Biopsychosocial Correlates and Individual Differences for Eliciting Moral Elevation in Veterans With PTSD: An Experimental Case Series.

ABSTRACT: A promising approach to enhancing trauma-focused treatment is moral elevation-feeling inspired by witnessing a virtuous act. This study explored potential links between eliciting elevation and relevant outcomes in a series of case examples. Veterans with probable posttraumatic stress disorder completed experimental tasks including a written trauma narrative exercise and watching elevation-eliciting videos. Participants also completed baseline assessments, repeated measures of trauma-related cognitions, emotions, elevation, and saliva sample collection. Four cases were identified and reviewed: two positive responders (high elevation after videos) and two nonresponders (restricted elevation response). Positive responder cases reported decreased cognitions, emotions, and moral injury distress from after the trauma narrative to after elevation exercises, whereas nonresponders reported minimal to no changes. Positive responders also demonstrated decreases in cortisol, whereas nonresponders demonstrated increases in cortisol. Future work should examine whether elevation contributes to changes in biopsychosocial outcomes and identify individual factors that indicate who might benefit from elevation-based interventions.

Rehospitalization following Discharge from Newborn Nursery during Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic.

OBJECTIVE: This study aimed to compare rehospitalization rates, diagnoses, and well-baby nursery (WBN) length of stay (LOS) among rehospitalized infants born during the COVID-19 pandemic to those born prior. STUDY DESIGN: A retrospective comparison of 215 infants rehospitalized from March 1, 2019, to March 1, 2021, was performed in an urban academic center. Rates of readmission were determined for all infants using an unadjusted odds ratio. Among infants rehospitalized at ≤30 and ≤7 days, key cohort characteristics were analyzed using chi-square analysis, Fisher's exact test, independent t-test, and nonparametric testing as applicable. Differences in readmission diagnoses determined by International Classification of Diseases (ICD) code and chart review were evaluated with multivariable logistic regression comparing infants born during the pandemic to the year prior. RESULTS: Pandemic infants had a 51% increased odds of rehospitalization ≤7 days of discharge from WBN compared with prepandemic infants (95% confidence interval [CI]: 1.09-2.09). Rehospitalized infants born during the pandemic had shorter WBN LOS; infants rehospitalized ≤30 days had LOS of 54.3 ± 18.6 versus 59.6 ± 16.2 hours (p = 0.02) and infants rehospitalized ≤7 days had LOS of 53.8 ± 17.8 versus 60.8 ±17.0 hours (p = 0.02). The pandemic group of infants had a 3.5 increased odds of being readmitted for hyperbilirubinemia compared with other diagnoses after adjusting for biological sex, ethnicity, percent weight lost at time of discharge, gestational age, and mode of delivery (CI 1.9, 6.4). CONCLUSION: Rehospitalization ≤7 days post-WBN discharge was more common in infants born during the pandemic. Infants rehospitalized during the pandemic were more likely to have shorter WBN LOS and to be rehospitalized for hyperbilirubinemia. Retrospective analyses limit conclusions about causation but suggest that being born during the pandemic increased risk of rehospitalization for hyperbilirubinemia among infants in urban, under resourced setting warranting further investigation. KEY POINTS: · Newborns rehospitalized during the pandemic had a shorter newborn nursery stay.. · Newborns in the pandemic had a higher rate of rehospitalization within 7 days of birth compared to year prior.. · More infants who required readmission during the pandemic were hospitalized for hyperbilirubinemia..

Clinical, histopathologic, immunohistochemical, and electron microscopic findings in cutaneous monkeypox: A multicenter retrospective case series in Spain.

