RESUMO
Escherichia coli FocA and FocB formate channels export formate or import it for further disproportionation by the formate hydrogenlyase (FHL) complex to H2 and CO2. Here, we show that under pH and osmotic stress FocA and FocB play important roles in regulating proton and potassium fluxes and couple this with H2 production in stationary-phase cells. Using whole-cell assays with glucose as electron donor, a focB mutant showed a 50 % decrease in VH2, while N'N'-dicyclohexylcarbodiimide (DCCD) treatment of osmotically stressed cells underlined the role of FOF1 ATPase in H2 production. At pH 7.5 and under osmotic stress FocB contributed to the proton flux but not to the potassium flux. At pH 5.5 both formate channels contributed to the proton and potassium fluxes. Particulalry, a focA mutant had 40 % lower potassium flux whereas the proton flux increased approximately two-fold. Moreover, at pH 5.5H2 production was totally inhibited by DCCD in the focA mutant. Taken together, our results suggest that depending on external pH, the formate channels play an important role in osmoregulation by helping to balance proton/potassium fluxes and H2 production, and thus assist the proton FOF1-ATPase in maintenance of ion gradients in fermenting stationary-phase cells.
Assuntos
Proteínas de Escherichia coli , Escherichia coli , Hidrogênio , Pressão Osmótica , Potássio , Prótons , Escherichia coli/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Proteínas de Escherichia coli/genética , Fermentação , Formiatos/metabolismo , Hidrogênio/metabolismo , Concentração de Íons de Hidrogênio , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/genética , Potássio/metabolismoRESUMO
The purpose of the study was to analyze functioning of the Department of telemedicine department over three-year period with assessment of main trends and regional characteristics, as well as the most significant results of telemedicine consultations. The step-wise analysis of applications for telemedicine consultation in 2019-2021 was carried out. They were conventionally classified by "in-coming" and "out-coming" information. At the first stage, number of applications received in 2019-2021 (n=10,145) was analyzed. The regional features of applications were established. At the second stage, extended analysis of all applications received in 2021 (n=4518) was carried out considering type of request, profile of request, fact of video communication, structure of directional diagnoses according the ICD-10 classes with identification of regional characteristics. At the third stage, sampling analysis of applications in 2021 (n=1000) was carried out with in-depth assessment of "in-coming" and "out-coming" information. The study established trend of annual increase of number of requests for telemedicine care (2,380 in 2019; 3,237 in 2020; 4,518 in 2021). The Privolzhsky Federal Okrug is leading in number of applications. The neurologists, rheumatologists and gastroenterologists are the most called-for specialists of somatic profile. The thoracic, neonatal and abdominal surgeons are the most-called specialists of surgical profile. This structure corresponded in whole to the structure of the ICD-10 classes that the region requested. The analysis of consultations testified high need in hospitals to transfer children to the Federal Center for treatment (57.6% of applications), that was not always justified. Therefore, positive decision about hospitalization was made less often (35% of cases). The recommendations of specialists of the National Medical Research Center for Children Health concerning treatment tactics (46% of applications) and additional examinations (44% of applications) were provided more often than it was indicated in application. The conclusion was made about increasing demand for and importance of telemedicine consultations in format "physician-physician" in pediatric practice and necessity of further research study with purpose to improve and optimize this type of medical care.
