Impact of supplementation with iron-folic acid (IFA) and vitamin D3 compared with IFA alone on haemoglobin levels in elderly people with mild-to-moderate anaemia: protocol for the double-blind, randomised, placebo-controlled Iron and vitamin D trial in Elderly Anemia (IDEA).

INTRODUCTION: Anaemia in the elderly is often difficult to treat with iron supplementation alone as prevalence of anaemia of chronic disease (ACD) alone or mixed with iron-deficiency anaemia (IDA) is high in this age group. Hepcidin remains high in ACD, preventing utilisation of iron for heme synthesis. Vitamin D3 has shown hepcidin suppression activity in both in vitro and in vivo studies. As there is no study assessing the effect of iron-folic acid (IFA) with vitamin D3 on haemoglobin levels in the elderly in India, we want to conduct this study to estimate the impact of supplementation of a therapeutic package of IFA and vitamin D3 on haemoglobin levels in the elderly with mild-to-moderate anaemia in comparison with IFA only. The study will also assess the impact of the proposed intervention on ferritin, hepcidin, 25-hydroxyvitamin D, C reactive protein (CRP) and parathyroid hormone (PTH) levels. METHODS AND ANALYSIS: This study is a community-based, double-blind, placebo-controlled, randomised trial. The study will be done in the Kalyani municipality area. Individuals aged ≥60 years with mild-to-moderate anaemia and normal vitamin D3 levels will be randomised into the intervention (IFA and vitamin D3 supplementation) group or the control group (IFA and olive oil as placebo). All medications will be self-administered. Follow-up will be done on a weekly basis for 12 weeks. The calculated sample size is 150 in each arm. Block randomisation will be done. The primary outcome is change in haemoglobin levels from baseline to 12 weeks. Secondary outcome is change in serum ferritin, 25-hydroxyvitamin D, hepcidin, CRP and PTH levels from baseline to 12 weeks. ETHICS AND DISSEMINATION: Ethical approval from the Institutional Ethics Committee of All India Institute of Medical Sciences Kalyani has been obtained (IEC/AIIMS/Kalyani/Meeting/2022/03). Written informed consent will be obtained from each study participant. The trial results will be reported through publication in a reputable journal and disseminated through health talks within the communities. TRIAL REGISTRATION NUMBER: CTRI/2022/05/042775. PROTOCOL VERSION: Version 1.0.

Haem iron versus ferrous iron salts to treat iron deficiency anaemia in Gambian children: protocol for randomised controlled trial {1}.

BACKGROUND: The World Health Organization recommends universal iron supplementation for children aged 6-23 months in countries where anaemia is seen in over 40% of the population. Conventional ferrous salts have low efficacy due to low oral absorption in children with inflammation. Haem iron is more bioavailable, and its absorption may not be decreased by inflammation. This study aims to compare daily supplementation with haem iron versus ferrous sulphate on haemoglobin concentration and serum ferritin concentration after 12 weeks of supplementation. METHODS: This will be a two-arm, randomised controlled trial. Gambian children aged 6-12 months with anaemia will be recruited within a predefined geographical area and recruited by trained field workers. Eligible participants will be individually randomised using a 1:1 ratio within permuted blocks to daily supplementation for 12 weeks with either 10.0 mg of elemental iron as haem or ferrous sulphate. Safety outcomes such as diarrhoea and infection-related adverse events will be assessed daily by the clinical team (see Bah et al. Additional file 4_Adverse event eCRF). Linear regression will be used to analyse continuous outcomes, with log transformation to normalise residuals as needed. Binary outcomes will be analysed by binomial regression or logistic regression, Primary analysis will be by modified intention-to-treat (i.e., those randomised and who ingested at least one supplement dose of iron), with multiple imputations to replace missing data. Effect estimates will be adjusted for baseline covariates (C-reactive protein, alpha-1-acid glycoprotein, haemoglobin, ferritin, soluble transferrin receptor). DISCUSSION: This study will determine if therapeutic supplementation with haem iron is more efficacious than with conventional ferrous sulphate in enhancing haemoglobin and ferritin concentrations in anaemic children aged 6-12 months. TRIAL REGISTRATION: Pan African Clinical Trial Registry PACTR202210523178727.

Mineral supplementation for very preterm infants fed fortified human milk.

OBJECTIVES: The safety and feasibility of human milk fortification with bovine colostrum (BC) were investigated in very preterm infants (FortiColos trial, NCT03537365). The BC product contained lower calcium, phosphate, and iron levels compared to the conventional fortifier (CF). We tested whether fortification with BC plus extra phosphate was sufficient to support the infants' mineral status assessed by blood biochemistry. METHODS: In a randomised controlled trial (FortiColos, NCT03537365), mineral status was compared after fortification with BC versus CF. Blood calcium, phosphate, and haemoglobin were determined before and up to 3 weeks after the start of fortification (at the mean age of 8-9 days). The maximum supplemental doses of calcium, phosphate, and iron given were retrieved from patient medical records. Results were adjusted for gestational age, birth weight, and enteral nutrition with the mother's own milk and/or donor human milk. RESULTS: Blood values of calcium, phosphate, and haemoglobin were similar between groups. Infants in both groups required supplementation with calcium and phosphate, but infants fed BC required higher maximum doses of phosphate and calcium (p < 0.05) to maintain acceptable blood values. Regardless of fortification groups, the most immature (<29 weeks of gestation) and small for gestational age infants showed a higher risk for requiring additional phosphate (odds ratio [OR]: 3.9, p < 0.001; OR: 2.14, p = 0.07, respectively). CONCLUSIONS: The use of BC as a fortifier for human milk requires additional phosphate and calcium relative to a CF. Regardless of the fortification product, the most immature and small infants require additional mineral supplementation.

