The aim of the present study was to examine gender and age-specific effects on subjective daytime sleepiness (as measured by the Epworth Sleepiness Scale), body weight and eating behaviour in patients with central disorders of hypersomnolence. Based on the European Narcolepsy Network database, we compared 1035 patients with narcolepsy type I and 505 patients with other central disorders of hypersomnolence ("narcoleptic borderland"), including narcolepsy type II (N = 308) and idiopathic hypersomnia (N = 174), using logistic regression and general linear models. In the entire study population, the Epworth Sleepiness Scale was higher in women (N = 735, mean age = 30 years, mean Epworth Sleepiness Scale = 16.6 ± SD 3.9) than in men (N = 805, mean age = 32 years, mean Epworth Sleepiness Scale = 15.8 ± SD 4.4). In women with narcolepsy type I (N = 475), both Epworth Sleepiness Scale and body mass index increased in parallel with age. In women of the narcoleptic borderland (N = 260), the Epworth Sleepiness Scale markedly peaked in their early 30s, while body mass index only started to rise at that age. This rise in body mass index following the Epworth Sleepiness Scale peak cannot be explained by sleepiness-induced uncontrolled eating, as self-reported uncontrolled eating was negatively associated with the Epworth Sleepiness Scale in this group. We propose that the narcoleptic borderland harbours a unique cluster of women in their fertile years with an unexplored aetiology requiring further investigation towards tailored interventions.
- MeSH
- Adult MeSH
- Body Mass Index * MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Narcolepsy * physiopathology MeSH
- Disorders of Excessive Somnolence * physiopathology epidemiology MeSH
- Sex Factors MeSH
- Feeding Behavior MeSH
- Body Weight MeSH
- Age Factors MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
S incidencí 1 % všech mimoděložních těhotenství se cervikální mimoděložní těhotenství (CEP – cervical ectopic pregnancy) v důsledku možné časné chybné diagnózy nebo krvácení a ruptury může stát život ohrožujícím stavem vyžadujícím neodkladnou hysterektomii, což bylo donedávna v klinické praxi pozorováno. Prezentujeme případ časně diagnostikované invazivní CEP léčené kombinovaným minimálně invazivním postupem (MIP – minimally invasive procedure) pro akutní pánevní bolest a krvácení. V našem případě jsme několik z těchto metod aplikovali na primigravidu s časnou invazivní CEP se zachováním fertility. Kombinací popsaných lokálních léků s uterotoniky a anemizací děložního hrdla, nitrožilním podáním kyseliny tranexamové a MIP se nám podařilo zachovat dělohu s minimální krevní ztrátou a možností budoucího početí.
With an incidence of 1% of all ectopic pregnancies, cervical ectopic pregnancy (CEP) is due to possible early misdiagnosis or bleeding and rupture can become a life-threatening condition with the need for urgent hysterectomy, which has been seen in clinical practice recently. We present a case of early diagnosed invasive CEP treated with combined minimally invasive procedure (MIP) due to acute pelvic pain and bleeding. In our case, we applied several of these methods to a primigravida with early invasive CEP with fertility preservation. By combining the self-described local medications with uterotonics and cervical anaemia treatment, intravenous tranexamic acid and MIP, we were able to preserve the uterus with minimal blood loss and the possibility of future conception.
