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Abstract Background Increasing evidence suggests that culturally and linguistically responsive programs may improve substance abuse treatment outcomes among Latinos. However, little is known about whether individual practices or culturally and linguistically responsive contexts support efforts by first-time Latino clients to successfully complete mandated treatment. Methods We analyzed client and program data from publicly funded treatment programs contracted through the criminal justice system in California. A sample of 5,150 first-time Latino clients nested within 48 treatment programs was analyzed using multilevel logistic regressions. Results Outpatient treatment, homelessness, and a high frequency of drug use at intake were associated with decreased odds of treatment completion among Latinos. Programs that routinely offered a culturally and linguistically responsive practice—namely, Spanish-language translation—were associated with increased odds of completion of mandated treatment. Conclusions These preliminary findings suggest that concrete practices such as offering Spanish translation improve treatment adherence within a population that is at high risk of treatment dropout.

Abstract Introduction Short PLUNC1 (SPLUNC1) is the founding member of a family of proteins (PLUNCS) expressed in the upper respiratory tract and oral cavity, which may function in host defence. It is one of the most highly expressed genes in the upper airways and the protein has been detected in sputum and nasal secretions. The biology of the PLUNC family is poorly understood but in keeping with the putative function of the protein as an immune defence protein, a number of RNA and protein studies have indicated that SPLUNC1 is increased in inflammatory/infectious conditions such as Cystic Fibrosis (CF), COPD and allergic rhinitis. Methods We used immunohistochemistry to localise SPLUNC1 in lung tissue from patients with CF and a range of other lung diseases. We used a range of additional markers for distinct cell types to try to establish the exact site of secretion of SPLUNC1. We have complemented these studies with a molecular analysis of SPLUNC1 gene expression in primary human lung cell cultures and isolated inflammatory cell populations. Results In CF, expression of SPLUNC1 is significantly elevated in diseased airways and positive staining was noted in some of the inflammatory infiltrates. The epithelium of small airways of CF lung exhibit significantly increased SPLUNC1 staining compared to similar sized airways in non-CF lungs where staining is absent. Strong staining was also seen in mucous plugs in the airways, these included many inflammatory cells. No alveolar epithelial staining was noted in CF tissue. Airway epithelial staining did not co-localise with MUC5AC suggesting that the protein was not produced by goblet cells. Using serial sections stained with neutrophil elastase and CD68 we could not demonstrate co-localisation of SPLUNC1 with either neutrophils or macrophages/monocytes, indicating that these cells were not a source of SPLUNC1 in the airways of CF lungs. No change in staining pattern was noted in the small airways or lung parenchyma of other lung diseases studied including, COPD, emphysema or pneumonia where significant NE and CD68 staining was noted. Cultures of primary tracheobronchial epithelial cells were analysed by RT-PCR and showed that pro-inflammatory mediators did not induce expression of SPLUNC1. We have also shown that SPLUNC1 gene expression was not seen in isolated human mononuclear cells, macrophages or neutrophils. Conclusion These studies show that SPLUNC1 is specifically and significantly increased in the small airways of lungs from patients with CF. They further suggest that it is the airway epithelium that is responsible for the increased levels of SPLUNC1 in CF and not inflammatory cells; this could be a defensive response to the infectious component of the disease.

Abstract Background The Whey Acidic Protein domain is an evolutionarily conserved motif found in a number of proteins, the best studied of which are antiproteinases involved in the innate immune defence of multiple epithelia. We recently characterised the WFDC2 gene which encodes a two WAP domain-containing protein, initially suggested as a marker for epididymis, and showed that it is highly expressed in the lung and salivary gland. The precise location of WFDC2 protein in these sites has not been described. Methods We used immunohistochemistry to localise WFDC2 in normal tissues of the respiratory tract, naso- and oropharynx, as well as in chronically inflamed lung from Cystic Fibrosis and a range of pulmonary carcinomas. We have complemented these studies with molecular analysis of WFDC2 gene expression in primary human lung cell cultures. Results WFDC2 is expressed in some epithelial cells of the upper airways as well as in mucous cells and ducts of submucosal glands. No staining was seen in peripheral lung. Intense staining is found in major salivary glands and in minor glands of the nose, sinuses, posterior tongue and tonsil. Studies with the related protein Secretory Leukocyte Protease Inhibitor (SLPI) show that although both proteins are expressed in similar tissues, the precise cellular localisation differs. Significant increases in expression and localisation of WFDC2 are seen in patients with Cystic Fibrosis. SLPI expression was greatly reduced in the same samples. In cultures of tracheobronchial epithelial cells, expression of WFDC2 and SLPI are differentially regulated during differentiation yet WFDC2 is not induced by pro-inflammatory mediators. The majority of adenocarcinomas stain with WFDC2 whilst a significant minority of squamous, small cell and large cell carcinomas exhibit focal staining. There is no clear association with tumour grade. Conclusion We believe that these studies support the hypothesis that WFDC2 may be a component of the innate immune defences of the lung, nasal and oral cavities and suggest that WFDC2 functions in concert with related WAP domain containing proteins in epithelial host defence. We also suggest that WFDC2 re-expression in lung carcinomas may prove to be associated with tumour type and should be studied in further detail.

Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications., Significance: To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM. This article is featured in Selected Articles from This Issue, p. 897., (©2024 American Association for Cancer Research.)

This paper reports the development of a near-infrared spectroscopy (NIRS) calibration procedure for the determination of sodium and potassium content in cured ham samples. Sliced samples of hams treated with different salts in different percentages were included in the study. Calibration models developed using partial least squares regression were cross-validated and predictive models were tested using the samples of cured ham with low sodium content. The results showed that the developed NIRS procedure is capable of directly measuring the potassium content of packaged dry-cured ham slices with low sodium content with a fitting accuracy of 91.44%, and that it can indirectly determine the sodium content by applying a correction factor to the values obtained for potassium. The prediction error between the calculated and actual sodium values determined using inductively coupled plasma atomic emission spectrophotometry (ICP-AES) was 0.004%, and this confirms that the NIRS procedure is a viable option for the determination of sodium and potassium content in this type of sample.

