Optimal insulin regimens in type 2 diabetes mellitus: systematic review and meta-analyses

Aims/hypothesis  

We compared the effect of biphasic, basal or prandial insulin regimens on glucose control, clinical outcomes and adverse events in people with type 2 diabetes.     

Studies on isolated gut mucosal lymphocytes in inflammatory bowel disease

Digestive Diseases and Sciences - To determine whether a defective proliferation of gut mucosal lymphocytes is a contributory factor to the pathogenesis of inflammatory bowel disease, we assessed...     

The CD11b promoter directs high-level expression of reporter genes in macrophages in transgenic mice [published erratum appears in Blood 1995 Apr 1;85(7):1983]

CD11b is the alpha chain of the Mac-1 integrin and is preferentially expressed in myeloid cells (neutrophils, monocytes, and macrophages). We have previously shown that the CD11b promoter directs cell-type- specific expression in myeloid lines using transient transfection assays. To confirm that these promoter sequences contain the proper regulatory elements for correct myeloid expression of CD11b in vivo, we have used the -1.7-kb human CD11b promoter to direct reporter gene expression in transgenic mice. Stable founder lines were generated with two different reporter genes, a Thy 1.1 surface marker and the Escherichia coli lacZ (beta-galactosidase) gene. Analysis of founders generated with each reporter demonstrated that the CD11b promoter was capable of driving high levels of transgene expression in murine macrophages for the lifetime of the animals. Similar to the endogenous gene, transgene expression was preferentially found in mature monocytes, macrophages, and neutrophils and not in myeloid precursors. These experiments indicate that the -1.7 CD11b promoter contains the regulatory elements sufficient for high-level macrophage expression. This promoter should be useful for targeting heterologous gene expression to mature myeloid cells.     

Interleukin-2 induction of lymphokine-activated killer (LAK) activity in the peripheral blood and bone marrow of acute leukemia patients: II. Feasibility of LAK generation in children with active disease and in remission

Activation and expansion in culture with rIL-2 of peripheral blood (PB) and/or bone marrow (BM) specimens derived from children with ALL and ANLL, with active disease (AP) and in remission were studied (RP). Baseline NK cytolytic activity from AP was found to be depressed, whereas RP-derived cells had normal NK activity, as assayed against K562 targets. Culture in rIL-2 significantly enhanced the NK activity of both AP- and RP-derived cells and generated LAK activity, as assayed by 4-hour 51Cr release, against NK-resistant Raji cell line and against fresh, allogeneic, and autologous tumor cells. Lytic activity against fresh, cryopreserved leukemia blasts was of lower than that found against cell lines. In three patients higher lytic activity against autologous than against allogeneic blasts was demonstrated. Expansion in culture with rIL-2 varied from twofold to 120-fold. rIL-2 activation and expansion was better in RP than in AP. The predominant phenotype of activated cells, as determined by flow cytometry, was [mean % (SD)]: CD3- = 54 (12), CD8+ = 55 (17), and NKH1+ = 26 (7). The consistently high level of CD8+ cells was accompanied by very low levels of CD4+ cells: mean = 11% (14). Double-marker analysis showed mean of 33% (10) for CD3+/NKH1+ cells and mean = 32 (11) for CD8+/NKH1+ cells, implying that these populations were overlapping. Kinetics of expression of cell surface markers during 2 to 3 weeks in culture showed that CD8+ and NKH1+ enrichment occurred during the first week and lasted for up to 4 weeks, whereas CD4+ expression decreased after the second week. A significant decrease in the expression of IL-2 receptors (CD25) was observed from the second week of culture. This study shows the feasibility of in vitro generation of killer cells from PB and BM of pediatric leukemia patients.     

Evaluation of Alternatives to Winter Closure of Black Sea Bass Pot Gear: Projected Impacts on Catch and Risk of Entanglement with North Atlantic Right Whales Eubalaena glacialis

Time–area closures have been widely used in fisheries management to prevent overfishing and reduce the bycatch of protected species. Due to quota overages and concerns about entanglement of federally protected North Atlantic right whales Eubalaena glacialis, the commercial harvest of Black Sea Bass Centropristis striata using pot gear has been prohibited in the southeastern United States in winter since 2009. Following the rebuilding of the Black Sea Bass stock and a change to the start date of the fishing year, the South Atlantic Fishery Management Council (SAFMC) increased the commercial annual catch limit (ACL) and is considering twelve alternatives to the pot gear closure that would revise the timing and/or spatial extent of the closure. Changes to this closure could affect the annual catch of Black Sea Bass and increase the risk of right whale entanglement in pot gear. Using historical fishing effort, landings, and right whale sightings data, we projected Black Sea Bass landings and the relative risk of right whale entanglement for each closure alternative, expressed in relative risk units (RRU). We predict that the ACL would be caught, resulting in an in-season closure for most of the proposed SAFMC closure alternatives. The relative risk of entanglement, estimated from the spatial and temporal overlap of Black Sea Bass pot gear fishing effort and right whale relative abundance, was lower for some alternatives than for others, and the relative differences between alternatives were consistent among uncertainty scenarios. The SAFMC’s preferred alternative is projected to result in a relatively low increase in risk to North Atlantic right whales (3–15 RRU off North Carolina and 1–12 RRU off Florida–South Carolina). This framework demonstrates the use of temporally dynamic spatial overlays in assessing the impacts of time–area closures with multiple objectives.

