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1.
Artigo em Inglês | MEDLINE | ID: mdl-36361473

RESUMO

During the COVID-19 pandemic, university students have adopted measures that completely transformed their educational environment, and this has generated an increase in psychological stress. The present study aimed to identify the factors associated with anxiety, depression, and stress in students at a university in Peru during the COVID-19 pandemic in 2020. We conducted a cross-sectional analytical study in students in Lima, Peru. The DASS-21 scale was used to measure levels of depression, anxiety, and stress and associate it with socio-educational and COVID-19-related variables using generalized linear models with Poisson distribution, log link, and robust variance. Of 400 students surveyed, 19.2%, 23.2% and 17.2% of students presented depression, anxiety, and stress, respectively. The frequency of depression (PR = 0.91, 95%CI: 0.84-0.99), anxiety (PR = 0.90, 95%CI: 0.83-0.99) and stress (PR = 0.92, 95%CI: 0.86-0.99) was lower in women. The students of the engineering and business faculty presented a higher frequency of anxiety (PR = 1.11, 95%CI: 1.00-1.22). There was a greater frequency of presenting anxiety, depression and stress in students who worked in a different area of health or did not work. Our results suggest the importance of promoting mental health awareness campaigns in university students due to the constant academic load they have.


Assuntos
COVID-19 , Feminino , Humanos , COVID-19/epidemiologia , Pandemias , Peru/epidemiologia , Universidades , Depressão/epidemiologia , Depressão/psicologia , SARS-CoV-2 , Estudos Transversais , Saúde Mental , Ansiedade/epidemiologia , Ansiedade/psicologia , Estresse Psicológico/epidemiologia , Estresse Psicológico/psicologia , Estudantes/psicologia
2.
J Dent Res ; : 220345221128226, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36314491

RESUMO

Patients with persistent orofacial pain (POFP) can go through complex care pathways to receive a diagnosis and management, which can negatively affect their pain. This study aimed to describe 44-y trends in attendances at Welsh medical practices for POFP and establish the number of attendances per patient and referrals associated with orofacial pain and factors that may predict whether a patient is referred. A retrospective observational study was completed using the nationwide Secure Anonymised Information Linkage Databank of visits to general medical practices in Wales (UK). Data were extracted using diagnostic codes ("Read codes"). Orofacial and migraine Read codes were extracted between 1974 and 2017. Data were analyzed using descriptive statistics and univariate and multivariable logistic regression. Over the 44-y period, there were 468,827 POFP and migraine diagnostic codes, accounting for 468,137 patient attendances, or 301,832 patients. The overall attendance rate was 4.22 attendances per 1,000 patient-years (95% confidence interval [CI], 4.21-4.23). The attendance rate increased over the study period. Almost one-third of patients (n = 92,192, 30.54%) attended more than once over the study period, and 15.83% attended more than once within a 12-mo period. There were 20,103 referral codes that were associated with 8,183 patients, with over half these patients being referred more than once. Odds of receiving a referral were highest in females (odds ratio [OR], 1.23; 95% CI, 1.17-1.29), in those living in rural locations (OR, 1.17; 95% CI, 1.12-1.22), and in the least deprived quintile (OR, 1.39; 95% CI, 1.29-1.48). Odds also increased with increasing age (OR, 1.03; 95% CI, 1.03-1.03). The increasing attendance may be explained by the increasing incidence of POFP within the population. These patients can attend on a repeated basis, and very few are referred, but when they are, this may occur multiple times; therefore, current care pathways could be improved.

3.
Rhinology ; 60(6): 402-410, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36150160

RESUMO

BACKGROUND: There is a paucity of reporting on recurrence patterns of de-novo sinonasal squamous cell carcinoma (DN-SCC) and inverted-papilloma-transformed sinonasal squamous cell carcinoma (IP-SCC). METHOD: A systematic literature review queried studies comparing recurrence patterns in patients with both DN-SCC and IP-SCC. Primary outcomes included local and regional recurrence and rates of distant metastasis. Of the 595 studies screened, eight were included. RESULTS: Patients with DN-SCC had significantly higher rates of positive margins, advanced T classification (T3/T4), treatment with chemotherapy and radiotherapy. There were no significant differences in local recurrence or regional recurrence. Overall risk of distant metastasis was lower in IP-SCC. DN-SCC, compared to IP-SCC, is more likely to present with advanced TNM classification and have positive margins after surgical resection, which may affect rates of distant metastasis and recurrence. CONCLUSIONS: The findings in this study suggest IP-SCC may be a less aggressive malignancy compared to DN-SCC, with the possibility of a reduced role for adjuvant therapy in IP-SCC. Further studies are required to better understand differences in tumor biology and treatments strategies between IP-SCC and DN-SCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Nasais , Papiloma Invertido , Neoplasias dos Seios Paranasais , Humanos , Papiloma Invertido/cirurgia , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/patologia , Neoplasias dos Seios Paranasais/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos , Neoplasias Nasais/terapia , Neoplasias Nasais/patologia
4.
Br Poult Sci ; 63(5): 662-669, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35320033

