Monkeypox Detection Using CNN with Transfer Learning.

Monkeypox disease is caused by a virus that causes lesions on the skin and has been observed on the African continent in the past years. The fatal consequences caused by virus infections after the COVID pandemic have caused fear and panic among the public. As a result of COVID reaching the pandemic dimension, the development and implementation of rapid detection methods have become important. In this context, our study aims to detect monkeypox disease in case of a possible pandemic through skin lesions with deep-learning methods in a fast and safe way. Deep-learning methods were supported with transfer learning tools and hyperparameter optimization was provided. In the CNN structure, a hybrid function learning model was developed by customizing the transfer learning model together with hyperparameters. Implemented on the custom model MobileNetV3-s, EfficientNetV2, ResNET50, Vgg19, DenseNet121, and Xception models. In our study, AUC, accuracy, recall, loss, and F1-score metrics were used for evaluation and comparison. The optimized hybrid MobileNetV3-s model achieved the best score, with an average F1-score of 0.98, AUC of 0.99, accuracy of 0.96, and recall of 0.97. In this study, convolutional neural networks were used in conjunction with optimization of hyperparameters and a customized hybrid function transfer learning model to achieve striking results when a custom CNN model was developed. The custom CNN model design we have proposed is proof of how successfully and quickly the deep learning methods can achieve results in classification and discrimination.

Epidemiological and hematological investigation of dengue virus infection.

Dengue is a mosquito-borne viral illness that infects humans. For the past few decades, it has been declared a global public health problem. The current study, conducted at the district headquarter hospital (DHQ) Bannu between June to September 2018, was based on the seroprevalence of antibodies against dengue virus serotypes and their hematological parameters among the patients. A total of 1738 individuals suspected of having dengue were diagnosed through NS1, IgG, and IgM antibodies and RT-PCR techniques. Of all the samples, 716 (41.19%) were found to be positive for dengue. A higher infection rate was found in males (65.92%) compared with females (34.07%). The most affected age group was 16-40 years, whereas the most affected tehsil was Bannu, where the DENV-3 serotype was prevalent. The rare serotype (DENV-4) was found in 1% of cases. Symptoms including fever (100%), myalgia (100%), headache (61.31%), vomiting (34.63%), and rashes were common among the dengue patients. However, the mild cases showed fewer clinical signs compared with the severely infected cases. The study also revealed a significant association (P < 0.05) between hematological parameters and dengue infection, showing a significant decrease in TC, eosinophils, neutrophils, and platelets and a significant increase in monocytes and lymphocytes. Based on the current report, it is concluded that patients with the above symptoms and hematological changes may have an increased probability of dengue and should be kept under observation to separate dengue-positive patients and to enhance the treatment process.

CAVVPM: Challenge-Based Authentication and Verification of Vehicle Platooning at Motorway.

As a result of vehicle platooning, advantages including decreased traffic congestion and improved fuel economy are expected. Vehicles in a platoon move in a single line, closely spaced, and at a constant speed. Vehicle-to-vehicle communications and sensor data help keep the platoon formation in place, and the CACC system is responsible for maintaining it. In reality, V2V transmissions are essential for reducing platooning distances while still ensuring their safety and security. It is far more difficult to confirm the veracity of a V2V message's content than it is to verify its integrity and source authentication. Only platoon members can send and receive V2V communications by implementing a practical access control mechanism. The goal is to link a prospective platoon member's digital identification to their actual location inside the unit. A physical challenge-response interaction is used in the CAVVPM process to verify that a prospective platoon member respects the rules. The applicant is asked to perform a series of random longitudinal movements, thus, the protocol's name. Remote attackers cannot join the platoon or send bogus CACC communications because CAVVPM blocks them. CAVVPM is more resistant to pre-recording assaults than previous work, and it can validate that the candidate is precisely behind the verifier in the same lane compared to previous studies.

