Incidence and outcomes of critical illness in indigenous peoples: a systematic review and meta-analysis.

BACKGROUND: Indigenous Peoples experience health inequities and racism across the continuum of health services. We performed a systematic review and meta-analysis of the incidence and outcomes of critical illness among Indigenous Peoples. METHODS: We searched Ovid MEDLINE/PubMed, Ovid EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials (inception to October 2022). Observational studies, case series of > 100 patients, clinical trial arms, and grey literature reports of Indigenous adults were eligible. We assessed risk of bias using the Newcastle-Ottawa Scale and appraised research quality from an Indigenous perspective using the Aboriginal and Torres Strait Islander Quality Assessment Tool. ICU mortality, ICU length of stay, and invasive mechanical ventilation (IMV) were compared using risk ratios and mean difference (MD) for dichotomous and continuous outcomes, respectively. ICU admission was synthesized descriptively. RESULTS: Fifteen studies (Australia and/or New Zealand [n = 12] and Canada [n = 3]) were included. Risk of bias was low in 10 studies and moderate in 5, and included studies had minimal incorporation of Indigenous perspectives or consultation. There was no difference in ICU mortality between Indigenous and non-Indigenous (RR 1.14, 95%CI 0.98 to 1.34, I2 = 87%). We observed a shorter ICU length of stay among Indigenous (MD - 0.25; 95%CI, - 0.49 to - 0.00; I2 = 95%) and a higher use for IMV among non-Indigenous (RR 1.10; 95%CI, 1.06 to 1.15; I2 = 81%). CONCLUSION: Research on Indigenous Peoples experience with critical care is poorly characterized and has rarely included Indigenous perspectives. ICU mortality between Indigenous and non-Indigenous populations was similar, while there was a shorter ICU length of stay and less mechanical ventilation use among Indigenous patients. Systematic Review Registration PROSPERO CRD42021254661; Registered: 12 June, 2021.

Incidence and outcomes of critical illness in Indigenous Peoples: a systematic review protocol.

BACKGROUND: Indigenous Peoples experience health inequities across the continuum of health services. Improvements for Indigenous patients and their families during vulnerable experiences with the healthcare system may have a significant impact on the patient experience and outcomes. Improved understanding of the occurrence of critical illness in Indigenous Peoples and their use of critical care services, as a strategic priority, may aid in the development of initiatives for improving health equity. A global focus was selected to learn from Indigenous populations' experiences with critical care, as the understanding of critical illness among Indigenous Peoples in Canada is not well understood. This protocol outlines a systematic review focused on describing the incidence of critical illness and utilization of critical care services among Indigenous Peoples. METHODS: Ovid MEDLINE/PubMed, Ovid EMBASE, Google Scholar, and Cochrane Central Register of Controlled Trials will be searched. Relevant Canadian sites for gray literature (National Collaborating Centre for Indigenous Health, First Nations Health Authority, Canadian Institutes of Health Research Institute of Indigenous Peoples' Health, National Association of Friendship Centres, the Alberta First Nations Information Governance Centre, Métis Nation of Alberta) will also be searched. We will include studies of adults (≥18 years) either without critical illness (i.e., general population) or with critical illness (i.e., admitted to an intensive care unit (ICU)). The exposure of interest will be Indigenous identity. Primary outcome measures are ICU admission and ICU mortality. Because heterogeneity in populations, comparisons, and outcome measures is anticipated, it is likely that the findings will be summarized using a narrative synthesis. A meta-analysis will be performed if there is sufficient evidence on one or more outcomes of interest. DISCUSSION: This systematic review will provide a better understanding of the epidemiology, risk factors, and outcomes of critical illness and utilization of critical care services among Indigenous Peoples. The knowledge generated will be applied to a broader program of work designed to create ethical space to co-design, implement, and evaluate a culturally competent, safe, and innovative model for critical care services for Indigenous People. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42021254661.

Methionine synthase deficiency: Variable clinical presentation and benefit of early diagnosis and treatment.

