Motor skill interventions can improve the motor proficiency of children with autism, however, the secondary effects associated with these interventions are not well understood. The aim of this study is to describe 1) parents' experiences with an early motor skill intervention for their children with autism, and 2) the secondary effects of the intervention on parents and families. Parents (n = 8) of four-year-old children with autism who participated in a 12-week motor skill intervention were invited to take part in a semi-structured interview to discuss their experiences. The study was grounded in descriptive phenomenology. Three themes emerged from the data. Theme 1: Parent Attendance - observing the motor skill intervention was essential in order for parents to benefit from the experience themselves (e.g., socializing with the other parents), Theme 2: Eye-Opening Experience - the intervention shed light on the children's capabilities and the importance of motor skill development, Theme 3: Positive Experience - parents expressed a desire for more opportunities like this within the community. These findings indicate that early motor skill interventions for children with autism can also benefit parents and families. In order to better meet the needs of families of children with autism, clinicians should educate parents on the importance of motor skill development early, and highlight opportunities for active engagement at home and in the community.

• MeSH
• autistická porucha * rehabilitace   MeSH
• lidé MeSH
• motorické dovednosti MeSH
• pohybová aktivita MeSH
• postižené děti MeSH
• předškolní dítě MeSH
• raná péče metody   MeSH
• rodiče * MeSH
• rodina MeSH
• rozhovory jako téma MeSH
• Check Tag
• lidé MeSH
• předškolní dítě MeSH

• Klíčová slova
• lékařství vnitřní - nemoci - klasifikace - učebnice, lékařství preventivní - diagnostika - učebnice, systémy terapeutické - lékařství vnitřní - učebnice,

• Konspekt
• Patologie. Klinická medicína
• NLK Obory
• vnitřní lékařství
• chemie, klinická chemie

• MeSH
• antibiotická rezistence MeSH
• Escherichia coli účinky léků   MeSH
• fenotyp MeSH
• klonování DNA MeSH
• plazmidy MeSH
• telur MeSH

When individuals breed more than once, parents are faced with the choice of whether to re-mate with their old partner or divorce and select a new mate. Evolutionary theory predicts that, following successful reproduction with a given partner, that partner should be retained for future reproduction. However, recent work in a polygamous bird, has instead indicated that successful parents divorced more often than failed breeders (Halimubieke et al. in Ecol Evol 9:10734-10745, 2019), because one parent can benefit by mating with a new partner and reproducing shortly after divorce. Here we investigate whether successful breeding predicts divorce using data from 14 well-monitored populations of plovers (Charadrius spp.). We show that successful nesting leads to divorce, whereas nest failure leads to retention of the mate for follow-up breeding. Plovers that divorced their partners and simultaneously deserted their broods produced more offspring within a season than parents that retained their mate. Our work provides a counterpoint to theoretical expectations that divorce is triggered by low reproductive success, and supports adaptive explanations of divorce as a strategy to improve individual reproductive success. In addition, we show that temperature may modulate these costs and benefits, and contribute to dynamic variation in patterns of divorce across plover breeding systems.

• MeSH
• biologická evoluce * MeSH
• Charadriiformes fyziologie   MeSH
• chov MeSH
• párová vazba MeSH
• rozmnožování fyziologie   MeSH
• rozvod MeSH
• sexuální chování zvířat fyziologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

• MeSH
• bezdrátová technologie MeSH
• bradykardie * terapie   MeSH
• defibrilátory implantabilní * škodlivé účinky   MeSH
• design vybavení MeSH
• kardiostimulace umělá škodlivé účinky   metody   MeSH
• kardiostimulátor * škodlivé účinky   MeSH
• lidé středního věku MeSH
• lidé MeSH
• náhlá srdeční smrt * prevence a kontrola   etiologie   MeSH
• následné studie MeSH
• senioři MeSH
• srdeční arytmie * komplikace   terapie   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• klinické zkoušky MeSH
• multicentrická studie MeSH

• MeSH
• alely MeSH
• CRISPR-Cas systémy * MeSH
• editace genu MeSH
• myši MeSH
• protein Cas9 * metabolismus   MeSH
• reprodukovatelnost výsledků MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• dopisy MeSH
• komentáře MeSH

