Gut Microbiota as Therapeutic Targets in Diabetes Management: Opportunities and Challenges

This article delves into the complex interplay between Type 2 Diabetes Mellitus (T2DM), gut microbiota, and dietary strategies for effective diabetes management. T2DM, characterized by insulin resistance and β-cell dysfunction, is influenced by genetic and environmental factors. The gut-brain axis and alterations in incretin functioning contribute to gastrointestinal permeability in T2DM. Plant-based diets offer substantial benefits for managing T2DM by improving emotional well-being, HbA1c levels, weight, and cholesterol. High-fiber diets positively impact gut microbiota, serum metabolism, and emotional health in T2DM individuals. Probiotics, prebiotics, synbiotics, and postbiotics (PPSP) are emerging as pivotal interventions. Probiotics improve serum fructosamine, HbA1c, and cholesterol levels, while prebiotics like oligofructose-enriched inulin and synbiotics enhance glycemic control and lipid profiles. Insights from microbiome studies in diverse dietary populations provide personalized approaches for diabetes management. Integrating plant-based nutrition, PPSP interventions, and microbiome-focused strategies may offer a comprehensive and effective approach to T2DM management, addressing physiological aspects and empowering individuals in their health journey

A survey of the estimated cost of surgical consumable items within trauma and orthopaedic departments

Introduction The impact of the current economic and environmental climate, both nationally and globally, is further straining the NHS. This has led to scrutiny of high-expenditure areas, including consumables. Clinician's knowledge surrounding health economics is sparse, and we conducted this survey to assess cost-awareness within the Trauma and Orthopaedic (T&O) departmental staff. Methods A questionnaire was digitally distributed to T&O staff in the East Kent Hospitals Trust. This included demographic data and to make estimations of the cost of 10 specialty-specific items. The data were analysed to determine the average, median, and interquartile range (IQR) of the estimated prices and compared to the actual costs. Results Approximately 7.1% of all item estimates were deemed 'correct'. No correlation was seen between years of staff experience and the accuracy of estimates. 'Kenalog 1 mL ampoule' (Kenalog, Bristol-Myers Squibb, NJ) had the highest accuracy of estimation across all responses (13%), whilst both 'kirschner wires' and '3.2 drill bit' had the lowest accuracy (4% each). The median estimated cost was closest to the actual cost for 'cement pack' (median estimate/actual cost = 0.9). The median estimated cost was furthest from the actual cost for 'tourniquet cuffs' (median estimate/actual cost = 0.16). 'Velcro wrist splint' was the item that was the most overestimated (median estimate/actual cost = 1.57), with only two of the 10 items being overestimated ('velcro wrist splint' and 'dynamic hip screw and plate'). The most underestimated item was 'tourniquet cuffs' (median estimate/actual cost = 0.16). Conclusions There is a paucity of knowledge surrounding the cost of specialist T&O consumables. The limitations included the sample size (98 respondents) and geographical area (East Kent Hospitals Trust). This study shows that there is a need for further research into this topic, with long-term outcomes, which may be beneficial both economically and environmentally. [Abstract copyright: Copyright © 2024, Divekar et al.

Original research: Trauma exposure and posttraumatic stress disorder among employees of New York City companies affected by the september 11, 2001 attacks on the World Trade Center

OBJECTIVE: Several studies have provided prevalence estimates of posttraumatic stress disorder (PTSD) related to the September 11, 2001 (9/11) attacks in broadly affected populations, although without sufficiently addressing qualifying exposures required for assessing PTSD and estimating its prevalence. A premise that people throughout the New York City area were exposed to the attacks on the World Trade Center (WTC) towers and are thus at risk for developing PTSD has important implications for both prevalence estimates and service provision. This premise has not, however, been tested with respect to DSM-IV-TR criteria for PTSD. This study examined associations between geographic distance from the 9/11 attacks on the WTC and reported 9/11 trauma exposures, and the role of specific trauma exposures in the development of PTSD. METHODS: Approximately 3 years after the attacks, 379 surviving employees (102 with direct exposures, including 65 in the towers, and 277 with varied exposures) recruited from 8 affected organizations were interviewed using the Diagnostic Interview Schedule/Disaster Supplement and reassessed at 6 years. The estimated closest geographic distance from the WTC towers during the attacks and specific disaster exposures were compared with the development of 9/11–related PTSD as defined by the Diagnostic and Statistical Manual, Fourth Edition, Text Revision. RESULTS: The direct exposure zone was largely concentrated within a radius of 0.1 mi and completely contained within 0.75 mi of the towers. PTSD symptom criteria at any time after the disaster were met by 35% of people directly exposed to danger, 20% of those exposed only through witnessed experiences, and 35% of those exposed only through a close associate’s direct exposure. Outside these exposure groups, few possible sources of exposure were evident among the few who were symptomatic, most of whom had preexisting psychiatric illness. CONCLUSIONS: Exposures deserve careful consideration among widely affected populations after large terrorist attacks when conducting clinical assessments, estimating the magnitude of population PTSD burdens, and projecting needs for specific mental health interventions

Rise of the Political Right in India: Hindutva-Development Mix, Modi Myth, and Dualities

We are witnessing a global phenomenon of the rise of right-wing leaders who combine nationalist rhetoric with a claim to challenge the pernicious effects of neoliberalism. But, upon achieving power, they do not oppose the business elite, instead, while paying lip service to the victims of economic processes, they direct the blame for those structural problems upon the minorities and ‘Others’ within the rightwing nationalist imagination. In the Indian context, this is typified by the rise of Narendra Modi. Modi-led BJP (Bharatiya Janata Party) and its coming to power in 2014 has similarities with Trump, and is also different from the earlier incarnations of the BJP. In the first part of this paper, I explain the innovative nature of the specific Modi-mix of Hindutva and Development, and outline the toxic impact his right-wing populist givernment has had on a broad spectrum of Indian society and polity. However, in spite of the visible increase in real and symbolic violence across the country, Modi continues to remain popular and wield great influence. The second part of the paper answers this apparent puzzle by providing an account of the work of the ‘Modi myth’ that projects him as an ascetic, paternal and decisive ruler. This political myth is constantly reinforced through medium, speech, and performance. Further, given the many disparate constituencies with differing concerns that Modi-led BJP addresses itself to, the policy inconsistencies are reconciled by a strategic and systematic use of ‘forked tongue’ speech that presents the different interests as being uniform. A populist right-wing politics is constructed out of keeping these dualities in motion by speaking to the different constituencies with a forked tongue. I conclude by giving three examples of management of such dual domains: corporate/grassroots, national/international, India/Bharat

Difference in clinical profile between juvenile onset and adult-onset systemic lupus erythematosus: a meta-analysis

The aim was to systematically review the studies that compared clinical and serological variation between adult-onset systematic lupus erythematosus (aSLE) andjuvenile-onset systematic lupus erythematosus (jSLE). A comprehensive literature search was done, in various available electronic databases for relevant publication that compared juvenile onset SLE and adult onset SLE. The data of adverse clinical features, serological profile and mortality were extracted. Juvenile onset was defined as 18 years. The methodological quality of study was assessed by Newcastle Ottawa scale (NOS) criteria and R version 3.3.1 was used for analysis and ORs and 95% CIs, were used as statistical parameter. A total of 14,920 patients; (12,230: aSLE, and 2,690: jSLE) were included. Renal involvement especially nephritis was significantly more in j-SLE OR: 2.18, 95% CI: [1.81;2.62]; I2=10.8% whereas musculoskeletal was significant in aSLE O.R: 0.64; C.I: [0.44; 0.93]; I2=83.4%. Seizure and malar rash were significantly higher in J-SLE OR:1.69, CI: [1.31; 2.18]; I2=31.1%,1.43; C.I [1.04; 1.97]; I2=82%, respectively. Raynaud’s phenomenon and pleuritis were significantly higher in adult onset SLE. Anemia and thrombocytopenia were significantly higher in juvenile onset SLE. Anti-ds DNA, anti-histone, and anti-ribosomal-P were more frequent in juvenile-onset SLE while, anti-Ro was more common in adult-onset disease. The cause of mortality was not significantly different in both groups. Renal biopsy of class III and IV combined and class V were significantly more in adult-onset SLE. SLEDAI was higher in j-SLE. Meta-analysis indicated that, regardless of many similar clinical and serological manifestations, there is still some variation between adult-onset SLE and juvenile-onset SLE. Although, SLE disease is continuum from juvenile to adult but disease aggressive in juvenile onset SLE

Effective and durable repigmentation for stable vitiligo: A randomized within-subject controlled trial assessing treatment with autologous skin cell suspension transplantation

BackgroundVitiligo lesions are often challenging to repigment with conventional medical therapies. Surgical autologous melanocyte transfer methods can be utilized for stable vitiligo but demand specialized skills and equipment. A point-of-care autologous cell harvesting device was designed enabling simple preparation of autologous skin cell suspension (ASCS) containing melanocytes, keratinocytes, and fibroblasts providing a straightforward approach for cellular transplantation.ObjectiveTo evaluate the safety and effectiveness of ASCS for repigmentation of stable vitiligo lesions among adults.MethodsA US multicenter, randomized, within-subject controlled trial compared ASCS to narrow band ultraviolet B only (Control) in similar vitiligo lesions. ASCS was applied after laser skin resurfacing and followed by narrow band ultraviolet B treatment. The primary effectiveness endpoint was the proportion of lesions achieving ≥80% repigmentation at week-24. Repigmentation durability was assessed at week-52.ResultsAmong 25 subjects, 36% of ASCS-treated lesions achieved ≥80% repigmentation at week-24 compared to 0% for Control (P < .025), with durability through week-52. The safety profile of ASCS was acceptable, with favorable patient- and investigator-reported outcomes.LimitationsStudy sample size limited robust subgroup analyses.ConclusionApplication of ASCS has potential as a treatment for repigmentation of stable vitiligo lesions with the potential to improve health-related quality of life and reduce burden of disease

