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1.
Cureus ; 16(4): e57480, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38707098

RESUMO

OBJECTIVE: To determine the factors that might limit Hispanic patients from participating in dermatological clinical trials. METHODS: From January 2022 to July 2022, we administered a 31-item, in-person questionnaire to patients recruited in the waiting area of the Caridad Center, one of the largest free clinics in the United States with a predominately Hispanic population, and a nearby private primary care clinic. RESULTS: Overall, Hispanic patients agreed significantly more with statements in the domain of attitude and behavioral beliefs compared to non-Hispanic survey respondents. The Hispanic ethnicity was associated with increased odds of agreeing with the following statements: "My community would really benefit from skin cancer clinical trials" (OR=0.52; 95% CI 0.30, 0.92), "My participation in a skin cancer study would be very good" (OR=0.59; 95% CI 0.35, 0.99), and "I like to do good for others" (OR=0.41; 95% CI 0.22, 0.77). CONCLUSION: While the United States population is composed of 18.5% Hispanics, they only account for 1% of patients enrolled in clinical trials. This study helps identify potential motivational factors for Hispanic patients to participate in skin cancer clinical trials.

2.
Front Immunol ; 15: 1343716, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38605956

RESUMO

Background: Cross-reactive SARS-CoV-2-specific memory CD4+ and CD8+ T cells are present in up to 50% of unexposed, pre-pandemic, healthy individuals (UPPHIs). However, the characteristics of cross-reactive memory CD4+ and CD8+ T cells associated with subsequent protection of asymptomatic coronavirus disease 2019 (COVID-19) patients (i.e., unvaccinated individuals who never develop any COVID-19 symptoms despite being infected with SARS-CoV-2) remains to be fully elucidated. Methods: This study compares the antigen specificity, frequency, phenotype, and function of cross-reactive memory CD4+ and CD8+ T cells between common cold coronaviruses (CCCs) and SARS-CoV-2. T-cell responses against genome-wide conserved epitopes were studied early in the disease course in a cohort of 147 unvaccinated COVID-19 patients who were divided into six groups based on the severity of their symptoms. Results: Compared to severely ill COVID-19 patients and patients with fatal COVID-19 outcomes, the asymptomatic COVID-19 patients displayed significantly: (i) higher rates of co-infection with the 229E alpha species of CCCs (α-CCC-229E); (ii) higher frequencies of cross-reactive functional CD134+CD137+CD4+ and CD134+CD137+CD8+ T cells that cross-recognized conserved epitopes from α-CCCs and SARS-CoV-2 structural, non-structural, and accessory proteins; and (iii) lower frequencies of CCCs/SARS-CoV-2 cross-reactive exhausted PD-1+TIM3+TIGIT+CTLA4+CD4+ and PD-1+TIM3+TIGIT+CTLA4+CD8+ T cells, detected both ex vivo and in vitro. Conclusions: These findings (i) support a crucial role of functional, poly-antigenic α-CCCs/SARS-CoV-2 cross-reactive memory CD4+ and CD8+ T cells, induced following previous CCCs seasonal exposures, in protection against subsequent severe COVID-19 disease and (ii) provide critical insights into developing broadly protective, multi-antigen, CD4+, and CD8+ T-cell-based, universal pan-Coronavirus vaccines capable of conferring cross-species protection.


Assuntos
COVID-19 , Resfriado Comum , Humanos , SARS-CoV-2 , Antígeno CTLA-4 , Linfócitos T CD8-Positivos , Células T de Memória , Receptor Celular 2 do Vírus da Hepatite A , Receptor de Morte Celular Programada 1 , Linfócitos T CD4-Positivos , Epitopos
3.
bioRxiv ; 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-38405942