In this work, non-invasive near-infrared spectroscopy (NIRS) combined with chemometrics was evaluated as a possible online analytical technique to categorize pieces of cured ham on the industrial production line based on their maximum sodium content. Stifle muscle was selected for the development of the NIRS prediction models because it is the one with the highest sodium content and the easiest in terms of accessibility for spectral measurement. In the study, samples with varying thicknesses were taken. The suitability of this method is demonstrated when a 5 mm sample is used for the construction of the model, obtaining the best fit with an R 2 cv of 92% and a prediction error of 0.11% sodium that coincides with the error of the reference method. In conclusion, a method is proposed for the direct determination of sodium content on the production line which allows the different pieces of ham to be quickly categorized according to their salt content., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Introduction/background: Breast cancer survivors (BCS) frequently show upper limb dysfunctions. The forearm muscle activity measured by surface electromyography (sEMG) in this population has not been studied. This study aimed to describe forearm muscle activity in BCS, as well as to assess its possible relationship with other variables related to upper limb functionality and cancer-related fatigue (CRF)., Materials and Methods: A cross-sectional study was carried out including 102 BCS as volunteers at a secondary care in Malaga, Spain. BCS were included if they were aged between 32 and 70 years old, without evidence of cancer recurrence at the time of recruitment. The forearm muscle activity (microvolts, µV) was assessed by sEMG during the handgrip test. The handgrip strength was assessed by dynamometry (kg), the upper limb functionality (%) was measured by the upper limb functional index (ULFI) questionnaire and the CRF was also assessed by revised Piper Fatigue Scale (0-10 points)., Results: BCS reported reduced forearm muscle activity (287.88 µV) and reduced handgrip strength (21.31 Kg), a good upper limb functionality (68.85%), and a moderate cancer-related fatigue (4.74). Forearm muscle activity showed a poor significant correlation (r = -0.223, P = .038) with the CRF. Handgrip strength showed a poor correlation with the upper limb functionality (r = 0.387, P < .001) and age (r=-0.200, P = .047)., Conclusion: BCS showed a reduced forearm muscle activity. BCS also presented a poor correlation between forearm muscle activity and handgrip strength. Both outcomes tended to lower values with higher levels of CRF, while preserving a good upper limb functionality., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Multiple sclerosis (MS) is a chronic, inflammatory, demyelinating disease of autoimmune origin, in which inflammation and demyelination lead to neurodegeneration and progressive disability. Treatment is aimed at slowing down the course of the disease and mitigating its symptoms. One of the first-line treatments used in patients with MS is glatiramer acetate (GA). However, in clinical practice, a response rate of between 30% and 55% is observed. This variability in the effectiveness of the medication may be influenced by genetic factors such as polymorphisms in the genes involved in the pathogenesis of MS. Therefore, this review assesses the impact of genetic variants on the response to GA therapy in patients diagnosed with MS. The results suggest that a relationship exists between the effectiveness of the treatment with GA and the presence of polymorphisms in the following genes: CD86 , CLEC16A , CTSS , EOMES , MBP , FAS , TRBC1 , IL1R1 , IL12RB2 , IL22RA2 , PTPRT , PVT1 , ALOX5AP , MAGI2 , ZAK , RFPL3 , UVRAG , SLC1A4 , and HLA-DRB1*1501 . Consequently, the identification of polymorphisms in these genes can be used in the future as a predictive marker of the response to GA treatment in patients diagnosed with MS. Nevertheless, there is a lack of evidence for this and more validation studies need to be conducted to apply this information to clinical practice.

Introduction: Proper nutrition during pregnancy is important to prevent nutritional imbalances that interfere with pregnancy. Micronutrients play critical roles in embryogenesis, fetal growth, and maternal health, as energy, protein, vitamin, and mineral needs can increase during pregnancy. Increased needs can be met by increasing the intake of dietary micronutrients. Severe micronutrient deficiency or excess during pregnancy can have negative effects on fetal growth (intrauterine growth retardation, low birth weight, or congenital malformations) and pregnancy development (pre-eclampsia or gestational diabetes). We investigate whether it is necessary to continue micronutrient supplementation during pregnancy to improve women's health in this stage and whether this supplementation could prevent and control pathologies associated with pregnancy., Aim: The present review aims to summarize evidence on the effects of nutritional deficiencies on maternal and newborn morbidity., Methods: This aim is addressed by critically reviewing results from published studies on supplementation with different nutrients during pregnancy. For this, major scientific databases, scientific texts, and official webpages have been consulted. PubMed searches using the terms "pregnancy" OR "maternal-fetal health" AND "vitamins" OR "minerals" OR "supplementation" AND "requirement" OR "deficiency nutrients" were performed., Results: There are accepted interventions during pregnancy, such as folic acid supplementation to prevent congenital neural tube defects, potassium iodide supplementation to correct neurodevelopment, and oral iron supplementation during the second half of pregnancy to reduce the risk of maternal anemia and iron deficiency. A number of micronutrients have also been associated with pre-eclampsia, gestational diabetes mellitus, and nausea and vomiting in pregnancy. In general, experimental studies are necessary to demonstrate the benefits of supplementation with different micronutrients and to adjust the recommended daily doses and the recommended periconceptional nutrition for mothers., Conclusions: Presently, there is evidence of the benefits of micronutrient supplementation in perinatal results, but indiscriminate use is discouraged due to the fact that the side effects of excessive doses are not known. Evidence supports the idea that micronutrient deficiencies negatively affect maternal health and the outcome of pregnancy. No single micronutrient is responsible for the adverse effects; thus, supplementing or correcting one deficiency will not be very effective while other deficiencies exist.

First-line therapy with interferon beta (IFN-β), involved in gene expression modulation in immune response, is widely used for multiple sclerosis. However, 30-50% of patients do not respond optimally. Variants in CBLB, CTSS, GRIA3, OAS1 and TNFRSF10A genes have been proposed to contribute to the variation in the individual response. The purpose of this study was to evaluate the influence of gene polymorphisms on the IFN-β response in relapsing-remitting multiple sclerosis (RRMS) patients. CBLB (rs12487066), GRIA3 (rs12557782), CTSS (rs1136774), OAS1 (rs10774671) and TNFRSF10A (rs20576) polymorphisms were analysed by Taqman in 137 RRMS patients. Response to IFN-β and change in the Expanded Disability Status Scale (EDSS) after 24 months were evaluated using multivariable logistic regression analysis. Carriers of at least one copy of the C allele of CTSS-rs1136774 had a better response to IFN-β (p = 0.0423; OR = 2.94; CI95% = 1.03, 8.40). Carriers of TT genotype of TNFRSF10A-rs20576 had a higher probability of maintaining their EDSS stable after 24 months of IFN-β treatment (p = 0.0251; OR = 5.71; CI95% = 1.39, 31.75). No influence of CBLB (rs12487066), OAS1 (rs10774671) and GRIA3 (rs12557782) gene polymorphisms in the variation of the individual response to IFN-β was shown. Our results suggest that the TNFRSF10A-rs20576 and CTSS-rs1136774 gene polymorphisms influence the response to IFN-β after 24 months, while the CBLB (rs12487066), OAS1 (rs10774671) or GRIA3 (rs12557782) gene polymorphisms had no effect on the variation of the individual response to IFN-β., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Aims: We aimed to analyze the relationship between the initial chest X-ray findings in patients with severe acute respiratory syndrome due to infection with SARS-CoV-2 and eventual clinical worsening and to compare three systems of quantifying these findings., Material and Methods: This retrospective study reviewed the clinical and radiological evolution of 265 adult patients with COVID-19 attended at our center between March 2020 and April 2020. We recorded data related to patients' comorbidities, hospital stay, and clinical worsening (admission to the ICU, intubation, and death). We used three scoring systems taking into consideration 6 or 8 lung fields (designated 6 A, 6 B, and 8) to quantify lung involvement in each patient's initial abnormal chest X-ray and to classify its severity as mild, moderate, or severe, and we compared these three systems. We also recorded the presence of alveolar opacities and linear opacities (fundamentally linear atelectasis) in the first chest X-ray with pathologic findings., Results: In the χ2 analysis, moderate or severe involvement in the three classification systems correlated with hospital admission (p = 0.009 in 6 A, p = 0.001 in 6 B, and p = 0.001 in 8) and with death (p = 0.02 in 6 A, p = 0.01 in 6 B, and p = 0.006 in 8). In the regression analysis, the most significant associations were 6 B with alveolar involvement (OR 2.3; 95%CI 1.1.-4.7; p = 0.025;) and 8 with alveolar involvement (OR 2.07; 95% CI 1.01.-4.25; p = 0.046). No differences were observed in the ability of the three systems to predict clinical worsening by classifications of involvement in chest X-rays as moderate or severe., Conclusion: Moderate/severe extension in the three chest X-ray scoring systems evaluating the extent of involvement over 6 or 8 lung fields and the finding of alveolar opacities in the first abnormal X-ray correlated with mortality and the rate of hospitalization in the patients studied. No significant difference was found in the predictive ability of the three classification systems proposed., (© 2021 SERAM. Published by Elsevier España, S.L.U. All rights reserved.)

