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Background: Historically, the Andean people have experienced uncertainty in terms of the availability of food resources because of climatic and ecological variations that are typical of mountainous environments. Risk management strategies, including the diversified and complementary use and management of species and ecosystems at different elevations, have faced such uncertainty. The current effects of climate change on food security motivate studies on subsistence adaptative strategies. TEK offers extraordinary experience and local biocultural memory to meet present and future needs. From an ethnoecological perspective, we aim to identify the variety of local foods in Andean communities, their cultural and nutritional value for local people, their use frequencies, and their forms to obtain them from different environments, productive systems, and interchanges. We expected to identify traditional Andean diversified subsistence patterns despite the pressure of modern food and interchange systems., Methods: This study was conducted in two communities in the highlands of the Department of Huánuco, Peru. We conducted 24 semistructured interviews with households sampled through the snowball method. We asked about their daily life food, plant and animal components of diet, frequencies and seasons in which they are consumed, and ways to obtain them. We complemented the information through ethnobotanical collection of wild, weedy, and ruderal edible plants and records on domestic and wild animals included in the diet., Results: We recorded 37 crop species, 13 domestic animals, 151 wild, weedy, and ruderal food plant species, the 3 most commonly consumed wild animals, and 52 processed products obtained from local stores and markets. The main crops are potato and maize, while the main domestic animals included in the diet are cattle, pigs, and sheep. Rice, pasta, and bread are the main raw and processed foods included in the diet. Crops represent nearly half of the food consumed and purchased (in kg/year), and tubers and cereals provide most of the kilocalories, carbohydrates and proteins. Wild, weedy, and ruderal plants are consumed in relatively low amounts and at relatively low frequencies per species, but overall, they constitute a significant proportion of the kg of annually consumed food (14.4% in Cani and 9.6% in Monte Azul). Knowledge and use of these resources play a key role in local cuisine and nutrition., Conclusion: The current food patterns studied are based on diverse diets, including multiple feedstuffs, sources, and practices to obtain them, which reflects the traditional Andean subsistence pattern. The increasing adoption of processed food has influenced the declining consumption of local food, mainly among young people. Communication and policies to promote local food, emphasizing the role of wild plants and their adequate consumption, and provide information on their nutritional value are recommended to support efforts toward food sovereignty and conservation of Andean biocultural diversity., (© 2024. The Author(s).)

Background: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder caused by germline mutations in the APC gene. Patients with FAP have multiple extraintestinal manifestations that follow a genotype-phenotype pattern; however, few data exist characterizing their cognitive abilities. Given the role of the APC protein in development of the central nervous system, we hypothesized that patients with FAP would show differences in cognitive functioning compared to controls., Methods: Matched case-control study designed to evaluate cognitive function using the Test of Nonverbal Intelligence-4, the Bateria III Woodcock-Munoz, and the Behavior Rating Inventory of Executive Functions-Adult. Twenty-six individuals with FAP (mean age = 34.2 ± 15.0 years) and 25 age-gender and educational level matched controls (mean age = 32.7 ± 13.8 years) were evaluated., Results: FAP-cases had significantly lower IQ ( p  = 0.005). Across all tasks of the Batería III Woodcock-Muñoz, FAP-cases performed significantly lower than controls, with all of the summary scores falling in the bottom quartile compared to controls ( p  < 0.0001). Patients with FAP scored within the deficient range for Long-Term Retrieval and Cognitive Fluency., Conclusion: APC protein has an important role in neurocognitive function. The pervasive nature of the observed cognitive dysfunction suggests that loss or dysfunction of the APC protein impacts processes in cortical and subcortical brain regions. Additional studies examining larger ethnically diverse cohorts with FAP are warranted., Competing Interests: Competing interestsMCC is advisor of EXACT Sciences and BeiGene Pharmaceuticals. Content related to her advisory roles is not related to the topic of the manuscript., (© The Author(s). 2020.)

Background: The microbiome greatly affects health and wellbeing. Evolutionarily, it is doubtful that a host would rely on chance alone to pass on microbial colonization to its offspring. However, the literature currently offers only limited evidence regarding two alternative hypotheses: active microbial shaping by host genetic factors or transmission of a microbial maternal legacy. Results: To further dissect the influence of host genetics and maternal inheritance, we collected two-cell stage embryos from two representative wild types, C57BL6/J and BALB/c, and transferred a mixture of both genotype embryos into hybrid recipient mice to be inoculated by an identical microbiome at birth. Conclusions: Observing the offspring for six generations unequivocally emphasizes the impact of host genetic factors over maternal legacy in constant environments, akin to murine laboratory experiments. Interestingly, maternal legacy solely controlled the microbiome in the first offspring generation. However, current evidence supporting maternal legacy has not extended beyond this initial generation, resolving the aforementioned debate. BvkFmArGExF4DhB6h6D8wq Video Abstract [ABSTRACT FROM AUTHOR]

Background: To evaluate the midterm results of patients with angina and diffuse coronary artery disease treated with transmyocardial revascularization in combination with autologous stem cell therapy., Methods: Nineteen patients with diffuse coronary artery disease and medically refractory class III/IV angina were evaluated between June 2007 and December 2009 for sole therapy TMR combined with intramyocardial injection of concentrated stem cells. At the time of surgery, autologous bone marrow (120cc) was aspirated from the iliac crest. A cardiac MRI and an isotopic test were performed before and after the procedure. Follow-up was performed by personal interview., Results: There were no perioperative adverse events including no arrhythmias. Mean number of laser channels was 20 and the mean total number of intramyocardially injected cells per milliliter were: total mononuclear cells(83.6 × 10(6)), CD34+ cells(0.6 × 10(6)), and CD133+ cells(0.34 × 10(6)). At 12 months mean follow-up average angina class was significantly improved (3.4 ± 0.5 vs 1.4 ± 0.6; p = 0.004). In addition, monthly cardiovascular medication usage was significantly decreased (348 ± 118 vs. 201 ± 92; p = 0.001). At six months follow up there was a reduction in the number of cardiac hospital readmissions (2.9 ± 2.3 vs. 0.5 ± 0.8; p < 0.001). MRI showed no alterations regarding LV volumes and a 3% improvement regarding ejection fraction., Conclusions: The stem cell isolator efficiently concentrated autologous bone marrow derived stem cells while the TMR/stem cell combination delivery device worked uneventfully. An improvement in clinical status was noticed in the midterm follow-up. Images test showed no morphological alterations in the left ventricle after the procedure.

Introduction: We report a rare case of a ganglion cyst at the elbow causing neurological symptoms by stretching the superficial radial nerve alone. Ganglia associated with radial nerve palsy at the elbow have been reported previously involving the deep branch of the posterior interosseous nerve and the superficial radial nerve, but not the superficial radial nerve alone., Case Presentation: A 45-year-old woman presented with a 4-month history of a painful lump in the anterior aspect of her left elbow associated with altered sensation in the dorsoradial aspect of her left hand. There was no history of trauma or any exacerbating factors. On examination the altered sensation was in the superficial radial nerve distribution and she had a positive Tinel's sign over the site of the swelling which was located over the anterior aspect of the radiocapitellar joint., Conclusion: The unique clinical symptoms and signs of our diagnosis of superficial radial nerve compression were confirmed by magnetic resonance imaging and then operative findings.

