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2.
J Dtsch Dermatol Ges ; 22(2): 236-264, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38229208

RESUMO

Changes in the microcirculation of the skin are a frequently observed accompanying phenomenon of many diseases, far beyond the spectrum of dermatological diseases. Not all of these changes are pathological, many are transient and have no serious consequences. This is true for many inflammatory diseases such as psoriasis vulgaris or atopic eczema. However, there are also diseases in which functionally and morphologically recognizable microangiopathies lead to severe disease consequences. One of the most important diseases in this context is systemic sclerosis, an autoimmune systemic disease with multiple organ manifestations. Investigations of the cutaneous microcirculation are of great importance for the initial diagnosis as well as for prognosis and assessment of disease progression. In peripheral hemodynamic disorders such as peripheral arterial disease (PAD) and chronic venous insufficiency (CVI), understanding microcirculatory disturbances also plays an important role in therapy and in monitoring the success of therapeutic interventions.


Assuntos
Dermatite Atópica , Psoríase , Insuficiência Venosa , Humanos , Microcirculação , Pele/patologia , Insuficiência Venosa/terapia , Psoríase/complicações , Dermatite Atópica/diagnóstico , Dermatite Atópica/complicações
3.
Clin Pract ; 14(1): 132-147, 2024 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-38248435

RESUMO

BACKGROUND: Cardiovascular diseases and arrhythmias are medical conditions that increase with age and are associated with significant morbidities and mortality. The aim of the present study was to investigate the prevalence of arrhythmias and clinical associations in the collective of older adults receiving comprehensive geriatric care (CGC). METHODS: Holter ECG monitoring (HECG) of older patients hospitalized for CGC was analyzed. The prevalence of arrhythmias and the associations between the presence of arrhythmias, patients' characteristics and the functional status regarding basic activities of daily living (assessed by the Barthel index (BI)), walking ability (assessed by the timed up and go test (TUG)), and balance and gait (assessed by the Tinetti balance and gait test (TBGT)) were examined. RESULTS: In the presented study, 626 patients were included (mean age: 83.9 ± 6.6 years, 67.7% were female). The most common arrhythmias detected in HECG were premature ventricular contractions (87.2%), premature atrial contractions (71.7%), and atrial fibrillation (22.7%). Atrial flutter was found in 1.0%, paroxysmal supraventricular tachycardia in 5.8%, non-sustained ventricular tachycardia in 12.5%, first-degree AV block in 0.8%, second-degree AV block type Mobitz I in 0.8%, second-degree AV block type Mobitz II in 0.3%, pause > 2.5 s any cause in 3.5%, and pause > 3 s any cause in 1.6% of the cases. Premature atrial contractions were associated with the female sex (74.8% vs. 65.3%, p = 0.018), whereas in male patients, the following arrhythmias were more common: premature ventricular contractions (91.6% vs. 85.1%, p = 0.029), ventricular bigeminus (8.4% vs. 3.8%, p = 0.021), and non-sustained ventricular tachycardia (17.3% vs. 10.1%, p = 0.014). Atrial fibrillation detected in HECG was more frequent in patients at high risk of falls, indicated by their TBGT score ≤ 18 (24.7% vs. 12.0%, p = 0.006), and premature ventricular contractions were more common in patients unable to walk (TUG score 5) compared to those with largely independent mobility (TUG score 1 or 2) (88.0% vs. 75.0%, p = 0.023). In a logistic regression analysis, atrial fibrillation detected in HECG was identified as a risk factor for a high risk of falls (odds ratio (OR): 2.35, 95% confidence interval (CI): 1.23-4.46). CONCLUSION: In our study, investigation of HECG of older adults hospitalized for CGC revealed that premature atrial contractions, premature ventricular contractions, and atrial fibrillation were the most common arrhythmias. Premature atrial contractions were found to be more frequent in female patients, while male patients were more prone to premature ventricular contractions. In the investigated population, atrial fibrillation emerged as a risk factor associated with a high risk of falls.

