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1.
Eur J Hum Genet ; 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38605124

RESUMO

Persistent congenital hyperinsulinism (HI) is a rare genetically heterogeneous condition characterised by dysregulated insulin secretion leading to life-threatening hypoglycaemia. For up to 50% of affected individuals screening of the known HI genes does not identify a disease-causing variant. Large deletions have previously been used to identify novel regulatory regions causing HI. Here, we used genome sequencing to search for novel large (>1 Mb) deletions in 180 probands with HI of unknown cause and replicated our findings in a large cohort of 883 genetically unsolved individuals with HI using off-target copy number variant calling from targeted gene panels. We identified overlapping heterozygous deletions in five individuals (range 3-8 Mb) spanning chromosome 20p11.2. The pancreatic beta-cell transcription factor gene, FOXA2, a known cause of HI was deleted in two of the five individuals. In the remaining three, we found a minimal deleted region of 2.4 Mb adjacent to FOXA2 that encompasses multiple non-coding regulatory elements that are in conformational contact with FOXA2. Our data suggests that the deletions in these three children may cause disease through the dysregulation of FOXA2 expression. These findings provide new insights into the regulation of FOXA2 in the beta-cell and confirm an aetiological role for chromosome 20p11.2 deletions in syndromic HI.

2.
Artigo em Inglês | MEDLINE | ID: mdl-38480070

RESUMO

OBJECTIVE: The purpose of this study was to identify whether age is associated with mucocele recurrence after excision. STUDY DESIGN: This retrospective cohort study consisted of 492 patients who underwent oral mucocele excision at Boston Children's Hospital from 2010 to 2022. Fisher's exact tests were used to assess the association between age and mucocele recurrence. An adjusted logistic regression model was run to evaluate the effect of age on mucocele recurrence while controlling for confounders. A P value < .05 was considered significant. RESULTS: Mucocele recurrence was observed in 24 cases (4.9%). There was a significant association between age and mucocele recurrence (2.2% for <7 years vs. 2.9% for 7 to <13 years vs. 9.2% for 13 to <18 years vs. 8.9% for >18 years; P = .005). Sex; history of behavioral disorders; mucocele size, duration, and location; suture technique; and type of anesthesia were not significantly associated with recurrence (P > .135). An adjusted logistic regression model verified a significant association between age and mucocele recurrence (odds ratio, 1.053; 95% confidence interval, 1.019-1.088; P = .035). CONCLUSIONS: Mucocele recurrence occurs infrequently in patients younger than 7 years and is most prevalent in the teenage to young adult patient population. For every year increase in age, the odds of mucocele recurrence increase by 5.3%.

3.
Plast Reconstr Surg ; 2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38546729

RESUMO

BACKGROUND: There is evidence that patient-specific plate fixation for Le Fort I osteotomies (LFI) is more stable than traditional plates. The purpose of this study was to evaluate stability of LFI in patients with cleft lip and palate (CLP) and determine stability differences between patient-specific and stock plates. METHODS: Consecutive patients with CLP who underwent isolated LFI by one surgeon (BLP) between 2016 and 2021 were included. The predictor variable was type of plate used for fixation (patient-specific or stock). The outcome variable was magnitude of relapse in the vertical (Nasion-A point) and horizontal planes (Basion-A point) at one year post LFI using 3-dimensional cone beam computed tomography. Statistical analysis included Independent Samples T-test, Mann-Whitney U, Fisher's exact and Chi-square tests. P<0.05 was significant. RESULTS: The sample included 63 subjects; 23 (36.5%) in the patient-specific group and 40 (63.5%) in the stock group. Groups were comparable by sex, race, age at operation, cleft type, presence of pharyngeal flap and magnitude of horizontal movement (P>0.136, all). Subjects who underwent patient-specific plate fixation were less likely to have ≥1mm change at one year in the horizontal (4.3% vs. 50.0%, p<.001) and vertical planes (4.3% vs. 65.0%, P<.001) compared to stock plates. For patients who had >10mm horizontal advancement, the patient-specific plates had significantly less relapse (patient-specific 0.105mm ± 0.317mm vs. stock 1.888mm ± 1.125mm vs, P=.003). CONCLUSIONS: Patient-specific plate fixation of LFI is more stable and demonstrates less relapse after one year than stock plates. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