RESUMO

1. Two experiments were conducted to investigate whether the use of phytase in the pre-experimental or experimental phases of true pre-caecal phosphorus digestibility (TPD) assay influenced the assayed TPD values. In experiments 1 and 2, broiler chickens were randomly allocated to 12 treatments in a 2 × 2 × 3 factorial arrangement. The factors were pre-experimental phytase supplementation (+ or -), experimental phase phytase supplementation (+ or -) with varying soybean meal inclusion levels (450, 560, or 670 g/kg).2. The diets in the pre-experimental phase were based on maize-soybean meal, whereas the diet used during the experimental phase was semi-purified, with soybean meal as the only source of P. Both TPD and true phosphorus retention (TPR) were determined using regression for the P output (g/kg, dry matter basis), pre-caecal or total tract, against P intake (g/kg). Data for TPD and TPR were analysed as a 2 × 2 factorial (with or without pre-experimental or experimental phase phytase).3. In both experiments 1 and 2, there were no significant effects for pre-experimental phytase supplementation nor interaction of pre- and experimental phytase supplementation on any of the pre-caecal digestibility responses. Phytase supplementation during the experimental phase increased (P < 0.01) pre-caecal P digestibility and retention, as well as digestible and retained P intake, and decreased (P < 0.01) P output.4. In experiment 1, pre- and experimental phytase supplementation increased (P < 0.01) the coefficient of TPR. In experiment 2, there was no significant effect of pre-experimental phytase supplementation on coefficient of pre-caecal TPD. However, phytase supplementation in the experimental phase increased (P < 0.01) the coefficient of pre-caecal TPD.5. In conclusion, whether or not phytase was supplemented to a P-adequate diet in the pre-experimental phase of the TPD assay, it had no influence on assayed TPD or TPR value.


Assuntos
6-Fitase , Fósforo na Dieta , Animais , Fósforo , Ração Animal/análise , Digestão , Galinhas/fisiologia , Dieta/veterinária , Suplementos Nutricionais , Soja
5.
Rev. cuba. med. mil ; 51(1)mar. 2022.
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1408775

RESUMO

RESUMEN Introducción: El rendimiento académico universitario puede verse afectado por diversos factores personales y ambientales. Objetivo: Determinar los factores asociados al rendimiento académico en estudiantes de medicina de una universidad peruana. Métodos: Estudio transversal realizado en 247 estudiantes del primer al noveno ciclo. Se recopiló las calificaciones de la asignatura con el mayor número de créditos y se aplicó una encuesta para recolectar datos sobre sexo, estado civil, carrera previa, estado laboral y nivel de ansiedad. Se realizó un análisis de regresión simple y múltiple para estimar la asociación entre el rendimiento académico y las variables sociodemográficas de los encuestados. Resultados: El 70 % fueron mujeres, la mediana de edad fue 21 años. El 79,4 % reportó haber culminado una carrera. Casi la cuarta parte reportó tener una actividad laboral (24,3 %). El 46,2 % de universitarios presentó ansiedad. La mediana de nota obtenida fue 16 puntos. En el análisis de regresión simple se encontró que haber realizado una carrera previa (p= 0,044) y tener actividad laboral (p= 0,038) estuvieron asociados positivamente al puntaje de rendimiento académico. Sin embargo, en el análisis de regresión múltiple, no se mantuvo las diferencias observadas en ambas variables (p> 0,05). Conclusión: La mediana de nota en el período de estudio es 16 puntos. La mayoría tiene carrera previa y casi un tercio se encuentra laborando. La prevalencia de ansiedad es importante. Sin embargo, no se observa una asociación estadísticamente significativa entre los factores estudiados y el rendimiento académico.


ABSTRACT Introduction: University academic performance can be affected by various personal and environmental factors. Objective: To determine the factors associated with academic performance in medical students at a Peruvian university. Methods: Cross-sectional study conducted in 247 students from the first to the ninth cycle. The grades of the subject with the highest number of credits were collected and a survey was applied to collect data on sex, marital status, previous career, work status, and anxiety level. A simple and multiple regression analysis was performed to estimate the association between academic performance and sociodemographic variables of the respondents. Results: 70 % were female, median age was 21 years. Seventy-nine-point four percent reported having completed a career. Almost a quarter reported having a job (24,3 %). Anxiety was reported by 46,2 % of university students. The median grade obtained was 16 points. In the simple regression analysis, it was found that having a previous career (p= 0,044) and having a job (p= 0,038) were positively associated with the academic performance score. However, in the multiple regression analysis, the differences observed in both variables were not maintained (p> 0,05). Conclusion: The median grade in the study period is 16 points. Most of them have a previous career and almost a third are working. The prevalence of anxiety is significant. However, there is no statistically significant association between the factors studied and academic performance.

