IN SILICO ANTIMALARIAL TARGET SELECTION CONSERVED IN FOUR PLASMODIUM SPECIES

Objectives: The need for new antimalarials drugs and drug targets is pertinent due to the emergence of drug resistant strains of the parasites. Improper target selection has resulted in therapeutic failure. The genomic/post genomic era has made possible the deciphering of the 3D crystal structures of proteins and DNA which are drug targets and are deposited in the protein data bank. Methods: Novel antimalarial targets obtained from evolutionary conserved short sequence motifs are utilised and are essential in transcription processes in the parasite. The motifs TGCATGCA, GTGCAC and GTGCGTGC were curated from experimental work, validated and analysed via phylogenomics genomics and comparative genomics. PlasmoDB blastn was applied to determine their similarity in Plasmodium vivax, knowlesi, Ovale and yoeli. The complete genome of Plasmodium falciparum vivax, knowlesi, Ovale and yoeli was downloaded from the plasmoDB and their positions determined. Results: The targets are essential, conserved in rodent and mammalian species via phylogenomics with percentage identity and similarity greater than 80%, have no similar genes in the same genome and also found to be selective in the parasites vis-à-vis the Homo sapiens via comparative genomics with 0% identity and similarity in the human genome. Conclusion: The targets reveal at the molecular and biochemical level, the vulnerable regions in the parasite while safe in human hence their choices in subsequent rationale drug discovery and design protocols.                         Peer Review History: Received: 18 July 2020; Revised: 1 October; Accepted: 12 October, Available online: 15 November 2020 Academic Editor: Dr. Sally A. El-Zahaby, Pharos University in Alexandria, Egypt, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency. Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Tamer ELHABIBI, ERU University, Egypt, [email protected] Dr. Soroush Sardari, Biotech Pasteur Institute of Iran, Tehran, Iran, [email protected] Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITOR

Development of a Rapid Chemical Identification System (RCIS) for the Detection of Fraudulently Labelled 5-nitroimidazole Products

Purpose: A simple, reliable and rapid chemical identification system (RCIS) consisting of three colour reactions based on the functional groups in the molecule and two TLC methods was developed for preliminary detection of the 5–nitroimidazole drugs.Methods: Three members of this group of drugs (tablet form) available in the Nigerian market and labelled MA and MB for metronidazole, T A and TB for tinidazole and S for secnidazole, were used. The extraction of the active ingredient from the solid dosage form was performed using acetone. The reaction of the extracted drug with zinc and 1M hydrochloric acid at 100 oC converted the nitroimidazole group to a characteristic primary aromatic amine. TLC methods A and B were carried out on GF254 plates (5cm x 10cm) to further identify the individual members of the group. TLC method A with mobile phase consisting of acetone, ethyl acetate and ammonia (100:5:1) and method B with mobile phase consisting of acetone, chloroform and ammonia (100:15:1) were developed for the identification.Results: The aromatic character of 5-nitroimidazole was highlighted in nitric acid when combined with sulphuric acid resulting in an orange colour. 40% sodium hydroxide gave the alkali-induced characteristic orange colour of aromatic amino compounds. All the samples of the various brands gave characteristic colours that distinguished the compounds of the 5-nitroimidazole group as primary or secondary nitroimidazole compounds.Conclusion: Using the developed method, fraudulently labelled product 5-nitroimidazole antiprotozoal and antibacterial agents can now be detected in approx. 40 min with limited reagents and a simple TLCtechnique. The method is rugged, simple, and should be particularly handy for use in detecting substandard products of the drug in the drug distribution chain where sophisticated equipment are often not available.Keywords: 5–nitroimidazole; Fraudulently labeled; Chemical identification system; Antiprotozoal; Antibacterial

