Parent coaching increases the parents' capacity for reflection and self-evaluation: results from a clinical trial in autism.

Family-centered parent coaching interventions in autism strive to encourage family engagement and support parent reflection and self-evaluation. This includes the parents' capacity to: (1) carefully observe the child's behavior; (2) reflect upon the child's thoughts, motives, and feelings; (3) consider links between the child's internal experiences and observable behavior; and (4) grapple with the complex interplay among the child's experiences and behaviors, contextual factors, parenting strategies, as well as parental goals and emotions. The current study reports data from a clinical trial of Focused Playtime Intervention (FPI), a parent coaching intervention targeting responsive parental behaviors and child communication. Seventy children with autism between 2 and 6 years and their parents were randomly assigned to participate in FPI for 12 weeks or an active control intervention. The Insightfulness Assessment was administered and used (a) to classify parents' baseline capacity for reflection and self-evaluation as either established (i.e., positively insightful) or emerging, and (b) to capture longitudinal change in the parents' capacity between baseline, exit (~5 months after baseline), and follow up (~14 months after exit) using a dimensional composite subscale score. Results revealed a significant treatment effect of FPI on growth in the parents' capacity for reflection and self-evaluation, conditional on the parents' classification at baseline. That is, parents whose capacity for reflection and self-evaluation was classified as emerging at baseline (n = 42) showed higher rates of growth when assigned to FPI, compared to the control condition. A similar treatment effect was not found for parents whose baseline capacity for reflection and self-evaluation was classified as established (i.e., positively insightful). This is the first study to show that a family-centered parent coaching intervention effectively increases the capacity for reflection and self-evaluation in parents of young children with autism. This capacity may enable parents to adapt and implement intervention strategies flexibly across contexts, daily routines, and interactions.

Assessment of EndoPAT scores in men with vasculogenic and non-vasculogenic erectile dysfunction.

PURPOSE: The role of endothelial function testing using peripheral artery tonometry (PAT) in the evaluation of ED is not well established. Endothelial dysfunction is expected to be more common in men presenting with general or vasculogenic ED, compared with men who develop ED after prostatectomy. This study evaluated whether PAT could help identify men in whom endothelial cell dysfunction was the underlying cause of ED. MATERIALS AND METHODS: A chart review of 194 men with general ED and 98 men with postprostatectomy ED was performed to abstract data on demographics, medical comorbidities, SHIM-5 scores and EndoPAT scores. Patients with preoperative ED were excluded. Statistical analysis using Student's t-test and Chi-squared analysis was performed to compare the two groups of men with respect to these variables. RESULTS: EndoPAT scores were not significantly different between men with general vs. postprostatectomy ED (1.97 vs. 2.08, p = 0.074). There was no relationship between EndoPAT and SHIM-5 scores in the general ED cohort. The prevalence of hypertension, hyperlipidaemia and cardiovascular (CV) disease was similar between the two groups, but diabetes and hypogonadism were more prevalent in men with general ED (21% vs. 9%, and 28% vs. 7%, p < 0.015). Overall, EndoPAT scores in postprostatectomy men with at least one risk factor were not significantly different compared with men with general ED with the same comorbidity, or a combination of two or more comorbidities. CONCLUSIONS: The value of EndoPAT testing in the clinical evaluation of ED patients is questionable.

Can family affectedness inform infant sibling outcomes of autism spectrum disorders?

BACKGROUND: Difficulties in communication and reciprocal social behavior are core features of autism spectrum disorders (ASD) and are often present, to varying degrees, in other family members. This prospective longitudinal infant sibling study examines whether social-communicative features of family members may inform which infants are at increased risk for ASD and other developmental concerns. METHOD: Two hundred and seventeen families participated in this study. Infant siblings were recruited from families with at least one older child diagnosed with an ASD (n = 135) or at least one typically developing older child (n = 82). Families completed the Social Responsiveness Scale to assess social and communication features of the broader autism phenotype (BAP), sometimes called quantitative autistic traits (QAT). Family affectedness was assessed in two ways: categorically, based on number of affected older siblings (i.e., typical, simplex, multiplex risk groups) and dimensionally, by assessing varying degrees of QAT in all family members. Infant siblings were assessed at 36 months of age and completed the Autism Diagnostic Observation Schedule and the Mullen Scales of Early Learning. RESULTS: In structural equation models, comparisons between multiplex, simplex and typical groups revealed the highest rates of QAT in the multiplex group followed by the simplex and typical groups. Infant sibling outcomes were predicted by gender, family risk group, proband QAT, and additional sibling QAT. CONCLUSIONS: Replicating previous cross-sectional and family history findings, the present study found elevated social and communication features of the BAP in siblings and fathers of ASD families, but not in mothers. While social and communication features of the BAP in mothers, fathers, and undiagnosed siblings did not predict infant sibling outcomes, having more than one affected older sibling did. Infant siblings from multiplex families were at significantly higher risk for ASD than infant siblings from simplex families in this sample.

