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1.
Brain Pathol ; 34(1): e13200, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581289

RESUMO

Myelin protein zero (MPZ/P0) is a major structural protein of peripheral nerve myelin. Disease-associated variants in the MPZ gene cause a wide phenotypic spectrum of inherited peripheral neuropathies. Previous nerve biopsy studies showed evidence for subtype-specific morphological features. Here, we aimed at enhancing the understanding of these subtype-specific features and pathophysiological aspects of MPZ neuropathies. We examined archival material from two Central European centers and systematically determined genetic, clinical, and neuropathological features of 21 patients with MPZ mutations compared to 16 controls. Cases were grouped based on nerve conduction data into congenital hypomyelinating neuropathy (CHN; n = 2), demyelinating Charcot-Marie-Tooth (CMT type 1; n = 11), intermediate (CMTi; n = 3), and axonal CMT (type 2; n = 5). Six cases had combined muscle and nerve biopsies and one underwent autopsy. We detected four MPZ gene variants not previously described in patients with neuropathy. Light and electron microscopy of nerve biopsies confirmed fewer myelinated fibers, more onion bulbs and reduced regeneration in demyelinating CMT1 compared to CMT2/CMTi. In addition, we observed significantly more denervated Schwann cells, more collagen pockets, fewer unmyelinated axons per Schwann cell unit and a higher density of Schwann cell nuclei in CMT1 compared to CMT2/CMTi. CHN was characterized by basal lamina onion bulb formation, a further increase in Schwann cell density and hypomyelination. Most late onset axonal neuropathy patients showed microangiopathy. In the autopsy case, we observed prominent neuromatous hyperinnervation of the spinal meninges. In four of the six muscle biopsies, we found marked structural mitochondrial abnormalities. These results show that MPZ alterations not only affect myelinated nerve fibers, leading to either primarily demyelinating or axonal changes, but also affect non-myelinated nerve fibers. The autopsy case offers insight into spinal nerve root pathology in MPZ neuropathy. Finally, our data suggest a peculiar association of MPZ mutations with mitochondrial alterations in muscle.


Assuntos
Doença de Charcot-Marie-Tooth , Proteína P0 da Mielina , Humanos , Proteína P0 da Mielina/genética , Doença de Charcot-Marie-Tooth/genética , Doença de Charcot-Marie-Tooth/patologia , Mutação/genética , Proteínas/genética , Biópsia
2.
Science ; 379(6634): 815-820, 2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36821693

RESUMO

Pyrocumulonimbus (pyroCb) are wildfire-generated convective clouds that can inject smoke directly into the stratosphere. PyroCb have been tracked for years, yet their apparent rarity and episodic nature lead to highly uncertain climate impacts. In situ measurements of pyroCb smoke reveal its distinctive and exceptionally stable aerosol properties and define the long-term influence of pyroCb activity on the stratospheric aerosol budget. Analysis of 13 years of airborne observations shows that pyroCb are responsible for 10 to 25% of the black carbon and organic aerosols in the "present-day" lower stratosphere, with similar impacts in both the North and South Hemispheres. These results suggest that, should pyroCb increase in frequency and/or magnitude in future climates, they could generate dominant trends in stratospheric aerosol.

3.
World J Urol ; 40(12): 3007-3013, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36289106

RESUMO

PURPOSE: To evaluate the impact of surgical caseload on safety, efficacy, and functional outcomes of laser enucleation of the prostate (LEP) applying a structured mentoring program. METHODS: Patient characteristics, perioperative data, and functional outcomes were analyzed descriptively. Linear and logistic regression models analyzed the effect of caseload on complications, functional outcomes and operative speed. Within the structured mentoring program a senior surgeon was present for the first 24 procedures completely, for partial steps in procedures 25-49, and as needed thereafter. RESULTS: A total of 677 patients from our prospective institutional database (2017-2022) were included for analysis. Of these, 84 (12%), 75 (11%), 82 (12%), 106 (16%), and 330 patients (49%) were operated by surgeons at (A) < 25, (B) 25-49, (C) 50-99, (D) 100-199, and (E) ≥ 200 procedures. Preoperative characteristics were balanced (all p > 0.05) except for prostate volume, which increased with caseload. There was no significant difference in change of IPSS, Quality of life, ICIQ, pad usage, peak urine flow, residual urine, and major complications (Group A: 8.3 to E: 7.6%, p = 0.2) depending on the caseload. Caseload was not associated (Odds ratio: 0.7-1.4, p > 0.2) with major complications in the multivariable logistic regression model. Only operating time was significantly shorter with increasing caseload in the multivariable analysis (111-55 min, beta 23.9-62.9, p < 0.001). CONCLUSION: With a structured mentoring program, the safety and efficacy of LEP can be ensured even during the learning curve with very good outcome quality. Only the operating time decreases significantly with increasing experience of the surgeon.


