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OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked with menopause symptoms (eg, vasomotor, urinary) and their sequelae (eg, sexual difficulties). However, PTSD is a heterogeneous disorder, and less is known about which aspects may be most associated with menopause-related health. METHODS: Using confirmatory factor analyses, we evaluated five structural models of PTSD symptoms in 208 predominately postmenopausal women veterans (aged 45-64 years). We investigated associations between PTSD-operationalized as a probable diagnosis and symptom dimensions of the best-fitting model-and common menopause-related health concerns, including (1) vasomotor, urinary, and vaginal symptoms; (2) vasomotor symptom interference; and (3) sexual functioning. RESULTS: A six-factor anhedonia model-comprising re-experiencing, avoidance, negative affect, anhedonia, anxious arousal, and dysphoric arousal-provided optimal fit. Both probable PTSD and greater symptoms across all dimensions were linked with presence of urinary and vasomotor, but not vaginal, symptoms. Comparing dimensions revealed that negative affect and dysphoric arousal were particularly associated with urinary symptoms, whereas dysphoric arousal was the factor most strongly related to vasomotor symptom interference. Associations between PTSD and sexual dysfunction were mixed; whereas there was no relation with probable diagnosis, all dimensions were linked with adverse sexual sequelae. CONCLUSIONS: PTSD-considered categorically and dimensionally-was relevant to menopause-related health in midlife women veterans. Further, symptoms of negative affect and dysphoric arousal were particularly related to urinary and vasomotor symptoms. These specific symptoms may drive associations between PTSD and these aspects of menopause-related health. Clinical interventions targeting these symptoms may promote midlife women's health.
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BACKGROUND: Discrimination is an important social determinant of perinatal depression; however, evidence is limited regarding modifiable social and psychological factors that may moderate this association. We examined whether social support and resilience could protect against the adverse effects of discrimination on perinatal depressive symptoms. METHODS: Pregnant people (N = 589) receiving Expect With Me group prenatal care in Nashville, TN and Detroit, MI completed surveys during third trimester of pregnancy and six months postpartum. Linear regression models tested the association between discrimination and depressive symptoms, and the moderating effects of social support and resilience, during pregnancy and postpartum. RESULTS: The sample was predominantly Black (60.6 %), Hispanic (15.8 %) and publicly insured (71 %). In multivariable analyses, discrimination was positively associated with depressive symptoms during pregnancy (B = 4.44, SE = 0.37, p ≤0.001) and postpartum (B = 3.78, SE = 0.36, p < 0.001). Higher social support and resilience were associated with less depressive symptoms during pregnancy (B = -0.49, SE = 0.08, p < 0.001 and B = -0.67, SE = 0.10, p < 0.001, respectively) and postpartum (B = -0.32, SE = 0.07, p < 0.001 and B = -0.56, SE = 0.08, p < 0.001, respectively). Social support was protective against discrimination (pregnancy interaction B = -0.23, SE = 0.09, p = 0.011; postpartum interaction B = -0.35, SE = 0.07, p < 0.001). There was no interaction between discrimination and resilience at either time. LIMITATIONS: The study relied on self-reported measures and only included pregnant people who received group prenatal care in two urban regions, limiting generalizability. CONCLUSIONS: Social support and resilience may protect against perinatal depressive symptoms. Social support may also buffer the adverse effects of discrimination on perinatal depressive symptoms, particularly during the postpartum period.
