Clinical and neurogenetic characterisation of autosomal recessive RBL2-associated progressive neurodevelopmental disorder.

Retinoblastoma (RB) proteins are highly conserved transcriptional regulators that play important roles during development by regulating cell-cycle gene expression. RBL2 dysfunction has been linked to a severe neurodevelopmental disorder. However, to date, clinical features have only been described in six individuals carrying five biallelic predicted loss of function (pLOF) variants. To define the phenotypic effects of RBL2 mutations in detail, we identified and clinically characterized a cohort of 28 patients from 18 families carrying LOF variants in RBL2 , including fourteen new variants that substantially broaden the molecular spectrum. The clinical presentation of affected individuals is characterized by a range of neurological and developmental abnormalities. Global developmental delay and intellectual disability were uniformly observed, ranging from moderate to profound and involving lack of acquisition of key motor and speech milestones in most patients. Frequent features included postnatal microcephaly, infantile hypotonia, aggressive behaviour, stereotypic movements and non-specific dysmorphic features. Common neuroimaging features were cerebral atrophy, white matter volume loss, corpus callosum hypoplasia and cerebellar atrophy. In parallel, we used the fruit fly, Drosophila melanogaster , to investigate how disruption of the conserved RBL2 orthologueue Rbf impacts nervous system function and development. We found that Drosophila Rbf LOF mutants recapitulate several features of patients harboring RBL2 variants, including alterations in the head and brain morphology reminiscent of microcephaly, and perturbed locomotor behaviour. Surprisingly, in addition to its known role in controlling tissue growth during development, we find that continued Rbf expression is also required in fully differentiated post-mitotic neurons for normal locomotion in Drosophila , and that adult-stage neuronal re-expression of Rbf is sufficient to rescue Rbf mutant locomotor defects. Taken together, this study provides a clinical and experimental basis to understand genotype-phenotype correlations in an RBL2 -linked neurodevelopmental disorder and suggests that restoring RBL2 expression through gene therapy approaches may ameliorate aspects of RBL2 LOF patient symptoms.

Teicoplanin associated gene tcaA inactivation increases persister cell formation in Staphylococcus aureus.

Staphylococcus aureus is part of normal human flora and is widely associated with hospital-acquired bacteremia. S. aureus has shown a diverse array of resistance to environmental stresses and antibiotics. Methicillin-resistant S. aureus (MRSA) is on the high priority list of new antibiotics discovery and glycopeptides are considered the last drug of choice against MRSA. S. aureus has developed resistance against glycopeptides and the emergence of vancomycin-intermediate-resistant, vancomycin-resistant, and teicoplanin-resistant strains is globally reported. Teicoplanin-associated genes tcaR-tcaA-tcaB (tcaRAB) is known as the S. aureus glycopeptide resistance operon that is associated with glycopeptide resistance. Here, for the first time, the role of tcaRAB in S. aureus persister cells formation, and ΔtcaA dependent persisters' ability to resuscitate the bacterial population was explored. We recovered a clinical strain of MRSA from a COVID-19 patient which showed a high level of resistance to teicoplanin, vancomycin, and methicillin. Whole genome RNA sequencing revealed that the tcaRAB operon expression was altered followed by high expression of glyS and sgtB. The RNA-seq data revealed a significant decrease in tcaA (p = 0.008) and tcaB (p = 0.04) expression while tcaR was not significantly altered. We knocked down tcaA, tcaB, and tcaR using CRISPR-dCas9 and the results showed that when tcaA was suppressed by dCas9, a significant increase was witnessed in persister cells while tcaB suppression did not induce persistence. The results were further evaluated by creating a tcaA mutant that showed ΔtcaA formed a significant increase in persisters in comparison to the wild type. Based on our findings, we concluded that tcaA is the gene that increases persister cells and glycopeptide resistance and could be a potential therapeutic target in S. aureus.

The functional repertoire of AmpR in the AmpC ß-lactamase high expression and decreasing ß-lactam and aminoglycosides resistance in ESBL Citrobacter freundii.

