Epidemiologic and socioeconomic factors impacting hepatitis B virus and related hepatocellular carcinoma

Chronic Hepatitis B is a highly prevalent disease worldwide and is estimated to cause more than 800000 annual deaths from complications such as cirrhosis and hepatocellular carcinoma (HCC). Although universal hepatitis B vaccination programs may have reduced the incidence and prevalence of chronic hepatitis B and related HCC, the disease still imposes a significant healthcare burden in many endemic regions such as Africa and the Asia-Pacific region. This is especially concerning given the global underdiagnosis of hepatitis B and the limited availability of vaccination, screening, and treatment in low-resource regions. Demographics including male gender, older age, ethnicity, and geographic location as well as low socioeconomic status are more heavily impacted by chronic hepatitis B and related HCC. Methods to mitigate this impact include increasing screening in high-risk groups according to national guidelines, increasing awareness and health literacy in vulnerable populations, and developing more robust vaccination programs in under-served regions.     

Clinicopathological patterns of bladder carcinoma over 1 year: experience from University Hospital of Nepal

Purpose

To define the clinical and pathological patterns of urinary bladder carcinoma from the University Hospital of Nepal.

Methods

This is a retrospective analytical study. Patients with bladder mass who underwent surgery over 1 year and who had data record were included in the study. Demographic profile, type of surgery, findings on clinical examination, cystoscopy findings, histopathological report, tumor stage, and post-surgery adjuvant therapy were analyzed.

Results

Out of 86 patients who underwent transurethral resection of bladder tumor, 77 patients had biopsy-proven malignant bladder tumor. Urothelial cancer was present in 96.1%. Male were 78.6%. The mean age of diagnosis was 65.5?±?11.8 years. Non-muscle-invasive bladder cancer (NMIBC) was 3.7 times more common than muscle-invasive bladder cancer (MIBC). High-grade tumors (58.6%) were more common than low grade (41.4%). The detrusor muscle was present inthe biopsy specimen of 48 patients (64%). Re-TURBT within 2–6 weeks was considered based on histopathology reports for about half of the patients (45.3%). Upstaging and upgrading of the tumor was present in 5.8 and 5.8% of the patients, respectively. Residual tumor without upstaging and upgrading was present in 23.5%. One patient (1.3%) had Clavien–Dindo grade 1, three (4%) patients had grade 2 and two patients (2.7%) had grade 3b.

Conclusion

In the present study, patients with bladder cancer are younger than reported in other studies. Smokers are strongly predisposed. The histological pattern is similar to the Western and Asian populations. NMIBC and MIBC occur in proportion to that described as in other studies. We had a lower rate of recurrence, upstaging and upgrading. We had a lesser rate of acceptance for radical cystectomy in our patients.

     

Oxygen-inducible glutamate oxaloacetate transaminase as protective switch transforming neurotoxic glutamate to metabolic fuel during acute ischemic stroke

This work rests on our previous report (J Cereb Blood Flow Metab 30: 1275-1287, 2010) recognizing that glutamate (Glu) oxaloacetate transaminase (GOT) is induced when brain tissue hypoxia is corrected during acute ischemic stroke (AIS). GOT can metabolize Glu into tricarboxylic acid cycle intermediates and may therefore be useful to harness excess neurotoxic extracellular Glu during AIS as a metabolic substrate. We report that in cultured neural cells challenged with hypoglycemia, extracellular Glu can support cell survival as long as there is sufficient oxygenation. This effect is abrogated by GOT knockdown. In a rodent model of AIS, supplemental oxygen (100% O(2) inhaled) during ischemia significantly increased GOT expression and activity in the stroke-affected brain tissue and prevented loss of ATP. Biochemical analyses and in vivo magnetic resonance spectroscopy during stroke demonstrated that such elevated GOT decreased Glu levels at the stroke-affected site. In vivo lentiviral gene delivery of GOT minimized lesion volume, whereas GOT knockdown worsened stroke outcomes. Thus, brain tissue GOT emerges as a novel target in managing stroke outcomes. This work demonstrates that correction of hypoxia during AIS can help clear extracellular neurotoxic Glu by enabling utilization of this amino acid as a metabolic fuel to support survival of the hypoglycemic brain tissue. Strategies to mitigate extracellular Glu-mediated neurodegeneration via blocking receptor-mediated excitotoxicity have failed in clinical trials. We introduce the concept that under hypoglycemic conditions extracellular Glu can be transformed from a neurotoxin to a survival factor by GOT, provided there is sufficient oxygen to sustain cellular respiration.     

