Search results for: chronic pulmonary disease

Authors: Memoona Ramzan, Bushra Tabassum, Anwar Khan, Muhammad Tariq, Mudassar Fareed Awan, Idrees Ahmad Nasir, Zahida Qamar, Naila Shahid, Tayyab Husnain

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Biological control is a novel approach being used in crop protection nowadays. Bacteria like Bacillus and Pseudomonas are reported for this purpose and few of their products are commercially available too. Rhizosphere and phyllosphere of healthy cotton plants were used as a source to isolate bacteria capable of exhibiting properties worthy for selection as biocontrol agent. For this purpose all isolated strains were screened for the activities like phosphate solubilization, Indole acetic acid (IAA) production and biocontrol against fungi. Two strains S1HL3 and S1HL4 showed phosphate solubilization and IAA production simultaneously while two other JS2HR4 and JS3HR2 were good inhibitors of fungal pathogens. Through biochemical and molecular characterization these bacteria were identified as P. aeruginosa, Burkholderia and Bacillus respectively. In green house trials of these isolates against Cotton leaf curl virus (CLCuV), seven treatments including individual bacterial isolate and consortia were included. Treated plants were healthy as compared to control plants in which upto 74% CLCuV symptomatic plants exist. Maximum inhibition of CLCuV was observed in T7 treated plants where viral load was only 0.4% as compared to control where viral load was upto 74%. This treatment consortium included Bacillus and Pseudomonas isolates; S1HL3, S1HL4, JS2HR4 and JS3HR2. Principal Component Biplot depicted highly significant correlation between percentage viral load and the disease incidence.

Keywords: cotton leaf curl virus, biological control, bacillus, pseudomonas

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Authors: Deepak Mohan, Sushma Sharma

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Diclofenac sodium, a member of the acetic acid family of non-steroidal anti-inflammatory drugs, is used to retard inflammation, arthritis pain and ankylosing spondylitis. The drug is known to cause severe injury in different tissues due to formation of reactive oxygen species. The present study is focused on the effect of different doses of diclofenac (4 mg/kg/body weight and 14 mg/kg/body weight on histoarchitecture of the liver from 7-28 days of the investigation. Diclofenac administration resulted in distorted hepatic degeneration and formation of wide areas in the form of sinusoidal gaps. Hepatic fibrosis noticed in different stages of investigation could be attributed to chronic inflammation and reactive oxygen species which results in deposition of extracellular matrix proteins. The abrupt degenerative changes observed during later stages of the experiment showed maximum damage to the liver, and there was enlargement of sinusoidal gaps accompanied by maximum necrosis in the tissues.

Keywords: arthritis, diclofenac, histoarchitecture, sinusoidal

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Authors: O. I. Adeniran, M. A. Mogale

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Advanced glycation end-products (AGEs) have been implicated in the development and progression of vascular complications of diabetes mellitus and other age-related disease such as Alzheimer’s disease, heart diseases, stroke and limb amputation. The aim of the study was to determine the anti-glycation activity and AGE-cross-linking breaking ability of Sclerocarya birrea stem-bark extracts (SBSBETs). Hexane, ethyl acetate, methanol and water extracts of Sclerocarya birrea stem-bark and standard inhibitor, aminoguanidine (AG) were incubated with bovine serum albumin (BSA)-fructose mixture for 20 and 40 days. The amounts of total immunogenic AGEs (TIAGEs), fluorescent AGEs (FAGEs) and carboxymethyl lysine (CML) formed were determined and the percentage anti-glycation activity of each plant extract calculated. The ability of SBSBETs to break fructose-derived BSA-AGE-collagen cross-links was also investigated. All SBSBETs under investigation demonstrated less anti-glycation activity against TIAGE, FAGEs and CML than AG after 20 days incubation. After 40 days incubation, ethyl acetate, methanol and water SBSBETs demonstrated lower anti-glycation activity against TIAGEs than AG but exerted higher anti-glycation activity than AG against FAGEs. All SBSBETs except water demonstrated lower anti-glycation activity than AG against CML. With regard to the ability of SBSBETs to breakdown fructose-derived AGEs cross-links, the polar SBSBETs demonstrated higher ability to break AGE-cross-links than the non-polar ones. The results of this study may lead to the isolation of bio-active phyto-chemicals from SBSBETs that may be used for the prevention of vascular complication of diabetes.

Keywords: advanced glycation end-products, anti-glycation, cross-link breaking, Sclerocarrya birrea

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Authors: Federico Cevoli

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Purinergic P2X7 receptors (P2X7R) are ligand-gated non-selective cation channels involved in several physiological and pathological processes. They are particularly promising pharmacological targets as they are present in an increasing number of different cells types. P2X7R activation is triggered following elevated concentrations of extracellular ATP, similarly to those observed in tissues injury, chronic inflammation and T-cell activation, as well as in the scrambling of phospholipids leading to membrane blebbing and apoptosis. Another hallmark of P2X7 is cell permeabilization, commonly known as “macropore” formation allowing the passage of nanometer-sized molecules up to 900Da. Recently, full-length P2X7 Cryo-EM structures revealed unique functional sites, including two cytoplasmic domains - the cytoplasmic "anchor" and "ballast". To date, the molecular units/complex by which P2X7R exerts its pathophysiological functions are unknown. Using custom-made cell-penetrating HIV-1 TAT peptides, we show for the first-time potential implications of P2X7 cytoplasmic anchor in the regulation of caspase3/7 activation as well as TNFα regulation.

Keywords: P2X7R, immunology, TAT-peptide, cell death

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Authors: Younus Mohammad, Anita B. Fallah, Ben J. Boyd, Shakila B. Rizwan

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N-acylethanolamines (NAEs) are endogenous lipids, which have neuromodulatory properties. NAEs have shown neuroprotective properties in various neurodegenerative diseases including Alzheimer's disease, Parkinson's disease and ischemic stroke. However, NAEs are eliminated rapidly in vivo by enzymatic hydrolysis. We propose to encapsulate NAEs in liquid crystalline nanoparticles (cubosomes) to increase their biological half-life and explore their therapeutic potential. Recently, we have reported the co-formulation and nanostructural characterization of cubosomes containing the NAE, oleoylethanolamide and a synthetic cubosome forming lipid phytantriol. Here, we report on the formulation of cubosomes with the NAE, linoleoylethanolamide (LEA) as the core cubosome forming lipid. LEA-cubosomes were formulated in the presence of three different steric stabilisers: two brain targeting ligands, Tween 80 and Pluronic P188 and a control, Pluronic F127. Size, morphology and internal structure of formulations were characterized by dynamic light scattering (DLS), cryogenic transmission electron microscopy (Cryo–TEM) and small angle X–ray scattering (SAXS), respectively. Chemical stability of LEA in formulations was investigated using high-performance liquid chromatography (HPLC). Cytotoxicity of formulations towards human cerebral microvascular endothelial cell line (hCMEC/D3) was also investigated using an MTT (3-[4, 5- dimethylthiazol-2-yl]-2, 5-diphenyl tetrazolium bromide) assay. All cubosome formulations had mean particle size of less than 250 nm and were uniformly distributed with polydispersity indices less than 0.2. Cubosomes produced had a bicontinuous cubic internal structure with an Im3m space group but different lattice parameters, indicating the different modes of interaction between the stabilisers and LEA. LEA in formulations was found to be chemically stable. At concentrations of up to 20 µg/mL LEA in the presence of all the stabilisers, greater than 80% cell viability was observed.

