From Alzheimer's Disease to Anxiety, Epilepsy to Schizophrenia: A Comprehensive Dive Into Neuro-Psychiatric Disorders.

This comprehensive narrative review endeavors to dissect the intricate web of neuropsychiatric disorders that significantly impact cognition, emotion regulation, behavior, and mental health. With a keen focus on Alzheimer's disease (AD), anxiety disorders, epilepsy, schizophrenia, and autism spectrum disorder (ASD), this article delves into their underlying mechanisms, clinical presentations, diagnostic challenges, and therapeutic interventions. Highlighting the considerable disability and societal costs that these conditions impose, it reflects on the over six million individuals grappling with Alzheimer's, the 19 million American adults living with anxiety disorders, the three million with epilepsy, and the global reach of schizophrenia affecting approximately 20 million people. Furthermore, it examines the emerging landscape of ASD, noting the escalating diagnosis rates and the pressing need for innovative treatments and equitable healthcare access. Through a detailed exploration of current research, technological innovations, and the promise of personalized medicine, this review aims to illuminate the complexities of these conditions, advocate for early intervention strategies, and call for a unified approach to tackling the multifaceted challenges they present. The ultimate goal is to inform and inspire healthcare professionals, researchers, and policymakers to foster advancements that improve outcomes and quality of life for individuals affected by these profound neuropsychiatric disorders, steering towards a future where these conditions are no longer insurmountable.

Nuclear Cardiology in the Era of Precision Medicine: Tailoring Treatment to the Individual Patient.

Nuclear cardiology, employing advanced imaging technologies like positron emission tomography (PET) and single photon emission computed tomography (SPECT), is instrumental in diagnosing, risk stratifying, and managing heart diseases. Concurrently, precision medicine advocates for treatments tailored to each patient's genetic, environmental, and lifestyle specificities, promising a revolution in personalized cardiovascular care. This review explores the synergy between nuclear cardiology and precision medicine, highlighting advancements, potential enhancements in patient outcomes, and the challenges and opportunities of this integration. We examined the evolution of nuclear cardiology technologies, including PET and SPECT, and their role in cardiovascular diagnostics. We also delved into the principles of precision medicine, focusing on genetic and molecular profiling, data analytics, and individualized treatment strategies. The integration of these domains aims to optimize diagnostic accuracy, therapeutic interventions, and prognostic evaluations in cardiovascular care. Advancements in molecular imaging and the application of artificial intelligence in nuclear cardiology have significantly improved the precision of diagnostics and treatment plans. The adoption of precision medicine principles in nuclear cardiology enables the customization of patient care, leveraging genetic information and biomarkers for enhanced therapeutic outcomes. However, challenges such as data integration, accessibility, cost, and the need for specialized expertise persist. The confluence of nuclear cardiology and precision medicine offers a promising pathway toward revolutionizing cardiovascular healthcare, providing more accurate, effective, and personalized patient care. Addressing existing challenges and fostering interdisciplinary collaboration is crucial for realizing the full potential of this integration in improving patient outcomes.

The Potential of Fecal and Urinary Biomarkers for Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer often diagnosed at advanced stages, highlighting the urgent need for early detection strategies. This systematic review explores the potential of fecal and urinary biomarkers for early PDAC detection. A comprehensive search identified eight relevant studies investigating various biomarkers, including proteins, metabolites, microbial profiles, DNA mutations, and non-coding RNAs. Promising findings suggest that urinary biomarkers related to metabolic alterations, inflammatory processes, fecal microbiome profiles, and fecal miRNAs hold diagnostic potential even at early stages of PDAC. Combining biomarkers into panels may enhance diagnostic accuracy. Challenges such as validation in larger cohorts, standardization of protocols, and regulatory approval must be addressed for clinical translation. Despite these hurdles, non-invasive urinary and fecal biomarkers represent a promising avenue for improving PDAC outcomes through early detection.

Evaluating the Efficacy of Antioxidant Therapy in Enhancing the Quality of Life of Chronic Pancreatitis Patients: A Systematic Review.

