In silico characterization of plasmodial transketolases as potential malaria drug target

Expected release date-April 201

In silico characterization of plasmodial transketolases as potential malaria drug target

Expected release date-April 201

Religious Pluralism in Ghana: Using the Accommodative Nature of African Indigenous Religion (AIR) as a Source for Religious Tolerance and Peaceful Coexistence

This article deploys the accommodative nature of African Indigenous Religion (AIR) as a reflective tool in Ghana’s religious pluralistic context. This paper argues that the accommodative nature of AIR which has made scholars argue for its singularity can serve as a tool which would promote religious tolerance and peaceful coexistence in Ghana. The findings of the research demonstrated that though there is a level of religious tolerance and peaceful coexistence among various religious groups in Ghana, there is still more room for improvement, thus the proposal of this model as a response

Real exchange rate misalignment and macroeconomic implications: Recent evidence from Ghana

We evaluate the degree of real exchange rate (REER)  misalignment and its macroeconomic implications for the  Ghanaian economy using quarterly data (2000Q1-2015Q3). Our results uncovered a clear misalignment of the actual REER from its equilibrium level throughout the sample period, although the REER was close to its equilibrium level at the end of 2012. The study also revealed a weak positive undervaluation-economic growth nexus for Ghana. Overvaluation was observed to exert disinflationary pressures, while undervaluation tends to increase inflationary pressures in Ghana. The study thus suggests that the use of REER undervaluation as a deliberate industrial policy instrument for sustained economic growth may be  counterproductive in the context of Ghana, as such policy may potentially undermine price stability objective of the central bank.Keywords: Equilibrium Exchange Rate; Misalignment;Ghana

Low birth weight among adolescents at Cape Coast Metropolitan Hospital of Ghana

Background: Few studies have focused on low birth weight among adolescents. This study determines the incidence and factors associated with low birth weight (LBW) (weight at birth of less than 2,500 grams) among adolescents (aged <20 years) and how they differ from those in adult mothers (aged ≥20 years).Methods: The records of 768 deliveries at a hospital in Ghana from August 2014 to March 2015 were analyzed. Frequencies and percentages were generated. Bivariate relationships between maternal and neonatal characteristics and LBW were assessed using Chi-squared test. Multivariate logistic regression was used to evaluate the association between maternal age (being adolescent) and LBW. Odds ratios with 95% confidence interval were generated, and p < 0.05 was considered significant.Results: The incidence of LBW among adolescents was 14.3% and this was higher than the one among babies born to adult mothers (14.3 % vs. 7.4 %, p <0.013). Adolescent mothers were twice as likely to give birth to babies with LBW compared to adult mothers (OR 2.22; 95% CI: 1.16 - 4.25). Preterm birth was significantly associated with LBW among adolescent and adult mothers.Conclusions: Adolescents are at a higher risk of giving birth to babies of LBW than adults. Factors predicting LBW may not be different for adolescent and adult mothers. Interventions for prevention of negative sexual health outcomes should focus on adolescents

Prevalence of red blood cell antibodies among transfused patients at Komfo Anokye teaching (Kath) hospital, Ghana

Red blood cell (RBC) alloimmunisation is a common problem in transfused patients because of the possibility of haemolytic reaction and limited availability of compatible blood. In highincome countries, pre-transfusion antibody screening is performed routinely. In Ghana, patients are transfused with ABO Rh ‘D’ compatible blood without screening for immune antibodies. We therefore studied the prevalence and specificities of RBC antibodies in transfused patients at Komfo Anokye Teaching hospital, Ghana. The study was cross-sectional, involving previously transfused patients who required another transfusion. Participants’ basic data on demography and transfusion history were recorded. Blood samples were screened and subsequently typed for RBC antibodies using a column gel agglutination test. A total of 106 transfused patients, 52 male and 54 females were enrolled. The patients had previously received a median of 4 RBC units (range 1-14). Of these, ten patients (9.4%) had 11 RBC alloantibodies, whose specificities were 2 anti-K; 2 anti-C; one each of anti-D, -E, -M, and -S; and 3 were pan-reactive. The number of transfusion episodes was significantly associated with the rate of alloimmunisation (p=0.000). In conclusion the overall alloimmunisation rate in the study was 9.4% and this was significantly associated with increasing number of transfusion episodes. Antibodies were mainly directed against antigens in the Rhesus system and K antigen. We recommend that antibody screening be incorporated into routine pre-transfusion testing procedures in Ghana. Keywords: Alloimmunisation, multi transfusion, Alloantibod