Association of Longitudinal Glycemia with Diffusion Weighted Imaging Lesions in Spontaneous Intracerebral Hemorrhage.

OBJECTIVES: Higher glycemia on admission has been associated with diffusion weighted imaging (DWI) lesions in patients with spontaneous intracerebral hemorrhage (sICH). However, the influence of longitudinal glycemia after admission and during a patient's hospitalization on DWI lesions in sICH has not been studied. Our aim was to compare longitudinal glycemia in sICH patients with and without DWI lesions. MATERIAL AND METHODS: Glycemia measurements were abstracted on participants enrolled in a prospective observational study examining predictors for DWI lesions in sICH. Univariate analysis was used to compare mean longitudinal glycemia in sICH patients with and without DWI lesions. Logistical regression was used to determine whether mean longitudinal glycemia was predictive of DWI lesions. RESULTS: DWI lesions were found in 60 of the 121 (49.6%) participants. Mean time-to-MRI was 99.6 h (SD ± 89). During this time interval, 2,101 glucose measurements were analyzed with a median number of 7 (IQR 12, 1-261) measurements per patient. Mean longitudinal glycemia was higher in the DWI positive group compared to the DWI negative group until time-to-MRI (132 mg/dL vs 122 mg/dL, p = 0.03). Mean longitudinal glycemia was found to be predictive of DWI lesions (OR 1.02, 95% CI 1.005 to 1.035, p = 0.011). CONCLUSIONS: Mean longitudinal glycemia was higher in sICH patients with DWI lesions compared to those without DWI lesions. Future research into the association between higher glycemia and DWI lesions in sICH may provide insight into a pathophysiologic mechanism.

Knowledge and clinical practices of medical doctors regarding nutrition in cirrhosis patients - A multicentre study from Pakistan.

OBJECTIVE: To determine the nutritional knowledge and clinical practices of physicians regarding nutrition in cirrhosis patients. METHODS: This multi-centre cross-sectional knowledge and practice study was conducted at Pak Emirates Military Hospital, Rawalpindi, Bahria Town International Hospital, Rawalpindi, and District Headquarter Hospital, Mandi Bahauddin, Pakistan, from January to March 2020, and comprised physicians working in wards, out-patient and emergency departments. Data was collected through interviews using a self-generated structured questionnaire. Correct responses were scored 1 and incorrect ones as 0, with a maximum possible score of 13. Data was analysed using SPSS 16. RESULTS: Of the 92 participants, 52(56.5%) were males, while the overall mean age was 28.3±4years and mean years in service 3.7±3 years. The mean score obtained was 5.8±2.1. Of the total, 33(35.9%) physicians had received formal nutritional training, 27(29.3%) were giving regular nutritional counselling and 48(52.2%) wrongly believed in the implementation of restricted diets. A large number of participants incorrectly considered salt 61(66.3%), water 49(53.2%) and lipids/oils 24(26%) to be avoided in ascites. Mean knowledge scores varied significantly for physicians dealing with cirrhosis patients on a daily basis (p<0.001) and those who had received formal training (p=0.003). CONCLUSIONS: The nutritional knowledge of physicians regarding cirrhosis was found to be sub-optimal.

Residents' perspective on the quality of postgraduate training programs in Pakistan - the good, the bad and the ugly.

OBJECTIVES: To assess the satisfaction of trainees towards different attributes of their training programs. METHODS: This cross-sectional survey was carried out by enrolling trainee doctors currently working in Medical, Surgical, Dental and Allied specialties of the country by sending a validated and piloted questionnaire through email. Data collection was done from 1st to 31st January 2021 after taking ethical approval from the concerned authorities. Data was analysed using SPSS v. 19.0. RESULTS: A total of 516 completed responses were received from 15 major cities of the country. The overall perceived satisfaction towards clinical skills (42%), teaching skills (31.4%), personal growth and development (23.6%), research (21%) and supervisor's role (44.2%) were considerably low with the most common causes for non-satisfaction being poor work-life balance (59%), financial instability (54.5%), poor research facilities (53%), poor career guidance (44%) and poor skill development (42.4%) in descending order. Senior years of residency, government and private set-ups, less than four and greater than 13 residents on average with less than three supervisors per department, excessive duty hours and financial instability in-lieu of not doing locums were statistically related to poor satisfaction across majority of the facets of residency as well the overall satisfaction towards training programs. CONCLUSION: There is a tremendous scope for improvement in the recognized and partially acknowledged attributes of our training programs. Yearly feedback surveys involving residents is essential for enlightening the authorities and mitigating the trainees' grievances.

