Seroprevalence of antibodies against SARS-CoV-2 in the school community in Campo Grande, state of Mato Grosso do Sul, Brazil, October 2021-November 2022.

Introduction: With the reopening of schools during the coronavirus disease 2019 (COVID-19) pandemic, it was imperative to understand the role of students and education professionals in the spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this paper, we determined the seroprevalence of the SARS-CoV-2 anti-nucleocapsid antibodies in the school community in Campo Grande, the capital and most populous city of the state of Mato Grosso do Sul (Brazil) and evaluated its association with sex, school level, and school type. Materials and methods: The survey was carried out in 20 public and private schools in the urban region of Campo Grande using the TR DPP® COVID-19 immunoglobulin M/immunoglobulin G (IgM/IgG) kit from the Immunobiological Technology Institute (Bio-Manguinhos, Rio de Janeiro, Brazil). Testing was carried out in three periods: from October to December 2021; from March to July 2022; and from August to November 2022. The participants were students aged 6-17 years enrolled in primary or secondary schools and professionals of different ages and roles. Results: During the first testing period, 162 participants were seropositive for the IgM and/or IgG anti-nucleocapsid SARS-CoV-2 antibodies, with an estimated seroprevalence of 19.6% using Bayesian multilevel regression. In the second period, 251 participants were seropositive (estimated seroprevalence, 34.6%), while in the third period, 393 participants were seroconverted (estimated seroprevalence, 56.7%). In 2022, there was an increase in the seroconversion rate compared to that in 2021. The most frequently described acute manifestations in the three periods were fever, headache, sore throat, and runny nose. In terms of the demographic profile, there was no predominance of seropositivity between the sexes, although women represented approximately 70% of the study population. There were also no differences between students and school staff. Discussion: The results made it possible to evaluate the extent of SARS-CoV-2 transmission in the school community through immunity developed against the virus, in addition to providing information about COVID-19 symptoms in children, adolescents, and adults.

A descriptive study on isoniazid resistance-associated mutations, clustering and treatment outcomes of drug-resistant tuberculosis in a high burden country.

PURPOSE: To describe katG and inhA mutations, clinical characteristics, treatment outcomes and clustering of drug-resistant tuberculosis (TB) in the State of São Paulo, southeast Brazil. METHODS: Mycobacterium tuberculosis isolates from patients diagnosed with drug-resistant TB were screened for mutations in katG and inhA genes by line probe assay and Sanger sequencing, and typed by IS6110-restriction fragment-length polymorphism for clustering assessment. Clinical, epidemiological and demographic data were obtained from surveillance information systems for TB. RESULTS: Among the 298 isolates studied, 127 (42.6%) were isoniazid-monoresistant, 36 (12.1%) polydrug-resistant, 93 (31.2%) MDR, 16 (5.4%) pre-extensively drug-resistant (pre-XDR), 9 (3%) extensively drug-resistant (XDR) and 17 (5.7%) susceptible after isoniazid retesting. The frequency of katG 315 mutations alone was higher in MDR isolates, while inhA promoter mutations alone were more common in isoniazid-monoresistant isolates. Twenty-six isolates phenotypically resistant to isoniazid had no mutations either in katG or inhA genes. The isolates with inhA mutations were found more frequently in clusters (75%) when compared to the isolates with katG 315 mutations (59.8%, p = 0.04). In our population, being 35-64 years old, presenting MDR-, pre-XDR- or XDR-TB and being a retreatment case were associated with unfavourable TB treatment outcomes. CONCLUSION: We found that katG and inhA mutations were not equally distributed between isoniazid-monoresistant and MDR isolates. In our population, clustering was higher for isolates with inhA mutations. Finally, unfavourable TB outcomes were associated with specific factors.

