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1.
Proc Natl Acad Sci U S A ; 121(15): e2320484121, 2024 Apr 09.
Artículo en Inglés | MEDLINE | ID: mdl-38557183

RESUMEN

Ethnographic records show that wooden tools played a pivotal role in the daily lives of hunter-gatherers including food procurement tools used in hunting (e.g., spears, throwing sticks) and gathering (e.g. digging sticks, bark peelers), as well as, domestic tools (e.g., handles, vessels). However, wood rarely survives in the archeological record, especially in Pleistocene contexts and knowledge of prehistoric hunter-gatherer lifeways is strongly biased by the survivorship of more resilient materials such as lithics and bones. Consequently, very few Paleolithic sites have produced wooden artifacts and among them, the site of Schöningen stands out due to its number and variety of wooden tools. The recovery of complete wooden spears and throwing sticks at this 300,000-y-old site (MIS 9) led to a paradigm shift in the hunter vs. scavenger debate. For the first time and almost 30 y after their discovery, this study introduces the complete wooden assemblage from Schöningen 13 II-4 known as the Spear Horizon. In total, 187 wooden artifacts could be identified from the Spear Horizon demonstrating a broad spectrum of wood-working techniques, including the splitting technique. A minimum of 20 hunting weapons is now recognized and two newly identified artifact types comprise 35 tools made on split woods, which were likely used in domestic activities. Schöningen 13 II-4 represents the largest Pleistocene wooden artifact assemblage worldwide and demonstrates the key role woodworking had in human evolution. Finally, our results considerably change the interpretation of the Pleistocene lakeshore site of Schöningen.


Asunto(s)
Artefactos , Armas , Humanos , Huesos , Arqueología , Madera
2.
Eur J Med Chem ; 254: 115386, 2023 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-37094450

RESUMEN

The modulatory interactions between neurotensin (NT) and the dopaminergic neurotransmitter system in the brain suggest that NT may be associated with the progression of Parkinson's disease (PD). NT exerts its neurophysiological effects by interactions with the human NT receptors type 1 (hNTS1) and 2 (hNTS2). Therefore, both receptor subtypes are promising targets for the development of novel NT-based analogs for the treatment of PD. In this study, we used a virtually guided molecular modeling approach to predict the activity of NT(8-13) analogs by investigating the docking models of ligands designed for binding to the human NTS1 and NTS2 receptors. The importance of the residues at positions 8 and/or 9 for hNTS1 and hNTS2 receptor binding affinity was experimentally confirmed by radioligand binding assays. Further in vitro ADME profiling and in vivo studies revealed that, compared to the parent peptide NT(8-13), compound 10 exhibited improved stability and BBB permeability combined with a significant enhancement of the motor function and memory in a mouse model of PD. The herein reported NTS1/NTS2 dual-specific NT(8-13) analogs represent an attractive tool for the development of therapeutic strategies against PD and potentially other CNS disorders.


Asunto(s)
Neurotensina , Enfermedad de Parkinson , Animales , Humanos , Ratones , Dopamina , Ligandos , Neurotensina/farmacología , Neurotensina/metabolismo , Enfermedad de Parkinson/tratamiento farmacológico , Unión Proteica , Receptores de Neurotensina/metabolismo
3.
Science ; 380(6641): 178-187, 2023 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-37053338

RESUMEN

Venous thromboembolism (VTE) comprising deep venous thrombosis and pulmonary embolism is a major cause of morbidity and mortality. Short-term immobility-related conditions are a major risk factor for the development of VTE. Paradoxically, long-term immobilized free-ranging hibernating brown bears and paralyzed spinal cord injury (SCI) patients are protected from VTE. We aimed to identify mechanisms of immobility-associated VTE protection in a cross-species approach. Mass spectrometry-based proteomics revealed an antithrombotic signature in platelets of hibernating brown bears with heat shock protein 47 (HSP47) as the most substantially reduced protein. HSP47 down-regulation or ablation attenuated immune cell activation and neutrophil extracellular trap formation, contributing to thromboprotection in bears, SCI patients, and mice. This cross-species conserved platelet signature may give rise to antithrombotic therapeutics and prognostic markers beyond immobility-associated VTE.


