Biomolecular Screening of Pimpinella anisum L. for Antioxidant and Anticholinesterase Activity in Mice Brain.

Hundreds of the plants have been explored and evaluated for antioxidant and anti-amnesic activities, so far. This study was designed to report the biomolecules of Pimpinella anisum L. for the said activities. The aqueous extract of dried P. anisum seeds was fractionated via column chromatography and the fractions so obtained were assessed for the inhibition of acetylcholinesterase (AChE) via in vitro analysis. The fraction which best inhibited AChE was so named as the P. anisum active fraction (P.aAF). The P.aAF was then chemically analyzed via GCMS, which indicated that oxadiazole compounds were present in it. The P.aAF was then administered to albino mice to conduct the in vivo (behavioral and biochemical) studies. The results of the behavioral studies indicated the significant (p < 0.001) increase in inflexion ratio, by the number of hole-pokings through holes and time spent in a dark area by P.aAF treated mice. Biochemical studies demonstrated that the oxadiazole present in P.aAF on one hand presented a noteworthy reduction in MDA and the AChE level and on the other hand promoted the levels of CAT, SOD and GSH in mice brain. The LD50 for P.aAF was calculated as 95 mg/Kg/p.o. The findings thus supported that the antioxidant and anticholinesterase activities of P. anisum are due to its oxadiazole compounds.

Fabrication and Evaluation of Anticancer Potential of Eugenol Incorporated Chitosan-Silver Nanocomposites: In Vitro, In Vivo, and In Silico Studies.

The expanding global cancer burden necessitates a comprehensive strategy to promote possible therapeutic interventions. Nanomedicine is a cutting-edge approach for treating cancer with minimal adverse effects. In the present study, chitosan-silver nanoparticles (ChAgNPs) containing Eugenol (EGN) were synthesized and evaluated for their anticancer activity against breast cancer cells (MCF-7). The physical, pharmacological, and molecular docking studies were used to characterize these nanoparticles. EGN had been effectively entrapped into hybrid NPs (84 ± 7%). The EGN-ChAgNPs had a diameter of 128 ± 14 nm, a PDI of 0.472 ± 0.118, and a zeta potential of 30.58 ± 6.92 mV. Anticancer activity was measured in vitro using an SRB assay, and the findings revealed that EGN-ChAgNPs demonstrated stronger anticancer activity against MCF-7 cells (IC50 = 14.87 ± 5.34 µg/ml) than pure EGN (30.72 ± 4.91 µg/ml). To support initial cytotoxicity findings, advanced procedures such as cell cycle analysis and genotoxicity were performed. Tumor weight reduction and survival rate were determined using different groups of mice. Both survival rates and tumor weight reduction were higher in the EGN-ChAgNPs (12.5 mg/kg) treated group than in the pure EGN treated group. Based on protein-ligand interactions, it might be proposed that eugenol had a favorable interaction with Aurora Kinase A. It was observed that C9 had the highest HYDE score of any sample, measuring at -6.8 kJ/mol. These results, in conjunction with physical and pharmacological evaluations, implies that EGN-ChAgNPs may be a suitable drug delivery method for treating breast cancer in a safe and efficient way.

Diagnosis of Acute Dengue Virus Infection Using Enzyme-Linked Immunosorbent Assay and Real-Time PCR.

