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After establishing the new standard of care of isotonic fluids for maintenance therapy, there has not been a systematic follow-up to determine whether the goal of the switch has been achieved or whether there have been any unexpected complications with the change. This is a brief review of the history of maintenance intravenous fluids and potential complications of isotonic fluid therapy spurred by a case.

In children, the global burden of vaccines-preventable diseases (VPDs) and deaths can be averted by adopting timely immunization practices. Administering immunization to a child within 28 or 30 days of the designated immunization date is referred to as timely immunization. Besides timely immunization, immunization non-compliance (invalid or delayed or missed immunization) increases the risk of various forms of VPDs and death in children, particularly living in urban slums. 

Pancreatic β cell dysfunction is an important cause of type 2 diabetes (T2D). Previous studies show trimethylamine N-oxide (TMAO), a gut microbiota-related metabolite, promotes cardiovascular disease and insulin resistance. However, the effect and mechanism of TMAO at pathological concentrations on β cell function remain unknown. The recently published work demonstrates TMAO reduces pancreatic β cell function and glucose homeostasis.

Support for stem cell self-renewal and differentiation hinges upon the intricate microenvironment termed the stem cell 'niche'. Within the adipose tissue stem cell niche, diverse cell types, such as endothelial cells, immune cells, mural cells, and adipocytes, intricately regulate the function of adipocyte precursors. These interactions, whether direct or indirect, play a pivotal role in governing the balance between self-renewal and differentiation of adipocyte precursors into adipocytes. 

Early-stage NSCLC, encompassing resectable stage I-III  are curable, and represents 25% of all lung cancers. The management of non-metastatic NSCLC is a rapidly changing area of clinical oncology, where utilization of molecular biomarkers has become a cornerstone in informing appropriate management. In current clinical practice, adjuvant chemotherapy is recommended after surgical resection for tumors ≥ 4 cms in size (AJCC 7th stage IB, AJCC 8th stage IIA, and higher stage groups thereafter).

Background: Chikungunya virus (CHIKV) is an alphavirus spread by mosquitos that causes arthralgias and arthritis that may last for years. The objective of this study was to describe the arthritis progression and T cell immunology over a two-year period. Methods: A cohort of 40 cases of serologically confirmed CHIKV from Magdalena and Atlántico, Colombia were followed in 2019 and again in 2021. Arthritis disease severity, disability, pain, stiffness, physical function, mobility, fatigue, anxiety, sleep disturbances and depression were assessed. 

Objectives: Here, we review opioid-sparing or opioid-free anesthesia and pain management for urologic procedures and pathologies–urological pain syndromes, kidney stone pain management, development of post-surgical pain syndromes, and prevention. We explore acute management of perioperative pain during and after urologic procedures; additionally, we review the pathophysiology of various urologic pain syndromes along with a variety of interventions, including pharmacologic management, nerve blocks, neurolysis, and neuromodulatory therapies in hopes of educating providers who treat the urologic patient.

Chimeric antigen receptor (CAR)-T cell therapy has shown potential in improving outcomes for individuals with hematological malignancies. However, achieving long-term full remission for blood cancer remains challenging due to severe life-threatening toxicities such as limited anti-tumor efficacy, antigen escape, trafficking restrictions, and limited tumor invasion. Furthermore, the interactions between CAR-T cells and their host tumor microenvironments have a significant impact on CAR-T function.

The emergence of chimeric antigen receptor T cell (CAR-T cell) therapy has revolutionized cancer treatment, particularly for hematologic malignancies. This commentary discusses developments in CAR-T cell therapy, focusing on the molecular mechanisms governing T cell fate and differentiation. Transcriptional and epigenetic factors play a pivotal role in determining the specificity, effectiveness, and durability of CAR-T cell therapy.

In the quest for improving the clinical outcome of patients with metastatic genitourinary cancers, including metastatic renal cell carcinoma (mRCC), the emphasis often is on finding new targeted therapies. However, two studies by Jordan et al. (Oncogenesis 2020) and Wang et al. (Cancer Cell Int 2022) demonstrate the feasibility of improving the efficacy of a modestly effective drug Sorafenib against mRCC by attacking a mechanism hijacked by RCC cells for inactivating Sorafenib.

This review underscores the important role of nutrition in enhancing the management of Human Immunodeficiency Virus type 1 (HIV-1). Highlighting the efficacy of dietary interventions, including, the importance of omega-3 fatty acids, vitamins D and B-12, and the Mediterranean diet, we delineate how these beneficial nutritional strategies can improve the effectiveness of combined antiretroviral therapy (cART), mitigate its side effects, and ameliorate metabolic disorders in people living with HIV-1 (PLWH). 

The role of inflammation has been accepted as a factor in the complications of diabetic retinopathy. Discovery of the upstream regulation of these inflammatory factors has remained a challenge. In this study, we explored the actions of ephrin B1 in retinal Müller cells and their actions on inflammatory proteins. We used diabetic human and mouse samples, as well as Müller cells in culture to measure ephrin B1 in Müller cells.

α6-containing GABA_A receptors (α6GABA_ARs) are strongly expressed in cerebellar granule cells, where they mediate a correctly timed and precise coordination of all muscle groups that execute behavior and protect the brain from information overflow. Recently, it was demonstrated that positive modulators with a high selectivity for α6GABA_ARs (α6-modulators) can reduce the symptoms of multiple neuropsychiatric disorders in respective animal models to an extent comparable with established clinical therapeutics.

Mitochondrial dysfunction underlines neurodegenerative diseases which are mostly characterized by progressive degeneration of neurons. We previously reported that Cellular retinoic acid Binding protein 1 (Crabp1) knockout (CKO) mice spontaneously developed age-dependent motor degeneration, with defects accumulated in spinal motor neurons (MNs), the only cell type in spinal cord that expresses CRABP1.

Excessive food intake leads to lipid accumulation in white adipose tissue, triggering inflammation, cellular stress, insulin resistance, and metabolic syndrome. In contrast, the dynamic energy expenditure and heat generation of brown and beige adipose tissue, driven by specialized mitochondria, render it an appealing candidate for therapeutic strategies aimed at addressing metabolic disorders.

Background: Adolescents with mental disorders often have difficulty engaging in ongoing treatment. Dropout from treatment is common. Aim: This paper aims to explore the clinical characteristics of a cohort of adolescents with mental disorders who were stably and actively undergoing psychotherapy over a relatively long period of time (for at least four months).

Similar to other African countries, life expectancy of people living with HIV infection has improved due to access to antiretroviral therapy (ART) in Rwanda. However, both HIV infection and use of ART are associated with cardiovascular disease (CVD) risks, due to adverse changes in some biomarkers, causing dyslipidemia and other metabolic imbalances. Biomarkers for CVD risk in HIV-infected individuals taking ART, has not been well characterized in Rwanda.

The dissemination of the extended spectrum β-lactamases (ESBL) producing E. coli poses a significant public health problem. Understanding the efficiency and frequency of horizontal gene transfer via conjugation of ESBL producing E. coli is imperative towards devising prevention and control measures. This study compared the frequencies and efficiencies of horizontal bla_CTX-M gene transfer via conjugation among Escherichia coli isolates from urine and gastrointestinal tract (GIT) of patients with urinary tract infection (UTI), their animals and environment.

This is the first reported case of COVID-19 associated optic neuritis (ON) presenting with classic Uhtoff’s phenomenon typically associated with multiple sclerosis (MS). Uhthoff phenomenon, also known as Uhthoff sign or syndrome, is a transient worsening of neurological function lasting less than 24 hours that can occur in multiple sclerosis patients due to increases in core body temperature.

