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1.
JAMA Intern Med ; 2024 Apr 08.
Artigo em Inglês | MEDLINE | ID: mdl-38587827

RESUMO

Importance: Alcohol use is prevalent among university students. Mobile instant messaging apps could enhance the effectiveness of an alcohol brief intervention (ABI), but the evidence is scarce. Objective: To evaluate the effectiveness of an ABI plus 3 months of mobile chat-based instant messaging support for alcohol reduction in university students at risk of alcohol use disorder. Design, Setting, and Participants: In this randomized clinical trial, 772 students at risk of alcohol use disorder (Alcohol Use Disorders Identification Test [AUDIT] score ≥8) were recruited from 8 universities in Hong Kong between October 15, 2020, and May 12, 2022. Participants were randomly assigned 1:1 to either the intervention or control group. Interventions: Both groups received the same ABI at baseline, which consisted of face-to-face or video conferencing with research nurses who delivered personalized feedback based on the participant's AUDIT risk level, along with a 12-page booklet describing the benefits of alcohol reduction and the harmful effects of alcohol on health and social well-being. The intervention group then received 3 months of chat-based instant messaging support on alcohol reduction guided by behavioral change techniques. The control group received 3 months of short message service (SMS) messaging on general health topics. Main Outcomes and Measures: All outcomes were self-reported. The primary outcome was alcohol consumption in grams per week at 6 months of follow-up. By definition, 1 alcohol unit contains 10 g of pure alcohol. Secondary outcomes at the 6-month follow-up included changes in AUDIT score, weekly alcohol consumption, intention to drink in the next 30 days, drinking frequency and any binge or heavy drinking in the past 30 days, and self-efficacy of quitting drinking. The primary analysis followed the intention-to-treat principle, and linear regression (reported as unstandardized coefficient B) and logistic regression (reported as odds ratios) were used to compare the primary and secondary outcomes between the intervention and control groups. Results: The study included 772 students (mean [SD] age, 21.1 [3.5] years; 395 females [51.2%]) who were randomly assigned to either the intervention (n = 386) or control (n = 386) group. In the intention-to-treat analysis, the intervention group had lower alcohol consumption in grams per week (B, -11.42 g [95% CI, -19.22 to -3.62 g]; P = .004), a lower AUDIT score (B, -1.19 [95% CI, -1.63 to -0.34]; P = .003), reduced weekly alcohol unit consumption (B, -1.14 [95% CI, -1.92 to -0.36]; P = .004), and less intention to drink (odds ratio, 0.66 [95% CI, 0.47 to 0.92]; P = .01) at the 6-month follow-up compared with the control group. In analyses adjusted for baseline characteristics, interacting at least once with the research nurse on the instant messaging application resulted in lower estimated alcohol consumption in grams per week (adjusted B, -17.87 g [95% CI, -32.55 to -3.20 g]; P = .01), lower weekly alcohol unit consumption (adjusted B, -1.79 [95% CI, -3.25 to -0.32]; P = .02), and a lower AUDIT score (adjusted B, -0.53 [95% CI, -1.87 to -0.44]; P = .01) at 6 months. Conclusions and Relevance: Results of this randomized clinical trial indicate that mobile chat-based instant messaging support for alcohol reduction in addition to an ABI was effective in reducing alcohol consumption in university students in Hong Kong at risk of alcohol use disorder. Trial Registration: ClinicalTrials.gov Identifier: NCT04025151.