4.
Cancers (Basel) ; 16(2)2024 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-38275911

RESUMO

Cutaneous squamous cell carcinomas (SCCs) are a major complication of some subtypes of epidermolysis bullosa (EB), with high morbidity and mortality rates and unmet therapeutic needs. The high rate of endogenous mutations and the fibrotic stroma are considered to contribute to the pathogenesis. Patients with dystrophic EB (DEB) and Kindler EB (KEB) have the highest propensity for developing SCCs. Another patient group that develops high-risk SCCs is immunosuppressed (IS) patients, especially after organ transplantation. Herein, we interrogate whether immune checkpoint proteins and immunosuppressive enzymes are dysregulated in EB-associated SCCs as an immune resistance mechanism and compare the expression patterns with those in SCCs from IS patients, who frequently develop high-risk tumors and sporadic SCCs, and immunocompetent (IC) individuals. The expression of indoleamine 2,3-dioxygenase (IDO), programmed cell death protein-1 (PD-1), programmed cell death ligand-1 (PD-L1), T cell immunoglobulin and mucin-domain-containing protein-3 (TIM-3), lymphocyte activation gene-3 (LAG-3), and inflammatory infiltrates (CD4, CD8, and CD68) was assessed via immunohistochemistry and semi-quantitative analysis in 30 DEB-SCCs, 22 KEB-SCCs, 106 IS-SCCs, and 100 sporadic IC-SCCs. DEB-SCCs expressed significantly higher levels of IDO and PD-L1 in tumor cells and PD-1 in the tumor microenvironment (TME) compared with SCCs from IC and IS individuals. The number of CD4-positive T cells per mm2 was significantly lower in DEB-SCCs compared with IC-SCCs. KEB-SCCs showed the lowest expression of the exhaustion markers TIM-3 and LAG-3 compared with all other groups. These findings identify IDO, PD-1, and PD-L1 to be increased in EB-SCCs and candidate targets for combinatory treatments, especially in DEB-SCCs.

5.
Sleep Breath ; 2023 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-37889457

RESUMO

PURPOSE: To analyze sleep characteristics as measured with polysomnography (PSG) in adults from the general population with and without physician-diagnosed atopic dermatitis (AD). METHODS: We analyzed data from participants from the German population-based Study of Health in Pomerania (SHIP) TREND-0. AD was diagnosed in a standardized skin examination. The following polysomnographic parameters were measured: total sleep duration (min), sleep latency (min), wake after sleep onset (WASO; min), rapid eye movement (REM) latency (min), sleep efficiency (%), total number of wakefulness and movement episodes, stages of sleep (%), and apnea-hypopnea index (AHI). Additionally, the subjective sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI). We compared sleep characteristics of participants with and without AD. RESULTS: Among 1187 participants, 47 (4.0%) had AD. We found no differences between participants with and without AD in any of the analyzed PSG parameters except for the total number of wakefulness and movement episodes and the percentage of REM sleep. Participants with AD had a higher number of wakefulness and movement episodes, and a lower proportion of REM sleep compared to those without AD. Regarding subjective sleep parameters, no significant differences were found between participants with and without AD. CONCLUSION: Our data do not provide evidence for poor sleep quality in individuals with AD. Major limitations of the study include the unavailability of data on AD severity and the small number of participants with AD. Larger-scaled longitudinal studies considering disease severity and specific AD symptoms with an effect on sleep are required.

6.
Cureus ; 15(5): e38929, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-37309341

RESUMO

INTRODUCTION: The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in patients with Mycosis Fungoides (MF), as well as with Graft-versus-Host Disease (GvHD). METHODS: LQ was monitored retrospectively by using the dermatology life quality index (DLQI) and Skindex-29 test before ECP onset and after the last ECP. Disease parameters were assessed by objective criteria i.e. number of associated medical drugs taken, intervals between therapeutic cycles, gradual change of the disease, and eventual side-effects and complications of ECP therapy. RESULTS: Fifty-one patients were treated with ECP during 2008-19; 19 out of 51 died, and follow-up was not completed in 13 patients. Finally, treatment protocols of 671 ECP procedures were evaluated in 19 patients (10 MF; 9 GvHD). MF and GvHD subpopulations did not differ in the individual scores of LQ questions, either before the outset or after the last ECP. DLQI and Skindex-29 scores were ameliorated by the ECP therapy (p= 0.001 and p< 0.001, respectively) due to improvement of individual scores of feelings, daily/social activities (p< 0.05), and functionality (p≤ 0.05). The median interval between ECP cycles was extended from two to eight weeks (p= 0.001). Needs of GvHD patients for drugs being received for the underlying disease were reduced (p= 0.035). Two of the 10 MF patients worsened from stage IIA to IIIA. Severe or minor side effects leading to a therapy interruption were not recorded. CONCLUSION: Patients with GvHD experienced a notable decrease in the administration of drugs for their underlying condition, and there were no instances of severe side effects that resulted in the discontinuation of treatment. ECP is safe and effective for the treatment of MF and GvHD.