Asunto(s)
Plaquetas , Proteínas del Choque Térmico HSP47 , Hipocinesia , Traumatismos de la Médula Espinal , Ursidae , Tromboembolia Venosa , Animales , Humanos , Ratones , Fibrinolíticos/uso terapéutico , Embolia Pulmonar/tratamiento farmacológico , Embolia Pulmonar/etnología , Embolia Pulmonar/metabolismo , Factores de Riesgo , Traumatismos de la Médula Espinal/complicaciones , Ursidae/metabolismo , Tromboembolia Venosa/etiología , Tromboembolia Venosa/metabolismo , Hipocinesia/complicaciones , Proteínas del Choque Térmico HSP47/metabolismo , Plaquetas/metabolismo
4.
Spine (Phila Pa 1976) ; 48(3): 164-171, 2023 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-36607627

RESUMEN

STUDY DESIGN: Multicenter retrospective analysis of routinely collected data. OBJECTIVE: The underlying aim of this study was to identify potential treatment-related risk factors for odontoid fracture nonunion while accounting for known patient- and injury-related risk factors. SUMMARY OF BACKGROUND DATA: Type II and III odontoid fractures represent the most common cervical spine fracture in elderly patients and are associated with a relatively high nonunion rate. The management of odontoid fractures is controversial and treatment strategies range from conservative treatment to extensive surgical stabilization and fusion. METHODS: A total of 415 individuals who sustained odontoid fracture and were treated in either of four tertiary referral centers in Austria and Germany were included in the study. We included the following potential contributing factors for fracture nonunion in cross-validated extreme gradient boosted (XGBoost) and binary logistic regression models: age, gender, fracture displacement, mechanism of injury (high vs. low energy), fracture classification (Anderson II vs. III), presence of comorbidities (Charlson comorbidity index), and treatment (conservative, anterior screw fixation with one or two screws, posterior C1/C2 spondylodesis, cervico-occipital C0-C4 fusion). RESULTS: In our cohort, 187 (45%) had radiologically confirmed odontoid nonunion six months postinjury. The odds for nonunion increase significantly with age, and are lower in type III compared to type II fractures. Also, odds for nonunion are significantly lower in posterior C1/C2 spondylodesis, and C0-C4 fusion compared to conservative treatment. Importantly, odds are not statistically significantly lower in the group treated with anterior screw fixation compared to conservative treatment. The factors gender, fracture displacement, mechanism of injury, and the presence of comorbidities did not produce significant odds. CONCLUSION: Higher age, type II fractures, and conservative treatment are the main risk factors for odontoid nonunion. Anterior screw fixation did not differ significantly from conservative treatment in terms of fracture union. LEVEL OF EVIDENCE: 3.


Asunto(s)
Fracturas Óseas , Apófisis Odontoides , Fracturas de la Columna Vertebral , Fusión Vertebral , Humanos , Anciano , Apófisis Odontoides/diagnóstico por imagen , Apófisis Odontoides/cirugía , Apófisis Odontoides/lesiones , Estudios Retrospectivos , Fijación Interna de Fracturas , Fracturas de la Columna Vertebral/diagnóstico por imagen , Fracturas de la Columna Vertebral/epidemiología , Fracturas de la Columna Vertebral/cirugía , Factores de Riesgo , Aprendizaje Automático , Resultado del Tratamiento
5.
Z Psychosom Med Psychother ; 69(4): 369-382, 2023 Dec.
Artículo en Alemán | MEDLINE | ID: mdl-38214019

RESUMEN

Objectives: Psychic perceptions are at the core of psychotherapeutic processes and modifiable by certain psychopharmacologic agents including antidepressants and cyclooxygenase (COX) inhibitors like acetylsalicylic acid (ASA). Methods: We analyzed the medical records of 208 participants, and used the weekly mean dosages and the number of weeks in therapy to predict ward experience (Stationserfahrungsbogen) and symptom burden (symptom-check list 90-R) by means of linear regression analyses and four repeated measures. Results: Time predicted symptom relief. ASA signified a more favorable ward experience and a trend towards less suffering. Antidepressants did not predict symptom burden or ward experience, except for amitriptyline's inverse relationship with process perception. Discussion: Regarding process perception and therapy outcome, amitriptyline might have unfavorable effects at dose reductions, whereas COX-inhibition could be beneficial at higher dosages. Similar findings have already been described with regard to COX-inhibition in depression and schizophrenia.


