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This study focused on analyzing the pharmacological activities of AgNPs synthesized from an aqueous plant extract of Anchusa arvensis . The effectiveness of AgNPs was evaluated for protein kinase inhibition, antioxidant, antibacterial, and antifungal activities. The AgNPs and plant were used to regulate the protein kinase activity using the liquid TSB and ISP4 medium protein kinase inhibition study demonstrated that nanoparticles exhibited a larger zone of inhibition (9.1 ± 0.8) compared to the plant extract (8.1 ± 0.6). The antioxidant activity was assessed using DPPH reagent, and the results indicated that AgNPs displayed potent free radical scavenging properties. In terms of antibacterial activity, AgNPs showed higher efficacy against Enterobacter aerogens (20.1 ± 0.9), Bordetella bronchiseptaca (19.1 ± 0.9), and Salmonella typhimurium (17.2 ± 0.8) at 4 mg/mL. The antifungal activity of AgNPs was prominent against Aspergillus fumagatus (14.1 ± 0.9), Mucor species (19.2 ± 0.8), and Fusarium solani (11.2 ± 0.8) at 20 mg/mL. These findings suggest that AgNPs possess multiple beneficial properties, including bactericidal/fungicidal effects, protein kinase inhibition, and potential free radical scavenging abilities. Therefore, AgNPs have potential applications in various fields, such as biomedicine and industry, due to their ability to counteract the harmful effects of free radicals., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Trauma during pregnancy presents multifaceted risks to both the developing fetus and the expectant mother due to pregnancy-induced physiological adaptations that affect the response to traumatic injuries. The infrequent occurrence of cardiac arrest during pregnancy necessitates interventions such as perimortem cesarean section (PMCS), now termed resuscitative hysterotomy. While early resuscitative hysterotomy focused primarily on fetal survival, more recent literature reports substantial maternal benefits. Resuscitative hysterotomy can lead to the restoration of maternal pulse and blood pressure within minutes and has shown potential to improve maternal outcomes. RH has been demonstrated to aid in fetal and maternal survival in hemodynamic unstable pregnant patients before cardiovascular collapse. The linguistic change from PMCS to resuscitative hysterotomy is a shift towards maternal-centric approaches and survival., Objective: In this series, we evaluate the outcomes of resuscitative hysterotomy performed before or after cardiovascular collapse to maximize maternal survival while concurrently optimizing fetal outcomes., Methods: We performed a retrospective case series review of 4 consecutive pregnant trauma patients who underwent RH due to hemodynamic instability. In addition, we conducted a descriptive analysis of all pregnant patients from 2013 to May 2024 who presented due to a traumatic injury but did not require a RH., Results: The average age of patients undergoing RH was 26.5 ± 6.8 years. All patients were in the third trimester with a mean gestational age of 32.3 ± 0.5 weeks. Fifty percent (50 %) of patients were involved in motor vehicle accidents, one (25 %) pedestrian was hit by a vehicle, and one (25 %) had GSW to the head. The median time to RH was 14.5 min. The mean estimated blood loss (EBL) was 625 mL ±108.9 mL. The maternal survival rate was 50 %, with a fetal survival rate of 100 %. Three patients achieved hemodynamic stability; however, one of the patients progressed to death by neurological criteria. Therefore, we achieved 50 % of maternal survival. A resuscitative hysterotomy was performed due to early signs of maternal hemorrhagic shock and suggestive features of ongoing bleeding (persistent maternal tachycardia despite adequate analgesia and resuscitation, persistent maternal bradycardia, gradual decline of BP, and FHR abnormalities) in three patients. The remaining patient was found to have cardiac arrest at the scene with a brief return of spontaneous circulation and received resuscitative hysterotomy in the ED to restore cardiovascular function., Conclusion: RH in pregnant patients with traumatic injury and impending hemorrhagic shock or cardiovascular collapse may provide maternal survival benefits by supporting circulatory function and promoting resuscitation with no additional risks to fetal outcomes. Quick decision-making is crucial to the implementation of this life-saving procedure. Further research with a more significant number of patients is needed to validate the efficacy of RH in maximizing maternal survival. This case series adds to the evolving literature on RH, shedding light on practical aspects and maternal outcomes to inform ongoing discussions and strategies for maternal cardiopulmonary resuscitation., Competing Interests: Declaration of competing interest None., (Copyright © 2024. Published by Elsevier Ltd.)

Background: The interaction between visitors and captive birds is complex, with a potential impact on bird's behavior and welfare. Understanding this interaction is essential for effective conservation and management., Methods: We conducted a study at the University of Haripur's pheasantry in Khyber Pakhtunkhwa, Pakistan to investigate the effects of visitor numbers, duration of visitor presence, and climatic factors on the behavior of female pheasants. We observed the state and events of feeding, hiding, and moving behaviors of 16 randomly selected individuals from five species., Results: The mixed-effects modeling results show that visitors (VT), visitors' presence duration (VPD), and temperature (TP), significantly influence feeding events ( p < 0.001), feeding duration ( p < 0.001), hiding events ( p < 0.001) and hiding duration of female pheasants ( p < 0.001). The moving events of pheasants were also significantly affected by both VT and VPD (VT: p = 0.002, VPD: p < 0.001). Moreover, under high visitor conditions, the impact of VPD on the behavior of female pheasants was more pronounced ( p < 0.001). Additionally, our result reveals that different species of pheasants exhibit varying sensitivities to human factors and climatic factors. For instance, the two species of female pheasants with the highest feeding and hiding events were the Green pheasant ( Phasianus versicolor ) and the Ring-necked pheasant ( Phasianus colchicus ). While hiding duration of female Green pheasants, female Golden pheasants ( Chrysolophus pictus ), and female Silver pheasants ( Lophura nycthemera ) was longer than those of others. The mean number of moving events was highest in females of Ring-necked, followed by Golden pheasants. The female Indian peafowl ( Pavo cristatus ) and female Silver pheasants were the birds with the longest moving duration., Conclusion: Our findings highlight the necessity for customized management strategies, to lessen the effects of human disturbances in pheasantries. For a thorough understanding of these interactions, more studies involving larger sample sizes and a wider variety of species are advised., Competing Interests: The authors declare that they have no competing interests., (© 2024 Bibi et al.)

Background: This study aimed to test the efficacy of patient-centered self-management intervention (PACE-SMI) to improve HbA1c, self-efficacy, and self-care behaviors in adults with type 2 diabetes mellitus (T2DM)., Methods: In this multicenter, parallel two-arm randomized controlled trial, 612 adults with T2DM and HbA1c ≥ 7% were enrolled and assigned to the control group (n = 310) and the intervention group (n = 302) using stratified permuted block randomization. The control group received usual care, whereas the intervention group received usual care plus nurse-led, theory-driven, culturally tailored PACE-SMI, comprising eight weekly sessions of individualized education, counseling, behavioral training, and home visit. Outcomes were assessed at baseline, postintervention, and 3 months follow-up., Results: Data at 3 months were provided by 583 participants (control: n = 295, intervention: n = 288). Per-protocol analysis showed that the intervention group had a lower mean HbA1c (8.49% [standard deviation (SD), 1.58]) than the control group (8.74% [SD, 1.62]), with small yet statistically significant mean difference of 0.25% (95% confidence interval [CI], -0.01 to 0.51; Cohen's d = 0.16; p = 0.03). Self-efficacy and self-care behaviors significantly improved in the intervention group (116.89 [SD, 25.50] and 70.01 [SD, 17.97]) compared to the control group (75.43 [SD, 18.99] and 51.54 [SD, 12.04]), with mean differences of 41.48 (95% CI, 37.83-45.13; Cohen's d = 1.84; p < 0.0001) and 18.56 (95% CI, 16.08-21.04; Cohen's d = 1.22; p < 0.0001), respectively. Linear regression analysis indicated the effect of PACE-SMI on HbA1c was significantly mediated by improvements in self-efficacy and self-care behaviors (R 2  = 0.232, p < 0.001)., Conclusion: PACE-SMI led to modest but significant improvement in HbA1c and substantial enhancements in self-efficacy and self-care behaviors in adults with T2DM., (© 2024 The Author(s). Journal of Diabetes published by Ruijin Hospital, Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Herein we report the simultaneous detection of dopamine (DA) and uric acid (UA) using polydopamine (PDA) functionalized FeTiO 3 nanohexagons. The nanohexagons were hydrothermally synthesized and subsequently functionalized with PDA in a Tris-buffer solution. The PDA functionalized nanostructure was characterized using X-ray diffraction (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared (FTIR), respectively. The SEM and TEM investigations revealed the presence of FeTiO 3 nanohexagons along with a peripheral coating of PDA over the nanostructures. The XRD pattern confirmed the formation of the ilmenite structure, while the chemical structure was investigated through XPS and FTIR respectively. Using cyclic voltammetry (CV) the efficacy of FeTiO 3 -PDA electrode was evaluated toward DA oxidation. The enhanced activity of the functionalized electrode in DA oxidation, as compared to the untreated FeTiO 3 , may be attributed to the significant presence of hydroxyl, amine, and imine functional groups over the polymer layer. Differential pulse voltammetry (DPV) was utilized for the detection of DA and UA. With a linear range of 50 μM to 250 μM, the detection limits of 0.30 μM and 4.61 μM were determined for DA and UA, respectively. The peak separation of 263 mV between DA and UA demonstrates the sensor's remarkable selectivity. In addition, the study displayed the ability to detect both DA and UA simultaneously, and the validity of the sensor was evaluated in serum samples, respectively., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Aczel-Alsina t-norm and t-conorm are intrinsically flexible and endow Aczel-Alsina aggregation operators with greater versatility and robustness in the aggregation process than operators rooted in other t-norms and t-conorm families. Moreover, the linear Diophantine fuzzy set (LD-FS) is one of the resilient extensions of the fuzzy sets (FSs), intuitionistic fuzzy sets (IFSs), Pythagorean fuzzy sets (PyFSs), and q-rung orthopair fuzzy sets (q-ROFSs), which has acquired prominence in decision analysis due to its exceptional efficacy in resolving ambiguous data. Keeping in view the advantages of both LD-FSs and Aczel-Alsina aggregation operators, this article aims to establish Aczel-Alsina operation rules for LD-FSs, such as Aczel-Alsina sum, Aczel-Alsina product, Aczel-Alsina scalar multiplication, and Aczel-Alsina exponentiation. Based on these operation rules, we expose the linear Diophantine fuzzy Aczel-Alsina weighted average (LDFAAWA) operator, and linear Diophantine fuzzy Aczel-Alsina weighted geometric (LDFAAWG) operator and scrutinize their distinctive characteristics and results. Additionally, based on these aggregation operators (AOs), a multi-criteria decision-making (MCDM) approach is designed and tested with a practical case study related to forecasting weather under an LD-FS setting. The developed model undergoes a comparative analysis with several prevailing approaches to demonstrate the superiority and accuracy of the proposed model. Besides, the influence of the parameter Λ on the ranking order is successfully highlighted., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Author(s).)

