Dynamics and features of transmission clusters of HIV-1 subtypes in the state of São Paulo, Brazil.

Background: Molecular epidemiology techniques allow us to track the HIV-1 transmission dynamics. Herein, we combined genetic, clinical and epidemiological data collected during routine clinical treatment to evaluate the dynamics and characteristics of transmission clusters of the most prevalent HIV-1 subtypes in the state of São Paulo, Brazil. Methods: This was a cross-sectional study conducted with 2,518 persons living with HIV (PLWH) from 53 cities in São Paulo state between Jan 2004 to Feb 2015. The phylogenetic tree of protease/reverse transcriptase (PR/RT) regions was reconstructed by PhyML and ClusterPicker used to infer the transmission clusters based on Shimodaira-Hasegawa (SH) greater than 90% (phylogenetic support) and genetic distance less than 6%. Results: Of a total of 2,518 sequences, 2,260 were pure subtypes at the PR/RT region, being B (88%), F1 (8.1%), and C (4%). About 21.2% were naïve with a transmitted drug resistance (TDR) rate of 11.8%. A total of 414 (18.3%) of the sequences clustered. These clusters were less evident in subtype B (17.7%) and F1 (15.1%) than in subtype C (40.2%). Clustered sequences were from PLWH at least 5 years younger than non-clustered among subtypes B (p < 0.001) and C (p = 0.037). Men who have sex with men (MSM) predominated the cluster in subtype B (51%), C (85.7%), and F1 (63.6%; p < 0.05). The TDR rate in clustered patients was 15.4, 13.6, and 3.1% for subtypes B, F1, and C, respectively. Most of the infections in subtypes B (80%), C (64%), and F1 (59%) occurred within the state of São Paulo. The metropolitan area of São Paulo presented a high level of endogenous clustering for subtypes B and C. The São Paulo city had 46% endogenous clusters of subtype C. Conclusion: Our findings showed that MSM, antiretroviral therapy in Treatment-Naive (ART-naïve) patients, and HIV1-C, played an important role in the HIV epidemic in the São Paulo state. Further studies in transmission clusters are needed to guide the prevention intervention.

Immune-mediated hepatitis: Basic concepts and treatment.

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized advanced cancer management. Nevertheless, the generalized use of these medications has led to an increase in the incidence of adverse immune-mediated events and the liver is one of the most frequently affected organs. Liver involvement associated with the administration of immunotherapy is known as immune-mediated hepatitis (IMH), whose incidence and clinical characteristics have been described by different authors. It often presents as mild elevations of amino transferase levels, seen in routine blood tests, that spontaneously return to normal, but it can also manifest as severe transaminitis, possibly leading to the permanent discontinuation of treatment. The aim of the following review was to describe the most up-to-date concepts regarding the epidemiology, diagnosis, risk factors, and progression of IMH, as well as its incidence in different types of common cancers, including hepatocellular carcinoma. Treatment recommendations according to the most current guidelines are also provided.

Assessment of Serum sRANKL, sRANKL/OPG Ratio, and Other Bone Turnover Markers with the Estimated 10-Year Risk of Major and Hip Osteoporotic Fractures in Rheumatoid Arthritis: A Cross-Sectional Study.

