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Traumatic brain injury (TBI) is a ubiquitous, common sequela of accidents with an annual prevalence of several million cases worldwide. In forensic pathology, structural proteins of the cellular compartments of the CNS in serum and cerebrospinal fluid (CSF) have been predominantly used so far as markers of an acute trauma reaction for the biochemical assessment of neuropathological changes after TBI. The analysis of endogenous metabolites offers an innovative approach that has not yet been considered widely in the assessment of causes and circumstances of death, for example after TBI. The present study, therefore, addresses the question whether the detection of metabolites by liquid-chromatography-mass spectrometry (LC/MS) analysis in post mortem CSF is suitable to identify TBI and to distinguish it from acute cardiovascular control fatalities (CVF). Metabolite analysis of 60 CSF samples collected during autopsies was performed using high resolution (HR)-LC/MS. Subsequent statistical and graphical evaluation as well as the calculation of a TBI/CVF quotient yielded promising results: numerous metabolites were identified that showed significant concentration differences in the post mortem CSF for lethal acute TBI (survival times up to 90 min) compared to CVF. For the first time, this forensic study provides an evaluation of a new generation of biomarkers for diagnosing TBI in the differentiation to other causes of death, here CVF, as surrogate markers for the post mortem assessment of complex neuropathological processes in the CNS (“neuroforensomics”). [ABSTRACT FROM AUTHOR]

The global spread of multidrug-resistant Escherichia coli threatens human, animal, and environmental health. Despite the recognition of water bodies as potential reservoirs, research on antimicrobial resistance (AMR) and antibiotic residues in the Baltic Sea is limited. In this study, we examined the presence of ESBL-producing E. coli in surface water in northeastern Germany. We then conducted phenotypic and genotypic analyses of the strains, which encompassed AMR and heavy metal/metalloid tolerance, biofilm formation, and detailed plasmid examination. In addition, we used solid-phase extraction with ultra-high performance liquid chromatography and mass spectrometry to quantify antibiotic residues. Our analysis identified 30 ESBL-producing E. coli isolates, some of which were associated with clinically relevant high-risk clonal lineages. We detected antibiotic residues in the environmental samples, but the antibiotic concentrations were significantly lower compared to wastewater samples. These results suggest that the Baltic Sea surface water could serve as a reservoir for ESBL-producing E. coli and clinically relevant antibiotics. [ABSTRACT FROM AUTHOR]

Background: Prior studies suggest cost-sharing decreases buprenorphine dispensing. However, these studies used databases that only report prescriptions filled by patients, not those that were "abandoned." Consequently, the studies could not calculate the probability of buprenorphine prescription abandonment or evaluate whether cost-sharing is associated with abandonment. Objective: To evaluate the association between cost-sharing and buprenorphine prescription abandonment. Design: Cross-sectional analysis of the IQVIA Formulary Impact Analyzer, a pharmacy transaction database representing 63% of U.S. retail pharmacies. The database includes transaction records ("claims") for prescriptions even if they are not filled. Participants: Buprenorphine claims in 2022 among commercially insured and Medicare patients. Main Measures: We evaluated the association between cost-sharing per 30-day supply and abandonment using logistic regression, controlling for patient characteristics, product type, and buprenorphine use in the prior 180 days. We assessed for effect modification by prior buprenorphine use. Key Results: Analyses included 2,346,994 and 1,242,596 buprenorphine prescription claims for commercially insured and Medicare patients, respectively. Among these claims, mean (SD) cost-sharing per 30-day supply was $28.1 (46.4) and $8.4 (20.2), and 1.5% and 1.2% were abandoned. Each $10 increase in cost-sharing per 30-day supply was associated with a 0.09 (95% CI: 0.09, 0.10) and 0.09 (95% CI: 0.08, 0.10) percentage-point increase in abandonment among commercially insured and Medicare patients. Among commercially insured and Medicare patients without prior buprenorphine use, respectively, a $10 increase in cost-sharing per 30-day supply was associated with a 0.12 (95% CI: 0.11, 0.14) and 0.13 (95% CI: 0.07, 0.18) percentage-point higher increase in the probability of abandonment compared with patients with > 90 days of prior buprenorphine use. Conclusions: Among commercially insured and Medicare patients, buprenorphine prescription abandonment is rare and only minimally associated with cost-sharing. Findings suggest elimination of buprenorphine cost-sharing should only be one component of a larger, multi-faceted campaign to increase buprenorphine dispensing. [ABSTRACT FROM AUTHOR]

Sepsis is one of the major threats for the survival and prognosis of patients in intensive care units. In cases where detailed clinical data and monitoring is available, the diagnosis of sepsis is reliable. But when clinical data are incomplete or missing and sepsis is only suspected based on the autopsy results, the picture is often equivocal. This report describes the gross pathological findings obtained from the autopsy of a 48-year-old woman with Crohn's disease after surgical intervention. Macroscopically, we found intestinal perforation and signs of peritonitis. Histologically, the pulmonary/bronchial arteries were lined with E-selectin (CD 62E)-positive endothelial cells, which are an established postmortem histological marker of sepsis. We extended our investigations to the cerebral cortex and subcortical medullary layer. The endothelium of the cortical vessels and those in the cerebral medullary layer were likewise immunopositive for E-selectin. Furthermore, numerous TMEM119-positive, highly ramified microglial cell profiles were found in the grey and white matter. Microglial cells were lining the vascular profiles. In addition, TMEM119-positive microglial profiles were abundant in the cerebrospinal fluid (CSF). Multiorgan E-selectin positivity of the vascular endothelia provides further evidence for the postmortem diagnosis of sepsis. [ABSTRACT FROM AUTHOR]

Background: Prior research demonstrates that SARS-COV-2 infection can be associated with a broad range of mental health outcomes including depression symptoms. Veterans, in particular, may be at elevated risk of increased depression following SARS-COV-2 infection given their high rates of pre-existing mental and physical health comorbidities. However, few studies have tried to isolate SARS-COV-2 infection associations with long term, patient-reported depression symptoms from other factors (e.g., physical health comorbidities, pandemic-related stress). Objective: To evaluate the association between SARS-COV-2 infection and subsequent depression symptoms among United States Military Veterans. Design: Survey-based non-randomized cohort study with matched comparators. Participants: A matched-dyadic sample from a larger, stratified random sample of participants with and without known to SARS-COV-2 infection were invited to participate in a survey evaluating mental health and wellness 18-months after their index infection date. Sampled participants were stratified by infection severity of the participant infected with SARS-COV-2 (hospitalized or not) and by month of index date. A total of 186 participants in each group agreed to participate in the survey and had sufficient data for inclusion in analyses. Those in the uninfected group who were later infected were excluded from analyses. Main Measures: Participants were administered the Patient Health Questionnaire-9 as part of a phone interview survey. Demographics, physical and mental health comorbidities were extracted from VHA administrative data. Key Results: Veterans infected with SARS-COV-2 had significantly higher depression symptoms scores compared with those uninfected. In particular, psychological symptoms (e.g., low mood, suicidal ideation) scores were elevated relative to the comparator group (MInfected = 3.16, 95%CI: 2.5, 3.8; MUninfected = 1.96, 95%CI: 1.4, 2.5). Findings were similar regardless of history of depression. Conclusion: SARS-COV-2 infection was associated with more depression symptoms among Veterans at 18-months post-infection. Routine evaluation of depression symptoms over time following SARS-COV-2 infection is important to facilitate adequate assessment and treatment. [ABSTRACT FROM AUTHOR]

