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Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia.

Abstract Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia.

Abstract Background In Myanmar, ongoing conflict since the 2021 military coup d’etat has been characterized by targeted violence against health workers (HWs), particularly those participating in the pro-democracy movement. Existing knowledge about the challenges faced by health workers in Myanmar is scant, including their perspectives on mitigating their suffering and the broader impact on community health. This knowledge gap prompted our study to assess the extent of the violence, its impact on the workers and the community, and identify resource priorities. Methods This qualitative study employed purposive and snowball sampling to recruit health workers affiliated with the Civil Disobedience Movement (CDM). We interviewed 24 HWs in Myanmar between July and December 2022, predominantly physicians and nurses. We used a semi-structured interview guide and conducted interviews remotely due to the security situation. We adopted content analysis to understand participation in the CDM movement, experiences of violence, personal and professional impacts, the sequelae to community health, how HWs responded as well as their ongoing needs. Results Thematic content analysis revealed that violence was both individually targeted and widespread. Health workers faced professional, financial, and personal impacts as a result. The health system as a whole has been severely diminished. Health workers have had to adapt to continue to provide care, for example some fled to rural areas and worked clandestinely, exchanging their services for food and shelter. In those settings, they continued to face insecurity from airstrikes and arrests. Health workers have also experienced moral distress and burden due to their resistance and protest against the regime. Conclusion The coup and ensuing violence severely disrupted the healthcare system, resulting in shortages of supplies, reduced quality of care, and exacerbated challenges during the COVID-19 pandemic. Despite facing significant hardships, HWs remained resilient, engaging in resistance efforts within the CDM and seeking support from local communities and international organizations. They expressed a need for increased awareness, financial assistance, and concrete support for the health system to address the crisis.

Lack of maternal milk commonly leads to Asian elephant calves’ death in captivity. Currently, available supplements seem inefficient. Hence, we aimed at characterizing the composition of Asian elephant milk to provide information on calves’ nutritional needs. Seventy milk samples from 22 Asian elephants living in semi-captivity in their natural environment in Myanmar were collected. Samples were analysed through various techniques including liquid chromatography tandem mass spectrometry, gas chromatography-flame ionization detector, and bicinchoninic acid assay to determine total protein content and various metabolites. Associations with lactation stage (months postpartum) were investigated through repeated measure mixed models. We identified 160 compounds: 22 amino acids, 12 organic acids of the tricarboxylic acid cycle, 27 fatty acids, 15 acyl-carnitines and 84 phospholipids. The milk contained substantial amounts of free glutamate (median: 1727.9, interquartile range (IQR): 1278.4 µmol l−1) and free glycine (2541.7, IQR: 1704.1 µmol l−1). The fatty acid profile was mostly constituted by saturated fatty acids, particularly capric acid (40.1, IQR: 67.3 g l−1). Milk samples also contained high amounts of carnitines, phospholipids and organic acids. The wide array of metabolites identified and quantified, some of which present high concentrations in the milk from this species as opposed to other species, suggests underpinning physiological functions that might be crucial for the survival of Asian elephant calves.

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Chimeric antigen receptor T cell (CAR-T) therapies are Food and Drug Administration (FDA)-approved for patients with triple refractory multiple myeloma (MM). Real-world access to CAR-T therapy remains challenging owing to supply chain limitations impacting manufacturing. The goal of this study was to evaluate the extent of this issue and how major centers are handling the challenges of CAR-T manufacturing slot allocation. MM CAR-T physician leaders at each CAR-T treatment center across the United States were surveyed. We received responses from 17 of 20 centers. A median of 1 slot is allocated per month per center, and the median number of patients per center on the waitlist since the FDAs approval of idecabtagene vicleucel is 20 (range, 5 to 100). As a result, patients remain on the waitlist for a median of 6 months (range, 2 to 8 months) prior to leukapheresis. For patient selection, all centers reported using a committee of experienced CAR-T physicians to ensure consistency. To ensure transparency, 15 centers make selection criteria, selection timelines, and priority scores readily available for CAR-T providers. Centers also reported using ethical values for selection: (1) equal treatment: time spent on waiting list (n = 12); (2) priority to the worst-off: limited therapeutic options (n = 14), MM burden (n = 11), high Hematopoietic Cell Transplantation Comorbidity Index (n = 5); (3) maximize benefit: most likely to complete apheresis (n = 13) or infusion (n = 13) or to achieve response (n = 8); and (4) social value: younger patients (n = 3). Maximizing benefit was considered the most important criterion by 10 centers. This study is the first attempt to evaluate existing issues with CAR-T access for patients with MM and the variability and challenges in patient selection. Integrating ethical resource allocation strategies, similar to those described here, into formal institutional policies would help streamline access to CAR-T therapy and protect the needs of both current and future patients and physicians.

