Are fathers involved in pediatric psychology research and treatment?

Background Recently, there has been a growing awareness of theimportance of the roles of fathers in understanding normativedevelopmental processes. Increased attention has been givento the roles of fathers in the area of clinical child researchand therapy. However, the presence of fathers in research andtreatment in pediatric psychology has not been fully examined.Objective To explore the status of including fathers in bothresearch and treatment in the area of pediatric psychology.Method An extensive review of published research. Results Thefindings suggest that pediatric psychology research lags evenfarther behind clinical child research in including fathersin research designs and analyzing for maternal and paternaleffects separately. There is also a concomitant lack of inclusionof fathers in family-based interventions in pediatric psychology.Conclusion These patterns are discussed, with an emphasis onstrategies to increase the inclusion of fathers in researchand treatment of pediatric psychology issues. Future directionsfor researchers and clinicians are also included.     

Are proteasomes involved in the formation of the kinetochore?

Proteasomes catalyse the degradation of proteins responsible for the regulation of mitosis enabling the cell to complete cell division. We have studied the effect of an inhibitor of the chymotrypsin-like activity of the proteasome on the trilaminar structure of the kinetochore in HeLa cells. Whereas a role for the proteasome in the degeneration of the kinetochore was predicted, we found instead that the inhibitor strongly retarded kinetochore development. We observed different developmental stages of the kinetochore from the fibrous ball of a prekinetochore to the mature kinetochore in one cell. The data presented here support the proposition that proteasomes are involved in kinetochore formation.accepted for publication by H. C. MacgregorDedicated to the memory of Prof. Dr. Daniel Mazia, a fatherly friend.     

Sleep duration in Mexican American children: Do mothers’ and fathers’ parenting and family practices play a role?

This study examined parenting styles, parenting practices and family practices that may be associated with weeknight sleep duration among 8‐ to 10‐year‐old Mexican American (MA) children. This cross‐sectional study of MA children used baseline data from a 2‐year cohort study of mother–child pairs (n = 308) with additional data on fathers (n = 166). Children's weeknight sleep duration was accelerometer estimated and averaged for 2 weeknights. Parents reported on their parenting styles and practices regarding food and family food‐related practices. Multivariable linear regression analysis was used to examine sleep duration with parenting styles and practices, and family practices, and adjusting for child gender and body mass index. Model 1 included mothers’ parenting styles and practices; Model 2 included both mothers’ and fathers’ parenting styles and practices. Children's average sleep duration was 9.5 (SD = 0.8) hr. Mothers who used pressure to encourage their children to eat and those who used food to control behavior had children with longer sleep duration (β = 0.21, p < 0.01; β = 0.15, p = 0.03, respectively). Mothers who reported their children ate dinner with the TV on and those who valued eating dinner as a family had children with shorter sleep duration (β = ?0.16, p = 0.01; β = ?0.18, p = 0.01, respectively). Fathers who restricted the amount of food their children ate had children with shorter sleep duration (β = ?0.27, p = 0.01). Mothers’ and fathers’ feeding practices, the child's eating dinner with the TV on, and valuing family dinners, played a role in children's weeknight sleep duration among Mexican American families. Parental feeding practices and family mealtime contexts may have an effect on children's weeknight sleep duration.     

Are impaired endothelial progenitor cells involved in the processes of late in-stent thrombosis and re-endothelialization of drug-eluting stents?

