Background: Malondialdehyde (MDA) is a candidate general marker of oxidative stress (OS). We sought to assess the relation of MDA to Gulf War illness (GWI) and to a variety of exposures.

Methods: This is an observational study involving subjects from Southern California recruited from October 2011 to May 2014. MDA was assessed in 81 participants (41 GWI-cases, 40 controls). General and Gulf-specific exposures were elicited. MDA case–control comparison was restricted to 40 matched pairs. The potential association between MDA and exposures was assessed using regression analyses. Gulf-specific exposures were incorporated into a case-specific model.

Results: Plasma MDA was significantly lower in GWI-cases than controls. Composite pesticide and fuel-solvent exposures negatively predicted MDA in the total sample, as well as in the analyses that included either GWI-cases or controls only. Self-reported exposure to organophosphate (OP) nerve gas was a strong predictor for lower MDA level in veterans with GWI.

Conclusions: Past pesticide exposures predicted lower MDA in both veterans with GWI and in healthy controls.

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is a newly identified member of the coronavirus family that has caused the coronavirus disease 2019 (COVID-19) pandemic. This rapidly evolving and unrelenting SARS-CoV-2 has disrupted the lives and livelihoods of millions worldwide. As of 23 August 2021, a total of 211,373,303 COVID-19 cases have been confirmed globally with a death toll of 4,424,341. A strong understanding of the infection pathway of SARS-CoV-2, and how our immune system responds to the virus is highly pertinent for guiding the development and improvement of effective treatments. In this review, we discuss the current understanding of neutralising antibodies (NAbs) and their implications in clinical practice. The aspects include the pathophysiology of the immune response, particularly humoral adaptive immunity and the roles of NAbs from B cells in infection clearance. We summarise the onset and persistence of IgA, IgM and IgG antibodies, and we explore their roles in neutralising SARS-CoV-2, their persistence in convalescent individuals, and in reinfection. Furthermore, we also review the applications of neutralising antibodies in the clinical setting—from predictors of disease severity to serological testing to vaccinations, and finally in therapeutics such as convalescent plasma infusion.

Service members are at risk for sleep and psychological conditions affecting their readiness. Chronotype ( "morningness" or "eveningness" ) is strongly associated with sleep, health and performance. The objective of this study was to examine associations between validated measures of chronotype and sleep quality, daytime functioning, alertness, and symptoms of depression, anxiety, and post-traumatic stress disorder (PTSD) in US service members (n=298). Although predominantly young males (who skew toward eveningness in civilian populations), these Sailors skewed toward morningness (35.6% morning, 51.3% intermediate). Eveningness was associated with symptoms of depression and PTSD (P<0.01), less time in bed (P<0.05), more sleep disruption (P<0.01), and poorer daytime functioning and alertness (P<0.05). Evening types were less likely to consider sleep important for performance (P<0.05). To maximize service member readiness, schedules should be aligned with endogenous rhythms, whenever possible, and evening chronotypes may benefit from targeted interventions. Chronotype should be examined alongside health and readiness in service members.

Background: Studies have revealed the protective effect of DL-3-n-butylphthalide (NBP) against diseases associated with ischemic hypoxia. However, the role of NBP in animals with hypobaric hypoxia has not been elucidated. This study investigated the effects of NBP on rodents with acute and chronic hypobaric hypoxia.

Methods: Sprague-Dwaley rats and Kunming mice administered with NBP (0, 60, 120, and 240 mg/kg for rats and 0, 90, 180, and 360 mg/kg for mice) were placed in a hypobaric hypoxia chamber at 10,000 m and the survival percentages at 30 min were determined. Then, the time and distance to exhaustion of drug-treated rodents were evaluated during treadmill running and motor-driven wheel-track treadmill experiments, conducted at 5800 m for 3 days or 20 days, to evaluate changes in physical functions. The frequency of active escapes and duration of active escapes were also determined for rats in a shuttle-box experiment, conducted at 5800 m for 6 days or 27 days, to evaluate changes in learning and memory function. ATP levels were measured in the gastrocnemius muscle and malonaldehyde (MDA), superoxide dismutase (SOD), hydrogen peroxide (H₂O₂), glutathione peroxidase (GSH-Px), and lactate were detected in sera of rats, and routine blood tests were also performed.

Results: Survival analysis at 10,000 m indicated NBP could improve hypoxia tolerance ability. The time and distance to exhaustion for mice (NBP, 90 mg/kg) and time to exhaustion for rats (NBP, 120 and 240 mg/kg) significantly increased under conditions of acute hypoxia compared with control group. NBP treatment also significantly increased the time to exhaustion for rats when exposed to chronic hypoxia. Moreover, 240 mg/kg NBP significantly increased the frequency of active escapes under conditions of acute hypoxia. Furthermore, the levels of MDA and H₂O₂ decreased but those of SOD and GSH-Px in the sera of rats increased under conditions of acute and chronic hypoxia. Additionally, ATP levels in the gastrocnemius muscle significantly increased, while lactate levels in sera significantly decreased.

