An efficient inducible model for the control of gene expression in renin cells.

Fate mapping and genetic manipulation of renin cells have relied on either non-inducible Cre lines that can introduce developmental effects of gene deletion or BAC transgene-based inducible models that may be prone to spurious and/or ectopic gene expression. To circumvent these problems, we generated an inducible mouse model in which CreERT2 is under the control of the endogenous Akr1b7 gene, an independent marker of renin cells that is expressed in a few extrarenal tissues. We confirmed the proper expression of Cre using Akr1b7CreERT2/+;R26RmTmG/+ mice in which Akr1b7+/renin+ cells become GFP+ upon tamoxifen administration. In embryos and neonates, GFP was found in Juxtaglomerular cells, along the arterioles, and in the mesangium, and in adults, GFP was present mainly in Juxtaglomerular cells. In mice treated with captopril and a low salt diet to induce recruitment of renin cells, GFP extended along the afferent arterioles and in the mesangium. We generated Akr1b7CreERT2/+;Ren1cFl/-;R26RmTmG/+ mice to conditionally delete renin in adult mice and found a marked reduction in kidney renin mRNA and protein, and mean arterial pressure in mutant animals. When subjected to a homeostatic threat, mutant mice were unable to recruit renin+ cells. Most importantly, these mice developed concentric vascular hypertrophy ruling out potential developmental effects on the vasculature due to the lack of renin. We conclude that Akr1b7CreERT2 mice constitute an excellent model for the fate mapping of renin cells and for the spatial and temporal control of gene expression in renin cells.

Discovery in space of ethanolamine, the simplest phospholipid head group.

Cell membranes are a key element of life because they keep the genetic material and metabolic machinery together. All present cell membranes are made of phospholipids, yet the nature of the first membranes and the origin of phospholipids are still under debate. We report here the presence of ethanolamine in space, [Formula: see text]OH, which forms the hydrophilic head of the simplest and second-most-abundant phospholipid in membranes. The molecular column density of ethanolamine in interstellar space is N = (1.51[Formula: see text]0.07)[Formula: see text], implying a molecular abundance with respect to [Formula: see text] of [Formula: see text] Previous studies reported its presence in meteoritic material, but they suggested that it is synthesized in the meteorite itself by decomposition of amino acids. However, we find that the proportion of the molecule with respect to water in the interstellar medium is similar to the one found in the meteorite ([Formula: see text]). These results indicate that ethanolamine forms efficiently in space and, if delivered onto early Earth, could have contributed to the assembling and early evolution of primitive membranes.

Prevalence of low bone mineral density (T-score ≤ - 2.5) in the whole spectrum of chronic kidney disease: a systematic review and meta-analysis.

The prevalence of low bone mineral density (LBMD) in people with chronic kidney disease (CKD) remains unknown. We identified a high prevalence of LBMD in CKD population. Thus, public health strategies should include efforts to prevent, early detect, and manage LBMD in CKD patients, especially in patients undergoing kidney replacement therapy. Mineral and bone disorders are common among patients with CKD, which affects bone mineral density. We conducted a systematic review and meta-analysis to estimate the prevalence of low bone mineral density (LBMD) in adults with CKD. We searched MEDLINE, EMBASE, Web of Science, CINAHL, and LILACS databases from inception to February 2021. Observational studies that reported the prevalence of LBMD in adults with CKD stages 3a-5D were included. The LBMD was defined according to the World Health Organization criterion (T-score ≤ - 2.5). Random-effect model meta-analyses were used to estimate the pooled prevalence of LBMD. Meta-regressions and subgroup analyses were conducted for stages of CKD, dialysis modality, gender, bone sites and morphology, and geographical region. This study was registered in PROSPERO, number CRD42020211077. One-hundred and fifty-three studies with 78,092 patients were included. The pooled global prevalence of LBMD in CKD was 24.5% (95% CI, 21.3 - 27.8%). Subgroup analyses indicated a higher prevalence of LBMD in dialysis patients (30%, 95% CI 25 - 35%) compared with non-dialysis CKD patients (12%, 95% CI 8 - 16%), cortical bone sites (28%, 95% CI 23 - 35%) relative to trabecular sites (19%, 95% CI 14 - 24%), while similar estimates in the European and the Asiatic continents (26%, 95% CI 21 - 30% vs 25%, 95% CI 21 - 29). The prevalence of LBMD in CKD patients is high, particularly in those undergoing dialysis and in cortical bone sites. Therefore, efforts to early diagnosis and management strategies should be implemented in clinical routine for an epidemiological control of LBMD in CKD patients.