Developing digital tissue phantoms for hyperspectral imaging of ischemic wounds

Hyperspectral imaging has the potential to achieve high spatial resolution and high functional sensitivity for non-invasive assessment of tissue oxygenation. However, clinical acceptance of hyperspectral imaging in ischemic wound assessment is hampered by its poor reproducibility, low accuracy, and misinterpreted biology. These limitations are partially caused by the lack of a traceable calibration standard. We proposed a digital tissue phantom (DTP) platform for quantitative calibration and performance evaluation of spectral wound imaging devices. The technical feasibility of such a DTP platform was demonstrated by both in vitro and in vivo experiments. The in vitro DTPs were developed based on a liquid blood phantom model. The in vivo DTPs were developed based on a porcine ischemic skin flap model. The DTPs were projected by a Hyperspectral Image Projector (HIP) with high fidelity. A wide-gap 2nd derivative oxygenation algorithm was developed to reconstruct tissue functional parameters from hyperspectral measurements. In this study, we have demonstrated not only the technical feasibility of using DTPs for quantitative calibration, evaluation, and optimization of spectral imaging devices but also its potential for ischemic wound assessment in clinical practice.     

Surgical Repair of Submitral Aneurysm: A Case Report

Aim: External, non‐restrictive, macro‐porous stents prevent neointima formation in porcine vein grafts and have been proposed as a therapeutic approach to the prevention of late vein graft failure. Since these stents are non‐biodegradable and therefore may elicit deleterious long‐term, inflammatory, infective and mechanical complications the effect of external macro‐porous biodegradable (polyglactin) stents on neointimal and medial thickening in porcine vein grafts was investigated. Methods: Bilateral vein saphenous vein‐carotid artery interposition grafting was performed in Large White pigs (22–36 kg, n = 6 ) with external placement of 8 mm diameter polyglactin stents on one side, the contralateral side acting as a control. One month after surgery, graft wall dimensions were measured on histological sections using computer‐aided planimetry and immunocytochemistry undertaken for selected parameters. Results: Polyglactin stents significantly reduced medial thickening compared to the All grafts were patent at explantation. Intimal thickness was significantly lower (p < 0.05) in the stented grafts (0.11 ± 0.01 mm) compared to the unstented controls (0.18 ± 0.01 mm) . Similarly, medial thickness was significantly lower (p < 0.05) in the stented grafts (0.24 ± 0.03 mm) compared to the unstented controls (0.43 ± 0.04 mm) mm. Grafts externally supported with polyglactin had a pronounced increase in inflammatory cells (in particular, giant cells) around the biodegradable stent compared to both unstented controls and previously studied Dacron stented grafts. The space between graft and stent had become organised into a neo‐adventitia with abundant microvessels which stained positively for VEGF and lectin (markers of micorvessels and endothelial cells). Conclusions: An over‐size biodegradable stent reduces medial thickening, a component of late vein graft failure in experimental grafts. If subsequent studies confirm the preservation of this beneficial effect when the stent biodegrades completely, this form of stent may have an advantage over permanent stent material in the clinical use of external stenting to prevent vein graft thickening and failure.     

Phase transformation in conformational polymorphs of nimesulide

Nimesulide is a nonsteroidal anti-inflammatory drug (NSAID) and a COX-2 inhibitor. The native crystal structure of nimesulide (or Form I) has been characterized in the literature by X-ray powder diffraction (XRPD) lines, whereas full three-dimensional coordinates are known for a second polymorph (Form II). A detailed structural characterization and phase stability of nimesulide polymorphs were carried out. Rod-like crystals of Form I (space group Pca2(1); number of symmetry-independent molecules, Z' = 2) were crystallized from EtOH concomitantly with Form II (C2/c, Z' = 1). These conformational polymorphs have different torsion angles at the phenoxy and sulfonamide groups. The crystal structures are stabilized by N-H · · · O hydrogen bonds and C-H · · · O, C-H · · · π interactions. Phase transition from the metastable Form (II) to the stable modification (I) was studied using differential scanning calorimetry, hot-stage microscopy, solid-state grinding, solvent-drop grinding, and slurry crystallization. The phase transition was monitored by infrared, Raman, and ss-nuclear magnetic resonance spectroscopy; and XRPD and single-crystal X-ray diffraction. The stable polymorph I was obtained in excess during solution crystallization, grinding, and slurry methods. Intrinsic dissolution and equilibrium solubility experiments showed that the metastable Form II dissolves much faster than the stable Form I.     

Neutrophil lymphocyte ratio: a reliable biomarker for diabetic nephropathy?

International Journal of Diabetes in Developing Countries - Inflammation plays a central role in pathogenesis of diabetic nephropathy (DN), a major cause of morbidity and mortality in type 2...