RESUMO

The first-generation Spike-alone-based COVID-19 vaccines have successfully contributed to reducing the risk of hospitalization, serious illness, and death caused by SARS-CoV-2 infections. However, waning immunity induced by these vaccines failed to prevent immune escape by many variants of concern (VOCs) that emerged from 2020 to 2024, resulting in a prolonged COVID-19 pandemic. We hypothesize that a next-generation Coronavirus (CoV) vaccine incorporating highly conserved non-Spike SARS-CoV-2 antigens would confer stronger and broader cross-protective immunity against multiple VOCs. In the present study, we identified ten non-Spike antigens that are highly conserved in 8.7 million SARS-CoV-2 strains, twenty-one VOCs, SARS-CoV, MERS-CoV, Common Cold CoVs, and animal CoVs. Seven of the 10 antigens were preferentially recognized by CD8+ and CD4+ T-cells from unvaccinated asymptomatic COVID-19 patients, irrespective of VOC infection. Three out of the seven conserved non-Spike T cell antigens belong to the early expressed Replication and Transcription Complex (RTC) region, when administered to the golden Syrian hamsters, in combination with Spike, as nucleoside-modified mRNA encapsulated in lipid nanoparticles (LNP) (i.e., combined mRNA/LNP-based pan-CoV vaccine): (i) Induced high frequencies of lung-resident antigen-specific CXCR5+CD4+ T follicular helper (TFH) cells, GzmB+CD4+ and GzmB+CD8+ cytotoxic T cells (TCYT), and CD69+IFN-γ+TNFα+CD4+ and CD69+IFN-γ+TNFα+CD8+ effector T cells (TEFF); and (ii) Reduced viral load and COVID-19-like symptoms caused by various VOCs, including the highly pathogenic B.1.617.2 Delta variant and the highly transmittable heavily Spike-mutated XBB1.5 Omicron sub-variant. The combined mRNA/LNP-based pan-CoV vaccine could be rapidly adapted for clinical use to confer broader cross-protective immunity against emerging highly mutated and pathogenic VOCs.

4.
BMC Infect Dis ; 23(1): 330, 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37194021

RESUMO

BACKGROUND: While others have reported severe acute respiratory syndrome-related coronavirus 2(SARS-CoV-2) seroprevalence studies in health care workers (HCWs), we leverage the use of a highly sensitive coronavirus antigen microarray to identify a group of seropositive health care workers who were missed by daily symptom screening that was instituted prior to any epidemiologically significant local outbreak. Given that most health care facilities rely on daily symptom screening as the primary method to identify SARS-CoV-2 among health care workers, here, we aim to determine how demographic, occupational, and clinical variables influence SARS-CoV-2 seropositivity among health care workers. METHODS: We designed a cross-sectional survey of HCWs for SARS-CoV-2 seropositivity conducted from May 15th to June 30th 2020 at a 418-bed academic hospital in Orange County, California. From an eligible population of 5,349 HCWs, study participants were recruited in two ways: an open cohort, and a targeted cohort. The open cohort was open to anyone, whereas the targeted cohort that recruited HCWs previously screened for COVID-19 or work in high-risk units. A total of 1,557 HCWs completed the survey and provided specimens, including 1,044 in the open cohort and 513 in the targeted cohort. Demographic, occupational, and clinical variables were surveyed electronically. SARS-CoV-2 seropositivity was assessed using a coronavirus antigen microarray (CoVAM), which measures antibodies against eleven viral antigens to identify prior infection with 98% specificity and 93% sensitivity. RESULTS: Among tested HCWs (n = 1,557), SARS-CoV-2 seropositivity was 10.8%, and risk factors included male gender (OR 1.48, 95% CI 1.05-2.06), exposure to COVID-19 outside of work (2.29, 1.14-4.29), working in food or environmental services (4.85, 1.51-14.85), and working in COVID-19 units (ICU: 2.28, 1.29-3.96; ward: 1.59, 1.01-2.48). Amongst 1,103 HCWs not previously screened, seropositivity was 8.0%, and additional risk factors included younger age (1.57, 1.00-2.45) and working in administration (2.69, 1.10-7.10). CONCLUSION: SARS-CoV-2 seropositivity is significantly higher than reported case counts even among HCWs who are meticulously screened. Seropositive HCWs missed by screening were more likely to be younger, work outside direct patient care, or have exposure outside of work.


Assuntos
COVID-19 , SARS-CoV-2 , Humanos , Masculino , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Estudos Soroepidemiológicos , Pessoal de Saúde , Anticorpos Antivirais
5.
Am J Surg ; 224(6): 1468-1472, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36008169

RESUMO

BACKGROUND: This study aimed to investigate the disparity between white and minority patients undergoing cholecystectomies, including presentation, outcomes, and financial burden. METHODS: This was an IRB approved retrospective review of all cholecystectomies at an academic medical center from 2013 to 2018. Data collected include demographics, insurance type, charge of admission, and clinical outcomes. RESULTS: 1539 patients underwent cholecystectomies. Of those, 36.9% were white and 63.1% were minority. Minority patients presented at a younger age than white patients (45.5 vs 53.9, p < 0.01) and required emergent admission (76.2% vs 68.4%, p < 0.01). No significant difference was found for clinical outcomes between white and minority. Minority patients were more commonly uninsured (32.1%). Among the uninsured, self-pay had a higher charge than emergency MediCal (by 5.46 per 1000 dollars). CONCLUSION: Minority patients are more commonly disadvantaged at presentation and charged more due to insurance status despite similar outcomes after cholecystectomies.


