Publications by authors named "Thomas Lang"

277 Publications

Intraoperative completion studies in carotid endarterectomy: systematic review and meta-analysis of techniques and outcomes.

Ann Transl Med 2021 Jul;9(14):1201

Department for Vascular and Endovascular Surgery, Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.

Background: Declining perioperative stroke and death rates over the past 3 decades have been paralleled by an increasing use of intraoperative completion studies (ICS) following carotid endarterectomy (CEA). Techniques applied include angiography, intraoperative duplex ultrasound (IDUS), flowmetry, and angioscopy. This systematic review and meta-analysis is aiming on providing an overview of techniques and corresponding outcomes.

Methods: A PubMed based systematic literature review comprising the years 1980 through 2020 was performed using predefined keywords to identify articles on different ICS techniques. Pooled analyses and meta-analyses estimating risk ratios (RR) and 95% confidence intervals (CI) were performed to compare outcomes of different ICS modes to nonapplication of any ICS. I values were assessed to quantify study heterogeneities.

Results: Identification of 34 studies including patients undergoing CEA with angiography (n=53,218), IDUS (n=20,030), flowmetry (n=16,812), and angioscopy (n=2,291). Corresponding rates of perioperative stroke were 1.5%, 1.8%, 3.6%, and 1.5%, perioperative stroke or death occurred in 1.7%, 1.9%, 2.2%, and 2.0%. Intraoperative surgical revision rates were 6.2%, 5.9%, and 7.9% after CEA with angiography, IDUS, and angioscopy, respectively. Compared to nonapplication of any ICS, the pooled analysis revealed angiography to be significantly associated with lower rates of stroke (RR 0.47; 95% CI, 0.36-0.62; P<0.0001) and stroke or death (RR 0.76; 95% CI, 0.70-0.83; P<0.0001). IDUS was significantly associated with lower rates of stroke (RR 0.56; 95% CI, 0.43-0.73; P<0.0001) and stroke or death (RR 0.83; 95% CI, 0.74-0.93; P=0.0018), whereas angioscopy showed a significant association with a lower stroke rate (RR 0.48; 95% CI, 0.033-0.68; P=0.0001), but no effect on the combined stroke or death rate. Angioscopy was associated with a higher intraoperative revision rate compared to angiography (RR 1.29; 95% CI, 1.07-1.54; P=0.006). The meta-analyses confirmed lower perioperative stroke or death rates for angiography (RR 0.83; 95% CI, 0.76-0.91) and IDUS (RR 0.86; 95% CI, 0.76-0.98) compared to non-application of any ICS, whereas flowmetry showed no significant association.

Conclusions: This study represents the first systematic literature review and meta-analysis on usage of ICSs in CEA. Data strongly indicate a significant beneficial effect of angiography, IDUS, and angioscopy on perioperative CEA outcomes. Any carotid surgeon should consider implementation of ICSs in his routine armamentarium.
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http://dx.doi.org/10.21037/atm-20-2931DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8350645PMC
July 2021

Restoration-oriented stressors of bereavement.

Anxiety Stress Coping 2021 Jul 31:1-15. Epub 2021 Jul 31.

Department of Clinical Psychology and Experimental Psychopathology, Faculty of Behavioral and Social Sciences, University of Groningen, Groningen, The Netherlands.

Background And Objectives: The Dual Process Model of Coping with Bereavement holds that bereaved people who respond flexibly to loss-oriented stressors (i.e., relating to the loss; to the deceased person) and restoration-oriented stressors (i.e., secondary to loss; daily-life changes, taking on new roles) adapt better to bereavement. Despite growing interest in the Dual Process Model, systematic analyses of the prevalence, characteristics, and correlates of restoration-oriented stressors are lacking. Therefore, we aimed to chart restoration-oriented stressors and their relationship with post-loss adaptation.

Design And Methods: A community sample of 181 bereaved adults (63% women) completed the 20-item expert-construed Restoration-Oriented Stressors Inventory (ROSI) and questionnaires assessing background characteristics, worry, and prolonged grief and depression symptoms.

Results: Main findings were that younger people, and those who lost a parent, partner, or child (vs. other relationship) experienced more restoration-oriented stressors and appraised these as more stressful. Stressors' perceived stressfulness, but not their quantity, related positively to worry. Perceived stressfulness predicted prolonged grief and depression symptoms beyond background characteristics, worry, and the number of stressors.

Conclusion: Restoration-oriented stressors and their appraisal vary and relate to coping and post-loss mental health. Future research should clarify temporal interrelations between stressors, coping mechanisms, and outcomes.
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http://dx.doi.org/10.1080/10615806.2021.1957849DOI Listing
July 2021

Quantum simulation of 2D antiferromagnets with hundreds of Rydberg atoms.

Nature 2021 07 7;595(7866):233-238. Epub 2021 Jul 7.

Laboratoire Charles Fabry, Institut d'Optique Graduate School, Université Paris-Saclay, CNRS, Palaiseau, France.

