The Double Burden of COVID-19 and Dengue in Nepal: The challenges ahead.

Coronavirus disease 2019 (COVID-19) pandemic has caused significant impact on the health care system. As a consequence, diagnosis and treatment of vector borne diseases including dengue has been equally affected. Nepal is no exception to this, where COVID-19 cases is exponentially increased and all resources are concentrated on its prevention, control and management. Dengue, one of the major vector-borne diseases in Nepal, is apparently overlooked despite approaching the peak season of the disease. The aim of this paper is to describe the double burden of COVID-19 and dengue in Nepal, particularly highlighting the co-circulation and possible coinfections. This has posed higher risk of increased severity, more severe cases and deaths in Nepal. Moreover, potential misdiagnosis of these viral diseases may lead to delayed or, inappropriate treatment and poor allocation of resources.

MMP9-sensitive polymers mediate environmentally-responsive bivalirudin release and thrombin inhibition.

MMP9-responsive bivalirudin-HPMA copolymers were synthesized for direct, local administration in rat spinal cord contusion injury models. Polymer-conjugated bivalirudin peptides maintained activity while demonstrating enzyme-mediated release upon MMP9 exposure and prolonged release from hyaluronic acid/methylcellulose (HAMC) hydrogels compared to free bivalirudin peptide. Localized administration of bivalirudin copolymers in vivo at the site of rat spinal cord injury decreased cellular proliferation and astrogliosis, suggesting the bivalirudin copolymer and HAMC hydrogel system are a promising therapeutic intervention for reducing immediate inflammatory responses and long term scarring.

Understanding the burden of disease in Nepal: a call for local evidence.

The burden of disease, most commonly expressed in terms of Disability-Adjusted Life Years, has become a crucial component in decision making processes within the health sector. In Nepal, however, burden of disease estimates are scarce and lack representativeness. To improve our understanding of the burden of disease in Nepal and thereby increase the efficiency of health policies, there is an urgent need to strengthen the local evidence base. All relevant stakeholders should therefore collaborate to generate new data, improve existing data generation mechanisms, make generated data available, and optimize the use of available data.

Comparative study of microscopy and polymerase chain reaction for the diagnosis of suspected visceral leishmaniasis patients in Nepal.

BACKGROUND: Visceral leishmaniasis is potentially fatal protozoan diseases caused by Leishmania donovani. Nepal is an endemic region in which visceral leishmaniasis causes a major public health problem in the lowland areas that border the endemic areas of Bihar state in India. Accurate diagnosis to inform treatment is a first step in achieving the goal of visceral leishmaniasis elimination from South East Asian regions by 2020. OBJECTIVE: The objective of the present study was to compare between the Microcopy and polymerase chain reaction for diagnosis of visceral leishmaniasis. METHODS: In the present study, 236 bone marrow aspirations were collected from suspected visceral leishmaniasis patients in Janakpur Zonal Hospital, Dhanusa district, Terai region of Nepal in between 2003-2007. We evaluated bone marrow samples by microscopic examination with subsequent testing of the same sample by polymerase chain reaction and sequence analysis. RESULTS: Giemsa's solution stained bone marrow slides stored for over five years were used for polymerase chain reaction amplification. The result showed that 71% were polymerase chain reaction positive and 56% were microscopic positive. Out of 104 microscopic negative bone marrow samples, 15% of samples were positive by polymerase chain reaction. CONCLUSION: Polymerase chain reaction could make a very good option for diagnosis by using less or non-invasive material from visceral leishmaniasis patients in endemic areas of Nepal.

Relapse of kala-azar after use of multiple drugs: a case report and brief review of literature.

We present a case of kala-azar infection that recurred in a patient after completion of the standard treatment course of miltefosine, amphotericin B-deoxycholate (short course), and amphotericin B lipid formulations. The patient was cured after continuous amphotericin B-deoxycholate administration for 4 weeks. This is a unique case of relapse following the use of three important drugs. Although amphotericin B-deoxycholate is a second line drug in Nepal, it has shown a satisfactory clinical response with continuous treatment for 4 weeks. Therefore, an extended course of amphotericin B-deoxycholate may be beneficial in patients with resistance to the standard short course and other anti-leishmania drugs.

Human rotavirus associated diarrhea and strain diversity in Nepal.

