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Background: Limited data exist on the role of coronary collaterals circulation (CCC) in patients with ST-elevation acute coronary syndrome (STE-ACS). This study aimed to assess CCC and the in-hospital course of patients with CCC undergoing primary percutaneous coronary intervention (pPCI). Methods: The study included consecutive STE-ACS patients undergoing pPCI. Good CCC was defined as Rentrop collateral score (RCS) of 2–3. Patients with good and poor CCC were compared regarding clinical characteristics, angiographic patterns, and hospital course. Results: In the sample of 4683 patients, mean age was 55.6 ± 11 years, and 78.8 % were male. Good CCC was observed in 499 (10.7 %) patients. The rate of intra-procedure slow-flow/no-reflow (SF/NR) was 29.9 % vs. 20.5 % (p

The clinical advancement of protein-based nanomedicine has revolutionized medical professionals' perspectives on cancer therapy. Protein-based nanoparticles have been exploited as attractive vehicles for cancer nanomedicine due to their unique properties derived from naturally biomacromolecules with superior biocompatibility and pharmaceutical features. Furthermore, the successful translation of Abraxane™ (paclitaxel-based albumin nanoparticles) into clinical application opened a new avenue for protein-based cancer nanomedicine. In this mini-review article, we demonstrate the rational design and recent progress of protein-based nanoparticles along with their applications in cancer diagnosis and therapy from recent literature. The current challenges and hurdles that hinder clinical application of protein-based nanoparticles are highlighted. Finally, future perspectives for translating protein-based nanoparticles into clinic are identified.

Biomimetic nanoparticles represent a promising avenue for mitigating rapid clearance by the reticuloendothelial system (RES); however, current challenges include insufficient tumour targeting, suboptimal adhesion, and inadequate localized drug release within tumour regions. These shortcomings contribute to persistent contests, such as recurrence and pulmonary metastasis, even with advanced breast cancer therapies. Stimuli-sensitive drug release can furbish the membrane coated nanoparticles for their efficiency against the stated problems. To enhance the efficacy of biomimetic nanoparticles in addressing these issues, we proposed a versatile, stimuli-responsive drug delivery system by encapsulating doxorubicin (Dox) and perfluorohexane (PFH) within poly (lactic-co-glycolic acid) (PLGA) nanoparticles, subsequently coated with macrophage-derived cell membranes. Within this framework, PFH serves as the mediator for ultrasonic (US)-irradiation-triggered drug release specifically within tumour microenvironment, while the macrophage-derived cell membrane coating enhances cell adhesion, enables immune evasion, and natural tumour-homing ability. The characterization assays and in vitro evaluations yielded encouraging results, indicating enhanced targeting and release efficiencies. In vivo studies demonstrated marked inhibitory effects on both breast cancer recurrence and pulmonary metastasis. The resulting data indicate that these engineered nanoparticles have notable potential for targeted delivery and controlled release upon US irradiation, thereby offering significant therapeutic efficacy against primary breast cancer, pulmonary metastasis, and recurrent malignancies. Our findings lay the groundwork for a novel clinical approach, representing an intriguing direction for ongoing investigation by oncologists.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causing the coronavirus disease 2019 pandemic (COVID-19) has put millions of people at risk in an increasing number of countries, suggesting a serious threat to global public health. The first identification in late 2019, the strain has undergone several changes that have resulted in several genetically different variations that are cause for concern. By comprising the Delta, Gamma, Beta, and Alpha variations, each of which has shown evidence of increased virulence, transmissibility, or capacity for immune evasion as compared to ancestral strains. Their advancement over ancestral strains in transmission was discovered by genomic surveillance, highlighting the vital necessity for monitoring the evolution of SARS-CoV-2. Remdesivir and other treatments showed promising results in reducing the duration of the disease; however, the development of antivirals to prevent the emergence of new variations is still an important goal. The vaccine also provides hope, although its effectiveness against new genotypes needs to be evaluated. Pakistan is also facing the implications of COVID-19. The months-long closing of colleges and universities affected education as well. As SARS-CoV-2 continues to evolve, creating efficient antiviral therapies and guaranteeing vaccination accessibility continue to be critical concerns.