6.
Environ Entomol ; 51(1): 216-221, 2022 02 16.
Artigo em Inglês | MEDLINE | ID: mdl-34907417

RESUMO

Wild Callery pear (Pyrus calleryana Decne.) results from a cross between various cultivars of P. calleryana and any other Pyrus individual. While many cultivars of this species are still commercially produced and sold for horticultural purposes in the United States, Callery pear is a detrimental invasive species that encroaches on many managed and natural areas, damages equipment and injures people, pets, and livestock with its thorny branches, and likely causes detrimental ecological impacts. Despite its importance as an invasive species, the mechanisms behind Callery pear's invasion and spread are unclear. To identify potential drivers of invasion, we quantified feeding of generalist and specialist herbivores on Callery pear and four native tree species, based on insect host ranges, with choice and no-choice experiments followed by field surveys of herbivory on these same tree species. Feeding by all herbivores was lower on Callery pear than on native tree species in no-choice assays. Specifically, feeding on Callery pear was moderate by generalists and very low by specialists. Specialist feeding on Callery pear was comparable to native species in choice assays but was significantly reduced in no-choice assays. Reduced specialist feeding along with moderate generalist feeding on Callery pear in the field provides evidence for the Enemy Release Hypothesis as a potential driving mechanism behind its invasion success.


Assuntos
Pyrus , Rosaceae , Rosales , Animais , Herbivoria , Humanos , Espécies Introduzidas
7.
Rev. cuba. med. mil ; 51(3): e2105, 2022. tab, graf
Artigo em Espanhol | LILACS-Express | LILACS | ID: biblio-1408850

RESUMO

RESUMEN Introducción: El personal sanitario representa la primera respuesta del sistema de salud en la pandemia de la COVID-19, por ello, es importante valorar su conocimiento sobre la identificación y atención de pacientes con la COVID-19. Objetivo: Identificar los factores asociados a la percepción del conocimiento de médicos residentes ante la atención de pacientes con la COVID-19 y describir la percepción de la salud mental durante la pandemia de la COVID-19. Métodos: Estudio transversal, realizado en 2020 en hospitales del Perú. Se empleó la escala "Perception of Knowledge in Health Workers" (alpha de Cronbach: 0,77). También, se empleó la escala "Mental Health COVID-19" (alpha de Cronbach: 0,88). Se realizó estadística bivariada y multivariada. Resultados: De los 200 encuestados, el 12 % y 5 % manifestaron que eran capaces de reconocer a un caso sospechoso y atender un paciente diagnosticado, respectivamente. El 41 % y 35 % estuvo muy de acuerdo con el miedo/preocupación de contagiar a su familia y sentir el maltrato por los pocos equipos de protección personal, respectivamente. En el análisis multivariado, la percepción del conocimiento se asoció a trabajar en emergencias (p= 0,007), a la cantidad de amistades positivos a la COVID-19 (p= 0,012) y a realizar recientemente una intubación (p= 0,035); estas fueron ajustadas por el puntaje de la percepción de salud mental. Conclusiones: Trabajar en emergencias, haber tenido contacto con pacientes contagiados y haber realizado procedimientos médico-quirúrgicos influyen en la percepción de conocimientos de los médicos sobre la atención de pacientes con la COVID-19.


ABSTRACT Introduction: Health personnel represent the first response of the health system in the COVID-19 pandemic. Therefore, it is important to assess their knowledge about the identification and care of patients with COVID-19. Objective: To identify the factors associated with the perception of knowledge of Peruvian resident physicians regarding the care of patients with COVID-19 and to describe the perception of mental health during the COVID-19 pandemic. Methods: Cross-sectional study, carried out in 2020 in hospitals in Peru. The "Perception of Knowledge in Health Workers" scale was used (Cronbach's Alpha: 0.77). And also, the "Mental Health COVID-19" scale was used (Cronbach's Alpha: 0.88). Bivariate and multivariate statistics were performed. Results: Of the 200 respondents, 12% and 5% stated that they were able to recognize a suspected case and care for a diagnosed patient, respectively; 41% and 35% strongly agreed with the fear/concern of infecting their family and feeling mistreatment due to the lack of personal protective equipment, respectively. In the multivariate analysis, the perception of knowledge was associated with working in emergencies (p= 0.007), with the number of positive friends for COVID-19 (p= 0.012) and with having recently undergone intubation (p= 0.035); these were adjusted by the mental health perception score. Conclusions: Working in emergencies, having had contact with infected patients and having performed medical-surgical procedures influence the perception of knowledge of doctors about the care of patients with COVID-19.

8.
Genet Med ; 23(11): 2087-2095, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34262154

RESUMO

PURPOSE: Ataxia-Telangiectasia Mutated (ATM) has been implicated in the risk of several cancers, but establishing a causal relationship is often challenging. Although ATM single-nucleotide polymorphisms have been linked to melanoma, few functional alleles have been identified. Therefore, ATM impact on melanoma predisposition is unclear. METHODS: From 22 American, Australian, and European sites, we collected 2,104 familial, multiple primary (MPM), and sporadic melanoma cases who underwent ATM genotyping via panel, exome, or genome sequencing, and compared the allele frequency (AF) of selected ATM variants classified as loss-of-function (LOF) and variants of uncertain significance (VUS) between this cohort and the gnomAD non-Finnish European (NFE) data set. RESULTS: LOF variants were more represented in our study cohort than in gnomAD NFE, both in all (AF = 0.005 and 0.002, OR = 2.6, 95% CI = 1.56-4.11, p < 0.01), and familial + MPM cases (AF = 0.0054 and 0.002, OR = 2.97, p < 0.01). Similarly, VUS were enriched in all (AF = 0.046 and 0.033, OR = 1.41, 95% CI = 1.6-5.09, p < 0.01) and familial + MPM cases (AF = 0.053 and 0.033, OR = 1.63, p < 0.01). In a case-control comparison of two centers that provided 1,446 controls, LOF and VUS were enriched in familial + MPM cases (p = 0.027, p = 0.018). CONCLUSION: This study, describing the largest multicenter melanoma cohort investigated for ATM germline variants, supports the role of ATM as a melanoma predisposition gene, with LOF variants suggesting a moderate-risk.