A FIOCRUZ Mato Grosso do Sul e o enfrentamento à covid-19 / FIOCRUZ Mato Grosso do Sul and the fight against covid-19

O E-book apresentado é um compilado interdisciplinar de trabalhos escritos por pesquisadores dedicados e comprometidos com a sociedade e com os diversos entes governamentais do estado na linha de frente do combate ao Coronavírus. Os dois primeiros capítulos são dedicados a Inquéritos sorológicos levados a cabo nos municípios de Campo Grande e Corumbá, fruto dos trabalhos de coleta, testagem e genotipagem realizados pela equipe de pesquisadores e técnicos da FIOCRUZ-MS. A coordenação de educação da FIOCRUZ-MS também teve papel fundamental neste esforço conjunto, o livro segue apresentando alguns dos trabalhos de pesquisa realizados por estes pós-graduandos. Mantendo o foco ainda nos efeitos da pandemia sobre os profissionais da saúde, o capítulo sétimo trata exatamente dos Transtornos mentais comuns e insegurança dos profissionais da saúde em tempos de pandemia. Finalizando este livro trazemos uma reflexão sobre Sindemia da covid-19 e sofrimento social entre os povos indígenas no Mato Grosso do Sul.

Impaired expression of serine/arginine protein kinase 2 (SRPK2) affects melanoma progression.

Melanoma is one of the most aggressive tumors, and its lethality is associated with the ability of malignant cells to migrate and invade surrounding tissues to colonize distant organs and to generate widespread metastasis. The serine/arginine protein kinases 1 and 2 (SRPK1 and SRPK2) are classically related to the control of pre-mRNA splicing through SR protein phosphorylation and have been found overexpressed in many types of cancer, including melanoma. Previously, we have demonstrated that the pharmacological inhibition of SRPKs impairs pulmonary colonization of metastatic melanoma in mice. As the used compounds could target at least both SRPK1 and SRPK2, here we sought to obtain additional clues regarding the involvement of these paralogs in melanoma progression. We analyzed single-cell RNA sequencing data of melanoma patient cohorts and found that SRPK2 expression in melanoma cells is associated with poor prognosis. Consistently, CRISPR-Cas9 genome targeting of SRPK2, but not SRPK1, impaired actin polymerization dynamics as well as the proliferative and invasive capacity of B16F10 cells in vitro. In further in vivo experiments, genetic targeting of SRPK2, but not SRPK1, reduced tumor progression in both subcutaneous and caudal vein melanoma induction models. Taken together, these findings suggest different functional roles for SRPK1/2 in metastatic melanoma and highlight the relevance of pursuing selective pharmacological inhibitors of SRPK2.

Immunomodulatory activity of trifluoromethyl arylamides derived from the SRPK inhibitor SRPIN340 and their potential use as vaccine adjuvant.

The serine/arginine-rich protein kinases (SRPK) specifically phosphorylate their substrates at RS-rich dipeptides, which are abundantly found in SR splicing factors. SRPK are classically known for their ability to affect the splicing and expression of gene isoforms commonly implicated in cancer and diseases associated with infectious processes. Non-splicing functions have also been attributed to SRPK, which highlight their functional plasticity and relevance as therapeutic targets for pharmacological intervention. In this sense, different SRPK inhibitors have been developed, such as the well-known SRPIN340 and its derivatives, with anticancer and antiviral activities. Here we evaluated the potential immunomodulatory activity of SRPIN340 and three trifluoromethyl arylamide derivatives. In in vitro analysis with RAW 264.7 macrophages and primary splenocytes, all the compounds modulated the expression of immune response mediators and antigen-presentation molecules related to a tendency for M2 macrophage polarization. Immunization experiments were carried out in mice to evaluate their potential as vaccine immunostimulants. When administrated alone, the compounds altered the expression of immune factors at the injection site and did not produce macroscopic or microscopic local reactions. In addition, when prepared as an adjuvant with inactivated EHV-1 antigens, all the compounds increased the anti-EHV-1 neutralizing antibody titers, a change that is consistent with an increased Th2 response. These findings demonstrate that SRPIN340 and its derivatives exhibit a noticeable capacity to modulate innate and adaptative immune cells, disclosing their potential to be used as vaccine adjuvants or in immunotherapies.

