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1.
Nat Commun ; 14(1): 8371, 2023 Dec 15.
Article En | MEDLINE | ID: mdl-38102132

Quantum networks have the potential to transform secure communication via quantum key distribution and enable novel concepts in distributed quantum computing and sensing. Coherent quantum light generation at telecom wavelengths is fundamental for fibre-based network implementations, but Fourier-limited emission and subnatural linewidth photons have so far only been reported from systems operating in the visible to near-infrared wavelength range. Here, we use InAs/InP quantum dots to demonstrate photons with coherence times much longer than the Fourier limit at telecom wavelength via elastic scattering of excitation laser photons. Further, we show that even the inelastically scattered photons have coherence times within the error bars of the Fourier limit. Finally, we make direct use of the minimal attenuation in fibre for these photons by measuring two-photon interference after 25 km of fibre, demonstrating finite interference visibility for photons emitted about 100,000 excitation cycles apart.

3.
J Neural Transm (Vienna) ; 130(6): 863-873, 2023 06.
Article En | MEDLINE | ID: mdl-37165120

Dopamine agonists are an important component of Parkinson's therapy. When weighing up the various therapy options, therapy with levodopa has recently been increasingly preferred due to its stronger efficacy and the ostensibly lower rate of side effects. The advantage of the lower incidence of motor complications during therapy with dopamine agonists was neglected. The occurrence of side effects can be explained by the different receptor affinity to the individual dopaminergic and non-dopaminergic receptors of the individual dopamine agonists. However, the different affinity to individual receptors also explains the different effect on individual Parkinson symptoms and can, therefore, contribute to a targeted use of the different dopamine agonists. Since comparative studies on the differential effect of dopamine agonists have only been conducted for individual substances, empirical knowledge of the differential effect is of great importance. Therefore, the guidelines for the treatment of Parkinson's disease do not consider the differential effect of the dopamine agonists. The historical consideration of dopamine agonists within Parkinson's therapy deserves special attention to be able to classify the current discussion about the significance of dopamine agonists.


Drug-Related Side Effects and Adverse Reactions , Parkinson Disease , Humans , Dopamine Agonists/adverse effects , Parkinson Disease/drug therapy , Antiparkinson Agents/adverse effects , Levodopa/adverse effects
4.
J Cancer Res Clin Oncol ; 149(11): 9071-9083, 2023 Sep.
Article En | MEDLINE | ID: mdl-37171614

PURPOSE: The Oxathiazinane substance class is characterized by a high diversity of chemical structures yet to be fully investigated. Our research group recently proved that the 1.4.5-oxathiazine-4.4-dioxide, known as substance GP-2250, possesses antineoplastic properties as shown on pancreatic carcinoma. This current study aims to gain insights into the structure and activity relationship of a series of different Oxathiazinanes regarding their antineoplastic activity and the potential correlation with antibacterial activity. We investigated the newly synthesized Oxathiazinane derivatives: 2255, 2256, 2287, 2289, 2293 and 2296 in comparison to GP-2250. METHODS: The antineoplastic effect was evaluated in different cancer entities (breast, skin, pancreas and colon cancer cell lines) by viability, proliferation, and cell migration assays in vitro. Disc diffusion tests were performed on various bacteria strains to examine the antibacterial potential. Additionally, reactive oxygen species (ROS) assays were conducted to investigate mechanistic aspects. RESULTS: The substances GP-2250, 2293, 2289 and 2296 not only showed antineoplastic activity in four different cancer entities but also antibacterial effects, as tested on multiple bacteria strains including MRSA (Methicillin-resistant Staphylococcus aureus). Furthermore, these substances also induced high ROS levels up to 110% in the treated cancer cell lines compared to untreated control cells. These results indicate a correlation between an antineoplastic capacity and antibacterial properties of these derivatives. Both activities appear to be ROS driven. The Oxathiazinane derivatives 2255, 2256 and 2287 lacked both, antineoplastic and antibacterial activity. CONCLUSION: Thus, a comparable structure activity relationship became apparent for both the antineoplastic and antibacterial activity.