Assuntos
Ataxia Telangiectasia , Melanoma , Proteínas Mutadas de Ataxia Telangiectasia/genética , Austrália , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Humanos , Melanoma/genética
9.
Bioresour Technol ; 335: 125224, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33984554

RESUMO

A two-stage dilute acid and steam explosion (SE) pretreatment process was developed and evaluated at pilot scale for ethanol production from cotton gin trash (CGT). Optimal conditions for CGT processing were defined as 1:6 solids to liquids ratio with 9% H2SO4 wt. on solids at 180 °C for 15 min. during stage 1 with ensuing pressed fibres successively exposed to SE at 200 °C for 5 min during stage 2. SE fibres were highly acquiescent to enzyme hydrolysis (76%) in the presence of PEG 6000, yielding 381 g glucose kg-1 fibre. Simultaneous saccharification and fermentation (SSF) trials validated the selected process option and additional fed-batch SSFs confirmed titres above the minimum 4% ww-1 benchmark for economically viable distillation. The practicality of converting CGT to ethanol was demonstrated at pilot scale with titres above 4% ww-1 and a conversion efficiency of 60% t-1 dry GCT.


Assuntos
Etanol , Resíduos de Alimentos , Fermentação , Hidrólise , Vapor
10.
Sci Rep ; 11(1): 9718, 2021 05 06.
Artigo em Inglês | MEDLINE | ID: mdl-33958621

RESUMO

Actin nucleation is the key rate limiting step in the process of actin polymerization, and tight regulation of this process is critical to ensure actin filaments form only at specific times and at defined regions of the cell. WH2 domains are short sequence motifs found in many different actin binding proteins including WASP family proteins which regulate the actin nucleating complex Arp2/3. In this study we reveal a phosphorylation site, Serine 554, within the WH2 domain of the yeast WASP homologue Las17. Both phosphorylation and a phospho-mimetic mutation reduce actin monomer binding affinity while an alanine mutation, generated to mimic the non-phosphorylated state, increases actin binding affinity. The effect of these mutations on the Las17-dependent process of endocytosis in vivo was analysed and leads us to propose that switching of Las17 phosphorylation states may allow progression through distinct phases of endocytosis from site assembly through to the final scission stage. While the study is focused on Las17, the sole WASP family protein in yeast, our results have broad implications for our understanding of how a key residue in this conserved motif can underpin the many different actin regulatory roles with which WH2 domains have been associated.


Assuntos
Actinas/metabolismo , Endocitose , Domínios Proteicos , Proteínas de Saccharomyces cerevisiae/metabolismo , Saccharomyces cerevisiae/metabolismo , Proteína da Síndrome de Wiskott-Aldrich/metabolismo , Sequência de Aminoácidos , Mutação , Fosforilação , Polimerização , Ligação Proteica , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Homologia de Sequência de Aminoácidos , Proteína da Síndrome de Wiskott-Aldrich/química , Proteína da Síndrome de Wiskott-Aldrich/genética
11.
Hum Reprod ; 36(7): 1999-2010, 2021 06 18.
Artigo em Inglês | MEDLINE | ID: mdl-34021356

RESUMO

STUDY QUESTION: Does the expansion of genome-wide association studies (GWAS) to a broader range of ancestries improve the ability to identify and generalise variants associated with age at menarche (AAM) in European populations to a wider range of world populations? SUMMARY ANSWER: By including women with diverse and predominantly non-European ancestry in a large-scale meta-analysis of AAM with half of the women being of African ancestry, we identified a new locus associated with AAM in African-ancestry participants, and generalised loci from GWAS of European ancestry individuals. WHAT IS KNOWN ALREADY: AAM is a highly polygenic puberty trait associated with various diseases later in life. Both AAM and diseases associated with puberty timing vary by race or ethnicity. The majority of GWAS of AAM have been performed in European ancestry women. STUDY DESIGN, SIZE, DURATION: We analysed a total of 38 546 women who did not have predominantly European ancestry backgrounds: 25 149 women from seven studies from the ReproGen Consortium and 13 397 women from the UK Biobank. In addition, we used an independent sample of 5148 African-ancestry women from the Southern Community Cohort Study (SCCS) for replication. PARTICIPANTS/MATERIALS, SETTING, METHODS: Each AAM GWAS was performed by study and ancestry or ethnic group using linear regression models adjusted for birth year and study-specific covariates. ReproGen and UK Biobank results were meta-analysed using an inverse variance-weighted average method. A trans-ethnic meta-analysis was also carried out to assess heterogeneity due to different ancestry. MAIN RESULTS AND THE ROLE OF CHANCE: We observed consistent direction and effect sizes between our meta-analysis and the largest GWAS conducted in European or Asian ancestry women. We validated four AAM loci (1p31, 6q16, 6q22 and 9q31) with common genetic variants at P < 5 × 10-7. We detected one new association (10p15) at P < 5 × 10-8 with a low-frequency genetic variant lying in AKR1C4, which was replicated in an independent sample. This gene belongs to a family of enzymes that regulate the metabolism of steroid hormones and have been implicated in the pathophysiology of uterine diseases. The genetic variant in the new locus is more frequent in African-ancestry participants, and has a very low frequency in Asian or European-ancestry individuals. LARGE SCALE DATA: N/A. LIMITATIONS, REASONS FOR CAUTION: Extreme AAM (<9 years or >18 years) were excluded from analysis. Women may not fully recall their AAM as most of the studies were conducted many years later. Further studies in women with diverse and predominantly non-European ancestry are needed to confirm and extend these findings, but the availability of such replication samples is limited. WIDER IMPLICATIONS OF THE FINDINGS: Expanding association studies to a broader range of ancestries or ethnicities may improve the identification of new genetic variants associated with complex diseases or traits and the generalisation of variants from European-ancestry studies to a wider range of world populations. STUDY FUNDING/COMPETING INTEREST(S): Funding was provided by CHARGE Consortium grant R01HL105756-07: Gene Discovery For CVD and Aging Phenotypes and by the NIH grant U24AG051129 awarded by the National Institute on Aging (NIA). The authors have no conflict of interest to declare.