[Evaluation of the efficacy and safety of intravenous infusion of ferric derisomaltose in the treatment of iron deficiency anemia: a single-center retrospective analysis].

Objective: To investigate the clinical efficacy and safety of ferric derisomaltose injection versus iron sucrose injection in the treatment of iron deficiency anemia (IDA) . Methods: A total of 120 patients with iron deficiency anemia admitted from June 2021 to March 2023 were given intravenous iron supplementation with ferric derisomaltose to assess the efficacy and safety of hemoglobin (HGB) elevation before and after treatment. Simultaneously, the clinical effects of iron supplementation with iron sucrose were compared to those of inpatient patients during the same period. Results: Baseline values were comparable in both groups. Within 12 weeks of treatment, the elevated HGB level in the ferric derisomaltose group was higher than that of the iron sucrose group, with a statistical difference at all time points, and the proportion of HGB increased over 20 g/L in the patients treated for 4 weeks was higher (98.7%, 75.9% ). During the treatment with ferric derisomaltose and iron sucrose, the proportion of mild adverse reactions in the ferric derisomaltose group was slightly lower than that of the iron sucrose group, and neither group experienced any serious adverse reactions. The patients responded well to the infusion treatment, with no reports of pain or pigmentation at the injection site. Conclusion: The treatment of IDA patients with ferric derisomaltose has a satisfactory curative effect, with the advantages of rapidity, accuracy, and safety. Therefore, it is worthy of widespread clinical use.

Weight loss induced by a hypocaloric diet with or without fish oil supplementation re-established iron and omega-3 fatty acid homeostasis in middle-aged women with obesity: A post-hoc analysis of a randomized controlled trial.

OBJECTIVE: Middle-aged women with obesity are at increased risk of iron overload and iron disorder is known to disrupt n-3 polyunsaturated fatty acid homeostasis. We evaluated relationships between pretreatment hemoglobin and n-3 polyunsaturated fatty acid levels, and tested whether pretreatment hemoglobin contributed to inter-individual variability in weight loss with special focus on changes in body weight, iron and n-3 polyunsaturated fatty acid profiles. STUDY DESIGN: 117 middle and older aged women with obesity and more than two metabolic abnormalities were randomized to a 12-week hypocaloric diet without or with fish oil supplementation. Blood iron biomarker and erythrocyte membrane phospholipid profiles were evaluated. MAIN OUTCOME: The absolute change from baseline to week 12 in serum iron and erythrocyte n-3 polyunsaturated fatty acid levels according to pretreatment hemoglobin tertiles and fish oil supplementation. RESULTS: A Pearson correlation analysis showed that pretreatment hemoglobin levels were negatively correlated with linoleic acid (r = -0.231), α-linoleic acid (r = -0.279), and n-3 polyunsaturated fatty acid (r = -0.217) (all p < 0.05). Dietary weight loss markedly enhanced erythrocyte membrane lipids of linoleic acid, α-linoleic acid, and n-6 and n-3 polyunsaturated fatty acid only in those women with the highest pretreatment hemoglobin levels (tertile 3) (all p < 0.05). Fish oil supplementation increased bioavailable iron in women with moderate pretreatment hemoglobin levels (tertile 2) (p < 0.05) and, to a lesser extent, prevented a reduction in circulating iron in those with the lowest hemoglobin levels (tertile 1). CONCLUSION: Dietary weight loss is an effective treatment program to manage obesity-related iron and n-3 polyunsaturated fatty acid disorders, particularly for middle-aged women with obesity and iron overload.

Prevalence of Micronutrient Deficiencies in Preoperative Bariatric Patients in a New Zealand Tertiary Centre.

PURPOSE: A potential complication of bariatric surgery is development of nutritional deficiencies. Study aims were to assess prevalence of micronutrient deficiencies in preoperative bariatric patients and to examine for ethnic differences. METHODS: Retrospective analysis of 573 patients that underwent bariatric surgery at Counties Manukau District Health Board was carried out. Mean preoperative levels of albumin, calcium, phosphate, folate, vitamin B12, vitamin D, magnesium, haemoglobin, haematocrit, mean cell volume, mean cell haemoglobin, ferritin, iron, and transferrin were calculated. Chi square, fisher exact test, and multiple logistic regression was used to assess for differences in prevalence of micronutrient deficiencies across ethnicities. RESULTS: The most common micronutrient deficiency was vitamin D (30.85%). There were statistically significant differences in vitamin D deficiency across ethnicities (p < 0.0001). Asians had the highest prevalence of vitamin D deficiency (60%), followed by Pacifica (44.57%), and Maori (31.68%). Asians were more likely to have vitamin D deficiency compared to NZ/Other Europeans (OR = 14.93, p < 0.001). Vitamin D deficiency was associated with higher BMI (OR = 1.05, p = 0.008). The second most common deficiency was iron (21.1%). Asians had the highest prevalence of iron deficiency (44%), followed by Maori (27.95%), and Pacifica (19.57%) (p = 0.0064). Compared to NZ/Other Europeans, Asians (OR = 4.26) and Maori (OR = 1.78) were more likely to be iron deficient (p = 0.004). Female gender was associated with iron deficiency (OR = 2.12, p = 0.007). CONCLUSION: Vitamin D and iron are the most common micronutrient deficiencies among preoperative bariatric patients in this cohort and ethnic differences were seen. There may be a role for preoperative supplementation in these at-risk ethnic groups.

