Perinatal intervention strategies providing food with micronutrients to pregnant and breastfeeding women in low- and middle-income countries: A scoping review.

In resource-constrained settings, pregnant and breastfeeding women and girls (PBW/G) are particularly vulnerable to undernutrition. Micronutrient-fortified balanced energy protein (BEP) supplementation may be provided to boost maternal nutritional status and improve birth and infant outcomes. We conducted a scoping review of the published literature to determine the impact of BEP and other related nutrition interventions that provided fortified food or cash along with a minimum of 3 micronutrients on maternal, birth, and infant/child outcomes in low- and middle-income countries. We conducted a PubMed search using pre-defined keywords and controlled vocabulary search terms. All titles and abstracts were reviewed for eligibility by two independent reviewers, and data were extracted according to outcome type. We identified 149 eligible research articles that reported on a total of 21 trials and/or programme evaluations which assessed the health impact of one or more products (fortified lipid-based nutrient supplement [LNS, n = 12], fortified blended flours [n = 5], milk-based beverages [n = 2], and local food/snacks [n = 3]) that provided 118-750 kcal/day and varying levels of protein and micronutrients. Only one of these programme evaluations assessed the impact of the provision of cash and fortified food. Effects on maternal outcomes such as gestational weight gain and duration of gestation were promising but inconsistent. Birth outcomes were reported in 15 studies, and the effects on birthweight and birth length were generally positive. Seven studies demonstrated sustained benefits on infant and child growth out of the 15 studies that reported at least one of these outcomes, although data were sparse. Additional research is needed to investigate issues of dose, cost-effectiveness, and incorporation into multi-component interventions.

Contribution of socio-economic and demographic factors to maternal and child malnutrition in Bangladesh: Insights from a nationwide survey.

Background: Malnutrition is a major global public health issue, especially for under five children and their mothers. Objective: This study examined the relationships between socio-economic and demographic characteristics and under- and over-nutrition in mothers and children of Bangladesh. Method: Using the Nationally representative Bangladesh Demographic and Health Survey (2017-18) data, we performed the multiple logistic regression analysis to assess the relationships between key outcome variables and predictors. The analysis included 8321 children aged 0-59 months and 7800 mothers aged 15-49 years. Findings: The prevalence of stunting, wasting, and overweight among children under five was 30.72%, 8.44%, and 2.21% respectively. About 2.74% of the children were both stunted and wasted, while 0.56% of the children were both stunted and overweight. The prevalence of underweight and overweight among mother was 14.09% and 26.35% respectively. Children who are stunted are significantly associated with the mother's BMI status, mothers' education, fathers' education, and wealth index, while children who are wasted are significantly associated with the mother's BMI status and the child's sex. A child's sex and birth order are significantly associated with children being overweight. Mother's age, mother's education, father's education, place of residence and wealth index are significant determinants for mothers being underweight, whereas mother's age, mother's occupation, father's education, father's occupation, place of residence and wealth index are significant determinants for mothers being overweight. Conclusion: In addition to essential nutrition interventions, it is vital to address the basic social-economic and demographic determinants.

The value of the urinary protein:creatinine ratio for the detection of significant proteinuria in women with suspected preeclampsia.

To explore the correlation between urinary protein:creatinine ratio and 24-h excretion of protein, we studied 149 women referred to a day assessment unit for investigations for suspected preeclampsia. Paired samples were obtained for measurement of urinary protein:creatinine ratio and 24-h protein excretion. Collection of a 24-h urine sample was validated by the daily creatinine excretion. The outcome measure was proteinuria of 300 mg/day or more. Inaccurate 24-h collection was observed in 17% of women. All women (n = 56) with a protein:creatinine ratio >60 mg/mM had significant proteinuria. No woman with protein:creatinine ratio <18 mg/mM (n = 20) had significant proteinuria. We recommend that a dual cut-off should be used for excluding and "ruling in" the diagnosis of significant proteinuria. A 24-h urine collection should be used only for urinary protein:creatinine ratio values between 18 and 60 mg/mM in the detection of significant proteinuria.