- MeSH
- Early Diagnosis MeSH
- Adult MeSH
- Humans MeSH
- Pregnancy, Ectopic * diagnostic imaging therapy MeSH
- Minimally Invasive Surgical Procedures methods MeSH
- Obstetric Surgical Procedures * methods MeSH
- Pregnancy MeSH
- Ultrasonography, Doppler MeSH
- Fertility Preservation MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Case Reports MeSH
This study describes the primary and secondary infertility in patients attending fertility clinics and reports factors associated with primary infertility. A cross-sectional survey was conducted in two fertility clinics in Abu Dhabi Emirate, United Arab Emirates (UAE) between December 2020 and May 2021. The collected information covered sociodemographic, lifestyle, medical, and fertility-related characteristics. The mean age and age at marriage (±SD) of the 928 patients were 35.7 (±6.7) and 25.2 (±6.3) years, respectively. Of the total, 72.0% were obese and overweight, 26.6% reported a consanguineous marriage, and 12.5% were smokers. Secondary infertility (62.5%) was more frequent than primary infertility (37.5%). Primary infertility was inversely associated with age (aOR, 0.94, 95% CI: 0.91-0.98) and not being overweight (aOR, 0.6, 95% CI: 0.4-0.9) while positively associated with a nationality other than Middle Eastern nationality (aOR, 1.9, 95% CI: 1.1-3.3), married for ≤5 years (aOR, 6.0, 95% CI: 3.9-9.3), in a nonconsanguineous marriage (aOR, 2.4, 95% CI: 1.5-3.9), having a respiratory disease (aOR, 2.3, 95% CI: 1.1-4.6), an increased age at puberty (aOR, 1.2, 95% CI: 1.0-1.3), and self-reported 6-<12 months (aOR, 2.4, 95% CI: 1.2-5.1) and ≥12 months (aOR, 3.4, 95% CI: 1.8-6.4) infertility. Patients with primary infertility were more likely to be diagnosed with infertility of an ovulation, tubal, or uterine origin (aOR, 3.9, 95% CI: 1.9-7.9). Secondary infertility was more common than primary infertility. Several preventable fertility-related risk factors including overweight, smoking, and diabetes were found to be common among the fertility clinic attendees.
- MeSH
- Infertility * epidemiology MeSH
- Fertility Clinics * MeSH
- Humans MeSH
- Overweight MeSH
- Cross-Sectional Studies MeSH
- Check Tag
- Humans MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- United Arab Emirates MeSH
STUDY QUESTION: Which chemotherapeutic agents and body site-specific radiation fields are dose-dependently associated with an increased risk of fertility impairment in long-term female childhood, adolescent and young adulthood (CAYA) cancer survivors? SUMMARY ANSWER: Busulfan, lower abdominal radiotherapy (RT) and total body irradiation (TBI) seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. WHAT IS KNOWN ALREADY: Several treatment-related fertility deficits, as assessed by both self-reported outcomes and hormonal markers are known to occur following treatment of CAYA cancer. However, knowledge regarding precise dose-related estimates of these treatment-related risks are scarce. STUDY DESIGN, SIZE, DURATION: The current case-control study was nested within the PanCareLIFE cohort study. In total, 1332 CAYA survivors from 8 countries, 9 institutions and 11 cohorts, participated in and contributed data to the study. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants were female 5-year CAYA cancer survivors. In total, 450 cases (fertility impaired survivors) and 882 matched controls (not fertility impaired survivors) were included. Fertility impairment was defined using both questionnaire data (primary or secondary amenorrhea; use of artificial reproductive techniques; unfulfilled wish to conceive) and hormonal data (FSH and anti-Müllerian hormone (AMH)). Multivariable logistic regression models were used to investigate the effect of (i) alkylating agent exposure, and (ii) dose categories for individual chemotherapeutic agents and for RT-exposed body sites. MAIN RESULTS AND THE ROLE OF CHANCE: A positive dose-effect relationship between cyclophosphamide equivalent dose (CED) score and fertility impairment was found, with survivors with a CED score > 7121 mg/m2 being at a significantly increased risk of fertility impairment (odds ratio (95% CI) = 2.6 (1.9-3.6) P < 0.001). Moreover, cumulative dose variables of the following treatments were significantly associated with fertility impairment: busulfan, carmustine, cyclophosphamide, melphalan, procarbazine, lower abdominal RT and TBI. Busulfan, lower abdominal RT and TBI seem to be associated with fertility impairment at any dose, whereas gonadotoxicity of melphalan and procarbazine is suggested at medium/high (>140 mg/m2) or high dose (>5600 mg/m2) therapy, respectively. LIMITATIONS, REASONS FOR CAUTION: Our study may have been subject to selection bias since data from about half of the original base cohorts were available for the current study. This could impact the generalizability of our study results. WIDER IMPLICATIONS OF THE FINDINGS: We identified survivors at high risk for fertility impairment and, consequently, for a reduced or even absent reproductive life span. Both girls and young women who are about to start anti-cancer treatment, as well as adult female survivors, should be counselled about future parenthood and referred to a reproductive specialist for fertility preservation, if desired. STUDY FUNDING/COMPETING INTEREST(S): This study has received funding from the European Union's Seventh Framework Programme for research, technological development and demonstration under grant agreement no. 602030. There are no competing interests. TRIAL REGISTRATION NUMBER: n/a.