Keywords: blood-brain barrier, cubosomes, linoleoyl ethanolamide, N-acylethanolamines (NAEs)

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Authors: Min-Tao Hsu

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This study aims to explore the lived experiences of women with breast cancer, including their life world of illness and their adaptation to breast cancer. Breast cancer is not only a potentially lethal disease, but also a disease that may lead to many irreversible changes for female patients. Especially, in a culture where the wholeness is pursuit as an essential value, the sickness and/or broken body bring great challenge of life. Based on holism and symbolic interactionism, this study used interpretive ethnography including in-depth interviews and participant observations to collect the narrative of women with breast cancer concerning their illness experience. In addition, this study used Agar’s hermeneutic cycle to analyze data. The average age of 35 participants was 54.2. A total of 15 patients were within 2 years of onset, 5 patients were within 2-5 years of the treatment observation period, and 15 patients suffered from breast cancer for more than 5 years. The average age of onset was 50.4. Result: The main storyline of the life world of illness is ‘breast cancer is a turning point of life.’ Loss of breast was in terms of ‘no more a woman’ in Taiwanese culture. Two young women, one in her newly wedded and another right before marry, were divorced and cancelled wedding right after being diagnosed. All of them addressed that they have a ‘broken body.’ Single women accounted that they won’t marry for not being humiliated and most of married women said they never show female body in front of her husband or partner even in intimacy encounter. Three common themes were discovered: 1) new self and new identity; 2) new social relationships and new me; 3) new body and new life. The intertwining bodies, illness, selves, suffering, and medical treatments of female patients were observed. More, the recovery, of cause, was happened when new self, relationship, and new body were generated. Their identity to be a woman and a wife is shattered and their life is urged into another facet. For helping them to recovery from such situation, building a new identity and new social fabric on the new body need to be included in nursing care plan.

Keywords: breast cancer, illness narrative, world of illness, self-healing, interpretive ethnography

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Authors: T. Arkle, D. Pournaras, S. Lam, B. Kumar

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Introduction: Fundoplication is widely recognised as the best surgical option for gastro-oesophageal reflux disease (GORD) in the general population. However, there is controversy surrounding the use of conventional fundoplication in obese patients. Whilst the intra-operative failure of fundoplication, including wrap disruption, is reportedly higher in obese individuals, the more significant issue surrounds symptom recurrence post-surgery. Could a bariatric procedure be considered in obese patients for weight management, to treat the GORD, and to also reduce the risk of recurrence? Roux-en-Y gastric bypass, a widely performed bariatric procedure, has been shown to be highly successful both in controlling GORD symptoms and in weight management in obese patients. Furthermore, NICE has published clear guidelines on eligibility for bariatric surgery, with the main criteria being type 3 obesity or type 2 obesity with the presence of significant co-morbidities that would improve with weight loss. This study aims to identify the proportion of patients who undergo conventional fundoplication for GORD and/or hiatus hernia, which would have been eligible for bariatric surgery referral according to NICE guidelines. Methods: All patients who underwent fundoplication procedures for GORD and/or hiatus hernia repair at a single NHS foundation trust over a 10-year period will be identified using the Trust’s health records database. Pre-operative patient records will be used to find BMI and the presence of significant co-morbidities at the time of consideration for surgery. This information will be compared to NICE guidelines to determine potential eligibility for the bariatric surgical referral at the time of initial surgical intervention. Results: A total of 321 patients underwent fundoplication procedures between January 2011 and December 2020; 133 (41.4%) had available data for BMI or to allow BMI to be estimated. Of those 133, 40 patients (30%) had a BMI greater than 30kg/m², and 7 (5.3%) had BMI >35kg/m². One patient (0.75%) had a BMI >40 and would therefore be automatically eligible according to NICE guidelines. 4 further patients had significant co-morbidities, such as hypertension and osteoarthritis, which likely be improved by weight management surgery and therefore also indicated eligibility for referral. Overall, 3.75% (5/133) of patients undergoing conventional fundoplication procedures would have been eligible for bariatric surgical referral, these patients were all female, and the average age was 60.4 years. Conclusions: Based on this Trust’s experience, around 4% of obese patients undergoing fundoplication would have been eligible for bariatric surgical intervention. Based on current evidence, in class 2/3 obese patients, there is likely to have been a notable proportion with recurrent disease, potentially requiring further intervention. These patient’s may have benefitted more through undergoing bariatric surgery, for example a Roux-en-Y gastric bypass, addressing both their obesity and GORD. Use of patient written notes to obtain BMI data for the 188 patients with missing BMI data and further analysis to determine outcomes following fundoplication in all patients, assessing for incidence of recurrent disease, will be undertaken to strengthen conclusions.

Keywords: bariatric surgery, GORD, Nissen fundoplication, nice guidelines

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Authors: Yuli Hou, Jianping Sun, Mengdan Gao, Hui Liu, Ling Qin, Ang Li, Dongfu Li, Yonghong Zhang, Yan Zhao

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Background and Aims: Interferon-induced transmembrane protein 3 (IFITM3) is a component of ISG (Interferon-Stimulated Gene) family. IFITM3 has been recognized as a key signal molecule regulating cell growth in some tumors. However, the function of IFITM3 rs12252-CC genotype in the hepatocellular carcinoma (HCC) remains unknown to author’s best knowledge. A cohort study was employed to clarify the relationship between IFITM3 rs12252-CC genotype and HCC progression, and cellular experiments were used to investigate the correlation of function of IFITM3 and the progress of HCC. Methods: 336 candidates were enrolled in study, including 156 with HBV related HCC and 180 with chronic Hepatitis B infections or liver cirrhosis. Polymerase chain reaction (PCR) was employed to determine the gene polymorphism of IFITM3. The functions of IFITM3 were detected in PLC/PRF/5 cell with different treated:LV-IFITM3 transfected with lentivirus to knockdown the expression of IFITM3 and LV-NC transfected with empty lentivirus as negative control. The IFITM3 expression, proliferation and migration were detected by Quantitative reverse transcription polymerase chain reaction (qRT-PCR), QuantiGene Plex 2.0 assay, western blotting, immunohistochemistry, Cell Counting Kit(CCK)-8 and wound healing respectively. Six samples (three infected with empty lentiviral as control; three infected with LV-IFITM3 vector lentiviral as experimental group ) of PLC/PRF/5 were sequenced at BGI (Beijing Genomics Institute, Shenzhen,China) using RNA-seq technology to identify the IFITM3-related signaling pathways and chose PI3K/AKT pathway as related signaling to verify. Results: The patients with HCC had a significantly higher proportion of IFITM3 rs12252-CC compared with the patients with chronic HBV infection or liver cirrhosis. The distribution of CC genotype in HCC patients with low differentiation was significantly higher than that in those with high differentiation. Patients with CC genotype found with bigger tumor size, higher percentage of vascular thrombosis, higher distribution of low differentiation and higher 5-year relapse rate than those with CT/TT genotypes. The expression of IFITM3 was higher in HCC tissues than adjacent normal tissues, and the level of IFITM3 was higher in HCC tissues with low differentiation and metastatic than high/medium differentiation and without metastatic. Higher RNA level of IFITM3 was found in CC genotype than TT genotype. In PLC/PRF/5 cell with knockdown, the ability of cell proliferation and migration was inhibited. Analysis RNA sequencing and verification of RT-PCR found out the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin(PI3K/AKT/mTOR) pathway was associated with knockdown IFITM3.With the inhibition of IFITM3, the expression of PI3K/AKT/mTOR signaling pathway was blocked and the expression of vimentin was decreased. Conclusions: IFITM3 rs12252-CC with the higher expression plays a vital role in the progress of HCC by regulating HCC cell proliferation and migration. These effects are associated with PI3K/AKT/mTOR signaling pathway.