The aim of the current study was to explore the potential of human plasma-derived exosomes as versatile carriers for drug delivery by employing various active and passive loading methods. Exosomes were isolated from human plasma using differential centrifugation and ultrafiltration method. Drug loading was achieved by employing sonication and freeze thaw methods, facilitating effective drug encapsulation within exosomes for delivery. Each approach was examined for its effectiveness, loading efficiency and ability to preserve membrane stability. Methotrexate (MTX), a weak acid model drug was loaded at a concentration of 2.2 µM to exosomes underwent characterization using various techniques such as particle size analysis, transmission electron microscopy and drug loading capacity. Human plasma derived exosomes showed a mean size of 162.15 ± 28.21 nm and zeta potential of -30.6 ± 0.71 mV. These exosomes were successfully loaded with MTX demonstrated a better drug encapsulation of 64.538 ± 1.54 % by freeze thaw method in comparison 55.515 ± 1.907 % by sonication. In-vitro drug release displayed 60 % loaded drug released within 72 h by freeze thaw method that was significantly different from that by sonication method i.e., 99 % within 72 h (p value 0.0045). Moreover, cell viability of exosomes loaded by freeze thaw method was significantly higher than that by sonication method (p value 0.0091) suggested that there was membrane disruption by sonication method. In conclusion, this study offers valuable insights into the potential of human plasma-derived exosomes loaded by freeze thaw method suggest as a promising carrier for improved drug loading and maintenance of exosomal membrane integrity., (© 2024 The Authors. Published by Elsevier B.V. on behalf of King Saud University.)

Our current study reports the successful synthesis of thiolated chitosan-based nanoparticles for targeted drug delivery of 5-Fluorouracil. This process was achieved through the ionic gelation technique, aiming to improve the efficacy of the chemotherapeutic moiety by modifying the surface of the nanoparticles (NPs) with a ligand. We coated these NPs with hyaluronic acid (HA) to actively target the CD44 receptor, which is frequently overexpressed in various solid malignancies, including breast cancer. XRD, FTIR, SEM, and TEM were used for the physicochemical analysis of the NPs. These 5-Fluorouracil (5-FU) loaded NPs were evaluated on MDA-MB-231 (a triple-negative breast cell line) and MCF-10A (normal epithelial breast cells) to determine their in vitro efficacy. The developed 5-FU-loaded NPs exhibited a particle size within a favorable range (< 300 nm). The positive zeta potential of these nanoparticles facilitated their uptake by negatively charged cancer cells. Moreover, they demonstrated robust stability and achieved high encapsulation efficiency. These nanoparticles exhibited significant cytotoxicity compared to the crude drug (p < 0.05) and displayed a promising release pattern consistent with the basic diffusion model. These traits improve the pharmacokinetic profile, efficacy, and ability to precisely target these nanoparticles, offering a potentially successful anticancer treatment for breast cancer. However, additional in vivo assessments of these formulations are obligatory to confirm these findings., (© 2024. The Author(s).)

Background and Objectives: Erdosteine (Erd) is an antioxidant and anti-inflammatory drug. Vitamin B has been reported to exert anti-inflammatory and antioxidant effects. In this study, we investigated the effect of erdosteine and vitamin B complex on a liver ischemia/reperfusion (I/R) model. Materials and Methods: Thirty-two Wistar Albino male rats weighing 350-400 g were used. The animals were randomly selected and divided into four groups. The groups are as follows: first group (Sham), second group (I/R), third group (I/R + vit B), and fourth group (I/R + vit B + Erd). Rats were subjected to 45 min of hepatic ischemia, followed by a 45 min reperfusion period in the I/R and Vitamin B + Erd groups. An amount of 150 mg/kg/day of erdosteine was given orally for 2 days, and 0.05 mL/kg of i.p. vitamin B complex was given 30 min before the reperfusion. Serum biochemical parameters were measured. Serum Total Antioxidant Status (TAS) and Total Oxidant Status (TOS) were measured, and the Oxidative Stress Index (OSI) was calculated. Hepatic tissue samples were taken for the evaluation of histopathological features. Results : In terms of all histopathological parameters, there were significant differences in the I/R + vit B group and I/R + vit B + Erd group compared with the I/R group ( p < 0.01). In terms of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), TNF-alpha, and IL-6 levels, there were significant differences between the I/R group and treatment groups ( p < 0.01). The lowest TOS and OSI levels were obtained in the treatment groups, and these groups had statistically significantly higher TAS levels compared with the sham and I/R groups ( p < 0.01). Conclusions : As a preliminary experimental study, our study suggests that these agents may have potential diagnostic and therapeutic implications for both ischemic conditions and liver-related diseases. These results suggest that the combination of vit B + Erd may be used to protect against the devastating effects of I/R injury. Our study needs to be confirmed by clinical studies with large participation.

Background and objective Studies assessing the incidence of venous thromboembolic (VTE) events in the setting of massive balanced transfusions and/or tranexamic acid (TXA) infusion have yielded varied outcomes. In light of this, we conducted this study to examine the incidence of VTEs in trauma patients requiring blood products, and to identify the risk factors for VTE and mortality in this population. Methods We performed a retrospective analysis of trauma patients admitted to our level 1 trauma center from January 2013 to September 2023. Clinical characteristics were compared between patients who developed VTE and those who did not. A regression analysis of potential variables associated with the development of VTEs and mortality was performed. Results Among 1305 patients (mean age: 42.4 ± 18.8 years) receiving blood products within the initial 24 hours, 4.3% (56 patients) developed a VTE. Patients with VTE experienced prolonged ICU and hospital stays and ventilation duration (p<0.001). They were also noted to have delayed initiation of VTE prophylaxis (104.2 vs. 50.3 hours, p<.001). Prolonged ventilation >7 days was the sole significant factor associated with VTE in multivariate regression analysis [odds ratio (OR): 6.2, p=0.004]. Early TXA administration (within four hours) showed a higher association with VTE than TXA within 24 hours (OR: 2.1, p=0.07 vs. OR 1.6, p=0.22). Massive transfusion was found to increase VTE risk (OR: 2.65, p<0.001). Severe head and neck (OR: 6.0, p=0.002) and chest (OR: 3.8, p=0.01) injuries were key predictors of mortality, while TXA was not significantly associated with mortality in the multivariate model. Conclusions Our study revealed an elevated risk of VTE in patients requiring massive transfusion protocol (MTP, ≥6 units). Early TXA administration was neither associated with increased VTE risk in MTP patients nor increased mortality risk. Strategies directed at reducing the risk of VTE in massively transfused patients while maintaining the survival benefits of balanced resuscitation and TXA need to be devised., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Halalmeh et al.)