Quantum simulation using synthetic systems is a promising route to solve outstanding quantum many-body problems in regimes where other approaches, including numerical ones, fail. Many platforms are being developed towards this goal, in particular based on trapped ions, superconducting circuits, neutral atoms or molecules. All of these platforms face two key challenges: scaling up the ensemble size while retaining high-quality control over the parameters, and validating the outputs for these large systems. Here we use programmable arrays of individual atoms trapped in optical tweezers, with interactions controlled by laser excitation to Rydberg states, to implement an iconic many-body problem-the antiferromagnetic two-dimensional transverse-field Ising model. We push this platform to a regime with up to 196 atoms manipulated with high fidelity and probe the antiferromagnetic order by dynamically tuning the parameters of the Hamiltonian. We illustrate the versatility of our platform by exploring various system sizes on two qualitatively different geometries-square and triangular arrays. We obtain good agreement with numerical calculations up to a computationally feasible size (approximately 100 particles). This work demonstrates that our platform can be readily used to address open questions in many-body physics.
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http://dx.doi.org/10.1038/s41586-021-03585-1DOI Listing
July 2021

FSH Level and Changes in Bone Mass and Body Composition in Older Women and Men.

J Clin Endocrinol Metab 2021 Sep;106(10):2876-2889

Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA.

Context: FSH may have independent actions on bone remodeling and body fat regulation. Cross-sectionally, we have shown that serum FSH is associated with bone mineral density (BMD) and body fat in older postmenopausal women, but it remains unknown whether FSH predicts bone and fat changes.

Objective: We examined whether baseline FSH level is associated with subsequent bone loss or body composition changes in older adults.

Setting, Design, Participants: We studied 162 women and 158 men (mean age 82 ± 4 years) from the Age, Gene/Environment Susceptibility (AGES)-Bone Marrow Adiposity cohort, a substudy of the AGES-Reykjavik Study of community-dwelling older adults. Skeletal health and body composition were characterized at baseline and 3 years later.

Main Outcomes: Annualized change in BMD and body composition by dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography (QCT). Models were adjusted for serum estradiol and testosterone levels.

Results: There was no evidence for an association between baseline FSH level and change in BMD or body composition by DXA or QCT. For femoral neck areal BMD, adjusted mean difference (95% CI) per SD increase in FSH was 1.3 (-0.7 to 3.3) mg/cm2/y in women, and -0.2 (-2.6 to 2.2) mg/cm2/y in men. For visceral fat, adjusted mean difference (95% CI) per SD increase in FSH was 1.80 (-0.03 to 3.62) cm2/y in women, and -0.33 (-3.73 to 3.06) cm2/y in men.

Conclusions: Although cross-sectional studies and studies in perimenopausal women have demonstrated associations between FSH and BMD and body composition, in older adults, FSH level is not associated with bone mass or body composition changes.
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http://dx.doi.org/10.1210/clinem/dgab481DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8475206PMC
September 2021

Acute abdominal aortic occlusion-a 16-year single-center experience.

J Vasc Surg 2021 Jun 26. Epub 2021 Jun 26.

Department of Vascular and Endovascular Surgery and Munich Aortic Center, University Hospital rechts der Isar, Technical University Munich, Munich, Germany. Electronic address:

Background: Acute abdominal aortic occlusion (AAO) is a rare vascular emergency associated with high morbidity and mortality. In the present study, we analyzed the clinical management and outcomes for a consecutive patient series during a 16-year period.

Methods: We included all patients with an acute AAO and bilateral acute limb ischemia who had been treated between 2004 and 2019. Patients with dissection, aneurysm rupture, or chronic occlusive disease were excluded. The patient characteristics, surgical procedures, and outcomes were extracted retrospectively from a prospective aortic database, electronic patient files, and outpatient examination records. The extent of ischemia was classified according to the TASC II (Inter-Society Consensus for the Management of Peripheral Arterial Disease) section on acute limb ischemia. The primary endpoints were 30-day mortality (safety endpoint) and the combined 6-month amputation and/or death rate (efficacy endpoint). The follow-up outcomes, amputation rates, and 30-day complications were evaluated as secondary endpoints. The patient cohort was divided into four 4-year groups (2004-2007, 2008-2011, 2012-2015, 2016-2019) to assess the outcome changes over time. Statistical analysis included χ tests and univariate and linear regression analyses.

Results: A total of 74 patients (57% male; median age, 64.5 years) with an acute AAO were identified. Arterial thrombosis was the most common etiology (66%). The extent of ischemia was TASC I, IIa, IIb, and III in 7%, 39%, 40%, and 14%, respectively. The patient numbers had increased significantly over time (P = .016). Of the patients, 42% had undergone open transfemoral recanalization (including hybrid procedures), 35% open aortic surgery, 15% extra-anatomic bypass surgery, and 5% (four patients) endovascular therapy alone. The overall 30-day mortality rate was 23%, and the 6-month amputation and/or death rate was 43%. The 30-day mortality rate had declined significantly from 54% for 2004 to 2007 to 10% for 2011 to 2015 (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.001-0.52) and 20% for 2016 to 2019 (OR, 0.21; 95% CI, 0.05-0.90), a statistically nonsignificant trend showing that the relative decline in the use of open aortic procedures was associated with decreased 30-day mortality (P = .06). Univariate analysis indicated that elevated serum lactate on admission (OR, 3.33; 95% CI, 1.06-10.48) and an advanced stage of limb ischemia (OR, 4.33), were strongly associated with an increased 30-day mortality rate. The incidence of severe postoperative systemic complications also indicated a greater incidence of both primary endpoints. The 6-month amputation and/or mortality rates were also affected by the presence of atrial fibrillation (OR, 3.63; 95% CI, 1.34-9.79) and increased patient age (OR, 3.96; 95% CI, 1.49-10.53).

