Characterization and resistant determinants linked to mobile elements of ESBL-producing and mcr-1-positive Escherichia coli recovered from the chicken origin.

The spread of antimicrobial resistance (AMR) in Escherichia coli is a complex process linked with various mobile genetic elements (MGEs) like plasmids, transposons, and integrons. This study aimed to determine the co-occurrence of ESBL and mcr-1 and their physical linkage with MGEs in E. coli. E. coli strains of chicken origin were obtained from different commercial farms of eastern China from 2010 to 2011. Antimicrobial sensitivity testing, identification of different antibiotic-resistant genes (ARGs), and prevalence and evidence involvement of integrons, ISEcp1, ISCR1, and ISApl1, were determined. A multiplex PCR was used to detect virulence genes and the phylogenetic clustering of isolates. Conjugation experiments, plasmid replicon typing were performed to know the transferability of ARGs and MGEs. A total of 83.33% of isolates were found to be multidrug-resistant (MDR). The incidence rate of blaCTX-M, blaSHV,blaTEM, and mcr-1 was found to be 30%, 10.95%, 8.09%, and 36.66%, respectively. The most prevalent combination was noticed for mcr-1 and blaCTX-M 73%, whereas the most prominent blaCTX-M alleles found, were blaCTX-M-55 46%, followed by blaCTX-M-14 31%, and blaCTX-M-15 13%. The frequency of ISEcp1, ISCR1, ISApl1, and int1 was 27.77%, 53.70%, 51.85%, and 70.37% respectively. Most ß-lactamases, especially blaCTX-M, blaSHV, and blaTEM, were associated with ISEcp1, ISCR1, and Integron 1, whereas the ISAPl1-mcr-1 segment was observed in mcr-1-positive E. coli isolates. Phylogrouping revealed that group A was the most predominant phylotype, whereas the common virulence genes detected in these isolates were EHEC, EAEC, and EPEC. Conjugation assay also indicated that multiple genetic elements were involved; common plasmids identified were FIB 61.11%, followed by IncHI2 48.14%, and FrepB 33.33%. Propagation of such MDR strains carrying multiple resistance elements among the bacterial population is a threat of worry.

A novel homozygous nonsense mutation in CCDC88A gene cause PEHO-like syndrome in consanguineous Saudi family.

Progressive encephalopathy, edema, hypsarrhythmia, and optic atrophy (PEHO) syndrome is an unusual Mendelian phenotype of unidentified origin that causes profound intellectual disability, optic nerve/cerebellar atrophy, epileptic seizures, developmental progress, pedal edema, and early death. Uncharacteristic affected individuals are often classified as having PEHO-like syndrome, although they may be misdiagnosed as having epileptic encephalopathy, a potential result of early birth. In this study, we report a consanguineous Saudi family with a novel homozygous nonsense mutation of the CCDC88A gene causing PEHO-like syndrome. The children were suffering from developmental delay, epilepsy, mental disability, optic nerve/cerebellar atrophy, and pedal edema. Whole exome sequencing was conducted for the members of the family who have the disorder to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation, identified a novel homozygous nonsense mutation c. 1292G > A, which was caused by p.Trp431* stop gain. This mutation was ruled out in 100 unrelated healthy controls. The nonsense homozygous mutation detected in this study has not yet been reported as pathogenic in the literature or various databases. In conclusion, a complete loss of protein function due to premature stop gain was caused by a mutation in exon 12 of CCDC88A. This loss may lead to PEHO phenotype. CCDC88A gene may therefore play an important and critical role for multiple aspects of normal human neurodevelopment.

Spatiotemporal analysis of dengue outbreaks in Samanabad town, Lahore metropolitan area, using geospatial techniques.