Venetoclax, a small-molecule B-cell lymphoma 2 (BCL-2) inhibitor, selectively eradicates leukemic stem cells (LSCs). While venetoclax has revolutionized the treatment of acute myeloid leukemia (AML), treatment failure and disease relapse are common. Mechanisms underlying venetoclax resistance are surprisingly heterogeneous.

Background: While medications for opioid use disorder (MOUD) reduce overdose risk, inconsistent use can lead to substance use recurrence and compromise achieving optimal opioid use disorder (OUD) treatment outcomes. Research is limited on patient-reported perspectives on consistency of MOUD self-administration at home and its related social factors.

Inorganic microparticles are ubiquitous in the modern Western diet present as food additives and are actively scavenged by microfold (M) cells overlying human intestinal lymphoid aggregates. In Crohn’s disease (CD), inflammation is caused by the inability of the intestinal mucosa to sustain tolerance to gut luminal factors including bacteria and their by-products.

Oxidative stress (OS) in the airway epithelium is associated with inflammation, cell damage, and mitochondrial dysfunction that may initiate or worsen respiratory disease. Redox regulation maintains the equilibrium of pro-oxidant/antioxidant reactions but can be disturbed by environmental exposures. The mechanism(s) underlying the induction and impact of OS on airway epithelium and how these influences on respiratory disease is poorly understood.

Oxidative stress (OS) in the airway epithelium is associated with cell damage, inflammation, and mitochondrial dysfunction that may initiate or worsen respiratory disease. However, it is unclear whether exogenous antioxidants can provide protection to the airway epithelium from OS. Resveratrol and astaxanthin are nutritional compounds that have shown diverse benefits including protection against OS and inflammation in various situations.

Rib fractures are a commonly encountered traumatic injury and are associated with significant morbidity and mortality. They are a marker of severe injury and can lead to defects in the chest wall and severe pain which may hinder breathing.

The COVID-19 pandemic has made the development of novel vaccines a high priority for public health. While many vaccines have focused on the generation of neutralizing antibodies, we have discovered a novel herpes simplex virus (HSV) vaccine candidate, designated ΔgD-2, that can preferentially elicit non-neutralizing antibodies that function through Fcγ receptor (FcγR) activation

The COVID-19 pandemic is associated with a large number of patients spending long periods of time in intensive care units (ICUs), many of them suffering bacterial/fungal superinfections. However, both the incidence and cause of bacterial/fungal superinfections in COVID-19 critically ill patients remain poorly investigated in hospitals located at high altitudes (above 2500 meters).

Autism spectrum disorder (ASD) prevalence has increased year on year for the past two decades and currently affects 1 in 44 individuals in the US. An increasing number of studies have pointed to increased immune activation as both an etiological agent and also involved in the ongoing pathological process of ASD. Both adaptive and innate immune responses have been implicated. Evidence of innate dysregulation has so far included increased production of innate inflammatory cytokines, increased cell numbers, and altered activation in monocytes in the blood and microglia in the brain.

In their recent article, “Jail-Based Competency Treatment Comes of Age,” Jennings et al. [1] reviewed the historical development of the model and presented the first large-scale empirical support for its effectiveness, which covered eight years of outcomes across four different program sites for nearly 2,000 Incompetent to Stand Trial (IST) defendants.

The adoptive transfer of T cells expressing chimeric antigen receptors (CAR-T cells) has revolutionized the treatment of hematological malignancies, providing unmatched clinical responses in adults and children with relapsed or refractory B cell malignancies.

At initial (basic) training recruits from all services and most nations are subject to an intense environment where they are physically and mentally challenged throughout their waking day. Their civilian experiences and identity are systematically remodeled to fit the requirements of the nation’s services. Most recruits are able to cope with this extreme environment, albeit with some impact on their mental wellbeing, whereas those unable to cope either physically or emotionally are discharged from the Military through medical or administrative procedures.

Langerhans cell histiocytosis (LCH) is a rare, clonal, haematological disease of myeloid origin involving infiltration of neoplastic cells resembling Langerhans cells in various tissues. LCH cells express normal Langerhans cell markers such as CD1a, Langerin (CD207), and S100.

Teeth together with supporting periodontium are continuously under physical stimulation in daily life and clinical dental situations. Physical stimulation plays an important role in oral health. However, the underlying molecular pathways by which physical stimulation preserves oral health remain unknown.

Diabetes is a chronic disorder that affects more than 500 million individuals worldwide. It is a life-long disease with complications that attack nearly all other systems within the body. Although there is a slight increase in the prevalence of diabetes in males, ocular surface complications are equally present in males and females.

Imatinib is a selective inhibitor of the bcr-abl tyrosine kinase making it a potential treatment of chronic myelogenous leukemia (CML), as well as a selective inhibitor of KIT protein tyrosine kinase, and PDGF receptor, and is the treatment of choice in patients with gastrointestinal stromal tumors (GISTs)

The term Proprioceptive Neuromuscular Facilitation (PNF) was introduced in the 1950s by Dr. Kabat and Mrs. Knott. From the mid-1950s the PNF-concept has been in a progressive development clarifying the use of techniques, performances and clinical applications. The concept of PNF was originally developed by Dr. Kabat and Mrs. Knott for rehabilitation purposes. The International PNF Association (IPNFA) consider themselves to be the official successor of Dr. Kabat and Mrs. Knott.

Sepsis is a key driver of worldwide mortality, representing close to 20% of global deaths in 2017 [1]. Approximately half of patients hospitalized with sepsis are 65 years and older [2]. Delivery of 30ml/kg of crystalloid fluid bolus within three hours of diagnosing sepsis remains a cornerstone of the Surviving Sepsis Campaign (SSC)

Multiple myeloma (MM) is a common hematologic malignancy, with 32,110 new cases diagnosed in the United States in 2019, resulting in 12,960 deaths. While neutrophilia
is also a common entity, it most often arises secondary to other etiologies, such as infection or inflammatory processes. 

The contribution of β3-AR activation towards ischemiareperfusion (IR) damage largely depends on the disease stage, severity, experimental model as well as drug specificities which should be considered when investigating β3-AR pharmacology for potential therapeutic applications. These conceptions largely contribute to the discrepancies of the subsequent role of β3-AR activation in the cardiovascular disease process. 

A role for oxidative stress in the etiology of myriad neuropathologies is well accepted. However, the specific effects of oxidative DNA damage in the onset or promotion of neuronal dysfunction have been less studied. In our recent publication by Behrouzi et al. (Oxidative DNA Damage and Cisplatin Neurotoxicity Is Exacerbated by Inhibition of OGG1 Glycosylase Activity and APE1 Endonuclease Activity in Sensory Neurons), inhibition of enzymes that play a role in repairing oxidative DNA damage exacerbated neurotoxic effects of the chemotherapeutic agent, cisplatin. 

Diastolic heart failure (DHF) is also be regarded as heart failure with preserved ejection fraction (HFpEF), is estimated to occur in 40 to 50% of patients with HF. More than 70% of HF patients over the age of 65 had HFpEF, and the incidence and prevalence of HFpEF has been increased by 10% every 10 years in comparison to HF with reduced ejection fraction (HFrEF), and this gap is expected to widen in the coming years.

Bladder cancer is the sixth most common malignancy in the United States and 70% of cases are non-muscle invasive at the time of diagnosis. Effective treatment is crucial to prevent progression, which occurs in about 30% of patients. The American Urological Association (AUA) guidelines recommend treatment of non-muscle invasive bladder cancer (NMIBC) with intravesical Bacille Calmette-Guerin (BCG) and chemotherapy.

