RESOLUTION OF CALVARIAL HYPEROSTOSIS IN AFRICAN LION CUBS (PANTHERA LEO LEO) AFTER VITAMIN A SUPPLEMENTATION.

Two female (FL 1, FL 2) and one male (ML) 11-wk-old, intact, captive African lion cubs (Panthera leo leo) were presented with a history of mild vestibular signs. Initial serum vitamin A concentrations were low (140 nmol/L) for ML. Calvarial hyperostosis was confirmed using computed tomography (CT) of the head and cervical vertebrae in each cub. CT measurements were adapted in relation to the skull width. ML showed the most pronounced thickening of the tentorium cerebelli and occipital bone, represented by a tentorium cerebelli to skull width ratio (TCR) of 0.08 (FL 1: 0.06, FL 2: 0.05) and a basisphenoid to skull width ratio (BBR) of 0.07 (FL 1: 0.06, FL 2: 0.04). Magnetic resonance imaging (MRI) revealed cerebellar herniation and cervical intramedullary T2-weighted hyperintensity from C1, extending caudally for at least two cervical vertebrae in all cubs. Treatment was initiated with subcutaneous vitamin A supplementation and feeding of whole carcasses. Improvement in ataxia was noticed 3 wk later. Follow-up CT and MRI examinations were performed in ML after 3 and 8 mon. The affected bones appeared slightly less thickened and TCR and BBR had decreased to 0.05 after 3 mon. The cerebellum remained mildly herniated, accompanied by amelioration of cervical T2w hyperintensities. After 8 mon, evaluation and diagnostic imaging revealed further improvement regarding the neurologic status and measurements (TCR 0.05, BBR 0.04) despite persistence of a subtle cerebellar herniation. In conclusion, bone remodeling and improvement in clinical signs may be achievable in young lion cubs presented with calvarial hyperostosis and may be attributable to high-dose vitamin A supplementation.

Feasibility of delivering vitamin A supplementation (VAS) and deworming through routine community health services in Siaya County, Kenya: A cross-sectional study.

Vitamin A deficiency and soil-transmitted helminth infection are serious public health problems in Kenya. The coverage of vitamin A supplementation and deworming medication (VASD) provided through mass campaigns is generally high, yet with a cost that is not sustainable, while coverage offered through routine health services is low. Alternative strategies are needed that achieve the recommended coverage of >80% of children twice annually and can be managed by health systems with limited resources. We undertook a study from September to December 2021 to compare the feasibility and coverage of VASD locally delivered by community health volunteers (CHV) ("intervention arm") to that achieved by the bi-annual Malezi Bora campaign event ("control arm"). This comparative cross-sectional study was conducted in sub-counties of Siaya County using both qualitative and quantitative methods. VASD were offered through the CHS in Alego Usonga and through Malezi Bora in Bondo Sub-County. Coverage was assessed by a post-event coverage survey among caregivers of children aged 6-59 months (n = 307 intervention; n = 318 control). Key informant interviews were conducted with n = 43 personnel across both modalities, and 10 focus group discussions were conducted with caregivers of children aged 6-59 months to explore knowledge, attitudes and perceptions of the two strategies. VAS coverage by CHV was 90.6% [95% CI: 87.3-93.9] compared to 70.4% [95% CI: 65.4-75.4] through the Malezi Bora, while deworming coverage was 73.9% [95% CI: 69.0-78.7] and 54.7% [95% CI: 49.2-60.2], respectively. With sufficient training and oversight, CHV can achieve superior coverage to campaigns.

Vitamin A ameliorates valproic acid-induced autism-like symptoms in developing zebrafish larvae by attenuating oxidative stress and apoptosis.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by social deficits and repetitive/stereotyped behaviors. Prenatal exposure to valproic acid (VPA) has been reported to induce ASD-like symptoms in human and rodents. However, the etiology and pathogenesis of ASD have not been well elucidated. This study aimed to explore the mechanisms underlying VPA-induced ASD-like behaviors using zebrafish model and investigated whether vitamin A could prevent VPA-induced neurotoxicity. Here, zebrafish embryos were exposed to 0, 25 and 50 µM VPA from 4 to 96 h post fertilization (hpf) and the neurotoxicity was assessed. Our results showed that VPA affected the normal development of zebrafish larvae and induced ASD-like behaviors, including reduced locomotor activity, decreased distance near conspecifics, impaired social interaction and repetitive swimming behaviors. Exposure to VPA decreased the GFP signal in transgenic HuC:egfp zebrafish according to the negative effect of VPA on the expression of neurodevelopmental genes. In addition, VPA enhanced oxidative stress by promoting the production of reactive oxygen species (ROS) and hydrogen peroxide (H2O2) and inhibiting the activity of superoxide dismutase, then triggered apoptosis by upregulation of apoptotic genes. These adverse outcomes were mitigated by vitamin A, suggesting that vitamin A rescued VPA-induced ASD-like symptoms by inhibiting oxidative stress and apoptosis. Overall, this study identified vitamin A as a promising strategy for future therapeutic regulator of VPA-induced ASD-like behaviors.

