Cochranebauer4875

Aberrant accumulation of protein aggregates is a pathological hallmark of many neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). Although a buildup of protein aggregates frequently leads to cell death, whether it is the key pathogenic factor in driving neurodegenerative disease remains controversial. HDAC6, a cytosolic ubiquitin-binding deacetylase, has emerged as an important regulator of ubiquitin-dependent quality control autophagy, a lysosome-dependent degradative system responsible for the disposal of misfolded protein aggregates and damaged organelles. Here, we show that in cell models HDAC6 plays a protective role against multiple disease-associated and aggregation-prone cytosolic proteins by facilitating their degradation. We further show that HDAC6 is required for efficient localization of lysosomes to protein aggregates, indicating that lysosome targeting to autophagic substrates is regulated. Supporting a critical role of HDAC6 in protein aggregate disposal in vivo, genetic ablation of HDAC6 in a transgenic SOD1G93A mouse, a model of ALS, leads to dramatic accumulation of ubiquitinated SOD1G93A protein aggregates. Surprisingly, despite a robust buildup of SOD1G93A aggregates, deletion of HDAC6 only moderately modified the motor phenotypes. These findings indicate that SOD1G93A aggregation is not the only determining factor to drive neurodegeneration in ALS, and that HDAC6 likely modulates neurodegeneration through additional mechanisms beyond protein aggregate clearance.An endo-β-1,4-glucanase gene, cel7A, was cloned from the thermophilic cellulase-producing fungus Neosartorya fischeri P1 and expressed in Pichia pastoris. The 1,410-bp full-length gene encodes a polypeptide of 469 amino acids consisting of a putative signal peptide at residues 1-20, a catalytic domain of glycoside hydrolase family 7 (GH7), a short Thr/Ser-rich linker and a family 1 carbohydrate-binding module (CBM 1). The purified recombinant Cel7A had pH and temperature optima of pH 5.0 and 60°C, respectively, and showed broad pH adaptability (pH 3.0-6.0) and excellent stability at pH3.0-8.0 and 60°C. Belonging to the group of nonspecific endoglucanases, Cel7A exhibited the highest activity on barley β-glucan (2020 ± 9 U mg-1), moderate on lichenan and CMC-Na, and weak on laminarin, locust bean galactomannan, Avicel, and filter paper. Under simulated mashing conditions, addition of Cel7A (99 μg) reduced the mash viscosity by 9.1% and filtration time by 24.6%. These favorable enzymatic properties make Cel7A as a good candidate for applications in the brewing industry.Substantial changes in bone histology accompany the secondary adaptation to life in the water. This transition is well documented in several lineages of mammals and non-avian reptiles, but has received relatively little attention in birds. This study presents new observations on the long bone microstructure of penguins, based on histological sections from two extant taxa (Spheniscus and Aptenodytes) and eight fossil specimens belonging to stem lineages (†Palaeospheniscus and several indeterminate Eocene taxa). High bone density in penguins results from compaction of the internal cortical tissues, and thus penguin bones are best considered osteosclerotic rather than pachyostotic. Although the oldest specimens sampled in this study represent stages of penguin evolution that occurred at least 25 million years after the loss of flight, major differences in humeral structure were observed between these Eocene stem taxa and extant taxa. This indicates that the modification of flipper bone microstructure continued lxtant penguins, none was observed in any of the current sampled specimens. Therefore, it is likely that even these 'giant' penguin taxa completed their growth cycle without a major pause in bone deposition, implying that they did not undergo a prolonged fasting interval before reaching adult size.Abamectin is used in several countries as a type of macrocyclic lactone insecticide to control nematodes and other pests in livestock and agriculture. This medicine, used for animals and crops, would be highly toxic to human if a person has intentional poisoning. We report a case of a 47-year old man who was admitted to the hospital after ingestion of a large dose of abamectin on purpose, and who rapidly recovered consciousness after administration of flumazenil. Although flumazenil is not the antidote of abamectin, we may hypothesize that it could reduce recovery time and shorten expenditures in hospital. This is the first report that focusses on a specific treatment which could possibly accelerate recovery of consciousness for patients with abamectin intoxication.A case of a 45-year old woman with an ovarian dermoid cyst causing ureteric colic secondary to distal ureteral obstruction is reported. The dermoid cyst was observed on computed tomography to be adjacent to and compressing the distal left ureter and this was confirmed at surgical exploration. Following oophorectomy, the patient's symptoms completely resolved and the excised ovarian cyst was confirmed on pathological evaluation to be a dermoid cyst. This appears to be the first reported case of ureteral obstruction caused by an ovarian dermoid cyst in the English medical literature.Thermal shock is widely recognized by modern medicine. Its pathophysiological mechanisms are known, as are its possible consequences, but scientific reports in the literature about clinical cases with severe consequences are sparse. The authors present a case of cardiorespiratory arrest after prolonged sun exposure followed by a dive in the ocean. Other aetiological causes were ruled out, by exclusion, leading to the diagnosis of cardiorespiratory arrest caused by thermal shock. It is important to inform the public in general of the risks of negligent behaviour on the beach.External iliac arterial obstruction is relatively rare in renal transplantation, and may cause surgical failure and ipsilateral leg ischaemia. Prompt diagnosis and management of this kind of complication is essential to rescue the patient and allograft. Four patients with external iliac arterial obstruction caused by Satinsky atrauma forceps in renal transplantation were analysed and summarized. In case one, the obstruction of the external iliac artery distal to the renal allograft caused ipsilateral leg ischaemia. After surgical fixation of the endarterium, the patient recovered from the lower limb ischaemia. In case two, the obstruction of the external iliac artery was located proximal to the renal allograft. Since the endarterial rupture was not found and fixed in time, the renal allograft was lost. The third case was similar to the second. Based on the previous experience, we fixed the endarterium promptly and transplanted the kidney back successfully. In case four, there was endarterial rupture with atherosclerosis located around the anastomosis stoma. After taking out the atherosclerotic plaque and fixing the endarterium, the blood supply of kidney and lower limb was good. External iliac arterial rupture and obstruction caused by Satinsky atrauma forceps in renal transplantation is rare, but may cause severe and depressing outcome. The critical step is to find and fix the impaired endarterium as early as possible.

