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Ehrlichia is Gram negative obligate intracellular bacterium that cause human monocytotropic ehrlichiosis (HME). HME is characterized by acute liver damage and inflammation that may progress to fatal toxic shock. We previously showed that fatal ehrlichiosis is due to deleterious activation of inflammasome pathways, which causes excessive inflammation and liver injury. Mammalian cells have developed mechanisms to control oxidative stress via regulation of nuclear factor erythroid 2 related 2 (NRF2) signaling. However, the contribution of NRF2 signaling to Ehrlichia-induced inflammasome activation and liver damage remains elusive. In this study, we investigated the contribution of NRF2 signaling in hepatocytes (HCs) to the pathogenesis of Ehrlichia-induced liver injury following infection with virulent Ixodes ovatus Ehrlichia (IOE, AKA E. japonica). Employing murine model of fatal ehrlichiosis, we found that virulent IOE inhibited NRF2 signaling in liver tissue of infected mice and in HCs as evidenced by downregulation of NRF2 expression, and downstream target GPX4, as well as decreased NRF2 nuclear translocation, a key step in NRF2 activation. This was associated with activation of non-canonical inflammasomes pathway marked by activation of caspase 11, accumulation of reactive oxygen species (ROS), mitochondrial dysfunction, and endoplasmic reticulum (ER) stress. Mechanistically, treatment of IOE-infected HCs with the antioxidant 3H-1,2-Dithiole-3-Thione (D3T), that induces NRF2 activation, attenuated oxidative stress and caspase 11 activation, as well as restored cell viability. Importantly, treatment of IOE-infected mice with D3T resulted in attenuated liver pathology, decreased inflammation, enhanced bacterial clearance, prolonged survival, and resistance to fatal ehrlichiosis. Our study reveals, for the first time, that targeting anti-oxidative signaling pathway is a key approach in the treatment of severe and potential Ehrlichia-induced acute liver injury and sepsis.
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Enfermedad Hepática Crónica Inducida por Sustancias y Drogas , Ehrlichiosis , Ratones , Humanos , Animales , Ehrlichia , Antioxidantes , Factor 2 Relacionado con NF-E2/metabolismo , Inflamasomas , Enfermedad Hepática Crónica Inducida por Sustancias y Drogas/patología , Ehrlichiosis/microbiología , Hígado/patología , Caspasas/metabolismo , Transducción de Señal , Inflamación/patología , Ratones Endogámicos C57BL , MamíferosRESUMEN
A case of Powassan encephalitis occurred in Manitoba, Canada, after the bite of a black-legged tick. Awareness of this emerging tickborne illness is needed because the number of vector tick species is growing. No specific treatment options exist, and cases with illness and death are high. Prevention is crucial.
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Erdheim-Chester disease (ECD) is a rare 'L' (Langerhans) group histiocytic neoplasm that affects a multitude of organ systems, causing osteosclerotic bone lesions, periaortic encasement ('coated' aorta), retroperitoneal fibrosis involving kidneys and ureters ('hairy kidney'), and infiltration of the central nervous system. Cardiovascular involvement can occur in up to 70% of patients and is usually found during computed tomography/magnetic resonance imaging evaluation. When present, cardiovascular symptoms can have wide variability in presentation from asymptomatic to pericarditis, fatal cardiac tamponade, myocardial infarction, conduction abnormalities, heart failure, renal artery stenosis, and claudication. Cardiac involvement found on imaging includes right atrial pseudotumor, right atrioventricular groove infiltration, and pericardial effusions. ECD can involve the large- and medium-sized arteries, often seen as periarterial thickening (commonly coating the aorta) with stenosis/occlusion. Although more cardiovascular ECD cases have begun to be published in the literature, more data are needed on the outcomes of these patients, as well as how cardiovascular manifestations respond to treatment of ECD.
