The involvement of SigmaR1K142 degradation mediated by ERAD in neural senescence linked with CdCl2 exposure.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Due to its uncertain pathogenesis, there is currently no treatment available for AD. Increasing evidences have linked cellular senescence to AD, although the mechanism triggering cellular senescence in AD requires further exploration. To investigate the involvement of cellular senescence in AD, we explored the effects of cadmium chloride (CdCl2) exposure, one of the potential environmental risk factors for AD, on neuron senescence in vivo and in vitro. ß-amyloid (Aß) and tubulin-associated protein (tau) pathologies were found to be enhanced by CdCl2 exposure in the in vitro models, while p53/p21/Rb cascade-related neuronal senescence pathways were activated. Conversely, the use of melatonin, a cellular senescence inhibitor, or a cadmium ion chelator suppressed CdCl2-induced neuron senescence, along with the Aß and tau pathologies. Mechanistically, CdCl2 exposure activated the suppressor enhancer Lin-12/Notch 1-like (SEL1L)/HMG-CoA reductase degradation 1 (HRD1)-regulated endoplasmic reticulum-associated degradation (ERAD), which enhanced the ubiquitin degradation of sigma-1 receptor (SigmaR1) by specifically recognizing its K142 site, resulting in the activation of the p53/p21/Rb pathway via the induction of Ca2+ dyshomeostasis and mitochondrial dysfunction. In the in vivo models, the administration of the SigmaR1 agonist ANAVEX2-73 rescues neurobehavioral inhibition and alleviates cellular senescence and AD-like pathology in the brain tissue of CdCl2-exposed mice. Consequently, the present study revealed a novel senescence-associated regulatory route for the SEL1L/HRD1/SigmaR1 axis that affects the pathological progression of CdCl2 exposure-associated AD. CdCl2 exposure activated SEL1L/HRD1-mediated ERAD and promoted the ubiquitinated degradation of SigmaR1, activating p53/p21/Rb pathway-regulated neuronal senescence. The results of the present study suggest that SigmaR1 may function as a neuroprotective biomarker of neuronal senescence, and pharmacological activation of SigmaR1 could be a promising intervention strategy for AD therapy.

Rab7a-mTORC1 signaling-mediated cholesterol trafficking from the lysosome to mitochondria ameliorates hepatic lipotoxicity induced by aflatoxin B1 exposure.

Aflatoxin B1 (AFB1) is a common contaminant in many foodstuffs and is considered a public health concern worldwide due to its hepatotoxicity caused by lipid metabolism disorders. However, the molecular mechanism underlying AFB1-induced lipotoxicity-dependent liver injury via regulating cholesterol metabolism remains unclear. We established a cholesterol trafficking disorder-mediated hepatic lipotoxicity model with AFB1 mixture exposure in vitro (HepaRG and HepG2 cells, 1.6 µM for 36 h) and in vivo (C57BL/6 mice, 3 mg kg-1, i.g., every other day for 6 weeks). In vitro, the interaction between lysosomal Niemann-Pick type C1 (NPC1) protein and mitochondrial translocator protein (TSPO) regulated lipotoxicity induced by AFB1 mixture exposure, including lysosomal membrane permeabilization and mitochondria-dependent necroptosis. Moreover, the downregulation of lysosomal Ras-associated protein 7a (Rab7a) enhanced the mammalian target of rapamycin complex 1 (mTORC1)-mediated disorders of cholesterol trafficking from the lysosome to mitochondria. Furthermore, cholesterol trafficking disorder-mediated hepatic lipotoxicity induced by the low-dose level of AFB1 exposure was relieved by genetic or pharmaceutic activation of Rab7a to inhibit mTORC1 in vitro and ex vivo. In vivo, mTORC1 inhibitor (Torin1, 4 mg kg-1, i.p., every other day for 3 weeks) alleviated the cholesterol trafficking disorder-mediated hepatic lipotoxicity via upregulating the molecular machinery of lysosomes and mitochondria contact mediated by NPC1 and TSPO interaction in the low dose of AFB1 exposure. Altogether, our data suggested a novel mechanism that lysosomal Rab7a-mTORC1 signaling determined the cholesterol trafficking regulated by NPC1-TSPO from the lysosome to mitochondria, which promoted hepatic lipotoxicity via lysosomal quality control and mitochondria-dependent necroptosis signaling pathways in chemical mixture exposure.

