Prophylactic alpha-blockade for prevention of post-operative urinary retention after inguinal hernia repair: a systematic review and meta-analysis.

BACKGROUND: The rate of post-operative urinary retention (POUR) in inguinal hernia repairs (IHR) is estimated to be approximately 5.9% to 38% worldwide. Currently, there are minimal studies on the prophylaxis of POUR after IHR. Pre-operative administration of alpha-blockers such as (but not limited to) Tamsulosin, Prazosin and Alfuzosin has shown promising results in the prevention of POUR in patients undergoing IHR. This study aims to determine the effectiveness of prophylactic alpha-blockade in the prevention of POUR after IHR. METHODS: This study reports the findings of a systematic review and meta-analysis. Randomised controlled trials (RCTs) using prophylactic alpha-blockade for the prevention of POUR after open and/or laparoscopic IHR in patients aged more than 18 years in all sex groups were included. Multiple databases were searched from inception to October 2021 using the PRISMA flow diagram. Data were extracted and analysed to include eligibility criteria, comparator, intervention, study and participant characteristics. Studies excluded were non-RCT studies and patients with known urinary tract disorders such as benign prostate hypertrophy, urinary incontinence and cancer of the bladder or prostate. Subgroup analyses were also conducted. All effect measures of each data were odds ratio with 95% confidence interval. All studies were pooled using the dichotomous random effects Mantel-Haenszel statistical mode and I2 was used to assess heterogeneity. Publication bias was detected using the Cochrane risk-of-bias tool for randomised trials (RoB-2) involving two independent reviewers. RESULTS: A total of eight RCTs were identified which provided adequate numeric data for incorporation into the meta-analysis. Overall, administration of pre-operative alpha-blocker prior to IHR did not prevent POUR (95% CI 1.20 (0.96-1.49), I2: 34%). Subgroup analysis comparing pre-operative use of prophylactic alpha-blocker in open versus laparoscopic IHR has shown statistically significant reduction of POUR prevention in the laparoscopic group (95% CI 0.66 (0.47-0.92)), I2: 43%). The older age group benefited from pre-operative alpha-blocker use with reduced incidence of POUR post-IHR (95% CI 0.14 (0.08, 0.23), I2: 0%)). Gender did not affect the difference of incidence of POUR post-IHR despite pre-operative alpha-blockers (95% CI 0.62 (0.27, 1.44)), I2: 53%)). CONCLUSION: Overall, this meta-analysis has shown that administration of prophylactic alpha-blockers did not prevent POUR. However, there was statistically significant reduction of POUR in patients undergoing laparoscopic IHR as compared to open, as well as in older patients (age more than 60 years) after administration of pre-operative alpha-blocker. Hence, the use of pre-operative alpha-blocker especially in older patients should be considered and more RCTs should be undertaken.

Dragon 1 Protocol Manuscript: Training, Accreditation, Implementation and Safety Evaluation of Portal and Hepatic Vein Embolization (PVE/HVE) to Accelerate Future Liver Remnant (FLR) Hypertrophy.

STUDY PURPOSE: The DRAGON 1 trial aims to assess training, implementation, safety and feasibility of combined portal- and hepatic-vein embolization (PVE/HVE) to accelerate future liver remnant (FLR) hypertrophy in patients with borderline resectable colorectal cancer liver metastases. METHODS: The DRAGON 1 trial is a worldwide multicenter prospective single arm trial. The primary endpoint is a composite of the safety of PVE/HVE, 90-day mortality, and one year accrual monitoring of each participating center. Secondary endpoints include: feasibility of resection, the used PVE and HVE techniques, FLR-hypertrophy, liver function (subset of centers), overall survival, and disease-free survival. All complications after the PVE/HVE procedure are documented. Liver volumes will be measured at week 1 and if applicable at week 3 and 6 after PVE/HVE and follow-up visits will be held at 1, 3, 6, and 12 months after the resection. RESULTS: Not applicable. CONCLUSION: DRAGON 1 is a prospective trial to assess the safety and feasibility of PVE/HVE. Participating study centers will be trained, and procedures standardized using Work Instructions (WI) to prepare for the DRAGON 2 randomized controlled trial. Outcomes should reveal the accrual potential of centers, safety profile of combined PVE/HVE and the effect of FLR-hypertrophy induction by PVE/HVE in patients with CRLM and a small FLR. TRIAL REGISTRATION: Clinicaltrials.gov: NCT04272931 (February 17, 2020). Toestingonline.nl: NL71535.068.19 (September 20, 2019).