Assuntos
Terapia a Laser , Lasers de Estado Sólido , Hiperplasia Prostática , Cirurgiões , Ressecção Transuretral da Próstata , Masculino , Humanos , Curva de Aprendizado , Próstata/cirurgia , Qualidade de Vida , Estudos Prospectivos , Hiperplasia/complicações , Resultado do Tratamento , Hiperplasia Prostática/cirurgia , Hiperplasia Prostática/complicações , Terapia a Laser/métodos , Ressecção Transuretral da Próstata/métodos
5.
J Eur Acad Dermatol Venereol ; 36(8): 1157-1161, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35848143

RESUMO

Pustules are among the most common lesions produced in human skin. Infections by pathogens and drug-induced reactions are frequent causes of pustule formation. In recent years immune-mediated pustular diseases have drawn attention. It is proposed to classify pustular diseases according to the initiating events and sites: purely epidermal pustules, follicular pustules or pustules noted in autoinflammatory syndromes. The unifying pathology in all of the three categories is a microinvasion of activated neutrophils into epidermal or adnexal epithelia. Formation of pustules involves established IL-17 / IL-23, IL-36 / IL-36RN driven pathology, or IL-1 /caspase-activated autoinflammation. Pathophysiology demonstrates an intriguing synergy of keratinocytes with neutrophils. This is called keratinocyte-myeloid synergy (KMS). Non-infectious pustules are formed by IFNα controlling the production of chemoattractants (IL-8, LTB4) or induced by IL-1-regulated inflammasomes and caspase/ IFNß-induced chemotaxins. The presence of physical barriers, for example, cornified cell layers (str. corneum), is instrumental in establishing chemotactic gradients and blocking migrating neutrophils. In follicular KMS-driven pustular disorders, in contrast to epidermal pustules, neutrophil-mediated toxicity propagates lasting and expanding ulcerating diseases with increased levels of circulating immunoglobulin A (IgA). Complexed IgA is suggested to propagate ongoing pustular diseases. These are prerequisites essential for developing pustules in burdensome human skin diseases.


Assuntos
Exantema , Psoríase , Caspases , Humanos , Imunoglobulina A , Interleucina-1 , Queratinócitos/patologia , Neutrófilos/patologia , Psoríase/patologia
6.
J Dent Res ; 101(3): 323-330, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34528480

RESUMO

Nonsyndromic cleft lip with or without palate (nsCL/P) ranks among the most common human birth defects and has a multifactorial etiology. Human neural crest cells (hNCC) make a substantial contribution to the formation of facial bone and cartilage and are a key cell type in terms of nsCL/P etiology. Based on increasing evidence for the role of noncoding regulatory mechanisms in nsCL/P, we investigated the role of hNCC-expressed microRNAs (miRNA) in cleft development. First, we conducted a systematic analysis of miRNAs expressed in human-induced pluripotent stem cell-derived hNCC using Affymetrix microarrays on cell lines established from 4 unaffected donors. These analyses identified 152 candidate miRNAs. Based on the hypothesis that candidate miRNA loci harbor genetic variation associated with nsCL/P risk, the genomic locations of these candidates were cross-referenced with data from a previous genome-wide association study of nsCL/P. Associated variants were reanalyzed in independent nsCL/P study populations. Jointly, the results suggest that miR-149 is implicated in nsCL/P etiology. Second, functional follow-up included in vitro overexpression and inhibition of miR-149 in hNCC and subsequent analyses at the molecular and phenotypic level. Using 3'RNA-Seq, we identified 604 differentially expressed (DE) genes in hNCC overexpressing miR-149 compared with untreated cells. These included TLR4 and JUNB, which are established targets of miR-149, and NOG, BMP4, and PAX6, which are reported nsCL/P candidate genes. Pathway analyses revealed that DE genes were enriched in pathways including regulation of cartilage development and NCC differentiation. At the cellular level, distinct hNCC migration patterns were observed in response to miR-149 overexpression. Our data suggest that miR-149 is involved in the etiology of nsCL/P via its role in hNCC migration.


