Exploring state-of-the-art advances in targeted nanomedicines for managing acute and chronic inflammatory lung diseases

Diagnosis and treatment of lung diseases pose serious challenges. Currently, diagnostic as well as therapeutic methods show poor efficacy toward drug-resistant bacterial infections, while chemotherapy causes toxicity and nonspecific delivery of drugs. Advanced treatment methods that cure lung-related diseases, by enabling drug bioavailability via nasal passages during mucosal formation, which interferes with drug penetration to targeted sites, are in demand. Nanotechnology confers several advantages. Currently, different nanoparticles, or their combinations, are being used to enhance targeted drug delivery. Nanomedicine, a combination of nanoparticles and therapeutic agents, that delivers drugs to targeted sites increases the bioavailability of drugs at these sites. Thus, nanotechnology is superior to conventional chemotherapeutic strategies. Here, the authors review the latest advancements in nanomedicine-based drug-delivery methods for managing acute and chronic inflammatory lung diseases

Strengthening self-regulation and reducing poverty to prevent adolescent depression and anxiety: rationale, approach and methods of the ALIVE interdisciplinary research collaboration in Colombia, Nepal and South Africa

Aims Depression and anxiety are the leading contributors to the global burden of disease among young people, accounting for over a third (34.8%) of years lived with disability. Yet there is limited evidence for interventions that prevent adolescent depression and anxiety in low- and middle-income countries (LMICs), where 90% of adolescents live. This article introduces the ‘Improving Adolescent mentaL health by reducing the Impact of poVErty (ALIVE)’ study, its conceptual framework, objectives, methods and expected outcomes. The aim of the ALIVE study is to develop and pilot-test an intervention that combines poverty reduction with strengthening self-regulation to prevent depression and anxiety among adolescents living in urban poverty in Colombia, Nepal and South Africa. Methods This aim will be achieved by addressing four objectives: (1) develop a conceptual framework that identifies the causal mechanisms linking poverty, self-regulation and depression and anxiety; (2) develop a multi-component selective prevention intervention targeting self-regulation and poverty among adolescents at high risk of developing depression or anxiety; (3) adapt and validate instruments to measure incidence of depression and anxiety, mediators and implementation parameters of the prevention intervention; and (4) undertake a four-arm pilot cluster randomised controlled trial to assess the feasibility, acceptability and cost of the selective prevention intervention in the three study sites. Results The contributions of this study include the active engagement and participation of adolescents in the research process; a focus on the causal mechanisms of the intervention; building an evidence base for prevention interventions in LMICs; and the use of an interdisciplinary approach. Conclusions By developing and evaluating an intervention that addresses multidimensional poverty and self-regulation, ALIVE can make contributions to evidence on the integration of mental health into broader development policy and practice

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Single stage substitution urethroplasty using buccal mucosa graft in management of stricture urethra

Buccal mucosa graft and the Berbaglis technique are recent development in treatment of urethral stricture. We report results of 14 patients who were managed by single stage substitution urethroplasty using buccal mucosa graft. Patients and Methods: From July 2002 to June 2004, 14 patients of mean age 27.02yrs (range 20 to 54) underwent dorsal onlay graft urethroplasty (Simple onlay in 12 patients and augmented type in 2 patients). All patients were evaluated preoperatively and postoperatively with uroflowmetry, retrograde and voiding urethrogram. Results: Overall success rate was 85.71% and only 2 patients had restricture. Out of 14 patients 3 patients had leak at repair site which was managed conservatively. Conclusion: Dorsal onlay graft urethroplasty is a versatile technique. The intrinsic properties of buccal mucosa also make it a better substitute for urethroplasty

Deciphering the dilemma of parametric and nonparametric tests

The potential source of complexity while analyzing the data is to choose on whether the data collected could be analyzed properly by the application of parametric tests or nonparametric tests. This concern cannot be underrated as there are certain assumptions which should be fulfilled before analyzing the data by applying either of the two types of tests. This article describes in detail the difference between parametric and nonparametric tests, when to apply which and the advantages of using one over the other

Analyzing agreement patterns of intraoperative central nervous system lesion reporting according to type and grade

