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1 During the 1st day of European Congress for Integrative Medicine held September 9-11, 2016, almost the entire 1st day was scheduled for the Bi-Digital O-Ring Test, which was originally developed by this author, & consists of 2 main parts for which a U.S. patent was issued in 1993. One is a non-invasive, detection of various molecules using very strong Electromagnetic Field (EMF) Resonance Phenomenon between 2 identical molecules with identical weight. Using this strong EMF Resonance Phenomenon, most molecules & microorganisms can be detected rapidly and non-invasively without directly contacting patients. We measured the HPV-16 infection of 70 participants non-invasively in the first 30 minutes, then screened cancers for 40 volunteers who completed one page \"Mouth, Hand & Foot Writing Form,\" which took an average of 5∼10 minutes for each person to complete. Screening of 75 common cancers was made in 2-5 minutes for each patient. Analysis of 40 volunteers revealed 32 persons had some malignancies including 5 Anaplastic Astrocytomas of the L-brain, 3 Multiple Myelomas, 7 Hodgkin's Lymphomas, 8 Non-Hodgkin's Lymphomas, 2 rectum cancers (with chief complaints of worsening Irritable Bowel Syndrome). Although everyone had HPV-16 infections between about 6,000ng & 250ng, malignancy could not be found among those who had less than 1,200ng. Our individualized safe, effective and economical treatment of various cancers consists of optimal doses of Vitamin D3 with or without Taurine and/or PQQ depending on the positive synergetic compatibility among these 3 substances as normal parts of human tissue. The most serious 2 cases of rectum cancer with multiple metastasis, we confirmed very significant anti-cancer effects of their optimal doses of vitamin D3, which is increased to 800~1,000 I.U. (due to advanced cancer with multiple metastasis instead of the usual 400 I.U. for average adults). The unique 7 beneficial effects of optimal dose of Vitamin D3 (also Taurine or PQQ) include: 1) significant Anti-cancer effects without side effects; 2) marked decrease in DNA mutation as decreases in 8-OH-dG; 3) marked urinary excretion of Viruses, Bacteria, Fungi, & Toxic substances, including Asbestos & metals; 4) marked increase in Acetylcholine in the brain & the rest of the body; 5) marked increase in DHEA; 6) marked decrease in β-Amyloid (I-42); 7) marked decrease in Cardiac Troponin I. Optimal dose of Vitamin D3 is clinically most important for cancer, ischemic heart, and memory problems. Optimal dose of Taurine is 150∼175mg and PQQ is 5-7.5mg and should be taken 3-4 times a day, depending on the patient. Medications and supplements including excessive Vitamin C (as well as multivitamins) but also inhibited optimal doses of Vitamin D3, Taurine & PQQ. Often coffee, drinks containing high Vitamin C content (e.g., some green tea & orange juice), & multivitamins as well as pain medicine (e.g., Oxycodone), strong EMF from cellular phones, and strong negative BDORT underwear often completely eliminate the above beneficial effects of Vitamin D3 and promote growth of cancer.

This exploratory study compared doses of ferucarbotran, a superparamagnetic iron oxide nanoparticle, in sentinel lymph nodes (SLNs) and quantified the SLN iron load by dose and localization. Eighteen females aged ≥20 years scheduled for an SLN biopsy with node-negative breast cancer were divided into two equal groups and administered either 1 mL or 0.5 mL ferucarbotran. Iron content was evaluated with a handheld magnetometer and quantification device. The average iron content was 42.8 µg (range, 1.3–95.0; 0.15% of the injected dose) and 21.9 µg (1.1–71.0; 0.16%) in the 1-mL and 0.5-mL groups, respectively (p = 0.131). The iron content of the closest SLN compared to the second SLN was 53.0 vs. 10.0 µg (19% of the injected dose) and 34.8 vs. 4.1 µg (11.1%) for the 1-mL and 0.5-mL groups, respectively (p = 0.001 for both). The magnetic field was high in both groups (average 7.30 µT and 6.00 µT in the 1-mL and 0.5-mL groups, respectively) but was not statistically significant (p = 0.918). The magnetic field and iron content were correlated (overall SLNs, p = 0.02; 1-mL, p = 0.014; 0.5-mL, p = 0.010). A 0.5-mL dose was sufficient for SLN identification. Primary and secondary SLNs could be differentiated based on iron content. Handheld magnetometers could be used to assess the SLN iron content.