Assuntos
Fenda Labial , Fissura Palatina , MicroRNAs , Estudos de Casos e Controles , Fenda Labial/genética , Fissura Palatina/genética , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , MicroRNAs/genética , Crista Neural , Polimorfismo de Nucleotídeo Único
7.
Z Gerontol Geriatr ; 55(1): 27-31, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34170351

RESUMO

BACKGROUND: The dementia syndrome compromises effective communication and may thus lead to social isolation, psychological distress and decreased quality of life. It is therefore of importance to maintain communication capacity in dementia as long as possible. MATERIAL AND METHODS: A total of 24 professional caregivers from 8 nursing homes were assigned to train 254 of their respective colleagues using the train-the-trainer program MultiTANDEMplus. As in the 6 control nursing homes, severity of dementia, depressive symptoms and communication capacity were assessed in a total of 358 residents at baseline and 21 months later. Overall, 189 residents completed the study. RESULTS: Communication capacity declined in control home residents but remained stable in the intervention group although dementia severity increased in both groups. The intervention group exhibited significantly fewer depressive symptoms after the intervention than the control group. CONCLUSION: A standardized training of communication skills for professional caregivers can stabilize communication capacity and reduce depressive symptoms in nursing home residents. These effects are likely sustainable and could be demonstrated 21 months postintervention.


Assuntos
Demência , Qualidade de Vida , Comunicação , Humanos , Casas de Saúde , Estudos Prospectivos
9.
J Immigr Minor Health ; 23(6): 1187-1192, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33355905

RESUMO

Up until recently incidences of tuberculosis (TB) had been declining for many years in Germany. The rise in TB cases coincided with a large increase in the number of people applying for asylum. We combine data from various sources to estimate the at-entry prevalence of TB for asylum seekers from 18 countries of origin and rely on survey data to explain the varying risk of suffering from TB. Our results reveal that asylum seekers from Eastern Africa show a much higher risk of suffering from TB than asylum seekers from Afghanistan, Syria, or Iraq. The survey data suggests that asylum seekers from Africa were by far more underprivileged in their respective countries of origin and experienced a higher risk of contracting TB on their way to Germany. Information about the socio-economic situation and the circumstances of the journey to Germany may help to improve TB surveillance.


Assuntos
Refugiados , Tuberculose , Alemanha/epidemiologia , Humanos , Prevalência , Síria , Tuberculose/epidemiologia
10.
J Colloid Interface Sci ; 577: 319-328, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32497917

RESUMO

A fast, simple, instrument-free room temperature synthesis of stable electroactive surfactant-free colloidal Pt nanoparticles in alkaline methanol and methanol-water mixtures is presented. Pair distribution function (PDF) analysis suggests that methoxy substitution of chloride ligands from H2PtCl6 occurs in methanol. X-ray absorption spectroscopy (XAS) studies and UV-vis measurements show that solutions of H2PtCl6 in methanol age and are reduced to Pt(II) species over time. These species are ideal precursors to significantly reduce the induction period typically observed in colloidal Pt nanoparticle syntheses as well as the temperature needed to form nanoparticles. The room temperature synthesis presented here allows designing simple in situ studies of the nanoparticle formation. In situ infra-red spectroscopy gives insight into the formation and stabilization mechanism of surfactant-free nanoparticles by CO surface groups. Finally, the surfactant-free nanoparticles ca. 2-3 nm in diameter obtained are shown to be readily active electrocatalysts e.g. for methanol oxidation. The synthesis approach presented bears several advantages to design new studies and new syntheses of surfactant-free colloidal nanomaterials.