BACKGROUND: The worldwide outbreak of monkeypox has evidenced the usefulness of the dermatologic manifestations for its diagnosis. OBJECTIVE: To describe the histopathologic and immunohistochemical findings of monkeypox cutaneous lesions. METHODS: This is a retrospective histopathologic and immunohistochemical study of 20 patients with positive Monkeypox virus DNA polymerase chain reaction and immunohistochemical positivity for Vaccinia virus in cutaneous lesions. Four cases were also examined by electron microscopy. RESULTS: The most characteristic histopathologic findings consisted of full-thickness epidermal necrosis with hyperplasia and keratinocytic ballooning at the edges. In some cases, the outer root sheath of the hair follicle and the sebaceous gland epithelium were affected. Intraepithelial cytoplasmic inclusion bodies and scattered multinucleated keratinocytes were occasionally found. Immunohistochemically, strong positivity with anti-Vaccinia virus antibody was seen in the cytoplasm of ballooned keratinocytes. Electron microscopy study demonstrated numerous viral particles of monkeypox in affected keratinocytes. LIMITATIONS: Small sample size. Electron microscopic study was only performed in 4 cases. CONCLUSION: Epidermal necrosis and keratinocytic ballooning are the most constant histopathologic findings. Immunohistochemical positivity for Vaccinia virus was mostly detected in the cytoplasm of the ballooned keratinocytes. These findings support the usefulness of histopathologic and immunohistochemical studies of cutaneous lesions for diagnosis of monkeypox.

Association of periodontitis with cognitive decline and its progression: Contribution of blood-based biomarkers of Alzheimer's disease to this relationship.

AIM: To assess whether periodontitis is associated with cognitive decline and its progression as well as with certain blood-based markers of Alzheimer's disease. MATERIALS AND METHODS: Data from a 2-year follow-up prospective cohort study (n = 101) was analysed. Participants with a previous history of hypertension and aged ≥60 years were included in the analysis. All of them received a full-mouth periodontal examination and cognitive function assessments (Addenbrooke's Cognitive Examination (ACE) and Mini-Mental State Examination [MMSE]). Plasma levels of amyloid beta (Aß)1-40 , Aß1-42 , phosphorylated and total Tau (p-Tau and t-Tau) were determined at baseline, 12 and 24 months. RESULTS: Periodontitis was associated with poor cognitive performance (MMSE: ß = -1.5 [0.6]) and progression of cognitive impairment (hazard ratio [HR] = 1.8; 95% confidence interval: 1.0-3.1). Subjects with periodontitis showed greater baseline levels of p-Tau (1.6 [0.7] vs. 1.2 [0.2] pg/mL, p < .001) and Aß1-40 (242.1 [77.3] vs. 208.2 [73.8] pg/mL, p = .036) compared with those without periodontitis. Concentrations of the latter protein also increased over time only in the periodontitis group (p = .005). CONCLUSIONS: Periodontitis is associated with cognitive decline and its progression in elderly patients with a previous history of hypertension. Overexpression of p-Tau and Aß1-40 may play a role in this association.

Alzheimer's Disease Seen through the Eye: Ocular Alterations and Neurodegeneration.

Alzheimer's Disease (AD) is one of the main neurodegenerative diseases worldwide. Unfortunately, AD shares many similarities with other dementias at early stages, which impedes an accurate premortem diagnosis. Therefore, it is urgent to find biomarkers to allow for early diagnosis of the disease. There is increasing scientific evidence highlighting the similarities between the eye and other structures of the CNS, suggesting that knowledge acquired in eye research could be useful for research and diagnosis of AD. For example, the retina and optic nerve are considered part of the central nervous system, and their damage can result in retrograde and anterograde axon degeneration, as well as abnormal protein aggregation. In the anterior eye segment, the aqueous humor and tear film may be comparable to the cerebrospinal fluid. Both fluids are enriched with molecules that can be potential neurodegenerative biomarkers. Indeed, the pathophysiology of AD, characterized by cerebral deposits of amyloid-beta (Aß) and tau protein, is also present in the eyes of AD patients, besides numerous structural and functional changes observed in the structure of the eyes. Therefore, all this evidence suggests that ocular changes have the potential to be used as either predictive values for AD assessment or as diagnostic tools.

Ceramide/Sphingosine 1-Phosphate Axis as a Key Target for Diagnosis and Treatment in Alzheimer's Disease and Other Neurodegenerative Diseases.

Alzheimer's disease (AD) is considered the most prevalent neurodegenerative disease and the leading cause of dementia worldwide. Sphingolipids, such as ceramide or sphingosine 1-phosphate, are bioactive molecules implicated in structural and signaling functions. Metabolic dysfunction in the highly conserved pathways to produce sphingolipids may lead to or be a consequence of an underlying disease. Recent studies on transcriptomics and sphingolipidomics have observed alterations in sphingolipid metabolism of both enzymes and metabolites involved in their synthesis in several neurodegenerative diseases, including AD. In this review, we highlight the most relevant findings related to ceramide and neurodegeneration, with a special focus on AD.

