Trials In Human Subjects Research Articles

Biocompatibility and Bone Regeneration by Shape Memory Polymer Scaffolds.

Biodegradable, shape memory polymer (SMP) scaffolds based on poly(ε-caprolactone) (PCL) offer unique advantages as a regenerative treatment strategy for critical-sized bone defects. In particular, a conformal fit may be achieved following exposure to warm saline, thereby improving osseointegration and regeneration. Advancing the clinical translation of these SMP scaffolds requires establishment of efficacy not only in non-loading models, but also load-bearing or load-sharing models. Thus, the present study evaluated the biocompatibility and bone regeneration potential of SMP scaffolds in a rabbit distal femoral condyle model. Two distinct SMP scaffold compositions were evaluated, a "PCL-only" scaffold formed from PCL-diacrylate (PCL-DA) and a semi-interpenetrating network (semi-IPN) formed from PCL-DA and poly(L-lactic acid) (PCL:PLLA). Semi-IPN PCL:PLLA scaffolds possess greater rigidity and faster rates of degradation versus PCL scaffolds. In vivo biocompatibility was assessed with a rat subcutaneous implantation model, whereas osseointegration was assessed with a 4 mm × 8 mm rabbit distal femoral condyle defect model. Both types of SMP scaffolds exhibited excellent biocompatibility marked by infiltration with fibrous tissue and a minimal inflammatory response. When implanted in the rabbit distal femur, both SMP scaffolds supported bone ingrowth. Collectively, these results demonstrate that the SMP scaffolds are biocompatible and integrate with adjacent host osseous tissues when implanted in vivo in a load-sharing environment. This study provides key proof-of-concept data necessary to proceed with large animal translational studies and clinical trials in human subjects.

Exploring Taurine's Potential in Alzheimer's Treatment: A Comprehensive Review.

Alzheimer's disease (AD) stands as one of the predominant neurodegenerative disorders, often culminating in dementia. Taurine, an endogenous amino acid, holds pivotal regulatory functions within the physiological milieu. Emerging evidence suggests that taurine may confer protection against the onset and progression of AD through diverse mechanistic pathways. This systematic review aims to comprehensively elucidate the multifaceted role of taurine in Alzheimer's disease.The primary objective is to assess taurine's potential as a preventative and therapeutic intervention for Alzheimer's, based on studies from 2004 to 2022. A rigorous search strategy was implemented, targeting English-language articles accessible in full text. Eligible studies were meticulously sourced from renowned databases including PubMed, PubMed Central, Science Direct, Cochrane Library, and Medline Plus. Inclusion criteria were limited to studies explicitly investigating the role of taurine in Alzheimer's disease. Our review encompasses a wealth of experimental studies conducted on murine models, collectively indicating taurine's capacity to ameliorate symptomatic presentations of Alzheimer's disease. Encouraged by these promising preclinical findings, the imperative for clinical trials in human subjects emerges. Taurine emerges as a prospective agent, offering potential mitigation of the cognitive and memory-related debility synonymous with Alzheimer's disease. This systematic review delineates a compelling body of evidence underscoring the putative neuroprotective role of taurine in Alzheimer's disease. However, it is incumbent upon the scientific community to bridge the translational gap through robust clinical investigations. Such endeavors hold promise in revolutionizing the therapeutic landscape for individuals grappling with the formidable challenges posed by Alzheimer's disease.

