Supplementary Treatment Research Articles

Equine-Facilitated Psychotherapy as a Supplementary Treatment for Patients with Mental and/or Substance Use Disorders: An Observational Study on Treatment Outcome

Abstract This study examines whether adult patients (n = 105) with mental and/or substance use disorders benefit from equine-facilitated psychotherapy (EFP)—therapy with horses—in addition to regular treatment. The study used an observational pre-post-study design with two measurement points. Treatment outcomes were measured using standardized self-report instruments reflecting psychological distress (Hopkins Symptom Checklist-10), self-efficacy (General Self-Efficacy Scale-5), quality of life (Quality of Life-5), and emotion regulation (sub-scale from the Severity Indices of Personality Problems-118). All outcome measurements found statistically significant pre-post improvements after the EFP treatment program. The findings suggest that EFP could be a beneficial supplementary treatment for a broad range of patients with mental and/or substance use disorders. However, this observational study cannot establish causation or eliminate confounding variables.

Financial Incentives, Income Supplementation, Cash Transfer, and Universal Basic Income Interventions in Diabetes: Understanding Differences and Effectiveness: A Scoping Review.

The objective of this review is to evaluate and summarize the evidence base for the effects of monetary intervention approaches (the use of positive monetary reinforcers and gains) on diabetes outcomes. A reproducible search using OVID Medline, PubMed, Scopus, and CINAHL was conducted. Articles published from database creation up to July 2024 were searched. Outcomes included hemoglobin A1c (HbA1c), LDL, BMI, blood pressure, quality of life (QOL), psychosocial factors, self-care behaviors, and diabetes complications. A total of 13 articles met inclusion criteria and were included for final synthesis. Looking at the monetary approach across each study, eight used financial incentives, three used a form of income supplementation, one used cash transfers, and one used a combination of income supplementation and financial incentives. Ten of the 13 studies found statistically significant and clinically meaningful changes in HbA1c. For participants receiving interventions, change in HbA1c ranged from 0.19% to 1.74% for interventions incorporating financial incentives, 0.7% to 1.3% for interventions incorporating income supplementation, and 0.2% to 0.7% for the study incorporating cash transfers. Overall, evidence supports the relationship between monetary approaches, diabetes-related outcomes, and self-care behaviors across monetary approaches. Future studies should consider comparison between different monetary approaches using designs that will allow identification of effective strategies. As these approaches are theoretically and structurally different, pathways identifying the underlying mechanisms of change are greatly needed to advance the field.

LEDs supplemental light treatment promotes flowering and increases yield of ‘Kuemsil’ strawberries

LEDs supplemental light treatment promotes flowering and increases yield of ‘Kuemsil’ strawberries

Propensity score matched cohort study on magnesium supplementation and mortality in critically ill patients with HFpEF

Heart failure with preserved ejection fraction (HFpEF) emerges as a singular subclass of heart failure, bereft of specific therapeutic options. Magnesium, an indispensable trace element, is essential to the preservation of cardiac integrity. However, the association between magnesium supplementation and mortality in HFpEF patients remains unclear. This study extracted HFpEF patient data from the MIMIC-IV database between 2008 and 2019. Propensity score matching was conducted to ensure that patients receiving magnesium supplementation (including magnesium sulfate and magnesium oxide) were balanced with those not receiving it in terms of baseline characteristics. The primary analysis focused on the 28-day all-cause mortality rate, with secondary endpoints encompassing ICU and one-year mortality rates, along with the duration of hospitalization. After matching, the study’s final cohort balanced at 1970 patients, with 985 patients per group. The results showed that magnesium intake significantly contributed to a decrease in the 28-day all-cause mortality rate (hazard ratio [HR], 0.682; 95% confidence interval [CI], 0.539–0.863), particularly in subgroups such as older patients (HR, 0.65; 95% CI 0.52–0.81), females (HR, 0.55; 95% CI 0.41–0.73), and those with hypertension (HR, 0.62; 95% CI 0.48–0.79) or without diabetes (HR, 0.54; 95% CI 0.41–0.71). Although magnesium treatment improved both ICU and one-year mortality rates, it concurrently resulted in extended ICU and hospital stays. Mediation analysis indicated that blood urea nitrogen partially mediated the association between magnesium intake and mortality, accounting for approximately 22.73% of the observed effect. Magnesium supplementation has illustrated a significant potential for mitigating the mortality rate in the HFpEF patient, particularly among the elderly, female, and individuals with hypertension. Therefore, magnesium supplementation stands as a potentially valuable supplementary treatment modality for patients with HFpEF. Further comprehensive research is warranted to explore its effects more deeply.