Assuntos
Estudo de Associação Genômica Ampla , Polimorfismo de Nucleotídeo Único , Adolescente , Estudos de Coortes , Etnicidade , Feminino , Humanos , Menarca/genética
12.
Ann R Coll Surg Engl ; 103(9): 673-677, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33956515

RESUMO

AIMS: The aim of this study was to investigate whether the prevalence of hearing loss among arthroplasty surgeons was comparable to clinicians from other medical specialties and to explore the factors associated with hearing loss. METHODS: A cross-sectional prevalence study was carried out. Arthroplasty surgeons and non-surgical clinicians were recruited from orthopaedic and medical conferences. All participants were given a paper questionnaire including demographic details, hearing history and the Tinnitus and Hearing Survey. All participants were screened for hearing loss in a quiet room using the HearCheck Screener™ (HCS; Siemens, Munich, Germany). Logistic regression was used to identify factors associated with hearing loss. All statistical models were adjusted for age, gender, smoking status and personal noise exposure. RESULTS: The HEARS (Hearing Evaluation of ARthroplasty Surgeons) study recruited 188 participants (106 arthroplasty surgeons; 82 non-surgical clinicians). Prevalence of hearing loss identified by the HCS was 31% for arthroplasty surgeons vs 11% for non-surgical clinicians. The odds of failing the HCS were 3.7 times higher in arthroplasty surgeons compared to their non-surgical colleagues (p < 0.004). The odds of self-reported hearing using the Tinnitus and Hearing Survey were 2.79 times higher among arthroplasty surgeons (p < 0.003). CONCLUSION: The prevalence of hearing loss among arthroplasty surgeons is significantly higher than in their non-surgical colleagues. Noise generated during arthroplasty surgery should be recognised and managed to create safer working conditions.


Assuntos
Artroplastia , Perda Auditiva/epidemiologia , Doenças Profissionais/epidemiologia , Ortopedia , Zumbido/epidemiologia , Adulto , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência
13.
BJA Educ ; 21(2): 44-50, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33889429
14.
Cell Mol Life Sci ; 78(10): 4735-4763, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33792748

RESUMO

Neuronal Ceroid Lipofuscinosis (NCL), also known as Batten disease, is an incurable childhood brain disease. The thirteen forms of NCL are caused by mutations in thirteen CLN genes. Mutations in one CLN gene, CLN5, cause variant late-infantile NCL, with an age of onset between 4 and 7 years. The CLN5 protein is ubiquitously expressed in the majority of tissues studied and in the brain, CLN5 shows both neuronal and glial cell expression. Mutations in CLN5 are associated with the accumulation of autofluorescent storage material in lysosomes, the recycling units of the cell, in the brain and peripheral tissues. CLN5 resides in the lysosome and its function is still elusive. Initial studies suggested CLN5 was a transmembrane protein, which was later revealed to be processed into a soluble form. Multiple glycosylation sites have been reported, which may dictate its localisation and function. CLN5 interacts with several CLN proteins, and other lysosomal proteins, making it an important candidate to understand lysosomal biology. The existing knowledge on CLN5 biology stems from studies using several model organisms, including mice, sheep, cattle, dogs, social amoeba and cell cultures. Each model organism has its advantages and limitations, making it crucial to adopt a combinatorial approach, using both human cells and model organisms, to understand CLN5 pathologies and design drug therapies. In this comprehensive review, we have summarised and critiqued existing literature on CLN5 and have discussed the missing pieces of the puzzle that need to be addressed to develop an efficient therapy for CLN5 Batten disease.


