Identification of possible natural compounds as potential inhibitors against Plasmodium M1 alanyl aminopeptidase

Malaria is a major tropical health problem with a 29% mortality rate among people of all ages; it also affects 35% of the children. Despite the decrease in mortality rate in recent years, malaria still results in around 2000 deaths per day. Malaria is caused by Plasmodium parasites and is transmitted to humans via the bites from infected female Anopheles mosquitoes during blood meals. There are five different Plasmodium species that can cause human malaria, which include Plasmodium falciparum, Plasmodium vivax, Plasmodium malariae, Plasmodium ovale and Plasmodium knowlesi. Among these five species, the most pathogenic ones are Plasmodium falciparum and Plasmodium vivax. Malaria is usually hard to diagnose because the symptoms are not exclusive to malaria and very similar to flu, e.g., fever, muscle pain, and chills, which lead to the misdiagnosis of malaria cases. Malaria is lethal if not treated because it can cause severe complications in the respiratory tract, liver, metabolic acidosis, and hypoglycemia. The malaria parasite life cycle includes two types of hosts, i.e., a human host and female Anopheles mosquito host. Malaria continuously develops resistance to the available drugs, which is one of the major challenges in disease control. This situation confirms the need to develop new drugs that target virulence factors of malaria. The malarial parasite has three main life cycle stages, which include the host liver stage, host blood stage and vector stage. In the blood stage, parasites degrade hemoglobin to amino acids, which is important as these parasites cannot produce their own amino acids. Different proteases are involved in this hemoglobin degradation process. M1 alanyl aminopeptidase is one of these proteases involved at the end of hemoglobin degradation. This study focused on M1 alanyl aminopeptidase as a potential drug target. M1 alanyl aminopeptidase consists of four domains: N-terminal domain, catalytic domain, middle domain and C-terminal domain. The catalytic domain remains conserved among different Plasmodium species. Inhibition of this enzyme might prevent Plasmodium growth as it can’t produce its own amino acids. In this study, sequence analysis was carried out in both human and Plasmodium M1 alanyl aminopeptidase to identify conserved and divergent regions between them. 3D protein models of the M1 alanyl aminopeptidase from Plasmodium species were built and validated. Then the generated models were used for virtual screening against 623 compounds retrieved from the South African Natural Compounds Database (SANCDB, https://sancdb.rubi.ru.ac.za/). Virtual screening was done using blind and targeted docking methods. Docking was used to identify compounds with selective high binding affinity to the active site of the parasite protein. In this study, one SANCDB compound was selected for each protein: SANC00531 was selected against P. falciparum M1 alanyl aminopeptidase, SANC00469 against P. knowlesi, SANC00660 against P. vivax, SANC00144 against P. ovale and SANC00109 against P. malariae. It was found that Plamsodium M1 alanyl aminopeptidase can be used as a potential drug target as it showed selective binding against different inhibitor compounds. This result will be investigated in future work though molecular dynamic analysis to investigate the stability of protein-ligand complexes

Functional neuroimaging of conversion disorder: The role of ancillary activation

AbstractBackgroundPrevious functional neuroimaging studies investigating the neuroanatomy of conversion disorder have yielded inconsistent results that may be attributed to small sample sizes and disparate methodologies. The objective of this study was to better define the functional neuroanatomical correlates of conversion disorder.MethodsTen subjects meeting clinical criteria for unilateral sensory conversion disorder underwent fMRI during which a vibrotactile stimulus was applied to anesthetic and sensate areas. A block design was used with 4 s of stimulation followed by 26 s of rest, the pattern repeated 10 times. Event-related group averages of the BOLD response were compared between conditions.ResultsAll subjects were right-handed females, with a mean age of 41. Group analyses revealed 10 areas that had significantly greater activation (p < .05) when stimulation was applied to the anesthetic body part compared to the contralateral sensate mirror region. They included right paralimbic cortices (anterior cingulate cortex and insula), right temporoparietal junction (angular gyrus and inferior parietal lobule), bilateral dorsolateral prefrontal cortex (middle frontal gyri), right orbital frontal cortex (superior frontal gyrus), right caudate, right ventral-anterior thalamus and left angular gyrus. There was a trend for activation of the somatosensory cortex contralateral to the anesthetic region to be decreased relative to the sensate side.ConclusionsSensory conversion symptoms are associated with a pattern of abnormal cerebral activation comprising neural networks implicated in emotional processing and sensory integration. Further study of the roles and potential interplay of these networks may provide a basis for an underlying psychobiological mechanism of conversion disorder

Sensitivity and Specificity of Cystatin C in Detecting Early Renal Impairment in Hypertensive Pregnancies