The role and impact of abnormal vitamin levels in autism spectrum disorders.

The prevalence of autism spectrum disorder (ASD), a neurodevelopmental disorder with a predominance of social behavioral disorders, has increased dramatically in various countries in recent decades. The interplay between genetic and environmental factors is believed to underlie ASD pathogenesis. Recent analyses have shown that abnormal vitamin levels in early life are associated with an increased risk of autism. As essential substances for growth and development, vitamins have been shown to have significant benefits for the nervous and immune systems. However, it is unknown whether certain vitamin types influence the emergence or manifestation of ASD symptoms. Several studies have focused on vitamin levels in children with autism, and neurotypical children have provided different insights into the types of vitamins and their intake. Here, we review the mechanisms and significance of several vitamins (A, B, C, D, E, and K) that are closely associated with the development of ASD in order to prevent, mitigate, and treat ASD. Efforts have been made to discover and develop new indicators for nutritional assessment of children with ASD to play a greater role in the early detection of ASD and therapeutic remission after diagnosis.

Exploring the therapeutic efficacy of crocetin in oncology: an evidence-based review.

With cancer being a leading cause of death globally, there is an urgent need to improve therapeutic strategies and identify effective chemotherapeutics. This study aims to highlight the potential of crocetin, a natural product derived from certain plants, as an anticancer agent. It was  conducted an extensive review of the existing literature to gather and analyze the most recent data on the chemical properties of crocetin and its observed effects in various in vitro and in vivo studies. The study  particularly focused on studies that examined crocetin's impact on cell cycle dynamics, apoptosis, caspases and antioxidant enzyme levels, tumor angiogenesis, inflammation, and overall tumor growth. Crocetin exhibited diverse anti-tumorigenic activities including inhibition of tumor cell proliferation, apoptosis induction, angiogenesis suppression, and potentiation of chemotherapy. Multiple cellular and molecular pathways such as the PI3K/Akt, MAPK and NF-κB were modulated by it. Crocetin demonstrates promising anti-cancer properties and offers potential as an adjunctive or alternative therapy in oncology. More large-scale, rigorously designed clinical trials are needed to establish therapeutic protocols and ascertain the comprehensive benefits and safety profile of crocetin in diverse cancer types.

Effect of vitamin A on maternal, fetal, and neonatal outcomes: An overview of deficiency, excessive intake, and intake recommendations.

Vitamin A imbalance during pregnancy and lactation is a global public health concern with potentially negative consequences for fetuses and neonates. Inadequate vitamin A intake during this critical period can lead to anemia, weakened immune function, night blindness, and increased susceptibility to infections. Conversely, excessive intake of vitamin A can result in birth defects, hypercalcemia, and psychiatric symptoms. This review aims to identify risk factors contributing to vitamin A deficiency in pregnant women and its impact on maternal, fetal, and neonatal outcomes. It also examines the effects of high-dose vitamin A supplementation during pregnancy on offspring health. By analyzing existing literature and recommendations, the review emphasizes the significance of vitamin A in the development of various body systems and organs. It provides a comprehensive overview of the effects of vitamin A during pregnancy and lactation, encompassing deficiencies, excessive intake, and supplementation guidelines. The need for further research in this field is highlighted. In conclusion, maintaining a balanced vitamin A status is crucial during pregnancy to promote better outcomes for fetuses and newborns. Effective monitoring and intervention strategies are essential to address vitamin A deficiency and excess in pregnant women, thereby improving fetal and neonatal health.

Treatment patterns of systemic drug use in Japanese patients with plaque psoriasis: A retrospective chart review.

