RESUMO
BACKGROUND: Musculoskeletal disorders are a leading cause of morbidity and the most prevalent source of disability among soldiers. Their high prevalence in armed forces and limited ressources have led to problems related to access to physical rehabilitation care. To increase access, supervised group-based exercise programs for the most prevalent musculoskeletal disorders (low back pain, patellofemoral pain, rotator cuff-related shoulder pain or lateral ankle sprain) have been developed at a Canadian Armed forces (CAF) base, but their effectiveness has not been evaluated. The primary objective of this randomized controlled trial is to evaluate the mid- and long-term effects of these group-based training programs on pain severity and functional limitations, in comparison with usual individual physiotherapy care. Secondary objectives include comparing both interventions in terms of health-related quality of life, pain-related fear, and patients' satisfaction. METHODS: One hundred and twenty soldiers with a new medical referral for physiotherapy services for one of the four targeted musculoskeletal disorders will be consecutively recruited. They will be randomly assigned to either group-based training program or usual individual physiotherapy care, and will take part in the assigned 12-week intervention. There will be four evaluation sessions over 26 weeks (baseline, week 6, 12 and 26). At each follow-up, functional limitations, pain severity, health-related quality of life and pain-related fears will be assessed. Patients satisfaction with treatment will also be evaluated at the end of the intervention period. Either two-way repeated measures ANOVA will be used to analyse and compare the effects of the interventions. DISCUSSION: This RCT will determine the effectiveness of group-based training programs compared to usual individual physiotherapy care. This new intervention model could represent an efficient, and more pro-active approach to manage a higher number of soldiers with musculoskeletal disorders. It could improve access to physical rehabilitation care and improve the health of soldiers. TRIAL REGISTRATION: ClinicalTrials.gov ( NCT05235152 ), February 11th 2022.
Assuntos
Militares , Canadá , Terapia por Exercício/efeitos adversos , Humanos , Modalidades de Fisioterapia , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Dor de Ombro/terapia , Resultado do TratamentoRESUMO
Shape parameters of a weakly deformed ground-state band and highly deformed slightly triaxial sideband in ^{42}Ca were determined from E2 matrix elements measured in the first low-energy Coulomb excitation experiment performed with AGATA. The picture of two coexisting structures is well reproduced by new state-of-the-art large-scale shell model and beyond-mean-field calculations. Experimental evidence for superdeformation of the band built on 0_{2}^{+} has been obtained and the role of triaxiality in the Aâ¼40 mass region is discussed. Furthermore, the potential of Coulomb excitation as a tool to study superdeformation has been demonstrated for the first time.
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The isospin mixing was deduced in the compound nucleus ^{80}Zr at an excitation energy of E^{*}=54 MeV from the γ decay of the giant dipole resonance. The reaction ^{40}Ca+^{40}Ca at E_{beam}=136 MeV was used to form the compound nucleus in the isospin I=0 channel, while the reaction ^{37}Cl+^{44}Ca at E_{beam}=95 MeV was used as the reference reaction. The γ rays were detected with the AGATA demonstrator array coupled with LaBr_{3}:Ce detectors. The temperature dependence of the isospin mixing was obtained and the zero-temperature value deduced. The isospin-symmetry-breaking correction δ_{C} used for the Fermi superallowed transitions was extracted and found to be consistent with ß-decay data.
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The properties of pygmy dipole states in 208Pb were investigated using the 208Pb(17O, 17O'γ) reaction at 340 MeV and measuring the γ decay with high resolution with the AGATA demonstrator array. Cross sections and angular distributions of the emitted γ rays and of the scattered particles were measured. The results are compared with (γ, γ') and (p, p') data. The data analysis with the distorted wave Born approximation approach gives a good description of the elastic scattering and of the inelastic excitation of the 2+ and 3- states. For the dipole transitions a form factor obtained by folding a microscopically calculated transition density was used for the first time. This has allowed us to extract the isoscalar component of the 1- excited states from 4 to 8 MeV.