Sunflower (Helianthus annuus L.) is a widely cultivated, fast-growing crop known for its seeds and oil, with substantial ecological and economic importance globally. However, it faces challenges from leaf diseases caused by Alternaria species, which threaten its yield. Three small-spored Alternaria species were isolated from leaf spot and blight symptoms on sunflower in Myanmar. All the species were determined based on morphological characterization and a multi-locus phylogenetic assessment of seven genes, including the internal transcribed spacer of rDNA region (ITS), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), RNA polymerase second largest subunit (RPB2), translation elongation factor 1-α (TEF1), Alternaria major allergen gene (Alt a 1), endopolygalacturonase gene (EndoPG), and an anonymous gene region (OPA10-2). The results introduced two new Alternaria species, A. myanmarensis sp. nov. and A. yamethinensis sp. nov., and a known species of A. burnsii, firstly reported from sunflower.

Abstract Background To fight the current coronavirus disease (COVID-19) pandemic, many countries have implemented various mitigation measures to contain the spread of the disease. By engaging with health service providers, the community’s participation in adherence to preventive measures is certainly required in the implementation of COVID-19 mitigation strategies. Therefore, this study aimed to assess the level of adherence to COVID-19 preventive measures and its associated factors among the residents, Yangon Region, Myanmar. Methods A community-based cross-sectional study was carried out among 636 residents in Yangon Region, Myanmar, from October to December 2021. A multistage non-probability sampling method, purposively selected for three townships in Yangon Region and convenience sampling for 212 participants from each township, was applied and the data were collected by face-to-face interviews using structured and pretested questionnaires. Data were entered, coded, and analyzed using IBM SPSS version 25.0. Simple and multiple logistic regression analysis were performed to identify the significant variables of adherence to COVID-19 preventive measures. Results As a level of adherence to COVID-19 preventive measures, the proportion of residents who had good adherence was 39.3% (95% CI 35.5–43.2%), moderate adherence was 37.6% (95% CI 33.8–41.5%), and poor adherence was 23.1% (95% CI 19.9–26.6%). The age group of 31–40 years (AOR: 3.13, 95% CI 1.62–6.05), 30 years and younger (AOR: 3.22, 95% CI 1.75–5.92), Burmese ethnicity (AOR: 2.52, 95% CI 1.44–4.39), own business (AOR: 3.19, 95% CI 1.15–8.87), high school education level and below (AOR: 1.64, 95% CI 1.02–2.69), less than 280.90 USD of monthly family income (AOR: 1.51, 95% CI 1.01–2.29), low knowledge about COVID-19 (AOR: 1.90, 95% CI 1.26–2.88) were significantly associated with poor adherence to COVID-19 preventive measures. Conclusions In this study, nearly one-fourth of the residents were experiencing poor adherence to COVID-19 preventive measures. Therefore, building up the risk communication through the community using widely used mainstream media, the continuation of disease surveillance and announcement of updated information or advice for the public to increase awareness towards COVID-19, and enforcement to follow the recommended directions and regulations of health institutions are vital to consider for improving the adherence to preventive measures against COVID-19 among the residents.

Rare diseases affect almost 500 million people globally, predominantly impacting children and often leading to significantly impaired quality of life and high treatment costs. While significant contributions have been made to develop effective treatments for those with rare diseases, more rapid drug discovery strategies are needed. Therapeutic antisense oligonucleotides can modulate target gene expression with high specificity through various mechanisms determined by base sequences and chemical modifications; and have shown efficacy in clinical trials for a few rare neurological conditions. Therefore, this review will focus on the applications of antisense oligonucleotides, in particular splice-switching antisense oligomers as promising therapeutics for rare neurological diseases, with key examples of Duchenne muscular dystrophy and spinal muscular atrophy. Challenges and future perspectives in developing antisense therapeutics for rare conditions including target discovery, antisense chemical modifications, animal models for therapeutic validations, and clinical trial designs will also be briefly discussed.

We report on a patient with ciltacabtagene autoleucel-induced movement and neurocognitive toxicity, which was refractory to immunosuppression but responsive to combination dopaminergic therapy (carbidopa/levodopa, ropinirole, amantadine). Response was seen upon both initial treatment and rechallenge after unintended withdrawal. This is the first report of a successful symptomatic treatment of this well-described neurotoxic syndrome.