Asunto(s)
Aspirina , Ácido Salicílico , Humanos , Aspirina/efectos adversos , Amitriptilina/efectos adversos , Pacientes Internos , Antidepresivos/efectos adversos , Trastornos Psicofisiológicos , Procesos Psicoterapéuticos , Percepción
6.
J Clin Med ; 11(18)2022 Sep 19.
Artículo en Inglés | MEDLINE | ID: mdl-36143137

RESUMEN

INTRODUCTION: Chronic pain is a multifaceted disorder genuinely entangled with psychic and psychosomatic symptoms, which are typically involved in the processes of chronification. The impingement syndrome of the shoulder is no exception to this rule, but several studies have shown respective peculiarities among those with pain and impingement of the shoulder. Notably, chronic pain is a lateralized experience, and, similarly, its psychosomatic correlates may be attached to the hemispheres functionally. AIM: The present review therefore gives an overview of the respective findings, with regard not only to psychopathology, but also to personality factors and psychologic trauma, since the latter are reportedly associated with chronic pain. Moreover, we acknowledge symmetry as a possible pathogenic factor. METHODS: This narrative review followed the current standards for conducting narrative studies. Based on prior findings, our research strategy included the relevance of psychotraumatologic and symmetrical aspects, as well as comorbidity. We retrieved the relevant literature reporting on the impact of psychopathology as well as personality features on shoulder pain, as published up to January 2022 from the Medline database (1966-2022). Study selecton: We included numerous studies, and considered the contextual relevance of studies referring to the neuropsychosomatics of chronic pain. RESULTS: Pain-specific fears, depression, and anxiety are important predictors of shoulder pain, and the latter is generally overrepresented in those with trauma and PTSD. Moreover, associations of shoulder pain with psychological variables are stronger as regards surgical therapies as compared to conservative ones. This may point to a specific and possibly trauma-related vulnerability for perioperative maladaptation. Additionally, functional hemispheric lateralization may explain some of those results given that limb pain is a naturally lateralized experience. Not least, psychosocial risk factors are shared between shoulder pain and its physical comorbidities (e.g., hypertension), and the incapacitated state of the shoulder is a massive threat to the function of the human body as a whole. CONCLUSIONS: This review suggests the involvement of psychosomatic and psychotraumatologic factors in shoulder impingement-related chronic pain, but the inconclusiveness and heterogeneity of the literature in the field is possibly suggestive of other determinants such as laterality.

7.
J Pharm Biomed Anal ; 219: 114910, 2022 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-35779354

RESUMEN

In 2018, high levels of the IARC class IIA carcinogen N-nitrosodimethylamine (NDMA) were analytically verified in the active pharmaceutical ingredient (API) valsartan, resulting in extensive regulatory action on angiotensin-II-receptor antagonists and recall of finished drug products by the pharmaceutical industry to ensure patient safety. The root cause of contamination was the unintended reaction of common reagents utilized during drug synthesis. This lead to serious effects on drug quality and immediate regulatory action. Thus, routine analysis of drug product contents are inevitable and necessitate thoroughly performed work up procedures of the product as well as adequate validated analytical methods. The nature of N-nitrosamines (NA), ranging from small, semi-volatile compounds up to highly polar molecules, effort sophisticated requirements in terms of instrumental analysis. Up today, gas as well as liquid chromatographic devices coupled to mass spectrometers are the most widespread systems for analysis. Gas chromatographic - mass spectrometric (GC-MS) systems, obviously superior towards liquid chromatography - mass spectrometry (LC-MS) for detecting small volatile compounds like NDMA, reach their limits for broadly designed studies including polar or acidic NA. In this study, a complementary and highly sensitive approach by means of liquid chromatography - tandem mass spectrometry (LC-MS/MS) is presented, including detection of 13 NA deduced from major classes of secondary amines. Thereby, the fully validated approach was performed in accordance to ICH and European Medicines Agency (EMA) guidelines. Quantitative proof-of-concept measurements with various APIs and market authorized tablets as representative drug formulations conclude applicability for further presumably contaminated substances. The approach employs organic or inorganic extraction steps with solid phase extraction (SPE). The limit of detection for the most prominent NA, NDMA and N-diethylnitrosamine (NDEA), were both 0.025 parts-per-billion (ppb) per matrix, respectively.


Asunto(s)
Cromatografía Liquida/métodos , Contaminación de Medicamentos/prevención & control , Nitrosaminas/análisis , Preparaciones Farmacéuticas/química , Espectrometría de Masas en Tándem/métodos , Daño del ADN , Dimetilnitrosamina/análisis , Dimetilnitrosamina/toxicidad , Humanos , Nitrosaminas/toxicidad , Preparaciones Farmacéuticas/normas
8.
iScience ; 25(4): 104076, 2022 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-35309727

RESUMEN

SARS-CoV-2 Omicron is the first pandemic variant of concern exhibiting an abrupt accumulation of mutations particularly in the receptor-binding domain that is a critical target of vaccination induced and therapeutic antibodies. Omicron's mutations did only marginally affect the binding of ACE2, and the two antibodies Sotrovimab and CR3022 but strongly impaired the binding of Casirivimab and Imdevimab. Moreover, as compared with Wuhan, there is reduced serum reactivity and a pronounced loss of competitive surrogate virus neutralization (sVN) against Omicron in naïve vaccinees and in COVID-19 convalescents after infection and subsequent vaccination. Finally, although the booster vaccination response conferred higher titers and better sVN, the effect was nonetheless significantly lower compared with responses against Wuhan. Overall, our data suggest that the antigenicity of Omicrons receptor binding motive has largely changed but antibodies such as Sotrovimab targeting other conserved sites maintain binding and therefore hold potential in prophylaxis and treatment of Omicron-induced COVID-19.

