Detection of Undiagnosed Elevated Cardiovascular Risk Biomarkers among HIV-Positive Patients on Antiretroviral Therapy (ART) in Kigali-City, Rwanda
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.
Comparison of Horizontal blaCTX-M Gene Transfer via Conjugation among Extended Spectrum β-Lactamases Producing Escherichia coli Isolates from Patients with Urinary Tract Infection, Their Animals and Environment
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 blaCTX-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.
Uhthoff ’s Phenomenon as Presentation of COVID-19 Infection
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.
Suicide and Violent Behavior in Psychotic Inpatients
This study compares the association between psychosis, suicide, and violent behavior in patients admitted and discharged from the psychiatric ward. Methods: This study used a cross-sectional design. The experimental study was done with all the psychotic patients fulfilling the inclusion criteria upon admission and discharge from a teaching hospital in Malaysia. The study was conducted for a duration of five months from March to July 2022.
Preliminary Evidence of Differentially Induced Immune Responses by Microparticle-adsorbed LPS in Patients with Crohn’s Disease
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.
Redox Homeostasis in Well-differentiated Primary Human Nasal Epithelial Cells
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.
Resveratrol and Astaxanthin Protect Primary Human Nasal Epithelial Cells Cultured at an Air-liquid Interface from an Acute Oxidant Exposure
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.
Surgical Fixation of Severe Rib Fractures: A Systematic Literature Review and Meta-Analysis
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.
Going above and Beyond: Using an Attenuated Herpes Viral Vaccine Vector to Elicit Protective Immune Responses Through Neutralizing and Non-neutralizing Functions of Antibodies
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 Duration of Mechanical Ventilation is the Main Cause of Bacterial/Fungal Superinfection in Critically Ill Patients with COVID-19 at Altitude
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).
The Issue of Monocyte Activation in ASD: Troubles with Translation
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.
The Future of Jail-Based Competency Treatment: Commentary from 30,000 Feet
In their recent article, “Jail-Based Competency Treatment Comes of Age,” Jennings et al.  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.
Clutch Control: Changing the Speed and Direction of CAR-T Cell Therapy
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.
Military Training: Does It predispose service personnel to Negative Mental Health Issues?
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.
Concomitant Langerhans Cell Histiocytosis and Chronic Myelomonocytic Leukaemia Responding to 5-azacitidine
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.
Expression and Regulation of FNDC5/irisin in Periodontium and Dental Pulp
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.
Sex Differences in Diabetic Ocular Surface Complications and Dysregulation of the OGF-OGFr Pathway
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 Induced Hypopigmentation and Neutropenia in a Patient with Gastric Gastrointestinal Stromal Tumor
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 Essential Elements of the PNF-concept, an Educational Narrative
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.
The Impact of Fluid Resuscitation Timeliness in Geriatric Patients with Sepsis: A Single Center Retrospective Cohort Study
Sepsis is a key driver of worldwide mortality, representing close to 20% of global deaths in 2017 . Approximately half of patients hospitalized with sepsis are 65 years and older . 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 with Neutrophilia: Two Etiologic Pathways for a Rare Presentation of a Common Diagnosis
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.
Beta 3-Adrenergic Receptor (β3-AR) Activation at the End of Sustained Ischemia and/or Early Reperfusion may Prove to be a Valuable Cardioprotective Strategy
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.
Estimated Plasma Volume Status (ePVS) for Diastolic Heart Failure in the Intensive Care Unit: A Retrospective Cohort Study
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.
Pharmacologic Therapies for Non-Muscle Invasive Bladder Cancer: Current and Future Treatments
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.
Review of Renal Transplantation of Hepatitis C Viremic Donor Organs into Aviremic Recipients
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.
Evolving Policies and Practices for Organ Recovery and Non- Lung Organ Transplantation in Candidates Recovering from COVID-2019 - A Review
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-
COVID-19 Delays Presentation and Management of Acute Coronary Syndrome
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.
Relative COVID-19 Vaccine Booster Effectiveness and ClinicalEpidemiological Characteristics Before and After 29 Days of Shot
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.