7.
Med Sci (Basel) ; 11(2)2023 05 29.
Artigo em Inglês | MEDLINE | ID: mdl-37367739

RESUMO

BACKGROUND/OBJECTIVES: Comprehensive Geriatric Care (CGC) is a specific multimodal treatment for older patients. In the current study, we aimed to investigate walking performance after CGC in medically ill patients versus those with fractures. METHODS: The timed up and go test (TuG), a 5-grade scale assessment (1 = no walking impairment to 5 = no walking ability at all) for evaluating individual walking ability was performed in all patients who underwent CGC prior to and after treatment. Factors associated with improvement in walking ability were analyzed in the subgroup of patients with fractures. RESULTS: Out of 1263 hospitalized patients, 1099 underwent CGC (median age: 83.1 years (IQR 79.0-87.8 years); 64.1% were female). Patients with fractures (n = 300) were older than those without (n = 799), (median 85.6 versus 82.4 years, p = 0.001). Improvement in TuG after CGC was found in 54.2% of the fracture patients compared to just 45.9% of those without fractures. In fracture group patients, TuG improved from median 5 on admission to median 3 on discharge (p = 0.001). In fracture patients, improvement in walking ability was associated with higher Barthel index values on admission (median 45 (IQR: 35-55) versus 35 (IQR: 20-50): p = 0.001) and Tinetti assessment scores (median 9 (IQR: 4-14.25) versus 5 (IQR: 0-13); p = 0.001) and was negatively associated with the diagnosis of dementia (21.4% versus 31.5%; p = 0.058). CONCLUSION: CGC improved walking ability in more than half of all patients examined. Older patients in particular might benefit from undergoing the procedure after an acute fracture. A better initial functional status favors a positive result following the treatment.


Assuntos
Fraturas do Quadril , Humanos , Feminino , Idoso , Idoso de 80 Anos ou mais , Masculino , Equilíbrio Postural , Estudos de Tempo e Movimento , Atividades Cotidianas , Assistência Integral à Saúde
8.
Geriatrics (Basel) ; 8(2)2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36960987

RESUMO

BACKGROUND: Comprehensive geriatric care (CGC) is a multiprofessional treatment for older people which considers medical conditions and functional status. The aim of the presented study is to investigate the impact of hypertensive blood pressure (BP) on functional outcomes among older adults receiving CGC. METHODS: Functional status was documented by the Barthel index (BI), Tinetti test (TBGT), and timed up and go test (TUG) prior to and after CGC. The results were analyzed in relation to hypertensive BP, indicated by mean BP ≥ 130/80 mmHg determined by 24 h blood pressure monitoring (BPM) while hospitalized. RESULTS: In the presented monocentric, retrospective, observational study, 490 patients were included (mean age (SD): 83.86 ± 6.17 years, 72.2% females). Hypertension in BPM was found in 302 (61.6%) individuals. Hypertensive BP was associated with the female sex (p < 0.001) and current fracture (p = 0.001), and inversely associated with heart failure (p < 0.001), coronary heart disease (p < 0.001), atrial fibrillation (p < 0.001), urinary tract infection (p = 0.022), and hypocalcemia (p = 0.014). After CGC, improvements in BI (p < 0.001), TBGT (p < 0.001), and TUG (p < 0.001) were observed in patients with both normotensive and hypertensive BP profiles. The proportion of patients with outcome improvements did not differ between the two groups (BI: 84.4% vs. 88.3%, p = 0.285; TBGT: 81.1% vs. 77.7%, p = 0.357; TUG: 50.3% vs. 48.4%, p = 0.711). CONCLUSION: Patients both with and without hypertensive BP profiles benefited from comprehensive geriatric care with comparable outcome improvements. Particularly, normotensive BP was associated with chronic cardiovascular comorbidities, indicating increased awareness of the importance of BP management in patients diagnosed with cardiac diseases.