Collaborative health systems ECHO: The use of a tele-education platform to facilitate communication and collaboration with recipients of state targeted response funds in Pennsylvania.

Background: The opioid epidemic continues to erode communities across Pennsylvania (PA). Federal and PA state programs developed grants to establish Hub and Spoke programs for the expansion of medications for opioid use disorders (MOUD). Employing the telementoring platform Project ECHO (Extension for Community Health Outcomes), Penn State Health engaged the other seven grant awardees in a Collaborative Health Systems (CHS) ECHO. We conducted key informant interviews to better understand impact of the CHS ECHO on health systems collaboration and opioid crisis efforts. Methods: For eight one-hour sessions, each awardee presented their unique strategies, challenges, and opportunities. Using REDCap, program characteristics, such as number of waivered prescribers and number of patients served were collected at baseline. After completion of the sessions, key informant interviews were conducted to assess the impact of CHS ECHO on awardee's programs. Results: Analysis of key informant interviews revealed important themes to address opioid crisis efforts, including the need for strategic and proactive program reevaluation and the convenience of collaborative peer learning networks. Participants expressed benefits of the CHS ECHO including allowing space for discussion of challenges and best practices and facilitating conversation on collaborative targeted advocacy and systems-level improvements. Participants further reported bolstered motivation and confidence. Conclusions: Utilizing Project ECHO provided a bidirectional platform of learning and support that created important connections between institutions working to combat the opioid epidemic. CHS ECHO was a unique opportunity for productive and convenient peer learning across external partners. Open dialogue developed during CHS ECHO can continue to direct systems-levels improvements that benefit individual and population outcomes.

Sustained benefit of cognitive behaviour therapy for health anxiety in medical patients (CHAMP) over 8 years: a randomised-controlled trial.

BACKGROUND: Health anxiety is an under-recognised but a frequent cause of distress. It is particularly common in general hospitals. METHODS: We carried out an 8-year follow-up of medical out-patients with health anxiety (hypochondriasis) enrolled in a randomised-controlled trial in five general hospitals in London, Middlesex and Nottinghamshire. Randomisation was to a mean of six sessions of cognitive behaviour therapy adapted for health anxiety (CBT-HA) or to standard care in the clinics. The primary outcome was a change in score on the Short Health Anxiety Inventory, with generalised anxiety and depression as secondary outcomes. Of 444 patients aged 16-75 years seen in cardiology, endocrinology, gastroenterology, neurology and respiratory medicine clinics, 306 (68.9%) were followed-up 8 years after randomisation, including 36 who had died. The study is registered with controlled-trials.com, ISRCTN14565822. RESULTS: There was a significant difference in the HAI score in favour of CBT-HA over standard care after 8 years [1.83, 95% confidence interval (CI) 0.25-3.40, p = 0.023], between group differences in generalised anxiety were less (0.54, 95% CI -0.29 to 1.36), p = 0.20, ns), but those for depression were greater at 8 years (1.22, 95% CI 0.42-2.01, p < 0.003) in CBT-HA than in standard care, most in standard care satisfying the criteria for clinical depression. Those seen by nurse therapists and in cardiology and gastrointestinal clinics achieved the greatest gains with CBT-HA, with greater improvement in both symptoms and social function. CONCLUSIONS: CBT-HA is a highly long-term effective treatment for pathological health anxiety with long-term benefits. Standard care for health anxiety in medical clinics promotes depression. Nurse therapists are effective practitioners.

Quality of English inpatient mental health services for people with anxiety or depressive disorders: Findings and recommendations from the core audit of the National Clinical Audit of Anxiety and Depression.