Traumatic brain injury (TBI) is a major public health concern, often leading to significant behavioral and cognitive changes with subsequent impairment in daily functioning and personal interactions. The management of TBI involves a multidisciplinary approach. Neuropsychology has emerged as a critical discipline in assessing, diagnosing, treating, and rehabilitating individuals with TBI. Successful management also requires careful consideration of the patient's cognitive status. Therefore, clinicians must have a comprehensive understanding of the overall clinical picture of the patient at the cognitive and physical level. The primary aim of this research is to explore the role of neuropsychology in TBI management and rehabilitation thoroughly while providing an updated review of the literature. Various neuropsychological assessment tools used to evaluate cognitive functioning in individuals with TBI will be discussed in addition to their validity, reliability, and usefulness in identifying cognitive deficits and developing individualized treatment plans. The findings in this article will have significant implications on the clinical practice of neuropsychology in TBI patients, highlighting the importance of neuropsychological assessment in optimizing the management of this population. The need for increased awareness of neuropsychology among health care professionals, especially in the acute hospital setting, is growing along with the increase in diagnosis of TBI and its complications. Adequate understanding of the complex interplay between cognitive, emotional, and behavioral factors in TBI can inform the development of new interventions and treatment strategies, making it equally as important for patients and their families., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Inflammatory cell infiltration, particularly macrophages, plays a major contribution to the pathogenesis of Rheumatoid Arthritis (RA). Exploiting the overexpression of folate receptors (FR-β) on these recruited macrophages has gained significant attraction for ligand-targeted delivery. Leflunomide (LEF), being an immunomodulatory agent is considered the cornerstone of the therapy, however, its oral efficacy is impeded by low solubility and escalating adverse effects profile. Therefore, in the present work, we developed Folate-conjugated chitosan-chondroitin sulfate nanoparticles encapsulating LEF for selective targeting at inflammatory sites in RA. For this purpose, the folate group was first conjugated with the chitosan polymer. After which, Folate Leflunomide Nanoparticles (FA-LEF-NPs) were synthesized through the ionotropic gelation method by employing FA-CHI and CHS. The polymers CHI and CHS were also presented with innate anti-inflammatory and anti-rheumatic attributes that were helpful in provision of synergistic effects to the formulation. These nanoparticles were further fabricated into a hydrogel, employing almond oil (A.O) as a permeation enhancer. The in vivo studies justified the preferential accumulation of FA-conjugated nanoparticles at inflamed joints more than any other organ in comparison to the free LEF and LEF-NPs formulation. The FA-LEF-NPs loaded hydrogel also ascertained a minimal adverse effect profile with an improvement of inflammatory cytokines expression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Ltd.)

Purpose: Pterygium is a hyaline degenerative disease of the conjunctiva characterized by the progression of fibrovascular connective tissue from the bulbar conjunctiva to the cornea. The mechanism of pterygium formation is still not fully understood. Transient receptor potential (TRP) channels are a group of ion channels with distinct characteristics. Recent indications suggest TRP channels may play a significant regulatory role in pterygium development, but previous studies have mainly focused on in silico analysis. Accordingly, in the present study, we aimed to decipher the expression signatures and role of TRP channels in pterygium development., Methods: The study encompassed a cohort of 45 patients matched for age and gender distribution, comprising 30 individuals with primary pterygium (PP) and 15 individuals with recurrent pterygium (RP). The control group consisted of unaffected conjunctival tissue obtained from the same set of patients. High-throughput screening of differentially expressed TRP channels in pterygium tissues was achieved with the help of Fluidigm 96.96 Dynamic Array Expression Chip and reactions were held in BioMark™ HD System Real-Time PCR platform., Results: Statistically significant increases were found in the expression of 21 genes, mainly TRPA1 (p = 0.021), TRPC2 (p = 0.001), and TRPM8 (p = 0.003), in patients with PP, and in TRPC5 (p = 0.05), TRPM2 (p = 0.029), TRPM4 (p = 0.03), TRPM6 (p = 0.045), TRPM8 (p = 0.038), TRPV1 (p = 0.01) and TRPV4 (p = 0.025) genes in RP tissues., Conclusion: Collectively, TRP channel proteins appear to play pivotal roles in both the development and progression of pterygium, making them promising candidates for future therapeutic interventions in patients afflicted by this condition., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Recently in the field of oncology, immune checkpoint inhibitors (ICI) are being increasingly utilized both in clinical trials and in clinical practice. It is a form of biological therapy that targets tumors by activating the immune system, which in turn eliminates proliferating cancer cells. These have numerous immune-related adverse events (irAEs), one of which is myocarditis, which has high rates of mortality. This article was a narrative review of myocarditis related to ICI use.  Studies from the PubMed, Cochrane, and American Society of Clinical Oncology (ASCO) databases were used in writing this review. The databases were searched for original publications for adverse effects related to ICI use and myocarditis specifically. There are numerous published instances of cancer immunotherapy causing myocarditis. ICI therapy has numerous benefits, as it upregulates the immune system to target cancer cells, utilizing the body's own defense mechanisms to target proliferating cells. Myocarditis is a serious side effect, however. Therefore, on balance, these monotherapies are worth using. While this literature review primarily identifies cross-reaction as the main mechanism of myocarditis, there are other possible mechanisms. One proposed mechanism involves a shared antigen between the myocardial tissue and the tumor. This mechanism is called molecular mimicry, where the monoclonal antibody attacks both the myocardial tissue and the tumor cell. Management of ICI-induced myocarditis has not been studied by randomized controlled trials or prospective studies, but based on previous case reports and case series it is mostly treated with steroids initially. An ICI rechallenge after temporary discontinuation appears conceivable in many cases, especially given its therapeutic effects, but only limited data are available on the safety of a rechallenge after an irAE. The lack of RCTs regarding rechallenge with an ICI after irAE, more so specifically about myocarditis, along with the overall results and the complexity involved in such cases once again emphasize the need to make decisions on an individual basis by a multidisciplinary expert working group. At the same time, the focus should also be on publishing more data as the need will grow along with the indications for ICI therapies., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Gul et al.)

Background Depression and anxiety are common psychological conditions associated with polycystic ovarian syndrome (PCOS). It is important to understand the role of various demographic and socio-economic factors that contribute to the development of these psychological conditions. Objectives The aims of this study were to determine the prevalence of anxiety and depression in women with PCOS and to find the association of various demographic and socio-economic factors with anxiety and depression. Methods This was a single-center cross-sectional study conducted at a tertiary care hospital in Islamabad, Pakistan, from May 2021 to August 2022. All female patients, aged 18 to 40 years and diagnosed with PCOS, who presented to the department of Gynecology during the study period were eligible to be enrolled in the study. The Hospital Anxiety and Depression scale (HADS) was used to determine the level of anxiety and depression in the participants. HADS comprises 14 items scored on a Likert scale ranging from 0 to 3. Seven items correspond to depression and anxiety each. The scores range from 0 to 21 for both domains. A score of 7 or less was considered normal, 8-10 as borderline, and 11 or above as abnormal for both anxiety and depression. Data were analyzed using IBM SPSS Statistics for Windows, Version 26.0 (IBM Corp., Armonk, NY, USA). Results A total of 74 patients with PCOS were included in the study. The mean age of all the participants was 26.8 ± 5.2 and the mean body mass index (BMI) was 28.7 ± 5.4. The presence of PCOS-related symptoms was observed in all 74 cases. Menstrual cycle abnormalities were the most common symptom, which was present in 57 (77.0%) cases, followed by weight gain, which was present in 50 (67.6%) cases, and hirsutism, which was present in 41 (55.4%) cases. Diabetes mellitus and hypertension were present only in three (4.1%) and two (2.7%) cases, respectively, and positive family history of depression and/or anxiety was reported by 20 (27%) cases. The mean HAD score was 7 ± 3.8 for depression and 8 ± 3.7 for anxiety. Depression was diagnosed in 13 (17.6%) cases, and anxiety was diagnosed in 15 (20.3%) cases. Depression was found to be significantly associated with BMI (p = 0.015), level of education (p = 0.033), and monthly household income (p = 0.004). Anxiety was found to be associated with employment status (p = 0.009) and current pregnancy (p = 0.007). Rest of the factors such as age, marital status, ethnicity, menstrual irregularities, comorbidities such as diabetes mellitus and hypertension, and a family history of PCOS, anxiety, or depression did not show statistically significant association with either anxiety or depression (p < 0.05). Conclusion Anxiety and depression are common in patients with PCOS. These psychological conditions are associated with various demographic and socio-economic factors such as BMI, level of education, monthly household income, employment status, and pregnancy. It is recommended to involve a multidisciplinary team while managing patients with PCOS to timely identify and treat these psychological conditions in these patients., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2024, Rizwan Khan et al.)