Introduction: Thymic epithelial tumors (TETs) are rare neoplasms often associated with immune-related disorders. Patients with Good's syndrome (GS), an adult-acquired TET-related immunodeficiency, are at a high risk of mortality due to infectious diseases. This study aims to examine COVID-19 occurrence and severity in TET patients, with or without GS. Methods: Clinical records of TET patients referred to the Regional Coordinating Center for Rare Tumors of Campania Region were retrospectively collected. During the observation period, elapsing from March 2020 to April 2023, the following data were collected: occurrence of SARS-CoV-2 infection; COVID-19 severity, according to the National Institute of Health (NIH) illness categories; COVID-19 treatment. COVID-19 occurrence and severity were assessed in the overall population and correlated with the presence of GS and/or other immune-related dysregulations. Results: Overall, 47 TET patients were included in the study; 27 of these (57.4%) had GS. All participants had received a full cycle of mRNA vaccine for SARS-CoV2., Thirty-one patients (66.0%) experienced COVID-19, of whom 18 (58.0%) had previously received a diagnosis of GS. No significant association of GS and/or other immune-related dysregulations with SARS-CoV-2 infection occurrence was detected (Fisher's exact test p = 1 and p = 0.3587, respectively). Among patients with GS, 8 (45.0%) reported a COVID-19 severity score of ≥ 3; whereas, only 1 of the 13 patients without GS (7.7%) had a severity score of ≥ 3. The correlation between presence of GS and COVID-19 severity (score 1 or 2 vs. ≥ 3) was statistically significant (p = 0.0448). No statistically significant association between COVID-19 severity and other immune-related syndromes were found (p = 1). Of note, all the hospitalized patients for NIH 4 and 5 COVID-19 had GS. Conclusions: Our data suggest that TET patients, especially those with GS, require a careful multidisciplinary monitoring for SARS-CoV-2 infection, in order to establish tailored treatments and prophylactic protocols. [ABSTRACT FROM AUTHOR]

Synthetic antibodies (Abs) represent a category of artificial proteins capable of closely emulating the functions of natural Abs. Their in vitro production eliminates the need for an immunological response, streamlining the process of Ab discovery, engineering, and development. These artificially engineered Abs offer novel approaches to antigen recognition, paratope site manipulation, and biochemical/biophysical enhancements. As a result, synthetic Abs are fundamentally reshaping conventional methods of Ab production. This mirrors the revolution observed in molecular biology and genomics as a result of deep sequencing, which allows for the swift and cost-effective sequencing of DNA and RNA molecules at scale. Within this framework, deep sequencing has enabled the exploration of whole genomes and transcriptomes, including particular gene segments of interest. Notably, the fusion of synthetic Ab discovery with advanced deep sequencing technologies is redefining the current approaches to Ab design and development. Such combination offers opportunity to exhaustively explore Ab repertoires, fast-tracking the Ab discovery process, and enhancing synthetic Ab engineering. Moreover, advanced computational algorithms have the capacity to effectively mine big data, helping to identify Ab sequence patterns/features hidden within deep sequencing Ab datasets. In this context, these methods can be utilized to predict novel sequence features thereby enabling the successful generation of de novo Ab molecules. Hence, the merging of synthetic Ab design, deep sequencing technologies, and advanced computational models heralds a new chapter in Ab discovery, broadening our comprehension of immunology and streamlining the advancement of biological therapeutics. [ABSTRACT FROM AUTHOR]

Background: In Babitonga Bay, southern Brazil, records of yam consumption exist among shellmound builders from at least 4000 years ago. Shellmounds (sambaquis) are anthropogenic structures in the form of mounds with layers of shells associated with other faunal remains, as well as with charcoal, artefacts and burial. Larger sambaquis are considered to be funerary monuments. The indigenous Jê and Guarani people also lived in the region before the European invasion and cultivated yams. Currently, exotic and domesticated yams are cultivated in the region by farmers. Our aim is to describe the long-term history between the people and Dioscorea in the Babitonga Bay region based on its consumption and occurrence in shellmounds and swiddens. Methods: Surveys of Dioscorea spp. and host were carried out in the vegetation of shellmounds and in the surrounding area using visual detection through intensive searches in transects using the walking method. The survey of Dioscorea species used and cultivated in the precolonial, colonial and current periods was carried out based on the literature. In the present study, only Dioscorea trifida cultivations were recorded. Results: Dioscorea cayennensis, Dioscorea chondrocarpa, Dioscorea dodecaneura, Dioscorea laxiflora, Dioscorea olfersiana, and Dioscorea scabra, all recorded in associated vegetation of shellmounds, in different combinations of the species. In swiddens, D. trifida is most common, followed by Dioscorea alata and, to a lesser extent, Dioscorea bulbifera and D. cayennensis. Records of food use prevail, but they are used as medicinal plants. Yams are integrated on anthropogenic soils of shellmounds and in swiddens in monoculture systems or in intercropping with Zea mays or Colocasia esculenta. The presence of exotic food trees and D. cayennensis in some shellmounds indicates the influence of colonizers on the composition of the vegetation. In sambaquis, there are overlapping processes of construction of cultural niches by different human groups at different times. Conclusions: The sambaquis and the associated vegetation and swiddens form part of a domesticated landscape. The native species of Dioscorea recorded in shellmounds and surrounding vegetation do not depend on human action to perpetuate themselves in the environment. However, this does not rule out human influence in the past, but it does not indicate horticulture among the Sambaquianos. Greater investment in genetic, archaeobotanical and ethnobotanical research can contribute to a better understanding of the relationship between people and yams over thousands of years. [ABSTRACT FROM AUTHOR]

Background: Though persons of African descent have one of the widest genetic variability, genetic polymorphisms of drug-metabolising enzymes such as N-Acetyltransferase-2 (NAT2) are understudied. This study aimed to identify prevalent NAT2 single nucleotide polymorphisms (SNPs) and infer their potential effects on enzyme function among Kenyan volunteers with tuberculosis (TB) infection. Genotypic distribution at each SNP and non-random association of alleles were evaluated by testing for Hardy-Weinberg Equilibrium (HWE) and Linkage Disequilibrium (LD). Methods: We isolated genomic DNA from cryopreserved Peripheral Blood Mononuclear Cells of 79 volunteers. We amplified the protein-coding region of the NAT2 gene by polymerase chain reaction (PCR) and sequenced PCR products using the Sanger sequencing method. Sequencing reads were mapped and aligned to the NAT2 reference using the Geneious software (Auckland, New Zealand). Statistical analyses were performed using RStudio version 4.3.2 (2023.09.1 + 494). Results: The most frequent haplotype was the wild type NAT2*4 (37%). Five genetic variants: 282C > T (NAT2*13), 341 T > C (NAT2*5), 803A > G (NAT2*12), 590G > A (NAT2*6) and 481C > T (NAT2*11) were observed with allele frequencies of 29%, 18%, 6%, 6%, and 4% respectively. According to the bimodal distribution of acetylation activity, the predicted phenotype was 76% rapid (mainly consisting of the wildtype NAT2*4 and the NAT2*13A variant). A higher proportion of rapid acetylators were female, 72% vs 28% male (p = 0.022, odds ratio [OR] 3.48, 95% confidence interval [CI] 1.21 to 10.48). All variants were in HWE. NAT2 341 T > C was in strong complete LD with the 590G > A variant (D′ = 1.0, r2 = − 0.39) but not complete LD with the 282C > T variant (D′ = 0.94, r2 = − 0.54). Conclusion: The rapid acetylation haplotypes predominated. Despite the LD observed, none of the SNPs could be termed tag SNP. This study adds to the genetic characterisation data of African populations at NAT2, which may be useful for developing relevant pharmacogenomic tools for TB therapy. To support optimised, pharmacogenomics-guided TB therapy, we recommend genotype-phenotype studies, including studies designed to explore gender-associated differences. [ABSTRACT FROM AUTHOR]

Background: Thymic epithelial tumors (TETs) are the most common primary neoplasms of the anterior mediastinum. Different risk subgroups of TETs have different prognosis and therapeutic strategies, therefore, preoperative identification of different risk subgroups is of high clinical significance. This study aims to explore the diagnostic efficiency of quantitative computed tomography (CT) parameters combined with preoperative systemic inflammatory markers in differentiating low-risk thymic epithelial tumors (LTETs) from high-risk thymic epithelial tumors (HTETs). Methods: 74 Asian patients with TETs confirmed by biopsy or postoperative pathology between January 2013 and October 2022 were collected retrospectively and divided into two risk subgroups: LTET group (type A, AB and B1 thymomas) and HTET group (type B2, B3 thymomas and thymic carcinoma). Statistical analysis were performed between the two groups in terms of quantitative CT parameters and preoperative systemic inflammatory markers. Multivariate logistic regression analysis was used to determine the independent predictors of risk subgroups of TETs. The area under curve (AUC) and optimal cut-off values were calculated by receiver operating characteristic (ROC) curves. Results: 47 TETs were in LTET group, while 27 TETs were in HTET group. In addition to tumor size and CT value of the tumor on plain scan, there were statistical significance comparing in CT value of the tumor on arterial phase (CTv-AP) and venous phase (CTv-VP), and maximum enhanced CT value (CEmax) of the tumor between the two groups (for all, P < 0.05). For systemic inflammatory markers, HTET group was significantly higher than LTET group (for all, P < 0.05), including platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR) and systemic immune-inflammation index (SII). Multivariate logistic regression analysis showed that NLR (odds ratio [OR] = 2.511, 95% confidence interval [CI]: 1.322–4.772, P = 0.005), CTv-AP (OR = 0.939, 95%CI: 0.888–0.994, P = 0.031) and CTv-VP (OR = 0.923, 95%CI: 0.871–0.979, P = 0.008) were the independent predictors of risk subgroups of TETs. The AUC value of 0.887 for the combined model was significantly higher than NLR (0.698), CTv-AP (0.800) or CTv-VP (0.811) alone. The optimal cut-off values for NLR, CTv-AP and CTv-VP were 2.523, 63.44 Hounsfeld Unit (HU) and 88.29HU, respectively. Conclusions: Quantitative CT parameters and preoperative systemic inflammatory markers can differentiate LTETs from HTETs, and the combined model has the potential to improve diagnostic efficiency and to help the patient management. [ABSTRACT FROM AUTHOR]

