Knowledge, Attitude and Practice (KAP) study on COVID-19 among the general population of Nepal.

The COVID-19 pandemic has become one of the global health challenges in the current context. In Nepal, the first confirmed case was reported on 23 January 2020, and since then it has resulted in several negative impacts including economic disruption and deterioration of physical and mental health. In such a pandemic, it is indispensable to understand the knowledge and behavioral patterns of the general population regarding COVID-19. Therefore, our study aimed to assess the knowledge, attitude and practice on COVID-19, among the general population and its relationship with socio-demographic conditions. The questionnaire survey was conducted to collect data from eight districts of Nepal which included Kathmandu, Bhaktapur, Lalitpur, Morang, Sunsari, Rupandehi, Chitwan, and Kaski. Descriptive statistics, parametric and non-parametric statistical tests, and a logistic regression model were used for analysis. The study showed that 93.3% of respondents had knowledge of overall preventive practice whereas only 32% had knowledge of overall symptoms of COVID-19. Regarding attitude, only 14.3% believed that they will get rid of COVID-19 soon. The preventive practice was reduced after lockdown compared to that during lockdown. The respondents with white-collar occupations, high-income, and unmarried were good at KAP. Similarly, highly educated and those residing in urban areas had good knowledge and practice. The study findings will help in the development of targeted programs to improve the knowledge, attitude, practice of the general population on COVID-19, which is of paramount importance to deal with the existing pandemic and also such possible future waves of the pandemic.

Cancer immunotherapy by immune checkpoint blockade and its advanced application using bio-nanomaterials.

Cancer is the second leading cause of death worldwide. Traditional approaches, such as surgery, chemotherapy, and radiotherapy have been the main cancer therapeutic modalities in recent years. Cancer immunotherapy is a novel therapeutic modality that potentiates the immune responses of patients against malignancy. Immune checkpoint proteins expressed on T cells or tumor cells serve as a target for inhibiting T cell overactivation, maintaining the balance between self-reactivity and autoimmunity. Tumors essentially hijack the immune checkpoint pathway in order to survive and spread. Immune checkpoint inhibitors (ICIs) are being developed as a result to reactivate the anti-tumor immune response. Recent advances in nanotechnology have contributed to the development of successful, safe, and efficient anticancer drug systems based on nanoparticles. Nanoparticle-based cancer immunotherapy overcomes numerous challenges and offers novel strategies for improving conventional immunotherapies. The fundamental and physiochemical properties of nanoparticles depend on various cancer therapeutic strategies, such as chemotherapeutics, nucleic acid-based treatments, photothermal therapy, and photodynamic agents. The review discusses the use of nanoparticles as carriers for delivering immune checkpoint inhibitors and their efficacy in cancer combination therapy.

The Therapeutic Potential of Algal Nanoparticles: A Brief Review.

Recently, the green synthesis of metallic nanoparticles (NPs) has received tremendous attention as a simple approach. The green pathway of biogenic synthesis of metallic NPs through microbes may provide a sustainable and environmentally friendly protocol. Green technology is the most innovative technology for various biological activities and lacks toxic effects. Reports have shown the algae-mediated synthesis of metal NPs. Algae are widely used for biosynthesis as they grow fast; they produce biomass on average ten times that of plants and are easily utilized experimentally. In the future, the production of metal NPs by different microalgae and their biological activity can be explored in diverse areas such as catalysis, medical diagnosis, and anti-biofilm applications.

Dietary Nutrients and Prevention of Alzheimer's Disease.

