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Wastewater surveillance for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA has demonstrated useful correlation with both coronavirus disease 2019 (COVID-19) cases and clinical testing positivity at the community level. Wastewater surveillance on college campuses has also demonstrated promising predictive capacity for the presence and absence of COVID-19 cases. However, to date, such monitoring has most frequently relied upon composite samplers and reverse transcription quantitative PCR (RT-qPCR) techniques, which limits the accessibility and scalability of wastewater surveillance, particularly in low-resource settings. In this study, we trialed the use of tampons as passive swabs for sample collection and reverse transcription loop-mediated isothermal amplification (RT-LAMP), which does not require sophisticated thermal cycling equipment, to detect SARS-CoV-2 RNA in wastewater. Results for the workflow were available within three hours of sample collection. The RT-LAMP assay is approximately 20 times less analytically sensitive than RT-droplet digital PCR. Nonetheless, during a building-level wastewater surveillance campaign concurrent with independent weekly clinical testing of all students, the method demonstrated a three-day positive predictive value (PPV) of 75% (excluding convalescent cases) and same-day negative predictive value (NPV) of 80% for incident COVID-19 cases. These predictive values are comparable to that reported by wastewater monitoring using RT-qPCR. These observations suggest that even with lower analytical sensitivity the tampon swab and RT-LAMP workflow offers a cost-effective and rapid approach that could be leveraged for scalable building-level wastewater surveillance for COVID-19 potentially even in low-resource settings.

Significance Statement Posttranslational guanidinylation of ApoC3, a major constituent of triglyceride-rich lipoproteins, enhances ApoC3?s proinflammatory properties in uremia. Guanidinylated ApoC3 (gApoC3) is generated by guanidine and urea, and accumulates significantly in the plasma of patients with CKD, and in the kidneys of mouse models of CKD. In humanized mice, gApoC3 promotes kidney tissue fibrosis and suppresses regeneration after vascular injury. Importantly, in a large observational trial examining the clinical relevance of this posttranslational modification in patients with CKD, higher plasma gApoC3 intensity was associated with adverse renal and cardiovascular outcomes. Therefore, gApoC3 represents a novel mediator of kidney injury and CKD-associated vascular disease and offers a potential treatment target to halt progression and to prevent vascular disease in patients with CKD.Background Coexistent CKD and cardiovascular diseases are highly prevalent in Western populations and account for substantial mortality. We recently found that apolipoprotein C-3 (ApoC3), a major constituent of triglyceride-rich lipoproteins, induces sterile systemic inflammation by activating the NOD-like receptor protein-3 (NLRP3) inflammasome in human monocytes via an alternative pathway.Methods To identify posttranslational modifications of ApoC3 in patients with CKD, we used mass spectrometry to analyze ApoC3 from such patients and from healthy individuals. We determined the effects of posttranslationally modified ApoC3 on monocyte inflammatory response in vitro, as well as in humanized mice subjected to unilateral ureter ligation (a kidney fibrosis model) and in a humanized mouse model for vascular injury and regeneration. Finally, we conducted a prospective observational trial of 543 patients with CKD to explore the association of posttranslationally modified ApoC3 with renal and cardiovascular events in such patients.Results We identified significant posttranslational guanidinylation of ApoC3 (gApoC3) in patients with CKD. We also found that mechanistically, guanidine and urea induce guanidinylation of ApoC3. A 2D-proteomic analysis revealed that gApoC3 accumulated in kidneys and plasma in a CKD mouse model (mice fed an adenine-rich diet). In addition, gApoC3 augmented the proinflammatory effects of ApoC3 in monocytes in vitro. In humanized mice, gApoC3 promoted kidney tissue fibrosis and impeded vascular regeneration. In CKD patients, higher gApoC3 plasma levels (as determined by mass spectrometry) were associated with increased mortality as well as with renal and cardiovascular events.Conclusions Guanidinylation of ApoC3 represents a novel pathogenic mechanism in CKD and CKD-associated vascular injury, pointing to gApoC3 as a potential therapeutic target.