9.
Geriatrics (Basel) ; 8(2)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36960992

RESUMO

BACKGROUND/OBJECTIVES: Depressive symptoms (DS) may interfere with comprehensive geriatric care (CGC), the specific multimodal treatment for older patients. In view of this, the aim of the current study was to investigate the extent to which DS occur in older hospitalized patients scheduled for CGC and to analyze the associated factors. Furthermore, we aimed to investigate whether DS are relevant with respect to outcomes after CGC. METHODS: For this retrospective study, all patients fulfilling the inclusion criteria were selected by reviewing case files. The main inclusion criterion was the completion of CGC within the defined period (May 2018 and May 2019) in the geriatrics department of the Diakonie Hospital Jung-Stilling Siegen (Germany). The Geriatric Depression Scale was used to asses DS in older adults scheduled for CGC (0-5, no evidence of DS; 6-15 points, DS). Scores for functional assessments (Timed Up and Go test (TuG), Barthel Index, and Tinetti Gait and Balance test) were compared prior to versus after CGC. Factors associated with the presence of DS were studied. RESULTS: Out of the 1263 patients available for inclusion in this study, 1092 were selected for the analysis (median age: 83.1 years (IQR 79.1-87.7 years); 64.1% were female). DS (GDS > 5) were found in 302 patients (27.7%). The proportion of female patients was higher in the subgroup of patients with DS (85.5% versus 76.3%, p = 0.024). Lower rates of patients diagnosed with chronic pulmonary obstructive disease were detected in the subgroup of patients without DS (8.0% versus 14.9%, p = 0.001). Higher rates of dizziness were observed in patients with DS than in those without (9.9% versus 6.2%, p = 0.037). After CGC, TuG scores improved from a median of 4 to 3 (p < 0.001) and Barthel Index scores improved from a median of 45 to 55 (p < 0.001) after CGC in both patients with and without DS. In patients with DS, the Tinetti score improved from a median of 10 (IQR: 4.75-14.25) prior to CGC to 14 (IQR 8-19) after CGC (p < 0.001). In patients without DS, the Tinetti score improved from a median of 12 (IQR: 6-7) prior to CGC to 15 (IQR 2-20) after CGC (p < 0.001). CONCLUSIONS: DS were detected in 27.7% of the patients selected for CGC. Although patients with DS had a poorer baseline status, we detected no difference in the degree of improvement in both groups, indicating that the performance of CGC is unaffected by the presence of DS prior to the procedure.

10.
Nat Commun ; 14(1): 813, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36781877

RESUMO

Terpene cyclases catalyze one of the most powerful transformations with respect to efficiency and selectivity in natural product (bio)synthesis. In such polyene cyclizations, structurally highly complex carbon scaffolds are built by the controlled ring closure of linear polyenes. Thereby, multiple C,C bonds and stereocenters are simultaneously created with high precision. Structural pre-organization of the substrate carbon chain inside the active center of the enzyme is responsible for the product- and stereoselectivity of this cyclization. Here, we show that in-situ formed fluorinated-alcohol-amine supramolecular clusters serve as artificial cyclases by triggering enzyme-like reactivity and selectivity by controlling substrate conformation in solution. Because of the dynamic nature of these supramolecular assemblies, a broad range of terpenes can be produced diastereoselectively. Mechanistic studies reveal a finely balanced interplay of fluorinated solvent, catalyst, and substrate as key to establishing nature's concept of a shape-selective polyene cyclization in organic synthesis.

