Lack, Justin*
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BACKGROUND: Cardiorespiratory fitness (CRF) is an important indicator of current and future health. While the impact of habitual physical activity on CRF is well established, the role of sedentary behaviour (SB) remains less understood. OBJECTIVE: We aimed to determine the effect of SB on CRF. METHODS: Searches were conducted in MEDLINE, Embase, PsycINFO, CINAHL and SPORTDiscus from inception to August 2022. Randomised controlled trials, quasi-experimental studies and cohort studies that assessed the relationship between SB and CRF were eligible. Narrative syntheses and meta-analyses summarised the evidence, and Grading of Recommendations, Assessment, Development and Evaluation (GRADE) certainty was based on evidence from randomised controlled trials. RESULTS: This review included 18 studies that focused on youth (four randomised controlled trials, three quasi-experimental studies, 11 cohort studies) and 24 on adult populations (15 randomised controlled trials, five quasi-experimental studies, four cohort studies). In youth and adults, evidence from randomised controlled trials suggests mixed effects of SB on CRF, but with the potential for interventions to improve CRF. Quasi-experimental and cohort studies also support similar conclusions. Certainty of evidence was very low for both age groups. A meta-analysis of adult randomised controlled trials found that interventions targeting reducing SB, or increasing physical activity and reducing SB, had a significant effect on post-peak oxygen consumption (mean difference = 3.16 mL.kg-1.min-1, 95% confidence interval: 1.76, 4.57). CONCLUSIONS: Evidence from randomised controlled trials indicates mixed associations between SB and CRF, with the potential for SB to influence CRF, as supported by meta-analytical findings. Further well-designed trials are warranted to confirm the relationship between SB and CRF, explore the effects of SB independent from higher intensity activity, and investigate the existence of such relationships in paediatric populations. CLINICAL TRIAL REGISTRATION: PROSPERO CRD42022356218.
Based on light and scanning electron microscopical studies, two new species of Hysterothylacium Ward & Magath, 1917 (Nematoda: Anisakidae) are described from the digestive tract of perciform fishes off New Caledonia: H. alatum n. sp. from Plectropomus laevis (Lacépède) (Serranidae) and H. sphyraenae n. sp. from Sphyraena qenie Klunzinger (Sphyraenidae). The former species (H. alatum) is mainly characterised by its large body (male 42.05 mm, gravid females 51.18-87.38 mm long), the shape of the dorsal lip, conspicuously broad cervical alae, a short caecum and a long ventricular appendix, the length of the spicules (925 µm), the number (25 pairs) and distribution of the genital papillae and the tail tip bearing numerous minute cuticular protuberances. The other species (H. sphyraenae) is mainly characterised by the presence of narrow lateral alae, a short caecum and a long ventricular appendix, the length (762-830 µm) and shape of the spicules, the number (37-38 pairs) and arrangement of the genital papillae, and by the tail tip which lacks any distinct cuticular projections visible under the light microscope. In addition, and unidentifiable at the species level, conspicuously large (45.71-66.10 mm long) larvae of Contracaecum Railliet & Henry, 1912, were found in the body cavity of P. laevis, which serves as a paratenic host for this parasite.
- MeSH
- Ascaridoidea anatomie a histologie klasifikace fyziologie ultrastruktura MeSH
- druhová specificita MeSH
- gastrointestinální trakt parazitologie MeSH
- interakce hostitele a parazita MeSH
- larva MeSH
- mikroskopie elektronová rastrovací MeSH
- Percoidea parazitologie MeSH
- ryby parazitologie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Geografické názvy
- Nová Kaledonie MeSH
Clinical applications of precision oncology require accurate tests that can distinguish true cancer-specific mutations from errors introduced at each step of next-generation sequencing (NGS). To date, no bulk sequencing study has addressed the effects of cross-site reproducibility, nor the biological, technical and computational factors that influence variant identification. Here we report a systematic interrogation of somatic mutations in paired tumor-normal cell lines to identify factors affecting detection reproducibility and accuracy at six different centers. Using whole-genome sequencing (WGS) and whole-exome sequencing (WES), we evaluated the reproducibility of different sample types with varying input amount and tumor purity, and multiple library construction protocols, followed by processing with nine bioinformatics pipelines. We found that read coverage and callers affected both WGS and WES reproducibility, but WES performance was influenced by insert fragment size, genomic copy content and the global imbalance score (GIV; G > T/C > A). Finally, taking into account library preparation protocol, tumor content, read coverage and bioinformatics processes concomitantly, we recommend actionable practices to improve the reproducibility and accuracy of NGS experiments for cancer mutation detection.