Supplementary Treatment for Alleviating Pain and Enhancing Functional Ability in Geriatric Patients with Osteoarthritis

Background and Objectives: A degenerative joint disease that primarily affects elderly individuals, osteoarthritis (OA) causes pain, decreased mobility, and a lower quality of life. Procaine is regarded as a “veteran” medicine due to its extensive clinical use, although it remains a molecule of interest, as researchers are uncovering new biological and pharmacological effects through innovative experimental methods. This study evaluates the efficacy of the “procaine complex”, developed in our country, in alleviating pain and improving functionality in elderly individuals with osteoarthritis of the knee and hip. Materials and Methods: We conducted an assessment of a longitudinal short-term study involving 177 patients aged 65 and older, who were randomly divided into two groups. One group received physical therapy and “procaine complex” periarticular injections (n = 101), while the other group received just physical therapy (n = 76). We assessed pain using a visual analog scale (VAS), in addition to functional evaluations using the Lequesne Index, Activities of Daily Living (ADL), and Instrumental ADL (IADL) scores. We evaluated these through a CGA (complex geriatric assessment), the walk test, “Up and Go” test, Mini Mental State (MMSE) and Geriatric Depression Scale (GDS) for cognitive status. We analyzed all the data from this study using PSPP v3 software. Results: The procaine complex treatment group exhibited a significant reduction in pain (p < 0.001) and improvement in daily activities (p < 0.001) relative to the control group. However, there was no notable difference in walking test scores (p = 0.171). No substantial detrimental effects were identified. The procaine complex did not surpass physical therapy in reducing depressive disorders, but both groups showed some enhancement in this regard. Conclusions: This study demonstrates an innovative approach to pain management by integrating periarticular “procaine complex” injections with physical therapy. This provides elderly individuals experiencing osteoarthritis pain and functional limitations with a secure and efficacious alternative to surgery, or may diminish years of disability.

The Trifecta of Industry, Academic, and Health System Partnership to Improve Mental Health Care Through Smartphone-Based Remote Patient Monitoring: Development and Usability Study.

Mental health treatment is hindered by the limited number of mental health care providers and the infrequency of care. Digital mental health technology can help supplement treatment by remotely monitoring patient symptoms and predicting mental health crises in between clinical visits. However, the feasibility of digital mental health technologies has not yet been sufficiently explored. Rhythms, from the company Health Rhythms, is a smartphone platform that uses passively acquired smartphone data with artificial intelligence and predictive analytics to alert patients and providers to an emerging mental health crisis. The objective of this study was to test the feasibility and acceptability of Rhythms among patients attending an academic psychiatric outpatient clinic. Our group embedded Rhythms into the electronic health record of a large health system. Patients with a diagnosis of major depressive disorder, bipolar disorder, or other mood disorder were contacted online and enrolled for a 6-week trial of Rhythms. Participants provided data by completing electronic surveys as well as by active and passive use of Rhythms. Emergent and urgent alerts were monitored and managed according to passively collected data and patient self-ratings. A purposively sampled group of participants also participated in qualitative interviews about their experience with Rhythms at the end of the study. Of the 104 participants, 89 (85.6%) completed 6 weeks of monitoring. The majority of the participants were women (72/104, 69.2%), White (84/104, 80.8%), and non-Hispanic (100/104, 96.2%) and had a diagnosis of major depressive disorder (71/104, 68.3%). Two emergent alerts and 19 urgent alerts were received and managed according to protocol over 16 weeks. More than two-thirds (63/87, 72%) of those participating continued to use Rhythms after study completion. Comments from participants indicated appreciation for greater self-awareness and provider connection, while providers reported that Rhythms provided a more nuanced understanding of patient experience between clinical visits. Rhythms is a user-friendly, electronic health record-adaptable, smartphone-based tool that provides patients and providers with a greater understanding of patient mental health status. Integration of Rhythms into health systems has the potential to facilitate mental health care and improve the experience of both patients and providers.