Methionine synthase deficiency (cblG complementation group) is a rare inborn error of metabolism affecting the homocysteine re-methylation pathway. It leads to a biochemical phenotype of hyperhomocysteinemia and hypomethioninemia. The clinical presentation of cblG is variable, ranging from seizures, encephalopathy, macrocytic anemia, hypotonia, and feeding difficulties in the neonatal period to onset of psychiatric symptoms or acute neurologic changes in adolescence or adulthood. Given the variable and nonspecific symptoms seen in cblG, the diagnosis of affected patients is often delayed. Medical management of cblG includes the use of hydroxocobalamin, betaine, folinic acid, and in some cases methionine supplementation. Treatment has been shown to lead to improvement in the biochemical profile of affected patients, with lowering of total homocysteine levels and increasing methionine levels. However, the published literature contains differing conclusions on whether treatment is effective in changing the natural history of the disease. Herein, we present five patients with cblG who have shown substantial clinical benefit from treatment with objective improvement in their neurologic outcomes. We demonstrate more favorable outcomes in our patients who were treated early in life, especially those who were treated before neurologic symptoms manifested. Given improved outcomes from treatment of presymptomatic patients, cblG warrants inclusion in newborn screening.

Mandatory newborn screening in the United States: History, current status, and existential challenges.

Beginning in the 1960s, mandatory newborn screening (NBS) of essentially all infants has been a major public health success story. NBS is not just a blood test, rather, it is a complex, integrated system that begins with timely testing, scrupulous follow up of patients, tracking of outcomes, quality improvement of all aspects of the process, and education of providers, staff, and parents. In the past, expansion of NBS programs has been driven by new testing technology, but now is increasingly driven by the development of novel therapeutics and political advocacy. Each state determines how the NBS system will be structured in that state, but there is increasing oversight and support for harmonization at a federal level. Several recent initiatives, together with the increased number of conditions screened and the concomitant increase in burdensome false-positive tests, are creating new scrutiny of NBS systems, and potentially pose an existential risk to the public acceptance of mandatory NBS. The history, current state and challenges for NBS are explored in this issue, with some suggestions as to how to address them.

Neonatal Macrosomia is an Interfering Factor for Analytes on the Colorado State Newborn Screen.

PURPOSE: Neonatal macrosomia is a known complication of maternal obesity and gestational diabetes, and it is a risk factor for obesity and diabetes in offspring. Amino acids and acylcarnitines are biomarkers for obesity in children and adults. These analytes, which are also routinely obtained on the newborn screen, have not been well-characterized in macrosomic newborns. The impact of macrosomia on rates of false-positive results in the newborn screen has also not been well-studied. We test the hypothesis that macrosomia is an interfering factor for amino acids and/or acylcarnitines on the newborn screen. METHODS: Newborn screening analytes determined by tandem mass spectroscopy were obtained from the Colorado Department of Public Health and Environment archives (2016-2018). This included metabolite concentrations obtained at 24-72 hours of life from newborns with birth weight 2500 to 3999 g (nonmacrosomic, n = 131 896) versus 4000 to 8000 g (macrosomic, n = 7806). Mother/infant phenotypic data were limited to information provided on the newborn screening dried blood spot card. Data were analyzed using Student t-test and chi-squared analysis. RESULTS: Macrosomic newborns had elevations in C2, C3, dicarboxylic, and long-chain acylcarnitines (specifically C16 and C18 species). C3 and C18:1 were 2 to 3 times more likely to be above predetermined state cutoffs in macrosomic versus nonmacrosomic newborns (both male and female). MAIN CONCLUSIONS: Macrosomia is an interfering factor for the analytes C3 and C18:1, leading to higher risk of false-positive results for methylmalonic/propionic acidemia and carnitine palmitoyl transferase type 2 deficiency, respectively. Analyte patterns found in macrosomic neonates correspond with similar analyte patterns in obese children and adults.

The use of psychiatry-focused simulation in undergraduate nursing education: A systematic search and review.

