Human milk, breastfeeding, and early neurodevelopmental outcomes for infants with critical CHD.

Human milk improves neurodevelopment for preterm infants, but relationships between human milk and neurodevelopment for infants with critical CHD are unknown. We aimed to (1) explore associations between human milk/direct breastfeeding and neurodevelopment at 1-year and 2-year follow-up and (2) describe patterns of human milk (maternal, donor) and commercial formula during hospitalisation in the first year of life.This retrospective cohort study included infants who underwent surgery for CHD < 6 months old. The primary outcome was neurodevelopment via Bayley Scales of Infant Development-IV. Analysis included adjusted linear regression for associations between exclusive human milk while inpatient during the first 6 months or any direct breastfeeding while inpatient during the first year of life and 1-year Bayley-IV scores. Models were adjusted for race, insurance type, genetic diagnosis, and length of stay.Of 98 eligible infants, 40% followed up at 1 year; 27% at 2 years. There were differences in follow-up related to demographics (race, ethnicity) and social determinants of health (insurance type, distance from clinic). In adjusted models, infants who directly breastfed had 13.18 points higher cognition (95% CI: 0.84-25.53, p = 0.037); 14.04 points higher language (2.55-25.53, p = 0.018); and 15.80 points higher motor scores (3.27-28.34, p = 0.015) at 1-year follow-up. Infants fed exclusive human milk had 12.64 points higher cognition scores (-0.53-25.82, p = 0.059).Future investigation into nutrition and neurodevelopment in the context of critical CHD is warranted. As neurodevelopmental follow-up becomes standard of care in this population, efforts are needed to mitigate disparities in access to this care.

Neonatal Diet Type and Associations With Adverse Feeding Outcomes in Neonates With Critical Congenital Heart Defects.

BACKGROUND: Neonates with critical congenital heart defects (CCHD neonates) experience high rates of feeding intolerance, necrotizing enterocolitis (NEC), and malnutrition. The benefits of human milk and direct chest/breastfeeding are well known, but research is limited in CCHD neonates. Therefore, the purpose of this study is to examine the impact of neonatal diet and feeding modality on the incidence of feeding intolerance, NEC, and malnutrition among a cohort of CCHD neonates. METHODS: A single-center retrospective study was conducted using electronic health record data of CCHD neonates admitted to a cardiac intensive care unit between April 2016 and April 2020. Regression models were fit to analyze associations between neonatal diet, feed modality, and adverse feeding outcomes. RESULTS: Seventy-four CCHD neonates were included. Increased days of direct chest/breastfeeding were associated with fewer signs of gastrointestinal distress ( P = .047) and bloody stools ( P = .021). Enteral feeding days of "all human milk" were associated with higher growth trajectory ( P < .001). CONCLUSIONS: Human milk and direct chest/breastfeeding may be protective against some adverse feeding outcomes for CCHD neonates. Larger, multicenter cohort studies are needed to continue investigating the effects of neonatal diet type and feeding modality on the development of adverse feeding outcomes in this unique population.

Urinary sodium concentration predicts time to major adverse coronary events and all-cause mortality in men with heart failure over a 28-33-year period: a prospective cohort study.

BACKGROUND: Lower urinary sodium concentrations (UNa) may be a biomarker for poor prognosis in chronic heart failure (HF). However, no data exist to determine its prognostic association over the long-term. We investigated whether UNa predicted major adverse coronary events (MACE) and all-cause mortality over 28-33 years. METHODS: One hundred and eighty men with chronic HF from the Kuopio Ischaemic Heart Disease Risk Factor Study (KIHD) were included. Baseline data was collected between 1984 and 1989. MACE and all-cause outcomes were obtained using hospital linkage data (1984-2017) with a follow-up of 28-33 years. Cox proportional hazards models were generated using 24-h UNa tertiles at baseline (1 ≤ 173 mmol/day; 2 = 173-229 mmol/day; 3 = 230-491 mmol/day) as a predictor of time-to-MACE outcomes, adjusted for relevant covariates. RESULTS: Overall, 63% and 83% of participants (n = 114 and n = 150) had a MACE event (median 10 years) and all-cause mortality event (median 19 years), respectively. On multivariable Cox Model, relative to the lowest UNa tertile, no significant difference was noted in MACE outcome for individuals in tertiles 2 and 3 with events rates of 28% (HR:0.72; 95% CI: 0.46-1.12) and 21% (HR 0.79; 95% CI: 0.5-1.25) respectively.. Relative to the lowest UNa tertile, those in tertile 2 and 3 were 39% (HR: 0.61; 95% CIs: 0.41, 0.91) and 10% (HR: 0.90; 95% CIs: 0.62, 1.33) less likely to experience to experience all-cause mortality. The multivariable Cox model had acceptable prediction precision (Harrell's C concordance measure 0.72). CONCLUSION: UNa was a significant predictor of all-cause mortality but not MACE outcomes over 28-33 years with 173-229 mmol/day appearing to be the optimal level. UNa may represent an emerging long-term prognostic biomarker that warrants further investigation.

