Prior differences in previous trauma exposure primarily drive the observed racial/ethnic differences in posttrauma depression and anxiety following a recent trauma.

BACKGROUND: Racial and ethnic groups in the USA differ in the prevalence of posttraumatic stress disorder (PTSD). Recent research however has not observed consistent racial/ethnic differences in posttraumatic stress in the early aftermath of trauma, suggesting that such differences in chronic PTSD rates may be related to differences in recovery over time. METHODS: As part of the multisite, longitudinal AURORA study, we investigated racial/ethnic differences in PTSD and related outcomes within 3 months after trauma. Participants (n = 930) were recruited from emergency departments across the USA and provided periodic (2 weeks, 8 weeks, and 3 months after trauma) self-report assessments of PTSD, depression, dissociation, anxiety, and resilience. Linear models were completed to investigate racial/ethnic differences in posttraumatic dysfunction with subsequent follow-up models assessing potential effects of prior life stressors. RESULTS: Racial/ethnic groups did not differ in symptoms over time; however, Black participants showed reduced posttraumatic depression and anxiety symptoms overall compared to Hispanic participants and White participants. Racial/ethnic differences were not attenuated after accounting for differences in sociodemographic factors. However, racial/ethnic differences in depression and anxiety were no longer significant after accounting for greater prior trauma exposure and childhood emotional abuse in White participants. CONCLUSIONS: The present findings suggest prior differences in previous trauma exposure partially mediate the observed racial/ethnic differences in posttraumatic depression and anxiety symptoms following a recent trauma. Our findings further demonstrate that racial/ethnic groups show similar rates of symptom recovery over time. Future work utilizing longer time-scale data is needed to elucidate potential racial/ethnic differences in long-term symptom trajectories.

Genome-wide association study of positive emotion identifies a genetic variant and a role for microRNAs.

Positive affect denotes a state of pleasurable engagement with the environment eliciting positive emotion such as contentment, enthusiasm or happiness. Positive affect is associated with favorable psychological, physical and economic outcomes in many longitudinal studies. With a heritability of ⩽64%, positive affect is substantially influenced by genetic factors; however, our understanding of genetic pathways underlying individual differences in positive affect is still limited. Here, through a genome-wide association study of positive affect in African-American participants, we identify a single-nucleotide polymorphism, rs322931, significantly associated with positive affect at P<5 × 10-8, and replicate this association in another cohort. Furthermore, we show that the minor allele of rs322931 predicts expression of microRNAs miR-181a and miR-181b in human brain and blood, greater nucleus accumbens reactivity to positive emotional stimuli and enhanced fear inhibition. Prior studies have suggested that miR-181a is part of the reward neurocircuitry. Taken together, we identify a novel genetic variant for further elucidation of genetic underpinning of positive affect that mediates positive emotionality potentially via the nucleus accumbens and miR-181.

Self-association of organic solutes in solution: a NEXAFS study of aqueous imidazole.

N K-edge near-edge X-ray absorption fine-structure (NEXAFS) spectra of imidazole in concentrated aqueous solutions have been acquired. The NEXAFS spectra of the solution species differ significantly from those of imidazole monomers in the gas phase and in the solid state of imidazole, demonstrating the strong sensitivity of NEXAFS to the local chemical and structural environment. In a concentration range from 0.5 to 8.2 mol L(-1) the NEXAFS spectrum of aqueous imidazole does not change strongly, confirming previous suggestions that imidazole self-associates are already present at concentrations more dilute than the range investigated here. We show that various types of electronic structure calculations (Gaussian, StoBe, CASTEP) provide a consistent and complete interpretation of all features in the gas phase and solid state spectra based on ground state electronic structure. This suggests that such computational modelling of experimental NEXAFS will permit an incisive analysis of the molecular interactions of organic solutes in solutions. It is confirmed that microhydrated clusters with a single imidazole molecule are poor models of imidazole in aqueous solution. Our analysis indicates that models including both a hydrogen-bonded network of hydrate molecules, and imidazole-imidazole interactions, are necessary to explain the electronic structure evident in the NEXAFS spectra.

