The role of diet and exercise in type 2 diabetes prevention

Although traditionally seen in middle aged and older people Type 2 diabetes, which is associated with obesity, poor diet and lack of exercise, is increasingly being diagnosed in children and young people who are overweight. Studies from around the world point to the usefulness of diet and exercise regimens in preventing onset of this illness.     

A systematic review of electrical stimulation for pressure ulcer prevention and treatment in people with spinal cord injuries

Context

Electrical stimulation (ES) can confer benefit to pressure ulcer (PU) prevention and treatment in spinal cord injuries (SCIs). However, clinical guidelines regarding the use of ES for PU management in SCI remain limited.

Objectives

To critically appraise and synthesize the research evidence on ES for PU prevention and treatment in SCI.

Method

Review was limited to peer-reviewed studies published in English from 1970 to July 2013. Studies included randomized controlled trials (RCTs), non-RCTs, prospective cohort studies, case series, case control, and case report studies. Target population included adults with SCI. Interventions of any type of ES were accepted. Any outcome measuring effectiveness of PU prevention and treatment was included. Methodological quality was evaluated using established instruments.

Results

Twenty-seven studies were included, 9 of 27 studies were RCTs. Six RCTs were therapeutic trials. ES enhanced PU healing in all 11 therapeutic studies. Two types of ES modalities were identified in therapeutic studies (surface electrodes, anal probe), four types of modalities in preventive studies (surface electrodes, ES shorts, sacral anterior nerve root implant, neuromuscular ES implant).

Conclusion

The methodological quality of the studies was poor, in particular for prevention studies. A significant effect of ES on enhancement of PU healing is shown in limited Grade I evidence. The great variability in ES parameters, stimulating locations, and outcome measure leads to an inability to advocate any one standard approach for PU therapy or prevention. Future research is suggested to improve the design of ES devices, standardize ES parameters, and conduct more rigorous trials.     

An age-related ovarian phenotype in mice with targeted disruption of the Cyp 19 (aromatase) gene

With the development of a mouse model of estrogen insufficiency due to targeted disruption of the aromatase gene [the aromatase knockout (ArKO) mouse], a new opportunity exists to examine the role of estrogen in ovarian follicular development. Ovaries and serum were collected from wild-type, heterozygous, and ArKO mice at 10-12 and 21-23 weeks and 1 yr of age. The ovaries were assessed histologically and stereologically, with primary, secondary, and antral follicles and corpora lutea counted. The uteri were hypoestrogenic, and serum levels of LH and FSH in ArKO females were elevated above those in heterozygote and wild-type animals at all ages studied. Although estrogen was not a prerequisite for reinitiation of follicle growth, there was a block of follicular development, and no corpora lutea were present in ArKO ovaries. Thus, the ArKO mouse was infertile as a consequence of disrupted folliculogenesis and a failure to ovulate. Hemorrhagic cystic follicles were present by 21-23 weeks of age. The ovarian phenotype degenerated with age, such that by 1 yr there were no secondary or antral follicles, and the primary follicles present were atretic. Extensive interstitial tissue remodeling occurred, exemplified by an influx of macrophages and collagen deposition, coincident with the loss of follicles. In conclusion, the ovarian environment in ArKO mice does not allow the characteristic development of follicles that culminates in ovulation and demonstrates an in vivo requirement of estrogen for normal ovarian function in the mouse.     

巨噬细胞迁移抑制因子通过CC趋化因子配体2诱导巨噬细胞聚集

巨噬细胞迁移抑制因子最初是由于能抑制体外巨噬细胞随机迁移而被发现,现在它作为一种重要的调节因子参与一系列炎症性疾病过程.我们最近发现,巨噬细胞迁移抑制因子的缺失使一些由炎症介质诱发的白细胞-内皮细胞相互作用减弱,提示巨噬细胞迁移抑制因子在炎症反应中起作用的机制之一是促进白细胞聚集.……     

Syngeneic transplantation with peripheral blood mononuclear cells collected after the administration of recombinant human granulocyte colony-stimulating factor