4.
BMJ Open ; 14(2): e077156, 2024 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-38307535

RESUMO

INTRODUCTION: Coexisting multiple health conditions is common among older people, a population that is increasing globally. The potential for polypharmacy, adverse events, drug interactions and development of additional health conditions complicates prescribing decisions for these patients. Artificial intelligence (AI)-generated decision-making tools may help guide clinical decisions in the context of multiple health conditions, by determining which of the multiple medication options is best. This study aims to explore the perceptions of healthcare professionals (HCPs) and patients on the use of AI in the management of multiple health conditions. METHODS AND ANALYSIS: A qualitative study will be conducted using semistructured interviews. Adults (≥18 years) with multiple health conditions living in the West Midlands of England and HCPs with experience in caring for patients with multiple health conditions will be eligible and purposively sampled. Patients will be identified from Clinical Practice Research Datalink (CPRD) Aurum; CPRD will contact general practitioners who will in turn, send a letter to patients inviting them to take part. Eligible HCPs will be recruited through British HCP bodies and known contacts. Up to 30 patients and 30 HCPs will be recruited, until data saturation is achieved. Interviews will be in-person or virtual, audio recorded and transcribed verbatim. The topic guide is designed to explore participants' attitudes towards AI-informed clinical decision-making to augment clinician-directed decision-making, the perceived advantages and disadvantages of both methods and attitudes towards risk management. Case vignettes comprising a common decision pathway for patients with multiple health conditions will be presented during each interview to invite participants' opinions on how their experiences compare. Data will be analysed thematically using the Framework Method. ETHICS AND DISSEMINATION: This study has been approved by the National Health Service Research Ethics Committee (Reference: 22/SC/0210). Written informed consent or verbal consent will be obtained prior to each interview. The findings from this study will be disseminated through peer-reviewed publications, conferences and lay summaries.


Assuntos
Inteligência Artificial , Medicina Estatal , Adulto , Humanos , Idoso , Estudos Transversais , Multimorbidade , Pesquisa Qualitativa , Polimedicação
5.
J Oral Maxillofac Surg ; 82(3): 270-278, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38043584

RESUMO

BACKGROUND: Anesthesia provider experience impacts nausea and vomiting in other surgical specialties but its influence within orthognathic surgery remains unclear. PURPOSE: The study purpose was to evaluate whether anesthesiologist experience with orthognathic surgery impacts postoperative outcomes, including nausea, emesis, narcotic use, and perioperative adverse events, for patients undergoing orthognathic surgery. STUDY DESIGN, SETTING, SAMPLE: This is a retrospective cohort study of subjects aged 12 to 35 years old who underwent orthognathic surgery, including Le Fort 1 osteotomy ± bilateral sagittal split osteotomy, at Boston Children's Hospital from August 2018 to January 2022. Subjects were excluded if they had incomplete medical records, a syndromic diagnosis, or a hospital stay of greater than 2 days. PREDICTOR VARIABLE: The predictor variable was attending anesthesia provider experience with orthognathic surgery. Providers were classified as experienced or inexperienced, with experienced providers defined as having anesthetized ≥10 orthognathic operations during the study period. MAIN OUTCOME VARIABLES: The primary outcome variable was postoperative nausea. Secondary outcome variables were emesis, narcotic use in the hospital, and perioperative adverse events within 30 days of their operation. COVARIATES: Study covariates included age, sex, race, comorbidities (body mass index, history of psychiatric illness, cleft lip and/or palate, chronic pain, postoperative nausea/vomiting, gastrointestinal conditions), enhanced recovery after surgery protocol enrollment, and intraoperative factors (operation performed, anesthesia/procedure times, estimated blood loss, intravenous fluid and narcotic administration, and anesthesiologist's years in practice). ANALYSES: χ2 and unpaired t-tests were used to compare primary predictor and covariates against outcome variables. A P-value <.05 was considered significant. RESULTS: There were 118 subjects included in the study after 4 were excluded (51.7% female, mean age 19.1 ± 3.30 years). There were 71 operations performed by 5 experienced anesthesiologists (mean cases/provider 15.4 ± 5.95) and 47 cases by 22 different inexperienced providers (mean cases/provider 1.91 ± 1.16). The nausea rate was 52.1% for experienced providers and 53.2% for inexperienced providers (P = .909). There were no statistically significant associations between anesthesiologist experience and any outcome variable (P > .341). CONCLUSIONS AND RELEVANCE: Anesthesia providers' experience with orthognathic surgery did not significantly influence postoperative nausea, emesis, narcotic use, or perioperative adverse events.


