Domestic Cylinder Blasts: A Neglected Torpedo.

High-pressure cylinders are used to store liquefied petroleum gas (LPG). An instant and swift explosion of these cylinders can result in serious burn injuries. This current research was conducted to study the epidemiological characteristics of LPG-related burns to highlight a major public health issue. Analysis was conducted on patients with LPG-related burns over a span of 10 years admitted to our center between January 2011 and December 2020. The data recorded included demographic features, site of burn, %TBSA, associated injuries, and outcomes. The variable data were documented for every patient in a Microsoft Excel file and analyzed by IBM SPSS version 25.0. Over the span of 10 years, 678 patients were affected by LPG-related accidents. The peak incidence was seen in 2019 when there was a surge to 18.03%. The patient's age ranged from 1 to 79 years, with a median of 40.86 ± 15.27 years. Of the 678 patients, 52.50% were males and 47.50% were females. The majority (57.96%) of patients had a total BSA of >60% and 86.72% were diagnosed with inhalation injury. The majority of burns (84.66%) occurred at home. The mean hospital stay was 24.5 days. The total mortality rate was 59.58%. This study concludes that LPG cylinder blast is a preventable cause that can be minimized by making people aware of its safe use and by arranging awareness programs at every national level.

Plasma Levels of Interleukin-6 and -18 Significantly Increase in Patients with Acute Coronary Syndrome.

Objectives: Inflammatory pathways play a significant role in atherosclerosis that leads to acute coronary syndrome (ACS). The initial stages of atherosclerosis are often asymptomatic; when atherosclerotic plaques become unstable it leads to ACS. Therefore, early detection, diagnosis, and treatment of atherosclerosis must be sought. These circumstances underpin the need for diagnostic values of inflammatory markers, warranting their routine clinical application to develop anti-atherosclerotic therapeutic approaches. The aim of this case-control observational study was to evaluate the plasma levels of interleukin (IL)-6, IL-18, IL-1ß, and IL-10. Methods: The research was conducted at Hasan Sadikin Hospital from September to December 2021. Patients were recruited based on the typical clinical history of ACS (non-ST-elevation myocardial infarction, ST-elevation myocardial infarction, and unstable angina) and electrocardiographic and cardiac enzyme data. Healthy subjects having no more than one cardiovascular disease risk factor at admission were included. A total of 43 subjects were included in the study, of which 23 subjects were patients diagnosed with ACS and 20 were healthy controls. Results: The results showed that the mean plasma levels of IL-6 (298.6±432.9 pg/mL) in ACS patients were significantly higher than the mean concentration of IL-6 (33.7±96.6 pg/mL) in the control group (p < 0.05). Similarly, the mean plasma level of IL-18 (181.4±81.4 pg/mL) in ACS patients was significantly higher compared to the mean concentration (125.0±29.8 pg/mL) in the control group (p < 0.05), suggesting that both IL-6 and IL-18 were associated with ACS. However, there is no statistically significant difference between IL-1ß and IL-10 levels. A Pearson's correlation analysis showed that a positive correlation exists between IL-6 and IL-18. Conclusions: Both IL-6 and IL-18 are associated with ACS.

Automatically Diagnosing Skin Cancers From Multimodality Images Using Two-Stage Genetic Programming.

Developing a computer-aided diagnostic system for detecting various skin malignancies from images has attracted many researchers. Unlike many machine-learning approaches, such as artificial neural networks, genetic programming (GP) automatically evolves models with flexible representation. GP successfully provides effective solutions using its intrinsic ability to select prominent features (i.e., feature selection) and build new features (i.e., feature construction). Existing approaches have utilized GP to construct new features from the complete set of original features and the set of operators. However, the complete set of features may contain redundant or irrelevant features that do not provide useful information for classification. This study aims to develop a two-stage GP method, where the first stage selects prominent features, and the second stage constructs new features from these selected features and operators, such as multiplication in a wrapper approach to improve the classification performance. To include local, global, texture, color, and multiscale image properties of skin images, GP selects and constructs features extracted from local binary patterns and pyramid-structured wavelet decomposition. The accuracy of this GP method is assessed using two real-world skin image datasets captured from the standard camera and specialized instruments, and compared with commonly used classification algorithms, three state of the art, and an existing embedded GP method. The results reveal that this new approach of feature selection and feature construction effectively helps improve the performance of the machine-learning classification algorithms. Unlike other black-box models, the evolved models by GP are interpretable; therefore, the proposed method can assist dermatologists to identify prominent features, which has been shown by further analysis on the evolved models.