While a visiting Professor at the University of Paris, VI (formerly Sorvonne) more than 40 years ago, the Author became very good friends with Dr. Paul Nogier who periodically gave seminars and workshops in Paris. After the author diagnosed his cervical problem & offered him simple help, Dr. Nogier asked the Author to present lectures and demonstrations on the effects of ear stimulation, namely the effects of acupuncture & electrical stimulation of the ear lobules. It is only now, in 2019 that we have discovered 2-5 minute high frequency stimulation of the ear lobule inhibits cancer activity for 1- 4 hours post stimulation. Although the procedure is extremely simple. First take optimal dose of Vitamin D3, which has the most essential 10 unique beneficial factors required for every human cell activity. Next, apply high frequency stimulation to ear lobule while the worst ear lobule is held by all fingers with vibrator directly touching the surface of the worst ear lobule, preferably after patient repeatedly takes optimal dose of Vitamin D3. When the worst ear lobule is held between thumb & index fingers and applying mechanical stimulation of 250 ~ 500 mechanical vibration/second for 2 ~ 5 minutes using an electrical vibrator, there is rapid disappearance of cancer activity in both the brain and rest of the body for short time duration 1 ~ 4 hours. The effect often increases by additional pressure by holding fingers. As of May 2019, the Author found that many people from various regions of the world developed early stages of multiple cancers. For evaluation of this study, U. S. patented Bi-Digital O-Ring Test (BDORT) was used which was developed by the Author while doing his Graduate experimental physics research at Colombia University. BDORT was found to be most essential for determining the beneficial effects as well as harmful effects of any substance or treatment. Using BDORT, Author was the first to recognize severe increasing mid-backache was an early sign of pancreatic cancer of President of New York State Board of Medicine after top pain specialists failed to detect the cause after 3 years of effort, while the BDORT showed early stages of cancer whereas conventional X-Ray of the pancreas did not show any cancer image until 2 months after Author detected with BDORT. For example, the optimal dose of the banana is usually about 2.0 - 2.5 millimeters cross section of the banana. A whole banana is more than 50 ~ 100 times the optimal dose. Any substance eaten in more than 25 times of its optimal dose becomes highly toxic and creates DNA mutations which can cause multiple malignancies in the presence of strong electro-magnetic field. With standard medication given by doctor, patients often become sick and they are unable to reduce body weight, unless medication is reduced or completely stopped. When the amount of zinc is very high, DNA often becomes unstable and multiple cancers can grow rapidly in the presence of strong electromagnetic field. Large amount of Vitamin C from regular orange or orange juice inhibit the most important Vitamin D3 effects. At least 3 kinds of low Vitamin C oranges will not inhibit Vitamin D3. Since B12 particularly methyl cobalamin which is a red small tablet is known to improve brain circulation very significantly we examined its effect within 20 seconds of oral intake we found the following very significant changes. Acetylcholine in both sides of the brain often increases over 4,500 ng. Longevity gene Sirtuin 1 level increases significantly for short time of few hours. Thymosin α1 and Thymosinβ4 both increase to over 1500 ng from 20 ng or less.

Previous study indicated Human Papilloma Virus-Type 16 (HPV-16) has important role in genesis of ovarian cancer, uterus cancer, & breast cancer. Omura, Y. noticed HPV-16 virus co-exists with single-cell parasite Toxoplasma Gondii (T.G.) infection in most of the cancer tissues he examined. Therefore, he thought some unknown virus must exist in the T.G. In early 2018, he found there is strong Human Herpes Virus-Type 8 (HHV-8) infection in every cell of Toxoplasma Gondii he examined. Thus, we found in every cancer cells there are co-existing cancer-promoting factors of HPV-16 & HHV-8 infection associated with Toxoplasma Gondii. As a common source of these infections in human cancer patients, we found most egg yolk has co-existing HPV-16, HHV-8 & Toxoplasma Gondii, but egg whites are free of these infections & can be eaten safely as protein supply. Many cats and dogs also have these infections. As most important, safe treatment of cancer, we found repeated optimal dose of Vitamin D3 with optimal interval of about 8 hours is ideal because of 10 unique, beneficial effects discovered by him. Individually determined one optimal dose of Vitamin D3 has most effective anti-cancer effects in hopeless, advanced, cancer patients by reducing extremely high Integrin α5β1 of over 1500ng to normal value of 0.002∼0.004ng and 8-OH-dG (proportional to DNA mutation which is required for cancer growth) of over 60∼80ng to normal value of 0.1∼0.25ng for average 8 hours and 6000∼9000ng of strong pathogenic infection of HPV-16 & HHV-8 in cancer tissue reduced to safe range of less than 500ng by markedly increased urinary excretion. Concerning beneficial effect of optimal dose of Vitamin D3, all the previous studies failed to use individualized optimal dose. As a result, they could not properly evaluate beneficial effects & side effects and many reports claimed there were no significant beneficial effects including anti-cancer effects. Although optimal dose of Vitamin D3 can eliminate these viral infections very significantly but not less than 500∼300ng. Cancer incidence is only significant when these viruses are above 6000ng inside the body. Thus, we can keep potentially serious patients with strong cancer-contributing virus infections at relatively safe low degree of infection of much less than 3000ng. Our ideal treatment for advanced cancer patients is a combination of 1) Individually determined Optimal dose of Vitamin D3 with optimal interval of about 8 hours, 2) Selective Drug Uptake Enhancement Method by manual stimulation organ representation area of pathological organs at hands, 3) Stimulation of Thymus gland representation area of the back of the hand which was discovered by Omura, Y. in 2017, & 4) Identification & removal of multiple co-existing cancer-promoting factors. This combination of 4 new methods of treatment was found to be most effective & safe treatment for not only hopelessly advanced cancer patients but also many other difficult medical problems.