Dengue fever is a viral infection caused by the dengue virus and is a growing concern for public health worldwide, particularly in tropical and subtropical regions. This study aimed to assess the diagnostic accuracy of a commercially available NS1 ELISA kit for dengue fever in Pakistan using multiplex qRT-PCR as the gold standard. The study recruited 1236 suspected cases of dengue fever admitted to public sector hospitals in Lahore, Pakistan. Of the suspected cases, 610 (49.3%) were confirmed positive for DENV infection through qRT-PCR, with all four serotypes detected. DENV-2 was the most prevalent serotype, detected in 95.7% of cases. The NS1 ELISA kit detected 71.1% of the positive cases. However, the diagnostic accuracy of the NS1 ELISA kit was found to be only 64.89%. Of the 610 confirmed cases, 68% were male and 32% were female, with a median age of 30 years. Dengue fever was diagnosed in 91.8% of cases, while 8.2% were diagnosed with dengue hemorrhagic fever (DHF). DHF patients had a higher prevalence of abdominal pain, hemorrhagic manifestations, and thrombocytopenia. The cocirculation of all four DENV serotypes in Lahore is concerning and could lead to more severe forms of the disease, such as DHF or dengue shock syndrome, in the future. The study highlights the low diagnostic accuracy of commercially available NS1 ELISA kits and emphasizes the importance of using molecular methods to confirm acute dengue infections. Given the increasing prevalence of dengue fever in developing countries like Pakistan, more accurate and reliable diagnostic tools are needed for effective disease management and control.

An experience of mass administration of fractional dose inactivated polio vaccine through intradermal needle-free injectors in Karachi, Sindh, Pakistan.

BACKGROUND: Inactivated Polio Vaccine (IPV) campaign was conducted in February 2019 in Karachi where needle-free injectors were introduced for the administration of the fractional dose of IPV (fIPV) on a large scale. This study aimed to determine the impact of needle-free injectors on vaccination coverage. METHODS: In four towns of Karachi, fIPV was given using needle-free injectors "PharmaJet Tropis ID". Whereas, in six towns full dose of IPV was administered to children of 4-59 months of age. Cluster surveys through rapid convenience assessment method were conducted after the completion of vaccination activity. RESULTS: A total of 33,815 households' data was analyzed. Among these, 27,650 (82.8%) children were vaccinated. In fIPV areas, 85.3% of children were vaccinated compared to 79.5% in full dose IPV areas. A comparison of reasons for unvaccinated showed that 1.6% of parents do not give importance to vaccination in fIPV areas compared to 4.2% in full IPV areas (p-value < 0.0001). More children were not vaccinated due to fear of injection 1.8% in full IPV areas compared to 0.7% in fIPV areas (p-value < 0.0001). The source of campaign information shows that more frequent mobile miking 3.1% was observed in fIPV areas compared to 0.4% in full IPV areas (p-value < 0.0001). CONCLUSIONS: Our analysis supports the fractional dose of IPV in mass campaigns to achieve good vaccination coverage especially using needle-free injectors "PharmaJet Tropis ID" and vigorous social mobilization activities are expedient in accomplishing high coverage.

Biochemical and Immunological implications of Lutein and Zeaxanthin.

Throughout history, nature has been acknowledged for being a primordial source of various bioactive molecules in which human macular carotenoids are gaining significant attention. Among 750 natural carotenoids, lutein, zeaxanthin and their oxidative metabolites are selectively accumulated in the macular region of living beings. Due to their vast applications in food, feed, pharmaceutical and nutraceuticals industries, the global market of lutein and zeaxanthin is continuously expanding but chemical synthesis, extraction and purification of these compounds from their natural repertoire e.g., plants, is somewhat costly and technically challenging. In this regard microbial as well as microalgal carotenoids are considered as an attractive alternative to aforementioned challenges. Through the techniques of genetic engineering and gene-editing tools like CRISPR/Cas9, the overproduction of lutein and zeaxanthin in microorganisms can be achieved but the commercial scale applications of such procedures needs to be done. Moreover, these carotenoids are highly unstable and susceptible to thermal and oxidative degradation. Therefore, esterification of these xanthophylls and microencapsulation with appropriate wall materials can increase their shelf-life and enhance their application in food industry. With their potent antioxidant activities, these carotenoids are emerging as molecules of vital importance in chronic degenerative, malignancies and antiviral diseases. Therefore, more research needs to be done to further expand the applications of lutein and zeaxanthin.

Preparation, Characterization, and Pharmacological Investigation of Withaferin-A Loaded Nanosponges for Cancer Therapy; In Vitro, In Vivo and Molecular Docking Studies.