Gender Disparities in Outcomes Following Pulmonary Embolism Treatment in the Intensive Care Unit; A Multi-center Retrospective Cohort Study
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 . PE remains one of the leading causes of poor prognosis and death, particularly when a shock or right ventricular failure occurs . According to studies, PE is generally manifested in a nonspecific manner
Pregnancy Outcomes in Pregnant Women with HIV on Tenofovir Disoproxil Fumarate (TDF) Compared to Tenofovir Alafenamide (TAF)
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.
Impact of Sleep on Autophagy and Neurodegenerative Disease: Sleeping Your Mind Clear
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).
SARS-CoV-2 Mutations, Diagnosis and Their Concern
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.
Inulin Supplementation Mitigates Gut Dysbiosis and Brain Impairment Induced by Mild Traumatic Brain Injury during Chronic Phase
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.
Emerging Potential of Plant Virus Nanoparticles (PVNPs) in Anticancer Immunotherapies
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.
Commentary on NOBOX Mutations in Premature Ovarian Insufficiency
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.
Peritoneal Imaging may be the Last Piece of the Puzzle for Precision Evaluation of Peritoneal Function
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 . 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.
Escherichia coli Stress, Multi-cellularity, and the Generation of the Quorum Sensing Peptide EDF
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.
Karyotypic Profile of Chronic Myeloid Leukemia in Patients Diagnosed at Tertiary Level in Afghanistan
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.
c-JUN n-Terminal Kinase (JNK) Signaling in Autosomal Dominant Polycystic Kidney Disease
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).
Glucose Metabolism is a Better Marker for Predicting Clinical Alzheimer’s Disease than Amyloid or Tau
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 .
A New Adaptive Procedure for Estimating Perceptual Thresholds: The Effects of Observer Bias and Its Correction
Perceptual thresholds might vary due to different variables such as fatigue, fluctuations of attention, or sensory learning . Adaptive threshold estimation procedures are most effective by providing quasi-instantaneous estimates of an otherwise fluctuating sensory threshold.
The RiVUR Study Outcomes and Implications on the Management of Vesicoureteral Reflux
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.
The Outcome of Tumor Ablation Therapies is Determined by Stress Signaling Networks
Increasingly prominent roles in interventional oncology are held by various tumor ablation therapies performed by direct applications of local acute trauma-inducing insult to the targeted lesion aiming for its rapid in situ destruction. These therapies include treatments based on various forms of thermal energy delivery (photothermal, cryoablation, microwave ablation, radiofrequency ablation), non-thermal illumination (photodynamic therapy), electric field exposure, or high hydrostatic pressure
First In silico Structural Model of Glucokinase-1 from Phytophthora infestans Reveals a Possible Pyrophosphate Binding Site
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 Use of Consumer Wearable Physical Activity Monitors in Clinical Populations with Functional L imitations
The prevalence of many musculoskeletal and cardiovascular diseases that cause limitations in physical functioning has increased globally  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
Humanized Chimeric Antigen Receptor (CAR) T 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).
A Protocol for the Generation of Treatment-naïve Biopsy-derived Diffuse Intrinsic Pontine Glioma and Diffuse Midline Glioma Models
Diffuse intrinsic pontine glioma (DIPG) is an aggressive brain tumor that arises in the ventral pons during middle childhood.
The Loneliness, Loss and Reflections Set off by COVID-19
“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”
Capillary Stalling: A Mechanism of Decreased Cerebral Blood Flow in AD/ADRD
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.
Do Support Vector Machines Play a Role in Stratifying Patient Population Based on Cancer Biomarkers
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
Exploring and Targeting the Tumor Immune Microenvironment of Neuroblastoma
Neuroblastoma is derived from the developing sympathetic nervous system and is the most common extracranial solid tumor of childhood.
ProLung™-budesonide Inhibits SARS-CoV-2 Replication and Reduces Lung Inflammation
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.
Plasminogen Activator Inhibitor-1 and Oncogenesis in the Liver Disease
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.
