Inhibitory interneurons regulate the oscillatory rhythms and network synchrony that are required for cognitive functions and disrupted in Alzheimer's disease (AD). Network dysrhythmias in AD and multiple neuropsychiatric disorders are associated with hypofunction of Nav1.1, a voltage-gated sodium channel subunit predominantly expressed in interneurons. We show that Nav1.1-overexpressing, but not wild-type, interneuron transplants derived from the embryonic medial ganglionic eminence (MGE) enhance behavior-dependent gamma oscillatory activity, reduce network hypersynchrony, and improve cognitive functions in human amyloid precursor protein (hAPP)-transgenic mice, which simulate key aspects of AD. Increased Nav1.1 levels accelerated action potential kinetics of transplanted fast-spiking and non-fast-spiking interneurons. Nav1.1-deficient interneuron transplants were sufficient to cause behavioral abnormalities in wild-type mice. We conclude that the efficacy of interneuron transplantation and the function of transplanted cells in an AD-relevant context depend on their Nav1.1 levels. Disease-specific molecular optimization of cell transplants may be required to ensure therapeutic benefits in different conditions.
BackgroundThe World health Organization (WHO) declares dengue and dengue hemorrhagic fever to be endemic in South Asia. Despite the magnitude of problem, no documented evidence exists in Pakistan which reveals the awareness and practices of the country's adult population regarding dengue fever, its spread, symptoms, treatment and prevention. This study was conducted to assess the level of knowledge, attitudes and practices regarding dengue fever in people visiting tertiary care hospitals in Karachi, Pakistan.MethodsA cross-sectional pilot study was conducted among people visiting tertiary care hospitals in Karachi. Through convenience sampling, a pre-tested and structured questionnaire was administered through a face-to-face unprompted interview with 447 visitors. Knowledge was recorded on a scale of 1–3.ResultsAbout 89.9% of individuals interviewed had heard of dengue fever. Sufficient knowledge about dengue was found to be in 38.5% of the sample, with 66% of these in Aga Khan University Hospital and 33% in Civil Hospital Karachi. Literate individuals were relatively more well-informed about dengue fever as compared to the illiterate people (p<0.001). Knowledge based upon preventive measures was found to be predominantly focused towards prevention of mosquito bites (78.3%) rather than eradication of mosquito population (17.3%). Use of anti- mosquito spray was the most prevalent (48.1%) preventive measure. Television was considered as the most important and useful source of information on the disease.ConclusionAdult population of Karachi has adequate knowledge related to the disease ‘dengue’ on isolated aspects, but the overall prevalence of ‘sufficient knowledge’ based on our criteria is poor. We demonstrated adequate prevalence of preventive practices against the disease. Further studies correlating the association between knowledge and its effectiveness against dengue will be helpful in demonstrating the implications of awareness campaigns.
Highlights d AD and DS mice display aberrant 12-to 20-Hz oscillations associated with epileptic spikes d GluN2A-NMDAR enhancement reduces aberrant oscillations and spikes in AD and DS mice d Chronic GluN2A-NMDAR activation improves cognitive functions in AD and DS mice d GluN2A PAMs could benefit brain disorders with hypersynchrony and cognitive deficits
Purpose Adequate knowledge, positive attitude, and proper practice of personal protective equipment by healthcare workers are necessary to get protection from COVID-19 infection. But this area is yet to be explored. Hence, we aimed to assess the knowledge, attitude, and practice (KAP) regarding personal protective equipment (PPE) among healthcare workers, along with a survey of the possible determinants. Subjects and Methods For this cross-sectional study, online and offline surveys were conducted among a sample of 393 healthcare workers from five different districts of Bangladesh. A validated self-administered questionnaire comprising five sections (socio-demography, work-related information, knowledge, attitude, and practice) was used for data collection. Multivariate stepwise forward logistic regression was applied to find significant factors associated with good attitude, and practice using SPSS version 25. Results The average age of the 393 participants was 28.9±5.2 years with a male-female ratio of one. Of them, 99.5% (n=391) had good knowledge, 88.8% (n=349) had positive attitude and 51.7% (n=203) had good practice regarding PPE. Results revealed that being a physician and living at home were significantly associated with a positive attitude. While being a non-physician, having lower education, working in private hospitals, and using office transport were associated with good practice regarding PPE. Conclusion The findings demonstrated that the healthcare workers had an overall good knowledge and a positive attitude but a poor practice regarding PPE. This study also highlighted the factors influencing KAP towards PPE that must be addressed in future education, awareness, and counseling programs.
Staphylococcus aureus is an increasing problem in clinical practice because of reduced susceptibility to available antibiotics. The objective of the study was to determine the frequency of Methicillin-resistant S.aureus (MRSA) in Peshawar, Pakistan. Clinical isolates of S. aureus were subjected to determination of antibiotic resistance, MICs and inducible clindamycin resistance (ICR). Out of total 280 S. aureus isolates, the frequency of MRSA was 36.1 % (n = 101). MRSA infection was found higher among the age group 50–59 years (60.71 %, OR 3.09), followed by 20–29 years (47.5 %, OR 1.74). Frequency of MRSA in female and male was 39.8 and 34 % respectively. MRSA was more frequent in blood specimens (48.7 %, OR 2.14). The frequency of community and hospital acquired MRSA was 42 and 34.8 % respectively. MRSA showed high resistance (100 %) to penicillin and cefoxitin followed by erythromycin (99 %). While MRSA exhibited 100 % susceptibility to vancomycin and linezolid. We have also found 7 vancomycin intermediate sensitive S. aureus (VISA) isolates. ICR was observed in 15.84 % (n = 16) of MRSA isolates. It is concluded that MRSA is potential threat to public health in Peshawar. Vancomycin and linezolid could be prescribed as a drug of choice in treating MRSA associated infections. In addition, ICR should be routinely checked to avoid clindamycin treatment failure.
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