Purpose: The Oldenburg Sentence Test (OLSA) is a German matrix test designed to determine speech recognition thresholds (SRT). It is widely used for hearing-aids and cochlear implant fitting, but an age-adjusted standard is still lacking. In addition, knowing that the ability to concentrate is an important factor in OLSA performance, we hypothesized that OLSA performance would depend on the time of day it was administered. The aim of this study was to propose an age standardization for the OLSA and to determine its diurnal performance. Methods: The Gutenberg Health Study is an ongoing population-based study and designed as a single-centre observational, prospective cohort study. Participants were interviewed about common otologic symptoms and tested with pure-tone audiometry and OLSA. Two groups—subjects with and without hearing loss—were established. The OLSA was performed in two runs. The SRT was evaluated for each participant. Results were characterized by age in 5-year cohorts, gender and speech recognition threshold (SRT). A time stamp with an hourly interval was also implemented. Results: The mean OLSA SRT was − 6.9 ± 1.0 dB (group 1 male) and − 7.1 ± 0.8 dB (group 1 female) showing an inverse relationship with age in the whole cohort, whereas a linear increase was observed in those without hearing loss. OLSA-SRT values increased more in males than in females with increasing age. No statistical significance was found for the diurnal performance. Conclusions: A study with 2900 evaluable Oldenburg Sentence Tests is a novelty and representative for the population of Mainz and its surroundings. We postulate an age- and gender-standardized scale for the evaluation of the OLSA. In fact, with an intergroup standard deviation (of about 1.5 dB) compared to the age dependence of 0.7 dB/10 years, this age normalization should be considered as clinically relevant. [ABSTRACT FROM AUTHOR]

Copyright of Rechtsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Acute pulmonary embolism (PE) is a potentially life-threatening disease. Current guidelines suggest risk-adapted management. Hospitalization is required for intermediate- and high-risk patients. Early discharge and home treatment are considered safe in the majority of low-risk patients. In this study, we describe characteristics, discharge, and outcome of outpatients diagnosed with acute PE at a tertiary care center. All outpatients undergoing computed tomography pulmonary angiography or ventilation/perfusion lung scan between 01.01.2016 and 31.12.2019 at the University Hospital Vienna, Austria, were screened for a PE diagnosis. Electronic patient charts were used to extract characteristics, clinical course, and outcomes. Within the 4-year period, 709 outpatients (median age: 62 years, 50% women) were diagnosed with PE. Thirty-three (5%) patients were classified as high-risk, 159 (22%) as intermediate-high, 332 (47%) as intermediate-low, and 185 (26%) as low-risk PE according to the European Society of Cardiology risk stratification. In total, 156 (22%) patients (47% with low-risk and 20% with intermediate-low-risk PE) were discharged as outpatients and received home treatment. Rates for home treatment increased 2.4-fold during the study period. Thirty-day mortality in the entire population was 4.9%. All low-risk patients and all but one patient with home treatment survived the first 30 days. Home treatment significantly increased over time and seems to be safe in routine clinical practice. Notably, one in five intermediate-low-risk patients was discharged immediately, suggesting that a subpopulation of intermediate-low-risk patients may also be eligible for home treatment. [ABSTRACT FROM AUTHOR]

To determine the occurrence and distribution of prevalent viruses in commercially important vineyards, a survey was carried out in all thirteen wine-growing regions in Germany. Results reveal that the recently emerged Grapevine pinot gris virus (GPGV) was the most abundant virus with a percentage of 18% prevalence, followed by 13% Grapevine fleck virus (GFkV), 9% Grapevine leafroll-associated virus 1 (GLRaV-1), 4% Grapevine fanleaf virus (GFLV), 2% Raspberry ringspot virus (RpRSV), 2% Arabis mosaic virus (ArMV) and 2% Grapevine leafroll-associated virus 3 (GLRaV-3). Distribution of some viruses varies greatly between individual regions, thus regional hotspots or gradients were detected. GPGV for example is mostly found in southeastern Germany, while its incidence decreases to the north along the river Rhine. The findings of this survey provide an overview of the allocation of the most prevalent grapevine viruses in Germany and can support regional virus management and national risk assessment especially GPGV. [ABSTRACT FROM AUTHOR]

Copyright of Rechtsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Rechtsmedizin is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Sleep is an important factor in well-being, especially during the transition to college when academic and social commitments increase. Identifying factors that contribute to poor sleep (including short duration and increased variability in duration) can support development of interventions. Affect and emotion reactivity are factors that could contribute to sleep, and have not been studied in relation to sleep variables among first-year college students during their adjustment to the college environment. This adjustment might be difficult for some students, and therefore elicit affect fluctuations that contribute to poor sleep. Alternatively, sleep could contribute to daily affect. The present daily diary study examined bidirectional relations between daily sleep and affect, as well as between emotion reactivity and sleep (duration and variability) and affect (daily and overall variability) in first-year college students. Method: First-year college students (n = 244; 86.1% female) completed a baseline survey including measures of emotion reactivity and anxiety and depressive symptoms, followed by 7 days of a once-per-day diary, reporting on their affect and sleep duration. Results: On days when individuals reported increased sleep duration, they also tended to experience greater positive affect the following day (p =.01). Those who experienced high levels of emotion reactivity also experienced more negative affect (p <.001) and negative affect variability (p <.001). Conclusion: Emotion reactivity might identify college students who experience more negative affect and are possibly at risk to develop mental health disorders. The importance of sleep health should continue to be emphasized to students as they transition to college. [ABSTRACT FROM AUTHOR]

Routine coronal paraffin-sections through the dorsal frontal and parieto-occipital cortex of a total of sixty cases with divergent causes of death were immunohistochemically (IHC) stained with an antibody against TMEM119. Samples of cerebrospinal fluid (CSF) of the same cases were collected by suboccipital needle-puncture, subjected to centrifugation and processed as cytospin preparations stained with TMEM119. Both, cytospin preparations and sections were subjected to computer-assisted density measurements. The density of microglial TMEM119-positive cortical profiles correlated with that of cytospin results and with the density of TMEM119-positive microglial profiles in the medullary layer. There was no statistically significant correlation between the density of medullary TMEM119-positive profiles and the cytospin data. Cortical microglial cells were primarily encountered in supragranular layers I, II, and IIIa and in infragranular layers V and VI, the region of U-fibers and in circumscribed foci or spread in a diffuse manner and high density over the white matter. We have evidence that cortical microglia directly migrate into CSF without using the glympathic pathway. Microglia in the medullary layer shows a strong affinity to the adventitia of deep vessels in the myelin layer. Selected rapidly fatal cases including myocardial infarcts and drowning let us conclude that microglia in cortex and myelin layer can react rapidly and its reaction and migration is subject to pre-existing external and internal factors. Cytospin preparations proved to be a simple tool to analyze and assess complex changes in the CNS after rapid fatal damage. There is no statistically significant correlation between cytospin and postmortem interval. Therefore, the quantitative analyses of postmortem cytospins obviously reflect the neuropathology of the complete central nervous system. Cytospins provide forensic pathologists a rather simple and easy to perform method for the global assessment of CNS affliction. [ABSTRACT FROM AUTHOR]

Purpose: The aim of the study was to develop the German Hearing in Noise Test (HINT) with female speaker by fulfilling the recommendations by International Collegium of Rehabilitative Audiology (ICRA) for using a female speaker to create new multilingual speech tests and to determine norms and to compare these norms with German male speech tests—the male speakers HINT and the Oldenburg Sentence Test (OLSA). Methods: The HINT with a female speaker consists of the same speech material as the male speaking HINT. After recording the speech material, 10 normal hearing subjects were included to determine the performance–intensity function (PI function). 24 subjects were part of the measurements to determine the norms and compare them with the norms of male HINT and OLSA. Comparably, adaptive, open-set methods under headphones (HINT) and sound field (OLSA) were used. Results: Acoustic phonetic analysis demonstrated significant difference in mean fundamental frequency, its range and mean speaking rate between both HINT speakers. The calculated norms by three of the tested four conditions of the HINT with a female speaker are not significantly different from the norms with a male speaker. No significant effect of the speaker's gender of the first HINT measurement and no significant correlation between the threshold results of the HINT and the OLSA were determined. Conclusions: The Norms for German HINT with a female speaker are comparable to the norms of the HINT with a male speaker. The speech intelligibility score of the HINT does not depend on the speakers' gender despite significant difference of acoustic–phonetic parameters between the female and male HINT speaker's voice. Instead, the speech intelligibility rating must be seen as a function of the used speech material. [ABSTRACT FROM AUTHOR]

