephron and suggest that lower proximal reabsorption in female rats expedites excretion of a saline load and enhances NCC and ENaC abundance and activation, which may facilitate K+ secretion and set plasma K+ at a lower level.

MutY DNA Glycosylase Protects Cells From Tumor Necrosis Factor Alpha-Induced Necroptosis.

Numerous studies have implied that mutY DNA glycosylase (MYH) is involved in the repair of post-replicative mispairs and plays a critical role in the base excision repair pathway. Recent in vitro studies have shown that MYH interacts with tumor necrosis factor receptor type 1-associated death domain (TRADD), a key effector protein of tumor necrosis factor receptor-1 (TNFR1) signaling. The association between MYH and TRADD is reversed during tumor necrosis factor alpha (TNF-α)- and camptothecin (CPT)-induced apoptosis, and enhanced during TNF-α-induced survival. After investigating the role of MYH interacts with various proteins following TNF-α stimulation, here, we focus on MYH and TRADD interaction functions in necroptosis and its effects to related proteins. We report that the level of the MYH and TRADD complex was also reduced during necroptosis induced by TNF-α and zVAD-fmk. In particular, we also found that MYH is a biologically important necrosis suppressor. Under combined TNF-α and zVAD-fmk treatment, MYH-deficient cells were induced to enter the necroptosis pathway but primary mouse embryonic fibroblasts (MEFs) were not. Necroptosis in the absence of MYH proceeds via the inactivation of caspase-8, followed by an increase in the formation of the kinase receptor- interacting protein 1 (RIP1)-RIP3 complex. Our results suggested that MYH, which interacts with TRADD, inhibits TNF-α necroptotic signaling. Therefore, MYH inactivation is essential for necroptosis via the downregulation of caspase-8. J. Cell. Biochem. 118: 1827-1838, 2017. © 2017 Wiley Periodicals, Inc.

Visualization of the physical and functional interaction between hMYH and hRad9 by Dronpa bimolecular fluorescence complementation.

BACKGROUND: Human MutY glycosylase homolog (hMYH), a component of the base excision repair pathway, is responsible for the generation of apurinic/apyrimidinic sites. Rad9-Rad1-Hus1 (9-1-1) is a heterotrimeric protein complex that plays a role in cell cycle checkpoint control and DNA repair. In humans, hMYH and 9-1-1 interact through Hus1 and to a lesser degree with Rad1 in the presence of DNA damage. In Saccharomyces pombe, each component of the 9-1-1 complex interacts directly with SpMYH. The glycosylase activity of hMYH is stimulated by Hus1 and the 9-1-1 complex and enhanced by DNA damage treatment. Cells respond to different stress conditions in different manners. Therefore, we investigated whether Rad9 interacted with hMYH under different stresses. Here, we identified and visualized the interaction between hRad9 and hMYH and investigated the functional consequences of this interaction. RESULTS: Co-IP and BiFC indicates that hMYH interacts with hRad9. As shown by GST-pull down assay, this interaction is direct. Furthermore, BiFC with deletion mutants of hMYH showed that hRad9 interacts with N-terminal region of hMYH. The interaction was enhanced by hydroxyurea (HU) treatment. mRNA and protein levels of hMYH and hRad9 were increased following HU treatment. A marked increase in p-Chk1 (S345) and p-Cdk2 (T14, Y15) was observed. But this phosphorylation decreased in siMYH- or siRad9-transfected cells, and more pronounced decrease observed in co-transfected cells. CONCLUSIONS: Our data reveal that hRad9 interacts directly with N-terminal region of hMYH. This interaction is enhanced by HU treatment. Knockdown of one or both protein result in decreasing Chk1 and Cdk2 phosphorylation. Since both protein functions in the early detection of DNA damage, we suggest that this interaction occurs early in DNA damage pathway.

Pregnancy in Infertile Patient after Intrauterine Adhesiolysis by Multitherapeutic Strategy: A Case Report and Mini-review.

