Showing papers in "Military Medical Research in 2020"

The origin, transmission and clinical therapies on coronavirus disease 2019 (COVID-19) outbreak - an update on the status.

Abstract: An acute respiratory disease, caused by a novel coronavirus (SARS-CoV-2, previously known as 2019-nCoV), the coronavirus disease 2019 (COVID-19) has spread throughout China and received worldwide attention. On 30 January 2020, World Health Organization (WHO) officially declared the COVID-19 epidemic as a public health emergency of international concern. The emergence of SARS-CoV-2, since the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002 and Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, marked the third introduction of a highly pathogenic and large-scale epidemic coronavirus into the human population in the twenty-first century. As of 1 March 2020, a total of 87,137 confirmed cases globally, 79,968 confirmed in China and 7169 outside of China, with 2977 deaths (3.4%) had been reported by WHO. Meanwhile, several independent research groups have identified that SARS-CoV-2 belongs to β-coronavirus, with highly identical genome to bat coronavirus, pointing to bat as the natural host. The novel coronavirus uses the same receptor, angiotensin-converting enzyme 2 (ACE2) as that for SARS-CoV, and mainly spreads through the respiratory tract. Importantly, increasingly evidence showed sustained human-to-human transmission, along with many exported cases across the globe. The clinical symptoms of COVID-19 patients include fever, cough, fatigue and a small population of patients appeared gastrointestinal infection symptoms. The elderly and people with underlying diseases are susceptible to infection and prone to serious outcomes, which may be associated with acute respiratory distress syndrome (ARDS) and cytokine storm. Currently, there are few specific antiviral strategies, but several potent candidates of antivirals and repurposed drugs are under urgent investigation. In this review, we summarized the latest research progress of the epidemiology, pathogenesis, and clinical characteristics of COVID-19, and discussed the current treatment and scientific advancements to combat the epidemic novel coronavirus.

A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)

Abstract: In December 2019, a new type viral pneumonia cases occurred in Wuhan, Hubei Province; and then named “2019 novel coronavirus (2019-nCoV)” by the World Health Organization (WHO) on 12 January 2020. For it is a never been experienced respiratory disease before and with infection ability widely and quickly, it attracted the world’s attention but without treatment and control manual. For the request from frontline clinicians and public health professionals of 2019-nCoV infected pneumonia management, an evidence-based guideline urgently needs to be developed. Therefore, we drafted this guideline according to the rapid advice guidelines methodology and general rules of WHO guideline development; we also added the first-hand management data of Zhongnan Hospital of Wuhan University. This guideline includes the guideline methodology, epidemiological characteristics, disease screening and population prevention, diagnosis, treatment and control (including traditional Chinese Medicine), nosocomial infection prevention and control, and disease nursing of the 2019-nCoV. Moreover, we also provide a whole process of a successful treatment case of the severe 2019-nCoV infected pneumonia and experience and lessons of hospital rescue for 2019-nCoV infections. This rapid advice guideline is suitable for the first frontline doctors and nurses, managers of hospitals and healthcare sections, community residents, public health persons, relevant researchers, and all person who are interested in the 2019-nCoV.

Methodological quality (risk of bias) assessment tools for primary and secondary medical studies: what are they and which is better?

Abstract: Methodological quality (risk of bias) assessment is an important step before study initiation usage. Therefore, accurately judging study type is the first priority, and the choosing proper tool is also important. In this review, we introduced methodological quality assessment tools for randomized controlled trial (including individual and cluster), animal study, non-randomized interventional studies (including follow-up study, controlled before-and-after study, before-after/ pre-post study, uncontrolled longitudinal study, interrupted time series study), cohort study, case-control study, cross-sectional study (including analytical and descriptive), observational case series and case reports, comparative effectiveness research, diagnostic study, health economic evaluation, prediction study (including predictor finding study, prediction model impact study, prognostic prediction model study), qualitative study, outcome measurement instruments (including patient - reported outcome measure development, content validity, structural validity, internal consistency, cross-cultural validity/ measurement invariance, reliability, measurement error, criterion validity, hypotheses testing for construct validity, and responsiveness), systematic review and meta-analysis, and clinical practice guideline. The readers of our review can distinguish the types of medical studies and choose appropriate tools. In one word, comprehensively mastering relevant knowledge and implementing more practices are basic requirements for correctly assessing the methodological quality.

Perceived infection transmission routes, infection control practices, psychosocial changes, and management of COVID-19 infected healthcare workers in a tertiary acute care hospital in Wuhan: a cross-sectional survey.

Abstract: Many healthcare workers were infected by coronavirus disease 2019 (COVID-19) early in the epidemic posing a big challenge for epidemic control. Hence, this study aims to explore perceived infection routes, influencing factors, psychosocial changes, and management procedures for COVID-19 infected healthcare workers. This is a cross-sectional, single hospital-based study. We recruited all 105 confirmed COVID-19 healthcare workers in the Zhongnan Hospital of Wuhan University from February 15 to 29, 2020. All participants completed a validated questionnaire. Electronic consent was obtained from all participants. Perceived causes of infection, infection prevention, control knowledge and behaviour, psychological changes, symptoms and treatment were measured. Finally, 103 professional staff with COVID-19 finished the questionnaire and was included (response rate: 98.1%). Of them, 87 cases (84.5%) thought they were infected in working environment in hospital, one (1.0%) thought their infection was due to the laboratory environment, and 5 (4.9%) thought they were infected in daily life or community environment. Swab of throat collection and physical examination were the procedures perceived as most likely causing their infection by nurses and doctors respectively. Forty-three (41.8%) thought their infection was related to protective equipment, utilization of common equipment (masks and gloves). The top three first symptoms displayed before diagnosis were fever (41.8%), lethargy (33.0%) and muscle aches (30.1%). After diagnosis, 88.3% staff experienced psychological stress or emotional changes during their isolation period, only 11.7% had almost no emotional changes. Arbidol (Umifenovir; an anti-influza drug; 69.2%) was the drug most commonly used to target infection in mild and moderate symptoms. The main perceived mode of transmission was not maintaining protection when working at a close distance and having intimate contact with infected cases. Positive psychological intervention is necessary.

Biodegradable materials for bone defect repair

Abstract: Compared with non-degradable materials, biodegradable biomaterials play an increasingly important role in the repairing of severe bone defects, and have attracted extensive attention from researchers. In the treatment of bone defects, scaffolds made of biodegradable materials can provide a crawling bridge for new bone tissue in the gap and a platform for cells and growth factors to play a physiological role, which will eventually be degraded and absorbed in the body and be replaced by the new bone tissue. Traditional biodegradable materials include polymers, ceramics and metals, which have been used in bone defect repairing for many years. Although these materials have more or fewer shortcomings, they are still the cornerstone of our development of a new generation of degradable materials. With the rapid development of modern science and technology, in the twenty-first century, more and more kinds of new biodegradable materials emerge in endlessly, such as new intelligent micro-nano materials and cell-based products. At the same time, there are many new fabrication technologies of improving biodegradable materials, such as modular fabrication, 3D and 4D printing, interface reinforcement and nanotechnology. This review will introduce various kinds of biodegradable materials commonly used in bone defect repairing, especially the newly emerging materials and their fabrication technology in recent years, and look forward to the future research direction, hoping to provide researchers in the field with some inspiration and reference.

Chinese expert consensus on diagnosis and treatment of coagulation dysfunction in COVID-19

Abstract: Since December 2019, a novel type of coronavirus disease (COVID-19) in Wuhan led to an outbreak throughout China and the rest of the world. To date, there have been more than 1,260,000 COVID-19 patients, with a mortality rate of approximately 5.44%. Studies have shown that coagulation dysfunction is a major cause of death in patients with severe COVID-19. Therefore, the People’s Liberation Army Professional Committee of Critical Care Medicine and Chinese Society on Thrombosis and Hemostasis grouped experts from the frontline of the Wuhan epidemic to come together and develop an expert consensus on diagnosis and treatment of coagulation dysfunction associated with a severe COVID-19 infection. This consensus includes an overview of COVID-19-related coagulation dysfunction, tests for coagulation, anticoagulation therapy, replacement therapy, supportive therapy and prevention. The consensus produced 18 recommendations which are being used to guide clinical work.

Chemoprophylaxis, diagnosis, treatments, and discharge management of COVID-19: An evidence-based clinical practice guideline (updated version)

Abstract: The novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the cause of a rapidly spreading illness, coronavirus disease 2019 (COVID-19), affecting more than seventeen million people around the world. Diagnosis and treatment guidelines for clinicians caring for patients are needed. In the early stage, we have issued “A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)”; now there are many direct evidences emerged and may change some of previous recommendations and it is ripe for develop an evidence-based guideline. We formed a working group of clinical experts and methodologists. The steering group members proposed 29 questions that are relevant to the management of COVID-19 covering the following areas: chemoprophylaxis, diagnosis, treatments, and discharge management. We searched the literature for direct evidence on the management of COVID-19, and assessed its certainty generated recommendations using the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach. Recommendations were either strong or weak, or in the form of ungraded consensus-based statement. Finally, we issued 34 statements. Among them, 6 were strong recommendations for, 14 were weak recommendations for, 3 were weak recommendations against and 11 were ungraded consensus-based statement. They covered topics of chemoprophylaxis (including agents and Traditional Chinese Medicine (TCM) agents), diagnosis (including clinical manifestations, reverse transcription-polymerase chain reaction (RT-PCR), respiratory tract specimens, IgM and IgG antibody tests, chest computed tomography, chest x-ray, and CT features of asymptomatic infections), treatments (including lopinavir-ritonavir, umifenovir, favipiravir, interferon, remdesivir, combination of antiviral drugs, hydroxychloroquine/chloroquine, interleukin-6 inhibitors, interleukin-1 inhibitors, glucocorticoid, qingfei paidu decoction, lianhua qingwen granules/capsules, convalescent plasma, lung transplantation, invasive or noninvasive ventilation, and extracorporeal membrane oxygenation (ECMO)), and discharge management (including discharge criteria and management plan in patients whose RT-PCR retesting shows SARS-CoV-2 positive after discharge). We also created two figures of these recommendations for the implementation purpose. We hope these recommendations can help support healthcare workers caring for COVID-19 patients.

Expert consensus on the diagnosis and treatment of heat stroke in China.

Abstract: Heat stroke (HS) is a fatal disease caused by thermal damage in the body, and it has a very high mortality rate. In 2015, the People’s Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China, Expert consensus on standardized diagnosis and treatment for heat stroke. With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years, the 2015 consensus no longer meet the requirements for HS prevention and treatment. It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage, is more practical and is more in line with China’s national conditions. This new expert consensus includes new concept of HS, recommendations for laboratory tests and auxiliary examinations, new understanding of diagnosis and differential diagnosis, On-site emergency treatment and In-hospital treatment, translocation of HS patients and prevention of HS.

Pattern of liver injury in adult patients with COVID-19: a retrospective analysis of 105 patients.

Abstract: Recent studies reported that patients with coronavirus disease-2019 (COVID-19) might have liver injury. However, few data on the combined analysis and change patterns of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBil) have been shown. This is a single-center retrospective study. A total of 105 adult patients hospitalized for confirmed COVID-19 in Beijing Ditan Hospital between January 12, and March 17, 2020 were included, and divided into mild group (n = 79) and severe group(n = 26). We compared liver functional test results between the two groups. Category of ALT change during the disease course was also examined. 56.2% (59/105) of the patients had unnormal ALT, AST, or total TBil throughout the course of the disease, but in 91.4% (96/105) cases the level of ALT, AST or TBil ≤3 fold of the upper limit of normal reference range (ULN). The overall distribution of ALT, AST, and TBil were all significantly difference between mild and severe group (P < 0.05). The percentage of the patients with elevated both ALT and AST was 12.7% (10/79) in mild cases vs. 46.2% (12/26) in severe cases (P = 0.001). 34.6% (9/26) severe group patients started to have abnormal ALT after admission, and 73.3% (77/105) of all patients had normal ALT before discharge. Elevated liver function index is very common in patients with COVID-19 infection, and the level were less than 3 × ULN, but most are reversible. The abnormality of 2 or more indexes is low in the patients with COVID-19, but it is more likely to occur in the severe group.

Role of adjunctive treatment strategies in COVID-19 and a review of international and national clinical guidelines.

Abstract: The coronavirus disease (COVID-19) pandemic has led to a global struggle to cope with the sheer numbers of infected persons, many of whom require intensive care support or eventually succumb to the illness. The outbreak is managed by a combination of disease containment via public health measures and supportive care for those who are affected. To date, there is no specific anti-COVID-19 treatment. However, the urgency to identify treatments that could turn the tide has led to the emergence of several investigational drugs as potential candidates to improve outcome, especially in the severe to critically ill. While many of these adjunctive drugs are being investigated in clinical trials, professional bodies have attempted to clarify the setting where the use of these drugs may be considered as off-label or compassionate use. This review summarizes the clinical evidence of investigational adjunctive treatments used in COVID-19 patients as well as the recommendations of their use from guidelines issued by international and national organizations in healthcare.

Hemostatic agents for prehospital hemorrhage control: a narrative review.

Abstract: Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma. A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival. A literature search was performed through PubMed, Scopus, and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents, prehospital, battlefield or combat dressings, and prehospital hemostatic resuscitation, followed by cross-reference searching. Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted. Based on these findings, this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings. These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action. Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.

Neuroregeneration and plasticity: a review of the physiological mechanisms for achieving functional recovery postinjury

Abstract: Neuronal networks, especially those in the central nervous system (CNS), evolved to support extensive functional capabilities while ensuring stability. Several physiological “brakes” that maintain the stability of the neuronal networks in a healthy state quickly become a hinderance postinjury. These “brakes” include inhibition from the extracellular environment, intrinsic factors of neurons and the control of neuronal plasticity. There are distinct differences between the neuronal networks in the peripheral nervous system (PNS) and the CNS. Underpinning these differences is the trade-off between reduced functional capabilities with increased adaptability through the formation of new connections and new neurons. The PNS has “facilitators” that stimulate neuroregeneration and plasticity, while the CNS has “brakes” that limit them. By studying how these “facilitators” and “brakes” work and identifying the key processes and molecules involved, we can attempt to apply these theories to the neuronal networks of the CNS to increase its adaptability. The difference in adaptability between the CNS and PNS leads to a difference in neuroregenerative properties and plasticity. Plasticity ensures quick functional recovery of abilities in the short and medium term. Neuroregeneration involves synthesizing new neurons and connections, providing extra resources in the long term to replace those damaged by the injury, and achieving a lasting functional recovery. Therefore, by understanding the factors that affect neuroregeneration and plasticity, we can combine their advantages and develop rehabilitation techniques. Rehabilitation training methods, coordinated with pharmacological interventions and/or electrical stimulation, contributes to a precise, holistic treatment plan that achieves functional recovery from nervous system injuries. Furthermore, these techniques are not limited to limb movement, as other functions lost as a result of brain injury, such as speech, can also be recovered with an appropriate training program.

Updating the diagnostic criteria of COVID-19 "suspected case" and "confirmed case" is necessary.

Abstract: On 6 February 2020, our team had published a rapid advice guideline for diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infection, and this guideline provided our experience and make well reference for fighting against this pandemic worldwide. However, the coronavirus disease 2019 (COVID-19) is a new disease, our awareness and knowledge are gradually increasing based on the ongoing research findings and clinical practice experience; hence, the strategies of diagnosis and treatment are also continually updated. In this letter, we answered one comment on our guideline and provided the newest diagnostic criteria of “suspected case” and “confirmed case” according to the latest Diagnosis and Treatment Guidelines for COVID-19 (seventh version) that issued by the National Health Committee of the People’s Republic of China.

Chitosan hydrogel encapsulated with LL-37 peptide promotes deep tissue injury healing in a mouse model

Abstract: LL-37 peptide is a member of the human cathelicidin family, and has been shown to promote the healing of pressure ulcers. However, the low stability of this peptide within the wound environment limits its clinical use. Chitosan (CS) hydrogel is commonly used as a base material for wound dressing material. CS hydrogel (2.5% w/v) was encapsulated with LL-37. Cytotoxicity of the product was examined in cultured NIH3T3 fibroblasts. Effects on immune response was examined by measuring tumor necrosis factor-α (TNF-α) release from RAW 264.7 macrophages upon exposure to lipopolysaccharides. Antibacterial activity was assessed using Staphylococcus aureus. Potential effect on pressure ulcers was examined using a mouse model. Briefly, adult male C57BL/6 mice were subjected to skin pressure using magnets under a 12/12 h schedule for 21 days. Mice were randomized to receive naked LL-37 (20 μg), chitosan gel containing 20-μg LL-37 (LL-37/CS hydrogel) or hydrogel alone under the ulcer bed (n = 6). A group of mice receiving no intervention was also included as a control. LL-37/CS hydrogel did not affect NIH3T3 cell viability. At a concentration of 1–5 μg/ml, LL-37/CS inhibited TNF-α release from macrophage. At 5 μg/ml, LL-37/CS inhibited the growth of Staphylococcus aureus. The area of the pressure ulcers was significantly lower in mice receiving LL-37/CS hydrogel in comparison to all other 3 groups on days 11 (84.24% ± 0.25%), 13 (56.22% ± 3.91%) and 15 (48.12% ± 0.28%). Histological examination on days 15 and 21 showed increased epithelial thickness and density of newly-formed capillary with naked LL-37 and more so with LL-37/CS. The expression of key macromolecules in the process of angiogenesis (i.e., hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor-A (VEGF-A)) in wound tissue was increased at both the mRNA and protein levels. Chitosan hydrogel encapsulated with LL-37 is biocompatible and could promote the healing of pressure ulcers.

Primary stratification and identification of suspected Corona virus disease 2019 (COVID-19) from clinical perspective by a simple scoring proposal.

Abstract: In this Commentary, we would like to comment on the article titled "A rapid advice guideline for the diagnosis and treatment of 2019 novel coronavirus (2019-nCoV) infected pneumonia (standard version)" as a featured article in Military Medical Research. In the guideline, except for "confirmed cases", "suspected cases", "close contact" and "suspicious exposure" were defined by clinical perspective based on epidemiological risk, clinical symptoms and auxiliary examination. Combined with our experience, we introduced a simple scoring proposal additionally based on not only CT imaging as strongly recommended by the guideline but also blood routine test, especially for primary screening of such patients in the out-patient department.

EPAS1 and VEGFA gene variants are related to the symptoms of acute mountain sickness in Chinese Han population: a cross-sectional study

Abstract: More people ascend to high altitude (HA) for various activities, and some individuals are susceptible to HA illness after rapidly ascending from plains. Acute mountain sickness (AMS) is a general complaint that affects activities of daily living at HA. Although genomic association analyses suggest that single nucleotide polymorphisms (SNPs) are involved in the genesis of AMS, no major gene variants associated with AMS-related symptoms have been identified. In this cross-sectional study, 604 young, healthy Chinese Han men were recruited in June and July of 2012 in Chengdu, and rapidly taken to above 3700 m by plane. Basic demographic parameters were collected at sea level, and heart rate, pulse oxygen saturation (SpO2), systolic and diastolic blood pressure and AMS-related symptoms were determined within 18–24 h after arriving in Lhasa. AMS patients were identified according to the latest Lake Louise scoring system (LLSS). Potential associations between variant genotypes and AMS/AMS-related symptoms were identified by logistic regression after adjusting for potential confounders (age, body mass index and smoking status). In total, 320 subjects (53.0%) were diagnosed with AMS, with no cases of high-altitude pulmonary edema or high-altitude cerebral edema. SpO2 was significantly lower in the AMS group than that in the non-AMS group (P = 0.003). Four SNPs in hypoxia-inducible factor-related genes were found to be associated with AMS before multiple hypothesis testing correction. The rs6756667 (EPAS1) was associated with mild gastrointestinal symptoms (P = 0.013), while rs3025039 (VEGFA) was related to mild headache (P = 0.0007). The combination of rs6756667 GG and rs3025039 CT/TT further increased the risk of developing AMS (OR = 2.70, P < 0.001). Under the latest LLSS, we find that EPAS1 and VEGFA gene variants are related to AMS susceptibility through different AMS-related symptoms in the Chinese Han population; this tool might be useful for screening susceptible populations and predicting clinical symptoms leading to AMS before an individual reaches HA. Chinese Clinical Trial Registration, ChiCTR-RCS-12002232 . Registered 31 May 2012.

Establishment and effectiveness evaluation of a scoring system for exertional heat stroke by retrospective analysis.

Abstract: Heat stroke (HS) is a serious, life-threatening disease. However, there is no scoring system for HS so far. This research is to establish a scoring system that can quantitatively assess the severity of exertional heat stroke (EHS). Data were collected from a total of 170 exertional heat stroke (EHS) patients between 2005 and 2016 from 52 hospitals in China. Univariate statistical methods and comparison of the area under the receiver operating characteristic (ROC) curve (AUC) were used to screen exertional heat stroke score (EHSS) parameters, including but not limited body temperature (T), Glasgow Coma Scale (GCS) and others. By comparing the sizes of the AUCs of the APACHE II, SOFA and EHSS assessments, the effectiveness of EHSS in evaluating the prognosis of EHS patients was verified. Through screening with a series of methods, as described above, the present study determined 12 parameters – body temperature (T), GCS, pH, lactate (Lac), platelet count (PLT), prothrombin time (PT), fibrinogen (Fib), troponin I (TnI), aspartate aminotransferase (AST), total bilirubin (TBIL), creatinine (Cr) and acute gastrointestinal injury (AGI) classification – as EHSS parameters. It is a 0–47 point system designed to reflect increasing severity of heat stroke. Low (EHSS 35) showed 100% survival and 100% mortality, respectively. We found that AUCEHSS > AUCSOFA > AUCAPACHE II. A total of 12 parameters – T, GCS, pH, Lac, PLT, PT, Fib, TnI, AST, TBIL, Cr and gastrointestinal AGI classification – are the EHSS parameters with the best effectiveness in evaluating the prognosis of EHS patients. As EHSS score increases, the mortality rate of EHS patients gradually increases.

Coronaviruses and gastrointestinal diseases.

Abstract: The effects of coronaviruses on the respiratory system are of great concern, but their effects on the digestive system receive much less attention. Coronaviruses that infect mammals have shown gastrointestinal pathogenicity and caused symptoms such as diarrhea and vomiting. Available data have shown that human coronaviruses, including the newly emerged SARS-CoV-2, mainly infect the respiratory system and cause symptoms such as cough and fever, while they may generate gastrointestinal symptoms. However, there is little about the relation between coronavirus and digestive system. This review specifically addresses the effects of mammalian and human coronaviruses, including SARS-CoV-2, on the digestive tract, helping to cope with the new virus infection-induced disease, COVID-19.

Models to predict injury, physical fitness failure and attrition in recruit training: a retrospective cohort study.

Abstract: Attrition rate in new army recruits is higher than in incumbent troops. In the current study, we identified the risk factors for attrition due to injuries and physical fitness failure in recruit training. A variety of predictive models were attempted. This retrospective cohort included 19,769 Army soldiers of the Australian Defence Force receiving recruit training during a period from 2006 to 2011. Among them, 7692 reserve soldiers received a 28-day training course, and the remaining 12,077 full-time soldiers received an 80-day training course. Retrieved data included anthropometric measures, course-specific variables, injury, and physical fitness failure. Multivariate regression was used to develop a variety of models to predict the rate of attrition due to injuries and physical fitness failure. The area under the receiver operating characteristic curve was used to compare the performance of the models. In the overall analysis that included both the 28-day and 80-day courses, the incidence of injury of any type was 27.8%. The 80-day course had a higher rate of injury if calculated per course (34.3% vs. 17.6% in the 28-day course), but lower number of injuries per person-year (1.56 vs. 2.29). Fitness test failure rate was significantly higher in the 28-day course (30.0% vs. 12.1%). The overall attrition rate was 5.2 and 5.0% in the 28-day and 80-day courses, respectively. Stress fracture was common in the 80-day course (n = 44) and rare in the 28-day course (n = 1). The areas under the receiver operating characteristic curves for the course-specific predictive models were relatively low (ranging from 0.51 to 0.69), consistent with “failed” to “poor” predictive accuracy. The course-combined models performed somewhat better than the course-specific models, with two models having AUC of 0.70 and 0.78, which are considered “fair” predictive accuracy. Attrition rate was similar between 28-day and 80-day courses. In comparison to the 80-day full course, the 28-day course had a lower rate of injury but a higher number of injuries per person-year and of fitness test failure. These findings suggest fitness level at the commencement of training is a critically important factor to consider when designing the course curriculum, particularly short courses.

Direct conversion of human fibroblasts into dopaminergic neuron-like cells using small molecules and protein factors

Abstract: Generation of neurons is essential in cell replacement therapy for neurodegenerative disorders like Parkinson’s disease. Several studies have reported the generation of dopaminergic (DA) neurons from mouse and human fibroblasts by ectopic expression of transcription factors, in which genetic manipulation is associated with potential risks. The small molecules and protein factors were selected based on their function to directly induce human fetal lung IMR-90 fibroblasts into DA neuron-like cells. Microscopical, immunocytochemical, and RT-qPCR analyses were used to characterize the morphology, phenotype, and gene expression features of the induced cells. The whole-cell patch-clamp recordings were exploited to measure the electrophysiological properties. Human IMR-90 fibroblasts were rapidly converted into DA neuron-like cells after the chemical induction using small molecules and protein factors, with a yield of approximately 95% positive TUJ1-positive cells. The induced DA neuron-like cells were immunopositive for pan-neuronal markers MAP2, NEUN, and Synapsin 1 and DA markers TH, DDC, DAT, and NURR1. The chemical induction process did not involve a neural progenitor/stem cell intermediate stage. The induced neurons could fire single action potentials, which reflected partially the electrophysiological properties of neurons. We developed a chemical cocktail of small molecules and protein factors to convert human fibroblasts into DA neuron-like cells without passing through a neural progenitor/stem cell intermediate stage. The induced DA neuron-like cells from human fibroblasts might provide a cellular source for cell-based therapy of Parkinson’s disease in the future.

Sequential intraventricular injection of tigecycline and polymyxin B in the treatment of intracranial Acinetobacter baumannii infection after trauma: a case report and review of the literature.

Abstract: Intracranial infection after craniotomy is one of the most serious postoperative complications, especially multidrug-resistant (MDR) or extensively drug-resistant (XDR) bacterial meningitis, and strongly affects the prognosis of patients. Current treatment experience regarding these infections is scarce. We report a case of severe intracranial infection of XDR Acinetobacter baumannii (A. baumannii) that was treated by intravenous (IV) injection, sequential intraventricular (IVT) injection of tigecycline and polymyxin B, and other anti-infective drugs. Good results were obtained, and the patient was eventually discharged from the hospital. This case is characterized by intracranial infection. The polymyxin B IV + IVT pathway is an ideal treatment strategy for XDR A. baumannii. The tigecycline IVT pathway is also a safe treatment option.

Sleep disturbances and predictors of nondeployability among active-duty Army soldiers: an odds ratio analysis of medical healthcare data from fiscal year 2018

Abstract: The impact of sleep disorders on active-duty soldiers’ medical readiness is not currently quantified. Patient data generated at military treatment facilities can be accessed to create research reports and thus can be used to estimate the prevalence of sleep disturbances and the role of sleep on overall health in service members. The current study aimed to quantify sleep-related health issues and their impact on health and nondeployability through the analysis of U.S. military healthcare records from fiscal year 2018 (FY2018). Medical diagnosis information and deployability profiles (e-Profiles) were queried for all active-duty U.S. Army patients with a concurrent sleep disorder diagnosis receiving medical care within FY2018. Nondeployability was predicted from medical reasons for having an e-Profile (categorized as sleep, behavioral health, musculoskeletal, cardiometabolic, injury, or accident) using binomial logistic regression. Sleep e-Profiles were investigated as a moderator between other e-Profile categories and nondeployability. Out of 582,031 soldiers, 48.4% (n = 281,738) had a sleep-related diagnosis in their healthcare records, 9.7% (n = 56,247) of soldiers had e-Profiles, and 1.9% (n = 10,885) had a sleep e-Profile. Soldiers with sleep e-Profiles were more likely to have had a motor vehicle accident (pOR (prevalence odds ratio) =4.7, 95% CI 2.63–8.39, P ≤ 0.001) or work/duty-related injury (pOR = 1.6, 95% CI 1.32–1.94, P ≤ 0.001). The likelihood of nondeployability was greater in soldiers with a sleep e-Profile and a musculoskeletal e-Profile (pOR = 4.25, 95% CI 3.75–4.81, P ≤ 0.001) or work/duty-related injury (pOR = 2.62, 95% CI 1.63–4.21, P ≤ 0.001). Nearly half of soldiers had a sleep disorder or sleep-related medical diagnosis in 2018, but their sleep problems are largely not profiled as limitations to medical readiness. Musculoskeletal issues and physical injury predict nondeployability, and nondeployability is more likely to occur in soldiers who have sleep e-Profiles in addition to these issues. Addressing sleep problems may prevent accidents and injuries that could render a soldier nondeployable.

Does the preoperative platelet-to-lymphocyte ratio and neutrophil-to-lymphocyte ratio predict morbidity after gastrectomy for gastric cancer?

Abstract: Gastric cancer is the 2nd most common cause of cancer-related deaths, and the morbidity rate after surgery is reported to be as high as 46%. The estimation of possible complications, morbidity, and mortality and the ability to specify patients at high risk have become substantial for an intimate follow-up and for proper management in the intensive care unit. This study aimed to determine the prognostic value of the preoperative platelet-to-lymphocyte ratio (PLR) and neutrophil-to-lymphocyte ratio (NLR) and their relations with clinical outcomes and complications after gastrectomy for gastric cancer. This single-center, retrospective cohort study evaluated the data of 292 patients who underwent gastrectomy with curative intent between January 2015 and June 2018 in a tertiary state hospital in Ankara, Turkey. A receiver operating characteristic curve was generated to evaluate the ability of laboratory values to predict clinically relevant postoperative complications. The area under the curve was computed to compare the predictive power of the NLR and PLR. Then, the cutoff points were selected as the stratifying values for the PLR and NLR. The area under the curve values of the PLR (0.60, 95% CI 0.542–0.657) and NLR (0.556, 95% CI 0.497–0.614) were larger than those of the other preoperative laboratory values. For the PLR, the diagnostic sensitivity and specificity were 50.00 and 72.22%, respectively, whereas for the NLR, the diagnostic sensitivity and specificity were 37.50 and 80.16%, respectively. The PLR was related to morbidity, whereas the relation of the NLR with mortality was more prominent. This study demonstrated that the PLR and NLR may predict mortality and morbidity via the Clavien-Dindo classification in gastric cancer patients. The variable was grade ≥ 3 in the Clavien-Dindo classification, including complications requiring surgical or endoscopic interventions, life-threatening complications, and death. Both the PLR and NLR differed significantly according to Clavien-Dindo grade ≥ 3. In this analysis, the PLR was related to morbidity, while the NLR relation with mortality was more intense. Based on the results of the study, the PLR and NLR could be used as independent predictive factors for mortality and morbidity in patients with gastric cancer.

Effects of Mycobacterium vaccae vaccine in a mouse model of tuberculosis: protective action and differentially expressed genes.