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We have recently documented that trisomy 21 mosaicism is common in human foetal ovaries. On the basis of this observation we propose that the maternal age effect in Down syndrome (DS) is caused by the differential behaviour of trisomy 21 in relation to disomy 21 oocytes during development from foetal life until ovulation in adulthood. In particular, we suggest that trisomy 21 oocytes, lagging behind those that are disomic, may escape the timed pruning of the seven million in foetal life to the 300-400 finally selected for ovulation. The net effect of this preferential elimination will be an accumulation of trisomy 21 oocytes in the ovarian reserve of older women. We here highlight the implications of this Oocyte Mosaicism Selection (OMS) model with respect to the prevalent view that the maternal age effect is complex, dependent on many different biological and environmental factors. We examine conclusions drawn from recent large-scale studies in families, tracing DNA markers along the length of chromosome 21q between parents and DS children, in comparison to the OMS model. We conclude that these family linkage data are equally compatible with the maternal age effect originating from the accumulation of trisomy 21 oocytes with advancing maternal age. One relatively straightforward way to get to grips with what is actually going on in this regard would be to compare incidence of trisomy 21 oocytes (and their pairing configurations) in foetal ovaries with that in oocytes at the meiosis I stage from adult women.
Assuntos
Envelhecimento/genética , Síndrome de Down/genética , Idade Materna , Mosaicismo , Oócitos/crescimento & desenvolvimento , Ovário/embriologia , Ovário/crescimento & desenvolvimento , Envelhecimento/fisiologia , Cromossomos Humanos Par 21/genética , Feminino , Ligação Genética , Marcadores Genéticos , Humanos , Masculino , Modelos BiológicosRESUMO
Glial cells have been implicated in temporal lobe epilepsy in humans and in its models. Astrocytes are lost in several brain regions after acute seizures induced by pilocarpine and may suffer hyperplasia at subsequent time points. This study investigated the effect of N-methyl-(2S,4R)-trans-4-hydroxy-L-proline (NMP) on astrocytes exposed to cytotoxic concentrations of pilocarpine. Astrocytes were incubated with pilocarpine (half maximal inhibitory concentration (IC50)=31.86 mM) for 24 h. Afterwards, they were treated with NMP at concentrations ranging from 3.12 to 100 μg/mL for 24 h. Cell viability was assessed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cytoplasmic reactive oxygen species (ROS) and mitochondrial transmembrane potential (ΔΨm) were analyzed by flow cytometry using 2',7'-dichlorofluorescein diacetate (DCFH-DA) and rhodamine-123 (Rho123), respectively. Expression of glial fibrillary acidic protein (GFAP) and voltage-dependent anion channel-1 (VDAC-1) were measured by western blot. Pilocarpine significantly decreased cell viability and mitochondrial potential and increased ROS concentration significantly by 6.7 times compared to the control. NMP concentrations ≥25 µg/mL protected astrocytes against pilocarpine-induced injury in a concentration-dependent manner. Concomitantly, NMP reduced cytoplasmic ROS accumulation to 27.3, 24.8, and 12.3% in the groups treated with 25, 50, and 100 µg/mL NMP, respectively. NMP also protected mitochondria from pilocarpine-induced depolarization. These effects were associated with improvement of pilocarpine-induced GFAP and VDAC-1 overexpression, which are important biomarkers of astrocyte dysfunction. In conclusion, the improvement of ROS accumulation, VDAC-1 overexpression, and mitochondrial depolarization are possible mechanisms of the NMP protective action on reactive astrocytes.
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Our team has developed an experimental platform to evaluate the x-ray-generated stress and impulse in materials. Experimental activities include x-ray source development, design of the sample mounting hardware and sensors interfaced to the National Ignition Facility's diagnostics insertion system, and system integration into the facility. This paper focuses on the X-ray Transport and Radiation Response Assessment (XTRRA) test cassettes built for these experiments. The test cassette is designed to position six samples at three predetermined distances from the source, each known to within ±1% accuracy. Built-in calorimeters give in situ measurements of the x-ray environment along the sample lines of sight. The measured accuracy of sample responses as well as planned modifications to the XTRRA cassette is discussed.
