CB1R-Mediated Activation of Caspase-3 Causes Epigenetic and Neurobehavioral Abnormalities in Postnatal Ethanol-Exposed Mice

Alcohol exposure can affect brain development, leading to long-lasting behavioral problems, including cognitive impairment, which together is defined as fetal alcohol spectrum disorder (FASD). However, the fundamental mechanisms through which this occurs are largely unknown. In this study, we report that the exposure of postnatal day 7 (P7) mice to ethanol activates caspase-3 via cannabinoid receptor type-1 (CB1R) in neonatal mice and causes a reduction in methylated DNA binding protein (MeCP2) levels. The developmental expression of MeCP2 in mice is closely correlated with synaptogenesis and neuronal maturation. It was shown that ethanol treatment of P7 mice enhanced Mecp2 mRNA levels but reduced protein levels. The genetic deletion of CB1R prevented, and administration of a CB1R antagonist before ethanol treatment of P7 mice inhibited caspase-3 activation. Additionally, it reversed the loss of MeCP2 protein, cAMP response element binding protein (CREB) activation, and activity-regulated cytoskeleton-associated protein (Arc) expression. The inhibition of caspase-3 activity prior to ethanol administration prevented ethanol-induced loss of MeCP2, CREB activation, epigenetic regulation of Arc expression, long-term potentiation (LTP), spatial memory deficits and activity-dependent impairment of several signaling molecules, including MeCP2, in adult mice. Collectively, these results reveal that the ethanol-induced CB1R-mediated activation of caspase-3 degrades the MeCP2 protein in the P7 mouse brain and causes long-lasting neurobehavioral deficits in adult mice. This CB1R-mediated instability of MeCP2 during active synaptic maturation may disrupt synaptic circuit maturation and lead to neurobehavioral abnormalities, as observed in this animal model of FASD

High energy X-γ ray spectrometer on the Chandrayaan-1 mission to the Moon

The Chandrayaan-1 mission to the Moon scheduled for launch in late 2007 will include a high energy X-ray spectrometer (HEX) for detection of naturally occurring emissions from the lunar surface due to radioactive decay of the 238U and 232Th series nuclides in the energy region 20-250 keV. The primary science objective is to study the transport of volatiles on the lunar surface by detection of the 46.5 keV line from radioactive 210Pb, a decay product of the gaseous 222Rn, both of which are members of the 238U decay series. Mapping of U and Th concentration over the lunar surface, particularly in the polar and U-Th rich regions will also be attempted through detection of prominent lines from the U and Th decay series in the above energy range. The low signal strengths of these emissions require a detector with high sensitivity and good energy resolution. Pixelated Cadmium-Zinc-Telluride (CZT) array detectors having these characteristics will be used in this experiment. Here we describe the science considerations that led to this experiment, anticipated flux and background (lunar continuum), the choice of detectors, the proposed payload configuration and plans for its realizatio

Etiological Profile and Treatment Outcome of Epistaxis at a Tertiary Care Hospital in Northwestern Tanzania: A Prospective Review of 104 Cases.

Epistaxis is the commonest otolaryngological emergency affecting up to 60% of the population in their lifetime, with 6% requiring medical attention. There is paucity of published data regarding the management of epistaxis in Tanzania, especially the study area. This study was conducted to describe the etiological profile and treatment outcome of epistaxis at Bugando Medical Centre, a tertiary care hospital in Northwestern Tanzania. This was a prospective descriptive study of the cases of epistaxis managed at Bugando Medical Centre from January 2008 to December 2010. Data collected were analyzed using SPSS computer software version 15. A total of 104 patients with epistaxis were studied. Males were affected twice more than the females (2.7:1). Their mean age was 32.24 ± 12.54 years (range 4 to 82 years). The modal age group was 31-40 years. The commonest cause of epistaxis was trauma (30.8%) followed by idiopathic (26.9%) and hypertension (17.3%). Anterior nasal bleeding was noted in majority of the patients (88.7%). Non surgical measures such as observation alone (40.4%) and anterior nasal packing (38.5%) were the main intervention methods in 98.1% of cases. Surgical measures mainly intranasal tumor resection was carried out in 1.9% of cases. Arterial ligation and endovascular embolization were not performed. Complication rate was 3.8%. The overall mean of hospital stay was 7.2 ± 1.6 days (range 1 to 24 days). Five patients died giving a mortality rate of 4.8%. Trauma resulting from road traffic crush (RTC) remains the most common etiological factor for epistaxis in our setting. Most cases were successfully managed with conservative (non-surgical) treatment alone and surgical intervention with its potential complications may not be necessary in most cases and should be the last resort. Reducing the incidence of trauma from RTC will reduce the incidence of emergency epistaxis in our centre