Conclusions: Acute AAO remains a life-threatening emergency. Immediate transfemoral open or endovascular techniques should be preferred, if technically possible and proper intraoperative imaging is available.
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http://dx.doi.org/10.1016/j.jvs.2021.06.021DOI Listing
June 2021

Early protein C activation is reflective of burn injury severity and plays a critical role in inflammatory burden and patient outcomes.

Burns 2021 Mar 20. Epub 2021 Mar 20.

Sutton Arthritis Research Laboratory, Kolling Institute of Medical Research, University of Sydney at Royal North Shore Hospital, St Leonards, NSW 2065, Australia.

Background: Navigating the complexities of a severe burn injury is a challenging endeavour where the natural course of some patients can be difficult to predict. Straddling both the coagulation and inflammatory cascades that feature strongly in the burns systemic pathophysiology, we propose the pleiotropic protein C (PC) system may produce a viable biomarker to assist traditional evaluation methods for diagnostic and prognostic purposes.

Methods: We enrolled 86 patients in a prospective observational cohort study. Over three weeks, serial blood samples were taken and measured for PC, activated (A)PC, their receptor endothelial protein C receptor (EPCR), and a panel of inflammatory cytokines including C-reactive protein (CRP), tumour necrosis factor-α, interleukin (IL)-1β, IL-6, IL-8, and IL-17. Their temporal trends were analysed alongside clinical factors including burn size, burn depth, presence of inhalational injury, and a composite outcome of requiring increased support.

Results: (i) APC increased from a nadir on Day 3 (2.3±2.1ng/mL vs 4.1±2.5ng/mL by Day 18, p<0.0005), only becoming appropriately correlated to PC from Day 6 onwards (r=0.412-0.721, p<0.05 for all Days 6-21). (ii) This early disturbance in the PC system was amplified in the more severe burns (≥30% total body surface area, predominantly full thickness, or with inhalational injury), which were characterised by a marked fall in PC activation (approximated by APC/PC ratio) and APC levels during Days 0-3 with low unchanged PC levels. Critically low levels of this cytoprotective agent was associated with greater inflammatory burden, as reflected by significantly elevated CRP, IL-6, and IL-8 levels in the more severe compared to less severe burns, and by negative correlations between both PC and APC with most inflammatory cytokines. (iii) Alongside clinical markers of severity at admission (burn size, burn depth, and presence of inhalational injury), only Day 0 APC/PC ratio (OR 1.048 (1.014-1.083), p=0.006), APC (OR 1.364 (1.032-1.803), p=0.029), PC (OR 0.899 (0.849-0.953), p<0.0005), and not any inflammatory cytokines were predictive markers of requiring increased support. Uniquely, decreased Day 0 PC was further individually associated with each increased total length of stay, ICU length of stay, intravenous fluid resuscitation, and total surgeries, as well as possibly mortality.

Conclusion: An early functional depletion of the cytoprotective PC system provides a physiological link between severe burns and the cytokine storm, likely contributing to worse outcomes. Our findings on the changes in APC, PC and PC activation during this pathological state support APC and PC as early diagnostic and prognostic biomarkers, and provides a basis for their therapeutic potential in severe burn injuries.
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http://dx.doi.org/10.1016/j.burns.2021.03.004DOI Listing
March 2021

Vaccines for COVID-19: An Overview.

Compend Contin Educ Dent 2021 06;42(6):298-304; quiz 305

Department of Orofacial Sciences, School of Dentistry, University of California San Francisco, San Francisco, California.

The advent of the COVID-19 pandemic in the final months of 2019 prompted an extraordinary response on the part of the scientific community, with fundamental research on the biology of the virus and the human immune response, and development of testing, therapeutics, and vaccines occurring on an unprecedentedly short timescale. Within a year after the worldwide outbreak of the disease, more than 40 vaccine candidates had emerged, with 21 candidates in phase 3 trials or already being used on an emergency basis. Many of these vaccines have involved innovative platforms. In this concise review, the authors will summarize the characteristics and performance of the leading vaccines and discuss considerations of virus mutations and asymptomatic spread that may affect the ability of the worldwide community to use these vaccines as a means to defeat the pandemic and restore pre-COVID-19 normality.
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June 2021

Transfer of exposure therapy effects to a threat context not considered during treatment in patients with panic disorder and agoraphobia: Implications for potential mechanisms of change.

Behav Res Ther 2021 07 12;142:103886. Epub 2021 May 12.

Department of Biological and Clinical Psychology/Psychotherapy, University of Greifswald, Greifswald, Germany.

Further developments of exposure-based therapy (EBT) require more knowledge about transfer of treatment to non-trained everyday contexts. However, little is known about transfer effects of EBT. Using a standardized EBT protocol in 275 patients with panic disorder and agoraphobia we investigated the transfer of EBT to a highly standardized context during a Behavioral Avoidance Test (BAT; being entrapped in a small and dark test chamber) and not part of the exposure sessions. Patients of a treatment group underwent the BATs before treatment (t1), after a preparatory treatment phase (t2), and after an agoraphobic exposure phase (t3) and were compared with wait-list control patients, who repeated BAT assessments across the same time period. We found stronger reductions in avoidance behavior, reported fear, and autonomic arousal during the BAT from t1 to t3 in the treatment group patients who were anxious during t1 relative to the anxious but untreated patients. Fear reduction was related to treatment outcome indicating the contribution of transfer effects to successful EBT. Interestingly, reduction varied for different fear response systems suggesting different processes to may be involved in transfer effects. Importantly, final BAT assessment still evoked residual fear in the treatment group as compared to BAT non-anxious control patients, suggesting limited transfer effects - one possible reason for the return of symptoms in new situations.
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http://dx.doi.org/10.1016/j.brat.2021.103886DOI Listing
July 2021

Vagal control of the heart decreases during increasing imminence of interoceptive threat in patients with panic disorder and agoraphobia.