First Feed Type Is Associated With Birth/Lactating Parent's Own Milk Use During NICU Stay Among Infants Who Require Surgery.

BACKGROUND: Early exclusive birth/lactating parent's own milk (B/LPOM) feeds have been associated with longer duration of B/LPOM use for infant feedings in healthy term and hospitalized preterm infants. This relationship has not been explored in infants undergoing neonatal surgery (surgical infants). PURPOSE: To evaluate the relationship between early exclusive B/LPOM feeds and cumulative B/LPOM patterns during surgical infants' neonatal intensive care unit (NICU) hospitalization. METHODS: A secondary cross-sectional analysis was performed using the electronic health record data of surgical infants admitted to a level IV NICU between January 2014 and March 2015. Multiple linear regression and Fisher's exact test were used to examine the associations between first NICU feed type and total percentage of diet composed of B/LPOM during NICU stay and continuation of any or exclusive B/LPOM feedings at NICU discharge, respectively. RESULTS: The analysis included 59 infants who required surgery for gastrointestinal, cardiac, or multisystem defects or pregnancy-related complications. Receipt of B/LPOM as the first NICU feed was associated with higher percentage of B/LPOM feeds ( P < .001) throughout NICU stay, as well as continuation of any or exclusive B/LPOM feedings at NICU discharge ( P = .03). IMPLICATIONS FOR PRACTICE: Early exclusive B/LPOM feeds may be an important predictor for continuation of any B/LPOM use throughout the NICU stay and at NICU discharge. Continued efforts to identify and address gaps in prenatal and postpartum lactation support for parents of surgical infants are needed. IMPLICATIONS FOR RESEARCH: Powered studies are needed to corroborate these findings and to explore the potential impact of other factors on duration and exclusivity of B/LPOM use. VIDEO ABSTRACT AVAILABLE AT: https://journals.lww.com/advancesinneonatalcare/Pages/videogallery.aspx .

Antenatal Milk Expression as a Lactation Support Intervention for Parents of Infants With Severe Birth Defects: A Case Series.

BACKGROUND: A diet high in parent's own milk (parental milk) is a lifesaving intervention for critically ill infants. Lactating parents whose infants are born with birth defects that require surgical repair (surgical infants) shortly after birth often struggle to initiate and maintain a milk supply that meets their infant's nutritional needs. Antenatal milk expression has been identified as a safe, feasible, and potentially effective strategy that promotes parents' direct chest/breastfeeding or milk expression (lactation) confidence and helps parents attain their lactation goals. Two cases are presented to illustrate the potential for using antenatal milk expression as a lactation support intervention for parents of surgical infants. CASE PRESENTATION: Cases were drawn from a pilot study exploring the feasibility of implementing antenatal milk expression among pregnant parents of surgical infants. Participants were healthy women recruited after 30 weeks of gestation who received a fetal diagnosis of a complex congenital heart defect. Despite variability in clinical course and length of stay, parental milk was provided for the duration of each infant's hospitalization. Participant perceptions of antenatal milk expression varied. CONCLUSION: More research is needed to evaluate the feasibility, efficacy, and parent or provider perceptions of antenatal milk expression as a lactation support intervention for parents of surgical infants.

Gut Microbiome Diversity and Composition Are Associated with Habitual Dairy Intakes: A Cross-Sectional Study in Men.

