Challenges of diagnosing homologous recombination deficiencies in metastatic prostate cancer: a six-year experience from a single institution.

PURPOSE: We evaluated the prevalence of homologous recombination deficiencies (HRD) to determine the efficacy of different techniques and clinical characteristics of patients. METHODS: This retrospective study included patients with metastatic prostate cancer who underwent molecular testing at our hospital between 2016 and 2022. We used tumor tissue, ctDNA, and lymphocytes for somatic or germline testing. We analyzed the clinical characteristics and survival outcomes. RESULTS: 144 patients were tested (113 somatic, 21 germline, and 10 both). Technical issues prevented the analysis of 23 prostatic samples (18.7%). 12 (8.3%) patients had HRD. BRCA2 was the most frequent mutation (66.7%). Patients with HRD were younger (57.5 years). Patients with BRCA mutations had poorer survival (31.9 vs 56.3 months, p = 0.048). CONCLUSION: In our institution, 8.3% of the patients had HRD. Tumor tissue analysis failed in 18.7% of tests. ctDNA analysis is an alternative detection method. BRCA mutations are correlated with poor prognosis.

Treatment Patterns and Survival Outcomes Before and After Access to Immune Checkpoint Inhibitors for Patients With Metastatic Urothelial Carcinoma: A Single-Center Retrospective Study From 2004 to 2021.

INTRODUCTION: Metastatic urothelial carcinoma (mUC) is a lethal disease with limited treatment options. We aimed to compare the treatment patterns and outcomes of patients with mUC who were treated before and after the introduction of immune checkpoint inhibitors (ICIs) at a tertiary hospital in Barcelona. METHODS: Single-center retrospective study from 2004 to 2021. Access to ICIs began in December 2014. We analyzed differences in clinical characteristics and survival outcomes, such as overall survival (OS), progression-free survival (PFS), and restricted mean survival time (RMST). RESULTS: A total of 206 patients were included. The median follow-up was 48.6 months. Ninety and 116 patients were treated during the pre-ICIs and the post-ICIs eras, respectively. We found high treatment attrition rates, with no differences in the number of patients who received second-line (48%) and third-line (26%) therapies between the two eras. In the second-line, ICIs became the predominant therapy (58%), leading to a 30% reduction in the utilisation of platinum-based ChT and non-platinum ChT. Innovative approaches including ICIs in the first-line treatment (18%) and targeted therapies in the third-line setting (34%) were observed. We found no differences in the median OS, 2-year OS, or 24-month RMST between the two periods. CONCLUSION: ICIs have emerged as a transformative treatment option, reshaping the treatment landscape. Nevertheless, substantial attrition rates from first-line to subsequent lines of systemic therapies might impede the potential impact of ICIs on long-term survival outcomes across the entire population.

Cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage I seminoma treated with a risk-adapted strategy: a Spanish single-centre retrospective analysis.

PURPOSE: To describe the incidences of hypogonadism, hypertension, and dyslipidaemia in patients with stage 1 seminoma (S1S) testicular cancer (TC) treated with a risk-adapted strategy. METHODS: A retrospective analysis from 2000 to 2020 was conducted. Active surveillance (AS), carboplatin one cycle, and carboplatin two cycles were offered according to risk factors. Cumulative incidences and relapse-free survival (RFS) were estimated. RESULTS: Of the 145 patients, 8 (5.4%) were excluded due to bilateral TC or hypogonadism at diagnosis. Median follow-up time was 8.2 years. Eighty-four, 30, and 33 patients were treated with AS, carboplatin one cycle, and carboplatin two cycles, respectively. In the overall population, the 5-year and 10-year cumulative incidences were 1.6% and 5.3% for hypogonadism; 2.0% and 8.6% for hypertension; and 12.4% and 25.1% for dyslipidaemia. No statistically significant differences were found in the incidences among the three adjuvant strategies. Five-year and 10-year RFS were 85.9% and 83.3% for AS; 92.4% and 84.0% for carboplatin one cycle; and 96.7% at both times for carboplatin two cycles. CONCLUSION: There were no statistically differences in cumulative incidences of hypogonadism, hypertension, and dyslipidaemia in S1S patients treated with a risk-adapted strategy.