Two new rotavirus vaccines were recently introduced to the market and have shown a tremendous impact in reducing severe diarrhea due to rotavirus in children. Diarrheal disease is a common cause of morbidity and mortality among Nepalese children. In anticipation of a rotavirus vaccine in Nepal, we systematically reviewed published articles on rotavirus infection in Nepal. Literatures were searched in health related national and international databases. Fifteen rotavirus related articles between 1978 and 2010 were identified. Of these, information from five articles were extracted and analyzed in the present study. Of 3671 participants, 864 were positive for rotavirus infection by ELISA. The prevalence ofrotavirus infection ranged from 12 to 39%. G1P[8] (25%) was the most frequent combined G and P genotype, followed by G12P[6] (23%) and G2P[4] (16%) between 2003 and 2007. Nearly 9% of analyzed rotavirus positive samples (G and P genotype) were non-typable. The data demonstrated that rotavirus is the most identifiable cause of severe diarrhea in children less than 5 years old in Nepal. The wide variety of rotavirus strains circulating in Nepal; underscore the need for continued surveillance. This will be the key to understanding the epidemiological characteristics of rotavirus disease and the impact of vaccination after introduction.

Dengue: an emerging disease in Nepal.

Dengue is an acute infectious disease caused by dengue viruses and transmitted by the Aedes species of mosquito. The rapid global spread of the dengue virus into new areas has begun to attract more research attention. A series of dengue fever outbreaks in several districts of Nepal has been recently observed. The evidence of all four serotypes (DEN - 1 - 4) could be a consequence of a sudden resurgence of a more severe dengue disease in Nepal. Health care providers need to become familiar with the disease to prevent or control the possibility of future outbreaks. The clinical features, diagnosis, treatment, epidemiological patterns and challenges of dengue virus infection in Nepal will be discussed here.

Trends of rotavirus in Nepal.

BACKGROUND: Rotavirus gastroenteritis is the major cause of morbidity and mortality in infants and young children worldwide. Safe and effective rotavirus vaccine is needed to have significant impact on severe rotavirus gastroenteritis. Currently, two live oral rotavirus vaccines have been licensed in many countries. Knowledge on distribution of human rotavirus of G and P types are essential before rotavirus vaccines are introduced in the target populations. OBJECTIVE: To observe the trends of rotavirus strains in children below five years of age, during the years, 2003-2005 in Nepal. METHODS: Stool specimen collected from children with acute diarrhea who were referred to observation unit or hospitalized in Kanti Children Hospital between 2003 and 2005 were examined. Meteorological data was obtained from Ministry of Environment, Nepal to examine the possibility on the impact of weather on rotavirus infection. RESULTS: Of 1250 stool specimens, 271(22%) were positive for rotavirus by Rotaclone ELISA. G1 was the most common serotype in the first year of study, and G2 in the following year. G12 serotype emerged and remained predominant in two consecutive years. In addition, G9 and G3 emerged in the second year of the study. Children less than three years of age were commonly affected. The records reveal that rotavirus infection is related to the climate, and is commonly seen in the dry season, peaking in January. CONCLUSIONS: Continued surveillance of different regions is needed to monitor the trend of rotavirus strains and to establish rotavirus disease burden, which will help policy makers to make a decision in introducing rotavirus vaccine in Nepal.

Multilayer limb quasi-static electromagnetic modeling with experiments for Galvanic coupling type IBC.

Intra-body communication (IBC) is a new, emerging, short-range and human body based communication methodology. It is a technique to network various devices on human body, by utilizing the conducting properties of human tissues. For currently fast developed Body area network(BAN)/Body sensor network(BSN), IBC is believed to have advantages in power consumption, electromagnetic radiation, interference from external electromagnetic noise, security, and restriction in spectrum resource. In this article, the authors propose an improved mathematical model, which includes both electrical properties and proportion of human tissues, for IBC on a human limb. By solving the mathematical model analytically on four-layer system (skin, fat, muscle, and bone) and conducting in-vivo experiment, a comparison has been conducted.

Niacin: from mechanisms of action to therapeutic uses.

Niacin has broad spectrum lipid modifying and anti-atherosclerotic properties. It is the most effective medication available for raising raise high density lipoprotein (HDL) levels. Despite statin therapy there remains a considerable residual cardiovascular risk attributed to low HDL levels. Currently, statins decrease cardiovascular events and death by about 25-40%. Trials with surrogate endpoints have shown a decrease in endpoints by 60-90% when a combination of statin and niacin has been used. There is a growing interest in niacin in combination therapy to fill the treatment gap by modifying lipid parameters other than low density lipoprotein cholesterol. This review addresses the role of niacin in comprehensive lipid management with an emphasis on its mechanism of action, formulations, side effects, evidence from clinical trials and also focuses on practical issues related to niacin therapy.

Rotavirus infection: an unrecognised disease in Nepal.

