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Nematode eggs are pervasive pathogens that infect billions of people and livestock every year. Adult parasitic nematode worms can be distinguished based on their size and morphology. However, their eggs, particularly their species Ascaris lumbricoides and Ascaris suum cannot be identified from each other. Identifying eggs of helminths from wastewater and sludge is important from a public health perspective to minimize the spread of Ascaris infections. Numerous methods exist for nematode identification, from a morphological-based approach to high throughput sequencing technology. However, these techniques are not consistent and often laborious and time-consuming. In this study, we demonstrate that non-invasive real-time identification of eggs is possible based on their intrinsic fluorescence. Using confocal microscopy, we investigate the autofluorescence properties of five species of nematode eggs and observe clear differences between genus and for the first time their species in sludge samples. This non-invasive imaging technique could lead to better understanding of these species and may assist in early control of diseases.

The objective of this study was based on the formulation development of fast dispersible Aceclofenac tablets (100 mg) and to evaluate the influence of pharmaceutical mixtures of directly compressible Avicel PH102 with Mannitol and Ac-di-sol on the compressional, mechanical characteristics and drug release properties. Fast dispersible Aceclofenac formulations were developed by central composite design (CCD). Among them the best possible formulation was selected on the basis of micromeritic properties, appropriate tablet weight and disintegration time for further study. Tablets were directly compressed using manual hydraulic press with a compressional force ranging from 7.2 to 77.2 MN/m2. Pre and post compression studies were performed and the compressed formulations (FA-FF) were assessed for different quality tests. The Heckel and Kawakita equations were applied for determination of compressional behavior of formulations. The quality attributes suggested that formulation (FB) containing avicel PH 102 (20%), mannitol (25%) and ac-di-sol (3%) as best optimized formulation showing better mechanical strength i.e. hardness 35.40 ± 6.93N, tensile strength 0.963 MN/m2, and friability 0.68%. Furthermore, compressional analysis of FB showed lowest PY value 59.520 MN/m2 and Pk value 1.040 MN/m2 indicating plasticity of the material. Formulation FB disintegrated rapidly within 21 seconds and released 99.92% drug after 45 min in phosphate buffer pH 6.8. Results of drug release kinetics showed that all formulations followed Weibull and First-order models in three different dissolution media. Avicel PH102 based formulation mixture exhibit excellent compactional strength with rapid disintegration and quick drug release., Competing Interests: The authors have declared that no competing interests exist.

To evaluate and compare the pharmacokinetic (PK) characteristics of a newly developed oral osmotically controlled drug delivery system of Eperisone 150 mg tablets with Eperisone immediate release (IR) marketed tablet brand as a reference formulation. It was a single dose, two treatment, two sequence, randomized, crossover study, involving 12 healthy human subjects. A modified, sensitive LC-ESI-MS/MS method was developed and validated as per FDA guidelines for estimation of Eperisone in plasma using a simple extraction and quick protein precipitation method. Non-compartmental pharmacokinetic model was used for PK analysis. Results were statistically compared using logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25. The bio-analytical method used for estimating drug plasma concentration was found to be simple, selective, linear, accurate and precise with 0.01 ng/ml as limit of detection. The comparative PK analysis revealed an insignificant difference in AUC 0-∞, AUC 0-t, V z /F, Cl/F and t 1/2λz , whereas a significant difference in C max , T max and MTTs were found. The relative bioavailability of Eperisone osmotic tablet was 109.7%. The osmotic controlled release drug formulation was found to release Eperisone for an extended period with less inter individual fluctuation in pharmacokinetic variables.

Propolis is a potent anti-microbial and natural anti-inflammatory by-product obtained from the beehive. Studies have demonstrated the superior biocompatibility and anti-microbial properties of propolis as compared to calcium hydroxide. However, its effect on postoperative endodontic pain is unknown. Therefore, this study aimed to investigate the impact of Chinese propolis paste as an intracanal medicament on postoperative endodontic pain intensities compared with calcium hydroxide (control) at different time intervals in necrotic teeth with periapical radiolucency. Eighty patients with single-rooted necrotic teeth with visible periapical radiolucency were recruited and randomly allocated to either the calcium hydroxide or propolis groups. After chemo-mechanical preparation and intracanal medicament insertion, patients were given the VAS (visual analogue scale) to record pain scores. Inter-group data were compared and analyzed using two-way repeated measure ANOVA (Bonferroni test). A p -value of < 0.025 was considered significant. In total, >78% of the patients experienced no or only mild post-operative pain in both the groups at all time intervals, without any significant difference in pain scores between the two groups ( p > 0.025). An overall flare-up rate of 14.8% was found. The results suggest that either of these medicaments can be used as an inter-appointment medication for the prevention of postoperative pain in necrotic cases.

Background: Wnt signaling is a cellular pathway involved in embryogenesis, development, and neoplasia. Wnt-pathway activation may accelerate prostate cancer androgen-independent growth and mediate antiandrogen resistance. Since 10-20% of advanced prostate cancers harbor Wnt-activating mutations, we aimed to characterize the clinical features and response to novel antiandrogens in such patients., Objective: To determine whether men with metastatic castration-resistant prostate cancer (mCRPC) who harbor Wnt-pathway mutations have poorer responses to first-line novel hormonal therapies: abiraterone/enzalutamide., Design, Setting, and Participants: Patients with mCRPC who received first-line abiraterone or enzalutamide were retrospectively evaluated. Using tumor DNA analyses, we queried for activating mutations in CTNNB1 or inactivating mutations in APC or RNF43, all of which are predicted to stimulate Wnt signaling. Presence or absence of at least one Wnt-activating alteration was correlated with clinical-pathologic characteristics and treatment outcomes., Outcome Measurements and Statistical Analysis: Time to prostate-specific antigen (PSA) progression, overall survival (OS), and PSA response were measured. Cox regression models were used to test associations between Wnt status and clinical-pathologic outcomes; Kaplan-Meier and log-rank analyses were used to compare time-to-event endpoints., Results and Limitations: Of 137 patients evaluated, 11% (n=15) had tumor DNA analysis showing at least one Wnt-stimulating alteration. Patients with Wnt-activating mutations had numerically fewer T3/T4 tumors than Wnt wild-type patients (31% vs 51%), but were otherwise generally balanced. Median time to PSA progression on first-line abiraterone/enzalutamide was shorter in Wnt-activated patients (6.5 vs 9.6mo, hazard ratio [HR] 2.34, p=0.003), as was OS (23.6 vs 27.7mo, HR 2.28, p=0.01). PSA responses were numerically worse in Wnt-activated patients (53% vs 75%, p=0.12). Presence of Wnt-activating alterations (adjusted HR [aHR] 2.33, p=0.007) and use of previous chemotherapy (aHR 1.83, p=0.004) were both independently associated with increased hazard of progression., Conclusions: Patients with somatic Wnt-pathway activating mutations have worse outcomes to first-line abiraterone/enzalutamide than Wnt wild-type patients. Our data suggest that additional genomically informed therapies are needed for this relevant subset of mCRPC patients., Patient Summary: In this report, we retrospectively examined outcomes of metastatic prostate cancer patients with or without Wnt-pathway mutations who received abiraterone or enzalutamide for the first time, in order to examine whether these mutations affect the prognosis. Our study suggested that patients who have Wnt-pathway activating mutations derived less benefit from abiraterone and enzalutamide when compared to patients without these mutations. We conclude that Wnt-pathway mutations might decrease the effectiveness of abiraterone and enzalutamide, and we propose that the Wnt pathway might be a good therapeutic target for these patients, in order to potentially reverse or prolong resistance to abiraterone and enzalutamide in men with Wnt mutations., (Copyright © 2019 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

