Pichia pastoris Mediated Digestion of Water-Soluble Polysaccharides from Cress Seed Mucilage Produces Potent Antidiabetic Oligosaccharides.

Diabetes mellitus is a heterogeneous metabolic disorder that poses significant health and economic challenges across the globe. Polysaccharides, found abundantly in edible plants, hold promise for managing diabetes by reducing blood glucose levels (BGL) and insulin resistance. However, most of these polysaccharides cannot be digested or absorbed directly by the human body. Here we report the production of antidiabetic oligosaccharides from cress seed mucilage polysaccharides using yeast fermentation. The water-soluble polysaccharides extracted from cress seed mucilage were precipitated using 75% ethanol and fermented with Pichia pastoris for different time intervals. The digested saccharides were fractionated through gel permeation chromatography using a Bio Gel P-10 column. Structural analysis of the oligosaccharide fractions revealed the presence of galacturonic acid, rhamnose, glucuronic acid, glucose and arabinose. Oligosaccharide fractions exhibited the potential to inhibit α-amylase and α-glucosidase enzymes in a dose-dependent manner in vitro. The fraction DF73 exhibited strong inhibitory activity against α-amylase with IC50 values of 38.2 ± 1.12 µg/mL, compared to the positive control, acarbose, having an IC50 value of 29.18 ± 1.76 µg/mL. Similarly, DF72 and DF73 showed the highest inhibition of α-glucosidase, with IC50 values of 9.26 ± 2.68 and 50.47 ± 5.18 µg/mL, respectively. In in vivo assays in streptozotocin (STZ)-induced diabetic mice, these oligosaccharides significantly reduced BGL and improved lipid profiles compared to the reference drug metformin. Histopathological observations of mouse livers indicated the cytoprotective effects of these sugars. Taken together, our results suggest that oligosaccharides produced through microbial digestion of polysaccharides extracted from cress seed mucilage have the potential to reduce blood glucose levels, possibly through inhibition of carbohydrate-digesting enzymes and regulation of the various signaling pathways.

Artificial Intelligence and Machine Learning in Predicting the Response to Immunotherapy in Non-small Cell Lung Carcinoma: A Systematic Review.

Non-small cell lung carcinoma (NSCLC) is a prevalent and aggressive form of lung cancer, with a poor prognosis for metastatic disease. Immunotherapy, particularly immune checkpoint inhibitors (ICIs), has revolutionized the management of NSCLC, but response rates are highly variable. Identifying reliable predictive biomarkers is crucial to optimize patient selection and treatment outcomes. This systematic review aimed to evaluate the current state of artificial intelligence (AI) and machine learning (ML) applications in predicting the response to immunotherapy in NSCLC. A comprehensive literature search identified 19 studies that met the inclusion criteria. The studies employed diverse AI/ML techniques, including deep learning, artificial neural networks, support vector machines, and gradient boosting methods, applied to various data modalities such as medical imaging, genomic data, clinical variables, and immunohistochemical markers. Several studies demonstrated the ability of AI/ML models to accurately predict immunotherapy response, progression-free survival, and overall survival in NSCLC patients. However, challenges remain in data availability, quality, and interpretability of these models. Efforts have been made to develop interpretable AI/ML techniques, but further research is needed to improve transparency and explainability. Additionally, translating AI/ML models from research settings to clinical practice poses challenges related to regulatory approval, data privacy, and integration into existing healthcare systems. Nonetheless, the successful implementation of AI/ML models could enable personalized treatment strategies, improve treatment outcomes, and reduce unnecessary toxicities and healthcare costs associated with ineffective treatments.

Innate immune responses are increased in children with acute asthma exacerbation.