11.
Med Klin Intensivmed Notfmed ; 115(1): 43-51, 2020 Feb.
Artigo em Alemão | MEDLINE | ID: mdl-30397762

RESUMO

BACKGROUND: According to ILCOR (International Liaison Committee on Resuscitation) recommendations (released in 2003), use of therapeutic hypothermia is recommended for unconscious adult patients who have survived a cardiac arrest regardless of the initial monitored cardiac rhythm. Thereby, the treatment goal is to achieve and maintain a body temperature of 32-34 °C for a period of 12-24 h. According to the October 2015 recommendations of the European Resuscitation Council (ERC), targeted temperature management (TTM) remains part of treatment, but, as an option, it is advised that the targeted body temperature be 36 °C rather than 32-34 °C. PATIENT POPULATION AND METHODS: For a non-randomized retrospective observational study, a total of 149 patients were treated with cardiopulmonary resuscitation (CPR) between May 1999 and September 2009. For the first 4 days after CPR, data associated with demography, resuscitation, therapy (temperature course, neuron-specific enolase [NSE]) and clinical-neurological development (Glasgow Outcome Scale [GOS]) were collected. In the study, patients receiving mild hyperthermia were compared with those who did not receive hypothermia. RESULTS: Of the 149 patients included, 90 were treated with mild hypothermia (as decided by the attending physician), while 59 received no hypothermia therapy. Assessment reveals that mild hypothermia positively influences clinical-neurological progression, but not survival. On day three and four, patients with an unfavorable neurological progression exhibited significantly increased serum levels of NSE (day 4: 108.7 ± 137.3 ng/ml versus 25.5 ± 15.4 ng/ml). Patients receiving hypothermia showed lower average NSE levels compared with persons not receiving hypothermia. Furthermore, during the first 4 days, their NSE values tended to increase slower (NSE value at day 4: 55.9 ± 64.9 ng/ml versus 129.9 ± 174.9 ng/ml). The best cut-off-value for an unfavorable neurological result was 74.2 ng/ml at day four (specificity 100%, sensitivity 48.6%). For the group of patients who received hypothermia, the best cut-off-value was 74.2 ng/ml at day four (specificity 100%, sensitivity 40.9%), and, for the comparison group, best cut-off-value was 25.5 ng/ml at day three (specificity 100%, sensitivity 88.2%). CONCLUSION: After out-of-hospital resuscitation, there is a trend for improved clinical-neurological progression with mild hypothermia but it does not influence the prognostic significance of serum NSE. After assessment of available data, it is not possible to recommend uniform cut-off values for patients who received mild therapeutic hypothermia and for those who did not receive hypothermia treatment.


Assuntos
Reanimação Cardiopulmonar , Hipotermia Induzida , Parada Cardíaca Extra-Hospitalar , Fosfopiruvato Hidratase , Adulto , Humanos , Parada Cardíaca Extra-Hospitalar/diagnóstico , Parada Cardíaca Extra-Hospitalar/terapia , Fosfopiruvato Hidratase/análise , Prognóstico , Estudos Retrospectivos
12.
J Clin Invest ; 129(3): 1229-1239, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30620338

RESUMO

BACKGROUND: Sphingolipids are important components of cellular membranes and functionally associated with fundamental processes such as cell differentiation, neuronal signaling, and myelin sheath formation. Defects in the synthesis or degradation of sphingolipids leads to various neurological pathologies; however, the entire spectrum of sphingolipid metabolism disorders remains elusive. METHODS: A combined approach of genomics and lipidomics was applied to identify and characterize a human sphingolipid metabolism disorder. RESULTS: By whole-exome sequencing in a patient with a multisystem neurological disorder of both the central and peripheral nervous systems, we identified a homozygous p.Ala280Val variant in DEGS1, which catalyzes the last step in the ceramide synthesis pathway. The blood sphingolipid profile in the patient showed a significant increase in dihydro sphingolipid species that was further recapitulated in patient-derived fibroblasts, in CRISPR/Cas9-derived DEGS1-knockout cells, and by pharmacological inhibition of DEGS1. The enzymatic activity in patient fibroblasts was reduced by 80% compared with wild-type cells, which was in line with a reduced expression of mutant DEGS1 protein. Moreover, an atypical and potentially neurotoxic sphingosine isomer was identified in patient plasma and in cells expressing mutant DEGS1. CONCLUSION: We report DEGS1 dysfunction as the cause of a sphingolipid disorder with hypomyelination and degeneration of both the central and peripheral nervous systems. TRIAL REGISTRATION: Not applicable. FUNDING: Seventh Framework Program of the European Commission, Swiss National Foundation, Rare Disease Initiative Zurich.