The aim of the present study was to investigate the preventive potential of pentoxifylline, atorvastatin and trans-caryophyllene in oral mucositis through histopathological analysis of wounds in the oral mucosa of Wistar rats treated with 5-FU, and to evaluate the immunomodulatory effect of these drugs on serum nitrite production, in situ IFN-γ, TNF-α and TGF-β, and TNF-α in tissues. A total of 32 male Wistar rats with an average age of 9 weeks and an average body weight of 250 g were divided into four treatment groups: Saline, trans-caryophyllene, pentoxifylline and atorvastatin. Oral mucositis was then induced. On days 3 and 4, the mucosa of the mouth of eight pre-treated animals in each group was bilaterally scarified twice with the tip of a sterile needle, with an anesthetic solution. Mucosal samples from animals treated with trans-caryophyllene preserved a thin epithelial lining associated with focal perivascular inflammatory infiltrates. Pentoxifylline-treated animals exhibited total epithelial loss in oral wounds with severe inflammatory infiltrates and mild re-epithelialization associated with mild and diffuse inflammatory infiltrates. Samples from atorvastatin-treated animals exhibited no epithelial dissolution, with preserved thin lining and mild diffuse inflammatory infiltrates. The analysis of TNF-α expression revealed improved results in trans-caryophyllene animals. The analysis of TGF-β expression revealed positive mononuclear cells. Preventive treatment with atorvastatin was demonstrated to modulate the serum expression levels of TNF-α during all stages of the experiment. Treatment with trans-caryophyllene modulated serum IFN-γ levels negatively, whereas treatment with atorvastatin and trans-caryophyllene maintained lower levels of IFN-γ compared with the control group., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Da Cruz Campos et al.)

The introduction of new therapies for the treatment of multiple sclerosis (MS) is a very recent phenomenon and little is known of their mechanism of action. Moreover, the response is subject to interindividual variability and may be affected by genetic factors, such as polymorphisms in the genes implicated in the pathologic environment, pharmacodynamics, and metabolism of the disease or in the mechanism of action of the medications, influencing the effectiveness of these therapies. This review evaluates the impact of pharmacogenetics on the response to treatment with new therapies in patients diagnosed with MS. The results suggest that polymorphisms detected in the GSTP1 , ITGA4 , NQO1 , AKT1 , and GP6 genes, for treatment with natalizumab, ZMIZ1 , for fingolimod and dimethyl fumarate, ADA , for cladribine, and NOX3 , for dimethyl fumarate, may be used in the future as predictive markers of treatment response to new therapies in MS patients. However, there are few existing studies and their samples are small, making it difficult to generalize the role of these genes in treatment with new therapies. Studies with larger sample sizes and longer follow-up are therefore needed to confirm the results of these studies.

Objectives: Multiple sclerosis (MS) is a neurodegenerative chronic inflammatory. Mutations in the vitamin D receptor (VDR) gene can substantially affect serum vitamin D levels or alter its functionality, and can consequently increase susceptibility to developing MS. The objective of this study was to evaluate the association between polymorphisms in the VDR gene and risk of MS in a (Spanish) Caucasian population., Patients and Methods: We conducted a retrospective case-control study comprising 209 patients with relapsing-remitting multiple sclerosis (RRMS) and 836 controls of Caucasian origin from southern Spain. The ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms were determined by allelic discrimination real-time PCR using TaqMan probes., Results: The recessive logical regression model, adjusted for age and sex, revealed that the TT genotype for VDR FokI (rs2228570) polymorphism was associated with higher risk of MS (P = 0.0150; OR = 1.82; 95% CI = 1.12-2.94; TT vs. CT + CC). No association between the other polymorphisms and development of MS was found in any of the models analyzed. The haplotype analysis, adjusted for age, smoking, and sex, did not find any statistically significant association between the haplotypes analyzed and risk of MS., Conclusions: The VDR FokI (rs2228570) polymorphism was significantly associated with developing MS. We found no influence of the ApaI (rs7975232), BsmI (rs1544410), Cdx2 (rs11568820), FokI (rs2228570), and TaqI (rs731236) gene polymorphisms on the risk of developing MS in our patients., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

ABCB1, DPYD, MHTFR, XRCC1, ERCC1, GSTP1 and UGT1A1 genetic variants affect proteins related to CRC chemotherapy toxicity. A retrospective cohort study was conducted in 194 CRC patients. In first line treatment, DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 4.85; p = 0.03); GSTP1 G-allele (OR = 3.01; p = 0.005) and MTHFR rs1801133 T allele (OR = 2.51; p = 0.03) with respiratory toxicity; GSTP1 G-allele with cardiovascular toxicity (OR = 4.05; p = 0.01); ERCC1 rs11615 GG genotype with neurological toxicity (OR = 3.98; p = 0.01) and with asthenia (OR = 2.91; p = 0.08); XRCC1 rs1799782 T allele (OR = 0.31; p = 0.03) and GSTP1 G-allele (OR = 1.81; p = 0.01) with cutaneous toxicity. In second line treatment, XRCC1 rs1799782 T-allele was associated with asthenia (OR = 0.17; p = 0.03) and XRCC1 rs25487 T-allele with gastrointestinal toxicity (OR = 3.03; p = 0.005). After stratifying by treatment, in the 5-Fluorouracil group, the DPYD rs17376848 AG genotype was associated with hematological toxicity (OR = 2.76; p = 0.003), ABCB1 rs1045642 T-allele with the need of treatment adjustment due to toxicity (OR = 3.06; p = 0.01), and rs1045642 CC genotype with gastrointestinal toxicity (OR = 5.80; p = 0.03). In the capecitabine group, the MTHFR rs1801131 CC genotype was associated with asthenia (OR = 3.48; p = 0.009). In the oxaliplatin group, rs1045642 TT genotype was associated with the need to adjust treatment (OR = 0.32; p = 0.02), ERCC1 rs11615 GG genotype with asthenia (OR = 3.01; p = 0.01) and rs1615 GSTP1 GG genotype with respiratory toxicity (OR = 5.07; p = 0.009). ABCB1 rs1045642 T-allele reduces the need for treatment modification with both 5FU and oxaliplatin. Although several biomarkers predicted different toxic effects, they cannot be considered as risk factors for severe toxicity., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Treatment with interferon beta (IFNβ) is one of the first-line treatments for multiple sclerosis. In clinical practice, however, many patients present suboptimal response to IFNβ, with the proportion of non-responders ranging from 20 to 50%. This variable response can be affected by genetic factors, such as polymorphisms in the genes involved in the disease state, pharmacodynamics, metabolism or in the action mechanism of IFNβ, which can affect the efficacy of this drug. This review assesses the impact of pharmacogenetics studies on response to IFNβ treatment among patients diagnosed with relapsing-remitting multiple sclerosis (RRMS). The results suggest that the detection of polymorphisms in several genes (CD46, CD58, FHIT, IRF5, GAPVD1, GPC5, GRBRB3, MxA, PELI3 and ZNF697) could be used in the future as predictive markers of response to IFNβ treatment in patients diagnosed with RRMS. However, few studies have been carried out and they have been performed on small sample sizes, which makes it difficult to generalize the role of these genes in IFNβ treatment. Studies on large sample sizes with longer term follow-up are therefore required to confirm these results., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