Down syndrome is a genetic-based disorder that results from the triplication of chromosome 21, leading to an overexpression of many triplicated genes, including the gene encoding Dual-Specificity Tyrosine Phosphorylation-Regulated Kinase 1A (DYRK1A). This protein has been observed to regulate numerous cellular processes, including cell proliferation, cell functioning, differentiation, and apoptosis. Consequently, an overexpression of DYRK1A has been reported to result in cognitive impairment, a key phenotype of individuals with Down syndrome. Therefore, downregulating DYRK1A has been explored as a potential therapeutic strategy for Down syndrome, with promising results observed from in vivo mouse models and human clinical trials that administered epigallocatechin gallate. Current DYRK1A inhibitors target the protein function directly, which tends to exhibit low specificity and selectivity, making them unfeasible for clinical or research purposes. On the other hand, antisense oligonucleotides (ASOs) offer a more selective therapeutic strategy to downregulate DYRK1A expression at the gene transcript level. Advances in ASO research have led to the discovery of numerous chemical modifications that increase ASO potency, specificity, and stability. Recently, several ASOs have been approved by the U.S. Food and Drug Administration to address neuromuscular and neurological conditions, laying the foundation for future ASO therapeutics. The limitations of ASOs, including their high production cost and difficulty delivering to target tissues can be overcome by further advances in ASO design. DYRK1A targeted ASOs could be a viable therapeutic approach to improve the quality of life for individuals with Down syndrome and their families.

Abstract Background Usually, pectus bars are removed 3 years after the Nuss procedure in patients with pectus excavatum. However, the optimal timing for postoperative pectus bar removal remains undefined. Our study investigated the effects of delayed pectus bar removal after Nuss repairs. Methods Retrospective data were collected on patients who underwent Nuss procedures for pectus excavatum and had their bars removed from August 2014 to December 2020. Patients with correction periods > 3 years were divided into group A ( 3 years. The average correction duration was 4.5 ± 1.4 years. After propensity score matching analysis, group B [median duration: 8.0 (6.0–16.2) years] exhibited significantly longer median operative times (85 vs. 55 min; P = 0.026), higher callus formation rates (68.8% vs. 46.9%; P = 0.029), and greater median intraoperative blood loss (35 vs. 10 mL; P = 0.017) than group A [median duration: 4.2 (3.0–5.9) years]. However, following bar removal, the groups showed no statistical differences in the surgical complication rates (group A: 6.3% vs. group B: 9.4%; P = 0.648) or median ratio of radiological improvement (an improvement on the Haller index on chest radiography; 21.0% vs. 22.2%; P = 0.308). Conclusions Delaying pectus bar removal after Nuss repair presents certain challenges but does not compromise overall outcomes. These findings suggest that a longer correction period may be unnecessary. However, further multicenter studies with long-term follow-up are warranted to assess long-term outcomes.

Abstract Background Pectus excavatum (PE) is the most common congenital abnormality of the chest wall. Most patients with PE have slim bodies. Some studies have been conducted on the physical growth of children and adolescents who underwent the Nuss procedure. This study aimed to evaluate body measurement changes in adult patients with PE after the Nuss procedure. Methods A total of 272 adult PE patients, who underwent the Nuss procedure and pectus bars removal from August 2014 to December 2020, were evaluated retrospectively. Body measurement [body height (BH), body weight (BW), and body mass index (BMI)] of the patients were collected before Nuss repair and after bar removal. We used the interquartile range (IQR) to identify and exclude outliers. Associations between changes in body measurement and clinical and radiological features were evaluated. Results The BH, BW and BMI showed significantly increased after pectus bar removal, compared to pre-Nuss procedure parameters (BH 173.8 ± 5.9 cm vs. 173.9 ± 5.9 cm, P

A quarter of Asian elephants are captive, with greater than 90% of these tamed and cared for by handlers (mahouts) in Asia. Although taming is a much-discussed welfare issue, no studies to our knowledge have empirically assessed its impact on calves, and dialogue surrounding taming often lacks perspectives of those involved. Here, we interviewed mahouts involved in taming and monitored five physiological measures (faecal glucocorticoid metabolites (FGMs), serum cortisol, glucose, creatine kinase (CK) and heterophil:lymphocyte (H:L)) over the first 10 days of taming and following six months in 41 calves undergoing taming and 16 control individuals. These measures assess the duration and intensity of stress during taming. Interviews suggested mahouts had major concerns for their safety when discussing changing taming practices, an important consideration for future management. Calf physiological measures were elevated by 50–70% (FGMs/cortisol/glucose), 135% (H:L) and greater than 500% (CK) over the first few days of taming, indicative of elevated stress, not seen to the same extent in control adults. Some measures stabilized sooner (glucose/cortisol/CK/FGM: 7–10 days) than others (H:L: one–two months), indicating mostly acute stress. Our findings inform the welfare of approximately 15 000 captive elephants around the world. Future studies should compare taming in different populations and consider calf and mahout welfare.

