Increasing uptake of colon cancer screening in a medically underserved population with the addition of blood-based testing.

BACKGROUND: Adherence to colorectal cancer screening in the United States is suboptimal, particularly in medically underserved populations due to significant barriers to care. Unique accessible, low-cost, and non-invasive screening tests for this population could greatly benefit current rates. In this article, we assess patient preference and the impact of offering a blood-based test on screening rates in a cost-free health fair setting from April 2017 to April 2019. METHODS: Participants who met colorectal cancer screening eligibility criteria set forth by the United States Preventive Services Task Force were recommended to attend the colon cancer screening station. Those participants who elected to attend were offered various, accepted screening methods, and if they declined, were offered alternative blood-based testing. Screening rates, test outcomes, and the rate of follow up completion of colonoscopy were measured and compared with historic screening outcomes. RESULTS: Of 1401 participants who were recommended to attend, 640 (45.7%) participants were evaluated at the colon cancer screening station, of whom 460 were eligible for testing. Amongst these, none selected colonoscopy, 30 (6.5%) selected fecal immunochemical testing, and 430 (93.5%) selected blood-based testing. Only 2 participants returned the fecal immunochemical tests. In the blood test cohort, 88 were positive and 20 received a follow up colonoscopy. CONCLUSIONS: Based on this assessment, blood-based testing is an effective method to increase screening rates in medically underserved populations, though efforts to further improve access to follow up colonoscopy are necessary.

Identifiable biomarker and treatment development using HIV-1 long term non-progressor sera.

BACKGROUND: HIV-infected long-term non-progressor (LTNP) subjects can prevent viral replication and may harbor useful information for the development of both antibody and active vaccination treatments. In this study we used LTNP sera to examine the epitopes presented to the gp160 protein, and from this procedure we hope to elucidate potential biomarkers pertaining to the level of resistance a patient may have in developing AIDS after infection with HIV. We used five clinical sera samples from LTNP patients to identify common epitopes by ELISA; peptides with high binding to sera were selected and analyzed for conservation among HIV clades. Antibodies were generated against one identified epitope using a chimeric peptide in BALB/c mice, and both the sera from these mice and LTNP sera were tested for viral inhibition capabilities. RESULTS: A monoclonal antibody, CL3, against one identified epitope was used to compare these epitopes neutralizing capability. LTNP sera was also studied to determine chemokine/cytokine changes in these patients. The sera from LTNP patients 2, 3, 4, and 5 were identified as having the highest titers, and also significantly inhibited syncytia formation in vitro. Finally, the protein cytokine array demonstrated that I-309 and IGFBP-1 decreased in LTNPs, but levels of TIMP-1 and NAP-2 increased significantly. CONCLUSIONS: Our results indicate that the use of LTNP samples may be a useful for identifying further anti-viral epitopes, and may be a possible predictor for determining if patients show higher resistances of converting the HIV infection to AIDS.

Project T-SHARP: study protocol for a multi-site randomized controlled trial of tele-harm reduction for people with HIV who inject drugs.

