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The aim of the current study was to develop and evaluate the therapeutic potential of apocynin (APO) loaded pH-sensitive nanoparticles (NPs) based transdermal hydrogel for management of rheumatoid arthritis (RA). Slightly modified nanoprecipitation technique was used for preparation of polymeric nanoparticles. Optimization was done through design expert software. Optimized APO-NPs were loaded into carbopol-934 based hydrogel as final dosage form and further studied for physicochemical properties. Optimized APO-NPs formulation had a minimum particle size 63.44 nm, polydisperibility index 0.161, and zeta potential -15mV with a maximum encapsulation efficiency of 89%. In-vitro and ex-vivo studies of APO-NPs based hydrogel was performed at pH 5.5 (pH of normal skin) and 6.8 (pH of inflammed joint) showed a pH-responsive sustained drug release and increased penetration in comparison to free APO based hydrogel. The stability studies of APO-NPs based hydrogel were done to strengthen the potential use of the prepared formulation through transdermal route. Assessment and therapeutic efficacy of the prepared pH-sensitive nanocarriers system was evaluated in chronic inflammatory RA mice model. Parameters associated with chronic inflammation were investigated including behavioral changes and histopathological, and radiological x-rays images of joints of mice paws. In-vivo study depicts improvement in behavioral parameter, decline in synovial hyperplasia and bone structure restoration. In conclusion, APO loaded pH-sensitive NPs based transdermal is a promising carrier system that can effectively manage RA.

Graphical abstract, Highlights • Skin cancer is a fatal public health concern rising continuously all over the world. • Several environmental and genetic risk factors are associated with cutaneous carcinogenesis. • Use of nanocarriers for targeted delivery of anticancer agents is the most advanced approach. • Polymeric structures are suitable for tumor selective delivery of drugs, genes and imaging agents. • Polymeric micro/nanostructures have successfully used for combination anticancer therapies., Background Skin cancer has been the leading type of cancer worldwide. Melanoma and non-melanoma skin cancers are now the most common types of skin cancer that have been reached to epidemic proportion. Based on the rapid prevalence of skin cancers, and lack of efficient drug delivery systems, it is essential to surge the possible ways to prevent or cure the disease. Aim of review Although surgical modalities and therapies have been made great progress in recent years, however, there is still an urgent need to alleviate its increased burden. Hence, understanding the precise pathophysiological signaling mechanisms and all other factors of such skin insults will be beneficial for the development of more efficient therapies. Key scientific concepts of review In this review, we explained new understandings about onset and development of skin cancer and described its management via polymeric micro/nano carriers-based therapies, highlighting the current key bottlenecks and future prospective in this field. In therapeutic drug/gene delivery approaches, polymeric carriers-based system is the most promising strategy. This review discusses that how polymers have successfully been exploited for development of micro/nanosized systems for efficient delivery of anticancer genes and drugs overcoming all the barriers and limitations associated with available conventional therapies. In addition to drug/gene delivery, intelligent polymeric nanocarriers platforms have also been established for combination anticancer therapies including photodynamic and photothermal, and for theranostic applications. This portfolio of latest approaches could promote the blooming growth of research and their clinical availability.

A strain of Aspergillus niger NRRL 337 degrade agro-industrial waste i.e wheat bran in solid state fermentation and produce esterase enzyme. Maximum enzyme activity 15.2 U/ml was produced after 72 h of incubation at 30˚C. The protein was partially purified by performing ammonium sulfate precipitation and immobilized metal ion chromatography (IMAC) technique. SDS-PAGE analysis showed molecular weight of esterase was 70 kDa. Effects of different nitrogrn and carbon sources with different concentrations were also studied. Partially purified enzyme was active at pH of 6.0 for up to 3 h and at temperature of 70˚C for 1 h. Ca2+, Mg2+, Na+1, and K+1 play an important role in increasing enzyme activity. The residual activity of esterase was decreased in the presence of organic solvents. SDS, β-mercaptoethanol, and DMSO are good inhibitors for esterase enzyme. Under these conditions, partially purified esterase with specific activity of 114.20 U/mg and 47.58 purification fold was obtained. The data achieved from this work are important in terms of heat stability and pH of esterase and giving a new enzyme source for industrial applications.

Background: Multidrug-resistant tuberculosis (MDR-TB) is a growing public health problem. Treatment regimens used against MDR-TB are costly, prolonged, and associated with more side effects as compared with the drug-susceptible tuberculosis. This study was framed to determine the incidence of adverse drug events, risk factors, and their management in MDR-TB patients.Methods: This prospective follow-up cohort study was conducted at the site of programmatic management of drug-resistant TB located at the Pakistan Institute of Medical Sciences, Islamabad. All patients, irrespective of their age, gender, and ethnicity, were included in the study. Adverse drug events were observed in patients at different time points during the study. Patients enrolled for the treatment from January 2018 were prospectively followed till December 2020 up to their end treatment outcomes.Results: Out of 126 MDR-TB patients enrolled for treatment, 116 met the inclusion criteria and were included in the final analysis. Most patients (50.9%) were between 18 and 45 years of age. A minimum of one adverse event was experienced by (50.9%) patients. Of all the adverse events, gastrointestinal disorders were more frequent (47.4%), followed by arthralgia (28.4%) and psychiatric disturbance (20.6%). Furthermore, multivariate analysis showed a significant association with the incidence of adverse events in patients with age group above 60 years (odds ratio (OR) 4.50; 95% CI 1.05-19.2), active smokers (OR 4.20; 95% CI 1.31-13.4), delayed reporting to the TB center (OR 4.03; 95% CI 1.34-12.1), and treatment without bedaquiline regime (OR 3.54; 95% CI 1.23-10.1). Most of the patients (94.6%), counseled by the pharmacist, were found to be satisfied with the information provided and looked for more pharmacist counseling opportunities in the management of MDR-TB.Conclusion: Current findings recommend that ADEs might be well managed by timely identification and reporting. Bedaquiline coupled with other active medications lowered the chance of ADEs in MDR-TB patients. Elderly patients, active smoking behavior, and those who have a delay in the treatment initiation are more prone to ADEs. Clinical pharmacist’s contribution to TB control programs may help caregivers and patients concerning the rational use of medication, early detection, and management of ADEs.