Citrobacter freundii is characterized by AmpC ß-lactamases that develop resistance to ß-lactam antibiotics. The production of extended-spectrum ß-lactamase (ESBL) is substantially high in Escherichia coli, C. freundii, Enterobacter cloacae, and Serratia marcescens, but infrequently explored in C. freundii. The present investigation characterized the ESBL C. freundii and delineated the genes involved in decrease in antibiotics resistance. We used the VITEK-2 system and Analytical Profile Index (API) kit to characterize and identify the Citrobacter isolates. The mRNA level of AmpC and AmpR was determined by RT-qPCR, and gel-shift assay was performed to evaluate protein-DNA binding. Here, a total of 26 Citrobacter strains were isolated from COVID-19 patients that showed varying degrees of antibiotic resistance. We examined and characterized the multidrug resistant C. freundii that showed ESBL production. The RT-qPCR analysis revealed that the AmpC mRNA expression is significantly high followed by a high level of AmpR. We sequenced the AmpC and AmpR genes that revealed the AmpR has four novel mutations in comparison to the reference genome namely; Thr64Ile, Arg86Ser, Asp135Val, and Ile183Leu while AmpC remained intact. The ΔAmpR mutant analysis revealed that the AmpR positively regulates oxidative stress response and decreases ß-lactam and aminoglycosides resistance. The AmpC and AmpR high expression was associated with resistance to tazobactam, ampicillin, gentamicin, nitrofurantoin, and cephalosporins whereas AmpR deletion reduced ß-lactam and aminoglycosides resistance. We conclude that AmpR is a positive regulator of AmpC that stimulates ß-lactamases which inactivate multiple antibiotics.

Recent developments in natural biopolymer based drug delivery systems.

Targeted delivery of drug molecules to diseased sites is a great challenge in pharmaceutical and biomedical sciences. Fabrication of drug delivery systems (DDS) to target and/or diagnose sick cells is an effective means to achieve good therapeutic results along with a minimal toxicological impact on healthy cells. Biopolymers are becoming an important class of materials owing to their biodegradability, good compatibility, non-toxicity, non-immunogenicity, and long blood circulation time and high drug loading ratio for both macros as well as micro-sized drug molecules. This review summarizes the recent trends in biopolymer-based DDS, forecasting their broad future clinical applications. Cellulose chitosan, starch, silk fibroins, collagen, albumin, gelatin, alginate, agar, proteins and peptides have shown potential applications in DDS. A range of synthetic techniques have been reported to design the DDS and are discussed in the current study which is being successfully employed in ocular, dental, transdermal and intranasal delivery systems. Different formulations of DDS are also overviewed in this review article along with synthesis techniques employed for designing the DDS. The possibility of these biopolymer applications points to a new route for creating unique DDS with enhanced therapeutic qualities for scaling up creative formulations up to the clinical level.

Eco-friendly textile desizing with indigenously produced amylase from Bacillus cereus AS2.

Starch is added to the fabric surface to secure weaving process. During finishing these sized particles are removed from the fabric and prepared it for printing and dyeing. Chemicals de-sizing agents damage fabric surfaces and reduce the quality of the product. An alternative to these conventional desizing agents is the use of biological molecules i.e. enzymes. The current study compares traditional de-sizing to bio-based de-sizing methods, as well as the optimization of fabric desizing settings using crude amylase. Amylase-producing Bacillus cereus AS2 was isolated from indigenous soil samples. The maximal fermentative de-sizing capability was discovered at 72 h, with no fabric surface degradation. Chemical desizing showed that the fabric lost all sizing agents to TEGEWA scale 9 within 1 h in presence of 5N HCl. Optimal studies for desizing showed that 1000 IU/ml of amylase resulted in maximum de-sizing within 15 h at 60 °C and 0.5% Triton-X. Water absorbance and weight loss, both parameters were used to check the desizing efficacy and it was found that de-sizing to same scale was occurred in the case of enzyme as well as commercially desized fabric. Enzyme desized cloth was found to be free of any starch particles in SEM micrographs, identical to industrially de-sized fabric, ensuring bioprocess efficacy.

Study on awareness, knowledge, and practices towards antibiotic use among the educated and uneducated people of Khyber Pakhtunkhwa Province, Pakistan