Plaque psoriasis (PsO) is a chronic immune-mediated inflammatory disease with skin lesions accompanied by an inflammation-related comorbidity risk. The development of various oral drugs and biologics for PsO has provided increasing systemic treatment options for patients with PsO, and the guidance regarding the use of biologics and PsO treatment schemes are widespread in Japan. However, no comprehensive guidelines regarding systemic drug use are available, and the current treatment patterns of systemic drugs for PsO in Japan remain unclear. We conducted a retrospective chart review to clarify the current treatment patterns of systemic drugs for PsO. We enrolled 114 patients who started systemic drugs for PsO between January 2017 and December 2020 at four institutes, with a mean follow-up of 37.2 months. The mean disease duration was 7.8 (standard deviation 9.5) years at the systemic drug initiation. Of all the patients, 78.1% started with oral drugs (phosphodiesterase [PDE] 4 inhibitors 56.1%. calcineurin inhibitors 14.0%. vitamin A derivatives 7.9%), whereas 21.9% started with biologics (interleukin [IL]-17 inhibitors 9.6%. tumor necrosis factor inhibitors 7.0%. IL-23 inhibitors 3.5%. IL-12/23 inhibitors 1.8%). Oral drugs had shorter drug persistence than biologics: the 12-month persistence of the oral drugs vitamin A derivative, calcineurin inhibitor, and PDE4 inhibitor, was 35.5%, 25.8%, and 60.1%, respectively, compared with that of the biologics IL-23 and IL-17 inhibitors, which was 85.6% and 84.7%, respectively. During the study period, the incidence of treatment changes was 59.1/100 patient-years. Lack of efficacy was the most common reason for treatment changes from monotherapy (34.1%). This retrospective medical chart review allowed us to understand the real-world, long-term treatment patterns of systemic drugs for PsO and the relationships between the reasons for treatment changes and subsequent treatment selection, indicating that there is still room for improvement in the appropriate use of systemic drugs for PsO in Japan.

Effects of oral isotretinoin treatment for acne vulgaris patients on anger responses and the relationship with temperament.

OBJECTIVE: Isotretinoin is the only medication against all the factors involved in acne vulgaris pathogenesis. The aim of our study was to verify whether patients with acne vulgaris receiving isotretinoin therapy exhibit elevated anger levels and to observe the correlation between age, temperament traits, and anger. METHODS: The study group comprised a sum of 100 cases, involving 50 individuals with acne vulgaris-required high-dose retinol therapy and 50 controls who did not start any medication. RESULTS: Our study showed that anger levels increased with drug use. A positive correlation between cyclothymic temperament, the anxiety-related behavior subdimension, and the introvert and passive-aggressive subdimension of interpersonal anger reactions has been recognized. In addition, a positive one was observed between hyperthymic temperament and the introvert subdimension, which is one of the anger-related thoughts and interpersonal anger reactions. CONCLUSION: This study elucidates anger dimensions such as anger-related thoughts, behaviors, and reactions in individuals who received retinol treatment for acne vulgaris. In addition to anger and its dimensions, temperament was also investigated. Although several studies have investigated the relationship between acne vulgaris and psychiatric symptoms, to the best of our knowledge, no research has been reported in the English-language literature regarding the relationship between anger dimensions and temperament after retinol treatment that might make our study an original and valuable contribution to the literature.

Feasibility and safety of integrating mass drug administration for helminth control with seasonal malaria chemoprevention among Senegalese children: a randomized controlled, observer-blind trial.

