Methods: This study investigated the cytotoxic effect of the venom from Trimeresurus purpureomaculatus, the mangrove pit viper (also known as shore pit viper) which is native in Malaysia, across a panel of human cancer cell lines from breast, lung, colon and prostate as well as the corresponding normal cell lines of each tissue.
Results: The venom exhibited dose-dependent cytotoxic activities on all cell lines tested, with median inhibition concentrations (IC50) ranging from 0.42 to 6.98 µg/mL. The venom has a high selectivity index (SI = 14.54) on breast cancer cell line (MCF7), indicating that it is significantly more cytotoxic toward the cancer than to normal cell lines. Furthermore, the venom was fractionated using C18 reversed-phase high-performance liquid chromatography and the anticancer effect of each protein fraction was examined. Fraction 1 that contains a hydrophilic low molecular weight (approximately 7.5 kDa) protein was found to be the most cytotoxic and selective toward the breast cancer cell line (MCF7). The protein was identified using liquid chromatography-tandem mass spectrometry as a venom disintegrin, termed purpureomaculin in this study.
Conclusion: Taken together, the findings revealed the potent and selective cytotoxicity of a disintegrin protein isolated from the Malaysian T. purpureomaculatus venom and suggested its anticancer potential in drug discovery.
RESULTS: Increases in homogenization pressure and emulsifier concentration were observed to have significant (P 0.05) differences between the prepared and commercial LNDCs in terms of their color, appearance, and overall acceptability.
CONCLUSION: Shelf-stable LNDCs with qualities comparable to commercial LNDC were successfully fabricated. Valuable insights into the effects of homogenization pressure, oil type, and emulsifier concentration, as well as functionality and consumer acceptance of the LNDCs when added into black coffee, were obtained. © 2020 Society of Chemical Industry.
METHODS: This is a prospective observational study of 201 patients who underwent endoscopic nasojejunal wire-guided feeding tube insertions for obstruction of either the esophagus or the stomach including both benign and malignant pathologies between January 2015 to June 2018 in Hospital Sungai Buloh and Hospital Sultanah Aminah, Malaysia. The indications for tube insertion, insertion technique, and tube-related problems were described.
RESULTS: The nasojejunal tube was used to establish enteral feeding in patients with obstructing tumors of the distal esophagus in 65 patients (32.3%) and gastric outlet obstruction in 72 patients (35.8%). There were 54 patients (26.9%) who required reinsertion. The most common reason for reinsertion was unintentional dislodgement, where 32 patients (15.9%) followed by tube blockage 20 patients (10.0%). Using our method of advancement under direct vision, we had only 2 cases of malposition due to severely deformed anatomy. We had no incidence of aspiration in this group of patients and overall, the patients tolerated the tube well.
CONCLUSIONS: The novel nasojejunal feeding tube with gastric decompression function is a safe and effective method of delivery of enteral nutrition in patients with upper gastrointestinal obstruction. These tubes if inserted properly are well tolerated with almost no risk of malposition and are tolerated well even for prolonged periods of time until definitive surgery could be performed.
METHODS: Participants were recruited as part of a cohort study exploring the syndemic risks associated with HIV acquisition among young GBQ men in Singapore. We examined their levels of internalised, perceived, experienced homophobia, as well as their health behaviours and suicidal tendencies. Two separate variables were also self-reported by the participants - the age of questioning of sexual orientation and the age of acceptance of sexual orientation. We subsequently recoded a new variable, delayed acceptance of sexual orientation, by taking the difference between these two variables, regressing it as an independent and dependent variable to deduce its psychosocial correlates, as well as its association with other measured instruments of health.
RESULTS: As a dependent variable, delayed acceptance of sexual orientation is positively associated with an increase of age and internalised homophobia, while being negatively associated with reporting as being gay, compared to being bisexual or queer. As an independent variable, delayed acceptance of sexual orientation was associated with a delayed age of coming out to siblings and parents, suicide ideation, historical use of substances including smoking tobacco cigarettes and consuming marijuana, as well as reporting higher levels of experienced, internalised and perceived homophobia.