Antineoplastic Agents , Methicillin-Resistant Staphylococcus aureus , Humans , Methicillin-Resistant Staphylococcus aureus/metabolism , Reactive Oxygen Species/metabolism , Microbial Sensitivity Tests , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Bacteria , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry
5.
Mol Metab ; 72: 101714, 2023 06.
Article En | MEDLINE | ID: mdl-36966947

OBJECTIVE: Mice with global deletion of the transient receptor potential channel melastatin family member 8 (TRPM8) are obese, and treatment of diet-induced obese (DIO) mice with TRPM8 agonists decrease body weight. Whether TRPM8 signaling regulates energy metabolism via central or peripheral effects is unknow. Here we assessed the metabolic phenotype of mice with either Nestin Cre-mediated neuronal loss of TRPM8, or with deletion of TRPM8 in Advillin Cre positive sensory neurons of the peripheral nervous system (PNS). METHODS: Nestin Cre- and Advillin Cre-Trpm8 knock-out (KO) mice were metabolically phenotyped under chronic exposure to either chow or high-fat diet (HFD), followed by assessment of energy and glucose metabolism. RESULTS: At room temperature, chow-fed neuronal Trpm8 KO are obese and show decreased energy expenditure when acutely treated with the TRPM8 selective agonist icilin. But body weight of neuronal Trpm8 KO mice is indistinguishable from wildtype controls at thermoneutrality, or when mice are chronically exposed to HFD-feeding. In contrast to previous studies, we show that the TRPM8 agonist icilin has no direct effect on brown adipocytes, but that icilin stimulates energy expenditure, at least in part, via neuronal TRPM8 signaling. We further show that lack of TRPM8 in sensory neurons of the PNS does not lead to a metabolically relevant phenotype. CONCLUSIONS: Our data indicate that obesity in TRPM8-deficient mice is centrally mediated and likely originates from alterations in energy expenditure and/or thermal conductance, but does not depend on TRPM8 signaling in brown adipocytes or sensory neurons of the PVN.


Glucose Intolerance , TRPM Cation Channels , Animals , Male , Mice , Body Weight , Diet, High-Fat/adverse effects , Glucose Intolerance/metabolism , Mice, Knockout , Nestin/metabolism , Obesity/metabolism , TRPM Cation Channels/genetics , TRPM Cation Channels/metabolism
6.
J Laryngol Otol ; 137(8): 851-865, 2023 Aug.
Article En | MEDLINE | ID: mdl-36169002

OBJECTIVE: To assess hearing rehabilitation in patients with congenital aural atresia using an active middle-ear implant (Vibrant Soundbridge). METHODS: Of a cohort of 70 microtia and atresia patients, 10 underwent Vibrant Soundbridge implantation between 2008 and 2021. Two of the 10 patients had binaural implantation, resulting in 12 ears for analysis. Pre- and post-operative audiometry data were analysed, and patient satisfaction was evaluated. Surgical issues regarding coupling sites and outcomes were analysed. RESULTS: Pure tone average (0.5, 1, 2 and 4 kHz) improved from a pre-operative mean (standard deviation) of 65.3 (8.7) dB HL to a post-operative mean of 26.8 (4.9) dB HL. This resulted in a mean pure tone average gain of 38.5 dB HL. The results indicate no obvious difference between stapes (n = 8) and incus (n = 4) coupling. The mean effective gain for 0.5, 1, 2 and 4 kHz was -17.8 dB HL (standard deviation = 4.3). Concerning effective gain, Vibrant Soundbridge performed best at 2 kHz. Patients reported high overall satisfaction, good sound quality and strongly improved directional hearing. CONCLUSION: An active middle-ear implant (Vibrant Soundbridge) allows hearing rehabilitation in selected atretic ears, and provides long-term hearing stability in children and adults.