The present research work elucidates the photocatalytic effect of titania on liquid crystal based sensor used to detect sodium arsenate in water. The titania nanoparticles with an average size of 18-20 nm were synthesized by hydrothermal method and calcined up to 500 °C to obtain pure anatase phase. The catalytic activity of titania nanoparticles was enhanced by surface modification with (3-aminopropyl) trimethoxysilane. The sensing experiment was performed under visible light irradiation while keeping the concentration of substrate, analyte, the thickness of the liquid crystal layer, temperature and pH values constant. In addition, span 80 (a non-ionic surfactant) was used to obtain homeotropic alignment of liquid crystals. The TiO₂ nanoparticles gave dark to bright texture within 53 min while the functionalized titania responded in less than 25 min under similar sensing condition. The detection results showed that the functionalized titania nanoparticles possess greater photocatalytic activity under visible light and enhanced the sensing response than unfunctionalized titania nanoparticles.

Background: Pathogenic mutations in genes mediating homologous recombination (HR) DNA repair are present in 20-30% of men with metastatic castrate-resistant prostate cancer (mCRPC). Radium-223 is a bone-seeking α-emitter that induces double-strand DNA breaks, thereby killing cancer cells in the bone microenvironment., Objective: To evaluate the potential impact of germline or somatic HR-deficiency (HRD) mutations on radium-223 efficacy in mCRPC with bone metastasis., Design, Setting, and Participants: This is a retrospective single-institution study. Medical records of 190 mCRPC patients for whom germline and/or somatic DNA sequencing data were available were reviewed. Of these patients, 28 had received standard-of-care radium-223 at Johns Hopkins between February 2013 and February 2018., Outcome Measurements and Statistical Analysis: Alkaline phosphatase (ALP) responses and time-to-ALP-progression were the coprimary endpoints. Prostate-specific antigen (PSA) responses, overall survival (OS), and time to next systemic therapy were also evaluated., Results and Limitations: Of the 28 patients included, 10 men (35.7%) had a germline/somatic HRD mutation (three in BRCA2, and one each in ATM, ATR, CHEK2, FANCG, FANCI, FANCL, and PALB2) and 18 (64.3%) did not. Men with HRD mutations (HRD+) had numerically lower ages (66 vs 73yr, p=0.25), more soft-tissue metastases (50% vs 38%, p=0.43), and higher baseline ALP levels (130 vs 108 U/l, p=0.84). Compared with HRD(-) men, HRD(+) patients showed greater ALP responses (80% vs 39%, p=0.04), longer time to ALP progression (median10.4 vs 5.8mo, hazard ratio [HR] 6.4, p=0.005), and a trend toward longer OS (median 36.9 vs 19.0mo, HR 3.3, p=0.11). PSA responses (0% vs 0%, p>0.99) and time to next systemic therapy (HR 1.5, p=0.39) were similar between the two groups. Results are limited by the retrospective nature of the analysis and the small sample size., Conclusions: In this exploratory study, bone-metastatic CRPC patients with inactivating HRD mutations demonstrated significantly improved ALP responses and time to ALP progression. These results should motivate prospective validation of the "synthetic lethality" hypothesis between HRD mutations and radium-223 activity., Patient Summary: In this report, we retrospectively examined outcomes to metastatic prostate cancer in patients with and without DNA repair mutations who received radium-223, a therapy that kills cancer cells by causing direct DNA damage. Our study suggested that patients who have inherited or acquired DNA repair gene mutations derived greater benefit from radium-223 when compared with patients without these mutations. We concluded that radium-223 might have an important role in this setting; however, prospective studies are needed to confirm whether DNA repair mutations truly make radium-223 work better or not., (Copyright © 2018 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Halloysite is a unique biocompatible aluminosilicate clay mineral with powder particles predominantly comprising of concentrically rolled nanotubular aggregates. Some recent studies have also contributed to its prospective case in oral drug delivery and dosage forms albeit with limited commercial viability. In this study, we have investigated the use of halloysite nanotubes (HNTs) as a directly compressible multifunctional tableting excipient using SeDeM diagram expert tool. SeDeM experimentations revealed that ~68% HNTs in the formulations were enough to be used as a directly compressible filler, binder, and disintegrant in diclofenac potassium formulations. In the next phase, a total of 8 formulations blends (IRF1-8) of diclofenac potassium (50 mg) with HNTs and Starch 1500® were prepared in different ratio using simple lattice mixture design and all were found satisfactory for direct compression. Compressed tablets (167 mg) had narrow weight variation (SD = ± 1.78 mg), good hardness (~9-9.5 kg), acceptable friability (<0.7%) and fast disintegration time (<1.5 min). Moreover, the cumulative dissolution at 1 h in phosphate buffer pH 6.8 was found compliant with the compendial criteria (> 92% against 75%). The dissolution profile was best fitted with Peppas-Sahlin model with Fickian diffusion as the only mechanism. f 2 similarity test revealed that almost all the tablets were pharmaceutical equivalent to the marketed formulation of the drug. A shelf-life of ~34 months was found upon long-term stability testing of the optimized formulation. This study demonstrates that this novel and economically viable clay material has a strong potential for commercial use in tableting of drug by direct compression., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Objective: In this study, pharmacokinetics (PKs) and bioavailability of newly developed extended release (ER) Itopride HCl 150 mg encapsulated ER pellets (test) and 150 mg Ganaton ER once-daily (OD) tablets (reference) were compared and evaluated under fasted and fed conditions., Methods: Twelve healthy human subjects were enrolled in a single dose, randomized; two treatments, two sequences, four period crossover study. A modified and validated liquid chromatographic method was used for the estimation of Itopride HCl in plasma samples. The data were analyzed through non-compartmental model using PK software Phoenix Winnonlin version 7. The outcome was measured on logarithmically transformed data, where p > 0.05 was considered as non-significant with 90% CI limit of 0.8-1.25., Results: The C max , AUC 0- t , and AUC 0-∞ values of Itopride HCl 150 mg ER pellets versus that of OD 150 mg tablets, in fed and fasted states, were within the limits specified by FDA to establish bioequivalence. The relative bioavailability of Itopride HCl 150 mg ER pellets were 1.019 (fed) and 1.081(fasted). The 90% CIs of AUC values for Itopride HCl 150 mg ER pellets and OD 150 mg tablets in fed versus fast were significantly greater and were not within 80-125% limit., Conclusion: The test and reference formulations had similar pharmacokinetic parameters in each condition studied. However, an increase in the amount of drug was observed in the fed state.