Sci Rep 2021 04 12;11(1):7960. Epub 2021 Apr 12.

Department of Biological and Clinical Psychology, University of Greifswald, Franz-Mehring-Str. 47, 17487, Greifswald, Germany.

Theoretically, panic disorder and agoraphobia pathology can be conceptualized as a cascade of dynamically changing defensive responses to threat cues from inside the body. Guided by this trans-diagnostic model we tested the interaction between defensive activation and vagal control as a marker of prefrontal inhibition of subcortical defensive activation. We investigated ultra-short-term changes of vagally controlled high frequency heart rate variability (HRV) during a standardized threat challenge (entrapment) in n = 232 patients with panic disorder and agoraphobia, and its interaction with various indices of defensive activation. We found a strong inverse relationship between HRV and heart rate during threat, which was stronger at the beginning of exposure. Patients with a strong increase in heart rate showed a deactivation of prefrontal vagal control while patients showing less heart rate acceleration showed an increase in vagal control. Moreover, vagal control collapsed in case of imminent threat, i.e., when body symptoms increase and seem to get out of control. In these cases of defensive action patients either fled from the situation or experienced a panic attack. Active avoidance, panic attacks, and increased sympathetic arousal are associated with an inability to maintain vagal control over the heart suggesting that teaching such regulation strategies during exposure treatment might be helpful to keep prefrontal control, particularly during the transition zone from post-encounter to circa strike defense.Trial Registration Number: ISRCTN80046034.
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http://dx.doi.org/10.1038/s41598-021-86867-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8041829PMC
April 2021

Accelerated decline in quadriceps area and Timed Up and Go test performance are associated with hip fracture risk in older adults with impaired kidney function.

Exp Gerontol 2021 07 16;149:111314. Epub 2021 Mar 16.

National Institute on Aging, Intramural Research Program, Laboratory of Epidemiology and Population Sciences, Bethesda, MD, USA.

Objective: This study aimed to examine whether an accelerated decline in quadriceps cross-sectional area (CSA), attenuation (a surrogate of quality), and strength, as well as lower limb muscular function, are associated with hip fractures in older adults with impaired kidney function.

Design: Prospective population-based study.

Setting: Community-dwelling old population in Reykjavik, Iceland.

Subjects: A total of 875 older adults (mean baseline age 76 years) from the Age, Gene/Environment Susceptibility (AGES)-Reykjavik Study with impaired kidney function.

Methods: Quadriceps CSA and density were determined using computed tomography (CT), knee extension strength was measured with an isometric dynamometer chair, and muscular function was assessed using the Timed Up and Go (TUG) test. All muscle-related measurements were assessed twice over a mean follow-up of 5.2 years. Data on hip fracture incidence was obtained from medical records during a maximum of 8.4 years of follow-up time.

Results: Fully adjusted cox-proportional hazard regression models showed that a faster decline in quadriceps CSA and TUG test performance were significantly associated with increased hip fracture risk (HR = 1.55, 95% CI = 1.02-2.36, and HR = 1.80, 95% CI = 1.19-2.72, respectively). A faster decrease in quadriceps density and isometric knee extension strength were not associated with fracture risk.

Conclusions: Accelerated decline in CT-derived quadriceps CSA and muscular function, as measured by the TUG test's performance, are predictive of hip fracture risk in older adults with impaired kidney function. TUG test is a simple measure and easily included in routine medical examinations, compared to CT scans, which seems to be useful for identifying a subgroup of individuals with high risk of fracture.
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http://dx.doi.org/10.1016/j.exger.2021.111314DOI Listing
July 2021

Computed tomography-based skeletal muscle and adipose tissue attenuation: Variations by age, sex, and muscle.

Exp Gerontol 2021 07 10;149:111306. Epub 2021 Mar 10.

Laboratory of Epidemiology and Population Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Bethesda, MD, USA.

Objective: This study aimed to investigate how skeletal muscle attenuation and adipose tissue (AT) attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle vary according to the targeted muscles, sex, and age.

Design: Population-based cross-sectional study.

Setting: Community-dwelling old population in Reykjavik, Iceland.

Subjects: A total of 5331 older adults (42.8% women), aged 66-96 years from the Age, Gene/Environment Susceptibility (AGES)- Reykjavik Study, who participated in the baseline visit (between 2002 and 2006) and had valid thigh and abdominal computed tomography (CT) scans were studied.

Methods: Muscle attenuation and AT attenuation of the quadriceps, hamstrings, paraspinal muscle groups and the psoas muscle were determined using CT. Linear mixed model analysis of variance was performed for each sex, with skeletal muscle or AT attenuation as the dependent variable.

Results: Muscle attenuation decreased, and AT attenuation increased with age in both sexes, and these differences were specific for each muscle, although not in all age groups. Age-related differences in muscle and AT attenuation varied with specific muscle. In general, for both sexes, skeletal muscle attenuation of the hamstrings declined more than average with age. Men and women displayed a different pattern in the age differences in AT attenuation for each muscle.

Conclusions: Our data support the hypotheses that skeletal muscle attenuation decreases, and AT attenuation increases with aging. In addition, our data add new evidence, supporting that age-related differences in skeletal muscle and AT attenuation vary between muscles.
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http://dx.doi.org/10.1016/j.exger.2021.111306DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8096682PMC
July 2021

High incidence of fractures after R-CHOP-like chemotherapy for aggressive B-cell non-Hodgkin lymphomas.