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Enfermedad de Erdheim-Chester , Humanos , Enfermedad de Erdheim-Chester/complicaciones , Enfermedad de Erdheim-Chester/diagnóstico , Enfermedad de Erdheim-Chester/tratamiento farmacológico , Enfermedad de Erdheim-Chester/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Femenino , Anciano , Resultado Fatal , Resultado del TratamientoRESUMEN
BACKGROUND: Atherosclerotic cardiovascular disease is highly prevalent in patients with end-stage kidney disease (ESKD). Kidney transplant (KT) improves patient survival and cardiovascular outcomes. The impact of preexisting coronary artery disease (CAD) and peripheral artery disease (PAD) on posttransplant outcomes remains unclear. METHODS: This is a retrospective study utilizing the United States Renal Data System. Adult diabetic dialysis patients who underwent first KT between 2006 and 2017 were included. The study population was divided into four cohorts based on presence of CAD/PAD: (1) polyvascular disease (CAD + PAD); (2) CAD without PAD; (3) PAD without CAD; (4) no CAD or PAD (reference cohort). The primary outcome was 3-year all-cause mortality. Secondary outcomes were incidence of posttransplant myocardial infarction (MI), cerebrovascular accidents (CVA), and graft failure. RESULTS: The study population included 19,329 patients with 64.4% men, mean age 55.4 years, and median dialysis duration of 2.8 years. Atherosclerotic cardiovascular disease was present in 28% of patients. The median follow up was 3 years. All-cause mortality and incidence of posttransplant MI were higher with CAD and highest in patients with polyvascular disease. The cohort with polyvascular disease had twofold higher all-cause mortality (16.7%, adjusted hazard ratio (aHR) 1.5, p < 0.0001) and a fourfold higher incidence of MI (12.7%, aHR 3.3, p < 0.0001) compared to the reference cohort (8.0% and 3.1%, respectively). There was a higher incidence of posttransplant CVA in the cohort with PAD (3.4%, aHR 1.5, p = 0.01) compared to the reference cohort (2.0%). The cohorts had no difference in graft failure rates. CONCLUSIONS: Preexisting CAD and/or PAD result in worse posttransplant survival and cardiovascular outcomes in patients with diabetes mellitus and ESKD without a reduction in graft survival.
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Enfermedad de la Arteria Coronaria , Diabetes Mellitus , Fallo Renal Crónico , Trasplante de Riñón , Infarto del Miocardio , Enfermedad Arterial Periférica , Accidente Cerebrovascular , Masculino , Humanos , Persona de Mediana Edad , Femenino , Trasplante de Riñón/efectos adversos , Estudios Retrospectivos , Factores de Riesgo , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedad de la Arteria Coronaria/cirugía , Enfermedad de la Arteria Coronaria/complicaciones , Enfermedad Arterial Periférica/diagnóstico , Enfermedad Arterial Periférica/epidemiología , Enfermedad Arterial Periférica/complicaciones , Infarto del Miocardio/epidemiología , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/epidemiología , Fallo Renal Crónico/cirugíaRESUMEN
PURPOSE OF REVIEW: This article aims to illustrate the current state of investigations and management of liver metastases in patients with Neuroendocrine Neoplasms. Neuroendocrine tumours (NETs) are rising in incidence globally and have become the second most prevalent gastrointestinal malignancy in UK and USA. Frequently, patients have metastatic disease at time of presentation. The liver is the most common site of metastases for gastro-enteropancreatic NETs. Characterisation of liver metastases with imaging is important to ensure disease is not under-staged. RECENT FINDINGS: Magnetic resonance imaging and positron emission tomography are now becoming standard of care for imaging liver metastases. There is an increasing armamentarium of therapies available for management of NETs and loco-regional therapy for liver metastases. The data supporting surgical and loco-regional therapy is reviewed with focus on role of liver transplantation. It is important to use appropriate imaging and classification of NET liver metastases. It is key that decisions regarding approach to treatment is undertaken in a multidisciplinary team and that individualised approaches are considered for management of patients with metastatic NETs.
