INVESTIGATION OF THE NEUROPROTECTIVE EFFECT OF LINAGLIPTIN AND CELIPROLOL IN RESERPINE-INDUCED OROFACIAL DYSKINESIA AND ROTENONE-INDUCED NEURODEGENERATION IN RATS

Objective: Linagliptin, an anti-diabetic agent, proven to play an important role in regulating neuronal plasticity and reduce apoptosis and neuroinflammation by activating downstream AMPK/Sirt 1 pathway, which protects mitochondrial function and suppresses intracellular ROS accumulation and shows antioxidant action. Celiprolol, a β-1selective adrenoceptor blocker used as an anti-hypertensive agent, possesses a direct scavenging activity on oxygen radicals with antioxidant properties. The current study was designed to investigate the combined neuroprotective effect of linagliptin and celiprolol. Methods: Wistar rats of either sex were divided into different groups (n = 6). Eight groups each for Reserpine induced orofacial dyskinesia model and Rotenone induced neurodegeneration model to mimic Parkinson’s like conditions and treated or not with different doses of linagliptin and celiprolol. 24 h after the last dose, animals were subjected to behavioral, biochemical and histopathological evaluations. The data were analyzed by ANOVA and Bonferroni multiple comparison test. Results: Reserpine treatment increased VCMs, tongue protrusion and decreased locomotor activity. Rotenone treatment decreases the motor activity and exploratory ability of the animals. Reserpine as well as rotenone treatments decrease catalase, GSH, SOD and increase the LPO levels as compared to sham group animals. Reserpine and rotenone also showed the presence of ghost cells and vacuolated cytoplasm. Linagliptin and celiprolol alone as well as in combination normalized the behavioral, biochemical and histopathological complications. Conclusion: Linagliptin and Celiprolol showed neuroprotection by antioxidant activity as well as improved reserpine and rotenone-induced behavioral deficits. Both drugs have tenacious potential and can be used clinically with some further investigations

PROTECTIVE EFFECT OF NEBIVOLOL ON ALUMINIUM-INDUCED NEUROBEHAVIORAL AND BIOCHEMICAL ALTERATIONS IN RATS

Objective: The present study was designed to investigate the neuroprotective potential of nebivolol, a β1 adrenergic blocker on aluminium-induced neurobehavioral and biochemical alterations in rats. Methods: The neurotoxicity was induced by administration of aluminium (50 mg/kg/day, p.o.) for 5 weeks. Nebivolol was administered at a dose of 10 mg/kg, p.o. for 5 weeks. Behavioral assessments were done by using open field test and modified elevated plus maze (mEPM) test. At the end of the study, oxidative stress parameters were determined and histopathological studies of cerebral cortex of rat brains were performed. Results: Aluminium chloride treated rats showed significant reduction in motor activity in open field test and memory impairment in mEPM test as compared to control group. Nebivolol significantly reversed these parameters and restored brain antioxidant defensive enzymes with reduction in lipid peroxidation. The neurotoxicity was confirmed by the histopathological analysis of cerebral cortex of rat brains. Aluminium treated animals showed presence of ghost cells, vacuolated cytoplasm and haemorrhage in rat cerebral cortex, indicating neurotoxicity. Nebivolol attenuated all these changes. Thus, the potential of nebivolol to prevent aluminium-induced neurotoxicity was also reflected at microscopic level, indicative of its neuroprotective effects. Conclusion: Nebivolol showed significant antioxidant and neuroprotective activities against aluminium-induced neuronal degeneration. The results of the present study strengthen oxidative stress hypothesis of aluminium-induced neurotoxicity and suggest beneficial role of nebivolol in the treatment of neurodegenerative disorders

Knowledge of health workers relating to sepsis awareness and management in Lambaréné, Gabon

Background In 2016, the third international consensus definitions for sepsis and septic shock (Sepsis-3) task force provided revised definitions for sepsis and septic shock. This study explores knowledge regarding sepsis among health workers in Lambaréné, Gabon. Methods We conducted a self-administered questionnaire-based survey about sepsis among health workers from the referral regional hospital, the research center, and primary care health facilities in the Lambaréné region. Participants were from the referral regional hospital, the research center, and primary health care facilities. A score of one was given to each correct answer. The global score out of a possible score of twenty was calculated, and the proportion of correct responses was determined. Results A total of 115 health workers (physicians, nurses and assistant nurses) completed the questionnaire, of which 48.7% (56/115) provided a valid definition of sepsis, but 74% (85/115) had never heard about the quick Sequential Organ Failure Assessment (qSOFA) score. The proportion of correct answers was comparable across the three health profession categories. The median global score across all health workers was 11 [IQR, 9-14.5] out of 20. Physicians attained higher global scores [14 (IQR, 11-15)] than assistant nurses [11 (IQR, 8-13), P=0.007]; their global score was comparable to that of nurses. Conclusion There are considerable knowledge gaps regarding sepsis among health workers in Lambaréné, potentially impairing the prompt recognition and management of sepsis. There is a need to establish periodic up-to-date training to improve sepsis knowledge

