Different Treatment Modalities for the Management of Spinal Tuberculosis

Objective: To study the rationale of different treatment modalities of caries spine, anti tuberculus therapy (ATT), abscess drainage, spinal cord decompression and stabilisation.Materials and Methods: In this descriptive study number of patients were 132 conducted in the department of neurosurgery Lady Reading Hospital, Peshawar. From Dec.2008 to Dec. 2012.Results: Local spinal pain was relieved in 98.5%, tenderness improved in 97.7%, Paresis and plegia in 81.1%, Kypotic deformity reduced in 43.2%, approved sphincter functions improved in 40.6% cases. Morbidity was 2.3% and mortality (0.8%). Surgical procedure was abscess drainage in 8% and anterior decompression and stabilization was in 61% cases. All patients were treated with standard ATT regimen 4 drugs for 2 to 3 months and 3 drugs for 10 – 16 months and analgesics and followed for 18 months. Male were 83 (62.9%), female 49 (37.1%) minimum age 3years, maximum 70 years and mean ± SD 30 ± 15 years. Inclusion criteria: Patients hav-ing spinal TB. Exclusion criteria: Spinal pyogenic infection, metastasis and metabolic bone diseases. Informed consent and ethical committee approval was taken. Diagnosis was made on history and clinical examination of local tenderness, kyphotic deformity, paraparesis / plegia, tetraparesis / plegia and sphincter dysfunction. Investi-gations were x-ray chest, spine 3D CT and MRI. Erythrocyte sedimentation rate (ESR) and biopsy of the necrotic materials were done. Patients were treated with stanandard ATT, neurological improvement and radiological stability was assessed. Patients were divided in Group – A: Only ATT or abscesses drainage and ATT. Group-B: Spinal decompression and stabilisation with ATT. All information were recorded on a proforma. Data was analyzed using SPSS version 19.Conclusions: Early diagnosis and treatment had excellent outcome. Dorso-lumbar spine involvement and young age was common. Advanced cases needs multimodal therapy (medical, surgical and supportive). Some degree of kyphotic deformity still remained

The outcomes of dapagliflozin use in real-life clinical settings in endocrinology clinics of Islamabad, Pakistan

Introduction: Dapagliflozin is a member of a novel class of drugs (sodium-glucose cotransporter-2 inhibitors) used to treat type 2 diabetes mellitus and licensed in Pakistan in 2017. This retrospective observational study evaluated the effects of dapagliflozin on glycated hemoglobin (HbA1c) concentrations in patients treated at endocrinology clinics in Islamabad, Pakistan. The secondary objectives included assessing the effects of dapagliflozin on weight reduction and blood pressure control and to determining its safety.Methodology: Patients with type 2 diabetes who were treated with dapagliflozin were identified by screening the electronic medical records at tertiary care hospitals in Islamabad. Data were collected at the first visit and at follow-up. Categorical variables were recorded as frequencies and percentages and compared by McNemar’s tests, and continuous variables were recorded as means and standard deviations and compared by paired sample t-tests.Results: Mean HbA1C concentration was significantly lower at follow-up than at the first visit (7.57%±0.98% vs. 9.07%±2.07%, respectively; p\u3c0.001). Bodyweight (85.09±15.92 kg vs. 87.07±16.11 kg, respectively; p\u3c0.001) and diastolic blood pressure (80.34±7.12 mmHg vs. 82.34±9.61 mmHg, respectively; p\u3c0.001) were also significantly lower at follow-up than at the first visit, whereas systolic pressure showed a marginally significant reduction (123.5±16.57 mmHg vs. 126.83±19.97 mmHg, p=0.048).Conclusion: This first observational study of patients in Pakistan treated with dapagliflozin found that HbA1c concentration, weight, and blood pressure were reduced after initiation of dapagliflozin treatment

Fabrication and Electrical characteristic of quaternary ultrathin HfTiErO thin films for MOS devices grown by rf sputtering

Ultra-thin Ti and Er co-doped HfO2 films were grown on Si substrate by RF sputtering at different compositions and subjected to rapid thermal annealing at 500?°C and 700?°C in nitrogen ambient for 60 s. Dielectric properties of ultrathin co doped with Tritium and Erbium into hafnium oxide (HfO2) with rapid thermal annealing (RTA) have been investigated. Ti and Er different contents doped HfO2 thin films about (5 to 10) nm thicknesses have been employed for Au/HfTiErO/Si/Au metal oxide semiconductor (MOS) structures fabrication. The fabricated MOS (Au/HfTiErO/Si/Au) structure has been used for extracting electrical properties such that, dielectric constant, effective charge carriers, flat band voltage, interface trap density and doping concentration through capacitance voltage measurements. The films compared at different contents used for Ti and Er doped with HfO2 on growth parameters, which could not showed excellent properties due to small thickness and other several defects during the depositions. While, the film annealed at 500?°C has the improved microstructure and electrical characteristics. Furthermore Atomic force microscopy and X-ray photo electron microscopy analysis verified the microstructure of HfTiErO gate oxide for future MOS devices.   Keywords: high-k, HfTiErO, Thin films, rf Sputterin

Role of Chaperone Mediated Autophagy (CMA) in the Degradation of Misfolded N-CoR Protein in Non-Small Cell Lung Cancer (NSCLC) Cells