The neural basis of perceptual learning.

Perceptual learning is a lifelong process. We begin by encoding information about the basic structure of the natural world and continue to assimilate information about specific patterns with which we become familiar. The specificity of the learning suggests that all areas of the cerebral cortex are plastic and can represent various aspects of learned information. The neural substrate of perceptual learning relates to the nature of the neural code itself, including changes in cortical maps, in the temporal characteristics of neuronal responses, and in modulation of contextual influences. Top-down control of these representations suggests that learning involves an interaction between multiple cortical areas.

Learning to find a shape.

We studied the transition of stimuli from novel to familiar in visual search and in the guidance of attention to a particular object. Ability to identify an object improved dramatically over several days of training. The learning was specific for the object's position in the visual field, orientation and configuration. Improvement was initially localized to one or two positions near the fixation spot and then expanded radially to include the full area of the stimulus array. Characteristics of this learning process may reflect a shift in the cortical representation of complex features toward earlier stages in the visual pathway.

High-quality human and rat spermatozoal RNA isolation for functional genomic studies.

Sperm RNA is a sensitive monitoring endpoint for male reproductive toxicants, and a potential biomarker to assess male infertility and sperm quality. However, isolation of sperm RNA is a challenging procedure due to the heterogeneous population of cells present in the ejaculate, the low yield of RNA per spermatozoon, and the absence of 18S and 28S ribosomal RNA subunits. The unique biology of spermatozoa has created some uncertainty in the field about RNA isolation methods, indicating the need for rigorous quality control checks to ensure reproducibility of data generated from sperm RNA. Therefore, we developed a reliable and effective protocol for RNA isolation from rat and human spermatozoa that delivers highly purified and intact RNA, verified using RNA-specific electrophoretic chips and molecular biology approaches such as RT-PCR and Western blot analysis. The sperm RNA isolation technique was optimized using rat spermatozoa and then adapted to human spermatozoa. Three steps in the sperm isolation procedure, epididymal fluid collection, sperm purification, and spermatozoon RNA extraction, were evaluated and assessed. The sperm RNA extraction methodology consists of collection of rat epididymal fluid with repeated needle punctures of the epididymis, somatic cell elimination using detergent-based somatic cell lysis buffer (SCLB) and the use of RNA isolation Kit. Rat sperm heads are more resistant to disruption than human spermatozoa, necessitating the addition of mechanical lysis with microbeads and heat in the rat protocol, whereas the human sperm protocol only required lysis buffer. In conclusion, this methodology results in reliable and consistent isolation of high-quality sperm RNA. Using this technique will aid in translation of data collected from animal models, and reproducibility of clinical assessment of male factor fertility using RNA molecular biomarkers.

A lateral-to-mesial organization of human ventral visual cortex at birth.

In human adults, ventral extra-striate visual cortex contains a mosaic of functionally specialized areas, some responding preferentially to natural visual categories such as faces (fusiform face area) or places (parahippocampal place area) and others to cultural inventions such as written words and numbers (visual word form and number form areas). It has been hypothesized that this mosaic arises from innate biases in cortico-cortical connectivity. We tested this hypothesis by examining functional resting-state correlation at birth using fMRI data from full-term human newborns. The results revealed that ventral visual regions are functionally connected with their contra-lateral homologous regions and also exhibit distinct patterns of long-distance functional correlation with anterior associative regions. A mesial-to-lateral organization was observed, with the signal of the more lateral regions, including the sites of visual word and number form areas, exhibiting higher correlations with voxels of the prefrontal, inferior parietal and temporal cortices, including language areas. Finally, we observed hemispheric asymmetries in the functional correlation of key areas of the language network that may influence later adult hemispheric lateralization. We suggest that long-distance circuits present at birth constrain the subsequent functional differentiation of the ventral visual cortex.

Intra- and inter-individual differences in human sperm DNA methylation.