The past decade has seen an increasing focus on professionalism within the medical school curriculum. This reflects the growing demand for doctors who demonstrate empathy and uphold the altruistic values of the Hippocratic Oath. Such is often challenged by the resource-constrained environments of developing nations requiring uniquely tailored interventions within these regions.

As part of a wider effort to develop training of medical professionalism at our institution, an initiative was pursued to assess the current knowledge about and attitudes toward medical professionalism.

The study was designed as a cross-sectional descriptive study of fourth and fifth year medical students and junior doctors. A questionnaire was adapted and revised from a previously published study. Questions were grouped into categories pertaining to knowledge about professionalism and attitudes toward professionalism. Overall, 191 questionnaires were analysed (168 students and 23 doctors).

Junior doctors' scores were higher than medical students for all knowledge subscales but scores on the attitude subscales were significantly lower than medical students. Overall, in both groups, attitude scores were higher than knowledge scores. There was an overall trend of decreasing attitude scores as persons progressed through their training years and into clinical practice.

Results demonstrate limited knowledge about medical professionalism but good attitudes toward this trait. Taken together, this perhaps highlights a receptivity toward more formal training within this area that is also justified by the marked decline in attitude scores over time.

Results demonstrate limited knowledge about medical professionalism but good attitudes toward this trait. Taken together, this perhaps highlights a receptivity toward more formal training within this area that is also justified by the marked decline in attitude scores over time.Graft-versus-host disease (GVHD) is a lethal complication of allogeneic haematopoietic stem cell transplantation which limits its application. Psoralen was utilized in the treatment of GVHD as a second-line method, which is also known as extracorporeal photochemotherapy (ECP). In the process of ECP, mononuclear cells must be isolated from the body in advance then a photosensitizer, 8-methoxypsoralen (8-MOP, 200 μg/L for the final concentration), would be added to the cell suspension before its exposure to ultraviolet A [UVA; 365 nm, 2J/cm2]. The disposed lymphocytes re-infused into the body account for 5% to 15% of the lymphocytes in the body. The process of ECP is complicated, expensive and very labour intensive, which limits its popularity. We hypothesized that psoralen should be activated by ultraviolet A, and should be kept in activation for a relatively long time before it gets in contact with mononuclear cells. This kind of psoralen is called previously activated psoralen (PAP), which may have the same effects on GVHD as ECP, but would be much easier and economical to work with.

We reviewed the demographic pattern and distribution of deaths in the emergency department (ED) of the University College Hospital (UCH) in order to identify gaps in the standard of care, thereby providing evidence for intervention and enhanced research in acute care.

After obtaining institutional ethics approval, we retrospectively studied all deaths in the ED of UCH from January 1 to December 31, 2011. Data were retrieved from the ED's electronic register.

During the 12-month period, a total of 10 728 patients attended the emergency centre and 647 deaths occurred, giving a mortality rate of 6.0%. Male deaths constituted 62% of all deaths. The mean age at death was 44.5 ± 19.1 (range 5 months-92) years. The age group with the highest proportional mortality was 60-69 years (11.4%). Out of all deaths, 295 (45.6%) had alterations of consciousness. Medicine was the specialty with the most deaths (56%), followed by surgery (40%) and lastly, obstetrics and gynaecology (4%). Of the 190 patients that died from trauma, 153 (80.