Support Care Cancer 2021 Sep 10;29(9):5399-5408. Epub 2021 Mar 10.

Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, San Francisco, CA, USA.

Purpose: Patients with non-Hodgkin lymphoma (NHL) have a median age of 67, with 70% surviving over 5 years. Chemotherapy for aggressive NHL includes cyclophosphamide, anthracycline, and high doses of corticosteroids, which can impair bone health. By reviewing clinical characteristics and standard-of-care CT scans, we evaluate the prevalence and incidence of fractures and the clinical correlates of fractures in patients treated for aggressive B-cell NHL.

Methods: We retrospectively reviewed patients seen at the University of California San Francisco lymphoma clinic from January 1, 2016, to March 31, 2017 who had (1) aggressive B-cell NHL, (2) received first-line therapy with R-CHOP-like regimens, and had (3) CT scans pre- and post-treatment available for review. Associations between clinical variables and vertebral, rib, and pelvic fracture outcomes were assessed, and multivariate logistic regression models were used to identify predictors of prevalent and incident fractures.

Results: We identified 162 patients who met the inclusion criteria. Median age at diagnosis was 60 years. Of the 162 patients, 38 patients (28%) had prevalent fractures prior to receiving chemotherapy. Within 1 year after treatment, 16 patients (10%) developed new fractures. Having a prevalent fracture strongly predicted developing a new fracture after treatment, with incident fractures occurring in 12 of 38 patients with prevalent fractures versus 4 of 124 without prevalent fractures (odds ratio 10.45, p<0.0005).

Conclusion: Our results suggest that patients with aggressive B-cell NHL who receive R-CHOP-like therapy should be screened for fractures prior to treatment and those with existing fractures should be considered for therapy to decrease risk of new fractures.
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http://dx.doi.org/10.1007/s00520-021-06120-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8295123PMC
September 2021

Losartan Improves Memory, Neurogenesis and Cell Motility in Transgenic Alzheimer's Mice.

Pharmaceuticals (Basel) 2021 Feb 20;14(2). Epub 2021 Feb 20.

Department of Clinical Pharmacology, University Hospital of Tuebingen, 72076 Tuebingen, Germany.

Angiotensin receptor blockers (ARBs) have demonstrated multiple neuroprotective benefits in Alzheimer's disease (AD) models. However, their beneficial effects on memory deficits, cholinergic activity, neurogenesis and Amyloid beta (Aβ) clearance reveal significant interstudy variability. The delivery route can impact not only delivery but also targeting and therapeutic efficacy of ARBs. Our previous findings on the beneficial effects of intranasally delivered losartan in the APP/PS1 model of AD prompted us to explore the influence of the delivery route by employing here the systemic administration of losartan. Consistent with our previous results with intranasal losartan, repeated intraperitoneal administration (10 mg/kg) resulted in a remarkable decrease in Aβ plaques and soluble Aβ42, as well as inflammatory cytokines (IL-2, IL-6 and TNFα). The Aβ reduction can be ascribed to its facilitated degradation by neprilysin and diminished generation by BACE1. Losartan increased neurogenesis in vivo and in vitro and improved migratory properties of astrocytes isolated from adult transgenic AD mice. In summary, this data together with our previous results suggest therapeutic features of losartan which are independent of delivery route. The improvement of cell motility of Aβ-affected astrocytes by losartan deserves further investigation, which may lead to new strategies for AD treatment.
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http://dx.doi.org/10.3390/ph14020166DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7923419PMC
February 2021

Therapygenetic effects of 5-HTTLPR on cognitive-behavioral therapy in anxiety disorders: A meta-analysis.

Eur Neuropsychopharmacol 2021 Mar 20;44:105-120. Epub 2021 Jan 20.

Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University Hospital Frankfurt, Frankfurt am Main, Germany; Center of Mental Health, Department of Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Würzburg, Germany.

There is a recurring debate on the role of the serotonin transporter gene linked polymorphic region (5-HTTLPR) in the moderation of response to cognitive behavioral therapy (CBT) in anxiety disorders. Results, however, are still inconclusive. We here aim to perform a meta-analysis on the role of 5-HTTLPR in the moderation of CBT outcome in anxiety disorders. We investigated both categorical (symptom reduction of at least 50%) and dimensional outcomes from baseline to post-treatment and follow-up. Original data were obtained from ten independent samples (including three unpublished samples) with a total of 2,195 patients with primary anxiety disorder. No significant effects of 5-HTTLPR genotype on categorical or dimensional outcomes at post and follow-up were detected. We conclude that current evidence does not support the hypothesis of 5-HTTLPR as a moderator of treatment outcome for CBT in anxiety disorders. Future research should address whether other factors such as long-term changes or epigenetic processes may explain further variance in these complex gene-environment interactions and molecular-genetic pathways that may confer behavioral change following psychotherapy.
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http://dx.doi.org/10.1016/j.euroneuro.2021.01.004DOI Listing
March 2021

Acute aquatic toxicity of arsenic-based chemical warfare agents to Daphnia magna.

Aquat Toxicol 2021 Jan 25;230:105693. Epub 2020 Nov 25.