Background: The complexity of the Chagas disease and its phases is impossible to have a unique test for both phases and a lot of different epidemiological scenarios. Currently, serology is the reference standard technique; occasionally, results are inconclusive, and a different diagnostic technique is needed. Some guidelines recommend molecular testing. A systematic review and meta-analysis of available molecular tools/techniques for the diagnosis of Chagas disease was performed to measure their heterogeneity and efficacy in detecting Trypanosoma cruzi infection in blood samples. Methods: A systematic review was conducted up to July 27, 2022, including studies published in international databases. Inclusion and exclusion criteria were defined to select eligible studies. Data were extracted and presented according to PRISMA 2020 guidelines. Study quality was assessed using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2). A random-effects model was used to calculate pooled sensitivity, specificity, and diagnostic odds ratio (DOR). Forest plots and a summary of the receiving operating characteristics (SROC) curves displayed the outcomes. Heterogeneity was determined by I2 and Tau2 statistics and P values. Funnel plots and Deek's test were used to assess publication bias. A quantitative meta-analysis of the different outcomes in the two different clinical phases was performed. Results: We identified 858 records and selected 32 papers. Studies pertained to endemic countries and nonendemic areas with adult and paediatric populations. The sample sizes ranged from 17 to 708 patients. There were no concerns regarding the risk of bias and applicability of all included studies. A positive and nonsignificant correlation coefficient (S = 0.020; P = 0.992) was obtained in the set of studies that evaluated diagnostic tests in the acute phase population (ACD). A positive and significant correlation coefficient (S = 0.597; P < 0.000) was obtained in the case of studies performed in the chronic phase population (CCD). This resulted in high heterogeneity between studies, with the master mix origin and guanidine addition representing significant sources. Interpretation/Conclusions and relevance: The results described in this meta-analysis (qualitative and quantitative analyses) do not allow the selection of the optimal protocol of molecular method for the study of Trypanosoma cruzi infection in any of its phases, among other reasons due to the complexity of this infection. Continuous analysis and optimization of the different molecular techniques is crucial to implement this efficient diagnosis in endemic areas. [ABSTRACT FROM AUTHOR]

Background: Verticillium wilt, caused by the fungus Verticillium dahliae, leads to significant losses in cotton yield worldwide. Biocontrol management is a promising means of suppressing verticillium wilt. The purpose of the study was to obtain and analyze endophytic bacteria with Verticillium wilt-resistant activities from the roots of Gossypium barbadense 'Xinhai15' and to explore the interactions between the soil and plants. Results: An endophytic bacterium Bacillus sp. T6 was obtained from the Verticillium wilt-resistant cotton G. barbadense 'Xinhai15', which showed significant antagonistic abilities against cotton Verticillium wilt. The bioassay results indicated that the strain possessed strong antagonistic abilities that inhibited V. dahliae spore germination and mycelial growth without contact, and thus it was speculated that the active factor of the bacteria might be volatile compounds. A total of 46 volatile substances were detected via headspace solid-phase microextraction and gas chromatography–mass spectrometry analysis. The pure product verification experiment confirmed that the styrene produced by the T6 strain was the main virulence factor. Transcriptome analysis showed that following styrene induction, 247 genes in V. dahliae, including four hydrolase genes, eight dehydrogenase genes, 11 reductase genes, 17 genes related to transport and transfer were upregulated. Additionally, 72 genes, including two chitinase genes, two protease genes, five transport-related genes, and 33 hypothetical protein genes, were downregulated. The quantitative real-time PCR results confirmed that the expression of the four genes VDAG_02838, VDAG_09554, VDAG_045572, and VDAG_08251 was increased by 3.18, 78.83, 2.71, and 2.92 times, respectively, compared with the uninduced control group. Conclusions: The research provides a new reference for the development and application of the volatile compounds of endophytic bacteria as new biocontrol agents for the control of Verticillium wilt and as biological preservatives for agricultural products. [ABSTRACT FROM AUTHOR]

Background: Trypanosomatids are among the most critical parasites for public health due to their impact on human, animal, and plant health. Diseases associated with these pathogens manifest mainly in poor and vulnerable populations, where social, environmental, and biological factors modulate the case incidence and geographical distribution. Methods: We used Sanger and amplicon-based next-generation sequencing (NGS) in samples from different mammals to identify trypanosomatid infections in several departments in Colombia. A total of 174 DNA samples (18 humans, 83 dogs, and 73 wild mammals) were analyzed by conventional PCR using a fragment of the heat shock protein 70 (Hsp70) gene and Sanger sequenced the positive samples. Twenty-seven samples were sent for amplicon-based NGS using the same gene fragment. Data obtained were used to perform diversity analyses. Results: One hundred and thirteen samples were positive for PCR by Hsp70 fragment; these corresponded to 22.1% Leishmania spp., 18.6% L. amazonensis, 9.7% L. braziliensis, 14.2% L. infantum, 8% L. panamensis, and 27.4% Trypanosoma cruzi. Comparison of the identified species by the two sequencing technologies used resulted in 97% concordance. Alpha and beta diversity indices were significant, mainly for dogs; there was an interesting index of coinfection events in the analyzed samples: different Leishmania species and the simultaneous presence of T. cruzi and even T. rangeli in one of the samples analyzed. Moreover, a low presence of L. braziliensis was observed in samples from wild mammals. Interestingly, to our knowledge, this is the first report of Leishmania detection in Hydrochaeris hydrochaeris (capybara) in Colombia. Conclusions: The Hsp70 fragment used in this study is an optimal molecular marker for trypanosomatid identification in many hosts and allows the identification of different species in the same sample when amplicon-based sequencing is used. However, the use of this fragment for molecular diagnosis through conventional PCR should be carefully interpreted because of this same capacity to identify several parasites. This point is of pivotal importance in highly endemic countries across South America because of the co-circulation of different genera from the Trypanosomatidae family. The findings show an interesting starting point for One Health approaches in which coevolution and vector-host interactions can be studied. [ABSTRACT FROM AUTHOR]

