Revolutionary breakthrough: FDA approves CASGEVY, the first CRISPR/Cas9 gene therapy for sickle cell disease.

Sickle cell disease (SCD) is a hereditary hemoglobinopathy resulting from a ß-globin chain mutation that causes abnormal hemoglobin (HbS) polymerization and leads to severe complications. Current treatment options primarily focus on symptom management, with limited curative potential. Recently, Casgevy, the first CRISPR/Cas9-based gene therapy for SCD, has received breakthrough FDA approval. Clinical trials have shown that Casgevy administered to patients aged older than or equal to 12 years enables precise modifications in hematopoietic stem cells, resulting in elevated fetal hemoglobin (HbF) levels and a significant reduction in vaso-occlusive events. Unlike conventional treatments, this therapy offers a curative approach and eliminates the need for recurrent transfusions and transplants, thereby improving the quality of life of patients with SCD. Casgevy has emerged as a beacon of hope for SCD patients and signifies a potential paradigm shift in SCD management due to its safety, curative potential, and transformative impact, positioning it as a groundbreaking intervention. Nevertheless, ethical considerations surrounding CRISPR technology and regulatory frameworks must be addressed to ensure responsible application and equitable access to this one-time gene editing therapy. As the authors celebrate this scientific advancement, sustained interdisciplinary collaboration and ethical scrutiny are essential to navigating the evolving landscape of CRISPR technology in medicine. This review aims to provide a detailed insight into the application of Casgevy, challenges associated with its application, future prospects of this therapy, and its comparison with existing treatment options for SCD.

State-of-the-Art and New Treatment Approaches for Spinal Cord Tumors.

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

A Narrative Review of the Dorsal Root Ganglia and Spinal Cord Mechanisms of Action of Neuromodulation Therapies in Neuropathic Pain.

Neuropathic pain arises from injuries to the nervous system in diseases such as diabetes, infections, toxicity, and traumas. The underlying mechanism of neuropathic pain involves peripheral and central pathological modifications. Peripheral mechanisms entail nerve damage, leading to neuronal hypersensitivity and ectopic action potentials. Central sensitization involves a neuropathological process with increased responsiveness of the nociceptive neurons in the central nervous system (CNS) to their normal or subthreshold input due to persistent stimuli, leading to sustained electrical discharge, synaptic plasticity, and aberrant processing in the CNS. Current treatments, both pharmacological and non-pharmacological, aim to alleviate symptoms but often face challenges due to the complexity of neuropathic pain. Neuromodulation is emerging as an important therapeutic approach for the treatment of neuropathic pain in patients unresponsive to common therapies, by promoting the normalization of neuronal and/or glial activity and by targeting cerebral cortical regions, spinal cord, dorsal root ganglia, and nerve endings. Having a better understanding of the efficacy, adverse events and applicability of neuromodulation through pre-clinical studies is of great importance. Unveiling the mechanisms and characteristics of neuromodulation to manage neuropathic pain is essential to understand how to use it. In the present article, we review the current understanding supporting dorsal root ganglia and spinal cord neuromodulation as a therapeutic approach for neuropathic pain.

Colorectal Cancer: Disease Process, Current Treatment Options, and Future Perspectives.

