New Advances In Treatment Research Articles

Single Nucleus Total RNA Sequencing of Formalin-Fixed Paraffin-Embedded Gliomas.

Gliomas, the predominant form of brain cancer, comprise diverse malignant subtypes with limited curative therapies available. The insufficient understanding of their molecular diversity and evolutionary processes hinders the advancement of new treatments. Technical complexities associated with formalin-fixed paraffin-embedded (FFPE) clinical samples hinder molecular-level analyses of gliomas. Current single-cell RNA sequencing (scRNA-seq) platforms are inadequate for large-scale clinical applications. In this study, automated snRandom-seq is developed, a high-throughput single-nucleus total RNA sequencing platform optimized for archival FFPE samples. This platform integrates automated single-nucleus isolation and droplet barcoding systems with the random primer-based scRNA-seq chemistry, accommodating a broad spectrum of sample types. The automated snRandom-seq is applied to analyze 116492 single nuclei from 17 FFPE samples of various glioma subtypes, including rare clinical samples and matched primary-recurrent glioblastomas (GBMs). The study provides comprehensive insights into the molecular characteristics of gliomas at the single-cell level. Abundant non-coding RNAs (ncRNAs) with distinct expression profiles across different glioma clusters and uncovered promising recurrence-related targets and pathways in primary-recurrent GBMs are identified. These findings establish automated snRandom-seq as a robust tool for scRNA-seq of FFPE samples, enabling exploration of molecular diversities and tumor evolution. This platform holds significant implications for large-scale integrative and retrospective clinical research.

New advances in the treatment and diagnosis of hypertension in primary care: a literature review

Background: Despite the availability of safe and effective antihypertensive drugs, hypertension continues to be a major risk factor for cardiovascular death and morbidity worldwide. This review explores the contemporary landscape of advances in hypertension (HTN) diagnosis and treatment, examining the discordant diagnostic thresholds proposed by American and European guidelines. Methods: An integrative approach was employed, analyzing pertinent literature from sources such as ScienceDirect, Google Scholar, and PubMed. Inclusion criteria encompassed studies on new advances in HTN diagnosis and treatment in primary care, published in English within the last five years (2018-2023). Results: Diagnostic innovations focus on the preference for automated sphygmomanometers and technological advancements, enhancing precision and reliability. Treatment advancements span neurovascular dimensions, including neuromodulation, and innovations in the renin-angiotensin-aldosterone system, showcasing promising drugs like finerenone and esaxerenone. Sodium-glucose cotransporter-2 inhibitors demonstrate efficacy beyond antidiabetic effects. The complexities of renal denervation and its challenges are scrutinized, emphasizing the need for further research. Clinical decision-making underscores risk stratification, lifestyle modifications, and the emerging use of single-pill combinations and individualized treatment plans. Conclusion: The review highlights the multidimensional approach required for optimal HTN management in primary care, encompassing diagnostic innovations, treatment advancements, and individualized strategies. Ongoing research is pivotal for refining diagnostic and therapeutic paradigms in hypertension management.

The antagonistic effects of temozolomide and trichostatin a combination on MGMT and DNA mismatch repair pathways in Glioblastoma.

Glioblastoma is the most aggressive and fatal form of brain cancer. Despite new advancements in treatment, the desired outcomes have not been achieved. Temozolomide (TMZ) is the first-choice treatment for the last two decades and has improved survival rates. Emerging studies have shown that targeting epigenetics in glioblastoma can be beneficial when combined with clinically used treatments. Trichostatin A (TSA), a histone deacetylase inhibitor, has anti-cancer properties in various cancers. No data concerning the TMZ and TSA relationship was shown previously in glioblastoma therefore, we aimed to determine the likely therapeutic effect of the TMZ and TSA combination in glioblastoma. The T98G and U-373 MG, glioblastoma cell lines, were used in this study. TMZ and TSA cytotoxicity and combination index were performed by MTT assay. The expression of DNA repair genes (MGMT, MLH-1, PMS2, MSH2 and MSH6) was detected using RT-PCR. One-way analysis of variance (ANOVA) was used for statistical analysis. Combination index calculations revealed antagonistic effects of TMZ and TSA in terms of cytotoxicity. Antagonistic effects were more apparent in the T98G cell line, which is expressing MGMT relatively higher. MGMT and DNA Mismatch Repair (MMR) genes were upregulated in the T98G cell line, whereas downregulated in the U373-MG cell lines under TMZ and TSA combination treatment. It is concluded that MGMT might be playing a more active part than MMR genes in TMZ resistance to TMZ and TSA antagonism. This is the first study elucidating the TMZ and TSA relationship in cancer cell lines.

