Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats.

These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route. Toxicokinetic estimation revealed a dose-proportional increase in plasma exposure to diclofenac. The formulation was well tolerated in males; however, mortality was observed in females (2/15) at the highest dose (15 mg/kg/day). Adverse gastrointestinal events related to NSAIDS and a few other treatment-related effects on clinical and anatomic pathology were noted at the 15 mg/kg/day dose, which normalized at the end of the 2-week recovery period. In addition, the excipient povidone K12 was present in a higher amount than the approved Inactive Ingredient Database (IID) limit in the proposed novel formulation. It was qualified through a separate 28-day repeated dose toxicity study by intravenous route in Wistar rats. Povidone K12 was found to be well tolerated and safe up to a dose of 165 mg/kg/day. No treatment-related adverse effects were observed in this study. In conclusion, repeated administration of a novel intravenous formulation containing diclofenac sodium was found to be safe up to the dose of 7 mg/kg/day in female rats and 15 mg/kg/day in male rats.

A Retrospective Comparison of Electrocardiographic Parameters in Ketamine and Tiletamine-Zolazepam Anesthetized Indian Rhesus Monkeys (Macaca mulatta).

Electrocardiographic evaluation is performed in rhesus monkeys to establish the cardiovascular safety of candidate molecules before progressing to clinical trials. These animals are usually immobilized chemically by ketamine (KTM) and tiletamine-zolazepam (TZ) to obtain a steady-state heart rate and to ensure adequate human safety. The present study aimed to evaluate the effect of these anesthetic regimens on different electrocardiographic parameters. Statistically significant lower HR and higher P-wave duration, RR, QRS, and QT intervals were observed in the KTM-anesthetized group in comparison to TZ-anesthetized animals. No significant changes were noticed in the PR interval and p-wave amplitude. Sex-based significance amongst these parameters was observed in male and female animals of TZ- and KTM-anesthetized groups. Regression analysis of four QTc formulas in TZ-anesthetized rhesus monkeys revealed that QTcNAK (Nakayama) better corrected the QT interval than QTcHAS (Hassimoto), QTcBZT (Bazett), and QTcFRD (Fridericia) formulas. QTcNAK exhibited the least correlation with the RR interval (slope closest to zero and r = .01) and displayed no statistical significance between male and female animals. These data will prove useful in the selection of anesthetic regimens for chemical restraint of rhesus monkeys in nonclinical safety evaluation studies.

Design, synthesis and biological evaluation of novel pyrazolo-pyrimidin-amines as potent and selective BTK inhibitors.

To discover the best-in-class Bruton's Tyrosine Kinase (BTK) inhibitors, for th treatment of autoimmune disorders like cancer (B-Cell Lymphoma (BCL)) and rheumatoid arthritis (RA), in the present investigation, novel structural optimizations were carried out. Introduction of novel bicyclic amine linkers and aromatic backbone led to series of compounds 9a-h and 14a-u. Compound 14b was found to be potent, orally bioavailable, selective and irreversible BTK inhibitor. In vitro, 14b showed IC50 of 1.0 nM and 0.8 nM, in BTK and TMD8 assays, respectively. In vivo,14b displayed robust efficacy in collagen-induced arthritis (CIA) and TMD8 xenograft models, which could be correlated with its improved oral bioavailability. In the repeated dose acute toxicity study, 14b showed no adverse changes, indicating that the BTK inhibitor 14b could be viable therapeutic option for the treatment of autoimmune disorders.

Comparison of different QT correction methods for nonclinical safety assessment in ketamine-anesthetized Indian rhesus monkeys (Macaca mulatta).

