The Striking Power of Amniotic Fluid and Its Exosomes Collected at the End of a Normal Pregnancy on Severe Inflammation and Tissue Repair.

With this short communication, which contains a new case report on diabetic ulcer, we summarize our research progress in treating several complex conditions at a point where currently available treatments were failing to help the affected patients. We review the first case of lower back pain due to severe spondylitis (T12-L1) treated with intravenous injections of a sterile fraction of human purified amniotic fluid (ViX001) obtained from thoroughly screened volunteers at the time of planned c-section at the term of normal pregnancies. Then, we review the first case of recalcitrant diabetic ulcer treated successfully by twice-daily applications of ViX001 directly on the wound and describe another case of diabetic ulcer treated successfully with ViX001.

Treating amyotrophic lateral sclerosis with allogeneic Schwann cell-derived exosomal vesicles: a case report.

Schwann cells are essential for the maintenance and function of motor neurons, axonal networks, and the neuromuscular junction. In amyotrophic lateral sclerosis, where motor neuron function is progressively lost, Schwann cell function may also be impaired. Recently, important signaling and potential trophic activities of Schwann cell-derived exosomal vesicles have been reported.

First Case of Severe Pain and Inflammation Reduction by Application of Purified Amniotic Fluid on Active Lesions of a Patient with Pyoderma Gangrenosum.

We report the first case of severe pain and inflammation reduction by application of purified amniotic fluid on active lesions of a patient with pyoderma gangrenosum. We describe the impact of every third-day skin applications of a sterile fraction (4ml) from human purified amniotic fluid (ViX001) obtained from thoroughly screened volunteers at the time of planned c-section at the term of normal pregnancies. The product ViX001 was generated through a proprietary process and kept in frozen one or two milliliters cryovials (protein content was ~1mg/ml) and thawed just prior to applications.

First Case of Debilitating Lower Back Pain Induced by Severe Inflammation of Lumbar Joints, Healed by Intravenous Infusions of Purified Amniotic Fluid.

We report the first case of debilitating lower back pain induced by spondylitis with end plate inflammation of the lumbar spine, treated successfully by bi-weekly intravenous injections of a sterile fraction (1ml) from human purified amniotic fluid (ViX001) obtained from thoroughly screened volunteers at the time of planned c-section at the term of normal pregnancies. Our product ViX001 was generated through a proprietary process and kept in frozen one milliliter (1 ml) cryvials (protein content was ~1mg/ml) and thawed just prior to injections. Pain improvement was recorded weekly, and inflammation suppression was confirmed by monthly MRIs of the lumbar spine.

First Case of Accelerated Healing of a Recalcitrant Diabetic Ulcer Using Purified Amniotic Fluid.

We report the first case of recalcitrant diabetic wound treated successfully by twice-daily applications of a sterile fraction of human purified amniotic fluid (ViX001) obtained from thoroughly screened volunteers at the time of planned c-section at the term of normal pregnancies. Our product ViX001 was generated through a proprietary process and kept in frozen one milliliter (1 ml) vials (protein content was ~1mg/ml) thawed prior to applications (shelf life at 34oF of at least two weeks).

Rivalry between Humans and Coronaviruses: Unanticipated Impact of Omicron.

With our prior Commentary we discussed the rivalry between ideation (humans) and mutations (viruses), (https://www.ncbi.nlm.

Pregnancy, a unique case of heterochronic parabiosis and peripartum cardiomyopathy.

: A loss of endogenous stem cells capable of tissue repair and regeneration drives the biological process that we recognize as "aging". Recovery of stem cell-mediated repair and regenerative functions in aged animals has been reported in murine heterochronic parabiosis experiments. : Herein we will review how pregnancy is an unusual form of heterochronic parabiosis, as the placenta prevents the exchange of most blood cells between parabionts.

Rivalry between human ideation and virus mutation: two competing means of sustainability.