Background: As currently defined, recent small subcortical infarcts (RSSI) do not have a lower size boundary, and the smallest diffusion-weighted imaging (DWI) infarcts, which we term acute subcortical cerebral microinfarcts (As-CMI) with lesion diameter less than 5 mm, might have clinical implications distinct from RSSI. We aimed to investigate the distinct characteristics of As-CMI as compared to the larger size of RSSI regarding vascular risk factors, clinical manifestation, radiological markers of SVD distribution, and outcomes.Methods: In a consecutive cohort, patients were selected with a magnetic resonance DWI-confirmed RSSI between January 2010 and November 2020. We measured axial infarct diameter and classified patients into two groups: The As-CMI group (diameter < 5 mm) versus the Larger RSSI group (diameter 5-20 mm). Clinical variables, including vascular risk factors, clinical symptoms/signs, lesion locations, and radiological markers of cerebral small vessel disease (SVD) on MRI were analyzed between the two groups. Patients were followed up for 12 months and functional outcomes were measured by the modified ranking scale (mRS).Results: In a total of 584 patients with RSSI, 23 (3.9%) were defined as As-CMI. The most common neurological deficits with As-CMI were hemiparalysis (n = 20), followed by central facial/lingual palsy (n = 10) and hemidysesthesia (n = 10). Most As-CMIs were located in the basal ganglia (n = 11), followed by the thalamus (n = 5) and centrum semiovale (n = 4). No different regional distributions and symptoms/signs frequencies were found between the two groups except for a lower percentage of dysarthria in the As-CMI group (p = 0.008). In a multivariate analysis, patients with As-CMI were independently associated with the presence of lacunes (adjusted odds ratio [aOR] 2.88; 95% confidence interval [CI] 1.21-6.84), multiple lacunes (aOR 3.5, CI 1.29-9.48) and higher total SVD burden (aOR 1.68, CI 1.11-2.53). Patients with As-CMI did not show a better functional outcome after 12 months of follow-up.Conclusions: Patients with As-CMI had a non-specific clinical profile but a higher burden of SVD, indicating As-CMI might be s sign of more severe small vascular injury. Whether its vascular features are associated with worse cognitive outcomes requires further investigation. [ABSTRACT FROM AUTHOR]

Background: Hepatocyte nuclear factor 4α (HNF4α) and glucocorticoid receptor (GR), master regulators of liver metabolism, are down-regulated in fatty liver diseases. The present study aimed to elucidate the role of down-regulation of HNF4α and GR in fatty liver and hyperlipidemia. Methods: Adult mice with liver-specific heterozygote (HET) and knockout (KO) of HNF4α or GR were fed a high-fat-high-sugar diet (HFHS) for 15 days. Alterations in hepatic and circulating lipids were determined with analytical kits, and changes in hepatic mRNA and protein expression in these mice were quantified by real-time PCR and Western blotting. Serum and hepatic levels of bile acids were quantified by LC-MS/MS. The roles of HNF4α and GR in regulating hepatic gene expression were determined using luciferase reporter assays. Results: Compared to HFHS-fed wildtype mice, HNF4α HET mice had down-regulation of lipid catabolic genes, induction of lipogenic genes, and increased hepatic and blood levels of lipids, whereas HNF4α KO mice had fatty liver but mild hypolipidemia, down-regulation of lipid-efflux genes, and induction of genes for uptake, synthesis, and storage of lipids. Serum levels of chenodeoxycholic acid and deoxycholic acid tended to be decreased in the HNF4α HET mice but dramatically increased in the HNF4α KO mice, which was associated with marked down-regulation of cytochrome P450 7a1, the rate-limiting enzyme for bile acid synthesis. Hepatic mRNA and protein expression of sterol-regulatory-element-binding protein-1 (SREBP-1), a master lipogenic regulator, was induced in HFHS-fed HNF4α HET mice. In reporter assays, HNF4α cooperated with the corepressor small heterodimer partner to potently inhibit the transactivation of mouse and human SREBP-1C promoter by liver X receptor. Hepatic nuclear GR proteins tended to be decreased in the HNF4α KO mice. HFHS-fed mice with liver-specific KO of GR had increased hepatic lipids and induction of SREBP-1C and PPARγ, which was associated with a marked decrease in hepatic levels of HNF4α proteins in these mice. In reporter assays, GR and HNF4α synergistically/additively induced lipid catabolic genes. Conclusions: induction of lipid catabolic genes and suppression of lipogenic genes by HNF4α and GR may mediate the early resistance to HFHS-induced fatty liver and hyperlipidemia. [ABSTRACT FROM AUTHOR]

Background: The distribution of parasite load across hosts may modify the transmission dynamics of infectious diseases. Chagas disease is caused by a multi-host protozoan, Trypanosoma cruzi, but the association between host parasitemia and infectiousness to the vector has not been studied in sylvatic mammalian hosts. We quantified T. cruzi parasite load in sylvatic mammals, modeled the association of the parasite load with infectiousness to the vector and compared these results with previous ones for local domestic hosts. Methods: The bloodstream parasite load in each of 28 naturally infected sylvatic mammals from six species captured in northern Argentina was assessed by quantitative PCR, and its association with infectiousness to the triatomine Triatoma infestans was evaluated, as determined by natural or artificial xenodiagnosis. These results were compared with our previous results for 88 humans, 70 dogs and 13 cats, and the degree of parasite over-dispersion was quantified and non-linear models fitted to data on host infectiousness and bloodstream parasite load. Results: The parasite loads of Didelphis albiventris (white-eared opossum) and Dasypus novemcinctus (nine-banded armadillo) were directly and significantly associated with infectiousness of the host and were up to 190-fold higher than those in domestic hosts. Parasite load was aggregated across host species, as measured by the negative binomial parameter, k, and found to be substantially higher in white-eared opossums, cats, dogs and nine-banded armadillos (range: k = 0.3–0.5) than in humans (k = 5.1). The distribution of bloodstream parasite load closely followed the "80–20 rule" in every host species examined. However, the 20% of human hosts, domestic mammals or sylvatic mammals exhibiting the highest parasite load accounted for 49, 25 and 33% of the infected triatomines, respectively. Conclusions: Our results support the use of bloodstream parasite load as a proxy of reservoir host competence and individual transmissibility. The over-dispersed distribution of T. cruzi bloodstream load implies the existence of a fraction of highly infectious hosts that could be targeted to improve vector-borne transmission control efforts toward interruption transmission. Combined strategies that decrease the parasitemia and/or host–vector contact with these hosts would disproportionally contribute to T. cruzi transmission control. [ABSTRACT FROM AUTHOR]

Tankyrase 1 (TNKS1) and tankyrase 2 (TNKS2) are two homologous proteins that are gaining increasing importance due to their implication in multiple pathways and diseases such as cancer. TNKS1/2 interact with a large variety of substrates through the ankyrin (ANK) domain, which recognizes a sequence present in all the substrates of tankyrase, called Tankyrase Binding Motif (TBM). One of the main functions of tankyrases is the regulation of protein stability through the process of PARylation-dependent ubiquitination (PARdU). Nonetheless, there are other functions less studied that are also essential in order to understand the role of tankyrases in many pathways. In this review, we concentrate in different tankyrase substrates and we analyze in depth the biological consequences derived of their interaction with TNKS1/2. We also examine the concept of both canonical and non-canonical TBMs and finally, we focus on the information about the role of TNKS1/2 in different tumor context, along with the benefits and limitations of the current TNKS inhibitors targeting the catalytic PARP domain and the novel strategies to develop inhibitors against the ankyrin domain. Available data indicates the need for further deepening in the knowledge of tankyrases to elucidate and improve the current view of the role of these PARP family members and get inhibitors with a better therapeutic and safety profile. [ABSTRACT FROM AUTHOR]

Dairy cattle undergo dramatic metabolic, endocrine, physiologic and immune changes during the peripartal period largely due to combined increases in energy requirements for fetal growth and development, milk production, and decreased dry matter intake. The negative nutrient balance that develops results in body fat mobilization, subsequently leading to triacylglycerol (TAG) accumulation in the liver along with reductions in liver function, immune dysfunction and a state of inflammation and oxidative stress. Mobilization of muscle and gluconeogenesis are also enhanced, while intake of vitamins and minerals is decreased, contributing to metabolic and immune dysfunction and oxidative stress. Enhancing post-ruminal supply of methyl donors is one approach that may improve immunometabolism and production synergistically in peripartal cows. At the cellular level, methyl donors (e.g. methionine, choline, betaine and folic acid) interact through one-carbon metabolism to modulate metabolism, immune responses and epigenetic events. By modulating those pathways, methyl donors may help increase the export of very low-density lipoproteins to reduce liver TAG and contribute to antioxidant synthesis to alleviate oxidative stress. Thus, altering one-carbon metabolism through methyl donor supplementation is a viable option to modulate immunometabolism during the peripartal period. This review explores available data on the regulation of one-carbon metabolism pathways in dairy cows in the context of enzyme regulation, cellular sensors and signaling mechanisms that might respond to increased dietary supply of specific methyl donors. Effects of methyl donors beyond the one-carbon metabolism pathways, including production performance, immune cell function, mechanistic target or rapamycin signaling, and fatty acid oxidation will also be highlighted. Furthermore, the effects of body condition and feeding system (total mixed ration vs. pasture) on one-carbon metabolism pathways are explored. Potential effects of methyl donor supply during the pepartum period on dairy calf growth and development also are discussed. Lastly, practical nutritional recommendations related to methyl donor metabolism during the peripartal period are presented. Nutritional management during the peripartal period is a fertile area of research, hence, underscoring the importance for developing a systems understanding of the potential immunometabolic role that dietary methyl donors play during this period to promote health and performance. [ABSTRACT FROM AUTHOR]

