Establishment of a threshold of toxicological concern for pharmaceutical intermediates based on historical repeat-dose data and its application in setting health based exposure limits.

Availability of toxicological data for pharmaceutical intermediates (IMs) used in the manufacture of small molecules is often limited. Scarcity of data - in particular, repeat-dose toxicity (RDT) - renders the calculation of health-based exposure limits (HBELs) problematic. Establishment of HBELs, including occupational exposure limits (OELs) and permitted daily exposures (PDEs) facilitating worker and patient safety respectively, is however essential.

EPIC Technique Spinal Procedure Improves Ocular Motion and Dizziness by Resolving Cranial Nerve VI Palsy.

Unlabelled: This case study demonstrates that craniocervical spinal alignment with the EPIC technique spinal procedure appears to have a potential positive impact on ocular function. This paper will report the case of a patient with cranial nerve VI palsy and dizziness, and the clinical improvements following treatment with the soundwave technology of the EPIC technique spinal procedure [1].

Objective: To report the case of a patient with cranial nerve VI (CN VI) palsy and the clinical changes that occurred after receiving treatment using the EPIC (Evolutionary Percussion Instrument Corrections) technique spinal procedure.

Addictive Behavior and Evolutionary Adaptation: Mitigated through Genetic Addiction Risk Severity Early Identification and Awareness Integration Theory.

Objectives: Humans, with their unique genetic profile, exhibit a greater propensity to develop and maintain addiction compared to other animals. This paper offers a detailed examination of addiction, co-occurring traits, and psychologic disorders, focusing on neurobiological and molecular aspects. Furthermore, the authors investigate the potential of the Awareness Integration Theoretical model as an effective therapeutic addiction treatment.

Capturing Differential Quality of Experimental Evidence in a Predictive Quantum-Mechanical Model for Respiratory Sensitization.

Asthma is of concern in occupational toxicology with significant public-health and economic costs. In the absence of benchmark in vivo and in vitro tests, the use of mechanistically sound in silico models is critical to inform hazard and to protect workers from exposure to potentially harmful substances. We recently reported on the computer-aided discovery and REdesign (CADRE) model for respiratory sensitization, which relies on a tiered structure of expert rules, molecular simulations, quantum-mechanics calculations and advanced statistics to accurately identify respiratory sensitizers from first principles.

The First Pilot Epigenetic Type Improvement of Neuropsychiatric Symptoms in a Polymorphic Dopamine D2 (-DRD2/ANKK (Taq1A)), OPRM1 (A/G), DRD3 (C/T), and MAOA (4R) Compromised Preadolescence Male with Putative PANDAS/CANS: Positive Clinical Outcome with Precision-Guided DNA Testing and Pro-Dopamine Regulation (KB220) and Antibacterial Therapies.

Pediatric autoimmune neuropsychiatric disorders associated with or without streptococcal and other bacterial infections (PANDAS/CANS) are emerging as a featured pediatric disorder. Although there is some controversy regarding treatment approaches, especially related to the behavioral sequelae, we have hypothesized in other published work that it is characterized by the rapid onset of Reward Deficiency Syndrome (RDS) in children. We propose utilizing a multi-systems biological approach involving the coupling of genetic addiction risk testing and pro-dopamine regulation (KB220/POLYGEN) to help induce "dopamine homeostasis" in patients with PANDAS, especially those with known DNA-induced hypodopaminergia.

Synergistic Epistasis and Systems Biology Approaches to Uncover a Pharmacogenomic Map Linked to Pain, Anti-Inflammatory and Immunomodulating Agents (PAIma) in a Healthy Cohort.

The global public health addiction crisis has been stark, with over 932,400 deaths in the USA and Canada from opioid overdose since 1999-2020, surpassing the mortality rates at the top of the HIV/AIDS epidemic. Both nations exhibit opioid consumption rates significantly above the norm for developed countries. Analgesic type of opioids present both therapeutic benefits and substantial health risks, necessitating balanced drug regulation, careful prescribing, and dedicated opioid stewardship.

A Complex Relationship Among the Circadian Rhythm, Reward Circuit and Substance Use Disorder (SUD).