9.
J Clin Med ; 11(4)2022 Feb 18.
Artículo en Inglés | MEDLINE | ID: mdl-35207366

RESUMEN

INTRODUCTION: Total knee arthroplasty (TKA) bears a potential of rendering patients unsatisfied with the operation as a result of negative affectivity related to osteoarthritis and TKA. Not only is pain a lateralized experience, but negative affect and other psychosomatic correlates of pain might also be processed on grounds of lateralization. Lateralization in this context is likely linked to the amygdalae, which display differential left/right patterns of association with psychopathology. What is noteworthy is that osteoarthritis itself is linked not only to negative effects but also to childhood abuse. METHOD: The present study tests lateralization of psychosomatic correlates of knee-pain using the brief symptom inventory-18 (BSI-18), the dissociative experiences scale (FDS-20), the pain catastrophizing scale (PCS), the Tampa scale of kinesiophobia (TSK), the childhood trauma screener (CTS) and WOMAC. More precisely, we were interested in predicting the side of operations by means of the above-mentioned constructs using binary logistic regression, based on 150 participants (78 left knees) awaiting TKA for knee-osteoarthritis. RESULTS: Somatization (p = 0.003), childhood abuse (p = 0.04) and pain-catastrophizing (p = 0.04) predicted operations on the right side. Anxiety (p = 0.001) and kinesiophobia (p = 0.002) predicted operations on the left side. CONCLUSIONS: Knee-pain may be differentially modulated by its psychosomatic correlates as a result of lateralization and corresponding patterns of psychosomatic reagibility.

10.
Int J Eat Disord ; 55(2): 285-287, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35014056

RESUMEN

Burnette et al. reported a study that they sought to undertake to validate common eating disorder questionnaires in sexual and gender minorities. The researchers took advantage of the online recruitment platform Amazon Mechanical Turk (MTurk). Contrary to their expectations, the study proved not feasible due to invalid answering. Thus, Burnette et al. raise concerns against the trustworthiness of crowd-sourced data that may be undermined by financial interests and other kinds of motivations. Our commentary highlights the potential of the COVID-19 pandemic to inflate especially those intentions, which are monetary. Against the background of the COVID-19 pandemic, a further problem seems to be that the anonymity of online crowd sourcing platforms might tempt participants to provide inconsistent answers, possibly reflecting tendencies of reactance. The reported pattern of paradoxical responses in Burnette et al.'s work does not reflect malingering; rather we believe that the study might have served some participants as an outlet for negative emotions. We discuss mechanisms of quality control and highlight the lack of interpersonal interaction associated with online data collections.


Asunto(s)
COVID-19 , Colaboración de las Masas , Trastornos de Alimentación y de la Ingestión de Alimentos , Humanos , Pandemias , SARS-CoV-2 , Encuestas y Cuestionarios
11.
Pharmaceuticals (Basel) ; 14(11)2021 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-34832903

RESUMEN

Heat sterilization of glucose solutions can lead to the formation of various glucose degradation products (GDPs) due to oxidation, hydrolysis, and dehydration. GDPs can have toxic effects after parenteral administration due to their high reactivity. In this study, the application of the F0 concept to modify specific time/temperature models during heat sterilization and their influence on the formation of GDPs in parenteral glucose solutions was investigated using high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glucose solutions (10%, w/v) were autoclaved at 111 °C, 116 °C, and 121 °C for different durations. The GDPs glyoxal, methylglyoxal, glucosone, 3-deoxyglucosone/3-deoxygalactosone, 3,4-dideoxyglucosone-3-ene, and 5-hydroxymethylfurfural were quantified after derivatization with o-phenylenediamine by an optimized LC-MS/MS method. For all GDPs, the limit of detection was <0.078 µg/mL, and the limit of quantification was <0.236 µg/mL. The autoclaving time of 121 °C and 15 min resulted in the lowest levels of 3-DG/3-DGal and 5-HMF, but in the highest levels of GO and 2-KDG. The proposed LC-MS/MS method is rapid and sensitive. So far, only 5-HMF concentrations are limited by the regulatory authorities. Our results suggest reconsidering the impurity limits of various GDPs, especially the more toxic ones such as GO and MGO, by the Pharmacopoeias.

