The German sickle cell disease registry reveals a surprising risk of acute splenic sequestration and an increased transfusion requirement in patients with compound heterozygous sickle cell disease HbS/ß-thalassaemia and no or low HbA expression.

Patients with sickle cell disease (SCD) in Germany exhibit a substantial genetic diversity in the ß-globin genotype. Data collected by the national German SCD registry reflect this diversity and allowed us to analyze the phenotypes associated with different SCD genotypes. Our study focused on 90 patients with HbS/ß-thalassaemia (HbS/ß-thal) and compared these to patients with HbSS and HbSC. Patients with HbS/ß-thal were classified into three groups: HbS/ß0-thal (no HbA), HbS/ß+-thal (HbA < 14%), and HbS/ß++-thal (HbA≥14%). In comparison to HbSS, patients with HbS/ß++-thal had higher Hb-levels, lower hemolytic activity and rarely required red blood cell transfusions. HbS/ß0-thal and HbS/ß+-thal closely resembled each other and are jointly referred to as HbS/ß0/+-thal. Compared to HbSS, patients with HbS/ß0/+-thal experienced a similar frequency of vasoocclusive crises and degree of hemolysis. However, the frequency of red blood cell transfusions (0.6 vs. 0.39/year, p = .0049) and splenic sequestration crises (42.4 vs. 15.5% of patients, p = 3.799e-05) was higher in HbS/ß0/+-thal than in HbSS, but close to zero in HbS/ß++-thal. In conclusion, the level of HbA expression determines the phenotype of HbS/ß+-thal. HbS/ß-thal expressing no or little HbA is hematologically similar to HbSS, but causes a previously unknown high risk of splenic sequestration.

Restrictive versus liberal red blood cell transfusion strategies for people with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without haematopoietic stem cell support.

BACKGROUND: An estimated one-quarter to one-half of people diagnosed with haematological malignancies experience anaemia. There are different strategies for red blood cell (RBC) transfusions to treat anaemia. A restrictive transfusion strategy permits a lower haemoglobin (Hb) level whereas a liberal transfusion strategy aims to maintain a higher Hb. The most effective and safest strategy is unknown. OBJECTIVES: To determine the efficacy and safety of restrictive versus liberal RBC transfusion strategies for people diagnosed with haematological malignancies treated with intensive chemotherapy or radiotherapy, or both, with or without a haematopoietic stem cell transplant (HSCT). SEARCH METHODS: We searched for randomised controlled trials (RCTs) and non-randomised studies (NRS) in MEDLINE (from 1946), Embase (from 1974), CINAHL (from 1982), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2023, Issue 2), and eight other databases (including three trial registries) to 21 March 2023. We also searched grey literature and contacted experts in transfusion for additional trials. There were no language, date or publication status restrictions. SELECTION CRITERIA: We included RCTs and prospective NRS that evaluated restrictive versus liberal RBC transfusion strategies in children or adults with malignant haematological disorders receiving intensive chemotherapy or radiotherapy, or both, with or without HSCT. DATA COLLECTION AND ANALYSIS: Two authors independently screened references, full-text reports of potentially relevant studies, extracted data from the studies, and assessed the risk of bias. Any disagreement was discussed and resolved with a third review author. Dichotomous outcomes were presented as a risk ratio (RR) with a 95% confidence interval (CI). Narrative syntheses were used for heterogeneous outcome measures. Review Manager Web was used to meta-analyse the data. Main outcomes of interest included: all-cause mortality at 31 to 100 days, quality of life, number of participants with any bleeding, number of participants with clinically significant bleeding, serious infections, length of hospital admission (days) and hospital readmission at 0 to 3 months. The certainty of the evidence was assessed using GRADE. MAIN RESULTS: Nine studies met eligibility; eight RCTs and one NRS. Six hundred and forty-four participants were included from six completed RCTs (n = 560) and one completed NRS (n = 84), with two ongoing RCTs consisting of 294 participants (260 adult and 34 paediatric) pending inclusion. Only one completed RCT included children receiving HSCT (n = 6); the other five RCTs only included adults: 239 with acute leukaemia receiving chemotherapy and 315 receiving HSCT (166 allogeneic and 149 autologous). The transfusion threshold ranged from 70 g/L to 80 g/L for restrictive and from 80 g/L to 120 g/L for liberal strategies. Effects were reported in the summary of findings tables only for the trials that included adults to reduce indirectness due to the limited evidence contributed by the prematurely terminated paediatric trial. Evidence from RCTs Overall, there may be little to no difference in the number of participants who die within 31 to 100 days using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 451 participants; RR 1.00, 95% CI 0.27 to 3.70, P=0.99; very low-certainty evidence). There may be little to no difference in quality of life at 0 to 3 months using a restrictive compared to a liberal transfusion strategy, but the evidence is very uncertain (three studies; 431 participants; analysis unable to be completed due to heterogeneity; very low-certainty evidence). There may be little to no difference in the number of participants who suffer from any bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies; 448 participants; RR 0.91, 95% CI 0.78 to 1.06, P = 0.22; low-certainty evidence). There may be little to no difference in the number of participants who suffer from clinically significant bleeding at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (four studies; 511 participants; RR: 0.94, 95% CI 0.74 to 1.19, P = 0.60; low-certainty evidence). There may be little to no difference in the number of participants who experience serious infections at 0 to 3 months using a restrictive compared to a liberal transfusion strategy (three studies, 451 participants; RR: 1.20, 95% CI 0.93 to 1.55, P = 0.17; low-certainty evidence). A restrictive transfusion strategy likely results in little to no difference in the length of hospital admission at 0 to 3 months compared to a liberal strategy (two studies; 388 participants; analysis unable to be completed due to heterogeneity in reporting; moderate-certainty evidence). There may be little to no difference between hospital readmission using a restrictive transfusion strategy compared to a liberal transfusion strategy (one study, 299 participants; RR: 0.89, 95% CI 0.52 to 1.50; P = 0.65; low-certainty evidence). Evidence from NRS The evidence is very uncertain whether a restrictive RBC transfusion strategy: reduces the risk of death within 100 days (one study, 84 participants, restrictive 1 death; liberal 1 death; very low-certainty evidence); or decreases the risk of clinically significant bleeding (one study, 84 participants, restrictive 3; liberal 8; very low-certainty evidence). No NRS reported on the other eligible outcomes. AUTHORS' CONCLUSIONS: Findings from this review were based on seven studies and 644 participants. Definite conclusions are challenging given the relatively few included studies, low number of included participants, heterogeneity of intervention and outcome reporting, and overall certainty of evidence. To increase the certainty of the true effect of a restrictive RBC transfusion strategy on clinical outcomes, there is a need for rigorously designed and executed studies. The evidence is largely based on two populations: adults with acute leukaemia receiving intensive chemotherapy and adults with haematologic malignancy requiring HSCT. Despite the addition of 405 participants from three RCTs to the previous review's results, there is still insufficient evidence to answer this review's primary outcome. If we assume a mortality rate of 3% within 100 days, we would need a total of 1492 participants to have an 80% chance of detecting, at a 5% level of significance, an increase in all-cause mortality from 3% to 6%. Further RCTs are needed overall, particularly in children.

