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May 2026 DOI 10.14302/issn.2574-4518.jsdr-25-5773
Introduction Sleep quality is a fundamental determinant of human health and well-being. Modified Intravascular Laser Irradiation of Blood (ILIB), a non-invasive therapeutic modality, has emerged as a potential intervention for sleep-related disturbances. Proposed mechanisms include reduced blood viscosity and platelet aggregation, activation of superoxide dismutase, increased oxygen bioavailability, enhanced microcirculation, elevated serotonin levels, and decreased cortisol concentrations—physiological processes intricately involved in sleep regulation, mood modulation, and the stress response. Objective To evaluate the effects of Modified Intravascular Laser Irradiation of Blood (ILIB) on sleep quality in individuals with self-reported sleep disturbances. Methods A randomized, placebo-controlled clinical trial was conducted with participants who reported poor sleep quality. Subjects were randomly assigned to one of two groups: the intervention group received ILIB using a 660 nm red laser, while the control group received a placebo treatment (light emission with sub-therapeutic power, <1 mW). Both groups underwent the same treatment schedule. Sleep quality was assessed at baseline and after six treatment sessions using the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS). Results Participants in the ILIB group showed statistically significant improvements in the primary outcome of global sleep quality. PSQI scores decreased from 10.24 at baseline to 6.47 post-treatment. ESS scores showed a non-significant change from 10.44 to 10.12. These results suggest enhanced overall sleep quality and reduced sleep latency, although the observed reduction in daytime sleepiness did not reach statistical significance. Conclusion Modified Intravascular Laser Irradiation of Blood appears to be a promising non-invasive approach for improving sleep quality. The clinical outcomes observed are comparable to those reported in both pharmacological and behavioral sleep interventions, particularly in terms of PSQI improvements. These preliminary findings support the need for further research to clarifyunderlying mechanisms, optimize treatment parameters (e.g., dosimetry and duration), and expand outcome assessments to include biomarkers and polysomnographic data.
Nov 2025 DOI 10.14302/issn.2476-1710.jdt-25-5775
A number of developmental factors increase risk for adolescent rumination. This particular kind of repetitive negative thinking pattern often begins in the context of familial stressors and parental modeling. Though rumination can be effectively targeted with rumination-focused cognitive behavioral therapy (RF-CBT), it is unknown whether caregiver-child co-rumination (1) affects caregiver views of their child’s psychopathology, (2) or interferes with youth rumination- focused treatment. The present study uses data from a randomized clinical trial of RF-CBT to examine whether caregiver-child co-rumination, or caregivers’ own rumination patterns, are associated with bias in parental perception of their adolescent’s depression symptoms. We also examine if co-rumination scores at baseline moderate rumination scores for youth at treatment termination, and whether treatment effects dampen or decay more significantly post-treatment among youth with higher caregiver-child co-rumination. Youth (N = 76) were randomized to either 10-14 sessions of RF-CBT (n = 38) or treatment as usual (TAU; n = 38) and completed interviews and surveys at pre-treatment baseline, post-treatment, and 3-, 6-, 9-, and 12-month follow up. Results indicate that neither caregiver rumination nor co-rumination scores bias caregivers’ views of their child’s depression symptoms. In terms of reduction in child’s rumination scores, estimated treatment effects were larger for patients with higher baseline co- rumination scores, and there was no statistically significant difference in treatment effect decay over time in high versus low co-rumination groups. Results indicate co-rumination overall does not dampen the effect of RF-CBT, and those experiencing the highest levels of co-rumination may benefit most from treatment.
Jun 2024 DOI 10.14302/issn.2379-7835.ijn-24-5117
In this study, the efficacy and safety of DKB-131 (extract of Siraitiagrosvenorii) in adults of both genders presenting mild symptoms of knee arthritis were evaluated in comparison to a placebo. This clinical trial was randomized, double-blind, multicenter, and lasted for 12 weeks. A total of 120 participants with Visual Analogue Scale (VAS) scores of 30 mm or higher in the knee area and Kellgren & Lawrence Grade I or II knee arthritis on X-ray were enrolled, with 60 subjects randomized to receive DKB-131 and 60 subjects receiving placebo. Following 12 weeks of consumption, the change in K-WOMAC total score assessed in the per protocol (PP) set revealed a reduction of 21.86±15.98 points in participants who received DKB-131 (p<0.0001), whereas those in the placebo group exhibited a reduction of 14.92±16.66 points (p<0.0001). This demonstrated a statistically significant difference between the test groups (p=0.0389). Additionally, significant differences were observed between the DKB-131 and placebo groups in the changes in K-WOMAC pain (p=0.0157) and physical function (p=0.0447). For the secondary efficacy endpoint, the change in Visual Analogue Scale (VAS) scores, analyzed in the PP set after 12 weeks of consumption, the test group showed a reduction of 17.82±13.80 mm (p<0.0001), while the control group exhibited a reduction of 11.81±13.99 mm (p<0.0001), indicating a statistically significant difference between the test groups (p=0.0359). Safety evaluations including hematological tests, biochemical tests, and urinalysis revealed no clinically significant differences between the consumption groups. Additionally, vital signs (pulse, blood pressure) and anthropometric measurements (body weight) did not exhibit clinically significant differences between the consumption groups, confirming the safety of DKB-131. We propose that the consumption of DKB-131 is safe for humans and may contribute to joint health. Trial registration (CRIS.NIH.go.Kr): KCT0008527
Oct 2022 DOI 10.14302/issn.2381-862X.jwrh-22-4315
Background Polycystic ovary syndrome (PCOS) is a serious multifactorial disorder. This study intended to assess the effect of cinnamon supplementation on estradiol level, and fasting- and two-hour (2 hpp) insulin and sugar levels in women with PCOS. Material and Methods This study was a double-blinded randomized clinical trial (RCT), conducted between January 2019 until December 2020, at Gynecology Clinic Sarem Women’s Hospital in Tehran, Iran. Patients with PCOS, 130 subjects (65 person/ group) were diagnosed using Rotterdam diagnostic criteria. All participants received daily treatment consisting of 1500 mg metformin and 1000 mg cinnamon per day for 12 weeks. An evaluation of serum AMH level was conducted before and after the completion of therapy. Results Cinnamon supplementation significantly reduced the estradiol, fasting glucose and 2hpp glucose, fasting insulin and 2 hpp insulin, BMI and weight levels after intervention. The highest reduction was observed in fasting glucose, 2 hpp insulin, and estradiol groups after intervention (P<0.05). There was a significant difference between the means of BMI (P<0.01), fasting sugar (P<0.01), and 2 hpp glucose (P<0.01) before and after intervention. Conclusion Cinnamon supplementation, as a safe herbal product, can be prescribed with metformin to improve the symptoms and complications of PCOS.
