RESUMO
During high-intensity (HI) exercise, metabolic acidosis significantly impairs exercise performance. Increasing the body's buffering capacity through training and exogenous intake of alkalizing supplements may improve high-intensity performance. Manipulating water and diet intake may influence the acid-base balance. The aim of this study was to determine the effects of mineral water rich in bicarbonate ions (STY) or placebo water (PLA) on circulating biomarkers and anaerobic performance and to verify whether alkalizing (ALK) or acidizing (ACI) diet would modulate these effects. Twenty-four athletes, assigned either to ALK (n = 12) or ACI (n = 12) diet for four weeks, completed a 1-min rowing Wingate Test in a double-blind and randomized trial after one week of daily hydration (1.5 to 2L/d) with either STY or PLA. Blood samples were taken before and after each test, and urine samples were collected each week. Chronic consumption of bicarbonate-rich water significantly impacted resting urinary pH irrespective of alkalizing or acidizing dietary intake. STY induced a significant increase in blood pH, lactate, and HCO3 - ion concentration post-exercise compared to PLA. Similar changes were observed when STY was associated with the ALK diet. In contrast, STY combined with the ACI diet only significantly affected urine pH and peak blood lactate compared to PLA (p < 0.05). No effect of bicarbonate-rich water was reported on anaerobic performance (p > 0.05). Our results suggest that consumption of bicarbonate-rich water alters acid-base balance during a warm-up and after HI exercise, could potentiate beneficial effects of an alkalizing diet on the acid-base balance after HI exercise, and reduces the acid load induced by an acidifying diet.
RESUMO
BACKGROUND: Folate is involved in multiple genetic, epigenetic, and metabolic processes, and inadequate folate intake has been associated with an increased risk of cancer. OBJECTIVE: We examined whether folate intake is differentially associated with colorectal cancer (CRC) risk according to somatic mutations in genes linked to CRC using targeted sequencing. DESIGN: Participants within 2 large CRC consortia with available information on dietary folate, supplemental folic acid, and total folate intake were included. Colorectal tumor samples from cases were sequenced for the presence of nonsilent mutations in 105 genes and 6 signaling pathways (IGF2/PI3K, MMR, RTK/RAS, TGF-ß, WNT, and TP53/ATM). Multinomial logistic regression models were analyzed comparing mutated/nonmutated CRC cases to controls to compute multivariable-adjusted odds ratios (ORs) with 95% confidence interval (CI). Heterogeneity of associations of mutated compared with nonmutated CRC cases was tested in case-only analyses using logistic regression. Analyses were performed separately in hypermutated and nonhypermutated tumors, because they exhibit different clinical behaviors. RESULTS: We included 4339 CRC cases (702 hypermutated tumors, 16.2%) and 11,767 controls. Total folate intake was inversely associated with CRC risk (OR = 0.93; 95% CI: 0.90, 0.96). Among hypermutated tumors, 12 genes (AXIN2, B2M, BCOR, CHD1, DOCK3, FBLN2, MAP3K21, POLD1, RYR1, TET2, UTP20, and ZNF521) showed nominal statistical significance (P < 0.05) for heterogeneity by mutation status, but none remained significant after multiple testing correction. Among these genetic subtypes, the associations between folate variables and CRC were mostly inverse or toward the null, except for tumors mutated for DOCK3 (supplemental folic acid), CHD1 (total folate), and ZNF521 (dietary folate) that showed positive associations. We did not observe differential associations in analyses among nonhypermutated tumors, or according to the signaling pathways. CONCLUSIONS: Folate intake was not differentially associated with CRC risk according to mutations in the genes explored. The nominally significant differential mutation effects observed in a few genes warrants further investigation.