Chronic pancreatitis (CP), an inflammatory disease characterized by irreversible pancreatic changes and progressive fibrosis, significantly impairs patients' quality of life. This systematic review aims to assess the efficacy of antioxidant therapy in enhancing the quality of life of CP patients. Focusing on the role of oxidative stress in CP pathogenesis, we explored several databases for studies evaluating the impact of antioxidant supplementation. The review included randomized controlled trials and cohort studies reporting pain frequency, intensity, and overall quality of life measures. Findings from these studies present a mixed view of the efficacy of antioxidants in CP, with some suggesting benefits in symptom management, while others show inconsistency in improving patient outcomes. The review concludes that while antioxidant therapy holds potential, especially in symptom alleviation, there is a need for more rigorous, larger-scale studies to confirm its effectiveness in CP management and to establish standardized treatment protocols. The incorporation of antioxidants into CP treatment plans should be approached with personalized care, considering the varied responses observed in different patient populations.

The Revival of Essay-Type Questions in Medical Education: Harnessing Artificial Intelligence and Machine Learning.

OBJECTIVE: To analyse and compare the assessment and grading of human-written and machine-written formative essays. STUDY DESIGN: Quasi-experimental, qualitative cross-sectional study. Place and Duration of the Study: Department of Science of Dental Materials, Hamdard College of Medicine & Dentistry, Hamdard University, Karachi, from February to April 2023. METHODOLOGY: Ten short formative essays of final-year dental students were manually assessed and graded. These essays were then graded using ChatGPT version 3.5. The chatbot responses and prompts were recorded and matched with manually graded essays. Qualitative analysis of the chatbot responses was then performed. RESULTS: Four different prompts were given to the artificial intelligence (AI) driven platform of ChatGPT to grade the summative essays. These were the chatbot's initial responses without grading, the chatbot's response to grading against criteria, the chatbot's response to criteria-wise grading, and the chatbot's response to questions for the difference in grading. Based on the results, four innovative ways of using AI and machine learning (ML) have been proposed for medical educators: Automated grading, content analysis, plagiarism detection, and formative assessment. ChatGPT provided a comprehensive report with feedback on writing skills, as opposed to manual grading of essays. CONCLUSION: The chatbot's responses were fascinating and thought-provoking. AI and ML technologies can potentially supplement human grading in the assessment of essays. Medical educators need to embrace AI and ML technology to enhance the standards and quality of medical education, particularly when assessing long and short essay-type questions. Further empirical research and evaluation are needed to confirm their effectiveness. KEY WORDS: Machine learning, Artificial intelligence, Essays, ChatGPT, Formative assessment.

Formulation of sumatriptan succinate orodispersible tablets using chitosan and sodium starch glycolate for immediate migraine relief.

Migraine is one of the common neurological disease affecting around 23% of the Pakistani population. Prompt treatment is required to regain the functional ability of patients. The present study was designed to develop sumatriptan succinate orodispersible tablets that would quickly overcome acute migraine episodes using 22 full-factorial design. The chitosan and sodium starch glycolate were taken as independent variables; friability, disintegration, dispersion time and water absorption ratio as response variables. Eight trial formulations were generated by Design Expert® software. The main effect plots were used to check the interaction of formulations with response variables. All trial formulations showed good micromeritic properties in terms of angle of repose (19.59o-24.57°), Carr's index (17.08-24.90%) and Hausner's ratio (1.20-1.33). The tablets wetted quickly (17.1- 39 sec) in dispersion medium, showed higher water absorption ratio (188-341 sec) and disintegrated quickly (13-20 sec) with an excellent dissolution rate (94-99%). The main effect plots show interactions between the independent variables against most of the study responses. A 22 full-factorial model was found to be effective in studying the influence of formulation variables on response parameters. Both chitosan and sodium starch glycolate can be used in combination to fabricate an effective orodispersible formulation of sumatriptan succinate.

Enhancing storage and gastroprotective viability of Lactiplantibacillus plantarum encapsulated by sodium caseinate-inulin-soy protein isolates composites carried within carboxymethyl cellulose hydrogel.

