Study of mitochondrial respiratory defects on reprogramming to human induced pluripotent stem cells

Reprogramming of somatic cells into a pluripotent state is known to be accompanied by extensive restructuring of mitochondria and switch in metabolic requirements. Here we utilized Leber''s hereditary optic neuropathy (LHON) as a mitochondrial disease model to study the effects of homoplasmic mtDNA mutations and subsequent oxidative phosphorylation (OXPHOS) defects in reprogramming. We obtained fibroblasts from a total of 6 LHON patients and control subjects, and showed a significant defect in complex I respiration in LHON fibroblasts by high-resolution respiratory analysis. Using episomal vector reprogramming, our results indicated that human induced pluripotent stem cell (hiPSC) generation is feasible in LHON fibroblasts. In particular, LHON-specific OXPHOS defects in fibroblasts only caused a mild reduction and did not significantly affect reprogramming efficiency, suggesting that hiPSC reprogramming can tolerate a certain degree of OXPHOS defects. Our results highlighted the induction of genes involved in mitochondrial biogenesis (TFAM, NRF1), mitochondrial fusion (MFN1, MFN2) and glycine production (GCAT) during reprogramming. However, LHON-associated OXPHOS defects did not alter the kinetics or expression levels of these genes during reprogramming. Together, our study provides new insights into the effects of mtDNA mutation and OXPHOS defects in reprogramming and genes associated with various aspects of mitochondrial biology.     

Wireless capsule endoscopy: Perspectives beyond gastrointestinal bleeding

Wireless capsule endoscopy (CE) is a technology developed for the endoscopic exploration of the small bowel. The first capsule model was approved by the Food and Drug Administration in 2001, and its first and essential indication was occult gastrointestinal (GI) bleeding. Over subsequent years, this technology has been refined to provide superior resolution, increased battery life, and capabilities to view different parts of the GI tract. Indeed, cases for which CE proved useful have increased significantly over the last few years, with new indications for the small bowel and technical improvements that have expanded its use to other parts of the GI tract, including the esophagus and colon. The main challenges in the development of CE are new devices with the ability to provide therapy, air inflation for a better vision of the small bowel, biopsy sampling systems attached to the capsule and the possibility to guide and move the capsule with an external motion control. In this article we review the current and new indications of CE, and the evolving technological changes shaping this technology, which has a promising potential in the coming future of gastroenterology.     

Emerging treatments for complex perianal fistula in Crohn＇s disease

Complex perianal fistulas have a negative impact on the quality of life of sufferers and should be treated. Correct diagnosis, characterization and classification of the fistulas are essential to optimize treatment. Nevertheless, in the case of patients whose fistulas are associated with Crohn＇s disease, complete closure is particularly difficult to achieve. Systemic medical treatments （antibiotics, thiopurines and other immunomodulatory agents, and, more recently, anti-tumor necrosis factor-α agents such as infliximab） have been tried with varying degrees of success. Combined medical （including infliximab） and less aggressive surgical therapy （drainage and seton placement） offer the best outcomes in complex Crohn＇s fistulas while more aggressive surgical procedures such as fistulotomy or fistulectomy may increase the risk of incontinence. This review will focus on emerging novel treatments for perianal disease in Crohn＇s patients. These include locally applied infliximab or tacrolimus, fistula plugs, instillation of fibrin glue and the use of adult expanded adipose-derived stem cell injection. More welldesigned controlled studies are required to confirm the effectiveness of these emerging treatments.     

急诊经尿道电切处理前列腺增生并发大出血尿潴留

该文报告５例前列腺增生症病人并发大出血潴留，经急诊内镜下清除膀胱内血块并电切增生的前列腺，获满意疗效。认为经尿道清血块并同时电切处理前列腺增生并大出血尿潴留，具有创伤小，疗效确切，费用省之优点，但病人一般情况差和术者ＴＵＲＰ经验不足时，清除血块解除尿潴留和切除前列腺应分期进行，不然容易发生并发症。     

CLINICAL AND EPIDEMIOLOGICAL PROFILE OF ELDERLY PATIENTS WITH CHAGAS DISEASE FOLLOWED BETWEEN 2005-2013 BY PHARMACEUTICAL CARE SERVICE IN CEARá STATE, NORTHEASTERN BRAZIL

By controlling the transmission of Chagas disease, the challenge of providingassistance to millions of infected patients that reach old age arises. In this study,the socioeconomic, demographic and comorbidity records of all elderly chagasicpatients followed at the Pharmaceutical Care Service of the Chagas Disease ResearchLaboratory were assessed. The information related to the clinical form of the diseasewas obtained from medical records provided by the Walter Cantídio UniversityHospital. The profile of the studied population was: women (50.5%); mean age of 67years; retired (54.6%); married (51.6 %); high illiteracy rate (40.2%); and familyincome equal to the minimum wage (51.5%). The predominant clinical forms of Chagasdisease were cardiac (65.3%) and indeterminate (14.7%). The main electrocardiographicchanges were the right bundle branch block (41.0%), associated or not with theanterosuperior left bundle branch block (27.4%). The average number of comorbiditiesper patient was 2.23 ± 1.54, with systemic arterial hypertension being the main onefound (67.0%). It was found that the elderly comprise a vulnerable group of patientsthat associate aging with cardiac and/or digestive disorders resulting from theevolution of Chagas disease and other comorbidities, which requires special attentionfrom health services to ensure more appropriate medical and social care.     