The Amino Terminus of LeuT Changes Conformation in an Environment Sensitive Manner.

Neurotransmitter:sodium symporters are highly expressed in the human brain and catalyze the uptake of substrate through the plasma membrane by using the electrochemical gradient of sodium as the energy source. The bacterial homolog LeuT, a small amino acid transporter isolated from the bacteria Aquifex aeolicus, is the founding member of the family and has been crystallized in three conformations. The N-terminus is structurally well defined and strongly interacts with the transporter core in the outward-facing conformations. However, it could not be resolved in the inward-facing conformation, which indicates enhanced mobility. Here we investigate conformations and dynamics of the N-terminus, by combining molecular dynamics simulations with experimental verification using distance measurements and accessibility studies. We found strongly increased dynamics of the N-terminus, but also that helix TM1A is subject to enhanced mobility. TM1A moves towards the transporter core in the membrane environment, reaching a conformation that is closer to the structure of LeuT with wild type sequence, indicating that the mutation introduced to create the inward-facing structure might have altered the position of helix TM1A. The mobile N-terminus avoids entering the open vestibule of the inward-facing state, as accessibility studies do not show any reduction of quenching by iodide of a fluorophore attached to the N-terminus.

The Influence of Diffusion Weighted Imaging Lesions on Outcomes in Patients with Acute Spontaneous Intracerebral Hemorrhage.

BACKGROUND/OBJECTIVE: Diffusion weighted imaging (DWI) lesions have been well described in patients with acute spontaneous intracerebral hemorrhage (sICH). However, there are limited data on the influence of these lesions on sICH functional outcomes. We conducted a prospective observational cohort study with blinded imaging and outcomes assessment to determine the influence of DWI lesions on long-term outcomes in patients with acute sICH. We hypothesized that DWI lesions are associated with worse modified Rankin Scale (mRS) at 3 months after hospital discharge. METHODS: Consecutive sICH patients meeting study criteria were consented for an magnetic resonance imaging (MRI) scan of the brain and evaluated for remote DWI lesions by neuroradiologists blinded to the patients' hospital course. Blinded mRS outcomes were obtained at 3 months. Logistic regression was used to determine significant factors (p < 0.05) associated with worse functional outcomes defined as an mRS of 4-6. The generalized estimating equation (GEE) approach was used to investigate the effect of DWI lesions on dichotomized mRS (0-3 vs 4-6) longitudinally. RESULTS: DWI lesions were found in 60 of 121 patients (49.6%). The presence of a DWI lesion was associated with increased odds for an mRS of 4-6 at 3 months (OR 5.987, 95% CI 1.409-25.435, p = 0.015) in logistic regression. Using the GEE model, patients with a DWI lesion were less likely to recover over time between 14 days/discharge and 3 months (p = 0.005). CONCLUSIONS: DWI lesions are common in primary sICH, occurring in almost half of our cohort. Our data suggest that DWI lesions are associated with worse mRS at 3 months in good grade sICH and are predictive of impaired recovery after hospital discharge. Further research into the pathophysiologic mechanisms underlying DWI lesions may lead to novel treatment options that may improve outcomes associated with this devastating disease.

Attenuation of vincristine-induced neuropathy by synthetic cyclohexenone-functionalized derivative in mice model.

Vincristine (VCR) is a well-known anticancer drug which frequently induced painful neuropathy and impairs the quality of life of patients. The present study was designed to investigate the alleviative potential of a novel cyclohexenone derivative (CHD), i.e., ethyl 6-(4-methoxyphenyl)-2-oxo-4-phenylcyclohexe-3-enecarboxylate, against VCR-induced neuropathic pain in mice model. VCR was administered intraperitoneally for 10 days in two cycles to induce neuropathic pain. Static and dynamic mechanical allodynia was evaluated using von Frey hair filaments and cotton buds, respectively. Paw thermal hyperalgesia was determined through a hot plate analgesiometer. The tail cold immersion hyperalgesia and paw cold allodynia were determined by available standard protocols. The formalin nociception was induced via subplantar injection of formalin. The antioxidant potential was evaluated via 2,2-diphenyl-1-picrylhydrazyl free radical scavenging activity. The outcome of this study revealed that CHD (30-45 mg/kg) and gabapentin (75 mg/kg) significantly enhanced the paw withdrawal threshold (PWT) and paw withdrawal latency (PWL) in static and dynamic allodynia, respectively, and increased the PWL in thermal hyperalgesia and tail withdrawal latency (TWL) as compared to the VCR-treated group. CHD significantly augmented the paw withdrawal duration (PWD) in paw cold allodynia, while the same compound only increased the paw elevation and paw licking in the delayed phase of formalin nociception. Moreover, CHD significantly inhibited the DPPH free radical scavenging action (IC50 = 56), butylated hydroxytoluene (BHT) (IC50 = 39), and ascorbic acid (IC50 = 2.93). In conclusion, CHD exhibited a profile of potential attenuative effect against the VCR-induced neuropathic pain which might be attributed to its possible antinociceptive and antioxidant effect.

Association of clinical characteristics of patients presenting with influenza like illness or severe acute respiratory illness with development of acute respiratory distress syndrome.

Clinical judgement and suspicion of influenza based on signs and symptoms of influenza-like illness and severe acute respiratory illness are critical for better patient outcome. Whether clinical characteristics of patients are associated with the development of acute respiratory distress syndrome and PCR positivity of samples was the aim of this study. We included all patients (n=37) presenting with influenza like illness (ILI) or severe acute respiratory illness (SARI) to a tertiary care hospital in northwest Pakistan during December 2015 until the end of January 2016. Each patient was assessed for signs and symptoms, clinical features, treatment, complications and outcome of ILI and SARI. Throat or nasopharyngeal swabs were obtained from 36 patient and analyzed for the presence of Influenza virus by quantitative PCR. Patients presenting with ILI or SARI were febrile (p<0.001, one sample t-test), significantly tachypneic (p<0.001) and had critically lower oxygen saturation (p<0.001). Nasal congestion at presentation (p=0.006, chi-square test for association) and infiltrates on chest radiographs (p=0.025) were significantly associated with acute respiratory distress syndrome. Likelihood of the occurrence of ARDS was significantly increased with decrease in oxygen saturation (Odds ratio; 0.75, 95% CI; 0.46, 1.21, p=0.048) and marginally significantly increased in lower age (Odds ratio; 0.82, 95% CI; 0.58, 1.15, p=0.055) and higher white cell count (Odds ratio; 1.001, 95% CI; 0.99, 1.002, p=0.054). The presence of Influenza type A/H1N1pdm09 strains was confirmed in 7/11 patients. However no significant difference was observed in the clinical features and complications of PCR positive and negative patients. Clinical signs and symptoms of influenza-like illness or severe acute respiratory illness significantly predict the development of complications irrespective of the positivity or negativity of laboratory qPCR reports.

A QUALITY BY DESIGN APPROACH: FABRICATION, CHARACTERIZATION AND EVALUATION OF OPTIMIZED TRANSDERMAL THERAPEUTIC SYSTEM FOR ANTIRHEUMATIC LORNOXICAM.