Assuntos
Doenças do Sistema Nervoso Central , Ácidos Graxos Dessaturases , Erros Inatos do Metabolismo Lipídico , Mutação de Sentido Incorreto , Esfingosina , Substituição de Aminoácidos , Linhagem Celular , Doenças do Sistema Nervoso Central/enzimologia , Doenças do Sistema Nervoso Central/genética , Doenças do Sistema Nervoso Central/patologia , Ácidos Graxos Dessaturases/genética , Ácidos Graxos Dessaturases/metabolismo , Feminino , Humanos , Erros Inatos do Metabolismo Lipídico/enzimologia , Erros Inatos do Metabolismo Lipídico/genética , Erros Inatos do Metabolismo Lipídico/patologia , Masculino , Esfingosina/genética , Esfingosina/metabolismo , Sequenciamento do Exoma
13.
Geophys Res Lett ; 46(24): 14826-14835, 2019 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-33012881

RESUMO

During winter in the mid-latitudes, photochemical oxidation is significantly slower than in summer and the main radical oxidants driving formation of secondary pollutants, such as fine particulate matter and ozone, remain uncertain, owing to a lack of observations in this season. Using airborne observations, we quantify the contribution of various oxidants on a regional basis during winter, enabling improved chemical descriptions of wintertime air pollution transformations. We show that 25-60% of NOx is converted to N2O5 via multiphase reactions between gas-phase nitrogen oxide reservoirs and aerosol particles, with ~93% reacting in the marine boundary layer to form >2.5 ppbv ClNO2. This results in >70% of the oxidizing capacity of polluted air during winter being controlled, not by typical photochemical reactions, but from these multiphase reactions and emissions of volatile organic compounds, such as HCHO, highlighting the control local anthropogenic emissions have on the oxidizing capacity of the polluted wintertime atmosphere.

14.
Eur Spine J ; 28(2): 324-344, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30483961

RESUMO

INTRODUCTION AND PURPOSE: Little information exists on surgical characteristics, complications and outcomes with corrective surgery for rigid cervical kyphosis (CK). To collate the experience of international experts, the CSRS-Europe initiated an international multi-centre retrospective study. METHODS: Included were patients at all ages with rigid CK. Surgical and patient specific characteristics, complications and outcomes were studied. Radiographic assessment included global and regional sagittal parameters. Cervical sagittal balance was stratified according to the CSRS-Europe classification of sagittal cervical balance (types A-D). RESULTS: Eighty-eight patients with average age of 58 years were included. CK etiology was ankylosing spondlitis (n = 34), iatrogenic (n = 25), degenerative (n = 9), syndromatic (n = 6), neuromuscular (n = 4), traumatic (n = 5), and RA (n = 5). Blood loss averaged 957 ml and the osteotomy grade 4.CK-correction and blood loss increased with osteotomy grade (r = 0.4/0.6, p < .01). Patients with different preop sagittal balance types had different approaches, preop deformity parameters and postop alignment changes (e.g. C7-slope, C2-7 SVA, translation). Correction of the regional kyphosis angle (RKA) was average 34° (p < .01). CK-correction was increased in patients with osteoporosis and osteoporotic vertebrae (POV, p = .006). 22% of patients experienced a major long-term complication and 14% needed revision surgery. Patients with complications had larger preop RKA (p = .01), RKA-change (p = .005), and postop increase in distal junctional kyphosis angle (p = .02). The POV-Group more often experienced postop complications (p < .0001) and revision surgery (p = .02). Patients with revision surgery had a larger RKA-change (p = .003) and postop translation (p = .04). 21% of patients had a postop segmental motor deficit and the risk was elevated in the POV-Group (p = .001). CONCLUSIONS: Preop patient specific, radiographic and surgical variables had a significant bearing on alignment changes, outcomes and complication occurrence in the treatment of rigid CK.