Itraconazole (ITZ) is a renowned antifungal medication, however its therapeutic efficacy is limited by low solubility and oral bioavailability. The current research work attempted to augment the oral bioavailability of ITZ by incorporating into self-emulsifying micelles (SEMCs). To fabricate the SEMCs, various preparation techniques including physical mixture, melt-emulsification, solvent evaporation and kneading, were opted by using different weight ratio of drug and solubilizers i.e. Gelucire-50/13 or Gelucire-44/14 and characterized both in vitro and in vivo. The prepared SEMCs were found to be in the size range from 63.4 ± 5.2 to 284.2 ± 19.5 nm with surface charges ranging from −16 ± 1.2 to −27 ± 2.0 mV. The drug solubility was improved to a reasonable extent with all investigated formulations, however, SEMCs in group 6 prepared by kneading method (KMG6) using Gelucire-44/14: drug (10:1 presented 87.6 folds’ increase (964.93 ± 2 μg/mL) compared to solubility of crystalline ITZ (11 ± 2 μg/mL) through kneading method. In addition, KMG6 SEMCs shows the fast drug release compared to other SEMCs. Further, KMG6 SEMCs also exhibited 5.12-fold higher relative intestinal serosal fluid absorption compared to crystalline ITZ. The pharmacokinetic parameters such Cmax, AUC and Tmax of KMG6 SEMCs significantly improved compared to crystalline ITZ. In conclusion, the manipulation of ITZ solubility, dissolution rate and absorption using SEMCs is a promising strategy for bioavailability enhancement.

Purpose: A prospective, observational study was done at the country leading tertiary care hospital to evaluate etiologies, clinical features, diagnosis, and prognosis of cerebral venous sinus thrombosis (CVST) in the Pakistani population. Methods: 34 patients with clinical and MRI features suggestive of CVST were evaluated. Modified Rankin Score (mRS) was assessed of all patients at presentation. Results: The mean age of presentation was 30.69 years with female predominance (n = 28). Headache was most common presenting symptoms (97%, n = 33) followed by seizure (59%, n = 20), hemiparesis (56%; n = 19), altered sensorium (47%; n = 16), vomiting (21%; n-7) and cranial nerve involvement (18%; n = 6). 72% of patients (n = 23) had thrombosis of superior sagittal sinus, 53% of patients (n = 17) had thrombosis of the transverse sinus, 25% patients (n = 8) of patients had sigmoid sinus thrombosis, 16 % patients (n = 8) had straight sinus thrombosis. The most common cause for provoked CVST was found to be pregnancy/puerperium in 53% (n = 18 patients), followed by previous CVST/DVT in 12% (n = 4), and then OCP and parainfectious causes which were 3% (n = 1) for each and elevated factor VIII and protein deficiency were found in 7 patients. MRS between 3 and 5 was assessed in most patients on presentation (n = 23). Conclusion: CVST is an under-recognized cause of stroke in the young population, especially in the puerperium period. Clinical presentation is highly variable, and correction with magnetic resonance imaging with venography is the current diagnostic modality of choice. Aggressive management with anticoagulants is safe with excellent clinical outcomes.