The development of direct-acting antiviral agents for the treatment of Hepatitis C (HCV) has changed the practice of treating patients with HCV. In particular, organ transplant recipients who have not previously been exposed to HCV are now able to consider receiving an organ from a donor who is infected with HCV, and anticipate effective antiviral therapy after transplantation.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic affected Solid-Organ transplantation (SOT) policies and practices worldwide. The medical sector had to adapt to overwhelming concerns regarding patient care, infection-control, healthcare workers’ safety, and limited healthcare resources. Transplant-

The COVID-19 pandemic started at the end of 2019 and remains carrying a health threat and significant economic consequences. Over the last two years, COVID-19 has been the main Public Health issue, and has impacted regular healthcare systems, with significant build-up of waiting lists and delay in optimum management of other serious medical conditions including heart diseases and cancer.

Background: When the highest vaccine COVID-19 booster effectiveness (VBE) is obtained is not clearly known. Objective: To compare the cases of COVID-19 in booster vaccinated people with a time of <29 days vs. ≥ 29 days from booster to infection diagnosis and assess their relative VBE. Methodology: An observational, longitudinal and prospective case series study of adult patients with COVID-19 breakthrough infections in booster vaccinated people, in general medicine and for the period December 2021 to February 2022, during the omicron variant contagion wave.

Pulmonary embolism (PE) is a blockage of blood flow in the pulmonary artery bed that can result in a life-threatening and potentially reversible right ventricular failure [1]. PE remains one of the leading causes of poor prognosis and death, particularly when a shock or right ventricular failure occurs [2]. According to studies, PE is generally manifested in a nonspecific manner

HIV infection in pregnancy continues to be of significant clinical and public health importance [1,2]. The current statistics published by the World Health Organization (WHO) demonstrate that 38 million people are living with HIV in 2019, and 1.1 million (85%) pregnant women living with HIV received antiretroviral therapy (ARVs) during pregnancy and postpartum.

Sleep is an evolutionarily conserved phenomenon which has survived tremendous evolutionary pressures. Its disruption has deleterious implications for human health. The importance of sleep is illustrated by the fact that sleep deprivation in many animals leads to death. While sleep is tightly regulated by a combination of intrinsic and extrinsic factors it becomes progressively disrupted in old age and in neurodegenerative diseases including Alzheimer’s disease (AD), frontotemporal dementia (FTD), Parkinson’s disease (PD) and Huntington’s disease (HD). 

The first case is described in Wuhan city of China in December 2019 and the disease (COVID-19) continues to pose threat to global health all over the world affecting more than approximately 476 million confirmed cases and 6 million deaths. Reliable and effective methods are taken a critical role such as real-time reverse transcriptase (RT)-PCR test as a gold standard method, serological tests, and reverse transcriptase loopmediated isothermal amplification (RT-LAMP) method is chosen firstly. 

Approximately 1.6-3.8 million people sustain a mild traumatic brain injury (mTBI) in the US annually. This amounts to the hospitalization of 100-300 per 100,000 young adults. The Centers for Disease Control and Prevention reports that around 5.3 million people live with a permanent disability after mTBI, and there are currently no known restorative therapies.

Plant virus nanoparticles (PVNPs) are increasingly recognized and studied for use in biomedical applications. PVNPs include plant virions with self-assembled capsid protein coats (PC) that encapsulate the virus genome, and virus-like particles (VLPs), a capsid without the viral genome.

NOBOX is an ovarian specific transcription factor that plays an important role in follicular growth and survival. Nineteen NOBOX variants have been previously associated with premature ovarian insufficiency (POI). Disease severity in patients with heterozygous and homozygous mutations largely overlap however, hampering genotype-phenotype correlations. We recently reported the first case of biallelic truncating mutations (NM_001080413.3 (NOBOX):c.826C>T, p.(Arg276*) and NM_001080413.3(NOBOX):c.1421del, p.(Gly474Alafs*76)) of NOBOX in two Belgian sisters with POI.

Due to changes in end-stage renal disease (ESRD) policies in many countries and the impact of COVID-19, the importance and demand for peritoneal dialysis (PD) as a home dialysis treatment modality is growing prominently [1]. However, peritoneal membrane dysfunction remains a bottleneck restricting the application of PD. Therefore, there is an urgent need to develop new methods to accurately assess peritoneal function.

Bacterial communication via quorum sensing (QS) molecules, as well as toxin-antitoxin (TA) gene modules located on bacterial chromosomes are well-studied mechanisms. Escherichia coli mazEF is a stress-induced TA system mediating cell death requiring a QS extracellular death factor (EDF), the pentapeptide NNWNN. MazF is an endoribonuclease specific for ACA sites. During adverse conditions, the activated MazF generates a stress induced translation machinery, composed of MazF-processed mRNAs and selective ribosomes that specifically translate these processed mRNAs.

Balanced translocation resulting in fusion of the Abelson gene (ABL₁) from chromosome 9q34 with the breakpoint cluster region (BCR) gene on chromosome 22q11.2 is the pathognomonic molecular driver of CML. The resulting BCRABL 1 fusion gene is both the diagnostic as well as therapeutic target of CML. The first agent with tyrosine kinase inhibitor activity that was licenced in 2000 for treatment of CML patients, was Imatinib, gradually followed by multiple agents with higher efficacy.

Polycystic kidney disease is an inherited degenerative disease in which the uriniferous tubules are replaced by expanding fluid-filled cysts that ultimately destroy organ function. Autosomal dominant polycystic kidney disease (ADPKD) is the most common form, afflicting approximately 1 in 1,000 people and is caused by mutations in the transmembrane proteins polycystin-1 (Pkd1) and polycystin-2 (Pkd2).

Alzheimer’s disease (AD) research has long been dominated with communications regarding the amyloid hypothesis and targeting amyloid clearance through pharmacological therapies from the brain [1]. 

Perceptual thresholds might vary due to different variables such as fatigue, fluctuations of attention, or sensory learning [1]. Adaptive threshold estimation procedures are most effective by providing quasi-instantaneous estimates of an otherwise fluctuating sensory threshold. 

The Randomized intervention for Vesicoureteral Reflux (RiVUR) study was an effort by the National Institute of Health to identify the most significant question on the management of vesicoureteral reflux (VUR), i.e. Did antibiotic prophylaxis reduce the incidence of recurrent urinary tract infections (UTI) in children with VUR? During the initial phases of the RiVUR study, several similar studies were performed that seemed to indicate lack of benefit of antibiotic prophylaxis in VUR.

Phytophthora infestans is the causal agent of late blight disease, which affects potato and tomato crops worldwide, that brings about significant economic losses in the production of these crops. The PITG_06016 gene codes for one of the 7 glucokinases present in this phytopathogen.

The prevalence of many musculoskeletal and cardiovascular diseases that cause limitations in physical functioning has increased globally [1] with age-adjusted rates of incidence rising for many of these diseases [2-5]. In the United States alone, chronic health conditions that limit physical function have an estimated economic impact of $200

Inflammation drives prostate cancer (PCa) progression. While inflammation is a cancer hallmark, the underlying mechanisms mediating inflammation-induced PCa are still under investigation. Interleukin-1 (IL-1) is an inflammatory cytokine that promotes cancer progression, including PCa metastasis and castration resistance. We previously found that acute IL-1 exposure represses PCa androgen receptor (AR) expression concomitant with the upregulation of pro-survival proteins, causing de novo accumulation of castration-resistant PCa cells.

In 1989, researchers proposed an intricate strategy in the field of adoptive cell therapy (ACT). Using the T-cell receptor (TCR) as a template, they replaced the coding sequence for the Vα and Vβ chains with the antigen- recognition domains from an antibody (VH and VL chains).

Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that arises in the ventral pons during middle childhood. 