For the first time in human history, obtaining a COVID-19 vaccine has become essential for the sustainability of our species. As an amazing product of collective ideation, remarkably safe and efficient vaccines have been invented, tested, distributed, and administered to the population on a voluntary basis. The fast-mutating individual behavior of the virus is probably guided by a similar goal of the sustainability of the species.

Evaluation of exosome derivatives as bio-informational reprogramming therapy for cancer.

Exosomes are nanoparticle sized (100 ± 50 nm) extracellular vesicles (ECVs) that play important roles in cell-to-cell communication. They do this by utilizing their natural ability to shuttle signaling molecules across the cellular microenvironment and promote paracrine signaling. Currently, exosomes are being explored for their potential as therapeutic agents for various degenerative diseases including cancer.

COVID-19 real-world data for the US and lessons to reopen business.

This Pearl article recounts the story of a US corporation, Lennar, the nation's leading homebuilder, an essential function in the US (not allowed to lock down), when faced with the coronavirus disease 2019 (COVID-19) pandemic at the end of February 2020. The culture of the company, which allowed it to proceed safely, is one of cohesion, trust, teamwork, and respect for fellow humans. Theirs is a culture in which the safety, wellness, and health of the associates (employees) and the communities they serve is the number one priority.

PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment.

Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that pro-angiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis.

Time for Well-Powered Controlled Prospective Studies to Test a Causal Role for Herpes Viruses in Alzheimer's Disease Using Antiherpetic Drugs.

Twenty-six phase III studies on Alzheimer's disease are ongoing or have been completed in 2018. Most of these studies are targeting amyloid-beta, its production, polymerization, and/or multiple interactions. None of the amyloid-beta studies seem to affect positively the clinical outcome of patients with Alzheimer's disease thus far, no matter the advancement of disease.

Virus Cooperation, ZIKV Viremia and in Utero Fetus Infection.

With growth and exponential globe trotter traveling of the human population, and many more conducive factors, the likelihood of merging and melting viruses capable of infecting humans in a cooperative fashion, has increased markedly. Hence, viruses that were limited to a particular region of the planet, or to certain population groups, have become capable of infecting humans on a pandemic scale. Some viruses not only can infect pregnant women, but also expand to the amnotic fluid and fetus.

Accelerated coronary atherosclerosis not explained by traditional risk factors in 13% of young individuals.

Importance: Most individuals who die of sudden cardiac death (SCD) display very advanced lesions of atherosclerosis in their coronary arteries. Thus, we sought to identify and characterize a putative subpopulation of young individuals exhibiting accelerated coronary artery atherosclerosis.

Objective: Our analysis of the Pathobiological Determinants of Atherosclerosis in Youth (PDAY) study-which examined 2651 individuals, obtaining quantitative measurements of traditional risk factors for coronary heart disease (CHD)-aimed to identify individuals with advanced coronary artery lesions, and to determine whether risk factors could account for such rapid disease progression, or not.

KSHV-induced ligand mediated activation of PDGF receptor-alpha drives Kaposi's sarcomagenesis.

Kaposi's sarcoma (KS) herpesvirus (KSHV) causes KS, an angiogenic AIDS-associated spindle-cell neoplasm, by activating host oncogenic signaling cascades through autocrine and paracrine mechanisms. Tyrosine kinase receptor (RTK) proteomic arrays, identified PDGF receptor-alpha (PDGFRA) as the predominantly-activated RTK in KSHV-induced mouse KS-tumors. We show that: 1) KSHV lytic replication and the vGPCR can activate PDGFRA through upregulation of its ligands PDGFA/B, which increase c-myc, VEGF and KSHV gene expression in infected cells 2) KSHV infected spindle cells of most AIDS-KS lesions display robust phospho-PDGFRA staining 3) blocking PDGFRA-signaling with N-acetyl-cysteine, RTK-inhibitors Imatinib and Sunitinib, or dominant-negative PDGFRA inhibits tumorigenesis 4) PDGFRA D842V activating-mutation confers resistance to Imatinib in mouse-KS tumorigenesis.