Alzheimer's disease is an irrevocable, progressive brain disorder that gradually destroys memory and cognitive skills. One of the extensively studied methods of preventing Alzheimer's disease (AD) progression is by providing a nutritional diet. Several reports have shown that intake of nutritional elements as huperzine A, ursolic acid, vitamins etc., can directly influence pathogenesis of AD. Surprisingly, the occurrence of metabolic disorders due to an unhealthy diet has been known to be a major environmental cause of AD. It has been noted that AD severity can be controlled by supplementing dietary supplements containing huge amounts of health-promoting ingredients. These elements promote cell health, regeneration, and the anti-aging process that specifically interrupt the pathogenic pathways in AD development. Fortunately, incorporating changes in the nutritional content is inexpensive, easy, acceptable, safe, effective, and in most cases, free from major adverse events. Many nutritional phytoconstituents such as flavonoids, alkaloids, and terpenoids are still being evaluated in the hope of identifying a successful therapy for AD. This review discusses the therapeutical potential of several key nutrients that have been researched for treating AD treatment and the method of their neuroprotective intervention.

The Therapeutic Potential of the Anticancer Activity of Fucoidan: Current Advances and Hurdles.

Several types of cancers share cellular and molecular behaviors. Although many chemotherapy drugs have been designed to weaken the defenses of cancer cells, these drugs may also have cytotoxic effects on healthy tissues. Fucoidan, a sulfated fucose-based polysaccharide from brown algae, has gained much attention as an antitumor drug owing to its anticancer effects against multiple cancer types. Among the anticancer mechanisms of fucoidan are cell cycle arrest, apoptosis evocation, and stimulation of cytotoxic natural killer cells and macrophages. Fucoidan also protects against toxicity associated with chemotherapeutic drugs and radiation-induced damage. The synergistic effect of fucoidan with existing anticancer drugs has prompted researchers to explore its therapeutic potential. This review compiles the mechanisms through which fucoidan slows tumor growth, kills cancer cells, and interacts with cancer chemotherapy drugs. The obstacles involved in developing fucoidan as an anticancer agent are also discussed in this review.

Modifiable Risk Factors Associated with Alzheimer's Disease with Special Reference to Sleep Disturbance.

Sleep disorders have been shown to increase the risk of dementia. This particular aspect may affect the cognition of the patient, leading to behavioral disorders and depression. In early symptomatic Alzheimer's Disease (AD), Default Mode Network (DMN) disruption occurs and progresses along with the course of the disease. This review mainly focuses on the leading causes of AD along with management of conditions like insomnia, obstructive sleep apnea, night-time sleep duration, Circadian Rhythm Disorder (CRD), neuroendocrine alternation, and impaired sleep to prevent the use of drugs that can cause complications, especially falls or additional cognitive deficits. Moreover, this study highlights the identification of molecular mechanisms like the effect of impaired sleep on amyloid ß (Aß) and tau dynamics, impaired proteostasis, along with appropriate measures to treat few contributing factors that lead to insomnia in AD or Mild Cognitive Impairment (MCI).

Evidence for SARS-CoV-2 Spike Protein in the Urine of COVID-19 patients

SARS-CoV-2 infection has so far affected over 42 million people worldwide, causing over 1.1 million deaths. With the large majority of SARS-CoV-2 infected individuals being asymptomatic, major concerns have been raised about possible long-term consequences of the infection. We developed an antigen capture assay to detect SARS-CoV-2 spike protein in urine samples from COVID-19 patients whose diagnosis was confirmed by PCR from nasopharyngeal swabs (NP-PCR+). The study used a collection of 233 urine samples from 132 participants from Yale New Haven Hospital and the Childrens Hospital of Philadelphia obtained during the pandemic (106 NP-PCR+ and 26 NP-PCR-) as well as a collection of 20 urine samples from 20 individuals collected before the pandemic. Our analysis identified 23 out of 91 (25%) NP-PCR+ adult participants with SARS-CoV-2 spike S1 protein in urine (Ur-S+). Interestingly, although all NP-PCR+ children were Ur-S-, 1 NP-PCR-child was found to be positive for spike protein in urine. Of the 23 Ur-S+ adults, only 1 individual showed detectable viral RNA in urine. Our analysis further showed that 24% and 21% of NP-PCR+ adults have high levels of albumin and cystatin C in urine, respectively. Among individuals with albuminuria (>0.3 mg/mg of creatinine) statistical correlation could be found between albumin and spike protein in urine. Together, our data showe that 1 of 4 of SARS-CoV-2 infected individuals develop renal abnormalities such as albuminuria. Awareness about the long-term impact of these findings is warranted.