Keywords: IFITM3, interferon-induced transmembrane protein 3, HCC, hepatocellular carcinoma, PI3K/ AKT/mTOR, phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin

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Authors: Rieski Prihastuti, Meliana Depo, Trisno A. Wibowo, Misinem

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On October 19, 2017, Yogyakarta Islamic Hospital reported 38 garment employees with nausea, vomiting, headache, abdominal pain, and diarrhea after they had lunch on October 18, 2017, to Sleman District Health Office. Objectives of this study were to ensure the outbreak and identify source and route of transmission. Case-control study was conducted to analyze food items that caused the outbreak. A case was defined as a person who got symptoms such as abdominal pain, diarrhea, nausea with/without vomiting, fever, and headache after they had lunch on October 18, 2017. Samples included leftover lunch box, vomit, tap water and drinking water had been sent to the laboratory. Data were analyzed descriptively as frequency table and analyzed by using chi-square in bivariate analysis. All of 196 garment employee was included in this study. The common symptoms of this outbreak were abdominal pain (84.4%), diarrhea (72.8%), nausea (61.6%), headache (52.8%), vomiting (12.8%), and fever (6.4%) with median incubation period 13 hours (range 1-34 hours). Highest attack rate and odds ratio was found in grilled chicken (Attack Rate 58,49%) with Odds Ratio 11,023 (Confidence Interval 95% 1.383 - 87.859; p value 0,005). Almost all samples showed mold, except drinking water. Based on its sign and symptoms, also incubation period, diarrheal Bacillus cereus and Clostridium perfringens were suspected to be the causative agent of the outbreak. Limitation of this study was improper sample handling and no sample of food handler and stools in the food caterer. Outbreak investigation training needed to be given to the hospital worker, and monitoring should be done to the food caterer to prevent another outbreak.

Keywords: disease outbreak, foodborne disease, food poisoning, outbreak

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Authors: Khayra Zerrouki, Noureddine Djebli, Esra Eroglu, Afife Mat, Ozhan Gul

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Neurodegenerative diseases of the human brain comprise a variety of disorders that affect an increasing percentage of the population. Alzheimer’s disease (AD) is a complex, multifactorial, heterogeneous mental illness, which is characterized by an age-dependent loss of memory and an impairment of multiple cognitive functions, but this 10 last years it concerns the population most and most young. Hypericum perforatum has traditionally been used as an external anti-inflammatory and healing remedy for the treatment of swellings, wounds and burns, diseases of the alimentary tract and psychological disorders. It is currently of great interest due to new and important therapeutic applications. In this study, the chemical composition of methanolic extract of Hypericum perforatum (HPM) was analysed by using high performance liquid chromatography – diode array detector (HPLC-DAD). The in vitro antioxidant activity of HPM was evaluated by using several antioxidant tests. HSM exhibits inhibitory capacity against posphatidylcholine liposome peroxidation, induced with iron and ascorbic acid, scavenge DPPH and superoxide radicals and act as reductants. The cytotoxic activity of HSM was also determined by using MTT cell viability assay on HeLa and NRK-52E cell lines. The in vivo activity studies in Swiss mice were determined by using behavioral, memory tests and histological study. According to tests results HPM that may be relevant to the treatment of cognitive disorders. The results of chemical analysis showed a hight level of hyperforin and quercitin that had an important antioxidant activity proved in vitro with the DPPH, anti LPO and SOD; this antioxidant activity was confirmed in vivo after the non-toxic results by means of improvement in behavioral and memory than the reducing shrunken in pyramidal cells of mice brains.

Keywords: AlCl3, alzheimer, mice, neuroprotective, neurotoxicity, phytotherapy

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Authors: Balakrishna Shetty

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Introduction: Stem Cell Imaging is a challenging field since the advent of Stem Cell treatment in humans. Series of research on tagging and tracking the stem cells has not been very effective. The present study is an effort by the authors to track the stem cells injected into calf muscles by Magnetic Resonance Diffusion Weighted Imaging. Materials and methods: Stem Cell injection deep into the calf muscles of patients with peripheral vascular disease is one of the recent treatment modalities followed in our institution. 5 patients who underwent deep intramuscular injection of stem cells as treatment were included for this study. Pre and two hours Post injection MRI of bilateral calf regions was done using 1.5 T Philips Achieva, 16 channel system using 16 channel torso coils. Axial STIR, Axial Diffusion weighted images with b=0 and b=1000 values with back ground suppression (DWIBS sequence of Philips MR Imaging Systems) were obtained at 5 mm interval covering the entire calf. The invert images were obtained for better visualization. 120ml of autologous bone marrow derived stem cells were processed and enriched under c-GMP conditions and reduced to 40ml solution containing mixture of above stem cells. Approximately 40 to 50 injections, each containing 0.75ml of processed stem cells, was injected with marked grids over the calf region. Around 40 injections, each of 1ml normal saline, is injected into contralateral leg as control. Results: Significant Diffusion hyper intensity is noted at the site of injected stem cells. No hyper intensity noted before the injection and also in the control side where saline was injected conclusion: This is one of the earliest studies in literature showing diffusion hyper intensity in intramuscularly injected stem cells. The advantages and deficiencies in this study will be discussed during the presentation.