Rotavirus is the most common cause of acute infectious gastroenteritis in young children and is associated with substantial morbidity and mortality worldwide, mostly in developing countries. The global rotavirus disease burden has prompted study on their basic research, molecular epidemiology and vaccine development. Little is known about rotavirus infection among health professionals in Nepal. This article summarises basic and clinical features, treatment and prevention, epidemiological pattern, challenges and recommendations of human rotavirus infections in Nepal.

Modeling for intra-body communication with bone effect.

Intra-body communication (IBC) is a new, different "wireless" communication technique based on the human tissue. This short range "wireless" communication technology provides an alternative solution to wearable sensors, home health system, telemedicine and implanted devices. The development of the IBC enables the possibilities of providing less complexity and convenient communication methodologies for these devices. By regarding human tissue as communication channel, IBC making use of the conductivities properties of human tissue to send electrical signal from transmitter to receiver. In this paper, the authors proposed a new mathematical model for galvanic coupling type IBC based on a human limb. Starting from the electromagnetic theory, the authors treat human tissue as volume conductor, which is in analogous with the bioelectric phenomena analysis. In order to explain the mechanism of galvanic coupling type technique of IBC, applying the quasi-static approximation, the governing equation can be reduced to Laplace Equation. Finally, the analytical model is evaluated with on-body measurement for testing its performance. The comparison result shows that the developed mathematical model can provide good approximation for galvanic coupling type IBC on human limb under low operating frequencies.

Simple electrical model and initial experiments for intra-body communications.

Intra-Body Communication(IBC) is a short range "wireless" communication technique appeared in recent years. This technique relies on the conductive property of human tissue to transmit the electric signal among human body. This is beneficial for devices networking and sensors among human body, and especially suitable for wearable sensors, telemedicine system and home health care system as in general the data rates of physiologic parameters are low. In this article, galvanic coupling type IBC application on human limb was investigated in both its mathematical model and related experiments. The experimental results showed that the proposed mathematical model was capable in describing the galvanic coupling type IBC under low frequency. Additionally, the calculated result and experimental result also indicated that the electric signal induced by the transmitters of IBC can penetrate deep into human muscle and thus, provide an evident that IBC is capable of acting as networking technique for implantable devices.

Peptide-modified vectors for nucleic acid delivery to neurons.

Neuron-targeted nucleic acid delivery systems are important technologies for realizing the potential of gene therapy for nervous system disorders. However, neurons are difficult cells to transfect using non-viral vectors due in part to the specific and unique delivery challenges present in these cells. We have investigated several bioactive peptides for their ability to assist in overcoming delivery barriers in mammalian cells. We summarize here our recent progress in developing and applying peptide-modified polycations for nucleic acid delivery. In addition, we present data demonstrating the potential of using multicomponent, peptide-modified polycations for nucleic acid delivery to neurons.

Pregnancy outcomes of women with pruritus, normal bile salts and liver enzymes: a case control study.

BACKGROUND: Obstetric cholestasis (OC) is associated with increased maternal and perinatal complications. Nevertheless, data on pregnancy outcomes of women who experience pruritus on a transient basis, but have normal bile salts and liver function tests (LFT) is scarce. METHODS: The maternal and fetal outcomes of 144 women with pruritus but normal bile salts and LFTs were compared with the next delivered patient without itch who matched for age, ethnicity and parity. RESULTS: The study and control groups had similar mean gestational ages at delivery and birth weights (p>0.05, t test). However, women with pruritus were more likely to have meconium-stained liqor, abnormal intrapartum cardiotocography and postpartum hemorrhage (PPH) (p<0.05, Fisher's exact test). There appears to be a trend towards a higher rate of instrumental delivery (p=0.07) in the study compared to the control group, although this did not reach statistical significance. CONCLUSION: This study suggests that women who have transient pruritus with normal bile salts and liver biochemistry appear to have higher intrapartum and postpartum complications and require increased vigilance. In order to evaluate this finding, further prospective studies will be required.

Periodic rewetting enhances the viability of chondrocytes in human articular cartilage exposed to air.

Desiccation of articular cartilage during surgery is often unavoidable and may result in the death of chondrocytes, with subsequent joint degeneration. This study was undertaken to determine the extent of chondrocyte death caused by exposure to air and to ascertain whether regular rewetting of cartilage could decrease cell death. Macroscopically normal human cartilage was exposed to air for 0, 30, 60 or 120 minutes. Selected samples were wetted in lactated Ringer's solution for ten seconds every ten or 20 minutes. The viability of chondrocytes was measured after three days by Live/Dead staining. Chondrocyte death correlated with the length of exposure to air and the depth of the cartilage. Drying for 120 minutes caused extensive cell death mainly in the superficial 500 microm of cartilage. Rewetting every ten or 20 minutes significantly decreased cell death. The superficial zone is most susceptible to desiccation. Loss of superficial chondrocytes likely decreases the production of essential lubricating glycoproteins and contributes to subsequent degeneration. Frequent wetting of cartilage during arthrotomy is therefore essential.