BACKGROUND: Clinical audit is a sustained cyclical quality improvement process seeking to improve patient care and outcomes by evaluating services against explicit standards and implementing necessary changes. National audits aim to improve population-level clinical care by identifying unwarranted variations and making recommendations for clinicians, managers and service commissioners. The National Clinical Audit of Anxiety and Depression aimed to improve clinical care for people admitted to English hospitals for treatment of anxiety and depression, to provide comparative data on quality of care, and to support local quality improvement initiatives by identifying and sharing examples of best practice. PROCEDURES: Thirteen standards were developed based on NICE guidelines, literature review and feedback from a steering committee and reference group of service users and carers. All providers of NHS inpatient mental health services in England were asked to submit details of between 20 and 100 eligible service users/patients admitted between April 2017 and September 2018. To ascertain data reliability, participating services re-audited 5 sets of case-notes with a second auditor, and the coordinating team checked 10 randomly-selected sets of case-notes from 3 services, also selected at random. The reference group and steering committee identified key findings and developed a series of recommendations, which were discussed in regional quality improvement workshops and on-line webinars. FINDINGS: Data from 3795 case notes were analysed. A sizeable proportion of records indicated that at least one important aspect of initial assessment was not documented. Many service users/patients who could have benefited from an intervention targeted at optimising physical health did not receive it. Only a minority (39%) were referred for psychological therapy. Use of outcome measures varied considerably but no single outcome measure was being used routinely. Most individuals had a care plan recorded in the notes, but a review date was documented in only two-thirds, and almost half of individuals had not received a copy. CONCLUSIONS: There was considerable variation between English mental health services across many variables, and much scope for improvement. Clinicians should ensure that care plans are developed collaboratively with service users/patients and identified carers should be provided with information about support services. Health services should investigate the reasons for low referral rates for psychological therapies. Clinicians should ensure all service users have jointly developed crisis plans in place at discharge. Service managers should agree outcome measures to evaluate the treatment provided and clinicians should use these measures at initial assessment and review appointments. The implementation of such changes provides an opportunity for collaborative research into mental health service delivery and quality.

Brief psychological interventions for borderline personality disorder. A systematic review and meta-analysis of randomised controlled trials.

BACKGROUND: People with Borderline Personality Disorder (BPD) have limited access to long term psychological therapies. Briefer interventions have been developed but trial evidence to support their use has not been reviewed. AIMS: To examine whether psychological interventions for adults with BPD of six months duration or less improve symptoms, mood, self-harm, suicidal behaviour, and service use. METHODS: The protocol was prospectively registered (PROSPERO CRD42017063777). Database searches were conducted up to April 2020. Inclusion, data extraction and risk of bias were assessed in duplicate. We identified 27 randomised controlled trials. We conducted random-effects meta-analyses sub-grouping data into delivery method, additional support, and comparison type. RESULTS: High levels of bias were found for attrition and reporting. Heterogeneity was high in some pooled data. Borderline symptom reductions were greatest for interventions including additional support (SMD. -1.23, 95% C.I. -2.13, -0.33). Planned generic support may be as effective as specialist interventions for borderline symptoms (SMD = -0.11, 95% C.I. -0.51, 0.29) and social functioning (SMD = -0.16., 95% C.I. -0.65, 0.33). Follow-up was limited and direct comparison with post-intervention results was unreliable. CONCLUSIONS: Short-term interventions may be effective. Access to additional support has an impact on outcomes. It is unclear if symptomatic change is sustained.

Psychological interventions for acute psychiatric inpatients with schizophrenia-spectrum disorders: A systematic review and meta-analysis.

BACKGROUND: Acute inpatient psychiatric wards are important yet challenging environments in which to implement psychological interventions for people with schizophrenia-spectrum disorders. No meta-analysis to date has evaluated whether psychological interventions are effective in this context. METHODS: We systematically searched Embase, Medline and PsycInfo databases for randomised controlled trials (RCTs) of psychological interventions implemented in acute inpatient psychiatric settings with individuals with schizophrenia-spectrum disorders. We conducted random effects meta-analyses of between-groups outcomes at post-intervention and relapse/re-hospitalisation rates by follow-up. RESULTS: Twenty-nine trials were suitable for meta-analysis. Psychological interventions improved post-intervention positive symptoms, social functioning and treatment compliance and reduced the risk of relapse/ re-hospitalisation, relative to control conditions. Analyses of specific intervention effects found positive effects of psychoeducation on several key outcomes (power > 80%) and preliminary evidence for positive effects of acceptance and commitment therapy (ACT), cognitive behaviour therapy (CBT) and metacognitive training (MCT) on some outcomes (power < 80%). CONCLUSION: Psychological interventions can be helpful for acute inpatients with schizophrenia-spectrum disorders. However, risk of bias was often high or unclear, and some analyses were underpowered. Further research should use more rigorous RCT designs and publish meta-analysable data on positive symptoms, general psychopathology, relapse/ re-hospitalisation, social functioning and treatment compliance.

CITY Health II - using entertainment education and social media to reduce HIV among emerging adults: A protocol paper for the Beat HIVe project.

