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BACKGROUND: Whether variation in Medicaid reimbursement fees influenced the impacts of the Medicaid expansions is not well understood. OBJECTIVE: We examine whether changes in health care access associated with Medicaid expansion are different in states with comparatively high Medicaid reimbursement rates compared against expanding in states with lower Medicaid reimbursement rates. DESIGN: Using a difference-in-difference-in-difference (DDD or triple-difference) regression approach, we compare relative differences in Medicaid expansion effects between lower and higher reimbursement states. PARTICIPANTS: 512,744 low-income adults aged 20-64 in the 2011-2019 Behavioral Risk Factor Surveillance System. MAIN MEASURES: Health insurance coverage status, unmet medical needs due to cost, regular source for health care, and a regular/scheduled checkup within the past year. KEY RESULTS: Medicaid expansion has significant and positive impacts on health coverage and access in both high- and low-fee states. In states with fee levels above the median Medicare-to-Medicaid ratios, expanding Medicaid eligibility reduced uninsurance rate by 15.2 percentage point (ppt, p < 0.01), shrank the cost-associated unmet medical need by 10.3 ppt (p < 0.01), improved access to usual source of care by 1.9 ppt (p < 0.1), and increased regular checkup by 14.4 ppt (p < 0.01), while such effects in low-fee states were 11.7 ppt (p < 0.01), 8.3 ppt (p < 0.01), 3.1 ppt (p < 0.1), and 12.3 ppt (p < 0.01), respectively. Our results suggest that Medicaid expansion effect on unmet medical need due to cost in higher-reimbursing states was 2.98 ppt (p < 0.05) larger than in lower-reimbursing states. Evidence suggests modest increases in health care access were more strongly associated with expansions in higher-fee states. CONCLUSIONS: Medicaid's fee structure should be considered as a factor influencing large-scale coverage expansions.
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Acessibilidade aos Serviços de Saúde , Medicaid , Pobreza , Humanos , Medicaid/economia , Medicaid/estatística & dados numéricos , Estados Unidos , Acessibilidade aos Serviços de Saúde/economia , Acessibilidade aos Serviços de Saúde/estatística & dados numéricos , Adulto , Pessoa de Meia-Idade , Pobreza/economia , Feminino , Masculino , Adulto Jovem , Cobertura do Seguro/economia , Cobertura do Seguro/estatística & dados numéricos , Patient Protection and Affordable Care Act/economia , Reembolso de Seguro de Saúde/economia , Sistema de Vigilância de Fator de Risco ComportamentalRESUMO
Background: Increased availability of telehealth can improve access to health care. However, there is evidence of persistent disparities in telehealth usage, as well as among people from minoritized racial and ethnic groups and rural residents. The objective of our work was to explore the degree to which disparities in telehealth use for behavioral health (BH) and musculoskeletal (MSK) related services during the COVID-19 pandemic are explained by observed beneficiary- and area-level characteristics. Methods: Using North Carolina Medicaid claims data of Medicaid beneficiaries with BH or MSK conditions, we apply nonlinear regression-based decomposition analysis-based models developed by Kitagawa, Oaxaca, and Blinder to determine which observed variables are associated with racial, ethnic, and rural inequalities in telehealth usage. Results: In the BH cohort, we found statistically significant differences in telehealth usage by race in the adult population, and by race, Hispanic ethnicity, and rurality in the pediatric population. In the MSK cohort, we found significant inequities by Hispanic ethnicity and rurality among adults, and by race and rurality among children. Inequalities in telehealth use between groups were small, ranging from 0.7 percentage points between urban and rural adults with MSK conditions to 3.8 percentage points between white adults and people of color among those with BH conditions. Overall, we found that racial and ethnic inequalities in telehealth use are not well explained by the observed variables in our data. Rural disparities in telehealth use are better explained by observed variables, particularly area-level broadband internet use. Conclusions: For inequalities between rural and urban residents, our analysis provides observational evidence that infrastructure such as broadband internet access is an important driver of differences in telehealth use. For racial and ethnic inequalities, the pathways may be more complex and difficult to measure, particularly when relying on administrative data sources in place of more detailed data on individual-level socioeconomic factors.