BACKGROUND: The resurgence of HIV outbreaks and rising prevalence among people who inject drugs (PWID) remain exigent obstacles to Ending the HIV Epidemic in the USA. Adapting a low threshold, comprehensive treatment model for PWID with HIV can leverage syringe services programs (SSPs) to increase availability and accessibility of antiretrovirals (ART), medications for opioid use disorder (MOUD), and hepatitis C cure. We developed Tele-Harm Reduction, a telehealth-enhanced, harm reduction intervention delivered within an SSP venue. METHODS: The T-SHARP trial is an open-label, multi-site, randomized controlled superiority trial with two parallel treatment arms. Participants (n=240) recruited from SSPs in Miami, Ft. Lauderdale, and Tampa, Florida, who are PWID with uncontrolled HIV (i.e., HIV RNA>200) will be randomized to Tele-Harm Reduction or off-site linkage to HIV care. The primary objective is to compare the efficacy of Tele-Harm Reduction for initiation of ART at SSPs vs. off-site linkage to an HIV clinic with respect to viral suppression across follow-up (suppression at 3, 6, and 12 months post randomization). Participants with HIV RNA<200 copies/ml will be considered virally suppressed. The primary trial outcome is time-averaged HIV viral suppression (HIV RNA <200 copies/ml) over 3-, 6-, and 12-month follow-up. Secondary outcomes include initiation of MOUD measured by urine drug screen and HCV cure, defined as achieving 12-week sustained virologic response (negative HCV RNA at 12 weeks post treatment completion). A cost-effectiveness analysis will be performed. DISCUSSION: The T-SHARP Trial will be the first to our knowledge to test the efficacy of an innovative telehealth intervention with PWID with uncontrolled HIV delivered via an SSP to support HIV viral suppression. Tele-Harm Reduction is further facilitated by a peer to support adherence and bridge the digital divide. This innovative, flipped healthcare model sets aside the traditional healthcare system, reduces multi-level barriers to care, and meets PWID where they are. The T-SHARP trial is a pragmatic clinical trial that seeks to transform the way that PWID access HIV care and improve HIV clinical outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT05208697. Trial registry name: Tele-Harm Reduction. Registration date: January 26, 2022.

An Open-Label, Prospective Study Evaluating the Clinical and Immunological Effects of Higher Dose Granulocyte Colony-Stimulating Factor in ALS.

OBJECTIVE: We evaluated the safety and tolerability of higher-dose granulocyte colony-stimulating factor (G-CSF) in patients with amyotrophic lateral sclerosis. In addition, rates of disease progression and serum G-CSF levels and other immunological and hematological markers were measured. METHODS: Three patients with advanced amyotrophic lateral sclerosis were treated with G-CSF subcutaneously at 5 µg/kg twice daily for 5 consecutive days monthly for 4-12 months. Patients were monitored for adverse effects, and disease progression was assessed with ALSFRS-R and other measures. RESULTS: Patients tolerated higher-dose G-CSF well with no serious adverse events. Adverse effects were mild to moderate with musculoskeletal pain and malaise being most often reported. No significant change in the rate of disease progression was noted for ALSFRS-R or other measures. Bone marrow progenitor cells were rapidly mobilized for a duration of approximately 9 days with transient and variable effect on cytokines. CONCLUSIONS: Higher-dose G-CSF was well tolerated in this cohort with no apparent effect on disease progression up to 1 year.

Recent Advances in Understanding the Pathogenesis of Cardiovascular Diseases and Development of Treatment Modalities.

Cardiovascular Diseases (CVDs) are a leading cause of morbidity and mortality worldwide. The underlying pathology for cardiovascular disease is largely atherosclerotic in nature and the steps include fatty streak formation, plaque progression and plaque rupture. While there is optimal drug therapy available for patients with CVD, there are also underlying drug delivery obstacles that must be addressed. Challenges in drug delivery warrant further studies for the development of novel and more efficacious medical therapies. An extensive understanding of the molecular mechanisms of disease in combination with current challenges in drug delivery serves as a platform for the development of novel drug therapeutic targets for CVD. The objective of this article is to review the pathogenesis of atherosclerosis, first-line medical treatment for CVD, and key obstacles in an efficient drug delivery.

Recent treatment modalities for cardiovascular diseases with a focus on stem cells, aptamers, exosomes and nanomedicine.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Due to the significant impact of CVD on humans, there is a need to develop novel treatment modalities tailored to major classes of cardiac diseases including hypertension, coronary artery disease, cardiomyopathies, arrhythmias, valvular disease and inflammatory diseases. In this article, we discuss recent advancements regarding development of therapeutic strategies based on stem cells, aptamers, exosomes, drug-eluting and dissolvable stents, immunotherapy and nanomedicine for the treatment of CVD. We summarize current research and clinical advances in cardiovascular therapeutics, with a focus on therapies that move beyond current oral- or sublingual-based regimens. This review article provides insight into current research and future treatment strategies that hold a great relevance for future clinical practice in pursuit of improving quality of life of patients suffering from CVD.