BACKGROUND: Fracture risk assessment tool (FRAX) index was developed for estimating of the 10-year risk of major or hip osteoporotic fracture. To date, there is insufficient information regarding the correlation between FRAX and serum bone turnover markers (BTMs), such as soluble ligand of receptor activator of nuclear factor-κB (sRANKL), osteoprotegerin (OPG), and other molecules related with secondary osteoporosis in rheumatoid arthritis (RA). Therefore, this study is aimed at assessing the correlation between the FRAX and serum levels of sRANKL, OPG, sRANKL/OPG ratio, Dickkopf-1 (DKK-1), and sclerostin (SOST) in RA. METHODS: Cross-sectional study included 156 postmenopausal women with RA. Bone mineral density (BMD) was measured at lumbar spine (L1-L4) and total hip using dual-energy X-ray absorptiometry (DXA). RA patients were divided into (A) RA + osteoporosis and (B) RA without osteoporosis. FRAX scores were calculated including the total hip BMD. Serum sRANKL, OPG, DKK-1, and SOST levels were measured by ELISA. Pearson tests were used for assessing the correlation between serum levels of these molecules and FRAX scores in RA. RESULTS: The RA + osteoporosis group had elevated sRANKL levels (p = 0.005), higher sRANKL/OPG ratio (p = 0.017), decreased DKK-1 (p = 0.028), and lower SOST levels (p < 0.001). Low total hip BMD correlated with high sRANKL (p = 0.001) and sRANKL/OPG ratio (p = 0.005). Total hip and lumbar spine BMD correlated with DKK-1 (p = 0.009 and p = 0.05, respectively) and SOST levels (p < 0.001 and p < 0.001, respectively). Higher sRANKL levels and sRANKL/OPG ratio correlated with estimated 10-year risk of a major osteoporotic fractures (p = 0.003 and p = 0.003, respectively) and hip fracture (p = 0.002 and p = 0.006, respectively). High serum SOST levels were associated with a low estimated 10-year risk of a major osteoporotic fracture (p = 0.003) and hip fracture (p = 0.009). CONCLUSION: High sRANKL levels and sRANKL/OPG ratio can be useful to detect a subgroup of RA patients who has an increased 10-year risk of major and hip osteoporotic fractures.

Consensus of the Spanish society of laboratory medicine and the Spanish society of medical oncology on the methodology and criteria for evaluation of circulating tumour markers in breast cancer.

The measurement of circulating tumour markers (TMs) for the diagnosis or monitoring of breast cancer has sometimes been considered of limited utility. In addition to the overinterpretation of irrelevant changes in marker levels, the characteristics of the patient, the disease or other pathologies that can modify them are often not considered in their evaluation. On the other hand, there are recent data on the relationship of TMs with molecular subtypes and on their prognostic value, the knowledge of which may improve their clinical utility. This consensus article arises from a collaboration between the Spanish Society of Laboratory Medicine (SEQCML) and the Spanish Society of Medical Oncology (SEOM). It aims to improve the use and interpretation of circulating TMs in breast cancer. The text summarizes the current knowledge and available evidence on the subject and proposes a series of recommendations mainly focussed on the indication, the frequency of testing and the factors that should be considered for correctly interpreting changes in the levels of TMs.

Peficitinib hydrobromide to treat rheumatoid arthritis.

Peficitinib hydrobromide is a small Janus kinase inhibitor (JAK1, JAK2, JAK3 and TYK2) molecule for the treatment of rheumatoid arthritis (RA). Phase II and phase III clinical trials and extension studies with different doses have been conducted to assess the drug's efficacy and safety with substantially improved outcomes observed in RA. This JAK inhibitor oral drug demonstrated clinical response as once-daily monotherapy in patients with moderate to severe RA, also in combination with methotrexate (MTX), who had an inadequate response to MTX. The findings from studies of this new JAK inhibitor have shown that, both in monotherapy as well as in combination with conventional synthetic disease-modifying antirheumatic drugs (csDMARDs), it has efficacy, safety and tolerability in RA patients.

Ex vivo expansion of regulatory T cells from long-term Belatacept-treated kidney transplant patients restores their phenotype and suppressive function but not their FOXP3 TSDR demethylation status.

We recently reported that Tregs from long-term Belatacept-treated kidney transplant patients displayed an altered phenotype and impaired suppressive function compared to Tregs from healthy controls. However, it remains unknown whether ex vivo expansion of Tregs from patients who underwent long-term immunosuppression may be feasible to be used in their treatment. In this work, Tregs from Belatacept-treated patients were polyclonally expanded in vitro in the presence of rapamycin and IL-2. After four weeks of expansion, Tregs from patients expressed high levels of FOXP3, CD25, CTLA-4, Helios and CCR7, and showed strong suppressive activity, even in the presence of pro-inflammatory cytokines. However, FOXP3 TSDR demethylation remained lower in expanded Tregs from Belatacept-treated patients compared to healthy control Tregs. These data suggest that ex vivo expansion of Tregs from patients undergoing long-term immunosuppression may require the use of epigenetic modifying agents to stabilize FOXP3 expression to be considered as treatment in kidney transplant patients.