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BACKGROUND: The shift from in-person to virtual visits, known as telehealth (TH), during the COVID-19 pandemic was a significant change for North Carolina (NC) Medicaid beneficiaries seeking treatment for musculoskeletal (MSK) conditions, as remote care for these conditions was previously unavailable. We used this policy change to investigate factors associated with TH uptake and whether TH availability mitigated disparities in access to care or affected emergency department (ED) visits among these beneficiaries. RESEARCH DESIGN: Using 2019-2021 NC Medicaid claims, we identified beneficiaries receiving treatment for MSK conditions before COVID-19 (March 2019-February 2020) and analyzed uptake of newly available TH during COVID-19 (April 2020-March 2021). We used descriptive analysis and Poisson generalized estimating equations to quantify TH uptake, factors associated with TH uptake, and the association with ED visits during COVID-19. RESULTS: Black and Hispanic beneficiaries were less likely to use TH compared with White and non-Hispanic counterparts (10%, P <0.001 and 20%, P =0.03, respectively). Adults eligible for Tailored Plans, specialized NC Medicaid plans for those with significant behavioral health needs or intellectual/developmental disabilities, were less likely to use TH [adjusted risk ratio (ARR):0.83, 95% CI (0.78, 0.87)]; youth eligible for Tailored Plans were more likely to use TH [ARR:1.28, 95% CI (1.16, 1.42)]. Lower county-level internet access was associated with lower TH use [ARR: 0.85, 95% CI (0.82, 0.99)]. No statistical difference in ED utilization was observed between TH users and non-users. CONCLUSIONS: TH has the potential to deliver convenient care to beneficiaries with MSK conditions who can access it. Further research and policy changes should explore and address underlying factors driving disparities and improve equitable access to care for this population.
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Crimean-Congo haemorrhagic fever virus (CCHFV) is a tick-borne virus causing Crimean-Congo haemorrhagic fever (CCHF), a disease reported to have a high fatality rate in numerous countries. The virus is geographically widespread due to its vector, and numerous wild and domestic animals can develop asymptomatic infection. Serological and limited molecular evidence of CCHFV has previously been reported in Camelus dromedarius (the dromedary, or one-humped camel) in the United Arab Emirates (UAE). In this study, 238 camel samples were screened for CCHFV RNA where 16 camel samples were positive for CCHFV by RT-PCR. Analysis of full-length CCHFV genome sequences revealed a novel lineage in camels from the UAE, and potential reassortment of the M segment of the genome.
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Camelus/virologia , Genoma Viral/genética , Vírus da Febre Hemorrágica da Crimeia-Congo/genética , Febre Hemorrágica da Crimeia/veterinária , Animais , Vírus da Febre Hemorrágica da Crimeia-Congo/isolamento & purificação , Febre Hemorrágica da Crimeia/sangue , Febre Hemorrágica da Crimeia/virologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Emirados Árabes UnidosRESUMO
Zika virus (ZIKV) cases have been detected across the United States (US) and locally acquired cases have been reported in Florida. Currently, there are no ZIKV screening guidelines and no data on the incidence among organ donors in the US. This retrospective study was conducted at Jackson Memorial-Miami Transplant Institute. Positive ZIKV tests in local deceased organ donors were investigated from 6/2016 to 1/2017. We evaluated demographics and risk factors for ZIKV infection among organ donors and transplant outcomes among recipients of donors with positive ZIKV testing. One hundred forty-two donors were analyzed. Ten percent had traveled to ZIKV-endemic countries and 19% had outdoor occupations. Only 3% had positive ZIKV IGG. None had a positive ZIKV IGM or PCR. ZIKV-positive donors were more likely to have traveled to ZIKV-endemic countries (50% vs. 9%, P = .05). The kidneys from a ZIKV-positive donor were transplanted in our hospital with no 6-month rejection, graft failure, or death in the recipients. Our study demonstrated a low prevalence of ZIKV among deceased donors in our community. Despite local ZIKV transmission, ZIKV was more common in donors who traveled to ZIKV-endemic countries. This cohort demonstrated excellent outcomes in recipients of ZIKV IGG-positive donors. However, larger studies are needed.
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Doadores de Sangue/provisão & distribuição , Seleção do Doador/normas , Programas de Rastreamento , Infecção por Zika virus/diagnóstico , Zika virus/isolamento & purificação , Adulto , Feminino , Florida/epidemiologia , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/genética , Estudos Retrospectivos , Zika virus/genética , Zika virus/imunologia , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/virologiaRESUMO
In May 2015 in United Arab Emirates, asymptomatic Middle East respiratory syndrome coronavirus infection was identified through active case finding in 2 men with exposure to infected dromedaries. Epidemiologic and virologic findings suggested zoonotic transmission. Genetic sequences for viruses from the men and camels were similar to those for viruses recently detected in other countries.