- MeSH
- benchmarking * MeSH
- buněčné linie MeSH
- lidé MeSH
- mutace MeSH
- nádorové buněčné linie MeSH
- nádory genetika patologie MeSH
- reprodukovatelnost výsledků MeSH
- sekvenční analýza DNA normy MeSH
- sekvenování celého genomu normy MeSH
- sekvenování exomu normy MeSH
- vysoce účinné nukleotidové sekvenování metody MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
The emerging use of qPCR and dPCR in regulated bioanalysis and absence of regulatory guidance on assay validations for these platforms has resulted in discussions on lack of harmonization on assay design and appropriate acceptance criteria for these assays. Both qPCR and dPCR are extensively used to answer bioanalytical questions for novel modalities such as cell and gene therapies. Following cross-industry conversations on the lack of information and guidelines for these assays, an American Association of Pharmaceutical Scientists working group was formed to address these gaps by bringing together 37 industry experts from 24 organizations to discuss best practices to gain a better understanding in the industry and facilitate filings to health authorities. Herein, this team provides considerations on assay design, development, and validation testing for PCR assays that are used in cell and gene therapies including (1) biodistribution; (2) transgene expression; (3) viral shedding; (4) and persistence or cellular kinetics of cell therapies.
BACKGROUND: Whole-genome sequencing (WGS) of Treponema pallidum subspecies pallidum (TPA) has been constrained by the lack of in vitro cultivation methods for isolating spirochetes from patient samples. METHODS: We built upon recently developed enrichment methods to sequence TPA directly from primary syphilis chancre swabs collected in Guangzhou, China. RESULTS: By combining parallel, pooled whole-genome amplification with hybrid selection, we generated high-quality genomes from 4 of 8 chancre-swab samples and 2 of 2 rabbit-passaged isolates, all subjected to challenging storage conditions. CONCLUSIONS: This approach enabled the first WGS of Chinese samples without rabbit passage and provided insights into TPA genetic diversity in China.
- MeSH
- králíci MeSH
- lidé MeSH
- sekvenování celého genomu MeSH
- syfilis * diagnóza mikrobiologie MeSH
- Treponema pallidum klasifikace genetika MeSH
- tvrdý vřed * diagnóza mikrobiologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
- Geografické názvy
- Čína MeSH
Mast cell leukemia (MCL) is a rare subtype of systemic mastocytosis defined by ≥20% mast cells (MC) on a bone marrow aspirate. We evaluated 92 patients with MCL from the European Competence Network on Mastocytosis registry. Thirty-one (34%) patients had a diagnosis of MCL with an associated hematologic neoplasm (MCL-AHN). Chronic MCL (lack of C-findings) comprised 14% of patients, and only 4.5% had "leukemic MCL" (≥10% circulating MCs). KIT D816V was found in 62/85 (73%) evaluable patients; 9 (11%) individuals exhibited alternative KIT mutations, and no KIT variants were detected in 14 (17%) subjects. Ten evaluable patients (17%) had an abnormal karyotype and the poor-risk SRSF2, ASXL1, and RUNX1 (S/A/R) mutations were identified in 16/36 (44%) patients who underwent next-generation sequencing. Midostaurin was the most common therapy administered to 65% of patients and 45% as first-line therapy. The median overall survival (OS) was 1.6 years. In multivariate analysis (S/A/R mutations excluded owing to low event rates), a diagnosis of MCL-AHN (hazard ratio [HR], 4.7; 95% confidence interval [CI], 1.7-13.0; P = .001) and abnormal karyotype (HR, 5.6; 95% CI, 1.4-13.3; P = .02) were associated with inferior OS; KIT D816V positivity (HR, 0.33; 95% CI, 0.11-0.98; P = .04) and midostaurin treatment (HR, 0.32; 95% CI, 0.08-0.72; P = .008) were associated with superior OS. These data provide the most comprehensive snapshot of the clinicopathologic, molecular, and treatment landscape of MCL to date, and should help further inform subtyping and prognostication of MCL.