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BACKGROUND: Trisomy 21 Down syndrome is the most common genetic cause for congenital malformations and intellectual disability. It is well known that in the outstanding majority of cases the extra chromosome 21 originates from the mother but only in less than 10 % from the father. The mechanism underlying this striking difference in parental origin of Trisomy 21 Down syndrome is still unknown. However, it seems likely that the main reason is a much higher stringency in the elimination of any trisomy 21 cells during fetal testicular than ovarian development. We have here focussed attention on the paternal gametic output, i.e. the incidence of disomy 21 in spermatozoa. RESULTS: We have used fluorescence in situ hybridisation (FISH) to determine the copy number of chromosome 21 in spermatozoa from 11 men with normal spermiograms. Due to the well-known risk of false positive and false negative signals using a single FISH probe, we have applied two chromosome 21q probes, and we have added a chromosome 18-specific probe to allow differentiation between disomy 21 and diploidy. Analysing a total number of 2000 spermatozoa per case, we documented an average incidence of disomy 21 at 0.13 %, with a range of 0.00-0.25 % and a SD of 0.08. There was no indication of diploidy in this cohort of 22,000 sperm. CONCLUSION: Numerous previous studies on the incidence of disomy 21 in sperm have been published, using FISH. As far as we are aware, none of these have applied more than a single chromosome 21-specific probe. Accepting our mean of 0.13 % of disomy 21, and providing there is no selective fertilisation capability of disomy 21 sperm in relation to the normal, we conclude that around 1 in 800 conceptions is expected to be trisomic for chromosome 21 of paternal origin. Bearing in mind that the maternal origin likely is at least 10 times more common, we tentatively propose that around 1 in 80 oocytes in the maternal ovarian reserve may be disomy 21. One reason for this discrepancy may be a more stringent selection against aberrant chromosome numbers during spermatogenesis than oogenesis. Further work is required to determine the relevant stages of spermatogenesis at which such a selection may take place.
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The glycophorin A (GPA) somatic mutation assay was performed to evaluate the magnitude of exposure to ionizing radiation among the human population living in the vicinity of the Semipalatinsk nuclear test site in Kazakhstan. All together, 113 blood samples were analyzed from three generations of people living in villages that were under the trail of the radioactive cloud from the first Soviet surface nuclear test performed in August 1949 and from later tests. The oldest generation (P0) lived in the area at the time of testing, whereas the younger generations (F1, F2) were exposed to smaller doses from the residual fallout and later tests. The GPA assay did not reveal significant differences in the variant cell frequencies for all subjects selected from the Semipalatinsk area compared with 74 matched controls living in a noncontaminated area. However, a significant increase (P < 0.05) in the mean allele-loss ON variant frequency was observed among the exposed P0 generation (12 x 10(-6)) in comparison to controls (7 x 10(-6)). Considering the sensitivity of the GPA assay, the results suggest that the mean dose to the P0 generation of the affected villages was relatively low, a finding which is in accordance to the conclusions obtained from other biological assays performed on the same population.
Assuntos
Genética Populacional , Glicoforinas/genética , Mutação , Adolescente , Adulto , Idoso , Criança , Feminino , Humanos , Cazaquistão , Masculino , Pessoa de Meia-IdadeRESUMO
Gastroesophageal reflux disease (GERD) is multifactorial disorder in which acid exposure has a central role in the mucosal damage, and the mainstay of medical treatment is the suppression of gastric acid secretion justifying the use of H2 receptors antagonists. In our study we compared the effects of ranitidine and ebrotidine, a novel H2 antagonist with gastroprotective properties, on the motor, pH and endoscopic aspects of GERD in randomized cross-over trial in humans. Twenty patients with endoscopic evidence of erosive esophagitis were included in the study. Esophageal manometry and 24-hour pH-metry were done with the use Synectics (Sweden) systems. The same examinations were repeated after 20 days period of treatment with either ranitidine or ebrotidine, given in single dose 300 and 800 mg (nocte) respectively. The pressure within the lower esophageal sphincter (LES) in the untreated and treated with ebrotidine or ranitidine patients remained lowered. Patients with GERD showed increase in duration and decrease in amplitude and propagation of peristaltic waves in the esophageal body which were not improved after treatment. Complete healing after 40 days of treatment was comparable with ebrotidine and ranitidine and averaged about 40%. The pH-metry showed improvement in treated patients in the reflux frequency and time pH below 4, ranitidine being more effective than ebrotidine. It can be concluded that GERD patients showed weaker primary peristalsis unrelated to LES pressure and treatment. Treatment with ebrotidine or ranitidine reduced significantly the endoscopic and self-assessment score, ebrotidine and ranitidine being equally effective in healing of esophageal mucosal lesions.