The study investigated the adaptability of Moringa oleifera to saline conditions, focusing on its hormesis behavior. It also examined how various plant growth regulators affected growth, physiological parameters, and bioactive compounds of moringa. In the first phase, different NaCl stress levels (0, 50, 100, 150, 200, and 250 mM) were applied. Notably, significant stimulation was observed at 100 mM stress for growth, total phenolics, total flavonoids and total chlorophyll content while 150 mM stress had a marked inhibitory effect, with survival decreasing at 200 and 250 mM NaCl levels. A 38% reduction in root attributes and shoot length, along with a 55% decrease in leaf score, was observed at 150 mM stress. Total phenolics showed a positive correlation with growth attributes. In the second phase, moringa plants grown under 50, 100, and 150 mM NaCl stress were treated with various plant growth regulators, including cytokinin (50 mg L -1 ), thiourea (5 mM), bezyl amino purine (BAP @50 mg L -1 ), salicylic acid (50 mg L -1 ), hydrogen peroxide (H 2 O 2 @120 μM), or ascorbic acid (50 mg L -1 ) to mitigate adverse effects of salinity. Cytokinin, BAP, and salicylic acid applications improved salinity tolerance, enhancing enzymatic, and non-enzymatic antioxidants, and the abundance of kaempferol, quercetin, hydroxybenzoic, and hydroxycinnamic acids. Pearson correlation and principal component analysis manifested relationships among growth parameters, antioxidant activities, flavonoids, and phenolic acids. This study provides new insights into hormesis management for moringa plants and the influence of plant growth regulators on flavonoids and phenolic acid levels in moringa leaves under saline conditions.

There are recent reports that Ramadan fasting (RF) results in weight gain instead of weight loss. In addition, the data on the efficacy of brief nutrition education on healthy eating practices in Ramadan for better health are scarce. Therefore, a study was conducted to investigate the effects of brief nutrition education before the start of RF on healthy eating practices during RF. For this purpose, a prospective observational study focused on "Dietary Education and Awareness for Ramadan (DEAR)" as an intervention was carried out. The participants ( n  = 74) were recruited and divided into two groups, i.e., intervention and control groups ( n  = 37 each). As an intervention, nutrition education lessons were given before and during RF month. The control group did not attend these nutrition education lessons. Data on anthropometrics, dietary intake, and other parameters were collected at three time points: before, in the end, and 4 weeks after RF. Weight was measured in kg; height, waist circumference (WC), and hip circumference (HC) were measured in cm; and body mass index (BMI) was calculated. Waist-to-hip ratio (WHR) was calculated by dividing the waist value by the hip value. Body composition analysis was performed by the body composition analyzer (BF-907). Blood pressure (BP) was measured using a validated automated blood pressure. A 3-5 ml of venous blood was collected, and plasma and serum were separated. Serum and plasma samples were processed for general blood chemistry (blood lipid profile, glucose, and CRP) within 2 h. CRP was determined by the immunoturbidimetry method using an auto-analyzer. An enzyme-linked immunosorbent assay (ELISA) was used to determine cytokine/chemokines. Adherence to nutrition education (intervention) was assessed. The results show that nutrition education has positive effects on overall nutrition. Significant improvement in dietary adherence to dietary advice in the intervention group was noted. Significant BW loss (mean loss: 1.21 kg) in the intervention group was observed. The majority (63.3%) had lost BW ≥ 1.0 kg. Other changes observed as a result of the intervention included improvements in blood glucose, cholesterol, CRP levels, and systolic and diastolic BP. There was a notable shift in pro- and anti-inflammatory cytokine concentrations: IL-7, IL-4, and TGF-α decreased, while IL-2, TNF-α and resistin, IL-1 RA, IL-17 A, and sCD40 increased. In conclusion, RF resulted in a loss in mean BW and an improvement in related blood chemistry and cytokine profiles. Furthermore, nutrition education before RF resulted in better nutrition practices during RF and a desirable healthy BW, blood lipid, and cytokine profiles., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gul, Khan, Alam, Almajwal, Hussain, Sohail, Hussain, Cena, Shafiq and Aftab.)

Background: The purpose of this study was to determine the results of an arthrodesis technique of the first metatarsophalangeal joint (MTPJ) using a precontoured dorsal plate to correct the hallux valgus deformity., Methods: This was a retrospective analysis of outcomes for first MTPJ arthrodesis performed using 2 precontoured dorsal plates. Radiographic outcomes (intermetatarsal angle [IMA] and hallux valgus angle [HVA]) and patient-reported functional outcome measures (Short-Form 12 and Foot and Ankle Outcome Score) were recorded and compared., Results: Fifty-five patients underwent 77 first MTPJ arthrodeses for severe hallux valgus deformity with associated degenerative changes at the first MTPJ. The mean reduction of the IMA was 5.67° ( P < .05) and the mean reduction of the HVA was 33° ( P < .05). The Short-Form 12 assessment of global health demonstrated a significant improvement in both the physical and mental health composite scores by 16.4 points and 10.4 points ( P < .05), respectively. The Foot and Ankle Outcome Score demonstrated a cumulative decrease of 35% (59.28; P < .05) in all domains., Conclusions: First MTPJ arthrodesis using a precontoured dorsal plate is a successful procedure with a high union rate, low complication rate, and a high level of patient-reported satisfaction., Levels of Evidence: Level III ., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Here, we, for the first time, compared the cardioprotective effects of third-generation vasodilating beta-blocker nebivolol (Neb) and conventional beta-blocker metoprolol (Met) on LPS-induced injury in H9c2 cardiomyoblasts. Our findings denoted that Neb and Met pretreatment diminish LPS-mediated cytotoxicity and oxidative stress. Concomitantly, LPS-triggered inflammatory cytokines activation was significantly suppressed by Neb but not by Met. Pretreatment with either Neb or Met alleviated LPS-mediated mitochondrial impairment by enhancing the expression of genes related to its biogenesis such as PGC-1α, NRF1, and TFAM. On the contrary, Neb but not Met-upregulated mitochondrial fusion-related genes such as OPA, and MFN2. In summary, our findings suggest that Neb and Met treatment significantly ameliorated the LPS-induced cytotoxicity and oxidative stress. Additionally, these findings suggest that Neb but not Met significantly down-regulates LPS-induced proinflammatory factors, probably by enhancing mitochondrial biogenesis and fusion.

Ascorbic acid is a vital biomolecule for human beings. When the body's level of ascorbic acid is abnormal, it can lead to a number of illnesses. Its appropriate concentration is necessary for the oxidation of prostaglandins and cyclic adenosine monophosphate, the production of dopamine, norepinephrine, epinephrine, and carnitine, and the expansion and durability of the collagen triple helix in humans. In the present work, silver nanoparticle synthesis was performed through a paracetamol-mediated approach. Different characterization techniques, such as X-ray diffractometry (XRD), energy dispersive X-ray (EDX), Fourier transform infrared (FTIR), and scanning electron microscopy (SEM), were used to confirm the prepared nanoparticles. Subsequently, the prepared Ag NPs functionalized with an ionic liquid were used as a sensing platform for ascorbic acid in blood serum samples. To achieve the best possible results, the proposed biosensor was optimized with different parameters such as TMB concentration, time, amount of capped nanoparticles (NPs), and pH. The proposed biosensor offers a sensitive and straightforward method for ascorbic acid with a linear range from 2 × 10 -9 to 3.22 × 10 -7 M, an LOD of 1.3 × 10 -8 M, an LOQ of 4.3 × 10 -8 M, and an R 2 of 0.9996, Moreover, applications of the proposed biosensor were successfully used for the detection of ascorbic acid in samples of human plasma, suggesting that Ag NPs with high peroxidase-like activity, high stability, and facile synthesis exhibited promising applications in biomedical fields., Competing Interests: The authors declare no competing financial interest., (© 2023 The Authors. Published by American Chemical Society.)

Introduction: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear., Aims: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients., Conclusion: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation., (© 2023. Italian Society of Hypertension.)

