Search

Background Anxious apprehension about feared body symptoms is thought to play a crucial role in the development, chronicity, and treatment of panic disorder (PD). In the present study, we therefore aim to elucidate the role of defensive reactivity to anticipated unpleasant symptoms in PD which can contribute to a better understanding of pathomechanisms of PD as well as identification of potential targets in PD-focused interventions. By measuring amygdala dependent potentiation of the startle reflex, we aimed to investigate whether ( 1 ) PD patients exhibit a specifically increased defensive reactivity to anticipated unpleasant body symptoms and ( 2 ) whether clinical severity of panic symptomatology varies with magnitude of defensive activation. Methods Defensive mobilization to anticipated threat was investigated in 73 patients with a primary diagnosis of panic disorder with agoraphobia (PDA) and 52 healthy controls (HC). Threat of symptom provocation was established by a standardized hyperventilation task and contrasted to threat-of-shock to the forearm of the participant. Results Patients with PDA and HC did not differ in their defensive responses during anticipation of shock. In contrast, patients with severe PDA as compared to HC exhibited increased defensive response mobilization and reported more anxiety and panic symptoms during anticipation of feared body symptoms. Moreover, startle potentiation during anticipation of hyperventilation covaried with the severity of panic symptomatology. Conclusions The present findings suggest that increased defensive mobilization during anticipation of body symptoms is a neurobiological correlate of severe PDA which should be specifically targeted in PD interventions and might be used to monitor treatment success.

The molecular understanding of the pathophysiological changes elicited by diabetes in platelets may help in further elucidating the involvement of this pseudo-cell in the increased risk of developing cardiovascular disease and thrombosis in diabetic subjects. We aimed to investigate the differential characteristics of platelets from diabetic patients and nondiabetic controls to unveil the molecular mechanisms behind the increased platelet reactivity in diabetes. We compared platelets from diabetic and control subjects by 2 dimensional-electrophoresis followed by mass spectrometry. Changes in selected differential proteins were validated by immunoprecipitation assays and western blot. Platelet aggregation was measured by light transmittance aggregometry induced by collagen and ADP, and dynamic coagulation analysis of whole blood was measured by thromboelastometry. We observed significant differences in proteins related to platelet aggregation, cell migration, and cell homeostasis. Subjects with diabetes showed higher platelet aggregation and thrombogenicity and higher contents of the stress-related protein complex HSPA8/Hsp90/CSK2α than nondiabetic subjects. Changes in the chaperones HSPA8 and Hsp90, and in CSK2α protein contents correlated with changes in platelet aggregation and blood coagulation activity. In conclusion, the complex HSPA8/Hsp90/CSK2α is involved in diabetes-related platelet hyperreactivity. The role of the HSPA8/Hsp90/CSK2α complex may become a molecular target for the development of future preventive and therapeutic strategies for platelet dysfunction associated with diabetes and its complications.

Background and aims Glycoproteins play a key role in inflammatory and cardiometabolic processes. Their implication in atherosclerosis in type 1 diabetes (T1D) is unknown. We assessed the relationships between classic inflammatory markers, glycoproteins measured by nuclear magnetic resonance (1H-NMR), and preclinical atherosclerosis in these patients. Methods and results We selected patients with T1D, without cardiovascular disease (CVD), with: age ≥40 years, nephropathy (micro/macroalbuminuria), or ≥10 years of evolution with another risk factor. The presence of plaque (intima-media thickness >1.5 mm) was determined by ultrasonography. Concentrations of high-sensitive C-reactive protein (hsCRP), circulating leukocytes (classical inflammation markers) and 1H-NMR-glycoproteins (GlycA, GlycB, GlycF, and the height/width [H/W] ratios of GlycA and GlycB) were determined. We included 189 patients (58% male, age 47.0 [40.7–55.2] years). Thirty-five percent presented plaques (22%, ≥2 plaques). There was no association between hsCRP or leukocytes and atherosclerosis. However, in age- and sex-adjusted models, GlycA, GlycF, and the H/W ratios of GlycA and GlycB gradually increased with the number of plaques (0, 1, ≥2 plaques) only in patients without statins (p Conclusion In T1D individuals without lipid-lowering treatment, 1H-NMR-glycoproteins were independently associated with the presence and amount of carotid atherosclerosis, unlike other classical inflammatory markers. Further studies are needed to ascertain their utility as CVD biomarkers.

Metal–organic framework (MOF) thin films represent a milestone in the development of future technological breakthroughs. The processability of MOFs as films on surfaces together with their major features (i.e. tunable porosity, large internal surface area, and high crystallinity) is broadening their range of applications to areas such as gas sensing, microelectronics, photovoltaics, and membrane-based separation technologies. Despite the recent attention that MOF thin films have received, many challenges still need to be addressed for their manufacturing and integrability, especially when an industrial scale-up perspective is envisioned. In this brief review, we introduce several appealing approaches that have been developed in the last few years. First, a summary of liquid phase strategies that comprise microfluidic methods and supersaturation-driven crystallization processes is described. Then, gas phase approaches based on atomic layer deposition (ALD) are also presented. ISSN:2051-6347 ISSN:2051-6355

Clonal heterogeneity in multisited or recurrent lymphoid neoplasms is a phenomenon that has been increasingly studied in recent years. However, in mucosa-associated lymphoid tissue (MALT) lymphomas it remains largely unexplored. Patients diagnosed at our institution with multisited MALT lymphoma, from January 2009 to October 2018, were studied. Molecular studies were performed for the detection of clonally rearranged immunoglobulin by polymerase chain reaction.In all, 91 patients were included. Of those, 28 had a multisited disease and in 16 clonality studies were done. In eight cases, multifocal involvement was synchronous and in eight metachronous. Patients with non-gastric gastrointestinal tract involvement tended to disseminate within the same tract, without observing other specific dissemination patterns. Four cases (25%) had clonal heterogeneity at the different organs involved. All patients with late relapses (two patients) had different clones. The majority of patients with multisited MALT lymphomas presented with the same clone in the different involved organs, identifying a different clone in those with late relapses. These patients could represent de novo neoplasms, rather than a relapse. This could mean that some individuals might have a genetic predisposition to develop this type of lymphoma and it could also have clinical implications regarding therapeutic decisions.