Mar 2017 DOI 10.14302/issn.2474-3585.jpmc-16-1161
There Is A Gap Between What We Know And What We Do, Such As Knowing What We Should Eat And What We Actually Eat, A So-Called “Attitude/Behavior Gap”. It Is Not Necessary To Go From A Change In Attitude To A Change In Behavior. It Is Possible To Do The Opposite; In Other Words, It Is Possible To Go From A Change In Behavior To A Change In Attitude. The Objective Of This Paper Is To Describe And Explain The Concept Of Dietary Advice On Prescription (DAP) And Present The Reasons And Evidences For The DAP Messages. Dietary Advice On Prescription (DAP) Starts With Discussing Behaviors Related To Dietary Habits And Then Goes From Behaviors Towards Attitudes. DAP Is A Theory-Based Pedagogical Model That Deals With Behaviors Related To Why, How And When We Eat, Rather Then What We Eat. The DAP Model Is A Method That Quickly Leads The Client Onto A Track That Yields Autonomy, Respects The Client’s Integrity, Gives Confirmation, Emphasizes The Delight And Pleasure Of Eating, Stimulates Discussions And Gives The Client The Initiative In These Discussions. In A Clinical Situation, The Counsellor Lays Out The DAP Postcards On A Table And The Client Picks One Card (Or Several) That Feels Relevant And Interesting For The Client To Discuss. Together They Make An Agenda For The Discussion Such As, For Instance, In What Order To Discuss The DAP Postcards. The Counsellor Asks In An Open Manner With A Motivational Interview (MI) Spirit Why The Client Has Chosen The Particular Card(S). The Client Explains, Elaborates, Turns And Twist About The Choices He/She Has Made. The Results Of The First Published Qualitative Study Of This Two-Year Randomized Controlled Trial Demonstrate That The Participants Found The Concept Valuable.
Feb 2014 DOI 10.14302/issn.2324-7339.jcrhap-13-211
Recruitment of couples is important for study success. The multi-centered HPTN 052 clinical trial was designed to evaluate whether immediate versus delayed use of ART by HIV-infected individuals would reduce transmission of HIV to their HIV-uninfected partners. The objective of this study was to retrospectively compare several approaches for community recruitment at our site in Kisumu, Kenya based on a) feedback from recruitment staff, b) associated cost, and c) number of eligible couples enrolled. A secondary objective was to assess the discordant couples’ acceptability of the community recruitment approaches relative to the a) main recruitment venues, b) educational materials, and c) local language best suited for explaining the trial. 241 couples were screened for eligibility using nine recruitment approaches. We compared the approaches used for the 60 couples found to be eligible to those used for the 56 ineligible couples for whom that information was available. Analyses for association were carried out. In-depth interviews were conducted with 20 staff and 29 discordant couples. Records were kept of the costs associated with each approach. Overall, staff interviews revealed that acceptability of the approaches was high. Challenges were present with all approaches ranging from one member of the couple not wanting to reveal their positive HIV status to their partner (Patient Support Center or PSC approach), to not finding people at home (home based counseling and testing or HBCT approach). The PSC and the HBCT recruitment approaches were the most effective in terms of recruiting eligible participants. There was an overall significant difference between the proportion of eligible and ineligible participants among the 9 approaches (χ2 (8) =33.5; p<0.0001). Analyses for association showed that the PSC approach resulted in attracting a greater proportion of couples who were eligible than ineligible (χ2 (1) =6.6; p=0.016). The cost for the PSC approach was less than one-third that of the HBCT approach. All discordant couples interviewed found the two main recruitment venues (PSC and their home) acceptable. Among couples who saw the educational materials, the majority found them useful (poster 72.7%; pamphlet 90.9%; flyer 88.9%). All couples found the language they were told about the study acceptable. The evaluation of recruitment approaches indicated that working with local partners, specifically the PSC staff and HBCT staff, was the most effective way to recruit eligible discordant couples. A focus on collaborations and partnerships between research and clinical organizations will help study recruitment efforts. Disclaimer: The findings and conclusions in this report are those of the authors and do not necessarily represent the views of their respective institutions. Funding for this substudy was provided by the Kenya Medical Research Institute (KEMRI) through a cooperative agreement with the U.S. Centers for Disease Control and Prevention.