Keywords: stem cells, imaging, DWI, peripheral vascular disease

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Authors: Mukul Sharma, Madhusmita Das, Sundeep Chaitanya Vedithi

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Leprosy is a chronic human disease caused by Mycobacterium leprae, that cannot be cultured in vitro. Though treatable with multidrug therapy (MDT), recently, bacteria reported resistance to multiple antibiotics. Targeting DNA replication and repair pathways can serve as the foundation of developing new anti-leprosy drugs. Due to the absence of an axenic culture medium for the propagation of M. leprae, studying cellular processes, especially those belonging to DNA repair pathways, is challenging. Genomic understanding of M. Leprae harbors several protein-coding genes with no previously assigned function known as 'hypothetical proteins'. Here, we report identification and expression of known and hypothetical DNA repair genes from a human skin biopsy and mouse footpads that are involved in base excision repair, direct reversal repair, and SOS response. Initially, a bioinformatics approach was employed based on sequence similarity, identification of known protein domains to screen the hypothetical proteins in the genome of M. leprae, that are potentially related to DNA repair mechanisms. Before testing on clinical samples, pure stocks of bacterial reference DNA of M. leprae (NHDP63 strain) was used to construct standard graphs to validate and identify lower detection limit in the qPCR experiments. Primers were designed to amplify the respective transcripts, and PCR products of the predicted size were obtained. Later, excisional skin biopsies of newly diagnosed untreated, treated, and drug resistance leprosy cases from SIHR & LC hospital, Vellore, India were taken for the extraction of RNA. To determine the presence of the predicted transcripts, cDNA was generated from M. leprae mRNA isolated from clinically confirmed leprosy skin biopsy specimen across all the study groups. Melting curve analysis was performed to determine the integrity of the amplification and to rule out primer‑dimer formation. The Ct values obtained from qPCR were fitted to standard curve to determine transcript copy number. Same procedure was applied for M. leprae extracted after processing a footpad of nude mice of drug sensitive and drug resistant strains. 16S rRNA was used as positive control. Of all the 16 genes involved in BER, DR, and SOS, differential expression pattern of the genes was observed in terms of Ct values when compared to human samples; this was because of the different host and its immune response. However, no drastic variation in gene expression levels was observed in human samples except the nth gene. The higher expression of nth gene could be because of the mutations that may be associated with sequence diversity and drug resistance which suggests an important role in the repair mechanism and remains to be explored. In both human and mouse samples, SOS system – lexA and RecA, and BER genes AlkB and Ogt were expressing efficiently to deal with possible DNA damage. Together, the results of the present study suggest that DNA repair genes are constitutively expressed and may provide a reference for molecular diagnosis, therapeutic target selection, determination of treatment and prognostic judgment in M. leprae pathogenesis.

Keywords: DNA repair, human biopsy, hypothetical proteins, mouse footpads, Mycobacterium leprae, qPCR

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Authors: Nazira B. Bekenova, Lydia A. Mukovozova, Andrej M. Grjibovski, Alma Z. Tokayeva, Yerbol M. Smail, Nurlan E. Aukenov

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Erysipelas is an infectious disease with socio-economic significance and prone to prolonged recurrent course (30%). Contribution of genetic factors, in particular the gene polymorphism of cytokines, can be essential in disease etiology and pathogenesis. Interleukin – 17 A are produced by T helpers of 17 type and plays a key role in development of local inflammation process. Local inflammatory process is a dominant in the clinic of erysipelas. Established that the skin and mucosas are primary areas of migration (homing) Th17-cell and their cytokines are stimulate the barrier function of the epithelium. We studied associations between gene polymorphism of IL-17A (C737T) rs 8193036 and IL-17A level in patients with erysipelas Kazakh population. Altogether, 90 cases with erysipelas and 90 healthy controls from an ethnic Kazakh population comprised the sample. Cases were identified at Clinical Infectious Diseases Hospital of Semey (Kazakhstan). The IL-17A (rs8193036) polymorphism was analyzed by a real time polymerase chain reaction. Plasma levels of IL-17 A were assessed by immuneenzyme analysis method using ‘Vector-Best’ test-system (Russia). Differences in levels of IL-17 A between CC, TT, CT groups were studied using Kruskal — Wallis test. Pairwise comparisons were performed using Mann-Whitney tests with Bonferroni correction (New significance level was set to 0.025). We found, that in patients with erysipelas with CC genotype the level of IL-17 A was higher (p= 0, 010) compared to the carriers of CT genotype. When compared the level of IL – 17 A between the patients with TT genotype and patients with CC genotype, also between the patients with CT genotype and patients with TT genotype statistically significant differences are not revealed (p = 0.374 and p = 0.043, respectively). Comparisons of IL-17 A plasma levels between the CC and CT genotypes, between the CC and TT genotypes, and between the TT and CT in healthy patients did not reveal significant differences (p = 0, 291). Therefore, we are determined the associations of gene polymorphism of IL-17 A (C737T) with its level in patients erysipelas carriers CC genotype.

Keywords: erysipelas, interleukin – 17 A, Kazakh, polymorphism

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Authors: Paul Anyaogu, E. U. M. Igbo

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This study examines the public view on child street hawking in Aba Urban, Abia State, Nigeria, its causes and effect on the child participant and society at large. The study tends to investigate the influence of socioeconomic status on child street hawking. The current situation reflects a chronic urban poverty, which disposed of parents/guardians to send their children and wards of school age to income yielding activities. A social survey research design was employed to select the respondents. A total of 1,108 questionnaires were administered to the respondents of 18 years and above and 1,038 were retrieved. Also, 24 in-depth interviews were conducted in the study area. The findings revealed that child street hawking is on the increase and a serious threat to social cohesion and national security. The study also revealed that poverty is a major cause of child street hawking. The study recommends that government should create job opportunities for urban dwellers, as well as provide social amenities and also put up poverty alleviation/eradication programmes for the people.

Keywords: Aba Urban, child street hawking, dangers, disposition, poverty

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Authors: Nabil Omar, Farah Jibril, Oraib Amjad

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Purpose: Trabecatine is a is a potent marine-derived antineoplastic drug which binds to the minor groove of the DNA, bending DNA towards the major groove resulting in a changed conformation that interferes with several DNA transcription factors, repair pathways and cell proliferation. Trabectedin was approved by the European Medicines Agency (EMA; London, UK) for the treatment of adult patients with advanced stage soft tissue sarcomas in whom treatment with anthracyclines and ifosfamide has failed, or for those who are not candidates for these therapies. The recommended dosing regimen is 1.5 mg/m2 IV over 24 hours every 3 weeks. The purpose of this study was to comprehensively review available data on the safety and efficacy of trabectedin used as indicated for patients at a Tertiary Cancer Center at Qatar. Methods: A medication administration report generated in the electronic health record identified all patients who received trabectedin between November 1, 2015 and November 1, 2017. This retrospective chart review evaluated the indication of trabectedin use, compliance to administration protocol and the recommended monitoring parameters, number of patients improved on the drug and continued treatment, number of patients discontinued treatment due to side-effects and the reported side effects. Progress and discharged notes were utilized to report experienced side effects during trabectedin therapy. A total of 3 patients were reviewed. Results: Total of 2 out of 3 patients who received trabectedin were receiving it for non-FDA and non-EMA, approved indications; metastatic rhabdomyosarcoma and ovarian cancer stage IV with poor prognosis. And only one patient received it as indicated for leiomyosarcoma of left ureter with metastases to liver, lungs and bone. None of the patients has continued the therapy due to development of serious side effects. One patient had stopped the medication after one cycle due to disease progression and transient hepatic toxicity, the other one had disease progression and developed 12 % reduction in LVEF after 12 cycles of trabectedin, and the third patient deceased, had disease progression on trabectedin after the 10th cycle that was received through peripheral line which resulted in developing extravasation and left arm cellulitis requiring debridement. Regarding monitoring parameters, at baseline the three patients had ECHO, and Creatine Phosphokinase (CPK) but it was not monitored during treatment as recommended. Conclusion: Utilizing this medication as indicated with performing the appropriate monitoring parameters as recommended can benefit patients who are receiving it. It is important to reinforce the intravenous administration via central intravenous line, the re-assessment of left ventricular ejection fraction (LVEF) by echocardiogram or multigated acquisition (MUGA) scan at 2- to 3-month intervals thereafter until therapy is discontinued, and CPK and LFTs levels prior to each administration of trabectedin.