Mesenchymal Stem Cell-Derived Extracellular Vesicles: Hype or Hope for Skeletal Muscle Anti-Frailty.

Steadily rising population ageing is a global demographic trend due to the advancement of new treatments and technologies in the medical field. This trend also indicates an increasing prevalence of age-associated diseases, such as loss of muscle mass (sarcopenia), which tends to afflict the older population. The deterioration in muscle function can cause severe disability and seriously affects a patient's quality of life. Currently, there is no treatment to prevent and reverse age-related skeletal muscle ageing frailty. Existing interventions mainly slow down and control the signs and symptoms. Mesenchymal stem cell-derived extracellular vesicle (MSC-EV) therapy is a promising approach to attenuate age-related skeletal muscle ageing frailty. However, more studies, especially large-scale randomised clinical trials need to be done in order to determine the adequacy of MSC-EV therapy in treating age-related skeletal muscle ageing frailty. This review compiles the present knowledge of the causes and changes regarding skeletal muscle ageing frailty and the potential of MSC-EV transplantation as a regenerative therapy for age-related skeletal muscle ageing frailty and its clinical trials.

Immune cells and immune cell-targeted therapy in chronic pancreatitis.

In recent years, studies have attempted to understand the immune cells and mechanisms underlying the pathogenesis of chronic pancreatitis (CP) by constructing a model of CP. Based on these studies, the innate immune response is a key factor in disease pathogenesis and inflammation severity. Novel mechanisms of crosstalk between immune and non-immune pancreatic cells, such as pancreatic stellate cells (PSC), have also been explored. Immune cells, immune responses, and signaling pathways in CP are important factors in the development and progression of pancreatitis. Based on these mechanisms, targeted therapy may provide a feasible scheme to stop or reverse the progression of the disease in the future and provide a new direction for the treatment of CP. This review summarizes the recent advances in research on immune mechanisms in CP and the new advances in treatment based on these mechanisms.

CN45 The Gastrointestinal and Lymphoma Unit Advanced Nurse Practitioner role in clinical research at The Royal Marsden Hospital

The Advanced Nurse Practitioner (ANP) role is a new concept in all fields of nursing practice, dating back to 1990. The role of the ANP is invaluable, allowing patients to receive timely care and negates delays in treatment. In the UK, the role continues to develop in response to the changing healthcare needs of our population including an ageing society, increasing prevalence of chronic conditions, the advancement of new treatments, inefficient healthcare policies and the rising cost of healthcare.

Pharmaceutical potential of active compounds from plants

Alzheimer's illness (AD) is an issue that causes cell degeneration in the cerebrum and is the primary driver of dementia, which is described by a lessening in thought and freedom in private everyday exercises. Promotion is viewed as a multifactorial sickness: two primary speculations were proposed as a reason for theories of commercials, cholinergic and amyloids. Moreover, a few gamble factors, like expanding age, hereditary variables, head wounds, vascular illnesses, contaminations, and natural elements, assume a part in the infection. At present, there are just two sorts of meds endorsed to treat AD, including cholinesterase compound inhibitors and N-methyl D-aspartate (NMDA) bad guys, who are powerful just in the treatment of AD side effects, yet don't fix or keep you from disease. Today, research is zeroing in on the comprehension of AD pathology focused on a few systems, like strange tau protein digestion, β-amyloid, fiery reaction, and cholinergic and free extreme harm, with the target of creating effective medicines to stop or alter the course of the declaration. This survey presently examines accessible drugs and future hypotheses for the advancement of new treatments for AD and normal mixtures.