May 2026 DOI 10.14302/issn.2572-3030.jcgb-26-6307
The development of tumor biomarkers derived from blood, or its components, has become pivotal in advancing early cancer diagnosis. Malignant transformations induce cancer-specific alterations in the transcriptome, proteome, and secretome of tumor cells. Recent studies highlighted similar alterations in peripheral blood mononuclear cells (PBMCs) in cancer patients, which appear to mirror the state of transformation in tumor cells. These findings suggest an intercellular communication–driven mechanism rather than a systemic inflammatory response and, in addition to current ctDNA-based liquid biopsy biomarkers, point to a novel, simple, and highly robust approach for the early detection of cancer. Using this phenomenon to advance PBMC-based biomarker development, it will be essential to achieve 3D in vitro tumor models that reproduce a highly physiological tumor microenvironment (TME). Likewise, more enhanced 3D ex vivo models are required to enable the replication of cell-to-cell and organ-to-organ communication. These systems will guide the self-organization of mixed microenvironments derived from different tissues and enable them to accurately reproduce the molecular connections underlying these alterations. In this study, an innovative new modular 3D co-culturing approach was used to expose PBMCs to lung tumoroids, under physiologically relevant conditions. Changes in DNA fragmentation of PBMCs in the presence of lung cancer were quantified and used as a biomarker. To validate the predictiveness of this biomarker, our results were compared with clinical data from a clinical evaluation study. Similar to the clinical trial observations, PBMCs, when exposed to lung tumoroids, showed a significantly lower level of DNA fragmentation (37%). This modular 3D co-culturing model showed a predictiveness of the clinical data of > 90%, demonstrating its power to monitoring cell-to-cell communication effects and support the development of blood-based biomarkers.
May 2026 DOI 10.14302/issn.2641-4538.jphi-26-6161
Objectives Motor fluctuations and non-motor disorders not manageable by first-line treatments in advanced Parkinson's disease require continuous dopaminergic stimulation strategies such as subcutaneous infusions of apomorphine (APO) or foslevodopa/foscarbidopa (FLD/FCD). A Budget Impact Analysis (BIA) was performed to estimate the cost difference between both treatments assuming equivalent clinical efficacy and safety. Material and methods The efficacy results of pivotal clinical trials at 12 and 52 weeks of treatment and the safety profile of APO vs FLD/FCD were compared, based on latest scientific publications and other available clinical data. A comparative BIA was performed, based on estimated annual drug treatment costs at Spanish published prices. Results The efficacy of APO (16 h/day) and FLD/FCD (24 h/day) in reduction of OFF hours (2.47 vs 2.75, 12 weeks; 3.66 vs 3.50, 52 weeks; respectively) and increase of ON hours without disabling dyskinesias (2.77 vs 2.72, 12 weeks; 3.31 vs 3.80, 52 weeks; respectively) could be considered clinically equivalent, as well as their safety profiles. However, a significant discrepancy is observed in the costs of the aforementioned alternatives. Considering published prices and the average dose reported in the literature, in Spain the annual cost of APO would be €13,980 compared to €55,198 for FLD/FCD. Consequently, the financial resources required for the treatment of FLD/FCD would enable the treatment of approximately three to four patients with APO. The BIA indicated the potential for annual savings in more than €2,500 million, considering a total target population of over 60,000 patients per year. Finally, an univariant sensitivity analysis was performed, considering a scenario in which the hospital acquisition cost of FLD/FCD decreased between 20%-30% (€44,159- €38,638/year). In this scenario, the total annual savings range between €1,875-€1,532 million per year. Conclusions Overall APO is more efficient than FLD/FCD, as it provides similar clinical efficacy at a lower treatment cost. The selection of an appropriate treatment option is to be determined by clinical criteria and patient characteristics, but cost evaluation should be considered to select the most cost-effective therapeutic option.
Dec 2025
Background Research and drug development industries have multiphase drug screening procedures, which can be debated. As a result, harmful products may still reach for public health service delivery due to vulnerabilities in the process. Main body A wide range of test compounds have delayed manifestation of undesired effect on the study subject, with the time to undesired effects after acute exposure being weeks and months. Acute toxicology in a preclinical trial also has limited clinical value as its lethal dose is the endpoint for a conclusion, and death sometimes occurs after a scheduled period of acute toxicology. Countless resources are wasted, and numerous new drugs are introduced into the pharmaceutical market with assumed safety analysis every year due to vulnerable multi-procedures in preclinical trials. The principal use of collected data from a preclinical trial is to support regulatory categorization and harmful labelling decisions. However, the data can also be used to derive safe use threshold levels, which may lead to the use of unsafe material. The criteria for classification and labelling also differ among countries, sometimes among authorities within the same country. The fundamental concept of toxicology states that ‘all chemical substances are potential poisons depending on the amount and duration of exposure. However, the toxic property of a test compound cannot be created or eliminated by simply the amount administered to study animals. Conclusion All xenobiotics are poisons at any amount with different severity that can be calculated using biological parameters.
Apr 2024 DOI 10.14302/issn.2997-2086.jfs-23-4651
This article has been retracted on April 10, 2025. VIEW THE RETRACTION NOTICE (https://doi.org/10.14302/issn.2997-2086.jfs-25-5857) Myelomeningocele (MMC), a class of spina bifida is a type of neural tube defect. According to the U.S. Centers for Disease Control and Prevention, each year approximately 1,400 babies born in the United States have spina bifida. The disease manifests with the lack of skin and bone covering the caudal part of the spinal cord. The patient developing such a condition often develops lifelong impaired lower limb mobility accompanied by hydrocephalus, and urinary and bowel incontinence. The available interventions include prenatal and postnatal surgery to fuse the dura. Prenatal surgery performed before 26 weeks of gestation reduces the risk of death or the need for ventriculoperitoneal shunting. It also enhanced results on a comprehensive index for mental and motor function. When compared to postnatal surgery, prenatal surgery reduces the manifestation of several secondary outcomes, including the degree of hindbrain herniation seen in the Chiari II malformation. Stem cell therapy for MMC on animal models of chick, ovine, and rodents with reported cases 15/63, 15, and 136, respectively, using human Embryonic Stem Cells (hESCs), Neural Stem Cells (NSCs), Mesenchymal Stem Cells (MSCs) showed significant coverage of MMC defect and slight neurogenesis was also observed. With an understanding of medical literature about in-utero regenerative capacity, it is to be appreciated that placental stem cells surgically seeded within a biocompatible scaffold of the cell patches can play a part in alleviating the spinal cord manifestation associated with MMC. Documented animal studies show that incorporating Placental Mesenchymal Stem Cells in prenatal surgery has reported improved neurogenesis and lower limb mobility. In an ovine myelomeningocele model, the development of in-utero myelomeningocele repair with human Placental Mesenchymal Stem Cells seeded onto an extracellular matrix (PMSC-ECM) enhances motor findings. The clinical trial for the first stem cell therapy on human subjects known as the “CuRe Trial: Cellular Therapy for In Utero Repair of Myelomeningocele.” is expected to be finished by 2030. So far, the cases undergoing treatment have shown significant leg movement and a greater degree of bowel and urinary control. This FDA-approved clinical trial is envisioned to be the future of treating MMC.