Drug-eluting stent (DES) now is the default selection for most of the interventional cardiologists. However, its benefits compromised by the stent-related thrombosis events. Given the catastrophic consequences, it is important to investigate possible mechanisms of stent thrombosis. The cause of stent thrombosis is multifactorial, and several stent-related and patient-related variables have been identified. The stent itself has components that may lead to thrombosis: the metal stent material, the polymer which houses the drug, and the actual cell-cycle inhibiting drugs. Most important the cell-cycle inhibitors (sirolimus and paclitaxel) reduce neointimal formation by impeding smooth muscle cells proliferation and migration, these drugs also impair the normal process of the injured arterial wall and cause delayed re-endothelialization [Tsimikas S. Drug-eluting stents and late adverse clinical outcomes. J Am Coll Cardiol 2006;47:2112-5; Colombo A, Drzewiecki J, Banning A, et al. Randomized study to assess the effectiveness of slow- and moderate-release polymer-based paclitaxel-eluting stent for coronary artery lesions. Circulation 2003;108:788-94; Kedia Gautam, Lee Michael S. Stent thrombosis with drug-eluting stents: a re-examination of the evidence. Catheter Cardiovasc Interv 2007;69:782-9] [1-3]. It has been proposed that bone marrow-derived endothelial progenitor cells may also be involved in re-endothelialization [Urao N, Okigaki M, Yamada H, et al. Erythropoietin-mobilized endothelial progenitors enhance reendothelialization via Akt-endothelial nitric oxide synthase activation and prevent neointimal hyperplasia. Circ Res 2006;98:1405-13; Griese DP, Ehsan A, Melo LG, et al. Isolation and transplantation of autologous circulating endothelial cells into denuded vessels and prosthetic grafts: implications for cell-based vascular therapy. Circulation 2003;108:2710-15] [4-5]. Interestingly, rapamycin inhibits proliferation, migration, and differentiation of human endothelial progenitor cells in vitro [Butzal M, Loges S, Schweizer M, et al. Rapamycin inhibits proliferation and differentiation of human endothelial progenitor cells in vitro. Exp Cell Res 2004;300:65-71; Chen TG, Chen JZ, Wang XX. Effects of rapamycin on number activity and eNOS of endothelial progenitor cells from peripheral blood. Cell Proliferat 2006;39:117-25]. We hypothesis that drugs loaded on DES may affect the number as well as the homing and proliferation of endothelial progenitor cells, thus further preventing proper endothelial healing, increasing platelet aggregation, which could lead to stent thrombosis.     

Are mechanically sensitive regulators involved in the function and (patho)physiology of cerebral palsy-related contractures?

Skeletal muscle tissue is mechanosensitive, as it is able to sense mechanical impacts and to translate these into biochemical signals making the tissue adapt. Among its mechanosensitive nature, skeletal muscle tissue is the largest metabolic organ of the human body. Disturbances in skeletal muscle mechanosensing and metabolism cause and contribute to many diseases, i.e. muscular dystrophies/myopathies, cardiovascular diseases, COPD or diabetes mellitus type 2. A less commonly focused muscle-related disorder is clinically known as muscle contractures that derive from cerebral palsy (CP) conditions in young and adults. Muscle contractures are characterized by gradually increasing passive muscle stiffness resulting in complete fixation of joints. Different mechanisms have been identified in CP-related contractures, i.e. altered calcium handling, altered metabolism or altered titin regulation. The muscle-related extracellular matrix (ECM), specifically collagens, plays a role in CP-related contractures. Herein, we focus on mechanically sensitive complexes, known as costameres (Cstms), and discuss their potential role in CP-related contractures. We extend our discussion to the ECM due to the limited knowledge of its role in CP-related contractures. The aims of this review are (1) to summarize CP-related contracture mechanisms, (2) to raise novel hypotheses on the genesis of contractures with a focus on Cstms, and (3) to stimulate novel approaches to study CP-related contractures.     

Practices and ethical concerns regarding preimplantation diagnosis. Who regulates preimplantation genetic diagnosis in Brazil?