Purpose of Review The increasing number of contributions in the field of small-scale robotics is significantly associated with the progress in material science and process engineering during the last half century. With the objective of integrating the most optimal materials for the propulsion of these motile micro- and nanosystems, several manufacturing strategies have been adopted or specifically developed. This brief review covers some recent advances in materials and fabrication of small-scale robots with a focus on the materials serving as components for their motion and actuation. Recent Findings Integration of a wealth of materials is now possible in several micro- and nanorobotic designs owing to the advances in micro- and nanofabrication and chemical synthesis. Regarding light-driven swimmers, novel photocatalytic materials and deformable liquid crystal elastomers have been recently reported. Acoustic swimmers are also gaining attention, with several prominent examples of acoustic bubble-based 3D swimmers being recently reported. Magnetic micro- and nanorobots are increasingly investigated for their prospective use in biomedical applications. The adoption of different materials and novel fabrication strategies based on 3D printing, template-assisted electrodeposition, or electrospinning is briefly discussed. Summary A brief review on fabrication and powering of small-scale robotics is presented. First, a concise introduction to the world of small-scale robotics and their propulsion by means of magnetic fields, ultrasound, and light is provided. Recent examples of materials and fabrication methodologies for the realization of these devices follow thereafter., Current Robotics Reports, 2 (4), Topical Collection on Nanorobotics and Microrobotics

Background: Although cardiovascular disease (CVD) remains the leading cause of mortality in type 1 diabetes (T1D), the use of cardioprotective drugs is scarce. We aimed to evaluate the impact of carotid ultrasonography (US) on the improvement in cardiovascular risk factors (CVRFs) in T1D.Methods: T1D patients without CVD meeting criteria for lipid treatment according to guidelines (age ≥40 years, nephropathy and/or ≥10 years of diabetes duration with ≥1 additional CVRFs) were included. The carotid-US group (US-G) underwent a standardized US protocol and CVRF assessment; recommendations were made according to subclinical atherosclerosis status. The control group (CG) followed usual clinical practice. Changes in CVRFs, specially statin use and LDL-cholesterol levels, at one year were analysed.Results: A total of 318 patients were included (51.3% female, mean age of 49.1 years and 25.5 years of diabetes duration): 211 in the US-G and 107 in the CG. Participants in the US-G had a higher baseline LDL-cholesterol than controls (114 vs. 102 mg/dL; pConclusions: Carotid-US is independently associated with an intensification of lipid-lowering therapy in a high-risk T1D population.

Targeted drug delivery from untethered microrobots is a topic of major interest in current biomedical research. The possibility to load smart materials able to administer active principles on remotely in vivo guidable microdevices constitutes one of the most attractive opportunities to overcome the drawbacks of classical untargeted delivery methodologies. Hydrogels, in particular, are ideal candidates as drug-carrying materials due to their biocompatibility, low cost, and ease of manufacturing. On the other hand, these polymers suffer from poor control over release rate and overall released amount. Starting from these premises, the present article demonstrates the possibility to tune the release of hydrogels applied on magnetically steerable microrobots by fabricating microsystems via layer-by-layer self-assembly. By doing this, the diffusion of chemicals from the hydrogel layers to the external environment can be optimized and the phenomenon of burst release can be strongly limited. The microrobotic platforms employed to transport the hydrogel active material are fabricated by employing 3D printing in combination with wet metallization and present a gold layer on their surface to enhance biocompatibility. The maneuverability of microdevices coated with both thin and thick multilayers is investigated, individuating optimized parameters for efficient actuation., Frontiers in Bioengineering and Biotechnology, 9, ISSN:2296-4185

The “innovation ecosystem” is an umbrella term used to account for the common efforts of different stakeholders to achieve innovation. Suppliers provide key parts and technologies that are complemented by products and services provided by a variety of other actors, while customers establish demand and capabilities. In this process of joint value creation, companies gain a competitive advantage by appreciating the overall value of the products and services delivered to customers. Themes including the cooperation between actors, the creation and acquisition of value by organizations, and ecosystem leadership have received increasing interest from both practitioners and scholars. Nevertheless, many knowledge gaps remain and there is urgent need to increase our understanding regarding the formation of innovation ecosystems. Although the genesis of innovation ecosystems has received limited attention to date, it has significant impact not only for research and practice, but also for policies aiming to promote the economic welfare of sectors, regions, and countries. It is crucial to understand the process of innovation ecosystem formation, because this period of ecosystem evolution is the most fragile. Therefore, external provision of the necessary conditions, resources, and activities during this period will have the highest impact. We are conducting a systematic review to understand the origins of innovation ecosystems, as well as the evolution, gaps, and trends associated with this process. Following PRISMA guidelines, we are searching the ISI Web of Science from database inception to Sept 1, 2021, for relevant studies. No restrictions on language or study design have been applied. Risk of bias, data extraction, and sensitivity analysis are being performed by two independent investigators. This talk presents the results from this work in an effort to increase our understanding regarding the formation of innovation ecosystems.

Electrical stimulation has shown great promise in biomedical applications, such as regenerative medicine, neuromodulation, and cancer treatment. Yet, the use of electrical end effectors such as electrodes requires connectors and batteries, which dramatically hamper the translation of electrical stimulation technologies in several scenarios. Piezoelectric nanomaterials can overcome the limitations of current electrical stimulation procedures as they can be wirelessly activated by external energy sources such as ultrasound. Wireless electrical stimulation mediated by piezoelectric nanoarchitectures constitutes an innovative paradigm enabling the induction of electrical cues within the body in a localized, wireless, and minimally invasive fashion. In this review, we highlight the fundamental mechanisms of acoustically mediated piezoelectric stimulation and its applications in the biomedical area. Yet, the adoption of this technology in a clinical practice is in its infancy, as several open issues, such as piezoelectric properties measurement, control of the ultrasound dosein vitro, modeling and measurement of the piezo effects, knowledge on the triggered bioeffects, therapy targeting, biocompatibility studies, and control of the ultrasound dose deliveredin vivo, must be addressed. This article explores the current open challenges in piezoelectric stimulation and proposes strategies that may guide future research efforts in this field toward the translation of this technology to the clinical scene.

Purpose Although preeclampsia (PE) is a well-established cardiovascular risk factor (CVRF) in the general population, its role in type 1 diabetes (T1D) has been scarcely studied. We assessed the association between PE and preclinical atherosclerosis in T1D. Methods We recruited 112 women without cardiovascular disease and last pregnancy ≥5 years before: (1) T1D and previous PE (T1D+/PE+; n = 28); (2) T1D without preeclampsia (T1D+/PE–; n = 28); (3) previous PE without T1D (T1D–/PE+; n = 28); and (4) controls (without T1D or PE; T1D–/PE–; n = 28). Groups were matched by age, several CVRFs, and diabetes duration and retinopathy (in T1D participants). Carotid intima-media thickness (IMT) and the presence of plaque (IMT ≥ 1.5 mm) were assessed by standardized ultrasonography protocol. Results Mean age of the participants was 44.9 ± 7.8 years (14.3% hypertension and 21.4% active smokers). Groups including T1D (T1D+/PE+ and T1D+/PE–) more frequently presented hypertension and statin treatment (23.2% vs 5.4% and 37.5% vs 8.9%; respectively; P < 0.01), without differences in other CVRFs. Carotid plaques were observed in 20.5%. In multivariate models adjusted for age, CVRF, and statins, both T1D and PE showed a similar impact on the presence of plaque, with odds ratios (95% confidence interval), 5.45 (1.36–21.9) and 4.24 (1.04–17.3), respectively. Both entities showed an additive effect when combined, both in common carotid-IMT (T1D+/PE– or T1D–/PE+, β = 0.198; T1D+/PE+, β = 0.297) and in the presence of plaque (8.53 [1.07–68.2] and 28.1 [2.67–296.4], respectively). Conclusions Previous PE was independently associated with preclinical atherosclerosis in T1D. Further studies are needed to ascertain its usefulness for stratifying risk in T1D women.

