Identifying significant correlates of purpose in life in older US military veterans: results from the national health and resilience in veterans study.

OBJECTIVE: Perceived purpose in life (PIL) has been linked to a broad range of adverse physical, mental, and cognitive outcomes. However, limited research has examined factors associated with PIL that can be targeted in prevention and treatment efforts in aging populations at heightened risk of adverse outcomes. Using data from predominantly older US veterans, we sought to identify important correlates of PIL. METHODS: Cross-sectional data were analyzed from the 2019-2020 National Health and Resilience in Veterans Study, which surveyed a nationally representative sample of 4069 US military veterans (Mage = 62.2). Elastic net and relative importance analyses were conducted to evaluate sociodemographic, military, health, and psychosocial variables that were strongly associated with PIL. RESULTS: Of the 39 variables entered into an elastic net analysis, 10 were identified as significant correlates of PIL. In order of magnitude, these were resilience (18.7% relative variance explained [RVE]), optimism (12.1%), depressive symptoms (11.3%), community integration (10.7%), gratitude (10.2%), loneliness (9.8%), received social support (8.6%), conscientiousness (8.5%), openness to experience (5.4%), and intrinsic religiosity (4.7%). CONCLUSIONS: Several modifiable psychosocial factors emerged as significant correlates of PIL in US military veterans. Interventions designed to target these factors may help increase PIL and mitigate risk for adverse health outcomes in this population.

Occupational exposures to airborne per- and polyfluoroalkyl substances (PFAS)-A review.

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are a group of synthetically-made chemicals with diverse functional properties that have become ubiquitous in our environment because of their widespread use. PFAS exposure has been associated with adverse health effects, and it is therefore vital to know how exposure may occur. Many studies have focused on environmental exposure from drinking water, but there is a paucity of data on inhalation exposure, especially in occupational settings. METHODS: In this study, through a comprehensive literature search, measured airborne (i.e., aerosols, volatiles, and dust) inhalation exposure and area levels were compiled for various occupations to compare reported levels of PFAS exposure. Airborne PFAS levels measured in various occupations such as ski waxing, textile manufacturing, firefighting, and floor waxing were analyzed and compared. RESULTS: Results of this review demonstrate that workers experience varying levels of PFAS exposure contingent on the workplace and industry and the work tasks performed within the workplace. Out of all occupations, ski waxing exhibited the highest total PFAS airborne concentrations when compared to all other reported occupational and residential exposures. CONCLUSIONS: Further research is recommended to estimate the risk of PFAS exposures in the occupations reviewed and to identify other potential occupations at risk of PFAS exposure. In addition, informed recommendations to implement safety measures ought to be developed to protect workers from adverse health effects.

Occupational exposure and serum levels of per- and polyfluoroalkyl substances (PFAS): A review.

BACKGROUND: Per- and polyfluoroalkyl substances, or PFAS, are a class of chemicals used in nearly all sectors of industry and many consumer products. Their resistance to degradation, however, means that PFAS are ubiquitous in the environment and bioaccumulate. PFAS exposure has also been linked to a variety of adverse health effects. Occupational PFAS exposure is of particular concern as research on PFAS exposure in worker populations has historically been limited and generally restricted to fluorochemical plant workers involved in PFAS production. METHODS: A comprehensive review of peer-reviewed scientific literature was conducted to investigate which worker populations may experience occupational exposure to PFAS. Serum PFAS levels reported in various occupations were analyzed and compared to serum PFAS levels published on the general public exposed to PFAS-contaminated drinking water and the study population of the National Health and Nutrition Examination Survey (NHANES). RESULTS: Our analysis indicates that professional ski waxers and firefighters may be exposed to several different PFAS at levels often similar to or higher than levels among fluorochemical plant workers and individuals in communities with PFAS-contaminated drinking water, and higher than levels in the general public. PFAS serum level data on other occupations were largely absent. CONCLUSIONS: Results highlight a need for additional research on occupational PFAS exposures and concomitant environmental exposures in these populations. Research on exposure levels in occupations and industries known or suspected to utilize PFAS is critically needed to foster informed recommendations for exposure mitigation measures to protect workers from adverse health effects of PFAS exposure.

Zika Virus Infection in the Developing Mouse Produces Dramatically Different Neuropathology Dependent on Viral Strain.

