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Objectives: Patients with cerebral venous thrombosis (CVT) may present with early intracerebral hemorrhage (EICH). The objective of this study was to identify predictors for EICH in CVT patients via a systematic review and meta-analysis of observational studies. Additionally, we aimed to evaluate the clinical outcomes associated with the presence of EICH in these patients., Methods: Literature search on PubMed, EMBASE and Cochrane Library databases from inception up to 1 February 2024 was conducted. Five studies with predictors of EICH were included in qualitative synthesis and meta-analysis., Results: Pooled analysis demonstrated a statistically significant association between female gender and EICH (odd ratios (OR) = 1.51, 95 % confidence interval (CI) = 1.23-1.85, p < 0.01). The ICH patients had higher likelihood of seizures (OR = 3.07, 95 % CI = 1.69-5.58, p < 0.01), focal neurological deficits (OR = 4.07, 95 % CI = 2.57-6.44, p < 0.01), and decreased level of consciousness (OR = 3.89, 95 % CI = 2.53-5.87, p < 0.01). Superior Sagittal Sinus thrombosis was associated with higher likelihood of EICH (OR: 1.49, 95 % CI 1.05-2.13, P = 0.03). No statistically significant association was demonstrated between presence of EICH and pregnancy, presence of hematological diseases or thrombophilia, or other site of venous thrombosis (deep venous system, or multiple sinuses involvement). Furthermore, patients who exhibited early EICH were notably less likely to attain a favorable functional outcome (mRS 0-2) (OR: 0.28; 95 % CI 0.16-0.49; p < 0.001)., Conclusion: This meta-analysis demonstrates that among CVT patients, female patients with new onset seizures, focal neurological deficits and decreased level of consciousness are more likely to present with EICH., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Purpose: To highlight challenges and cancer care disparities in patients of diffuse large B-cell lymphoma management in resource-constrained settings., Materials and Methods: This multicenter retrospective study included 738 patients from 12 public and private sector hematology-oncology centers across Pakistan. Patients were divided into limited-resource and enhanced-resource settings as per national diffuse large B-cell lymphoma (DLBCL) guidelines., Results: The median age at diagnosis was 47 years (range, 14-89). Male:female ratio was 2.5:1. Majority of the patients (69.3%) were treated in limited-resource settings. Computed tomography was used as a staging modality in 442 (60%) patients. Limited-stage DLBCL was present in 13.5% of patients, while 86.3% had advanced-stage disease at diagnosis. First-line regimens included rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in 56% and cyclophosphamide, doxorubicin, vincristine, prednisone in 34% of patients, while 10% of patients received palliative regimens upfront. Of evaluable data, complete remission was documented in 299 (74.4%) patients, 39 (9.8%) had partial response and 63 (13.5%) had progressive disease. Disease-free survival (DFS) and overall survival (OS) status were not available for 345 (46.8%) patients at the time of data collection. Overall study cohort had a median follow-up of 2.2 years with a median OS of 3.6 years (95% CI, 3.1 to 4.1), median DFS of 3.1 years (95% CI, 2.6 to 3.6), and a 5-year OS of 40% and DFS of 36%., Conclusion: Patients from low- and middle-income countries present at an earlier age and have more advanced disease. Patients were frequently lost to follow-up, and record keeping was inadequate more so in patients treated in limited-resource settings. There is a need to establish a national lymphoma registry, improve record keeping, and standardize treatments to ensure improvement in treatment outcomes.

Background Radiology reports are important medico-legal documents facilitating communication between radiologists and referring doctors. Language clarity and precision are crucial for effective communication in these reports. Radiology reporting has changed with the evolution of imaging technology, prompting the adoption of precise terminology. Diagnostic certainty phrases (DCPs) play an important role in communicating diagnostic confidence in radiology reports. Objective The aim of this study was to evaluate the use of DCPs in radiology reports, before and after targeted educational interventions. Materials and methods The study was approved by the Aga Khan University Hospital's Ethical Review Committee and includes cross-sectional radiology reports. It involved three cycles of retrospective evaluation, with educational interventions in between to improve the use of DCPs. Results The study found a dynamic shift in the use of DCPs during the three cycles. Initially, intermediate-certainty phrases prevailed, followed by an increase in high-certainty phrases and a drop in low-certainty phrases. Later cycles showed a significant decline in DCPs and an increase in the use of definitive language. Across all subspecialties, there was a consistent decrease in intermediate- and low-certainty DCPs. Conclusion The study validates the transformative impact of educational interventions on the use of DCPs in radiology reports. The radiology reports frequently used DCPs with intermediate to low diagnostic certainty with improvement in the subsequent cycles of the study after educational interventions. It emphasizes the significance of continuing education to ensure the use of precise nomenclature., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Zafar et al.)