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Objectives:The aim of the study was to examine the incidence, baseline characteristics, and outcomes of Chimeric Antigen Receptor T-cell (CAR-T) therapy admissions in individuals who developed acute respiratory failure (ARF). The study utilized the National Inpatient Sample (NIS) database for the years 2017 to 2020. Methods: The study identified CAR-T cell therapy hospitalizations through the International Classification of Diseases, Tenth Revision, Procedure Coding System (ICD-10-PCS) codes. Patients with acute respiratory failure (ARF) were further classified using specific International Classification of Disease, Tenth Revision, Clinical Modification (ICD-10-CM) codes. Descriptive statistics were performed to analyze baseline characteristics, comorbidities, complications, and outcomes. Results: Analysis of the NIS Database identified 5545 CAR-T therapy admissions between 2017 and 2020, revealing a rising trend over time. In our study, we found that hypertension (39%), dyslipidemia (21.7%), and venous thromboembolism (13%) were the most frequently observed comorbidities in CAR-T cell therapy admissions. Acute respiratory failure (ARF) was reported in 7.1% of admissions, and they had higher all-cause in-hospital mortality than CAR-T cell therapy admissions without ARF (32.9% vs 1.3%, P < 0.001). ARF admissions that required invasive mechanical ventilation (IMV) also had higher all-cause in-hospital mortality compared to admissions not requiring IMV (48.9% vs 11.8%, P = 0.001). There was no difference in the mortality rate among admissions with non-Hodgkin's Lymphoma, Multiple Myeloma, and Leukemia that utilized CAR-T therapy. Conclusions: In this largest study to date, we illuminate the incidence and outcomes of CAR-T cell therapy admissions with ARF. Higher mortality rates were observed in CAR-T cell therapy admissions with ARF. The study emphasizes the crucial role of interdisciplinary collaboration in CAR-T patient management and calls for additional research to clarify ARF's etiology and inform effective management strategies.
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PURPOSE OF REVIEW: Tension-type headache (TTH) continues to be the most prevalent type of headache across all age groups worldwide, and the global burden of migraine and TTH together account for 7% of all-cause years lived with disability (YLDs). TTH has been shown to have a prevalence of up to 80% in several studies and presents a wide range and high variability in clinical settings. The aim of this review is to identify gaps in diagnostics, nosology, and variability in the treatment of children and adolescents who present with headaches without an identifiable etiology. RECENT FINDINGS: Migraine and TTH have been debated to have more similarities than distinctions, increasing chances of misdiagnosis and leading to significant cases diagnosed as probable TTH or probable migraine. The lack of specificity and sensitivity for TTH classification often leads to the diagnosis being made by negating associated migraine symptoms. Although pathology is not well understood, some studies have suggested a neurological basis for TTH, in need of further validation. Some research indicates that nitric oxide signaling plays an integral part in the pain mechanisms related to TTH. Analgesics and non-steroidal anti-inflammatories are usually the first lines of treatment for children with recurring headaches, and additional treatment options include medication and behavioral therapies. With high prevalence and socioeconomic burden among children and adolescents, it's essential to further study Tension-type headaches and secondary headaches without known cause and potential interventions. Treatment studies involving randomized controlled trials are also needed to test the efficacy of various treatments further.
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Trastornos Mentales , Humanos , Niño , Adolescente , Trastornos Mentales/diagnóstico , Cefalea de Tipo Tensional/diagnóstico , Trastornos Migrañosos/diagnóstico , Cefalea/diagnósticoRESUMEN
The objective of this study was to create a new treatment for lung cancer using solid lipid nanoparticles (SLNs) loaded with gemcitabine (GEM) and epigallocatechin-3-gallate (EGCG) that can be administered through the nose. We analyzed the formulation for its effectiveness in terms of micromeritics, drug release, and anti-cancer activity in the benzopyrene-induced Swiss albino mice lung cancer model. We also assessed the pharmacokinetics, biodistribution, biocompatibility, and hemocompatibility of GEM-EGCG SLNs. The GEM-EGCG SLNs had an average particle size of 93.54 ± 11.02 nm, a polydispersity index of 0.146 ± 0.05, and a zeta potential of -34.7 ± 0.4 mV. The entrapment efficiency of GEM and EGCG was 93.39 ± 4.2% and 89.49 ± 5.1%, respectively, with a sustained release profile for both drugs. GEM-EGCG SLNs had better pharmacokinetics than other treatments, and a high drug targeting index value of 17.605 for GEM and 2.118 for EGCG, indicating their effectiveness in targeting the lungs. Blank SLNs showed no pathological lesions in the liver, kidney, and nasal region validating the safety of SLNs. GEM-EGCG SLNs also showed fewer pathological lesions than other treatments and a lower hemolysis rate of 1.62 ± 0.10%. These results suggest that GEM-EGCG SLNs could effectively treat lung cancer.