Autologous Cell Harvesting Device Provides Repigmentation and Improves Quality-of-Life for Patients with Stable Vitiligo Lesions in a Large and Diverse Patient Population: A pre-post study

IntroductionThe mental health burden associated with vitiligo can significantly impact patients' quality-of-life. Although successful for repigmentation of stable vitiligo, adoption of surgical melanocyte transplantation remains limited due to time and skilled-expertise requirements. A cell harvesting device prepares autologous skin cell suspension (ASCS) at point of care, simplifying the process.ObjectiveTo confirm early and favorable repigmentation response and evaluate health-related quality-of-life changes following ASCS treatment of stable vitiligo.MethodsIn this large (N = 107), prospective, multicenter study, vitiligo lesions were laser-ablated and received ASCS treatment followed by at-home phototherapy.ResultsAll Fitzpatrick skin types and major vitiligo subtypes were represented. Excellent repigmentation response (≥80%) was observed by week 4. By week-24, all lesions demonstrated improvement; 67% achieved >50% repigmentation, 42% achieved ≥80% repigmentation, and 8% achieved complete repigmentation. Vitiligo Noticeability Scale response was attained by 27.7% of lesions; 72.3% of patients reported treatment satisfaction. Significant improvement from baseline in Vitiligo Quality-of-Life Instrument (P < .05) was observed at week-24.LimitationsNo control.ConclusionsThe cell harvesting device provides a simplified, more accessible technique for melanocyte transplantation. ASCS is highly effective for repigmentation of stable vitiligo lesions, with positive patient-reported outcomes and improvement in quality-of-life, as demonstrated in this large, diverse population

High Resolution Methylome Map of Rat Indicates Role of Intragenic DNA Methylation in Identification of Coding Region

DNA methylation is crucial for gene regulation and maintenance of genomic stability. Rat has been a key model system in understanding mammalian systemic physiology, however detailed rat methylome remains uncharacterized till date. Here, we present the first high resolution methylome of rat liver generated using Methylated DNA immunoprecipitation and high throughput sequencing (MeDIP-Seq) approach. We observed that within the DNA/RNA repeat elements, simple repeats harbor the highest degree of methylation. Promoter hypomethylation and exon hypermethylation were common features in both RefSeq genes and expressed genes (as evaluated by proteomic approach). We also found that although CpG islands were generally hypomethylated, about 6% of them were methylated and a large proportion (37%) of methylated islands fell within the exons. Notably, we obeserved significant differences in methylation of terminal exons (UTRs); methylation being more pronounced in coding/partially coding exons compared to the non-coding exons. Further, events like alternate exon splicing (cassette exon) and intron retentions were marked by DNA methylation and these regions are retained in the final transcript. Thus, we suggest that DNA methylation could play a crucial role in marking coding regions thereby regulating alternative splicing. Apart from generating the first high resolution methylome map of rat liver tissue, the present study provides several critical insights into methylome organization and extends our understanding of interplay between epigenome, gene expression and genome stability

The Emergence of Emotions

Emotion is conscious experience. It is the affective aspect of consciousness. Emotion arises from sensory stimulation and is typically accompanied by physiological and behavioral changes in the body. Hence an emotion is a complex reaction pattern consisting of three components: a physiological component, a behavioral component, and an experiential (conscious) component. The reactions making up an emotion determine what the emotion will be recognized as. Three processes are involved in generating an emotion: (1) identification of the emotional significance of a sensory stimulus, (2) production of an affective state (emotion), and (3) regulation of the affective state. Two opposing systems in the brain (the reward and punishment systems) establish an affective value or valence (stimulus-reinforcement association) for sensory stimulation. This is process (1), the first step in the generation of an emotion. Development of stimulus-reinforcement associations (affective valence) serves as the basis for emotion expression (process 2), conditioned emotion learning acquisition and expression, memory consolidation, reinforcement-expectations, decision-making, coping responses, and social behavior. The amygdala is critical for the representation of stimulus-reinforcement associations (both reward and punishment-based) for these functions. Three distinct and separate architectural and functional areas of the prefrontal cortex (dorsolateral prefrontal cortex, orbitofrontal cortex, anterior cingulate cortex) are involved in the regulation of emotion (process 3). The regulation of emotion by the prefrontal cortex consists of a positive feedback interaction between the prefrontal cortex and the inferior parietal cortex resulting in the nonlinear emergence of emotion. This positive feedback and nonlinear emergence represents a type of working memory (focal attention) by which perception is reorganized and rerepresented, becoming explicit, functional, and conscious. The explicit emotion states arising may be involved in the production of voluntary new or novel intentional (adaptive) behavior, especially social behavior