Introduction Non-alcoholic fatty liver disease (NAFLD) is the most prevalent liver condition worldwide. NAFLD has been associated with metabolic syndrome and its symptoms, such as type 2 diabetes, hypertension, dyslipidemia, and obesity. Ultrasound is widely used to grade hepatic steatosis, being the most cost-effective, non-invasive, and readily available modality without radiation exposure. The study aimed to assess the correlation of NAFLD grade as seen on ultrasound with blood parameters in a Pakistani population. Materials and methods The included patients were those who were diagnosed with fatty liver disease on ultrasound and whose laboratory tests were available within two weeks of the ultrasound. Two seasoned radiologists rated the severity of NAFLD after looking over ultrasound scans. Consecutive sampling technique was used to minimize selection bias. The degree and direction of the linear relationship between the NAFLD grade and each biochemical parameter were measured using the Pearson correlation coefficient. Results There were 207 patients in all who had been identified with NAFLD on ultrasound, the majority of whom had grade II NAFLD and were in their sixth decade of life. According to Pearson's analysis, the grade of NAFLD had larger positive associations with triglycerides, total cholesterol, low-density lipoprotein, and fasting blood sugar. High density lipoprotein and C-reactive protein were found to have a negative correlation with the grade of NAFLD. Conclusion The findings of the study highlight the correlation between NAFLD grade on ultrasonography and specific blood parameters, implying that managing these biochemical indicators may help to improve hepatic steatosis., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Zafar et al.)

Objective: Pain following the insertion of separators and archwires varies with age, sex, race, ethnicity, threshold, and health status. This study aimed to evaluate the characteristics of pain in orthodontic patients after the insertion of elastomeric separators, its effects on daily life, and its association with age and sex in a population not previously studied in this regard., Methods: A cross-sectional study of 130 patients undergoing orthodontic treatment included collecting data on demographics, pain experienced following the placement of separators, time of onset, duration, characteristics, change in dietary pattern or chewing side, intake of analgesics, and severity of pain on the Wong Baker's scale. The results are reported as counts and percentages. Associations between sex and age were evaluated using Pearson's chi-square test., Results: Among the 130 patients, 56.2% were 9-20 years old, 63.8% experienced pain following the insertion of separators, 22.9% had their first episode of pain at 4 hours, 56.6% experienced intermittent pain, and 37.3% experienced discomfort; 18.1% males and 81.9% females experienced pain following the insertion of separators. Pearson's chi-square test showed a significant association between pain and sex ( P = 0.04). Most patients (37.3%) reported "hurts little more" for pain intensity on Wong Baker's scale and 21.7% reported all four quadrants as sites of pain., Conclusions: The pain experienced after separator insertion was associated with sex and age. Females experienced more pain than males and patients between the age range of 21 and 36 years suffered more pain during mastication than between 9 and 20 years old.

To evaluate the bite force (BF) changes in bilateral cleft lip and palate (BCLP) in contrast to the non BCLP children after ALT-RAMEC Facemask therapy., The prospective study was carried out on a total of 60 subjects of age 6 to 13 years in a tertiary care hospital; treatment group, 30 children with BCLP and control group, 30 children without cleft lip and palate. Each cleft patient was received ALT-RAMEC Facemask treatment and their BF assessed at 4 different stages. Bite force taken before treatment, immediately, 3 months and 6 months after treatment. Bite force of the control group was taken at baseline to compare with the treatment group to demonstrate the difference in BF values. Independent t test and analysis of variance were used to perform statistical analysis., There was a significant difference in BF between the treatment group (BCLP) 122.53 ± 8.64 N and the control group (non BCLP) 181.38 ± 18.84 N at baseline. After the Alt RAMEC protocol, changes in BF recorded over 3 and 6 months of therapy showed significant improvement. The mean values of BF at 3months and 6 months were 106.7 ± 9.3 N and 137.4 ± 9.5 N, respectively., Bite force was significantly improved after ALT-RAMEC protocol followed by facemask therapy in BCLP patients.

Background: The illness known as "mask-mouth syndrome," which is brought on by constantly covering one's mouth and nose with a mask, was particularly prevalent among healthcare personnel. The covid-19 pandemic, however, had far-reaching effects on people's daily lives all around the world, to the point where mask use became practically mandatory. With Covid-19 posing a new threat to dental health, this study aims to assess the public's awareness of the issue and investigate how wearing a facemask affects oral hygiene., Methods: Cross-sectional research was conducted at Karachi's Jinnah Medical & Dental College. From February to May of 2022, it was carried out in the Dental Opd. A survey of 400 people was conducted, representing a cross-section of society in terms of age, gender, occupation, and other criteria. The poll had 11 closed-ended questions. The data was analyzed using SPSS 24. Descriptive analysis was used to examine the responses., Results: Men made up 44.5% (n = 174) of responses and women 56.5% (n = 226). Mean participant age was 27.31, ranging from 18 to 50. 99% (n = 396) of respondents wear masks. 48% (n = 192) of participants were uncomfortable using facemasks. Disposable face masks were voted the best option by 60.5% of respondents (n = 242). Negative effects or conditions brought on by mask use, such as halitosis (47.3%, n = 189) and dehydration (64.3%, n = 257)., Conclusion: Mask-mouth syndrome can occur as a result of using a face mask for prolonged periods of time. Mask benefits outweigh the danger of mask mouth syndrome., Competing Interests: None., (© 2022 The Authors.)