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Catequina , Desoxicitidina , Gemcitabina , Neoplasias Pulmonares , Nanopartículas , Animales , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacocinética , Desoxicitidina/administración & dosificación , Desoxicitidina/química , Ratones , Catequina/análogos & derivados , Catequina/administración & dosificación , Catequina/farmacocinética , Catequina/química , Nanopartículas/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Distribución Tisular , Administración Intranasal , Tamaño de la Partícula , Liberación de Fármacos , Lípidos/química , Portadores de Fármacos/química , Masculino , LiposomasRESUMEN
ABSTRACT: A Spigelian hernia is an uncommon, atypical protrusion of the peritoneum or abdominal contents via a defect (Spigelian fascia), consisting of the internal oblique aponeuroses and the transversus abdominis. With a frequency ranging from 0.12% to 2% of all abdominal wall hernias, Spigelian hernias are extremely rare. It usually arises from a condition that increases intra-abdominal pressure, the degeneration of the abdominal aponeurotic layers or trauma to the abdominal wall. Herein, we present a case series of patients with varying presentations of Spigelian hernia who presented, who were promptly diagnosed and who were managed successfully with laparoscopic surgical repair.
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Introduction: The prognostic significance of steroid receptors in bladder cancer remains controversial. This study was designed to determine the expression status of androgen receptor (AR), estrogen receptors (ERα and Erß), and its potential role in predicting survival in patients with nonmuscle invasive bladder cancer (NMIBC). Methods: Sixty patients of NMIBC were screened and 57 (41 males and 16 females) were included in our study. The tissue microarray slides were evaluated by pathologists blinded to the clinical information. Association of distribution of steroid receptors with stage, grade, progression, and recurrence was seen. Results: The mean age of the population was 60.9 ± 9.3 years. Pathologically, majority of the patients were Ta (Ta: T1 stage 61.4% vs. 38.6%). Nine (15.8%) of the tumors stained positive for AR while one (1.8%) tumor stained positive for ERα and 36 (63.2%) tumors stained for ERß. A higher proportion of male NMIBC stained positive for AR (19.5% vs. 6.2%, P = 0.420) while ERß positivity was higher in females (58.5% vs. and 75%,P = 0.247). AR-negative tumors showed higher recurrence (20/48%-42%) as compared to AR-positive tumors (2/9%-22%). ERß-positive tumors showed higher recurrence (15/36%-42% vs. 7/21%-33%, P = 0.179). Progression-free survival (PFS) was found to be significantly lower for ERß-negative group (log-rank test P = 0.035). Conclusion: AR and ERß positivity is found in NMIBC patients while ERα shows minimal staining in NMIBC patients. Although it did not reach a statistical significance, a higher proportion of AR-negative and ERß-positive tumors recurred as compared to AR-positive and ERß-negative patients. PFS was significantly lower in ERß-negative group. Further exploratory studies on larger sample sizes are required to validate these findings in NMIBC patients.
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BACKGROUND: Low- and middle-income countries bear a disproportionate burden of antimicrobial resistance (AMR) but often lack adequate surveillance to inform mitigation efforts. Colonization can be a useful metric to understand AMR burden. We assessed the colonization prevalence of Enterobacterales with resistance to extended-spectrum cephalosporins, carbapenems, colistin, and methicillin-resistant Staphylococcus aureus among hospital and community dwellers. METHODS: Between April and October 2019, we conducted a period prevalence study in Dhaka, Bangladesh. We collected stool and nasal specimens from adults in 3 hospitals and from community dwellers within the hospitals' catchment area. Specimens were plated on selective agar plates. Isolates underwent identification and antibiotic susceptibility testing using Vitek 2. We performed descriptive analysis and determined population prevalence estimates accounting for clustering at the community level. RESULTS: The majority of both community and hospital participants were colonized with Enterobacterales with resistance to extended-spectrum cephalosporins (78%; 95% confidence interval [95% CI], 73-83; and 82%; 95% CI, 79-85, respectively). Thirty-seven percent (95% CI, 34-41) of hospitalized patients were colonized with carbapenems compared with 9% (95% CI, 6-13) of community individuals. Colistin colonization prevalence was 11% (95% CI, 8-14) in the community versus 7% (95% CI, 6-10) in the hospital. Methicillin-resistant Staphylococcus aureus colonization was similar in both community and hospital participants (22%; 95% CI, 19-26 vs 21% (95% CI, 18-24). CONCLUSIONS: The high burden of AMR colonization observed among hospital and community participants may increase the risk for developing AMR infections and facilitating spread of AMR in both the community and hospital.