BACKGROUND: The overlap in the epidemiology of malaria and helminths has been identified as a potential area to exploit for the development of an integrated control strategy that may help to achieve elimination of malaria and helminths. A randomized, controlled, observer-blind trial was conducted to assess the feasibility and safety of combining mass drug administration (MDA) for schistosomiasis and soil transmitted helminths (STH) with seasonal malaria chemoprevention (SMC) among children living in Senegal. METHODS: Female and male children aged 1-14 years were randomized 1:1:1, to receive Vitamin A and Zinc on Day 0, followed by SMC drugs (sulfadoxine-pyrimethamine and amodiaquine) on Days 1-3 (control group); or praziquantel and Vitamin A on Day 0, followed by SMC drugs on Days 1-3 (treatment group 1); or albendazole and praziquantel on Day 0, followed by SMC drugs on Days 1-3 (treatment group 2). Safety assessment was performed by collecting adverse events from all children for six subsequent days following administration of the study drugs. Pre- and post-intervention, blood samples were collected for determination of haemoglobin concentration, malaria microscopy, and PCR assays. Stool samples were analyzed using Kato-Katz, Merthiolate-iodine-formalin and PCR methods. Urine filtration, PCR and circulating cathodic antigen tests were also performed. RESULTS: From 9 to 22 June 2022, 627 children aged 1-14 years were randomized into the three groups described above. Mild, transient vomiting was observed in 12.6% (26/206) of children in treatment group 2, in 10.6% (22/207) in group 1, and in 4.2% (9/214) in the control group (p = 0.005). Pre-intervention, the geometric mean value of Plasmodium falciparum parasite density was highest among children who received albendazole, praziquantel with SMC drugs. Post-intervention, the parasite density was highest among children who received SMC drugs only. Children who received praziquantel and SMC drugs had a lower risk of developing severe anaemia than their counterparts who received SMC drugs alone (OR = 0.81, 95% CI 0.13-5.00, p = 0.63). CONCLUSIONS: Integration of MDA for helminths with SMC drugs was safe and feasible among Senegalese children. These findings support further evaluation of the integrated control model. TRIAL REGISTRATION: The study is registered at Clinical Trial.gov NCT05354258.

[25 Years from Di Bella affair: what ethical lessons does it leave us?] / 25 Años del asunto Di Bella: ¿qué enseñanzas éticas nos deja?

Twenty-five years ago, in 1998, the Italian Parliament approved to implement clinical trials in patients with advanced cancer to know the efficacy of an alternative cancer treatment that associated hormones, vitamins and, occasionally, chemotherapy proposed by Professor Luigi Di Bella. It was the answer to people demanding Public Health assume the cost of this therapy. Although parallel phase II trials in various tumors demonstrated the lack of activity, some professionals have continued to use this method since then and have published apparently promising results a few various scientific journals. This real example raises three interesting ethical scenarios. The first one is the ethics of alternative treatments proposed by medical professionals or from the academic field. In these cases, the difficulty in differentiating between hypothesis and real efficacy. This problem impacts on patients and relatives' expectations who must face a potentially fatal disease with little or no hope of a cure with traditional treatments. The second scenario is the design and good practice in the development of clinical trials, which was also the subject of debate in relation to the Di Bella method. And the last one, the ethics of scientific publications. Di Bella's followers published since 2000 12 papers with limited quality on series of patients treated with his method, the majority in a pay-per-publication journal of which Giuseppe Di Bella, son of Professor Di Bella, is included in the board of editors.

Enhanced effect of seasonal malaria chemoprevention when coupled with nutrients supplementation for preventing malaria in children under 5 years old in Burkina Faso: a randomized open label trial.

BACKGROUND: In rural African settings, most of the children under the coverage of Seasonal Malaria Chemoprevention (SMC) are also undernourished at the time of SMC delivery, justifying the need for packaging malarial and nutritional interventions. This study aimed at assessing the impact of SMC by coupling the intervention with nutrients supplementation for preventing malaria in children less than 5 years old in Burkina Faso. METHODS: A randomized trial was carried out between July 2020 and June 2021 in the health district of Nanoro, Burkina Faso. Children (n = 1059) under SMC coverage were randomly assigned to one of the three study arms SMC + Vitamin A (SMC-A, n = 353) or SMC + Vitamin A + Zinc (SMC-AZc, n = 353) or SMC + Vitamin A + PlumpyDoz(tm) (SMC-APd, n = 353)-a medium quantity-lipid-based nutrient supplement (MQ-LNS). Children were followed up for one year that included an active follow-up period of 6 months with scheduled monthly home visits followed by 6 months passive follow-up. At each visit, capillary blood sample was collected for malaria diagnosis by rapid diagnosis test (RDT). RESULTS: Adding nutritional supplements to SMC had an effect on the incidence of malaria. A reduction of 23% (adjusted IRR = 0.77 (95%CI 0.61-0.97) in the odds of having uncomplicated malaria in SMC-APd arm but not with SMC-AZc arm adjusted IRR = 0.82 (95%CI 0.65-1.04) compare to control arm was observed. A reduction of 52%, adjusted IRR = 0.48 (95%CI 0.23-0.98) in the odds of having severe malaria was observed in SMC-APd arm compared to control arm. Besides the effect on malaria, this combined strategy had an effect on all-cause morbidity. More specifically, a reduction of morbidity odds of 24%, adjusted IRR = 0.76 (95%CI 0.60-0.94) in SMC-APd arm compared to control arm was observed. Unlike clinical episodes, no effect of nutrient supplementation on cross sectional asymptomatic infections was observed. CONCLUSION: Adding nutritional supplements to SMC significantly increases the impact of this intervention for preventing children from malaria and other childhood infections. TRIAL REGISTRATION: NCT04238845.

