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1.
Arthroscopy ; 40(3): 692-698, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-37532162

RESUMO

PURPOSE: To compare the 30-day outcomes, including length of stay, short-term complications, hospital readmission, all-cause reoperation, and death after arthroscopic Bankart (AB) and Latarjet. METHODS: Patients in the National Surgical Quality Improvement Program database who had undergone either AB or Latarjet-Bristow (LB) procedures for anterior shoulder instability from 2012 to 2018 were identified using Current Procedural Terminology codes. Nearest neighbor propensity score matching was used to address any potential demographic differences. The 30-day incidence of postoperative complications were compared, and univariate and multivariate logistic regressions were used to identify risk factors associated with the incidence of post-operative complications. RESULTS: A total of 7,519 patients were identified, with 6,990 (93.0%) undergoing AB and 529 (7.0%) LB. After propensity score matching, the baseline demographics were not significantly different (P > .05). There was no significant difference in rate of total adverse events between the AB and LB cohorts (P = .06). There was a significant difference in the rate of return to the operating room between LB (1.9%) when compared to AB (0%) (P < .001). Of reoperations, 40% were due to need for revision stabilization (0.8% of all LB cases) and 40% were for irrigation and debridement. There was also a significant difference in operative time (AB = 87 minutes, LB = 131 minutes; P < .0001). CONCLUSIONS: Overall 30-day complication rates were low for both groups, with similar rates among AB and LB patients. However, there was a statistically significant increased rate of short-term reoperation or revision stabilization in the LB cohort. LEVEL OF EVIDENCE: Level III, retrospective comparative prognostic trial.


Assuntos
Instabilidade Articular , Luxação do Ombro , Articulação do Ombro , Humanos , Artroscopia/métodos , Instabilidade Articular/cirurgia , Complicações Pós-Operatórias/etiologia , Pontuação de Propensão , Recidiva , Reoperação , Estudos Retrospectivos , Ombro , Luxação do Ombro/cirurgia , Articulação do Ombro/cirurgia
2.
Artigo em Inglês | MEDLINE | ID: mdl-39123065

RESUMO

INTRODUCTION: This is a retrospective cohort study designed to compare short-term postoperative complication rates between closed humeral shaft fractures treated by open reduction and internal fixation (ORIF) versus intramedullary nailing (IMN), as well as secondary independent risk factors for adverse outcomes. MATERIALS AND METHODS: The American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database was queried using CPT codes to identify patients that underwent an open reduction and plate fixation or intramedullary nailing procedure for a closed humeral shaft fracture from 2010 to 2021. Cohorts were matched using propensity scores to account for demographic differences and rates of complications were compared between the two groups. RESULTS: From the database, a total of 4,222 patients were identified who met inclusion criteria, with 3,326 and 896 undergoing ORIF and IMN respectively. After propensity score matching, 866 of the nearest-neighbor matches were included in each cohort for a total of 1,732 patients in the final analysis. The rate of any adverse event (AAE) was significantly higher in the ORIF cohort (16.3%) than the IMN cohort (12.1%, p = 0.01). The ORIF group had higher rates of postoperative transfusion (p = 0.002), return to OR (p = 0.005), and surgical site infection (SSI, p = 0.03). After multivariate analysis, ASA class 4, increasing age, increasing operative time, and history of bleeding disorder were found to increase the risk of AAE in both ORIF and IMN patients. CONCLUSIONS: While prior studies have claimed higher complication rates in IMN patients, this study found a significantly higher short-term risk of AAE in ORIF patients when compared in matched cohorts. However, individual 30-day complication rates do not differ significantly between procedures, and both have been shown to be safe and effective tools in the management of humeral shaft fractures.

