Hydrogen sulfide bypasses the rate-limiting oxygen activation of heme oxygenase.

Discovery of unidentified protein functions is of biological importance because it often provides new paradigms for many research areas. Mammalian heme oxygenase (HO) enzyme catalyzes the O2-dependent degradation of heme into carbon monoxide (CO), iron, and biliverdin through numerous reaction intermediates. Here, we report that H2S, a gaseous signaling molecule, is part of a novel reaction pathway that drastically alters HO's products, reaction mechanism, and catalytic properties. Our prediction of this interplay is based on the unique reactivity of H2S with one of the HO intermediates. We found that in the presence of H2S, HO produces new linear tetrapyrroles, which we identified as isomers of sulfur-containing biliverdin (SBV), and that only H2S, but not GSH, cysteine, and polysulfides, induces SBV formation. As BV is converted to bilirubin (BR), SBV is enzymatically reduced to sulfur-containing bilirubin (SBR), which shares similar properties such as antioxidative effects with normal BR. SBR was detected in culture media of mouse macrophages, confirming the existence of this H2S-induced reaction in mammalian cells. H2S reacted specifically with a ferric verdoheme intermediate of HO, and verdoheme cleavage proceeded through an O2-independent hydrolysis-like mechanism. This change in activation mode diminished O2 dependence of the overall HO activity, circumventing the rate-limiting O2 activation of HO. We propose that H2S could largely affect O2 sensing by mammalian HO, which is supposed to relay hypoxic signals by decreasing CO output to regulate cellular functions. Moreover, the novel H2S-induced reaction identified here helps sustain HO's heme-degrading and antioxidant-generating capacity under highly hypoxic conditions.

A presumptive case of Baylisascaris procyonis in a feral green-cheeked Amazon parrot (Amazona viridigenalis).

A feral green-cheeked Amazon parrot (Amazona viridigenalis), also known as the red-crowned Amazon, with generalized neurologic symptoms was found in Pasadena in Southern California and brought in for treatment. The bird was refractory to a wide variety of medications and supportive treatment. Tests for polyoma virus, psittacine beak and feather disease virus, and West Nile virus as well as Chlamydophila psittaci were negative. Hospitalized and home care continued for a total of 69 days. The bird was rehospitalized on day 66 for increasing severity of clinical signs and found 3 days later hanging with its head down, in respiratory arrest. Resuscitation was unsuccessful. There were no gross pathologic lesions. Histopathology showed a focal subcutaneous fungal caseous granuloma under the skin of the dorsum. Many sarcocysts morphologically consistent with Sarcocystis falcatula were found in the cytoplasm of the skeletal myofibers from skeletal muscles of different locations of this bird, a finding that was considered an incidental, clinically nonsignificant finding in this case. Necrosis with microscopic lesions typical of Baylisascaris spp. neural larva migrans was in the brain. Although multiple histologic serial sections of the brain were examined and a brain squash performed and analyzed, no Baylisascaris larvae were found. This is the first presumptive case of Baylisascaris in a feral psittacine.

Development and Effectiveness of an End-of-Life Care Program for Faculty in the Critical Care Field: A Randomized Controlled Trial.

In Japan, end-of-life care education in the critical care field is still insufficient. Therefore, this study developed and verified the effectiveness of an end-of-life care program for faculty in the critical care field in Japan through a randomized controlled trial. The study was implemented from September 2016 to March 2017. Participants were 82 college teaching staff and nurses working in the critical care field. Six months after the program, data of 37 members (84.1%) of the intervention and 39 members (88.6%) of the control group were analyzed. The results demonstrated that the primary end point-"confidence in teaching" 6 months after program completion-differed significantly between the 2 groups (2.5 [0.69] in the intervention group vs 1.8 [0.46] in the control group, P < .001). It is suggested that attending this program will give faculty in the field of critical care continued confidence in their end-of-life care teaching, as well as allow them to implement end-of-life care teaching in their field.

Conservative treatment of an aortoesophagial fistula after endovascular stent grafting for a thoracic aortic aneurysm.

