Better education for better health care

In India, all national nutrition programs and activities are carried out by staff at the primary health centers under the leadership of medical officers. A study of 114 of these officers from 80 primary health centers in rural districts of Andhra Pradesh State was undertaken to assess their knowledge and performance, particularly with regard to nutrition and related matters. Scores were expressed in percentages, with under 50% considered poor, 50-75% satisfactory, and over 75% good. The highest score 67.7% was obtained on knowledge of nutrition and related areas, and the lowest, 19.7% was for the participant's awareness of their own job responsibilities. Although overall theoretical knowledge on nutrition and related matters was satisfactory, significant gaps existed. A majority were ignorant as to how many people were covered by their centers and the numbers of staff in different categories, suggesting little attention was being given to planning and implementation of various services. Only 23% were aware of their own responsibilities regarding nutrition, and only 16% mentioned teaching nutrition during their training programs. The conclusion is that the medical education system must be better coordinated with the health care delivery infrastructure. Medical undergraduates need more exposure to Practical aspects of health care in rural communities, managerial aspects of work in primary health centers, and programs with a stronger nutrition component. In addition, refresher courses must be offered, and the problem of overburdening the medical officers must be dealt with.     

Anthropometric measurements,deficiency signs and their relationship under drought conditions

In October-November 1987 in India, the Desert Medicine Research Centre in Jodhpur conducted a rapid anthropometric survey of 555 preschool children in 4 districts of Rajasthan which had been severely affected by drought (Jodhpur, Jalore, Nagpur, and Barmer districts) to determine the association between anthropometric measurements and various nutritional deficiency signs and infections. Based on weight for age, 82.3% of the children were undernourished. 13.3% of all children were severely malnourished (grade III undernutrition). Anemia, protein energy malnutrition (PEM), and upper respiratory infections occurred significantly more often as one digressed from the normal nutrition grade. These 3 conditions were also closely linked to weight status. Based on height for age, 62.4% of the children were chronically undernourished. 11.9% of all children were severely so. PEM was the only deficiency sign or infection associated with height status (6.2% of children with normal nutrition had PEM vs. 15.% for grade I undernutrition and 34.8% for grade II undernutrition; p .001). Vitamin A deficiency, anemia, and PEM occurred more frequently as one went from normal nutrition to grade II undernutrition based on fat fold at triceps (FFT) measurements. PEM and upper respiratory infections were significantly associated with weight for height status. Weight correctly identified 84% of all nutritional deficiency signs and infections. The corresponding figures for height, FFT, and weight for height were 64.2%, 75.4%, and 31%. Thus, weight was the most sensitive screening measurement in identifying nutritional deficiency signs and infections. Based on weight alone, the odds ratio of undernourished children developing Vitamin b-complex deficiency, PEM, and upper respiratory infections was 1.58, 3.25, and 1.77, respectively. Weight for height was the most specific screening measurement (88.2% vs. 44.7% for height, 29.3% for FFT, and 26.1% for weight).     

A novel predictor of clinical response to methotrexate in patients with rheumatoid arthritis: a pilot study of in vitro T cell cytokine suppression

OBJECTIVE: Methotrexate (MTX) is an important drug for treatment of rheumatoid arthritis; however, there is variation in the clinical response. MTX inhibits T cell cytokine production, with significant interindividual variability in the dose required. We investigated if the variability in clinical response was related to variability in the in vitro assay. METHODS:Patients with disease modifying antirheumatic drug-naive, active RA [1982 American College of Rheumatology (ACR) criteria] seen from September 2005 through January 2006 were enrolled. MTX was started at 10 mg/week and increased monthly by 2.5 mg/week. Baseline whole-blood cultures were set up with anti-CD3, anti-CD28, and increasing doses of MTX. Supernatants were harvested at 96 hours and tumor necrosis factor-alpha (TNF-alpha), interferon-gamma (IFN-gamma), and interleukin 10 (IL-10) concentrations were estimated by ELISA. The dose of MTX (ID50) required for 50% suppression of production of cytokines and the change in Disease Activity Score-28 (DeltaDAS) at 4 months were noted. RESULTS: T cell stimulation resulted in significant increase in cytokine release, and addition of MTX led to a dose-dependent suppression of all 3 cytokines. There was significant negative correlation of DeltaDAS with ID50 values for TNF-alpha (R = -0.62, p < 0.01) and IFN-gamma (R = -0.43, p = 0.04). At 4 months, EULAR moderate and ACR 20% responses were achieved by 13 and 16 patients, respectively. EULAR moderate response could be predicted using ROC curves for TNF-alpha (sensitivity 93%, specificity 86%) and IFN-gamma (60% specificity, 71% sensitivity). ACR response was correctly predicted in 14 of 16 ACR 20% responders and in all ACR 50% and ACR 70% responders. CONCLUSION: An in vitro TNF-alpha suppression assay may help predict clinical response to MTX in RA.     