Options to avoid the second surgical site: a review of literature.

As esthetics gain importance, periodontal plastic surgical procedures involving soft tissue grafts are becoming commoner both around natural teeth as well as around implants. Periodontal soft tissue grafts are primarily used for the purpose of root coverage and in pre-prosthetic surgery to thicken a gingival site or to improve the crestal volume. Soft tissue grafts are usually harvested from the palate. Periodontal plastic surgical procedures involving soft tissue grafts harvested from the palate have two surgical sites; a recipient site and another donor site. Many patients are apprehensive about the soft tissue graft procedures, especially the creation of the second/donor surgical site in the palate. In the past decade, newer techniques and products have emerged which provide an option for the periodontist/patient to avoid the second surgical site. MucoMatrixX, Alloderm(®), Platelet rich fibrin, Puros(®) Dermis and Mucograft(®) are the various options available to the practicing periodontist to avoid the second surgical site. Use of these soft tissue allografts in an apprehensive patient would decrease patient morbidity and increase patient's acceptance towards periodontal plastic surgical procedures.

Effectiveness of Postnatal Maternal or Caregiver Interventions on Outcomes among Infants under Six Months with Growth Faltering: A Systematic Review.

The care of infants at risk of poor growth and development is a global priority. To inform new WHO guidelines update on prevention and management of growth faltering among infants under six months, we examined the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants between 0 and 6 months. We searched nine electronic databases from January 2000 to August 2021, included interventional studies, evaluated the quality of evidence for seven outcome domains (anthropometric recovery, child development, anthropometric outcomes, mortality, readmission, relapse, and non-response) and followed the GRADE approach for certainty of evidence. We identified thirteen studies with preterm and/or low birth weight infants assessing effects of breastfeeding counselling or education (n = 8), maternal nutrition supplementation (n = 2), mental health (n = 1), relaxation therapy (n = 1), and cash transfer (n = 1) interventions. The evidence from these studies had serious indirectness and high risk of bias. Evidence suggests breastfeeding counselling or education compared to standard care may increase infant weight at one month, weight at two months and length at one month; however, the evidence is very uncertain (very low quality). Maternal nutrition supplementation compared to standard care may not increase infant weight at 36 weeks postmenstrual age and may not reduce infant mortality by 36 weeks post-menstrual age (low quality). Evidence on the effectiveness of postnatal maternal or caregiver interventions on outcomes among infants under six months with growth faltering is limited and of 'low' to 'very low' quality. This emphasizes the urgent need for future research. The protocol was registered with PROSPERO (CRD42022309001).

Factors influencing delivery-related complications and their consequences in hard-to-reach areas of Bangladesh.

BACKGROUND AND OBJECTIVES: Bangladesh's high maternal mortality ratio is exacerbated by delivery-related complications, particularly in hard-to-reach (HtR) areas with limited healthcare access. Despite this, few studies have explored delivery-related complications and factors contributing to these complications among the disadvantaged population. This study aimed to investigate the factors contributing to delivery-related complications and their consequences among the mothers residing in the HtR areas of Bangladesh. METHODS: Data were collected using a cross-sectional study design from 13 HtR sub-districts of Bangladesh between September 2019 and October 2019. Data from 1,290 recently delivered mothers were analysed. RESULTS: Around 32% (95% CI: 29.7-34.8) of the mothers reported at least one delivery-related complication. Prolonged labour pain (21%) was the highest reported complication during the delivery, followed by obstructive labour (20%), fever (14%), severe headache (14%). Mothers with higher education, a higher number of antenatal care (ANC) visits, complications during ANC, employed, and first-time mothers had higher odds of reporting delivery-related complications. More than one-half (51%) of these mothers had normal vaginal delivery. Nearly one-fifth (20%) of mothers who reported delivery-related complications were delivered by unskilled health workers at homes. On the other hand, about one-fifth (19%) of the mothers without any complications during delivery had a caesarean delivery. Nine out of ten of these caesarean deliveries were done at the private facilities. CONCLUSION: Delivery-related complications are significantly related to a woman's reproductive history and other background characteristics. Unnecessary caesarean delivery is prominent at private facilities.