Background: Neuropathology centers are expected to offer a prompt and accurate intraoperative diagnosis regarding tumor/lesion type and grade on fresh unfixed tissue. Level of diagnostic accuracy according to type and grade and also, the experience at a new center has not been reported before. Aims: The aim of this study is to review the agreement patterns according to tumor/lesion type and grade between intraoperative and final histopathologic diagnosis in central nervous system (CNS) lesion samples received by a newly established neuropathology center at a tertiary care neuropsychiatric hospital. Materials and Methods: Agreement between intraoperative and final histopathologic diagnosis was classified as: (I) Grade in agreement but type not in agreement; (II) grade not in agreement but type in agreement; (III) grade and type both not in agreement; (IV) grade and type both in agreement. Statistical Analysis: Confidence interval (CI) of agreements was calculated for various categories of neoplastic as well as non-neoplastic lesions. CI was also calculated for groups where n × p and n × (1 − p) were more than 5, i.e., fulfilled the requirement of the central limit theorem. Results: On retrospective analysis of 333 cases, 284 (85.3%) cases were categorized as neoplastic while 49 (14.7%) cases were categorized as non-neoplastic. Among the neoplastic lesions agreement was seen in 237 (83.5%) cases while 47 (16.5%) cases showed disagreement. Similarly in non-neoplastic category; 46 (93.9%) cases showed agreement while 3 (6.15%) cases showed disagreement. Of the non-neoplastic lesions, one case fell into the agreement category I, 2 in category III and 46 in IV. Among neoplastic lesions, there were 21 cases in agreement category I, 17 in II, 9 in III and 237 in IV. On analyzing the accuracy of intraoperative reporting according to tumor type, the break up was: - Astrocytic: 2 (I), 16 (II), 2 (III), 86 (IV); oligodendroglial: 8 (I), 1 (II); ependymal: 2 (III), 6 (IV); embryonal: 23 (IV); cranial and spinal nerve tumors: 2 (II), 21 (IV); choroid plexus tumors: 4 (IV); meningeal tumors: 3 (I), 1 (III), 49 (IV); metastatic tumors: 3 (I), 17 (IV); cysts (tumor-like conditions): 14 (IV); neuronal and mixed neuronal glial tumors: 1 (III); malignant lymphoma: 1 (III); sellar tumors: 17 (IV); and mixed gliomas: 5 (I). Conclusions: This study identifies problem areas of CNS intraoperative reporting, in a new center, with reference to tumor typing and grading. It may forewarn upcoming centers of neuropathology about the potential problem areas of intraoperative reporting

Spinal actinomycosis: A rare disease

Actinomycosis is an indolent, slowly progressive infection caused by Actinomyces species. Of human actinomycosis, the spinal form is rare and actinomycosis-related spinal neurological deficit is uncommon. We report two cases with cervical and dorsal actinomycosis and one of them with spinal neurological deficit

Scrolling Characteristics of Pre-Descemet Endothelial Keratoplasty Tissue: An Ex Vivo Study

PurposeTo evaluate the scrolling propensity of pre-Descemet endothelial keratoplasty (PDEK) tissue and to compare it with each component of the PDEK tissue, namely the pre-Descemet layer (Dua's layer [PDL]) and the Descemet membrane (DM).DesignExperimental laboratory investigation.MethodsFourteen human donor sclerocorneal discs in which a type 1 big bubble was obtained by stromal injection of air were studied. The wall of the type 1 big bubble was excised and its grade of scrolling noted. The components of the wall (ie, the DM and PDL) were then separated and the scrolling of each was individually graded. Statistical comparison of the grade of scrolling of each layer and correlation with age was carried out; 25-?m slices of anterior and posterior stroma obtained with the femtosecond laser from 4 control samples were used for comparison. The main outcome measure was the grade of scrolling of PDEK tissue in comparison with PDL and DM.ResultsMean donor age was 67 years. The mean grade of the scroll formed by PDEK tissue was1.6 compared to 0.64 for PDL alone and 3.6 for DM alone. The difference was statistically significant. No correlation between donor age and degree of scrolling for any of the tissues tested was found.ConclusionPDEK tissue scrolls less than DM. PDL scrolls the least. This demonstrates that PDL tissue splints the DM and reduces its scrolling in PDEK. This feature has relevance to tissue preparation, handling, and unscrolling in the eye during endothelial keratoplasty