Evidence on the use of simulation to teach psychiatry and mental health (including addiction) content is emerging, yet no summary of the implementation processes or associated outcomes exists. The aim of this study was to systematically search and review empirical literature on the use of psychiatry-focused simulation in undergraduate nursing education. Objectives were to (i) assess the methodological quality of existing evidence on the use of simulation to teach mental health content to undergraduate nursing students, (ii) describe the operationalization of the simulations, and (iii) summarize the associated quantitative and qualitative outcomes. We conducted online database (MEDLINE, Embase, ERIC, CINAHL, PsycINFO from January 2004 to October 2015) and grey literature searches. Thirty-two simulation studies were identified describing and evaluating six types of simulations (standardized patients, audio simulations, high-fidelity simulators, virtual world, multimodal, and tabletop). Overall, 2724 participants were included in the studies. Studies reflected a limited number of intervention designs, and outcomes were evaluated with qualitative and quantitative methods incorporating a variety of tools. Results indicated that simulation was effective in reducing student anxiety and improving their knowledge, empathy, communication, and confidence. The summarized qualitative findings all supported the benefit of simulation; however, more research is needed to assess the comparative effectiveness of the types of simulations. Recommendations from the findings include the development of guidelines for educators to deliver each simulation component (briefing, active simulation, debriefing). Finally, consensus around appropriate training of facilitators is needed, as is consistent and agreed upon simulation terminology.

Experiences of midwives and nurses in policy development in low- and middle-income countries: a systematic review protocol.

REVIEW QUESTION/OBJECTIVE: The objective of this review is to identify, appraise and synthesize the qualitative evidence on the experiences of midwives' and nurses' involvement in policy development in low- and middle-income countries (LMICs). This qualitative review seeks to address the following question:What are midwives' and nurses' experiences of being involved in policy development in LMICs?

Eliciting women's cervical screening preferences: a mixed methods systematic review protocol.

BACKGROUND: With the accumulation of evidence regarding potential harms of cancer screening in recent years, researchers, policy-makers, and the public are becoming more critical of population-based cancer screening. Consequently, a high-quality cancer screening program should consider individuals' values and preferences when determining recommendations. In cervical cancer screening, offering women autonomy is considered a "person-centered" approach to health care services; however, it may impact the effectiveness of the program should women choose to not participate. As part of a larger project to investigate women's cervical screening preferences and correlates of these preferences, this systematic review will capture quantitative and qualitative investigations of women's cervical screening preferences and the methods used to elicit them. DESIGN AND METHODS: This mixed methods synthesis will use a thematic analysis approach to synthesize qualitative, quantitative, and mixed methods evidence. This protocol describes the methods that will be used in this investigation. A search strategy has been developed with a health librarian and peer reviewed using PRESS. Based on this strategy, five databases and the gray literature will be searched for studies that meet the inclusion criteria. The quality of the included individual studies will be examined using the Mixed Methods Appraisal Tool. Three reviewers will extract data from the primary studies on the tools or instruments used to elicit women's preferences regarding cervical cancer screening, theoretical frameworks used, outcomes measured, the outstanding themes from quantitative and qualitative evidence, and the identified preferences for cervical cancer screening. We will describe the relationships between study results and the study population, "intervention" (e.g., tool or instrument), and context. We will follow the PRISMA reporting guideline. We will compare findings across studies and between study methods (e.g., qualitative versus quantitative study designs). The strength of the synthesized findings will be assessed using the validated GRADE and CERQual tool. DISCUSSION: This review will inform the development of a tool to elicit women's cervical screening preferences. Understanding the methods used to elicit women's preferences and what is known about women's cervical screening preferences will be useful for guideline developers who wish to incorporate a woman-centered approach specifically for cervical screening guidelines. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42016035737.

Corrigendum: Increasing Prevalence of Type 2 Diabetes in a Rural Bangladeshi Population: A Population Based Study for 10 Years.

[This corrects the article on p. 46 in vol. 37, PMID: 23439676.].

Comparison of the prevalence of metabolic syndrome and its association with diabetes and cardiovascular disease in the rural population of Bangladesh using the modified National Cholesterol Education Program Expert Panel Adult Treatment Panel III and International Diabetes Federation definitions.