Assuntos
Antiulcerosos/farmacologia , Benzenossulfonatos/farmacologia , Refluxo Gastroesofágico/tratamento farmacológico , Ranitidina/farmacologia , Tiazóis/farmacologia , Adulto , Idoso , Método Duplo-Cego , Endoscopia , Esôfago/efeitos dos fármacos , Esôfago/fisiologia , Humanos , Concentração de Íons de Hidrogênio , Masculino , Pessoa de Meia-IdadeRESUMO
The aim of the study was to evaluate the neurotoxic effect of a dermally-applied mixture of chlorpyrifos and cypermethrin in rats based on cognitive function, activity of the blood cholinesterase and brain acetylcholinesterase, as well as histologic brain examination. Nurelle D 550 EC (500 g of chlorpyrifos and 50 g of cypermethrin) was used in the study. The application liquid was in the form of a water solution. The investigation covered eight groups of animals: six experimental groups and two control groups, of 15 rats each. Experimental groups received 5.6 mg/cm2 chlorpyrifos and 0.5 mg/cm2 cypermethrin, or 27.8 mg/cm2 chlorpyrifos and 2.7 mg/cm2 cypermethrin dermally, for one day, one week and four weeks, except for Saturdays and Sundays. The preparations examined were applied to the tail skin of rats. The animals were anaesthetized at the end of exposure period. Plasma cholinesterase and brain acetylcholinesterase activities were determined. The brain for histological examination was perfused with a solution of methanol, formalin and glacial acetic acid, and the sections stained by the Nissel method. The behaviour of the animals was evaluated in the open field test four times: before exposure, and after one, two and four weeks of the experiment. The results of the study showed that chlorpyrifos and cypermethrin applied in a mixture caused an inhibition of cholinesterase and acetylcholinesterase activity and elicited the pycnosis of brain neurocytes.
Assuntos
Encéfalo/efeitos dos fármacos , Clorpirifos/toxicidade , Inibidores da Colinesterase/toxicidade , Colinesterases/metabolismo , Inseticidas/toxicidade , Piretrinas/toxicidade , Acetilcolinesterase/metabolismo , Administração Tópica , Animais , Encéfalo/enzimologia , Encéfalo/patologia , Clorpirifos/farmacocinética , Inibidores da Colinesterase/farmacocinética , Relação Dose-Resposta a Droga , Feminino , Inseticidas/farmacocinética , Piretrinas/farmacocinética , Ratos , Ratos Wistar , Absorção Cutânea , Fatores de TempoRESUMO
The study was conducted on female and male Swiss mice with body mass of 20-30 g. The experimental animals were administered deltamethrin in concentrations of 5 mg/kg b.m. (1/10 LD50) and 25 mg/kg b.m. (1/2 LD50), or fenvalerate in the doses of 10 mg/kg b.m. (1/10 LD50) and 50 mg/kg b.m. (1/2 LD50). Pyrethroids were administered intragastrically once a day for 28 days. Parallel studies were conducted in two control groups. The following organs were taken for histologic examinations: liver, kidney, lung, heart and spleen. Blood was taken from the heart for hematologic tests. The total number of erythrocytes and leukocytes, the percentage of neutrophils and lymphocytes, as well as the level of hemoglobin and hematocrit were determined. Deltamethrin and fenvalerate caused degenerative changes in the liver and kidneys in Swiss mice. Changes were more intense in male mice which were administered deltamethrin, and in female mice which received fenvalerate. Irrespective of the dose, the pyrethroids examined stimulated erythropoiesis and synthesis of hemoglobin in male Swiss mice, while in female mice the administration of deltamethrin in the dose of 1/10 LD50 resulted in the suppression of erythropoiesis and hemoglobin synthesis. Both in male and female mice, deltamethrin and fenvalerate--irrespective of the dose--caused a general increase in the number of leukocytes.