Progress in neurosurgery: Contributions of women neurosurgeons in Asia and Australasia.

At the end of the first 100 years of neurosurgery as a specialty, it is appropriate to look back and then imagine the future. As neurosurgery celebrates its first century, the increasing role of women neurosurgeons is a major theme. This article documents the early women pioneers in neurosurgery in Asia and Australasia. The contributions of these trailblazers to the origins, academics, and professional organizations of neurosurgery are highlighted. The first woman neurosurgeon of the region, Dr. T.S. Kanaka of India, completed her training in 1968, not long after the trailblazers in Europe and North America. She heralded the vibrant communities of neurosurgical women that have developed in the vast and diverse nations of the region, and the many formal and informal groups of women in neurosurgery that have introduced and promoted talented women in the profession. Contributions of women neurosurgeons to academic medicine and society as a whole are briefly highlighted, as are their challenges in this male-dominated specialty. The region is home to many deeply conservative societies; in fact, some nations in the region have not yet trained their first woman neurosurgeon. The fortitude of these individuals to achieve at the highest levels of neurosurgery indicates great potential for future growth of women in the profession, but also demonstrates the need for initiatives and advocacy to reach the full potential of gender equity.

Human resources of hemodialysis centers in Beijing: a cross-sectional survey / 中国实用护理杂志

Objective:To understand the current situation of human resources in the hemodialysis centers of different levels of hospitals in Beijing, and to provide reference data for themedical institutions at all levels to adjust the related human resources programs.Methods:Based on the self-designed questionnaire, the basic situation of 123 hemodialysis centers and the allocation of human resources of doctors, nurses and engineers in medical institutions of Beijing were investigated and analyzed.Results:Each nurse in hemodialysis center was responsible for (4.98± 0.74) hemodialysis patients at the same time in each treatment shift. The specialized nurses accounted for 23.32% of the total registered nurses. The ratio of engineers to dialysis machines was 1∶25.76. The proportion of doctors, nurses and engineers with intermediate professional titles or above was 82.47%, 33.08% and 29.81% respectively. The proportion of doctors with graduate education or above was 51.13%. The proportion of nurses and engineers with bachelor degree or above was 56.12% and 51.56% respectively. The differences in the professional titles and the highest academic qualifications of the employees (doctors, nurses and engineers) between tertiary hospitals and non-tertiary hospitals were statistically significant ( P < 0.05). Conclusion:The number of personnel in Beijing hemodialysis centers is basically in a similar proportion, but there are some differences between the hemodialysis centers of tertiary hospitals and those of non-tertiary hospitals in terms of age composition, working years, professional titles and educational background. It is necessary to optimize the allocation of human resources in hemodialysis centers of different levels of hospitals, further strengthen the training of professional talents and the cooperation of multidisciplinary teams, to promote the sustainable development of medical service quality.

Traumatic Brain Injury in Myanmar: Preliminary Results and Development of an Adjunct Electronic Medical Record.

BACKGROUND: The treatment of traumatic brain injury (TBI) in Myanmar is a major health issue. Comprehensive appreciation of the pathology is limited given the lack of granular metadata available. In this proof-of-concept study, we analyzed demographic data on TBI generated from a novel, prospective, online database in a lower-middle income country. METHODS: Neurosurgery residents were given an electronic tablet for data entry into an online database. Metadata-driven data capture was carried out prospectively by trained residents, and the information was reviewed weekly by the supervising team in the United States. RESULTS: Complete data were available on 242/253 (96%) patients. Age at admission was 37 years (range 16-85), and length of stay was 3.53 days (1-21). Etiologies included motorcycle accidents, falls, assaults, pedestrian vehicular injuries, and industrial accidents. Dispositions were primarily to home (211). Average Glasgow Coma Scale score at admission was 12.97. There was a 68% mortality rate of patients directly admitted to the North Okkalappa General and Teaching Hospital with a Glasgow Coma Scale score <8 versus 75% for patients transferred in from other facilities. Surgery was performed on 30 patients (12.4%). CONCLUSIONS: Despite a lack of formal training in electronic medical records or research, the resident team was able to capture the majority of admissions with granular-level data. This helped shed light on the etiology and severity of TBI in Myanmar. As a result, more effective transport systems and access to trauma care must be achieved. Accessible regional trauma centers with investment in intensive care units, operative care, anesthesia, and imaging resources are necessary.