Effect of eugenol-based endodontic cement on the adhesion of intraradicular posts

The present study evaluated, in vitro, the influence of an eugenol-based endodontic sealer (EndoFill) on the adhesion of intra-radicular posts cemented with a resin-based cement (Enforce) ou a zinc phosphate cement. Twenty-four single-rooted maxillary canines were divided into 2 groups (n=12) and obturated with either gutta-percha points plus EndoFill or gutta-percha points alone (no cement). In each group, half of intracanal posts (n=6) were cemented with Enforce resin-based cement and half with zinc phosphate cement. Specimens were submitted to pull-out test in an Instron machine and tensile force was applied at a crosshead speed of 0.5 mm/min until post dislodgement. The maximum forces required for post removal was recorded (N) and means were submitted to statistical analysis by Kruskal-Wallis test (p<0.01). Posts cemented with zinc phosphate cement were significantly more retentive (353.4 N) than those cemented with Enforce (134.9 N) (p<0.01). Regarding the influence of the eugenol-based cement (EndoFill) on post retention, there was statistically significant difference (p<0.01) only between the groups cemented with Enforce, i.e., in the canals filled with EndoFill + guta-percha there was lower bond strength than in the canals filled with gutta-percha points alone (101.5 and 168.2 N, respectively). In conclusion, the zinc-phosphate-based cement showed greater post retention than the resin-based cement. The findings of this study suggest that the eugenol-containing sealer interfered with the adhesive properties of the resin-based cement.     

Climate,vocal folds,and tonal languages: Connecting the physiological and geographic dots

We summarize a number of findings in laryngology demonstrating that perturbations of phonation, including increased jitter and shimmer, are associated with desiccated ambient air. We predict that, given the relative imprecision of vocal fold vibration in desiccated versus humid contexts, arid and cold ecologies should be less amenable, when contrasted to warm and humid ecologies, to the development of languages with phonemic tone, especially complex tone. This prediction is supported by data from two large independently coded databases representing 3,700+ languages. Languages with complex tonality have generally not developed in very cold or otherwise desiccated climates, in accordance with the physiologically based predictions. The predicted global geographic–linguistic association is shown to operate within continents, within major language families, and across language isolates. Our results offer evidence that human sound systems are influenced by environmental factors.A standard assumption in linguistics is that sound systems are immune to ecological effects (1). This presumption has been called into question by several recent studies providing evidence for a correlation between aspects of phonology (such as sonority) and climatic and geographic factors (such as temperature, plant cover, or terrain), as well as behaviors associated with such factors (2–9). Most recently, a correlation was uncovered between ejective sounds and regions of high elevation in a sample of nearly 600 languages (10). Although two plausible physiological motivations are offered in ref. 10 for the correlation between ejective use and reduced ambient air pressure, those explanations have yet to be supported by experimental evidence. The uncovered patterns could be epiphenomenal, and in general, the cross-linguistic statistical studies in question have not been buttressed by experimental support (11).In this study, we offer evidence for a negative correlation between linguistic tone and characteristic rates of desiccation in ambient air. In contradistinction to the aforementioned studies offering geographic/phonetic correlations, however, we suggest this correlation is predicted by extensive experimental research on the properties of the human larynx. This research, which has been conducted by numerous laryngologists over the last decade and a half, has not been previously tied to the distribution of the world’s tonal languages. We submit that the research predicts that the relatively precise manipulation of the vocal folds associated with tone, especially complex tone, should be more difficult to achieve in arid climates—particularly very cold ones—when contrasted to warmer and more humid climates. We offer global, continental, and intralinguistic-family data consistent with the expected geographic/tonemic association. Our results cannot facilely be ascribed to well-known phylogenetic and areal relatedness. We conclude by suggesting that the most reasonable interpretation of the data is that the articulation of linguistic sounds is ecologically adaptive, just like other forms of human behavior.     

Documento de consenso sobre codificação de exames de ressonância magnética cardíaca em Portugal

One of the obstacles to more frequent and appropriate use of cardiac magnetic resonance (CMR) in Portugal has been the lack of specific codes that accurately describe these examinations as they are currently performed. In this consensus document, recommendations are made for updating and standardizing CMR codes in Portugal. Guidance on which techniques and codes should be used in the most common clinical scenarios is also provided.