11.
Hear Res ; 429: 108700, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36680872

RESUMO

BACKGROUND AND AIMS: Conserved specimens do not decay and therefore permit long-term experiments thereby overcoming limited access to fresh (frozen) temporal bones for studies on middle ear mechanics. We used a Thiel conservation method which is mainly based on a watery solution of salts. In contrast to pure Formalin, Thiel conservation aims to preserve the mechanical proprieties of human tissue. The aim of this study is to examine the effect of Thiel conservation on bone conduction in the same specimen before and after conservation. METHODS: Nine ears of five defrosted whole heads were stimulated with a direct, electrically driven, bone anchored hearing system (Baha, Baha SuperPower). The motion produced by bone conduction stimulation was measured with a single point laser Doppler vibrometer (LDV) at the promontory, the ossicular chain, and the round window through a posterior tympanotomy. After the initial experiments, the entire whole heads were placed in Thiel solution. In order to enable direct comparison between fresh frozen and Thiel specimens, our Thiel conservation did not include intravascular and intrathecal perfusion. The measurements were repeated 3 and 12 months later. To determine the effect of freezing, defrosting, and embalming on the whole heads, CT scans were performed at different stages of the experimental procedure. Additionally, three extracted temporal bones were stimulated a Baha, motion of the promontory measured by LDV and embalmed in Thiel solution to investigate the direct impact of Thiel solution on the bone. RESULTS: The averaged magnitude of motion on the promontory increased in whole head specimens by a mean of 10.3 dB after 3 months of Thiel embalming and stayed stable after 12 months. A similar effect was observed for motion at the tympanic membrane (+7.2 dB), the stapes (+9.5 dB), and the round window (+4.0 dB). In contrast to the whole head specimens, the motion of the extracted temporal bones did not change after 3 months of Thiel embalming (-0.04 dB in average). CT scans of the whole heads after conservation showed a notable brain volume loss mostly >50% as well as a remarkable change in the consistency and structure of the brain. Partial changes could already be observed before the Thiel embalming but after 1-2 days of defrosting. In an additional experiment, a substitution of brain mass and weight by Thiel fluid did not lead to new deterioration in sound transmission. In contrast, a frozen (non-defrosted) whole head showed a distinctively reduced magnitude of promontory motion before defrosting. DISCUSSION: For our setup, the vibration of the ear due to bone conduction in the same whole head specimens significantly increased after Thiel conservation. Such an increase was not observed in extracted temporal bone specimens. Due to brain changes in the CT scans, we investigated the consequences of the brain volume changes and structure loss on the frozen brain before defrosting. The loss of brain volume alone could not explain the increase of ear vibrations, as we did not observe a difference when the volume was replaced with Thiel fluid. However, freezing and defrosting of the entire brain seems to have a major influence. Beside the destructive effect of freezing on the brain, the modified conservation method without perfusion changed the brain structure. In conclusion, bone conduction in whole heads depends on the physical condition of the brain, rather than on the conservation.


Assuntos
Condução Óssea , Embalsamamento , Humanos , Condução Óssea/fisiologia , Congelamento , Cadáver , Orelha Média/fisiologia , Vibração
12.
Int J Audiol ; 62(2): 192-198, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-35174741

RESUMO

OBJECTIVE: The Vibrant Soundbridge (VSB) is one of the most widely used implantable hearing devices. It consists of a vibrating floating mass transducer (FMT) that is connected to a middle ear structure. The standard coupling devices for sensorineural hearing loss are short process (SP) or long process (LP) couplers. DESIGN AND STUDY SAMPLE: This study directly compared the electro-mechanical performance of the SP- and LP-coupled FMT of the VSB in the same temporal bone specimen (n = 10). We measured velocity magnitudes and total harmonic distortions (THD) of the stapes (ST) and the round window (RW) using laser Doppler Vibrometry (LDV). RESULTS: Comparison shows a maximally 10 dB higher magnitude for the LP coupler at ST and RW for frequencies below 600 Hz, whereas the SP coupler shows a maximally 20 dB higher magnitude at the ST and RW for frequencies above 600 Hz. THD show similar behaviour with less distortion at 500 Hz for the LP coupler and less distortions for the SP coupler in higher frequencies. CONCLUSIONS: Our experiments showed that the SP coupling may be mechanically favourable, in terms of magnitude and distortion, for the transmission of FMT vibrations at higher frequencies.


Assuntos
Perda Auditiva Condutiva-Neurossensorial Mista , Prótese Ossicular , Humanos , Bigorna , Orelha Média , Estribo , Osso Temporal
13.
Mol Neurobiol ; 60(2): 820-835, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36378468

