Utilization of the ketogenic diet for adults with status epilepticus.

BACKGROUND: The ketogenic diet (KD) is a high-fat, low-carbohydrate diet with therapeutic potential in refractory seizures, both in outpatient and inpatient settings. Successful implementation of KD involves a multifaceted, interdisciplinary approach to address anticipated challenges. We sought to characterize the utilization of KD among healthcare providers caring for adults with status epilepticus (SE). METHODS: We distributed a web-based survey through professional societies, including the American Academy of Neurology (AAN), Neurocritical Care Society (NCS), American Epilepsy Society (AES), Neuro Anesthesia and Critical Care Society (NACCS), and the Academy of Nutrition and Dietetics (AND), and via research contacts. We asked respondents about practice experience and experience using KD as a treatment for SE. Descriptive statistics and Chi-square tests were used to analyze the results. RESULTS: Of 156 respondents, 80% of physicians and 18% of non-physicians reported experience with KD for SE. Anticipated difficulty in achieving ketosis (36.3%), lack of expertise (24.2%), and lack of resources (20.9%) were identified as the most important barriers limiting the utilization of KD. The absence of dietitians (37.1%) or pharmacists (25.7%) support was the most important missing resource. Reasons for stopping KD included perceived ineffectiveness (29.1%), difficulty achieving ketosis (24.6%), and side effects (17.3%). Academic centers had more experience with the use of KD and greater EEG monitoring availability and fewer barriers to its implementation. The need for randomized clinical trials supporting efficacy (36.5%) and better practice guidelines for implementation and maintenance of KD (29.6%) were cited most frequently as factors to increase utilization of KD. CONCLUSION: This study identifies important barriers to the utilization of KD as a treatment for SE despite evidence supporting its efficacy in the appropriate clinical context, namely lack of resources and interdisciplinary support, and lack of established practice guidelines. Our results highlight the need for future research to improve understanding of the efficacy and safety of KD along with better interdisciplinary collaborations to increase its utilization.

Preterm Birth and Other Measures of Infant Biological Vulnerability: Associations with Maternal Sensitivity and Infant Cognitive Development.

INTRODUCTION: Low birth weight (LBW), biological vulnerability that includes preterm birth (PTB) and small for gestational age (SGA), is associated with reduced maternal sensitivity ("making accurate inferences about an infant's physical and emotional needs and responding appropriately") and impaired infant cognitive development. However, research does not examine if preterm birth, SGA, or both drive these associations. This study separated these measures of biological vulnerability to examine associations of LBW, PTB, and SGA with maternal sensitivity and infant cognitive development (controlling for maternal depression, breastfeeding, and demographic covariates). METHODS: The sample included 6900 9-month-old infants from the Early Childhood Longitudinal Study-Birth Cohort and used birth certificate data, maternal interviews, assessments of maternal sensitivity and infant cognitive development. Multiple linear regressions examined LBW, PTB, and SGA associations with concurrent measures of maternal sensitivity and infant cognition. RESULTS: Of the biological vulnerabilities, preterm birth had the strongest negative association with maternal sensitivity (F1,6450 = 29.48 versus 15.33 and 5.51, ps < .001) and infant cognitive development (F1,6450) = 390.65 versus 248.02 and 14.43, ps < .001). In the final regression model, preterm birth and maternal sensitivity were uniquely associated with infant cognitive development (R2 = .05, p < .001), after controlling for maternal depression, breastfeeding, and demographics. CONCLUSION: In this nationally representative infant sample infants, PTB had a stronger negative association with both maternal sensitivity and infant cognitive development in comparison to SGA or LBW. The LBW designation combines infants born preterm with SGA infants, potentially minimizing differences in developmental outcomes of PTB and SGA infants.

Does breastfeeding account for the association between maternal sensitivity and infant cognitive development in a large, nationally representative cohort?