Background: COVID-19, a viral infection, has negatively impacted the physical and psychological health of the people worldwide. This was a descriptive, cross-sectional study, which aimed to investigate orthodontic postgraduate residents' knowledge regarding COVID-19, its association with anxiety around quality of their training, and performance of routine orthodontic procedures during the pandemic. A questionnaire was circulated online through WhatsApp to the orthodontic residents enrolled in the four-year postgraduate training program across the country which comprised the following sections: demographic data, questions to test knowledge of COVID-19, self-grading of anxiety around performing routine orthodontic procedures, academic aspects of the training program, and residents' thoughts on the current status of their training program in general during the pandemic. The residents were grouped based on their awareness on COVID-19, with >70% score taken as having adequate knowledge and ≤70% as inadequately updated. The association between COVID-19-related knowledge and the anxiety level of the residents experienced during training was assessed. Results were analyzed using SPSS (Statistical Package for Social Sciences) version 23.0. Counts and percentages were reported on baseline characteristics of studied samples. Descriptive methods were used to report the outcomes of this survey on knowledge of COVID-19, anxiety around performing orthodontic procedures, and different academic aspects of training. Statistical significance was set at p < 0.05 using the Pearson chi square test., Results: Most of the residents (51.5%) were adequately updated about the COVID-19 virus. Increased awareness was associated with more anxiety about the following: contracting the virus ( p < 0.01), performing different orthodontic procedures ( p < 0.05), disturbed patients' appointments ( p < 0.01), timely completion of their cases ( p < 0.01), and exam's preparation ( p =0.04). The group with <70% COVID-19 related knowledge opted for extension of their training period (51.8%)., Conclusion: COVID-19 related knowledge was clearly associated with anxiety experienced by the orthodontic residents during training in the pandemic. Awareness regarding the infection led to more anxiety around working during the pandemic, preparing for postgraduate exams, and concerns about its negative influence on the overall quality of the training program., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Hareem Sultan et al.)

Modular construction is considered as a preferred construction method over conventional construction due to a number of benefits including reduction in project completion time, improved environmental performance, better quality, enhanced workers' safety and flexibility. However, successful implementation of modular construction is hindered by various risk factors and uncertainties. Therefore, it is imperative to perform a comprehensive risk assessment of critical risk factors that pose a negative impact on the implementation of modular construction. Moreover, there is also a relatively less rate of modular construction adoption in developing countries, highlighting the need to focus more on underdeveloped regions. This study aims to propose a risk assessment framework for identification, evaluation and prioritization of critical risk factors affecting the implementation of modular construction in Pakistan. 20 risk factors were identified from previous literature which were then evaluated to shortlist the most significant risks using Fuzzy Delphi. The most significant risk factors were then prioritized using a novel Full-Consistency Method (FUCOM). The results specified 'Inadequate skills and experience in modular construction', 'Inadequate capacity of modular manufacturers' and 'Inability to make changes in design during the construction stage' as top three critical risks in the implementation of modular construction. This is the first study to propose a risk assessment framework for modular construction in Pakistan. The results of the study are useful to provide insights to construction industry practitioners in highlighting and eliminating risks involved in modular construction planning and execution., Competing Interests: The authors have declared that no competing interests exist.

Objective: To evaluate the awareness of emergency trauma management and the potential role of dentists in handling tooth avulsion injuries., Methods: The cross-sectional study was conducted at the Dental Outpatients Department of Jinnah Medical and Dental College, Karachi, from December 2020 to March 2021, and comprised dentists and final year dental students of either gender. Data was collected using a 17-item questionnaire to assess the awareness level regarding the knowledge of traumatic dental emergencies and the role of a dentist in handling a traumatic tooth injury. Data was analysed using SPSS 20., Results: Of the 170 subjects, 52(30.5%) were males and 118(69.4%) were females. Overall, 139(81.8%) subjects had prior knowledge regarding avulsion, 164(96.5%) were aware of the term avulsed tooth, 106(62.4%) considered milk to be the best transport media for an avulsed tooth, 159(93.5%) knew the significance of extra-oral time, and all 170(100%) subjects said they wanted to study more about dental traumatic injuries., Conclusions: There was adequate knowledge about the term avulsion, transport media and extra-oral time, and there was evidence of interest about learning more among the subjects.