Background: Periodontitis is associated with cardiovascular mortality in the general population and adults with chronic diseases. However, it is unclear whether periodontitis predicts survival in the setting of kidney failure.Methods: ORAL-D was a propensity matched analysis in 3338 dentate adults with end-stage kidney disease treated in a hemodialysis network in Europe and South America designed to examine the association between periodontitis and all-cause and cardiovascular-related mortality in people on long-term hemodialysis. Participants were matched 1:1 on their propensity score for moderate to severe periodontitis assessed using the World Health Organization Community Periodontal Index. A random-effects Cox proportional hazards model was fitted with shared frailty to account for clustering of mortality risk within countries.Results: Among the 3338 dentate participants, 1355 (40.6%) had moderate to severe periodontitis at baseline. After using propensity score methods to generate a matched cohort of participants with periodontitis similar to those with none or mild periodontal disease, moderate to severe periodontitis was associated with a lower risk of all-cause (9.1 versus 13.0 per 100 person years, hazard ratio 0.74, 95% confidence interval 0.61 to 0.90) and cardiovascular (4.3 versus 6.9 per 100 person years, hazard ratio 0.67, 0.51 to 0.88) mortality. These associations were not changed substantially when participants were limited to those with 12 or more natural teeth and when accounting for competing causes of cardiovascular death.Conclusion: In contrast to the general population, periodontitis does not appear to be associated with an increased risk of early death in adults treated with hemodialysis. [ABSTRACT FROM AUTHOR]

Background: Understanding how people interpret environmental change and develop practices in response to such change is essential to comprehend human resource use. In the cosmology of the American indigenous peoples, as among the Mapuche people, freshwater systems are considered a living entity, where animals have an enormous role to play in the universe of meaning. However, human adaptive responses to freshwater system dynamics are scarcely examined. In this work a survey is carried out in three Mapuche communities of Argentine Patagonia to assess their traditional knowledge of the fishes and other non-human living beings that inhabit lakes and rivers. Both material and symbolic aspects are included, as are the differences in knowledge and use of the fishes between past and present times. Methods: Our methods were based on a quali-quantitative fieldwork approach. In-depth interviews were carried out with 36 individuals from three rural Mapuche populations in Neuquén province (Patagonia, Argentina). Free listing was used for inquiring about fish knowledge and use. Fishes were identified scientifically and ethnotaxonomically. In-depth analysis of the discourses was conducted, documenting the recognition, perception, and cultural significance of fluvial environments and their inhabitants. Quantitative survey results were analyzed with categorical statistical methods. Results: The body of knowledge of the communities studied reflects the socio-environmental changes experienced by Patagonian freshwater bodies. According to local perception, non-human beings live in these water bodies, guarding the environment, and they should not be disturbed. At present, five different fish species are identified, three of which are exotic, having been introduced at the beginning of the 20th century by the white man. These exotic trout (Oncorhynchus mykiss and Salvelinus fontinalis) are considered ill omens, indicators of the white man's presence, and therefore their appearance presages negative events for the families. In addition, we found that Mapuche people differentiate fish species mainly by morphological, organoleptic and ecological attributes. Current consumption of fish by Mapuche communities is sporadic, in accordance with bibliography and ancient tales. Several fishing tools are used, including modern elements. Conclusions: Our data enable us to characterise dynamic traditional knowledge in these communities, which is flexible in nature and adaptable to new situations, demonstrated by the incorporation not only of new species but also new fishing tools. It also seems that new significances become absorbed in synchrony with the advance or arrival of exotic and invasive species. For the Mapuche, the presence of the white man heralded by exotic trouts speaks of how a recent event, such as the introduction of the salmonids, is already incorporated into Mapuche symbolism. Mapuche traditional knowledge and cosmovision on the use of fish and waters, a vision which promotes respect and the avoidance of actions that could disturb the beings (animals and sacred or mythological characters) that inhabit and take care of them should be fostered as part of management plans of regional natural resources. This paper contributes to the broader literature on freshwater resource management by providing empirical evidence of the critical role of local perceptions in promoting the sustainable management of natural resources. [ABSTRACT FROM AUTHOR]

Background: Trypanosoma cruzi is the causative agent of Chagas disease. Due to its genetic diversity has been classified into six Discrete Typing Units (DTUs) in association with transmission cycles. In Colombia, natural T. cruzi infection has been detected in 15 triatomine species. There is scarce information regarding the infection rates, DTUs and feeding preferences of secondary vectors. Therefore, the aim of this study was to determine T. cruzi infection rates, parasite DTU, ecotopes, insect stages, geographical location and bug feeding preferences across six different triatomine species. Methods: A total of 245 insects were collected in seven departments of Colombia. We conducted molecular detection and genotyping of T. cruzi with subsequent identification of food sources. The frequency of infection, DTUs, TcI genotypes and feeding sources were plotted across the six species studied. A logistic regression model risk was estimated with insects positive for T. cruzi according to demographic and eco-epidemiological characteristics. Results: We collected 85 specimens of Panstrongylus geniculatus, 77 Rhodnius prolixus, 37 R. pallescens, 34 Triatoma maculata, 8 R. pictipes and 4 T. dimidiata. The overall T. cruzi infection rate was 61.2% and presented statistical associations with the departments Meta (OR: 2.65; 95% CI: 1.69-4.17) and Guajira (OR: 2.13; 95% CI: 1.16-3.94); peridomestic ecotope (OR: 2.52: 95% CI: 1.62-3.93); the vector species P. geniculatus (OR: 2.40; 95% CI: 1.51-3.82) and T. maculata (OR: 2.09; 95% CI: 1.02-4.29); females (OR: 2.05; 95% CI: 1.39-3.04) and feeding on opossum (OR: 3. 15; 95% CI: 1.85-11.69) and human blood (OR: 1.55; 95% CI: 1.07-2.24). Regarding the DTUs, we observed TcI (67. 3%), TcII (6.7%), TcIII (8.7%), TcIV (4.0%) and TcV (6.0%). Across the samples typed as TcI, we detected TcIDom (19%) and sylvatic TcI (75%). The frequencies of feeding sources were 59.4% (human blood); 11.2% (hen); 9.6% (bat); 5.6% (opossum); 5.1% (mouse); 4.1% (dog); 3.0% (rodent); 1.0% (armadillo); and 1.0% (cow). Conclusions: New scenarios of T. cruzi transmission caused by secondary and sylvatic vectors are considered. The findings of sylvatic DTUs from bugs collected in domestic and peridomestic ecotopes confirms the emerging transmission scenarios in Colombia. [ABSTRACT FROM AUTHOR]

Background: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths. The average survival and 5-year survival rates of HCC patients still remains poor. Thus, there is an urgent need to better understand the mechanisms of cancer progression in HCC and to identify useful biomarkers to predict prognosis. Methods: Public data portals including Oncomine, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) profiles were used to retrieve the HCC-related microarrays and to identify potential genes contributed to cancer progression. Bioinformatics analyses including pathway enrichment, protein/gene interaction and text mining were used to explain the potential roles of the identified genes in HCC. Quantitative real-time polymerase chain reaction analysis and Western blotting were used to measure the expression of the targets. The data were analysed by SPSS 20. 0 software. Results: We identified 80 genes that were significantly dysregulated in HCC according to four independent microarrays covering 386 cases of HCC and 327 normal liver tissues. Twenty genes were consistently and stably dysregulated in the four microarrays by at least 2-fold and detection of gene expression by RT-qPCR and western blotting showed consistent expression profiles in 11 HCC tissues compared with corresponding paracancerous tissues. Eleven of these 20 genes were associated with disease-free survival (DFS) or overall survival (OS) in a cohort of 157 HCC patients, and eight genes were associated with tumour pathologic PT, tumour stage or vital status. Potential roles of those 20 genes in regulation of HCC progression were predicted, primarily in association with metastasis. INTS8 was specifically correlated with most clinical characteristics including DFS, OS, stage, metastasis, invasiveness, diagnosis, and age. Conclusion: The significantly dysregulated genes identified in this study were associated with cancer progression and prognosis in HCC, and might be potential therapeutic targets for HCC treatment or potential biomarkers for diagnosis and prognosis. [ABSTRACT FROM AUTHOR]