CONCLUSION: Greater levels of early intervention and efforts are required to reduce the heightened experience of minority stress resulting from communal and institutional hostilities. Areas of improvement may include community-based counselling and psychological support for GBQ men, while not forsaking greater education of the social and healthcare sectors. Most importantly, disrupting the stigma narrative of a GBQ 'lifestyle' is paramount in establishing an accepting social environment that reduces the health disparity faced by GBQ men.
BIOLOGICAL SIGNIFICANCE: Comprehensive venom proteomes of D. russelii from different locales will facilitate better understanding of the geographical variability of the venom in both qualitative and quantitative terms. This is essential to provide scientific basis for the interpretation of differences in the clinical presentation of Russell's viper envenomation. The study revealed a unique venom proteome of the Pakistani D. russelii from the wild (Indus Delta), in which PLA2 predominated (~60% of total venom proteins). The finding unveiled remarkable differences in the venom compositions between the wild (present study) and the captive specimens reported previously. The integration of toxicity tests enabled the correlation of the venom proteome with the envenoming pathophysiology, where the venom showed potent lethality mediated through coagulopathic activity. The Indian VINS Polyvalent Antivenom (VPAV) showed binding activity toward the venom protein antigens; however the immunorecognition of small proteins and PLA2-dominating fractions was low to moderate. Consistently, the antivenom neutralized the toxicity of the wild Pakistani Russell's viper venom at moderate efficacies. Our results suggest that it may be possible to enhance the Indian antivenom potency against the Pakistani viper venom by the inclusion of venoms from a wider geographical range including that from Pakistan into the immunogen formulation.
BIOLOGICAL SIGNIFICANCE: This study reveals the compositional details of the venom proteome of Pakistani spectacled cobra (Naja naja). The protein subtypes, proteoforms, and relative abundances of individual proteins were comprehensively revealed in this study, following a venom decomplexing proteomic approach. The Pakistani cobra venom is unique among the rest of the N. naja venom composition reported thus far, as it contains a high abundance of alpha-neurotoxins (predominated by long neurotoxins); these are highly potent post-synaptic neuromuscular blockers that cause paralysis and are principal toxins that account for the high lethality of the venom (LD50=0.2μg/g in mice). In contrast, previous reports showed that the N. naja venoms of India and Sri Lanka had a lower content of neurotoxins and a relatively higher value of LD50. The Pakistani cobra venom demonstrated sufficient immunoreactivity toward three antivenom products manufactured outside Pakistan (including the Indian product VINS), however the potency of antigen binding was the highest toward Naja kaouthia monovalent antivenom, a heterologous antivenom raised against a long neurotoxin-predominated venom of the Thai monocled cobra. From the practical standpoint, the findings indicate that the treatment of N. naja envenomation in Pakistan may be improved by the production of a locale-specific antivenom, in which the antivenom produced contains more antibodies that can target and react more specifically with the highly abundant lethal neurotoxins in the Pakistani N. naja venom.
METHODS: The venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol.
RESULTS: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately.
CONCLUSION: Considering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.
METHODS: The Promoting Independence in Seniors with Arthritis (PISA) study is a longitudinal observational study of individuals with and without knee pain and knee OA recruited from the orthopaedics clinic of the Universiti Malaya Medical Centre and the local hospital catchment. Patients were diagnosed with OA based on the American College of Rheumatology (ACR) criteria, the presence of knee pain, and a history of physician-diagnosed knee OA. Psychosocial parameters were measured using validated measures for social participation, independence, and ability to perform activities of daily living, and life satisfaction.
RESULTS: Of the 230 included participants, mean age was 66.9 years (standard deviation: 7.2) and 166 (72.2%) were women. Kappa agreement between ACR criteria and knee pain was 0.525 and for ACR and physician-diagnosed OA it was 0.325. Binomial logistic regression analysis showed that weight, anxiety, and handgrip strength (HGS) were predictive of ACR OA. Knee pain was only predicted by HGS but not weight and anxiety. Physician-diagnosed OA was predicted by weight and HGS but not anxiety. HGS was predictive of ACR OA, knee pain, and physician-diagnosed OA.
CONCLUSION: Our study showed that the characteristics of patients with OA are different, physically and psychosocially, depending on the criteria used. Poor agreement was observed between radiological diagnosis and the other diagnostic criteria. Our findings have important implications for the interpretation and comparison of published studies using different OA criteria.