Awareness and healthcare seeking behavior of neonatal danger signs, and predictor variables among mothers/caregivers in four developing regional state of Ethiopia.

INTRODUCTION: Mothers/caregivers should be aware of a newborn's danger signs and promptly seek medical attention. Hence, this study assessed mothers'/caregivers' awareness, healthcare seeking behaviors for neonatal danger signs and their determinants in the developing regional state of Ethiopia. METHODS: A community-based cross-sectional study was employed among mothers/caregivers of neonates in the developing regional state of Ethiopia. The sample was determined in collaboration with the Central Statistics Agency of Ethiopia. Stratified multi-stage cluster sampling was used to recruit the sample. Data were collected through an interviewer administered structured questionnaire using a tablet computer. Descriptive statistics and binary logistic regression were applied to identify determinants of awareness and treatment-seeking behavior for neonatal danger signs. RESULTS: The result of the study showed that nearly one-third (32.7%) of the respondents had a good level of awareness of neonatal danger signs, and 69.0% of the respondents had good healthcare-seeking practice about neonatal danger signs. Regional state (Benishangul-Gumuz) [AOR = 1.61; 95% CI (1.09, 2.39)], Muslim's [AOR = 1.75; 95% CI (1.20, 2.55)] and permission to travel to a health facility [AOR = 0.48; 95% CI (0.37, 0.63)] were determinants of mothers'/caregivers' awareness about neonatal danger signs. Antenatal care (ANC) attendance and institutional delivery were shown to have a positive association with neonatal healthcare seeking (AOR = 2.14 and AOR = 2.37, respectively). CONCLUSION: In Ethiopia's developing regional states, mothers/caregivers were remarkably unaware of neonatal danger signs. Region, religion, mothers'/caregivers' age, and need for permission to travel to a health facility were predictor variables for neonatal danger sign awareness. Better healthcare seeking practices, which are determined by ANC attendance and institutional delivery, are observed in these regions. Federal and regional governments should give these regions due attention. Moreover, regional health bureaus and health professionals should tackle the problem by focusing on the identified factors.

Social and behavior change communication competency among front-line healthcare system actors in Ethiopia: a cross-sectional study.

INTRODUCTION: Social and Behavior Change Communication (SBCC) plays a critical role in improving behavior and health outcomes across the continuum of healthcare. Failing to implement tailored SBCC strategies continues to pose a risk of ill health, increase disease burden, and impact the quality life of people. In Ethiopia, front-line healthcare system actors' knowledge and skills about SBCC have not been rigorously assessed. Thus, the current study aimed to assess healthcare system actors' competencies in designing, implementing, monitoring, and evaluating SBCC interventions in Ethiopia. METHODS: A cross-sectional study was conducted between 01 August and 31 October, 2020. Five hundred twenty-eight frontline healthcare system actors in SBCC in Ethiopia were included using simple random sampling technique. Data was collected using a self-administered structured questionnaire adopted from Communication for Change; SBCC capacity assessment tool. Descriptive analysis frequencies, percentages, mean, median, standard deviation (SD), interquartile range (IQR) were employed. Besides correlations and linear regression with robust standard errors were carried out. A 95% confidence interval and a p-value of less than 0.05 were used to declare significant statistical association. RESULTS: A total of 488 frontline workers participated in the study, with a response rate of 92.4%. The mean SBCC knowledge score was 13.2 ± standard deviation (SD) 3.99 and 59.2% scored below 60% of the expected maximum score. The standard mean score of overall skill in SBCC intervention was 2.36 (SD ± 0.98) and 52.6% of them scored below mean score. The SBCC knowledge was significantly predicted by the service year and the regional variation. On the other hand, SBCC skills was significantly predicted by sex, service year, profession, regional variation, and SBCC knowledge. The regional variation was the main predictor of both knowledge and skill on SBCC. The regression models explained 23.1% and 50.2% of the variance in knowledge and skill of SBCC, respectively. CONCLUSION: Front-line healthcare system actors in Ethiopia has low knowledge and skills in SBCC. Variations in SBCC knowledge and skill were observed based on demographic and professionals experience related characteristics. Hence, continuous capacity building activities need to be given to frontline healthcare system actors to enhance their knowledge and skill on SBCC program and achieve the intended health results.

