Chloroquine decreases cardiac fibrosis and improves cardiac function in a mouse model of Duchenne muscular dystrophy

by Takuya Hirata, Shiro Baba, Kentaro Akagi, Koichi Matsuda, Katsutsugu Umeda, Souichi Adachi, Toshio Heike, Junko Takita

Background

Duchenne muscular dystrophy (DMD), a severe degenerative skeletal and cardiac muscle disease, has a poor prognosis, and no curative treatments are available. Because decreased autophagy has been reported to contribute to skeletal muscle degeneration, therapies targeting autophagy are expected to improve skeletal muscle hypofunction. However, the role of this regulatory mechanism has not been evaluated clearly in DMD cardiomyocytes.

Methods

In this present study, we evaluated myocardial fibrosis and its mechanism in mdx mice, a model of DMD, and also evaluated changes in cardiac function.

Results

As assessed by LC3 immunohistochemistry, a small number of autophagosomes were detected in cardiomyocytes of both mdx mice and control wild-type (WT) mice. The number of autophagosomes was significantly enhanced by 4 weeks of isoproterenol-induced cardiac stress in cardiomyocytes of mdx but not WT mice. Simultaneously, isoproterenol increased cardiomyocyte fibrosis in mdx but not WT mice. Administration of chloroquine significantly decreased cardiomyocyte fibrosis in mdx mice, even after isoproterenol treatment. Left ventricle size and function were evaluated by echocardiography. Left ventricular contraction was decreased in mdx mice after isoproterenol treatment compared with control mice, which was alleviated by chloroquine administration.

Conclusions

Heart failure in DMD patients is possibly treated with chloroquine, and the mechanism probably involves chloroquine’s anti-inflammatory effects.

Exploring knowledge, perceptions, and practices of antimicrobials, and their resistance among medicine dispensers and community members in Kavrepalanchok District of Nepal

by Sabina Marasini, Sudim Sharma, Anjali Joshi, Surakshya Kunwar, Roshan Kumar Mahato, Archana Shrestha, Biraj Karmacharya

Background

Inappropriate use of antimicrobials is a global public health issue, particularly in developing countries, including Nepal, where over-the-counter sales and self-medication of antimicrobials are common.

Objectives

To explore knowledge, perceptions, and practices of antimicrobials and their resistance among medicine dispensers and community members in Nepal.

Methods

The study was conducted in three rural and five urban municipalities of the Kavrepalanchok district from May 2021 to August 2021. Data were collected using two qualitative approaches: In-Depth Interviews (IDIs) and Focus Group Discussions (FGDs). Data were analyzed using thematic analysis that combined deductive and inductive approaches to identify codes under pre-specified themes.

Results

A total of 16 In-depth interviews with medicine dispensers and 3 focus group discussions with community members were conducted. Knowledge regarding antimicrobial resistance varied among dispensers. Those with a prior educational background in pharmacy often had good knowledge about the causes and consequences of antimicrobial resistance. Meanwhile, consumers were less aware of antimicrobial resistance. Community members perceived antimicrobials as effective medicines but not long-term solution for treating diseases. They reported that dispensing without a prescription was common and that both consumers and dispensers were responsible for the inappropriate use of antimicrobials. On the contrary, several dispensers said that self-medication was common among the consumers, especially among more educated groups. The medicine dispensers and consumers expressed concerns about the weak enforcement of policies regarding pharmacy drug use and dispensing practices.

Conclusion

Promoting and strengthening the appropriate use of antimicrobials among medicine dispensers and community members is crucial. Bold policies and collective implementation of regulations could help combat antimicrobial resistance.

Dislodgement resistance and structural changes of tricalcium silicate-based cements after exposure to different chelating agents

by Özgür İlke Ulusoy, Nidambur Vasudev Ballal, Rajkumar Narkedamalli, Nuran Ulusoy, Krishna Prasad Shetty, Alexander Maniangat Luke