Self-assembling nucleic acid delivery vehicles via linear, water-soluble, cyclodextrin-containing polymers.

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure and gene delivery are illustrated, and the roles of the cyclodextrin moieties for minimizing toxicity and forming inclusion complexes in the self-assembly processes are highlighted. This vehicle is the first example of a polymer-based gene delivery system formed entirely by self-assembly.

Transforming growth factor-beta administration modifies cyclosporine A-induced bone loss.

Cyclosporine A (CsA), a potent immunosuppressant used in transplantation, induces increased formation with excess resorption in the rat with resultant osteopenia. These findings are confirmed in the human model. Transforming growth factor-beta (TGF-beta) is reported to be involved in the coupling of bone formation with resorption and in vivo and in vitro stimulates osteoblasts, and in vitro inhibits osteoclasts. CsA stimulates secretion of TGF-beta1 in humans, which, while improving immunosuppression, may also contribute to renal toxicity. This study was performed determine whether exogenously administered TGF-beta would modify the bone effects of CsA. Male Sprague-Dawley rats, 6 months of age, were randomized to receive: TGF-beta and CsA vehicle (group A); TGF-beta 5 microg/kg three times per week and CsA vehicle (group B); TGF-beta vehicle and CsA 10 mg/kg (group C); or TGF-beta 5 microg/kg three times per week and CsA 10 mg/kg (group D). These were compared with control over 28 days. CsA, but not TGF-beta, increased serum 1,25(OH)(2)D levels throughout the study. CsA increased osteocalcin (BGP), but TGF-beta negated this effect. Histomorphometry confirmed the known effects of CsA, whereas TGF-beta alone had no effect. However, in combination, TGF-beta blocked CsA's effect and increased osteoblast recruitment and activity, as reflected by increased percent mineralizing surface, percent osteoid perimeter, bone formation rate (bone volume referent), and activation frequency. Thus, it appears as if TGF-beta administration may have potential in modulating the deleterious bone effects of CsA.

Decreased bone anabolic effect of basic fibroblast growth factor at fatty marrow sites in ovariectomized rats.

The purpose of the study was to compare the bone anabolic effects of basic fibroblast growth factor (bFGF) at hematopoietic (red) and fatty (yellow) marrow sites in ovariectomized (ovx) rats. Female Sprague Dawley rats were subjected to ovariectomy or sham surgery at 3 months of age and maintained untreated for 2 months after surgery. Three groups of ovx rats were then injected intravenously with bFGF for 14 days at a dose of 200 microg/kg body weight. One group of bFGF-treated OVX rats was killed at the end of the treatment period, whereas the other two groups were killed at 7 or 14 days after withdrawal of bFGF treatment. Another group of ovx rats and a group of sham-operated control rats were treated intravenously with vehicle alone for 14 days. The proximal tibia and first lumbar vertebra, bone sites with hematopoietic marrow, as well as the distal tibia and caudal vertebra, bone sites with primarily fatty marrow, were processed undecalcified for quantitative bone histomorphometry. At the hematopoietic marrow sites, bFGF treatment induced a marked accumulation of osteoid, which calcified during the withdrawal period to result in a significant increase in cancellous bone volume. Osteoblast and osteoid surfaces were increased by at least a factor of 10 at these sites in bFGF-treated ovx rats before declining rapidly during the withdrawal period. In contrast, osteoid volume was negligible in the fatty marrow sites of bFGF-treated ovx rats. Although these animals exhibited a nonsignificant trend for increased cancellous bone volume in the fatty distal tibia during the withdrawal period, no such trend was observed in the fatty caudal vertebra. Indices of bone formation (osteoblast and osteoid surfaces) were significantly increased by bFGF treatment in the fatty distal tibia, which retained some small pockets of hematopoietic cells, but not to the same great extent as in the skeletal sites with hematopoietic marrow. Furthermore, not even a trend for increased osteoblast and osteoid surfaces was observed in the fatty caudal vertebra of bFGF-treated ovx rats. These findings indicate that bFGF is a strong bone anabolic agent at skeletal sites with hematopoietic marrow, but the stimulatory effects of the growth factor on bone formation are greatly attenuated at fatty marrow sites.