Objective: This study was aimed to investigate TB patients adherence and treatment outcomes among internally displaced patients in comparison with adjacent settled areas. Methods: The study was designed as an observational cross-sectional study among the TB patients of internally displaced populations (IDPs) of North Waziristan Agency (NWA) and adjacent settled areas of Bannu and Lakki Marwat (NIDPs). Based on the study inclusion and exclusion criteria 330 patients fullfilled the inclusion criteria and were assigned equally to both IDPs and NIDPs study groups. Odds ratio (OR) with 95% confidence interval was calculated and p-values, 0.05 were considered statistically significant. Results: The treatment outcomes with the status of “cured” and “completed treatment” were better among NIDPs as compared to IDPs. Patients with treatment outcome status of “defaulted treatment”, “without documentary evidence, and “failure” were high in IDPs as compared to NIDPs. Adherence to TB treatment was better among NIDPs (50.9%) as compared to IDPs (39.4%). The patients showing non-adherence to TB treatment were more among IDPS (27.3%) than NIDPs (10.9%). Conclusion: Overall results of this study revealed a poor adherence to the TB treatment medications with an odds ratio of 0.286, (p

Stimuli responsive nanocarriers proved to be an efficient system in accurate diagnosis and targeted delivery of therapeutic moieties. Enzymes have been researched widely as successful targeting age...

This study aimed to utilise the proficient function of diacerein (DCR) and anti-inflammatory polymers to develop sustained release nanoencapsulated emulgel for potential use in osteoarthritis (OA).Chitosan (CHS) and chondroitin sulphate (CS) were employed as natural anti-inflammatory polymers to encapsulate nanoformulation of DCR. Optimised nanoformulation was prepared and characterised by investigating impact of polymers and surfactant on particle size, PDI, and encapsulation efficiency (EE). Afterwards, nanoemulgel of optimised DCR-NPs was formulated and evaluated for transdermal application.Optimised nanoformulation depicted spherical shape with particle size of 320 nm having PDI and EE of 0.3 ± 0.07 and 82 ± 4% (w/w), respectively. DCR-nanoemulgel depicts sustained action of drug up to 96 h with enhanced permeation activity and non-irritancy index.The elaborated nanoemulgel sustained release of drug having superior penetration properties with provision of enhanced therapeutic effect owing to the presence of CHS, CS, and Argan oil possessing indelible anti-inflammatory attributes.