Assuntos
Glicoproteínas de Membrana Associadas ao Lisossomo/genética , Lisossomos/metabolismo , Mutação , Lipofuscinoses Ceroides Neuronais/patologia , Animais , Humanos , Glicoproteínas de Membrana Associadas ao Lisossomo/metabolismo , Lipofuscinoses Ceroides Neuronais/etiologia , Lipofuscinoses Ceroides Neuronais/metabolismo
15.
J Laryngol Otol ; 135(6): 555-559, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33875024

RESUMO

OBJECTIVE: For recalcitrant chronic maxillary sinusitis, modified endoscopic medial maxillectomy has been shown to be clinically beneficial after failed maxillary antrostomy as endoscopic medial maxillectomy may offer improved topical therapy delivery. This study compared irrigation patterns after maxillary antrostomy versus endoscopic medial maxillectomy, using computational fluid dynamic modelling. CASE REPORT: A 54-year-old female with left chronic maxillary sinusitis underwent maxillary antrostomy, followed by endoscopic medial maxillectomy. Computational fluid dynamic models were created after each surgery and used to simulate irrigations. RESULTS: After maxillary antrostomy, irrigation penetrated the maxillary sinus at 0.5 seconds, initially contacting the posterior wall. The maxillary sinus was half-filled at 2 seconds, and completely filled at 4 seconds. After endoscopic medial maxillectomy, irrigation penetrated the maxillary sinus at 0.5 seconds and immediately contacted all maxillary sinus walls. The maxillary sinus was completely filled by 2 seconds. CONCLUSION: Computational fluid dynamic modelling demonstrated that endoscopic medial maxillectomy allowed faster, more forceful irrigation to all maxillary sinus walls compared with maxillary antrostomy.


Assuntos
Endoscopia , Maxila/cirurgia , Seio Maxilar/cirurgia , Sinusite Maxilar/cirurgia , Doença Crônica , Feminino , Humanos , Pessoa de Meia-Idade , Estomia , Irrigação Terapêutica
17.
Hum Reprod ; 36(5): 1268-1278, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33595055

RESUMO

STUDY QUESTION: How accurately do women report a diagnosis of endometriosis on self-administered questionnaires? SUMMARY ANSWER: Based on the analysis of four international cohorts, women self-report endometriosis fairly accurately with a > 70% confirmation for clinical and surgical records. WHAT IS KNOWN ALREADY: The study of complex diseases requires large, diverse population-based samples, and endometriosis is no exception. Due to the difficulty of obtaining medical records for a condition that may have been diagnosed years earlier and for which there is no standardized documentation, reliance on self-report is necessary. Only a few studies have assessed the validity of self-reported endometriosis compared with medical records, with the observed confirmation ranging from 32% to 89%. STUDY DESIGN, SIZE, DURATION: We compared questionnaire-reported endometriosis with medical record notation among participants from the Black Women's Health Study (BWHS; 1995-2013), Etude Epidémiologique auprès de femmes de la Mutuelle Générale de l'Education Nationale (E3N; 1990-2006), Growing Up Today Study (GUTS; 2005-2016), and Nurses' Health Study II (NHSII; 1989-1993 first wave, 1995-2007 second wave). PARTICIPANTS/MATERIALS, SETTING, METHODS: Participants who had reported endometriosis on self-administered questionnaires gave permission to procure and review their clinical, surgical, and pathology medical records, yielding records for 827 women: 225 (BWHS), 168 (E3N), 85 (GUTS), 132 (NHSII first wave), and 217 (NHSII second wave). We abstracted diagnosis confirmation as well as American Fertility Society (AFS) or revised American Society of Reproductive Medicine (rASRM) stage and visualized macro-presentation (e.g. superficial peritoneal, deep endometriosis, endometrioma). For each cohort, we calculated clinical reference to endometriosis, and surgical- and pathologic-confirmation proportions. MAIN RESULTS AND THE ROLE OF CHANCE: Confirmation was high-84% overall when combining clinical, surgical, and pathology records (ranging from 72% for BWHS to 95% for GUTS), suggesting that women accurately report if they are told by a physician that they have endometriosis. Among women with self-reported laparoscopic confirmation of their endometriosis diagnosis, confirmation of medical records was extremely high (97% overall, ranging from 95% for NHSII second wave to 100% for NHSII first wave). Importantly, only 42% of medical records included pathology reports, among which histologic confirmation ranged from 76% (GUTS) to 100% (NHSII first wave). Documentation of visualized endometriosis presentation was often absent, and details recorded were inconsistent. AFS or rASRM stage was documented in 44% of NHSII first wave, 13% of NHSII second wave, and 24% of GUTS surgical records. The presence/absence of deep endometriosis was rarely noted in the medical records. LIMITATIONS, REASONS FOR CAUTION: Medical record abstraction was conducted separately by cohort-specific investigators, potentially introducing misclassification due to variation in abstraction protocols and interpretation. Additionally, information on the presence/absence of AFS/rASRM stage, deep endometriosis, and histologic findings were not available for all four cohort studies. WIDER IMPLICATIONS OF THE FINDINGS: Variation in access to care and differences in disease phenotypes and risk factor distributions among patients with endometriosis necessitates the use of large, diverse population samples to subdivide patients for risk factor, treatment response and discovery of long-term outcomes. Women self-report endometriosis with reasonable accuracy (>70%) and with exceptional accuracy when women are restricted to those who report that their endometriosis had been confirmed by laparoscopic surgery (>94%). Thus, relying on self-reported endometriosis in order to use larger sample sizes of patients with endometriosis appears to be valid, particularly when self-report of laparoscopic confirmation is used as the case definition. However, the paucity of data on histologic findings, AFS/rASRM stage, and endometriosis phenotypic characteristics suggests that a universal requirement for harmonized clinical and surgical data documentation is needed if we hope to obtain the relevant details for subgrouping patients with endometriosis. STUDY FUNDING/COMPETING INTEREST(S): This project was supported by Eunice Kennedy Shriver National Institute of Child Health and Development grants HD48544, HD52473, HD57210, and HD94842, National Cancer Institute grants CA50385, R01CA058420, UM1CA164974, and U01CA176726, and National Heart, Lung, and Blood Institute grant U01HL154386. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. AS, SM, and KT were additionally supported by the J. Willard and Alice S. Marriott Foundation. MK was supported by a Marie Curie International Outgoing Fellowship within the 7th European Community Framework Programme (#PIOF-GA-2011-302078) and is grateful to the Philippe Foundation and the Bettencourt-Schueller Foundation for their financial support. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. LA Wise has served as a fibroid consultant for AbbVie, Inc for the last three years and has received in-kind donations (e.g. home pregnancy tests) from Swiss Precision Diagnostics, Sandstone Diagnostics, Kindara.com, and FertilityFriend.com for the PRESTO cohort. SA Missmer serves as an advisory board member for AbbVie and a single working group service for Roche; neither are related to this study. No other authors have a conflict of interest to report. Funders had no role in the study design, conduct of the study or data analysis, writing of the report, or decision to submit the article for publication. TRIAL REGISTRATION NUMBER: N/A.