“Nothing was as it seemed. I was not as I seemed…I was confronted by the possibility that perhaps the truest thing about me was a coiled identity, my irrealis self, a might-have-been self that never really was but wasn’t unreal for not being and might still be real, though I feared it never would”

Alzheimer’s Disease (AD) and Alzheimer’s Disease-Related Dementias (ADRD) are debilitating conditions that are highly associated with aging populations, especially those with comorbidities such as diabetes and hypertension.

Cancer is a worldwide public health issue that affects millions of people every year. In 2018 there were 17 million newly documented cases of cancer globally (8.8 million in men and 8.2 million in women), leading to 9.6 million deaths. Cancer is a vastly heterogeneous disease, with over 100 different types of cancer currently identified in humans; the most common types of cancer are lung, female breast, bowel and prostate, these four types account for more than 40% of all new cancer case

Previously characterized as a purely immune mediated disease, sepsis is now recognized as a dysregulated multisystem response against a pathogen. Recognition of the infectious agent by pathogen recognition receptors (PRRs) can initiate activation of the NF-κB signaling pathway and promote the secretion of proinflammatory cytokines. During sepsis, the activation of NF-κB is dysregulated and results in cytokine storm, or the pathologic release of cytokines.

Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood.

Inhaled budesonide benefits patients with COVID-19. ProLung™-budesonide enables the sustained, low dose administration of budesonide within a delivery vehicle similar to lung surfactant.

Hepatocellular carcinoma (HCC) is a significant cause of cancer mortality worldwide. Chronic hepatic inflammation and fibrosis play a critical role in the development of HCC. Liver fibrosis develops as a result of response to injury such that a persistent and excessive wound healing response induces extracellular matrix (ECM) deposition leading to HCC.

The electron-dense spherical granules found in the perinuclear region of atrial myocytes store and release both proatrial and probrain natriuretic peptides (proANP and proBNP, respectively). Mature ANP and BNP produce vasodilation and natriuresis and inhibit the renin-angiotensin and sympathetic nervous systems.

Hydrogen peroxide (H₂O₂) is an important intra- and extra-cellular signaling molecule that can determine cell fate. At low concentrations, H₂O₂ plays roles in proliferation, immunity, and metabolism. Cellular exposure to higher non-physiologic concentrations of H₂O₂ can result in oxidative stress.

Cullin-RING E₃ ubiquitin ligase 4 (CRL₄) plays an essential role in cell cycle progression. Recent efforts using high throughput screening and follow up hit-to-lead studies have led to identification of small molecules 33-11 and KH-4-43 that inhibit E₃ CRL₄’s core ligase complex and exhibit anticancer potential.

Osmotic Demyelination Syndrome (ODS) is a unique process of selective demyelination and destruction of oligodendrocytes and astrocytes in specific areas of the brain that usually occurs a few days after an osmotic stress [1]. ODS has been described most frequently in association with a rapid correction of hyponatremia, though it may occur with other electrolyte or metabolic abnormalities.

The survival probability of early human conceptions is very low. At least 73% of natural single conceptions have no real chance of surviving six weeks of gestation [1]. After six weeks, survival rates improve rapidly as 90% of the remainder will survive to term.

The western diet and overuse of anti-inflammatory medication have caused a great deal of stress on the liver. Obesity and the associated inflammatory state in insulin-responsive tissues result in the release of pro-inflammatory cytokine that activates the stress-responsive MAPKs, p38 MAPK, and JNK. These MAPKs have figured prominently as critical effectors in physiological and pathophysiological hepatic inflammation.

Breast cancer is the most commonly diagnosed cancer in women in the United States. Breast cancer incidence rates, particularly among younger women, have been increasing since the 1930s, and are only partially explained by changes in parity, age at first birth, and improved screening and detection. Many questions remain unanswered regarding the mechanisms that underlie current risk.

Since December 2019, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) caused by 2019 Novel Coronavirus (2019-nCoV) has resulted in 89,000 cases of Corona Virus Disease 2019 (COVID-19), formerly known as Novel Coronavirus Pneumonia (NCP) in China, including 2,450 deaths.

Cardiac sarcomeres express a variant of troponin I (cTnI) that contains a unique N-terminal extension of ~30 amino acids with regulatory phosphorylation sites. The extension is important in the control of myofilament response to Ca²⁺, which contributes to the neuro-humoral regulation of the dynamics of cardiac contraction and relaxation.

Multiple types of discrete melanocytic choroidal lesions are currently recognized, including benign choroidal nevi, choroidal malignant melanomas, patches of choroidal melanocytosis, and foci of choroidal melanocytes stimulated paraneoplastically by a systemic nonmelanoma malignant neoplasm.

Recently, several studies and investigators have shown the beneficial effects of high dose dietary riboflavin (vitamin B2) in the treatment of keratoconus, post-refractive (LASIK, PRK & Radial Keratotomy) ectasia (with sunlight exposure) and patients treated with our own protocol (NIH Clinical Study – www.clinicaltrials.gov - # NCT 03095235) discovered significant relief for intractable migraine headaches and/or ophthalmic migraine (classic migraine visual symptoms without headache).

After one year in a pandemic, we mourn the loss of over half a million lives in the United States, and over four million worldwide, and remain concerned over the challenges facing the families of 35 million people in the United States, and 200 million worldwide, who have suffered from cases of COVID-19.

Levels of Intellectual Disability and Categories of Communicative Skills When conducting a patient interview, it is crucial to understand the individuals’ level of ID as well as their expressive language skills in order to communicate effectively

Loneliness is a distressing experience perceived as isolation and rejection. It has been recognized as a social problem throughout the existence of Homo sapiens, and is now considered, in conjunction with social isolation, to be an emergent public health problem affecting all age groups

Health intelligence on the frequency of cardiovascular disease (CVD) and its risk factors identifies targets and populations for preventative strategies and allows evaluation of health outcomes, behaviors and interventions in populations and health care settings.

In the realm of DNA repair, base excision repair (BER) protein, APE1/Ref-1 (Apurinic/Apyrimidinic Endonuclease 1/Redox Effector - 1, also called APE1) has been studied for decades. However, over the past decade, APE1 has been established as a key player in reduction-oxidation (redox) signaling. In the review by Caston et al. (The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease), multiple roles of APE1 in cancer and other diseases are summarized. 

MicroRNA (miRNAs) constitute a large family of highly conserved ~21-nucleotide-long small noncoding RNAs. In mammals it is calculated to control ~50% of proteincoding genes by regulation at the post-transcriptional level affecting mRNA degradation.

Traumatic brain injury (TBI) has a bimodal age distribution with peak incidence at age 24 and age 65 with worse outcomes developing in aged populations

Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies

Diabetes is a major healthcare concern worldwide. In addition to the financial burden estimated at $760 billion, the human suffering related to complications of diabetes as well as the disease itself are immense. Complications associated with diabetes affect both men and women, but there is a higher incidence reported in the aging population, women, and people of color.

Dementia and hypertension are highly prevalent, epidemiologically related chronic conditions disproportionately affecting older persons; approximately 97% of persons with dementia and 66% with hypertension are over the age of 65.

Multidrug resistant (MDR) bacteria, which are resistant to more than one antibiotic, present an enormous challenge for medical communities and organizations worldwide. For example, Acinetobacter baumannii is a highly contagious MDR gram-negative bacterium (GNB) that inhabits hospitals and causes 64% of urinary tract infections associated with the use of catheters. Alexopoulou et al. found that there were more healthcare-associated infections caused by GNB than Gram-positive Cocci (GPC) bacte

In 2019, approximately 38 million people were infected with HIV worldwide [1]. Although there is still no cure that successfully eradicates the disease, combination antiretroviral therapy (cART) has improved to a point where undetectable viral loads have become achievable and HIV carriers often live almost normal lives with very substantially increased average life expectancies compared to historical data.

