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Introduction: Glioblastoma is a grade IV solid brain tumor and has a 15-month survival rate even after treatment. Glioblastoma development is heavily influenced by retinoblastoma protein (pRB) pathway changes. The blood–brain barrier, drug resistance, and severe toxicity of Temozolamide are key obstacles in treating glioblastoma. Innovative treatments targeting the pRB pathway with efficient delivery vehicles are required to treat glioblastoma. Methods: For this purpose, a library of 691 plant extracts previously tested in vitro for anti-cancerous, anti inflammatory, and anti-proliferative characteristics was created after thorough literature investigations. Compounds were docked against pRB pathway protein ligands using molecular operating environment and chimera. Their nuclear structure and drug-like properties were predicted through Lipinski rule and density functional theory analysis. Physio-chemical characterizations of naked and drug-encapsulated SLNPs assessed size, stability, entrapment efficiency, and drug release rate. Anti-cancer potential of drug and drug- loaded SLNPs was evaluated using U87, U251, and HEK cell lines. Formulations were tested for cancer cell metastatic potential using cell migration assays. Results: Silymarin (Sil) was identified as the most potent compound against CDK4, which was then encapsulated in stearic acid solid lipid nanoparticles (SLNP-Sil). Sil showed decreased cell viability 72 h after treatment against both U87 and U251 cell lines but had negligible cytotoxic effect on HEK-293. IC50 value of Sil was 155.14 µM for U87 and 195.93 µM for U251. Sil and SLNP-Sil effectively inhibited U87 and U251 cell migration 24 h after treatment. Discussion: Our results indicated that Sil and SLNP-Sil are promising therapeutic approaches against glioblastoma and merit in vivo experimental verification using orthotropic xenograft mouse models against glioblastoma. [ABSTRACT FROM AUTHOR]

There is a growing demand for plant-based protein ingredients with improved functionality for use in diverse food and nutraceutical applications. In line with this, the current study aimed to investigate the effect of plant protein-prebiotic (polydextrose) conjugation on the techno-functional properties (emulsification, solubility, fat absorption and foaming) of pea proteins through wet heating Maillard reaction. Pea protein (PeP) was conjugated with polydextrose by incubating the mixture at various process conditions (pea protein: polydextrose mass ratios, temperature, and time). Response surface methodology coupled with Box–Behnken design was used to optimize multiple responses, including conjugation efficiency (CE), emulsifying activity (EAI), and foaming capacity (FC). The pea protein conjugate (optimized value) showed improved solubility throughout a wide pH (2–10) range and higher emulsification activity than pea protein alone. The development of conjugates (PeC) was validated through ultraviolet–visible spectroscopy, FTIR, and o-Phthaldialdehyde (OPA) assay. Browning index, FT-IR spectra, thermal properties, and scanning electron microscopy (SEM) micrographs were analyzed for the conjugate (PeC) obtained at optimized values. The FTIR spectra of the conjugates showed new peaks at 3100–3480 cm−1 and 1,000–1,166 cm−1 indicating conjugation. The Maillard conjugation increased the proportion of β -turn, random coil, accompanied by a decrease in α -helix, and β-sheet. These conformational changes were associated to the improved techno-functional properties of the pea protein upon conjugation, offering potential applications in the formulation of plant-based foods and beverages. [ABSTRACT FROM AUTHOR]

The present study investigates the sustainable influence of human resources (HR) support on job satisfaction and work–life balance among female employees in Saudi Arabia, underlining its significance in advancing social sustainability within the workforce. It seeks to analyze the role of job satisfaction as a mediator and organizational policies as moderators in these relationships. This study analyzed data from a simple random sample of 145 employed women in different sectors in Saudi Arabia, utilizing exploratory and confirmatory factor analyses, as well as inferential statistical methods for hypotheses testing. We conducted an evaluation of mediating and moderating effects in the investigated relationships using the PROCESS macro for SPSS. The findings show a strong positive relationship between HR support, work–life balance, and job satisfaction in Saudi Arabia's female workforce. The mediation function of job satisfaction in the relationship between HR support and work–life balance emphasizes the critical role of positive working experiences in achieving work–life balance. Furthermore, this research highlights organizational policies as a crucial mediator, indicating that implementing supportive and progressive policies might amplify the beneficial impacts of HR practices on work–life balance and job satisfaction. The present study enhances the existing body of knowledge by offering empirical findings on the importance of culturally customized sustainable HR practices and the crucial function of organizational policies in advancing gender equality and achieving a healthy work–life balance. [ABSTRACT FROM AUTHOR]

Hearing loss affects around 5% of the global population. Two preliminary studies have described genetic variants in sporadic individuals with hearing loss from Pakistan. Here we extend these studies to determine the spectrum of variants in a cohort of individuals with no previous history of hearing loss. Individuals with hearing loss born to consanguineous couples were identified from special schools. Audiograms were assessed. DNA from participants negative for GJB2 pathogenic variants was subjected to exome sequencing. Data were filtered to include variants with frequencies < 0.01 in the public databases. The effects of the missense variants on respective amino acids were analyzed by using PyMol software. Among the 44 participants, hearing loss was moderate for two individuals; 14 exhibited moderately-severe hearing loss while 25 had a severe degree of hearing loss. Hearing loss was reported to have been progressive in four participants and was currently profound in three participants. Variants were unambiguously identified in 17 genes, of which the majority affected SLC26A4. CDH23, MYO15A and OTOF were other significant contributors. Deleterious variants detected in two genes suggest new associations for hearing loss. Molecular characterization of hearing loss in our cohort revealed high genetic heterogeneity with a 75% diagnostic rate. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had <50% bone marrow plasma cells (67% vs. 58%; p = 0.018) and R-ISS stage I disease (43% vs. 34%). More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002). Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years. [ABSTRACT FROM AUTHOR]

The present study proposes a generalized ratio estimator for estimating the population mean under the systematic sampling technique by considering auxiliary information and auxiliary attribute. Its bias and Mean Square Error (MSE) expressions have been derived. Mathematical comparisons are made by comparing the proposed estimator with the usual mean estimator, Swain (1964) estimator, Bhal and Tuteja (1991) estimator, and Singh and Singh (1998) estimator, and it is shown that the proposed estimator is more efficient than the previous estimators. A numerical comparison is also performed to demonstrate the superiority of the proposed estimator over the traditional estimators. The technique of ratio estimators based on systematic sampling is used to design an Exponentially Weighted Moving Average (EWMA) control chart. The Control chart is a significant industrial tool for monitoring the process mean. To evaluate performance efficiency Average run lengths (ARL) are obtained in this study. The proposed charts are compared based on out-of-control ARLs. A chart based on the proposed estimator is superior as it detects the shifts earlier than charts based on existing estimators. Empirical work is done to support the study. The suggested efficiency is further addressed utilizing real-life examples and simulations using R-Studio. [ABSTRACT FROM AUTHOR]