Relationship between hemoglobin and grip strength in older adults: the ActiFE study.

INTRODUCTION: Although anemia is associated with low muscle strength, hemoglobin has been rarely studied considering ferritin. AIM: To analyze the association between hemoglobin and grip strength in community-dwelling older adults. METHODS: We used data from a German cohort of adults ≥ 65 years, excluding those with CRP > 10 mg/L or taking iron supplements. Grip strength (kg) was measured using a Jamar dynamometer. Analysis was performed using multiple linear regression, adjusted for established confounders. Due to interaction, age-stratified (< 80, 80 +), further sex-stratified analysis in those < 80 years old and ferritin-stratified in men < 80 years were performed. RESULTS: In total, 1294 participants were included in this analysis (mean age 75.5 years, 549 (42.3%) women, 910 (70.3%) < 80 years). On average, hemoglobin and grip strength were 14.9 g/dL and 41.3 kg for men, 13.9 g/dL and 25.1 kg for women. Hemoglobin was significantly positively associated with grip strength only among women < 80 years (ß 0.923 [95% CI 0.196, 1.650]). For men < 80 years, the association was significant when ferritin was ≥ 300 µg/L (ß 2.028 [95% CI 0.910, 3.146]). No association was detected among those participants 80 + . DISCUSSION AND CONCLUSIONS: Our data show an association between hemoglobin and grip strength only in women < 80 years old. For men < 80 years, the association was only significant with ferritin levels ≥ 300 µg/L. Considering the decreasing levels of hemoglobin and grip strength and the high prevalence of iron deficiency in older adults further analyses investigating this relationship with more iron specific parameters such as transferrin saturation are warranted.

Iron Status and Risk of Heart Disease, Stroke, and Diabetes: A Mendelian Randomization Study in European Adults.

BACKGROUND: The relevance of iron status biomarkers for coronary artery disease (CAD), heart failure (HF), ischemic stroke (IS), and type 2 diabetes (T2D) is uncertain. We compared the observational and Mendelian randomization (MR) analyses of iron status biomarkers and hemoglobin with these diseases. METHODS AND RESULTS: Observational analyses of hemoglobin were compared with genetically predicted hemoglobin with cardiovascular diseases and diabetes in the UK Biobank. Iron biomarkers included transferrin saturation, serum iron, ferritin, and total iron binding capacity. MR analyses assessed associations with CAD (CARDIOGRAMplusC4D [Coronary Artery Disease Genome Wide Replication and Meta-Analysis Plus The Coronary Artery Disease Genetics], n=181 522 cases), HF (HERMES [Heart Failure Molecular Epidemiology for Therapeutic Targets), n=115 150 cases), IS (GIGASTROKE, n=62 100 cases), and T2D (DIAMANTE [Diabetes Meta-Analysis of Trans-Ethnic Association Studies], n=80 154 cases) genome-wide consortia. Observational analyses demonstrated J-shaped associations of hemoglobin with CAD, HF, IS, and T2D. In contrast, MR analyses demonstrated linear positive associations of higher genetically predicted hemoglobin levels with 8% higher risk per 1 SD higher hemoglobin for CAD, 10% to 13% for diabetes, but not with IS or HF in UK Biobank. Bidirectional MR analyses confirmed the causal relevance of iron biomarkers for hemoglobin. Further MR analyses in global consortia demonstrated modest protective effects of iron biomarkers for CAD (7%-14% lower risk for 1 SD higher levels of iron biomarkers), adverse effects for T2D, but no associations with IS or HF. CONCLUSIONS: Higher levels of iron biomarkers were protective for CAD, had adverse effects on T2D, but had no effects on IS or HF. Randomized trials are now required to assess effects of iron supplements on risk of CAD in high-risk older people.

Compliance With NCCN Guidelines for Evaluation and Treatment of Anemia Among Patients With Solid Tumors.