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Depresión Posparto , Resiliencia Psicológica , Embarazo , Femenino , Humanos , Depresión/psicología , Periodo Posparto/psicología , Apoyo Social , Atención Prenatal , Depresión Posparto/diagnóstico , Depresión Posparto/epidemiología , Depresión Posparto/prevención & controlRESUMEN
BACKGROUND Nephro-colic fistulas are uncommon, generally caused by local inflammation, trauma, or neoplasia affecting the kidney or the colon. Their association with a coralliform stone is described in a few case reports, but their management is difficult and differs quite a lot, depending on the clinical situation. We report an atypical clinical case of a reno-colic fistula associated with a staghorn calculus. This case adds to the literature an iconography rarely found. CASE REPORT A 68-year-old woman presented to the Emergency Department with respiratory symptoms and chronic abdominal pain. The biological results showed a high inflammatory syndrome. The radiological assessment revealed a retroperitoneal and left retro-renal abscess, attributed to a left nephro-colic fistula associated with the partial passage of a lithiasis within the colonic lumen. Colonoscopy confirmed the diagnosis. Multiple recurrences of diverticulitis in this region could be the origin of the complication. First, the patient was treated with antibiotic therapy and radiological drainage. Second, she benefited from a left nephrectomy, left segmental colectomy, and splenectomy. The clinical and radiological evolution were favorable after surgery. The follow-up was disrupted by hospitalizations in the Cardiology Department for cardiac decompensation. CONCLUSIONS Kidney stones along with local inflammatory phenomena can be the cause of a nephro-colic fistula. Due to the lack of guidelines in such cases, their diagnosis and management are difficult to ascertain. Surgery is the right course of treatment.
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Absceso Abdominal , Cólico , Fístula Intestinal , Cálculos Renales , Cálculos Coraliformes , Femenino , Humanos , Anciano , Cálculos Coraliformes/complicaciones , Cólico/complicaciones , Absceso/complicaciones , Absceso Abdominal/diagnóstico por imagen , Absceso Abdominal/etiología , Fístula Intestinal/diagnóstico por imagen , Fístula Intestinal/etiología , Fístula Intestinal/cirugíaRESUMEN
The ongoing Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic has highlighted the threat that viral outbreaks pose to global health. A key tool in the arsenal to prevent and control viral disease outbreaks is disinfection of equipment and surfaces with formulations that contain virucidal agents (VA). However, assessment of the efficacy of virus inactivation often requires live virus assays or surrogate viruses such as Modified Vaccinia Virus Ankara (MVA), which can be expensive, time consuming and technically challenging. Therefore, we have developed a pseudo-typed virus (PV) based approach to assess the inactivation of enveloped viruses with a fast and quantitative output that can be adapted to emerging viruses. Additionally, we have developed a method to completely remove the cytotoxicity of virucidal agents while retaining the required sensitivity to measure PV infectivity. Our results indicated that the removal of cytotoxicity was an essential step to accurately measure virus inactivation. Further, we demonstrated that there was no difference in susceptibility to virus inactivation between PVs that express the envelopes of HIV-1, SARS-CoV-2, and Influenza A/Indonesia. Therefore, we have developed an effective and safe alternative to live virus assays that enables the rapid assessment of virucidal activity for the development and optimization of virucidal reagents.
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Gripe Humana , Virosis , Virus , Humanos , Desinfección/métodos , ViriónRESUMEN
STUDY OBJECTIVE: Airway management is a crucial part of out-of-hospital care. It is not known if the rate of overall agency intubation attempts is associated with intubation success. We sought to evaluate the association between agency intubation attempt rate and intubation success using a national out-of-hospital database. METHODS: We conducted a retrospective secondary analysis of the ESO Data Collaborative from 2018 to 2019, and included all adult cases with an endotracheal intubation attempt. We calculated the number of intubations attempted per 100 responses, advanced life support responses, and transports for each agency. We excluded cases originating at health care facilities and outliers. We used multivariable logistic regression to evaluate the association between agency intubation attempt rate and 1) intubation success and 2) first-pass success. We adjusted for confounders. RESULTS: We included 1,005 agencies attempting 58,509 intubations. Overall, the intubation success rate was 78.8%, and the first-pass success rate was 68.5%. Per agency, the median rate of intubation attempts per 100 emergency medical service responses was 0.8 (interquartile range 0.6 to 1.1). Rates of intubation attempts per 100 responses (adjusted odds ratio [aOR] 1.7; 95% confidence interval [CI] 1.6 to 1.8), advanced life support responses (aOR 1.18; 95% CI 1.16 to 1.20), and transports (aOR 1.21; 95% CI 1.18 to 1.22) were all associated with intubation success. These relationships were similar for first-pass success but with smaller effect sizes. CONCLUSION: Higher agency rates of intubation attempts were associated with increased rates of intubation success and first-pass success.