Financial toxicity in patients with lung cancer: a scoping review protocol

IntroductionLung cancer has the second-ranked morbidity rate and the first-ranked mortality rate worldwide. With the progression of the cancer condition and the advancement of new treatments, the corresponding medical expenses...

New advances in treatment of dry eye disease

New advances in treatment of dry eye disease - IJCEO- Print ISSN No: - 2395-1443 Online ISSN No:- 2395-1451 Article DOI No:- 10.18231/j.ijceo.2021.120, Indian Journal of Clinical and Experimental Ophthalmology-Indian J Clin Exp Ophthalmol

Adult Acquired Flatfoot Deformity.

Adult acquired flatfoot deformity (AAFD) is a condition commonly seen by orthopaedic surgeons. Posterior tibial tendon dysfunction is thought to be the initial pathoanatomic etiology that leads to this deformity. Successful resolution of the pain associated with AAFD can be achievable with nonsurgical methods. Patients who continue to have pain or functional limitations despite nonsurgical treatment can find improvement with appropriately selected surgical interventions. This article addresses new advances in treatment based on the stage of AAFD and will identify areas of continued development with a focus on surgical management. The literature continues to evolve as demonstrated by a recent update regarding the nomenclature and treatment of this condition to progressive collapsing flatfoot deformity. Future goals of research include understanding the natural history of the disease, from asymptomatic to symptomatic, and studying a wide array of newer treatments and implants that have not been prospectively evaluated.

Mesenchymal Stem Cell Transplantation for the Treatment of Age-Related Musculoskeletal Frailty.

Projected life expectancy continues to grow worldwide owing to the advancement of new treatments and technologies leading to rapid growth of geriatric population. Thus, age-associated diseases especially in the musculoskeletal system are becoming more common. Loss of bone (osteoporosis) and muscle (sarcopenia) mass are conditions whose prevalence is increasing because of the change in population distribution in the world towards an older mean age. The deterioration in the bone and muscle functions can cause severe disability and seriously affects the patients’ quality of life. Currently, there is no treatment to prevent and reverse age-related musculoskeletal frailty. Existing interventions are mainly to slow down and control the signs and symptoms. Mesenchymal stem cell (MSC) transplantation is a promising approach to attenuate age-related musculoskeletal frailty. This review compiles the present knowledge of the causes and changes of the musculoskeletal frailty and the potential of MSC transplantation as a regenerative therapy for age-related musculoskeletal frailty.

Roadmap for Advancing Pre-Clinical Science in Traumatic Brain Injury.

Pre-clinical models of disease have long played important roles in the advancement of new treatments. However, in traumatic brain injury (TBI), despite the availability of numerous model systems, translation from bench to bedside remains elusive. Integrating clinical relevance into pre-clinical model development is a critical step toward advancing therapies for TBI patients across the spectrum of injury severity. Pre-clinical models include in vivo and ex vivo animal work—both small and large—and in vitro modeling. The wide range of pre-clinical models reflect substantial attempts to replicate multiple aspects of TBI sequelae in humans. Although these models reveal multiple putative mechanisms underlying TBI pathophysiology, failures to translate these findings into successful clinical trials call into question the clinical relevance and applicability of the models. Here, we address the promises and pitfalls of pre-clinical models with the goal of evolving frameworks that will advance translational TBI research across models, injury types, and the heterogenous etiology of pathology.

HAIR LOSS: CAUSES AND PATHOLOGY

There are many diseases in which one of the main symptoms is hair loss. Hair loss in medical terms is called "Alopecia". Many reasons can cause alopecia. Hair loss can be due to nutritional factors, genetic problems, metals toxicity, and body inflammation. Hormonal changes in the body can also lead to a loss of hair. Physiology and stages of reproduction of hair in humans are also discussed. There are three stages in the process of the hair reproduction cycle. Many factors can be responsible for the disruption of hair, and stress is one of them. A hair pulling test should be done to check the quality of hair. Doctors prescribe the medication and treatment according to the cause of the hair loss. If the hair loss is due to nutritional changes, proper diet and supplements should be taken to reduce the hair loss. A clinical evaluation of a patient with hair loss is important to conclude. Doctors should keep themselves refreshed with the new advances in treatment. Age factor is one of the primary reasons for hair color changes and hair loss. Trichotillomania and traction alopecia are the two types of self-inflicted hair loss that involve pulling the hair and heat, worsening hair condition using hair straighteners, respectively.