Assessment of willingness and determinants to receive the COVID-19 vaccine among the general population of the Somali region, Eastern Ethiopia: a 2021 cross-sectional study.

OBJECTIVE: This research aimed to assess COVID-19 vaccine acceptance and the factors influencing it among the population of the Somali region in Ethiopia through a cross-sectional COVID-19 survey. DESIGN: Community-based cross-sectional study. SETTING: The survey was conducted in eight selected districts of the Somali region in Ethiopia from 20 October 2021 to 30 October 2021. PARTICIPANTS: Participants were chosen using simple random sampling and data analysis used Stata V.14. Both bivariable and multivariable binary logistic regression methods were applied, with variables having a p value below 0.2 considered for inclusion in the final model, where statistically significant factors were identified at p<0.5. PRIMARY OUTCOME MEASURE: Willingness to take the vaccine. RESULTS: A total of 1010 respondents participated in this study. The proportion of people's willingness to take the vaccine was 65% (95% CI 62 to 68). When you believe moderately or highly that getting a COVID-19 vaccine will protect others (AOR=6.2, 95% CI 1.43 to 26.6) and (AOR=7.2, 95% CI 1.7 to 29.7), then you will protect others as well. Whereas, a desire to get vaccinated little, moderately and highly (AOR=4.3, 95% CI 1.77 to 10.4), (AOR=20, 95% CI 8.5 to 47) and (AOR=147, 95% CI 55 to 392), respectively, was significantly associated with willingness to take the vaccine. Moreover having close family and friends who want them to get a COVID-19 vaccine (AOR=2, 95% CI 1.2 to 3.57) and religious leaders or community leaders (AOR=1.8, 95% CI 1 to 3.1) were significant factors in the multivariable logistic regression model. CONCLUSION: This study found that COVID-19 vaccine acceptance was low in the Somali region. Factors positively linked to one's willingness to get vaccinated included the belief that it protects others, personal desire for vaccination and support from family, friends, community and religious leaders.

BabyWASH and diarrhea prevention practices following multimedia educational intervention in hard-to-reach areas of the Afar and Somali regions of Ethiopia: a mixed-method endline evaluation.

BACKGROUND: Water, sanitation, and hygiene (WASH) interventions, which are specifically targeted towards young children-known as "BabyWASH"-reduce exposure to environmental contamination and prevent microbial burden in their play and feeding environments. The purpose of this endline study was to evaluate the effectiveness and potential sustainability of a multimedia educational intervention in influencing key BabyWASH and diarrhea prevention practices in four hard-to-reach woredas (i.e. administrative districts) of the Afar and Somali regions of Ethiopia. METHODS: A mixed-method, comparative cross-sectional study was conducted, which included 457 household surveys, 16 key informant interviews, and 8 focus group discussions. The multimedia educational intervention comprised: broadcasting radio talk shows and radio spot messages, capacity-building training for community health workers and community leaders, community mobilization campaigns, and the distribution of promotional print media materials. Propensity score matching analysis was used to estimate the effect of the multimedia educational intervention on key BabyWASH and diarrhea prevention attitudes and practices, which was then triangulated with qualitative findings. RESULTS: The multimedia intervention had a significant positive impact on good BabyWASH and diarrhea prevention practices, including appropriate practices of child feces disposal (t-test = 5.17; p < 0.001), handwashing with soap or ash (t-test = 8.85; p < 0.001), maintaining separate playgrounds for young children (t-test = 2.83; p < 0.001), washing of child's body, hands, and faces (t-test = 15.78; p < 0.001), and food hygiene practices (t-test = 2.74; p < 0.05). The findings of the qualitative assessment also revealed that the multimedia intervention packages and the approaches used were successful in influencing key BabyWASH and diarrhea prevention behaviors in the intervention implementation woredas. In addition, providing capacity building training to local actors and community leaders and recording radio talk shows and sharing them with community members were recognized as effective intervention implementation strategies. CONCLUSION: The endline evaluation found that the multimedia educational intervention improved awareness, perception, and practice of BabyWASH and diarrhea prevention behaviors in intervention woredas compared to control woredas. Sanitation and hygiene promotion interventions in pastoralist settings can be effective when using locally and contextually appropriate intervention strategies. However, considerations for integrating both behavioral and structural components in WASH interventions is essential.