Loneliness and mental health related impacts of COVID-19: a narrative review.

Loneliness is the one of the common phase experienced during COVID-19 pandemic. It has impacted mental health of all ages specifically children and adolescents. The aim of this review was to assess level of loneliness and mental health related impacts of COVID-19 among both; children and adolescents. For this literature review, two independent reviewers searched articles on Cochrane library, MEDLINE, Google Scholar and Science-direct. Both MeSH terms and free text terms were used for search purposes between December 01, 2019 and December 30, 2021. A total of 14 studies met inclusion criteria and of these, 8 studies were related to mental health related impacts of COVID-19 pandemic whereas 6 studies involved both aspects i.e. loneliness and mental health among children and adolescents. One study was qualitative, one interventional, and remaining 12 were cross-sectional surveys. The findings of this review suggest an increase in level of loneliness and mental health related impacts during COVID-19 pandemic among children and adolescents. Loneliness, social distancing and internet usage therefore re strongly correlated with mental health related issues including stress, anxiety and depression.

Effectiveness of splitter plate to control fluid forces on a circular obstacle in a transient flow: FEM computations.

The reliability of the usage of a splitter plate (passive control device) downstream of the obstacle, in suppressing the fluid forces on a circular obstacle of diameter [Formula: see text] is studied in this paper. The first parameter of the current study is the attachment of a splitter plate of various lengths [Formula: see text] with the obstacle, whereas the gap separation [Formula: see text] between the splitter plate and the obstacle, is used as a second parameter. The control elements of the first and second parameters are varied from [Formula: see text] to [Formula: see text]. For the attached splitter plates of lengths [Formula: see text] and [Formula: see text], the oscillatory behavior of transient flow at [Formula: see text] is successfully controlled. For the gap separation, [Formula: see text] and [Formula: see text] similar results are obtained. However, it is observed that a splitter plate of too short length and a plate located at the inappropriate gap from the obstacle, are worthless. A computational strategy based on the finite element method is utilized due to the complicated representative equations. For a clear physical depiction of the problem, velocity and pressure plots have been provided. Drag and lift coefficients the hydrodynamic benchmark values are also evaluated in a graphical representation surrounding the obstacle's peripheral surface as well as the splitter plate. In a conclusion, a splitter plate can function to control fluid forces whether it is attached or detached, based on plate length and gap separation between obstacle and plate, respectively.

Computational Analysis of Fluid Forces on an Obstacle in a Channel Driven Cavity: Viscoplastic Material Based Characteristics.

In the current work, an investigation has been carried out for the Bingham fluid flow in a channel-driven cavity with a square obstacle installed near the inlet. A square cavity is placed in a channel to accomplish the desired results. The flow has been induced using a fully developed parabolic velocity at the inlet and Neumann condition at the outlet, with zero no-slip conditions given to the other boundaries. Three computational grids, C1, C2, and C3, are created by altering the position of an obstacle of square shape in the channel. Fundamental conservation and rheological law for viscoplastic Bingham fluids are enforced in mathematical modeling. Due to the complexity of the representative equations, an effective computing strategy based on the finite element approach is used. At an extra-fine level, a hybrid computational grid is created; a very refined level is used to obtain results with higher accuracy. The solution has been approximated using P2 - P1 elements based on the shape functions of the second and first-order polynomial polynomials. The parametric variables are ornamented against graphical trends. In addition, velocity, pressure plots, and line graphs have been provided for a better physical understanding of the situation Furthermore, the hydrodynamic benchmark quantities such as pressure drop, drag, and lift coefficients are assessed in a tabular manner around the external surface of the obstacle. The research predicts the effects of Bingham number (Bn) on the drag and lift coefficients on all three grids C1, C2, and C3, showing that the drag has lower values on the obstacle in the C2 grid compared with C1 and C3 for all values of Bn. Plug zone dominates in the channel downstream of the obstacle with augmentation in Bn, limiting the shear zone in the vicinity of the obstacle.

