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The atmospheric concentration of methane has more than doubled since the start of the Industrial Revolution. Methane is the second-most-abundant greenhouse gas created by human activities and a major driver of climate change. This APS-Optica report provides a technical assessment of the current state of monitoring U.S. methane emissions from oil and gas operations, which accounts for roughly 30% of U.S. anthropogenic methane emissions. The report identifies current technological and policy gaps and makes recommendations for the federal government in three key areas: methane emissions detection, reliable and systematized data and models to support mitigation measures, and effective regulation.
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Poluentes Atmosféricos , Gases de Efeito Estufa , Gases de Efeito Estufa/análise , Humanos , Metano/análiseRESUMO
In response to an absence of studies among refugees and host communities accessing highly active antiretroviral therapy (HAART) in urban settings, our objective was to compare adherence and virological outcomes among clients attending a public clinic in Kuala Lumpur, Malaysia. A cross-sectional survey was conducted among adult clients (≥18 years). Data sources included a structured questionnaire that measured self-reported adherence, a pharmacy-based measure of HAART prescription refills over the previous 24 months, and HIV viral loads. The primary outcome was unsuppressed viral load (≥40 copies/mL). Among a sample of 153 refugees and 148 host community clients, refugees were younger (median age 35 [interquartile range, IQR 31, 39] vs 40 years [IQR 35, 48], p < 0.001), more likely to be female (36 vs 21 %, p = 0.004), and to have been on HAART for less time (61 [IQR 35, 108] vs 153 weeks [IQR 63, 298]; p < 0.001). Among all clients, similar proportions of refugee and host clients were <95 % adherent to pharmacy refills (26 vs 34 %, p = 0.15). When restricting to clients on treatment for ≥25 weeks, similar proportions from each group were not virologically suppressed (19 % of refugees vs 16 % of host clients, p = 0.54). Refugee status was not independently associated with the outcome (adjusted odds ratio, aOR = 1.28, 95 % CI 0.52, 3.14). Overall, the proportions of refugee and host community clients with unsuppressed viral loads and sub-optimal adherence were similar, supporting the idea that refugees in protracted asylum situations are able to sustain good treatment outcomes and should explicitly be included in the HIV strategic plans of host countries with a view to expanding access in accordance with national guidelines for HAART.
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Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/virologia , Cooperação do Paciente , Refugiados , Adolescente , Adulto , Contagem de Linfócito CD4 , Estudos Transversais , Emigração e Imigração , Feminino , Humanos , Malásia , Análise Multivariada , Fatores Socioeconômicos , Resultado do Tratamento , Carga Viral/efeitos dos fármacosRESUMO
There is a significant opportunity to expand the understanding of subcutaneous injection mechanics with an aim to increase injectable volume while controlling tissue strain and associated subject pain. Computational modeling can evaluate the mechanics of subcutaneous injections as a supplement to experimental, animal and clinical studies. The objectives of this study are to (1) develop a computational model for subcutaneous injection in tissue, (2) investigate the influence anisotropic tissue permeability has on bolus formation, and (3) explore the effects that injection flow rate and viscosity have on injection flow and tissue strain. Poroelastic models with subsurface flow were implemented in finite element software (COMSOL, ABAQUS). Pore pressure and injectate distribution showed excellent agreement with experimental results when evaluated at multiple injection rates (20 ml/hr, 120 ml/hr and 360 ml/hr). Including the anisotropy of tissue permeability causes the injectate to preferentially spread horizontally, similar to experimentally observed bolus distributions. Cases are presented to provide additional insight into injection mechanics, including variations on the delivery rate, the injection volume, viscosity and the thickness of the subcutaneous layer. The results support the use of computational modeling as a valid tool for understanding tissue strains and injectate distributions for large volume injections.
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Simulação por Computador , Permeabilidade , Pressão , Injeções Subcutâneas , Viscosidade , Anisotropia , Humanos , Análise de Elementos Finitos , Modelos Biológicos , Animais , Dinâmica não Linear , PorosidadeRESUMO
With the advancement of modern medicine and the prolonged survival of critically ill patients, unusual organisms are increasingly emerging. Initially found in the environment, these rare organisms started presenting as human pathogens, causing significant morbidity and mortality. Here, we present a rare case of disseminated Lodderomyces elongisporus fungemia and Pantoea dispersa bacteremia in a patient with parapneumonic effusion and ruptured liver abscess. This yeast was identified using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF). Although this organism has no antifungal breakpoint, the isolate shows low minimum inhibitory concentration (MIC) to a wide range of antifungals. The importance of effective communication between microbiologists and clinicians and early referral to the infectious disease team was also highlighted in this case for prompt treatment.