Zika virus (ZIKV) infection during pregnancy has been causally linked to a constellation of neurodevelopmental deformities in the fetus resulting in a disease termed congenital Zika syndrome (CZS). Here we detail how ZIKV infection produces extensive neuropathology in the developing mouse brain and spinal cord of both sexes. Surprisingly, neuropathology differs depending on viral strain with a French Polynesian isolate producing primarily excitotoxicity and a Brazilian isolate being almost exclusively apoptotic but occurring over a prolonged period that is more likely to produce severe hypoplasia. We also show exposure can produce a characteristic pattern of infection that mirrors neuropathology and ultimately results in gross morphological deformities strikingly similar to CZS. This research provides a valuable mouse model mirroring the clinical course of disease that can be used to test potential therapies to improve treatment and gain a better understanding of the disabilities associated with CZS.SIGNIFICANCE STATEMENT Zika virus (ZIKV) infection during pregnancy has been causally linked to a constellation of neurodevelopmental deformities in the fetus resulting in a disease termed congenital Zika syndrome. Despite its devastating effects, very little is known about how ZIKV infection produces fetal neuropathology. Here we detail the temporal progression of ZIKV infection in the mouse brain and spinal cord resulting in massive neurodegeneration of infected regions. We also report a ZIKV strain from a region of Brazil with high levels of microcephaly (abnormally small head circumference) produces particularly devastating neuropathology.

Stress and coping strategies among nursing students: an international study.

BACKGROUND: Mounting literature on stress and coping in nursing students are available; however, most of the findings are confined to a single cultural group. AIMS: This study was conducted to determine the level of stress, its sources and coping strategies among nursing students from three countries: Greece, the Philippines and Nigeria. METHODS: Using a descriptive, comparative research design, 547 nursing students (161 Greek nursing students, 153 Filipino nursing students, 233 Nigerian nursing students) participated in the study from August 2015 to April 2016. Two standardized instruments were used, the Perceived Stress Scale (PSS) and the Coping Behavior Inventory (CBI). RESULTS: Findings revealed that the degree of stress and the type of stressors and coping styles utilized by nursing students differ according to the country of origin. The year of study predicted overall stress (ß = -0.149, p < 0.001) while advanced age predicted overall coping (ß = 0.008, p = 0.037) in the nursing students. CONCLUSIONS: Strengthening nursing students' positive coping skills may be helpful for them to effectively deal with various stressors during their educational experiences while maximizing learning. Implementing empirically tested approaches maybe useful to prevent the recurrence of stress and lessen its impact such as stress management counseling, counseling programs, establishing peer and family support systems, and formulating hospital policies that will support nursing students.

Versatile, mild, and selective reduction of various carbonyl groups using an electron-deficient boron catalyst.

A mild and selective new method was discovered to reduce acetanilides and other carbonyl compounds. Unlike sodium borohydride, which is selective in reducing aldehydes and ketones, this new protocol is uniquely selective in reducing acetanilides and nitriles over other carbonyl containing functional groups. Additionally, ß-ketoamides were shown to be reduced at the ketone preferentially over the amide.

Impact of Vasodilation on Oxygen-Enhanced Functional Lung MRI at 0.55 T.

BACKGROUND: Oxygen-enhanced magnetic resonance imaging (OE-MRI) can be used to assess regional lung function without ionizing radiation. Inhaled oxygen acts as a T1-shortening contrast agent to increase signal in T1-weighted (T1w) images. However, increase in proton density from pulmonary hyperoxic vasodilation may also contribute to the measured signal enhancement. Our aim was to quantify the relative contributions of the T1-shortening and vasodilatory effects of oxygen to signal enhancement in OE-MRI in both swine and healthy volunteers. METHODS: We imaged 14 anesthetized female swine (47 ± 8 kg) using a prototype 0.55 T high-performance MRI system while experimentally manipulating oxygenation and blood volume independently through oxygen titration, partial occlusion of the vena cava for volume reduction, and infusion of colloid fluid (6% hydroxyethyl starch) for volume increase. Ten healthy volunteers were imaged before, during, and after hyperoxia. Two proton density-weighted (PDw) and 2 T1w ultrashort echo time images were acquired per experimental state. The median PDw and T1w percent signal enhancement (PSE), compared with baseline room air, was calculated after image registration and correction for lung volume changes. Differences in median PSE were compared using Wilcoxon signed rank test. RESULTS: The PSE in PDw images after 100% oxygen was similar in swine (1.66% ± 1.41%, P = 0.01) and in healthy volunteers (1.99% ± 1.79%, P = 0.02), indicating that oxygen-induced pulmonary vasodilation causes ~2% lung proton density increase. The PSE in T1w images after 100% oxygen was also similar (swine, 9.20% ± 1.68%, P < 0.001; healthy volunteers, 10.10% ± 3.05%, P < 0.001). The PSE in T1w enhancement was oxygen dose-dependent in anesthetized swine, and we measured a dose-dependent PDw image signal increase from infused fluids. CONCLUSIONS: The contribution of oxygen-induced vasodilation to T1w OE-MRI signal was measurable using PDw imaging and was found to be ~2% in both anesthetized swine and in healthy volunteers. This finding may have implications for patients with regional or global hypoxia or vascular dysfunction undergoing OE-MRI and suggest that PDw imaging may be useful to account for oxygen-induced vasodilation in OE-MRI.