Identifying New Drug Targets by Illuminating the Druggable Genome

Results from the Human Genome Project have revealed that the human genome contains ~20,000 genes. Of these, ~4,500 genes are considered part of the “druggable genome,” defined as the subset of the human genome that expresses proteins that are able to bind drug-like molecules. However, existing clinical drugs only target a few hundred of these proteins, leaving a subset of ~4000 proteins within this druggable genome that still remain largely understudied. Three protein families, the ion channels, G-protein-coupled receptors, and protein kinases, have been identified to contain adequate numbers of understudied members and are well-established druggable families with high potential to impact human health once disease associations are made. Further investigation is warranted to discover crucial knowledge about the function of understudied members of these protein families and to elucidate their roles in health and disease. To improve our scientific understanding of understudied members of these three protein families, the National Institutes of Health (NIH) Common Fund launched the Illuminating the Druggable Genome (IDG) Program in 2014. The overall goal of the IDG Program is to catalyze research in areas of biology that are currently understudied but that have high potential to impact human health by (1) identifying biochemical, cellular, or animal model phenotypes for understudied proteins from druggable gene families, (2) enabling further investigation of those proteins by providing reagents and tools, and (3) generating, maintaining, and facilitating the use of a minable knowledge base. A key resource from this program, Pharos (https://pharos.nih.gov/idg/index), aggregates protein information from several sources, allowing researchers easy access to in depth protein data, enabling them to enhance their research and help identify new targets of interest. In addition, the IDG program works to develop molecular probes (small molecules), molecular tools and assays, transgenic mice, recombinant cell lines, data, and digital resources for 100+ orphan GPCRs, ion channels and kinases. These resources are now available for use by the scientific community, with the IDG Program continuing to build on the knowledge and tools developed and generate, aggregate, analyze, and disseminate knowledge and tools around understudied proteins. These new knowledge and tool sets are intended to equip the scientific community, including small businesses and the pharmaceutical industry, with the ability to explore previously understudied biology with the potential to rapidly impact human health. It is hoped that the resources developed, and the discoveries made by the IDG Program, will enable the advancement of new treatments and diagnostics in order to get more treatments to more patients more quickly.

Lupus Nephritis; Pathogenesis and Treatment Update Review

Lupus nephritis (LN) is a serious complication of systemic lupus erythematosus (SLE). LN is a leading cause of morbidity and mortality in SLE patients. LN presents with various symptoms and signs, ranging from asymptomatic renal involvement to End-Stage Renal Failure (ESRD). The pathogenesis of LN is not clearly understood, however, there are extra and intra-renal underlying factors that have been postulated in LN pathogenesis. Renal biopsy is crucial to stage LN and to rule out other causes. Histopathological studies have shown six different types of LN. Knowing the histopathological lesion, chronicity and the disease activity are essential to plan the LN treatment and to predict the outcome. There are different regimens for treating LN. In this review, LN pathogenesis and new advances in treatment will be briefly reviewed.

Thyroid and Its New Advances in Treatment

Thyroid and Its New Advances in Treatment

Retrospective observational cohort study on innovation in oncology and progress in survival: How far have we gotten in the two decades of treating patients with advanced non-small cell lung cancer as a single population?