In the process of rhegmatogenous retinal detachment (RRD), retinal homeostasis may be adversely affected with resultant modifications in retinal and choroidal tissue. Hypoxia and nutrient deprivation along with inflammation at the detached retina may lead to morphological and microvascularity alterations. These changes imply that the functional status of the macula may not be entirely restored despite anatomical repair.

APE1/Ref-1 (also called Ref-1) has been extensively studied for its role in DNA repair and reduction-oxidation (redox) signaling. The review titled: “The multifunctional APE1 DNA repair-redox signaling protein as a drug target in human disease” by Caston et. al. summarizes the molecular functions of Ref-1 and the role it plays in a number of diseases, with a specific focus on various types of cancer.

Extracellular matrix (ECM) surrounding cells in solid tissue provides mechanical support and communicates with cells through cell adhesion molecules (CAMs) at the cell surface. Integrin is a major group of CAMs represented by a family of αβ heterodimeric single transmembrane receptors. 

Exosomes are membranous vesicles ranging in size from 30–100 nm in diameter. They are secreted from multiple cell types into the body fluids through exocytosis, a process commonly used for receptor discharge and intercellular communications.

Chronic stress exposure is linked to health and performance deficits including mental disorders, chronic diseases, and metabolic conditions. Stress management is an active process of coping with internal or external stressors to prevent or dampen biological and psychological strain

Bladder cancer is one of the most common and expensive cancers in the United States, with an expected 81,400 new cases and 17,980 deaths in 2020 alone. The incidence is increased among white men and diagnoses often occur in the 7th decade of life.

MicroRNAs (miRNAs) are short double-stranded regulatory molecules derived from precursor transcripts called primary miRNAs (pri-miRNAs) and transcribing in the nucleus from chromosomal DNA by the RNA polymerase II. These pri-miRNAs were shown to contain internal imperfect hairpin structures which are processed by DCL (dicer-like) enzyme

Calcium (Ca²⁺) is an intracellular universal second messenger that regulates a variety of cellular processes. Many biological processes, including gene transcription, cell cycle, migration, and apoptosis, are affected by changes in intracellular Ca²⁺ signaling. Disruption of normal Ca²⁺ signaling can cause tumorigenic phenotypes.

Bone mineral content and density (BMC, BMD) losses, which may subsequently lead to osteopenia and osteoporosis, appear in various disuse (aging, space flight and its analogs, spinal cord injury, etc.) conditions. While diet and hormonal status impact BMC and BMD values, a major factor responsible for these losses are the

Flavopiridol (FVP; alvocidib), an FDA-approved orphan drug, has been studied in clinical trials under both single treatment and combination scenarios; several singleagent Phase I and Phase II clinical trials against leukemia, lymphomas, and solid tumors are active. To date, there have been more than 50 clinical trials involving FVP in the United States. Unfortunately, almost half of patients on FVP clinical trials showed serious adverse effects, implicating appropriate dosages need to be found and an alternative way to circumvent the toxicity of FVP with synergistic agents.

Upper extremity (UE) exoskeletons were developed for industrial applications where assistive force enhancement was needed, but there have also been developments for use in telemanipulation and virtual reality, clinical applications such as assistance in orthopedic surgery, and orthopedic rehabilitation. 

The etiology of fetal growth restriction is rooted in inadequate maternal-placental vascular malperfusion (MVM) of the placenta. Risk factors for MVM are broad and include maternal, fetal, and placental antecedent determinants.

Neuroinflammation is closely associated with various diseases including neuropathic pain. Microglia are immune cells in the central nervous system which are the main players of immunity and inflammation. Since microglia are activated by nerve injury, and they produce proinflammatory mediators to cause neuropathic pain, targeting activated microglia is considered to be a strategy for treating neuropathic pain.

New globally circulating SARS-CoV-2 strains are causing concern about evolution of virus transmissibility, fitness and immune evasion mechanisms. A variant emerging from the United Kingdom called SARS-CoV-2 VUI 202012/01, or B.1.1.7, is thought to exhibit increased transmissibility that results from replication 4-10 times faster than the original Wuhan virus (Wuhan-Hu-1). 

Since the declaration of COVID-19 as a pandemic in March 2020 [1], there have been more than 100 million reported cases of COVID-19 worldwide and more than 2.1 million deaths [2].

Meningiomas are common, primary brain tumors, accounting for up to 30% of intracranial neoplasms; they are usually slow-growing and benign [1]. Primary extra cranial meningiomas are rare, and approximately 2% of meningiomas are located extra cranially [2]. Furthermore, primary extra cranial meningiomas of the ear and temporal bone are exceedingly rare .

Among women living with HIV (WLWH), increases in body weight and body mass index (BMI, kg/m2) have been observed after switching to the antiretroviral therapies (ART) - Integrase Inhibitors (INSTI) and/or Tenofovir Alafenamide (TAF).

Cell Death has long been considered to be an inevitable part of the life cycle of a cell and hence, considered a familiar consequence of cellular life.

The present Commentary is a critical follow-up of a previous review about “Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases”, appeared in Clinical and Experimental Immunology last June 2019 [1].

The Wnt signaling is classified as two distinct pathways of canonical Wnt/β-catenin signaling, and the non-canonical pathways of planar cell polarity and Wnt/Ca²⁺ pathways. However, the scientific discoveries in recent years have shown that canonical and noncanonical Wnts pathways are intertwined and have complex interaction with other major signaling pathways such as hedgehog, Hippo and TOR signaling.

The outbreak of severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has led to coronavirus disease-19 (COVID-19); a pandemic disease that has resulted in devastating social, economic, morbidity and mortality burdens. SARS-CoV-2 infects cells following receptor-mediated endocytosis and priming by cellular proteases.

In 2019, approximately 56,770 new cases of pancreatic cancer were diagnosed in the United States, resulting in an estimated 45,750 deaths. Pancreatic cancer is one of the leading causes of cancer-related death, with a fiveyear survival rate of 9%. Based on the eighth edition of the American Joint Committee on Cancer (AJCC) staging system for pancreatic adenocarcinoma, multi-center analyses have validated that poorer prognosis is associated with node-positive disease (N1 and N2).

Macrophages are important cells of the innate immune system and play a crucial role in host immune defense against infection and injury [1-3]. Macrophages form the first line of defense against airborne particles and microbes through multiple functions including phagocytosis, production of cytokines and chemokines, and antigen presentation.

The COVID-19 pandemic has caused delivery of orthopaedic services to require extra consideration and substantial revision. Alternative ways to manage patients with urgent injuries have been instigated to minimize patient’s exposure to the disease, spread within the hospital system and reduce the overall impact on stretched resources.

The concept of immunotherapy has been traced as far back to third century BC Qin dynasty in China through the purposeful inoculation of Variola minor to prevent smallpox. 

Recent progress in the therapies used for patients with Non- Hodgkin’s lymphoma (NHL) has improved survival. In 2020, 77,240 people were diagnosed with NHL. Although it accounts for 4% of all cancers, the incidence has been reported to be decreasing in the last few years. About 26% of people will expire from NHL (15% males and 11% females).Non-Hodgkin lymphoma arises from the clonal expansion of B, T, and natural killer (NK) cells. There is a significant degree of heterogeneity in NHL and this is likely related to different degrees of differentiation and maturation of these cells. These hematological malignancies exhibit different tumor behavior and are responsive to different chemotherapy agents which impacts clinical outcomes. There are patients who can be cured with current regimens; however, subtypes such as indolent and some aggressive lymphomas remain incurable necessitating treatment with new therapies including immunotherapy, targeted therapy, CAR T cells, and hematopoietic stem cell transplant.

