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The study evaluated the prevalence of gonorrhoea and chlamydia infections and find out other non-infectious diseases in sexually active young males with urethritis-like symptoms and their treatment outcomes. We retrospectively reviewed the young adult males (aged 20-50 years) who visited our clinic with urethritis symptoms from March 2019 to April 2022. All patients underwent urinalysis, urine culture, and urinary polymerase chain reaction (PCR) testing for gonorrhoea and chlamydia. Student's t-test and Pearson's chi-square test were used to compare the differences between the triple-negative group (i.e., negative results in urinalysis, urine culture, and urinary PCR) and the any-positive group. Logistic regression analyses were used to evaluate the predictive factors for positive PCR results for gonorrhoea or chlamydia in patients with negative urinalysis and urine culture. Of the 365 participants with urethritis-like symptoms, 139 patients were diagnosed of gonococcal or chlamydia urethritis. Among the 202 patients with negative urinalysis and urine culture, 60 patients were diagnosed with gonorrhoea or chlamydia using PCR. Urethral discharge was an independent predictor. 142 patients with triple negative results were attributed to other non-infectious diseases. Empirical antibiotic treatment is recommended for patients with urethritis symptoms showing positive or negative urinalysis results but with urethral discharge.
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Infecciones por Chlamydia , Gonorrea , Enfermedades no Transmisibles , Uretritis , Masculino , Adulto Joven , Humanos , Uretritis/diagnóstico , Uretritis/tratamiento farmacológico , Uretritis/epidemiología , Gonorrea/diagnóstico , Gonorrea/tratamiento farmacológico , Gonorrea/epidemiología , Estudios Retrospectivos , Chlamydia trachomatis , Infecciones por Chlamydia/diagnóstico , Infecciones por Chlamydia/tratamiento farmacológico , Infecciones por Chlamydia/epidemiología , Resultado del TratamientoRESUMEN
Chronic obstructive pulmonary disease (COPD) contributes significantly to the death of people worldwide, especially the elderly. An essential feature of COPD is pulmonary inflammation, which results from long-term exposure to noxious substances from cigarette smoking and other environmental pollutants. Pulmonary inflammatory mediators spill over to the blood, leading to systemic inflammation, which is believed to play a significant role in the onset of a host of comorbidities associated with COPD. A substantial comorbidity of concern in COPD patients that is often overlooked in COPD management is cognitive impairment. The exact pathophysiology of cognitive impairment in COPD patients remains a mystery; however, hypoxia, oxidative stress, systemic inflammation, and cerebral manifestations of these conditions are believed to play crucial roles. Furthermore, the use of medications to treat cognitive impairment symptomatology in COPD patients has been reported to be associated with life-threatening adverse effects, hence the need for alternative medications with reduced side effects. In this Review, we aim to discuss the impact of cognitive impairment in COPD management and the potential mechanisms associated with increased risk of cognitive impairment in COPD patients. The promising roles of omega-3 polyunsaturated fatty acids (ω-3 PUFAs) in improving cognitive deficits in COPD patients are also discussed. Interestingly, ω-3 PUFAs can potentially enhance the cognitive impairment symptomatology associated with COPD because they can modulate inflammatory processes, activate the antioxidant defence system, and promote amyloid-beta clearance from the brain. Thus, clinical studies are crucial to assess the efficacy of ω-3 PUFAs in managing cognitive impairment in COPD patients.