RESUMO

Musashi RNA-binding proteins (MSIs) retain a pivotal role in stem cell maintenance, tumorigenesis, and nervous system development. Recently, we showed in C. elegans that Musashi (MSI-1) actively promotes forgetting upon associative learning via a 3'UTR-dependent translational expression of the Arp2/3 actin branching complex. Here, we investigated the evolutionary conserved role of MSI proteins and the effect of their pharmacological inhibition on memory. Expression of human Musashi 1 (MSI1) and Musashi 2 (MSI2) under the endogenous Musashi promoter fully rescued the phenotype of msi-1(lf) worms. Furthermore, pharmacological inhibition of human MSI1 and MSI2 activity using (-)- gossypol resulted in improved memory retention, without causing locomotor, chemotactic, or learning deficits. No drug effect was observed in msi-1(lf) treated worms. Using Western blotting and confocal microscopy, we found no changes in MSI-1 protein abundance following (-)- gossypol treatment, suggesting that Musashi gene expression remains unaltered and that the compound exerts its inhibitory effect post-translationally. Additionally, (-)- gossypol suppressed the previously seen rescue of the msi-1(lf) phenotype in worms expressing human MSI1 specifically in the AVA neuron, indicating that (-)- gossypol can regulate the Musashi pathway in a memory-related neuronal circuit in worms. Finally, treating aged worms with (-)- gossypol reversed physiological age-dependent memory decline. Taken together, our findings indicate that pharmacological inhibition of Musashi might represent a promising approach for memory modulation.


Assuntos
Caenorhabditis elegans , Gossipol , Idoso , Animais , Humanos , Caenorhabditis elegans/metabolismo , Gossipol/farmacologia , Gossipol/metabolismo , Transtornos da Memória/tratamento farmacológico , Proteínas do Tecido Nervoso/metabolismo , Neurônios/metabolismo , Proteínas de Ligação a RNA/metabolismo , Células-Tronco/metabolismo
14.
Medicine (Baltimore) ; 101(42): e31092, 2022 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-36281128

RESUMO

OBJECTIVE: To evaluate the sensitivity and specificity of 2-18fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) and ultrasound (US) for staging patients with malignant melanoma. METHODS: In total, 258 patients (112 men and 146 women; mean age, 61 ± 16years) met the primary inclusion criteria for malignant melanoma without further malignancy proven by histopathology. This was a retrospective study of the diagnostic accuracy. All data were obtained from the hospital's patient and radiology information system. Patients formed a consecutive series and were examined by 18F-FDG PET/CT and 176 additionally by US (US as a whole [wUS], peripheral lymph nodes [pUS], abdomen [aUS]), with a total of 584 18F-FDG PET/CT and 697 US. 18F-FDG PET/CT and US revealed 824 and 726 lesions, respectively. Per-patient, per-examination, and per-lesion analyses were also performed. The reference standards used were histopathology or resection of lesions, and follow-up controls using other imaging methods. RESULTS: Significant differences (P < .05) were found in the per-examination for the sensitivity of 18F-FDG PET/CT (0.80) compared to wUS (0.63) and pUS (0.61), and the specificity of 18F-FDG PET/CT (0.96) compared to wUS (0.98) and aUS (0.99). In the PLA, there were significant differences in sensitivity and specificity for 18F-FDG PET/CT (0.83, 0.91) compared to wUS (0.61, 0.98), pUS (0.60, 0.98), and aUS (0.61, 0.99). CONCLUSION: 18F-FDG PET/CT is preferable to US for detecting both lymph node and abdominal metastases.


Assuntos
Fluordesoxiglucose F18 , Melanoma , Masculino , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Estudos Retrospectivos , Tomografia por Emissão de Pósitrons/métodos , Melanoma/diagnóstico por imagem , Melanoma/patologia , Sensibilidade e Especificidade , Poliésteres , Supuração , Estadiamento de Neoplasias , Compostos Radiofarmacêuticos , Melanoma Maligno Cutâneo
15.
PLoS Genet ; 18(10): e1010420, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36223338