Prophylactic use of antibiotics before surgery is evidence-based practice for prevention of surgical site infections (SSIs).To investigate adherence to and surgeons' perception of antibiotic prophylaxis guidelines.A two-phase, cross-sectional prospective study conducted in two teaching hospitals. Phase 1: 6-month audit of prescriptions to investigate adherence rate to evidence-based guidelines. The important information was collected from medical charts through a predesigned proforma. Phase 2: self-administration questionnaire was used to investigate the surgeons' perception. Descriptive statistics, independent-sample Kruskal-Wallis test and multivariate linear regression analysis were performed using SPSS version 21.0.A total of 866 eligible surgical cases (acute appendectomy; n = 418; 48.2%), laparoscopic cholecystectomy (n = 278; 32.1%) and inguinal hernia (n = 170; 19.7%) were investigated. Surgical antibiotic prophylaxis was prescribed in 97.5% of procedures. Out of these, 9.5% adhered to guidelines with respect to correct choice, 40% for timing, and 100% for dose and route (optimal value 100%). Most patients received ceftriaxone (n = 503; 59.5%) as prophylactic antibiotic. The questionnaire (good internal consistency; α ≥ 0.7) was filled out by 200 surgeons. More than half (69%) of participants thought that antibiotics were overused. Most surgeons perceive that poor adherence to treatment guidelines is due to poor awareness, underestimation of infection, lack of consensus, and disagreement with guidelines recommendations.Surgeons have positive perception that antibiotics should be used according to guidelines recommendations. However, we found poor treatment adherence to antibiotic prophylaxis guidelines.مراجعة استعمال المضادات الحيوية الوقائية ومدى امتثال الجراحين للمبادئ التوجيهية القياسية في الإجراءات الجراحية المعتادة في منطقة البطن.ذاكر خان، نافيد أحمد، شايستا ظفار، عاصم الرحمن، فايز الله خان، محمد صقلان، سُهيل قامران، حاضر رحمن.يُعتبر استعمال المضادات الحيوية على سبيل الوقاية قبل الجراحة من الممارسات المُسنَدة بالبيّنات للوقاية من حدوث عدوى المواضع الجراحية.هدفت هذه الدراسة إلى تحرّي مدى الامتثال للمبادئ التوجيهية الخاصة باستعمال المضادات الحيوية الوقائية ومنظور الجراحين في هذا الشأن.أُجريت دراسة استباقية مقطعية على مرحلتين في اثنين من المستشفيات الجامعية. المرحلة 1: مراجعة الوصفات الطبية التي حُررت على مدار 6 أشهر لتحري معدل الامتثال بالمبادئ التوجيهية المُسنَدة بالبيّنات. وجُعت المعلومات المهمة من المخططات الطبية للمرضى باستخدام استمارة مُصمَّمة مسبقاً لهذا الغرض. المرحلة 2: استخدام استبيان يُستكمل ذاتياً لتحرِّي منظور الجراحين في هذا الشأن. وقد استُخدم الإصدار 21.0 من برنامج SPSS لإجراء إحصاءات وصفية، واختبار كروسكال واليس القائم على العينات المستقلة، وتحليل الانحدار الخطي المتعدد المتغيرات.بلغ مجموع الحالات الجراحية التي تصلح للخضوع لهذه الدراسة 866 حالة، تراوحت بين استئصال الزائدة الدودية الملتهبة التهاباً حاداً (العدد=418؛ 48.2٪)، واستئصال المرارة بالمنظار (العدد= 278؛ 32.1٪)، والفتق الأُربي (العدد=170؛ 19.7٪). وقد وُصفت المضادات الحيوية الوقائية في 97.5٪ من الإجراءات الجراحية. ومن بين هذه الإجراءات الجراحية، كانت نسبة الامتثال للمبادئ التوجيهية من حيث الاختيار الصحيح، والتوقيت، والجرعة والمسار 9.5٪، و 40٪، و 100٪ على التوالي (القيمة المُثلى 100٪). وتلقى معظم المرضى دواء سيفترياكسون (العدد= 503؛ 59.5٪)، بوصفه أحد المضادات الحيوية الوقائية. وقد أجاب عن الاستبيان 200 جراح (اتساق داخلي جيد؛ α ≥ 0.7). ورأى أكثر من نصف الجراحين المشاركين في الاستبيان (69 ٪) أن هناك زيادة في استعمال المضادات الحيوية. كما رأى معظم الجراحين أن السبب وراء ضعف الامتثال بالمبادئ التوجيهية للعلاج يرجع إلى ضعف الوعي، وعدم تقدير الحجم الحقيقي للعدوى، وغياب التوافق في الآراء، والاختلاف مع التوصيات الخاصة بالمبادئ التوجيهية.لدى الجراحين منظور إيجابي بشأن ضرورة استعمال المضادات الحيوية وفقاً لما ورد في التوصيات الخاصة بالمبادئ التوجيهية، لكن لوحظ ضعف الامتثال للمبادئ التوجيهية الخاصة بالعلاج بالمضادات الحيوية الوقائية.Audit de l’antibioprophylaxie et de l’observance des lignes directrices standard par les chirurgiens dans les actes courants de chirurgie abdominale.L’usage prophylactique des antibiotiques préalablement à un acte chirurgical est une pratique fondée sur des données probantes, qui permet de prévenir les infections du site opératoire (ISO).Étudier l’observance des lignes directrices en matière d’antibioprophylaxie et le point de vue des chirurgiens sur cette pratique.Une étude prospective transversale en deux phases, a été menée dans deux hôpitaux universitaires. Phase 1 : Audit des ordonnances sur six mois, afin d’évaluer le taux de d’observance des lignes directrices fondées sur des données probantes. Les informations importantes ont été recueillies à partir des dossiers médicaux au moyen d’un formulaire conçu à cet effet. Phase 2 : un auto-questionnaire a été utilisé pour étudier le point de vue des chirurgiens. Des statistiques descriptives ont été produites, un test de Kruskal-Wallis sur échantillons indépendants et une analyse de régression linéaire multivariée ont été réalisés à l’aide du logiciel SPPS, version 21.0.Au total, 866 cas chirurgicaux répondant aux critères de l’étude ont été examinés : appendicectomies aiguës, (n = 418, soit 48,2 %), cholécystectomies laparoscopiques, (n = 278, soit 32,1 %) et hernies inguinales (n = 170, soit 19,7 %). Une antibioprophylaxie chirurgicale a été prescrite dans 97,5 % des interventions. Parmi ces dernières, le respect des lignes directrices était de 9,5 % pour le choix de l’antibiotique, de 40 % pour le moment de l’administration et de 100 % pour la dose et la voie d’administration, la valeur optimale étant 100 %. La majorité des patients ont reçu de la ceftriaxone (n = 503, soit 59,5 %) comme antibiotique prophylactique. Le questionnaire a été rempli par 200 chirurgiens, avec une cohérence interne satisfaisante (α ≥ 0,7). Plus de la moitié (69 %) des participants estimaient que les antibiotiques étaient surutilisés. La majorité des chirurgiens pensent que l’observance médiocre des lignes directrices de traitement est due à un manque de sensibilisation, à une sous-estimation de l’infection, à l’absence d’un consensus et à un désaccord avec les recommandations de ces lignes directrices.Les chirurgiens approuvent l’usage des antibiotiques conformément aux recommandations des lignes directrices de traitement. Cependant, notre étude révèle une observance médiocre de ces textes dans les traitements d’antibioprophylaxie.

