Selective replication and vertical transmission of Ebola virus in experimentally infected Angolan free-tailed bats.

The natural reservoir of Ebola virus (EBOV), agent of a zoonosis burdening several African countries, remains unidentified, albeit evidence points towards bats. In contrast, the ecology of the related Marburg virus is much better understood; with experimental infections of bats being instrumental for understanding reservoir-pathogen interactions. Experiments have focused on elucidating reservoir competence, infection kinetics and specifically horizontal transmission, although, vertical transmission plays a key role in many viral enzootic cycles. Herein, we investigate the permissiveness of Angolan free-tailed bats (AFBs), known to harbour Bombali virus, to other filoviruses: Ebola, Marburg, Taï Forest and Reston viruses. We demonstrate that only the bats inoculated with EBOV show high and disseminated viral replication and infectious virus shedding, without clinical disease, while the other filoviruses fail to establish productive infections. Notably, we evidence placental-specific tissue tropism and a unique ability of EBOV to traverse the placenta, infect and persist in foetal tissues of AFBs, which results in distinct genetic signatures of adaptive evolution. These findings not only demonstrate plausible routes of horizontal and vertical transmission in these bats, which are expectant of reservoir hosts, but may also reveal an ancillary transmission mechanism, potentially required for the maintenance of EBOV in small reservoir populations.

Dynamical entropic measure of nonclassicality of phase-dependent family of Schrödinger cat states.

The phase-space approach based on the Wigner distribution function is used to study the quantum dynamics of the three families of the Schrödinger cat states identified as the even, odd, and Yurke-Stoler states. The considered states are formed by the superposition of two Gaussian wave packets localized on opposite sides of a smooth barrier in a dispersive medium and moving towards each other. The process generated by this dynamics is analyzed regarding the influence of the barrier parameters on the nonclassical properties of these states in the phase space below and above the barrier regime. The performed analysis employs entropic measure resulting from the Wigner-Rényi entropy for the fixed Rényi index. The universal relation of this entropy for the Rényi index equal one half with the nonclassicality parameter understood as a measure of the negative part of the Wigner distribution function is proved. This relation is confirmed in the series of numerical simulations for the considered states. Furthermore, the obtained results allowed the determination of the lower bound of the Wigner-Rényi entropy for the Rényi index greater than or equal to one half.

Effects of epidural analgesia on the course of labor.

OBJECTIVE: The aim of this study was to assess the effects of epidural analgesia on the course of labor. SUBJECTS AND METHODS: The material for the study was obtained from the analysis of 300 medical records of patients delivering under epidural analgesia in the period 2015-2019. A questionnaire by the authors was used as the research tool. Statistical analysis was performed using Fisher's test, Pearson's Chi-square test of independence, and Cramer's V-test. RESULTS: The first stage of labor in primiparas usually lasted six to nine hours, and in multiparas under five hours (p = 0.041). The second stage was shorter in multiparas (p < 0.001). Our five-year analysis demonstrated that the second stage of labor was longer from year to year (p = 0.087). The fetal station had an effect on the duration of the first stage of labor (p = 0.057). After administration of epidurals, the majority of the women bore the pain well (p = 0.052). CONCLUSIONS: Epidural analgesia reduces labor pain, but may also disturb the natural rhythm of labor. This happens even if the moment of application of the analgesia is chosen with the guidance of obstetric indications, and may result in the necessity for surgical intervention.

The impact of premenstrual syndrome on women's quality of life - a myth or a fact?