BACKGROUND: Little is known about the immune responses during acute asthma exacerbation. In this study, we examined immune responses in children following an acute asthma exacerbation. METHODS: We evaluated pro-inflammatory cytokine levels and gene expression profiles in blood samples from pediatric patients admitted for acute asthma exacerbation. Viral PCR was performed to differentiate between viral or non-viral-associated exacerbations. RESULTS: Following informed consent, clinical data were obtained from 20 children with asthma (median [interquartile range, IQR]: age 11.5 [8.0, 14.2]) years and 14 healthy age-matched controls (10.5 [7.0, 13.0]). Twelve had positive nasopharyngeal Polymerase chain reaction (PCR) for viral infection (11 rhinoviruses and 1 respiratory syncytial virus (RSV)). Nine were in the pediatric intensive care unit (PICU) and among them five required continuous positive airway pressure (CPAP). Mean (±SD) days on systemic steroids before drawing blood sample were 2.5 ± 1.6. Twelve had history of environmental allergies with 917 (274, 1396) IU/mL total IgE (median (IQR)). Compared with controls, IL-1RA and IL-10 levels were significantly increased and TNF-α significantly decreased in asthma subjects (p < .05 for all). RNA-seq analysis revealed 852 differentially expressed genes in subjects with asthma. Pathway analysis found upregulated genes and pathways involved in innate immune responses in subjects with asthma. Significantly reduced genes included pathways associated with T helper cell differentiation and activation. CONCLUSIONS: In acute asthma exacerbation, innate immune pathways remained increased while adaptive immune responses related to T helper cells are blunted and are independent of trigger or asthma severity. Our novel findings highlight the need to identify new therapies to target persistent innate immune responses to improve outcomes in acute asthma.

Examining feasibility, acceptability, and participant experiences of an anti-racist parenting intervention for White U.S. parents.

Many White parents engage in minimal discussion of race and racism with their children, instead engaging in color-evasive practices that communicate that race is unimportant and that White people are racially neutral. Even White parents who express a commitment to anti-racist parenting frequently struggle to act on this commitment and feel underprepared to do so. The current mixed methods pilot study focused on the feasibility, acceptability, and participant experiences of an intervention ("CounterACT") that aimed to address this gap in White U.S.-based parents' skills and knowledge. Participants in the study were 27 White U.S.-based parents of 4- to 6-year-old White children who completed pre- and postintervention surveys as well as postintervention interviews. Findings suggest that the CounterACT model was feasible and acceptable. Parent self-report further suggests that CounterACT had beneficial effects on parenting, parents' beliefs regarding White privilege, and children's critical reflection. Parents reported positive experiences of CounterACT, particularly group components of the intervention. Key elements of participants' experience included learning to understand their own and their children's experience of Whiteness; learning to better tolerate and regulate emotional discomfort; connecting with others for motivation, accountability, and learning; and approaching racial socialization with greater intentionality. However, parents also experienced limits in their progress toward anti-racist parenting. Many indicated a desire for more concrete guidance and greater support enacting what they were learning in their own parenting. A particular concern was how to discuss White racial identities effectively. Our discussion highlights the implications of these findings for future work in this area. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The prevalence, angiographic profile and clinical features, management, and outcomes of coronary artery perforation secondary to percutaneous coronary interventions in Pakistan: a retrospective cohort study.

Coronary artery perforation (CAP) is a rare entity that is often fatal. The mortality rates reported as high as up to 21% hence prompt diagnosis, intervention, and treatment are paramount to survival for such patients. Several factors may predispose a patient to coronary artery intervention including chronic total occlusion, severe calcification and tortuosity, aggressive use of oversized balloons and stents, and use of athero-ablative devices. Therefore, it is significant to have an insight related to it as despite being rare, it is one of the most feared complications of percutaneous coronary intervention (PCI). Method: We conducted a retrospective study of the patients who have undergone PCI at our institution from January 2015 to December 2021. During this duration, all the patients who had developed CAP based on angiographic review during the PCI were selected. The demographic, clinical, angiographic, procedure-related features, management of the CAP, and in-hospital and follow-up outcomes were gathered. Result: Thirty-five thousand fifty-nine patients underwent PCI among which, only 93 (0.26%) patients were complicated with (CAP. Fifty-eight (62.4%) patients were in the 50-70 years age range. The most common vessel involved was the left anterior descending (36.5%) followed by the right coronary artery (32.3%). The angiographic calcification was present in 51.6% of patients, significant tortuosity greater than 90° was seen in 48.4% of patients, chronic total occlusion was observed in 42% of patients and In-stent restenosis was found in 8.6% patients. The highest mortality of four patients was seen in the CAP involving the right coronary artery. Conclusion: Mostly the CAP involves large vessel perforations however both, the distal and large vessel perforations are related to the increased incidence of adverse clinical results which indicates the significance of the prevention and early identification and treatment of the perforation.