Methotrexate (MTX) is the first line agent for therapy against rheumatoid arthritis (RA); however, orally its efficacy is hampered by poor solubility, less permeability, short plasma half-life, and reduced bioavailability. Meanwhile, parenteral formulations are associated with severe adverse effects. In an attempt to improve the efficacy of MTX, we synthesized polycaprolactone-polyethylene glycol-polycaprolactone (PCL-PEG-PCL) triblock copolymer by a ring-opening copolymerization reaction and used it as a carrier for the fabrication of MTX-loaded nanomicelles. Surfactant-free, self-assembled nanomicelles were prepared by nanoprecipitation technique and optimized through central composite design. The optimized nanomicelles exhibited a size distribution of 31 nm and an encapsulation efficiency of 91%. In vitro, the nanomicelles exhibited hemocompatibility, sustained release, and significantly high uptake in lipopolysaccharide activated macrophages. To facilitate application on the skin, optimized nanomicelles were loaded into a Carbopol 934-based hydrogel with eucalyptus oil as a penetration enhancer. Eucalyptus oil significantly improved the permeation of nanomicelles through the skin (p < 0.001). When the hydrogel was applied on the RA mice model, nanomicelles exhibited preferentially highest accumulation in the inflamed joints than other organs. As compared with the free MTX, MTX nanomicelles significantly improved the pharmacokinetic (4.34-fold greater half-life, 3.68-fold higher AUC0-t, and 3.15-fold higher mean residence time) and pharmacodynamic profile ascertained through low inflammatory cytokines expression, improved oxidation protection, recovered behavioral responses, and radiological analysis. MTX nanomicelles-based hydrogel also significantly reduced the hepatotoxicity and did not activate the immune system. These results suggest that the MTX-loaded nanomicelles-based transdermal hydrogel can prove to be a promising agent against RA.

Snowballing levels of greenhouse gas emissions and concerns about climate change has led to an ongoing exploration of biofuels. Bioethanol can be obtained from wheat straw and can be readily available as clean fuel for combustion engines. Therefore, Wickerhamomyces anomalus yeast strain IHZ-26 was used to produce bioethanol from sugar solution obtained from enzymatic hydrolysis of wheat straw. Nineteen different fermentation media were used for this purpose in which carbon source employed was sugar solution obtained from enzymatic hydrolysis of wheat straw. Out of which, maximum bioethanol yield (1.09 g/L; p

Background: Foreign body ingestion by children is a commonly encountered problem and accounts for a significant emergency visits among pediatric population. Although these ingested foreign bodies pass spontaneously and uneventfully, a subset of such bodies may become trapped in the digestive tract, eventually leading to significant injury. Most of these bodies are radio-opaque and detectable radiologically, but some radio-lucent may become a diagnostic dilemma and subtle management issue. Case Report: We report a case of a one-year girl who presented after accidental ingestion of foreign body with signs and symptoms of acute intestinal obstruction. Initially we were unable to diagnose the cause, but later the radiological investigation suspected a mesenteric cyst. After failure to respond to conservative measures she underwent exploratory laparotomy, and a jelly ball was removed from the gut. The patient had uneventful post-operative recovery and was kept on follow-up for three months without any complication. Conclusion: These patients do not respond to conservative measures and need surgery on an emergency basis. It is likely that if left untreated may have caused Intestinal perforation and irreversible shock. Radiolucent foreign bodies are difficult to diagnose and need high level of suspicion. Need of the hour is to educate the parents to be extra vigilant as “prevention is better than cure”.

Sortilin-related vacuolar protein sorting 10 (VPS10) domain containing receptor 3 (SORCS3) is a neuron-specific transmembrane protein involved in the trafficking of proteins between intracellular vesicles and the plasma membrane. Genetic variation at SORCS3 is associated with multiple neuropsychiatric disorders and behavioural phenotypes. Here, we undertake a systematic search of published genome-wide association studies to identify and catalogue associations between SORCS3 and brain-related disorders and traits. We also generate a SORCS3 gene-set based on protein–protein interactions and investigate the contribution of this gene-set to the heritability of these phenotypes and its overlap with synaptic biology. Analysis of association signals at SORSC3 showed individual SNPs to be associated with multiple neuropsychiatric and neurodevelopmental brain-related disorders and traits that have an impact on the experience of feeling, emotion or mood or cognitive function, while multiple LD-independent SNPs were associated with the same phenotypes. Across these SNPs, alleles associated with the more favourable outcomes for each phenotype (e.g., decreased risk of neuropsychiatric illness) were associated with increased expression of the SORCS3 gene. The SORCS3 gene-set was enriched for heritability contributing to schizophrenia (SCZ), bipolar disorder (BPD), intelligence (IQ) and education attainment (EA). Eleven genes from the SORCS3 gene-set were associated with more than one of these phenotypes at the genome-wide level, with RBFOX1 associated with SCZ, IQ and EA. Functional annotation revealed that the SORCS3 gene-set is enriched for multiple ontologies related to the structure and function of synapses. Overall, we find many independent association signals at SORCS3 with brain-related disorders and traits, with the effect possibly mediated by reduced gene expression, resulting in a negative impact on synaptic function.