Anti N-methyl-D-aspartate (NMDA) receptor encephalitis is new entity discovered over a decade. It is a type of autoimmune encephalitis characterized by a sequential onset of neuropsychiatric symptoms especially in the young population. Early diagnosis and treatment lead to better outcome and may prevent permanent neurological deficit or even death. Most patients respond well to first-line treatment and the resection of tumors associated with the disease. Here we present a case, which based on radiological findings, was diagnosed as cerebral venous sinus thrombosis (CVST), and was started on anticoagulation. Failure to respond to treatment and development of new movement abnormalities warranted for further investigations and he was found to have anti-NMDA receptor antibody positive in cerebrospinal fluid. Due to overlapping symptoms of CVST and encephalitis, high incidence of cerebral venous sinus thrombosis in this part of the world, and radiological findings, was initially thought to have CVST which was also confirmed on brain imaging. Lack of consent by the parents for a lumbar puncture delayed the definitive diagnosis. Patient developed movement disorder suggestive of autoimmune encephalitis, and this time after extensive counselling, when the cerebrospinal fluid was send for work up, it showed a positive anti-NMDA receptor antibody. He was promptly started on plasmapheresis after which patient had dramatic improvement both in movement abnormalities and neuropsychiatric symptoms.

Multisystem involvement has not been uncommon in SARS-CoV-2 infection. There has been reports of devastating neurological complication both during and after the infection. Here we present a rare case of sino-orbital mucormycosis, diagnosis of which was confirmed on histopathology. Our patient presented with headache, 18 days after her recovery from SARS-CoV-2 infection and was extensively worked up for the cause. Initially she was treated as a severe sinusitis but failure to response to antibiotics treatment warranted for further investigations and imaging. Our patient had to undergo right eye enucleation plus debridement under general anesthesia. She is currently on anti-fungal treatment as advised by infectious disease department.

The neurological manifestations of SARS-CoV-2 are wide-ranging from simple headache to severe demyelinating brain disease. This is a review of collected case reports of patients with SARS-CoV-2 with neurological manifestations presenting to the Pakistan Institute of Medical Sciences (PIMS). Neurological manifestations associated with SARS-CoV-2 such as encephalitis, acute cerebrovascular disease, encephalitis with chorea, post-COVID myositis and Guillain-Barré Syndrome (GBS) are of great concern but are often overlooked in the presence of life-threatening abnormal vital signs in severely ill SARS-CoV-2 patients. There is a need to diagnose these manifestations at the earliest opportunity to limit long-term consequences and complications. Much research is needed to explore the role of SARS-CoV-2 in causing these neurological manifestations by isolating it either from the cerebrospinal fluid (CSF) or the brain tissue of the deceased on autopsy. We also recommend exploring the risk factors that lead to the development of these neurological manifestations.

Abstract Background Significance of total ischemic time (TIT) in the context of ST-segment elevation myocardial infarction (STEMI) is still controversial. Therefore, in this study, we have evaluate the association of TIT with immediate outcomes in STEMI patients in whom recommended door to balloon (DTB) time of less than 90 min was achieved. Results A total of 5730 patients were included in this study, out of which 80.9% were male and median age was 55 [61–48] years. The median DTB was observed to be 60 [75–45] min and onset of chest pain to emergency room (ER) arrival time was 180 [300–120] min. Prolonged TIT was associated with poor pre-procedure thrombolysis in myocardial infarction (TIMI) flow grade (p = 0.022), number of diseased vessels (p = 0.002), use of intra-aortic balloon pump (p = 0.003), and in-hospital mortality (p = 0.002). Mortality rate was 4.5%, 5.7%, and 7.8% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. Thirty days’ risk of mortality on TIMI score was 4.97 ± 7.09%, 5.01 ± 6.99%, and 7.12 ± 8.64% for the patients with TIT of ≤ 120 min, 121 to 240 min, and > 240 min, respectively. Conclusions Prolonged total ischemic was associated with higher in-hospital mortality. Therefore, TIT can also be considered in the matrix of focus, along with DTB time and other clinical determinants to improve the survival from STEMI.