Dengue is endemic to Pakistan with its usual peak incidence in the post-monsoon period. In the last decade, dengue outbreaks have occurred in major urban areas particularly Karachi and Lahore, affecting large numbers of people. This study is an attempt to analyze the spatiotemporal variation of dengue fever (DF) in Samanabad town, Lahore metropolitan area. The study is based on secondary data, acquired from concerned government departments. Point level geo-coding is used to transform the relative location to the absolute location using Google Earth, and Global Position System (GPS) is used to validate the geo-coded location. Geographic information system (GIS) has been used to perform spatial analysis. It has been found that temporally DF prevalence varies from month to month and year to year. Major outbreak was observed in the year 2013 with more than 900 confirmed DF cases. Rainfall, temperature, and humidity have played a central role in outbreaks. The land cover pattern and population density further intensified the outbreak. Spatially, the number of DF incidence was high in those localities where the entire land is built-up and with little/no green space areas. Analysis reveals that DF is still a major threat to the area as socioeconomic and geographic conditions favor vector breeding and transfer of disease from one person/place to another. This study presents useful information regarding spatiotemporal patterns of dengue outbreak and may bring the attention of public health departments to formulate dengue-combating strategies. The methodology is general for spatiotemporal analysis and can be applied to other infectious diseases as well.

Spectral and Energy Efficient Low-Overhead Uplink and Downlink Channel Estimation for 5G Massive MIMO Systems.

Uplink and Downlink channel estimation in massive Multiple Input Multiple Output (MIMO) systems is an intricate issue because of the increasing channel matrix dimensions. The channel feedback overhead using traditional codebook schemes is very large, which consumes more bandwidth and decreases the overall system efficiency. The purpose of this paper is to decrease the channel estimation overhead by taking the advantage of sparse attributes and also to optimize the Energy Efficiency (EE) of the system. To cope with this issue, we propose a novel approach by using Compressed-Sensing (CS), Block Iterative-Support-Detection (Block-ISD), Angle-of-Departure (AoD) and Structured Compressive Sampling Matching Pursuit (S-CoSaMP) algorithms to reduce the channel estimation overhead and compare them with the traditional algorithms. The CS uses temporal-correlation of time-varying channels to produce Differential-Channel Impulse Response (DCIR) among two CIRs that are adjacent in time-slots. DCIR has greater sparsity than the conventional CIRs as it can be easily compressed. The Block-ISD uses spatial-correlation of the channels to obtain the block-sparsity which results in lower pilot-overhead. AoD quantizes the channels whose path-AoDs variation is slower than path-gains and such information is utilized for reducing the overhead. S-CoSaMP deploys structured-sparsity to obtain reliable Channel-State-Information (CSI). MATLAB simulation results show that the proposed CS based algorithms reduce the feedback and pilot-overhead by a significant percentage and also improve the system capacity as compared with the traditional algorithms. Moreover, the EE level increases with increasing Base Station (BS) density, UE density and lowering hardware impairments level.

Recent developments in therapeutic protein expression technologies in plants.

Infectious diseases and cancers are some of the commonest causes of deaths throughout the world. The previous two decades have witnessed a combined endeavor across various biological sciences to address this issue in novel ways. The advent of recombinant DNA technologies has provided the tools for producing recombinant proteins that can be used as therapeutic agents. A number of expression systems have been developed for the production of pharmaceutical products. Recently, advances have been made using plants as bioreactors to produce therapeutic proteins directed against infectious diseases and cancers. This review highlights the recent progress in therapeutic protein expression in plants (stable and transient), the factors affecting heterologous protein expression, vector systems and recent developments in existing technologies and steps towards the industrial production of plant-made vaccines, antibodies, and biopharmaceuticals.

Prevalence of rheumatoid arthritis in population with arthralgia presenting to a tertiary care hospital.