Development and validation of a brief screener for posttraumatic stress disorder risk in emergency medical settings.

OBJECTIVE: Predicting risk of posttraumatic stress disorder (PTSD) in the acute care setting is challenging given the pace and acute care demands in the emergency department (ED) and the infeasibility of using time-consuming assessments. Currently, no accurate brief screening for long-term PTSD risk is routinely used in the ED. One instrument widely used in the ED is the 27-item Immediate Stress Reaction Checklist (ISRC). The aim of this study was to develop a short screener using a machine learning approach and to investigate whether accurate PTSD prediction in the ED can be achieved with substantially fewer items than the IRSC. METHOD: This prospective longitudinal cohort study examined the development and validation of a brief screening instrument in two independent samples, a model development sample (N = 253) and an external validation sample (N = 93). We used a feature selection algorithm to identify a minimal subset of features of the ISRC and tested this subset in a predictive model to investigate if we can accurately predict long-term PTSD outcomes. RESULTS: We were able to identify a reduced subset of 5 highly predictive features of the ISRC in the model development sample (AUC = 0.80), and we were able to validate those findings in the external validation sample (AUC = 0.84) to discriminate non-remitting vs. resilient trajectories. CONCLUSION: This study developed and validated a brief 5-item screener in the ED setting, which may help to improve the diagnostic process of PTSD in the acute care setting and help ED clinicians plan follow-up care when patients are still in contact with the healthcare system. This could reduce the burden on patients and decrease the risk of chronic PTSD.

Childhood adversities and risk of posttraumatic stress disorder and major depression following a motor vehicle collision in adulthood.

AIMS: Childhood adversities (CAs) predict heightened risks of posttraumatic stress disorder (PTSD) and major depressive episode (MDE) among people exposed to adult traumatic events. Identifying which CAs put individuals at greatest risk for these adverse posttraumatic neuropsychiatric sequelae (APNS) is important for targeting prevention interventions. METHODS: Data came from n = 999 patients ages 18-75 presenting to 29 U.S. emergency departments after a motor vehicle collision (MVC) and followed for 3 months, the amount of time traditionally used to define chronic PTSD, in the Advancing Understanding of Recovery After Trauma (AURORA) study. Six CA types were self-reported at baseline: physical abuse, sexual abuse, emotional abuse, physical neglect, emotional neglect and bullying. Both dichotomous measures of ever experiencing each CA type and numeric measures of exposure frequency were included in the analysis. Risk ratios (RRs) of these CA measures as well as complex interactions among these measures were examined as predictors of APNS 3 months post-MVC. APNS was defined as meeting self-reported criteria for either PTSD based on the PTSD Checklist for DSM-5 and/or MDE based on the PROMIS Depression Short-Form 8b. We controlled for pre-MVC lifetime histories of PTSD and MDE. We also examined mediating effects through peritraumatic symptoms assessed in the emergency department and PTSD and MDE assessed in 2-week and 8-week follow-up surveys. Analyses were carried out with robust Poisson regression models. RESULTS: Most participants (90.9%) reported at least rarely having experienced some CA. Ever experiencing each CA other than emotional neglect was univariably associated with 3-month APNS (RRs = 1.31-1.60). Each CA frequency was also univariably associated with 3-month APNS (RRs = 1.65-2.45). In multivariable models, joint associations of CAs with 3-month APNS were additive, with frequency of emotional abuse (RR = 2.03; 95% CI = 1.43-2.87) and bullying (RR = 1.44; 95% CI = 0.99-2.10) being the strongest predictors. Control variable analyses found that these associations were largely explained by pre-MVC histories of PTSD and MDE. CONCLUSIONS: Although individuals who experience frequent emotional abuse and bullying in childhood have a heightened risk of experiencing APNS after an adult MVC, these associations are largely mediated by prior histories of PTSD and MDE.

