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1.
J Pediatr Orthop ; 41(2): 77-82, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33229963

RESUMO

INTRODUCTION: Trochlear dysplasia is a known risk factor for patellar dislocations yet normal trochlea development is not well described. This study will define the articular cartilage (AC) and subchondral trochlear morphology development in pediatric patients using magnetic resonance imaging (MRI) evaluation. METHODS: A retrospective knee MRI review included patients aged 3 to 16 years with nonpatellofemoral-related diagnoses. International classification of diseases-9/International classification of diseases-10 codes were used to identify eligible study patients. Measurements of the trochlea were made on the basis of previously established methods using the axial MRI just distal to the physis at the deepest portion of the trochlear groove. Three linear [lateral trochlear height (LTH), medial trochlear height (MTH), and central trochlear height (CTH)] and 3 angular [sulcus angle (SA), lateral trochlear slope (LTS), and medial trochlear slope (MTS)] were made at AC and subchondral bone (SCB). The 12 measurements were made independently by 2 study authors. Inter-rater reliability was assessed using an interclass correlation coefficient for absolute agreement to the average of the scores. Trochlea measurements were summarized across age quartiles defined as first quartile (age, 5.1 to 8.3 y), second quartile (8.3 to 11.5 y), third quartile (11.5 to 14.3 y), fourth quartile (14.3to 16.9 y). Associations between age and trochlea measures were assessed using linear regression with Huber-White-adjusted SEs to account for clustering from a small number of patients (N=16) with >1 MRI. RESULTS: In total, 246 knee MRIs from 230 patients were included in this study; 113 patients (51%) were female, whereas 117 (49%) were male. A total of 116 MRIs (47%) were of the left knee and 130 (53%) were right knee. The average patient age was 11.4±3.4 years. Inter-rater agreement was high across all measures with interclass correlation coefficient values >0.7. Mean values for measurements are presented by age quartiles. LTH, MTH, and CTH showed a linear increase with age (range, 2 to 2.6 cm/y; P<0.001). SA, LTS, MTS measured at AC showed no change with age (P>0.05); however, LTS and MTS measured at SCB showed significant increases with age (0.6 and 0.9 degrees/y; P<0.001), whereas SA showed a decrease with age (-1.4 degrees/y; P<0.001). There were no significant differences found in the age associations by laterality, left versus right. There were no sex differences in the age associations for SA, LTS (P>0.05); however, for MTH, LTH, and CTH, males were found to have a significantly greater growth rate (P<0.001). CONCLUSIONS: This study found an increase in AC and SCB MTH, LTH, and CTH over time, as well as an increase in SCB LTS and MTS, with a decrease in SA. However, AC of the LTS and SA remained constant, with no significant change throughout growth. This normative data indicate that the LTS and SA of AC are predictors of final trochlea shape in normal development. Final trochlear morphologic development is nearly complete around age 12 years, with no significant changes occurring thereafter.


Assuntos
Articulação do Joelho/anatomia & histologia , Adolescente , Doenças do Desenvolvimento Ósseo/cirurgia , Cartilagem Articular/anatomia & histologia , Cartilagem Articular/diagnóstico por imagem , Criança , Pré-Escolar , Feminino , Lâmina de Crescimento/anatomia & histologia , Lâmina de Crescimento/diagnóstico por imagem , Humanos , Instabilidade Articular/cirurgia , Articulação do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Reprodutibilidade dos Testes , Estudos Retrospectivos , Caracteres Sexuais
2.
MMWR Morb Mortal Wkly Rep ; 69(15): 458-464, 2020 04 17.
Artigo em Inglês | MEDLINE | ID: mdl-32298251

RESUMO

Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.