Background: Patients with gastrointestinal angiodysplasia (GIA)-related bleeding are at high risk for readmissions, resulting in significant morbidity and an economic burden on the healthcare system., Aim: The aim of the study was to determine the 30-day readmission rate with reasons, predictors, and costs associated with GIA-related bleeding in the USA., Methods: We queried the National Readmission Database to identify patients hospitalized with GIA-related bleeding in the year 2016 using the International Classification of Diseases, Tenth Revision (ICD-10) codes. Primary outcomes included the 30-day readmission rate, and secondary outcomes were in-hospital mortality and resource utilization for index and re-hospitalizations. We also performed univariate and multivariate cox regression analysis to identify predictors of readmissions., Results: A total of 25 079 index hospitalizations for GIA-related bleeding were identified in 2016. Out of these, 5047 (20.34%) patients got readmitted within the next 30 days. The most common diagnosis associated with readmissions were related to recurrent gastrointestinal bleeding. Readmissions compared to index hospitalization has significantly higher length of stay (5.38 vs. 5.11 days, P = 0.03), but mean hospitalization charges ($52 114 vs. $49 691, P = 0.11) and mean total hospitalization costs ($12 870 vs. $12 405, P = 0.16) were similar. Patients with multiple co-morbidities, length of stay >5 days, and end-stage renal disease were found to be independent predictors for 30-day readmissions., Conclusion: Our study shows that one in five patients hospitalized with GIA-related bleeding was readmitted within 30 days of index hospitalization, placing a heavy economic burden on the healthcare system. Further research identifying strategies to reduce readmissions in these patients is needed., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To assess the frequency of maxillary ectopic canine both buccally and palatally displaced with incisor root resorption and dental agenesis., Methods: The cross-sectional study was conducted from April 8 to June 29, 2019, at the Department of Orthodontics, Dr. Ishrat Ul Ebad Khan Institute of Oral Health Sciences, and Dow Dental College, Dow University Of Health Sciences, Karachi, and comprised orthodontic patients diagnosed with maxillary ectopic canine eruption. Root resorption and agenesis were diagnosed on panoramic films. Root resorption was further confirmed by periapical radiographs. Data was analysed using SPSS 21., Results: Of the 98 subjects, 86(87.8%) had buccally displaced canines of which 38(44.2%) were associated with root resorption, while 12(12.2%) patients had palatally displaced canines of which 10(83.3%) had root resorption (p=0.011). Overall, 30(30.6%) lateral incisors were resorbed, 7(7.1%) both central and lateral incisors, 5(5.1%) premolars, and 6(6.1%) both lateral incisors and premolars were resorbed. Agenesis was detected in 10 (10.2%) subjects (p=0.62)., Conclusions: There was found to be no association of maxillary ectopic canines with incisor root resorption and dental agenesis.

Chronic diseases, as their name suggests, are progressive and can have overlapping features. Similar to this, Alzheimer's disease (AD) and diabetes mellitus (DM) fall into the category of chronic degenerative diseases. The global burden of these two ailments is manifold; hence, it seems important to view the pathophysiologic mechanisms of DM in the worsening of AD. Genetic as well as environmental factors are seen to play a role in the disease pathogenesis. Several genes, metabolic pathways, electrolytes, and dietary habits are seen to hasten brain atrophy. Lying behind this is the accumulation of amyloid precursor and tau - the misfolded proteins - within the brain substance. This mechanism is usually innate to AD itself, but the impact of insulin resistance, disturbing the homeostatic milieu, is seen as a powerful contributing factor aggravating the neuronal loss impairing an individual's memory. Since this neuronal loss is permanent, it may lead to complications as seen with AD. To reach a consensus, we conducted an electronic literature review search using different databases. This aided us in understanding the common aspects between AD and DM on genetic, molecular, cellular levels, as well as the impact of minerals and diet on the disease manifestation. We also found that despite exceptional work, additional efforts are needed to explore the relationship between the two entities. This will help physicians, researchers, and pharmaceuticals to frame remedies targeting the cause and avoid the progression of AD., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Nisar et al.)

Competing Interests: There are no conflicts of interest.

Coronavirus disease-2019 (COVID-19), first reported in China during December of 2019, is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection later spread very rapidly around the globe with over 8,708,008 cases reported, including more than 461,715 deaths reported across at least 216 countries by June 20, 2020. It was declared as a global pandemic by the World Health Organization (WHO) on March 11, 2020. With the rapidly increasing number of positive cases and deaths, there is a dire need for effective treatment. An urgent unmet need led to the planning and opening of multiple drug development trials for treatment and vaccine development. In this article, we have compiled comprehensive data on many candidate drugs such as remdesivir, favipiravir, ribavirin, umifenovir, arbidol, lopinavir, ritonavir, baricitinib, hydroxychloroquine, nitazoxanide, azithromycin, baloxavir, oseltamivir, losartan, and tocilizumab. We have tabulated available data on various clinical trials testing various aspects of COVID-19 therapeutics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Neupane et al.)

