Racial/ethnic disparities in curative-intent treatment for early-stage non-small cell lung cancer patients among heterogeneous Black populations: US-born Black, Afro-Haitian, West Indian Black, and Hispanic Black.

BACKGROUND: Heterogeneous Black populations encounter significant obstacles in accessing cancer care, yet research on lung cancer treatment disparities remains limited. This study investigates whether the disparity in receiving curative-intent treatment (curative-intent surgery and/or stereotactic body radiation therapy [SBRT]) for early-stage non-small cell lung cancer (NSCLC) between non-Hispanic Whites (NHWs) and total Blacks extends to diverse Black populations, including US-born, Afro-Haitian, West Indian Black, and Hispanic Black individuals. METHODS: This cross-sectional study included all Florida cancer registry early-stage NSCLC cases 2005-2017, linked to individual-level discharge data containing comorbidity and specific treatment details (surgery and/or SBRT). Multivariable logistic regression assessed the association between race/ethnicity and the receipt of curative-intent treatment, while accounting for sociodemographic factors (poverty, age, insurance, and smoking status) and clinical variables. RESULTS: Among 55,655 early-stage NSCLC patients, 71.1% received curative-intent treatment: 72.1% NHW and 59.7% Black (non-Hispanic and Hispanic) individuals. Black patients had 35% lower odds (ORadj, 0.65; 95% CI, 0.59-0.70) of receiving curative-intent treatment compared to NHW patients. ORs varied from 0.57 (95% CI, 0.59-0.70) for Hispanic Black to 0.76 (95% CI, 0.56-1.02) for West Indian Black. Remarkably, Black-White disparities persisted despite the availability of curative treatment options (SBRT) for both high Charlson Comorbidity Index (CCI) observed among US-born Blacks and surgery for low CCI patients among all other Black subgroups. CONCLUSIONS: Pronounced disparities in accessing curative-intent treatments for early-stage NSCLC were evident across all Black subgroups, regardless of treatment availability and comorbidity profile. These findings underscore the need to address Black heterogeneity and prompt further research to rectify treatment disparities in early-stage NSCLC.

Diabetes subgroups and sociodemographic inequalities in Mexico: a cross-sectional analysis of nationally representative surveys from 2016 to 2022.

Background: Differences in the prevalence of four diabetes subgroups have been reported in Mexico compared to other populations, but factors that may contribute to these differences are poorly understood. Here, we estimate the prevalence of diabetes subgroups in Mexico and evaluate their correlates with indicators of social disadvantage using data from national representative surveys. Methods: We analyzed serial, cross-sectional Mexican National Health and Nutrition Surveys spanning 2016, 2018, 2020, 2021, and 2022, including 23,354 adults (>20 years). Diabetes subgroups (obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and age-related [MARD]) were classified using self-normalizing neural networks based on a previously validated algorithm. We used the density-independent social lag index (DISLI) as a proxy of state-level social disadvantage. Findings: We identified 4204 adults (median age: 57, IQR: 47-66, women: 64%) living with diabetes, yielding a pooled prevalence of 16.04% [95% CI: 14.92-17.17]. When stratified by diabetes subgroup, prevalence was 6.62% (5.69-7.55) for SIDD, 5.25% (4.52-5.97) for MOD, 2.39% (1.95-2.83) for MARD, and 1.27% (1.00-1.54) for SIRD. SIDD and MOD clustered in Southern Mexico, whereas MARD and SIRD clustered in Northern Mexico and Mexico City. Each standard deviation increase in DISLI was associated with higher odds of SIDD (OR: 1.12, 95% CI: 1.06-1.12) and lower odds of MOD (OR: 0.93, 0.88-0.99). Speaking an indigenous language was associated with higher odds of SIDD (OR: 1.35, 1.16-1.57) and lower odds of MARD (OR 0.58, 0.45-0.74). Interpretation: Diabetes prevalence in Mexico is rising in the context of regional and sociodemographic inequalities across distinct diabetes subgroups. SIDD is a subgroup of concern that may be associated with inadequate diabetes management, mainly in marginalized states. Funding: This research was supported by Instituto Nacional de Geriatría in Mexico.

Clinical Prognostic Implications of Wnt Hub Genes Expression in Medulloblastoma.

