Current development of 1,2,3-triazole derived potential antimalarial scaffolds: Structure- activity relationship (SAR) and bioactive compounds.

Malaria is among one of the most devastating and deadliest parasitic disease in the world claiming millions of lives every year around the globe. It is a mosquito-borne infectious disease caused by various species of the parasitic protozoan of the genus Plasmodium. The indiscriminate exploitation of the clinically used antimalarial drugs led to the development of various drug-resistant and multidrug-resistant strains of plasmodium which severely reduces the therapeutic effectiveness of most frontline medicines. Therefore, there is urgent need to develop novel structural classes of antimalarial agents acting with unique mechanism of action(s). In this context, design and development of hybrid molecules containing pharmacophoric features of different lead molecules in a single entity represents a unique strategy for the development of next-generation antimalarial drugs. Research efforts by the scientific community over the past few years has led to the identification and development of several heterocyclic small molecules as antimalarial agents with high potency, less toxicity and desired efficacy. Triazole derivatives have become indispensable units in the medicinal chemistry due to their diverse spectrum of biological profiles and many triazole based hybrids and conjugates have demonstrated potential in vitro and in vivo antimalarial activities. The manuscript compiled recent developments in the medicinal chemistry of triazole based small heterocyclic molecules as antimalarial agents and discusses various reported biologically active compounds to lay the groundwork for the rationale design and discovery of triazole based antimalarial compounds. The article emphasised on biological activities, structure activity relationships, and molecular docking studies of various triazole based hybrids with heterocycles such as quinoline, artemisinins, naphthyl, naphthoquinone, etc. as potential antimalarial agents which could act on the dual stage and multi stage of the parasitic life cycle.

Spotlight on Exosomal Non-Coding RNAs in Breast Cancer: An In Silico Analysis to Identify Potential lncRNA/circRNA-miRNA-Target Axis.

Breast cancer (BC) has recently become the most common cancer type worldwide, with metastatic disease being the main reason for disease mortality. This has brought about strategies for early detection, especially the utilization of minimally invasive biomarkers found in various bodily fluids. Exosomes have been proposed as novel extracellular vesicles, readily detectable in bodily fluids, secreted from BC-cells or BC-tumor microenvironment cells, and capable of conferring cellular signals over long distances via various cargo molecules. This cargo is composed of different biomolecules, among which are the novel non-coding genome products, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and the recently discovered circular RNA (circRNA), all of which were found to be implicated in BC pathology. In this review, the diverse roles of the ncRNA cargo of BC-derived exosomes will be discussed, shedding light on their primarily oncogenic and additionally tumor suppressor roles at different levels of BC tumor progression, and drug sensitivity/resistance, along with presenting their diagnostic, prognostic, and predictive biomarker potential. Finally, benefiting from the miRNA sponging mechanism of action of lncRNAs and circRNAs, we established an experimentally validated breast cancer exosomal non-coding RNAs-regulated target gene axis from already published exosomal ncRNAs in BC. The resulting genes, pathways, gene ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis could be a starting point to better understand BC and may pave the way for the development of novel diagnostic and prognostic biomarkers and therapeutics.

A Signature of Four Circulating microRNAs as Potential Biomarkers for Diagnosing Early-Stage Breast Cancer.

Breast cancer (BC) is the most predominant type of cancer among women. The aim of this study is to find new biomarkers that can help in early detection of BC, especially for those who are too young to be screened using mammography as per guidelines. Using microRNA microarray, we previously showed dysregulation of 74 microRNAs in tumors from early BC patients as compared with normal adjacent tissues, which we were interested in studying in blood circulation. In this study, we investigated the expression of 12 microRNA (miR-21/miR-155/miR-23a/miR-130a/miR-145/miR-425-5p/miR-139-5p/miR-451/miR-195/miR-125b/miR-100, and miR-182) in the plasma of 41 newly diagnosed Lebanese BC patients with early invasive ductal carcinoma as compared with 32 healthy controls. Total RNA was extracted from plasma, and expression levels of miRNA of interest were measured using RT-qPCR followed by statistical analysis; miR-21, miR-155, miR-23a, miR-130a, miR-145, miR-425-5p, and miR-139-5p were significantly upregulated and miR-451 was significantly downregulated, in the plasma of BC patients as compared with healthy controls. The positively correlated miR-23a, miR-21, and miR-130a had a high diagnostic accuracy (86%). Importantly, the combination of miR-145/miR-425-5p/miR-139-5p/miR-130a scored the highest diagnostic accuracy of 95% with AUC = 0.97 (sensitivity 97% and specificity 91%). MicroRNAs are promising non-invasive diagnostic biomarkers for early-stage BC with the panel of miR-145/miR-425-5p/miR-139-5p/miR-130a having the highest diagnostic accuracy.