Commentary on: Peptidylglycine alpha-amidating Monooxygenase is Required for Atrial Secretory Granule Formation
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.
Targeting Cullin-RING E3 Ubiquitin Ligase 4 by Small Molecule Modulators
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.
Cortical Visual Impairment (CVI): An Atypical Manifestation of Osmotic Demyelination Syndrome in a Child
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 . ODS has been described most frequently in association with a rapid correction of hyponatremia, though it may occur with other electrolyte or metabolic abnormalities.
Strong Association Between Placental Pathology and Second-trimester Miscarriage
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 . After six weeks, survival rates improve rapidly as 90% of the remainder will survive to term.
Polycyclic Aromatic Hydrocarbons and Mammary Cancer Risk: Does Obesity Matter too?
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.
How to Prevent Rehospitalization in Patients with COVID-19
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.
NH2-Terminal Cleavage of Cardiac Troponin I Signals Adaptive Response to Cardiac Stressors
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.
Focal Aggregates of Normal or Near Normal Uveal Melanocytes (FANNUMs) in the Choroid. A Practical Clinical Category of Small Ophthalmoscopically Evident Discrete Melanocytic Choroidal Lesions
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.
Mega-Dose Dietary Riboflavin in Treatment in Keratoconus, Post-Refractive Cornea Ectasia and Migraine. Has Its Time Arrived?
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).
Preparing for a More Public Health-Aware Practice of Medicine in Response to COVID-19
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.
Interviewing Techniques for Patients with Intellectual Disability
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
“All the lonely people, where do they all belong?”
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
Prevalence of Cardiovascular Risk Factors in Osteoarthritis Patients Derived from Primary Care Records: A Systematic Review of Observational Studies
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.
APE1/Ref-1 – One Target with Multiple Indications: Emerging Aspects and New Directions
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.
The Importance of miRNA Identification During Respiratory Viral Infections
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.
Differential Fecal Microbiome Dysbiosis after Equivalent Traumatic Brain Injury in Aged Versus Young Adult Mice
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
The Spread of Spectrin in Ataxia and Neurodegenerative Disease
Experimental and hereditary defects in the ubiquitous scaffolding proteins of the spectrin gene family cause an array of neuropathologies
Dysregulation of the OGF-OGFr Pathway and Associated Diabetic Complications
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.
Blood Pressure Lowering May Decrease Cognitive Decline; But Are We Ready to Lower Blood Pressure in the Real World?
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.
Antisense Inhibition of accA in E. coli Suppressed luxS Expression and Increased Antibiotic Susceptibility
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
Toward Personalized Medicine for HIV/AIDS
In 2019, approximately 38 million people were infected with HIV worldwide . 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.
Macular Microcirculation after Rhegmatogenous Retinal Detachment Repair Evaluated by OCT-Angiography
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.
Phosphorylation of RIAM Activates Its Adaptor Function in Mediating Integrin Signaling
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.
Exosome to Promote Cancer Progression via Its Bioactive Cargoes
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.
Measuring the Impact of Stressors through Self-reporting on the Temporal Nature of How Perceived Stress Emerges and Dissipates
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
Immune Checkpoint Inhibitors in the Management of Urothelial Carcinoma
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.
Possible Functions of the Conserved Peptides Encoded by the RNA - precursors of miRNAs in Plants
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
Ca2 /calmodulin-dependent Protein Kinases in Leukemia Development
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.
Exercise, Strains and Their Impact on Bone Mineral Content and Density Losses
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
Performance Validation of An Upper Limb Exoskeleton Using Joint ROM Signal
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.
Early Onset Fetal Growth Restriction: Does Path to Diagnosis Impact Outcomes and Pathology?
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.
Effects of a CB2 Subtype Selective Agonist ABK5-1 on Cytokine Production in Microglia
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.
Structural Consequences of Variation in SARS-CoV-2 B.1.1.7
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).
COVID-19 Disease and SARS-CoV-2 Vaccination in Patients with Cancer
Since the declaration of COVID-19 as a pandemic in March 2020 , there have been more than 100 million reported cases of COVID-19 worldwide and more than 2.1 million deaths .