Keywords: trabectedin, drug-use evaluation, safety, effectiveness, adverse drug reaction, monitoring

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Authors: Wafa Al Jabri

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Sickle cell disease (SCD) is a genetic blood disorder that is characterized by a severe painful crisis. SCD among children requires long term dependencies and high caregiving demands that increase the overall family burdens. It is, therefore, essential to examine, support, and promote the well-being of families of children with SCD. Although there has been considerable progress in the international research on family quality of life (FQOL) in recent years; however, research in this field is relatively recent and diverse. Oman is a country in which family quality of life has definitely been under-researched. Therefore, the purpose of the study is to describe the FQOL in families of children with SCD in Oman. The study will also examine the relationships between child, mother, and family-related factors that may influence the overall FQOL. Theoretical Framework: The study is guided by the unified theory of family quality of life to help in understanding the concept of FQOL and the factors that shape it. Method:A convenience sample of 98 mothers of children with SCD will be recruited from the pediatric hematology clinic at Sultan Qaboos University Hospital in Oman to participate in this descriptive, cross sectional, correlational study. Data will be obtained using a self-administered questionnaire that includes child and mother socio-demographic data, questions about the number of visits and admissions to health care facilities for vaso- occlusive crises (VOCs), the Perceived Stress Scale-10, and the Beachcenter-FQOL scale. Anticipated Results: It is expected to find an association among frequency of VOCs, mother’s perceived stress level, and FQOL in families of children with SCD in Oman. Family type, socio-economic status, and number of SCD children in the family are also expected to influence the overall FQOL. Conclusion: The findings of the study might be pivotal in designing and implementing tailored family-based interventions to improve families’ wellbeing.

Keywords: family quality of life, sickle cell disaes, children, family well-being

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Authors: Tamar Lin, Nufar Buchshtab, Yifat Elharar, Julian Nicenboim, Rotem Edgar, Iddo Weiner, Lior Zelcbuch, Ariel Cohen, Sharon Kredo-Russo, Inbar Gahali-Sass, Naomi Zak, Sailaja Puttagunta, Merav Bassan

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Background: Atopic dermatitis (AD) is a chronic, relapsing inflammatory skin disorder that is characterized by dry skin and flares of eczematous lesions and intense pruritus. Multiple lines of evidence suggest that AD is associated with increased colonization by Staphylococcus aureus, which contributes to disease pathogenesis through the release of virulence factors that affect both keratinocytes and immune cells, leading to disruption of the skin barrier and immune cell dysfunction. The aim of the current study is to develop a bacteriophage-based product that specifically targets S. aureus. Methods: For the discovery of phage, environmental samples were screened on 118 S. aureus strains isolated from skin samples, followed by multiple enrichment steps. Natural phages were isolated, subjected to Next-generation Sequencing (NGS), and analyzed using proprietary bioinformatics tools for undesirable genes (toxins, antibiotic resistance genes, lysogeny potential), taxonomic classification, and purity. Phage host range was determined by an efficiency of plating (EOP) value above 0.1 and the ability of the cocktail to completely lyse liquid bacterial culture under different growth conditions (e.g., temperature, bacterial stage). Results: Sequencing analysis demonstrated that the 118 S. aureus clinical strains were distributed across the phylogenetic tree of all available Refseq S. aureus (~10,750 strains). Screening environmental samples on the S. aureus isolates resulted in the isolation of 50 lytic phages from different genera, including Silviavirus, Kayvirus, Podoviridae, and a novel unidentified phage. NGS sequencing confirmed the absence of toxic elements in the phages’ genomes. The host range of the individual phages, as measured by the efficiency of plating (EOP), ranged between 41% (48/118) to 79% (93/118). Host range studies in liquid culture revealed that a subset of the phages can infect a broad range of S. aureus strains in different metabolic states, including stationary state. Combining the single-phage EOP results of selected phages resulted in a broad host range cocktail which infected 92% (109/118) of the strains. When tested in vitro in a liquid infection assay, clearance was achieved in 87% (103/118) of the strains, with no evidence of phage resistance throughout the study (24 hours). A S. aureus host was identified that can be used for the production of all the phages in the cocktail at high titers suitable for large-scale manufacturing. This host was validated for the absence of contaminating prophages using advanced NGS methods combined with multiple production cycles. The phages are produced under optimized scale-up conditions and are being used for the development of a topical formulation (BX005) that may be administered to subjects with atopic dermatitis. Conclusions: A cocktail of natural phages targeting S. aureus was effective in reducing bacterial burden across multiple assays. Phage products may offer safe and effective steroid-sparing options for atopic dermatitis.

Keywords: atopic dermatitis, bacteriophage cocktail, host range, Staphylococcus aureus

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Authors: Mujahid Ali, Wasif Mohammed Ali, Meraj Ahmad

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Background: Perforation peritonitis is the most common surgical emergency encountered by surgeons all over the world as well as in India. The etiology of perforation peritonitis in India continues to be different from its western counterparts. The aim of this study is to evaluate the spectrum of cases of perforation peritonitis at our hospital. Methods: A prospective study conducted includes three hundred thirtysix patients of perforation peritonitis at J. N. Medical College from October 2015 to July 2017. The patients were admitted, resuscitated and underwent emergency laparotomy. Data were collected in terms of demographic profile, clinical presentations, site of perforations, causes and surgical outcomes. Results: In this study, the most common cause of perforation peritonitis was peptic ulcer disease (43%), followed by enteric perforation (12.8%), tubercular perforation (12.5%), traumatic perforation (11.9%), appendicular perforation (9.8%), amoebic caecal perforation (3%), malignant perforation (1.5%), etc. The sites of perforations were stomach in majority (38.3%), ileum (31%), appendix (8%), duodenum (5.%), caecum (4.4%) ,colon (3%), jejunum (8.5%) and gall bladder (2%). The overall mortality was 21% in our study. Age >50 years (p= <0.0001, OR= 3.9260, CI= 2.2 to 6.9), organ failure (p= <0.0001, OR= 29.2, CI= 14.8 to 57.6), shock (p=<0.0001, OR=20.20, CI= 10.56 to 38.6), diffuse peritonitis (p<0.0015, OR= 6.8810, CI= 2.09 to 22.57) and faecal exudates (p<0.0001) were found to be significant factors affecting mortality. The most common complication associated was superficial wound infection (40%), followed by burst abdomen seen in 21% cases, intra-abdominal sepsis in 18% cases, electrolyte imbalances in 15% cases, anastomotic leak in 6% cases. Conclusion: In this study, stomach is the most common site of perforation with peptic ulcer disease being the most common etiology. Older age, presence of shock, organ failure and faecal peritonitis were the risk factors affecting the mortality of the patients. Early recognition, adequate resuscitation and referral of patients can influence outcome and reduces mortality as well as morbidity.