Confounders in Identification and Analysis of Inflammatory Biomarkers in Cardiovascular Diseases.

Proinflammatory biomarkers have been increasingly used in epidemiologic and intervention studies over the past decades to evaluate and identify an association of systemic inflammation with cardiovascular diseases. Although there is a strong correlation between the elevated level of inflammatory biomarkers and the pathology of various cardiovascular diseases, the mechanisms of the underlying cause are unclear. Identification of pro-inflammatory biomarkers such as cytokines, chemokines, acute phase proteins, and other soluble immune factors can help in the early diagnosis of disease. The presence of certain confounding factors such as variations in age, sex, socio-economic status, body mass index, medication and other substance use, and medical illness, as well as inconsistencies in methodological practices such as sample collection, assaying, and data cleaning and transformation, may contribute to variations in results. The purpose of the review is to identify and summarize the effect of demographic factors, epidemiological factors, medication use, and analytical and pre-analytical factors with a panel of inflammatory biomarkers CRP, IL-1b, IL-6, TNFa, and the soluble TNF receptors on the concentration of these inflammatory biomarkers in serum.

Common postoperative complications after general anesthesia in oral and maxillofacial surgery.

AIM AND OBJECTIVES: Anesthesia is Greek word meaning loss of sensation, and involves painful invasive procedure to be performed with little distress and no pain to the patient. Postoperative anesthetic complications are very common and duration of surgery is frequently cited as major risk factor for postoperative complications. The recognition and treatment of these complications are important when providing good quality care. The purpose of this study was to evaluate mild, moderate, and severe postoperative complications in patients undergoing maxillofacial surgery under general anesthesia and also determine the safety of general anesthesia in healthy and patients with comorbidities. SUBJECTS AND METHODS: This prospective study was conducted in the oral and maxillofacial surgery department. Two hundred and twenty patients who were operated under general anesthesia were taken in study. All relevant past medical and dental records were noted and were supported by preformulated questionnaire and was filled preoperatively and after surgery to 12 weeks. RESULTS: Mild-to-moderate and severe complications were noted. Females showed more complications than males. Most common complications were sore throat, dysphagia, nausea, vomiting, pain, swelling in normal patients, and in patients with comorbidities delayed wound healing, hypertension, and infection were also seen. CONCLUSION: The use of General Anesthesia is considered safe but it has few risks associated with it and past medical conditions should be evaluated preoperatively.

Epidemiology of molecular probes in Xpert MTB/RIF assay in Khyber Pakhtunkhwa, Pakistan.

Regardless of a plethora of advanced diagnostics, TB and drug resistance remains a principal killer. We proposed gold nanoparticles (AuNPs) attached with probes to enhance the efficiency of GeneXpert MTB/RIF assay instead of conventional dye probes for molecular detection. A total of 15,000 samples were collected from TB suspects and subjected to Xpert MTB/RIF assay, where 6800 (45.3%) were detected as MTB positive, 280 (4.3%) were detected to harbor mutations in the RRDR, while invalid /errors were found in 690 (4.6%) cases. The mutations were detected by probe E, 199 (71.1%), while probes B and D, 30 and 26 (10% and 9%), respectively. In the Xpert MTB/RIF Assay were found mutations picked by probes E and B codons 529-533 (71%) and 512-518 (10%), respectively. The fast-rising works of TB nano-diagnostics, of Xpert probes, may improve by the applications of gold nanoparticle probes.

Gene Delivery to the Skin - How Far Have We Come?