NIR spectroscopy combined with chemometric methods has been used to develop a prediction models of the most influential parameters in curing process of two types of hams (140 hams) using different salting techniques, lean hams salted on a tray and fatty hams in a tub, in which sodium is partially replaced. Spectral data were examined by principal component analysis and cross-validated calibration equations were developed using partial-least squares regression. Calibration errors for each parameter, obtained from cross validation (RMSECV), were similar to those obtained by reference method. For lean and fatty hams the RMSECV values were: Moisture 0.78% and 0.80; Fat 2.5 and 1.2%; Protein 0.7 and 1.7%; water activity 0.008 and 0.006; Proteolysis Index 1.6 and 1.7%; Sodium 0.11 and 0.10%; and Potassium 0.04 and 0.10. Results allow the prediction of the parameters involved in ham curing process, demonstrating the viability of the proposed method for the control and monitoring of the different stages until obtaining the final product., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Temperature fluctuations are a key factor in the development of prediction models using near infrared spectroscopy (NIRS). In the present study, this influence has been investigated and a methodology has been proposed to reduce the effect of sample temperature on NIRS model prediction of the sodium content in dry-cured ham slices. Spectra were taken directly from the slices using a remote measurement probe (for non-contact analysis) at three different temperature ranges: -12 °C to -5°C, -5°C to 10 °C and 10 °C to 20 °C. Local and global temperature compensation methods were established. Partial-least squares (PLS) regression was used as a chemometrics tool to perform the calibrations. The results showed that local models were sensitive to changes in temperature, while a global temperature model using sample spectra over the entire temperature range showed good prediction ability, reducing the error caused by temperature fluctuations to acceptable levels for practical applications., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

In the present study, non-invasive near infrared spectroscopy (NIRS) was evaluated as a potential on-line analytical technique to predict the sodium content in dry-cured ham slices. Samples of 310 packages were scanned by applying a remote fibre-optic probe to the surface of the slices, at different temperatures, with no previous manipulation. The sodium content of the meat samples was determined by a reference method based on Inductively Coupled Plasma Atomic Emission Spectrophotometry (ICP-AES) after chemical digestion. Partial least squares (PLS) regression was used as a chemometrics method to perform the calibrations. The models yielded acceptable results with cross validation correlation coefficients (R 2 CV ) determined 86.2-90.2%. The prediction capacity reached in the external validation was 3.63, with a standard prediction error of 0.12% Na. These results show that NIR measurements could be implemented on the packaging line of dry-cured ham slices to provide accurate and relevant information about the sodium content of each packaged products., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Introduction:: Transforming growth factor beta 1 (TGFB1) and platelet-derived growth factor (PDGF) are the main cytokines related to hepatic fibrogenesis., Methods:: RNA isolated from the platelets and hepatic tissue of 43 HCV carriers was used for quantitative polymerase chain reaction to determine TGFB1, PDGFA, and PDGFB RNA expression., Results:: The mRNA expression of PDGFA in platelets was significantly lower in the group with advanced fibrosis than in the group with early-stage fibrosis. TGFB1 was more frequently expressed in platelets than in hepatic tissue, which was different from PDGFB., Conclusions:: A pathway mediated by overexpression of TGFB1 via PDGFA in megakaryocytes could be involved in the development of fibrosis.

Colorectal cancer is the fourth most prevalent cancer in the United States, yet there are no reliable noninvasive early screening methods available. Serum-based glycomic profiling has the necessary sensitivity and specificity to distinguish disease states and provide diagnostic potential for this deadly form of cancer. We applied microchip electrophoresis and MALDI-TOF-MS-based glycomic procedures to 20 control serum samples and 42 samples provided by patients diagnosed with colorectal cancer. Within the identified glycans, the position of fucose units was located to quantitate possible changes of fucosyl isomeric species associated with the pathological condition. MALDI-MS data revealed several fucosylated tri- and tetra-antennary glycans which were significantly elevated in their abundance levels in the cancer samples and distinguished the control samples from the colorectal cancer cohort in the comprehensive profiles. When compared to other cancers studied previously, some unique changes appear to be associated with colorectal cancer, being primarily associated with fucosyl isomers. Through MS and microchip electrophoresis-based glycomic methods, several potential biomarkers were identified to aid in the diagnosis and differentiation of colorectal cancer. With its unique capability to resolve isomers, microchip electrophoresis can yield complementary analytical information to MS-based profiling.

To characterize the structures of N-glycans derived from human serum, we report a strategy that combines microchip electrophoresis, standard addition, enzymatic digestion, and matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS). We compared (i) electrophoretic mobilities of known N-glycans from well-characterized (standard) glycoproteins through standard addition, (ii) the electrophoretic mobilities of N-glycans with their molecular weights determined by MALDI-MS, and (iii) electrophoretic profiles of N-glycans enzymatically treated with fucosidase. The key step to identify the sialylated N-glycans was to quantitatively neutralize the negative charge on both α2,3- and α2,6-linked sialic acids by covalent derivatization with methylamine. Both neutralized and nonsialylated N-glycans from these samples were then reacted with 8-aminopyrene-1,3,6-trisulfonic acid (APTS) to provide a fluorescent label and a triple-negative charge, separated by microchip electrophoresis, and detected by laser-induced fluorescence. The methylamidation step leads to a 24% increase in the peak capacity of the separation and direct correlation of electrophoretic and MALDI-MS results. In total, 37 unique N-glycan structures were assigned to 52 different peaks recorded in the electropherograms of the serum samples. This strategy ensures the needed separation efficiency and detectability, easily resolves linkage and positional glycan isomers, and is highly reproducible.