A completely healthy middle-aged female High School teacher developed stomach cancer 1 month after she spent several hours talking face to face with one person with serious stomach problem. Two months later she had surgical removal of stomach cancer. Our research confirmed that in the presence of coexisting strong virus infection of HPV-16 & HHV-6 and strong Electromagnetic field, early stage of cancer can develop very rapidly within 24 hours and these rapidly developed cancers are infectious & difficult to treat. Just before Thanksgiving Day (late November) the 1st author drank one full cup of Eggnog, at the same time he also ate part of Blueberry Pie. About 6 hours later the 1st author developed severe left low abdominal pain and diarrhea. Since he realized eggnog had extremely strong infection of HPV-16 and HHV-8 surrounded by strong electromagnetic field this might have caused early stage cancer and found the presence of early stages of 5 new cancers: 1) Hepatoma of liver 2) Hodgkin's lymphoma 3) Transitional Cell Carcinoma of Urinary Bladder 4) Adenocarcinoma of Pancreas 5) Adenocarcinoma of the Breast. All of these cancers did not exist before this unplanned accidental human experiment. In 2017 Pancreatic cancer and Breast cancer were found in the 1st author within 24 hours after 4 hours of medical examination of middle aged Japanese male patient with chief complaints of Breast Cancer & Pancreatic Cancer in close distance. The patient also had strong infection of these viruses. The author was able to eliminate these 2 cancers completely a few months before drinking the eggnog. The other cancers were also developed under similar circumstances all of them were eventually eliminated, but all these 5 cancers did not exist before drinking eggnog. The eggnog had a very high concentration of about 10000ng of HPV-16 and HHV-8 and most of cancer tissue has over maximum infection of both viruses, 7000-11000ng. The reason we have been using optimal dose of Vitamin D3 every 8 hours for every cancer patient is we can continuously excrete cancer contributing viruses to much less than 6000ng since when viruses of HPV-16 & HHV-8 are less than 6000ng, the cancer was less active. We could not eliminate the 5 infectious cancers in the first author in spite of our improved treatment with combine use of optimal doses of vitamins D3 & white fleshed Dragon fruits (since we found it to contain near optimal doses of DHEA, Zinc, Magnesium, Lithium, and a small amount of Vitamin D3, etc.) Fortunately, on Dec. 8, 2018, for the first time in cancer treatment we succeeded in completely eliminating active cancer semi-permanently under specific conditions. In this study the second time author was able to semi-permanently inhibit all 3 cancers' activity. Through this process, we were able to detect the presence or absence of active cancer very accurately from 2-10 cc of urine or rapidly changing QRS complex of ECGs. In the subsequent 10 days no cancers were detected once Thymosin α1 and 3 Thymosin β4 reach very high value of 800ng measured using reference control substances.

Abstract Linezolid has been successfully used for treatment of multidrug-resistant tuberculosis (MDR-TB). However, dose- and duration-related toxicity limit its use. Here, our aim was to search relevant pharmacokinetics (PK)/pharmacodynamics (PD) literature to identify the effective PK/PD index and to define the optimal daily dose and dosing frequency of linezolid in MDR-TB regimens. The systematic search resulted in 8 studies that met inclusion criteria. A significant PK variability was observed. Efficacy of linezolid seems to be driven by area under the concentration-time curve (AUC)/minimum inhibitory concentration (MIC). Literature is inconclusive about the preferred administration of a daily dose of 600 mg. To prevent development of drug resistance, an AUC/MIC ratio of 100 in the presence of a companion drug at relevant exposure is required. A daily dose of 600 mg seems appropriate to balance between efficacy and toxicity. Being a drug with a very narrow therapeutic window, linezolid treatment may benefit from a more personalized approach, that is, measuring actual MIC values and therapeutic drug monitoring.