Headaches due to migraine are the second leading cause of disability in the world. Migraine can be classified as episodic migraine (EM) and chronic migraine (CM). The course of the disease starts from an aura followed by 4-72 hours of bouts of throbbing, mostly unilateral headache associated with nausea, photo/phonophobia with/without neurological deficit. The pathophysiology of migraine remains debatable and many drugs are used to help control migraine attacks with little or no benefit. However, patient compliance remains a reason for over and underdosing of these medications. The calcitonin gene-related peptide (CGRP), a vasoactive peptide is known to contribute to the disease course. Much work is done on antagonizing the receptor or the molecule itself. For this purpose, genetically engineered monoclonal antibodies are being utilized for long-term reduction in morbidity and prevention of migraine headaches. The four to name are: galcanezumab, fremanezumab, eptinezumab, and erenumab. The purpose of this review is to shed light on the use of these monoclonal antibodies, completed and recruiting trials, and the role of these medications in the prevention of not only EM and CM but also in medication overuse headaches., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2020, Pervez et al.)

Inflammatory bowel disease (IBD) is a constellation of devastating chronic inflammatory changes in the bowel, either involving the large or small bowel or part of both. As it is widely diagnosed in the fertile age group, this disorder can present itself, very commonly, during pregnancy and thus a better understanding of the disease can be an important factor to influence the maternal and fetal well-being. Medications are what is considered the first line in the management of this disease to control the symptoms or keep the disease in remission. In addition to this, the drugs used to keep the disease in remission can also cause significant adverse effects on the patient and the new nurturing life preparing itself for the outside world. What the fetus gets from the mother will stay for life with the child. We conducted an electronic literature review search which highlights the significance and impact of sustained remission of IBD and the cautious use of various drugs during pregnancy for that purpose. In addition to the influences already mentioned, It is evident that nutritional deficiencies can also prevail with the advancing disease, something to manage as a side note as well. These deficiencies can have a definite effect on the fetus and may cause developmental malformations. In order to avoid this process, a systemic and joint approach should be curtailed. This can reduce the adverse outcomes associated with this ailment during pregnancy., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2019, Pervez et al.)

A series of fifteen N4-benzyl substituted 5-chloroisatin-3-thiosemicarbazones 5a-o were synthesized and screened mainly for their antiurease and antiglycation effects. Lemna aequinocitalis growth and Artemia salina assays were carried out to determine their phytotoxicity and cytotoxicity potential. All the compounds proved to be extremely effective urease inhibitors, demonstrating enzyme inhibition much better than the reference inhibitor, thiourea (IC50 values 1.31 ± 0.06 to 3.24 ± 0.15 vs. 22.3 ± 1.12 μM). On the other hand, eight out of fifteen compounds tested, i.e. 5b, 5c, 5h-k, 5m and 5n were found to be potent glycation inhibitors. Of these, five viz. 5c, 5h-j and 5n proved to be exceedingly efficient, displaying glycation inhibition greater than the reference inhibitor, rutin (IC50 values 114.51 ± 1.08 to 229.94 ± 3.40 vs. 294.5 ± 1.5 μM).

A series of fifteen N 4 -benzyl substituted 5-nitroisatin-3-thiosemicarbazones 5a-o was synthesized and evaluated for urease inhibitory, phytotoxic and cytotoxic influences. All the compounds proved to be highly potent inhibitors of the enzyme, showing inhibitory activity (IC 50 =0.87±0.25-8.09±0.23μM) much better than the reference inhibitor, thiourea (IC 50 =22.3±1.12μM) and may thus act as persuasive leads for further studies. In phytotoxicity assay, twelve out of fifteen thiosemicarbazones tested i.e. 5a-e, 5g, 5i and 5k-o appeared to be active, exhibiting weak or non-significant (5-35%) growth inhibition at the highest tested concentrations (1000 or 500μg/mL). In contrast, only one compound i.e. 5i was active in the brine shrimp (Artemia salina) lethality bioassay, demonstrating cytotoxic activity with LD 50 value 2.55×10 -5 M. Molecular docking studies of compounds 5a-o were also performed to identify their probable binding modes in the active site of the enzyme., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

In recent years, the development and use of polymeric nanocomposites in creating advanced materials has expanded exponentially. A substantial amount of research has been done in order to design polymeric nanocomposites in a safe and efficient manner. In the present study, the impact of processing parameters, such as, barrel temperature, and residence time on the mechanical and thermal properties of high density polyethylene (HDPE)-TiO₂ nanocomposites were investigated. Additionally, scanning electron microscopy and X-ray diffraction spectroscopy were used to analyze the dispersion, location, and phase morphology of TiO₂ on the HDPE matrix. Mechanical tests revealed that tensile strength of the fabricated HDPE-TiO₂ nanocomposites ranged between 22.53 and 26.30 MPa, while the Young's modulus showed a consistent increase as the barrel temperature increased from 150 °C to 300 °C. Moreover, the thermal stability decreased as the barrel temperature increased.