Rhesus monkeys are a non-rodent species employed in the preclinical safety evaluation of pharmaceuticals and biologics. These nonhuman primate species have been increasingly used in biomedical research because of the similarity in their ionic mechanisms of repolarization with humans. Heart rate and QT interval are two primary endpoints in determining the pro-arrhythmic risk of drugs. As heart rate and QT interval have an inverse relationship, any change in heart rate causes a subsequent change in QT interval. This warrants for calculation of a corrected QT interval. This study aimed to identify an appropriate formula that best corrected QT for change in heart rate. We employed seven formulas based on source-species type, clinical relevance, and requirements of various international regulatory guidelines. Data showed that corrected QT interval values varied drastically for different correction formulas. Equations were compared on their slope values based on QTc versus RR plots. The rank order of the slope for different formulas was (closest to farthest from zero) QTcNAK, QTcHAS, QTcBZT, QTcFRD, QTcVDW, QTcHDG, and QTcFRM. QTcNAK emerged to be the best correcting formula in this study. It showed the least correlation with the RR interval (r = -0.01) and displayed no significant difference amongst the sexes. As there is no universally recognized formula for preclinical use, the authors recommend developing a best-case scenario model for specific study designs and individual organizations. The data from this research will be helpful in deciding an appropriate QT correction formula for the safety assessment of new pharmaceuticals and biologics.

Spatiotemporal evaluation of drought characteristics based on standard drought indices at various timescales over Uttar Pradesh, India.

Prolonged and repeated drought, as seen in India and other parts of South Asia, is a symptom of climate change, which is partially the result of human interventions. The performance of the widely used drought metrics Standardized Precipitation Index (SPI) and Standardized Precipitation Evapotranspiration Index (SPEI) are evaluated for 18 stations in Uttar Pradesh state for the period 1971 to 2018 in this study. Drought characteristics such as intensity, duration, and frequency of different categories are estimated and compared based on SPI and SPEI. In addition, station proportion is estimated at a different timescales, providing a better insight into temporal variability drought of a specific category. Spatiotemporal trend variability of SPEI and SPI was investigated at a significance level of 0.05 using the non-parametric Mann-Kendall (MK) test. SPEI adds the effect of temperature rise and deficit change on the drought occurrences of different classes. SPEI provides a better estimation of drought characteristics due to its consideration of temperature change in the drought severity. The more significant number of drying events accounted for a timescale of 3 months and 6 months, reflecting the higher variability of the seasonal fluctuation of water balance over the state. At 9-month and 12-month timescales, SPI and SPEI fluctuate gradually with considerable differences between the duration and severity of the drought event. This study reveals that there have been a substantial number of drought events over the state during the last two decades (2000 to 2018). The results conclude that the study area is at risk of erratic meteorological drought conditions where the western part of the study is worst affected compared to the eastern part of Uttar Pradesh (India).

Rapid detection of Salmonella enterica in leafy greens by a novel DNA microarray-based PathogenDx system.

The diverse matrices pose great challenges for rapid detection of low Salmonella level (<10 CFU) in fresh produce. The applicability of microarray-based PathogenDx system for detecting low contamination of Salmonella Newport from leafy greens was evaluated. A pre-PCR preparation protocol including enrichment in universal pre-enrichment broth for 3 h followed by sample concentration using an InnovaPrep bio-concentrator or 6 h enrichment without a concentration step was used for detecting S. Newport from leafy greens with initial inoculum level at ∼6 CFU/25 g. Among 205 samples tested, 98%, 93%, 76%, and 60% of Romaine lettuce, Iceberg lettuce, kale, and spinach samples were tested positive after 3 h of enrichment with sample concentration. After 6 h of enrichment, 100%, 98%, 90%, and 82% of Romaine lettuce, Iceberg lettuce, kale, and spinach samples were positive. The samples were parallelly tested by the FDA bacterial analytical manual (BAM) method and 100% of spiked produce samples were tested positive. The overall analysis time of this methodology was between 8 and 11 h, including all pre-enrichment and concentration steps, in contrast to 4-5 days required for BAM method. The system correctly differentiated all 108 Salmonella strains and 35 non-Salmonella strains used in the study. This novel microarray approach provides a rapid method for detecting Salmonella in leafy greens.