AIMS/INTRODUCTION: To compare the prevalence of metabolic syndrome (MS) using the modified National Cholesterol Education Program Adult Treatment Plan III (NCEP) and the International Diabetes Federation (IDF) definitions and, using both definitions, determine and compare the association of MS, prediabetes, type 2 diabetes, hypertension (HTN) and cardiovascular disease risk (CVD). MATERIALS AND METHODS: A total of 2,293 randomly selected participants (aged ≥20 years) in a rural community in Bangladesh were investigated in a population-based cross-sectional study. Sociodemographic and anthropometric characteristics, blood pressure, blood glucose, and lipid profiles were studied. Age-adjusted data for MS and cardiometabolic risk factors were assessed, and their relationships were examined. RESULTS: The age-adjusted prevalence of MS was 30.7% (males 30.5%; females 30.5%) using the NCEP definition, and 24.5% (males 19.2%, females 27.5%) using the IDF definition. The prevalence of MS using the NCEP definition was also higher in study participants with prediabetes, type 2 diabetes, HTN and CVD risk. The agreement rate between both definitions was 92% (k = 0.80). The NCEP definition had a stronger association with type 2 diabetes and HTN (odds ratio 12.4 vs 5.2; odds ratio 7.0 vs 4.7, respectively) than the IDF definition. However, the odds ratios for prediabetes and CVD risk were not significantly different. CONCLUSIONS: The prevalence of MS was higher using the NCEP definition, and was more strongly associated with prediabetes, type 2 diabetes, HTN and CVD in this Bangladeshi population.

Workplace physical activity interventions and moderate-to-vigorous intensity physical activity levels among working-age women: a systematic review protocol.

BACKGROUND: The rapid pace of modern life requires working-age women to juggle occupational, family and social demands. This modern lifestyle has been shown to have a detrimental effect on health, often associated with increased smoking and alcohol consumption, depression and cardiovascular disease risk factors. Despite the proven benefits of regular moderate-to-vigorous intensity physical activity (MVPA), few are meeting the current physical activity (PA) recommendations of 150 min of MVPA/week. It is important that appropriate and effective behavioural interventions targeting PA are developed and identified to improve the MVPA levels of working-age women. As these women spend a substantial proportion of their waking hours at work, workplaces may be an opportune, efficient and relatively controlled setting to implement programmes and strategies to target PA in an effort to improve MVPA levels and impact cardiometabolic health. The purposes of this systematic review are to compare the effectiveness of individual-level workplace interventions for increasing MVPA levels in working-age women in high-income/developed countries and examine the effectiveness of these interventions for improving the known beneficial health sequelae of MVPA. METHODS/DESIGN: Eight electronic databases will be searched to identify all prospective cohort and experimental studies that examine the impact of individual-level workplace interventions for increasing MVPA levels among working-age (mean age 18-65 years) women from high-income/developed countries. Grey literature including theses, dissertations and government reports will also be included. Study quality will be assessed using a modified Downs and Black checklist, and risk of bias will be assessed within and across all included studies using the Cochrane's risk of bias tool and Grades of Recommendation, Assessment, Development and Evaluation approach. Meta-analyses will be conducted where possible among studies with sufficient homogeneity. DISCUSSION: This review will determine the effectiveness of individual-level workplace interventions for increasing MVPA levels in working-age women in high-income/developed countries, and form a current, rigorous and reliable research base for policy makers and stakeholders to support the development and implementation of effective workplace interventions that increase MVPA levels in this population. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009704.

Intrapersonal, social and physical environmental determinants of moderate-to-vigorous physical activity in working-age women: a systematic review protocol.

BACKGROUND: The majority of North American adult females do not meet current physical activity recommendations (150 min of moderate-to-vigorous intensity physical activity (MVPA) per week accrued in ≥10 min bouts) ultimately placing themselves at increased risk of morbidity and mortality. Working-age females face particular challenges in meeting physical activity recommendations as they have multiple demands, including occupational, family and social demands. To develop effective interventions to increase MVPA among working-age females, it is necessary to identify and understand the strongest modifiable determinants influencing these behaviours. Therefore, the objective of this systematic review is to examine the available evidence to identify intrapersonal, social and environmental determinants of MVPA among working-age females. METHODS/DESIGN: Six electronic databases will be searched to identify all prospective cohort studies that report on intrapersonal, social and/or environmental determinants of MVPA in working-age females. Grey literature sources including theses, published conference abstracts and websites from relevant organizations will also be included. Articles that report on intrapersonal (e.g. health status, self-efficacy, socio-economic status (SES), stress, depression), social environmental (e.g. crime, safety, area SES, social support, climate and capital, policies), and environmental (e.g. weather, workplace, home, neighbourhood, recreation environment, active transportation) determinants of MVPA in a working-age (mean age 18-65 years) female population will be included. Risk of bias will be assessed within and across all included studies using the Tool to Assess Risk of Bias in Cohort Studies and the Grades of Recommendation, Assessment, Development and Evaluation approach. Harvest plots will be used to synthesize results across all determinants, and meta-analyses will be conducted where possible among studies with sufficient homogeneity. DISCUSSION: This review will provide a comprehensive examination of evidence in this field and will serve to highlight gaps for future research on the determinants of MVPA in working-age females and ultimately inform intervention design. SYSTEMATIC REVIEW REGISTRATION PROSPERO: CRD42014009750.