RESUMO
This study aimed to investigate the ability of highly trained athletes to consistently perform at their highest level during a simulated three-day 400 m race and to examine the impact of an alkaline diet associated with chronic consumption of bicarbonate-rich water or placebo on their blood metabolic responses before and after the three races. Twenty-two highly trained athletes, divided into two groups-one with an alkalizing diet and placebo water (PLA) and the other with an alkalizing diet and bicarbonate-rich water (BIC)-performed a 400 m race for three consecutive days. Performance metrics, urine and blood samples assessing acid-base balance, and indirect markers of neuro-muscular fatigue were measured before and after each 400 m race. The evolution of the Potential Renal Acid Load (PRAL) index and urinary pH highlights the combination of an alkalizing diet and bicarbonate-rich hydration, modifying the acid-base state (p < 0.05). Athletes in the PLA group replicated the same level of performance during three consecutive daily races without an increase in fatigue-associated markers. Athletes experienced similar levels of metabolic perturbations during the three 400 m races, with improved lactate clearance 20 min after the third race compared to the first two (p < 0.05). This optimization of the buffering capacity through ecological alkaline nutrition and hydration allowed athletes in the BIC group to improve their performance during the third 400 m race (p < 0.01). This study highlights athletes' ability to replicate high-level performances over three consecutive days with the same extreme level of metabolic disturbances, and an alkaline diet combined with bicarbonate-rich water consumption appears to enhance performance in a 400 m race.
Assuntos
Equilíbrio Ácido-Base , Desempenho Atlético , Bicarbonatos , Humanos , Desempenho Atlético/fisiologia , Masculino , Adulto , Bicarbonatos/sangue , Atletas , Adulto Jovem , Concentração de Íons de Hidrogênio , Dieta/métodos , Ácido Láctico/sangue , Feminino , Fadiga Muscular/fisiologia , Corrida/fisiologia , Resistência Física/fisiologia , Biomarcadores/sangue , Biomarcadores/urinaRESUMO
BACKGROUND: Consumption of fibre, fruits and vegetables have been linked with lower colorectal cancer (CRC) risk. A genome-wide gene-environment (G × E) analysis was performed to test whether genetic variants modify these associations. METHODS: A pooled sample of 45 studies including up to 69,734 participants (cases: 29,896; controls: 39,838) of European ancestry were included. To identify G × E interactions, we used the traditional 1--degree-of-freedom (DF) G × E test and to improve power a 2-step procedure and a 3DF joint test that investigates the association between a genetic variant and dietary exposure, CRC risk and G × E interaction simultaneously. FINDINGS: The 3-DF joint test revealed two significant loci with p-value <5 × 10-8. Rs4730274 close to the SLC26A3 gene showed an association with fibre (p-value: 2.4 × 10-3) and G × fibre interaction with CRC (OR per quartile of fibre increase = 0.87, 0.80, and 0.75 for CC, TC, and TT genotype, respectively; G × E p-value: 1.8 × 10-7). Rs1620977 in the NEGR1 gene showed an association with fruit intake (p-value: 1.0 × 10-8) and G × fruit interaction with CRC (OR per quartile of fruit increase = 0.75, 0.65, and 0.56 for AA, AG, and GG genotype, respectively; G × E -p-value: 0.029). INTERPRETATION: We identified 2 loci associated with fibre and fruit intake that also modify the association of these dietary factors with CRC risk. Potential mechanisms include chronic inflammatory intestinal disorders, and gut function. However, further studies are needed for mechanistic validation and replication of findings. FUNDING: National Institutes of Health, National Cancer Institute. Full funding details for the individual consortia are provided in acknowledgments.