Effects of DNA methylase inhibitors in a murine model of severe BPD.

DNA methylation is necessary for developmental gene regulation, but adverse environments result in aberrant methylation and gene silencing. The current pilot study tested the hypothesis that treatment with DNA methylation inhibitors (decitabine; RG108) would improve alveolarization in a newborn murine model of severe bronchopulmonary dysplasia. Newborn mice exposed to maternal inflammation (LPS) and neonatal hyperoxia (85% O2) were treated with decitabine (p3, 0.1 mg/kg; p2, 4, 6, 0.1 mg/kg; or p2, 4, 6, 0.15 mg/kg) or RG108 (p3, 0.0013 mg/kg) delivered intranasally. Modest improvements in alveolarization were observed with decitabine, but no differences were observed with RG108. Attenuated phospho-SMAD2/3 levels and greater surfactant protein C protein levels compared to vehicle were observed with some tested doses. No detrimental side effects were observed with the doses used in this study. In summary, our pilot investigations identified a safe dose for intranasal administration of both methylation inhibitors and provides a foundation for further studies into methylation inhibitors in the context of neonatal lung injury.

Smartphone co-aided cobalt blue anterior segment with intraocular lens photography.

In this report, we have utilized a smartphone-based innovative tool named anterior segment photography with an intraocular lens (ASPI) with a cobalt blue filter on the smartphone flash for photographing fluorescein-stained corneas. An intraocular lens along with a cobalt blue filter was attached to the smartphone camera to achieve this purpose. The filter could block out all wavelengths of light except the blue wavelength (450-490 nm) emerging from the smartphone camera. A pilot study was conducted on 27 eyes of 25 patients where images of various corneal pathologies were obtained using ASPI blue light imaging. The images were clear and highly magnified and could be used for documentation, teleconsultation for expert opinion, education, and monitoring of disease progression. ASPI-aided blue light imaging could be easily fabricated and is a frugal inexpensive device, which is used by different ophthalmic personnel to obtain fluorescein-stained corneal images.

Impact of elexacaftor-tezacaftor-ivacaftor on bacterial colonization and inflammatory responses in cystic fibrosis.

BACKGROUND: Cystic fibrosis (CF) is a multisystem disease with progressive deterioration. Recently, CF transmembrane conductance regulator (CFTR) modulator therapies were introduced that repair underlying protein defects. Objective of this study was to determine the impact of elexacaftor-tezacaftor-ivacaftor (ETI) on clinical parameters and inflammatory responses in people with CF (pwCF). METHODS: Lung function (FEV1 ), body mass index (BMI) and microbiologic data were collected at initiation and 3-month intervals for 1 year. Blood was analyzed at baseline and 6 months for cytokines and immune cell populations via flow cytometry and compared to non-CF controls. RESULTS: Sample size was 48 pwCF, 28 (58.3%) males with a mean age of 28.8 ± 10.7 years. Significant increases in %predicted FEV1 and BMI were observed through 6 months of ETI therapy with no change thereafter. Changes in FEV1 and BMI at 3 months were significantly correlated (r = 57.2, p < 0.01). There were significant reductions in Pseudomonas and Staphylococcus positivity (percent of total samples) in pwCF through 12 months of ETI treatment. Healthy controls (n = 20) had significantly lower levels of circulating neutrophils, interleukin (IL)-6, IL-8, and IL-17A and higher levels of IL-13 compared to pwCF at baseline (n = 48). After 6 months of ETI, pwCF had significant decreases in IL-8, IL-6, and IL-17A levels and normalization of peripheral blood immune cell composition. CONCLUSIONS: In pwCF, ETI significantly improved clinical outcomes, reduced systemic pro-inflammatory cytokines, and restored circulating immune cell composition after 6 months of therapy.