The peel from Citrus-sinensis L. is a medicinally significant food waste, and its extract (O-Ext) could be significant against oxidative stresses and skin aging, However, the penetration barriers, instability in formulation, undefined toxicities, and enzymatic activities make the O-Ext difficult to formulate and commercialize. The goal of this study was to evaluate O-Ext against oxidative stress, prepare O-Ext-loaded nano-lipid carriers (O-NLCs), and load them into topical O/W-emulsion (O-NLC-E) to improve O-Ext permeation and its in vivo antiaging effects. TPC, TFC, DPPH activity, and mineral/metal contents of O-Ext were determined via atomic-absorption spectroscopy. For bioactive compounds profiling, GC-MS analysis was carried out. O-NLCs were prepared and tested for physicochemical attributes, while HaCaT and fibroblast cells were used to study permeation and cytotoxicity. The kinetic characteristics of ex vivo permeation through rat skin were established, following the Higuchi model. Following written consent, safety investigations were conducted on human volunteers for three months, where optimized O-NLC-E and B-NLC-E were regularly applied on cheeks. Non-invasive procedures were used to assess the volunteer’s skin erythema, TEWL, sebum level, melanin, hydration, pH, elasticity, and pore sizes after specified intervals. The results demonstrated that applying O-NLC-E formulation to the skin of volunteers directed significant antiaging benefits. The study offers nanotechnology-based sustainability approach against skin ageing.

Abstract The pandemic of severe acute respiratory virus (SARS-CoV-2) is characterized by respiratory symptoms with serious consequences, mainly associated with pneumonia and extreme ARDS. There is a lack of data about pneumothorax associated with COVID-19 infections in current literature. Radiological features in SARS-CoV-2 include subpleural bilateral ground-glass appearance and many areas of irregular consolidation in the lungs. We here present a case of SARS-CoV-2 that was complicated by acute pneumothorax, and despite prompt treatment, that patient could not be saved. A 55-years-old male with no previous lung disease or any other history confirmed to have SARS-CoV-2 pneumonia developed a large pneumothorax on the third day of his presentation and was immediately intubated via a chest tube but could not be saved. SARS-CoV-2 by RT-PCR was positive. The patient expired around 12 h after chest intubation. Recommended treatment could not be started yet as the patient expired before it could be decided.

Abstract Genetic polymorphisms in the MTNR1B gene is associated with type 2 diabetes mellitus (T2DM); however, there is no evidence about its impact on the therapeutic efficacy of nateglinide. This prospective case–control study was designed to investigate the effect of MTNR1B rs10830963 gene variant on the therapeutic efficacy of nateglinide in treating T2DM. We genotyped untreated T2DM patients (N = 200) and healthy controls (N = 200) using the method of the high resolution of melting curve (HRM). Newly diagnosed T2DM patients (n = 60) with CYP2C9*1 and SLCO1B1 521TT genotypes were enrolled and given oral nateglinide (360 mg/d) for 8 weeks. The outcome was measured by collecting the venous blood samples before and at the 8th week of the treatment. The risk G allelic frequency of MTNR1B rs10830963 was higher in T2DM patients than the healthy subjects (P

Breast cancer brain metastases (BCBMs) are one of the most difficult malignancies to treat due to the intracranial location and multifocal growth. Chemotherapy and molecular targeted therapy are extremely ineffective for BCBMs due to the inept brain accumulation because of the formidable blood‒brain barrier (BBB). Accumulation studies prove that low density lipoprotein receptor-related protein 1 (LRP1) is promising target for BBB transcytosis. However, as the primary clearance receptor for amyloid beta and tissue plasminogen activator, LRP1 at abluminal side of BBB can clear LRP1-targeting therapeutics. Matrix metalloproteinase-1 (MMP1) is highly enriched in metastatic niche to promote growth of BCBMs. Herein, it is reported that nanoparticles (NPs-K-s-A) tethered with MMP1-sensitive fusion peptide containing HER2-targeting K and LRP1-targeting angiopep-2 (A), can surmount the BBB and escape LRP1-mediated clearance in metastatic niche. NPs-K-s-A revealed infinitely superior brain accumulation to angiopep-2-decorated NPs-A in BCBMs bearing mice, while comparable brain accumulation in normal mice. The delivered doxorubicin and lapatinib synergistically inhibit BCBMs growth and prolongs survival of mice bearing BCBMs. Due to the efficient BBB penetration, special and remarkable clearance escape, and facilitated therapeutic outcome, the fusion peptide-based drug delivery strategy may serve as a potential approach for clinical management of BCBMs.