Reliability of hemoglobin A2 value as measured by the Premier Resolution system for screening of ß-thalassemia carriers.

OBJECTIVES: Accurate quantification of hemoglobin (Hb) A2 is vital for diagnosing ß-thalassemia carriers. This study aimed to assess the precision and diagnostic utility of HbA2 measurements using the new high-performance liquid chromatography (HPLC) method, Premier Resolution, in comparison to capillary electrophoresis (CE). METHODS: We analyzed 418 samples, previously identified as A2A by CE, using Premier Resolution-HPLC. We compared the results, established correlations, and determined an optimal HbA2 cutoff value for ß-thalassemia screening. Additionally, we prospectively evaluated the chosen cutoff value in 632 samples. Mutations in the ß- and α-globin genes were identified using polymerase chain reaction (PCR) techniques and DNA sequencing. RESULTS: HbA2 levels were consistently higher with Premier Resolution, yet there was a significant correlation with CE in all samples (bias, -0.33; r, 0.991), ß-thalassemia (bias, -0.27; r, 0.927), and non-ß-thalassemia carriers (bias, -0.36; r, 0.928). An HbA2 cutoff value of ≥4.0 % for ß-thalassemia screening achieved 100 % sensitivity and 99.6 % specificity. Further validation yielded sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 97.3 , 99.8, 97.3, 99.8, and 99.7 %, respectively. We also identified a rare ß-Hb variant, Hb La Desirade [HBB:c.389C>T], associated with ß-thalassemia and co-inherited with a single α-globin gene. CONCLUSIONS: The Premier Resolution HPLC is a reliable and accurate method for routine ß-thalassemia carrier screening, aligning with existing CE methods.

Molecular characterization of a novel homozygous deletion in ß-globin cluster causing (δß)0-Thalassemia among Tunisian family.