OBJECTIVE: The aim of this study was to assess the quality of life (QoL) of women with premenstrual syndrome (PMS). PATIENTS AND METHODS: The study involved 231 regularly menstruating women aged 18 years and older. The research was carried out from July 2018 to November 2018 at St. Maksymilian Maria Kolbe Catholic Secondary School in Szczecin, Non-Public Healthcare Center "MEDI-PLUS" in Zwierzyno, and by electronic means. The research instruments used in the study were: the author's questionnaire concerning the severity of individual PMS symptoms (based on the APA criteria for PMDD, included in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed.), and the standardized World Health Organization Quality of Life (WHOQOL-BREF) questionnaire. Statistical analysis was performed using the SPSS 24 statistical package. The Kolmogorov-Smirnov test was used. The level of statistical significance was set as p < 0.05. RESULTS: The QoL of women with PMS was at a medium level. Emotional symptoms were the most severe ones (p = 0.010). The highest QoL scores were obtained for the social relationship domain (p = 0.002), and the lowest for the mental health domain (p = 0.006). CONCLUSIONS: PMS involves significant morbidity, and the health burden it causes is still not fully assessed. Young women constitute a group that shows the greatest need for psychological support because they experience the most severe PMS symptoms.

Inoculation route-dependent Lassa virus dissemination and shedding dynamics in the natural reservoir - Mastomys natalensis.

Lassa virus (LASV), a Risk Group-4 zoonotic haemorrhagic fever virus, affects sub-Saharan African countries. Lassa fever, caused by LASV, results in thousands of annual deaths. Although decades have elapsed since the identification of the Natal multimammate mouse (Mastomys natalensis) as a natural reservoir of LASV, little effort has been made to characterize LASV infection in its reservoir. The natural route of infection and transmission of LASV within M. natalensis remains unknown, and the clinical impact of LASV in M. natalensis is mostly undescribed. Herein, using an outbred colony of M. natalensis, we investigate the replication and dissemination dynamics of LASV in this reservoir following various inoculation routes. Inoculation with LASV, regardless of route, resulted in a systemic infection and accumulation of abundant LASV-RNA in many tissues. LASV infection in the Natal multimammate mice was subclinical, however, clinical chemistry values were transiently altered and immune infiltrates were observed histologically in lungs, spleens and livers, indicating a minor disease with coordinated immune responses are elicited, controlling infection. Intranasal infection resulted in unique virus tissue dissemination dynamics and heightened LASV shedding, compared to subcutaneous inoculation. Our study provides important insights into LASV infection in its natural reservoir using a contemporary infection system, demonstrating that specific inoculation routes result in disparate dissemination outcomes, suggesting intranasal inoculation is important in the maintenance of LASV in the natural reservoir, and emphasizes that selection of the appropriate inoculation route is necessary to examine aspects of viral replication, transmission and responses to zoonotic viruses in their natural reservoirs.

The influence of support and medical data on the level of illness acceptance, the way of coping with a stressful situation, and mental adjustment to the disease among cancer patients.

OBJECTIVE: The aim of this study was to analyze the behavior of cancer patients. PATIENTS AND METHODS: This survey-based study involved 145 oncological patients and was conducted from July to November 2018. It was performed using an author's questionnaire and three standardized tools: the mini-Mental Adjustment to Cancer Scale, the Acceptance of Illness Scale, and the Coping Inventory for Stressful Situations. RESULTS: The acceptance of illness was at a medium level. Patients who had been ill for longer time periods coped with stress better (p < 0.071) and showed better mental adjustment (p < 0.05 for Positive Redefinition, and p < 0.08 for Fighting Spirit). Patients with benign tumors focused on emotions (p < 0.001) and avoidance (p < 0.005) and were preoccupied with anxiety (p < 0.05). Longer treatment time was associated with a higher ability to cope with stress (p < 0.05). Patients receiving support were characterized by Anxious Preoccupation attitude (p < 0.1), and those who had not got it by Fighting Spirit (p < 01). CONCLUSIONS: Cancer patients have problems coping with new circumstances. They need support and help to understand and accept their situation.

Can personality traits affect the quality of life of women with the BRCA1/BRCA2 mutations before and after prophylactic adnexectomy?