Assuntos
Colecistectomia , Humanos , Cobertura do Seguro , Pessoas sem Cobertura de Seguro de Saúde , Estudos Retrospectivos , Resultado do Tratamento , Brancos , Minorias Étnicas e Raciais , Determinantes Sociais da Saúde
6.
Curr Opin Infect Dis ; 35(4): 295-301, 2022 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-35849519

RESUMO

PURPOSE OF REVIEW: To describe the state-of-the-art of telemedicine in hematology through the description of most relevant studies published in the pre-COVID19 and during the COVID19 era. RECENT FINDINGS: Telemedicine has recently gained momentum in hematology due to the COVID19 pandemic. Due to a necessary improvement of domiciliary follow-up of patients during the pandemic and an increase in technologies able to offer telemedicine, the number of studies has increased in the last 2 years. Telemedicine showed the potential to improve the monitoring of both benign and malignant hematological diseases. Patients affected by thalassemias, hemophilias and/or myeloproliferative diseases were monitored successfully with telemedicine platform. For higher-risk patients such as high-dose chemotherapy or stem cell transplantation, better platforms are needed (e.g. use of wearable devices systems). Also, telemedicine showed to be useful for the follow-up of hematological patients with COVID19. SUMMARY: Despite the clear potential advantages of telemedicine for the follow-up of hematological patients, more evidence is required before adopting this approach in larger cohorts of patients. Larger- and higher-quality studies are highly needed in this setting.


Assuntos
COVID-19 , Telemedicina , COVID-19/epidemiologia , Europa (Continente)/epidemiologia , Humanos , Pandemias
7.
J Vector Borne Dis ; 59(1): 86-90, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35708409

RESUMO

The recently described Triatoma huehuetenanguensis, has been reported in Mexico, Guatemala, Belize and Honduras. In Mexico, the species has been collected primarily in rural areas; it has the potential to colonize human dwellings, however, its contribution to Chagas outbreaks remains unclear. In 2021, T. huehuetenanguensis was first observed at Tuxtla Gutierrez city, Chiapas; then a collection for the species was performed. A total of 308 houses were inspected in the intra and peridomestic structures. Only 3 houses (0.97%) were infested. Triatoma huehuetenangensis was the only triatomine specie recorded and four males were collected. None of the bugs tested positive for Trypanosoma infection. We do not have evidence to suggest that urban human-vector contact still limited, and a possible domestication process is possible. The presence of reservoirs, the vector species and the parasite demonstrate that Tuxtla Gutierrez could be at risk of a Chagas disease outbreak.


Assuntos
Doença de Chagas , Triatoma , Trypanosoma cruzi , Animais , Doença de Chagas/epidemiologia , Humanos , Insetos Vetores/parasitologia , Masculino , México/epidemiologia , Triatoma/parasitologia
8.
Appl Radiat Isot ; 187: 110331, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35764005

RESUMO

Exposure of biological systems to a radiation absorbed dose produces early and late radiogenic responses, such as ion channel modulation, oxidative stress, cell migration enhancement, and metabolic changes that could impact the efficiency of radiotherapy. To understand how radiation modulates ion channels, we irradiated HEK cells stably expressing the human ether à-go-go potassium channel-1 with gamma photons in the dose range of 2-10 Gy (60Co, 0.2 Gy/min) and measured ionic currents generated by the channel. The importance of the Kv10.1 modulation by gamma radiation was studied using cell proliferation. Results showed that a radiation-absorbed dose of 4 Gy significantly reduced the Kv10.1-evoked currents by depolarizing pulses between -100 mV and +50 mV. Additionally, the expression of Kv10.1 positively modulates HEK293 proliferation and, certainly, prevents the effect of gamma radiation on this phenomenon. Results allow concluding that the modulation of the functional expression of the Kv10.1 channel, induced by gamma radiation, leads to the expression of a radioresistant phenotype in Kv10.1 expressing cells.