Assuntos
Pesquisa Biomédica , Telemedicina , Recém-Nascido , Humanos , Criança , Telemedicina/métodos , Encaminhamento e Consulta , Hospitais , HospitalizaçãoRESUMO
AIM: To determine factors of adherence to treatment in patients with ulcerative colitis (UC). MATERIALS AND METHODS: The study was performed in the department of treatment of inflammatory bowel diseases in Loginov Moscow Clinical Scientific Center from 2019 till 2021 years by surveying 1089 patients with UC. This analysis revealed patients with high adherence (HAP) and low adherence to treatment (LAP). RESULTS: In the survey analysis was determined, that there were more low-adherence patients, than high-adherence patients [596 (59.6%) and 404 (40.4%), respectively, (p0.001)]. In the group of HAP (100%) were 297 women (73.5%) and 107 (26.5%) men (p0.001). Also in this group prevailed patients with duration of disease more 5 years 305 (75.5%) and extraintestinal manifestations 261 (64.6%); p0.001. In the group of LAP (100%) were more patients younger 44 years, with bad habits and who did not follow diet (p0.001). The rate of UC reccurence more than 1 time per year was higher in LAP group 430 (72.1%), versus 137 (33.9%) patients in HAP (p0.001). The frequency of surgical procedures in UC patients was significantly higher in LAP 12 (2.0%) in comparison with 2 (0.5%) in HAP group (p0.001). CONCLUSION: In our study was determined, that among UC patients, examined in the department of inflammatory bowel diseases, 60% patients had low adherence to treatment. High adherence to the treatment is statistically significantly associated with female gender, family accommodation, non-working patients, extraintestinal manifestations, additional medical maintenance. Low adherence to the treatment is associated with steroids, male gender, age less than 44 year, bad habits (smoking, alcohol consumption), higher education, complicated UC and frequency of reccurences.
Assuntos
Colite Ulcerativa , Doenças Inflamatórias Intestinais , Feminino , Humanos , Masculino , Colite Ulcerativa/diagnóstico , Colite Ulcerativa/epidemiologia , Colite Ulcerativa/terapia , Doenças Inflamatórias Intestinais/complicações , Esteroides/uso terapêutico , Moscou/epidemiologiaRESUMO
Recently, almost all over the world attention of doctors and scientists is focused on a new coronavirus infection, the source of which was the causative agent SARS-CoV-2. In this regard, early diagnosis, including on the basis of symptoms from ENT organs, is crucial. A brief analysis of the available literature on the peculiarities of ENT organs manifestations in patients with SARS-CoV-2 is given. It was found out that to date there is very little data on the state of loro organs in patients with SARS-CoV-2 and no data on anosmia in the pediatric population. However, it is in children in the epidemic aspect that early diagnosis of infection and understanding of its key symptoms is of utmost importance.
Assuntos
Betacoronavirus , Infecções por Coronavirus , Otorrinolaringopatias , Pandemias , Pneumonia Viral , Betacoronavirus/isolamento & purificação , COVID-19 , Criança , Infecções por Coronavirus/complicações , Diagnóstico Precoce , Humanos , Otorrinolaringopatias/etiologia , Pneumonia Viral/complicações , SARS-CoV-2RESUMO
Here, we report on the outcome of the 2nd International Danube Symposium on advanced biomarker development that was held in Vienna, Austria, in early 2018. During the meeting, cross-speciality participants assessed critical aspects of non-invasive, quantitative biomarker development in view of the need to expand our understanding of disease mechanisms and the definition of appropriate strategies both for molecular diagnostics and personalised therapies. More specifically, panelists addressed the main topics, including the current status of disease characterisation by means of non-invasive imaging, histopathology and liquid biopsies as well as strategies of gaining new understanding of disease formation, modulation and plasticity to large-scale molecular imaging as well as integrative multi-platform approaches. Highlights of the 2018 meeting included dedicated sessions on non-invasive disease characterisation, development of disease and therapeutic tailored biomarkers, standardisation and quality measures in biospecimens, new therapeutic approaches and socio-economic challenges of biomarker developments. The scientific programme was accompanied by a roundtable discussion on identification and implementation of sustainable strategies to address the educational needs in the rapidly evolving field of molecular diagnostics. The central theme that emanated from the 2nd Donau Symposium was the importance of the conceptualisation and implementation of a convergent approach towards a disease characterisation beyond lesion-counting "lumpology" for a cost-effective and patient-centric diagnosis, therapy planning, guidance and monitoring. This involves a judicious choice of diagnostic means, the adoption of clinical decision support systems and, above all, a new way of communication involving all stakeholders across modalities and specialities. Moreover, complex diseases require a comprehensive diagnosis by converging parameters from different disciplines, which will finally yield to a precise therapeutic guidance and outcome prediction. While it is attractive to focus on technical advances alone, it is important to develop a patient-centric approach, thus asking "What can we do with our expertise to help patients?"