INTRODUCTION: Antimicrobial resistance developed through the inadequate use of antibiotics; is an overriding task for global public health. OBJECTIVE: To explore awareness, knowledge, and practices, and compare the elements associated with antibiotic misuse in different University students and uneducated people of Khyber Pakhtunkhwa Province, Pakistan. METHODS: Cross-sectional study was conducted from July to December 2020 using a validated questionnaire. Data were collected from eleven different university students and uneducated people of Khyber Pakhtunkhwa, Pakistan. RESULTS: 3,600 questionnaires were completed, consisting of 56.9% Male and 43.0% Female. 1,999 (55.5%) of the antibiotic users reported through the survey used non-prescription antibiotics within a one-month study period. Out of the participants, 230 (6.3%) were uneducated or their education level was below matric rest were university students. 1999 (55.5%) reported buying Antibiotics with Medical Prescription. Most self-medicated participants (56.9%) stop taking antibiotics when they feel better. More than 90% of the respondents answered that doctors and pharmacist staff do not guide them well that how to use antibiotics. 2,171 (60.03%) respondents mistakenly believed that antibiotics improve restoration from coughs and colds. Only 720 (20%) respondents knew that antibiotics also disturb normal flora and 547 participants (15.9%) agree that unnecessary use of antibiotics causes bacterial resistance. CONCLUSION: Finding from this study may have important implications for public health policy in Khyber Pakhtunkhwa, Pakistan given the growing global resistance to antibiotics and the reported health issues related to their improper use.

Myogenesis and Analysis of Antimicrobial Potential of Silver Nanoparticles (AgNPs) against Pathogenic Bacteria.

The widespread and indiscriminate use of broad-spectrum antibiotics leads to microbial resistance, which causes major problems in the treatment of infectious diseases. However, advances in nanotechnology have opened up new domains for the synthesis and use of nanoparticles against multidrug-resistant pathogens. The traditional approaches for nanoparticle synthesis are not only expensive, laborious, and hazardous but also have various limitations. Therefore, new biological approaches are being designed to synthesize economical and environmentally friendly nanoparticles with enhanced antimicrobial activity. The current study focuses on the isolation, identification, and screening of metallotolerant fungal strains for the production of silver nanoparticles, using antimicrobial activity analysis and the characterization of biologically synthesized silver nanoparticles by X-ray diffraction (XRD) spectroscopy, energy-dispersive X-ray spectroscopy (EDX), and scanning electron microscopy (SEM). In total, 11 fungal isolates were isolated and screened for the synthesis of AgNPs, while the Penicillium notatum (K1) strain was found to be the most potent, demonstrating biosynthetic ability. The biologically synthesized silver nanoparticles showed excellent antibacterial activity against the bacteria Escherichia coli (ATCC10536), Bacillus subtilis, Staphylococcus aureus (ATCC9144), Pseudomonas aeruginosa (ATCC10145), Enterococcus faecalis, and Listeria innocua (ATCC13932). Furthermore, three major diffraction peaks in the XRD characterization, located at the 2θ values of 28.4, 34.8, 38.2, 44, 64, and 77°, confirmed the presence of AgNPs, while elemental composition analysis via EDX and spherical surface topology with a scanning electron microscope indicated that its pure crystalline nature was entirely composed of silver. Thus, the current study indicates the enhanced antibacterial capability of mycologically synthesized AgNPs, which could be used to counter multidrug-resistant pathogens.

Potential of mineral-solubilizing bacteria for physiology and growth promotion of Chenopodium quinoa Willd.

Nutrient deficiency in wild plant species, including quinoa (Chenopodium quinoa Willd), can be overcome by applying mineral-solubilizing bacteria. Quinoa is a gluten-free, nutritious food crop with unique protein content. The present study aimed to characterize mineral-solubilizing rhizobacterial strains and to evaluate their plant growth-promoting potential in quinoa seedlings. More than sixty rhizobacterial strains were isolated from the quinoa rhizosphere and found eighteen strains to be strong phosphate solubilizers. Most of these bacterial strains showed zinc solubilization, and more than 80% of strains could solubilize manganese. The selected strains were identified as Bacillus altitudinis Cq-3, Pseudomonas flexibilis Cq-32, Bacillus pumilus Cq-35, Pseudomonas furukawaii Cq-40, Pontibacter lucknowensis Cq-48, and Ensifer sp. Cq-51 through 16S rRNA partial gene sequencing. Mainly, these strains showed the production of organic acids, including malic, gluconic, tartaric, ascorbic, lactic, and oxalic acids in insoluble phosphorus amended broth. All strains showed production of gluconic acids, while half of the strains could produce malic, ascorbic, lactic, and oxalic acids. These strains demonstrated the production of indole-3-acetic acid in the presence as well as in the absence of L-tryptophan. The bacterial strains also demonstrated their ability to promote growth and yield attributes, including shoot length, root length, leave numbers, root and shoot dry biomass, spike length, and spikes numbers of quinoa in pots and field trials. Increased physiological attributes, including relative humidity, quantum flux, diffusive resistance, and transpiration rate, were observed due to inoculation with mineral solubilizing bacterial strains under field conditions. P. lucknowensis Cq-48, followed by P. flexibilis Cq-32, and P. furukawaii Cq-40 showed promising results to promote growth, yield, and physiological attributes. The multi-traits characteristics and plant growth-promoting ability in the tested bacterial strains could provide an opportunity for formulating biofertilizers that could promote wild quinoa growth and physiology.