BACKGROUND: Previous research has established that exposure to high maternal sensitivity is positively associated with advances in infant cognitive development. However, there are many fixed and modifiable factors that influence this association. This study investigates whether the association between maternal sensitivity and infant cognitive development in the first year of life is accounted for by other factors, such as breastfeeding, maternal depressive symptoms, maternal alcohol use, infant birth weight or demographic covariates. METHODS: Using data from the Early Childhood Longitudinal Study-Birth (ECLS-B) Cohort, a nationally representative sample of U.S. born children, multi-variable regression analyses was used to examine whether breastfeeding, maternal depressive symptoms and alcohol use were associated with maternal sensitivity, as measured by the Nursing Child Assessment Teaching Scale (NCATS), and with infant cognitive development, as measured by the Bayley Scales of Infant Development, Short Form, Research Edition, after controlling for demographic covariates (infant sex, maternal age, education, race/ethnicity, income, parity, family structure) and infant birth weight. RESULTS: Breastfeeding, depressive symptoms and alcohol use were not associated with maternal sensitivity scores after controlling for demographic covariates and infant birth weight. However, breastfeeding (ß = .079, p < .001), depressive symptoms (ß = -.035, p < .05), and maternal sensitivity (ß = .175, p < .001) were each significantly associated with infant cognitive development scores, even after controlling for demographic covariates and birthweight (R2 = .053, p < .001). The association between maternal sensitivity and infant cognitive development did not attenuate after adjusting for breastfeeding. Instead, both sensitivity and breastfeeding independently contributed to higher infant cognitive development scores. CONCLUSION: Maternal sensitivity and breastfeeding are separate means to advancing infant cognitive development. This study is significant because it is the first to examine breastfeeding, maternal depressive symptoms and alcohol use together, upon the association between maternal sensitivity and infant cognitive development, after adjusting for demographic covariates and infant birthweight. Maternal sensitivity, a measurable quality, advances infants' cognitive development. Moreover, sensitivity and breastfeeding had independent effects upon cognitive development after controlling for multiple fixed and modifiable covariates. Understanding factors impacting the association between sensitivity and infant cognitive development provide avenues for developing more effective parenting interventions.

Neutrophil-mediated fibroblast-tumor cell il-6/stat-3 signaling underlies the association between neutrophil-to-lymphocyte ratio dynamics and chemotherapy response in localized pancreatic cancer: A hybrid clinical-preclinical study.

Background: Partial/complete pathologic response following neoadjuvant chemotherapy (NAC) in pancreatic cancer (PDAC) patients undergoing pancreatectomy is associated with improved survival. We sought to determine whether neutrophil-to-lymphocyte ratio (NLR) dynamics predict pathologic response following chemotherapy in PDAC, and if manipulating NLR impacts chemosensitivity in preclinical models and uncovers potential mechanistic underpinnings underlying these effects. Methods: Pathologic response in PDAC patients (n=94) undergoing NAC and pancreatectomy (7/2015-12/2019) was dichotomized as partial/complete or poor/absent. Bootstrap-validated multivariable models assessed associations between pre-chemotherapy NLR (%neutrophils÷%lymphocytes) or NLR dynamics during chemotherapy (ΔNLR = pre-surgery-pre-chemotherapy NLR) and pathologic response, disease-free survival (DFS), and overall survival (OS). To preclinically model effects of NLR attenuation on chemosensitivity, Ptf1aCre/+; KrasLSL-G12D/+;Tgfbr2flox/flox (PKT) mice and C57BL/6 mice orthotopically injected with KrasLSL-G12D/+;Trp53LSL-R172H/+;Pdx1Cre(KPC) cells were randomized to vehicle, gemcitabine/paclitaxel alone, and NLR-attenuating anti-Ly6G with/without gemcitabine/paclitaxel treatment. Results: In 94 PDAC patients undergoing NAC (median:4 months), pre-chemotherapy NLR (p<0.001) and ΔNLR attenuation during NAC (p=0.002) were independently associated with partial/complete pathologic response. An NLR score = pre-chemotherapy NLR+ΔNLR correlated with DFS (p=0.006) and OS (p=0.002). Upon preclinical modeling, combining NLR-attenuating anti-Ly6G treatment with gemcitabine/paclitaxel-compared with gemcitabine/paclitaxel or anti-Ly6G alone-not only significantly reduced tumor burden and metastatic outgrowth, but also augmented tumor-infiltrating CD107a+-degranulating CD8+ T-cells (p<0.01) while dampening inflammatory cancer-associated fibroblast (CAF) polarization (p=0.006) and chemoresistant IL-6/STAT-3 signaling in vivo. Neutrophil-derived IL-1ß emerged as a novel mediator of stromal inflammation, inducing inflammatory CAF polarization and CAF-tumor cell IL-6/STAT-3 signaling in ex vivo co-cultures. Conclusions: Therapeutic strategies to mitigate neutrophil-CAF-tumor cell IL-1ß/IL-6/STAT-3 signaling during NAC may improve pathologic responses and/or survival in PDAC. Funding: Supported by KL2 career development grant by Miami CTSI under NIH Award UL1TR002736, Stanley Glaser Foundation, American College of Surgeons Franklin Martin Career Development Award, and Association for Academic Surgery Joel J. Roslyn Faculty Award (to J. Datta); NIH R01 CA161976 (to N.B. Merchant); and NCI/NIH Award P30CA240139 (to J. Datta and N.B. Merchant).