Assuntos
COVID-19 , Diabetes Mellitus , Humanos , Masculino , Estados Unidos/epidemiologia , Idoso , Feminino , COVID-19/epidemiologia , COVID-19/terapia , SARS-CoV-2 , Vigilância da População , Hospitalização
3.
MMWR Morb Mortal Wkly Rep ; 69(38): 1347-1354, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32970655

RESUMO

Pregnant women might be at increased risk for severe coronavirus disease 2019 (COVID-19) (1,2). The COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) (3) collects data on hospitalized pregnant women with laboratory-confirmed SARS-CoV-2, the virus that causes COVID-19; to date, such data have been limited. During March 1-August 22, 2020, approximately one in four hospitalized women aged 15-49 years with COVID-19 was pregnant. Among 598 hospitalized pregnant women with COVID-19, 54.5% were asymptomatic at admission. Among 272 pregnant women with COVID-19 who were symptomatic at hospital admission, 16.2% were admitted to an intensive care unit (ICU), and 8.5% required invasive mechanical ventilation. During COVID-19-associated hospitalizations, 448 of 458 (97.8%) completed pregnancies resulted in a live birth and 10 (2.2%) resulted in a pregnancy loss. Testing policies based on the presence of symptoms might miss COVID-19 infections during pregnancy. Surveillance of pregnant women with COVID-19, including those with asymptomatic infections, is important to understand the short- and long-term consequences of COVID-19 for mothers and newborns. Identifying COVID-19 in women during birth hospitalizations is important to guide preventive measures to protect pregnant women, parents, newborns, other patients, and hospital personnel. Pregnant women and health care providers should be made aware of the potential risks for severe COVID-19 illness, adverse pregnancy outcomes, and ways to prevent infection.


Assuntos
Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Complicações Infecciosas na Gravidez/terapia , Complicações Infecciosas na Gravidez/virologia , Resultado da Gravidez/epidemiologia , Adolescente , Adulto , Doenças Assintomáticas/epidemiologia , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Laboratórios Hospitalares , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , SARS-CoV-2 , Estados Unidos/epidemiologia , Adulto Jovem
4.
MMWR Morb Mortal Wkly Rep ; 69(32): 1081-1088, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32790664

RESUMO

Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.


Assuntos
Infecções por Coronavirus/diagnóstico , Infecções por Coronavirus/terapia , Hospitalização/estatística & dados numéricos , Pneumonia Viral/diagnóstico , Pneumonia Viral/terapia , Adolescente , Betacoronavirus/isolamento & purificação , COVID-19 , Criança , Pré-Escolar , Doença Crônica , Serviços de Laboratório Clínico , Infecções por Coronavirus/epidemiologia , Etnicidade/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Pandemias , Obesidade Infantil/epidemiologia , Pneumonia Viral/epidemiologia , Fatores de Risco , SARS-CoV-2 , Índice de Gravidade de Doença , Estados Unidos/epidemiologia
5.
MMWR Morb Mortal Wkly Rep ; 69(43): 1576-1583, 2020 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-33119554

RESUMO

Health care personnel (HCP) can be exposed to SARS-CoV-2, the virus that causes coronavirus disease 2019 (COVID-19), both within and outside the workplace, increasing their risk for infection. Among 6,760 adults hospitalized during March 1-May 31, 2020, for whom HCP status was determined by the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), 5.9% were HCP. Nursing-related occupations (36.3%) represented the largest proportion of HCP hospitalized with COVID-19. Median age of hospitalized HCP was 49 years, and 89.8% had at least one underlying medical condition, of which obesity was most commonly reported (72.5%). A substantial proportion of HCP with COVID-19 had indicators of severe disease: 27.5% were admitted to an intensive care unit (ICU), 15.8% required invasive mechanical ventilation, and 4.2% died during hospitalization. HCP can have severe COVID-19-associated illness, highlighting the need for continued infection prevention and control in health care settings as well as community mitigation efforts to reduce transmission.