IN SILICO IDENTIFICATION OF TARGET PALINDROMIC GENES AS POTENTIAL DRUG TARGETS IN BREAST CANCER THERAPY

Objectives: Breast cancer (BC) is the most common cancer worldwide prevalent among women with more than one million cases and is second only to lung cancer. Methods: The identification of the sequences based on the unique tetramers GCAC, GTCA were selected from experimental work. The16 base pair DNA regulatory sequences of which the motifs area part of containing these motif in genes implicated in cancer CAGE1 (AAGCTGTCATTA), BRCA1(GACTGAGTCAA), ABCB1(CTCTAAGTCAT), ABCB5 (GATATGTTAAAGC) and ABI1(CTTCTGGGAA)  were then selected as novel putative targets in breast cancer therapy based on their selectivity on the BC oncogenes which are not found in the normal human genome 1-23 and the sex chromosomes X and Y were obtained via computational analysis. Results: The single copy base pairs which will be potential drug targets as anticancer drugs were finally obtained as CTGTTATGACTGAGTCAA, CAGE1 with the 17 base pairs CATAAAAGC TGTCATTA and ABCB1 TTGCCAA CTCTAAGT CAT. Conclusion: It is Possible that the in silico discovery of putative anti breast cancer targets of importance in the genome. Peer Review History: Received 18 July 2020; Revised 25 September; Accepted 12 October, Available online 15 November 2020 Academic Editor: Prof. Kumud Upadhyaya, Kumaon University, Nainital, UK, India, [email protected] UJPR follows the most transparent and toughest ‘Advanced OPEN peer review’ system. The identity of the authors and, reviewers will be known to each other. This transparent process will help to eradicate any possible malicious/purposeful interference by any person (publishing staff, reviewer, editor, author, etc) during peer review. As a result of this unique system, all reviewers will get their due recognition and respect, once their names are published in the papers. We expect that, by publishing peer review reports with published papers, will be helpful to many authors for drafting their article according to the specifications. Auhors will remove any error of their article and they will improve their article(s) according to the previous reports displayed with published article(s). The main purpose of it is ‘to improve the quality of a candidate manuscript’. Our reviewers check the ‘strength and weakness of a manuscript honestly’. There will increase in the perfection, and transparency.                                                    Received file:                Reviewer's Comments: Average Peer review marks at initial stage: 5.5/10 Average Peer review marks at publication stage: 7.0/10 Reviewer(s) detail: Dr. Nkechi Obiofu Ezenobi, University of Port Harcourt, Nigeria, [email protected] Shahin Gavanji, World Academy of Medical Sciences, Iran,  [email protected] Similar Articles: IN SILICO LIGAND-BASED 2D PHARMACOPHORE GENERATION FOR H+/K+ ATPASE INHIBITOR

RUSSO-UKRAINIAN WAR: CAUSES AND AFTERMATHS

The international system has been enjoying relative peace almost immediately after the end of the cold war. However, recent development especially among the so-called ‘super powers’ in Europe and terrorism as well as insurgency has been considered has a threatening factor for the relative peace enjoyed by mankind. There has always been an unhealthy relation between Russia and Ukraine since the days of the defunct Soviet Union. The recent unfortunate Russian-Ukrainian war which has revived the bad blood relationship between the two warring nations has undoubtedly attracted wider global attention for the implications of the recent development are better imagined than seen or felt directly or indirectly. Since the break-up of the USSR, political tensions between the two neighbouring states-Ukraine and Russia-have continued on many issues. The conflict that rears its ugly head in that part of the world had its roots at the very outset of the post-Cold War era. It is against this backdrop that the paper examines the current crisis between Russia and Ukraine. It discusses the remote and immediate causes of the war. Attempt would be equally made to x-ray the implications of the war as it is likely to affect the international system and the peaceful co-existence of mankind especially when most countries of the world are grappling with the negative effects of COVID-19. Finally, the paper will be concluded with recommendations. Primary and secondary sources were used in the collection, collation and interpretation of data

PHYSICOCHEMICAL PROPERTIES OF SOME PAEDIATRIC AND ADULT PRODUCTS OF DIHYDROARTEMISININ-PIPERAQUINE ANTIMALARIAL MARKETED IN NIGERIA

The quality indices of dihydroartemisinin–piperaquine (DP) pediatric and adult (DPP and DPA) formulations of antimalarial were assessed. Moisture content, viscosity, total solid for four (DPP) products along with weight uniformity, tablet hardness, friability, disintegration and dissolution for six (DPA) products, were determined. Assay of chemical content was performed using reverse phase high pressure liquid chromatographic (RP-HPLC) with Zorbax Eclipse XDB C8 column (150 x 4.6 mm, 4.6 µm)), UV detection at 220 nm and flow rate of 0.7 mL/min. Acetonitrile: 10 mM ammonium acetate (70:30%, v/v) and tinidazole served as mobile phase and internal standard, respectively. Statistical analysis of data was performed using Minitab statistical software with one-way analysis of variance comparing the parameters among the formulations and confidence interval set at 95%. DPP products showed pH and moisture content within 3.19 to 4.65 units and 2.6 to 4.4%, respectively. Total solid and viscosity values were within 86.2 to 97.2% and 78.5 to 125.8 mPa.s, respectively. DPA products had comparable and satisfactory weight uniformity, hardness, friability and disintegration tests results except for DPA5 and DPA6 which failed the weight uniformity tests featuring tablets with deviation from the mean above 5%. All DPP products passed chemical content test with values within 92.65 to 101.22% while DPA2, DPA4 and DPA5 failed. All DPA products showed poor dissolution characteristics with C40 values below 60% and T70 values above 70 min. All DP products showed varying physicochemical properties that may give differing drug performance in vivo. Key words: Dihydroartemisinin-piperaquine, antimalarial, physicochemical properties, Chemical content, biopharmaceutical indices

Incubation period of typhoidal salmonellosis : a systematic review and meta-analysis of outbreaks and experimental studies occurring over the last century

