RESUMEN
Lens gap junctions (GJs) formed by Cx46 and Cx50 are important to keep lens transparency. Functional studies on Cx46 and Cx50 GJs showed that the Vj-gating, single channel conductance (γj), gating polarity, and/or channel open stability could be modified by the charged residues in the amino terminal (NT) domain. The role of hydrophobic residues in the NT on GJ properties is not clear. Crystal and cryo-EM GJ structures have been resolved, but the NT domain structure has either not been resolved or has showed very different orientations depending on the component connexins and possibly other experimental conditions, making it difficult to understand the structural basis of the NT in Vj-gating and γj. Here, we generated missense variants in Cx46 and Cx50 NT domains and studied their properties by recombinant expression and dual whole-cell patch clamp experiments on connexin-deficient N2A cells. The NT variants (Cx46 L10I, N13E, A14V, Q15N, and Cx50 I10L, E13N, V14A, N15Q) were all able to form functional GJs with similar coupling%, except Cx46 N13E, which showed a significantly reduced coupling%. The GJs of Cx46 N13E, A14V and Cx50 E13N, N15Q showed a reduced coupling conductance. Vj-gating of all the variant GJs were similar to the corresponding wild-type GJs except Cx46 L10I. The γj of Cx46 N13E, A14V, Cx50 E13N, and N15Q GJs was reduced to 51%, 82%, 87%, and 74%, respectively, as compared to their wild-type γjs. Structural models of Cx46 L10I and A14V predicted steric clashes between these residues and the TM2 residues, which might be partially responsible for our observed changes in GJ properties. To verify the importance of hydrophobic interactions, we generated a variant, Cx50 S89T, which also shows a steric clash and failed to form a functional GJ. Our experimental results and structure models indicate that hydrophobic interactions between the NT and TM2 domain are important for their Vj-gating, γj, and channel open stability in these and possibly other GJs.
Asunto(s)
Uniones Comunicantes , Activación del Canal Iónico , Conexinas/metabolismo , Uniones Comunicantes/genética , Uniones Comunicantes/metabolismo , Interacciones Hidrofóbicas e Hidrofílicas , Canales Iónicos/metabolismoRESUMEN
OBJECTIVES: The purpose of this study was to describe the services provided by community pharmacists and their confidence in providing advice on self-medication for women during pregnancy and breastfeeding. METHODS: A cross-sectional, questionnaire-based study was distributed online to community pharmacists across Jordan in the period from August through December 2020. The questionnaire identified the services most frequently offered to women throughout pregnancy or breastfeeding and evaluated the community pharmacists' confidence in providing advice on self-medication and other services for this population group. KEY FINDINGS: A total of 340 community pharmacists completed the questionnaire. Most of them were female (89.4%), and just over half (55%) had less than 5 years of experience. The services offered by community pharmacists to women throughout pregnancy were dispensing medicine (49.1%), and dispensing herbal products (48.5%), whereas the services mainly provided for women during breastfeeding were providing advice on contraception (71.5%), and dispensing medication (45.3%).The most frequent complaints reported by women during pregnancy were gastrointestinal and urinary symptoms, and for women during lactation low milk supply and contraception. Regarding pharmacists' confidence in providing advice on self-medication, nearly half of the respondents (50% and 49.7%) reported that they had confidence in solving medication and health challenges during pregnancy and breastfeeding, respectively. CONCLUSION: Although community pharmacists provided different services for women who were pregnant or breastfeeding, many did not feel confident handling them. Continuous training programs are required to enhance community pharmacists' ability to provide adequate care for women during pregnancy and breastfeeding.
Asunto(s)
Lactancia Materna , Servicios Comunitarios de Farmacia , Servicios de Salud , Femenino , Humanos , Masculino , Embarazo , Estudios Transversales , Jordania , FarmacéuticosRESUMEN
Objectives: Resident physicians are particularly prone to sleep disturbance due to long shift hours and excessive workload. Despite the numerous measures undertaken to improve their wellbeing, it is still unknown if limiting the work shift duration would improve sleep quality. We sought to compare sleep quality, anxiety, and depression before and after implementing duty hour limits. We also aim to evaluate how satisfaction with life is related to sleep quality, anxiety, and depression. Methods: We used a self-reported questionnaire to obtain data about sleep quality, anxiety, and depression using the Pittsburgh Sleep Quality Index and Patient Health Questionnaire-4 (PHQ-4) scales, respectively. Using data from a previous study, we compared those parameters before and after implementing duty hour reduction across several specialties at King Abdullah University Hospital, Jordan. Furthermore, we investigated residents' life satisfaction using the Satisfaction with Life Scale. Results: One hundred and eighty residents filled the questionnaire (median age = 26.5 years). Males reported higher rates of poor sleep quality while females had higher rates of anxiety and depression. Decreasing the duration of on-call shifts from 32 to 24 hours decreased the prevalence of poor sleep quality from 91.5% to 83.2% (p = 0.038), and smoking rates decreased from 30.4% to 12.5% (p < 0.001). More than six on-calls per month were associated with poorer quality of sleep. Night float shifts significantly decreased rates of moderate and severe PHQ-4 scores (p < 0.001). In addition, 63.3% of residents were satisfied with life. Life satisfaction was associated with enhanced sleep quality and lower PHQ-4 scores (p = 0.007 and p < 0.001, respectively). Conclusions: Optimizing shift scheduling and duration can positively influence rates of sleep quality, anxiety, depression, and smoking. More interventions should be tackled along with duty hour limits to optimize residents' life satisfaction.