Keywords: etiology, mortality, perforation, spectrum

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Authors: Dovilė Bačėninaitė, Karina Džermeikaitė, Justinas Kirvela, Ramūnas Antanaitis

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Bacteria are often present in the mouth of cattle. Some of them can cause abscesses. Starting with severe swelling of the mouth, muscle spasm, or locked jaw, it can lead to inability to open its mouth, move the neck, cause pain while eating. While the calf is unable to eat properly, it becomes more susceptible to infectious diseases, lower weight gain can be observed. Abscesses can be considered as a continuum of oral disease, whereby early stages of the lumpy jaw could proceed from gingivitis to periodontal disease. In the event of tissue damage, bacteria can enter the bloodstream, even cause sepsis. The most common lesions occur when animals eat sharp grass, coarse fodder, sharp, piercing foreign bodies (this is especially common for calves when they are trying to eat inedible objects). A crossbred Holstein calf presented with a history of proliferative outgrowth in the mandibular region. On clinical examination, needle aspiration, mandibular swelling revealed sticky, white curd-like fluid containing. Pus bacteriology revealed gram-negative cocci. They were sensitive to amoxicillin, cephalexin, enrofloxacin, ceftiofur. Blood morphology was in physiological ranges. The calf was treated surgically. The growth was excised, the puss drained and the wound was flushed with potassium permanganate solution (0,01%). A week after clinical surgery examination was performed. The swelling was decreased. Superficial bacterial infections are often associated with poor hygiene, which should be improved before treatment is commenced. Clipping away dirty hair and gently washing affected areas of skin daily with solutions such as povidone-iodine, potassium permanganate is effective. Appropriate antibiotic therapy, based on sensitivity testing, may be used where there is evidence of systemic illness.

Keywords: calf, abscess, lumpy jaw, pus, Streptococcus, Staphylococcus, Actinobacillus, infection

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Authors: Marina Shargorodsky

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Aim: Gestational weight gain (GWG) has been related to altering future weight-gain curves and increased risks of obesity later in life. Obesity may contribute to vascular atherosclerotic changes as well as excess cardiovascular morbidity and mortality observed in these patients. Noninvasive arterial testing, such as ultrasonographic measurement of carotid IMT, is considered a surrogate for systemic atherosclerotic disease burden and is predictive of cardiovascular events in asymptomatic individuals as well as recurrent events in patients with known cardiovascular disease. Currently, there is no consistent evidence regarding the vascular impact of excessive GWG. The present study was designed to investigate the impact of GWG on early atherosclerotic changes during late pregnancy, using intima-media thickness, as well as placental vascular circulation and inflammatory lesions and pregnancy outcomes. Methods: The study group consisted of 59 pregnant women who gave birth and underwent a placental histopathological examination at the Department of Obstetrics and Gynecology, Edith Wolfson Medical Center, Israel, in 2019. According to the IOM guidelines the study group has been divided into two groups: Group 1 included 32 women with pregnancy weight gain within recommended range; Group 2 included 27 women with excessive weight gain during pregnancy. The IMT was measured from non-diseased intimal and medial wall layers of the carotid artery on both sides, visualized by high-resolution 7.5 MHz ultrasound (Apogee CX Color, ATL). Placental histology subdivided placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion according to the criteria of the Society for Pediatric Pathology, subdividing placental findings to lesions consistent with maternal vascular and fetal vascular malperfusion, as well as the inflammatory response of maternal and fetal origin. Results: IMT levels differed between groups and were significantly higher in Group 1 compared to Group 2 (0.7+/-0.1 vs 0.6+/-0/1, p=0.028). Multiple linear regression analysis of IMT included variables based on their associations in univariate analyses with a backward approach. Included in the model were pre-gestational BMI, HDL cholesterol and fasting glucose. The model was significant (p=0.001) and correctly classified 64.7% of study patients. In this model, pre-pregnancy BMI remained a significant independent predictor of subclinical atherosclerosis assessed by IMT (OR 4.314, 95% CI 0.0599-0.674, p=0.044). Among placental lesions related to fetal vascular malperfusion, villous changes consistent with fetal thrombo-occlusive disease (FTOD) were significantly higher in Group 1 than in Group 2, p=0.034). In Conclusion, the present study demonstrated that excessive weight gain during pregnancy is associated with an adverse effect on early stages of subclinical atherosclerosis, placental vascular circulation and neonatal complications. The precise mechanism for these vascular changes, as well as the overall clinical impact of weight control during pregnancy on IMT, placental vascular circulation as well as pregnancy outcomes, deserves further investigation.

Keywords: obesity, pregnancy, complications, weight gain

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Authors: Ndivhuho Tshikovhi

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The debate about indigenous people throughout the world has been necessitated by different circumstances that indigenous communities continue to suffer. Indigenous people of the world suffer chronic diseases, poor education, high unemployment and slow economic developments. This paper contributes to the continuous debate by studying the common elements of indigenous entrepreneur of the world and that of the South African indigenous entrepreneur. The research objective of this paper is to understand what constitute an indigenous status in the South African context as opposed to the indigenous people of the world. Furthermore, the study will explore the indigenous status through their entrepreneurial engagements. The paper will adopt a secondary data research method, by utilising the literature on indigenous entrepreneurship practice and theory of indigenous entrepreneurship. The implications of this paper is to bring about an African indigenous entrepreneurship debate rooted from the correct circumstances rather than generalised definitions. Recommendations for future research will be outlined, together with further readings on circumstantial evidence that necessitate indigenous entrepreneurs status in South Africa.