Feb 2024 DOI 10.14302/issn.2379-7835.ijn-24-4938
Public health interest in vaccinations and immune protection has increased with the COVID-19 pandemic. Dairy products are an important source of protein and other nutrients, and there are unresolved research questions regarding the potential health impact of dairy products on the enhancement of immune response. A systematic literature review was conducted to synthesize the published literature reporting the effects of dairy interventions on: 1) the vaccine-specific immune response and 2) immunoglobulins in the absence of vaccination. To assess study validity and quality, we used the Academy of Nutrition and Dietetics Quality Criteria Checklist. Sixty-one studies (59 clinical trials, 1 cohort, 1 cross-sectional survey) were included, spanning 1983-2017. Ten trials evaluated the effect of dairy intervention on vaccine-specific IgG, IgA, IgM, vaccine-specific antibody titers, seroprotection rates, or seroconversion rates. Of these, 7 reported significant increases with dairy interventions for post-vaccine tetanus antibodies, mean change in tetanus antibody level, total antibody titers to flagellin from Salmonella Adelaide, mean antibody titers to influenza B, influenza-specific IgA and IgG levels, and seroconversion or seroprotection rates for influenza A and B. Fifty-six studies evaluated dairy’s effects on immunoglobulins without vaccinations. The results were heterogenous, with some studies reporting significant enhancement of immunoglobulins (IgA, IgE, or IgG), while others observed no differences between groups. Clinical relevance of the immunoglobulin changes was not investigated in these studies. Dairy products and their components could enhance the efficacy of vaccines. This review highlights the evidence gaps and provides a potential roadmap for additional research.
Oct 2023 DOI 10.14302/issn.2379-7835.ijn-23-4737
Bitter melon is a popular fruit cultivated in Southeast Asia and other tropical climate regions. Bitter melon has been used in traditional medicine because of its numerous medicinal benefits, including having hypoglycemic effects. This has an indication for diabetic patients, and several clinical trials have provided evidence that orally administered bitter melon extract can reduce A1C and blood sugar levels in diabetes patients. In vitro and in vivo mechanistic studies suggest that bitter melon’s anti-diabetic actions work through intra- and extra-pancreatic mechanisms. Herein we summarize and highlight these mechanistic and clinical studies that have demonstrated the hypoglycemic effects of bitter melon in type 2 diabetes patients.
Sep 2023 DOI 10.14302/issn.2574-4496.jtc-23-4722
Background Patients with distant metastatic Medullary Thyroid Carcinoma (MTC) have an estimated 40% ten-year survival rate. Gain of function mutations in the REarranged during Transfection or RET gene in MTC can result in an aggressive phenotype resistant to traditional therapy. In this case report, we describe the treatment of an MTC patient with a unique RET kinase deletion mutation. Case presentation Since diagnosis, 21 years ago, this patient has had chronically elevated calcitonin levels (>40,000 pg/mL) that was unable to be controlled by conventual therapy and clinical trials. As result of uncontrolled MTC, metastatic disease was found in the spine, liver, and lungs. Circulating tumor DNA (ctDNA) analysis identified a RET 898-901Del mutation, reported as a variant of unknown significance. The treating physician identified that the deletion was in the activation loop of RET kinase and considered that the mutation was constitutively activating RET kinase. The patient was prescribed Pralsetinib, a small molecule inhibitor targeting the ATP binding site of RET. Pralsetinib treatment achieved a durable response and was able to significantly decrease serum calcitonin levels (<200 pg/mL) and tumor size. Conclusion This RET deletion mutation is a pathogenic mutation with comparable enzymatic activity to the more common RET M918T mutation. The case report highlights the versatility of structural biologic approaches to guide therapeutic decisions.
Jun 2022 DOI 10.14302/issn.2328-0182.japst-22-4193
The strategy for safe drug discovery and development has limited clinical success as compared to wasted time and resources annually. This is due to the fact that the results of multiphase preclinical trials are less likely to make an accurate early prediction on the safety of test compounds to progress into the clinic as a valuable therapeutic agent. A lot of time and resources has been wasted in the multistage processes of drug discovery and development that does not work at the end of the procedure every year. During pre-marketing stage, for instance, the number of unsuccessful clinical trials are greater than the successful one because of safety issues. A toxicity study at different stages of preclinical and clinical trials is a routine procedure to investigate the undesirable side effects of test compounds being manifested on the natural processes of living things. It deals with the effect and mechanism of toxicity of test compounds that triggers different biological responses on different organ systems. The biological responses that would be manifested as a result of interaction between the receptors and active molecules of a test compound could be desirable pharmacological effect or undesirable side effect or both responses are manifested simultaneously depending on the selectivity or specificity of the molecule of a test compound for its receptor subtype which makes safe drug discovery and development very challenging. The response efficiency of the body (the net outcome of the body’s biological reaction against the side effect) would determine the potency of a test compound to manifest undesirable pharmacologic effect. In other words, the amount of a drug required to cause a biological harm or injury depends on the magnitude of the body’s biological reaction in which the immune response plays a great pharmacological role by neutralizing and harmonizing xenobiotics with the biological molecules. The dose of a test compound at 100 mg/kg body weight, for instance, could be lethal to some of the study animals while it is still non-lethal to some other study animals depending on the response efficiency of the body. The immune system is well connected to each and every biological systems of the body which allows it to detect undesirable side effects being manifested through immunoglobulins signalling and activation mechanisms. This complex communication network helps to localize the diverse side effects of a test compound being manifested on different organ systems into the immune system which makes a toxicity study relatively simple to monitor. The cellular immune system becomes active following the molecule-receptor interaction and start producing antibodies which is also known as immunoglobulins to protect bodily harm and destruction. Under normal biological circumstances, the amount of immunoglobulins produced by the cellular immune system following exposure to a test compound is proportional to the number of harmful molecules interacted with its receptor subtype. Thus, with the reference to the changes in the immune response against the administered dose, it would be able to deal with the diverse undesirable side effects of a test compound being manifested on treated study animals using computational systemic biology.