BACKGROUND: Deletions in the ß-globin cluster are uncommon and cause thalassemia (thal) with hereditary persistence of fetal hemoglobin. They constitute a heterogenous group of disorders characterized by absent or reduced synthesis of adult hemoglobin (Hb A) and increased synthesis of fetal hemoglobin (Hb F). Although the clinical severity of these disorders are asymptomatic owing to the increased Hb F levels, the molecular basis is very heterogenous due to the large deletions in the ß-globin cluster spanning both HBD and HBB genes. Here, we describe a Tunisian family carrying a novel deletion mutation causing (δß)°-thalassemia. METHODS: The amounts of hemoglobin fractions were measured by capillary electrophoresis of hemoglobin. Amplification and sequencing of different regions on the ß-gene cluster were performed by Sanger method. RESULTS: Family study and genetic analysis revealed a large deletion mutation in the ß-globin cluster of 14.5 kb (NG_000,007.3:g. 58,253 to g.72837del14584) at the homozygous state in the patient and at heterozygous state at the other members of the family. This deletion removes the HBD and HBB genes. CONCLUSIONS: In our knowledge, this new large deletion is described for the first time in the Tunisian population and in the world, designed Tunisian(δß)0 in Ithanet database (IthaID: 3971). Therefore, it is important to identify the deletion leading to δß-thalassemia carriers at the molecular level, to highlight the importance of recognizing the clinical features and implementing appropriate testing to clarify the diagnosis and manage the condition.

Spectrometry of cord blood and maternal blood for Hb-F and Hb-A and novel technology for non-invasive measurement of hemoglobin in mother and baby.

BACKGROUND: Human hemoglobin (Hb) is a tetrameric metalloporphyrin. Heme part contains iron radicle and porphyrin. The globin part has pairs of amino-acid chains. Healthy adults have "Hemoglobin-A" made of two alpha and two beta chains (α2 ß2) while a newborn baby has "Hemoglobin-A (α2 ß2)" and "Hemoglobin-F (α2 γ2)". There are few reports about absorption spectrometry of Hb in cord blood. We have here compared absorption spectrum of Hb in cord blood and maternal blood samples (adult blood samples) together. OBJECTIVE: This was done in two parts. Part 1 was about studying absorption spectrum of Hb in cord blood and maternal blood. Part 2 was about developing a comprehensive noninvasive technology and using the same for measurement of Hb in mother (adult) and new-born baby. DESIGN: Observational study. MATERIAL AND METHODS: Part 1. After IRB approval, 25 pregnant mothers enrolled for the study. Cord blood/neonatal blood samples were collected from placental end in ethylene diamine tetra-acetic acid (EDTA) tube after the delivery of fetus and placenta (venous blood). Maternal blood was collected by peripheral venepuncture before delivery/labor. Part 2. Using noninvasive technology for measurement of Hb in mother (adult) and new-born baby. After the necessary approval five pairs of mother and new-born were enrolled in the study to measure Hb by noninvasive method using our novel device. The novel device (SH-1) uses electromagnetic radiations of specific wavelengths between 520 and 580 nm. Light was projected on forehead for a few seconds, operating the light sources one by one. Of the projected light, some was reflected by the recipient's skin. This optical signal was collected by photosensors and converted to electrical signals. After amplification, this was then transmitted to processor unit. Later, Hbs values are displayed. The results were then tallied with standard laboratory methods in clinical laboratory. RESULTS: Part 1. As expected in our study; all blood samples showed Soret band of same peak and wavelength. We expected different spikes corresponding to four globin chains namely alpha, beta, gamma, and delta. But interestingly, both neonatal and maternal blood samples had identical peaks. Part 2. The results appear promising. The Hb as measured by noninvasive method matches well with standard laboratory test. SIGNIFICANCE: The energy level of Hb is low in deoxygenated state compared to oxyhemoglobin. In a state of high energy level, alpha and beta and gamma globin chains show obvious different peaks. Since cord blood and maternal sample was obviously venous or in deoxygenated state with low energy level, single peak of absorption was observed for all three globin chains. Since maternal and cord blood showed similar absorption spectra, it was possible to develop a common method for estimation of biomarkers - Hb in adults and new-borns alike.

A novel pre-clinical strategy to deliver antimicrobial doses of inhaled nitric oxide.

Effective treatment of respiratory infections continues to be a major challenge. In high doses (≥160 ppm), inhaled Nitric Oxide (iNO) has been shown to act as a broad-spectrum antimicrobial agent, including its efficacy in vitro for coronavirus family. However, the safety of prolonged in vivo implementation of high-dose iNO therapy has not been studied. Herein we aim to explore the feasibility and safety of delivering continuous high-dose iNO over an extended period of time using an in vivo animal model. Yorkshire pigs were randomized to one of the following two groups: group 1, standard ventilation; and group 2, standard ventilation + continuous iNO 160 ppm + methylene blue (MB) as intravenous bolus, whenever required, to maintain metHb <6%. Both groups were ventilated continuously for 6 hours, then the animals were weaned from sedation, mechanical ventilation and followed for 3 days. During treatment, and on the third post-operative day, physiologic assessments were performed to monitor lung function and other significative markers were assessed for potential pulmonary or systemic injury. No significant change in lung function, or inflammatory markers were observed during the study period. Both gas exchange function, lung tissue cytokine analysis and histology were similar between treated and control animals. During treatment, levels of metHb were maintained <6% by administration of MB, and NO2 remained <5 ppm. Additionally, considering extrapulmonary effects, no significant changes were observed in biochemistry markers. Our findings showed that high-dose iNO delivered continuously over 6 hours with adjuvant MB is clinically feasible and safe. These findings support the development of investigations of continuous high-dose iNO treatment of respiratory tract infections, including SARS-CoV-2.