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Servicios Médicos de Urgencia , Intubación Intratraqueal , Humanos , Intubación Intratraqueal/estadística & datos numéricos , Intubación Intratraqueal/métodos , Estudios Retrospectivos , Femenino , Masculino , Servicios Médicos de Urgencia/estadística & datos numéricos , Persona de Mediana Edad , Adulto , Anciano , Manejo de la Vía Aérea/métodos , Manejo de la Vía Aérea/estadística & datos numéricos , Estados Unidos , Modelos LogísticosRESUMEN
Fixed-timed artificial insemination (FTAI) protocols for beef cattle in South America are primarily based on estradiol esters and intravaginal progesterone-releasing devices (IVPD). The objective of this study was to determine the optimal gonadotropin-releasing hormone (GnRH)-based protocol as an alternative to the use of estrogen-based protocols in grazing Bos taurus suckling beef cows. All cows received an IVPD on the day of protocol initiation and prostaglandin F2α (PG) plus equine chorionic gonadotropin (eCG) treatments at the time of IVPD removal. In Experiment 1, cows (n = 235) were randomly assigned to one of four treatments: (i) 7-day estradiol = 2 mg of estradiol benzoate (EB) at IVPD insertion on Day 9 and 1 mg of estradiol cypionate (ECP) at IVPD removal on Day 2; (ii) 7-day GnRH = 10 µg of GnRH at IVPD insertion on Day 10, IVPD removal on Day 3 and GnRH at FTAI; (iii) 7 & 7 estradiol = PG at IVPD insertion on Day 16, EB on Day 9 and ECP at IVPD removal on Day 2; (iv) 7 & 7 GnRH = PG at IVPD insertion on Day 17, GnRH on Day 10, IVPD removal on Day 3 and GnRH at FTAI. In Experiment 2, cows (n = 462) were randomly assigned to one of four treatments: (i) 6-day estradiol = EB at IVPD insertion on Day 9, IVPD removal on Day 3 and GnRH at FTAI; (ii) 7-day estradiol; (iii) 7-day GnRH; (iv) 7 & 7 GnRH. In Experiment 1, plasma progesterone concentrations and percentage of cows with a corpus luteum (CL) at IVPD removal, and pregnancy per AI (P/AI) were greater for cows subjected to GnRH-based protocols compared with cows subjected to estrogen-based protocols (p < 0.01). In Experiment 2, cows subjected to the 7 & 7 GnRH protocol had the greatest P/AI (p < 0.01). In summary, GnRH-based FTAI protocols resulted in similar or greater P/AI compared to estrogen-based FTAI protocols in grazing postpartum Bos taurus suckled beef cows. The greatest P/AI was attained with the 7 & 7 GnRH protocol.
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The ongoing SARS-CoV-2 pandemic was initially managed by non-pharmaceutical interventions such as diagnostic testing, isolation of positive cases, physical distancing and lockdowns. The advent of vaccines has provided crucial protection against SARS-CoV-2. Neutralising antibody (nAb) responses are a key correlate of protection, and therefore measuring nAb responses is essential for monitoring vaccine efficacy. Fingerstick dried blood spots (DBS) are ideal for use in large-scale sero-surveillance because they are inexpensive, offer the option of self-collection and can be transported and stored at ambient temperatures. Such advantages also make DBS appealing to use in resource-limited settings and in potential future pandemics. In this study, nAb responses in sera, venous blood and fingerstick blood stored on filter paper were measured. Samples were collected from SARS-CoV-2 acutely infected individuals, SARS-CoV-2 convalescent individuals and SARS-CoV-2 vaccinated individuals. Good agreement was observed between the nAb responses measured in eluted DBS and paired sera. Stability of nAb responses was also observed in sera stored on filter paper at room temperature for 28 days. Overall, this study provides support for the use of filter paper as a viable sample collection method to study nAb responses.