We assessed the impact of new antineoplastic agents on the overall survival (OS) of advanced non-small cell lung cancer (aNSCLC) patients followed up until 2012. Multivariate regression models were run for OS (outcome) and four proxies for innovation (exposure): Index (InnovInd, for SEER-Research data 1973–2012) and three levels of aggregation of Mean Medication Vintage, i.e. Overall (MMVOverall), using data aggregated at the State Level (MMVState), and using patient-level data (MMVPatient) using data from the US captured in SEER-Medicare 1991–2012. We derived Hazard ratios (HR) from Royston-Parmar models and odds ratios (OR) from a logistic regression on 1-year OS. Including 164,704 patients (median age 72 years, 56.8% stage IV, 61.8% with no comorbidities, 37.8% with adenocarcinoma, 22.9% with squamous-cell, 6.1% were censored). One-year OS improved from 0.22 in 1973 to 0.39 in 2012, in correlation with InnovInd (r = 0.97). Ten new NSCLC drugs were approved and 28 more used off-label. Regression-models results indicate that therapeutic innovation only marginally reduced the risk of dying (HROverall = 0.98 [0.98–0.98], HRMMV-Patient = 0.98 [0.97–0.98], and HRMMV-State = 0.98 [0.98–0.98], and slightly improved 1-year survival (ORMMV-Overall = 1.05 95%CI [1.04–1.05]). These results were validated with data from the Swedish National Health Data registers. Until 2013, aNSCLC patients were treated undifferentiated and the introduction of innovative therapies had statistically significant, albeit modest, effects on survival. Most treatments used off-guidelines highlight the high unmet need; however new advancements in treatment may further improve survival.

Current and promising novel drug candidates against visceral leishmaniasis

Abstract Leishmaniasis is a group of zoonotic diseases caused by a trypanosomatid parasite mostly in impoverished populations of low-income countries. In their different forms, leishmaniasis is prevalent in more than 98 countries all over the world and approximately 360-million people are at risk. Since no vaccine is currently available to prevent any form of the disease, the control strategy of leishmaniasis mainly relies on early case detection followed by adequate pharmacological treatment that may improve the prognosis and can reduce transmission. A handful of compounds and formulations are available for the treatment of leishmaniasis in humans, but only few of them are currently in use since most of these agents are associated with toxicity problems such as nephrotoxicity and cardiotoxicity in addition to resistance problems. In recent decades, very few novel drugs, new formulations of standard drugs or combinations of them have been approved against leishmaniasis. This review highlights the current drugs and combinations that are used medical practice and recent advances in new treatments against leishmaniasis that were pointed out in the recent 2nd Conference, Global Challenges in Neglected Tropical Diseases, held in San Juan, Puerto Rico in June 2018, emphasizing the plethora of new families of molecules that are bridging the gap between preclinical and first-in-man trials in next future.

A new model for standardising and treating thermal injury in the rat

Thermal burn injury methodologies are inconsistently described within the current literature. To permit the advancement of new treatments there is an urgent need for the development and standardisation of an acute rat model. We describe a rat thermal burn model that involves: anaesthesia, chronic catheterisation, skin preparation, baseline hemodynamic and physiological monitoring, and a quantifiable method to reproduce a severe full-thickness burns injury affecting ∼30% percent of the total body surface area (%TBSA). Following a 15 min post-burn period, treatment commences with an acute monitoring phase lasting up to 8 h, which can be modified according to individual protocols. This model reflects the clinical continuum-of-care from point-of-injury, a 15 min ambulance response time, a 60 min prehospital phase and hospital treatment monitoring phase. The model is validated with histological evidence of full-thickness injury, evidence of the hypermetabolic response (K+, Base Excess, lactate) and changes in complete blood counts.•It has been 50 years since Walker and Mason published their widely popular “A Standard Animal Burn Model”.•The model, however, lacks quantifiable methodology for the assessment of burn thickness, surface area burnt and physiological status.•We present a new standardised method for evaluation of drug and interventional therapies that mimic the clinical scenario including ambulance response, pre-hospital and hospital phases after burn.

New advances in treatment of elderly acute myeloid leukemia

Acute myeloid leukemia (AML) is a group of hematologic malignancy with high heterogeneity. Old people are at a high risk of AML with poor outcome, while compared with younger ones, chemotherapy of elderly patients were always limited by some conditions associated with aging, such as organ dysfunction, debility and more comorbidities. This article reviews the new advances in treatment of elderly AML in recent years, to provide reference on characteristics of elderly AML, evaluations of prognosis in elderly patients with AML, as well as treatment decision making. Key words: Leukemia, myeloid, acute; Elderly; Drug therapy, combination; Prognosis; Drugs, investigational