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.

Association of transient mitochondrial functional impairment with acute heat exposure in children from Muzaffarpur region of Bihar, India.

Over the past several years, the Muzaffarpur district of Bihar (India) has witnessed recurrent outbreaks of acute encephalitis illness of unknown etiology, called acute encephalitis syndrome (AES) among young children, especially during the peak-summer season. Pesticide exposure, viral encephalitis, and litchi toxin intake have all been postulated as potential sources of the ailment. However, no conclusive etiology for AES has been identified in the affected children. During recent rounds of the outbreak, metabolic abnormalities have been documented in these children, and a direct correlation was observed between higher environmental temperature during the peak-summer month and AES caseload. The clinical and metabolic profiles of these children suggested the possible involvement of mitochondrial dysfunction during heat stress as one of the several contributory factors leading to multisystem metabolic derangement. The present study observed that mitochondrial function parameters such as cell death, mitochondrial membrane potential, oxidative stress, and mitochondrial pathway-related gene expression in peripheral blood mononuclear cells (PBMCs) isolated from children were affected in peak-summer when compared to post-summer months. Similar observations of mitochondrial function parameters along with impaired bioenergetic parameters were demonstrated in the heat-exposed model of PBMCs isolated from healthy adult individuals. In conclusion, the results suggested that there is an association of transient mitochondrial dysfunction when exposed to sustained heat during the summer months. One may consider mitochondrial dysfunction as one of the important factors leading to an outbreak of AES among the children from affected regions though this needs to be substantiated with further studies.

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.

Expansion of Shishper Glacier lake and recent glacier lake outburst flood (GLOF), Gilgit-Baltistan, Pakistan.

Shishper lake is an ice-dammed lake in northern Pakistan that has drained twice within one (1) year. The parameters evaluated in this paper are the lake's area, volume, peak discharge, and its outburst events using various satellite images from November 2018 to June 2020. Based on satellite imagery and empirical approaches, the lake formed in November 2018 and reached a maximum of 0.34 km2 till its first breach that occurred on 22 June 2019. Since June 2019, the lake drained till September 2019. After that, the flow was blocked again, and the lake expanded to an area of 0.27 km2 till its second outburst event that happened on May 29, 2020. Eight cross-sectional profiles of Hassanabad ravine are generated based on peak discharge in the lake's rapid outburst. The results indicate that, the peak discharge for both 2019 and 2020 was more than 4500 m3 s-1. Delineation of downstream Hassanabad ravine shows that more than 1000 buildings and 2000+ population is prone to flood. However, the lake drain twice steadily, but it has a high potential to cause severe damages if it bursts abruptly.

Proteus syndrome and hypothyroidism. An unusual association.

We present a case of a 3½-year-old girl diagnosed as Proteus syndrome with severe cosmetic disfigurement-macrodactyly, hemi-hypertrophy of the face and limbs, megalencephaly, lymph edema of both hands and feet along with severe global developmental delay. She was found to have severe recalcitrant epilepsy and also primary hypothyroidism; the association of which is not mentioned in the previous literature.

Determination of the risk associated with the natural and anthropogenic radionuclides from the soil of Skardu in Central Karakoram.

The radioactivity levels were determined in 39 soil samples from six towns of Skardu using gamma-ray spectrometry. The samples were collected at an average altitude of 2293 m above sea level in Central Karakoram. The activity concentration data were analysed by principal component analysis for outlier detection and data structure elucidation and for frequency distributions. The median activity concentrations of (226)Ra, (232)Th, (40)K and (137)Cs were found to be 49.8 ± 12.6, 80.9 ± 18.7, 977 ± 91 and 4.37 ± 4.08 Bq kg(-1), respectively. An uncertainty analysis showed that the main contribution to uncertainty budget was from the counting statistics and uncertainty in the reference activity of standard. The activity concentration data showed a positive significant correlation between (226)Ra and (232)Th. Three hazard indices named the radium equivalent activity, external hazard index and internal hazard index were calculated. In the total activity concentration, (40)K accounted for the most (87.5 %), whilst in the radium equivalent activity, (232)Th contributed the most (48.5 %). In the Skardu samples, the air-absorbed dose rate was found to be 112 ± 17 nGy h(-1), annual effective dose rate from terrestrial to be 243 ± 38 µSv y(-1), effective dose rate due to the deposition of (137)Cs on soil to be 1.1 ± 2.4 µSv y(-1) and dose rate from the cosmic radiations to be 1371 ± 107 µSv y(-1). The ratio of mass fractions of Th/U was 4.8 ± 0.6.The results were compared with the similar measurements made in other parts of the world. A comparison with the other cities of Pakistan revealed that the soil in Skardu presented the highest external exposure rate.

Soil radioactivity levels and radiological risk assessment in the highlands of Hunza, Pakistan.

This paper deals with the determination of (226)Ra, (232)Th, (40)K and (137)Cs in 42 soil samples collected from eight towns of Hunza district, at an average altitude of 2267 m, using gamma-ray spectrometry. The activity concentration data were analysed for frequency distribution and other descriptive measures. Risk assessment was done by calculating the hazard indices, air absorbed dose rate and external annual effective dose rate due to cosmic radiations, terrestrial radionuclides and (137)Cs deposited on the surface of the earth. Both indoor and outdoor occupancy factors were taken into account. The average dose rate due to cosmic radiation was estimated as 828 ± 87 µSv y(-1), from external terrestrial radiation as 97 ± 20 µSv y(-1) and from (137)Cs as 1.05 µSv y(-1) for a total annual effective dose rate of 926 ± 92 µSv. The results of the present study were discussed and compared with other similar studies performed in East Asia. The present study indicates that Hunza can be ranked among those areas having a high level of dose rate not only from cosmic rays but also from terrestrial radionuclides. This paper also proposes another measure of radiation hazard called 'radium equivalent for internal exposure'.

Determination of the natural and anthropogenic radioactivity in the soil of Gilgit--a town in the foothills of Hindukush range.

The activity concentration of terrestrial (226Ra, 232Th, and 40K) and anthropogenic gamma-emitting radionuclide (137Cs) have been analyzed in 48 soil samples collected from Gilgit, a famous city for mountaineers and tourists in northern Pakistan, at an average altitude of 1,550 m, using gamma-ray spectrometry. The data analysis includes descriptive statistics, radium equivalent activity and its principal component analysis, air absorbed dose rate, annual effective dose rate, and collective effective dose equivalent. It is found that the level of cosmic exposure is high in Gilgit relative to the world average values, but the average outdoor annual effective dose rate from terrestrial radionuclides is lower as compared to its value in the soil of Punjab, Pakistan, and the world average values found in United Nations Scientific Committee on the Effects of Atomic Radiation (UNSCEAR) for the general public. The median annual effective dose rate produced by 137Cs was 0.11 microSv y-1.