Probiotics are subjected to various edible coatings, especially proteins and polysaccharides, which serve as the predominant wall materials, with ultrasound, a sustainable green technology. Herein, sodium caseinate, inulin, and soy protein isolate composites were produced using multi-frequency ultrasound and utilized to encapsulateLactiplantibacillus plantarumto enhance its storage, thermal, and gastrointestinal viability. The physicochemical analyses revealed that the composites with 5 % soy protein isolate treated with ultrasound at 50 kHz exhibited enough repulsion forces to maintain stability, pH resistance, and the ability to encapsulate larger particles and possessed the highest encapsulation efficiency (95.95 %). The structural analyses showed changes in the composite structure at CC, CH, CO, and amino acid residual levels. Rheology, texture, and water-holding capacity demonstrated the production of soft hydrogels with mild chewing and gummy properties, carried the microcapsules without coagulation or sedimentation. Moreover, the viability attributes ofL. plantarumevinced superior encapsulation, protecting them for at least eight weeks and against heat (63 °C), reactive oxidative species (H2O2), and GI conditions.

Novel drug discovery: Advancing Alzheimer's therapy through machine learning and network pharmacology.

Alzheimer's disease (AD), marked by tau tangles and amyloid-beta plaques, leads to cognitive decline. Despite extensive research, its complex etiology remains elusive, necessitating new treatments. This study utilized machine learning (ML) to analyze compounds with neuroprotective potential. This approach exposed the disease's complexity and identified important proteins, namely MTOR and BCL2, as central to the pathogenic network of AD. MTOR regulates neuronal autophagy and survival, whereas BCL2 regulates apoptosis, both of which are disrupted in AD. The identified compounds, including Armepavine, Oprea1_264702,1-cyclopropyl-7-fluoro-8-methoxy-4-oxoquinoline-3-carboxylic acid,(2S)-4'-Hydroxy-5,7,3'-trimethoxyflavan,Oprea1_130514,Sativanone,5-hydroxy-7,8-dimethoxyflavanone,7,4'-Dihydroxy-8,3'-dimethoxyflavanone,N,1-dicyclopropyl-6,Difluoro-Methoxy-Gatifloxacin,6,8-difluoro-1-(2-fluoroethyl),1-ethyl-6-fluoro-7-(4-methylpiperidin-1-yl),Avicenol C, demonstrated potential modulatory effects on these proteins. The potential for synergistic effects of these drugs in treating AD has been revealed via network pharmacology. By targeting numerous proteins at once, these chemicals may provide a more comprehensive therapeutic approach, addressing many aspects of AD's complex pathophysiology. A Molecular docking, dynamic simulation, and Principle Component Analysis have confirmed these drugs' efficacy by establishing substantial binding affinities and interactions with important proteins such as MTOR and BCL2. This evidence implies that various compounds may interact within the AD pathological framework, providing a sophisticated and multifaceted therapy strategy. In conclusion, our study establishes a solid foundation for the use of these drugs in AD therapy. Thus current study highlights the possibility of multi-targeted, synergistic therapeutic approaches in addressing the complex pathophysiology of AD by integrating machine learning, network pharmacology, and molecular docking simulations. This holistic technique not only advances drug development but also opens up new avenues for developing more effective treatments for this difficult and widespread disease.

Role of small molecules as drug candidates for reprogramming somatic cells into induced pluripotent stem cells: A comprehensive review.

With the use of specific genetic factors and recent developments in cellular reprogramming, it is now possible to generate lineage-committed cells or induced pluripotent stem cells (iPSCs) from readily available and common somatic cell types. However, there are still significant doubts regarding the safety and effectiveness of the current genetic methods for reprogramming cells, as well as the conventional culture methods for maintaining stem cells. Small molecules that target specific epigenetic processes, signaling pathways, and other cellular processes can be used as a complementary approach to manipulate cell fate to achieve a desired objective. It has been discovered that a growing number of small molecules can support lineage differentiation, maintain stem cell self-renewal potential, and facilitate reprogramming by either increasing the efficiency of reprogramming or acting as a genetic reprogramming factor substitute. However, ongoing challenges include improving reprogramming efficiency, ensuring the safety of small molecules, and addressing issues with incomplete epigenetic resetting. Small molecule iPSCs have significant clinical applications in regenerative medicine and personalized therapies. This review emphasizes the versatility and potential safety benefits of small molecules in overcoming challenges associated with the iPSCs reprogramming process.