BACKGROUND: Aortoesophageal fistula (AEF) is an uncommon condition that presents a problem in therapy because of the high rate of morbidity and mortality associated with its surgical management and the uniformly fatal outcome of medical treatment. In this article we describe a case of secondary AEF after endoluminal stent grafting of the thoracic aorta, which was observed by only conservative management and followed up for 14 months with no signs of recurrent hemorrhage or chronic mediastinitis. CASE REPORT: A 54-year old man with hepatocellular carcinoma (HCC) was admitted to our hospital because of tarry stool. He had a history of traumatic aneurysm, and undergone segmental replacement with a stent graft three years ago. After admission, Esophagogastroduodenoscopy and computed tomography identified AEF. He was treated conservatively, because his stage of HCC was advanced. Oral intake was prohibited, and the patient received proton pump inhibitors, intravenous hyperalimentation and antibiotics. Afterwards, no signs of hemorrhage were observed. Although oral intake was resumed after that, another bleeding event or development of mediastinitis was not observed. Subsequently, He was received chemotherapy for advanced HCC, and we observed downstaging of his advanced HCC. CONCLUSIONS: Although we observed 14 months survival in our case under conservative management of secondary AEF, it seems that the treatment of secondary AEF should do the operative management.

Survey of actual conditions of reasons for nurse calls: comparing a surgical ward and a medical ward.

We believe that nurse calls can play a role not merely as a means to convey patients' needs, but also as a medium to analyze and predict patients' needs using historical data of nurse calls. Therefore, we conducted a survey of actual conditions of nurse calls using "call history management system" developed for welfare institutions. The survey was intended to show patients' needs accurately by individually associating historical data, which can be collected through an information system, with reasons for calling, which usually cannot be collected automatically. Total quantities of nurse calls were 5,397 (174.1 per day, 4.59 per day per person) in the Surgery Ward and 3,404 (109.8 per day, 2.85 per day per person) in the Internal Medicine Ward; the incoming calls to the Surgical Ward were more numerous than those to the Medical Ward. The most common reason for calling was "assistance related to toileting". During the day shift and evening shift, that reason was followed by "fluid management" such as finishing of fluid administration and fluid exchange.

Effect of collagenase concentration on the isolation of small adipocytes from human buccal fat pad.

Dedifferentiated fat (DFAT) cells were isolated from mature adipocytes using the ceiling culture method. Recently, we successfully isolated DFAT cells from adipocytes with a relatively small size (<40 µm). DFAT cells have a higher osteogenic potential than that of medium adipocytes. Therefore, the objective of this study was to determine the optimal concentration of collagenase solution for isolating small adipocytes from human buccal fat pads (BFPs). Four concentrations of collagenase solution (0.01%, 0.02%, 0.1%, and 0.5%) were used, and their effectiveness was assessed by the number of small adipocytes and DFAT cells isolated. The total number of floating adipocytes that dissociated with 0.02% collagenase was 2.5 times of that dissociated with 0.1% collagenase. The number of floating adipocytes with a diameter of ≤29 µm that dissociated with 0.02% collagenase was thrice of those dissociated with 0.1% and 0.5% collagenase. The number of DFAT cells that dissociated with 0.02% collagenase was 1.5 times of that dissociated with 0.1% collagenase. In addition, DFAT cells that dissociated with 0.02% collagenase had a higher osteogenic differentiation potential than those that dissociated with 0.1% collagenase. These results suggest that 0.02% is the optimal collagenase concentration for isolating small adipocytes from BFPs.

Small Buccal Fat Pad Cells Have High Osteogenic Differentiation Potential.

Dedifferentiated fat (DFAT) cells derived from mature adipocytes have mesenchymal stem cells' (MSCs) characteristics. Generally, mature adipocytes are 60-110 µm in diameter; however, association between adipocyte size and dedifferentiation efficiency is still unknown. This study, therefore, investigated the dedifferentiation efficiency of adipocytes based on cell diameter. Buccal fat pad was harvested from five human donors and dissociated by collagenase digestion. After exclusion of unwanted stromal cells by centrifugation, floating adipocytes were collected and their size distribution was analyzed. The floating adipocytes were then separated into two groups depending on cell size using 40- and 100-µm nylon mesh filters: cell diameters less than 40 µm (small adipocytes: S-adipocytes) and cell diameters of 40-100 µm (large adipocytes: L-adipocytes). Finally, we evaluated the efficiency of adipocyte dedifferentiation and then characterized the resultant DFAT cells. The S-adipocytes showed a higher capacity to dedifferentiate into DFAT cells (S-DFAT cells) compared to the L-adipocytes (L-DFAT cells). The S-DFAT cells also showed a relatively higher proportion of CD146-positive cells than L-DFAT cells, and exhibited more osteogenic differentiation ability based on the alkaline phosphatase activity and amount of calcium deposition. These results suggested that the S- and L-DFAT cells had distinct characteristics, and that the higher dedifferentiation potential of S-adipocytes compared to L-adipocytes gives the former group an advantage in yielding DFAT cells.