12.
Scand J Pain ; 21(2): 238-246, 2021 04 27.
Artículo en Inglés | MEDLINE | ID: mdl-34387954

RESUMEN

BACKGROUND: Surgery may possibly be undermined by psychologic, psychiatric and psychosomatic problems, as long as these problems interfere with a patient's capacity to cope with surgery adaptively. Recent studies have shown that interpersonal trauma, e.g. abuse or neglect, and its correlates are involved in the adaptation to surgery. This observation is heuristically coherent, given the respective traumatization is an interpersonal event occurring in a relationship. Notably, surgery inevitably leads to the violation of physical boundaries within a doctor-patient relationship. Based on the principles of psycho-traumatologic thinking, such a constellation is deemed qualified to activate posttraumatic symptoms in the traumatized. METHOD: The present topical review summarizes the respective findings which point to a subgroup of patients undergoing surgery, in whom difficulty bearing tension and confiding in others may cause adaptive problems relevant to surgery. Although this theorizing is empirically substantiated primarily with respect to total knee arthroplasty (TKA), a pubmed-research reveals psychopathologic distress to occur prior to surgery beyond TKA. Likewise, posttraumatic distress occurs in large numbers in the context of several operations, including cardiac, cancer and hernia surgery. CONCLUSION: Aspects of psychological trauma may be linked to the outcomes of general surgery, as well, e.g. biliary, hernia or appendix surgery. The mechanisms possibly involved in this process are outlined in terms of a hierarchical organization of specific anxiety and negative affect as well as in terms of psychodynamics which imply the unconscious action of psychologic defenses at their core. IMPLICATIONS: Not least, we encourage the screening for trauma and its correlates including defenses prior to general surgery in order to identify surgical candidates at risk of, e.g. chronic postoperative pain, before the operation.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Relaciones Médico-Paciente , Adaptación Psicológica , Ansiedad , Humanos , Dolor Postoperatorio
13.
PLoS One ; 16(7): e0253811, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34214128

RESUMEN

During heat sterilization of glucose solutions, a variety of glucose degradation products (GDPs) may be formed. GDPs can cause cytotoxic effects after parenteral administration of these solutions. The aim of the current study therefore was to develop a simple and quick high-performance thin-layer chromatography (HPTLC) method by which the major GDPs can be identified and (summarily) quantified in glucose solutions for parenteral administration. All GDPs were derivatized with o-phenylenediamine (OPD). The resulting GDP derivatives (quinoxalines) were applied to an HPTLC plate. After 20 minutes of chamber saturation with the solvent, the HPTLC plate was developed in a mixture of 1,4-dioxane-toluene-glacial acetic acid (49:49:2, v/v/v), treated with thymol-sulfuric acid spray reagent, and heated at 130°C for 10 minutes. Finally, the GDPs were quantified by using a TLC scanner. For validation, the identities of the quinoxaline derivatives were confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Glyoxal (GO)/methylglyoxal (MGO) and 3-deoxyglucosone (3-DG)/3-deoxygalactosone (3-DGal) could be identified and quantified in pairs, glucosone (2-KDG), 5-hydroxymethylfurfural (5-HMF), and 3,4-dideoxyglucosone-3-ene (3,4-DGE) each individually. For 2-KDG, the linearity of the method was demonstrated in the range of 1-50 µg/mL, for 5-HMF and 3,4-DGE 1-75 µg/mL, for GO/MGO 2-150 µg/mL, and for 3-DG/3-DGal 10-150 µg/mL. All GDPs achieved a limit of detection (LOD) of 2 µg/mL or less and a limit of quantification (LOQ) of 10 µg/mL or less. R2 was 0.982 for 3.4-DGE, 0.997 for 5-HMF, and 0.999 for 2-KDG, 3-DG/3-DGal, and GO/MGO. The intraday precision was between 0.4 and 14.2% and the accuracy, reported as % recovery, between 86.4 and 112.7%. The proposed HPTLC method appears to be an inexpensive, fast, and sufficiently sensitive approach for routine quantitative analysis of GDPs in heat-sterilized glucose solutions.