Assessing the Effectiveness of Add-On Therapy of Palmitoylethanolamide to Standard Therapy in Diabetic Peripheral Neuropathy

Background: Diabetic Peripheral Neuropathy (DPN) is a common yet challenging complication of diabetes, particularly in managing neuropathic pain. Palmitoylethanolamide (PEA), a naturally occurring nutraceutical from the ALIAmides group, has demonstrated potential for pain modulation, inflammation reduction, and improving quality of life. Method: A 9-month prospective observational study at PSG Hospital evaluated the impact of adding oral capsule PEA (708 mg in two divided doses) to standard therapy for DPN patients unresponsive to maximum tolerated dosages of Gabapentin, Pregabalin, amitriptyline, or duloxetine. The outcomes were the pain severity and quality of life. Pain was assessed using the Visual Analog Scale (VAS), sensitivity was evaluated via monofilament testing, and quality of life was measured using the American Chronic Pain Association (ACPA) Quality of Life Scale (QOLS). Results: Sixty patients with DPN were treated with adjunctive PEA and monitored for 8 weeks. Pain scores decreased significantly (6.05±1.096 to 4.15±1.233 at 4 weeks and 3.57±1.155 at 8 weeks, p˂0.05). Sensitivity improved via monofilament testing (7.12±1.58 to 9.43±0.78). Quality of life scores rose from 7.67 to 9.41 at 4 weeks and 9.68 at 8 weeks, indicating notable benefits. Conclusion: PEA proved effective as a supplemental treatment for nonresponsive DPN patients, yielding significant reductions in pain, enhanced sensitivity, and better quality of life. Importantly, no side effects were reported, affirming its tolerability and safety.

Factors associated with knowledge and practice regarding oxygen administration: A cross-sectional study among registered nurses working in wards and ICUs at Muhimbili National Hospital in Dar es Salaam, Tanzania.

Oxygen is a vital therapy approved by WHO, crucial for critically ill patients as a supplemental treatment. Nurses' pivotal role in oxygen administration is poorly understood. This study aimed to assess factors associated with oxygen administration to critically ill patients among nurses at Muhimbili National Hospital (MNH) in Dar es Salaam, Tanzania. A descriptive cross-sectional study was conducted among 208 nurses using a simple random technique to recruit respondents. Data were collected in May 2022 via a self-administered questionnaire, designed and tested by the authors. Mean knowledge and practice scores were used to categorize knowledge and practice as high or low respectively. The Chi-square test and multiple logistic regression analyses were performed to evaluate factors associated with knowledge and practice regarding oxygen administration. Statistical significance was determined at a p-value less than 0.05. Of the 208 respondents, 96(46.2%) and 78(37.5%) had low knowledge and low practices regarding oxygen administration, respectively. Receiving in-service training on oxygen administration (AOR: 3.515; p<0.001) was positively associated with knowledge of oxygen administration. None of the factors showed a statistically significant association with the practice of oxygen administration. A substantial proportion of nurses had inadequate knowledge and practices regarding oxygen administration. While none of the assessed factors were found to have a statistical association with practice on oxygen administration, it is important to note their clinical significance. Healthcare institutions can benefit from implementing regular in-service training programs to address these knowledge and skills gaps and ensure that nurses are well-prepared for proper oxygen administration. Additionally, ongoing monitoring and support are essential to help translate improved knowledge into effective clinical practices.

Protein supplementation delivered alone or in combination with presumptive azithromycin treatment for enteric pathogens did not improve linear growth in Bangladeshi infants: results of a cluster-randomized controlled trial.