BACKGROUND: At a population level, the relation between dairy consumption and gut microbiome composition is poorly understood. OBJECTIVES: We sought to study the cross-sectional associations between individual dairy foods (i.e., milk, yogurt, and cheese), as well as total dairy intake, and the gut microbiome composition in a large, representative sample of men living in south-eastern Australia. METHODS: Data on 474 men (mean ± SD: 64.5 ± 13.5 y old) from the Geelong Osteoporosis Study were used to assess the cross-sectional association between dairy consumption and gut microbiome. Information on dairy intake was self-reported. Men were categorized as consumers and nonconsumers of milk, yogurt, cheese, and high- and low-fat milk. Milk, yogurt, and cheese intakes were summed to calculate the total dairy consumed per day and categorized into either low (<2.5 servings/d) or high (≥2.5 servings/d) total dairy groups. Fecal samples were analyzed using bacterial 16S ribosomal RNA (rRNA) gene sequencing. After assessment of α and ß diversity, differential abundance analysis was performed to identify bacterial taxa associated with each of milk, yogurt, and cheese consumption compared with nonconsumption, low compared with high total dairy, and low- compared with high-fat milk consumption. All analyses were adjusted for potential confounders. RESULTS: α Diversity was not associated with consumption of any of the dairy groups. Differences in ß diversity were observed between milk and yogurt consumption compared with nonconsumption. Taxa belonging to the genera Ruminococcaceae UCG-010 and Bifidobacterium showed negative and weak positive associations with milk consumption, respectively. A taxon from the genus Streptococcus was positively associated with yogurt consumption, whereas a taxon from the genus Eisenbergiella was negatively associated with cheese consumption. No specific taxa were associated with low- compared with high-fat milk nor low compared with high total dairy consumption. CONCLUSIONS: In men, community-level microbiome differences were observed between consumers and nonconsumers of milk and yogurt. Bacterial taxon-level associations were detected with milk, yogurt, and cheese consumption. Total dairy consumption was not associated with any microbiome measures, suggesting that individual dairy foods may have differential roles in shaping the gut microbiome in men.

Human Milk and Infants With Congenital Heart Disease: A Summary of Current Literature Supporting the Provision of Human Milk and Breastfeeding.

BACKGROUND: Human milk is a life-saving medical intervention. Infants with congenital heart disease are at an increased risk for necrotizing enterocolitis, chylothorax, feeding difficulties, and growth failure. In the absence of evidence-based care, their mothers are also at risk for low milk supply and/or poor breastfeeding outcomes. PURPOSE: Summarize the role of human milk and clinical outcomes for infants with congenital heart disease (CHD). Summarize methods of ideal breastfeeding support. METHODS/SEARCH STRATEGY: PubMed, Cochrane Library, and CINAHL were the databases used. The terms used for the search related to CHD and necrotizing enterocolitis were "human milk" and "necrotizing enterocolitis" and "congenital heart disease." This resulted in a total of 17 publications for review. FINDINGS: Infants receiving exclusive human milk diet are at a lower risk for necrotizing enterocolitis and will have improved weight gain. Infants with chylothorax who receive skimmed human milk have higher weight-for-age scores than formula-fed infants. Maternal breastfeeding education correlates with decreased risk of poor breastfeeding outcomes. IMPLICATIONS FOR PRACTICE: Human milk is the ideal source of nutrition for infants with CHD and should be encouraged by the care team. Evidence-based lactation education and care must be provided to mothers and families prenatally and continue throughout the infant's hospitalization. If a mother's goal is to directly breastfeed, this should be facilitated during the infant's hospital stay. IMPLICATIONS FOR RESEARCH: Evaluate the role between human milk and the incidence of necrotizing enterocolitis, feeding difficulties, and clinical outcomes in the population of infants with CHD.

Epigenomic Links Between Social Determinants of Health and Symptoms: A Scoping Review.