Assuntos
Inseticidas/toxicidade , Piretrinas/toxicidade , Administração Oral , Animais , Contagem de Células Sanguíneas , Relação Dose-Resposta a Droga , Eritrócitos/efeitos dos fármacos , Feminino , Coração/efeitos dos fármacos , Hematócrito , Hemoglobinas/efeitos dos fármacos , Inseticidas/sangue , Inseticidas/farmacocinética , Rim/efeitos dos fármacos , Rim/patologia , Dose Letal Mediana , Leucócitos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/patologia , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Camundongos , Nitrilas , Piretrinas/sangue , Piretrinas/farmacocinética , Baço/efeitos dos fármacos , Baço/patologiaRESUMO
The effect of a synthetic pyrethroid - alpha-cypermethrin administered per os for 28 days to Swiss mice was examined on phagocytic and bactericidal activity of neutrophils, and leukocytic image, IL-12 p70 level in blood plasma, as well as histologic and ultrastructural picture of the liver, heart, kidneys, lung and spleen. A synthetic pyrethroid alpha-cypermethrin, [(R,S)-alpha-cyano-3-phenoxybenzyl (R,S)-cis,trans-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropanecarboxylate], produced by the Chemical Plant in Jaworzno was used in the study. The preparation for the application per os was used in doses 1/2 LD(50) (25 mg/kg body mass) and 1/5 LD(50) (10 mg/kg body mass). The results were presented as mean (x) +/- standard error (SEM) and subjected to statistical analysis by the parametric t-Student test. Subacute poisoning of mice with alpha-cypermethrin in doses 1/2 LD(50) and 1/5 LD(50) resulted in decreased bactericidal activity of neutrophils. The dose 10 mg/kg body mass had a stronger stimulatory effect on phagocytic activity than 25 mg/kg body mass. Significantly higher numbers of monocytes and lymphocytes were observed in the blood of male mice poisoned with 1/5 LD(50) alpha-cypermethrin. The administration of alpha-cypermethrin resulted for both doses in the decrease in IL-12 p70 serum secretion. The lowest IL-12 p70 level (pg/ml) was noted among female mice administered 1/2 LD(50) of the preparation. The results of the study may indicate that the pyrethroid in the study had a suppressive effect on Il-12 p70 production. In mice administered 1/5 LD(50) or 1/2 LD(50) of the preparation examined, histopathologic and ultrastructural changes were observed in the liver and kidneys.
Assuntos
Inseticidas/toxicidade , Piretrinas/toxicidade , Administração Oral , Animais , Peso Corporal , Contagem de Células , Feminino , Coração/efeitos dos fármacos , Inseticidas/administração & dosagem , Inseticidas/sangue , Inseticidas/farmacocinética , Interleucina-12/sangue , Rim/efeitos dos fármacos , Rim/ultraestrutura , Leucócitos/citologia , Leucócitos/efeitos dos fármacos , Leucócitos/imunologia , Fígado/efeitos dos fármacos , Fígado/ultraestrutura , Masculino , Camundongos , Fagocitose/efeitos dos fármacos , Piretrinas/administração & dosagem , Piretrinas/sangue , Piretrinas/farmacocinética , Baço/efeitos dos fármacosRESUMO
The production of beta-1,3-glucanases and chitinases by three strains of Trichoderma in submerged cultures was determined. The synthesis of enzymes was induced by cell wall biopolymers of phytopathogenic fungi (Botrytis cinerea, Fusarium culmorum and F. oxysporum). T. hamatum produced the highest beta-1,3-glucanase activity; the most effective inducer of enzyme synthesis was the biomass of F. oxysporum. All examined strains of Trichoderma inhibited phytopathogen growth in biotic tests. The diffusion tests showed that the lytic enzymes take part in growth inhibition of phytopathogenic fungi.