BACKGROUND: NCCN Guidelines for Hematopoietic Growth Factors recommend evaluation and treatment of anemia in patients with cancer. However, a paucity of data exists regarding compliance with these recommendations. METHODS: A retrospective cohort study was performed of patients diagnosed with any solid tumor at Vanderbilt University Medical Center from 2008 to 2017. Tumor registry-confirmed cancer cases were identified by ICD-O codes using the Synthetic Derivative database. Anemia was defined as hemoglobin (Hgb) level ≤11 g/dL and graded according to CTCAE version 5.0. Absolute, functional, and possible functional iron deficiency were defined based on NCCN Guidelines. RESULTS: A total of 25,018 patients met inclusion criteria. Median age was 60 years. The most common malignancies were respiratory tract, prostate, and nonprostate urologic (11% each). Among 8,695 patients with Hgb levels available prior to diagnosis, 1,484 (17%) were noted to be anemic proximal to diagnosis. Of the 25,018 patients, 11,019 (44%) were anemic within 6 months of diagnosis. Of these patients, 4,686 (43%) had grade 2 (moderate) anemia and 9,623 (87%) had normocytic anemia. Patients with retroperitoneal/peritoneal cancers had the highest prevalence of anemia (83/110; 75%). A total of 4,125 (37%) underwent any evaluation of their anemia, of whom 1,742 (16%) had iron studies performed and 1,528 (14%) had vitamin B12 or folate studies performed. Fewer than half of patients with anemia received treatment (n=4,318; 39%), including blood transfusion (n=3,528; 32%), oral iron supplementation (n=1,279; 12%), or intravenous iron supplementation (n=97; 1%). Anemia treatment was significantly more frequent as the grade of anemia increased (any treatment among grade 1/mild: 12%; grade 2/moderate: 31%; grade 3/severe: 77%; χ2 [2, n=11,019]=3,020.6; P<.001). Patients with penile and testicular cancers had the highest prevalence of anemia evaluation (n=57; 79%). CONCLUSIONS: Anemia is common in patients with solid tumors; yet, compliance with NCCN Guidelines for evaluation and treatment of anemia remains low. There are opportunities to improve compliance with guidelines across the spectrum of cancer care.

The effect of UNIMMAP multiple micronutrient supplements versus iron-folic acid and placebo in anemia reduction among women of reproductive age in Kebribeyah Woreda, Somali Regional State, Ethiopia: a study protocol for a community-based individual RCT.

BACKGROUND: Women of reproductive age (WRA) in developing countries are often at risk of micronutrient deficiencies due to inadequate intakes and excessive losses. OBJECTIVE: The purpose of this trial is to assess the effectiveness of United Nations International Multiple Micronutrient Antenatal Preparation-Multiple Micronutrient Supplements (UNIMMAP-MMS) versus iron-folic acid (IFA) among WRA in reducing anemia. METHODS: Three parallel groups of WRA will participate in a community-based, individually randomized, double-blinded, placebo-controlled superiority trial. After consent, the sample of 375 mildly or moderately anemic women based on hemoglobin by Hemocue will be randomly assigned across two interventions and one control arm. Trial participants in intervention arms will receive UNIMMAP-MMS or IFA while those in the control arm will receive placebos twice a week for 17 weeks. The primary outcome will be a change in mean hemoglobin (Hb) concentrations. Outcome assessors and study participants will be blinded to the type of supplements and study arm. DISCUSSION: The World Health Organization (WHO) added UNIMMAP-MMS to its essential medicine lists in 2021 but recommended rigorous study. Several factors in addition to inadequate intakes of iron and folic acid contribute to the high prevalence of anemia among WRA in the Somali region. The findings of this study will provide evidence on the effect of UNIMMAP-MMS and IFA on Hb concentrations and anemia prevalence among anemic WRA. TRIAL REGISTRATION: ClinicalTrials.gov NCT05682261. Registered on January 12, 2023.

Comparative Analysis of Psychophysiological Responses in Fibromyalgia Patients: Evaluating Neuromodulation Alone, Neuromodulation Combined with Virtual Reality, and Exercise Interventions.

BACKGROUND AND OBJECTIVES: Fibromyalgia, a chronic condition, manifests as widespread musculoskeletal pain, fatigue, sleep disturbances, autonomic and cognitive dysfunction, hypersensitivity to stimuli, and various somatic and psychiatric symptoms. This study, a controlled and randomized experiment, aimed to evaluate and compare the immediate effects of different treatments on fibromyalgia patients. MATERIALS AND METHODS: The treatments included the EXOPULSE Mollii suit, a combination of the EXOPULSE Mollii suit with a virtual reality (VR) protocol, and a physical exercise regimen. A cohort of 89 female fibromyalgia patients was randomly assigned to one of four groups: Control (n = 20), Suit only (n = 22), Suit combined with VR (n = 21), and Exercise (n = 26). RESULTS: This study found notable differences across the groups in several key parameters. In the Control group, significant changes were observed in Forced Expiratory Volume (FEV 1/FEV 6), the Numeric Rating Scale (NRS) for pain, Pressure Pain Threshold (PPT) at the epicondyle, cortical arousal levels, the 10 m up-and-go test, and in all measured variables related to temperature and muscle oxygenation. For the group using the suit alone, there were significant differences noted in the NRS, the chair stand test, palm temperature, and all muscle oxygenation parameters. The Suit + VR group showed significant changes in the NRS, PPT at the knee, handgrip strength test, the 10 m up-and-go test, one-leg balance test with the right leg, muscle oxygen saturation (SmO2), deoxygenated hemoglobin (HHb), and oxygenated hemoglobin (O2Hb). Finally, the Exercise group exhibited significant differences in FEV 1/FEV 6, chest perimeter difference, NRS, PPT at both the epicondyle and knee, cortical arousal, the chair stand test, the 10-m up-and-go test, and in SmO2, HHb, and O2Hb levels. CONCLUSIONS: combining neuromodulation with VR and targeted exercise regimens can effectively alleviate fibromyalgia symptoms, offering promising avenues for non-pharmacological management.