Abstract 7305: Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium

Abstract Background: Colorectal cancer (CRC) is a leading cause of cancer-related deaths worldwide. CRC usually develops from adenomas (CRC precursors) after a long latency period. Prevention is crucial in reducing CRC incidence and progression to cancer. Among several prevention options, calcium has been a widely considered chemo-preventative agent. Aims: Calcium plays a vital role in the regulation of epithelial cell differentiation, which is essential for epithelial growth control. Epidemiological studies have demonstrated that adequate calcium intake is crucial for protection against colonic polyp formation and colorectal cancer. However, recent interventional trials with calcium have had only modest and mixed results, and the question is how to improve efficacy. One potential strategy is to use calcium in combination with additional minerals and trace elements. Results: Our preclinical studies employing monolayer cultures with CRC cell lines and colon organoids cultures from colon polyps have shown that a calcium-rich mineral combination derived from fossilized red algae (Aquamin) is more effective than calcium alone in inducing differentiation, suppressing growth and upregulation of calcium-sensing receptor. When colonic adenomas in culture were subjected to differential proteomic analysis, Aquamin upregulated several proteins involved in proliferation suppression, DNA mismatch repair and inducing differentiation, and apoptosis. Two long-term mouse studies have demonstrated that Aquamin is more effective in suppressing polyp & CRC incidence compared to calcium alone. Based on these findings, we conducted a 90-day FDA-approved trial (a pilot study with ten subjects per arm) comparing the two interventions in human subjects at risk for CRC. Results showed that Aquamin treatment reduced proliferation and increased cell differentiation observed by immunohistochemistry. Proteomic analysis also revealed that the minerals upregulated several proteins related to growth suppression, inducing differentiation and those contributing to cell-cell and cell-matrix adhesion functions and downregulated proteins involved in proliferation and nucleic acid metabolism. Conclusion: These results provide convincing evidence that a multi-mineral combination derived from red algae can provide benefits in preventing CRC that are not seen with calcium alone. Further studies, such as a polyp-prevention trial in human subjects, are warranted to advance these CRC prevention efforts. Citation Format: Isabelle Harber, Shannon McClintock, James Varani, Muhammad N. Aslam. Chemoprevention of colorectal cancer: Role of trace minerals in conjunction with calcium [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7305.

The feasibility of a novel 3D-Printed patient specific cutting guide for extended trochanteric osteotomies

BackgroundThe extended trochanteric osteotomy (ETO) is a surgical technique utilized to expose the intramedullary canal of the proximal femur, protect the soft tissues and promote reliable healing. However, imprecise execution of the osteotomy can lead to fracture, soft tissue injury, non-union, and unnecessary morbidity. We developed a technique to create patient specific, 3D-printed cutting guides to aid in accurate positioning of the ETO and improve osteotomy quality and outcomes.MethodsPatient specific cutting guides were created based on CT scans using Synopysis Simpleware ScanIP and Solidworks. Custom 3D printed cutting guides were tested on synthetic femurs with foam cortical shells and on cadaveric femurs. To confirm accuracy of the osteotomies, dimensions of the performed osteotomies were compared to the virtually planned osteotomies.ResultsUse of the patient specific ETO cutting guides resulted in successful osteotomies, exposing the femoral canal and the femoral stem both in synthetic sawbone and cadaveric testing. In cadaveric testing, the guides allowed for osteotomies without fracture and cuts made using the guide were accurate within 6 percent error from the virtually planned osteotomy.ConclusionThe 3D-printed patient specific cutting guides used to aid in ETOs proved to be accurate. Through the iterative development of cutting guides, we found that a simple design was key to a reliable and accurate guide. While future clinical trials in human subjects are needed, we believe our custom 3D printed cutting guide design to be effective at aiding in performing ETOs for revision total hip arthroplasty surgeries.

Efficacy and Safety of Skin Radiance Collagen on Skin and Hair Matrix: A Placebo-Controlled Clinical Trial in Healthy Human Subjects.

Collagen supplements are rising in the market as collagen has been demonstrated to be an important protein in the human aging process. Also, it is safe and easily absorbed in the body. Hence the aim of this study was to examine the effectiveness and safety of a collagen and antioxidant-rich treatment compared to a placebo in relation to various skin and hair indicators in healthy adult human subjects. Forty healthy adult non-pregnant/non-lactating women (aged 38-50 years) provided their informed consent in writing before their participation. Skin Radiance Collagen (SRC) treatment and a placebo were assessed for efficacy before application on Day 1, and post-application on Days 28 and 56, to measure changes in skin elasticity, hydration, brightness, pigmentation; texture, wrinkles, dryness, smoothness, fine lines, changes in the crow's feet region; as well as hair strength and hair fall. It was observed after 56 days that therapy with SRC, compared to placebo, produced a substantial effect on reduction of wrinkle depth and fine lines by 48.11% and 39%, respectively, with p-value <0.01 in the test group. There was a 15.69% improvement in skin hydration observed and 28% reduction in hair fall with p-value <0.01. SRC, a combination of collagen with hyaluronic acid (HA), biotin, and vitamins C and E, showed a significant improvement in skin and hair health, including improvements in skin elasticity, skin hydration, reduction in crow's feet area wrinkles and fine lines, hair fall, and decrease in roughness, leading to improved skin texture. Vitamin C in the formulation also acts as a collagen builder for the body and helps in preventing oxidative stress in the body. The test treatment SRC was found to be efficacious and safe in healthy human adult subjects.