The rapidly growing global burden of cancer poses a major challenge to public health and demands a robust approach to access promising anticancer therapeutics. In parallel, nanotechnology approaches with various pharmacological properties offer efficacious clinical outcomes. The use of new artificial variants of nanosponges (NS) as a transporter of chemotherapeutic drugs to target cells has emerged as a very promising tool. Therefore, in this research, ethylcellulose (EC) NS were prepared using the ultrasonication assisted-emulsion solvent evaporation technique. Withaferin-A (WFA), an active ingredient in Withania somnifera, has been implanted into the nanospongic framework with enhanced anticancer properties. Inside the polymeric structure, WFA was efficiently entrapped (85 ± 11%). The drug (WFA) was found to be stable within polymeric nanosponges, as demonstrated by Fourier transform infrared (FTIR) spectroscopy and differential scanning calorimetry (DSC) studies. The WFA-NS had a diameter of 117 ± 4 nm and zeta potential of -39.02 ± 5.71 mV with a polydispersity index (PDI) of 0.419 ± 0.073. In addition, scanning electron microscopy (SEM) revealed the porous surface texture of WFA-NS. In vitro anticancer activity (SRB assay) results showed that WFA-NS exhibited almost twice the anticancer efficacy against MCF-7 cells (IC50 = 1.57 ± 0.091 µM), as quantified by flow cytometry and comet tests. Moreover, fluorescence microscopy with DAPI staining and analysis of DNA fragmentation revealed apoptosis as a mechanism of cancer cell death. The anticancer activity of WFA-NS was further determined in vivo and results were compared to cisplatin. The anticancer activity of WFA-NS was further investigated in vivo, and the data were consistent to those obtained with cisplatin. At Day 10, WFA-NS (10 mg/kg) significantly reduced tumour volume to 72 ± 6%, which was comparable to cisplatin (10 mg/kg), which reduced tumour volume to 78 ± 8%. Finally, the outcomes of molecular modeling (in silico) also suggested that WFA established a stable connection with nanosponges, generating persistent hydrophobic contacts (polar and nonpolar) and helping with the attractive delayed-release features of the formulation. Collectively, all the findings support the use of WFA in nanosponges as a prototype for cancer treatment, and opened up new avenues for increasing the efficacy of natural product-derived medications.

Antimicrobial resistance: more than 70 years of war between humans and bacteria.

Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).

Prognostic factors in patients with salivary gland malignancy: a retrospective cohort study.

Our objective was to determine the factors affecting the prognosis in patients with major salivary gland malignancy presenting to Aga Khan University Hospital in Karachi. Retrospective cohort study was carried out at our center on patients diagnosed and treated for salivary gland cancers. Presentation and treatment offered was reviewed from medical charts. Telephonic interviews were conducted to assess the survival of patients who were lost to follow-up. Log rank test was used to compare the mean survival times. A total of 36 patients were included in the study. The mean age was 45.1 +/- 14.6 years. Majority were male 21 (58.3%). The most common malignancy was mucoepidermoid carcinoma (36.1%) followed by adenoid cystic carcinoma (22.2%). Node positivity, grade of tumor, radiotherapy and chemotherapy were a significant indication of survival times on log rank test.

Critical Thinking: Perception and disposition of students in a Medical College of Pakistan.

OBJECTIVE: To determine the perception and disposition of medical students towards critical thinking. METHODS: The cross-sectional study was carried out from July 1, 2015, to March 30, 2016, at Gujranwala Medical College, Gujranwala, Pakistan, and comprised undergraduate medical students. Student's perception about critical thinking was assessed through a self-administered questionnaire and the standard California Critical Thinking Disposition Inventory. Data was analysed using SPSS 21. RESULTS: Of the 228 students, 191(84%) were females and 37(16%) were males. Overall mean age was 21.02±1.56 years, and 142(62%) were in the clinical years of their studies. Mean inventory score was 273.3±20. Besides, 157(69%) students perceived critical thinking as a positive thought process, while 52(22.8%) had no idea about it, and 19(8.3%) took critical thinking as a negative process. CONCLUSIONS: Most medical students were found to have a positive perception but they were not disposed towards critical thinking.