Intramuscular hemorrhages at autopsy can have a variety of traumatic as well as non-traumatic causes, but their recognition in electrical deaths is almost a rarity. We report on two autopsy cases of electrical fatalities, the first relating to a portion of the right upper human extremity, consisting (only) of the forearm and hand, while the other case relates to a female child who died after a high voltage electrical shock. In both cases, layered dissection of the upper limb revealed fresh intramuscular hemorrhages in the skeletal muscles that could be topographically related to the path taken by the current through the body. Externally visible electric marks were present in both cases. The hemorrhages were most likely caused by current-induced tetanic muscle contractions, producing an internal muscle trauma with rupture of fibers and bleedings. In complex situations, such as inconspicuous marks or a complete lack of visible signs on the body, the finding may be helpful in solving the case in consideration of the case history and circumstances. The vitality, topography, and pattern of the hemorrhages are discussed in the light of the available literature. [ABSTRACT FROM AUTHOR]

Background: Patterns of opioid use vary, including prescribed use without aberrancy, limited aberrant use, and potential opioid use disorder (OUD). In clinical practice, similar opioid-related International Classification of Disease (ICD) codes are applied across this spectrum, limiting understanding of how groups vary by sociodemographic factors, comorbidities, and long-term risks. Objective: (1) Examine how Veterans assigned opioid abuse/dependence ICD codes vary at diagnosis and with respect to long-term risks. (2) Determine whether those with limited aberrant use share more similarities to likely OUD vs those using opioids as prescribed. Design: Longitudinal observational cohort study. Participants: National sample of Veterans categorized as having (1) likely OUD, (2) limited aberrant opioid use, or (3) prescribed, non-aberrant use based upon enhanced medical chart review. Main Measures: Comparison of sociodemographic and clinical factors at diagnosis and rates of age-adjusted mortality, non-fatal opioid overdose, and hospitalization after diagnosis. An exploratory machine learning analysis investigated how closely those with limited aberrant use resembled those with likely OUD. Key Results: Veterans (n = 483) were categorized as likely OUD (62.1%), limited aberrant use (17.8%), and prescribed, non-aberrant use (20.1%). Age, proportion experiencing homelessness, chronic pain, anxiety disorders, and non-opioid substance use disorders differed by group. All-cause mortality was high (44.2 per 1000 person-years (95% CI 33.9, 56.7)). Hospitalization rates per 1000 person-years were highest in the likely OUD group (831.5 (95% CI 771.0, 895.5)), compared to limited aberrant use (739.8 (95% CI 637.1, 854.4)) and prescribed, non-aberrant use (411.9 (95% CI 342.6, 490.4). The exploratory analysis reclassified 29.1% of those with limited aberrant use as having likely OUD with high confidence. Conclusions: Veterans assigned opioid abuse/dependence ICD codes are heterogeneous and face variable long-term risks. Limited aberrant use confers increased risk compared to no aberrant use, and some may already have OUD. Findings warrant future investigation of this understudied population. [ABSTRACT FROM AUTHOR]

Background: For patients with single sided deafness (SSD) or severe asymmetric sensorineural hearing loss (ASHL), cochlear implantation remains the only solution to restore bilateral hearing capacity. Prognostically, the duration of hearing loss in terms of audiological outcome is not yet clear. Therefore, the aim of this study was to retrospectively investigate the influence of subjective deafness duration on postoperative speech perception after cochlear implantation for SSD as well as its impact on quality of life. Materials and methods: The present study included a total of 36 adults aged 50.2 ± 15.5 years who underwent CI for SSD/ASHL at our clinic between 2010 and 2015. Patients were audiometrically assessed at 3 and 12–36 months postoperatively. Test results were correlated with self-reported duration of deafness. Quality of life was assessed by questionnaire. Results: Mean duration of deafness was 193.9 ± 185.7 months. The side-separated hearing threshold showed an averaged target range between 30 and 40 dB HL. Freiburg monosyllable test increased from 0% pre-operatively to 20% after 3 months (p = 0.001) and to 50% after 12–36 months (p = 0.002). There was a significant correlation between audiometric outcome and subjective deafness duration at 12–36 months postoperatively (r = − 0.564; p = 0.02) with a cutoff for open-set monosyllable recognition at a duration of deafness of greater than 408 months. Quality of life was significantly improved by CI. Conclusions: CI implantation in unilaterally deafened patients provides objective and subjective benefits. Duration of deafness is unlikely to be an independent negative predictive factor and thus should not generally be considered as contraindication. [ABSTRACT FROM AUTHOR]

The aim of this pilot study was to investigate the diagnostic potential of TMEM119 as a useful microglia-specific marker in combination with immunostainings for phagocytic function and infiltrating capacity of monocytes in cases of lethal monosubstance intoxications by morphine (MOR), methamphetamine (METH), and of ethanol-associated death (ETH) respectively. Human brain tissue samples were obtained from forensic autopsies of cases with single substance abuse (MOR, n = 8; ETH, n = 10; METH, n = 9) and then compared to a cohort of cardiovascular fatalities as controls (n = 9). Brain tissue samples of cortex, white matter, and hippocampus were collected and stained immunohistochemically with antibodies against TMEM119, CD68KiM1P, and CCR2. We could document the lowest density of TMEM119-positive cells in MOR deaths with highly significant differences to the control densities in all three regions investigated. In ETH and METH deaths, the expression of TMEM119 was comparable to cell densities in controls. The results indicate that the immunoreaction in brain tissue is different in these groups depending on the drug type used for abuse. [ABSTRACT FROM AUTHOR]

The German National Cohort (NAKO) is a multidisciplinary, population-based prospective cohort study that aims to investigate the causes of widespread diseases, identify risk factors and improve early detection and prevention of disease. Specifically, NAKO is designed to identify novel and better characterize established risk and protection factors for the development of cardiovascular diseases, cancer, diabetes, neurodegenerative and psychiatric diseases, musculoskeletal diseases, respiratory and infectious diseases in a random sample of the general population. Between 2014 and 2019, a total of 205,415 men and women aged 19–74 years were recruited and examined in 18 study centres in Germany. The baseline assessment included a face-to-face interview, self-administered questionnaires and a wide range of biomedical examinations. Biomaterials were collected from all participants including serum, EDTA plasma, buffy coats, RNA and erythrocytes, urine, saliva, nasal swabs and stool. In 56,971 participants, an intensified examination programme was implemented. Whole-body 3T magnetic resonance imaging was performed in 30,861 participants on dedicated scanners. NAKO collects follow-up information on incident diseases through a combination of active follow-up using self-report via written questionnaires at 2–3 year intervals and passive follow-up via record linkages. All study participants are invited for re-examinations at the study centres in 4–5 year intervals. Thereby, longitudinal information on changes in risk factor profiles and in vascular, cardiac, metabolic, neurocognitive, pulmonary and sensory function is collected. NAKO is a major resource for population-based epidemiology to identify new and tailored strategies for early detection, prediction, prevention and treatment of major diseases for the next 30 years. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate if the biomarkers myelin basic protein (MBP) and neurofilament-H (NF-H) yielded informative value in forensic diagnostics when examining cadaveric cerebrospinal fluid (CSF) biochemically via an enzyme-linked immunosorbent assay (ELISA) and comparing the corresponding brain tissue in fatal traumatic brain injury (TBI) autopsy cases by immunocytochemistry versus immunohistochemistry. In 21 trauma and 19 control cases, CSF was collected semi-sterile after suboccipital puncture and brain specimens after preparation. The CSF MBP (p = 0.006) and NF-H (p = 0.0002) levels after TBI were significantly higher than those in cardiovascular controls. Immunohistochemical staining against MBP and against NF-H was performed on cortical and subcortical samples from also biochemically investigated cases (5 TBI cases/5 controls). Compared to the controls, the TBI cases showed a visually reduced staining reaction against MBP or repeatedly ruptured neurofilaments against NF-H. Immunocytochemical tests showed MBP-positive phagocytizing macrophages in CSF with a survival time of > 24 h. In addition, numerous TMEM119-positive microglia could be detected with different degrees of staining intensity in the CSF of trauma cases. As a result, we were able to document that elevated levels of MBP and NF-H in the CSF should be considered as useful neuroinjury biomarkers of traumatic brain injury. [ABSTRACT FROM AUTHOR]

