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To assess the association between psychotropic medications and sleep microstructure in large community-based cohorts of older people.We analyzed overnight polysomnograms of 381 women from the Study of Osteoporotic Fractures (SOF) and 2,657 men from the Osteoporotic Fractures in Men Sleep Study (MrOS), who either used no psychotropic medication (n=2,819), only benzodiazepines (n=112), or only selective serotonin reuptake inhibitors (SSRI) (n=107). Sleep microstructure (cyclic alternating pattern, CAP) was compared between the no medication group and psychotropic medication groups using the Mann-Whitney U-test. Significant differences were investigated using multivariable linear regression adjusted for confounders.CAP rate, arousal index, apnea-hypopnea index, and the frequency of slow, low-amplitude electroencephalography activation phases were significantly lower in MrOS participants using benzodiazepines than participants not taking psychotropic medication. SSRI users in MrOS experienced no altered sleep microstructure compared to those with no psychotropic use. SOF participants using benzodiazepines did not show similar associations with sleep microstructure. However, SSRI users from SOF had a significantly higher frequency of rapid, high-amplitude electroencephalography activation phases (A2 + 3) and periodic limb-movement index than participants not taking psychotropic medication. Multivariable linear regression adjusted for demographic, lifestyle, mood disorders, and health variables indicated additional significant associations between CAP rate and A2 + 3 index, respectively, and benzodiazepine usage in older men, and between CAP rate and SSRI usage in older women.We identified significant associations between sleep microstructure and psychotropic drugs in MrOS and SOF highlighting the importance of comprehensive sleep analysis, including CAP. Our results may help to better understand the differences in sleep-wake mechanisms based on psychotropic usage.Registry: ClinicalTrials.gov; Title: Outcomes of Sleep Disorders in Older Men; Identifier: NCT00070681; URL: https://clinicaltrials.gov/ct2/show/record/NCT00070681.

Background: Sleep is fragmented by brief arousals, and excessive arousal burden has been linked to increased cardiovascular (CV) risk, but mechanisms are poorly understood. Research Question: Do arousals trigger cardiac ventricular repolarization lability that may predispose people to long-term cardiovascular mortality? Study Design and Methods: This study analyzed 407,541 arousals in the overnight polysomnograms of 2,558 older men in the Osteoporotic Fractures in Men sleep study. QT and RR intervals were measured beat-to-beat starting 15 s prior to arousal onset until 15 s past onset. Ventricular repolarization lability was quantified by using the QT variability index (QTVi). Results: During 10.1 ± 2.5 years of follow-up, 1,000 men died of any cause, including 348 CV deaths. During arousals, QT and RR variability increased on average by 5 and 55 ms, respectively, resulting in a paradoxical transient decrease in QTVi from 0.07 ± 1.68 to –1.00 ± 1.68. Multivariable Cox proportional hazards analysis adjusted for age, BMI, cardiovascular and respiratory risk factors, sleep-disordered breathing and arousal, diabetes, and Parkinson disease indicated that excessive QTVi during arousal was independently associated with all-cause and CV mortality (all-cause hazard ratio, 1.20 [95% CI, 1.04-1.38; P = .012]; CV hazard ratio, 1.29 [95% CI, 1.01 -1.65; P = .043]). Interpretation: Arousals affect ventricular repolarization. A disproportionate increase in QT variability during arousal is associated with an increased all-cause and CV mortality and may reflect ventricular repolarization maladaptation to the arousal stimulus. Whether arousal-related QTVi can be used for more tailored risk stratification warrants further study, including evaluating whether arousal suppression attenuates ventricular repolarization lability and reduces subsequent mortality. Clinical Trial Registration: ClinicalTrials.gov; No.: NCT00070681; URL: www.clinicaltrials.gov

