Psychological aspects of being a parent of an individual with Rett syndrome: A scoping review.

BACKGROUND: Rett syndrome (RTT) causes multiple disabilities with a lifelong need for substantial care, placing a tremendous lifelong responsibility on the parents. Parenting an individual with RTT can therefore be challenging. Research on the psychological aspects of parenting individuals with RTT is limited and unclear. We aimed to identify and map the existing literature on this subject. METHOD: A scoping review was conducted with systematic searches in PubMed, PsycINFO and CINAHL. RESULTS: Eighteen studies were included. Negative and positive psychological aspects were described with the majority focusing on the negative. Three factors seemed to especially affect the parents: severity of the diagnosis, time (increasing age of parents or individual with RTT; years of caretaking), work-status of the mother. CONCLUSIONS: Seemingly, parents are highly affected; however, the literature is scarce and has several gaps. Future research should include older parents, fathers, parents of individuals living in group homes, and positive aspects.

Rett Syndrome Behaviour Questionnaire in Children and Adults With Rett Syndrome: Psychometric Characterization and Revised Factor Structure.

Rett syndrome (RTT) is a severe neurodevelopmental disorder associated with multiple neurobehavioral abnormalities. The Rett Syndrome Behaviour Questionnaire (RSBQ) was developed for pediatric RTT observational studies. Because its application has expanded to adult and interventional studies, we evaluated the RSBQ's psychometric properties in six pediatric (n = 323) and five adult (n = 309) datasets. Total and General Mood subscale scores had good reliability. Clinical severity had no influence on RSBQ scores. Exploratory and confirmatory factor analyses yielded 6 pediatric and 7 adult clinically relevant and psychometrically strong factors including the original Breathing Problems and Fear/Anxiety subscales and the novel Emotional and Disruptive Behavior subscale composed of items from the original General Mood and Nighttime Behaviours subscales. The present findings support additional evaluations and improvements of an important RTT behavioral measure.

Changes of Physical Function and Quality of Life in Patients with Type 2 Diabetes after Exercise Training in a Municipality or a Hospital Setting.

INTRODUCTION: The aim was to compare changes in physical function and quality of life (QOL) after an exercise training programme to patients with type 2 diabetes mellitus (T2DM) in a municipality and a hospital setting and to compare the patients' physical function and QOL with an age- and sex-matched general population. METHODS: Patients with T2DM were stratified to exercise training in a municipality (n = 26) or a hospital (n = 46), respectively. The training was one hour twice weekly for 12 weeks. The outcomes were physical function (30 sec chair stand test (CST)) and QOL (using the SF-36). The data for the general population were collected from previous reference studies. RESULTS: Fifty-one (71%) participants completed the intervention. The CST results improved in both groups with no difference between the municipality and hospital groups (1.6 [0.1; 3.1] vs. 3.5 [2.3; 4.8] no., respectively, p = 0.062). The QOL scales physical function and general health increased more in the municipality group than in the hospital group (10.5 [2.8; 18.2] vs. -1.2 [-7.9; 5.5], respectively, p = 0.031, and 8.3 [2.3; 14.4] vs. -0.2 [-5.6; 5.1], respectively, p = 0.042). Dropout (n = 21) during the intervention was associated with reduced QOL at baseline. The patients' CST results at baseline were reduced compared to the general population (11.8 ± 3.5vs.18.9 ± 3.3, respectively, p < 0.001). All QOL scales apart from social function were reduced in the patients compared to the general population. CONCLUSION: Patients in a 12-week exercise training programme in a hospital or a municipality setting had significantly lower QOL compared to an age- and sex-matched population sample. Similar improvements in physical function were observed in patients after completion of the exercise programme irrespective of exercise setting, whereas patient exercising in a municipality setting had higher positive changes in QOL than patients undergoing the same exercise programme in a hospital setting.

Decline in gross motor skills in adult Rett syndrome; results from a Danish longitudinal study.