RESUMO

The Musashi family of RNA-binding proteins controls several biological processes including stem cell maintenance, cell division and neural function. Previously, we demonstrated that the C. elegans Musashi ortholog, msi-1, regulates forgetting via translational repression of the Arp2/3 actin-branching complex. However, the mechanisms controlling MSI-1 activity during the regulation of forgetting are currently unknown. Here we investigated the effects of protein phosphorylation on MSI-1 activity. We showed that MSI-1 function is likely controlled by alterations of its activity rather than its expression levels. Furthermore, we found that MSI-1 is phosphorylated and using mass spectrometry we identified MSI-1 phosphorylation at three residues (T18, S19 and S34). CRISPR-based manipulations of MSI-1 phosphorylation sites revealed that phosphorylation is necessary for MSI-1 function in both short- and long-term aversive olfactory associative memory. Thus, our study provides insight into the mechanisms regulating memory-related MSI-1 activity and may facilitate the development of novel therapeutic approaches.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Complexo 2-3 de Proteínas Relacionadas à Actina/metabolismo , Actinas/metabolismo , Animais , Caenorhabditis elegans/metabolismo , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Fosforilação , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo
16.
Clin Hemorheol Microcirc ; 82(2): 125-139, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35811511

RESUMO

BACKGROUND: Edema and subjective leg complaints (e.g. pain, heaviness) after long standing or sitting, are defined as orthostatic leg complaints or occupational edema. Compression hosiery should help to prevent or decrease those symptoms. OBJECTIVE: Assess the effects on leg discomforts and leg volume and wearing comfort in two medical below-knee compression stocking types (A vs. B) with an interface pressure of 18 -20 mmHg and a below-knee-low-pressure support stocking (LPSS) with an interface pressure of 8-10mmHg (C). METHODS: Two different types of below-knee medical compression stockings and a LPSS were examined in this randomized, blinded, crossover trial in volunteers having leg discomforts and edema after being in an upright position during the day. Participants were divided into two cohorts, and each type of stocking was worn for three consecutive days in one week with a subsequent washout phase. The assessment of effects and wearing comfort was ascertained by questionnaires. Volume changes in the lower leg were measured with the Bodytronic 600® (Bauerfeind AG, Zeulenroda, Germany). RESULTS: A significant reduction of lower leg volume (mean stocking A: 204.7 ml; mean stocking B: 153.5 ml; mean stocking C: 48.2 ml) and a significant reduction of the life-quality dimension leg-complaints (p < 0.0001) was achieved by all three types of stockings. Compared to the LPSS both compression stockings decreased the lower leg volume significantly more (p < 0.001) and had a significant better fit (p < 0.001). CONCLUSION: Below-knee medical compression stockings with an interface pressure 18-21mmHg and LPSS with an interface pressure of 8-10 mmHg reduce significantly occupational orthostatic edema and leg discomforts which are due to long standing and sitting activities.


Assuntos
Perna (Membro) , Meias de Compressão , Humanos , Edema/terapia , Extremidade Inferior , Qualidade de Vida
17.
Brain Sci ; 12(7)2022 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-35884646

RESUMO

Background: Comprehensive geriatric care (CGC) is a multidisciplinary approach developed to meet the needs of older patients. Electroencephalography (EEG) provides valuable information for monitoring the cerebral function. As a surrogate, EEG findings may help to estimate the course of diseases as well as the treatment outcomes. Objectives: Therefore, the aim of the present study is to investigate EEG findings in older patients receiving CGC. Methods: Patients with an initial EEG in a geriatric unit between May 2019 and April 2020 and treated using the CGC approach were analyzed. EEG abnormalities were defined as generalized (diffuse) background slowing and/or intermittent/persistent focal slowing and/or epileptiform discharges. Assessment results for the Barthel index (BI), Tinetti Balance and Gait test (TBGT), and Timed Up and Go test (TUG) were analyzed in relation to the presence of EEG abnormalities. Results: The study included 398 patients (mean age: 83.0 ± 6.57 years, 69.3% were female). Abnormal EEG patterns were found in 94 (23.6%) patients. Patients with EEG abnormalities had a mean age of 83.4 years versus a mean of 82.8 years in those without (p = 0.451). Based on all calculated scores, the majority of the patients improved after CGC, with a tendency to higher-grade improvements in those without EEG abnormalities (BI: 86.2% vs. 75.5%, p = 0.024; TUG: 53.3% vs. 31.9%, p < 0.001); for TBGT, only a gradual difference was detected (TBGT: 79.9% vs. 71.3%, p = 0.088). The presence of EEG abnormalities was associated with the parameters dementia (36.2% vs. 22.4%, p = 0.010), known epilepsy/seizure (19.1% vs. 5.9%, p < 0.001), structural brain lesion (47.9% vs. 19.7%, p < 0.001), and delirium (9.6% vs. 3.6%, p = 0.030) during hospitalization. Conclusions: We found EEG abnormalities in almost a quarter of the patients treated in the geriatric unit. In older patients, the presence of EEG abnormalities is associated with lower improvements after CGC.