Implementing practice guidelines and education to improve care of infants with neonatal abstinence syndrome.

PURPOSE: : To develop and implement a program for the management of neonatal abstinence syndrome (NAS) and the use of the Finnegan Neonatal Abstinence Scoring Tool (FNAST). We evaluated knowledge gain in nurses as a result of implementation of the practice guidelines and education. SUBJECTS: : Participants included 68 nurses employed in a neonatal intensive care unit (NICU) at a single facility. DESIGN: : A nonexperimental, pretest/posttest study evaluated change in nursing knowledge about NAS and the use of the FNAST after implementation of evidence-based clinical practice guidelines and an educational project. METHODS: : Nurses were tested before and after participation in education about NAS. A subset of 10 nurses was evaluated using the FNAST with videos of infants having NAS. RESULTS: : Volunteer participation in the NAS educational project occurred in 81% of the NICU nurses. All nurses showed some improvement in scores on the posttest, with 2% to 44% improvement. All 10 nurses who participated in the interactive DVD test scored 90% or more against the FNAST criterion 1 week after participation in the educational project. CONCLUSION: : Evidence-based clinical practice guidelines and education around NAS and the FNAST equip caregivers with the necessary tools to consistently and accurately assess an infant with NAS when using the FNAST.

A Bivalent MAPS Vaccine Induces Protective Antibody Responses against Salmonella Typhi and Paratyphi A.

Infections by Salmonella Typhi and Paratyphi A strain are still a major cause of morbidity and mortality in developing countries. Generation of antibodies against the Vi capsular polysaccharide of S. Typhi via either pure polysaccharide or protein-polysaccharide conjugate is a very effective way to protect against S. Typhi. To date, there is no commercially available vaccine against S. Paratyphi A. The O-specific polysaccharide (OSP) has been generally considered a good vaccine target for Paratyphi A. Here, a bivalent vaccine against Vi and OSP was generated using the Multiple Antigen Presenting System (MAPS). Three different protein constructs, including CRM197, rEPA of Pseudomonas, and a pneumococcal fusion protein SP1500-SP0785, were fused to Rhizavidin (Rhavi) and evaluated their impact on immunogenicity when incorporated as fusion proteins affinity-bound to the two polysaccharides. We compared the antibody responses, antibody avidity, and cidal activity of sera post-immunization with monovalent vs. combination vaccines. We also wished to evaluate the generation of Vi-specific memory B cells in mice. We found little interference when combination vaccine was compared to monovalent vaccines with respect to antibody concentration and cidal activity of sera. Significant affinity maturation was noted for both Vi and OSP antigens. Thus, our preclinical results with a combination Vi- and OSP-MAPS vaccine strongly support the feasibility of this approach and its application of this approach to other important salmonella and Shigella species.

Simultaneous myocardial strain and dark-blood perfusion imaging using a displacement-encoded MRI pulse sequence.

The purpose of this study is to develop and evaluate a displacement-encoded pulse sequence for simultaneous perfusion and strain imaging. Displacement-encoded images in two to three myocardial slices were repeatedly acquired using a single-shot pulse sequence for 3 to 4 min, which covers a bolus infusion of Gadolinium contrast. The magnitudes of the images were T(1) weighted and provided quantitative measures of perfusion, while the phase maps yielded strain measurements. In an acute coronary occlusion swine protocol (n = 9), segmental perfusion measurements were validated against microsphere reference standard with a linear regression (slope 0.986, R(2) = 0.765, Bland-Altman standard deviation = 0.15 mL/min/g). In a group of ST-elevation myocardial infarction patients (n = 11), the scan success rate was 76%. Short-term contrast washout rate and perfusion are highly correlated (R(2) = 0.72), and the pixelwise relationship between circumferential strain and perfusion was better described with a sigmoidal Hill curve than linear functions. This study demonstrates the feasibility of measuring strain and perfusion from a single set of images.

