Biomarkers for predicting disease course in Sanfilippo syndrome: An urgent unmet need in childhood-onset dementia.

Sanfilippo syndrome (MPS III) is an autosomal recessive inherited disorder causing dementia in children, following an essentially normal early developmental period. First symptoms typically include delayed language development, hyperactivity and/or insomnia from 2 years of age, followed by unremitting and overt loss of previously acquired skills. There are no approved treatments, and the median age of death is 18 years. Treatments under clinical trial demonstrate therapeutic benefit when applied pre-symptomatically in children diagnosed early through known familial inheritance risk. Newborn screening for Sanfilippo syndrome would enable pre-symptomatic diagnosis and optimal therapeutic benefit, however, many fold more patients with Sanfilippo syndrome are expected to be identified in the population than present with childhood dementia. Therefore, the capacity to stratify which Sanfilippo infants will need treatment in toddlerhood is necessary. While diagnostic methods have been developed, and continue to be refined, currently there are no tools or laboratory-based biomarkers available to provide pre-symptomatic prognosis. There is also a lack of progression and neurocognitive response-to-treatment biomarkers; disease stage and rate of progression are currently determined by age at symptom onset, loss of cerebral grey matter volume by magnetic resonance imaging and developmental quotient score for age. Robust blood-based biomarkers are an urgent unmet need. In this review, we discuss the development of biomarker assays for Sanfilippo based on the neuropathological pathways known to change leading into symptom onset and progression, and their performance as biomarkers in other neurodegenerative diseases. We propose that neural-derived exosomes extracted from blood may provide an ideal liquid biopsy to detect reductions in synaptic protein availability, and mitochondrial function. Furthermore, given the prominent role of neuroinflammation in symptom expression, glial fibrillary acidic protein detection in plasma/serum, alongside measurement of active brain atrophy by neurofilament light chain, warrant increased investigation for prognostic, progression and neurocognitive response-to-treatment biomarker potential in Sanfilippo syndrome and potentially other childhood dementias.

Urinary neopterin: A novel biomarker of disease progression in amyotrophic lateral sclerosis.

BACKGROUND AND PURPOSE: The aim was to evaluate urinary neopterin, a marker of pro-inflammatory state, as a potential biomarker of disease prognosis and progression in amyotrophic lateral sclerosis (ALS); and to compare its utility to urinary neurotrophin receptor p75 extracellular domain (p75ECD ). METHODS: This was an observational study including 21 healthy controls and 46 people with ALS, 29 of whom were sampled longitudinally. Neopterin and p75ECD were measured using enzyme-linked immunoassays. Baseline and longitudinal changes in clinical measures, neopterin and urinary p75ECD were examined, and prognostic utility was explored by survival analysis. RESULTS: At baseline, urinary neopterin was higher in ALS compared to controls (181.7 ± 78.9 µmol/mol creatinine vs. 120.4 ± 60.8 µmol/mol creatinine, p = 0.002, Welch's t test) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Combining previously published urinary p75ECD results from 22 ALS patients with a further 24 ALS patients, baseline urinary p75ECD was also higher compared to healthy controls (6.0 ± 2.7 vs. 3.2 ± 1.0 ng/mg creatinine, p < 0.0001) and correlated with the Revised ALS Functional Rating Scale (r = -0.36, p = 0.01). Urinary neopterin and p75ECD correlated with each other at baseline (r = 0.38, p = 0.009). In longitudinal analysis, urinary neopterin increased on average (±SE) by 6.8 ± 1.1 µmol/mol creatinine per month (p < 0.0001) and p75ECD by 0.19 ± 0.02 ng/mg creatinine per month (p < 0.0001) from diagnosis in 29 ALS patients. CONCLUSION: Urinary neopterin holds promise as marker of disease progression in ALS and is worthy of future evaluation for its potential to predict response to anti-inflammatory therapies.

Family Functioning Profiles in Emerging Adults: Associations with Personal and Parental Psychological Problems.