Prospecção de novos candidatos a fármacos antituberculose: uma abordagem in vitro / Prospecting new candidates for antituberculosis drugs: an in vitro approach

A tuberculose (TB) é uma doença infecciosa causada pelo Mycobacterium tuberculosis que apresenta alta morbidade e mortalidade. Atualmente, a tuberculose afeta 9,9 milhões de pessoas em todo o mundo e é responsável por cerca de 1,3 milhões de mortes, sendo um sério problema de Saúde Pública global. O tratamento da TB é composto por uma associação de fármacos e dura seis meses. A frequência de doentes infectados com isolados resistentes aos fármacos de primeira linha, principalmente os isolados multirresistentes, é uma ameaça mundial que caracteriza um importante problema de saúde pública no controle da TB em vários países. Existem poucos medicamentos para o tratamento da TB muti-resistente e com base nesta problemática o presente estudo visou a avaliação do potencial farmacológico in vitro de fármacos aprovados, utilizando a abordagem de reposicionamento de fármacos. A partir de uma triagem in vitro de 89 fármacos, foram selecionados os que apresentaram atividade antituberculose para a avaliação da concentração inibitória mínima, os fármacos foram avaliados em exposição a 23 isolados do complexo Mycobacterium tuberculosis e a cepa ATCC H37 RV 27294 in vitro utilizando o ensaio de resazurina. Além disso, foram realizados ensaios de citotoxicidade contra células de mamíferos NCTC L929 em cultura, determinando-se os Índices de Seletividade in vitro. Dentre os 89 fármacos testados, quatro (amiodarona, flunarizina, ivermectina e pentamidina) apresentaram atividade antituberculose a 10 µM. A Concentração Inibitória Mínima (CIM) 90% da amiodarona resultou em 5-10 µM, flunarizina 10 µM, ivermectina 0,15 ­ 10 µM e pentamidina 1,25-10 µM. Os índices de seletividade observados para a amiodarona foram de 4,21 ­ 8,43, flunarizina >20, ivermectina 1,17 ­ 78,47 e pentamidina 14,40 ­ 115,2. Com base na atividade e citotoxicidade da amiodarona, foi realizado um ensaio fluorimétrico utilizando Sytox Green para avaliar a permeabilidade de membrana plasmática do complexo M. tuberculosis na presença deste fármaco. Foi observado que a amiodarona não alterou a permeabilidade da membrana plasmática do Complexo M. tuberculosis, tendo seu mecanismo de ação letal por outra via.

Correlating genetic mutations with isoniazid phenotypic levels of resistance in Mycobacterium tuberculosis isolates from patients with drug-resistant tuberculosis in a high burden setting.

We analysed mutations in katG, inhA and rpoB genes, and isoniazid phenotypic resistance levels in Mycobacterium tuberculosis isolates from drug-resistant TB patients from São Paulo state, Brazil. Isolates resistant to the critical concentration of isoniazid in MGIT (0.1 µg/mL) were screened for mutations in katG 315 codon, inhA promoter region and rpoB RRDR by MTBDRplus assay and subjected to determination of isoniazid resistance levels by MGIT 960. Discordances were resolved by Sanger sequencing. Among the 203 isolates studied, 109 (54%) were isoniazid-monoresistant, 47 (23%) MDR, 29 (14%) polydrug-resistant, 12 (6%) pre-XDR and 6 (3%) XDR. MTBDRplus detected isoniazid mutations in 75% (153/203) of the isolates. Sequencing of the entire katG and inhA genes revealed mutations in 18/50 wild-type isolates by MTBDRplus (10 with novel mutations), resulting in a total of 32/203 (16%) isolates with no mutations detected. 81/83 (98%) isolates with katG 315 mutations alone had intermediate resistance. Of the 66 isolates with inhA C-15T mutation alone, 51 (77%) showed low-level, 14 (21%) intermediate and 1 (2%) high-level resistance. 5/6 (83%) isolates with mutations in both katG and inhA had high-level resistance. Inferred mutations corresponded to 22% (16/73) of all mutations found in rpoB. Mutations detected in katG regions other than codon 315 in this study might be potential new isoniazid resistance markers and could explain phenotypic resistance in some isolates without katG and inhA classic mutations. In our setting, 16% of isoniazid-resistant isolates, some with high-level resistance, presented no mutations either in katG or inhA.