Background Primary cardiac tumors are extremely rare; most are myxomas with a benign prognosis. However, primary sarcomas are highly aggressive and treatment options are limited. Radical surgery is often not feasible and conventional therapies provide only modest results. Due to the rare nature of primary cardiac tumors, there are no proper randomized studies to guide treatment. Their complexity requires alternative approaches in order to improve treatment efficacy. Methods We isolated DNA from 5 primary cardiac sarcomas; the quality of DNA from 3 of them was sufficient to perform high-resolution single nucleotide polymorphism (SNP) array analysis. Results In the present study, molecular karyotyping revealed numerous segmental chromosomal alterations and amplifications affecting actionable genes that may be involved in disease initiation and/or progression. These include chromosomal break flanking AKT2 in undifferentiated pleomorphic rhabdomyosarcoma, chromosomal break in promoter of TERT, and gain of CDK4 and amplification of MDM2 in inflammatory myofibroblastic tumor. We detected segmental break flanking MOS in high-grade myxofibrosarcoma. In addition, the high number of chromosomal aberrations in high-grade myxofibrosarcoma may cause multiple tumor-specific epitopes, supporting the study of immunotherapy treatment in this type of aggressive tumor. Conclusion Our results provide a genetic rationale that supports an alternative, personalized therapeutic management of primary cardiac sarcomas.

Background Findings on associations of androgens and sex hormone-binding globulin (SHBG) with anxiety and depressive disorders in the general population remain inconclusive. Methods We used data of n = 993 men and n = 980 women from the Study of Health in Pomerania (SHIP, a prospective-longitudinal general population study from northeastern Germany). Immunoassay-measured serum concentrations of total testosterone, androstenedione and SHBG were assessed when participants were aged 20–80. 12-month, lifetime and incident DSM-IV anxiety and depressive disorders were assessed with the DIA-X/M-CIDI at 10-year follow-up, when participants were aged 29–89. Logistic regressions were adjusted for age, smoking, alcohol consumption, physical activity, waist circumference, hypertension and oral contraceptive use (women only) at baseline and follow-up interval. Results In men and women, androgens and SHBG were not associated significantly with incident anxiety and depressive disorders. In men, higher total testosterone predicted any 12-month (OR = 1.46) and lifetime (OR = 1.34) anxiety disorder, lifetime social phobia (OR = 2.15), and 12-month (OR = 1.48) and lifetime (OR = 1.39) specific phobia, but neither 12-month nor lifetime depression. Moreover, androstenedione in men interacted with age in predicting lifetime anxiety disorders (OR = 0.98): Higher androstenedione more strongly predicted lifetime anxiety in younger vs. older men. These findings, however, did not survive correction for multiple testing. In women, androgens and SHBG were not associated significantly with 12-month and lifetime anxiety and depressive disorders. Limitations The follow-up period was relatively long and other factors might have affected the examined associations. Conclusions Higher serum total testosterone in men and androstenedione in younger men may relate to an increased risk of anxiety disorders.

Preclinical studies point to a pivotal role of the orexin 1 (OX1) receptor in arousal and fear learning and therefore suggest the HCRTR1 gene as a prime candidate in panic disorder (PD) with/without agoraphobia (AG), PD/AG treatment response, and PD/AG-related intermediate phenotypes. Here, a multilevel approach was applied to test the non-synonymous HCRTR1 C/T Ile408Val gene variant (rs2271933) for association with PD/AG in two independent case-control samples (total n = 613 cases, 1839 healthy subjects), as an outcome predictor of a six-weeks exposure-based cognitive behavioral therapy (CBT) in PD/AG patients (n = 189), as well as with respect to agoraphobic cognitions (ACQ) (n = 483 patients, n = 2382 healthy subjects), fMRI alerting network activation in healthy subjects (n = 94), and a behavioral avoidance task in PD/AG pre- and post-CBT (n = 271). The HCRTR1 rs2271933 T allele was associated with PD/AG in both samples independently, and in their meta-analysis (p = 4.2 × 10−7), particularly in the female subsample (p = 9.8 × 10−9). T allele carriers displayed a significantly poorer CBT outcome (e.g., Hamilton anxiety rating scale: p = 7.5 × 10−4). The T allele count was linked to higher ACQ sores in PD/AG and healthy subjects, decreased inferior frontal gyrus and increased locus coeruleus activation in the alerting network. Finally, the T allele count was associated with increased pre-CBT exposure avoidance and autonomic arousal as well as decreased post-CBT improvement. In sum, the present results provide converging evidence for an involvement of HCRTR1 gene variation in the etiology of PD/AG and PD/AG-related traits as well as treatment response to CBT, supporting future therapeutic approaches targeting the orexin-related arousal system.

Cancer of unknown primary is defined as a heterogeneous group of tumours that present with metastasis, and in which attempts to identify the original site have failed. They differ from other primary tumours in their biological features and how they spread, which means they can be considered a separate entity. There are several hypotheses regarding their origin, but the most plausible explanation for their aggressiveness and chemoresistance seems to involve chromosomal instability. Depending on the type of study done, cancer of unknown primary can account for 2-9% of all cancer patients, mostly 60-75 years old. This article reviews the main clinical, pathological and molecular studies conducted to analyse and determine the origin of cancer of unknown primary. The main strategies for patient management and treatment, by both clinicians and pathologists, are also addressed.

The present work describes for the first time the production of artificial bacterial flagella (ABFs) by combining laser direct writing and wet metallization. ABFs are helical shaped microrobots that can be remotely actuated using low-strength rotating magnetic fields. They can precisely navigate liquid environments, potentially allowing in-vivo cell and drug delivery or localized microsurgery. ABFs are printed via two photon lithography (2PL) and metallized via electroless deposition. The latter is optimized to yield a nanometric CoNiP layer without damaging the delicate structures. The swimming behavior of the CoNiP coated ABFs is then studied by actuating them inside an array of electromagnetic coils.