Conclusion: NBP improved physical and learning and memory functions in rodents exposed to acute or chronic hypobaric hypoxia by increasing their anti-oxidative capacity and energy supply.

With the rapid development of terahertz technologies, basic research and applications of terahertz waves in biomedicine have attracted increasing attention. The rotation and vibrational energy levels of biomacromolecules fall in the energy range of terahertz waves; thus, terahertz waves might interact with biomacromolecules. Therefore, terahertz waves have been widely applied to explore features of the terahertz spectrum of biomacromolecules. However, the effects of terahertz waves on biomacromolecules are largely unexplored. Although some progress has been reported, there are still numerous technical barriers to clarifying the relation between terahertz waves and biomacromolecules and to realizing the accurate regulation of biological macromolecules by terahertz waves. Therefore, further investigations should be conducted in the future. In this paper, we reviewed terahertz waves and their biomedical research advantages, applications of terahertz waves on biomacromolecules and the effects of terahertz waves on biomacromolecules. These findings will provide novel ideas and methods for the research and application of terahertz waves in the biomedical field.

Background: Meta-analysis is a statistical method to synthesize evidence from a number of independent studies, including those from clinical studies with binary outcomes. In practice, when there are zero events in one or both groups, it may cause statistical problems in the subsequent analysis.

Methods: In this paper, by considering the relative risk as the effect size, we conduct a comparative study that consists of four continuity correction methods and another state-of-the-art method without the continuity correction, namely the generalized linear mixed models (GLMMs). To further advance the literature, we also introduce a new method of the continuity correction for estimating the relative risk.

Results: From the simulation studies, the new method performs well in terms of mean squared error when there are few studies. In contrast, the generalized linear mixed model performs the best when the number of studies is large. In addition, by reanalyzing recent coronavirus disease 2019 (COVID-19) data, it is evident that the double-zero-event studies impact the estimate of the mean effect size.

Conclusions: We recommend the new method to handle the zero-event studies when there are few studies in a meta-analysis, or instead use the GLMM when the number of studies is large. The double-zero-event studies may be informative, and so we suggest not excluding them.

Background: Mitochondria have been shown to play vital roles during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and coronavirus disease 2019 (COVID-19) development. Currently, it is unclear whether mitochondrial DNA (mtDNA) variants, which define mtDNA haplogroups and determine oxidative phosphorylation performance and reactive oxygen species production, are associated with COVID-19 risk.

Methods: A population-based case-control study was conducted to compare the distribution of mtDNA variations defining mtDNA haplogroups between healthy controls (n=615) and COVID-19 patients (n=536). COVID-19 patients were diagnosed based on molecular diagnostics of the viral genome by qPCR and chest X-ray or computed tomography scanning. The exclusion criteria for the healthy controls were any history of disease in the month preceding the study assessment. MtDNA variants defining mtDNA haplogroups were identified by PCR-RFLPs and HVS-I sequencing and determined based on mtDNA phylogenetic analysis using Mitomap Phylogeny. Student’s t-test was used for continuous variables, and Pearson’s chi-squared test or Fisher’s exact test was used for categorical variables. To assess the independent effect of each mtDNA variant defining mtDNA haplogroups, multivariate logistic regression analyses were performed to calculate the odds ratios (OR) and 95% confidence intervals (CI) with adjustments for possible confounding factors of age, sex, smoking and diseases (including cardiopulmonary diseases, diabetes, obesity and hypertension) as determined through clinical and radiographic examinations.

Results: Multivariate logistic regression analyses revealed that the most common investigated mtDNA variations (>10% in the control population) at C5178a (in NADH dehydrogenase subunit 2 gene, ND2) and A249d (in the displacement loop region, D-loop)/T6392C (in cytochrome c oxidase I gene, CO1)/G10310A (in ND3) were associated with a reduced risk of severe COVID-19 (OR=0.590, 95%CI 0.428–0.814, P=0.001; and OR=0.654, 95%CI 0.457–0.936, P=0.020, respectively), while A4833G (ND2), A4715G (ND2), T3394C (ND1) and G5417A (ND2)/C16257a (D-loop)/C16261T (D-loop) were related to an increased risk of severe COVID-19 (OR=2.336, 95%CI 1.179–4.608, P=0.015; OR=2.033, 95%CI 1.242–3.322, P=0.005; OR=3.040, 95%CI 1.522–6.061, P=0.002; and OR=2.890, 95%CI 1.199–6.993, P=0.018, respectively).