3.
Arthroscopy ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-38000486

RESUMO

PURPOSE: To determine what patient or surgical factors are associated with an increased risk of arthrofibrosis requiring manipulation under anesthesia (MUA) or lysis of adhesions (LOA) after anterior cruciate ligament reconstruction (ACLR). METHODS: A systematic review was performed in adherence to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Cochrane, Embase, and Medline databases were searched for studies published through February 2023. Inclusion criteria were studies that identified risk factors for MUA and/or LOA after ACLR. Studies investigating arthrofibrosis after multiligamentous knee injuries or ACL repair were excluded. RESULTS: Eleven studies including a total of 333,876 ACLRs with 4,842 subsequent MUA or LOA (1.45%) were analyzed. Increasing age was associated with an increased risk in 3 studies (P < .001, P < .05, P < .01) but was found to have no association another two. Other factors that were identified by multiple studies as risk factors for MUA/LOA were female sex (4 studies), earlier surgery (5 studies), use of anticoagulants other than aspirin (2 studies), and concomitant meniscal repair (4 studies). CONCLUSIONS: In total, 1.45% of the patients who underwent ACLR and were included in this systematic review had to undergo a subsequent MUA/LOA to treat arthrofibrosis. Female sex, older age, earlier surgery, use of anticoagulants other than aspirin, and concomitant meniscal repair were associated with increased risk of MUA/LOA. The modifiable risks, including use of anticoagulants and time between injury and surgery, can be considered when making treatment decisions. LEVEL OF EVIDENCE: Level IV, systematic review of Level III/IV evidence.

4.
Am J Emerg Med ; 56: 310-311, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-34602332

RESUMO

As part of an institutional effort to develop an atmosphere of communication and encourage mutual appreciation of respective viewpoints, we used a cross-sectional survey to investigate the perceptions of emergency (EM) and internal medicine (IM) residents and faculty, particularly, their attitudes about collaboration, mutual respect, and mistreatment. This cross-sectional survey was administered to the EM and IM faculty and residents of a county, academic hospital with a Level 1 Trauma Center to evaluate each specialty's current perception of professional behavior and observations of unprofessional behavior in order to identify areas for improvement. The survey items were answered using a 5-point Likert scale and was analyzed using the unpaired t-test. A total of 68 residents and faculty completed the survey, 32 (59.4% residents) from EM and 36 (94.4% residents) from IM. Among all EM and IM clinicians, 48.6% felt that there was a culture of clinical collaboration. Approximately half of the respondents (51.5%) felt that the state of professionalism between the two departments was below that of other departments. About 10% (11.8%) of all respondents reported experiencing unprofessional behaviors from the other department at least once a month. Challenges identified by EM faculty and residents included time to consult, recommendations, and disposition. Challenges identified by IM included difficulty contacting EM providers and lack of communication regarding patient's clinical status changes. Both specialties emphasized the importance of improved patient care transitional processes. This study is an important first look at the prevalence of negative attitudes and misperceptions between EM and IM providers. These perspectives can occur due to breakdown of communication and differing expectations. Such asynchronies can cause a toxic workplace environment, diminished performance, and poor patient outcomes.


Assuntos
Medicina de Emergência , Internato e Residência , Médicos , Comunicação , Estudos Transversais , Medicina de Emergência/educação , Humanos , Inquéritos e Questionários
5.
J Stroke Cerebrovasc Dis ; 31(8): 106546, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35576861

RESUMO

OBJECTIVE: To examine potential genetic relationships between migraine and the two distinct phenotypes posterior circulation ischemic stroke (PCiS) and anterior circulation ischemic stroke (ACiS), we generated migraine polygenic risk scores (PRSs) and compared these between PCiS and ACiS, and separately vs. non-stroke control subjects. METHODS: Acute ischemic stroke cases were classified as PCiS or ACiS based on lesion location on diffusion-weighted MRI. Exclusion criteria were lesions in both vascular territories or uncertain territory; supratentorial PCiS with ipsilateral fetal posterior cerebral artery; and cases with atrial fibrillation. We generated migraine PRS for three migraine phenotypes (any migraine; migraine without aura; migraine with aura) using publicly available GWAS data and compared mean PRSs separately for PCiS and ACiS vs. non-stroke control subjects, and between each stroke phenotype. RESULTS: Our primary analyses included 464 PCiS and 1079 ACiS patients with genetic European ancestry. Compared to non-stroke control subjects (n=15396), PRSs of any migraine were associated with increased risk of PCiS (p=0.01-0.03) and decreased risk of ACiS (p=0.010-0.039). Migraine without aura PRSs were significantly associated with PCiS (p=0.008-0.028), but not with ACiS. When comparing PCiS vs. ACiS directly, migraine PRSs were higher in PCiS vs. ACiS for any migraine (p=0.001-0.010) and migraine without aura (p=0.032-0.048). Migraine with aura PRS did not show a differential association in our analyses. CONCLUSIONS: Our results suggest a stronger genetic overlap between unspecified migraine and migraine without aura with PCiS compared to ACiS. Possible shared mechanisms include dysregulation of cerebral vessel endothelial function.