The pandemic of severe acute respiratory virus (SARS-CoV-2) is characterized by respiratory symptoms with serious consequences, mainly associated with pneumonia and extreme ARDS. There is a lack of data about specific neurological manifestations of covid-19 infections literature. Epidemiological trials in fewer than 30% of a population reported symptoms of headache and delirium (Helms et al., 2020). Covid-19’s neurotropism is still debatable, uncertain and in the present case study patient with Covid-19 is identified. He suffered with extreme respiratory complications during hospitalization and eventually died.

Background: This study was conducted with the aim of providing a quantitative appraisal of clinical outcomes of trans-radial access for primary percutaneous coronary interventions (PCI) in patients with ST-segment evaluation myocardial infarction (STEMI). Methods: In this study, we compared two propensity-matched cohorts of patients who underwent primary PCI via trans-radial (TRA) and trans-femoral access (TFA) in a 1:1 ratio. The profile of two cohorts was matched for gender, age, and body mass index, diabetes, hypertension, family history, and smoking. The outcomes of primary PCI were compared for the two cohorts which included all-cause in-hospital mortality, heart failure, re-infarction, cardiogenic shock, bleeding, transfusion, cerebrovascular accident, and dialysis. Results: This analysis was performed on a total of 2316 patients with 1158 patients each in the TRA and TFA group. We observed significantly lower rates of mortality, 0.8% (9) vs. 3.5% (41); p

Objective: To compare perioperative use of tranexamic acid with placebo in patients with hip fractures in terms of frequency of deep venous thrombosis. Study Design: Quasi experimental study. Place and Duration of Study: CMH Orthopedics department Rawalpindi, from Apr 2017 to Oct 2017. Methodology: A total of 306 patients presenting with hip fracture, 50 to 90 years of age were included. Patients with Hip fractures presenting with sepsis, hypercoagulable state, pregnancy and breast feeding and contra-indication to tranexamic acid were excluded. The sample size was divided into two equal groups by lottery method, Tranexamic Acid (TXA) and Placebo. The patient was followed till 15th post op day for the purpose of study and at 15th post op day a Doppler ultrasound was performed on both lower limbs and presence or absence of deep venous thrombosis was recorded. Results: The mean age of patients in group A (tranexamic acid group) was 70.80 ± 11.13 years and in group B (placebo group) was 71.50 ± 11.30 years. Out of these 306 patients, 215 (70.26%) were male and 91 (29.74%) were females. Deep venous thrombosis was seen in 31 patients in group A (tranexamic acid group) and 14 patients in group B (placebo group) with p-value of 0.006. Conclusion: Frequency of deep venous thrombosis was observed more in patients receiving perioperative intravenous tranexamic acid as compared to control.

Pakistan has been experiencing a continuous rise in the incidence of Crimean Congo Haemorrhagic Fever (CCHF). Sporadic cases of CCHF are reported from rural areas of Punjab, Azad Jammu Kashmir and Khyber Pakhtunkhwa and neighbouring Afghanistan where cattle herding is common. The objective of this paper was to describe the epidemiology of CCHF. A descriptive study was carried out in the CCHF isolation ward in Islamabad in a tertiary care hospital from February to November 2018. Using a standardised case definition, all patients admitted in the isolation ward with clinical evidence of CCHF were included in the study. After taking the informed consent, data were collected on demographic factors, history of animal contact, tick-bite history, co-morbidity, laboratory results and treatment outcome. Data were analysed as per time, place and person. During the study period, 40 suspected CCHF patients were admitted in the isolation ward, 32 (80%) males were affected. Mean age of the cases was 33.5 years (range 13–70 years). Most affected 17 (42.5%) age group was 20–29 years. Animal contact history was found in Thirty-seven (92.5%) of cases and 28 (70%) with tick bites. Most of the cases, 26 (65%), were reported from July to August. Forty patients in this study were tested by Real Time Polymerase Chain Reaction (PCR), 20 (50%) were positive, out of which 6(30%) expired. Majority of the positive patients were animal handlers by occupation (37.5%). Proper personal protective equipment was available. The reference laboratory facility was not available for immediate investigations was sent to National Institute of Health for confirmation. The overall results show the important risk factors for CCHF a history of tick bites, high-risk occupations and having contact with livestock. Public health measures should focus on preventing tick bites, increasing awareness of CCHF signs and symptoms, timely investigation, and treatment to reduce mortality. Our analyses recommend the government to set up isolation units in all major hospitals, and proper surveillance system.