2.
Sci Rep ; 14(1): 8747, 2024 04 16.
Artigo em Inglês | MEDLINE | ID: mdl-38627483

RESUMO

This study aimed to evaluate the incidence and likelihood of antibiotic-associated encephalopathy (AAE), comparing rates among the classes of antibiotics in monotherapy or in combination therapy. We also investigated the associations between the incidence of AAE and the glomerular filtration rate (GFR) and electroencephalogram features. Consecutive admissions that used any kind of antibiotics to treat infectious diseases were identified from six hospitals. We classified antibiotics according to three distinct pathophysiologic mechanisms and clinical subtypes. We searched for the incidence of AAE as the primary outcome. A total of 97,433 admission cases among 56,038 patients was identified. Cases that received type 1 antibiotics had significantly more frequent AAE compared to those that received type 2 antibiotics (adjusted odds ratio [OR], 2.62; 95% confidence interval [CI] 1.15-5.95; P = 0.021). Combined use of type 1 + 2 antibiotics was associated with a significantly higher incidence of AAE compared to the use of type 2 antibiotics alone (adjusted OR, 3.44; 95% CI 1.49-7.93; P = 0.004). Groups with GFR < 60 mL/min/1.73 m2 had significantly higher incidence rates of AAE compared to those with GFRs ≥ 90 mL/min/1.73 m2 among cases that received type 1 + 2 antibiotics. Detection of spike-and-wave or sharp-and-wave patterns on electroencephalogram was significantly more common in the combination therapy group. Combination use of antibiotics was associated with a higher incidence of AAE compared to monotherapy. The incidence of AAE significantly increased as renal function decreased, and epileptiform discharges were more likely to be detected in cases receiving combined antibiotics.


Assuntos
Antibacterianos , Encefalopatias , Humanos , Antibacterianos/efeitos adversos , Incidência , Taxa de Filtração Glomerular , Encefalopatias/induzido quimicamente , Encefalopatias/epidemiologia , Encefalopatias/tratamento farmacológico , Hospitais
3.
Artigo em Inglês | MEDLINE | ID: mdl-38636591

RESUMO

Evidence is mounting that climate change is having a significant impact on exacerbations of rhinitis. Concomitantly, the prevalence of allergic rhinitis is increasing at an accelerated rate. We herein explore the impact of carbon dioxide, barometric pressure and humidity changes, and anthropogenic pollutants on aeroallergens and rhinitis hypersensitivity. Important immune mechanisms underlying the climate-driven effects on rhinitis are discussed. Also, climate change is shifting ecological zones and seasons, increasing weather extremes, and altering regional atmospheric and environmental conditions. The direct impact of these factors on promoting allergic and nonallergic rhinitis is reviewed.

4.
Curr Opin Allergy Clin Immunol ; 24(3): 109-113, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38547381

RESUMO

PURPOSE OF REVIEW: The purpose of this study is to understand the approach to precision medicine and personalized medicine in the management of allergic airway disease. RECENT FINDINGS: Identification of biomarkers as key tools used in precision medicine has led to the development of multiple biologic drugs being used as new treatments for allergic airway disease. SUMMARY: In addition to these advances, there is still much needed effort to improve the feasibility and utility of integrating biologic omics data of precision medicine with physicochemical, behavioral, psychological, and social data to deliver optimized treatments that is personalized for each individual.


Assuntos
Medicina de Precisão , Humanos , Asma/genética , Asma/imunologia , Asma/tratamento farmacológico , Asma/diagnóstico , Asma/terapia , Biomarcadores , Medicina de Precisão/métodos
5.
Otolaryngol Head Neck Surg ; 170(3): 635-667, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38408153

RESUMO

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The guideline development group made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitization, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The guideline development group offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.


Assuntos
Anafilaxia , Asma , Rinite Alérgica , Humanos , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia , Dessensibilização Imunológica , Alérgenos
6.
Otolaryngol Head Neck Surg ; 170 Suppl 1: S1-S42, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38408152