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Trastornos del Conocimiento , Disfunción Cognitiva , Ácidos Grasos Omega-3 , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Anciano , Ácidos Grasos Omega-3/uso terapéutico , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/tratamiento farmacológico , Disfunción Cognitiva/tratamiento farmacológico , Inflamación/tratamiento farmacológico , Trastornos del Conocimiento/tratamiento farmacológicoRESUMEN
OBJECTIVE: To evaluate the impacts of messenger RNA coronavirus disease 2019 (COVID-19) vaccines in Taiwanese pregnant women in terms of obstetrical and neonatal outcomes. METHODS: The authors prospectively followed up 450 pregnant women receiving vaccination at a single center. Patients recorded prespecified adverse reactions via a mobile application up to 30 days after the first and second doses. Obstetrical and neonatal outcomes were compared with those of pregnant women, during the same period, who did not undergo vaccination. RESULTS: Among the 387 women who received the first dose and were followed up for 30 days, injection site pain, fatigue, injection site swelling, muscle ache, and headache were the most prevalent side effects. There were 4.7-, 5.7-, 7.1-, and 9.3-fold increases in fatigue, injection site swelling, muscle ache, and headache, respectively, among the 231 women who received the second dose. Most of the side effects resolved by 14 days and all resolved by 30 days after each doses. There were no significant differences (P > 0.05) in obstetrical and neonatal morbidity or mortality between the vaccinated and unvaccinated cohorts. CONCLUSION: No serious adverse reactions were noted among pregnant women receiving messenger RNA vaccinations with comparable obstetrical and neonatal outcomes to unvaccinated pregnant women.
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COVID-19 , Embarazo , Recién Nacido , Humanos , Femenino , COVID-19/prevención & control , Estudios de Casos y Controles , Vacunas contra la COVID-19/efectos adversos , Mujeres Embarazadas , Estudios Prospectivos , Fatiga , Cefalea/inducido químicamente , Cefalea/epidemiología , Mialgia , ARN Mensajero , VacunaciónRESUMEN
Background: There are many different variants of squamous cell carcinoma (SCC), and verrucous carcinoma (VC) is a rare and highly differentiated SCC. Due to its preference of local invasion, regional lymphatic involvement rarely occurs. VC is difficult to diagnose using conventional pap smear or cervical punch biopsy, in which adequate stroma including bulbous rete pegs is required for a definitive diagnosis. Surgical management is recommended as the first-line treatment with radiotherapy forbidden due to the risk of anaplastic transformation. Case report: We presented a 59-year-old Taiwanese female who had postmenopausal bleeding for three months with two consecutive normal pap smear and biopsy at other hospital. Pelvic examination showed a necrotic fungating cervical mass with upper 1/3 vaginal involvement. Colposcopic guided cervical biopsy and fractional dilatation and curettage revealed verrucous hyperplasia (VH) with negative high-risk HPV typing. Pelvic 3T magnetic resonance imaging (MRI) was arranged, and a 3.7 × 3.6 × 4.0 cm necrotic mass at the cervix with an enlarged left pelvic lymph node was found. Positron emission tomography with computed tomography (PET/CT) demonstrated avid uptake at the cervix and left pelvic lymph node. Surgical intervention was performed due to highly suspicious of cervical verrucous carcinoma with positive pelvic lymph node. The final pathologic report was a well-differentiated verrucous carcinoma, IIA2 by International Federation of Gynecology and Obstetrics (FIGO) classification. Conclusion: VC is difficult to diagnose preoperatively, and surgical excision is recommended as the first-line treatment.
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BACKGROUND: Use of interprofessional education has greatly expanded and is widely used to foster interprofessional collaborative practice competency in health professionals, especially during medical emergencies. Identifying the interprofessional education delivery mode that can maximize learning outcomes within available resources is crucial for achieving the sustainability of an interprofessional education program. OBJECTIVES: To examine the learning outcomes of simulation-based interprofessional education and video-enhanced interactive discussion interprofessional education modules and to analyze the variable costs between these two interprofessional education modules. DESIGN: A prospective quasi-experimental study. SETTING: A medical university in Northern Taiwan. PARTICIPANTS: 24 medical students and 48 nursing students enrolled in a 4-week simulation-based interprofessional education or video-enhanced interactive discussion interprofessional education program. METHODS: Students' medical task performance, critical medical task performance, team behavior performance, and interprofessional collaboration attitude were examined at the pretest and posttest by using an objective structured checklist and team performance rating scale with a hands-on simulation model and structured questionnaires. The variable costs for simulation-based interprofessional education and video-enhanced interactive discussion interprofessional education were estimated upon the completion of the course. RESULTS: All learning outcomes significantly improved for both the groups from the pretest to posttest. After the intervention, the simulation-based interprofessional education group exhibited significantly higher scores in medical task performance, critical medical task performance and team behavior performance than the video-enhanced interactive discussion interprofessional education group at the posttest. No significant difference was noted in interprofessional collaboration attitude between the groups. Cost analysis revealed that the simulation-based interprofessional education program was approximately two times more expensive in terms of staffing costs and required 1.3 times greater space charges than the video-enhanced interactive discussion interprofessional education program. CONCLUSION: Both simulation-based interprofessional education and video-enhanced interactive discussion interprofessional education modules effectively improved medical and nursing students' medical task performance, critical medical task performance and team behavior performance. The simulation-based interprofessional education group had more favorable learning outcomes, but the associated costs were higher. Educators should consider both learning outcomes and cost when choosing a design strategy simulation-based interprofessional education vs. video-enhanced interactive discussion interprofessional education for interprofessional education module development.