OBJECTIVE: Ovarian, fallopian tube, and peritoneal carcinomas are the most common hereditary gynecological cancers associated with the BRCA1 and BRCA2 mutations. It is recommended to radicalize management, using RRSO. Personality traits are regarded as significant contributors to human QoL and adaptability to the changed conditions of functioning. The aim of this study was to demonstrate the effect of personality on the QoL of women with the BRCA1 and BRCA2 mutations before and after RRSO. PATIENTS AND METHODS: The study involved 62 patients with the BRCA1 and BRCA2 mutations referred to hospital for RRSO. The research instruments were the WHQ, NEO-FFI, and self-developed sociodemographic data collection tool. RESULTS: Highly neurotic patients with the BRCA1 and BRCA2 mutations had lower QoL, especially in the domains of depressed mood, anxiety/fears, and sleep problems. At the same time, higher levels of conscientiousness, openness to experience, extroversion, and agreeableness were associated with better QoL outcomes. CONCLUSIONS: (1) Personality traits can contribute to the QoL of women with the BRCA1 and BRCA2 mutations before and after RRSO. (2) Identification of personality traits may be an important prognostic factor indicating potential changes in the QoL of patients after RRSO.

Oocyte matched follicular fluid anti-Müllerian hormone is an excellent predictor of live birth after fresh single embryo transfer.

STUDY QUESTION: What is the relationship between the anti-Müllerian hormone (AMH), gonadotropin and androgen concentrations within a single follicle and live birth after ICSI and a transfer of an embryo developed from the matched oocyte? SUMMARY ANSWER: Among the analysed markers on the day of oocyte retrieval, AMH concentration in follicular fluid (FF) is a predictor of live birth after single embryo transfer (SET). WHAT IS KNOWN ALREADY: High serum concentrations of AMH and low FSH concentrations have been associated with a high chance of pregnancy after ART. Whether there are differences in the hormonal milieu for individual follicles and whether this impacts the laboratory and clinical outcomes for the individual oocyte developing within that follicle are unknown. STUDY DESIGN, SIZE, DURATION: This prospective cohort study included 322 individual FF samples from 199 infertile women scheduled for ICSI/SET over an 18-month period. Of these women, 76 provided a single FF sample, while 123 women contributed two FF samples taken from two different follicles. PARTICIPANTS/MATERIALS, SETTING, METHODS: The first follicle aspirated in each ovary on the day of oocyte retrieval had the FF aspirated; the individual cumulus-oocyte complex (COC) was tracked, and the associated FF was stored at -80°C. FF AMH, FSH, LH, testosterone (T) and androstenedione (A2) levels were measured by mass spectrometry (androgens) and immunoassays. The laboratory and clinical outcomes for each individual oocyte were related to their unique follicle hormone concentrations. MAIN RESULTS AND THE ROLE OF CHANCE: Of the 322 oocytes with paired FF samples, 70 (21.7%) oocytes did not fertilise. From the remaining 252 2PN embryos, 88 (34.9%) were transferred as single embryos on Day 3; of the remaining 164, 78 developed into blastocysts, and 18 single blastocyst transfers were performed. Thus, a total of 106 transferred embryos had matching FF samples. An analysis of these individual FF concentrations revealed that AMH concentrations were higher in follicles in which the oocyte developed into a top quality (TQ) blastocyst (6.33 ± 5.52 ng/ml) and whose transfer led to live birth (7.49 ± 5.03 ng/ml) than those in which there was a failure of fertilisation (3.34 ± 2.21 ng/ml). In contrast, follicular FSH concentrations were the lower for oocytes that resulted in a TQ blastocyst (5.36 ± 2.20 mIU/ml) and live birth (5.60 ± 1.41 mIU/ml) than for oocytes that failed to fertilise (9.06 ± 3.36 mIU/ml). FF AMH was the only studied marker that increased the chance of live birth (odds ratio: 1.93 [95% CI: 1.40-2.67], P < 0.001). The receiver operating characteristic analysis showed that FF AMH levels predicted live birth with a very high sensitivity (91.2%), specificity (91.7%) and an excellent AUC value of 0.954, whereas serum AMH level only had a fair (AUC = 0.711) significance as a predictor for live birth after ICSI/SET. The predictive capabilities of the interfollicular markers were not limited to the TQ embryos or blastocysts; they applied to all SET cycles. LIMITATIONS, REASONS FOR CAUTION: Whether an altered intrafollicular hormonal environment reflects the developmental capacity of the oocyte or defines cannot be determined from this cross-sectional analysis. Inclusion of 21 subjects with polycystic ovary syndrome (PCOS) may have biased the findings due to a unique intrafollicular milieu associated with PCOS. WIDER IMPLICATIONS OF THE FINDINGS: Our results suggest that highly competent human oocytes have an FF composition of AMH, FSH, T and A2 that is close to that in a natural cycle. Also, the relationships between intrafollicular AMH, gonadotropin and androgen levels in the same follicle support the hypothesis that FF AMH concentration may reflect granulosa cell proliferation during gonadotropin-stimulated follicle growth. Finally, the serum AMH concentration is markedly lower than the FF AMH concentration, with a moderate correlation between serum and FF AMH, implying ovarian follicle autonomy with regards to its secretory products. STUDY FUNDING/COMPETING INTEREST(S): The National Science Centre of Poland supported this work (grant number: N N407 217 040). The authors declare that there is no conflict of interest regarding the publication of this article.