Assuntos
Vértebras Cervicais , Cifose , Vértebras Cervicais/patologia , Vértebras Cervicais/fisiopatologia , Vértebras Cervicais/cirurgia , Europa (Continente) , Humanos , Cifose/patologia , Cifose/fisiopatologia , Cifose/cirurgia , Pessoa de Meia-Idade , Procedimentos Ortopédicos , Estudos Retrospectivos , Resultado do Tratamento
15.
Oper Orthop Traumatol ; 30(6): 419-434, 2018 Dec.
Artigo em Alemão | MEDLINE | ID: mdl-30443745

RESUMO

OBJECTIVE: Minimally invasive endoscopic reconstruction of avulsion injuries of the proximal hamstring insertion to prevent persistent weakness and pain. INDICATIONS: Fresh retracted 2­ and 3­tendon avulsion injuries of the proximal hamstring insertion. Unsuccessful conservative therapy of less retracted injuries. Painful chronic partial lesions of the proximal hamstring insertion. CONTRAINDICATIONS: Major comorbidities with an increased surgical risk, older patients with low functional demands. Chronic injuries without functional deficits. SURGICAL TECHNIQUE: Endoscopic refixation using suture anchors after freshening the footprint on the tuber ischiadicum. Visualization of the sciatic nerve to ensure its protection. POSTOPERATIVE MANAGEMENT: Partial loading with a knee brace for strict prevention of combined knee extension and hip flexion for 4-6 weeks. Start of active exercise and stretching 8 weeks postoperatively. RESULTS: From 2014-2016, 12 patients were treated with an endoscopic reconstruction of the proximal hamstring insertion. After a mean follow-up of 25 months (range 16-34 months), an average visual analog scale (VAS) of 0 (range 0-2) and an average subjective assessment of function (Subjective Hip Value) of 94% (range 80-100%) were found. No neurovascular complications were seen in our collective, in particular no evidence of hypesthesia in the area of the posterior femoral cutaneous nerve. All patients were able to return to their original level of activity (Tegner Activity Scale 5.2 preoperatively vs. 5.2 postoperatively), while the average time until return to sport was 6.5 months (range 3-12 months). All patients were able to return to their original occupation.


Assuntos
Lesões do Quadril/cirurgia , Procedimentos Cirúrgicos Minimamente Invasivos , Traumatismos dos Tendões , Humanos , Amplitude de Movimento Articular , Âncoras de Sutura , Traumatismos dos Tendões/cirurgia , Coxa da Perna , Resultado do Tratamento
16.
Nutr Metab Cardiovasc Dis ; 28(11): 1100-1105, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30143407

RESUMO

BACKGROUND AND AIMS: Chronic inflammatory diseases (CID) are associated with a profound increase in cardiovascular (CV) risk resulting in reduced life expectancy. However, LDL-cholesterol is reported to be low in CID patients which is referred to as the "LDL paradoxon". The aim of the present study was to investigate whether LDL-particles in CID exhibit an increased content of the highly atherogenic small-dense LDL subfraction (sdLDL). METHODS AND RESULTS: In this prospective, single center, observational study we enrolled 141 patients with CID (RA n = 59, inflammatory bowel disease (IBD) n = 35, ankylosing spondylitis (SpA) n = 25, Psoriasis n = 22) in 2011 through 2013 to evaluate sdLDL levels before as well as 6 and 26 weeks after initiation of different anti-cytokine therapies (anti-TNFα, anti-IL-6R antibodies). sdLDL levels were compared to 141 healthy individuals in a case control design. Compared to healthy controls, all CID patients displayed a significantly higher sdLDL content within the LDL cholesterol fraction: RA 35.0 ± 9.2% (p < 0.001), SpA 42.5 ± 10.5% (p < 0.001), IBD 37.5 ± 7.1% (p < 0.001), Psoriasis 33.6 ± 4.6% (p < 0.01). Furthermore, the sdLDL/LDL ratio was significantly higher in male compared to female RA subjects (p < 0.05). Neither anti-TNFα nor anti-IL6R medication altered sdLDL levels despite a significant improvement of disease activity. CONCLUSION: In several different chronic inflammatory disease entities, LDL-cholesterol is shifted toward a pro-atherogenic phenotype due to an increased sdLDL content which might in part explain the LDL paradoxon. Since premature CV disease is a major burden of affected patients, specifically targeting lipid metabolism should be considered routinely in clinical patient care. CLINICAL TRIALS: Registration at German Clinical Trial Register (DRKS): DRKS00005285.