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Infecções Assintomáticas/epidemiologia , Infecções por Coronavirus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/patogenicidade , Adulto , Animais , Anticorpos Antivirais/análise , Anticorpos Antivirais/sangue , Camelus/sangue , Camelus/virologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/patologia , Humanos , Masculino , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Omã/epidemiologia , Emirados Árabes Unidos/epidemiologiaRESUMO
High seroprevalence of Middle East respiratory syndrome corona virus (MERS-CoV) in dromedary camels has been previously reported in United Arab Emirates (UAE). However, the molecular detection of the virus has never been reported before in UAE. Of the 7,803 nasal swabs tested in the epidemiological survey, MERS-CoV nucleic acid was detected by real-time PCR in a total of 126 (1.6 %) camels. Positive camels were detected at the borders with Saudi Arabia and Oman and in camels' slaughter houses. MERS-CoV partial sequences obtained from UAE camels were clustering with human- and camel-derived MERS-CoV sequences in the same geographic area. Results provide further evidence of MERS-CoV zoonosis.
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Camelus/virologia , Coronavírus da Síndrome Respiratória do Oriente Médio/isolamento & purificação , Animais , Análise por Conglomerados , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Epidemiologia Molecular , Dados de Sequência Molecular , Mucosa Nasal/virologia , Filogenia , Prevalência , RNA Viral/análise , RNA Viral/genética , Reação em Cadeia da Polimerase em Tempo Real , Análise de Sequência de DNA , Homologia de Sequência , Emirados Árabes Unidos/epidemiologia , Zoonoses/epidemiologia , Zoonoses/virologiaRESUMO
BACKGROUND: Poisoning in toddlers and infants is almost always unintentional due to their exploratory behavior, which is different from adults. The prevalence and background of childhood poisoning in Qatar is still unknown. The aim of this study is to explore the extent of childhood poisoning in Qatar and, specifically, to describe the frequency of poisoning as a cause of Accident & Emergency (A&E) admission, the demographic profile of affected patients, the circumstances leading to exposure, and the specific agents involved in poisoning among children under age 14 in our setting. METHODS: This study was a cross-sectional survey of children up to 14 years old utilizing retrospective data between October 2009 and October 2012. The data were collected from the childhood poisoning case registry and patient medical records at the Accident and Emergency (A&E) Unit of all the Hamad Medical Corporation hospitals. Pharmacists reviewed all the handwritten medical records. Data written on the data collection form were transferred into excel and later into SPSS version 21. The data were analyzed using frequencies and percentages, and a chi-square test was used for categorical variables. RESULTS: Out of 1179 registered poisoning cases listed in the registry, only 794 cases (67.3%) were usable and included in the final analysis. A&E admissions for unintentional poisoning for children accounted for 0.22% of all A&E admissions from 2009 to 12. The majority of poisoning cases happened among children between 1 and 5 years old (n = 704, 59.7%). Cases were more frequent among non-Qatari than Qatari children (39.4% vs. 28.5%). Most cases occurred in the living room (28.2%) and typically took place in the afternoon (29.2%). Analgesic and antipyretic medicines were the most common agents ingested by children (n = 194, 36.9%), specifically paracetamol (n = 140, 26.6%). CONCLUSIONS: Cases of unintentional poisoning are higher among children aged 1 to 5 years, males and non-Qatari. Most cases occurred in the living room and typically took place in the afternoon. The most common type of poison ingested by children was medicines, i.e., analgesics and antipyretics, specifically paracetamol.
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Serviço Hospitalar de Emergência/estatística & dados numéricos , Intoxicação/epidemiologia , Adolescente , Analgésicos/intoxicação , Antipiréticos/intoxicação , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Lactente , Masculino , Intoxicação/etiologia , Prevalência , Catar/epidemiologia , Estudos RetrospectivosRESUMO
Laboratory-acquired infections (LAIs) and accidental pathogen escape from laboratory settings (APELS) are major concerns for the community. A risk-based approach for pathogen research management within a standard biosafety management framework is recommended but is challenging due to reasons such as inconsistency in risk tolerance and perception. Here, we performed a scoping review using publicly available, peer-reviewed journal and media reports of LAIs and instances of APELS between 2000 and 2021. We identified LAIs in 309 individuals in 94 reports for 51 pathogens. Eight fatalities (2·6% of all LAIs) were caused by infection with Neisseria meningitidis (n=3, 37·5%), Yersinia pestis (n=2, 25%), Salmonella enterica serotype Typhimurium (S Typhimurium; n=1, 12·5%), or Ebola virus (n=1, 12·5%) or were due to bovine spongiform encephalopathy (n=1, 12·5%). The top five LAI pathogens were S Typhimurium (n=154, 49·8%), Salmonella enteritidis (n=21, 6·8%), vaccinia virus (n=13, 4·2%), Brucella spp (n=12, 3·9%), and Brucella melitensis (n=11, 3·6%). 16 APELS were reported, including those for Bacillus anthracis, SARS-CoV, and poliovirus (n=3 each, 18·8%); Brucella spp and foot and mouth disease virus (n=2 each, 12·5%); and variola virus, Burkholderia pseudomallei, and influenza virus H5N1 (n=1 each, 6·3%). Continual improvement in LAI and APELS management via their root cause analysis and thorough investigation of such incidents is essential to prevent future occurrences. The results are biased due to the reliance on publicly available information, which emphasises the need for formalised global LAIs and APELS reporting to better understand the frequency of and circumstances surrounding these incidents.