RBCK1, an E3 ubiquitin ligase, interacts with and ubiquinates the human pregnane X receptor.

The pregnane X receptor (PXR, NR1I2) plays a pivotal role in the disposition and detoxification of numerous foreign and endogenous chemicals by increasing transcription of numerous target genes, including phase I and II drug-metabolizing enzymes and transporters. In the present study, yeast two-hybrid screening identified an E3 ubiquitin ligase, RBCK1 (Ring-B-box-coiled-coil protein interacting with protein kinase C-1), as a human pregnane X receptor (hPXR)-interacting protein. Coimmunoprecipitation studies confirmed the interaction between RBCK1 and hPXR when both were ectopically expressed in AD-293 cells. Domain mapping studies showed that the interaction between RBCK1 and hPXR involves all RBCK1 domains. We further demonstrate that RBCK1 ubiquitinates hPXR, and this may target hPXR for degradation by the ubiquitin-proteasome pathway. Simultaneous ectopic overexpression of RBCK1 and PXR decreased PXR levels in AD-293 cells, and this decrease was inhibited by the proteasomal inhibitor MG-132 (carbobenzoxy-Leu-Leu-leucinal). Furthermore, overexpression of RBCK1 decreased endogenous levels of PXR in HepG2 cells. Of importance, ectopic overexpression and silencing of endogenous RBCK1 in primary human hepatocytes resulted in a decrease and increase, respectively, in endogenous PXR protein levels and in the induction of PXR target genes by rifampicin. These results suggest that RBCK1 is important for the ubiquitination of PXR and may play a role in its proteasomal degradation.

Effect of different cooking methods on iodine losses.

Iodine Deficiency Disorders (IDD) is a public health problem in India. It is because of poor iodine availability to the body either due to loss of iodine from iodized salt or due to cooking. Since there is lack of scientific evidence on loss of iodine during different cooking methods, present study was undertaken to study the effect of different cooking methods on iodine losses. Methods used were boiling, roasting, shallow frying, deep frying, pressure cooking and microwave cooking. The loss of iodine ranged from 6.58% to 51.08%. Minimum losses were found during shallow frying where cooking time of salt was 1 min and 15 s and maximum during pressure cooking where cooking time of salt was 26 min. Losses during boiling, roasting, deep frying and microwave cooking were found to be 40.23%, 10.57%, 10.40% and 27.13% respectively. From the obtained results, authors have concluded that the loss of iodine depends upon type of cooking method and time of addition of salt during cooking.

Effectiveness of Interventions to Manage Difficulties with Breastfeeding for Mothers of Infants under Six Months with Growth Faltering: A Systematic Review Update.