Mammals and birds have a specialized cardiac atrioventricular conduction system enabling rapid activation of both ventricles. This system may have evolved together with high heart rates to support their endothermic state (warm-bloodedness) and is seemingly lacking in ectothermic vertebrates from which first mammals then birds independently evolved. Here, we studied the conduction system in crocodiles (Alligator mississippiensis), the only ectothermic vertebrates with a full ventricular septum. We identified homologues of mammalian conduction system markers (Tbx3-Tbx5, Scn5a, Gja5, Nppa-Nppb) and show the presence of a functional atrioventricular bundle. The ventricular Purkinje network, however, was absent and slow ventricular conduction relied on trabecular myocardium, as it does in other ectothermic vertebrates. We propose the evolution of the atrioventricular bundle followed full ventricular septum formation prior to the development of high heart rates and endothermy. In contrast, the evolution of the ventricular Purkinje network is strongly associated with high heart rates and endothermy.
- MeSH
- aligátoři a krokodýli embryologie genetika fyziologie MeSH
- embryo nesavčí metabolismus MeSH
- Hisův svazek embryologie metabolismus fyziologie MeSH
- hybridizace in situ MeSH
- mezikomorová přepážka embryologie metabolismus fyziologie MeSH
- modely kardiovaskulární MeSH
- převodní systém srdeční embryologie fyziologie MeSH
- proteiny T-boxu genetika metabolismus MeSH
- Purkyňova vlákna embryologie metabolismus fyziologie MeSH
- srdce embryologie fyziologie MeSH
- srdeční frekvence genetika fyziologie MeSH
- srdeční komory embryologie metabolismus MeSH
- vývojová regulace genové exprese MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Objective Real-life management of patients with hypertension and chronic kidney disease (CKD) among European Society of Hypertension Excellence Centres (ESH-ECs) is unclear : we aimed to investigate it. Methods A survey was conducted in 2023. The questionnaire contained 64 questions asking ESH-ECs representatives to estimate how patients with CKD are managed. Results Overall, 88 ESH-ECS representatives from 27 countries participated. According to the responders, renin-angiotensin system (RAS) blockers, calcium-channel blockers and thiazides were often added when these medications were lacking in CKD patients, but physicians were more prone to initiate RAS blockers (90% [interquartile range: 70-95%]) than MRA (20% [10-30%]), SGLT2i (30% [20-50%]) or (GLP1-RA (10% [5-15%]). Despite treatment optimisation, 30% of responders indicated that hypertension remained uncontrolled (30% (15-40%) vs 18% [10%-25%]) in CKD and CKD patients, respectively). Hyperkalemia was the most frequent barrier to initiate RAS blockers, and dosage reduction was considered in 45% of responders when kalaemia was 5.5-5.9 mmol/L. Conclusions RAS blockers are initiated in most ESH-ECS in CKD patients, but MRA and SGLT2i initiations are less frequent. Hyperkalemia was the main barrier for initiation or adequate dosing of RAS blockade, and RAS blockers' dosage reduction was the usual management.
- MeSH
- antagonisté receptorů pro angiotenzin terapeutické užití MeSH
- antihypertenziva terapeutické užití MeSH
- blokátory kalciových kanálů terapeutické užití MeSH
- chronická renální insuficience * komplikace farmakoterapie MeSH
- hypertenze * farmakoterapie MeSH
- lidé středního věku MeSH
- lidé MeSH
- průzkumy a dotazníky MeSH
- společnosti lékařské MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- multicentrická studie MeSH
- Geografické názvy
- Evropa MeSH
Závěrečná zpráva o řešení grantu Agentury pro zdravotnický výzkum MZ ČR
Nestr.