The objective of study was to develop Aceclofenac fast dispersible compacted pellets with improved taste and fast drug release. Pellets were prepared by extrusion spheronization technique followed by direct compression to make compacted pellets. Formulations were comprised of sucrose, mannitol, ac-di-sol, aspartame, pine apple flavor and magnesium stearate. A mixture of distilled water and isopropyl alcohol (1:1) was used for wet massing. The effect of ac-di-sol on the drug release pattern was examined and dissolution profile comparison was established. All formulations followed First order and Weibull models and f2 values indicated dissimilarity with the marketed immediate release product. Taste of compacted pellets was evaluated by a panel of 12 human volunteers. Formulation P5 was found to be an optimized formulation due to satisfactory quality attributes.

Famously posed by seventeenth-century French philosopher René Descartes, the mind-body problem remains unresolved in western philosophy and science, with both disciplines unable to move convincingly beyond the dualistic model. The persistence of dualism calls for a reframing of the problem through interdisciplinary modes of inquiry that include non-western points of view. One such perspective is Islamic theology of the soul, which, while approaching the problem from a distinct point of view, also adopts a position commensurate with (substance) dualism. Using this point of convergence as a conceptual starting point, we argue that bringing into dialogue contemporary neuroscientific, philosophy of mind, and Sunni Islamic theological discourses may provide a fruitful way of reframing the age-old mind-body problem. This paper provides an overview of how these three discourses have approached the issue of the mind-body (-soul) problem. Juxtaposing these three discourses, we hope, may ignite further scholarly dialogue and investigation.

Objective: The purpose of this study is to evaluate the accuracy of a noninvasive radiofrequency-based device, the Cardio-Pulmonary Stethoscope (CPS), to monitor heart and respiration rates, and detect changes in lung water content in human experiments and clinical trials., Methods: Three human populations (healthy subjects ( ), heart failure (), and hemodialysis () patients) were enrolled in this study. The study was conducted at the University of Hawaii and the Queen's Medical Center in Honolulu, HI, USA. Measurement of heart and respiration rates for all patients was compared with standard FDA - approved monitoring methods. For lung water measurements, CPS data were compared with simultaneous pulmonary capillary wedge pressure (PCWP) measurements for heart failure patients, and with change in weight of extracted fluid for hemodialysis patients., Results: Statistical correlation methods (Pearson, mixed, and intraclass) were used to compare the data and examine accuracy of CPS results. Results show that heart and respiration rates of all patients have excellent correlation factors, r≥0.9. Comparisons with fluid removed during hemodialysis treatment showed correlation factor of to 1, while PCWP measurements of heart failure patients had correlation factor of to 0.97., Conclusion: These results suggest that CPS technology accurately quantifies heart and respiration rates and measure fluid changes in the lungs., Significance: The CPS has the potential to accurately monitor lung fluid status noninvasively and continuously in a clinical and outpatient setting. Early and efficient management of lung fluid status is key in managing chronic conditions such heart failure, pulmonary hypertension, and acute respiration distress syndrome.

Background: Antiemetic agent Meclizine HCl, widely prescribed in vertigo, is available only in immediate release dosage forms. The approved therapeutic dose and shorter elimination half-life make Meclizine HCl a potential candidate to be formulated in extended release dosage form. This study was aimed to develop extended release Meclizine HCl pellets by extrusion spheronization using natural and synthetic lipids. Influence of lipid type, drug/lipid ratio and combinations of different lipids on drug release and sphericity of pellets were evaluated., Methods: Thirty two formulations were prepared with four different lipids, Glyceryl monostearate (Geleol ® ), Glyceryl palmitostearate (Precirol ® ), Glyceryl behenate (Compritol ® ) and Carnauba wax, utilized either alone or in combinations of drug/lipid ratio of 1:0.5-1:3. Dissolution studies were performed at variable pH and release kinetics were analyzed. Fourier transform infrared spectroscopy was conducted and no drug lipid interaction was found., Results: Sphericity indicated by shape factor (e R ) varied with type and concentration of lipids: Geleol ® (e R  = 0.891-0.997), Precirol ® (e R  = 0.611-0.743), Compritol ® (e R  = 0.665-0.729) and Carnauba wax (e R  = 0.499-0.551). Highly spherical pellets were obtained with Geleol ® (Aspect ratio = 1.005-1.052) whereas irregularly shaped pellets were formed using Carnauba wax (Aspect ratio = 1.153-1.309). Drug release was effectively controlled by three different combinations of lipids: (i) Geleol ® and Compritol ® , (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax. Scanning electron microscopy of Compritol ® pellets showed smooth surface with pores, whereas, irregular rough surface with hollow depressions was observed in Carnauba wax pellets. Energy dispersive spectroscopy indicated elemental composition of lipid matrix pellets. Kinetics of (i) Geleol ® and Compritol ® pellets, explained by Korsmeyer-Peppas (R 2  = 0.978-0.993) indicated non-Fickian diffusion (n = 0.519-0.597). Combinations of (ii) Geleol ® and Carnauba wax and (iii) Geleol ® , Compritol ® and Carnauba wax pellets followed Zero-order (R 2  = 0.991-0.995). Similarity test was performed using combination of Geleol ® and Compritol ® (i) as a reference., Conclusions: Matrices for the extended release of Meclizine HCl from extruded-spheronized pellets were successfully formed by using three lipids (Geleol ® , Compritol ® and Carnauba wax) in different combinations. The encapsulated pellets of Meclizine HCl can be effectively used for treatment of motion sickness, nausea and vertigo for extended period of time.