Assuntos
Neoplasias Colorretais , Fibras na Dieta , Frutas , Interação Gene-Ambiente , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Verduras , Humanos , Neoplasias Colorretais/genética , Neoplasias Colorretais/etiologia , Fibras na Dieta/administração & dosagem , Genótipo , Dieta , Masculino , Feminino , Fatores de RiscoRESUMO
The purpose of this study was to identify causes of quadriceps muscle weakness in facioscapulohumeral muscular dystrophy (FSHD). To this aim, we evaluated quadriceps muscle and fat volumes by magnetic resonance imaging and their relationships with muscle strength and oxidative stress markers in adult patients with FSHD (n = 32) and healthy controls (n = 7), and the effect of antioxidant supplementation in 20 of the 32 patients with FSHD (n = 10 supplementation and n = 10 placebo) (NCT01596803). Compared with healthy controls, the dominant quadriceps strength and quality (muscle strength per unit of muscle volume) were decreased in patients with FSHD. In addition, fat volume was increased, without changes in total muscle volume. Moreover, in patients with FSHD, the lower strength of the non-dominant quadriceps was associated with lower muscle quality compared with the dominant muscle. Antioxidant supplementation significantly changed muscle and fat volumes in the non-dominant quadriceps, and muscle quality in the dominant quadriceps. This was associated with improved muscle strength (both quadriceps) and antioxidant response. These findings suggest that quadriceps muscle strength decline may not be simply explained by atrophy and may be influenced also by the muscle intrinsic characteristics. As FSHD is associated with increased oxidative stress, supplementation might reduce oxidative stress and increase antioxidant defenses, promoting changes in muscle function.
Assuntos
Antioxidantes , Suplementos Nutricionais , Força Muscular , Distrofia Muscular Facioescapuloumeral , Estresse Oxidativo , Músculo Quadríceps , Humanos , Distrofia Muscular Facioescapuloumeral/tratamento farmacológico , Distrofia Muscular Facioescapuloumeral/fisiopatologia , Distrofia Muscular Facioescapuloumeral/metabolismo , Distrofia Muscular Facioescapuloumeral/dietoterapia , Distrofia Muscular Facioescapuloumeral/patologia , Estresse Oxidativo/efeitos dos fármacos , Antioxidantes/administração & dosagem , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Masculino , Feminino , Força Muscular/efeitos dos fármacos , Adulto , Pessoa de Meia-Idade , Músculo Quadríceps/metabolismo , Músculo Quadríceps/patologia , Músculo Quadríceps/fisiopatologia , Músculo Quadríceps/efeitos dos fármacos , Imageamento por Ressonância Magnética , Tecido Adiposo/metabolismo , Tecido Adiposo/efeitos dos fármacosRESUMO
Purpose: To highlight clinical and imaging features of 5 patients diagnosed with retinal vasculitis and cryoglobulins. Methods: This retrospective case series describes clinical and angiographic features of retinal vasculitis and serum cryoglobulins and is the most extensive series to our knowledge. Results: Five female patients were diagnosed with retinal vasculitis and serum cryoglobulins. The average age at time of cryoglobulin identification was 46 years (range, 28-72 years), although retinal vasculitis had been present for various durations. Fluorescein angiograms demonstrated large-vessel and small-vessel segmental leakage in 3 patients, only large-vessel segmental leakage in 1 patient, and only small-vessel segmental leakage in 1 patient. Treatment included topical steroids, intraocular steroid injections, oral corticosteroids, oral antimetabolites, and biologic therapy. At the time of this report, 4 of 5 patients had persistent angiographic leakage; however, none had retinal vascular occlusions. Conclusions: Various treatments were efficacious, although resolution was difficult. No patient experienced retinal vascular occlusions or other types of end-organ compromise.