Longevity of individuals with neurodevelopmental diseases as Rett syndrome (RTT) has increased and many reach adulthood and old age. There is therefore a need to increase knowledge about the course of RTT in adults in order to improve medical care management and quality of life. We did a longitudinal study to address if a possible decline in motor skills in adults with RTT can be explained by the presence of common medical conditions as epilepsy, breathing disturbance, and scoliosis. Data from the Danish RTT database, medical files, and videos from visits at the national Center for Rett syndrome were reviewed. The study included 24 individuals aged 30-66 years at last visit after a follow-up period of 6-12 years. Results showed a clinically observable and significant decline in gross motor skills using the Rett syndrome Gross Motor Scale (RSGMS) with a tendency of less decline in the individuals with the best motor abilities. The frequencies of comorbidities were high. Decline in RSGMS score was associated with the presence of epilepsy and severe scoliosis that had been conservatively managed. The results emphasize that epilepsy plays a significant role in the adult RTT life and management of severe scoliosis in the younger years has impact on the motor abilities in adulthood.

Exercise training is associated with reduced pains from the musculoskeletal system in patients with type 2 diabetes.

AIMS: To investigate the effect of exercise training on musculoskeletal pain in patients with type 2 diabetes. METHODS: The intervention was exercise twice weekly for 12 weeks. The primary outcome was musculoskeletal pain assessed using a 0-10 Numeric Rating Scale (NRS) in 11 body sites. Secondary outcomes were use of analgesics, glycaemic control and body weight. RESULTS: The participants (n = 69) were 66 ±â€¯10 years old, 38 were men and 50 completed the intervention. Pain in the limbs was more frequently reported by the participants compared to a matched general population (80.9% vs 65.3%, p = 0.007). The participants who had any pain at baseline (NRS > 0) and severe pain (NRS > 3) reported significantly decreased pain in the feet, calf muscles, knees, thighs, hips, lower back and arms after the training period. Use of analgesics was unchanged, HbA1c (mmol/mol) decreased from 60 ±â€¯15 to 54 ±â€¯11, p < 0.001 and body weight (kg) decreased from 100.5 ±â€¯19.1 to 98.6 ±â€¯17.7, p = 0.005. CONCLUSIONS: The participants with type 2 diabetes reported more frequent pain than a matched general population. The training intervention was associated with reduced musculoskeletal pain. Reduced pain may together with a positive impact on glycaemic control be an important motivational factor in patients with type 2 diabetes to perform exercise training.

Facilitators and Barriers of Participation in "Uptime" Activities in Girls and Women With Rett Syndrome: Perspectives From Parents and Professionals.

Rett syndrome (RTT) is a rare neurodevelopmental disorder usually affecting females. It is associated with intellectual and multiple disabilities leading to a high level of dependency in all aspects of daily living including participation in physical activities. This study explored facilitators and barriers to "uptime" (non-sedentary) activities in Danish girls and women with RTT as perceived by parents and professionals using focus groups. Through thematic analysis, one central theme emerged: a constant balance to do the best thing for the girl or woman. Within the central theme, five subthemes of facilitators and barriers were identified relating to the individual and the physical, organizational, social, and attitudinal environments. Environmental barriers can be reduced through policy and management-level changes in health promotion and strong advocacy of physical activity by health professionals. Targeting both facilitators and barriers of "uptime" activities enables the planning and implementing of health-promoting interventions in individuals with RTT.

Functional abilities in aging women with Rett syndrome - the Danish cohort.

Rett syndrome (RTT) is a neurodevelopmental disorder, which mainly affects females and results in multiple disabilities. Many clinical descriptions of the symptoms and functional abilities have been made medically, though mainly in children with RTT. Previous reports have established that even though the syndrome causes severe psychomotor disability, women with RTT can live long into adulthood. PURPOSE: We aim to describe what to expect from aging women with RTT regarding some of the basic functional abilities that are used in daily activities and that could have an impact on quality of life in these women. METHODS: A team of two medical doctors, a physiotherapist and an educational psychological adviser, performed clinical evaluations of 27 women with RTT in Denmark above 30 years of age and confirmed MECP2 mutation. RESULTS: We found that 63% of the women were able to walk outside their homes and only 11% were not able to walk at all. However, 67% could not transfer from sitting to standing position without support. There was profound difficulties communicating, but 85.1% of the women could either consistently point with their hand or eyes to things of their interest. CONCLUSIONS: Women with RTT are very dependent on caregivers who maintain and rehabilitate their functional abilities. They can often walk short distances unassisted, but do have trouble transferring and thus getting up from a chair on their own. They have severe problems communicating and they often perform subtle signs that can be difficult to recognize. Implications for rehabilitation 3/4 of aging RTT women are household ambulators - daily training of motor functions and focus on assisting the initiation of movements are needed lifelong to maintain walking ability and participation in daily activities More than half of aging women with RTT can grab on to things - persons with hand function should be motivated to use this ability in the context of eating Communication is a difficult task especially for the aging RTT women - Communicative signs, their meaning and how to react to them should be written down for every woman in an easy accessible way to all caregivers The majority of aging RTT women can point out things of interest - they should be given the opportunity to participate in choice making.