Colorectal cancer (CRC) is one of the deadliest malignancies in the US, ranking fourth after lung, prostate, and breast cancers, respectively, in general populations. It continues to be a menace, and the incidence has been projected to more than double by 2035, especially in underdeveloped countries. This review seeks to provide some insights into the disease progression, currently available treatment options and their challenges, and future perspectives. Searches were conducted in the PubMed search engine in the university's online library. The keywords were "Colorectal Cancer" AND "disease process" OR "disease mechanisms" OR "Current Treatment" OR "Prospects". Selection criteria were original articles published primarily during the period of 2013 through 2023. Abstracts, books and documents, and reviews/systematic reviews were filtered out. Of over 490 thousand articles returned, only about 800 met preliminary selection criteria, 200 were reviewed in detail, but 191 met final selection criteria. Fifty-one other articles were used due to cross-referencing. Although recently considered a disease of lifestyle, CRC incidence appears to be rising in countries with low, low-medium, and medium social demographic indices. CRC can affect all parts of the colon and rectum but is more fatal with poor disease outcomes when it is right-sided. The disease progression usually takes between 7-10 years and can be asymptomatic, making early detection and diagnosis difficult. The CRC tumor microenvironment is made up of different types of cells interacting with each other to promote the growth and proliferation of the tumor cells. Significant advancement has been made in the treatment of colorectal cancer. Notable approaches include surgery, chemotherapy, radiation therapy, and cryotherapy. Chemotherapy, including 5-fluorouracil, irinotecan, oxaliplatin, and leucovorin, plays a significant role in the management of CRC that has been diagnosed at advanced stages. Two classes of monoclonal antibody therapies have been approved by the FDA for the treatment of colorectal cancer: the vascular endothelial growth factor (VEGF) inhibitor, e.g., bevacizumab (Avastin®), and the epidermal growth factor receptor (EGFR) inhibitor, e.g., cetuximab (Erbitux®) and panitumumab (Verbitix®). However, many significant problems are still being experienced with these treatments, mainly off-target effects, toxic side effects, and the associated therapeutic failures of small molecular drugs and the rapid loss of efficacy of mAb therapies. Other novel delivery strategies continue to be investigated, including ligand-based targeting of CRC cells.

Direct Current Treatment Tuning Crystallinity Leading to High-Performance p-Type Sb2Te3 Flexible Thin Films.

With the development of wearable electronics, inorganic flexible thin films (f-TFs) with high thermoelectric performance have attracted increasing research interest. To further enhance the thermoelectric performance of p-type inorganic Sb2Te3-based f-TFs, we employed direct current treatment to tune the crystallinity by rationally tuning the direct current treatment time. Correspondingly, a high electrical conductivity of >845 S cm-1 and a moderate Seebeck coefficient of >110 µV K-1 within the entire measurement temperature range have been simultaneously achieved. Consequently, a high power factor of 12.84 µW cm-1 K-2 at 423 K has been realized in the as-prepared p-type Sb2Te3 f-TF treated by a direct current of 5 A for 4 min. A flexible thermoelectric device has been further assembled to demonstrate the power-generating capacity. This study indicates that the direct current treatment is an effective method to improve the thermoelectric performance of Sb2Te3 f-TFs.

A Journey Through JAK Inhibitors for the Treatment of Myeloproliferative Diseases.

PURPOSE OF REVIEW: Chronic myeloproliferative neoplasms (MPN) represent a group of diseases characterised by constitutive activation of the JAK/STAT pathway in a clonal myeloid precursor. The therapeutic approach aims to treat the symptom burden (headache, itching, debilitation), splenomegaly, slow down the fibrotic proliferation in the bone marrow and reduce the risk of thrombosis/bleeding whilst avoiding leukaemic transformation. RECENT FINDINGS: In recent years, the advent of JAK inhibitors (JAKi) has significantly broadened treatment options for these patients. In myelofibrosis, symptom control and splenomegaly reduction can improve quality of life with improved overall survival, not impacting progression into acute leukaemia. Several JAKi are available and used worldwide, and combination approaches are now being explored. In this chapter, we review the approved JAKi, highlighting its strengths, exploring potential guidelines in choosing which one to use and reasoning towards future perspectives, where the combinations of therapies seem to promise the best results.

Current Treatment Status and Treatment Seeking Time of Breast Cancer Patients during COVID-19 Pandemic in Bangladesh.