Generation of protective pneumococcal-specific nasal resident memory CD4+ T cells via parenteral immunization.

The generation of tissue-resident memory T cells (TRM) is an essential aspect of immunity at mucosal surfaces, and it has been suggested that preferential generation of TRM is one of the principal advantages of mucosally administered vaccines. We have previously shown that antigen-specific, IL-17-producing CD4+ T cells can provide capsular antibody-independent protection against nasal carriage of Streptococcus pneumoniae; but whether pneumococcus-responsive TRM are localized within the nasal mucosa and are sufficient for protection from carriage has not been determined. Here, we show that intranasal administration of live or killed pneumococci to mice generates pneumococcus-responsive IL-17A-producing CD4+ mucosal TRM. Furthermore, we show that these cells are sufficient to mediate long-lived, neutrophil-dependent protection against subsequent pneumococcal nasal challenge. Unexpectedly, and in contrast with the prevailing paradigm, we found that parenteral administration of killed pneumococci also generates protective IL-17A+CD4+ TRM in the nasal mucosa. These results demonstrate a critical and sufficient role of TRM in prevention of pneumococcal colonization, and further that these cells can be generated by parenteral immunization. Our findings therefore have important implications regarding the generation of immune protection at mucosal surfaces by vaccination.

Novelty-facilitated extinction and the reinstatement of conditional human fear.

Although contemporary treatments for anxiety disorders are very efficient in reducing anxiety, return of fear after successful treatment is common which signifies a need for interventions that have a more enduring outcome. A recent laboratory study suggested that novelty-facilitated extinction, a simple modification of standard extinction which involves presenting a novel non-aversive stimulus during extinction, prevents spontaneous recovery, one laboratory analogue of return of fear. The current study assessed whether novelty-facilitated extinction can also prevent reinstatement, a second laboratory analogue of return of fear. Following differential fear conditioning, one group of participants underwent standard extinction training whereas the second was presented with a novel tone after the conditional stimulus that previously predicted the aversive unconditional stimulus (US). Three presentations of the USs alone reinstated differential electrodermal fear responses after standard extinction, but not after novelty-facilitated extinction. Moreover, replicating previous findings, the extent of return of fear was correlated with self-reported intolerance of uncertainty after standard extinction, but not after novelty-facilitated extinction. These results support the proposal that novelty-facilitated extinction training can reduce the extent of return of fear.

A cross-country comparative study on stress and quality of life in nursing students.

PURPOSE: This study was conducted to compare perceptions of stress and quality of life (QoL) among nursing students from three countries (the Philippines, Greece, and Nigeria) and to examine the impact of stress on their QoL. DESIGN AND METHODS: A comparative, cross-sectional research design was used in this study. Data were collected from 547 nursing students from three countries using the perceived stress scale (PSS) and the quality of life evaluation skill (QOLES). FINDINGS: Students' perceptions of stress and QoL were different across the three countries. Furthermore, higher stress perceptions were identified from taking care of patients, the clinical environment, and faculty, peer, and staff encounters, which predicted a negative QoL. PRACTICE IMPLICATIONS: The findings emphasized the need for empirically tested and culturally tailored interventions to effectively reduce stress and enhance the QoL in nursing students.

Latency and exposure-health associations in Gulf War veterans with early fatigue onsets: a case-control study.