Assuntos
Raios gama , Proliferação de Células , Células HEK293 , Humanos
9.
Front Immunol ; 13: 817345, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35493473

RESUMO

Recent studies provide conflicting evidence on the persistence of SARS-CoV-2 immunity induced by mRNA vaccines. Here, we aim to quantify the persistence of humoral immunity following vaccination using a coronavirus antigen microarray that includes 10 SARS-CoV-2 antigens. In a prospective longitudinal cohort of 240 healthcare workers, composite SARS-CoV-2 IgG antibody levels did not wane significantly over a 6-month study period. In the subset of the study population previously exposed to SARS-CoV-2 based on seropositivity for nucleocapsid antibodies, higher composite anti-spike IgG levels were measured before the vaccine but no significant difference from unexposed individuals was observed at 6 months. Age, vaccine type, or worker role did not significantly impact composite IgG levels, although non-significant trends towards lower antibody levels in older participants and higher antibody levels with Moderna vaccine were observed at 6 months. A small subset of our cohort were classified as having waning antibody titers at 6 months, and these individuals were less likely to work in patient care roles and more likely to have prior exposure to SARS-CoV-2.


Assuntos
COVID-19 , SARS-CoV-2 , Idoso , Anticorpos Antivirais , COVID-19/prevenção & controle , Pessoal de Saúde , Humanos , Imunoglobulina G , Lactente , Estudos Prospectivos
10.
Antimicrob Resist Infect Control ; 10(1): 163, 2021 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-34809702

RESUMO

BACKGROUND: Early evaluations of healthcare professional (HCP) COVID-19 risk occurred during insufficient personal protective equipment and disproportionate testing, contributing to perceptions of high patient-care related HCP risk. We evaluated HCP COVID-19 seropositivity after accounting for community factors and coworker outbreaks. METHODS: Prior to universal masking, we conducted a single-center retrospective cohort plus cross-sectional study. All HCP (1) seen by Occupational Health for COVID-like symptoms (regardless of test result) or assigned to (2) dedicated COVID-19 units, (3) units with a COVID-19 HCP outbreak, or (4) control units from 01/01/2020 to 04/15/2020 were offered serologic testing by an FDA-authorized assay plus a research assay against 67 respiratory viruses, including 11 SARS-CoV-2 antigens. Multivariable models assessed the association of demographics, job role, comorbidities, care of a COVID-19 patient, and geocoded socioeconomic status with positive serology. RESULTS: Of 654 participants, 87 (13.3%) were seropositive; among these 60.8% (N = 52) had never cared for a COVID-19 patient. Being male (OR 1.79, CI 1.05-3.04, p = 0.03), working in a unit with a HCP-outbreak unit (OR 2.21, CI 1.28-3.81, p < 0.01), living in a community with low owner-occupied housing (OR = 1.63, CI = 1.00-2.64, p = 0.05), and ethnically Latino (OR 2.10, CI 1.12-3.96, p = 0.02) were positively-associated with COVID-19 seropositivity, while working in dedicated COVID-19 units was negatively-associated (OR 0.53, CI = 0.30-0.94, p = 0.03). The research assay identified 25 additional seropositive individuals (78 [12%] vs. 53 [8%], p < 0.01). CONCLUSIONS: Prior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission. Prior to universal masking, HCP COVID-19 risk was dominated by workplace and community exposures while working in a dedicated COVID-19 unit was protective, suggesting that infection prevention protocols prevent patient-to-HCP transmission.


Assuntos
COVID-19/prevenção & controle , Pessoal de Saúde , Controle de Infecções , Centros Médicos Acadêmicos , Adulto , California/epidemiologia , Infecções Comunitárias Adquiridas , Estudos Transversais , Surtos de Doenças , Feminino , Humanos , Transmissão de Doença Infecciosa do Paciente para o Profissional/prevenção & controle , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Análise de Regressão , Estudos Retrospectivos , Fatores de Risco
11.
Am Surg ; 87(10): 1606-1611, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34388946

RESUMO

INTRODUCTION: Drug and alcohol consumption are often associated with trauma-related injuries. Various studies have been conducted which have shown the benefits of screening and brief intervention (SBI) tools for alcohol consumption. Despite their success, there are few SBI tools utilized for substance use and minimal reports of computerized versions. We hypothesized that a computerized SBI tool for drug use would be effective at identifying patients at risk of substance abuse in a trauma setting. METHODS: This was a prospective evaluation of a computerized alcohol and drug screening and brief intervention survey derived from the National Institute on Drug Abuse. The survey was given to all eligible trauma patients at UCI's Level 1 trauma facility between February 2019 and March 2020. Based on self-reported answers, a substance involvement (SI) score was generated which classified a patient's drug abuse risk as none (0), low (1-3), moderate (4-26), or high (27+). Statistical tests were then used to examine associations between demographic variables and risk categorization. RESULTS: A total of 1801 patients completed the entire survey. Of those, 346 (19.3%) patients reported use of illicit drugs: 10 for non-medical prescription use (.6%), 308 (17.1%) for non-prescription drug use, and 28 (1.6%) for both. Secondary analysis revealed a greater number of males were eligible for further SI assessment (25.1% vs 11.0%, P < .001). Of those, a greater proportion of men were classified as moderate/high risk (81.6% vs 61.5%, P < .001). Further breakdown revealed a greater proportion of patients ≤25 years old reported use of drugs compared to >85 years old (37.0% vs .5%, P < .001). In contrast to the self-reported data, there was an overall positive rate of toxicology of 48.51%. CONCLUSION: The analysis shows that the electronic survey identifies patients at risk of drug abuse, allowing for real-time intervention. Furthermore, it is granular enough to specify at-risk groups. However, a lower self-reported rate, as expected, was elucidated. Further studies to evaluate for improved screening and targeted intervention are warranted.