Community Violence Exposure is Associated with Hippocampus-Insula Resting State Functional Connectivity in Urban Youth.

Our previous work has linked childhood violence exposure in Black youth to functional changes in the hippocampus, a brain region sensitive to stress. However, different contexts of violence exposure (e.g., community, home, school) may have differential effects on circuitry. We investigated the unique effect of community violence in predicting resting-state functional connectivity (rsFC) in the hippocampus. Fifty-two (26F) violence-exposed Black youth ages 8-15 performed resting-state functional neuroimaging scans while looking at a fixation cross for seven minutes with eyes open. Seed-based analyses were conducted to examine the association between total violence exposure and rsFC of the hippocampus to the whole brain. Follow-up hierarchical regression analysis were performed to specifically investigate community violence. Violence exposure was associated with higher hippocampus rsFC with a core node of the Default Mode Network (i.e., posterior cingulate cortex) and lower hippocampal rsFC with a core node of the Salience Network (i.e., insula). Community violence uniquely associated with lower hippocampus-insula rsFC, after controlling for home and school violence, sex and age. Age-related decreases in hippocampus-insula rsFC were also present in youth with lower violence exposure, but not in youth with higher violence exposure. This is one of the first studies to investigate the unique impact of community violence, above home and school violence, on threat circuitry. Our data suggest functional alterations in the hippocampus in violence-exposed youth, and that violence in the community may be a more salient form of threat exposure compared to other forms of violence experienced by youth.

Diabetic ketoacidosis and mortality in COVID-19 infection.

AIM: - Patients with diabetes have increased morbidity and mortality from COVID-19. Case reports describe patients with simultaneous COVID-19 and diabetic acidosis (DKA), however there is limited data on the prevalence, predictors and outcomes of DKA in these patients. METHODS: - Patients with COVID-19 were identified from the electronic medical record. DKA was defined by standardized criteria. Proportional hazard regression models were used to determine risk factors for, and mortality from DKA in COVID-19. RESULTS: - Of 2366 patients admitted for COVID-19, 157 (6.6%) patients developed DKA, 94% of whom had antecedent type 2 diabetes, 0.6% had antecedent type 1 diabetes, and 5.7% patients had no prior diagnosis of diabetes. Patients with DKA had increased hospital length of stay and in-patient mortality. Higher HbA1c predicted increased risk of incident DKA (HR 1.47 per 1% increase, 95% CI 1.40-1.54). Risk factors for mortality included older age (HR 1.07 per 5 years, 95% CI 1.06-1.08) and need for pressors (HR 2.33, 95% CI 1.82-2.98). Glucocorticoid use was protective in patients with and without DKA. CONCLUSION: - The combination of DKA and COVID-19 is associated with greater mortality, driven by older age and COVID-19 severity.

Identification of a calcitonin-like diuretic hormone that functions as an intrinsic modulator of the American lobster, Homarus americanus, cardiac neuromuscular system.

In insects, a family of peptides with sequence homology to the vertebrate calcitonins has been implicated in the control of diuresis, a process that includes mixing of the hemolymph. Here, we show that a member of the insect calcitonin-like diuretic hormone (CLDH) family is present in the American lobster, Homarus americanus, serving, at least in part, as a powerful modulator of cardiac output. Specifically, during an ongoing EST project, a transcript encoding a putative H. americanus CLDH precursor was identified; a full-length cDNA was subsequently cloned. In silico analyses of the deduced prepro-hormone predicted the mature structure of the encoded CLDH to be GLDLGLGRGFSGSQAAKHLMGLAAANFAGGPamide (Homam-CLDH), which is identical to a known Tribolium castaneum peptide. RT-PCR tissue profiling suggests that Homam-CLDH is broadly distributed within the lobster nervous system, including the cardiac ganglion (CG), which controls the movement of the neurogenic heart. RT-PCR analysis conducted on pacemaker neuron- and motor neuron-specific cDNAs suggests that the motor neurons are the source of the CLDH message in the CG. Perfusion of Homam-CLDH through the isolated lobster heart produced dose-dependent increases in both contraction frequency and amplitude and a dose-dependent decrease in contraction duration, with threshold concentrations for all parameters in the range 10(-11) to 10(-10) mol l(-1) or less, among the lowest for any peptide on this system. This report is the first documentation of a decapod CLDH, the first demonstration of CLDH bioactivity outside the Insecta, and the first detection of an intrinsic neuropeptide transcript in the crustacean CG.

