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It is hypothesized that the ability to discriminate between threat and safety is impaired in individuals with high dispositional negativity, resulting in maladaptive behavior. A large body of research investigated differential learning during fear conditioning and extinction protocols depending on individual differences in intolerance of uncertainty (IU) and trait anxiety (TA), two closely-related dimensions of dispositional negativity, with heterogenous results. These might be due to varying degrees of induced threat/safety uncertainty. Here, we compared two groups with high vs. low IU/TA during periods of low (instructed fear acquisition) and high levels of uncertainty (delayed non-instructed extinction training and reinstatement). Dependent variables comprised subjective (US expectancy, valence, arousal), psychophysiological (skin conductance response, SCR, and startle blink), and neural (fMRI BOLD) measures of threat responding. During fear acquisition, we found strong threat/safety discrimination for both groups. During early extinction (high uncertainty), the low IU/TA group showed an increased physiological response to the safety signal, resulting in a lack of CS discrimination. In contrast, the high IU/TA group showed strong initial threat/safety discrimination in physiology, lacking discriminative learning on startle, and reduced neural activation in regions linked to threat/safety processing throughout extinction training indicating sustained but non-adaptive and rigid responding. Similar neural patterns were found after the reinstatement test. Taken together, we provide evidence that high dispositional negativity, as indicated here by IU and TA, is associated with greater responding to threat cues during the beginning of delayed extinction, and, thus, demonstrates altered learning patterns under changing environments.

Objectives To evaluate the feasibility of Doppler-ultrasound (DUS)-gated 4D flow MRI of the fetal great thoracic vessels at 3T in a clinical setting. Methods Sixteen consecutive fetuses (range 30+4–38+5 weeks) with (n = 11) and without (n = 5) cardiovascular anomalies underwent 4D flow MRI of the great thoracic vessels at 3T. Direct fetal cardiac gating was obtained using a MR-compatible DUS device. 4D flow MRI–based visualisation and quantification of four target regions (ascending aorta (AAo), descending aorta (DAo), main pulmonary artery (MPA), and ductus arteriosus (DA)) were performed using dedicated software. Results Fetal 4D flow MRI of the great thoracic vessels was successful in 12/16 fetuses (75%) by adopting clinical 4D flow MR protocols in combination with direct fetal cardiac DUS-gating. Four datasets were excluded due to artefacts by fetal movement or maternal breathing. 4D flow MRI–derived time-velocity curves revealed typical arterial blood flow patterns in the aorta. 4D flow quantification was achieved for the pre-defined target regions. Average velocity and flow volume were 21.1 ± 5.2 cm/s and 6.0 ± 3.1 mL/s in the AAo, 24.3 ± 6.7 cm/s and 8.4 ± 3.7 mL/s in the DAo, 21.9 ± 6.4 cm/s and 7.8 ± 4.2 mL/s in the MPA, and 23.4 ± 4.7 cm/s and 5.9 ± 3.6 mL/s in the DA, respectively. Conclusions Combination of DUS-gating of the fetal heart and 4D flow MRI allows comprehensive visualisation and quantification of haemodynamics in the fetal great thoracic vessels. DUS-gated fetal 4D flow MRI may provide a new diagnostic approach for prenatal assessment of blood flow haemodynamics. Key Points • Fetal cardiac Doppler-ultrasound (DUS) gating and 4D flow MRI can be successfully combined. • DUS-gated fetal 4D flow MRI allowed visualisation and evaluation of streamline directionality, illustration of blood flow variations, and pulsatile arterial waveforms in the target vessels. • 4D flow MRI–based visualisation and quantification of the fetal great thoracic vessels were successful and flow metrics agreed with echocardiographic reference values.

High-intensity interval training (HIIT) has been shown to improve cardiorespiratory fitness (CRF) and health-related outcomes in various chronic diseases, including cancer. However, data on feasibility and efficacy of HIIT in advanced cancer patients are still sparse, presumably because of safety concerns, like suspected immunosuppression after vigorous exercise. This randomized, sham-intervention controlled study aimed to investigate feasibility, safety, and preliminary efficacy of very low-volume HIIT (LOW-HIIT) in advanced cancer patients.Twenty-seven patients (55.4 ± 13.2 yr) with different advanced cancers (Union for International Cancer Control [UICC] III/IV) were randomly allocated to LOW-HIIT ( n = 13), consisting of 5 × 1 min cycle ergometer intervals (14 min per session total duration) at 80% to 95% HR peak (two sessions per week for 12 wk), or a sham intervention ( n = 14) performing light physical mobilization exercises (SHAM). Primary outcomes were attrition and attendance rates, with values of ≤25% and ≥80%, respectively, considered acceptable. Secondary outcomes were safety, protocol fidelity, physiological (including CRF measures) and patient-reported outcomes (including fatigue and quality of life).One of 13 patients (8%) receiving LOW-HIIT dropped out. Mean attendance rate was ~93%. The prescribed minimum exercise intensity was consistently reached by all patients. Low-volume HIIT was well tolerated and not associated with any serious adverse event nor with increased infection susceptibility. There were no biochemical signs of acute immunosuppression after LOW-HIIT. Contrarily, differentiation and degranulation of natural killer cells was acutely increased postexercise. Low-volume HIIT improved CRF measures including peak oxygen uptake, self-reported fatigue, physical, and social functioning. No significant changes occurred in the SHAM group.Low-volume HIIT can be regarded as feasible and safe in advanced cancer patients. Our preliminary data indicate favorable acute effects on NK-cells and beneficial chronic adaptations in CRF, fatigue, and aspects of quality of life.