Household cost of chronic kidney disease care among patients presenting at Komfo Anokye Teaching Hospital, Ghana

Background: Chronic kidney disease (CKD) has a major effect on global health, both as a direct cause of morbidity and mortality and as a risk factor for cardiovascular disease. This study was carried out to determine the household cost of CKD care among patients receiving treatment at a tertiary healthcare facility in Ghana. Methods: This was a cross-sectional study conducted over a period of three months. The estimated household cost of CKD care was made up of direct and indirect cost of treating the condition. The direct cost was divided into direct medical cost and direct non-medical cost. The direct medical cost included cost of medication, outpatient consultations, cost of dialysis, diagnostic investigations (including laboratory investigations), and ultrasound and computed tomography requests. The direct non-medical cost included cost of feeding and transportation. The indirect cost was based on the total time lost to productivity. Results: A total of 224 patients were included in the study. The mean ±SD age of the patients was 49.62 ±15.37 years. The overall average monthly cost of CKD care for the 224 patients was GH₵ (US$) 1,121.42 (198.63), making up of 87.70% direct cost and 12.30% indirect cost. The cost incurred by CKD patients on dialysis was significantly higher and almost four times higher than that of the end stage non-dialysis CKD patients

Global Analysis of Plasmodium falciparum Dihydropteroate Synthase Variants Associated with Sulfadoxine Resistance Reveals Variant Distribution and Mechanisms of Resistance: A Computational-Based Study

The continual rise in sulfadoxine (SDX) resistance affects the therapeutic efficacy of sulfadoxine-pyrimethamine; therefore, careful monitoring will help guide its prolonged usage. Mutations in Plasmodium falciparum dihydropteroate synthase (Pfdhps) are being surveilled, based on their link with SDX resistance. However, there is a lack of continuous analyses and data on the potential effect of molecular markers on the Pfdhps structure and function. This study explored single-nucleotide polymorphisms (SNPs) in Pfdhps that were isolated in Africa and other countries, highlighting the regional distribution and its link with structure. In total, 6336 genomic sequences from 13 countries were subjected to SNPs, haplotypes, and structure-based analyses. The SNP analysis revealed that the key SDX resistance marker, A437G, was nearing fixation in all countries, peaking in Malawi. The mutation A613S was rare except in isolates from the Democratic Republic of Congo and Malawi. Molecular docking revealed a general loss of interactions when comparing mutant proteins to the wild-type protein. During MD simulations, SDX was released from the active site in mutants A581G and A613S before the end of run-time, whereas an unstable binding of SDX to mutant A613S and haplotype A437A/A581G/A613S was observed. Conformational changes in mutant A581G and the haplotypes A581G/A613S, A437G/A581G, and A437G/A581G/A613S were seen. The radius of gyration revealed an unfolding behavior for the A613S, K540E/A581G, and A437G/A581G systems. Overall, tracking such mutations by the continuous analysis of Pfdhps SNPs is encouraged. SNPs on the Pfdhps structure may cause protein&ndash;drug function loss, which could affect the applicability of SDX in preventing malaria in pregnant women and children