Assuntos
AVC Isquêmico , Enxaqueca com Aura , Enxaqueca sem Aura , Imagem de Difusão por Ressonância Magnética , Humanos , Enxaqueca com Aura/diagnóstico por imagem , Enxaqueca com Aura/genética , Enxaqueca sem Aura/diagnóstico por imagem , Enxaqueca sem Aura/genética , Fatores de Risco
6.
Clin Gerontol ; : 1-11, 2022 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-35426768

RESUMO

OBJECTIVES: In geriatric psychiatry Autism Spectrum Disorders (ASD) are increasingly recognized. This study explores what clinicians know about diagnostic and/or therapeutic aspects of autistic older adults and how aging plays a role in the course of ASD. METHODS: A Delphi study outlines the point of view of 11 clinical experts in the Netherlands and Belgium (Flanders). RESULTS: Regarding diagnostics, age-specific aspects need to be considered. Age-related characteristics (cognitive differences, life events, co-occurring conditions) influence detecting autistic features in older adults. Regarding treatment, counseling methods need to be adapted. Psychoeducation, family therapy, couples therapy, behavioral counseling and psychopharmaca can be helpful in meeting the needs of autistic older adults. There was no consensus on the effects of aging on autistic older adults. CONCLUSIONS: Diagnosis and treatment of ASD need adaptation for autistic older adults. Further research is needed on the validation of measurement tools, recorded treatment, therapy, psychoeducation, and the effects of aging among people on the autism spectrum. CLINICAL IMPLICATIONS: Available knowledge helps clinicians to detect ASD in older adults and adapt to the specific features and needs of autistic older adults. The effects of aging on the course of ASD are unclear yet.

7.
Eur J Neurol ; 28(2): 401-410, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33065757

RESUMO

BACKGROUND AND PURPOSE: Cognitive impairment is a common sequel of recent small subcortical infarction (RSSI) and might be negatively affected by preexisting cerebral small vessel disease (SVD). We investigated whether the course of cognitive function in patients with RSSI is influenced by the severity of white matter hyperintensities (WMH), an important imaging feature of SVD. METHODS: Patients with magnetic resonance imaging (MRI)-proven single RSSI were tested neuropsychologically concerning global cognition, processing speed, attention, and set-shifting. Deep and periventricular WMH severity was assessed using the Fazekas scale, and total WMH lesion volume was calculated from T1-weighted MRI images. We compared baseline function and course of cognition 15 months after the acute event in patients with absent, mild, and moderate-to-severe WMH. RESULTS: The study cohort comprised 82 RSSI patients (mean age: 61 ± 10 years, 23% female). At baseline, 40% had cognitive impairment (1.5 standard deviations below standardized mean), and deficits persisted in one-third of the sample after 15 months. After age correction, there were no significant differences in set-shifting between WMH groups at baseline. However, although patients without WMH (deep: p < 0.001, periventricular: p = 0.067) or only mild WMH (deep: p = 0.098, periventricular: p = 0.001) improved in set-shifting after 15 months, there was no improvement in patients with moderate-to-severe WMH (deep: p = 0.980, periventricular: p = 0.816). Baseline total WMH volume (p = 0.002) was the only significant predictor for attention 15 months poststroke. CONCLUSIONS: This longitudinal study demonstrates that preexisting moderate-to-severe WMH negatively affect the restoration of cognitive function after RSSI, suggesting limited functional reserve in patients with preexisting SVD.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Disfunção Cognitiva , Acidente Vascular Cerebral , Substância Branca , Idoso , Doenças de Pequenos Vasos Cerebrais/complicações , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Cognição , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Feminino , Humanos , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Substância Branca/diagnóstico por imagem
8.
J Appl Microbiol ; 131(4): 1564-1577, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33825272

