ATR-FTIR Spectroscopy for the Assessment of Biochemical Changes in Skin Due to Cutaneous Squamous Cell Carcinoma

Nonmelanoma skin cancers represent 95% of cutaneous neoplasms. Among them, squamous cell carcinoma (SCC) is the more aggressive form and shows a pattern of possible metastatic profile. in this work, we used Fourier transform infrared spectroscopy (FTIR) spectroscopy to assess the biochemical changes in normal skin caused by squamous cell carcinoma induced by multi-stage chemical carcinogenesis in mice. Changes in the absorption intensities and shifts were observed in the vibrational modes associated to proteins, indicating changes in secondary conformation in the neoplastic tissue. Hierarchical cluster analysis was performed to evaluate the potential of the technique to differentiate the spectra of neoplastic and normal skin tissue, so that the accuracy obtained for this classification was 86.4%. in this sense, attenuated total reflection (ATR)-FTIR spectroscopy provides a useful tool to complement histopathological analysis in the clinical routine for the diagnosis of cutaneous squamous cell carcinoma.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto Nacional de Ciencia e Tecnologia Fotonica (INCT)Produtividade em Pesquisa (PQ)IPEN CNEN SP, Ctr Lasers & Applicat, Inst Pesquisas Energet & Nucl, BR-05508000 São Paulo, SP, BrazilUniv São Paulo, Sch Dent, BR-05508000 São Paulo, SP, BrazilUniversidade Federal de São Paulo, ICT, BR-1223128 Sao Jose Dos Campos, SP, BrazilUniversidade Federal de São Paulo, ICT, BR-1223128 Sao Jose Dos Campos, SP, BrazilFAPESP: 05/51689-2CAPES: 071/2013-88881.068505/2014-01Instituto Nacional de Ciencia e Tecnologia Fotonica (INCT): 573.916/2008-0Produtividade em Pesquisa (PQ): 312397/2013-5Web of Scienc

Overrepresentation of Injection Drug Use Route of Infection Among Human Immunodeficiency Virus Long-term Nonprogressors: A Nationwide, Retrospective Cohort Study in China, 1989-2016.

BackgroundWhy some persons living with human immunodeficiency virus (HIV) (PLWH) progress quickly and others remain "healthy" for a decade or more without treatment remains a fundamental question of HIV pathology. We aimed to assess the epidemiological characteristics of HIV long-term nonprogressors (LTNPs) based on a cohort of PLWH in China observed between 1989 and 2016.MethodsWe conducted a nationwide, retrospective cohort study among Chinese PLWH with HIV diagnosed before 1 January 2008. Records were extracted from China's national HIV/AIDS database on 30 June 2016. LTNPs were defined as those with AIDS-free, antiretroviral therapy-naive survival, with CD4 cell counts consistently ≥500/μL for ≥8 years after diagnosis. Prevalence was calculated, characteristics were described, and determinants were assessed by means of logistic regression. Potential sources of bias were also investigated.ResultsOur cohort included 89 201 participants, of whom 1749 (2.0%) were categorized as LTNPs. The injection drug use (IDU) route of infection was reported by 70.7% of LTNPs, compared with only 37.1% of non-LTNPs. The odds of LTNP status were greater among those infected via IDU (adjusted odds ratio [95% confidence interval], 2.28 [1.94-2.68]) and with HIV diagnosed in settings with large populations of persons who inject drugs (1.75 [1.51-2.02] for detention centers, 1.61 [1.39-1.87] for Yunnan, 1.94 [1.62-2.31] for Guangdong, and 2.90 [2.09-4.02] for Xinjiang).ConclusionsOverrepresentation of the IDU route of infection among LTNPs is a surprising finding worthy of further study, and this newly defined cohort may be particularly well suited to exploration of the molecular biological mechanisms underlying HIV long-term nonprogression

Clinical Features, Treatment, and Outcome of HIV-Associated Immune Thrombocytopenia in the HAART Era

The characteristics of HIV-associated ITP were documented prior to the HAART era, and the optimal treatment beyond HAART is unknown. We performed a review of patients with HIV-associated ITP and at least one platelet count <20 × 109/L since January 1996. Of 5290 patients in the BC Centre for Excellence in HIV/AIDS database, 31 (0.6%) had an ITP diagnosis and platelet count <20 × 109/L. Initial ITP treatment included IVIG, n = 12; steroids, n = 10; anti-RhD, n = 8; HAART, n = 3. Sixteen patients achieved response and nine patients achieved complete response according to the International Working Group criteria. Median time to response was 14 days. Platelet response was not significantly associated with treatment received, but complete response was lower in patients with a history of injection drug use. Complications of ITP treatment occurred in two patients and there were four unrelated deaths. At a median followup of 48 months, 22 patients (71%) required secondary ITP treatment. This is to our knowledge the largest series of severe HIV-associated ITP reported in the HAART era. Although most patients achieved a safe platelet count with primary ITP treatment, nearly all required retreatment for ITP recurrence. New approaches to the treatment of severe ITP in this population are needed