OBJECTIVE: To evaluate patients presenting to healthcare facilities because of joint pain and subsequently diagnosed with rheumatoid arthritis. METHODS: The prospective study was conducted from August 1, 2013,to January 20, 2014, at Jinnah Postgraduate Medical Centre, Karachi, and comprised patients presenting with joint pain. A questionnaire was used to collect data, and patients were diagnosed using American College of Rheumatology / European League Against Rheumatism Rheumatoid Arthritis Classification Criteria. Data was analyzed using SPSS 20. RESULTS: Of the 320 patients approached, 316(98.7%) filled the questionnaire. Eighty five (26.9%) were diagnosed as rheumatoid arthritis. Sixty (70.5%) were females and 25 (26.3%) were males. The frequency of rheumatoid arthritis was higher in people in 4th, 5th and 6th decades of life. Twenty five (7.9%) patients had positive family history, 77 (90.2%) were chronic sufferers and only 53 (16%) agreed to follow recommended immunosuppressive therapies. 212 (67.1%) patients belonged to highly literate class. CONCLUSIONS: Proper guidance regarding the disease was found to be lacking in the urban centre.

Human mutations in NDE1 cause extreme microcephaly with lissencephaly [corrected].

Genes disrupted in human microcephaly (meaning "small brain") define key regulators of neural progenitor proliferation and cell-fate specification. In comparison, genes mutated in human lissencephaly (lissos means smooth and cephalos means brain) highlight critical regulators of neuronal migration. Here, we report two families with extreme microcephaly and grossly simplified cortical gyral structure, a condition referred to as microlissencephaly, and show that they carry homozygous frameshift mutations in NDE1, which encodes a multidomain protein that localizes to the centrosome and mitotic spindle poles. Both human mutations in NDE1 truncate the C-terminal NDE1domains, which are essential for interactions with cytoplasmic dynein and thus for regulation of cytoskeletal dynamics in mitosis and for cell-cycle-dependent phosphorylation of NDE1 by Cdk1. We show that the patient NDE1 proteins are unstable, cannot bind cytoplasmic dynein, and do not localize properly to the centrosome. Additionally, we show that CDK1 phosphorylation at T246, which is within the C-terminal region disrupted by the mutations, is required for cell-cycle progression from the G2 to the M phase. The role of NDE1 in cell-cycle progression probably contributes to the profound neuronal proliferation defects evident in Nde1-null mice and patients with NDE1 mutations, demonstrating the essential role of NDE1 in human cerebral cortical neurogenesis.

Advancing the initiatives of sustainable coastal and marine areas development in Pakistan through marine spatial planning.

Coastal states are currently transitioning their traditional socio-economic activities into a single platform to address the emerging issues of the coast and marine environment. For countries like Pakistan, managing multiple coastal and marine activities is a significant challenge. The lack of proper management policies and an inefficient decision-making process put various types of pressure on the ecological functions of Pakistan's coastal and marine areas. The Government of Pakistan has not yet prioritized coastal and marine affairs in its policy agenda, resulting in a halt to the process of sustainable development. Moreover, a lack of financial allocation for large-scale coastal and marine projects, a shortage of trained human resources, insufficient coordination among organizations, and unstable political decisions and governance impede the sustainable delivery of the projects. This paper discusses Pakistan's coastal and marine policy targets and highlights various issues through PESTLE analysis, which encompasses political (P), economic (E), social (S), technological (T), legal (L), and environmental (E) factors that limit the advancement of sustainable coastal and marine development. This paper aims to determine the advantages of adopting marine spatial planning (MSP) in Pakistan and how its implementation can bring social, ecological, and economic prosperity. The study provides a baseline for the country's coastal and marine policymakers regarding the advancement of a blue economy through MSP.

A pair of carbazate derivatives as novel Schiff base ligands: DFT and POM theory supported spectroscopic and biological evaluation.