Milk kefir alters fecal microbiota impacting gut and brain health in mice.

Kefir is a fermented beverage made of a symbiotic microbial community that stands out for health benefits. Although its microbial profile is still little explored, its effects on modulation of gut microbiota and production of short-chain fatty acids (SCFAs) seems to act by improving brain health. This work aimed to analyze the microbiota profile of milk kefir and its effect on metabolism, oxidative stress, and in the microbiota-gut-brain axis in a murine model. The experimental design was carried out using C57BL-6 mice (n = 20) subdivided into groups that received 0.1 mL water or 0.1 mL (10% w/v) kefir. The kefir proceeded to maturation for 48 h, and then it was orally administered, via gavage, to the animals for 4 weeks. Physicochemical, microbiological, antioxidant analyzes, and microbial profiling of milk kefir beverage were performed as well as growth parameters, food intake, serum markers, oxidative stress, antioxidant enzymes, SCFAs, and metabarcoding were analyzed in the mice. Milk kefir had 76.64 ± 0.42% of free radical scavenging and the microbiota composed primarily by the genus Comamonas. Moreover, kefir increased catalase and superoxide dismutase (colon), and SCFAs in feces (butyrate), and in the brain (butyrate and propionate). Kefir reduced triglycerides, uric acid, and affected the microbiome of animals increasing fecal butyrate-producing bacteria (Lachnospiraceae and Lachnoclostridium). Our results on the brain and fecal SCFAs and the antioxidant effect found were associated with the change in the gut microbiota caused by kefir, which indicates that kefir positively influences the gut-microbiota-brain axis and contributes to the preservation of gut and brain health. KEY POINTS: • Milk kefir modulates fecal microbiota and SCFA production in brain and colon. • Kefir treatment increases the abundance of SCFA-producing bacteria. • Milk kefir increases antioxidant enzymes and influences the metabolism of mice.

Implementing telemedicine in urogynecology: A feasibility study.

INTRODUCTION AND HYPOTHESIS: Telemedicine has been recommended for the management of urogynecological conditions during the coronavirus (COVID 19) pandemic. This study aimed to evaluate the feasibility of telemedicine for urogynecology at a Brazilian public hospital. METHODS: A descriptive observational study was performed at a urogynecology outpatient clinic. The primary outcome was the desire to continue with telemedicine. Secondary outcomes were appointment resolvability, technical aspects of the appointment, and patient satisfaction. The participants had in-person appointments that were canceled because of the COVID-19 pandemic. We collected data on sociodemographic characteristics and clinical and technical aspects of the appointments. The participants responded to satisfaction questionnaires 7-15 days post-procedure. The categorical variables were evaluated based on absolute and relative frequency. The continuous variables were described as the mean and standard deviation. A chi-square test was performed to determine the association between variables. RESULTS: In total, 225 patients had appointments canceled due to the COVID-19 pandemic, of which 171 were eligible for the study. Telemedicine appointments were agreed upon by 48% of the participants and 85.5% responded to the satisfaction survey. We found that 57.7% of the participants desired to continue with telemedicine. The appointment resolvability rate was 76.1%, 63.4% of the appointments met the technical criteria, and the satisfaction rate was 93%. The only variable associated with the desire to continue telemedicine was overall patient satisfaction (p=0.02). CONCLUSIONS: Telemedicine in urogynecology is feasible and can be implemented in the studied population. However, actions are essential to adequately support patient preference and improve the acceptance of telemedicine.

Chikungunya virus infection in the southernmost state of Brazil was characterised by self-limited transmission (2017-2019) and a larger 2021 outbreak.

BACKGROUND: Chikungunya is a mosquito-borne virus that has been causing large outbreaks in the Americas since 2014. In Brazil, Asian-Caribbean (AC) and East-Central-South-African (ECSA) genotypes have been detected and lead to large outbreaks in several Brazilian states. In Rio Grande do Sul (RS), the southernmost state of Brazil, the first cases were reported in 2016. OBJECTIVES AND METHODS: We employed genome sequencing and epidemiological investigation to characterise the Chikungunya fever (CHIKF) burden in RS between 2017-2021. FINDINGS: We detected an increasing CHIKF burden linked to travel associated introductions and communitary transmission of distinct lineages of the ECSA genotype during this period. MAIN CONCLUSIONS: Until 2020, CHIKV introductions were most travel associated and transmission was limited. Then, in 2021, the largest outbreak occurred in the state associated with the introduction of a new ECSA lineage. CHIKV outbreaks are likely to occur in the near future due to abundant competent vectors and a susceptible population, exposing more than 11 million inhabitants to an increasing infection risk.

