The cardioprotective effects of histone deacetylase (HDAC) inhibitors (HDIs) are at odds with the deleterious effects of HDAC depletion. Here, we use HDAC3 as a prototype HDAC to address this contradiction. We show that adult-onset cardiac-specific depletion of HDAC3 in mice causes cardiac hypertrophy and contractile dysfunction on a high-fat diet (HFD), excluding developmental disruption as a major reason for the contradiction. Genetically abolishing HDAC3 enzymatic activity without affecting its protein level does not cause cardiac dysfunction on HFD. HDAC3 depletion causes robust downregulation of lipid oxidation/bioenergetic genes and upregulation of antioxidant/anti-apoptotic genes. In contrast, HDAC3 enzyme activity abolishment causes much milder changes in far fewer genes. The abnormal gene expression is cardiomyocyte-autonomous and can be rescued by an enzyme-dead HDAC3 mutant but not by an HDAC3 mutant (Δ33-70) that lacks interaction with the nuclear-envelope protein lamina-associated polypeptide 2β (LAP2β). Tethering LAP2β to the HDAC3 Δ33-70 mutant restored its ability to rescue gene expression. Finally, HDAC3 depletion, not loss of HDAC3 enzymatic activity, exacerbates cardiac contractile functions upon aortic constriction. These results suggest that the cardiac function of HDAC3 in adults is not attributable to its enzyme activity, which has implications for understanding the cardioprotective effects of HDIs.

Hermansky-Pudlak syndrome (HPS), both alone and in conjunction with pulmonary fibrosis (HPS-PF), is a rare, genetically heterogeneous, autosomal recessive disorder that affects multiple organs, including the lungs. In cases of HPS-PF, pulmonary fibrosis is preceded by local inflammation. We present a case of HPS-PF that exhibited histological evidence of extracellular traps (ETs) ensnaring macrophages, leading to cell death in a process known as ETosis. To our knowledge, ETosis has not been previously reported in the HPS-PF population and may represent a mechanism by which pulmonary fibrosis develops in these patients. Further research is needed to explore the potential connection between ETosis and HPS-PF, as this understanding could offer insights into the disease mechanism and pave the way for the development of novel treatment modalities.

Hermansky-Pudlak syndrome (HPS), both alone and in conjunction with pulmonary fibrosis (HPS-PF), is a rare, genetically heterogeneous, autosomal recessive disorder that affects multiple organs, including the lungs. In cases of HPS-PF, pulmonary fibrosis is preceded by local inflammation. We present a case of HPS-PF that exhibited histological evidence of extracellular traps (ETs) ensnaring macrophages, leading to cell death in a process known as ETosis. To our knowledge, ETosis has not been previously reported in the HPS-PF population and may represent a mechanism by which pulmonary fibrosis develops in these patients. Further research is needed to explore the potential connection between ETosis and HPS-PF, as this understanding could offer insights into the disease mechanism and pave the way for the development of novel treatment modalities.

Hermansky-Pudlak syndrome (HPS), both alone and in conjunction with pulmonary fibrosis (HPS-PF), is a rare, genetically heterogeneous, autosomal recessive disorder that affects multiple organs, including the lungs. In cases of HPS-PF, pulmonary fibrosis is preceded by local inflammation. We present a case of HPS-PF that exhibited histological evidence of extracellular traps (ETs) ensnaring macrophages, leading to cell death in a process known as ETosis. To our knowledge, ETosis has not been previously reported in the HPS-PF population and may represent a mechanism by which pulmonary fibrosis develops in these patients. Further research is needed to explore the potential connection between ETosis and HPS-PF, as this understanding could offer insights into the disease mechanism and pave the way for the development of novel treatment modalities.