Experimental nephrotic syndrome leads to activation of the epithelial sodium channel (ENaC) by proteolysis and promotes renal sodium retention. The membrane-anchored serine protease prostasin (CAP1/PRSS8) is expressed in the distal nephron and participates in proteolytic ENaC regulation by serving as a scaffold for other serine proteases. However, it is unknown whether prostasin is also involved in ENaC-mediated sodium retention of experimental nephrotic syndrome. In this study, we used genetically modified knock-in mice with Prss8 mutations abolishing its proteolytic activity (Prss8-S238A) or prostasin activation (Prss8-R44Q) to investigate the development of sodium retention in doxorubicin-induced nephrotic syndrome. Healthy Prss8-S238A and Prss8-R44Q mice had normal ENaC activity as reflected by the natriuretic response to the ENaC blocker triamterene. After doxorubicin injection, all genotypes developed similar proteinuria. In all genotypes, urinary prostasin excretion increased while renal expression was not altered. In nephrotic mice of all genotypes, triamterene response was similarly increased, consistent with ENaC activation. As a consequence, urinary sodium excretion dropped in all genotypes and mice similarly gained body weight by + 25 ± 3% in Prss8-wt, + 20 ± 2% in Prss8-S238A and + 28 ± 3% in Prss8-R44Q mice (p = 0.16). In Western blots, expression of fully cleaved α- and γ-ENaC was similarly increased in nephrotic mice of all genotypes. In conclusion, proteolytic ENaC activation and sodium retention in experimental nephrotic syndrome are independent of the activation of prostasin and its enzymatic activity and are consistent with the action of aberrantly filtered serine proteases or proteasuria. [ABSTRACT FROM AUTHOR]

Traumatic brain injury (TBI) is a major cause of death and its accurate diagnosis is an important concern of daily forensic practice. However, it can be challenging to diagnose TBI in cases where macroscopic signs of the traumatic head impact are lacking and little is known about the circumstances of death. In recent years, several post-mortem studies investigated the possible use of biomarkers for providing objective evidence for TBIs as the cause of death or to estimate the survival time and time since death of the deceased. This work systematically reviewed the available scientific literature on TBI-related biomarkers to be used for forensic purposes. Post-mortem TBI-related biomarkers are an emerging and promising resource to provide objective evidence for cause of death determinations as well as survival time and potentially even time since death estimations. This literature review of forensically used TBI-biomarkers revealed that current markers have low specificity for TBIs and only provide limited information with regards to survival time estimations and time since death estimations. Overall, TBI fatality-related biomarkers are largely unexplored in compartments that are easily accessible during autopsies such as urine and vitreous humor. Future research on forensic biomarkers requires a strict distinction of TBI fatalities from control groups, sufficient sample sizes, combinations of currently established biomarkers, and novel approaches such as metabolomics and mi-RNAs. [ABSTRACT FROM AUTHOR]

In the last few years, quantitative analysis of metabolites in body fluids using LC/MS has become an established method in laboratory medicine and toxicology. By preparing metabolite profiles in biological specimens, we are able to understand pathophysiological mechanisms at the biochemical and thus the functional level. An innovative investigative method, which has not yet been used widely in the forensic context, is to use the clinical application of metabolomics. In a metabolomic analysis of 41 samples of postmortem cerebrospinal fluid (CSF) samples divided into cohorts of four different causes of death, namely, cardiovascular fatalities, isoIated torso trauma, traumatic brain injury, and multi-organ failure, we were able to identify relevant differences in the metabolite profile between these individual groups. According to this preliminary assessment, we assume that information on biochemical processes is not gained by differences in the concentration of individual metabolites in CSF, but by a combination of differently distributed metabolites forming the perspective of a new generation of biomarkers for diagnosing (fatal) TBI and associated neuropathological changes in the CNS using CSF samples. [ABSTRACT FROM AUTHOR]

The aim of the present study was a refined analysis of neuroinflammation including TMEM119 as a useful microglia-specific marker in forensic assessments of traumatic causes of death, e.g., traumatic brain injury (TBI). Human brain tissue samples were obtained from autopsies and divided into cases with lethal TBI (n = 25) and subdivided into three groups according to their trauma survival time and compared with an age-, gender-, and postmortem interval-matched cohort of sudden cardiovascular fatalities as controls (n = 23). Brain tissue samples next to cortex contusions and surrounding white matter as well as samples of the ipsilateral uninjured brain stem and cerebellum were collected and stained immunohistochemically with antibodies against TMEM119, CD206, and CCR2. We could document the highest number of TMEM119-positive cells in acute TBI death with highly significant differences to the control numbers. CCR2-positive monocytes showed a significantly higher cell count in the cortex samples of TBI cases than in the controls with an increasing number of immunopositive cells over time. The number of CD206-positive M2 microglial cells increased survival time-dependent. After 3 days of survival, the cell number increased significantly in all four regions investigated compared with controls. In sum, we validate a specific and robustly expressed as well as fast reacting microglia marker, TMEM119, which distinguishes microglia from resident and infiltrating macrophages and thus offers a great potential for the estimation of the minimum survival time after TBI. [ABSTRACT FROM AUTHOR]