Assuntos
Infecções por Coronavirus/terapia , Pessoal de Saúde/estatística & dados numéricos , Hospitalização/estatística & dados numéricos , Pneumonia Viral/terapia , Adolescente , Adulto , Idoso , COVID-19 , Infecções por Coronavirus/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pandemias , Pneumonia Viral/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
6.
Nucleic Acids Res ; 46(20): 10635-10648, 2018 11 16.
Artigo em Inglês | MEDLINE | ID: mdl-30102404

RESUMO

The piwi interacting RNAs (piRNAs) are small non-coding RNAs that specifically bind to the PIWI proteins, a functional requirement. The piRNAs regulate germline development, transposons control, and gene expression. However, piRNA-mediated post-transcriptional gene regulation in human somatic cells is not well understood. We discovered a human piRNA (piR-FTH1) which has a complementary sequence in the ferritin heavy chain 1 (Fth1) mRNA. We demonstrated that expression of piR-FTH1 and Fth1 are inversely correlated in the tested tumor cell lines. We found that piR-FTH1 negatively regulates the Fth1 expression at post-transcriptional level in triple negative breast cancer (TNBC) cells. Additionally, we confirmed that transfected piR-FTH1 knocks down the Fth1 mRNA via the HIWI2 and HILI mediated mechanism. piR-FTH1 mediated Fth1 repression also increased doxorubicin sensitivity by a remarkable 20-fold in TNBC cells. Since the current piRNA-mediated knockdowns of target mRNA are mostly reported in germ line cells, piRNA-mediated post-transcriptional gene regulation in somatic cells is rather unique in its application and mechanistically uses an alternative pathway to siRNA and miRNA. This work begins to lay the groundwork with a broader impact on treatment of various diseases that are linked to elevated levels of specific mRNAs which have a piRNA target.


Assuntos
Ferritinas/genética , Proteínas/genética , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Transdução de Sinais/genética , Células A549 , Linhagem Celular Tumoral , Ferritinas/metabolismo , Regulação Neoplásica da Expressão Gênica , Células HEK293 , Humanos , Células MCF-7 , Oxirredutases , Proteínas/metabolismo , Proteínas de Ligação a RNA
7.
J Pediatr Orthop ; 40(10): e952-e957, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32796210

RESUMO

BACKGROUND: Increased enrollment in government-based insurance plans has been reported. With youth sports injuries on the rise, increased ordering of advanced imaging such as magnetic resonance imaging (MRI) has occurred. This study sought to report on the impact of insurance type on access to and results of knee MRI in pediatric sports medicine patients. METHODS: A retrospective review of 178 consecutive pediatric sports medicine clinics was completed. INCLUSION CRITERIA: patients younger than 18 years, routine knee MRI ordered, sports medicine diagnosis, and insurance. Data included basic demographics, injury date, date and location (urgent care vs. clinic) of the first presentation, details of MRI ordering and approval, date and location of MRI follow-up, MRI results (negative, minor findings, major findings), and eventual treatment required. RESULTS: A total of 168 charts underwent a complete review. The patients' average age was 14±3 years and 54% (N=90) were female. Ninety-eight had government insurance and 70 had commercial insurance. The time between injury and MRI completion was significantly longer with government insurance (34 vs. 67 d, P<0.01). Government insurance had increased wait time between the first visit and MRI completion (11 vs. 40 d, P<0.001) as well as MRI order and completion (9 vs. 16.5 d, P<0.001). There was no significant difference in positive findings on MRI between insurance groups, including both major and minor findings nor in the proportion receiving eventual operative treatment. CONCLUSION: Pediatric sports medicine patients with government insurance have delays in obtaining knee MRI, despite there being no difference in the rate of positive findings and subsequent operative treatments. LEVEL OF EVIDENCE: Level III-case-control study.


Assuntos
Traumatismos em Atletas/diagnóstico por imagem , Cobertura do Seguro , Traumatismos do Joelho/diagnóstico por imagem , Imageamento por Ressonância Magnética/economia , Adolescente , Estudos de Casos e Controles , Criança , Feminino , Humanos , Seguro , Masculino , Pediatria/economia , Estudos Retrospectivos , Medicina Esportiva/economia
8.
BMC Public Health ; 19(1): 1659, 2019 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-31823751