- MeSH
- Child MeSH
- Adult MeSH
- Fertility MeSH
- Cohort Studies MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Neoplasms * drug therapy MeSH
- Cancer Survivors * MeSH
- Case-Control Studies MeSH
- Fertility Preservation * MeSH
- Check Tag
- Child MeSH
- Adult MeSH
- Humans MeSH
- Adolescent MeSH
- Young Adult MeSH
- Male MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
Cíl práce: Práce se zabývá klinickou částí výzkumu lidských embryonálních kmenových buněk (hESC). Cílem projektu je vznik somatických buněčných typů použitelných ve vývoji léčiv, regenerativní medicíně a buněčné terapii. Výhledem je umožnit cílenou terapii dosud nevyléčitelné nemoci. Pluripotentní hESC mají neomezenou kapacitu pro sebeobnovu. Této vlastnosti se využívá v terapii, kdy jsou z hESC vytvořeny chybějící nebo poškozené buňky v lidském těle. Je zájem vytvořit hESC linie v klinické kvalitě, použitelné v předklinických a klinických studiích. Metodika: Vytvoření hESC musí respektovat legislativu ČR a EU. Podmínkou bylo vypracovat informovaný souhlas obou dárců pro darovaná vyřazená embrya, která nejsou vhodná pro léčbu oplodněním in vitro dle směrnice 2004/23/ES. Centrum asistované reprodukce (CAR) FN Brno se podílí na odběru oocytů, kultivaci a kryokonzervaci embryí, komunikaci s klienty a zajišťování informovaných souhlasů dárců embryí. Byl vypracován předávací protokol a metodika předávání rozmrazených embryí s originálním číselným kódem. Před předáním embryí na spoluautorské pracoviště – Centrum buněčného a tkáňového inženýrství (CTEF) ICRC FN u sv. Anny – je provedeno jejich rozmrazení, v případě potřeby dokultivování do stadia blastocysty, a následně je proveden asistovaný hatching. Výsledky: V období leden 2018 až červenec 2020 bylo obesláno 138 vybraných vhodných klientek na dárcovství, z nichž 52 nereagovalo, 19 ukončilo a 29 prodloužilo skladování embryí. Pouze 38 klientek, tj. 27,5 %, souhlasilo s jejich využitím na přípravu hESC. Ve stejném období probíhala osobní komunikace s vhodnými klienty CAR a bylo získáno dalších 17 dárců embryí. Celkem bylo získáno 160 embryí od 55 dárkyň ve věku 26–42 let. Nejčastěji byla embrya zamrazena ve stadiu blastocysty (53 embrií – 33,1 %) a moruly (74 embrií – 46,3 %). Z 29 geneticky vyšetřených embryí je 5 euploidních (17,2 %), 2 mozaiky a 22 aneuploidních nebo s translokací či přenašečů s monogenní vadou. Závěr: Byl vypracován a Etickou komisí LF MU a FN Brno schválen informovaný souhlas, bylo vybráno a zajištěno 160 darovaných embryí. Je vypracován předávací protokol a metodika předávání. Plán předávání rozmrazených anonymizovaných embryí zahrnuje cca 5 rozmrazených blastocyst týdně s provedeným asistovaným hatchingem. Po předání embryí na CTEF probíhá izolace embryoblastu s následnou kultivací. Ustanovené buněčné linie hESC musí splnit specifikovaná kritéria bezpečnosti, stability a pluripotence. Věříme, že v souladu s plánem projektu získáme nejméně tři linie hESC v klinické kvalitě, poprvé vytvořené v ČR, respektující požadavky na léčivé přípravky Advanced Medicinal Therapy Products (AMTP).