Pre-Hospital Diagnosis in Mobile Stroke Unit

ObjectivesMobile stroke unit (MSU) has been shown to rapidly provide pre-hospital thrombolysis in acute ischemic stroke (AIS). MSU encounters neurological disorders other than AIS that require emergent treatment.Methods/MaterialsWe obtained pre-hospital diagnosis and treatment data from the prospectively collected dataset on 221 consecutive MSU encounters. Based on initial clinical evaluation and neuroimaging obtained on MSU, the diagnosis of AIS (definite, probable, and possible AIS, transient ischemic attack), intracranial hemorrhage, and likely stroke mimics was made.ResultsFrom July 2014 to April 2015, 221 patients were treated on MSU. 78 (35%) patients had initial clinical diagnosis of definite/probable AIS or TIA, 69 (31%) were diagnosed as possible AIS or TIA, 15 (7%) had intracranial hemorrhage while 59 patients (27%) were diagnosed as likely stroke mimics. Stroke mimics encountered included 13 (6%) metabolic encephalopathy, 11 (5%) seizures, 9 (4%) migraines, 3 (1%) substance abuse, 2 (1%) CNS tumor, 3 (1%) infectious etiology and 3 (1%) hypoglycemia. Fifty-four (24%) patients received non-thrombolytic treatments on MSUConclusionAbout one third of MSU encounters were not AIS initially, including intracranial hemorrhage and stroke mimics. MSU can be utilized to provide pre-hospital treatments in emergent neurological conditions other than AIS.     

Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases

OBJECTIVE: Cytokines are the major mediators of joint damage in chronic arthritis. Data on synovial fluid (SF) concentration of Th17 cell-derived cytokine interleukin 17 (IL-17) in patients with juvenile idiopathic arthritis (JIA) are sparse. We measured levels of IL-17 in SF specimens from children with enthesitis-related arthritis (ERA) and polyarticular JIA (poly-JIA), and studied the ability of IL-17 to produce matrix metalloproteinases (MMP) and cytokines by fibroblast-like synoviocytes (FLS) from patients with ERA. METHODS: IL-17 levels were measured in SF of patients with ERA (n = 43), poly-JIA (n = 17), rheumatoid arthritis (RA; n = 35), and osteoarthritis (OA; n = 10) by ELISA. In patients with JIA, 10 paired serum samples were also assayed. FLS were cultured from SF of patients with ERA and subsequently stimulated for 48 h by IL-17 or tumor necrosis factor-alpha. Later the production of IL-6, IL-8, MMP-1, MMP-3, and tissue inhibitor of metalloproteinase (TIMP)-1 was measured in the culture supernatants by ELISA. RESULTS: Median IL-17 levels in SF were higher in patients with JIA [28 pg/ml (range 0-200)] compared to OA [0 pg/ml (range 0-84); p < 0.001] and RA (p < 0.05). The levels were comparable between poly-JIA patients and the ERA group. The median SF IL-17 levels were significantly higher compared to serum levels in children with JIA (p < 0.005). In ERA, SF IL-17 correlated with number of swollen joints (r = 0.35; p < 0.05), number of joints with limited mobility (r = 0.55; p < 0.001), and number of tender joints (r = 0.46; p < 0.01); however, no correlation was seen with erythrocyte sedimentation rate. IL-17 induced FLS to produce IL-6, IL-8, MMP-3, and MMP-1. However, there was no effect on the production of TIMP. CONCLUSION: Increased IL-17 levels in ERA SF correlate with disease activity and this may be due to increased production of MMP and cytokines by IL-17.     

The proteasomal subunit Rpn6 is a molecular clamp holding the core and regulatory subcomplexes together

Proteasomes execute the degradation of most cellular proteins. Although the 20S core particle (CP) has been studied in great detail, the structure of the 19S regulatory particle (RP), which prepares ubiquitylated substrates for degradation, has remained elusive. Here, we report the crystal structure of one of the RP subunits, Rpn6, and we describe its integration into the cryo-EM density map of the 26S holocomplex at 9.1?? resolution. Rpn6 consists of an α-solenoid-like fold and a proteasome COP9/signalosome eIF3 (PCI) module in a right-handed suprahelical configuration. Highly conserved surface areas of Rpn6 interact with the conserved surfaces of the Pre8 (alpha2) and Rpt6 subunits from the alpha and ATPase rings, respectively. The structure suggests that Rpn6 has a pivotal role in stabilizing the otherwise weak interaction between the CP and the RP.     

A novel device for safe exteriorization of haptic in scleral fixation intraocular lens surgery

The aim of this study was to describe a novel device that has been designed to facilitate anterior segment and novice surgeons to perform extraocular needle-guided haptic insertion technique (X-NIT) for scleral fixation intraocular lens surgery (SFIOL). We performed SFIOL surgery using X-NIT device in 21 eyes of 21 patients. The mean preoperative best-corrected visual acuity (BCVA) was 0.5 ± 0.2 logarithm of minimum angle of resolution (log MAR), which improved by one or more lines postoperatively in all eyes. There were no intraoperative complications. Postoperatively, we noted minimal corneal edema in one patient and dispersed vitreous hemorrhage in one patient. The sharpness and angulation of the needle and the haptic holding ability of silicone stopper were found to be satisfactory. The X-NIT device may potentially improve the safety of SFIOL procedures by minimizing intraocular maneuvers.