Assuntos
Anestesia Dentária , Fenda Labial , Fissura Palatina , Cirurgia Ortognática , Procedimentos Cirúrgicos Ortognáticos , Criança , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Masculino , Procedimentos Cirúrgicos Ortognáticos/efeitos adversos , Procedimentos Cirúrgicos Ortognáticos/métodos , Anestesiologistas , Fenda Labial/cirurgia , Estudos Retrospectivos , Náusea e Vômito Pós-Operatórios/etiologia , Fissura Palatina/cirurgia , Osteotomia de Le Fort/efeitos adversos , Osteotomia de Le Fort/métodos , Entorpecentes
6.
J Ophthalmol ; 2023: 7961623, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37946723

RESUMO

Purpose: Previous studies have demonstrated an association between melatonin status and both refractive error and axial length in young adult myopes. This study aimed to determine if this relationship extends to a younger adolescent cohort. Methods: Healthy children aged 12-15 years provided morning saliva samples before attending Ulster University (55°N) for cycloplegic autorefraction and axial length measures. Participants completed questionnaires describing recent sleep habits and physical activity. Salivary melatonin was quantified using high-performance liquid chromatography-tandem mass spectrometry. Data collection for all participants occurred over a 1-week period (April 2021). Results: Seventy participants aged 14.3 (95% CI: 14.2-14.5) years were categorised by spherical equivalent refraction [SER] (range: -5.38DS to +1.88DS) into two groups; myopic SER ≤ -0.50DS (n = 22) or nonmyopic -0.50DS < SER ≤ +2.00DS (n = 48). Median morning salivary melatonin levels were 4.52 pg/ml (95% CI: 2.60-6.02) and 4.89 pg/ml (95% CI: 3.18-5.66) for myopic and nonmyopic subjects, respectively, and did not differ significantly between refractive groups (P = 0.91). Melatonin levels were not significantly correlated with SER, axial length, sleep, or activity scores (Spearman's rank, all P > 0.39). Higher levels of physical activity were associated with higher sleep quality (Spearman's rank, ρ = -0.28, P = 0.02). Conclusion: The present study found no significant relationship between morning salivary melatonin levels and refractive error or axial length in young adolescents. This contrasts with outcomes from a previous study of adults with comparable methodology, season of data collection, and geographical location. Prospective studies are needed to understand the discrepancies between adult and childhood findings and evaluate whether melatonin levels in childhood are indicative of an increased risk for future onset of myopia and/or faster axial growth trajectories and myopia progression in established myopes. Future work should opt for a comprehensive dim-light melatonin onset protocol to determine circadian phase.

7.
Nat Genet ; 55(12): 2075-2081, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37973953

RESUMO

Identifying genes linked to extreme phenotypes in humans has the potential to highlight biological processes not shared with all other mammals. Here, we report the identification of homozygous loss-of-function variants in the primate-specific gene ZNF808 as a cause of pancreatic agenesis. ZNF808 is a member of the KRAB zinc finger protein family, a large and rapidly evolving group of epigenetic silencers which target transposable elements. We show that loss of ZNF808 in vitro results in aberrant activation of regulatory potential contained in the primate-specific transposable elements it represses during early pancreas development. This leads to inappropriate specification of cell fate with induction of genes associated with liver identity. Our results highlight the essential role of ZNF808 in pancreatic development in humans and the contribution of primate-specific regions of the human genome to congenital developmental disease.


