Oral iron therapy: Current concepts and future prospects for improving efficacy and outcomes.

Iron deficiency (ID) and iron-deficiency anaemia (IDA) are global public health concerns, most commonly afflicting children, pregnant women and women of childbearing age. Pathological outcomes of ID include delayed cognitive development in children, adverse pregnancy outcomes and decreased work capacity in adults. IDA is usually treated by oral iron supplementation, typically using iron salts (e.g. FeSO4 ); however, dosing at several-fold above the RDA may be required due to less efficient absorption. Excess enteral iron causes adverse gastrointestinal side effects, thus reducing compliance, and negatively impacts the gut microbiome. Recent research has sought to identify new iron formulations with better absorption so that lower effective dosing can be utilized. This article outlines emerging research on oral iron supplementation and focuses on molecular mechanisms by which different supplemental forms of iron are transported across the intestinal epithelium and whether these transport pathways are subject to regulation by the iron-regulatory hormone hepcidin.

Effects of dietary sulfur amino acid levels on growth performance and intestinal immunity in broilers vaccinated and subsequently infected with coccidiosis.

Coccidia vaccination is a common practice in the poultry industry. However, research is lacking regarding the optimal nutritional support for coccidia vaccinated broilers. In this study, broilers were vaccinated with coccidia oocyst at hatch and were fed with a common starter diet from 1 to 10 d. On d 11, the broilers were randomly assigned to groups in a 4 × 2 factorial arrangement. Briefly, the broilers were fed one of four diets containing 0.6, 0.8, 0.9, and 1.0% of standardized ileal digestible methionine plus cysteine (SID M+C), respectively, from 11 to 21 d. On d 14, the broilers from each diet group were orally gavaged with either PBS (Mock challenge) or Eimeria oocysts. Compared to PBS-gavaged broilers and regardless of dietary SID M+C levels, the Eimeria-gavaged broilers had 1) decreased gain-to-feed ratio (15-21 d, P = 0.002; 11-21 d, P = 0.011); 2) increased fecal oocysts (P < 0.001); 3) increased plasma anti-Eimeria IgY (P = 0.033); and 4) increased intestinal luminal interleukin-10 (IL-10; duodenum, P = 0.039; jejunum, P = 0.018) and gamma interferon (IFN-γ; duodenum, P < 0.001; jejunum, P = 0.017). Regardless of Eimeria gavage, broilers fed 0.6% SID M+C had decreased (P<0.001) body weight gain (15-21 and 11-21 d) and gain-to-feed ratio (11-14, 15-21, and 11-21 d) when compared to those fed ≥ 0.8% SID M+C. Eimeria challenge increased (P < 0.001) duodenum lesions when the broilers were fed with 0.6, 0.8, and 1.0% SID M+C, and increased (P = 0.014) mid-intestine lesions when the broilers were fed with 0.6 and 1.0% SID M+C. An interaction between the two experimental factors was detected on plasma anti-Eimeria IgY titers (P = 0.022), as coccidiosis challenge increased plasma anti-Eimeria IgY titers only when the broilers were fed with 0.9% SID M+C. In summary, the dietary SID M+C requirement for grower (11-21 d) broilers vaccinated with coccidiosis was ranged from 0.8 to 1.0% for optimal growth performance and intestinal immunity, regardless of coccidiosis challenge.

Enzymatic Modification of Lecithin for Improved Antioxidant Activity in Combination with Tocopherol in Emulsions and Bulk Oil.

