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Journal of Korean Medical Science May 2024
PubMed: 38742295
DOI: 10.3346/jkms.2024.39.e170 -
Journal of Korean Medical Science May 2024
PubMed: 38711320
DOI: 10.3346/jkms.2024.39.e161 -
ENeuro May 2024The voltage-gated calcium channel subunit α2δ-2 controls calcium-dependent signaling in neurons, and loss of this subunit causes epilepsy in both mice and humans. To...
The voltage-gated calcium channel subunit α2δ-2 controls calcium-dependent signaling in neurons, and loss of this subunit causes epilepsy in both mice and humans. To determine whether mice without α2δ-2 demonstrate hippocampal activation or histopathological changes associated with seizure activity, we measured expression of the activity-dependent gene c and various histopathological correlates of temporal lobe epilepsy (TLE) in hippocampal tissue from wild-type (WT) and α2δ-2 knock-out ( KO) mice using immunohistochemical staining and confocal microscopy. Both genotypes demonstrated similarly sparse c- and expressions within the hippocampal dentate granule cell layer (GCL) at baseline, consistent with no difference in basal activity of granule cells between genotypes. Surprisingly, when mice were assayed 1 h after handling-associated convulsions, KO mice had fewer c--positive cells but dramatically increased expression in the dentate gyrus compared with WT mice. After administration of a subthreshold pentylenetetrazol dose, however, KO mice dentate had significantly more c- expression compared with WT mice. Other histopathological markers of TLE in these mice, including markers of neurogenesis, glial activation, and mossy fiber sprouting, were similar between WT and KO mice, apart from a small but statistically significant increase in hilar mossy cell density, opposite to what is typically found in mice with TLE. This suggests that the differences in seizure-associated dentate gyrus function in the absence of α2δ-2 protein are likely due to altered functional properties of the network without associated structural changes in the hippocampus at the typical age of seizure onset.
Topics: Animals; Mice, Knockout; Seizures; Hippocampus; Proto-Oncogene Proteins c-fos; Male; Calcium Channels; Mice, Inbred C57BL; Pentylenetetrazole; Mice; Disease Models, Animal; Neurons; Convulsants
PubMed: 38749701
DOI: 10.1523/ENEURO.0486-23.2024 -
BMJ Open May 2024To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).
Association between secondhand smoke exposure and serum sex hormone concentrations among US female adults: a cross-sectional analysis using data from the National Health and Nutrition Examination Survey, 2013-2016.
OBJECTIVE
To estimate the association between secondhand smoke (SHS) exposure and serum sex hormone concentrations in female adults (never smokers and former smokers).
DESIGN
Cross-sectional analysis.
SETTING
US National Health and Nutrition Examination Survey, 2013-2016.
OUTCOME MEASURES
Serum sex hormone measures included total testosterone (TT) and oestradiol (E2), sex hormone-binding globulin (SHBG), the ratio of TT and E2 and free androgen index (FAI). Isotope dilution-liquid chromatography tandem mass spectrometry was used to measure serum TT and E2. SHBG was measured using immunoassay. The ratio of TT and E2 and FAI were calculated. SHS exposure was defined as serum cotinine concentration of 0.05-10 ng/mL.
PARTICIPANTS
A total of 622 female participants aged ≥20 years were included in the analysis.
RESULTS
For never smokers, a doubling of serum cotinine concentration was associated with a 2.85% (95% CI 0.29% to 5.47%) increase in TT concentration and a 6.29% (95% CI 0.68% to 12.23%) increase in E2 in fully adjusted models. The never smokers in the highest quartile (Q4) of serum cotinine level exhibited a 10.30% (95% CI 0.78% to 20.72%) increase in TT concentration and a 27.75% (95% CI 5.17% to 55.17%) increase in E2 compared with those in the lowest quartile (Q1). For former smokers, SHBG was reduced by 4.36% (95% CI -8.47% to -0.07%, p for trend=0.049) when the serum cotinine level was doubled, and the SHBG of those in Q4 was reduced by 17.58% (95% CI -31.33% to -1.07%, p for trend=0.018) compared with those in Q1.
CONCLUSION
SHS was associated with serum sex hormone concentrations among female adults. In never smokers, SHS was associated with increased levels of TT and E2. In former smokers, SHS was associated with decreased SHBG levels.
Topics: Humans; Female; Tobacco Smoke Pollution; Cross-Sectional Studies; Nutrition Surveys; Adult; Cotinine; United States; Middle Aged; Sex Hormone-Binding Globulin; Estradiol; Testosterone; Young Adult; Gonadal Steroid Hormones; Tandem Mass Spectrometry
PubMed: 38749695
DOI: 10.1136/bmjopen-2023-073527 -
BMJ Open May 2024Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of...