NOP RECEPTOR TRANSDUCEROME: INSIGHTS INTO BIASED AGONISM

reservedI recettori accoppiati alle proteine G (GPCR) sono la più grande famiglia di recettori espressi sulla superficie cellulare e svolgono ruoli critici in una varietà di attività fisiologiche. I GPCR mediano i loro effetti preferenzialmente attivando le proteine G eterotrimeriche. Le proteine G sono suddivise in quattro famiglie (Gi/o, Gs, Gq/11 e G12/13) che modulano i livelli di determinati secondi messageri (come il cAMP, il calcio, ecc) e l’attivazione di altri effettori (come Rho A). Il recettore NOP (recettore attivo dal neuropeptide endogeno nocicettina/orfanina FQ (N/OFQ)) è il membro più recentemente identificato della famiglia dei recettori oppioidi. Il recettore NOP si trova in importanti substrati neuronali che modulano il dolore e la ricompensa. Inoltre, il recettore NOP mostra una distribuzione ubiquitaria che consente a N/OFQ di modulare una varietà di processi fisiologici (sia centralmente che perifericamente). Di conseguenza, il recettore NOP ha attirato considerevole attenzione come possibile bersaglio per lo sviluppo di ligandi innovativi in una varietà di condizioni patologiche. I GPCR possono esistere in diverse conformazioni attive, che possono portare, tramite l’accoppiamento a diversi effettori, alla modulazione di diverse vie trasduzionali. L’agonismo “bias” è una proprietà dei ligandi per i GPCR che implica come i diversi agonisti siano in grado di modulare selettivamente specifiche conformazioni del recettore, portando all’attivazione selettiva di determinate vie di segnalazione rispetto ad altre. In questa tesi, abbiamo utilizzato un approccio innovativo per studiare l’attivazione del recettore NOP umano. In particolare, per la sua propensione di attivare le principali proteine G di tipo inibitorio (ossia Gi1, Gi2, Gi3, GoA, GoB). Questo approccio, chiamato “Trupath”, si basa sul trasferimento di energia di risonanza bioluminescente (BRET) ed è in grado di misurare l’attivazione/dissociazione di queste proteine G eterotrimeriche. Nei nostri esperimenti, abbiamo impiegato, insieme a N/OFQ, un panello di 20 diversi ligandi del recettore NOP di natura diversa (peptidici e non peptidici) e alcuni di questi con diversi gradi di “bias”. N/OFQ ha attivato tutte le proteine G studiate con un alto valore di potenza compreso tra 0.1 e 1 nM. Inoltre, la maggiore parte dei composti testati, se confrontati agli effetti di N/OFQ hanno mostrato un profilo farmacologico simile tra i diversi trasduttori (non “biased”) e in linea con quanto osservato in set di dati precedentemente riportati. Le osservazioni effettuate in questa tesi sono di notevole importanza per approfondire la comprensione del meccanismo di attivazione del recettore NOP e, in una prospettiva futura, per sviluppare farmaci specifici per i vari trasduttori.G protein-coupled receptors (GPCRs) are the largest family of cell surface receptors known to serve critical roles in a variety of physiological activities. GPCRs mediate their effect preferentially by triggering heterotrimeric G proteins. G proteins are subdivided into four families (i.e., Gi/o, Gs, Gq/11, and G12/13) that modulate the levels of certain second messengers (e.g., cAMP, calcium, etc.) and the activation of other effectors (e.g., Rho A). The NOP receptor (a receptor activated by the endogenous neuropeptide nociceptin/orphanin FQ (N/OFQ)) is the most recently identified member of the opioid receptor family. The NOP receptor is found in important neuronal substrates that modulate pain and reward. In addition, NOP receptors display a ubiquitous distribution, allowing N/OFQ to modulate a variety of physiological processes (centrally and peripherally). As a result, the NOP receptor has received considerable attention as a possible target for the development of ligands with therapeutic promise in a variety of pathological situations. GPCRs can exist in multiple active conformations, leading in turn to different downstream effects and coupling. Biased agonism is a unique paradigm in GPCR signaling that illustrates how various ligands preferentially maintain certain receptor conformations, resulting in the selective activation of certain signaling pathways over others. In this thesis, we aimed to apply a truly innovative approach to study the activation by the (human) NOP receptor of the most relevant inhibitory G proteins (i.e., Gi1, Gi2, Gi3, GoA, and GoB). This approach (i.e., named “trupath”) is based on a bioluminescence resonance energy transfer (BRET) approach allowing to measure the activation/dissociation of these heterotrimeric G proteins. We employed, together with N/OFQ, a panel of 20 different NOP ligands of different natures (peptide and non-peptide), some of which already exhibit a variety of “bias” degrees. N/OFQ displayed with all the G proteins a high value of potency ranging 0.1-1 nM. In addition, most of the compounds tested, when compared to N/OFQ, showed a similar profile across all transducers, and displayed a pharmacological profile close to what observed in previously reported datasets. Observations carried out in this thesis will be very informative for proceeding into a deeper understanding of the mechanism of NOP activation, and in a future perspective, to realize transducer specific medicines