Loss of Jagged1 in mature endothelial cells causes vascular dysfunction with alterations in smooth muscle phenotypes.

BACKGROUND: Notch signaling is an evolutionarily conserved pathway that functions via direct cell-cell contact. The Notch ligand Jagged1 (Jag1) has been extensively studied in vascular development, particularly for its role in smooth muscle cell maturation. Endothelial cell-expressed Jag1 is essential for blood vessel formation by signaling to nascent vascular smooth muscle cells and promoting their differentiation. Given the established importance of Jag1 in endothelial cell/smooth muscle crosstalk during development, we sought to determine the extent of this communication in the adult vasculature for blood vessel function and homeostasis. METHODS: We conditionally deleted Jag1 in endothelial cells of adult mice and examined the phenotypic consequences on smooth muscle cells of the vasculature. RESULTS: Our results show that genetic loss of Jag1 in endothelial cells has a significant impact on Notch signaling and vascular smooth muscle function in mature blood vessels. Endothelial cell-specific deletion of Jag1 causes a concomitant loss of JAG1 and NOTCH3 expression in vascular smooth muscle cells, resulting in a transition to a less differentiated state. Aortic vascular smooth muscle cells isolated from the endothelial cell-specific Jag1 deficient mice retain an altered phenotype in culture with fixed changes in gene expression and reduced Notch signaling. Utilizing comparative RNA-sequence analysis, we found that Jag1 deficiency preferentially affects extracellular matrix and adhesion protein gene expression. Vasoreactivity studies revealed a reduced contractile response and impaired agonist-induced relaxation in endothelial cell Jag1-deficient aortas compared to controls. CONCLUSIONS: These data are the first to demonstrate that Jag1 in adult endothelial cells is required for the regulation and homeostasis of smooth muscle cell function in arterial vessels partially through the autoregulation of Notch signaling and cell matrix/adhesion components in smooth muscle cells.

An exceptional biallelic N-terminal frame shift mutation in ZMPSTE24 leads to non-lethal progeria due to possible utilization of a downstream alternative start codon.

Biallelic mutations in ZMPSTE24 are known to be associated with autosomal recessive mandibuloacral dysplasia with type B lipodystrophy (MADB) and lethal restrictive dermopathy (RD), respectively. Disease manifestation is depending on the remaining enzyme activity of the mutated ZMPSTE24 protein. To date, complete loss of function has exclusively been reported in RD cases. In this study, we identified a novel N-terminal homozygous frameshift mutation (c.28_29insA) in a consanguineous family segregating with MADB. An in-depth analysis of the mutated sequence revealed, that the one base pair insertion creates a novel downstream in-frame start codon, which supposedly serves as an alternative translation initiation site (TIS). This possible rescue mechanism would explain the relatively mild clinical outcome in the studied individuals. Our findings demonstrate the necessity for careful interpretation of N-terminal variants potentially effecting translation initiation.

Chronic Allergen Challenge Induces Corticosteroid Insensitivity With Persistent Airway Remodeling and Type 2 Inflammation.

Type 2-high severe asthma is described as a distinct endotype with Th2 inflammation, high eosinophil lung infiltration, impaired lung function, and reduced corticosteroid sensitivity. While the inflammatory milieu is similar to mild asthma, patients with type 2-high severe asthma likely have underlying mechanisms that sustain asthma pathophysiology despite corticosteroid treatments. Acute and chronic allergen models induce robust type 2 inflammatory responses, however differences in corticosteroid sensitivity remains poorly understood. In the present study, we sensitized and challenged mice with ovalbumin (OVA; acute model) or mixed allergens (MA; chronic model). Corticosteroid sensitivity was assessed by administering vehicle, 1, or 3 mg/kg fluticasone propionate (FP) and examining key asthmatic features such as airway inflammation, remodeling, hyperresponsiveness, and antioxidant capacity. Both acute and chronic allergen exposure exhibited enhanced AHR, immune cell infiltration, airway inflammation, and remodeling, but corticosteroids were unable to fully alleviate inflammation, AHR, and airway smooth muscle mass in MA-challenged mice. While there were no differences in antioxidant capacity, persistent IL-4+ Th2 cell population suggests the MA model induces type 2 inflammation that is insensitive to corticosteroids. Our data indicate that chronic allergen exposure is associated with more persistent type 2 immune responses and corticosteroid insensitivity. Understanding differences between acute and chronic allergen models could unlock underlying mechanisms related to type 2-high severe asthma.