Treatment of tracheal stenosis is occasionally performed in combination with wound healing modulators to manipulate new extracellular matrix (ECM) formation and prevent fibrosis. Hyaluronic acid (HA) and collagen-polyvinylpyrrolidone (collagen-PVP) decrease fibrosis in experimental tracheal healing. However, they have not been used clinically as their effect on ECM components, which modify tracheal scarring, has not been described. Objective. To evaluate the effect of the application of HA, collagen-PVP, a mixture of HA and collagen-PVP (HA+collagen-PVP), and mitomycin C on the expression of decorin, matrix metalloproteinase 1 (MMP1), and MMP9, as well as the type of collagen and deposits formed in the scar after resection and end-to-end anastomosis (REEA) of the cervical trachea using an experimental model. Materials and Methods. Thirty dogs underwent REEA of the cervical trachea and were treated with different wound healing modulators: group I (n=6), control; group II (n=6), HA; group III (n=6), collagen-PVP; group IV (n=6), HA+collagen-PVP; and group V (n=6), mitomycin C. The dogs were evaluated clinically and endoscopically for 4 weeks. Subsequently, macroscopic and microscopic changes, expression of ECM proteins, and collagen deposition in tracheal scars were analysed. Results. Groups II, III, and IV showed reduced endoscopic, macroscopic, and microscopic inflammation, improved neovascularization, high decorin expression (p<0.01, analysis of variance (ANOVA)), and moderate expression of MMP1 (p<0.003, ANOVA) and type I and III collagen (p<0.05, Kruskal–Wallis). Groups IV and V developed fewer collagen deposits (p<0.001, ANOVA). Conclusion. Treatment with HA and collagen-PVP improved post-REEA healing by increasing neovascularization, stimulating the expression of decorin, and regulating the expression of MMP1, as well as type I and III collagen and their deposition.

Objectives Previous studies in a high-income country have demonstrated that people with and without low back pain (LBP) have an implicit bias that bending and lifting with a flexed lumbar spine is dangerous. These studies present two key limitations: use of a single group per study; people who recovered from back pain were not studied. Our aims were to evaluate: implicit biases between back posture and safety related to bending and lifting in people who are pain-free, have a history of LBP or have current LBP in a middle-income country, and to explore correlations between implicit and explicit measures within groups. Methods Exploratory cross-sectional study including 174 participants (63 pain-free, 57 with history of LBP and 54 with current LBP). Implicit biases between back posture and safety related to bending and lifting were assessed with the Implicit Association Test (IAT). Participants completed paper-based (Bending Safety Belief [BSB]) and online questionnaires (Tampa Scale of Kinesiophobia; Back Pain Attitudes Questionnaire). Results Participants displayed significant implicit bias between images of round-back bending and lifting and words representing “danger” (IATD-SCORE: Pain-free group: 0.56 (IQR=0.31–0.91; 95% CI [0.47, 0.68]); history of LBP group: 0.57 (IQR=0.34–0.84; 95% CI [0.47, 0.67]); current LBP group: 0.56 (IQR=0.24–0.80; 95% CI [0.39, 0.64])). Explicit measures revealed participants hold unhelpful beliefs about the back, perceiving round-back bending and lifting as dangerous (BSBthermometer: Pain-free group: 8 (IQR=7–10; 95% CI [7.5, 8.5]); history of LBP group: 8 (IQR=7–10; 95% CI [7.5, 9.0]); current LBP group: 8.5 (IQR=6.75–10; [7.5, 9.0])). There was no correlation between implicit and explicit measures within the groups. Conclusions In a middle-income country, people with and without LBP, and those who recovered from LBP have an implicit bias that round-back bending and lifting is dangerous.

Introduction: the diagnostic performance of [64Cu]-DOTAGA-PSMA PET–CT imaging was compared retrospectively to [18F]-PSMA PET–CT in prostate cancer patients with recurrent disease and in the primary staging of selected patients with advanced local and possible metastatic disease. Methods: We retrospectively selected a total of 100 patients, who were consecutively examined in our department, with biochemical recurrence after radical prostatectomy or who had progressive local and possible metastatic disease in the last 3 months prior to this investigation. All patients were examined with a dedicated PET–CT scanner (Biograph; Siemens Healthineers). A total of 250 MBq (3.5 MBq per kg bodyweight, range 230–290 MBq) of [64Cu]-DOTAGA-PSMA or [18-F]-PSMA was applied intravenously. PET images were performed 1 h post-injection (skull base to mid-thigh). The maximum standardized uptake values (SUVmax) of PSMA-positive lesions and the mean standardized uptake value (SUVmean) of the right liver lobe were measured. Results: All but 9/50 of the patients (18%; PSA range: 0.01–0.7 µg/L) studied with [64Cu]-DOTAGA-PSMA and 6/50 of the ones (12%; PSA range: 0.01–4.2) studied with [18F]-PSMA had at least one positive PSMA lesion shown by PET–CT. The total number of lesions was higher with [64Cu]-DOTAGA-PSMA (209 vs. 191); however, the median number of lesions was one for [64Cu]-DOTAGA-PSMA and two for [18F]-PSMA. Interestingly, the median SUVmean of the right liver lobe was slightly higher for [18F]-PSMA (11.8 vs. 8.9). Conclusions: [64Cu]-DOTAGA-PSMA and [18F]-PSMA have comparable detection rates for the assessment of residual disease in patients with recurrent or primary progressive prostate cancer. The uptake in the liver is moderately different, and therefore at least the SUVs of the lesions in both studies would not be comparable.

