Discovery of LFF571: an investigational agent for Clostridium difficile infection

Clostridium difficile (C. difficile) is a Gram positive, anaerobic bacterium that infects the lumen of the large intestine and produces toxins. This results in a range of syndromes from mild diarrhea to severe toxic megacolon and death. Alarmingly, the prevalence and severity of C. difficile infection are increasing; thus, associated morbidity and mortality rates are rising. 4-Aminothiazolyl analogues of the antibiotic natural product GE2270 A (1) were designed, synthesized, and optimized for the treatment of C. difficile infection. The medicinal chemistry effort focused on enhancing aqueous solubility relative to that of the natural product and previous development candidates (2, 3) and improving antibacterial activity. Structure-activity relationships, cocrystallographic interactions, pharmacokinetics, and efficacy in animal models of infection were characterized. These studies identified a series of dicarboxylic acid derivatives, which enhanced solubility/efficacy profile by several orders of magnitude compared to previously studied compounds and led to the selection of LFF571 (4) as an investigational new drug for treating C. difficile infection.     

Nationwide shifts in the double burden of overweight and underweight in Vietnamese adults in 2000 and 2005: two national nutrition surveys

Background  

In developing countries, overweight prevalence is increasing while underweight prevalence is still high. This situation is known as the double nutrition burden. Both underweight and overweight are related to increased risk of chronic non-communicable diseases, reduced well-being and quality of life. This study aims to compare the prevalence of overweight and underweight among Vietnamese adults in 2000 and 2005.     

Intervention mapping for development of a participatory return-to-work intervention for temporary agency workers and unemployed workers sick-listed due to musculoskeletal disorders

Background  

In the past decade in activities aiming at return-to-work (RTW), there has been a growing awareness to change the focus from sickness and work disability to recovery and work ability. To date, this process in occupational health care (OHC) has mainly been directed towards employees. However, within the working population there are two vulnerable groups: temporary agency workers and unemployed workers, since they have no workplace/employer to return to, when sick-listed. For this group there is a need for tailored RTW strategies and interventions. Therefore, this paper aims to describe the structured and stepwise process of development, implementation and evaluation of a theory- and practise-based participatory RTW program for temporary agency workers and unemployed workers, sick-listed due to musculoskeletal disorders (MSD). This program is based on the already developed and cost-effective RTW program for employees, sick-listed due to low back pain.     

Structured peer group supervision of school consultation:A case study

Structured peer group supervision (SPGS) supports applied skill growth for novice mental health professionals. Whereas previous SPGS research has focused on counseling, consultation is a core competency for school psychologists, with unique features meriting consideration during SPGS. This case study describes the influence of SPGS on applied communication and problem-solving skills of nine graduate students taking a school consultation course. Structured interviews measured participants’ perceptions, including information about how SPGS influenced consultation skills. Thematic coding revealed positive impacts of SPGS on communication skill development, and as logistical and conceptual support. Implications for school consultation training and practice are discussed.     

Factor V Leiden mutation in one family of Chinese origin

Objective　To investigate the factor V Leiden mutation associated with activated protein C resistance (APCR) in Chinese. Methods　Thirty “normal' individuals and twenty patients with thrombotic disease from Chinese Han Nationality were studied with APTT±APC, PCR followed by MnLI restriction enzyme analysis,PCR based direct sequence-specific primers (PCR-SSP) and DNA sequence analysis. Results　In one healthy control, the activated protein C (APC) sensitivity ratio (SR) was found to be significantly lower (0.8) than that in other normal control (>2.0). This individual was identified to be heterozygous for FV Leiden mutaiton (Arg506-Gln). His grand-uncle, father, brother and son were also identified to be heterozygous for FV Leiden. The APC resistance was found in 3 other cases of thrombotice diseases, but with no FV Leiden mutation. Conclusion　This is the first four generations family case of FV Leiden mutation associated with APCR reported within Chinese ethnic population. It is note-worthy that more FV Leiden or whether other gene defects may be associated with APC resistance and acquired APCR causing thrombosis in Chinese population.     

In situ hybridization histochemistry localization of interleukin-3 mRNA in mouse brain

The hematopoietic growth factor interleukin-3 (IL-3) promotes the proliferation and maturation of pluripotent myeloid progenitor cells. In the immune system, IL-3 is synthesized by mitogen or antigen- stimulated T lymphocytes. We demonstrate the expression of IL-3 mRNA in mouse brain by in situ hybridization histochemistry and Northern blot analysis. The IL-3 mRNA is localized in discrete areas of the brain and can be found in neuronal cell body and astrocytes. Northern analysis of cerebellar RNA, compared with mRNA extracted from WEHI-3 cells, showed a single hybridization band, approximately 1.2 kb, suggesting similar processing between brain and myeloid cells. The molecular evidence and previous observations of IL-3-like biologic activity found in the brain suggest a potential role for IL-3 in the neurobiology of the CNS.