Operative management of non-iatrogenic pediatric and adolescence peripheral arterial trauma: An experience from a resource challenged setting.

OBJECTIVES: To evaluates the management and outcome of non-iatrogenic pediatric and adolescence extremity arterial injuries in a resource-challenged setting. METHODS: A retrospective study of the surgical management for non-iatrogenic extremity arterial trauma in pediatric and adolescence during the period from January 2008 to December 2015. This study was performed in two different countries at tertiary referral university and teaching hospitals having a specialized emergency and trauma centers. A thorough study of each patient record was collected from these centers including, the original demographic data and their clinical presentations. Operative data of each patient was also reported. RESULTS: During the 8-year period of the study, 149 pediatric and adolescent extremity arterial trauma patients were treated. They were 93.3% male, and 6.7% female, respectively. The age ranged from 2 to 18 years with a mean of 10.25 ± 4.05 years. Lower extremity arterial trauma was recorded in 51%, while 49% were having upper extremity injuries. Primary repair with end-to-end vascular anastomosis was performed in 51.7%, while an interposition reversed saphenous vein graft was performed in 48.3%. The operative procedures were performed by an experienced vascular surgeon and well-trained pediatric surgeons and general surgeons. Pseudoaneurysms was recorded in 9% of cases. Fasciotomy was performed in 15% of cases. CONCLUSION: Treatment of pediatric and adolescent extremity arterial injuries with primary end-to-end vascular anastomoses or with the use of an interposition reversed saphenous vein graft is a reliable, feasible, and more cost-effectiveness technique with good results. Moreover, it should be adopted for all vascular trauma patients, whenever possible.

Molecular characterization of fowl aviadenoviruses species D and E associated with inclusion body hepatitis in chickens and falcons indicates possible cross-species transmission.

During the period from 2015 to 2017, frequent outbreaks of inclusion body hepatitis (IBH) were observed in broiler chickens and falcons in Saudi Arabia. Fifty samples were collected from both species. The histopathological examination and polymerase chain reaction confirmed the IBH infection in eight samples (five samples from chickens and three samples from falcons). The genomic sequence and phylogenetic analysis based on nucleotide and amino acid sequences of Saudi strains, reference fowl aviadenoviruses (FAdVs) and field viruses available in Genbank revealed that all investigated FAdVs clustered into FAdV-2 (species D) and FAdV-6 (species E). The host-dependent characterization revealed that falcon origin strains showed low identity (∼35%) with falcon adenoviruses isolated from USA, which clustered into a separate group. The identification of FAdV-D and FAdV-E in diseased falcons and chickens indicates cross-species transmission although falcons and chickens are phylogenetically different. The control of IBH infection in falcons and chickens should be based on the separation of carriers and susceptible chickens as well as falcons to prevent cross-species contact. Vaccination is an important method for prevention of IBH. The characterization of newly emerging FAdV strains provides valuable information for the development of an efficacious control strategy based on the molecular structure of current circulating FAdV strains in different species of birds.

Role of plasma-rich fibrin in oral surgery.

Platelet-rich fibrin (PRF) is a fibrin meshwork, in which platelet cytokines, growth factors, and cells are entrapped and discharged after a period and can serve as a resorbable film. PRF is the next generation of platelet concentrates equipped to improve arrangement without biochemical blood handling; PRF is an evolution of the fibrin adhesive, which is widely used in the oral surgery. The guidelines of this innovation depend on concentrating platelets and growth factors in a plasma medium, and initiating them in a fibrin gel, keeping in mind the end goal to enhance the healing of wounds. Maxillary bone loss requires numerous regenerative techniques: as a supplement to the procedures of tissue regeneration, a platelet concentrate called PRF was tested for the 1st time in France by Dr. Choukroun. This article enriches the benefits and role of plasma-rich fibrin in oral surgery. Platelet-concentrate fibrin is an evolution of the fibrin glue, which is widely used in the oral surgery.

Embolized amplatzer duct occluder to aorta: Retrieval technique.

A 4-year-old girl had an Amplatzer duct occluder embolized to the descending aorta immediately after closure of patent ductus arteriosus: a novel technique of retrieval.

Factors affecting health related quality of life of rectal cancer patients undergoing surgery.