There has been increasing attention to dose optimization in the development of targeted oncology therapeutics. The current report has analyzed the dose selection approaches for 116 new molecular entities (NMEs) approved for oncology indications by the US FDA from 2010 to August 2021, with the goal to extract learnings about the ways to select the optimal dose. The analysis showed that: (1) the initial label dose was lower than the maximum tolerated dose (MTD) or maximum studied dose (MSD) in Phase 1 for the majority of approved NMEs, and that the MTD approach is no longer the mainstay for dose selection; (2) there was no dose ranging or optimization beyond Phase 1 dose escalation for ~ 80% of the NMEs; (3) integrated dose/exposure–response analyses were commonly used to justify the dose selection; (4) lack of dose optimization led to dose-related PMRs/PMCs in 14% of cases, but 82% of these did not result in change of the initial label dose; and (5) depending on properties of the NME and specific benefit/risk considerations for the target patient population, there could be different dose selection paradigms leading to identification of the appropriate clinical dose. The analysis supports the need to incorporate more robust dose optimization during oncology clinical development, through comparative assessment of benefit/risk of multiple dose levels, over a wide exposure range using therapeutically relevant endpoints and adequate sample size. On the other hand, in certain cases, data from FIP dose escalation may be adequate to support the dose selection.

Abstract Background Amikacin has been used for over 40 years in multidrug resistant tuberculosis (MDR-TB), but there is still debate on the right dose. The aim of this review was to search relevant pharmacokinetic (PK) and pharmacodynamic (PD) literature for the optimal dose and dosing frequency of amikacin in MDR-TB regimens trying to optimize efficacy while minimizing toxicity. Methods A systematic review on the value of amikacin as second-line drug in the treatment of MDR-TB was performed. Results Five articles were identified with data on PK, hollow-fiber system model for TB and or early bactericidal activity of amikacin. Despite the long period in which amikacin has been available for the treatment of MDR-TB, very little PK data is available. This highlights the need for more research. Conclusions Maximum concentration (Cmax) of amikacin related to MIC proved to be the most important PK/PD index for efficacy. The target Cmax/MIC ratio should be 10 at site of infection. Cumulative area under the concentration-time curve (AUC) corresponding with cumulative days of treatment was associated with an increased risk of toxicity.

Abstract Background Linezolid exhibits remarkable sterilizing effect in tuberculosis; however, a large proportion of patients develop serious adverse events. The congener tedizolid could have a better side-effect profile, but its sterilizing effect potential is unknown. Methods We performed a 42-day tedizolid exposure-effect and dose-fractionation study in the hollow fiber system model of tuberculosis for sterilizing effect, using human-like intrapulmonary pharmacokinetics. Bacterial burden was examined using time to positivity (TTP) and colony-forming units (CFUs). Exposure-effect was examined using the inhibitory sigmoid maximal kill model. The exposure mediating 80% of maximal kill (EC80) was defined as the target exposure, and the lowest dose to achieve EC80 was identified in 10000-patient Monte Carlo experiments. The dose was also examined for probability of attaining concentrations associated with mitochondrial enzyme inhibition. Results At maximal effect, tedizolid monotherapy totally eliminated 7.1 log10 CFU/mL Mycobacterium tuberculosis over 42 days; however, TTP still demonstrated some growth. Once-weekly tedizolid regimens killed as effectively as daily regimens, with an EC80 free drug 0- to 24-hour area under the concentration-time curve-to-minimum inhibitory concentration (MIC) ratio of 200. An oral tedizolid of 200 mg/day achieved the EC80 in 92% of 10000 patients. The susceptibility breakpoint was an MIC of 0.5 mg/L. The 200 mg/day dose did not achieve concentrations associated with mitochondrial enzyme inhibition. Conclusions Tedizolid exhibits dramatic sterilizing effect and should be examined for pulmonary tuberculosis. A tedizolid dose of 200 mg/day or 700 mg twice a week is recommended for testing in patients; the intermittent tedizolid dosing schedule could be much safer than daily linezolid.

The growing demand for healthcare and population increase have accelerated the pharmaceutical industry, resulting in large-scale drug production processes. Consequently, partially or fully treated effluents are often released into the environment, posing risks to both ecosystems and human health. Pharmaceutical wastewater, particularly antibiotics, significantly contaminates aquatic habitats. This study investigated the use of plant-based natural coagulants (NC) as a low-cost, sustainable, and eco-friendly alternative to synthetic chemicals for the treatment of industrial pharmaceutical wastewater. Among the various natural coagulants, Moringa oleifera (moringa leaves) and Mangifera indica (mango leaves) were selected for this study. Jar test experiments were performed by mixing a 3 mL stock solution of each coagulant with 1000 mL of pharmaceutical wastewater in a beaker. The treatment was conducted under varying hydraulic retention times (HRT) of 2, 4, 6, and 8 h using 150 µm coagulant powders. Parameters such as pH, turbidity, TS, total dissolved solids (TDS), total suspended solids (TSS), chemical oxygen demand (COD), alkalinity, phenolic compounds, and phosphate were analyzed. The results indicated that moringa leaf powder achieved the highest COD reduction of approximately 86% at an 8 h HRT. Furthermore, the treated coagulant residues were analyzed using FE-SEM and EDX to evaluate surface morphology and elemental composition before and after wastewater treatment.