Modeling Running via Optimal Control for Shoe Design.

Shoe manufacturing technology is advancing faster than new shoe designs can viably be evaluated in human subject trials. To aid in the design process, this paper presents a model for estimating how new shoe properties will affect runner performance. This model assumes runners choose their gaits to optimize an intrinsic, unknown objective function. To learn this objective function, a simple two-dimensional mechanical model of runners was used to predict their gaits under different objectives, and the resulting gaits were compared to data from real running trials. The most realistic model gaits, i.e., the ones that best matched the data, were obtained when the model runners minimized the impulse they experience from the ground as well as the mechanical work done by their leg muscles. Using this objective function, the gait and thus performance of running under different shoe conditions can be predicted. The simple model is sufficiently sensitive to predict the difference in performance of shoes with disruptive designs but cannot distinguish between existing shoes whose properties are fairly similar. This model therefore is a viable tool for coarse-grain exploration of the design space and identifying promising behaviors of truly novel shoe materials and designs.

Pilot study of paediatric regional lung function assessment via X-ray velocimetry (XV) imaging in children with normal lungs and in children with cystic fibrosis

IntroductionCystic fibrosis (CF) is a life-limiting autosomal recessive genetic condition. It is caused by mutations in the gene that encodes for a chloride and bicarbonate conducting transmembrane channel. X-ray velocimetry...

Artificial placentas, pregnancy loss and loss-sensitive care

In this paper, we explore how the prospect of artificial placenta technology (nearing clinical trials in human subjects) should encourage further consideration of the loss experienced by individuals when their...

Improving Oral Health with Fluoride-Free Calcium-Phosphate-Based Biomimetic Toothpastes: An Update of the Clinical Evidence.

As the demand for clinically effective fluoride-free oral care products for consumers increases, it is important to document which types of toothpastes have been shown in clinical studies to be effective in improving oral health. In this review, we included different indications, i.e., caries prevention, improving periodontal health, reducing dentin hypersensitivity, protecting against dental erosion, and safely improving tooth whitening in defining what constitutes improvement in oral health. While there are several professional and consumer fluoride-containing formulations fortified with calcium-phosphate-based ingredients, this review focuses on fluoride-free toothpastes containing biomimetic calcium-phosphate-based molecules as the primary active ingredients. Several databases were searched, and only clinical trials in human subjects were included; in vitro and animal studies were excluded. There were 62 oral health clinical trials on biomimetic hydroxyapatite (HAP), 57 on casein phosphopeptide-amorphous calcium phosphate (CPP-ACP), 26 on calcium sodium phosphosilicate (CSPS, or so called Bioglass), and 2 on β-tricalcium phosphate (β-TCP). HAP formulations were tested the most in clinical trials for benefits in preventing caries, dentin hypersensitivity, improving periodontal health, and tooth whitening. Based on the current clinical evidence to date, fluoride-free HAP toothpaste formulations are the most versatile of the calcium phosphate active ingredients in toothpastes for improving oral health.

