The COVID‐19 Pandemic Not Only Poses Challenges, but Also Opens Opportunities for Sustainable Transformation

The COVID-19 pandemic has impacted social, economic, and environmental systems worldwide, slowing down and reversing the progress made in achieving the Sustainable Development Goals (SDGs). SDGs belong to the 2030 Agenda to transform our world by tackling humankind's challenges to ensure well-being, economic prosperity, and environmental protection. We explore the potential impacts of the pandemic on SDGs for Nepal. We followed a knowledge co-creation process with experts from various professional backgrounds, involving five steps: online survey, online workshop, assessment of expert's opinions, review and validation, and revision and synthesis. The pandemic has negatively impacted most SDGs in the short term. Particularly, the targets of SDG 1, 4, 5, 8, 9, 10, 11, and 13 have and will continue to have weakly to moderately restricting impacts. However, a few targets of SDG 2, 3, 6, and 11 could also have weakly promoting impacts. The negative impacts have resulted from impeding factors linked to the pandemic. Many of the negative impacts may subside in the medium and long terms. The key five impeding factors are lockdowns, underemployment and unemployment, closure of institutions and facilities, diluted focus and funds for non-COVID-19-related issues, and anticipated reduction in support from development partners. The pandemic has also opened a window of opportunity for sustainable transformation, which is short-lived and narrow. These opportunities are lessons learned for planning and action, socio-economic recovery plan, use of information and communication technologies and the digital economy, reverse migration and “brain gain,” and local governments' exercising authorities

Gene Therapy Using Adeno-Associated Virus Vectors

Summary: The unique life cycle of adeno-associated virus (AAV) and its ability to infect both nondividing and dividing cells with persistent expression have made it an attractive vector. An additional attractive feature of the wild-type virus is the lack of apparent pathogenicity. Gene transfer studies using AAV have shown significant progress at the level of animal models; clinical trials have been noteworthy with respect to the safety of AAV vectors. No proven efficacy has been observed, although in some instances, there have been promising observations. In this review, topics in AAV biology are supplemented with a section on AAV clinical trials with emphasis on the need for a deeper understanding of AAV biology and the development of efficient AAV vectors. In addition, several novel approaches and recent findings that promise to expand AAV's utility are discussed, especially in the context of combining gene therapy ex vivo with new advances in stem or progenitor cell biology

Adeno-Associated Virus Site-Specific Integration Is Mediated by Proteins of the Nonhomologous End-Joining Pathway▿

Adeno-associated virus type 2 (AAV 2) is the only eukaryotic virus capable of site-specific integration; the target site is at chromosome 19q13.4, a site termed AAVS1. The biology of AAV latency has been extensively studied in cell culture, yet the precise mechanism and the required cellular factors are not known. In this study, we assessed the relative frequencies of stable site-specific integration by characterization of cell clones containing integrated AAV vectors. By this assay, two proteins involved in nonhomologous end joining (NHEJ), DNAPKcs and ligase IV, exhibit differential effects on AAV site-specific integration. DNAPKcs is not required; its presence increases the frequency of junction formation indicative of site-specific integration, but seems to reduce the ratio of site-specific integration to random integration (i.e., the latter is even more enhanced). In contrast, site-specific integration is significantly reduced relative to random integration in cells deficient in ligase IV expression. Furthermore, we show that single-stranded AAV vectors are better substrates for site-specific integration than are self-complementary AAV vectors; the absence of DNAPKcs did not affect the targeted integration of these double-stranded AAV vectors. Together, these data suggest that NHEJ proteins participate in site-specific integration, and indicate a role for the single-stranded form of AAV DNA in targeted integration

Novel Brentuximab Vedotin Combination Therapies Show Promising Activity in Highly Refractory CD30+ Non-Hodgkin Lymphoma: A Case Series and Review of the Literature

Non-Hodgkin lymphomas (NHLs) are a heterogeneous group of hematologic malignancies which typically respond to standard first-line chemoimmunotherapy regimens. Unfortunately, patients with refractory NHL face a poor prognosis and represent an unmet need for improved therapeutics. We present two cases of refractory CD30+ NHL who responded to novel brentuximab vedotin- (BV-) based regimens. The first is a patient with stage IV anaplastic large cell lymphoma (ALCL) with cranial nerve involvement who failed front-line treatment with cyclophosphamide, doxorubicin, vincristine, etoposide, and prednisone (CHOEP) and second line cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with high-dose methotrexate (MTX), and cytarabine (hyperCVAD) with intrathecal- (IT-) MTX and IT-cytarabine, but responded when BV was substituted for vincristine (hyperCBAD). The second patient was a man with stage IV diffuse large B-cell lymphoma (DLBCL) with leptomeningeal involvement whose disease progressed during first-line rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) and progressed despite salvage therapy with rituximab, dexamethasone, cytarabine, and cisplatin (R-DHAP) in whom addition of BV to topotecan resulted in a significant response. This report describes the first successful salvage treatments of highly aggressive, double refractory CD30+ NHL using two unreported BV-based chemoimmunotherapy regimens. Both regimens appear effective and have manageable toxicities. Further clinical trials assessing novel BV combinations are warranted

Amoebic Liver Abscess: A Complete Overview in Tertiary Care Centre

Introduction: Amoebiasis is defined as human infection with protozoan parasite, Entamoeba histolytica regardless of the clinical outcome. It commonly resides in large intestine but can invade to other organs. Amoebic Liver Abscess (ALA) is the most common complication of invasive amoebiasis. Aim: To study various aspects of ALA like demographic profiles, clinical features, radiological and laboratory findings and treatment. Materials and Methods: A cross-sectional study was performed in the Department of Microbiology, Maulana Azad Medical College, New Delhi, India, from October 2012 to April 2014. Pus, blood and stool samples were taken from each patient after taking informed consent and examined for trophozoite by microscopy, IgG antibody and antigen of Entamoeba histolytica by ELISA respectively. The results were presented as mean for quantitative variables and percentages for qualitative data. Calculations were done using Microsoft Excel software. Results: Total 65 patients with age more than 18 year were enrolled in the study out of which 39 cases (60%) were diagnosed as ALA. The age ranged from 18 to 90 years (mean age 37.1 year). Male patients were dominated over female. About 74.3% patients were addicted to alcohol. Most patients had acute presentation. Pain in abdomen and fever were the most common symptoms observed (97.4% and 94.8% respectively). The right lobe was involved in 76.9% cases. Solitary abscess was found in 82.0% cases out of which 64.1% were in right lobe. Volume of abscess ranged between 70 cc and as much as 1200 cc. Volume less than 300 cc was seen in 17 cases (43.5%) and more than 300 cc was seen in 22 cases (56.5%). Pleural effusion and intra peritoneal rupture were the two complications (28.2% and 10.2%) found in this study. All patients were treated successfully with or without help of percutaneous intervention. Conclusion: ALA presents itself through various non specific symptoms and signs. Confirmation of diagnosis is made possible with the help of radiological and microbiological methods. Prompt diagnosis and treatment can markedly reduce the complication and mortality