Individual, social and physical environmental correlates of sedentary behaviours in adults: a systematic review protocol.

BACKGROUND: Adults spend the majority of their time being sedentary, and evidence suggests that those who spend more of their day engaged in sedentary activities (TV viewing, sitting, screen-based activities) are at increased risk for morbidity and mortality, regardless of whether they exercise regularly. In order to develop effective interventions to reduce sedentary time, it is necessary to identify and understand the strongest modifiable factors of these behaviours. Therefore, the objective of this systematic review is to examine the available evidence in order to identify individual, social, environmental and policy correlates and determinants of sedentary behaviours (TV time, sitting time, screen time) and total sedentary time among adults. METHODS/DESIGN: Six electronic databases will be searched to identify all studies that report on individual, social and/or environmental correlates and determinants of sedentary behaviours and total sedentary time in adults. Grey literature sources including theses, published conference abstracts and websites from relevant organizations will also be included. Articles that report on modifiable individual (e.g. health behaviours and status, self-efficacy, socio-economic status), social (e.g. crime, safety, social support, climate and capital), environmental (e.g. weather, workplace, home, neighbourhood, recreation environment, transportation environment) and policy correlates and determinants (based on study design) of sedentary behaviours in an adult population (mean age ≥18 years) will be included. Study quality and risk of bias will be assessed within and across all included studies. Harvest plots will be used to synthesize results across all correlates, and meta-analyses will be conducted where possible among studies with sufficient homogeneity. DISCUSSION: This review will provide a comprehensive examination of evidence in the field and will serve to highlight gaps for future research on the determinants of sedentary behaviours and inform intervention design. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42014009814.

Anthropometric indices of obesity and type 2 diabetes in Bangladeshi population: Chandra Rural Diabetes Study (CRDS).

BACKGROUND: Obesity is a risk factor for type 2 diabetes (DM); however, no study has specially assessed the anthropometric indices as predictors of diabetes in rural Bangladeshi population. OBJECTIVE: To identify markers for diabetes through body mass index (BMI), waist circumference (WC), waist hip ratio (WHR) and waist height ratio (WHtR) and identify the optimal cut-off values suitable for Bangladeshi adult population. METHODS: A total of 2293 subjects aged ≥20 years from rural Bangladesh were randomly recruited to participate in a population-based, cross sectional survey. Age adjusted data for anthropometric indices and diabetes risk were assessed and their relationships were examined. RESULTS: Age adjusted prevalence of DM in men and women were 9.5% and 7.0%, respectively. Both men and women with DM had a higher rate of general obesity (defined by BMI) and central obesity (defined by WC, WHR and WHtR) than non-diabetic subjects. In both men and women the most sensitive indice was WHR for predicting DM. The appropriate cut-offs values for WHR to predict DM in men and women were 0.93 and 0.87, respectively. WC of 82 cm for both sexes was appropriate to predict DM. Those of BMI and WHtR were 21.2 kg/m2, 21.8 kg/m2 and 0.53, 0.54 in men and women, respectively. CONCLUSIONS: Compared with BMI, measures of central obesity, WHR, WC, WHtR showed a better association with the risk of DM for both sexes in rural Bangladeshi population. Follow-up studies are needed for validifying these cut-offs values.

Increasing prevalence of type 2 diabetes in a rural bangladeshi population: a population based study for 10 years.