The peptide hormone pQDLDHVFLRFamide (crustacean myosuppressin) modulates the Homarus americanus cardiac neuromuscular system at multiple sites.

pQDLDHVFLRFamide is a highly conserved crustacean neuropeptide with a structure that places it within the myosuppressin subfamily of the FMRFamide-like peptides. Despite its apparent ubiquitous conservation in decapod crustaceans, the paracrine and/or endocrine roles played by pQDLDHVFLRFamide remain largely unknown. We have examined the actions of this peptide on the cardiac neuromuscular system of the American lobster Homarus americanus using four preparations: the intact animal, the heart in vitro, the isolated cardiac ganglion (CG), and a stimulated heart muscle preparation. In the intact animal, injection of myosuppressin caused a decrease in heartbeat frequency. Perfusion of the in vitro heart with pQDLDHVFLRFamide elicited a decrease in the frequency and an increase in the amplitude of heart contractions. In the isolated CG, myosuppressin induced a hyperpolarization of the resting membrane potential of cardiac motor neurons and a decrease in the cycle frequency of their bursting. In the stimulated heart muscle preparation, pQDLDHVFLRFamide increased the amplitude of the induced contractions, suggesting that myosuppressin modulates not only the CG, but also peripheral sites. For at least the in vitro heart and the isolated CG, the effects of myosuppressin were dose-dependent (10(-9) to 10(-6) mol l(-1) tested), with threshold concentrations (10(-8)-10(-7) mol l(-1)) consistent with the peptide serving as a circulating hormone. Although cycle frequency, a parameter directly determined by the CG, consistently decreased when pQDLDHVFLRFamide was applied to all preparation types, the magnitudes of this decrease differed, suggesting the possibility that, because myosuppressin modulates the CG and the periphery, it also alters peripheral feedback to the CG.

Extraction of a melanoma growth-stimulatory activity from culture medium conditioned by the Hs0294 human melanoma cell line.

Extracts of conditioned medium (CM) from Hs0294 human malignant melanoma cells stimulate [3H]thymidine incorporation and an increase in cell number in serum-depleted Hs0294 cells. This activity is acid and heat stable, nonproteolytic, protease sensitive, contains disulfide bonds and elutes broadly from a Bio-Gel P-30 column with an approximate molecular weight range of 6,000 to 25,000. Hs0294 CM also stimulates [3H]thymidine incorporation in nonmalignant human nevus cells and normal rat kidney fibroblast cells but not in human fibroblasts. There was only limited competition with 125I-epidermal growth factor in binding assays. Hs0294 CM extracts stimulate anchorage-independent growth in normal rat kidney fibroblast cells in soft agar but not in Hs0294 cells, nevus cells, or human fibroblasts. This second activity elutes from the Bio-Gel P-30 column in two positions with apparent molecular weights of 27,000 and 11,000.

In vitro growth promotion in human malignant melanoma cells by fibroblast growth factor.

Bovine pituitary fibroblast growth factor (FGF) stimulates the incorporation of [3H]thymidine into DNA in serum-depleted cultures of some but not other human melanoma cells. The melanotic malignant melanoma cell line MIRW exhibited a 40% increase in [3H]thymidine incorporation into DNA and a 48% increase in cell number in response to 3.73 x 10(-9) M FGF. This same concentration of FGF produced a 22% increase in [3H]thymidine incorporation in the melanotic melanoma cell line Hs0294. However, FGF had no effect on the amelanotic melanoma cell line Hs0675, early-passage cultures of a human amelanotic melanoma (W-1), or early-passage cultures of a congenital nevus (N-1).