Keywords: indigenous entrepreneur, indigenous, entrepreneurship, indigenous people, entrepreneurship development

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Authors: Tae-Hoon Kim, Kwon-Ha Yoon, Hong Young Jun, Ki-Jong Kim, Young Hwan Lee, Myeung Su Lee, Keum Ha Choi, Ki Jung Yun, Eun Young Cho, Yong-Yeon Jeong, Chung-Hwan Jun

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Purpose: To assess the changes of hepatic metabolite for differentiation between non-alcoholic steatohepatitis (NASH) and simple steatosis on proton magnetic resonance spectroscopy (1H-MRS) in both humans and animal model. Methods: The local institutional review board approved this study and subjects gave written informed consent. 1H-MRS measurements were performed on a localized voxel of the liver using a point-resolved spectroscopy (PRESS) sequence and hepatic metabolites of alanine (Ala), lactate/triglyceride (Lac/TG), and TG were analyzed in NASH, simple steatosis and control groups. The group difference was tested with the ANOVA and Tukey’s post-hoc tests, and diagnostic accuracy was tested by calculating the area under the receiver operating characteristics (ROC) curve. The associations between metabolic concentration and pathologic grades or non-alcoholic fatty liver disease(NAFLD) activity scores were assessed by the Pearson’s correlation. Results: Patient with NASH showed the elevated Ala(p<0.001), Lac/TG(p < 0.001), TG(p < 0.05) concentration when compared with patients who had simple steatosis and healthy controls. The NASH patients were higher levels in Ala(mean±SEM, 52.5±8.3 vs 2.0±0.9; p < 0.001), Lac/TG(824.0±168.2 vs 394.1±89.8; p < 0.05) than simple steatosis. The area under the ROC curve to distinguish NASH from simple steatosis was 1.00 (95% confidence interval; 1.00, 1.00) with Ala and 0.782 (95% confidence interval; 0.61, 0.96) with Lac/TG. The Ala and Lac/TG levels were well correlated with steatosis grade, lobular inflammation, and NAFLD activity scores. The metabolic changes in human were reproducible to a mice model induced by streptozotocin injection and a high-fat diet. Conclusion: 1H-MRS would be useful for differentiation of patients with NASH and simple hepatic steatosis.

Keywords: non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, 1H MR spectroscopy, hepatic metabolites

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Authors: Marcela Dvorakova, Lenka Langhansova, Premysl Landa

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A series of quinazoline derivatives bearing aromatic rings in 2- and 4-positions were prepared and tested for their biological activity. Firstly, the compounds were evaluated for their potential to inhibit various kinases, such as autophagy activating kinase ULK1, 3-Phosphoinositide-dependent kinase 1, and TANK-binding kinase 1. None of the compounds displayed any activity on these kinases. Secondly, the compounds were tested for their anti-inflammatory activity expressed as cyclooxygenase (COX) isoforms and 5-lipoxygenase (5-LOX) inhibition. Three of the compounds showed significant selectivity towards COX-1 isoform (COX-2/COX-1 SI = 20-30). They inhibited COX-1 in a single-digit µM range. There was also one compound that exhibited inhibitory activity towards all three tested enzymes in µM range (IC50COX-1 = 1.9 µM; IC50COX-2 and 5-LOX = 10.1µM. COX-1 inhibition was until recently considered undesirable due to COX-1 constitutive expression in most cell types and tissues. Thus, there are not many compounds known with selective COX-1 activity. However, it is now believed that COX-1 plays an important role in the pathophysiology of several acute and chronic disorders, including cancer or neurodegenerative diseases. Thus, the discovery of effective COX-1 selective inhibitors is desirable and important.

Keywords: cyclooxygenases, kinases, lipoxygenases, quinazolines

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Authors: Farhad Fakoursevom

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Heart disease is one of the diseases which is found in abundance today. Various types of surgeries, such as bypasses, angiography, angioplasty, etc., are used to treat patients. People may receive such surgeries, some of which are invasive and some non-invasive, throughout their lives. People might cope with pre-surgery anxiety and stress, which can disrupt their normal life and even reduce the effects of the surgery, so the desired result can not be achieved in surgery. Considering this issue, the present study aimed to do a comparative assessment of people who received sedatives before surgery and people who did not receive sedatives. In terms of the purpose, this is an applied research and descriptive survey in terms of method. The statistical population included patients who underwent surgeries in the specialist heart hospitals of Mashhad, Iran; 60 people were considered as a statistical population, 30 of them received sedatives before surgery, and 30 others had not received sedatives before surgery. Valid and up-to-date articles were systematically used to collect theoretical bases, and a researcher-made questionnaire was used to examine the level of stress and anxiety of people. The questionnaire content validity was assessed by a panel of experts in psychology and medicine. The construct validity was tested using the software. Cronbach's alpha and composite reliability were used for reliability, which shows the appropriate reliability of the questionnaire. SPSS software was used to compare the research results between two groups, and the research findings showed that there is no significant association between the people who received sedatives and those who did not receive sedatives in terms of the amount of stress and anxiety. The longer the time of taking the drugs before the surgery, the more the mental peace of the patients will be. According to the results, it can be said that if we don't need to have an emergency operation and need more time, we have to use sedative drugs with different doses compared to the severity of the surgery, and also in case of a medical emergency such as heart surgery due to a stroke, we have to take advantage of psychological services during and before the operation and sedative drugs so that the patients can control their stress and anxiety and achieve better outcomes.

Keywords: sedative drugs, stress, anxiety, surgery

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Authors: Linyi Fan, C.J. Schumaker

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Background: Biomedical efforts to treat Alzheimer’s disease (AD) have typically produced mixed to poor results, while more lifestyle-focused treatments such as exercise may fare better than existing biomedical treatments. A few promising studies have indicated that activities of daily life (ADL) may be a useful way of predicting AD. However, the existing cross-sectional studies fail to show how functional-related issues such as ADL in early years predict AD and how social factors influence health either in addition to or in interaction with individual risk factors. This study would helpbetterscreening and early treatments for the elderly population and healthcare practice. The findings have significance academically and practically in terms of creating positive social change. Methodology: The purpose of this quantitative historical, correlational study was to examine the relationship between early years’ ADL and the development of AD in later years. The studyincluded 4,526participantsderived fromRAND HRS dataset. The Health and Retirement Study (HRS) is a longitudinal household survey data set that is available forresearchof retirement and health among the elderly in the United States. The sample was selected by the completion of survey questionnaire about AD and dementia. The variablethat indicates whether the participant has been diagnosed with AD was the dependent variable. The ADL indices and changes in ADL were the independent variables. A four-step multilevel regression model approach was utilized to address the research questions. Results: Amongst 4,526 patients who completed the AD and dementia questionnaire, 144 (3.1%) were diagnosed with AD. Of the 4,526 participants, 3,465 (76.6%) have high school and upper education degrees,4,074 (90.0%) were above poverty threshold. The model evaluatedthe effect of ADL and change in ADL on onset of AD in late years while allowing the intercept of the model to vary by level of education. The results suggested that the only significant predictor of the onset of AD was changes in early years’ ADL (b = 20.253, z = 2.761, p < .05). However, the result of the sensitivity analysis (b = 7.562, z = 1.900, p =.058), which included more control variables and increased the observation period of ADL, are not supported this finding. The model also estimated whether the variances of random effect vary by Level-2 variables. The results suggested that the variances associated with random slopes were approximately zero, suggesting that the relationship between early years’ ADL were not influenced bysociodemographic factors. Conclusion: The finding indicated that an increase in changes in ADL leads to an increase in the probability of onset AD in the future. However, this finding is not support in a broad observation period model. The study also failed to reject the hypothesis that the sociodemographic factors explained significant amounts of variance in random effect. Recommendations were then made for future research and practice based on these limitations and the significance of the findings.