This study aims to determine UV-B resistance and to investigate computational analysis and antioxidant potential of methoxy-flavones of Micromonospora aurantiaca TMC-15 isolated from Thal Desert, Pakistan. The cellular extract was purified through solid phase extraction and UV-Vis spectrum analysis indicated absorption peaks at λmax 250 nm, 343 nm, and 380 nm that revealed the presence of methoxy-flavones named eupatilin and 5-hydroxyauranetin. The flavones were evaluated for their antioxidant as well as protein and lipid peroxidation inhibition potential using di(phenyl)-(2,4,6-trinitrophenyl) iminoazanium (DPPH), 2,4-dinitrophenyl hydrazine (DNPH), and thiobarbituric acid reactive substances (TBARS) assays, respectively. The methoxy-flavones were further studied for their docking affinity and interaction dynamics to determine their structural and energetic properties at atomic level. The antioxidant potential, protein and lipid oxidation inhibition and DNA damage preventive abilities were correlated as predicted by computational analysis. The eupatilin and 5-hydroxyauranetin binding potential to their targeted proteins 1N8Q and 1OG5 is -4.1 and -7.5 kcal/mol, respectively. Moreover, the eupatiline and 5-hydroxyauranetin complexes illustrate van der Waals contacts and strong hydrogen bonds to their respective enzymes target. Both in-vitro studies and computational analysis results revealed that methoxy-flavones of Micromonospora aurantiaca TMC-15 can be used against radiation mediated oxidative damages due to its kosmotrophic nature. The demonstration of good antioxidant activities not only protect DNA but also protein and lipid oxidation and therefore could be a good candidate in radio-protective drugs and as sunscreen due to its kosmotropic nature.

Major depressive disorder (MDD) is a common mental disorder generally characterized by symptoms associated with mood, pleasure and effectiveness in daily life activities. MDD is ranked as a major contributor to worldwide disability. The complex pathogenesis of MDD is not yet understood, and this is a major cause of failure to develop new therapies and MDD recurrence. Here we summarize the literature on existing hypotheses about the pathophysiological mechanisms of MDD. We describe the different approaches undertaken to understand the molecular mechanism of MDD using genetic data. Hundreds of loci have now been identified by large genome-wide association studies (GWAS). We describe these studies and how they have provided information on the biological processes, cell types, tissues and druggable targets that are enriched for MDD risk genes. We detail our understanding of the genetic correlations and causal relationships between MDD and many psychiatric and non-psychiatric disorders and traits. We highlight the challenges associated with genetic studies, including the complexity of MDD genetics in diverse populations and the need for a study of rare variants and new studies of gene-environment interactions.

Globally, every year, millions of surgical procedures are carried out and most of the patients experience surgical site infections (SSIs) after surgery. This general overview is aimed to find SSI incidence, risk factors, and treatment-related factors in the current scenario of literature searched. Articles from scientific databases such as Google Scholar, Medline, PubMed, and ScienceDirect were searched and extracted with keywords SSI’, surgery’, surgical infection’, wound infection’, Risk factors SSI’, Antibiotics, and Treatment. The incidence rate of SSIs is on rise in developing countries due to limited reporting which is alarming for patient safety. Various surgery-related guidelines might be helpful in the reduction of SSI incidence. A full assessment of patients before surgery are needed through various available parameters; especially, rational use of antibiotics may minimize the risk of misuse. Healthcare-associated infections need much attention and awareness as the situation is much alarming.

Surgical site infections (SSIs) are among the common problems associated with paediatric surgeries and significantly contribute to postsurgical morbidity and mortality. This study was conducted to assess antimicrobial prophylaxis practices and compliance rates with international guidelines in common paediatric surgical procedures. A retrospective cross-sectional study was conducted in paediatric patients aged

Background: appropriate prescribing of antimicrobial prophylaxis (AP) is a main strategy of the antimicrobial stewardship programme. Aim: to investigate the prescribing practices of antimicrobial prophylaxis and adherence to recommended protocols in older patients in the surgical wards at a 600-bed teaching hospital in Islamabad, Pakistan. Method: researchers selected 240 surgical procedures retrospectively for patients aged 65 years and older admitted to four surgical specialties (abdominal, orthopaedic, urological and neurosurgery) during 1 year. The different parameters of antimicrobial prescription were compared with international clinical practice guidelines. Findings: There were more ‘clean’ surgical wound procedures (n=104; 43.3%) than ‘clean contaminated’ (n=97; 40.4%) and most of these were elective surgical procedures (n=226; 94%). The indication, selection, route, dose, and timing of antimicrobial were found to have adhered with the standard guidelines in 89.6%, 32.5%, 100%, 100% and 55.3% of cases, respectively (optimal value 100%). A statistically significant difference was observed between antimicrobial practices and surgical procedures (P< 0.001). The commonly prescribed antimicrobials were ceftriaxone followed by cefazolin. Conclusion: about 89% of participants who underwent surgical procedures received antimicrobials. The selection of therapeutic agent, the timing and use of broad-spectrum antimicrobial were the common problems in our setting.

Objectives: To investigate the utilization pattern of Surgical antibiotic prophylaxis (SAP) for the prevention of surgical infections in most common abdominal and orthopedic surgical procedures. Methods : A prospective observational and non-intervention study was conducted at two teaching hospitals (PIMS and SIH) in Islamabad, Pakistan. Prescriptions records were reviewed to assess the utilization pattern of SAP during the nine-month duration. Data regarding most common surgical procedures, antimicrobial utilization, dose, route and administration timing of SAP were extracted for analysis. Observed practices were compared with standard treatment guidelines. Results : Out of total 1512 surgical procedures about, 56.9% (n=860) of patients performed abdominal followed by 652 (43.1%) orthopedic surgical procedures. A total of 212 (14%) surgical procedures were completely correct in all steps. SAP were given in 1474 (97.5%) of surgical procedures. In 712 of the participants (48.3%) were given Ceftriaxone following by Cefazolin (n=247, 16.7%). Abdominal surgeries were majorly managed with Ceftriaxone (59%) while the orthopedic surgeries managed with Ceftriaxone (31.3%) and Cefazolin (30%). Appropriate choice of SAP was observed in (n=275; 18.6%) procedures and about half (n=719, 49%) received antibiotics within optimal timing. The appropriate choice/selection of SAP according to the guidelines was greater in orthopedic surgical procedures (n=212; 14.8%) than abdominal surgeries (n=63; 4.3%); p≤0.001. Compliance with respect to timing was significantly lower in an orthopedic surgical procedure (n=301) as compared to abdominal surgeries (n=418); p≤0.001. Similarly, a statistically significant difference observed between PIMS and SIH with respect to SAP practices; p≤0.001. Conclusions : Inappropriate choice, the timing of administration and combination of SAP were observed in the current study. J Microbiol Infect Dis 2019; 9(3):104-111.