The current study presents an investigation on the optimization of injection molding parameters of HDPE/TiO₂ nanocomposites using grey relational analysis with the Taguchi method. Four control factors, including filler concentration (i.e., TiO₂), barrel temperature, residence time and holding time, were chosen at three different levels of each. Mechanical properties, such as yield strength, Young's modulus and elongation, were selected as the performance targets. Nine experimental runs were carried out based on the Taguchi L₉ orthogonal array, and the data were processed according to the grey relational steps. The optimal process parameters were found based on the average responses of the grey relational grades, and the ideal operating conditions were found to be a filler concentration of 5 wt % TiO₂, a barrel temperature of 225 °C, a residence time of 30 min and a holding time of 20 s. Moreover, analysis of variance (ANOVA) has also been applied to identify the most significant factor, and the percentage of TiO₂ nanoparticles was found to have the most significant effect on the properties of the HDPE/TiO₂ nanocomposites fabricated through the injection molding process.

Background: Pyruvate dehydrogenase (PDH) activity is altered in many human disorders. Current methods require tissue samples and yield inconsistent results. We describe a modified method for measuring PDH activity from isolated human peripheral blood mononuclear cells (PBMCs). RESULTS/METHODOLOGY: We found that PDH activity and quantity can be successfully measured in human PBMCs. Freeze-thaw cycles cannot efficiently disrupt the mitochondrial membrane. Processing time of up to 20 h does not affect PDH activity with proteinase inhibitor addition and a detergent concentration of 3.3% showed maximum yield. Sample protein concentration is correlated to PDH activity and quantity in human PBMCs from healthy subjects., Conclusion: Measuring PDH activity from PBMCs is a novel, easy and less invasive way to further understand the role of PDH in human disease.

A series of 29 previously reported N(4)-substituted 5-nitroisatin-3-thiosemicarbazones 2-30 has been screened for leishmanicidal potential. Compounds 2-4, 7, 8, 10-13, 15-19, 21, 23, 24, 26, 28 and 30 exhibited good to excellent antileishmanial activities with IC50 values ranging from 0.44 ± 0.02 to 32.38 ± 0.66 µg/mL. Of these, 5, 7, 19 and 28 proved to be the most active antileishmanial agents, displaying activities with IC50 values 1.78 ± 0.35, 0.44 ± 0.02, 1.91 ± 0.04 and 4.28 ± 0.75 µg/mL, respectively, which were even better than the standard drug, pentamidine (IC50 = 5.09 ± 0.04 µg/mL). This study presents the first example of exhibition of leishmanicidal potential by isatin-thiosemicarbazones and as such furnishes a solid basis for further research on these compounds to develop more potent antileishmanial agents.

Artemisinin (ARMN) is a potent antimalarial drug, which is effective against multidrug resistant strains of Plasmodium falciparum and produces rapid recovery even in patients with cerebral malaria. Being poorly soluble in water, artemisinin is incompletely absorbed after oral intake due to poor dissolution characteristics in the intestinal fluids. To enhance these properties, solid dispersions of artemisinin with succinic acid (SUC) were prepared using drug-carrier ratios 1 : 1, 1 : 4, 1 : 6, 1 : 8 and 1 : 10 by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), Fourier transform infrared spectroscopy (FTIR), x-ray diffraction patterns (XRD), phase solubility and dissolution kinetics evaluated by applying zero order, first order, Higuchi, and Korsmeyer-Peppas models. Physical mixtures produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. The dissolution profiles of all formulations followed Higuchi model and exhibited diffusion-controlled release of drug. Solvent evaporation method (SLVPs) exhibited improved solubility and freeze dried solid dispersions (FDSDs) produced highest solubility but stability constant was opposite. ARMN and SUC both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed reduced intensity in their XRD patterns while solid dispersions by SLVPs exhibited twice reduced intensity and much displaced angles, whereas FDSDs showed synergistic effects in some of ARMN and SUC peaks. DSC thermograms of FDSDs at drug-carrier ratios 1 : 1-1 : 4 showed lower melting temperature and enthalpy change (deltaH) values than respective SLVPs, whereas at higher ratios, a reverse was true. SLVPs showed displaced methyl stretching bands at lower drug-carrier ratios and exhibited O-H stretching characteristic bands of SUC at higher drug-carrier ratios. In addition, carbonyl group and C-O stretching vibrations characteristic of SUC (1307 cm(-1)) appeared prominently compared to PMs, whereas C-O stretching characteristic bands of ARMN disappeared at higher ratios. FDSDs exhibited distinct nature of bonding compared to respective SLVPs and PMs.