Joint analysis of the metabolomics and transcriptomics uncovers the dysregulated network and develops the diagnostic model of high-risk neuroblastoma.

High-risk neuroblastoma (HR-NB) has a significantly lower survival rate compared to low- and intermediate-risk NB (LIR-NB) due to the lack of risk classification diagnostic models and effective therapeutic targets. The present study aims to characterize the differences between neuroblastomas with different risks through transcriptomic and metabolomic, and establish an early diagnostic model for risk classification of neuroblastoma.Plasma samples from 58 HR-NB and 38 LIR-NB patients were used for metabolomics analysis. Meanwhile, NB tissue samples from 32 HR-NB and 23 LIR-NB patients were used for transcriptomics analysis. In particular, integrative metabolomics and transcriptomic analysis was performed between HR-NB and LIR-NB. A total of 44 metabolites (P < 0.05 and fold change > 1.5) were altered, including 12 that increased and 32 that decreased in HR-NB. A total of 1,408 mRNAs (P < 0.05 and |log2(fold change)|> 1) showed significantly altered in HR-NB, of which 1,116 were upregulated and 292 were downregulated. Joint analysis of both omic data identified 4 aberrant pathways (P < 0.05 and impact ≥ 0.5) consisting of glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism. Importantly, a HR-NB risk classification diagnostic model was developed using plasma circulating-free S100A9, CDK2, and UNC5D, with an area under receiver operating characteristic curve of 0.837 where the sensitivity and specificity in the validation set were both 80.0%. This study presents a novel pioneering study demonstrating the metabolomics and transcriptomics profiles of HR-NB. The glycerolipid metabolism, retinol metabolism, arginine biosynthesis and linoleic acid metabolism were altered in HR-NB. The risk classification diagnostic model based on S100A9, CDK2, and UNC5D can be clinically used for HR-NB risk classification.

Modulatory role of vitamins A, B3, C, D, and E on skin health, immunity, microbiome, and diseases.

Disruption of the skin barrier and immunity has been associated with several skin diseases, namely atopic dermatitis (AD), psoriasis, and acne. Resident and non-resident immune cells and the barrier system of the skin are integral to innate immunity. Recent advances in understanding skin microbiota have opened the scope of further understanding the various communications between these microbiota and skin immune cells. Vitamins, being one of the important micronutrients, have been reported to exert antioxidant, anti-inflammatory, and anti-microbial effects. The immunomodulatory action of vitamins can halt the progression of skin diseases, and thus, understanding the immuno-pharmacology of these vitamins, especially for skin diseases can pave the way for their therapeutic potential. At the same time, molecular and cellular markers modulated with these vitamins and their derivatives need to be explored. The present review is focused on significant vitamins (vitamins A, B3, C, D, and E) consumed as nutritional supplements to discuss the outcomes and scope of studies related to skin immunity, health, and diseases.

Insights into vitamin A in bladder cancer, lack of attention to gut microbiota?

Vitamin A has long been associated with bladder cancer, and many exogenous vitamin A supplements, vitamin A derivatives, and synthetic drugs have been investigated over the years. However, the effectiveness of these strategies in clinical practice has not met expectations, and they have not been widely adopted. Recent medical research on intestinal flora has revealed that bladder cancer patients exhibit reduced serum vitamin A levels and an imbalance of gut microbiota. In light of the close relationship between gut microbiota and vitamin A, one can speculate that a complex regulatory mechanism exists between the two in the development and occurrence of bladder cancer. As such, further exploration of their interaction in bladder cancer may help guide the use of vitamin A for preventive purposes. During the course of this review, attention is paid to the influence of intestinal microbiota on the vitamin A metabolism and the RA signaling pathway, as well as the mutual promotion relationships between them in the prevention of bladder cancer, In addition, it emphasizes the importance of intestinal microbiota for bladder cancer prevention and treatment.

Vutrisiran: A Review in Polyneuropathy of Hereditary Transthyretin-Mediated Amyloidosis.