Jorge clinical study: 10-year outcomes of risk-adapted radiotherapy defined by multiparametric MRI for prostate cancer.

PURPOSE: To analyze the 10-year biochemical relapse-free survival (BRFS), locoregional relapse-free survival (LRFS), metastasis-free survival (MFS), and overall survival (OS) in patients diagnosed with localized prostate adenocarcinoma treated with radiotherapy (RT) ± androgen deprivation therapy (ADT), according to the risk groups based on multiparametric magnetic resonance imaging (mpMRI) instead of digital rectal exam (DRE). METHODS: We retrospectively evaluated 140 consecutive patients diagnosed with localized prostate adenocarcinoma, stratified into different risk groups-low (LR), intermediate (IR), and high (HR) by mpMRI results. RESULTS: After a median follow-up of 104 months, in LR group (n = 15), 10-year BRFS was 86.7%, 10-year LRFS was 86.7%, 10-year MFS was 93.3%, and 10-year OS was 100%. In IR group (n = 80), 10-year BRFS was 80.5%, 10-year LRFS was 86.1%, 10-year MFS was 92.6%, and 10-year OS was 76%. In HR group (n = 45), 10-year BRFS was 72.8%, 10-year LRFS was 78.7%, 10-year MFS was 82.1%, and 10-year OS was 77% (2 deaths from prostate cancer). According to mpMRI results, 36 (25.7%) patients change the risk group and 125 (89.28%) patients change the TNM stage. There was a trend for higher metastatic relapse in patients who switched from IR to HR (due to mpMRI) versus the patients who remained in the IR (20%, vs. 1.81% p = 0.059). Multivariate analysis showed that locoregional relapse was strongly associated with distant relapse (OR = 9.28; 95%CI: 2.60-33.31). There were no cases of acute grade 3 toxicity. Late grade 3 genitourinary, gastrointestinal, and sexual toxicity were 2.8%, 0.7%, and 1.2%, respectively. CONCLUSION: This is the first study with a 10-year median follow-up of patients diagnosed with localized prostate cancer treated with radiotherapy according to the risk groups established by mpMRI. Our findings show that mpMRI is a key tool to diagnose and establish risk groups in these patients, to optimize their treatment.

La función de las proteínas de choque térmico en las infecciones virales / The Role of Heat Shock Proteins in Viral Infections

Resumen Las proteínas de choque térmico se describieron como una respuesta intracelular al estrés calórico; sin embargo, al paso del tiempo, se observó que estas proteínas tienen múltiples funciones y que participan de manera relevante tanto en los procesos fisiológicos como patológicos. Las actividades que realizan las proteínas de choque térmico se relacionan con su localización, que puede ser intra o extracelular, al momento fisiológico y a las diferentes asociaciones estructurales, que pueden ser desde péptidos derivados de estas, hasta dímeros o multímeros. Con base en estas características funcionales, se les ha denominado proteínas multiempleo o "moonlighting proteins". En este artículo se describen algunas de las actividades de estas proteínas con relación al sistema inmunológico y las infecciones virales, en particular con los procesos inflamatorios.

Abstract Heat shock proteins (HSP) were first described as a cell response to heat stress. However, over time, it has become clear they have multiple functions inside and outside cells, and that they actively participate in different physiological and pathological processes. They perform functions related to their cellular location or physiological moment, which is why they have been called multi-use proteins or "moonlighting proteins". Furthermore, HSP activity is associated with different structural conformations, from peptides derived from them or as dimers or multimers, to mention a few. This article describes these functions and their relationship with the immune system, and their relationship with viral infection, particularly with inflammatory processes.

HCV spontaneous clearers showed low senescence profile in people living with HIV under long ART.