This study empirically explores the legitimacy of the Environmental Kuznets Curve (EKC) hypothesis for four economies from the Middle East and North Africa (MENA) region, considering the environmental quality measured by carbon dioxide emissions and national income proxied by real GDP per capita from 1980 to 2018, and employed the ARDL approach. The cointegration results reveal that there persist long-run associations among the series of interest and for each country. Results of ARDL show the validity of the EKC hypothesis for Turkey and unconventionality for the UAE in the long run, while reject its validity for Algeria, Egypt, and the UAE in the short run, and for Turkiya and UAE in the long run, while it is not valid for Algeria. Overall, the empirical estimates on the validity of the EKC hypothesis are found mixed. These empirical findings suggest to design efficient, prudent, and economically feasible environmental protection policies, whereas to start public awareness projects to improve environmental quality in order to achieve sustainable development in the region. [ABSTRACT FROM AUTHOR]

Autologous stem cell transplantation (autoHCT) is considered standard of care for newly diagnosed multiple myeloma (MM). Although most patients eventually progress after autoHCT, a small proportion achieve a durable response. In this retrospective study we included 1576 patients, 244 (15%) of whom were long-term responders (LTR), defined as having a progression-free survival (PFS) of ≥8 years after transplant. Patients in the LTR group were younger than the non-LTR group (median age 58.4 vs. 59.5 years; p = 0.012), less likely to have high-risk cytogenetics (4% vs. 14%; p < 0.001), more often had <50% bone marrow plasma cells (67% vs. 58%; p = 0.018) and R-ISS stage I disease (43% vs. 34%). More patients in the LTR group received post-transplant maintenance (63% vs. 52%; p = 0.002). Patients in the LTR group had higher rates of complete response (CR) at day100 (41% vs. 27%; p < 0.001) and at best post-transplant response (70% vs. 37%; p < 0.001), compared to the non-LTR group. Patients in the LTR groups had a median PFS of 169.3 months and the median overall survival (OS) had not been reached. The leading cause of death in the LTR was disease progression. In conclusion, 15% of patients in the cohort were LTR after upfront autoHCT, with distinct characteristics and a median PFS of more than 14 years. [ABSTRACT FROM AUTHOR]

The therapeutic landscape of the management of stage III non-small cell lung cancer (NSCLC) has drastically evolved with the incorporation of immunotherapy and targeted therapy. Stage III NSCLC accounts for one-third of the cases and the treatment strategy of these locally advanced presentations are diverse, ranging from surgical to non-surgical options; with the incorporation of chemo-immunotherapy, radiation, and targeted therapies wherever applicable. The staging of this disease has also changed, and it is essential to have a strong multidisciplinary approach to do justice to patient care. In this article, we aim to navigate the nuanced approaches in the diagnosis and treatment of stage III NSCLC and expand on the evolution of the management of this disease. [ABSTRACT FROM AUTHOR]

Background: The prognostic significance of minimal residual disease (MRD) status before autologous hematopoietic stem cell transplantation (autoHCT) in patients with multiple myeloma (MM) has not been clearly elucidated. Methods: Retrospective single‐center study of adult MM patients who achieved ≥very good partial response (VGPR) after induction therapy from 2015 to 2021 received upfront autoHCT and had available pretransplant MRD status by next‐generation flow cytometry. The cohort was divided into pretransplant MRD‐negative (MRDneg) and MRD‐positive (MRDpos) groups. Results: A total of 733 patients were included in our analysis; 425 were MRDneg and 308 MRDpos at autoHCT. In the MRDpos group, more patients had high‐risk cytogenetic abnormalities (48% vs. 38%, respectively; p =.025), whereas fewer patients achieved ≥CR before autoHCT (14% vs. 40%; p <.001). At day 100 after autoHCT, 37% of the MRDpos versus 71% of the MRDneg achieved ≥CR, and at best posttransplant response 65% versus 88% achieved ≥CR, respectively. After a median follow‐up of 27.6 months (range, 0.7–82.3), the median PFS was significantly shorter for patients in the MRDpos group compared to the MRDneg group: 48.2 months (95% confidence interval [CI], 0.3–80.5) versus 80.1 months (95% CI, 0.5–80.1), respectively (p <.001). There was no significant difference in overall survival between the two groups (p =.41). Pretransplant MRDpos status was predictive of shorter PFS in multivariate analysis (hazard ratio, 1.80; 95% CI, 1.31–2.46; p <.001). The impact of pretransplant MRD status was retained in most of the examined subgroups. Conclusions: In patients achieving ≥VGPR to induction, pretransplant MRDpos status was associated with a lower CR rate after autoHCT and a shorter PFS. This retrospective single‐center study evaluated the prognostic impact of pretransplant minimal residual disease (MRD) status by next‐generation flow cytometry in 733 multiple myeloma patients who achieved ≥ very good partial response after induction therapy and received upfront autologous hematopoietic stem cell transplantation (autoHCT). Pretransplant MRD positivity was associated with a lower complete remission rate after autoHCT and a shorter progression‐free survival. [ABSTRACT FROM AUTHOR]

Introduction: Neonatal deaths and stillbirths are significant public health concerns in Pakistan, with an estimated stillbirth rate of 43 per 1,000 births and a neonatal mortality rate of 46 deaths per 1,000 live births. Limited access to obstetric care, poor health seeking behaviors and lack of quality healthcare are the leading root causes for stillbirths and neonatal deaths. Rehri Goth, a coastal slum in Karachi, faces even greater challenges due to extreme poverty, and inadequate infrastructure. This study aims to investigate the causes and pathways leading to stillbirths and neonatal deaths in Rehri Goth to develop effective maternal and child health interventions. Methods: A mixed-method cohort study was nested with the implementation of large maternal, neonatal and child health program, captured all stillbirths and neonatal death during the period of May 2014 till June 2018. The Verbal and Social Autopsy (VASA) tool (WHO 2016) was used to collect primary data from all death events to determine the causes as well as the pathways. Interviews were conducted both retrospectively and prospectively with mothers and caregivers. Two trained physicians reviewed the VASA form and the medical records (if available) and coded the cause of death blinded to each other. Descriptive analysis was used to categorize stillbirth and neonatal mortality data into high- and low-mortality clusters, followed by chi-square tests to explore associations between categories, and concluded with a qualitative analysis. Results: Out of 421 events captured, complete VASA interviews were conducted for 317 cases. The leading causes of antepartum stillbirths were pregnancy-induced hypertension (22.4%) and maternal infections (13.4%), while obstructed labor was the primary cause of intrapartum stillbirths (38.3%). Neonatal deaths were primarily caused by perinatal asphyxia (36.1%) and preterm birth complications (27.8%). The qualitative analysis on a subset of 40 death events showed that health system (62.5%) and community factors (37.5%) contributing to adverse outcomes, such as delayed referrals, poor triage systems, suboptimal quality of care, and delayed care-seeking behaviors. Conclusion: The study provides an opportunity to understand the causes of stillbirths and neonatal deaths in one of the impoverished slums of Karachi. The data segregation by clusters as well as triangulation with qualitative analysis highlight the needs of evidence-based strategies for maternal and child health interventions in disadvantaged communities. [ABSTRACT FROM AUTHOR]

