Natural Alternatives to Non-biodegradable Polymers in 3D Printing of Pharmaceuticals.

BACKGROUND: Due to potential toxicity, non-biodegradable polymers used in 3D (3-dimensional) printing of drugs could be dangerous for patient safety and the environment. OBJECTIVE: This review aims to investigate the toxicity of non-biodegradable polymers and investigate the use of natural materials as an alternative in 3D printing medicines. The study evaluates the dangers connected to 3D printing. METHODS: A review of the literature on various 3D printing processes, such as inkjet printing, fused filament manufacturing, and extrusion-related 3DP systems, was done for this study. Also, the use of cellulose derivatives and natural materials in 3D printing and their potential as active excipients was proposed. RESULTS: The review identified potential toxicity risks linked to non-biodegradable polymers used in drug 3D printing. As a potential fix for this issue, the use of natural materials with improved mechanical and thermal properties was explored. The use of cellulose derivatives as an alternative to non-biodegradable polymers in 3D printing pharmaceuticals was also investigated in the study. CONCLUSION: This study emphasises the significance of evaluating the risks connected to drug 3D printing and recommends using natural materials as an alternative to non-biodegradable polymers. More study is required to create secure and reliable 3D printing processes for pharmaceuticals.

Early recognition and management of maternal sepsis in Pakistan: a feasibility study of the implementation of FAST-M intervention.

OBJECTIVE: Maternal sepsis is the third leading cause of maternal mortality globally. WHO and collaborators developed a care bundle called FAST-M (Fluids, Antibiotics, Source identification and treatment, Transfer and Monitoring) for early identification and management of maternal sepsis in low-resource settings. This study aimed to determine feasibility of FAST-M intervention in a low-resource setting in Pakistan. The FAST-M intervention consists of maternal sepsis screening tools, treatment bundle and implementation programme. DESIGN AND SETTING: A feasibility study with before and after design was conducted in women with suspected maternal sepsis admitted at the Liaquat University of Medical and Health Sciences hospital Hyderabad. The study outcomes were compared between baseline and intervention phases. In the baseline phase (2 months), the existing sepsis care practices were recorded, followed by a training programme for healthcare providers on the application of FAST-M tools. These tools were implemented in the intervention phase (4 months) to assess any change in clinical practices compared with the baseline phase. RESULTS: During the FAST-M implementation, 439 women were included in the study. 242/439 were suspected maternal infection cases, and 138/242 were women with suspected maternal sepsis. The FAST-M bundle was implemented in women with suspected maternal sepsis. Following the FAST-M intervention, significant changes were observed. Improvements were seen in the monitoring of oxygen saturation measurements (25.5% vs 100%; difference: 74%; 95% CI: 68.4% to 80.5%; p<0.01), fetal heart rate assessment (58% vs 100%; difference: 42.0%; 95% CI: 33.7% to 50.3%; p≤0.01) and measurement of urine output (76.5% vs 100%; difference: 23.5%; 95% CI: 17.6% to 29.4%; p<0.01). Women with suspected maternal sepsis received all components of the treatment bundle within 1 hour of sepsis recognition (0% vs 70.5%; difference: 70.5%; 95% CI: 60.4% to 80.6%; p<0.01). CONCLUSION: Implementation of the FAST-M intervention was considered feasible and enhanced early identification and management of maternal sepsis at the study site. TRIAL REGISTRATION NUMBER: ISRCTN17105658.

Feto-maternal outcomes of pregnancies in women with SLE: Experience from a tertiary care center of Asia.

OBJECTIVE: We aim to quantify the risk of maternal and fetal complications in patients with SLE in order to identify the impact of SLE on pregnancy and of pregnancy on SLE. METHODS: This retrospective record review study was conducted in Aga khan university hospital, Karachi, from Jan 1998 to Dec 2019. All pregnant patients with SLE diagnosed and delivered during this time were included in the study. Categorical variables were analyzed by using chi-square test and fisher exact test. Whereas quantitative point estimate was estimated as mean and SD. We matched the data and computed crude odds ratio of pre-eclamptic patients with respect to age of conception, gravida, and body mass index in both case and control group. RESULTS: The SLE disease activity was monitored during pregnancy under SLEDAI-2K Scoring system. The patients with mild (25.6%) and moderate (25.6%) disease activity were prevalent and most antenatal patients (51.7%) had flare up in third trimester. Adverse maternal outcomes include pre-eclampsia (28.8%), eclampsia (3.2%), cesarean section (57.6%), and thrombocytopenia (9.6%), whereas perinatal outcomes includes intrauterine growth retardation (24%), preterm birth <34 weeks (19.2%) and <37 weeks (63.2%), APGAR Score < 7 at 1 min (5.6%), and neonatal death (5.6%) found to be statistically significant in between two groups There were more high-risk patients (42) with positive IgG (88%), IgM (83.3%), and lupus anticoagulant (33.3%) as compared to low-risk APS group. CONCLUSION: Planned pregnancy and less severe disease flares during pregnancy is associated with more favorable feto-maternal outcomes.