Tetracycline Removal through the Synergy of Catalysis and Photocatalysis by Novel NaYF4:Yb,Tm@TiO2-Acetylacetone Hybrid Core-Shell Structures.

Novel hybrid core-shell structures, in which up-converting (UC) NaYF4:Yb,Tm core converts near-infrared (NIR) to visible (Vis) light via multiphoton up-conversion processes, while anatase TiO2-acetylacetonate (TiO2-Acac) shell ensures absorption of the Vis light through direct injection of excited electrons from the highest-occupied-molecular-orbital (HOMO) of Acac into the TiO2 conduction band (CB), were successfully synthesized by a two-step wet chemical route. Synthesized NaYF4:Yb,Tm@TiO2-Acac powders were characterized by X-ray powder diffraction, thermogravimetric analysis, scanning and transmission electron microscopy, diffuse-reflectance spectroscopy, Fourier transform infrared spectroscopy, and photoluminescence emission measurement. Tetracycline, as a model drug, was used to investigate the photocatalytic efficiencies of the core-shell structures under irradiation of reduced power Vis and NIR spectra. It was shown that the removal of tetracycline is accompanied by the formation of intermediates, which formed immediately after bringing the drug into contact with the novel hybrid core-shell structures. As a result, ~80% of tetracycline is removed from the solution after 6 h.

Serum uric acid is independently associated with metabolic syndrome and systemic hypertension in women from northeast Brazil.

Hyperuricemia (HU) has been associated with cardiovascular risk and metabolic syndrome (MS) worldwide. However, inconsistencies about this relation are still reported, and it is not clear whether hyperuricemia is an independent risk factor for MS. The aim of this study was to determine hyperuricemia associations with systemic hypertension and MS in women from northeast Brazil. The study included 301 women. Hyperuricemia was considered for serum uric acid (SUA) ≥6 mg/dL. Insulin resistance (IR) was measured by TyG index (TyG ≥ 4.55). Fisher test and Multivariate logistic regression analyses estimated the association between hyperuricemia (or SUA level) and systemic hypertension and MS. Hyperuricemia association with systemic hypertension was independent of age, body-mass index (BMI), smoking and alcoholism (OR: OR: 4.6050; p = .000256), and MS components (OR: 4.1296; IC95% 1.8330_9.3033; p = .000621). Hyperuricemia increased risk of systemic hypertension by 4,6 -fold. SUA level was associated with MS, independently of other classic component factors of the syndrome (OR:1.34, p = .0129). Hyperuricemia and high SUA levels were associated with MS and systemic hypertension. Effect of hyperuricemia in systemic hypertension is independent of age, BMI, lifestyle, and MS factors. SUA levels are independently associated with MS.

Alterations in Kidney Structures Caused by Age Vary According to Sex and Dehydration Condition.

Aging is a complex biological process, resulting in gradual and progressive decline in structure and function in many organ systems. Our objective is to determine if structural changes produced by aging vary with sex in a stressful situation such as dehydration. The expression of Slc12a3 mRNA in the renal cortex, α-smooth muscle actin (α-SMA), and fibronectin was evaluated in male and female rats, aged 3 and 18 months, submitted and not submitted to water deprivation (WD) for 48 h, respectively. When comparing ages, 18-month-old males showed a lower expression of Slc12a3 mRNA than 3-month-old males, and control and WD 18-month-old male and female rats exhibited a higher expression of α-SMA than the respective 3-month-old rats. Fibronectin was higher in both control and WD 18-month-old males than the respective 3-month-old males. In females, only the control 18-month-old rats showed higher fibronectin than the control 3-month-old rats. When we compared sex, control and WD 3-month-old female rats had a lower expression of Slc12a3 mRNA than the respective males. The WD 18-month-old male rats presented a higher expression of fibronectin and α-SMA than the WD 18-month-old female rats. When we compared hydric conditions, the WD 18-month-old males displayed a lower relative expression of Slc12a3 mRNA and higher α-SMA expression than the control 18-month-old males. Aging, sex, and dehydration lead to alterations in kidney structure.