Purpose To examine the acute effects of concurrent muscle power and sport-specific endurance exercises order on immunological stress responses, muscular-fitness, and rating-of-perceived-exertion (RPE) in highly trained youth male judo athletes. Methods Twenty male participants randomly performed two concurrent training (CT) sessions; power-endurance and endurance-power. Measures of immune response (e.g., white blood cells), muscular-fitness (i.e., counter-movement-jump [CMJ]), RPE, blood-lactate, and -glucose were taken at different time-point (i.e., pre, mid, post, and post6h). Results There were significant time*order interactions for white blood cells, lymphocytes, granulocytes, granulocyte-lymphocyte-ratio, and systemic-inflammation-index. Power-endurance resulted in significantly larger pre-to-post increases in white blood cells and lymphocytes while endurance-power resulted in significantly larger pre-to-post increases in the granulocyte-lymphocyte-ratio and systemic-inflammation-index. Likewise, significantly larger pre-to-post6h white blood cells and granulocytes increases were observed following power-endurance compared to endurance-power. Moreover, there was a significant time*order interaction for blood-glucose and -lactate. Following endurance-power, blood-lactate and -glucose increased from pre-to-mid but not from pre-to-post. Meanwhile, in power-endurance blood-lactate and -glucose increased from pre-to-post but not from pre-to-mid. A significant time*order interaction was observed for CMJ-force with larger pre-to-post decreases in endurance-power compared to power-endurance. Further, CMJ-power showed larger pre-to-mid performance decreases following power-endurance, compared to endurance-power. Regarding RPE, significant time*order interactions were noted with larger pre-to-mid values following endurance-power and larger pre-to-post values following power-endurance. Conclusion CT induced acute and delayed order-dependent immune cell count alterations in highly trained youth male judo athletes. In general, power-endurance induced higher acute and delayed immunological stress responses compared to endurance-power. CMJ-force and RPE fluctuated during both CT sessions but went back to baseline 6 h post-exercise.

Animals need to cope with abundant sensory information, and one strategy is to selectively direct attention to only the most relevant part of the environment. Although the cortical networks of selective attention have been studied extensively, its underlying neurotransmitter systems, especially the role of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), remain less well understood. Increased GABAA receptor activity because of administration of benzodiazepines such as lorazepam is known to slow reactions in cognitive tasks. However, there is limited knowledge about GABAergic involvement in selective attention. Particularly, it is unknown whether increased GABAA receptor activity slows the build-up of selectivity or generally widens attentional focus. To address this question, participants (n = 29) received 1 mg lorazepam and placebo (within-subjects, double-blind) and performed an extended version of the flanker task. The spatial distribution of selective attention was studied by systematically manipulating number and position of incongruent flankers; the temporal build-up was characterized using delta plots. An online task version was presented to an independent, unmedicated sample (n = 25) to verify task effects. Under placebo and in the unmedicated sample, only the number of incongruent flankers, but not their position, influenced RTs. Incongruent flankers impaired RTs more strongly under lorazepam than placebo, especially when adjacent to the target. Delta plot analyses of RT showed that this effect persisted even when participants reacted slowly, indicating that lorazepam-induced impairments in selective attention do not result from simply slowed down build-up of selectivity. Instead, our data indicate that increased GABAA receptor activity widens the attentional focus.

Contains fulltext : 283519.pdf (Publisher’s version ) (Open Access) BACKGROUND: The assessment of symptom-rhythm correlation (SRC) in patients with persistent atrial fibrillation (AF) is challenging. Therefore, we performed a novel mobile app-based approach to assess SRC in persistent AF. METHODS: Consecutive persistent AF patients planned for electrical cardioversion (ECV) used a mobile app to record a 60-s photoplethysmogram (PPG) and report symptoms once daily and in case of symptoms for four weeks prior and three weeks after ECV. Within each patient, SRC was quantified by the SRC-index defined as the sum of symptomatic AF recordings and asymptomatic non-AF recordings divided by the sum of all recordings. RESULTS: Of 88 patients (33% women, age 68 ± 9 years) included, 78% reported any symptoms during recordings. The overall SRC-index was 0.61 (0.44-0.79). The study population was divided into SRC-index tertiles: low (

Perinatal hypoxia is one of the more common complications of the early adaptation period. This condition is defined as a disorder of tissue oxygenation during labour and is responsible for approximately 23% of neonatal mortality. Perinatal hypoxia can cause injury and failure of many organs, including the brain, heart and kidneys, mainly in the mechanism of the ischaemic-reperfusion injury. Currently, biochemical markers are more frequently incorporated in neonatal diagnostics. Routinely used in adult patients, these organ-specific chemicals enable diagnosis with high sensitivity and specificity. The manuscript presents a review of research on the use of cardiac markers (N-terminal fragment of pro-B-type natriuretic peptide, cardiac troponins I and T, and cardiac creatine kinase isoenzyme) in selected neonatal diseases. Still, no cutoff values have been established for any of the markers described in this paper. Therefore, for routine use of cardiac markers in the neonatal population, further studies are needed to determine the range of cutoff values and factors that may cause their fluctuation.

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Background. The treatment options for patients with multiple myeloma who refractory to previous bortezomib and lenalidomide therapy are limited. Pomalidomide is ап immunomodulatory agent that was registered for the treatment of patients with double refractory multiple myeloma.Aim. To evaluate efficacy, safety and optimal course of the therapy with pomalidomide in routine practice in patients with double refractory multiple myeloma.Materials and methods. Overall, 71 patients with double refractory multiple myeloma were included in the retrospective analysis. There were 36 males and 35 females. The median age was 61 years (range 35-79). According to Durie-Salmon staging system, there were 53 (79.1 %) patients in stage III, 13 (19.4 %) - stage II, and 1 (1.5 %) - stage I.The stage was unknown in 4 patients. Kidney impairment at the onset was in 10 (15 %) patients, the normal function was in 57 (85 %) patients and 4 patients had no data. Most patients (n = 68, 95.8 %) received pomalidomide in one therapy line, in 3 (4.2 %) patients - drug was given in two lines, totally 74 episodes of use. Median number of drugs prescribed prior to pomalidomide were 4 (2-9) drugs, including target ones - 2 (2-5). In the first remission 31 (43.6 %) patients received high-dose therapy with autologous stem cell transplantation. pomalidomide was administered in combination with low doses of dexamethasone (PomDex, n = 44; 59.4 %) and as a part of triple regimens (n = 30; 40.6 %). previously exposed (n = 22; 73.3 %) and new drugs (n = 8; 26.7 %) were used in the combination treatment. In 44 (61.9 %) patients pomalidomide was administered more than 3 years after the onset of the disease, median 63.5 (37-184) months. In 27 (38.1 %) patients it was given within less than 3 years after the onset, median 21 (6-36) months. The primary endpoint was progression-free survival. Secondary endpoints - pomalidomide tolerability, response rate and optimal third drug in the triple regimen. The dependence of progression-free survival, frequency of response and adverse events from the pretreatment, the choice of the third drug, gender, age, immunochemical variant, stage according to the International Staging System and to Durie-Salmon classification was studied.Results. The median time from the diagnosis to the start of pomalidomide therapy was 44.5 (6-184) months. The median of cycles with pomalidomide was 3 (1-30). The response was achieved in 52 (70 %) patients. The median progression-free survival was 4 (1-30) months, overall survival - 6 (0.5-42) months. Adverse effects were noted in 34 (46.5 %) patients. The most frequent adverse events were neutropenia grade III-IV (n = 14; 41.3 %), infection (n = 7; 20.7 %) and fatigue with limitation of daily activity (n = 6; 20.6 %). The rate of adverse events was higher in patients with triplets than doublets regimens of therapy: 43.3 % (n = 13) and 27.2 % (n = 12) respectively (p = 0.008). There were no statistically significant differences in progression-free survival between pomalidomide treatment options (two- or three-component regimen).Conclusion. Compared to the three-component therapy consisting of drugs to which refractoriness was previously diagnosed the PomDex scheme is less toxic and equally effective. Therapy with pomalidomide is effective in the majority of patients with double refractory multiple myeloma even in heavily pretreated. The toxicity is acceptable.

The present article reviews the state of the art of machine learning algorithms for the detection, prediction, and management of atrial fibrillation (AF), as well as of the development and evaluation of artificial intelligence (AI) in cardiology and beyond. Today, AI detects AF with a high accuracy using 12-lead or single-lead electrocardiograms or photoplethysmography. The prediction of paroxysmal or future AF currently operates at a level of precision that is too low for clinical use. Further studies are needed to determine whether patient selection for interventions may be possible with machine learning.In diesem Beitrag wird der aktuelle Stand von Algorithmen des maschinellen Lernens zur Erkennung, Vorhersage und Behandlung von Vorhofflimmern zusammengefasst, zudem werden die Entwicklung und Prüfung von künstlicher Intelligenz in der Kardiologie und anderen Bereichen dargelegt. Nach heutigem Stand lässt sich Vorhofflimmern mithilfe künstlicher Intelligenz in 12-Kanal- oder 1‑Kanal-Elektrokardiogrammen bzw. in Photoplethysmogrammen zuverlässig erkennen. Die Vorhersage von paroxysmalem oder neu auftretendem Vorhofflimmern hat die für den klinischen Einsatz erforderliche Genauigkeit noch nicht erreicht. Weitere Studien sind notwendig, um zu untersuchen, ob auf Basis des maschinellen Lernens eine Patientenselektion für Interventionen möglich ist.

The recent discovery of Hepatitis D (HDV)-likeviruses across a wide range of taxa led to the establishment of theKolmioviridaefamily. Recent studies suggest that kolmiovirids can be satellites of viruses other than Hepatitis B virus (HBV), challenging the strict HBV/HDV-association dogma. Studying whether kolmiovirids are able to replicate in any animal cell they enter is essential to assess their zoonotic potential. Here, we compared replication of three kolmiovirids: HDV, rodent (RDeV) and snake deltavirus (SDeV)in vitroandin vivo. We show that SDeV has the narrowest and RDeV the broadest host cell range. High resolution imaging of infected cells revealed nuclear viral hubs with a peculiar RNA-protein organization. Finally,in vivohydrodynamic delivery of infectious clones showed that both HDV and RDeV, but not SDeV, efficiently replicate in mouse liver, forming massive nuclear viral hubs. Our comparative analysis lays the foundation for the discovery of specific host factors controllingKolmioviridaehost-shifting.

