Hypobaric hypoxia modulated structural characteristics of circulating cell-free DNA in high-altitude pulmonary edema.

The utility of cell-free (cf) DNA has extended as a surrogate or clinical biomarker for various diseases. However, a more profound and expanded understanding of the diverse cfDNA population and its correlation with physiological phenotypes and environmental factors is imperative for using its full potential. The high-altitude (HA; altitude > 2,500 m above sea level) environment characterized by hypobaric hypoxia offers an observational case-control design to study the differential cfDNA profile in patients with high-altitude pulmonary edema (HAPE) (number of subjects, n = 112) and healthy HA sojourners (n = 111). The present study investigated cfDNA characteristics such as concentration, fragment length size, degree of integrity, and subfractions reflecting mitochondrial-cfDNA copies in the two groups. The total cfDNA level was significantly higher in patients with HAPE, and the level increased with increasing HAPE severity (P = 0.0036). A lower degree of cfDNA integrity of 0.346 in patients with HAPE (P = 0.001) indicated the prevalence of shorter cfDNA fragments in circulation in patients compared with the healthy HA sojourners. A significant correlation of cfDNA characteristics with the peripheral oxygen saturation levels in the patient group demonstrated the translational relevance of cfDNA molecules. The correlation was further supported by multivariate logistic regression and receiver operating characteristic curve. To our knowledge, our study is the first to highlight the association of higher cfDNA concentration, a lower degree of cfDNA integrity, and increased mitochondrial-derived cfDNA population with HAPE disease severity. Further deep profiling of cfDNA fragments, which preserves cell-type specific genetic and epigenetic features, can provide dynamic physiological responses to hypoxia.NEW & NOTEWORTHY This study observed altered cell-free (cf) DNA fragment patterns in patients with high-altitude pulmonary edema and the significant correlation of these patterns with peripheral oxygen saturation levels. This suggests deep profiling of cfDNA fragments in the future may identify genetic and epigenetic mechanisms underlying physiological and pathophysiological responses to hypoxia.

Respiratory tract infection: an unfamiliar risk factor in high-altitude pulmonary edema.

The dramatic changes in physiology at high altitude (HA) as a result of the characteristic hypobaric hypoxia condition can modify innate and adaptive defense mechanisms of the body. As a consequence, few sojourners visiting HA with mild or asymptomatic infection may have an enhanced susceptibility to high-altitude pulmonary edema (HAPE), an acute but severe altitude sickness. It develops upon rapid ascent to altitudes above 2500 m, in otherwise healthy individuals. Though HAPE has been studied extensively, an elaborate exploration of the HA disease burden and the potential risk factors associated with its manifestation are poorly described. The present review discusses respiratory tract infection (RTI) as an unfamiliar but important risk factor in enhancing HAPE susceptibility in sojourners for two primary reasons. First, the symptoms of RTI s resemble those of HAPE. Secondly, the imbalanced pathways contributing to vascular dysfunction in HAPE also participate in the pathogenesis of the infectious processes. These pathways have a crucial role in shaping host response against viral and bacterial infections and may further worsen the clinical outcomes at HA. Respiratory tract pathogenic agents, if screened in HAPE patients, can help in ascertaining their role in disease risk and also point toward their association with the disease severity. The microbial screenings and identifications of pathogens with diseases are the foundation for describing potential molecular mechanisms underlying host response to the microbial challenge. The prior knowledge of such infections may predict the manifestation of disease etiology and provide better therapeutic options.

Epidemiology of hepatitis B and C viral infections in Ladakh region.

BACKGROUND: Little is known about the prevalence of hepatitis B virus (HBV) and hepatitis C virus (HCV) infections in Ladakh, a mountainous region with low population density. We, therefore, determined these and tried to identify risk factors associated with these infections. METHODS: Randomly selected residents of Ladakh region were tested for hepatitis B surface antigen (HBsAg), antibodies to hepatitis B core antigen (anti-HBc) and antibodies to HCV (anti-HCV). A subset of HBsAg-positive persons were tested for hepatitis B e-antigen (HBeAg) and HBV DNA and those with anti-HCV for HCV RNA. Viral genotype was also determined. RESULTS: Of the 2674 subjects, 141 (5.3%) tested positive for HBsAg, i.e. had current HBV infection and 339 (12.7%) tested positive for either HBsAg and or anti-HBc, i.e. had either current or past infection with HBV. Anti-HCV antibody was detected in 22 (0.8%) subjects. The HBsAg positivity rate was higher in Kargil district (8.3%) than in Leh district (3.3%). No particular risk factor was identified for either infection. Of the 141 and 22 specimens that contained HBsAg and anti-HCV, respectively (one had both), 74 and none tested positive for HBV DNA and HCV RNA, respectively. Of the 29 specimens that had sufficient HBV DNA for genotyping, 21, 7, and 1 specimens had HBV genotypes D, C, and A, respectively. CONCLUSION: The overall prevalence of HBV infection seems to be higher in Ladakh region, especially the Kargil district. The prevalence of anti-HCV was similar to that in other parts of India. ᅟ ᅟ.

Neurobrucellosis Presenting as Acute Psychosis.

A 45-year-old female without any past or family history of psychiatric illness presented to the emergency department with complaints of abnormal behavior, irrelevant talking, restlessness, episodic crying, and decreased sleep of 2-day duration. On detailed interview, the attendants gave a history of an intermittent headache of 6-month duration and hearing impairment of 4-month duration. On investigation, her cerebrospinal fluid was reactive, and brucella titers were positive. She received appropriate treatment for 6 months and a short course of antipsychotics. Her symptoms settled, but she had persistent hearing loss. Psychosis as well as hearing loss is a very rare presentation of brucellosis. The case highlights the importance of considering neurobrucellosis as a differential diagnosis in patients with any unexplained neuropsychiatric symptoms such as acute psychosis or hearing loss.