PRMT5 in T Cells Drives Th17 Responses, Mixed Granulocytic Inflammation, and Severe Allergic Airway Inflammation.

Severe asthma is characterized by steroid insensitivity and poor symptom control and is responsible for most asthma-related hospital costs. Therapeutic options remain limited, in part due to limited understanding of mechanisms driving severe asthma. Increased arginine methylation, catalyzed by protein arginine methyltransferases (PRMTs), is increased in human asthmatic lungs. In this study, we show that PRMT5 drives allergic airway inflammation in a mouse model reproducing multiple aspects of human severe asthma. We find that PRMT5 is required in CD4+ T cells for chronic steroid-insensitive severe lung inflammation, with selective T cell deletion of PRMT5 robustly suppressing eosinophilic and neutrophilic lung inflammation, pathology, airway remodeling, and hyperresponsiveness. Mechanistically, we observed high pulmonary sterol metabolic activity, retinoic acid-related orphan receptor γt (RORγt), and Th17 responses, with PRMT5-dependent increases in RORγt's agonist desmosterol. Our work demonstrates that T cell PRMT5 drives severe allergic lung inflammation and has potential implications for the pathogenesis and therapeutic targeting of severe asthma.

Randomized Controlled Trial of Omega-3 and -6 Fatty Acid Supplementation to Reduce Inflammatory Markers in Children with Autism Spectrum Disorder.

This double-blind, randomized controlled trial, tested fatty acid (FA) supplementation in children (ages 2- < 6 years) recently diagnosed with Autism Spectrum Disorder (ASD). Participants received daily oral FA supplement containing omega-3 and omega-6 FA, or a placebo for 90 days based on participant weight. Erythrocyte FAs and the cytokines, IL-1ß, IL-2, IFNγ, were measured in plasma obtained from serial blood collections. Treatment increased omega-3 and omega-6 FA levels (1.40 mol% for EPA and 1.62 mol% for DHA) and reduced IL-2 levels compared to placebo (- 0.17 pg/mL, 95% CI - 0.31, - 0.02, d = - 0.62). Omega 3-6 treatment was tolerable and adherence was greater than 70%. Future research will assess the effects of Omega 3-6 treatment on ASD symptoms. Registered on 06/08/2018 with ClinicalTrials.gov: NCT03550209.

A cross-sectional survey among parents to report challenges and barriers in the administration of medicines to children in United Arab Emirates.

Background: Lack of knowledge among parents can result in inappropriate administration practices.  After analyzing different studies among children, there was no data on challenges and barriers in the administration of drugs among children in this region because of the diverse environmental issues and challenges in the UAE. The objective of this study was to determine the reported administration practices of parents and challenges and barriers in the administration of drugs among children in UAE. Methods: A questionnaire-based survey was conducted. A convenience sampling technique was used to collect the data. An online Raosoft® sample size calculator was applied (n = 248). The inclusion criteria were parents who had a child under 10 years of age and gave consent to participate in this study. Children with vision problems, cognitive/physical disabilities, and caregivers other than parents were excluded from this study. Results: The study reported response rate of 73.2%. The mean ± S.D age of the parents in years was 35.5 ± 7.8, and the mean ± S.D of children aged years was 2.60 ± 1.54. The majority of parents (83.9%) completing the survey were mothers and resided in the city (97.2%). When the children did not like taking tablet drugs 41.9% used multiple practices and 26.2% of parents reported treatment failure due to oral drug administration. Around 47.6% of those who were interviewed reported that their children had swallowing problems during the administration of oral medication. A total of 22.2% of parents reported that they gave drugs in doses higher than prescribed by the doctor to treat their children more quickly. Similarly, a total of 64.5% of the parents reported self-medication without consultation from a healthcare provider. Conclusions: The study concluded that there were inappropriate drug administration practices among parents. Parents reported administration of higher doses to treat their children quickly.