BackgroundIn the Greater Mekong Subregion of Southeast Asia, Plasmodium vivax malaria is endemic and causes significant morbidity. In this study, the efficacy of chloroquine for treating uncomplicated P. vivax malaria at the eastern and western borders of Myanmar was investigated.MethodsA total of 197 participants with microscopically confirmed P. vivax infection were enrolled from three townships of the southeastern (Thanbyuzayat and Kawthoung) and western (Kyauktaw) borders of Myanmar. Patients were treated with chloroquine according to the national malaria treatment guidelines and followed for 28 days.ResultsAmong the 197 enrollments, 172 completed the 28-day follow-up. Twelve recurrent P. vivax infections, all occurring in the third and fourth week, were detected, resulting in an overall cumulative rate of recurrence of 4.7% [95% confidence interval (CI) 1.5-7.8]. The incidence rate of recurrence varied among the three sites. In Thanbyuzayat township, no patients had recurrent parasitemia between days 7 and 28. In contrast, Kyauktaw township had a day 28 cumulative incidence rate of recurrence of 7.2% (95% CI 0.6-13.9%) compared to 6.9% (95% CI 0.6-13.2) in Kawthoung township.ConclusionWhile this study confirmed the relatively high clinical efficacy of chloroquine for treating P. vivax in Myanmar with modest rates of recurrent infections within 28 days of the treatment, it also revealed considerable geographical heterogeneity of chloroquine efficacy, which warrants continuous surveillance efforts.

Abstract Splice modulating antisense oligomers (AOs) are increasingly used to modulate RNA processing. While most are investigated for their use as therapeutics, AOs can also be used for basic research. This study examined their use to investigate internally and terminally truncated proprotein convertase subtilisin/kexin type 9 (PCSK9) protein isoforms. Previous studies have used plasmid or viral-vector-mediated protein overexpression to study different PCSK9 protein isoforms, creating an artificial environment within the cell. Here we designed and tested AOs to remove specific exons that encode for PCSK9 protein domains and produced protein isoforms at more physiologically relevant levels. We evaluated the isoforms’ expression, secretion, and subsequent impact on the low-density lipoprotein (LDL) receptor and its activity in Huh-7 cells. We found that modifying the Cis-His-rich domain by targeting exons 10 or 11 negatively affected LDL receptor activity and hence did not enhance LDL uptake although the levels of LDL receptor were increased. On the other hand, removing the hinge region encoded by exon 8, or a portion of the prodomain encoded by exon 2, have the potential as therapeutics for hypercholesterolemia. Our findings expand the understanding of PCSK9 isoforms and their impact on the LDL receptor and its activity at physiologically relevant concentrations.

Filanesib is a first-in-class kinesin spindle protein inhibitor which demonstrated safety and encouraging activity in combination with bortezomib and dexamethasone in relapsed/refractory multiple myeloma in a preliminary analysis of dose-escalation phase results. This multicenter study included first a dose-escalation phase to determine maximum tolerated dose of two schedules of filanesib, bortezomib, and dexamethasone and a subsequent dose-expansion phase using the maximum tolerated doses. In the dose-expansion phase, 28 patients were evaluable for safety and efficacy. The most common grade ≥3 adverse events were neutropenia (21%) and anemia (18%), which were noncumulative and reversible, and hypertension (18%). The overall response rate was 43% with median duration of response not yet reached (range, 2.8-23.7+ months) with median follow-up of 6.3 months. A post hoc analysis incorporated 29 dose-escalation phase patients who received therapeutic filanesib doses, with an overall response rate of 39% and median duration of response of 18.0 months among the 57 total patients with median progression-free survival of 8.5 months. Notably, the PFS of high risk patients was comparable at 8.5 months, driven by the patients with 1q21 gain, characterized by increased MCL-1 expression, with a PFS of 9.1 months versus 3.5 months for the remainder of high risk patients. Patients with t(11;14) also had an encouraging PFS of 15.0 months. The combination of filanesib, bortezomib, and dexamethasone continues to show safety and encouraging activity in relapsed/refractory multiple myeloma, particularly in those patients with 1q21 gain and t(11;14).