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Estudiantes de Medicina , Estudiantes de Enfermería , Actitud del Personal de Salud , Humanos , Educación Interprofesional , Relaciones Interprofesionales , Estudios ProspectivosRESUMEN
ABSTRACT: Cerebrovascular disease is the second commonest cause of mortality globally and among the commonest causes of disability. However, research executed to probe the heavy metal exposure-stroke incidence relationship is scarce. Accordingly, we executed our study to probe the relationship of heavy metal concentrations (ie, concentrations of lead [Pb], mercury [Hg], cadmium [Cd], and arsenic) in the serum and urine of acute ischemic stroke (AIS) patients with several patient variables.For enrollment, we chose patients who had a first AIS within 7âdays after the onset of a stroke. Thus, 33 newly diagnosed patients with AIS were recruited. We determined the aforementioned metals' concentrations by executing inductively coupled plasma mass spectrometry. We also gauged the association between such metal concentrations and patient variables by employing Spearman correlation coefficient. To examine the differences in metal concentrations between the different variables, we implemented an independent Mann-Whitney U test.In our cohort analysis, we noted serum Pb and Cd concentrations to be positively correlated with serum creatinine and hemoglobin. Serum and urine Cd concentrations had a negative correlation with impaired HbA1c in AIS patients. Urine Hg had a positive correlation with C-reactive protein in the participants. Participants who smoked or consumed alcohol had significantly higher Pb and Cd levels in serum than did those who neither smoked nor drank. Patients with AIS who smoked or consumed alcohol had high levels of serum Pb and serum Cd than did those who did not. Patients with AIS who consumed alcohol had significantly higher Pb and Hg urine concentrations than did those who did not.Our study indicated that serum Cd and Pb elevation increased the AIS risk in southern Taiwan patients.
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Exposición a Riesgos Ambientales , Accidente Cerebrovascular Isquémico/epidemiología , Metales Pesados/sangre , Metales Pesados/orina , Adulto , Anciano , Arsénico/efectos adversos , Arsénico/sangre , Arsénico/orina , Cadmio/efectos adversos , Cadmio/sangre , Cadmio/orina , Estudios Transversales , Femenino , Humanos , Accidente Cerebrovascular Isquémico/sangre , Plomo/efectos adversos , Plomo/sangre , Plomo/orina , Masculino , Mercurio/sangre , Mercurio/orina , Metales Pesados/efectos adversos , Persona de Mediana Edad , Fumar , Taiwán/epidemiologíaRESUMEN
Topological superconductors have attracted tremendous excitement as they are predicted to host Majorana zero modes that can be utilized for topological quantum computing. Candidate topological superconductor Sn1-xInxTe thin films (0 < x < 0.3) grown by molecular beam epitaxy and strained in the (111) plane are shown to host quantum interference effects in the conductivity coexisting with superconducting fluctuations above the critical temperature Tc. An analysis of the normal state magnetoresistance reveals these effects. A crossover from weak antilocalization to localization is consistently observed in superconducting samples, indicating that superconductivity originates dominantly from charge carriers occupying trivial states that may be strongly spin-orbit split. A large enhancement of the conductivity is observed above Tc, indicating the presence of superconducting fluctuations. Our results motivate a re-examination of the debated pairing symmetry of this material when subjected to quantum confinement and lattice strain.