Objective: The work deals with a clinical part of human embryonic stem cell (hESC) research. The aim of the project is the differentiation of somatic cell types, useful in drug development, regenerative medicine and cell therapy. The aim of this work is to enable targeted therapy of yet incurable diseases. The pluripotent hESCs have unlimited self-renewal capacity. This ability is used in therapy to create missing or damaged cells in the human body. It is of interest to develop clinical-grade hESC lines useful in preclinical and clinical studies. Methods: The derivation of the hESC must respect the legislation of the Czech Republic and the EU. The aim was to develop an informed consent of both donors for donated discarded embryos that are not suitable for treatment by in vitro fertilization according to Directive 2004/23/EC. The FNB‘s Center for Assisted Reproduction (CAR) participates in oocyte collection, cultivation and cryopreservation of embryos, communication with clients and ensuring the informed consent of embryo donors. A transport protocol and a methodology for handing over the thawed embryos with the original numerical code were developed. Before the embryos are handed over to the ICRC co-author‘s workplace (CTEF), they are thawed and, if necessary, recultivated to the blastocyst stage; afterwards, assisted hatching is performed. Results: In the period from January 2018 to July 2020, 138 selected suitable clients were asked for donations, with 52 not responding, 19 terminating and 29 extending the embryo storage. Only 38 clients, i.e. 27.5%, agreed with the usage of their embryos for the preparation of hESCs. In the same period, personal communication with suitable CAR clients took place and another 17 embryo donors were obtained. A total of 160 embryos were obtained from 55 donors aged 26 to 42 years. The embryos were most often frozen in the blastocyst (53 embryos – 33.1%) and morula (74 embryos – 46.3%) stages. Of the 29 genetically examined embryos, only 5 are euploid (17.2%), 2 are mosaic and 22 are aneuploid or with translocations or carriers with a monogenic defect. Conclusion: We have an informed consent prepared and approved by the Ethics Committee of the Masaryk University and the University Hospital Brno; 160 donated embryos have been selected and secured. A transport protocol and handover methodology are developed. The plan for the transfer of thawed anonymized embryos in the first phase, October – December 2020, includes approximately 5 thawed blastocysts per week with assisted hatching. After their transfer to the CTEF, the embryoblast will be isolated with subsequent cultivation. The established hESCs must meet the specified criteria of safety, stability and pluripotency. We believe that, in accordance with the project plan, we will obtain at least 3 clinical-grade hESC lines, the first created in the Czech Republic, respecting the requirements for Advanced Medicinal Therapy Products (AMTP).
Garlic is a well-known example of natural self-defence system consisting of an inactive substrate (alliin) and enzyme (alliinase) which, when combined, produce highly antimicrobial allicin. Increase of alliinase stability and its activity are of paramount importance in various applications relying on its use for in-situ synthesis of allicin or its analogues, e.g., pulmonary drug delivery, treatment of superficial injuries, or urease inhibitors in fertilizers. Here, we discuss the effect of temperature, pH, buffers, salts, and additives, i.e. antioxidants, chelating agents, reducing agents and cosolvents, on the stability and the activity of alliinase extracted from garlic. The effects of the storage temperature and relative humidity on the stability of lyophilized alliinase was demonstrated. A combination of the short half-life, high reactivity and non-specificity to particular proteins are reasons most bacteria cannot deal with allicin's mode of action and develop effective defence mechanism, which could be the key to sustainable drug design addressing serious problems with escalating emergence of multidrug-resistant (MDR) bacterial strains.