Although recent research has examined family profiles in younger children, emerging adults have not been examined as extensively despite evidence that families continue to be important to emerging adults. The current study examined family functioning profiles and associated psychological problems of both offspring and parents from the perspective of 585 college-attending emerging adults. Results supported six profiles where lower functioning groups generally had more psychological problems relative to higher functioning groups and with specific maternal and paternal differences. The current study advances family functioning research by demonstrating that family profiles can be identified and associated with psychological problems for both parents and emerging adults.

Patterns of Genetic Coding Variation in a Native American Population before and after European Contact.

The effects of European colonization on the genomes of Native Americans may have produced excesses of potentially deleterious features, mainly due to the severe reductions in population size and corresponding losses of genetic diversity. This assumption, however, neither considers actual genomic patterns that existed before colonization nor does it adequately capture the effects of admixture. In this study, we analyze the whole-exome sequences of modern and ancient individuals from a Northwest Coast First Nation, with a demographic history similar to other indigenous populations from the Americas. We show that in approximately ten generations from initial European contact, the modern individuals exhibit reduced levels of novel and low-frequency variants, a lower proportion of potentially deleterious alleles, and decreased heterozygosity when compared to their ancestors. This pattern can be explained by a dramatic population decline, resulting in the loss of potentially damaging low-frequency variants, and subsequent admixture. We also find evidence that the indigenous population was on a steady decline in effective population size for several thousand years before contact, which emphasizes regional demography over the common conception of a uniform expansion after entry into the Americas. This study examines the genomic consequences of colonialism on an indigenous group and describes the continuing role of gene flow among modern populations.

The adaptation and feasibility of dialectical behaviour therapy for adults with intellectual developmental disabilities and transdiagnoses: A pilot community-based randomized controlled trial.

INTRODUCTION: Preliminary evidence suggests dialectical behaviour therapy (DBT) may be beneficial for persons with intellectual disabilities. This pilot randomized controlled trial aimed to determine the feasibility of adapted DBT for adults with intellectual disabilities and co-morbid psychiatric disorders in the community. METHODS: An adapted DBT programme (aDBT-ID) was delivered to adults with mild-to-moderate intellectual disability (n = 20) and their caregivers (n = 20). A single-blind, mixed-methods design was employed with treatment (n = 10) and control (n = 10). In addition to feasibility, pre-post-measures of emotional regulation, anger and mental health were taken from clients and caregivers. RESULTS: Results suggest it was feasible and beneficial to deliver adapted DBT in the community. Qualitative findings found both participants and caregivers were satisfied with the treatment delivery. No differences between conditions were found. CONCLUSION: This pilot study highlights the feasibility of adapted DBT for individuals with intellectual disabilities and the practicalities of delivering community-based inclusive research.

Congenital infections as contributors to the onset of diabetes in children: A longitudinal study in the United States, 2001-2017.

BACKGROUND: Maternal infections during pregnancy, particularly with rubella virus, were reported to increase the risk of diabetes in children. Widespread vaccination has decreased the number of infants with congenital rubella syndrome in the United States, although it remains a problem in developing countries. Because vaccine hesitancy has recently increased, we investigated the association between congenital infections with subsequent diabetes risk in children in the United States. METHODS: Using data from a nationwide private health insurer for years 2001-2017, 1 475 587 infants were followed for an average of 3.9 years (maximum 16.5 years). Information was obtained regarding congenital infections (rubella, cytomegalovirus, other congenital infections) and perinatal infections, as well as for the development of diabetes mellitus and diabetic ketoacidosis. RESULTS: There were 781 infants with congenital infections and 73 974 with perinatal infections. Diabetes developed in 3334 children. The odds of developing diabetes for infants with congenital rubella infection were 12-fold greater (P = .013) and, for infants with congenital cytomegalovirus infection, were 4-fold greater (P = .011) than infants without congenital or perinatal infection. Infants with other congenital infections had 3-fold greater odds of developing diabetes (P = .044). Results were similar for diabetes ketoacidosis. Infants with other perinatal infections had 49% greater odds of developing diabetes during the follow-up period (P < .001). CONCLUSION: Congenital and other perinatal infections are associated with elevated risks of developing diabetes mellitus during childhood. Vaccination for rubella remains an important preventive action to reduce the incidence of diabetes in children.

Declining ages at menarche in an agrarian rural region of Poland.