Evidence for aggregation of protein kinase CK2 in the cell: a novel strategy for studying CK2 holoenzyme interaction by BRET(2).

Protein kinase CK2 is a ubiquitous pro-survival kinase whose substrate targets are involved in various cellular processes. Crystal structure analysis confirmed constitutive activity of the kinase, yet CK2 activity regulation in the cell is still obscure. In-vitro studies suggest autoinhibitory aggregation of the hetero-tetrameric CK2 holoenzyme as a basis for CK2 regulation. In this study, we applied bioluminescent resonance energy transfer (BRET) technology to investigate CK2 holoenzyme aggregation in living cells. We designed a BRET(2) pair consisting of the fusion proteins CK2α-Rluc8 and CK2α-GFP(2). This BRET(2) sensor reported specific interaction of CK2 holoenzyme complexes. Furthermore, the BRET(2) sensor was applied to study modulators of CK2 aggregation. We found that CK2 aggregation is not static and can be influenced by the CK2-binding protein alpha subunit of the heterotrimeric G-protein that stimulates adenylyl cyclase (Gαs) and the polycationic compound polylysine. Gαs, but not the CK2 substrate ß-arrestin2, decreased the BRET(2) signal by up to 50%. Likewise polylysine, but not the CK2 inhibitor DRB, decreased the signal in a dose-dependent manner up to 50%. For the first time, we present direct experimental evidence for CK2 holoenzyme aggregates in the cell. Our data suggest that CK2 activity may be controlled by holoenzyme aggregation, to our knowledge a novel mechanism for protein kinase regulation. Moreover, the BRET(2) sensor used in our study is a novel tool for studying CK2 regulation by aggregation and pharmacological screening for novel allosteric CK2 effectors.

Mathematical models for quantitative assessment of bioluminescence resonance energy transfer: application to seven transmembrane receptors oligomerization.

The idea that seven transmembrane receptors (7TMRs; also designated G-protein coupled receptors, GPCRs) might form dimers or higher order oligomeric complexes was formulated more than 20 years ago and has been intensively studied since then. In the last decade, bioluminescence resonance energy transfer (BRET) has been one of the most frequently used biophysical methods for studying 7TMRs oligomerization. This technique enables monitoring physical interactions between protein partners in living cells fused to donor and acceptor moieties. It relies on non-radiative transfer of energy between donor and acceptor, depending on their intermolecular distance (1-10 nm) and relative orientation. Results derived from BRET-based techniques are very persuasive; however, they need appropriate controls and critical interpretation. To overcome concerns about the specificity of BRET-derived results, a set of experiments has been proposed, including negative control with a non-interacting receptor or protein, BRET dilution, saturation, and competition assays. This article presents the theoretical background behind BRET assays, then outlines mathematical models for quantitative interpretation of BRET saturation and competition assay results, gives examples of their utilization and discusses the possibilities of quantitative analysis of data generated with other RET-based techniques.

Extending the light-harvesting properties of transition-metal dendrimers.