Objectives: Photoplethysmography (PPG) is an established technology for detecting pulse rate and pulse wave irregularities. However, whether temporal variations in pulse wave amplitudes, reflecting a combination of acute hemodynamic or autonomic responses to changes in overall vascular function, carry prognostic information remains unclear. To quantify nocturnal temporal pulse wave amplitude (PWA) attenuations and evaluate its association with long-term cardiovascular (CV) events in a large, racially diverse sample of men and women. Methods: Temporal PWA attenuations were determined based on the slopes between the upper and lower envelopes of PPGs derived from overnight polysomnography of 1957 participants (899 men, 1058 women, mean age 68.2 ± 9.1 years) of the Multi-Ethnic Study of Atherosclerosis. The nocturnal PWA attenuation index was defined as the cumulative duration of all PWA attenuation events relative to total sleep duration. Results: Nocturnal PWA attenuation index was greater in men than in women by almost 13% (16.3 ± 8.9% vs. 14.4 ± 7.9%, p < 0.001). The nocturnal PWA attenuation index was highest in Chinese-American participants (17.9 ± 9.2%) and lowest in African-Americans (13.5 ± 8.1%). During a median follow-up of 4.9 years, 94 CV events occurred. In multivariable Cox proportional hazard analysis adjusted for typical confounders, the nocturnal PWA attenuation index

Background: Fear of SARS-CoV-2 infection and lockdown measures may have an impact on health care utilization particularly for people with chronic diseases. We investigated changes in outpatient utilization behavior in pandemic phases among people with selected chronic diseases in Germany. Methods: The nationwide telephone surveys GEDA 2019/2020-EHIS (April 2019 to September 2020) and GEDA 2021 (July to December 2021) covered 4 out of 7 pandemic phases from the pre-pandemic to the 4th pandemic wave. Data on hypertension, major cardiovascular diseases (CVD) and diabetes in the past 12 months and visiting a general practitioner (GP) or a specialist (excluding dentist) in the past 4 weeks was collected using a standardized questionnaire. Proportions and odds ratios were derived from logistic regression models adjusted for age, sex, education and federal state. Results: Among 27,967 participants aged ≥16 years, 8,449, 1,136 and 2,497 individuals had hypertension, major CVD and diabetes. Participants with these chronic diseases visited a GP or specialist significantly more often than the overall study population, irrespective of pandemic phases. Compared to the pre-pandemic phase, a significant reduction in specialist-visiting was found in the 1st pandemic wave among people with hypertension (34.3% vs. 24.1%), major CVD (41.9% vs. 25.6%) and diabetes (39.5% vs. 25.5%). GP-visiting was lower only among people with hypertension (53.0% vs. 46.0%). No difference in GP or specialist visiting was found in the 4th pandemic wave compared to the pre-pandemic phase. Conclusions: The observed decrease particularly in specialist utilization among people with the selected chronic diseases at the beginning of the pandemic was not observed for the second half of 2021 despite the ongoing pandemic. Further studies are required to examine whether the temporary changes in the utilization of ambulatory health care have affected the disease management of people with chronic diseases.

The study enrolled 284 patients with chronic hepatitis B virus infection. Participants included people with mild fibrotic lesions (32.5%), moderate to severe fibrotic lesions (27.5%), cirrhotic lesions (22%), hepatocellular carcinoma (HCC) in 5%, and people with no fibrotic lesions in 13%. Eleven SNPs within DIO2, PPARG, ATF3, AKT, GADD45A, and TBX21 were genotyped by mass spectrometry. The rs225014 TT (DIO2) and rs10865710 CC (PPARG) genotypes were independently associated with susceptibility to advanced liver fibrosis. However, cirrhosis was more prevalent in individuals with the GADD45A rs532446 TT and ATF3 rs11119982 TT genotypes. In addition, the rs225014 CC variant of DIO2 was more frequently found in patients with a diagnosis of HCC. These findings suggest that the above SNPs may play a role in HBV-induced liver damage in a Caucasian population.