Nanoscale mapping of chemical composition in organic-inorganic hybrid perovskite films.

Lead-based organic-inorganic hybrid perovskite (OIHP) solar cells can attain efficiencies over 20%. However, the impact of ion mobility and/or organic depletion, structural changes, and segregation under operating conditions urge for decisive and more accurate investigations. Hence, the development of analytical tools for accessing the grain-to-grain OIHP chemistry is of great relevance. Here, we used synchrotron infrared nanospectroscopy (nano-FTIR) to map individual nanograins in OIHP films. Our results reveal a spatial heterogeneity of the vibrational activity associated to the nanoscale chemical diversity of isolated grains. It was possible to map the chemistry of individual grains in CsFAMA [Cs0.05FA0.79MA0.16Pb(I0.83Br0.17)3] and FAMA [FA0.83MA0.17Pb(I0.83Br0.17)3] films, with information on their local composition. Nanograins with stronger nano-FTIR activity in CsFAMA and FAMA films can be assigned to PbI2 and hexagonal polytype phases, respectively. The analysis herein can be extended to any OIHP films where organic cation depletion/accumulation can be used as a chemical label to study composition.

Extrahepatic complications of non-alcoholic fatty liver disease: Its impact beyond the liver. / Complicaciones extrahepáticas de la enfermedad por hígado graso no alcohólico: impacto más allá del hígado.

Non-alcoholic fatty liver disease (NAFLD) is currently one of the main causes of chronic liver disease in Western countries, with a 25% prevalence reported in the general population worldwide. Visceral adiposity and liver fat promote a state of systemic inflammation, predisposing individuals with NAFLD to the extrahepatic pathologies of cardiovascular disease (the most common cause of death in patients with NAFLD), diabetes mellitus, chronic kidney disease, hypothyroidism, polycystic ovary syndrome, obstructive sleep apnea, and an increased risk for presenting with gastrointestinal and extraintestinal neoplasias. Different mechanisms between NAFLD and its association with extrahepatic diseases have been reported, and lipotoxicity is the main cause of inflammatory pathway activation that results in extrahepatic tissue damage.

Quality of life in elderly breast cancer patients with localized disease receiving endocrine treatment: a prospective study.

PURPOSE: In this paper we study the quality of life (QoL) of elderly breast cancer patients receiving endocrine treatment (ET). More QoL data on elderly patients treated with ET are needed. Our aims are to study QoL in early-stage breast cancer patients throughout the treatment period and compare the QoL of ET groups. METHODS: 148 patients > 65 years who began ET with either tamoxifen or aromatase inhibitor (AI) completed the EORTC QLQ-C30 and QLQ-BR23 and the Interview for Deterioration in Daily Living Activities in Dementia (IDDD) questionnaires three times over 3 years of ET. Linear mixed-effect models were used to evaluate longitudinal QoL changes. ET group comparisons were conducted after 3 years of treatment via ANCOVA adjusted by basal QoL. RESULTS: QoL scores were high (> 80/100 points) in most QoL areas, with moderate limitations (> 30) in sexual functioning and enjoyment and in future perspective. After 3 years of ET, four QoL areas improved (< 6 points) compared to baseline and 3-month assessments. Hot flushes worsened (8 points) at the 3-month assessment but by 3 years had recovered. AI patients showed more hot flushes, pain and diarrhea and less sexual enjoyment than tamoxifen patients after 3 years of ET (differences 3-12 points). CONCLUSIONS: Results indicate that elderly early-stage breast cancer patients adapted well to their disease and ET treatment over the 3 years. Few QoL differences were observed between ET groups.

SEOM clinical guidelines on cardiovascular toxicity (2018).

One of the most common side effects of cancer treatment is cardiovascular disease, which substantially impacts long-term survivor's prognosis. Cardiotoxicity can be related with either a direct side effect of antitumor therapies or an accelerated development of cardiovascular diseases in the presence of preexisting risk factors. Even though it is widely recognized as an alarming clinical problem, scientific evidence is scarce in the management of these complications in cancer patients. Consequently, current recommendations are based on expert consensus. This Guideline represents SEOM's ongoing commitment to progressing and improving supportive care for cancer patients.