This study empirically examines the motives of Indian firms' managers to violate Generally Accepted Accounting Principles (GAAP) and engage in so-called fraudulent accounting. Managers' motivations for fraudulent accounting rather than profit adjustment are empirically analyzed using data from Indian-listed companies. The sample includes 91 firms and the period of study is March 2001 to March 2022. The tests were conducted using single and multiple variables by the empirical methods used in other studies on profit adjustment. In the case of single variables, the tests are the chi-square test of independence for dummy variables and the significance test of the difference between the mean and median for continuous variables. In the case of multiple variables, the sample firms with a dependent variable of 1 and the control firms with a dependent variable of 0 are analyzed using the logit model. The estimation is done by the robust covariance method. The findings indicate that firms that engage in fraudulent accounting are significantly worse off than other firms in terms of their financial position and operating results, have significantly higher financing needs, and significantly more frequently conduct initial public offerings (IPOs). [ABSTRACT FROM AUTHOR]

Probiotics, which offer various health benefits can face challenges in terms of stability during food processing, storage, and gastrointestinal digestion. Therefore, this study aimed to improve the stability and survival of probiotics during various processing conditions and storage. To address this issue, the study was designed to microencapsulate Lactobacillus reuteri DSM 17938 within plant proteins (specifically rice protein (RP) and pea protein (PeP)) and their Maillard reaction conjugated with inulin by spray-drying. The encapsulation efficiency (EE%), stability during storage and temperature, and the viability after simulated gastrointestinal digestion of the microcapsules were examined. The results demonstrate that individual proteins exhibited lower EE%; however, the Maillard conjugates showed increased EE%, with RC (rice protein conjugates) displaying a higher EE% (96.99%) than PC (pea protein conjugates) (92.87%) (p < 0.05). Fourier Transform Infrared Spectroscopy verified the interaction between different functional groups of the proteins and Maillard conjugated and indicated the successful encapsulation of Lactobacillus reuteri DSM 17938 cells. The results also suggested that RC-encapsulated probiotic cells exhibited maximum survival upon gastrointestinal transit, with a decline of only 1.24 and 1.52 log CFU/g after gastric and complete simulated gastrointestinal digestion, respectively. The viability of probiotics encapsulated with RC and PeC showed improvement compared to those encapsulated with RP and PeP, particularly during refrigerated and room temperature storage, thermal challenge, and simulated gastrointestinal transit. Overall, these findings suggest that plant proteins and prebiotic inulin conjugates could serve as promising new encapsulation matrices for the encapsulation of probiotics in food applications. [ABSTRACT FROM AUTHOR]

Identification of genes associated with nonsyndromic hearing loss is a crucial endeavor given the substantial number of individuals who remain without a diagnosis after even the most advanced genetic testing. PKHD1L1 was established as necessary for the formation of the cochlear hair-cell stereociliary coat and causes hearing loss in mice and zebrafish when mutated. We sought to determine if biallelic variants in PKHD1L1 also cause hearing loss in humans. Exome sequencing was performed on DNA of four families segregating autosomal recessive nonsyndromic sensorineural hearing loss. Compound heterozygous p.[(Gly129Ser)];p.[(Gly1314Val)] and p.[(Gly605Arg)];p[(Leu2818TyrfsTer5)], homozygous missense p.(His2479Gln) and nonsense p.(Arg3381Ter) variants were identified in PKHD1L1 that were predicted to be damaging using in silico pathogenicity prediction methods. In vitro functional analysis of two missense variants was performed using purified recombinant PKHD1L1 protein fragments. We then evaluated protein thermodynamic stability with and without the missense variants found in one of the families and performed a minigene splicing assay for another variant. In silico molecular modeling using AlphaFold2 and protein sequence alignment analysis were carried out to further explore potential variant effects on structure. In vitro functional assessment indicated that both engineered PKHD1L1 p.(Gly129Ser) and p.(Gly1314Val) mutant constructs significantly reduced the folding and structural stabilities of the expressed protein fragments, providing further evidence to support pathogenicity of these variants. Minigene assay of the c.1813G>A p.(Gly605Arg) variant, located at the boundary of exon 17, revealed exon skipping leading to an in-frame deletion of 48 amino acids. In silico molecular modeling exposed key structural features that might suggest PKHD1L1 protein destabilization. Multiple lines of evidence collectively associate PKHD1L1 with nonsyndromic mild–moderate to severe sensorineural hearing loss. PKHD1L1 testing in individuals with mild–moderate hearing loss may identify further affected families. [ABSTRACT FROM AUTHOR]

In the present study, the active and intelligent films based on PVOH/Methoxy-kaolin with betalains rich beetroot (Beta vulgaris) extract; extracted at low temperature from fresh beetroot. Betacyanin and betaxanthin were the main component of beetroot extract with an extraction yield of 11.74mg/100g and 7.9mg/100g of fresh beetroot, respectively. Beetroot extract showed that stability of betalains components was maintained from pH range 3–9, and degradation starts under highly alkaline environment i.e. above pH 9. Beetroot extract showed a total phenolic content of 1.4mg GAE/g of fresh beetroot and an antioxidant activity of 93.07%. The physical and functional properties of PVOH/methoxy-kaolin film containing 15%, 20%, 30% (v/v) beetroot extract was characterized using FTIR, XRD, and TGA. An increase in d-spacing of methoxy-kaolin was observed due to the addition of beetroot extract in the PVOH/Methoxy-Kaolin matrix. The addition of beetroot extract showed loss on both thermal and mechanical properties. Methoxy-Kaolin showed positive effects by reducing the water vapor permeability of the colorimetric films. Colorimetric films showed a response to 8mM ammonia solution with a change in color from pink to yellow. Colorimetric films with 30% beetroot extract showed a high response to ammonia solution and high antioxidant activity. [ABSTRACT FROM AUTHOR]

While the body of research on grand challenges (GCs) has grown, our understanding of the role of corporate social innovation (CSI) in tackling exigent GCs, such as the COVID‐19 pandemic, is limited. Based on in‐depth analyses of four cases of CSI in the services sector during the COVID‐19 pandemic, this paper contributes to the GC literature by developing a 3Es framework of the CSI process (i.e., embeddedness, engagement, and enhancement) to illustrate the mechanisms through which exigent GCs can be effectively addressed by firms in the services sector. First, CSI embeddedness in intersectoral partnerships with international organizations based on deep‐rooted trust and collective commitment is found to be a fundamental mechanism for efficiently addressing the COVID‐19 crisis. Second, CSI engagement through the transformation of existing technology and/or the adaption of existing products/services is found to be an important mechanism for meeting pandemic‐induced social needs. Specifically, it is found that leading‐edge technologies such as digital platforms can be rapidly repurposed to enable loosely coupled systems that evolve as a new channel to bring together various stakeholders and thus address this urgent GC. Finally, CSI enhancement supported by managerial agility and participatory governance structure plays a crucial role in enabling CSI to function effectively in the context of exigent GCs. [ABSTRACT FROM AUTHOR]