Assuntos
Endometriose , Criança , Estudos de Coortes , Endometriose/diagnóstico , Endometriose/epidemiologia , Feminino , Fertilidade , Humanos , Gravidez , Fatores de Risco , Autorrelato
18.
BMC Cancer ; 21(1): 10, 2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33402120

RESUMO

BACKGROUND: Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) represent a heterogenous group of tumors. Findings from the phase III NETTER-1 trial showed that treatment of unresectable/metastatic progressive gastrointestinal (GI) NETs with 177Lu-Dotatate resulted in a significant improvement in progression-free survival (PFS) and overall survival (OS) compared with best supportive care (BSC) with high dose octreotide long-acting repeatable (LAR) 60 mg. A health economic analysis was performed using input data from clinical studies and data derived from an indirect comparison to determine the cost-effectiveness of 177Lu-Dotatate in the treatment of GI-NETs and pancreatic NETs (P-NETs) in Scotland. METHODS: Cost-effectiveness analysis was performed from the payer perspective using a three-state partitioned survival model. In the base case 177Lu-Dotatate was compared with BSC in gastrointestinal (GI)-NETs using clinical data from the NETTER-1 trial. A secondary analysis comparing 177Lu-Dotatate with BSC, everolimus or sunitinib in patients with P-NETs was also performed using hazard ratios inferred from indirect comparisons. The base case analysis was performed over a 20-year time horizon with an annual discount rate of 3.5% for both costs and clinical outcomes. RESULTS: For unresectable/metastatic progressive GI-NETs treatment with 177Lu-Dotatate led to a gain in quality-adjusted life expectancy of 1.33 quality-adjusted life years (QALYs) compared with BSC due to extended PFS and OS. Mean total lifetime costs were GBP 35,701 higher with 177Lu-Dotatate, leading to an incremental cost-effectiveness ratio (ICER) of GBP 26,830 per QALY gained. In analyses in patients with P-NETs 177Lu-Dotatate was associated with ICERs below GBP 30,000 per QALY gained in comparisons with BSC, sunitinib and everolimus. CONCLUSIONS: Cost-effectiveness analyses demonstrated that, in Scotland, from the payer perspective, 177Lu-Dotatate at the set acquisition cost is a cost-effective treatment option for patients with unresectable or metastatic progressive GI-NETs or P-NETs.


Assuntos
Análise Custo-Benefício , Neoplasias Intestinais/economia , Neoplasias Intestinais/radioterapia , Lutécio/economia , Tumores Neuroendócrinos/economia , Tumores Neuroendócrinos/radioterapia , Octreotida/química , Compostos Organometálicos/economia , Neoplasias Pancreáticas/economia , Neoplasias Pancreáticas/radioterapia , Compostos Radiofarmacêuticos/economia , Neoplasias Gástricas/economia , Neoplasias Gástricas/radioterapia , Progressão da Doença , Seguimentos , Humanos , Neoplasias Intestinais/patologia , Lutécio/uso terapêutico , Metástase Neoplásica , Tumores Neuroendócrinos/patologia , Compostos Organometálicos/uso terapêutico , Neoplasias Pancreáticas/patologia , Prognóstico , Anos de Vida Ajustados por Qualidade de Vida , Compostos Radiofarmacêuticos/uso terapêutico , Neoplasias Gástricas/patologia
19.
J Foot Ankle Res ; 14(1): 4, 2021 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-33413562