Hepatoprotective and Renoprotective Properties of Lovastatin-Loaded Ginger and Garlic Oil Nanoemulsomes: Insights into Serum Biological Parameters.

Background and Objectives: Dyslipidemia is gaining much attention among healthcare professionals because of its high association with the malfunctioning of a number of normal physiological and metabolic processes in the body. Obesity is directly interconnected with dyslipidemia and is said to be a denouement of hyperlipidemia and, if left untreated, may lead to intense damage to organs that are directly involved in fat metabolism. The objective of this study was to investigate the synergistic antiobesity and anti-hyperlipidemic activities along with hepato- and renoprotective potential of nanoemulsomes (NES) of lovastatin (LTN)-loaded ginger (GR) and garlic (GL) oils. Materials and Methods: LTN nanoemulsomes co-encapsulated with GR oil and GL oil were prepared by a thin hydration technique. Eight-week-old male Wistar rats weighing 200-250 g were induced with hyperlipidemia via a high-fat diet (HFD) comprising 40% beef tallow. Body weight, serum biochemical lipid parameters, and those for liver and kidney functions, serum TC, LDL-C, vLDL-C, HDL-C, TG, atherogenic index (AI), ALT, AFT, ALP, γ-GT, total protein (TP), serum albumin and globulin ratio (A/G), serum creatinine, blood urea nitrogen (BUN) and blood urea, and histopathology of hematoxylin and eosin (H&E) stained liver and kidney sections of all aforementioned groups were examined in the treated animals. Results: Nanoemulsomes of LTN-loaded GR and GL oils provided synergistic effects with LTN, exerted better ameliorative actions in reducing serum TC, LDL-C, vLDL-C, triglycerides, and AI, and improved serum HDL-C levels. Serum ALT, AST, ALP, and γ-GT levels were in the normal range for nanoemulsome groups. H&E stained liver and kidney sections of these animals confirmed better hepatoprotective and renoprotective effects than LTN alone. Serum biochemical parameters for renal functions also claimed to be in the moderate range for nanoemulsome-treated groups. Conclusion: This study demonstrated that nanoemulsomes of LTN-loaded GR and GL oils synergistically provided better antihyperlipidemic, hepatoprotective, and renoprotective effects as compared to LTN alone.

Clove oil based co-surfactant free microemulsion of flurbiprofen: Improved solubility with ameliorated drug-induced gastritis.

Flurbiprofen, an NSAID, is a water insoluble drug that is also notorious for gastric irritation and inflammation. This study was aimed at using a natural gastrprotective oil as the internal phase to develop flurbiprofen micro emulsion (ME) to improve it solubility and ameliorate its gastric side effects. Upon screening of ME components for drug solubility, clove oil, tween 80 and transcutol were identified as the oil, surfactant and co surfactant, respectively, with higher flurbiprofen solubility. Pseudo-ternary phase diagrams revealed that the ME made with surfactant only and without co-surfactant displayed the similar ME region as made with the mixture of surfactant and co-surfactant. Furthermore, drug loaded oil was also used to draw pseudo-ternary phase diagram and a very little decrease in the ME region was observed. Therefore, co-surfactant free flurbiprofen loaded ME was developed to avoid side effects associated with the use of excessive surfactant quantities. ME were found to possess size in the range of 11-41 nm with PDI <0.5 and a slightly negative charge. Conductivity, pH and refractive indices of the selected MEs were well in the range. Drug release studies indicated maximum drug release from MEs within 5 min. Analysis of the gastric mucosa of rats after oral administration of drug solution and drug loaded ME confirmed that clove oil based ME provided significant protection against the NSAIDs induced gastric damage.

Cholinesterases inhibition and molecular modeling studies of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones.