Coinfection with hepatitis C virus (HCV) and human immunodeficiency virus (HIV) increases immune activation, inflammation, and oxidative stress that could lead to premature senescence. Different HCV infections, either acute or chronic infection, could lead to distinct premature cellular senescence in people living with HIV (PLWHIV). Observational study in 116 PLWHIV under antiretroviral treatment with different HCV status: (i) n = 45 chronically infected with HCV (CHC); (ii) n = 36 individuals who spontaneously clarify HCV (SC); (iii) n = 35 HIV controls. Oxidative stress biomarkers were analyzed at lipid, DNA, protein, and nitrates levels, as well as antioxidant capacity and glutathione reductase enzyme. Replicative senescence was evaluated by relative telomere length (RTL) measurement. Additionally, 26 markers of Senescence-Associated Secretory Phenotype (SASP) were analyzed by multiplex immunoassays (Luminex xMAP technology). Differences were evaluated by generalized linear model (GLMs) adjusted by most significant covariates. The SC group had a senescence signature similar to the HIV control group and slightly lower SASP levels. However, significant differences were observed with respect to the CHC group, where an increase in the nitrate concentration [adjusted arithmetic mean ratio, aAMR = 1.73 (1.27-2.35), p < 0.001, q = 0.009] and the secretion of 13 SASP-associated factors [granulocyte macrophage colony-stimulating factor (GM-CSF), interferon-ß, interleukin (IL)-1ß, IL-2, IL-8, IL-13, tumor necrosis factor (TNF)-α, IL-1α, IL-1RA, IL-7, IL-15, C-X-C motif chemokine ligand 10 (IP-10), stem cell factor (SCF); q < 0.1)] was detected. The CHC group also showed higher values of IL-1α, IP-10, and placental growth factor 1 (PIGF-1) than HIV controls. The SC group showed a slightly lower senescence profile than the HIV group, which could indicate a more efficient control of viral-induced senescence due to their immune strengths. Chronic HCV infection in PLWHIV led to an increase in nitrate and elevated SASP biomarkers favoring the establishment of viral persistence.

Acute beetroot juice reduces blood pressure in young Black and White males but not females.

A complex interplay of social, lifestyle, and physiological factors contribute to Black Americans having the highest blood pressure (BP) in America. One potential contributor to Black adult's higher BP may be reduced nitric oxide (NO) bioavailability. Therefore, we sought to determine whether augmenting NO bioavailability with acute beetroot juice (BRJ) supplementation would reduce resting BP and cardiovascular reactivity in Black and White adults, but to a greater extent in Black adults. A total of 18 Black and 20 White (∼equal split by biological sex) young adults completed this randomized, placebo-controlled (nitrate (NO3-)-depleted BRJ), crossover design study. We measured heart rate, brachial and central BP, and arterial stiffness (via pulse wave velocity) at rest, during handgrip exercise, and during post-exercise circulatory occlusion. Compared with White adults, Black adults exhibited higher pre-supplementation resting brachial and central BP (Ps ≤0.035; e.g., brachial systolic BP: 116(11) vs. 121(7) mmHg, P = 0.023). Compared with placebo, BRJ (∼12.8 mmol NO3-) reduced resting brachial systolic BP similarly in Black (Δ-4±10 mmHg) and White (Δ-4±7 mmHg) adults (P = 0.029). However, BRJ supplementation reduced BP in males (Ps ≤ 0.020) but not females (Ps ≥ 0.299). Irrespective of race or sex, increases in plasma NO3- were associated with reduced brachial systolic BP (ρ = -0.237, P = 0.042). No other treatment effects were observed for BP or arterial stiffness at rest or during physical stress (i.e., reactivity); Ps ≥ 0.075. Despite young Black adults having higher resting BP, acute BRJ supplementation reduced systolic BP in young Black and White adults by a similar magnitude, an effect that was driven by males.

Exploring the moderated role of two psychological programs on sexual pleasure from physical symptoms, body image distortion and emotional problems of Hispanic women with breast cancer.

Decreased sexual pleasure is a common problem in women with breast cancer. The aim of this study was to evaluate the effect of psychoeducation vs. acceptance and commitment therapy to improve sexual pleasure according to the predictive role of physical, cognitive and emotional factors. Results of 139 Hispanic women (Mexico and Spain) diagnosed with breast cancer reveal that only the emotional factor of depression predicts decreased sexual pleasure. Although women who participated in the psychoeducation program presented greater physical symptomatology, body image distortions and emotional distress, the results seem to indicate that psychoeducational guidelines are relevant to improve sexual pleasure in those women who manifest higher levels of previous depression. Future research is required to clarify these issues.