Metagenomic sequencing at the epicenter of the Nigeria 2018 Lassa fever outbreak.

The 2018 Nigerian Lassa fever season saw the largest ever recorded upsurge of cases, raising concerns over the emergence of a strain with increased transmission rate. To understand the molecular epidemiology of this upsurge, we performed, for the first time at the epicenter of an unfolding outbreak, metagenomic nanopore sequencing directly from patient samples, an approach dictated by the highly variable genome of the target pathogen. Genomic data and phylogenetic reconstructions were communicated immediately to Nigerian authorities and the World Health Organization to inform the public health response. Real-time analysis of 36 genomes and subsequent confirmation using all 120 samples sequenced in the country of origin revealed extensive diversity and phylogenetic intermingling with strains from previous years, suggesting independent zoonotic transmission events and thus allaying concerns of an emergent strain or extensive human-to-human transmission.

The KASH-containing isoform of Nesprin1 giant associates with ciliary rootlets of ependymal cells.

Biallelic nonsense mutations of SYNE1 underlie a variable array of cerebellar and non-cerebellar pathologies of unknown molecular etiology. SYNE1 encodes multiple isoforms of Nesprin1 that associate with the nuclear envelope, with large cerebellar synapses and with ciliary rootlets of photoreceptors. Using two novel mouse models, we determined the expression pattern of Nesprin1 isoforms in the cerebellum whose integrity and functions are invariably affected by SYNE1 mutations. We further show that a giant isoform of Nesprin1 associates with the ciliary rootlets of ependymal cells that line brain ventricles and establish that this giant ciliary isoform of Nesprin1 harbors a KASH domain. Whereas cerebellar phenotypes are not recapitulated in Nes1gSTOP/STOP mice, these mice display a significant increase of ventricular volume. Together, these data fuel novel hypotheses about the molecular pathogenesis of SYNE1 mutations and support that KASH proteins may localize beyond the nuclear envelope in vivo.

Murder with Radioactive Polonium Metal.

The physical and biological aspects of polonium-210, one of the most hazardous radioisotopes, are summarized. Although this radioisotope is naturally occurring and rare, it received quite a bit of attention after it was used in the 2006 assassination of former Russian Intelligence member Alexander Litvinenko in London. Recent reports on the suspected murder of Yasser Arafat with polonium-210 are also discussed.

[BEO'S - physical activity and healthy eating at schools in Oberfranken, Bavaria concept and first results of a resource-oriented, systemic approach in school-based health promotion]. / BEO'S - Bewegung und Ernährung an Oberfrankens Schulen Konzept und Erfahrungen bei der Umsetzung eines ressourcenorientierten, systemischen Ansatzes zur schulischen Gesundheitsförderung.