Biocontrol of Listeria monocytogenes and Salmonella enterica on Fresh Strawberries with Lactic Acid Bacteria During Refrigerated Storage.

Small fruits such as strawberries have been increasingly implicated in outbreaks of foodborne illnesses. Salmonella enterica and Listeria monocytogenes may contaminate strawberries leading to potential public health concern. The objective of this study was to investigate the efficacy of a combined lactic acid bacteria (LAB) treatment of Lactobacillus plantarum and Pediococcus pentosaceus for controlling S. enterica and L. monocytogenes on fresh strawberries during storage at 4°C and 10°C. Strawberries purchased from a local grocery store were separately dip inoculated with Salmonella Newport, Salmonella Tennessee, Salmonella Thompson, or a three-strain cocktail of L. monocytogenes at ∼9 log colony-forming unit (CFU)/mL and allowed to air-dry for 1 h. Inoculated strawberries were then divided into three groups: (1) Control (pathogen alone), (2) Man, Rogosa, Sharpe (MRS) control (dipping in MRS broth), and (3) LAB treatment (dipping in a LAB cocktail of L. plantarum and P. pentosaceus). After treatment, strawberries were stored at 4°C or 10°C for 7 d in vented clamshell containers. Surviving Listeria, Salmonella, and LAB populations on strawberries were determined on 0, 1, 3, and 7 d post-treatment by plating on selective agars. At both 4°C and 10°C, LAB treatment significantly decreased Listeria populations by up to 2 log CFU/g compared to controls after 3 d of storage (p < 0.05). When strawberries were stored at 4°C, LAB treatment reduced ∼2.5 log, ∼2.7 log, and ∼2.9 log CFU/g in Salmonella Newport, Salmonella Tennessee, and Salmonella Thompson populations, respectively, compared to control on day 7. Similarly, ∼2.5 log CFU/g reductions of Salmonella populations were observed with LAB treatment at 10°C on day 7. LAB populations remained at ∼7.5 log CFU/g levels on strawberries at both temperatures throughout the entire study. Results of this study suggest that a combined LAB treatment can be potentially used as biocontrol agents against Salmonella and L. monocytogenes on strawberries at postharvest level.

Discovery of a potent G-protein-coupled receptor 119 agonist for the treatment of type 2 diabetes.

The ever-growing prevalence of Type-2 diabetes in the world has an urgent need for multiple orally effective agents that can regulate glucose homeostasis. G-Protein coupled receptor 119 (GPR 119) agonists have demonstrated the glucose-dependent insulin secretion and showed beneficial effects on glycemic control in humans and/or relevant animal models. Herein, we describe our efforts towards identification of a potent and oral GPR 119 agonist 13c (ZY-G19), which showed in vitro potency in the cell-based assay and in vivo efficacy without exerting any significant signs of toxicity in relevant animal models.

Inhibition of Escherichia coli O157:H7 and Salmonella enterica virulence factors by benzyl isothiocyanate.

Escherichia coli O157:H7 and Salmonella enterica are foodborne pathogens with major public health concern in the U.S. These pathogens utilize several virulence factors to initiate infections in humans. The antimicrobial effect of seven glucosinolate hydrolysis compounds against Salmonella and E. coli O157:H7 was investigated by the disc diffusion assay. Among the tested compounds, benzyl isothiocyanate (BIT), which exerted the highest antimicrobial activity, was evaluated for its anti-virulence properties against these pathogens. The effect of BIT on motility of Salmonella and E. coli O157:H7 and Shiga toxin production by E. coli O157:H7 was determined by the motility assay and ELISA procedure, respectively. Confocal and transmission electron microscopy (TEM) procedures were used to determine bacterial damage at the cellular level. Results revealed that sub-inhibitory concentrations (SICs) of BIT significantly inhibited the motility of both bacteria (P < 0.05). Shiga toxin production by E. coli O157:H7 was decreased by ~32% in the presence of BIT at SICs. TEM results showed the disruption of outer membrane, release of cytoplasmic contents, and cell lysis following BIT treatment. Results suggest that BIT could be potentially used to attenuate Salmonella and E. coli O157:H7 infections by reducing the virulence factors including bacterial motility and Shiga toxin production.