RESUMO

AIMS: Recent foodborne disease outbreaks have caused farmers to re-evaluate their practices. In particular, concern that soil amendments could introduce foodborne pathogens onto farms and promote their survival in soils has led farmers to reduce or eliminate the application of animal-based composts. However, organic amendments (such as composts and cover crops) could bolster food safety by increasing soil microbial diversity and activity, which can act as competitors or antagonists and reduce pathogen survival. METHODS AND RESULTS: Leveraging a study of a 27-year experiment comparing organic and conventional soil management, we evaluate the impacts of composted poultry litter and cover crops on soil chemistry, bacterial communities and survival of Salmonella enterica and Listeria monocytogenes. We found that bacterial community composition strongly affected pathogen survival in soils. Specifically, organic soils managed with cover crops and composts hosted more macronutrients and bacterial communities that were better able to suppress Salmonella and Listeria. For example, after incubating soils for 10 days at 20°C, soils without composts retained fourfold to fivefold more Salmonella compared to compost-amended soils. However, treatment effects dissipated as bacterial communities converged over the growing season. CONCLUSIONS: Our results suggest that composts and cover crops may be used to build healthy soils without increasing foodborne pathogen survival. SIGNIFICANCE AND IMPACT OF THE STUDY: Our work suggests that animal-based composts do not promote pathogen survival and may even promote bacterial communities that suppress pathogens. Critically, proper composting techniques are known to reduce pathogen populations in biological soil amendments of animal origin, which can reduce the risks of introducing pathogens to farm fields in soil amendments. Thus, animal-based composts and cover crops may be a safe alternative to conventional fertilizers, both because of the known benefits of composts for soil health and because it may be possible to apply amendments in such a way that food-safety risks are mitigated rather than exacerbated.


Assuntos
Compostagem , Salmonella enterica , Animais , Fertilizantes , Esterco , Solo , Microbiologia do Solo
9.
Ann Oncol ; 31(3): 422-429, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32067684

RESUMO

BACKGROUND: Long-term survival of high-risk neuroblastoma patients is still below 50% despite intensive multimodal treatment. This trial aimed to address whether the addition of two topotecan-containing chemotherapy courses compared to standard induction therapy improves event-free survival (EFS) of these patients. PATIENTS AND METHODS: An open-label, multicenter, prospective randomized controlled trial was carried out at 58 hospitals in Germany and Switzerland. Patients aged 1-21 years with stage 4 neuroblastoma and patients aged 6 months to 21 years with MYCN-amplified tumors were eligible. The primary endpoint was EFS. Patients were randomly assigned to standard induction therapy with six chemotherapy courses or to experimental induction chemotherapy starting with two additional courses of topotecan, cyclophosphamide, and etoposide followed by standard induction chemotherapy (eight courses in total). After induction chemotherapy, all patients received high-dose chemotherapy with autologous hematopoietic stem cell rescue and isotretinoin for consolidation. Radiotherapy was applied to patients with active tumors at the end of induction chemotherapy. RESULTS: Of 536 patients enrolled in the trial, 422 were randomly assigned to the control arm (n = 211) and the experimental arm (n = 211); the median follow-up time was 3.32 years (interquartile range 1.65-5.92). At data lock, the 3-year EFS of experimental and control patients was 34% and 32% [95% confidence Interval (CI) 28% to 40% and 26% to 38%; P = 0.258], respectively. Similarly, the 3-year overall survival of the patients did not differ [54% and 48% (95% CI 46% to 62% and 40% to 56%), respectively; P = 0.558]. The response to induction chemotherapy was not different between the arms. The median number of non-fatal toxicities per patient was higher in the experimental group while the median number of toxicities per chemotherapy course was not different. CONCLUSION: While the burden for the patients was increased by prolonging the induction chemotherapy and the toxicity, the addition of two topotecan-containing chemotherapy courses did not improve the EFS of high-risk neuroblastoma patients and thus cannot be recommended. CLINICAL TRIALS. GOV NUMBER: NCT number 03042429.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Quimioterapia de Indução , Neuroblastoma , Adolescente , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Criança , Pré-Escolar , Intervalo Livre de Doença , Alemanha , Humanos , Lactente , Neuroblastoma/tratamento farmacológico , Estudos Prospectivos , Suíça , Resultado do Tratamento , Adulto Jovem
10.
Eur J Neurol ; 27(6): 928-943, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32056347