RESUMO

OBJECTIVE: Allergen immunotherapy (AIT) is the therapeutic exposure to an allergen or allergens selected by clinical assessment and allergy testing to decrease allergic symptoms and induce immunologic tolerance. Inhalant AIT is administered to millions of patients for allergic rhinitis (AR) and allergic asthma (AA) and is most commonly delivered as subcutaneous immunotherapy (SCIT) or sublingual immunotherapy (SLIT). Despite its widespread use, there is variability in the initiation and delivery of safe and effective immunotherapy, and there are opportunities for evidence-based recommendations for improved patient care. PURPOSE: The purpose of this clinical practice guideline (CPG) is to identify quality improvement opportunities and provide clinicians trustworthy, evidence-based recommendations regarding the management of inhaled allergies with immunotherapy. Specific goals of the guideline are to optimize patient care, promote safe and effective therapy, reduce unjustified variations in care, and reduce the risk of harm. The target patients for the guideline are any individuals aged 5 years and older with AR, with or without AA, who are either candidates for immunotherapy or treated with immunotherapy for their inhalant allergies. The target audience is all clinicians involved in the administration of immunotherapy. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group (GDG). It is not intended to be a comprehensive, general guide regarding the management of inhaled allergies with immunotherapy. The statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The GDG made a strong recommendation that (Key Action Statement [KAS] 10) the clinician performing allergy skin testing or administering AIT must be able to diagnose and manage anaphylaxis. The GDG made recommendations for the following KASs: (KAS 1) Clinicians should offer or refer to a clinician who can offer immunotherapy for patients with AR with or without AA if their patients' symptoms are inadequately controlled with medical therapy, allergen avoidance, or both, or have a preference for immunomodulation. (KAS 2A) Clinicians should not initiate AIT for patients who are pregnant, have uncontrolled asthma, or are unable to tolerate injectable epinephrine. (KAS 3) Clinicians should evaluate the patient or refer the patient to a clinician who can evaluate for signs and symptoms of asthma before initiating AIT and for signs and symptoms of uncontrolled asthma before administering subsequent AIT. (KAS 4) Clinicians should educate patients who are immunotherapy candidates regarding the differences between SCIT and SLIT (aqueous and tablet) including risks, benefits, convenience, and costs. (KAS 5) Clinicians should educate patients about the potential benefits of AIT in (1) preventing new allergen sensitizations, (2) reducing the risk of developing AA, and (3) altering the natural history of the disease with continued benefit after discontinuation of therapy. (KAS 6) Clinicians who administer SLIT to patients with seasonal AR should offer pre- and co-seasonal immunotherapy. (KAS 7) Clinicians prescribing AIT should limit treatment to only those clinically relevant allergens that correlate with the patient's history and are confirmed by testing. (KAS 9) Clinicians administering AIT should continue escalation or maintenance dosing when patients have local reactions (LRs) to AIT. (KAS 11) Clinicians should avoid repeat allergy testing as an assessment of the efficacy of ongoing AIT unless there is a change in environmental exposures or a loss of control of symptoms. (KAS 12) For patients who are experiencing symptomatic control from AIT, clinicians should treat for a minimum duration of 3 years, with ongoing treatment duration based on patient response to treatment. The GDG offered the following KASs as options: (KAS 2B) Clinicians may choose not to initiate AIT for patients who use concomitant beta-blockers, have a history of anaphylaxis, have systemic immunosuppression, or have eosinophilic esophagitis (SLIT only). (KAS 8) Clinicians may treat polysensitized patients with a limited number of allergens.


Assuntos
Anafilaxia , Asma , Rinite Alérgica , Humanos , Alérgenos , Dessensibilização Imunológica , Rinite Alérgica/diagnóstico , Rinite Alérgica/terapia
7.
J Korean Med Sci ; 39(5): e48, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38317448

RESUMO

Guillain-Barré syndrome (GBS) is an autoimmune-driven condition characterized by acute polyneuropathy, often emerging as a sequel to prior infections or vaccinations. This study presents the first reported cases of GBS emerging after the full recovery from coronavirus disease 2019 (COVID-19) infection in Korea. Despite experiencing mild acute COVID-19 symptoms, these patients faced substantial weakness attributed to GBS, significantly affecting their daily lives. The timely administration of intravenous immunoglobulin treatment halted the progression of symptoms, underscoring the critical importance of early intervention. These cases highlight the potential for neurological complications associated with COVID-19 and underscore the necessity for continuous monitoring and timely medical care.