Purpose: An adult version of an app giving users the control over the level of the volume, microphone directionality and noise reduction was adapted for children. The main purpose of this study was to evaluate the effect of changes made to microphone directionality and noise reduction in the myPhonak Junior (the app) on Speech intelligibility in challenging listening environments in children and teens.The randomized, non-blinded interventional study with a single group of subjects involved two study visits with a home trial in-between. In the final study session speech assessment in noise was conducted in three different, randomly assigned conditions: default mode (Autosense Sky OS), preffered (self-adjusted) and the extreme condition. Questionnaire based assessment was conducted to assess the subjective benefit of using the app in different daily situations.The best scores (speech results in noise) were achieved with the preferred setting and the default Autosense Sky OS setting was significantly better than the extreme setting. The self-reported benefit through the questionnaire indicates significantly better result when adjusting the hearing aids through the app.The app is an easy-to-use way of controlling the level of noise reduction and the beam forming for children 11 years and older. It has the potential to help customizing the hearing aids beyond the default setting and helping to improve speech understanding in noise.Methods: An adult version of an app giving users the control over the level of the volume, microphone directionality and noise reduction was adapted for children. The main purpose of this study was to evaluate the effect of changes made to microphone directionality and noise reduction in the myPhonak Junior (the app) on Speech intelligibility in challenging listening environments in children and teens.The randomized, non-blinded interventional study with a single group of subjects involved two study visits with a home trial in-between. In the final study session speech assessment in noise was conducted in three different, randomly assigned conditions: default mode (Autosense Sky OS), preffered (self-adjusted) and the extreme condition. Questionnaire based assessment was conducted to assess the subjective benefit of using the app in different daily situations.The best scores (speech results in noise) were achieved with the preferred setting and the default Autosense Sky OS setting was significantly better than the extreme setting. The self-reported benefit through the questionnaire indicates significantly better result when adjusting the hearing aids through the app.The app is an easy-to-use way of controlling the level of noise reduction and the beam forming for children 11 years and older. It has the potential to help customizing the hearing aids beyond the default setting and helping to improve speech understanding in noise.Results: An adult version of an app giving users the control over the level of the volume, microphone directionality and noise reduction was adapted for children. The main purpose of this study was to evaluate the effect of changes made to microphone directionality and noise reduction in the myPhonak Junior (the app) on Speech intelligibility in challenging listening environments in children and teens.The randomized, non-blinded interventional study with a single group of subjects involved two study visits with a home trial in-between. In the final study session speech assessment in noise was conducted in three different, randomly assigned conditions: default mode (Autosense Sky OS), preffered (self-adjusted) and the extreme condition. Questionnaire based assessment was conducted to assess the subjective benefit of using the app in different daily situations.The best scores (speech results in noise) were achieved with the preferred setting and the default Autosense Sky OS setting was significantly better than the extreme setting. The self-reported benefit through the questionnaire indicates significantly better result when adjusting the hearing aids through the app.The app is an easy-to-use way of controlling the level of noise reduction and the beam forming for children 11 years and older. It has the potential to help customizing the hearing aids beyond the default setting and helping to improve speech understanding in noise.Conclusion: An adult version of an app giving users the control over the level of the volume, microphone directionality and noise reduction was adapted for children. The main purpose of this study was to evaluate the effect of changes made to microphone directionality and noise reduction in the myPhonak Junior (the app) on Speech intelligibility in challenging listening environments in children and teens.The randomized, non-blinded interventional study with a single group of subjects involved two study visits with a home trial in-between. In the final study session speech assessment in noise was conducted in three different, randomly assigned conditions: default mode (Autosense Sky OS), preffered (self-adjusted) and the extreme condition. Questionnaire based assessment was conducted to assess the subjective benefit of using the app in different daily situations.The best scores (speech results in noise) were achieved with the preferred setting and the default Autosense Sky OS setting was significantly better than the extreme setting. The self-reported benefit through the questionnaire indicates significantly better result when adjusting the hearing aids through the app.The app is an easy-to-use way of controlling the level of noise reduction and the beam forming for children 11 years and older. It has the potential to help customizing the hearing aids beyond the default setting and helping to improve speech understanding in noise. [ABSTRACT FROM AUTHOR]

Proteolytic activation of the epithelial sodium channel (ENaC) by aberrantly filtered serine proteases is thought to contribute to renal sodium retention in nephrotic syndrome. However, the identity of the responsible proteases remains elusive. This study evaluated factor VII activating protease (FSAP) as a candidate in this context. We analyzed FSAP in the urine of patients with nephrotic syndrome and nephrotic mice and investigated its ability to activate human ENaC expressed in Xenopus laevis oocytes. Moreover, we studied sodium retention in FSAP-deficient mice (Habp2−/−) with experimental nephrotic syndrome induced by doxorubicin. In urine samples from nephrotic humans, high concentrations of FSAP were detected both as zymogen and in its active state. Recombinant serine protease domain of FSAP stimulated ENaC-mediated whole-cell currents in a time- and concentration-dependent manner. Mutating the putative prostasin cleavage site in γ-ENaC (γRKRK178AAAA) prevented channel stimulation by the serine protease domain of FSAP. In a mouse model for nephrotic syndrome, active FSAP was present in nephrotic urine of Habp2+/+ but not of Habp2−/− mice. However, Habp2−/− mice were not protected from sodium retention compared to nephrotic Habp2+/+ mice. Western blot analysis revealed that in nephrotic Habp2−/− mice, proteolytic cleavage of α- and γ-ENaC was similar to that in nephrotic Habp2+/+ animals. In conclusion, active FSAP is excreted in the urine of nephrotic patients and mice and activates ENaC in vitro involving the putative prostasin cleavage site of γ-ENaC. However, endogenous FSAP is not essential for sodium retention in nephrotic mice. [ABSTRACT FROM AUTHOR]

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Phytopathogenic fungi are known to secrete specific proteins which act as virulence factors and promote host colonization. Some of them are enzymes with plant cell wall degradation capability, like pectate lyases (Pls). In this work, we examined the involvement of Pls in the infection process of Magnaporthe oryzae, the causal agent of rice blast disease. From three Plgenes annotated in the M. oryzae genome, only transcripts of MoPL1 considerably accumulated during the infection process with a peak at 72 h post inoculation. Both, gene deletion and a constitutive expression of MoPL1 in M. oryzae led to a significant reduction in virulence. By contrast, mutants that constitutively expressed an enzymatic inactive version of MoPl1 did not differ in virulence compared to the wild type isolate. This indicates that the enzymatic activity of MoPl1 is responsible for diminished virulence, which is presumably due to degradation products recognized as danger associated molecular patterns (DAMPs), which strengthen the plant immune response. Microscopic analysis of infection sites pointed to an increased plant defense response. Additionally, MoPl1 tagged with mRFP, and not the enzymatic inactive version, focally accumulated in attacked plant cells beneath appressoria and at sites where fungal hyphae transverse from one to another cell. These findings shed new light on the role of pectate lyases during tissue colonization in the necrotrophic stage of M. oryzae's life cycle. [ABSTRACT FROM AUTHOR]

Background: There has been a reduction in BZD prescribing in the Veterans Affairs (VA) health care system since 2013. It is unknown whether the decline in VA-dispensed BZDs has been offset by Medicare Part D prescriptions. Objectives: To examine (1) whether, accounting for Part D, declines in BZD prescribing to older Veterans remain; (2) patient characteristics associated with obtaining BZDs outside VA and facility variation in BZD source (VA only, VA and Part D, Part D only). Design: Retrospective cohort study with mixed effects multinomial logistic model examining characteristics associated with BZD source. Patients: A total of 1,746,278 Veterans aged ≥65 enrolled in VA and Part D, 2013–2017. Main Measures: BZD prescription prevalence and source. Key Results: From January 2013 to June 2017, the quarterly prevalence of older Veterans with Part D filling BZD prescriptions through the VA declined from 5.2 to 3.1% (p<0.001) or, accounting for Part D, from 10.0 to 7.7% (p<0.001). Among those prescribed BZDs between July 2016 and June 2017, 37.0%, 10.2%, and 52.8% received prescriptions from VA only, both VA and Part D, or Part D only, respectively. Older age was associated with higher odds of obtaining BZDs through Part D (e.g., compared to those 65–74, Veterans ≥85 had adjusted odds ratio [AOR] for Part D vs. VA only of 1.8 [95% highest posterior density interval (HPDI), 1.69, 1.86]). Veterans with substance use disorders accounted for few BZD prescriptions from any source but were associated with higher odds of prescriptions through Part D (e.g., alcohol use disorder AOR for Part D vs. VA alone: 1.9 [95% HPDI, 1.63, 2.11]) Conclusions: The decline in BZD use by older Veterans with Part D coverage remained after accounting for Part D, but the majority of BZD prescriptions came from Medicare. Further reducing BZD prescribing to older Veterans should consider prescriptions from community sources. [ABSTRACT FROM AUTHOR]

