Clinical actionability

Homologous recombination (HR) related gene alterations are present in a significant subset of prostate, breast, ovarian, pancreatic, lung and colon cancers rendering these tumors as potential responders to specific DNA damaging agents. A small molecule acylfulvene prodrug, LP-184, metabolizes to an active compound by the oxidoreductase activity of enzyme Prostaglandin Reductase 1 (PTGR1), which is frequently elevated in multiple solid tumor types. Prior work demonstrated that cancer cell lines deficient in a spectrum of (DNA damage repair) DDR pathway genes show increased susceptibility to LP-184...

Contrary to North America and Europe, the prevalence of hypertension is rising in West Africa. With a transition from whole foods to processed foods in Nigeria, diet plays a key driver of hypertension. To combat this, the national nutritional guidelines in Nigeria were implemented, but their translation into actionable tools for clinicians remains a challenge. Currently, there are no simple dietary assessment tools that are concise and suitable to be incorporated into clinical care without requiring extensive data analysis while still providing personalised dietary support to their patients...

In recent years, mouse nerve growth factor (mNGF) has emerged as an important biological regulator to repair peripheral nerve injury, but its systemic application is restricted by low efficiency and large dosage requirement. These limitations prompted us to search for biomaterials that can be locally loaded. Oxidized sodium alginate hydrogel (OSA) exhibits good biocompatibility and physicochemical properties, and can be loaded with drugs to construct a sustained-release system that can act locally on nerve injury...

Genomic epidemiology enhances the ability to detect and refute methicillin-resistant Staphylococcus aureus (MRSA) outbreaks in healthcare settings, but its routine introduction requires further evidence of benefits for patients and resource utilization. We performed a 12 month prospective study at Cambridge University Hospitals NHS Foundation Trust in the UK to capture its impact on hospital infection prevention and control (IPC) decisions. MRSA-positive samples were identified via the hospital microbiology laboratory between November 2018 and November 2019...

Spinal cord injury (SCI) usually induces profound microvascular dysfunction. It disrupts the integrity of the blood-spinal cord barrier (BSCB), which could trigger a cascade of secondary pathological events that manifest as neuronal apoptosis and axonal demyelination. These events can further lead to irreversible neurological impairments. Thus, reducing the permeability of the BSCB and maintaining its substructural integrity are essential to promote neuronal survival following SCI. Tetramethylpyrazine (TMP) has emerged as a potential protective agent for treating the BSCB after SCI...

BACKGROUND: The COVID-19 pandemic has sharpened the focus on health care safety and quality, underscoring the importance of using standardized metrics such as the International Classification of Diseases, Tenth Revision (ICD-10). In this regard, the ICD-10 cluster Y62-Y69 serves as a proxy assessment of safety and quality in health care systems, allowing researchers to evaluate medical misadventures. Thus far, extensive research and reports support the need for more attention to safety and quality in health care...

BACKGROUND: The use of hemostatic agents by general surgeons during abdominal operations is commonplace as an adjunctive measure to minimize risks of postoperative bleeding and its downstream complications. Proper selection of products can be hampered by marginal understanding of their pharmacokinetics and pharmacodynamics. While a variety of hemostatic agents are currently available on the market, the choice of those products is often confusing for surgeons. This paper aims to summarize and compare the available hemostatic products for each clinical indication and to ultimately better guide surgeons in the selection and proper use of hemostatic agents in daily clinical practice...

The heart beats are due to the synchronized contraction of cardiomyocytes triggered by a periodic sequence of electrical signals called action potentials, which originate in the sinoatrial node and spread through the heart's electrical system. A large body of work is devoted to modeling the propagation of the action potential and to reproducing reliably its shape and duration. Connection of computational modeling of cells to macroscopic phenomenological curves such as the electrocardiogram has been also intense, due to its clinical importance in analyzing cardiovascular diseases...

Adolphe Quételet, a 19th-century Belgian sociologist and statistician, pioneered the incorporation of statistics into social sciences. He initiated the development of anthropometry since he was interested in identifying the proportions of the 'ideal man'. He devised a ratio between weight and height, originally termed the Quételet Index, and today widely known and used as the body mass index or BMI. In 1835, he demonstrated that a normal curve accommodates the distribution of human traits articulating his reasoning on human variance around the average...

OBJECTIVE: To describe the organization of specialized outpatient clinics, according to the Secondary Outpatient Care Unit (SOCU) model according to the health care planning (HCP) methodology. METHODS: This is a descriptive and cross-sectional study, which used secondary data from the PlanificaSUS project. It was carried out in 16 outpatient clinics specialized in maternal and child care, distributed in the five Brazilian geographic regions. A structured questionnaire was used for self-assessment on the implementation of 12 parameters in two moments, in 2019 and in 2020...