Calcitriol Reduces the Inflammation, Endothelial Damage and Oxidative Stress in AKI Caused by Cisplatin.

Cisplatin treatment is one of the most commonly used treatments for patients with cancer. However, thirty percent of patients treated with cisplatin develop acute kidney injury (AKI). Several studies have demonstrated the effect of bioactive vitamin D or calcitriol on the inflammatory process and endothelial injury, essential events that contribute to changes in renal function and structure caused by cisplatin (CP). This study explored the effects of calcitriol administration on proximal tubular injury, oxidative stress, inflammation and vascular injury observed in CP-induced AKI. Male Wistar Hannover rats were pretreated with calcitriol (6 ng/day) or vehicle (0.9% NaCl). The treatment started two weeks before i.p. administration of CP or saline and was maintained for another five days after the injections. On the fifth day after the injections, urine, plasma and renal tissue samples were collected to evaluate renal function and structure. The animals of the CP group had increased plasma levels of creatinine and of fractional sodium excretion and decreased glomerular filtration rates. These changes were associated with intense tubular injury, endothelial damage, reductions in antioxidant enzymes and an inflammatory process observed in the renal outer medulla of the animals from this group. These changes were attenuated by treatment with calcitriol, which reduced the inflammation and increased the expression of vascular regeneration markers and antioxidant enzymes.

A Genome-wide Association Study Identifies SERPINB10, CRLF3, STX7, LAMP3, IFNG-AS1, and KRT80 As Risk Loci Contributing to Cutaneous Leishmaniasis in Brazil.

BACKGROUND: Our goal was to identify genetic risk factors for cutaneous leishmaniasis (CL) caused by Leishmania braziliensis. METHODS: Genotyping 2066 CL cases and 2046 controls using Illumina HumanCoreExomeBeadChips provided data for 4 498 586 imputed single-nucleotide variants (SNVs). A genome-wide association study (GWAS) using linear mixed models took account of genetic diversity/ethnicity/admixture. Post-GWAS positional, expression quantitative trait locus (eQTL) and chromatin interaction mapping was performed in Functional Mapping and Annotation (FUMA). Transcriptional data were compared between lesions and normal skin, and cytokines measured using flow cytometry and Bioplex assay. RESULTS: Positional mapping identified 32 genomic loci associated with CL, none achieving genome-wide significance (P < 5 × 10-8). Lead SNVs at 23 loci occurred at protein coding or noncoding RNA genes, 15 with eQTLs for functionally relevant cells/tissues and/or showing differential expression in lesions. Of these, the 6 most plausible genetic risk loci were SERPINB10 (Pimputed_1000G = 2.67 × 10-6), CRLF3 (Pimputed_1000G = 5.12 × 10-6), STX7 (Pimputed_1000G = 6.06 × 10-6), KRT80 (Pimputed_1000G = 6.58 × 10-6), LAMP3 (Pimputed_1000G = 6.54 × 10-6), and IFNG-AS1 (Pimputed_1000G = 1.32 × 10-5). LAMP3 (Padjusted = 9.25 × 10-12; +6-fold), STX7 (Padjusted = 7.62 × 10-3; +1.3-fold), and CRLF3 (Padjusted = 9.19 × 10-9; +1.97-fold) were expressed more highly in CL biopsies compared to normal skin; KRT80 (Padjusted = 3.07 × 10-8; -3-fold) was lower. Multiple cis-eQTLs across SERPINB10 mapped to chromatin interaction regions of transcriptional/enhancer activity in neutrophils, monocytes, B cells, and hematopoietic stem cells. Those at IFNG-AS1 mapped to transcriptional/enhancer regions in T, natural killer, and B cells. The percentage of peripheral blood CD3+ T cells making antigen-specific interferon-γ differed significantly by IFNG-AS1 genotype. CONCLUSIONS: This first GWAS for CL identified multiple genetic risk loci including a novel lead to understanding CL pathogenesis through regulation of interferon-γ by IFNG antisense RNA 1.

Role of the renin-angiotensin system in kidney development and programming of adult blood pressure.