Examining the Link Between Intolerance of Uncertainty and Positive and Negative Urgency in Veterans With Comorbid Posttraumatic Stress Disorder and Substance Use Disorders.

Posttraumatic stress disorder (PTSD) and substance use disorders (SUD) are highly comorbid among the veteran population. Impulsivity, particularly negative and positive urgency, are prevalent within this dual-diagnosis population and associated with negative outcomes. One possible correlate of negative/positive urgency is intolerance of uncertainty (IU). IU is associated with exacerbated PTSD symptom severity and increased risk for substance use. However, few studies have examined the link between IU and negative/positive urgency in dual-diagnosis populations. This study aimed to examine whether there was a significant association between trait IU and baseline negative and positive urgency in veterans seeking treatment for both PTSD and SUD. In a sample of 114 veterans from a 6-week residential treatment program, IU was significantly associated with higher negative and positive urgency. Further research is warranted to extend these findings and examine whether IU plays an important role in negative/positive urgency for dual-diagnosis populations.

Periodontitis and systemic markers of neurodegeneration: A case-control study.

AIM: To investigate whether periodontitis is associated with amyloid beta (Aß) peptides and whether systemic inflammation could act as a potential mediator of this link. MATERIALS AND METHODS: A case-control study was designed including 75 patients with periodontitis (cases) and 75 age-balanced and gender-matched participants without periodontitis (controls). Full-mouth periodontal evaluation was performed in all participants. Demographic, clinical and behaviour data were also recorded. Fasting blood samples were collected, and serum levels of interleukin 6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), Aß1-40 and Aß1-42 were determined. RESULTS: Cases showed higher levels of IL-6 (8.7 ± 3.2 vs. 4.8 ± 0.5 pg/ml), hs-CRP (3.3 ± 1.2 vs. 0.9 ± 0.7 mg/L), Aß1-40 (37.3 ± 6.0 vs. 30.3 ± 1.8 pg/ml) and Aß1-42 (54.5 ± 10.6 vs. 36.5 ± 10.0 pg/ml) when compared to controls (all p < .001). Diagnosis of periodontitis was statistically significantly associated with circulating Aß1-40 ( ßcoefficientadjusted  = 6.9, 95% CI: 5.4-8.3; p < .001) and Aß1-42 ( ßcoefficientadjusted  = 17.8, 95% CI: 14.4-21.3; p < .001). Mediation analysis confirmed hs-CRP and IL-6 as mediators of this association. CONCLUSIONS: Periodontitis is associated with increased peripheral levels of Aß. This finding could be explained by enhanced systemic inflammation that can be seen in patients with periodontitis.

Cortisol as a Biomarker of Alcohol Use in Combat Veterans: A Literature Review and Framework for Future Research.

Objective: Alcohol use and alcohol use disorders (AUDs) are an increasing concern among veterans, particularly those from recent conflicts in Iraq and Afghanistan. The study of biomarkers in alcohol use and AUD has moved to enhancing the understanding of the development and maintenance of AUDs, as well as investigating its association with clinical severity and potential predictors of treatment response. Cortisol, a glucocorticoid known as a stress hormone, has been linked with both stress and trauma, as well as increased alcohol suppression effects. Method/Results: The present review summarizes existing literature and presents suggestions for future research to evaluate whether cortisol may be a possible biomarker of alcohol use disorder risk in combat veterans. Specifically, aspects of combat deployments and high levels of PTSD, coupled with the stress of reintegration may dysregulate cortisol and increase risk to AUD. There may also be bidirectional impacts, such that alcohol is used as a coping mechanism and can dysregulate hypothalamic pituitary adrenal (HPA) axis functioning and cortisol. Conclusions: In the context of this framework, cortisol may serve as a biomarker for the development of AUD, as well as a biomarker of risk or relapse. This review ends with both theoretical and clinical implications, as well as directions for future research.

Mitochondrial Dysfunction and Calcium Dysregulation in Leigh Syndrome Induced Pluripotent Stem Cell Derived Neurons.