Introduction: In this study, we evaluated hepatitis C virus (HCV) and human immunodeficiency virus (HIV) - platelet interactions in vitro as well as human platelets antigen (HPA) polymorphisms., Methods: Platelets were obtained from 100 healthy HPA-genotyped volunteer donors and incubated with HIV or HCV. The viral load after in vitro exposure was detected., Results: The viral load in the platelets after exposure to the virus was higher in the HIV exposure than in the HCV exposure., Conclusions: HIV-platelet ligation could be more efficient than HCV-platelet interaction. Further, the HPA-1b allele seems to influence the interaction of platelets with HCV.

To evaluate the associations of HPA polymorphisms -1, -3, and -5 with HIV/HCV coinfection were included in this study 60 HIV/HCV-coinfected patients from the Sao Paulo State health service centers. Data reported by Verdichio-Moraes et al. (2009: J. Med Virol 81:757-759) were used as the non-infected and HCV monoinfected groups. Human Platelet Polymorphism genotyping was performed in 60 Patients co-infected with HIV/HCV by PCR-SSP or PCR-RFLP. HIV subtyping and HCV genotyping was performed by RT-PCR followed sequencing. The data analyses were performed using the χ2 test or Fisher's Exact Test and the logistic regression model. Patients coinfected with HIV/HCV presented HCV either genotype 1 (78.3%) or non-1 (21.7%) and HIV either subtype B (85.0%) or non-B (15%). The Human Platelet Polymorphism-1a/1b genotype was more frequent (P < 0.05) in HIV/HCV coinfection than in HCV monoinfection and the allelic frequency of Human Platelet Polymorphism-5b in the Patients coinfected with HIV/HCV was higher (P < 0.05) than in HCV monoinfected cases and non-infected individuals. These data suggest that the presence of specific HPA allele on platelets could favor the existence of coinfection. On the other hand, Human Platelet Polymorphism-5a/5b was more frequent (P < 0.05) in HIV/HCV coinfected and HCV monoinfected groups than in the non-infected individuals, suggesting that this platelet genotype is related to HCV infection, regardless of HIV presence. Results suggest that the Human Platelet Polymorphism profile in HIV/HCV coinfected individuals differs from the one of both HCV monoinfected and non-infected population. So, the Human Platelet Polymorphism can be a genetic marker associated with HIV/HCV coinfection., (© 2015 Wiley Periodicals, Inc.)

Introduction: Hepatic fibrosis progression in patients with chronic hepatitis C virus infections has been associated with viral and host factors, including genetic polymorphisms. Human platelet antigen polymorphisms are associated with the rapid development of fibrosis in HCV-monoinfected patients. This study aimed to determine whether such an association exists in human immunodeficiency virus-1/hepatitis C virus-coinfected patients., Methods: Genomic deoxyribonucleic acid from 36 human immunodeficiency virus-1/hepatitis C virus-coinfected patients was genotyped to determine the presence of human platelet antigens-1, -3, or -5 polymorphisms. Fibrosis progression was evaluated using the Metavir scoring system, and the patients were assigned to two groups, namely, G1 that comprised patients with F1, portal fibrosis without septa, or F2, few septa (n = 23) and G2 that comprised patients with F3, numerous septa, or F4, cirrhosis (n = 13). Fisher's exact test was utilized to determine possible associations between the human platelet antigen polymorphisms and fibrosis progression., Results: There were no deviations from the Hardy-Weinberg equilibrium in the human platelet antigen systems evaluated. Statistically significant differences were not observed between G1 and G2 with respect to the distributions of the allelic and genotypic frequencies of the human platelet antigen systems., Conclusion: The greater stimulation of hepatic stellate cells by the human immunodeficiency virus and, consequently, the increased expression of transforming growth factor beta can offset the effect of human platelet antigen polymorphism on the progression of fibrosis in patients coinfected with the human immunodeficiency virus-1 and the hepatitis C virus.

Introduction: The nutritional status (NS) of patients on hemodialysis (HD) is a major concern and challenge. Malnutrition is common in these patients and is related to poorer clinical outcomes., Objectives: To assess the association between the NS and the interdialytic weight gain (IDWG) of patients with chronic kidney disease (CKD) on HD., Methods: Cross-sectional study with 322 patients older than 18 years. The NS was assessed by body mass index (BMI), percentage body fat estimated by the sum of four skinfolds (triceps, biceps, subscapular and supra iliac), lean body mass (LBM), serum creatinine and albumin and rate of nitrogen appearance (PNA). The IDWG was evaluated from the sum of the weight difference of 12 hemodialysis sessions (IDWGm)., Results: Considering the sample into quartiles IDWGm, it was found that BMI, LBM, serum creatinine ( p < 0.001) and PNA ( p = 0.011) were directly correlated. There was no association between IDWGm and serum albumin. Using multivariate analysis, it was found that the prevalence of patients with BMI suitability and serum creatinine were significantly higher for patients in the bottom quartile with respect to the first IDWGm., Conclusion: The NS is positively associated with IDWG. The results point to the need for individualized assessment of IDWG and cautious in order not to generalize a recommendation that does not meet the expectations of maintaining and promoting the nutritional status of these patients.

Introduction: Underreporting of energy intake is not much studied in hemodialysis population., Objective: To evaluate the underreporting of energy intake and associated factors in hemodialysis patients., Methods: A cross-sectional study, with 344 patients stable adults, of ten hemodialysis centers in Goiânia-GO. Energy intake was assessed by six 24-hour dietary recalls and basal metabolic rate (BMR) was estimated using the Harris Benedict equation. It was considered as underreporting when the ratio between the average energy intake and basal metabolic rate was lower than1.27. For analysis of factors associated with underreporting, the Poisson regression with robust variance estimation was applied., Results: The prevalence of underreporting was 65.7%, being more significant in individuals who are overweight and in the non dialysis days. The result of the multivariate analysis identified four factors independently associated with the underreporting: being a female (PR = 1.27, CI = 1.10 to 1.46), body mass index ≥ 25 kg/m2 (PR = 1.29, CI = 1.12 to 1.48), three meals or lower/day (PR = 1.31, CI = 1.14 to 1.51) and hemodialysis length lower than 5 years (PR = 1.19CI = 1.01 to 1.40)., Conclusion: The population showed a high prevalence of underreporting of energy intake. Being a female, presenting overweight, lower number of meals/day and lower length time on hemodialysis were factors associated with underreporting.

