Evaluating the use of locally-based health facility assessments in Afghanistan: a pilot study of a novel research method

Background

Through the Balanced Scorecard program there have been independent, annual and nationwide assessments of the Afghan health system from 2004 to 2013. During this period, Afghanistan remained in a dynamic state of conflict, requiring innovative approaches to health service evaluation in insecure areas. The primary objective of this pilot study was to evaluate the reliability of health facility assessments conducted by a novel, locally-based data collection method compared to a standard survey team.

Methods

In this cross-sectional study, one standard survey team of clinicians and multiple rapidly trained locally-based survey teams of teachers conducted health facility assessments in Badghis province, Afghanistan from March – August, 2010. Outpatient facilities covered under the country’s Basic Package of Health Services were eligible for inclusion. Both approaches attempted to survey as many health facilities as safely possible, up to 25 total facilities per method. Each facility assessed was scored on 23 health services indicators used to evaluate performance in the annual Balanced Scorecard national assessment. For facilities assessed by both survey methods, the indicator scores produced by each method were compared using Spearman’s correlation coefficients and linear regression analysis with generalized estimating equations.

Results

The standard survey team was able to assess 11 facilities; the locally-based approach was able to assess these 11 facilities, as well as 13 additional facilities in areas of greater insecurity. Among the 11 facilities assessed by both approaches, 19 of 23 indicators were statistically similar by survey method (p?<?.05). Spearman’s coefficients varied widely from (?0.39) to (0.71). The differences were greatest for items requiring specialized data collector knowledge on reviewing patient records, patient examination and counseling, and health worker reported satisfaction.

Conclusions

This pilot study of a novel method of data collection in health facility assessments showed that an approach using locally-based survey teams provided markedly increased access to areas of insecurity. Though analysis was limited by small sample size, indicator scores used for facility evaluation were relatively comparable overall, but less reliable for items requiring clinical knowledge or when asking health worker opinions, suggesting that alternative approaches may be needed to assess these parameters in insecure environments.

     

Serial bone mineral density ratio measurement for fixator removal in tibia distraction osteogenesis and need of a supportive method using the pixel value ratio

Distraction osteogenesis is one of the common procedures for limb lengthening. However, attempts are being made constantly to establish objective guidelines for early and safe removal of a fixator using a sensitive and quantitative measurement technique. Dual-energy X-ray absorptiometry (DEXA) has been evaluated in the past for understanding callus stiffness, and the present study is a step further in this direction. The purpose of this study was to evaluate the correlation between bone mineral density ratio (BMDR) obtained by a DEXA scan and the pixel value ratio (PVR) on plain digital radiographs at each cortex and various callus pathways and callus shapes as described by Ru-Li's classification. A retrospective analysis of 40 tibial segments in 23 patients operated upon for various indications for limb lengthening was carried out. There were 11 male and 12 female patients with a mean age of 18 years. The Ilizarov method was applied after monofocal osteotomy, and distraction and consolidation were monitored using digital radiographs and DEXA scanning. BMDR was positively correlated with PVR, and the optimal BMDR for removal of the fixator was found to be 0.511. PVR of all cortices, except the anterior cortex, showed significant positive correlation with BMDR of the regenerate. There was good correlation between BMDR and PVR in the homogenous or heterogenous pathway according to callus shape and pathway. Thus, this study shows that BMD measurement can provide an objective and noninvasive method for assessing the rate of new bone formation during tibial distraction osteogenesis. It can thus function as an effective adjunct to measure callus stiffness, along with PVR, using digital radiographs, especially in cases in which callus maturation and stiffness is doubtful. Further studies especially dealing with callus progression through the lucent pathway as well as those dealing with regenerate fractures may be needed to conclusively prove the efficacy of this method for measurement of callus maturation.     