Asunto(s)
Estabilidad de Medicamentos , Glucosa/análisis , Calor/efectos adversos , Control de Calidad , Cromatografía en Capa Delgada , Glucosa/administración & dosificación , Glucosa/química , Glucosa/normas , Infusiones Parenterales/normas , Soluciones Farmacéuticas/administración & dosificación , Soluciones Farmacéuticas/análisis , Soluciones Farmacéuticas/química , Soluciones Farmacéuticas/normas , Esterilización/métodos , Espectrometría de Masas en Tándem
14.
Psychother Psychosom Med Psychol ; 71(8): 328-334, 2021 Aug.
Artículo en Alemán | MEDLINE | ID: mdl-33773519

RESUMEN

OBJECTIVE: Even after successful knee replacement, one in 5 patients complains of chronic pain. Previous studies suggest that surgical interventions trigger postoperative traumatic stress in some patients. The aim of this explorative study is to investigate whether postoperative dissociation occurs as a manifestation of postoperative traumatic stress after total knee replacement. In addition, it should be investigated whether these patients have more chronic postoperative pain 1 year postoperatively and to what extent the course of pain differs from the other patients. METHODS: 201 Patients who underwent primary knee TEP were studied. They answered questionnaires on knee pain (WOMAC) and dissociation (FDS-20) at 3 measurement points: 1 day preoperatively (T1), 10 weeks postoperatively (T2) and 1 year postoperatively (T3). RESULTS: Data from 145 patients could be analyzed. The incidence for postoperative dissociation is 8.3%. Not only do patients with postoperative dissociation report more chronic postoperative pain after 1 year (p=0,016), but also their postoperative pain levels decreases less than in the patients without postoperative dissociation (p=0,025). DISCUSSION: The findings provide evidence that postoperative dissociation occurs as a manifestation of postoperative traumatic stress after total knee replacement. Even if dissociation seems to be a defense mechanism for the regulation of overstraining affects in the short term, it is associated with more chronic postoperative pain in the long term. Furthermore, the patients with postoperative dissociation benefit less in a 1-year follow-up from total knee replacement in terms of pain reduction. CONCLUSION: Strategies to reduce dissociation could lead to better results after knee TEP implementation and should be investigated in future intervention studies.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Dolor Crónico , Artroplastia de Reemplazo de Rodilla/efectos adversos , Dolor Crónico/epidemiología , Dolor Crónico/etiología , Humanos , Dimensión del Dolor , Dolor Postoperatorio/epidemiología , Dolor Postoperatorio/etiología , Encuestas y Cuestionarios , Resultado del Tratamiento
15.
Infection ; 49(1): 75-82, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32827125

RESUMEN

OBJECTIVE: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic challenges national health systems and the global economy. Monitoring of infection rates and seroprevalence can guide public health measures to combat the pandemic. This depends on reliable tests on active and former infections. Here, we set out to develop and validate a specific and sensitive enzyme linked immunosorbent assay (ELISA) for detection of anti-SARS-CoV-2 antibody levels. METHODS: In our ELISA, we used SARS-CoV-2 receptor-binding domain (RBD) and a stabilized version of the spike (S) ectodomain as antigens. We assessed sera from patients infected with seasonal coronaviruses, SARS-CoV-2 and controls. We determined and monitored IgM-, IgA- and IgG-antibody responses towards these antigens. In addition, for a panel of 22 sera, virus neutralization and ELISA parameters were measured and correlated. RESULTS: The RBD-based ELISA detected SARS-CoV-2-directed antibodies, did not cross-react with seasonal coronavirus antibodies and correlated with virus neutralization (R2 = 0.89). Seroconversion started at 5 days after symptom onset and led to robust antibody levels at 10 days after symptom onset. We demonstrate high specificity (99.3%; N = 1000) and sensitivity (92% for IgA, 96% for IgG and 98% for IgM; > 10 days after PCR-proven infection; N = 53) in serum. CONCLUSIONS: With the described RBD-based ELISA protocol, we provide a reliable test for seroepidemiological surveys. Due to high specificity and strong correlation with virus neutralization, the RBD ELISA holds great potential to become a preferred tool to assess thresholds of protective immunity after infection and vaccination.


Asunto(s)
Anticuerpos Antivirales/sangre , Antígenos Virales/inmunología , COVID-19/diagnóstico , Ensayo de Inmunoadsorción Enzimática/normas , Pruebas de Neutralización/normas , SARS-CoV-2/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Anticuerpos Neutralizantes/sangre , Antígenos Virales/química , COVID-19/sangre , COVID-19/inmunología , COVID-19/virología , Estudios Transversales , Humanos , Sueros Inmunes/química , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Inmunoglobulina M/sangre , Dominios Proteicos , Sensibilidad y Especificidad , Glicoproteína de la Espiga del Coronavirus/química
16.
Hum Brain Mapp ; 42(3): 797-810, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33151031