High-Molecular-Weight Dextran-Type Exopolysaccharide Produced by the Novel Apilactobacillus waqarii Improves Metabolic Syndrome: In Vitro and In Vivo Analyses.

Metabolic syndrome is a leading medical concern that affects one billion people worldwide. Metabolic syndrome is defined by a clustering of risk factors that predispose an individual to cardiovascular disease, diabetes and stroke. In recent years, the apparent role of the gut microbiota in metabolic syndrome has drawn attention to microbiome-engineered therapeutics. Specifically, lactic acid bacteria (LAB) harbors beneficial metabolic characteristics, including the production of exopolysaccharides and other microbial byproducts. We recently isolated a novel fructophilic lactic acid bacterium (FLAB), Apilactobacillus waqarii strain HBW1, from honeybee gut and found it produces a dextran-type exopolysaccharide (EPS). The objective of this study was to explore the therapeutic potential of the new dextran in relation to metabolic syndrome. Findings revealed the dextran's ability to improve the viability of damaged HT-29 intestinal epithelial cells and exhibit antioxidant properties. In vivo analyses demonstrated reductions in body weight gain and serum cholesterol levels in mice supplemented with the dextran, compared to control (5% and 17.2%, respectively). Additionally, blood glucose levels decreased by 16.26% following dextran supplementation, while increasing by 15.2% in non-treated mice. Overall, this study displays biotherapeutic potential of a novel EPS to improve metabolic syndrome and its individual components, warranting further investigation.

Response Surface Methodology for Optimization of Operational Parameters To Remove Ciprofloxacin from Contaminated Water in the Presence of a Bacterial Consortium.

Ciprofloxacin (CFX) is a broad-spectrum fluoroquinolone antibiotic that is widely used to treat bacterial infections in humans and other animals. However, its unwanted occurrence in any (eco)system can affect nontarget bacterial communities, which may also impair the performance of the natural or artificially established bioremediation system. The problem could be minimized by optimization of operational parameters via modeling of multifactorial tests. To this end, we used a Box-Behnken design in response surface methodology (RSM) to generate the experimental layout for testing the effect of the CFX biodegradation for four important parameters, that is, temperature (°C), pH, inoculum size (v/v %), and CFX concentration (mg L-1). For inoculation, a consortium of three bacterial strains, namely, Acenitobacter lwofii ACRH76, Bacillus pumilus C2A1, and Mesorihizobium sp. HN3 was used to degrade 26 mg L-1 of CFX. We found maximum degradation of CFX (98.97%; initial concentration of 25 mg L-1) at 2% inoculum size, 7 pH, and 35 °C of temperature in 16 days. However, minimum degradation of CFX (48%; initial concentration of 50 mg L-1) was found at pH 6, temperature 30 °C, and inoculum size 1%. Among different tested parameters, pH appears to be the main limiting factor for CFX degradation. Independent factors attributed 89.37% of variation toward CFX degradation as revealed by the value of the determination coefficient, that is, R 2 = 0.8937. These results were used to formulate a mathematical model in which the computational data strongly correlated with the experimental results. This study showcases the importance of parameter optimization via RSM for any bioremediation studies particularly for antibiotics in an economical, harmless, and eco-friendly manner.

Pathophysiology of Methicillin-Resistant Staphylococcus aureus Superinfection in COVID-19 Patients.