Overexpressing TNF-Alpha in Pancreatic Ductal Adenocarcinoma Cells and Fibroblasts Modifies Cell Survival and Reduces Fatty Acid Synthesis via Downregulation of Sterol Regulatory Element Binding Protein-1 and Activation of Acetyl CoA Carboxylase

The effect of tumor necrosis factor-alpha (TNF-α) gene delivery has been suggested as a potentially useful therapeutic approach to improve the chemotherapeutic treatment of patients with pancreatic ductal adenocarcinoma (PDA), but the exact mechanism of its action is not clearly understood. In this study, we analyzed the expression profile of TNF-α in PDA tissue and explored its potential role in fatty acid synthase (FAS) regulation in PDA cells and in fibroblasts. Quantitative real-time polymerase chain reaction was used to examine the expression of TNF-α in PDA, matching adjacent tissues, and benign lesions. Logistic regression models with robust variance were used to analyze the gene expression levels, and Kaplan–Meier survival curves were generated. In vitro, we overexpressed the TNF-α gene in PDA cells and fibroblasts and analyzed its effect on cell survival, migration, and on members of the FAS signaling pathway. We also evaluated TNF-α effects on a panel of inflammation-, angiogenesis-, and metastasis-related markers. In the tumor tissue of PDA patients, compared with their matched adjacent tissue, expression levels of TNF-α were not statistically different and did not correlate with survival or any other examined clinicopathological features. Overexpression of TNF-α significantly (p?<?0.05) reduced PDA and fibroblast cell migration. In PDA cells that highly overexpress TNF-α, this was associated with a significant reduction of FAS mRNA and protein expression levels and significant (p?<?0.05) reduction of SREBP-1 and ACC mRNA. Reduction of FAS by TNF-α was inhibited when either SREBP-1 or ACC was knocked down by siRNA. PDA cells and fibroblasts that overexpress TNF-α displayed differential regulation of several inflammation-related markers and reduced levels of metastasis-related genes. Our data demonstrate a previously unknown multi-targeted involvement of TNF-α in PDA lipogenesis and inflammation and metastasis and suggest that intratumoral introduction of TNF-α may have the potential as a novel therapeutic approach in human PDA.     

Influence of gamma-ray irradiation and post-annealing studies on pentacene films: the anisotropic effects on structural and electronic properties

In this work, γ-ray irradiation effects on pentacene thin films are investigated in terms of the change in the crystallinity, and electronic structure as well as chemical states of the film. The pentacene films are γ-irradiated up to 3 kGy and then characterized using synchrotron X-ray diffraction, near edge X-ray absorption fine structure (NEXAFS) and X-ray photoelectron spectroscopy. We found that γ-ray irradiation creates defects, resulting in a decrease of X-ray diffraction intensity both in the plane normal and in-plane directions. From angle dependent NEXAFS; the transition of C 1s to π* orbital for irradiated samples increases; suggesting that the unoccupied π* states enhance due to defects or radical formation in pentacene thin films. Additionally, the in-plane resistivity shows a decreasing trend of resistance after irradiation. This trend of increase in conductivity is also consistent with C 1s to π transition, which manifests the increase in carrier concentration. Hall effect measurements further confirmed the increase in carrier concentration as a function of dose; however, the mobility of the sample decreases as the dose rate increases due to the defects created. By post-irradiation annealing, the thin film phase diffraction intensity can be recovered. Altogether, the anisotropic studies on pentacene films disclosed that the irradiation leads to defect formation along in-plane and plane normal directions. Overall, these results suggest that pentacene is one of the robust organic electronic materials; whose structure remains mostly intact even after irradiation up to a dose of 3 kGy.

In this work, γ-ray irradiation effects on pentacene thin films are investigated in terms of the change in the crystallinity, and electronic structure as well as chemical states of the film.     