Assuntos
COVID-19 , Síndrome de Guillain-Barré , Humanos , COVID-19/complicações , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/etiologia , Síndrome de Guillain-Barré/terapia , SARS-CoV-2 , Imunoglobulinas Intravenosas/uso terapêutico , República da Coreia
8.
Int J Equity Health ; 23(1): 8, 2024 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-38233876

RESUMO

BACKGROUND: Female migrant domestic workers (MDW), approximately 8.5 million globally, often live in their employer's home under vulnerable conditions. In Hong Kong, MDWs currently comprise 5% of the population. This study was conducted to assess the association between employment conditions and mental health, and the mediating roles stress and job satisfaction have, among female MDWs in Hong Kong. METHODS: Participants completed an online cross-sectional survey. A total of 1,965 survey were collected between August 2020 and August 2021. Questions in the survey were related to MDWs background information, employment conditions, stress, job satisfaction, and two mental health outcomes: anxiety and depression. An employment conditions score was created to assess the cumulative effect poor employment conditions had on mental health. A multicategorical parallel mediation analysis was used to assess the direct effect employment conditions have on mental health and the indirect effects through stress and job satisfaction. RESULTS: Overall, 17.7% of MDWs were reported to be suffering from anxiety and 30.8% from depression. An increase in poor employment conditions was statistically associated with an increase in both outcomes, while stress levels and job satisfaction mediated this association. CONCLUSIONS: The findings call for increased scrutiny of employment conditions and mental well-being of MDWs.


Assuntos
Saúde Mental , Migrantes , Humanos , Feminino , Hong Kong/epidemiologia , Estudos Transversais , Análise de Mediação , Emprego/psicologia
9.
Drug Alcohol Rev ; 43(1): 233-244, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37565305

RESUMO

INTRODUCTION: Drinking expectancies, the perceived consequences of alcohol consumption, are noted to predict drinking behaviours. However, there is comparatively little research of drinking expectancies in non-Western populations. This study aimed to develop and validate a Chinese Drinking Expectancy Questionnaire (CDEQ-Adult) for Chinese young adults. METHODS: Face and content validity were first assessed of items generated from literature review and previously conducted focus groups. Exploratory (EFA) and confirmatory factor analyses (CFA) were conducted with split-half samples from a random telephone survey that was conducted on Hong Kong Chinese adults between the ages of 18-34 (n = 675). The instrument's convergent validity and internal reliability were also examined. RESULTS: The preliminary instrument items showed good content validity (Item Content Validity Index range: 0.8-1.0). The EFA yielded a 31-item, five-factor model consisting of five domains: Negative Consequences, Interpersonal Benefits, Increased Confidence, Health Benefits and Tension/Stress Reduction (variance explained 63.7%). The CFA revealed that the fit indices for the five-factor model using diagonal weighted least squares estimator were χ2 (256, N = 338) = 394.04, p < 0.001, comparative fit index 0.97, SRMR 0.07, RMSEA 0.06 (95% confidence interval 0.06, 0.08), suggesting a good fit of the model. The Cronbach's α coefficients were 0.94, 0.90, 0.86, 0.77 and 0.57, respectively for each of the five domains (n = 675). Significant associations with past month drinking behaviours and future drinking intentions give strong support for convergent validity. DISCUSSION AND CONCLUSIONS: The CDEQ-Adult is a culturally relevant instrument for assessing drinking expectancies in Chinese young adults for use in future studies.


Assuntos
Reprodutibilidade dos Testes , Humanos , Adulto Jovem , Adolescente , Adulto , Hong Kong , Inquéritos e Questionários , Psicometria , Análise Fatorial
10.
Am J Epidemiol ; 193(2): 296-307, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-37814392

RESUMO

Body mass index (BMI; weight (kg)/height (m)2) is commonly used to measure general adiposity. However, evidence of its appropriateness for males and females remains inconsistent. We aimed to identify the most appropriate sex-specific power value that height should be raised to in the formula and the value that would make it achieve height independency and body fatness dependency. We randomly assigned UK Biobank participants recruited in the United Kingdom between 2006 and 2010 (n = 489,873; mean age = 56.5 years; 94.2% White) to training and testing sets (80%:20%). Using height raised to the power of -50.00 to 50.00, we identified the optimal power value that either minimized correlation with height or maximized correlation with body fat percentage, using age-adjusted correlations. The optimal power values for height were 1.77 for males and 1.39 for females. The new formulas resulted in 4.5% of females and 2.4% of males being reclassified into a different BMI category. The formulas did not show significant improvement (in terms of area under the receiver operating characteristic curve, sensitivity, and specificity) in identifying individuals with excessive body fat percentage or in predicting risk of all-cause mortality. Therefore, the conventional BMI formula is still valuable in research and disease screening for both sexes.