OBJECTIVE: Age at menarche in Poland has varied with political and socioeconomic changes. An increase in age at menarche corresponded to a period of economic crisis and food rationing between 1976 and 1989. Experiencing food shortages in utero or during childhood development can affect menarcheal timing, but this national effect may be buffered in local agrarian regions growing their own food. Here we examine patterns of age at menarche over time in the rural, agrarian Beskid Wyspowy region of southern Poland. METHODS: This study examined menarcheal timing using data collected from Polish women (n = 1326) recruited at the Mogielica Human Ecology Study Site between 2003 and 2018. Simple linear regressions were used to assess changing ages at menarche over time. Comparisons between ages at menarche for women born before and after the fall of communism in 1989 were assessed via one-way analysis of variance. RESULTS: Age at menarche has declined over time in the Beskid Wyspowy region of southern Poland from 1920 to 2000 (R2 = .08, P < .0001). There was not a statistically significant increase or decrease in age at menarche for women born and growing up during the period of food rationing. CONCLUSIONS: The declining age at menarche is likely reflective of a transitioning environment, suggesting that major socioeconomic changes affect life history traits like pubertal timing. Living in agricultural regions may have helped buffer the increasing ages at menarche seen in other areas of Poland during times of food rationing.

From maternal tending to adolescent befriending: The adolescent transition of social support.

Attachment theory holds that parental relationships have lifelong effects on offspring social lives. The tend-and-befriend hypothesis posits that female friendships among humans evolved as part of a primate-wide coping mechanism to mediate stress by relying on social support. Here we bridge developmental and evolutionary frameworks to examine adolescent girls' perception of their reliance on female friendship for social support, how perceptions of parental relationships affect peer relationships, and the extent to which parent and peer relationships buffer depressive symptoms. We predict perceived maternal relationship quality will be positively associated with close female friendships, and maternal relationships, paternal relationships, and female friendship will buffer depressive symptoms. Participants were adolescent girls from a summer science camp (N = 95). Participants filled out demographic information, social network surveys, the Parent-Adolescent Communication Scale, and the Center for Epidemiology Depression Scale. Data was analyzed with Pearson's correlations, t tests, and path analysis. Adolescent girls with few female friends, compared with girls who had more than two very close female friends, experienced more depressive symptoms (t = 3.382, p = .001, D = 0.784). Adolescent girls with few female friends experienced more depressive symptoms compared to girls with two or more very close female friends (t = 3.382, p = .001, D = 0.784). Stronger maternal and paternal relationships were associated with having more female friends (maternal: t = -3.213, p = .003, D = 0.837; paternal: t = -2.432; p = .017). In the path analysis model, only maternal relationship quality significantly predicted female friendship category (ß = .33, CR = 2.770, p < .006). Furthermore, participants with two or more very close female friends and higher paternal relationship quality had significantly fewer depressive symptoms (friends; ß = -.19, CR = -2.112, p = .035; paternal: ß = -.33, CR = -3.220, p < .001), and older participants had more depressive symptoms (ß = .17, CR = -1.931, p = .036). These results provide additional support for the tend-and-befriend hypothesis, suggesting that maternal tending sets the stage for close female friendships.

Use of Peripherally Inserted Central Catheters in Patients With Advanced Chronic Kidney Disease: A Prospective Cohort Study.