Whether the extent of weight loss (WL) modulates bariatric surgery (BS) cardiovascular benefits has scarcely been assessed. Several WL thresholds have been commonly used to classify BS patients as good or poor responders without a proven clinical relevance. We examined the relationship between the magnitude of WL after BS and post-surgery major adverse cardiovascular-event (MACE) incidence. We also compared the performance of three different insufficient weight-loss (IWL) criteria for their association with MACE.All individuals who underwent a primary Roux-en Y gastric bypass (RYGB) or sleeve gastrectomy (SG) in our institution at least six years before data analysis (12/2020) were included in the study. Data on MACE were available in 1638 of 1700 participants (96.4%). Proportional-hazard Cox analyses were performed to ascertain the association between MACE, WL, and the three IWL criteria. IWL was defined as:50% excess weight loss (50% EWL),20% total body-weight loss (20% TBWL), and -1 standard deviation of alterable weight-loss percentage (1 SD% AWL).During a mean follow-up of 10.2 ± 2.8 years, 86 participants experienced a first post-surgery MACE. Higher WL at one year (HR: 0.77 (95% CI: 0.61-0.98)) and 5 years (HR: 0.63 (95% CI: 0.42-0.92)) was related to a lower incidence of MACE. All short-term criteria for defining IWL were similarly associated with MACE, yet1 SD% AWL identified more at-risk subjects. Five-year TBWL 20% and 5-year1 SD-AWL% were significantly associated with a higher risk for CV events. TBWL 20% identified more subjects at risk.The extent of WL is closely related to long-term MACE incidence. Patients who lost -1SD% AWL at one year or20% TBWL at five years may be considered poor responders.

AIM To compare the efficacy of the treatment with transcutaneous perineal electrostimulation versus intracavitary electrostimulation to reduce the frequency of urinary incontinence after radical prostatectomy and the impact on the quality of life (QoL). METHODS This single-blind equivalence-randomized controlled trial equally (1:1) randomly allocated men with urinary incontinence post radical prostatectomy into surface electrodes perineal group (intervention group, IG) and intra-anal probe group (control group, CG). Outcomes included changes in the 24h-Pad Test (main variable), and ICIQ-SF (International Consultation on Incontinence Questionnaire Short-Form), SF-12 (Short Form Health Survey), and I-QOL (incontinence quality of life questionnaire) questionnaires. Clinical data were collected at baseline, 6 and 10 weeks. For the comparisons between variables, χ2 test and Student's t test were used. Equivalence was analyzed by estimating the mean change (90% confidence interval) of urinary incontinence based on the Pad Test. The analysis was performed for the per-protocol and the intention-to-treat populations. Statistical significance level was set at p

Evaluate the weight trajectories after pancreas transplantation (PT) and their relationships with pancreas graft outcomes in type 1 diabetes (T1D).Retrospective cohort study. T1D individuals who underwent PT were recruited (T1D-PT; n = 194) and divided into three groups according to transplantation date: 1999-2004 (n = 57), 2005-2009 (n = 79), 2010-2015 (n = 58). For weight comparisons, a random sample of T1D without renal impairment was also recruited during 2015 (n = 61; T1D-control).The median follow-up for the T1D-PT group was 11.1 years. Despite significant weight loss at 6 months (65.7 ± 12.4 vs. 64.1 ± 11.4 Kg; p 0.001), a stepped increase was seen thereafter (60 months: 68.0 ± 14.0 Kg; p 0.001). Participants from the 2010-2015 period showed higher weight gain (p 0.001), outweighing that observed in the T1D-control (60 months: +4.69 ± 8.49 vs. -0.97 ± 4.59 Kg; p = 0.003). Weight gain between 6 and 36 months was directly associated with fasting glucose and HbA1c at 36 months, and with HbA1c at 60 months (p 0.05). However, in Cox-regression models adjusted for age, sex, and several recipient and PT-related variables, the third tertile of weight gain between 6 and 36 months showed a non-significant increase in the graft failure/dysfunction (HR 2.33 [0.75-7.27]).Weight gain post-PT was associated with glucose-related biochemical markers of graft dysfunction, which needs confirmation in further studies.

The deterioration of gait can be used as a biomarker for ageing and neurological diseases. Continuous gait monitoring and analysis are essential for early deficit detection and personalized rehabilitation. The use of mobile and wearable inertial sensor systems for gait monitoring and analysis have been well explored with promising results in the literature. However, most of these studies focus on technologies for the assessment of gait characteristics, few of them have considered the data acquisition bandwidth of the sensing system. Inadequate sampling frequency will sacrifice signal fidelity, thus leading to an inaccurate estimation especially for spatial gait parameters. In this work, we developed an inertial sensor based in-shoe gait analysis system for real-time gait monitoring and investigated the optimal sampling frequency to capture all the information on walking patterns. An exploratory validation study was performed using an optical motion capture system on four healthy adult subjects, where each person underwent five walking sessions, giving a total of 20 sessions. Percentage mean absolute errors (MAE%) obtained in stride time, stride length, stride velocity, and cadence while walking were 1.19%, 1.68%, 2.08%, and 1.23%, respectively. In addition, an eigenanalysis based graphical descriptor from raw gait cycle signals was proposed as a new gait metric that can be quantified by principal component analysis to differentiate gait patterns, which has great potential to be used as a powerful analytical tool for gait disorder diagnostics., Sensors, 21 (8), ISSN:1424-8220

Cardiovascular disease is the major cause of death in patients with type 1 diabetes. Of the available risk predictors for this population, the Steno Type 1 Risk Engine (STENO T1) is the only one that includes kidney function as a risk factor, which is a well-described independent risk factor for cardiovascular disease.We explore how simultaneous pancreas-kidney transplantation (SPKT) modifies the predicted cardiovascular risk by the STENO T1 through a retrospective study including recipients of a first SPKT between 2000 and 2016.Two hundred sixty-eight SPKT recipients with a mean age of 40 y old and a median follow-up of 10 y were included. Before transplantation, the expected incidence of cardiovascular events (CVEs) at 5 and 10 y according to STENO T1 would have been 31% and 50%, respectively, contrasting with an actual incidence of 9.3% and 16% for the same timepoints, respectively (P0.05). These differences were attenuated when STENO T1 was recalculated assuming 12th-mo glomerular filtration rate (at 5 and 10 y predicted CVE incidence was 10.5% and 19.4%, respectively). Early pancreas graft failure (hazard ratio [HR] 3.00, 95% confidence interval [CI], 1.14-7.88; P = 0.02) was an independent risk factor for post-SPKT CVE, alongside kidney graft failure (HR 2.90, 95% CI, 1.53-5.48; P = 0.001), and diabetes duration (HR 1.04, 95% CI, 1.00-1.09, P = 0.04).SPKT decreases in more than two-thirds of the predicted cardiovascular risk by the STENO T1. A functioning pancreas graft further reduces CVE risk, independently of kidney graft function.