Leigh syndrome (LS) is the most frequent infantile mitochondrial disorder (MD) and is characterized by neurodegeneration and astrogliosis in the basal ganglia or the brain stem. At present, there is no cure or treatment for this disease, partly due to scarcity of LS models. Current models generally fail to recapitulate important traits of the disease. Therefore, there is an urgent need to develop new human in vitro models. Establishment of induced pluripotent stem cells (iPSCs) followed by differentiation into neurons is a powerful tool to obtain an in vitro model for LS. Here, we describe the generation and characterization of iPSCs, neural stem cells (NSCs) and iPSC-derived neurons harboring the mtDNA mutation m.13513G>A in heteroplasmy. We have performed mitochondrial characterization, analysis of electrophysiological properties and calcium imaging of LS neurons. Here, we show a clearly compromised oxidative phosphorylation (OXPHOS) function in LS patient neurons. This is also the first report of electrophysiological studies performed on iPSC-derived neurons harboring an mtDNA mutation, which revealed that, in spite of having identical electrical properties, diseased neurons manifested mitochondrial dysfunction together with a diminished calcium buffering capacity. This could lead to an overload of cytoplasmic calcium concentration and the consequent cell death observed in patients. Importantly, our results highlight the importance of calcium homeostasis in LS pathology.

Interventions to improve working conditions of nursing staff in acute care hospitals: Scoping review.

AIM: To conduct a scoping review to examine and map the interventions proposed for the improvement of the working conditions of nursing staff in acute care hospitals. BACKGROUND: The Registered Nurse Forecasting (RN4CAST) project and other studies have determined the impact that the nursing staff has on the quality of care. The nursing staff's higher levels of burnout, job dissatisfaction and negative perception of the quality of care provided caused worse health outcomes. METHODS: A scoping review was carried out. By searching in SCOPUS, PubMed, CINAHL, Cochrane, Dialnet and in the grey literature, 705 potentially relevant papers were identified. The final analysis included 21 papers and three grey documents. RESULTS: The studies analysed proposed interventions at the macro-management, meso-management and micro-management levels, although the interventions at the macro- and meso-levels produce better staff outcomes. CONCLUSIONS: The findings of this review can be applied to management at different levels: measures to improve the patient-nurse ratio at the macro-management level, the horizontal hierarchies at the meso-management level, the mind-body techniques at the micro-management level. IMPLICATIONS FOR NURSING MANAGEMENT: Nurse managers and leaders should implement interventions at different organisational levels to improve the working conditions of the nursing staff and other health outcomes.

Specific variants in WDR35 cause a distinctive form of Ellis-van Creveld syndrome by disrupting the recruitment of the EvC complex and SMO into the cilium.

Most patients with Ellis-van Creveld syndrome (EvC) are identified with pathogenic changes in EVC or EVC2, however further genetic heterogeneity has been suggested. In this report we describe pathogenic splicing variants in WDR35, encoding retrograde intraflagellar transport protein 121 (IFT121), in three families with a clinical diagnosis of EvC but having a distinctive phenotype. To understand why WDR35 variants result in EvC, we analysed EVC, EVC2 and Smoothened (SMO) in IFT-A deficient cells. We found that the three proteins failed to localize to Wdr35(-/-) cilia, but not to the cilium of the IFT retrograde motor mutant Dync2h1(-/-), indicating that IFT121 is specifically required for their entry into the ciliary compartment. Furthermore expression of Wdr35 disease cDNAs in Wdr35(-/-) fibroblasts revealed that the newly identified variants lead to Hedgehog signalling defects resembling those of Evc(-/-) and Evc2(-/-) mutants. Together our data indicate that splicing variants in WDR35, and possibly in other IFT-A components, underlie a number of EvC cases by disrupting targeting of both the EvC complex and SMO to cilia.

Identification and functional validation of rare coding variants in genes linked to monogenic obesity.