Exploration of the Clinical Effect of Different Autotransfusion Methods on Patients With Femoral Shaft Fracture Surgery.

OBJECTIVE: To explore the clinical effect of predeposit, salvage, and hemodilution autotransfusion on patients with femoral shaft fracture (FSF) surgery. METHODS: Selected patients with FSF were randomly divided into three groups: intraoperative blood salvage autotransfusion, preoperative hemodilution autohemotransfusion, and predeposit autotransfusion. Five days after the operation, the body temperature, heart rate, blood platelet (PLT), and hemoglobin (Hb) of patients were determined. The concentrations of EPO and GM-CSF in the three groups were calculated by ELISA. The content of CD14+ monocytes was calculated by FCM assay. The growth time and condition of the patient's callus were determined at the 30th, 45th, and 60th day after operation. Cox regression analysis was used to analyze the correlation between EPO, GM-CSF, CD14+ mononuclear content, callus growth, and autotransfusion methods. RESULTS: There were no statistically significant differences in body temperature and heart rate between the three groups (p > 0.05). PLT and Hb in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The concentrations of EPO and GM-CSF in the Predeposit group were markedly increased compared with that in the Salvage and Hemodilution groups. The content of CD14+ monocytes in the Predeposit group was significantly higher than that in the Salvage and Hemodilution groups. Predeposit autotransfusion promotes callus growth more quickly. CONCLUSION: Predeposit autotransfusion promoted the recovery of patients with FSF after the operation more quickly than salvage autotransfusion and hemodilution autotransfusion.

Rujifang inhibits triple-negative breast cancer growth via the PI3K/AKT pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Rujifang (RJF) constitutes a traditional Chinese medicinal compound extensively employed in the management of triple-negative breast cancer (TNBC). However, information regarding its potential active ingredients, antitumor effects, safety, and mechanism of action remains unreported. AIM OF THE STUDY: To investigate the efficacy and safety of RJF in the context of TNBC. MATERIALS AND METHODS: We employed the ultra high-performance liquid chromatography-electrospray four-pole time-of-flight mass spectrometry technique (UPLC/Q-TOF-MS/MS) to scrutinize the chemical constituents of RJF. Subcutaneously transplanted tumor models were utilized to assess the impact of RJF on TNBC in vivo. Thirty female BLAB/c mice were randomly divided into five groups: the model group, cyclophosphamide group, and RJF high-dose, medium-dose, and low-dose groups. A total of 1 × 106 4T1 cells were subcutaneously injected into the right shoulder of mice, and they were administered treatments for a span of 28 days. We conducted evaluations on blood parameters, encompassing white blood cell count (WBC), red blood cell count (RBC), hemoglobin (HGB), platelet count (PLT), neutrophils, lymphocytes, and monocytes, as well as hepatorenal indicators including alkaline phosphatase (ALP), glutamate oxaloacetate transaminase (GOT), glutamate pyruvate transaminase (GPT), albumin, and creatinine (CRE) to gauge the safety of RJF. Ki67 and TUNEL were detected via immunohistochemistry and immunofluorescence, respectively. We prepared RJF drug-containing serum for TNBC cell lines and assessed the in vitro inhibitory effect of RJF on tumor cell growth through the CCK8 assay and cell cycle analysis. RT-PCR was employed to detect the mRNA expression of cyclin-dependent kinase and cyclin-dependent kinase inhibitors in tumor tissues, and Western blot was carried out to ascertain the expression of cyclin and pathway-related proteins. RESULTS: 100 compounds were identified in RJF, which consisted of 3 flavonoids, 24 glycosides, 18 alkaloids, 3 amino acids, 8 phenylpropanoids, 6 terpenes, 20 organic acids, and 18 other compounds. In animal experiments, both CTX and RJF exhibited substantial antitumor effects. RJF led to an increase in the number of neutrophils in peripheral blood, with no significant impact on other hematological indices. In contrast, CTX reduced red blood cell count, hemoglobin levels, and white blood cell count, while increasing platelet count. RJF exhibited no discernible influence on hepatorenal function, whereas Cyclophosphamide (CTX) decreased ALP, GOT, and GPT levels. Both CTX and RJF reduced the expression of Ki67 and heightened the occurrence of apoptosis in tumor tissue. RJF drug-containing serum hindered the viability of 4T1 and MD-MBA-231 cells in a time and concentration-dependent manner. In cell cycle experiments, RJF diminished the proportion of G2 phase cells and arrested the cell cycle at the S phase. RT-PCR analysis indicated that RJF down-regulated the mRNA expression of CDK2 and CDK4, while up-regulating that of P21 and P27 in tumor tissue. The trends in CDKs and CDKIs protein expression mirrored those of mRNA expression. Moreover, the PI3K/AKT pathway displayed downregulation in the tumor tissue of mice treated with RJF. CONCLUSION: RJF demonstrates effectiveness and safety in the context of TNBC. It exerts anti-tumor effects by arresting the cell cycle at the S phase through the PI3K-AKT pathway.