(1) Background: The current evidence on management of infants under six months (u6m) with growth faltering is limited and of low quality. This review aimed at updating an existing review to inform the WHO guideline update on prevention and management of growth faltering in infants u6m. The objective is to synthesise evidence on interventions to manage breastfeeding difficulties in mothers or caregivers of infants u6m with growth faltering to improve breastfeeding practices and breastmilk intake. (2) Methods: We searched PubMed, CINAHL, and Cochrane Library from December 2018 to December 2021 for experimental studies. Using RoB 2.0 and ROBINS-I tools, we assessed study quality and results were synthesised narratively. Using the GRADE approach, we assessed the quality of evidence for four outcome domains-breastfeeding (critical), anthropometric (important), mortality (important), and morbidity (important). (3) Results: We identified seven studies, conducted among neonates (mainly preterm, n = 14 to 607), and assessed the following interventions: (a) non-nutritive sucking (NNS) on breast (n = 2) and (b) alternative supplemental feeding techniques (n = 5, cup feeding, spoon feeding, supplemental feeding tube device, and syringe feeding), and reported breastfeeding and anthropometric outcomes. None of the studies reported mortality and morbidity outcomes. The reported breastfeeding outcomes included LATCH (Latch, Audible swallowing, Type of nipple, Comfort, Hold) total score, PIBBS (Preterm Infants Breastfeeding Behaviour Scale) total score, EBF (exclusive breastfeeding) at various time points and time to transition to full breastfeeding, and reported anthropometric outcomes included weight gain and weight at different time points. Studies had 'serious' indirectness and 'serious' to 'very serious' risks of bias. From the limited studies we found, NNS on breast compared to NNS on finger may have some benefits on PIBBS total score; NNS on breast compared to NNS on pacifier may have some benefits on EBF at discharge; and cup feeding compared to bottle feeding may have some benefits on EBF at discharge, at three months and at six months. (4) Conclusions: Evidence on the effectiveness of interventions to manage breastfeeding difficulties in mothers or caregivers of infants u6m with growth faltering to improve breastfeeding practices and increase breastmilk intake is 'limited' and of 'low' to 'very low' quality. As the majority of the infants in the included studies were neonates, no new recommendations can be made for infants from one to six months due to lack of evidence in this population. We need more studies targeting infants from one to six months of age. The review was registered with PROSPERO (CRD42022309001).

Mapping the range of policies relevant to care of small and nutritionally at-risk infants under 6 months and their mothers in Ethiopia: a scoping review protocol.

INTRODUCTION: Evidence gaps limit management of small and/or nutritionally at-risk infants under 6 months and their mothers, who are at higher risk of death, illness, malnutrition and poor growth and development. These infants may be low birth weight, wasted, stunted and/or underweight. An integrated care model to guide their management (MAMI Care Pathway) is being tested in a randomised controlled trial in Ethiopia. Evaluating the extent to which an innovation is consistent with national policies and priorities will aid evidence uptake and plan for scale. METHODS AND ANALYSIS: This review will evaluate the extent to which the MAMI Care Pathway is consistent with national policies that relate to the care of at-risk infants under 6 months and their mothers in Ethiopia. The objectives are to describe the range and characteristics, concepts, strategic interventions, coherence and alignment of existing policies and identify opportunities and gaps. It will be conducted in accordance with the JBI methodology for scoping reviews (PRISMA-ScR). Eligible documents include infant and maternal health, nutrition, child development, food and social welfare-related policies publicly available in English and Amharic. The protocol was registered on the Open Science Framework Registry on 20 June 2022 (https://osf.io/m4jt6).Grey literature will be identified through government and agency websites, national and subnational contacts and Google Scholar, and published policies through electronic database searches (MEDLINE, EMBASE and Global and Health Information). The searches will take place between October 2023 and March 2024. A standardised data extraction tool will be used. Descriptive analysis of data will be undertaken. Data will be mapped visually and tabulated. Results will be described in narrative form. National stakeholder discussions will inform conclusions and recommendations. ETHICS AND DISSEMINATION: Ethical approval is not required as data consist solely of publicly available material. Findings will be used to evidence national and international policy and practice.

Impact of Nutrition Interventions for Reduction of Anemia in Women of Reproductive Age in Low- and Middle-Income Countries: A Meta-Review.