In vitro screening of cytotoxic activity of euphol from Euphorbia tirucalli on a large panel of human cancer-derived cell lines

A large number of classic antineoplastic agents are derived from plants. Euphorbia tirucalli L. (Euphorbiaceae) is a subtropical and tropical plant, used in Brazilian folk medicine against many diseases, including cancer, yet little is known about its true anticancer properties. The present study evaluated the antitumor effect of the tetracyclic triterpene alcohol, euphol, the main constituent of E. tirucalli in a panel of 73 human cancer lines from 15 tumor types. The biological effect of euphol in pancreatic cells was also assessed. The combination index was further used to explore euphol interactions with standard drugs. Euphol showed a cytotoxicity effect against several cancer cell lines (IC50 range, 1.41-38.89 µM), particularly in esophageal squamous cell (11.08 µM) and pancreatic carcinoma cells (6.84 µM), followed by prostate, melanoma, and colon cancer. Cytotoxicity effects were seen in all cancer cell lines, with more than half deemed highly sensitive. Euphol inhibited proliferation, motility and colony formation in pancreatic cancer cells. Importantly, euphol exhibited synergistic interactions with gemcitabine and paclitaxel in pancreatic and esophageal cell lines, respectively. To the best of our knowledge, this study constitutes the largest in vitro screening of euphol efficacy on cancer cell lines and revealed its in vitro anti-cancer properties, particularly in pancreatic and esophageal cell lines, suggesting that euphol, either as a single agent or in combination with conventional chemotherapy, is a potential anti-cancer drug.Amazônia Fitomedicamentos Ltda. (grant no. FITO 05/2012) and Barretos Cancer Hospital, all from Brazilinfo:eu-repo/semantics/publishedVersio

DO FORNECIMENTO DOS SERVIÇOS PÚBLICOS PELO ESTADO

O presente artigo tem a finalidade de demonstrar o que são serviços públicos e a importância dessas atividades para toda a coletividade, sendo regido tal instituto pelo regime de Direito Público, instrumento este que atende o interesse público. Também é verificado como se dá a prestação dos serviços públicos e se os mesmos são realizados com qualidade ou não para os administrados. E por fim, quais seriam as soluções dos problemas da prestação dos serviços públicos e quais seriam as condições necessárias para que o Estado possa funcionar como fornecedor desses serviços. Palavras-chave: Serviço Público, Coletividade, Regime de Direito Público, Qualidade

Modulatory antimicrobial activity of Piper arboretum extracts (Zingiberaceae)

The side effects of certain antibiotics have been a recent dilemma in the medical arena. Due this fact, the necessity of natural product discovery could provide important indications against several pharmacological targets and combat many infectious agents. Piper arboreum Aub. (Piperaceae) has been used by Brazilian traditional communities against several illnesses including rheumatism, bronchitis, sexually transmitted diseases and complaints of the urinary tract. Medicinal plants are a source of several remedies used in clinical practice to combat microbial infections. In this study, ethanol extract and fractions of Piper arboreum leaves were used to assay antimicrobial and modulatory activity. The minimum inhibitory concentration (MIC) was determined using microdilution method of ethanol extract and fractions from the leaves of P. arboreum ranging between 8 and 1024 mgmL–1. The capacity of these natural products to enhance the activity of antibiotic and antifungal drugs was also assayed. In these tests, natural products were combined with drugs. The natural products assayed did not demonstrate any clinically relevant antimicrobial activity (MIC ³ 1024 mg mL–1). However, the modulation of antibiotic activity assay observed a synergistic activity of natural products combined with antifungal (such as nystatin and amphotericin B) and antibiotic drugs (such as amikacin, gentamicin and kanamycin). According to these results, these natural products can be an interesting alternative not only to combat infectious diseases caused by bacteria or fungi, but also to combat enhanced resistance of microorganisms to antibiotic and antifungal drugs

New segregates from the Neotropical genus Stryphnodendron (Leguminosae, Caesalpinioideae, mimosoid clade)