RESUMO
BACKGROUND: Obesity has been positively associated with most molecular subtypes of colorectal cancer (CRC); however, the magnitude and the causality of these associations is uncertain. METHODS: We used Mendelian randomization (MR) to examine potential causal relationships between body size traits (body mass index [BMI], waist circumference, and body fat percentage) with risks of Jass classification types and individual subtypes of CRC (microsatellite instability [MSI] status, CpG island methylator phenotype [CIMP] status, BRAF and KRAS mutations). Summary data on tumour markers were obtained from two genetic consortia (CCFR, GECCO). FINDINGS: A 1-standard deviation (SD:5.1 kg/m2) increment in BMI levels was found to increase risks of Jass type 1MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype (odds ratio [OR]: 2.14, 95% confidence interval [CI]: 1.46, 3.13; p-value = 9 × 10-5) and Jass type 2non-MSI-high,CIMP-high,BRAF-mutated,KRAS-wildtype CRC (OR: 2.20, 95% CI: 1.26, 3.86; p-value = 0.005). The magnitude of these associations was stronger compared with Jass type 4non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-wildtype CRC (p-differences: 0.03 and 0.04, respectively). A 1-SD (SD:13.4 cm) increment in waist circumference increased risk of Jass type 3non-MSI-high,CIMP-low/negative,BRAF-wildtype,KRAS-mutated (OR 1.73, 95% CI: 1.34, 2.25; p-value = 9 × 10-5) that was stronger compared with Jass type 4 CRC (p-difference: 0.03). A higher body fat percentage (SD:8.5%) increased risk of Jass type 1 CRC (OR: 2.59, 95% CI: 1.49, 4.48; p-value = 0.001), which was greater than Jass type 4 CRC (p-difference: 0.03). INTERPRETATION: Body size was more strongly linked to the serrated (Jass types 1 and 2) and alternate (Jass type 3) pathways of colorectal carcinogenesis in comparison to the traditional pathway (Jass type 4). FUNDING: Cancer Research UK, National Institute for Health Research, Medical Research Council, National Institutes of Health, National Cancer Institute, American Institute for Cancer Research, Brigham and Women's Hospital, Prevent Cancer Foundation, Victorian Cancer Agency, Swedish Research Council, Swedish Cancer Society, Region Västerbotten, Knut and Alice Wallenberg Foundation, Lion's Cancer Research Foundation, Insamlingsstiftelsen, Umeå University. Full funding details are provided in acknowledgements.
Assuntos
Neoplasias Colorretais , Proteínas Proto-Oncogênicas B-raf , Humanos , Feminino , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Análise da Randomização Mendeliana , Metilação de DNA , Proteínas Proto-Oncogênicas p21(ras)/genética , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Instabilidade de Microssatélites , Mutação , Fenótipo , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Neoplasias Colorretais/metabolismo , Tamanho Corporal , Ilhas de CpGRESUMO
BACKGROUND: The genotoxin colibactin causes a tumor single-base substitution (SBS) mutational signature, SBS88. It is unknown whether epidemiologic factors' association with colorectal cancer risk and survival differs by SBS88. METHODS: Within the Genetic Epidemiology of Colorectal Cancer Consortium and Colon Cancer Family Registry, we measured SBS88 in 4,308 microsatellite stable/microsatellite instability low tumors. Associations of epidemiologic factors with colorectal cancer risk by SBS88 were assessed using multinomial regression (N = 4,308 cases, 14,192 controls; cohort-only cases N = 1,911), and with colorectal cancer-specific survival using Cox proportional hazards regression (N = 3,465 cases). RESULTS: 392 (9%) tumors were SBS88 positive. Among all cases, the highest quartile of fruit intake was associated with lower risk of SBS88-positive colorectal cancer than SBS88-negative colorectal cancer [odds ratio (OR) = 0.53, 95% confidence interval (CI) 0.37-0.76; OR = 0.75, 95% CI 0.66-0.85, respectively, Pheterogeneity = 0.047]. Among cohort studies, associations of body mass index (BMI), alcohol, and fruit intake with colorectal cancer risk differed by SBS88. BMI ≥30 kg/m2 was associated with worse colorectal cancer-specific survival among those SBS88-positive [hazard ratio (HR) = 3.40, 95% CI 1.47-7.84], but not among those SBS88-negative (HR = 0.97, 95% CI 0.78-1.21, Pheterogeneity = 0.066). CONCLUSIONS: Most epidemiologic factors did not differ by SBS88 for colorectal cancer risk or survival. Higher BMI may be associated with worse colorectal cancer-specific survival among those SBS88-positive; however, validation is needed in samples with whole-genome or whole-exome sequencing available. IMPACT: This study highlights the importance of identification of tumor phenotypes related to colorectal cancer and understanding potential heterogeneity for risk and survival.