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COVID-19 , SARS-CoV-2 , Humanos , Control de Enfermedades Transmisibles , Anticuerpos Neutralizantes , Transporte BiológicoRESUMEN
Human immunodeficiency virus type 1 (HIV-1) is able to infect a variety of cell types with differences in entry efficiency and replication kinetics determined by the host cell type or the viral phenotype. The phenotype of the virus produced from these various cell types, including infectivity, co-receptor usage and neutralisation sensitivity, may also be affected by the characteristics of the producing cell. This can be due to incorporation of variant cell-specific molecules or differences in post-translational modifications of the gp41/120 envelope. In this study we produced genetically identical virus strains from macrophages, CD4-enriched lymphocytes as well as Th1 and Th2 CD4+ cell lines and compared each different virus stock for their infectivity in various cell types and sensitivity to neutralisation. In order to study the effect of the producer host cell on the virus phenotype, virus stocks were normalised on infectivity and were sequenced to confirm env gene homogeneity. Virus production by Th1 or Th2 cells did not compromise infectivity of the variant cell types tested. We observed no difference in sensitivity to co-receptor blocking agents upon viral passage through Th1 and Th2 CD4+ cell lineages nor did this affect DC-SIGN-mediated viral capture as measured in a transfer assay to CD4+ lymphocytes. Virus produced by macrophages was comparably sensitive to CC-chemokine inhibition as was virus generated from the array of CD4+ lymphocytes. We identified that virus produced from macrophages was fourteen times more resistant to 2G12 neutralisation than virus produced from CD4+ lymphocytes. Macrophage-produced dual-tropic (R5/X4) virus was six times more efficiently transmitted to CD4+ cells than lymphocyte-derived HIV-1 (p<0.0001) after DCSIGN capture. These results provide further insights to what extent the host cell influences viral phenotype and thereby various aspects of HIV-1 pathogenesis but suggest that viruses generated from Th1 versus Th2 cells are consistent in phenotype.
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VIH-1 , Humanos , VIH-1/fisiología , Linfocitos T CD4-Positivos/metabolismo , Células Th2/metabolismo , Fenotipo , Macrófagos , Polisacáridos/metabolismoRESUMEN
Wild animals are naturally infected with a range of viruses, some of which may be zoonotic. During the human COVID pandemic there was also the possibility of rodents acquiring SARS-CoV-2 from people, so-called reverse zoonoses. To investigate this, we sampled rats (Rattus norvegicus) and mice (Apodemus sylvaticus) from urban environments in 2020 during the human COVID-19 pandemic. We metagenomically sequenced lung and gut tissue and faeces for viruses, PCR screened for SARS-CoV-2, and serologically surveyed for anti-SARS-CoV-2 Spike antibodies. We describe the range of viruses that we found in these two rodent species. We found no molecular evidence of SARS-CoV-2 infection, though in rats we found lung antibody responses and evidence of neutralization ability that are consistent with rats being exposed to SARS-CoV-2 and/or exposed to other viruses that result in cross-reactive antibodies.
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COVID-19 , Virus , Humanos , Animales , Ratas , Ratones , SARS-CoV-2 , Roedores , Pandemias , Anticuerpos AntiviralesRESUMEN
The SARS-CoV-2 pandemic enables the analysis of immune responses induced against a novel coronavirus infecting immunologically naïve individuals. This provides an opportunity for analysis of immune responses and associations with age, sex and disease severity. Here we measured an array of solid-phase binding antibody and viral neutralising Ab (nAb) responses in participants (n=337) of the ISARIC4C cohort and characterised their correlation with peak disease severity during acute infection and early convalescence. Overall, the responses in a Double Antigen Binding Assay (DABA) for antibody to the receptor binding domain (anti-RBD) correlated well with IgM as well as IgG responses against viral spike, S1 and nucleocapsid protein (NP) antigens. DABA reactivity also correlated with nAb. As we and others reported previously, there is greater risk of severe disease and death in older men, whilst the sex ratio was found to be equal within each severity grouping in younger people. In older males with severe disease (mean age 68 years), peak antibody levels were found to be delayed by one to two weeks compared with women, and nAb responses were delayed further. Additionally, we demonstrated that solid-phase binding antibody responses reached higher levels in males as measured via DABA and IgM binding against Spike, NP and S1 antigens. In contrast, this was not observed for nAb responses. When measuring SARS-CoV-2 RNA transcripts (as a surrogate for viral shedding) in nasal swabs at recruitment, we saw no significant differences by sex or disease severity status. However, we have shown higher antibody levels associated with low nasal viral RNA indicating a role of antibody responses in controlling viral replication and shedding in the upper airway. In this study, we have shown discernible differences in the humoral immune responses between males and females and these differences associate with age as well as with resultant disease severity.