RESUMO

Alzheimer's disease (AD) is characterized by high heterogeneity in disease manifestation, progression and risk factors. High phenotypic variability is currently regarded as one of the largest hurdles in early diagnosis and in the design of clinical trials; there is therefore great interest in identifying factors driving variability that can be used for patient stratification. In addition to genetic and lifestyle factors, the individual's sex and gender are emerging as crucial drivers of phenotypic variability. Evidence exists on sex and gender differences in the rate of cognitive deterioration and brain atrophy, and in the effect of risk factors as well as in the patterns of diagnostic biomarkers. Such evidence might be of high relevance and requires attention in clinical practice and clinical trials. However, sex and gender differences are currently seldom appreciated; importantly, consideration of sex and gender differences is not currently a focus in the design and analysis of clinical trials for AD. The objective of this position paper is (i) to provide an overview of known sex and gender differences that might have implications for clinical practice, (ii) to identify the most important knowledge gaps in the field (with a special regard to clinical trials) and (iii) to provide conclusions for future studies. This scientific statement is endorsed by the European Academy of Neurology.


Assuntos
Doença de Alzheimer , Transtornos Cognitivos , Cognição , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/epidemiologia , Peptídeos beta-Amiloides , Biomarcadores , Ensaios Clínicos como Assunto , Humanos , Neurologia , Caracteres Sexuais , Proteínas tau
11.
Eur J Neurol ; 27(10): 1805-1820, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32713125

RESUMO

BACKGROUND AND PURPOSE: Dementia is one of the most common disorders and is associated with increased morbidity, mortality and decreased quality of life. The present guideline addresses important medical management issues including systematic medical follow-up, vascular risk factors in dementia, pain in dementia, use of antipsychotics in dementia and epilepsy in dementia. METHODS: A systematic review of the literature was carried out. Based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework, we developed a guideline. Where recommendations based on GRADE were not possible, a good practice statement was formulated. RESULTS: Systematic management of vascular risk factors should be performed in patients with mild to moderate dementia as prevention of cerebrovascular pathology may impact on the progression of dementia (Good Practice statement). Individuals with dementia (without previous stroke) and atrial fibrillation should be treated with anticoagulants (weak recommendation). Discontinuation of opioids should be considered in certain individuals with dementia (e.g. for whom there are no signs or symptoms of pain or no clear indication, or suspicion of side effects; Good Practice statement). Behavioral symptoms in persons with dementia should not be treated with mild analgesics (weak recommendation). In all patients with dementia treated with opioids, assessment of the individual risk-benefit ratio should be performed at regular intervals. Regular, preplanned medical follow-up should be offered to all patients with dementia. The setting will depend on the organization of local health services and should, as a minimum, include general practitioners with easy access to dementia specialists (Good Practice statement). Individuals with dementia and agitation and/or aggression should be treated with atypical antipsychotics only after all non-pharmacological measures have been proven to be without benefit or in the case of severe self-harm or harm to others (weak recommendation). Antipsychotics should be discontinued after cessation of behavioral disturbances and in patients in whom there are side effects (Good Practice statement). For treatment of epilepsy in individuals with dementia, newer anticonvulsants should be considered as first-line therapy (Good Practice statement). CONCLUSION: This GRADE-based guideline offers recommendations on several important medical issues in patients with dementia, and thus adds important guidance for clinicians. For some issues, very little or no evidence was identified, highlighting the importance of further studies within these areas.


Assuntos
Doença de Alzheimer , Demência , Neurologia , Academias e Institutos , Idoso , Analgésicos , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Dairy Sci ; 103(5): 4579-4587, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32147259

RESUMO

The first objective of this study was to determine whether differences would occur among teat end preparation techniques with regard to potential contamination of milk samples collected for bacterial culture. The second objective was to determine whether differences would be detected in genus or species of bacteria isolated from samples collected using the various methods as well as from contaminated or uncontaminated samples. Mammary quarter foremilk samples were collected from lactating dairy cattle at the University of Missouri Foremost Research Dairy Farm (Columbia). Four different teat end preparation methods were used to compare contamination rates in milk samples. Sampling techniques used before milk collection included (1) no preparation, (2) pre-milking disinfection and single-use towel drying of teats only, (3) scrubbing of the teat end with alcohol only, and (4) pre-milking disinfection, single-use towel drying, and scrubbing of the teat end with alcohol. Milk was plated on Columbia blood agar. Cultures were read at 48 h, with the number of morphologically different bacterial colony types quantified and isolated. Isolates were identified using MALDI-TOF mass spectrometry. Median numbers of colony types were compared among groups using Kruskal-Wallis ANOVA with post-hoc pairwise comparisons, and proportional data were compared using the chi-squared test. A total of 168 cows, including 665 quarters, were sampled, and 1,614 isolates resulted. Analysis with MALDI-TOF identified 29 unique genera and 81 unique species among the samples. More contaminated samples occurred in groups 1 and 2 compared with groups 3 and 4. Group 3 had more contaminated samples than group 4. The majority of Pseudomonas spp. isolates were identified within group 2. When applying previously described niches to Staphylococcus spp., environmental species were more likely to be identified among contaminated samples, whereas host-adapted species were more likely to be identified among uncontaminated samples. These data confirm that scrubbing the teat end with alcohol after pre-milking disinfection with an iodine-based teat disinfectant and drying of the teat minimizes contamination of the milk sample.