Background: Covid-19 pandemic has been manifested mainly as respiratory and constitutional symptoms. Though, it may demonstrate the involvement of other systems i.e. cardiovascular system (CVS), central nervous system (CNS) or gastrointestinal system (GI). Discussion: Systemic manifestation of Covid-19 requires further research. Recent surveys revealed a few alarming facts about Covid-19, that, when it hits the brain, can cause some serious complications like; psychosis, stroke and dementia. Case Presentation: Here, the case is about two patients, having PCR confirmed Covid-19 and radiographic evidence of stroke, who eventually died during hospital stay. Data collection was done after informed consent and in retrospective manner.

SARS-CoV-2 infections are transmitted through droplets or through direct contact with secretions from an infected person. The transmission of the virus through tears and other body secretions remains controversial. PCR detection of Covid-19 in the samples/swabs taken from nasopharynx, CSF fluid, and tears, clarifies that the virus may be transmitted through the modes other than aerosol droplets or direct contact. In order to control and prevent this infectious disease, cutting-off the route of transmission will be one of the most important steps. SARS-CoV-2 RNA has been detected in tears and conjunctival samples of patients. The ocular tropism of Covid-19 is still uncertain but contentious.

'Background': The 2019 novel coronavirus (SARS-CoV-2) originated in the central Chinese city, Wuhan, at the end of December 2019. Pakistan reported its first 2 confirmed cases on 26February 2020, linked to a travel history of Iran. This study was conducted to see the trends of COVID-19 infection growth and doubling time in Pakistan, from an early containment state to a much belated exponential rise pattern. 'Method': This study is based on the analysis of the publicly available data on COVID-19 from the Ministry of National Health Services Regulations and Coordination’s COVID-19 dashboard and the publicly available National command and operation centre daily situation reports from 26February - 27July 2020 to show the trends and patterns of COVID-19 among the Pakistani population. 'Results': A total of 275,225 COVID-19 patients have been reported, with 5,865 deaths, 1,229 critically ill, and 242,436 recovered. Sindh has the highest number of confirmed cases (92,279). The majority of affected patients are male (72%). Local transmission cases stand at 97%. The percentage positivity has now declined to 4.8%, reaching a peak value of 25.7% in May. An average of 6.4 daily tests were conducted for each confirmed case, which makes 0.11 daily tests per thousand people. Daily cases surge had a 5.8% increase per day, with a 5-fold increase in infection until mid-June, which has now decreased to 80%. On 13 June 2020, the highest number of cases were reported (6,825 new highest daily deaths were reported on 19 June 2020). The case doubling time was 3 days initially and now stands at 28 days. The current CFR is 2.1%, with 5,865 deaths. 'Conclusion': The lack of effective quarantine facilities and limited testing capacities at the Taftan border crossing resulted in the importation of the virus in the country. Risk mitigation measures that were implemented, such as lockdown by provinces and the Federal government, were eased in mid-May due to the economic impact but was followed by a spike in cases. The cumulative confirmed case count, after showing an exponential growth pattern within two months of the start of the outbreak, is now on the decline. Careful and responsible behaviors from people, preparedness, and planning, including sentinel surveillance at the district level, are required for the sustainability of COVID-19 control.''