Assuntos
Detecção do Abuso de Substâncias/métodos , Centros de Traumatologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Inquéritos e Questionários , Estados Unidos
12.
Am Surg ; 87(10): 1594-1599, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34128407

RESUMO

INTRODUCTION: It remains unclear whether an increased mortality risk in uninsured patients exists across Injury Severity Score (ISS) classifications. We hypothesized that penetrating trauma self-pay patients would have a similarly increased mortality risk across all ISS categories. METHODS: The National Trauma Data Bank (2013-2015) was queried for patients presenting with penetrating firearm, explosive, or stab wound injuries. 115 651 patients were identified and a stratified multivariable logistic regression model was used. RESULTS: In the >15 ISS group, self-pay patients had a lower median total hospital Length of Stay (LOS) (3 vs 8, P < .001), lower median Intensive Care Unit LOS (1 vs 3, P < .001), and lower median ventilator days (0 vs 1, P < .001). Self-pay patients had an increased risk for mortality compared to patients with private insurance in both the ≤15 ISS group (OR 2.68, P < .001) and >15 ISS group (OR 1.56, P < .001). CONCLUSION: Uninsured patients have an increased mortality risk in both low and high ISS groups. A higher mortality risk among uninsured patients in the high ISS group can be explained by decreased resource availability and lower ICU days and ventilator time. However, more studies are needed to determine why there is an even greater mortality risk among uninsured patients with mild ISS.


Assuntos
Pessoas sem Cobertura de Seguro de Saúde , Ferimentos Penetrantes/mortalidade , Adulto , Idoso , Bases de Dados Factuais , Feminino , Mortalidade Hospitalar , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Fatores de Risco , Estados Unidos/epidemiologia
13.
Am Surg ; 87(10): 1600-1605, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34128413

RESUMO

INTRODUCTION: Extensive research relying on Injury Severity Scores (ISS) reports a mortality benefit from routine non-selective thoracic CTs (an integral part of pan-computed tomography (pan-CT)s). Recent research suggests this mortality benefit may be artifact. We hypothesized that the use of pan-CTs inflates ISS categorization in patients, artificially affecting admission rates and apparent mortality benefit. METHODS: Eight hundred and eleven patients were identified with an ISS >15 with significant findings in the chest area. Patient charts were reviewed and scores were adjusted to exclude only occult injuries that did not affect treatment plan. Pearson chi-square tests and multivariable logistic regression were used to compare adjusted cases vs non-adjusted cases. RESULTS: After adjusting for inflation, 388 (47.8%) patients remained in the same ISS category, 378 (46.6%) were reclassified into 1 lower ISS category, and 45 (5.6%) patients were reclassified into 2 lower ISS categories. Patients reclassified by 1 category had a lower rate of mortality (P < 0.001), lower median total hospital LOS (P < .001), ICU days (P < .001), and ventilator days (P = 0.008), compared to those that remained in the same ISS category. CONCLUSION: Injury Severity Score inflation artificially increases survival rate, perpetuating the increased use of pan-CTs. This artifact has been propagated by outdated mortality prediction calculation methods. Thus, prospective evaluations of algorithms for more selective CT scanning are warranted.