Exploring the Role of Gene Therapy for Neurological Disorders.

Gene therapy is one of the frontier fields of medical breakthroughs that poses as an effective solution to previously incurable diseases. The delivery of the corrective genetic material or a therapeutic gene into the cell restores the missing gene function and cures a plethora of diseases, incurable by the conventional medical approaches. This discovery holds the potential to treat many neurodegenerative disorders such as muscular atrophy, multiple sclerosis, Parkinson's disease (PD) and Alzheimer's disease (AD), among others. Gene therapy proves as a humane, cost-effective alternative to the exhaustive often arduous and timely impossible process of finding matched donors and extensive surgery. It also overcomes the shortcoming of conventional methods to cross the blood-brain barrier. However, the use of gene therapy is only possible after procuring the in-depth knowledge of the immuno-pathogenesis and molecular mechanism of the disease. The process of gene therapy can be broadly categorized into three main steps: elucidating the target gene, culling the appropriate vector, and determining the best mode of transfer; each step mandating pervasive research. This review aims to dissertate and summarize the role, various vectors and methods of delivery employed in gene therapy with special emphasis on therapy directed at the central nervous system (CNS) associated with neurodegenerative diseases.

Recent Advances in Nanotechnology: A Novel Therapeutic System for the Treatment of Alzheimer's Disease.

A amyloid-ß (Aß) plaque formation in the brain is known to be the root cause of Alzheimer's disease (AD), which affects the behavior, memory, and cognitive ability in humans. The brain starts undergoing changes several years before the actual appearance of the symptoms. Nanotechnology could prove to be an alternative strategy for treating the disease effectively. It encompasses the diagnosis as well as the therapeutic aspect using validated biomarkers and nano-based drug delivery systems, respectively. A nano-based therapy may provide an alternate strategy, wherein one targets the protofibrillar amyloid-ß (Aß) structures, and this is followed by their disaggregation as random coils. Conventional/routine drug therapies are inefficient in crossing the blood-brain barrier; however, this hurdle can be overcome with the aid of nanoparticles. The present review highlights the various challenges in the diagnosis and treatment of AD. Meticulous and collaborative research using nanotherapeutic systems could provide remarkable breakthroughs in the early-stage diagnosis and therapy of AD.

Convalescent plasma in the management of moderate COVID-19 in India: An open-label parallel-arm phase II multicentre randomized controlled trial (PLACID Trial)

ObjectivesConvalescent plasma (CP) as a passive source of neutralizing antibodies and immunomodulators is a century-old therapeutic option used for the management of viral diseases. We investigated its effectiveness for the treatment of COVID-19. DesignOpen-label, parallel-arm, phase II, multicentre, randomized controlled trial. SettingThirty-nine public and private hospitals across India. ParticipantsHospitalized, moderately ill confirmed COVID-19 patients (PaO2/FiO2: 200-300 or respiratory rate > 24/min and SpO2 [≤] 93% on room air). InterventionParticipants were randomized to either control (best standard of care (BSC)) or intervention (CP + BSC) arm. Two doses of 200 mL CP was transfused 24 hours apart in the intervention arm. Main Outcome MeasureComposite of progression to severe disease (PaO2/FiO2< 100) or all-cause mortality at 28 days post-enrolment. ResultsBetween 22nd April to 14th July 2020, 464 participants were enrolled; 235 and 229 in intervention and control arm, respectively. Composite primary outcome was achieved in 44 (18.7%) participants in the intervention arm and 41 (17.9%) in the control arm [aOR: 1.09; 95% CI: 0.67, 1.77]. Mortality was documented in 34 (13.6%) and 31 (14.6%) participants in intervention and control arm, respectively [aOR) 1.06 95% CI: -0.61 to 1.83]. InterpretationCP was not associated with reduction in mortality or progression to severe COVID-19. This trial has high generalizability and approximates real-life setting of CP therapy in settings with limited laboratory capacity. A priori measurement of neutralizing antibody titres in donors and participants may further clarify the role of CP in management of COVID-19. Trial registrationThe trial was registered with Clinical Trial Registry of India (CTRI); CTRI/2020/04/024775.