Oxidized α-tocopherol can be regenerated by phosphatidylethanolamine (PE), but current commercial sources of PE are too expensive for use as a food additive. The present study aims to determine the optimal reaction conditions for generating high PE lecithin (MHPEL) enzymatically and to validate the MHPEL's synergism with tocopherol in delaying lipid oxidation in an oil-in-water emulsion system at pH 7 and 4 and in bulk oil. Under optimal conditions of pH 9.0, 37 °C and 4 h, a MHPEL with ∼71.6% PE was obtained from 96% phosphatidylcholine lecithin using phospholipase D from Streptomyces chromofuscus. Mixed tocopherols (300 µmol/kg oil) and MHPEL (1500 µmol/kg oil) synergistically increased both the hydroperoxide and hexanal lag phase of lipid oxidation in stripped soybean oil-in-water emulsions at pH 7 by 3 days. At pH 4, this combination increased the hydroperoxide and hexanal lag phases by 3 and 2 days, respectively. The combination of 50 µmol/kg oil α-tocopherol and 1000 µmol/kg oil MHPEL also synergistically increased the hydroperoxide (5 days) and hexanal (4 days) lag phases in stripped bulk soybean oil. This approach represents a potential clean-label antioxidant system that could have commercial applications to decrease food waste.

Salve and Burdock: A Safe, Effective Amish Remedy for Treatment of Traumatic Wounds?

BACKGROUND: Amish patients show a demonstrated preference for traditional, herbal remedies over modern medical interventions such as skin grafting. One such remedy is a mixture of Burn & Wound Ointment (B & W Ointment; Holistic Acres, LLC; Newcomerstown, Ohio) and steeped burdock leaves. Although both have demonstrated some antimicrobial and wound healing properties, burdock and/or the combination of B & W Ointment and burdock has never been studied to determine its purported ability to reduce pain, prevent infection, and accelerate wound healing. METHODS: A retrospective chart review was performed on 6 Amish patients treated with salve and burdock leaves instead of skin grafting following complex traumatic wounds to determine whether the traditional treatment incurred any patient harm. RESULTS: The time of wound epithelialization and healing complications were noted, among other data points. Time to full epithelialization ranged from 1 to 7 months. Time to full wound healing was proportional to wound size. CONCLUSIONS: Although the treatment presented here is unconventional, it did not cause harm to the patients studied.

Violet 405-nm light: a novel therapeutic agent against common pathogenic bacteria.

BACKGROUND: The increasing incidence of healthcare-associated infections (HAIs) and multidrug-resistant organisms demonstrate the need for innovative technological solutions. Staphylococcus aureus, Streptococcus pneumonia, Escherichia coli, and Pseudomonas aeruginosa in particular are common pathogens responsible for a large percentage of indwelling medical device-associated clinical infections. The bactericidal effects of visible light sterilization (VLS) using 405-nm is one potential therapeutic under investigation. MATERIALS AND METHODS: Light-emitting diodes of 405-nm were used to treat varying concentrations of S aureus, S pneumonia, E coli, and P aeruginosa. Irradiance levels between 2.71 ± 0.20 to 9.27 ± 0.36 mW/cm2 and radiant exposure levels up to 132.98 ± 6.68 J/cm2 were assessed. RESULTS: Dose-dependent effects were observed in all species. Statistically significant reductions were seen in both Gram-positive and Gram-negative bacteria. At the highest radiant exposure levels, bacterial log10 reductions were E coli-6.27 ± 0.54, S aureus-6.10 ± 0.60, P aeruginosa-5.20 ± 0.84, and S pneumoniae-6.01 ± 0.59. Statistically significant results (<0.001*) were found at each time point. CONCLUSIONS: We have successfully demonstrated high-efficacy bacterial reduction using 405-nm light sterilization. The VLS showed statistical significance against both Gram-positive and Gram-negative species with the given treatment times. The ß-lactam antibiotic-resistant E coli was the most sensitive to VLS, suggesting light therapy could a suitable option for sterilization in drug-resistant bacterial species. This research illustrates the potential of using VLS in treating clinically relevant bacterial infections.

Vitamin D Deficiency Promotes Liver Tumor Growth in Transforming Growth Factor-ß/Smad3-Deficient Mice Through Wnt and Toll-like Receptor 7 Pathway Modulation.