Cognitive functioning and its associated factors among breast cancer patients on chemotherapy at Tikur Anbessa specialized hospital, Addis Ababa Ethiopia: an institution-based comparative cross-sectional study.

BACKGROUND: Breast cancer is the second leading cause of cancer in the world. It is the commonest type of cancer in Ethiopia. Cognitive problems are common among breast cancer patients. The study aimed to assess cognitive functioning and its associated factors among breast cancer patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia 2020. METHODS: Institution-based comparative cross-sectional study was conducted. Study subjects were 117 breast cancer patients on chemotherapy and 117 women without breast cancer who volunteered for the study. Data was collected from May-June 2020. The Mini-mental status exam (MMSE) was used to assess cognitive functioning. Data were entered into Epi Data version 4.6.0.2 and analyzed using STATA version 14 software. Univariable and multivariable linear regression model was fitted to identify factors associated with cognitive functioning. A two-tailed p-value less than 0.05 was used to declare statistical significance. RESULTS: Among the total breast cancer patients 41.9% were diagnosed with earlier sage of the diseases (stage I and II), while the rest 58.1% were diagnosed with stage III and stage IV breast cancer. A significant difference in the MMSE score was observed among breast cancer patients and controls (19.76 ± 5.29, 25.18 ± 4.68 p <  0.0001) respectively. In multivariable linear regression analysis being non-breast cancer (Adjusted beta coefficient (Adj.ß.coff). = 3.34, 95% CI (1.92-4.76) p <  0.001), hemoglobin gm/dl (Adj.ß.coff =0.34, 95% CI (0.04-0.63) p = 0.02), and primary education (Adj.ß.coff =2.98 95%CI (1.16-4.96) p = 0.001) secondary level and more education (Adj.ß.coff = 5.47, 95%CI (3.51-7.28) p < 0.001) were significantly associated with MMSE cognitive score. CONCLUSION: Breast cancer patients had lower mean MMSE scores when compared to non-breast cancer women. Higher hemoglobin level and higher level of education increase the MMSE cognitive score. Clinicians should incorporate routine screening of cognitive functioning for breast cancer patients and further study is required to evaluate cognitive impairment among breast cancer patients in Ethiopia.

Effect of oral rehydration solution versus spring water intake during exercise in the heat on muscle cramp susceptibility of young men.

BACKGROUND: Muscle cramp is a painful, involuntary muscle contraction, and that occurs during or following exercise is referred to as exercise-associated muscle cramp (EAMC). The causes of EAMC are likely to be multifactorial, but dehydration and electrolytes deficits are considered to be factors. This study tested the hypothesis that post-exercise muscle cramp susceptibility would be increased with spring water ingestion, but reduced with oral rehydration solution (ORS) ingestion during exercise. METHODS: Ten men performed downhill running (DHR) in the heat (35-36 °C) for 40-60 min to reduce 1.5-2% of their body mass in two conditions (spring water vs ORS) in a cross-over design. The body mass was measured at 20 min and every 10 min thereafter during DHR, and 30 min post-DHR. The participants ingested either spring water or ORS for the body mass loss in each period. The two conditions were counter-balanced among the participants and separated by a week. Calf muscle cramp susceptibility was assessed by a threshold frequency (TF) of an electrical train stimulation to induce cramp before, immediately after, 30 and 65 min post-DHR. Blood samples were taken before, immediately after and 65 min after DHR to measure serum sodium, potassium, magnesium and chroride concentrations, hematocrit (Hct), hemoglobin (Hb), and serum osmolarity. Changes in these varaibles over time were compared between conditions by two-way repeated measures of analysis of variance. RESULTS: The average (±SD) baseline TF (25.6 ± 0.7 Hz) was the same between conditions. TF decreased 3.8 ± 2.7 to 4.5 ± 1.7 Hz from the baseline value immediately to 65 min post-DHR for the spring water condition, but increased 6.5 ± 4.9 to 13.6 ± 6.0 Hz in the same time period for the ORS condition (P < 0.05). Hct and Hb did not change significantly (P > 0.05) for both conditions, but osmolarity decreased (P < 0.05) only for the spring water condition. Serum sodium and chloride concentrations decreased (< 2%) at immediately post-DHR for the spring water condition only (P < 0.05). CONCLUSIONS: These results suggest that ORS intake during exercise decreased muscle cramp susceptibility. It was concluded that ingesting ORS appeared to be effective for preventing EAMC.