Supplemental Figure 1. Chemical structures of non-FDA approved compounds used in the Study; Supplemental Figure 2. Effect of drugs on growth and target phosphorylation; Supplemental Figure 3. mTOR inhibition does not show dose dependent Radiosensitization; Supplemental Figure 4. MEK162 + RT abrogate spheroid regrowth; Supplemental Figure 5. MEK162 radiosensitizes GBM8 primary spheroid culture and increases γH2AX levels; Supplemental Figure 6. MEK162 abrogates BrdU washout and increases sub-G1 accumulation of BrdU+ cells; Supplemental Figure 7. MEK162 + RT in vivo; Supplemental Table 1: Antibodies used; Supplemental Table 2: Gene signature MEK+RT response

Glioblastoma (GBM) is a highly aggressive and lethal brain cancer type. PI3K and MAPK inhibitors have been studied preclinically in GBM as monotherapy, but not in combination with radiotherapy, which is a key component of the current standard treatment of GBM. In our study, GBM cell lines and patient representative primary cultures were grown as multicellular spheroids. Spheroids were treated with a panel of small-molecule drugs including MK2206, RAD001, BEZ235, MLN0128, and MEK162, alone and in combination with irradiation. Following treatment, spheroid growth parameters (growth rate, volume reduction, and time to regrow), cell-cycle distribution and expression of key target proteins were evaluated. In vivo, the effect of irradiation (3 × 2 Gy) without or with MEK162 (50 mg/kg) was studied in orthotopic GBM8 brain tumor xenografts with endpoints tumor growth and animal survival. The MAPK-targeting agent MEK162 was found to enhance the effect of irradiation as demonstrated by growth inhibition of spheroids. MEK162 downregulated and dephosphorylated the cell-cycle checkpoint proteins CDK1/CDK2/WEE1 and DNA damage response proteins p-ATM/p-CHK2. When combined with radiation, this led to a prolonged DNA damage signal. In vivo data on tumor-bearing animals demonstrated a significantly reduced growth rate, increased growth delay, and prolonged survival time. In addition, RNA expression of responsive cell cultures correlated to mesenchymal stratification of patient expression data. In conclusion, the MAPK inhibitor MEK162 was identified as a radiosensitizer in GBM spheroids in vitro and in orthotopic GBM xenografts in vivo. The data are supportive for implementation of this targeted agent in an early-phase clinical study in GBM patients. Mol Cancer Ther; 17(2); 347–54. ©2017 AACR.See all articles in this MCT Focus section, “Developmental Therapeutics in Radiation Oncology.”

Ultrashort near-infrared femtosecond laser pulses have become the tool of choice for high-precision processing of transparent ultrawide bandgap materials, ranging from material ablation, amorphization, waveguide writing to optical data storage. The processing precision with ultrashort laser pulses is fundamentally limited in the lateral direction by diffraction, while self-absorption and self-reflection are limiting the achievable depth. In this chapter, we present one of the possible pathways to overcome these limits by utilizing temporal pulse-shaping technology. In the following, we review and discuss the main light-matter interaction mechanisms, multiphoton and avalanche excitation, and how ultrashort and temporally shaped femtosecond laser pulses address them differently, allowing the control over the spatial carrier distribution and the subsequent material processing. We demonstrate the potential of temporal pulse shaping as a tool for controlled nanostructuring below the typical limits by discussing our in situ and postmortem experimental and numerical studies on the spatial distribution of laser excitation in water, high-aspect-ratio structuring of fused silica, and the optoporation of cells.

No abstract available

Supplementary Data from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial

Purpose:In a post hoc analysis of the CATNON trial (NCT00626990), we explored whether adding temozolomide to radiotherapy improves outcome in patients with IDH1/2 wildtype (wt) anaplastic astrocytomas with molecular features of glioblastoma [redesignated as glioblastoma, isocitrate dehydrogenase–wildtype (IDH-wt) in the 2021 World Health Organization (WHO) classification of central nervous system tumors].Patients and Methods:From the randomized phase III CATNON study examining the addition of adjuvant and concurrent temozolomide to radiotherapy in anaplastic astrocytomas, we selected a subgroup of IDH1/2wt and H3F3Awt tumors with presence of TERT promoter mutations and/or EGFR amplifications and/or combined gain of chromosome 7 and loss of chromosome 10. Molecular abnormalities including MGMT promoter methylation status were determined by next-generation sequencing, DNA methylation profiling, and SNaPshot analysis.Results:Of the 751 patients entered in the CATNON study, 670 had fully molecularly characterized tumors. A total of 159 of these tumors met the WHO 2021 molecular criteria for glioblastoma, IDH-wt. Of these patients, 47 received radiotherapy only and 112 received a combination of radiotherapy and temozolomide. There was no added effect of temozolomide on either overall survival [HR, 1.19; 95% confidence interval (CI), 0.82–1.71] or progression-free survival (HR, 0.87; 95% CI, 0.61–1.24). MGMT promoter methylation was prognostic for overall survival, but was not predictive for outcome to temozolomide treatment either with respect to overall survival or progression-free survival.Conclusions:In this cohort of patients with glioblastoma, IDH-wt temozolomide treatment did not add benefit beyond that observed from radiotherapy, regardless of MGMT promoter status. These findings require a new well-powered prospective clinical study to explore the efficacy of temozolomide treatment in this patient population.