Institute of Oceanology, Polish Academy of Sciences, Sopot, Poland. Electronic address:

Sea dumping of chemical warfare (CW) took place worldwide during the 20th century. Submerged CW included metal bombs and casings that have been exposed for 50-100 years of corrosion and are now known to be leaking. Therefore, the arsenic-based chemical warfare agents (CWAs), pose a potential threat to the marine ecosystems. The aim of this research was to support a need for real-data measurements for accurate risk assessments and categorization of threats originating from submerged CWAs. This has been achieved by providing a broad insight into arsenic-based CWAs acute toxicity in aquatic ecosystems. Standard tests were performed to provide a solid foundation for acute aquatic toxicity threshold estimations of CWA: Lewisite, Adamsite, Clark I, phenyldichloroarsine (PDCA), CWA-related compounds: TPA, arsenic trichloride and four arsenic-based CWA degradation products. Despite their low solubility, during the 48 h exposure, all CWA caused highly negative effects on Daphnia magna. PDCA was very toxic with 48 h D. magna LC50 at 0.36 μg × L and Lewisite with EC50 at 3.2 μg × L. Concentrations at which no immobilization effects were observed were slightly above the analytical Limits of Detection (LOD) and Quantification (LOQ). More water-soluble CWA degradation products showed no effects at concentrations up to 100 mg × L.
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http://dx.doi.org/10.1016/j.aquatox.2020.105693DOI Listing
January 2021

Detection of chemical warfare agent related phenylarsenic compounds and multibiomarker responses in cod (Gadus morhua) from munition dumpsites.

Mar Environ Res 2020 Dec 23;162:105160. Epub 2020 Sep 23.

Finnish Institute for Verification of the Chemical Weapons Convention (VERIFIN), Department of Chemistry, University of Helsinki, A.I. Virtasen Aukio 1, FI-00014, University of Helsinki, Finland.

Recently, sea-dumped chemical weapons (CWs) containing toxic chemical warfare agents (CWAs) have raised international attention. It is well known that CWAs are leaking from corroded munitions causing a risk to the surrounding marine environment, while the impact on marine biota is still unknown. In this study, cod (Gadus morhua) was used as a model species to study the possible bioaccumulation of phenylarsenic CWAs and their negative effects at multiple levels of biological organization on fish living in the vicinity of a major CWs dumpsite in the Bornholm Basin in the Baltic Sea. In total, 14% of the cod muscle samples collected close to the main dumpsite contained trace levels of phenylarsenic CWAs. However, most of the biomarkers measured did not show clear differences between this area compared with a lesser contaminated reference area. On the other hand, significant changes in some biomarkers were observed in individuals containing trace levels of CWA-related chemicals. The results gained in this study have significant importance for environmental risk assessment and for evaluating the risk of CWA contamination for human seafood consumers.
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http://dx.doi.org/10.1016/j.marenvres.2020.105160DOI Listing
December 2020

Interaction of heparin and protamine in presence of overdosage: in vitro study.

Asian Cardiovasc Thorac Ann 2021 Jan 27;29(1):5-9. Epub 2020 Aug 27.

Gerinnungsambulanz Südheide, Hohne, Germany.

Background: Heparin is used for anticoagulation during cardiopulmonary bypass. After weaning from bypass, protamine is administered to neutralize the effects of heparin and thus reestablish hemostasis. Rotational thrombelastometry has been shown to discriminate between heparin and other impairing effects on coagulation. We analyzed the interaction of heparin and protamine under different conditions of overdosage in an in-vitro trial.

Methods: Blood samples were taken from 17 healthy volunteers, separated, and spiked in vitro with heparin, protamine for heparin neutralization, an overdosage of protamine, and two dosages of re-heparinization to evaluate heparin effects under the condition of protamine overdosage. All samples were analyzed in a standard ROTEM rotational thromboelastometry device after intrinsic activation with and without addition of heparinase. Coagulation time, maximum clot firmness, and clot formation time were recorded.

Results: Heparin led to prolongation of coagulation and clot formation times in the test without heparinase. Adequate protamine addition normalized the test, and overdosage of protamine led to significant prolongation of both times. Addition of heparin in the presence of protamine overdosage normalized these parameters.

Conclusion: We reconfirmed that the ROTEM device enables discrimination of the effects heparin and protamine on coagulation and detection of the coagulation-impairing effects of protamine overdosage. Furthermore, we were able to show a positive effect on coagulation times by heparin in the presence of protamine overdosage. Because this was an in-vitro study, these findings need to be confirmed in vivo, requiring further research.
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http://dx.doi.org/10.1177/0218492320955065DOI Listing
January 2021

Who knew? The misleading specificity of "double-blind" and what to do about it.

Trials 2020 Aug 5;21(1):697. Epub 2020 Aug 5.

Data for Solutions, Inc., Decatur, GA, USA.

Background: In randomized trials, the term "double-blind" (and its derivatives, single- and triple-blind, fully blind, and partially blind or masked) has no standard or widely accepted definition. Agreement about which groups are blinded is poor, and authors using these terms often do not identify which groups were blinded, despite specific reporting guidelines to the contrary. Nevertheless, many readers assume-incorrectly-that they know which groups are blinded. Thus, the term is ambiguous at best, misleading at worst, and, in either case, interferes with the accurate reporting, interpretation, and evaluation of randomized trials. The problems with the terms have been thoroughly documented in the literature, and many authors have recommended that they be abandoned.