RESUMEN

Dysfunctions in bottom-up emotion processing (EP), as well as top-down emotion regulation (ER) are prominent features in pathophysiology of major depressive disorder (MDD). Nonetheless, it is not clear whether EP- and ER-related areas are regionally and/or connectively disturbed in MDD. In addition, it is yet to be known how EP- and ER-related areas are interactively linked to regulatory behavior, and whether this interaction is disrupted in MDD. In our study, regional amplitude of low frequency fluctuations (ALFF) and whole-brain functional connectivity (FC) of meta-analytic-driven EP- and ER-related areas were compared between 32 healthy controls (HC) and 20 MDD patients. Then, we aimed to investigate whether the EP-related areas can predict the ER-related areas and regulatory behavior in both groups. Finally, the brain-behavior correlations between the EP- and ER-related areas and depression severity were assessed. We found that: (a) affective areas are regionally and/or connectively disturbed in MDD; (b) EP-ER interaction seems to be disrupted in MDD; overburden of emotional reactivity in amygdala may inversely affect cognitive control processes in prefrontal cortices, which leads to diminished regulatory actions. (c) Depression severity is correlated with FC of affective areas. Our findings shed new lights on the neural underpinning of affective dysfunctions in depression.


Asunto(s)
Síntomas Afectivos/fisiopatología , Amígdala del Cerebelo/fisiopatología , Corteza Cerebral/fisiopatología , Conectoma/métodos , Trastorno Depresivo Mayor/fisiopatología , Regulación Emocional/fisiología , Adulto , Síntomas Afectivos/diagnóstico por imagen , Síntomas Afectivos/etiología , Amígdala del Cerebelo/diagnóstico por imagen , Corteza Cerebral/diagnóstico por imagen , Trastorno Depresivo Mayor/complicaciones , Trastorno Depresivo Mayor/diagnóstico por imagen , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad
17.
Eur J Neurosci ; 52(3): 3047-3060, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32239708

RESUMEN

The cingulate cortex is involved in emotion recognition/perception and regulation. Rostral and caudal subregions belong to different brain networks with distinct roles in affective perception. Despite recent accounts of the relevance of cingulate cortex glutamate (Glu) on blood-oxygen-level-dependent (BOLD) responses, the specificity of the subregional Glu levels during emotional tasks remains unclear. Seventy-two healthy participants (age = 27.33 ± 6.67, 32 women) performed an affective face-matching task and underwent magnetic resonance spectroscopy (MRS) at 7 Tesla. Correlations between the BOLD response during emotion perception and Glu concentration in the pregenual anterior cingulate cortex (pgACC) and anterior midcingulate cortex (aMCC) were compared on a whole-brain level. Post hoc specificity of the association with an affect was assessed. Lower Glu in the pgACC correlated with stronger activation differences between negative and positive faces in the left inferior and superior frontal gyrus (L IFG and L SFG). In contrast, lower Glu in the aMCC correlated with BOLD contrasts in the posterior cingulate cortex (PCC). Furthermore, negative face detection was associated with prolonged response time (RT). Our results demonstrate a subregion-specific involvement of cingulate cortex Glu in interindividual differences during viewing of affective facial expressions. Glu levels in the pgACC were correlated with frontal area brain activations, whereas Glu in the salience network component aMCC modulated responses in the PCC-precuneus. We show that region-specific metabolite mapping enables specific activation of different BOLD signals in the brain underlying emotional perception.


Asunto(s)
Reconocimiento Facial , Giro del Cíngulo , Adulto , Encéfalo , Mapeo Encefálico , Femenino , Ácido Glutámico , Humanos , Imagen por Resonancia Magnética , Adulto Joven
18.
J Pain Res ; 13: 49-55, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32021394

RESUMEN

BACKGROUND: TKA is a common treatment for arthropathies of the knee; however, its results are compromised by psychosocial equivalents of pain: prior research suggests persistent pain and dysfunction after TKA not only to be linked to psychological symptoms such as depression or anxiety but also to psychodynamic determinants of borderline personality, namely borderline personality organization. Osteoarthritis (OA) and Rheumatoid arthritis (RA), the main indications for TKA, are themselves linked to personality factors and disorders, e.g. borderline. The present study investigates the influence of borderline personality organization (BPO) on the outcomes of TKA one year postoperatively. METHODS: We studied 144 patients scheduled for primary TKA before and after the operation using the IPO-16 and the WOMAC for the assessment of knee pain and function. RESULTS: Non-parametric correlations were found between primitive defenses and knee-pain, not function. Linear regression showed prediction of knee pain and knee function by the preoperative WOMAC scores (p<0.01), whereas there was additional prediction of knee-pain by gender (p=0.03) and primitive defenses (p=0.04). DISCUSSION: The results suggest a psychodynamic mechanism of maladaptation after TKA apparently representing the bodily manifestations of fundamental psychic defenses.