Supplementary Figure from Temozolomide and Radiotherapy versus Radiotherapy Alone in Patients with Glioblastoma, IDH-wildtype: Post Hoc Analysis of the EORTC Randomized Phase III CATNON Trial

Older cancer patients are disproportionally affected by the Coronavirus 19 (COVID-19) pandemic. A higher rate of death among the elderly and the potential for long-term disability have led to fear of contracting the virus in these patients. This fear can, paradoxically, cause delay in diagnosis and treatment that may lead to a poor outcome that could have been prevented. Thus, physicians should devise a policy that both supports the needs of older patients during cancer treatment, and serves to help them overcome their fear so they seek out to cancer diagnosis and treatment early. A combination of telemedicine and a holistic approach, involving prayers for older cancer patients with a high level of spirituality, may improve vaccination rates as well as quality of life during treatment. Collaboration between health care workers, social workers, faith-based leaders, and cancer survivors may be crucial to achieve this goal. Social media may be an important component, providing a means of sending the positive message to older cancer patients that chronological age is not an impediment to treatment.

Background Intensity-modulated helical tomotherapy (HT) is a promising technique in preparation for bone marrow transplantation. Nevertheless, radiation-sensitive organs can be substantially compromised due to suboptimal delivery techniques of total body irradiation (TBI). To reduce the potential burden of radiation toxicity to organs at risk (OAR), high-quality coverage and homogeneity are essential. We investigated dosimetric data from kidney, lung and thorax, liver, and spleen in relation to peripheral blood kinetics. To further advance intensity-modulated total body irradiation (TBI), the potential for dose reduction to lung and kidney was considered in the analysis. Patients and methods 46 patients undergoing TBI were included in this analysis, partially divided into dose groups (2, 4, 8, and 12 Gy). HT was performed using a rotating gantry to ensuring optimal reduction of radiation to the lungs and kidneys and to provide optimal coverage of other OAR. Common dosimetric parameters, such as D05, D95, and D50, were calculated and analysed. Leukocytes, neutrophils, platelets, creatinine, GFR, haemoglobin, overall survival, and graft-versus-host disease were related to the dosimetric evaluation using statistical tests. Results The mean D95 of the lung is 48.23%, less than half the prescribed and unreduced dose. The D95 of the chest is almost twice as high at 84.95%. Overall liver coverage values ranged from 96.79% for D95 to 107% for D05. The average dose sparing of all patients analysed resulted in an average D95 of 68.64% in the right kidney and 69.31% in the left kidney. Average D95 in the spleen was 94.28% and D05 was 107.05%. Homogeneity indexes ranged from 1.12 for liver to 2.28 for lung. The additional significance analyses conducted on these blood kinetics showed a significant difference between the 2 Gray group and the other three groups for leukocyte counts. Further statistical comparisons of the dose groups showed no significant differences. However, there were significant changes in the dose of OAR prescribed with dose sparing (e.g., lung vs. rib and kidney). Conclusion Using intensity-modulated helical tomotherapy to deliver TBI is a feasible method in preparation for haematopoietic stem cell transplantation. Significant dose sparing in radiosensitive organs such as the lungs and kidneys is achievable with good overall quality of coverage. Peripheral blood kinetics support the positive impact of HT and its advantages strongly encourage its implementation within clinical routine.

editorial research support, n.i.h., extramural research support, non-u.s. gov't 2023 Mar 01 2022 12 01 imported

editorial research support, non-u.s. gov't 2022 Oct 2022 08 08 imported

Intergroup conflicts can be triggered and perpetuated by collective perceptions of injustice. In two experiments, we applied the qualifying of subjective justice views, a justice-focused intervention initially introduced to resolve interpersonal conflicts, and evaluated whether it can mitigate intergroup conflicts. This intervention included explicating opposing justice perceptions, explaining the dilemma structure of justice conflicts, and emphasizing that each conflict party applies different justice standards in different situations. In a realistic conflict setting, among advantaged group members, the intervention enhanced the willingness to pay monetary concessions to the out-group. This effect was mediated through an enhanced understanding of the justice dilemma (Study 2) and legitimacy judgments of the out-group’s justice claim (Studies 1 and 2). Furthermore, effects of the justice-focused intervention were compared to those of empathy induction as a benchmark to evaluate the effectiveness. The comparison provided additional evidence for the effectiveness of the justice-focused intervention to mitigate intergroup conflicts.