- MeSH
- Anti-Bacterial Agents pharmacology MeSH
- Bacteria drug effects ultrastructure MeSH
- Biocatalysis drug effects MeSH
- Time Factors MeSH
- Garlic enzymology MeSH
- Chemical Phenomena * MeSH
- Disulfides chemistry metabolism MeSH
- Kinetics MeSH
- Hydrogen-Ion Concentration MeSH
- Sulfinic Acids chemistry metabolism MeSH
- Carbon-Sulfur Lyases metabolism MeSH
- Freeze Drying MeSH
- Microbial Sensitivity Tests MeSH
- Microbial Viability drug effects MeSH
- Buffers MeSH
- Enzyme Stability drug effects MeSH
- Stereoisomerism MeSH
- Temperature MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
In the context of ongoing climate change, expected temperature rise may significantly limit plant growth and productivity of crop species. In this study, we investigated the effects of a sub-optimal temperature on buckwheat, a pseudocereal known for its nutraceutical advantages. Two buckwheat species differing by their reproduction method, namely Fagopyrum esculentum and Fagopyrum tataricum were grown at 21 °C and 27 °C in growth chambers. High temperature increased leaf production mainly in F. tataricum but decreased leaf area in both species. Water and photosynthesis-related parameters were affected by high temperature but our results suggested that although transpiration rate was increased, adaptive mechanisms were developed to limit the negative impact on photosynthesis. High temperature mainly affected the reproductive stage. It delayed flowering time but boosted inflorescence and flower production. Nevertheless, flower and seed abortions were observed in both species at 27 °C. Regarding flower fertility, heat affected more the female stage than the male stage and reduced the stigma receptivity. Pollen production increased with temperature in F. esculentum while it decreased in F. tataricum. Such discrepancy could be related to the self-incompatibility of F. esculentum. Both species increased their antioxidant production under high temperature to limit oxidative stress and antioxidant capacity was higher in the inflorescences than in the leaves. Total flavonoid content was particularly increased in the leaves of F. esculentum and in the inflorescences of F. tataricum. Altogether, our results showed that even if high temperature may negatively affect reproduction in buckwheat, it improves its antioxidant content.
OBJECTIVE: As adolescent cancer patients may suffer from infertility following treatment, fertility counselling is essential. Our aim was to explore the current situation in four European countries in terms of (I) education about the risk for infertility, (II) counselling on fertility preservation, (III) patients' knowledge on fertility, (IV) sufficiency of information and (V) uptake of cryopreservation. METHODS: In total, 113 patients (13-20 years) at 11 study centres completed a self-report questionnaire three and six months after cancer diagnosis. Multivariate logistic regression was used to estimate odds ratios (OR) with 95% confidence intervals (CI). RESULTS: As many as 80.2% of participants reported having received education about the risk for infertility prior to treatment, 73.2% recalled counselling on fertility preservation. Only 52.3% stated they felt sufficiently informed to make a decision. Inability to recall counselling on fertility preservation (OR = 0.03, CI: 0.00-0.47) and female gender (OR = 0.11, CI: 0.03-0.48) was associated with lower use of cryopreservation, whereas older age was associated with higher use. CONCLUSION: Fertility counselling was available to a relatively high proportion of patients, and it did influence the utilisation of cryopreservation. However, many patients did not feel sufficiently informed. Further improvement is needed to enable adolescent cancer patients to make an informed decision on fertility preservation.