Objectives: This study aimed to present the Asia-Pacific consensus on long-term and sequential therapy for osteoporosis, offering evidence-based recommendations for the effective management of this chronic condition.The primary focus is on achieving optimal fracture prevention through a comprehensive, individualized approach. Methods: A panel of experts convened to develop consensus statements by synthesizing the current literature and leveraging clinical expertise. The review encompassed long-term anti-osteoporosis medication goals, first-line treatments for individuals at very high fracture risk, and the strategic integration of anabolic and anti resorptive agents in sequential therapy approaches. Results: The panelists reached a consensus on 12 statements. Key recommendations included advocating for anabolic agents as the first-line treatment for individuals at very high fracture risk and transitioning to anti resorptive agents following the completion of anabolic therapy. Anabolic therapy remains an option for in dividuals experiencing new fractures or persistent high fracture risk despite antiresorptive treatment. In cases of inadequate response, the consensus recommended considering a switch to more potent medications. The consensus also addressed the management of medication-related complications, proposing alternatives instead of discontinuation of treatment. Conclusions This consensus provides a comprehensive, cost-effective strategy for fracture prevention with an emphasis on shared decision-making and the incorporation of country-specific case management systems, such as fracture liaison services. It serves as a valuable guide for healthcare professionals in the Asia-Pacific region, contributing to the ongoing evolution of osteoporosis management.

Background: The initiation of sodium-glucose cotransporter-2 inhibitors (SGLT2i) typically leads to a reversible initial dip in estimated glomerular filtration rate (eGFR). The implications of this phenomenon on clinical outcomes are not well-defined. Methods: We searched MEDLINE, Embase, and Cochrane Library from inception to March 23, 2023 to identify randomized controlled trials and cohort studies comparing kidney and cardiovascular outcomes in patients with and without initial eGFR dip after initiating SGLT2i. Pooled estimates were calculated using random-effect meta-analysis. Results: We included seven studies in our analysis, which revealed that an initial eGFR dip following the initiation of SGLT2i was associated with less annual eGFR decline (mean difference, 0.64; 95% confidence interval [CI], 0.437 to 0.843) regardless of baseline eGFR. The risk of major adverse kidney events was similar between the non-dipping and dipping groups but reduced in patients with a ≤10% eGFR dip (hazard ratio [HR], 0.915; 95% CI, 0.865 to 0.967). No significant differences were observed in the composite of hospitalized heart failure and cardiovascular death (HR, 0.824; 95% CI, 0.633 to 1.074), hospitalized heart failure (HR, 1.059; 95% CI, 0.574 to 1.952), or all-cause mortality (HR, 0.83; 95% CI, 0.589 to 1.170). The risk of serious adverse events (AEs), discontinuation of SGLT2i due to AEs, kidney-related AEs, and volume depletion were similar between the two groups. Patients with >10% eGFR dip had increased risk of hyperkalemia compared to the non-dipping group. Conclusion Initial eGFR dip after initiating SGLT2i might be associated with less annual eGFR decline. There were no significant disparities in the risks of adverse cardiovascular outcomes between the dipping and non-dipping groups.

Objective: The aim of this study was to investigate the efficacy of endoscopically visualized radiofrequency for treating sacroiliac joint pain. Methods: The study protocol was preregistered on INPLASY (INPLASY202450011). A systematic search was carried out across multiple databases, including PubMed, Embase, Cochrane CENTRAL, and Web of Science, from their inception until May 6, 2024. Peer-reviewed studies on human participants with low back pain diagnosed with sacroiliac joint pain and treated with endoscopically visualized radiofrequency ablation (RFA) were included. The study focused on evaluating changes in the visual analogue scale (VAS) and Oswestry Disability Index (ODI) from before the commencement of endoscopically visualized radiofrequency to postoperation. The quantitative syntheses employed a random-effects model, with effect sizes reported using the mean difference. Subgroup analyses were conducted based on 6-month and 12-month postoperative time points. Results: Four studies were ultimately included in this meta-analysis. Three of the studies were case series, while one was a retrospective cohort study. The mean difference of VAS scores between the preoperative and 6-month and 12-month postoperative assessments was -5.60 and -5.96, respectively. The mean difference of the ODI between preoperative and 6-month and 12-month postoperative assessments was -21.03 and -23.67, respectively. A subgroup analysis of both outcome measurement indices at the 2 follow-up time points did not reveal any statistically significant differences. Conclusion Endoscopically visualized RFA demonstrates potential as a treatment modality for sacroiliac joint pain; however, there is currently insufficient evidence to substantiate its long-term efficacy.