Malignant neoplasia represents the second cause of disease-related mortality and, among all patients diagnosed with cancer, 70% will receive chemotherapy during the course of treatment. As a consequence, an increasing number of researchers have focused their attention on the search for more specific anticancer therapies associated with fewer side effects. Leukopenia is an important adverse effect associated with chemotherapy. Secondary infection is very common among leukopenic patients, directly affecting the continuity of the chemotherapeutic treatment and leading to possible complications in tumor immune defense. Atorvastatin, a type of statin, is a known agent used to control hypercholesterolemia. Trans-caryophyllene, isolated from a resinous oil extracted from the copaiba tree, possesses anti-inflammatory and analgesic properties. The AIM of the present study was to evaluate, through a complete leukocyte count, the systemic immunomodulation potential of pentoxifylline (PTX), atorvastatin and trans-caryophyllene, as well as the possible prophylactic role of these drugs against secondary leukopenia, in an experimental chemotherapy model induced by 5-fluorouracil (5-FU) in wistar rats. A total of 32 male wistar rats were used, 24 of which were submitted to treatment with atorvastatin, PTX and trans-caryophyllene prior to the administration of chemotherapy. The Shapiro-Wilk test was used to verify normality and the Kruskal-Wallis test was used for negative data in the normality test. Among the drugs selected, atorvastatin exhibited the best preventive potential in regards to leukopenia secondary to experimental chemotherapy induced by 5-FU, in comparison to the group receiving saline solution, while PTX amplified such alterations in the leukograms of the animals in this trial.

Although HCV has hepatic tropism, the presence of the virus in extra-hepatic compartments has been well documented. Platelets have been described as carriers of the virus in the circulation and may be a natural reservoir for the virus. However, few studies have been performed to evaluate the levels of HCV RNA in plasma and platelets are equal or differ in some way. Therefore, the aim of this study was to perform a comparative evaluation of the stability of HCV RNA in plasma and isolated platelets. Four aliquots of whole plasma obtained from patients infected with HCV were incubated at 37 °C for 0, 48, 96 and 144 h. After incubation, the plasma and platelet pellet was obtained from each aliquot. Viral RNA in plasma and platelets was quantified by q-PCR. The results showed a decrease in HCV RNA levels in plasma with incubation time. However, platelet HCV RNA levels were stable up to 144 h incubation. The results of this study showed that HCV RNA in platelets, although at lower concentrations than in plasma, is preserved from degradation over time, suggesting that the virus may persist longer in the body when associated with platelets, which could have an impact on the efficiency of antiviral therapy.

While assessing immunization programmes, not only vaccination coverage is important, but also timely receipt of vaccines. We estimated both vaccination coverage and timeliness, as well as reasons for non-vaccination, and identified predictors of delayed or missed vaccination, for vaccines of the first two years of age, in El Salvador. We conducted a cluster survey among children aged 23-59 months. Caregivers were interviewed about the child immunization status and their attitudes towards immunization. Vaccination dates were obtained from children immunization cards at home or at health facilities. We referred to the 2006 vaccination schedule for children below two years: one dose of BCG (Bacillus Calmette-Guérin) at birth; rotavirus at two and four months; three doses of pentavalent - DTP (diphtheria-tetanus-pertussis), hepatitis B, and Haemophilus influenzae type b (Hib) - and of oral poliomyelitis vaccine (polio) at two, four, and six months; first MMR (measles-mumps-rubella) at 12 months; and first boosters of DTP and OPV at 18 months. Timeliness was assessed with Kaplan-Meier analysis; Cox and logistic regression were used to identify predictors of vaccination. We surveyed 2550 children. Coverage was highest for BCG (991%; 95% CI: 98.8-99.5) and lowest for rotavirus, especially second dose (86.3%; 95% CI: 84.2-88.4). The first doses of MMR and DTP had 991% (95% CI: 98.5-99.6) and 977% (95% CI: 970-985), respectively. Overall coverage was 837% (95% CI: 81.4-86.0); 96.4% (95% CI: 95.4-97.5), excluding rotavirus. However, only 26.7% (95% CI: 24.7-28.8) were vaccinated within the age interval recommended by the Expanded Programme on Immunization. Being employed and using the bus for transport to the health facility were associated with age-inappropriate vaccinations; while living in households with only two residents and in the "Paracentral", "Occidental", and "Oriental" regions was associated with age-appropriate vaccinations. Vaccination coverage was high in El Salvador, but general timeliness and rotavirus uptake could be improved., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

Introduction: The presence of excess weight, especially visceral obesity contributes to the increased risk of metabolic and cardiovascular complications in patients with chronic kidney disease., Objective: To determine the prevalence and associated factors with abdominal obesity in patients on hemodialysis (HD)., Methods: Cross-sectional study with 344 patients older than 18 years. Abdominal obesity was defined as waist circumference > 94 cm in men and > 80 cm in women. The independent variables involved socioeconomic, demographic, lifestyle, duration of HD, food consumption and body mass index (BMI). The analysis of associated factors was performed by multiple Poisson regression, remaining in the final model variables with p < 0.05., Results: The prevalence of abdominal obesity was 44.77% and was more prevalent in women (55.71%) than in men (37.25%), p = 0.001. The end result of the multivariate analysis identified factors associated with abdominal obesity in men and women: age over 40 years, protein intake below 1.2 g/kg/day and BMI > 25 kg/m². In men the economic class D/E remained associated with abdominal obesity, p < 0.05., Conclusion: There was a high prevalence of abdominal obesity in hemodialysis patients. Age greater than 40 years, lower socioeconomic classes, below the recommended protein intake and overweight were associated with abdominal obesity.

The aim of this communication was to describe the detection of the coexistence of HIV-1 variant with dipeptide insertion between codons 69 and 70 of reverse transcriptase. These variants were isolated from a 16-year-old male patient, undergoing treatment in the city of Marilia, SP, Southeastern Brazil. After confirmation of treatment failure, resistance to antiretroviral drugs testing was performed and two variants with the insertions of the aminoacids Ser-Gly/Ser-Ala at codon 69 of reverse transcriptase were detected, besides the T69S mutation. These insertions have low prevalence, have not been reported in situations of coexistence in Brazil and are related to multidrug resistance, which makes this epidemiological finding relevant.

Introduction: Despite hepatocytes being the target cells of hepatitis C virus (HCV), viral ribonucleic acid RNA has been detected in other cells, including platelets, which have been described as carriers of the virus in the circulation of infected patients. Platelets do not express cluster differentiation 81 CD81, the main receptor for the virus in hepatocytes, although this receptor protein has been found in megakaryocytes. Still, it is not clear if HCV interacts with platelets directly or if this interaction is a consequence of its association with megakaryocytes. The aim of this study was to evaluate the interaction of HCV with platelets from non-infected individuals, after in vitro exposure to the virus., Methods: Platelets obtained from 50 blood donors not infected by HCV were incubated in vitro at 37°C for 48h with serum containing 100,000IU∕mL of genotype 1 HCV. After incubation, RNA extracted from the platelets was assayed for the presence of HCV by reverse transcription – polymerase chain reaction RT-PCR., Results: After incubation in the presence of virus, all samples of platelets showed HCV RNA., Conclusions: The results demonstrate that, in vitro, the virus interacts with platelets despite the absence of the receptor CD81, suggesting that other molecules could be involved in this association.