Shifts in spinach microbial communities after chlorine washing and storage at compliant and abusive temperatures.

Fresh produce, like spinach, harbors diverse bacterial populations, including spoilage and potentially pathogenic bacteria. This study examined the effects of produce washing in chlorinated water and subsequent storage on the microbiota of spinach. Baby spinach leaves from a commercial fresh-cut produce processor were assessed before and after washing in chlorinated water, and then after one week's storage at 4, 10, and 15 °C. Microbial communities on spinach were analyzed by non-selective plating, qPCR, and 16S rDNA amplicon sequencing. Bacterial populations on spinach, averaging 6.12 ±â€¯0.61 log CFU/g, were reduced by 1.33 ±â€¯0.57 log after washing. However, populations increased by 1.77-3.24 log after storage, with larger increases occurring at higher temperature (15 > 10 > 4 °C). The predominant phylum identified on unwashed spinach leaves was Proteobacteria; dominant genera were Pseudomonas and Sphingomonas. Bacterial communities shifted significantly after chlorine washing and storage. Several Proteobacteria species, such as Stenotrophomonas sp. and Erwinia sp., were relatively tolerant of chlorine treatment, while species of Flavobacterium and Pedobacter (phylum Bacteroidetes) grew rapidly during storage, especially at abusive temperatures. Cupriavidus sp. and Ralstonia sp. showed significant increases after washing. After storage, microbial communities on spinach appeared to shift back toward the pre-washing distributions.

Inactivation of Escherichia coli O157:H7 and Salmonella on Fresh Herbs by Plant Essential Oils.

Consumer awareness of fresh herbs and its demand has increased in recent years due to health benefits and distinct aroma in prepared food. There are specific markets for local growers, especially for organically grown herbs. Shiga-toxigenic Escherichia coli and Salmonella spp. have been detected and associated with foodborne outbreaks from fresh herbs. Limited treatment options are available in the processing of fresh herbs to prevent the spread of foodborne pathogens. In this study, plant-based essential oils were evaluated on fresh herbs for their antimicrobial activities against Salmonella and E. coli O157:H7. Fresh herbs (basil, cilantro, dill, parsley, and tarragon) were inoculated with cocktails of either Salmonella or E. coli O157:H7 and then dip treated with chlorine (50 ppm), cinnamaldehyde (0.3 and 0.5%), and carvacrol (0.1 and 0.3%). Control herb samples were dipped in sterile water. Samples were collected on days 0, 2, 7, and 14 for enumeration of pathogens during 4°C storage. The bactericidal efficacy differed with herbs and antimicrobial concentrations. Treatments with 0.3% carvacrol or 0.5% cinnamaldehyde reduced E. coli O157:H7 and Salmonella by 5 log CFU/g (p > 0.05%) on cilantro and dill leaves from their initial inoculum level. Bactericidal efficacy of 0.1% carvacrol and 0.3% cinnamaldehyde was significant against Salmonella compared with chlorine on all herb leaves. E. coli O157:H7 and Salmonella populations were reduced further during storage of treated herbs. There was no visual difference in herbs treated with 0.3% cinnamaldehyde or 0.1% carvacrol from control samples. Results indicate that 0.3% cinnamaldehyde and 0.1% carvacrol are effective against E. coli O157:H7 and Salmonella, retain color attributes of fresh herbs, and, therefore, may be an alternative wash treatment for fresh herbs.

Identification of appropriate QTc formula in beagle dogs for nonclinical safety assessment.