Umbilical Cord Management at Term and Late Preterm Birth: A Meta-analysis.

CONTEXT: The International Liaison Committee on Resuscitation prioritized scientific review of umbilical cord management at term and late preterm birth. OBJECTIVE: To assess effects of umbilical cord management strategies (clamping timing and cord milking) in infants ≥34 weeks' gestational age. DATA SOURCES: Cochrane Central Register of Controlled Trials, Medline, PubMed, Embase, Cumulative Index to Nursing and Allied Health Literature, and trial registries searched July 2019. STUDY SELECTION: Two authors independently assessed eligibility of randomized controlled trials. DATA EXTRACTION: Two authors independently extracted data and assessed evidence certainty (Grading of Recommendations Assessment, Development and Evaluations). RESULTS: We identified 46 studies (9159 women and their infants) investigating 7 comparisons. Compared with early cord clamping (ECC) <30 seconds, delayed cord clamping (DCC) ≥30 seconds (33 studies), intact-cord milking (1 study), and cut-cord milking (2 studies) probably improve hematologic measures but may not affect survival without neurodisability, anemia in early infancy, or maternal postpartum hemorrhage. No differences in major neonatal morbidities are seen in studies comparing methods of optimizing placental transfusion (DCC versus cut-cord milking [3 studies], longer delays in clamping [7 studies], or physiologic parameters [3 studies]). Strategies that promote increased placental transfusion may be associated with greater phototherapy use. Evidence for all outcomes was low or very low certainty. LIMITATIONS: Incompleteness and low certainty of findings limit applicability. CONCLUSIONS: Compared with ECC, DCC or cord milking increases hemoglobin and hematocrit immediately after birth in infants ≥34 weeks' gestational age. The uncertain effects of DCC and cord milking compared with ECC on major morbidities limit usefulness of available evidence for policy and practice.

Wheat flour fortification with iron and other micronutrients for reducing anaemia and improving iron status in populations.

BACKGROUND: Anaemia is a condition where the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body's physiological needs. Fortification of wheat flour is deemed a useful strategy to reduce anaemia in populations. OBJECTIVES: To determine the benefits and harms of wheat flour fortification with iron alone or with other vitamins and minerals on anaemia, iron status and health-related outcomes in populations over two years of age. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, CINAHL, 21 other databases and two trials registers up to 21 July 2020, together with contacting key organisations to identify additional studies. SELECTION CRITERIA: We included cluster- or individually-randomised controlled trials (RCTs) carried out among the general population from any country, aged two years and above. The interventions were fortification of wheat flour with iron alone or in combination with other micronutrients. We included trials comparing any type of food item prepared from flour fortified with iron of any variety of wheat DATA COLLECTION AND ANALYSIS: Two review authors independently screened the search results and assessed the eligibility of studies for inclusion, extracted data from included studies and assessed risks of bias. We followed Cochrane methods in this review. MAIN RESULTS: Our search identified 3538 records, after removing duplicates. We included 10 trials, involving 3319 participants, carried out in Bangladesh, Brazil, India, Kuwait, Philippines, South Africa and Sri Lanka. We identified two ongoing studies and one study is awaiting classification. The duration of interventions varied from 3 to 24 months. One study was carried out among adult women and one trial among both children and nonpregnant women. Most of the included trials were assessed as low or unclear risk of bias for key elements of selection, performance or reporting bias. Three trials used 41 mg to 60 mg iron/kg flour, three trials used less than 40 mg iron/kg and three trials used more than 60 mg iron/kg flour. One trial used various iron levels based on type of iron used: 80 mg/kg for electrolytic and reduced iron and 40 mg/kg for ferrous fumarate. All included studies contributed data for the meta-analyses. Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added Iron-fortified wheat flour with or without other micronutrients added versus wheat flour (no added iron) with the same other micronutrients added may reduce by 27% the risk of anaemia in populations (risk ratio (RR) 0.73, 95% confidence interval (CI) 0.55 to 0.97; 5 studies, 2315 participants; low-certainty evidence). It is uncertain whether iron-fortified wheat flour with or without other micronutrients reduces iron deficiency (RR 0.46, 95% CI 0.20 to 1.04; 3 studies, 748 participants; very low-certainty evidence) or increases haemoglobin concentrations (in g/L) (mean difference MD 2.75, 95% CI 0.71 to 4.80; 8 studies, 2831 participants; very low-certainty evidence). No trials reported data on adverse effects in children (including constipation, nausea, vomiting, heartburn or diarrhoea), except for risk of infection or inflammation at the individual level. The intervention probably makes little or no difference to the risk of Infection or inflammation at individual level as measured by C-reactive protein (CRP) (mean difference (MD) 0.04, 95% CI -0.02 to 0.11; 2 studies, 558 participants; moderate-certainty evidence). Iron-fortified wheat flour with other micronutrients added versus unfortified wheat flour (nil micronutrients added) It is unclear whether wheat flour fortified with iron, in combination with other micronutrients decreases anaemia (RR 0.77, 95% CI 0.41 to 1.46; 2 studies, 317 participants; very low-certainty evidence). The intervention probably reduces the risk of iron deficiency (RR 0.73, 95% CI 0.54 to 0.99; 3 studies, 382 participants; moderate-certainty evidence) and it is unclear whether it increases average haemoglobin concentrations (MD 2.53, 95% CI -0.39 to 5.45; 4 studies, 532 participants; very low-certainty evidence). No trials reported data on adverse effects in children. Nine out of 10 trials reported sources of funding, with most having multiple sources. Funding source does not appear to have distorted the results in any of the assessed trials. AUTHORS' CONCLUSIONS: Fortification of wheat flour with iron (in comparison to unfortified flour, or where both groups received the same other micronutrients) may reduce anaemia in the general population above two years of age, but its effects on other outcomes are uncertain. Iron-fortified wheat flour in combination with other micronutrients, in comparison with unfortified flour, probably reduces iron deficiency, but its effects on other outcomes are uncertain. None of the included trials reported data on adverse side effects except for risk of infection or inflammation at the individual level. The effects of this intervention on other health outcomes are unclear. Future studies at low risk of bias should aim to measure all important outcomes, and to further investigate which variants of fortification, including the role of other micronutrients as well as types of iron fortification, are more effective, and for whom.