Microemulsion was prepared using several concentrations of selected oil (pine oil), surfactant (cre- mophor RH40), co-surfactant (isopropanol) and water to improve bioavailability by increasing solubility and permeability of lomoxicam, which was then incorporated to carbomer 940 gel base to fabricate microemulsion based gel (MEBG) to sustained permeability for transdermal delivery. Initially, the formulations were investi- gated for physicochemical characteristics, i.e., pH, conductivity, viscosity, refractive index, zeta size, poly-dis- persity index and Atomic Force Microscopy. Also, the significance of the components on in vitro permeability was observed to find out optimum microemulsion (ME,) using Box-Behnken-Design (BBD). MEBG was com- pared for in vitro permeation, stability, skin irritation and anti-inflammatory studies using control gel and in vivo bioavailability study with oral tablet. Microemulsions exhibited the physiological pH (5.35-5.99), oil in water nature (139-185 tsiemens/cm), isotropic (1.3390-1.4166), narrow size (62 nm), homogeneity, Newtonian flow (52-160 centipoise) and spherical shape. Predicted values (Q2, flux, lag time) of optimized microemulsions derived from BBD were in reasonable agreement with experimental values. The formulations were stable and non-irritating to the skin. Significant difference was investigated when comparing percent inhibition of edema of MEBG (80%) and control gel (40%) with respect to standard. The MEBG behavior differed significantly from oral tablet formulation in vivo bioavailability. Such BBD based estimation will reduce time and cost in drug designing, delivery and targeting.

ASSESSMENT OF GUAR AND XANTHAN GUM BASED FLOATING DRUG DELIVERY SYSTEM CONTAINING MEFENAMIC ACID.

We aimed to assess guar and xantban gum based floating drug delivery system containing mefenamic acid. Floating tablets of nefenamic acid were formulated with different concentrations of guar and xanthan gum via wet granulation method. The flow properties of granules that is: bulk density, tapped density, flow rate, Carr index, Hausner's ratio, compressibility index and angle of repose as well as physical parameters of the compressed tablets including: hardness, friability, thickness and swelling indices were determined and found to be good. Xanthan gum was superior to guar gum in maintaining drug release, but a combination of polymers was found to be the best for achieving sustained release up to 12 h due to the synergistic effect of both gums. Drug release mechanism was best explained by Korsmeyer-Peppas model. Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies showed absence of any visible interaction. Stability studies at 40°C (75% RH) showed that the formulation was stable at elevated temperature. It can be concluded that floating tablets can be used as a sustained release matrix due to their superior characteristics.

Assessment of the optimal shoulder outcome score for reverse shoulder arthroplasty.

BACKGROUND: With growing attention being paid to quality and cost-effectiveness in health care, outcome evaluations are becoming increasingly important. This determination can be especially difficult in reverse shoulder arthroplasty (RSA) given the complex pathology and extensive disabilities in this patient population. This study evaluated the use of 3 validated questionnaires used to assess outcomes for RSA. METHODS: Using a database of patients treated with RSA, we assessed preoperative and postoperative Constant-Murley Scores, American Shoulder and Elbow Surgeons Scores, and Subjective Shoulder Values in 148 shoulders. The outcomes at each scoring period were described, and the scores were compared with one another as well as with active range of motion. RESULTS: There were no significant differences in the mean improvement of any of the scores. Improvements in all of the outcome scales were correlated with each other and with improvement in forward elevation but not with external rotation. Multivariate regression analysis the 3 outcome measures was able to predict 38.9% of the variation in improvement in functional outcomes (forward elevation). This was only slightly greater than that provided by improvements in the outcome variable Constant-Murley score alone (36.7%). CONCLUSIONS: The 3 shoulder outcome scores evaluated, regardless of whether they were patient reported or physician based, appear to appropriately reflect improvements after RSA with equal validity. The objective physician-assessed Constant-Murley score had the strongest correlation with function of the arm, and use of a combination of all 3 outcome scores did not increase the ability to predict range of motion compared with using the Constant-Murley score alone.