A digital health intervention to improve nutrition and physical activity in breast cancer survivors: Rationale and design of the Cook and Move for Your Life pilot and feasibility randomized controlled trial.

BACKGROUND: The design of a randomized pilot trial evaluating the feasibility of two doses of a digital health intervention promoting changes in nutrition and physical activity in breast cancer (BC) survivors is described. METHODS: Eligible women were adults with history of early-stage breast cancer and > 60 days post-treatment, consumed <5 servings/day of fruits/vegetables and/or engaged in <150 min/week of aerobic moderate-to-vigorous physical activity, and had internet access. Participants were randomized to 6 months of either a "low" (1 session) or "high" (12 sessions) dose digital health intervention. Zoom-delivered sessions focused on improving diet and physical activity through didactic and experiential classes delivered by a registered dietitian, chef, exercise physiologist, and culinary educator. All study participants received weekly motivational texts, a Fitbit, and study website access. Diet, accelerometry, anthropometric, psychosocial, and biospecimen data were collected remotely at baseline and six months. Primary outcome was feasibility measured via accrual rate, adherence, retention, and acceptability. RESULTS: Recruitment began in December 2019, was suspended in March 2020 due to the COVID-19 pandemic, resumed September 2020, and concluded in January 2021. Women were identified from the local BC registry and flyers posted in the oncology clinic. Of 929 women recruited, 321 completed the screening assessment, and of these, 138 were eligible. A total of 74 women were enrolled and randomized to the study. CONCLUSION: BC survivors were successfully enrolled in a digital health nutrition and physical activity intervention. If feasible, this intervention will be tested in larger and more diverse populations of cancer survivors. TRIAL REGISTRATION: ClinicalTrials.govNCT04200482.

Accuracy and Limitations of Sentinel Lymph Node Biopsy after Neoadjuvant Chemotherapy in Breast Cancer Patients with Positive Nodes.

Background: Axillary surgical management in patients with node-positive breast cancer at the time of diagnosis converted to negative nodes through neoadjuvant chemotherapy (NAC) remains unclear. Removal of more than two sentinel nodes (SLNs) in these patients may decrease the false negative rate (FNR) of sentinel lymph node biopsies (SLNBs). We aim to analyse the detection rate (DR) and the FNR of SLNB assessment according to the number of SLNs removed. Methods: A retrospective study was performed from October 2012 to December 2018. Patients with invasive breast cancer who had a clinically node-positive disease at diagnosis and with a complete axillary response after neoadjuvant chemotherapy were selected. Patients included underwent SLNB and axillary lymph node dissection (ALND) after NAC. The SLN was considered positive if any residual disease was detected. Descriptive statistics were used to describe the clinicopathologic features and the results of SLNB and ALND. The DR of SLNB was defined as the number of patients with successful identification of SLN. Presence of residual disease in ALND and negative SLN was considered false negative. Results: A total of 368 patients with invasive breast cancer who underwent surgery after complete NAC were studied. Of them, 85 patients met the eligibility criteria and were enrolled in the study. The mean age at diagnosis was 50.8 years. Systematic lymphadenectomy was performed in all patients, with an average of 10 lymph nodes removed. The DR of SLNB was 92.9%, and the FNR was 19.1. The median number of SLNs removed was 3, and at least, three SLNs were obtained in 42 patients (53.2%). When at least three sentinel nodes were removed, the FNR decreased to 8.7%. Conclusions: In this cohort, the SLN assessment was associated with an adequate DR and a high FNR. Removing three or more SLNs decreased the FNR from 19.1% to 8.7%. Complementary approaches may be considered for axillary lymph node staging after neoadjuvant chemotherapy. The study was approved by our institution's ethics committee (Instituto de Investigacion Sanitaria Hospital 12 de Octubre (imas12), Universidad Complutense de Madrid, Madrid, Spain) (https://clinicaltrials.gov/ct2/show/NCEI:20/0048).

Feasibility of targeted axillary dissection for de-escalation of surgical treatment after neoadjuvant chemotherapy in breast cancer.

BACKGROUND: Targeted axillary dissection, which combines sentinel lymph node biopsy with removal of the proven involved node noted during the staging process, has been shown to improve axillary staging and decrease false negative rates after neoadjuvant chemotherapy in patients with breast cancer. OBJECTIVE(S): The main goal of this study was to assess the ability to identify and remove the clipped node and the false negative rate of targeted axillary dissection. METHODS: We performed a prospective study among patients with biopsy-confirmed nodal metastases who received neoadjuvant chemotherapy. A clip was placed on the sample node prior systemic therapy. After neoadjuvant chemotherapy, all patients underwent sentinel lymph node biopsy (dual tracer), localization and excision of the clipped node and axillary lymph node dissection. The clipped node was preoperatively localized in all cases placing an iodine-125 seed guided by ultrasound. The pathology of the sentinel nodes and clipped node was compared with other nodes. RESULTS: A total of 455 patients with invasive breast cancer were studied. Of the 148 patients with NAC, 32 met the eligibility criteria and were enrolled in the study. Mean age at diagnosis was 52.3 years. Systematic lymphadenectomy was performed in all patients, with an average of 14.3 lymph nodes removed. Detection rate of the clipped node alone was 96.9%, and 100% for targeted axillary dissection. Ability of clipped node alone to predict nodal status showed a FNR of 10,5% while SLNB alone performed by dual tracer and targeted axillary dissection, showed FNRs of 5.3% and 5.0%, respectively. Sentinel lymph nodes matched clipped node in 23 patients (74.2%). CONCLUSION (S): In node positive breast cancer patients, targeted axillary dissection is a reliably approach for axillary staging after neoadjuvant chemotherapy. The preoperative location of the clipped node is mandatory to increase the detection rate and optimize the results of the technique.

Urine 1H-NMR Metabolomics to Discriminate Neurocysticercosis Patients from Healthy Controls: An Exploratory Study.

The diagnosis of neurocysticercosis (NCC) is principally based on neuroimaging (magnetic resonance imaging or computed tomography), instrumentation that is scarcely available in the rural regions where Taenia solium transmission, primarily occurs due to poor sanitation conditions. Immunological assays for antigen or antibody detection complement the neuroimaging approach. However, no field-applicable assays to diagnose viable NCC or to guide the referral of cases for neuroimaging or for appropriate management are available. We performed an exploratory study on urine and serum samples using 1H-nuclear magnetic resonance (NMR)-based metabolomics to discriminate NCC patients (n = 14) from healthy control subjects (n = 22). Metabolic profiles demonstrated a discrimination between the urines of NCC patients and noninfected control subjects with a moderate predictive accuracy (R2 = 0.999, Q2 = 0.434). NMR metabolomics analysis has been proven useful in depicting biomarkers linked to other infectious diseases, various types of cancer, and other disorders. Our results, albeit preliminary, open a door to the development of better methods for detecting NCC through the identification of biomarkers participating in disturbed metabolic pathways.

Diffusion tensor imaging-derived biomarkers performance in glioblastoma tumor regions: exploratory data analysis using zombie plots and diagnostic tests.

INTRODUCTION: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma (GB) regions. OBJECTIVE: To compare the efficacy of GB biomarkers using "zombie plots". METHODS: Retrospective cohort of 29 subjects with GB who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. RESULTS: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. CONCLUSIONS: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.

INTRODUCCIÓN: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. OBJETIVO: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. MÉTODOS: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. RESULTADOS: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. CONCLUSIONES: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.

Desempeño de biomarcadores de las imágenes con tensor de difusión en regiones tumorales del glioblastoma. Análisis exploratorio de datos mediante gráficos de zombie y pruebas de diagnóstico / Diffusion tensor imaging-derived biomarkers performance in glioblastoma tumor regions: exploratory data analysis using zombie plots and diagnostic tests

Resumen Introducción: Han sido reportados 11 biomarcadores de imágenes con tensor de difusión (DTI) en las regiones tumorales del glioblastoma. Objetivo: Comparar la eficacia de biomarcadores de glioblastoma mediante gráficos de zombie, que permiten la comparación simultánea en función de razones de verosimilitud. Métodos: Cohorte retrospectiva de 29 sujetos con glioblastoma a quienes se efectuó resonancia magnética cerebral de 3 T. Los eigenvalores mayor, intermedio y menor de ITD se utilizaron para calcular 11 biomarcadores en cinco regiones tumorales: sustancia blanca de apariencia normal (NAWM), edema proximal y distal, tumoral viable y necrosis. Las tablas de contingencia con resultados verdaderos y falsos positivos y negativos permitieron calcular gráficos de zombie basados en el factor de Bayes y pruebas diagnósticas previamente no reportadas. Resultados: Los biomarcadores DM, AF, q, L, Cl, Cp, AR actúan en la zona óptima para el diagnóstico de NAWM. Las regiones de edema proximal y distal, tejido tumoral que se realza con contraste y necrosis no poseen biomarcadores que las identifiquen en un nivel de rendimiento óptimo. Conclusiones: Los biomarcadores DM, AF, q, L, Cl, Cp, AR discriminan el tejido cerebral normal en la zona óptima, pero el rendimiento de otras regiones tumorales se ubica en las zonas de inclusión diagnóstica, exclusión diagnóstica y mediocre.

Abstract Introduction: Using diffusion tensor imaging (DTI), 11 biomarkers have been reported in different glioblastoma regions. Objective: To compare the efficacy of glioblastoma biomarkers using "zombie plots". Methods: Retrospective cohort of 29 subjects with glioblastoma who underwent 3-Tesla brain magnetic resonance imaging. DTI major, intermediate and minor eigenvalues were used to calculate biomarkers at five tumor regions: normal-appearing white matter (NAWM), proximal and distal edema, tumor tissue and necrosis. Contingency tables with true and false positive and negative results allowed the calculation of zombie plots based on the Bayes factor and previously unreported diagnostic tests. Results: The MD, FA, q, L, Cl, Cp and RA biomarkers had a good performance at the optimal zone for NAWM diagnosis. The proximal and distal edema, enhancing rim and necrosis regions do not have biomarkers that identify them with an optimal performance level. Conclusions: Zombie plots allow simultaneous comparison of biomarkers based on likelihood ratios. MD, FA, q, L, Cl, Cp, RA discriminated NAWM normal brain tissue at the optimal zone, but performance for other regions was at the mediocre, diagnostic inclusion and diagnostic exclusion zones.

Hippocampal Atrophy/Sclerosis Is Associated with Old, Calcified Parenchymal Brain Neurocysticercosis, But Not with More Recent, Viable Infections.

Magnetic resonance images from 197 patients with calcified neurocysticercosis (NCC), 38 with viable NCC and 197 NCC-free healthy rural villagers were evaluated to compare the frequency of hippocampal atrophy/sclerosis (HAS) across these populations. Scheltens' medial temporal atrophy scale was used for hippocampal rating. The median age of the 432 study participants was 46 years (interquartile range, 29-62 years), and 58% were women. Hippocampal atrophy/sclerosis was disclosed in 26.9% patients with calcified NCC, compared with 7.9% in patients with viable NCC and 8.1% in healthy rural villagers. After adjusting for age, gender, and history of epilepsy, hippocampal atrophy/sclerosis was more frequent in patients with calcified NCC than in those with viable cysts (RR, 3.60; 95% CI, 1.18- 0.99; P = 0.025) and healthy rural villagers (RR, 3.43; 95% CI, 1.94-6.06; P < 0.001), suggesting that hippocampal damage develops late in the course of this parasitic disease.

Case Report: Three Cases of Neurocysticercosis in Central Africa.

Neurocysticercosis (NCC) is an infection prevalent in developing countries; however, it is neglected in the Democratic Republic of the Congo (DRC) and in sub-Saharan Africa. Here, we present three different cases seen in a consulting room in Lubumbashi. These cases are evidence that NCC is more common than it was previously thought in sub-Saharan Africa. Neurocysticercosis is a pathology-neglected and ignored infection, not only by the population but also by health professionals and health authorities in the DRC, and because of that, it is important to increase the research about NCC in the DRC to assess the prevalence and risk factors for NCC to assess the severity of the phenomenon and to help designing appropriate prevention and control measures.

Physical fitness and nutritional status in female adolescents with anorexia nervosa / Aptidão física e estado nutricional em adolescentes do sexo feminino com anorexia nervosa

ABSTRACT Objective This study aimed to determine whether physical fitness is related to nutritional status in a sample of female adolescents with anorexia nervosa, to contrast the nourished and undernourished patients, and to compare the physical fitness in these patients with normative data of healthy subjects stratified by age and gender. Methods Nutritional status was determined using the body mass index Z-score, fat mass, fat-free mass (bioelectrical impedance analysis), and the Controlling Nutritional Status score in 15 anorexic adolescents with 14.3±1.6 years. Physical fitness was assessed using the ALPHA-Fitness Battery (handgrip strength, standing broad jump, 4x10m shuttle run, and 20m shuttle run tests). Results Handgrip strength was significantly associated with all variables of nutritional status, except with the three blood components of the Controlling Nutritional Status score. The undernourished anorexic patients showed significantly worse physical fitness than the nourished anorexic patients in all tests, except in the standing broad jump and the 4x10m shuttle run tests. The physical fitness tests of the female anorexic adolescents showed scores significantly worse than those of the normative European female adolescent population. Conclusion The observation of female adolescents with anorexia nervosa showed associations between higher physical fitness levels and better nutritional statuses. Handgrip strength and 20m shuttle run tests may be options of additional indicators of undernutrition in anorexic female adolescents. The undernourished anorexic patients showed worse physical fitness than the nourished ones. According to normative data for healthy sex- and agematched adolescents, physical fitness is severely impaired in anorexic female adolescents.

RESUMO Objetivo Este estudo teve como objetivo determinar se a aptidão física está relacionada ao estado nutricional em uma amostra de adolescentes do sexo feminino com anorexia nervosa, contrastar pacientes nutridas versus desnutridas e comparar a aptidão física nesses pacientes com dados normativos de indivíduos saudáveis estratificados por idade e gênero. Métodos O estado nutricional foi determinado pelo escore Z do índice de massa corporal, massa gorda e massa livre de gordura (análise de impedância bioelétrica) e pelo escore do Estado Nutricional Controlador em 15 adolescentes anoréxicas com 14,3±1,6 anos. A aptidão física foi avaliada usando a Bateria ALPHA-Fitness (força de preensão manual, salto em distância em pé, corrida com vaivém 4x10m e corrida com vaivém de 20m). Resultados A força de preensão manual foi significativamente associada a todas as variáveis do estado nutricional, exceto aos três componentes sanguíneos do escore do Estado de Controle Nutricional. As pacientes anoréxicas desnutridas mostraram uma aptidão física substancialmente pior do que as pacientes anoréxicas nutridas em todos os testes, exceto nos saltos em pé em posição ampla e nos testes de corrida em 4x10m. Os testes de aptidão física dos adolescentes anoréxicos do sexo feminino apresentaram escores consideravelmente piores do que os da população adolescente europeia normativa. Conclusão Adolescentes do sexo feminino com anorexia nervosa apresentaram associação entre maiores níveis de aptidão física e melhor estado nutricional. Os testes de força de preensão manual e corrida de lançadeira de 20m podem ser alternativas como indicadores adicionais do estado de desnutrição em adolescentes anoréxicas. As pacientes anoréxicas desnutridas demonstraram pior condicionamento físico do que as pacientes anoréxicas nutridas. Segundo dados normativos para adolescentes saudáveis de acordo com o sexo e a idade, a aptidão física é gravemente prejudicada em adolescentes anoréxicas do sexo feminino.

Isocitrate dehydrogenase type 2 (IDH2) is part of a multiprotein complex for placental steroidogenesis.

