Effect of ulcer healing on the prognosis of chronic gastric uler. Four-year follow-up

Eighty three patients were followed-up for four years after an admission to hospital with a chronic gastric ulcer proven by radiology (index ulcer). The index ulcer healed completely in 50 patients, but was unhealed at the time of discharge in the other 33. Significantly fewer patients whose index ulcer was healed compared with those whose ulcer was unhealed at discharge had had a recurrence by one (p < 0.05), two, three and four years' (p < 0.01) follow-up. Moreover, the rate of recurrence was significantly greater for those patients with unhealed, compared with those with a healed index ulcer (p < 0.05) and by the end of the four-year period 61% of patients with unhealed, compared with 26% of those with healed index ulcers had had a recurrence. Patients over the age of 60 years with unhealed index ulcers had a significantly poorer prognosis than those of similar age whose index ulcer was healed at discharge (p < 0.025). The sex of the ulcer patient did not significantly influence ulcer recurrence. Large ulcers (> 57 mm(2)) were less often healed on initial discharge and were more frequently associated with recurrence at one (p < 0.05), two (p < 0.025), three and four years (p < 0.01) than smaller ulcers ([unk]57 mm(2)). Heavy intake of analgesics adversely influenced the course of patients whose ulcer was unhealed (p < 0.05), but did not alter the recurrence rate in those whose ulcer was healed. Ulcer recurrence was not influenced by smoking habits or by alcohol consumption.     

Derivation of na?ve human embryonic stem cells

The naïve pluripotent state has been shown in mice to lead to broad and more robust developmental potential relative to primed mouse epiblast cells. The human naïve ES cell state has eluded derivation without the use of transgenes, and forced expression of OCT4, KLF4, and KLF2 allows maintenance of human cells in a naïve state [Hanna J, et al. (2010) Proc Natl Acad Sci USA 107(20):9222–9227]. We describe two routes to generate nontransgenic naïve human ES cells (hESCs). The first is by reverse toggling of preexisting primed hESC lines by preculture in the histone deacetylase inhibitors butyrate and suberoylanilide hydroxamic acid, followed by culture in MEK/ERK and GSK3 inhibitors (2i) with FGF2. The second route is by direct derivation from a human embryo in 2i with FGF2. We show that human naïve cells meet mouse criteria for the naïve state by growth characteristics, antibody labeling profile, gene expression, X-inactivation profile, mitochondrial morphology, microRNA profile and development in the context of teratomas. hESCs can exist in a naïve state without the need for transgenes. Direct derivation is an elusive, but attainable, process, leading to cells at the earliest stage of in vitro pluripotency described for humans. Reverse toggling of primed cells to naïve is efficient and reproducible.It has become clear with the derivation of mouse epiblast stem cells (mEpiSCs) that pluripotency encompasses more than one stage of development (1, 2). The earlier “naïve” stage represents the preimplantation inner cell mass, typified by mouse ES cells (mESCs), and the “primed,” the postimplantation epiblast, typified by mEpiSCs and human ES cells (hESCs). The challenge in naïve cell maintenance has been protecting cells from differentiation stimuli. This has been achieved in mESCs through exposure to leukemia inhibitory factor (LIF), whereas addition of extracellular signal-regulated kinase (MEK) and glycogen synthase kinase 3 (GSK3) inhibitors (2i) in defined medium allows the cells to attain a homogeneous ground state (3). Defining characteristics of the naïve/ground vs. primed states are shown in Fig. S1A. In humans, the naïve stage has been difficult to capture as a stable in vitro state.There are practical advantages that come with a human naïve state. Among them is ease of trypsin passage and developmental capacity. Whole animals can be generated from good naïve mESCs through tetraploid complementation (4), and mEpiSCs cannot contribute to chimerism. Being more comparable to mESCs, naïve hESCs will likely allow increased developmental potential and a more accurate correlation to mESC data.It has been reported that human induced pluripotent cells (h-iPSCs) can be maintained in the naïve state if the pluripotency-inducing transgenes are not silenced (5). Only recently have hESCs been maintained in a naïve state without transgenes (6). Our primary aim was to generate naïve hESCs not dependent upon transgenes for stable culture. We toggled existing human ESC and mouse mEpiSC lines back from the primed state to grow under the influence of 2i without the need for Activin A. This helped us to define appropriate culture conditions for human naïve cells and allowed the de novo derivation of a naïve hESC line, Elf1. We report on the naïve state of human ESCs capable of unlimited culture in 2i.     