Social determinants of health (SDoH) impact health and wellness. The link between SDoH and adverse health outcomes, including symptom occurrence and severity, may be explained by an individual's physiologic response to one or more SDoH. One potential mechanism underlying this physiologic response linking SDoH and symptoms is the dynamic epigenome. The purpose of this scoping review of the literature was to examine differential susceptibility for symptoms by identifying and summarizing research linking SDoH and symptoms through epigenomic mechanisms. PubMed was searched to identify empirical research where at least one SDoH was an independent or dependent variable, at least one symptom was investigated, and the investigation included an epigenomic measure. Of the 484 articles initially retrieved, after thorough vetting, 41 articles met eligibility. The most studied symptom was depressive symptoms followed by anxiety, cognitive function, sleep dysfunction, and pain. The most frequently studied SDoH were: 1) stress, particularly early life stress and acculturative stress; and 2) trauma, predominantly childhood trauma. DNA methylation and telomere length were the most studied epigenomic measures. Four genes (SLC6A4, BDNF, NR3C1, OXTR) had evidence from multiple studies and across methodological approaches linking SDoH to symptoms. This review supports the inclusion of epigenomic approaches to better understand the link between SDoH and symptoms and provides evidence that SDoH impact telomere length and the methylation of genes involved in neurotransmitter signaling, neuronal survival, behavior, inflammation and stress response.

Treatment heterogeneity and overall survival in patients with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma in the United States.

Background: Gastric or gastroesophageal junction (GEJ) adenocarcinoma is the most common form of gastric cancer diagnosed in the United States (US) each year. Diagnosis typically is in later stages of disease when it has advanced. Patients have been treated with a variety of regimens. Methods: The goal of this retrospective study was to understand if treatment patterns were becoming more homogeneous or remaining heterogeneous using the Herfindahl-Hirschman index (HHI) and if treatments were becoming more concordant to treatment guidelines published by the National Comprehensive Cancer Network (NCCN). HHI scores were calculated for each site by 2-year increments. Trend analyses were conducted for HHI scores over time using a linear regression model. Concordance to Category 1 and any category NCCN guidelines was determined based on the date treatment was initiated with the version of the NCCN guidelines at that time. Time trend analyses were conducted using linear regression models. This study utilized data from the Flatiron Advanced Gastric/Esophageal cohort. This study also examined overall survival (OS) rates estimated by the Kaplan-Meier method by line of therapy. Results: There were no statistically significant differences in HHI scores in the first-line setting over time, suggesting heterogeneity has not improved. Concordance to NCCN treatment guidelines for any category significantly increased over time, however Category 1 regimen concordance remained low in the first-line setting. Concordance over time improved in second-line treatment. Median OS from the start of first-line therapy was 13.57 months. There was no relationship between OS time from initiation of first-line therapy and HHI score, concordance with NCCN guidelines, or concordance with NCCN Category 1 guidelines in the first-line setting. Conclusions: Treatment heterogeneity persists in gastric cancer care, though there is a significant association between heterogeneity and concordance with both Category 1 and any category in the NCCN treatment guidelines, and that concordance has increased over time.

Diet quality and a traditional dietary pattern predict lean mass in Australian women: Longitudinal data from the Geelong Osteoporosis Study.

Low muscle mass is associated with reduced independence and increased risk for falls and fractures. Identification of modifiable risk factors for low muscle mass is thus imperative. This study aimed to examine the longitudinal relationship between both diet quality and patterns and lean mass in Australian women. Data from n = 494 participants of the Geelong Osteoporosis Study's 10- and 15-year women's follow-ups were used (conducted in 2004-08 and 2011-14, respectively), and participants were aged 21-89 years. Self-reported lifestyle and demographics were collected, and food frequency questionnaire data informed the dietary exposure variables: the Australian Recommended Food Score (ARFS); the Dietary Inflammatory Index (DII); and a posteriori dietary patterns. The outcome, Skeletal Muscle Index (SMI), was calculated from DXA-derived appendicular lean mass (ALM) relative to height (ALM kg/m2). Analyses employed Generalised Estimating Equations. A higher ARFS score positively predicted SMI over 5-years, and adjustments for age and physical activity did not attenuate this relationship (B:0.044, (95%CI 0.004, 0.084) kg/m2). Following adjustment, both an anti-inflammatory diet (B:-0.034, (95%CI -0.070, -0.002) kg/m2) and a 'traditional' dietary pattern predicted higher SMI (B:0.081, (95%CI 0.004, 0.158) kg/m2). No other associations were observed. Our study reinforces the importance of diet quality for healthy, aging muscle mass. Furthermore, a less inflammatory diet and a diet comprising a wide variety of plant and animal foods may be conducive to maintenance of muscle mass in women. Further studies investigating diet quality's impact on various muscle health measures over longer time periods are warranted.