Protein requirements established for healthy populations may be insufficient to support healthy growth in infants consuming largely cereal-based complementary foods and frequently exposed to enteric pathogens. To assess independent and combined effects of protein supplementation and antibiotic treatment on linear growth of infants from 6-12 months of age. We conducted a 2 x 4 factorial cluster-randomized trial in northwestern Bangladesh, allocating 566 clusters to masked azithromycin (10 mg·kg-1 * 3 d) or placebo at 6 and 9 months of age, and unmasked delivery of an egg white protein-rich blended food supplement (250 kcal; 10 g added protein), a rice-based isocaloric supplement, egg, or nutrition education from 6-12 months. We measured length at 6 and 12 months. For this cluster-level intention-to-treat analysis of the 2 x 2 antibiotic and protein interventions, we used multiple linear or log-binomial regression with generalized estimating equations to assess changes in length-for-age Z (LAZ) score and stunting (LAZ<-2), respectively. We enrolled 2055 infants (283 clusters) and included 1821 infants (281 clusters) with complete anthropometry data at 6 and 12 months in our analysis. There were no significant interactions between the protein and antibiotic interventions for any outcomes. Independently, protein supplement did not improve LAZ (β = 0.05; 95% CI: 0.00, 0.11; P = 0.07) or reduce stunting (prevalence ratio (PR) = 1.12; 95% CI: 0.85, 1.49; P = 0.41) compared to the isocaloric supplement. The antibiotic intervention had no effect on LAZ (β = -0.05; 95% CI: -0.11, 0.01; P = 0.09) or stunting (PR = 0.99; 95% CI: 0.75, 1.31; P = 0.96), relative to the placebo. Supplementation to increase intakes of high-quality protein, provided with or without presumptive treatment for enteric pathogens, did not improve linear growth from 6 to 12 months of age. This trial was registered at clinicaltrials.gov as NCT03683667. This trial was registered at clinicaltrials.gov as NCT03683667.

In vitro photodynamic therapy of Candida albicans, the cause of vulvovaginal candidiasis, is enhanced by Bacillus and Enterococcus probiotics.

Candida albicans is the primary cause of vulvovaginal candidiasis, a worldwide health concern for women. The use of supplemental methods, such as antimicrobial photodynamic therapy (aPDT) and probiotics, was promoted by the ineffectiveness of the existing antifungal drugs. This study examines the combined effects of probiotics (Bacillus and Enterococcus isolated from the fermented pickles) and PDT (using red laser (655 nm, 18 J/cm2) as a light source and methylene blue dye (30 mg/mL) as a photosensitizer) on the in vitro virulence activity of C. albicans including growth, biofilm formation, antifungal resistance, biofilm elimination, and biofilm dispersion. The probiotic strains demonstrated a higher resistance to PDT compared to the fungal cell. Bacillus and Enterococcus enhanced the antifungal effects of PDT on planktonic Candida cells in both pre-PDT and post-PDT interactions. The inhibition of biofilm formation by PDT was improved upon interaction with Bacillus (70%) and Enterococcus (58%). The eradication of Candida biofilm using PDT was increased after a combination with Bacillus (67%) and Enterococcus (46%). The nystatin resistance of the fungal biofilm following PDT treatment was decreased from (µg/ml) 25 to 6.25 due to the interaction with both probiotic strains. Fungal cell dispersion from the biofilm after PDT treatment diminished by 18% and 25% in the presence of Bacillus and Enterococcus strains. Galleria mellonella mortality was significantly changed following the PDT of the fungi/probiotic-injected larvae. This synergistic activity suggests the use of probiotics/PDT as a supplemental treatment for vulvovaginal candidiasis.

DYNAMICS OF CLINICAL INDICATORS OF HEALING POST-EXTRACTION WOUNDS AFTER REMOVAL OF MESIALLY INCLINED IMPACTED LOWER THIRD MOLARS