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Staphylococcus aureus Resistente a Meticilina , Infecciones Estafilocócicas , Adulto , Humanos , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Prevalencia , Colistina , Bangladesh/epidemiología , Hospitales , Carbapenémicos , Cefalosporinas , Farmacorresistencia Microbiana , Infecciones Estafilocócicas/tratamiento farmacológico , Infecciones Estafilocócicas/epidemiologíaRESUMEN
Photon echoes in rare-earth-doped crystals are studied to understand the challenges of making broadband quantum memories using the atomic frequency comb (AFC) protocol in systems with hyperfine structure. The hyperfine structure of Pr3+ poses an obstacle to this goal because frequencies associated with the hyperfine transitions change the simple picture of modulation at an externally imposed frequency. The current work focuses on the intermediate case where the hyperfine spacing is comparable to the comb spacing, a challenging regime that has recently been considered. Operating in this regime may facilitate storing quantum information over a larger spectral range in such systems. In this work, we prepare broadband AFCs using optical combs with tooth spacings ranging from 1 MHz to 16 MHz in fine steps, and measure transmission spectra and photon echoes for each. We predict the spectra and echoes theoretically using the optical combs as input to either a rate equation code or a density matrix code, which calculates the redistribution of populations. We then use the redistributed populations as input to a semiclassical theory using the frequency-dependent dielectric function. The two sets of predictions each give a good, but different account of the photon echoes.
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BACKGROUND: The Centers for Disease Control and Prevention (CDC) recommends testing patients with chlamydia (CT)/gonorrhea (GC) for other sexually transmitted infections (STIs) and repeating CT/GC testing 3 to 12 months later. We assessed repeat CT/GC testing and testing for HIV/syphilis in accordance with CDC guidelines in the US Veterans Health Administration. METHODS: Molecular laboratory testing for CT/GC during January 1, 2013-December 31, 2020 was retrieved from Veterans Health Administration data sources. Patients were evaluated for syphilis, HIV, and repeat CT/GC testing within 1 year after a positive CT/GC test result. Differences of CT/GC-positive patients associated with receiving recommended testing were assessed using χ2 /Fisher exact tests. RESULTS: A total of 41,630 of 1,005,761 CT (4.1%) and 17,649 of 1,013,198 GC (1.7%) results were positive. Median ages of positive CT/GC patients were 29 and 36 years, respectively. Repeat testing rates for CT/GC within 90 to 119 days were 3.9% and 2.9%, and rates within 90 to 365 days were 32.8% and 34.7%, with 8.6% and 15% being positive again, respectively. Guideline-compatible repeat testing in known HIV-positive patients nearly doubled (75.7% for CT and 67.8% for GC). The CDC-recommended HIV testing was performed for 72.4% and 65.5% CT and GC first positives, respectively, whereas syphilis testing was completed for 66.5% and 60.5% CT and GC, respectively. Compared with 25- to 34-year-old patients with CT or GC, those younger than 25 years had higher odds of guideline-discordant repeat testing but had lower odds of not receiving HIV/syphilis testing. CONCLUSIONS: Nearly two-thirds of patients did not receive recommended repeat testing, and nearly one-third were not tested for HIV/syphilis. Veterans Health Administration providers may benefit from additional education on CDC-recommended sexually transmitted infection guidelines and testing recommendations.
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Infecciones por Chlamydia , Chlamydia , Gonorrea , Infecciones por VIH , Enfermedades de Transmisión Sexual , Sífilis , Humanos , Adulto , Gonorrea/diagnóstico , Gonorrea/epidemiología , Sífilis/diagnóstico , Sífilis/epidemiología , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/epidemiología , Estudios de Seguimiento , Salud de los Veteranos , Infecciones por VIH/diagnóstico , Infecciones por VIH/epidemiologíaRESUMEN
The characteristics of dairy products, such as texture, color, flavor, and nutritional profile, are significantly influenced by the presence of milk fat. However, saturated fatty acids account for 65% of total milk fat. With increased health awareness and regulatory recommendations, consumer preferences have evolved toward low/no saturated fat food products. Reducing the saturated fat content of dairy products to meet market demands is an urgent yet challenging task, as it may compromise product quality and increase production costs. In this regard, oleogels have emerged as a viable milk fat replacement in dairy foods. This review focuses on recent advances in oleogel systems and explores their potential for incorporation into dairy products as a milk fat substitute. Overall, it can be concluded that oleogel can be a potential alternative to replace milk fat fully or partially in the product matrix to improve nutritional profile by mimicking similar rheological and textural product characteristics as milk fat. Furthermore, the impact of consuming oleogel-based dairy foods on digestibility and gut health is also discussed. A thorough comprehension of the application of oleogels in dairy products will provide an opportunity for the dairy sector to develop applications that will appeal to the changing consumer needs.