Background: Obstructed labour with ruptured uterus is a serious obstetrical complication with a high incidence of maternal and foetal morbidity and mortality. This study was conducted to find out the incidence of uterine rupture particularly in the patients of obstructed labour (OL), foeto-maternal outcome of such patients, and its management., Methods: This two year descriptive study was conducted in the Department of Obstetrics and Gynaecology Unit-I, at Muhammad Medical College Hospital from 1st January 2007 to 31st December 2008, on 40 diagnosed cases of OL. Patients were admitted through Casualty or were admitted in ward. Patients with previous caesarean section and myomectomy were excluded., Results: Ruptured uterus was found in 8 out of 40 patients of obstructed labour, they were relatively elder and grand-multiparous. Mean age of the patients was 36.5 years, while parity ranged between 5 and 12. Only one (12.5%) patient was primigravida with mean gestational age of 39.15 weeks. Seven (87.5%) patients had abdominal pain and tenderness, 5 (62.5%) vaginal bleeding, and 2 (25%) had shock. All cases were immediately managed with fluid replacement, blood transfusion and surgery. Six (75%) cases were diagnosed as ruptured uterus on clinical features while 2 (25%) with incomplete rupture were diagnosed on caesarean section for obstructed labour. Foetal mortality rate was high (7, 87.5%); 5 (62.5%) were fresh stillbirth and 2 (12.5%) died in nursery. Only 1 (12.5%) baby survived. There was 1 maternal death due to puerperal sepsis., Conclusion: The incidence of rupture uterus in obstructed labour was 20%. Immediate intervention is important factor for successful management of uterine rupture.

In the title compound, C(16)H(13)ClN(4)OS, the isatin ring system is oriented at dihedral angles of 10.60 (7) and 72.60 (3)° with respect to the thio-semicarbazide and 2-chloro-benzyl groups, respectively. The near planarity of the isatin and thio-semicarbazide groups [r.m.s. deviations of 0.0420 and 0.0163 Å, respectively] is reinforced by intra-molecular N-H⋯O and N-H⋯N hydrogen bonds, which generate S(6) and S(5) rings, respectively. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. Aromatic π-π stacking inter-actions between the centroids of heterocyclic five-membered and benzene rings [distance = 3.6866 (11) Å] are also observed.

A new series of sixteen N4-aryl substituted 5-chloroisatin-3-thiosemicarbazones 2a-2p has been synthesized, characterized and tested for selected biological activities i.e. cytotoxicity, phytotoxicity and urease inhibition. In the brine shrimp bioassay, all the synthesized compounds gave LD50 values>2.30x10(-4) M-2.79x10(-4) M and were, therefore, found to be almost inactive, whereas in phytotoxicity assay, regardless of the nature of aryl substituents, they displayed weak to moderate (5-40%) phytotoxic activity at the highest tested concentrations (500 or 1000 μg/mL). In urease inhibition bioassay, compounds 2a, 2c, 2e, 2f, 2k and 2m exhibited relatively a higher degree of urease inhibition with IC50 values ranging from 38.91 μM to 76.65 μM and thus proved to be potent inhibitors of the enzyme. Of these, 2f and 2m displayed pronounced inhibition with IC50 values 38.91 μM and 39.50 μM, respectively, and may act as lead compounds for further studies. Structure-activity relationship (SAR) studies revealed that electronic effects of the substituents about the phenyl ring at N4 of the thiosemicarbazone moiety played an important role in enhancing the urease inhibitory potential of some of the synthesized compounds.

Artemisinin (ARMN) is a drug of choice against drug-resistant malaria especially due to Plasmodium falciparum. Being poorly soluble in water, its solid dispersions with nicotinamide (NA) were prepared at various drug-carrier ratios (1:1, 1:4, 1:6, 1:8, 1:10) by solvent evaporation and freeze drying methods. These solid dispersions were characterized by differential scanning calorimetery (DSC), fourier transform infrared spectroscopy (FTIR), X-ray diffraction patterns (XRD), phase solubility and dissolution studies. Artemisinin and nicotinamide both were found completely crystalline as shown by their XRD patterns. Physical mixtures (PMs) showed decreased intensity in their XRD patterns while solid dispersions by solvent evaporation method (SLVPs) exhibited displaced angles and decreased intensity whereas freeze dried solid dispersions (FDSDs) showed least number of peaks having low intensity and maximum displaced angles. DSC thermograms of drug-carrier ratios at 1:1-1:4 showed lower melting temperature than artemisinin and nicotinamide in all preparations. Endothermic temperature of artemisinin in PMs and SLVPs increased with rise of nicotinamide content upto 1:6 ratio followed by decline. All samples showed crystallization temperature below the artemisinin except drug-carrier ratio 1:6 of PMs while δH value was minimum at this ratio. FDSDs produced lowest endothermic temperature than corresponding PMs and SLVPs. SLVPs exhibited band shifting in both functional and fingerprint region compared to respective PMs as exhibited by their FTIR spectra. FDSDs and SLVPs showed different nature of bonding among artemisinin and nicotinamide. FDSDs produced strongest CONH(2) bonding followed by SLVPs and PMs respectively. PMs produced significantly higher aqueous solubility and rate of dissolution as compared to artemisinin alone. SLVPs exhibited improved solubility and dissolution profile corresponding to PMs. FDSDs showed highest release rate and aqueous solubility followed by SLVPs and PMs at all ratios. PMs and SLVPs showed their highest dissolution profile at 1:6 drug-carrier ratio followed by gradual decrease while FDSDs progressed in dissolution rate with increase of nicotinamide content successively upto maximum at 1:10 ratio.