This article highlights changes in clinical indicators, including the depth of periodontal pockets, thickness of attached gums, and the condition of the lower second molar, during the postoperative period. The purpose of the study was to evaluate the clinical indicators of healing in post-extraction wounds following the removal of mesially inclined impacted lower third molars, using both a standard protocol and a protocol with supplemental treatment, in a comparative perspective. Subjects and Methods. The patients were divided into two groups: the main group, which followed the protocol with supplemental treatment, and the control group, which underwent the standard atypical tooth extraction protocol. The condition of the tissues around the post-extraction wound was assessed on the 1st, 2nd, 5th, 7th, and 30th days post-operation. Clinical indicators included the evaluation of the volume and topography of attached gums, depth of periodontal pockets, as well as functional and biomechanical indicators of the lower second molar. Results. The results of the study indicate that the use of the proposed protocol led to improvements in the condition of the attached gums and periodontal pockets, as well as a reduction in the mobility of the second molar. In the main group of patients, by the 30th day, the indicators of electric pulp testing (EPT) returned to physiological levels, demonstrating the effectiveness of the proposed surgical treatment method. The study has revealed that in the control group, the indicators of the volume and topography of attached gums decreased by an average of 20.0% of the initial volume by the 7th day, unlike the main group, where this indicator significantly decreased by an average of 15.0% from baseline values. It has been proven that on the 2nd day after the surgical intervention, an increase in the depth of periodontal pockets by up to 15% from the initial level was observed in 24 patients (80% of cases) in the main group, whereas in the control group, this was noted in 27 patients (90% of cases). Normalization of this indicator in the main group was noted by the 30th day while small changes persisted in 6 patients (20% of cases), as opposed to 16 patients (53.3% of cases) in the control group. Significant differences between the groups were determined from the analysis of second molar mobility and EPT. The absence of mobility of the second molar was found in 25 patients in the main group (83.3% of cases), compared to the control group where this indicator was observed in 70% of cases. Physiological electrical conductivity of the tooth remained below 5 units in 27 patients from the main group (90.0% of cases) by the 30th day, while in the control group it was found in 23 patients (69.0% of cases), validating the effectiveness of our modified protocol for the atypical removal of mesially inclined lower third molars. Conclusion. The implementation of an improved standardization table for clinical indicators to assess tissue condition after the removal of mesially inclined impacted lower third molars enhances postoperative monitoring of reparative processes, enables timely detection of potential complications, and supports the development of algorithms for their resolution.

Effects of supplementary light treatment on saffron: integrated physiological, metabolomic, and transcriptome analyses.

Saffron (Crocus sativus L.) is a perennial, bulbous flower whose stigma is one of the most valuable spices, herbal medicines, and dyes. Light is an essential environmental regulator of plant growth, development, and metabolism. With the popularization of customized light-emitting diode (LED) light sources in facility agriculture, accurate light control has become essential for regulating crop yield and quality. In this study, white, red, and blue LED lights were applied to extend the photoperiod at the start and end of the day during the indoor stage of saffron cultivation. We investigated saffron growth and flowering using non-target metabolomic and transcriptome analyses to determine the flux and accumulation of metabolites from the stigma under different light treatments. The results revealed that supplemental red and white lights both promoted dry mass accumulation in the stigma, with the optimal appearance achieved using white light. Supplemental white light promoted saffron flowering, whereas supplemental blue light delayed it. Supplemental blue light promoted crocin-1 and crocin-3 accumulation, whereas supplemental red light promoted crocin-2 accumulation. Expression analysis of key genes and their correlations with crocin-related metabolites may provide useful information for screening functional genes involved in crocin synthesis. This study provides useful information for future application of LED light to improve the planting technology, quality, and yield of saffron, and reveals underlying molecular information for the further research.

Determination of selenium speciation in the muscle, kidney, and liver from different animals treated with different selenium supplements by HPLC‐ICP‐MS

AbstractDietary selenium (Se) deficiency is recognized as a global problem, and exogenous Se supplementation can effectively enrich its levels in animal bodies. Offal tissues are equally important as meat in Se enrichment. Varying properties among Se species require information beyond total Se concentration to fully evaluate health risk/benefits. In the present study, the reliable inductively coupled plasma mass spectrometry (ICP‐MS) and HPLC‐ICP‐MS methods were optimized to analyze total Se content and Se speciation in the muscle and kidney of sheep, kidney and liver of pig, and liver of chicken after different Se supplementation treatments. The total Se contents in the liver and kidney were higher than in muscle. Five Se species were detected in the muscle, and selenourea was additionally detected in the liver and kidney. Sheep muscle and chicken liver mainly contained selenomethionine, and other tissues mainly contained selenocysteine. As the levels of selenomethionine or selenium‐enriched yeast increased in the feed, the proportion of selenomethionine in the sample increased, as well as the proportion of selenocysteine decreased, and almost no inorganic selenium was detected in all tissues. This study has provided insights for analyzing the Se enrichment patterns in tissues, which is significant for understanding the Se metabolism, animal health, and enriching the dietary Se supplementation for humans.