Ear , Ossicular Prosthesis , Adult , Child , Humans , Treatment Outcome , Ear/surgery , Ear/abnormalities , Hearing
7.
Sci Rep ; 12(1): 18194, 2022 10 28.
Article En | MEDLINE | ID: mdl-36307461

The present review systematically analyzed in vitro and in situ studies investigating physical diffusion barriers (sealants, desensitizer or adhesives) to prevent the development or the progression of root (dentin) demineralization. Three electronic databases (PubMed-Medline, CENTRAL, Ovid-EMBASE) were screened for studies from 1946 to 2022. Cross-referencing was used to identify further articles. Article selection and data abstraction were done in duplicate. Languages were not restricted. The type of outcome was not restricted, and their mean differences (MD) were calculated using fixed- or random-effects models. Risk of Bias was graded using Risk of Bias 2.0 tool. From 171 eligible studies, 34 were selected for full-text analysis evaluating 69 different materials, and 17 studies-still evaluating 36 different materials-were included (3 in situ and 14 in vitro). Ten studies evaluated desensitizers; 8 adhesives; and 1 infiltration. Meta-analyses were possible for all 17 studies. Meta-analyses revealed that lesion depth after no treatment was significantly higher than after the application of single-step adhesives (MD[95%CI] = - 49.82[- 69.34; - 30.30]) and multi-step adhesives (MD[95%CI]=-60.09 [-92.65, -27.54]). No significant differences in the lesion depth increase between single- and multi-step adhesives could be observed (MD[95%CI]=30.13 [-21.14, 81.39]). Furthermore, compared to no treatment the increase of the lesion depth was significantly hampered using desensitizers (MD[95%CI] = - 38.02[- 51.74; - 24.31]). Furthermore, the included studies presented unclear or high risk. A physical diffusion barrier can significantly hamper the increase of lesion depth under cariogenic conditions. Furthermore, multi-step adhesives seem not to be more effective than single-step adhesives. However, this conclusion is based on only few in vitro and in situ studies.


Adhesives , Dentin
8.
J Psychiatr Res ; 155: 33-41, 2022 11.
Article En | MEDLINE | ID: mdl-35987176

The neural correlates of major depressive disorder (MDD) remain disputed. In the absence of reliable biological markers, the dysfunction and interaction of neural networks have been proposed as pathophysiological neural mechanisms in depression. Here, we examined the functional connectivity (FC) of brain networks. 51 healthy volunteers (mean age 33.57 ± 7.80) and 55 individuals diagnosed with MDD (mean age 33.89 ± 11.00) participated by performing a resting-state (rs) fMRI scan. Seed to voxel FC analyses were performed. Compared to healthy control (HC), MDD patients showed higher connectivity between the hippocampus and the anterior cingulate cortex (ACC) and lower connectivity between the insula and the ACC. The MDD group displayed lower connectivity between the inferior parietal lobule (IPL) and the superior frontal gyrus (SFG). The current data replicate previous findings regarding the cortico-limbic network (hippocampus - ACC connection) and the salience network (insula - ACC connection) and provide novel insight into altered rsFC in MDD, in particular involving the hippocampus - ACC and the insula - ACC connection. Furthermore, altered connectivity between the IPL and SFG indicates that the processing in higher cognitive processes such as attention and working memory is affected in MDD. These data further support dysfunctional neuronal networks as an interesting pathophysiological marker in depression.


Depressive Disorder, Major , Adult , Brain/diagnostic imaging , Brain Mapping , Depressive Disorder, Major/diagnostic imaging , Gyrus Cinguli , Humans , Limbic System , Magnetic Resonance Imaging , Young Adult
10.
Philos Trans A Math Phys Eng Sci ; 380(2227): 20200426, 2022 Jul 11.
Article En | MEDLINE | ID: mdl-35599570

Humans are impressive social learners. Researchers of cultural evolution have studied the many biases shaping cultural transmission by selecting who we copy from and what we copy. One hypothesis is that with the advent of superhuman algorithms a hybrid type of cultural transmission, namely from algorithms to humans, may have long-lasting effects on human culture. We suggest that algorithms might show (either by learning or by design) different behaviours, biases and problem-solving abilities than their human counterparts. In turn, algorithmic-human hybrid problem solving could foster better decisions in environments where diversity in problem-solving strategies is beneficial. This study asks whether algorithms with complementary biases to humans can boost performance in a carefully controlled planning task, and whether humans further transmit algorithmic behaviours to other humans. We conducted a large behavioural study and an agent-based simulation to test the performance of transmission chains with human and algorithmic players. We show that the algorithm boosts the performance of immediately following participants but this gain is quickly lost for participants further down the chain. Our findings suggest that algorithms can improve performance, but human bias may hinder algorithmic solutions from being preserved. This article is part of the theme issue 'Emergent phenomena in complex physical and socio-technical systems: from cells to societies'.