Keywords: alzheimer’s disease, epidemiology, moderation, multilevel modeling

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Authors: Pouya Karimi, Ramin Ghasemi Shayan

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Conclusions of the sort and setting of observational treatment for immunocompromised patients with fever are confused by the qualities of the hidden disease and the impacts of medications previously got, just as by changing microbiological examples and patterns in sedate obstruction at national and institutional levels. A few frameworks have been proposed to recognize patients who could profit by outpatient anti-infection treatment from patients who require hospitalization. Useful contemplations may choose whether the fundamental checking during the time of neutropenia can be accomplished.

Keywords: microbiology, infectious, neutropenia, epidemiology

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Authors: Areej Makeineldein Mustafa

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The study evaluates the management processes and healthcare provider compliance with the National Institute for Health and Care Excellence recommendations for constipation management. We aimed to evaluate the adherence to National Institute for Health and Care Excellence guidelines in the management of constipation during the period from February to June 2023. We collected data from a random sample ( 51 patients) over 4 months with inclusion criteria for patients above 60 who were just admitted to the care of the elderly department during this period. Patient age, sex, medical records for constipation, acute or chronic constipation, or opioid-induced constipation, and treatment options were used to identify constipation and the type of treatment given. Our findings indicate that there is a gap between practice and National Institute for Health and Care Excellence guideline steps; only 3 patient was given medications according to National Institute for Health and Care Excellence guidelines in order of combination or steps of escalation. Addressing these gaps could potentially lead to enhanced patient outcomes and an overall improvement in the quality of care provided to individuals suffering from constipation.

Keywords: constipation, elderly, management, patient

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Authors: Mohammad Karam, Abdulmalik Alsaif, Abdulrahman Al-Naseem, Amrit Hayre, Abdurrahman Al Jabbouri, Ahmad Aldubaikhi, Narvair Kahlar, Salem Al-Mutairi

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Purpose: To compare the outcomes of mycophenolate mofetil (MMF) versus methotrexate (MTX) in non-infectious ocular inflammatory disease (NIOID). Methods: A systematic review and meta-analysis were performed as per the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines and an electronic search was conducted to identify all comparative studies of MMF versus MTX in NIOID. Treatment results and side effects were primary outcome measures. Secondary outcome measures included visual acuity and resolution of macular oedema. Fixed and random-effects models were used for the analysis. Results: Four studies enrolling 905 patients were identified. There was no significant difference between MMF and MTX groups in overall treatment success (Odds Ratio [OR] = 0.97, P = 0.96) and failure (OR = 0.86, P = 0.85) of NIOID. Although treatment success of uveitis showed no significant difference for anterior and intermediate uveitis cases (OR = 2.33, P = 0.14), MTX showed a significantly improved effect in cases involving posterior uveitis and panuveitis (OR = 0.41, P = 0.003). However, the median dose required for treatment success was lower for MTX whereas MMF was associated with a faster median time to treatment success. Further to this, MMF showed a reduced rate of side effects when compared to MTX, but MTX failed to reach statistical significance, most notably for liver enzyme elevation (OR = 0.65, P = 0.16), fatigue (OR = 0.84, P = 0.49) and headache (OR = 0.81, P = 0.37). For secondary outcomes, no significant difference was noted in visual acuity and resolution of macular edema. Conclusions: MMF is comparable to MTX in the treatment of NIOID as there was no significant difference in the outcome of treatment success and side effect profiles.

Keywords: Mycophenolate mofetil, methotrexate, non-infectious ocular inflammation, uveitis, scleritis

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Authors: Sadia Imran, Zenab Naseem

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Dengue fever is one of the most alarming mosquito-borne viral diseases. Dengue virus has been distributed over the years exponentially throughout the world be it tropical or sub-tropical regions of the world, particularly in the last ten years. Changing topography, climate change in terms of erratic seasonal trends, rainfall, untimely monsoon early or late and longer or shorter incidences of either summer or winter. Globalization, frequent travel throughout the world and viral evolution has lead to more severe forms of Dengue. Global incidence of dengue infections per year have ranged between 50 million and 200 million; however, recent estimates using cartographic approaches suggest this number is closer to almost 400 million. In recent years, Pakistan experienced a deadly outbreak of the disease. The reason could be that they have the maximum exposure outdoors. Public organizations have observed that changing climate, especially lower average summer temperature, and increased vegetation have created tropical-like conditions in the city, which are suitable for Dengue virus growth. We will conduct a time-series analysis to study the interrelationship between dengue incidence and diurnal ranges of temperature and humidity in Pakistan, Lahore being the main focus of our study. We have used annual data from 2005 to 2015. We have investigated the relationship between climatic variables and dengue incidence. We used time series analysis to describe temporal trends. The result shows rising trends of Dengue over the past 10 years along with the rise in temperature & rainfall in Lahore. Hence this seconds the popular statement that the world is suffering due to Climate change and Global warming at different levels. Disease outbreak is one of the most alarming indications of mankind heading towards destruction and we need to think of mitigating measures to control epidemic from spreading and enveloping the cities, countries and regions.

Keywords: Dengue, epidemic, globalization, climate change

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Authors: Abu Salim Mustafa

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Brucellosis is a zoonotic disease endemic in Kuwait. Human brucellosis can be caused by several Brucella species with Brucella melitensis causing the most severe and Brucella abortus the least severe disease. Furthermore, relapses are common after successful chemotherapy of patients. The classical biochemical methods of culture and serology for identification of Brucellae provide information about the species and serotypes only. However, to differentiate between relapse and reinfection/epidemiological investigations, the identification of genotypes using molecular methods is essential. In this study, four molecular methods [16S rRNA gene sequencing, real-time PCR, enterobacterial repetitive intergenic consensus (ERIC)-PCR and multilocus variable-number tandem-repeat analysis (MLVA)-16] were evaluated for the identification and typing of 75 strains of Brucella isolated in Kuwait. The 16S rRNA gene sequencing suggested that all the strains were B. melitensis and real-time PCR confirmed their species identity as B. melitensis. The ERIC-PCR band profiles produced a dendrogram of 75 branches suggesting each strain to be of a unique type. The cluster classification, based on ~ 80% similarity, divided all the ERIC genotypes into two clusters, A and B. Cluster A consisted of 9 ERIC genotypes (A1-A9) corresponding to 9 individual strains. Cluster B comprised of 13 ERIC genotypes (B1-B13) with B5 forming the largest cluster of 51 strains. MLVA-16 identified all isolates as B. melitensis and divided them into 71 MLVA-types. The cluster analysis of MLVA-16-types suggested that most of the strains in Kuwait originated from the East Mediterranean Region, a few from the African group and one new genotype closely matched with the West Mediterranean region. In conclusion, this work demonstrates that B. melitensis, the most pathogenic species of Brucella, is prevalent in Kuwait. Furthermore, MLVA-16 is the best molecular method, which can identify the Brucella species and genotypes as well as determine their origin in the global context. Supported by Kuwait University Research Sector grants MI04/15 and SRUL02/13.

Keywords: Brucella, ERIC-PCR, MLVA-16, RT-PCR, 16S rRNA gene sequencing

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