Overview of Acne, their Biochemical Relevance and Roles in Skin Health

Acne is a chronic inflammatory skin disorder that impacts both physical appearance and mental health in people of all ages. Niacinamide, or vitamin B3, has drawn interest recently as a potential supplementary or alternative treatment for acne because of its anti-inflammatory, antioxidant, and sebum-regulating qualities. This review's objective is to assess niacinamide's efficacy in treating acne by examining clinical research, its mode of action, and its safety profile. Several studies have shown that topical niacinamide can enhance skin barrier function, lessen inflammation, and lessen the severity of acne lesions without causing the irritation that more severe therapies do. Niacinamide is also a possible treatment for post-inflammatory hyperpigmentation because it has been demonstrated to improve skin repair. The data currently in favor of using niacinamide to treat acne is summarized in this review. Keywords: Acne vulgaris, Niacinamide, Nicotinamide, inflammation, treatment, acne lesions, hyperpigmentation.

Effects of Nutritional Support with a Leucine-Enriched Essential Amino Acid Supplement on Body Composition, Muscle Strength, and Physical Function in Stroke Patients Undergoing Rehabilitation.

Dietary protein intake can potentially influence renal function. This study aimed to elucidate the association between dietary protein supplementation and a decrease in the estimated glomerular filtration rate (eGFR) in Japanese stroke patients undergoing rehabilitation. From July 2017 to June 2021, 60 patients undergoing post-stroke rehabilitation were randomly assigned to a rehabilitation alone or rehabilitation nutrition group, which received 120 g Reha-Time Jelly® after each session. Both groups were followed up for 3 months. Serum nutritional markers (prealbumin and retinol-binding protein), muscle strength, body composition, renal function markers (eGFR based on creatinine [eGFR-Cr] and cystatin C [eGFR-Cys]), urinary protein-to-creatinine ratio (UPCR), and motor function (walking speed, 2-min walk distance, and chair stand test) were assessed at baseline and post-intervention. Of the 60 participants (mean age: 70.2 ± 10.0 years), 39 were men (65.0%) and 19 (31.7%) had chronic kidney disease. Initial eGFR-Cr and eGFR-Cys values were 70.5 ± 17.2 and 66.6 ± 14.8 mL/min/1.73 m2, respectively. After the intervention, the rehabilitation nutrition group demonstrated a significantly greater increase in body mass index (BMI) and a smaller decrease in bone mineral content than the rehabilitation alone group. However, no significant between-group differences were noted in serum marker levels or motor function, including grip strength and knee extensor strength, on the paralyzed and non-paralyzed sides. The change in chair stand test performance indicated a trend toward improvement in the rehabilitation nutrition group. No significant differences were observed in the changes in renal function. A 3-month nutritional supplementation intervention may help increase BMI, preserve bone mineral content, and support physical activity levels in patients undergoing post-stroke rehabilitation without negatively affecting renal function.

Nutritional management and autism spectrum disorder: A systematic review.