PURPOSE: To see if self-reported exposures were associated with health in early-onset Gulf War illnesses (GWIs) cases and healthy Gulf War veteran controls. METHODS: Forty-nine cases and 44 controls completed questionnaires about wartime exposures and symptoms experienced. Odds ratios were calculated using 2 x 2 tables and logistic regression. The incubation curve of fatigue onsets in cases was drawn to highlight exposure/health associations using Sartwell's method and tested with the Shapiro-Wilk test. The incubation period was defined as the time from arrival in the Persian Gulf to fatigue onset. RESULTS: The incubation curve was right skewed and lognormally distributed (p = 0.48; p > 0.05 indicates lognormality), suggesting an association between a wartime exposure and fatigue. Exposure to oil fire smoke, pesticides, contaminated food or water, dead animals, scud missile attacks, dead bodies, prisoners of war, artillery or small arms fire, and chemical suits was significantly associated with GWIs. Pyridostigmine bromide (PB) was the only continuous exposure significantly associated with GWIs. The odds of having GWIs increased by 1.3% for every PB pill taken (95% confidence interval 1.001-1.02). There were significant trends toward worse health with greater intake of PB. CONCLUSIONS: These analyses suggest that wartime exposures, including exposure to PB, are associated with fatigue.

Prospective association between hypotension and idiopathic chronic fatigue.

OBJECTIVE: To determine whether there is an association between hypotension and incident cases of idiopathic chronic fatigue. DESIGN: A prospective study. SETTING: Johns Hopkins Precursors Study. PARTICIPANTS: Medical students (n = 876) in graduating classes from 1948 to 1964. MAIN OUTCOME MEASURE: 'Easy fatigability' reported by participants at 5- or 10-year follow-up after graduation. RESULTS: The unadjusted risk in women was 5.0 (95% exact confidence interval = 1.4 to 17.4) and in men was 1.7 (95% exact confidence interval = 0.8, to 3.5). CONCLUSION: These preliminary findings suggest that hypotension may be a risk factor for the development of idiopathic chronic fatigue in women.

Cerebral and systemic hemodynamics changes during upright tilt in chronic fatigue syndrome.

BACKGROUND AND PURPOSE: During head-up tilt (HUT), patients with chronic fatigue syndrome (CFS) have higher rates of neurally mediated hypotension (NMH) and postural tachycardia syndrome (POTS) than healthy controls. The authors studied whether patients with CFS were also more likely to have abnormal cerebral blood flow velocity (CBFV) compared with controls in response to orthostatic stress. METHODS: Transcranial Doppler monitoring of middle cerebral artery (MCA) CBFV was performed during 3-stage HUT prospectively in 26 patients with CFS and 23 healthy controls. At the same time, continuous monitoring of arterial blood pressure (BP), heart rate (HR), endtidal CO2 (ET-CO2) were performed. Results are reported as mean +/- SD. RESULTS: NMH developed in 21 patients with CFS and in 14 controls (P = .22). POTS was present in 9 CFS patients and 7 controls (P = .76). Supine HR was higher in CFS patients, but all other hemodynamics and CBFV measures were similar at baseline. The median time to hypotension did not differ, but the median time to onset of orthostatic symptoms was shorter in those with CFS (P < .001). The CBFV did not differ between groups in the supine posture, at 1 or 5 minutes after upright tilt, at 5 or 1 minute before the end of the test, or at termination of the test. Mean CBFV fell at termination of tilt testing in those with CFS and controls. ET-CO2 was lower at termination of the test in those with CFS versus controls (P = .002). CONCLUSIONS: The results of this study are not consistent with the hypothesis that patients with CFS have a distinctive pattern of MCA CBFV changes in response to orthostatic stress.

Familial aggregation of fainting in a case-control study of neurally mediated hypotension patients who present with unexplained chronic fatigue.

AIMS: We hypothesized that family history of fainting is a risk factor for adult-onset neurally mediated hypotension (NMH) in patients who present with chronic fatigue rather than fainting. METHODS AND RESULTS: A nested case-control study of Gulf War veterans gathered fainting histories directly from 197 first-degree relatives of 16 fatigued NMH cases, 26 fatigued controls, and 17 healthy controls. NMH status was determined by tilt testing. Female relatives of fatigued controls reported more fainting than female relatives of cases (P<0.01); there were no significant differences in the frequency of fainting in male relatives by case or control status, or in either gender by age at first faint or by familial relationship to the proband. The odds of NMH patients giving any family history of fainting were 0.56 (95% CI 0.15, 2.07). Recurrence risks calculated using lifetime prevalences of fainting in male military personnel of similar age to our participants were low (1.5-1.7) and did not differ by case or control status. CONCLUSION: Family history of fainting is not a risk factor for adult-onset NMH in fatigued veterans. Our findings may differ from other studies of familial aggregation in NMH because of study methods or because NMH-fatiguers may differ from NMH-fainters.