Maintaining quality of life (QOL) is one of the important aims of cancer treatment. Quality of life of a cancer patient is affected by various factors, which may be disease related, patient related, or treatment related. To study changes in health-related quality of life (HRQOL) brought about by treatment of rectal cancer and factors affecting the changes using Malayalam translation of FACT-C (Functional Assessment of Cancer Therapy-Colorectal) Questionnaire. Also to detect the minimally important clinical changes (MICC) in health-related quality of life of patients with carcinoma rectum, who have undergone surgery. Forty-five patients diagnosed with carcinoma rectum, who have undergone curative surgery, were studied. HRQOL was assessed at baseline 2 weeks after surgery and 3 months after surgery. The changes in scores were correlated with various demographic factors like age, sex, marital status, number of children, number of married children, and education and occupation of the patient and spouse. Also the treatment-related factors like presence of stoma, presence of morbidity, previous treatment, stage of disease, and administration of chemotherapy before and after surgery were correlated. All the subscales of FACT-C tool, except emotional well-being, were significantly reduced 2 weeks after surgery and increased slightly above pre-treatment level 3 months after surgery. The Chronbach α values were 0.88, 0.89 and 0.86 on three occasions, respectively, establishing internal validity of the test. Baseline HRQOL scores were better in males compared to females. Among the various subscales, the drops in SWB, FWB, FACT-G, total Score and TOI were significant (P < .05).There were no significant differences in scores between patients who have undergone open surgery and minimally invasive surgery or patients who had permanent colostomy versus no colostomy. The HRQOL scores after surgery reduced 2 weeks after surgery and improved above pre-surgical levels 3 months after surgery. The approach of surgery (minimally invasive versus open) or presence or absence of permanent colostomy didn't make any significant change in HRQOL. But since the sample size of the study was small, we need further larger studies to arrive at definite conclusions.

Oral Lesion as the first Clinical Presentation in Sarcoidosis: A Case Report.

Sarcoidosis is a common multi-system disease characterized histolopathologically by the formation of non-caseating granulomas in the affected tissues. The oral involvement of sarcoidosis is relatively rare with less than 70 reported cases in literature while an oral lesion as the initial presenting sign is even less common. Oral lesions of sarcoidosis may mimic the lesions of other serious systemic diseases including Crohn's disease and tuberculosis as well as lesions localized to the orofacial region such as orofacial granulomatosis. This report presents a case of non-progressive sarcoidosis where the initial presenting symptom was a lesion in the buccal vestibule attached to the gingivae. A brief review of the pathology and clinical features is also presented.

[A critical view of Arabic curriculum as a requirement for medical schools, Gezira University].

We compared the present Arabic syllabus used in Gezira University Medical School with previous ones. We also surveyed students and Arabic professors in medical sciences on their views on the content and teaching/evaluation procedures and how these contributed to students' understanding of the medical science syllabus. The current syllabus was designed to provide students with Arabic language skills with particular reference to scientific language. The students' opinions differed regarding their understanding of clinical medicine and their interaction with patients and also the benefits to them of research procedures and reporting. The professors considered the syllabus was adequate to achieve its aims but emphasized the importance of varying teaching methods and evaluation.

In-vitro expression of adhesion molecules and bone specific markers are depending on the cell culture material.

Bone formation is an active process whereby osteoblasts are found on the surface of the newly formed bone. Adhesion to extracellular matrix is essential for the development of bone however not all surfaces are suitable for osteoblast adhesion and don't support osteoblastic functions. The objective of this study was to test the suitability of a collagen based microcarrier which would support osteoblastic functions.

Modified Alvarado score for acute appendicitis in overweight patients.

OBJECTIVE: To find out the efficacy of Modified Alvarado (MA) scoring system in diagnosis of acute appendicitis in the overweight patients. METHODS: All the patients with suspected acute appendicitis admitted in the surgical department at King Fahad Hospital, Hofuf, Al-Hassa, during the period from September 2004 to December 2006 were included in the study. Patients with score of 7 or more of modified Alvarado score were included, patients with score of 6 or less were excluded. All patients underwent diagnostic laparoscopy, and the diagnosis was confirmed by histopathological examination. RESULTS: There was total of 228 patients. Twenty -four percent were overweight and 12% patients were obese. Sixty percent of the patients had confirmed diagnosis of acute appendicitis. CONCLUSION: Modified Alvarado scoring system is an easy method for diagnosis for acute appendicitis. It can be used as complementary aid for supporting the diagnosis of acute appendicitis in overweight and obese patients.

Assessing the burden of human rabies in India: results of a national multi-center epidemiological survey.