Leishmania donovani: Influence of anti-leishmanial therapy on expression of lymphocyte function-associated antigen-3 and its relevance to pathogenisis in visceral leishmaniasis

Lymphocyte function associated antigen 3 (LFA-3) is known as adhesion molecule with its role in T-cell activation signaling as well as in Foxp3 expression. Its influences on IL-10 production is also available, whose role in pathogenesis is well documented. However, this molecule is not yet directly addressed for its association with visceral leishmaniasis (VL). We investigated the relationship between Leishmania donovani infection and expression of LFA-3 in VL patients in their pre and post treatment stage through this case control study. Present study reports L. donovani mediated expression of LFA-3 on CD14⁺ monocytes in human VL. Active cases of VL was observed with 2.91-fold increased mean florescence intensity (MFI) of LFA-3 expression on CD14⁺ cells compared to healthy control (p = 0.0001). This increased MFI of untreated VL cases was reduced 1.92-fold in successfully treated cases (p = 0.0001). This observation was also accorded by mRNA expression for LFA-3 in monocytes of corresponding samples. The expression of LFA-3 was also observed influenced by L. donovani load in splenic aspirates, as it was 1.71-fold elevated in patients with Ld grade ?3+ compared to patients with ?2+ Ld grade (p = 0.0121). To evaluate the possibility that L. donovani utilize LFA-3 mediated evasion pathway in human visceral leishmaniasis; in vitro experiments were performed for measurement of pathogenic cytokine IL-10 and Foxp3 mRNA expression. The IL-10 production and Foxp3 expression in peripheral blood mononuclear cells from VL subjects were observed regulated significantly (p = 0.0131 and 0.0436 when compared with untreated samples) in presence of an antagonist to LFA-3. This study recommends further investigations to strengthen the pathogenic and prognostic significance of LFA-3 in visceral leishmaniasis.     

Myeloid cell–derived PROS1 inhibits tumor metastasis by regulating inflammatory and immune responses via IL-10

Stimulation of TAM (TYRO3, AXL, and MERTK) receptor tyrosine kinases promotes tumor progression through numerous cellular mechanisms. TAM cognate ligands GAS6 and PROS1 (for TYRO3 and MERTK) are secreted by host immune cells, an interaction which may support tumor progression. Here, we revealed an unexpected antimetastatic role for myeloid-derived PROS1: suppressing metastatic potential in lung and breast tumor models. Pros1 deletion in myeloid cells led to increased lung metastasis, independent of primary tumor infiltration. PROS1-cKO bone marrow–derived macrophages (BMDMs) led to elevated TNF-α, IL-6, Nos2, and IL-10 via modulation of the Socs3/NF-κB pathway. Conditioned medium from cKO BMDMs enhanced EMT, ERK, AKT, and STAT3 activation within tumor cells and promoted IL-10–dependent invasion and survival. Macrophages isolated from metastatic lungs modulated T cell proliferation and function, as well as expression of costimulatory molecules on DCs in a PROS1-dependent manner. Inhibition of MERTK kinase activity blocked PROS1-mediated suppression of TNF-α and IL-6 but not IL-10. Overall, using lung and breast cancer models, we identified the PROS1/MERTK axis within BMDMs as a potent regulator of adaptive immune responses with a potential to suppress metastatic seeding and revealed IL-10 regulation by PROS1 to deviate from that of TNF-α and IL-6.     

Biological Basis of Depression in Adults with Diabetes

Diabetes and depression are common comorbid conditions. Although certain health behaviors and risk factors partially explain the association of depression and diabetes, other potential mechanisms have yet to be elucidated. Certain neuroendocrine alterations such as activation of the hypothalamic-pituitary-adrenal (HPA) axis and sympathetic nervous system (SNS) may contribute to the association. Additionally, presence of a proinflammatory state shown in recent literature in both diabetes and depression may contribute to this as well. The objectives of this review are to summarize and review the recent evidence showing alterations of these three biological systems—HPA axis, SNS, and inflammatory cascade—in depression, diabetes, and diabetes-related risk factors.     

How can we optimize the long-term outcome in children with intracranial cavernous malformations? A single-center experience of 61 cases

Neurosurgical Review - The objective is to provide a treatment algorithm for pediatric patients with intracranial cavernous malformations (CMs) based on our experience....