Super-activation of cholinesterases (acetylcholinesterase and butyrylcholinesterase) are linked to various neurological problems most precisely Alzheimer's disease (AD), which leads to senile dementia. Therefore, cholinesterases (AChE & BChE) inhibition are considered as a promising strategy for the treatment of Alzheimer's disease. FDA approved drugs for the treatment of AD, belong to a group of cholinesterase inhibitors. However, none of them is able to combat or completely abrogate the disease progression. Herein, we report a series of newly synthesized chalcone derivatives with anti-AD potential. For this purpose, a series of piperidyl-thienyl and 2-pyrazoline derivatives of chalcones were tested for their cholinesterases (AChE & BChE) inhibitory activity. All compounds were found as selective inhibitor of AChE. In piperidyl chalcones derivatives compound 1e having IC50 of 0.16 ± 0.008 µM and 2m in 2-pyrazoline chalcones with IC50 of 0.13 ± 0.006 µM, were found to be the most potent inhibitors of AChE, exhibiting ≈142 and ≈ 173-fold greater inhibitory potential compared to the reference inhibitor i.e., Neostigmine (IC50 ± SEM = 22.2 ± 3.2 µM). Molecular docking studies of most potent inhibitors were carried out to investigate the binding interactions inside the active site. Molecular docking study revealed that potent compounds and co-crystalized ligand had same binding orientation within the active site of target enzyme. Most of these compounds are selective inhibitors of AChE with a potential use against progressive neurodegenerative disorder and age related problems.

Hydrogen functionalization induced two-dimensional ferromagnetic semiconductor in Mn di-halide systems.

We explored the electronic and magnetic properties of two-dimensional manganese di-halides (MnY2, Y = I, Br, Cl) and hydrogenated systems (MnHY2). The pristine MnY2 monolayers had a very weak magnetic exchange interaction and we found degenerated magnetic states between ferromagnetic and antiferromagnetic states although the Mn had a high magnetic moment of 5 µB with a finite band gap. However, we found that the electronic band structure and magnetic properties could be significantly altered by functionalization with hydrogen atoms because the degeneracy in the pristine MnY2 structure was broken and the FM ground state was obtained in all MnHY2 systems. We obtained a negative spin polarization in the H atom and the magnetic moment of the Mn atom decreased from 5 µB to 4 µB. However, this negative polarization played a pivotal role in inducing a FM ground state in the MnHY2 systems. Furthermore, the asymmetric spin dependent bang gap in MnHY2 was also greatly enhanced due to this hydrogenation as compared with that in the pristine MnY2 systems. This finding suggests that the hydrogenated MnHY2 can be used as a potential ferromagnetic semiconductor for spintronics.

Cranioplasty after Craniectomy in a Pediatric Population: Single-Center Experience from a Developing Country.

Cranioplasty is a frequently performed procedure in neurosurgery. The pediatric population for this procedure is distinct from the adult one because of the growing skulls and thinner bones of the calvarium. A paucity of data on the outcomes of this procedure in the pediatric population has been identified repeatedly. We conducted a retrospective cohort study to investigate the outcomes in a pediatric population that underwent cranioplasty after craniectomy at our institute in a developing-world country. Our cohort showed no association of complication rate or cosmetic outcomes with the timing of cranioplasty, area of skull defect, type of implant used, or method of storage.

Role of customised negative-pressure wound therapy in the integration of split-thickness skin grafts: A randomised control study.

BACKGROUND: Split-thickness skin grafting (STSG) is a time-tested technique in wound cover, but many factors lead to suboptimal graft take. Role of custom-made negative-pressure wound therapy (NPWT) is compared with conventional dress in the integration of STSG and its cost is compared with widely used commercially available NPWT. MATERIALS AND METHODS: This is a parallel group randomised control study. Block randomisation of 100 patients into one of the two groups (NPWT vs. non-NPWT; 50 patients each) was done. Graft take/loss, length of hospital stay post-grafting, need for regrafting and cost of custom-made negative pressure wound therapy (NPWT) dressings as compared to widely used commercially available NPWT were assessed. RESULTS: Mean graft take in the NPWT group was 99.74% ± 0.73% compared to 88.52% ± 9.47% in the non-NPWT group (P = 0.004). None of the patients in the NPWT group required second coverage procedure as opposed to six cases in the non-NPWT group (P = 0.035). All the patients in the NPWT group were discharged within 4-9 days from the day of grafting. No major complication was encountered with the use of custom-made NPWT. Custom-made NPWT dressings were found to be 22 times cheaper than the widely used commercially available NPWT. CONCLUSIONS: Custom-made NPWT is a safe, simple and effective technique in the integration of STSG as compared to the conventional dressings. We have been able to reduce the financial burden on the patients as well as the hospital significantly while achieving results at par with other studies which have used commercially available NPWT.