Assuntos
Bancos de Espécimes Biológicos , Biobanco do Reino Unido , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Massa Corporal , Peso Corporal , Tecido Adiposo , Adiposidade , Estatura
11.
Otolaryngol Clin North Am ; 57(2): 309-317, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37923592

RESUMO

There is mounting evidence that climate change is having a significant influence on exacerbations of airway disease. We herein explore the physical factors of carbon dioxide, temperature increases, and humidity on intensifying allergen and fungal growth, and worsening air quality. The direct influence of these factors on promoting allergic rhinitis, chronic rhinosinusitis, and allergic fungal rhinosinusitis is reviewed.


Assuntos
Rinite Alérgica , Sinusite , Humanos , Mudança Climática , Nariz , Alérgenos
12.
Stem Cell Res ; 74: 103292, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38154383

RESUMO

MECP2 Duplication Syndrome (MDS) is a rare, severe neurodevelopmental disorder arising from duplications in the Xq28 region containing the MECP2 gene that predominantly affects males. We generated five human induced pluripotent stem cell (iPSC) lines from the fibroblasts of individuals carrying between 0.355 and 11.2 Mb size duplications in the chromosomal locus containing MECP2. All lines underwent extensive testing to confirm MECP2 duplication and iPSC-related features such as morphology, pluripotency markers, and trilineage differentiation potential. These lines are a valuable resource for molecular and functional studies of MDS as well as screening for a variety of therapeutic approaches.


Assuntos
Células-Tronco Pluripotentes Induzidas , Deficiência Intelectual Ligada ao Cromossomo X , Proteína 2 de Ligação a Metil-CpG , Humanos , Masculino , Diferenciação Celular , Duplicação Gênica , Deficiência Intelectual Ligada ao Cromossomo X/genética , Proteína 2 de Ligação a Metil-CpG/genética
13.
Health Policy ; 138: 104920, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37797444

RESUMO

To counter the harms of excessive alcohol use, the World Health Organization (WHO) outlined a series of alcohol policy recommendations, including the most cost-effective "Best Buys". This study aims to obtain key stakeholder views on feasibility of implementing various publicly endorsed alcohol policies in Hong Kong, a relatively low alcohol consumption region with few extant alcohol regulations. Between 2019 and 2021, we conducted semi-structured interviews with stakeholders involved in alcohol policy adoption and implementation. Interviewees included hospitality/alcohol sales workers (n = 13) and government officers (n = 4). The stakeholders noted that although WHO advocacy facilitated local policy considerations, the adoption of stringent measures was challenged by low political priority due to the low visibility of harms. For implementing strategies, the stakeholders cited alignment with social norms as a major facilitator, whereas law enforcement difficulties and resistance from industry/business sectors were viewed as major obstacles. There was a general belief that population-level alcohol policies would be effective for certain groups of drinkers but would also harm the local economy and detract from Hong Kong's image as a "world city". Hong Kong may not be ready to adopt a wide range of highly restrictive population-level alcohol policies. Local governments should carefully consider contextual factors when following international recommendations.


Assuntos
Consumo de Bebidas Alcoólicas , Política Pública , Humanos , Hong Kong , Estudos de Viabilidade , Consumo de Bebidas Alcoólicas/prevenção & controle , Governo
14.
Genes Dev ; 37(19-20): 883-900, 2023 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-37890975

RESUMO

Loss-of-function mutations in MECP2 cause Rett syndrome (RTT), a severe neurological disorder that mainly affects girls. Mutations in MECP2 do occur in males occasionally and typically cause severe encephalopathy and premature lethality. Recently, we identified a missense mutation (c.353G>A, p.Gly118Glu [G118E]), which has never been seen before in MECP2, in a young boy who suffered from progressive motor dysfunction and developmental delay. To determine whether this variant caused the clinical symptoms and study its functional consequences, we established two disease models, including human neurons from patient-derived iPSCs and a knock-in mouse line. G118E mutation partially reduces MeCP2 abundance and its DNA binding, and G118E mice manifest RTT-like symptoms seen in the patient, affirming the pathogenicity of this mutation. Using live-cell and single-molecule imaging, we found that G118E mutation alters MeCP2's chromatin interaction properties in live neurons independently of its effect on protein levels. Here we report the generation and characterization of RTT models of a male hypomorphic variant and reveal new insight into the mechanism by which this pathological mutation affects MeCP2's chromatin dynamics. Our ability to quantify protein dynamics in disease models lays the foundation for harnessing high-resolution single-molecule imaging as the next frontier for developing innovative therapies for RTT and other diseases.