Medulloblastoma is the most common type of pediatric malignant primary brain tumor, and about one-third of patients die due to disease recurrence and most survivors suffer from long-term side effects. MB is clinically, genetically, and epigenetically heterogeneous and subdivided into at least four molecular subgroups: WNT, SHH, Group 3, and Group 4. We evaluated common differentially expressed genes between a Brazilian RNA-seq GSE181293 dataset and microarray GSE85217 dataset cohort of pediatric MB samples using bioinformatics methodology in order to identify hub genes of the molecular subgroups based on PPI network construction, survival and functional analysis. The main finding was the identification of five hub genes from the WNT subgroup that are tumor suppressors, and whose lower expression is related to a worse prognosis for MB patients. Furthermore, the common genes correlated with the five tumor suppressors participate in important pathways and processes for tumor initiation and progression, as well as development and differentiation, and some of them control cell stemness and pluripotency. These genes have not yet been studied within the context of MB, representing new important elements for investigation in the search for therapeutic targets, prognostic markers or for understanding of MB biology.

Single nCounter assay for prediction of MYCN amplification and molecular classification of medulloblastomas: a multicentric study.

PURPOSE: Medulloblastoma is the most frequent pediatric malignant brain tumor, and is divided into four main subgroups: WNT, SHH, group 3, and group 4. MYCN amplification is an important medulloblastoma prognostic biomarker. We aimed to molecular classify and predict MYCN amplification in a single assay. METHODS: It was included 209 medulloblastomas from 205 patients (Brazil, Argentina, and Portugal), divided into training (n = 50) and validation (n = 159) sets. A nCounter assay was carried out using a custom panel for molecular classification, with additional genes, including MYCN. nSolver 4.0 software and the R environment were used for profiling and MYCN mRNA analysis. MYCN amplification by FISH was performed in 64 cases. RESULTS: The 205 medulloblastomas were classified in SHH (44.9%), WNT (15.6%), group 3 (18.1%) and group 4 (21.4%). In the training set, MYCN amplification was detected in three SHH medulloblastomas by FISH, which showed significantly higher MYCN mRNA counts than non-FISH amplified cases, and a cutoff for MYCN amplification was established ([Formula: see text] + 4σ = 11,124.3). Applying this threshold value in the validation set, we identified MYCN mRNA counts above the cutoff in three cases, which were FISH validated. CONCLUSION: We successfully stratified medulloblastoma molecular subgroups and predicted MYCN amplification using a single nCounter assay without the requirement of additional biological tissue, costs, or bench time.

Prevalence Trends of Diabetes Subgroups in the United States: A Data-driven Analysis Spanning Three Decades From NHANES (1988-2018).

CONTEXT: Data-driven diabetes subgroups were proposed as an alternative to address diabetes heterogeneity. However, changes in trends for these subgroups have not been reported. OBJECTIVE: Here, we analyzed trends of diabetes subgroups, stratified by sex, race, education level, age categories, and time since diabetes diagnosis in the United States. METHODS: We used data from consecutive NHANES cycles spanning the 1988-2018 period. Diabetes subgroups (mild obesity-related [MOD], severe insulin-deficient [SIDD], severe insulin-resistant [SIRD], and mild age-related diabetes [MARD]) were classified using validated self-normalizing neural networks. Severe autoimmune diabetes (SAID) was assessed for NHANES-III. Prevalence was estimated using examination sample weights considering bicyclic changes (BCs) to evaluate trends and changes over time. RESULTS: Diabetes prevalence in the United States increased from 7.5% (95% CI 7.1-7.9) in 1988-1989 to 13.9% (95% CI 13.4-14.4) in 2016-2018 (BC 1.09%, 95% CI 0.98-1.31, P < .001). Non-Hispanic Black people had the highest prevalence. Overall, MOD, MARD, and SIDD had an increase during the studied period. Particularly, non-Hispanic Black people had sharp increases in MARD and SIDD, Mexican Americans in SIDD, and non-Hispanic White people in MARD. Males, subjects with secondary/high school, and adults aged 40-64 years had the highest increase in MOD prevalence. Trends in diabetes subgroups sustained after stratifying time since diabetes diagnosis. CONCLUSION: Prevalence of diabetes and its subgroups in the United States has increased from 1988 to 2018. These trends were different across sex, ethnicities, education, and age categories, indicating significant heterogeneity in diabetes within the US obesity burden, population aging, socioeconomic disparities, and lifestyle aspects could be implicated in the increasing trends of diabetes in the United States.

A coordinated approach for the assessment of molecular subgroups in pediatric ependymomas using low-cost methods.

