Components of histidine transport: histidine-binding proteins and hisP protein

The high-affinity (K(m) = 3 x 10(-8) M) transport system for histidine in Salmonella typhimurium has been resolved into three components: J, K, and P. J, which is a histidine-binding protein released by osmotic shock, is specified by the hisJ gene: hisJ mutants lack the binding protein and are defective in histidine transport. Another class of mutants-dhuA, which is closely linked to hisJ-has five times the normal level of binding protein and has an increased rate of histidine transport. P, which is a protein specified by the hisP gene, is required for J binding protein to be operative in transport. hisP mutants, though defective in transport, have normal levels of J binding protein. K, a third transport component, works in parallel to J, and also requires the P protein in order to be operative in transport. A second histidine-binding protein has been found but its relation to K is unclear. hisJ, dhuA, and hisP have been mapped and are in a cluster (near purF) on the S. typhimurium chromosome.     

Mouse NK cell-mediated rejection of bone marrow allografts exhibits patterns consistent with Ly49 subset licensing

Natural killer (NK) cells can mediate the rejection of bone marrow allografts and exist as subsets based on expression of inhibitory/activating receptors that can bind MHC. In vitro data have shown that NK subsets bearing Ly49 receptors for self-MHC class I have intrinsically higher effector function, supporting the hypothesis that NK cells undergo a host MHC-dependent functional education. These subsets also play a role in bone marrow cell (BMC) allograft rejection. Thus far, little in vivo evidence for this preferential licensing across mouse strains with different MHC haplotypes has been shown. We assessed the intrinsic response potential of the different Ly49(+) subsets in BMC rejection by using β2-microglobulin deficient (β2m(-/-)) mice as donors. Using congenic and allogeneic mice as recipients and depleting the different Ly49 subsets, we found that NK subsets bearing Ly49s, which bind "self-MHC" were found to be the dominant subset responsible for β2m(-/-) BMC rejection. This provides in vivo evidence for host MHC class I-dependent functional education. Interestingly, all H2(d) strain mice regardless of background were able to resist significantly greater amounts of β2m(-/-), but not wild-type BMC than H2(b) mice, providing evidence that the rheostat hypothesis regarding Ly49 affinities for MHC and NK-cell function impacts BMC rejection capability.     

Nodding syndrome in Mundri county,South Sudan: environmental,nutritional and infectious factors

Background

Nodding Syndrome is a seizure disorder of children in Mundri County, Western Equatoria, South Sudan. The disorder is reported to be spreading in South Sudan and northern Uganda.

Objective

To describe environmental, nutritional, infectious, and other factors that existed before and during the de novo 1991 appearance and subsequent increase in cases through 2001.

Methods

Household surveys, informant interviews, and case-control studies conducted in Lui town and Amadi village in 2001–2002 were supplemented in 2012 by informant interviews in Lui and Juba, South Sudan.

Results

Nodding Syndrome was associated with Onchocerca volvulus and Mansonella perstans infections, with food use of a variety of sorghum (serena) introduced as part of an emergency relief program, and was inversely associated with a history of measles infection. There was no evidence to suggest exposure to a manmade neurotoxic pollutant or chemical agent, other than chemically dressed seed intended for planting but used for food. Food use of cyanogenic plants was documented, and exposure to fungal contaminants could not be excluded.

Conclusion

Nodding Syndrome in South Sudan has an unknown etiology. Further research is recommended on the association of Nodding Syndrome with onchocerciasis/mansonelliasis and neurotoxins in plant materials used for food.     

Personal barriers to antiretroviral therapy adherence: case studies from a rural Uganda prospective clinical cohort

Background

Although good adherence to antiretroviral therapy (ART) is essential for successful treatment outcomes, some patients may have specific personal barriers to ART adherence.

Objectives

To study specific personal barriers to ART adherence.

Methods

Quantitative data on patients'' health status, ART adherence, CD4 cell counts and viral loads were collected, and qualitative data on life experiences of five patients with poor ART outcomes and adherence were also collected.

Results

Out of 35 patients with poor immunological and virological ART outcomes, 17 (49%) also had poor ART adherence. Patient 1 had no living child and did not disclose her HIV serostatus to her spouse because she wanted to have a child. Patient 2 was an orphan with neither social nor family support. Patient 3 stopped ART when she conceived, returned to the study clinic when pregnant again and was sickly. She was switched to second-line ART with satisfactory outcomes. Patient 4, a 14 year old orphan had missed ART for 2 months when his treatment supporter was away. Patient 5 aged 66 years stopped ART which he blamed for his erectile dysfunction.

Conclusion

ART adherence counselling should target specific personal barriers to ART adherence like: lack of family support, health and sexual life concerns, desire to have children and family instability.     

Analysis of the direct cost of surgery for four diagnostic categories of adult spinal deformity

Background contextExisting literature on adult spinal deformity (ASD) offers little guidance regarding an evidence-based approach to care. To optimize the value of medical treatment, a thorough understanding of the cost of surgical treatment for ASD is required.PurposeTo evaluate four clinically and radiographically distinct groups of ASD and identify and compare the cost of surgical treatment among the groups.Study design/settingMulticenter retrospective study of consecutive surgeries for ASD.Patient sampleThree hundred twenty-five consecutive ASD patients treated between 2008 and 2010.Outcome measuresCost data were collected from hospital administrative records on the direct costs (DCs) incurred for the episode of surgical care, excluding overhead.MethodsBased on preoperative radiographs and history, patients were categorized into one of four diagnostic categories of deformity: primary idiopathic scoliosis (PIS), primary degenerative scoliosis (PDS), primary sagittal plane deformity (PSPD), and revision (R). Analysis of variance and generalized linear model regressions were used to analyze the DCs of surgery and to assess differences in costs across the four diagnostic categories considered.ResultsSignificant differences were observed in DC of surgery for different categories of ASD, with surgical treatment for PDS the most expensive followed in decreasing order by PSPD, PIS, and R (p<.01). Results further revealed a significant positive relationship between age and DC (p<.01) and a significant positive relationship between length of stay and DC (p<.01). Among PIS patients, for every incremental increase in levels fused, the expected DC increased by $3,997 (p=.00). Fusion to pelvis also significantly increased the DC of surgery for patients aged 18 to 29 years (p<.01) and 30 to 59 years (p<.01) but not for 60 years or more (p=.86).ConclusionsThere is an increasing DC of surgery with increasing age, length of hospital stay, length of fusion, and fusions to the pelvis. Revision surgery is the least expensive surgery on average and should therefore not preclude its consideration from a pure cost perspective.     

Analysis of a Statewide Early Intervention Program for Young Children with ASD

Journal of Autism and Developmental Disorders - We evaluated the effectiveness of a statewide Medicaid program providing in-home Early Intensive Behavioral Intervention services to young children...