Aims: In flu pandemics, pharmacy students' knowledge, attitudes, and practices are critical to save patients life. The objective of study was to determine the knowledge of and attitude toward the pandemic influenza among the pharmacy students of Karachi, Pakistan., Settings and Designs: The cross-sectional study was conducted from September to December 2014 by adopting a prevalidated questionnaire distributed to senior pharmacy students (final year) in seven private and public sector universities of Karachi., Materials and Methods: A total of 443 pharmacy students responded the survey. Data regarding sociodemographic characteristics of the students, perceptions, level of knowledge and attitudes toward influenza, and prophylactic measures were collected., Statistical Analysis: To compute the correlation between different variables, data were analyzed using Pearson's Chi-square statistic method. P < 0.05 was considered statistical significance for all analysis., Results: Influenza was identified as a viral disease ( n = 423; 95.48%) and 282 (71.2%) students correctly identified it as disease affecting humans and pigs. Textbooks reported as most common source of knowledge ( n = 282; 64%). Most common symptoms identified were fever (81.94%), sore throat (64.1%), and nonproductive cough (43.34%). The most common preventive measures were covering nose and mouth (268; 60.5%) and wearing protective coverings (254; 57.3%). Only half of the students correctly reported about the route of administration (180; 40.6%) and strains in vaccine (186; 41.98%). The best time for administration of such vaccine was known by only 156 pharmacy students (35.34%). The majority of the students (82.6%) had no idea about the manifestation of influenza pandemic. Knowledge regarding influenza differed according to gender and institutions differing in their affiliation with tertiary care hospitals., Conclusion: It was observed that knowledge about disease progression, transmission, vaccination, and treatment in pharmacy students, especially those who are not getting clinical training in tertiary care hospitals was limited. There is an urgent need to develop awareness programs to increase knowledge of influenza among clinical pharmacists as they are more susceptible to infections and community as a whole., Competing Interests: There are no conflicts of interest.

In bulk phase, liquid crystalline molecules are organized due to non-covalent interactions and due to delicate nature of the present forces; this organization can easily be disrupted by any small external stimuli. This delicate nature of force balance in liquid crystals organization forms the basis of Liquid-crystals based sensing scheme which has been exploited by many researchers for the optical visualization and sensing of many biological interactions as well as detection of number of analytes. In this review, we present not only an overview of the state of the art in liquid crystals based sensing scheme but also highlight its limitations. The approaches described below revolve around possibilities and limitations of key components of such sensing platform including bottom substrates, alignments layers, nature and type of liquid crystals, sensing compartments, various interfaces etc. This review also highlights potential materials to not only improve performance of the sensing scheme but also to bridge the gap between science and technology of liquid crystals based sensing scheme., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Oxaliplatin, a third generation novel platinum compound is the most effective first line chemotherapeutic agent for colorectal cancer (CRC) in combination with 5FU and leucovorin. It is indicated for pancreatic, gastric and testicular cancers combined with bevacuzimab, capecitabine, irinotecan and other cytotoxic agents. However, moderate to severe hypersensitivity reactions (HSR) during or after oxaliplatin infusion usually require cessation of chemotherapy or substitution of the key therapeutic drug which largely interferes with improved patient prognosis. This mini- review showcases recent and accepted opinions/approaches in oxaliplatin induced HSR management. Physicians and oncologists have varying attitudes regarding the decision to rechallenge the patient after an HSR experience, efficacy of desensitization protocols, effectiveness and selection of drugs for premedication and possibilities of cross sensitivity to other platinum agents (e.g. carboplatin). A brief insight into underlying molecular mechanisms and clinical manifestations of oxaliplatin induced HSR is offered. We have also discussed the management of oxaliplatin induced HSR and risk stratification for a successful and complete chemotherapeutic plan.

Background: Owing toGiven the high costs of drugs to treat multi-drug resistant tuberculosis (MDR-TB), the Green Light Committee (GLC) initiative enables TB programs to procure quality-assured drugs at reduced prices. Despite price reductions, internationally quality assured (IQA) drugs can be more expensive than locally procured drugs. There is little evidence to inform decision-makers about whether IQA drugs are more effective than local drugs. This is the first study to compare outcomes between MDR-TB patients treated using IQA, and locally procured drugs in the same hospitals during the same time period., Methods/findings: A retrospective cohort study was conducted in three hospitals across Pakistan. Data on baseline characteristics and treatment outcomes during the first six months of treatment were extracted from hospital records of adult culture-positive pulmonary MDR-TB patients starting treatment between January 2011 and June 2012. Two cohorts were defined: patients receiving IQA drugs, and patients receiving locally procured non-IQA drugs. Data were analysed using Kaplan-Meier curves and Cox proportional hazards regression. The primary outcome compared between cohorts was time to culture conversion. Of 231 patients, 90 were in the IQA and 141 in the non-IQA cohorts. Baseline characteristics were similar except for higher frequency of quinolone resistance in the IQA cohort. Overall, 193 patients (84%) culture converted. Culture conversion was not faster in the IQA cohort; the median time was 81 and 68 days in the IQA and non-IQA cohorts, respectively. Unadjusted and adjusted hazard ratios for culture conversion in IQA verses non-IQA cohorts were 0.82 (95%-CI, 0.62-1.10) and 0.95 (95%-CI, 0.66-1.36) respectively., Conclusions: Use of good quality, locally procured drugs can be effective in treating MDR-TB, may involve lower costs than using IQA drugs and could strengthen developing country drug quality assurance systems. This may be a suitable alternative in lieu of or whilst awaiting arrival of internationally procured medicines.

Background: Research has been done to investigate the effect of intermittent complete fasting on human physiological parameters but the effect of fasting on blood pressure remains relatively unexplored. Research in animal models suggests a hypotensive effect with an undetermined mechanism. Muslims worldwide fast daily from dawn to dusk throughout the Islamic month of Ramadan. This study was to investigate the proposed hypotensive effect of Ramadan fasting in males over A period of 20 days and to study the relationship of the pattern of blood pressure variation with body mass index change., Methods: A repeated measures observational study design was implemented with convenient sampling. Study group included 40 normotensive, non-smoker males with no known comorbidities between the ages of 18-40 who fasted daily in the month of Ramadan. One set of BP readings, each, was taken one week before the start of Ramadan and on the 7th, 14th and 21st day of Ramadan which included pre and post Iftar measurements along with other variables. Data was analysed by repeated measures ANOVA using SPSS. The differences were compared with critical values generated by Tukey's Method., Results: There was a significant drop in systolic BP of 7.61 mmHg before Iftar, 2.72 mm-Hg after Iftar (p<0.005). There was a significant effect of Ramadan on diastolic BP (p<0.005), the drop being 3.19 mmHg. The drop in body mass index was significant only before Iftar at 0.3 kg/m2 (p<0.005). Pulse rate showed a significant drop of 7.79 bpm before Iftar and a significant rise of 3.96 bpm (p<0.005)., Conclusions: Intermittent fasting causes a drop in both systolic and diastolic blood pressure in normotensive males.

Objectives: Currently available vacuum devices used to assist women undergoing complicated labour are unsuitable for use in low-resource settings. The objective of this study was to evaluate the safety and feasibility of a new low-cost vacuum device, named Koohi Goth Vacuum Delivery System (KGVDS), designed for use in low-resource settings., Methods: A hospital-based, multicentre, prospective cohort study with no control group was conducted in Karachi, Pakistan. After training, KGVDS devices were made available for use by labour room staff at their discretion when instrumental delivery was indicated. Women to whom KGVDS was applied were followed from the start of labour until discharge. Feasibility was assessed in terms of successful expulsion of the foetal head following application of KGVDS and ease of use ratings. Safety was assessed by observing maternal and newborn post-delivery outcomes prior to discharge., Results: Koohi Goth Vacuum Delivery System was applied to 137 women requiring instrumental delivery, of whom 111 (81%; 95% CI = 74-88%) successfully expelled the foetal head assisted by KGVDS and 103 (75%) stated that they would agree to use KGVDS again. There were no serious maternal or neonatal injuries or infections related to KGVDS use. The mean score for 'ease of use' given by doctors and midwives using the device was 8 of 10., Conclusions: Koohi Goth Vacuum Delivery System was feasible and safe to use for assisting complicated deliveries in low-resource hospitals in this initial evaluation. Our results indicate that this new device may have the potential to improve birth outcomes in settings where most mortality occurs and that further evaluations should be conducted., (© 2014 John Wiley & Sons Ltd.)

Background: Uptake of family planning services in Pakistan has remained slow over the past decade despite a rapid increase in availability and awareness, indicating that social barriers may be preventing uptake. Social barriers such as opposition by family members have largely been studied qualitatively; there is a lack of quantitative evidence about the effect of different family members' opposition on women's intention to use contraceptives. The objective of this study was to quantitatively evaluate the effect of family members' opposition to family planning on intention to use contraception amongst poor women in Pakistan who have physical access to family planning services., Methods: An unmatched case control study (nested within a larger cohort study) was conducted in two public hospitals in Karachi, Pakistan. Univariable and multivariable logistic regression analyses were conducted to compare risk factors between women that were not intending to use any contraceptive methods in the future (cases) and women that were planning to use contraceptive methods (controls)., Results: 248 cases and 496 controls were included in the study. Negative contraceptive intent was associated with no knowledge of contraception (AOR = 3.79 [2.43-5.90]; p < 0.001), husband's opposition (AOR = 21.87 [13.21-36.21]; p < 0.001) and mother-in-law's opposition (AOR = 4.06 [1.77-9.30]; p < 0.001)., Conclusions: This study is the first to quantitatively assess the effect of opposition by different family members on women's contraceptive intent in Pakistan. Our results indicate that of all family members, husband's opposition has the strongest effect on women's intention to use contraception, even when the women have knowledge of and physical access to family planning services.

Background: To assess the frequency and severity of gastrointestinal adverse effects in advanced colorectal carcinoma patients treated with four different schedules of FOLFOX., Materials and Methods: Patients (median age 61 years) who underwent surgery were included in the study. All had measureable disease at CT scan, ultrasonography or clinical examination. Toxicity was graded on a scale of 1-5 according to the general grade definition of CTC v2.0. The severity of adverse effects (Grade 3 and 4) assessed in each treatment arm was compared., Results: Differences between the incidence rates of 3 and 4 toxicity and all grades of toxicity for all parameters in GI toxicity were very highly significant (p<0.001). Severe gastrointestinal symptoms of toxicity were noted with FOLFOX7 (oxaliplatin 130 mg/m2). Grade 3 diarrhea was reported in 25% patients and grade 4 diarrhea in 4% in the FOLFOX7 treatment arm. Grade 2 vomiting was very frequently reported in the FOLFOX4 treatment arm (oxaliplatin 85mg/m2). Grade 2 stomatitis was reported in 42% patients treated with mFOLFOX6 (oxaliplatin 100mg/m2). Differences in the incidence rate of nausea, diarrhea and stomatitis among all treatment arms of FOLFOX were significant (p<0.05) ., Conclusions: Severe diarrhea is associated with FOLFOX7 treatment. No grade 3 or 4 GI toxicity was reported in patients of the mFOLFOX6 arm.

Objective: A case-control study aiming to evaluate the relationship between Bsm I and Apa I restriction fragment gene polymorphisms and colorectal cancer (CRC) was carried out in Kashmir, including a total of 368 subjects (180 cases and 188 controls)., Methods: DNA samples extracted from the blood of the subjects were analyzed for 3' untranslated region (3' UTR) Apa I and Bsm I polymorphisms using restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR)., Results: A statistically significant 2.7-fold increased risk was observed in individuals found homozygous for the presence of the 'b' allele, in comparison to subjects homozygous for the 'B' allele (odds ratio (OR) 2.7, 95% confidence interval (CI) 1.49-4.86 (Bsm I)), and a statistically insignificant 2-fold increased risk was found among individuals with the 'aa' genotype, as compared to subjects with the 'AA' genotype (OR 2.017, 95% CI 0.86-4.7). Our study also yielded statistically significant results when the Apa I polymorphism was stratified by age (≤ 50 years) and dwelling area (rural area), and the Bsm I polymorphism by gender (male gender), suggesting a possible role of Apa I and Bsm I polymorphisms in the etiology of CRC in Kashmir., Conclusion: We conclude that Apa I and Bsm I single-nucleotide polymorphisms (SNPs) in the vitamin D receptor gene (VDR) might be associated with susceptibility to CRC among Kashmiris., (© 2014 S. Karger GmbH, Freiburg.)

The aim of this study was to develop a sustained release hydrophilic matrix tablet of Diltiazem HCl and evaluates the effect of formulation variables (e.g. lubricant, binder, polymer content and viscosity grades of HPMC) on drug release. Twelve different formulations (F1-F12) were prepared by direct compression. The results of the physical parameters and assay were found to be within the acceptable range. Rate of drug release was found to be slow as the fraction of the polymer was increased from 20-50%. The drug release rate from tablets containing K4M was effectively controlled by increasing the talc concentration, whereas the burst effect was reduced by increasing binder content. The drug release was higher with K4M as compare to K100M. Model-dependent and independent methods were used for data analysis and the best results were observed for K4M in Higuchi (R(2)=0.9903-0.9962) and K100M in Baker and Lonsdale (R(2)=0.9779-0.9941). The release mechanism of all formulations was non-Fickian. F7 (50% K4M, 2% talc, 10% Avicel PH101) and F11 (40% K100M) were very close to targeted release profile. F12 (50% K100M) exhibited highest degree of swelling and lowest erosion. The f1 and f2 test were performed taking F11 as a reference formulation.

The University of Michigan conference "Where Religion, Policy, and Bioethics Meet: An Interdisciplinary Conference on Islamic Bioethics and End-of-Life Care" in April 2011 addressed the issue of brain death as the prototype for a discourse that would reflect the emergence of Islamic bioethics as a formal field of study. In considering the issue of brain death, various Muslim legal experts have raised concerns over the lack of certainty in the scientific criteria as applied to the definition and diagnosis of brain death by the medical community. In contrast, the medical community at large has not required absolute certainty in its process, but has sought to eliminate doubt through cumulative diagnostic modalities and supportive scientific evidence. This has recently become a principal model, with increased interest in data analysis and evidence-based medicine with the intent to analyze and ultimately improve outcomes. Islamic law has also long employed a systematic methodology with the goal of eliminating doubt from rulings regarding the question of certainty. While ample criticism of the scientific criteria of brain death (Harvard criteria) by traditional legal sources now exists, an analysis of the legal process in assessing brain death, geared toward informing the clinician's perspective on the issue, is lacking. In this article, we explore the role of certainty in the diagnostic modalities used to establish diagnoses of brain death in current medical practice. We further examine the Islamic jurisprudential approach vis-à-vis the concept of certainty (yaqīn). Finally, we contrast the two at times divergent philosophies and consider what each perspective may contribute to the global discourse on brain death, understanding that the interdependence that exists between the theological, juridical, ethical, and medical/scientific fields necessitates an open discussion and active collaboration between all parties. We hope that this article serves to continue the discourse that was successfully begun by this initial interdisciplinary endeavor at the University of Michigan.

Esophageal cancer ranks 8th among the most frequently occurring cancers of the world. The exact cause of esophageal squamous cell carcinoma (ESCC) is unknown; however, some factors like smoking, alcohol intake, consumption of fungal-contaminated, spicy, or nitrosamine-containing foodstuffs and hot beverages, together with various genetic factors, have been found associated with the occurrence of this disease in various parts of the world. Much work has been carried out to elucidate the role of various gene mutations and polymorphisms in esophageal mucosal cancer. Previous studies have suggested that esophageal cancer-related gene 1 (ECRG1), as a novel candidate of the tumor suppressor gene family, is expressed in normal esophagus, liver, colon and lung tissues, but the expression is seen to be down-regulated in tumors, especially in ESCC, and in adjacent tissues. The Arg290Gln polymorphism in exon 8 of the ECRG1 gene has been studied in particular in a number of cases and has been observed to play an active role in the development of ESCC. This suggests that substitution of the arginine in the conserved catalytic domain of the ECRG1 protein might reduce its catalytic capacity by impacting its 3-dimensional conformation, thereby causing the genetic susceptibility to ESCC., (Copyright © 2013 S. Karger AG, Basel.)

Roles of the vitamin D receptor in etiology of cancers, including colorectal cancer, have been repeatedly stressed in different parts of the world. A case control study aimed to evaluate the relationship between the two was therefore initiated in Kashmir, known both for its increasing incidence of gastrointestinal cancers and deficiency of micro-nutrients especially vitamin D. The study included a total of 617 subjects (312 colorectal cancer cases and 305 controls), with sampling carried out over a period of 5 years. DNA samples from the blood of the subjects were analyzed for start codon Fok I VDR polymorphism. We obtained a 1.3 fold increased risk among individuals homozygous for f variants as compared to subjects homozygous for F allele (odds ratio OR 1.3, 95%CI, 0.861-1.65). Our study also showed statistically significant results when dwelling and tumor location characteristics were stratified with Fok I polymorphism, all of which suggests a possible role of Fok I polymorphism in the etiology of CRC in Kashmir.

Background: In many countries with a high burden of tuberculosis, most patients receive treatment in the private sector. We evaluated a multifaceted case-detection strategy in Karachi, Pakistan, targeting the private sector., Methods: A year-long communications campaign advised people with 2 weeks or more of productive cough to seek care at one of 54 private family medical clinics or a private hospital that was also a national tuberculosis programme (NTP) reporting centre. Community laypeople participated as screeners, using an interactive algorithm on mobile phones to assess patients and visitors in family-clinic waiting areas and the hospital's outpatient department. Screeners received cash incentives for case detection. Patients with suspected tuberculosis also came directly to the hospital's tuberculosis clinic (self-referrals) or were referred there (referrals). The primary outcome was the change (from 2010 to 2011) in tuberculosis notifications to the NTP in the intervention area compared with that in an adjacent control area., Findings: Screeners assessed 388,196 individuals at family clinics and 81,700 at Indus Hospital's outpatient department from January-December, 2011. A total of 2416 tuberculosis cases were detected and notified via the NTP reporting centre at Indus Hospital: 603 through family clinics, 273 through the outpatient department, 1020 from self-referrals, and 520 from referrals. In the intervention area overall, tuberculosis case notification to the NTP increased two times (from 1569 to 3140 cases) from 2010 to 2011--a 2·21 times increase (95% CI 1·93-2·53) relative to the change in number of case notifications in the control area. From 2010 to 2011, pulmonary tuberculosis notifications at Indus Hospital increased by 3·77 times for adults and 7·32 times for children., Interpretation: Novel approaches to tuberculosis case-finding involving the private sector and using laypeople, mobile phone software and incentives, and communication campaigns can substantially increase case notification in dense urban settings., Funding: TB REACH, Stop TB Partnership., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Objective: Evaluation and assessment of response rate, duration and toxicity in patients subjected to 5-FU based chemotherapy., Background: The therapeutic ratio shifts with different 5FU/LV regimens and none yet serve as the internationally accepted Gold Standard. A bimonthly regimen of high dose leucovorin is reported to be less toxic and more effective than monthly low dose regimens. We here compare therapeutic responses and survival benefit of the two regimens in poor prognosis patients with advanced colorectal carcinoma., Patients and Methods: A total of 35 patients with histologically confirmed colorectal carcinoma were subjected to de Gramont and Mayo Clinic regimen. Nineteen patients were treated with high dose folinic acid (200 mg/m2), glucose 5%, 5-FU (400 mg/m2) and 22 hr. CIV (600 mg/m2) for two consecutive days every two weeks. These patients had failed responses to previous chemotherapy and were above sixty years of age with poor general status. Sixteen patients (six below 60 years) with progressive disease were subjected to low dose folinic acid (20 mg/m2)for five days, 5FU(425 mg/m2) injection bolus for 5 days, every five weeks. An initial evaluation was made in sixty days and responders were reevaluated at sixty days interval or earlier in case of clinical impairment. Based on positive prognosis, the therapy was continued. Evaluation of treatment response was made on the basis of WHO criteria., Results: The response rate was 44% in thirty four evaluable patients, with 4 complete responses (11.8%) and 11 (32.4%) partial responses. The two schedules were well tolerated, whereas, mild toxicity without WHO Grade ≥ 2 events was assessed. The response duration was extended (12 months) in a few patients with age above sixty years treated by high dose bimonthly regimen of 5FU/LV., Conclusion: The regimens are safe and effective in advanced colorectal carcinoma patients with poor general status.

Changing environmental conditions have increased the transmission period for both dengue and malaria. Annual incidence of malaria in 2006 alone was 247 million cases leading to nearly 881 000 deaths; whereas another 50 to 100 million dengue infections, associated with an overall mortality of 2.5%, are expected each year. In Pakistan, like many developing nations with endemic malaria, an empirical clinical diagnosis is usually made, due to a lack of resources and availability of diagnostic facilities. Since both diseases are endemic in the same population and presenting symptoms are similar a thorough knowledge of both diseases is essential for improving diagnosis on clinical grounds. Thus our study aims were to evaluate knowledge, attitudes and practices of family medicine practitioners with regard to dengue and malaria and thereby assess the need for further training. Ninety consenting general practitioners (GPs) in different towns of Karachi, Pakistan were administered an extensive questionnaire of 50 questions regarding their knowledge, attitudes and practices on management of dengue and malaria. The authors concluded that despite possessing basic knowledge of the disease, the majority of GPs in the area needed training regarding both diseases and their management. Key targets identified for training programs included clinical diagnosis and management of endemic vector borne diseases.

The IRF-1 protein, a mammalian transcriptional factor encoded by a gene located in 5q23-q31, has antioncogenic properties. Involved in regulation of differentiation and proliferation, IRF-1 acts as a tumor suppressor gene and is inactivated by deletion of its one or more exons (exon skipping) in many hematological malignancies, including acute myelocytic leukemia (AML) and myelodysplastic syndromes (MDS). DNA samples, extracted from peripheral blood, taken from 50 Kashmiri AML subjects, were analysed using the polymerase chain reaction and compared with examples of age and gender matched healthy controls from the same population. Three different exon regions (2, 3 and 4) of the IRF-1 gene that were previously shown to be prone to deletion were selected for amplification and analysis. Deletion was observed in 31(62%) out of 50 AML patients (p=0.016). Exon 3 was most frequently deleted (58%), followed by exon 2 (28%), while exon 4 was least affected (12%), providing insights into critical roles in leukemogenesis. The number of deleted exons was variable, but single exon deletions were more frequent (30%). Of interest, IRF-1 gene deletions were not observed in 19 (38%) patients. In our study, the frequency of deletions of these three exons was slightly higher than in an Indian population (52%), but lower than in Sweden in Europe (95%). This study also explored the prevalence and clinical profile of IRF-1 deletions in AML patients. Adults had a significantly higher incidence than children (p=0.0168) and IRF-1 deletions were associated with low Hb (p< 0.0001), high TLC (p=0.0033) and a low platelet count (p=0.0076).