Knowledge, attitudes, and practices (KAP) towards COVID-19 pandemic among pregnant women in a tertiary hospital in Karachi, Pakistan.

BACKGROUND: The aim of this study was to evaluate the knowledge, attitude, and practices (KAP) of the pregnant population during the COVID-19 pandemic in a tertiary care hospital. METHODS: This cross-sectional study was conducted at Aga Khan University Hospital, Karachi, Pakistan. KAP towards COVID-19 was assessed using 21-item questionnaires. A score for each category was calculated and points were summed. The outcome variables of KAP were compared with demographic characteristics. Data were analyzed by using SPSS 19. RESULTS: A total of 377 patients participated in the study. The majority of the patients were multiparous (36.8%) in the age group of 30-40years (42.4%). More than 90% of patients were aware of COVID-19 symptoms and mode of transmission. They were aware of no cure for disease and optimum social distance. Although < 50% of patients truly answered the questions regarding the impact of COVID-19 on the risk of congenital malformation, vertical transmission, and the effect of infection on the mode of delivery. Regarding attitude and practices,> 90% of patients were anxious about fetal and personal safety, they are using a facemask, sanitizing their hands regularly, and avoiding social gatherings. Univariate and multivariable linear regression analysis showed statistically significant results among demographic variables (age, parity, family members, occupational status, and source of information). CONCLUSION: Pregnant patients demonstrated inadequate knowledge regarding the impact of COVID-19 on pregnancy. However positive attitude and practices on preventive measures were good. This highlights the need for health education for pregnant women for COVID-19 to improve knowledge on a constant basis.

Development of mucoadhesive adapalene gel for biotherapeutic delivery to vaginal tissue.

Purpose: Alternate formulation strategies need to be devised for improving the absorption and bioavailability of drug molecules administered through the intravaginal route. Enhancing the coating of vaginal mucosa can aid the achievement of this goal. The aim of the current study is to develop a mucoadhesive formulation having adequate adhesiveness, spreading, and viscosity profiles that can ensure good tissue absorption of adapalene upon intravaginal application. Method: A combination of mucoadhesive agents has been employed, including Carbopol-934, HPMC K-15M, and xanthan gum, in varying ratios to formulate five different gels. Furthermore, a cost-effective UV-spectroscopic analytical method was developed to quantify the amount of adapalene in tested samples, both of in vitro and in vivo origin. The analytical method was validated for different parameters, including specificity, linearity, range, accuracy, precision, and ruggedness. The modified USP-II apparatus was used for dissolution studies, while in vivo pharmacokinetic validation was performed in a murine model. Result: Of all the tested formulations, on the basis of the rheo-mechanical attributes, ACX3 performed better than the rest, including the commercially available intravaginal reference product. ACX3 had an average adhesion time of 12 min and a spread diameter of 37 mm. It showed 35 mm as average distance travelled by the diluted sample for leakage assessment. The analytical method developed for the adapalene muco-adhesive gel was within the range for all the validation parameters. For further evaluating the performance of the formulation, dissolution studies were conducted in simulated vaginal conditions which showed 94.83% of drug release within 5 minutes, while on completion of 30 min, it was measured to be 92.90%. Moreover, approximately 67% of the administered drug was recovered after 5 min of administration as evaluated through tissue recovery procedures in mice. Conclusion: The study aided in development of a formulation which can enhance the muco-adhesion of the drug molecule, resulting in an improved pharmacokinetic profile. Moreover, it established an efficient assay method which can be employed for in vitro and in vivo quantification of adapalene in simulated and physiological fluids.

Influence of Preoperative Anxiety Level on Postoperative Pain After Cardiac Surgery.

Background Preoperative anxiety is generally neglected in the evaluation of cardiac surgery patients due to various reasons including insufficient literature and lack of simple assessment tools. In addition to this, the association between anxiety and postoperative complications including pain has been scarcely studied. The present study was designed to assess preoperative anxiety levels in all patients coming for cardiac surgery and then evaluate the effect of different levels of anxiety on postoperative pain scores. Methods This prospective cohort study was conducted in a single university hospital from March 2018 to December 2019. One hundred consecutive cardiac surgery patients between the ages of 18-65 years were enrolled in this study. The level of preoperative anxiety (assessed by State Anxiety Inventory) and its effect on postoperative pain and morphine consumption was assessed. Results The average age of the patients was 58.24±10.03 years of which 68% were male and 32% were female. Preoperative mild anxiety was observed in 64% of patients and moderate to severe anxiety in 36% of patients. Post-operative mean pain score was significantly high in the moderate to severe anxiety group as compared to the mild anxiety group [Mean pain difference =1.64 (95%CI: 1.38-1.89) p=0.0005], [Mean pain difference =0.51 (95%CI: 0.29-0.73) p=0.0005] at 12 hours and 24 hours respectively. Intraoperative and postoperative morphine consumption was significantly high in patients with moderate to severe anxiety. Conclusions Patients with moderate to severe anxiety before cardiac surgery experienced higher pain scores at a post-operative period which is significantly different from the mild anxiety group. Intraoperative and postoperative analgesic requirements were also significantly increased.

Failure rate of labor epidural: An observational study among different levels of trainee anesthesiologists in a university hospital of a developing country.

CONTEXT: Frequent use of labor epidural has also led to a corresponding increase in failed epidural analgesia (FEA). AIMS: This study aims to identify the overall rate of FEA and evaluate its association with trainee anesthesiologist at different years/levels of anesthesia residency training. SETTINGS AND DESIGN: Prospective observational study was conducted for one year in the labor room suit of a university hospital. METHODS AND MATERIAL: After university ethics committee approval, full-term parturient receiving labor epidurals and consenting for the study were included. FEA was identified by the presence of one or more set criteria of failure including; pain of numeric rating scale of >4 at 45 minutes after epidural placement, accidental dural puncture, need to re-site the epidural, abandoning the procedure, and maternal dissatisfaction with labor pain relief. STATISTICAL ANALYSIS USED: A binary logistic regression was used to assess the association between failure rate of labor epidural and grades of anesthesiologists. Odds ratio (OR) and 95% confidence interval (CI) were reported. P value ≤0.05 was considered significant. RESULTS: Out of 500 women included, 76 (15.2%) had FEA, which was significantly high in 2nd and 3rd year residents compared to 5th year and above level anesthesiologists [OR = 2.08; 95% CI: 1.17 to 3.67; P = 0.012]. Failure rate was also high but insignificant in 4th year residents compared to senior level anesthesiologists [OR = 1.78; 95%CI: 0.89 to 3.53; P = 0.098]. CONCLUSIONS: The incidence of FEA is comparable to those quoted in literature from developed countries and shows association to experience and year of training of anesthesia residents.

Post operative sore throat: Comparison between Macintosh versus Video Laryngoscope in patients intubated by trainee anaesthetists - A Randomised Control Trial.

OBJECTIVES: Postoperative sore throat (POST) is a common complication related to endotracheal intubation. The aim of this study was to compare the incidence of POST in patients intubated by trainee anaesthetist using Video Laryngoscope™ (VDL) or Conventional Macintosh Laryngoscope (CL). METHODS: Total 110 patient scheduled for elective laparoscopic cholecystectomy were included from main operating room of Aga Khan University Hospital between June 2017-2018. The standardized perioperative protocol was used for general anaesthesia. Selected patients were randomly allocated into conventional laryngoscopy (CL) group or video laryngoscopy (VDL) group. The evaluation of sore throat was done at 1st, 12th and 24th hour postoperatively using a ten-point visual analogue scale. RESULTS: The demographic characteristics, including intubation time, related complications or any other maneuver required were similar between the groups. The incidence of POST at 1st hour was 47% patients in CL group and 38% in VDL group (p=0.335). At 12th hour, 34.5% patients in CL and 38% in VDL reported POST (p=0.692). Similarly at 24th hour, 25% patients in CL and 16% in VDL group reported POST (p=0.669). CONCLUSIONS: There was no significant difference in incidence of POST for patients intubated by trainee anaesthetists using either CL or VDL. Objective evidence of training and laryngoscope technique can impact of POST.

Frequency of Intraoperative Hypotension After the Induction of Anesthesia in Hypertensive Patients with Preoperative Angiotensin-converting Enzyme Inhibitors.