Background and ObjectivesCognitive impairment in multiple sclerosis (MS) is associated with functional connectivity abnormalities. While there have been calls to use functional connectivity measures as biomarkers, there remains to be a full understanding of why they are affected in MS. In this cross-sectional study, we tested the hypothesis that functional network regions may be susceptible to disease-related “wear and tear” and that this can be observable on co-occurring abnormalities on other magnetic resonance metrics. We tested whether functional connectivity abnormalities in cognitively impaired patients with MS co-occur with (1) overlapping, (2) local, or (3) distal changes in anatomic connectivity and cerebral blood flow abnormalities.MethodsMultimodal 3T MRI and assessment with the Brief Repeatable Battery of Neuropsychological tests were performed in 102 patients with relapsing-remitting MS and 27 healthy controls. Patients with MS were classified as cognitively impaired if they scored ≥1.5 SDs below the control mean on ≥2 tests (n = 55) or as cognitively preserved (n = 47). Functional connectivity was assessed with Independent Component Analysis and dual regression of resting-state fMRI images. Cerebral blood flow maps were estimated, and anatomic connectivity was assessed with anatomic connectivity mapping and fractional anisotropy of diffusion-weighted MRI. Changes in cerebral blood flow and anatomic connectivity were assessed within resting-state networks that showed functional connectivity abnormalities in cognitively impaired patients with MS.ResultsFunctional connectivity was significantly decreased in the anterior and posterior default mode networks and significantly increased in the right and left frontoparietal networks in cognitively impaired relative to cognitively preserved patients with MS (threshold-free cluster enhancement corrected at p ≤ 0.05, 2 sided). Networks showing functional abnormalities showed altered cerebral blood flow and anatomic connectivity locally and distally but not in overlapping locations.DiscussionWe provide the first evidence that functional connectivity abnormalities are accompanied by local cerebral blood flow and structural connectivity abnormalities but also demonstrate that these effects do not occur in exactly the same location. Our findings suggest a possibly shared pathologic mechanism for altered functional connectivity in brain networks in MS.

Introduction: The most widely used pharmacological treatment for Parkinson’s disease is levodopa, the precursor for dopamine formation in the brain. Over time, the effectiveness of levodopa decline...

Key points: Suppression of corticospinal excitability is reliably observed during preparation for a range of motor actions, leading to the belief that this preparatory inhibition is a physiologically obligatory component of motor preparation. The neurophysiological function of this suppression is uncertain. We restricted the time available for participants to engage in preparation and found no evidence for preparatory inhibition. The function of preparatory inhibition can be inferred from our findings that sensory stimulation can disrupt motor output in the absence of preparatory inhibition, but enhance motor output when inhibition is present. These findings suggest preparatory inhibition may be a strategic process which acts to protect prepared actions from external interference. Our findings have significant theoretical implications for preparatory processes. Findings may also have a pragmatic benefit in that acoustic stimulation could be used therapeutically to facilitate movement, but only if the action can be prepared well in advance. Abstract: Shortly before movement initiation, the corticospinal system undergoes a transient suppression. This phenomenon has been observed across a range of motor tasks, suggesting that it may be an obligatory component of movement preparation. We probed whether this was also the case when the urgency to perform a motor action was high, in a situation where little time was available to engage in preparatory processes. We controlled the urgency of an impending motor action by increasing or decreasing the foreperiod duration in an anticipatory timing task. Transcranial magnetic stimulation (TMS; experiment 1) or a loud acoustic stimulus (LAS; experiment 2) were used to examine how corticospinal and subcortical excitability were modulated during motor preparation. Preparatory inhibition of the corticospinal tract was absent when movement urgency was high, though motor actions were initiated on time. In contrast, subcortical circuits were progressively inhibited as the time to prepare increased. Interestingly, movement force and vigour were reduced by both TMS and the LAS when movement urgency was high, and enhanced when movement urgency was low. These findings indicate that preparatory inhibition may not be an obligatory component of motor preparation. The behavioural effects we observed in the absence of preparatory inhibition were induced by both TMS and the LAS, suggesting that accessory sensory stimulation may disrupt motor output when such stimulation is presented in the absence of preparatory inhibition. We conclude that preparatory inhibition may be an adaptive strategy which can serve to protect the prepared motor action from external interference.