Background: The UN Sustainable Development Goal aims at a 50% reduction of anemia in women of reproductive age (WRA) by 2030. Several nutrition-specific and sensitive interventions are targeted across low- and middle-income countries (LMICs) to reduce anemia. Objectives: In this meta-review we comprehensively assessed the effectiveness of nutrition-specific and -sensitive interventions on hemoglobin (Hb) and serum ferritin (SF) concentrations and the prevalence of iron deficiency and anemia among WRA, pregnant women, and lactating women from LMICs. Method: The preparation of the present meta-review followed a double-blinded synthesis process with 3 stages: screening, quality appraisal, and data extraction in Eppi Reviewer. A comprehensive search was performed for systematic reviews (SRs) published between January 2000 and May 2022 using 21 international, national, and regional databases. The methodological quality appraisal of included studies was conducted using the Assessing the Methodological Quality of Systematic Reviews (AMSTAR) checklist. Results: A total of 23 SRs evaluated the effects of various nutrition-specific interventions included in the final synthesis. The included SRs included analyses of nutrition-specific interventions such as supplementation of the nutrients iron (n = 7), iron and folic acid (n = 4), vitamin A (n = 3), calcium (n = 2), multiple micronutrients (n = 7), and intravenous iron sucrose (n = 2). Also, SRs on fortification of nutrients included multiple micronutrients (n = 6), iron and folic acid (n = 4), and iron (n = 4). Of the 23 SRs, 22 were of high quality. Iron with or without folic acid supplementation and fortification and vitamin A supplementation consistently showed positive effects on either reduction in the prevalence of anemia or iron deficiency and improving the Hb or SF concentrations in WRA and pregnant women from LMICs. Conclusion: The comprehensive meta-review reported the beneficial effects of iron with or without folic acid, multiple micronutrient supplementation/fortification, and vitamin A supplementation in reducing the prevalence of anemia or iron deficiency and increasing Hb or SF concentrations in WRA from LMICs.

Carers' and health workers' perspectives on malnutrition in infants aged under six months in rural Ethiopia: A qualitative study.

OBJECTIVES: Supporting small and nutritionally at-risk (potentially malnourished) infants under six months is a global health priority, albeit with a weak evidence-base. To inform policy and research in this area, we aimed to assess the perceptions and understanding of infant malnutrition and its management among carers, communities, and healthcare workers in rural Ethiopia. METHODS: We conducted in-depth and key-informant interviews, from May-August 2020 in Jimma Zone and Deder District, Ethiopia. We used purposive sampling to recruit the participants. Interviews were transcribed into Amharic or Afaan Oromo and then translated into English. Atlas ti-7 was used to support data analysis. Findings were narrated based on the different themes arising from the interviews. RESULTS: Carers/community members and healthcare workers reported on five different themes: 1) Perceptions about health and well-being: an 'ideal infant' slept well, fed well, was active and looked 'fat'; 2)Perceptions of feeding: overall knowledge of key recommendations like exclusive breastfeeding was good but practices were suboptimal, notably a cultural practice to give water to young infants; 3)Awareness about malnutrition: a key limitation was knowledge of exactly how to identify small and nutritionally at-risk infants; 4) Reasons for malnutrition: levels of understanding varied and included feeding problems and caregiver's work pressures resulting in the premature introduction of complementary feeds; 5) Perceptions about identification & treatment: carers prefer treatment close to home but were concerned about the quality of community-based services. CONCLUSION: To succeed, research projects that investigate programes that manage small and nutritionally at-risk infants under six months should understand and be responsive to the culture and context in which they operate. They should build on community strengths and tackle misunderstandings and barriers. Interventions beyond just focusing on knowledge and attitude of the carers and health workers are necessary to tackle the challenges around infants under 6 months of age at risk of malnutrition. Moreover, stakeholders beyond the health sector should also be involved in order to support the infants under 6 months and their mothers as some of the key reasons behind the at-risk infants are just beyond the capacity of the health sector or health system. Our list of themes could be used to inform infant nutrition work not just in Ethiopia but also in many others.

NCOA6 differentially regulates the expression of the CYP2C9 and CYP3A4 genes.