OBJECTIVE: Rare cases of monogenic obesity, which may respond to specific therapeutics, can remain undetected in populations in which polygenic obesity is prevalent. This study examined rare DNA variation in established monogenic obesity genes within a community using whole-exome sequence data from 6803 longitudinally studied individuals. METHODS: Exome data across 15 monogenic obesity genes were analyzed for nonsynonymous variants observed in any child with a maximum BMI z score > 2 (N = 279) but not observed in a child with a maximum BMI z score ≤ 0 (n = 1542) or that occurred in adults in the top 5th percentile of BMI (n = 263) but not in adults below the median BMI (n = 2629). Variants were then functionally analyzed using luciferase assays. RESULTS: The comparisons between cases of obesity and controls identified eight missense variants in six genes: DYRK1B, KSR2, MC4R, NTRK2, PCSK1, and SIM1. Among these, MC4R p.A303P and p.R165G were previously shown to impair MC4R function. Functional analyses of the remaining six variants suggest that KSR2 p.I402F and p.T193I and NTRK2 p.S249Y alter protein function. CONCLUSIONS: In addition to MC4R, rare missense variants in KSR2 and NTRK2 may potentially explain the severe obesity observed for the carriers.

Starting early: Case study of mentoring for undergraduate training through the Veterans Health Administration and implications for promoting equity.

Undergraduate mentoring and research internships promote entry into graduate training, academic success, research productivity, and greater career satisfaction. Most pathway programs to enhance representation within academia and health care intervene at the graduate level, leaving a critical gap in undergraduate training. The Veterans Health Administration's (VHA's) national network of clinicians and researchers is uniquely suited to provide equitable access to quality mentorship and education for undergraduates interested in health care careers. We present a program evaluation case study of a VHA undergraduate training program incorporating empirically supported components that promote success and transition to graduate school, including tiered mentorship, a didactic-preceptor model, hands-on experience, and interdisciplinary work. We describe participant characteristics and consider the program elements that may contribute to trainees' success, highlighting the importance of undergraduate training within a health care system like VHA. We found that all program completers attained their bachelor's degree and nearly 70% advanced to graduate studies. Despite some differences based on participant characteristics, all program components were deemed useful preparation for professional success, with hands-on research experience and mentoring cited as the most helpful. The promising results of our case study demonstrate the feasibility of successfully implementing an undergraduate training program to provide a pathway to advanced careers in health care within the VHA. We posit that programs like ours can serve as a framework for creating pathway training programs that target undergraduates traditionally underrepresented, subsequently empowering them to pursue health care careers, and ultimately increasing diversity by training professionals who are better prepared to assist with diverse patient needs. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Real life experience of tafamidis for the treatment of Spanish patients with Val30Met transthyretin amyloidosis with polyneuropathy.

INTRODUCTION: Tafamidis is the only approved transthyretin stabiliser approved for the treatment of variant transthyretin amyloidosis (A-ATTRv) related polyneuropathy (PNP). The aim of this study is to analyse the effectiveness of tafamidis in a real-world setting in Spain. METHODS: This is a national multicenter study in which patients with V30M A-ATTR related PN treated with tafamidis for at least 1 year were included. Clinical, demographic, analytical and neurophysiological variables were analysed. RESULTS: 100 patients were recruited. Overall, 47 patients (47%) were classified as complete responders, 32 (32%) as partial responders and 21 (21%) as non-responders. The median duration of treatment with tafamidis was 35 months. Better treatment response was shown in patients with in polyneuropathy disability score (PND) I, lower neuropathy impairment score (NIS), compound muscle action potential (CMAP) and Norfolk QoL questionnaire. Higher albumin levels and lower NTproBNP levels were also associated with better treatment response. A basal NIS≥15 predicts that the patient could be a non-responder with a 60% probability. CONCLUSIONS: Our results reinforce the tafamidis efficacy to treat A-ATTRv-PNP if started early in the disease course. Patients with the V30M variant, NIS<15 and PND I are the most appropriate subjects for this treatment.

Glycemic Measures in Childhood as Predictors of Future Diabetes-Related Microvascular Complications in an Indigenous American Population.