Molecular docking and antiviral activity of N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides.

Two series of fifteen N-substituted benzyl/phenyl-2-(3,4-dimethyl-5,5-dioxidopyrazolo[4,3-c][1,2]benzothiazin-2(4H)-yl)acetamides were screened for anti-HIV-1 activity and cytotoxicity. The compounds 6a, 6d, 6e, 6g and 6i from the series 6a-i of benzylamides and 7a, 7b, 7c, 7d and 7e from the series 7a-f of anilides were identified as effective anti-HIV-1 agents with EC50 values <20µM. Among these compounds that displayed anti-HIV-1 activity, 6a, 6e, 6g and 6i showed no toxicity in human PBM, CEM and Vero cells, with the exception of 6a which displayed toxicity in Vero cells. Molecular docking of these compounds provided insight into the molecular mechanism and it was found that 6e, 6g and 6i bound deeply in the NNRTI binding pocket of the HIV-1 reverse transcriptase, using RT-bound nevirapine X-ray data and molecular docking for validation, showing the potential of these new structures as inhibitors of this viral enzyme.

Genome-wide identification and role of HSFs in antioxidant response of hot water treated zucchini fruit during cold storage.

Zucchini squashes are cold-sensitive and vulnerable to chilling injury (CI) resulting from reactive oxygen species (ROS) and hot water (HW) immersing effectively reduce CI symptoms during cold storage. However, mechanism involved in reduced ROS due to HW treatment has not been characterized well. In this study, tender green zucchini fruit were treated with HW for 15 min at 45 ± 1 °C and stored for 15 d at 4 ± 1 °C and above 90 % relative humidity. Results showed substantial reduction in CI index, electrolyte leakage, malonaldehyde (MDA) contents and ROS accumulation along with increased activity of ROS-scavenging enzymes due to HW treatment. To gain insight into the molecular mechanism involved in antioxidant defense system, transcriptomic analysis revealed that heat shock factors (HSF) accumulated due to HW treatment regulated the ROS pathway during cold stress. CpHSFA4a was one of the highly expressed transcription factors (TF) due to HW treatment that regulated the transcription of ROS enzymes related genes. CpHSFA4a bind actively with heat shock element (HSE) in promoter regions of CpSOD, CpCAT, CpAPX1, CpAPX2, and CpAPX3, activated and increased the expression of these genes. In conclusion, HW treatment alleviated the CI by maintaining ROS homeostasis through CpHSFA4a mediated ROS pathway in zucchini squashes during cold storage.

Exploring the Indications, Levels, and Outcomes of Lower Extremity Amputation at a Tertiary Care Hospital in Pakistan.