Although ependymoma (EPN) molecular subgroups have been well established by integrated high-throughput platforms, low- and middle-income countries still need low-cost techniques to promptly classify these molecular subtypes. Here, we applied low-cost methods to classify EPNs from a Brazilian cohort with 60 pediatric EPN patients. Fusion transcripts (C11orf95-RELA, YAP1-MAMLD1, and YAP1-FAM118B) were investigated in supratentorial EPN (ST-EPNs) samples through RT-PCR/Sanger sequencing and immunohistochemistry (IHC) for p65/L1CAM. qRT-PCR and IHC were used to evaluate expression profiling of CXorf67, LAMA2, NELL2, and H3K27me3 in posterior fossa EPN (PF-EPNs) samples. In silico analysis was performed using public microarray data to validate the molecular assignment PF-EPNs with LAMA2/NELL2 markers. RELA cases and YAP1-MAMLD1 fusions were identified in nine and four ST-EPNs, respectively. An additional RELA case was identified by IHC. Of note, LAMA2 and NELL2 gene expression and immunoprofiling were less accurate for classifying PF-EPNs, which were confirmed by in silico analysis. Yet, H3K27me3 staining was sufficient to classify PF-EPN subgroups. Our results emphasize the feasibility of a simplified strategy to molecularly classify EPNs in the vast majority of cases (49/60; 81.7%). A coordinated combination of simple methods can be effective to screen pediatric EPN with the available laboratory resources at most low-/mid-income countries, giving support for clinical practice in pediatric EPN. KEY MESSAGES: Low- and middle-income countries need effective low-cost approaches to promptly distinguish between EPN molecular subgroups. RT-PCR plus Sanger sequencing is able to recognize the most common types of RELA and YAP1 fusion transcripts in ST-EPNs. Genetic and protein expressions of LAMA2 and NELL2 are of limited value to accurately stratify PF-EPNs. Immunohistochemical staining for H3K27me3 may be used as a robust method to accurately diagnose PF-EPNs subgroups. A coordinated flow diagram based on these validated low-cost methods is proposed to help clinical-decision making and to reduce costs with NGS assessment outside research protocols.

Diseño y optimización de un tubo policromático de citometría de flujo para inmunofenotipo linfocitario periférico / Design and optimization of a polychromatic tube of flow cytometry for peripheral lymphocyte immunophenotype

Introducción: La citometría de flujo permite la cuantificación de las subpoblaciones de linfocitos con una elevada sensibilidad, especificidad y objetividad. Estas ventajas solo se logran con un proceso laborioso de diseño individualizado y controlado para cada experimento. Objetivo: Diseñar un protocolo de un solo tubo policromático de citometría flujo para inmunofenotipo linfocitario periférico. Métodos: Se realizó un estudio experimental in vitro con muestras de sangre periférica obtenidas de tres voluntarios sanos, en el Centro Nacional de Genética Médica, en marzo de 2019. El tubo se compuso de seis marcadores de linaje para identificar linfocitos B, T, natural killer y natural killer T. Se desarrolló un protocolo de lisis de hematíes sin lavado. Se emplearon anticuerpos monoclonales conjugados con fluorocromos. El punto óptimo de concentración correspondió al mayor índice de tinción y conservación de los porcentajes de positividad de cada población. Se realizó la construcción progresiva del tubo y se propuso una estrategia lógica de secuencia de ventanas para el análisis de datos. Resultados: Los marcadores seleccionados permitieron realizar correctamente el inmunofenotipo linfocitario periférico. En los cinco puntos de titulación se observaron buenas discriminaciones entre las señales positivas y negativas, excepto para el anti-CD56 que presentó una tendencia decreciente del índice de tinción. El volumen total de conjugados requeridos para la determinación de los 6 antígenos fue de 3,75 μL por tubo. Conclusiones: Se obtuvo un tubo policromático que permite el inmunofenotipo periférico de forma rápida y precisa por seis antígenos linfocitarios simultáneamente, con el empleo de pequeños volúmenes de conjugado y sangre(AU)

Introduction: Flow cytometry allows quantification of lymphocyte subpopulations with high sensitivity, specificity and objectivity. These advantages are only achieved through the hardworking process of individualized and controlled design for each experiment. Objective: To design a flow cytometry protocol of a single polychromatic tube for peripheral lymphocyte immunophenotype. Methods: An experimental in vitro study was carried out, in March 2019, with peripheral blood samples obtained from three healthy volunteers, at the National Center for Medical Genetics. The tube was made up of six lineage markers for identifying natural B and T lymphocytes, natural killers and natural killer T cells. A protocol was developed for red blood cell lysis without washing. Fluorochrome-conjugated monoclonal antibodies were used. The optimal point of concentration corresponded to the highest staining index and preservation of the positivity percentages of each population. Progressive tube construction was performed and a logical window sequence strategy was proposed for data analysis. Results: The chosen markers allowed to carry out correct peripheral lymphocyte immunophenotype. Good discriminations between positive and negative signals were observed at the five titration points, except for anti-CD56, which presented a decreasing trend in the staining index. The total volume of conjugates required for determination of the six antigens was 3.75 μL per tube. Conclusions: A polychromatic tube was obtained that allows to carry out peripheral immunophenotype quickly and precisely by six lymphocyte antigens simultaneously, with the use of small volumes of conjugate and blood(AU)