Assuntos
Botrytis/efeitos dos fármacos , Quitinases/farmacologia , Fusarium/efeitos dos fármacos , Trichoderma/enzimologia , beta-Glucosidase/farmacologia , Glucana 1,3-beta-Glucosidase , Testes de Sensibilidade Microbiana , Doenças das Plantas/microbiologia , Especificidade por Substrato , beta-Glucosidase/fisiologiaRESUMO
The paper evaluates the correlation between culture tested for Helicobacter pylori from biopsy material obtained from patients diagnosed with stomach ulcer, duodenal ulcer and gastritis, and the level of specific IgG antibodies measured by the ELISA test. As compared with culture, the ELISA test yielded a higher percentage of positive assays. Antibody titer was particularly raised in patients with duodenal ulcer, which accounted for 83% of cases. The highest frequency of positive cultures (50%) was also obtained in this group of patients. Essentially, the results are in agreement with findings reported by other authors.
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Técnicas de Tipagem Bacteriana , Gastroenteropatias/microbiologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/isolamento & purificação , Adulto , Idoso , Anticorpos Antibacterianos/análise , Biópsia , Úlcera Duodenal/diagnóstico , Úlcera Duodenal/microbiologia , Ensaio de Imunoadsorção Enzimática , Feminino , Gastroenteropatias/diagnóstico , Infecções por Helicobacter/diagnóstico , Humanos , Imunoglobulina G/análise , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos TestesRESUMO
The authors of the paper present the system designed for constant monitoring of the nosocomial infections. The system is based on the following data: 1. The chart on which the nosocomial infections are registered; the chart, added to the case record of every patient in the hospital, is prepared by a nurse in the admission quarters and it is homogenously filled in by the doctor when patient is discharged from the hospital. 2. Computer processing of the information included in the chart on which nosocomial infections are registered, with the use of IBM computer and a special prepared on the data base for DOS system.
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Infecção Hospitalar/prevenção & controle , Monitoramento Ambiental/métodos , Registros Hospitalares/estatística & dados numéricos , Controle de Infecções/organização & administração , Monitorização Fisiológica , Infecção Hospitalar/diagnóstico , Monitoramento Ambiental/estatística & dados numéricos , Controle de Formulários e Registros/métodos , Humanos , Controle de Infecções/métodos , Controle de Infecções/estatística & dados numéricos , PolôniaRESUMO
The aim of this study was to review 39 twin deliveries in the Department of Obstetrics in District Hospital in Lublin in 1998. The incidence of twin pregnancies was 2.01%. Eighteen patients (46.15%) were term at delivery whereas 21 (53.8%) were premature (mean gestational age at delivery 35 weeks). Vertex presentation of both twins was the most common with an incidence of 48.7% followed by vertex-nonvertex (25.6%) and non-vertex presentation of first twin (15.4%). Twenty patients (51.28%) delivered vaginally and 19 women (48.7%) underwent cesarean section including 2 cesarean birth of second twin after vaginal delivery of first twin. In our results, we conclude that the techniques of twin delivery, whether vaginal or by cesarean section, would depend on the judgement and expertise of the labour in twin gestations.
Assuntos
Parto Obstétrico/métodos , Parto Obstétrico/estatística & dados numéricos , Gravidez Múltipla/estatística & dados numéricos , Adulto , Cesárea/estatística & dados numéricos , Feminino , Humanos , Incidência , Apresentação no Trabalho de Parto , Trabalho de Parto Prematuro/epidemiologia , Polônia/epidemiologia , Gravidez , GêmeosRESUMO
As a part of the programme concerning iodine deficiency and iodine prophylaxis in Poland, 2518 children of age between 6 and 13 years, living in Lower and Middle Silesia, were studied. The anamnesis was based on a questionnaire answered by parents of the investigated children. The physical examination included measurements of body height and mass, clinical symptoms of thyroid functions as well as size and compactness of the thyroid gland on the basis of WHO classification. Urinary concentration of iodine was measured. The majority of children with goiter were inhabitants of mountainous villages. The goiter was most frequent in the age group 9-10 years. No significant differences in goiter incidence could be found between children consuming and not consuming iodized kitchen salt. The urinary concentration of iodine was low in all children examined. It was concluded that the territory of Lower and Middle Silesia is still a region of moderate endemic goiter. The urinary iodine concentrations is low in children living in Lower and Middle Silesia. The present system of iodine prophylaxis is not adequate and new measures should be urgently introduced.