Until the early sixties, the concept prevailed that alcoholic liver disease (ALD), also termed alcohol-related liver disease (ARLD), results from malnutrition commonly observed among individuals consuming chronically high amounts of alcohol rather than being causally related to the use of alcoholic beverages. However, the malnutrition concept became a matter of debate because of the clinical observation that humans, even on a normal diet and without signs of underweight or malnutrition

Acute respiratory distress syndrome (ARDS) is the major cause of mortality among hospitalized acute lung injury (ALI) patients. Lung macrophages play an important role in maintaining the tissue-fluid homeostasis following injury. We recently showed that circulating monocytes recruited into the alveolar space suppressed the stimulator of type 1 interferon genes (STING) signaling in alveolar macrophages through sphingosine-1-phosphate (S1P). 

Chronic pain, defined as pain lasting longer than three months, is a significant public health burden and has been associated with depression, anxiety, poor quality of life and opioid use disorder (OUD).

A 59-year-old left hand dominant female was evaluated by a physical therapist. The patient had an 8-year history of chronic intermittent left elbow pain with a recent exacerbation occurring after moving furniture. Aggravating factors included holding a coffee cup, picking up trash bags, and lifting heavy dishes. Symptoms were eased by ice and Meloxicam as prescribed by her primary care provider.

The manufacture of scaffolds for wound healing has become important, especially the formation of tissuespecific scaffolding. In order to create scaffolds, it is essential to mimic the chemical composition, physical morphology and biological functions of the human body. Scaffolds can be created by using synthetic polymers (e.g. polycaprolactone) or natural polymers (e.g. chitosan) or a combination of both. The addition of natural polymers can be very advantageous as they can avoid

Since the discovery of the hepatitis B virus (HBV) by Blumberg et al., great progress has been made in understanding the pathogenesis of the virus and its role in hepatocellular carcinoma (HCC). It is estimated that hepatitis B is responsible for about 50% of the HCC cases worldwide. Because of geographic variations in HBV incidence, the burden of HBV-related HCC (HBV-HCC) is highest in endemic areas such as Asian-Pacific and sub- Saharan Africa and lowest in the United States and the West. The hepatitis B vaccines, developed in the 1980s, transformed the evolution of hepatitis B in the modern era. This was followed by high effective anti-viral that reduced HBV infections and HBV-HCC.

Gemcitabine is a synthetic pyrimidine nucleoside analogue which is administered intravenously as a chemotherapeutic to treat numerous cancers. Gemcitabine requires transport into cells and activation by phosphorylation, the resulting gemcitabine triphosphate is incorporated into newly synthesized DNA during cell division, inhibiting further DNA synthesis and causing cell death. Gemcitabine is used to treat cancers including those of the pancreas, lung, breast, colon, and ovary either as first or second line treatments as a single agent or in combination.

The neuropeptide Calcitonin Gene-Related Peptide (CGRP) is a 37-amino acid peptide, with a wide-range of biological activities including vasodilation, neurogenic inflammation, immune function and hypertension. In addition to these various roles, it has also been heavily implicated in metabolic disease, with roles in feeding, energy dissipation processes and pancreatic β-cell insulin secretion.

Deoxyribonucleic acid (DNA) methylation is a critical type of epigenetic modification that typically occurs in a specialized region of DNA, CpG-rich regions in the mammalian genome and is associated with regulating gene expression. Previous studies have revealed a strong association of change in DNA methylation with various diseases such as cancer, obesity and posttraumatic stress disorder (PTSD).

Forkhead transcription factors (TFs) often dimerize outside their extensive family, whereas bHLH transcription factors typically dimerize with E12/E47. Based on structural similarities, we predicted that a member of the former, Forkhead Box P1 (FOXP1), might heterodimerize with a member of the latter, MYOD1 (MyoD).

Epigenetic processes provide a mechanism for integrating metabolic inputs and translating them into various phenotypic outputs [1,2]. Indeed, epigenetic modifiers often require or are inhibited by key citric acid cycle (CAC) metabolites (e.g. succinate,

Due to use as human vaccines and therapies, the clostridial neurotoxins (CNTs) have been subjected to decades of scientific investigation using biophysical, electrophysiological, and pharmacological approaches to establish mechanisms of toxin action. 

At the end of 2019, a novel severe respiratory disease (coronavirus disease 2019, COVID-19) spread to Wuhan, China, it became pandemic in few months, with more than 41 million people infected worldwide as of October 2020. COVID-19 is caused by a novel virus called severe acute respiratory syndrome (SARS) CoV-2 to distinguish it from SARS-CoV that emerged in Guangdong province in China in 2003 and caused the severe clinical condition known as SARS. Like SARS-CoV, SARS- CoV-2 causes a severe inter

Ulnar neuropathy is the second most common peripheral neuropathy in the upper limb after carpal tunnel syndrome, with an incidence of 30 cases per 100,000 persons/year. It is characterized by the appearance of sensory symptoms such as pain, dysesthesia, and paresthesia, initially intermittent and then continuous, in the ulnar territory of the forearm and hand.

A 56-year-old Caucasian man was referred to an academic medical center for consideration of allogeneic hematopoietic stem cell transplantation (HSCT). One year earlier, he had seen his primary care physician for increased fatigue and decreased exercise tolerance, and a complete blood cell count showed a total white blood cell count of 2500/μL, hemoglobin of 7.2g/dL, and a platelet count of 110,000/μL. The white blood cell differential showed an absolute neutrophil count of 900/μL. The patient was referred to a hematologist who performed a bone marrow biopsy that showed a myelodysplastic syndrome with del(5q).

Hamstring injuries are the most common pathology reported in professional soccer players and represent about 10-30% of all injuries. The hamstring complex is comprised of three muscles located in the posterior compartment of the thigh including the semimembranosus (SM), semitendinosus (ST), and biceps femoris (BF), which is comprised of the long head (BFLH) and short head (BFSH).

Recently, Aras et al. reported that MNRR1, a nuclear DNA (nDNA)-encoded mitochondrial antigen, promotes cancer cell migration and the development of metastasis as a proof of concept supporting the participation of mitochondrial autoimmunity in breast carcinogenesis.

Idiopathic pulmonary fibrosis (IPF) is an irreversible fibrotic lung disease with unknown etiology [1-3]. Although two approved medications, pirfenidone and nintedanib, are able to slow down lung function decline in IPF patients, many other chronic pathologic conditions such as dyspnea and pulmonary hypertension (PH) and overall disease progression,

Cigarette smoke (CS) is a main risk factor for the development of various diseases, either via direct exposure of tissues to CS [1-3] or indirect exposure of remote organs to CS extracts (CSE) (Figure 1) [4-6]. The harmful impact is induced by exposure to the toxic CS substances, each cigarette contains approximately 7,000 chemicals. Out of

Chronic, non-healing, or slow to heal wounds present a significant and growing health problem in the United States, with an estimated 6.5 million people affected, at an annual cost of US $20 billion, with the highest risk groups represented by the elderly and the increasing prevalence of lifestyle diseases such as diabetes and obesity.

Cancer nanomedicine was originally developed for more efficient delivery of chemotherapeutic agents into tumor, and has been extensively employed as a therapeutic for cancer treatment owing to its unique features in drug delivery, diagnosis and imaging, as well as the therapeutic nature of some nanomaterials themselves.

Obesity has reached a global epidemic and it predisposes to the development of insulin resistance, type 2 diabetes and related metabolic diseases. Current interventions against obesity and/or type 2 diabetes such as calorie restriction, exercise, genetic manipulations or established pharmacological treatments have not been successful for many patients with obesity and/or type 2 diabetes.