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The detrimental effects of adverse environmental conditions are always challenging and remain a major concern for plant development and production worldwide. Plants deal with such constraints by physiological, biochemical, and morphological adaptations as well as acquiring mutual support of beneficial microorganisms. As many stress-responsive traits of plants are influenced by microbial activities, plants have developed a sophisticated interaction with microbes to cope with adverse environmental conditions. The production of numerous bioactive metabolites by rhizospheric, endo-, or epiphytic microorganisms can directly or indirectly alter the root system architecture, foliage production, and defense responses. Although plant-microbe interactions have been shown to improve nutrient uptake and stress resilience in plants, the underlying mechanisms are not fully understood. "Multi-omics" application supported by genomics, transcriptomics, and metabolomics has been quite useful to investigate and understand the biochemical, physiological, and molecular aspects of plant-microbe interactions under drought stress conditions. The present review explores various microbe-mediated mechanisms for drought stress resilience in plants. In addition, plant adaptation to drought stress is discussed, and insights into the latest molecular techniques and approaches available to improve drought-stress resilience are provided.
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Sequías , Desarrollo de la Planta , Plantas , Perfilación de la Expresión Génica , Fenotipo , Estrés Fisiológico/fisiologíaRESUMEN
Introduction: Oligometastatic prostate cancer (OMPC) has gained profound interest lately due to its different tumor biology and our ability to use multimodality therapy for cure or prolonged survival. Selecting the appropriate patient for treatment has become the aim of treating urologists, medical oncologists, and radiation oncologists. Through this review, we try to highlight the management of OMPC in light of recent literature. Methods: Literature search was performed on Pubmed, Scopus and Embase using keywords "Oligometastatic", " Prostate Cancer" using operators such as "And" & "Or". Relevant articles were screened and all the latest articles on this emerging entity were included in this review. Results: All trials relevant to oligometastatic prostate cancer defining the role of surgery, radiotherapy and systemic therapy were included and appropriate inferences were drawn. Relevant studies were compiled in tabular form for this article. Conclusion: The current standard of care of management for OMPC remains systemic therapy on the lines of hormone-sensitive metastatic prostate cancer. The evolving role of surgery, and radiotherapy along with systemic therapy is highlighted in this article.
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BACKGROUND: We evaluated the effectiveness of mRNA-based vaccines following emergence of SARS-CoV-2 Omicron variant. METHODS: Recipients of a third dose of BNT162b2 or mRNA-1273 ≥180 days after the primary series were matched to primary-series recipients and unvaccinated persons. Participants were followed from 1 December 2021 to 12 March 2022. Outcomes were documented SARS-CoV-2 infection, COVID-19 hospitalization, and COVID-19 death. Effectiveness was calculated from 100-day risks estimated with the Kaplan-Meier estimator. RESULTS: BNT162b2 and mRNA-1273 groups included 221 267 and 187 507 third-dose recipients, respectively, matched to equal numbers of primary-series recipients and unvaccinated persons. Compared with no vaccination, effectiveness of a third dose of BNT162b2 was 47.8% (95% confidence interval [CI], 45.2-50.3), 81.8% (95% CI, 79.2-84.2), and 89.6% (95% CI, 85.0-93.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of BNT162b2 compared with the primary series was 30.1% (95% CI, 26.2-33.7), 61.4% (95% CI, 55.0-67.1), and 78.8% (95% CI, 67.9-87.5) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with no vaccination was 61.9% (95% CI, 59.4-64.4), 87.9% (95% CI, 85.3-90.2), and 91.4% (95% CI, 86.4-95.6) against infection, hospitalization, and death, respectively. Effectiveness of a third dose of mRNA-1273 compared with the primary series was 37.1% (95% CI, 32.2-41.7), 63.5% (95% CI, 53.7-71.6), and 75.0% (95% CI, 55.4-88.0) against infection, hospitalization, and death, respectively. CONCLUSIONS: BNT162b2 and mRNA-1273 were effective against COVID-19 following emergence of Omicron variant. A third dose provided additional protection over the primary series.