Mucopolysaccharidoses (MPSs) are inherited lysosomal storage disorders (LSDs). MPSs are caused by excessive accumulation of mucopolysaccharides due to missing or deficiency of enzymes required for the degradation of specific macromolecules. MPS I-IV, MPS VI, MPS VII, and MPS IX are sub-types of mucopolysaccharidoses. Among these, MPS III (also known as Sanfilippo) and MPS IV (Morquio) syndromes are lethal and prevalent sub-types. This study aimed to identify causal genetic variants in cases of MPS III and MPS IV and characterize genotype-phenotype relations in Pakistan. We performed clinical, biochemical and genetic analysis using Whole Genome Sequencing (WGS) in 14 Pakistani families affected with MPS III or MPS IV. Patients were classified into MPS III by history of aggressive behaviors, dementia, clear cornea and into MPS IV by short trunk, short stature, reversed ratio of upper segment to lower segment with a short upper segment. Data analysis and variant selections were made based on segregation analysis, examination of known MPS III and MPS IV genes, gene function, gene expression, the pathogenicity of variants based on ACMG guidelines and in silico analysis. In total, 58 individuals from 14 families were included in the present study. Six families were clinically diagnosed with MPS III and eight families with MPS IV. WGS revealed variants in MPS-associated genes including NAGLU, SGSH, GALNS, GNPTG as well as the genes VWA3B , BTD , and GNPTG which have not previously associated with MPS. One family had causal variants in both GALNS and BTD . Accurate and early diagnosis of MPS in children represents a helpful step for designing therapeutic strategies to protect different organs from permanent damage. In addition, pre-natal screening and identification of genetic etiology will facilitate genetic counselling of the affected families. Identification of novel causal MPS genes might help identifying new targeted therapies to treat LSDs., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gul, Firasat, Schubert, Ullah, Peña, Thuesen, Gjesing, Hussain, Tufail, Saqib, Afshan and Hansen.)

Objective: To develop and test the psychometric properties of the Pakistani Critical Thinking Dispositions Scale., Methods: In the item generation phase, constructs of the scale were identified through an in-depth literature review and items were written to measure the constructs. Following this, input of the experts was obtained for content validity index. In the item reduction phase, psychometric properties were measured. Initially, the scale was administered to 580 study participants during May 2018-2020 after approval from the institutional review board. Data was analyzed through SPSS v21, AMOS v21 and Omega extension., Results: First phase identified 54-items for seven constructs including contextual perspective, perseverance, reflection, intellectual integrity, creativity, open-mindedness, and inquisitiveness. Second phase determined KMO test value of 0.974 and Bartlett's test (P-Value < 0.001). The second-order confirmatory factor analysis showed a good fit model explaining 73.37% total variance. Parsimony and baseline comparison indices were favorable. Alpha and Omega value of 42-items was 0.869., Conclusion: Pakistani Critical Thinking Dispositions scale owning seven constructs and 42-items is valid, reliable, and feasible to use in undergraduate nursing education. However, its utilization in other healthcare disciplines can be tested., Competing Interests: Conflict Of Interest: None., (Copyright: © Pakistan Journal of Medical Sciences.)

Here, we describe highly efficient intramolecular hydroarylations mediated by Re 2 O 7 /HReO 4 . Styrene derivatives of different electronic properties have been activated to effect a challenging intramolecular hydroarylation for the facile access to various substituted 1-aryltetralin structures. This method is characterized by mild reaction conditions, broad substrate scope, high chemical yields, and 100% atom economy. The potential synthetic application of this methodology was exemplified by the efficient total synthesis of an iso CA-4 analogue.

Hypertension is a significant public health concern in Saudi Arabia, affecting 28.6% of the population. Despite the availability of effective treatments, optimal blood pressure control is not always achieved, highlighting the need for effective management strategies. This study aimed to evaluate the applicability of home, compared to clinic, blood pressure measurements for managing hypertension in the Qassim region of Saudi Arabia. The study included 85 adults undergoing antihypertensive treatment. Home blood pressure measurements were obtained during the day and the evening using automated oscillometric sphygmomanometers, whereas clinic measurements were taken during clinic hours. Home blood pressure readings were significantly lower than clinic blood pressure readings, with mean differences of 20.4 mmHg and 4.1 mmHg for systolic and diastolic blood pressures, respectively. There was a positive correlation between the clinic systolic and diastolic blood pressures (r = 0.549, p < 0.001) and a weak correlation between the daytime home and clinic systolic blood pressures (r = 0.218, p < 0.05). This study provides insight into the applicability of home blood pressure monitoring, which may aid in the development of more effective hypertension management strategies, particularly the use of morning home blood pressure monitoring to aid treatment decisions through telehealth medicine.

The current study focuses on molecular cloning, expression and structural characterization of growth hormone-receptor (GHR) and its extracellular domain as growth hormone binding protein (GHBP) from the liver of Nili-Ravi buffalo (Bubalus bubalis; Bb). RNA was isolated, genes were amplified by reverse transcriptase-polymerase chain reaction and sequence was characterized. The BbGHR sequence showed three amino acid variations in the extracellular domain when compared with Indian BbGHR. For the production of full length BbGHR and BbGHBP in Escherichia coli (E. coli) BL21 (RIPL) Codon Plus, expression plasmids were constructed under the control of T7lac promoter and isopropyl β-D thiogalactopyranoside was used as an inducer. BbGHR and BbGHBP were expressed as inclusion bodies at ~ 40% and > 30% of the total E. coli proteins, respectively. The BbGHBP was solubilized and refolded by dilution method using cysteine-cystine redox potential. The recombinant BbGHBP was purified and biological activity was checked on HeLa cell lines showing increase cell proliferation in the presence of ovine GH (oGH), hence justifying the increase in the half-life of GH in the presence of BbGHBP. For the molecular interactions of oGH-BbGHBP multiple docking programs were employed to explore the subsequent interactions which showed high binding affinity and presence of large number of hydrogen bonds. Molecular Dynamics studies performed to examine the stability of proteins and exhibited stable structures along with favorable molecular interactions. This study has described the sequence characterization of BbGHR in Nili-Ravi buffaloes and hence provided the basis for the assessment of GH-GHR binding in other Bovidae species., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

The nexus between financial inclusion and carbon emissions is becoming an increasingly important topic, given the augmented awareness of the negative impacts of climate change and carbon emissions on the environment and human health. In this study, we examine the impact of financial inclusion on carbon emissions using the STIRPAT framework for 102 countries from 2004 to 2020. We measure financial inclusion as a composite index, using principal component analysis (PCA) from five financial inclusion proxies. Our robust panel regression estimations suggest an N-Shaped relationship between financial inclusion and carbon emissions. The N-shaped Environmental Kuznets Curve (EKC) implies that the impact of financial inclusion on carbon emission is nonlinear and changes from an inverted U-shaped to a U-shaped. This finding is strong in developing countries and weak in advanced countries. It is also robust across our two normalized measures of financial inclusion as well as across different estimation techniques. These findings suggest adapting a universal environmental strategy that enhances financial inclusion through strong and accessible financial systems, particularly for low-income countries. Our results further suggest that government authorities and policymakers need to develop well-directed and inclusive financial policies that consider the varying levels of governance, regulations, and income across countries., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper, (© 2023 The Authors.)

The outbreak of novel Coronavirus, an enduring pandemic declared by WHO, has consequences to an alarming ongoing public health menace which has already claimed several million human lives. In addition to numerous vaccinations and medications for mild to moderate COVID-19 infection, lack of promising medication or therapeutic pharmaceuticals remains a serious concern to counter the ongoing coronavirus infections and to hinder its dreadful spread. Global health emergencies have called for urgency for potential drug discovery and time is the biggest constraint apart from the financial and human resources required for the high throughput drug screening. However, computational screening or in-silico approaches appeared to be an effective and faster approach to discover potential molecules without sacrificing the model animals. Accumulated shreds of evidence on computational studies against viral diseases have revealed significance of in-silico drug discovery approaches especially in the time of urgency. The central role of RdRp in SARS-CoV-2 replication makes it promising drug target to curtain on going infection and its spread. The present study aimed to employ E-pharmacophore-based virtual screening to reveal potent inhibitors of RdRp as potential leads to block the viral replication. An energy-optimised pharmacophore model was generated to screen the Enamine REAL DataBase (RDB). Then, ADME/T profiles were determined to validate the pharmacokinetics and pharmacodynamics properties of the hit compounds. Moreover, High Throughput Virtual Screening (HTVS) and molecular docking (SP & XP) were employed to screen the top hits from pharmacophore-based virtual screening and ADME/T screen. The binding free energies of the top hits were calculated by conducting MM-GBSA analysis followed by MD simulations to determine the stability of molecular interactions between top hits and RdRp protein. These virtual investigations revealed six compounds having binding free energies of -57.498, -45.776, -46.248, -35.67, -25.15 and -24.90 kcal/mol respectively as calculated by the MM-GBSA method. The MD simulation studies confirmed the stability of protein ligand complexes, hence, indicating as potent RdRp inhibitors and are promising candidate drugs to be further validated and translated into clinics in future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Cardiovascular diseases (CVDs) are the leading cause of death around the world, a trend that will progressively grow over the next decade. Recently, with the advancement of nanotechnology, innovative nanoparticles (NPs) have been efficiently utilized in disease diagnosis and theranostic applications. In this review, we highlighted the benchmark summary of the recently synthesized NPs that are handy for imaging, diagnosis, and treatment of CVDs. NPs are the carrier of drug-delivery payloads actively reaching more areas of the heart and arteries, allowing them novel therapeutic agents for CVDs. Herein, due to the limited availability of literature, we only focused on NPs mechanism in the cardiovascular system and various treatment-based approaches that opens a new window for future research and versatile approach in the field of medical and clinical applications. Moreover, current challenges and limitations for the detection of CVDs has also discussed., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Comparative investigations on environmentally triggered drug delivery and wound healing characteristics of flexible hydrogel composites, Chitosan-Gelatin (C/G) and 2-Hydroxyethyl Methacrylate-Gelatin (H/G); are presented here. These composites, prepared through facile synthesis and curing methods, indicate the potential to smartly respond to the pH changes in wounds by releasing drug simultaneously and aiding in faster healing. An in-vitro investigation of the composite characteristics were included testing for Equilibrium Water Capacity Studies, Fourier Transform Infrared Spectroscopy (FTIR) investigations as well as UV based drug release and gravimetric hydrogel degradation profiles. This was followed by cutaneous application testing of the hydrogel systems in balb-c mice. Observations and testing results indicated the potential applicability of the hydrogel systems as dressings for topical/transdermal applications, provided that further detailed in-vivo characteristics are accounted for.