Assuntos
Aterosclerose/sangue , LDL-Colesterol/sangue , Doenças Inflamatórias Intestinais/sangue , Psoríase/sangue , Espondilite Anquilosante/sangue , Adulto , Idoso , Anti-Inflamatórios/uso terapêutico , Aterosclerose/diagnóstico , Aterosclerose/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Doença Crônica , Feminino , Alemanha , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/imunologia , Masculino , Pessoa de Meia-Idade , Tamanho da Partícula , Fenótipo , Estudos Prospectivos , Psoríase/diagnóstico , Psoríase/tratamento farmacológico , Psoríase/imunologia , Receptores de Interleucina-6/antagonistas & inibidores , Receptores de Interleucina-6/imunologia , Fatores de Risco , Espondilite Anquilosante/diagnóstico , Espondilite Anquilosante/tratamento farmacológico , Espondilite Anquilosante/imunologia , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Fator de Necrose Tumoral alfa/imunologia
17.
Clin Genet ; 94(5): 467-472, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30028002

RESUMO

Biallelic SBF2 mutations cause Charcot-Marie-Tooth disease type 4B2 (CMT4B2), a sensorimotor neuropathy with autosomal recessive inheritance and association with glaucoma. Since the discovery of the gene mutation, only few additional patients have been reported. We identified seven CMT4B2 families with nine different SBF2 mutations. Revisiting genetic and clinical data from our cohort and the literature, SBF2 variants were private mutations, including exon-deletion and de novo variants. The neuropathy typically started in the first decade after normal early motor development, was predominantly motor and had a rather moderate course. Electrophysiology and nerve biopsies indicated demyelination and excess myelin outfoldings constituted a characteristic feature. While neuropathy was >90% penetrant at age 10 years, glaucoma was absent in ~40% of cases but sometimes developed with age. Consequently, SBF2 mutation analysis should not be restricted to individuals with coincident neuropathy and glaucoma, and CMT4B2 patients without glaucoma should be followed for increased intraocular pressure. The presence of exon-deletion and de novo mutations demands comprehensive mutation scanning and family studies to ensure appropriate diagnostic approaches and genetic counseling.


Assuntos
Doença de Charcot-Marie-Tooth/diagnóstico , Doença de Charcot-Marie-Tooth/genética , Estudos de Associação Genética , Predisposição Genética para Doença , Mutação , Fenótipo , Proteínas Tirosina Fosfatases não Receptoras/genética , Adolescente , Adulto , Biópsia , Criança , Feminino , Estudos de Associação Genética/métodos , Humanos , Masculino , Adulto Jovem
18.
J Nutr Health Aging ; 22(4): 555-561, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29582897