Serum P-glycoprotein level: a potential biomarker of DMARD failure in patients with rheumatoid arthritis.

OBJECTIVES: To evaluate the utility of elevated serum P-glycoprotein (P-gp) as a risk marker of therapeutic response failure in rheumatoid arthritis (RA) patients treated with disease-modifying antirheumatic drugs (DMARDs). METHODS: A cross-sectional study was conducted in 151 RA patients. Patients were classified into two groups according to the response achieved in terms of the disease activity score (DAS)28 after ≥ 6 months: (1) patients with a therapeutic response to DMARDs, with DAS28 < 3.2; and (2) patients without a response to DMARDs, with persistent DAS28 ≥ 3.2. We explored a wide group of clinical factors associated with therapeutic resistance. Serum P-gp levels were measured by ELISA. The risk of P-gp elevation as a marker of failure to achieve a therapeutic response to DMARDs was computed using multivariate logistic regression. RESULTS: Serum P-gp levels were significantly higher in RA patients (n = 151) than in the controls (n = 30) (158.70 ± 182.71 ng/mL vs. 14.12 ± 8.97 ng/mL, p < 0.001). The P-gp level was correlated with the DAS28 score (r = 0.39, p < 0.001). RA patients with DMARD failure had higher serum P-gp levels than patients with a therapeutic response (206 ± 21.47 ng/mL vs 120.60 ± 15.70 ng/mL; p = 0.001). High P-gp levels increased the risk of DMARD failure (OR 3.36, 95% CI 1.54-7.27, p = 0.001). After adjusting for confounding variables, elevated P-gp remained associated with DMARD failure (OR 2.64, 95% CI 1.29-5.40, p = 0.01). CONCLUSION: Elevated serum P-gp is associated with DMARD failure. The P-gp level can be considered a clinical tool for evaluating the risk of DMARD failure in patients; however, future prospective studies should be performed to evaluate the utility of this marker in predicting long-term responses.

Association of Ischemic Cardiovascular Disease with Inadequacy of Liver Store of Retinol in Elderly Individuals.

OBJECTIVE: Vitamin A antioxidant role has an important relationship with the metabolic processes of aging and cardiovascular disease (CVD). This study aimed at assessing the liver store of retinol in elderly individuals who died from cardiovascular disease and its relationship with liver weight and body weight. METHODS AND RESULTS: This is a cross-sectional study conducted in necropsied individuals, aged 60 years or over, until 48 hours postmortem. The study assessed 65 elderly individuals who died from ischemic heart diseases (G1), cerebrovascular diseases (G2), other forms of heart disease (G3), or infectious heart diseases (G4). Twenty percent had inadequate liver store of retinol. G1 showed lower median of liver store of retinol when compared to G3 (p < 0.001), and G3 showed the highest median when compared to G2 (p = 0.007). A significant association was observed between inadequate liver store of retinol and death by ischemic CVD (G1) (p = 0.001) with an odds ratio of 10.38. It was observed that individuals with higher body weight and liver weight showed lower liver store of retinol with significant differences (p = 0.027 and p = 0.026). CONCLUSION: Ischemic CVD and increased body weight and liver weight are related to a greater impairment of the liver store of retinol.

The 3'-UTR (CA)n microsatellite on CD40LG gene as a possible genetic marker for rheumatoid arthritis in Mexican population: impact on CD40LG mRNA expression.