Ultraprocessed food and chronic noncommunicable diseases: A systematic review and meta-analysis of 43 observational studies.

This systematic review and meta-analysis investigated the association between consumption of ultraprocessed food and noncommunicable disease risk, morbidity and mortality. Forty-three observational studies were included (N = 891,723): 21 cross-sectional, 19 prospective, two case-control and one conducted both a prospective and cross-sectional analysis. Meta-analysis demonstrated consumption of ultraprocessed food was associated with increased risk of overweight (odds ratio: 1.36; 95% confidence interval [CI], 1.23-1.51; P < 0.001), obesity (odds ratio: 1.51; 95% CI, 1.34-1.70; P < 0.001), abdominal obesity (odds ratio: 1.49; 95% CI, 1.34-1.66; P < 0.0001), all-cause mortality (hazard ratio: 1.28; 95% CI, 1.11-1.48; P = 0.001), metabolic syndrome (odds ratio: 1.81; 95% CI, 1.12-2.93; P = 0.015) and depression in adults (hazard ratio: 1.22; 95% CI, 1.16-1.28, P < 0.001) as well as wheezing (odds ratio: 1.40; 95% CI, 1.27-1.55; P < 0.001) but not asthma in adolescents (odds ratio: 1.20; 95% CI, 0.99-1.46; P = 0.065). In addition, consumption of ultraprocessed food was associated with cardiometabolic diseases, frailty, irritable bowel syndrome, functional dyspepsia and cancer (breast and overall) in adults while also being associated with metabolic syndrome in adolescents and dyslipidaemia in children. Although links between ultraprocessed food consumption and some intermediate risk factors in adults were also highlighted, further studies are required to more clearly define associations in children and adolescents. STUDY REGISTRATION: Prospero ID: CRD42020176752.

The Dietary Inflammatory Index and Human Health: An Umbrella Review of Meta-Analyses of Observational Studies.

Numerous observational studies have investigated the role of the Dietary Inflammatory Index (DII®) in chronic disease risk. The aims of this umbrella review and integrated meta-analyses were to systematically synthesize the observational evidence reporting on the associations between the DII and health outcomes based on meta-analyses, and to assess the quality and strength of the evidence for each associated outcome. This umbrella review with integrated meta-analyses investigated the association between the DII and a range of health outcomes based on meta-analyses of observational data. A credibility assessment was conducted for each outcome using the following criteria: statistical heterogeneity, 95% prediction intervals, evidence for small-study effect and/or excess significance bias, as well as effect sizes and P values using calculated random effects meta-analyses. In total, 15 meta-analyses reporting on 38 chronic disease-related outcomes were included, incorporating a total population of 4,360,111 subjects. Outcomes (n = 38) were examined through various study designs including case-control (n = 8), cross-sectional (n = 5), prospective (n = 5), and combination (n = 20) study designs. Adherence to a pro-inflammatory dietary pattern had a significant positive association with 27 (71%) of the included health outcomes (P value < 0.05). Using the credibility assessment, Class I (Convincing) evidence was identified for myocardial infarction only, Class II (Highly suggestive) evidence was identified for increased risk of all-cause mortality, overall risk of incident cancer, and risk of incident site-specific cancers (colorectal, pancreatic, respiratory, and oral cancers) with increasing (more pro-inflammatory) DII score. Most outcomes (n = 31) presented Class III (Suggestive) or lower evidence (Weak or No association). Pro-inflammatory dietary patterns were nominally associated with an increased risk of many chronic disease outcomes. However, the strength of evidence for most outcomes was limited. Further prospective studies are required to improve the precision of the effect size.

The Role of Human Milk in Decreasing Necrotizing Enterocolitis Through Modulation of the Infant Gut Microbiome: A Scoping Review.