Cisplatin is widely employed in clinical oncology as an anticancer chemotherapy drug in clinical practice and is known for its severe ototoxic side effects. Prior research indicates that the accumulation of reactive oxygen species (ROS) plays a pivotal role in cisplatin's inner ear toxicity. Hesperidin is a flavanone glycoside extracted from citrus fruits that has anti-inflammatory and antioxidant effects. Nonetheless, the specific pharmacological actions of hesperidin in alleviating cisplatin-induced ototoxicity remain elusive...

Covering: 1970 through June of 2023Verticillins are epipolythiodioxopiperazine (ETP) alkaloids, many of which possess potent, nanomolar-level cytotoxicity against a variety of cancer cell lines. Over the last decade, their in vivo activity and mode of action have been explored in detail. Notably, recent studies have indicated that these compounds may be selective inhibitors of histone methyltransferases (HMTases) that alter the epigenome and modify targets that play a crucial role in apoptosis, altering immune cell recognition, and generating reactive oxygen species...

Objective: To explore associations between maternal characteristics and recall of obstetric provider actions in promoting antepartum tetanus-diphtheria-acellular-pertussis (Tdap) vaccination. Methods: A convenience sample of 1,682 postpartum women was surveyed in this cross-sectional study. Maternal characteristics and recall of four obstetric provider actions (recommending antepartum Tdap vaccine, offering it in clinic, providing written information, and referring patients elsewhere for vaccination) were collected...

INTRODUCTION: Epilepsy is a chronic neurological condition characterized by a persistent propensity for seizure generation. About one-third of patients do not achieve seizure control with the first-line treatment options, which include > 20 antiseizure medications. It is therefore imperative that new medications with novel targets and mechanisms of action are developed. AREAS COVERED: Clinical studies and preclinical research increasingly implicate Non-receptor tyrosine kinases (nRTKs) in the pathogenesis of epilepsy...

BACKGROUND: Diosmetin is an O-methylated flavone and the aglycone part of the flavonoid glycosides diosmin that occurs naturally in citrus fruits. Pharmacologically, diosmetin is reported to exhibit anticancer, antimicrobial, antioxidant, oestrogenic, and anti-inflammatory activities. OBJECTIVE: This comprehensive review was aimed to critically explore diverse pharmacological activities exhibited by diosmetin. Along with that, this review can also identify potential research areas with an elucidation of the multifactorial underlying signaling mechanism of action of diosmetin in different diseases...

The landscape of cancer therapy has witnessed a paradigm shift with the emergence of innovative delivery systems, and Guanidinium-based Peptide Dendrimers have emerged as a vanguard in this transformative journey. With their unique molecular architecture and intrinsic biocompatibility, these dendrimers offer a promising avenue for the targeted delivery of therapeutic cargo in cancer treatment. This comprehensive review delves into the intricate world of Guanidinium- based Peptide Dendrimers, unraveling their structural intricacies, mechanisms of action, and advancements that have propelled them from laboratory curiosities to potential clinical champions...

BACKGROUND: Selective serotonin reuptake inhibitors (SSRIs) are first-line pharmacological treatments for depression and anxiety. However, little is known about how pharmacological action is related to cognitive and affective processes. Here, we examine whether specific reinforcement learning processes mediate the treatment effects of SSRIs. METHODS: The PANDA trial was a multicentre, double-blind, randomized clinical trial in UK primary care comparing the SSRI sertraline with placebo for depression and anxiety...

BACKGROUND: There is a growing, global awareness and recognition of the important, interdependent relationships between our natural world and human health. Several contemporary health organizations have placed calls to action and emphasize an urgent need for collaboration and interdisciplinary research, education, and clinical work to address the increasing degradation of our planetary and human health. With more research dedicated to nature's health impacts, health professions schools would benefit by including such training in their programs while also cultivating a comprehensive mind-body health perspective to support both the health of student practitioners and their future patients...

BACKGROUND: The recovery of upper extremity motor impairment after stroke remains a challenging task. The clinical effectiveness of repetitive transcranial magnetic stimulation (rTMS), which is believed to aid in the recovery process, is still uncertain. METHODS: A systematic search was conducted in Medline (Ovid), Cochrane and Embase electronic databases from March 28, 2014, to March 28, 2023. The inclusion criteria consisted of randomized controlled trials that assessed the effects of rTMS on the recovery of upper limb motor impairment among stroke patients...

Melasma is a chronic hyperpigmentation skin disorder that is more common in the female gender. Although melasma is a multifactorial skin disorder, however, sun-exposure and genetic predisposition are considered as the main etiologic factors in melasma occurrence. Although numerous topical and systemic therapeutic agents and also non-pharmacologic procedural treatments have been considered in melasma management, however, the commonly available therapeutic options have several limitations including the lack of sufficient clinical effectiveness, risk of relapse, and high rate of unwanted adverse drug reactions...