Assuntos
Cromatina , Síndrome de Rett , Feminino , Humanos , Masculino , Camundongos , Animais , Cromatina/metabolismo , Encéfalo/metabolismo , Proteína 2 de Ligação a Metil-CpG/genética , Síndrome de Rett/genética , Mutação , Neurônios/metabolismo
15.
BJOG ; 130 Suppl 3: 43-52, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37671586

RESUMO

OBJECTIVE: To examine inflammatory lesions in placentas of stillbirths, preterm neonatal deaths and term controls in India and Pakistan. DESIGN: Prospective, observational study. SETTING: Three hospitals in India and a large maternity hospital in Pakistan. POPULATION: The enrolled participants with placentas available for histology evaluation included stillbirths (n = 814), preterm live births who died within 28 days of birth (n = 618) and term live birth controls (n = 201). From this same population, polymerase chain reaction (PCR) analysis for pathogens was performed on 809 stillbirth placentas, 614 neonatal death placentas and the placentas of 201 term controls. Placentas from preterm infants who lived beyond day 28 (n = 1432) were only available from India. METHODS: A prospective observational study of placental inflammatory lesions defined by the Amsterdam criteria and on the same placentas, multiplex PCR evaluation for 75 pathogens using TaqMan Array Cards. MAIN OUTCOME MEASURES: Any placental inflammatory lesions, including chorioamnionitis, funisitis, villitis and intervillitis and their association with various pathogens. RESULTS: In the Indian liveborn preterm infants, placental inflammation of any kind was present in 26.2% of those who died versus 16.6% of those who lived (p = 0.0002). Chorioamnionitis was present in 25.8% of those who died versus 16.3% of those who lived (p = 0.0002) and funisitis was present in 4.1% of those who died versus 1.5% of those who lived, (p = 0.005). Across all three sites, in the placentas of the 201 term controls, 18.9% had any inflammation, 16.9% had chorioamnionitis, 5.5% had funisitis, 0.5% had intervillitis and none had villitis. Overall, for stillbirths, any inflammation was observed in 30.2%, chorioamnionitis in 26.9%, funisitis in 5.7%, intervillitis in 6.0% and villitis in 2.2%. For the neonatal deaths, any inflammation was present in 24.9%, chorioamnionitis in 23.3%, funisitis in 8.1%, intervillitis in 1.9% and villitis in 0.5%. Compared with the placentas of term controls, in neonatal deaths, only chorioamnionitis was significantly increased (23.3% versus 16.9%, p = 0.05). Among stillbirths, the rates of any inflammation, chorioamnionitis, intervillitis and villitis were similar across the birthweight groups. However, funisitis was more common in the placentas of stillborn fetuses weighing 2500 g or more (13.8%) compared with 1.0% for those weighing less than 1000 g and 4.8% for stillborn fetuses weighing 1000-2499 g. In the PCR studies, Ureaplasma spp. were by far the most common pathogens found and generally were more commonly found in association with inflammatory lesions. CONCLUSIONS: Chorioamnionitis was the most common type of placental inflammatory lesion regardless of whether the placentas evaluated were from term controls, stillbirths or neonatal deaths. For stillbirths, inflammation in each inflammation category was more common than in the term controls and significantly more so for any inflammation, chorioamnionitis, intervillitis and villitis. For neonatal deaths, compared with the placentas of term controls, all inflammation categories were more common, but only significantly so for chorioamnionitis. Ureaplasma spp. were the most common organisms found in the placentas and were significantly associated with inflammation.