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Virus da Influenza A Subtipo H5N1 , Infecção Laboratorial , Yersinia pestis , Animais , Bovinos , Humanos , Salmonella enteritidis , Salmonella typhimuriumRESUMO
Introduction: Dromedary camels robustly withstand dehydration, and the rough desert environment but the adaptation mechanisms are not well understood. One of these mechanisms is that the dromedary camel increases its body temperature to reduce the process of evaporative cooling during the hot weather. Stress in general, has deleterious effects in the body. In this study, we sought to determine the effects of dehydration and rehydration on stress parameters in the dromedary camels and how it pacifies these effects. Methods: Nineteen male camels were randomly divided into control, dehydrated and rehydrated groups, and fed alfalfa hay ad-libitum. The dehydrated and rehydrated groups were water-restricted for 20 days after which the rehydrated camels were provided with water for 72 h. The control and dehydrated camels were slaughtered at day 20 from the start of experiment whereas the rehydrated group was killed 72 h later. Many biochemical, hematological histopathological parameters and gene analysis were performed in relevant tissues collected including blood, plasma, and tissues. Results and discussion: It was observed that severely dehydrated camels lost body weight, passed very hard feces, few drops of concentrated urine, and were slightly stressed as reflected behaviorally by loss of appetite. Physiologically, the stress of dehydration elicited modulation of plasma stress hormones for water preservation and energy supply. Our results showed significant increase in cortisol, norepinephrine and dopamine, and significant decrease in epinephrine and serotonin. The significant increase in malondialdehyde was accompanied with significant increase in antioxidants (glutathione, retinol, thiamin, tocopherol) to provide tissue protection from oxidative stress. The physiological blood changes observed during dehydration serve different purposes and were quickly restored to normality by rehydration. The dehydrated/rehydrated camels showed reduced hump size and serous atrophy of perirenal and epicardial fat. The latter changes were accompanied by significantly increased expression of genes encoding proteins for energy production (ANGPTL4, ACSBG1) from fat and significantly decreased expression of genes (THRSP; FADS 1&2) encoding proteins enhancing energy expenditure. This process is vital for camel survival in the desert. Dehydration induced no major effects in the vital organs. Only minor degenerative changes were observed in hepatic and renal cells, physiological cardiomyocyte hypertrophy in heart and follicular hyperplasia in splenic but lipidosis was not depicted in liver hepatocytes. Ketone bodies were not smelled in urine, sweat and breathing of dehydrated animals supporting the previous finding that the ß hydroxybutyrate dehydrogenase, a key enzyme in ketone body formation, is low in the camel liver and rumen. Rehydration restored most of blood and tissues to normal or near normal. In conclusion, camels are adapted to combat dehydration stress and anorexia by increasing anti-stressors and modulating genes involved in fat metabolism.