Association studies have linked alterations of blood‐derived microRNAs (miRNAs) with colorectal cancer (CRC). Here, we performed a microarray‐based comparison of the profiles of 2549 miRNAs in 80 blood samples from healthy donors and patients with colorectal adenomas, colorectal diverticulitis and CRC at different stages. Confirmation by quantitative real‐time PCR (RT‐PCR) was complemented by validation of identified molecules in another 36 blood samples. No variations in miRNA levels were observed in samples from patients with colorectal adenomas and diverticulitis or from healthy donors. However, there were 179 CRC‐associated miRNAs of differential abundance compared to healthy controls. Only three – miR‐1225‐5p, miR‐1207‐5p and miR‐4459 – exhibited increased levels at all CRC stages. Most deregulated miRNAs (128/179, 71%) specifically predicted metastatic CRC. Pathway analysis found several cancer‐related pathways to which the miRNAs contribute in various ways. In conclusion, miRNA levels in blood vary throughout CRC progression and affect cellular functions relevant to haematogenous CRC progression and dissemination. The identified biomarker and therapeutic candidates require further confirmation of their clinical relevance., Here, we performed a comprehensive study on the abundance variations of 2549 miRNAs in blood from 80 healthy donors and patients with colorectal disease. We further validated the results in 36 independent samples by quantitative real‐time PCR. Patients with colorectal adenomas or diverticulitis and healthy donors exhibited no difference in their miRNA profiles, while patients with colorectal cancer displayed miRNAs with differential abundance in a stage‐specific manner. The miRNAs identified in our study contribute to several cancer‐related pathways relevant to colorectal cancer progression and haematogenous dissemination.

Background The extracellular matrix (ECM) is a network of proteins and glycosaminoglycans that provides structural and biochemical cues to cells. In the kidney, the ECM is critical for nephrogenesis; however, the dynamics of ECM composition and how it relates to 3D structure during development is unknown. Methods Using embryonic day 14.5 (E14.5), E18.5, postnatal day 3 (P3), and adult kidneys, we fractionated proteins based on differential solubilities, performed liquid chromatography-tandem mass spectrometry, and identified changes in ECM protein content (matrisome). Decellularized kidneys were stained for ECM proteins and imaged in 3D using confocal microscopy. Results We observed an increase in interstitial ECM that connects the stromal mesenchyme to the basement membrane (TNXB, COL6A1, COL6A2, COL6A3) between the embryo and adult, and a transient elevation of interstitial matrix proteins (COL5A2, COL12A1, COL26A1, ELN, EMID1, FBN1, LTBP4, THSD4) at perinatal time points. Basement membrane proteins critical for metanephric induction (FRAS1, FREM2) were highest in abundance in the embryo, whereas proteins necessary for integrity of the glomerular basement membrane (COL4A3, COL4A4, COL4A5, LAMB2) were more abundant in the adult. 3D visualization revealed a complex interstitial matrix that dramatically changed over development, including the perinatal formation of fibrillar structures that appear to support the medullary rays. Conclusion By correlating 3D ECM spatiotemporal organization with global protein abundance, we revealed novel changes in the interstitial matrix during kidney development. This new information regarding the ECM in developing kidneys offers the potential to inform the design of regenerative scaffolds that can guide nephrogenesis in vitro.

Amyloid light chain (AL) cardiomyopathy is the most malignant specific cardiomyopathy. According to international recommendations, it should be ruled out non‐invasively using the serum free light chain (FLC) ratio and immunofixation electrophoresis in both serum and urine. Here, we report on a 69‐year‐old female patient with new‐onset heart failure with mid‐range ejection fraction. Cardiac imaging was highly suggestive of cardiac amyloidosis. Amyloid scintigraphy showed faint myocardial tracer uptake according to Perugini Score 1, but immunofixation was negative and the FLC ratio was normal, despite a slight increase in lambda FLCs. Endomyocardial biopsy revealed advanced myocardial lambda immunoglobulin light chain deposition. Clinically relevant extracardiac amyloid organ infiltration could not be detected. Conclusively, non‐invasive testing can in rare cases fail to exclude isolated AL amyloid cardiomyopathy. We suggest that even slight increases in serum lambda or kappa FLCs should be considered abnormal in suspected cardiac amyloidosis if non‐invasive testing delivers discrepant results.