Anxiety and Depression among Patients with Chronic Kidney Disease Undergoing Haemodialysis in a Tertiary Care Centre: A Descriptive Cross-sectional Study.

Introduction: Chronic kidney disease is a global public health problem with psychological issues and other adverse issues like renal failure, cardiovascular disease, and premature deaths. This study aimed to find out the prevalence of anxiety and depression among patients with chronic kidney disease undergoing haemodialysis in a tertiary care centre. Methods: A descriptive cross-sectional study was done among patients with chronic kidney disease undergoing haemodialysis in the Department of Medicine, Nephrology unit of a tertiary care centre from December 2020 to June 2021. Ethical approval was taken from the Institutional Review Committee (Reference number: 1712202003). The whole sampling method was used. The diagnosis of anxiety and depression was made using the Nepali version of the Hospital Anxiety and Depression Scale with a cut-off of ≥8 scores. Results: Among 96 patients, the prevalence of anxiety was 66 (68.75%) and that of depression was 74 (77.08%) patients. Conclusions: The prevalence of anxiety and depression was similar to other studies done in similar settings. Keywords: anxiety; chronic kidney disease; depression; hemodialysis.

Severe Stress among Medical Students of Two Medical Colleges: A Descriptive Cross-sectional Study.

Introduction: Mental health problems are common in medical students and there is a high prevalence of psychological morbidity among them. The inability to use effective coping strategies affects the health and academic performance of students. The aim of this study was to find out the prevalence of severe stress among medical students of two medical colleges. Methods: A descriptive cross-sectional study was conducted among medical undergraduates of two medical colleges from 14 September to 14 October 2021. Ethical approval was taken from the Institutional Review Committee (Reference number: 0609202109). Three hundred fifteen students were selected for the study using the proportionate stratified random sampling technique. Perceived Stress Scale was used to assess the level of stress and the Brief Cope Inventory scale was used to assess the coping strategies employed by students during stress. Point estimate and 95% confidence interval was calculated. Results: Among 315 medical students, severe stress was found in 39 (12.38%) (8.76-16.04, 95% Confidence Interval). Conclusions: The prevalence of severe stress among medical students was higher when compared to similar studies done in similar settings. Keywords: coping strategies; medical students; psychological stress.

Association Between Internet Addiction, Depression and Sleep Quality Among Undergraduate Students of Medical and Allied Sciences.

BACKGROUND: The use of the internet is growing rapidly worldwide with easier availability and affordability in developing countries like Nepal. Apart from several benefits, it has also led to deleterious effects on certain individuals' physical and mental well-being. The present study aimed to assess the burden of internet addiction among nursing, dental and medical undergraduates at a medical school, and examine its relationship with depression and sleep quality. METHODS: A cross-sectional study among 494 students pursuing nursing, dental and medical undergraduate courses at the same medical college in Nepal was conducted. The burden of internet addiction, depression, and sleep disturbance was assessed using Young's Internet addiction test, Beck's depression inventory, and Pittsburgh Sleep Quality Index questionnaires respectively. RESULTS: The majority of respondents reported either controlled use of internet or mild problem with internet use. However, 4.7% of respondents reported significant problems due to internet use. Further, about 42.3% reported poor sleep quality, and 8.9% screened positive for depression. In both chi-square and logistic regression analyses, internet addiction was significantly associated with poor sleep quality and depression. CONCLUSION: The study shows that about half of the participants experienced at least some problems and a small but significant proportion of them reported severe problems due to internet use. This warrants the need to address the issue of internet addiction among medical and allied sciences students in Nepal. Further, internet addiction is associated with both depression and poor sleep quality, highlighting a need to develop effective interventions targeting all three problems holistically.