Assuntos
Corioamnionite , Morte Perinatal , Nascimento Prematuro , Feminino , Gravidez , Recém-Nascido , Humanos , Placenta/patologia , Corioamnionite/epidemiologia , Natimorto/epidemiologia , Estudos Prospectivos , Ásia Meridional , Recém-Nascido Prematuro , Inflamação/patologia , Nascimento Prematuro/epidemiologia , Nascimento Prematuro/patologia
16.
BJOG ; 130 Suppl 3: 53-60, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37530593

RESUMO

OBJECTIVE: Group B streptococcus (GBS) has been associated with adverse pregnancy outcomes, but few prospective studies have assessed its prevalence in low- and middle-income country settings. We sought to evaluate the prevalence of GBS by polymerase chain reaction (PCR) in internal organ tissues and placentas of deceased neonates and stillbirths. DESIGN: This was a prospective, observational study. SETTING: The study was conducted in hospitals in India and Pakistan. POPULATION: Pregnant women with stillbirths or preterm births were recruited at delivery, as was a group of women with term, live births, to serve as a control group. METHODS: A rectovaginal culture was collected from the women in Pakistan to assess GBS carriage. Using PCR, we evaluated GBS in various tissues of stillbirths and deceased neonates and their placentas, as well as the placentas of live-born preterm and term control infants. MAIN OUTCOME MEASURES: GBS identified by PCR in various tissues and the placentas; rate of stillbirths and 28-day neonatal deaths. RESULTS: The most obvious finding from this series of analyses from India and Pakistan was that no matter the country, the condition of the subject, the tissue studied or the methodology used, the prevalence of GBS was low, generally ranging between 3% and 6%. Among the risk factors evaluated, only GBS positivity in primigravidae was increased. CONCLUSIONS: GBS diagnosed by PCR was identified in <6% of internal organs of stillbirths and neonatal deaths, and their placentas, and control groups in South Asian sites. This is consistent with other reports from South Asia and is lower than the reported GBS rates from the USA, Europe and Africa.


Assuntos
Morte Perinatal , Complicações Infecciosas na Gravidez , Infecções Estreptocócicas , Feminino , Humanos , Recém-Nascido , Gravidez , Ásia Meridional , Morte Perinatal/etiologia , Placenta , Complicações Infecciosas na Gravidez/epidemiologia , Complicações Infecciosas na Gravidez/diagnóstico , Prevalência , Estudos Prospectivos , Natimorto/epidemiologia , Infecções Estreptocócicas/epidemiologia , Infecções Estreptocócicas/diagnóstico , Streptococcus agalactiae/genética
17.
BJOG ; 130 Suppl 3: 26-35, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37592743

RESUMO

The PURPOSe study was a prospective, observational study conducted in India and Pakistan to determine the cause of death for stillbirths and preterm neonatal deaths, using clinical data together with minimally invasive tissue sampling (MITS) and the histologic and polymerase chain reaction (PCR) evaluation of fetal/neonatal tissues and the placenta. After evaluating all available data, an independent panel chose a maternal, a placental and a fetal/neonatal cause of death. Here, we summarise the major results. Among the most important findings were that most stillbirths were caused by fetal asphyxia, often preceded by placental malperfusion, and clinically associated with pre-eclampsia, placental abruption and a small-for-gestational-age fetus. The preterm neonatal deaths were primarily caused by birth asphyxia, followed by various infections. An important finding was that many of the preterm neonatal deaths were caused by a nosocomial infection acquired after neonatal intensive care (NICU) admission; the most common organisms were Acinetobacter baumannii, followed by Klebsiella pneumoniae, Escherichia coli/Shigella and Haemophilus influenzae. Group B streptococcus was less commonly present in the placentas or internal organs of the neonatal deaths.