BACKGROUND: Rising incidence of cancer is a challenging form of seeking help to start treatment, especially in a pandemic situation. Treatment in due time may reduce the time interval of treatment-seeking, which influences the survival of breast cancer patients. The objective of this study was to determine the effect of the pandemic on treatment delays among breast cancer patients in Bangladesh. METHOD: A cross-sectional study was conducted from July 2020 to June 2021. A total of 200 samples were collected randomly from the out clinic department of the National Institute of Cancer Research and Hospital. A face-to-face interview was taken with a pretested semi-structured questionnaire. Patients were selected by histopathologically confirmed breast cancer and excluded by their metastasis history, treatment history, physical condition, and informed consent. RESULTS: Mean illness period was 16 months with patient delay was 4 months, provider delay was 7 months and total (treatment delay) was 11 months. Stage of cancer had 6 times chance to develop patient delay where OR of 6.234 at 95% CI (2.0, 19.23) and p-value 0.001, Stage of cancer had 4 times chance to develop provider delay where OR of 4.513 at 95% CI (1.35, 12.15) and p-value 0.012, to whom first seek help had 5 times chance to develop provider delay OR of 5.287 at 95% CI (2.58, 10.84) and p-value <0.0001. Provider delay was 2 times associated with a number of FNAC at 95% CI (1.13, 5.13) and a p-value of 0.023. Stage of cancer had 8 times chance to develop total delay where OR of 7.960, at 95% CI (3.20, 19.75) and p-value <0.0001, to whom first seek help had 4 times chance to develop total delay OR 3.860 at 95% CI (1.88, 7.95) and p-value <0.0001. CONCLUSION: Stage of cancer and first health care provider play a role in treatment-seeking, so, to improve treatment-seeking time, health education is needed to whom they go first, to where they go first.

Silicosis: New Challenges from an Old Inflammatory and Fibrotic Disease.

Silicosis, an occupational lung disease that can be prevented, is still a significant public health concern in many countries, despite its considerably decreased incidence over the years. The latency period for silicosis ranges from a few years to several decades, depending on the duration and intensity of exposure to silica dust. The complex pathogenic mechanisms of the disease are not fully understood, but it is known to be characterized by inflammation, the formation of silicotic nodules, and progressive and irreversible fibrosis. The aim of this paper was to present the current sources of exposure to silica dust and summarize the updates on risk factors (e.g., socioeconomic status, genetic susceptibility) and sex differences, silico-tuberculosis, prognostic markers including 16-kDa Clara cell secretory protein, antifibrotic treatment, and other therapeutic possibilities with promising results. There are no effective treatment options for silicosis, and prevention remains the primary tool to significantly reduce the risk of disease. There are promising new treatments under investigation including antifibrotic, cellular, and immunomodulatory therapies, but further research is needed to demonstrate the efficacy and safety of these therapies in adequately powered clinical trials.

Predictors of adherence to prescribed antihypertensive medications among Hypertensive (15-49 years) in India: A secondary data analysis of National Family Health Survey 4.

Background: Adherence to medications is one of the key determinants of therapeutic control of high blood pressure and is seen as a bottleneck in our fight against hypertension control. We have little scientific evidence from India that highlights the determinants of treatment adherence. Aim: The purpose of this study was to identify the predictor adherence to the currently prescribed antihypertensive medications. Material and Methods: We did a secondary data analysis of the National Family Health Survey, 2015-2016 datasets. As there were no direct variables to measure adherence, this was derived from the responses to the survey question: "currently taking a prescribed hypertensive medication to lower Blood Pressure" among those already diagnosed as hypertensives by the physician. The other sociodemographic and household-level variables were used as independent variables for analysis. Results: The level of awareness about their hypertensive status among the 15-49-year-olds who were subjected to blood pressure measurement was 9.34% (70,267/80,3081). Of these, 70,267 participants, 65878 with valid hypertensive individual data were included in the final analysis. Among them, 26.78% are currently adhering to antihypertensive medication. Female gender (adj OR; 95% CI: 1.17 [1.09-1.24]) and non-reserved caste ([OR] 1.24; 95% [CI]: 1.18-1.32) depicted better adherence to the current treatment. The hypertensives who preferred taking treatment from shops or at home or some other place in comparison to health facilities had a significant association with adherence (adj OR: 1.64; 95% CI: [1.43-1.88]). Conclusion: The current study reported low adherence to the current antihypertensive medication. Gender, higher age group, obesity, and place of taking the treatment were strongly associated with adherence to treatment.

Post-Electric Current Treatment Approaching High-Performance Flexible n-Type Bi2Te3 Thin Films.