BACKGROUND: Lower extremity amputation (LEA) is a surgical procedure performed to remove either a part or the entire lower limb due to medical conditions such as trauma, infection, peripheral vascular disease, or malignancy. The procedure is becoming increasingly common in Pakistan, with a bulk of patients presenting from rural areas in tertiary care centers. Understanding the indications, levels, and outcomes of LEA is essential for improving patient care and adopting preventive strategies, especially in developing countries. METHODOLOGY: This study was conducted at Dow University Hospital in Karachi, Pakistan. Retrospective data of 384 patients who underwent non-traumatic lower extremity amputations between January 2016 and December 2020 was collected to include relevant history and characteristics, amputation indication and level, type of anesthesia used, and outcome within hospital stay. The data was analyzed using descriptive statistics. RESULTS: The data is composed of a wide age range (18 to 91 years) of patients, including a male majority (76.3%, n = 293). The employment status of the patients was taken into consideration, with a reported high number of unemployed individuals (60.4%, n = 232). Diabetes mellitus (84.4%, n = 324) was a commonly reported past medical condition, followed by hypertension (4.4%, n = 17). Indications for amputation exceedingly recorded were diabetic foot ulcers (84.4%, n = 324), followed by infections (9.4%, n = 36) and peripheral arterial disease (3.6%, n = 14). The anesthetic approach that was observed most in these patients was regional anesthesia (74.7%, n = 287). Right-sided amputations (52.9%, n = 203) were dominant, with below-knee amputations leading by the level of amputation performed (42.5%, n = 163). Many patients delayed seeking treatment (71.6%, n = 275) and indicated denial of severity (18%, n = 69) as a reason for the delay. Regarding outcome, many patients were successfully discharged following treatment (85.9%, n = 330). CONCLUSION: Overall, LEAs are being frequently performed in developing countries, such as Pakistan, especially with a large population living with diabetes mellitus. The implications of this disease are reflected in this study population, with the majority of patients reporting delays in treatment due to reasons such as the unknown severity of the disease or financial burdens. The challenges faced by these individuals, especially in this country, can be tackled with widespread affordability and availability of care and education on early management.

Crack Surface Analysis of Elastomers Using Transfer Learning.

Cracks that form during fatigue offer critical information regarding the fracture process of the associated material, such as the crack speed, energy dissipation, and material stiffness. Characterization of the surfaces formed after these cracks have propagated through the material can provide important information complementary to other in-depth analyses. However, because of the complex nature of these cracks, their characterization is difficult, and most of the established characterization techniques are inadequate. Recently, Machine Learning techniques are being applied to image-based material science problems in predicting structure-property relations. Convolutional neural networks (CNNs) have proven their capacity on modeling complex and diverse images. The downside of CNNs for supervised learning is that that they require large amounts of training data. One work-around is using a pre-trained model, i.e., transfer learning (TL). However, TL models cannot be used directly without modification. In this paper, to use TL for crack surface feature-property mapping, we propose to prune the pre-trained model to retain the weights of the first several convolutional layers. Those layers are then used to extract relevant underlying features from the microstructural images. Next, principal component analysis (PCA) is used to further reduce the feature dimension. Finally, the extracted crack features together with the temperature effect are correlated with the properties of interest using regression models. The proposed approach is first tested on artificial microstructures created by spectral density function reconstruction. It is then applied to experimental data of silicone rubbers. With the experimental data, two analyses are performed: (i) analysis of the correlation of the crack surface feature and material property and (ii) predictive model for property estimation, whereby the experiments can be potentially replaced altogether.

Assessment of Primary Care Physicians' Expertise of Common Dermatological Conditions in the Jouf Region, Saudi Arabia: A Mixed Methods Study.

Primary care physicians (PCPs) are the first line of defense for the management of common dermatological conditions (DCs). This study aimed to assess how dermatological diseases are identified, managed, and referred to in primary healthcare centers (PHCs). This was a mixed methods study comprising a cross-sectional survey and semi-structured interviews recruited through PHCs across the Jouf region of Saudi Arabia. Sixty-one PCPs completed the data, and eight participants were interviewed. A survey based on a sample of 22 photographs of common DCs in the Kingdom was administered to the participants to answer questions about the correct diagnosis, appropriate management, referral strategy, and encounter rate. In our sampled population, the mean overall knowledge level on a scale of 10 was 7.08 (±1.3). Among participants that had good to acceptable scores, 51 (83.6%) were in the overall knowledge parameter, 46 (75.4%) in the diagnosis parameter, and 49 (80.3%) in the management parameter. PCPs with five years or more of experience were found to have significantly higher overall knowledge and management scores. Most of our PCPs demonstrated sufficient knowledge of common DCs and had good to acceptable scores in all parameters. However, educational and regulatory aspects of PCPs' clinical management were identified. Focused training, provision of workshops, and improving medical school curricula regarding common DCs are recommended.