Assuntos
Neoplasias Colorretais , Instabilidade de Microssatélites , Peptídeos , Policetídeos , Humanos , Dano ao DNA , Neoplasias Colorretais/epidemiologia , Neoplasias Colorretais/genética , Fatores Epidemiológicos , Fatores de RiscoRESUMO
OBJECTIVES: The purpose of this study was to report patterns of scapular fractures and define them with a contemporary methodology. METHODS: . DESIGN: Retrospective study, 2015-2021. SETTING: Single, academic, Level 1 trauma center. PATIENT SELECTION CRITERIA: Consecutive patients ≥18 years, presenting with unilateral scapula fracture, with thin-slice (≤0.5-mm) bilateral computed tomography (CT) scans of the entirety of both the injured and uninjured scapulae. OUTCOME MEASURES AND COMPARISONS: Thin-slice (0.5-mm) CT scans of injured and normal scapulae were obtained to create three-dimensional (3D) virtual models. 3D modeling software (Stryker Orthopedics Modeling and Analytics, Stryker Trauma GmbH, Kiel, Germany aka SOMA) was used to create a 3D map of fracture location and frequency. Fracture zones were delineated using anatomic landmarks to characterize fracture patterns. RESULTS: Eighty-seven patients were identified with 75 (86%) extra-articular and 12 (14%) intra-articular fractures. The dominant fracture pattern emanated from the superior lateral border (zone E) to an area inferior to the spinomedial angle (zone B) and was present in 80% of extra-articular fractures. A second-most common fracture line propagated from the primary (most-common) line toward the inferior medial scapular border with a frequency of 36%. Bare zones (with 1 or no fractures present) were identified in 4 unique areas. Furthermore, intra-articular fractures were found to be heterogenous. CONCLUSIONS: The 3D fracture map created in this study confirmed that extra-articular scapular fractures occur in certain patterns with a relatively high frequency. Results provide greater insight into scapular fracture locations and may help to study prognosis of injury and improve treatment strategy including operative approaches and surgical tactics.
Assuntos
Fraturas Ósseas , Fraturas Intra-Articulares , Fraturas do Ombro , Humanos , Fraturas Intra-Articulares/cirurgia , Estudos Retrospectivos , Escápula/diagnóstico por imagem , Escápula/lesões , Fraturas Ósseas/diagnóstico por imagem , Fraturas Ósseas/cirurgia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: High red meat and/or processed meat consumption are established colorectal cancer risk factors. We conducted a genome-wide gene-environment (GxE) interaction analysis to identify genetic variants that may modify these associations. METHODS: A pooled sample of 29,842 colorectal cancer cases and 39,635 controls of European ancestry from 27 studies were included. Quantiles for red meat and processed meat intake were constructed from harmonized questionnaire data. Genotyping arrays were imputed to the Haplotype Reference Consortium. Two-step EDGE and joint tests of GxE interaction were utilized in our genome-wide scan. RESULTS: Meta-analyses confirmed positive associations between increased consumption of red meat and processed meat with colorectal cancer risk [per quartile red meat OR = 1.30; 95% confidence interval (CI) = 1.21-1.41; processed meat OR = 1.40; 95% CI = 1.20-1.63]. Two significant genome-wide GxE interactions for red meat consumption were found. Joint GxE tests revealed the rs4871179 SNP in chromosome 8 (downstream of HAS2); greater than median of consumption ORs = 1.38 (95% CI = 1.29-1.46), 1.20 (95% CI = 1.12-1.27), and 1.07 (95% CI = 0.95-1.19) for CC, CG, and GG, respectively. The two-step EDGE method identified the rs35352860 SNP in chromosome 18 (SMAD7 intron); greater than median of consumption ORs = 1.18 (95% CI = 1.11-1.24), 1.35 (95% CI = 1.26-1.44), and 1.46 (95% CI = 1.26-1.69) for CC, CT, and TT, respectively. CONCLUSIONS: We propose two novel biomarkers that support the role of meat consumption with an increased risk of colorectal cancer. IMPACT: The reported GxE interactions may explain the increased risk of colorectal cancer in certain population subgroups.