Adverse events during fetal life such as insufficient protein intake or elevated transfer of glucocorticoid to the fetus may impact cardiovascular and metabolic health later in adult life and are associated with increased incidence of type 2 diabetes, ischemic heart disease and hypertension. Several adverse factors converge and suppress the fetal renin-angiotensin-aldosterone system (RAAS). The aim of this review is to summarize data on the significance of RAAS for kidney development and adult hypertension. Genetic inactivation of RAAS in rodents at any step from angiotensinogen to angiotensin II (ANGII) type 1 receptor (AT1) receptors or pharmacologic inhibition leads to complex developmental injury to the kidneys that has also been observed in human case reports. Deletion of the 'protective' arm of RAAS, angiotensin converting enzyme (ACE) 2 (ACE-2) and G-protein coupled receptor for Angiotensin 1-7 (Mas) receptor does not reproduce the AT1 phenotype. The changes comprise fewer glomeruli, thinner cortex, dilated tubules, thicker arterioles and arteries, lack of vascular bundles, papillary atrophy, shorter capillary length and volume in cortex and medulla. Altered activity of systemic and local regulators of fetal-perinatal RAAS such as vitamin D and cyclooxygenase (COX)/prostaglandins are associated with similar injuries. ANGII-AT1 interaction drives podocyte and epithelial cell formation of vascular growth factors, notably vascular endothelial growth factor (VEGF) and angiopoietins (Angpts), which support late stages of glomerular and cortical capillary growth and medullary vascular bundle formation and patterning. RAAS-induced injury is associated with lower glomerular filtration rate (GFR), lower renal plasma flow, kidney fibrosis, up-regulation of sodium transporters, impaired sodium excretion and salt-sensitive hypertension. The renal component and salt sensitivity of programmed hypertension may impact dietary counseling and choice of pharmacological intervention to treat hypertension.

FLI1 gene influences lesion size and skin test may predict therapeutic response in cutaneous leishmaniasis.

Genes associated with wound healing have been shown to be risk factors for cutaneous leishmaniasis (CL) which is caused by Leishmania braziliensis. In this study, we examined whether the genes previously associated with CL influenced the clinical outcome. Patients were genotyped and retrospectively classified as responders, who were cured with a single course of pentavalent antimony (Sbv), or as refractories, who did not respond to Sbv. Patients characterised as responders showed a stronger response to the leishmanin skin test (LST) when compared to the refractory subjects (p = 0.0003). Furthermore, we observed an association between the FLI1 CC genotype and an increased size of ulcers (p = 0.0170). We suggest that the leishmanin skin test may be a predictive tool for therapeutic outcome and reinforce FLI1 as a potential influencer of susceptibility and lesion size in CL.

Influence of urban forest on traffic air pollution and children respiratory health.

This study aimed to assess the air quality, the prevalence of child respiratory morbidity, and the association between them, in urban areas where concentrations of pollutants are expected to be below national limits. The monitoring of PM10, NO2 and O3 was performed in five schools, during 9 months. Information about respiratory diseases and associated symptoms were collected from each student using a questionnaire based on the International Study of Asthma and Allergies in Childhood. The PM10 and NO2 concentrations were higher at points closer to roads and avenues with intense vehicle flow and lower at the point closer to a park, with dense vegetation. All sampling points exceeded the annual limit established by WHO for PM10. Some maximum PM10 concentrations recorded close to the road was six times higher than the international limit. In total, 340 answered questionnaires were collected (68% response rate). Respiratory symptoms such as wheezing, sneezing, running nose, tearing, and itchy eyes had positive and strong correlation to the primary pollutants (0.70 to 0.87), but the frequency of some symptoms was lower close to the urban forest. Therefore, our results confirm the importance of creating and maintaining green areas in urban space, considering all ecosystem services provided by them, especially the improvement of air quality. In addition, a continuous program to monitor and control atmospheric pollution is required in mid-sized counties located nearby important roads, with growing fleets of vehicles.

Previous Exercise Effects in Cisplatin-Induced Renal Lesions in Rats.