The prognostic impact of additional copies of chromosome 1q (1q +) on outcomes of newly-diagnosed multiple myeloma (NDMM) patients undergoing autologous transplantation (autoSCT) is unclear. We conducted a retrospective single-center analysis of NDMM patients with 1q21 gain/amplification (3 or ≥4 copies of 1q, respectively) that received autoSCT between 2008–2018. 213 patients were included (79% 1q gain; 21% 1q amplification). The most commonly used induction regimen was bortezomib, lenalidomide, and dexamethasone (41%). At day100 post-autoSCT and at best post-transplant response, 78% and 87% of patients achieved ≥VGPR, and 38% and 50% achieved MRD-negative ≥VGPR, respectively. Median PFS and OS for the entire cohort were 35.5 months and 81.4 months, respectively. On multivariable assessment for PFS, MRD negative ≥VGPR before autoSCT (HR 0.52, p = 0.013) was associated with superior PFS, whereas 1q amplification was associated with inferior PFS (2.03, p = 0.003). On multivariate analysis for OS, achieving MRD negative ≥VGPR at best post-transplant response was associated with superior survival (0.29, p < 0.001), whereas R-ISS III and concomitant del17p or t(4:14) were associated with inferior survival (6.95, p = 0.030, 2.33, p = 0.023 and 3.00, p = 0.047, respectively). In conclusion, patients with 1q+ NDMM, especially 1q amplification, have inferior survival outcomes compared to standard-risk disease after upfront autoSCT, though outcomes are better than other high-risk cytogenetic abnormalities. [ABSTRACT FROM AUTHOR]

Background: Occupational lung diseases are some of the more important yet underdiagnosed pulmonary diseases. The more important reason for this is the lack of knowledge in the general public as well as general practitioners. Marble factories are a very common source of occupational dust exposure leading to derangements in lung functions and lung disorders. Pulmonary function tests are an important step in evaluation of lung functions for the sake of diagnosing various lung disorders1. Objective: To determine the relationship between marble factory workers and lung derangements with respect to their place of job. Methodology: This study was conducted in marble factories located on Warsak road, Hayatabad, and suburbs of Peshawar. 2-step randomization was used to initially select factories and then workers in each factory. A total of 45 factories were selected, followed by selection of 357 workers, 8 in each factory with 4 workers from each of the 2 units (polishing and grinding units). Spirometry was then performed on these workers and the obtained data was analyzed using SPSSv22. Results: All the participants were male with mean age of 33. The workers were divided into 2 groups according to work place as grinding unit and polishing unit, 183 workers were from grinding units while 174 workers were from polishing unit. Out of the 183 workers from grinding unit, 137 had normal spirometric findings, 46 workers had abnormal findings on spirometry. In the polishing unit, out of 174 workers, 151 workers had normal spirometric findings, 23 workers had abnormal spirometric findings. ANOVA test was applied. Workers in grinding unit shows more deranged pulmonary functions as compared to workers in polishing unit. Conclusion: Workers in the grinding unit were at greater risk of developing deranged pulmonary functions as compared to workers in polishing unit. [ABSTRACT FROM AUTHOR]

Purpose: Despite the plethora of research into country-of-origin (COO) effects, research that investigates the cognitive structures behind elite consumers' preferences for foreign brands remains limited. Hence, this study aims to investigate the cognitive structures behind foreign brand preference among professional elites in Sri Lanka. Design/methodology/approach: Using the means-end chain (MEC) theory as the theoretical lens and building on the findings of 30 laddering interviews (semi-structured), a survey was conducted among 311 professional elites to uncover the key elements of the cognitive structures behind foreign brand preference. Findings: The findings revealed that the cognitive structures behind foreign brand preference are influenced by a bundle of brand attributes, brand consequences and personal values of elites', which significantly influence their attitudes towards foreign brands. Multi-group analysis further revealed that the relationship between brand attributes and attitudes significantly differs across Chinese and US COOs where the path coefficient is stronger for elites' preference for Chinese brands. Originality/value: This study is the first of its kind to explore the COO effects on consumer cognitive structures. The findings contribute to MEC theory and shed light on the understanding towards elites' preference for foreign brands. [ABSTRACT FROM AUTHOR]

PhoP-PhoR, one of the 12 two-component systems (TCSs) that empower M. tuberculosis to sense and adapt to diverse environmental conditions, remains essential for virulence, and therefore, represents a major target to develop novel anti-TB therapies. Although both PhoP and PhoR have been structurally characterized, the signal(s) that this TCS responds to remains unknown. Here, we show that PhoR is a sensor of acidic pH/high salt conditions, which subsequently activate PhoP via phosphorylation. In keeping with this, transcriptomic data uncover that acidic pH- inducible expression of PhoP regulon is significantly inhibited in a PhoR-deleted M. tuberculosis. Strikingly, a set of PhoP regulon genes displayed a low pH-dependent activation even in the absence of PhoR, suggesting the presence of non-canonical mechanism(s) of PhoP activation. Using genome-wide interaction-based screening coupled with phosphorylation assays, we identify a non-canonical mechanism of PhoP phosphorylation by the sensor kinase PrrB. To investigate how level of P~PhoP is regulated, we discovered that in addition to its kinase activity PhoR functions as a phosphatase of P~PhoP. Our subsequent results identify the motif/residues responsible for kinase/phosphatase dual functioning of PhoR. Collectively, these results uncover that contrasting kinase and phosphatase functions of PhoR determine the homeostatic mechanism of regulation of intra-mycobacterial P~PhoP which controls the final output of the PhoP regulon. Together, these results connect PhoR to pH-dependent activation of PhoP with downstream functioning of the regulator. Thus, PhoR plays a central role in mycobacterial adaptation to low pH conditions within the host macrophage phagosome, and a PhoR-deleted M. tuberculosis remains significantly attenuated in macrophages and animal models. Author summary: Virulence-associated PhoP-PhoR of M. tuberculosis represents an attractive target to develop anti-tubercular therapy, but to date, the signal(s) that this regulatory system responds to remains unknown. We discovered that acidic pH and high salt conditions activate PhoP using a PhoR-dependent mechanism. Thus, pH inducible PhoP regulon expression is significantly impacted in a PhoR-depleted M. tuberculosis H37Rv. Our subsequent investigations reveal that homeostatic mechanism of regulation of P~PhoP relies on kinase/phosphatase dual functioning of PhoR, which determines mycobacterial pH homeostasis by controlling the final output of the PhoP regulon. Unexpectedly, global regulatory studies uncover that there can be PhoR-independent mechanism(s) of in vivo activation of PhoP. While probing for a non-canonical mechanism, we demonstrate that the sensor kinase (SK) PrrB phosphorylates PhoP. These results connect two SKs with signal-dependent activation of PhoP. [ABSTRACT FROM AUTHOR]

