Secoisolariciresinol diglucoside lignan concentrate of flaxseeds exhibits chemoprotective role in non-melanoma skin cancer through inhibition of CDK4 and upregulation of p53

Cyclin-dependent kinases (CDKs) serve as target for various cancers including skin cancer. Secoisolariciresinoldiglucoside (SDG) and lignans exert anticancer effect on colon cancer through inhibition of CDKs. However, reports of SDG lignan concentrate (SLC) of Linum usitatissimum (L.) on skin cancer are not available. Hence, in this study, we evaluated the effect of SLC of L. usitatissimum on skin cancer, and determined the mechanism of action. Cell viability studies were done using the A-375 cell line. Skin cancer was induced by dimethyl Benz(a) anthracene and croton oil in female balb/c mice. SLC (5%) was administered from the 7th to 16th week after which we evaluated serum and tissue parameters. The IC50 value of SLC was found to be 93.7 μg/mL on the A-375 cell line. Skin cancer control animals exhibited increased tumor volume and burden and an increase in non-specific serum markers and tissue markers. Treatment with SLC decreased tumor volume and burden, and serum and tissue markers. Histopathological studies also depicted protection with SLC treatment. Docking studies revealed that SDG exhibits a good binding score with CDK4. Skin cancer control mice showed significantly increased CDK4 mRNA and decreased p53 mRNA levels which were prevented by SLC treatment. SLC exhibited a chemopreventive effect in skin cancer depicted by a reduction in serum biomarker, oxidative stress, collagen levels, tumor volume, tumor burden, and histopathological studies. These effects are mediated through the inhibition of CDK4 and upregulation of p53

Secoisolariciresinol diglucoside lignan concentrate of flaxseeds exhibits chemoprotective role in non-melanoma skin cancer through inhibition of CDK4 and upregulation of p53

688-696Cyclin-dependent kinases (CDKs) serve as target for various cancers including skin cancer. Secoisolariciresinoldiglucoside (SDG) and lignans exert anticancer effect on colon cancer through inhibition of CDKs. However, reports of SDG lignan concentrate (SLC) of Linum usitatissimum (L.) on skin cancer are not available. Hence, in this study, we evaluated the effect of SLC of L. usitatissimum on skin cancer, and determined the mechanism of action. Cell viability studies were done using the A-375 cell line. Skin cancer was induced by dimethyl Benz(a) anthracene and croton oil in female balb/c mice. SLC (5%) was administered from the 7th to 16th week after which we evaluated serum and tissue parameters. The IC50 value of SLC was found to be 93.7 μg/mL on the A-375 cell line. Skin cancer control animals exhibited increased tumor volume and burden and an increase in non-specific serum markers and tissue markers. Treatment with SLC decreased tumor volume and burden, and serum and tissue markers. Histopathological studies also depicted protection with SLC treatment. Docking studies revealed that SDG exhibits a good binding score with CDK4. Skin cancer control mice showed significantly increased CDK4 mRNA and decreased p53 mRNA levels which were prevented by SLC treatment. SLC exhibited a chemopreventive effect in skin cancer depicted by a reduction in serum biomarker, oxidative stress, collagen levels, tumor volume, tumor burden, and histopathological studies. These effects are mediated through the inhibition of CDK4 and upregulation of p53

A study of clinicoradiological and functional outcomes of intramedullary nailing in diaphyseal radius ulna fractures

Background: The aim of this study was to evaluate the results of intramedullary nailing in diaphyseal fractures of radius and ulna in age group of 10 to 49 years and to understand its clinicoradiological and functional results.Methods: This is a retrospective case series study of forearm bone fractures and the selected management for the same over a period of 3 years. We chose the cases in which intramedullary nailing was the treatment modality which were followed up over a period of minimum 6 months. Patients with galeazzi variety, monteggia variety, pathological fracture or non-union after previous surgery were excluded. The outcomes were then evaluated with disabilities of the arm, shoulder and hand (DASH) score, Green and O’Brien score, and Grace and Eversmann functional outcome score.Results: Of the 22 patients, 10 patients had excellent functional outcome according to Grace and Eversmann score, 7 patients had good outcome, 4 patients had acceptable while 1 was unacceptable. Green and O’Brien also had similar results, except that patients among fair category were 3 and poor category were 3. The mean DASH score was 16.2.Conclusions: This study shows that closed method for fixation by intramedullary nailing of both bone forearm fractures leads to excellent to good functional outcomes (according to DASH score, Green and O Brien, and Grace and Eversmann score) with less complications. In 6 months follow up x ray there is radiological union in all cases with no angulation, malunion or non-union.