Assuntos
Biomarcadores/metabolismo , Congressos como Assunto/organização & administração , Imagem Molecular/métodos , Neoplasias/patologia , Relatório de Pesquisa , Áustria , Biomarcadores/análise , Humanos , Agências Internacionais , Imagem Molecular/instrumentação , Imagem Molecular/tendências , Neoplasias/diagnóstico por imagem , Neoplasias/metabolismo , Neoplasias/terapiaRESUMO
Real - life data on the effectiveness and safety of biosimilar and biologic drugs licensed for treatment of inflammatory bowel diseases (IBD) is lacking. AIM: To investigate efficacy of original Infliximab (IFX) and its biosimilar in treating patients with ulcerative colitis (UC) and determine the frequency of adverse events during 1 year follow - up period. MATERIALS AND METHODS: Our cohort consisted of 98 ulcerative colitis patients, treated with original IFX and its biosimilar since December 2017 till December 2018 years. Original Infliximab was prescribed in 56 UC patients (57.1%) during 5 years and longer; 16 patients (16.3%) were switched to IFX biosimilar; 13 UC bio - naïve patients (13.3%) received original IFX, 29 (29.6%) patients - biosimilar IFX. In 14 patients (14.3%) original infliximab was rotated with biosimilar. We picked out 42 patients to assess efficacy of original IFX and biosimilar. RESULTS AND DISCUSSION: Twelve patients, received original IFX and 28 patients, treated with its biosimilar, showed significant clinical improvement by decreasing Mayo index from 9.7±0.4 and 10.2±0.2 points to 1.9±0.09 and 2.1±0.1 points, accordingly. Also we noticed positive change in laboratory markers - CRP decrease from 89.6±8.7 mg/l and 77.5±8.0 mg/l to 6.5±0.8 mg/l and 6.9±0.8 mg/l (p>0.05), albumin increase from 30.1±4.7 g/l and 29.6±3.6 g/l to 34.1±6.3 g/l and 32.8±5.9 g/l (p>0.05), increase of serum iron levels from 6.4±0.5 mcg/l and 7.1±0.65 mcg/l to 14.6±4.4 mcg/l and 15.9±5.1 mcg/l (p>0.05), hemoglobin increase from 104.7±9.8 g/l and 102.2±8.8 g/l till 124±11.3 g/l and 121±10.9 g/l (p>0.05), and fecal calprotectin decrease from 1680±134 mcg/g and 1720±126 mcg/g till 245.5±33.4 mcg/g and 230.5±29.8 mcg/g (p>0.05). During 1 year follow - up 12 UC patients, treated with original IFX and its biosimilar, developed adverse events. The majority of adverse events (n=8) were registered in patients, rotating administration of original IFX and its biosimilar. CONCLUSION: IFX biosimilar is effective as well as original IFX. Frequency of adverse events, occurred in patients, treated with original IFX, was comparable with adverse events frequency in patients, received biosimilar IFX. Frequency of adverse events was significantly higher in UC patients, rotating original IFX and its biosimilar.