BACKGROUND: CRISPR-Cas9 gene-editing technology has facilitated the generation of knockout mice, providing an alternative to cumbersome and time-consuming traditional embryonic stem cell-based methods. An earlier study reported up to 16% efficiency in generating conditional knockout (cKO or floxed) alleles by microinjection of 2 single guide RNAs (sgRNA) and 2 single-stranded oligonucleotides as donors (referred herein as "two-donor floxing" method). RESULTS: We re-evaluate the two-donor method from a consortium of 20 laboratories across the world. The dataset constitutes 56 genetic loci, 17,887 zygotes, and 1718 live-born mice, of which only 15 (0.87%) mice contain cKO alleles. We subject the dataset to statistical analyses and a machine learning algorithm, which reveals that none of the factors analyzed was predictive for the success of this method. We test some of the newer methods that use one-donor DNA on 18 loci for which the two-donor approach failed to produce cKO alleles. We find that the one-donor methods are 10- to 20-fold more efficient than the two-donor approach. CONCLUSION: We propose that the two-donor method lacks efficiency because it relies on two simultaneous recombination events in cis, an outcome that is dwarfed by pervasive accompanying undesired editing events. The methods that use one-donor DNA are fairly efficient as they rely on only one recombination event, and the probability of correct insertion of the donor cassette without unanticipated mutational events is much higher. Therefore, one-donor methods offer higher efficiencies for the routine generation of cKO animal models.

• MeSH
• alely * MeSH
• blastocysta metabolismus   MeSH
• CRISPR-Cas systémy genetika   MeSH
• faktorová analýza statistická MeSH
• mikroinjekce MeSH
• myši knockoutované MeSH
• protein 2 vázající methyl-CpG genetika   metabolismus   MeSH
• protein Cas9 metabolismus   MeSH
• regresní analýza MeSH
• reprodukovatelnost výsledků MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery.

• MeSH
• esenciální geny MeSH
• genetické asociační studie metody   MeSH
• genomika MeSH
• lidé MeSH
• myši knockoutované MeSH
• myši MeSH
• nemoc genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• hodnotící studie MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH

Chronic fatigue syndrome/myalgic encephalomyelitis (CFS/ME) is a disabling long-term condition of unknown cause. The National Institute for Health and Care Excellence (NICE) published a guideline in 2021 that highlighted the seriousness of the condition, but also recommended that graded exercise therapy (GET) should not be used and cognitive-behavioural therapy should only be used to manage symptoms and reduce distress, not to aid recovery. This U-turn in recommendations from the previous 2007 guideline is controversial.We suggest that the controversy stems from anomalies in both processing and interpretation of the evidence by the NICE committee. The committee: (1) created a new definition of CFS/ME, which 'downgraded' the certainty of trial evidence; (2) omitted data from standard trial end points used to assess efficacy; (3) discounted trial data when assessing treatment harm in favour of lower quality surveys and qualitative studies; (4) minimised the importance of fatigue as an outcome; (5) did not use accepted practices to synthesise trial evidence adequately using GRADE (Grading of Recommendations, Assessment, Development and Evaluations trial evidence); (6) interpreted GET as mandating fixed increments of change when trials defined it as collaborative, negotiated and symptom dependent; (7) deviated from NICE recommendations of rehabilitation for related conditions, such as chronic primary pain and (8) recommended an energy management approach in the absence of supportive research evidence.We conclude that the dissonance between this and the previous guideline was the result of deviating from usual scientific standards of the NICE process. The consequences of this are that patients may be denied helpful treatments and therefore risk persistent ill health and disability.

• MeSH
• kognitivně behaviorální terapie * MeSH
• lidé MeSH
• průzkumy a dotazníky MeSH
• syndrom chronické únavy * diagnóza   terapie   MeSH
• terapie cvičením MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

• MeSH
• delece genu * MeSH
• fenotyp MeSH
• genetické asociační studie * MeSH
• genom * MeSH
• genotyp * MeSH
• internet MeSH
• mezinárodní spolupráce MeSH
• mutageneze MeSH
• myší embryonální kmenové buňky cytologie   metabolismus   MeSH
• myši knockoutované MeSH
• myši MeSH
• šíření informací MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH