Abstract:Background:Pre-exposure prophylaxis (PrEP) prevents human immunodeficiency virus (HIV) infection, but its use remains low among U.S. military men who have sex with men (MSM), likely due to mis-matching with personal preferences. We conducted a study to characterize preferences to PrEP measures within this population.Methods:HIV-negative military MSM were recruited through a closed, Lesbian, Gay, Bisexual, and Transgendered (LGBT) military social media group. The survey was anonymous, and consisted of five experimentally varied attributes in service delivery: dosing method, provider type, visit location, lab work evaluation location, and dispensing venue. Relative importance and part-worth utility scores were generated using hierarchical bayes (HB) estimation, and the randomized first choice model was used to examine participation interest across eight possible PrEP program scenarios.Results:A total of 429 participants completed the survey. Among the eight scenarios with varying attributes, the most preferred scenario featured a daily tablet, PrEP injection or implant, along with a military provider, smartphone/telehealth visit, and on-base locations for lab evaluation and medication pick-up. The results also emphasized the importance for providers to be familiar with PrEP prescription knowledge, and to provide interactions sensitive to sexual identity and mental health.Conclusions:A PrEP program consisting of daily tablet is preferred in military healthcare settings is preferred. Long-acting implants and injections are also desired.
Abstract:Background:The vital signs of trauma patients are complex and changeable, and the prediction of blood transfusion demand mainly depends on doctors’ experience and trauma scoring system; therefore, it cannot be accurately predicted. In this study, a machine learning decision tree algorithm [classification and regression tree (CRT) and eXtreme gradient boosting (XGBoost)] was proposed for the demand prediction of traumatic blood transfusion to provide technical support for doctors.Methods:A total of 1371 trauma patients who were diverted to the Emergency Department of the First Medical Center of Chinese PLA General Hospital from January 2014 to January 2018 were collected from an emergency trauma database. The vital signs, laboratory examination parameters and blood transfusion volume were used as variables, and the non-invasive parameters and all (non-invasive + invasive) parameters were used to construct an intelligent prediction model for red blood cell (RBC) demand by logistic regression (LR), CRT and XGBoost. The prediction accuracy of the model was compared with the area under curve (AUC).Results:For non-invasive parameters, the LR method was the best, with an AUC of 0.72 [95% confidence interval (CI) 0.657–0.775], which was higher than the CRT (AUC 0.69, 95%CI 0.633–0.751) and the XGBoost (AUC 0.71, 95%CI 0.654–0.756)(P<0.05). The trauma location and shock index are important prediction parameters. For all the prediction parameters, XGBoost was the best, with an AUC of 0.94 (95%CI 0.893–0.981), which was higher than the LR (AUC 0.80, 95%CI 0.744–0.850) and the CRT (AUC 0.82, 95%CI 0.779–0.853)(P<0.05). Haematocrit (Hct) is an important prediction parameter.Conclusions:The classification performance of the intelligent prediction model of red blood cell transfusion in trauma patients constructed by the decision tree algorithm is not inferior to that of the traditional LR method. It can be used as a technical support to assist doctors to make rapid and accurate blood transfusion decisions in emergency rescue environment, so as to improve the success rate of patient treatment.
Abstract:Background:The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis (TB) effects. The anti-TB effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH.Methods:BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, TB model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an enzyme-linked immunospot assay (ELISPOT), and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing.Results:After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P<0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P<0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P<0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model.Conclusions:NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.
Keywords:Traditional Chinese medicine;Tuberculosis;NiuBeiXiaoHe extract;JieHeWan;Therapeutic effect
Abstract:Background:An adequate hydration status is critical to ensure efficiency during mental and physical activities. Our goal was to assess the hydration status of a Spanish group of aeronautical military men and to determine the association of hydration status with body composition and anxiety.Methods:A total of 188 men were evaluated through a validated hydration questionnaire, anthropometric and biochemical parameters, and an anxiety questionnaire. Based on these methods, the criteria of hydration were established.Results:Of the total sample, 81% met the hydration criteria (urine color = well hydrated, water balance ≥0 ml, and total water intake/weight ≥35 ml/kg), and 19% did not meet the hydration criteria (urine color = not sufficiently hydrated or dehydrated, water balance <0 ml, and total water intake/weight <35 ml/kg). Subjects not meeting the hydration criteria had lower urine pH, negative water balance, and lower water intake. The latter also had higher anxiety status (score=4 vs. 3, P=0.026), weight [(84.7±10.5) kg vs. (80.5±10.2) kg], body mass index [(26.3±3.1) kg/m2 vs. (25.2±2.8) kg/m2], body fat [(22.3±5.6)% vs. (18.3±6.5)%], urine specific gravity, and urine color. Using a logistic binary regression model, hydration status was related significantly with the percentage of body fat (P=0.004), but no relation was found with age, comorbidities, or medications. Furthermore, total water intake/weight was positively correlated with percentage of body water (r=0.357, P=0.000) and negatively with body fat (kg) (r=–0.427, P=0.000), percentage of body fat (r=–0.405, P=0.000), and waist/ hip ratio (r=–0.223, P=0.002). Based on a linear regression model, total water intake/weight was related significantly with percentage of body fat (P=0.001) and percentage of body water content (P=0.035). No relation was found, however, with waist/hip ratio, age, comorbidities, or medications.Conclusions:These findings all suggest a relationship between hydration status and body composition but also set the bases for future studies that relate hydration status and anxiety status. These results can be used to improve the hydration status and body composition of military personnel.
Abstract:Background:Fluid overload (FO) after resuscitation is frequent and contributes to adverse outcomes among postinjury open abdomen (OA) patients. Bioelectrical impedance analysis (BIA) is a promising tool for monitoring fluid status and FO. Therefore, we sought to investigate the efficacy of BIA-directed fluid resuscitation among OA patients.Methods:A pragmatic, prospective, randomized, observer-blind, single-center trial was performed for all trauma patients requiring OA between January 2013 and December 2017 to a national referral center. A total of 140 postinjury OA patients were randomly assigned in a 1:1 ratio to receive either a BIA-directed fluid resuscitation (defined as BIA) protocol that included fluid administration with monitoring of hemodynamic parameters and different degrees of interventions to achieve a negative fluid balance targeting the hydration level (HL) measured by BIA or a traditional fluid resuscitation (TRD) in which clinicians determined the fluid resuscitation regimen according to traditional parameters during 30 d of intensive care unit (ICU) management. The primary outcome was the 30-day primary fascial closure (PFC) rate. The secondary outcomes included the time to PFC, postoperative 7-day cumulative fluid balance (CFB) and adverse events within 30 d after OA. The Kaplan–Meier method and the log-rank test were utilized for PFC after OA. A generalized linear regression model for the time to PFC and CFB was built.Results:A total of 134 patients completed the trial (BIA, n=66; TRD, n=68). The BIA patients were significantly more likely to achieve PFC than the TRD patients (83.33% vs. 55.88%, P<0.001). In the BIA group, the time to PFC occurred earlier than that of the TRD group by an average of 3.66 d (P<0.001). Additionally, the BIA group showed a lower postoperative 7-day CFB by an average of 6632.80 ml (P<0.001) and fewer complications.Conclusions:Among postinjury OA patients in the ICU, the use of BIA-guided fluid resuscitation resulted in a higher PFC rate and fewer severe complications than the traditional fluid resuscitation strategy.
Abstract: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.
Keywords:malondialdehyde;Oxidative stress;Free radical;Gulf War veterans;Gulf war illness;Pesticide
Abstract: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.
Abstract:The management of bacterial infections is becoming a major clinical challenge due to the rapid evolution of antibiotic resistant bacteria. As an excellent candidate to overcome antibiotic resistance, antimicrobial peptides (AMPs) that are produced from the synthetic and natural sources demonstrate a broad-spectrum antimicrobial activity with the high specificity and low toxicity. These peptides possess distinctive structures and functions by employing sophisticated mechanisms of action. This comprehensive review provides a broad overview of AMPs from the origin, structural characteristics, mechanisms of action, biological activities to clinical applications. We finally discuss the strategies to optimize and develop AMP-based treatment as the potential antimicrobial and anticancer therapeutics.
Keywords:Antimicrobial peptides;Antimicrobial resistance;Mechanism of action;Biological activity;Clinical application
Abstract: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.
Abstract:Retinoic acid-inducible gene I (RIG-I) and melanoma differentiation-associated protein 5 (MDA5) sense viral RNA and activate antiviral immune responses. Herein we investigate their functions in human epithelial cells, the primary and initial target of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). A deficiency in MDA5, RIG-I or mitochondrial antiviral signaling protein (MAVS) enhanced viral replication. The expression of the type I/III interferon (IFN) during infection was impaired in MDA5–/– and MAVS–/–, but not in RIG-I–/–, when compared to wild type (WT) cells. The mRNA level of full-length angiotensin-converting enzyme 2 (ACE2), the cellular entry receptor for SARS-CoV-2, was approximately 2.5-fold higher in RIG-I–/– than WT cells. These data demonstrate MDA5 as the predominant SARS-CoV-2 sensor, IFN-independent induction of ACE2 and anti-SARS-CoV-2 role of RIG-I in epithelial cells.
Keywords:Severe acute respiratory syndrome coronavirus 2;Pathogen pattern recognition receptor;Melanoma differentiation-associated protein 5;Retinoic acid-inducible gene I