Introduction The renin-angiotensin-aldosterone system (RAAS) is an important target in the treatment of hypertension. Angiotensin-converting enzyme (ACE) inhibitors block the conversion of angiotensin I to angiotensin II. ACE inhibitors not only treat hypertension but also decrease morbidity and mortality in heart failure patients and in patients with acute myocardial infarction. The discontinuation of ACE inhibitors before the surgery is still controversial. To assess the current magnitude of the problem in our population, we aimed to conduct this study, which evaluated the frequency of intraoperative hypotension after the induction of anesthesia in controlled hypertensive patients with preoperative ACE inhibitors. Material and methods This descriptive case series study was conducted at a tertiary hospital in a developing country after approval from the Ethics Review Committee. A total of 115 adult patients, from 16 to 60 years of age, who have undergone elective surgery, have controlled hypertension on the desired drugs for at least six months, have no history of any cardiac event, and have taken the drug on the morning of the surgery, were included in the study after written consent. The demographic data of the patients were entered into the proforma. Preoperative systolic, diastolic, and mean arterial pressure were recorded by the researcher or an assignee in the preoperative holding area. The patients were followed in the recovery room by the team conducting the study until 10 minutes after the arrival of the patient in the recovery room. All statistical analyses were performed using Statistical Packages for the Social Sciences version 19 (SPSS Inc., Chicago, IL). p-value ≤0.05 was considered significant. Results Of the 115 patients, 56 (48.7%) patients were in the age group between 51 and 60 years of age; 38 patients were between the ages of 41 and 50 years and only 21 patients were 40 years or less. On gender, 68 patients were female and 47 were male. According to body mass index (BMI), the majority of the patients were in the overweight group, amounting to 53 (46%), and 86 (74.78%) patients were known diabetics. Overall, 77 (66.96%) of the patients developed intraoperative hypotension with 41 (35.65%) patients requiring the use of vasopressors in order to correct the hypotension. No statistically significant difference was found between demographic and clinical variables. Conclusion Intraoperative hypotension is more frequent in patients with controlled hypertension on ACE inhibitors although more studies need to be conducted on a larger population in order to determine a more definitive result.

Next-Generation Sequencing and the CRISPR-Cas Nexus: A Molecular Plant Virology Perspective.

In recent years, next-generation sequencing (NGS) and contemporary Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR-associated (Cas) technologies have revolutionized the life sciences and the field of plant virology. Both these technologies offer an unparalleled platform for sequencing and deciphering viral metagenomes promptly. Over the past two decades, NGS technologies have improved enormously and have impacted plant virology. NGS has enabled the detection of plant viruses that were previously undetectable by conventional approaches, such as quarantine and archeological plant samples, and has helped to track the evolutionary footprints of viral pathogens. The CRISPR-Cas-based genome editing (GE) and detection techniques have enabled the development of effective approaches to virus resistance. Different versions of CRISPR-Cas have been employed to successfully confer resistance against diverse plant viruses by directly targeting the virus genome or indirectly editing certain host susceptibility factors. Applications of CRISPR-Cas systems include targeted insertion and/or deletion, site-directed mutagenesis, induction/expression/repression of the gene(s), epigenome re-modeling, and SNPs detection. The CRISPR-Cas toolbox has been equipped with precision GE tools to engineer the target genome with and without double-stranded (ds) breaks or donor templates. This technique has also enabled the generation of transgene-free genetically engineered plants, DNA repair, base substitution, prime editing, detection of small molecules, and biosensing in plant virology. This review discusses the utilities, advantages, applications, bottlenecks of NGS, and CRISPR-Cas in plant virology.

Molecular and biological characterization of Chilli leaf curl virus and associated Tomato leaf curl betasatellite infecting tobacco in Oman.