Effect of lockdown on mental health during the COVID-19 pandemic among individuals attending services at a tertiary care center.

BACKGROUND: Lockdown is an emergency measure or condition in which people are temporarily prevented from entering or leaving a restricted area or building during a threat or danger. Since the start of COVID-19 till date, almost one-third of the world's population is under some degree of restriction and lockdown, and the mental health effect of which is something that is being discussed widely. AIM: The study aimed to assess the effect of lockdown on mental health among individuals (patients or accompanying person) seeking services at a tertiary care center. MATERIALS AND METHODS: Kathmandu Medical College is a tertiary care center and a medical college in Kathmandu, Nepal. In this study, we enrolled every 4th individual coming to the hospital's outpatient department registration counter to seek service and giving consent, for the duration of 1 month during the ongoing lockdown period. A semi-structured questionnaire was developed and approved by the department and was used to collect sociodemographic details and to rate the stress level. The General Health Questionnaire (GHQ-12) Nepali version was used to assess psychological well-being of the participants and a score of ≥3 by binary method was taken as positive case. RESULTS: The total number of cases enrolled in the study was 204, out of them 62.2% were male and 32.8% were female and the mean age was 32.03 years. Twenty-three percent (23.5%) had preexisting health conditions. Out of the 204 participants, 67.6% said they were stressed following the lockdown and the mean rated stress was 2.90 in a scale ranging from 1 to 7. The frequently identified stressors were fear of contamination, restricted movement, and for inadequate supplies. Twenty-seven percent said they had some psychological symptoms and the most common symptoms were palpitation and sleep disturbance. Seventy-three individuals (36.5%) were found to have psychiatric problem according to their scores in GHQ-12. Rated stress and GHQ-12 scores were found to be strongly correlated (P = 0.000). Similarly, those who stated "Yes" in psychological symptoms significantly scored higher on GHQ-12 and stress (both P = 0.000). CONCLUSION: The lockdown has caused stress in majority of cases, and a significant number of individuals have diagnosable mental health conditions. Mental health impact of the lockdown is something that needs to be addressed seriously.

Plasmodium helical interspersed subtelomeric family-an enigmatic piece of the Plasmodium biology puzzle.

Plasmodium falciparum (Pf) refurbishes the infected erythrocytes by exporting a myriad of parasite proteins to the host cell. A novel exported protein family 'Plasmodium Helical Interspersed Subtelomeric' (PHIST) has gained attention for its significant roles in parasite biology. Here, we have collected and analysed available information on PHIST members to enhance understanding of their functions, varied localization and structure-function correlation. Functional diversity of PHIST proteins is highlighted by their involvement in PfEMP1 (Pf erythrocyte membrane protein 1) expression, trafficking and switching. This family also contributes to cytoadherence, gametocytogenesis, host cell modification and generation of extracellular vesicles. While the PHIST domain forms the hallmark of this family, existence and functions of additional domains (LyMP, TIGR01639) and the MEC motif underscores its diversity further. Since specific PHIST proteins seem to form pairs with PfEMP1 members, we have used in silico tools to predict such potential partners in Pf. This information and our analysis of structural data on a PHIST member provide important insights into their functioning. This review overall enables readers to view the PHIST family comprehensively, while highlighting key knowledge gaps in the field.

Synthesis of Nucleic Acid Bases by Metal Ferrite Nanoparticles from a Single Carbon Atom Precursor Molecule: Formamide.