RESUMO

Ageing is associated with redistribution of fat around the body and saturation of visceral adipose depots. Likewise, the presence of excess fat in obesity or during ageing places extra stress on visceral depots, resulting in chronic inflammation and increased senescence. This process can contribute to the establishment of the metabolic syndrome and accelerated ageing. Dietary restriction (DR) is known to alleviate physiological signs of inflammation, ageing and senescence in various tissues including adipose tissue. OBJECTIVES: Our pilot study aimed to analyse senescence and inflammation parameters in mouse visceral fat tissue during ageing and by short term, late-onset dietary restriction as a nutritional intervention. Design, measurements: In this study we used visceral adipose tissue from mice between 5 and 30 months of age and analysed markers of senescence (adipocyte size, γH2A.X, p16, p21) and inflammation (e.g. IL-6, TNFα, IL-1ß, macrophage infiltration) using immuno-staining, as well as qPCR for gene expression analysis. Fat tissues from 3 mice per group were analysed. RESULTS: We found that the amount of γH2A.X foci as well as the expression of senescence and inflammation markers increased during ageing but decreased with short term DR. In contrast, the increase in amounts of single or aggregated macrophages in fat depots occurred only at higher ages. Surprisingly, we also found that adipocyte size as well as some senescence parameters decreased at very high age (30 months). CONCLUSIONS: Our results demonstrate increased senescence and inflammation during ageing in mouse visceral fat while DR was able to ameliorate several of these parameters as well as increased adipocyte size at 17.5 months of age. This highlights the health benefits of a decreased nutritional intake over a relatively short period of time at middle age.


Assuntos
Adiposidade/fisiologia , Envelhecimento/fisiologia , Dano ao DNA/genética , Privação de Alimentos/fisiologia , Inflamação/fisiopatologia , Gordura Intra-Abdominal/fisiopatologia , Fatores Etários , Animais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Projetos Piloto
19.
J Surg Case Rep ; 2018(2): rjy016, 2018 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29492249

RESUMO

Use of ventricular assist devices (VADs) is increasingly common, as is the need for surgeons to be familiar with the management of common complications in this population. Nonetheless, repair of diaphragmatic hernias which commonly develop following VAD implantation remains technically challenging due to intra-abdominal adhesions and the proximity of vital structures. Despite the potential benefits of improved dexterity and visualization, robotic approaches have thus far not been used to address this. We present the first two described cases of robot-assisted repair of diaphragmatic hernias in the setting of prior or current VAD placement.

20.
Orthopade ; 47(3): 238-245, 2018 Mar.
Artigo em Alemão | MEDLINE | ID: mdl-29327070

RESUMO

BACKGROUND: Operative refixation is a new therapeutic option in cases of failed conservative treatment for trochanteric pain syndrome (TPS) and lesions of the hip abductors in magnetic resonance imaging (MRI). OBJECTIVE: Evaluation of the clinical and radiological results after open gluteus medius and minimus tendon reconstruction with a double-row technique was carried out. MATERIAL AND METHODS: Patients with failed conservative treatment for TPS and confirmed lesions of the hip abductors in MRI were treated by open hip abductor tendon reconstruction with a double-row technique. The patients were evaluated preoperatively and postoperatively (minimum follow-up 12 months) using the modified Harris hip score (mHHS) and a subjective score (subjective hip value, SHV). Preoperative and postoperative MRI evaluation included measurement of hip abductor muscle diameter and cross-sectional area as well as fatty degeneration. RESULTS: In this study 12 consecutive cases of open reconstruction of the hip abductor tendons were included. There was a significant improvement in the mHHS. In one case the patient showed an atraumatic rupture in the proximal anchor row. The MRI showed a significant improvement in muscle diameter and cross-sectional area for the gluteus medius muscle of the affected and the contralateral side, while the degree of fatty degeneration did not improve. The fatty degeneration showed a significant correlation with the postoperative results in the mHHS and the SHV. CONCLUSION: Operative reconstruction of lesions in the hip abductor tendons is a therapy option with significant improvement of patient satisfaction and functional scores as well as muscle diameter and cross-sectional area for the gluteus medius. The degree of fatty degeneration and possible differential diagnoses need to be taken into consideration.


Assuntos
Nádegas/lesões , Músculo Esquelético/lesões , Complicações Pós-Operatórias/diagnóstico por imagem , Traumatismos dos Tendões/cirurgia , Adulto , Idoso , Nádegas/diagnóstico por imagem , Nádegas/cirurgia , Seguimentos , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/diagnóstico por imagem , Músculo Esquelético/cirurgia , Estudos Retrospectivos , Traumatismos dos Tendões/diagnóstico por imagem
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