Abstract: Background: The 2019 novel coronavirus disease (COVID-19) has spread to more than 213 countries and as of 17th April 2020, 1995,983 confirmed cases and 131,037 deaths have been reported globally. Pakistan being sharing border with China and Iran, having high frequency of travel and trade has been at risk of viral transmission. Methods: We examined current state of COVID-19 epidemic and preparedness in Pakistan using publicly available data and documents on COVID-19 government dashboard. Results: Pakistan reported its first 2 confirmed cases, on 26th February 2020 linked to travel history of Iran. The number of confirmed cases nationwide rose to 7,025 on 17th April 2020 with 135 deaths and 3276 confirmed cases in Punjab,2008 cases in Sindh,993 in Khyber Pathunkhawa,303 in Baluchistan,237 in Gilgit Baltistan,154 in ICT and 46 in Azad Jammu Kashmir. To-date 7000 Pakistani pilgrims have returned from Iran and placed in quarantine in Taftan. Directing of pilgrims back to their cities without testing at the border resulted in introduction of virus in country. Pakistan’s weak healthcare system with 0.6 bed for 1000 people and less than 0.75% of GDP as health spending is doubtful to bear the COVID-19 shock in case of exponential increase in cases. Conclusion: Low literacy rate and general lack of awareness leading to non-seriousness of people towards the adoption of social distancing and hand hygiene. The high population density in major cities of Pakistan can facilitate in the spread of virus. Three-pronged approach of trace, test and treat needs to be aggressively implemented to halt the community transmission leading to exponential increase in cases. Keywords: COVID-19,Preparedness,Three-pronged approach, community transmission.

Pentazocine (PTZ), a narcotic-antagonist analgesic, has been extensively used in the treatment of initial carcinogenic or postoperative pain. Hepatic first-pass metabolism results in low oral bioavailability and high dose wastage. Herein, 10 mg (-)-Pentazocine (HPLC-grade) was incorporated to solid lipid nanoparticles (SLNs) using a double water-oil-water (w/o/w) emulsion by solvent emulsification–evaporation technique, followed by high shear homogenization to augment its oral bioavailability, considering the lymphatic uptake. The resulting SLNs were characterized for zeta potential (ZP), particle size (PS), and polydispersity index (PDI) using a zetasizer. The entrapment efficiency (EE) and loading capacity (LC) were calculated. Chemical interactions, through the identification of active functional groups, were assessed by Fourier-transformed infrared (FTIR) spectroscopy. The nature (crystallinity) of the SLNs was determined by X-ray diffractometry (XRD). The surface morphology was depicted by transmission electron microscopy (TEM). In vitro (in Caco-2 cells) and in vivo (in male Wistar rats) investigations were carried out to evaluate the PTZ release behavior and stability, as well as the cellular permeation, cytotoxicity, systemic pharmacokinetics, antinociceptive, anti-inflammatory, and antioxidative activities of PTZ-loaded SLNs, mainly compared to free PTZ (marketed conventional dosage form). The optimized PTZ-loaded SLN2 showed significantly higher in vitro cellular permeation and negligible cytotoxicity. The in vivo bioavailability and pharmacokinetics parameters (t1/2, Cmax) of the PTZ-loaded SLNs were also significantly improved, and the nociception and inflammation, following carrageenan-induced inflammatory pain, were markedly reduced. Concordantly, PTZ-loaded SLNs showed drastic reduction in the oxidative stress (e.g., malonaldehyde (MDA)) and proinflammatory cytokines (e.g., Interleukin (IL)-1β, -6, and TNF-α). The histological features of the paw tissue following, carrageenan-induced inflammation, were significantly improved. Taken together, the results demonstrated that PTZ-loaded SLNs can improve the bioavailability of PTZ by bypassing the hepatic metabolism via the lymphatic uptake, for controlled and sustained drug delivery.