BACKGROUND: Despite multiple efforts to reduce HIV rates among African American young adults, a significant racial disparity persists and continues to grow among this population. New approaches are needed to reach this at-risk group and engage them in prevention efforts. The Community Influences Transitions of Youth Health (CITY Health II) study aims to increase HIV preventive behaviors to decrease HIV rates among 18-25 year old African American emerging adults living in resource-poor southern urban communities. METHODS: CITY Health II is a 5-year HIV prevention study that evaluates the efficacy of a peer-driven entertainment education intervention compared to an attention-control intervention using a cluster randomized trial design. Participants were recruited through respondent-driven sampling (RDS) to participate in a social media intervention. We enlisted eight musicians and groups to help us create an entertaining and educational web-based video series, "The Beat HIVe", for study participants to view on smartphones and share with peers on social media. Data collection interviews at baseline, 3-month, and 6-month follow-up assessed socio-demographics, risk and protective behaviors, social networks, and peer norms. Analyses will determine if participation is associated with improved HIV-related outcomes; examine whether intervention changes are mediated by perceived social norms and outcome expectations; determine whether intervention benefits vary by sociodemographic characteristics related to mediators, intervention outcome, or level of engagement; and examine the relationship between participant dose of intervention and outcomes. DISCUSSION: Outcomes will inform ways to engage African American emerging adults through entertainment education and other strategies for increasing optimal sexual health behaviors. TRIAL REGISTRATION: NCT04320186.

Novel Organic Mineral Complex Prevents High-Fat Diet-Induced Changes in the Gut and Liver of Male Sprague-Dawley Rats.

Diet-induced obesity and metabolic syndrome are associated with the onset of gastrointestinal diseases, such as hepatic steatosis and gut inflammation. Prior research shows that a proprietary soil-derived organic mineral complex (OMC) prevents hyperglycemia, endotoxemia, and liver injury in rats fed a high-fat diet (HFD) for 10 weeks. The aim of this study was to further examine the effects of OMC on the liver and gastrointestinal health of these rats. Six-week-old male Sprague-Dawley rats (n = 36) were divided into two dietary groups: Chow or HFD fed for 10 weeks. Animals were further divided (n = 6/group) and administered 0, 0.6, or 3.0 mg/mL OMC in their drinking water. The 10-week HFD resulted in significant liver fat accumulation. Both OMC doses prevented hepatic increases in the glycation end product Nε-(carboxymethyl)lysine (CML) induced by HFD (p < 0.05). Low-dose OMC was associated with higher expression of occludin in the small intestine of rats fed either diet (two-way ANOVA, p < 0.042). Linear discriminant analysis (LDA) effect size (LEfSe) indicated significant differences in fecal microbial composition of untreated HFD-fed rats in comparison to untreated Chow rats at 10 weeks (LDA score > 2.0 : 18). After 10 weeks, untreated HFD-fed rats were also more abundant in bacteria associated with obesity and metabolic disease in comparison to corresponding week 0 samples (LDA score > 2.0 : 31), 10-week untreated Chow (LDA > 2.0 : 18), or 10-week OMC-treated HFD-fed rats (0.6 mg/mL; LDA > 2.0 : 80, 3.0 mg/mL; LDA > 2.0 : 8). Low-dose OMC prevented the HFD-induced increase in the Firmicutes-to-Bacteroidetes (F/B) ratio (p < 0.0416). Study animals treated with OMC exhibited no significant changes in the gut microbiota at week 10, although gut inflammatory biomarkers were not significantly altered by diet or OMC treatment. These results indicate that OMC supplementation ameliorates glycosylation reactions and modifies HFD-induced alterations in the intestinal microbiota.

Patient-reported experience and quality of care for people with schizophrenia.

BACKGROUND: Evidence is mounting that patient-reported experience can provide a valuable indicator of the quality of healthcare services. However, little is known about the relationship between the experiences of people with severe mental illness and the quality of care they receive. We conducted a study to examine the relationship between patient-reported experience and the quality of care provided to people with schizophrenia. METHODS: We calculated a composite global rating of quality of care for people with schizophrenia using data from an audit of 64 mental health providers. We then examined associations between these ratings and mean patient satisfaction and patient-rated outcome using data from a survey of 5608 schizophrenic patients treated in these services. RESULTS: Global rating of quality of care was positively correlated with patient-rated outcome (r = 0.33; p = 0.01) but not with patient satisfaction (r = 0.21, p = 0.10). Patient-rated outcome was also positively correlated with patient involvement (r = 0.26, p = 0.04) and the quality of prescribing practice (r = 0.31, p = 0.02). High patient satisfaction scores were significantly associated with the extent of use of care plans within each organisation (r = 0.27, p = 0.03). CONCLUSIONS: Among people with schizophrenia, patient-rated outcome provides a better guide to the quality of care than patient-rated satisfaction. Greater use of patient-reported outcome measures should be made when assessing the quality of care provided to people with psychosis.