Abstract: Tuberculosis is a leading cause of death worldwide. BCG is an effective vaccine, but not widely used in many parts of the world due to a variety of issues. Mycobacterium vaccae (M. vaccae) is another vaccine used in human subjects to prevent tuberculosis. In the current study, we investigated the potential mechanisms of M. vaccae vaccination by determining differentially expressed genes in mice infected with M. tuberculosis before and after M. vaccae vaccination. Three days after exposure to M. tuberculosis H37Rv strain (5 × 105 CFU), adult BALB/c mice randomly received either M. vaccae vaccine (22.5 μg) or vehicle via intramuscular injection (n = 8). Booster immunization was conducted 14 and 28 days after the primary immunization. Differentially expressed genes were identified by microarray followed by standard bioinformatics analysis. M. vaccae vaccination provided protection against M. tuberculosis infection (most prominent in the lungs). We identified 2326 upregulated and 2221 downregulated genes in vaccinated mice. These changes could be mapped to a total of 123 signaling pathways (68 upregulated and 55 downregulated). Further analysis pinpointed to the MyD88-dependent TLR signaling pathway and PI3K-Akt signaling pathway as most likely to be functional. M. vaccae vaccine provided good protection in mice against M. tuberculosis infection, via a highly complex set of molecular changes. Our findings may provide clue to guide development of more effective vaccine against tuberculosis.

Association between physiological responses after exercise at low altitude and acute mountain sickness upon ascent is sex-dependent

Abstract: Acute mountain sickness (AMS) is the mildest form of acute altitude illnesses, and consists of non-specific symptoms when unacclimatized persons ascend to elevation of ≥2500 m. Risk factors of AMS include: the altitude, individual susceptibility, ascending rate and degree of pre-acclimatization. In the current study, we examined whether physiological response at low altitude could predict the development of AMS. A total of 111 healthy adult healthy volunteers participated in this trial; and 99 (67 men and 32 women) completed the entire study protocol. Subjects were asked to complete a 9-min exercise program using a mechanically braked bicycle ergometer at low altitude (500 m). Heart rate, blood pressure (BP) and pulse oxygen saturation (SpO2) were recorded prior to and during the last minute of exercise. The ascent from 500 m to 4100 m was completed in 2 days. AMS was defined as ≥3 points in a 4-item Lake Louise Score, with at least one point from headache wat 6–8 h after the ascent. Among the 99 assessable subjects, 47 (23 men and 24 women) developed AMS at 4100 m. In comparison to the subjects without AMS, those who developed AMS had lower proportion of men (48.9% vs. 84.6%, P < 0.001), height (168.4 ± 5.9 vs. 171.3 ± 6.1 cm, P = 0.019), weight (62.0 ± 10.0 vs. 66.7 ± 8.6 kg, P = 0.014) and proportion of smokers (23.4% vs. 51.9%, P = 0.004). Multivariate regression analysis revealed the following independent risks for AMS: female sex (odds ratio (OR) =6.32, P < 0.001), SpO2 change upon exercise at low altitude (OR = 0.63, P = 0.002) and systolic BP change after the ascent (OR = 0.96, P = 0.029). Women had larger reduction in SpO2 after the ascent, higher AMS percentage and absolute AMS score. Larger reduction of SpO2 after exercise was associated with both AMS incidence (P = 0.001) and AMS score (P < 0.001) in men but not in women. Larger SpO2 reduction after exercise at low altitude was an independent risk for AMS upon ascent. Such an association was more robust in men than in women. Chinese Clinical Trial Registration, ChiCTR1900025728 . Registered 6 September 2019.

The impacts of infectious complications on outcomes in acute pancreatitis: a retrospective study

Abstract: The occurrence of infectious complications characterizes the more severe forms of acute pancreatitis (AP) and is associated with high mortality. We investigated the effects of infection at different sites in patients with AP, including those with necrotizing pancreatitis (NP). We conducted a retrospective analysis of 285 patients who met the inclusion criteria for AP and were admitted to Tianjin Nankai Hospital between January 2016 and September 2019. According to the source of the culture positivity during hospitalization, patients were divided into four groups: sterile group(n = 148), pancreatic infection group(n = 65), extrapancreatic infection group(n = 22) and combined infection group(n = 50). The source of infection, microbiology, biochemical parameters and prognostic indicators were analyzed. In terms of baseline characteristics, the four groups were similar in age, sex, aetiology, previous pancreatitis and diabetes. Compared with the severity of the disease in the other groups, the APACHE II scores(9.91 ± 4.65, 9.46 ± 5.05, respectively) and organ failure rate (40.9 and 50%, respectively)were higher in the extrapancreatic infection group and the combined infection group (P < 0.05). The frequency of surgical intervention and hospitalization time in patients with NP complicated with extrapancreatic infection was greatly increased (P < 0.05). Regarding the primary outcome, patients in the combined infection group had longer hospital stays (68.28 ± 51.80 vs 55.58 ± 36.24, P < 0.05) and higher mortality (24.0% vs 9.2%, P < 0.05) than patients in the pancreatic infection group. In addition, patients in the extrapancreatic infection group also showed high intensive care utilization (59.1%) and mortality rates (18.2%). Among the 137 AP patients with infection complications, 89 patients exhibited multidrug-resistant (MDR) microorganisms, and the mortality rate of patients with MDR bacterial infection was higher than that of patients with non-MDR bacterial infection (24.7% vs 3.6%, P = 0.001). Clinicians should be aware that extrapancreatic infection (EPI) significantly aggravates the main outcome in pancreatic infection patients. Infection with MDR bacteria is also associated with AP mortality.

Methods for improving thermal tolerance in military personnel prior to deployment.