In the title compound, C(15)H(10)FN(5)O(3)S, an intra-molecular N-H⋯N hydrogen bond generates an S(5) ring, whereas N-H⋯O and C-H⋯S inter-actions complete S(6) ring motifs. The dihedral angle between the isatin ring system and the fluoro-benzene ring is 5.96 (6)° and the complete mol-ecule is close to planar (r.m.s. deviation for all the non-H atoms = 0.112 Å). In the crystal, mol-ecules are linked by N-H⋯O hydrogen bonds to form C(8) chains along the [100] direction and C-H⋯O inter-actions are also observed.

A series of twenty one N4-aryl substituted 5-trifluoromethoxyisatin-3-thiosemicarbazones 3a-3u was synthesized by the reaction of trifluoromethoxyisatin 1 with different arylthiosemicarbazides 2 in aqueous ethanol (50%), containing a few drops of acetic acid. Their structures were established on the basis of analytical (CHN) and spectral (IR, 1H-NMR, EIMS) data. All the synthesized compounds were evaluated for their toxicity potential by a brine shrimp lethality bioassay. Ten compounds i.e., 3a, 3e, 3i-3l and 3n-3q proved to be active in this assay, displaying promising toxicity (LD50 = 1.11 × 10-5 M - 1.80 × 10-4 M). Amongst these, 3k, 3n and 3o were found to be the most active ones (LD50 = 1.11 × 10-5 M - 1.43 × 10-5 M). Compound 3k showed the highest activity with a LD50 value of 1.11 × 10-5 M and can, therefore, be used as a lead for further studies. Structure-activity relationship (SAR) studies revealed that the presence of strong inductively electron-attracting trifluoromethoxy substituent at position-5 of the isatin moiety played an important role in inducing or enhancing toxic potentiality of some of the synthesized compounds.

In the title compound, C(15)H(11)FN(4)OS, there are three independent mol-ecules, each with a disordered 3-fluoro-phenyl group [occupancy ratios = 0.547 (17):0.453 (17), 0.645 (5):0.355 (5) and 0.626 (15):0.374 (15)] and displaying dihedral angles of 4.2 (3), 25.2 (6) and 32.4 (5)° between the 2-oxoindoline and fluoro-substituted phenyl rings. Strong intra-molecular N-H⋯N and N-H⋯O and weak intra-molecular C-H⋯S hydrogen bonds complete S(5) and S(6) ring motifs, while strong inter-molecular N-H⋯O hydrogen bonds inter-connect the three independent mol-ecules through R(3) (3)(12) ring motifs. The three-mol-ecule units are in turn linked into polymeric sheets via C-H⋯F and C-H⋯S hydrogen bonds and π-π inter-actions [centroid-centroid distances in the range 3.520 (2)-3.820 (9) Å].

The crystal structure of the title compound, C(16)H(11)F(3)N(4)O(2)S, is stabilized in the form of polymeric chains by N-H⋯O inter-actions. In the mol-ecular structure, two S(5) ring motifs are formed by intra-molecular N-H⋯N and N-H⋯O hydrogen bonding and two S(6) rings are present due to N-H⋯O and C-H⋯S inter-actions. π-π inter-actions are present with distances of 3.2735 (17), 3.563 (2) and 3.664 (4)/3.688 (3) Å between the centroids of the heterocyclic rings, between the centroids of the heterocyclic ring and trifluoro-meth-oxy-substituted phenyl ring, and between the centroids of the trifluoro-meth-oxy-substituted phenyl rings, respectively. The trifluoro-meth-oxy-phenyl group is disordered over two sites with an occupancy ratio of 0.642 (10):0.358 (10).

In the title compound, C(16)H(11)F(3)N(4)OS, the dihedral angle between the aromatic ring systems is 69.15 (10)°. Intra-molecular N-H⋯N and N-H⋯O hydrogen bonds generate S(5) and S(6) rings, respectively. A short N-H⋯F contact also occurs. In the crystal, inversion dimers linked by pairs of N-H⋯O hydrogen bonds generate R(2) (2)(8) loops. The dimers are linked by N-H⋯F hydrogen bonds, forming polymeric chains propagating in [100]. π-π inter-actions also exist between the centroids of the benzene rings of the 2-oxoindoline group at a distance of 3.543 (3) Å and a short C=O⋯π contact occurs. Two F atoms of the trifluoro-methyl group are disordered over two sets of sites in a 0.517 (8):0.483 (8) ratio.