Indian food habit & food ingredients may have a role in lowering the severity & high death rate from COVID-19 in Indians: findings from the first nutrigenomic analysis.

Background & objectives: During the COVID-19 pandemic, the death rate was reportedly 5-8 fold lower in India which is densely populated as compared to less populated western countries. The aim of this study was to investigate whether dietary habits were associated with the variations in COVID-19 severity and deaths between western and Indian population at the nutrigenomics level. Methods: In this study nutrigenomics approach was applied. Blood transcriptome of severe COVID-19 patients from three western countries (showing high fatality) and two datasets from Indian patients were used. Gene set enrichment analyses were performed for pathways, metabolites, nutrients, etc., and compared for western and Indian samples to identify the food- and nutrient-related factors, which may be associated with COVID-19 severity. Data on the daily consumption of twelve key food components across four countries were collected and a correlation between nutrigenomics analyses and per capita daily dietary intake was investigated. Results: Distinct dietary habits of Indians were observed, which may be associated with low death rate from COVID-19. Increased consumption of red meat, dairy products and processed foods by western populations may increase the severity and death rate by activating cytokine storm-related pathways, intussusceptive angiogenesis, hypercapnia and enhancing blood glucose levels due to high contents of sphingolipids, palmitic acid and byproducts such as CO2 and lipopolysaccharide (LPS). Palmitic acid also induces ACE2 expression and increases the infection rate. Coffee and alcohol that are highly consumed in western countries may increase the severity and death rates from COVID-19 by deregulating blood iron, zinc and triglyceride levels. The components of Indian diets maintain high iron and zinc concentrations in blood and rich fibre in their foods may prevent CO2 and LPS-mediated COVID-19 severity. Regular consumption of tea by Indians maintains high high-density lipoprotein (HDL) and low triglyceride in blood as catechins in tea act as natural atorvastatin. Importantly, regular consumption of turmeric in daily food by Indians maintains strong immunity and curcumin in turmeric may prevent pathways and mechanisms associated with SARS-CoV-2 infection and COVID-19 severity and lowered the death rate. Interpretation & conclusions: Our results suggest that Indian food components suppress cytokine storm and various other severity related pathways of COVID-19 and may have a role in lowering severity and death rates from COVID-19 in India as compared to western populations. However, large multi-centered case-control studies are required to support our current findings.

Positive Clinical Outcomes for Severe Reported Pain Using Robust Non-Addictive Home Electrotherapy-A Case-Series.

The North American opioid epidemic has resulted in over 800,000 related premature overdose fatalities since 2000, with the United States leading the world in highest opioid deaths per capita. Despite increased federal funding in recent years, intended to address this crisis, opioid overdose mortality has continued to increase. Legally prescribed opioids also chronically induce a problematic reduction in affect. While an ideal analgesic has yet to be developed, some effective multimodal non-opioid pharmacological regimens for acute pain management are being more widely utilized. Some investigators have suggested that a safer and more scientifically sound approach might be to induce "dopamine homeostasis" through non-pharmacological approaches, since opioid use even for acute pain of short duration is now being strongly questioned. There is also increasing evidence suggesting that some more robust forms of electrotherapy could be applied as an effective adjunct to avoid the problems associated with opioids. This 4-patient case-series presents such an approach to treatment of severe pain. All 4 of these chiropractic treatment cases involved a component of knee osteoarthritis, in addition to other reported areas of pain. Each patient engaged in a home recovery strategy using H-Wave® device stimulation (HWDS) to address residual extremity issues following treatment of spinal subluxation and other standard treatments. A simple statistical analysis was conducted to determine the change in pain scores (Visual Analogue Scale) of pre and post electrotherapy treatments, resulting in significant reductions in self-reported pain (p-value = 0.0002). Three of the four patients continued using the home therapy device long-term as determined by a post-analysis questionnaire. This small case-series demonstrated notably positive outcomes, suggesting consideration of home use of HWDS for safe, non-pharmacological and non-addictive treatment of severe pain.

Evaluation of Probiotic Properties of Novel Brazilian Lactiplantibacillus plantarum Strains.