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BACKGROUND: In Alzheimer's disease (AD), cognitive impairment begins 10-15 years later than neurodegeneration in the brain. Plasma biomarkers are promising candidates for assessing neurodegeneration in people with normal cognition. It has been reported that subjects with the concentration of plasma amyloid-ß 1-42×total tau protein higher than 455âpg2/ml2 are assessed as having a high risk of amnesic mild impairment or AD, denoted as high risk of AD (HRAD). OBJECTIVE: The prevalence of high-risk for dementia in cognitively normal controls is explored by assaying plasma biomarkers. METHODS: 422 subjects with normal cognition were enrolled around Taiwan. Plasma Aß1-40, Aß1-42, and T-Tau levels were assayed using immunomagnetic reduction to assess the risk of dementia. RESULTS: The results showed that 4.6% of young adults (age: 20-44 years), 8.5% of middle-aged adults (age: 45-64 years), and 7.3% of elderly adults (age: 65-90 years) had HRAD. The percentage of individuals with HRAD dramatically increased in middle-aged and elderly adults compared to young adults. CONCLUSION: The percentage of HRAD in cognitively normal subjects are approximately 10%, which reveals that the potentially public-health problem of AD in normal population. Although the subject having abnormal levels of Aß or tau is not definitely going on to develop cognitive declines or AD, the risk of suffering cognitive impairment in future is relatively high. Suitable managements are suggested for these high-risk cognitively normal population. Worth noting, attention should be paid to preventing cognitive impairment due to AD, not only in elderly adults but also middle-aged adults.
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The present study investigated the association between severity of depressive mood and nocturia in young Asian adult men. Participants were 3127 adult male Facebook users aged 20-40 years who could read and write traditional Chinese. Participants completed online questionnaires on demographic characteristics, frequency of waking to urinate during the night (International Prostate Symptoms Score [IPSS]), and frequency of depressive symptoms (Taiwanese Depression Questionnaire [TDQ]). Those who awoke to pass urine during the main sleep period were considered to have nocturia. Student's t test and Pearson's chi square test were used to compare participants with and without nocturia. Univariate and multivariate logistic regression were used to evaluate predictive factors for nocturia. One thousand four hundred thirty (45.7%) participants had nocturia, and 21.9% were suspected to have depression. Age over 30 years, body mass index over 25 kg/m2, and higher IPSS score (except times of nocturnal voiding) were factors predictive of nocturia. Higher TDQ somatic subscores, rather than affective/cognitive subscores, were also predictive of nocturia. Associations were found between normal-high TDQ scores and nocturia. Young men with nocturia at risk of developing depression should be identified with a culturally relevant questionnaire. Early referral for psychiatric assessment and intervention may be warranted.
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Nocturia/diagnóstico , Sueño/fisiología , Adulto , Humanos , Masculino , Nocturia/etiología , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
To ascertain the direct effects of water stress upon wheat plants (Triticum aestivum L.) and how these effects, in turn, influence the population growth of the bird cherry-oat aphid (Rhopalosiphum padi L.), we conducted a physiological analysis of wheat seedlings grown under three different watering regimes and subsequently determined the population parameters of the aphid using the age-stage, two-sex life table. A significantly higher content of free amino acids and soluble sugars were observed in wheat seedlings exposed to drought stress compared to seedlings that were well-watered and those that were grown under waterlogged conditions. Extended phloem salivation and stylet penetration with shorter duration of sustained ingestion from phloem was observed in an electrical penetration graph (EPG) of R. padi on drought-stressed wheat seedlings. This suggested that the aphid's feeding activity, as well as nutrient intake, were impeded. The significantly higher percentage of essential amino acids found in wheat seedlings grown under waterlogged conditions promoted significantly higher fecundity and intrinsic rate of increase in R. padi populations compared to aphids fed on drought-treated or well-watered wheat seedlings. Our findings suggest that wheat seedling responses to water stress involve changes in sap composition that are responsible for altering the aphids' nutrient intake and consequently affect their population growth. From a grower's perspective, extending wheat cultivation in a rice-wheat rotation paddy field during the winter season may not be economically profitable if the fields are chronically waterlogged, since this may potentially lead to a higher infestation of cereal aphids.