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Mucormycosis is a serious and often fatal fungal infection that is most commonly observed in immunocompromised individuals. The mortality rate of mucormycosis is high if left untreated, and successful treatment requires a combination of antifungal therapy, surgical intervention, and reversal of the underlying immunocompromised state. The choice of antifungal treatment is crucial and depends on several factors, including the safety profile of the drug, its spectrum of activity, and the species of fungus causing the infection. In this report, we describe a case of a patient who presented with mucormycosis and was successfully treated with a combination of antifungal therapy, surgical excision of affected tissue, and reversal of the underlying immunocompromised state. Our report underscores the importance of early recognition and aggressive treatment of mucormycosis to improve outcomes for affected patients.
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Endophthalmitis is an infection of the vitreous and/or aqueous humours, caused by bacteria or fungi, and can be either exogenous (resulting from trauma or intraocular procedures) or endogenous (hematogenous in origin). Although less common than exogenous endophthalmitis, endogenous endophthalmitis can have serious, vision-threatening consequences. Streptococcus pneumoniae is a rare cause of endogenous endophthalmitis and is associated with a poor prognosis. In this report, we present a rare case of pneumococcal endogenous endophthalmitis that led to a devastating outcome despite both medical and surgical interventions. Early systemic treatment and prompt identification of the primary source are crucial and potentially life-saving.
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In this study, we used imaging and proteomics to identify the presence of virus-associated cellular proteins that may play a role in respiratory syncytial virus (RSV) maturation. Fluorescence microscopy of virus-infected cells revealed the presence of virus-induced cytoplasmic inclusion bodies and mature virus particles, the latter appearing as virus filaments. In situ electron tomography suggested that the virus filaments were complex structures that were able to package multiple copies of the virus genome. The virus particles were purified, and the protein content was analyzed by one-dimensional nano-LC MS/MS. In addition to all the major virus structural proteins, 25 cellular proteins were also detected, including proteins associated with the cortical actin network, energy pathways, and heat shock proteins (HSP70, HSC70, and HSP90). Representative actin-associated proteins, HSC70, and HSP90 were selected for further biological validation. The presence of beta-actin, filamin-1, cofilin-1, HSC70, and HSP90 in the virus preparation was confirmed by immunoblotting using relevant antibodies. Immunofluorescence microscopy of infected cells stained with antibodies against relevant virus and cellular proteins confirmed the presence of these cellular proteins in the virus filaments and inclusion bodies. The relevance of HSP90 to virus infection was examined using the specific inhibitors 17-N-Allylamino-17-demethoxygeldanamycin. Although virus protein expression was largely unaffected by these drugs, we noted that the formation of virus particles was inhibited, and virus transmission was impaired, suggesting an important role for HSP90 in virus maturation. This study highlights the utility of proteomics in facilitating both our understanding of the role that cellular proteins play during RSV maturation and, by extrapolation, the identification of new potential targets for antiviral therapy.
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Proteínas de Choque Térmico HSP90/química , Vírus Sinciciais Respiratórios/fisiologia , Vírion/fisiologia , Montagem de Vírus/fisiologia , Western Blotting , Eletroforese em Gel de Poliacrilamida , Proteínas de Choque Térmico HSP90/fisiologia , Imunoprecipitação , RNA Interferente Pequeno , Vírion/químicaRESUMO
Cryptococcosis is a systemic fungal infection caused by Cryptococcus neoformans or Cryptococcus gattii. Cryptococcus causes a wide range of diseases, ranging from asymptomatic pulmonary lesions to disseminated disease involving the central nervous system, particularly meningoencephalitis. C. gattii infection has rarely been reported in Malaysia. We present a case of C. gattii meningitis with pulmonary cryptococcosis complicated by immune reconstitution inflammatory syndrome in an apparently immunocompetent person with no prior travel history.