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Importance: After decades of rapid increase, Medicare per-beneficiary spending growth was historically low in the period leading up to the passage of the Affordable Care Act. In the years immediately following the legislation, Medicare expenditure growth slowed even further. Objective: To evaluate factors contributing to the slowdown in Medicare per-beneficiary spending growth. Design, Setting, and Participants: In this cross-sectional study, expected spending growth for 2012 to 2015 and 2016 to 2018 was predicted holding payment rates and population characteristics constant. By contrasting predicted and actual spending growth during these periods, the contribution of population vs payment factors to the Medicare spending slowdown was determined. Analyses included all Medicare fee-for-service beneficiaries aged 65 years and older, ranging from 30 to 35 million beneficiaries annually between 2007 and 2018. Data analyses were conducted from January 2018 to August 2018 and updated with new data in June 2021. Main Outcomes and Measures: The main outcome included annual growth in total per-beneficiary spending. The roles of payment rate changes and differences in the Medicare population over time were considered, including demographic characteristics and numbers of chronic conditions. Results: Between 2008 to 2011 and 2012 to 2015, the adjusted annual Medicare Parts A and B per-beneficiary spending growth rate declined from 3.3% to -0.1%. From 2016 to 2018, the mean annual Medicare spending growth rate rose relative to the previous period but remained lower than in the baseline period at 1.7% per year. This slowdown extended across all sectors within Parts A and B, except for physician-administered drugs offered under Part B. Changes in payment rates (including sequestration measures) and beneficiary characteristics explained 44% of the difference in overall per-beneficiary spending growth between 2007 to 2011 and 2012 to 2015, and 63% between 2007 to 2011 and 2016 to 2018. Conclusions and Relevance: In this cross-sectional study of trends in spending growth per Medicare beneficiary aged 65 years or older, results suggested that Medicare payment policy, including sector-specific payment rate changes and sequestration, will be a critical determinant of whether the Medicare spending growth slowdown persists.
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Medicare , Patient Protection and Affordable Care Act , Estados Unidos , Humanos , Idoso , Estudos Transversais , Planos de Pagamento por Serviço Prestado , Gastos em SaúdeRESUMO
BACKGROUND: Alternative Payment Models (APMs) piloted by the Centers for Medicare and Medicaid Services (CMS) such as ACO Realizing Equity, Access and Community Health (REACH) seek to improve care and quality of life among seriously ill populations (SIP). Days at Home (DAH) was proposed for use in this model to evaluate organizational performance. It is important to assess the utility and feasibility of person-centered outcomes measures, such as DAH, as CMS seeks to advance care models for seriously ill beneficiaries. We leverage existing Accountable Care Organization (ACO) contracts to evaluate the feasibility of ACO-level DAH measure and examine characteristics associated with ACOs with more DAH. METHODS: We calculated DAH for Medicare fee-for-service beneficiaries aged 68 and over who were retrospectively attributed to a Medicare ACO between 2014 and 2018 and met the seriously ill criteria. We then aggregated to the ACO level DAH for each ACO's seriously ill beneficiaries and risk-adjusted this aggregated measure. Finally, we evaluated associations between risk-adjusted DAH per person-year and ACO, beneficiary, and market characteristics. RESULTS: ACOs' seriously ill beneficiaries spent an average of 349.3 risk-adjusted DAH per person-year. Risk-adjusted ACO variation, defined as the interquartile range, was 4.21 days (IQR = 347.32-351.53). Beneficiaries of ACOs are composed of a less racially diverse beneficiary cohort, opting for two-sided risk models, and operating in markets with fewer hospital and Skilled Nursing Facility beds had more DAH. CONCLUSIONS: Substantial variation across ACOs in the DAH measure for seriously ill beneficiaries suggests the measure can differentiate between high and low performing provider groups. Key to the success of the metric is accurate risk adjustment to ensure providers have adequate resources to care for seriously ill beneficiaries. Organizational factors, such as the ACO size and level of risk, are strongly associated with more days at home.
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Organizações de Assistência Responsáveis , Idoso , Planos de Pagamento por Serviço Prestado , Humanos , Medicare , Qualidade de Vida , Estudos Retrospectivos , Estados UnidosRESUMO
A systematic investigation on the isotopic and elemental signature, for both stable and radioactive elements, and mineral contents was performed to examine the characteristics of subsurface formations collected at different depths between 3.962 km and 4.115 km around deep-laying coal seams located under the Marmarica plateau in Egypt. Concentrations of major and minor oxides (Na2O, MgO, Al2O3, SiO2, SO3, K2O, CaO, TiO2, MnO, ΣFeO + Fe2O3, SrO, ZrO2, and BaO) were determined by X-ray fluorescence and dependencies among these concentrations revealed the type and sort of the formations. Organic contents were determined by Fourier Transform infrared spectroscopy to investigate the variation of the CO/CC bonding ratio with depth. Rare earth elements (REE), specifically Y, Sc, La, Ce, Pr, Nd, Sm, Eu, Gd, Tb, Dy, Ho, Er, Tm, Yb, and Lu were determined by inductively coupled plasma mass spectrometry while actinoids were detected by the radioactive decay of its daughter nuclei. The results showed a high trapping of REE elements and actinoids in layers above the coal seams which indicates the occurrence of aqueous flow followed by possible sorption in these layers. The mobility of the fluid was investigated using the process radioactive decay series between Ra226 and Ac228 from one side and their daughters from the other side.