BACKGROUND: Necrotizing enterocolitis is associated with a high incidence of morbidity and mortality in premature infants. Human milk minimizes necrotizing enterocolitis risk, although the mechanism of protection is not thoroughly understood. Increasingly, dysbiosis of the infant gut microbiome, which is affected by infant diet, is hypothesized to play a role in necrotizing enterocolitis pathophysiology. RESEARCH AIM: The aim of this scoping review was to summarize the state of the science regarding the hypothesis that the gut microbiome composition is a mediator of the relationship between human milk and decreased incidence of necrotizing enterocolitis within a sample of human infants. METHODS: Electronic databases and reference lists were searched for peer-reviewed primary research articles addressing the link between human milk, gut microbiome composition, and subsequent incidence of necrotizing enterocolitis among human infants. RESULTS: A total of four studies met criteria for inclusion in this review. Of these, evidence supporting the link between human milk, gut microbiome composition, and necrotizing enterocolitis was found in two (50%) studies. CONCLUSION: Some evidence linking all three variables is provided in this review. Given the small number of available studies, and the limitations of those studies, more research is urgently needed to thoroughly understand the protection against necrotizing enterocolitis gained through the provision of human milk.

Obesity, Akkermansia muciniphila, and Proton Pump Inhibitors: Is there a Link?

OBJECTIVE: The gut bacterium Akkermansia muciniphila (A. muciniphila), has been linked to body composition and metabolism. However, the role of lifestyle factors and medication use in these relationships has not been considered. This study aimed to assess the relative abundance of A. muciniphila in participants and investigate its association with obesity, with consideration of potential confounding factors. METHODS: Participants included 158 men of the Geelong Osteoporosis Study with dual-energy X-ray absorptiometry data, 16S rRNA gene bacterial profiling of stool samples, and lifestyle data. The relative abundance of A. muciniphila was estimated from total sequence reads, while obesity status was quantified by fat mass index (FMI, kg/m2). RESULTS: In this cohort (66 ± 12 yr, mean ± SD), the most common medications were proton pump inhibitors (PPIs) (28%), and these were associated with both high FMI and decreased abundance of A. muciniphila. Before and after adjustments for PPIs, participants with substantial A. muciniphila (abundance ≥0.1%, n = 94) compared to very low (abundance <0.1%, n = 64), had lower FMI (adjusted -1.33 (95%CI -2.30, -0.36) kg/m2, p = 0.007). CONCLUSIONS: In this sample, relative abundance of A. muciniphila was inversely associated with high FMI, independent of PPI use. The relationship between obesity, reflux medication, and the gut microbiome warrants further investigation.

Efficacy and safety of fecal microbiota transplantation for the treatment of diseases other than Clostridium difficile infection: a systematic review and meta-analysis.

The intestinal microbiome has been identified as a key modifier for a variety of health conditions. Fecal Microbiota Transplantation (FMT) has emerged as a fast, safe, and effective means by which to modify the intestinal microbiome and potentially treat a variety of health conditions. Despite extensive research of FMT for CDI, there is a lack of clarity informed by systematic synthesis of data regarding the safety and efficacy of FMT for other health conditions. This systematic review used PRISMA guidelines and was prospectively registered with PROSPERO (CRD42018104243). In March 2020, a search of MEDLINE, EMBASE, and PsycINFO was conducted. We identified 26 eligible studies. A meta-analysis of FMT for active Ulcerative Colitis (UC) showed that FMT significantly improved rates of clinical remission (OR = 3.634, 95% CI = 1.940 to 6.808, I2 = 0%, p < .001), clinical response (OR = 2.634, 95% CI = 1.441 to 4.815, I2 = 33%, p = .002) and endoscopic remission (OR = 4.431, 95% CI = 1.901 to 10.324, I2 = 0%, p = .001). With respect to Irritable Bowel Syndrome, a meta-analysis showed no significant change in symptoms following FMT (p = .739). Hepatic disorders, metabolic syndrome, and antibiotic-resistant organisms were conditions with emerging data on FMT. Serious adverse events (AE) were more often reported in control group participants (n = 43) compared with FMT group participants (n = 26). There were similar rates of mild to moderate AE in both groups. Preliminary data suggest that FMT is a potentially safe, well-tolerated and efficacious treatment for certain conditions other than CDI, with evidence for active UC being the most compelling.

An updated understanding of the mechanisms involved in chemotherapy-induced neuropathy.