Preimplantation genetic diagnosis (PGD) was originally developed to diagnoseembryo-related genetic abnormalities for couples who present a high risk of aspecific inherited disorder. Because this technology involves embryo selection, themedical, bioethical, and legal implications of the technique have been debated,particularly when it is used to select features that are not related to seriousdiseases. Although several initiatives have attempted to achieve regulatoryharmonization, the diversity of healthcare services available and the presence ofcultural differences have hampered attempts to achieve this goal. Thus, in differentcountries, the provision of PGD and regulatory frameworks reflect the perceptions ofscientific groups, legislators, and society regarding this technology. In Brazil,several texts have been analyzed by the National Congress to regulate the use ofassisted reproduction technologies. Legislative debates, however, are not conclusive,and limited information has been published on how PGD is specifically regulated. Thecountry requires the development of new regulatory standards to ensure adequateaccess to this technology and to guarantee its safe practice. This study examinedofficial documents published on PGD regulation in Brazil and demonstrated how littledirect oversight of PGD currently exists. It provides relevant information toencourage reflection on a particular regulation model in a Brazilian context, andshould serve as part of the basis to enable further reform of the clinical practiceof PGD in the country.     

HIGH‐RISK HPV testing as the primary screening method in an organized regional screening program for cervical cancer: the value of HPV16 and HPV18 genotyping?

Since 2012, testing high‐risk (HR)HPV has been used as the primary screening test for women ≥35 years attending the organized cervical cancer screening program in the city of Tampere. We evaluated the contribution of HPV16/18 genotyping. Data from 2012 and 2013, and the follow‐up samples in 2013 and 2014, respectively, were analyzed. Abbott RealTime High‐Risk HPV test detecting 14 HRHPV genotypes combined with concurrent genotyping for HPV16 and HPV18 was used. HPV was positive in 794 samples out of 11 346 HPV tested women (7%). HPV16/18 was represented in 22% of HPV‐positive cases. Negative cervical cytology (NILM) was reported in 51% of HPV‐positive samples. HPV16/18 genotype was accompanied with 50% of HSIL/ASC‐H cases. The predominance of HPV16/18 in higher grade lesions was even more evident in cervical biopsies as 57% of CIN3 cases were associated with HPV16/18, and only 20% of carcinomas were associated with nonspecified high‐risk (NSHR) genotypes. In agreement with previous studies HPV16/18 genotypes caused higher grade cytological and histological changes/pathologies than NSHR genotypes in primary screening. Nevertheless, the majority of HRHPV genotypes detected in the screened population were nonHPV16/18, and especially within persistent infections, precancerous lesions were found also among women with NSHR genotypes.     

What predicts patients’ perceptions of improvement in insomnia?

Although there has been considerable research into the effectiveness of individual cognitive behavioral treatment for chronic insomnia, less is known about patients' perceptions of what constitutes actual improvement. This study utilized 70 outpatients (mean age = 49.7 years, SD = 12.0) with insomnia who completed a 6-week cognitive behavioral group for sleep. Participants completed a number of primary (Pittsburgh Sleep Quality Index) and secondary measures (the Dysfunctional Beliefs about Sleep Scale, Insomnia Severity Index, Beck Depression Inventory, Penn State Worry Questionnaire) at pre- and post-treatment. Perceived improvement was measured using the Clinical Global Improvement Scale (CGI). Results were analyzed using a combination of Logistic Regression analysis and receiver operating curve characteristic analysis (ROC). Results demonstrated that sleep quality and sleep duration were the most sensitive primary measures, or best predicted perceived improvement, whereas sleep efficiency was the most specific primary measure, or best predicted perceived lack of improvement (defined as only mild improvement). Of the secondary measures, results showed that daytime impairment was the most sensitive predictor of perceived improvement and that mood was the most specific predictor of perceived lack of improvement. Implications of these findings are that sleep quality, sleep duration, and sleep efficiency may offer different types of information and the choice of measure for predicting global improvement in insomnia will depend on the needs of the researcher/clinician.     

Are basophil histamine release and high affinity IgE receptor expression involved in asymptomatic skin sensitization?