Assuntos
Medicamentos Biossimilares , Colite Ulcerativa , Fármacos Gastrointestinais , Infliximab , Anticorpos Monoclonais , Medicamentos Biossimilares/efeitos adversos , Estudos de Coortes , Colite Ulcerativa/tratamento farmacológico , Fármacos Gastrointestinais/efeitos adversos , Humanos , Infliximab/efeitos adversos , Indução de Remissão , Resultado do TratamentoRESUMO
Resting heart rate variability (HRV), an index of parasympathetic cardioregulation and an individual trait marker related to mental and physical health, decreases with age. Previous studies have associated resting HRV with structural and functional properties of the brain - mainly in cortical midline and limbic structures. We hypothesized that aging affects the relationship between resting HRV and brain structure and function. In 388 healthy subjects of three age groups (140 younger: 26.0⯱â¯4.2 years, 119 middle-aged: 46.3⯱â¯6.2 years, 129 older: 66.9⯱â¯4.7 years), gray matter volume (GMV, voxel-based morphometry) and resting state functional connectivity (eigenvector centrality mapping and exploratory seed-based functional connectivity) were related to resting HRV, measured as the root mean square of successive differences (RMSSD). Confirming previous findings, resting HRV decreased with age. For HRV-related GMV, there were no statistically significant differences between the age groups, nor similarities across all age groups. In whole-brain functional connectivity analyses, we found an age-dependent association between resting HRV and eigenvector centrality in the bilateral ventromedial prefrontal cortex (vmPFC), driven by the younger adults. Across all age groups, HRV was positively correlated with network centrality in the bilateral posterior cingulate cortex. Seed-based functional connectivity analysis using the vmPFC cluster revealed an HRV-related cortico-cerebellar network in younger but not in middle-aged or older adults. Our results indicate that the decrease of HRV with age is accompanied by changes in functional connectivity along the cortical midline. This extends our knowledge of brain-body interactions and their changes over the lifespan.
Assuntos
Envelhecimento/fisiologia , Encéfalo/fisiologia , Frequência Cardíaca/fisiologia , Rede Nervosa/fisiologia , Adulto , Fatores Etários , Idoso , Mapeamento Encefálico/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Inflammatory bowel diseases are autoimmune systemic forms of pathology. The concept of continuous life-long drug intake is a cornerstone in their therapy. The review presents the factors that reduce patients adherence to treatment and ways to improve it. They include informing the patient about the disease and treatment, selection of individual therapy regimen, consolidation of achievements, provision of social support and interaction with other specialists.
Assuntos
Doenças Inflamatórias Intestinais , Humanos , Doenças Inflamatórias Intestinais/terapia , Cooperação do PacienteRESUMO
Oestrogen rapidly enhances fast excitatory postsynaptic potentials, facilitates long-term potentiation (LTP) and increases spine numbers. Each effect likely contributes to the influence of the steroid on cognition and memory. In the present review, we first describe a model for the substrates of LTP that includes an outline of the synaptic events occurring during induction, expression and consolidation. Briefly, critical signalling pathways involving the small GTPases RhoA and Rac/Cdc42 are activated by theta burst-induced calcium influx and initiate actin filament assembly via phosphorylation (inactivation) of cofilin. Reorganisation of the actin cytoskeleton changes spine and synapse morphology, resulting in increased concentrations of AMPA receptors at stimulated contacts. We then use the synaptic model to develop a specific hypothesis about how oestrogen affects both baseline transmission and plasticity. Brief infusions of 17ß-oestradiol (E2 ) reversibly stimulate the RhoA, cofilin phosphorylation and actin polymerisation cascade of the LTP machinery; blocking this eliminates the effects of the steroid on transmission. We accordingly propose that E2 induces a weak form of LTP and thereby increases synaptic responses, a hypothesis that also accounts for how it markedly enhances theta burst induced potentiation. Although the effects of E2 on the cytoskeleton could be a result of the direct activation of small GTPases by oestrogen receptors on the synaptic membrane, the hormone also activates tropomyosin-related kinase B receptors for brain-derived neurotrophic factor, a neurotrophin that engages the RhoA-cofilin sequence and promotes LTP. The latter observations raise the possibility that E2 produces its effects on synaptic physiology via transactivation of neighbouring receptors that have prominent roles in the management of spine actin, synaptic physiology and plasticity.