18.
J Cardiovasc Electrophysiol ; 33(8): 1757-1766, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35578015

RESUMO

INTRODUCTION: Catheter contact is a key determinant for lesion size in radiofrequency catheter ablation (RFA). Monitoring of contact force (CF) during RFA has been shown to improve efficacy of RFA in experimental settings as well as in adult patients. Coronary artery narrowing after RFA has been described in experimental settings as well as in children and adults and may be dependent from catheter contact. The value of CF monitoring concerning these issues has not been systematically studied yet. Value of high versus low CF during RFA in piglets was studied to assess lesion size and potential coronary artery involvement mimicking RFA in small children. METHODS: RFA with continuous CF monitoring was performed in 24 piglets (median weight 18.5 kg) using a 7 F TactiCath Quartz radiofrequency (RF) ablation catheter (Abbott). A total of 7 lesions were induced in each animal applying low (10-20 g) or high (40-60 g) CF. RF energy was delivered with a target temperature of 65°C at 30 W for 30 s. Coronary angiography was performed prior and immediately after RF application. Animals were assigned to repeat coronary angiography followed by heart removal after 48 h (n = 12) or 6 months (n = 12). Lesions with surrounding myocardium were excised, fixated, and stained. Lesion volumes were measured by microscopic planimetry. RESULTS: A total of 148 RF lesions were identified in the explanted hearts. Only in the subset of lesions at the AV annulus 6 month after ablation, lesion size and number of lesions exhibiting transmural extension were higher in the high CF group compared to low CF. In all other locations CF had no impact on lesion size and mural extension after 48 h as well as after 6 months. Additional parameters such as lesion size index and force time integral were also not related to lesion size. Coronary artery damage was present in two animals after 48 h and in one after 6 months and was not related to CF. CONCLUSION: In our experimental setting, lesion size in piglets was not related to catheter CF. Transmural extension of the RF lesions involving the layers of the coronary arteries was frequently noted irrespective of CF. Coronary artery narrowing was present in 3/24 animals and was not related to CF. In infants and toddlers, low CF (10-20 g) may be of adequate effect. Impact of CF monitoring during conventional RF ablation in children requires further investigation.


Assuntos
Ablação por Cateter , Ablação por Radiofrequência , Animais , Ablação por Cateter/efeitos adversos , Catéteres , Coração , Humanos , Miocárdio/patologia
20.
J Dtsch Dermatol Ges ; 20(5): 597-609, 2022 05.
Artigo em Inglês | MEDLINE | ID: mdl-35429131

RESUMO

BACKGROUND: The basis for adequate psycho-oncological care is the identification of patients with psychosocial support needs. The German Working Group for Psychooncology also recommends the Hornheider Screening Instrument (HSI) for this purpose. The question, "Is anyone in your family particularly burdened by the hospital stay?" is intended to capture disease-related family stress. But is this item equally suitable for outpatients and inpatients? The study objective was to examine how replacing the original item affects the test performance of this modified version of the HSI and the frequency of psychosocial stress. PATIENTS AND METHODS: 92 outpatients and 98 inpatients with skin tumors assessed their psychosocial situation using different questionnaires. RESULTS: Compared to inpatients, less than half as many outpatients answered the item in the affirmative. If the question was replaced by: "Is someone in your family particularly burdened by your disease or the course of the disease?" this setting-related difference did not arise. The "Alternative item" and the "Modified version of the HIS" (HSI-MV) proved to be superior to the original item and the original HSI with regard to all examined criteria. CONCLUSIONS: The HSI-MV can be used as a reliable and valid instrument for the systematic assessment of psychosocial care needs in outpatient and inpatient settings. Depending on care capacity, a threshold of ≥ 5 or ≥ 4 is appropriate. In addition to screening, the desire for support should be enquired.


Assuntos
Pacientes Ambulatoriais , Neoplasias Cutâneas , Humanos , Pacientes Internados , Psicometria , Reprodutibilidade dos Testes , Neoplasias Cutâneas/diagnóstico , Neoplasias Cutâneas/psicologia , Inquéritos e Questionários
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