Adoption of certain behavioral and social routines that organize and structure the home environment may help families navigate the challenges presented by the COVID-19 pandemic. The current cross-sectional study aimed to assess family routines prior to and during the COVID-19 pandemic and examine associations with individual and family well-being. Using a national sample, 300 caregivers of children ages 6-18 were surveyed using Amazon Mechanical Turk platform during the first three months of COVID-19 pandemic in the United States. Caregivers reported on family demographics, COVID-19-related stress, engagement in family routines (prior to and during the COVID-19 pandemic), stress mindset, self-efficacy, and family resiliency. Overall, families reported engaging in fewer routines during the COVID-19 pandemic compared to prior to the pandemic. COVID-19-related stress was highest in low-income families, families of healthcare workers, and among caregivers who had experienced the COVID-19 virus. Moreover, COVID-19-related stress was negatively related to self-efficacy, positively related to an enhancing stress mindset, and negatively related to family resilience. Engagement in family routines buffered relations between COVID-19-related stress and family resilience, such that COVID-19-related stress was not associated with lower family resilience among families that engaged in high levels of family routines. Results suggest that family routines were challenging to maintain in the context of the COVID-19 pandemic, but were associated with better individual and family well-being during this period of acute health, economic, and social stress. Highlights: Families reported engaging in fewer routines during the COVID-19 pandemic, when compared to prior to the pandemic. Families reported significant reductions in child bedtime routines and screen time limitations during the COVID-19 pandemic, when compared to prior to the pandemic. Engagement in family routines buffered the impact of stress on family resilience during the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Background: Barth syndrome (BTHS) is a rare X-linked condition resulting in cardiomyopathy, however; the effects of BTHS on myocardial substrate metabolism and its relationships with cardiac high-energy phosphate metabolism and left ventricular (LV) function are unknown. We sought to characterize myocardial glucose, fatty acid (FA), and leucine metabolism in BTHS and unaffected controls and examine their relationships with cardiac high-energy phosphate metabolism and LV function.Methods/results: Young adults with BTHS (n = 14) and unaffected controls (n = 11, Control, total n = 25) underwent bolus injections of 15O-water and 1-11C-glucose, palmitate, and leucine and concurrent positron emission tomography imaging. LV function and cardiac high-energy phosphate metabolism were examined via echocardiography and 31P magnetic resonance spectroscopy, respectively. Myocardial glucose extraction fraction (21 ± 14% vs 10 ± 8%, P = .03) and glucose utilization (828.0 ± 470.0 vs 393.2 ± 361.0 μmol·g-1·min-1, P = .02) were significantly higher in BTHS vs Control. Myocardial FA extraction fraction (31 ± 7% vs 41 ± 6%, P < .002) and uptake (0.25 ± 0.04 vs 0.29 ± 0.03 mL·g-1·min-1, P < .002) were significantly lower in BTHS vs Control. Altered myocardial metabolism was associated with lower cardiac function in BTHS.Conclusions: Myocardial substrate metabolism is altered and may contribute to LV dysfunction in BTHS. Clinical Trials #: NCT01625663. [ABSTRACT FROM AUTHOR]

Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although comprehensive in terms of longitudinal characterization of disease development and progression for a potentially large number of patients, population-based inference using these datasets require thoughtful modifications to sample selection and analytic strategies relative to other types of studies. Along with complex selection bias and missing data issues, claims-based studies are purely observational, which limits effective understanding and characterization of the treatment differences between groups being compared. All these issues contribute to a crisis in reproducibility and replication of comparative findings using medical claims. This paper offers practical guidance to the analytical process, demonstrates methods for estimating causal treatment effects with propensity score methods for several types of outcomes common to such studies, such as binary, count, time to event and longitudinally varying measures, and also aims to increase transparency and reproducibility of reporting of results from these investigations. We provide an online version of the paper with readily implementable code for the entire analysis pipeline to serve as a guided tutorial for practitioners. The online version can be accessed at https://rydaro.github.io/. The analytic pipeline is illustrated using a sub-cohort of patients with advanced prostate cancer from the large Clinformatics TM Data Mart Database (OptumInsight, Eden Prairie, Minnesota), consisting of 73 million distinct private payer insures from 2001 to 2016. [ABSTRACT FROM AUTHOR]

Due to its protected anatomical location, cerebrospinal fluid (CSF) is a very stable fluid which undergoes comparatively little change in the early post-mortem phase. While many immunohistochemical markers already established for clinical diagnostic issues in tissue samples obtained by biopsy could meanwhile be translated also to post-mortem tissue, no systematic immunocytochemical investigations have generally been conducted on post-mortem body fluids and for CSF specifically, have not been established at all. CSF as the fluid directly surrounding the brain should also be examined to allow a more detailed characterization of processes in the central nervous system. Comparing traumatized tissue and CSF can complete forensic assessment and complement neuropathological evaluation. [ABSTRACT FROM AUTHOR]

Background: Existing research suggests that greater sleep variability may increase risk for weight gain. College often marks a transition to a less consistent daily schedule, which may adversely impact sleep routines and further increase risk for weight gain. The current study is among the first to explore relations between nighttime sleep variability and daytime sleep (napping) and body weight among first-year college students. Methods: Using daily diary methods, first-year college students (N = 307; 84.7% female) self-reported their sleep for seven days. Several indices were created to capture sleep variability for reported bedtime, wake time, and sleep duration, including weekday versus weekend differences (WvW), day to day differences (D2D), and overall standard deviation (SD). Napping was also assessed. Based on body mass index (BMI), individuals were categorized as underweight, healthy weight, overweight, and obese. Results: Across indices, students' sleep varied over an hour on average across the week. Hierarchical regressions revealed that greater differences in wake time D2D, wake time SD, and sleep duration WvW were all associated with higher BMI, after accounting for gender, depressive symptoms, and sleep duration. Longer napping was also associated with higher BMI, using the same covariates. Finally, greater sleep variability was reported by overweight and obese than healthy weight individuals. Conclusion: These findings suggest that sleep variability, particularly wake times and napping may be important modifiable sleep behaviors to investigate in future studies. More longitudinal research is needed to explore relations between multiple facets of sleep variability and weight gain, including possible mechanisms. [ABSTRACT FROM AUTHOR]

Despite the growing body of literature on how digital technologies impact child well-being, previous research has provided little evidence on recent digital trends. This paper examines the patterns and effects of digital use on child socioemotional well-being across two cohorts of children grown up ten years apart during the 'digital age': the 1998 cohort (interviewed in 2007/08) and the 2008 cohort (interviewed in 2017/18). Multivariate linear regression models were conducted for these two cohorts from the Growing Up in Ireland (GUI) study, a multi-cohort longitudinal study with rich comparable data on a large sample of 9-year olds (N = 13,203). Results show that (i) in 2017/18 children were more active in digital devices and social media, while in 2007/2008 children spent more time watching TV and adopted less diversified forms of media engagement; (ii) spending more than 3 daily hours on TV/digital activities was associated with significant declines in child socioemotional well-being, while such effects were stronger in 2017/18 than in 2007/08; (iii) media engagement (but not other forms of digital engagement) was associated with moderate declines in socioemotional well-being, both in 2007/08 and in 2017/18; (iv) while children's media and digital engagement differed by the child gender and socioeconomic background, none of these variables moderated the effects of digital use on children's socioemotional well-being, neither in 2007/08 nor in 2017/18. Overall, the study reveals persistence, but also some important changes, in recent trends on children's digital use and its impact on socioemotional well-being in Ireland. [ABSTRACT FROM AUTHOR]