The global spread of the coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), has infected humans in all age groups, deteriorated host immune responses, and caused millions of deaths. The reasons for individuals succumbing to COVID-19 were not only the SARS-CoV-2 infection but also associated bacterial infections. Antibiotics were largely used to prevent bacterial infections during COVID-19 illness, and many bacteria became resistant to conventional antibiotics. Although COVID-19 was considered the main culprit behind the millions of deaths, bacterial coinfections and superinfections were the major factors that increased the mortality rate in hospitalized patients. In the present study, we assessed the pathophysiology of methicillin-resistant Staphylococcus aureus (MRSA) superinfection in COVID-19 patients in Pakistan. A total of 3492 COVID-19 hospitalized patients were screened among which 224 strain were resistant to methicillin; 110 strains were tazobactam-resistant; 53 strains were ciprofloxacin-resistant; 23 strains were gentamicin-resistant; 11 strains were azithromycin-resistant; 3 strains were vancomycin-resistant. A high frequency of MRSA was detected in patients aged ≥50 with a prevalence of 7.33%, followed by patients aged >65 with a prevalence of 5.48% and a 5.10% prevalence in patients aged <50. In addition, pneumonia was detected in the COVID-19-associated MRSA (COVID-MRSA) that showed decreased levels of lymphocytes and albumin and increased the mortality rate from 2.3% to 25.23%. Collectively, an MRSA superinfection was associated with increased mortality in COVID-19 after 12 to 18 days of hospitalization. The study assessed the prevalence of MRSA, mortality rate, pneumonia, and the emergence of antibiotic resistance as the main outcomes. The study summarized that COVID-MRSA aggravated the treatment and recovery of patients and suggested testing MRSA as critical for hospitalized patients.

Effect of ellagic acid and mesocarp extract of Punica granatum on productive and reproductive performances of laying hens.

In the present study, we determined the potential effects of ellagic acid and mesocarp extract of Punica granatum on the productive and reproduction performance of laying hens. Five treatment groups were setup: (1) control group (without ellagic acid), (2) 50 mg of ellagic acid, (3) 100 mg of ellagic acid, (4) 200 mg of ellagic acid, and (5) mesocarp extract of P. granatum. All the groups were investigated for feed intake, body weight, egg production, egg quality, fertility, hatchability, antioxidant status of serum and liver, lipid peroxidation, and antibacterial activities. Egg production, feed intake, and bodyweight were significantly increased (p < 0.05) with 100 mg of ellagic acid and P. granatum extract while no significant effect was observed on albumen and yolk weight, yolk index, yolk color, egg-shape index, and Haugh unit. Both ellagic acid and P. granatum extract significantly improved hatchability while 100 and 200 mg/kg of ellagic acid numerically decreased fertility. Besides, ellagic acid (100 mg/kg) and P. granatum extract significantly decreased malondialdehyde concentration and increased total antioxidant capacity, glutathione peroxidase, and total superoxide dismutase in serum and liver samples of laying hens (p < 0.05). The lipid peroxidation was decreased among the treatment groups, with 100 mg of ellagic acid and P. granatum extract showed the best activity. Moreover, ellagic acid demonstrated strong killing activity against Escherichia coli and Staphylococcus aureus while it was ineffective against methicillin-resistant S. aureus. Our results conclude that ellagic acid and P. granatum promoted egg production, hatchability, and antioxidant enzyme activities of the laying hens.

Production of bimodal molecular weight levan by a Lactobacillus reuteri isolate from fish gut.

An exopolysaccharide (EPS) synthesizing potentially probiotic Gram-positive bacterial strain was isolated from fish (Tor putitora) gut, and its EPS was structurally characterized. The isolate, designated as FW2, was identified as Lactobacillus reuteri through 16S rRNA gene sequencing and phylogenetic analysis. This isolate produces fructan-type EPS using sucrose as a substrate. Based on 13C-NMR spectroscopy, methylation analysis and monosaccharide composition, the EPS was identified as a linear levan polymer with fructose as main constituent linked via ß(2 → 6) linkages. Based on molecular weight (MW) distribution, two groups of levan were found to be produced by the isolate FW2: one with high MW (4.6 × 106 Da) and the other having much lower MW (1.2 × 104 Da). The isolate yielded about 14 g/L levan under optimized culturing parameters including aeration conditions, pH, temperature and substrate concentration. The obtained bimodal molecular weight linear levan is the first of its type to be synthesized by a L. reuteri isolate from fish gut. Bimodal molecular weight prebiotic levan together with the probiotic potential of the producing strain would provide a new promising synbiotic combination for use in aqua culture.

Bi-allelic variants in OGDHL cause a neurodevelopmental spectrum disease featuring epilepsy, hearing loss, visual impairment, and ataxia.