CYP2Cs and CYP3A4 sub families of enzymes of the Cytochrome P450 super family metabolize clinically prescribed therapeutics. Constitutive and induced expressions of these enzymes are under the control of HNF4α and rifampicin activated PXR. In the present study, we show a mechanism for ligand dependent synergistic cross talk between PXR and HNF4α. Two-hybrid screening identified NCOA6 as a HNF4α interacting protein. NCOA6 was also found to interact with PXR through the first LXXLL motif in GST pull down and mammalian two hybrid assays. NCOA6 enhances the synergistic activation of CYP2C9 and CYP3A4 promoter activity by PXR and HNF4α in the presence of rifampicin. However silencing NCOA6 abrogated the synergistic activation and induction of CYP2C9 by PXR-HNF4α but not of CYP3A4. ChIP analysis revealed that NCOA6 could bridge HNF4α and PXR binding sites of the CYP2C9 promoter. Our results indicate that NCOA6 is responsible for the synergistic activation of CYP2C9 by HNF4α and PXR and NCOA6 differentially regulates CYP2C9 and CYP3A4 gene expression though both the genes are regulated by the same nuclear receptors.

Mid-Upper Arm Circumference Tapes and Measurement Discrepancies: Time to Standardize Product Specifications and Reporting.

In recent years, community-based management of acute malnutrition (CMAM) has revolutionized the care for children by increasing treatment coverage. Critical to the success of CMAM is early case identification. Mid-upper arm circumference (MUAC) measurement is a widely used, practical anthropometric measure used at the community level for the identification and admission of cases to appropriate treatment services. Globally, many organizations and government services use MUAC tapes for early case detection. However, there is no one universal MUAC tape specification, and it has been observed that using different MUAC tapes results in different measurements. In this article, we aim to: (1) present the measurement discrepancies; (2) discuss design specifications and their effect on case identification and admissions; (3) present a call to action to agree on common design specifications and standardized reporting. We hope this article will catalyze discussion and practical actions among nutrition and health stakeholders to ensure we have common MUAC tape design specifications so that all eligible at-risk children will get an equal chance to be identified early for critical treatment.

Effectiveness of Breastfeeding Support Packages in Low- and Middle-Income Countries for Infants under Six Months: A Systematic Review.

Small and nutritionally at-risk infants under six months, defined as those with wasting, underweight, or other forms of growth failure, are at high-risk of mortality and morbidity. The World Health Organisation 2013 guidelines on severe acute malnutrition highlight the need to effectively manage this vulnerable group, but programmatic challenges are widely reported. This review aims to inform future management strategies for small and nutritionally at-risk infants under six months in low- and middle-income countries (LMICs) by synthesising evidence on existing breastfeeding support packages for all infants under six months. We searched PubMed, CINAHL, Cochrane Library, EMBASE, and Global Health databases from inception to 18 July 2018. Intervention of interest were breastfeeding support packages. Studies reporting breastfeeding practices and/or caregivers'/healthcare staffs' knowledge/skills/practices for infants under six months from LMICs were included. Study quality was assessed using NICE quality appraisal checklist for intervention studies. A narrative data synthesis using the Synthesis Without Meta-analysis (SWiM) reporting guideline was conducted and key features of successful programmes identified. Of 15,256 studies initially identified, 41 were eligible for inclusion. They were geographically diverse, representing 22 LMICs. Interventions were mainly targeted at mother-infant pairs and only 7% (n = 3) studies included at-risk infants. Studies were rated to be of good or adequate quality. Twenty studies focused on hospital-based interventions, another 20 on community-based and one study compared both. Among all interventions, breastfeeding counselling (n = 6) and education (n = 6) support packages showed the most positive effect on breastfeeding practices followed by breastfeeding training (n = 4), promotion (n = 4) and peer support (n = 3). Breastfeeding education support (n = 3) also improved caregivers' knowledge/skills/practices. Identified breastfeeding support packages can serve as "primary prevention" interventions for all infants under six months in LMICs. For at-risk infants, these packages need to be adapted and formally tested in future studies. Future work should also examine impacts of breastfeeding support on anthropometry and morbidity outcomes. The review protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO 2018 CRD42018102795).

Malnutrition in Infants Aged under 6 Months Attending Community Health Centres: A Cross Sectional Survey.