Determinants of cardiomyocyte development in long-term primary culture

The influence of cell attachment to substrates and of medium composition on development of cardiomyocytes from adult rats in cultures up to 9 days old was investigated. Cardiomyocytes prevented from attaching to a culture substratum deteriorated within 3 days in medium 199 (M199) with or without fetal calf serum (FCS). Rapid attachment during the first 4 h after plating could be attained equally well on FCS or laminin coated surfaces. In M199 without FCS, attached cardiomyocytes on FCS coated dishes were able to retain their overall elongated morphology, but the number of cells remaining attached constantly decreased during the first 9 days in serum free culture. Attached on laminin the rate of loss from serum free cultures was lower. In the presence of 20% FCS, attached cardiomyocytes spread extensively after day 3, both on FCS and on laminin coated dishes. In serum containing media many cells pass through a spherical intermediate state before spreading extensively. Almost all cardiomyocytes cultured with 20% FCS on untreated tissue culture plastic gradually become spherical before attaching. With 20% FCS in culture media, the number of cells remaining in culture after 9 days was similar whether cells were rapidly attached to FCS treated or laminin coated substrata, or were plated on culture plastic, i.e., 52, 63, and 45% of the maximal number attached on day 1. By day 9 in all three culture types cells were spread and were beating spontaneously. These results indicate that adult cardiomyocytes do not establish in a stable morphological state in long-term cultures, in other than a surface attached spread cell form. For this stability the presence of yet unidentified components of fetal calf serum is required.     

Medical student perceptions of research and research-orientated careers: An international questionnaire study

Background: Engaging and inspiring the next generation of physician-scientists at an early stage is recognised as key to ensure the future of medical research. However, little is known about medical student perceptions of research.

Objectives: We attempted to ascertain perceptions of research and research-orientated careers from medical students studying in different countries.

Methods: An online questionnaire was developed, piloted, and promoted to medical students in various countries.

Results: 1625 responses were collected from 38 countries. Analysis was restricted to data collected from countries with >100 responses (n?=?890). Less than half the respondents felt their medical school provided adequate research training. Key perceived barriers to research participation as a student included lack of time and difficulty finding mentors or projects. A significant gender disparity existed in research ambitions of students with females desiring less research involvement. The importance of barriers and satisfaction with research training differed significantly between countries.

Conclusions: Students perceive a number of key barriers to research involvement and pursuit of research-orientated careers. Programmes designed to engage students with research should focus on overcoming identified barriers. Greater effort is needed to engage female students who report more significant barriers and less desire to follow research-orientated careers.     

Cellular mechanisms of ischemia-reperfusion injury

As of yet, only a few strategies to prevent myocardial reperfusion injury have been tested clinically. In the first minutes of reperfusion, the myocardium can be damaged by contracture development, causing mechanical stiffness, tissue necrosis, and the "stone heart" phenomenon. Reperfusion-induced contracture can have two different causes, namely, Ca2+overload-induced contracture or rigor-type contracture. Ca2+ contracture results from rapid re-energization of contractile cells with a persistent Ca2+ overload. Strategies to prevent this type of injury are directed at cytosolic Ca2+ control or myofibrillar Ca2+ sensitivity. Rigor-contracture occurs when re-energization proceeds very slowly. It does not depend on Ca2+ overload. It may be prevented by strategies improving early mitochondrial reactivation     

Species of Propionibacterium and Propionibacterium acnes phylotypes associated with orthopedic implants

Propionibacterium sp. is commonly isolated in association with orthopedic implants, either as a pathogen or a colonizer. Microbial characteristics that indicate whether the isolated species is a likely cause of orthopedic implant infection versus a colonizing agent would be clinically useful. We performed a prospective trial to determine the species of Propionibacterium and the phylotype (IA, IB, II, III) of Propionibacterium acnes isolated from the surface of removed orthopedic implants, and we correlated these findings with the presence or absence of infection. P. acnes represented 61 of 62 isolates. P. acnes type I was more commonly isolated than was type II (62% versus 38%, respectively), whether associated with infection or not. P. acnes type III was not detected. There was no clear association between types I and II P. acnes and infection or colonization of failed orthopedic implants (P = 0.75), however type IB strains were more frequently isolated than type IA from infected prosthese.     

关注健康,没有借口——高寿糖尿病明星Louis Zorich的健康态度

<正>"不管存在多少借口,预防和控制糖尿病比出现并发症后再去补救要容易得多。"2008年11月的一次常规体检后,84岁高龄的美国著名演员Louis Zorich得知自己患上了糖尿病。