Gene therapies are powerful tools to prevent, treat, and cure human diseases. The application of gene therapies for skin diseases received little attention so far, despite the easy accessibility of skin and the urgent medical need. A major obstacle is the unique barrier properties of human skin, which significantly limits the absorption of biomacromolecules, and thus hampers the efficient delivery of nucleic acid payloads. In this review, we discuss current approaches, successes, and failures of cutaneous gene therapy and provide guidance toward the development of next-generation concepts. We specifically allude to the delivery strategies as the major obstacle that prevents the full potential of gene therapies - not only for skin disorders but also for almost any other human disease.

Postpartum urinary retention and its associated obstetric risk factors among women undergoing vaginal delivery in tertiary care hospital.

INTRODUCTION: Postpartum urinary retention (PUR) is not an uncommon consequence of bladder dysfunction after vaginal delivery. Despite its ubiquity, morbidity and discomfort brought to the postpartum women, it's a poorly discussed condition. Patients with Overt PUR are unable to void spontaneously within 6h of vaginal delivery and those with Covert PUR are able to void spontaneously but have a post void residual bladder volume (PVRV) of >150mL. Reported incidences of PUR vary widely ranging from 1.7 %-17.9 %. AIM AND OBJECTIVES: To identify the prevalence and obstetric risk factors for PUR after vaginal delivery in order to identify women with increased risk of PUR. MATERIALS AND METHODS: The PVRV of women who delivered vaginally was measured after the first spontaneous micturition by ultrasonography. PVRV of more than 150mL was considered as covert PUR. Patient data including age, obstetric history, mode of delivery, duration of labor, PVRV were compared between women with and those without PUR. RESULTS: Of 878 included women, the overall prevalence of PUR after vaginal delivery was 12.9 %, the prevalence of overt and covert PUR were 1.8 % and 11.04 % respectively. Parturient who were primigravidae, had perineal injury, instrumental delivery, birth weight >3.5kg and a longer duration of second stage of labor were risk factors for developing PUR. CONCLUSION: Any misdiagnosis or delay in diagnosis of PUR can cause bladder over distension leading to irreversible detrusor damage. Hence vigilant monitoring and early detection of PUR helps in facilitating timely interventions and prevention of immediate and long term sequelae.

Targeted delivery of CRISPR interference system against Fabp4 to white adipocytes ameliorates obesity, inflammation, hepatic steatosis, and insulin resistance.

Obesity is an increasing pathophysiological problem in developed societies. Despite all major progress in understanding molecular mechanisms of obesity, currently available anti-obesity drugs have shown limited efficacy with severe side effects. CRISPR interference (CRISPRi) mechanism based on catalytically dead Cas9 (dCas9) and single guide RNA (sgRNA) was combined with a targeted nonviral gene delivery system to treat obesity and obesity-induced type 2 diabetes. A fusion peptide targeting a vascular and cellular marker of adipose tissue, prohibitin, was developed by conjugation of adipocyte targeting sequence (CKGGRAKDC) to 9-mer arginine (ATS-9R). (dCas9/sgFabp4) + ATS-9R oligoplexes showed effective condensation and selective delivery into mature adipocytes. Targeted delivery of the CRISPRi system against Fabp4 to white adipocytes by ATS-9R induced effective silencing of Fabp4, resulting in reduction of body weight and inflammation and restoration of hepatic steatosis in obese mice. This RNA-guided DNA recognition platform provides a simple and safe approach to regress and treat obesity and obesity-induced metabolic syndromes.

Risk factors associated with oral manifestations and oral health impact of gastro-oesophageal reflux disease: a multicentre, cross-sectional study in Pakistan.