Assuntos
Anormalidades Congênitas , Elementos de DNA Transponíveis , Proteínas de Ligação a DNA , Pâncreas , Animais , Humanos , Diferenciação Celular , Genoma Humano , Primatas/anormalidades , Primatas/genética , Proteínas de Ligação a DNA/genética , Anormalidades Congênitas/genética , Pâncreas/anormalidades
8.
Front Endocrinol (Lausanne) ; 14: 1231043, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38027197

RESUMO

Congenital hyperinsulinism (CHI) is a condition characterised by severe and recurrent hypoglycaemia in infants and young children caused by inappropriate insulin over-secretion. CHI is of heterogeneous aetiology with a significant genetic component and is often unresponsive to standard medical therapy options. The treatment of CHI can be multifaceted and complex, requiring multidisciplinary input. It is important to manage hypoglycaemia in CHI promptly as the risk of long-term neurodisability arising from neuroglycopaenia is high. The UK CHI consensus on the practice and management of CHI was developed to optimise and harmonise clinical management of patients in centres specialising in CHI as well as in non-specialist centres engaged in collaborative, networked models of care. Using current best practice and a consensus approach, it provides guidance and practical advice in the domains of diagnosis, clinical assessment and treatment to mitigate hypoglycaemia risk and improve long term outcomes for health and well-being.


Assuntos
Hiperinsulinismo Congênito , Criança , Lactente , Humanos , Pré-Escolar , Consenso , Hiperinsulinismo Congênito/diagnóstico , Hiperinsulinismo Congênito/genética , Hiperinsulinismo Congênito/terapia , Pancreatectomia , Reino Unido
9.
R Soc Open Sci ; 10(10): 231428, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37885981

RESUMO

In species with sex-specific signalling traits that appear to be ornamental (i.e. are conspicuous and with no obvious natural selection benefit), the ornamented sex typically initiates courtship and is most active in courtship. Here, we report for the first time courtship displays in the extremely sexually dimorphic, female-ornamented wide-bodied pipefish (Stigmatopora nigra), revealing unexpected behaviours. Females use their sex-specific ornament during courtship displays, as expected, but rarely in female-female interactions. Surprisingly, males initiated 61% of reciprocated courtship bouts and chased females in 17% of the bouts. This chasing behaviour could be a form of male harassment or be indicative of female disinterest in ardent males, either of which was unexpected to be found in this female-ornamented species. Our results highlight the need to study the details of species' behaviours in considering the potential roles of sexual selection and sexual conflict in shaping sexual dimorphism.

10.
Commun Med (Lond) ; 3(1): 136, 2023 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-37794142

RESUMO

BACKGROUND: Monogenic diabetes presents opportunities for precision medicine but is underdiagnosed. This review systematically assessed the evidence for (1) clinical criteria and (2) methods for genetic testing for monogenic diabetes, summarized resources for (3) considering a gene or (4) variant as causal for monogenic diabetes, provided expert recommendations for (5) reporting of results; and reviewed (6) next steps after monogenic diabetes diagnosis and (7) challenges in precision medicine field. METHODS: Pubmed and Embase databases were searched (1990-2022) using inclusion/exclusion criteria for studies that sequenced one or more monogenic diabetes genes in at least 100 probands (Question 1), evaluated a non-obsolete genetic testing method to diagnose monogenic diabetes (Question 2). The risk of bias was assessed using the revised QUADAS-2 tool. Existing guidelines were summarized for questions 3-5, and review of studies for questions 6-7, supplemented by expert recommendations. Results were summarized in tables and informed recommendations for clinical practice. RESULTS: There are 100, 32, 36, and 14 studies included for questions 1, 2, 6, and 7 respectively. On this basis, four recommendations for who to test and five on how to test for monogenic diabetes are provided. Existing guidelines for variant curation and gene-disease validity curation are summarized. Reporting by gene names is recommended as an alternative to the term MODY. Key steps after making a genetic diagnosis and major gaps in our current knowledge are highlighted. CONCLUSIONS: We provide a synthesis of current evidence and expert opinion on how to use precision diagnostics to identify individuals with monogenic diabetes.