Higher-Dose DHA Supplementation Modulates Immune Responses in Pregnancy and Is Associated with Decreased Preterm Birth.

Pregnancy and parturition involve extensive changes in the maternal immune system. In our randomized, multi-site, double-blind superiority trial using a Bayesian adaptive design, we demonstrated that 1000 mg/day of docosahexaenoic acid (DHA) was superior to 200 mg/day in preventing both early preterm birth (less than 34 weeks' gestation) and preterm birth (less than 37 weeks' gestation). The goal of this secondary study is to compare the effects of 1000 mg/day versus 200 mg/day on maternal inflammation, a possible mechanism by which DHA may prevent preterm birth. Maternal blood samples were collected at enrollment (12-20 weeks' gestation) and at delivery. Red blood cell DHA levels were measured by gas chromatography, and plasma concentrations of sRAGE, IL-6, IL-1ß, TNFα, and INFγ were measured by ELISA. Data were analyzed for associations with the DHA dose, gestational age at birth, and preterm birth (<37 weeks). Higher baseline and lower delivery levels of maternal sRAGE were associated with a greater probability of longer gestation and delivery at term gestation. Higher-dose DHA supplementation increased the probability of a smaller decrease in delivery sRAGE levels. Higher IL-6 concentrations at delivery were associated with the probability of delivering after 37 weeks, and higher-dose DHA supplementation increased the probability of greater increases in IL-6 concentrations between enrollment and delivery. These data provide a proposed mechanistic explanation of how a higher dose of DHA during pregnancy provides immunomodulatory regulation in the initiation of parturition by influencing sRAGE and IL-6 levels, which may explain its ability to reduce the risk of preterm birth.

Model-Independent Simulation Complexity of Complex Quantum Dynamics.

We present a model-independent measure of dynamical complexity based on simulation of complex quantum dynamics using stroboscopic Markovian dynamics. Tools from classical signal processing enable us to infer the Hilbert space dimension of the complex quantum system evolving under a time-independent Hamiltonian via pulsed interrogation. We illustrate this using simulated third-order pump-probe spectroscopy data for exciton transport in a toy model of a coupled dimer with vibrational levels, revealing the dimension of the singly excited manifold of the dimer. Finally, we probe the complexity of excitonic transport in light harvesting 2 (LH2) and Fenna-Matthews-Olson (FMO) complexes using data from two recent nonlinear ultrafast optical spectroscopy experiments. For the latter we make model-independent inferences that are commensurate with model-specific ones, including the estimation of the fewest number of parameters needed to fit the experimental data and identifying the spatial extent, i.e., delocalization size, of quantum states participating in this complex quantum dynamics.

To assess students' perception about Kahoot! as an innovative learning tool in oral pathology- a qualitative study.

This qualitative study was conducted to investigate the perception of third-year dental students' about Kahoot! as an innovative learning, teaching, and assessment tool for the subject of Oral Pathology at the Fatima Jinnah Dental College, Karachi. This online App was implemented as a teaching and assessment tool in both the first and second semesters during the academic year 2019. Out of 75 students, 50 were females and 25 were males. Students' opinion about Kahoot! was assessed using a questionnaire with a 5-point Likert scale. Kahoot! has been implemented for the first time in the dental curriculum of our institution. Around 90% of the students accepted that they can easily comprehend the knowledge, challenge their mental ability, and become an attentive learner. The quizzes assisted students to identify different oral structures, histological features, and oral mucosal alteration in an interesting way. According to students' opinion, Kahoot! assist them to develop a notion of self-directed learning (69; 92%), and prepared to attempt exams confidently (68; 90%).

Differences in symptoms and presentation delay times in myocardial infarction patients with and without diabetes: A cross-sectional study in Pakistan.