Approximately 75% of patients with carpal tunnel syndrome (CTS) are diagnosed as idiopathic. Despite this, the presence of an underlying cause such as an anatomical variant or a systemic disease must always be suspected, especially in cases of bilateral presentation without an obvious cause, recurrence or complications. The anatomical variant known as the bifid median nerve (BMN) is a very rare abnormality that can occasionally lead to CTS. On the other hands, transthyretin-associated amyloidosis (ATTR) is one of the possible causes of bilateral CTS. We report a case where these two very rare pathologies converge as the cause of bilateral CTS and a review of the literature. We report a 71-year-old male with prior history of lumbar canal stenosis, bilateral trigger finger, rupture of the supraspinatus muscle tendon and of the long portion of the right biceps brachial. He also had 8-year-old bilateral CTS that recurred after CTS surgery. He was surgically re-intervened and was diagnosed incidentally with BMN and an ultrasound of the other hands also showed BMN. Because of all the prior musculoskeletal history, a biopsy of the transverse carpal ligament was taken showing ATTR deposits that led to the diagnosis of cardiac ATTR wild type. This case highlights the natural history of the multiple musculoskeletal manifestations related to ATTR and the importance of performing intraoperative biopsies in patients with CTS surgery as this can lead to early diagnosis of cardiac ATTR.

Background Radical prostatectomy is the gold standard treatment for men with localized prostate cancer. This technique is associated with post-operative urinary incontinence. Pelvic floor physiotherapy is a conservative, painless and economical treatment for this specific situation. Kegel exercises and perineal electrostimulation are common techniques to train pelvic floor muscles. The perineal electrostimulation can be applied to the patient with surface electrodes or by an intra-cavitary anal probe. This study proposes that transcutaneous perineal electrostimulation is as effective as intra-cavitary electrostimulation in reducing urinary incontinence secondary to radical prostatectomy. The main objective is to compare the efficacy of the treatment with transcutaneous perineal electrostimulation versus the same intra-cavitary treatment to reduce the magnitude of urinary incontinence after radical prostatectomy, and the impact on the quality of life. Methods This single-blind equivalence randomized controlled trial will include 70 man who suffer urinary incontinence post radical prostatectomy. Participants will be randomized into surface electrodes group and intra-anal probe group. The groups will receive treatment for 10 consecutive weeks. Outcomes include changes in the 24-h Pad Test, and ICIQ-SF, SF-12 and I-QoL questionnaires. Clinical data will be collected at baseline, 6 and 10 weeks after the first session, and 6 months after the end of treatment. Discussion The results will allow us to prescribe the most beneficial perineal electrostimulation technique in the treatment of urinary incontinence derived from radical prostatectomy. Trial registration ClinicalTrials.gov Identifier: NCT03587402. 27/06/2018

Last two decades has seen a growth of the research on untethered mobile small-scale robots. These motile devices display the ability to travel through fluids by transforming the energy generated by an external power source into mechanical motion. As a result, these devices are being recognized as promising platforms to break through the drawbacks of nanoparticle drug delivery systems. Among the family of small-scale devices, magnetic micro- and nanorobots, which refer to those devices wirelessly controlled by external magnetic fields, are arguably the most appealing systems for biomedical applications. Magnetic fields display biocompatibility characteristics in a wide range of conditions, and they can penetrate body tissues with minimal interaction. Additionally, magnetic fields can be generated in several forms (rotating, oscillating, gradients), enabling a rich collection of motion mechanisms, including several that mimic those of cells and microorganisms. In the present talk, we will introduce magnetic small-scale robots, their actuation principles, designs and constituent materials. Next, we will discuss about existing and potential applications in the biomedical area. Finally, we will conclude with remaining challenges for their translation into clinical applications, with a special focus in the area of intravascular drug delivery., Public Health Toxicology, 1 (S), ISSN:2732-8929

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense. Trial Registration Number: ISRCTN80046034. German Federal Ministry of Education and Research Universität Greifswald (1032)

Panic disorder (PD) has a lifetime prevalence of 2–4% and heritability estimates of 40%. The contributory genetic variants remain largely unknown, with few and inconsistent loci having been reported. The present report describes the largest genome-wide association study (GWAS) of PD to date comprising genome-wide genotype data of 2248 clinically well-characterized PD patients and 7992 ethnically matched controls. The samples originated from four European countries (Denmark, Estonia, Germany, and Sweden). Standard GWAS quality control procedures were conducted on each individual dataset, and imputation was performed using the 1000 Genomes Project reference panel. A meta-analysis was then performed using the Ricopili pipeline. No genome-wide significant locus was identified. Leave-one-out analyses generated highly significant polygenic risk scores (PRS) (explained variance of up to 2.6%). Linkage disequilibrium (LD) score regression analysis of the GWAS data showed that the estimated heritability for PD was 28.0–34.2%. After correction for multiple testing, a significant genetic correlation was found between PD and major depressive disorder, depressive symptoms, and neuroticism. A total of 255 single-nucleotide polymorphisms (SNPs) with p < 1 × 10−4 were followed up in an independent sample of 2408 PD patients and 228,470 controls from Denmark, Iceland and the Netherlands. In the combined analysis, SNP rs144783209 showed the strongest association with PD (pcomb = 3.10 × 10−7). Sign tests revealed a significant enrichment of SNPs with a discovery p-value of

Bodily disturbances, like dyspnea, elicit responses to regain homeostasis and ensure survival. However, this life-saving function can become hyperreactive, which may lead to the emergence of psychopathology. This study investigated whether maximal voluntary breath-holding time (mvBHT), a biobehavioral marker that characterizes sensitivity to respiratory stimulation, predicts defensive mobilization to cues signaling the proximity of a mild electric shock vs. a respiratory threat (shortness of breath elicited by forced breath-holding) and the opportunity to avoid threat delivery in 60 healthy participants. While the startle reflex, a measure of defensive mobilization, generally increased with the proximity of an inevitable threat, shorter breath-holding time was specifically associated with greater startle potentiation when anticipating a respiratory threat but not an electric shock. In contrast, when both threats were avoidable, the startle reflex was comparably inhibited, irrespective of mvBHT. This study suggests that mvBHT specifically predicts hypersensitive responding to an anticipated inevitable respiratory threat.