Wheat blast caused by Magnaporthe oryzae pv. Triticum is an upcoming threat to wheat cultivation worldwide. The disease crossing over to wheat first gained attention in South America, with increasing interest coming from its more recent appearance in the big wheat-growing areas of Asia. The increasing economic relevance of the disease and the lack of genetic resistance in current wheat breeding material, besides fungicide resistance already present in fungal pathogen populations, highlighted the need to evaluate the potential of isotianil as an alternative plant protection measure. Isotianil is already registered in Asia for the protection of rice against M. oryzae, but because the agronomic practices and disease development of blast differ between rice and wheat, the efficacy of isotianil against wheat blast was hard to predict. Testing isotianil in the currently available formulations, applied either as seed treatment or soil drench, resulted in a significant reduction of disease severity. The efficacy was comparably high, on different wheat cultivars and using several fungal isolates with different degrees of virulence. Microscopic analyses revealed that isotianil treatment can prevent invasive growth of the pathogen. No phytotoxicity from isotianil treatment was observed on wheat plants. Importantly, isotianil not only protects wheat plants at the seedling stage but also on spikes thereby preventing losses due to this most severe disease syndrome. In summary, the results showed the high potential of isotianil to protect against wheat blast. [ABSTRACT FROM AUTHOR]

Evidence-based treatment of opioid use disorder, the prevention of opioid overdose and other opioid-related harms, and safe and effective pain management are priorities for the Veterans Health Administration (VHA). The VHA Office of Health Services Research and Development hosted a State-of-the-Art Conference on "Effective Management of Pain and Addiction: Strategies to Improve Opioid Safety" on September 10–11, 2019. This conference convened a multidisciplinary group to discuss and achieve consensus on a research agenda and on implementation and policy recommendations to improve opioid safety for Veterans. Participants were organized into three workgroups: (1) managing opioid use disorder; (2) Long-term opioid therapy and opioid tapering; (3) managing co-occurring pain and substance use disorder. Here we summarize the implementation and policy recommendations of each workgroup and highlight important cross-cutting issues related to telehealth, care coordination, and stepped care model implementation. [ABSTRACT FROM AUTHOR]

Purpose: The use of reverse shoulder arthroplasty (RSA) to treat complex humerus fractures is increasing, especially in older, osteoporotic patients. Refixation and tuberosity healing are needed to achieve an optimal range of motion (ROM), external rotation, active forward elevation, and patient satisfaction. Proper healing has been reported, however, in only 40–84% of cases. Our study's aim was to describe a simple, reproducible fixation technique designed to improve tuberosity healing. Methods: We included 30 patients with acute proximal humerus fractures undergoing RSA (Global Unite Reverse Fracture, DePuy Synthes, Warsaw, IN, USA) with tuberosity reattachment. The humerus stem was cemented in 24 cases. A standardized suture technique with two fiber tapes was used to reattach tuberosities. Clinical and radiological parameters, which were collected one year post-operatively, included ROM, pain level, Constant scores, subjective shoulder value (SSV), and tuberosity healing. Results: The mean age of the patients was 79.3 years (± 7; range 65–92), and the tuberosity healing rate was 90.0% (27 of 30). Two patients showed migration (one nonunion, one malunion), and another had complete resorption after an initial period of proper healing. Radiolucent lines around the humerus stem occurred in one case, and three patients had scapular notching. The mean SSV was 86% (± 11; range 60–100), the Constant score was 72 (± 10.3; range 48–92), the active forward flexion was 140° (± 14.3; range 115–165), and external rotation was 23° (± 16.5; range 0–50). Conclusions: This reattachment technique, which is simple and reproducible, achieved a higher tuberosity healing rate than previously published rates. [ABSTRACT FROM AUTHOR]

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In this casuistry, two accidents from Germany and Switzerland are presented that happened during the shot of recoilless anti-tank weapons. In both cases, the injuries led to the death of two soldiers: A 22-year-old soldier in Germany was struck by the counter mass of a so-called Davis gun which had been fired by a comrade during a firing exercise; he died from his severe injuries, especially in the abdominal part of the body. As a peculiarity of the wound morphology, it was found to be a thick-layered, metallic, gray material in the wound cavity, which corresponded to the material of the counter mass that was ejected opposite to the shooting direction. The other case took place in Switzerland, where a 24-year-old soldier was seriously injured during an exercise with portable anti-tank rockets. At the time the shot was fired, he stood behind the launcher and was hit by the propulsion jet of the rocket motor. He died as well from his severe injuries, which were located at the chest done by the gas jet and by the very high pressure. In both cases, two different causes of death were present: massive blunt violence in the first case versus a jet of hot gases of very high speed and temperature in the second case. [ABSTRACT FROM AUTHOR]

Organophosphorus compounds, such as chemical warfare nerve agents and pesticides, are known to cause neurological damage. This study measured nerve agent-related neuropathology and determined whether quantitative T2 MRI could be used as a biomarker of neurodegeneration. Quantitative T2 MRI was performed using a 9.4 T MRI on rats prior to and following soman exposure. T2 images were taken at least 24 h prior, 1 h and 18–24 h after soman exposure. Rats were pre- and post-treated with HI-6 dimethanesulfonate and atropine methyl nitrate. A multicomponent T2 acquisition and analysis was performed. Brains were stained with Fluoro-Jade C to assess neurodegeneration. Rats exposed to soman developed behavioral expression of electrographic seizures. At 18–24 h after soman exposure, significant increases in T2, a possible marker of edema, were found in multiple regions. The largest changes were in the piriform cortex (before: 47.7 ± 1.4 ms; 18–24 h: 82.3 ± 13.4 ms). Fluoro-Jade C staining showed significant neurodegeneration 18–24 h post exposure. The piriform cortex had the strongest correlation between the change in relaxation rate and percent neurodegeneration (r = 0.96, p < 0.001). These findings indicate there is regionally specific neurodegeneration 24 h after exposure to soman. The high correlation between T2 relaxivity and histopathology supports the use of T2 as a marker of injury. [ABSTRACT FROM AUTHOR]

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Background: Prescribing naloxone to patients is a key strategy to prevent opioid overdoses, but little is known about the reach of naloxone prescribing.Objective: Determine patient factors associated with receiving naloxone and trends over time in patients with key overdose risk factors.Design: Retrospective observational study.Participants: Using the Clinformatics DataMart, a US-wide health insurance claims dataset, we compared adults who received opioids and naloxone (opioid+naloxone) from January 2014 to June 2017 with adults who received opioids without naloxone (opioids only), matched on gender, age ± 5 years, month/year of opioid fill, and number of opioid claims.Main Measures: Key patient-level opioid overdose risk factors included receipt of high-dosage opioids, concurrent benzodiazepines, history of opioid and other substance use disorders, and history of opioid overdose.Results: We included 3963 opioid+naloxone and 19,815 opioid only patients. Key factors associated with naloxone fills included high opioid daily dosage (50 to < 90 morphine milligram equivalents (MME): AOR = 2.43, 95% CI 2.15-2.76 and ≥ 90 MME: AOR = 3.94, 95% CI 3.47-4.46; reference: < 50 MME), receiving concurrent benzodiazepines (AOR = 1.27, 95% CI 1.16-1.38), and having a diagnosis of opioid use disorder (AOR = 1.56, 95% CI 1.40-1.73). History of opioid overdose was not associated with naloxone (AOR = 0.92, 95% CI 0.74-1.15). The percent of patients receiving naloxone increased, yet less than 2% of patients in any of the key overdose risk factor groups received naloxone by the last 6 months of the study period.Conclusions: Naloxone prescribing has increased and was more likely to be co-prescribed to patients with some risk factors for overdose. However, overall prescribing remains minimal. Additional efforts are needed across health systems to increase naloxone prescribing for patients at risk for opioid overdose. [ABSTRACT FROM AUTHOR]