Schiff bases are mentioned as strongly important molecular scaffolds of industrial and medicinal purposes. Due to wide range applications of carbazate derivatives herein synthesis and characterization of a new Schiff base ligand, (E)-ethyl 2-(4-methoxybenzylidene)hydrazinecarboxylate and 4-(nitrobenzaldehyde)ethylcarbazate are reported. The compound was characterized on the basis of experimental and density functional theory calculations (using the B3LYP and 6-31 G(d,p)formalism combination). Among characterization techniques elemental analysis, FT-IR, UV-Vis and NMR spectroscopic evaluations were mainly employed to carry out the formulation of the compound. In addition to computational validation of characterization other significant molecular parameters were also evaluated including geometry optimization, frontier molecular orbital analysis (FMO) and Columbic interaction of different constituent atoms of the title compound. A good agreement has been found between DFT and experimental outcomes confined to prove the structure of the compound. Moreover, molecular docking and antimicrobial studies have proven the Schiff base as an effective bioactive compound.Communicated by Ramaswamy H. Sarma.

Design, Synthesis, Molecular Docking, and In Vitro Antibacterial Evaluation of Benzotriazole-Based ß-Amino Alcohols and Their Corresponding 1,3-Oxazolidines.

In the present study, a series of benzotriazole-based ß-amino alcohols were efficiently synthesized in excellent yields via aminolysis of benzotriazolated epoxides under catalyst- and solvent-free conditions. Further these ß-amino alcohols were successfully utilized to synthesize the corresponding benzotriazole-based oxazolidine heterocyclic derivatives. All the synthesized compounds were characterized by various spectroscopic techniques such as 1H NMR, 13C NMR, and mass spectroscopy for structure elucidation. The compounds were subjected to a microtiter plate-based antimicrobial assay. The antimicrobial activity results reveal that the compounds 4a, 4e, and 5f were found to be active against Staphylococcus aureus (ATCC-25923) with minimum inhibitory concentrations (MICs) of 32, 8, and 64 µM, respectively. Also, the compounds 4a, 4e, 4k, 4i, 4m, 4n, 4o, 5d, 5e, 5f, 5g, and 5h showed effective activity against Bacillus subtilis (ATCC 6633) with MICs of 64, 16, 16, 16, 64, 16, 64, 64, 32, 64, 8, and 16 µM, respectively. A biological investigation was conducted, including molecular docking of two compounds with several receptors to identify and confirm the best ligand-protein interactions. Hence, this study found a significant strategy to diversify the chemical molecules. The synthesized compounds play a potential role as an antibacterial intensifier against some pathogenic bacteria for the development of antibacterial substances.

The effect of hydro alcoholic extract of Juglans regia leaves in streptozotocin-nicotinamide induced diabetic rats.

Phytotherapy has been achieved to maintain glycemic control in patients with diabetes mellitus. The present study was conducted to evaluate the antihyperglycemic properties of the Juglans regia leaf extract in streptozotocin-nicotinamide induced diabetic rats. Nicotinamide was injected intraperitonealy (i.p.) 15 min before the injection of Streptozotocin (i.p.). One week after induction of diabetes, oral treatment started with extract of Juglans regia and Metformin and continued for 4 weeks. Fasting blood sugar, body weight, serum lipids and insulin level were measured in different groups. A significant reduction of glucose, HbA1c, total cholesterol and serum triglycerides were detected after 4 weeks in rats treated with Juglans regia leaves compared to the control groups. Thus, Juglans regia extract treatment showed potential hypoglycemic and hypolipidemic effects in type 2 diabetic rats.

Nitric oxide boosters as defensive agents against COVID-19 infection: an opinion.

In the prevailing covid times, scientific community is busy in developing vaccine against COVID-19. Under such fascination this article describes the possible role of nitric oxide (NO) releasers in aiding the immune system of a human body against this dreadful pandemic disease. Despite some prodrug antiviral compounds are in practice to recover the patients suffering from covid-19, however, co-morbidity deaths are highest among the total deaths happened so far. This concurrence of a number of diseases in a patient along with this viral infection is indicative of the poor immunity. Literature background supports the use of NO as immunity boosting agent and hence, the nitric oxide releasing compounds could act as lucrative in this context. Some dietary suggestions of NO-containing food items have also been introduced in this article. Also, the profound effect of NO in relieving symptomatic severity of covid-19 has been opined in this work.Communicated by Ramaswamy H. Sarma.