Acceptance sampling plans are commonly utilized for planning, process control, and implementation of industrial data sets. In addition to this, they also provide a solution for process quality control. They could be used for executing a decision for acceptance or rejection of a lot. A good acceptance sampling plan can be formulated depending on the requirements of the project. Usually, the plan should follow a defined lifetime distribution. Hence, the appropriate plan would not only determine the plan parameters but would also be cost and time efficient. In this article, an attribute multiple dependent repetitive group sampling (MDRGS) plan is developed assuming that the lifetime of the product follows the Marshall-Olkin logistic-exponential (MOLE) distribution. The parameters of plan are examined by considering a two-point approach. The suggested plan is contrasted with the single sampling and repeated group sampling plans. Finally, the implementation of the proposed plan is discussed using industrial as well as simulated data sets. It is concluded that the proposed plan reduces the sampling inspection cost and time as compared to existing acceptance sampling plans. [ABSTRACT FROM AUTHOR]

Background: Migraine is a typical cripple issue of the brain identified with cerebral pain which is an indication of numerous health conditions. About 18% of women (27 million) and 6% of men (10 million) are afflicted by migraine in the United States. Based on a case-control study, to explore the different risk factors, causing migraine in females and examine the association between risk factors and migraine. Methods: A sample of 1055 individuals were selected in different areas of Lahore from September 2019 to March 2020. The information was obtained by using the direct interview method and questionnaire method. Descriptive analysis, bivariate analysis and binary logistic regression analysis were carried out in data analysis. Results: Among 1055 individuals 740 cases and 315 controls were included. In a binary logistic regression model, physical activities, stress, summer season, menstruation and morning were the risk factors that cause migraine and these were found to be positively significant with the odds ratios and 95% confidence interval of odds ratios (1.399; 1.122–1.746), (1.510; 1.187–1.922), (1.595; 1.374–1.851), (1.513; 1.247–1.836) and (1.309; 1.028–1.665) respectively. Nausea, isolation and back head pain were caused by migraine and these were found positively significant with the odds ratios and 95% confidence interval of odds ratios(1.290; 1.122–1.484), (1.882; 1.617–2.190) and (1.285; 1.123–1.471) respectively. Conclusions: Stress, physical Activities and Menstruation increase the risk of migraine but weight loss, Breakfast, lunch, thirst, injury and Second trimester during pregnancy reduce the risk of migraine. [ABSTRACT FROM AUTHOR]

Objective: To compare the topical effects of lactobacillus acidophilus strain and topical antibiotics during the phase of re-epithelization in wound repair. Study Design: Experimental study. Setting: Al-Tibri Medical College, Isra University Karachi. Period: June to November 2022. Material & Methods: This study took place in in which 45 Wistar rats were acquired and divided into three groups, Group A the control group in which normal saline was applied, Group B in which topical Lactobacillus acidophilus was applied, and Group C in which topical neomycin was applied on the 3rd, 7th, and 14th day of the study. A subcutaneous incision was given on all the rats of equal proportion, and on the 3rd, 7th, and 14th day of sampling a histological section was acquired. A micrometer was used to measure the thickness of the dermis and epidermis. Data was analyzed using SPSS, with the p-value set at <0.05. Results: Significant difference was seen in the mean thickness of epidermis when Lactobacillus acidophilus groups was compared with both Group A and C on the 3rd, 7th, and 14th day of the study. Significant difference was also seen in the mean thickness of the dermis when Lactobacillus acidophilus was compared with both Group A and C on the 3rd, 7th, and 14th day of the study. Conclusion: Lactobacillus acidophilus plays a potent rote in repairing dermal tissue as it increased the thickness of dermis and epidermis. [ABSTRACT FROM AUTHOR]

The current work is one step in filling a large void in the research left by the advent of neutrosophic Statistics (NS), a philosophized variant of classical statistics (CS). The philosophy of NS deals with techniques for investigating data that is ambiguous, hazy, or uncertain. The traditional techniques of estimation utilizing auxiliary information work under specific determinate data, which in the case of neutrosophic data may lead to mistakes (over/ under-estimation). This study presents a generalized neutrosophic ratio-type exponential estimator (NRTEE) for estimating location parameters and achieving the lowest mean square error (MSE) possible for interval neutrosophic data (IND). The offered NRTEE helps to deal with the uncertainty and ambiguity of data. Unlike typical estimators, its findings are not single-valued but rather in interval form, which reduces the possibility of over-or under-estimation caused by single crisp outcomes and also increases the likelihood of the parameter dwelling in the interval. It improves the efficiency of the estimator since we have an estimated interval that contains the unknown value of the population mean with a minimal MSE. The suggested NRTEE's efficiency is further addressed by utilizing real-life IND of temperature and simulations. A comparison is also performed to establish the superiority of the proposed estimator over the traditional estimators. The limits are calculated and discussed in cases when our suggested estimator is always efficient. The suggested estimator is the most efficient of all estimators and outperformed all others on both IND and classical data. [ABSTRACT FROM AUTHOR]

Objective: To assess depression level in work force of a Teaching hospital. Study Design: Cross Sectional study. Setting: Al-Tibri Medical College and Hospital. Period: June 2021 to August 2021. Material & Methods: Total 250 faculty members of 7 different medical colleges and teaching hospital across the Sindh, Pakistan participates in the survey from 7 different medical colleges. Survey was conducted thorough online google form. Data was statistically analyzed by SPSS and Chi-square was performed to analyze the relationship between the professional environment and mental health. Results: It was observed that the 10% clinical faculty members and only 1% basic science faculty were statistically significant at p level p<0.005 and p<0.001 respectively. While other demographic factors were also found to be statistically significant at p<0.001. Conclusion: The results revealed the clinical faculty is at higher risk mental health issues then the faculty of the basic sciences. Since the clinical environment is to relate to the public dealing and handling or listening the traumatic cases on regular basis which might affect the mental health of the working personnel. [ABSTRACT FROM AUTHOR]

It is always foreseen to upturn the efficiency of an acceptance sampling plan for lot sentencing. In this research, variable multiple dependent state sampling plan considering the quality cost with rectifying inspection is proposed for normally distributed quality characteristics. The staple objective is to curb the total cost of the lot under inspection and improve the quality of outgoing lots. Tables are constructed for optimal plan parameters by increasing forgoing lots. The behavior of cost parameters on total cost has been investigated. Protection and cost curves are portrayed to show the efficacy of the proposed plan with rectifying single acceptance sampling plan using the cost model. Using the cost model, the proposed plan turns out to be more effectual than the single acceptance sampling plan in terms of sample size, average outgoing quality, and total cost. c i has emerged having a substantial effect on total cost trailed by c o and c f with the tiniest effect. Finally, an example is given to demonstrate the proposed plan. [ABSTRACT FROM AUTHOR]