BACKGROUND: The high prevalence of overweight among children and adolescents has led to an increase in school-based prevention programmes. The aim of the present paper is to present the concept of an initiative called "BEO'S" as well as the experience made with the implementation und acceptance of this programme in the participating schools. METHODS: Different from the majority of school-based projects for healthy eating and physical activity, BEO'S pursues a systemic approach that includes the whole school and is tailored to the school's respective resources. Characteristics are (1) the participation of teachers, students, parents, and caretakers, (2) the motivation and empowerment of schools to plan and implement activities by themselves, (3) the focus on environmental approaches, and (4) addressing and considering the individual school's needs and resources. The university project team supports the schools by individual counselling as well as providing information materials, trainings and workshops for teachers, an internet page, newsletters, and financial support. In the school years 2007/08 and 2008/09, BEO'S was conducted at 14 primary and secondary schools in the district of Oberfranken, Bavaria. It was extended to other schools in 2009/10. The short- and mid-term goals are the improvement of the school's environments as well as the eating behaviour and physical activity of the students. In the long run, it is intended to prevent obesity and improve the students' health and school performance. RESULTS: The implementation processes showed that the teachers for physical education and domestic science as well as the headmasters were especially committed. The participation of the teaching staff, the students and the parents proved to be difficult, however. The schools implemented many activities for healthy eating and physical activity, but the planning process was not very systematic: needs assessment, status quo analysis, identification of successful strategies and definition of aims was difficult for the schools. The provided financial support, training programmes and workshops, and the exchange with other schools were widely used, in contrast to the offered internet-based tools. The acceptance of BEO'S was (very) good by teachers (n=97), students (n=674) and their parents (n=522). The teachers preferred the workshops and trainings to the internet page. The students appreciated the possibilities for physical activity and the emphasis on healthy eating; primary school students and girls more than secondary school students and boys. One third of the parents would like to be involved to a higher degree. CONCLUSION: BEO'S was well received by all the people involved. Yet, there are still deficits concerning the implementation process, especially in the participation of students and parents.

Core features of frontotemporal dementia recapitulated in progranulin knockout mice.

Frontotemporal dementia (FTD) is typified by behavioral and cognitive changes manifested as altered social comportment and impaired memory performance. To investigate the neurodegenerative consequences of progranulin gene (GRN) mutations, which cause an inherited form of FTD, we used previously generated progranulin knockout mice (Grn-/-). Specifically, we characterized two cohorts of early and later middle-aged wild type and knockout mice using a battery of tests to assess neurological integrity and behavioral phenotypes analogous to FTD. The Grn-/- mice exhibited reduced social engagement and learning and memory deficits. Immunohistochemical approaches were used to demonstrate the presence of lesions characteristic of frontotemporal lobar degeneration (FTLD) with GRN mutation including ubiquitination, microgliosis, and reactive astrocytosis, the pathological substrate of FTD. Importantly, Grn-/- mice also have decreased overall survival compared to Grn+/+ mice. These data suggest that the Grn-/- mouse reproduces some core features of FTD with respect to behavior, pathology, and survival. This murine model may serve as a valuable in vivo model of FTLD with GRN mutation through which molecular mechanisms underlying the disease can be further dissected.

Rapid and sensitive detection of Pseudomonas aeruginosa in chlorinated water and aerosols targeting gyrB gene using real-time PCR.