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COVID-19 , Masculino , Humanos , Femenino , Anciano , SARS-CoV-2 , Estudios Prospectivos , Formación de Anticuerpos , ARN Viral , Anticuerpos Antivirales , Proteínas de la Nucleocápside , Hospitales , Gravedad del Paciente , Inmunoglobulina MRESUMEN
Limited spatial separation within small islands suggests that observed population divergence may occur due to habitat differences without interruption to gene flow but strong evidence of this is scarce. The wall lizard Teira dugesii lives in starkly contrasting shingle beach and inland habitats on the island of Madeira. We used a matched pairs sampling design to examine morphological and genomic divergence between four beach and adjacent (<1 km) inland areas. Beach populations are significantly darker than corresponding inland populations. Geometric morphometric analyses reveal divergence in head morphology: beach lizards have generally wider snouts. Genotyping-by-sequencing allows the rejection of the hypothesis that beach populations form a distinct lineage. Bayesian analyses provide strong support for models that incorporate gene flow, relative to those that do not, replicated at all pairs of matched sites. Madeiran lizards show morphological divergence between habitats in the face of gene flow, revealing how divergence may originate within small islands.
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Variación Genética , Lagartos , Animales , Flujo Génico , Lagartos/genética , Lagartos/anatomía & histología , Teorema de Bayes , EcosistemaRESUMEN
PURPOSE: Early life adversity (ELA) is associated with sexual risk, but ELA dimensions-and potential mechanisms-have been less examined. We evaluated associations between threat and deprivation-two key ELA dimensions-and sexual behaviors in adolescents. Secondary analyses investigated age at menarche as a mechanism linking ELA with sexual outcomes in girls. We predicted associations between threat and sexual behaviors, with younger age at menarche as a pathway. METHODS: Data were from the National Comorbidity Survey, Adolescent Supplement. Adolescents and caregivers reported on youths' ELA experiences, which were categorized as threat- or deprivation-related. Adolescents reported if they engaged in sex (N = 9,937) and on specific sexual risk indicators, including age at first sex, number of past-year sexual partners, and condom use consistency ("always" vs. "not always" used). Girls reported age at menarche. RESULTS: Threat (odds ratio [OR] = 1.76 [95% confidence interval [CI], 1.62-1.92]) and deprivation (OR = 1.51 [95% CI, 1.24-1.83]) were each linked with engagement in sex, ps<.05. Threat-related experiences were associated with multiple sexual risk markers, even when accounting for deprivation: earlier age at first sex (b = -0.20 [95% CI, -0.27 to 0.13]), greater number of partners (b = 0.17 [95% CI, 0.10-0.25]), and inconsistent condom use (OR = 0.72 [95% CI, 0.64-0.80]), ps <.001. Deprivation was not associated with sexual risk when adjusting for threat. We observed no significant indirect effects through age at menarche. DISCUSSION: Although threat and deprivation were related to engagement in sexual activity, threat-related experiences were uniquely associated with sexual risk. Screening for threat-related ELA may identify adolescents at-risk for poor sexual health.
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Conducta del Adolescente , Conducta Sexual , Femenino , Adolescente , Humanos , Parejas Sexuales , Factores de Riesgo , ComorbilidadRESUMEN
Mycobacterium tuberculosis and human immunodeficiency virus-1 (HIV-1) syndemic interactions are a major global health concern. Despite the clinical significance of coinfection, our understanding of the cellular pathophysiology and the therapeutic pharmacodynamic impact of coinfection is limited. Here, we use single-round infectious HIV-1 pseudotyped viral particles expressing green fluorescent protein alongside M. tuberculosis expressing mCherry to study pathogenesis and treatment. We report that HIV-1 infection inhibited intracellular replication of M. tuberculosis and demonstrate the therapeutic activity of antiviral treatment (efavirenz) and antimicrobial treatment (rifampicin). The described method could be applied for detailed mechanistic studies to inform the development of novel treatment strategies.