A poor understanding of malnutrition burden is a common reason for not prioritizing the care of small and nutritionally at-risk infants aged under-six months (infants u6m). We aimed to estimate the anthropometric deficit prevalence in infants u6m attending health centres, using the Composite Index of Anthropometric Failure (CIAF), and to assess the overlap of different individual indicators. We undertook a two-week survey of all infants u6m visiting 18 health centres in two zones of the Oromia region, Ethiopia. We measured weight, length, and MUAC (mid-upper arm circumference) and calculated weight-for-length (WLZ), length-for-age (LAZ), and weight-for-age z-scores (WAZ). Overall, 21.7% (95% CI: 19.2; 24.3) of infants u6m presented CIAF, and of these, 10.7% (95% CI: 8.93; 12.7) had multiple anthropometric deficits. Low MUAC overlapped with 47.5% (95% CI: 38.0; 57.3), 43.8% (95% CI: 34.9; 53.1), and 42.6% (95% CI: 36.3; 49.2) of the stunted, wasted, and CIAF prevalence, respectively. Underweight overlapped with 63.4% (95% CI: 53.6; 72.2), 52.7% (95% CI: 43.4; 61.7), and 59.6% (95% CI: 53.1; 65.9) of the stunted, wasted, and CIAF prevalence, respectively. Anthropometric deficits, single and multiple, are prevalent in infants attending health centres. WAZ overlaps more with other forms of anthropometric deficits than MUAC.

Hepatocyte nuclear factor 4{alpha} regulates rifampicin-mediated induction of CYP2C genes in primary cultures of human hepatocytes.

CYP2C enzymes are expressed constitutively and comprise approximately 20% of the total cytochrome P450 in human liver. However, the factors influencing the transcriptional regulation of the CYP2C subfamily have only been addressed recently. In the present study, we used primary cultures of human hepatocytes to investigate the role of HNF4alpha in the pregnane X receptor (PXR)/rifampicin-mediated up-regulation of CYP2C8, CYP2C9, and CYP2C19 gene expression. We first identified new proximal cis-acting HNF4alpha sites in the proximal CYP2C8 promoter [at -181 base pairs (bp) from the translation start site] and the CYP2C9 promoter (at -211 bp). Both sites bound HNF4alpha in gel shift assays. Thus, these and recent studies identified a total of three HNF4alpha sites in the CYP2C9 promoter and two in the CYP2C8 promoter. Mutational studies showed that the HNF4alpha sites are needed for up-regulation of the CYP2C8 and CYP2C9 promoters by rifampicin. Furthermore, silencing of HNF4alpha abolished transactivation of the CYP2C8 and CYP2C9 promoters by rifampicin. Constitutive promoter activity was also decreased. Quantitative polymerase chain reaction analysis demonstrated that silencing HNF4alpha reduced the constitutive expression of CYP2C8 (53%), CYP2C9 (55%), and CYP2C19 (43%) mRNAs and significantly decreased the magnitude of the rifampicin-mediated induction of CYP2C8 (6.6- versus 2.7-fold), CYP2C9 (3- versus 1.5-fold), and CYP2C19 (1.8- versus 1.1-fold). These results provide clear evidence that HNF4alpha contributes to the constitutive expression of the human CYP2C genes and is also important for up-regulation by the PXR agonist rifampicin.

Feeding Interventions for Infants with Growth Failure in the First Six Months of Life: A Systematic Review.