Nuclear receptor co-repressor (N-CoR) plays important role in transcriptional control mediated by several tumor suppressor proteins. Recently, we reported a role of misfolded-conformation dependent loss (MCDL) of N-CoR in the activation of oncogenic survival pathway in acute promyelocytic leukemia (APL). Since N-CoR plays important role in cellular homeostasis in various tissues, therefore, we hypothesized that an APL like MCDL of N-CoR might also be involved in other malignancy. Indeed, our initial screening of N-CoR status in various leukemia and solid tumor cells revealed an APL like MCDL of N-CoR in primary and secondary tumor cells derived from non-small cell lung cancer (NSCLC). The NSCLC cell specific N-CoR loss could be blocked by Kaletra, a clinical grade protease inhibitor and by genistein, an inhibitor of N-CoR misfolding previously characterized by us. The misfolded N-CoR presented in NSCLC cells was linked to the amplification of ER stress and was subjected to degradation by NSCLC cell specific aberrant protease activity. In NSCLC cells, misfolded N-CoR was found to be associated with Hsc70, a molecular chaperone involved in chaperone mediated autophagy (CMA). Genetic and chemical inhibition of Lamp2A, a rate limiting factor of CMA, significantly blocked the loss of N-CoR in NSCLC cells, suggesting a crucial role of CMA in N-CoR degradation. These findings identify an important role of CMA-induced degradation of misfolded N-CoR in the neutralization of ER stress and suggest a possible role of misfolded N-CoR protein in the activation of oncogenic survival pathway in NSCLC cells

Role of Misfolded N-CoR Mediated Transcriptional Deregulation of Flt3 in Acute Monocytic Leukemia (AML)-M5 Subtype

The nuclear receptor co-repressor (N-CoR) is a key component of the generic multi-protein complex involved in transcriptional control. Flt3, a key regulator of hematopoietic cell growth, is frequently deregulated in AML (acute myeloid leukemia). Here, we report that loss of N-CoR-mediated transcriptional control of Flt3 due to misfolding, contributes to malignant growth in AML of the M5 subtype (AML-M5). An analysis of hematopoietic genes in AML cells led to the identification of Flt3 as a transcriptional target of N-CoR. Flt3 level was inversely related to N-CoR status in various leukemia cells. N-CoR was associated with the Flt3 promoter in-vivo, and a reporter driven by the Flt3 promoter was effectively repressed by N-CoR. Blocking N-CoR loss with Genistein; an inhibitor of N-CoR misfolding, significantly down-regulated Flt3 levels regardless of the Flt3 receptor mutational status and promoted the differentiation of AML-M5 cells. While stimulation of the Flt3 receptor with the Flt3 ligand triggered N-CoR loss, Flt3 antibody mediated blockade of Flt3 ligand-receptor binding led to N-CoR stabilization. Genetic ablation of N-CoR potentiated Flt3 ligand induced proliferation of BA/F3 cells. These findings suggest that N-CoR-induced repression of Flt3 might be crucial for limiting the contribution of the Flt3 signaling pathway on the growth potential of leukemic cells and its deregulation due to N-CoR loss in AML-M5, could contribute to malignant growth by conferring a proliferative advantage to the leukemic blasts. Therapeutic restoration of N-CoR function could thus be a useful approach in restricting the contribution of the Flt3 signaling pathway in AML-M5 pathogenesis

Akt-Induced Phosphorylation of N-CoR at Serine 1450 Contributes to Its Misfolded Conformational Dependent Loss (MCDL) in Acute Myeloid Leukemia of the M5 Subtype

10.1371/journal.pone.0070891PLoS ONE88-POLN

Optical high-speed Schlieren imaging arrangement for visualizing non-linear ultrasound phenomena within an ultrasound drug delivery system

The aim of this project was to establish a schlieren imaging system (SIS) which was coupled with a high-speed camera (HSC). For assembling SIS, a number of optical components were arranged. Later on, additional optical components were added to achieve high quality SIS with image sensitivity. The goals were to visualize the gas flow in air using SIS, and then to visualize the density disturbances in water due to propagation of ultrasound (kPa to MPa range), and the shock waves (MPa range) in an ultrasound drug delivery system. In addition, other non-linear phenomena were observed. For example, a cavitation bubble collapse was visible in the images. The frame rate of HSC was used up to 800,000 fps. Furthermore, the visual information in the schlieren images was calibrated to show spatial pressure distributions in SI units (pascals) in water. Based on the literature review, several SIS models, and systems were studied. Initially, a simple SIS was designed. For assembling the SIS, optical components were arranged. The assembled SIS was used for visualizing the images. The SIS was modified time to time by adding a cage lens system, a focusing lens, and a 3D rotational assembly. In the modified SIS, more optical components were added that resulted in better sensitivity, image contrast, and field uniformity in the images. Using SIS, the visibility of the cavitation bubble collapse in the images, visualization of the shock waves, ultrasonic pressure measurement were successfully performed. In conclusion, the proposed SIS was assembled, and then modified with the addition of more optical components. The modified SIS worked-well in achieving the best visualization of the images in terms of image contrast, image sensitivity, and field uniformity in the images