Assuntos
Bovinos/microbiologia , Desinfecção/métodos , Glândulas Mamárias Animais/microbiologia , Leite/microbiologia , Animais , Bactérias/classificação , Bactérias/isolamento & purificação , Desinfetantes , Feminino , Iodo , Lactação , Staphylococcus/isolamento & purificação
13.
Anaesthesist ; 69(2): 122-125, 2020 02.
Artigo em Alemão | MEDLINE | ID: mdl-32002562

RESUMO

This article presents the case of an accidental transdermal opioid intoxication in a paramedic. During an ambulance flight mission for patient repatriation several ampules containing opioids were broken unnoticed inside the ampule kit in the outside pocket of the work trousers of the paramedic. He developed the typical clinical picture of opioid intoxication with clouding of consciousness, miosis, and respiratory depression. This necessitated continuous monitoring of vital signs as well as repetitive administration of naloxone under the improvised circumstances of a mission abroad.


Assuntos
Analgésicos Opioides/intoxicação , Auxiliares de Emergência , Humanos , Masculino , Naloxona/uso terapêutico , Insuficiência Respiratória
14.
Artigo em Inglês | MEDLINE | ID: mdl-30373793

RESUMO

Nucleoside reverse transcriptase inhibitors (NRTI), such as zidovudine (AZT), are constituents of HIV-1 therapy and are used for the prevention of mother-to-child transmission. Prolonged thymidine analogue exposure has been associated with mitochondrial toxicities to heart, liver, and skeletal muscle. We hypothesized that the thymidine analogue AZT might interfere with autophagy in myocytes, a lysosomal degradation pathway implicated in the regulation of mitochondrial recycling, cell survival, and the pathogenesis of myodegenerative diseases. The impact of AZT and lamivudine (3TC) on C2C12 myocyte autophagy was studied using various methods based on LC3-green fluorescent protein overexpression or LC3 staining in combination with Western blotting, flow cytometry, and confocal and electron microscopy. Lysosomal and mitochondrial functions were studied using appropriate staining for lysosomal mass, acidity, cathepsin activity, as well as mitochondrial mass and membrane potential in combination with flow cytometry and confocal microscopy. AZT, but not 3TC, exerted a significant dose- and time-dependent inhibitory effect on late stages of autophagosome maturation, which was reversible upon mTOR inhibition. Inhibition of late autophagy at therapeutic drug concentrations led to dysfunctional mitochondrial accumulation with membrane hyperpolarization and increased reactive oxygen species (ROS) generation and, ultimately, compromised cell viability. These AZT effects could be readily replicated by pharmacological and genetic inhibition of myocyte autophagy and, most importantly, could be rescued by pharmacological stimulation of autophagolysosomal biogenesis. Our data suggest that the thymidine analogue AZT inhibits autophagy in myocytes, which in turn leads to the accumulation of dysfunctional mitochondria with increased ROS generation and compromised cell viability. This novel mechanism could contribute to our understanding of the long-term side effects of antiviral agents.


Assuntos
Autofagia/efeitos dos fármacos , Lamivudina/toxicidade , Mitocôndrias/patologia , Células Musculares/patologia , Inibidores da Transcriptase Reversa/toxicidade , Zidovudina/toxicidade , Fármacos Anti-HIV/farmacologia , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Espécies Reativas de Oxigênio/metabolismo
15.
Neuroradiology ; 61(6): 633-642, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30852630