This study was conducted to investigate the antibiotic utilization pattern and patient care indicators according to the World Health Organization (WHO) methodology. An observational prospective and prescription-based study was conducted in the surgical outpatient department (SOD) and emergency department (ED) in two teaching hospitals during 3 months. Prescription of patients was investigated through random systematic sampling technique and desired information was collected through pre-design pro forma. Observed practices were evaluated according to WHO criteria. The categorical data were presented as percentages and the chi-squared test was used to make comparisons through SPSS V-22.0. A total of 586 prescriptions (hospital-A = 279; hospital-B = 307) were collected from the SOD and ED over the study period. There were more male patients (398; 67.9%) compared with female with an average age of 43.5 years (ranged 16–95). All the prescriptions contained antibiotics (100%) and the prescription having at least one injectable antibiotic were 300 (51.4%). Generic prescribing was observed in 13.5% of prescriptions and 96% of antibiotics were prescribed from the National Essential Medicine List/formulary. The mean time consumed and noted during a consultation and dispensing was found to be 8 min and 157.8 s, respectively. Furthermore, only 48% of the patients knew about the correct dosage schedule of the antibiotic prescription. Cephalosporins (mostly ceftriaxone and cefuroxime) were the most frequently prescribed class of antibiotics. The over-prescribing of antibiotics, low generic prescribing, lack of patients’ knowledge, a short consultation, and dispensing times were the major identified problems.

Sustainable bio-renewable energy source is a need of an hour to meet the rising global energy demands. Efficient conversion of fermentable sugars by yeast into bioethanol from lingo-cellulosic biomass is one of the most important attribute. In order to get temperature and ethanol tolerant yeast strain, one hundred and seventy one soil samples were collected from adjacent areas of various sugar mills located in Punjab, Pakistan. Fifty six yeast strains were isolated and primarily screened for bioethanol production. Maximum bioethanol producing (3.07 g/L) yeast strain IHZ-26 was identified by sequencing of 18S rRNA ITS region and identified as a new strain of Wickerhamomyces anomalus which was assigned GenBank accession number KT883963. This strain demonstrated substantial tolerance to ethanol (25%) and temperature (50°C) and have the ability to significantly ferment several sugars i.e. glucose, fructose, mannose, maltose, xylose and lactose. To the best of our knowledge, this is first report of multi stress tolerant Wickerhamomyces anomalus from Pakistan. This yeast with these distinct characteristics can be employed in bioethanol industry for more viable and economical process.

Monocytes are leading component of the mononuclear phagocytic system that play a key role in phagocytosis and removal of several kinds of microbes from the body. Monocytes are bone marrow precursor cells that stay in the blood for a few days and migrate towards tissues where they differentiate into macrophages. Monocytes can be used as a carrier for delivery of active agents into tissues, where other carriers have no significant access. Targeting monocytes is possible both through passive and active targeting, the former one is simply achieved by enhanced permeation and retention effect while the later one by attachment of ligands on the surface of the lipid-based particulate system. Monocytes have many receptors e.g., mannose, scavenger, integrins, cluster of differentiation 14 (CD14) and cluster of differentiation 36 (CD36). The ligands used against these receptors are peptides, lectins, antibodies, glycolipids, and glycoproteins. This review encloses extensive introduction of monocytes as a suitable carrier system for drug delivery, the design of lipid-based carrier system, possible ways for delivery of therapeutics to monocytes, and the role of monocytes in the treatment of life compromising diseases such as cancer, inflammation, stroke, etc.

Objective Biodegradable polymers are extensively used due to their efficient safety profiles. The aim of the current study was to fabricate, evaluate, and characterize biodegradable, biocompatible fluconazole (FLZ) loaded chitosan (CHS) chondroitin sulfate (CS) nanoparticles (NPs) for topical delivery. Polymers utilized in the formulation not only served as a carrier system but also aided in fighting with complex etiology of the disease due to their innate antifungal activities. Methods NPs were prepared by the complex coacervation method, then were optimized for various parameters and subsequently loaded into a cream. Results Scanning electron microscopic (SEM) analysis showed spherical morphology of the NPs. Prepared NPs showed an average particle size in the range of 350-450 nm and an encapsulation efficiency (EE) of 86%. The polydispersity index (PDI) was found to be 0.148 that showed a uniform distribution of NPs. Fourier transform infrared (FTIR) spectroscopy confirmed the absence of any electrostatic interaction between ingredients. In vitro drug release analyses exhibited a sustained release of the drug and higher antifungal activity than free FLZ. Ex vivo permeability and drug distribution in different skin layers ensured a site-specific delivery of the FLZ-NPs. As compared with free FLZ and other control groups, the prepared NPs also exhibited significantly higher antifungal activity against Candida albicans (p Conclusion It was concluded from the results that the FLZ-NPs laden cream could be a potential candidate for topical and site-specific delivery of the drug cargo for the potential treatment of fungal infections.