Background: Existing guidelines, including Choosing Wisely recommendations, endorse avoiding placement of peripherally inserted central catheters (PICCs) in patients with chronic kidney disease (CKD). Objective: To describe the frequency of and characteristics associated with PICC use in hospitalized patients with stage 3b or greater CKD (glomerular filtration rate [GFR] <45 mL/min/1.73 m2). Design: Prospective cohort study. Setting: 52 hospitals participating in the Michigan Hospital Medicine Safety Consortium. Participants: Hospitalized medical patients who received a PICC between November 2013 and September 2016. Measurements: Percentage of patients receiving PICCs who had CKD, frequency of PICC-related complications, and variation in the proportion of PICCs placed in patients with CKD. Results: Of 20 545 patients who had PICCs placed, 4743 (23.1% [95% CI, 20.9% to 25.3%]) had an estimated GFR (eGFR) less than 45 mL/min/1.73 m2 and 699 (3.4%) were receiving hemodialysis. In the intensive care unit (ICU), 30.9% (CI, 29.7% to 32.2%) of patients receiving PICCs had an eGFR less than 45 mL/min/1.73 m2; the corresponding percentage in wards was 19.3% (CI, 18.8% to 19.9%). Among patients with an eGFR less than 45 mL/min/1.73 m2, multilumen PICCs were placed more frequently than single-lumen PICCs. In wards, PICC-related complications occurred in 15.3% of patients with an eGFR less than 45 mL/min/1.73 m2 and in 15.2% of those with an eGFR of 45 mL/min/1.73 m2 or higher. The corresponding percentages in ICU settings were 22.4% and 23.9%. In patients with an eGFR less than 45 mL/min/1.73 m2, PICC placement varied widely across hospitals (interquartile range, 23.7% to 37.8% in ICUs and 12.8% to 23.7% in wards). Limitation: Nephrologist approval for placement could not be determined, and 2.7% of eGFR values were unknown and excluded. Conclusion: In this sample of hospitalized patients who received PICCs, placement in those with CKD was common and not concordant with clinical guidelines. Primary Funding Source: Blue Cross Blue Shield of Michigan and Blue Care Network.

Excess Antibiotic Treatment Duration and Adverse Events in Patients Hospitalized With Pneumonia: A Multihospital Cohort Study.

Background: Randomized trials demonstrate no benefit from antibiotic treatment exceeding the shortest effective duration. Objective: To examine predictors and outcomes associated with excess duration of antibiotic treatment. Design: Retrospective cohort study. Setting: 43 hospitals in the Michigan Hospital Medicine Safety Consortium. Patients: 6481 general care medical patients with pneumonia. Measurements: The primary outcome was the rate of excess antibiotic treatment duration (excess days per 30-day period). Excess days were calculated by subtracting each patient's shortest effective (expected) treatment duration (based on time to clinical stability, pathogen, and pneumonia classification [community-acquired vs. health care-associated]) from the actual duration. Negative binomial generalized estimating equations (GEEs) were used to calculate rate ratios to assess predictors of 30-day rates of excess duration. Patient outcomes, assessed at 30 days via the medical record and telephone calls, were evaluated using logit GEEs that adjusted for patient characteristics and probability of treatment. Results: Two thirds (67.8% [4391 of 6481]) of patients received excess antibiotic therapy. Antibiotics prescribed at discharge accounted for 93.2% of excess duration. Patients who had respiratory cultures or nonculture diagnostic testing, had a longer stay, received a high-risk antibiotic in the prior 90 days, had community-acquired pneumonia, or did not have a total antibiotic treatment duration documented at discharge were more likely to receive excess treatment. Excess treatment was not associated with lower rates of any adverse outcomes, including death, readmission, emergency department visit, or Clostridioides difficile infection. Each excess day of treatment was associated with a 5% increase in the odds of antibiotic-associated adverse events reported by patients after discharge. Limitation: Retrospective design; not all patients could be contacted to report 30-day outcomes. Conclusion: Patients hospitalized with pneumonia often receive excess antibiotic therapy. Excess antibiotic treatment was associated with patient-reported adverse events. Future interventions should focus on whether reducing excess treatment and improving documentation at discharge improves outcomes. Primary Funding Source: Blue Cross Blue Shield of Michigan (BCBSM) and Blue Care Network as part of the BCBSM Value Partnerships program.

Geospatial Variation in Rotavirus Vaccination in Infants, United States, 2010-2017.

We evaluated rotavirus vaccination rates in the United States by using records from a nationwide health database. From data on 519,697 infants, we found 68.6% received the entire rotavirus vaccine series. We noted pockets of undervaccination in many states, particularly in the Northeast and in some western states.

A Program to Prevent Catheter-Associated Urinary Tract Infection in Acute Care.