BACKGROUND: In Oman tobacco (Nicotiana tabacum; family Solanaceae) is a minor crop, which is produced only for local consumption. In 2015, tobacco plants exhibiting severe downward leaf curling, leaf thickening, vein swelling, yellowing and stunting were identified in fields of tobacco in Suhar Al-Batina region, Oman. These symptoms are suggestive of begomovirus (genus Begomovirus, family Geminiviridae) infection. METHODS: Circular DNA molecules were amplified from total DNA extracted from tobacco plants by rolling circle amplification (RCA). Viral genomes were cloned from RCA products by restriction digestion and betasatellites were cloned by PCR amplification from RCA product, using universal primers. The sequences of full-length clones were obtained by Sanger sequencing and primer walking. Constructs for the infectivity of virus and betasatellite were produced and introduced into plants by Agrobacterium-mediated inoculation. RESULTS: The full-length sequences of 3 begomovirus and 3 betasatellite clones, isolated from 3 plants, were obtained. Analysis of the full-length sequences determined showed the virus to be a variant of Chilli leaf curl virus (ChiLCV) and the betasatellite to be a variant of Tomato leaf curl betasatellite (ToLCB). Both the virus and the betasatellite isolated from tobacco show the greatest levels of sequence identity to isolates of ChiLCV and ToLCB identified in other hosts in Oman. Additionally clones of ChiLCV and ToLCB were shown, by Agrobacterium-mediated inoculation, to be infectious to 3 Nicotiana species, including N. tabacum. In N. benthamiana the betasatellite was shown to change the upward leaf rolling symptoms to a severe downward leaf curl, as is typical for many monopartite begomoviruses with betasatellites. CONCLUSIONS: The leaf curl disease of tobacco in Oman was shown to be caused by ChiLCV and ToLCB. This is the first identification of ChiLCV with ToLCB infecting tobacco. The study shows that, despite the low diversity of begomoviruses and betasatellites in Oman, the extant viruses/betasatellites are able to fill the niches that present themselves.

Effect of Pharmacological Agents Administered for Attenuating the Extubation Response on the Quality of Extubation: A Systematic Review.

Background Several drugs have been tried to obtund the hemodynamic extubation response but all have variable side effects that may affect the quality of short-term recovery. Objective Our primary objective was to evaluate the effect of pharmacological agents, such as dexmedetomidine, local anesthetics, and so on, administered for attenuating the extubation response on the quality of extubation, as judged by the presence or absence of cough, sedation, and laryngospasm/bronchospasm in adult patients who had undergone general anesthesia. A secondary objective was to evaluate the effect of these drugs on other immediate post-extubation complications such as respiratory depression, desaturation, bradycardia, hypotension, and nausea and vomiting (PONV). Methods This is a systematic review of (randomized controlled trials) RCTs with meta-analysis. The Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index of Nursing and Allied Health Literature (CINAHL), and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for RCTs on the effect of pharmacological agents on both the hemodynamic extubation response as well as the quality of extubation. Results Fourteen out of 24 included studies were subjected to a meta-analysis. The risk of cough was less likely in the intervention group as compared to control groups (OR 0.26, 95% CI 0.15 to 0.46, p<0.00001, I2=35%). Sedation, hypotension (OR= 10.47; 95% CI: 1.86, 58.80, p=0.008, I2=0%), and bradycardia (OR= 6.57; 95% CI: 2.09, 20.64, p=0.001, I2=0%) were reported with dexmedetomidine. Only one study reported laryngospasm with dexmedetomidine and two studies with opioids. Conclusion Dexmedetomidine 0.4 to 0.5 ug/kg was associated with smooth extubation, minimal coughing, no laryngospasm/ bronchospasm, and with stable hemodynamics, without causing respiratory depression, PONV, and desaturation. However, in higher doses (more than 0.5 ug/kg), it caused bradycardia, hypotension, and sedation. Other pharmacological agents, such as local anesthetics, calcium channel blockers, and opioids, did not attenuate cough associated with extubation.

Role of diagnostic factors associated with antioxidative status and expression of matrix metalloproteinases (MMPs) in patients with cancer therapy induced ocular disorders.