BACKGROUND: To observe changes in the prevalence of type 2 diabetes mellitus (DM) and impaired fasting glucose (IFG) and its associated risk factors in a rural Bangladeshi population over a 10-year period. METHODS: Three cross-sectional studies were undertaken in a rural community (aged ≥20 years) in 1999, 2004, and 2009. Structured questionnaires including sociodemographic parameters, anthropometric measurements, blood pressure, and blood glucose values were recorded. DM and IFG were diagnosed using 1999 World Health Organization criteria. RESULTS: Age standardized prevalence of DM increased significantly (P<0.001) from 1999 to 2009 (2.3%, 6.8%, and 7.9% in 1999, 2004, and 2009, respectively). The prevalence of IFG increased significantly (P=0.011) from 4.6% to 5.8% between 1999 and 2004 but then decreased from 5.8% to 5.3% during 2004 to 2009. Significant linear trends were shown in both sexes for general and central obesity as indicated by body mass index, waist circumference, and waist hip ratio (WHR). Increasing age and systolic blood pressure were significant risk factors for DM in all three studies. WHR for males was also significantly associated with the risk of DM in all three studies. WHR for females was only significantly associated with DM in 2009. CONCLUSION: A significant rise in the prevalence of DM was observed in this population over 10 years. This increase was seen in both sexes, and in all age groups. A significant increase in the prevalence of the associated risk factors of general and central obesity was observed in both sexes.

Outcome of infants diagnosed with 3-methyl-crotonyl-CoA-carboxylase deficiency by newborn screening.

INTRODUCTION: 3-Methyl CoA carboxylase (3-MCC) deficiency is an inborn error of metabolism in the catabolism of the amino acid leucine. Original reports suggested this disorder was associated with significant neurological and biochemical effects. However newborn screening has identified a higher than expected incidence of this disorder with apparent normal outcome in most cases. METHOD: A retrospective analysis of thirty-five cases of 3-MCC deficiency identified by newborn screening and diagnosed by enzyme or molecular analysis. RESULTS: There was a strong inverse correlation between initial C5OH level and residual enzyme activity. A few reports of hypoglycemia, ketosis, poor feeding/failure to thrive or fasting intolerance were reported, but there was no clear relationship between symptoms and residual enzyme activity. Developmental outcome included several children with mental retardation (including one with Down syndrome and one with schizencephaly) and two with Autism Spectrum disorders but there was no apparent relationship to residual enzyme activity. Free carnitine deficiency was relatively common. DISCUSSION: Although residual enzyme activity was clearly related to metabolite elevation, there was no apparent relationship with other measures of outcome. The number of reports of neurologic abnormalities or metabolic symptoms (poor feeding, hypoglycemia, fasting intolerance, etc.) is concerning, but the significance is unclear in this retrospective sample.

Mountain States Genetics Regional Collaborative Center's Metabolic Newborn Screening Long-term Follow-up Study: a collaborative multi-site approach to newborn screening outcomes research.

PURPOSE: This article presents the rationale and design of the Mountain States Genetics Regional Collaborative Center's Metabolic Newborn Screening Long-Term Follow-up Study. METHODS: This study is a collaboration of multi-site metabolic providers throughout the Mountain States region investigating the long-term outcomes of individuals with metabolic conditions detected by newborn screening. RESULTS: The Mountain States Genetics Regional Collaborative Center's Metabolic Consortium developed disease-specific care plans that included baseline and follow-up datasets for all metabolic disorders detected by both standard and tandem mass spectrometry newborn screening. CONCLUSION: These disease-specific care plans are used at multiple metabolic clinics throughout the Mountain States region. The shared datasets consisting of both performance and outcome indicators will be used to explore questions related to the treatment and outcome of these rare metabolic disorders. They will be used to assess the impact of newborn screening by comparing those individuals detected by newborn screening with those individuals diagnosed clinically, therefore allowing the systematic investigation of factors that impact long-term outcome.

Positive newborn screen for methylmalonic aciduria identifies the first mutation in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12).

Elevated methylmalonic acid in five asymptomatic newborns whose fibroblasts showed decreased uptake of transcobalamin-bound cobalamin (holo-TC), suggested a defect in the cellular uptake of cobalamin. Analysis of TCblR/CD320, the gene for the receptor for cellular uptake of holo-TC, identified a homozygous single codon deletion, c.262_264GAG (p.E88del), resulting in the loss of a glutamic acid residue in the low-density lipoprotein receptor type A-like domain. Inserting the codon by site-directed mutagenesis fully restored TCblR function.