Background Salmonella Typhi is a human pathogen that causes typhoid fever. It is a major cause of morbidity and mortality in developing countries and is responsible for several outbreaks in developed countries. Studying certain parameters of the pathogen, such as the incubation period, provides a better understanding of its pathophysiology and its characteristics within a population. Outbreak investigations and human experimental studies provide an avenue to study these relevant parameters. Methods In this study, the authors have undertaken a systematic review of outbreak investigation reports and experimental studies, extracted reported data, tested for heterogeneity, identified subgroups of studies with limited evidence of heterogeneity between them and identified factors that may contribute to the distribution of incubation period. Following identification of relevant studies, we extracted both raw and summary incubation data. We tested for heterogeneity by deriving the value of I2 and conducting a KS-test to compare the distribution between studies. We performed a linear regression analysis to identify the factors associated with incubation period and using the resulting p-values from the KS-test, we conducted a hierarchical cluster analysis to classify studies with limited evidence of heterogeneity into subgroups. Results We identified thirteen studies to be included in the review and extracted raw incubation period data from eleven. The value of I2 was 84% and the proportion of KS test p-values that were less than 0.05 was 63.6% indicating high heterogeneity not due to chance. We identified vaccine history and attack rates as factors that may be associated with incubation period, although these were not significant in the multivariable analysis (p-value: 0.1). From the hierarchical clustering analysis, we classified the studies into five subgroups. The mean incubation period of the subgroups ranged from 9.7 days to 21.2 days. Outbreaks reporting cases with previous vaccination history were clustered in a single subgroup and reported the longest incubation period. Conclusions We identified attack rate and previous vaccination as possible associating factors, however further work involving analyses of individual patient data and developing mathematical models is needed to confirm these as well as examine additional factors that have not been included in our study

Within-host mathematical modelling of the incubation period of Salmonella Typhi

Mechanistic mathematical models are often employed to understand the dynamics of infectious diseases within a population or within a host. They provide estimates that may not be otherwise available. We have developed a within-host mathematical model in order to understand how the pathophysiology of Salmonella Typhi contributes to its incubation period. The model describes the process of infection from ingestion to the onset of clinical illness using a set of ordinary differential equations. The model was parametrized using estimated values from human and mouse experimental studies and the incubation period was estimated as 9.6 days. A sensitivity analysis was also conducted to identify the parameters that most affect the derived incubation period. The migration of bacteria to the caecal lymph node was observed as a major bottle neck for infection. The sensitivity analysis indicated the growth rate of bacteria in late phase systemic infection and the net population of bacteria in the colon as parameters that most influence the incubation period. We have shown in this study how mathematical models aid in the understanding of biological processes and can be used in estimating parameters of infectious diseases

Taste and safety : is the exceptional cuisine offered by high end restaurants paralleled by high standards of food safety?

Introduction: Restaurant guides such as the Good Food Guide Top 50 create a hierarchy focussing on taste and sophistication. Safety is not explicitly included. We used restaurant associated outbreaks to assess evidence for safety. Methods: All foodborne disease outbreaks in England reported to the national database from 2000 to 2014 were used to compare the Top 50 restaurants (2015) to other registered food businesses using the Public Health England (PHE) outbreak database. Health Protection Teams were also contacted to identify any outbreaks not reported to the national database. Among Good Food Guide Top 50 restaurants, regression analysis estimated the association between outbreak occurrence and position on the list. Results: Four outbreaks were reported to the PHE national outbreak database among the Top 50 giving a rate 39 times higher (95% CI 14.5–103.2) than other registered food businesses. Eight outbreaks among the 44 English restaurants in the Top 50 were identified by direct contact with local Health Protection Teams. For every ten places higher ranked, Top 50 restaurants were 66% more likely to have an outbreak (Odds Ratio 1.66, 95% CI 0.89–3.13). Discussion: Top 50 restaurants were substantially more likely to have had reported outbreaks from 2000-2014 than other food premises, and there was a trend for higher rating position to be associated with higher probability of reported outbreaks. Our findings, that eating at some of these restaurants may pose an increased risk to health compared to other dining out, raises the question of whether food guides should consider aspects of food safety alongside the clearly important complementary focus on taste and other aspects of the dining experience

Factors influencing the time between onset of illness and specimen collection in the diagnosis of non-pregnancy associated listeriosis in England and Wales

Background Listeriosis is an opportunistic bacterial infection caused by Listeria monocytogenes and predominantly affects people who are immunocompromised. Due to its severity and the population at risk, prompt clinical diagnosis and treatment of listeriosis is essential. A major step to making a clinical diagnosis is the collection of the appropriate specimen(s) for testing. This study explores factors that may influence the time between onset of illness and collection of specimen in order to inform clinical policy and develop necessary interventions. Methods Enhanced surveillance data on non-pregnancy associated listeriosis in England and Wales between 2004 and 2013 were collected and analysed. The difference in days between onset of symptoms and collection of specimen was calculated and factors influencing the time difference were identified using a gamma regression model. Results The median number of days between onset of symptoms and collection of specimen was two days with 27.1 % of cases reporting one day between onset of symptoms and collection of specimen and 18.8 % of cases reporting more than seven days before collection of specimen. The median number of days between onset of symptoms and collection of specimen was shorter for cases infected with Listeria monocytogenes serogroup 1/2b (one day) and cases with an underlying condition (one day) compared with cases infected with serotype 4 (two days) and cases without underlying conditions (two days). Conclusions Our study has shown that Listeria monocytogenes serotype and the presence of an underlying condition may influence the time between onset of symptoms and collection of specimen