Assuntos
Bócio Endêmico/epidemiologia , Adolescente , Criança , Feminino , Alimentos Fortificados , Bócio Endêmico/diagnóstico , Bócio Endêmico/prevenção & controle , Humanos , Iodo/deficiência , Iodo/uso terapêutico , Iodo/urina , Masculino , Polônia/epidemiologia , Prevalência , Cloreto de Sódio na Dieta , Glândula Tireoide/diagnóstico por imagem , UltrassonografiaRESUMO
It has now been over 50 years since it was discovered that Down syndrome is caused by an extra chromosome 21, i.e., trisomy 21. In the interim, it has become clear that in the majority of cases, the extra chromosome is inherited from the mother, and there is, in this respect, a strong maternal age effect. Numerous investigations have been devoted to clarifying the underlying mechanism, most recently suggesting that this situation is exceedingly complex, involving both biological and environmental factors. On the other hand, it has also been proposed that germinal trisomy 21 mosaicism, arising during the very early stages of maternal oogenesis with accumulation of trisomy 21 germ cells during subsequent development, may be the main predisposing factor. We present data here on the incidence of trisomy 21 mosaicism in a cohort of normal fetal ovarian samples, indicating that an accumulation of trisomy 21 germ cells does indeed take place during fetal oogenesis, i.e., from the first to the second trimester of pregnancy. We presume that this accumulation of trisomy 21 (T21) cells is caused by their delay in maturation and lagging behind the normal cells. We further presume that this trend continues during the third trimester of pregnancy and postnatally, up until ovulation, thereby explaining the maternal age effect in Down syndrome.
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BACKGROUND: It is now nearly a century since it was first discovered that crossovers between homologous parental chromosomes, originating at the Prophase stage of Meiosis I, are not randomly placed. In fact, the number and distribution of crossovers are strictly regulated with crossovers/chiasmata formed in optimal positions along the length of individual chromosomes, facilitating regular chromosome segregation at the first meiotic division. In spite of much research addressing this question, the underlying mechanism(s) for the phenomenon called crossover/chiasma interference is/are still unknown; and this constitutes an outstanding biological enigma. RESULTS: The Chromosome Oscillatory Movement (COM) model for crossover/chiasma interference implies that, during Prophase of Meiosis I, oscillatory movements of the telomeres (attached to the nuclear membrane) and the kinetochores (within the centromeres) create waves along the length of chromosome pairs (bivalents) so that crossing-over and chiasma formation is facilitated by the proximity of parental homologs induced at the nodal regions of the waves thus created. This model adequately explains the salient features of crossover/chiasma interference, where (1) there is normally at least one crossover/chiasma per bivalent, (2) the number is correlated to bivalent length, (3) the positions are dependent on the number per bivalent, (4) interference distances are on average longer over the centromere than along chromosome arms, and (5) there are significant changes in carriers of structural chromosome rearrangements. CONCLUSIONS: The crossover/chiasma frequency distribution in humans and mice with normal karyotypes as well as in carriers of structural chromosome rearrangements are those expected on the COM model. Further studies are underway to analyze mechanical/mathematical aspects of this model for the origin of crossover/chiasma interference, using string replicas of the homologous chromosomes at the Prophase stage of Meiosis I. The parameters to vary in this type of experiment will include: (1) the mitotic karyotype, i.e. ranked length and centromere index of the chromosomes involved, (2) the specific bivalent/multivalent length and flexibility, dependent on the way this structure is positioned within the nucleus and the size of the respective meiocyte nuclei, (3) the frequency characteristics of the oscillatory movements at respectively the telomeres and the kinetochores.