Autism spectrum disorder (ASD) presents unique challenges related to feeding and nutritional management. Children with ASD often experience feeding difficulties, including food selectivity, refusal, and gastrointestinal issues. Various interventions have been explored to address these challenges, including dietary modifications, vitamin supplementation, feeding therapy, and behavioral interventions. To provide a comprehensive overview of the current evidence on nutritional management in ASD. We examine the effectiveness of dietary interventions, vitamin supplements, feeding therapy, behavioral interventions, and mealtime practices in addressing the feeding challenges and nutritional needs of children with ASD. We systematically searched relevant literature up to June 2024, using databases such as PubMed, PsycINFO, and Scopus. Studies were included if they investigated dietary interventions, nutritional supplements, or behavioral strategies to improve feeding behaviors in children with ASD. We assessed the quality of the studies and synthesized findings on the impact of various interventions on feeding difficulties and nutritional outcomes. Data extraction focused on intervention types, study designs, participant characteristics, outcomes measured, and intervention effectiveness. The review identified 316 studies that met the inclusion criteria. The evidence indicates that while dietary interventions and nutritional supplements may offer benefits in managing specific symptoms or deficiencies, the effectiveness of these approaches varies. Feeding therapy and behavioral interventions, including gradual exposure and positive reinforcement, promise to improve food acceptance and mealtime behaviors. The findings also highlight the importance of creating supportive mealtime environments tailored to the sensory and behavioral needs of children with ASD. Nutritional management for children with ASD requires a multifaceted approach that includes dietary modifications, supplementation, feeding therapy, and behavioral strategies. The review underscores the need for personalized interventions and further research to refine treatment protocols and improve outcomes. Collaborative efforts among healthcare providers, educators, and families are essential to optimize this population's nutritional health and feeding practices. Enhancing our understanding of intervention sustainability and long-term outcomes is essential for optimizing care and improving the quality of life for children with ASD and their families.

Interaction between Vitamin D homeostasis, gut microbiota, and central precocious puberty.

Central precocious puberty (CPP) is an endocrine disease in children, characterized by rapid genital development and secondary sexual characteristics before the age of eight in girls and nine in boys. The premature activation of the hypothalamic-pituitary-gonadal axis (HPGA) limits the height of patients in adulthood and is associated with a higher risk of breast cancer. How to prevent and improve the prognosis of CPP is an important problem. Vitamin D receptor (VDR) is widely expressed in the reproductive system, participates in the synthesis and function of regulatory sex hormones, and affects the development and function of gonads. In addition, gut microbiota plays an important role in human health by mainly regulating metabolites, energy homeostasis, and hormone regulation. This review aims to clarify the effect of vitamin D deficiency on the occurrence and development of CPP and explore the role of gut microbiota in it. Although evidence on the interaction between vitamin D deficiency, gut microbiota, and sexual development remains limited, vitamin D supplementation and gut microbiota interventions offer a promising, non-invasive strategy for managing CPP.

Development of a riboflavin-responsive model of riboflavin transporter deficiency in zebrafish.

Riboflavin transporter deficiency (RTD) is a rare and progressive neurodegenerative disease resulting from the disruption of RFVT2- and RFVT3- mediated riboflavin transport caused by biallelic mutations in SLC52A2 and SLC52A3, respectively. The resulting impaired mitochondrial metabolism leads to sensorimotor neurodegeneration and symptoms including muscle weakness, respiratory difficulty, and sensorineural deafness. Although over 70% of patients with RTD improve following high-dose riboflavin supplementation, remaining patients either stabilise or continue to deteriorate. This may be due to the rapid excretion of central nervous system (CNS) riboflavin by organic anion transporter 3 (OAT-3), highlighting the need for alternative or supplemental RTD treatments. Probenecid is a promising therapeutic candidate for RTD due to its known inhibitory effect on OAT-3. Therefore, this study aimed to generate morpholino-mediated knockdowns of human SLC52A3 ortholog slc52a3 in zebrafish larvae for use in therapeutic screening of riboflavin and probenecid. Knockdown of slc52a3 resulted in an RTD-like phenotype indicative of altered neurodevelopment, hearing loss, and reduced mobility. This RTD-like phenotype overlaps with the phenotype of CRISPR/Cas9-mediated knockout of slc52a3 in zebrafish, is maintained following slc52a3 morpholino + p53 morpholino co-injection, and is rescued following slc52a3 morpholino + human SLC52A3 mRNA co-injection, indicating specificity of the knockdown. Riboflavin treatment alone ameliorates locomotor activity and hearing ability in slc52a3 morphants. Riboflavin and probenecid co-treatment provides an additional small benefit to hearing but not to locomotion. Our findings demonstrate that this model recapitulates both the RTD phenotype and the riboflavin-responsiveness of RTD patients, and possible therapeutic benefit conferred by probenecid warrants further investigation.

Oral supplementation with Nicotinamide Riboside treatment protects RGCs in DBA/2J mouse model.