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Rhodococcus hoagii is a well-known zoonotic disease, especially in foals. Its occurrence in humans is uncommon and usually occurs in immunocompromised patients. We present a case of Rhodococcus hoagii infection resulting in necrotizing pneumonia in a patient with advanced retroviral disease who had defaulted treatment. Effective treatment of Rhodococcus hoagii infection requires a combination of antibiotics. We also highlighted the importance of effective communication between clinicians and microbiologists so that prompt treatment can be initiated to improve patient outcomes.
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Pneumonia Necrosante , Rhodococcus equi , Animais , Humanos , Cavalos , Pneumonia Necrosante/tratamento farmacológico , Antibacterianos/uso terapêuticoRESUMO
Enterococcus hirae infection accounts for about 1% of all enterococcal infections. This number is likely to be underestimated because of inadequate identification. Human infection due to E. hirae is rarely reported. We present the case of a young woman with diabetes mellitus who developed symptoms of pyelonephritis and diabetic ketoacidosis. Renal computed tomography scan revealed the presence of subcapsular perinephric collection and renal abscesses. Her blood culture yielded E. hirae. Our patient was successfully treated with antimicrobials based on the susceptibility result. To our knowledge, this is the first reported case of perinephric collection and renal abscesses associated with E. hirae bacteremia.
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Infective endocarditis can result in potentially fatal complications such as heart failure, systemic embolization, mycotic aneurysm and neurological complications. Staphylococci and streptococci are the most common causative agents of infective endocarditis, with Streptococcus gordonii being a rare cause. We present a case of infective endocarditis in a young patient who presented with an acute abdomen 2 months after being diagnosed with cerebrovascular accident. An abdominal computed tomography revealed superior mesenteric artery thrombosis, and infarct in the right kidney and spleen as a result of systemic septic embolism. Echocardiography showed numerous vegetations at the aortic and mitral valves. Infective endocarditis was diagnosed based on echocardiographic findings and positive blood cultures for S. gordonii. He was treated with intravenous benzylpenicillin and was also referred for surgical intervention.
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Cystic nephroma (CN) and mixed epithelial and stromal tumor (MEST) are rare benign renal neoplasms that have overlapping clinical and morphologic features, including predominance in middle-aged women, variably cystic architecture, eosinophilic cells, and hobnail cells lining the cysts and ovarian-type stroma. The aim of this study was to analyze and compare the histologic features and immunohistochemical profile of these tumors. We studied 34 cases from 5 large academic institutions. Twenty tumors were diagnosed as CNs, 18 in women and 2 in men, their age ranged from 24 to 63 (mean 48; median 50) years. Fourteen tumors were diagnosed as MESTs, all in women, their age ranged from 26 to 84 (mean 52; median 51) years. Histologically, all tumors were well-circumscribed except for one MEST. The stromal/epithelial ratio was approximately 2.3 in MESTs versus 0.3 in CNs; cellular ovarian-type stroma composed 45% of the stroma in MESTs and 12% of the stroma of CNs. Stromal hyalinization was prominent in both. Five MESTs showed stromal luteinization. In the epithelial component, the relative amount of large cysts, medium to small cysts, and phyllodes-type glands was: 65%/25%/10% in CNs versus 25%/40%/35% in MESTs. The epithelial component ranged from flat to cuboidal to hobnail cells in both types of tumors. No significant atypia of either component was seen, although the epithelial cells showed reactive changes. Immunohistochemical stains for estrogen receptors and progesterone receptors showed 62% and 85% positivity in the stromal component of MESTs versus 19% and 40% in CNs. CD10 positivity was seen in 77% of MESTs versus 50% of CNs, calretinin was seen in 69% of MESTs versus 41% of CNs, and inhibin in 42% of MESTs versus 36% of CNs, although the staining was focal. Follow-up in both categories of tumors (mean 3.2 y, median 3 y for CNs and mean 2.5 y, median of 2 y for MESTs) showed no evidence of recurrence or metastases in keeping with their benign nature. This study highlights the remarkable similarity between CN and MEST in sex predilection, age distribution, and morphologic attributes of both the epithelial and stromal components and immunohistochemical profile albeit with variation in individual categories with higher prevalence of stromal to epithelial ratio, prominent ovarian stroma, smaller cysts with phyllodes glands pattern and stromal luteinization being more common in MEST; and large cysts, thin septae and low stromal to epithelial ratio in CN. The presence of ovarian-type stroma and müllerian related immunohistochemical markers raises the possibility that these tumors may originate from müllerian remnants misplaced during embryogenesis. On the basis of detailed morphologic analysis of this series of CN and MEST, we propose a unifying term of "renal epithelial and stromal tumor" (REST) to encompass the spectrum of findings observed in these tumors at least until new molecular studies can prove or disprove this challenging hypothesis.