OBJECTIVE: Gastro-oesophageal reflux disease (GORD) is a relatively common disorder and manifests with extraoesophageal symptoms, such as dental erosions (DE), cough, laryngitis, asthma, and oral soft- and hard-tissue pathologies. This study aimed (1) to identify oral soft and hard-tissue changes in patients with GORD and (2) to evaluate these oral changes as indices for assessing GORD and its severity. SETTING: This cross-sectional study was conducted at four major tertiary care government hospitals, in two metropolitan cities of Pakistan. PARTICIPANTS: In total, 187 of 700 patients who underwent oesophago-gastro-duodenoscopy and having GORD were included in the study. Patients with GORD were divided according to the presence of DE into group A (with DE, chronic/severe GORD) and group B (without DE, mild GORD). Patients who were unconscious and had extremely limited mouth opening were excluded. PRIMARY AND SECONDARY OUTCOME MEASURES: Abnormal conditions and lesions of the oral mucosa were recorded. The impact of oral hard and soft-tissue changes on the oral health-related quality of life was assessed using the Pakistani (Urdu) version of the validated Oral Health Impact Profile-14 (OHIP-14) instrument. RESULTS: Oral submucous fibrosis (66.3%), ulceration (59.4%) and xerostomia (47.6%) were significantly more common in group A (p<0.05). The prevalence of GORD was 26.7%, within which the prevalence of DE was 35.3%. Unhealthy dietary pattern, nausea/vomiting, oesophagitis, xerostomia, ulceration, gingivitis and angular cheilitis showed a statistically significant association with chronic GORD and DE. All subscales of OHIP-14 were positively correlated (p<0.05) in patients with GORD and DE, with notable impact on psychological discomfort (rs=0.30), physical disability (rs=0.29), psychological disability (rs=0.27) and functional limitation (rs=0.20). CONCLUSION: Patients with GORD and DE presented with more severe oral manifestations than did those with GORD and no DE. We recommend timely dental check-ups to assess the severity of both systemic and oral disease.

A Case Of Thrombosis Due To Paroxysmal Nocturnal Haemoglobinuria Presenting At An Early Age.

Paroxysmal Nocturnal Haemoglobinuria (PNH) is an acquired, rare life-threatening disorder characterised by compliment mediated hemolytic anemia, thrombosis and impaired bone marrow function. It occasionally presents in childhood or adolescence. This is a case of a 14-year old female presented with complaints of shortness of breath, palpitation and abdominal pain whose laboratory test results were consistent with Coomb's test negative haemolytic anaemia. Contrast enhanced Computed Tomography Scan (CT scan) of abdomen revealed splanchnic circulation thrombosis as well as partially occluding thrombus in the inferior vena cava. Flow cytometry showed loss of CD59 expression on erythrocytes confirming the diagnosis of paroxysmal nocturnal hemogloubinuria. Supportive treatment was given with haematinics, blood transfusions and anticoagulants. After that, hematopoietic stem cell transplantation was conducted successfully as a permanent treatment. PNH can present at an earlier age and therefore should be included in differential diagnosis of haemolytic anaemia.

Levetiracetam Induced Increase in Creatine Phosphokinase Levels.

Levetiracetam is an antiepileptic drug used for the treatment of generalised or partial seizures, either alone or in a combination therapy. Adverse effects have been reported with its clinical use, including headache, dizziness, liver failure etc. A rare but an important adverse effect is an increase in creatine phosphokinase (CPK) levels with its use. Herein, we present a case of 43-year male, known intravenous (IV) drug abuser with a history of decompressive craniotomy. Patient presented with severe behavioural disorder for which risperidone was given. Five days later, he started having high grade fever, hyperventilation and uncontrolled generalised tonic-clonic seizures (GTCS). After initial management of seizures, levetiracetam was started in combination with topiramate for seizure control. Seizures remained subsided but CPK levels, which were normal at the start of therapy, began to rise and reached tremendous levels of 29,000 mg/dl within a span of a week. Levetiracetam, suspected as a cause of this increase CPK levels, was stopped immediately and the levels returned to baseline within one week. This report provided us with an important step in the management of seizures with levetiracetam.

Mononuclear phagocytes as a target, not a barrier, for drug delivery.