Proposal: We and our co-signers suggest eliminating the use of adjectives that modify "blinding" in randomized trials; a trial would be described as either blinded or unblinded. We also propose that authors report in a standard table which groups or individuals were blinded, what they were blinded to, how blinding was implemented, and whether blinding was maintained. Individuals with dual responsibilities, such as caregiving and data collecting, would also be identified. If blinding was compromised, authors should describe the potential implications of the loss of blinding on interpreting the results.

Conclusion: "Double blind" and its derivatives are terms with little to recommend their continued use. Eliminating the use of adjectives that impart a false specificity to the term would reduce misinterpretations, and recommending that authors report who was blinded to what and how in a standard table would require them to be specific about which groups and individuals were blinded.
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http://dx.doi.org/10.1186/s13063-020-04607-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7409478PMC
August 2020

The modulating impact of cigarette smoking on brain structure in panic disorder: a voxel-based morphometry study.

Soc Cogn Affect Neurosci 2020 10;15(8):849-859

Department of Psychology, Humboldt-Universität zu Berlin, Berlin 10117, Germany.

Cigarette smoking increases the likelihood of developing anxiety disorders, among them panic disorder (PD). While brain structures altered by smoking partly overlap with morphological changes identified in PD, the modulating impact of smoking as a potential confounder on structural alterations in PD has not yet been addressed. In total, 143 PD patients (71 smokers) and 178 healthy controls (62 smokers) participated in a multicenter magnetic resonance imaging (MRI) study. T1-weighted images were used to examine brain structural alterations using voxel-based morphometry in a priori defined regions of the defensive system network. PD was associated with gray matter volume reductions in the amygdala and hippocampus. This difference was driven by non-smokers and absent in smoking subjects. Bilateral amygdala volumes were reduced with increasing health burden (neither PD nor smoking > either PD or smoking > both PD and smoking). As smoking can narrow or diminish commonly observed structural abnormalities in PD, the effect of smoking should be considered in MRI studies focusing on patients with pathological forms of fear and anxiety. Future studies are needed to determine if smoking may increase the risk for subsequent psychopathology via brain functional or structural alterations.
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http://dx.doi.org/10.1093/scan/nsaa103DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7543937PMC
October 2020

An investigation of genetic variability of DNA methyltransferases DNMT3A and 3B does not provide evidence for a major role in the pathogenesis of panic disorder and dimensional anxiety phenotypes.

J Neural Transm (Vienna) 2020 11 29;127(11):1527-1537. Epub 2020 May 29.

Department of Psychiatry, Psychosomatics and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, Margarete-Höppel Platz 1, 97080, Würzburg, Germany.

While DNA methylation patterns have been studied for a role in the pathogenesis of anxiety disorders, the role of the enzymes establishing DNA methylation-DNA methyltransferases (DNMTs)-has yet to be investigated. In an effort to investigate DNMT genotype-specific effects on dimensional anxiety traits in addition to the categorical phenotype of panic disorder, 506 panic disorder patients and 3112 healthy participants were assessed for anxiety related cognition [Agoraphobic Cognitions Questionnaire (ACQ)], anxiety sensitivity [Anxiety Sensitivity Index (ASI)] as well as pathological worry [Penn State Worry Questionnaire (PSWQ)] and genotyped for five single nucleotide polymorphisms (SNPs) in the DNMT3A (rs11683424, rs1465764, rs1465825) and DNMT3B (rs2424932, rs4911259) genes, which have previously been found associated with clinical and trait-related phenotypes. There was no association with the categorical phenotype panic disorder. However, a significant association was discerned between DNMT3A rs1465764 and PSWQ scores in healthy participants, with the minor allele conveying a protective effect. In addition, a marginally significant association between questionnaire scores (PSWQ, ASI) in healthy participants and DNMT3B rs2424932 was detected, again with the minor allele conveying a protective effect. The present results suggest a possible minor role of DNMT3A and DNMT3B gene variation in conveying resilience towards anxiety disorders. As the observed associations indicated a protective effect of two SNPs particularly with pathological worry, future studies are proposed to explore these variants in generalized anxiety disorder rather than panic disorder.
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http://dx.doi.org/10.1007/s00702-020-02206-xDOI Listing
November 2020

Successful containment of Covid-19 outbreak in a large maternity and perinatal center while continuing clinical service.

Pediatr Allergy Immunol 2020 07 17;31(5):560-564. Epub 2020 May 17.

Institute of Laboratory Medicine, Microbiology and Hygiene, Hospital of the Order of St. John, Regensburg, Germany.

With increasing number of SARS-CoV-2 infections and COVID-19 patients to be taken care of by the health system, more and more health workers become affected by the disease. It has been reported that right from the beginning of the outbreak in Lombardy up to 20% of the doctors and nurses became infected. Under these circumstances, the regular operation of health institutions already suffering from a shortage of staff becomes difficult. This has led to complete or partial shutdowns of hospitals, either due to a lack of uninfected personnel or because of uncontrollable chains of infection endangering patients. In one of the largest university perinatal center in Bavaria with more than 3000 births per year, an outbreak of COVID-19 occurred in March 2020, affecting 36 staff members, including doctors, nurses, and midwives. Here, we describe the outbreak and present the measures contributing to the successful containment of the outbreak within three weeks. At the same time, clinical services could be maintained, however, not without deployment of personnel exposed to employees infected with SARS-CoV-2. Apart from massive testing of personnel in pre-defined phases and increased hygiene measures, including a general obligation to wear surgical face masks, we identified the need to monitor cases of illness across all groups of employees, to ensure social distancing within personnel and to evaluate contacts of clinical personnel outside of the hospital environment, in order to be able to interpret chains of infections and to disrupt them. Overall, only a bundle of measures is needed to contain such an outbreak.
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http://dx.doi.org/10.1111/pai.13265DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264500PMC
July 2020

First evidence of explosives and their degradation products in dab (Limanda limanda L.) from a munition dumpsite in the Baltic Sea.