Therapeutic Advancements in the Management of Diabetes Mellitus with Special Reference to Nanotechnology.

For improvisation of diabetic's quality of life, nanotechnology is facilitating the development of advanced glucose sensors as well as efficient insulin delivery systems. Our prime focus of the review is to highlight the advancement in diabetic research with special reference to nanotechnology at its interface. Recent studies are more focused on enhancing sensitivity, accuracy, and response by employing metal as well as nanoparticles based glucose sensors. Moreover, the review focuses on nanoscale based approaches i.e. closed-loop insulin delivery systems, which detect any fluctuation in blood glucose levels and allow controlled release of a drug, thus are also called self-regulating insulin release system. Additionally, this review summarizes the role of nanotechnology in the diagnosis and treatment of diabetic complications through little advancement in the existing techniques. To improve health, as well as the quality of life in diabetic's new sensing systems for blood glucose level evaluation and controlled administration of drugs through efficient drug delivery systems should be explored.

Continuous B scan ultrasound guided post-traumatic sub-periosteal orbital hematoma drainage: An advantage over routine needle drainage procedure / 世界急诊医学杂志（英文）

@#Traumatic orbital haemorrhage is an unfortunate complication with potential vision-threatening consequences.[1-3] The collection of blood can occur anywhere along the potential free orbital spaces,[4] but the subperiosteal collection of the blood is an important clinical variant where careful and timely intervention can give commendable rewards to the surgeon as well as to the patient.[1,2] Subperiosteal hematoma could be traumatic or non-traumatic, in turns, the non-traumatic cases may be due to bleeding tendency as in cases of leukaemia, blood dyscrasia and haemophilia or could be due to vascular malformation, venous congestion, infection, inflammation and neoplastic and non- neoplastic causes.[4] Here in this report, we elaborate the advantage of continuous ultrasound-guided needle drainage of the post-traumatic subperiosteal hematoma to enhance the clinical accuracy and to avoid the untoward complications.

Biofabrication of Copper Nanoparticles: A Next-generation Antibacterial Agent Against Wound-associated Pathogens.

OBJECTIVES: Impaired wound healing is a major complication. A few factors such as blood glucose level, poor circulation, immune system deficiency, and infection are the root causes of impaired wound healing. The aim of the present study was to bio-synthesize copper nanoparticles with potential antibacterial activity against wound-associated pathogens. MATERIALS AND METHODS: Copper nanoparticles were fabricated using the sol-gel method with the mixing of Syzigium cumini leaf extract in metal salt solution. The particles were then later characterized using UV spectroscopy, SEM, TEM, FTIR, and XRD, and evaluated for their antibacterial activity and its MIC against four wound-associated pathogens. RESULTS: The results obtained from TEM, SEM, and XRD characterization showed that the particle size was below 100 nm and of spherical shape. FTIR analysis showed the possibility of various biomolecules, which have a role in capping and stabilizing copper nanoparticles. The particles synthesized showed antibacterial activity against four wound-associated pathogens (P. mirabilis, S. saprophyticus, S. pyogenes, and P. aeruginosa). CONCLUSION: The biosynthesized copper nanoparticles showed potent antimicrobial activity, thus the antibacterial activity of the synthesized copper nanoparticles could be used in several biomedical applications. Additionally, they can be exploited as a better therapeutic agent for treating infection seen in impaired diabetic wounds. The particles synthesized by the biological route are eco-friendly, less toxic, feasible, and cost effective.