RESUMO

BACKGROUND: Infectious disease forecasting aims to predict characteristics of both seasonal epidemics and future pandemics. Accurate and timely infectious disease forecasts could aid public health responses by informing key preparation and mitigation efforts. MAIN BODY: For forecasts to be fully integrated into public health decision-making, federal, state, and local officials must understand how forecasts were made, how to interpret forecasts, and how well the forecasts have performed in the past. Since the 2013-14 influenza season, the Influenza Division at the Centers for Disease Control and Prevention (CDC) has hosted collaborative challenges to forecast the timing, intensity, and short-term trajectory of influenza-like illness in the United States. Additional efforts to advance forecasting science have included influenza initiatives focused on state-level and hospitalization forecasts, as well as other infectious diseases. Using CDC influenza forecasting challenges as an example, this paper provides an overview of infectious disease forecasting; applications of forecasting to public health; and current work to develop best practices for forecast methodology, applications, and communication. CONCLUSIONS: These efforts, along with other infectious disease forecasting initiatives, can foster the continued advancement of forecasting science.


Assuntos
Doenças Transmissíveis/epidemiologia , Previsões , Saúde Pública , Centers for Disease Control and Prevention, U.S. , Epidemias , Humanos , Influenza Humana/epidemiologia , Modelos Teóricos , Pandemias , Estações do Ano , Estados Unidos/epidemiologia
9.
Clin Lab ; 64(6): 1097-1100, 2018 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-29945312

RESUMO

BACKGROUND: Our aim was to verify if procalcitonin (PCT) measurements using the new point-of-care testing i-CHROMATM are interchangeable with those of Liaison XL. METHODS: One hundred seventeen serum samples were processed sequentially on a Liaison XL and i-CHROMATM. Statistical analysis was done using the Passing-Bablok regression, Bland-Altman test, and Cohen's Kappa statistic. RESULTS: Proportional and constant differences were observed between i-CHROMATM and Liaison XL. The 95% CI of the mean bias% was very large, exceeding the maximum allowable TE% and the clinical reference change value. However, the concordance between methods at the clinical relevant cutoffs was strong, with the exception of the 0.25 ng/mL cutoff which was moderate. CONCLUSIONS: Our data suggest that i-CHROMATM is not interchangeable with Liaison XL. However, while the strong concordance at the clinical relevant cutoffs allows us to consider i-CHROMATM a suitable option to Liaison XL to support clinicians' decision-making; nevertheless, the moderate agreement at the 0.25 ng/mL cutoff recommends caution in interpreting the data around this cutoff.


Assuntos
Automação Laboratorial/instrumentação , Automação Laboratorial/métodos , Testes Imediatos , Pró-Calcitonina/sangue , Automação Laboratorial/normas , Humanos , Controle de Qualidade , Valores de Referência , Reprodutibilidade dos Testes
10.
S D Med ; 71(5): 224-229, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29999610

RESUMO

BACKGROUND: Amblyopia is a preventable, sight stealing disorder with a prevalence of approximately 2-4 percent in the U.S. pediatric population. Identifying efficacious, early stage screening modalities is of critical importance to sustain quality of vision and quality of life. This project assessed the quality of screening methods used in the Children's Vision Screening Initiative (CVSI), administered by Northern Plains Eye Foundation in collaboration with Western South Dakota Lions Clubs, by comparing to data collected in follow-up appointments at professional eye care clinics. METHODS: Data from 120 cases for children ages 6 months-12 years collected between February 2014 to July 2016 were compared. Only cases that had undergone initial screening by CVSI using a SPOT photoscreener device and that attended a subsequently scheduled eye care professional referral follow-up appointment were evaluated. SPOT screening performance measures on detecting amblyopia risk factors and the accuracy of refractive error data were evaluated. RESULTS: Review of professional evaluations showed that 23 percent of cases referred by SPOT screening had detectable amblyopia and 82 percent of all cases referred were found to be in need of further therapy as a result of examination findings. The SPOT device showed fair sensitivity and good specificity in the detection of astigmatism (76 percent/86 percent), strabismus (50 percent/96 percent), and anisometropia (75 percent/90 percent). CONCLUSION: Vision screening performed using the SPOT device represents a valuable modality that is easily employable and can provide tremendous benefit to children in the state of South Dakota.