Primary Temporal Bone Meningioma Presenting as Chronic Mastoiditis and Sigmoid Sinus Thrombosis: Report of a Case with Literature Analysis
Meningiomas are common, primary brain tumors, accounting for up to 30% of intracranial neoplasms; they are usually slow-growing and benign . Primary extra cranial meningiomas are rare, and approximately 2% of meningiomas are located extra cranially . Furthermore, primary extra cranial meningiomas of the ear and temporal bone are exceedingly rare .
Commentary on Lahiri et al. Weight and Body Mass Index Change After Switching to Integrase Inhibitors or Tenofovir Alafenamide Among Women Living with HIV
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).
Immunogenic Cell Death: A Step Ahead of Autophagy in Cancer Therapy
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.
News About the Extracellular Vesicles from Mesenchymal Stem Cells: Functions, Therapy and Protection from COVID-19
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 .
Wnt Signaling Cascades and Their Role in Coronary Artery Health and Disease
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.
Possible Therapeutic Use of Natural Compounds Against COVID-19
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.
M1 Macrophages are More Susceptible to Necroptosis
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.
Efficacy of a Virtual Fracture Clinic Model Created During Covid-19 Pandemic
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.
High Expression of TIM 3 and Galectin 9 on Immunohistochemistry Staining of Tumor Specimen at Diagnosis in Pediatric Patients with Ewing Sarcoma
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.
Alcoholic Liver Disease and the co-triggering Role of MEOS with Its CYP 2E1 Catalytic Cycle and ROS
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
S1P Generation by Sphingosine Kinase-2 in Recruited Macrophages Resolves Lung Inflammation by Blocking STING Signaling in Alveolar Macrophages
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).
From Silos to Solidarity: Case Study of a Patient-Centered, Integrative Approach to Opioid Tapering and Chronic Pain Mitigation in a Multidisciplinary AIDS Clinic
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).
Avulsion of the Common Extensor Tendon and Radial Collateral Ligament Tear
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.
Nanofibers Based on Concentrated Collagen Hydrolysate Loaded with Essential Oils
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
Are We Close to Achieving a HBV Cure? Risk for Hepatocellular Carcinoma Persists Despite Long-term HBV Suppression: An Update on Our Experience
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 in the Era of Cancer Immunotherapy
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.
Can Monoclonal Antibodies against CGRP Offer New Treatment Options for Type 2 Diabetes?
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.
RANDOMIZE: A Web Server for Data Randomization
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).
FOXP1 Interacts with MyoD to Repress its Transcription and Myoblast Conversion
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).
Succinate Accumulation Links Mitochondrial MnSOD Depletion to Aberrant Nuclear DNA Methylation and Altered Cell Fate
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,
Resolving the Molecular Steps in Clostridial Neurotoxin Light Chain Translocation
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.
Rapid Inactivation of SARS-CoV-2 by Coupling Tungsten Trioxide (WO3) Photocatalyst with Copper Nanoclusters
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
Submuscular Anterior Transposition for Treatment of Ulnar Nerve Syndrome: Outcomes and Final Satisfaction
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.
When Should Transplant Physicians Think about Familial Blood Cancers?
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).
Hamstrings Injuries with MRI Findings in a Major League Soccer Team
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).
Mitochondria Autoimmunity and MNRR1 in Breast Carcinogenesis: A Review
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.
Identification of the Molecular Basis of Anti-fibrotic Effects of Soluble Guanylate Cyclase Activator Using the Human Lung Fibroblast
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,
The Involvement of 18 kDa Translocator Protein (TSPO) in Cigarette Smoke-related Diseases: A Review
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
Improved Wound Closure Rates and Mechanical Properties Resembling Native Skin in Murine Diabetic Wounds Treated with a Tropoelastin and Collagen Wound Healing Device
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: Strategies to Enhance Tumor Delivery and Immunotherapy
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.
Improving Obesity and Insulin Resistance by Targeting Skeletal Muscle MKP-1
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.
Role of PI3K/Akt/GSK-3 Pathway in Emesis and Potential New Antiemetics
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.