Simple Summary: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung carcinoma (NSCLC). In our study, we analyzed 5259 total cases of PSC, illuminating demographic trends and outcomes related to different treatment strategies. PSC mostly affects Caucasian males between 70 and 79. Male gender and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes. The COSMIC analysis show the most common mutations in PSC are TP53, ARID1A, NF1, SMARCA4, and KMT2D. With this analysis, we hope to provide further data to better inform clinicians of effective treatment strategies for their patients. Background: Pulmonary sarcomatoid carcinoma (PSC) is a rare subtype of non-small cell lung cancer (NSCLC) with an aggressive clinical nature and poor prognosis. With novel targeted therapeutics being developed, new ways to effectively treat PSC are emerging. In this study, we analyze demographics, tumor characteristics, treatment modalities, and outcomes of PSC and genetic mutations in PSC. Methods: Data from the Surveillance, Epidemiology, and End Results (SEER) database were reviewed to analyze cases of pulmonary sarcomatoid carcinoma from 2000 to 2018. The molecular data with the most common mutations in PSC were extracted from the Catalogue Of Somatic Mutations in Cancer (COSMIC) database. Results: A total of 5259 patients with PSC were identified. Most patients were between 70 and 79 years of age (32.2%), male (59.1%), and Caucasian (83.7%). The male-to-female ratio was 1.45:1. Most tumors were between 1 and 7 cm in size (69.4%) and poorly differentiated (grade III) (72.9%). The overall 5-year survival was 15.6% (95% confidence interval (95% CI) = 14.4–16.9)), and the cause-specific 5-year survival was 19.7% (95% CI = 18.3–21.1). The five-year survival for those treated with each modality were as follows: chemotherapy, 19.9% (95% CI = 17.7–22.2); surgery, 41.7% (95% CI = 38.9–44.6); radiation, 19.1% (95% CI = 15.1–23.5); and multimodality therapy (surgery and chemoradiation), 24.8% (95% CI = 17.6–32.7). On multivariable analysis, age, male gender, distant stage, tumor size, bone metastasis, brain metastasis, and liver metastasis were associated with increased mortality, and chemotherapy and surgery were associated with reduced mortality (p < 0.001). The best survival outcomes were achieved with surgery. The most common mutations identified in COSMIC data were TP53 31%, ARID1A 23%, NF1 17%, SMARCA4 16%, and KMT2D 9%. Conclusions: PSC is a rare and aggressive subtype of NSCLC, usually affecting Caucasian males between 70 and 79. Male gender, older age, and distant spread were associated with poor clinical outcomes. Treatment with surgery was associated with better survival outcomes. [ABSTRACT FROM AUTHOR]

Primary non-Hodgkin's lymphoma of the bone is an unusual presentation of Hodgkin's lymphoma, with primary cranial vault lymphoma (PCVL) being the rarest of bone lymphomas. We describe a case of an immunocompetent elderly patient with new onset gait imbalance and cognitive delays. Brain imaging showed a large extra-axial mass with osseous invasion. An initial misdiagnosis of meningioma led to delays in management. Further work up included a brain magnetic resonance image showing a large right transcalvarial parietal mass. The mass was surgically removed, and pathology revealed B-cell lymphoma with low-grade features thus establishing the diagnosis of PCVL. Management included subtotal resection of the tumor followed by adjuvant radiation therapy. The patient has achieved a durable response for over a year. Meningioma and PCVL have similar imaging and clinical presentations. This case report addresses differing features of the tumors and explores therapeutic options for management of PCVL. [ABSTRACT FROM AUTHOR]

Ticks are ectoparasites that cause dermatologic reactions directly by their bites and indirectly as vectors of bacterial, protozoal and viral diseases. Consequences vary from minor local reactions to significant systemic sequelae and are therefore of clinical relevance to dermatologists. In this article, Australian ticks of medical importance are reviewed through the lens of dermatology. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) have various applications in the biomedical field and are considered excellent microbicidal agents. Moreover, biological synthesis of AgNPs using medicinal plants further improves the medicinal applicability of these plants. In this study, the aqueous extract of Alocasia odora rhizome (RE) and Alocasia odora stem (SE) were used to synthesize stem aqueous extract-AgNPs (SNP) and rhizome aqueous extract-AgNPs (RNP). Furthermore, RNP and SNP were evaluated for their virucidal potential. The synthesis of SNP and RNP was monitored using a UV spectrophotometer by observing their surface plasmon resonance peak. In addition, scanning electron microscopy (SEM) gave further insight into their morphology and particle size, whereas energy-dispersive X-ray spectroscopy (EDX) confirmed the presence of silver ions. Interestingly, Fourier-transform infrared spectroscopy (FTIR) analysis of AgNPs revealed that phytomolecules acted as capping and stabilizing agents for SNP and RNP. The in vitro cytotoxicity of SNP and RNP was further analyzed using MTT assay on the U87-MG human glioblastoma cancer cell line and SNP found to be the most cytotoxic (43.40 µg/ml) among all. Besides that, SNP has also found to show the maximum cytopathic effects (CPE) against dengue virus type 2 (DENV-2) on Huh-7 cell line. As a result of the observations, it can be concluded that they can become a promising antiviral drug candidate and thus merit further testing. Key points: • AgNPs were successfully synthesized through Alocasia odora aqueous extract. • AgNPs were more cytotoxic on the U87-MG cell line than the extract alone. • AgNPs have shown significant reduction in the dengue viral infection than the extract alone. [ABSTRACT FROM AUTHOR]

ICOS/ICOSL and CD28/B7-1/B7-2 are T cell co-stimulators and CTLA-4 is an immune checkpoint inhibitor that play critical roles in the pathogenesis of neoplasia. Chitinase 3-like-1 (CHI3L1) is induced in many cancers where it portends a poor prognosis and contributes to tumor metastasis. Here we demonstrate that CHI3L1 inhibits the expression of ICOS, ICOSL and CD28 while stimulating CTLA-4 and the B7 moieties in melanoma lung metastasis. We also demonstrate that RIG-like helicase innate immune activation augments T cell co-stimulation, inhibits CTLA-4 and suppresses pulmonary metastasis. At least additive antitumor responses were seen in melanoma lung metastasis treated with anti-CTLA-4 and anti-CHI3L1 antibodies in combination. Synergistic cytotoxic T cell-induced tumor cell death and the heightened induction of the tumor suppressor PTEN were seen in co-cultures of T and tumor cells treated with bispecific antibodies that target both CHI3L1 and CTLA-4. Thus, CHI3L1 contributes to pulmonary metastasis by inhibiting T cell co-stimulation and stimulating CTLA-4. The simultaneous targeting of CHI3L1 and the CTLA-4 axis with individual and, more powerfully with bispecific antibodies, represent promising therapeutic strategies for pulmonary metastasis. [ABSTRACT FROM AUTHOR]

In this article, we propose a generalized class of exponential type estimators for estimating the mean of delicate variable in the existence of non-sensitive two auxiliary variables. The performance of mean estimator is obtained by using generalized two stage optional randomized response model. The expression for the bias and the mean square error are obtained up to first degree of approximation. Certain special cases for the generalized class are discussed. An extensive simulation study is performed to determine the performance of the estimators. It is observed that the suggested class of estimators performs more efficiently than some existing estimators. [ABSTRACT FROM AUTHOR]