RESUMO

BACKGROUND: Foot health problems are common in the general population, and particularly so in people with rheumatic and musculoskeletal disorders (RMD). Several clinical guidelines state that people with RMDs should have access to foot health services, although service capacity is often limited. The current COVID-19 pandemic has increased the need for alternative ways to provide patient care. The aim of this clinical audit was to review a newly implemented telephone follow-up appointment service conducted within the Rheumatology Podiatry Department in Leeds, UK. METHODS: Fifty-eight patients attending the Rheumatology Podiatry Department at Leeds Teaching Hospitals NHS Trust were contacted by telephone approximately 6-8 weeks following initial intervention. During the telephone consultation, all patients were asked pre-defined questions relating to their symptoms, intervention efficacy, the need for further appointments and their preference for the type of consultation. To assess the cost of the telephone consultation the number of attempts needed in order to make successful contact, the duration of the call and the number of telephone follow-up appointments completed in a working day were also recorded. RESULTS: Twenty-five patients (43%) were successfully contacted within the 6-8 weeks stipulated time frame and were included in the analysis. Of the 25 contacted, twelve (48%) patients were successfully contacted on the first attempt. Ten (40%) were successfully contacted on the second attempt. The remaining three patients (12%) required 3 or more attempts to make successful contact. Telephone consultations were estimated not to last longer than 10 min, including notes screening and documentation. Eleven patients (44%) reported an improvement in their symptoms, thirteen (52%) reported no change and one patient (4%) reported their symptoms to be worse. CONCLUSION: Telephone follow-up consultations may be a potentially cost-effective alternative to face-to-face appointments when implemented in a Rheumatology Podiatry Department, and provide an alternative way of providing care, especially when capacity for face-to-face contact is limited. The potential cost saving and efficiency benefits of this service are likely to be enhanced when telephone consultations are pre-arranged with patients.


Assuntos
COVID-19/epidemiologia , Doenças Musculoesqueléticas/epidemiologia , Pandemias , Podiatria/organização & administração , Encaminhamento e Consulta , Telefone , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Musculoesqueléticas/diagnóstico , Estudos Retrospectivos , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/epidemiologia , SARS-CoV-2
20.
Arthritis Care Res (Hoboken) ; 73(8): 1114-1124, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-32374918

RESUMO

OBJECTIVE: Though randomized controlled trials have demonstrated relatively comparable clinical outcomes with triple therapy (methotrexate [MTX], sulfasalazine [SSZ], and hydroxychloroquine [HCQ]) compared to combination therapy (tumor necrosis factor inhibitor [TNFi] and MTX), real-world experiences comparing these strategies have not been well studied. METHODS: We evaluated the clinical effectiveness and effects of medication discontinuation of triple therapy with MTX/SSZ/HCQ versus combination therapy with TNFi/MTX in rheumatoid arthritis (RA) patients enrolled in the Corrona RA Drug Safety & Effectiveness Registry. Propensity score matching was used to match patients up to a ratio of 1:3 to adjust for imbalances between treatment groups, with stratification performed according to biologics-naive or biologics-exposed status of study participants. RESULTS: Patients eligible for analysis in this study included biologics-naive RA patients (3,926 who received combination therapy with TNFi/MTX and 262 who received triple therapy with MTX/SSZ/HCQ) and biologics-exposed RA patients (3,365 who received combination therapy with TNFi/MTX and 130 patients who received triple therapy with MTX/SSZ/HCQ). Before propensity score matching, numerous factors were imbalanced between the treatment groups, with triple therapy patients generally being older, having a longer disease duration of RA and lower RA disease activity, and more likely having a history of malignancy and other comorbidities. After matching, almost all (93-98%) triple therapy patients could be matched to TNFi/MTX therapy patients, and cohort characteristics were generally well balanced. Discontinuation of medication was greater in triple therapy patients referent to TNFi/MTX therapy patients (adjusted hazard ratio [HR] of 2.17 [95% confidence interval 1.63-2.88] in the biologics-naive group; adjusted HR of 1.51 [95% confidence interval 1.06-2.15] in the biologics-exposed group). At 6 months, the proportion of biologics-naive patients attaining low disease activity was significantly greater in the TNFi/MTX treatment group (49.2% in TNFi/MTX therapy patients versus 33.3% in triple therapy patients), as was the mean change in Clinical Disease Activity Index scores (-9.3 units versus -5.5 [95% confidence interval -1.5, -6.1]). Corresponding results in the biologics-exposed patients numerically favored TNFi/MTX therapy compared to triple therapy but did not reach statistical significance. CONCLUSION: Few patients receive triple therapy with MTX/SSZ/HCQ in the US. In the present study, drug persistence and clinical effectiveness outcomes were less favorable in triple therapy patients compared to TNFi/MTX therapy patients.


Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Antirreumáticos/uso terapêutico , Artrite Reumatoide/tratamento farmacológico , Produtos Biológicos/uso terapêutico , Hidroxicloroquina/uso terapêutico , Metotrexato/uso terapêutico , Sulfassalazina/uso terapêutico , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adulto , Idoso , Anti-Inflamatórios não Esteroides/efeitos adversos , Antirreumáticos/efeitos adversos , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/imunologia , Produtos Biológicos/efeitos adversos , Quimioterapia Combinada , Feminino , Humanos , Hidroxicloroquina/efeitos adversos , Masculino , Metotrexato/efeitos adversos , Pessoa de Meia-Idade , Sistema de Registros , Sulfassalazina/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/efeitos adversos , Estados Unidos
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