Nausea and vomiting are protective defense mechanisms by which vomit competent species avoid ingestion of potentially toxic substances. More specifically, vomiting is the act of forceful expulsion of gastrointestinal contents through the mouth, whereas nausea is an unpleasant painless subjective feeling that one will imminently vomit.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) causes a mild respiratory infection in most individuals. However, a portion of patients develop a severe infection resulting in the need for mechanical ventilation and ultimately death. Currently, the median infection fatality rate of coronavirus disease 2019 (COVID-19) is estimated to be 0.27% .

Plastic is a composite material made from organic polymers and can be freely molded into a film, fiber, or plate by heat or pressure processing. In 1839, Goodyear proposed the vulcanization of natural rubbers, while E. Simon discovered polystyrene

At the end of 2019, a novel coronavirus was identified as the cause of a cluster of pneumonia cases in Wuhan, a city in the Hubei Province of China.

Probiotics are generally defined as nonpathogenic living organisms that have beneficial effects on host health. The term “probiotic” means “for life” that is derived from Greek language. At first, probiotics was defined as substances that are produced with microorganisms and promote the other microorganisms.

•  Clinicians need to understand the importance of clinical audit and take the necessary remedial actions to enhance their knowledge and skills to carry out clinical audit and improve the outcome.

• Clinicians also need to recognize the importance of follow-up and emphasize on it to improve the long-term

In this study, the safety and efficacy of liver biopsies performed by endoscopic ultrasound (EUS-LB) were compared with those performed via the traditional percutaneous route at our Medical Center between January 2018 and August 2019.

The use of molecular and genomic analysis of a cancer as a means to define a patient-specific treatment is interchangeably referred to as Precision Medicine, Personalized Medicine, or Genomically-directed medicine (herein, collectively PMED).

Tumors harboring mutations in certain oncogenes are often dependent on activation of certain pathways which becomes essential for the survival of the cancer cells. This condition is formally known as synthetic lethality, a state when simultaneous loss of two genes is lethal to a cancer cell, while the loss of the individual genes is not.

The failure to eradicate minimal residual disease often located at metastatic sites and/or the bone marrow niche continues to be a clinical barrier for successful treatments in cancer.

DNA microsatellites are tandemly repeating short (1-6 base pairs) DNA motifs, such as mononucleotide (A)n, dinucleotide (CA)n, trinucleotide (CAG)n, and tetranucleotide (AAAG)n, with each motif potentially repeating up to 50 times.

Fatty acid oxidation disorders unfortunately can result in the sudden unexplained death of infants. Mitochondrial trifunctional protein (MTP) deficiency is one such disease where long-chain fatty acids cannot be fully oxidized through beta-oxidation which, can lead to cardiac arrythmias in an infant.

Fluoropyrimidines have been extensively used for almost 6 decades to treat a variety of solid cancers, especially colon, gastric, anal, rectal, head & neck and breast. However, 31–34% of patients encountered grade 3–4 adverse events (AEs) with 0.5% mortality oftennecessitating dose reduction or discontinuation. 

In an early publication, we could show that striae distensae always develop perpendicular to the skin tension lines. In another article, we demonstrated that virtual skin tension lines are identical to the obvious Main Folding Lines; we recommended their use as optimal directions for orthopedic incisions, when inconspicuous scar formation is a prerequisite, as in children, younger adults, and women.

Magnesium is an essential mineral and cofactor for hundreds of enzymes and reactions. Magnesium is essential for the regulation of cell growth, division, and differentiation as well as protein synthesis, cell signaling and structural functions.

Being a sophisticated and highly organized living system, mammals harbor a large number of biomolecular machineries which represent a dynamic and complex network of interconnections responsible for the effective operation, development and survivability of their body cells. Sphingolipids are a special class of lipids in eukaryotic cells, which have recently gained the attention of researchers because of their involvement in several fundamental processes of living cells, including proliferation

Men who have sex with other men (MSM) comprise the single largest group of individuals contracting HIV in the United States, accounting for more than one-half of all new HIV diagnoses.

5-fluorouracil (5-FU), an antimetabolite in the fluoropyrimidine class, is the third most commonly used chemotherapeutic agent worldwide for the treatment of solid malignancies [1]. Despite advances in novel cancer therapies, commonly used in combination with fluoropyrimidines, 5-FU remains one of the most effective and safe chemotherapy agents to manage colorectal cancer (CRC).

Five months into the COVID-19 pandemic, the U.S. death toll from the virus has now surpassed 100,000 people. Many more cases remain nationwide, while an unknown number of patients currently harbor the virus asymptomatically. While health officials are now optimistic regarding the decline in prevalence and number of deaths due to COVID-19 and the possibility of a vaccine by the fall, we cannot lose sight of the bigger picture: the next pandemic.

In a recent paper, we introduced a variant of the classical Simeoni tumor growth model, and illustrated its value in assessing tumor growth in a reproducible mouse model for mammary tumors. Our modification consisted of incorporating delay differential equations in the mathematical formulation of the Simeoni model, to represent the delay in drug action often observed under chemotherapeutic or immunotherapeutic regimens.

Glucocorticoids (GCs) are defined by their role in maintaining glucose homeostasis and natural GCs are a class of corticosteroids secreted by the adrenal cortex. Cortisol is the most important natural GC in humans. Cellular cortisol levels are regulated by the tissue-specific metabolic enzymes 11β-hydroxysteroid dehydrogenase 1 and 2 (11β-HSD 1 and 2); 11β-HSD 1 converts inactive cortisone to active cortisol, while 11β-HSD 2 has the opposite function.

Observational studies have demonstrated association of metformin with reduced cancer incidence and mortality in multiple cancer types, including gastrointestinal (GI) malignancies. Anti-neoplastic effects of metformin are believed through many mechanisms including activation of AMP-activated protein kinase, which controls mammalian target of rapamycin (mTOR) growth regulatory pathway.

Charcot joint disease refers to the structural breakdown of the joints in the presence of neuropathy [1]. It has multiple pseudonyms but one of the most descriptive names of this condition is “Diabetic Neuroarthropathy.” The first cases studied by Jean-Marie Charcot however were not due to diabetic peripheral neuropathy but syphilis-related peripheral neuropathy.

While the global COVID-19 pandemic has challenged the entire humanity and health systems, it also triggered researchers to urgently perform clinical trials to assess the safety and efficacy of many agents and modalities to combat COVID-19. As of April 22, over 650 clinical studies have been registered both in USA and internationally. Results from these studies are also coming at a brisk pace in this unprecedented emergency.

Neurogenic lower urinary tract dysfunction (NLUTD) is highly prevalent in poststroke patients, leading to major impact on the quality of life (QoL) and healthcare resources. Pelvic floor muscle training (PFMT) has, over the past two decades, been recommended as first-line treatment for neurologically healthy patients with lower urinary tract symptoms (LUTS). 

Artificial Intelligence (AI) techniques represent a fascinating, provocative, and challenging discipline, are pervasive and of global importance. The European Commission summarized the current state in a White Paper on AI issues released on 19 February 2020, discussing various AI concepts that revolutionized many complex processes

Low back pain (LBP) is one of the most prevalent conditions that will affect 70-85% of individuals at some point in their life [1]. LBP accounts for 2.3% of all visits to the physician, and is the most common area of the body to experience pain [2]. Exercise has been a mainstay for managing persons with chronic low back pain for almost 40

In last decades, video-assisted thoracic surgery (VATS) together with robotic-assisted thoracic surgery (RATS) can be considered the biggest innovation in thoracic surgery. This approach drastically changed the way of performing surgical operations, improving patient’s outcome undergoing thoracic surgery.