There is growing evidence that sperm DNA methylation is important in maintaining proper sperm health and function. Previous studies have associated sperm DNA methylation levels with sperm quality and function, however, little is known regarding the intra- and inter-individual variability in sperm methylation levels. This study characterizes this variation. Sperm epigenetic differences between successive semen samples from 12 patients were examined to identify the intra- and inter-individual differences globally across the genome, and in specifically defined genomic regions using the Illumina Infinium HumanMethylation450 BeadChips. Methylation analysis identified a bimodal distribution in the methylation levels that were non-uniformly distributed across the different genomic regions. The methylation levels were highly correlated in both the intra- and inter-individual comparisons. The intra-individual methylation levels were more highly correlated than the inter-individual comparison both globally and across the defined genomic regions, demonstrating that sperm DNA methylation levels are relatively stable between semen sample collections.

Iridium(iii)-bis(imidazolinyl)phenyl catalysts for enantioselective C-H functionalization with ethyl diazoacetate.

The intermolecular enantioselective C-H functionalization with acceptor-only metallocarbenes is reported using a new family of Ir(iii)-bis(imidazolinyl)phenyl catalysts, developed based on the interplay of experimental and computational insights. The reaction is tolerant of a variety of diazoacetate precursors and is found to be heavily influenced by the steric and electronic properties of the substrate. Phthalan and dihydrofuran derivatives are functionalized in good yields and excellent enantioselectivities.

Response of rat mammary gland transferrin receptors to maternal dietary iron during pregnancy and lactation.

Mammalian milk iron (MFe) concentration decreases during lactation. In human attempts to increase MFe through supplementing the mother with iron during lactation have failed and no correlation between maternal iron status or intake and MFe has been determined, suggesting a regulatory mechanism. In contrast MFe in lactating rats can be affected by very high or low amounts of ingested iron. We previously described a transferrin receptor (TfR) mechanism that controls iron entry into rat mammary tissue. In this study lactating rats were used to determine effects of varying dietary iron during gestation and lactation on mammary TfR and MFe. Dams fed low-iron diets had a small increase in TfR, lower hematological indices (p less than 0.005), and lower MFe (p less than 0.005) than did controls or dams fed high iron. Dams fed the high-iron diet had a significant increase in TfR without a concomitant increase in MFe. There was no correlation between MFe and TfR. These findings suggest that control of MFe lies after iron entry into mammary tissue.

Relationships between morbidity and development in mildly to moderately malnourished Kenyan toddlers.

This study explored the extent to which morbidity in 110 mildly to moderately malnourished Kenyan toddlers was associated with developmental outcomes. Morbidity information was collected from the 18th to 30th months. Concurrent assessments of vocalization, play, and performance on the Bayley scales were obtained. At 5 years, a follow-up battery of cognitive tests was administered. Female toddlers who suffered more illness generally performed less well on developmental measures than their healthier female peers. These children vocalized and played less and performed less well on the Bayley Mental scales at 30 months and on the cognitive battery at 5 years. For the boys, development was largely independent of morbidity. Morbidity was related to patterns of care giving for both boys and girls, but it was not associated with socioeconomic status or food intake. However, girls who were ill more often were shorter and lighter. Relations between morbidity and development in the girls remained statistically significant when other variables, which were also related to development (such as care giving, socioeconomic status, parental IQ and literacy, food intake, and anthropometry) were considered. This suggests that morbidity, in these female toddlers, had an effect on development above and beyond other variables typically associated with malnutrition.

Alcohol use in primiparous women older than 30 years of age: relation to infant development.

The effects of maternal alcohol use on mental development, growth, and dysmorphogenesis was studied in a sample of 1-year-old infants born to elderly primiparous mothers. Alcohol intake was measured using Jessor's AA score and a simple count of maximum number of drinks consumed in one day. Infant cognition was assessed using the Bayley Scale of Mental Development. Alcohol levels prior to, during, and following pregnancy were obtained. Alcohol intake was greatly reduced during pregnancy, returning to pregnancy levels following birth. A significant linear relationship between drinking prior to pregnancy and infant mental development was found. The average mental development score of infants whose mothers consumed less than or equal to 3, 3.3 to 29.7, or greater than or equal to 30 mL (less than or equal to 0.10, 0.11 to 0.99, or greater than or equal to 1.0 average fluid ounces) of absolute alcohol per day was 115, 108, and 95, respectively. Maximum number of drinks consumed in a day related to physical anomalies. No alcohol measure was significantly correlated with condition at birth, postnatal illness, or growth parameters of height, weight, and head circumference at 1 year. Deficits found were less pronounced than those reported in infants with fetal alcohol syndrome.