Assuntos
Actinas/metabolismo , Estrogênios/fisiologia , Potenciação de Longa Duração/fisiologia , Plasticidade Neuronal/fisiologia , Transdução de Sinais/fisiologia , Sinapses/metabolismo , AnimaisRESUMO
Estrogen's acute, facilitatory effects on glutamatergic transmission and long-term potentiation (LTP) provide a potential explanation for the steroid's considerable influence on behavior. Recent work has identified mechanisms underlying these synaptic actions. Brief infusion of 17ß-estradiol (E2) into adult male rat hippocampal slices triggers actin polymerization within dendritic spines via a signaling cascade beginning with the GTPase RhoA and ending with inactivation of the filament-severing protein cofilin. Blocking this sequence, or actin polymerization itself, eliminates E2's effects on synaptic physiology. Notably, the theta burst stimulation used to induce LTP activates the same signaling pathway as E2 plus events that stabilize the reorganization of the sub-synaptic cytoskeleton. These observations suggest that E2 elicits a partial form of LTP, resulting in an increase of fast excitatory postsynaptic potentials (EPSPs) and a reduction in the threshold for lasting synaptic changes. While E2's effects on the cytoskeleton could be direct, results described here indicate that the hormone activates synaptic tropomyosin-related kinase B (TrkB) receptors for brain-derived neurotrophic factor (BDNF), a releasable neurotrophin that stimulates the RhoA to cofilin pathway. It is therefore possible that E2 acts via transactivation of neighboring receptors to modify the composition and structure of excitatory contacts. Finally, there is the question of whether a loss of acute synaptic actions contributes to the memory problems associated with estrogen depletion. Initial tests found that ovariectomy in middle-aged rats disrupts RhoA signaling, actin polymerization, and LTP consolidation. Acute applications of E2 reversed these defects, a result consistent with the idea that disturbances to actin management are one cause of behavioral effects that emerge with reductions in steroid levels.
Assuntos
Citoesqueleto/metabolismo , Estrogênios/metabolismo , Aprendizagem/fisiologia , Plasticidade Neuronal/fisiologia , Sinapses/metabolismo , Transmissão Sináptica/fisiologia , Animais , HumanosRESUMO
Stress is ubiquitous in modern life and exerts profound effects on cognitive and emotional functions. Thus, whereas acute stress enhances memory, longer episodes exert negative effects through as yet unresolved mechanisms. We report a novel, hippocampus-intrinsic mechanism for the selective memory defects that are provoked by stress. CRH (corticotropin-releasing hormone), a peptide released from hippocampal neurons during stress, depressed synaptic transmission, blocked activity-induced polymerization of spine actin and impaired synaptic plasticity in adult hippocampal slices. Live, multiphoton imaging demonstrated a selective vulnerability of thin dendritic spines to this stress hormone, resulting in depletion of small, potentiation-ready excitatory synapses. The underlying molecular mechanisms required activation and signaling of the actin-regulating small GTPase, RhoA. These results implicate the selective loss of dendritic spine sub-populations as a novel structural and functional foundation for the clinically important effects of stress on cognitive and emotional processes.