The human brain not only controls the various physiological functions but is also the prime regulator of circadian rhythms, rewards, and behaviors. Environmental factors, professional stress, and social disintegration are regarded as the initial causative factors of addiction behavior. Shift work, artificial light exposure at night, and chronic and acute jet lag influence circadian rhythm dysfunction.

Regional Differences in Vascular Graft Degradation and Regeneration Contribute to Dilation.

Severe coronary artery disease is often treated with a coronary artery bypass graft using an autologous blood vessel. When this is not available, a commercially available synthetic graft can be used as an alternative but is associated with high failure rates and complications. Therefore, the research focus has shifted toward the development of biodegradable, regenerative vascular grafts that can convert into neoarteries.

Assessing the Impact of IL-6 and Serotonin on Pain and Symptomatology in Fibromyalgia: An Exploratory Clinical Study.

Background And Objectives: Fibromyalgia (FM) is a chronic musculoskeletal pain syndrome characterized by widespread pain and a variety of other symptoms, including fatigue, cognitive dysfunction, and sleep disturbances. Recent research has highlighted the potential role of pro-inflammatory cytokines and neurotransmitters in the pathophysiology of FM. This study aimed to investigate the relationship between serum levels of interleukin-6 (IL-6) and serotonin with the clinical parameters observed in patients with fibromyalgia.

Pilot Study of Personalized Transcranial Magnetic Stimulation with Spectral Electroencephalogram Analyses for Assessing and Treating Persons with Autism.

Autism spectrum condition (ASC) is a neurodevelopmental condition that is only partly responsive to prevailing interventions. ASC manifests core challenges in social skills, communication, and sensory function and by repetitive stereotyped behaviors, along with imbalances in the brain's excitatory (E) and inhibitory (I) signaling. Repetitive transcranial magnetic stimulation (rTMS) has shown promise in ASC and may be a useful addition to applied behavioral analysis (ABA), a gold-standard psychotherapeutic intervention.

Neuroinflammatory Approach to Surgical Trauma: Biomarkers and Mechanisms of Immune and Neuroendocrine Responses.

The severity and invasiveness of clinical outcomes from organic responses to trauma are influenced by individual, surgical, and anesthetic factors. A stress response elicits neuroendocrine and immune reactions that may lead to multi-organ dysfunction. The degree of neuroinflammatory reflex activation from trauma can increase pro-inflammatory cytokine production, leading to endothelial dysfunction, glycocalyx damage, neutrophil activation, and multisystem tissue destruction.

A historical perspective on clonidine as an alpha-2A receptor agonist in the treatment of addictive behaviors: Focus on opioid dependence.

Clonidine operates through agonism at the alpha-2A receptor, a specific subtype of the alpha-2-adrenergic receptor located predominantly in the prefrontal cortex. By inhibiting the release of norepinephrine, which is responsible for withdrawal symptoms, clonidine effectively addresses withdrawal-related conditions such as anxiety, hypertension, and tachycardia. The groundbreaking work by Gold .

Top Three Healthcare Trends in Orthopaedics Affecting Musculoskeletal Care in the Elderly.

Several trends toward patient-centered multi-care models employing translational research strategies are currently emerging in orthopaedics. These align seamlessly with epigenetics discussions in pain, a clinical approach to pain management that prioritizes tailoring healthcare to individual needs, preferences, and circumstances. Recognizing the unique genetic and epigenetic factors influencing pain perception, healthcare providers can integrate personalized insights into their patient-centered approach, offering more targeted and effective pain management strategies tailored to each individual's experience.

Randomized study of induction with bendamustine-rituximab ± bortezomib and maintenance with rituximab ± lenalidomide for MCL.

Although initial therapy of mantle cell lymphoma (MCL) is not standardized, bendamustine plus rituximab (BR) is commonly used in older patients. Rituximab (R) maintenance after induction is often used. Thus, the open-label, randomized phase 2 ECOG-ACRIN Cancer Research Group E1411 trial was designed to test 2 questions: (1) does addition of bortezomib to BR induction (BVR) and/or (2) addition of lenalidomide to rituximab (LR) maintenance improve progression-free survival (PFS) in patients with treatment-naïve MCL? From 2012 to 2016, 373 previously untreated patients, 87% aged ≥60 years, were enrolled in this trial.