Arthroscopic Wafer Procedure Versus Ulnar Shortening Osteotomy as a Surgical Treatment for Idiopathic Ulnar Impaction Syndrome.

PURPOSE: To compare clinical and radiologic outcomes and complication rates of the arthroscopic wafer procedure (AWP) and ulnar shortening osteotomy (USO) for idiopathic ulnar impaction syndrome (UIS). METHODS: From May 2009 to June 2014, 42 patients who were aged 45 years or older with idiopathic UIS underwent either the AWP or USO under the following identical surgical indications: (1) less than 4 mm of positive ulnar variance, (2) Palmer classification 2C or 2D lesion of the triangular fibrocartilage complex, (3) stable distal radioulnar joint (DRUJ) and/or lunotriquetral joint, and (4) no evidence of osteoarthritis of the DRUJ or ulnocarpal joint. The patient assignment was not randomized. Were used a visual analog scale for ulnar wrist pain; grip strength; range of motion; the Mayo Wrist Score (MWS); and the Disabilities of the Arm, Shoulder and Hand (DASH) score at 3, 6, 12, and 24 months after surgery to compare clinical outcomes. Ulnar variance, cystic changes of the lunate and triquetrum, and DRUJ arthritis on radiographs and operation-related complications were compared. RESULTS: This study evaluated 19 patients after the AWP and 23 patients after USO. At 3 months, the AWP produced significantly better outcomes than USO regarding grip strength (79.6% ± 14.3% vs 62.7% ± 12.6%, P < .001), MWS (81.8 ± 7.9 points vs 71.3 ± 14.2 points, P = .005), and DASH score (19.4 ± 8.4 vs 31.5 ± 14.0, P = .001); clinical outcomes were similar at 6, 12, and 24 months. The complication rates were 34.8% for USO and 10.5% for the AWP; complications included DRUJ arthritis (n = 4), implant irritation (n = 6), and refracture after implant removal (n = 2) in the USO group and secondary surgery (n = 1) and tendinopathy (n = 1) in the AWP group. CONCLUSIONS: The AWP and USO for idiopathic UIS with subtle positive ulnar variance achieved similar clinical and radiologic outcomes at 2 years after surgery. However, compared with USO, the AWP showed lower complication rates and better grip strength, MWS values, and DASH scores at 3 months after surgery. LEVEL OF EVIDENCE: Level III, comparative trial.

Direct synthesis of solvent-free multiwall carbon nanotubes/silica nonionic nanofluid hybrid material.

The solvent-free nonionic nanofluid hybrid material consisting of multiwall carbon nanotubes (MWNTs) and silica nanoparticles is prepared by a facile route. The content of MWNTs/silica nanoparticles is up to 31 wt %. The hybrid material exhibits liquid-like behavior in the absence of solvent at 45 degrees C, which is a wax solid at room temperature. The process of melting and solidification is reversible over many cycles.

Nursing Management of Hospital Infection Control in Center of Blood Purification / 中华医院感染学杂志

OBJECTIVE To explore the nursing management to control hospital infection in center of the blood purification,and to improve the nursing quality.METHODS All of the nursing management measure,education and strictly administered disinfection and isolation measure were established to control the hospital infection.RESULTS After the nursing management to control hospital infection was standardized and regularted and the standardized sterilization and isolation were set up,the rate of hospital infection was decreased.CONCLUSIONS Nursing management can play a main and key role in the control of hospital infection in center of the blood purification.