Fetal demise and failed antibody therapy during Zika virus infection of pregnant macaques.

Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths.

The Aging Risk and Atherosclerosis: A Fresh Look at Arterial Homeostasis.

A considerable volume of research over the last decade has focused on understanding the fundamental mechanisms for the progression of atherosclerosis-the underlying cause for the vast majority of all cardiovascular (CVD)-related complications. Aging is the dominant risk factor for clinically significant atherosclerotic lesion formation, yet the heightened impact of aging on the disease is not accounted for by changes in traditional risk factors, such as lack of physical activity, smoking, hypertension, hyperlipidemia, or diabetes mellitus. This review will examine the pathological and biochemical processes of atherosclerotic plaque formation and growth, with particular focus on the aging risk vis-a-vis arterial homeostasis.

Coronary collateralization shows sex and racial-ethnic differences in obstructive artery disease patients.

Background: Coronary collateral circulation protects cardiac tissues from myocardial infarction damage and decreases sudden cardiac death. So far, it is unclear how coronary collateralization varies by race-ethnicity groups and by sex.

Methods: We assessed 868 patients with obstructive CAD.

Allogeneic Mesenchymal Stem Cells Ameliorate Aging Frailty: A Phase II Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

Background: Aging frailty, characterized by decreased physical and immunological functioning, is associated with stem cell depletion. Human allogeneic mesenchymal stem cells (allo-hMSCs) exert immunomodulatory effects and promote tissue repair.

Methods: This is a randomized, double-blinded, dose-finding study of intravenous allo-hMSCs (100 or 200-million [M]) vs placebo delivered to patients (n = 30, mean age 75.

Twenty-First Century Diseases: Commonly Rare and Rarely Common?

Alzheimer's drugs are failing at a rate of 99.6%, and success rate for drugs designed to help patients with this form of dementia is 47 times less than for drugs designed to help patients with cancers ( www.scientificamerican.

Allogeneic Human Mesenchymal Stem Cell Infusions for Aging Frailty.

Background: Impaired endogenous stem cell repair capacity is hypothesized to be a biologic basis of frailty. Therapies that restore regenerative capacity may therefore be beneficial. This Phase 1 study evaluated the safety and potential efficacy of intravenous, allogeneic, human mesenchymal stem cell (allo-hMSC)-based therapy in patients with aging frailty.

Rationale and design of the allogeneiC human mesenchymal stem cells (hMSC) in patients with aging fRAilTy via intravenoUS delivery (CRATUS) study: A phase I/II, randomized, blinded and placebo controlled trial to evaluate the safety and potential efficacy of allogeneic human mesenchymal stem cell infusion in patients with aging frailty.

Frailty is a syndrome associated with reduced physiological reserves that increases an individual's vulnerability for developing increased morbidity and/or mortality. While most clinical trials have focused on exercise, nutrition, pharmacologic agents, or a multifactorial approach for the prevention and attenuation of frailty, none have studied the use of cell-based therapies. We hypothesize that the application of allogeneic human mesenchymal stem cells (allo-hMSCs) as a therapeutic agent for individuals with frailty is safe and efficacious.

Cardiac performance, biomarkers and gene expression studies in previously sedentary men participating in half-marathon training.

Background: The mechanisms through which exercise reduces cardiovascular disease are not fully understood. We used echocardiograms, cardiac biomarkers and gene expression to investigate cardiovascular effects associated with exercise training.

Methods: Nineteen sedentary men (22-37 years) completed a 17-week half-marathon training program.

Impact of CMS coverage decision on access to transcatheter aortic valve replacement.

Objectives: To assess the impact of the Centers for Medicare and Medicaid Services (CMS) national coverage determination (NCD) on access for patients with aortic stenosis (AS) with transcatheter aortic valve replacement (TAVR) in a tertiary care center.

Background: TAVR has given hope to patients with AS who are deemed inoperable. The effects of the NCD on access to patients with AS has not been evaluated.