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Coinfección , Infecciones por VIH , VIH-1 , Mycobacterium tuberculosis , Tuberculosis , Humanos , Tuberculosis/microbiología , Coinfección/tratamiento farmacológico , Rifampin/uso terapéutico , Infecciones por VIH/tratamiento farmacológicoRESUMEN
Inducible laryngeal obstruction (ILO)/vocal cord dysfunction is frequently encountered in the specialist asthma clinic, where it is often misdiagnosed as asthma or is coexistent with asthma. It causes recurrent distressing episodes of acute dyspnea that can lead to hospital admissions, endotracheal intubation, and fruitless asthma treatment escalation, often including oral glucocorticoids.1-4 Early diagnosis and treatment of ILO offers the prospect of connecting patients with an effective speech- and language-based intervention earlier and avoiding these unnecessary and potentially harmful interventions.
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Obstrucción de las Vías Aéreas , Asma , Enfermedades de la Laringe , Humanos , Pliegues Vocales , Laringoscopía/efectos adversos , Obstrucción de las Vías Aéreas/diagnóstico , Enfermedades de la Laringe/complicaciones , Asma/complicacionesRESUMEN
The scalability of quantum networking will benefit from quantum and classical communications coexisting in shared fibers, the main challenge being spontaneous Raman scattering noise. We investigate the coexistence of multi-channel O-band quantum and C-band classical communications. We characterize multiple narrowband entangled photon pair channels across 1282 nm-1318 nm co-propagating over 48 km of installed standard fiber with record C-band power (>18 dBm) and demonstrate that some quantum-classical wavelength combinations significantly outperform others. We analyze the Raman noise spectrum, optimal wavelength engineering, multi-photon pair emission in entangled photon-classical coexistence, and evaluate the implications for future quantum applications.
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Human immunodeficiency virus type 1 (HIV-1) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have caused two major viral outbreaks during the last century. Two major aspects of HIV-1 and SARS-CoV-2 co-infection have been extensively investigated and deserve attention. First, the impact of the co-infection on the progression of disease caused by HIV-1 or SARS-CoV-2. Second, the impact of the HIV-1 anti-retroviral treatment on SARS-CoV-2 infection. In this review, we aim to summarize and discuss the works produced since the beginning of the SARS-CoV-2 pandemic ranging from clinical studies to in vitro experiments in the context of co-infection and drug development.
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Posttraumatic stress disorder (PTSD) has been increasingly recognized as a potential mental health concern for new mothers. Elevated PTSD symptoms have been associated with maladaptive coping strategies in the postpartum period, a time when women face many challenges, demands, and stressors. However, PTSD symptoms manifest in heterogeneous ways, and focusing only on total symptom scores may obscure more nuanced associations with particular coping styles. In a large, ethnically diverse sample of postpartum women from across the United States (N = 1,315), first we examined associations between total PTSD symptom severity with three distinct coping styles: active-emotional, avoidant-emotional, and problem-focused. In models adjusting for race and educational attainment, total PTSD symptom severity was significantly positively associated with tendencies to use active- and avoidant-emotional, but not problem-focused, coping. We then adopted a novel "symptomics" approach, employing relative importance analyses to examine associations between individual PTSD symptoms with the coping styles. These analyses identified PTSD symptoms that were most strongly associated with each coping style. Notably, whereas several symptoms explained variance in avoidant-emotional coping, only a few symptoms contributed most to active-emotional and problem-focused coping. Moreover, non-specific symptoms of PTSD that are shared with other psychopathology (e.g., difficulty concentrating, loss of interest) explained significant proportions of variance across all coping styles. Collectively, results suggest that a symptomics approach may provide more nuanced insight into how PTSD symptoms are linked to various coping styles in postpartum women, which can help inform potential screening and intervention targets for at-risk women during this period.