Mononuclear phagocytes have been generally recognized as a barrier to drug delivery. Recently, a new understanding of mononuclear phagocytes (MPS) ontogeny has surfaced and their functions in disease have been unveiled, demonstrating the need for re-evaluation of perspectives on mononuclear phagocytes in drug delivery. In this review, we described mononuclear phagocyte biology and focus on their accumulation mechanisms in disease sites with explanations of monocyte heterogeneity. In the 'MPS as a barrier' section, we summarized recent studies on mechanisms to avoid phagocytosis based on two different biological principles: protein adsorption and self-recognition. In the 'MPS as a target' section, more detailed descriptions were given on mononuclear phagocyte-targeted drug delivery systems and their applications to various diseases. Collectively, we emphasize in this review that mononuclear phagocytes are potent targets for future drug delivery systems. Mononuclear phagocyte-targeted delivery systems should be created with an understanding of mononuclear phagocyte ontogeny and pathology. Each specific subset of phagocytes should be targeted differently by location and function for improved disease-drug delivery while avoiding RES clearance such as Kupffer cells and splenic macrophages.

3D proteochemometrics: using three-dimensional information of proteins and ligands to address aspects of the selectivity of serine proteases.

The high similarity between certain sub-pockets of serine proteases may lead to low selectivity of protease inhibitors. Therefore the application of proteochemometrics (PCM), which quantifies the relationship between protein/ligand descriptors and affinity for multiple ligands and targets simultaneously, is useful to understand and improve the selectivity profiles of potential inhibitors. In this study, protein field-based PCM that uses knowledge-based and WaterMap derived fields to describe proteins in combination with 2D (RDKit and MOE fingerprints) and 3D (4 point pharmacophoric fingerprints and GRIND) ligand descriptors was used to model the bioactivities of 24 homologous serine proteases and 5863 inhibitors in an integrated fashion. Of the multiple field-based PCM models generated based on different ligand descriptors, RDKit fingerprints showed the best performance in terms of external prediction with Rtest2 of 0.72 and RMSEP of 0.81. Further, visual interpretation of the models highlights sub-pocket specific regions that influence affinity and selectivity of serine protease inhibitors.

Plant Alkaloids as Antiplatelet Agent: Drugs of the Future in the Light of Recent Developments.

An alkaloid is a class of naturally occurring organic nitrogen-containing compounds that are frequently found in the plant kingdom. Many alkaloids are valuable medicinal agents that can be utilized to treat various diseases including malaria, diabetics, cancer, cardiac dysfunction etc. Similarly, platelet aggregation beyond the purpose of homeostasis is the underlying cause of blood clotting related diseases. This review presents a thorough understanding of alkaloids as antiplatelet agents with a possible mechanism of action based on the literature of the last decade. In addition, this review will address the antiplatelet activity of alkaloids and their medicinal usage as potent antiplatelet agents with a description of structural relationship activity and possible lead compounds for future drug discovery.

Machine-learning scoring functions to improve structure-based binding affinity prediction and virtual screening.

Docking tools to predict whether and how a small molecule binds to a target can be applied if a structural model of such target is available. The reliability of docking depends, however, on the accuracy of the adopted scoring function (SF). Despite intense research over the years, improving the accuracy of SFs for structure-based binding affinity prediction or virtual screening has proven to be a challenging task for any class of method. New SFs based on modern machine-learning regression models, which do not impose a predetermined functional form and thus are able to exploit effectively much larger amounts of experimental data, have recently been introduced. These machine-learning SFs have been shown to outperform a wide range of classical SFs at both binding affinity prediction and virtual screening. The emerging picture from these studies is that the classical approach of using linear regression with a small number of expert-selected structural features can be strongly improved by a machine-learning approach based on nonlinear regression allied with comprehensive data-driven feature selection. Furthermore, the performance of classical SFs does not grow with larger training datasets and hence this performance gap is expected to widen as more training data becomes available in the future. Other topics covered in this review include predicting the reliability of a SF on a particular target class, generating synthetic data to improve predictive performance and modeling guidelines for SF development. WIREs Comput Mol Sci 2015, 5:405-424. doi: 10.1002/wcms.1225 For further resources related to this article, please visit the WIREs website.