Potentials of Interferons and Hydroxychloroquine for the Prophylaxis and Early Treatment of COVID-19
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% .
Developing Neo-bioplastics for the Realization of Carbon Sustainable Society
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
Early Insights into COVID-19 in Persons Living with HIV and Cardiovascular Manifestations
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.
Application of Encapsulated Probiotics in Health Care
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.
A Clinical Audit on the Follow-up Rate and Endodontic Outcome of Root Canal Therapy Performed by Dental Undergraduates
• 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
Endoscopic Ultrasound-Guided Liver Biopsy; the Pathologist’s Perspective
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 Challenge of Cognitive Dissonance in the Delivery of Precision Medicine in Veterinary Oncology
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).
Synthetic Lethal Drug Combinations Targeting Proteasome and Histone Deacetylase Inhibitors in TP53-Mutated Cancers
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 Role of ERO1α in Modulating Cancer Progression and Immune Escape
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.
Immunological Features with DNA Microsatellite Alterations in Patients with Colorectal 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.
Pharmacogenetic Variants in the DPYD and TYMS Genes are Clinically Significant Predictors of Fluoropyrimidine Toxicity: Are We Ready for Use in our Clinical Practice
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.
Clinical and Histological Proof that Surgical Incisions along Skin Folding Lines Result in Optimal Scars
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.
Hypomagnesemia and Outcomes in Hematologic Malignancies
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.
Role of Sphingolipid Signaling in Glomerular Diseases: Focus on DKD and FSGS
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
Older Versus Younger Men Who Have Sex with Men: Awareness of and Potential Barriers to the Use of Pre-Exposure Prophylaxis (PrEP) Medication to Prevent the Transmission of HIV
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.
Safety and Efficacy of s-MOX Regimen in Patients with Colorectal Cancer Who Developed Cardiotoxicity Following Fluoropyrimidine Administration: A Case Series
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 . 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).
Lessons Learnt from COVID-19: How Can We Prepare for Another Pandemic?
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.
Impact of Cisplatin Dosing Regimens on Mammary Tumor Growth in an Animal Model
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.
The Effect of Glucocorticoids on Angiogenesis in the Treatment of Solid Tumors
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.
Prospective Evaluation of Effect of Metformin on Activation of AMP-activated Protein Kinase (AMPK) and Disease Control in a Sub-group Analysis of Patients with GI Malignancies
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.
Rearfoot and Ankle Reconstruction for Charcot Joint Disease: A Review
Charcot joint disease refers to the structural breakdown of the joints in the presence of neuropathy . 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.
No Studies in Stroke Regarding Brain fMRI Activity and Pelvic Floor Muscle Training/Activation - Only Studies in Non-stroke Population: A Review of Neuroimaging Studies
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).
DILI, HILI, RUCAM Algorithm, and AI, the Artificial Intelligence: Provocative issues, Progress, and Proposals
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
Pain Outcomes with an Elliptical Regimen (POWER) Study: Identifying the Proper Dosage of Exercise for Therapeutic Effect in Persons with Chronic Back Pain
Low back pain (LBP) is one of the most prevalent conditions that will affect 70-85% of individuals at some point in their life . LBP accounts for 2.3% of all visits to the physician, and is the most common area of the body to experience pain . Exercise has been a mainstay for managing persons with chronic low back pain for almost 40
Uniportal VATS Lobectomy for Lung Cancer: Feasibility and Cost Effectiveness in a Single Center Experience
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.
Family Planning Laboratory Review of Factors Affecting the Choice of Contraceptive Methods in Three Teenagers' Populations in Thrace, Greece
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
Exploiting Nanotechnology to Target Viruses
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,
Emerging Role of TRPML1 Mucolipin Endolysosomal Channel in Cancer
The transient receptor potential mucolipin 1 (TRPML1) is an endolysosomal channel belonging to the TRP family. Clinically, mutations of TRPML1 have been responsible for a severe lysosomal storage disorder called mucolipidosis type IV.
Manipulating Oxidative Stress Following Ionizing Radiation
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.