This study aimed to evaluate the dislodgement resistance and structural changes of different mineral trioxide aggregate cements (MTA) like Pro-Root MTA, Ortho MTA, and Retro MTA after exposure to sodium hypochlorite (NaOCl), NaOCl-Ethylenediaminetetraacetic acid (EDTA), 1-hydroxyethylidene-1, 1-bisphosphonate (Dual Rinse HEDP), and NaOCl-Maleic acid (MA). The root canal spaces of 150 dentine slices were obturated using tricalcium silicate cements and divided into 3 groups (n = 50): Group1: ProRoot MTA, Group2: Retro MTA, and Group3: Ortho MTA. The samples in each group were further subdivided into four experimental (n = 10) and one control groups (n = 10): 2.5% NaOCl-17% EDTA, Dual Rinse HEDP, 2.5% NaOCl-7% Maleic acid, 2.5% NaOCl, distilled water (control). The dislodgement resistance and structural changes of cements were measured. Use of DR HEDP resulted in higher dislodgement resistance compared to17% EDTA and 7% MA in the samples obturated with Ortho MTA and Pro-Root MTA (p

Persistence of gut dysbiosis in individuals with anorexia nervosa

by Yukiko Morisaki, Noriyuki Miyata, Megumi Nakashima, Tomokazu Hata, Shu Takakura, Kazufumi Yoshihara, Takafumi Suematsu, Koji Nomoto, Kouji Miyazaki, Hirokazu Tsuji, Nobuyuki Sudo

Recent evidence suggests a crucial role of the gut microbiota in the pathogenesis of anorexia nervosa (AN). In this study, we carried out a series of multiple analyses of the gut microbiota of hospitalized individuals with AN over three months using 16S or 23S rRNA-targeted reverse transcription–quantitative polymerase chain reaction (PCR) technology (YIF-SCAN^®), which is highly sensitive and enables the precise quantification of viable microorganisms. Despite the weight gain and improvements in psychological features observed during treatment, individuals with AN exhibited persistent gut microbial dysbiosis over the three-month duration. Principal component analysis further underscored the distinct microbial profile of individuals with AN, compared with that of age-matched healthy women at all time points. Regarding the kinetics of bacterial detection, the detection rate of Lactiplantibacillus spp. significantly increased after inpatient treatment. Additionally, the elevation in the Bifidobacterium counts during inpatient treatment was significantly correlated with the subsequent body weight gain after one year. Collectively, these findings suggest that gut dysbiosis in individuals with AN may not be easily restored solely through weight gain, highlighting the potential of therapeutic interventions targeting microbiota via dietary modifications or live biotherapeutics.

Differentiating attack-defense performance for starting and bench players during the Tokyo Olympics men’s basketball competition

by Wenping Sun, ChenSoon Chee, LianYee Kok, FongPeng Lim, Shamsulariffin Samsudin

This study aimed to explore the differences in attack-defense performance between the top and bottom teams for starting and bench players during the Tokyo Olympics men’s basketball competition, to determine the relationship between the attack-defense performance of starting and bench players and the final competition rankings, as well as with each performance indicator. The rank-sum ratio (RSR) comprehensive evaluation was employed to describe the attack-defense performance of starting and bench players. Additionally, an independent sample t-test, Spearman Rho Correlation, and Pearson Correlation were conducted to test the differences and relationships between the various variables at a 0.05 level of significance, respectively. The results indicated that the top four teams showed significant differences in the attack-defense performance of their starting players compared to the bottom four teams (p = 0.021), mainly in terms of 3-point shooting percentage (p = 0.042) and free throw shooting percentage (p = 0.044). Besides that, the attack-defense ranks of both starting players (p = 0.004, r = 0.757) and bench players (p = 0.020, r = 0.658) had a significant correlation with the final rankings. Points per game, 2-point field goal percentage, and assists had a statistically significant (pr

Effects of high-intensity functional training on physical fitness and sport-specific performance among the athletes: A systematic review with meta-analysis

by Xinzhi Wang, Kim Geok Soh, Shamsulariffin Samsudin, Nuannuan Deng, Xutao Liu, Yue Zhao, Saddam Akbar

Objective

This study aims to meta-analyze the impact of high-intensity functional training on athletes’ physical fitness and sport-specific performance.

Methods

A systematic search was conducted in five well-known academic databases (PubMed, Scopus, Web of Science, EBSCOhost, and the Cochrane Library) up to July 1, 2023. The literature screening criteria included: (1) studies involving healthy athletes, (2) a HIFT program, (3) an assessment of outcomes related to athletes’ physical fitness or sport-specific performance, and (4) the inclusion of randomized controlled trials. The Physical Therapy Evidence Database (PEDro) scale was used to evaluate the quality of studies included in the meta-analysis.