Genome-wide gene-based analysis suggests an association between Neuroligin 1 (NLGN1) and post-traumatic stress disorder.

Post-traumatic stress disorder (PTSD) develops in only some people following trauma exposure, but the mechanisms differentially explaining risk versus resilience remain largely unknown. PTSD is heritable but candidate gene studies and genome-wide association studies (GWAS) have identified only a modest number of genes that reliably contribute to PTSD. New gene-based methods may help identify additional genes that increase risk for PTSD development or severity. We applied gene-based testing to GWAS data from the Grady Trauma Project (GTP), a primarily African American cohort, and identified two genes (NLGN1 and ZNRD1-AS1) that associate with PTSD after multiple test correction. Although the top SNP from NLGN1 did not replicate, we observed gene-based replication of NLGN1 with PTSD in the Drakenstein Child Health Study (DCHS) cohort from Cape Town. NLGN1 has previously been associated with autism, and it encodes neuroligin 1, a protein involved in synaptogenesis, learning, and memory. Within the GTP dataset, a single nucleotide polymorphism (SNP), rs6779753, underlying the gene-based association, associated with the intermediate phenotypes of higher startle response and greater functional magnetic resonance imaging activation of the amygdala, orbitofrontal cortex, right thalamus and right fusiform gyrus in response to fearful faces. These findings support a contribution of the NLGN1 gene pathway to the neurobiological underpinnings of PTSD.

Persistent left superior vena cava demonstrated by radionuclide angiocardiography: case report.

This report presents a patient with a persistent left superior vena cava demonstrated by radionuclide angiocardiography. The appearance is characteristic.

Residual spleen found on denatured red blood cell scan following negative colloid scans.

The technetium-sulfur colloid liver-spleen examination is widely used to evaluate patients with idiopathic thrombocytopenic purpura for residual splenic tissue following splenectomy. Technetium-labeled heat-damaged red blood cell imaging is another sensitive test for residual splenic tissue. We recently encountered a patient with idiopathic thrombocytopenic purpura who was initially evaluated with a technetium sulfur colloid scan which was negative. A denatured red blood cell scan was subsequently performed which revealed intense focal activity in the region of the splenic bed. Surgery confirmed this to be splenic tissue. Our results emphasize the utility of the denatured red blood cell examination in the setting of strong clinical suspicion for residual splenic tissue following a negative sulfur colloid study.

Abnormal radionuclide angiogram in cervical lymphadenitis: case report.

We have observed increased activity over the neck on radionuclide angiograms of two patients with cervical lymphadenitis. This incidental findings should not be confused with other causes of locally increased perfusion.

Technetium pertechnetate scintigraphy in an ileal duplication of the stomach and duodenum.

We report a patient with ileal duplication of the stomach and duodenum that presented with gastrointestinal bleeding. The scan appearance of the duplicated stomach in both shape and temporal course of activity bore a striking resemblance to the patient's homotopic stomach.

Control-related cognitions and depression among inpatient children and adolescents.

In previous studies, children with numerous depressive symptoms have shown two patterns of control-related cognition: (1) low levels of perceived personal competence, and (2) "contingency uncertainty"--confusion regarding the causes of significant events. The generality of these findings was tested for more seriously disturbed children. Three child inpatient samples, from separate psychiatric hospitals, completed the Children's Depression Inventory (CDI) plus measures of control-related beliefs. In all three samples, the findings resembled those of previous studies: CDI scores were significantly related to low perceived competence and to contingency uncertainty; by contrast, CDI scores were only weakly related to perceived noncontingency. The findings suggest that depressive symptoms in children may be (1) more closely linked to "personal helplessness" than to "universal helplessness," and (2) more closely linked to uncertainty about the causes of events than to firm beliefs in noncontingency. The findings carry implications for etiology and treatment of child depression.