The burdensome condition of chemotherapy-induced peripheral neuropathy occurs with various chemotherapeutics, including bortezomib, oxaliplatin, paclitaxel and vincristine. The symptoms, which include pain, numbness, tingling and loss of motor function, can result in therapy titrations that compromise therapy efficacy. Understanding the mechanisms of chemotherapy-induced peripheral neuropathy is therefore essential, yet incompletely understood. The literature presented here will address a multitude of molecular and cellular mechanisms, beginning with the most well-understood cellular and molecular-level changes. These modifications include alterations in voltage-gated ion channels, neurochemical transmission, organelle function and intracellular pathways. System-level alterations, including changes to glial cells and cytokine activation are also explored. Finally, we present research on the current understanding of genetic contributions to this condition. Suggestions for future research are provided.

A recreational dose of methylphenidate, but not methamphetamine, decreases anxiety-like behavior in female rats.

Methylphenidate (MPH) and methamphetamine (METH) are two commonly abused psychomotor stimulants that impact anxiety, but in a manner that is currently unclear. This study adds to the literature by testing the effects of MPH and METH on anxiety in adult female rats, which has not previously been studied. In Experiment1, changes in anxiety-like behavior were determined using the Elevated Plus Maze (EPM) following either an acute injection of saline, METH (1 mg/kg), or MPH (10 mg/kg). Changes in general locomotion were measured using the open field test. MPH, but not METH, significantly decreased anxiety; MPH and METH were associated with increased activity in the open field. In Experiment2, we compared the effects of three once daily injections of saline to MPH (10 mg/kg) or METH (1 mg/kg). As with the acute dosing, repeated exposure to MPH, but not METH, decreased anxiety, and both drugs increased locomotion. Neither acute nor chronic dosing produced a change in locomotion during the EPM, indicating that the anxiolytic effects of MPH are independent of changes in locomotor behavior. These findings add further clarification to the literature investigating the psychoactive properties of MPH, with a special and needed emphasis on female behavior.

Mechanisms involved in the development of chemotherapy-induced neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and painful condition seen in patients undergoing treatment with common agents such as vincristine, paclitaxel, oxaliplatin and bortezomib. The mechanisms of this condition are diverse, and include an array of molecular and cellular contributions. Current research implicates genetic predispositions to this condition, which then may influence cellular responses to chemotherapy. Processes found to be influenced during CIPN include increased expression of inflammatory mediators, primarily cytokines, which can create cascading effects in neurons and glia. Changes in ion channels and neurotransmission, as well as changes in intracellular signaling and structures have been implicated in CIPN. This review explores these issues and suggests considerations for future research.

The anterior cingulate cortex and pain processing.

The neural network that contributes to the suffering which accompanies persistent pain states involves a number of brain regions. Of primary interest is the contribution of the cingulate cortex in processing the affective component of pain. The purpose of this review is to summarize recent data obtained using novel behavioral paradigms in animals based on measuring escape and/or avoidance of a noxious stimulus. These paradigms have successfully been used to study the nature of the neuroanatomical and neurochemical contributions of the anterior cingulate cortex (ACC) to higher order pain processing in rodents.

Subclinical peripheral neuropathy in patients with multiple myeloma before chemotherapy is correlated with decreased fingertip innervation density.

PURPOSE: The goal in this study was to determine the incidence of subclinical neuropathy in treatment-naive patients with multiple myeloma (MM) with no history of peripheral neuropathy using quantitative sensory tests (QSTs) and its correlation with innervation density of the extremities using noninvasive laser reflectance confocal microscopy. PATIENTS AND METHODS: QST results were collected for 27 patients with a diagnosis of MM and compared with data collected from 30 age- and sex-matched healthy volunteers. Skin temperature, sensorimotor function (grooved pegboard test), and detection thresholds for temperature, sharpness, and low-threshold mechanical stimuli (von Frey monofilaments and bumps detection test) were measured. Meissner's corpuscle (MC) density in the fingertips was assessed using in vivo laser reflectance confocal microscopy. RESULTS: Patients showed a high incidence (> 80%) of ≥ one subclinical QST deficit. These included increased von Frey, bumps, and warmth detection thresholds as compared with healthy volunteers. Patients also showed increases in cold pain, sensorimotor deficits (grooved pegboard test), and higher overall neuropathy scores. MC density was significantly lower in patients than controls and showed significant inverse correlation with bumps detection threshold. CONCLUSION: Patients with MM commonly present with sensory and sensorimotor deficits before undergoing treatment, and these deficits seem to result from disease-related decreases in peripheral innervation density.