The synthesis of prebiotic molecules from simple precursors is believed to be a crucial scheme in order to study the origin of life processes. The present study describes the one-pot synthesis of purine and pyrimidine nucleic acid bases in the presence of pre-biologically significant binary metal oxide nanoparticles, metal ferrites, namely NiFe2O4, CoFe2O4, CuFe2O4, ZnFe2O4 and MnFe2O4. The products identified are cytosine, isocytosine, 4(3H)-pyrimidinone, adenine, hypoxanthine and purine. The ability of isocytosine (a constitutional isomer of cytosine) to recognize cytosine and guanine through normal and reversed Watson-Crick pairing respectively, demonstrates an important storyline for the genesis of ancient nucleic acids. The relevance of other synthesized nucleic acid bases with respect to the origin of life is also discussed. The divalent metal ions in iron oxide make it an appropriate catalytic system because it demonstrates excellent catalytic performance for the nucleic acid bases synthesis with significantly high yield, as compared to pure iron oxide and some other minerals like silica, alumina, manganese oxides and double metal cyanide complexes.

Antibiotic resistance: A cross-sectional study on knowledge, attitude, and practices among veterinarians of Haryana state in India.

AIM: The current study aimed to assess the knowledge, attitude, and practices pertaining to antibiotic usage among the field veterinarians who serve as nodal officers playing a crucial role in disseminating knowledge to the farmers regarding livestock management practices in India. MATERIALS AND METHODS: A pilot study was conducted in which 106 of the 173 field veterinarians of Haryana, India, agreed to contribute through their valuable participation in the study. The collected data were critically analyzed by simple descriptive statistics, and the responses were ranked using Garrett's ranking method. RESULTS: Our study found that most of the clinicians were aware of the fundamental clinical aspects of antibiotic resistance (AR), i.e., the general causes and transmission of resistance, response during treatment failure, and safe disposal of hospital waste. Further, implementation of "antibiotic stewardship" (rational/responsible use of antibiotics) and interruption of AR transmission by means of cross-kingdom pathogens are two ways to restrict the spread of resistant pathogens which were not in the clinical purview of majority of the clinicians. This highlights a lack of awareness and scope of improving clinician's knowledge pertaining to AR. Moreover, we got to know the methodology adopted by farmers for disposal of infected milk from diseased udders as well as their attitude toward diseased and unproductive animals. CONCLUSION: This study provides snippets of the current animal husbandry practices prevalent at the field level which would assist to plug in the gaps of knowledge regarding AR among the veterinarians as well as the general public and serve to reduce its deleterious impacts in Indian animal farming as well as in the world through the concept of "One World, One Health."

Knowledge of Alzheimer's Disease Among Medical Students of a Medical College.

INTRODUCTION: Dementia is a public health concern as the prevalence is increasing worldwide with significant increase being in low-middle income countries. However these countries appear to be less prepared in handling this rise in terms of diagnosis and management. METHODS: This cross-sectional study was conducted in Kathmandu medical College, from June 2017 to July 2017. Purposive sampling was done and the medical students who were in their first and final year of study were included in the study after obtaining an informed consent. RESULTS: Total 185 students were included in the study, 80 (43.24%) from first year and 105 (56.75%) from final year of medical study. The mean score of knowledge among the students was 17.44±2.46; 15.32±1.22 among first year and 19.06±1.87 among the final year students. Majority of the students said they have heard about dementia however, only 3 (3.75%) of first year and 43 (41.9%) from final year students have either attended a class or continuing medical education on dementia Conclusions: The knowledge about dementia was found to be average among medical students but better among final year medical students in comparison to first year. The knowledge was found to be better statistically among those who had either attended a class or continuing medical education on dementia or had exposure through different medias.

Assessing Caregiver Burden in Caregivers of Patients with Schizophrenia and Bipolar Affective Disorder in Kathmandu Medical College.

BACKGROUND: Schizophrenia and bipolar affective disorder are chronic psychiatric illness that requires long term care. This study tends to measure psychological burden and factors associated with it among caregivers of these two illnesses. METHODS: This is a cross- sectional study that included participants by purposive sampling method. Self designed performa was used to collect the socio-demographic details of the caregivers. Modified caregiver strain index was used to assess the overall stress. Beck`s depression inventory and Beck`s anxiety inventory was used to assess depression and anxiety respectively. RESULTS: Hundred caregivers, 50 each of schizophrenia and bipolar affective disorder were enrolled. Seventy-two percent of caregivers were found to have higher level of stress. Twenty-five percent had depression and 29% anxiety related problems. Stress was found to be significantly associated with being in debt, longer duration of illness, education level, marital status, subjective feeling of psychological stress and self- acknowledgement of need of professional help. Caregivers of both group experienced similar level of stress. CONCLUSIONS: Psychological burden is seen to be high in caregivers of patients of Schizophrenia and Bipolar Affective Disorder.

Thermal Condensation of Glycine and Alanine on Metal Ferrite Surface: Primitive Peptide Bond Formation Scenario.

The amino acid condensation reaction on a heterogeneous mineral surface has been regarded as one of the important pathways for peptide bond formation. Keeping this in view, we have studied the oligomerization of the simple amino acids, glycine and alanine, on nickel ferrite (NiFe2O4), cobalt ferrite (CoFe2O4), copper ferrite (CuFe2O4), zinc ferrite (ZnFe2O4), and manganese ferrite (MnFe2O4) nanoparticles surfaces, in the temperature range from 50-120 °C for 1-35 days, without applying any wetting/drying cycles. Among the metal ferrites tested for their catalytic activity, NiFe2O4 produced the highest yield of products by oligomerizing glycine to the trimer level and alanine to the dimer level, whereas MnFe2O4 was the least efficient catalyst, producing the lowest yield of products, as well as shorter oligomers of amino acids under the same set of experimental conditions. It produced primarily diketopiperazine (Ala) with a trace amount of alanine dimer from alanine condensation, while glycine was oligomerized to the dimer level. The trend in product formation is in accordance with the surface area of the minerals used. A temperature as low as 50 °C can even favor peptide bond formation in the present study, which is important in the sense that the condensation process is highly feasible without any sort of localized heat that may originate from volcanoes or hydrothermal vents. However, at a high temperature of 120 °C, anhydrides of glycine and alanine formation are favored, while the optimum temperature for the highest yield of product formation was found to be 90 °C.

Melatonin inhibits snake venom and antivenom induced oxidative stress and augments treatment efficacy.

Snakebite is a neglected health hazard. Its patho-physiology has largely been focused on systemic and local toxicities; whereas, venom and antivenom induced oxidative stress has long been ignored. Antivenom therapy although neutralizes venom lethality and saves many lives, remains ineffective against oxidative stress. This prompted us to complement antivenom with an antioxidant molecule melatonin that would protect against oxidative stress and increase the efficacy of the existing snakebite therapy. Here we show that D. russelli and E. carinatus venoms induce strong oxidative stress that persists even after antivenom administration in mice model. Additionally, antivenoms also induce oxidative stress. Polyvalent antivenom induce more oxidative stress than monovalent antivenom. Strikingly, antivenom and melatonin together not only inhibit venom and antivenom induced oxidative stress but also significantly reduce the neutralizing antivenom dose. This study provides a therapeutic potential for enhancing the existing snakebite therapy. The combined treatment of antivenom+melatonin would prevent the upsurge of oxidative stress as well as minimize the antivenom load. Thus the investigation offers immense scope for physicians and toxinologists to reinvestigate, design new strategies and think beyond the conventional mode of antivenom therapy.

NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction.

Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom.

Lupeol derivative mitigates Echis carinatus venom-induced tissue destruction by neutralizing venom toxins and protecting collagen and angiogenic receptors on inflammatory cells.