The objective of this study was to determine the association of the CD40LG 3'-UTR (CA)n microsatellite with rheumatoid arthritis (RA) and CD40LG mRNA levels in females from western Mexico. A case-control study with 219 RA patients and 175 control subjects (CS) was conducted. Genotyping was performed by polymerase chain reaction (PCR), X 2 test was used to compare genotype and allele frequencies, and odds ratios and 95% confidence intervals were calculated to evaluate the association between RA and the microsatellite. CD40LG mRNA expression was assessed by real-time quantitative PCR. For comparisons between groups, Kruskal-Wallis or Mann-Whitney U tests for non-parametric data and ANOVA test for parametric data were performed. Among the 13 different alleles identified, CA25 was the most represented (45.4% RA and 46.3% CS). Stratification according to CA repeats as CA25 showed a tendency towards a higher frequency of >CA25 alleles in RA patients (29%) compared to CS (23.4%). There was no association between any genotype and the clinical parameters of RA patients. According to the 2-∆∆Cq method, CD40LG mRNA expression in RA patients was 4.5-fold higher compared to CS; this difference was significant when assessed by the 2-∆Cq method (p = 0.028). Compared to carriers of the CA25/CA25 genotype, CS carrying the CA25/>CA25 carriers. The 3'-UTR CD40LG (CA)n microsatellite is not a genetic marker for RA in western Mexican population; however, results suggest that it plays a role in the CD40LG mRNA expression.

Prevalencia de Malassezia spp en pacientes con diabetes mellitus tipo 2 de acuerdo con el control glucémico / Prevalence of Malassezia spp in type 2 diabetes mellitus according to glycemic control

Resumen ANTECEDENTES: Malassezia spp es un saprófito de la piel, relacionada con diversas afecciones cutáneas, se ha reportado frecuencia elevada en pacientes con inmunosupresión. OBJETIVO: determinar la prevalencia de Malassezia spp en individuos con diabetes mellitus tipo 2 de acuerdo con el control glucémico. MATERIAL Y MÉTODO: estudio abierto, observacional, descriptivo y transversal, efectuado en pacientes voluntarios que participaron en la 24ª Carrera Nacional del Paciente con Diabetes el 15 de octubre de 2016 en la Ciudad de México, en quienes se realizó toma de glucemia capilar preprandial y hemoglobina glicosilada, así como pesquisa de Malassezia spp mediante frotis de la región malar, teñido con azul de metileno. RESULTADOS: se incluyeron 49 pacientes con diabetes mellitus tipo 2; hubo predominio de 31 pacientes sin buen control glucémico (67%) en comparación con 16 pacientes controlados (33%). Los frotis con levaduras escasas (+) estuvieron presentes en 21 (59%) pacientes sin control y en 7 (41%) pacientes con control; los frotis con cantidad de levaduras moderada (++) se observaron en 7 (74%) pacientes sin control y en 5 (26%) pacientes con control; los frotis con levaduras abundantes estuvieron presentes en 7 (63%) pacientes sin control y en 2 (37%) pacientes con control. CONCLUSIÓN: en nuestro estudio la prevalencia de Malassezia spp en pacientes con diabetes mellitus tipo 2 fue del 100%, con menor número de levaduras en los que tenían control glucémico adecuado, lo que puede indicar que la posibilidad de tener esta levadura aumenta con el descontrol glucémico y probablemente denota el grado de inmunosupresión en estos pacientes.

Abstract BACKGROUND: Malassezia spp is a saprophyte of the skin, related to diverse cutaneous affections, and has been reported a high frequency in patients with immunosuppression. OBJECTIVE: To determine the prevalence of Malassezia spp in individuals with type 2 diabetes mellitus according to glycemic control. MATERIAL AND METHOD: An open, observational, descriptive and cross-sectional study was performed in volunteer patients who participated in the 24th National March of the Patient with Diabetes in Mexico City on October 15, 2016; where preprandial capillary glycemia and glycosylated hemoglobin were taken. We took a scraping of the malar region skin to find Malassezia spp, smears stained with methylene blue. RESULTS: A total of 49 patients with type 2 diabetes mellitus were included; there were a predominance of 31 patients without glycemic control (67%) in comparison with 16 controlled patients (33%). Smears with low yeast (+) were present in 21 (59%) uncontrolled patients and in 7 (41%) controlled patients; smears with a moderate amount of yeast (++) were present in 7 (74%) uncontrolled patients and in 5 (26%) controlled patients; smears with abundant yeasts were present in 7 (63%) uncontrolled patients and in 2 (37%) controlled patients. CONCLUSION: In our study the prevalence of Malassezia spp in patients with type 2 diabetes mellitus was of 100%, with a lower number of yeasts in patients with adequate glycemic control; this can indicate that the possibility of presenting this yeast increases with bad glycemic control and probably denotes the degree of immunosuppression in these patients.