BACKGROUND: Cancer patients when treated with different chemotherapeutic drugs often develop mild to severe sight threatening diseases during or after chemotherapy. The mechanism involved in the pathogenesis of ocular toxicities is poorly understood. Oxidative stress, inflammation and MMPs (angiogenic factor) are involved in the progression of chemotherapy related ocular disorders. MATERIALS AND METHODS: The concentration of oxidative stress markers such as MDA, NO and levels of different antioxidant molecules such as SOD, CAT, GSH, GPx, GPr, VIT A, VIT E and VIT C present in the serum of chemotherapy treated patients (n = 50) and in normal persons (n = 20) were estimated by the direct spectrophotometric method while the concentration of TNF-α and MMP-9 activity were determined using human TNF-α and MMP-9 ELISA kits. RESULTS: The concentration of SOD and CAT (0.356 ±â€¯0.05 µg/dl and 1.26 ±â€¯0.01 µmol/mol of protein) was significantly lower as compared to that (1.09 ±â€¯0.03 µg/dl and 3.99 ±â€¯0.04 µmol/mol of protein) in controls. The levels of GPx (0.06 ±â€¯0.01 mmol/dl) in the cancer patients were much lower than those in the controls (0.78 ±â€¯0.06 mmol/dl). Lower level of GSH (0.96 ±â€¯0.003 µg/dl) in serum of the diseased group was observed as compared to healthy group (7.26 ±â€¯1.40 µg/dl). The level of Vit A, Vit C and Vit E was lower in systemic circulation of cancer patients (109.99 ±â€¯6.35 µg/ml, 1.26 ±â€¯0.36 µg/ml and 1.29 ±â€¯0.191 µg/ml) as compared to control subjects (166.35 ±â€¯14.26 µg/ml, 3.25 ±â€¯0.099 µg/ml and 6.354 ±â€¯2.26 µg/ml) respectively. The concentration of nitric oxide was significantly higher in the cancer patients (45.26 ±â€¯6.35 ng/ml) than that in the normal subjects (16.35 ±â€¯3.26 ng/ml). The higher concentration of MDA (8.65 ±â€¯3.26 nmol/ml) was observed in the patients than normal ones (1.254 ±â€¯0.065 nmol/ml). The quantity of TNF-α was significantly higher in chemotherapy treated patients (32.68 ±â€¯4.33 pg/ml) as compared to the control group (20.979 ±â€¯1.98 pg/ml). Significantly higher concentration of MMP-9 (40.26 ±â€¯3.26 ng/ml) was observed in the cancer patients than the controls (7.256 ±â€¯1.95 ng/ml). CONCLUSION: Lower levels of antioxidant enzymes and non-enzymatic small molecules and higher levels of oxidative stress and inflammatory clinical parameters such as NO, MDA, TNF-α and MMP-9 may be involved in the pathogenesis of systemic chemotherapy related ocular complications such as cataract, glaucoma, blepharitis, retinitis pigmentosa, macular degeneration, pterygium and retinal degeneration.

Comparative study of extrapolative factors linked with oxidative injury and anti-inflammatory status in chronic kidney disease patients experiencing cardiovascular distress.

BACKGROUND: Chronic kidney disease (CKD) is a group of heterogeneous abnormalities affecting the function and structure of the kidney and mostly further proceeds to cardiovascular damage prior to end stage renal disease (ESRD). The oxidative insult and inflammatory mediators have some undefined role in CKD and cardiovascular complications. It is therefore, aimed at to pin point the predictive factors in the development of cardiovascular disorder in patients with chronic kidney disease. METHODS: Fifty patients of CKD experiencing cardiovascular distress and twenty normal individuals having same age and sex acted as control during these observations. Blood samples (Each 5 ml) were drawn and subjected to centrifugation for 10-15 minutes to separate the serum at 4000-5000rpm. The levels of MDA, GSH, SOD, CAT, VIT C, VIT E, IL-1, TNF-alpha, nitric oxide (NO) and advanced oxidation protein products (AOPPs) were estimated and analyzed. RESULTS: The nitric oxide levels in the CKD patients decreased significantly (13.26±1.25 ng/ml) compared to controls (42.15±5.26 ng/ml). The serum vitamin E and C levels in these patients recorded 2.15±0.25 µg/ml and 0.97±0.09 µg/ml respectively as against their assigned controls which read 6.35±1.22 µg/ml and 3.29±0.25 µg/ml. Furthermore, a significantly higher level of Malondialdehyde (MDA) as1.25±0.07 nmol/ml was observed in CKD patients viz-a-viz relevant control. However, the serum SOD, catalase (CAT) and GSH levels in the same patients registered a significant decline as evident from respective figures 0.07±0.002 µg/dl, 1.22±0.012 µmol/mol, and 3.25±1.05 µg/dl. The control for these was observed as0.99±0.06 µg/dl, 3.19±0.05 µmol/mol, and 8.64±0.03 µg/dL. On the other hand, the IL-1 levels in the CKD patients found quite higher (402.5±18.26 pg/ml). This clearly points to substantial increase in oxidative insult and reduced NO levels leading to the renal and cardiovascular damage. CONCLUSION: Observations support the fact that the decrease in anti-oxidative capacity accompanied by higher inflammatory mediators in CKD is indicative of oxidative stress, consequently leading to CKD progression, in all probability to cardiovascular insult. The outcome reiterates that strategies be designed afresh to contain CKD progression to cardiovascular complications and ESRD. One way could be to focus on early detection of stress related to the disease. It requires analyzing the factors related to stress, such as the one reported here. Linking these factors with the symptoms could be a crucial step forward. And further, the disease could be monitored in a more disciplined manner.