Manual acupuncture at the SJ5 (Waiguan) acupoint shows neuroprotective effects by regulating expression of the anti-apoptotic gene Bcl-2.

Acupuncture at the SJ5 (Waiguan) acupoint has neuroprotective effects in cerebral infarction, but the underlying mechanism remains poorly understood. Here, we analyzed gene expression in healthy rat cerebellum using a pathway-focused DNA microarray to screen 113 genes associated with 18 signal transduction pathways. After 20 minutes of acupuncture at SJ5, the expression of Bcl-2 and Birc1b mRNA was markedly increased. This was confirmed by real-time reverse transcription PCR. Furthermore, western blot analysis showed that Bcl-2 protein expression remained high in the cerebellum until at least 2 hours after cessation of acupuncture. These findings indicate that acupuncture at SJ5 exerts neuroprotective effects by regulating the expression of anti-apoptotic gene Bcl-2.

Polymer-Encapsulated Aß Peptide Fragments as an Oligomeric-Specific Vaccine for Alzheimer's Disease.

Vaccination is regarded as one of the most cost-effective and reliable methods for combating disease. We have developed a new method for an oligomeric Aß-specific AD vaccination using polymer micelle-encapsulated peptide fragments, which overcome many problems of vaccination associated with the direct use of the Aß1­42 peptide. We studied different encapsulated forms of shortened Aß peptides with and without the entire T cell epitope in an APP/PS1 mouse model. After two inoculations with encapsulated Aß fragments, antibodies were produced in all mice with antibody titer greater than 1:12,800. No anti-polymer antibodies were detected after five inoculations, and none of the injected mice showed any adverse effects throughout experimentation. Anti-Aß antibodies from our polymer-encapsulated vaccine were able to bind to A plaques in the brain of our mice, and were able to specifically recognize oligomeric Aß. Our results suggest that the safety and efficacy issues previously encountered in other Aß vaccination trials may be successfully addressed by using micelle-encapsulated peptides. These shorter Aß fragments are also easier to synthesize and more cost-effective than the highly hydrophobic full-length Aß1­42 peptide.

The potential therapeutic effects of THC on Alzheimer's disease.

The purpose of this study was to investigate the potential therapeutic qualities of Δ9-tetrahydrocannabinol (THC) with respect to slowing or halting the hallmark characteristics of Alzheimer's disease. N2a-variant amyloid-ß protein precursor (AßPP) cells were incubated with THC and assayed for amyloid-ß (Aß) levels at the 6-, 24-, and 48-hour time marks. THC was also tested for synergy with caffeine, in respect to the reduction of the Aß level in N2a/AßPPswe cells. THC was also tested to determine if multiple treatments were beneficial. The MTT assay was performed to test the toxicity of THC. Thioflavin T assays and western blots were performed to test the direct anti-Aß aggregation significance of THC. Lastly, THC was tested to determine its effects on glycogen synthase kinase-3ß (GSK-3ß) and related signaling pathways. From the results, we have discovered THC to be effective at lowering Aß levels in N2a/AßPPswe cells at extremely low concentrations in a dose-dependent manner. However, no additive effect was found by combining caffeine and THC together. We did discover that THC directly interacts with Aß peptide, thereby inhibiting aggregation. Furthermore, THC was effective at lowering both total GSK-3ß levels and phosphorylated GSK-3ß in a dose-dependent manner at low concentrations. At the treatment concentrations, no toxicity was observed and the CB1 receptor was not significantly upregulated. Additionally, low doses of THC can enhance mitochondria function and does not inhibit melatonin's enhancement of mitochondria function. These sets of data strongly suggest that THC could be a potential therapeutic treatment option for Alzheimer's disease through multiple functions and pathways.