Assuntos
Ambliopia/diagnóstico , Seleção Visual , Humanos , Lactente , Qualidade de Vida , Fatores de Risco , Sensibilidade e Especificidade , South Dakota
11.
Curr Genet ; 63(2): 281-292, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-27491680

RESUMO

Adaptation by natural selection might improve the fitness of an organism and its probability to survive in unfavorable environmental conditions. Decoding the genetic basis of adaptive evolution is one of the great challenges to deal with. To this purpose, Saccharomyces cerevisiae has been largely investigated because of its short division time, excellent aneuploidy tolerance and the availability of the complete sequence of its genome with a thorough genome database. In the past, we developed a system, named bridge-induced translocation, to trigger specific, non-reciprocal translocations, exploiting the endogenous recombination system of budding yeast. This technique allows users to generate a heterogeneous population of cells with different aneuploidies and increased phenotypic variation. In this work, we demonstrate that ad hoc chromosomal translocations might induce adaptation, fostering selection of thermo-tolerant yeast strains with improved phenotypic fitness. This "yeast eugenomics" correlates with a shift to enhanced expression of genes involved in stress response, heat shock as well as carbohydrate metabolism. We propose that the bridge-induced translocation is a suitable approach to generate adapted, physiologically boosted strains for biotechnological applications.


Assuntos
Adaptação Fisiológica/genética , Evolução Molecular , Regulação Fúngica da Expressão Gênica/genética , Saccharomyces cerevisiae/genética , Seleção Genética , Translocação Genética , Cromossomos Fúngicos/genética , Dano ao DNA , Reparo do DNA , DNA Fúngico/genética , DNA Fúngico/metabolismo , Aptidão Genética , Proteínas de Choque Térmico/genética , Proteínas de Choque Térmico/metabolismo , Resposta ao Choque Térmico/genética , Modelos Genéticos , Fenótipo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Temperatura , Fatores de Tempo
12.
Mol Genet Genomics ; 291(1): 423-35, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26423068

RESUMO

Chromosome translocation is a major genomic event for a cell, affecting almost every of its life aspects ranging from metabolism, organelle maintenance and homeostasis to gene maintenance and expression. By using the bridge-induced translocation system, we defined the effects of induced chromosome translocation on the chronological life span (CLS) of yeast with particular interest to the oxidative stress condition. The results demonstrate that every translocant strain has a different CLS, but all have a high increase in reactive oxygen species and in lipid peroxides levels at the end of the life span. This could be due to the very unique and strong deregulation of the oxidative stress network. Furthermore, the loss of the translocated chromosome occurs at the end of the life span and is locus dependent. Additionally, the RDH54 gene may play a role in the correct segregation of the translocant chromosome, since in its absence there is an increase in loss of the bridge-induced translocated chromosome.


Assuntos
Longevidade/genética , Espécies Reativas de Oxigênio/metabolismo , Leveduras/genética , Leveduras/metabolismo , Proteínas Fúngicas/genética , Peróxidos Lipídicos/metabolismo , Estresse Oxidativo/genética , Translocação Genética/genética
13.
J Neurophysiol ; 110(1): 42-54, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-23576706

RESUMO

Large cell motoneurons in the Cancer borealis cardiac ganglion generate rhythmic bursts of action potentials responsible for cardiac contractions. While it is well known that these burst potentials are dependent on coordinated interactions among depolarizing and hyperpolarizing conductances, the depolarizing currents present in these cells, and their biophysical characteristics, have not been thoroughly described. In this study we used a combined molecular biology and electrophysiology approach to look at channel identity, expression, localization, and biophysical properties for two distinct high-voltage-activated calcium currents present in these cells: a slow calcium current (ICaS) and a transient calcium current (ICaT). Our data indicate that CbCaV1 is a putative voltage-gated calcium channel subunit in part responsible for an L-type current, while CbCaV2 (formerly cacophony) is a subunit in part responsible for a P/Q-type current. These channels appear to be localized primarily to the somata of the motoneurons. A third calcium channel gene (CbCaV3) was identified that encodes a putative T-type calcium channel subunit and is expressed in these cells, but electrophysiological studies failed to detect this current in motoneuron somata. In addition, we identify and characterize for the first time in these cells a calcium-activated nonselective cationic current (ICAN), as well as a largely noninactivating TTX-sensitive current reminiscent of a persistent sodium current. The identification and further characterization of these currents allow both biological and modeling studies to move forward with more attention to the complexity of interactions among these distinct components underlying generation of bursting output in motoneurons.