During the COVID-19 pandemic, physical distancing measures to prevent transmission of the virus have been implemented. The effect of physical distancing measures on loneliness especially for vulnerable groups remained unclear. Thus, we aimed to investigate loneliness in relation with depressive symptoms among lesbian, gay, bisexual, trans, inter, asexual, and queer (LGBT) persons compared with cis-heterosexual persons during the pandemic. We conducted an online survey during the first two waves of the COVID-19 pandemic in Germany. The survey contained self-categorizations regarding sexual orientation and gender identity, questions on loneliness, social contacts, depressive symptoms, and healthcare. Descriptive and regression analysis and propensity score matching across cohorts was conducted using R; 2641 participants took part in first wave of the survey and 4143 participants in the second wave. The proportion of lonely people was higher in the second wave compared with the first wave. LGBT persons were more lonely than cis-heterosexual persons. In both waves, being LGBT was associated with depressive symptoms, but loneliness mediated the effect, even when adjusting for social contacts. Psychologists and other practitioners should be aware that LGBT clients might have an increased risk for loneliness and depressive symptoms and of the potential burden of the pandemic measures.

Disclaimer In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Purpose Fixed-dose and body mass index (BMI)–based enoxaparin regimens provide inadequate venous thromboembolism (VTE) prophylaxis for many trauma patients. The purpose of this study was to evaluate the effectiveness of a novel blood volume (BV)–based enoxaparin guideline vs a historical BMI-based guideline for VTE prophylaxis in trauma patients. Methods This was a retrospective pre/post study completed at a large academic level 1 trauma center. All adult trauma patients admitted from October through December 2019 and August through October 2020 who received prophylactic enoxaparin per guideline were included. The BV dosing was as follows: patients with a BV of 3 to 4.9 L received enoxaparin 30 mg every 12 hours, those with a BV of 5 to 6.9 L received 40 mg every 12 hours, and those with a BV of ≥7 L received 60 mg every 12 hours. The primary outcome was the percentage of patients who attained a target anti–factor Xa (anti-Xa) postdosing level at the first steady-state assessment (0.2 to 0.5 IU/mL). Results A total of 241 patients (99 for the BMI group and 142 for the BV group) were included. The study groups had a median age of 38 vs 42 years, a mean BMI of 27.4 vs 27.7 kg/m 2, and a mean BV of 5.1 vs 5.1 L, respectively. A total of 63 patients (62.6%) in the BMI group attained target anti-Xa levels compared to 115 patients (81%) in the BV group (P = 0.008). In multivariate regression, the BV-based guideline was the only variable associated with attainment of target anti-Xa levels (adjusted odds ratio, 2.02; P = 0.01). Clinically relevant bleeding and VTE rates were similar between the groups. Conclusion Dosing prophylactic enoxaparin using a BV-based dosing guideline significantly increased attainment of target anti-Xa levels.

Hospital admissions due to acute cardiovascular events dropped during the COVID-19 pandemic in the general population; however, evidence for residents of long-term care facilities (LTCF) is sparse. We investigated rates of hospital admissions and deaths due to myocardial infarction (MI) and stroke in LTCF residents during the pandemic. Our nationwide cohort study used claims data. The sample comprised 1,140,139 AOK-ensured LTCF residents over 60 years of age (68.6% women; age 85.3 ± 8.5 years) from the largest statutory health insurance in Germany (AOK), which is not representative for all LTCF residents. We included MI and stroke admission and compared numbers of in-hospital deaths from January 2020 to end of April 2021 (i.e., during the first three waves of the pandemic) with the number of incidences in 2015–2019. To estimate incidence risk ratios (IRR), adjusted Poisson regression analyses were applied. During the observation period (2015–2021), there were 19,196 MI and 73,953 stroke admissions. MI admissions declined in the pandemic phase by 22.5% (IRR = 0.68 [CI 0.65–0.72]) compared to previous years. This decline was slightly more pronounced for NSTEMI than for STEMI. MI fatality risks remained comparable across years (IRR = 0.97 [CI95% 0.92–1.02]). Stroke admissions dropped by 15.1% (IRR = 0.75 [CI95% 0.72–0.78]) in the pandemic. There was an elevated case fatality risk for haemorrhagic stroke (IRR = 1.09 [CI95% 1.03–1.15]) but not for other stroke subtypes compared to previous years. This study provides first evidence of declines in MI and stroke admissions and in-hospital deaths among LTCF residents during the pandemic. The figures are alarming given the acute nature of the conditions and the vulnerability of the residents.

Maintaining mobility with increasing age depends on personal, social and environmental factors, but the understanding of their complex interplay remains limited. Considering the comprehensive concept of Life-space mobility (LSM), we aim to illustrate the synergistic or antagonistic interplay of personal, social and environmental factors for life-space mobility (LSM) of older adults living in rural areas. Semi-structured interviews with twelve older adults (74–95 years) from a particularly rural area in Germany were conducted alongside the validation study of the German version of the Life-Space Assessment (DRKS00019023). To analyze interview transcripts methods of qualitative content analysis were applied using MAXQDA 2020. Participants were additionally characterized with assessments of LSM, everyday functioning, quality of life and balance confidence were carried out. Eight participants reported restricted LSM. Qualitative analysis displayed that difficulties visiting healthcare services were related to accessible information and dependence on being driven there. Additionally, factors cancelled each other out, e.g., the motivation to go out was facilitated by modernized sidewalks but subverted by the absence of social contacts. Findings related to social and environmental factors turned out to be ambivalent. For instance, the spouse who helped his wife to be mobile outdoors also undermined her motivation to go out. Results reveal various forms of interplay of personal, social and environmental factors providing an enriched understanding of emerging barriers to LSM as well as resource allocation to maintain LSM in old age.