Asherman's syndrome, characterized by intrauterine adhesions (IUAs), represents a significant challenge in the field of female infertility. Hysteroscopic adhesiolysis has emerged as the gold standard for both the diagnosis and treatment of Asherman's syndrome. Understanding the intricate relationship between Asherman's syndrome, uterine adhesiolysis, and infertility is crucial for guiding comprehensive and effective management strategies. The success of the treatment is contingent upon preventing adhesion recurrence, particularly in cases of severe IUAs. This is the first case, in which we employed a multifaceted preventive approach, utilizing hyaluronic gel, Foley balloon, hormonal therapy, and platelet-rich plasma, achieving successful pregnancy following embryo transfer despite the presence of severe IUAs. The patient, a 35-year-old female, underwent one cesarean section following in vitro fertilization and required dilation and curettage due to retained products of conception. The patient presented with oligohemorrhage, and the uterine lining was thin while using hormones for endometrial preparation. The diagnosis of severe IUAs was confirmed through ultrasound and hysteroscopic examination of the uterine cavity. The patient underwent hysteroscopic adhesiolysis with a preventive approach using a combination of methods. Subsequently, the patient underwent a second-look hysteroscopy to assess the uterine cavity and achieved successful embryo transfer. The patient carried the pregnancy to 38 weeks and underwent repeated cesarean section due to the vertex-vertex presentation of the twins.

Bridging biosafety and biosecurity gaps: DURC and ePPP policy insights from U.S. institutions.

Overview: This study provides empirical data on the knowledge and practices of biosafety and biosecurity professionals and researchers involved in research on enhanced Potential Pandemic Pathogens (ePPPs) and Dual Use Research of Concern (DURC) within various U.S. sectors. The goal is to improve public health interventions and oversight for DURC and ePPP, contributing valuable insights for policy development. A notable finding was the association between larger biosafety/biosecurity teams and a higher likelihood of conducting high-risk biological research. Methods: A survey of 541 biosafety and biosecurity professionals was conducted between March 8 and 10 April 2024, with results analyzed using SAS at a significance level of 0.05. The study received approval from the Institutional Review Boards (IRBs) at Arizona State University and the University of Nevada, Reno. Results: Government organizations were more likely to conduct DURC compared to other sectors (e.g., Academic, Commercial, Consulting). Public institutions reviewed more experiments outside the scope of the U.S. DURC Policy than private for-profit institutions. Institutions with larger biosafety/biosecurity teams reported greater research activity and more effective non-compliance reporting mechanisms (e.g., anonymous hotlines, reporting forms). Additionally, financial support and the challenges of policy implementation varied significantly across sectors. Discussion: The findings emphasize the need for appropriate staffing and resource allocation for high-risk biosafety and biosecurity research. A differentiated regulatory approach and equitable distribution of resources are essential for effective oversight. Moreover, robust non-compliance reporting systems are critical to mitigating the risks associated with DURC and ePPP research.

Enhancing Vagal Tone, Modulating Heart Rate Variability with Auricular Acupressure at Point Zero: A Randomized Controlled Trial.