Antibiotic Antibiogram in Patients With Complicated Urinary Tract Infections in Nephrology Unit of South Waziristan.

Objectives To evaluate the antibiotic antibiogram in patients with complicated urinary tract infections (cUTIs) presenting to a Nephrology unit of South Waziristan. Methods A cross-sectional study was conducted at the Department of Nephrology, Sholam, South Waziristan. The study included all patients who presented with cUTIs and the symptoms included urinary urgency, hematuria, dysuria, suprapubic discomfort, and increased frequency. Those patients with clinical manifestations but are on antibiotics within the past five days were excluded. Results A total of 158 patients were included in the study with 113 (71.5%) females and 45 (28.5%) males. A total of 95 (60%) cases had gram-negative microbes, 47 (30%) had gram-positive cocci, and 16 (10%) had candida infection. In our study, the highly prevalent uropathogenic gram-positive bacteria showed the highest sensitivity to Linezolid, Rifampicin, and Vancomycin. Methicillin-resistant staph aureus was detected in 25% of isolates. All isolates of candida were sensitive to fluconazole. Gram-negative bacteria were highly resistant to ceftazidime, cefepime, ceftriaxone, and ciprofloxacin. Conclusion The development of bacterial resistance against multiple antibiotics is a global crisis that restricts the drug of choice for the treatment of cUTIs. In our study, we showed that overall, E.coli (gram negative) and S. Aureus (gram-positive) showed variable resistance to many antibiotics including ceftazidime, cefepime, piperacillin-tazobactam, ceftriaxone, and clindamycin.

Unilateral absence of external oblique musculo-aponeurotic complex during routine inguinal hernia repair.

INTRODUCTION: The isolated absence of the external oblique musculo-aponeurotic complex in adults is an extremely rare anomaly. This complex is an important contributor to the strength of the inguinal canal. The present case report describes the unilateral absence of the external oblique muscle in a patient. CASE PRESENTATION: A 40-year-old male patient presented with a history of intermittent lower abdominal pain for 5 years which had increased over the past 6 months. Abdominal examination revealed unilateral reducible, incomplete, left sided direct inguinal hernia. CLINICAL DISCUSSION: Elective unilateral Lichtenstein's mesh hernioplasty was planned for the patient. Intraoperatively, there was no evidence of the external oblique aponeurosis and the spermatic cord was noted deep to the thickened membranous fascial layer. The inguinal ligament was thin and atrophic and was attached to the pubic tubercle medially and anterior superior iliac spine laterally. There was no evidence of any superior aponeurotic connection to the inguinal ligament. A postoperative ultrasound examination of the abdomen confirmed the unilateral absence of the external oblique musculo-aponeurotic complex. CONCLUSION: The possibility of such an anomaly should be considered in patients without other risk factors for hernia.

Prevalence of Proteinuria and Hematuria in a Rural Population in the Southwest of Iran.

Acute and chronic kidney diseases are common and are associated with the risk of kidney failure. Early detection of these disorders prevents their progression to kidney damage in later stages. The aim of this study was to investigate the prevalence of proteinuria and hematuria in a rural population in Yasuj, Iran. In this cross-sectional study, 676 people (350 females and 326 males) participated. People with positive dipstick test results entered the second screening and the urinary protein-to-creatinine ratio (UPCR) was measured. People with UPCR ≥150 mg/g were evaluated for demographic and biochemical indicators. In the initial screening, 72 subjects (10.6%) tested positive by the dipstick test with trace proteinuria or higher. The UPCR results showed that this ratio was above 150 mg/g in 42 patients (6.2%), which was approximately equivalent to more than 150 mg of protein excreted per day. There was no significant relationship between the prevalence of proteinuria and the demographic and biochemical markers. Briefly, it seems that the prevalence of proteinuria found by the dipstick test was similar to that in other parts of the world. However, according to the UPCR index, the percentage of proteinuria was significantly higher than in other studies. Because of the unknown mechanism of proteinuria, more studies based on genetic tests and kidney biopsies are needed to determine the causes of proteinuria.