Microtubules have been an attractive target of cancer drug discovery due to their highly dynamic nature during mitosis. Griseofulvin, a natural antifungal compound, is known to interfere with microtubule dynamics. In the present study, we prepared and analyzed twenty‐seven novel griseofulvin derivatives. Three of these compounds had GI50 values <10 μM (5.74 to 9.7 μM) in breast cancer cell line CAL‐51. The most promising compound ((2S,6'R)‐4'‐(benzhydrylamino)‐7‐chloro‐4,6‐dimethoxy‐6'‐methyl‐3H‐spiro[benzofuran‐2,1'‐cyclohexan]‐3'‐ene‐2',3‐dione), was characterized as a microtubule‐stabilizing agent with a GI50 value of 5.74±1.43 μM compared to 10.79±3.06 μM GI50 for parental griseofulvin. It also inhibited the proliferation of other cancer cell lines, including KB‐3‐1 and HCT116, with GI50 values of 1.19±0.34 μM and 2.48±0.40 μM, respectively. Treatment of cancer cells with it resulted in aberrant mitosis causing G2/M arrest. Finally, we show that this compound increased the expression of p53 protein and induced apoptotic cell death. [ABSTRACT FROM AUTHOR]

Objective: To asses if Topical probiotics and steroids can accelerate the process of angiogenesis in wound repair. Study Design: Longitudinal Experimental study. Setting: Al-Tibri Medical College. Period: Jan 2020 to Dec 2020. Material & Methods: Total 72 male albino rats were acquired from the animal house of the institution, and 18 as a requirement of per day of sampling included 6 animals/gp. An equal size incision of (2x2cm2) was made in all the animals. Group A was given Topical Normal Saline (Control Group), Group B was given the Probiotic (Lactobacillus Acidophilus), and Group C was given Topical Steroid (Dexamethasone). Samples from the wound created surgically was obtained on the 3rd, 7th, 14th, and 21st Day and slides were created to observe the number of blood vessels formed and angiogenesis under a light microscope. Data was analyzed using SPSS version 21.0. To compare the mean between the groups, the ANOVA was applied along with post hoc Tukey's test. The level of significance was considered P≤0.05. Results: The mean number of blood vessels formed in Group A (Control Group) was 2.75, 4, 5.25, and 5.50, in Group B (Probiotics Group) was 10, 13.50, 2.25, and 1, and in Group C (Steroid Group) was 3.75, 5.50, 3, and 2.25 on the 3rd, 7th, 14th, and 21st Day respectively. Significant difference was seen in the mean number of blood vessels formed when the Probiotic group was compared to Group A and C. Conclusion: Topical Probiotic accelerates the process of angiogenesis in wound repair due to their anti-inflammatory response. [ABSTRACT FROM AUTHOR]

This observational study investigated the changes in choroidal thickness (ChT) in different patterns of diabetic macular edema (DME) based on image processing using enhanced-depth imaging spectral-domain optical coherence tomography (EDI-SD-OCT). Participants with ocular conditions affecting the fundus view, including retinal diseases, were excluded. After observing the patient's medical record, multicolor fundus photos, thickness maps, and subtypes of DME were diagnosed according to the criteria reported by the Early Treatment Diabetic Retinopathy Study (ETDRS). Edema was classified as focal or diffuse and was subdivided into cystic macular edema (CME), CME with subretinal fluid (CME+), and spongy macular edema (SME). Image processing was performed on the B-scan images from SD-OCT to segment the choroid layer and obtain the choroid thickness. A total of 159 eyes of 81 patients (46 males and 35 females; 57.53 ± 9.78 years of age), and 57 eyes of 30 healthy individuals (age 57.34 ± 8.76 years) were enrolled in this study. Out of 159 eyes, 76 had focal macular edema (FME), 13 exhibited SME, and 51 presented CME. Among those with cystic macular edema, 19 eyes showed subretinal fluid (CME+). The average choroidal thickness in FME, diffuse SME, CME, and CME+ was 216.95 ± 52.94 µm, 243.00 ± 46.34 µm, 221.38 ± 60.78 µm, and 249.63 ± 53.90 µm, respectively. The average choroidal thickness in age-matched controls was 213.88 ± 45.60 µm. Choroidal thickness increases with the severity of edema; choroidal thickness was higher in diffuse macular edema than in FME. However, choroidal thickness increased in cystic macular edema with subretinal fluid (CME+). [ABSTRACT FROM AUTHOR]

OBJECTIVE: To inspect the effects of naproxen sodium pre-operatively on the potency of Inferior alveolar nerve block in patients suffering from symptomatic irreversible pulpitis. METHODOLOGY: A cross-sectional study was conducted at Operative Department, Hamdard University Dental Hospital Karachi, from July 2018 to February 2019 using a non-probability consecutive sampling technique, including patients between 18-45 years of age. One hundred patients with symptomatic irreversible pulpitis in the posterior teeth of the mandible were randomly given 550 mg naproxen sodium or similar placebo capsules 60 minutes before the delivery of a conventional inferior alveolar nerve block. Patients having allergies, contraindications to naproxen sodium, pregnancy, lactating mothers, not giving consent, patients experiencing only mild pain (verified with Visual Analog scale) or taking pain medication in the last 6 hours were excluded. Fifteen minutes after the inferior alveolar nerve block delivery, sufficient lip numbness was confirmed, and endodontic therapy was commenced. Success determined if the subjects remained pain-free or showed mild pain (≤54mm on a 170mm Visual analog scale) on access or instrumentation. SPSS version 22 was utilized for data analysis. RESULTS: The success of the inferior alveolar nerve block demonstrated by the placebo group was 40%, and the experimental group was remarkably 98%. A substantial significant difference was evident between the two research groups. CONCLUSION: Variations in the two groups support that a significant rise in the success rate of the inferior alveolar nerve block was observed in subjects who consumed a pre-operative dose of 550 mg naproxen sodium with symptomatic irreversible pulpitis. [ABSTRACT FROM AUTHOR]

Background: Macular oedema is a final common pathway of a multitude of both ocular and systemic insults. This study was conducted to evaluate the short-term efficacy and safety of intraocular Ranibizumab in patients with macular oedema in a 'real-world' setting in Pakistan. Methods: A prospective multicenter study conducted at Amanat Eye Hospitals in Islamabad and Rawalpindi from 1st August 2018 to 1st November 2019. Forty-four eyes of 34 patients with macular oedema were treated with monthly intravitreal Ranibizumab (Patizra®) injections for three consecutive months. Best-corrected visual acuity (BCVA), and optical coherence tomography (OCT) parameters including central retinal thickness (CRT) and macular volume were assessed prior to the injections and then 4 weeks post the final injection and compared. Results: BCVA improved from logMAR 0.61±0.40 at baseline to 0.27±0.35 four weeks after the third intravitreal injection. CRT decreased from 428.54±187.06µm at baseline to 364.50±170.49 μm. Macular volume showed a non-significant decrease from 9.97±3.19 mm3 at baseline to 9.22±2.68 mm³ four weeks after the third intravitreal injection. No systemic or ocular complications were observed during the course of the study. Conclusion: Treatment with intravitreal Patizra® injections was found safe and resulted in clinically and statistically significant improvement in visual acuity and the SD-OCT parameter of central retinal thickness in patients with macular oedema secondary to various retinal pathologies. There was no significant decrease in the macular volume. [ABSTRACT FROM AUTHOR]