Mar 2022 DOI 10.14302/issn.2692-1537.ijcv-22-4117
Several mRNA vaccines are used on the population in the U.S. I started predicting the dangers of mRNA vaccines before March 2021 and update my findings periodically. My prior model study enabled me to identify many flaws in clinical trials, side-effect evaluation methods and mechanism studies, and I also considered consistent failure in predicting drug side effects in the past and systematic failure of FDA in keeping out dangerous drugs from market. I found that the risks of vaccination cannot be determined by experiments alone and must be determined by using a combination of methods. By studying mRNA expression dynamics and kinetics, I predict that vaccination with mRNA vaccines may increase cancer risks, multiple organ failure risks, earlier death risks, genome alteration speeds by one or more mechanisms, alter the normal selection process for viral evolution resulting in more virulent viruses, and aggravate chronic diseases or cause healed diseases to relapse. Two root problems are practical inability to control expression sites and severe adverse reactions from repeated vaccination. Based on mRNA bio-distribution, the mRNA mainly strikes the liver and other vital organs, and poses grave dangers to persons whose vascular functional reserves are relatively small, or whose vascular systems are temporarily burdened by other causes such as viral infections or life activities. If an mRNA vaccine is administered on a pregnant woman by second or booster shots, spike protein synthesis in fetus brain disrupts the highly regulated protein synthesis processes, resulting in potential brain damages. In less than a year, most of my early predicted damages are being materialized or are on the track to hit the population. In this update, I present a benefits-and-risks map to show how the number of deaths caused by mRNA vaccines is grossly underestimated and why claimed benefits like 95% effectiveness rate and 90% death rate reduction are meaningless and misleading.
Feb 2022 DOI 10.14302/issn.2692-1537.ijcv-21-4053
Drug industry, controlling medical publishers and large media promote flawed medicine for their revenues by systematically laundering medical knowledge in decades. They maintain and promote flawed research models and suppress disruptive discoveries, thereby precluding reform of medicine. In this study, I will deeply explore how the wrong life model, population-based research model, misused clinical trials, flawed statistical models, the symptom based research methods, binary disease classification, failure to address the massive vital organ capacities, failure to correct biases caused by expected delay in realizing side effects, and failure to address the interference effects of non-controllable factors affect the conclusions of “effectiveness and safety” for mRNA vaccines. I will directly analyze three studies that have been relied upon by FDA in approving mNRA use authorizations: one BNT162b2 effectiveness study published in NEJM, one booster shot study published in NEJM and a Seven Integrated Health Care Organizations study published by CDC. I will expose fatal flaws in the frequency risk concept, effectiveness rate, and hazard reduction ratios, and show why 3% death rate, 95% effectiveness rate and 90% mortality reduction are all meaningless and misleading, and should never have been used as treatment guidance. I will also examine common biases that can be easily practiced by sponsors’ researchers to alter conclusions in favor of approval. By relying on laundered medical “knowledge”, FDA has consistently failed to predict latent drug side effects for any drugs and vaccines in its history. FDA approved disastrous DES in 1941, Swine Flu vaccine in 1976, and mRNA vaccines in 2020. The vaccines are used to deliver short-term benefits on a small percent of persons at the costs of damaging health, causing deaths that could be avoided, and shortening lifespans for all people in the population. I thus urge FDA to reevaluate all mRNA vaccines and revoke their use authorizations.
Feb 2022
Using samples of small cell lung tumors, a research team led by biologist Dr. Raymond discovered two new ways to induce tumor cell death. By activating ferroptosis, one of two subtypes of tumor cells can be targeted: first, iron-dependent cell death due to oxidative stress, and second, oxidative stress. Therefore, cell death can also be induced in a different way. Both types of cell death must be caused by drugs at the same time to eliminate the majority of the tumor mass. It is currently in clinical trials for cancer treatment. Auranofin, which inhibits the production of protective antioxidants in cancer cells, has been used to treat rheumatoid arthritis for decades. Future clinical trials using this combination therapy will determine the extent to which this targeted treatment option improves the prognosis of small cell lung cancer patients. It is currently in clinical trials for cancer treatment. Lung cancer is the leading cause of cancer death in the United States. Despite evidence of molecular abnormalities in biological specimens, progress in this disease is hampered by the lack of diagnostic markers useful for clinical practice. The majority of patients with lung cancer are still diagnosed at an advanced stage, when prognosis is poor. This article reviews new strategies being studied for the early detection of lung cancer. These strategies involve new methods of imaging (including low-dose computed tomography CT scanning), DNA analysis, and proteomic-based techniques. These strategies have not only improved our understanding of lung cancer but show promise in offering better survival to patients with this deadly disease. Of paramount importance in the search for methods of early detection is the need for the identification of the ideal population to screen, a multidisciplinary approach, and validation of promising techniques.