Randomized controlled trial of brain specific fatty acid supplementation in pregnant women increases brain volumes on MRI scans of their newborn infants.

Docosahexaenoic acid (DHA) and arachidonic acid (ArA) are essential brain specific fatty acids (BSFA) for mammalian central nervous system development. Human brains have accelerated growth with significant increase in cerebral content of ArA and DHA during the last trimester of pregnancy and first postnatal months. This randomized double blind placebo controlled single centre trial assessed the impact of BSFA supplementation in pregnancy on newborn infants' brain volumes. Eighty six infants born to study mothers had brain magnetic resonance imaging (MRI) scans soon after birth. Total and regional brain volumes were analyzed and related to maternal supplementation group. Males born to the BSFA supplemented mothers had significantly larger total brain volumes, total gray matter, corpus callosum and cortical volumes when compared to the placebo group. This is the first study to show maternal BSFA supplementation enhances newborn infants' brain size and suggests differential sex sensitivity of fetal brains to pregnancy BSFA status.

Hereditary haemorrhagic telangiectasia in pregnancy: regional and general anaesthesia.

Hereditary haemorrhagic telangiectasia, also known as Osler-Weber-Rendu disease, is a rare autosomal dominant multisystem disorder, characterised by mucocutaneous telangiectases and arteriovenous malformations affecting any organ. The physiological changes in pregnancy pose significant obstetric and anaesthetic challenges for women affected by the disease. The optimal timing and mode of delivery requires careful consideration; and the benefits and risks of both regional and general anaesthetic techniques must be carefully considered, depending on the organs affected. This case report describes the successful management of a patient with this disease and severe pulmonary involvement, who received both regional and general anaesthesia as a result of a complication in the initial anaesthetic plan. The report demonstrates the benefits of a multidisciplinary approach to a complex case, achieved through providing care in a tertiary centre with appropriate expertise and resources.

Classification of self-injurious behaviour across the continuum of relative environmental-biological influence.

Self-injurious behaviour (SIB) is generally considered to be the product of interactions between dysfunction stemming from the primary developmental disability and experiences that occasion and reinforce SIB. As a result of these complex interactions, SIB presents as a heterogeneous problem. Recent research delineating subtypes of SIB that are nonsocially mediated, including one that is amenable to change and one that is highly invariant, enables classification of SIB across a broader continuum of relative environmental-biological influence. Directly examining how the functional classes of SIB differ has the potential to structure research, will improve our understanding this problem, and lead to more targeted behavioural and pharmacological interventions. Recognising that SIB is not a single entity but is composed of distinct functional classes would better align research with conceptual models that view SIB as the product of interactions between environmental and biological variables.

Structures, Phase Transitions and Tricritical Behavior of the Hybrid Perovskite Methyl Ammonium Lead Iodide.

We have examined the crystal structures and structural phase transitions of the deuterated, partially deuterated and hydrogenous organic-inorganic hybrid perovskite methyl ammonium lead iodide (MAPbI3) using time-of-flight neutron and synchrotron X-ray powder diffraction. Near 330 K the high temperature cubic phases transformed to a body-centered tetragonal phase. The variation of the order parameter Q for this transition scaled with temperature T as Q ∼ (Tc-T)ß, where Tc is the critical temperature and the exponent ß was close to », as predicted for a tricritical phase transition. However, we also observed coexistence of the cubic and tetragonal phases over a range of temperature in all cases, demonstrating that the phase transition was in fact first-order, although still very close to tricritical. Upon cooling further, all the tetragonal phases transformed into a low temperature orthorhombic phase around 160 K, again via a first-order phase transition. Based upon these results, we discuss the impact of the structural phase transitions upon photovoltaic performance of MAPbI3 based solar cells.

Utility of Respondent Driven Sampling to Reach Disadvantaged Emerging Adults for Assessment of Substance Use, Weight, and Sexual Behaviors.