Cultural Evolution , Social Learning , Algorithms , Humans , Learning , Problem Solving
11.
World J Surg ; 46(8): 1980-1986, 2022 08.
Article En | MEDLINE | ID: mdl-35445826

BACKGROUND AND AIM: The relationship between time to surgery and risk of postoperative complications and re-intervention has not been conclusively investigated in pediatric perforated appendicitis (PA). The aim of this study was to determine whether time to appendectomy (TTA) is a risk factor for postoperative complications and re-intervention in a cohort of children undergoing appendectomy for PA. METHODS: A total of 254 children (age: 8.7 ± 3.7 years) undergoing appendectomy for PA were retrospectively evaluated and stratified into Group I-III according to the Clavien-Dindo classification for postoperative complications (Group I n = 218, 86%; Group II n = 7, 3%; Group III n = 29, 11%). RESULTS: The TTA was comparable between all groups (group I: 8.8 ± 9.2 h; group II: 7.8 ± 5.3 h; group III: 9.5 ± 9.6 h; overall: 8.8 ± 9.1 h; p = 0.885). A C-reactive protein (CRP) value at admission of ≥128.6 mg/l indicated a higher risk for developing Grade II complications with no need for re-intervention (OR: 3.963; 95% CI: 1.810-8.678; p = 0.001) and Grade III complications with the need for re-intervention (OR: 3.346; 95% CI: 1.456-7.690; p = 0.004). This risk was independent of the TTA (OR: 1.007; 95% CI: 0.980-1.035; p = 0.613). CONCLUSIONS: Appendectomy can be delayed by an average time delay of about 9 h in children with PA without increasing the risk of postoperative complications and re-intervention, also in patients at high risk defined by the initial CRP level ≥ 128.6 mg/l. This data may support the correct risk-adjusted scheduling of surgical interventions in times of limited capacity.


Appendicitis , Appendectomy/adverse effects , Appendicitis/complications , Appendicitis/surgery , Child , Child, Preschool , Humans , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Retrospective Studies , Risk Factors
12.
Anaesthesiologie ; 71(6): 462-466, 2022 06.
Article De | MEDLINE | ID: mdl-35226122

Acute adrenal cortex insufficiency is a rare disease, which is hard to diagnose because of its diffuse symptoms. Symptoms, such as general weakness, nausea or vomiting, fatigue, hyponatremia, hyperkalemia, hypoglycemia and pronounced hypotension up to shock can be crucial in the diagnosis of an adrenal cortex crisis. The underlying disease of adrenal cortex insufficiency is also characterized by not always obvious symptoms, which are differently expressed depending on whether it is the primary or secondary type.After the diagnosis is made it is important to educate the patients, determine the optimal dosage of the substitution and ensure the compliance of the patients to optimize the further process and avoid an adrenal crisis. An adrenal crisis is one of the reasons for a higher mortality of these patients, which is well-described in the current literature. Descriptions of fatal courses and their reasons are rare; however, knowledge of the disease and the importance of rapid intervention is very important, especially for physicians who work in the emergency room or intensive care unit (ICU).This article reports about a female patient with a known secondary adrenal cortex insufficiency who developed the complete picture of an adrenal crisis. Despite rapid diagnosis and initiation of treatment massive brain damage could not be averted due to hypoxia and hypoglycemia. This case report demonstrates the potential symptoms, in particular a massive hypoglycemia and an initial shock refractory to catecholamine. It also shows the severity of that disease and the importance of rapid treatment even though it is difficult to make the diagnosis.


Adrenal Cortex , Adrenal Insufficiency , Hypoglycemia , Acute Disease , Adrenal Cortex Hormones , Adrenal Insufficiency/diagnosis , Cerebral Cortex , Diagnosis, Differential , Female , Humans , Hydrocortisone , Hypoglycemia/diagnosis , Hypoglycemic Agents , Hypoxia/complications
13.
Clin. transl. oncol. (Print) ; 24(2): 331-341, febrero 2022. ilus, graf
Article En | IBECS | ID: ibc-203438

IntroductionPenile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias.Materials and methodsA cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed.ResultsOur study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival.ConclusionPD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.