OBJECTIVE: Human rabies has been endemic in India since time immemorial, and the true incidence of the disease and nationwide epidemiological factors have never been studied. The main objectives of the present study were to estimate the annual incidence of human rabies in India based on a community survey and to describe its salient epidemiological features. METHODS: The Association for Prevention and Control of Rabies in India (APCRI) conducted a national multi-center survey with the help of 21 medical schools during the period February-August 2003. This community-based survey covered a representative population of 10.8 million in mainland India. Hospital-based data were also obtained from the 22 infectious diseases hospitals. A separate survey of the islands of Andaman, Nicobar, and Lakshadweep, reported to be free from rabies, was also undertaken. RESULTS: The annual incidence of human rabies was estimated to be 17,137 (95% CI 14,109-20,165). Based on expert group advice, an additional 20% was added to this to include paralytic/atypical forms of rabies, providing an estimate of 20,565 or about 2 per 100000 population. The majority of the victims were male, adult, from rural areas, and unvaccinated. The main animals responsible for bites were dogs (96.2%), most of which were stray. The most common bite sites were the extremities. The disease incubation period ranged from two weeks to six months. Hydrophobia was the predominant clinical feature. Many of the victims had resorted to indigenous forms of treatment following animal bite, and only about half of them had sought hospital attention. Approximately 10% of these patients had taken a partial course of either Semple or a cell culture vaccine. The islands of Andaman, Nicobar, and Lakshadweep were found to be free of rabies. CONCLUSION: Human rabies continues to be endemic in India except for the islands of Andaman, Nicobar, and Lakshadweep. Dogs continue to be the principal reservoir. The disease is taking its toll on adult men and children, the majority from rural areas, due to lack of awareness about proper post-exposure immunization. The keys to success in the further reduction of rabies in India lies in improved coverage with modern rabies vaccines, canine rabies control, and intensifying public education about the disease.

Role of O6-alkylguanine-DNA alkyltransferase in the resistance of mouse spermatogenic cells to O6-alkylating agents.

The O(6)-alkylguanine-DNA alkyltransferase inactivator O(6)-benzylguanine was administered to BALB/c mice either alone or before exposure to 1,3-bis(2-chloroethyl)-1-nitrosourea to study the role of the DNA repair protein O(6)-alkylguanine-DNA alkyltransferase in the protection of the testis against anti-cancer O(6)-alkylating agents. Exposure of the mice to 1, 3-bis(2-chloroethyl)-1-nitrosourea or O(6)-benzylguanine alone did not produce any marked testicular toxicity at the times studied. Testicular O(6)-alkylguanine-DNA alkyltransferase concentrations were assayed between 0 and 240 min after O(6)-benzylguanine treatment and were shown to be > 95% depleted 15 min after treatment with O(6)-benzylguanine and remained at > 95% at all the times assayed. Histological examination, the reduction in testicular mass and the induction of spermatogenic cell apoptosis showed that this depletion significantly potentiated 1, 3-bis(2-chloroethyl)-1-nitrosourea-induced testicular damage after treatment. Major histological damage was apparent 42 days after treatment, demonstrating that the stem spermatogonia were significantly affected by the combination. These results demonstrate that O(6)-alkylguanine-DNA alkyltransferase plays a significant role in protecting the spermatogenic cells from damage caused by DNA alkylation and indicate that the observed toxicity may result from damage to stem spermatogonia.

N-nitrosoephedrine and N-nitrosopseudoephedrine: their dissolution, absorption, blood clearance and elimination studies.

Dissolution and absorption rates (in vitro); clearance from blood and elimination rates of N-nitrosoephedrine (NEP) and N-nitrosopseudophedrine (NPEP) in mice were determined. The two isomers obeyed first-order kinetics and from the slope of the regression line, the rate constant for each study was obtained. These constants were 0.023, 0.038 min-1 (dissolution); 0.192, 0.225 h-1 (stomach absorption); 2.898, 1.980 h-1 (intestinal absorption); 0.33, 0.55 h-1 (blood clearance) and 0.373, 0.393 h-1 (elimination from whole animal) of NEP and NPEP, respectively, and were tested by Student's t-test. Significant differences in the dissolution, absorption and blood clearance rates of NPEP from those of NEP have been observed (P less than 0.05-0.01). These differences are expected to exert their influence on the metabolic rates and the carcinogenic and/or spectral properties of NEP and NPEP, in a related pattern.

Production of nitrosamines from ephedrine, pseudoephedrine and extracts of Ephedra foliata under physiological conditions.

N-Nitrosoephedrine (NEP) and N-nitrosopseudoephedrine (NPEP) were synthesised at 5 degrees C using different concentrations of various acids. The reaction with acetic acid gave the highest yield (85%) of N-nitrosamine. Ephedrine and pseudoephedrine were reacted with nitrite under physiological conditions (37 degrees C, pH 1-3) to form NEP and NPEP. The yield of NEP, which is a known carcinogen, and NPEP were the highest (18.5%) at pH 2. Aqueous and alcoholic extracts of Ephedra foliata (100 g dry wt), nitrosated under physiological conditions, produced 0.77 mg and 8.3 mg, respectively, as total nitrosamines. This indicated the potential of the nitrosamine formation from the plant extracts specified.