Purpose: To determine the cutoff point of cystatin C for the detection of renal impairment in hypertensive pregnancies.Methods: A cross-sectional study was conducted in an antenatal clinic and ward at Hospital Universiti Sains Malaysia, Kelantan, Malaysia from January 2009 until January 2010. Sixty four pregnant patients beginning at 2nd trimester, aged of 16 to 55 years and hypertensive, including gestational hypertension, chronic hypertension with superimposed preeclampsia, preeclampsia and unclassified hypertension, were included in the study. Consenting patients were required to provide 5 ml of blood and 24-h urine. Serum and reagent, N Latex cystatin C, were equilibrated at room temperature and measured by particle-enhanced nephelometric immunoassay (PENIA) using a BN II Dade Behring Nephelometer SystemResults: The mean age of the patients was 37.06 ±4.32 (range: 24 to 46 years). A majority (64.1 %) of the patients were in the second trimester of pregnancy and delivered in the gestational period of 38 - 40 weeks (54.7 %). The number of patients in chronic kidney disease (CKD) stages I, II, III, IV and V were 25 (39.1 %), 18 (28.1 %), 18 (28.1 %), 2 (3.1 %) and 1 (1.6 %), respectively. The mean systolic blood pressure was 149.59 ± 18.79 mm Hg, and diastolic blood pressure 91.53 ± 10.33 mm Hg. The cutoff point in detecting renal impairment using cystatin C was &gt; 0.74 with 84.6 % sensitivity and 86.7 % specificity for second trimester and &gt; 0.81 with sensitivity of 76.9 % and specificity of 60.0 % in detecting renal impairment for third trimester.Conclusion: The cutoff point in detecting renal impairment for second trimester is better than for third trimester since it maximizes the value of sensitivity and specificity.Keywords: Cystatin C, Sensitivity, Specificity, Renal impairment, Hypertension; Pregnanc

The protective effects of adenosine deaminase inhibitor and ouercetin against hepatocellular carcinoma induced by thioacetamide in male rats via downregulation of iNOS, Ki67 and Pan-CK

The liver is the largest and most vulnerable organ in the body, several factors can cause liver cirrhosis and the onset of hepatocellular carcinoma. This study aims to investigate the possibility for adenosine deaminase inhibitor (EHNA) which reduces liver injury, neutrophil infiltration and the levels of proinflammatory cytokines and also it is considering as a target of liver cirrhosis and beginning of hepatocellular carcinoma protective, quercetin which is one of the most common flavonoids has an antioxidant, antitumor and chemopreventive effect on the liver-induced preneoplastic lesions and their combination against thioacetamide as a hepatotoxic and a carcinogenic compound. Biochemical, histopathological and immunohistochemical studies were carried out on male albino rats model to evaluate this possibility. Thioacetamide-treated rats showed a significant increase in liver function tests, alpha-fetoprotein level, expression of inducible Nitric Oxide Synthesis (iNOS), Ki67 and Pan-Cytokeratin (Pan-CK) in hepatic tissue of rats. The results of the present study show that treatment with quercetin, EHNA or their combination attenuated changes in liver functions, histopathological changes, reduced collagen deposition and decreased the expression of iNOS, Ki67 and Pan-CK induced by thioacetamide

Factors Associated with Fathers’ Attendance in a Latino Family Obesity Prevention Program

Community-based programs may contribute to Latino pediatric obesity prevention; however, attendance remains low. This study aimed to identify factors associated with Latino father/male caregiver attendance in family-based adolescent obesity prevention programs conducted as part of a randomized controlled trial. The study used cross-sectional data from 137 fathers in the program, involving eight weekly sessions to improve their children’s energy balance-related behaviors. Evaluation data were collected at baseline and post-intervention. Fathers in a waitlisted control group attended sessions after post-intervention data collection. Attendance patterns were identified using cluster analysis: consistently high attendance (50% of fathers), declining attendance (19%), and non-attendance (31%) clusters. Multinomial logistic regression was used to examine associations between attendance patterns and variables. Compared to consistently high attendance, fathers in the non-attendance cluster were more likely to have been assigned to the control group (odds ratio [OR] = 7.86, p \u3c 0.001), tended to have lower household income (OR = 2.50, p = 0.098), and attended the program at a site where the program occurred weekdays (OR = 0.35, p = 0.094). Maintaining contact during waiting periods and providing sessions online or during weekends could reduce non-attendance by enhancing convenience for low-income fathers working multiple jobs

Paliperidone 3-Month Injection for Treatment of Schizophrenia: A Narrative Review