Inorganic n-type Bi2Te3 flexible thin film, as a promising near-room temperature thermoelectric material, has attracted extensive research interest and application potentials. In this work, to further improve the thermoelectric performance of flexible Bi2Te3 thin films, a post-electric current treatment is employed. It is found that increasing the electric current leads to increased carrier concentration and electric conductivity from 1874 S cm−1 to 2240 S cm−1. Consequently, a high power factor of ~10.70 µW cm−1 K−2 at room temperature can be achieved in the Bi2Te3 flexible thin films treated by the electric current of 0.5 A, which is competitive among flexible n-type Bi2Te3 thin films. Besides, the small change of relative resistance <10% before and after bending test demonstrates excellent bending resistance of as-prepared flexible Bi2Te3 films. A flexible device composed of 4 n-type legs generates an open circuit voltage of ~7.96 mV and an output power of 24.78 nW at a temperature difference of ~35 K. Our study indicates that post-electric current treatment is an effective method in boosting the electrical performance of flexible Bi2Te3 thin films.

TreatmentPatterns: An R package to facilitate the standardized development and analysis of treatment patterns across disease domains.

BACKGROUND AND OBJECTIVES: There is an increasing interest to use real-world data to illustrate how patients with specific medical conditions are treated in real life. Insight in the current treatment practices helps to improve and tailor patient care, but is often held back by a lack of data interoperability and a high-level of required resources. We aimed to provide an easy tool that overcomes these barriers to support the standardized development and analysis of treatment patterns for a wide variety of medical conditions. METHODS: We formally defined the process of constructing treatment pathways and implemented this in an open-source R package TreatmentPatterns (https://github.com/mi-erasmusmc/TreatmentPatterns) to enable a reproducible and timely analysis of treatment patterns. RESULTS: The developed package supports the analysis of treatment patterns of a study population of interest. We demonstrate the functionality of the package by analyzing the treatment patterns of three common chronic diseases (type II diabetes mellitus, hypertension, and depression) in the Dutch Integrated Primary Care Information (IPCI) database. CONCLUSION: TreatmentPatterns is a tool to make the analysis of treatment patterns more accessible, more standardized, and more interpretation friendly. We hope it thereby contributes to the accumulation of knowledge on real-world treatment patterns across disease domains. We encourage researchers to further adjust and add custom analysis to the R package based on their research needs.

A-site deficient La0.52Sr0.28Ti0.94Ni0.06O3by low-pulsed electric current treatment: achieved exsolution of B-site Ni nanoparticles and significant improvement of electrocatalytic properties.

Perovskite materials with exsolved nanoparticles have a wide range of applications in energy conversion systems owing to their unique basal plane active sites and excellent catalytic properties. The introduction of A-site deficiency can help the formation of highly mobile oxygen vacancies and remarkably enhance the reducibility of Ni nanoparticles, thus significantly increasing electronic conductivity and catalytic activity simultaneously. Herein, we adopt pulsed electric current (PEC) treatment, a novel approach instead of the long-time high-temperature reduction technique, and for the first time review that the exsolution of minuscule Ni nanoparticles (8-20 nm) could be facilitated on Ni-doped La0.52Sr0.28Ti0.94Ni0.06O3(LSTN) anodes with A-site deficiency. Encouragingly, finding that low PEC can successfully lead to nanoparticle exsolution and show a significantly improved oxygen evolution reaction performance of LSTN-PEC (LSTN after PEC treatment) possessing A-site deficiency, the onset potential of LSTN-PEC (500 V) (LSTN after PEC treatment with 500 V-4 Hz-90 s) was advanced by 0.173 V, theRctvalue was reduced by 82.38 Ω·cm2, and the overpotential was also reduced by 73 mV.

Emerging Therapeutic Landscape of Peripheral T-Cell Lymphomas Based on Advances in Biology: Current Status and Future Directions.