Caracterización de los inmunofenotipos linfocitarios de sangre periférica en pacientes con cáncer / Characterization of peripheral blood lymphocytes immunophenotype in cancer patients

Introducción: La determinación de los inmunofenotipos linfocitarios en sangre periférica forma parte de la evaluación del estado general del sistema inmunitario. Estos exámenes ofrecen informaciones sobre la distribución, concentración y funcionabilidad de las células inmunitarias, lo cual contribuye a establecer pronósticos en el cáncer y predicciones a las respuestas terapéuticas. Objetivo: Evaluar la distribución de las concentraciones linfocitarias circulantes en sangre periférica de pacientes con cáncer. Métodos: Se realizó un estudio analítico en 154 pacientes con cáncer, atendidos en el Instituto de Oncología y Radiobiología de La Habana, durante los años 2017 a 2019. Se empleó la citometría de flujo multiparamétrica para identificar los inmunofenotipos linfocitarios. Este procedimiento se realizó antes de comenzar cualquier tratamiento inmunoterapéutico. Resultados: Los pacientes con cáncer mostraron mayor heterogeneidad en la distribución de las poblaciones linfocitarias respecto a los controles. En los pacientes la mediana de los linfocitos totales y de las subpoblaciones linfocitarias CD3+, CD4+, CD8+ y CD19+ fueron significativamente menores. Los linfocitos T dobles positivos (CD4/CD8) se encontraron elevados significativamente. No se hallaron diferencias entre sexos. La edad se asoció negativamente con las concentraciones de las poblaciones T en tumores sólidos, y con T y B en los linfomas. En el cáncer de próstata se obtuvieron los valores más bajos de poblaciones linfocitarias. Conclusiones: Los pacientes con cáncer tienen menor concentración de linfocitos en sangre periférica que los controles sanos. Las células más afectadas fueron las subpoblaciones T y los linfocitos B. La edad se asoció negativamente con las concentraciones sanguíneas de linfocitos, lo cual pudiera estar en relación con la inmunosenescencia(AU)

Introduction: Determination of lymphocytic immunophenotypes in peripheral blood is part of the evaluation of the general state of the immune system. These tests provide information about the distribution, concentration, and functionality of immune cells, which helps establish prognoses in cancer and predictions of therapeutic responses. Objective: To evaluate the distribution of circulating lymphocyte concentrations in peripheral blood of cancer patients. Methods: An analytical study was carried out with 154 cancer patients treated at the Institute of Oncology and Radiobiology in Havana, from 2017 to 2019. Multiparametric flow cytometry was used to identify lymphocyte immunophenotypes. This procedure was performed before beginning any immunotherapeutic treatment. Results: Cancer patients showed greater heterogeneity in the distribution of lymphocyte populations compared to control patients. The median for total lymphocytes and the lymphocyte subpopulations of CD3+, CD4+, CD8+ and CD19+ were significantly lower in patients. CD4+ CD8+ double-positive T lymphocytes were found to be significantly elevated. No sex differences were found. Age was negatively associated with the concentrations of T-cells populations in solid tumors, and with T- and B-cells populations in lymphomas. In prostate cancer, the lowest values ​​of lymphocyte populations were obtained. Conclusions: Cancer patients have a lower concentration of lymphocytes in peripheral blood than healthy patients in the control group. The most affected ones were the T-cells subpopulations and B lymphocytes. Age was negatively associated with blood levels of lymphocytes, which could be related to immunosenescence(AU)

MTHFR rs1801133 polymorphism is associated with increased risk of B-cell precursor lymphoblastic leukaemia with recurrent genetic aberrations of fetal origin.