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COVID-19 , Vacunas de ARNm , Humanos , Vacuna BNT162 , SARS-CoV-2 , Vacuna nCoV-2019 mRNA-1273 , ARN MensajeroRESUMEN
There are many structural problems facing the UK at present, from a weakened National Health Service to deeply ingrained inequality. These challenges extend through society to clinical practice and have an impact on current mental health research, which was in a perilous state even before the coronavirus pandemic hit. In this editorial, a group of psychiatric researchers who currently sit on the Academic Faculty of the Royal College of Psychiatrists and represent the breadth of research in mental health from across the UK discuss the challenges faced in academic mental health research. They reflect on the need for additional investment in the specialty and ask whether this is a turning point for the future of mental health research.
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Objectives. To determine characteristics and sources of exposure in veterans with elevated blood lead levels (BLLs). Methods. We included users of US Veterans Health Administration care aged 18 years or older tested for BLL from October 2015 to September 2021. Prevalence of BLL 10 micrograms per deciliter (µg/dL) or higher and 25 µg/dL or higher was determined within demographic groups. Logistic regression analysis measured association of International Classification of Diseases, Tenth Revision, Clinical Modificationâcoded conditions with elevated BLL. Electronic notes were reviewed for exposure sources. Results. Among 1007 unique veterans with BLL 10 µg/dL or higher, prevalence of BLL 10 µg/dL or higher and 25 µg/dL or higher peaked at 4.9 and 1.3 per 100 000 veterans, respectively (fiscal year 2019), and was highest in non-Hispanic White men and those aged 25 to 34 years. Conditions predicted by elevated BLL were attention-deficit/hyperactivity disorder (ADHD) and nausea or vomiting. Firearms represented 70.1% of occupational and 85.9% of nonoccupational exposures. Toxicology consults occurred in 17 of 298 (6%) with BLL 25 µg/dL or higher. Conclusions. Firearms were the largest exposure source among veterans with elevated BLL. Clinicians should be alert for potential conditions (including ADHD and nausea or vomiting in our study) associated with lead exposure. Standardization of care regarding toxicology referral practices is warranted. (Am J Public Health. 2022;112(S7):S670-S678. https://doi.org/10.2105/AJPH.2022.306936).
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Intoxicación por Plomo , Veteranos , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Plomo , Intoxicación por Plomo/epidemiología , Masculino , Náusea , Estados Unidos/epidemiología , VómitosRESUMEN
PURPOSE: To assess the surgical outcomes of augmentation urethroplasty (AU) using penile skin graft (PSG) compared to buccal mucosa graft (BMG) in anterior urethral stricture disease. METHOD: Between January 2018 and January 2019, 100 patients with anterior urethral stricture planned for AU were randomized into PSG or BMG arms (CTRI/2018/07/015028). Anatomic and functional variables were compared pre-operatively and post-operatively. Primary outcome was success rate at 18 months and it was defined if any of the three criteria were met, i.e. either maximum urinary flow (Qmax) > 15 ml/s or urethral calibration of 16 French or ability to traverse the repair with 17 French cystoscope. Secondary outcomes were functional parameters such as International Prostate Symptom Score (IPSS), International Index of Erectile Function (IIEF) Score, Male Sexual Health Questionnaire for Ejaculatory Dysfunction (MSHQ-EJD), and Urethral Stricture Surgery-Patient Related Outcome Measure (USS-PROM). RESULTS: Pre-operative variables were comparable between both the arms. Median duration of follow-up was 22 months (18-24 months). At 18 months, the success rates of AU with PSG and BMG were comparable (89% v/s 91%; p = 0.70, 95% CI-0.33 to 5.21). The improvements in Qmax (p = 0.06), IPSS (p = 0.43) and USS-PROM (p = 0.49) were comparable between the two arms. There was no statistically significant difference in the IIEF-Erectile domain (p = 0.07), IIEF-Orgasmic domain (p = 0.11) and MSHQ-EJD (p = 0.20) following AU at 18 months. Clavien-Dindo grade I complications were 12.7% in PSG and 16.7% in BMG. CONCLUSION: This study provides level 1 evidence of no statistical significant difference in outcomes of AU using BMG or PSG.