Assuntos
Neoplasias Colorretais , Carne Vermelha , Humanos , Interação Gene-Ambiente , Carne Vermelha/efeitos adversos , Carne/efeitos adversos , Fatores de Risco , Neoplasias Colorretais/genéticaRESUMO
BACKGROUND: The correction and control of chronic hyperglycemia are the management goals of patients living with diabetes. Chronic hyperglycemia is the main factor inducing diabetes-related complications. However, in certain situations, the rapid and intense correction of chronic hyperglycemia can paradoxically favor the onset of microvascular complications. CASE SUMMARY: In this case report, we describe the case of a 25-year-old woman living with type 1 diabetes since the age of 9 years. Her diabetes was chronic and unstable but without complications. During an unplanned pregnancy, her diabetes was intensely managed with the rapid correction of her hyperglycemia. However, over the following 2 years, she developed numerous degenerative microvascular complications: Charcot neuroarthropathy with multiple joint involvement, severe proliferative diabetic retinopathy, gastroparesis, bladder voiding disorders, and end-stage renal failure requiring hemodialysis. CONCLUSION: In the literature to date, the occurrence of multiple microvascular complications following the rapid correction of chronic hyperglycemia has been rarely described in the same individual.
RESUMO
BACKGROUND: Microarray patches (MAPs) deliver vaccines to the epidermis and the upper dermis, where abundant immune cells reside. There are several potential benefits to using MAPs, including reduced sharps risk, thermostability, no need for reconstitution, tolerability and self-administration. We aimed to explore and evaluate the immunogenicity, safety, usability and acceptability of MAPs for vaccination. METHODS: We searched CINAHL, Cochrane Library, Ovid Embase, Ovid MEDLINE and Web of Science from inception to January 2023. Eligibility criteria included all research studies in any language, which examined microarrays or microneedles intended or used for vaccination and explored immunogenicity, safety, usability or acceptability in their findings. Two reviewers conducted title and abstract screening, full-text reviewing and data extraction. RESULTS: Twenty-two studies were included (quantitative=15, qualitative=2 and mixed methods=5). The risk of bias was mostly low, with two studies at high risk of bias. Four clinical trials were included, three using influenza antigens and one with Japanese encephalitis delivered by MAP. A meta-analysis indicated similar or higher immunogenicity in influenza MAPs compared with needle and syringe (N&S) (standardised mean difference=10.80, 95% CI: 3.51 to 18.08, p<0.00001). There were no significant differences in immune cell function between MAPs and N&S. No serious adverse events were reported in MAPs. Erythema was more common after MAP application than N&S but was brief and well tolerated. Lower pain scores were usually reported after MAP application than N&S. Most studies found MAPs easy to use and highly acceptable among healthcare professionals, laypeople and parents. CONCLUSION: MAPs for vaccination were safe and well tolerated and evoked similar or enhanced immunogenicity than N&S, but further research is needed. Vaccine uptake may be increased using MAPs due to less pain, enhanced thermostability, layperson and self-administration. MAPs could benefit at-risk groups and low and middle-income countries. PROSPERO REGISTRATION NUMBER: CRD42022323026.
Assuntos
Influenza Humana , Vacinas , Humanos , Vacinação , Dor/etiologia , Dor/prevenção & controleRESUMO
During mitosis, microtubules in the spindle turn over continuously. At spindle poles, where microtubule minus ends are concentrated, microtubule nucleation and depolymerization, the latter required for poleward microtubule flux, happen side by side. How these seemingly antagonistic processes of nucleation and depolymerization are coordinated is not understood. Here, we reconstitute this coordination in vitro combining different pole-localized activities. We find that the spindle pole-localized kinesin-13 KIF2A is a microtubule minus-end depolymerase, in contrast to its paralog MCAK. Due to its asymmetric activity, KIF2A still allows microtubule nucleation from the γ-tubulin ring complex (γTuRC), which serves as a protective cap shielding the minus end against KIF2A binding. Efficient γTuRC uncapping requires the combined action of KIF2A and a microtubule severing enzyme, leading to treadmilling of the uncapped microtubule driven by KIF2A. Together, these results provide insight into the molecular mechanisms by which a minimal protein module coordinates microtubule nucleation and depolymerization at spindle poles consistent with their role in poleward microtubule flux.