Assuntos
Canais de Cálcio/fisiologia , Gânglios dos Invertebrados/fisiologia , Neurônios Motores/fisiologia , Potenciais de Ação , Animais , Braquiúros , Coração/inervação
14.
J Child Psychol Psychiatry ; 54(5): 527-35, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22676856

RESUMO

BACKGROUND: Attention deficit hyperactivity disorder is increased in children with intellectual disability. Previous research has suggested stimulants are less effective than in typically developing children but no studies have titrated medication for individual optimal dosing or tested the effects for longer than 4 weeks. METHOD: One hundred and twenty two drug-free children aged 7-15 with hyperkinetic disorder and IQ 30-69 were recruited to a double-blind, placebo-controlled trial that randomized participants using minimization by probability, stratified by referral source and IQ level in a one to one ratio. Methylphenidate was compared with placebo. Dose titration comprised at least 1 week each of low (0.5 mg/kg/day), medium (1.0 mg/kg/day) and high dose (1.5 mg/kg/day). Parent and teacher Attention deficit hyperactivity disorder (ADHD) index of the Conners Rating Scale-Short Version at 16 weeks provided the primary outcome measures. Clinical response was determined with the Clinical Global Impressions scale (CGI-I). Adverse effects were evaluated by a parent-rated questionnaire, weight, pulse and blood pressure. Analyses were by intention to treat. TRIAL REGISTRATION: ISRCTN 68384912. RESULTS: Methylphenidate was superior to placebo with effect sizes of 0.39 [95% confidence intervals (CIs) 0.09, 0.70] and 0.52 (95% CIs 0.23, 0.82) for the parent and teacher Conners ADHD index. Four (7%) children on placebo versus 24 (40%) of those on methylphenidate were judged improved or much improved on the CGI. IQ and autistic symptoms did not affect treatment efficacy. Active medication was associated with sleep difficulty, loss of appetite and weight loss but there were no significant differences in pulse or blood pressure. CONCLUSIONS: Optimal dosing of methylphenidate is practical and effective in some children with hyperkinetic disorder and intellectual disability. Adverse effects typical of methylphenidate were seen and medication use may require close monitoring in this vulnerable group.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Deficiência Intelectual/diagnóstico , Deficiência Intelectual/tratamento farmacológico , Metilfenidato/administração & dosagem , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Comorbidade , Relação Dose-Resposta a Droga , Método Duplo-Cego , Inglaterra , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Deficiência Intelectual/psicologia , Masculino , Metilfenidato/efeitos adversos , Determinação da Personalidade
15.
Cell Chem Biol ; 30(3): 308-320.e5, 2023 03 16.
Artigo em Inglês | MEDLINE | ID: mdl-36882060

RESUMO

RNA oxidation has been implicated in neurodegeneration, but the underlying mechanism for such effects is unclear. Extensive RNA oxidation occurs within the neurons in multiple sclerosis (MS) brains. Here, we identified selectively oxidized mRNAs in neuronal cells that pertained to neuropathological pathways. N-acetyl aspartate transferase 8 like (NAT8L) is one such transcript, whose translation product enzymatically synthesizes N-acetyl aspartic acid (NAA), a neuronal metabolite important for myelin synthesis. We reasoned that impediment of translation of an oxidized NAT8L mRNA will result in a reduction in its cognate protein, thus lowering the NAA level. This hypothesis is supported by our studies on cells, an animal model, and postmortem human MS brain. Reduced brain NAA level hampers myelin integrity making neuronal axons more susceptible to damage, which contributes to MS neurodegeneration. Overall, this work provides a framework for a mechanistic understanding of the link between RNA oxidation and neurodegeneration.