Assuntos
Hormônio Liberador da Corticotropina/fisiologia , Espinhas Dendríticas/ultraestrutura , Plasticidade Neuronal/fisiologia , Proteína rhoA de Ligação ao GTP/fisiologia , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/análogos & derivados , 1-(5-Isoquinolinasulfonil)-2-Metilpiperazina/farmacologia , Actinas/metabolismo , Animais , Hormônio Liberador da Corticotropina/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Potenciais Pós-Sinápticos Excitadores/fisiologia , Hipocampo/efeitos dos fármacos , Hipocampo/enzimologia , Hipocampo/fisiologia , Humanos , Masculino , Camundongos , Inibidores de Proteínas Quinases/farmacologia , Ratos , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinapses/ultraestrutura , Transmissão Sináptica/efeitos dos fármacos , Transmissão Sináptica/fisiologia , Proteína rhoA de Ligação ao GTP/metabolismoRESUMO
The Reelin-signaling pathway regulates neuronal positioning during embryonic development. Reelin, the extracellular matrix protein missing in reeler mutants, is secreted by neurons in laminae I, II and V, binds to Vldl and Apoer2 receptors on nearby neurons, and tyrosine phosphorylates the adaptor protein Disabled-1 (Dab1), which activates downstream signaling. We previously reported that reeler and dab1 mutants had significantly reduced mechanical and increased heat nociception. Here we extend our analysis to chemical, visceral, and cold pain and importantly, used Fos expression to relate positioning errors in mutant mouse dorsal horn to changes in neuronal activity. We found that noxious mechanical stimulation-induced Fos expression is reduced in reeler and dab1 laminae I-II, compared to wild-type mice. Additionally, mutants had fewer Fos-immunoreactive neurons in the lateral-reticulated area of the deep dorsal horn than wild-type mice, a finding that correlates with a 50% reduction and subsequent mispositioning of the large Dab1-positive cells in the mutant lateral-reticulated area. Furthermore, several of these Dab1 cells expressed Fos in wild-type mice but rarely in reeler mutants. By contrast, paralleling the behavioral observations, noxious heat stimulation evoked significantly greater Fos expression in laminae I-II of reeler and dab1 mutants. We then used the formalin test to show that chemical nociception is reduced in reeler and dab1 mutants and that there is a corresponding decrease in formalin-induced Fos expression. Finally, neither visceral pain nor cold-pain sensitivity differed between wild-type and mutant mice. As differences in the nociceptor distribution within reeler and dab1 mutant dorsal horn were not detected, these differential effects observed on distinct pain modalities suggest that dorsal horn circuits are organized along modality-specific lines.
Assuntos
Moléculas de Adesão Celular Neuronais/fisiologia , Proteínas da Matriz Extracelular/fisiologia , Proteínas do Tecido Nervoso/fisiologia , Nociceptividade/fisiologia , Serina Endopeptidases/fisiologia , Transdução de Sinais/fisiologia , Sensação Térmica/fisiologia , Percepção do Tato/fisiologia , Animais , Mapeamento Encefálico , Moléculas de Adesão Celular Neuronais/genética , Células Quimiorreceptoras/fisiologia , Temperatura Baixa , Proteínas da Matriz Extracelular/genética , Formaldeído , Expressão Gênica/fisiologia , Genes fos/genética , Temperatura Alta , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Knockout , Proteínas do Tecido Nervoso/genética , Nociceptores/fisiologia , Medição da Dor/efeitos dos fármacos , Estimulação Física , Proteína Reelina , Serina Endopeptidases/genética , Transdução de Sinais/genética , Sensação Térmica/genética , Percepção do Tato/genéticaRESUMO
The purpose of this study was to assess the epidemiology and some of the possible risk factors causing oral cleft in Tehran. The study was a 7-year retrospective study from March 1998 to March 2005. Twenty-five live births with cleft lip and/or palate (CL+/-P) were born between 20 March 1998 and 20 March 2005 from the total of 11,651 live births in a maternity hospital in Tehran. After recognizing the child as a cleft patient, previous and following children born were recognized as a noncleft sample. Cleft and noncleft samples were compared for variables such as gender, mother's age, parity, consanguineous marriage and infant's weight, and then analyzed with Chi-square. The overall incidence was 2.14 per 1000 live births. CL+ P is more prevalent, which was 52% and the least incidence was for "only cleft lip'' patients, which was 12%. This study reveals that the incidence of oral clefts in Tehran is higher than many other countries. Consanguineous marriage and low birth weight in cleft group were significant statistically from those of noncleft group.