Background: People with end-stage kidney disease treated with dialysis experience high rates of premature death that are at least 30-fold that of the general population, and have markedly impaired quality of life. Despite this, interventions that lower risk factors for mortality (including antiplatelet agents, epoetins, lipid lowering, vitamin D compounds, or dialysis dose) have not been shown to improve clinical outcomes for this population. Although mortality outcomes may be improving overall, additional modifiable determinants of health in people treated with dialysis need to be identified and evaluated. Oral disease is highly prevalent in the general population and represents a potential and preventable cause of poor health in dialysis patients. Oral disease may be increased in patients treated with dialysis due to their lower uptake of public dental services, as well as increased malnutrition and inflammation, although available exploratory data are limited by small sample sizes and few studies evaluating links between oral health and clinical outcomes for this group, including mortality and cardiovascular disease. Recent data suggest periodontitis may be associated with mortality in dialysis patients and well-designed, larger studies are now required. Methods/design: The ORAL Diseases in hemodialysis (ORAL-D) study is a multinational, prospective (minimum follow-up 12 months) study. Participants comprise consecutive adults treated with long-term in-center hemodialysis. Between July 2010 and February 2012, we recruited 4500 dialysis patients from randomly selected outpatient dialysis clinics in Europe within a collaborative network of dialysis clinics administered by a dialysis provider, Diaverum, in Europe (France, Hungary, Italy, Poland, Portugal, and Spain) and South America (Argentina). At baseline, dental surgeons with training in periodontology systematically assessed the prevalence and characteristics of oral disease (dental, periodontal, mucosal, and salivary) in all participants. Oral hygiene habits and thirst were evaluated using self-administered questionnaires. Data for hospitalizations and mortality (total and cause-specific) according to baseline oral health status will be collected once a year until 2022. Discussion: This large study will estimate the prevalence, characteristics and correlations of oral disease and clinical outcomes (mortality and hospitalization) in adults treated with dialysis. We will further evaluate any association between periodontitis and risk of premature death in dialysis patients that has been suggested by existing research. The results from this study should provide powerful new data to guide strategies for future interventional studies for preventative and curative oral disease strategies in adults who have end-stage kidney disease. [ABSTRACT FROM AUTHOR]

Background: Human serum paraoxonase 1 (PON1) plays a major role in the metabolism of several organophosphorus compounds. The enzyme is encoded by the polymorphic gene PON1, located on chromosome 7q21.3. Aiming to identify genetic variations related to the risk of developing brain tumors, we investigated the putative association between common nonsynonymous PON1 polymorphisms and the risk of developing astrocytoma and meningioma. Methods: Seventy one consecutive patients with brain tumors (43 with astrocytoma grade II/III and 28 with meningioma) with ages ranging 21 to 76 years, and 220 healthy controls subjects were analyzed for the frequency of the nonsynonymous PON1 genotypes L55M rs854560 and Q192R rs662. All participants were adult Caucasian individuals recruited in the central area of Spain. Results: The frequencies of the PON1 genotypes and allelic variants of the polymorphisms PON1 L55M and PON1 Q192R did not differ significantly between patients with astrocytoma and meningioma and controls. The minor allele frequencies were as follows: PON1 55L, 0.398, 0.328 and 0.286 for patients with astrocytoma, meningioma and control individuals, respectively; PON1 192R, 0.341, 0.362 and 0.302 for patients with astrocytoma, meningioma and control individuals, respectively. Correction for age, gender, or education, made no difference in odds ratios and the p values remained non-significant. Haplotype association analyses did not identify any significant association with the risk of developing astrocytoma or meningioma. Conclusions: Common nonsynonymous PON1 polymorphisms are not related with the risk of developing astrocytoma and meningioma. [ABSTRACT FROM AUTHOR]

Background: N-acetyltransferase type 2 (Nat2) is a phase II drug- metabolizing enzyme that plays a key role in the bioactivation of aromatic and heterocyclic amines. Its relevance in drug metabolism and disease susceptibility remains a central theme for pharmacogenetic research, mainly because of its genetic variability among human populations. In fact, the evolutionary and ethnic-specific SNPs on the NAT2 gene remain a focus for the potential discoveries in personalized drug therapy and genetic markers of diseases. Despite the wide characterization of NAT2 SNPs frequency in established ethnic groups, little data are available for highly admixed populations. In this context, five common NAT2 SNPs (G191A, C481T, G590A, A803G and G857A) were investigated in a highly admixed population comprised of Afro-Brazilians, Whites, and Amerindians in northeastern Brazil. Thus, we sought to determine whether the distribution of NAT2 polymorphism is different among these three ethnic groups. Results: Overall, there were no statistically significant differences in the distribution of NAT2 polymorphism when Afro-Brazilian and White groups were compared. Even the allele frequency of 191A, relatively common in African descendents, was not different between the Afro-Brazilian and White groups. However, allele and genotype frequencies of G590A were significantly higher in the Amerindian group than either in the Afro-Brazilian or White groups. Interestingly, a haplotype block between G590A and A803G was verified exclusively among Amerindians. Conclusions: Our results indicate that ethnic admixture might contribute to a particular pattern of genetic diversity in the NAT2 gene and also offer new insights for the investigation of possible new NAT2 geneenvironment effects in admixed populations. [ABSTRACT FROM AUTHOR]

Background: Changes in the density and expression of histamine receptors (HRH) have been detected in Parkinson's disease (PD) patients, and HRH antagonists bring about improvements in motor and other symptoms, thus suggesting that HRH play a role in the clinical response of PD patients. This study is aimed to analyse polymorphic variations of HRH in patients with PD. Methods: Leukocytary DNA from 195 PD patients and a control group of 231 unrelated healthy individuals was studied for the nonsynonymous HRH1Leu449Ser and the promoter HRH2G-1018A polymorphisms by using amplification-restriction analyses. Results: The HRH1Leu449Ser amino acid substitution was identified in two women with lateonset PD whereas it was not observed among healthy subjects. The HRH2G-1018A polymorphism was observed with allele frequencies = 3.59 (95% CI = 1.74-5.44) and 5.0 (95% CI = 3.00-6.96) for patients with PD and healthy controls, respectively. These frequencies were independent of gender and age of onset of the disease. Multiple comparison analyses revealed that differences were not statistically significant. Conclusion: These results indicate that the polymorphisms analyzed are not a major risk factor for PD, although the HRH1Leu449Ser amino acid substitution might be related to PD. [ABSTRACT FROM AUTHOR]

Background: Drug-metabolizing enzymes play a role in chemical carcinogenesis through enzymatic activation of procarcinogens to biologically reactive metabolites. The role of gene polymorphisms of several cytochrome P450 enzymes in digestive cancer risk has been extensively investigated. However, the drug-metabolizing enzymes with the broader substrate specificity, CYP3A4 and CYP3A5, have not been analyzed so far. This study aims to examine associations between common CYP3A4 and CYP3A5 polymorphisms and digestive cancer risk. Methods: CYP3A4 and CYP3A5 genotypes were determined in 574 individuals including 178 patients with primary liver cancer, 82 patients with gastric cancer, 151 patients with colorectal cancer, and 163 healthy individuals. Results: The variant allele frequencies for patients with liver cancer, gastric cancer, colorectal cancer and healthy controls, respectively, were: CYP3A4*1B, 4.8 % (95% C.I. 2.6-7.0), 3.7 % (0.8-6.6) 4.3% (2.0-6.6) and 4.3% (2.1-6.5); CYP3A5*3, 91.8 % (93.0-97.4), 95.7% (92.6-98.8), 91.7% (88.6-94.8) and 90.8% (87.7-93.9). The association between CYP3A4*1B and CYP3A5*3 variant alleles did not significantly differ among patients and controls. No differences in genotypes, allele frequencies, or association between variant alleles were observed with regard to gender, age at diagnosis, tumour site or stage. Conclusion: Common polymorphisms on CYP3A4 and CYP3A5 genes do not modify the risk of developing digestive cancers in Western Europe. [ABSTRACT FROM AUTHOR]