Assuntos
Cinesinas , Centro Organizador dos Microtúbulos , Cinesinas/genética , Microtúbulos , Mitose , Polos do Fuso , HumanosRESUMO
The PIK3CA-related overgrowth spectrum (PROS) encompasses various conditions caused by mosaic activating PIK3CA variants. PIK3CA somatic variants are also involved in various cancer types. Some generalized overgrowth syndromes are associated with an increased risk of Wilms tumor (WT). In PROS, abdominal ultrasound surveillance has been advocated to detect WT. We aimed to determine the risk of embryonic and other types of tumors in patients with PROS in order to evaluate surveillance relevance. We searched the clinical charts from 267 PROS patients for the diagnosis of cancer, and reviewed the medical literature for the risk of cancer. In our cohort, six patients developed a cancer (2.2%), and Kaplan Meier analyses estimated cumulative probabilities of cancer occurrence at 45 years of age was 5.6% (95% CI = 1.35%-21.8%). The presence of the PIK3CA variant was only confirmed in two out of four tumor samples. In the literature and our cohort, six cases of Wilms tumor/nephrogenic rests (0.12%) and four cases of other cancers have been reported out of 483 proven PIK3CA patients, in particular the p.(His1047Leu/Arg) variant. The risk of WT in PROS being lower than 5%, this is insufficient evidence to recommend routine abdominal imaging. Long-term follow-up studies are needed to evaluate the risk of other cancer types, as well as the relationship with the extent of tissue mosaicism and the presence or not of the variant in the tumor samples.
Assuntos
Neoplasias Renais , Tumor de Wilms , Humanos , Mutação , Detecção Precoce de Câncer , Transtornos do Crescimento/diagnóstico , Tumor de Wilms/diagnóstico , Tumor de Wilms/epidemiologia , Tumor de Wilms/genética , Classe I de Fosfatidilinositol 3-Quinases/genéticaRESUMO
BACKGROUND: Chromosome 15q24 microdeletion is a rare genetic disorder, and the skin manifestations are poorly documented. OBJECTIVES: In this cross-sectional observational study using social media (Facebook), we investigated the prevalence of atopic dermatitis in 15q24 microdeletion syndrome. MATERIALS & METHODS: Parents and caregivers of a child with the syndrome were asked to participate using a validated self-reporting questionnaire. RESULTS: In total, 60 participants completed the questionnaire. The prevalence of atopic dermatitis was 35% among patients with chromosome 15q24 deletion. Few patients received treatment according to international guidelines. CONCLUSION: We describe the largest cohort of patients with 15q24 microdeletion syndrome, revealing a high prevalence of atopic dermatitis. Patients with 15q24 microdeletion syndrome should undergo dermatological evaluation for screening and management of atopic dermatitis. Approaching individuals via social media is a successful strategy, resulting in good information which may be used to counsel families.