Some diabetes types, called monogenic diabetes, are caused by changes in a single gene. It is important to know who has this kind of diabetes because treatment can differ from that of other types of diabetes. Some treatments also work better than others for specific types, and some people can for example change from insulin injections to tablets. In addition, relatives can be offered a test to see if they are at risk. Genetic testing is needed to diagnose monogenic diabetes but is expensive, so it's not possible to test every person with diabetes for it. We evaluated published research on who should be tested and what test to use. Based on this, we provide recommendations for doctors and health care providers on how to implement genetic testing for monogenic diabetes.

11.
J Diabetes Investig ; 14(12): 1378-1382, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37602910

RESUMO

The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), are thought to be the main drivers of insulin secretion in individuals with sulfonylurea (SU)-treated KCNJ11 permanent neonatal diabetes. The aim of this study was to assess for the first time the incretin hormone response to carbohydrate and protein/fat in adults with sulfonylurea-treated KCNJ11 permanent neonatal diabetes compared with that of controls without diabetes. Participants were given a breakfast high in carbohydrate and an isocaloric breakfast high in protein/fat on two different mornings. Incremental area under the curve and total area under the curve (0-240 minutes) for total GLP-1 and GIP were compared between groups, using non-parametric statistical methods. Post-meal GLP-1 and GIP secretion were similar in cases and controls, suggesting this process is adenosine triphosphate-sensitive potassium channel-independent. Future research will investigate whether treatments targeting the incretin pathway are effective in individuals with KCNJ11 permanent neonatal diabetes who do not have good glycemic control on sulfonylurea alone.


Assuntos
Diabetes Mellitus Tipo 2 , Diabetes Mellitus , Recém-Nascido , Adulto , Humanos , Incretinas/uso terapêutico , Glucagon/metabolismo , Insulina/metabolismo , Glicemia/metabolismo , Polipeptídeo Inibidor Gástrico , Peptídeo 1 Semelhante ao Glucagon , Diabetes Mellitus Tipo 2/metabolismo
12.
Diabetes ; 72(11): 1729-1734, 2023 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-37639628

RESUMO

ONECUT1 (also known as HNF6) is a transcription factor involved in pancreatic development and ß-cell function. Recently, biallelic variants in ONECUT1 were reported as a cause of neonatal diabetes mellitus (NDM) in two subjects, and missense monoallelic variants were associated with type 2 diabetes and possibly maturity-onset diabetes of the young (MODY). Here we examine the role of ONECUT1 variants in NDM, MODY, and type 2 diabetes in large international cohorts of subjects with monogenic diabetes and >400,000 subjects from UK Biobank. We identified a biallelic frameshift ONECUT1 variant as the cause of NDM in one individual. However, we found no enrichment of missense or null ONECUT1 variants among 484 individuals clinically suspected of MODY, in whom all known genes had been excluded. Finally, using a rare variant burden test in the UK Biobank European cohort, we identified a significant association between heterozygous ONECUT1 null variants and type 2 diabetes (P = 0.006) but did not find an association between missense variants and type 2 diabetes. Our results confirm biallelic ONECUT1 variants as a cause of NDM and highlight monoallelic null variants as a risk factor for type 2 diabetes. These findings confirm the critical role of ONECUT1 in human ß-cell function.