Weekly Vitamin D3 supplementation improves aerobic performance in combat sport athletes.

AbstractVitamin D3 supplementation can affect the strength and power of an athlete, however the effect on endurance performance remains unclear. Twenty-seven recreational male combat athletes with at least 12 months experience within combat sports were recruited (age: 24 ± 4 years, stature: 176 ± 6 cm, weight: 77 ± 14 kg). Participants completed baseline testing for blood haemoglobin and haematocrit, upper and lower body VO2peak and upper and lower body Wingate. Following testing participants were stratified to 50,000IU (D1), 80,000IU (D2) or 110,000IU (D3) of vitamin D3 per week. They then completed a 6-week placebo period followed by a 6-week supplementation period. Retesting was carried out after the placebo and supplementation period. There was a significant effect for time for haemoglobin and haematocrit, upper and lower body VO2peak and upper body Wingate power (P < 0.01) but no effect for dose of vitamin D given. Performance data were normalised to vitamin D intake and there was a moderate effect size between D1 and D2 for lower body VO2peak (d = 0.6), upper body VO2peak (d = 0.13) and upper body average power (d = 0.75), with a large effect size between D1 and D2 for haemoglobin (d = 1.19), haematocrit (d = 0.93) and upper body peak power (d = 0.95). There was a large effect size for D1 compared to D3 for all variables (d > 0.8). Therefore, there is no additional benefit to increasing dose above 50,000IU vitamin D per week. Given the endurance adaptations from vitamin D supplementation and the importance of endurance for combat performance, recreational combat athletes should supplement at 50,000IU per week for six weeks.

Changes in Optical Path Length Reveal Significant Potential Errors of Muscle Oxygenation Evaluation during Exercise in Humans.

PURPOSE: Near-infrared spectroscopy (NIRS), performed with a commonly available noninvasive tissue oxygenation monitoring device, is based on the modified Beer-Lambert law (MBLL). Although NIRS based on MBLL (NIRSMBLL) assumes that the optical path length (PL) is constant, the effects of changes in PL during exercise on muscle oxygenation calculated by MBLL are still incompletely understood. Thus, the purposes of this study were to examine the changes in optical properties during ramp incremental exercise and to compare muscle oxygen dynamics measured by time-resolved NIRS with those calculated based on MBLL. METHODS: Twenty-two healthy young men performed ramp incremental cycling exercise until exhaustion. Optical properties (reduced scattering coefficient and PL) and absolute oxygenated, deoxygenated, and total hemoglobin and myoglobin concentrations (oxy[Hb + Mb], deoxy[Hb + Mb], and total[Hb + Mb], respectively) at the vastus lateralis were continuously monitored by a three-wavelength (763, 801, and 836) time-resolved NIRS device. The values of oxy-, deoxy-, and total[Hb + Mb] were then recalculated by assuming constant PL. RESULTS: PL at all wavelengths statistically significantly shortened during exercise. In particular, PL at 763 nm was greatly shortened, and the average changes during exercise were a 9.8% ± 3.1% reduction. In addition, significant differences in the kinetics of oxy-, deoxy-, and total[Hb + Mb] between directly measuring PL and assuming constant PL were found. The average changes in measured PL and assuming constant PL-deoxy[Hb + Mb] were increases of 28.8 ± 16.0 µM and increases of 16.4 ± 9.3 µM, respectively. CONCLUSION: Assuming constant PL in NIRSMBLL significantly underestimated actual muscle oxy/deoxygenation as compared with measurements obtained by real-time PL determination. The percent degree of the underestimated oxy/deoxygenation was greater than the percent degree of the changes in PL.