OBJECTIVE: A short pre-hospital delay, from the onset of symptoms to rapid initiation of reperfusion therapy, is a crucial factor in determining prognosis of myocardial infarction (MI). The purpose of this study was to evaluate symptoms and presentation delay times in MI patients with and without diabetes. METHODS: This cross-sectional study was conducted in 3 tertiary care hospitals of Pakistan over a period of 6 months. The study sample consisted of 280 consenting individuals diagnosed with ST-elevation MI (STEMI) or Non-ST elevation MI (NSTEMI), out of which 130 were diabetic and 150 were non-diabetic. Data was collected using a standardized questionnaire, investigating MI symptoms along with causes and duration of pre-hospital delay within 72hours of admission. RESULTS: No significant difference was found in the intensity of chest pain between diabetics and non-diabetics. Atypical symptoms of MI such as anxiety (p<0.001), cold sweats (p=0.034) and epigastric pain (p=0.017) were more frequently reported in diabetics. MI patients with diabetes had a significantly longer presentation delay time with 75% of the patients presenting after elapse of 3h. Only a few patients reported to the hospital within an hour of onset of symptoms (n=23, 8.2%), out of which majority were non-diabetics (n=18). A majority of patients (n=146, 52%) in both groups did not use emergency medical services. CONCLUSION: This study provides an incentive for further research, aiming to reduce pre hospital delay along with investigating the effectiveness of emergency medical services.

Is the dental clinical learning environment suitable? A survey of Khyber Pakhtunkhwa, Pakistan.

OBJECTIVE: To assess the clinical learning environment in dental institutes of Khyber Pakhtunkhwa. METHODS: The multi-centre cross-sectional survey was conducted from January to May 2017, and comprised students of three institutes affiliated with three different universities in Khyber Pakhtunkhwa province of Pakistan. These included the public-sector Khyber Medical University and two in the private sector: Gandhara University and Riphah International University. A validated Dental Clinical Learning Environment Instrument was distributed among the undergraduate and postgraduate students who were asked to record their perceptions using a six-item Likert scale. Data was analysed using non-parametric statistics. RESULTS: Of the 700 students approached, 553(79%) responded. Of them, 345(62.4%) were females. The mean score for the public-sector institute was 56.69% ± 26.88 (moderate) and 60.53% ± 27.94 (borderline-good) and 62.76% ± 26.02 (borderline-good) for the two private institutes respectively. Clinical teachers were significantly more approachable in private than public sector (p<0.05). The participants from public-sector institute reported lack of vigour, infrastructure, clinical resources and research opportunities. Those from the private sector felt more satisfied and confident about their clinical training but reported having patients for their appointments as a challenge. There were significant differences among those having different gender and levels of training (p<0.05). All participants found clinical seminars helpful. CONCLUSIONS: Clinical learning environment was slightly positive than negative but borderline. The students from private institutes had higher satisfaction than those in public..

Roles of UVA radiation and DNA damage responses in melanoma pathogenesis.

The growing incidence of melanoma is a serious public health issue that merits a thorough understanding of potential causative risk factors, which includes exposure to ultraviolet radiation (UVR). Though UVR has been classified as a complete carcinogen and has long been recognized for its ability to damage genomic DNA through both direct and indirect means, the precise mechanisms by which the UVA and UVB components of UVR contribute to the pathogenesis of melanoma have not been clearly defined. In this review, we therefore highlight recent studies that have addressed roles for UVA radiation in the generation of DNA damage and in modulating the subsequent cellular responses to DNA damage in melanocytes, which are the cell type that gives rise to melanoma. Recent research suggests that UVA not only contributes to the direct formation of DNA lesions but also impairs the removal of UV photoproducts from genomic DNA through oxidation and damage to DNA repair proteins. Moreover, the melanocyte microenvironment within the epidermis of the skin is also expected to impact melanomagenesis, and we therefore discuss several paracrine signaling pathways that have been shown to impact the DNA damage response in UV-irradiated melanocytes. Lastly, we examine how alterations to the immune microenvironment by UVA-associated DNA damage responses may contribute to melanoma development. Thus, there appear to be multiple avenues by which UVA may elevate the risk of melanoma. Protective strategies against excess exposure to UVA wavelengths of light therefore have the potential to decrease the incidence of melanoma. Environ. Mol. Mutagen. 59:438-460, 2018. © 2018 Wiley Periodicals, Inc.