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Neoplasias Renais/classificação , Neoplasias Renais/patologia , Neoplasias Epiteliais e Glandulares/classificação , Neoplasias Epiteliais e Glandulares/patologia , Nefroma Mesoblástico/classificação , Nefroma Mesoblástico/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Imuno-Histoquímica , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Neoplasias Epiteliais e Glandulares/metabolismo , Nefroma Mesoblástico/metabolismo , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo , Células Estromais/metabolismo , Células Estromais/patologiaRESUMO
BACKGROUND: Inconsistent literature evidence suggests that sociodemographic, economic, and system- and patient-related factors are associated with clinic attendance among the HIV-positive population receiving antiretroviral therapy (ART) around the world. We examined the factors that predict outpatient clinic attendance among a cohort of HIV-positive patients initiating ART in Selangor, Malaysia. PATIENTS AND METHODS: This cross-sectional study analyzed secondary data on outpatient clinic attendance and sociodemographic, economic, psychosocial, and patient-related factors among 242 adult Malaysian patients initiating ART in Selangor, Malaysia. Study cohort was enrolled in a parent randomized controlled trial (RCT) in Hospital Sungai Buloh Malaysia between January and December 2014, during which peer counseling, medication, and clinic appointment reminders were provided to the intervention group through short message service (SMS) and telephone calls for 24 consecutive weeks. Data on outpatient clinic attendance were extracted from the hospital electronic medical records system, while other patient-level data were extracted from pre-validated Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires in which primary data were collected. Outpatient clinic attendance was categorized into binary outcome - regular attendee and defaulter categories - based on the number of missed scheduled outpatient clinic appointments within a 6-month period. Multivariate regression models were fitted to examine predictors of outpatient clinic attendance using SPSS version 22 and R software. RESULTS: A total of 224 (93%) patients who completed 6-month assessment were included in the model. Out of those, 42 (18.7%) defaulted scheduled clinic attendance at least once. Missed appointments were significantly more prevalent among females (n=10, 37.0%), rural residents (n=10, 38.5%), and bisexual respondents (n=8, 47.1%). Multivariate binary logistic regression analysis showed that Indian ethnicity (adjusted odds ratio [AOR] =0.235; 95% CI [0.063-0.869]; P=0.030) and heterosexual orientation (AOR =4.199; 95% CI [1.040-16.957]; P=0.044) were significant predictors of outpatient clinic attendance among HIV-positive patients receiving ART in Malaysia. CONCLUSION: Ethnicity and sexual orientation of Malaysian patients may play a significant role in their level of adherence to scheduled clinic appointments. These factors should be considered during collaborative adherence strategy planning at ART initiation.
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BACKGROUND: Adherence to treatment remains the cornerstone of long term viral suppression and successful treatment outcomes among patients receiving Antiretroviral Therapy (ART). OBJECTIVE(S): Evaluate the effectiveness of mobile phone reminders and peer counseling in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia. METHODS: A single-blind, parallel group RCT conducted in Hospital Sungai Buloh, Malaysia in which 242 adult Malaysian patients were randomized to intervention or control groups. Intervention consisted of a reminder module delivered through SMS and telephone call reminders by trained research assistants for 24 consecutive weeks (starting from date of ART initiation), in addition to adherence counseling at every clinic visit. The length of intended follow up for each patient was 6 months. Data on adherence behavior of patients was collected using specialized, pre-validated Adult AIDS Clinical Trial Group (AACTG) adherence questionnaires. Data on weight, clinical symptoms, CD4 count and viral load tests were also collected. Data was analyzed using SPSS version 22 and R software. Repeated measures ANOVA, Friedman's ANOVA and Multivariate regression models were used to evaluate efficacy of the intervention. RESULTS: The response rate after 6 months follow up was 93%. There were no significant differences at baseline in gender, employment status, income distribution and residential location of respondents between the intervention and control group. After 6 months follow up, the mean adherence was significantly higher in the intervention group (95.7; 95% CI: 94.39-96.97) as compared to the control group (87.5; 95% CI: 86.14-88.81). The proportion of respondents who had Good (>95%) adherence was significantly higher in the intervention group (92.2%) compared to the control group (54.6%). A significantly lower frequency in missed appointments (14.0% vs 35.5%) (p = 0.001), lower viral load (p = 0.001), higher rise in CD4 count (p = 0.017), lower incidence of tuberculosis (p = 0.001) and OIs (p = 0.001) at 6 months follow up, was observed among patients in the intervention group. CONCLUSION: Mobile phone reminders (SMS and telephone call reminders) and peer counseling are effective in improving adherence and treatment outcomes among HIV positive patients on ART in Malaysia. These findings may be of potential benefit for collaborative adherence planning between patients and health care providers at ART commencement.