Background: Lysosomal storage disorders (LSDs) are a group of inherited metabolic diseases, which encompass more than 50 different subtypes of pathologies. These disorders are caused by defects in lysosomal enzymes, transporters, and other non-lysosomal proteins. Mucopolysaccharidosis (MPS) is the most common subgroup of lysosomal storage disorders in which the body is unable to properly breakdown mucopolysaccharides. The aim of the present study was to identify novel genes and pathogenic variants in families from diverse regions of Pakistan with clinically diagnosed mucopolysaccharidosis type I and mucopolysaccharidosis type II. Methods: Clinical diagnosis identified 12 with mucopolysaccharidosis I and 2 with mucopolysaccharidosis II in 14 families and whole genome sequencing (WGS) was performed to identify the causative variations in 15 affected individuals. Twenty-two unaffected individuals including parents or normal siblings of patients were also sequenced. Putative causal variants were identified by co-segregation and functional annotation. Results: Analysis of whole genome sequencing data revealed ten novel and six previously reported variants in lysosomal storage disorders-associated genes ( IDUA, GALNS, SGSH, GAA, IDS , ALDOB, TRAPPC4, MASP1, SMARCAL, KIAA1109, HERC1, RRAS2 ) and a novel candidate gene ( ABCA5 ) for lysosomal storage disorder-like phenotypes, which has previously been associated with symptoms strongly related with lysosomal storage disorder in animal models. Conclusion: Multigenic inheritance was found in several families highlighting the importance of searching for homozygous pathogenic variants in several genes also in families with a high degree of consanguinity., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gul, Firasat, Schubert, Ullah, Peña, Thuesen, Hussain, Staeger, Gjesing, Albrechtsen and Hansen.)

Mitochondrial dysfunction triggered by increased reactive oxygen species (ROS) generation is involved in the pathogenesis and development of cardiac hypertrophy. Nanoceria (cerium oxide nanoparticle) has powerful ROS-scavenging properties and is considered a potential therapeutic option for curbing ROS-related disorders. Here, we explored the signaling mechanism underlying the protective effects of nanoceria against angiotensin (Ang) II-stimulated pathological response in H9c2 cardiomyoblasts. Our data revealed that pretreatment of H9c2 cardiomyoblasts with nanoceria significantly prevented Ang II-stimulated generation of intracellular ROS, aberrant expression of pro-inflammatory cytokines, and hypertrophy markers. Nanoceria pretreatment increased the mRNA levels of genes regulating the cellular antioxidant defense system (SOD2, MnSOD, CAT) in Ang II-treated cells. Furthermore, nanoceria restored mitochondrial function by decreasing mitochondrial ROS, increasing mitochondrial membrane potential (MMP), and promoting the mRNA expression of genes associated with mitochondrial biogenesis (PGC-1α, TFAM, NRF1, and SIRT3) and mitochondrial fusion (MFN2, OPA1). Collectively, these findings demonstrate the protective effects of nanoceria against Ang II-mediated mitochondrial dysfunction and pathological hypertrophy in H9c2 cells.

We aim to investigate the empirical nexus between carbon emissions and financial inclusion for a panel of 74 countries from 2004 to 2020 based on the environment kuznets curve (EKC). Using the advanced panel data analysis framework of Driscoll-Kraay, Generalised linear model, and Prais-Winsten test for the entire sample and heterogeneous subsamples, we document an inverted U-shape relationship between carbon emissions and inclusive financial system. Notably, an inverted U-shape relationship is established in developed, emerging and frontier economies except in standalone economies. Furthermore, the analysis of region-wise subsamples reveals that nonlinear relationship varies across regions. The heterogeneous response of financial inclusion in curtailing environmental degradation provides vital policy insights. It suggests that financial inclusion can be used as a mitigation measure based on well-structured and robust regulatory and legal frameworks. These frameworks would create synergy effects of financial inclusion in designing policies and addressing issues related to sustainable development and climate change., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Objective: Non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes mellitus (T2DM) often coexist and drive detrimental effects in a synergistic manner. This study was designed to understand the changes in circulating lipid and lipoprotein metabolism in patients with T2DM with or without NAFLD. Methods: Four hundred thirty-four T2DM patients aged 18-60 years were included in this study. Fatty liver was assessed by FibroScan. The comprehensive metabolic lipid profiling of serum samples was assessed by using high-throughput proton NMR metabolomics. Results: Our data revealed a significant association between steatosis and serum total lipids in VLDL and LDL lipoprotein subclasses, while total lipids in HDL subclasses were negatively associated. A significant positive association was found between steatosis and concentration of lipids, phospholipids, cholesterol, and triglycerides in VLDL and LDL subclasses, while HDL subclasses were negatively associated. Furthermore, a significant, association was observed between fibrosis and concentrations of lipids, phospholipids, cholesterol, and triglycerides in very small VLDL, large, and very large HDL subclasses. Subgroup analysis revealed a decrease in the concentrations of lipids, phospholipids, cholesterol, and other lipid biomolecules in patients using antilipemic medications. Conclusion: The metabolomics results provide evidence that patients with T2DM with higher steatosis grades have altered lipid metabolomics compared to patients without steatosis. Increased lipid, phospholipids, cholesterol, and triglycerides concentration of VLDL and LDL subclasses are associated with steatosis in patients with T2DM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Alfadda, Almaghamsi, Sherbeeni, Alqutub, Aldosary, Isnani, Al-Daghri, Taylor-Robinson and Gul.)

The study investigates the issues of access, quality, and other major challenges to the online system of education for students in Balochistan during this pandemic of Covid-19. Using the mixed-method design, 100 participants from schools and 7 curriculum experts responded to the survey and the interview questions. Survey results suggested that majority of the schools have enough digital devices, and teachers, to some extent, have skills to use technology in teaching, but limited electricity, funds, weak internet connections, and teacher training were some of the major challenges for them. In interviews, the participants showed disappointment in terms of responsiveness of the curriculum because the textbooks have manifold deficiencies in responding to online education. Considering these deficiencies, proposals were suggested to cope with the existing situation. The findings of the study call for the need on the part of the academia, educational stakeholders, and elected representatives to start joint efforts with national and international donor agencies, technology benefactors and telecommunication operators in developing digital infrastructure to provide students with access to education, quality, and lifelong learning through various pathways. The findings can be generalized to other underdeveloped regions both within and across the country, as the public schools are confronting the same issues and the online system of education has not yet been initiated., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

Background: The rising burden of type 2 diabetes mellitus (DM) and its associated complications is affecting the functional capacity of the individuals, their quality of life and demand for healthcare services with significant economic impact on health care systems and the national economies. Given the enormous health and economic impact, preventing type 2 DM progression and reducing the risk of complications require immediate attention. Evidence from western countries suggests that self-management can slow the progression of type 2 DM and minimize the risk of major complications lowering health-care costs. Effective self-management, however, demands patients' confidence and their full commitment to perform self-care tasks necessitating a patient-centered approach. This study aims to test the efficacy of a patient-centered self-management intervention to improve glycemic control, self-efficacy and self-care behaviors in adults with type 2 DM., Patients and Methods: The study will be carried out as a parallel arm, randomized, controlled trial in four public tertiary care hospitals in Faisalabad, Pakistan. A total of 612 patients with type 2 DM will be recruited and randomly assigned to two groups: a control and an intervention group. The intervention group will receive a patient-centered self-management intervention for eight weeks duration. Subjects will be followed up for three months. The primary outcome will be glycemic control (HbA1c), and secondary outcome variables will include self-efficacy and self-care behaviors all measured at three points in time (baseline, at the end of intervention and at three months follow-up)., Discussion: This randomized controlled trial will provide critical information about the efficacy of patient-centered self-management intervention in improving HbA1c, self-efficacy and self-care behaviors. If successful, this evidence-based care intervention may be provided to all DM patients by updating hospital policies., Trial Registration: NIH: US National Library of Medicine clinicaltrials.gov Identifier: NCT05491252, Shifa Tameer e Millat University Protocol Record: 335-21. Registration date: August 08, 2022. Recruitment began: April 21, 2022. Recruitment completed: July 27, 2022. URL http://www.clinicaltrials.gov., Competing Interests: The authors report no conflicts of interest in this work., (© 2023 Asmat et al.)