Proteomic Analysis Reveals a Predominant NFE2L2 (NRF2) Signature in Canonical Pathway and Upstream Regulator Analysis of Leishmania-Infected Macrophages.

CBA mice macrophages (MØ) control infection by Leishmania major and are susceptive to Leishmania amazonensis, suggesting that both parasite species induce distinct responses that play important roles in infection outcome. To evaluate the MØ responses to infection arising from these two Leishmania species, a proteomic study using a Multidimensional Protein Identification Technology (MudPIT) approach with liquid chromatography tandem mass spectrometry (LC-MS/MS) was carried out on CBA mice bone-marrow MØ (BMMØ). Following SEQUEST analysis, which revealed 2,838 proteins detected in BMMØ, data mining approach found six proteins significantly associated with the tested conditions. To investigate their biological significance, enrichment analysis was performed using Ingenuity Pathway Analysis (IPA). A three steps IPA approach revealed 4 Canonical Pathways (CP) and 7 Upstream Transcriptional Factors (UTFs) strongly associated with the infection process. NRF2 signatures were present in both CPs and UTFs pathways. Proteins involved in iron metabolism, such as heme oxigenase 1 (HO-1) and ferritin besides sequestosome (SQSMT1 or p62) were found in the NRF2 CPs and the NRF2 UTFs. Differences in the involvement of iron metabolism pathway in Leishmania infection was revealed by the presence of HO-1 and ferritin. Noteworty, HO-1 was strongly associated with L. amazonensis infection, while ferritin was regulated by both species. As expected, higher HO-1 and p62 expressions were validated in L. amazonensis-infected BMMØ, in addition to decreased expression of ferritin and nitric oxide production. Moreover, BMMØ incubated with L. amazonensis LPG also expressed higher levels of HO-1 in comparison to those stimulated with L. major LPG. In addition, L. amazonensis-induced uptake of holoTf was higher than that induced by L. major in BMMØ, and holoTf was also detected at higher levels in vacuoles induced by L. amazonensis. Taken together, these findings indicate that NRF2 pathway activation and increased HO-1 production, together with higher levels of holoTf uptake, may promote permissiveness to L. amazonensis infection. In this context, differences in protein signatures triggered in the host by L. amazonensis and L. major infection could drive the outcomes in distinct clinical forms of leishmaniasis.

HIV cure: global overview of bNAbs' patents and related scientific publications.

INTRODUCTION: This article provides a global overview of patent deposits for broadly neutralizing antibodies (bNAbs), which have emerged as a key strategy for HIV cure and future HIV vaccines. Scientific and technological barriers to the discovery of an effective HIV vaccine in the last 40 years have raised concerns on the potential for relevant advances in this area. Nevertheless, recent breakthrough studies have identified novel immune pathways for new innovative HIV vaccine and HIV cure strategies. AREAS COVERED: In our patent study, we have identified in a global scale, in the last decade, a sharp increase in the number of bNAbs' patent deposits related to HIV prevention and treatment strategies, reaching 90 bNAbs in 2017, protected by 184 different patent deposits. Refining our patent search to the different stages of bNAbs' development has also allowed us to identify 12 of them already at clinical stage of research (VRC01, 10E8, 3BNC117, 10-1074, 2G12, 2F5, KD-247, 4E10, PG9, PGDM1400, PGT121, and VRC07). We describe these recent breakthroughs and discuss the prospects and limitations of these novel strategies. EXPERT OPINION: Our results indicate the intellectual property outcomes of a scientific revolution in this field, expressing innovative modifications in antibodies to increase their potency and half-life, which have resulted in extremely potent antibodies that could provide novel preventive and therapeutic HIV strategies.