Assuntos
Fenda Labial/epidemiologia , Fissura Palatina/epidemiologia , Peso ao Nascer , Consanguinidade , Estudos Epidemiológicos , Feminino , Humanos , Incidência , Recém-Nascido de Baixo Peso , Recém-Nascido , Irã (Geográfico)/epidemiologia , Masculino , Idade Materna , Paridade , Gravidez , Estudos Retrospectivos , Fatores de Risco , Fatores SexuaisRESUMO
It is shown that during the propagation of surface plasmon polariton (SPP) on a metal-coated tip of an optical fiber its wavelength essentially decreases and wave fields anomalously increase. Dependence of a degree of localization of SPP on sharpness of the structure and width of the metal layer is defined. The received results can be used to increase the resolution of scanning optical microscope.
RESUMO
Mutations in reeler, the gene coding for the Reelin protein, result in pronounced motor deficits associated with positioning errors (i.e. ectopic locations) in the cerebral and cerebellar cortices. In this study we provide the first evidence that the reeler mutant also has profound sensory defects. We focused on the dorsal horn of the spinal cord, which receives inputs from small diameter primary afferents and processes information about noxious, painful stimulation. We used immunocytochemistry to map the distribution of Reelin and Disabled-1 (the protein product of the reeler gene, and the intracellular adaptor protein, Dab1, involved in its signaling pathway) in adjacent regions of the developing dorsal horn, from early to late embryonic development. As high levels of Dab1 accumulate in cells that sustain positioning errors in reeler mutants, our findings of increased Dab1 immunoreactivity in reeler laminae I-III, lamina V and the lateral spinal nucleus suggest that there are incorrectly located neurons in the reeler dorsal horn. Subsequently, we identified an aberrant neuronal compaction in reeler lamina I and a reduction of neurons in the lateral spinal nucleus throughout the spinal cord. Additionally, we detected neurokinin-1 receptors expressed by Dab1-labeled neurons in reeler laminae I-III and the lateral spinal nucleus. Consistent with these anatomical abnormalities having functional consequences, we found a significant reduction in mechanical sensitivity and a pronounced thermal hyperalgesia (increased pain sensitivity) in reeler compared with control mice. As the nociceptors in control and reeler dorsal root ganglia are similar, our results indicate that Reelin signaling is an essential contributor to the normal development of central circuits that underlie nociceptive processing and pain.
Assuntos
Moléculas de Adesão Celular Neuronais/deficiência , Proteínas da Matriz Extracelular/deficiência , Regulação da Expressão Gênica no Desenvolvimento/fisiologia , Proteínas do Tecido Nervoso/deficiência , Células do Corno Posterior/fisiologia , Receptores Opioides/fisiologia , Serina Endopeptidases/deficiência , Medula Espinal/citologia , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Animais Recém-Nascidos , Comportamento Animal , Contagem de Células/métodos , Embrião de Mamíferos , Humanos , Imuno-Histoquímica/métodos , Masculino , Camundongos , Camundongos Mutantes Neurológicos , Proteínas do Tecido Nervoso/metabolismo , Medição da Dor/métodos , Receptores da Neurocinina-1/metabolismo , Proteína Reelina , Fatores Sexuais , Medula Espinal/enzimologia , Medula Espinal/crescimento & desenvolvimento , Receptor de NociceptinaRESUMO
The water distribution system (WDS) rehabilitation problem is defined here as a multi-objective optimisation problem under uncertainty. Two alternative problem formulations are considered. The first objective in both approaches is to minimise the total rehabilitation cost. The second objective is to either maximise the overall WDS robustness or to minimise the total WDS risk. The WDS robustness is defined as the probability of simultaneously satisfying minimum pressure head constraints at all nodes in the network. Total risk is defined as the sum of nodal risks, where nodal risk is defined as the product of the probability of pressure failure at that node and consequence of such failure. Decision variables are the alternative rehabilitation options for each pipe in the network. The only source of uncertainty is the future water consumption. Uncertain demands are modelled using any probability density functions (PDFs) assigned in the problem formulation phase. The corresponding PDFs of the analysed nodal heads are calculated using the Latin Hypercube sampling technique. The optimal rehabilitation problem is solved using the newly developed rNSGAII method which is a modification of the well-known NSGAII optimisation algorithm. In rNSGAII a small number of demand samples are used for each fitness evaluation leading to significant computational savings when compared to the full sampling approach. The two alternative approaches are tested, verified and their performance compared on the New York tunnels case study. The results obtained demonstrate that both new methodologies are capable of identifying the robust (near) Pareto optimal fronts while making significant computational savings.