Muhammad Nasir Kalam,1 Muhammad Fawad Rasool,2 Faleh Alqahtani,3 Imran Imran,4 Asim Ur Rehman,1 Naveed Ahmed1 1Department of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, Pakistan; 2Department of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, Pakistan; 3Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh, 11451, Saudi Arabia; 4Department of Pharmacology, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, 60800, PakistanCorrespondence: Naveed AhmedDepartment of Pharmacy, Quaid-i-Azam University, Islamabad, 45320, PakistanTel +92 (51) 90644180Email natanoli@qau.edu.pkMuhammad Fawad RasoolDepartment of Pharmacy Practice, Faculty of Pharmacy, Bahauddin Zakariya University, Multan, PakistanTel +923008639046Email fawadrasool@bzu.edu.pkAim: The study was aimed to understand the underlying causes for the differences in propranolol pharmacokinetics (PK) between healthy and cirrhosis populations by using a systematic whole-body physiologically based pharmacokinetic (PBPK) model-building approach for suggesting model informed propranolol dosing in liver cirrhosis patients with different stages of disease severity.Methods: A whole-body PBPK model was developed by using population simulator PK-Sim® by using reported physicochemical and clinical data for propranolol in healthy and liver cirrhosis populations. The model evaluation was done by visual verification and comparison of PK parameters using their observed/predicted ratios (Robs/pred).Results: The developed model has effectively described the disposition of propranolol after intravenous and oral application in healthy and liver cirrhosis populations. All the model predictions were comparable to the observed clinical data and the Robs/pred for all the PK parameters were within a 2-fold range. A significant increase in plasma concentration of propranolol and decrease in drug clearance was observed in progressive stages of liver cirrhosis. The developed model after evaluation with the reported clinical PK data was used for suggesting model informed propranolol dosing in different stages of liver cirrhosis based on systemic unbound drug concentration.Conclusion: The developed PBPK model has successfully described propranolol PK in healthy and cirrhosis populations after IV and oral administration. The evaluated PBPK propranolol-cirrhosis model can have many implications in predicting propranolol dosing in liver cirrhosis patients with different stages of disease severity.Keywords: PBPK, propranolol, cirrhosis, dose adjustments, drug therapy

Polysaccharides, due to their outstanding properties, have attracted the attention of researchers, working in the biomedical field and especially of those working in drug delivery. Modified/functionalized polysaccharides further increase the importance for various applications. Delivery of therapeutics for diverse ailments in different endocrine glands and hormones safely, is a focal point of researchers working in the field. Among the routes followed, the transdermal route is preferred due to non-exposure of active moieties to the harsh gastric environment and first-pass metabolism. This review starts with the overview of polysaccharides used for the delivery of various therapeutic agents. Advantages of polysaccharides used in the transdermal route are addressed in detail. Types of polysaccharides will be elaborated through examples, and in this context, special emphasis will be on the polysaccharides being used for synthesis of the membranes/films. Techniques employed for their modification to design novel carriers for therapeutics delivery will also be discussed. The review will end with a brief discussion on recent developments and future perspectives for delivery of therapeutic agents, and vaccine development.

Nanotechnology is a ground breaking and innovative field when combined with tissue engineering (TE) offers great versatility in enhancing cell adhesion, growth differentiation, proliferation, and synthesis of extracellular matrix. TE comprises several materials, that is, polymeric, metallic, and carbon-based structures. Polymeric nanomaterials can be used to fabricate biomaterials due to their unique properties like biodegradation and biocompatibility. Both natural and synthetic polymers are either combined or coated as nanomaterials to form nano surfaces, nanocomposite, nanofibers, and other nanostructures that can be used in TE. Selective polymers are discussed with their physiochemical properties and their utilization in nano-based TE. Various forms of scaffold can be utilized along with growth factors and polymeric nanomaterials to constitute required tissue. Fabrication of nanomaterials is done by electrospinning, self-assembly, and phase separation. Polymeric nanomaterials are used in both hard tissue (dental, bone, and craniofacial) and soft tissue (cardiac, neural, and cartilage) engineering.

Chronic wound infections have become a challenging problem due to escalating antibiotic resistance and lack of viable delivery approaches. Carvacrol (CAR) has been reported to be effective against multidrug resistant pathogens. In this study, CAR was formulated into a site-specific nanoparticle (NP) delivery system using poly(caprolactone) (PCL) to achieve a sustained antimicrobial effect at infection sites. These NPs were further incorporated into dissolving microneedles (MNs) to facilitate painless application and overcome the necrotic tissue barrier which hinders drug penetration into wound bed. The release study exhibited significantly higher release of CAR from PCL NPs in the presence of bacteria, highlighting its potential for on-demand delivery. Moreover, encapsulation of CAR in PCL NPs resulted in 2–4 fold increase in its antimicrobial activity. Dermatokinetic studies revealed that CAR-PCL NPs-MNs were able to enhance skin retention of CAR after 24 h (83.8 ± 5.15%), compared to free CAR-MNs (7.3 ± 2.04%). Importantly, this novel approach exhibited effective antimicrobial activity in an ex-vivo wound model. Hence, these findings have proven the concept that loading of CAR into this advanced MNs platform can lead to sustained antimicrobial effect at desired site and may provide a novel effective approach for treatment of infected wounds. However, further studies must be conducted to investigate in-vivo efficacy of the developed system in an appropriate infection model.