Non-monophyly is a prominent issue in mimosoid legumes, even in some of the less speciose genera such as the neotropical genus Stryphnodendron. This genus includes 35 species occurring from Nicaragua to Southern Brazil mostly in humid forests and savannas. Previous taxonomic studies of Stryphnodendron have highlighted morphologically distinct groups within the genus, recognized by differences on leaves (number of pinnae and size of leaflets), inflorescences (a simple or compound thyrse), and fruit types (legume, nucoid legume or follicle). Recent phylogenetic analyses have confirmed the non-monophyly of Stryphnodendron, supporting the recognition of three independent and morphologically well-delimited genera. Here we re-circumscribe Stryphnodendron and propose the two new genera Gwilymia and Naiadendron. In addition, we also provide an updated taxonomic account of the closely related genus Microlobius, including the proposal of a lectotype for the single species in the genus

Application and Validation of Case-Finding Algorithms for Identifying Individuals with Human Immunodeficiency Virus from Administrative Data in British Columbia, Canada

Objective To define a population-level cohort of individuals infected with the human immunodeficiency virus (HIV) in the province of British Columbia from available registries and administrative datasets using a validated case-finding algorithm. Methods Individuals were identified for possible cohort inclusion from the BC Centre for Excellence in HIV/AIDS (CfE) drug treatment program (antiretroviral therapy) and laboratory testing datasets (plasma viral load (pVL) and CD4 diagnostic test results), the BC Centre for Disease Control (CDC) provincial HIV surveillance database (positive HIV tests), as well as databases held by the BC Ministry of Health (MoH); the Discharge Abstract Database (hospitalizations), the Medical Services Plan (physician billing) and PharmaNet databases (additional HIV-related medications). A validated case-finding algorithm was applied to distinguish true HIV cases from those likely to have been misclassified. The sensitivity of the algorithms was assessed as the proportion of confirmed cases (those with records in the CfE, CDC and MoH databases) positively identified by each algorithm. A priori hypotheses were generated and tested to verify excluded cases. Results A total of 25,673 individuals were identified as having at least one HIV-related health record. Among 9,454 unconfirmed cases, the selected case-finding algorithm identified 849 individuals believed to be HIV-positive. The sensitivity of this algorithm among confirmed cases was 88%. Those excluded from the cohort were more likely to be female (44.4% vs. 22.5%; p&lt;0.01), had a lower mortality rate (2.18 per 100 person years (100PY) vs. 3.14/100PY; p&lt;0.01), and had lower median rates of health service utilization (days of medications dispensed: 9745/100PY vs. 10266/100PY; p&lt;0.01; days of inpatient care: 29/100PY vs. 98/100PY; p&lt;0.01; physician billings: 602/100PY vs. 2,056/100PY; p&lt;0.01). Conclusions The application of validated case-finding algorithms and subsequent hypothesis testing provided a strong framework for defining a population-level cohort of HIV infected people in BC using administrative databases

Apathy and functional disability in behavioral variant frontotemporal dementia

Background Behavioral variant frontotemporal dementia (bvFTD) has profound consequences on patients and their families. In this multicenter study, we investigated the contribution of cognitive and neuropsychiatric factors to everyday function at different levels of overall functional impairment. Methods In a retrospective cross-sectional study, 109 patients with bvFTD from 4 specialist frontotemporal dementia centers (Australia, England, India, and Brazil) were included. The measures administered evaluated everyday function (Disability Assessment for Dementia [DAD]), dementia staging (Clinical Dementia Rating [CDR]), general cognition (Addenbrooke’s Cognitive Examination–revised [ACE-R]), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). Patients were then subdivided according to functional impairment on the DAD into mild, moderate, severe, and very severe subgroups. Three separate multiple linear regression analyses were run, where (1) total DAD, (2) basic activities of daily living (BADL), and (3) instrumental activities of daily living (IADL) scores were dependent variables; ACE-R total score and selected NPI domains (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) were used as independent variables. Age, sex, education, and country of origin were controlled for in the analyses. Results Cognitive deficits were similar across the mild, moderate, and severe subgroups but significantly worse in the very severe subgroup. NPI domain scores (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) did not differ across the DAD subgroups. In the multiple regression analyses, a model including ACE-R and NPI apathy explained 32.5% of the variance for total DAD scores. For IADL, 35.6% of the variance was explained by the ACE-R only. No model emerged for BADL scores. Conclusions Cognitive deficits and apathy are key contributors to functional disability in bvFTD but factors underlying impairment in BADLs remain unclear. Treatments targeting reduction of disability need to address apathy and cognitive impairment to ensure greater efficacy, especially in regards to IADLs