Context Whether playing position influences injury in male academy soccer players (ASPs) is unclear. Objective To determine if playing position was associated with injury in ASPs. Design Descriptive epidemiology study. Setting English, Spanish, Uruguayan, and Brazilian soccer academies. Patients or Other Participants A total of 369 ASPs from the under-14 to under-23 age groups, classified as post-peak height velocity using maturity offset, and grouped as goalkeepers, lateral defenders, central defenders, lateral midfielders, central midfielders, or forwards. Main Outcome Measure(s) Injuries were recorded prospectively over 1 season. Injury prevalence proportion (IPP), days missed, and injury incidence rate (IIR, injuries/1000 training or match hours, n = 116) were analyzed according to playing position. Results No association with playing position was observed for any injury type or location regarding IPP (P ≥ .089) or days missed (P ≥ .235). The IIR was higher in central defenders than in lateral defenders for general (9.30 versus 4.18 injuries/1000 h, P = .009), soft tissue (5.14 versus 1.95 injuries/1000 h, P = .026), and ligament or tendon injuries (2.69 versus 0.56 injuries/1000 h, P = .040). The central versus lateral or forward positions were not associated with IPP (P ≥ .051) or days missed (P ≥ .083), but general IIR was greater in the central position than the lateral or forward positions (8.67 versus 6.12 injuries/1000 h, P = .047). Conclusions Academy soccer players' playing positions were not associated with IPP or days missed, but the higher general, soft tissue, and ligament or tendon IIRs in central defenders suggest that this position warrants specific attention regarding injury-prevention strategies. These novel findings highlight the importance of considering training or match exposure when investigating the influence of playing position on injury in ASPs.

Chronic liver diseases, resulting from chronic injuries of various causes, lead to cirrhosis with life-threatening complications including liver failure, portal hypertension, hepatocellular carcinoma. A key unmet medical need is robust non-invasive biomarkers to predict patient outcome, stratify patients for risk of disease progression and monitor response to emerging therapies. Quantitative imaging biomarkers have already been developed, for instance, liver elastography for staging fibrosis or proton density fat fraction on magnetic resonance imaging for liver steatosis. Yet, major improvements, in the field of image acquisition and analysis, are still required to be able to accurately characterize the liver parenchyma, monitor its changes and predict any pejorative evolution across disease progression. Artificial intelligence has the potential to augment the exploitation of massive multi-parametric data to extract valuable information and achieve precision medicine. Machine learning algorithms have been developed to assess non-invasively certain histological characteristics of chronic liver diseases, including fibrosis and steatosis. Although still at an early stage of development, artificial intelligence-based imaging biomarkers provide novel opportunities to predict the risk of progression from early-stage chronic liver diseases toward cirrhosis-related complications, with the ultimate perspective of precision medicine. This review provides an overview of emerging quantitative imaging techniques and the application of artificial intelligence for biomarker discovery in chronic liver disease. journal article review 2022 Jun 2022 02 09 imported

Introduction: Sleep-disordered breathing (SDB) is present in 21–74% of all patients with atrial fibrillation (AF). Treatment of SDB by positive airway pressure may help to prevent recurrence of AF after electrical cardioversion and help to improve AF ablation success rates in non-randomized studies. Areas covered: In this review, the current understanding of the atrial arrhythmogenic pathophysiology of SDB is summarized, and diagnostic and therapeutic challenges in AF patients are discussed. Current international recommendations are presented, and a comprehensive literature search is undertaken. Expert opinion: AF patients with SDB rarely report SDB-related symptoms such as daytime sleepiness. Therefore, systematic home sleep testing evaluation should be considered for all patients eligible for rhythm control strategy. A close interdisciplinary collaboration between the electrophysiologist/cardiologist, nurses and sleep-specialists are required for the management of SDB in AF patients. An arrhythmia-orientated assessment of SDB may better quantify SDB-related AF risk in an individual patient and may help to better guide targeted and personalized SDB treatment in AF patients as a component of rhythm and symptom control strategies. Finally, randomized controlled trials are needed to confirm the relationship between SDB and AF, and the benefits of routine testing and treatment of SDB in AF patients.