Iron status in piglets at three days of age and at weaning and possible seasonal effects on the blood haemoglobin levels in a Swedish outdoor pig-producing farm.

BACKGROUND: Piglets are born with limited stores of iron, and with an increasing number of live-born piglets, there may be a risk that the sows cannot provide enough iron to their offspring. The iron content in soil may not meet the demands of today's piglet, born and reared in an outdoor setting. The study aimed to describe the blood haemoglobin (Hb) levels in pigs reared outdoors and to determine whether piglets have higher Hb levels at weaning when an iron supplement is administered intramuscularly at three days of age, as compared to pigs not given an iron supplement. The seasonal variation in Hb-levels was also to be investigated. The Hb concentration was analysed with a HemoCue 201 + Hb photometer. RESULTS: In total 56 litters (399 piglets) were included in the study and sampled at three days of age, while 378 piglets were sampled at weaning. The mean Hb level at three days of age was 91 g/L (48-154 g/L). In total 47% of the piglets had Hb levels < 90 g/L at three days of age. The mean Hb level at weaning was 127 g/L (76-176 g/L), with a lower level (122 g/L) in the group given the iron supplement than in the group not given an iron supplement (132 g/L). Only 1% of the piglets had Hb levels lower than 90 g/L at weaning. Results indicative of a seasonal effect on Hb levels at three days of age was demonstrated. Piglets born in spring had significantly lower Hb levels, and piglets born in autumn had significantly higher Hb levels. No seasonal effect could be demonstrated for Hb levels at day 33. CONCLUSIONS: The results indicate that the natural uptake from the environment was sufficient, but that there was a seasonal effect on the Hb levels at three days of age. This indicates that there might be a need for different routines regarding iron supplementation in outdoor reared piglets depending on the climate and season.

Status of vitamins and minerals in children with screening-identified celiac disease: A case-control study.

OBJECTIVES: Micronutrient deficiencies characterize classical "late-diagnosed" celiac disease (CeD). This study aimed to identify the prevalence of micronutrient deficiencies among children with "early-diagnosed" screening-identified CeD to determine the clinical value of routine testing for deficiencies in those patients. METHODS: A case-control study was conducted on screening-identified CeD patients diagnosed during a mass screening study (84 patients, mean age 11.3 ± 2.6 years). The controls (443 children, mean age 10.8 ± 2.5 years) were negative for celiac disease serological screening. Hemoglobin, serum levels of iron, ferritin, folate, vitamin B12, vitamin A, vitamin E, 25-OH vitamin D, zinc, and selenium were measured. RESULTS: The mean serum levels of hemoglobin, iron, ferritin, vitamin D, zinc, copper, and selenium were significantly lower in CeD patients than in healthy controls (hemoglobin 12.56 vs. 13.02 g/dL [p = 0.04]; iron 10.61 vs. 17.6 µmol/L [p < 0.001], ferritin 25.7 vs. 48.3 µg/L [p < 0.001], vitamin D 29.1 vs. 37.5 nmol/L, zinc 11.9 vs. 21.7 µmol/L, copper 18.9 vs. 32.5 µmol/L, selenium 1.04 vs. 1.36 µmol/L; p < 0.001). Patients with celiac and severe intestinal damage (Marsh IIIb and IIIc) had significantly lower serum ferritin and vitamin A levels than patients with mild intestinal damage (Marsh II and IIIa) (ferritin 15 vs. 22 µg/L, p < 0.025; vitamin A 0.85 vs. 1.35 µmol/L, p = 0.007). CONCLUSION: Micronutrient deficiencies are still detectable in "early-diagnosed" screening-identified CeD cases, a clinically relevant result that strongly supports efforts for screening and early diagnosis of CeD.

Riesgos y beneficios de la profilaxis con sulfato ferroso en lactantes nacidos a término con niveles de hemoglobina y ferremia desconocidos / Risks and benefits of iron supplementation in full-term infants with unknown hemoglobin and ferritin levels

La seguridad y eficacia de los programas de suplementación con hierro a lactantes, está actualmente en discusión. El objetivo de esta revisión fue identificar estudios sobre riesgos y beneficios de la suplementación con hierro profiláctico en lactantes menores de un año, nacidos a término, con niveles de hemoglobina (Hb) y ferremia desconocidos. Se realizó una búsqueda en Pubmed y Cochrane, identificando 3 revisiones sistemáticas y metaanálisis. Estos estudios arrojaron resultados que indican mejoras en los niveles séricos de hierro y hemoglobina como resultado de la suplementación con hierro. Sin embargo, no se observó un beneficio significativo en el desarrollo cognitivo de los lactantes. Los efectos adversos más reportados son los gastrointestinales, efectos en el crecimiento (menor ganancia de talla y peso) y menor absorción de zinc. En resumen, la evidencia en cuanto a la profilaxis con hierro en lactantes es limitada, lo que nos lleva a recomendar un seguimiento cercano de los lactantes que reciben suplementos de hierro, con el objetivo de detectar posibles eventos adversos. Es fundamental evaluar cuidadosamente los riesgos y beneficios de esta intervención antes de su implementación (AU)