Flow injection spectrophotometric determination of methamidophos using online hydrolysis.

A new protocol for the online spectrophotometric determination of methamidophos has been developed. The method is based on online hydrolysis of methamidophos, and the resulting hydrolyzed product is reacted with sodium nitroproside to form a colored complex. The calibration curve is linear over the concentration range of 0.5-20 microgml(-1), with a molar absorptivity of 2.5x10(4) L mol(-1) cm(-1). The method is fast and reproducible with a sample throughput of 90 samples/h. The method is successfully applied to formulations and real samples.

Laparoscopic versus inguinal (Ivanissevich) varicocelectomy.

OBJECTIVE: To compare the postsurgical outcome of laparoscopic and open inguinal varicocelectomy. STUDY DESIGN: Quasi-experimental study. PLACE AND DURATION OF STUDY: Department of Surgery, Liaquat University of Medical and Health Sciences, Jamshoro, from July 2003 to June 2007. METHODOLOGY: One hundred seven patients underwent either open inguinal or laparoscopic varicocelectomy. Diagnosis was made by clinical examination and color Doppler scan in doubtful cases. Pre-operative semen analysis was done in all patients. Operative time, postoperative analgesic requirement in number of tablets, hospital stay in days, improvement in semen parameters in subfertile subjects, pain on visual analog score. and postoperative complications were recorded and compared between the two groups. RESULTS: There were 50 patients in each group, with age ranging from 12-50 years (26.9+/-7.67 in open inguinal and 26.2+/-7.08 in laparoscopic group). Average operative time was 34.8+/-7.89 minutes for open inguinal and 43.8+/-8.95 minutes for laparoscopic group. The analgesic requirement was 16.3+/-1.58 tablets in the open inguinal and 11.3+/-2.23 in the laparoscopic group. Postoperative pain was significantly less in the laparoscopic group. There was statistically significant (p < 0.001) improvement in sperm count as well as motility in both groups irrespective of procedure. CONCLUSION: The open inguinal (Ivanissevich) procedure and laparoscopic varicocelectomy had almost equivalent postoperative outcomes regarding improvement in semen parameters and postoperative complications. Open inguinal procedure had a shorter operating time while laparoscopic varicocelectomy had the advantage of less analgesic requirement and short hospital stay. On the whole, open inguinal (loupe magnified) varicocelectomy is an effective procedure where availability and costs of laparoscopic instruments are barriers.

An audit of informed consent in surgical patients at a university hospital.

BACKGROUND: To obtain informed consent is considered an integral part of modern clinical practice. It works as a safeguard of patient's rights and minimizes the chances of legal action against the physician in case of any complication arising from the proposed therapy. Objective was to evaluate the practice of informed consent in patients undergoing surgery in a University hospital. METHODS: A survey was conducted at different surgical departments of a university hospital during December 2007 to March 2008. Participants were selected from patients over the age of 18 years who had undergone elective or emergency surgery. All interviews were based on structured questionnaire. The patients were asked if an informed consent was taken or not before the surgery. They were also inquired if they were given information about the diagnosis, the surgical procedure planned and risks associated with it. The patients were also asked if they were informed about the types of anaesthesia proposed. RESULTS: A total of 106 patients were randomly selected for this study. In 8.5% cases, no consent was taken. Only 38% of the surveyed patients acknowledged that they actually understood the information imparted to them. 66% patients were informed about the type of anaesthesia proposed but none was given any hint about complications of anaesthesia. 11% patients actually signed the consent forms themselves. CONCLUSION: The quality of existing informed consent process in a university hospital is less than ideal. There is a great need to educate the doctors and healthcare regarding the importance of patient's autonomy and their right to the information about their medical condition and the proposed surgical procedures to ensure their participation in the decision making regarding their treatment.