BACKGROUND: Echis carinatus bite is a serious threat in South-Asian countries including India, as it causes highest number of deaths and terrifying long-term tissue destruction at the bitten site. Although venom metalloproteinases and hyaluronidases are the suggested key players, studies on the effect of venom on polymorphonuclear cells, peripheral blood mononuclear cells and platelets, and their role in long-term tissue destruction are still in infancy. While, the effect of venom on collagen receptors, integrin α2ß1/GP VI/DDR1 and CX3CR1 chemokine receptor present on these cells is an untouched area. METHODS: Lupeol, lupeol acetate, its synthetic derivatives 2-8 were screened for inhibition of E. carinatus venom induced-hemorrhage in mouse model where compound 8 was found to be the most potent. Further, compound 8 efficiently neutralized venom induced hemorrhage, edema, dermonecrosis, myonecrosis, myotoxicity, pro-coagulant, oxidative stress, inflammatory cytokines and cleavage of collagen and CX3CR1 receptors on inflammatory cells in in vivo, in silico, ex vivo and in vitro studies. CONCLUSIONS: This study for the first time demonstrated the cleavage of collagen receptors and the receptor for angiogenesis and wound healing by the venom and its inhibition by compound 8, as these are important for firm adhesion of inflammatory cells at the damaged site to resolve inflammation and promote tissue repair. GENERAL SIGNIFICANCE: This study provides a lead in venom pharmacology, wherein, compound 8 could be a therapeutic agent for the better management of viper venom-induced long-term tissue destruction.

Oxidative stress-induced methemoglobinemia is the silent killer during snakebite: a novel and strategic neutralization by melatonin.

Oxidative stress-induced methemoglobinemia remained an untouched area in venom pharmacology till date. This study for the first time explored the potential of animal venoms to oxidize hemoglobin to methemoglobin. In in vitro whole-blood assay, methemoglobin forming ability of venoms varied as Naja naja > Ophiophagus hannah > Echis carinatus > Daboia russellii > Apis mellifera > Mesobuthus tamulus > Hippasa partita. Being highly potential, N. naja venom was further studied to observe methemoglobin formation in RBCs and in combinations with PMNs and PBMCs, where maximum effect was observed in RBCs + PMNs combination. Naja naja venom/externally added methemoglobin-induced methemoglobin formation was in parallel with ROS generation in whole blood/RBCs/RBCs + PMNs/RBCs + PBMCs. In in vivo studies, the lethal dose (1 mg/kg body weight, i.p.) of N. naja venom readily induced methemoglobin formation, ROS generation, expression of inflammatory markers, and hypoxia-inducible factor-3α. Although the mice administered with three effective doses of antivenom recorded zero mortality; the methemoglobin and ROS levels remained high. However, one effective dose of antivenom when administered along with melatonin (1:50; venom/melatonin, w/w), not only offered 100% survival of experimental mice, but also significantly reduced methemoglobin level, and oxidative stress markers including hypoxia-inducible factor-3α. This study provides strong drive that, complementing melatonin would not only reduce the antivenom load, but for sure greatly increase the success rate of antivenom therapy and drastically minimize the global incidence of snakebite deaths. However, further detailed investigations are needed before translating the combined therapy towards the bed side.

Formamide-based synthesis of nucleobases by metal(II) octacyanomolybdate(IV): implication in prebiotic chemistry.

We propose that double metal cyanides that formed in primeval seas might have played a vital role in chemical evolution and the origin of life. An array of metal octacyanomolybdates (MOCMos) has been synthesized, and their role as catalyst in the formation of nucleobases from formamide has been studied. Formamide, a hydrolysis product of HCN, was taken as starting material for the formation of nucleobases. Recent studies support the presence of formamide on some celestial bodies. Metal octacyanomolybdates, MOCMos (M = Mn, Fe, Co, Ni, Cu, Zn, Cd), are found to be highly efficient catalysts in the conversion of formamide into different nucleobases. Neat formamide is converted to purine, 4(3H)-pyrimidinone, cytosine, adenine, 9-(hydroxyacetyl)-purine, and thymine in good yield when using MOCMos. The products formed were characterized by high-performance liquid chromatography and electrospray ionization mass spectrometry techniques. The results of our study show that insoluble double metal cyanides might have acted as efficient catalysts in the synthesis of various biologically important compounds (e.g., purines, pyrimidines) under primeval seas on Earth or elsewhere in our solar system.