INTRODUCTION
Chronic rhinosinusitis with nasal polyps (CRSwNP) is a frequent condition affecting approximately 2% of the population. Medical treatment consists long-term use of intranasal corticosteroids and short-term use of oral corticosteroids, in adjunct with saline solution rinses. Surgical management is proposed in patients who failed after medical treatment. In France, two biologics are reimbursed in case of severe uncontrolled CRSwNP despite medical treatment and endoscopic sinus surgery. Waiting for head-to-head biologics comparison, studies should report the efficacy and safety of biologics in large real-life cohorts. This study protocol describes the aims and methods of a prospective, observational, national, multicentric cohort of patients with CRSwNP treated with biologics.
METHODS AND ANALYSIS
The BIOlogics in severe nasal POlyposis SurvEy is a French multicentre prospective observational cohort study. The main aim is to assess the efficacy and tolerance of biologics in patients with CRSwNP, with or without association with other type 2 diseases, and to determine the strategies in case of uncontrolled disease under biologics. Patients over 18 years old requiring biologics for CRSwNP in accordance with its marketing approval in France (ie, severe nasal polyposis, with lack of control under nasal corticosteroid, systemic corticosteroids and surgery) are invited to participate. Collected data include topical history of surgical procedures and biologics, medication and use of systemic corticosteroids, visual analogical scales for specific symptoms, Sino-Nasal Outcome Test-22 questionnaire, nasal polyp score, asthma control test, Lund-Mackay score on CT scan and IgE concentration and eosinophilic count on blood sample.
TRIAL REGISTRATION
NCT05228041/DRI_2021/0030.
Topics: Humans; Nasal Polyps; Sinusitis; Chronic Disease; Rhinitis; Prospective Studies; Biological Products; France; Observational Studies as Topic; Omalizumab; Multicenter Studies as Topic; Rhinosinusitis
PubMed: 38749694
DOI: 10.1136/bmjopen-2023-083112 -
BMJ Open May 2024To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.
OBJECTIVES
To estimate the shape of the causal relationship between body mass index (BMI) and mortality risk in a Mendelian randomisation framework.
DESIGN
Mendelian randomisation analyses of two prospective population-based cohorts.
SETTING
Individuals of European ancestries living in Norway or the UK.
PARTICIPANTS
56 150 participants from the Trøndelag Health Study (HUNT) in Norway and 366 385 participants from UK Biobank recruited by postal invitation.
OUTCOMES
All-cause mortality and cause-specific mortality (cardiovascular, cancer, non-cardiovascular non-cancer).
RESULTS
A previously published non-linear Mendelian randomisation analysis of these data using the residual stratification method suggested a J-shaped association between genetically predicted BMI and mortality outcomes with the lowest mortality risk at a BMI of around 25 kg/m. However, the 'constant genetic effect' assumption required by this method is violated. The reanalysis of these data using the more reliable doubly-ranked stratification method provided some indication of a J-shaped relationship, but with much less certainty as there was less precision in estimates at the lower end of the BMI distribution. Evidence for a harmful effect of reducing BMI at low BMI levels was only present in some analyses, and where present, only below 20 kg/m. A harmful effect of increasing BMI for all-cause mortality was evident above 25 kg/m, for cardiovascular mortality above 24 kg/m, for cancer mortality above 30 kg/m and for non-cardiovascular non-cancer mortality above 26 kg/m. In UK Biobank, the association between genetically predicted BMI and mortality at high BMI levels was stronger in women than in men.
CONCLUSION
This research challenges findings from previous conventional observational epidemiology and Mendelian randomisation investigations that the lowest level of mortality risk is at a BMI level of around 25 kg/m. Our results provide some evidence that reductions in BMI will increase mortality risk for a small proportion of the population, and clear evidence that increases in BMI will increase mortality risk for those with BMI above 25 kg/m.
Topics: Humans; Mendelian Randomization Analysis; Body Mass Index; United Kingdom; Female; Male; Middle Aged; Aged; Prospective Studies; Norway; Biological Specimen Banks; Neoplasms; Cardiovascular Diseases; Adult; Cause of Death; Mortality; Risk Factors; UK Biobank
PubMed: 38749693
DOI: 10.1136/bmjopen-2023-081399 -
BMJ Open May 2024Childhood asthma is a highly prevalent chronic disease. A failure to implement patient education programmes may result in increased morbidity, despite the availability...
Study protocol of a prospective, interventional non-randomised trial investigating the impact of asthma education on specific disease understanding, health literacy and therapy outcome in childhood.