Transurethral resection of the prostate and open prostatectomy have been the standard of care for the surgical treatment of benign prostatic obstruction (BPO) over decades. New emerging techniques for the surgical management of BPO have been currently introduced, but might be associated with new, unusual complications. We herewith report on two patients with a rectal perforation after aquablation treatment of BPO. In the first case, the diagnosis was made 2 days after the aquablation procedure due to unspecific postoperative symptoms. A complex combined open/endoscopic repair of the defect was carried out thereafter. As a consequence, a rectoscopy was routinely performed since then following each aquablation procedure. In the second case, intraoperative rectoscopy after uneventful aquablation revealed the rectal perforation. The perforation was clipped immediately with an over the scope-clip by colonoscopy. These two cases of a rectal perforation after aquablation of the prostate demonstrate an unusual complication and its complex management. Diagnostic delay complicates its treatment. Therefore, immediate rectoscopy should be performed routinely after the aquablation procedure.

Background Pollen food allergy syndrome (PFAS) is a frequently underdiagnosed disease due to diverse triggers, clinical presentations, and test results. This is especially relevant in geographic areas with a broad spectrum of pollen sensitization, such as Southern Europe. Objectives To elucidate similarities and differences of PFAS in nine Southern European centers and identify associated characteristics and unique markers of PFAS. Methods As part of the @IT.2020 Multicenter Study, 815 patients with seasonal allergic rhinitis (SAR), aged 10-60 years, were recruited in seven countries. They completed questionnaires regarding SAR, comorbidities, family history, and PFAS, and underwent skin prick testing (SPT) and serum IgE testing. Results Of the 815 patients, 167 (20.5%) reported PFAS reactions. Most commonly, eliciting foods were kiwi (58, 34.7%), peach (43, 25.7%), and melon (26, 15.6%). Reported reactions were mostly local (216/319, 67.7%), occurring within 5 min of contact with elicitors (209/319, 65.5%). Associated characteristics included positive IgE to at least one panallergen (profilin, PR-10, or nsLTP) (p = 0.007), maternal PFAS (OR: 3.716, p = 0.026), and asthma (OR: 1.752, p = 0.073). Between centers, heterogeneity in prevalence (Marseille: 7.5% vs. Rome: 41.4%, p < 0.001) and of clinical characteristics was apparent. Cypress played a limited role, with only 1/22 SPT mono-sensitized patients reporting a food reaction (p < 0.073). Conclusions PFAS is a frequent comorbidity in Southern European SAR patients. Significant heterogeneity of clinical characteristics in PFAS patients among the centers was observed and may be related to the different pollen sensitization patterns in each geographic area. IgE to panallergen(s), maternal PFAS, and asthma could be PFAS-associated characteristics., EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology; Euroimmun [118583], SA was supported by the EAACI Fellowship Award of the European Academy of Allergology and Clinical Immunology. The study has been supported by an unrestricted grant from Euroimmun (grant number 118583). The ESEP assay has been provided by Euroimmun. The Informatics Platform AllergyCARD (TM) and the app AllergyMonitor (R) have been provided by TPS Production.

Background Spirituality can impact patients’ attitudes and decisions about treatment and end-of-life care when coping with cancer. Previous studies documented health-related quality of life (HRQoL) and spiritual well-being (SWB) as positively correlated within a general cancer patient population, but little is known about their association in the primary brain tumor population. We sought to measure SWB in primary brain tumor patients and evaluate whether it was associated with HRQoL. Methods Six-hundred and six patients treated at The Preston Robert Tisch Brain Tumor Center at Duke between December 16, 2013 and February 28, 2014 with data in the PRoGREss registry are included in this retrospective analysis. Each patient completed the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being 12 (FACIT-Sp-12) and -Fatigue (FACIT-F), and the Functional Assessment of Cancer Therapy-General and -Brain (FACT-G and FACT-Br). Results Mean age was 49.1 years (SD = 13.5 years), male (N = 328, 54.1%), married (N = 404, 66.7%), at least college-educated (N = 381, 62.9%), and diagnosed with a high-grade glioma (N = 412, 68.0%). Multiple regression analyses were performed on both the FACT-G and the FACT-Br using the FACIT-Sp-12 sub-scales of Meaning/Peace and Faith, FACIT-F, belief in God or a higher power, prayer, gender, tumor grade, and Karnofsky Performance Status (KPS) as predictors. We found that greater SWB (measured by FACIT-Sp-12) was associated with better HRQoL (measured by FACT-G and FACT-Br; p < .0001). Conclusion The association between reported SWB and reported improved HRQoL emphasizes the importance of spirituality in primary brain tumor patients, suggesting SWB must be considered in strategies to improve HRQoL.