Tento výzkumný projekt je zaměřen na zásadní problematiku léčby pacientů s metastatickými nádory prsu, u nichž chybí efektivní léčebná strategie v případě návratu nemoci po ukončení konvenční chemo-endokrinní terapie. Zde navrhujeme využít v nové roli lék disufiram (DSF) u těchto pacientů. DSF se používá již více než 60let jako anti-atraktant při léčbě alkoholové závislosti. V těle se metabolizuje na dithiokarbamát – biologicky aktivní látku u níž četné studie prokázaly schopnost interference s buněčnými drahami hrající důležitou roli pro přežívání nádorových buněk. V návaznosti na dokumentované případy regrese pokročilých nádorových onemocnění u uživatelů DSF, epidemiologická data, reportované placebo-kontrolované klinické studie, studie na buněčných liniích a xenograftech včetně nových dat o molekulárním působení DSF získaných z naší laboratoře jsme přesvědčeni, že existuje dostatečné množství důkazů opravňující zahájení námi navrhovaného projektu.; This research project addresses a fundamental problem in the treatment of patients with metastatic breast cancer (MBC) cancer: a severe lack of effective systemic treatment options following disease recurrence after conventional chemo-endocrine therapy. Here, we propose to assess a repurposing strategy by introducing the drug disulfiram (Antabus) to patients with MBC. Disulfiram was invented in Denmark and has been used globally as an anti-alcoholic drug for over 60 years. In the body, one molecule of disulfiram is cleaved to two molecules of dithiocarb - the active substance which was shown in multiple studies capable of interfering with multiple cancer pro-survival pathways. Based on case reports evidence, epidemiologic data, placebo-controlled trials, xenograft and cell-culture based experiments including new mechanistic data generated in our laboratory we strongly believe there is sufficient preliminary evidence to justify the project that we propose here
- MeSH
- chemorezistence MeSH
- disulfiram terapeutické užití MeSH
- ethylenbis(dithiokarbamáty) terapeutické užití MeSH
- lidé MeSH
- metastázy nádorů farmakoterapie MeSH
- nádory prsu farmakoterapie MeSH
- protinádorové látky terapeutické užití MeSH
- recidiva MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Konspekt
- Farmacie. Farmakologie
- NLK Obory
- farmacie a farmakologie
- farmakoterapie
- onkologie
- NLK Publikační typ
- závěrečné zprávy o řešení grantu AZV MZ ČR
Modern society, particularly its rapid and persistent information and communication technologies development aiming at facilitating the life of individuals, technically speaking did reduce distances and it did make life friendlier. At the same time, probably unwillingly or unwittingly, it has estranged the human from vital life contents. Therefore, the question is whether life quality has indeed improved. A wide and substantial definition of life quality is required as to allow everybody, regardless of their social environment, status, psychic and physical state, to find grounds for its improvement. Prosperity is related to feelings and emotions that are important for everybody’s life, yet they do not represent the same degree of satisfaction for everybody. Health in its basic definition, namely as balance in psychic, physical and social area and not merely as absence of disease, has undoubtedly a particular significance and role as a life quality factor. Subjective evaluation of our own health state and quality of our life reflects the balance between our needs and possibilities offered by social environment. Movement and sports are a humans’ crucial health source. Due to increasing use of topmost technologies motor activity has been decreasing, in the most developed parts of the world it has even been disappearing. The active population proportion engaged in sedentary jobs has never been so large moreover they are engaged in sedentary spare time activities, mostly at a television or a computer. Lack of a sufficient motor and/or sports (motor/ sports) activity is strongly associated with chronic non-contagious diseases that are today among the major mortality factors. Adequate state policy places at the centre of its interest its citizens and their needs and desires. In its managment it follows the principles of economy, therefore it cannot and must not neglect the health protection and enhancement of individuals, families and the whole population as the basis of a quality and productive life, as well as of a general social prosperity. An important factor in health enhancement, regaining and preserving is undoubtedly movement and sports. Thus, motor/ sports activity ought to become a part of everybody’s daily routines. It models and triggers behaviour intentions with a clear operationalized objective: to be active – to be in good health – to live a quality life – in a spiral model of individual’s development. Absence of motor/sports activity in the life of children and youth means more than just a threat to their health, it is a threat to their creativity, knowledge and success.