Jan 2021 DOI 10.14302/issn.2692-1537.ijcv-20-3383
With the spread of the new coronavirus around the world, governments of various countries have begun to use the mathematical modeling method to construct some virus transmission models assessing the risks of spatial spread of the new coronavirus COVID-19, while carrying out epidemic prevention work, and then calculate the inflection point for better prevention and control of epidemic transmission. This work analyzes the spread of the new coronavirus in China, Italy, Germany, Spain, and France, and explores the quantitative relationship between the growth rate of the number of new coronavirus infections and time. In investigating the dynamics of a disease such as COVID-19, its mathematical representation can be constructed at many levels of details, guided by the questions the model tries to help answer. Mathematical sophistication may have to yield to a more pragmatic approach closer to the ability to make predictions that inform public health policies. Background In December 2019 , the first Chinese patients with pneumonia of unknown cause is China admitted to hospital in Wuhan, Hubei Jinyintan , since then, COVID-19 in the rapid expansion of China Wuhan, Hubei, in a few months time, COVID-19 is Soon it spread to a total of 34 provincial-level administrative regions in China and neighboring countries, and Hubei Province immediately became the hardest hit by the new coronavirus. In an emergency situation, we strive to establish an accurate infectious disease retardation growth model to predict the development and propagation of COVID-19, and on this basis, make some short-term effective predictions. The construction of this model has Relevant departments are helpful for the prevention and monitoring of the new coronavirus, and also strive for more time for the clinical trials of Chinese researchers and the research on vaccines against the virus to eliminate the new corona virus as soon as possible. Methods According to the original data change law, Establish a Logistic growth model, we collect and compare and integrate the spread of COVID-19 in China, Italy, France, Spain and Germany, record the virus transmission trend among people in each country and the protest measures of relevant government departments. Findings Based on the analysis results of the Logistic model model, the Logistic model has a good fitting effect on the actual cumulative number of confirmed cases, which can bring a better effect to the prediction of the epidemic situation and the prevention and control of the epidemic situation. Interpretation In the early stage of the epidemic, due to inadequate anti-epidemic measures in various countries, the epidemic situation in various countries spread rapidly. However, with the gradual understanding of COVI D -19, the epidemic situation began to be gradually controlled, thereby retarding growth
Sep 2020 DOI 10.14302/issn.2692-1537.ijcv-20-3538
There were compared mechanisms infecting a human organism by different viruses in relation to interaction between human diploid cellular cycle mechanisms and coronaviruses haploid genomic mechanism. Besides there were described mechamism forming combined haploid-diploid cellular cycle of viral affected cells due to interactions between human cellular cycle mechanisms and coronaviruses genomic mechanism. Further there were considered infected way of SARS-CoV-2 from mechanism maintenance stability Internal Energy of an organism’s able-bodies cells and transmutation them into viral affected cells leading to death of affected cells of high respiratory level in nose-trachea-bronchi with transiting coronaviruses through dead cells‘ wall and infecting lungs‘ cells. Taking into account great searches of methods treatments Coronaviruses infected disease, we offered to approved through detail clinical Trial of new efficient method of treatment ill patients with SARS-CoV-2 disease which can rescue of still alive lungs‘ cells. Moreover there was reviewed offered therapy of SARS-CoV-2 induced disease.
Mar 2020 DOI 10.14302/issn.2470-5020.jnrt-20-3231
Health services research is a multidisciplinary field which involves policy makers, health care providers, as well as quality outcomes professionals of the health services provided in an organizational setting to name some. Using qualitative research methodology to get insights of both the provider and patient experience down the pipeline can help strengthen what is lacking. Bridging the gap of translation research by not just surveys 1 might be an appropriate research methodology, however, inclusion of case studies, ethnographies might help stakeholders in the field, to visualize in depth phenomenon occurring in health services research field. Telly medicine, commercial digital health status trackr might be some of the inetrventions to improvise health care services, however, knowing what are the actual needs at individual level might efficiently help in redistribution of resources or policy laws. Recruiting for clinical trials through story telling communication technology2,3, might help in recruitment for novel drug therapies to explore possibilities, however, exploring the barriers to enroll for the clinical trials, or why the drug might work effectively in some cultural population and why not on others, can only be efficiently explored through qualitative research methodologies.
Mar 2020 DOI 10.14302/issn.2766-8681.jcsr-21-3719
Background Since receiving unexplained pneumonia patients at the Jinyintan Hospital in Wuhan, China in December 2019, the new coronavirus (COVID-19) has rapidly spread in Wuhan, China and spread to the entire China and some neighboring countries. We establish the dynamics model of infectious diseases and time series model to predict the trend and short-term prediction of the transmission of COVID-19, which will be conducive to the intervention and prevention of COVID-19 by departments at all levels in mainland China and buy more time for clinical trials. Methods Based on the transmission mechanism of COVID-19 in the population and the implemented prevention and control measures, we establish the dynamic models of the six chambers, and establish the time series models based on different mathematical formulas according to the variation law of the original data. Findings The results based on time series analysis and kinetic model analysis show that the cumulative diagnosis of pneumonia of COVID-19 in mainland China can reach 36,343 after one week (February 8, 2020), and the number of basic regenerations can reach 4.01. The cumulative number of confirmed diagnoses will reach a peak of 87,701 on March 15, 2020; the number of basic regenerations in Wuhan will reach 4.3, and the cumulative number of confirmed cases in Wuhan will reach peak at 76,982 on March 20. Whether in Mainland China or Wuhan, both the infection rate and the basic regeneration number of COVID-19 continue to decline, and the results of the sensitivity analysis show that the time it takes for a suspected population to be diagnosed as a confirmed population can have a significant impact on the peak size and duration of the cumulative number of diagnoses. Increased mortality leads to additional cases of pneumonia, while increased cure rates are not sensitive to the cumulative number of confirmed cases. Interpretation Chinese governments at various levels have intervened in many ways to control the epidemic. According to the results of the model analysis, we believe that the emergency intervention measures adopted in the early stage of the epidemic, such as blocking Wuhan, restricting the flow of people in Hubei province, and increasing the support to Wuhan, had a crucial restraining effect on the original spread of the epidemic. It is a very effective prevention and treatment method to continue to increase investment in various medical resources to ensure that suspected patients can be diagnosed and treated in a timely manner. Based on the results of the sensitivity analysis, we believe that enhanced treatment of the bodies of deceased patients can be effective in ensuring that the bodies themselves and the process do not result in additional viral infections, and once the pneumonia patients with the COVID-19 are cured, the antibodies left in their bodies may prevent them from reinfection COVID-19 for a longer period of time.