Silencing the transthyretin (TTR) gene is an effective strategy in the treatment of hereditary transthyretin-mediated (hATTR) amyloidosis. Vutrisiran (Amvuttra®), an RNA interference (RNAi) therapeutic targeting TTR mRNA, is approved in the USA and EU for the treatment of adults with polyneuropathy of hATTR amyloidosis. N-acetylgalactosamine conjugation and enhanced stabilisation chemistry are utilised to target vutrisiran to the liver and increase stability, respectively, allowing for subcutaneous administration once every 3 months. In a pivotal phase 3 study in patients with hATTR amyloidosis with polyneuropathy, subcutaneous vutrisiran 25 mg every 3 months significantly reduced neuropathy impairment versus external placebo. Vutrisiran was also associated with significant improvements in neuropathy-specific quality of life, gait speed, nutritional status and disability scores. Vutrisiran was generally well tolerated; the only common adverse events to occur at a greater incidence than with external placebo were pain in extremity and arthralgia. Vutrisiran reduces serum vitamin A levels and vitamin A supplementation is recommended. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, which has the potential advantage of infrequent subcutaneous dosage.

Hereditary transthyretin-mediated (hATTR) amyloidosis is a progressive and disabling disease caused by variants in the transthyretin (TTR) gene, which cause destabilisation and misfolding of the TTR protein. Deposition of misfolded TTR protein (amyloid) around nerves causes a range of neuropathic symptoms. Vutrisiran (Amvuttra^®) silences the TTR gene via RNA interference (RNAi). Vutrisiran, administered subcutaneously once every 3 months, is approved in the USA and EU for the treatment of polyneuropathy of hATTR amyloidosis in adults. In a phase 3 study in patients with hATTR amyloidosis with polyneuropathy, vutrisiran significantly reduced neuropathy impairment and improved other disease-related outcomes versus external placebo. Vutrisiran was generally well tolerated, with most adverse events being mild or moderate in severity. As vutrisiran decreases vitamin A levels, patients undergoing vutrisiran treatment should supplement with vitamin A. In conclusion, vutrisiran is an efficacious and generally well-tolerated alternative option for the treatment of polyneuropathy of hATTR amyloidosis, with a convenient dosage regimen.

A novel mouse model of heart failure with preserved ejection fraction after chronic kidney disease induced by retinol through JAK/STAT pathway.

Heart failure is the leading cardiovascular comorbidity in chronic kidney disease (CKD) patients. Among the types of heart failure according to ejection fraction, heart failure with preserved ejection fraction (HFpEF) is the most common type of heart failure in CKD patients. However, the specific animal model of HFpEF afer CKD is currently missing. In this study, we determined the heart failure characteristics and dynamic progression in CKD mice. Based on these features, we established the practical HFpEF after CKD mouse model using 5/6 subtotal nephrectomy and retinol administration. Active apoptosis, impaired calcium handling, an imbalance between eNOS and oxidative stress and engaged endoplasmic reticulum stress were observed in our model. RNSseq revealed distinct gene expression patterns between HFpEF after CKD and metabolic induced-HFpEF. Furthermore, we revealed the potential mechanism of the pro-HFpEF effect of retinol. Serum accumulation of retinol in CKD prompts myocardial hypertrophy and fibrosis by activating JAK2 and phosphorylating STAT5. Finally, using small molecule inhibitor AC-4-130, we found STAT5 phosphorylation inhibitor may be a potential intervention target for HFpEF after CKD. In conclusion, we provide a novel animal model and a potential drug target for HFpEF intervention in CKD.

Home Gardening of Yellow Cassava and Orange Maize for the Prevention of Nutritional Blindness in Children: An Economic Evaluation and Value of Information Analysis.

OBJECTIVES: Vitamin A deficiency is the leading cause of childhood blindness worldwide, affecting mostly Sub-Saharan Africa. We aimed to predict the cost-effectiveness of home gardening (HG) of yellow cassava and orange maize to prevent nutritional blindness in children below 5 years and to assess the likely value of obtaining additional information in reducing uncertainty surrounding its cost-effectiveness. METHODS: We developed a Markov model and carried out probabilistic sensitivity analysis with a value of information analysis. We costed resources from a societal perspective and outcomes were measured in disability-adjusted life years (DALYs). RESULTS: HG was estimated to cost an additional Intl$395.00 per DALY averted, with a 72.27% likelihood of being cost-effective at a threshold of Intl$2800 per DALY. The expected value of information was estimated to be Intl$29 843.50 for 1 child or Intl$925 billion for 31 million Nigerian children affected by the decision. Further research is only worthwhile for 1 parameter (relative risk of low serum retinol; expected value of perfect parameter information Intl$29 854.53 per child and Intl$925 billion for 31 million children). CONCLUSION: HG of yellow cassava and orange maize is expected to be highly cost-effective in preventing nutritional blindness in Nigerian children. Worthwhile further research includes a cost analysis of the intervention and a high-quality randomized trial to assess the effectiveness of HG on serum retinol levels in young children.