Knock down of Whitefly Gut Gene Expression and Mortality by Orally Delivered Gut Gene-Specific dsRNAs.

Control of the whitefly Bemisia tabaci (Genn.) agricultural pest and plant virus vector relies on the use of chemical insecticides. RNA-interference (RNAi) is a homology-dependent innate immune response in eukaryotes, including insects, which results in degradation of the corresponding transcript following its recognition by a double-stranded RNA (dsRNA) that shares 100% sequence homology. In this study, six whitefly 'gut' genes were selected from an in silico-annotated transcriptome library constructed from the whitefly alimentary canal or 'gut' of the B biotype of B. tabaci, and tested for knock down efficacy, post-ingestion of dsRNAs that share 100% sequence homology to each respective gene target. Candidate genes were: Acetylcholine receptor subunit α, Alpha glucosidase 1, Aquaporin 1, Heat shock protein 70, Trehalase1, and Trehalose transporter1. The efficacy of RNAi knock down was further tested in a gene-specific functional bioassay, and mortality was recorded in 24 hr intervals, six days, post-treatment. Based on qPCR analysis, all six genes tested showed significantly reduced gene expression. Moderate-to-high whitefly mortality was associated with the down-regulation of osmoregulation, sugar metabolism and sugar transport-associated genes, demonstrating that whitefly survivability was linked with RNAi results. Silenced Acetylcholine receptor subunit α and Heat shock protein 70 genes showed an initial low whitefly mortality, however, following insecticide or high temperature treatments, respectively, significantly increased knockdown efficacy and death was observed, indicating enhanced post-knockdown sensitivity perhaps related to systemic silencing. The oral delivery of gut-specific dsRNAs, when combined with qPCR analysis of gene expression and a corresponding gene-specific bioassay that relates knockdown and mortality, offers a viable approach for functional genomics analysis and the discovery of prospective dsRNA biopesticide targets. The approach can be applied to functional genomics analyses to facilitate, species-specific dsRNA-mediated control of other non-model hemipterans.

RNAi-mediated mortality of the whitefly through transgenic expression of double-stranded RNA homologous to acetylcholinesterase and ecdysone receptor in tobacco plants.

The whitefly Bemisia tabaci (Genn.) is a pest and vector of plant viruses to crop and ornamental plants worldwide. Using RNA interference (RNAi) to down regulate whitefly genes by expressing their homologous double stranded RNAs in plants has great potential for management of whiteflies to reduce plant virus disease spread. Using a Tobacco rattle virus-derived plasmid for in planta transient expression of double stranded RNA (dsRNA) homologous to the acetylcholinesterase (AChE) and ecdysone receptor (EcR) genes of B. tabaci, resulted in significant adult whitefly mortality. Nicotiana tabacum L. plants expressing dsRNA homologous to B. tabaci AChE and EcR were constructed by fusing sequences derived from both genes. Mortality of adult whiteflies exposed to dsRNA by feeding on N. tabacum plants, compared to non-dsRNA expressing plants, recorded at 24-hr intervals post-ingestion for three days, was >90% and 10%, respectively. Analysis of gene expression by real time quantitative PCR indicated that whitefly mortality was attributable to the down-regulation of both target genes by RNAi. Results indicated that knock down of whitefly genes involved in neuronal transmission and transcriptional activation of developmental genes, has potential as a bio-pesticide to reduce whitefly population size and thereby decrease virus spread.

Obstetric patients in intensive care unit: Perspective from a teaching hospital in Pakistan.

OBJECTIVE: Review of obstetric cases admitted to the intensive care unit. DESIGN: Ten year retrospective review of individual patients' medical records. PARTICIPANTS: Records of obstetric patients admitted from 2005-2014. SETTING: Aga Khan University Hospital Karachi. MAIN OUTCOME MEASURES: Diagnosis at the time of admission, associated risk factors, and intervention required aspects of management and rate of mortality. FINDINGS: A total of 194 obstetric patients were admitted out of which 86.2% of patients had ventilator support. Mortality was not seen to be significantly associated with parity and antenatal/postnatal status. The median age of patients was 34 years, minimum length of stay was 24 hours and maximum stay was 53 days. Sixty one percent of patients were admitted to with organ system failure. The overall mortality rate was 21.64% (42/194). The mortality rate was five times more likely in patients who had gastro-intestinal complication {Odds Ratio=4.87; 95%CI: 1.65-14.36}. The largest group of patients {28.4%} presented with hematological diagnosis. CONCLUSION: When the intensive care unit admission became essential, primary diagnosis included: postpartum hemorrhage, hypertensive disorders, sepsis and infectious diseases. An increased vigilance of high-risk pregnant women and a stabilization of their condition before intervention is administered, improves the outcome of these women.