Cervical carcinoma is one of the most prevalent gynecological cancers throughout the world. Cisplatin is used as first line chemotherapy for treatment of cervical cancer, but it comes with plethora of side effects. The aim of this study was to develop hyaluronic acid coated, thiolated chitosan nanocarriers using green synthesis approach, for CD44 targeted delivery and sustained release of Cisplatin in cervical cancer cells. After synthesis through ionic gelation method, Zeta analysis showed that the nanoparticle size was 265.9 nm with a zeta potential of +22.3 mV and .226 PDI. SEM and TEM analysis confirmed the spherical shape and smooth surface of nanoparticles. FTIR and XRD showed the presence of characteristic functional groups, successful encapsulation of drug, and crystalline nature of nanoparticles respectively. Drug loading and entrapment efficiency were calculated to be 70.1% ± 1.2% and 45% ± .28% respectively. Analysis of in vitro drug release kinetics showed that drug release followed the Higuchi model at pH 6.8 and 7.4 and Cisplatin release for up to 72 h confirmed sustained release. In vitro analysis on cervical cancer cells HeLa and normal cervical epithelial cells HCK1T was done through cell morphology analysis, trypan blue assay (concentration range of 10-80 μg/ml), and MTT cytotoxic assay (concentration range of 10-90 μg/ml). The results showed a higher cytotoxic potential of HA coated, thiolated chitosan encapsulated Cisplatin (HA-ThCs-Cis NP) nanoformulation as compared to pure Cisplatin in HeLa while in HCK1T, pure Cisplatin showed much higher toxicity as compared to HA-ThCs-Cis nanoformulation. These findings suggest that CD44 targeted delivery system can be a useful approach to minimize offtarget toxicities, give sustained release and better cellular uptake in cancer cells., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kousar, Naseer, Abduh, Kakar, Gul, Anjum and Ahmad.)

Background: Oncolytic viruses are reported as dynamite against cancer treatment nowadays., Methodology: In the present work, a live attenuated oral measles vaccine (OMV) strain was used to formulate a polymeric surface-functionalized ligand-based nanoformulation (NF). OMV (half dose: not less than 500 TCID units; 0.25 mL) was encapsulated in thiolated chitosan and outermost coating with hyaluronic acid by ionic gelation method characterizing parameters was performed., Results and Discussion: CD44 high expression was confirmed in prostatic adenocarcinoma (PRAD) by GEPIA which extracted data of normal and cancer tissue from GTEx and TCGA. Bioinformatics tools confirmed the viral hemagglutinin capsid protein interaction with human Caspase-I, NLRP3, and TNF-α and viral fusion protein interaction with COX-II and Caspase-I after successful delivery of MV encapsulated in NFs due to high affinity of hyaluronic acid with CD44 on the surface of prostate cancer cells. Particle size = 275.6 mm, PDI = 0.372, and ±11.5 zeta potential were shown by zeta analysis, while the thiolated group in NFs was confirmed by FTIR and Raman analysis. SEM and XRD showed a spherical smooth surface and crystalline nature, respectively, while TEM confirmed virus encapsulation within nanoparticles, which makes it very useful in targeted virus delivery systems. The virus was released from NFs in a sustained but continuous release pattern till 48 h. The encapsulated virus titer was calculated as 2.34×107 TCID50/mL units, which showed syncytia formation on post-day infection 7. Multiplicities of infection 0.1, 0.5, 1, 3, 5, 10, 15, and 20 of HA-coated OMV-loaded NFs as compared to MV vaccine on PC3 was inoculated with IC50 of 5.1 and 3.52, respectively, and growth inhibition was seen after 72 h via MTT assay which showed apoptotic cancer cell death., Conclusion: Active targeted, efficacious, and sustained delivery of formulated oncolytic MV is a potent moiety in cancer treatment at lower doses with safe potential for normal prostate cells., Competing Interests: The authors declare no conflict of interest in this study., (© 2023 Naseer et al.)

Zika virus (ZIKV) pandemic and its implication in congenital malformations and severe neurological disorders had created serious threats to global health. ZIKV is a mosquito-borne flavivirus which spread rapidly and infect a large number of people in a shorter time-span. Due to the lack of effective therapeutics, this had become paramount urgency to discover effective drug molecules to encounter the viral infection. Various anti-ZIKV drug discovery efforts during the past several years had been unsuccessful to develop an effective cure. The NS2B-NS3 protein was reported as an attractive therapeutic target for inhibiting viral proliferation, due to its central role in viral replication and maturation of non-structural viral proteins. Therefore, the current in silico drug exploration aimed to identify the novel inhibitors of Zika NS2B-NS3 protease by implementing an e-pharmacophore-based high-throughput virtual screening. A 3D e-pharmacophore model was generated based on the five-featured (ADPRR) pharmacophore hypothesis. Subsequently, the predicted model is further subjected to the high-throughput virtual screening to reveal top hit molecules from the various small molecule databases. Initial hits were examined in terms of binding free energies and ADME properties to identify the candidate hit exhibiting a favourable pharmacokinetic profile. Eventually, molecular dynamic (MD) simulations studies were conducted to evaluate the binding stability of the hit molecule inside the receptor cavity. The findings of the in silico analysis manifested affirmative evidence for three hit molecules with -64.28, -55.15 and -50.16 kcal/mol binding free energies, as potent inhibitors of Zika NS2B-NS3 protease. Hence, these molecules holds the promising potential to serve as a prospective candidates to design effective drugs against ZIKV and related viral infections.

Fungal abetted processes are among the finest approaches for the transformation or degradation and decolorization of dyes in effluents. In this piece of research; biodegradation and metabolic pathways of two toxic dyes Congo Red (CR) and Reactive black 5 (RB5) by two strains of Aspergillus sp. fungus in batch experiments has been investigated. Morphological characteristics of the isolates were observed with both light and electron microscopies. Based on molecular characterization the isolates were identified as Aspergillus flavus and Aspergillus niger. The degradation was also optimized via. operational parameters such as pH, temperature, incubation time, inoculums size, dye concentration, carbon sources and nitrogen sources. Degradation measurements revealed that the isolates effectively degraded 90% and 96% of CR and RB5 respectively. Metabolites were identified with Liquid chromatography-mass spectrometry (LCMS) and degradation pathways of the dyes were proposed. Toxicity assay Phaseolus mungo seeds showed that pure CR and RB5 dyes exhibits significant toxicity whereas fungal treated dye solution resulted in an abatement of the toxicity and cell viability was increased. The results stipulated in this article clearly showed the effectiveness of the isolates on detoxification of CR and RB5 dyes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Background and Objective: Acute kidney injury (AKI) was observed in sick neonates and was associated with poor outcomes. Our cohort represents the neonatal characteristics of those diagnosed with AKI using Kidney Disease: Improved Global Outcome (KDIGO) guidelines., Methodology: A cohort study was conducted in the NICU of FMH from June 2019 to May 2021. Data were collected on a proforma. All continuous variables were not normally distributed and expressed as the median and interquartile range. Categorical variables were analyzed by proportional differences with the Pearson chi-square test or Fisher's exact tests. A multinomial logistic regression model was used to explore the independent risk factors for AKI. Time to the event (death) and the cohort's survival curves were plotted using the Cox proportional hazard model., Results: AKI occurred in 473 (37.6%) neonates. The risk factors of AKI were outborn birth [adjusted odds ratio (AOR): 3.987, 95% confidence interval (CI): 2.564-6.200, p: 0.000], birth asphyxia (AOR: 3.567, 95% CI: 2.093-6.080, p : 0.000), inotropic agent (AOR: 2.060, 95% CI: 1.436-2.957, p : 0.000), antenatal steroids (AOR: 1.721, 95% CI: 1.213-2.443, p : 0.002), central lines (AOR: 1.630, 95% CI: 1.155-2.298, p : 0.005) and intraventricular hemorrhage (IVH)/intracranial hemorrhage/disseminated intravascular coagulopathy (AOR: 1.580, 95% CI: 1.119-2.231, p : 0.009). AKI significantly increases the duration of stay and mortality rates by 16.5% vs. 3.9% in neonates with normal renal function ( p  < 0.001)., Conclusion: About one-third of critically sick neonates had AKI. Significant risk factors for AKI were outborn birth, asphyxia inotropic agents, necrotizing enterocolitis, antenatal steroids central lines, and IVH. AKI is associated with an increased length of stay and increased mortality., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Gul, Anwar, Sheikh, Salamat, Iqbal, Saleem and Fatima.)