Objective: To develop a new, German, age-appropriate speech audiometry test for children, by using 26 nouns that are most likely part of the lexicon of 2-year-olds. The test is a picture-pointing task with a four-option non-forced choice method. Materials and methods: In total, 179 children aged 2;11 to 6;9 y were included for standardizing and validating the speech test. Of these, 51 had a hearing impairment in both ears ranging up to 90 dB hearing level (HL). The normal-hearing collective was divided into three groups according to age. For each group, the speech reception threshold (SRT) and the slope of the psychometric function of intelligibility were determined. For validation, the test-retest reliability was measured in 85 ears, and the correlation between the pure tone average (PTA) at 0.5, 1, 2, and 4 kHz and the SRT was measured in 86 ears. Results: The sound spectrum of the 26 items was in good accordance with the international long-term speech spectrum, and the relative frequency of phonemes matched the distribution of the 50 more frequent German phonemes. The SRTs ranged from 24.6 ± 0.6 dB sound pressure level (SPL) for the oldest group (> 5.5 y) to 29.3 ± 1.3 dB SPL for the youngest group (< 4.25 y). The slopes of the psychometric function ranged from 4.3 ± 0.5%/dB for the oldest group to 2.6 ± 0.4%/dB for the youngest. The test and retest showed good correlation (r = 0.89, p < 0.0001) as did the PTA and SRT (r = 0.84, p < 0.0001). Conclusion: The newly developed Mainz speech-test effectively measures age-related speech perception from the age of three years. [ABSTRACT FROM AUTHOR]

Blood-brain barrier (BBB) integrity is one of the important elements of central nervous system (CNS) homeostasis. MicroRNAs (miRs) have been demonstrated to play a role in many CNS disorders such as stroke and traumatic brain injury. MiR-212/132 are highly expressed in the CNS but their role at the BBB has not been characterized yet. Thus, we analyzed the expression of miR-212/132 in hypoxic mouse and human brain microvascular endothelial cells (BMEC) as well as in posttraumatic mouse and human brain tissue and serum exosomes. MiR-212/132 expression was detected in brain capillaries by in situ hybridization and was increased up to ten times in hypoxic BMEC. Over-expression of pre-miR-212/132 in BMEC decreased barrier properties and reduced migration of BMEC in the wound healing assay. We identified and validated tight junction proteins claudin-1 (Cldn1), junctional adhesion molecule 3 (Jam3), and tight junction-associated protein 1 (Tjap1) as potential miR-212/132 targets. Over-expression of miRs led to a decrease in mRNA and protein expression of Cldn1, Jam3, and Tjap1, which could be rescued by a respective anti-miR. In conclusion, our study identifies miR-212/132 as critical players at the hypoxic BBB. In addition, we propose three new direct miR-212/132 targets to be involved in miR-212/132-mediated effects on BBB properties. [ABSTRACT FROM AUTHOR]

Purpose: The purpose of this study was to calculate suicide rates and identify correlates of risk in the year following discharge from acute Veterans Health Administration psychiatric inpatient units among male veterans discharged from 2005 to 2010 (fiscal years).Methods: Suicide rates and standardized mortality ratios were calculated. Descriptive analyses were used to describe suicides and non-suicides and provide base rates for interpretation, and unadjusted and adjusted proportional hazard models were used to identify correlates of suicide.Results: From 2005 to 2010, 929 male veterans died by suicide in the year after discharge and the suicide rate was 297/100,000 person-years (py). The suicide rate significantly increased from 234/100,000 py (95% CI = 193-282) in 2005 to 340/100,000 py (95% CI = 292-393) in 2008, after which it plateaued. Living in a rural setting, HR (95% CI) = 1.20 (1.05, 1.36), and being diagnosed with a mood disorder such as major depression, HR (95% CI) = 1.60 (1.36, 1.87), or other anxiety disorder, HR (95% CI) = 1.52 (1.24, 1.87), were associated with increased risk for suicide.Conclusions: Among male veterans, the suicide rate in the year after discharge from acute psychiatric hospitalization increased from 2005 to 2008, after which it plateaued. Prevention efforts should target psychiatrically hospitalized veterans who live in rural settings and/or are diagnosed with mood or other anxiety disorders. [ABSTRACT FROM AUTHOR]

Purpose: Wideband-tympanometry (WBT) could give more informative data about the tympanic condition than the conventional tympanometry. In the actual literature, the clinical profit of wideband-tympanometry in pediatric audiological settings is not well evaluated. The aim of this study was to analyze the additional clinical benefit. Methods: 150 children (281 ears) with normal hearing, at the age from 11 days up to 14;10 years, checked with pure tone audiometry or auditory brainstem responses (ABR) participated in this retrospective study. We divided in four age ranges (≤ 6 month; > 6 month ≤ 3 years; > 3 years ≤ 11 years; > 11 years). All children were evaluated with ENT examination including ear microscopy, conventional 226-Hz or 1000-Hz tympanometry and WBT. Ear canal volumes were determined. Results: Compared with literature data, our patients aged ≤ 3 years showed smaller mean ear canal volumes (≤ 4 ml). We found a good statistical correlation between the WBT-results and 1000-Hz tympanometry but a rare correlation between WBT-results and ear microscopic findings. In the patients with pathologic ear microscopic results in all groups of age, a significant reduction of WBT-absorbance in 1000 Hz and 2000 Hz was found. Conclusions: This study confirms that WBT collects additive data to detect the correct middle ear status. In pediatric audiology, WBT is an additional useful method to value middle ear problems and to analyze the character of infantile hearing loss. Standard guidelines for the interpretation of the pediatric population are needed. Hence, it will be necessary to determine these findings in a larger number of infantile ears. [ABSTRACT FROM AUTHOR]

Adolescents with high-functioning Autism Spectrum Disorder (HFASD) experience difficulties with socio-emotional adjustment, including compromised friendships, feelings of loneliness, and depression. Using a sample of 127 adolescents with HFASD and their parents, this study is first to examine: (1) relations between organized activity (OA) involvement and adjustment and (2) whether these relations were moderated by social impairment and executive functions. Results indicated that greater intensity, breadth, and academic OA involvement were associated with fewer depressive symptoms. OA intensity was also associated with less loneliness. For adolescents with better emotional control, greater intensity was associated with better friendship quality. Results suggest that for adolescents with HFASD, more involvement in OA is associated with better socio-emotional adjustment even after accounting for risk factors. [ABSTRACT FROM AUTHOR]

In many forensic cases, the existence of a traumatic brain injury (TBI) is an essential factor, and the determination of the survival time is nearly as important as the determination of whether or not a trauma exists. Since it is known that glucose uptake increases in injured brain cells in order to perpetuate the neuronal integrity, this study focuses on the pathomechanism of brain glucose supply via sodium/glucose cotransporters 1 and 2 (SGLT1, SGLT2) following traumatization. Human cerebrum tissue of male and female individuals who died following TBI was taken from the contusional and contralateral regions, as well as from individuals deceased due to cardiac arrest (control group). Total SGLT1 and SGLT2 protein expression was analyzed by immunoblotting comparing injured and non-injured tissue. The immunoreactivity in contusional cerebral cortex region began to increase 3 to 7 h following traumatization. We found that both SGLT1 and SGLT2 protein expression increased significantly 37 h post-injury compared to the control group. SGLT1 rose significantly at 52 h post-injury and peaked significantly at 72 h, while SGLT2 rose significantly at 52 and 72 h after injury. By compiling these data, we predict a standard operator via SGLT expression as a comparative expression assertion to determine post-injury survival time for unknown cases. Our result suggests that SGLT1 and SGLT2 protein expression may be useful in forensic practice as an effective target to analyze the existence of a TBI and to determine the time of the traumatization. [ABSTRACT FROM AUTHOR]