Predictors of co-parenting in Mexican American families and direct effects on parenting and child social emotional development.

The present study examined associations between parents' levels of acculturation depressive symptoms, family support, and couple relationship quality with coparenting conflict. We also explored the effects of coparenting conflict on parenting and infant social development in a sample of low-income Mexican American (n=735) infants (age 9 months) and their parents. Results indicated that couple conflict was the strongest predictor of coparenting conflict. Coparenting conflict had a significant effect on mother-infant interaction and father engagement. The effects of coparenting on father caregiving varied by father's level of acculturation; when there is high coparenting conflict, more acculturated fathers engaged in more caregiving than less acculturated fathers. Coparenting conflict was not predictive of infant social development.

Predictors of coparenting in Mexican American families and links to parenting and child social emotional development.

The present study examined associations between parents' levels of acculturation depressive symptoms, family support, and couple relationship quality with coparenting conflict. We also explored the effects of coparenting conflict on parenting and infant social development in a sample of low-income Mexican American (n = 735) infants (age 9 months) and their parents. Results indicated that couple conflict was the strongest predictor of coparenting conflict. Coparenting conflict had a significant effect on mother--infant interaction and father engagement. The effects of coparenting on father caregiving varied by father's level of acculturation; when there is high coparenting conflict, more acculturated fathers engaged in more caregiving than do less acculturated fathers. Coparenting conflict was not predictive of infant social development.

Low-income, nonresident father involvement with their toddlers: variation by fathers' race and ethnicity.

Using data from a racially and ethnically diverse sample of low-income mothers of 2-year-old children participating in the Early Head Start Research and Evaluation Project (N = 883), the authors examined fathers' education and employment, mother-father relationship, and mothers' relationships with kin in the household to explain variation in nonresident father involvement across racial and ethnic groups. Nonresident White fathers were less involved with their children than were African American and Latino fathers. This difference was explained by the status of mother-father relationships. White nonresident fathers were less likely than minority nonresident fathers to maintain romantic relationships with their child's mother. Mothers in the White father group were also more likely to re-partner, which negatively related to biological fathers' involvement. These findings suggest that approaches to strengthen nonresident father involvement in children's lives need to consider how father ethnicity and mother-father relations are associated with differential patterns of father involvement.

Father Involvement in Infancy: Influences of Past and Current Relationships.

Men's childhood experiences with their parents, their current relationship with their partners, and demographic factors were examined in relation to father-infant interactions. Participants were 60 racially and ethnically diverse, inner-city men and their 6- to 11-month-old infants. Father-infant interactions were videotaped during semistructured free play in participants' homes. The quality of men's interactions with their infants was assessed using Likert ratings of their responsive-didactic and negative-overbearing behaviors. Men engaged in significantly more responsive-didactic behaviors than negative-overbearing behaviors. A cumulative score of protective demographic factors (i.e., men residing with their infants, being married, completing high school, and obtaining income above the sample's median level) and men's experiences of childhood acceptance from their fathers uniquely predicted their responsive-didactic behaviors. Men's relationships with their partners were homogeneously strong and unrelated to fathering behaviors. This study builds on extant literature by providing a broader conceptualization of father-infant relationships and applying observational methods to the study of fathering in minority, low-income men.