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Áfidos , Animales , Deshidratación , Nutrientes , Poaceae , Crecimiento Demográfico , TriticumRESUMEN
OBJECTIVES: Recent neuropathological research suggests that recognition memory supported by familiarity rather than recollection may be the earliest cognitive change in course of Alzheimer's disease (AD). Nonetheless, the findings on the issue of familiarity capacity in the prodromal AD remain inconsistent. Boundary extension (BE), in which the view recollected by the subject covers a wider angle than was actually observed, is a form of false memory. Given that BE occurs implicitly and automatically, it may be a candidate for assessing familiarity functioning in cases of AD. This was the issue explored in the current study. METHODS: One-hundred and six participants comprising a younger adult group (YA, n = 40), a healthy older adult group (OA, n = 40), and a group of patients with mild cognitive impairment (MCI, n = 26) underwent testing for BE and neuropsychological functions. Parts of OA and MCI underwent analysis for plasma tau levels. Receiver-operating characteristic analysis was used to assess memory associated with familiarity and recollection among participants. RESULTS: The OA and MCI groups could be differentiated by the degree of familiarity associated with BE, wherein the latter group displayed minimal familiarity. Among OAs, familiarity was positively associated with education level. We observed a correlation between plasma tau levels and various neuropsychological functions. Most of the associations between plasma tau levels and neuropsychological functions were mediated by education level. CONCLUSIONS: Our findings indicate that BE could detect early decline in familiarity and assess preserved cognitive functions in aging.
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Enfermedad de Alzheimer , Disfunción Cognitiva , Anciano , Enfermedad de Alzheimer/diagnóstico , Cognición , Disfunción Cognitiva/diagnóstico , Humanos , Recuerdo Mental , Pruebas Neuropsicológicas , Reconocimiento en PsicologíaRESUMEN
Monolayer WTe_{2}, a centrosymmetric transition metal dichacogenide, has recently been established as a quantum spin Hall insulator and found superconducting upon gating. Here we study the pairing symmetry and topological nature of superconducting WTe_{2} with a microscopic model at mean-field level. Surprisingly, we find that the spin-triplet phases in our phase diagram all host Majorana modes localized on two opposite corners. Even when the conventional pairing is favored, we find that an intermediate in-plane magnetic field exceeding the Pauli limit stabilizes an unconventional equal-spin pairing aligning with the field, which also hosts Majorana corner modes. Motivated by our findings, we obtain a recipe for two-dimensional superconductors featuring "higher-order topology" from the boundary perspective. Generally, a superconducting inversion-symmetric quantum spin Hall material whose normal-state Fermi surface is away from high-symmetry points, such as gated monolayer WTe_{2}, hosts Majorana corner modes if the superconductivity is parity-odd. We further point out that this higher-order phase is an inversion-protected topological crystalline superconductor and study the bulk-boundary correspondence. Finally, we discuss possible experiments for probing the Majorana corner modes. Our findings suggest superconducting monolayer WTe_{2} is a playground for higher-order topological superconductivity and possibly the first material realization for inversion-protected Majorana corner modes without utilizing proximity effect.