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Trastornos por Estrés Postraumático , Adaptación Psicológica , Femenino , Humanos , Salud Mental , Madres , Periodo Posparto , Trastornos por Estrés Postraumático/psicologíaRESUMEN
Urological complaints related to primary hyperparathyroidism are frequently caused by the formation of urolithiasis. We report another rare clinical manifestation of primary hyperparathyroidism associated with urological symptoms. A 68-year-old man presented with dysuria related to benign prostatic hyperplasia. After undergoing endoscopic resection of the prostate, the patient's urinary complaints persisted for several months thereafter. Urinary ultrasound revealed numerous calcifications on the prostatic resection area, requiring a cystoscopy for excision and analysis of the calcifications. This was followed by an endocrine evaluation that revealed a primary hyperparathyroidism due to a single parathyroid adenoma, which was responsible for the prostatic calcifications and the patient's atypical symptomatology. The clinical evolution was favorable after parathyroidectomy. Symptomatic prostatic calcifications, due to primary hyperparathyroidism, on an area of the endoscopic prostate resection are uncommon. The only treatment is endocrine surgery.
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Background: Large variation exists for out-of-hospital-cardiac-arrest (OHCA) prehospital care, but less is known about variations in post-arrest care. We sought to evaluate variation in post-arrest care in Texas as well as factors associated with higher performing hospitals. Methods: We analyzed data in Texas Cardiac Arrest Registry to Enhance Survival (TX-CARES), including all adult, non-traumatic OHCAs from 1/1/2014 through 12/31/ 2020 that survived to hospital admission. We first evaluated variability in provisions of post-arrest care and outcomes. We then stratified hospitals into quartiles based on their rate of survival and evaluated the association between improving quartiles and care. Lastly, we evaluated for outliers in post-arrest care and outcomes using a mixed-effect regression model. Results: We analyzed 7,842 OHCAs admitted to 146 hospitals. We identified large variations in post-arrest care, including targeted temperature management (TTM) (IQR 7.0-51.1%), left heart catheterization (LHC) (IQ 0-25%), and percutaneous coronary intervention (PCI) (IQR 0-10.3%). Higher performing hospital quartiles were associated with higher rates of TTM (aOR 1.42, 95% CI 1.36-1.49), LHC (aOR 2.07, 95% CI 1.92-2.23), and PCI (aOR 2.02, 95% CI 1.81-2.25); but lower rates of bystander CPR (aOR 0.90, 95% CI 0.87-0.94). We identified numerous performance outlier hospitals; 39 for TTM, 34 for PCI, 9 for survival to discharge, and 24 for survival with good neurologic function. Conclusions: Post-arrest care varied widely across Texas hospitals. Hospitals with higher rates of survival to discharge had increased rates of TTM, LHC, and PCI but not bystander CPR.
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Following acute HCV infection, the virus establishes a chronic disease in the majority of patients whilst few individuals clear the infection spontaneously. The precise mechanisms that determine chronic HCV infection or spontaneous clearance are not completely understood but are proposed to be driven by host and viral genetic factors as well as HCV encoded immunomodulatory proteins. Using the HIV-1 LTR as a tool to measure NF-κB activity, we identified that the HCV E1E2 glycoproteins and more so the E2 protein down-modulates HIV-1 LTR activation in 293T, TZM-bl and the more physiologically relevant Huh7 liver derived cell line. We demonstrate this effect is specifically mediated through inhibiting NF-κB binding to the LTR and show that this effect was conserved for all HCV genotypes tested. Transcriptomic analysis of 293T cells expressing the HCV glycoproteins identified E1E2 mediated stimulation of the endoplasmic reticulum (ER) stress response pathway and upregulation of stress response genes such as ATF3. Through shRNA mediated inhibition of ATF3, one of the components, we observed that E1E2 mediated inhibitory effects on HIV-1 LTR activity was alleviated. Our in vitro studies demonstrate that HCV Env glycoprotein activates host ER Stress Pathways known to inhibit NF-κB activity. This has potential implications for understanding HCV induced immune activation as well as oncogenesis.