Case study of patents related to captopril, Squibb's first blockbuster.

INTRODUCTION: Arterial hypertension affects over one billion people around the world, making the prevention and treatment of this disease vital. Despite the efforts made to develop new antihypertensive drugs, few new therapies have become available. Angiotensin-converting enzyme (ACE) inhibitors have heralded major steps forward in the treatment of arterial hypertension and cardiovascular diseases since the first compound of this class, captopril, was approved for clinical use in 1981. Areas covered: In this review, the authors investigated the patent documents that cite the priority patent for captopril, Squibb's first blockbuster, or any other patent from its patent family. The documents were classified into the following: new compounds, new compositions, treatment, process (preparation of a compound), use of a compound, and process for the preparation of an intermediate. Therefore, the readers can identify potential innovations in the field. Expert opinion: The pharmaceutical sector has attempted to provide significant technological developments on anti-hypertensive drugs based on the patenting of captopril, including the development of new compositions further comprising an ACE inhibitor and other antihypertensive agent, along with dual action compounds, novel molecules with dual activity. The target is to find a new agent with better blood pressure-lowering efficacy, improved safety and good tolerability profile.

Implementation of baby boomer hepatitis C screening and linking to care in gastroenterology practices: a multi-center pilot study.

BACKGROUND: Estimates suggest that only 20 % of HCV-infected patients have been identified and <10 % treated. However, baby boomers (1945-1965) are identified as having a higher prevalence of HCV which has led the Centers for Disease Control and Prevention to make screening recommendations. The aim of this study was to implement the CDC's screening recommendations in the unique setting of gastroenterology practices in patients previously unscreened for HCV. METHODS: After obtaining patient informed consent, demographics, clinical and health-related quality of life (HRQOL) data were collected. A blood sample was screened for HCV antibody (HCV AB) using the OraQuick HCV Rapid Antibody Test. HCV AB-positive patients were tested for presence of HCV RNA and, if HCV RNA positive, patients underwent treatment discussions. RESULTS: We screened 2,000 individuals in 5 gastroenterology centers located close to large metropolitan areas on the East Coast (3 Northeast, 1 Mid-Atlantic and 1 Southeast). Of the screened population, 10 individuals (0.5 %) were HCV AB-positive. HCV RNA testing was performed in 90 % (9/10) of HCV AB-positive individuals. Of those, 44.4 % (4/9) were HCV RNA-positive, and all 4 (100 %) were linked to caregiver. Compared to HCV AB negative subjects, HCV AB-positive individuals tended to be black (20.0 vs. 5.2 %, p = 0.09) and reported significantly higher rates of depression: 60.0 vs. 21.5 %, p = 0.009. These individuals also reported a significantly lower HRQOL citing having more fatigue, poorer concentration, and a decreased level of energy (p < 0.05). DISCUSSION: Although the prevalence of HCV AB-positive was low in previously unscreened subjects screened in the gastroenterology centers, the linkage to care was very high. The sample of patients used in this study may be biased, so further studies are needed to assess the effectiveness of the CDC screening recommendations. CONCLUSION: Implementation of the Baby Boomer Screening for HCV requires identifying screening environement with high prevalence of HCV+ individuals as well as an efficient process of linking them to care.

Nanoparticles applied to antineoplastic agents: a patent landscape.

Recently, research in the field of cancer nanotechnology has made notable progress, and, with the fast development of nanomaterials, new treatment strategies using nanoparticles are being explored that have the potential to overcome existing problems. The present review focuses on patenting as a key indicator of trends in nanoparticles with applications in the treatment of cancer. The impact of cancer on health and the use of nanoparticles are briefly described. Next, a survey of patents filed in the last 14 years is presented, the patents granted in the last four years are identified, and the focus areas of the main applicants are analyzed. The mix of targets identified for patented nanoparticles systems suggests that polymers and proteins are the main focus of the innovative efforts in this field.