Background: N-acetyltransferase 2 is phase II metabolizing enzyme that participates in the bioconversion of heterocyclic arylamines into electrophilic nitrenium ions, which are important ultimate carcinogens that are directly implicated in tumor initiation process. This study was conducted to examine; (1) whether the N-acetyltransferase 2 (NAT2) genotype is a risk factor for prostate cancer, (2) to study effect of NAT2 genotype on modifying prostate cancer risk from tobacco use. Methods: The case control study was undertaken over a period of 28 months and included 130 prostate cancer patients (CaP) and 140 controls. The NAT2 genotypes were identified by PCRRFLP method in DNA extracted from peripheral blood. Genotype frequencies and the association of genotypes with patients and control groups were assessed by logistic regression model. Results: We observed non-significant association of rapid acetylator genotype NAT2 (OR = 1.452, 95% CI: 0.54-1.87, P = 0.136) in prostate cancer patients. However significant association was observed between rapid acetylator genotype NAT2 and CaP tobacco users (OR = 3.43, 95% CI: 1.68-7.02, P-value < 0.001) when compared with controls. Conclusion: The data suggests that the NAT2 rapid acetylator genotypes may play an important role in determining the risk of developing prostate cancer particularly in the tobacco users of north Indian population. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have attempted to relate genetic polymorphisms within the Nacetyltransferase 2 gene (NAT2) to interindividual differences in response to drugs or in disease susceptibility. However, genotyping of individuals single-nucleotide polymorphisms (SNPs) alone may not always provide enough information to reach these goals. It is important to link SNPs in terms of haplotypes which carry more information about the genotype-phenotype relationship. Special analytical techniques have been designed to unequivocally determine the allocation of mutations to either DNA strand. However, molecular haplotyping methods are labour-intensive and expensive and do not appear to be good candidates for routine clinical applications. A cheap and relatively straightforward alternative is the use of computational algorithms. The objective of this study was to assess the performance of the computational approach in NAT2 haplotypereconstruction from phase-unknown genotype data, for population samples of various ethnic origin. Results: We empirically evaluated the effectiveness of four haplotyping algorithms in predicting haplotype phases at NAT2, by comparing the results with those directly obtained through molecular haplotyping. All computational methods provided remarkably accurate and reliable estimates for NAT2 haplotype frequencies and individual haplotype phases. The Bayesian algorithm implemented in the PHASE program performed the best. Conclusion: This investigation provides a solid basis for the confident and rational use of computational methods which appear to be a good alternative to infer haplotype phases in the particular case of the NAT2 gene, where there is near complete linkage disequilibrium between polymorphic markers. [ABSTRACT FROM AUTHOR]

Background: In the past years, it became apparent that health status and performance differ considerably within dairy farms in Northern Germany. In order to obtain clues with respect to possible causes of these differences, a case-control study was performed. Case farms, which showed signs of health and performance problems, and control farms, which had none of these signs, were compared. Risk factors from different areas such as health management, housing, hygiene and nutrition were investigated as these are known to be highly influential. The aim of this study was to identify major factors within these areas that have the strongest association with health and performance problems of dairy herds in Northern Germany. Results: In the final model, a lower energy density in the roughage fraction of the diet, more pens with dirty lying areas and a low ratio of cows per watering spaces were associated with a higher risk for herd health problems. Moreover, case farms were affected by infections with intestinal parasites, lungworms, liver flukes and Johne's Disease numerically more often than control farms. Case farms more often had pens with raised cubicles compared to the deep bedded stalls or straw yards found in control farms. In general, the hygiene of the floors and beddings was worse in case farms. Concerning nutrition, the microbiological and sensory quality of the provided silages was often insufficient, even in control farms. Less roughage was provided to early lactating cows and the feed was pushed to the feeding fence less frequently in case farms than in control farms. Conclusions: The results show that milk yield and health status were associated with various factors from different areas stressing the importance of all aspects of management for good animal health and performance. Moreover, this study confirmed well-known risk factors for health problems and performance losses. These should better be taken heed of in herd health management. [ABSTRACT FROM AUTHOR]

Introduction: Evidence of kidney damage is observed in children with sickle cell anaemia (SCA) and this continues through adulthood with progression to severe functional impairment in some. One of the earliest features of kidney damage associated with SCA is microalbuminuria. Our objective was to determine the risk factors of microalbuminuria in these children and its relationship with estimated glomerular filtration rate. Methods: This was a cross-sectional and comparative study involving three hundred and twenty three children with SCA in steady state and equal numbers of apparently healthy age and sex matched haemoglobin AA (HbAA) control, aged 6 months to 18 years. They were consecutively recruited over a 6 month period. Result: Microalbuminuria was present in 26% of the study subjects compared with 1.85% of control P = 0.001). Anaemia and high estimated glomerular filtration rate (eGFR) showed strong positive correlation with microalbuminuria (OR = 3.19, CI 0.953–1.116, p = 0.003 and OR = 1.7, CI 1.042–1.066, p = 0.001 respectively). Similarly, eGFR was higher in subjects with SCA than in controls and as well as in those with microalbuminuria compared with those who do not (p = < 0.01). Conclusions: The two most important risk factors for microalbuminuria were anaemia and high eGFR. Age category was associated more with microalbuminuria than just age as a variable. Glomerular filtration rate was higher in children with microalbuminuria than those who do not and it was also higher in children with SCA than in control. [ABSTRACT FROM AUTHOR]

Background: Blastocystis is a stramenopile of worldwide significance due to its capacity to colonize several hosts. Based on its high level of genetic diversity, Blastocystis is classified into global ribosomal subtypes (STs). The aim of this study was to conduct a summary of Blastocystis STs and depict their distribution throughout North and South America; we did this by assembling maps and identifying its most common 18S alleles based on diverse studies that had been reported all over the continent and whose Blastocystis-positive samples were obtained from numerous hosts. Results: Thirty-nine articles relating to nine countries from the American continent were considered, revealing that ST1 (33.3%), ST2 (21.9%), ST3 (37.9%), ST4 (1.7%), ST5 (0.4%), ST6 (1.2%), ST7 (1%), ST8 (0.7%), ST9 (0.4%), ST12 (0.3%), Novel ST (1.1%) and Mixed STs (0.2%) occurred in humans. The STs in other animal hosts were ST1 (6.5%), ST2 (6.5%), ST3 (4.7%), ST4 (7.2%), ST5 (15.9%), ST6 (17.3%), ST7 (3.6%), ST8 (20.6%), ST10 (9%), ST14 (3.6%), ST17 (1.1%) and Novel ST (4%). The countries that presented the most abundant variety of studies reporting STs were the USA with 14 STs, Brazil with 9 STs and Colombia with 8 STs. Additionally, new variants had been described in the last few years, which have increased the prevalence of these subtypes in the countries studied, such as Novel ST (1.1%) and Mixed STs (0.2%) in humans and Novel ST (4%) in animals. Conclusions: This summary updates the epidemiological situation on the distribution of Blastocystis STs in North and South America and will augment current knowledge on the prevalence and genetic diversity of this protozoan. [ABSTRACT FROM AUTHOR]