INTRODUCTION
Childhood asthma is a highly prevalent chronic disease. A failure to implement patient education programmes may result in increased morbidity, despite the availability of distinct diagnostic and therapeutic approaches. Patients with lower socioeconomic status (SES) tend to have a higher asthma prevalence. Moreover, the progression of asthma is significantly influenced by factors such as health literacy and the children's specific knowledge about the condition. With this trial, the primary objective is to evaluate whether asthma education enhances specific disease understanding in children with asthma (primary outcome). Secondary objectives include evaluating training effects on health literacy, retention rates of information, 'Children Asthma Control Test' (C-ACT) score, frequency of emergency room and physician visits (secondary outcomes) and whether SES influences training effects.
METHODS AND ANALYSIS
To address the research objectives, this study comprises two projects. The first subproject will investigate the influence of asthma training on the development of disease understanding and health literacy. The second subproject will analyse the influence of SES on the outcome of children participating in asthma training. This research is designed as a comparative, non-randomised study involving two paediatric groups between the ages of ≥7 and < 14 years. After being diagnosed with asthma, the intervention group undergoes standardised psychoeducational asthma training at a certified centre associated with paediatricians in private practice in Germany, following the recommendations of the 'Arbeitsgruppe Asthmaschulung im Kindes- und Jugendalter e.V.', a national association aiming to establish uniform and guideline-based standards for patient education in children and adolescents. The comparison group receives a significantly shorter period of education and instruction on the usage of asthma medication at outpatient clinics. Data will be collected from patients and their parents at three specific survey time points, based on standardised tools.To describe mean differences between the intervention and control group over time (subproject 1), a repeated-measures analysis of variance (ANOVA) will be conducted. In subproject 2, multivariate linear regression analysis will be used to analyse the variables determining the changes in specific disease understanding and health literacy, including SES. The sample size calculation is based on a mixed ANOVA model with two groups and two measurements resulting in a total of 126 participants.
ETHICS AND DISSEMINATION
All protocols and a positive ethics approval were obtained from the Witten/Herdecke University, Germany (S-159, 2023; application submission: 24 June 2023, final vote: 10 July 2023). Furthermore, the study was registered at the German Clinical Trials Register (DRKS), DRKS00032423. The application submission was on 3 August 2023, and the final approval was on 4 August 2023. The results will be disseminated among experts and participants and will be published in peer-reviewed, international journal with open access.
TRIAL REGISTRATION NUMBER
DRKS00032423.
Topics: Humans; Asthma; Health Literacy; Child; Patient Education as Topic; Prospective Studies; Adolescent; Male; Female; Health Knowledge, Attitudes, Practice; Non-Randomized Controlled Trials as Topic; Germany
PubMed: 38749686
DOI: 10.1136/bmjopen-2023-083180 -
BMJ Open May 2024To estimate Chinese rural residents' willingness degree of initially contacting primary healthcare (PHC) under uncertainty in healthcare and to explore its influencing...
OBJECTIVE
To estimate Chinese rural residents' willingness degree of initially contacting primary healthcare (PHC) under uncertainty in healthcare and to explore its influencing factors.
SETTING
This study collected primary data from rural residents in Dangyang, Hubei Province in China.
PARTICIPANTS
The study investigated 782 residents and 701 finished the survey. The response rate was 89.64%. A further 27 residents failed the internal consistency test, so the effective sample size was 674.
DESIGN
In this cross-sectional study, residents' willingness was reflected by the threshold of disease severity for PHC (TDSP), the individual maximal disease scope for considering PHC based on residents' decision-making framework. TDSP was measured through scenario tests. Univariate analysis and unordered multiple logistic regression were used to explore the influencing factors of three-level TDSP: low, general, and high.
RESULTS
Only 28.2% of respondents had high TDSP and high willingness towards PHC. Compared with general TDSP, respondents who were younger than 40 (OR 7.344, 95% CI 2.463 to 21.894), rich (OR 1.913, 95% CI 1.083 to 3.379), highly risk-averse (OR 1.958, 95% CI 1.016 to 3.774), had substitute medical decision-maker (OR value of parent/child was 2.738, 95% CI 1.386 to 5.411) and had no visits to PHC in the last 6 months (OR 2.098, 95% CI 1.316 to 3.346) tended to have low TDSP and low willingness towards PHC. Compared with general TDSP, no factors were found to significantly influence respondents' high TDSP.
CONCLUSIONS
TDSP can be a good indicator of residents' willingness. TDSP results demonstrate rural residents' generally low willingness towards first-contact with PHC that some residents refuse to consider PHC even for mild diseases. This study provides practical significance for elaborating the underutilisation of PHC from resident decision-making and offers advice to policymakers and researchers for future modifications.