Health Sciences , Carcinoma, Squamous Cell , Tumor Microenvironment , Penile Neoplasms , Cells/immunology , Survivorship , Papillomavirus Infections
14.
Phys Rev Lett ; 128(1): 010605, 2022 Jan 07.
Article En | MEDLINE | ID: mdl-35061500

We identify an unconventional algebraic scaling phase in the quantum dynamics of long-range hopping, free fermions, which are exposed to continuous local measurements. The algebraic phase occurs for hopping decay exponents 1

15.
Clin Transl Oncol ; 24(2): 331-341, 2022 Feb.
Article En | MEDLINE | ID: mdl-34449004

INTRODUCTION: Penile carcinomas are rare tumors throughout Europe. Therefore, little attention is drawn to this disease. That makes it important to study tumor-associated key metrics and relate these to known data on penile neoplasias. MATERIALS AND METHODS: A cohort of 60 well-defined penile invasive carcinomas with known human papillomavirus (HPV) infection status was investigated. Data on tumor type, grading and staging were recorded. Additionally, data on the peri- and intratumoral immune cell infiltrate in a semiquanititave manner applying an HE stain were assessed. RESULTS: Our study showed a significant correlation of immune cell infiltrate and pT stage with overall survival. Therefore, in a subset of tumors, PD-L1 staining was applied. For tumor proportion score (TPS), 26 of 30 samples (87%) were scored >0%. For the immune cell score (IC), 28 of 30 samples (93%) were defined as >0% and for CPS, 29 of 30 samples (97%) scored >0. PD-L1 expression was not associated with overall survival. CONCLUSION: PD-L1 is expressed in penile carcinomas, providing a rationale for targeted therapy with checkpoint inhibitors. We were able to show that immune reaction appears to be prognostically relevant. These data enhance the need for further studies on the immune cell infiltrate in penile neoplasias and show that PD-L1 expression is existent in our cohort, which may be a potential target for checkpoint inhibitor therapy.


B7-H1 Antigen/analysis , Carcinoma, Squamous Cell/chemistry , Carcinoma, Squamous Cell/immunology , Carcinoma, Squamous Cell/pathology , Papillomavirus Infections/immunology , Papillomavirus Infections/pathology , Penile Neoplasms/chemistry , Penile Neoplasms/immunology , Penile Neoplasms/pathology , Tumor Microenvironment , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/virology , Cohort Studies , Humans , Male , Middle Aged , Neoplasm Invasiveness , Penile Neoplasms/virology
16.
Animal ; 15(3): 100156, 2021 Mar.
Article En | MEDLINE | ID: mdl-33573950

The ability to accurately estimate fat mass and fat-free mass (FFM) has the potential to improve the way in which sow body condition can be managed in a breeding herd. Bioelectrical impedance spectroscopy (BIS) has been evaluated as a practical technique for assessment of body composition in several livestock species, but similar work is lacking in sows. Bioelectrical impedance uses population-specific algorithms that require values for the apparent resistivities of body fluids and body proportion factors. This study comprised three major aims: (i) to derive apparent resistivity coefficients for extracellular water (ECW) and intracellular water (ICW) required for validation of BIS predictions of total body water (TBW) in live sows against standard reference tracer dilution methods; (ii) to develop predictions of TBW to body composition prediction algorithms, namely FFM, by developing a body geometry correction factor (Kb) and (iii) to compare the BIS predictions of FFM against existing impedance predictors and published prediction equations for use in sows, based on physical measurements of back-fat depth and BW (P2-based predictors). Whole body impedance measurements and the determination of TBW by deuterium dilution and ECW by bromide dilution were performed on 40 Large White x Landrace sows. Mean apparent resistivity coefficients of body fluids were 431.1 Ω.cm for ECW and 1827.8 Ω.cm for ICW. Using these coefficients, TBW and ECW were over-estimated by 6.5 and 3.3%, respectively, compared to measured reference values, although these differences were not statistically different (P > 0.05). Mean Kb was 1.09 ±â€¯0.14. Fat-free mass predictions were 194.9 kg, which equates to 60.9% of total sow weight, and 183.0 kg for BIS and the deuterium dilution method, respectively. Mean differences between the predicted and measured FFM values ranged from -8.2 to 32.7%, but were not statistically different (P > 0.05). Method validation (leave-one-out procedure) revealed that mean differences between predicted and measured values were not statistically significant (P > 0.05). Of the impedance-based predictors, equivalence testing revealed that BIS displayed the lowest test bias of 11.9 kg (8.2%), although the P2-based prediction equations exhibited the lowest bias and percentage equivalence, with narrow limits of agreement. Results indicate although differences between mean predicted and measured values were not significantly different, relatively wide limits of agreement suggest BIS as an impractical option for assessing body composition in individual sows compared to the use of existing prediction equations based on BW and back fat.


