In-silico analysis of potential anticancer drug for NEK7 and PPP1CA proteins overexpressed in pancreatic ductal adenocarcinoma.

NIMA-related kinase 7 (NEK7) and phosphoprotein phosphatase-1 catalytic subunit alpha (PPP1CA) are the most common proteins overexpressed in pancreatic ductal adenocarcinoma, which is the most common type of pancreatic cancer. The goal of the current study was to identify a possible NEK7 and PPP1CA therapeutic inhibitor. For this investigation, 5000 compounds were retrieved from the IMPPAT library of phytochemicals, which were docked with our respective target proteins. Also, a reference compound, gemcitabine, which is a Food and Drug Administration (FDA) approved drug, was docked with the target proteins. The binding energy of the reference compound for both the targeted proteins was -6.5 kcal/mol. The common ligand with the lowest binding energy for both targets is boeravinone B (PubChem ID: 14018348) with -9.2 kcal/mol of NEK7 and -7.6 kcal/mol for PPP1CA. The compound was further investigated through density function theory (DFT) and molecular dynamic simulation analysis. The root mean square deviation (RMSD), root mean square fluctuation (RMSF), radius of gyration (Rg), and hydrogen bonding analysis indicated the stability of the boeravinone B with the target proteins (NEK7 and PPP1CA).Communicated by Ramaswamy H. Sarma.

Herpes Simplex Virus Encephalitis: An Unexpected Outcome in a Polytrauma Patient.

An 84-year male was brought in the emergency after a road traffic accident leading to polytrauma with deteriorating consciousness. Prolonged unexplained unconsciousness led to cerebrospinal fluid examination. The polymerase chain reaction (PCR) of cerebrospinal fluid (CSF) was found to be positive for HSV-1 DNA. The patient was started on intravenous acyclovir and the consciousness level of the patient improved gradually. In this case, encephalitis was not suspected initially, because of the multiple traumatic injuries that needed management. Moreover, no features suggestive of encephalitis were present at the time of presentation, except for the non-specific symptom of drowsiness at the time of the accident. The patient was also diabetic and had chronic kidney disease as predisposing factors. It was primarily encephalitis which led to impaired consciousness that resulted in the road traffic accident in a very unlikely situation, i.e., hit by an ambulance inside the hospital. The reasons to suspect herpes simplex virus encephalitis (HSE) in this case were unexplained worsening level of consciousness, CSF findings suggestive of viral encephalitis along with highly deranged alanine aminotransferase (ALT) levels. This case highlights the importance of keeping a high index of suspicion for viral encephalitis in patients with risk factors, even in such a scenario of polytrauma. Key Words: Herpes simplex virus, Polytrauma, Viral encephalitis, Polymerase chain reaction.

Frequency And Clinical Spectrum Of Multidrug Resistant Acinetobacter Baumannii As A Significant Nosocomial Pathogen In Intensive Care Unit Patients.

BACKGROUND: Acinetobacter baumannii has emerged as one of the leading causes of multidrug resistant nosocomial infections worldwide. It is able to survive in hospital environment and build up diverse resistance mechanisms making it difficult to treat with current antibiotics. Objective: It was to determine the frequency and patterns of Acinetobacter baumannii in intensive care units (ICU) settings. METHODS: A cross sectional study was carried out in the Department of Microbiology, Armed Forces Institute of Pathology, Rawalpindi, from 1st July 2017 to 30th June 2019. A total of 603 non-duplicate clinical specimens were received from intensive care units. Specimens yielding growth of multidrug resistant Acinetobacter baumannii, were evaluated as per standard protocol. The antimicrobial sensitivity testing was performed as per Clinical and Laboratory Standard Institute guidelines (2017-2018). RESULTS: Among Acinetobacter baumannii (310 isolates), 5% were multidrug resistant, 93% extensively drug resistant and 1% pan drug resistant. Percentage of carbapenem resistant strains was 92%. In drugs like tigecycline and polymyxin, resistance was noted as 73% and 1% respectively. High yield of this superbug was mainly obtained from respiratory specimens (43.5%), whereas 24% were detected from wound infections and 29% from other samples. . CONCLUSION: This study showed a rapidly increasing resistance in Acinetobacter baumannii. Therefore, polymyxin remains the only option in our intensive care units, but its usage as empirical therapy in our setting has led to the emergence of resistance to this drug. Implementing infection control practices, antimicrobial stewardship and restricted use of polymyxin can play a significant role in reducing health care burden.