RNA Interference based Approach to Down Regulate Osmoregulators of Whitefly (Bemisia tabaci): Potential Technology for the Control of Whitefly.

Over the past decade RNA interference (RNAi) technology has emerged as a successful tool not only for functional genomics, but in planta expression of short interfering RNAs (siRNAs) that could offer great potential for insect pest management. The diet of insects feeding exclusively on phloem sieves contains water and sugars as main components, and the uptake of the liquid food greatly depends on the osmotic pressure within the insect body. Based on this physiological mechanism, transgenic plants of Nicotiana tabacum were generated expressing double stranded RNA (dsRNA) against both aquaporin (AQP) and a sucrase gene, alpha glucosidase (AGLU). These two genes are involved in osmotic pressure maintenance particularly in sap sucking insects, and the aim was to disrupt osmoregulation within the insect ultimately leading to mortality. Real time quantitative PCR (RT-qPCR) was performed to assess the suppression of gene expression in Bemisia tabaci (B. tabaci) and mortality was recorded during transgenic tobacco feeding bioassays. Feeding of insects on plants expressing dsRNA significantly reduced the transcript level of the target genes in B. tabaci after six days of feeding and more than 70% mortality was observed in B. tabaci fed on transgenic plants compared to the control plants. Our data shows that down-regulation of genes related to osmoregulation may find practical applications for the control of this important pest in cotton and other crops.

Non-coding RNAs in cancer diagnosis and therapy.

Cancer invasion involves a series of fundamental heterogeneous steps, with each step being distinct in its type regarding its dependence on various oncogenic pathways. Over the past few years, researchers have been focusing on targeted therapies to treat malignancies relying not only on a single oncogenic pathway, but on multiple pathways. Scientists have recently identified potential targets in the human genome considered earlier as non-functional but the discovery of their potential role in gene regulation has put new insights to cancer diagnosis, prognosis and therapeutics. Non coding RNAs (ncRNAs) have been identified as the key gene expression regulators. Long non-coding RNA (lncRNAs) reveal diverse gene expression profiles in benign and metastatic tumours. Improved clinical research may lead to better knowledge of their biogenesis and mechanism and eventually be used as diagnostic biomarkers and therapeutic agents. Small non coding RNAs or micro RNA (miRNA) are capable of reprogramming multiple oncogenic cascades and, thus, can be used as target agents. This review is aimed to give a perspective of non coding transcription in cancer metastasis with an eye on rising clinical relevance of non coding RNAs and their mechanism of action focusing on potential therapeutics for cancer pathogenesis.

Prehospital Airway Management in Emergency and Trauma Patients: A Cross-sectional Study of Ambulance Service Providers and Staff in a Low- and Middle-income Country.

BACKGROUND: Prehospital airway management (AM) is the first priority in the care of emergency and trauma victims as it has shown to improve survival in these patients. OBJECTIVE: The aim of this study was to assess training and knowledge of ambulance staff and availability of AM equipment in ambulances of Karachi, Pakistan. METHODS: This cross-sectional study was conducted from June through September 2014. Interviews were conducted with management of six ambulance service providers and 165 ambulance staff. Data from the management included availability of AM equipment in the ambulances, number and designation of staff sent for emergency calls, and AM training of staff. Ambulance staff were assessed for their awareness, knowledge, and training pertaining to AM. RESULTS: All the ambulance services (A through F) had basic equipment for AM but lacked qualified and trained staff. All services had solo drivers (98.3%) for emergency calls; however, Ambulance Service A also had doctors and paramedics. Only 35.7% (59/165) of ambulance staff had awareness regarding AM, out of which 77.9% (46/59) belonged to Ambulance Service A. Of these 59 staff, 81.4% received some form of AM training. Staff with AM awareness, when assessed for knowledge pertaining to AM steps and AM equipment, had a mean score of 4.7/5 and 8.4/12, respectively. CONCLUSION: Even though ambulances are equipped with basic equipment, due to lack of trained staff, these ambulances only serve the mere purpose of transportation. There is a need to train ambulance staff and increase ambulance to staff ratio to improve prehospital AM and patient survival.