DNA damage is a causative factor in ageing of the vasculature and other organs. One of the most important vascular ageing features is reduced nitric oxide (NO)soluble guanylate cyclase (sGC)—cyclic guanosine monophosphate (cGMP) signaling. We hypothesized that the restoration of NO‐sGC‐cGMP signaling with an sGC activator (BAY 54–6544) may have beneficial effects on vascular ageing and premature death in DNA repair‐defective mice undergoing accelerated ageing. Eight weeks of treatment with a non‐pressor dosage of BAY 54–6544 restored the decreased in vivo microvascular cutaneous perfusion in progeroid Ercc1∆/− mice to the level of wild‐type mice. In addition, BAY 54–6544 increased survival of Ercc1∆/− mice. In isolated Ercc1∆/− aorta, the decreased endothelium‐independent vasodilation was restored after chronic BAY 54–6544 treatment. Senescence markers p16 and p21, and markers of inflammation, including Ccl2, Il6 in aorta and liver, and circulating IL‐6 and TNF‐α were increased in Ercc1∆/−, which was lowered by the treatment. Expression of antioxidant genes, including Cyb5r3 and Nqo1, was favorably changed by chronic BAY 54–6544 treatment. In summary, BAY 54–6544 treatment improved the vascular function and survival rates in mice with accelerated ageing, which may have implication in prolonging health span in progeria and normal ageing. [ABSTRACT FROM AUTHOR]

Monocytes are key players in innate immunity, with their ability to regulate inflammatory responses and combat invading pathogens. There is a growing body of evidence indicating that long non-coding RNA (lncRNA) participate in various cellular biological processes, including the innate immune response. The immunoregulatory properties of numerous lncRNAs discovered in monocytes remain largely unexplored. Here, by RNA sequencing, we identified a lncRNA JHDM1D-AS1, which was upregulated in blood monocytes obtained from patients with sepsis relative to healthy controls. JHDM1D-AS1 expression was induced in primary human monocytes exposed to Toll-like receptor ligands, such as lipopolysaccharide (LPS), or bacteria. The inducibility of JHDM1D-AS1 expression in monocytes depended, at least in part, on nuclear factor-kB activation. JHDM1D-AS1 knockdown experiments in human monocyte-derived macrophages revealed significantly enhanced expression of inflammatory mediators, before and after exposure to LPS, relative to control cells. Specifically, genes involved in inflammatory responses were upregulated (e.g., CXCL2, CXCL8, IL1RN, TREM1, TNF, and IL6), whereas genes involved in anti-inflammatory pathways were downregulated (e.g., SOCS1 and IL10RA). JHDM1D-AS1 overexpression in a pro-monocytic cell line revealed diminished pro-inflammatory responses subsequent to LPS challenge. Collectively, these findings identify JHDM1D-AS1 as a potential anti-inflammatory mediator induced in response to inflammatory stimuli. [ABSTRACT FROM AUTHOR]

This essay recounts the author's experience of growing up in a traditional Pakistani home, centered around a patriarchal culture in which men are the protectors and providers of the home and women are the caretakers. The reader is taken on a journey in which the writer moves to the United States, undergoes a drastic individuation process, and finds herself in a relationship with someone who embodies the shadow elements of the Dark Mother archetype. This relationship is crippling in many respects, and yet the writer triumphs by learning how to cook for herself—the alchemy of this act ultimately helps heal and nurture her soul as she finds her way back to Self. [ABSTRACT FROM AUTHOR]

The poor barrier of cellulosic paper against water vapor and oil limits its wide application as a packaging material. Lamination, extrusion, and dispersion coating are applied on paper surface to improve barrier properties. Dispersion coating can be applied to paper surface on line during paper preparation using rod coater. In the present study, an attempt has been made to increase the process speed of coating preparation by single-step process at varying pigment concentration. Coating dispersion was applied on kraft paper using laboratory rod coated and dried in hot air oven at 80°C for 5 min. Furthermore, thermal stability, water vapor barrier properties, and grease resistance of PVOH/kaolin and PVOH/talc-coated paper were studied. Additionally, the effect of single layer and bilayer coating on paper properties was also studied. Permeability model was used to predict the orientation of pigments to the surface of paper. Viscosity of both kaolin and talc-based dispersion increased with the increase in pigment concentration. Thermal studies showed that at 600°C residual mass (%) of PVOH film increased from 0.6 to 9.89% and 15% with the addition of 25% (by weight) kaolin and talc pigment. At high pigment concentration (40–50%, by weight), the highest reduction in WVTR was observed for both the pigments. Excellent coverage of paper surface and high grease resistance was observed for all coating formulations. Our study showed that talc provides better thermal and barrier properties to coated paper than kaolin. [ABSTRACT FROM AUTHOR]

Multiple sclerosis (MS) is a chronic and complex neurodegenerative disease, distinguished by the presence of lesions in the central nervous system (CNS) due to exacerbated immunological responses that inflict oligodendrocytes and the myelin sheath of axons. In recent years, studies have focused on targeted therapeutics for MS that emphasize the role of G protein-coupled receptors (GPCRs), specifically cannabinoids receptors. Clinical studies have suggested the therapeutic potential of cannabinoids derived from Cannabis sativa in relieving pain, tremors and spasticity. Cannabinoids also appear to prevent exaggerated immune responses in CNS due to compromised blood–brain barrier. Both, endocannabinoid system (ECS) modulators and cannabinoid ligands actively promote oligodendrocyte survival by regulating signaling, migration and myelination of nerve cells. The cannabinoid receptors 1 (CB1) and 2 (CB2) of ECS are the main ones in focus for therapeutic intervention of MS. Various CB1/CB2 receptors agonists have been experimentally studied which showed anti-inflammatory properties and are considered to be effective as potential therapeutics for MS. In this review, we focused on the exacerbated immune attack on nerve cells and the role of the cannabinoids and its interaction with the ECS in CNS during MS pathology. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the restoration of sperm motility with the antioxidant oils (Virgin coconut oil and Corn oil) therapy in Phenytoin induced testicular toxicity of rats. Study Design: Experimental Study. Setting: Al-Tibri Medical College and Hospital. Period: November 2019 to March 2020. Material & Methods: Forty-eight male albino rats weighing between 150-250gms were taken from the animal house of Al-Tibri medical college and placed in 4 groups, each with 12 rats. Group A was the control group receiving saline, Group B received Phenytoin only, Group C received Phenytoin and Virgin coconut oil, and Group D received Phenytoin and Corn oil. The rats were euthanized on the 4th, 5th, and 6th week of the study. Their epididymis was cut, and the epididymal fluid was placed under the microscope to determine sperm motility. Data was analyzed using SPSS Version 20.0 with one-way ANOVA followed with Post-Hoc Tukey’s test to compare statistical significance. Results: The significant difference was seen in mean % sperm motility when comparing Group B vs. A (≤0.001) and Group B vs. C (≤0.001) during the 4th, 5th, and 6th. Conclusion: Virgin Coconut Oil and Corn Oil both restored sperm motility. A higher percentage was observed in Virgin Coconut Oil received rats, which proved effective in resurging sperm motility. [ABSTRACT FROM AUTHOR]