BACKGROUND: Immunoglobulin (Ig)E-sensitized persons with positive skin prick test, but no allergy symptoms, are classified as being asymptomatic skin sensitized (AS). The allergic type 1 disease is dependant on IgE binding to the high affinity IgE-receptor (FcepsilonRI) expressed on basophils and mast cells. However, a relationship between the AS status and FcepsilonRI has not been investigated. We aimed to characterize basophils from AS by looking at histamine release (HR) (sensitivity and reactivity) and the FcepsilonRI molecule, and compare it with nonatopic (NA) or allergic (A) persons. METHODS: Blood was obtained from NA (n = 14), grass and/or birch A persons (n = 17) and mono-sensitized grass or birch pollen AS (n = 12). The basophil sensitivity and reactivity were examined by anti-IgE triggered HR. Surface expression of FcepsilonRI and IgE were measured by flow cytometry, FcepsilonRIalpha protein was identified using a radioimmunoassay and Western blot. mRNA coding for the classic FcepsilonRIbeta-chain and the truncated form (FcepsilonRIbetaT) were determined by real-time PCR. RESULTS: The AS group was less reactive than NA or A persons when triggered by anti-IgE and had a significant higher number of nonresponders. However, there was no difference in sensitivity among the three groups and furthermore; the groups did not vary in FcepsilonRI- and IgE-surface expression, FcepsilonRIalpha-protein level or beta/betaT ratio. CONCLUSION: Basophils from AS persons are less reactive and include more nonresponders than basophils from NA and A persons, but do not differ regarding the FcepsilonRI molecule.     

Management of colorectal cancer: A role for genetics in prevention and treatment?

Colorectal cancer remains one of the most common cancers in the Western world and amongst the top three causes of cancer morbidity and death. Cancer is caused by genetic mutations, but currently there is little use of genetic information in the clinic with the exception of establishing germline mutations for the uncommon predisposing syndromes. Rapid advances in technologies allowing high throughput analysis of germline and somatic mutations raises the possibility that genetics will find a major role in the clinic distinguishing individuals at low to high risk of cancer, allowing early intervention and stratification of cancers based on mutational pathways for therapeutic interventions. In the future, this will lead to treatment regimes tailored to the individuals and their tumor. Here, we summarize the genetics underlying colorectal cancer and the future role of genetics in prevention, diagnosis, classification and treatment.     

Karyotype and age in acute myeloid leukemia. Are they linked?

A novel hierarchical cytogenetic classification for acute myeloid leukemia (AML) has been developed. Patients with successful cytogenetics and a diagnosis of AML were categorized into four mutually exclusive karyotype groups: normal, translocation, deletion and trisomy. Patients with more than one chromosomal abnormality were classified using the hierarchy: established translocation>established deletion>established trisomy>non-established translocation>non-established deletion>non-established trisomy. A total of 593 AML patients from a large population-based case-control study of acute leukemia were classified according to their diagnostic karyotype. The four karyotype groups showed different age distributions. Overall the frequency of patients increased with age as did the frequency of patients with a deletion, trisomy or normal karyotype. Although the increase of patients with age was much sharper for patients with a deletion. In contrast, the distribution of patients with a translocation was roughly constant with age. We concluded that there was a link between karyotype and the age of the patient at diagnosis. Furthermore, two karyotype groups, translocations and deletions, may define disease entities with different etiologies. This novel cytogenetic classification will allow other studies to examine whether AML cases with very different types of chromosomal abnormality have the same etiology.     

Are the effects of training on fat metabolism involved in the improvement of performance during high-intensity exercise?

The objective of the present study was to relate changes in certain muscle characteristics and indicators of metabolism in response to endurance training to the concomitant changes in time to exhaustion (T_lim) at a work rate corresponding to maximal oxygen uptake Eight healthy sedentary subjects pedalled on a cycle ergometer 2 h a day, 6 days a week, for 4 weeks. Training caused increases in O_2peak (by 8%), T_lim (from 299±23 s before to 486±63 s after training), citrate synthase and 3-hydroxyl-acyl-CoA dehydrogenase (HAD) activities (by 54% and 16%, respectively) and capillary density (by 31%). Decreases in activity of lactate dehydrogenase (LDH) and muscle type of LDH (by 24% and 28%, respectively) and the phosphofructokinase/citrate synthase ratio (by 37%) were also observed. Respiratory exchange ratio (RER) tended to be lower (P<0.1) at all relative work rates after training while the corresponding ventilation rates ( E) were unchanged. At the same absolute work rate, RER and E were lower after training (P<0.05). The improvement of T_lim with training was related to the increases in HAD activity (r=0.91, P=0.0043), and to the decreases in RER calculated for Pa_peak (r=0.71, P=0.0496). The present results suggest that the training-induced adaptations in fat metabolism might influence T_lim at a work rate corresponding to O_2peak and stimulate the still debated and incompletely understood role of fat metabolism during short high-intensity exercise     