Mexican American Mothers and Fathers' Prenatal Attitudes and Father Prenatal Involvement: Links to Mother-Infant Interaction and Father Engagement.

The present study examines the associations between Mexican American mothers' and fathers' pregnancy intentions, fathers' participation in prenatal activities and mother-infant interactions and father engagement with 9 month-old infants in a nationally representative sample of 735 infants and their parents participating in the Early Childhood Longitudinal Study - Birth Cohort. After controlling for a host of variables, multiple regressions revealed that when mothers wanted the pregnancy, fathers engaged in more literacy and caregiving activities than when mothers did not want the pregnancy. When couples disagreed about wanting the pregnancy, fathers engaged in more literacy activities and showed more warmth than when they agreed. Relationship quality significantly moderated the effects of parents' wantedness on mother-infant interactions and fathers' engagement in literacy activities.

Who Stays and Who Leaves? Father Accessibility Across Children's First 5 Years.

OBJECTIVE: This longitudinal investigation examines whether fathers' prenatal involvement (e.g., attending doctor appointments and discussing pregnancy with mother) and residence status at infant's birth predict the first time a father becomes inaccessible to his child (defined as seeing child fewer than a few times per month) at six developmental time points in children's first 5 years. DESIGN: Data were gathered from 2,160 ethnically diverse mothers (i.e., European American, African American, and Latin American) who participated in the National Early Head Start Research and Evaluation Project. Survival analysis was used to predict the timing of father inaccessibility based on interviews. RESULTS: By prekindergarten, fathers' residence at birth and prenatal involvement decreased their risk of being inaccessible to their children for the first time by 71% and 47%, respectively, after adjusting for all other variables in the model. Residence at birth was a stronger predictor of the timing of father inaccessibility than was prenatal involvement for European American and Latin American fathers; for African American fathers, prenatal involvement was a stronger predictor of the timing of father inaccessibility than nonresidential status at birth. Nearly 65% of fathers who were engaged in both prenatal activities remained consistently accessible to their child through child age of 63 months, whereas nearly 50% of fathers who were not prenatally involved were already inaccessible by the time infants were 3 months. CONCLUSION: These findings have implications for early intervention programs aimed at strengthening the role of fathers in their families from the prenatal period.

Parental interactions with Latino infants: variation by country of origin and English proficiency.

This study examined variation in mother-infant interactions, father engagement, and infant cognition as a function of country of origin, socioeconomic status, and English language proficiency in a national sample of Latino infants (age 9 months) born in the United States and living with both biological parents (N=1,099). Differences between Mexican-American infants, who had lower mother-infant interaction scores and less father physical play than did the other Latino infants, were associated with differences in acculturation (both parents' English proficiency). Indicators of acculturation and paternal reports of happiness with partner were associated with paternal engagement. Indicators of acculturation were also related to mother-infant interactions. Infant cognitive scores were associated with maternal interaction but not father engagement, and maternal but not paternal mental health.

Fathers and mothers at play with their 2- and 3-year-olds: contributions to language and cognitive development.

Father-child and mother-child engagements were examined longitudinally in relation to children's language and cognitive development at 24 and 36 months. The study involved a racially/ethnically diverse sample of low-income, resident fathers (and their partners) from the National Early Head Start evaluation study (n=290). Father-child and mother-child engagements were videotaped for 10 min at home during semistructured free play, and children's language and cognitive status were assessed at both ages. Fathers' and mothers' supportive parenting independently predicted children's outcomes after covarying significant demographic factors. Moreover, fathers' education and income were uniquely associated with child measures, and fathers' education consistently predicted the quality of mother-child engagements. Findings suggest direct and indirect effects of fathering on child development.