BACKGROUND: Childhood acute lymphoblastic leukaemia (ALL) is a heterogeneous disease associated with multiple risk factors including genetic susceptibility. Polymorphisms in folate genes have been associated with a protective effect against ALL, although some studies contradict these findings. We aimed to test whether there is an association between the MTHFR rs1801133 variant and the occurrence of B-cell precursor ALL (BCP-ALL) taking in account molecularly distinct subtypes of fetal origin. METHODS: We performed a case-control genotyping study with 2067 samples, 1309 ALL and 758 controls, from children aged ≤ 15 years for MTHFR rs1801133 polymorphism. Risk associations were calculated by odds ratios estimated with unconditional logistic regression, adjusted for frequency-matched ethnic groups. RESULTS: Overall, MTHFR rs1801133 does not impact ALL risk in children with more than 6 years of age. A significant positive association for MTHFR rs1801133 variant was found for ALL with KMT2A-r in the dominant model (adj. OR, 1.48, 95 % CI, 1.01-2.17), while ETV6-RUNX1 and Hyperdiploid subgroups have shown a borderline effect (adj. OR, 1.33, 95 % CI, 0.99-1.78). CONCLUSIONS: The polymorphism MTHFR rs1801133 increased the risk of infant ALL in Brazilian population.

Lack of KBTBD4 Mutations in Molecularly Classified Brazilian Medulloblastomas.

Medulloblastoma is the most frequent malignant brain tumor in children, representing 20% of all childhood brain tumors. Currently, medulloblastomas are molecularly classified in 4 subgroups that are associated with distinctive clinicopathological features. KBTBD4 mutations were recently described in a subset of MBGRP3 and MBGRP4 medulloblastomas subgroups. However, no other studies reported KBTBD4 mutations in medulloblastomas. Thus, our aim was to investigate KBTBD4 mutations in a Brazilian series of medulloblastoma. We evaluated 128 medulloblastoma patients molecularly classified from 4 Brazilian reference centers. DNA from formalin-fixed, paraffin-embedded samples was screened for KBTBD4 hotspot mutations by Sanger sequencing. Most of the patients were male, average age was 16.5 years old and average overall survival was 55.9 months. The predominant histological subtype was the classic subtype, followed by nodular/desmoplastic, and the predominant medulloblastoma molecular subtype was the MBSHH subgroup (46%), followed by MBGRP3 and MBGRP4 (19%/each), and MBWNT (16%). Among the 128 samples, 111 were successfully sequenced. No KBTBD4 mutations were identified in 111 samples. Our findings suggest that KBTBD4 mutations are uncommon in Brazilian MBGRP3 and MBGRP4 medulloblastomas subgroups. Further studies in a larger series of MBGRP3 and MBGRP4 medulloblastomas are warranted to better assess role of KBTBD4 mutations.

A simplified approach using Taqman low-density array for medulloblastoma subgrouping.

Next-generation sequencing platforms are routinely used for molecular assignment due to their high impact for risk stratification and prognosis in medulloblastomas. Yet, low and middle-income countries still lack an accurate cost-effective platform to perform this allocation. TaqMan Low Density array (TLDA) assay was performed using a set of 20 genes in 92 medulloblastoma samples. The same methodology was assessed in silico using microarray data for 763 medulloblastoma samples from the GSE85217 study, which performed MB classification by a robust integrative method (Transcriptional, Methylation and cytogenetic profile). Furthermore, we validated in 11 MBs samples our proposed method by Methylation Array 450 K to assess methylation profile along with 390 MB samples (GSE109381) and copy number variations. TLDA with only 20 genes accurately assigned MB samples into WNT, SHH, Group 3 and Group 4 using Pearson distance with the average-linkage algorithm and showed concordance with molecular assignment provided by Methylation Array 450 k. Similarly, we tested this simplified set of gene signatures in 763 MB samples and we were able to recapitulate molecular assignment with an accuracy of 99.1% (SHH), 94.29% (WNT), 92.36% (Group 3) and 95.40% (Group 4), against 97.31, 97.14, 88.89 and 97.24% (respectively) with the Ward.D2 algorithm. t-SNE analysis revealed a high level of concordance (k = 4) with minor overlapping features between Group 3 and Group 4. Finally, we condensed the number of genes to 6 without significantly losing accuracy in classifying samples into SHH, WNT and non-SHH/non-WNT subgroups. Additionally, we found a relatively high frequency of WNT subgroup in our cohort, which requires further epidemiological studies. TLDA is a rapid, simple and cost-effective assay for classifying MB in low/middle income countries. A simplified method using six genes and restricting the final stratification into SHH, WNT and non-SHH/non-WNT appears to be a very interesting approach for rapid clinical decision-making.

First detection of porcine circovirus type 3 in Colombia and the complete genome sequence demonstrates the circulation of PCV3a1 and PCV3a2.

Porcine circovirus 3 (PCV3) was recently discovered and is a new species of the genus circovirus. Clinically, it is associated with absence of symptoms or with different clinical syndromes. It has been reported in different countries of America, Europe and Asia. Last year, in Colombia, some farms have reported symptoms similar to those caused by PCV2. Samples were taken from two farms located in the centre of the country, and the presence of PCV3 was determined by PCR in two samples, one from a pool of sera and another from mesenteric lymph node. The strains were fully sequenced (GenBank accession numbers MH327784 and MH327785) and classified into subgroups a1 and a2. According to this classification and its analysis, strain a2 is located within the group called "Linker" that may be evolving towards group "b". In addition to the above, the two Colombian strains were compared with 104 strains reported in the GenBank database. The phylogenetic tree obtained grouped according to the classification of subgroups a1, a2, b1 and b2. It was found that subgroups a1 and a2 were well grouped when comparing whole genomes, but the same was not observed with the strains of group "b". In the latter, no subgroups were evidenced when comparing complete genomes. It is suggested that a new classification of PCV3 subgroups should be proposed, based on whole genome sequences. This is the first report of PCV3 in Colombia and its complete genome sequence.

Seasonal and sex differences in the fission-fusion dynamics of spider monkeys (Ateles geoffroyi yucatanensis) in Belize.

Spider monkeys (Ateles sp.) are characterized by high fission-fusion dynamics, meaning their social grouping pattern is fluid and consists of subgroups that vary in size, composition, and spatial cohesion over time. In this study, we quantify the fission-fusion dynamics of a group of spider monkeys at Runaway Creek Nature Reserve in Belize by measuring subgroup size, spatial cohesion, and stability using data spanning 5 years. We then test whether variation in these three subgroup measures differ according to season, subgroup sex composition, and the reproductive status of female subgroup members. Our results show that subgroups were larger in size and less stable in membership during the wet season compared to the dry season. All-female subgroups were less spatially cohesive but more stable in membership than all-male subgroups. Finally, we report that subgroups with one or more non-lactating females (i.e., without nursing young) were smaller on average than subgroups containing lactating females with nursing young. These data contribute to a growing body of research documenting the ecological and social dimensions along which grouping patterns might vary.

Reproducibility of the NanoString 22-gene molecular subgroup assay for improved prognostic prediction of medulloblastoma.

Medulloblastoma is the most frequent malignant brain tumor in children. Four medulloblastoma molecular subgroups, MBSHH , MBWNT , MBGRP3 and MBGRP4 , have been identified by integrated high-throughput platforms. Recently, a 22-gene panel NanoString-based assay was developed for medulloblastoma molecular subgrouping, but the robustness of this assay has not been widely evaluated. Mutations in the gene for human telomerase reverse transcriptase (hTERT) have been found in medulloblastomas and are associated with distinct molecular subtypes. This study aimed to implement the 22-gene panel in a Brazilian context, and to associate the molecular profile with patients' clinical-pathological features. Formalin-fixed, paraffin-embedded (FFPE) medulloblastoma samples (n = 104) from three Brazilian centers were evaluated. Expression profiling of the 22-gene panel was performed by NanoString and a Canadian series (n = 240) was applied for training phase. hTERT mutations were analyzed by PCR followed by direct Sanger sequencing and the molecular profile was associated with patients' clinicopathological features. Overall, 65% of the patients were male, average age at diagnosis was 18 years and 7% of the patients presented metastasis at diagnosis. The molecular classification was attained in 100% of the cases, with the following frequencies: MBSHH (n = 51), MBWNT (n = 19), MBGRP4 (n = 19) and MBGRP3 (n = 15). The MBSHH and MBGRP3 subgroups were associated with older and younger patients, respectively. The MBGRP4 subgroup exhibited the lowest 5-year cancer-specific overall survival (OS), yet in the multivariate analysis, only metastasis at diagnosis and surgical resection were associated with OS. hTERT mutations were detected in 29% of the cases and were associated with older patients, increased hTERT expression and MBSHH subgroup. The 22-gene panel provides a reproducible assay for molecular subgrouping of medulloblastoma FFPE samples in a routine setting and is well-suited for future clinical trials.

Structure, function and evolution of the hemerythrin-like domain superfamily.

Hemerythrin-like proteins have generally been studied for their ability to reversibly bind oxygen through their binuclear nonheme iron centers. However, in recent years, it has become increasingly evident that some members of the hemerythrin-like superfamily also participate in many other biological processes. For instance, the binuclear nonheme iron site of YtfE, a hemerythrin-like protein involved in the repair of iron centers in Escherichia coli, catalyzes the reduction of nitric oxide to nitrous oxide, and the human F-box/LRR-repeat protein 5, which contains a hemerythrin-like domain, is involved in intracellular iron homeostasis. Furthermore, structural data on hemerythrin-like domains from two proteins of unknown function, PF0695 from Pyrococcus furiosus and NMB1532 from Neisseria meningitidis, show that the cation-binding sites, typical of hemerythrin, can be absent or be occupied by metal ions other than iron. To systematically investigate this functional and structural diversity of the hemerythrin-like superfamily, we have collected hemerythrin-like sequences from a database comprising fully sequenced proteomes and generated a cluster map based on their all-against-all pairwise sequence similarity. Our results show that the hemerythrin-like superfamily comprises a large number of protein families which can be classified into three broad groups on the basis of their cation-coordinating residues: (a) signal-transduction and oxygen-carrier hemerythrins (H-HxxxE-HxxxH-HxxxxD); (b) hemerythrin-like (H-HxxxE-H-HxxxE); and, (c) metazoan F-box proteins (H-HExxE-H-HxxxE). Interestingly, all but two hemerythrin-like families exhibit internal sequence and structural symmetry, suggesting that a duplication event may have led to the origin of the hemerythrin domain.

Effectiveness of the addition of therapeutic alliance with minimal intervention in the treatment of patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors: a study protocol for a randomized controlled trial (TalkBack trial).

BACKGROUND: The stratified model of care has been an effective approach for the treatment of low back pain. However, the treatment of patients with low risk of psychosocial-factor involvement is unclear. The addition of the therapeutic alliance to a minimal intervention may be an option for the treatment of low back pain. This paper reports on the rationale, design and protocol for a randomized controlled trial with blind assessor to assess the effectiveness of the addition of therapeutic alliance with minimal intervention on pain and disability in patients with chronic, nonspecific low back pain. METHODS: Two hundred and twenty-two patients with chronic, nonspecific low back pain and low risk of involvement of psychosocial factors will be assessed and randomly allocated into three groups (n = 74 patients per group). The Positive Therapeutic Alliance group will receive counseling and guidance with an emphasis on therapeutic alliance and empathy. The Usual Treatment group will receive the same information and counseling with limited interaction with the therapist. The Control group will not receive any intervention. The treatment will be composed by two intervention sessions with a 1-week interval. A blinded assessor will collect the following outcomes at baseline, 1 month, 6 months and 12 months after randomization: pain intensity (Pain Numerical Rating Scale), specific disability (Patient-specific Functional Scale), general disability (Oswestry Disability Index), global perceived effect (Global Perceived Effect Scale), empathy (Consultation and Relational Empathy Measure), credibility and expectations related to treatment. The analysis will be performed using linear mixed models. DISCUSSION: This will be the first study to understand the effect of combining enhanced therapeutic alliance to a treatment based on counseling, information and advice (minimal intervention). The addition of the therapeutic alliance to minimal intervention may improve the treatment of chronic, nonspecific low back pain. TRIAL REGISTRATION: ClinicalTrials.gov, NCT 02497625. Registered on 10 July 2015.

Hypertension Prevalence in New York City Adults: Unmasking Undetected Racial/Ethnic Variation, NYC HANES 2004.

OBJECTIVE: Using 2004 New York City Health and Nutrition Examination Survey (NYC HANES) data, we sought to examine variation in hypertension (HTN) prevalence across eight Asian and Hispanic subgroups. DESIGN: Cross-sectional. SETTING: New York City, 2004. MAIN OUTCOME MEASURES: Logistic regression was performed to identify differences in HTN prevalence between ethnic subgroups controlling for age, sex, education and BMI. RESULTS: Overall HTN prevalence among NYC adults was 25.5% (95% CI: 23.4-27.8), with 21.1% (95% CI: 18.2-24.3) among Whites, 32.8% (95% CI: 28.7-37.2) Black, 26.4% (95% CI: 22.3-31.0) Hispanics, and 24.7% (95% CI: 19.9-30.3) Asians. Among Hispanic subgroups, Dominicans had the highest HTN prevalence (32.2%), followed by Puerto Ricans (27.7%), while Mexicans had the lowest prevalence (8.1%). Among Asian subgroups, HTN prevalence was slightly higher among South Asians (29.9%) than among Chinese (21.3%). Adjusting for age, Dominican adults were nearly twice as likely to have HTN as non-Hispanic (NH) Whites (OR=1.96, 95% CI: 1.24-3.12), but this was attenuated after adjusting for sex and education (OR=1.27, 95% CI: .76 - 2.12). When comparing South Asians with NH Whites, results were also non-significant after adjustment (OR=2.00, 95% CI: .90-4.43). CONCLUSIONS: When analyzing racial/ethnic subgroups, NH Black and Hispanic adults from Dominican Republic had the highest HTN prevalence followed by South Asian and Puerto Rican adults. Mexican adults had the lowest prevalence of all groups. These findings highlight that ethnic subgroup differences go undetected when stratified by broader racial/ethnic categories. To our knowledge, this is the first population-based study using objective measures to highlight these differences.

Acculturation dimensions and 12-month mood and anxiety disorders across US Latino subgroups in the National Epidemiologic Survey of Alcohol and Related Conditions.

BACKGROUND: Individual-level measures of acculturation (e.g. age of immigration) have a complex relationship with psychiatric disorders. Fine-grained analyses that tap various acculturation dimensions and population subgroups are needed to generate hypotheses regarding the mechanisms of action for the association between acculturation and mental health. METHOD: Study participants were US Latinos (N = 6359) from Wave 2 of the 2004-2005 National Epidemiologic Survey of Alcohol and Related Conditions (N = 34 653). We used linear χ2 tests and logistic regression models to analyze the association between five acculturation dimensions and presence of 12-month DSM-IV mood/anxiety disorders across Latino subgroups (Mexican, Puerto Rican, Cuban, 'Other Latinos'). RESULTS: Acculturation dimensions associated linearly with past-year presence of mood/anxiety disorders among Mexicans were: (1) younger age of immigration (linear χ2 1 = 11.04, p < 0.001), (2) longer time in the United States (linear χ2 1 = 10.52, p < 0.01), (3) greater English-language orientation (linear χ2 1 = 14.57, p < 0.001), (4) lower Latino composition of social network (linear χ2 1 = 15.03, p < 0.001), and (5) lower Latino ethnic identification (linear χ2 1 = 7.29, p < 0.01). However, the associations were less consistent among Cubans and Other Latinos, and no associations with acculturation were found among Puerto Ricans. CONCLUSIONS: The relationship between different acculturation dimensions and 12-month mood/anxiety disorder varies across ethnic subgroups characterized by cultural and historical differences. The association between acculturation measures and disorder may depend on the extent to which they index protective or pathogenic adaptation pathways (e.g. loss of family support) across population subgroups preceding and/or following immigration. Future research should incorporate direct measures of maladaptive pathways and their relationship to various acculturation dimensions.

Hispanic Subgroups, Acculturation, and Substance Abuse Treatment Outcomes.

This study explored Hispanic subgroup differences in substance use treatment outcomes, and the relationship of acculturation characteristics to these outcomes. Data were from a multisite randomized clinical trial of motivational enhancement therapy versus treatment as usual in a sample of Spanish-speaking substance abusers. Participants were Cuban American (n=34), Mexican American (n=209), Puerto Rican (n=78), and other Hispanic American (n=54). Results suggested that Cuban Americans and individuals with more connection to Hispanic culture had lower treatment retention. Hispanics born in the U.S and those who spoke English at home had a lower percentage of days abstinent during weeks 5-16, although Puerto Ricans born in the U.S. and Cuban Americans living more years in the U.S. had a higher percentage of days abstinent in weeks 1-4 and 5-16, respectively. Results may inform future hypothesis-driven studies in larger Hispanic treatment seeking samples of the relationship between acculturation and treatment outcome.

HIV-Related Mortality Among Adults (≥ 18 years) of Various Hispanic or Latino Subgroups--United States, 2006-2010.

Hispanics or Latinos residing in the USA are disproportionately affected by HIV when compared to whites. Health outcomes for Hispanics or Latinos diagnosed with HIV infection may vary by Hispanic or Latino subgroup. We analyzed national mortality data from the National Center for Health Statistics for the years 2006 to 2010 to examine differences in HIV-related mortality among Hispanics or Latinos by sociodemographic factors and by Hispanic or Latino subgroup. After adjusting for age, HIV-related death rates per 100,000 population were highest among Hispanics or Latinos who were male (45.6, 95 % confidence interval [CI], 44.4 to 46.9) compared to female (12.0, 95 % CI 11.4 to 12.6), or resided in the Northeast (75.1, 95 % CI 72.2 to 77.9) compared to other US regions at the time of death. The age-adjusted HIV-related death rate was highest among Puerto Ricans (100.9, 95 % CI 97.0 to 104.8) and lowest among Mexicans (16.9, 95 % CI 16.2 to 17.6). Among all deaths, the proportion of HIV-related deaths was more than four times as high among Puerto Ricans (adjusted prevalence ratio = 4.3, 95 % CI 4.1 to 4.5) compared to Mexicans. To ensure better health outcomes for Hispanics or Latinos living with HIV in the USA, medical care and treatment programs should be adapted to address the needs of various Hispanic or Latino subgroups.