Five syngeneic transplants were performed in four patients following myeloablative therapy using unmodified peripheral blood mononuclear cells (PBMCs) collected after the administration of recombinant human granulocyte colony stimulating factor (rhG-CSF) to normal donors. The only toxicity experienced by the four normal donors was bone pain. Four patients received two collections of PBMCs, and a second transplant was performed in one patient with one collection. The patients received a median of 20.53 x 10(8) total nucleated cells/kg (range 20 to 25.5), 11.3 x 10(8) total mononuclear cells/kg (range 6.52 to 17.2), 113.1 x 10(4)/kg CFU-GM (range 46.7 to 211.8) and 9.6 x 10(6) CD34+ cells/kg (range 1.6 to 12.6) Post-transplant growth factors were not administered. The median time to an absolute neutrophil count greater than 0.5 x 10(9)/L was 14 days (range 10 to 18). The median time to platelet transfusion independence was 11 days (range 10 to 13). Two patients had the number of CD3+ T lymphocytes determined in the pheresis product. An average of 3.04 x 10(10) CD3+ cells were collected per pheresis. This represents an approximate 1 log increase over the number of T lymphocytes in a typical bone marrow transplant. Rh-GCSF can be used to mobilize peripheral blood progenitor cells from normal donors with minimal toxicity. Studies of allogeneic transplants using PBMCs collected after rhG-CSF administration to determine permanent grafting ability and the incidence and severity of graft-versus-host disease are warranted.     

Cooperation between the activin and Wnt pathways in the spatial control of organizer gene expression

The normal expression pattern of the Wnt responsive homeobox gene Siamois is restricted to the dorso-vegetal region of the Xenopus embryo. Because the Wnt signaling pathway (via β-catenin) is active on the entire dorsal side of the early embryo, we have asked why Siamois expression is not seen in the dorsal ectoderm. Only Wnt signaling, via activation of β-catenin, can induce directly Siamois, and signaling via the SMAD1 (BMP2/4) or SMAD2 (activin/Vg-1) pathways cannot. We now directly show that the SMAD2 pathway can cooperate with the Wnt pathway to induce expression of Siamois much more strongly than the Wnt pathway alone, in normal embryos. We demonstrate the significance of this cooperation in normal embryos by blocking the SMAD2 signaling pathway with a dominant negative activin receptor. The activin dominant negative receptor blocks this cooperative effect and reduces the expression of Siamois by threefold in early embryos. Furthermore, we find that this cooperative relationship between the SMAD2 and Wnt pathways is reciprocal. Thus, in normal embryos, the Wnt pathway can enhance induction, by the SMAD 2 pathway, of the organizer genes Gsc and Chd but not the pan-mesodermal marker genes Xbra and Eomes. We conclude that the Wnt and SMAD2 signaling pathways cooperate to induce the expression of Spemann-organizer specific genes and so help to localize their spatial expression.     

Retrovirally marked CD34-enriched peripheral blood and bone marrow cells contribute to long-term engraftment after autologous transplantation

We report here on a preliminary human autologous transplantation study of retroviral gene transfer to bone marrow (BM) and peripheral blood (PB)-derived CD34-enriched cells. Eleven patients with multiple myeloma or breast cancer had cyclophosphamide and filgrastim-mobilized PB cells CD34-enriched and transduced with a retroviral marking vector containing the neomycin resistance gene, and CD34-enriched BM cells transduced with a second marking vector also containing a neomycin resistance gene. After high-dose conditioning therapy, both transduced cell populations were reinfused and patients were followed over time for the presence of the marker gene and any adverse effects related to the gene-transfer procedure. All 10 evaluable patients had the marker gene detected at the time of engraftment, and 3 of 9 patients had persistence of the marker gene for greater than 18 months posttransplantation. The marker gene was detected in multiple lineages, including granulocytes, T cells, and B cells. The source of the marking was both the transduced PB graft and the BM graft, with a suggestion of better long-term marking originating from the PB graft. The steady- state levels of marking were low, with only 1:1000 to 1:10,000 cells positive. There was no toxicity noted, and patients did not develop detectable replication-competent helper virus at any time posttransplantation. These results suggest that mobilized PB cells may be preferable to BM for gene therapy applications and that progeny of mobilized peripheral blood cells can contribute long-term to engraftment of multiple lineages.