Purpose: The aim of the study was to investigate the relationship between the forms of youth activity (in a virtual environment and in the real world) and their mental health in the period of forced social isolation related to the COVID-19 pandemic. The findings presented here are part of a larger international project (research-all.org). Methods: The subjects were students of primary and secondary schools in Krakow (N = 455), aged 11 to 18 (M = 15.38, SD = 2.10). The instruments used in this study were: the MHC-SF Karas, Cieciuch and Keyes wellbeing scale, the Connor-Davidson CD-RSC resilience scale, and the DASS-21 Lovibond scale designed to measure depression, anxiety and stress. The participants also reported the amount of time they spent on eight types of activity (online and offline) during and before social isolation. Results: Correlation analysis showed that the more time students spend actively in a virtual environment, the higher the level of depression (r = 0.27;p < 0.001), anxiety (r = 0.25;p < 0.001), stress (r = 0.25;p < 0.001). The duration of online activity is also negatively correlated with psychological well-being (r = -0.13;p = 0.013), emotional well-being (r = -0.15;p = 0.003) and social well-being (r = -0.12;p = 0.026). Well-being increases with a higher number of activities that are not mediated by a screen medium (r = 0.17;p = 0.001). Conclusions: Social isolation resulted in an increase in online activity both in education and in the social life of young people. The results obtained indicate the intensification of negative affectivity in adolescents who spend more time in the online environments. Moreover, the protective role of non-Internet physical and social activities for the mental health of young people has been demonstrated.

Aims After summarizing current concepts for the role of TRPC cation channels in cardiac cells and in processes triggered by mechanical stimuli arising e.g. during pressure overload, we analysed the role of TRPC1 and TRPC4 for background Ca2+ entry (BGCE) and for cardiac pressure overload induced transcriptional remodelling. Methods and results Mn2+-quench analysis in cardiomyocytes from several Trpc-deficient mice revealed that both TRPC1 and TRPC4 are required for BGCE. Electrically-evoked cell shortening of cardiomyocytes from TRPC1/C4-DKO mice was reduced, whereas parameters of cardiac contractility and relaxation assessed in vivo were unaltered. As pathological cardiac remodelling in mice depends on their genetic background, and the development of cardiac remodelling was found to be reduced in TRPC1/C4-DKO mice on a mixed genetic background, we studied TRPC1/C4-DKO mice on a C57BL6/N genetic background. Cardiac hypertrophy was reduced in those mice after chronic isoproterenol infusion (−51.4%) or after one week of transverse aortic constriction (TAC; −73.0%). This last manoeuvre was preceded by changes in the pressure overload induced transcriptional program as analysed by RNA sequencing. Genes encoding specific collagens, the Mef2 target myomaxin and the gene encoding the mechanosensitive channel Piezo2 were up-regulated after TAC in wild type but not in TRPC1/C4-DKO hearts. Conclusions Deletion of the TRPC1 and TRPC4 channel proteins protects against development of pathological cardiac hypertrophy independently of the genetic background. To determine if the TRPC1/C4-dependent changes in the pressure overload induced alterations in the transcriptional program causally contribute to cardio-protection needs to be elaborated in future studies.

Brustkrebs ist eine der haufigsten Krebserkrankungen wahrend der Schwangerschaft. Von schwangerschaftsassoziiertem Brustkrebs spricht man, wenn die Erkrankung wahrend der Schwangerschaft, im ersten postpartalen Jahr oder wahrend der Stillzeit auftritt. Diagnostik und Therapie sind insofern herausfordernd, da nicht nur das Wohl der Patientin, sondern auch das des ungeborenen Feten bedacht werden mussen. Mammographie mit abdomineller Abschirmung, Sonographie und Stanzbiopsie gelten als sichere diagnostische Mittel. Die Indikation zur operativen Therapie wird in Analogie zur nichtgraviden Patientin gestellt: Hier kommen je nach Befund sowohl brusterhaltende Therapieformen (BET) als auch ablative Verfahren in Frage. Die Strahlentherapie nach BET sollte erst nach der Entbindung erfolgen. Sowohl Antrazyklin- als auch Taxan-haltige Standardregime gelten wahrend der Schwangerschaft als relativ sicher und konnen ab dem zweiten Trimenon bis 3 Wochen prapartal eingesetzt werden. Eine HER2-zielgerichtete Therapie sowie eine endokrine Therapie sind wahrend der Schwangerschaft kontraindiziert.