Assuntos
Esclerose Múltipla , Animais , Humanos , Esclerose Múltipla/metabolismo , Esclerose Múltipla/patologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Neurônios/metabolismo , Encéfalo/metabolismo , RNA/metabolismo , Acetiltransferases/metabolismo
16.
ACS Chem Biol ; 17(7): 1723-1732, 2022 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-35687865

RESUMO

Piwi-interacting RNAs (piRNAs) are a group of small noncoding RNA molecules that regulate the activity of transposons and control gene expression. The cellular concentration of RNAs is generally maintained by their rates of biogenesis and degradation. Although the biogenesis pathways of piRNAs have been well defined, their degradation mechanism is still unknown. Here, we show that degradation of human piRNAs is mostly dependent on the 5'-3' exoribonuclease pathway. The presence of 3'-end 2'-O-methylation in piRNAs significantly reduced their degradation through the exosome-mediated decay pathway. The accumulation of piRNAs in XRN1 and XRN2 exoribonuclease-depleted cells further supports the 5'-3' exoribonuclease-mediated decay of piRNAs. Moreover, formation of stable secondary structures in piRNAs slows the rate of XRN1-mediated degradation. Our findings establish a framework for the piRNA degradation mechanism in cells and thus provide crucial information about how the basal level concentration of piRNAs is maintained in cells.


Assuntos
Exorribonucleases , Estabilidade de RNA , RNA Interferente Pequeno , Proteínas Argonautas/metabolismo , Exorribonucleases/metabolismo , Humanos , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo
17.
Neuronal Signal ; 6(1): NS20210054, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35449591

RESUMO

Down syndrome (DS) is the most common chromosomal abnormality and leads to intellectual disability, increased risk of cardiac defects, and an altered immune response. Individuals with DS have an extra full or partial copy of chromosome 21 (trisomy 21) and are more likely to develop early-onset Alzheimer's disease (AD) than the general population. Changes in expression of human chromosome 21 (Hsa21)-encoded genes, such as amyloid precursor protein (APP), play an important role in the pathogenesis of AD in DS (DS-AD). However, the mechanisms of DS-AD remain poorly understood. To date, several mouse models with an extra copy of genes syntenic to Hsa21 have been developed to characterise DS-AD-related phenotypes. Nonetheless, due to genetic and physiological differences between mouse and human, mouse models cannot faithfully recapitulate all features of DS-AD. Cells differentiated from human-induced pluripotent stem cells (iPSCs), isolated from individuals with genetic diseases, can be used to model disease-related cellular and molecular pathologies, including DS. In this review, we will discuss the limitations of mouse models of DS and how these can be addressed using recent advancements in modelling DS using human iPSCs and iPSC-mouse chimeras, and potential applications of iPSCs in preclinical studies for DS-AD.

18.
Orthop J Sports Med ; 10(6): 23259671221100223, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35668871

RESUMO

Background: Isolated pediatric lateral ankle injuries, including ankle sprain (AS) and nondisplaced Salter-Harris type 1 (SH-1) distal fibular fracture, are common orthopaedic sports-related injuries. Variability in treatment is suspected among pediatric orthopaedic surgeons. Complications from medical treatment or lack thereof have not been reported in this population. Purpose: The purpose of this study was to investigate treatment variability and associated complications after pediatric AS and SH-1 via a survey of members of the Pediatric Orthopaedic Society of North American (POSNA). Study Design: Cross-sectional study. Level of evidence, 5. Methods: A voluntary, anonymous survey was distributed to POSNA membership (approximately 1400 members) via email. Survey questions, specific to both grade 1 or 2 AS and nondisplaced or minimally displaced SH-1 injuries in skeletally immature patients, focused on initial evaluation, immobilization, return to sports, and complications. We analyzed variability both in treatment between AS and SH-1 injury and in respondent characteristics. For statistical analysis, chi-square or Fisher exact test was used for categorical variables, and analysis of variance was used for continuous variables. Results: The survey response rate was 16.4% (229/1400). Of the respondents, 27.7% used examination only to distinguish between AS and SH-1, whereas 18.7% performed serial radiography to aid with diagnosis. A controlled ankle motion boot or walking boot was the most common immobilization technique for both AS (46.3%) and SH-1 (55.6%); the second most common technique was bracing in AS (33.5%) and casting in SH-1 (34.7%). Approximately one-third of all respondents recommended either outpatient or home physical therapy for AS, whereas only 11.4% recommended physical therapy for SH-1 (P < .01). Results showed that 81.2% of respondents reported no complications for SH-1 treatment and 87.8% reported no complications for AS treatment. Cast complications were reported by 9.6% for SH-1 and 5.2% for AS. Rare SH-1 complications included distal fibular growth arrest, infection, nonunion, late fracture displacement, and recurrent fracture. Conclusion: Significant variability was found in primary treatment of pediatric AS and SH-1 injuries. Rare complications from injury, treatment, and neglected treatment after SH-1 and AS were reported.