Naltrexone as a Novel Therapeutic for Diabetic Corneal Complications
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 , and is expected to reach 550 million by 2030. Diabetes is associated with complications that affect nearly all systems, including vision.
Targeting the PI3K/AKT/mTOR/NFkB Axis in Ovarian Cancer
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) . PI3K encompasses a family of enzymes divided into: Class IA PI3K which includes three isomers (?, ?, ?) and Class IB which include the group (?).
Insulin Signal Transduction is Impaired in the Type 2 Diabetic Retina
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.
Use of Humanized Mouse Models for Studying HIV-1 Infection, Pathogenesis and Persistence
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.
Does the Immediate Dental Implant Placement into Fresh Extraction Sockets Decrease the Marginal Bone Lose?
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: When to strike?
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.
Mechanistic and Translational Advances Using iPSC-Derived Blood Cells
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 . To generate iPSC lines, somatic cells are reprogrammed into cells resembling embryonic stem cells by the overexpression of key transcription factors.
Flow Cytometric Characterization of Accidental Cell Death Highlights Connections to Regulated Cell Death
Damage-Associated Molecular Patterns (DAMPs) are known by their nature to cause inflammatory responses in numerous disease states from cancer, trauma to age related diseases (e.g. atherosclerosis, Alzheimer’s and Parkinson’s diseases), these molecules are released by cells undergoing cell death.
Energy Expenditure and Nutrition in Neurogenic Obesity following Spinal Cord Injury
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 . This disorder is a known risk factor for cardiovascular disease, type 2 diabetes mellitus, dyslipidemia, hypertension, and metabolic
Cut-off Value of Random Blood Glucose among Asian Indians for Preliminary Screening of Persons with Prediabetes and Undetected Type 2 Diabetes Defined by the Glycosylated Haemoglobin Criteria
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 Global Rise of Chronic Diseases: Why Broaden the Paradigm to Include Tick-borne Illness and Environmental Toxin Exposure?
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.
Health Workers’ Perspectives on the Outcomes, Enablers, and Barriers to the Implementation of HIV “Test and Treat” Guidelines in Abuja, Nigeria
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.
TNFAIP8: Inflammation, Immunity and Human Diseases
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?)
pMB FLASH - Status and Perspectives of Combining Proton Minibeam with FLASH Radiotherapy
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.
Chimeric Antigen Receptor CAR NK Cells Emerging Immunotherapy for the Treatment of Cancer
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.
Prevalence of Symptom Clusters in Cancer Patients at First Presentation in Palliative Care Clinic as per Different Disease Groups
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.
The Profiling and Role of miRNAs in Diabetes Mellitus
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.
The Health Effects of the Abuse of Ketamine
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 . The individual who suffers from addiction does not have the ability to abstain from this harmful pursuit and, as a result,
CCR5 Inhibitors and HIV-1 Infection
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 , resulted in the development of new viral entry inhibitors to block CCR5 binding, including both- small molecules and CCR5 antibodies
Preliminary Study Assessing the Efficiency of a New Singleuse Obstetrical Vacuum Device: Icup2®
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.
Retroviral Elements in Human Evolution and Neural Development
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.
Cathepsin D: A Candidate Link between Amyloid β-protein and Tauopathy in Alzheimer Disease
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
Commentary on Vulnerability and Resilience to Activity- Based Anorexia and the Role of Dopamine
Anorexia nervosa (AN) is an eating disorder characterized by a fear of gaining weight and self-starvation, leading to life-threatening weight loss . It occurs predominately in women and frequently begins during adolescence.
Commentary: Use of BACTRAC Proteomic Database-Uromodulin Protein Expression During Ischemic Stroke
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.
Combined Antiseizure Efficacy of Cannabidiol and Clonazepam in a Conditional Mouse Model of Dravet Syndrome
Dravet syndrome (DS) is an intractable childhood epilepsy disorder affecting one in 15,000 to 20,000 births . It is caused by de novo heterozygous lossof- function mutations in the SCN1A gene encoding the brain type-I voltage-gated sodium channel Nav1.1
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