Evaluate the role of plasma metabolomics in atherosclerosis according to the presence of type 1 diabetes (T1D) or previous preeclampsia.We recruited 105 women without cardiovascular disease and last pregnancy ≥5 years previously, divided according to the presence of T1D or previous preeclampsia. Preclinical atherosclerosis was defined as the presence of carotid plaque (intima-media thickness ≥1.5 mm) assessed by ultrasonography. Metabolomics were evaluated by nuclear magnetic resonance (NMR). Bivariate and multivariate-adjusted differences in NMR-metabolomics were evaluated.The participants were 44.9 ± 8.1 years-old; 20% harbored plaques. There were significant differences in lipidic-, energetic- and nitrogen-related metabolites according to the presence of T1D/preeclampsia (p 0.05). In multivariate-adjusted models (by age, statins, blood pressure and T1D/preeclampsia), only lipidomic-related metabolites were associated with atherosclerosis in the whole sample. However, stronger associations were observed in women with previous preeclampsia (vs. without; per 0.5 mmol/L increments); phosphatidylcholine, OR 4.08 (1.32-27.22); free cholesterol, 5.18 (1.22-21.97); saturated fatty acids, OR 2.99 (1.37-6.48); w-7, OR 2.29 (1.15-4.56); and w-9 fatty acids, OR 1.49 (1.00-2.23).NMR-metabolomics showed a differential pattern according to the presence of T1D/preeclampsia in relation to preclinical atherosclerosis. Since most of these metabolites mirror lifestyle factors, they could help tailor dietetic advice in high-risk women.

BACKGROUND AND AIMS Tools to detect type 1 diabetes (T1D) individuals at overt cardiovascular disease (CVD) risk are scarce. We aimed to assess the usefulness of the score 'Steno Type 1 Risk Engine' (Steno-Risk) to identify T1D patients with advanced carotid atherosclerosis. MATERIAL AND METHODS T1D patients without CVD with at least one of the following were included: ≥40 years, diabetic nephropathy, or diabetes duration ≥10 years with ≥1 CVD risk factor. Intima-media thickness (IMT) and plaque presence (IMT ≥1.5 mm) were assessed by standardized B-mode ultrasonography. Steno-Risk was used to estimate 10-year risk (

We report for the first time on a novel Atomic Force Microscopy (AFM) technique with dual actuation capabilities using both piezo and magnetic bead actuation for advanced single-molecule force spectroscopy experiments. The experiments are performed by manipulating functionalized magnetic microbeads using an electromagnet against a stationary AFM cantilever. Magnetic actuation has been demonstrated for AFM before to actuate cantilevers, but here we report for the first time a method where we keep the cantilever stationary and accomplish actuation via free-manipulated microstructures. This method leads to a significant reduction of mechanical drift in the system since the experiments are performed without a need for a hard surface and the measured force between the cantilever and the bead is inherently differential. In addition, shrinking the size of the actuator can minimize hydrodynamic forces affecting the AFM cantilever. We conducted single-molecule force spectroscopy and force-clamp experiments with biotin/streptavidin as a model system using the new method. The new method reported herein allows applying constant force on the beads to perform force-clamp experiments without any active feedback, which might be crucial for a deeper understanding of interaction between biomolecules.

Background: Alterations in circulating amino acids, polyamines and acylcarnitines have been reported in patients with endogenous chronic hypercortisolism. However, lipid metabolites profiling and its interplay with the serum metabolome and degree of hypercortisolism in patients with active Cushing syndrome (CS) has not been previously assessed. Objective: To identify new metabolomic biomarkers associated with active CS. Methodology: Multiple UHPLC-MS platforms were used to analyze the metabolome of serum samples obtained from 25 patients with active endogenous CS and 25 controls subjects matched by propensity score (sex, BMI, T2D, DLP, HBP). Results: Metabolome of CS patients was deeply disrupted with 122 (27%) of the assessed metabolites significantly altered (p adj. 2-fold decrease). From the altered metabolites, 3 amino acids (AA), 2 acylcarnitines (ACs), 2 ceramides (CER) and 5 glycerophospholipids showed direction of effect independently associated with 24-h urinary free cortisol (MS) levels. A highly discriminant (AUC 96%) metabolome signature (n=59) characterized by lower levels of AA, ACs, polyunsaturated fatty acids (PUFA) and monoglycerophosphocolines (MGPC) together with increased levels of triacyclglycerols (TG), CER, diacylglycerophosphocholines (DGPC) and cholesteryl esters was identified and cross-validated (R2Y= 0.92, Q2Y= 0.68) using PLS-DA VIP scores >1.5. PUFA omega-6, and alanine, aspartate and glutamate metabolism resulted the most impacted canonical pathways (q-stat 19.7, 10.8 (p Conclusion: Active Cushing syndrome leads to a global proatherogenic shift in the circulating ceramides, glycerophospholipids and sphingolipids metabolites which are independently associated to the levels of urinary free cortisol being potential biomarkers of patients’ cardiovascular risk.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation—DNA methyltransferases (DNMTs)—has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.

Altres ajuts: This study was supported by [...], and the CIBERNED program (Program 1, Alzheimer Disease to Alberto Lleó and SIGNAL study, www.signalstudy.es); and partly jointly funded by Fondo Europeo de Desarrollo Regional, Unión Europea, Una manera de hacer Europa. This work was also supported by the National Institutes of Health (NIA grants 1R01AG056850 - 01A1; R21AG056974, and R01AG061566 to Juan Fortea), Fundació La Marató de TV3 (20141210 to Juan Fortea, 044412 to Amanda Jiménez and Rafael Blesa). This work was also supported by [...] and a grant from the Fundació Bancaria La Caixa to Rafael Blesa. The work of Adriana Pané is supported by the " Ajut a la Recerca Josep Font" (Hospital Clinic de Barcelona). Data collection and sharing for this project was funded by the Alzheimer's Disease Neuroimaging Initiative (ADNI) (National Institutes of Health Grant U01 AG024904) and DOD ADNI (Department of Defense award number W81XWH-12-2-0012). [...]. The Canadian Institutes of Health Research is providing funds to support ADNI clinical sites in Canada. Private sector contributions are facilitated by the Foundation for the National Institutes of Health (www.fnih.org). Midlife obesity is a risk factor for dementia. We investigated the impact of obesity on brain structure, metabolism, and cerebrospinal fluid (CSF) core Alzheimer's disease (AD) biomarkers in healthy elderly. We selected controls from ADNI2 with CSF AD biomarkers and/or fluorodeoxyglucose positron emission tomography (FDG-PET) and 3T-MRI. We measured cortical thickness, FDG uptake, and CSF amyloid beta (Aβ)1-42, p-tau, and t-tau levels. We performed regression analyses between these biomarkers and body mass index (BMI). We included 201 individuals (mean age 73.5 years, mean BMI 27.4 kg/m 2). Higher BMI was related to less cortical thickness and higher metabolism in brain areas typically not involved in AD (family-wise error [FWE]