Usefulness of preoperative lymphoscintigraphy for the identification of sentinel lymph nodes in melanoma.

BACKGROUND: The exact role of lymphoscintigraphy (LS) in the evaluation of sentinel lymph nodes (SLNs) in melanoma is controversial. METHODS: We reviewed our experience with preoperative LS for the determination of the lymph node drainage pattern of clinically node negative primary melanomas, with attention to the rate of ambiguous drainage and the effect of previous wide local excision (WLE). RESULTS: The scans of 87 patients who underwent LS at our institution for evaluation of their primary melanomas from 1995 to the present were reviewed. Fourteen of the primary tumor sites were in the head and neck region, 41 were truncal, and 32 were in the extremities. The average tumor thickness was 2.6 mm. Nine of 14 (64%) head/neck lesions and 12 of 41 (29%) truncal lesions displayed ambiguous drainage, as compared with only 2 of 32 (6%) extremity lesions (P <0.05). Forty-one of the 87 patients (47%) had undergone previous WLE of their primary lesion prior to their LS. The number of draining basins for the WLE and the non-WLE groups were not significantly different, and at least one SLN was found for all WLE cases. CONCLUSIONS: Preoperative LS is important for the treatment planning of SLN biopsy for head/neck and truncal melanomas, but adds little additional information for extremity lesions. Lymph node drainage scans and subsequent SLN biopsies are not contraindicated in the presence of a prior WLE.

Gastric activity on dipyridamole 201Tl myocardial perfusion imaging: a clinically useful finding.

To determine the potential association of increased 201Tl uptake by the stomach with symptoms referable to gastritis, 39 consecutive patients experiencing chest pain syndromes underwent a routine dipyridamole 201Tl pharmacological stress test. With the patient in a fasting state, dipyridamole was infused intravenously (0.56 mg kg-1), shortly followed by 201Tl infusion and subsequent image acquisition for single photon emission tomography (SPET). The original 32 SPET images over 180 degrees of arc were interpreted without knowledge of clinical data, using a 4-point scoring system. Patients with active symptoms of gastro-oesophageal discomfort (n = 17) were found to have significantly greater 201Tl stomach uptake scores, compared to the little or no uptake in the 22 patients without such active symptoms (P = 0.0001). A stepwise logistic regression analysis was used to determine which factor(s) showed independent predictive value of 201Tl gastric uptake. The only two independent variables identified were the presence of active gastritis symptoms and the use of anti-gastritis medications. Elevated gastric 201Tl uptake may be a clinically useful finding indicative of gastric inflammation that may be of value in the differential diagnosis of chest and epigastric discomfort.

Denial of emergency department authorization of potentially high-risk patients by managed care.

This study was designed to evaluate patients presenting to a large urban university emergency department (ED) who were subsequently denied authorization for reimbursed care by their managed care provider and to characterize the denial as potentially safe or unsafe based on published triage criteria. A consecutive case surveillance was performed from October 1, 1994 to September 30, 1995 at a university-based ED (30,000 visits per year) for adult patients in inner-city Chicago. Cases were comprised of adult managed care participants whose providers refused by telephone to authorize payment for ED services and who then left the ED without treatment. Chief complaints and vital signs were used to categorize patients as high-risk or nonemergent based on previously published criteria. A total of 2,965 adult managed care patients presented to the ED during the study period, representing 11.1% of the total ED census. Of these patients, 244 (8.2%) were denied authorization for payment of their care. By previously established criteria, 115 (47.1%) were identified as potentially unstable, 61 (53%) due to abnormal vital signs and 54 (47%) with other high-risk indications such as severe pain, chest pain, or abdominal pain. These potentially high-risk patients may subsequently suffer adverse outcomes. Current guidelines used for telephone triage by managed care to divert patients from our ED do not meet previously published safe triage criteria.