Background: Ventilator-associated pneumonia (VAP) is considered the most common hospital acquired infection seen in critical care settings and leading cause of death in Intensive Care Units (ICU). The objective of this study was to assess whether specimen collection impacted diagnosis and if implementation of a VAP bundle would decrease rates at our center., Methods: This single center study design is a retrospective chart review from 2017 to 2020 utilizing the electronic medical record. A pre-/postintervention comparison was performed following implementation of a unit wide VAP bundle and nursing education. Descriptive statistics and continuous variables were analyzed with independent group t -tests, and categorical variables were analyzed with chi-squared tests., Results: Ventilator-associated pneumonia rates decreased in the postimplementation time (20.8%, n = 74 vs 12.2%, n = 15; P = .03). There were no significant differences in the patient profile of those who acquired VAP (ie, males 79.7% vs 86.7%, blunt injuries 63.5% vs 86.7% and severity scores 24.8 vs 25.1, pre vs postimplementation, respectively, all P-values greater than .05)., Discussion/conclusions: Reduction in VAP rates were achieved by implementing a standardized, evidence based, prevention protocol. Further research is warranted as studies have noted that patients requiring mechanical ventilation are at greater risk for VAP than other ICU patients due to the nature of their injuries and increased risk of prolonged mechanical ventilation ≥ 21 days., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Controlled release in drug release kinetics denotes reproducibility and predictability, implying that drug release from delivery devices follows a kinetically predictable and repeatable rate profile from dose to dose. In the current study controlled release tablets of famotidine were prepared by direct compression technique using Eudragit RL 100 polymer. Four different formulations of controlled release tablets of famotidine as (F1, F2, F3 and F4) were prepared by adding different drug to polymer ratio. The pre compression and the post compression of the formulation, characteristics were compared. All results obtained were within the specified standard limits. FTIR studies showed that both the drug and the polymer were compatible. In vitro dissolution study were conducted by Method II (Paddle Method) in phosphate buffer (pH 7.4), at 100rpm. Power law kinetic model was applied for drug release mechanism. The difference similarity of the dissolution profile was determined. The formulation F1 and F2 were released 97 and 96 % in 24 hours and other formulations F3 and F4 were released subsequently 93% and 90% in 24 hours. The results showed that incorporation of Eudragit RL 100 in the formulation of controlled release tablets prolong the drug release rates for 24 hours. The release mechanism was Non-Fickian diffusion mechanism. It was deducted from the current study that the Eudragit RL 100 can be efficiently incorporated in the formulation of controlled release dosage forms with predictable kinetics.

Objectives: Nigella sativa oil is known antiallergic and immunomodulatory effects. We aimed to compare this oil with mometasone furoate, a topical steroid, on a rat model in the prevention of allergic rhinitis symptoms., Methods: A total of 28 two-to-four-month-old Wistar Hannover rats weighing 250-350 g were randomly divided into four groups of seven, which included control, allergic rhinitis, mometasone furoate, and Nigella sativa oil groups. Loss of cilia, an increase of goblet cells, vascular proliferation, inflammatory cell count, eosinophil infiltration, and the degree of hypertrophy in chondrocytes were assessed by light microscopy., Results: The frequency of nasal scratching in the Nigella sativa oil group was found to be significantly lower compared with the allergic rhinitis group (p < 0.05). Typical inflammatory changes seen in allergic rhinitis were not detected in the Nigella sativa oil group. No inflammation was observed in 85.7% of both the healthy control group and the Nigella sativa oil group. In addition, no inflammation was observed in 71.4% of the mometasone furoate group, and this difference was found to be significant compared with the control group (p < 0.05). In addition, eosinophil infiltration, cilia loss, chondrocyte hypertrophy, vascular proliferation, and goblet cell increase were found to be significantly decreased in the mometazone furoate and Nigella sativa oil groups compared to the allergic rhinitis group (p < 0.05)., Conclusion: According to the findings obtained from this study, we found anti-inflammatory and anti-allergic effects of Nigella sativa oil as equally effective as mometasone furoate in the treatment of experimentaly generated allergic rhinitis., Level of Evidence: IV., (Copyright © 2022 Associação Brasileira de Otorrinolaringologia e Cirurgia Cérvico-Facial. Published by Elsevier Editora Ltda. All rights reserved.)

In skin disorders such as microbial and fungal infections, plants and their parts are used. However, there have been very few scientific reports of herbal extracts of the plant Pinus gerardiana to be administered transdermally. The antifungal activity was assessed using poisoned food method against the strains of three pathogenic fungi, namely Alternaria alternata, Curvularia lunata and Bipolaris specifera. Ointment was prepared according to British pharmacopeia and physiochemical evaluation tests were performed. The GCMS was used to determine the chemical composition of the essential oil of Pinus gerardiana. 27 components were obtained. Monoterpenes= 89.97%, Oxygenated monoterpenes = 8.75%, Sesquiterpenes = 2.21% out of 100% of the total composition. The extract of pinus gerardiana showed a zone of inhibition on organism Bipolaris specifera 2.98±0.1µg/ml, Alternaria alternate 3.48±0.21µ/ml and Curvularia lunata 5.04±0.24µg/ml. Ointment was prepared with pH 5.9, conductivity 0.1, viscosity 22.24 and tested for stability. Franz cells were used in vitro and release was determined from 30 minutes to 12 hours.

Vancomycin (VAN) is an effective antibiotic due to its broad-spectrum bactericidal action. High performance liquid chromatography (HPLC), a powerful analytical technique is used for the in vitro/ in vivo quantification of VAN. The current study was aimed to detect the VAN from in vitro as well as the plasma after the extraction from blood of rabbits. The method was developed and validated according to International Council on Harmonization (ICH) Q2 R1 guidelines. Results showed that the peak of VAN was recorded at 2.96 and 2.57 min, respectively in vitro and serum. The coefficient of VAN turned out to be >0.9994 each for in vitro and in vivo samples. VAN was found linear in the range of 6.2-25000ng/mL. The values of accuracy and precision in terms of coefficient of variation (CV) were less than 2%, indicating the validity of the method. The values for LOD and LOQ were estimated to be 1.5 and 4.5ng/mL, correspondingly, which were lower than the values calculated from in vitro media. Furthermore, the score of the greenness found out to be 0.81, depicting good score using AGREE tool. It was concluded that the developed method was found accurate, precise, robust, rugged, linear, detectable and quantifiable at prepared analytical concentrations and could be used for in vitro and in vivo VAN determination.

Background: Non-alcoholic fatty liver disease (NAFLD) is highly prevalent in patients with type 2 diabetes mellitus (T2DM). This study aimed to investigate the prevalence of NAFLD among Saudi patients with T2DM using transient elastography., Methods: A total of 490 patients with T2DM who attended diabetes and primary care clinics were recruited. Controlled attenuation parameter (CAP) and liver stiffness measurements (LSM) were obtained via FibroScan to assess steatosis and fibrosis., Results: Of the examined 490 patients with T2DM, 396 (80.8%) had hepatic steatosis (CAP ≥248 dB/m): 326 (66.5%) had severe steatosis (CAP ≥280 dB/m), while 41 (8.4%) and 29 (5.9%) had mild (CAP ≥248 to <268 dB/m) and moderate steatosis (CAP ≥268 to <280 dB/m), respectively. Of the 396 patients with steatosis, only 35 (8.8%) had LSM ≥7.9 kPa, suggesting the presence of fibrosis, while 361 (91%) had LSM <7.9 kPa, indicating the absence of fibrosis. Increased body mass index (BMI), waist circumference, systolic blood pressure (SBP), and alanine aminotransferase (ALT) were positively associated with both steatosis and fibrosis. After adjusting for age and gender, data from logistic regression analysis demonstrated BMI, waist circumference, SBP, ALT, and high-density lipoprotein (HDL) as significant independent factors for steatosis, while SBP was the only significant predictor associated with fibrosis., Conclusions: Our results demonstrate an increase in prevalence of NAFLD in Saudi patients with T2DM, based on transient elastography and CAP score. The risk of NAFLD appears to be higher in T2DM patients with abdominal obesity, elevated SBP, and increased ALT levels, which supports the screening of these conditions in patients with T2DM., Competing Interests: None