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Carvão Mineral , Metais Terras Raras , Carvão Mineral/análise , Isótopos/análise , Metais Terras Raras/análise , Minerais , Dióxido de SilícioRESUMO
Colistin is an antimicrobial agent that is used in resistant gram-negative infections. Its most common dose-limiting adverse effect is nephrotoxicity. The objective of our study was to explore the possible effects of each of taxifolin and dapagliflozin alone and in combination on colistin-induced nephrotoxicity in rats. Sixty male rats were randomized into six groups: Control; colistin; colistin + taxifolin; colistin + dapagliflozin; colistin + carboxymethyl cellulose (CMC) and colistin + taxifolin + dapagliflozin. Dapagliflozin, taxifolin, and CMC were given daily for 7 days, 4 hours before colistin injection. Kidney weight/body weight ratio and renal function tests were determined. Renal tissue nerve growth factor-ß (NGF-ß), transforming growth factor beta 1 (TGF-ß1), proinflammatory cytokines, nuclear factor (erythroid-derived 2)-like 2 (Nrf2), toll-like receptor 4 (TLR4), nuclear factor kappa B (NF-κB) p65, signal transducer and activator of transcription 3 (STAT3), oxidative stress parameters, beclin-1 and c-Jun NH2-terminal kinase (JNK) activities were measured. Kidneys were examined histopathologically and immunohistochemically. Taxifolin and/or dapagliflozin induced significant improvement in the renal functions and oxidative stress parameters with significant increase in tissue Nrf2, STAT3 and NGF-ß accompanied with significant decrease in kidney weight/body weight ratio, tissue proinflammatory cytokines, TGF-ß1, NF-κB (p65), TLR4, beclin-1 and JNK activities and improved the histopathological picture when compared to rats treated with colistin alone. This improvement was significant with taxifolin/dapagliflozin combination compared to rats treated with each of these agents alone. So, we concluded that the combined use of taxifolin and dapagliflozin may confer a therapeutic tool for attenuation of colistin-induced nephrotoxicity.
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Compostos Benzidrílicos/farmacologia , Colistina/toxicidade , Glucosídeos/farmacologia , Nefropatias/induzido quimicamente , Nefropatias/tratamento farmacológico , Quercetina/análogos & derivados , Animais , Antibacterianos/toxicidade , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/farmacologia , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Compostos Benzidrílicos/administração & dosagem , Combinação de Medicamentos , Regulação da Expressão Gênica/efeitos dos fármacos , Glucosídeos/administração & dosagem , MAP Quinase Quinase 4/genética , MAP Quinase Quinase 4/metabolismo , Masculino , Quercetina/administração & dosagem , Quercetina/farmacologia , Distribuição Aleatória , Ratos , Inibidores do Transportador 2 de Sódio-Glicose/administração & dosagem , Inibidores do Transportador 2 de Sódio-Glicose/farmacologiaRESUMO
A homozygous missense mutation, C566T, in the follicle stimulation hormone receptor (FSHR) gene has been linked to premature ovarian failure. The disease leads to infertility in a normal karyotype female with an elevated follicle stimulating hormone (FSH) and decreased serum estrogen level. Female mice carrying mutated FSHR gene, called follitropin receptor knockout (FORKO), display similar phenotype and are sterile because of a folliculogenesis block at a primary stage. We investigated the effects of bilateral intra-ovarian injection of an adenovirus expressing a normal copy of human FSHR on the reproductive system of 6-10 weeks female FORKO mice. Ad-LacZ was injected directly into each ovary of the control group. Animals were sacrificed at 2, 4, 8 and 12 weeks post-injection and tissues collected for evaluation. Treated mice showed estrogenic changes in daily vaginal smear whereas control animals remained fixated in the diestrus stage. Histological evaluation showed on average 26 +/- 4 follicles/ovary in treated group with 8 +/- 2 follicles at the antral stage compared with only 5 +/- 2 with zero follicles at antral stage in Ad-LacZ control mice. There was no significant change in serum level of progesterone, however, estrogen level increased 2-3-fold (P < 0.02) and FSH decreased by up to 50% (P < 0.04) in treated animals. FSHR mRNA was detected in the ovaries of the treated group. In conclusion, intra-ovarian injection of an adenovirus expressing human FSHR gene is able to restore FSH responsiveness and reinitiate ovarian folliculogenesis as well as resume estrogen production in female FORKO mice. Ad-LacZ injections indicate the absence of systemic viral dissemination or germ line transmission of adenovirus DNA to offspring.