RESUMEN
OBJECTIVES: Shift work is defined as any irregular work schedule that extends beyond the usual 9 am to 5 pm time frame. Evidence from outside medicine suggests that it may be related to detrimental health outcomes. Our objective from this study is to evaluate sleep quality, health risks, and chronic diseases among post-graduate resident physicians who work on rotating shifts at a large tertiary health care center. STUDY DESIGN: A self-reported questionnaire-based cross-sectional study. METHODS: Sleep quality was assessed by Pittsburgh Sleep Quality Index (PSQI) while anxiety and depression were estimated through the four-item patient health questionnaire for anxiety and depression (PHQ-4). Associations between sleep quality and the following: Gender, PHQ-4 stage, year of residency, number of on-calls per month and subjective fatigue; memory impairment; and lack of concentration was investigated. RESULTS: A total of 201 resident physicians participated in the study [60.7% males, median; IQR age: 27 years (26-29). More than one third of subjects were smokers, 41.3% were overweight, and 16.4% were obese. The majority (90%) reported poor sleep quality, 38.3% mild PHQ-4, 21.4% moderate PHQ-4, and 18.9% severe PHQ-4. Residents having six on-calls or more per month had significantly poorer sleep quality (p: 0.03), as well as higher anxiety and depression scores compared to their counterparts. Poor sleep quality was markedly associated with moderate PHQ-4, subjective fatigue, and lack of concentration (p: 0.026, 0.004 and 0.001, respectively). Subjective difficulty with concentration was reported in 86.6% of resident physicians and was significantly higher as the number of on-calls per month is 3 or more. Most residents report subjective fatigue (92.5%) while subjective memory impairment was prevalent in 68.7%. Irritable bowel syndrome was the most prevalent chronic disorder (13%), followed by heartburn or gastrointestinal ulcers and disc prolapse (6% and 3.5%, respectively). CONCLUSIONS: Resident physicians have considerable risk for developing severe diseases. Our findings suggest that several modifications should be undertaken to enhance work facilities, limit working hours, and raise awareness among post-graduate resident physicians.
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Fatiga/psicología , Estado de Salud , Internado y Residencia , Médicos/estadística & datos numéricos , Horario de Trabajo por Turnos , Sueño/fisiología , Adulto , Ansiedad/psicología , Estudios Transversales , Depresión/psicología , Educación de Postgrado en Medicina , Femenino , Humanos , Masculino , Autoinforme , Encuestas y Cuestionarios , Tolerancia al Trabajo ProgramadoRESUMEN
OBJECTIVE: Intracranial hemorrhage is a critical medical emergency. Nosocomial infections may promote worse outcomes in these vulnerable patients. This study investigated microbial features, predictors, and clinical outcomes of nosocomial infections among patients with multiple subtypes of intracranial hemorrhage. PATIENTS AND METHODS: We conducted a retrospective cohort study of patients that were hospitalized with intracranial hemorrhage between January 2015 and October 2018, and divided them into two groups based on the development of nosocomial infection. Within the cohort of patients with nosocomial infections, microbiology and resistance patterns were established across multiple sites of infection. Moreover, consequences of nosocomial infection such as mortality and length of hospital stay were determined. RESULTS: A total of 233 cases were identified that met our inclusion and exclusion criteria out of which were 94 cases of nosocomial infection (40.3%) versus 139 cases with no nosocomial infection (59.7%). The most common infections were pneumonia, urinary tract infections, and bacteremia. Resistance accounted for 70.2% of cultures. Multivariable analysis revealed significant association of nosocomial infections with hypertension (OR: 2.62, 95% CI: 1.11-6.16, p = 0.027), hospital LOS (OR: 1.08, 95% CI: 1.05-1.12, p < 0.001), levetiracetam (OR: 3.6, 95% CI: 1.41-0.922, p = 0.007), and GCS category (OR: 5.42, 95% CI: 1.67-17.55, p = 0.005 and OR: 7.63, 95% CI: 2.44-23.87, p < 0.001 for moderate and severe, respectively). Patients with nosocomial infections witnessed a significant increase in the length of hospital stay (23 versus 8 hospital days, p < 0.001). This finding was significant across most types of brain hemorrhage. Mortality was significantly associated with GCS category (OR: 10.1, 95% CI: 4-25.7, p < 0.001) and percutaneous endoscopic gastrostomy tube insertion (OR: 19.6, 95% CI: 4.1-91, p < 0.001). CONCLUSIONS: Collectively, these findings suggest that nosocomial infections are common among patients with intracranial hemorrhage and can be predictable by considering certain risk factors. Future studies are warranted to evaluate the efficacy of implementing infection control strategies or protocols on these patients to achieve better therapeutic outcomes.