A number of drugs belonging to different therapeutic classes cause increase in QT interval duration, and this change has been associated with ventricular arrhythmias. Investigation of changes in QT intervals in toxicity studies in dogs is therefore of potential value. Estimation of a direct effect of drugs on the duration of the QT interval can be confused by drug-induced increases in heart rate. The objective of this evaluation was to identify an appropriate correction formula by comparing different formulae that could appropriately correct changes in QT interval in conscious beagle dogs in toxicology studies. Most commonly used QTc (QT correction) formulae are derived from human observations, like Bazett's formula and thus are not applicable for other species like dogs, where the normal values of heart rate is higher compared to humans. Using our historical data, we have established and compared different correction formulas and found that Van de Water's formula is the most appropriate for dog under conditions stated. However, there is no universally accepted formula for QTc calculation in dogs, and hence each organization should have its own formula, based on the analysis of data obtained from the strain used in its own experimental conditions.

Inactivation of Listeria monocytogenes, Salmonella spp. and Escherichia coli O157:H7 on cantaloupes by octenidine dihydrochloride.

The efficacy of a new generation disinfectant, octenidine dihydrochloride (OH), as wash and coating treatments for reducing Listeria monocytogenes (LM), Salmonella spp. (SAL), and Escherichia coli O157:H7 (EC) on cantaloupe was investigated. Cantaloupe rind plugs inoculated separately with the three bacterial species (∼8 log CFU/cm(2)) were washed for 1, 3, 5 min at 25 °C in water, or chlorine (200 ppm), ethanol (1%), OH (0.01, 0.05, 0.1%) and surviving populations were measured after treatment. Additionally, inoculated cantaloupe rind plugs were coated with 2% chitosan or chitosan containing OH (0.01, 0.05, 0.1%) and sampled for surviving pathogens. Subsequently, the antimicrobial efficacy of OH wash and coating (0.1, 0.2%) on whole cantaloupes was determined. All OH wash reduced LM, SAL, and EC on cantaloupe rinds by > 5 log CFU/cm(2) by 2 min, and reduced populations to undetectable levels (below 2 log CFU/cm(2)) by 5 min (P < 0.05). Similarly, OH coating on cantaloupe rinds reduced the pathogens by 3-5 log /cm(2) (P < 0.05). Washing and coating whole cantaloupes with OH reduced the three pathogens by at least 5 log and 2 log CFU/cm(2), respectively (P < 0.05). Results suggest that OH could be used as antimicrobial wash and coating to reduce LM, SAL, and EC on cantaloupes.

Biofilm Formation by Environmental Isolates of Salmonella and Their Sensitivity to Natural Antimicrobials.

The objective of this study was to determine reduction of Salmonella in biofilms by essential oils. Biofilm formation of 15 Salmonella isolates from conventional swine farm environment was evaluated by 96-well microtiter plate crystal violet and minimum biofilm eradication concentration (MBEC) assays. Only one of the 15 isolates was a strong biofilm producer as classified by crystal violet assay. All Salmonella isolates formed biofilm on MBEC assay. The curli expression was robust among strains S322 and S435 (Salmonella Infantis), S644, S777, S931, S953, and S977 (Salmonella Typhimurium) as observed by Congo red dye binding assay. The cell hydrophobicity varied with strains and growth phase of the strain; however, there was no significant difference in hydrophobicity of these strains. Natural antimicrobials were evaluated with MBEC assay for their bactericidal efficacy in reducing Salmonella in biofilms. Cinnamaldehyde and sporran at 1000 ppm significantly reduced Salmonella in biofilms. The bactericidal effect of these antimicrobials increased with their concentrations. Salmonella were reduced by 6 log CFU from their initial populations of 7-7.5 log CFU/cm(2) when 2000 ppm concentration of these antimicrobials were used. Salmonella were undetectable when 3000 ppm of cinnamaldehyde or sporran was used. Natural antimicrobials such as cinnamaldehyde and sporran can be used to reduce Salmonella in biofilms.

Physical covering for control of Escherichia coli O157:H7 and Salmonella spp. in static and windrow composting processes.