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Genome-editing techniques such as CRISPR/Cas9 have been widely used in crop functional genomics and improvement. To efficiently deliver the guide RNA and Cas9, most studies still rely on Agrobacterium-mediated transformation, which involves a selection marker gene. However, several limiting factors may impede the efficiency of screening transgene-free genome-edited plants, including the time needed to produce each life cycle, the response to selection reagents, and the labor costs of PCR-based genotyping. To overcome these disadvantages, we developed a simple and high-throughput method based on visual detection of antibiotics-derived H2O2 to verify transgene-free genome-edited plants. In transgenic rice containing hygromycin phosphotransferase (HPT), H2O2 content did not change in the presence of hygromycin B (HyB). In contrast, in transgenic-free rice plants with 10-h HyB treatment, levels of H2O2 and malondialdehyde, indicators of oxidative stress, were elevated. Detection of H2O2 by 3,3'-diaminobenzidine (DAB) staining suggested that H2O2 could be a marker to efficiently distinguish transgenic and non-transgenic plants. Analysis of 24 segregating progenies of an HPT-containing rice plant by RT-PCR and DAB staining verified that DAB staining is a feasible method for detecting transformants and non-transformants. Transgene-free genome-edited plants were faithfully validated by both PCR and the H2O2-based method. Moreover, HyB induced overproduction of H2O2 in leaves of Arabidopsis, maize, tobacco, and tomato, which suggests the potential application of the DAB method for detecting transgenic events containing HPT in a wide range of plant species. Thus, visual detection of DAB provides a simple, cheap, and reliable way to efficiently identify transgene-free genome-edited and HPT-containing transgenic rice.
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Genoma de Planta , Peróxido de Hidrógeno/análisis , Oryza/genética , Plantas Modificadas Genéticamente/genética , Sistemas CRISPR-Cas , Edición Génica , Fosfotransferasas (Aceptor de Grupo Alcohol)/genética , Proteínas de Plantas/genética , TransgenesRESUMEN
BACKGROUND: Cold stress is the main factor that reduces rice yield in subtropical areas, especially at the seedling stage. Most of the current studies on cold stress focus the responses of rice shoots to cold stress. Limited studies are available on that of rice roots to cold stress. This study aimed to illustrate the biochemical responses of rice root under cold treatment, and subject to the establishment of cold stress-related biochemical traits for rice breeding or cropping-adjustment. RESULTS: Our results showed that the growth of rice seedling diminished under cold stress with difference extents among eight rice cultivars of most productive in Taiwan. Under cold treatments, the tested cultivars with higher growth rate had a higher level of hydrogen peroxide (H2O2) in the shoots but had a lower level in the roots. In contrast, the tested cultivates with low growth rate had higher levels of H2O2 in the roots but a lower level in the shoots. Meanwhile, higher MDA contents and higher cell-damage related electrolyte leakage were also found in the roots not in the shoots, suggesting that cold stress might induce oxidative stress in the roots, not in the shoots. Furthermore, the activity analysis of four antioxidant enzymes, namely superoxide dismutase (SOD), catalase (CAT), ascorbic peroxidase (APX), and glutathione reductase (GR), revealed that cold stress could increase SOD and CAT activities in the roots. CONCLUSIONS: In summary, low H2O2 and low MDA contents along with lower SOD and CAT activities in rice root could be the biochemical traits of cold responses in rice seedlings. The results are hoping to have a contribution to the rice breeding or cropping-adjustment on cold tolerance.
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AIMS: To identify and describe the various patterns of parents' perspectives on avoiding secondhand smoke exposure. DESIGN: Q methodology was applied to investigate the parental perspectives of 50 parents. METHODS: The study was implemented from September-December 2016. Forty-two Q-statements were constructed based on the literature related to parental attitudes and prevention practices regarding preventing young children from experiencing secondhand smoke exposure. A series of Q-sorts was performed by the participants to rank the statements into a Q-sort grid. PQMethod 2.35 software was used to perform principal component analysis to identify different patterns of parents' perspectives. RESULTS: Five patterns of shared perspectives, which accounted for 62% of the total variance, were derived from the analysis: (a) lack of confidence to confront smokers in non-smoking areas; (b) awareness of health hazards but not ready to take preventive actions; (c) emphasis on parental responsibility and behavioural guidance; (d) awareness of health rights protected by legislation; and (e) strong willingness to take protective actions. CONCLUSION: Our findings revealed the shared perspectives of five groups of parents. The exploration of clusters of parents could assist healthcare professionals in acknowledging parents' tendencies related to attitudes and responses towards secondhand smoke exposure. IMPACT: Using a forced distribution through the Q-sorting technique, the particular perspective patterns of parents' experiences would be captured. These findings can serve as a useful guide for researchers and practitioners to develop tailored intervention programs for parents with the purpose of reducing secondhand smoke exposure in young children.