Disruption of the TGF-ß pathway is associated with liver fibrosis and suppression of liver tumorigenesis, conditions associated with low Vitamin D (VD) levels. However, potential contributions of VD to liver tumor progression in the context of TGF-ß signaling remain unexplored. Our analyses of VD deprivation (VDD) in in vivo models of liver tumor formation revealed striking three-fold increases in tumor burden in Smad3(+/-) mice, with a three-fold increase in TLR7 expression compared to controls. ChIP and transcriptional assays confirm Smad3 binding at two TLR7 promoter SBE sites. Molecular interactions between TGF-ß pathway and VDD were validated clinically, where an absence of VD supplementation was associated with low TGF-ß pathway member expression levels and ß-catenin activation in fibrotic/cirrhotic human liver tissues. Subsequent supplementing VD led to restoration of TGF-ß member expression with lower ß-catenin levels. Bioinformatics analysis provides positive supportive correlation between somatic mutations for VD-related genes and the TGF-ß pathway. We conclude that VDD promotes tumor growth in the context of Smad3 disruption, potentially through regulation of TLR7 expression and ß-catenin activation. VD could therefore be a strong candidate for liver cancer prevention in the context of aberrant Smad3 signaling.

A Randomized Controlled Trial of Mindfulness-Based Cognitive Therapy for Treatment-Resistant Depression.

BACKGROUND: Due to the clinical challenges of treatment-resistant depression (TRD), we evaluated the efficacy of mindfulness-based cognitive therapy (MBCT) relative to a structurally equivalent active comparison condition as adjuncts to treatment-as-usual (TAU) pharmacotherapy in TRD. METHODS: This single-site, randomized controlled trial compared 8-week courses of MBCT and the Health Enhancement Program (HEP), comprising physical fitness, music therapy and nutritional education, as adjuncts to TAU pharmacotherapy for outpatient adults with TRD. The primary outcome was change in depression severity, measured by percent reduction in the total score on the 17-item Hamilton Depression Rating Scale (HAM-D17), with secondary depression indicators of treatment response and remission. RESULTS: We enrolled 173 adults; mean length of a current depressive episode was 6.8 years (SD = 8.9). At the end of 8 weeks of treatment, a multivariate analysis showed that relative to the HEP condition, the MBCT condition was associated with a significantly greater mean percent reduction in the HAM-D17 (36.6 vs. 25.3%; p = 0.01) and a significantly higher rate of treatment responders (30.3 vs. 15.3%; p = 0.03). Although numerically superior for MBCT than for HEP, the rates of remission did not significantly differ between treatments (22.4 vs. 13.9%; p = 0.15). In these models, state anxiety, perceived stress and the presence of personality disorder had adverse effects on outcomes. CONCLUSIONS: MBCT significantly decreased depression severity and improved treatment response rates at 8 weeks but not remission rates. MBCT appears to be a viable adjunct in the management of TRD.

Violet 405 nm light: A novel therapeutic agent against ß-lactam-resistant Escherichia coli.

BACKGROUND AND OBJECTIVE: Approximately 1.7 million patients are affected by hospital-acquired infections every year in the United States. The increasing prevalence of multidrug-resistant bacteria associated with these infections prompts the investigation of alternative sterilization and antibacterial therapies. One method currently under investigation is the antibacterial properties of visible light. This study examines the effect of a visible light therapy (VLT) on ß-lactam-resistant Escherichia coli, a common non-skin flora pathogen responsible for a large percentage of indwelling medical device-associated clinical infection. MATERIALS AND METHODS: 405 nm light-emitting diodes were used to treat varying concentrations of a common laboratory E. coli K-12 strain transformed with the pCIG mammalian expression vector. This conferred ampicillin resistance via expression of the ß-lactamase gene. Bacteria were grown on sterile polystyrene Petri dishes plated with Luria-Bertani broth. Images of bacterial growth colonies on plates were processed and analyzed using ImageJ. Irradiance levels between 2.89 ± 0.19 and 9.45 ± 0.63 mW cm(-2) and radiant exposure levels between 5.60 ± 0.39 and 136.91 ± 4.06 J cm(-2) were tested. RESULTS: VLT with variable irradiance and constant treatment time (120 minutes) demonstrated significant reduction (P < 0.001) in E. coli between an irradiance of 2.89 mW cm(-2) (81.70%) and 9.37 mW cm(-2) (100.00%). Similar results were found with variable treatment time with constant irradiance. Log10 reduction analysis produced between 1.98 ± 0.53 (60 minute treatment) and 6.27 ± 0.54 (250 minute treatment) log10 reduction in bacterial concentration (P < 0.001). CONCLUSIONS: We have successfully demonstrated a significant bacterial reduction using high intensity 405 nm light. Illustrating the efficacy of this technology against a ß-lactam-resistant E. coli is especially relevant to the need for novel methods of sterilization in healthcare settings. These results suggest that VLT using 405 nm light could be a suitable clinical option for eradication of ß-lactam-resistant E. coli. Visible light kills statistically significant concentrations of E. coli. Antibiotic-resistant Gram-negative bacteria exhibits sensitivity to 405 nm light. Greater than 6 log10 reduction in ß-lactam-resistant E. coli when treated with visible light therapy.