Assuntos
Traumatismos Torácicos/classificação , Traumatismos Torácicos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Ferimentos não Penetrantes/classificação , Ferimentos não Penetrantes/diagnóstico por imagem , Adulto , Feminino , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Traumatismos Torácicos/mortalidade , Centros de Traumatologia , Ferimentos não Penetrantes/mortalidade
14.
J Immunol ; 206(11): 2566-2582, 2021 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-33911008

RESUMO

Over the last two decades, there have been three deadly human outbreaks of coronaviruses (CoVs) caused by SARS-CoV, MERS-CoV, and SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats and transmitted to humans via various intermediate animal reservoirs. It remains highly possible that other global COVID pandemics will emerge in the coming years caused by yet another spillover of a bat-derived SARS-like coronavirus (SL-CoV) into humans. Determining the Ag and the human B cells, CD4+ and CD8+ T cell epitope landscapes that are conserved among human and animal coronaviruses should inform in the development of future pan-coronavirus vaccines. In the current study, using several immunoinformatics and sequence alignment approaches, we identified several human B cell and CD4+ and CD8+ T cell epitopes that are highly conserved in 1) greater than 81,000 SARS-CoV-2 genome sequences identified in 190 countries on six continents; 2) six circulating CoVs that caused previous human outbreaks of the common cold; 3) nine SL-CoVs isolated from bats; 4) nine SL-CoV isolated from pangolins; 5) three SL-CoVs isolated from civet cats; and 6) four MERS strains isolated from camels. Furthermore, the identified epitopes: 1) recalled B cells and CD4+ and CD8+ T cells from both COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2, and 2) induced strong B cell and T cell responses in humanized HLA-DR1/HLA-A*02:01 double-transgenic mice. The findings pave the way to develop a preemptive multiepitope pan-coronavirus vaccine to protect against past, current, and future outbreaks.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Epitopos de Linfócito T , Genoma Viral/imunologia , Coronavírus da Síndrome Respiratória do Oriente Médio , SARS-CoV-2 , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Epitopos de Linfócito T/genética , Epitopos de Linfócito T/imunologia , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/imunologia , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/genética , Coronavírus Relacionado à Síndrome Respiratória Aguda Grave/imunologia , SARS-CoV-2/genética , SARS-CoV-2/imunologia , Vacinas Virais/genética , Vacinas Virais/imunologia
15.
Chronobiol Int ; 38(2): 201-211, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33397171

RESUMO

Circadian rhythms are an adaptive response of organisms to the environment that enables them to measure time. Circadian rhythms are some of the most studied biological rhythms. Serotonin (5HT) has been proposed as their modulator of circadian rhythms, playing a pivotal role in their establishment. However, 5HT concentrations are altered in insect organisms when they feed on some plant extracts. Insects show a variety of rhythms. The larval stage of the lepidopteran Spodoptera frugiperda is a pest of economically important crops. As a response, plants have developed secondary metabolites, such as azadirachtin, obtained from Azadirachta indica. We assessed the circadian rhythm of 5HT in the brain and digestive tube of larvae of S. frugiperda; furthermore, the effect of A. indica extract on the oscillations was evaluated. 5HT modulates the rhythms of locomotor activity, and if extracts of A. indica alter the concentration of 5HT, it can indirectly alter the rhythms of locomotor activity, as well as peristaltic movements of the intestine. Larvae were exposed to a 12 h:12 h light-dark (LD) photoperiod, and half of them remained for 72 h under constant darkness (DD). Tissue samples were obtained at six different times during a single 24 h period, and the amount of 5HT was quantified by high-performance liquid chromatography (HPLC). Data were statistically compared by a one-way ANOVA followed by a Tukey post hoc test and subjected to Cosinor analysis for assessment of 24 h rhythmicity. The results showed that the A. indica methanolic extract had an effect on the 5HT concentration of the brain and digestive tube of the larvae. In the brain, the 5HT increase in larvae fed with the extract could alter memory, learning, sleep, and locomotor activity processes. Whereas in the intestine, the 5HT decrease in the larvae fed with the extract could decrease peristalsis movements and, therefore, indirectly influence the antifeedant effect.


Assuntos
Azadirachta , Meliaceae , Animais , Ritmo Circadiano , Serotonina , Spodoptera
16.
Am Surg ; 87(12): 1972-1979, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33380167

RESUMO

BACKGROUND: Traumatic brain injury (TBI) occurs in approximately 30% of trauma patients. Because neurosurgeons hold expertise in treating TBI, increased neurosurgical staffing may improve patient outcomes. We hypothesized that TBI patients treated at level I trauma centers (L1TCs) with ≥3 neurosurgeons have a decreased risk of mortality vs. those treated at L1TCs with <3 neurosurgeons. METHODS: The Trauma Quality Improvement Program database (2010-2016) was queried for patients ≥18 years with TBI. Patient characteristics and mortality were compared between ≥3 and <3 neurosurgeon-staffed L1TCs. A multivariable logistic regression analysis was used to identify risk factors associated with mortality. RESULTS: Traumatic brain injury occurred in 243 438 patients with 5188 (2%) presenting to L1TCs with <3 neurosurgeons and 238 250 (98%) to L1TCs with ≥3 neurosurgeons. Median injury severity score (ISS) was similar between both groups (17, P = .09). There were more Black (37% vs. 12%, P < .001) and Hispanic (18% vs. 12%, P < .001) patients in the <3 neurosurgeon group. Nearly 60% of L1TCs with <3 neurosurgeons are found in the South. Mortality was higher in the <3 vs. the ≥3 group (12% vs. 10%, P < .001). Patients treated in the <3 neurosurgeon group had a higher risk for mortality than those treated in the ≥3 neurosurgeon group (odds ratio (OR) 1.13, 95% confidence intervals (CI) 1.01-1.26, P = .028). DISCUSSION: There exists a significant racial disparity in access to neurosurgeon staffing with additional disparities in outcomes based on staffing. Future efforts are needed to improve this chasm of care that exists for trauma patients of color.


Assuntos
Lesões Encefálicas Traumáticas/terapia , Disparidades em Assistência à Saúde , Neurocirurgiões/provisão & distribuição , Avaliação de Resultados em Cuidados de Saúde , Fatores Raciais , Centros de Traumatologia/normas , Recursos Humanos , Adulto , População Negra , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/etnologia , Lesões Encefálicas Traumáticas/mortalidade , Cuidados Críticos , Feminino , Hispânico ou Latino , Mortalidade Hospitalar , Humanos , Escala de Gravidade do Ferimento , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Centros de Traumatologia/organização & administração
17.
Molecules ; 26(1)2020 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-33374385

RESUMO

This study aimed to obtain a third-generation snack from native rice starch (NS), rice starch modified by extrusion (MS), nopal flour (NF) and xanthan gum (XG). These raw materials were characterized by proximal analysis, pH, particle size distribution, water absorption index (WAI) and water solubility index (WSI), degree of substitution (DS), differential scanning calorimetry (DSC), rheology, Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The analysis of the response variables in the nine formulations of the snack: expansion index (EI), apparent density (AD), hardness (H), luminosity (L*) and tendency to green-red (a*), was performed through a composite central design (CCD), the selected formulations were characterized by SEM. Results showed an increase in WAI, 4.69 ± 0.04, and WSI, 12.61 ± 0.10, for MS, higher than NS values due to chemical modification. According to the color analysis the NF obtained a value of 60.73 ± 0.008 in L* and -6.51 ± 0.004 in a* with green tendency. The DS value obtained was 0.09 ± 0.005, being within the FDA's permissible range for food use. By FTIR analysis, the acetyl group was corroborated. Finally, employing microwave cooking, snacks made from NS with concentrations of NF (5%) and XG (0%) obtained the highest EI value, 4.47, as well the low Dap and D value (0.37 g/cm3, 2.25 N, respectively), corroborated by SEM analysis.


Assuntos
Farinha/análise , Opuntia/química , Oryza/química , Lanches , Amido/química , Algoritmos , Fenômenos Químicos , Análise de Alimentos , Modelos Teóricos , Solubilidade , Análise Espectral , Amido/ultraestrutura
18.
bioRxiv ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-33024971

RESUMO

Over the last two decades, there have been three deadly human outbreaks of Coronaviruses (CoVs) caused by emerging zoonotic CoVs: SARS-CoV, MERS-CoV, and the latest highly transmissible and deadly SARS-CoV-2, which has caused the current COVID-19 global pandemic. All three deadly CoVs originated from bats, the natural hosts, and transmitted to humans via various intermediate animal reservoirs. Because there is currently no universal pan-Coronavirus vaccine available, two worst-case scenarios remain highly possible: (1) SARS-CoV-2 mutates and transforms into a seasonal "flu-like" global pandemic; and/or (2) Other global COVID-like pandemics will emerge in the coming years, caused by yet another spillover of an unknown zoonotic bat-derived SARS-like Coronavirus (SL-CoV) into an unvaccinated human population. Determining the antigen and epitope landscapes that are conserved among human and animal Coronaviruses as well as the repertoire, phenotype and function of B cells and CD4 + and CD8 + T cells that correlate with resistance seen in asymptomatic COVID-19 patients should inform in the development of pan-Coronavirus vaccines 1 . In the present study, using several immuno-informatics and sequence alignment approaches, we identified several human B-cell, CD4 + and CD8 + T cell epitopes that are highly conserved in: ( i ) greater than 81,000 SARS-CoV-2 human strains identified to date in 190 countries on six continents; ( ii ) six circulating CoVs that caused previous human outbreaks of the "Common Cold"; ( iii ) five SL-CoVs isolated from bats; ( iv ) five SL-CoV isolated from pangolins; ( v ) three SL-CoVs isolated from Civet Cats; and ( vi ) four MERS strains isolated from camels. Furthermore, we identified cross-reactive asymptomatic epitopes that: ( i ) recalled B cell, CD4 + and CD8 + T cell responses from both asymptomatic COVID-19 patients and healthy individuals who were never exposed to SARS-CoV-2; and ( ii ) induced strong B cell and T cell responses in "humanized" Human Leukocyte Antigen (HLA)-DR/HLA-A*02:01 double transgenic mice. The findings herein pave the way to develop a pre-emptive multi-epitope pan-Coronavirus vaccine to protect against past, current, and potential future outbreaks.

19.
Am Surg ; 86(10): 1264-1268, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33076680

RESUMO

Diabetes mellitus (DM) and hypertension (HTN) are increasing in prevalence in the population. Level 1 trauma facilities are often faced with managing these chronic conditions. Recent studies indicated that 12-44% of patients presenting traumas are found to have incidental findings by imaging representing undiagnosed medical conditions, with 10% reported requiring further management [Surendran A, Mori A, Varma DK, Gruen RL. Systematic review of the benefits and harms of whole-body computed tomography in the early management of multitrauma patients: Are we getting the whole picture? J Trauma and Acute Care Surg. 2014;76(4):1122-1130]. Between 2015 and 2016, 852 patients seen at a level 1 trauma center were analyzed. Patients were evaluated who received a new diagnosis of HTN or DM, or had preexisting diagnosis of HTN or DM whose management was changed. Uncontrolled HTN or DM was defined as a need for either a change in medication or primary care optimization prior to discharge. Among the patients evaluated, 6.3% and 3.0% received new diagnoses of HTN and DM, respectively. Additionally, 34.4% and 35.3% of patients were found to have uncontrolled HTN and DM and required medical optimization, respectively. The high prevalence of undiagnosed or suboptimal management for chronic conditions indicates that more research is warranted for defining, screening for, and treating surgical patients with poorly controlled medical conditions with these comorbidities.


Assuntos
Diabetes Mellitus/diagnóstico , Diabetes Mellitus/tratamento farmacológico , Hipertensão/diagnóstico , Hipertensão/tratamento farmacológico , Centros de Traumatologia , Adulto , Idoso , Anti-Hipertensivos/uso terapêutico , Doença Crônica , Demografia , Feminino , Humanos , Hipoglicemiantes/uso terapêutico , Achados Incidentais , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
20.
Nat Med ; 26(8): 1218-1223, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32581323

RESUMO

As of 10 April 2020, New York State had 180,458 cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and 9,385 reported deaths. Patients with cancer comprised 8.4% of deceased individuals1. Population-based studies from China and Italy suggested a higher coronavirus disease 2019 (COVID-19) death rate in patients with cancer2,3, although there is a knowledge gap as to which aspects of cancer and its treatment confer risk of severe COVID-194. This information is critical to balance the competing safety considerations of reducing SARS-CoV-2 exposure and cancer treatment continuation. From 10 March to 7 April 2020, 423 cases of symptomatic COVID-19 were diagnosed at Memorial Sloan Kettering Cancer Center (from a total of 2,035 patients with cancer tested). Of these, 40% were hospitalized for COVID-19, 20% developed severe respiratory illness (including 9% who required mechanical ventilation) and 12% died within 30 d. Age older than 65 years and treatment with immune checkpoint inhibitors (ICIs) were predictors for hospitalization and severe disease, whereas receipt of chemotherapy and major surgery were not. Overall, COVID-19 in patients with cancer is marked by substantial rates of hospitalization and severe outcomes. The association observed between ICI and COVID-19 outcomes in our study will need further interrogation in tumor-specific cohorts.


Assuntos
Infecções por Coronavirus/mortalidade , Neoplasias/mortalidade , Pandemias , Pneumonia Viral/mortalidade , Adolescente , Adulto , Idoso , Betacoronavirus/patogenicidade , COVID-19 , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Feminino , Hospitalização , Humanos , Itália/epidemiologia , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Neoplasias/patologia , Neoplasias/virologia , Pneumonia Viral/complicações , Pneumonia Viral/patologia , Pneumonia Viral/virologia , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Estados Unidos/epidemiologia , Adulto Jovem
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