(1) Introduction: Current evidence on managing infants under six months with growth failure or other nutrition-related risk is sparse and low quality. This review aims to inform research priorities to fill this evidence gap, focusing on breastfeeding practices. (2) Methods: We searched PubMed, CINAHL Plus, and Cochrane Library for studies on feeding interventions that aim to restore or improve the volume or quality of breastmilk and breastfeeding when breastfeeding practices are sub-optimal or prematurely stopped. We included studies from both low- and middle-income countries and high-income countries. (3) Results: Forty-seven studies met the inclusion criteria. Most were from high-income countries (n = 35, 74.5%) and included infants who were at risk of growth failure at birth (preterm infants/small for gestational age) and newborns with early growth faltering. Interventions included formula fortification or supplementation (n = 31, 66%), enteral feeds (n = 8, 17%), cup feeding (n = 2, 4.2%), and other (n = 6, 12.8%). Outcomes included anthropometric change (n = 40, 85.1%), reported feeding practices (n = 16, 34%), morbidity (n = 11, 23.4%), and mortality (n = 5, 10.6%). Of 31 studies that assessed formula fortification or supplementation, 30 reported anthropometric changes (n = 17 no effect, n = 9 positive, n = 4 mixed), seven morbidity (n = 3 no effect, n = 2 positive, n = 2 negative), five feeding (n = 2 positive, n = 2 no effect, n = 1 negative), and four mortality (n = 3 no effect, n = 1 negative). Of eight studies that assessed enteral feed interventions, seven reported anthropometric changes (n = 4 positive, n = 3 no effect), five feeding practices (n = 2 positive, n = 2 no effect, n = 1 negative), four morbidity (n = 4 no effect), and one reported mortality (n = 1 no effect). Overall, interventions with positive effects on feeding practices were cup feeding compared to bottle-feeding among preterm; nasogastric tube feed compared to bottle-feeding among low birth weight preterm; and early progressive feeding compared to delayed feeding among extremely low birth weight preterm. Bovine/cow milk feeding and high volume feeding interventions had an unfavourable effect, while electric breast pump and Galactagogue had a mixed effect. Regarding anthropometric outcomes, overall, macronutrient fortified formula, cream supplementation, and fortified human milk formula had a positive effect (weight gain) on preterm infants. Interventions comparing human breastmilk/donor milk with formula had mixed effects. Overall, only human milk compared to formula intervention had a positive effect on morbidity among preterm infants, while none of the interventions had any positive effect on mortality. Bovine/cow milk supplementation had unfavourable effects on both morbidity and mortality. (4) Conclusion: Future research should prioritise low- and middle-income countries, include infants presenting with growth failure in the post-neonatal period and record effects on morbidity and mortality outcomes.

Comparative evaluation of effects of natural antioxidants on the shear bond strength of composite resin to bleached enamel.

CONTEXT: The use of antioxidants immediately after bleaching showed increased bond strength. AIMS: This study aimed to compare the effects of natural antioxidants on the shear bond strength of composite resin to bleached enamel. MATERIALS AND METHODS: Fifty extracted single-rooted upper incisors were decoronated by sectioning the roots 2 mm below the cementoenamel junction, and then, crowns were embedded in autopolymerizing acrylic resin block (3.0 cm × 3.0 cm × 3.0 cm) with the labial surface exposed. They were randomly divided into five groups, depending on the type of antioxidant used (n = 10): (i) Group 1: control (no bleaching), (ii) Group 2: bleaching only, (iii) Group 3: bleaching + 10% sodium ascorbate (antioxidant), (iv) Group 4: bleaching + green tea, and (v) Group 5: bleaching + white tea. Labial surfaces of 40 teeth were bleached with 38% hydrogen peroxide for 20 min following manufacturer's instructions. After that, the experimental groups (Groups 3, 4, and 5) were treated with respective antioxidant solutions before composite restorations were done using a cylindrical plastic mold (3 mm × 5 mm). Shear bond strength of the specimens was tested under universal testing machine. STATISTICAL ANALYSIS: Data were analyzed with ANOVA and Tukey's post hoc test. RESULTS: There were statistically significant differences between shear bond strength of control groups (Groups 1 and 2) and experimental groups (P < 0.05), but no significant difference in bond strength was observed among the antioxidants used. CONCLUSION: Application of antioxidants immediately after bleaching showed increased bond strength. Green tea and white tea extract can be used as alternative antioxidants in improving the bond strength of enamel.