Social attachments in autistic children.

Social responses of young autistic children to separation from and reunion with their caregivers did not differ from the social responses to similar situations of young mentally retarded nonautistic children. Most autistic children directed more social behaviors to their caregivers than to strangers and increased their preferential behavior after separation. Individual differences in social responses were not associated with the level of representational skills shown by the autistic children.

Endocrine evaluation of infertile men.

OBJECTIVES: To determine the incidence and type of endocrinologic abnormalities in men undergoing infertility evaluations and the most appropriate testing to detect them. METHODS: A retrospective review of consecutive patients attending two infertility centers was performed. Results of endocrine testing were compared to medical history and physical and laboratory findings to determine whether endocrinologic screening could be limited to a specific subpopulation. RESULTS: Only 99 of the 1035 patients (9.6%) had abnormal endocrine studies upon repetitive testing. The majority of these patients had an isolated elevation of serum follicle stimulating hormone (FSH) levels. Only 1.7% had a clinically significant endocrinopathy that would have had an effect upon disease management. Screening with serum testosterone and FSH levels alone was just as effective as a complete hormonal panel of testosterone, FSH, luteinizing hormone, and prolactin for the detection of clinically significant endocrinopathy. Only 1 patient with a clinically significant endocrinopathy would not have been identified if hormonal screening was limited to only those patients with a sperm density of less than 10 x 10(6)/mL. CONCLUSIONS: Endocrinopathies are a rare cause of male infertility. Endocrine screening of men with sperm counts of less than 10 million/mL with serum testosterone and FSH levels alone will detect the vast majority of clinically significant endocrinopathies.

Incidence of varicoceles in men with primary and secondary infertility.

OBJECTIVES: To determine whether varicoceles are more prevalent in men with secondary infertility than in men with primary infertility. METHODS: The records of 2188 consecutive men attending three infertility centers were reviewed to determine the incidence of varicoceles in men with primary and secondary infertility. In addition, other factors affecting both male and female infertility were assessed in these patients. RESULTS: The incidence of varicoceles was not significantly different between the 1447 men with primary infertility versus the 741 men with secondary infertility: 44% and 45%, respectively. The incidence of vasal agenesis was significantly greater in men with primary infertility (P < 0.001). In addition, the female partner was significantly older in couples with secondary infertility (P < 0.001). CONCLUSIONS: These findings do not support the conclusion that varicoceles have a progressive adverse effect on fertility over time and suggest that further study is needed to determine whether varicocele repair is indicated in patients with normal semen parameters.

Effect of level of anastomosis and quality of intraepididymal sperm on the outcome of end-to-side epididymovasostomy.

OBJECTIVES: Epididymovasostomy is commonly performed at the most distal site of the epididymis where whole sperm are present within the lumen, regardless of their motility status. Although more fresh and motile sperm can be found more proximally within the epididymis, it is believed that the outcome of epididymovasostomy is better more distally. Because the current results of epididymovasostomy are far from perfect, it would be ideal to be able to harvest motile sperm for cryopreservation at the time of surgery in case the patient remains azoospermic postoperatively. The objective of this study was to determine the effect of the level of epididymal anastomosis and quality of sperm on the outcome of surgery. METHODS: An end-to-side epididymovasostomy was performed on 131 azoospermic men with a mean age of 39 years and a mean obstructive interval of 18 years. The etiology of obstruction was vasectomy in 48%, infectious in 19%, congenital in 20%, and unknown in 13%. The average duration of follow-up was 32 months. The overall patency rate was 67% and pregnancy rate was 27%. Subgroups of patients with an anastomosis to the same level of the epididymis on all functional sides were identified as follows: caput (56), corpus (28), and cauda (13). These groups were compared in regard to the presence of motile sperm within the epididymal lumen at the time of surgery, patency rates, postoperative semen quality, and pregnancy rates. RESULTS: Motile sperm were present more often in both the caput (54%) and corpus (61%) than in the cauda epididymis (25%) (P < 0.05). The patency rates for the three subgroups were not significantly different. The postoperative total motile sperm count and pregnancy rate for the corpus epididymis (13 x 10(6) and 45%) was significantly (P < 0.05) better than for the caput (4.4 x 10(6) and 22%) but no different than that of the cauda (10 x 10(6) and 23%). The patency and pregnancy rates for anastomoses performed at levels demonstrating motile sperm were not significantly better than at sites with nonmotile sperm, but the postoperative total motile sperm count was better (P < 0.05). CONCLUSIONS: The results of this study suggest that the outcomes of epididymovasostomy to the corpus and cauda epididymis are roughly equivalent and superior to the caput. Therefore, it may be reasonable to move more proximally from the cauda to corpus in the search for motile sperm for cryopreservation during an end-to-side epididymovasostomy. In contrast, moving from the corpus to the caput epididymis has a significant adverse effect upon outcome; it is, therefore, not worthwhile to search for viable sperm for cryopreservation in this clinical setting.

