Armed Forces Research Institute of Medical Science

OBJECTIVES: To characterize telomere length (TL) and determine biological and clinical factors associated with telomere shortening among individuals leukocyte telomere length (LTL) receiving an advanced wellness program at a clinical wellness institution in Thailand. MATERIALS AND METHODS: This retrospective study included adults aged ≥18 years who underwent TL assessment as part of advanced wellness programs at two clinical wellness institutions in Thailand. Demographic, hormonal, micronutrient, metabolic, and clinical laboratory data were extracted from electronic medical records and laboratory databases within two weeks before or after TL measurement. Associations between TL and related demographic, hormonal, micronutrient, metabolic, and clinical variables were assessed using Pearson’s correlation coefficient. A two-sided p-value < 0.05 was considered statistically significant. RESULTS: Among 1,684 records, TL –derived biological aging was significantly associated with multiple biological domains. Higher levels of insulin-like growth factor 1 (IGF-1) and dehydroepiandrosterone sulfate (DHEA-S) were positively correlated with slower aging, while cortisol showed no significant association. Markers of glucose metabolism, including fasting glucose, HbA1c, and insulin, demonstrated consistent inverse correlations with TL, indicating accelerated aging with poorer glycemic control. Lipid parameters showed modest associations: total cholesterol and low-density lipoprotein cholesterol (LDL-C) were positively associated with slower aging, whereas triglycerides were inversely associated with faster aging. Ferritin levels were negatively correlated with telomere-related aging, while C-reactive protein (CRP) showed no consistent relationship. Several micronutrients and antioxidants, particularly magnesium, selenium, folate, vitamin D, and coenzyme Q10, exhibited significant inverse associations with accelerated aging, most prominently in the fast-aging group. CONCLUSION: Telomere shortening was associated with specific biological domains, particularly metabolic regulation and endocrine function, followed by micronutrient status, whereas associations with acute inflammatory markers were limited. These findings support the role of TL as a contextual biomarker for investigating biological aging within clinical wellness institutions in Thailand settings.

CR6-interacting factor 1 (CRIF1) is essential for the synthesis and insertion of mitochondrial oxidative phosphorylation (OXPHOS) complexes. Although Crif1 deficiency has been linked to mitochondrial dysfunction in various tissues, its role in cardiac function remains unclear. Therefore, this study aimed to investigate the role of Crif1 in regulating mitochondrial function in the heart. To determine the role of Crif1 and examine mitochondrial dysfunction in the heart, we generated cardiac-specific Crif1 knock-down mice using a Myh6-Cre system. Mitochondrial function was assessed by measuring oxygen consumption rates. Histological and echocardiographic examinations were performed at baseline and 2 weeks after isoproterenol infusion. Crif1 knock-down in the heart led to structural mitochondrial abnormalities and decreased maximal oxygen consumption rates in cardiomyocytes. Although cardiac-specific Crif1 knock-down resulted in mitochondrial dysfunction, the cardiac phenotype remained normal showing preserved ejection fraction (EF) and fractional shortening (FS). However, cardiac dysfunction was aggravated under isoproterenol-induced stress, resulting in a decreased EF and FS. Cardiac hypertrophy, a typical adaptive response to isoproterenol stimulation, was attenuated. These findings suggest that Crif1 is critical for maintaining the structure and function of mitochondria in cardiomyocytes. Additionally, mitochondrial abnormalities in the heart impair stress adaptation, leading to aggravated cardiac dysfunction under stress.

Cerebral malaria (CM) is a severe complication caused by Plasmodium falciparum infection, leading to persistent neurological impairments in survivors. To understand the complex mechanisms and investigate advanced diagnostic and treatment strategies targeting human CM, we utilize Plasmodium coatneyi-infected male rhesus macaques, a non-human primate model closely resembling P. falciparum infection in humans. Through differential gene expression analysis, our study demonstrates methylene blue’s efficacy in reversing the detrimental effects of infection on the brainstem. Furthermore, by comparing our brainstem dataset from P. coatneyi-infected Macaca mulatta with two additional transcriptomic datasets (P. coatneyi-infected M. mulatta blood and P. falciparum-infected human blood), we identify nine genes associated with CM severity. Most of these genes are expressed in neutrophils, indicating their potential as blood biomarkers for diagnosing P. falciparum-induced fatal CM. This research highlights the necessity for new CM treatments and reveals promising biomarkers that could improve diagnosis and prognosis in affected individuals.

This study represents the first investigation into the prevalence of pathogenic bacteria in isolated, free-ranging Eastern Grey Kangaroos (Macropus giganteus) inhabiting a human-shared environment. Samples were collected from the nasal and rectal passages of state-authorised culls of M. giganteus within a military training area, where recruits had reported recurrent cases of skin and soft tissue infections. The objective was to identify clinically relevant pathogenic microorganisms present in the nasal and rectal flora of these kangaroos. Analysis revealed carriage rates of 11% for methicillin-sensitive Staphylococcus aureus (MSSA) and 2% for methicillin-resistant S. aureus (MRSA). Other potentially pathogenic bacteria isolated included Pseudomonas spp., Streptococcus (Groups B and D), Acinetobacter spp., and multiple coagulase-negative Staphylococcus (CoNS) species. Notably, CoNS species were present in 17% of nasal isolates, with Mammaliicoccus sciuri (formerly Staphylococcus sciuri) detected in 41% of these isolates, suggesting a potential reservoir for antibiotic resistance genes and virulence factors. These findings support a One Health perspective, highlighting the interconnectedness of pathogenic bacteria, M. giganteus, humans, and their shared environment.