Use of Rat Mature Adipocyte-Derived Dedifferentiated Fat Cells as a Cell Source for Periodontal Tissue Regeneration.

Lipid-free fibroblast-like cells, known as dedifferentiated fat (DFAT) cells, can be generated from mature adipocytes with a large single lipid droplet. DFAT cells can re-establish their active proliferation ability and can transdifferentiate into various cell types under appropriate culture conditions. The first objective of this study was to compare the multilineage differentiation potential of DFAT cells with that of adipose-derived stem cells (ASCs) on mesenchymal stem cells. We obtained DFAT cells and ASCs from inbred rats and found that rat DFAT cells possess higher osteogenic differentiation potential than rat ASCs. On the other hand, DFAT cells show similar adipogenic differentiation, and chondrogenic differentiation potential in comparison with ASCs. The second objective of this study was to assess the regenerative potential of DFAT cells combined with novel solid scaffolds composed of PLGA (Poly d, l-lactic-co-glycolic acid) on periodontal tissue, and to compare this with the regenerative potential of ASCs combined with PLGA scaffolds. Cultured DFAT cells and ASCs were seeded onto PLGA scaffolds (DFAT/PLGA and ASCs/PLGA) and transplanted into periodontal fenestration defects in rat mandible. Micro computed tomography analysis revealed a significantly higher amount of bone regeneration in the DFAT/PLGA group compared with that of ASCs/PLGA and PLGA-alone groups at 2, 3, and 5 weeks after transplantation. Similarly, histomorphometric analysis showed that DFAT/PLGA groups had significantly greater width of cementum, periodontal ligament and alveolar bone than ASCs/PLGA and PLGA-alone groups. In addition, transplanted fluorescent-labeled DFAT cells were observed in the periodontal ligament beside the newly formed bone and cementum. These findings suggest that DFAT cells have a greater potential for enhancing periodontal tissue regeneration than ASCs. Therefore, DFAT cells are a promising cell source for periodontium regeneration.

The effectiveness of an interactive 3-dimensional computer graphics model for medical education.

BACKGROUND: Medical students often have difficulty achieving a conceptual understanding of 3-dimensional (3D) anatomy, such as bone alignment, muscles, and complex movements, from 2-dimensional (2D) images. To this end, animated and interactive 3-dimensional computer graphics (3DCG) can provide better visual information to users. In medical fields, research on the advantages of 3DCG in medical education is relatively new. OBJECTIVE: To determine the educational effectiveness of interactive 3DCG. METHODS: We divided 100 participants (27 men, mean (SD) age 17.9 (0.6) years, and 73 women, mean (SD) age 18.1 (1.1) years) from the Health Sciences University of Mongolia (HSUM) into 3DCG (n = 50) and textbook-only (control) (n = 50) groups. The control group used a textbook and 2D images, while the 3DCG group was trained to use the interactive 3DCG shoulder model in addition to a textbook. We conducted a questionnaire survey via an encrypted satellite network between HSUM and Tokushima University. The questionnaire was scored on a 5-point Likert scale from strongly disagree (score 1) to strongly agree (score 5). RESULTS: Interactive 3DCG was effective in undergraduate medical education. Specifically, there was a significant difference in mean (SD) scores between the 3DCG and control groups in their response to questionnaire items regarding content (4.26 (0.69) vs 3.85 (0.68), P = .001) and teaching methods (4.33 (0.65) vs 3.74 (0.79), P < .001), but no significant difference in the Web category. Participants also provided meaningful comments on the advantages of interactive 3DCG. CONCLUSIONS: Interactive 3DCG materials have positive effects on medical education when properly integrated into conventional education. In particular, our results suggest that interactive 3DCG is more efficient than textbooks alone in medical education and can motivate students to understand complex anatomical structures.

Current Approach to Rodents as Patients.

Rodent species are routinely presented to veterinary hospitals for wellness checks and different illnesses. When rodents are presented to the veterinarian for diagnosis and treatment, they deserve the same thorough approach that any other domestic species receives. The purpose of this article is to provide readers a review of the current information regarding examination, diagnosis, and treatment of some of the most common conditions for which rodent patients are presented. This article will cover 5 of the most common rodent species presented to veterinarians: guinea pigs, chinchillas, rats, mice, and hamsters.