Laparoscopic versus subinguinal varicocelectomy: a comparative study.

OBJECTIVE: To determine the relative advantages of the laparoscopic approach to varicocelectomy, postoperative morbidity and pain in patients undergoing subinguinal varicocelectomies were compared with that of patients undergoing laparoscopic varicocele repairs. DESIGN: Retrospective study of concurrent groups of patients undergoing laparoscopic or open subinguinal varicocele repairs. SETTING: Tertiary teaching hospital. PATIENTS: Forty-seven patients with primary or secondary infertility. INTERVENTIONS: Patients were offered a choice between a laparoscopic or open subinguinal varicocele repair. MAIN OUTCOME MEASURES: The total number of pain pills used, the number of days of analgesics, and the number of days off from work after surgery were recorded. RESULTS: Fourteen patients underwent laparoscopic varicocelectomies, and 33 patients underwent subinguinal varicocelectomies. Analgesic use by the laparoscopic patients was no different from that of the subinguinal patients. The length of time off from work was significantly longer for the laparoscopic patients (6.4 days) as compared with the time off from work for the patients who underwent subinguinal varicocele repairs (2.6 days). CONCLUSION: The subinguinal varicocele repair performed with local anesthesia is a safe, low morbid technique offering a quicker recovery period than laparoscopic approaches. Although laparoscopic repairs may offer a shorter recovery period when compared with standard inguinal varicocelectomies, this is not the case when compared with subinguinal approaches.

Relationship of milk iron and the changing concentration of mammary tissue transferrin receptors during the course of lactation.

The concentration of iron in all mammalian milks falls during lactation while the infant's iron requirement increases. Little is known, however, about the entry of iron into milk. Recently, transferrin receptors have been identified on lactating rat mammary plasma membranes, which may regulate iron entry into mammary tissue, potentiating its availability for subsequent transport into milk. This study was conducted to determine what relationship exists between the declining concentration of milk iron and the transferrin receptor concentration during various stages of lactation. Minimal transferrin receptors were detected in nulliparous rats. Total mammary transferrin receptor content increased during early and mid-lactation while milk iron concentration decreased. The continued appearance of high levels of transferrin receptors throughout lactation, without a concomitant increase in milk iron concentration, suggests a need for iron for functions other than cellular growth or secretion into milk to meet infant needs.

Characterization of transferrin receptors on plasma membranes of lactating rat mammary tissue.

Little is known about the transport of iron into the mammary secretory cell and the process of milk iron secretion. The concentration of iron in milk is remarkably unaffected by maternal iron status, suggesting that the uptake of iron into the mammary gland is regulated. It is known that iron enters other cells via transferrin receptor-mediated endocytosis. This study was designed to isolate and characterize the mammary gland transferrin receptor in lactating rat mammary tissue using immunochemical techniques. The existence of functional mammary gland transferrin receptors in lactating rodents was demonstrated using radiolabel-binding techniques. Isolation of mammary transferrin receptors by affinity chromatography was confirmed using immunoelectrophoresis and slot blot analysis. The intact transferrin receptor was found to have a molecular weight of 176 kd as determined by Western blotting followed by scanning densitometry. Reduction of the receptor with beta-mercaptoethanol gave a molecular weight of 98 kd. An additional immunoreactive band of 135 kd was observed. The presence of transferrin receptors in normal lactating rat mammary tissue is likely to explain iron transport into mammary tissue for both cellular metabolism and milk iron secretion.

Parental perception of emotional expressiveness in children with autism.

Parents' perceptions of their children's emotional expressiveness, and possible bases for these perceptions, were investigated in a study comparing older, nonretarded autistic and normal children and in another study comparing young autistic, mentally retarded, and normal children. Both groups of autistic children were perceived as showing more negative emotion and less positive emotion than comparison children. In the younger sample, parental perceptions correlated with the children's attention and responsiveness to others' displays of emotion in 2 laboratory situations. Findings contradict the view that autism involves the "absence of emotional reaction" (American Psychiatric Association, 1987, p. 35).