Efecto de Microemulsiones de Aceites Esenciales Sobre el Eritrocito Humano y Bacterias Patógenas / Effect of Microemulsions of Essential Oils on Human Erythrocyte and Pathogens Bacteria

RESUMEN: El objetivo del presente trabajo fue evaluar el efecto de las microemulsiones de aceite esencial de romero (AER) y árbol de té (AET) sobre el eritrocito humano y microorganismos patógenos. Para ello, se elaboraron microemulsiones de AER y AET al 8.0% (v/v), 5.0% (v/v) y 2.5% (v/v). Las microemulsiones fueron probadas sobre el eritrocito humano para determinar el porcentaje de hemólisis, el porcentaje de inhibición de hemólisis y su actividad antibacterial contra E. coli O157:H7 y S. aureus. Las microemulsiones con AER no presentaron actividad hemolítica significativa, caso contrario con las microemulsiones de AET al 8.0% (≈70%) y 5.0% (33%) que presentaron mayor actividad hemolítica. Las microemulsiones de AER protegieron significativamente al eritrocito contra la presencia de radicales libres, en comparación con aquellas de AET (p< 0.05). Además, las emulsiones de AET al 8.0% mostraron efectos antibacterianos contra E. coli O157:H7 y S. aureus mientras que AER al 8.0% solo mostraron efecto contra E. coli O157:H7. La limitante del estudio fue que no utilizamos células nucleadas para establecer si los aceites esenciales dañan el material nuclear. Sin embargo, observamos que el tipo y la cantidad de aceite utilizado pueden tener implicaciones serias sobre la membrana eritrocitaria. Se concluye que las microemulsiones de AER presentaron mejor efecto protector eritrocitario, mientras que las microemulsiones de AET presentaron mejor actividad antibacterial contra las bacterias estudiadas, pero con mayor efecto tóxico sobre el eritrocito.

ABSTRACT: The aim of the study was to evaluate the effect of microemulsions of rosemary (AER) and tea tree (AET) essential oils on human erythrocyte and pathogen bacteria. Microemulsions of each oil were prepared at 8.0% (v/v), 5.0% (v/v) and 2.5% (v/v), and they were tested on human erythrocyte to determine the hemolysis percentage, hemolysis inhibition percentage and the antibacterial capacity against E. coli O157:H7 and S. aureus. All AER microemulsions showed no significant hemolytic activity. On the contrary, AET microemulsions showed hemolytic effect but those in concentrations of 8.0% (≈70 %) and 5.0% (33%) showed the highest effect. In addition, AER microemulsions showed protective effect against free radicals in comparison with the AET microemulsions (p< 0.05). On the other hand, the AET microemulsion at 8.0% showed antibacterial effect against E. coli O157:H7 and S. aureus, and the AER at 8.0% showed antibacterial effect against E. coli O157:H7. The limitation of this study was that nucleated cells were not used to observe the damage of the essential oils on nuclear material. However, the observed damage of erythrocyte's membrane is depending on type and amount of used oil. Therefore, it can be concluded that the AER microemulsions showed better protective effect of erythrocytes, while AET microemulsions showed better antibacterial effect against the tested bacteria, although with toxic effect on the erythrocytes.

Impact of optimal anticoagulation therapy on chronic venous ulcer healing in thrombophilic patients with post-thrombotic syndrome.