Jun 2019 DOI 10.14302/issn.2576-6694.jbbs-19-2784
The aim of this clinical study was to determine the efficacy of bilateral alternating somatosensory stimulation for the management of stress and anxiety during and after the Trier Social Stress Test (TSST), a laboratory procedure for reliably inducing stress in human subjects. For this, a randomized, placebo-controlled, triple-blinded clinical trial of 80 qualified subjects was conducted. Subjects were randomized into two groups, a treatment group (n=40) and a control (placebo) group (n=40). Metrics of emotional stress assessed were a subjective rating of the level of emotional stress and salivary cortisol levels, both obtained at 3 timepoints: before treatment (baseline), immediately following completion of the TSST, and after 20 minutes of rest following completion of the TSST. Results showed that the treatment group had a statistically greater decrease in the subjective rating of stress relative to the control group both immediately following the TSST and 20 minutes after the TSST. Salivary cortisol levels in the treatment group were also lower than the control group at those same time points. These results suggest that bilateral alternating somatosensory stimulation may be effective in reducing subjective levels of stress and anxiety. It also may actively attenuate stress-related cortisol levels, which may reflect a mechanism for reducing cortisol-induced inflammation back to baseline after exposure to stressful situations.
Feb 2019 DOI 10.14302/issn.2470-5020.jnrt-19-2618
Objective Testing a new drug, treatment, and medical device clinically is critically important before prescribing it to patient. Not determining the drug’s safety and efficacy through clinical trials might impose life threatening outcomes on its consumers. The research paper describes the critical factors associated for testing any new drugs clinically, as limited research is performed in this field of public health. Study Design A qualitative systematic literature review was performed by mining relevant original peer reviewed research papers as well as some online resources like MedlinePlus due to limited availability of studies on such critical topic. Methods The databases used were Web of Sciences core collection, PubMed, Google scholar. The keywords used to search research papers were “clinical trials”, “testing new drugs”, “history of testing drugs”, “evidence-based medicine”. Conclusion Drugs which are prescribed to critical target population like pregnant women and children should be more often clinically tested if possible as majority of them are available in the market without Food and Drug Administration (FDA) approval. The abusive potential of any new drug could end up taking lives of innocent individuals. More evidence-based medicine can help translate research results on a heterogeneous population efficiently.
Aug 2018
Drug design, referred to the fields of pharmacology, biotechnology and medicine, is in silico, in vitro and in vivo assay processes of finding new candidate medications based on the biological targets. The in silicoexperiments of drug discovery are involved in the macromolecular structure databases, small molecule databases, molecular docking, de novo drug design and molecular dynamics simulations. The in vitro experiments of drug discovery need evaluate the direct interaction information between ligands and targets as well as the function of ligands on signaling pathway in the cell. The in vivo experiments of drug discovery give the convincing evidence for preclinical trial at the physiological level. In this review, we outline the drug design components of databases, virtual screening tools, biochemical assays, cell-based system and animal models.
Apr 2018
Heart failure(HF) is a disease with high morbility and mortality. The benefits of current pharmacological and device therapy for survival outcomes of patients with HF are limited. Gene therapy represents a novel promising strategy in treating HF, as it can theoretically normalize the aberrantly expressed genes and their regulatory mechanisms permanently. However, the translation of gene therapy for HF from bench to bedside has been less successful. There are many challenges ahead for gene therapy, especially in the areas of selection of the optimal targets, the needs for developing delivery systems and the improvement in design of clinical trials. In this review, we summarize the most promising gene targets which have been used in experimental and clinical studies for treating HF, highlighting the results from several clinical trials. We also review the latest development in gene therapy vectors and delivery methods, aiming to provide directions for future studies.
Apr 2018
The presence of bronchiectasis is considered an aggravating factor in COPD patients. In particular, the coexistence of bronchiectasis and COPD was associated with greater frequency and severity of exacerbations. The aim of this study is to investigate the impact of bronchiectasis in patients with COPD exacerbation. We retrospectively collected data from 212 patients admitted to the hospital with diagnosis of COPD exacerbation. In order to detect the presence of bronchiectasis, only patients that had received a chest HRCT scan examination were included in the study. We compared clinical and functional data between COPD patients with bronchiectasis and those without bronchiectasis. The prevalence of bronchiectasis was 31,6% in this study. The presence of bronchiectasis in COPD patients was associated with increased risk for isolation of PPMs in the airway (56,1% vs 28,3%, p 0,02), and in particular of Pseudomonas Aeruginosa (17,5% vs 5,6% p 0,02), and with a longer duration of hospitalization (8,22 ±3,67 vs 6,88 ± 3,43 days, p=0.004). These results could encourage efforts to optimize medical care for patients with COPD and bronchiectasis. Clinical trials with treatments for infective component are needed to investigate their impact on the reductions of exacerbations and improvements in the disease course.