Assessing the neuroprotective efficacy of atorvastatin in traumatic brain injury: a systematic review protocol

Abstract Traumatic brain injury (TBI) is a significant public health threat, with an estimated 5.3 million people in the United States alone living with a disability related to TBI (1). The most common therapies for individuals with TBI at this time include supportive measures, direct monitoring and surgical interventions, but the treatment outcomes following TBI are still poor. Atorvastatin is one of 3-hydroxy–3-methylglutaryl coenzyme A reductase inhibitors commonly used for treatment reduction of low-density lipoprotein and relief of symptoms in cerebrovascular diseases, however, the recent randomized trials in animal models and human subjects have revealed a promising therapeutic effect for its use in the treatment of TBI that has shown a significant alleviation of neurological dysfunctions. Hence, this systematic review will streamline and provide a comprehensive avenue for understanding more about the dynamics of atorvastatin and its neuroprotective efficacy for the treatment of the severity of TBI and the improvement of functional outcomes. This systematic review will follow the 2020 PRISMA guidelines. Information sources will be obtained from electronic databases such as Pubmed, Cochrane Library, EMBASE and SCOPUS. All patients with TBI that received Atorvastatin will be included. The review will also include original peer-reviewed research articles addressing the efficacy of Atorvastatin in TBI in English. Ethical approval will not be required as there will be no human participant involvement in this study. The findings from this study will be disseminated at scientific conferences and published in a reputable peer-reviewed journal. Strengths A wide range of study types will be included increasing the pool of information.Accuracy will be upheld as two to three reviewers will independently screen titles, abstracts and full texts. Limitations Only studies in English will be included, hence studies in other languages that may be very informative will be excluded.

The Protective Effect of Oxitard on Sperm Function and Antioxidant Status in Rats Exposed to Swimming Stress.

Infertility is a significant public health issue, but its impact on quality of life and treatment efficacy is limited. Modern medicine lacks safe and effective drugs for male infertility, while traditional medicine has explored herbal extracts like Oxitard, which contains multiple extracts and oils. This study aimed to investigate the effects of Oxitard on male rats exposed to swimming (SW) stress. Albino rats weighing 220-250 g were divided into five groups: control, SW stress, and SW treated with Oxitard at low, medium, and high doses of 250, 500, and 750 mg/kg/day, respectively. The rats were subjected to SW stress for 15 days and then assessed for body weight, reproductive organ weight, testosterone, antioxidant status, sperm function, and histological changes in the testes, seminal vesicles, and vas deferens. The results showed that SW stress significantly reduced body weight, seminal vesicle weight, testosterone levels, superoxide dismutase (SOD), catalase (CAT), sperm count, sperm motility, sperm viability, and significantly increased malondialdehyde (MDA) levels. The testes of the SW-stress group rats also showed a significant decrease in spermatogenesis and the number of seminiferous tubules containing sperm. In contrast, treatment with Oxitard, especially at the highest dose, demonstrated potent free radical scavenging activity, recovering antioxidant status, and sperm function. SW stress led to decreased sperm function, antioxidant status, and increased lipid peroxidation (LPO) in male rats. Oxitard treatment, particularly in high doses, showed a potential role as a free radical scavenger in treating oxidative stress (OS)-associated male infertility. Further studies are needed to investigate the individual components of Oxitard and conduct clinical trials in human subjects.

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Contextual Vulnerability Should Guide Fair Subject Selection in Xenotransplantation Clinical Trials

Zinc as an inhibitor of NMDA receptor can exhibit antidepressant effect

Background : New antidepressant strategies are needed, due to unsatisfactory clinical efficacy and many side effects of commonly used drugs. Recent studies linking the pathophysiology of depression with glutamatergic imbalance. There is hyperactivity of the main excitatory system (glutamatergic) to its inhibition (GABAergic). N-methyl D-aspartate (NMDA) receptors as a part of glutamatergic synapses are potential targets for intervention. Antagonist administration for glutamatergic systems, such as zinc, can exhibit antidepressant effects.&#x0D; Objective : To observe the effect of zinc administration on NMDA receptors in depressed subjects&#x0D; Methods : In this paper, we provide a literature review. The method to achieve the objective consists of using literature exploration, which was conducted from February to June 2022 by searching the relevant studies from several databases.&#x0D; Results : Study trials both in human and animal subjects reveal that depression is associated with a lower concentration of zinc. Comparison between the lowest zinc intake with the highest zinc intake had significantly lower incidence of developing depression. Dietary zinc deficiency induces depression along with upregulation of the NMDA receptor complexes. Zinc’s antidepressant effects might be mediated through its action reducing NMDA channel-opening frequency.&#x0D; Conclusions : The presence of zinc may downregulate the glutamate response in binding to NMDA receptors. Because of numerous studies about the connection between zinc and depression, it seems that zinc may have the potency to develop new antidepressants. Since the capability of zinc administration to reduce depressive symptoms, it is expected leading to increased medication adherence, lower costs and better outcomes.