This study investigated the effect of a 30-cm covering of finished compost (FC) on survival of Escherichia coli O157:H7 and Salmonella spp. in active static and windrow composting systems. Feedstocks inoculated with E. coli O157:H7 (7.41 log CFU/g) and Salmonella (6.46 log CFU/g) were placed in biosentry tubes (7.5-cm diameter, 30-cm height) at three locations: (i and ii) two opposing sides at the interface between the FC cover layer (where present) and the feedstock material (each positioned approximately 10 cm below the pile's surface) and (iii) an internal location (top) (approximately 30 cm below the surface). On specific sampling days, surviving populations of inoculated E. coli O157:H7 and Salmonella, generic E. coli, and coliforms in compost samples were determined. Salmonella spp. were reduced significantly within 24 h in windrow piles and were below the detection limit after 3 and 7 days at internal locations of windrow and static piles containing FC covering, respectively. Likewise, E. coli O157:H7 was undetectable after 1 day in windrow piles covered with finished compost. Use of FC as a covering layer significantly increased the number of days that temperatures in the windrows remained ≥55°C at all locations and in static piles at internal locations. These time-temperature exposures resulted in rapid reduction of inoculated pathogens, and the rate of bacterial reduction was rapid in windrow piles. The sample location significantly influenced the survival of these pathogens at internal locations compared to that at interface locations of piles. Finished compost covering of compost piles aids in the reduction of pathogens during the composting process.

Advances in the Study of Mirror Neurons and Their Impact on Neuroscience: An Editorial.

The mirror neurons are complex neuronal circuits in the brain, and they respond to the actions that we observe in others. The mirror neurons constitute a revolutionary discovery in the field of neuroscience that has not only reshaped our understanding of social cognition and empathetic behavior but also bridged gaps in our comprehension of the human brain's intricate workings. This article aims to distill the crux of these groundbreaking discoveries and their transformative ramifications regarding our perception of human interactions and the advancement of neurorehabilitation techniques. The integration of non-invasive and patient-centric therapies into clinical practice underscores the immense potential that research on mirror neurons holds in enhancing patient outcomes and quality care. Research in mirror neurons will contribute significantly to the field of neuroscience, specifically neurorehabilitation.

Using Bio-inline Reactor to Evaluate Sanitizer Efficacy in Removing Dual-species Biofilms Formed by Escherichia coli O157:H7 and Listeria monocytogenes.

The efficacy of a sanitizer in biofilm removal may be influenced by a combination of factors such as sanitizer exposure time and concentration, bacterial species, surface topography, and shear stresses. We employed an inline biofilm reactor to investigate the interactions of these variables on biofilm removal with chlorine. The CDC bioreactor was used to grow E. coli O157:H7 and L. monocytogenes biofilms as a single species or with Ralstonia insidiosa as a dual-species biofilm on stainless steel, PTFE, and EPDM coupons at shear stresses 0.368 and 2.462 N/m2 for 48 hours. Coupons were retrieved from a CDC bioreactor and placed in an inline biofilm reactor and 100, 200, or 500 ppm of chlorine was supplied for 1- and 4 min. Bacterial populations in the biofilms were quantified pre- and posttreatment by plating on selective media. After chlorine treatment, reduction (Log CFU/cm2) in pathogen populations obtained from three replicates was analyzed for statistical significance. A 1-min chlorine treatment (500 ppm), on dual-species E. coli O157:H7 biofilms grown at high shear stress of 2.462 N/m2 resulted in significant E. coli O157:H7 reductions on SS 316L (2.79 log CFU/cm2) and PTFE (1.76 log CFU/cm2). Similar trend was also observed for biofilm removal after a 4-min chlorine treatment. Single species E. coli O157:H7 biofilms exhibited higher resistance to chlorine when biofilms were developed at high shear stress. The effect of chlorine in L. monocytogenes removal from dual-species biofilms was dependent primarily on the shear stress at which they were formed rather than the surface topography of materials. Besides surface topography, shear stresses at which biofilms were formed also influenced the effect of sanitizer. The removal of E. coli O157:H7 biofilms from EPDM material may require critical interventions due to difficulty in removing this pathogen. The inline biofilm reactor is a novel tool to evaluate the efficacy of a sanitizer in bacterial biofilm removal.

A Literature Review on Holistic Well-Being and Dopamine Fasting: An Integrated Approach.

Popularly known as dopaminergic detox or dopamine fasting, it is a concept that aims at reducing dependence on instant satisfaction gratification and overstimulation to attain mental clarity, lessen anxiety, and be able to enjoy everyday events again. Digital detox has been a part of the dopamine fasting concept for several years now. However, some critics argue that this notion has no scientific proof behind it and may fail to deal with the problem of dopamine dysregulation. Some intense types of dopamine fasting which include extreme isolation or strict dieting can result in damage to mental health as well as physical fitness. The objective of the article is to understand what dopamine fasting means and see the literature and evidence available on the topic. Indexes like PubMed, Scopus, OVID, Embase, and Google Scholar were searched using the keywords to understand the existing knowledge about dopamine fasting. The literature review was then written to incorporate the understanding in a way that can be implemented practically. Recent studies have shown that individuals who engage in dopamine-fasting-like ideologies may experience reduced impulsive behaviors, increased focus on tasks, and reduced overwhelm. However, extreme forms of dopamine fasting can lead to feelings of loneliness, anxiety, and malnutrition, which can have detrimental effects on mental and physical health. Hence, the effects of dopamine fasting can vary greatly among individuals, and there is no one-size-fits-all approach. It is essential to consider individual needs and preferences when incorporating dopamine fasting into one's lifestyle and explore alternative practices that align with the principles of dopamine fasting. Understanding and respecting these differences is crucial in determining the most suitable strategies for maintaining a balanced dopamine response and overall psychological health. The benefits of dopamine fasting can be tremendous if done correctly but it depends on every individual to find the correct way and in the modern day, the practices can become tough to implement.

Exploring the Role of Circadian Rhythms in Sleep and Recovery: A Review Article.

Sleep is essential for every living organism. Humans spend about one-third of their lives sleeping. Sleep has been studied extensively, and the role of sleep in psychological, mental, and physical well-being is established to be the best. The rhythm of the brain between wakefulness and sleep is called the circadian rhythm, which is mainly controlled by melatonin and the pineal gland. The imbalance of this rhythm can lead to devastating effects on health. Vigorous workouts close to bedtime can interfere with falling asleep. Meal timing and composition can significantly affect sleep quality. It is advised to avoid large meals, caffeine, and alcohol before bedtime. Heavy meals close to bedtime can lead to poor sleep and hormone disruption. By following these guidelines enumerated in the article, individuals can improve sleep quality and overall health. Sleep cycles, especially rapid eye movement sleep, have a profound influence on mental and physical health. Adhering to recommended sleep practices enhances bodily restoration, fortifies the immune system, and upholds metabolic equilibrium. Sleep hygiene aligned with circadian rhythms is crucial for disease prevention and well-being. Healthcare professionals should prioritize sleep optimization strategies for patient care and public health.

A Comprehensive Review on Digital Detox: A Newer Health and Wellness Trend in the Current Era.

This research investigates the effects of an electronic detox treatment on the utilization of social media and smartphones, addiction levels, and the general health of individuals. Remarkably, individuals discovered that the digital detox was less challenging than anticipated, with a significant number expressing sensations of pleasure and alleviation. Although a few individuals encountered instances of alienation and solitude, the majority managed to adapt to the limited availability of the internet. Notably, individuals saw heightened tedium and replaced their use of social networking sites with additional tasks using screens. After the procedure, measures demonstrated favorable or neutral enhancements in addictions and health-related results. The quantitative findings indicate an increased understanding of online conduct and the use of self-regulating strategies. Concrete recommendations put forward by respondents include reducing stringent deadlines, implementing personalized limitations, and devising tactics to regulate alerts and their use. These observations may be used to shape subsequent digital detox programs in order to improve their efficacy and increase participation from participants.