19.
J Clin Med ; 11(22)2022 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-36431268

RESUMO

BACKGROUND: Inhaled bronchodilators are frequently used among patients with primary ciliary dyskinesia (PCD), although neither the effectiveness nor the prevalence of their use is known, due to the paucity of relevant studies. METHODS: This is a retrospective analysis of pre- and post-bronchodilator spirometry results, of patients with PCD from two centers. Correlations were examined of bronchodilator response, with asthma and atopy markers. RESULTS: Of 115 patients, 46 (40%) completed spirometry pre- and post-bronchodilation. Of these, 26 (56.5%) demonstrated reversible airway obstruction (increase in %FEV1 predicted ≥ 10%). Obstruction reversibility was not found to be associated with a family history of asthma, blood eosinophil level, elevated IgE, or atopy symptoms. Of the 46 patients who completed bronchodilator spirometry, 29 (63%) were regularly using bronchodilators and inhaled corticosteroids. CONCLUSIONS: More than half of patients with PCD presented with reversible airway obstruction, without any correlation to markers of personal or familial atopy. Inhaled bronchodilators and corticosteroid therapies are commonly used for treating PCD. Evaluating bronchodilator response should be considered, and its effectiveness should be further studied.

20.
PLoS One ; 17(9): e0261800, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36149842

RESUMO

Biologging tags are a key enabling tool for investigating cetacean behavior and locomotion in their natural habitat. Identifying and then parameterizing gait from movement sensor data is critical for these investigations, but how best to characterize gait from tag data remains an open question. Further, the location and orientation of a tag on an animal in the field are variable and can change multiple times during a deployment. As a result, the relative orientation of the tag with respect to (wrt) the animal must be determined for analysis. Currently, custom scripts that involve species-specific heuristics tend to be used in the literature. These methods require a level of knowledge and experience that can affect the reliability and repeatability of the analysis. Swimming gait is composed of a sequence of body poses that have a specific spatial pattern, and tag-based measurements of this pattern can be utilized to determine the relative orientation of the tag. This work presents an automated data processing pipeline (and software) that takes advantage of these patterns to 1) Identify relative motion between the tag and animal; 2) Estimate the relative orientation of the tag wrt the animal using a data-driven approach; and 3) Calculate gait parameters that are stable and invariant to animal pose. Validation results from bottlenose dolphin tag data show that the average relative orientation error (tag wrt the body) after processing was within 11 degrees in roll, pitch, and yaw directions. The average precision and recall for detecting instances of relative motion in the dolphin data were 0.87 and 0.89, respectively. Tag data from humpback and beluga whales were then used to demonstrate how the gait analysis can be used to enhance tag-based investigations of movement and behavior. The MATLAB source code and data presented in the paper are publicly available (https://github.com/ding-z/cetacean-pose-gait-analysis.git), along with suggested best practices.


Assuntos
Golfinho Nariz-de-Garrafa , Análise da Marcha , Animais , Fenômenos Biomecânicos , Marcha , Locomoção , Reprodutibilidade dos Testes
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