Conclusions: This is the first study to explore the association of mtDNA variants with individual’s risk of developing severe COVID-19. Based on the case–control study, we concluded that the common mtDNA variants at C5178a and A249d/T6392C/G10310A might contribute to an individual’s resistance to developing severe COVID-19, whereas A4833G, A4715G, T3394C and G5417A/C16257a/C16261T might increase an individual’s risk of developing severe COVID-19.

Background: Aeromedical evacuation of patients with burn trauma is an important transport method in times of peace and war, during which patients are exposed to prolonged periods of hypobaric hypoxia; however, the effects of such exposure on burn injuries, particularly on burn-induced lung injuries, are largely unexplored. This study aimed to determine the effects of hypobaric hypoxia on burn-induced lung injuries and to investigate the underlying mechanism using a rat burn model.

Methods: A total of 40 male Wistar rats were randomly divided into four groups (10 in each group): sham burn (SB) group, burn in normoxia condition (BN) group, burn in hypoxia condition (BH) group, and burn in hypoxia condition with treatment intervention (BHD) group. Rats with 30% total body surface area burns were exposed to hypobaric hypoxia (2000 m altitude simulation) or normoxia conditions for 4 h. Deoxyribonuclease I (DNase I) was administered systemically as a treatment intervention. Systemic inflammatory mediator and mitochondrial deoxyribonucleic acid (mtDNA) levels were determined. A histopathological evaluation was performed and the acute lung injury (ALI) score was determined. Malonaldehyde (MDA) content, myeloperoxidase (MPO) activity, and the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome level were determined in lung tissues. Data among groups were compared using analysis of variance followed by Tukey’s test post hoc analysis.

Results: Burns resulted in a remarkably higher level of systemic inflammatory cytokines and mtDNA release, which was further heightened by hypobaric hypoxia exposure (P<0.01). Moreover, hypobaric hypoxia exposure gave rise to increased NLRP3 inflammasome expression, MDA content, and MPO activity in the lung (P<0.05 or P<0.01). Burn-induced lung injuries were exacerbated, as shown by the histopathological evaluation and ALI score (P<0.01). Administration of DNase I markedly reduced mtDNA release and systemic inflammatory cytokine production. Furthermore, the NLRP3 inflammasome level in lung tissues was decreased and burn-induced lung injury was ameliorated (P<0.01).

Conclusions: Our results suggested that simulated aeromedical evacuation further increased burn-induced mtDNA release and exacerbated burn-induced inflammation and lung injury. DNase I reduced the release of mtDNA, limited mtDNA-induced systemic inflammation, and ameliorated burn-induced ALI. The intervening mtDNA level is thus a potential target to protect from burn-induced lung injury during aeromedical conditions and provides safer air evacuations for severely burned patients.

Background: Tension pneumothorax is one of the leading causes of preventable death on the battlefield. Current prehospital diagnosis relies on a subjective clinical impression complemented by a manual thoracic and respiratory examination. These techniques are not fully applicable in field conditions and on the battlefield, where situational and environmental factors may impair clinical capabilities. We aimed to assemble a device able to sample, analyze, and classify the unique acoustic signatures of pneumothorax and hemothorax.

Methods: Acoustic data was obtained with simultaneous use of two sensitive digital stethoscopes from the chest wall of an ex-vivo porcine model. Twelve second samples of acoustic data were obtained from the in-house assembled digital stethoscope system during mechanical ventilation. The thoracic cavity was injected with increasing volumes of 200, 400, 600, 800, and 1000 ml of air or saline to simulate pneumothorax and hemothorax, respectively. The data was analyzed using a multi-objective genetic algorithm that was used to develop an optimal mathematical detector through the process of artificial evolution, a cutting-edge approach in the artificial intelligence discipline.

Results: The in-house assembled dual digital stethoscope system and developed genetic algorithm achieved an accuracy, sensitivity and specificity ranging from 64% to 100%, 63% to 100%, and 63% to 100%, respectively, in classifying acoustic signal as associated with pneumothorax or hemothorax at fluid injection levels of 400 ml or more, and regardless of background noise.

Conclusions: We present a novel, objective device for rapid diagnosis of potentially lethal thoracic injuries. With further optimization, such a device could provide real-time detection and monitoring of pneumothorax and hemothorax in battlefield conditions.

In response to an outbreak of coronavirus disease 2019 (COVID-19) within a cluster of Navy personnel in Sri Lanka commencing from 22nd April 2020, an aggressive outbreak management program was launched by the Epidemiology Unit of the Ministry of Health. To predict the possible number of cases within the susceptible population under four social distancing scenarios, the COVID-19 Hospital Impact Model for Epidemics (CHIME) was used. With increasing social distancing, the epidemiological curve flattened, and its peak shifted to the right. The observed or actually reported number of cases was above the projected number of cases at the onset; however, subsequently, it fell below all predicted trends. Predictive modelling is a useful tool for the control of outbreaks such as COVID-19 in a closed community.