Given the typical age onset of schizophrenia, there are tremendous economic and social impacts that extend beyond the person and their families. One critical determinant of the diseases\u27 impact is the patient\u27s adherence to antipsychotic drug treatment. Approved in 2015 for the treatment of schizophrenia, paliperidone palmitate (Invega Trinza, a 3-month injection, noted as PP3M) is a second-generation long-acting injectable antipsychotic medication. Among the different formulations offered for palmitate paliperidone, including the 1 and 3-month formulations, the longer duration 3-month formulation was better at preventing relapse in schizophrenic patients. To date, different formulations of palmitate paliperidone that have been studied on relapse episodes of schizophrenia include once-daily extended-release oral paliperidone (ORAL paliperidone), once-monthly paliperidone palmitate (PP1M), and once-every-3-months paliperidone palmitate (PP3M). Post-hoc analyses show that patients who were withdrawn from PP1M paliperidone had the least risk of relapse, followed by patients withdrawn from PP3M and patients withdrawn from ORAL paliperidone. PP3M was better at preventing relapse compared to ORAL paliperidone. The results demonstrated that 50% of patients who were withdrawn from ORAL paliperidone, PP1M, or PP3M remained relapse-free for ~2, 6, and 13 months, respectively. Compared to PP1M, PP3M is just as safe and effective and has the added advantage of increased adherence related to a longer dose interval, decreasing the risk of relapse

Differences in reporting food insecurity and factors associated with differences among Latino fathers and mothers

Food security status has been assessed as a representative score for households; however, different members in the same household may perceive and report food insecurity differently. A high prevalence of food insecurity has been reported among Latino households, therefore understanding differences in reporting food insecurity by Latino father-mother dyads may improve accuracy of assessment and plans to address food insecurity. This study aimed to 1) determine demographic characteristics and/or food-related factors associated with perceptions of food security status among Latino father-mother dyads, and 2) identify factors associated with discordance in perceptions of food insecurity between dyads. Baseline data were used from a community-based, youth obesity prevention program among Latino families (n = 106 father-mother dyads). Food security was assessed with a 2-item food insecurity screen. Logistic regression models were used to evaluate associations between reporting food security status and predictor variables for fathers, mothers, and dyad-discordant responses. Food insecurity was reported by 39% of fathers and 55% of mothers. Adjusted odds of reporting food insecurity were significantly higher for fathers perceiving their neighborhood was unsafe vs. safe (OR: 3.7, p < 0.05) and reporting lower vs. higher household income (OR: 3.2, p < 0.05). Adjusted odds of reporting food insecurity were significantly higher for mothers perceiving their neighborhood was unsafe vs. safe (OR: 4.1, p < 0.01) and reporting lower vs. higher home availability of fruit and vegetable (OR: 5.5, p < 0.01). Dyad discordance in reporting food security status occurred in 24% of the dyads. Adjusted odds of dyad discordant reports of food insecurity status were significantly higher for dyads reporting discordant responses regarding previous nutrition education (OR: 3.4, p < 0.05) and higher home fruit and vegetable accessibility (OR: 3.1, p < 0.05) compared to dyads reporting concordant responses. Among the 28 dyads who reported discordant nutrition education participation, 21 reported that fathers had never participated but mothers had participated more than once. Differential factors were associated with reporting food security among Latino father-mother dyads. Nutrition education for fathers that improves awareness of home food supplies and a better understanding of how food accessibility influences maternal perceptions may improve dyad discordance in reporting household food security.https://doi.org/10.1186/s12889-021-10971-

Selective serotonin reuptake inhibitors and adverse effects: A narrative review

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs

Development of low absorption and high-resistant sodium acetate concrete for severe environmental conditions

This research presents new insight on the performance of concrete when integrated with sodium acetateand cured under extremely harsh environmental conditions: freezing temperature of 25°C and hottemperature of 60°C. Mechanical properties, water absorption, microstructural analysis and interactionmechanism of concrete and sodium acetate were evaluated by conducting the compressive strength test,Initial Surface Absorption Test (ISAT), Scanning Electron Microscope (SEM) analysis and Fourier-transform Infrared Spectroscopy (FTIR) analysis. Despite the harsh curing conditions, results showedan enhancement of 64% in compressive strength when 4% (based on the weight of cement) sodium acet-ate is incorporated within concrete with w/c ratio of 0.32 and cured under temperature of 60°C. Also,water absorption was observed to decrease by more than 79% when 2% sodium acetate is added to con-crete with w/c ratio of 0.32. SEM and FTIR analyses revealed the formation, high distribution and strongbonding of sodium acetate crystals within the concrete’s micropores

BrAPI-an application programming interface for plant breeding applications

Motivation: Modern genomic breeding methods rely heavily on very large amounts of phenotyping and genotyping data, presenting new challenges in effective data management and integration. Recently, the size and complexity of datasets have increased significantly, with the result that data are often stored on multiple systems. As analyses of interest increasingly require aggregation of datasets from diverse sources, data exchange between disparate systems becomes a challenge. Results: To facilitate interoperability among breeding applications, we present the public plant Breeding Application Programming Interface (BrAPI). BrAPI is a standardized web service API specification. The development of BrAPI is a collaborative, community-based initiative involving a growing global community of over a hundred participants representing several dozen institutions and companies. Development of such a standard is recognized as critical to a number of important large breeding system initiatives as a foundational technology. The focus of the first version of the API is on providing services for connecting systems and retrieving basic breeding data including germplasm, study, observation, and marker data. A number of BrAPI-enabled applications, termed BrAPPs, have been written, that take advantage of the emerging support of BrAPI by many databases