BACKGROUND: Catheter-associated urinary tract infection (UTI) is a common device-associated infection in hospitals. Both technical factors--appropriate catheter use, aseptic insertion, and proper maintenance--and socioadaptive factors, such as cultural and behavioral changes in hospital units, are important in preventing catheter-associated UTI. METHODS: The national Comprehensive Unit-based Safety Program, funded by the Agency for Healthcare Research and Quality, aimed to reduce catheter-associated UTI in intensive care units (ICUs) and non-ICUs. The main program features were dissemination of information to sponsor organizations and hospitals, data collection, and guidance on key technical and socioadaptive factors in the prevention of catheter-associated UTI. Data on catheter use and catheter-associated UTI rates were collected during three phases: baseline (3 months), implementation (2 months), and sustainability (12 months). Multilevel negative binomial models were used to assess changes in catheter use and catheter-associated UTI rates. RESULTS: Data were obtained from 926 units (59.7% were non-ICUs, and 40.3% were ICUs) in 603 hospitals in 32 states, the District of Columbia, and Puerto Rico. The unadjusted catheter-associated UTI rate decreased overall from 2.82 to 2.19 infections per 1000 catheter-days. In an adjusted analysis, catheter-associated UTI rates decreased from 2.40 to 2.05 infections per 1000 catheter-days (incidence rate ratio, 0.86; 95% confidence interval [CI], 0.76 to 0.96; P=0.009). Among non-ICUs, catheter use decreased from 20.1% to 18.8% (incidence rate ratio, 0.93; 95% CI, 0.90 to 0.96; P<0.001) and catheter-associated UTI rates decreased from 2.28 to 1.54 infections per 1000 catheter-days (incidence rate ratio, 0.68; 95% CI, 0.56 to 0.82; P<0.001). Catheter use and catheter-associated UTI rates were largely unchanged in ICUs. Tests for heterogeneity (ICU vs. non-ICU) were significant for catheter use (P=0.004) and catheter-associated UTI rates (P=0.001). CONCLUSIONS: A national prevention program appears to reduce catheter use and catheter-associated UTI rates in non-ICUs. (Funded by the Agency for Healthcare Research and Quality.).

Private Insurance Coverage for Diabetes Before and After Enactment of the Preexisting Condition Mandate of the Affordable Care Act, 2005-2016.

OBJECTIVES: To examine private insurance coverage for persons with diabetes before and after enactment of the preexisting condition mandate of the Affordable Care Act (ACA) in the United States. METHODS: We conducted a nationwide study in adults aged 20 to 59 years with private health insurance with the Clinformatics Data Mart Database (2005-2016). We used fixed-effects negative binomial regression to evaluate differences in pre-post mandate trends. RESULTS: There was a 4% decline in prevalence rates of type 1 diabetes in adults with private health insurance before the mandate and an 11% increase afterward (P < .001). Coverage increased to the greatest extent (-6% before, +20% after) in those aged 50 to 59 years (P < .001). For type 2 diabetes, there was a significant decline in prevalence before the mandate, which increased afterward in those aged 40 to 49 years (-4% before, 3% after; P = .031) and 50 to 59 years (-6% before, 15% after; P < .001). CONCLUSIONS: Adults with diabetes may have benefited in obtaining private health insurance after implementation of the preexisting condition mandate of the ACA. Public Health Implications. Efforts to limit enforcement of these protections are likely to contribute to setbacks in access to care.

Physical activity in women of reproductive age in a transitioning rural Polish population.

OBJECTIVE: Health research often focuses on moderate and vigorous intensity physical activity while neglecting low-intensity habitual activities. Our aim was to understand habitual physical activity in women from a transitioning economy using a physical activity monitor. METHODS: This study investigated physical activity in 68 healthy premenopausal women (age 18-46) in rural Poland using FitBit One activity trackers for 1 week. Standard anthropometric techniques were used to measure height, weight, and body fat. Daily physical activity data were analyzed for step counts as well as duration and intensity. RESULTS: This sample of rural Polish women traveled a mean of 8428 (SD = 2650) steps per day. Time spent lightly active, fairly active, and very active were measured as 337.1 (SD = 87.8), 19.6 (SD = 30.5), and 6.7 (SD = 8.6) minutes per day, respectively. Total time active and time spent lightly active were associated with daily steps (P < 0.001 for both), and time lightly active increased with age (P = 0.02). No other significant relationships were observed between physical activity measures and BMI, age, or body fat. CONCLUSIONS: In this sample, women spend a significant amount of time engaged in light-intensity physical activity and travel a relatively high number of steps per day. Our data suggest that in this population, total daily activity does not depend on age in women between 18 and 46. We suggest that measurement methods which include low-intensity activity may better characterize habitual physical activity in women who are expected to be performing large amounts of domestic labor.