OBJECTIVE: To examine the role of glycemic measures performed during childhood in predicting future diabetes-related nephropathy and retinopathy in a high-risk indigenous American cohort. RESEARCH DESIGN AND METHODS: We studied associations between glycated hemoglobin (HbA1c) and 2-h plasma glucose (PG), measured during childhood (age 5 to <20 years) in a longitudinal observational study of diabetes and its complications (1965-2007), and future albuminuria (albumin creatinine ratio [ACR] ≥30 mg/g), severe albuminuria (ACR ≥300 mg/g), and retinopathy (at least one microaneurysm or hemorrhage or proliferative retinopathy on direct ophthalmoscopy). Areas under the receiver operating characteristic curve (AUCs) for childhood glycemic measures when predicting nephropathy and retinopathy were compared. RESULTS: Higher baseline levels of HbA1c and 2-h PG significantly increased the risk of future severe albuminuria (HbA1c: hazard ratio [HR] 1.45 per %; 95% CI 1.02-2.05 and 2-h PG: HR 1.21 per mmol/L; 95% CI 1.16-1.27). When categorized by baseline HbA1c, children with prediabetes had a higher incidence of albuminuria (29.7 cases per 1,000 person-years [PY]), severe albuminuria (3.8 cases per 1,000 PY), and retinopathy (7.1 cases per 1,000 PY) than children with normal HbA1c levels (23.8, 2.4, and 1.7 cases per 1,000 PY, respectively); children with diabetes at baseline had the highest incidence of the three complications. No significant differences were observed between AUCs for models with HbA1c, 2-h PG, and fasting PG when predicting albuminuria, severe albuminuria, or retinopathy. CONCLUSIONS: In this study, higher glycemia levels ascertained by HbA1c and 2-h PG during childhood were associated with future microvascular complications; this demonstrates the potential utility of screening tests performed in high-risk children in predicting long-term health outcomes.

Feasibility and acceptability of comprehensive virtual treatment in eating disorders: perspectives from patients, parents and therapists during the COVID-19 pandemic.

BACKGROUND: Lockdowns and social distancing as a result of the COVID-19 pandemic have brought about the need to continue treatment virtually in patients with Eating Disorders (ED). OBJECTIVE: To evaluate feasibility, acceptability and adherence to virtual treatment in patients, families and therapists. METHODS: Fourteen patients, 10 family members and eight therapists from an intensive outpatient program for ED answered online surveys and a SWOT analysis was performed with the responses. RESULTS: Virtual treatment during lockdown was considered feasible and useful by all respondents. Fear of contagion and the presence of parents in the home were identified as strengths. Parents reported problems with nutritional plan compliance, especially in anorexia patients. Therapists highlighted the importance of methodological adaptations in sessions to improve participation. Adherence to sessions was 100% for family members and 90% for patients. CONCLUSIONS: Adaptation to a virtual program is a valid and useful option during lockdowns. It improves family participation, but does not replace face-to-face treatment.

Toxic metals from atmospheric particulate matter in food species of tomato (Solanum lycopersicum) and strawberry (Fragaria x ananassa) used in urban gardening. A closed chamber study.

In this work, two plant foods, strawberry and tomato, were subjected to exposure to metals from synthetic airborne particles in a closed chamber experiment. The synthetic particles were obtained in the laboratory. Within the closed chamber, particles were added and recirculated for 4 days in a turbulent air stream, causing deposition on the different parts of the plants. They were evaluated because of their increasingly frequent cultivation in urban gardens of cities. The main objectives were to determine whether the species accumulate metals significantly, which species accumulate the most, and in which parts of the plant. Finally, an attempt was made to differentiate the accumulation of pollutants by surface deposition on leaves and fruits from the adsorbed metals into the leaf or the fruit by their stomata or cuticles. The concentration of heavy metals was quantified in fruits, leaves and the soil after exposure. Metals were evaluated as a whole and individually, both in dry and fresh weight basis. The decrease of particulate matter and metals in the air inside the chamber was also studied in order to evaluate the use of both food species as air purifier by vertical gardens. The concentration of metals in plants (mg kg-1) and airborne particles (mg m-3) was measured by microwave plasma optical emission spectroscopy (MP-AES). For the sake comparison of total amount of metals in the samples concentrations were normalized. Strawberries was the food species that accumulated the largest amount of metals. In a dry weight basis, tomato leaves and strawberry fruits were the parts of the plants with higher accumulation capacity of particles and metals. The potential toxic elements Cd, Ni and Cr in tomato leaves and in strawberry fruits had a higher presence in the interior of the plant system. In a fresh weight basis, the strawberry fruit had the most accumulation capacity for metals.