Beneficial effects of Lactiplantibacillus plantarum strains have been widely reported. Knowing that the effects of probiotic bacteria are strain-dependent, this study aimed to characterize the probiotic properties and investigate the gastrointestinal protective effects of nine novel L. plantarum strains isolated from Bahia, Brazil. The probiotic functionality was first evaluated in vitro by characterizing bile salt and acidic tolerance, antibacterial activity, and adhesion to Caco-2 cells. Antibiotic resistance profile, mucin degradation, and hemolytic activity assays were also performed to evaluate safety features. In vivo analyses were conducted to investigate the anti-inflammatory effects of the strains on a mouse model of 5-Fluorouracil-induced mucositis. Our results suggest that the used L. plantarum strains have good tolerance to bile salts and low pH and can inhibit commonly gastrointestinal pathogens. Lp2 and Lpl1 strains also exhibited high adhesion rates to Caco-2 cells (13.64 and 9.05%, respectively). Phenotypical resistance to aminoglycosides, vancomycin, and tetracycline was observed for most strains. No strain showed hemolytic or mucolytic activity. Seven strains had a protective effect against histopathological and inflammatory damage induced by 5-FU. Gene expression analysis of inflammatory markers showed that five strains upregulated interleukin 10 (Il10), while four downregulated both interleukin 6 (Il6) and interleukin 1b (Il1b). Additionally, all strains reduced eosinophilic and neutrophilic infiltration; however, they could not prevent weight loss or reduced liquid/ food intake. Altogether, our study suggests these Brazilian L. plantarum strains present good probiotic characteristics and safety levels for future applications and can be therapeutically adjuvant alternatives to prevent/treat intestinal mucositis.

Neurobiology and Spirituality in Addiction Recovery.

This commentary explores the neurobiology of spirituality and asks whether it is possible or desirable to apply genetic engineering to increase human spiritual and religious experience - (gene-spirituality) to deal better with the ever-increasing catastrophes that face humanity? Neurological connections between spirituality and reward genes, reward deficiencies (RDS) (hypodopaminergia), the mirror neuron system, and the default mode network are examined. Some interventions from addiction medicine that may be useful to enhance the neuro-spirituality connectome identified as a cornerstone of the Purpose and Meaning of Life as Reward (PMLR) are identified as reasonable targets for interventions to treat RDS and balance DMN activity.

Bacteriocins as an alternative in the treatment of infections by Staphylococcus aureus.

Staphylococcus aureus (S. aureus) is a highly versatile Gram-positive bacterium that is carried asymptomatically by up to 30% of healthy people, while being a major cause of healthcare-associated infections, making it a worldwide problem in clinical medicine. The adaptive evolution of S. aureus strains is demonstrated by its remarkable capacity to promptly develop high resistance to multiple antibiotics, thus limiting treatment choice. Nowadays, there is a continuous demand for an alternative to the use of antibiotics for S. aureus infections and a strategy to control the spread or to kill phylogenetically related strains. In this scenario, bacteriocins fit as with a promising and interesting alternative. These molecules are produced by a range of bacteria, defined as ribosomally synthesized peptides with bacteriostatic or bactericidal activity against a wide range of pathogens. This work reviews ascertained the main antibiotic-resistance mechanisms of S. aureus strains and the current, informative content concerning the applicability of the use of bacteriocins overlapping the use of conventional antibiotics in the context of S. aureus infections. Besides, we highlight the possible application of these biomolecules on an industrial scale in future work.

Quantitative Electroencephalography Analysis (qEEG) of Neuro-Electro-Adaptive Therapy 12™ [NEAT12] Up-Regulates Cortical Potentials in an Alcoholic during Protracted Abstinence: Putative Anti-Craving Implications.