13.
Diabetologia ; 66(11): 1997-2006, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37653058

RESUMO

AIMS/HYPOTHESIS: In pregnancies where the mother has glucokinase-MODY (GCK-MODY), fetal growth is determined by fetal genotype. When the fetus inherits a maternal pathogenic GCK variant, normal fetal growth is anticipated, and insulin treatment of maternal hyperglycaemia is not recommended. At present, fetal genotype is estimated from measurement of fetal abdominal circumference on ultrasound. Non-invasive prenatal testing of fetal GCK genotype (NIPT-GCK) using cell-free DNA in maternal blood has recently been developed. We aimed to compare the diagnostic accuracy of NIPT-GCK with that of ultrasound, and determine the feasibility of using NIPT-GCK to guide pregnancy management. METHODS: We studied an international cohort of pregnant women with hyperglycaemia due to GCK-MODY. We compared the diagnostic accuracy of NIPT-GCK with that of measurement of fetal abdominal circumference at 28 weeks' gestation (n=38) using a directly genotyped offspring sample as the reference standard. In a feasibility study, we assessed the time to result given to clinicians in 43 consecutive pregnancies affected by GCK-MODY between July 2019 and September 2021. RESULTS: In terms of diagnostic accuracy, NIPT-GCK was more sensitive and specific than ultrasound in predicting fetal genotype (sensitivity 100% and specificity 96% for NIPT-GCK vs sensitivity 53% and specificity 61% for fetal abdominal circumference 75th percentile). In terms of feasibility, a valid NIPT-GCK fetal genotype (≥95% probability) was reported in all 38 pregnancies with an amenable variant and repeated samples when needed. The median time to report was 5 weeks (IQR 3-8 weeks). For the 25 samples received before 20 weeks' gestation, results were reported at a median gestational age of 20 weeks (IQR 18-24), with 23/25 (92%) reported before 28 weeks. CONCLUSIONS/INTERPRETATION: Non-invasive prenatal testing of fetal genotype in GCK-MODY pregnancies is highly accurate and is capable of providing a result before the last trimester for most patients. This means that non-invasive prenatal testing of fetal genotype is the optimal approach to management of GCK-MODY pregnancies.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Gravidez , Humanos , Feminino , Lactente , Glucoquinase/genética , Estudos de Viabilidade , Medicina de Precisão , Diabetes Mellitus Tipo 2/genética , Hiperglicemia/genética , Mutação
14.
Horm Res Paediatr ; 2023 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-37454648

RESUMO

Hyperinsulinism (HI) due to dysregulation of pancreatic beta-cell insulin secretion is the most common and most severe cause of persistent hypoglycemia in infants and children. In the 65 years since HI in children was first described, there has been a dramatic advancement in the diagnostic tools available, including new genetic techniques and novel radiologic imaging for focal HI, however; there have been almost no new therapeutic modalities since the development of diazoxide. Recent advances in neonatal research and genetics have improved our understanding of the pathophysiology of both transient and persistent forms of neonatal hyperinsulinism. Rapid turnaround of genetic test results combined with advanced radiologic imaging can permit identification and localization of surgically-curable focal lesions in a large proportion of children with congenital forms of HI, but are only available in certain centers in 'developed' countries. Diazoxide, the only drug currently approved for treating HI, was recently designated as an "essential medicine" by the World Health Organization but has been approved in only 16% of Latin American countries and remains unavailable in many under-developed areas of the world. Novel treatments for HI are emerging, but they await completion of safety and efficacy trials before being considered for clinical use. This international consensus statement on diagnosis and management of HI was developed in order to assist specialists, general pediatricians, and neonatologists in early recognition and treatment of HI with the ultimate aim of reducing the prevalence of brain injury caused by hypoglycemia. A previous statement on diagnosis and management of HI in Japan was published in 2017. The current document provides an updated guideline for management of infants and children with HI and includes potential accommodations for less-developed regions of the world where resources may be limited.

15.
medRxiv ; 2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37131594

RESUMO

Monogenic forms of diabetes present opportunities for precision medicine as identification of the underlying genetic cause has implications for treatment and prognosis. However, genetic testing remains inconsistent across countries and health providers, often resulting in both missed diagnosis and misclassification of diabetes type. One of the barriers to deploying genetic testing is uncertainty over whom to test as the clinical features for monogenic diabetes overlap with those for both type 1 and type 2 diabetes. In this review, we perform a systematic evaluation of the evidence for the clinical and biochemical criteria used to guide selection of individuals with diabetes for genetic testing and review the evidence for the optimal methods for variant detection in genes involved in monogenic diabetes. In parallel we revisit the current clinical guidelines for genetic testing for monogenic diabetes and provide expert opinion on the interpretation and reporting of genetic tests. We provide a series of recommendations for the field informed by our systematic review, synthesizing evidence, and expert opinion. Finally, we identify major challenges for the field and highlight areas for future research and investment to support wider implementation of precision diagnostics for monogenic diabetes.