The 2-oxoglutarate dehydrogenase-like (OGDHL) protein is a rate-limiting enzyme in the Krebs cycle that plays a pivotal role in mitochondrial metabolism. OGDHL expression is restricted mainly to the brain in humans. Here, we report nine individuals from eight unrelated families carrying bi-allelic variants in OGDHL with a range of neurological and neurodevelopmental phenotypes including epilepsy, hearing loss, visual impairment, gait ataxia, microcephaly, and hypoplastic corpus callosum. The variants include three homozygous missense variants (p.Pro852Ala, p.Arg244Trp, and p.Arg299Gly), three compound heterozygous single-nucleotide variants (p.Arg673Gln/p.Val488Val, p.Phe734Ser/p.Ala327Val, and p.Trp220Cys/p.Asp491Val), one homozygous frameshift variant (p.Cys553Leufs∗16), and one homozygous stop-gain variant (p.Arg440Ter). To support the pathogenicity of the variants, we developed a novel CRISPR-Cas9-mediated tissue-specific knockout with cDNA rescue system for dOgdh, the Drosophila ortholog of human OGDHL. Pan-neuronal knockout of dOgdh led to developmental lethality as well as defects in Krebs cycle metabolism, which was fully rescued by expression of wild-type dOgdh. Studies using the Drosophila system indicate that p.Arg673Gln, p.Phe734Ser, and p.Arg299Gly are severe loss-of-function alleles, leading to developmental lethality, whereas p.Pro852Ala, p.Ala327Val, p.Trp220Cys, p.Asp491Val, and p.Arg244Trp are hypomorphic alleles, causing behavioral defects. Transcript analysis from fibroblasts obtained from the individual carrying the synonymous variant (c.1464T>C [p.Val488Val]) in family 2 showed that the synonymous variant affects splicing of exon 11 in OGDHL. Human neuronal cells with OGDHL knockout exhibited defects in mitochondrial respiration, indicating the essential role of OGDHL in mitochondrial metabolism in humans. Together, our data establish that the bi-allelic variants in OGDHL are pathogenic, leading to a Mendelian neurodevelopmental disease in humans.

Autism - A Comprehensive Array of Prominent Signs and Symptoms.

BACKGROUND: Autism Spectrum Disorder (ASD) is a multifaceted neurodevelopmental condition characterized by multiple psychological and physiological impairments in young children. According to the recent reports, 1 out of every 58 newly-born children is suffering from autism. The aetiology of the disorder is complex and poorly understood, hindering the adaptation of targeted and effective therapies. There are no well- established diagnostic biomarkers for autism. Hence the analysis of symptoms by the pediatricians plays a critical role in the early intervention. METHODS: In the present report, we have emphasized 24 behavioral, psychological and clinical symptoms of autism. RESULTS: Impaired social interaction, restrictive and narrow interests, anxiety, depression; aggressive, repetitive, rigid and self-injurious behavior, lack of consistency, short attention span, fear, shyness and phobias, hypersensitivity and rapid mood alterations, high level of food and toy selectivity; inability to establish friendships or follow the instructions; fascination by round spinning objects and eating non-food materials are common psychological characteristics of autism. Speech or hearing impairments, poor cognitive function, gastrointestinal problems, weak immunity, disturbed sleep and circadian rhythms, weak motor neuromuscular interaction, lower level of serotonin and neurotransmitters, headache and body pain are common physiological symptoms. CONCLUSION: A variable qualitative and quantitative impact of this wide range of symptoms is perceived in each autistic individual, making him/her distinct, incomparable and exceptional. Selection and application of highly personalized medical and psychological therapies are therefore recommended for the management and treatment of autism.

Prevalence and risk factors of hepatitis B and C viruses among haemodialysis patients: a multicentric study.

BACKGROUND: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are important causes of morbidity and mortality among haemodialysis (HD) patients and create problems in the management of patients in the renal dialysis units, as patients with chronic renal failure do not absolutely clear these viral infections. AIM: The aim of the study is molecular detection of HBV and HCV and their possible risk factors among the HD patients in northern Pakistan. MATERIALS AND METHODS: A cross-sectional study was conducted from November 2013 to June 2014. The infections were investigated through serological and molecular techniques. RESULTS: The overall prevalence of HBV among the five HD centres was 7.5%. The main risk factors were HD centre (26.66%), history of blood transfusion (20%), dental procedure (13.33%) and time duration on HD (6.66%). However, the overall prevalence of HCV among the five HD centres was 19.58%. The main risk factors included HD centre (25.53%), history of blood transfusion (25.53%), dental procedure (10.64%), surgical treatment (6.38%), patients treated abroad (6.38%) and time duration on HD (4.25%). CONCLUSION: The high prevalence of hepatitis viruses among HD patients of northern Pakistan indicates a close relation between HD centres and hepatitis virus transmission. Therefore, preventive control measures are essential to reduce hepatitis transmission in HD centres.