INTRODUCTION: Cranial electrotherapy stimulation (CES) is a noninvasive therapy that has been used for decades in the United States to treat anxiety, depression, and insomnia in the general population. The effectiveness of CES has been questioned by many and its use is considered controversial. In this study we are presenting data on one alcoholic patient using a newly engineered device we call Neuro-Electro-Adaptive Therapy 12™ [NEAT12]. This hybrid device utilizes TENS current characteristics yielding CES effects. This device has been found to primarily target the excitation of the Cingulate Gyrus region of the brain. CASE PRESENTATION: This is a 42 year old male who has been abstinent from alcohol for approximately two months. The data presented herein represents the pre to post qEEG differences of an alcoholic in protracted abstinence. This subject was evaluated both before and after using the NEAT-12 device. The pre to post comparisons suggest that the cortical potentials especially at the Cingulate Gyrus are up regulated after using the device. The absolute power changes obtained shows a decrease of more than 2 SD as noted in the delta wave spectrum. Also noted is an overall cortical increase in the alpha spectrum. The resting alert state of a neuro typical population is most prominently marked by a regulation of 7.5-11 Hz alpha throughout the cortex. The decreased in delta and theta suggests an up regulation of the prefrontal cortex and the anterior Cingulate Gyrus a site involved in substance use disorder (SUD). CONCLUSION: A presence of dominant slow waves through the prefrontal cortex and the anterior Cingulate Gyrus is often associated with OCD, anxiety, impulsivity and cravings in addicted populations. It is conceivable that our initial finding of altered electrical activity of the brain using qEEG analysis suggests the NEAT-12 may induce a "normalization" of aberrant electrical activity of the cortical region of the brain known to occur during protracted abstinence of alcoholics. It may have utility as a putative anti-craving CES device and therefore warrants intensive investigation.

Coupling Genetic Addiction Risk Score (GARS) with Electrotherapy: Fighting Iatrogenic Opioid Dependence.

The endemic of legal opioid iatrogenic induced prescription drug abuse is of major world-wide concern. Understanding pain pathways and the role of dopaminergic tone in the neurophysiology of pain relief provides potential therapeutic solutions. A 2011 NIDA report indicated that approximately 8.7% of the entire US population above the age of 12 years has used a psychoactive drug within the past 30 days. It has been reported that the overall genetic contribution to the variance of Substance Use Disorder (SUD) was approximately 60% but each candidate gene evaluated by GWAS was relatively small. In an attempt to combat this global endemic we are proposing a number of alternative strategies. Prevention of death due to opioid overdose and attenuation of prescription abuse should focus on strategies that target 1) high-dosage medical users; 2) persons who seek care from multiple doctors; 3) persons involved in "drug diversion"; 4) genetic testing for addiction liability and severity indices; 5) non-pharmacolgical analgesic treatments such as electrotherapy.

Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS): Clinical Ramifications as a Function of Molecular Neurobiological Mechanisms.

In accord with the new definition of addiction published by American Society of Addiction Medicine (ASAM) it is well-known that individuals who present to a treatment center involved in chemical dependency or other documented reward dependence behaviors have impaired brain reward circuitry. They have hypodopaminergic function due to genetic and/or environmental negative pressures upon the reward neuro-circuitry. This impairment leads to aberrant craving behavior and other behaviors such as Substance Use Disorder (SUD). Neurogenetic research in both animal and humans revealed that there is a well-defined cascade in the reward site of the brain that leads to normal dopamine release. This cascade has been termed the "Brain Reward Cascade" (BRC). Any impairment due to either genetics or environmental influences on this cascade will result in a reduced amount of dopamine release in the brain reward site. Manipulation of the BRC has been successfully achieved with neuro-nutrient therapy utilizing nutrigenomic principles. After over four decades of development, neuro-nutrient therapy has provided important clinical benefits when appropriately utilized. This is a review, with some illustrative case histories from a number of addiction professionals, of certain molecular neurobiological mechanisms which if ignored may lead to clinical complications.

Biomarkers, critical disease pathways, drug targets, and alternative medicine in male breast cancer.

While breast cancer (BC) is commonest malignancy among female with highest death rate, male breast cancer (MBC) is very rare but exhibits highest cancer specific death in men and the incidences of MBCs are rising rapidly. Due to rarity of the disease, no detail information about biomarkers and drug targets available and because of late diagnosis and rarely understood the pathogenesis at molecular level, the treatment of MBC is also not yet standardized. Though the MBC biology, pathogenesis, and the clinical outcomes resembles with female breast cancer (FBC), they are quite unique in many aspects. Therefore, the uses of FBC specific drugs for treatment of MBC are not only dissatisfactory but also increases mortality rate due to severe side effects of these conventional drugs. To avoid side effects of usual therapeutic drugs, new drugs and their targets should be identified and evaluated, where the dietary phytochemicals may be the alternative of currently used drugs. Similarly, an integrated strategy and pharmacogenomics approach is now essential to fight against this malady. This article will deal with different aspects of MBC including biomarkers, pathways, drug targets, and common dietary phytochemicals as effective alternatives of conventional chemotherapeutic drugs for targeted therapy without any side effect.