OBJECTIVE: Post-thrombotic syndrome (PTS) is the long-term sequelae of deep venous thrombosis (DVT). PTS clinical manifestations include chronic leg pain, oedema, lipodermatosclerosis and ulcers. The objective of this study is to determine in patients with documented history of thrombophilias and DVT whether the number of previous thrombotic events and optimal anticoagulation therapy are associated with the time to venous ulcer healing following the start of compression therapy. METHOD: Retrospective analysis performed in thrombophilic patients under the age of 50 years old with chronic venous ulcers secondary to DVT at the wound clinic in the National Institute of Medical Sciences and Nutrition 'Salvador Zubirán ' in Mexico City. Variables such as the number or episodes of thrombotic events, type of hypercoagulable disorder, optimal anticoagulation therapy with Warfarin monitored by therapeutic International Normalised Ratio (INR) (2-3) and compliance to compression therapy were examined. Patients that underwent superficial or perforator vein interruption or endovascular recanalisation of deep veins were excluded from the study. RESULTS: From a database of 29 patients with chronic venous ulcers followed in our clinic from January 1992 to September 2012, only 13 patients (61% female) met the inclusion criteria. Mean age±standard deviation (SD) was 32±12 years old. Of these, seven (54%) patients with suboptimal INR presented with an average of two previous thrombotic events and the remaining six (46%) patients with optimal INR only one event (p=0.28), the mean time to the clinical manifestation of a venous ulcer after the first episode of DVT was 39 months (range: 12-72) for patients with suboptimal INR and 82 months (range: 12-216) for those with optimal anticoagulation therapy (p=0.11). During the mean follow-up period of 52 months, all patients in optimal anticoagulation healed their ulcer; their mean time for wound healing was 44 months (range: 4-102). In the suboptimal INR group, only four healed the ulcers with an mean of 72 months (range: 2-204) (p=0.94). CONCLUSION: There seems to be an association between an optimal anticoagulation therapy with Warfarin monitored by INR and wound healing rates in thrombophilic patients with chronic venous ulcers. Further research is warranted. DECLARATION OF INTEREST: The authors have no conflict of interest.

CD40 functional gene polymorphisms and mRNA expression in rheumatoid arthritis patients from western Mexico.

The CD40 pathway is involved in the development and pathogenesis of autoimmune diseases, including rheumatoid arthritis (RA). Two single nucleotide polymorphisms (SNPs) in the CD40 gene, rs1883832 and rs4810485, are associated with susceptibility to inflammatory and autoimmune diseases and are thought to alter CD40 expression at the mRNA and protein level. This study assessed for the first time the association of these SNPs with RA and CD40 mRNA levels in a western Mexican population. A total of 278 RA patients and 318 control subjects were included. Genotyping was performed by polymerase chain reaction (PCR)-restriction fragment length polymorphism, and CD40 mRNA expression was determined by real-time quantitative PCR. No significant differences in genotype and allele frequencies were identified between the RA patients and controls. When stratified by genotype, these SNPs were not found to be associated with the presence of autoantibodies or the clinical activity of the disease. CD40 mRNA levels were elevated 1.5-fold in RA patients compared to control subjects; however, no clear tendencies were observed following stratification by genotype. These results suggest that the CD40 SNPs rs1883832 and rs4810485 are not RA susceptibility markers in the western Mexican population. Further studies are needed to clarify their roles in CD40 mRNA expression.

SEOM Clinical Guideline of fertility preservation and reproduction in cancer patients (2016).

Chemotherapy and radiotherapy often result in reduced fertility in cancer patients. With increasing survival rates, fertility is an important quality-of-life concern for many young cancer patients. Around 70-75% of young cancer survivors are interested in parenthood but the numbers of patients who access fertility preservation techniques prior to treatment are significantly lower. Moreover, despite existing guidelines, healthcare professionals do not address fertility preservation issues adequately. There is a critical need for improvements in clinical care to ensure patients are well informed about infertility risks and fertility preservation options and to support them in their reproductive decision-making prior to cancer treatment.

Effects of high-energy ultrasound on the functional properties of proteins.

In recent years, high-energy ultrasound has been used as an alternative to improve the functional properties of various proteins, such as from milk, eggs, soy and poultry. The benefits of implementing this technology depend on the inherent characteristics of the protein source and the intensity and amplitude of the ultrasound, as well as on the pH, temperature, ionic strength, time, and all of the variables that have an effect on the physicochemical properties of proteins. Therefore, it is necessary to establish the optimal conditions for each type of food. The use of ultrasound is a promising technique in food technology with a low impact on the environment, and it has thus become known as a green technology. Therefore, this review focuses on the application of high-energy ultrasound to food; its effects on the functional properties of proteins; and how different conditions such as the frequency, time, amplitude, temperature, and protein concentration affect the functional properties.