AIMS: For the rapid detection of Pseudomonas aeruginosa from chlorinated water and aerosols, gyrB gene-based real-time PCR assay was developed and investigated. METHODS AND RESULTS: Two novel primer sets (pa722F/746MGB/899R and pa722F/746MGB/788R) were designed using the most updated 611 Pseudomonas and 748 other bacterial gyrB genes for achieving high specificity. Their specificity showed 100% accuracy when tested with various strains including clinical isolates from cystic fibrosis patients. The assay was tested with Ps. aeruginosa-containing chlorinated water and aerosols to simulate the waterborne and airborne transmission routes (detection limit 3·3 × 10² CFU per PCR-2·3 × 10³ CFU per PCR). No chlorine interference in real-time PCR was observed at drinking water level (c. 1 mg l⁻¹), but high level of chorine (12 mg l⁻¹) interfered the assay, and thus neutralization was needed. Pseudomonas aeruginosa in aerosol was successfully detected after capturing with gelatin filters with minimum 2 min of sampling time when the initial concentration of 104 CFU ml⁻¹ bacteria existed in the nebulizer. CONCLUSIONS: A highly specific and rapid assay (2-3 h) was developed by targeting gyrB gene for the detection of Ps. aeruginosa in chlorinated water and aerosols, combined with optimized sample collection methods and sample processing, so the direct DNA extraction from either water or aerosol was possible while achieving the desired sensitivity of the method. SIGNIFICANCE AND IMPACT OF THE STUDY: The new assay can provide timely and accurate risk assessment to prevent Ps. aeruginosa exposure from water and aerosol, resulting in reduced disease burden, especially among immune-compromised and susceptible individuals. This approach can be easily utilized as a platform technology for the detection of other types of micro-organisms, especially for those that are transmitted via water and aerosol routes, such as Legionella pneumophila.

Acute neonatal glucocorticoid exposure produces selective and rapid cerebellar neural progenitor cell apoptotic death.

There has been a growing controversy regarding the continued use of glucocorticoid therapy to treat respiratory dysfunction associated with prematurity, as mounting clinical evidence has shown neonatal exposure produces permanent neuromotor and cognitive deficits. Here we report that, during a selective neonatal window of vulnerability, a single glucocorticoid injection in the mouse produces rapid and selective apoptotic cell death of the proliferating neural progenitor cells in the cerebellar external granule layer and permanent reductions in neuronal cell counts of their progeny, the cerebellar internal granule layer neurons. Our estimates suggest that this mouse window of vulnerability would correspond in the human to a period extending from approximately 20 weeks gestation to 6.5 weeks after birth. This death pathway is critically regulated by the proapoptotic Bcl-2 family member Puma and is independent of p53 expression. These rodent data indicate that there exists a previously unknown window of vulnerability during which a single glucocorticoid exposure at clinically relevant doses can produce neural progenitor cell apoptosis and permanent cerebellar pathology that may be responsible for some of the iatrogenically induced neurodevelopmental abnormalities seen in children exposed to this drug. This vulnerability may be related to the physiological role of glucocorticoids in regulating programmed cell death in the mammalian cerebellum.

Shifting paradigms in Pseudomonas aeruginosa biofilm research.

Biofilms formed by Pseudomonas aeruginosa have long been recognized as a challenge in clinical settings. Cystic fibrosis, endocarditis, device-related infections, and ventilator-associated pneumonia are some of the diseases that are considerably complicated by the formation of bacterial biofilms, which are resistant to most current antimicrobial therapies. Due to intense research efforts, our understanding of the molecular events involved in P. aeruginosa biofilm formation, maintenance, and antimicrobial resistance has advanced significantly. Over the years, several dogmas regarding these multicellular structures have emerged. However, more recent data reveal a remarkable complexity of P. aeruginosa biofilms and force investigators to continually re-evaluate previous findings. This chapter provides examples in which paradigms regarding P. aeruginosa biofilms have been challenged, reflecting the need to critically re-assess what is emerging in this rapidly growing field. In this process, several avenues of research have been opened that will ultimately provide the foundation for the development of preventative measures and therapeutic strategies to successfully treat P. aeruginosa biofilm infections.

The immediate early gene early growth response gene 3 mediates adaptation to stress and novelty.