T-cell lymphomas are a relatively rare group of malignancies with a diverse range of pathologic features and clinical behaviors. Recent molecular studies have revealed a wide array of different mechanisms that drive the development of these malignancies and may be associated with resistance to therapies. Although widely accepted chemotherapeutic agents and combinations, including stem cell transplantation, obtain responses as initial therapy for these diseases, most patients will develop a relapse, and the median survival is only 5 years. Most patients with relapsed disease succumb within 2 to 3 years. Since 2006, the USFDA has approved five medications for treatment of these diseases, and only anti-CD30-therapy has made a change in these statistics. Clearly, newer agents are needed for treatment of these disorders, and investigators have proposed studies that evaluate agents that target these malignancies and the microenvironment depending upon the molecular mechanisms thought to underlie their pathogenesis. In this review, we discuss the currently known molecular mechanisms driving the development and persistence of these cancers and discuss novel targets for therapy of these diseases and agents that may improve outcomes for these patients.

Risk factor, diagnosis, and current treatment of H. pylori Infection in Indonesia: A Literature Review.

Helicobacter pylori (H. pylori) infection has become an emerging problem in Indonesia despite its relatively low prevalence as opposed to other Southeast Asian and Asian countries. Strains containing less virulent genotypes predominantly found in Indonesia is suggested to be the rationale for why the disease prevalence, as well as its gastric cancer complication, remain inferior in respect of neighboring counterparts. Although endoscopic evaluation is still necessary to determine the gastric mucosal status of those infected with H. pylori, the infection itself can be easily diagnosed with test-and-treat strategy especially in areas with limited resources. Several findings revealed high rates of antibiotic resistance varying among Indonesian regions and ethnicities, suggesting that triple therapy regimen may not be suitable for all population. Whereas treatment should be based on the pattern of resistance in respected region, novel regimens involving furazolidone, rifabutin, and sitafloxacin are proposed as potential drugs of choice to eradicate H. pylori infection. In order to determine the adequate approach for H. pylori infection in Indonesia, further multicenter studies involving larger sample size should be conducted.

Projecting the long-term benefits of single pill combination therapy for patients with hypertension in five countries.

OBJECTIVE: To project the 10-year clinical outcomes associated with single pill combination (SPC) therapies compared with multi-pill regimens for the management of hypertension in five countries (Italy, Russia, China, South Korea and Mexico). METHODS: A microsimulation model was designed to project health outcomes between 2020 and 2030 for populations with hypertension managed according to four different treatment pathways: current treatment practices (CTP), single drug with dosage titration then sequential addition of other agents (start low and go slow, SLGS), free choice combination with multiple pills (FCC) and combination therapy in the form of a single pill (SPC). Model inputs were derived from the Global Burden of Disease 2017 dataset. Simulated outcomes of mortality, chronic kidney disease (CKD), stroke, ischemic heart disease (IHD), and disability-adjusted life years (DALYs) were estimated for 1,000,000 patients on each treatment pathway. RESULTS: SPC therapy was projected to improve clinical outcomes over SLGS, FCC and CTP in all countries. SPC reduced mortality by 5.4% in Italy, 4.9% in Russia, 4.5% in China, 2.3% in South Korea and 3.6% in Mexico versus CTP and showed greater reductions in mortality than SLGS and FCC. The projected incidence of clinical events was reduced by 11.5% in Italy, 9.2% in Russia, 8.4% in China, 4.9% in South Korea and 6.7% in Mexico for SPC versus CTP. CONCLUSIONS: Ten-year projections indicated that combination therapies (FCC and SPC) are likely to reduce the burden of hypertension compared with conventional management approaches, with SPC showing the greatest overall benefits due to improved adherence.

Weak Electric Current Treatment to Artificially Enhance Vascular Permeability in Embryonated Chicken Eggs.