Clinical and histologic findings after use of a novel combined retinol, tripeptide, and glaucine containing cream in the treatment of photo-aged skin.

BACKGROUND: Neck skin is thinner and has a more delicate dermal layer than facial skin. The studied product was specifically formulated for the neck combining a hydrating delivery system with a trifunctional corrective technology composed of 0.2% pure retinol, 2.5% tripeptide concentrate, and 5.0% glaucine complex to help improvement in signs of aging. OBJECTIVES: To evaluate cosmetic and histologic changes 3 months after treatment using immunostains for Type I collagen, Type III collagen, and glycosaminoglycan (GAGS). In addition, overall clinical improvement in photoaged skin was measured by both Griffith's photonumeric photoaging scale, photographic improvement, and questionnaires. METHODS: This study was an open-label, blinded clinical trial evaluating a combined retinol, tripeptide, and glaucine containing cream in the treatment of photo-aged skin. The study enrolled a total of 20 healthy male or female subjects, who applied the product for 3 months to their face and neck. RESULTS: Clinical as well histologic changes were consistent with improvement in all 20 subjects. CONCLUSION: Use of a combined retinol, tripeptide, and glaucine containing cream led to both clinical and histologic improvement of phototoaging.

Nutritional peripheral neuropathies.

Nutritional peripheral neuropathies are a global problem, heavily influenced by geopolitical, cultural and socioeconomic factors. Peripheral neuropathy occurs most frequently secondary to B-vitamin deficiencies, which is suspected to increase in years to come due to the popularity of vegan and vegetarian diets and increased use of bariatric surgery.This review will focus on the common B-vitamins for which a causal link to peripheral neuropathy is more established (vitamins B1, B2, B6, B9 and B12). We will review the historical human and animal data on which much of the clinical descriptions of vitamin deficiencies are based and summarise current available tools for accurately diagnosing a nutritional deficiency. We will also review recently described genetic diseases due to pathogenic variants in genes involved in B-vitamin metabolism that have helped to inform the phenotypes and potential causality of certain B-vitamins in peripheral neuropathy (B2 and B9).Endemic outbreaks of peripheral neuropathy over the last two centuries have been linked to food shortages and nutritional deficiency. These include outbreaks in Jamaican sugar plantation workers in the nineteenth century (Strachan's syndrome), World War two prisoners of war, Cuban endemic neuropathy and also Tanzanian endemic optic neuropathy, which remains a significant public health burden today. An improved understanding of lack of which vitamins cause peripheral neuropathy and how to identify specific deficiencies may lead to prevention of significant and irreversible disability in vulnerable populations.

Pharmacological GLUT3 salvage augments the efficacy of vitamin C-induced TET2 restoration in acute myeloid leukemia.

Vitamin C has been demonstrated to regulate hematopoietic stem cell frequencies and leukemogenesis by augmenting and restoring Ten-Eleven Translocation-2 (TET2) function, potentially acting as a promising adjunctive therapeutic agent for leukemia. However, glucose transporter 3 (GLUT3) deficiency in acute myeloid leukemia (AML) impedes vitamin C uptake and abolishes the clinical benefit of vitamin C. In this study, we aimed to investigate the therapeutic value of GLUT3 restoration in AML. In vitro GLUT3 restoration was conducted with the transduction of GLUT3-overexpressing lentivirus or the pharmacological salvage with 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR) treatment to OCI-AML3, a naturally GLUT3-deficient AML cell line. The effects of GLUT3 salvage were further confirmed in patient-derived primary AML cells. Upregulation of GLUT3 expression made AML cells successfully augment TET2 activity and enhanced the vitamin C-induced anti-leukemic effect. Pharmacological GLUT3 salvage has the potential to overcome GLUT3 deficiency in AML and improves the antileukemic effect of vitamin C treatments.