Cross Culture Examination of Perceived Overqualification, Psychological Well-Being and Job Search: The Moderating Role of Proactive Behavior.

Purpose: This study delves into the intricate interplay between perceived overqualification, job search behavior, psychological well-being, and proactive behavior, within two distinct and diverse work settings. Methods: Drawing upon the Person-Job Fit theory, we investigated these dynamics in two unique samples: Sample 1 encompassed corporate sector employees in the United Arab Emirates (N=409), while Sample 2 comprised IT sector workers in Pakistan (N=337). Hayes PROCESS macro were used to examine the proposed hypotheses and AMOS (Version 28) were conducted to examine model fitness. Results: In Study 1, we established a positive association between perceived overqualification and job search behavior among employees in the UAE corporate sector. Notably, this relationship was mediated by psychological well-being, suggesting that the impact of perceived overqualification on job search behavior is, in part, channeled through its effects on individuals' psychological well-being. Study 2 showed that proactive behavior exhibited a moderating effect on the negative link between perceived overqualification and psychological well-being. Specifically, employees displaying higher levels of proactive behavior demonstrated a less adverse influence of perceived overqualification on psychological well-being. Importantly, this adaptive effect of proactive behavior was found to indirectly influence job search behavior. Discussion: The findings highlight the nature of perceived overqualification in the workplace and its varying impact on employee behavior and well-being across different cultural and work settings. The mediation by psychological well-being and moderation by proactive behavior in these relationships underscores the importance of individual responses to perceived job fit issues. These insights are crucial for understanding employee behavior in diverse work environments and can inform practices for managing perceived overqualification.

Gamification in hospitality: Enhancing workplace thriving and employee well-being.

This study examines the effect of gamification on workplace thriving and employee well-being in the hospitality and tourism organizations, investigating the mediating effects of conflict resolution and working relationships while assessing the moderating influence of top management support. We conducted a time-lagged study with 451 employees from various hospitality and tourism organizations. Our research aimed to understand how gamification affects workplace thriving and employee well-being, with a focus on the mediating roles of conflict resolution and working relationships. We also examined the moderating effect of top management support. Our results demonstrate a positive link between gamification and workplace thriving, as well as a connection between gamification and employee well-being. Conflict resolution was found to mediate the relationship between gamification and workplace thriving, while working relationships mediated the connection between gamification and employee well-being. Additionally, top management support significantly moderated the relationships between gamification, conflict resolution, and workplace thriving.

Unveiling the nexus between perceived overqualification and knowledge hiding: Moderated mediation analysis of job crafting and job boredom.

Purpose: Grounding on relative deprivation theory, this study aimed to investigate the relationship between perceived overqualification (POQ) and knowledge hiding. Furthermore, this study investigated the mediating role of job boredom and the moderating effect of job crafting. Design: /Methodology/Approach: This study employs Hayes' PROCESS model to analyze data obtained from 374 employees working in the hospitality and tourism industry. Findings: The results indicate a positive relationship between POQ, job boredom, and knowledge hiding. These findings suggest that job boredom mediates the relationship between POQ and knowledge hiding. Furthermore, the study showed a moderated mediation path wherein the interaction effect of POQ and job crafting on knowledge hiding was mediated by job boredom. Research limitations/implications: Data were collected from the hospitality and tourism industry, limiting the generalizability of the findings to other sectors. Additionally, the study relied on self-reported measures, which may have resulted in a bias. Practical implications: Conduct thorough job fit assessments during the hiring process to ensure that candidates' qualifications align closely with job requirements. By matching employees' skills and experiences to their job, organizations can reduce perceived overqualification, which may lower job boredom and knowledge hiding tendencies. Originality/value: This study's focus on person-job misfits adds a new layer of insight into employee experiences in the workplace. By examining how mismatches between individuals and their roles contribute to job boredom and knowledge hiding, this study highlights the importance of aligning job responsibilities with employee skills, qualifications, and preferences.