To tell or not to tell? A systematic review of ethical reflections on incidental findings arising in genetics contexts

Any test that produces visual images or digital or genetic sequences will tend to produce incidental findings because more will be visible than what was originally sought. We conducted a systematic review of the ethical reasons presented in the literature for and against the disclosure of incidental findings arising in clinical and research genetics contexts. A search of electronic databases resulted in 13 articles included for systematic review. Articles presented reasons for and against disclosure, and reasons for proceeding with caution when making decisions about disclosure. One major recommendation of the reviewed articles is in favor of qualified disclosure: incidental findings with confirmed clinical utility where there is the possibility of treatment or prevention should be disclosed, with exceptions. A second type of recommendation is that disclosure should proceed with caution, especially in the context of new genetic technologies and genetic testing involving minors. It is also recommended that the number of possible incidental findings be limited even before genetic testing is carried out. Such a policy, which we advocate, would show preference for non-disclosure.     

A gift or a yoke? Women’s and men’s responses to genetic risk information from BRCA1 and BRCA2 testing

This qualitative study explored the impact of genetic risk information from BRCA1/2 testing on individuals' subjective understandings of self and self-identity. In-depth interviews were conducted with 39 participants (34 women and 5 men) who had received test results from BRCA1/2 testing. Themes emerging from qualitative data analysis revealed that participants linked their positive results to becoming more aware of their physical selves (embodied self), their selves in relation to family (familial-relational self) and their selves in relation to wider kinship or social groups (social self). Genetic information was generally viewed as enabling; it allowed participants to take measures (surveillance or prophylactic surgery) to confront the disease. However, for a small minority of women, knowledge about their genetic risk had a profound and limiting effect on their agency. Rather than giving them a sense of control, they saw little opportunity to fight the disease. For a few people, identification of a genetic mutation thrust them into an uncertain state, that is in a position of being neither ill nor completely well. In one case, BRCA information led to a disruption of social identity. Further work is needed to assess the impact of age and life stage on psychological responses to genetic information on cancer susceptibility.     

A decade of acceptable autopsy rates. Does concordance of clinician and pathologist views explain relative success?

In an attempt to better understand the basis and significance of an annual autopsy rate consistently over 45% for the past decade, we recently investigated the attitudes and practices of 36 pathologists and 176 clinicians in our institution with respect to the function of the autopsy service and the utility of the autopsy. The autopsy report was "not used in a consistent manner" by 57% of clinical respondents. Several clinicians thought that autopsy reports were too long (20%) and too slow (38%), but not with the frequency that pathologists did, 73% and 58%, respectively. Significantly more pathologists than clinicians believed autopsy rates have fallen over the past 20 years because (1) people think that everything about the deceased is already known, (2) medical students are poorly educated about the autopsy, (3) pathologists have diminished interest, (4) physicians fear litigation, (5) physicians fear "being wrong," (6) pathologists lack financial incentives, and (7) Joint Commission on Accreditation of Healthcare Organizations requirement is not in place. Perceptions regarding the frequency of major discrepancies between clinical and autopsy findings were comparable, 17% and 13%, for pathologists and clinicians, respectively. Our "high" institutional autopsy rate does not reflect concordance of perceptions expressed by clinicians and pathologists and, thus, other factors may be important in the maintenance of an acceptable rate.