Body Composition , Body Water , Animals , Electric Impedance , Female , Indicator Dilution Techniques/veterinary , Spectrum Analysis/veterinary , Swine
17.
J Am Acad Audiol ; 32(2): 99-106, 2021 02.
Article En | MEDLINE | ID: mdl-33321539

BACKGROUND: Previous research demonstrated benefits of adaptive digital microphone technologies (ADMTs) in adults with single-sided deafness (SSD) having a cochlear implant (CI). Children with SSD are especially affected by background noise because of their noise exposure in kindergarten and school. PURPOSE: This article aims to evaluate possible effects of ADMT on speech recognition in background noise in children with SSD who use a CI. STUDY SAMPLE: Ten children between 5 and 11 years of age were included. DATA COLLECTION AND ANALYSIS: Speech recognition in noise was assessed for one frontal distant and two lateral speakers. The speech stimulus was presented at a speech level of 65 dB(A) and noise at a level of 55 dB(A). For the presentation condition with one frontal speaker, four listening conditions were assessed: (1) normal-hearing (NH) ear and CI turned off; (2) NH ear and CI; (3) NH ear and CI with ADMT; and (4) NH ear with ADMT and CI. Listening conditions (2) to (4) were also tested for each lateral speaker. The frontal speaker was positioned directly in front of the participant, whereas the lateral speakers were positioned at angles of 90 degrees and -90 degrees to the participant's head. RESULTS: Children with SSD who use a CI significantly benefit from the application of ADMT in speech recognition in noise for frontal distant and for lateral speakers. Speech recognition improved significantly with ADMT at the CI and the NH ears. CONCLUSION: Application of ADMT significantly improves speech recognition in noise in children with SSD who use a CI and can therefore be highly recommended. The decision of whether to apply ADMT at the CI NH ear or bilaterally should be made for each child individually.


Cochlear Implantation , Cochlear Implants , Speech Perception , Adult , Child , Humans , Speech , Technology
18.
Psychiatry Res ; 295: 113627, 2021 01.
Article En | MEDLINE | ID: mdl-33290945

The aim of this study was to investigate the relationships between the process of identity formation, emotion regulation (intrapersonal and interpersonal), avatar identification, and gaming in adolescents and young adults. Data (from eight standardized questionnaires) were collected from 37 non-gamers (NGs), 133 non-problematic gamers (NPGs), and 37 problematic gamers (PGs). The results showed that PGs had higher scores in lack of emotional consciousness, lack of emotional clarity, and expressive suppression, while also having lower scores in cognitive reappraisal and interpersonal emotion regulation than NPGs or NGs. They also had higher scores in ruminative exploration and lower scores in exploration in depth. In addition, factors associated with Internet gaming disorder (IGD) differed by gender. In females, lack of emotional clarity, interpersonal emotion regulation, commitment, and in-depth exploration were associated with IGD. In males, however, negative emotions, lack of emotional consciousness, lack of emotional clarity, suppressive expression, and ruminative exploration were associated with the disorder. These results highlighted the need to consider gender specificities when caring for video game-players and using of therapies or psychotherapeutic techniques to improve their emotional processes and promote their identity-construction.