We report a study of the electronic energy-transfer dynamics within the transition-metal polypyridine complex OsRu3pyr6 (Os[(dpp)Ru(bpy{pyrene})2]3(8+), where dpp=2,3-bis(2'-pyridyl)pyrazine and bpy=2,2'-bipyridine) after excitation with UV light. By using a broadband visible femtosecond probe, we are able to simultaneously detect both the energy transfer from the peripheral aromatic ligands to the Os center and the sub-picosecond energy transfer from the initially excited Ru-bpy ligand-centered state to the Os triplet metal-to-ligand charge-transfer (MLCT) state. Pyrene energy transfer occurs from both the nonrelaxed and the relaxed S(1) states on timescales of 6 and 45 ps, respectively. In both cases, the energy transfer is described by means of Förster energy transfer theory. Sub-picosecond energy transfer within the OsRu3 metal-ligand core most likely includes a direct energy transfer between the higher-lying ligand-centered states on Ru and Os, in addition to the transfer between the MLCT states. The absorption cross-sections in both the UV and the visible spectral regions are enhanced by attaching the aromatic pyrene ligands. Furthermore, energy transfer is directed only towards the Os core, which ultimately leads to an exclusive population of the Os-based triplet MLCT state, thus making the OsRu3pyr6 transition metal-polypyridine dendrimer an obvious candidate for artificial light-harvesting systems.

Structural induced control of energy transfer within Zn(II)-porphyrin dendrimers.

We report on a study of singlet-singlet annihilation kinetics in a series of Zn(II)-porphyrin-appended dendrimers, where the energy transfer efficiency is significantly improved by extending the molecular chain that connects the light-harvesting chromophores to the dendrimeric backbone with one additional carbon. For the largest dendrimer having 64 Zn(II)-porphyrins, only approximately 10% of the excitation intensity is needed in order to observe the same extent of annihilation in the dendrimers with the additional carbon in the connecting chain as compared to those without. Complete annihilation, until only one chromophore remains excited, now occurs within subunits of seven chromophores, when half of the chromophores are excited. The improvement of the annihilation efficiency in the largest dendrimer with 64 porphyrins can be explained by the presence of a the two-step delayed annihilation process, involving energy hopping from excited to nonexcited chromophores prior to annihilation. In the smallest dendrimer with only four chromophores, delayed annihilation is not present, since the direct annihilation process is more efficient than the two-step delayed annihilation process. As the dendrimer size increases and the chances of originally exciting two neighboring chromophores decreases, the delayed annihilation process becomes more visible. The additional carbon, added to the connecting chain, results in more favorable chromophore distances and orientations for energy hopping. Hence, the improved energy transfer properties makes the Zn(II)-porphyrin-appended dendrimers with the additional carbon promising candidates as light-harvesting antennas for artificial photosynthesis.

Energy transfer within Zn-porphyrin dendrimers: study of the singlet-singlet annihilation kinetics.

In this article, we explore energy transfer processes within a series of Zn-porphyrin-appended dendrimers by means of excitation intensity dependent transient absorption measurements. We report singlet-singlet annihilation on two distinct time scales of 18 +/- 5 ps and 130 +/- 10 ps in the dimer and the dendrimers. The two distinct processes reflect the presence of two structural conformer distributions. Analysis of the singlet-singlet annihilation transient kinetics shows that sequential annihilation occurs within subunits up to four Zn-porphyrins in the dendrimers. The onset of the singlet-singlet annihilation process depending on the size of the molecule reveals a difference in the number of communicating Zn-porphyrins. We further report a full characterization of the transient absorption kinetics of the monomer over a spectral range from 450 to 730 nm.

The primary photodynamics of aqueous nitrate: formation of peroxynitrite.

We have examined the photochemical reactions occurring after irradiation at 200 nm of the aqueous nitrate ion, NO3(-)(aq). Using femtosecond transient absorption spectroscopy over the range 194-388 nm, we have characterized the formation and subsequent relaxation of the primary photoproducts of nitrate photolysis. The dominant photoproduct is the cis-isomer of peroxynitrite, which accounts for 48% of the excited state molecules initially produced. A slightly smaller fraction, 44%, of the excited molecules return to the electronic ground state of NO3(-) and relax to the vibrational ground state in 2 ps. The remaining 8% of the molecules initially excited react via the *NO + *O2(-) or the NO- + O2 dissociation channels. Formation of NO2(-) and *NO2 is not observed, suggesting that the previous observations of these species in steady-state photolysis are caused by reactions occurring on a longer time scale.