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Exposición a Riesgos Ambientales/prevención & control , Padres/psicología , Contaminación por Humo de Tabaco , Adulto , Niño , Preescolar , Femenino , Humanos , MasculinoRESUMEN
Autonomic dysfunctions including impaired baroreflex sensitivity (BRS) can develop after acute ischemic stroke (AIS) and may predispose patients to subsequent cardiovascular adverse events and serve as potential indicators of long-term mortality. This study aimed to determine the potential short-term prognostic significance of BRS after AIS. All patients admitted to Kaohsiung Veterans General Hospital within 72 h after onset of first-ever AIS between April 2008 and December 2012 were enrolled. Autonomic evaluation with continuous 10-minute monitoring of beat-to-beat hemodynamic and intracranial parameters was performed within 1 week after stroke by using the Task Force Monitor and transcranial Doppler. The 176 enrolled AIS patients were divided into high-BRS and low-BRS groups. All but two enrolled patients (who died within 3 months after stroke) attended scheduled follow-ups. The high-BRS group had significantly lower National Institutes of Health Stroke Scale (NIHSS) scores at 1 and 2 weeks after stroke and at discharge; lower modified Rankin scale (mRS) scores 1, 3, 6, and 12 months after stroke; and lower rates of complications and stroke recurrence compared to the low-BRS group. This study provides novel evidence of the utility of BRS to independently predict outcomes after AIS. Furthermore, modifying BRS may hold potential in future applications as a novel therapeutic strategy for acute stroke.
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BACKGROUND: Altered γ-aminobutyric acid signaling is believed to disrupt the excitation/inhibition balance in the striatum, which may account for the motor symptoms of Huntington's disease. Na-K-2Cl cotransporter-1 is a key molecule that controls γ-aminobutyric acid-ergic signaling. However, the role of Na-K-2Cl cotransporter-1 and efficacy of γ-aminobutyric acid-ergic transmission remain unknown in Huntington's disease. METHODS: We determined the levels of Na-K-2Cl cotransporter-1 in brain tissue from Huntington's disease mice and patients by real-time quantitative polymerase chain reaction, western blot, and immunocytochemistry. Gramicidin-perforated patch-clamp recordings were used to measure the Eγ-aminobutyric acid in striatal brain slices. To inhibit Na-K-2Cl cotransporter-1 activity, R6/2 mice were treated with an intraperitoneal injection of bumetanide or adeno-associated virus-mediated delivery of Na-K-2Cl cotransporter-1 short-hairpin RNA into the striatum. Motor behavior assays were employed. RESULTS: Expression of Na-K-2Cl cotransporter-1 was elevated in the striatum of R6/2 and Hdh150Q/7Q mouse models. An increase in Na-K-2Cl cotransporter-1 transcripts was also found in the caudate nucleus of Huntington's disease patients. Accordingly, a depolarizing shift of Eγ-aminobutyric acid was detected in the striatum of R6/2 mice. Expression of the mutant huntingtin in astrocytes and neuroinflammation were necessary for enhanced expression of Na-K-2Cl cotransporter-1 in HD mice. Notably, pharmacological or genetic inhibition of Na-K-2Cl cotransporter-1 rescued the motor deficits of R6/2 mice. CONCLUSIONS: Our findings demonstrate that aberrant γ-aminobutyric acid-ergic signaling and enhanced Na-K-2Cl cotransporter-1 contribute to the pathogenesis of Huntington's disease and identify a new therapeutic target for the potential rescue of motor dysfunction in patients with Huntington's disease. © 2019 International Parkinson and Movement Disorder Society.