Duration of Insulin Supply in Type 1 Diabetes: Are 90 Days Better or Worse Than 30 Days?

OBJECTIVE: There have been few studies regarding the duration of insulin prescriptions and patient outcomes. This study evaluated whether A1C varied with the duration of insulin prescription in patients with type 1 diabetes. METHODS: We conducted a longitudinal investigation (from 2001 to 2015) within a nationwide private health insurer. A cohort study was first used to compare A1C after 30-day only, 90-day only, and a combination (30-day and 90-day) of insulin prescriptions. Second, a self-controlled case series was used to compare A1C levels after 30-day versus 90-day prescriptions for the same person. RESULTS: In the cohort study, there were 16,725 eligible patients. Mean A1C was 8.33% for patients with 30-day prescriptions compared to 7.69% for those with 90-day prescriptions and 8.05% for those who had a combination of 30- and 90-day prescriptions (P <0.001). Results were similar when stratified by age and sex. Mean A1C was 7.58% when all prescriptions were mailed versus 8.21% when they were not. In the self-controlled case series, there were 1,712 patients who switched between 30- and 90-day prescriptions. Mean A1C was 7.87% after 30-day prescriptions and 7.69% after 90-day prescriptions (P <0.001). Results were similar when stratified by sex. For this within-person comparison, the results remained significant for those ≥20 years of age (n = 1,536, P <0.001), but not for youth (n = 176, P = 0.972). CONCLUSION: There was a statistically significant but clinically modest decrease in A1C with 90-day versus 30-day insulin prescriptions in adults. A mailed 90-day insulin prescription may be a reasonable choice for adults with type 1 diabetes.

The fear of needles: A systematic review and meta-analysis.

AIMS: The aim of this study was to evaluate the prevalence of needle fear and summarize the characteristics of individuals who exhibit this fear. BACKGROUND: Injections are among the most common medical procedures, yet fear of needles can result in avoidance of preventive measures and treatment. DESIGN: Systematic review and meta-analysis. DATA SOURCES: MEDLINE (1966-2017), Embase (1947-2017), PsycINFO (1967-2017), and CINAHL (1961-2017) were searched, with no restrictions by age, gender, race, language, or country. REVIEW METHODS: The prevalence of needle fear was calculated and restricted maximum likelihood random effects models were used for meta-analysis and meta-regression. RESULTS: The search yielded 119 original research articles which are included in this review, of which 35 contained sufficient information for meta-analysis. The majority of children exhibited needle fear, while prevalence estimates for needle fear ranged from 20-50% in adolescents and 20-30% in young adults. In general, needle fear decreased with increasing age. Both needle fear and needle phobia were more prevalent in females than males. Avoidance of influenza vaccination because of needle fear occurred in 16% of adult patients, 27% of hospital employees, 18% of workers at long-term care facilities, and 8% of healthcare workers at hospitals. Needle fear was common when undergoing venipuncture, blood donation, and in those with chronic conditions requiring injection. CONCLUSIONS: Fear of needles is common in patients requiring preventive care and in those undergoing treatment. Greater attention should be directed to interventions which alleviate fear in high-risk groups.

Using Six Sigma to Reduce the Utilization of Continuous Observations (1: 1) for Safety Precautions.

The need for continuous observation (1:1) of patients for safety precautions, including fall risk, elopement risk, confusion, and aggressive behavior, is highly variable, and it is therefore difficult to plan accurate staffing levels. The high variability in determining when 1:1 staffing for safety is indicated, and for how long, leads to resource strain and high cost to the hospital. A multidisciplinary team analyzed current processes for assigning, monitoring, and discontinuing safety 1:1 care for nonsuicidal patients using Six Sigma methodologies. The team implemented a standardized weaning process to reduce the duration of time on continuous observation and a standardized 4-hour reassessment using a behavior observation-tracking tool to validate the continued need for 1:1 coverage. The interventions resulted in reducing average monthly safety 1:1 staffing hours by 25.6% and saving an estimated $142 000 annually across 6 units. Phase 2 of the project integrated the observation-tracking tool and reassessment check-in into the hospital's electronic medical record for improved tracking and documentation.