Psychosexual therapy and education in patients treated for cancer of the head and neck.

It is now widely accepted that cancer is a chronic disease, and in this context we have previously highlighted shortcomings in the assessment of problems with intimacy and sexuality in patients treated for cancer of the head and neck. In this paper we introduce established strategies for the diagnosis and treatment of psychosexual problems to support these patients, and describe our early experiences of their use. We include brief narratives and case reports to show how they have made a difference to patients and their partners.

Impact of diabetes on eye care service needs: the National Indigenous Eye Health Survey.

BACKGROUND: To assess the proportion of Australian Indigenous adults who require eye care services (separately among those with and without diabetes) and determine implications for eye care service planning. DESIGN: The National Indigenous Eye Health Survey (NIEHS) was a population-based study of 30 randomly selected geographical areas. PARTICIPANTS: The NIEHS included 1189 Indigenous adults aged 40-80 years. METHODS: A standardized eye examination was performed. MAIN OUTCOME MEASURE: The number requiring eye care services by diabetes status. RESULTS: Those with diabetes were older (median 53 years) than those without diabetes (median age 50 years), P < 0.001. The total estimated population-based need for annual eye care in the NIEHS population was 52% (n = 615), and of those 72% were people with diabetes. Among those with diabetes, 29% required further primary referral for diabetic retinopathy, 12% for cataract, 1% for trachomatous trichiasis and 5% for uncorrected distance refractive error. Among those without diabetes 13% required further primary referral for cataract, 0% for trachomatous trichiasis and 5% for uncorrected distance refractive error. CONCLUSION: This study has shown that among Indigenous adults, those with diabetes form 72% of those requiring an eye examination in any year. A key strategy to close the gap for vision for Australia's Indigenous population is to ensure those with diabetes undergo annual eye screening, have clearly defined care pathways and receive timely treatment. Establishing care pathways for those who have diabetes would also improve access to eye care services for others in the community.

Australian Football League clinics promoting health, hygiene and trachoma elimination: the Northern Territory experience.

Australia is the only developed country to suffer trachoma and it is only found in remote Indigenous communities. In 2009, trachoma prevalence was 14%, but through screening, treatment and health promotion, rates had fallen to 4% in 2012. More work needs to be done to sustain these declining rates. In 2012, 25% of screened communities still had endemic trachoma and 8% had hyperendemic trachoma. In addition, only 58% of communities had reached clean face targets in children aged 5-9 years. Australian Football League (AFL) players are highly influential role models and the community love of football provides a platform to engage and strengthen community participation in health promotion. The University of Melbourne has partnered with Melbourne Football Club since 2010 to run trachoma football hygiene clinics in the Northern Territory (NT) to raise awareness of the importance of clean faces in order to reduce the spread of trachoma. This activity supports Federal and state government trachoma screening and treatment programs. Between 2010 and 2013, 12 football clinics were held in major towns and remote communities in the NT. Almost 2000 children and adults attended football clinics run by 16 partner organisations. Awareness of the football clinics has grown and has become a media feature in the NT trachoma elimination campaign. The hygiene station featured within the football clinic could be adapted for other events hosted in remote NT community events to add value to the experience and reinforce good holistic health and hygiene messages, as well as encourage interagency collaboration.