Respiratory syncytial virus (RSV) commonly causes severe respiratory tract infections in infants, peaking between 2 and 6 months of age; an age at which direct vaccination is unlikely to be effective. Maternal immunization can deliver high levels of antibodies to newborns, providing immediate protection. Following natural infection, antibodies targeting the prefusion conformation of RSV F protein (PreF) have the greatest neutralizing capacity and thus, may provide infants with a high degree of RSV protection when acquired through maternal vaccination. However, the influence of anti-PreF maternal antibodies on infant immunity following RSV exposure has not been elucidated. To address this knowledge gap, offspring born to dams immunized with a RSV PreF vaccine formulation were challenged with RSV and their immune responses were analyzed over time. These studies demonstrated safety and efficacy for RSV-challenged, maternally-immunized offspring but high and waning maternal antibody levels were associated with differential innate and T cell immunity.

BackgroundCognitive behavior therapy (CBT) is effective for most patients with a social anxiety disorder (SAD) but a substantial proportion fails to remit. Experimental and clinical research suggests that enhancing CBT using imagery-based techniques could improve outcomes. It was hypothesized that imagery-enhanced CBT (IE-CBT) would be superior to verbally-based CBT (VB-CBT) on pre-registered outcomes.MethodsA randomized controlled trial of IE-CBT v. VB-CBT for social anxiety was completed in a community mental health clinic setting. Participants were randomized to IE (n = 53) or VB (n = 54) CBT, with 1-month (primary end point) and 6-month follow-up assessments. Participants completed 12, 2-hour, weekly sessions of IE-CBT or VB-CBT plus 1-month follow-up.ResultsIntention to treat analyses showed very large within-treatment effect sizes on the social interaction anxiety at all time points (ds = 2.09–2.62), with no between-treatment differences on this outcome or clinician-rated severity [1-month OR = 1.45 (0.45, 4.62), p = 0.53; 6-month OR = 1.31 (0.42, 4.08), p = 0.65], SAD remission (1-month: IE = 61.04%, VB = 55.09%, p = 0.59); 6-month: IE = 58.73%, VB = 61.89%, p = 0.77), or secondary outcomes. Three adverse events were noted (substance abuse, n = 1 in IE-CBT; temporary increase in suicide risk, n = 1 in each condition, with one being withdrawn at 1-month follow-up).ConclusionsGroup IE-CBT and VB-CBT were safe and there were no significant differences in outcomes. Both treatments were associated with very large within-group effect sizes and the majority of patients remitted following treatment.

RATIONALE AND OBJECTIVE: The use of kidney histopathology for predicting kidney failure is not established. We hypothesized that use of histopathological features of kidney biopsy specimens would improve prediction of clinical outcomes made using demographic and clinical variables alone. STUDY DESIGN: Retrospective cohort study and development of a clinical prediction model. SETTING AND PARTICIPANTS: All 2720 individuals from the Biopsy Biobank Cohort of Indiana who underwent a kidney biopsy between 2002 and 2015 and had at least two years of follow-up. NEW PREDICTORS & ESTABLISHED PREDICTORS: Demographic variables, comorbidities, baseline clinical characteristics, and histopathological features. OUTCOMES: Time to kidney failure, defined as sustained estimated glomerular filtration rate

Three inherited autosomal dominant conditions-BRCA-related hereditary breast and ovarian cancer (HBOC), Lynch syndrome (LS) and familial hypercholesterolemia (FH)-have been termed the Centers for Disease Control and Prevention Tier 1 (CDCT1) genetic conditions, for which early identification and intervention have a meaningful potential for clinical actionability and a positive impact on public health1. In typical medical practice, genetic testing for these conditions is based on personal or family history, ethnic background or other demographic characteristics2. In this study of a cohort of 26,906 participants in the Healthy Nevada Project (HNP), we first evaluated whether population screening could efficiently identify carriers of these genetic conditions and, second, we evaluated the impact of genetic risk on health outcomes for these participants. We found a 1.33% combined carrier rate for pathogenic and likely pathogenic (P/LP) genetic variants for HBOC, LS and FH. Of these carriers, 21.9% of participants had clinically relevant disease, among whom 70% had been diagnosed with relevant disease before age 65. Moreover, 90% of the risk carriers had not been previously identified, and less than 19.8% of these had documentation in their medical records of inherited genetic disease risk, including family history. In a direct follow-up survey with all carriers, only 25.2% of individuals reported a family history of relevant disease. Our experience with the HNP suggests that genetic screening in patients could identify at-risk carriers, who would not be otherwise identified in routine care.