Antibiotic susceptibility profile of bacterial isolates from post-surgical wounds of patients in tertiary care hospitals of Peshawar, Pakistan.

Postoperative wound infections are the infections of the operating site within thirty days after surgery. The infections that develop after surgery are a major problem throughout the world leading to, increased morbidity and mortality. This study was carried out to determine the prevalence of bacterial pathogens causing wound infection in the surgical wards and to determine the antimicrobial sensitivity patterns of the isolated bacteria. A total of 250 wound samples were collected over a period of 6 months from July-December, 2016. The pathogenic bacteria were isolated, identified and their antibiotic susceptibility was determined through disc diffusion method. Among 250 cases, 210 (84%) were culture positive for bacterial pathogens, while 40 (16%) were bacteriologically sterile (Negative). Rate of infection was high in males (55.6%) than females (44.4%). The predominant isolates were E.coli 55 (26.19%), followed by S.aureus 51 (24.28%), Pseudomonas spp. 43(20.47%), S.aureus MRSA 21 (10%), Proteus Marbillis 15 (7.14%), E.coli ESBL producer was 8 (3.81%), Acinetobacter 7 (3.33%) Proteus valgaris 5 (2.38%), b-Streptococci 3 (1.43%) and Klebsella pneumonia were the least, 2 (0.95%). Linezolid, Vancomycin, Amoxycillin, Cefoperazone and Meropenem are the most effective antibiotics for treating post-surgical wound infections.

Scorpion Venom Peptides as a Potential Source for Human Drug Candidates.

BACKGROUND: Scorpion venom is the most expensive and deadly venom with exciting medical prospects and having a potential as a source of drug candidates. A number of scorpion venom peptides have shown promising site specificity and are involved in the regulation of biological mechanisms. Due to the structural and functional specificity, the scorpion peptides are widely used for the development of specific drugs especially for the cardiovascular and other immune diseases. In this review, we summarize scorpion venom's biological activities such as antimicrobial, antiviral, anti-cancerous and in immune diseases. Evolutionary perspective of peptides derived from different scorpion venoms are also described in this review. The most significant venom peptides are; Ctriporin, Chlorotoxins (cltx), Neopladine I and II, Meucin 24, Meucin 25 and Hp 1090. The most recognized scorpion species with pharmaceutical activities are; Pandinus imperator, Chaerilustricostatus, Buthus martensii, Mesobuthus eupeus, Leiurus quinnquestriatus, Tityus discrepans and Heterometrus bengalensis. CONCLUSION: The role of peptides in cardiovascular events and in treating osteoporosis signifies their importance. The role of peptides against pathogens, skin infections, pain-relieving effects, anti-malarial and anti-viral effects are discussed in detail. We further, summarized the classification of scorpion peptides among different toxins, their evolutionary process and the pattern of scorpion venom resource analysis.

Snake Venom as an Effective Tool Against Colorectal Cancer.

BACKGROUND: Cancer is considered one of the most predominant causes of morbidity and mortality all over the world and colorectal cancer is the most common fatal cancers, triggering the second cancer related death. Despite progress in understanding carcinogenesis and development in chemotherapeutics, there is an essential need to search for improved treatment. More than the half a century, cytotoxic and cytostatic agents have been examined as a potential treatment of cancer, among these agents; remarkable progresses have been reported by the use of the snake venom. Snake venoms are secreting materials of lethal snakes are store in venomous glands. Venoms are composite combinations of various protein, peptides, enzymes, toxins and non proteinaceous secretions. CONCLUSION: Snake venom possesses immense valuable mixtures of proteins and enzymes. Venoms have potential to combat with the cancerous cells and produce positive effect. Besides the toxicological effects of venoms, several proteins of snake venom e.g. disintegrins, phospholipases A2, metalloproteinases, and L-amino acid oxidases and peptides e.g. bradykinin potentiators, natriuretic, and analgesic peptides have shown potential as pharmaceutical agents, including areas of diagnosis and cancer treatment. In this review we have discussed recent remarkable research that has involved the dynamic snake venoms compounds, having anticancer bustle especially in case of colorectal cancer.