Results

13 medium- and high-quality studies met the inclusion criteria for the systematic review, involving 478 athletes aged between 10 and 24.5 years. The training showed a small to large effect size (ES = 0.414–3.351; all p Conclusion

High-intensity functional training effectively improves athletes’ muscle strength, power, flexibility, and sport-specific performance but has no significant impact on endurance and agility. Future research is needed to explore the impact of high-intensity functional training on athletes’ speed, balance, and technical and tactical performance parameters.

Cumulative violence exposures among men who have sex with men living with HIV in India: Psychosocial correlates of HIV care continuum outcomes

by Bushra Sabri, Chakra Budhathoki, Allison M. McFall, Shruti H. Mehta, David D. Celentano, Sunil S. Solomon, Aylur K. Srikrishnan, Santhanam Anand, Canjeevaram K. Vasudevan, Gregory M. Lucas

Lifetime exposures to violence among men who have sex with men (MSM) are associated with multiple psychosocial health risks and can affect engagement and outcomes of HIV treatment. This study a) explored relationships between levels of exposures to violence and HIV care continuum outcomes among MSM living with HIV in India, and b) identified psychosocial correlates of HIV care continuum outcomes among MSM living with HIV and those with lifetime cumulative exposures to violence (CVE). CVE referred to exposures to violence in both childhood and adulthood. This cross-sectional analysis used survey data collected between August 2016 and May 2017 from 1763 men who have sex with men living with HIV across 10 cities in India, using respondent-driven sampling. We found that higher levels of violence exposure were significantly associated with lower awareness of HIV positive status, and lower likelihood of initiating antiretroviral therapy. Compared with MSM living with HIV that had no CVE, those with CVE were more likely to report perpetration of interpersonal violence, alcohol misuse, depressive symptoms, and HIV transmission risk behaviors and to have two to four co-occurring psychosocial problems. In multivariable analysis with the subset of MSM with CVE, psychosocial correlates significantly associated with at least one HIV care continuum outcome were HIV transmission risk behaviors, perpetration of interpersonal violence, depression, and alcohol misuse. The findings highlight the need for integrating care for lifetime violence exposures and associated behavioral problems in HIV care settings for men who have sex with men living with HIV in India.

Molecular characterization of <i>G6PD</i> mutations identifies new mutations and a high frequency of intronic variants in Thai females

by Kamonwan Chamchoy, Sirapapha Sudsumrit, Jutamas Wongwigkan, Songsak Petmitr, Duantida Songdej, Emily R. Adams, Thomas Edwards, Ubolsree Leartsakulpanich, Usa Boonyuen

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is an X-linked enzymopathy caused by mutations in the G6PD gene. A medical concern associated with G6PD deficiency is acute hemolytic anemia induced by certain foods, drugs, and infections. Although phenotypic tests can correctly identify hemizygous males, as well as homozygous and compound heterozygous females, heterozygous females with a wide range of G6PD activity may be misclassified as normal. This study aimed to develop multiplex high-resolution melting (HRM) analyses to enable the accurate detection of G6PD mutations, especially among females with heterozygous deficiency. Multiplex HRM assays were developed to detect six G6PD variants, i.e., G6PD Gaohe (c.95A>G), G6PD Chinese-4 (c.392G>T), G6PD Mahidol (c.487G>A), G6PD Viangchan (c.871G>A), G6PD Chinese-5 (c.1024C>T), and G6PD Union (c.1360C>T) in two reactions. The assays were validated and then applied to genotype G6PD mutations in 248 Thai females. The sensitivity of the HRM assays developed was 100% [95% confidence interval (CI): 94.40%–100%] with a specificity of 100% (95% CI: 88.78%–100%) for detecting these six mutations. The prevalence of G6PD deficiency was estimated as 3.63% (9/248) for G6PD deficiency and 31.05% (77/248) for intermediate deficiency by phenotypic assay. The developed HRM assays identified three participants with normal enzyme activity as heterozygous for G6PD Viangchan. Interestingly, a deletion in intron 5 nucleotide position 637/638 (c.486-34delT) was also detected by the developed HRM assays. G6PD genotyping revealed a total of 12 G6PD genotypes, with a high prevalence of intronic variants. Our results suggested that HRM analysis-based genotyping is a simple and reliable approach for detecting G6PD mutations, and could be used to prevent the misdiagnosis of heterozygous females by phenotypic assay. This study also sheds light on the possibility of overlooking intronic variants, which could affect G6PD expression and contribute to enzyme deficiency.