A prospective study of 50 cases of patella fractures treated with different modalities

Background: Fractures of patella account for 1% of all skeletal injuries. There is no universal accepted treatment for patellar fractures. After a fracture of the patella, the best results are obtained by accurate reduction and stable internal fixation. Partial or total patellectomy is generally indicated when the patella is so severely comminuted that an accurate reduction and reconstruction of the retropatellar joint surface cannot be achieved.Methods: The prospective study of 50 cases of patellar fractures was carried out at the department of orthopaedics for the period from May 2015 to December 2017. The maximum period of follow up was 18 months with a minimum period of follow up of 5 months (average 11.68 months). Operative treatment was done in patella fractures for more than 2 mm of articular displacement or 3 mm of fragment separation. Surgical options includes internal fixation with tension band wiring with k wire and partial patellectomy with extensor mechanism repair.Results: We have studied 50 patients where 7 cases were treated conservatively. In the present series 22 patients were treated with internal fixation out of which 13 patients had excellent results. 6 patients had good results. 21 patients were treated with partial patellectomy where 6 patients had excellent results, 11 patients had good and 4 patients had fair results.Conclusions: Patella should be preserved and Osteosynthesis whenever possible has better chance for excellent results. A good surgical technique, optimal operation room environment and judicious use of antibiotics will reduce the possibility of infection

Retinopathy predicts progression of fasting plasma glucose: An Early Diabetes Intervention Program (EDIP) analysis

Background Retinopathy is increasingly recognized in prediabetic populations, and may herald increased risk of metabolic worsening. The Early Diabetes Intervention Program (EDIP) evaluated worsening of glycemia in screen-detected Type 2 diabetes, following participants for up to 5 years. Here we have evaluated whether the presence of retinopathy at the time of detection of diabetes was associated with accelerated progression of glycemia. Methods We prospectively studied 194 participants from EDIP with available baseline retinal photographs. Retinopathy was determined at baseline using 7-field fundus photography and defined as an Early Treatment of Diabetic Retinopathy Study Scale grading score of ≥ 20. Results At baseline, 12% of participants had classical retinal lesions indicating retinopathy. In univariate Cox proportional hazard analysis, the presence of retinopathy at baseline was associated with a doubled risk of progression of fasting plasma glucose (HR 2.02; 95% CI 1.05–3.89). The retinopathy effect was robust to individual adjustment for age and glucose, the most potent determinants of progression in EDIP. Conclusion Retinopathy was associated with increased risk of progression of fasting plasma glucose among adults with screen-detected, early diabetes. Early detection of retinopathy may help individualize more aggressive therapy to prevent progressive metabolic worsening in early diabetes

Design and development of the ‘POD Adventures’ smartphone game: a blended problem-solving intervention for adolescent mental health in India

Introduction: Digital technology platforms offer unparalleled opportunities to reach vulnerable adolescents at scale and overcome many barriers that exist around conventional service provision. This paper describes the design and development of POD Adventures, a blended problem-solving game-based intervention for adolescents with or at risk of anxiety, depression and conduct difficulties in India. This intervention was developed as part of the PRemIum for ADolEscents (PRIDE) research programme, which aims to establish a suite of transdiagnostic psychological interventions organised around a stepped care system in Indian secondary schools. Methods and materials: Intervention development followed a person-centered approach consisting of four iterative activities: (i) review of recent context-specific evidence on mental health needs and preferences for the target population of school-going Indian adolescents, including a multiple stakeholder analysis of school counselling priorities and pilot studies of a brief problem-solving intervention; (ii) new focus group discussions with N=46 student participants and N=8 service providers; (iii) co-design workshops with N=22 student participants and N=8 service providers; and (iv) user-testing with N=50 student participants. Participants were aged 12-17 years and recruited from local schools in New Delhi and Goa, including a subgroup with self-identified mental health needs (N=6). Results: Formative data from existing primary sources, new focus groups and co-design workshops supported a blended format for delivering a brief problem-solving intervention, with counsellors supporting use of a game-based app on ‘offline’ smartphones. User-testing with prototypes identified a need for simplification of language, use of concrete examples of concepts and practice elements to enhance engagement. There were also indications that participants most valued relatability and interactivity within real-world stories with judicious support from an in-app guide. The final prototype comprised a set of interactive and gamified vignettes and a structured set of problem-solving questions to consolidate and generalise learning while encouraging real-world application. Discussion: Findings shaped the design of POD Adventures and its delivery as an open-access blended intervention for secondary school students with a felt need for psychological support, consistent with an early intervention paradigm. A randomised controlled trial is planned to evaluate processes and impacts of POD Adventures when delivered for help-seeking students in low-resource school settings

Profound defects in β-cell function in screen-detected type 2 diabetes are not improved with glucose-lowering treatment in the Early Diabetes Intervention Program (EDIP)

BACKGROUND: Few studies have measured the ability of interventions to affect declining β-cell function in screen-detected type 2 diabetes. The Early Diabetes Intervention Programme (ClinicalTrials.gov NCT01470937) was a randomized study based on the hypothesis that improving postprandial glucose excursions with acarbose would slow the progression of fasting hyperglycaemia in screen-detected type 2 diabetes. In the Early Diabetes Intervention Programme, the effect of acarbose plus lifestyle advice on progression of fasting hyperglycaemia over a 5-year period was not greater than that of placebo. However, there was an early glucose-lowering effect of the trial. The objective of the current secondary analysis was to describe β-cell function changes in response to glucose lowering. METHODS: Participants were overweight adult subjects with screen-detected type 2 diabetes. β-cell function was measured using hyperglycaemic clamps and oral glucose tolerance testing. The primary outcome was the change in β-cell function from baseline to year 1, the time point where the maximal glucose-lowering effect was seen. RESULTS: At baseline, participants exhibited markedly impaired first-phase insulin response. Despite significant reductions in weight, fasting plasma glucose (PG) and 2-h PG, there was no clinically significant improvement in the first-phase insulin response. Late-phase insulin responses declined despite beneficial glycaemic effects of interventions. CONCLUSIONS: Insulin secretion is already severely impaired in early, screen-detected type 2 diabetes. Effective glucose-lowering intervention with acarbose was not sufficient to improve insulin secretion or halt the decline of β-cell function

Walking and Calcified Atherosclerotic Plaque in the Coronary ArteriesHighlights: The National Heart, Lung, and Blood Institute Family Heart Study

Studies have reported mixed findings on the association between physical activity and subclinical atherosclerosis. We sought to examine whether walking is associated with prevalent coronary artery calcification (CAC) and aortic calcification (AC)

Towards Accurate Differential Diagnosis with Large Language Models

An accurate differential diagnosis (DDx) is a cornerstone of medical care, often reached through an iterative process of interpretation that combines clinical history, physical examination, investigations and procedures. Interactive interfaces powered by Large Language Models (LLMs) present new opportunities to both assist and automate aspects of this process. In this study, we introduce an LLM optimized for diagnostic reasoning, and evaluate its ability to generate a DDx alone or as an aid to clinicians. 20 clinicians evaluated 302 challenging, real-world medical cases sourced from the New England Journal of Medicine (NEJM) case reports. Each case report was read by two clinicians, who were randomized to one of two assistive conditions: either assistance from search engines and standard medical resources, or LLM assistance in addition to these tools. All clinicians provided a baseline, unassisted DDx prior to using the respective assistive tools. Our LLM for DDx exhibited standalone performance that exceeded that of unassisted clinicians (top-10 accuracy 59.1% vs 33.6%, [p = 0.04]). Comparing the two assisted study arms, the DDx quality score was higher for clinicians assisted by our LLM (top-10 accuracy 51.7%) compared to clinicians without its assistance (36.1%) (McNemar's Test: 45.7, p < 0.01) and clinicians with search (44.4%) (4.75, p = 0.03). Further, clinicians assisted by our LLM arrived at more comprehensive differential lists than those without its assistance. Our study suggests that our LLM for DDx has potential to improve clinicians' diagnostic reasoning and accuracy in challenging cases, meriting further real-world evaluation for its ability to empower physicians and widen patients' access to specialist-level expertise

Age-Related Changes of Peak Width Skeletonized Mean Diffusivity (PSMD) Across the Adult Lifespan: A Multi-Cohort Study

Parameters of water diffusion in white matter derived from diffusion-weighted imaging (DWI), such as fractional anisotropy (FA), mean, axial, and radial diffusivity (MD, AD, and RD), and more recently, peak width of skeletonized mean diffusivity (PSMD), have been proposed as potential markers of normal and pathological brain ageing. However, their relative evolution over the entire adult lifespan in healthy individuals remains partly unknown during early and late adulthood, and particularly for the PSMD index. Here, we gathered and analyzed cross-sectional diffusion tensor imaging (DTI) data from 10 population-based cohort studies in order to establish the time course of white matter water diffusion phenotypes from post-adolescence to late adulthood. DTI data were obtained from a total of 20,005 individuals aged 18.1 to 92.6 years and analyzed with the same pipeline for computing skeletonized DTI metrics from DTI maps. For each individual, MD, AD, RD, and FA mean values were computed over their FA volume skeleton, PSMD being calculated as the 90% peak width of the MD values distribution across the FA skeleton. Mean values of each DTI metric were found to strongly vary across cohorts, most likely due to major differences in DWI acquisition protocols as well as pre-processing and DTI model fitting. However, age effects on each DTI metric were found to be highly consistent across cohorts. RD, MD, and AD variations with age exhibited the same U-shape pattern, first slowly decreasing during post-adolescence until the age of 30, 40, and 50 years, respectively, then progressively increasing until late life. FA showed a reverse profile, initially increasing then continuously decreasing, slowly until the 70s, then sharply declining thereafter. By contrast, PSMD constantly increased, first slowly until the 60s, then more sharply. These results demonstrate that, in the general population, age affects PSMD in a manner different from that of other DTI metrics. The constant increase in PSMD throughout the entire adult life, including during post-adolescence, indicates that PSMD could be an early marker of the ageing process