The goal of treatment of chronic hepatitis C is to achieve a sustained virological response, which is defined as exhibiting undetectable hepatitis C virus (HCV) RNA levels in serum following therapy for at least six months. However, the current treatment is only effective in 50% of patients infected with HCV genotype 1, the most prevalent genotype in Brazil. Inhibitors of the serine protease non-structural protein 3 (NS3) have therefore been developed to improve the responses of HCV-infected patients. However, the emergence of drug-resistant variants has been the major obstacle to therapeutic success. The goal of this study was to evaluate the presence of resistance mutations and genetic polymorphisms in the NS3 genomic region of HCV from 37 patients infected with HCV genotype 1 had not been treated with protease inhibitors. Plasma viral RNA was used to amplify and sequence the HCV NS3 gene. The results indicate that the catalytic triad is conserved. A large number of substitutions were observed in codons 153, 40 and 91; the resistant variants T54A, T54S, V55A, R155K and A156T were also detected. This study shows that resistance mutations and genetic polymorphisms are present in the NS3 region of HCV in patients who have not been treated with protease inhibitors, data that are important in determining the efficiency of this new class of drugs in Brazil.

CDKN2A promoter hypermethylation has been widely related to many cancers. In astrocytomas, although CDKN2A (p16(INK4A) protein) is often inactivated, there are still some controversial issues regarding the mechanism by which this alteration occurs. Thus, we analyzed a series of astrocytomas to assess the association between CDKN2A expression and methylation of grade I-IV tumors (WHO) and clinicopathological parameters. DNA extracted from formalin-fixed paraffin-embedded material of 93 astrocytic tumors was available for CDKN2A promoter methylation analysis and p16(INK4A) expression by methylation-specific PCR and immunohistochemistry, respectively. A strong negative correlation between nuclear and cytoplasmic immunostaining and CDKN2A promoter methylation was found. Additionally, a significant negative correlation between CDKN2A promoter methylation and age was observed; also, female patients had statistically more CDKN2A methylated promoters (p = 0.036) than men. In conclusion, CDKN2A inactivation by promoter methylation is a frequent event in astrocytomas and it is related to the age and sex of patients., (Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.)

Summary: In sickle cell disease, erythroid hyperplasia causes trabecular destruction leading to low bone density. This condition could be suspected by the radiomorphometric indices and your diagnosis becomes relevant in a multidisciplinary context of health care for sickle cell subjects, providing prognostics and contributing to determine adequate therapeutic and preventive actions., Introduction: The aim of this study was to assess the risk of low bone density in subjects with sickle cell disease (SCD) through analysis of panoramic radiographic exams by radiomorphometric indices., Methods: Seventy-eight Brazilian subjects with SCD took part in this study and were subdivided into four groups: (I) 31 SCD subjects aged under 40 years; (II) 13 SCD subjects aged 40 years or more; (III) 12 normal subjects aged under 40 years; and (IV) 22 normal subjects aged 40 years or more. In the panoramic radiographs, the mandibular cortical index (MCI) classification, increased spacing of the trabecular bone, panoramic mandibular index (PMI), and mental index (MI) were evaluated. Exact Fisher's test was used to compare age between the different groups. Descriptive analysis of the data was performed to evaluate the simple visual estimation of low bone density (increased bone trabecular space and MCI), and a one-way analysis of variance (Bonferroni criteria) was used to compare the means of the quantitative indices (PMI and MI). The significance level was p < 0.05., Results: In the MCI classification, C2 was more prevalent, especially in groups I and IV. Increased spacing of the trabecular bone was more frequent in groups I and II. MI did not show a statistically significant difference among the groups. PMI showed a statistically significant difference only between groups III and IV., Conclusions: The radiomorphometric indices applied in the present study can be used on panoramic radiographs to detect the presence of low bone density in SCD subjects.

This study was conducted to investigate the relationship among radiographic features observed on panoramic radiographs of sickle cell disease patients and analyze their relationship with history of systemic severity of the disease. Panoramic radiographs of 71 subjects with sickle cell disease were evaluated for the presence of the following radiographic bony alterations: radiopaque areas, increased spacing of bony trabeculae, horizontal arrangement of bony trabeculae and corticalization of mandibular canal. History of clinical systemic severity was assessed through direct questioning about the frequency of vaso-occlusive crisis, history of stroke, clinical jaundice, femur head necrosis, and leg ulceration. Chi-square or Fisher's exact test were applied in order to analyze possible associations between radiographic features and history of complications, with p < 0.05 significance level. Increased spacing of bony trabeculae was statistically associated with absence of corticalization of mandibular canal (p < 0.01) and horizontal arrangement of bony trabeculae (p = 0.04). Statistically significant associations were demonstrated between history of clinical jaundice and presence of increased spacing of bony trabeculae (p = 0.02) and between history of stroke and presence of horizontal arrangement of bony trabeculae (p = 0.04). Based on the results of the current study, maxillofacial radiographic features may be associated with clinical parameters of systemic complications in sickle cell disease patients. The relationship between radiographic features and history of complications associated with clinical severity of sickle cell disease has not been demonstrated in the literature. Acknowledgment of such possible association may help establish prognosis and influence clinical treatment of systemic and oral complications.

This study investigated the prevalence of dental caries and periodontal condition in a population with sickle cell disease (SCD), analyzing some associations with disease severity. The Decayed, Missing and Filled Teeth index (DMFT) and Community Periodontal Index (CPI) were recorded for 99 individuals with SCD and 91 matched controls. Socio-demographic status, oral health behaviors, and history of clinical severity of SCD were assessed. Statistical comparisons were performed between the group with SCD and the control group, as well as multivariate logistic regression analyses with DMFT index and CPI as the dependent variables. The mean number of decayed teeth was significantly higher in individuals with HbSS. Older age, female gender, and daily smoking were identified as risk factors for higher DMFT, while older age and absence of daily use of dental floss were risk factors for the development of periodontal disease. In conclusion, risk factors known to cause caries and periodontal disease had more influence on oral health than the direct impact of SCD., (© 2012 Special Care Dentistry Association and Wiley Periodicals, Inc.)

Although progression of fibrosis in the chronic hepatitis C depends on environmental, viral, and host factors, genetic polymorphisms have been associated recently with this progression, including the expression of integrins, adhesion proteins. Some integrins expressed on the platelet membrane show polymorphic antigenic determinants called human platelet antigens (HPA), where the major ones are HPA-1, -3, -5. The association between HCV infection and HPA-5b has been demonstrated. Similarly, the HPA profile could determine if HPA is related to progression of fibrosis. The goal of this study was to evaluate the association between the frequencies of HPA-1, -3, and -5 and degree of fibrosis in HCV-infected patients. Genomic DNA from 143 HCV-infected patients was used as the source for HPA genotyping by PCR-SSP or PCR-RFLP. Progression of fibrosis was evaluated using the METAVIR scoring system, and the patients were grouped according to degree of fibrosis into G1 (n = 81, with F1, portal fibrosis without septa or F2, few septa) and G2 (n = 62, with F3, numerous septa, or F4, cirrhosis). Statistical analysis was performed using the proportional odds model. The genotypic frequency of HPA-1a/1b was significantly higher in the patients in G2. To evaluate the influence of the time of infection to the development of fibrosis and its effect on the genetic factor HPA-1, 96 patients from 143 studied were evaluated considering the time of HCV infection, and these results suggest that the HPA-1a/1b genotype promotes the development of fibrosis in HCV infection with time., (Copyright © 2011 Wiley Periodicals, Inc.)