From Sugar Spikes to Pressure Peaks: Navigating the World of Diabetes, Hypertension, Obesity, and Kidney Health.

Diabetes, hypertension, obesity, and chronic kidney disease (CKD) are major public health challenges globally, contributing significantly to morbidity and mortality. The co-occurrence and interplay among these conditions exacerbate health outcomes, highlighting the need for an integrated understanding and approach to management. This narrative review aims to explore the complex relationships between diabetes, hypertension, obesity, and CKD, elucidating their collective impact on health. It discusses the epidemiological trends, underlying pathophysiological mechanisms, genetic predispositions, current treatment strategies, and the future direction of research and therapy. An extensive review of current literature was conducted, focusing on the epidemiology, pathophysiology, risk factors, diagnosis, and treatment of diabetes, hypertension, obesity, and CKD. Additionally, the review delves into the genetic and molecular biology underlying these conditions, the potential for personalized medicine, and the importance of a multidisciplinary approach to care. The review identifies key areas where these conditions intersect, enhancing disease progression and complicating management. It highlights the role of genetic and environmental factors in disease etiology, the critical need for personalized treatment strategies, and the gaps in current management approaches. Innovations in pharmacotherapy, monitoring technologies, and the potential of pharmacogenomics are discussed as avenues for advancing patient care. Diabetes, hypertension, obesity, and CKD are intricately linked, necessitating an integrated, patient-centered approach to care that goes beyond traditional treatment modalities. Future research should focus on collaborative models and interdisciplinary strategies to address the multifaceted challenges posed by these conditions. Emphasizing personalized medicine and leveraging technological advancements offer promising pathways to improve outcomes and reduce the global health burden of these metabolic disorders.

Development of an AI-based image/ultrasonic convergence camera system for accurate gas leak detection in petrochemical plants.

Outdoor pipeline leaks are difficult to accurately measure using existing concentration measurement systems installed in petrochemical plants owing to external air currents. Besides, leak detection is only possible for a specific gas. The purpose of this study was to develop an image/ultrasonic convergence camera system that incorporates artificial intelligence (AI) to improve pipe leak detection and establish a real-time monitoring system. Our system includes an advanced ultrasonic camera coupled with a deep learning-based object-detection algorithm trained on pipe image data from petrochemical plants. The collected data improved the accuracy of detected gas leak localization through deep learning. Our detection model achieves an mAP50 (Mean average precision calculated at an intersection over union (IoU) threshold of 0.50)score of 0.45 on our data and is able to detect the majority of leak points within a system. The petrochemical plant environment was simulated by visiting petrochemical plants and reviewing drawings, and an outdoor experimental demonstration site was established. Scenarios such as flange connection failure were set under medium-/low-pressure conditions, and the developed product was experimented under gas leak conditions that simulated leakage accidents. These experiments enabled the removal of potentially confounding surrounding noise sources, which led to the false detection of actual gas leaks using the AI piping detection technique.

Impact of Preoperative Nutritional Support on Surgical Outcomes in Gastrointestinal Surgeries: A Systematic Review.