A nurse‐led intervention improves detection and management of AKI in Malawi

BACKGROUND: Acute kidney injury is common and has significant impact on mortality and morbidity. There is a global drive to improve the lack of knowledge and understanding surrounding the recognition, diagnosis and management of patients with AKI in resource poor healthcare systems. OBJECTIVES: We propose a nurse‐led education programme to medical and nursing staff of the Queen Elizabeth Central Hospital (QECH) in Blantyre, Malawi, will improve the overall care and understanding of patients with AKI that will still be effective 3 months later. METHODS: This was a three phase, prospective interventional pilot study which evaluated base line knowledge and clinical practice amongst healthcare workers, provided a comprehensive combination nurse‐led class room and ward based teaching programme and evaluated the change in knowledge and clinical management of patients in the high dependency areas of the hospital immediately, and 3 months, after the teaching intervention. RESULTS: The nurse‐led intervention significantly improved the healthcare workers attitudes towards detecting or managing patients with suspected AKI (p < 0.0001). There were also significant improvements in the completion of fluid charts and recording of urine output (p < 0.0001), corner stones of AKI management. Knowledge and clinical intervention was still present three months later. There was however little change in the understanding that AKI could be a significant clinical problem in QECH and that it may have a major impact on mortality and working practice and this needs to be addressed in future teaching programmes. CONCLUSIONS: A low cost, nurse‐led AKI educational intervention improved the knowledge and management of AKI at QECH, which was still evident 3 months later

Diagnostic Performance of a Saliva Urea Nitrogen Dipstick to Detect Kidney Disease in Malawi

Introduction: Kidney disease (KD), including acute kidney injury, is common, severe and leads to significant mortality in the developing world. However, simple tools to facilitate diagnosis and guide treatment are lacking. We studied the diagnostic performance of saliva urea nitrogen (SUN) measured by dipstick to diagnose KD in a low-resource setting. Methods: Medical admissions to a tertiary hospital in Malawi had serum creatinine tested at presentation; SUN was measured using a dipstick. Patients with serum creatinine above normal range underwent serial measurements of SUN and blood urea nitrogen for up to 7 days. Hospital outcome was recorded in all patients. Results: A total of 742 patients were included (age 41 ± 17·3 years, 56.1% male); 146 (19.7%) had KD, including 114 (15.4%) with acute kidney injury. SUN >14 mg/dl had a sensitivity of 0.72 and a specificity of 0.87 to diagnose KD; specificity increased to 0.97 when SUN levels were combined with self-reported urine output. The diagnostic performance of SUN was comparable with the one of blood urea nitrogen (SUN area under curve, 0.82; 95% confidence interval, 0.78–0.87; blood urea nitrogen area under curve, 0.82; 95% confidence interval, 0.59–1.0). SUN >14 mg/dl on admission was an independent predictor of all-cause mortality (hazard ratio = 2.43 [95% confidence interval, 1.63–3.62]). Discussion: SUN measured by dipstick can be used to identify patients with KD in a low-resource setting. SUN is an independent predictor of mortality in this population

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Muon Collider Forum report

A multi-TeV muon collider offers a spectacular opportunity in the direct exploration of the energy frontier. Offering a combination of unprecedented energy collisions in a comparatively clean leptonic environment, a high energy muon collider has the unique potential to provide both precision measurements and the highest energy reach in one machine that cannot be paralleled by any currently available technology. The topic generated a lot of excitement in Snowmass meetings and continues to attract a large number of supporters, including many from the early career community. In light of this very strong interest within the US particle physics community, Snowmass Energy, Theory and Accelerator Frontiers created a cross-frontier Muon Collider Forum in November of 2020. The Forum has been meeting on a monthly basis and organized several topical workshops dedicated to physics, accelerator technology, and detector R&amp;D. Findings of the Forum are summarized in this report

Transcriptional and genomic parallels between the monoxenous parasite Herpetomonas muscarum and Leishmania

Trypanosomatid parasites are causative agents of important human and animal diseases such as sleeping sickness and leishmaniasis. Most trypanosomatids are transmitted to their mammalian hosts by insects, often belonging to Diptera (or true flies). These are called dixenous trypanosomatids since they infect two different hosts, in contrast to those that infect just insects (monoxenous). However, it is still unclear whether dixenous and monoxenous trypanosomatids interact similarly with their insect host, as fly-monoxenous trypanosomatid interaction systems are rarely reported and under-studied–despite being common in nature. Here we present the genome of monoxenous trypanosomatid Herpetomonas muscarum and discuss its transcriptome during in vitro culture and during infection of its natural insect host Drosophila melanogaster. The H. muscarum genome is broadly syntenic with that of human parasite Leishmania major. We also found strong similarities between the H. muscarum transcriptome during fruit fly infection, and those of Leishmania during sand fly infections. Overall this suggests Drosophila-Herpetomonas is a suitable model for less accessible insect-trypanosomatid host-parasite systems such as sand fly-Leishmania