Superficial Thrombophlebitis caused by Extensively Drug-resistant Salmonella Enterica Serovar Typhi.

Salmonella enterica serovar typhi causes one of the most common blood stream infections, the typhoid fever. However, it can cause pyogenic infections involving different sites as well. Extensively drug resistant (XDR) strains of Salmonella typhi are resistant to all first line anti-typhoidal drugs (chloramphenicol, ampicillin and trimethoprim-sulfamethoxazole) as well as ciprofloxacin and ceftriaxone. XDR-strains were first reported from Pakistan in 2016, and since then the strains have been spreading. These XDR Salmonella cases not only pose a therapeutic challenge but also predispose to complications as a result of prolonged illness and delayed treatment. Here, we report a case of superficial thrombophlebitis at intravenous cannula site in a 49-year male, who was being treated for XDR-typhoid fever. To the best of our knowledge, thrombophlebitis of a superficial vein is an unusual complication of Salmonella typhi, not previously reported in literature. Key Words: Bacteremia, Thrombophlebitis, Extensively drug-resistant, Typhoid fever, Salmonella typhi.

Evaluation of direct drug susceptibility testing of blood culture isolates comparing it with conventional disk diffusion testing.

OBJECTIVE: To evaluate a direct antibiotic susceptibility testing method for blood culture.. METHODS: The cross-sectional comparative study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from December 2016 to October 2017. Direct antimicrobial susceptibility testing was performed from positive blood culture bottles. Bacterial identification was done by using API 10S. Different antimicrobial panels were employed for Gram-negative rods (GNRs), gram-positive cocci (like suspected Staphylococci and Enterococci). Results were compared with conventional disk diffusion testing and very major, major and minor errors were calculated. Result agreement and kappa coefficient scores were generated for categorical agreement. SPSS 24 was used for data analysis. RESULTS: Of the 101 bacterial isolates, 82(81.2%) were Gram negative rods and 19(18.8%) were Grampositive cocci. Among 781 bacteria-antibiotic comparisons, the number of very major errors was 3(0.4%), major errors were 7(0.9%) and minor errors were 12(1.5%), while, 759(97.2%) comparisons yielded the same results. The kappa coefficient was 0.946, showing almost perfect agreement. Direct identification of Gram negative rods was successful in 53(64.6%) cases. CONCLUSIONS: Direct susceptibility testing of blood culture produced reliable results for majority of the antimicrobials.

Pattern of Blood Stream Infections and their antibiotic susceptibility profile in a Neonatal intensive care unit of a tertiary care hospital; a current perspective.

OBJECTIVE: To determine the pattern of blood stream infections and their antibiotic susceptibility profile with infectivity predictors in a neonatal setting. METHODS: The descriptive cross-sectional study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, from December 1, 2016,to April 30, 2018, and comprised blood culture samples received in Bactec/BactAlert paediatric bottles from neonates aged 0-30 days admitted in the neonatal intensive care unit. The samples were processed as per the standard guidelines. Antibiotic susceptibility was checked as per guidelines of the Clinical and Laboratory Institute. VITEK 2 system was used for rapid identification and minimum inhibitory concentrations of the drugs. SPSS 24 was used for data analysis. RESULTS: Out of 640 samples, 172(27%) were culture-positive. Among them, 98(57%) were gramnegative rods, 50(29%) gram-positive cocci and 24(14%) were fungi. Of the 172 pathogens identified, Klebsiella pneumoniae was 39(22.7%) followed by Candida species 24(14%) and methicillin-resistant Coagulase-negative staphylococci 20(11.6%). Of Klebsiella pneumoniae isolates, 26(58%) were extended spectrum -lactamase producers. Among Acinetobacterbaumanii, 11(58%) were extensively drug resistant and Carbapenem-resistant strains were 20(91%). Also, 4(8%) isolates of Enterococcus faecium were vancomycin-resistant. CONCLUSIONS: Majority of the isolates causing blood stream infections in neonatal intensive care unit were multi drug resistant, posing a therapeutic challenge for the neo natologists .