Association of red blood cell size and physical fitness in a military male cohort: The CHIEF study.

Anemia manifested as reduced red blood cell (RBC) amounts or hemoglobin levels has been associated with lower cardiorespiratory fitness. However, the relationship of smaller RBC with physical fitness was unknown. We included 2933 non-anemic military males (hemoglobin levels: 11.1-15.9 g/dL and mean corpuscular volume (MCV) <100 fL) in Taiwan during 2014. Aerobic fitness was assessed by time for a 3000-meter run, and anaerobic fitness was evaluated by numbers of sit-ups and push-ups, each performed within 2 minutes. Multiple linear and logistic regression models adjusting for age, service specialty, lipid profiles, and hemoglobin levels were used to determine the associations. Microcytosis and normocytosis were defined as MCV ≤ 70 fL (n = 190) and MCV > 70 fL (n = 2743), respectively. The linear regression shows that as compared with microcytosis, normocytosis was associated with more numbers of sit-ups performed within 2 minutes (ß = 1.51, P-value = 0.02). The logistic regression also reveals that those males with microcytosis had higher probability as the worst 10% performers in the 2-minute push-up test (odds ratio: 1.91, 95% confidence intervals: 1.18-3.12). By contrast, there was no association of microcytosis with 3000-meter running time. Our study suggests that non-anemic microcytosis was associated with lower anaerobic fitness but not with aerobic fitness. Whether the causative factors for microcytosis such as iron deficiency status and thalassemia trait unavailable in the study might account for the relationship needs further investigations.

Constructing a Talent Identification Index System and Evaluation Model for Cross-Country Skiers.

A talent identification index system for male and female cross-country skiers in four age groups (11-12 years old, 13-14 years old, 15-16 years old, and 17-18 years old) was established. The system comprises five body shape indexes ( i =5): Leg-to-Body Ratio (LBR), body fat percentage, maturity status, spreaded brachia index, and upper extremity length. The physiological function indexes ( i =2) are VO2max and haemoglobin mass (Hb). The psychological indexes ( i =5) cover reaction time, perception speed, a quality-of-will scale, an attention test, and operational thinking. The physical fitness indexes ( i =11) comprise upper limb explosiveness, vertical jump, 3000-metre run, orthostatic forward flexion, closed-eyes single-leg stand, standing long jump, 20-metre sprint, pull-ups (males), flexed arm hang (females), hexagon jump, and a Functional Movement Screen (FMS) test. The athletic performance indexes ( i =3) comprise on-snow time trials for 1.2 km, 5 km, and 10 km. The talent identification evaluation model was created using automated evaluation software. The talent identification index system and evaluation standard table for cross-country skiers passed the P60 shortlist and P90 elite boundaries established using the percentile method. Thus, the results of this test profile verify that the evaluative model is objectively effective.

Associations between legal performance-enhancing substance use and future cardiovascular disease risk factors in young adults: A prospective cohort study.

BACKGROUND: Legal performance-enhancing substances (PES), such as creatine, are commonly used by adolescents and young adults. As PES are mostly unregulated by the US Food and Drug Administration, there has been limited empirical attention devoted to examining their long-term safety and health outcomes. Preliminary studies have demonstrated associations between PES use and severe medical events, including hospitalizations and death. PES could be linked to cardiovascular disease (CVD), the most common cause of mortality in the US, by altering the myocardium, vasculature, or metabolism. The objective of this study was to examine prospective associations between the use of legal PES in young adulthood and CVD risk factors at seven-year follow-up. MATERIALS AND METHODS: Nationally representative longitudinal cohort data from the National Longitudinal Study of Adolescent to Adult Health, Waves III (2001-2002) and IV (2008), were analyzed. Regression models determined the prospective association between the use of legal PES (e.g. creatine monohydrate) and CVD risk factors (e.g. body mass index, diabetes, hypertension, hyperlipidemia), adjusting for relevant covariates. RESULTS: Among the diverse sample of 11,996 male and female participants, no significant differences by PES use in body mass index, diabetes, hypertension, or hyperlipidemia were noted at Wave III. In unadjusted comparisons, legal PES users (versus non-users) were more likely to be White, be male, be college educated, drink alcohol, and engage in weightlifting, exercise, individual sports, team sports, and other strength training. There were no significant prospective associations between legal PES use at Wave III and body mass index, hemoglobin A1c, systolic and diastolic blood pressure, and cholesterol (total, HDL, LDL, triglycerides) deciles at seven-year follow-up (Wave IV), adjusting for demographics, health behaviors, and Wave III CVD risk factors. Similarly, there were no significant prospective associations between legal PES use and diabetes, hypertension, or hyperlipidemia based on objective measures or self-reported medications and diagnoses, adjusting for demographics, health behaviors, and Wave III CVD risk. CONCLUSIONS: We do not find evidence for a prospective association between legal PES use and CVD risk factors in young adults over seven years of follow-up, including BMI, diabetes, hypertension, or hyperlipidemia. It should be noted that legal PES use was operationalized dichotomously and as one broad category, which did not account for frequency, amount, or duration of use. Given the lack of regulation and clinical trials data, observational studies can provide much needed data to inform the safety and long-term health associations of legal PES use and, in turn, inform clinical guidance and policy.