Malnutrition presents a significant risk to patients undergoing gastrointestinal surgery, with direct consequences on postoperative complication rates, recovery times, and mortality. Our systematic review, guided by PRISMA protocols, examined the impact of preoperative nutritional support on these surgical outcomes. We scrutinized publications from PubMed, Medline, Embase, and the Cochrane Library up to April 2023, including randomized controlled trials, cohort studies, and systematic reviews. The stringent selection process narrowed to 10 studies demonstrating the efficacy of preoperative nutritional support, from oral supplements to enteral and parenteral nutrition, in reducing postoperative complications and length of hospital stays while enhancing recovery rates. The benefits varied, indicating a pressing need for customized nutritional regimens based on patient demographics and surgical specifics. Our findings advocate incorporating individualized nutritional strategies into preoperative care, enhancing patient outcomes. Future research should aim to refine these strategies, focusing on the optimal timing, duration, and type of nutritional support.

The Potential of Salivary Biomarkers in Early Detection of Pancreatic Ductal Adenocarcinoma: A Systematic Review.

Pancreatic ductal adenocarcinoma (PDAC) is a formidable global health concern with a dire prognosis, highlighting the critical need for early detection strategies. This systematic review delves into the potential of salivary biomarkers as a non-invasive means for identifying PDAC at its incipient stages. Saliva's proximity to the circulatory system enables the detection of tumor-derived biomolecules, making it an ideal candidate for mass screening. The analysis of three selected studies reveals promising candidates such as Neisseria mucosa, Fusobacterium periodonticum, polyamines, and specific long non-coding RNAs (lncRNAs). Notably, polyamines like spermine show potential in distinguishing PDAC, while lncRNAs HOX transcript antisense RNA (HOTAIR) and plasmacytoma variant translocation 1 (PVT1) exhibit superior sensitivity and specificity compared to traditional serum markers. However, challenges, including small sample sizes and a lack of validation, underscore the need for standardized diagnostic panels and large-scale collaborative studies. Advancements in nanotechnology, machine learning, and ethical considerations are crucial for harnessing the diagnostic potential of saliva. The review emphasizes the imperative for extensive clinical trials to validate salivary biomarkers, ensuring not only diagnostic accuracy but also cost-effectiveness, patient compliance, and long-term benefits in the realm of PDAC screening. Longitudinal studies are recommended to unravel temporal changes in salivary biomarkers, shedding light on disease progression and treatment response.

Navigating the Surgical Landscape: A Comprehensive Analysis of Endoscopic vs. Microscopic Transsphenoidal Pituitary Surgery Outcomes.

Pituitary surgery, a critical intervention for various pituitary disorders, has sparked ongoing debates regarding the preference between endoscopic and microscopic transsphenoidal approaches. This systematic review delves into the outcomes associated with these techniques, taking into account the recent advancements in neurosurgery. The minimally invasive nature of endoscopy, providing improved visualization and reduced morbidity, stands in contrast to the well-established track record of the conventional microscopic method. Examining outcomes for disorders such as Cushing's disease and acromegaly, the review synthesizes evidence from Denmark, Bulgaria, and China. Noteworthy advantages of endoscopy encompass higher resection rates, shorter surgery durations, and fewer complications, endorsing its effectiveness in pituitary surgery. While emphasizing the necessity for prospective trials, the review concludes that endoscopic approaches consistently showcase favorable outcomes, influencing the ongoing discourse on the optimal surgical strategies for pituitary disorders.

Surgical Interventions in Chronic Pancreatitis: A Systematic Review of Their Impact on Quality of Life.

This systematic review evaluates the efficacy of surgical interventions in improving the quality of life for patients with chronic pancreatitis (CP). A thorough literature search, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, identified 11 studies that focused on patient-reported outcomes after surgical treatments, including pancreatic resections, drainage procedures, and duodenum-preserving head resections. The findings indicate that organ-preserving procedures, notably the Frey and Beger operations, significantly enhance pain control and overall quality of life while reducing analgesic dependency. This review provides crucial insights into the long-term efficacy and comparative benefits of different surgical approaches, highlighting the need for personalized surgical strategies in CP management. It emphasizes the necessity for standardized outcome measures and further comparative research to refine CP treatment protocols.

Influence of Nutritional Interventions on Functional Outcomes in Stroke Rehabilitation: A Systematic Review.

Stroke, a major cause of disability worldwide, necessitates comprehensive rehabilitation, with nutrition playing a pivotal role in recovery. Our systematic review assesses the impact of nutritional interventions on stroke survivors' rehabilitation. Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, we systematically searched PubMed, Embase, Web of Science, and Scopus, using keywords related to stroke rehabilitation and nutrition. Studies were selected based on criteria emphasizing dietary interventions and their effect on functional recovery in stroke patients. The review involved detailed data extraction and synthesis, covering study design, participant characteristics, interventions, and outcomes. Five studies met our inclusion criteria, encompassing longitudinal and prospective studies, retrospective cohorts, and randomized controlled trials. These studies highlighted the importance of early nutritional assessment, particularly for sarcopenic patients, and the role of energy and protein intake soon after a stroke. Findings indicated high nutritional risk correlated with poorer functional outcomes and increased inflammation. Tailored dietary support appeared beneficial for muscle mass maintenance and overall functional recovery, especially in older patients. Our review emphasizes the critical role of nutritional interventions in stroke rehabilitation. It suggests that personalized nutritional strategies can positively impact functional recovery, notably in older and nutritionally vulnerable stroke survivors. These insights underscore the necessity of integrating dietary assessments and interventions into standard stroke rehabilitation protocols, advocating a holistic approach to patient care.

Ferroptosis and Triple-Negative Breast Cancer: A Systematic Overview of Prognostic Insights and Therapeutic Potential.

In the realm of oncology, the prognosis and treatment of triple-negative breast cancer (TNBC) have long been challenges for researchers and clinicians. Characterized by its aggressive nature and limited therapeutic options, TNBC demands innovative approaches to understanding its underlying mechanisms and improving patient outcomes. One such avenue of exploration that has emerged in recent years is the study of ferroptosis, a form of regulated cell death driven by iron-dependent lipid peroxidation. Ferroptosis has garnered increasing attention due to its potential relevance in the context of TNBC. This systematic review aims to shed light on the intricate interplay between ferroptosis and the prognosis of TNBC. The article delves into a comprehensive examination of the existing literature to provide a holistic understanding of the subject. By investigating ferroptosis as both an intervention and a prognostic factor in TNBC, this article seeks to unravel its potential as a therapeutic target and prognostic marker. The emerging evidence and heterogeneity of ferroptosis in TNBC underscore the need for a systematic approach to assess its impact on patient outcomes. This review will serve as a valuable resource for researchers, clinicians, and healthcare professionals striving to enhance our knowledge of TNBC and explore novel avenues for prognosis and treatment.

Smoke Signals: Unraveling the Paradoxical Impact of Smoking on Stroke Prognosis and Treatment Efficacy.

Smoking is a well-established risk factor for stroke, yet its impact on stroke prognosis remains complex and multifaceted. This systematic review aims to elucidate the relationship between smoking and various stroke outcomes, including response to treatment and long-term recovery. We conducted a comprehensive analysis of four fundamental studies that examined the prognosis of stroke in smokers, focusing on clinical outcomes post-endovascular treatment, response to antiplatelet therapy, incidence of post-stroke delirium, and the effectiveness of thrombolysis treatment. The studies varied in design, including observational, retrospective, and post hoc trial analyses. The review reveals that smoking may paradoxically predict better clinical outcomes in specific treatment scenarios, such as post-endovascular treatment and when using clopidogrel. However, smokers also demonstrated higher rates of ischemic stroke and post-stroke delirium. Notably, the smoker's paradox in thrombolysis treatment was not supported. These findings highlight the need for personalized treatment approaches based on smoking status. Smoking has a complex and significant impact on stroke prognosis. While some benefits in specific treatment contexts were observed, the overall evidence strongly advises against smoking due to its adverse health consequences. This review underscores the importance of personalized stroke management in smokers and the integration of smoking cessation programs in post-stroke care. Future research should focus on larger, longitudinal studies to explore these associations further.

Corrigendum: Probiotics: mechanism of action, health benefits and their application in food industries.

[This corrects the article DOI: 10.3389/fmicb.2023.1216674.].

The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs.

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.