Inferior alveolar nerve injury with laryngeal mask airway: a case report

<p>Abstract</p> <p>Introduction</p> <p>The incidence of damage to the individual cranial nerves and their branches associated with laryngeal mask airway use is low; there have been case reports of damage to the lingual nerve, hypoglossal nerve and recurrent laryngeal nerve. To the best of our knowledge we present the first reported case of inferior alveolar nerve injury associated with laryngeal mask airway use.</p> <p>Case presentation</p> <p>A 35-year-old Caucasian man presented to our facility for elective anterior cruciate ligament repair. He had no background history of any significant medical problems. He opted for general anesthesia over a regional technique. He was induced with fentanyl and propofol and a size 4 laryngeal mask airway was inserted without any problems. His head was in a neutral position during the surgery. After surgery in the recovery room, he complained of numbness in his lower lip. He also developed extensive scabbing of the lower lip on the second day after surgery. The numbness and scabbing started improving after a week, with complete recovery after two weeks.</p> <p>Conclusion</p> <p>We report the first case of vascular occlusion and injury to the inferior alveolar nerve, causing scabbing and numbness of the lower lip, resulting from laryngeal mask airway use. This is an original case report mostly of interest for anesthetists who use the laryngeal mask airway in day-to-day practice. Excessive inflation of the laryngeal mask airway cuff could have led to this complication. Despite the low incidence of cranial nerve injury associated with the use of the laryngeal mask airway, vigilant adherence to evidence-based medicine techniques and recommendations from the manufacturer's instructions can prevent such complications.</p

Protective and Enhancing HLA Alleles, HLA-DRB1*0901 and HLA-A*24, for Severe Forms of Dengue Virus Infection, Dengue Hemorrhagic Fever and Dengue Shock Syndrome

Dengue has become one of the most common viral diseases transmitted by infected mosquitoes (with any of the four dengue virus serotypes: DEN-1, -2, -3, or -4). It may present as asymptomatic or illness, ranging from mild to severe disease. Recently, the severe forms, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS), have become the leading cause of death among children in Southern Vietnam. The pathogenesis of DHF/DSS, however, is not yet completely understood. The immune response, virus virulence, and host genetic background are considered to be risk factors contributing to disease severity. Human leucocyte antigens (HLA) expressed on the cell surface function as antigen presenting molecules and those polymorphism can change individuals' immune response. We investigated the HLA-A, -B (class I), and -DRB1 (class II) polymorphism in Vietnamese children with different severity (DHF/DSS) by a hospital-based case-control study. The study showed persons carrying HLA-A*2402/03/10 are about 2 times more likely to have severe dengue infection than others. On the other hand, HLA-DRB1*0901 persons are less likely to develop DSS with DEN-2 virus infection. These results clearly demonstrated that HLA controlled the susceptibility to severe forms of DV infection

Patients' perceived needs of osteoarthritis health information: A systematic scoping review

Background: Optimal management of osteoarthritis requires active patient participation. Understanding patients’ perceived health information needs is important in order to optimize health service delivery and health outcomes in osteoarthritis. We aimed to review the existing literature regarding patients’ perceived health information needs for OA. Methods: A systematic scoping review was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990–2016). Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Aggregates of patients’ perceived needs of osteoarthritis health information were categorized. Results: 30 studies from 2876 were included: 16 qualitative, 11 quantitative and 3 mixed-methods studies. Three areas of perceived need emerged: (1) Need for clear communication: terms used were misunderstood or had unintended connotations. Patients wanted clear explanations. (2) Need for information from various sources: patients wanted accessible health professionals with specialist knowledge of arthritis. The Internet, whilst a source of information, was acknowledged to have dubious reliability. Print media, television, support groups, family and friends were utilised to fulfil diverse information needs. (3) Needs of information content: patients desired more information about diagnosis, prognosis, management and prevention. Conclusions: Patients desire more information regarding the diagnosis of osteoarthritis, its impact on daily life and its long-term prognosis. They want more information not only about pharmacological management options, but also non-pharmacological options to help them manage their symptoms. Also, patients wanted this information to be delivered in a clear manner from multiple sources of health information. To address these gaps, more effective communication strategies are required. The use of a variety of sources and modes of delivery may enable the provision of complementary material to provide information more successfully, resulting in better patient adherence to guidelines and improved health outcomes