Contraception encompasses the concept of avoiding a pregnancy, and is aimed at women of reproductive age who, although are sexually active, do not want to achieve any pregnancy at their option fertility preservation and family planning

Infectious diseases caused by microorganisms of the most varied natures and by viral entities cause millions of deaths every year. Around the world, viral infections have impacted civilizations’ circumstances since the earliest times, including the current panorama of the SARS-CoV-2 pandemic known as coronavirus disease in 2019 (COVID-19). In this sense, in the last century,

It is now well accepted that the ionizing radiation-generated reactive oxygen species (ROS), that constitute ~2/3 of the effects of external beam radiation, do not only produce direct tumor cell death, but also affect the surrounding microenvironment. Moreover, this indirect effect of radiation may result in systemic effects, specifically the initiation of an inflammatory response.

Diabetes is approaching epidemic proportions worldwide. In the United States, there are more than 30 million individuals having a confirmed diagnosis of diabetes [1,2]. Worldwide, the number of people with diabetes exceeds 400 million [3], and is expected to reach 550 million by 2030. Diabetes is associated with complications that affect nearly all systems, including vision.

Phosphoinositol 3 kinase (PI3K) defines a class of lipid kinases that have the ability to phosphorylate the inositol ring 3?-OH group in inositol phospholipids and therefore produce phosphatidylinositol (3,4,5)-trisphosphate (PIP3) [1]. PI3K encompasses a family of enzymes divided into: Class IA PI3K which includes three isomers (?, ?, ?) and Class IB which include the group (?).

With increasing rates of obesity, rates of type 2 diabetes and diabetic complications are expected to rise exponentially over the next few decades (American Diabetic Association). A key feature of type 2 diabetes is a resistance to insulin. Insulin signaling is key to a number of physiological processes, including glucose metabolism, cell growth, general gene expression, and apoptosis.

Different humanized mouse models have been introduced to enable HIV-1 research in vivo, which has been made possible by the development of immunodeficient mouse strains.

The insertion of dental implants immediately after teeth extractions has become a routine clinical procedure in implant dentistry. This treatment modality has received much attention and has shown favorable results [1-4]. Several studies have reported that successful osseointegration is possible when implants are inserted immediately

Autophagy was originally viewed as a widely conserved multistep lysosomal degradation pathway in eukaryotes. It includes the formation of autophagosomes, doublemembrane structures engulfing cytoplasm with damaged organelles during the degradation process.

The human induced pluripotent stem cell (iPSC) technology was developed more than ten years ago and has provided important tools for the mechanistic and cellular interrogation of many diseases [1]. To generate iPSC lines, somatic cells are reprogrammed into cells resembling embryonic stem cells by the overexpression of key transcription factors.

Worldwide, obesity is a public health concern and a metabolic ailment characterized by excessive adipose tissue accumulation resulting from an imbalance of energy expenditure and energy intake [1]. This disorder is a known risk factor for cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, hypertension, and metabolic

Type 2 diabetes (T2D) remains undiagnosed for many years in large number of persons living in developing countries. The cost of diagnostic tests and the invasive procedures involved in conventional screening methods remain a major setback to timely testing

The incidence of chronic diseases is rapidly increasing worldwide. It has been calculated that, in 2001, chronic diseases contributed to approximately 46% of the global burden of disease and 60% of the total reported deaths with that number expected to increase to 57% by 2020, when chronic diseases will account for almost 75% of all deaths worldwide.

HIV/AIDS continues to be a major public health disease accounting for 35 million deaths across the world. In 2016 alone, there were 1.8 million new HIV infections and 1 million deaths worldwide.

Inflammation can be caused by various environmental factors, including microbial infection and toxic chemical exposure. In response to inflammation, immune cells like macrophages, B and T lymphocytes, fibroblasts, endothelial cells, and various stromal cells secrete soluble polypeptide cytokine Tumor Necrosis Factor Alpha (TNF?)

Proton minibeam radiotherapy (pMBRT) is an external beam radiotherapy method with reduced side effects by taking advantage of spatial fractionation in the normal tissue. Due to scattering, the delivered small beams widen in the tissue ensuring a homogeneous dose distribution in the tumor. In this review, the physical and biological principles regarding dose distribution and healing effects are explained. In the last decade, several preclinical studies have been conducted addressing normal tissue sparing and tumor control in-vitro and in-vivo, using human skin tissue and mouse or rat models. The major results acquired in these studies are summarized. A further newly emerging therapy method is FLASH radiotherapy, i.e. the treatment using ultra-high dose rates. The possibility of combining these methods in proton minibeam FLASH therapy (pMB FLASH) is worked out. Additionally, technical feasibility and limitations will be discussed by looking at simulations as well as preclinical studies and also pointing out new ways of delivering the desired tumor dose, such as interlacing. We will also highlight the opportunities that emerge regarding high dose radiation, hypofractionation and the combination with immunotherapy.

Although NK cells are recognized as effector lymphocytes of the innate immune system, they also regulate the adaptive immune response by releasing inflammatory cytokines and developing immunological memory. Unlike other lymphocytes such as T or B cells, NK cells do not express rearrangeable, antigen-specific receptors. 

Cancer has its own disease burden and patients usually suffer from symptom clusters when they are referred for palliative treatment. Identification of symptom cluster trajectories will help clinician to take into account measures that can optimize quality of life of palliative patients. Therefore the aim of this paper is to determine the overall prevalence of symptoms and symptoms clusters in different disease groups according to etiology at the time of first visit to Palliative care clinic by using HIS Palliative First Assessment note indicating Edmonton symptom scale.

Diabetes mellitus (DM) is an age-related metabolic disorder affecting 347 million people in modern society. Expanding its prevalence beyond developed countries, DM has emerged as a global public health issue associated with a high morbidity and mortality.

Addiction is defined as being a primary chronic disease of the brain reward, motivation, and memory in this complex circuitry. A dysfunction in this complex circuitry can lead to certain manifestations in an individual [1]. The individual who suffers from addiction does not have the ability to abstain from this harmful pursuit and, as a result,

Cellular components are attractive targets for antiviral therapy because they do not mutate as readily as do viral proteins do [1-3]. The identification of CCR₅ as an HIV-1 coreceptor [4-7], facilitated by the discovery of the antiviral activities of CCR₅ ligand ?-chemokines [8], resulted in the development of new viral entry inhibitors to block CCR₅ binding, including both- small molecules and CCR₅ antibodies

A national perinatal survey in France in 2016 showed that 12.2% of women have instrumentally assisted vaginal births with vacuum extraction used in 49.8% of cases, making it the most frequently used form of obstetrical assistance.

Human embryogenesis and the development of its most unique product, the human brain, are believed to be precisely regulated by factors adopted during human
evolution that differentiate us from other species.

Alzheimer disease (AD) is a debilitating neurodegenerative disorder characterized by extracellular deposition of the amyloid β-protein (Aβ) and intraneuronal accumulation of the microtubule-associated protein, tau

Anorexia nervosa (AN) is an eating disorder characterized by a fear of gaining weight and self-starvation, leading to life-threatening weight loss [1]. It occurs predominately in women and frequently begins during adolescence.

Uromodulin (UMOD) is a glycoprotein expressed by the epithelial cells of the thick ascending limb of Henle’s loop in the kidney. Research has shown that increased uromodulin expression may be associated with lower risk of cardiovascular disease in adults.

Dravet syndrome (DS) is an intractable childhood epilepsy disorder affecting one in 15,000 to 20,000 births [1]. It is caused by de novo heterozygous lossof- function mutations in the SCN1A gene encoding the brain type-I voltage-gated sodium channel Na_v1.1