Chryseobacterium Indologenes as a Novel Cause of Bacteremia in a Neonate.

Chryseobacterium indologenes is a rare human pathogen. It is an emerging species, least frequently reported from pediatric age group and known to cause pneumonia, bacteremia, and meningitis. The inherent resistant of one of the species to commonly prescribed broad-spectrum antibiotics makes it formidable challenge in the hospital settings. We report the first case of C. indologenes bacteremia from Pakistan, diagnosed in a preterm newborn in an intensive care setting.

Current Trends of Antimicrobial Susceptibility of Typhoidal Salmonellae Isolated at Tertiary Care Hospital.

OBJECTIVE: To determine the current trend of antimicrobial susceptibility of typhoidal Salmonellae. STUDY DESIGN: Descriptive cross-sectional study. PLACE AND DURATION OF STUDY: The study was carried out in the Department of Microbiology, PNS Shifa Hospital, Karachi, from January 2014 to December 2015. METHODOLOGY: Blood culture samples received from the wards and outpatient departments were included. Isolates of Salmonella were dealt with standard microbiological procedures. The antimicrobial sensitivity against the typhoidal Salmonellaewas determined using Kirby-Bauer disc diffusion method as per the guidelines of Clinical and Laboratory Standards Institute (2013). RESULTS: Atotal of 460 typhoidal Salmonellaewere isolated; out of which 270 were Salmonella typhiand 190 were Salmonella paratyphiA. The percentage of MDR isolates of S. typhiwas 57% and that of S. paratyphiAwas 42%. None of the isolates were resistant to ceftriaxone, while sensitivity to ciprofloxacin (07% and 0% for S. typhiand S. paratyphiA, respectively) was very low. CONCLUSION: There is high percentage of MDR isolates of typhoidal Salmonellaein our region. The antimicrobial sensitivity of typhoidal Salmonellaeto conventional agent has not improved enough to recommend their empirical use. There is almost complete resistance to fluoroquinolones as well, leaving very limited available treatment options.

Frequency of amount and axis of astigmatism in subjects of Rawalpindi, Pakistan.

OBJECTIVE: To assess the frequency of amount and axis of astigmatism with respect to age and gender. METHODS: The prospective, observational study was carried out from September 2009 to January 2010 at Armed Forces Institute of Ophthalmology, Rawalpindi. Patients from 5-70 years of age were included from both genders with no previous history of eye abnormality, surgery or eye pathology. An auto refractor-keratometre was used for measurement. Descriptive statistics were used to analyse data on SPSS 15. RESULTS: Among the total 288 patients, with-the-rule astigmatism (n = 21; 55%) had greater frequency in the 26-35 years sub-group. In terms of gender, 88 (48%); against-the-rule in 81 (44%); and oblique astigmatism in 14 (7.6%). In females, with-the-rule astigmatism was found in 52 (50%); against-the-rule in 36 (34.2%); and oblique in 17 (16%). The frequency of astigmatism > or = 0.25 ranged from 0.8% (n = 1) to 74% (n = 28) across all age groups. The amount of astigmatism which was noted to be the most common and prominent in the sample was < 1D. CONCLUSION: The amount and axis of astigmatism varied within the age sub-groups and within the gender.