- MeSH
- Infertility * prevention & control MeSH
- Humans MeSH
- Adolescent MeSH
- Neoplasms * therapy MeSH
- Counseling MeSH
- Aged MeSH
- Fertility Preservation * MeSH
- Check Tag
- Humans MeSH
- Adolescent MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Geographicals
- Europe MeSH
V České republice probíhá již 16 let celonárodní organizovaný screening nádorů prsu. Je kontrolovaný po stránce kvality i datových výstupů. Úmrtnost na nejčastější nádorové onemocnění žen poklesla v ČR o 30 %. Preventivní péče o prsní žlázu se liší podle věku. Ve fertilním období do 40 let věku se musí klást důraz na samovyšetřování a podpůrná ultrazvuková vyšetření. Je však nezbytné, aby byl program preventivní péče pro ženy v předscreeningovém věku individuální, základem je zvážení osobního rizika. Od 40 let věku se zvyšuje zobrazitelnost prsní žlázy v mamografii, která je jedinou ověřenou metodou snižující úmrtnost. Využití mamografie mezi 40.–45. rokem není zatím v evropských doporučeních standardem. Mamografie je zde vhodná pro ženy s vyšším osobním rizikem a také pro ženy, které samy chtějí začít s prevencí dříve, než ve stanoveném věku 45 let. Úkolem praktického lékaře je znát pravidla péče o prsní žlázu u žen všech věkových kategorií, zejména dohlížet na pravidelnou účast v celonárodním screeningu. Praktičtí lékaři se také významně podílejí na preventivních programech i u pacientů, kteří již byli pro některý zhoubný nádor léčeni. Zde je cílem včasný záchyt každé další malignity, kterou jsou pacienti ohroženi více než dosud zdravá populace.
In the Czech Republic the audited countrywide breast cancer screening has been already successfully functional for sixteen years, including regular quality control and outcome data presentations. Thus, breast cancer mortality in the Czech Republic has been reduced by 30%. Generally speaking, the preventive measures of woman´s breast care are age-dependent. In fertile period under 40 years of age only the self-examination of breast is indicated, complemented by ultrasonography when needed. Preventive care in pre-screening age, i.e.under 45, should be based on individual decision with awareness of relevant risk factors. Since 40 years of age the transparency of breast tissue is increasing in mammography, which thereafter becomes the prime and only preventive method proved as effective for reduction of breast cancer mortality. For age interval 40–45, however, the preventive use of mammography has not been yet adopted in Europan countries, but can be recommended for women with higher risk of cancer or willing to start with preventive mammography earlier than since 45 years. Every general practitioner (GP) should be aware of rules of preventive breast examination and be able to supervise participation of registered women in national breast cancer screening program. GPs should also actively recognize and recommend for breast cancer screening all women with any previous oncological record. These women certainly possess the higher inherent risk of any cancer, including breast, than a healthy population.
- MeSH
- Early Detection of Cancer MeSH
- Adult MeSH
- Humans MeSH
- Mammography MeSH
- Breast Neoplasms * diagnosis prevention & control MeSH
- Mass Screening MeSH
- Ultrasonography, Mammary MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Female MeSH
- Publication type
- Review MeSH
The pre-whole genome duplication (WGD) Zygosaccharomyces clade comprises several allodiploid strain/species with industrially interesting traits. The salt-tolerant yeast ATCC42981 is a sterile and allodiploid strain which contains two subgenomes, one of them resembling the haploid parental species Z. rouxii. Recently, different mating-type-like (MTL) loci repertoires were reported for ATCC42981 and the Japanese strain JCM22060, which are considered two stocks of the same strain. MTL reconstruction by direct sequencing approach is challenging due to gene redundancy, structure complexities, and allodiploid nature of ATCC42981. Here, DBG2OLC and MaSuRCA hybrid de novo assemblies of ONT and Illumina reads were combined with in vitro long PCR to definitively solve these incongruences. ATCC42981 exhibits several chimeric MTL loci resulting from reciprocal translocation between parental haplotypes and retains two MATa/MATα expression loci, in contrast to MATα in JCM22060. Consistently to these reconstructions, JCM22060, but not ATCC42981, undergoes mating and meiosis. To ascertain whether the damage of one allele at the MAT locus regains the complete sexual cycle in ATCC42981, we removed the MATα expressed locus by gene deletion. The resulting MATa/- hemizygous mutants did not show any evidence of sporulation, as well as of self- and out-crossing fertility, probably because incomplete silencing at the chimeric HMLα cassette masks the loss of heterozygosity at the MAT locus. We also found that MATα deletion switched off a2 transcription, an activator of a-specific genes in pre-WGD species. These findings suggest that regulatory scheme of cell identity needs to be further investigated in Z. rouxii protoploid yeast.
- Publication type
- Journal Article MeSH