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Terapia Genética , Insuficiência Ovariana Primária/genética , Insuficiência Ovariana Primária/terapia , Receptores do FSH/genética , Receptores do FSH/metabolismo , Adenoviridae/genética , Animais , Feminino , Vetores Genéticos/genética , Humanos , Camundongos , Camundongos Knockout , Reação em Cadeia da Polimerase Via Transcriptase ReversaRESUMO
BACKGROUND: Leukocyte adhesion molecules are important for migration of the inflammatory cells into sites of inflammation. Intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1) are members of the immunoglobulin superfamily that are expressed in normal kidney. Their expression is up-regulated in the renal tissue of patients with lupus nephritis (LN). OBJECTIVES: We evaluated whether changes in urinary levels of ICAM-1 and VCAM-1 reflect renal tissue damage in LN. We related the levels of these molecules to other laboratory findings, especially complement C3/C4 levels. We also tested the hypothesis that changes in urinary levels of ICAM-1 and VCAM-1 reflect the severity of renal tissue damage in LN. PATIENTS AND METHODS: This study included 30 systemic lupus erythematosus (SLE) patients with LN (16 with mild histological changes, i.e., with World Health Organization (WHO) class I and II LN, and 14 with advanced histological changes, i.e., class III, IV, and V LN) and 20 with SLE without nephritis. In addition, 20 healthy individuals of comparable age were included as a control group. The levels of urinary ICAM-1 and VCAM-1 were measured by enzyme-linked immunosorbent assay (ELISA) and related to the clinical, laboratory [rheumatoid factor(RF), antinuclear antibodies (ANA), anti-double-stranded DNA (anti-dsDNA), complements C3 and C4] and histological findings. RESULTS: Levels of urinary ICAM-1 and VCAM-l in LN patients with advanced histological changes (renal damage) were statistically significantly higher than those in other groups (LN patients with mild histological changes or SLE patients without nephritis and control group; p < 0.01). In contrast, serum levels of C3 and C4 in LN patients with advanced histological changes were significantly lower than those in other groups (p < 0.01). There was a significant negative correlation between the levels of urinary adhesion molecules and serum complement levels (p < 0.01). CONCLUSIONS: The significantly high urinary levels of the adhesion molecules in the LN group with advanced histological changes may reflect their renal tissue expression and therefore the severity of the nephritis. Renal tissue damage in these cases may be the result of transmigration of activated inflammatory cells, inducing serious tissue damage. The hypocomplementemia combined with increased urinary levels of adhesion molecules seems to be a useful biomarker of disease severity in LN.
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Molécula 1 de Adesão Intercelular/urina , Rim/imunologia , Nefrite Lúpica/urina , Molécula 1 de Adesão de Célula Vascular/urina , Adulto , Complemento C3/metabolismo , Complemento C4/metabolismo , Feminino , Humanos , Rim/patologia , Nefrite Lúpica/patologia , MasculinoRESUMO
BACKGROUND: Retinoid receptors (RRs), RAR-α and RXR-α, work as transcription factors that regulate cell growth, differentiation, survival, and death. Hepatic stellate cells (HSCs) store retinoid and release its RRs as lipid droplets upon their activation. PURPOSE: We test the hypothesis that loss of retinoid receptors RAR-α and RXR-α from HSCs is dependent on tissue factor (TF) during thioacetamide (TAA)-induced liver injury. METHODS: Liver toxicity markers, TF, fibrin, cleaved caspase-3, and cyclin D1 as well as histopathology were investigated. RESULTS: Increased TF, fibrin, cleaved caspase-3, and cyclin D1 protein expression is seen in zone of central vein after TAA injection compared with vehicle-treated mice. A strong downregulation of RAR-α and RXR-α is seen in TAA-induced liver injury. In addition, histopathological obliteration and pericentral expression of cleaved caspase 3 and cyclin D1 are observed after TAA injection compared with the normal vehicle-treated mice. No changes have been seen in TAA/TF-sense (SC) in whole parameters compared with TAA-treated animals. TAA/TF-antisense (AS)-treated mice show normal expression of all parameters and normal histopathological features when compared with the control mice. In conclusion, this study declares that the strong downregulation of RAR-α and RXR-α may cause liver injury and particularly activation of HSCs in TAA-induced toxicity. TF-AS treatment not only downregulates TF protein expression but also alleviates loss of liver RAR-α and RXR-α and suppresses the activated apoptosis signals in TAA-induced liver toxicity. Finally, TF and RAR-α/RXR-α are important regulatory molecules in TAA induced acute liver injury.