During the last two decades, engineering motion with small-scale matter has received much attention in several areas of research, ranging from supramolecular chemistry and colloidal science to robotics and automation. The numerous discoveries and innovative concepts realized in motile micro- and nanostructures have converged in the field of small-scale swimmers. These man-made micro- and nanomachines can move in fluids by transforming different forms of energy to mechanical motion. Recently, metal–organic frameworks (MOFs), which are crystalline coordination polymers with high porosity, have been proposed as key building blocks in several small-scale swimmer designs. These materials possess the required features for motile micro- and nanodevices, such as high cargo-loading capacity, biodegradability, biocompatibility, and stimuli-responsiveness. In this review, we take a journey through the major breakthroughs and milestones realized in the area of MOF-based small-scale swimmers. First, a brief introduction to the field of small-scale swimmers is provided. Next, we review different strategies that have been reported for imparting motion to MOFs. Finally, we emphasize the incorporation of molecular machines into the MOF’s architecture as the means to create highly integrated small-scale swimmers. The strategies and developments explored in this review pave the way toward the use of motile MOFs for a variety of applications in the fields of biomedicine, environmental remediation, and on-the-fly chemistry., Chemical Reviews, 120 (20), ISSN:0009-2665, ISSN:1520-6890

Background It remains unresolved whether childhood adversities interact with genetic variation in regulator of G-protein signaling 2 (RGS2) rs4606 in predicting various anxiety and depressive disorders and whether diagnostic specificity exists in these interactions. Methods The genotype of RGS2 rs4606 was determined for N = 2,263 adults with European ancestry from the Study of Health in Pomerania. Lifetime anxiety and depressive disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fourth edition, were assessed with the Munich Composite International Diagnostic Interview (DIA-X/M-CIDI). Childhood adversities were assessed with the Childhood Trauma Questionnaire (CTQ, when participants were aged 29-89). Results Logistic regressions adjusted for sex and age revealed that rs4606 interacted with total childhood adversity in predicting each diagnostic outcome except for panic disorder and generalized anxiety disorder, uncorrected and corrected for multiple testing (odds ratio [OR] = 1.06-1.16). That is, carriers of the GG (vs. CC/CG) genotype were at decreased risk for anxiety and/or depression in the presence of low, but at increased risk in the presence of high total childhood adversity. Respective gene-environment (G × E) interactions were found for (a) comorbid anxiety and depressive disorders (OR = 1.13), but neither pure anxiety nor pure depressive disorders and (b) pure/temporally primary anxiety disorders (OR = 1.07), but not pure/temporally primary depressive disorders. The G × E interaction remained associated with depressive disorders after introducing pure/temporally primary anxiety disorders as additional predictor (OR = 1.09). Conclusions rs4606 alters the risk of developing a range of anxiety but also depressive disorders after childhood adversities. A complex risk pattern of genotype, environmental factors, and preexisting anxiety contributes to subsequent depression development.

Few epidemiological studies presented 12-month and lifetime prevalence estimates for DSM-IV mental disorders in the adult general population by sex and age up to very old age. From 2007 to 2010, DSM-IV mental disorders were assessed with the DIA-X/M-CIDI among N = 2400 participants (aged 29-89 years) from the Study of Health in Pomerania, an epidemiological study based on a two-stage stratified cluster sample randomly drawn from the adult general population in northeastern Germany. 36.3% of the sample was affected by any 12-month and 54.8% by any lifetime mental disorder. The most frequent diagnostic groups were anxiety (12-month: 14.8%, lifetime: 23.4%), substance use (12-month: 14.5%, lifetime: 25.0%), somatoform (12-month: 12.9%, lifetime: 20.4%) and depressive (12-month: 7.3%, lifetime: 18.6%) disorders. Except for substance use (higher prevalence in men) and bipolar disorders (comparable prevalence in men and women), higher 12-month and lifetime prevalence estimates were found in women vs. men. Moreover, lower 12-month and lifetime prevalence estimates were found in older (aged 60-74 or 75-89 years) vs. younger (aged 29-44 or 45-59 years) age groups. 22.6% (men: 21.1%, women: 23.9%) of those affected by any 12-month disorder met criteria for two and 13.6% (men: 9.6%, women: 16.9%) for three or more 12-month diagnoses. Similarly, 26.4% (men: 25.7%, women: 26.9%) of those affected by any lifetime disorder met criteria for two and 22.7% (men: 19.6%, women: 25.2%) for three or more lifetime diagnoses. Our findings demonstrate the frequency of mental disorders in northeastern Germany and emphasize the need for continued prevention and intervention efforts.

Background Excessive fear and anxiety are core features of anxiety disorders. Defensive response mobilization varies dynamically with threat proximity. Methods We analyzed defensive responses in 48 healthy students to an approaching external, predator-like threat (an electric shock resembling a predator attack) versus an approaching threat from inside the body (feeling of dyspnea as evoked by forced breath-holding). Threats either were inevitable or could be avoided by button press. Results Autonomic changes (heart rate, skin conductance), defensive reflex priming (startle eyeblink response), respiratory responses, and event-related potentials were assessed. Regardless of its source, when an approaching threat was inevitable, a defensive pattern emerged characterized by an increase in skin conductance, a potentiation of the startle reflex, and bradycardia. Minute ventilation increased only with approaching dyspnea. In preparation for active avoidance of either threat, startle magnitudes were inhibited and probe-elicited P3 wave amplitudes were reduced. Moreover, generation of avoidant action resulted in heart rate acceleration. Conclusions This study demonstrates common and specific defensive activation patterns for approaching external and respiratory threats. The specific modulation in respiration in response to an inevitable respiratory threat may have important implications for our understanding of the etiology of anxiety disorders, especially panic disorder.

This short article describes the origins and successes of a COST Action initiative, e-MINDS, the bringing together of two quite disparate fields, electrodeposition, and corrosion protection...