Mitigating potential of polystyrene microplastics on bioavailability, uptake, and toxicity of copper in maize (Zea mays L.).

The coexistence of polystyrene microplastics (PSMPs) and copper (Cu) has become a pressing issue for croplands. However, limited literature is available regarding the interaction of PSMPs with essential micronutrients in Cu-contaminated soils. Therefore, the present study aimed to analyze the immobilization potential of PSMPs for micronutrient bioavailability in soil and Cu toxicity in maize (Zea mays L.). A pot experiment was conducted with maize variety "Islamabad gold" exposed to varying Cu concentrations (0, 50, 100, 200, and 400 mg/kg) and PSMPs (150-250 µm size, 0, 1, and 3% w/w) via soil spiking for 60 days. The concentrations of essential micronutrients (Zn, Cu, Mn, Fe) in soil and plant tissues were measured using an atomic absorption spectrophotometer. Moreover, malondialdehyde (MDA) and antioxidant activities (superoxide dismutase, ascorbate peroxidase, catalase, and peroxidase) were recorded. The concentration of Cu showed significant reduction in post-harvesting soil by 21, 24.8, 27.6, 29.2, and 30.2% from Cu0 to Cu400 mg/kg respectively from pre-sowing soil. On the other hand, the addition of 1%PSMPs and 3%PSMPs declined Cu by 16, 21.6, 24.4, 25.9, 27.8, and 12.6, 16.5, 19.9, 23.2, 25% from Cu0 to Cu400 mg/kg respectively. Maize showed significant improvement in growth under combined exposure of Cu and 3% PSMPs compared to individual exposure. The MDA level was decreased under the combined presence of Cu and PSMPs compared to individual Cu exposure. The percentage difference with 1%PSMPs was 98.1, 95.0, 92.0, 90.0, and 89.6%, while with 3%PSMPs was 93.2, 93.2, 87.7, 81.4, and 79.2% from Cu0 to Cu400 mg/kg respectively. Moreover, the impact of PSMPs was more prominent at a 3% dose compared to a 1% dose. The findings provided significant knowledge about the potential of PSMPs to mitigate Cu toxicity in maize. Future research should incorporate a variety of particle size distributions at natural conditions for variety-specific differences.

First insights into per-and polyfluoroalkyl substance contamination in edible fish species of the Indus water system of Pakistan.

Per- and polyfluoroalkyl substances (PFASs) are a group of emerging contaminants, that have a wide range of applications in industrial and commercial products. The direct discharge of untreated industrial and domestic wastewater into freshwater bodies is a common practice in developing countries, which are the main contributors to PFASs in the aquatic environment. The situation is further worsened due to poor wastewater treatment facilities and weak enforcement of environmental regulations in countries like Pakistan. The current study was designed to assess PFASs contamination in muscle tissues of edible fish species from major tributaries of the Indus System, including Head Panjnad (HP), Head Trimmu (HT), Chashma Barrage (CB), Head Blloki (HB) and Head Qadirabad (HQ). The analysis of target PFAS was performed using ultrahigh-performance liquid chromatography coupled with a quadrupole Orbitrap high-resolution mass spectrometry. The highest levels of ∑17PFASs were observed in S. seenghala, C. mirigala from HB, and C. mirigala from HQ with a mean value of 45.4 ng g-1, 43.7 ng g-1, and 40.8 ng g-1, respectively. Overall, the compositional profile of fish samples was predominated by long-chain PFASs such as PFOA, PFOS, PFHpS, and PFDS. The accumulation of PFASs in fish species is dependent on the physiochemical properties of PFASs, characteristics of the aquatic environment, and fish species. Significant associations of PFASs with isotopic composition (p < 0.05), feeding habits (p < 0.05), and zones (p < 0.05) indicate that dietary proxies could be an important predictor of PFASs distribution among species. The C7-C10 PFASs exhibited bio-accumulative tendency with an accumulation factor ranging from 0.5 to 3.4. However, none of the fish samples had sufficiently high levels of PFOS to cause human health risk (HR < 1). For future studies, it is s recommended to conduct seasonal monitoring and the bioaccumulation pattern along trophic levels of both legacy and emerging PFASs.