BACKGROUND/AIMS: Physical training has beneficial effects on endothelial function and can influence the regeneration of the endothelial cell. We investigated the effect of physical training on cisplatin (CP)-induced acute kidney injury and assessed the impact of training on endothelial structure and function, and on the inflammatory processes in rats. METHODS: We injected male Wistar rats subjected to previous physical training in treadmill running (trained, TR) or not (sedentary, SED) with CP (5 mg/kg) (TR+CP and SED+CP groups, respectively). Five days after the injections, blood and urine samples were collected to evaluate renal function and kidneys were harvested for morphological, immunohistochemical, enzyme-linked immunosorbent assay, and analysis of nitric oxide (NO) levels. RESULTS: Rats treated with CP showed increased levels of plasma creatinine and sodium and potassium fractional excretion. These alterations were associated with increase in tubulointerstitial lesions and macrophage number, reduction of endothelial cells, and increased VEGF, vimentin, and α-smooth muscle actin expression in the outer renal medulla in the SED+CP group. We also found increased levels of renal IL-1ß and increased excretion of monocyte chemoattractant protein-1 and transforming growth factor-ß compared with controls. These changes were milder in trained rats, associated with increased levels of renal tissue NO, and increased expression of p-eNOS and stromal cell-derived factor-1α (a chemokine involved in kidney repair) in the kidneys of CP-injected trained rats. CONCLUSIONS: The protective effect of previous training in CP-treated rats was associated with reduced endothelial cell lesions and increased renal production of NO in trained rats.

Polymorphisms in genes TLR1, 2 and 4 are associated with differential cytokine and chemokine serum production in patients with leprosy.

BACKGROUND: Leprosy or hansen's disease is a spectral disease whose clinical forms mostly depends on host's immune and genetic factors. Different Toll-like receptors (TLR) variants have been described associated with leprosy, but with some lack of replication across different populations. OBJECTIVES: To evaluate the role of polymorphisms in genes TLR1, TLR2 and TLR4 and susceptibility to leprosy in a genetic case control study; to verify the association between genotypes of these markers and the immunological profile in the serum of patients with leprosy. METHODS: Pre-designed TaqMan® assays were used to genotype markers at TLR1 (rs4833095, rs5743551), TLR2 (rs7656411, rs3804099) and TLR4 (rs1927914, rs1927911). A panel of cytokines and chemokines was accessed by enzime-linked immunosorbent assay (ELISA) test in the serum of a subgroup of patients with and without leprosy reactions. FINDINGS: Our results show an association between the T allele of rs3804099 at the TLR2 gene and increased risk for leprosy per se [Odds ratio (OR) = 1.296, p = 0,022]. In addition, evaluating the association between different genotypes of the TLR1, 2 and 4 markers and cytokine/chemokine serological levels, IL-17 appears as an immunological marker regulated by the polymorphism of the three TLR genes evaluated, whereas different TLR1 genotypes were associated with differential production of IL-12p40 and MCP-1(CCL2). Furthermore, other relevant serum markers such as CXCL-10 and IL-6 seemed to be regulated by TLR2 variants and IL-1ß was related to TLR4 genotypes. MAIN CONCLUSIONS: All together our data points that the tested TLR markers may have a regulatory role in the immunity against Mycobacterium leprae, by driving the host's production of key cytokines and chemokines involved in the pathogenesis of this disease.

Proteomics of Secretory-Stage and Maturation-Stage Enamel of Genetically Distinct Mice.

The mechanisms by which excessive ingestion of fluoride (F) during amelogenesis leads to dental fluorosis (DF) are still not precisely known. Inbred strains of mice vary in their susceptibility to develop DF, and therefore permit the investigation of underlying molecular events influencing DF severity. We employed a proteomic approach to characterize and evaluate changes in protein expression from secretory-stage and maturation-stage enamel in 2 strains of mice with different susceptibilities to DF (A/J, i.e. 'susceptible' and 129P3/J, i.e. 'resistant'). Weanling male and female susceptible and resistant mice fed a low-F diet were divided into 2 F-water treatment groups. They received water containing 0 (control) or 50 mg F/l for 6 weeks. Plasma and incisor enamel was analyzed for F content. For proteomic analysis, the enamel proteins extracted for each group were separated by 2-dimensional electrophoresis and subsequently characterized by liquid-chromatography electrospray-ionization quadrupole time-of-flight mass spectrometry. F data were analyzed by 2-way ANOVA and Bonferroni's test (p < 0.05). Resistant mice had significantly higher plasma and enamel F concentrations when compared with susceptible mice in the F-treated groups. The proteomic results for mice treated with 0 mg F/l revealed that during the secretory stage, resistant mice had a higher abundance of proteins than their susceptible counterparts, but this was reversed during the maturation stage. Treatment with F greatly increased the number of protein spots detected in both stages. Many proteins not previously described in enamel (e.g. type 1 collagen) as well as some uncharacterized proteins were identified. Our findings reveal new insights regarding amelogenesis and how genetic background and F affect this process.