Assuntos
Asfixia Neonatal , Morte Perinatal , Recém-Nascido , Feminino , Gravidez , Humanos , Natimorto/epidemiologia , Morte Perinatal/etiologia , Estudos Prospectivos , Paquistão/epidemiologia , Causas de Morte , Asfixia/complicações , Asfixia/patologia , Placenta/patologia , Índia/epidemiologia , Asfixia Neonatal/complicações , Estudos Observacionais como Assunto
18.
Asia Pac J Public Health ; 35(6-7): 433-436, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37635379

RESUMO

Binge eating (BE), defined as uncontrolled overconsumption of food, is associated with poorer health status. We aimed to characterize the factors associated with BE among Chinese college students. University students from two universities in Hong Kong (n = 267) completed an anonymous online questionnaire that contained background questions, the Binge Eating Disorder Screener-7, Depression, Anxiety, and Stress Scales-21 (DASS-21), and Adolescent Lifestyle Questionnaire (ALQ) between June and August 2022. Multiple logistic regression and two-sample independent t-test were conducted to test the association of study variables with BE. In this university sample, 36.8% of males and 21.4% of females were classified as engaging in BE in the last three months. BE was statistically significantly associated with higher body mass index (BMI), more depressive symptoms, and lower ALQ nutrition scores among males and lower BMI, more depressive, anxiety, and stress symptoms among females. BE was significantly associated with various factors in both male and female university students in Hong Kong; thereby, university health promotion programs should include the management of BE. BE should be a prominent focus of health promotion interventions in conjunction with mental health promotion in the region.


Assuntos
Transtorno da Compulsão Alimentar , Feminino , Humanos , Masculino , Povo Asiático/estatística & dados numéricos , Transtorno da Compulsão Alimentar/epidemiologia , Hong Kong/epidemiologia , Estudantes/estatística & dados numéricos , Universidades/estatística & dados numéricos
19.
Int Forum Allergy Rhinol ; 13(12): 2205-2230, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37300852

RESUMO

BACKGROUND: There is clear evidence that the prevalence of primary antibody deficiency (PAD) is higher in patients with recurrent and chronic rhinosinusitis (CRS) than in the general population. The purpose of this multi-institutional and multidisciplinary evidence-based review with recommendations (EBRR) is to thoroughly review the literature on rhinosinusitis with PAD, summarize the existing evidence, and provide recommendations on the evaluation and management of rhinosinusitis in patients with PAD. METHODS: The PubMed, EMBASE, and Cochrane databases were systematically reviewed from inception through August 2022. Studies on the evaluation and management of rhinosinusitis in PAD patients were included. An iterative review process was utilized in accordance with EBRR guidelines. Levels of evidence and recommendations on the evaluation and management principles for PAD were generated. RESULTS: A total of 42 studies were included in this evidence-based review. These studies were evaluated on incidence of PAD in rhinosinusitis patients, incidence of rhinosinusitis in PAD patients, and on the different treatment modalities used and their outcome. The aggregate quality of evidence was varied across reviewed domains. CONCLUSION: Based on the currently available evidence, PAD can occur in up to 50% of patients with recalcitrant CRS. Despite the presence of multiple studies addressing rhinosinusitis and PAD, the level of evidence supporting different treatment options continues to be lacking. Optimal management requires a multidisciplinary approach through collaboration with clinical immunology. There is need for higher-level studies that compare different treatments in patients with PAD and rhinosinusitis.


Assuntos
Doenças da Imunodeficiência Primária , Rinite , Sinusite , Humanos , Adulto , Rinite/diagnóstico , Rinite/epidemiologia , Rinite/terapia , Sinusite/diagnóstico , Sinusite/epidemiologia , Sinusite/terapia , Doença Crônica , Prevalência
20.
Psychol Serv ; 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37261764

RESUMO

It is essential for mental health services to be equitably accessible and utilized. The literature on mental health service utilization has, to date, been focused largely on in-person care. This quality assurance project evaluated telemental health (TMH) utilization rates among Veterans by race and ethnicity. Following the rapid expansion of TMH in response to the COVID-19 pandemic, we also explored whether TMH use across racial and ethnic Veteran groups changed after the onset of the pandemic. Using chi-square analyses, we compared the observed race and ethnicity of Veterans receiving TMH to the expected race and ethnicity of Veterans receiving TMH, controlling for rurality. We found that TMH was not being utilized by all racial and ethnic groups within the Veteran population as would be expected, both before and during the pandemic. Improvements were noted during the pandemic when much of outpatient mental health care was converted to telehealth. The strengths and limitations of this project, recommendations for TMH, and potential future directions are discussed. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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