RESUMO

PURPOSE: Through a European-wide survey, we assessed the current clinical practice of imaging in the primary evaluation of dementia, with respect to standardised imaging, evaluation and reporting. METHODS: An online questionnaire was emailed to all European Society of Neuroradiology (ESNR) members (n = 1662) and non-members who had expressed their interest in ESNR activities in the past (n = 6400). The questionnaire featured 42 individual items, divided into multiple choice, single best choice and free text answers. Information was gathered on the context of the practices, available and preferred imaging modalities, applied imaging protocols and standards for interpretation, reporting and communication. RESULTS: A total of 193 unique (non-duplicate) entries from the European academic and non-academic institutions were received from a total of 28 countries. Of these, 75% were neuroradiologists, 12% general radiologists and 11% (neuro) radiologists in training. Of responding centres, 38% performed more than five scans/week for suspected dementia. MRI was primarily used in 72% of centres. Over 90% of centres acquired a combination of T2w, FLAIR, T1w, DWI and T2*w sequences. Visual rating scales were used in 75% of centres, most often the Fazekas and medial temporal atrophy scale; 32% of respondents lacked full confidence in their use. Only 23% of centres performed volumetric analysis. A minority of centres (28%) used structured reports. CONCLUSIONS: Current practice in dementia imaging is fairly homogeneous across Europe, in terms of image acquisition and image interpretation. Hurdles identified include training on the use of visual rating scales, implementation of volumetric assessment and structured reporting.


Assuntos
Demência/diagnóstico por imagem , Neuroimagem/métodos , Padrões de Prática Médica/estatística & dados numéricos , Europa (Continente) , Humanos , Imageamento por Ressonância Magnética/estatística & dados numéricos , Sociedades Médicas , Inquéritos e Questionários
16.
Z Rheumatol ; 78(8): 743-752, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31468168

RESUMO

Rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis are the most common chronic autoimmune rheumatic diseases. For all three diseases an early diagnosis and initiation of treatment is crucial. The proof of concept network study "Rheuma-VOR" is a further developed version of the predecessor project ADAPTHERA and was extended to several federal states. The aim of this prospective study is to improve the early diagnosis of rheumatoid arthritis, psoriatic arthritis and axial spondylarthritis and thus positively impact the quality of care for patients with the help of multidisciplinary coordinating centers. To date 3710 disease-specific questionnaires from patients with the suspected diagnosis of rheumatoid arthritis, psoriatic arthritis or axial spondylarthritis from 1298 different primary care providers were registered in the multidisciplinary coordination centers. A total of 1958 appointments were made with 1 of the 53 participating rheumatology specialists. In 876 patients, 1 of the 3 rheumatic diseases was diagnosed in an early stage. The waiting period was on average 42.5 days depending on the federal state, which is well below the nationwide average. It should also be noted that the coordinated cooperation and risk stratification of the Rheuma-VOR coordination centers relieved the capacity of rheumatology specialists by 1281 appointments (34.5%). In addition, the 2­week Rheuma Bus Tour and the accompanying initiatives in Rhineland-Palatinate (Rheuma-VOR screening app and the triage consultation) are showing first promising positive results.


Assuntos
Prestação Integrada de Cuidados de Saúde/organização & administração , Doenças Reumáticas/diagnóstico , Reumatologia , Artrite Psoriásica/diagnóstico , Artrite Reumatoide/diagnóstico , Prestação Integrada de Cuidados de Saúde/normas , Diagnóstico Precoce , Humanos , Programas Nacionais de Saúde , Estudos Prospectivos , Reumatologia/organização & administração , Espondilartrite/diagnóstico
17.
Z Rheumatol ; 78(8): 722-742, 2019 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-31468170

RESUMO

In order to reduce the prognostically relevant time interval between the initial manifestation of a rheumatic and musculoskeletal disease and diagnosis as well as the consecutive initiation of an appropriate treatment, several rheumatological centers in Germany have improved the access to initial rheumatologic evaluation by establishing early recognition/screening clinics at their respective sites. Corresponding models located at Altoetting·Burghausen, Bad Pyrmont, Berlin Buch, Duesseldorf, Heidelberg, Herne, Mannheim as well as supraregional/multicenter initiatives Rheuma Rapid, RhePort and Rheuma-VOR are presented in this overview along with the respective characteristics, potential advantages and disadvantages, but also first evaluation results of several models. The aim of this publication is to promote early detection of rheumatic and musculoskeletal diseases as one of the most important challenges in current rheumatology by encouraging further rheumatologic centers and practices to launch their own early recognition/screening consultation model on the basis of aspects presented herein.