Assuntos
Dermatite Atópica , Mídias Sociais , Criança , Humanos , Dermatite Atópica/genética , Estudos Transversais , Deleção Cromossômica , Doenças RarasRESUMO
BACKGROUND: There is an urgent need to identify biomarkers for advanced adenoma, an important precursor of colorectal cancer (CRC). We aimed to determine alterations in ileal juice bile acids associated with colorectal advanced adenoma. METHODS: We quantified a comprehensive panel of primary and secondary bile acids and their conjugates using an ultraperformance liquid chromatography triple-quadrupole mass spectrometric assay in ileal juice collected at colonoscopy from 46 study subjects (i.e., 14 biopsy-confirmed advanced adenomas and 32 controls free of adenoma or cancer). Using analysis of covariance (ANCOVA), we examined the differences in bile acid concentrations by disease status, adjusting for age, sex, body mass index, smoking status and type 2 diabetes. RESULTS: The concentrations of hyodeoxycholic acid (HCA) species in ileal juice of the advanced adenoma patients (geometric mean = 4501.9 nM) were significantly higher than those of controls (geometric mean = 1292.3 nM, p = 0.001). The relative abundance of ursodeoxycholic acid (UDCA) in total bile acids was significantly reduced in cases than controls (0.73% in cases vs. 1.33% in controls; p = 0.046). No significant difference between cases and controls was observed for concentrations of total or specific primary bile acids (i.e., cholic acid (CA), chenodeoxycholic acid (CDCA) and their glycine- and taurine-conjugates) and total and specific major secondary bile acids (i.e., deoxycholic acid and lithocholic acid). CONCLUSIONS: Colorectal advanced adenoma was associated with altered bile acids in ileal juice. The HCA species may promote the development of colorectal advanced adenoma, whereas gut microbiota responsible for the conversion of CDCA to UDCA may protect against it. Our findings have important implications for the use of bile acids as biomarkers in early detection of colorectal cancer.
Assuntos
Adenoma , Neoplasias Colorretais , Diabetes Mellitus Tipo 2 , Humanos , Ácidos e Sais Biliares , Ácido Ursodesoxicólico , Neoplasias Colorretais/diagnóstico , Ácido QuenodesoxicólicoRESUMO
Queen conch (Aliger gigas) are large gastropod molluscs harvested for their meat, shells, and pearls and as they are generally easy to collect by hand, they are vulnerable to overfishing. In The Bahamas, fishers often clean (or "knock") their catch and dispose of the shells away from collection sites, forming midden heaps or "graveyards". Although queen conch are motile and found throughout shallow water habitats, live animals are rarely observed in the vicinity of middens, giving rise to a common belief that conch actively avoid graveyards, possibly by moving offshore. Here, we experimentally evaluated avoidance behaviours of queen conch to chemical (tissue homogenate) and visual (shells) cues indicative of harvesting activity using replicated aggregations of six size-selected small (< 14 cm shell length) and large (> 14 cm) conch at Eleuthera Island. Large conch were consistently more likely to move, and to move farther, than small conch, independent of treatment. Small conch, however, demonstrated greater occurrence of movement in response to chemical cues vs seawater controls, while conch of both sizes demonstrated equivocal responses to visual cues. Collectively, these observations suggest that more economically desirable large conch may be less vulnerable to capture during successive harvest events than smaller juveniles due to their greater propensity to move, and that chemical cues consistent with damage-released alarm cues may play a greater role in eliciting avoidance behaviour than the visual cues typically associated with queen conch graveyards. DATA AVAILABILITY: Data and R code are archived and freely available at Open Science Framework (https://osf.io/x8t7p/; DOI: 10.17605/OSF.IO/X8T7P).
Assuntos
Conservação dos Recursos Naturais , Gastrópodes , Animais , Cemitérios , Sinais (Psicologia) , PesqueirosRESUMO
Diabetes complications can be related to the long duration of the disease or chronic hyperglycemia. The follow-up of diabetic patients is based on the control of chronic hyperglycemia, although this correction, if obtained rapidly in people living with severe chronic hyperglycemia, can paradoxically interfere with the disease or even induce complications. We reviewed the literature describing the impact of the rapid and intense treatment of hyperglycemia on diabetic complications. The literature review showed that worsening complications occurred significantly in diabetic microangiopathy with the onset of specific neuropathy induced by the correction of diabetes. The results for macroangiopathy were somewhat mixed with the intensive and rapid correction of chronic hyperglycemia having a neutral impact on stroke and myocardial infarction but a significant increase in cardiovascular mortality. The management of diabetes has now entered a new era with new therapeutic molecules, such as gliflozin for patients living with type 2 diabetes, or hybrid insulin delivery systems for patients with insulin-treated diabetes. Our manuscript provides evidence in support of these personalized and progressive algorithms for the control of chronic hyperglycemia.