Understanding the selective forces acting upon HIV early in infection is crucial to design prevention strategies. By leveraging deep sequencing and the short diagnostic intervals of the FRESH and RV217 cohorts (median 4 days) between the last-negative and first-positive RNA tests, we captured a precise and early snapshot of acute HIV infection. The frequency of multiple transmitted viruses of 38% in these as well as placebo recipients from the AMP trials was higher than previously published, with the true frequency likely to be higher. The relative abundance of lineages fluctuated substantially over time in two-thirds of the multilineage infections, generating uncertainty in identifying the specific viruses that were transmitted and founding the infection. Viral populations exhibited diversity and selection on the Gag and Env proteins at the earliest times examined, with sites inferred to be undergoing negative selection most evident. These data may help explain vaccination failures and provide new targets for prevention.

We describe the genomes of three lytic Pseudomonas aeruginosa phages of the genus Phikmvvirus. The genomes of phages vB_Pae4841-AFR43, vB_Pae10145-KEN1, and vB_Pae9718-KEN10 consist of 43,426, 43,406, and 43,118 bp, with 62.4%, 62.3%, and 62.2% GC content, contain 63, 66, and 64 coding sequences, respectively, and no tRNA genes.

Abstract Background Previous studies suggested that that human adenovirus (HAdV) is the most prevalent in patients with acute lower respiratory tract infection and is the most common cause of pneumonia in Korean military. A sentinel surveillance program was initiated to investigate the incidence of acute respiratory illness (ARI) and characteristics of type-specific HAdV respiratory infections in Korean military trainees. Weakly incidence of acute respiratory infection per 1,000 persons in military trainees Methods To calculate the incidence of ARI, all new trainees with febrile respiratory illness (FRI) who were required to visit the infirmaries at three military training centers were enrolled from September 2016 to August 2017. Of soldiers with FRI, 10 nasopharyngeal or throat swab specimens were weakly collected for for HAdV molecular typing. Weakly proportion of adenovirus infection in trainees with acute respiratory infection Results The incidence of ARI, which was defined as the number of weakly ARI cases per 1,000 trainees, was estimated at 7.5-375.5 cases per 1,000 trainees with peaks between 41th week and 10th week in 2016-17 season. Of 1,079 patients with FRI, HAdVs were detected in 518 (48.0%) patients. HAdV type 55 was the most prevalent virus (98.6%, 511 cases). HAdV type 2 was only identified in 7 cases. Although HAdV associated ARI occurred throughout the year, Patients with HAdV infection were primarily observed during winter and spring. The clinical diagnoses in patients with HAdV associated ARI were almost pharyngotonsillitis (96.3%). Pneumonia (2.2%) was uncommon manifestation. There was no statistically significant difference in demographic characteristics and presenting symptoms and signs between HAdV-positive and HAdV-negative patients. Conclusion HAdV-55 was the most prevalent type in Korean soldiers with HAdV-associated ARI. Adenovirus type 55 was revealed to be the most important causative agent of acute respiratory infection in military trainees. Further studies are required to verify which HAdV types are associated with ARI in military recruits. Disclosures All Authors: No reported disclosures

ABSTRACTAedes aegpyti mosquitoes are vectors of several viruses of major public health importance, and many new control strategies target mating behaviour. Mating in this species occurs in swarms characterised by male scramble competition and female choice. These mating swarms have a male‐biased operational sex ratio, which is expected to generate intense competition among males for mating opportunities. However, it is not known what proportion of swarming males successfully mate with females, how many females each male is able to mate with, and to what extent any variation in the male mating success phenotype can be explained by genetic variation. Here, we describe a novel assay to quantify individual male mating success in the presence of operational sex ratios characteristic of Ae. aegypti. Our results demonstrate that male mating success is skewed. Most males do not mate despite multiple opportunities, and very few males mate with multiple females. We compared measures of male mating success between fathers and sons and between full siblings to estimate the heritability of the trait in the narrow h2 and broad H2 sense, respectively. We found significant broad sense heritability estimates but little evidence for additive genetic effects, suggesting a role for dominance or epistatic effects and/or larval rearing environment in male mating success. These findings enhance our understanding of sexual selection in this species and have important implications for mass‐release programmes that rely on the release of competitive males.

Infections caused by antimicrobial-resistant Acinetobacter baumannii pose a significant threat to human health, particularly in the context of hospital-acquired infections. As existing antibiotics lose efficacy against Acinetobacter isolates, there is an urgent need for the development of novel antimicrobial agents. In this study, we assessed 400 structurally diverse compounds from the Medicines for Malaria Pandemic Response Box for their activity against two clinical isolates of A. baumannii: A. baumannii 5075, known for its extensive drug resistance, and A. baumannii QS17-1084, obtained from an infected wound in a Thai patient. Among the compounds tested, seven from the Pathogen box exhibited inhibitory effects on the in vitro growth of A. baumannii isolates, with IC50s ≤ 48 µM for A. baumannii QS17-1084 and IC50s ≤ 17 µM for A. baumannii 5075. Notably, two of these compounds, MUT056399 and MMV1580854, shared chemical scaffolds resembling triclosan. Further investigations involving drug combinations identified five synergistic drug combinations, suggesting potential avenues for therapeutic development. The combination of MUT056399 and brilacidin against A. baumannii QS17-1084 and that of MUT056399 and eravacycline against A. baumannii 5075 showed bactericidal activity. These combinations significantly inhibited biofilm formation produced by both A. baumannii strains. Our findings highlight the drug combinations as promising candidates for further evaluation in murine wound infection models against multidrug-resistant A. baumannii. These compounds hold potential for addressing the critical need for effective antibiotics in the face of rising antimicrobial resistance.