The detection and quantification of soy protein is important for food allergen management and identifying the presence of undeclared soy proteins. Heat processing and matrix interactions can affect the accuracy of allergen detection methods. The sensitivity of enzyme-linked immunosorbent assay methods can be compromised if protein epitopes are modified during processing. Therefore, a mass spectrometry (MS)-based method was evaluated for the recovery of total soy protein in incurred matrices. MS-based quantification of total soy protein was assessed by using a combination of external and internal standards. The reproducibility of the standard curves was investigated by comparing within-day and among-day variation. Incurred samples were prepared using bread and frankfurters as model food matrices. Several soy-derived ingredients were used to prepare the matrices with varying levels of soy protein (1, 10, 50, or 100 ppm of total soy protein). A pooled standard curve was used to estimate the total soy protein concentration of the incurred food matrices and the percent total protein recovery. The variation of replicate standard curves between days and among all days was not significant. The differences in slopes obtained from replicate standards run on different days were minimal. The most influential factor on the quantitative protein recovery in incurred samples was the effect of the physical matrix structure on protein extraction. The lowest percent protein recoveries, less than 50%, were calculated for uncooked matrices. The cooked matrices had percentage recoveries between 50 and 150% for all total soy protein levels. Other factors, such as type of ingredient, were determined to be not as impactful on recovery. The MS method described in this study was able to provide sensitive detection and accurate quantification of total soy protein from various soy-derived ingredients present in processed food matrices.

In six studies, we consistently observed costly third-party punishment (3PP) to decrease under ambiguity of the norm violation. Our research suggests that, under ambiguity, some people experience concerns about punishing unfairly. Those with higher (vs. lower) other-oriented justice sensitivity (Observer JS) reduced 3PP more pronouncedly (in Studies 1–3 and 4b, but not replicated in Studies 4–5). Moreover, those who decided to resolve the ambiguity (hence, removing the risk of punishing unfairly) exceeded the 3PP observed under no ambiguity (Study 4). However, we did not consistently observe these concerns about punishing unfairly to affect 3PP (Studies 4–5). We further considered whether people could use ambiguity as justification for remaining passive—thus, avoiding the costs of 3PP. We did not find conclusive evidence supporting this notion. Taken together, ambiguity entails a situational boundary of 3PP that sheds light on the prevalence of this behavior and, potentially, on its preceding decision-making.

Individuals differ systematically in how much they are concerned with matters of justice or injustice. So far, in various domains of life, such as romantic relationships, work, and school contexts, dispositional justice sensitivity has been found to be a powerful predictor of individual-level processing and interpersonal behaviors. Yet, matters of justice and injustice often materialize at the group level, especially when conflicts about status, rights, and resources occur between groups. Here, we propose a theoretical framework to understand how different facets of justice sensitivity (i.e., victim, beneficiary/perpetrator, and observer sensitivities) are relevant for group-level processes in intergroup contexts. Integrating research on justice sensitivity and intergroup conflict, we develop several propositions regarding how and under which conditions justice sensitivity influences intergroup experiences, attitudes, and behaviors. We selectively review the existing empirical evidence that can speak to the validity of these propositions, and outline future research that can test our propositions.

We report chirality detection of structural isomers in a gas phase mixtureusing nanosecond photoelectron circular dichroism (PECD). Combiningpulsed molecular beams with high-resolution resonance enhancedmulti-photon ionization (REMPI) allows specific isolated transitionsbelonging to distinct components in the mixture to be targeted

BACKGROUND AND AIMS: Hepatitis C is poorly documented in migrants. The published studies mainly concern the screening in this population and are limited to some countries in Europe and North America. This study aimed to evaluate the characteristics and care of chronic hepatitis C in this population compared to the nonmigrant population, in the era of direct-acting antivirals (DAAs). METHOD: We performed a retrospective analysis based on data presented at the multidisciplinary team meetings of our tertiary care center between 2015 and 2019. RESULTS: We included 277 migrant- and 1390 nonmigrant patients mono-infected with hepatitis C virus (HCV) and treated with DAAs. The majority of the migrants were from Eastern European countries. In multivariable analysis, BMI classes associated with more obesity (OR = 1.84; 95% CI, 1.37-2.49; P < 0.001) and therapeutic patient education (OR = 3.91; 95% CI, 2.38-6.49; P < 0.001) were positively associated with migrant status, whereas age (OR = 0.92; 95% CI, 0.90-0.94; P < 0.001), female gender (OR = 0.46; 95% CI, 0.28-0.74; P = 0.002), modes of contamination with less drug use, transfusion history or nosocomial risk, as well more unknown mode (OR = 0.70; 95% CI, 0.50-0.96; P = 0.031), alcohol consumption (OR = 0.48; 95% CI, 0.29-0.73; P = 0.001), types of structures with less care in a general hospital or health network of general practitioners and more care in a university hospital or primary addictology center (OR = 0.78; 95% CI, 0.60-0.99; P = 0.046) and opioid substitution therapy (OR = 0.25; 95% CI, 0.08-0.68; P = 0.008) were negatively associated with migrant status. The substained virologic response 12 was close to 97% in both groups. CONCLUSION: Despite multiple differences in characteristics and therapeutic care between the two populations, the chances of healing hepatitis C were the same among migrant- compared with nonmigrant patients.