Epstein-Barr virus (EBV) has been associated with 10% of gastric carcinomas. The aim of this study was to determine the frequency of EBV in gastric carcinomas in Brazil assessed by in situ hybridization (ISH) and PCR, which would contribute to the characterization of the clinical and pathological aspects of EBV-associated gastric carcinomas. One hundred and ninety-two gastric carcinoma cases were collected at hospitals in two Brazilian states. Seventy-three out of 151 cases were PCR(+), while 11/160 cases were ISH(+). Nine out of eleven ISH(+) cases displayed a diffuse staining pattern and 2 out of 11 a focal pattern. Both techniques showed that the EBV(+) cases were characterized by their association with males, older patients, lower gastric region, intestinal type, advanced stage and poorly to moderately differentiated tumors. The concordance between the two techniques was 55.8% (Cohen's kappa index = 0.034). Four cases were ISH(+)/PCR(-), while 49 cases were PCR(+)/ISH(-). Only two cases showed stained lymphocytes by ISH and one of them was PCR(-). The observed discrepancy between the two techniques could not be explained just by the elevated accuracy of PCR. ISH(+)/PCR(-) carcinomas may be encountered if EBV is not present in the whole tumor tissue or if there are polymorphisms in the sequences of the viral genome amplified. On the other hand, the high frequency of PCR(+) results associated with the absence of ISH staining in lymphocytes and/or tumors cells suggests that the virus may be present in tumor cells or other cell types without expressing EBER1, the target of the ISH technique.

Natural killer (NK) cells play pivotal roles in immune responses against infection with viruses, such as hepatitis C virus (HCV), and killer cell immunoglobulin-like receptors (KIRs) are related to the activation and inhibition of NK cells. The aim of this study was to investigate the possibility that KIR genes and their human leukocyte antigen (HLA) ligands influence progression to cirrhosis in patients infected with genotype 1 of HCV. A total of 145 Brazilian patients with confirmed chronic hepatitis C grouped from F0 to F4 according to fibrosis progression to cirrhosis were evaluated. Genotyping of KIR and HLA genes was performed by polymerase chain reaction with sequence-specific oligonucleotide probes. The HLA-C2 KIR ligand was more frequent in patients than in healthy controls (74.5% vs 64.3%, p = 0.04, odds ratio (OR) = 1.6, 95% confidence interval (CI) = 1.03-2.52). Moreover, the HLA-C1C2 genotype was more frequent in patients with advanced fibrosis or cirrhosis (F3-F4 group) than in patients in the F0-F2 group (61.6% vs 44.7%, p = 0.06) and in the F4 group compared with the F0-F3 group (65.7% vs 46.7%, p = 0.05, OR = 2.19, 95% CI = 1.01-4.73). NK and KIR ligands may contribute to the development of liver damage in patients chronically infected by HCV., (Copyright © 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.)

This study used panoramic radiographs to evaluate the presence of radiographic changes in the jaws of a population who had sickle cell disease (SCD). The authors compared the frequency of findings between subjects with and without SCD. Panoramic radiographs of 71 subjects with SCD (36 with HbSS and 35 with HbSC) and 52 healthy controls (HbAA) were evaluated for the presence of the following radiographic alterations: radiopaque areas, increased spacing of bony trabeculae, horizontal arrangement of bony trabeculae, and absence of mandibular canal corticalization. The control group had a significantly smaller number of all the radiographic features evaluated. Differences were not statistically significant between the groups with HbSS and HbSC, except for more trabecular spacing in the molar region in the HbSS genotype, suggesting a possible correlation between radiographic findings and disease presentation., (© 2011 Special Care Dentistry Association and Wiley Periodicals, Inc.)

Amino acid insertions in the protease have rarely been described in HIV-infected patients. One of these insertions has recently been described in codon 35, although its impact on resistance remains unknown. This study presents a case of an HIV variant with an insertion in codon 35 of the protease, described for the first time in Bauru, State of Sao Paulo, Brazil, circulating in a 38-year-old caucasian male with asymptomatic HIV infection since 1997. The variant isolated showed a codon 35 insertion of two amino acids in the protease: a threonine and an aspartic acid, resulting in the amino acid sequence E35E&#95;TD.

Temporomandibular joint (TMJ) degeneration is a frequent cause of orofacial pain. Matrix metalloproteinases (MMPs) degrade extracellular matrix components and play an important role in TMJ degeneration. We investigated the frequency of the MMP1 1G/2G polymorphism (rs1799750), the MMP3 5A/6A polymorphism (rs3025058), and the MMP9 C/T polymorphism (rs3918242) in individuals with TMJ degeneration, in order to analyze the association of polymorphisms in these genes with TMJ degeneration. The population studied comprised 117 healthy controls and 115 individuals diagnosed with TMJ degeneration upon examination of magnetic resonance imaging (MRI) and computed tomography (CT) images. Genotypes were determined using PCR restriction fragment length polymorphism (RFLP). Logistic regression analyses revealed an association between the MMP1 2G/2G genotype and degeneration; in contrast, there was no association between either the MMP3 or the MMP9 genotype and degeneration. Our results may indicate a role for the MMP1 polymorphism in TMJ degeneration., (© 2011 Eur J Oral Sci.)

Introduction: Helicobacter pylori infection is an established risk factor for gastric cancer development, but the exact underlying mechanism still remains obscure. The inactivation of tumor suppressor genes such as p53 and p27(KIP1) is a hypothesized mechanism, although there is no consensus regarding the influence of H. pylori cagA(+) in the development of these genetic alterations., Goals: To verify the relationship among H. pylori infection, p53 mutations and p27(Kip1) Protein (p27) expression in gastric adenocarcinomas (GA) seventy-four tissues were assayed by PCR for H. pylori and cagA presence. Mutational analysis of p53 gene was performed by single-strand conformation polymorphism (SSCP). Seventy tissues were analyzed by an immunohistochemical method for p27 expression., Results: From the samples examined, 95% (70/74) were H. pylori positive, 63% cagA(+). Altered p53 electrophoretic mobility was found in 72% of cases and significantly more frequent in the presence of cagA. Considerable reduction in p27 expression (19%) was found with a tendency for association between cagA(+) and p27(-), although the results were not statistically significant. Concomitant alterations of both suppressor genes were detected in 60% of cases. In the cases cagA(+), 66.7% of them had these concomitant alterations., Conclusions: The data suggest that H. pylori cagA(+) contributes to p53 alteration and indicate that concomitant gene inactivation, with reduced p27 expression, may be a mechanism in which H. pylori can promote the development and progression of gastric cancer., (Copyright © 2010 Elsevier Ltd. All rights reserved.)