BACKGROUND: Human syncytiotrophoblast mitochondria require the activity of the isocitrate dehydrogenase type 2 (IDH2) to obtain reduced coenzymes for progesterone (P4) synthesis. Data from the literature indicate that mitochondrial steroidogenic contact sites transform efficiently cholesterol into P4. In this research, we identified the IDH2 as a member of the steroidogenic contact site and analyzed the steroidogenic role of its activity. METHOD: Human syncytiotrophoblast mitochondria were isolated by differential centrifugation, and steroidogenic contact sites were obtained by osmotic shock and sucrose gradient ultracentrifugation. In-gel native activity assay, mass spectroscopy, and western blot were used to identify the association of proteins and their activities. P4 was determined by immunofluorescence. RESULTS: The IDH2 was mainly identified in steroidogenic contact sites, and its activity was associated with a complex of proteins with an apparent molecular mass of ~590 kDa. Mass spectroscopy showed many groups of proteins with several metabolic functions, including steroidogenesis and ATP synthesis. The IDH2 activity was coupled to P4 synthesis since in the presence of Ca2+ or Na2SeO3, inhibitors of the IDH2, the P4 production decreased. CONCLUSIONS: The human syncytiotrophoblast mitochondria build contact sites for steroidogenesis. The IDH2, a non-membrane protein, supplies the NADPH required for the synthesis of P4 in a complex (steroidosome) that associate the proteins required to transform efficiently cholesterol into P4, which is necessary in pregnancy to maintain the relationship between mother and fetus. GENERAL SIGNIFICANCE: The IDH2 is proposed as a check point in the regulation of placental steroidogenesis.

Frequency and associated factors of amnestic mild cognitive impairment at four senior citizen clubs in Lima, Peru / Frequência e fatores associados do comprometimento cognitivo leve amnésico em quatro clubes de idosos em lima, peru

ABSTRACT Amnestic mild cognitive impairment (aMCI) is a subtle alteration in cognitive function that does not affect day-to-day activities and can precede Alzheimer's dementia. An increase in the prevalence of both these conditions is expected given the growing elderly population and recognizing risk factors can help reduce the burden. Objective: the aim of this study was to determine the frequency and associated factors of aMCI in senior citizen clubs (SCC) at four districts with different socioeconomic status in Lima, Peru. Methods: we applied Petersen's criteria to determine the presence of the condition in an interview which included the use of the Memory Alteration Test (M@T) and the Pfeffer Functional Activity Questionnaire (PFAQ). Results: sixty-three out of 352 (17.9%) participants had aMCI. Factors associated with this condition were older age, fewer years of education at marriage whereas being from the SCC La Molina (district with highest socioeconomic status and resources for activities for the elderly) were associated with not having aMCI. There was no difference for sex, body mass index or history of hypertension. Conclusion: this predementia stage is frequent and usually undetected in urban Lima. Tools such as the M@T could help general practitioners detect this condition before its progression to dementia.

RESUMO O comprometimento cognitivo leve amnésico (aMCI) é uma alteração sutil na função cognitiva que não altera as atividades do dia-a-dia e pode preceder a demência de Alzheimer. Um aumento na prevalência de ambas as condições é esperado devido ao crescimento da população idosa e o reconhecimento de fatores de risco pode ajudar a reduzir a carga de doença. Objetivo: o objetivo deste estudo foi o de determinar a freqüência e fatores associados a MCI em clubes de cidadãos idosos (CCI) em quatro distritos com diferentes condições socioeconômicas em Lima, Peru. Métodos: aplicamos os critérios de Petersen para determinar a presença da condição em uma entrevista que incluiu o uso do Teste de Alteração de Memória (M@T) e do Questionário de Atividades Funcionais de Pfeffer (QAFP). Resultados: sessenta e três dos 352 (17,9%) participantes tinham MCI. Os fatores associados a essa condição foram idade avançada, menor tempo de estudo ao se casar enquanto ser provenientes do CCI La Molina (distrito com maior nível socioeconômico e recursos para atividades para idosos) foram associados a não possuir um MCI. Não houve diferença por sexo, índice de massa corporal e história de hipertensão. Conclusão: este estágio de pré-demência é frequente e geralmente não detectado na cidade de Lima. Ferramentas como o M@T poderiam ajudar os clínicos gerais a detectar essa condição antes da progressão para a demência.