Background/Aims: Chronic hepatitis B (CHB) and fatty liver (FL) often co-exist, but natural history data of this dual condition (CHB-FL) are sparse. Via a systematic review, conventional meta-analysis (MA) and individual patient-level data MA (IPDMA), we compared liver-related outcomes and mortality between CHB-FL and CHB-no FL patients. Methods: We searched 4 databases from inception to December 2021 and pooled study-level estimates using a random- effects model for conventional MA. For IPDMA, we evaluated outcomes after balancing the two study groups with inverse probability treatment weighting (IPTW) on age, sex, cirrhosis, diabetes, ALT, HBeAg, HBV DNA, and antiviral treatment. Results: We screened 2,157 articles and included 19 eligible studies (17,955 patients: 11,908 CHB-no FL; 6,047 CHB-FL) in conventional MA, which found severe heterogeneity (I2=88–95%) and no significant differences in HCC, cirrhosis, mortality, or HBsAg seroclearance incidence (P=0.27–0.93). IPDMA included 13,262 patients: 8,625 CHB-no FL and 4,637 CHB-FL patients who differed in several characteristics. The IPTW cohort included 6,955 CHB-no FL and 3,346 CHB-FL well-matched patients. CHB-FL patients (vs. CHB-no FL) had significantly lower HCC, cirrhosis, mortality and higher HBsAg seroclearance incidence (all p≤0.002), with consistent results in subgroups. CHB-FL diagnosed by liver biopsy had a higher 10-year cumulative HCC incidence than CHB-FL diagnosed with non-invasive methods (63.6% vs. 4.3%, p<0.0001). Conclusions IPDMA data with well-matched CHB patient groups showed that FL (vs. no FL) was associated with significantly lower HCC, cirrhosis, and mortality risk and higher HBsAg seroclearance probability.

Detection of early drug abuse has driven the use of mass spectrometry in clinical laboratories across North America. Mass spectrometry-based assays have been increasingly implemented in various clinical disciplines for their advantages in high analytical sensitivity, specificity and multiplexing capacity. Mass spectrometry is now routinely used for the clinical analysis of small molecule compounds, peptides, proteins, clinical toxicology and microbiology. Although more FDA-approved platforms and reagents need to be commercially available, there is no doubt that mass spectrometry technology has demonstrated rich clinical applications.

Aims: The search for new antibiotics is an ongoing effort and has expanded to pristine niche areas in the Antarctic in recent years due to the emergence of multi-drug resistant pathogens that outpaced the discovery of new antibiotics. We have recently isolated two new actinomycetes strains, INACH3013a and INACH3013b, which displayed antimicrobial properties from soil samples collected from Ardley Island, Antarctica. Hence, an investigation was carried out to identify them and to characterise the antimicrobial compounds produced. Methodology and results: Strains, INACH3013a and INACH3013b were identified based on their 16S rDNA sequence alignment to those in the GenBank. The results showed that strain INACH3013a was closest to Streptomyces spp. while strain INACH3013b was closest to Streptomyces corallincola and Streptomyces bullii. The extracellular compounds they produced were extracted using various solvents and the extracted compounds were tested against the test pathogens. The dichloromethane extracts from strains, INACH3013a and INACH3013b inhibited mainly Gram-positive pathogens that include Listeria monocytogenes, Staphylococcus aureus, Staphylococcus haemolyticus, Staphylococcus equorum, Bacillus cereus K3 and Enterococcus faecalis while extracts from strain INACH3013b also inhibited a Gram-negative pathogen, Klebsiella pneumonia 14x. Predominantly non-polar constituents seem responsible for antibacterial effects, with dichloromethane extracts proving most efficacious, followed by chloroform and ethyl acetate. Conclusion, significance and impact of study The research highlights the potential of Streptomyces spp. INACH3013a and INACH3013b as a source of potential novel antibiotics. This research explores Antarctic Streptomyces strains' antimicrobial capabilities, enabling the potential for the discovery of novel antibiotics and revealing how these compounds may have helped them to compete and survive in nutrient-deficient Antarctic niches.