19.
Spinal Cord ; 58(1): 70-77, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31312018

RESUMEN

STUDY DESIGN: Retrospective matched cohort study. OBJECTIVES: Assessing the influence of surgically managed grade 3 and 4 pressure ulcers (PU) in the acute phase after spinal cord injury (SCI) on the neurological and functional outcome after 1 year. SETTING: Specialized SCI-unit within a level 1 trauma center in Murnau, Germany. METHODS: We performed a retrospective matched cohort study. For every patient with acute SCI and a PU requiring surgery, we identified matched controls within our database in a 1:3 ratio. Matching criteria were: AIS-grade (American Spinal Injury Association Impairment Scale), neurological level and age. The scores of the SCIM-III (Spinal Cord Independence Measure) and the ISNCSCI (International Standards for Neurological Classification of Spinal Cord Injury) as well as the total length of stay (LOS) at the hospital were used as outcome parameters. We applied a stratified analysis using a conditional logistic regression to test for group differences in each outcome parameter of the study. RESULTS: In a 6-year period (2010-2015) 28 patients required flap surgery due to 3-4° PU in the acute phase after SCI. Of these patients, 15 had complete data sets according to the EMSCI (European Multicenter Study about Spinal Cord Injury) protocol. Patients with severe PUs during the acute SCI phase had a significantly impaired functional outcome. After 1 year the improvement of the SCIM score was significantly lower in the PU group compared to the control group (17.4 versus 30.5; p < 0.006). However, the change in AIS grade after 1 year was not significantly affected. The LOS was prolonged by a mean of 48 days in the PU group (p < 0.006). CONCLUSIONS: Severe PUs requiring surgery in the acute phase after SCI impair the functional outcome and increase LOS. Preventive measures should be applied to all acute SCI patients. Patients should be transferred to specialized SCI-centers as soon as possible.


Asunto(s)
Tiempo de Internación , Evaluación de Resultado en la Atención de Salud , Úlcera por Presión/etiología , Úlcera por Presión/cirugía , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/terapia , Enfermedad Aguda , Adulto , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos
20.
J Mech Behav Biomed Mater ; 101: 103434, 2020 01.
Artículo en Inglés | MEDLINE | ID: mdl-31542569

RESUMEN

BACKGROUND: For prosthetic knee joints of the hinged type, typically polyethylene (PE) flexion bushings are used between axis and femoral component to prevent metallic wear. Nevertheless, PE-wear can lead to periprosthetic osteolysis followed by aseptic loosening of the implant. Based on high creep and wear resistance carbon-fibre-reinforced polyether ether ketones (CFR-PEEKs) could provide an alternative material to ultra-high-molecular-weight polyethylene (UHMWPE) for this bearing type. METHODS: Flexion bushings of four different materials were investigated (CFR-PEEK pitch fibres, CFR-PEEK PAN fibres, virgin PEEK without carbon fibres and UHMWPE) using a bushing tester. For determination of the polymeric and metallic wear, gravimetric measurements and particle analyses were performed. RESULTS: The polymeric wear rates of CFR-PEEK PAN (6.657 ±â€¯0.714 mg/106 cycles) and CFR-PEEK pitch (32.085 ±â€¯2.748 mg/106 cycles) were significantly higher compared to the polymeric wear rates of virgin PEEK (0.764 ±â€¯0.283 mg/106 cycles) or UHMWPE (-0.015 ±â€¯0.011 mg/106 cycles) (p < .001). In addition, the metallic wear rates were significantly higher when using bushings made of CFR-PEEK PAN (3.373 ±â€¯0.214 mg/106 cycles) and CFR-PEEK pitch (3.604 ±â€¯0.355 mg/106 cycles), than when using bushings made of virgin PEEK (0.177 ±â€¯0.049 mg/106 cycles) or UHMWPE (0.031 ±â€¯0.011 mg/106 cycles) (p < .001). The mean particle size of the two CFR-PEEK groups was significantly smaller compared to the virgin PEEK and UHMWPE group (p < .001). CONCLUSION: According to these results, the clinical use of CFR-PEEK in combination with CoCr could lead to higher wear rates and this should be avoided. Virgin PEEK may still be considered as an alternative to UHMWPE to use it for flexion bushings in a hinged knee joint.


Asunto(s)
Fibra de Carbono/química , Cetonas/química , Articulación de la Rodilla , Prótesis de la Rodilla , Polietilenglicoles/química , Rotación , Benzofenonas , Pruebas Mecánicas , Tamaño de la Partícula , Polietileno/química , Polímeros
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