Mar 2018 DOI 10.14302/issn.2642-9241.jrd-18-1958
Background Bronchoscopic lung volume reduction (BLVR) has been applied in COPD patients with heterogeneous emphysema. In this first clinical trial in Vietnam, we evaluated the safety and initial results of BLVR by one-way valve in COPD patients with severe emphysema. Methods We performed a prospective, nonrandomized, single center longitudinal study in 30 stable COPD patients with heterogeneous severe emphysema on CT-scanner, the average age of 65.17 years old, FEV1≤35 %pred., TLC ≥ 100 %pred., RV ≥ 150 %pred. and 6MWT < 450 meters. The Zephyr one-way bronchial valves (PulmonX, Redwood City, CA, USA) with the size of 5.5 mm and 4mm were placed in lobar or segmental bronchi via flexible bronchoscopy. 28 patients were placed only one valve, 1 patient with two and 1 patient with three valves. 23 valves with the size 5.5 mm diameters and 10 valves with the size 4.0mm used. All patients received optimal medical treatment at the time of procedure and during the study period. Outcomes will be assessed at 3 months after treatment include the changes of clinic, and lung function, the occurrence of complications. Results After 3 months, mean CAT scores decreased significantly compared with before procedure (17.73 ± 3.53 vs 20.10 ± 3.58) (p<0.05), with the median change of 2.73 points and the improvement more than 2 points in 76.67% of patients. 6 MWT increased at 3 months with mean 32.13 meters, 93.33% of the patients increased 6MWT, 46.67% of the patients increased 6MWT more than 26 meters. MRC decreased with the median change of 0.5 score. VC decreased by a mean 0.2 (L) (0.42 - 0.02), FEV1 increased by a mean 0.05 (L) (0.04 - 0.05) but not statistically significant (p>0.05); FVC increased by a mean 0.14 (L) (0.01 - 0.28), RV decreased by a mean 0.62 (L) (1.05 - 0.2), TLC decreased by a mean 0.52 (L) (0.77- 2.4) with statistically significant (P<0.05). The early complications were 13.33%, the later complications were 23.34% of the patients. Conclusions The unilateral bronchoscopic lung volume reduction with one-way valve (mainly one valve) in treatment of heterogeneous severe emphysema in stable COPD patients in Viet Nam have shown that this procedure is safe with encouraging initial results.
Jul 2017 DOI 10.14302/issn.2574-4372.jesr-17-1705
Drug-induced cardiotoxicity is one of the predominant reasons for drug attrition and withdrawals. This is of critical concern when potentially cardiotoxic drugs are administered to individuals with inherited arrhythmogenic cardiac diseases or with metabolic diseases such as obesity and diabetes, which are key risk factors for cardiovascular diseases. Pathophysiological alteration prevalent under such conditions can alter or exacerbate cardiotoxic responses. The growing incidence of obesity, diabetes and metabolic syndrome subject a significant percentage of the population to drug treatments, thereby augmenting their risk for drug-induced cardiovascular toxicity. Hence, screening for drug-induced cardiotoxicity early in the preclinical stages of drug development, by using appropriate human disease models, can be effective in ensuring safety in clinical trials and preventing late stage and post-marketing drug withdrawals owing to cardiotoxicity. The advent of human pluripotent stem cells (hPSC) and induced pluripotent stem cell (iPSC)-derived cardiomyocytes are revolutionizing safety/toxicity screening in human cells by providing relevant human-specific, renewable model systems to explore human drug toxicity. The ability to generate patient-specific iPSCs that can model cardiac diseases, now offers a valuable option that can further improve drug safety assessments and enable a more accurate prediction of toxicity that occurs in the representative population that are prescribed the drugs. Use of appropriate disease models will not only provide cost savings by decreasing potential drug attrition and withdrawals, seen with many drugs, but will also be a promising option to advance precision medicine
Jul 2016 DOI 10.14302/issn.2574-4372.jesr-16-1055
Human-induced pluripotent stem cells (HiPSCs) demonstrate promise in their ability to differentiate into neural cells and ultimately replace the cell types and thereby brain tissue damaged by stroke. This may diminish cognitive impairment due to stroke. Prior to transplantation, an appropriate scaffold must be determined to allow for heightened accuracy by facilitating proper adhesion, differentiation, and proliferation, increasing the likelihood of success, as will be defined in this review, in vivo. This paper aims to provide a review of available biocompatible scaffolds and their efficacy, to provide insight for future research utilizing clinical trials to study stem cell therapy as a form of post-stroke recovery. A systematic review of scaffolds outlined in full-text, peer-reviewed articles with unique experimental data, available on PubMed, will be conducted to determine an ideal scaffold, based on article and scaffold selection criteria best suited for the transplantation of human-induced pluripotent stem cells.
Mar 2016 DOI 10.14302/issn.2470-5020.jnrt-15-800
Although clinical trials in refractory epilepsy are currently carried out, the field of deep brain stimulation (DBS) in epilepsy is still at its initial stage. Little is known about where, when and how to stimulate and what would be the short and long consequences. Animal studies might provide clinicians with new ideas regarding targets for DBS. Here an overview is given regarding old and new targets in rodent models of temporal lobe epilepsy. The evidence from animal models showed that stimulation of the subiculum – either in responsive or scheduled manner - is anticonvulsant in different seizure and epilepsy models, indicating that the subiculum might be a promising candidate for DBS targets. For the rest, the antiepileptic effects of low frequency stimulation were established mostly in kindling models. The presence of a critical time window in which stimulation was effective following after discharges on kindling acquisition, demonstrates that timing of DBS is an important factor for the anticonvulsant effects of DBS.
Jan 2016 DOI 10.14302/issn.2470-5020.jnrt-15-803
We sought to identify early uses of blinding in therapeutic clinical trials of neurological disorders by multiple search methods. A 1784 report by Benjamin Franklin and others described the evaluation of the use of Mesmerism to treat neurological and other syndromes including headache and epilepsy, using blindfolds and screens. This report demonstrated the usefulness of blinding to reduce bias in clinical research, yet despite this early discovery, blinding was not widely accepted or routinely used until the 20th century. Blinded clinical trials began to be used for various neurological syndromes in the 1950s, sporadically at first and then increasing in frequency in subsequent years. The reason for this delay is unclear, but we propose several hypotheses.
Jan 2014 DOI 10.14302/issn.2324-7339.jcrhap-13-edt.1.3
This hypothesis‑driven review considers phytochemicals with putative anti‑HIV activity. It summarizes proposed mechanisms, in vitro evidence, and formulation issues, and calls for standardized assays and clinical trials to determine real‑world efficacy and safety.