Introduction: Point Zero located within the vagus nerve's auricular branch shows promise in addressing imbalances. This study aims to explore its effects on vagal activity using auricular acupressure (AA), measured through heart rate variability (HRV). Methods: This single-blinded randomized controlled trial involved 114 healthy volunteers randomly assigned to receive AA (AA group, n = 57) or sham-AA (SA group, n = 57) at Point Zero. The 30-minute procedure comprised six stages: T1 and T2 (pre-intervention), T3 to T5 (intervention), and T6 (post-intervention). Interventions involving 30-s acupoint pressure stimulations at T3 and T5. The HRV-measured outcomes included heart rate (HR), standard deviation of R-R intervals (SDNN), root mean square of successive RR interval differences (RMSSD), natural logarithm of low-frequency power (LnLF), and natural logarithm of high-frequency power (LnHF). In addition, respiratory rate (RR) was monitored for its stability. Results: The AA group demonstrated a significant decrease in HR and increases in SDNN, RMSSD, and LnHF from stages T3 to T6 compared with T1 (baseline), notably prominent at T3 (median changes [25th; 75th percentiles]: -2 [-5; -1], 17.85 [9.65; 31.72], 4.9 [1.08; 10.65], 0.26 [0.00; 0.62], respectively) and T5 (-3 [-6; -1], 19.45 [10.6; 32.89], 6.17 [-0.17; 16.34], 0.40 [-0.14; 0.83], respectively), while the SA group did not. LnLF showed nonsignificant alterations, and RR remained stable in both groups. Despite minor HRV fluctuations, the AA group consistently displayed significantly higher changes in SDNN and RMSSD compared with the SA group from T3 onwards. HR remained unchanged at T6, and LnHF significantly differed only at T5. Conclusion: AA at Point Zero may promptly enhance vagal activity, evident in the modulation of HRV, notably pronounced with pressure stimulation, and can be sustained for at least 5 min. Further studies are needed to assess its long-term effectiveness and efficacy in preventing or treating patients.(Clinical Trial Registration: NCT05586698).

Impact of multimorbidity and complex multimorbidity on healthcare utilisation in older Australian adults aged 45 years or more: a large population-based cross-sectional data linkage study.

OBJECTIVES: As life expectancy increases, older people are living longer with multimorbidity (MM, co-occurrence of ≥2 chronic health conditions) and complex multimorbidity (CMM, ≥3 chronic conditions affecting ≥3 different body systems). We assessed the impacts of MM and CMM on healthcare service use in Australia, as little was known about this. DESIGN: Population-based cross-sectional data linkage study. SETTING: New South Wales, Australia. PARTICIPANTS: 248 496 people aged ≥45 years who completed the Sax Institute's 45 and Up Study baseline questionnaire. PRIMARY OUTCOME: High average annual healthcare service use (≥2 hospital admissions, ≥11 general practice visits and ≥2 emergency department (ED) visits) during the 3-year baseline period (year before, year of and year after recruitment). METHODS: Baseline questionnaire data were linked with hospital, Medicare claims and ED datasets. Poisson regression models were used to estimate adjusted and unadjusted prevalence ratios for high service use with 95% CIs. Using a count of chronic conditions (disease count) as an alternative morbidity metric was requested during peer review. RESULTS: Prevalence of MM and CMM was 43.8% and 15.5%, respectively, and prevalence increased with age. Across three healthcare settings, MM was associated with a 2.02-fold to 2.26-fold, and CMM was associated with a 1.83-fold to 2.08-fold, increased risk of high service use. The association was higher in the youngest group (45-59 years) versus the oldest group (≥75 years), which was confirmed when disease count was used as the morbidity metric in sensitivity analysis.When comparing impact using three categories with no overlap (no MM/CMM, MM with no CMM, and CMM), CMM had greater impact than MM across all settings. CONCLUSION: Increased healthcare service use among older adults with MM and CMM impacts on the demand for primary care and hospital services. Which of MM or CMM has greater impact on risk of high healthcare service use depends on the analytic method used. Ageing populations living longer with increasing burdens of MM and CMM will require increased Medicare funding and provision of integrated care across the healthcare system to meet their complex needs.

Adding thread-embedding acupuncture to auricular acupuncture enhances short-term weight reduction in overweight and obesity: A double-blinded, randomized, sham-controlled trial.