Background: In 2016, 98% of children in Zimbabwe received breastmilk, however only 40% of babies under six months were exclusively breastfed 24 h prior to data collection. A 2014 survey revealed that Matabeleland South Province had the country's highest starvation rates and food insecurities were rife. This study aimed at investigating maternal, infant, household, environmental and cultural factors influencing exclusive breastfeeding (EBF) practice in Gwanda District. Methods: A cross-sectional study was conducted from January to March 2018. Interviews used pretested structured questionnaires for 225 mothers of infants aged between six and twelve months at immunization outreach points and health facilities. Descriptive statistics, bivariate and multivariate analysis estimated the association between the dependent and independent variables. Exclusive breastfeeding was defined as feeding an infant on breast milk only from birth up to the age of six months. Results: The majority of mothers (n = 193; 89%) had knowledge about EBF and 189 (84%) expressed a positive attitude towards the practice, however, only 81 (36%) practiced exclusive breastfeeding. The most common complementary food/fluid given to the infants was plain water (n = 85; 59%). Predictors for EBF were: maternal Human Immuno-deficiency Virus positive status (Odds Ratio [OR] 0.30; 95% Confidence Interval [CI] 0.17, 0.56) and being economically independent (OR 0.41; 95% CI 0.21, 0.79). Barriers to practicing EBF were: being a young mother under 25 years of age (OR 3.05; 95% CI 1.67, 5.57), having one or two children (OR 2.49; 95% CI 1.29, 4.79), living in less than two rooms (OR 3.86; 95% CI 1.88, 7.93) and having a baby of low birthweight (OR 1.05; 95% CI 0.40, 2.71). After multivariate analysis, only the mother's economic independence was associated with practicing EBF (Adjusted OR [AOR] 0.83; 95% CI 0.30, 0.92). Key informants identified traditional family practices as the major barrier to EBF. Conclusion: The exclusive breastfeeding rates were low despite the mothers' high knowledge levels and positive attitudes towards the practice. In addressing the multiple factors influencing the cost effective practice, there is need to channel supportive measures through a system-wide approach. This can be achieved by realigning breastfeeding policy directives as well as community attitudes and values towards the exclusive breastfeeding. [ABSTRACT FROM AUTHOR]

Background: Parasitic infections, particularly those caused by protozoa, represent a considerable public health problem in developing countries. Blastocystis, Giardia duodenalis, Cryptosporidium spp. and the Entamoeba complex (Entamoeba histolytica, Entamoeba dispar and Entamoeba moshkovskii) are the most common etiological causes of intestinal parasitic infections.Methods: We carried out a descriptive cross-sectional study in school-age children attending a daycare institution in commune eight of Popayán, Cauca (Southwest Colombia). A total of 266 fecal samples were collected (258 from children and eight from pets). Blastocystis, G. duodenalis, Cryptosporidium spp. and the Entamoeba complex were identified by microscopy, quantitative real-time PCR (qPCR) and conventional PCR. The concordance of qPCR and microscopy was assessed using the Kappa index. Molecular characterization was conducted to identify Blastocystis subtypes (18S), G. duodenalis assemblages (tpi and gdh) and Cryptosporidium species/subtypes (18S and GP60). Potential associations between intestinal parasitism and sociodemographic factors were examined using bivariate analyses.Results: A total of 258 fecal samples from children were analyzed by microscopy and 255 samples were analyzed by qPCR. The prevalence of Blastocystis was between 25.19% (microscopy) and 39.22% (qPCR), that of G. duodenalis was between 8.14% (microscopy) and 10.59% (qPCR), that of Cryptosporidium spp. was estimated at 9.8% (qPCR), and that of the Entamoeba complex was between 0.39% (conventional PCR) and 0.78% (microscopy). The concordance between microscopy and qPCR was very low. Blastocystis ST1 (alleles 4, 8, and 80), ST2 (alleles 11, 12, and 15), ST3 (alleles 31, 34, 36, 38,57, and 151), and ST4 (alleles 42 and 91), G. duodenalis assemblages AII, BIII, BIV and D, C. parvum subtype IIa and C. hominis subtype IbA9G3R2 were identified. The only identified member of the Entamoeba complex corresponded to E. histolytica. No statistically significant association was identified between parasitic infection and any sociodemographic variable.Conclusion: This study revealed the usefulness of molecular methods to depict the transmission dynamics of parasitic protozoa in southwest Colombia. The presence of some of these protozoa in domestic animals may be involved in their transmission. [ABSTRACT FROM AUTHOR]

Background: Enteric viruses in surface water pose considerable risk to morbidity in populations living around water catchments and promote outbreaks of waterborne diseases. However, due to poor understanding of the correlation between water quality and the presence of human enteric viruses, the failure to assess viral contamination through alternative viral indicators makes it difficult to control disease transmission.Methods: We investigated the occurrence of Enteroviruses (EnVs), Rotaviruses (HRVs), Astroviruses (AstVs), Noroviruses GII (HuNoVs GII) and Adenoviruses (HAdVs) from Jinhe River over 4 years and analyzed their correlation with physicochemical and bacterial parameters in water samples.Results: The findings showed that all target viruses were detected in water at frequencies of 91.7% for HAdVs, 81.3% for HuNoVs GII, 79.2% for EnVs and AstVs, and 70.8% for HRVs. These viruses had a seasonal pattern, which showed that EnVs were abundant in summer but rare in winter, while HAdVs, HRVs, AstVs, and HuNoVs GII exhibited opposite seasonal trends. Pearson correlation analysis showed that total coliforms (TC) was significantly positively correlated with EnVs concentrations while no consistent significant correlations were observed between bacterial indices and viruses that precipitate acute gastroenteritis.Conclusions: Taken together, the findings provide insights into alternative viral indicators, suggesting that TC is a potentially promising candidate for assessment of EnVs contamination. However, it failed to predict the presence of HAdVs, HRVs, AstVs, and HuNoVs GΙΙ in surface water across the city of Tianjin. [ABSTRACT FROM AUTHOR]

Background: Intestinal parasitic infections (IPI) lead to significant morbidity and mortality in pediatric and adult populations worldwide. Intestinal parasitism during pregnancy is of interest as it may affect the health of pregnant women and their offspring. This study determined the prevalence of IPI in pregnant women living in substandard conditions in three urban districts of Bogotá, Colombia. Associations between prevalence and sociodemographic factors, housing, and living conditions were also evaluated.Methods: In a cross-sectional and community-based study, pregnant women were recruited from three districts of Bogotá. A total of 550 participants answered a questionnaire; 331 of these also provided stool samples, with 233 providing one and 98 providing two stool samples. Questionnaire responses were associated with the presence of intestinal parasites, which was determined using a standard combined microscopy technique including direct wet mount and formol-ether concentration. Results were verified by supplementary examination of 48 stool samples by quantitative polymerase chain reaction (qPCR).Results: Among pregnant women who lived in selected poor residential areas in Bogotá, the overall prevalence of intestinal parasitism was 41% with 9% polyparasitism. Pathogenic parasites were present in 1.2% of the 331 participants including Giardia lamblia and Ascaris lumbricoides. Higher prevalence was found for parasites with debated pathogenicity, including Blastocystis hominis (25%), Endolimax nana (15%), Entamoeba coli (8%), and Iodamoeba butschlii (2%). Entamoeba histolytica/dispar complex was also detected (1.5%). When comparing a subset of stool samples using the combined microscopy technique and qPCR, the latter detected a higher 58.3% overall IPI prevalence. Higher prevalence of infections by any intestinal parasite was found in participants who had never been dewormed (p = 0.01). Higher but not statistically significant associations were found between any parasite and women living with a partner, and intestinal polyparasitism and being from a minority group and not having a water sink.Conclusions: This first study of the prevalence of intestinal parasitism in Bogotá focused on pregnant women living in poverty, found a high prevalence of intestinal parasites of debated pathogenicity, and confirmed a low prevalence of pathogenic intestinal parasites. These results highlight the need for educational interventions to disrupt transmission routes for prevalent parasites. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are important regulatory factors of life activities, which are involved in the regulation of glucose, lipid and energy metabolisms, and closely associated with intestinal hormones, microbiotas and energy balance. BAs abnormalities easily lead to inflammation and metabolic diseases, in turn, the progress of diseases could influence characteristics of BAs. Therefore, accurate detection of BAs contents is of great significance to disease prevention, diagnosis and treatment. At present, the most widely used enzymatic method in clinical practice is applicable to the detection of total bile acid (TBA). In laboratory research, different types of BAs can be accurately separated and quantified by liquid chromatography-mass spectrometry (LC-MS). The metabolic profiling of BAs based on detection technologies can completely and accurately monitor their types and contents, playing a crucial role in disease prevention, diagnosis and treatment. We herein reviewed the main detection technologies of BAs and the application of metabolic profiling in related diseases in recent years. [ABSTRACT FROM AUTHOR]