Globally, surgical site infections are one of the common infections which lead to a large amount of mortality and morbidity in postsurgical care. The risk for surgical site infection is multidimensional which includes mainly; patient, surgery, and hospital-related factors. This study is aimed to determine the burden of SSIs along with contributed risk factors. A prospective observational cross-sectional study was conducted in one of the largest public-sector hospitals in Pakistan. A total of 412 patients were recruited in the study with full consent and monitored for 30 days after surgery with direct and indirect surveillance. Overall, in seven different surgical procedures the incidence (29.8%) rate of SSI was observed; in appendectomy ( n = 17, 4.1%), exploratory laparotomy ( n = 51, 12.6%), laparoscopic cholecystectomy ( n = 12, 2.90%), mesh repair ( n = 17, 4.01%), thyroidectomy (5, 1.2%), transurethral resection of the prostate ( n = 11, 2.6%), and transurethral resection of the bladder (10, 2.4%). The average SSI rate in every single procedure was about 18 (4.27%) per surgical procedure out of 123 (29.85%) SSI cases. Types of SSI identified were superficial, deep incisional and organ/space ( n = 76, 18.4%, n = 23, 5.5%, and n = 24, 5.7%). Incidence of SSIs during admission, at readmission, and post-surveillance cases were ( n = 50, 12.1%, n = 25, 6.0% and n = 48, 11.6%). Associated risk factors found contributed to the incidence of SSI ( p

Background and Objectives Liraglutide, an analog of human glucagon-like peptide 1 (GLP-1), has been approved for the treatment of type 2 diabetes mellitus in Pakistan since 2016. It is a GLP-1 receptor agonist that has shown promising results in terms of not only glycemic control but also weight loss. Our study aimed to provide evidence regarding the safety and effectiveness of liraglutide in Pakistan and to look at the adherence rate and treatment satisfaction of patients using liraglutide. Methods This is an observational retrospective study that recruited patients who were treated with liraglutide. Data were collected at the first visit and follow-up. Morisky Green Levine Adherence Scale and Treatment Satisfaction Questionnaire for Medication (TSQM-9) were used for the determination of adherence and satisfaction with the treatment. Results A total of 70 patients were recruited in the study, The mean difference in weight, body mass index, glycated hemoglobin (HbA1C), systolic blood pressure, and diastolic blood pressure from baseline to follow-up was -5.36 kg, -2.14 kg/m2, -1.76%, -12.38 mmHg, and 5.55 mmHg, respectively. Nausea was the main side effect reported. TSQM-9 scores were compared from baseline, and it was found that patients are satisfied with the treatment and its effectiveness. Conclusions Our study has demonstrated the effectiveness of liraglutide as a monotherapy or combination therapy in the Pakistani population. Liraglutide led to reduction in HbA1C and weight. This is associated with high treatment satisfaction rate and adherence rate. Thus, liraglutide remains an effective though expensive treatment option in a country like Pakistan.

At present, several drug molecules have been used for the treatment of rheumatoid arthritis (RA). However, the utilization of these compounds through the oral and parenteral route is limited due to low bioavailability, rapid metabolism, poor absorption, first-pass effect, and serious adverse effects. A transdermal delivery system is an appealing option in this scenario, as it possesses the proficiency to overcome drawbacks associated with the oral and parenteral route. With the innovation of several enhancement strategies, many therapeutic agents have been administered transdermally, proposing an exceptional approach to treat RA. The present article provides an insight into the etiology and pathophysiology of RA. The challenges of the transdermal route and the strategies to improve those problems are described. The current advances in increasing the transdermal efficiency of the therapeutics against RA are discussed. Limitations and advantages regarding the state of the art transdermal delivery system and future outlook are also summarized.

The current study aimed to formulate the clozapine (CLZ) loaded proniosomal (PN) gel and evaluate its in vitro release, ex vivo permeation and gel properties. CLZ is a BCS class II drug with low bi...

Background: A judicious utilization of antibiotic prophylaxis and postoperative analgesics are an effective strategy to prevent surgical site infections and pain, respectively. Aims: The aim of this study was to assess prescription practices and guidelines adherence of antibiotics and analgesics in total knee replacement (TKR) surgery. Setting and Design: A cohort observational pilot study was conducted for a period of 2 months at two tertiary care teaching hospital (government hospital = GH and private hospital = PH) in Islamabad, Pakistan. Subjects and Methods: All the individuals aged ≥18 who underwent TKR surgery with no previous surgery and infection (n = 300) were included during the study period. The patient medication profile was analyzed through various indicators. International evidence-based guidelines were used as a reference to analyze current treatment practices. Statistical Analysis Used: Descriptive statistics such as frequencies, percentages, averages, standard deviation, and Chi-square test was used for interpretation of data in SPSS V-22.0. Results: Preoperative prophylactic antibiotics were prescribed in 94% (n = 283) cases. Of these, 61.5% adhered according to guidelines with respect to correct choice, 64.6% for timing, and 100% for the route (optimal value 100%). The prescribing behavior with respect to antibiotic choice and timing was different among GH and PH hospitals (P = 0.001). Cefazolin was the most commonly prescribed preoperative and postoperative antibiotic, followed by cefuroxime. With respect to analgesics, paracetamol and tramadol were frequently used in TKR patients. One hundred and seventy six (58.6%) patients received analgesics according to the guidlines recommendations, and 7.8% (n = 23) received more than one analgesic in their postoperative prescription. Conclusion: The low compliance rate with guidelines was observed. The choice and timing of antibiotic, selection of analgesics, and its multiple usage were main identified problems.