Screening for celiac disease in 1st degree relatives: a 10-year follow-up study.

BACKGROUND: Although it is known that first degree relatives of celiac patients have an increased risk for celiac disease few studies are available on its incidence. We investigated the incidence of serologic conversion and of new cases of celiac disease among first degree relatives with negative results at a first screening. METHODS: From a total of 634 first degree relatives of 186 biopsy-proven celiac disease patients diagnosed between October 2000 and October 2010, 450 subjects agreed to participate in the study (Group I), and underwent serologic screening. Between January 2010 and October 2012, out of the initial group of 450, 205 previously sero-negative subjects consented to participate in a second stage of the study and undergo new serologic testing (Group II). All serologically positive individuals of both groups (I and II) were genotyped for celiac disease-predisposing alleles (HLA-DQ2/DQ8). RESULTS: 19 subjects (4.2%) out of the 450 subjects of Group I disclosed positive serologic results, presence of DQ2 and/or DQ8 alleles and celiac disease-compatible mucosal abnormalities. The 205 previously negative first degree relatives from Group II that underwent new serologic testing disclosed eight sero-converted subjects. Mucosal abnormalities in five of these patients confirmed the diagnosis of celiac disease. During the 10-year period of the study the incidence of sero-conversion was 8/205 and the incidence of biopsy-proven celiac disease cases was 5/205. CONCLUSIONS: Our data are coincident with other works on this subject and confirm once again that relatives of celiac patients, especially first degree relatives are at high risk of developing celiac disease. In view of the relatively low incidence further studies are needed to try to establish a useful and cost-effective algorithm for follow-up of relatives of celiac patients.

Host genetic factors in American cutaneous leishmaniasis: a critical appraisal of studies conducted in an endemic area of Brazil.

American cutaneous leishmaniasis (ACL) is a vector-transmitted infectious disease with an estimated 1.5 million new cases per year. In Brazil, ACL represents a significant public health problem, with approximately 30,000 new reported cases annually, representing an incidence of 18.5 cases per 100,000 inhabitants. Corte de Pedra is in a region endemic for ACL in the state of Bahia (BA), northeastern Brazil, with 500-1,300 patients treated annually. Over the last decade, population and family-based candidate gene studies were conducted in Corte de Pedra, founded on previous knowledge from studies on mice and humans. Notwithstanding limitations related to sample size and power, these studies contribute important genetic biomarkers that identify novel pathways of disease pathogenesis and possible new therapeutic targets. The present paper is a narrative review about ACL immunogenetics in BA, highlighting in particular the interacting roles of the wound healing gene FLI1 with interleukin-6 and genes SMAD2 and SMAD3 of the transforming growth factor beta signalling pathway. This research highlights the need for well-powered genetic and functional studies on Leishmania braziliensis infection as essential to define and validate the role of host genes in determining resistance/susceptibility regarding this disease.

Improvements in cardiorespiratory fitness, muscle strength and body composition to modest weight loss are similar in those with adult- versus childhood-onset obesity.

Adults who have had obesity from childhood are at greater risk of obesity-related comorbidities compared to those who only develop obesity in adulthood. The main way of mitigating these risks in obesity is with weight loss, which has been shown to positively affect the cardiorespiratory fitness (CRF) and body composition of adults. However, it is unclear whether the response of these outcomes to weight loss may be influenced by age of obesity onset. The objective of our study was to investigate how age of obesity onset mitigates the responsiveness of CRF, muscle strength and body composition to modest weight loss. Measurements were conducted at baseline and 12 weeks. In total, 37 participants (childhood-onset = 19, adult-onset = 18) lost 3.7% ± 0.4% through aerobic exercise and diet. The YMCA cycle ergometer test (YMCA) and the 20-m shuttle run test (20MSR) were used to estimate CRF (mL kg-1 min-1 ) and a handgrip dynamometer was used to estimate muscle strength. Total body composition was assessed by dual-energy x-ray absorptiometry (DEXA). Overall, CRF and body composition improved (time effect: p < 0.05) after 12 weeks. There was no group-by-time interaction for YMCA, 20MSR, muscle strength and body composition variables. Therefore, the present study suggests that individuals with childhood-onset obesity and adult-onset obesity can improve their CRF and body composition similarly after mild weight loss.