Received April 23, 2015; accepted January 15, 2016     

Systematic Plan of Evaluation Part II: Assessment of Program Outcomes

As an accrediting agency recognized by the U.S. Department of Education (USDE) and the Council for Higher Education Accreditation (CHEA), the Accreditation Commission for Education in Nursing (ACEN) has established Accreditation Standards and Criteria for the evaluation of nursing programs, including the evaluation of outcomes. This article focuses on the essential components and processes for systematic evaluation of program outcomes, including licensure examination pass rate, program completion rate, and job placement rate.     

Late recovery of awareness in prolonged disorders of consciousness –a cross-sectional cohort study

Purpose: To detect any improvement of awareness in prolonged disorders of consciousness in the long term.

Methods: A total of 34 patients with prolonged disorders of consciousness (27 vegetative state and seven minimally conscious state; 16 males; aged 21–73) were included in the study. All patients were initially diagnosed with vegetative/minimally conscious state on admission to our specialist neurological rehabilitation unit. Re-assessment was performed 2–16?years later using Coma Recovery Scale-Revised.

Results: Although remaining severely disabled, 32% of the patients showed late improvement of awareness evidenced with development of non-reflexive responses such as reproducible command following and localization behaviors. Most of the late recoveries occurred in patients with subarachnoid hemorrhage (5/11, 45.5%). The ages of patients within the late recovery group (Mean?=?45, SD?=?11.4) and non-recovery group (Mean?=?43, SD?=?15.5) were not statistically different (p?=?0.76).

Conclusions: This study shows that late improvements in awareness are not exceptional in non-traumatic prolonged disorders of consciousness cases. It highlights the importance of long-term follow up of patients with prolonged disorders of consciousness, regardless of the etiology, age, and time passed since the brain injury. Long-term follow up will help clinicians to identify patients who may benefit from further assessment and rehabilitation. Although only one patient achieved recovery of function, recovery of awareness may have important ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

• Implications for rehabilitation

• Long-term regular follow-up of people with prolonged disorders of consciousness is important.

• Albeit with poor functional outcomes late recovery of awareness is possible in both traumatic and non-traumatic prolonged disorders of consciousness cases.

• Recovery of awareness has significant clinical and ethical implications especially where withdrawal of artificial nutrition and hydration is considered.

     

Endoscopic features of gastroduodenal Crohn's disease.

The clinical, roentgenographic and endoscopic findings in 14 patients with Crohn's disease of the stomach and/or duodenum are described. To date, this is the largest series of endoscopic findings of Crohn's disease of gastroduodenal region. The endoscopic findings include (1) mucosal nodularity or "cobblestoned" mucosa; (2) multiple aphthous-like ulcerations and/or linear ulcerations; (3) thickening of the antral folds; (4) antral narrowing with evidence of hypoperistalsis; (5) duodenal strictures. The diagnosis of gastric duodenal Crohn's disease is achieved by combining recognition of clinical features and roentgenographic and endoscopic features. The endoscopic features correlate well with the roentgenographic findings in our 14 patients. Tissue for histological diagnosis of Crohn's disease of the gastroduodenal area is rarely obtained by endoscopic biopsy, but peroral suction biopsy specimens may increase the rate of histological confirmation.     

Chromosome 17p deletions and p53 gene mutations associated with the formation of malignant neurofibrosarcomas in von Recklinghausen neurofibromatosis.

von Recklinghausen neurofibromatosis (NF1) is a common hereditary disorder characterized by neural crest-derived tumors, particularly benign neurofibromas whose malignant transformation to neurofibrosarcomas can be fatal. The NF1 gene has been mapped to a small region of chromosome 17q, but neither the nature of the primary defect nor the mechanisms involved in tumor progression are understood. We have tested whether NF1 might be caused by the inactivation of a tumor suppressor gene on 17q, analogous to that on chromosome 22 in NF2, by searching for deletions of chromosome 17 in NF1-derived tumor specimens. Both neurofibrosarcomas from patients with "atypical" NF and 5 of 6 neurofibrosarcomas from NF1 patients displayed loss of alleles for polymorphic DNA markers on chromosome 17. However, the common region of deletion was on 17p and did not include the NF1 region of 17q. Since no loss of markers on chromosome 17 was observed in any of 30 benign tumors from NF1 patients, the 17p deletions seen in neurofibrosarcomas are probably associated with tumor progression and/or malignancy. This region contains a candidate gene for tumor progression, p53, which has recently been implicated in the progression of a broad array of human cancers. In a preliminary search for p53 aberrations by direct sequencing of polymerase chain reaction-amplified DNA from 7 neurofibrosarcomas, 2 tumors that contained point mutations in exon 4 of the p53 gene were found, suggesting a role for this gene in at least some neurofibrosarcomas. Thus the formation of malignant neurofibrosarcomas may result from several independent genetic events including mutation of the NF1 gene, whose mechanism of tumorigenesis remains uncertain, and subsequent loss of a "tumor suppressor" gene on 17p, most likely p53.