Emotional Regulation/physiology , Internet Addiction Disorder/psychology , Interpersonal Relations , Social Identification , Video Games/psychology , Adolescent , Adult , Behavior, Addictive/diagnosis , Behavior, Addictive/psychology , Child , Cross-Sectional Studies , Female , Humans , Internet Addiction Disorder/diagnosis , Male , Surveys and Questionnaires , Young Adult
19.
Blood ; 136(24): 2786-2802, 2020 12 10.
Article En | MEDLINE | ID: mdl-33301031

T-cell prolymphocytic leukemia (T-PLL) is a poor-prognostic neoplasm. Differentiation stage and immune-effector functions of the underlying tumor cell are insufficiently characterized. Constitutive activation of the T-cell leukemia 1A (TCL1A) oncogene distinguishes the (pre)leukemic cell from regular postthymic T cells. We assessed activation-response patterns of the T-PLL lymphocyte and interrogated the modulatory impact by TCL1A. Immunophenotypic and gene expression profiles revealed a unique spectrum of memory-type differentiation of T-PLL with predominant central-memory stages and frequent noncanonical patterns. Virtually all T-PLL expressed a T-cell receptor (TCR) and/or CD28-coreceptor without overrepresentation of specific TCR clonotypes. The highly activated leukemic cells also revealed losses of negative-regulatory TCR coreceptors (eg, CTLA4). TCR stimulation of T-PLL cells evoked higher-than-normal cell-cycle transition and profiles of cytokine release that resembled those of normal memory T cells. More activated phenotypes and higher TCL1A correlated with inferior clinical outcomes. TCL1A was linked to the marked resistance of T-PLL to activation- and FAS-induced cell death. Enforced TCL1A enhanced phospho-activation of TCR kinases, second-messenger generation, and JAK/STAT or NFAT transcriptional responses. This reduced the input thresholds for IL-2 secretion in a sensitizer-like fashion. Mice of TCL1A-initiated protracted T-PLL development resembled such features. When equipped with epitope-defined TCRs or chimeric antigen receptors, these Lckpr-hTCL1Atg T cells gained a leukemogenic growth advantage in scenarios of receptor stimulation. Overall, we propose a model of T-PLL pathogenesis in which TCL1A enhances TCR signals and drives the accumulation of death-resistant memory-type cells that use amplified low-level stimulatory input, and whose loss of negative coregulators additionally maintains their activated state. Treatment rationales are provided by combined interception in TCR and survival signaling.


Immunologic Memory , Leukemia, Prolymphocytic, T-Cell/immunology , Proto-Oncogene Proteins/immunology , Receptors, Antigen, T-Cell/immunology , Signal Transduction/immunology , T-Lymphocytes/immunology , Animals , Humans , Leukemia, Prolymphocytic, T-Cell/genetics , Leukemia, Prolymphocytic, T-Cell/pathology , Mice , Mice, Knockout , Proto-Oncogene Proteins/genetics , Receptors, Antigen, T-Cell/genetics , Signal Transduction/genetics , T-Lymphocytes/pathology
20.
J Biomech ; 112: 110010, 2020 11 09.
Article En | MEDLINE | ID: mdl-32977296

Conventionally used textile prosthesis for traditional open surgical repair (OSR) of aortic aneurysms have a lower compliance than the native aortic tissue. Graft placements lead to an acute drop in compliance which effects cardiovascular risk and the development of graft related complications. A custom-made spring casing was applied to a Dacron graft segment under physiological pressure conditions within a five-element biventricular mock circulation loop, to investigate experimentally a concept to improve the compliance of a conventional aortic prosthesis by changing the transverse graft cross-section. Two different prosthesis locations, proximal and distal of compliant silicone tubing were used to study uniaxial graft compression with an elastic device. To characterise the devices' performance by means of pulse pressure (PP), diastolic pressure (Pdia) and pulse wave velocity(PWV), fluid pressures and flow were recorded. In a proximal graft setting (ascending aorta repair) elastic uniaxial compression with a custom-made spring casing (2 cm width) could significantly reduce PP by 10-14% (p < .001) and slowed PWV from 6.7 to 5.2 m/s (22%, p = .002). Applied to a graft in a distal position, the spring casing demonstrated less impact on PP (2-10%), but significantly reduced PWV in this mock aorta segment from 13.7 to 5.5 m/s (60%, p = .004). In conclusion, a newly conceptualised spring casing applied to the external wall of synthetic aortic grafts can reduce PP and slow PWV. By restoring elastic aortic recoil in stiff textile aortic prostheses, the presented concept is a potential solution to improve long-term aortic prosthesis related complications.


Pulse Wave Analysis , Stents , Aorta , Blood Vessel Prosthesis , Prosthesis Design
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