Emerging adulthood often entails heightened risk-taking with potential life-long consequences, and research on risk behaviors is needed to guide prevention programming, particularly in under-served and difficult to reach populations. This study evaluated the utility of Respondent Driven Sampling (RDS), a peer-driven methodology that corrects limitations of snowball sampling, to reach at-risk African American emerging adults from disadvantaged urban communities. Initial "seed" participants from the target group recruited peers, who then recruited their peers in an iterative process (110 males, 234 females; M age = 18.86 years). Structured field interviews assessed common health risk factors, including substance use, overweight/obesity, and sexual behaviors. Established gender-and age-related associations with risk factors were replicated, and sample risk profiles and prevalence estimates compared favorably with matched samples from representative U.S. national surveys. Findings supported the use of RDS as a sampling method and grassroots platform for research and prevention with community-dwelling risk groups.

Assessment of adult patients with chronic liver failure for liver transplantation in 2015: who and when?

In 2015, there are a few absolute contraindications to liver transplantation. In adult patients, survival post-liver transplant is excellent, with 1-year survival rate >90% and 5-year survival rates >80% and predicted median allograft survival beyond 20 years. Patients with a Child-Turcotte Pugh score ≥9 or a model for end-stage liver disease (MELD) score >15 should be referred for liver transplantation, with patients who have a MELD score >17 showing a 1-year survival benefit with liver transplantation. A careful selection of hepatocellular cancer patients results in excellent outcomes, while consideration of extra-hepatic disease (reversible vs irreversible) and social support structures are crucial to patient assessment. Alcoholic liver disease remains a challenge, and the potential to cure hepatitis C virus infection together with the emerging issue of non-alcoholic fatty liver disease-associated chronic liver failure will change the landscape of the who in the years ahead. The when will continue to be determined largely by the severity of liver disease based on the MELD score for the foreseeable future.

Patterns of DNA Methylation Across the Leptin Core Promoter in Four Diverse Asian and North American Populations.

DNA methylation is the most widely studied of epigenetic mechanisms, with environmental effects recorded through patterned attachments of methyl groups along the DNA that are capable of modifying gene expression without altering the DNA sequencing. The degree to which these patterns of DNA methylation are heritable, the expected range of normality across populations, and the phenotypic relevance of pattern variation remain unclear. Genes regulating metabolic pathways appear to be vulnerable to ongoing nutritional programming over the life course, as dietary nutrients are significant environmental determinants of DNA methylation, supplying both the methyl groups and energy to generate the methylation process. Here we examine methylation patterns along a region of the metabolic gene leptin (LEP). LEP's putative functions include regulation of energy homeostasis, with its signals affecting energy intake and expenditure, adipogenesis and energy storage, lipid and glucose metabolism, bone metabolism, and reproductive endocrine function. A pattern of differential methylation across CpG sites of the LEP core promoter has been previously identified; however, any consistency of pattern or its phenotypic significance is not fully elucidated among populations. Using DNA extracted from unfractionated white blood cells of peripheral blood samples, our pilot study, divided into two parts, examined the significance of variation in DNA methylation patterns along the leptin core promoter in four populations (phase 1) and used biomarkers reflecting leptin's functional process in two of those populations, western Buryat of Siberia and the Mennonite of central Kansas, to investigate the relevance of the ethnic variation identified in the DNA methylation (phase 2). LEP's core promoter region contains both the binding site for C/EBPα (CCAAT/enhancer binding protein alpha), which tempers the final step in adipocyte maturity and capacity to synthesize leptin, and the TATA motif controlling leptin synthesis. Previous studies report that increased methylation in this region is correlated to decreased gene expression, suggesting tissue-specific methylation variation at this region ( Melzner et al. 2002 ). We hypothesized that evidence of nutritional epigenetic programming would be identified through variation in patterns of DNA methylation and that functional relevance of that variation among populations would be identified through biomarkers that reflect leptin's metabolic signals: serum leptin levels, lipoproteins of the lipid transport system, and anthropometric measures. In phase 1, our combined analyses of 313 individuals documented a distinct and consistent overall pattern of differential DNA methylation across seven CpG sites of LEP core promoter in all ethnicities and both sexes. This pattern replicates those identified in previous studies, suggesting a conserved core promoter region across populations. Phase 2 analyses of two of the four populations (n = 239), correlating methylation at the C/EBPα transcription binding site (TBS) with metabolic and anthropometric biomarkers reflecting LEP roles, showed that stature, which reflects bone growth and remodeling, was significantly and inversely correlated with the percentage of DNA methylation at this site in both sexes. We suggest that variation in DNA methylation along the LEP core promoter plays a substantial role in energy signals affecting both adipogenesis and bone metabolism.