Topics: Humans; Cross-Sectional Studies; China; Primary Health Care; Male; Female; Adult; Rural Population; Middle Aged; Uncertainty; Patient Acceptance of Health Care; Logistic Models; Surveys and Questionnaires; Decision Making; Young Adult; Aged
PubMed: 38749685
DOI: 10.1136/bmjopen-2023-077618 -
BMJ Open May 2024To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best...
OBJECTIVE
To evaluate the effectiveness of standardised antiretroviral therapy (ART) among different HIV subtypes in people living with HIV/AIDS (PLWHA), and to screen the best ART regimen for this patient population.
DESIGN
A retrospective cohort study was performed, and PLWHA residing in Huzhou, China, between 2018 and 2020, were enrolled.
SETTING AND PARTICIPANTS
Data from 625 patients, who were newly diagnosed with HIV/AIDS in the AIDS Prevention and Control Information System in Huzhou between 2018 and 2020, were reviewed.
ANALYSIS AND OUTCOME MEASURES
Data regarding demographic characteristics and laboratory investigation results were collected. Immune system recovery was used to assess the effectiveness of ART, and an increased percentage of CD4 T lymphocyte counts >30% after receiving ART for >1 year was determined as immunopositive. A multiple logistic regression model was used to comprehensively quantify the association between PLWHA immunological response status and virus subtype. In addition, the joint association between different subtypes and treatment regimens on immunological response status was investigated.
RESULTS
Among 326 enrolled PLWHA with circulating recombinant forms (CRFs) CRF01_AE, CRF07_BC and other HIV/AIDS subtypes, the percentages of immunopositivity were 74.0%, 65.6% and 69.6%, respectively. According to multivariate logistic regression models, there was no difference in the immunological response between patients with CRF01_AE, CRF07_BC and other subtypes of HIV/AIDS who underwent ART (CRF07_BC: adjusted OR (aOR) (95% CI) = 0.8 (0.4 to 1.4); other subtypes: aOR (95% CI) = 1.2 (0.6 to 2.3)). There was no evidence of an obvious joint association between HIV subtypes and ART regimens on immunological response.
CONCLUSIONS
Standardised ART was beneficial to all PLWHA, regardless of HIV subtypes, although it was more effective, to some extent, in PLWHA with CRF01_AE.
Topics: Humans; Retrospective Studies; Male; Female; Adult; Middle Aged; HIV Infections; CD4 Lymphocyte Count; China; Anti-HIV Agents; Acquired Immunodeficiency Syndrome; HIV-1; Treatment Outcome
PubMed: 38749684
DOI: 10.1136/bmjopen-2023-072597 -
BMJ Open May 2024Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients... (Observational Study)
Observational Study
Protocol for the Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study: a prospective, observational, multicentre cohort study of acute spinal cord injury.
INTRODUCTION
Spinal cord injury (SCI) is a catastrophic event with devastating physical, social and occupational consequences for patients and their families. The number of patients with acute SCI in China continues to grow rapidly, but there have been no large prospective cohort studies of patients with acute SCI. This proposed study aims to establish a multicentre, extensive sample cohort of clinical data and biological samples of patients in China, which would aid the systematisation and standardisation of clinical research and treatment of acute SCI, thus reducing the heavy burden of acute SCI on patients and society.
METHODS AND ANALYSIS
The Chinese Real-World Evidence for Acute Spinal Cord Injury (ChiRES) study is an observational, multicentre cohort study of patients with acute SCI admitted to the Qilu Hospital of Shandong University and other participating centres with prospective collection of their clinical data and biological samples. We aim to recruit 2097 patients in this study. Demographics, disease history, emergency intervention information, motor and sensory examinations, surgical information, medication information and rehabilitation evaluation will be recorded. This will facilitate the development of a prediction model for complications and prognosis of patients with acute SCI and an evaluation of the current management of acute SCI. Among these variables, detailed information on surgical treatment will also be used to assess procedures for acute SCI treatment. Outcome measurements, including the International Standard for Neurological Classification of Spinal Cord Injury examinations, the occurrence of complications and death, will be performed repeatedly during follow-up. We will analyse imaging data and blood samples to develop SCI imaging markers and biomarkers.
ETHICS AND DISSEMINATION
This study protocol has been approved by the Medical Ethics Committee of the Qilu Hospital of Shandong University and all other participating centres. The findings will be disseminated in peer-reviewed journals and academic conferences.
Topics: Humans; Spinal Cord Injuries; Prospective Studies; China; Observational Studies as Topic; Research Design; Multicenter Studies as Topic; Female; Adult; Male; East Asian People
PubMed: 38749680
DOI: 10.1136/bmjopen-2023-080358