Abstract: Acute exposure to heat, such as that experienced by people arriving into a hotter or more humid environment, can compromise physical and cognitive performance as well as health. In military contexts heat stress is exacerbated by the combination of protective clothing, carried loads, and unique activity profiles, making them susceptible to heat illnesses. As the operational environment is dynamic and unpredictable, strategies to minimize the effects of heat should be planned and conducted prior to deployment. This review explores how heat acclimation (HA) prior to deployment may attenuate the effects of heat by initiating physiological and behavioural adaptations to more efficiently and effectively protect thermal homeostasis, thereby improving performance and reducing heat illness risk. HA usually requires access to heat chamber facilities and takes weeks to conduct, which can often make it impractical and infeasible, especially if there are other training requirements and expectations. Recent research in athletic populations has produced protocols that are more feasible and accessible by reducing the time taken to induce adaptations, as well as exploring new methods such as passive HA. These protocols use shorter HA periods or minimise additional training requirements respectively, while still invoking key physiological adaptations, such as lowered core temperature, reduced heart rate and increased sweat rate at a given intensity. For deployments of special units at short notice (< 1 day) it might be optimal to use heat re-acclimation to maintain an elevated baseline of heat tolerance for long periods in anticipation of such an event. Methods practical for military groups are yet to be fully understood, therefore further investigation into the effectiveness of HA methods is required to establish the most effective and feasible approach to implement them within military groups.

Practice parameters for the use of actigraphy in the military operational context: the Walter Reed Army Institute of Research Operational Research Kit-Actigraphy (WORK-A)

Abstract: The Walter Reed Army Institute of Research (WRAIR) Operational Research Kit-Actigraphy (WORK-A) is a set of unique practice parameters and actigraphy-derived measures for the analysis of operational military sleep patterns The WORK-A draws on best practices from the literature and comprises 15 additional descriptive variables Here, we demonstrate the WORK-A with a sample of United States Army Reserve Officers’ Training Corps (ROTC) cadets (n = 286) during a month-long capstone pre-commissioning training exercise The sleep of ROTC cadets (n = 286) was measured by Philips Actiwatch devices during the 31-day training exercise The preliminary effectiveness of the WORK-A was tested by comparing differences in sleep measures collected by Actiwatches as calculated by Philips Actiware software against WORK-A-determined sleep measures and self-report sleep collected from a subset of ROTC cadets (n = 140) Actiware sleep summary statistics were significantly different from WORK-A measures and self-report sleep (all P ≤ 0001) Bedtimes and waketimes as determined by WORK-A major sleep intervals showed the best agreement with self-report bedtime (22:21 ± 1:30 vs 22:13 ± 0:40, P = 021) and waketime (04:30 ± 2:17 vs 04:31 ± 0:47, P = 068) Though still significantly different, the discrepancy was smaller between the WORK-A measure of time in bed (TIB) for major sleep intervals (352 ± 29 min) and self-report nightly sleep duration (337 ± 57 min, P = 0006) than that between the WORK-A major TIB and Actiware TIB (177 ± 42, P ≤ 0001) Default actigraphy methods are not the most accurate methods for characterizing soldier sleep, but reliable methods for characterizing operational sleep patterns is a necessary first step in developing strategies to improve soldier readiness The WORK-A addresses this knowledge gap by providing practice parameters and a robust variety of measures with which to profile sleep behavior in service members

Circadian misalignment on submarines and other non-24-h environments - from research to application.

Abstract: Circadian clocks have important physiological and behavioral functions in humans and other organisms, which enable organisms to anticipate and respond to periodic environmental changes. Disturbances in circadian rhythms impair sleep, metabolism, and behavior. People with jet lag, night workers and shift workers are vulnerable to circadian misalignment. In addition, non-24-h cycles influence circadian rhythms and cause misalignment and disorders in different species, since these periods are beyond the entrainment ranges. In certain special conditions, e.g., on submarines and commercial ships, non-24-h watch schedules are often employed, which have also been demonstrated to be deleterious to circadian rhythms. Personnel working under such conditions suffer from circadian misalignment with their on-watch hours, leading to increased health risks and decreased cognitive performance. In this review, we summarize the research progress and knowledge concerning circadian rhythms on submarines and other environments in which non-24-h watch schedules are employed.

Mental health status in veterans residing in rural versus non-rural areas: results from the veterans' health study.

Abstract: The majority of Veterans Affair (VA) hospitals are in urban areas. We examined whether veterans residing in rural areas have lower mental health service use and poorer mental health status. Veterans with at least 1 warzone deployment in central and northeastern Pennsylvania were randomly selected for an interview. Mental health status, including PTSD, major depression, alcohol abuse and mental health global severity, were assessed using structured interviews. Psychiatric service use was based on self-reported utilization in the past 12 months. Results were compared between veterans residing in rural and non-rural areas. Data were also analyzed using multivariate logistic regression to minimize the influence by confounding factors. A total of 1730 subjects (55% of the eligible veterans) responded to the survey and 1692 of them had complete geocode information. Those that did not have this information (n = 38), were excluded from some analyses. Veterans residing in rural areas were older, more often of the white race, married, and experienced fewer stressful events. In comparison to those residing in non-rural areas, veterans residing in rural areas had lower global mental health severity scores; they also had fewer mental health visits. In multivariate logistic regression, rural residence was associated with lower service use, but not with PTSD, major depression, alcohol abuse, and global mental health severity score after adjusting confounding factors (e.g., age, gender, marital status and education). Rural residence is associated with lower mental health service use, but not with poor mental health in veterans with former warzone deployment, suggesting rural residence is possibly protective.