A Systematic Review on Clinical Research and Approval Process

Drug discovery is a key step or process by which lead molecule is been optimized for further preclinical and clinical trial studies. Drug development process involves target identification, target validation, lead identification, and lead optimization. Once the lead molecule is optimized the HIT compound is been analyzed further in preclinical trial in animals and clinical trial in human subjects. The development of a new drug till marketing authorization should gone through several stages in order to make the drug safe, effective and should posses best quality to get approve for applicable regulatory requirements. The overall theme of our article is to review and state the process from drug discovery to approval for marketing of drug. The process from drug discovery till marketing authorization is time taking, complex and expensive so each target should be consider for development of new drug and new research tools must be used for any new drug development process. It takes around 10-15 years and US$ 1 billion for a new lead compound to make it as a medicine and to get marketing approval for general public use. On an average million lead molecules are been scrutinized to make a HIT compound, so that it can be use for further preclinical and clinical studies to make it available in market. This article provides a brief outline on stages from drug development to clinical research.&#x0D;

Targeted Temperature Management in Cardiac Arrest: An Updated Narrative Review.

The established benefits of cooling along with development of sophisticated methods to safely and precisely induce, maintain, monitor, and reverse hypothermia have led to the development of targeted temperature management (TTM). Early trials in human subjects showed that hypothermia conferred better neurological outcomes when compared to normothermia among survivors of cardiac arrest, leading to guidelines recommending targeted hypothermia in this patient population. Multiple studies have sought to explore and compare the benefit of hypothermia in various subgroups of patients, such as survivors of out-of-hospital cardiac arrest versus in-hospital cardiac arrest, and survivors of an initial shockable versus non-shockable rhythm. Larger and more recent trials have shown no statistically significant difference in neurological outcomes between patients with targeted hypothermia and targeted normothermia; further, aggressive cooling is associated with a higher incidence of multiple systemic complications. Based on this data, temporal trends have leaned towards using a lenient temperature target in more recent times. Current guidelines recommend selecting and maintaining a constant target temperature between 32 and 36°C for those patients in whom TTM is used (strong recommendation, moderate-quality evidence), as soon as possible after return of spontaneous circulation is achieved and airway, breathing (including mechanical ventilation), and circulation are stabilized. The comparative benefit of lower (32-34°C) versus higher (36°C) temperatures remains unknown, and further research may help elucidate this. Any survivor of cardiac arrest who is comatose (defined as unarousable unresponsiveness to external stimuli) should be considered as a candidate for TTM regardless of the initial presenting rhythm, and the decision to opt for targeted hypothermia versus targeted normothermia should be made on a case-by-case basis.

Evaluation of the Preliminary Safety, Tolerability and Colonisation Efficacy of Topical Probiotic Formulations Containing Micrococcus luteus Q24 in Healthy Human Adults

Probiotics developed for topical applications in humans have the potential to beneficially modulate microbial imbalances on the skin surface and thereby improve skin health. This study was conducted to determine whether topical formulations containing the human skin commensal Micrococcus luteus strain Q24 (BLIS Q24) are safe, tolerable and efficacious when used by healthy human subjects. M. luteus Q24 was assessed in vitro for haemolytic activity and its antibiotic susceptibility profile. Formulations of strain Q24 were evaluated for the preliminary safety and tolerability in healthy human participants. Forty-seven adults were randomly assigned to four single-site, single-blind randomised placebo or baseline controlled or active-controlled trials. Skin swab samples were collected for differential viable counts to monitor levels of probiotic colonisation. M. luteus Q24 was found to be non-haemolytic and susceptible to commonly used antibiotics. The M. luteus Q24 formulations were safe and tolerable and &gt;90% of the participants reported improvements from baseline in the appearance (e.g., radiance and hydration) of their treated skin. Additionally, participants observed a reduction in pore size, skin clarity and enhanced skin softness. No adverse effects were reported. A dose-related significant increase was observed in the levels of M. luteus Q24 isolated from skin swabs of the probiotic-treated subjects. Placebo-controlled trials in human subjects involving the topical application of different doses of M. luteus Q24 formulations were supportive of the safety, tolerability and efficacy of probiotic M. luteus Q24. Self-reported skin health assessments by the subjects indicated that M. luteus Q24 has good potential as a probiotic for improving skin health quality.