Many college students experience the death of someone close to them and could be at risk for complicated grieving. Their primary sources of support may be unavailable as family members may live far away and their peers may be unprepared to respond to their grief. In addition, college students are exposed to a variety of stressors that could result in maladaptive coping. Furthermore, although most college-aged students use social media, little is known about its impact on grieving. The purpose of this study was to examine the degree to which social support, coping, continuing bonds, and social media use predicted complicated grief and posttraumatic growth in a sample of college students who had experienced an interpersonal loss. Participants (N = 258; 77.5% female, M age = 19.98, SD = 1.41) completed an online survey assessing the aforementioned constructs using Likert-type scales. Findings from two hierarchical regressions indicated that coping variables accounted for the greatest percentage of variance in grieving outcomes with avoidant-emotional coping being the most robust predictor of complicated grief and problem-focused coping accounting for considerable variance in posttraumatic growth (both were associated positively with the outcomes). As hypothesized, continuing bonds explained variance in both grieving outcomes with externalized continuing bonds and maintaining continuing bonds on social media predicting complicated grief and internalized continuing bonds contributing to posttraumatic growth (also all positively associated). Social support from family also was predictive of posttraumatic growth in the positive direction. Future research directions and implications for practice are discussed with the hope that this research might inform the development of interventions to assist college students who are grieving.

Primary central nervous system lymphoma (PCNSL) is a subtype of non-Hodgkin’s lymphoma that involves the brain, spinal cord, or leptomeninges, without evidence of systemic disease. This rare disease accounts for ~ 3% of all primary central nervous system (CNS) tumors. Methotrexate-based regimens are the standard of care for this disease with overall survival rates ranging from 14 to 55 months. Relapse after apparent complete remission can occur. We sought to understand the outcomes of patients who relapsed. This is an IRB-approved investigation of patients treated at our institution between 12/31/2004 and 10/12/2016. We retrospectively identified all cases of PCNSL as part of a database registry and evaluated these cases for demographic information, absence or presence of relapse, location of relapse, treatment regimens, and median relapse-free survival. This analysis identified 44 patients with a pathologically confirmed diagnosis of PCNSL. Mean age at diagnosis was 63.1 years (range 20–86, SD = 13.2 years). Of the 44 patients, 28 patients successfully completed an initial treatment regimen without recurrence or toxicity that required a change in therapy. Relapse occurred in 11 patients with the location of relapse being in the CNS only (n = 5), vitreous fluid only (n = 1), outside CNS only (n = 3), or a combination of CNS and outside of the CNS (n = 2). Sites of relapse outside of the CNS included testes (n = 1), lung (n = 1), adrenal gland (n = 1), kidney/adrenal gland (n = 1), and retroperitoneum (n = 1). Median relapse-free survival after successful completion of therapy was 6.7 years (95% CI 1.1, 12.6). After successful initial treatment, PCNSL has a propensity to relapse, and this relapse can occur both inside and outside of the CNS. Vigilant monitoring of off-treatment patients with a history of PCNSL is necessary to guide early diagnosis of relapse and to initiate aggressive treatment.

Scientific reports 12(1), 1551 (2022). doi:10.1038/s41598-022-04775-1, Intense X-ray pulses from free-electron lasers can trigger ultrafast electronic, structural and magnetic transitions in solid materials, within a material volume which can be precisely shaped through adjustment of X-ray beam parameters. This opens unique prospects for material processing with X rays. However, any fundamental and applicational studies are in need of computational tools, able to predict material response to X-ray radiation. Here we present a dedicated computational approach developed to study X-ray induced transitions in a broad range of solid materials, including those of high chemical complexity. The latter becomes possible due to the implementation of the versatile density functional tight binding code DFTB+ to follow band structure evolution in irradiated materials. The outstanding performance of the implementation is demonstrated with a comparative study of XUV induced graphitization in diamond., Published by Macmillan Publishers Limited, part of Springer Nature, [London]