Background: Auricular acupuncture (AA) has been widely used in overweight and obesity management due to its safety and effectiveness. The combination of other acupuncture therapies with thread-embedding acupuncture (TEA) has shown enhanced effects. However, there is a lack of evidence regarding AA plus TEA for overweight and obesity. This study was conducted to address this question. Methods: A randomized placebo-controlled trial was conducted involving 66 overweight or obese participants, divided into two groups: 33 received AA plus TEA, and 33 received AA plus sham TEA over eight weeks. The primary outcome was body weight (BW) reduction. Secondary outcomes included changes in body mass index (BMI) and waist circumference (WC), hip circumference (HC), waist-hip ratio (WHR), food cravings questionnaire-trait-reduced (FCQ-Tr) and food craving visual analog scale (VAS) scores. Safety outcomes were adverse events (AEs). Results: After eight weeks, BW decreased by a mean (SD) of -4.45 (1.29) kg and -2.05 (1.33) kg in the AA plus TEA and AA plus sham TEA groups, respectively (MD [95 % CI]: 2.40 [1.75; 3.05]). BMI, WC, WHR, and food craving VAS score decreased significantly more in the AA plus TEA group than in the AA plus sham TEA group. No significant differences were found in FCQ-Tr and HC between groups. Seven AEs were recorded that were mild and resolved without treatment. Conclusion: The addition of TEA to AA is a safe and effective management of overweight and obesity. Further studies should incorporate dietary and lifestyle modifications and follow-up after the intervention to assess long-term effectiveness. Trial registration: The study protocol had been registered on ClinicalTrials.gov (NCT06091761).

Auricular Acupuncture Prior to Menstruation Can Reduce Primary Dysmenorrhea: A Randomized Controlled Trial.

Objective: Primary dysmenorrhea is a common condition that impacts quality of life significantly. Auricular therapies have shown promise for treating primary dysmenorrhea, but there is a lack of evidence specifically for auricular acupuncture (AA). This study evaluated the safety and efficacy of AA for managing primary dysmenorrhea. Materials and Methods: A randomized, double-blinded controlled trial was conducted on 90 females with primary dysmenorrhea: an AA group; n = 45) and a sham-AA (SA) group; n = 45. Specific ear acupoints (i.e., Uterus, Endocrine, Shenmen, Subcortex, Liver, and Kidney) were used for the intervention, which was 1 or 2 days prior to the expected menstruation onset. Outcomes were visual analogue scale (VAS) scores, ibuprofen needs, and adverse events (AEs). Results: The AA group had significantly lower VAS scores, compared to the SA group at menstruation onset and for up to 12 hours (mean differences [MDs] and 95% confidence intervals [CIs]: -1.08 [-1.96, -0.21] and -1.17 [-2.16, -0.18], respectively). Both groups had reductions in pain levels, compared to the prior menstrual cycle; the AA group had a significantly greater improvement. The AA group needed fewer ibuprofen tablets (MD: -0.28; 95% CI: -0.58, 0.00]). AEs were mild pain and irritation at insertion sites, all resolved spontaneously with no lasting effects. Conclusions: AA is safe. It may be effective for managing primary dysmenorrhea. Further studies are warranted on AA's effectiveness in diverse populations and extended times.

Exploring organisational readiness to implement a preventive intervention in Australian general practice for overweight and obese patients: key learnings from the HeLP-GP trial.

BACKGROUND: The HeLP-GP trial aimed to increase the capacity of practice nurses to deliver weight management to overweight and obese patients through an intervention comprising a health check, a lifestyle app and/or telephone coaching. This paper describes implementation through the lens of organisational readiness with emphasis on the role of the practice nurse. METHODS: Routinely collected mixed method research data including practice surveys, field notes, and diaries and process data were mapped against the domains: motivation to implement, general capacity and intervention-specific capacity. RESULTS: Organisational readiness varied considerably, particularly the domain of intervention-specific capacity. Practice nurse turnover negatively impacted the implementation, affecting half of the practices. We observed a general lack of practice-based support for intervention delivery, and varying levels of interest, skill and confidence in delivering the intervention. Nurses struggled to complete the research and intervention tasks in a timely way. Conducting risk assessments and referring to coaching were generally not problematic; however, we noted lower confidence levels with the lifestyle app and instructing patients to use it. CONCLUSIONS: We found a lack of general 'readiness' inherent in the nursing role, particularly related to their capacity to complete intervention tasks and practice-level support to implement the intervention. For nurses in general practice to fulfil their potential in supporting patients to reduce risk and adopt healthier life choices, our study indicates that more could be done to improve their workforce positioning and remuneration, which may, in turn, improve continuity of care, retention and individual motivation.