Distribuição de massa molar em um biorreator com membrana para tratamento de efluente de laticínios / Molecular weight distribution in a membrane bioreactor for dairy effluent treatment

Os biorreatores com membrana (BRM) apresentam-se como um dos processos mais promissores para tratamento de águas residuárias com elevada carga orgânica, como os efluentes de laticínios, propiciando a geração de um efluente com elevada qualidade e adequado ao reuso direto ou após tratamento terciário. O objetivo desse trabalho foi avaliar o uso de BRM para tratamento de efluente de indústria de laticínios e utilizar a distribuição de massa molar da alimentação, do permeado e da fração solúvel do lodo como ferramenta para a investigação dos mecanismos de remoção dos poluentes no sistema. O BRM se mostrou um sistema viável para o tratamento do efluente em questão, apresentando eficiências de remoção de demanda química de oxigênio (DQO) e cor aparente de 98 e 99%, respectivamente. Através da distribuição de massa molar foi possível observar a alta capacidade de biodegradação e a estabilidade proporcionada pelo BRM, já que, mesmo em situações de alterações constantes nas características da alimentação, o líquido reacional sempre apresentou baixas concentrações de poluentes. Ressalta-se também a importância da membrana no sistema, uma vez que, além de permitir a retenção completa de biomassa e a operação com idades de lodo e concentração de sólidos suspensos maiores, pode proporcionar ainda a retenção de compostos que não foram biodegradados, contribuindo para a geração de um efluente tratado com alta qualidade.

The membrane bioreactor (MBR) is one of the most promising processes for the treatment of high organic load wastewaters, as dairy effluent, providing the generation of an effluent with high quality, which could be reuse directly or after tertiary treatment. The aim of this study was to evaluate a MBR to treat effluent from the dairy industry and to use molecular weight distribution of the feed, permeate and the soluble fraction of the sludge as a tool for investigating the mechanisms of pollutants removal in the system. The MBR has proven to be a viable system for the treatment of the effluent in question, with removal efficiencies of chemical oxidation demand (COD) and color of 98 and 99% respectively. Through the molar weight distribution it was possible to observe the high biodegradation capacity and stability provided by the MBR, as even in situations of constant change in feed characteristics, the mixed liquid always showed low concentrations of pollutants. It is also highlighted the importance of the membrane in the system, which, besides allowing the complete retention of biomass and operation with high solids retention time and suspended solids concentration, it can provide the retention of compounds which were not biodegraded, contributing to the generation a treated effluent with high quality.

Trends in nanopharmaceutical patents.

Investment in nanotechnology is now a given constant by governments, research centers and companies in both more developed countries and emerging markets. Due to their characteristics, such as high stability, ability to enable antigen identification on specific cells in the human body and controlling the release of drugs and, therefore, improving therapies, nanoparticles have been the subject of research and patent applications in the pharmaceutical field. According to the Organization for Economic Co-operation and Development (OCDE), patent data can be used as a source of information in order to measure science and technology activities. Thereby, this paper presents an analysis based on patent documents related to nanotechnology in the pharmaceutical sector. As a result, the analysis of patents demonstrate primarily that nanobiotechnology attracts high levels of R&D investments, including nanoparticle-based chemotherapeutic agents/drugs, monoclonal antibody nanoparticle complexes and their role in drug delivery or contrast agents with non-toxic effects.

Primary biliary cirrhosis is more severe in overweight patients.