Emerging Adult Risky Sexual Behavior Predicted by Parental Overprotection: Moderated Mediation Analysis.

Parental control behaviors are suggested to be related to emerging adult outcomes, such as risky sexual behavior. Although parental control behaviors are more likely to be considered protective against risky sexual behavior, the relation between parental overprotection and risky sexual behavior is unclear. Furthermore, parental overprotection may influence peer selection and prosocial behaviors in emerging adults, which may in turn influence outcomes of risky sexual behavior, as suggested by primary socialization theory. Thus, the current study investigated the relations among paternal and maternal overprotection, emerging adult peer alienation, and risky sexual behavior, and expanded on these relations by examining gender effects of both parents and children. The sample consisted of 505 participants (228 males and 277 females) ranging in age from 18 to 25 years. Analyses were conducted with AMOS path analysis and indicated that peer alienation mediated the effect between both maternal and paternal perceived overprotection and risky sexual behavior, but more strongly for males, suggesting moderated mediation. Overall, parental overprotection may be protective against risky sexual behavior via pathways that are harmful such as peer alienation, thus recommending research continues to clarify the nuances of these relations.

Se sugiere que las conductas de control parental están relacionadas con consecuencias en los adultos emergentes, como el comportamiento sexual riesgoso. Aunque las conductas de control parental son más propensas a considerarse protectoras del comportamiento sexual riesgoso, la relación entre la sobreprotección de los padres y el comportamiento sexual riesgoso es confusa. Además, la sobreprotección de los padres puede influir en la elección del grupo de pares y las conductas prosociales de los adultos emergentes, que a su vez pueden influir en consecuencias de comportamiento sexual riesgoso, como lo sugiere la teoría de la socialización primaria. Por lo tanto, el presente estudio investigó las relaciones entre la sobreprotección materna y paterna, la alienación de los pares del adulto emergente y el comportamiento sexual riesgoso, y amplió estas relaciones analizando los efectos del género de los padres y los niños. La muestra consistió en 505 participants (228 hombres y 277 mujeres) de entre 18 y 25 años. Los análisis se realizaron con el análisis de ruta AMOS, e indicaron que la alienación de los pares medió el efecto entre la sobreprotección materna y paterna percibidas y el comportamiento sexual riesgoso, pero más marcadamente en los hombres, lo cual sugirió una mediación moderada. En general, la sobreprotección parental puede proteger contra la conducta sexual riesgosa a través de vías que son perjudiciales, como la alienación de los pares, por lo tanto, se recomienda continuar con la investigación a fin de aclarar los matices de estas relaciones.

Inhibition of motor neuron death in vitro and in vivo by a p75 neurotrophin receptor intracellular domain fragment.

The p75 neurotrophin receptor (p75(NTR); also known as NGFR) can mediate neuronal apoptosis in disease or following trauma, and facilitate survival through interactions with Trk receptors. Here we tested the ability of a p75(NTR)-derived trophic cell-permeable peptide, c29, to inhibit p75(NTR)-mediated motor neuron death. Acute c29 application to axotomized motor neuron axons decreased cell death, and systemic c29 treatment of SOD1(G93A) mice, a common model of amyotrophic lateral sclerosis, resulted in increased spinal motor neuron survival mid-disease as well as delayed disease onset. Coincident with this, c29 treatment of these mice reduced the production of p75(NTR) cleavage products. Although c29 treatment inhibited mature- and pro-nerve-growth-factor-induced death of cultured motor neurons, and these ligands induced the cleavage of p75(NTR) in motor-neuron-like NSC-34 cells, there was no direct effect of c29 on p75(NTR) cleavage. Rather, c29 promoted motor neuron survival in vitro by enhancing the activation of TrkB-dependent signaling pathways, provided that low levels of brain-derived neurotrophic factor (BDNF) were present, an effect that was replicated in vivo in SOD1(G93A) mice. We conclude that the c29 peptide facilitates BDNF-dependent survival of motor neurons in vitro and in vivo.