The interplay between the gut-brain axis and the microbiome: A perspective on psychiatric and neurodegenerative disorders.

What is the effect of our gut microbial flora on brain? Does the gut microbiome have any role in the causation of psychiatric and neurodegenerative diseases? Does the effect of gut microbiota traverse the gut-brain axis? Questions like these have captured the interest and imagination of the scientific community for quite some time now. Research in the quest for answers to these questions, to unravel the potential role of the microbiota inhabiting the gut in controlling brain functions, has progressed manifold over the last two decades. Although the possibility of microbiome as a key susceptibility factor for neurological disorders viz. Parkinson's disease, Alzheimer's disease, multiple sclerosis, and autism spectrum disorder has bolstered by an increase in the clinical and preclinical evidence, the field is still in its infancy. Given the fact that the diversity of the gut microbiota is affected by various factors including the diet and exercise, the interpretation of such data becomes all the more difficult. Also, such studies have been mostly conducted on animal models, so there is a need for randomized controlled trials in human subjects, corroborated by longitudinal studies, to establish if modulating the gut microbiota can unravel novel therapeutic interventions. Exploring the genomic, metagenomic and metabolomic data from clinical subjects with psychiatric and neurological diseases can prove to be a helpful guide in individual treatment selection.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

Aspects of the CPRRD Affecting Xenotransplantation Research in Human Heart-beating Brain-dead Decedents.

Anti-cancer Effects of Methotrexate in Combination With Melissa officinalis on HeLa Cancer Cell Line

Objectives: One of the well-accepted beliefs about natural products, considering the advances of recently appearing new edges and features of herbal medicine, is paying more attention to cancer treatments. However, they have not been properly studied with reasonable/reliable clinical trials in human subjects in most cases. Therefore, seeking in vitro effects of herbs like Melissa officinalis (MO) in cancer therapy to identify the involved possible mechanism in conjugation with configurative/morphological aspects of treated cells seems quite necessary. In this study, we evaluated the co-treatment effect of anti-cancer drug methotrexate (MTX) and MO on HeLa cancer cells. Methods: MTT assay was applied to assess the quantitative cytotoxicity effect of both MTX and Mo. Apoptosis assay via flow cytometry was used to determine the amount of apoptotic and necrotic cells. To further investigate the anti-cancer effects, DAPI staining and DNA ladder assays are used qualitatively to detect changes in the nuclei of cells that are a sign of apoptosis occurring and morphological modifications of DNA. Results: MTX and MO mixture showed high cytotoxicity and apoptosis rate compared to untreated cells. Furthermore, the morphological changes of MTX and MO mixture were more evident than that of single MO, MTX, and control groups. Conclusions: These data regarding cell growth reduction and apoptosis induction in HeLa cancer cells showed that MTX and MO mixture can be an appropriate platform for cancer therapy.

Xenotransplantation: A New Era.

Organ allotransplantation has now reached an impassable ceiling inherent to the limited supply of human donor organs. In the United States, there are currently over 100,000 individuals on the national transplant waiting list awaiting a kidney, heart, and/or liver transplant. This is in contrast with only a fraction of them receiving a living or deceased donor allograft. Given the morbidity, mortality, costs, or absence of supportive treatments, xenotransplant has the potential to address the critical shortage in organ grafts. Last decade research efforts focused on creation of donor organs from pigs with various genes edited out using CRISPR technologies and utilizing non-human primates for trial. Three groups in the United States have recently moved forward with trials in human subjects and obtained initial successful results with pig-to-human heart and kidney xenotransplantation. This review serves as a brief discussion of the recent progress in xenotransplantation research, particularly as it concerns utilization of porcine heart, renal, and liver xenografts in clinical practice.