16.
Cleft Palate Craniofac J ; : 10556656231175337, 2023 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-37160755

RESUMO

Evaluate periodontal bone support of maxillary central incisors (MCI) in patients with bilateral complete cleft lip and palate (BCCLP). Determine if syndromic diagnosis, age at time of alveolar bone graft (ABG), presence of maxillary lateral incisor (MLI), history of dentofacial orthopedics, maxillary expansion, and pre-maxillary osteotomy are associated with the periodontal bone support of MCI.Retrospective radiographic study.Tertiary care children's hospital.One hundred seventy-nine patients with BCCLP (22 syndromic) who had post-operative ABG cone beam computed tomography (CBCT) scans taken between 2002-2018.Crown to root (C/R) ratio of MCI measured on CBCT scans.The C/R ratio in 65% of MCI indicated periodontally compromised teeth. Presence of a MLI improved bone support on adjacent MCI when compared to those missing a MLI (51.4% vs 28.4%, P = .010). There was no significant difference in C/R ratios for syndromic diagnosis, age at ABG, history of dentofacial orthopedics, maxillary expansion, and pre-maxillary osteotomy.The majority of MCI in patients with BCCLP are periodontally compromised but bone support is improved when cleft adjacent lateral incisors are present.

18.
Disabil Rehabil ; : 1-18, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37231592

RESUMO

PURPOSE: Physical therapy (PT) plays a central role in treating individuals with Generalized Hypermobility Spectrum Disorder (G-HSD) and Hypermobile Ehlers-Danlos Syndrome (hEDS). However, there is limited research describing these individuals' PT management. This review aims to systematically map the evidence on PT interventions to treat this patient population. METHODS: A systematic literature search of PubMed, CINAHL, and Embase from January 2000 to April 2023 was performed. After the screening process, studies were appraised and classified based on the type of PT interventions used. Five reviewers independently assessed the articles. RESULTS: The search produced 757 articles. Twenty-eight met the inclusion criteria. The studies included 630 participants, mostly female, with a mean age of 26.2 (ranging from 2 to 69). The PT interventions used were therapeutic exercise, patient instruction, motor function training, adaptive equipment, manual therapy, and functional training. CONCLUSIONS: The evidence indicates that therapeutic exercise and motor function training are efficacious methods to treat individuals with G-HSD and hEDS. There is also weak evidence for using adaptive equipment, patient instruction, manual therapy, and functional training. Recent studies emphasize multidisciplinary care and understanding of the psychological impact of G-HSD/hEDS. Additional research is needed to determine the effectiveness and dosage of PT interventions.IMPLICATIONS FOR REHABILITATIONThe lack of guidelines and consensus on physical therapy (PT) interventions to treat and restore function in people with Generalized Hypermobility Spectrum Disorder (G-HSD) and hypermobile Ehlers-Danlos Syndrome (hEDS) challenges clinicians.This review supports therapeutic exercise and motor function training to improve function, well-being, and quality of life in people with G-HSD and hEDS.There is weak evidence for using adaptive equipment, patient instruction, manual therapy, and functional training.We have gathered existing evidence, appraised the quality, and drawn conclusions on this population's most supported PT interventions.

19.
Nat Ecol Evol ; 7(7): 981-993, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36959239

RESUMO

Sexual dimorphism is one of the most prevalent, and often the most extreme, examples of phenotypic variation within species, and arises primarily from genomic variation that is shared between females and males. Many sexual dimorphisms arise through sex differences in gene expression, and sex-biased expression is one way that a single, shared genome can generate multiple, distinct phenotypes. Although many sexual dimorphisms are expected to result from sexual selection, and many studies have invoked the possible role of sexual selection to explain sex-specific traits, the role of sexual selection in the evolution of sexually dimorphic gene expression remains difficult to differentiate from other forms of sex-specific selection. In this Review, we propose a holistic framework for the study of sex-specific selection and transcriptome evolution. We advocate for a comparative approach, across tissues, developmental stages and species, which incorporates an understanding of the molecular mechanisms, including genomic variation and structure, governing gene expression. Such an approach is expected to yield substantial insights into the evolution of genetic variation and have important applications in a variety of fields, including ecology, evolution and behaviour.


Assuntos
Seleção Sexual , Transcriptoma , Feminino , Masculino , Animais , Seleção Genética , Caracteres Sexuais
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