Technologies that overcome the barrier presented by vascular endothelial cells are needed to facilitate targeted delivery of drugs into tissue parenchyma by intravenous administration. We previously reported that weak electric current treatment (ET: 0.3-0.5 mA/cm2) applied onto skin tissue in a transdermal drug delivery technique termed iontophoresis induces cleavage of intercellular junctions that results in permeation of macromolecules such as small interfering RNA and cytosine-phosphate-guanine (CpG) oligonucleotide through the intercellular space. Based on these findings, we hypothesized that application of ET to blood vessels could promote cleavage of intercellular junctions that artificially induces increase in vascular permeability to enhance extravasation of drugs from the vessels into target tissue parenchyma. Here we investigated the effect of ET (0.34 mA/cm2) on vascular permeability using embryonated chicken eggs, which have blood vessels in the chorioallantoic membrane (CAM), as an animal model. ET onto the CAM of the eggs significantly increased extravasation of intravenously injected calcein (M.W. 622.6), a low molecular weight compound model, and the macromolecule fluorescein isothiocyanate (FITC)-dextran (M.W. 10000). ET-mediated promotion of penetration of FITC-dextran through vascular endothelial cells was also observed in transwell permeability assay using monolayer of human umbilical vein endothelial cells without induction of obvious cellular damage. Confocal microscopy detected remarkable fluorescence derived from injected FITC-dextran in blood vessel walls. These results in embryonated chicken eggs suggest that ET onto blood vessels could artificially enhance vascular permeability to facilitate extravasation of macromolecules from blood vessels.

Crystalline and Electrical Property Improvement of Filtrated, Exfoliated Graphite Sheets by an In-Plane Current and Heating Treatment.

We report an approach to fabricate high conductivity graphite sheets based on a heat-and-current treatment of filtrated, exfoliated graphite flakes. This treatment combines heating (~ 900 °C) and in-plane electrical current flow (550 A·cm-2) to improve electrical conductivity through the reduction of crystalline defects. This process was shown to require only a 1-min treatment time, which resulted in a 2.1-fold increase in electrical conductivity (from 1088 ± 72 to 2275 ± 50 S·cm-1). Structural characterization by Raman spectroscopy and X-ray diffraction indicated that the improvement electrical conductivity originated from a 30-fold improvement in the crystallinity (Raman G/D ratio increase from 2.8 to 85.3) with no other observable structural transformations. Significantly, this treatment was found to act uniformly across a macroscopic (10 mm) sheet surface indicating it is on the development of applications, such as electrodes for energy generation and storage and electromagnetic shielding, as well as on the potential for the development of large-scale treatment technologies.

Understanding underactive bladder: a review of the contemporary literature.

Underactive bladder (UAB) is characterized by prolonged voiding, hesitancy, and slow and/or intermittent stream with or without a sensation of incomplete bladder emptying. The overlap of UAB lower urinary tract symptoms with those of overactive bladder or bladder outlet obstruction, as well as its multifactorial etiology, make UAB study, as well as its diagnosis and management, a very arduous and challenging task. Therefore, despite its incidence and significant impact in the quality of life of both men and women, UAB remains a poorly understood urologic condition with insufficient and ineffective treatment options available. In this review, we will focus on the etiology theories that have been proposed and the animal models available to test those theories.

Coronavirus as silent killer: recent advancement to pathogenesis, therapeutic strategy and future perspectives.

The present outbreak associated with corona virus [CoVs] in China which is believed to be one of the massive eruptions towards mankind in 2019-2020. In the present scenario CoVs has been transmitted to the European and American regions through the travellers from wide spread countries like China and Japan. The viral disease is spreading through the contact in any form by the infected persons or patients and creating huge risk of mortality. CoVs are a single positive-sense RNA virus; mutation rates are higher than DNA viruses and indicate a more effective survival adaption mechanism. Human CoVs can cause common cold and influenza-like illness and a variety of severe acute respiratory disease such as pneumonia. Early in infection, CoVs infects epithelial cells, macrophages, T-cells, dendritic cells and also can affect the development and implantation of pro-inflammatory cytokines and chemokines. It mainly produces the melanoma differentiation associated with protein-5, retinoic acid inducible gene-1 and endosomal toll-like receptor 3. How CoVs affects the function of the immune system is still unclear due to lack of this knowledge. No Food and Drug Administration approved treatment is available till date. In this review, we are tried to explore the epidemiology, pathogenesis and current treatment of CoVs infection. The promising therapeutics molecules against CoVs and future prospective have been also discussed which will be helpful for researchers to find out the new molecules for the treatment of CoVs disease.