Assuntos
Doenças Musculoesqueléticas , Doenças Reumáticas , Reumatologia , Diagnóstico Precoce , Alemanha , Humanos , Doenças Musculoesqueléticas/diagnóstico , Doenças Musculoesqueléticas/terapia , Encaminhamento e Consulta , Doenças Reumáticas/diagnóstico , Doenças Reumáticas/terapia , Reumatologia/métodos
18.
Nonlinear Dynamics Psychol Life Sci ; 23(2): 199-228, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30898192

RESUMO

Previous research has found that spontaneous synchronization of bodily movements emerges when people interact. This dynamic interactional synchrony occurs in all kinds of everyday movements and has been demonstrated empirically in a variety of social contexts. The objective of this study is to advance our understanding of the dynamical processes that enable the spontaneous and fluid coordination of movements in more naturalistic social interactions. We measured the degree of interactional synchrony of 44 dyads who enacted a series of knock-knock jokes together and we manipulated the perceptual information available (using auditory occlusion) and the individuals' dynamical motor 'signatures' by weighting their limbs. Our analyses using relative phase and fractal/multifractal measures support the conclusion that both local and global dynamical synchronization processes sustain the interactional fluidity seen in conversational exchanges and provide an embodied foundation for how humans connect and cooperate socially.


Assuntos
Comunicação , Relações Interpessoais , Fractais , Humanos , Modelos Teóricos
19.
HIV Med ; 19(2): 90-101, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-28857427

RESUMO

OBJECTIVES: B-cell dysfunction and activation are thought to contribute to lymphoma development in HIV-positive people; however, the mechanisms are not well understood. We investigated levels of several markers of B-cell dysfunction [free light chain (FLC)-κ, FLC-λ, immunoglobulin G (IgG), IgA, IgM and IgD] prior to lymphoma diagnosis in HIV-positive people. METHODS: A nested matched case-control study was carried out within the EuroSIDA cohort, including 73 HIV-positive people with lymphoma and 143 HIV-positive lymphoma-free controls. Markers of B-cell dysfunction were measured in prospectively stored serial plasma samples collected before the diagnosis of lymphoma (or selection date in controls). Marker levels ≤ 2 and > 2 years prior to diagnosis were investigated. RESULTS: Two-fold higher levels of FLC-κ [odds ratio (OR) 1.84; 95% confidence interval (CI) 1.19, 2.84], FLC-λ (OR 2.15; 95% CI 1.34, 3.46), IgG (OR 3.05; 95% CI 1.41, 6.59) and IgM (OR 1.46; 95% CI 1.01, 2.11) were associated with increased risk of lymphoma > 2 years prior to diagnosis, but not ≤ 2 years prior. Despite significant associations > 2 years prior to diagnosis, the predictive accuracy of each marker was poor, with FLC-λ emerging as the strongest candidate with a c-statistic of 0.67 (95% CI 0.58, 0.76). CONCLUSIONS: FLC-κ, FLC-λ and IgG levels were higher > 2 years before lymphoma diagnosis, suggesting that B-cell dysfunction occurs many years prior to lymphoma development. However, the predictive value of each marker was low and they are unlikely candidates for risk assessment for targeted intervention.


Assuntos
Linfócitos B/imunologia , Linfócitos B/patologia , Infecções por HIV/complicações , Ativação Linfocitária , Linfoma/patologia , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Imunoglobulina G/sangue , Cadeias Leves de Imunoglobulina/sangue , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
20.
Phys Rev Lett ; 120(8): 083401, 2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29543028

RESUMO

We report spectroscopic observation of Rydberg polarons in an atomic Bose gas. Polarons are created by excitation of Rydberg atoms as impurities in a strontium Bose-Einstein condensate. They are distinguished from previously studied polarons by macroscopic occupation of bound molecular states that arise from scattering of the weakly bound Rydberg electron from ground-state atoms. The absence of a p-wave resonance in the low-energy electron-atom scattering in Sr introduces a universal behavior in the Rydberg spectral line shape and in scaling of the spectral width (narrowing) with the Rydberg principal quantum number, n. Spectral features are described with a functional determinant approach (FDA) that solves an extended Fröhlich Hamiltonian for a mobile impurity in a Bose gas. Excited states of polyatomic Rydberg molecules (trimers, tetrameters, and pentamers) are experimentally resolved and accurately reproduced with a FDA.

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