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Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Terapia Antirretroviral de Alta Atividade/métodos , Telefone Celular , Aconselhamento a Distância/métodos , Cooperação do Paciente , Grupo Associado , Adolescente , Adulto , Feminino , Humanos , Malásia , Masculino , Pessoa de Meia-Idade , Telemedicina/métodos , Resultado do TratamentoRESUMO
Medication adherence remains a critical link between the prescribed ART regimen and treatment outcome. Several factors may influence adherence behavior. This cross-sectional study aimed to highlight socioeconomic predictors of adherence behavior among a cohort of 242 adult Malaysian patients receiving antiretroviral therapy in Hospital Sungai Buloh, Malaysia, where they were enrolled in a parent study (single-blinded randomized controlled trial) between January and December 2014. Statistical analysis of secondary data on adherence behavior and sociodemographic characteristics of the patients revealed mean age of 33.4 years and ranged from 18 to 64 years; 88.8% were males. A total of 224 (93%) patients who completed 6 months' adherence assessment were included in the model. Of these, 135 (60.3%) achieved optimal adherence. Multivariate binary logistic regression analysis revealed that patient's income and ethnicity were significant predictors of adherence behavior. This may be valuable for targeted programmatic interventions to further enhance successful treatment outcomes among the target population.
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Fármacos Anti-HIV/uso terapêutico , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/psicologia , Adolescente , Adulto , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Malásia , Masculino , Adesão à Medicação/estatística & dados numéricos , Pessoa de Meia-Idade , Fatores Socioeconômicos , Adulto JovemRESUMO
Mucinous tubular and spindle cell carcinoma, a rare, recently described distinctive subtype of renal cell carcinoma, may have some morphologic similarities to the more common papillary renal cell carcinoma, particularly the basophilic (type 1) tumors with prominent solid growth pattern. Tumor circumscription, compact tubular architecture, focal papillations, mucin production and foam cells (features seen in both papillary renal cell carcinoma and mucinous tubular and spindle cell carcinoma), as well as spindle cell morphology, have resulted in some cases sent to us in consultation with a question of possible sarcomatoid papillary renal cell carcinoma. In this study, tissue microarrays with triplicate samples each from 27 mucinous tubular and spindle cell carcinomas and 20 papillary renal cell carcinomas were created to simulate experience in renal biopsy specimens. From immunohistochemistry (IHC) data, published in the contemporary literature, a panel consisting of alpha-methylacyl-CoA racemase (AMACR), cytokeratin 7 (CK7), epithelial membrane antigen (EMA), renal cell carcinoma marker (RCC Ma), CD10, high molecular weight cytokeratin (HMWK), and c-kit was designed to test its utility in differential diagnosis. The immunoreactivity in mucinous tubular and spindle cell carcinoma was AMACR 93%, CK7 81%, EMA 95%, RCC Ma 7%, CD10 15%, HMWK 15%, and c-kit 5% and in papillary renal cell carcinoma was AMACR 95%, CK7 65%, EMA 88%, RCC Ma 25%, CD10 80%, HWMK 15%, and c-kit 18%. This largest study to date on IHC of mucinous tubular and spindle cell carcinoma dispels the specificity of AMACR for papillary renal cell carcinoma among the RCC subtypes. The histogenesis of mucinous tubular and spindle cell carcinoma from the distal nephron continues to be debatable, as our study showed the expression of the proximal convoluted tubule-related marker AMACR among these tumors. Thus, in tumors with predominant compact tubular growth and focal papillary architectures, careful attention to the presence of a low-grade spindle cell population may be helpful in the distinction of mucinous tubular and spindle cell carcinoma, as the key immunohistochemical stains for papillary renal cell carcinoma are also expressed in this subtype of renal cell carcinoma.