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Núcleo Caudado/metabolismo , Enfermedad de Huntington/metabolismo , Simportadores de Cloruro de Sodio-Potasio/metabolismo , Ácido gamma-Aminobutírico/metabolismo , Animales , Modelos Animales de Enfermedad , Humanos , Ratones , Ratones Transgénicos , Neuronas/metabolismo , Simportadores de Cloruro de Sodio-Potasio/genéticaRESUMEN
Huntington's disease (HD) is an autosomal dominant progressive neurodegenerative disease that is characterized by a triad of motor, psychiatric and cognitive impairments. There is still no effective therapy to delay or halt the disease progress. The striatum and cortex are two particularly affected brain regions that exhibit dense reciprocal excitatory glutamate and inhibitory gamma-amino butyric acid (GABA) connections. Imbalance between excitatory and inhibitory signalling is known to greatly affect motor and cognitive processes. Emerging evidence supports the hypothesis that disrupted GABAergic circuits underlie HD pathogenesis. In the present review, we focused on the multiple defects recently found in the GABAergic inhibitory system, including altered GABA level and synthesis, abnormal subunit composition and distribution of GABAA receptors and aberrant GABAA receptor-mediated signalling. In particular, the important role of cation-chloride cotransporters (i.e. NKCC1 and KCC2) is discussed. Recent studies also suggest that neuroinflammation contributes significantly to the abnormal GABAergic inhibition in HD. Thus, GABAA receptors and cation-chloride cotransporters are potential therapeutic targets for HD. Given the limited availability of therapeutic treatments for HD, a better understanding of GABAergic dysfunction in HD could provide novel therapeutic opportunities.
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Enfermedad de Huntington/metabolismo , Receptores de GABA/metabolismo , Transducción de Señal , Ácido gamma-Aminobutírico/metabolismo , Animales , Descubrimiento de Drogas , Humanos , Enfermedad de Huntington/tratamiento farmacológico , Enfermedad de Huntington/patología , Terapia Molecular Dirigida , Transducción de Señal/efectos de los fármacosRESUMEN
The methionine residues of proteins are the preferred targets of oxidation by reactive oxygen species resulting in the formation of methionine sulfoxide (MetSO), which impairs protein function. Methionine sulfoxide reductase A and B (MSR) catalyze the reduction of the MetSO S and R epimers back to Met residues, respectively. The roles of abscisic acid (ABA) and nitric oxide (NO) on the transcript levels of methionine sulfoxide reductase (MSR; EC 1.8.4.6) in the roots of 2-d-old etiolated rice (Oryza sativa L.) seedlings exposed to NaCl were examined. The OsMSR transcript levels increased upon exposure to NaCl, which increased as the NaCl concentrations increased. Fluridone (Flu) pretreatment inhibited the increases in ABA and NO contents and the OsMSRA4, OsMSRA5, OsMSRB1.1, OsMSRB3 and OsMSRB5 transcripts by NaCl, while ABA application reversed the effects of Flu. Flu did not affect the OsMSRA2 and OsMSRB1.2 transcripts. The application of the NO scavenger, 2-(4-carboxyphenyl)-4,4,5,5,-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), to NaCl-treated roots inhibited the increase in all of the OsMSRs transcripts with the exception of OsMSRB1.2. Treatment with the NO donor sodium nitroprusside (SNP) increased all the OsMSRs transcripts. The inhibitory effect of Flu on the increase of the OsMSRA4, OsMSRA5, OsMSR1.1, OsMSRB 3, and OsMSRB5 transcripts in the NaCl-treated roots was reversed by SNP. cPTIO inhibited the expression of all the OsMSR genes. The OsMSRA2.1 and OsMSRB1.2 transcripts can be increased by SNP. The Flu-inhibited internal ABA contents cannot be recovered by treatment with cPTIO or SNP. In addition, NaCl-induced NO production can be divided into ABA-dependent and ABA-independent routes. Therefore, the ABA-dependent NO route regulated the expression of OsMSRA4, OsMSRA5, OsMSRB1.1, OsMSRB 3, and OsMSRB5 in the NaCl-treated rice roots, while the ABA-independent NO pathway modulated OsMSRA2.1, and the ABA-independent and NO-independent pathway modulated OsMSRB1.2 expression in response to NaCl treatment.