A European patient record study on diagnosis and treatment of chemotherapy-induced anaemia.

PURPOSE: Patients with cancer frequently experience chemotherapy-induced anaemia (CIA) and iron deficiency. Erythropoiesis-stimulating agents (ESAs), iron supplementation and blood transfusions are available therapies. This study evaluated routine practice in CIA management. METHODS: Medical oncologists and/or haematologists from nine European countries (n=375) were surveyed on their last five cancer patients treated for CIA (n=1,730). Information was collected on tests performed at diagnosis of anaemia, levels of haemoglobin (Hb), serum ferritin and transferrin saturation (TSAT), as well as applied anaemia therapies. RESULTS: Diagnostic tests and therapies for CIA varied across Europe. Anaemia and iron status were mainly assessed by Hb (94%) and ferritin (48%) measurements. TSAT was only tested in 14%. At anaemia diagnosis, 74% of patients had Hb ≤ 10 g/dL, including 15% with severe anaemia (Hb <8 g/dL). Low-iron levels (ferritin ≤ 100 ng/mL) were detected in 42% of evaluated patients. ESA was used in 63%of patients, blood transfusions in 52 % and iron supplementation in 31% (74% oral, 26% intravenous iron). Only 30% of ESA-treated patients received a combination of ESA and iron supplementation. Blood transfusions formed part of a regular anaemia treatment regimen in 76% of transfused patients. Management practices were similar in 2009 and 2011. CONCLUSION: Management of anaemia and iron status in patients treated for CIA varies substantially across Europe. Iron status is only assessed in half of the patients. In contrast to clinical evidence, iron treatment is under utilised and mainly based on oral iron supplementation. Implementation of guidelines needs to be increased to minimize the use of blood transfusions.

Mindfulness-based cognitive therapy (MBCT) versus the health-enhancement program (HEP) for adults with treatment-resistant depression: a randomized control trial study protocol.

BACKGROUND: Major depressive disorder (MDD) is the leading cause of disability in the developed world, yet broadly effective treatments remain elusive. Up to 40% of patients with depression are unresponsive to at least two trials of antidepressant medication and thus have "treatment-resistant depression" (TRD). There is an urgent need for cost-effective, non-pharmacologic, evidence-based treatments for TRD. Mindfulness-Based Cognitive Therapy (MBCT) is an effective treatment for relapse prevention and residual depression in major depression, but has not been previously studied in patients with TRD in a large randomized trial. METHODS/DESIGN: The purpose of this study was to evaluate whether MBCT is an effective augmentation of antidepressants for adults with MDD who failed to respond to standard pharmacotherapy. MBCT was compared to an active control condition, the Health-Enhancement Program (HEP), which incorporates physical activity, functional movement, music therapy and nutritional advice. HEP was designed as a comparator condition for mindfulness-based interventions to control for non-specific effects. Originally investigated in a non-clinical sample to promote stress reduction, HEP was adapted for a depressed population for this study. Individuals age 18 and older with moderate to severe TRD, who failed to respond to at least two trials of antidepressants in the current episode, were recruited to participate. All participants were taking antidepressants (Treatment as usual; TAU) at the time of enrollment. After signing an informed consent, participants were randomly assigned to either MBCT or HEP condition. Participants were followed for 1 year and assessed at weeks 1-7, 8, 24, 36, and 52. Change in depression severity, rate of treatment response and remission after 8 weeks were the primary outcomes measured by the clinician-rated Hamilton Depression Severity Rating (HAM-D) 17-item scale. The participant-rated Quick Inventory of Depression Symptomology (QIDS-SR) 16-item scale was the secondary outcome measure of depression severity, response, and remission. DISCUSSION: Treatment-resistant depression entails significant morbidity and has few effective treatments. We studied the effect of augmenting antidepressant medication with MBCT, compared with a HEP control, for patients with TRD. Analyses will focus on clinician and patient assessment of depression, participants' clinical global impression change, employment and social functioning scores and quality of life and satisfaction ratings. TRIAL REGISTRATION: ClincalTrials.gov identifier: NCT01021254.