The safety and efficacy of iron supplementation programs for infants are currently under discussion. The objective of this review was to identify studies on the risks and benefits of prophylactic iron supplementation in infants under one year of age, born at term, with unknown hemoglobin (Hb) and serum iron levels. The search was conducted on Pubmed and Cochrane, identifying three systematic reviews and meta-analyses. The results indicate improvements in serum iron and hemoglobin levels as a result of iron supplementation. However, a significant benefit in infant cognitive development was not observed. The most reported adverse effects were gastrointestinal, effects on growth (reduced height and weight gain), and reduced zinc absorption. In summary, the evidence regarding iron prophylaxis in infants is limited, leading us to recommend close monitoring of infants receiving iron supplements to detect potential adverse events. It is crucial to carefully assess the risks and benefits of this intervention before implementation (AU)

Effects of Oral Iron Supplementation on Blood Iron Status in Athletes: A Systematic Review, Meta-Analysis and Meta-Regression of Randomized Controlled Trials.

BACKGROUND: Iron deficiency in athletes is initially treated with a nutritional intervention. If negative iron balance persists, oral iron supplementation (OIS) can be used. Despite the recent proposal for a refinement of treatment strategies for iron-deficient athletes, there is no general consensus regarding the actual efficiency, dosage, or optimal regimen of OIS. OBJECTIVE: The aim of this meta-analysis was to evaluate to what extent OIS affects blood iron parameters and physical performance in healthy adult athletes. METHODS: PubMed, Web of Science, PEDro, CINAHL, SPORTDiscus, and Cochrane were searched from inception to 2 November 2022. Articles were eligible if they satisfied the following criteria: recruited subjects were healthy, adult and physically active individuals, who used exclusively OIS, irrespective of sex and sports discipline. EXCLUSION CRITERIA: simultaneous supplementation with iron and any other micronutrient(s), intravenous iron supplementation or recent exposure to altitude acclimatisation. The methodological quality of included studies was assessed with the PEDro scale, the completeness of intervention reporting with the TIDieR scale, while the GRADE scale was used for quality of evidence synthesis. The present study was prospectively registered in PROSPERO online registry (ID: CRD42022330230). RESULTS: From 638 articles identified through the search, 13 studies (n = 449) were included in the quantitative synthesis. When compared to the control group, the results demonstrated that OIS increases serum ferritin (standardized mean difference (SMD) = 1.27, 95% CI 0.44-2.10, p = 0.006), whereas blood haemoglobin (SMD = 1.31, 95% CI - 0.29 to 2.93, p = 0.099), serum transferrin receptor concentration (SMD = - 0.74, 95% CI - 1.89 to 0.41, p = 0.133), and transferrin saturation (SMD = 0.69, 95% CI - 0.84 to 2.22, p = 0.330) remained unaltered. Following OIS, a trend of small positive effect on VO2max (SMD = 0.49, 95% CI - 0.09 to 1.07, p = 0.086) was observed in young healthy athletes. The quality of evidence for all outcomes ranged from moderate to low. CONCLUSIONS: Increase in serum ferritin concentration after OIS was evident in subjects with initial pre-supplementation serum ferritin concentration ≤ 12 µg/l, while only minimal, if any effect, was observed in subjects with higher pre-supplementation serum ferritin concentration. The doses of OIS, that induced a beneficial effect on hematological parameters differed from 16 to 100 mg of elementary iron daily, over the period between 6 and 8 weeks. Shorter supplementation protocols have been shown to be ineffective.

Risk Factors for Thromboembolic Events in Patients With Dialysis-Dependent CKD: Pooled Analysis of Four Global Roxadustat Phase 3 Trials.

INTRODUCTION: Risk factors for thromboembolic events in patients with dialysis-dependent chronic kidney disease (CKD) receiving roxadustat are unknown. Iron deficiency has been reported as a risk factor for thrombosis in the general population. METHODS: Thromboembolic events with onset before and after week 12 in patients receiving roxadustat were evaluated in this pooled analysis of four global phase 3 trials, PYRENEES, SIERRAS, HIMALAYAS, and ROCKIES. Baseline risk factors for thromboembolic events were investigated by Cox regression analyses. Nested case-control analyses with matched pairs of case-control data explored the relationship between thromboembolic events and last known laboratory parameters before event onset. RESULTS: Of 2354 patients, 1026 thromboembolic events were observed in 568 patients. Baseline risk factors found included hemodialysis (vs peritoneal dialysis), advanced age (≥ 65 years), Black race, high high-sensitivity C-reactive protein, and history of thromboembolism, cardiovascular disease, or diabetes. Univariate case-control analyses revealed that high hemoglobin rate of rise (≥ 0.5 g/dL/week; odds ratio [OR] 2.09; 95% confidence interval [CI] 0.98-4.46) showed a trend towards increased risk of thromboembolic events before week 12, and high rate of hemoglobin decline was associated with events after week 12 (< - 0.5 g/dL/week; OR 3.73; 95% CI 1.68-8.27) as compared to stable hemoglobin levels (≥ - 0.1 to < 0.1 g/dL/week). Multivariate case-control analyses showed that low last known hemoglobin level (< 10 g/dL: adjusted OR 1.91; 95% CI 1.04-3.50; vs ≥ 12 g/dL) and low last known transferrin saturation (TSAT < 10%: adjusted OR 3.78; 95% CI 1.71-8.39; vs ≥ 30%) before event onset were associated with events after week 12. In patients with last known TSAT < 30%, higher roxadustat dose was associated with thromboembolic events; however, no association was observed in those with TSAT ≥ 30%. CONCLUSIONS: Among various risk factors for thromboembolic events, it is reasonable to avoid a rapid increase and decline in hemoglobin levels as well as ensure TSAT ≥ 30%, rather than increasing the roxadustat dose. Graphical Abstract available for this article. TRIAL REGISTRATION: NCT02278341, NCT02273726, NCT02052310, NCT02174731.