Stress and exploration of novel environments induce neural expression of immediate early gene transcription factors (IEG-TFs). However, as yet no IEG-TF has been shown to be required for the normal biological or behavioral responses to these stimuli. Here we show that mice deficient for the IEG-TF early growth response gene (Egr) 3, display accentuated behavioral responses to the mild stress of handling paralleled by increased release of the stress hormone corticosterone. Egr3-/- mice also display abnormal responses to novelty, including heightened reactivity to novel environments and failure to habituate to social cues or startling acoustic stimuli. In a Y-maze spontaneous alternation task, they perform fewer sequential arm entries than controls, suggesting defects in immediate memory. Because stress and novelty stimulate hippocampal long-term depression (LTD), and because abnormalities in habituation to novelty and Y-maze performance have been associated with LTD deficits, we examined this form of synaptic plasticity in Egr3-/- mice. We found that Egr3-/- mice fail to establish hippocampal LTD in response to low frequency stimulation and exhibit dysfunction of an ifenprodil-sensitive (NR1/NR2B) N-methyl-d-aspartate receptor subclass. Long term potentiation induction was not altered. The NR2B-dependent dysfunction does not result from transcriptional regulation of this subunit by Egr3, because NR2B mRNA levels did not differ in the hippocampi of Egr3-/- and control mice. These findings are the first demonstration of the requirement for an IEG-TF in mediating the response to stress and novelty, and in the establishment of LTD.

Haemophilia in Poland.

The primary aim of this study was to analyse the data on 2269 haemophilic patients in the Polish National Register of Inherited Bleeding Disorders -- 1953 haemophilia A patients and 316 haemophilia B patients. Haemophilia A occurred in 1512 families, haemophilia B in 240 families. In the majority of haemophilia A and B cases severe haemophilia prevailed (59.7% and 56.6% respectively). In about 50% of haemophilic patients, no family history of bleeding diathesis was reported. For haemophilia A patients the mean age was 30.9 years and for haemophilia B patients, 29.2 years. Prevalence of haemophilia in Poland is approximately 1:12 300 inhabitants (1:5600 males). The second aim was to describe the orthopaedic status of severe haemophilia patients and to relate this status to the type of replacement therapy they received prior to the study. Ninety-two severe haemophilia patients (median age 26.0 years) were enrolled in the study. Right and left knee, elbow and ankle joints were evaluated clinically using the Gilbert scale. X-ray examinations were evaluated according to the Pettersson scale. Knee joints proved to be most affected. Eighty-four patients (91.3%) reported pain. Only one scored 0 on the Gilbert scale, another on the Pettersson scale. Thirty-seven per cent of patients used orthopaedic equipment, either occasionally or constantly. Twenty-five per cent had a history of orthopaedic surgery. Thirty-eight per cent were unemployed with some form of social subvention. On-demand treatment was applied. None of the patients received primary prophylaxis. The mean consumption of clotting factor concentrates was 68 054 IU per patient during the 12 months prior to the current study. These results indicate that in Poland all severe haemophilia patients above 20 years are affected by haemophilic arthropathy.

A single day of ethanol exposure during development has persistent effects on bi-directional plasticity, N-methyl-D-aspartate receptor function and ethanol sensitivity.

To determine factors that contribute to the learning deficits observed in individuals with fetal alcohol syndrome, we examined the effects of early postnatal ethanol exposure on forms of synaptic plasticity thought to underlie memory. Treatment of rat pups with ethanol on postnatal day 7 impaired the induction of N-methyl-D-aspartate receptor-dependent long-term potentiation and abolished homosynaptic long-term depression in the CA1 region of hippocampal slices prepared at postnatal day 30. An N-methyl-D-aspartate receptor-independent form of long-term potentiation induced by very high frequency stimulation could be induced in slices from ethanol-treated rats. Defects in long-term depression correlated with a diminished contribution of ifenprodil-sensitive N-methyl-D-aspartate receptors to synaptic transmission and defects in a spontaneous alternation behavioral task. Rats exposed to ethanol on postnatal day 7 also exhibited diminished sensitivity of synaptic N-methyl-D-aspartate receptors to block by ethanol at postnatal day 30 and decreased behavioral sedation to systemic ethanol injections. These results indicate that changes in synaptic plasticity and N-methyl-D-aspartate receptor function are likely to provide a neural substrate for the cognitive and behavioral changes that follow developmental ethanol exposure.