The aim of this study was to test whether oral administration of nicotinamide riboside (NR), the nicotinamide adenine dinucleotide (NAD+) precursors, protect retina ganglion cells (RGCs) from neurodegeneration in DBA/2J (D2) mice, which is a widely used mouse model of age-related inherited glaucoma. Oral NR or NAM administration (NR low dose: 1150mg/kg; NR high dose: 4200mg/kg; NAM low dose group: 500mg/kg; NAM high dose: 2000mg/kg of body weight per day) essentially started when D2 mice were 4 or 9 months old and continued up to 12 months old. Control cohort identically received food/water without NAM or NR. Intraocular pressure (IOP) was measured every month until experiment completion. Pattern electroretinography (PERG) was recorded. Retinas were harvested for whole mount immunofluorescence staining with RGCs marker Brn3a and imaged by fluorescent confocal microscopy. Optic nerves were harvested for axon staining and quantification. Retinal NAD+ levels were enzymatically assayed. NR oral supplementary treatment started at 4 months old robustly increased retinal NAD+ levels in D2 mice (NRHigh vs. vehicle: 273.7±23.59% vs. 108.70±12.10%, p<0.001). In aged vehicle group (12 months old), there was significantly diminution of the P1 and N2 components of PERG response compare with naïve group (naïve vs. vehicle: P1: 7.82± 0.70uV vs 1.63± 0.17uV, p<0.0001; N2: -13.29± 0.83uV vs. -3.22± 0.27uV, p<0.0001; Kruskal-Wallis test with Dunn's multiple comparison test). NR treatment preserved aged D2 visual function when mice were 9 and 12 months old. In addition, long-term NR high dose treatment significantly protected against total RGCs loss and optic nerve atrophy (RGC: NRHigh vs. vehicle: 1412±62.00vs 475.2±94.68 cells/field, p<0.00001; axon numbers: NRHigh vs. vehicle: 23990±1159 vs 8573±1160, n=41-53, p<0.0001). Furthermore, long-term NR supplementation prevent iris depigmentation and delayed IOP elevation. NR oral supplementary treatment significantly preserved RGC and axon numbers, potentially preserves retinal function via elevated retinal NAD+ level in aged D2 mice. Interestingly, NR treatment also prevented iris atrophy, delayed IOP elevation associated with this glaucoma model. NR oral supplementation thus treated several aspects of murine pigment dispersion glaucoma. Given parallels between this model and glaucoma in human, out data indicate that NR is worth exploring as a therapeutic candidate in treatment of glaucoma.

Peiminine Enhances Doxorubicin Cytotoxicity and Downregulates hsa-miR-106a-5p and hsa -miR-181a-5p in Human Gastric Adenocarcinoma Cells

Background: Gastric cancer (GC) is a prevalent and deadly cancer worldwide. Chemotherapy is the primary treatment, but some patients use herbal remedies, such as Peiminine from Fritillaria walujewii, for palliative care. Cancer cells can affect the expression of noncoding RNAs, like microRNA, which can then influence the expression of genes. This research aims to study the effects of Peiminine on Doxorubicin cytotoxicity and detect the expression levels of hsa-miR-106a-5p and hsa-miR-181a-5p in AGS human gastric adenocarcinoma cells. Materials and Methods: AGS cells were cultured and treated with different concentrations of Peiminine. An MTT assay was performed to determine the concentration of Peiminine required to prohibit 50% cell growth (IC50) and the cell viability percentage of the AGS cell line. The percentage of AGS cell line apoptosis was determined using acridine orange (AO) and ethidium bromide (EtBr). Finally, molecular studies were conducted to compare hsa-miR-106a-5p and hsa-miR-181a-5p expression in the control and treated groups. Results: According to the study, Peiminine has been found to enhance the cytotoxicity of Doxorubicin, which reduces cell viability and increases apoptosis in the AGS cell line. Furthermore, the study also indicates that the AGS cell line treated with Peiminine shows lower expression of hsa -miR-106a-5p and hsa -miR-181a-5p compared to the control group that was not treated. Conclusion: Peiminine enhances Doxorubicin’s effectiveness, inhibits AGS cell line growth, and reduces miRNA expression. Further research is needed for potential use as a supplementary GC treatment.