Efficacy assessment of novel methanimine derivatives in chronic constriction injury-induced neuropathic model: An in-vivo, ex-vivo and In-Silico approach.

The multicomponent etiology, complex clinical implications, dose-based side effect and degree of pain mitigation associated with the current pharmacological therapy is incapable in complete resolution of chronic neuropathic pain patients which necessitates the perpetual requirement of novel medication therapy. Therefore, this study explored the ameliorative aptitude of two novel methanimine imitative like (E)-N-(4-nitrobenzylidene)-4­chloro-2-iodobenzamine (KB 09) and (E)-N-(4-methylbenzylidene)-4­chloro-2-iodobenzamine (KB 10) in chronic constriction injury (CCI) of sciatic nerve induced neuropathic pain in rat model. Standard behavioral tests like dynamic and static allodynia, cold, thermal and mechanical hyperalgesia along with rotarod activity were performed at various experimental days like 0, 3, 7, 14 and 21. Enzyme linked immunosorbent assay (ELISA) on spinal tissue and antioxidant assays on sciatic nerve were executed accompanied by molecular docking and simulation studies. Prolonged ligation of sciatic nerve expressively induced hyperalgesia as well as allodynia in rats. KB 09 and KB 10 substantially attenuated the CCI elicited hyperalgesia and allodynia. They significantly reduced the biomarkers of pain and inflammation like Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in ELISA and while enhanced the GSH, SOD and CAT and diminished the MDA levels during antioxidant assays. KB 09 displayed -9.62 kcal/mol with TNF-α and -7.68 kcal/mol binding energy with IL-6 whereas KB 10 exhibited binding energy of -8.20 kcal/mol with IL-6 while -11.68 kcal/mol with TNF-α and hence both trial compounds ensured stable interaction with IL-6 and TNF-α during computational analysis. The results advocated that both methanimine derivatives might be novel candidates for attenuation of CCI-induced neuropathic pain prospects via anti-nociceptive, anti-inflammatory and antioxidant mechanisms.

Association between non-alcoholic fatty liver disease and coronary artery disease outcomes: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the association between non-alcoholic fatty liver disease (NAFLD) and cardiovascular outcomes, including angina, coronary artery disease (CAD), coronary artery calcification (CAC), myocardial infarction (MI), and calcified coronary plaques. METHODS: A comprehensive search of databases, including PubMed, EMBASE, and Cochrane Library, was conducted up to January 2023. Studies were included investigating the relationship between NAFLD and cardiovascular outcomes in adult populations. Exclusion criteria were studies on animals, pediatric populations, and those not published in English. Two reviewers assessed the risk of bias in the included studies using the Newcastle-Ottawa Scale. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using random-effects models. RESULTS: The meta-analysis included 32 studies with a total of 5,610,990 participants. NAFLD demonstrated significant associations with increased risks of angina (Relative Risk (RR): 1.45, 95% CI: 1.17, 1.79), CAD (RR: 1.21, 95% CI: 1.07, 1.38), CAC >0 (RR: 1.39, 95% CI: 1.15, 1.69), and calcified coronary plaques (RR: 1.55, 95% CI: 1.05, 2.27). However, no significant association was found between NAFLD and CAC >100 (RR: 1.16, 95% CI: 0.97, 1.38) or MI (RR: 1.70, 95% CI: 0.16, 18.32). CONCLUSION: The meta-analysis demonstrated a significant association between NAFLD and cardiovascular outcomes independent of conventional cardiovascular disease (CVD) risk factors. These findings emphasize the importance of prevention, early detection, and proper management of NAFLD.