Prevalence of iron deficiency among university kendo practitioners in Japan: an observational cohort study.

BACKGROUND: Iron deficiency is widely recognized as being the cause of anemia in athletes, although iron status in athletes of Kendo, a traditional Japanese martial art based on swordsmanship and practiced as an educational sport, has not been widely investigated. METHODS: We performed a health assessment on anemia and serum ferritin levels, along with nutrient intake evaluation, for Kendo practitioners in a university in Japan. RESULTS: A total of 56 Kendo practitioners (39 male and 17 female) aged between 18 and 23 years participated in the study. No individuals exhibited WHO-defined anemia (less than 13 or 12 g/dL of hemoglobin levels in male or female), while hypoferritinemia (less than 30 ng/mL) was found in seven (41%) females but not in males. Significantly higher body mass index was found in the female athletes with hypoferritinemia compared to females with normo-ferritinemia in sub-analysis (median [interquartile range]; 25.6 [24.2, 26.9] versus 22.6 [21.7, 24.1], respectively. p < 0.05). No significant differences in the intake of iron were registered between males and females (with and without hypoferritinemia) using data from a food-frequency questionnaire survey. CONCLUSION: No apparent anemia was found in adolescent Kendo practitioners, although this study confirmed the presence of hypoferritinemia in several female athletes. Careful follow-up, involving both clinical and nutritional assessment, will be necessary for them to prevent progression into anemia. A future study with larger cohorts in multiple sites is warranted to assess the prevalence of iron deficiency for validation and, if necessary, to devise a strategy for improving the iron status in Kendo athletes.

Association between haematological parameters and sickle cell genotypes in children with Plasmodium falciparum malaria resident in Kisumu County in Western Kenya.

BACKGROUND: Sickle cell disease (SCD) is a monogenic disorder due to point mutation in the ß-globin gene resulting in substitution of Valine for Glutamic acid. The SCD is prevalent in P. falciparum endemic regions such as western Kenya. Carriage of different sickle cell genotypes may influence haematological parameter during malaria. Children resident in malaria holoendemic regions suffer more from malaria-related complications and this is moderated by the presence of the SCD. In the current study, we determined the association between sickle cell genotypes and haematological parameters in children with P. falciparum malaria resident in Kisumu County in Western Kenya. METHODOLOGY: Children (n = 217, aged 1-192 months) with acute febrile condition were recruited at Jaramogi Oginga Odinga Teaching and Referral Hospital. Chi-square (χ2) analysis was used to determine differences between proportions. Differences in haematological parameters were compared across groups using Kruskal Wallis test and between groups using Mann Whitney U test. Multivariate logistic regression analysis controlling for infection status was used to determine the association between sickle cell genotypes and haematological parameters. RESULTS: Using HbAA as the reference group, multivariate logistic regression analysis revealed that carriage of HbSS was associated with reduced haemoglobin [OR = 0.310, 95% CI = 0.101-0.956, P = 0.041], reduced haematocrit [OR = 0.318, 95% CI = 0.128-0.793, P = 0.014], reduced RBC count [OR = 0.124, 95% CI = 0.045-0.337, P = 0.001], reduced MCHC [OR = 0.325, 95% CI = 0.118-0.892, P = 0.029], increased leucocytosis [OR = 9.283, 95% CI = 3.167-27.210, P = 0.001] and reduced monocytosis [OR = 0.319, 95% CI = 0.123-0.830, P = 0.019]. However, carriage of HbAS was only associated with increased micro-platelets [OR = 3.629, 95% CI = 1.291-8.276, P = 0.012]. CONCLUSION: Results show that carriage of HbSS in children influence the levels of haemoglobin, haematocrit, RBC, MCHC, WBC and Monocytes. Therefore prior knowledge of HbSS should be considered to improve clinical management of haematological alterations during malaria in children.