Variable Stiffness Catheter In article number 2101290 by Quentin Boehler, Bradley J. Nelson, and co‐workers, a magnetically controlled catheter that is able to continuously change its stiffness is presented. Soft, magnetic tools that are enhanced with the capability to apply and control forces during surgical intervention can significantly improve outcome of the procedure. The capabilities are demonstrated by performing a fully robotic surgery for a challenging ophthalmic intervention. Image designed by Adrián Bago González. [Image: see text]

Applied Materials Today, 9, ISSN:2352-9407

Objective To determine whether fear can be triggered when experiencing interoceptive sensations locally proximal to the primary pain region. Two groups of adolescents (11-18 years) with chronic headache ( n = 20) or chronic abdominal pain (CAP; n = 20) completed three muscle tensing tasks to induce proximal versus distal sensations: (1) "frown" task (proximal for chronic headache; distal for CAP), (2) "tighten stomach" task (proximal for CAP; distal for chronic headache), and (3) safe comparison task (clench fist). Fear and avoidance were assessed via self-report. Adolescents with CAP reported greater fear and avoidance after the proximal compared with the distal task, while adolescents with chronic headache did not. Both groups reported similar levels of fear and avoidance in the frown and safe comparison task. Results suggest that the perception of proximal interoceptive sensations appears to activate the fear system in adolescents with CAP. Future research is warranted.

To evaluate the changes in cardiovascular risk factors (CVRFs) and cardiovascular disease (CVD) in patients with type 1 diabetes (T1D) and end-stage renal disease (ESRD) who were candidates for kidney-pancreas transplantation (KPTx) from 1999 to 2017.Patients with T1D referred for KPTx evaluation were included. The cohort was divided into five groups according to the year of evaluation (1999-2002, 2003-2006, 2007-2010, 2011-2014 and 2015-2017). The control of CVRFs and the prevalence of prior CVD were evaluated.We evaluated 360 patients (64.4% men, age 38.9 ± 7.1 years). LDL-cholesterol100 mg/dl increased from 22.7% to 76.9% (1999-2002 vs. 2015-2017; p 0.001), as did the use of statins (from 24.7% to 74.5%; p 0.001). Systolic blood pressure decreased from 138.8 ± 27.6 to 125.1 ± 27.9 mmHg (p = 0.001) and current smokers from 48% to 25% (p = 0.018). Intensive insulin treatment increased from 34.4% to 93.6% (p 0.001). Diabetes duration before the initiation of renal replacement therapy increased from 23 ± 5.5 to 26.9 ± 8.9 years (p = 0.001). Overall, 30.3% had previous CVD, without significant changes over time (p = 0.699), albeit patients were older and had longer diabetes duration.Patients with T1D and ESRD referred for KPTx have better control of CVRFs over time, which might lead to a decrease in cardiovascular events.

The gene coding for glycine receptor β subunits (GLRB) has been found to be related to panic disorder and agoraphobia (PD/AG) and to be associated with altered insular BOLD activation during fear conditioning, as an intermediate phenotype of defensive system reactivity in healthy subjects. In a multicenter clinical trial on PD/AG patients we investigated in three sub-samples whether GLRB allelic variation (A/G; A-allele identified as «risk») in the single nucleotide polymorphism rs7688285 was associated with autonomic (behavioral avoidance test BAT; n = 267 patients) and neural (differential fear conditioning; n = 49 patients, n = 38 controls) measures, and furthermore with responding towards exposure-based cognitive behavioral therapy (CBT, n = 184 patients). An interaction of genotype with current PD/AG diagnosis (PD/AG vs. controls; fMRI data only) and their modification after CBT was tested as well. Exploratory fMRI results prior to CBT, revealed A-allele carriers irrespective of diagnostic status to show overall higher BOLD activation in the hippocampus, motor cortex (MC) and insula. Differential activation in the MC, anterior cingulate cortex (ACC) and insula was found in the interaction genotype X diagnosis. Differential activation in ACC and hippocampus was present in differential fear learning. ACC activation was modified after treatment, while no overall rs7688285 dependent effect on clinical outcomes was found. On the behavioral level, A-allele carriers showed pronounced fear reactivity prior to CBT which partially normalized afterwards. In sum, rs7688285 variation interacts in a complex manner with PD/AG on a functional systems level and might be involved in the development of PD/AG but not in their treatment.

Aim Although insulin resistance (IR) is a growing trait among type 1 diabetes (T1D) population, its relationship with atherosclerosis has been scarcely studied. We assessed the association between IR indexes and carotid atherosclerosis in T1D, a population at high cardiovascular disease (CVD) risk. Materials and methods We evaluated 191 participants with T1D and no prior CVD with at least one of the following criteria: ≥40 years old; diabetic nephropathy; or T1D duration ≥10 years harbouring ≥1 additional CVD risk factor. IR was assessed with the metabolic syndrome (MetS) harmonized definition proposed in 2009 and the estimated glucose disposal rate (eGDR), a T1D-specific IR surrogate marker (lower values indicating higher IR). Standardized carotid ultrasonography was performed, recording intima-media thickness (IMT), plaque presence and maximum height of plaque. Comparisons between patients according to their MetS status as well as concerning eGDR values were performed. Results The participants' median age was 47.4 (41.1-53.3) years and diabetes duration 25.7 (21.6-32.5) years. Plaque prevalence was higher in patients with greater IR (49.1%, 29.1% and 20%, P = .001, for any plaque according to decreasing eGDR tertiles). Conversely, no statistically significant higher plaque prevalence was found in participants with MetS. In multivariate analyses (adjusted for general- and T1D-specific risk factors, and statin treatment), MetS was associated with neither IMT nor plaque. On the contrary, eGDR was independently related to ≥2 plaques (P = .018) and maximum plaque height (P Conclusions In T1D, IR assessed through eGDR but not by MetS definition was independently associated with plaque burden, a predictor of CVD.

Objectives To clarify the impact of histological grades in follicular lymphoma. Methods We retrospectively analysed 250 patients diagnosed with FL treated with chemoimmunotherapy: 188 patients were grades 1-2 and 62 grade 3A. Results In our series, grade 3A FL patients were older, higher proportion of localised disease and lower bone marrow infiltration at diagnosis comparing grades 1-2 FL patients. Estimated six-year progression-free survival and time to progression showed no differences between both groups [grade 3A: 56% (95%CI: 39%-73%) and 51% (95%CI: 41%-61%) vs grades 1-2:55% (95%CI: 46%-63%) and 57% (95%CI: 49%-65%), P = .782 and P = .521, respectively]. Estimated six-year overall survival was lower, 76% (95%CI: 64%-88%) for the grade 3A group than grades 1-2 83% (95%CI: 77%-89%); P = .044. In addition to that, cumulative incidence curves of death not related to lymphoma at 10 years between groups were as follows: [0.26 (95%CI: 0.25-0.27) and 0.05 (95%CI: 0.04-0.06) for G3AFL and G1-2FL, respectively], P = .010. Grade 3A FL showed in PFS curve no relapses after 6 years. These results were absolutely reproduced in 199 patients receiving R-CHOP regimen as induction. Conclusions Our results indicate similar long-term outcomes in terms of progression-free survival and time to progression in grades 1-2 and 3A. No relapses were observed in G3AFL group after 6 years.