Assuntos
Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Oligonucleotídeos Antissenso/farmacologia , Tioacetamida/toxicidade , Tromboplastina/antagonistas & inibidores , Tromboplastina/metabolismo , Animais , Doença Hepática Induzida por Substâncias e Drogas/prevenção & controle , Masculino , Camundongos , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Receptor X Retinoide alfa/metabolismoRESUMO
Background: Camelpox is the most infectious and economically important disease of camelids that causes significant morbidity and mortality rates. Several live attenuated vaccines against Camelpox virus (CMLV) are produced worldwide by passaging field isolates in cell culture. Sequence of a high passage Saudi isolate of CMLV was previously found closely resembled Vaccinia virus (VACV). Aim: To determine whether other high cell culture passage CMLV isolates are genetically resemble VACV and further to explore the possible mechanism of the resemblance. Methods: We performed polymerase chain reaction and DNA sequence analysis of A-type inclusion body protein (ATIP), L1R, and open reading frame (ORF) 185 genes on different cell culture passage levels of a field isolate, two high passage vaccines, wild-type, and reference strains of CMLV. Results: We demonstrate that additional two high passage attenuated vaccine candidate from Sudan and UAE likewise contain sequences resembling VACV more than CMLV. Furthermore, sequence analysis of the ATIP gene of selected virus passages in cell culture revealed that the shift to VACV-like occurred between passage 11 and 20 and up to the 10th passage the genome still resembles wild-type virus. This observation was further confirmed by recombination analysis which indicated recombination events at ATIP and ORF185 genes occurred at higher passages. Conclusion: We confirmed that the cell culture passage CMLV turns to resemble VACV after cell culture passage and concluded that the resemblance may not be a result of contamination or misidentification as previously thought but could be due to recombination events that occurred during the passage process.
Assuntos
Camelus/virologia , Orthopoxvirus/imunologia , Infecções por Poxviridae/veterinária , Vacinas Atenuadas/genética , Vaccinia virus/genética , Animais , Técnicas de Cultura de Células/veterinária , Fases de Leitura Aberta/genética , Orthopoxvirus/genética , Reação em Cadeia da Polimerase/veterinária , Infecções por Poxviridae/prevenção & controle , Infecções por Poxviridae/virologia , Análise de Sequência de DNA/veterináriaRESUMO
This study was conducted to evaluate the use of Brucellergene skin test (BST) for the diagnosis of Brucellosis in camels (Camelus dromedarius) in comparison with Rose Bengal test (RBT) and competitive enzyme-linked immunosorbent assay (c-ELISA). A total of 68 apparently healthy adult dromedary camels of either gender from three different geographical locations of Abu Dhabi Emirate, United Arab Emirates (UAE), were included in the study. The skin test was applied on two shaved areas at the middle of the neck: one for the test and the other area was injected with normal saline as a control. Reading was done 72 h postinjection. Results were subjected to Bayesian analysis to assess the test performances in camels. The model estimated the following sensitivity and specificity median values: BST: Se = 70.72%, Sp = 98.82%; RBT: Se = 93.27%, Sp = 97.79%; and c-ELISA: Se = 94.78%, Sp = 98.48%. As the BST investigated in this study proved to be a highly specific test, we propose using it as a confirmatory test in camels particularly when the serological tests give doubtful results on individual animals.
Assuntos
Brucelose/veterinária , Camelus/microbiologia , Testes Cutâneos/veterinária , Animais , Brucelose/diagnóstico , Brucelose/microbiologia , Ensaio de Imunoadsorção Enzimática/veterinária , Rosa Bengala , Sensibilidade e Especificidade , Testes Sorológicos/veterinária , Testes Cutâneos/métodosRESUMO
Camelpox is a viral contagious disease of Old-World camelids sustained by Camelpox virus (CMLV). The disease is characterized by mild, local skin or severe systemic infections and may have a major economic impact due to significant losses in terms of morbidity and mortality, weight loss, and low milk yield. Prevention of camelpox is performed by vaccination. In this study, we investigated the composition of a CMLV-based, live-attenuated commercial vaccine using next-generation sequencing (NGS) technology. The results of this analysis revealed genomic sequences of Modified Vaccinia virus Ankara (MVA).