Assuntos
Modelos Teóricos , Abastecimento de Água , Arquitetura de Instituições de Saúde , Medição de Risco , IncertezaRESUMO
OBJECTIVE: To determine the effect of hypertensive disorders in pregnancy on the neonatal outcome of growth restricted fetuses. There is conflicting data on the effect of hypertension during pregnancy on the incidence of neonatal respiratory distress syndrome (RDS) and intraventricular hemorrhage. Some studies report a lower incidence of RDS and intraventricular hemorrhage in infants of hypertensive mothers, whereas other studies report a similar or higher incidence in infants born to hypertensive mothers. STUDY DESIGN: We performed a retrospective analysis of 220 growth restricted fetuses born between January 1, 1996 to July 1, 1997 at the Department of Obstetrics and Gynecology of the University-Hospital at Homburg/Saar. Data were obtained by review of the medical records. Growth restricted infants born to preeclamptic women or women with HELLP syndrome were compared to growth restricted fetuses born to mothers without hypertensive disorders. RESULTS: Growth restricted fetuses born to hypertensive mothers had a significant lower birth weight (p < 0.05). The incidence of RDS in children born to hypertensive mothers was significantly higher (p < 0.05, p < 0.01) and they stayed significantly longer in the neonatal intensive care unit (p < 0.01). In contrast to infants born to mothers with HELLP syndrome (n = 7) there was no difference in the incidence of intraventricular hemorrhage, infection, sepsis, necrotizing enterocolitis or cardiac complications (arrhythmia, insufficiency) in case of preeclampsia (n = 68). The perinatal mortality of infants born to hypertensive mothers was significantly higher (p < 0.05, p < 0.01). CONCLUSION: This study does not support the contention that hypertensive disorders in pregnancy have a beneficial effect on the postnatal course of IUGR infants.
Assuntos
Hemorragia Cerebral/diagnóstico , Ventrículos Cerebrais , Síndrome HELLP/diagnóstico , Pré-Eclâmpsia/diagnóstico , Síndrome do Desconforto Respiratório do Recém-Nascido/diagnóstico , Adulto , Índice de Apgar , Causas de Morte , Hemorragia Cerebral/mortalidade , Feminino , Síndrome HELLP/mortalidade , Humanos , Recém-Nascido , Masculino , Pré-Eclâmpsia/mortalidade , Gravidez , Resultado da Gravidez , Síndrome do Desconforto Respiratório do Recém-Nascido/mortalidade , Estudos Retrospectivos , Fatores de Risco , Taxa de SobrevidaRESUMO
In order to investigate the systemic and central haemodynamics, blood perfusion, and metabolism of the myocardium in acute myocardial infarction (AMI), experiments were carried out in 80 mongrel dogs with experimental AMI, induced by ligation of the descending branch of the left coronary artery, and 183 patients with transmural AMI were clinically followed-up. It was found that after coronary artery ligation the blood flow in the intact myocardial parts increased, whereas in the infarcted zone it decreased. These shifts persisted fairly long after the induction of AMI. Simultaneously the cardiac output markedly tended to decrease in all animals, and this tendency also persisted for the next two days. It was proved that the haemodynamic shifts in question were associated with a decrease in the myocardial biosynthesis of individual fractions of RNA after the coronary artery ligation. The clinical observations confirmed that AMI was accompanied by a decrease in myocardial contractility. The degree of the decrease was directly proportional to the infarct size. The dependence of the changes on the localization of AMI was less marked.