GOALS: We sought to determine whether features of metabolic syndrome (MS) and histologic features of nonalcoholic steatohepatitis (NASH) are associated with increased fibrosis in patients with primary biliary cirrhosis (PBC). BACKGROUNDS: PBC is a chronic, progressive cholestatic disease. MS is strongly associated with NASH and fibrosis progression in some liver diseases. STUDY: Patients with PBC seen consecutively at the University of Miami between 1985 and 2008 who had antimitochondrial antibody positivity and a liver biopsy performed at this center at the time of diagnosis were identified. Demographics, clinical features, and biochemical parameters were collected. All liver biopsies were reviewed by a single blinded pathologist for features of NASH, PBC, and fibrosis. The impact of NASH and features of MS on liver biopsy findings were analyzed. RESULTS: Forty-nine patients [median age 51 (34 to 78) years, 98% females] were enrolled. Higher degree of steatosis, severe inflammatory grade, and severe biliary duct damage were each associated with advanced fibrosis (P<0.0001). Regarding MS, only overweight status [body mass index (BMI) ≥ 25] was associated with nonalcoholic fatty liver activity score (NAS) ≥ 5 (P<0.0001), biliary duct damage (P<0.0001), and advanced fibrosis (71% vs. 32%, P=0.007). Patients with NAS ≥ 5 had more severe fibrosis (14/15, 96% vs. 11/34, 44%; P=0.0001) and more severe biliary duct damage (13/15, 87% vs. 3/34, 9%; P=<0.0001). CONCLUSIONS: NASH and BMI ≥ 25 are associated with severe biliary duct damage and fibrosis in patients with PBC. BMI could become a useful noninvasive tool to predict advanced fibrosis in PBC.

Prevalence and indicators of portal hypertension in patients with nonalcoholic fatty liver disease.

BACKGROUND & AIMS: Little is known about the prevalence and severity of portal hypertension in patients with nonalcoholic fatty liver disease (NAFLD). We investigated the prevalence and noninvasive predictors of portal hypertension in patients with NAFLD. METHODS: Signs of portal hypertension, including esophageal varices, splenomegaly, portosystemic encephalopathy, and ascites, were investigated in 354 patients with NAFLD. RESULTS: One hundred patients had portal hypertension at the time of NAFLD diagnosis (28.2%), 88 of these patients had septal fibrosis or cirrhosis (88%). Fibrosis stage correlated with presence (r = 0.41, P < .0001) and number of findings (r = 0.48, P = .006) of portal hypertension. Of the 204 patients with no or mild fibrosis (stages, 0-2), 12 patients had portal hypertension (6%); they had a significantly higher grade of steatosis, based on biopsy analysis, compared with the 192 patients without portal hypertension (94%). Thrombocytopenia, hyperbilirubinemia, cirrhosis, and obesity were associated independently with portal hypertension. Esophageal varices were found in 57 of the 128 patients undergoing endoscopic screening (44.5%) and were associated independently with thrombocytopenia, type 2 diabetes, and splenomegaly. CONCLUSIONS: Signs of portal hypertension were present in 25% of patients at the time of diagnosis of NAFLD; most had advanced fibrosis or cirrhosis. Portal hypertension can occur in a small proportion of patients with mild or no fibrosis and is associated with the extent of steatosis. Features of advanced liver disease and insulin resistance might identify patients with NAFLD and portal hypertension, and those expected to derive the most benefit from endoscopic screening for esophageal varices.

Trends in nanotechnology patents applied to the health sector.

The aim of the article is to present a method for identifying trends in patent applications for nanotechnology applied to the health sector around the world, based on the International Patent Classification. This classification divides the sector into: dental care, drugs, diagnostic kits, and medical apparatus & medical care. The Derwent database was mined for patent documents using nanotechnology terms associated with the IPC subclasses from the health subsectors. The number of patents was found to be rising, led by the United States, particularly universities and R centers. In the dental care subsector, nanotechnology was found to be used in composite material for manufacturing dental appliances. In drugs, the focus is on the use of nanoparticulate compositions comprising agents that are useful for a variety of diseases. In diagnostic kits, nanostructures have been patented that are capable of detecting target analytes. Meanwhile, in medical apparatus & medical care, patent applications have been made for nanocapsules and/or nanocomposite materials inserted in devices and guide catheters. A study was also made of patents in Brazil, where the same assignees and the same country (United States) as in the survey of global patents were found to be the leading patent applicants / holders.