'Background:' Influenza is a common respiratory disease in Pakistan. However, the absence of a robust surveillance system makes it difficult to estimate the burden of disease. 'Purpose:' We conducted this study to identify key strengths and weaknesses of the laboratory-based influenza surveillance system in Pakistan and to make recommendations for improvement. 'Methods:' We conducted an evaluative descriptive study of the national laboratory-based influenza surveillance system from April to July 2017. We conducted this assessment using the updated guidelines for evaluating public health surveillance systems issued by CDC in 2011. 'Findings: 'The system was found to be simple and easy to operate, but with little flexibility to integrate with other pathogens and diseases. Data quality was good, given that 80% of observed forms were completed. Timeliness was good, as it takes only 24-48 hours from sample collection to report a submission to the central level. Acceptability was good, since both private and public sector hospitals and labs are involved. Sensitivity was 62% and positive predictive value (PPV) was 37.2%. The representativeness of lab based influenza surveillance system was poor, since it is a sentinel surveillance system with specific, strategically placed reporting sites. 'Conclusions:' The system meets its objectives. Sustainability and stability of the system needs to be improved by allocation of public funds. Coverage of the system should be expanded to improve representativeness. Regular capacity building with staff at reporting sites will ensure continued quality of reporting.

Diabetic wound infections caused by conventional antibiotic-resistant Staphylococcus aureus strains are fast emerging, leading to life-threatening situations (e.g., high costs, morbidity, and mortality) associated with delayed healing and chronic inflammation. Electrospinning is one of the most widely used techniques for the fabrication of nanofibers (NFs), induced by a high voltage applied to a drug-loaded polymer solution. Particular attention is given to electrospun NFs for pharmaceutical applications (e.g., original drug delivery systems) and tissue regeneration (e.g., as tissue scaffolds). However, there is a paucity of reports related to their application in diabetic wound infections. Therefore, we prepared eco-friendly, biodegradable, low-immunogenic, and biocompatible gelatin (GEL)/polyvinyl alcohol (PVA) electrospun NFs (BNFs), in which we loaded the broad-spectrum antibiotic cephradine (Ceph). The resulting drug-loaded NFs (LNFs) were characterized physically using ultraviolet-visible (UV-Vis) spectrophotometry (for drug loading capacity (LC), drug encapsulation efficiency (EE), and drug release kinetics determination), thermogravimetric analysis (TGA) (for thermostability evaluation), scanning electron microscopy (SEM) (for surface morphology analysis), and Fourier-transform infrared spectroscopy (FTIR) (for functional group identification). LNFs were further characterized biologically by in-vitro assessment of their potency against S. aureus clinical strains (N = 16) using the Kirby–Bauer test and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, by ex-vivo assessment to evaluate their cytotoxicity against primary human epidermal keratinocytes using MTT assay, and by in-vivo assessment to estimate their diabetic chronic wound-healing efficiency using NcZ10 diabetic/obese mice (N = 18). Thin and uniform NFs with a smooth surface and standard size (S. aureus-induced chronic wounds in diabetic subjects.

Multiple high-performance liquid chromatographic (HPLC) approaches have been briefly defined for the assessment of zolmitriptan (ZMT). These methods are either cumbersome or require a plentiful volume of organic solvents, thus offering extortionate procedures. The objective of this study was to establish and validate a new rapid, eco-friendly and cost-effective HPLC method for the analysis of ZMT. The calibration curve for ZMT was established using simulated salivary fluid (SSF) and rat plasma for in-vitro and in-vivo analysis, respectively. Chromatogram separation was performed using a CST column (250mm x 4.6mm, 5µm) as a stationary phase and maintained at a temperature of 40°C. The methods were authenticated for linearity, system suitability, accuracy, precision, reproducibility, limit of detection (LOD) and limit of quantification (LOQ). The results of the validation variables and stability studies indicated that the methods were established in accordance with the guidelines of ICH and the USFDA. The established technique was time-saving, precise, eco- friendly and economical compared with the reported technique. In addition, the developed method was sufficiently repeatable for in vitro and in vivo analysis of ZMT. [ABSTRACT FROM AUTHOR]