Roxadustat is an oral treatment for patients with anemia, or low hemoglobin levels, due to chronic kidney disease. Thromboembolic events are caused by a blood clot blocking blood vessels, and they have occurred in clinical trials of roxadustat. This analysis evaluated risk factors for thromboembolic events in patients receiving roxadustat to treat anemia of chronic kidney disease who are on dialysis. Two different statistical approaches were used to investigate risk factors for thromboembolic events that occurred before and after 12 weeks of roxadustat treatment. We found that rapid improvement of anemia after starting roxadustat treatment may be associated with an increased risk of thromboembolic events occurring in the first 12 weeks of treatment. In contrast, severe anemia or worsening of anemia was associated with an increased risk of thromboembolic events after week 12. Low iron levels in the blood or greater decline of available iron in the blood from baseline were also detected as risk factors for the events after week 12, suggesting that iron supplementation is important in patients who are iron-deficient. Moreover, thromboembolic events were also associated with older age (≥ 65 years), Black race, high levels of inflammation, and having had a previous thromboembolic event or having a history of cardiovascular disease or diabetes. Some risk factors, such as iron status and hemoglobin levels, can be changed after beginning roxadustat treatment and should be monitored and modified, as needed.

Development of novel polymer haemoglobin based particles as an antioxidant, antibacterial and an oxygen carrier agents.

This innovative work aims to develop highly biocompatible and degradable nanoparticles by encapsulating haemoglobin (Hb) within poly-ε-caprolactone for novel biomedical applications. We used a modified double emulsion solvent evaporation method to fabricate the particles. A Scanning electron microscope (SEM) characterized them for surface morphology. Fourier Transform Infrared Spectroscopy (FTIR) and Ultraviolet-visible spectroscopies (UV-visible) elucidated preserved chemical and biological structure of encapsulated haemoglobin. The airproof equilibrium apparatus obtained the oxygen-carrying capacity and P50 values. The DPPH assay assessed free radical scavenging potential. The antibacterial properties were observed using four different bacterial strains by disk diffusion method. The MTT assay investigates the cytotoxic effects on mouse fibroblast cultured cell lines (L-929). The MTT assay showed that nanoparticles have no toxicity over large concentrations. The well-preserved structure of Hb within particles, no toxicity, high oxygen affinity, P50 value, and IC50 values open the area of new research, which may be used as artificial oxygen carriers, antioxidant, and antibacterial agents, potential therapeutic agents as well as drug carrier particles to treat the cancerous cells. The novelty of this work is the antioxidant and antibacterial properties of developed nanoparticles are not been reported yet. Results showed that the prepared particles have strong antioxidant and antibacterial potential.

The iron status of rural Nigerian women in the second and third trimesters of pregnancy: implications for the iron endowment and subsequent dietary iron needs of their babies.

INTRODUCTION: The aim of the study was to determine the iron status of rural-dwelling pregnant Nigerian women in the second and third trimesters, and to predict their risk of giving birth to babies with suboptimal iron endowment. METHODS: This was a prospective cohort study conducted between April and August 2021. A total of 174 consecutive and consenting pregnant rural dwellers, who met the inclusion criteria, were recruited by convenience sampling from the antenatal clinic of a public hospital in Nsukka, a semirural town in south-east Nigeria. The study participants were aged 21-40 years, and their iron status was determined by measuring blood haemoglobin (Hb) and serum ferritin (SF) concentration. Hb concentration was determined by the cyanmethemoglobin method and the SF concentration was determined by enzyme immunoassay method. RESULTS: Almost half (47.7%) of the participants had Hb concentrations below 11 g/dL, while about two out of every five (40.8%) had SF concentrations less than 15 µg/L. The prevalence of iron deficiency, iron deficiency anaemia (IDA) and non-iron deficiency anaemia were 40.8%, 23.6% and 24.7%, respectively. The mean SF levels varied with maternal age, gestation stage, pregnancy intervals and the intake of iron supplements. The mean SF concentration was higher in the second trimester than in the third. The mean SF concentration ± standard deviation (37.10±3.02 µg/L) was higher in the group that took iron supplements than in the group that did not (20.76±2.11 µg/L). However, two out of five participants in both groups had SF concentrations less than 15.0 µg/L. CONCLUSION: The prevalence of IDA was quite high among the participants in both trimesters even with the widespread intake of the recommended oral iron supplements. About four out of 10 of the participants had SF concentrations of less than 15 µg/L and were thus judged at risk of giving birth to babies with poor iron deposits. Therefore, more effective strategies are needed to monitor and prevent IDA among pregnant women in rural populations of Nigeria and, by inference, other parts of tropical Africa.