Synthesis of terminal uranium(IV) disulfido and diselenido compounds by activation of elemental sulfur and selenium.

Rare stakes: Terminal uranium(IV) disulfido and diselenido compounds, Tp*2U(E2) (E=S, Se), were synthesized by the activation of elemental chalcogens. Structural, spectroscopic, computational and magnetic studies of these species establish their tetravalency and highly polarized U-E bonds.

The association of religiosity with overweight/obese body mass index among Asian Indian immigrants in California.

OBJECTIVE: The aim of this study was to examine the association between religiosity and overweight or obese body mass index among a multi-religious group of Asian Indian immigrants residing in California. METHODS: We examined cross-sectional survey data obtained from in-language telephone interviews with 3228 mostly immigrant Asian Indians in the 2004 California Asian Indian Tobacco Survey using multivariate logistic regression. RESULTS: High self-identified religiosity was significantly associated with higher BMI after adjusting for socio-demographic and acculturation measures. Highly religious Asian Indians had 1.53 greater odds (95% CI: 1.18, 2.00) of being overweight or obese than low religiosity immigrants, though this varied by religious affiliation. Religiosity was associated with greater odds of being overweight/obese for Hindus (OR 1.54; 95% CI: 1.08, 2.22) and Sikhs (OR 1.88; 95% CI: 1.07, 3.30), but not for Muslims (OR 0.69; 95% CI: 0.28, 1.70). CONCLUSIONS: Religiosity in Hindus and Sikhs, but not immigrant Muslims, appears to be independently associated with greater body mass index among Asian Indians. If this finding is confirmed, future research should identify potentially mutable mechanisms by which religion-specific religiosity affects overweight/obesity risk.

Remodelling of vascular (surgical) services in the UK.

The last few years have seen major changes in the delivery of vascular services in the UK. An increasingly elderly population with greater expectations from their medical services has challenged established methods. It also became apparent that outcomes for low volume, high risk index vascular interventions such as abdominal aortic aneurysm repair were poor in the UK compared to the rest of Europe. Other ongoing challenges were the introduction of a national aortic aneurysm screening programme and the development of vascular surgery as a separate speciality. This article details the approach taken to modernise vascular services in the UK, using a quality framework agreed by vascular specialists, which drove the structural change to move vascular interventions into fewer, higher volume centres. The introduction of modern networks is designed to maintain services in surrounding hospitals without on site vascular inpatient services. The initial effects of this service remodelling are positive, with elective aortic aneurysm mortality rates falling nationally from 7.5 to 2.4 per cent.

The combined oral contraceptive pill containing drospirenone and ethinyl estradiol plus levomefolate calcium.

INTRODUCTION: Neural tube defects are the second most common congenital anomaly in the United States, although their incidence may be decreased by periconception folic acid supplementation. A new oral contraceptive containing drospirenone and ethinyl estradiol plus levomefolate calcium was formulated to decrease the risk of neural tube defects in pregnancies conceived while taking or shortly after discontinuing this pill. AREAS COVERED: Because of its novelty, very few studies have been performed to evaluate the efficacy, side effects and safety related to contraception, premenstrual dysphoric disorder and acne; therefore, literature evaluating similar contraceptives without levomefolate is reviewed. Additionally, we review studies evaluating the addition of levomefolate calcium to oral contraceptives containing 3 mg drospirenone and either 20 or 30 µg ethinyl estradiol. To date, no study has been performed to evaluate the effect this new oral contraceptive has on reducing the incidence of neural tube defects. EXPERT OPINION: This new pill has similar contraceptive efficacy, side effect, safety and benefits profile to other drospirenone-containing contraceptives. While also approved to prevent neural tube defects, no studies validate this claim and physician time is better spent counseling women, regardless of contraceptive choice, on the importance of folic acid supplementation during the child-bearing years.