ECRG1 (esophageal cancer related gene 1) is a novel candidate member of the tumor suppressor gene family previously found to be down regulated in human esophageal cancer (ESCC). So far no evidence regarding the role of the ECRG1 gene in this cancer has been reported from the Kashmir valley, located on the border of the high risk 'esophageal cancer belt'. A case control study was therefore carried out with genomic DNA from 165 newly diagnosed ESCC patients (cases) and 200 control subjects. DNA was analyzed for ECRG1 polymorphisms by RFLP PCR, gel electrophoresis and direct sequencing. A statistically significantly increased risk of ESCC was found to be associated with the ECRG1 Arg/Gln and Gln/Gln genotype occurrence compared to the Arg/Arg genotype (odds ratio (OR) 1.698, 95% confidence interval (CI) 1.112-2.593); P= 0.0138) was observed. Statistically significant results were also obtained between the ECRG1 polymorphism and histophathological grade, smoking, dysphagia, low fruit/vegetable intake and salt tea consumption.

Background: Mistreatment or belittlement of medical students either by faculty or fellow students has often been reported. Perception of mistreatment has also been associated with increased degree of psychological morbidity. There is a lack of such studies being conducted amongst the medical students of Pakistan. The aim of this study was to determine the prevalence and forms of perceived mistreatment and presence of mental health morbidity in a private medical school in Pakistan. Also, any association between mental health morbidity and mistreatment was to be identified., Methods: A cross sectional study was carried out on medical students from Aga Khan University Hospital, Karachi, Pakistan during the period of June-September 2007. A self administered questionnaire, adapted from Frank et al and Baldwin et al was distributed to a total of 350 students. The questionnaire consisted of three parts: the first dealing with the demographics of the population, the second concerning the various forms of mistreatment, while the third assessed the mental health of students using the General Health Questionnaire 12(GHQ12). Descriptive statistics were performed. The Chi-square test and Fisher's exact tests were applied., Results: A total of 350 students were approached out of which 232 completed the questionnaire giving a response rate of 66.2%. Mistreatment was reported by 62.5% (145/232) of the respondents. Of these, 69.7% (83/145) were males and 54.9% (62/145) were females. There was a significant relationship between gender, year division, stress at medical school and possible use of drugs/alcohol and reported mistreatment but no statistical relationship was seen with psychiatric morbidity. The overall prevalence of psychological morbidity was 34.8% (77/221)., Conclusion: This study suggests high prevalence of perceived mistreatment and psychological morbidity among Pakistani medical students. However, no association was found between these two aspects of medical student education. There is a need to bring about changes to make the medical education environment conducive to learning. Increased student feedback, support systems and guidance about progress throughout the year and the provision of adequate learning resources may provide help with resolving both of these issues.

Objective: To know the present status of family systems in Pakistan, changes they are undergoing and implications of such trends on health of the elderly population., Methods: A cross-sectional study was carried out at the out-patient clinics, AgaKhan University Hospital, using convenience sampling method. Verbal informed consent was taken from the participants. The questions included demographic profile, satisfaction with current family system, opinions about changing trends of family systems, and their implications on health. Analysis was done using SPSS 13.0., Results: Four hundred subjects aged 65 and above were interviewed, out of which 226 (56.5%) were living in the joint family system (JFS), whereas 174 (43.5%) were living in a nuclear family system (NFS). A total of 77.5% respondents were in the age class of 65-70 years (mean=69). Majority were men (78%), married (78%), retired (55.8%) and with education below intermediate (61.8%). A total of 366 (91.5%) respondents were satisfied with their family system. 326 (81.5%) respondents said that the trend in family systems in Pakistan was changing and 318 (97.5%) of these subjects thought that it was a JFS to NFS trend. A decline in the proportion of JFS was seen with subsequent generations. 340 (85%) subjects said that a family system has a significant impact on health care., Conclusion: We have identified changing trends in family systems in Pakistan. Satisfaction with family system and the opinion about the role of a family system on healthcare is documented.

We determined the hepatitis C virus (HCV) genotypes and the co-infection rate with hepatitis G (HGV) in 32 Arab patients infected with hepatitis C virus. Twenty two Saudi and ten Egyptian patients were recruited from southern Saudi Arabia, an endemic region for chronic liver disease. HCV genotype was determined by PCR with genotype specific primers in the core region. Hepatitis G virus RNA was detected by the reverse-transcription polymerase chain reaction (RT-PCR). Five patients were blood donors, 11 patients had chronic hepatitis C infection, 13 had cirrhosis and 3 had cirrhosis with hepatocellular carcinoma. HCV genotype 4 was detected in 11 of 22 Saudi patients (50%). HCV genotype 1b was detected in 9 Saudi patients (40.9%) and HCV genotype 1a was detected in 2 Saudi patients (9.1%). Amongst the 10 Egyptian patients, HCV genotype 4 was found in 9 patients (90%)) and genotype 1b in 1 patient (10%). The co-infection rate of HGV was 31% in patients with HCV infection. We conclude that HCV genotypes 4 and 1b are the major pathogenic strains, accounting for greater than 90% of HCV across ethnic groups in the southern region of Saudi Arabia. There was no significant association between HCV genotype, age and severity of liver disease. Co-infection with HGV is common and the significance is indeterminate.

It is demonstrated first that staff explanations of problem behaviour can be reliably coded using a modified form of the Attributional Style Questionnaire; and second, that staff explanations are related through staff optimism to anticipated helping behaviour. This supports the hypothesis that, in professional staff, an important determinant of helping is optimism arising from attributions of a patient's problems. The influence of affective judgements, as emphasized in Weiner's (1986) theory of helping behaviour, is not supported.

Of 188 (144 renal, 29 bladder, 15 ureteric) stones analysed, 109 (58%) were pure calcium oxalate stones and in 177 (94%) calcium oxalate was the main component. The remaining were of mixed composition containing calcium phosphate, uric acid and calcium hydrogen phosphate. Serum calcium levels in 50 patients with pure calcium oxalate stones were normal. Majority of the cases (76%) came from the hilly areas of N.W.F.P.

Psammoma bodies associated with cancer cells of ovarian and endometrial origins have been previously described in cervicovaginal smears, as have psammoma bodies from totally benign processes. We describe the presence of numerous psammoma bodies in the cervical smear, endometrial curettage, and peritoneal wash specimens from a patient with subsequently discovered bilateral, ovarian, borderline serous tumors. We morphologically traced the transit of these psammoma bodies and their associated cytologically benign tumor cells through the entire female genital tract.