Mar Pollut Bull 2020 Jun 15;155:111131. Epub 2020 Apr 15.

Thünen Institute of Fisheries Ecology, Herwigstraße 31, 27572 Bremerhaven, Germany.

Corrosion and disintegration of munition shells from the World Wars increase the risk that explosives are released into the marine environment, exposing a variety of organisms. Only few studies investigated contamination of fish with explosives in the field under environmental conditions. Here we present a comprehensive study on the contamination status of dab (Limanda limanda) from a munition dumpsite and from reference sites in the Baltic Sea. Bile of 236 dab from four different study sites, including a dumpsite for conventional munitions, was investigated and explosive compounds were detected by high performance liquid chromatography-mass spectrometry. Five explosive compounds were identified, including 2,4,6-trinitrotoluene, 4-amino-2,6-dinitrolouene, and hexahydro-1,3,5-trinitro-1,3,5-triazine. 48% of the samples from the dumpsite contained at least one explosive compound. The results prove that toxic explosive compounds from a dumpsite in the Baltic Sea are accumulated by flatfish and may therefore pose a risk to fish health and human food safety.
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http://dx.doi.org/10.1016/j.marpolbul.2020.111131DOI Listing
June 2020

Influence of hunger on attentional engagement with and disengagement from pictorial food cues in women with a healthy weight.

Appetite 2020 08 29;151:104686. Epub 2020 Mar 29.

University of Groningen, Department of Clinical Psychology and Experimental Psychopathology, the Netherlands.

Because of inconsistencies in the field of attentional bias to food cues in eating behavior, this study aimed to re-examine the assumption that hungry healthy weight individuals have an attentional bias to food cues, but satiated healthy weight individuals do not. Since attentional engagement and attentional disengagement have been proposed to play a distinct role in behavior, we used a performance measure that is specifically designed to differentiate between these two attentional processes. Participants were healthy weight women who normally eat breakfast. In the satiated condition (n = 54), participants were instructed to have breakfast just before coming to the lab. In the fasted condition (n = 50), participants fasted on average 14 h before coming into the lab. Satiated women showed no stronger attentional engagement or attentional disengagement bias to food cues than to neutral cues. Fasted women did show stronger attentional engagement to food cues than to neutral cues that were shown briefly (100 ms). They showed no bias in attentional engagement to food cues that were shown longer (500 ms) or in attentional disengagement from food cues. These findings are in line with the assumption that healthy weight individuals show an attentional bias to food cues when food stimuli are motivationally salient. Furthermore, the findings point to the importance of differentiating between attentional engagement and attentional disengagement.
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http://dx.doi.org/10.1016/j.appet.2020.104686DOI Listing
August 2020

How thinking hurts: Rumination, worry, and avoidance processes in adjustment to bereavement.

Clin Psychol Psychother 2020 Jul 4;27(4):548-558. Epub 2020 Mar 4.

Department of Clinical Psychology, Faculty of Social Sciences, Utrecht University, Utrecht, The Netherlands.

Repetitive negative thought plays an important role in the maintenance of mental health problems following bereavement. To date, bereavement researchers have primarily focused on rumination (i.e., repetitive thought about negative events and/or negative emotions), yet the interest in worry (i.e., repetitive thought about uncertain future events) is increasing. Both cognitive processes potentially lead to poorer adaptation to bereavement by contributing to loss-related avoidance and behavioural avoidance of activities. The current study aims to establish the differential associations of rumination and worry with symptoms of depression and prolonged grief and clarify if avoidance processes mediate the associations of rumination and worry with symptom levels. Four hundred seventy-four recently bereaved adults (82% female) filled out questionnaires assessing rumination, worry, loss-related and behavioural avoidance, and depression and prolonged grief symptoms. Rumination and worry were both uniquely associated with depression and prolonged grief symptoms. Compared with worry, rumination related more strongly to prolonged grief symptoms, whereas correlations of both cognitive styles with depression symptoms did not differ. Loss-related avoidance and behavioural avoidance partially mediated the associations of rumination and worry with prolonged grief symptoms. Behavioural avoidance partially mediated the associations of rumination and worry with depression symptoms. Findings suggest that exposure and behavioural activation may be effective interventions to reduce repetitive thinking and psychopathology after bereavement.
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http://dx.doi.org/10.1002/cpp.2440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7497101PMC
July 2020

Antifibrotic Effects of Amyloid-Beta and Its Loss in Cirrhotic Liver.

Cells 2020 02 17;9(2). Epub 2020 Feb 17.

Department of Clinical Pharmacology, University Hospital of Tübingen, 72076 Tübingen, Germany.

The function and regulation of amyloid-beta (Aβ) in healthy and diseased liver remains unexplored. Because Aβ reduces the integrity of the blood-brain barrier we have examined its potential role in regulating the sinusoidal permeability of normal and cirrhotic liver. Aβ and key proteins that generate (beta-secretase 1 and presenilin-1) and degrade it (neprilysin and myelin basic protein) were decreased in human cirrhotic liver. In culture, activated hepatic stellate cells (HSC) internalized Aβ more efficiently than astrocytes and HSC degraded Aβ leading to suppressed expression of α-smooth muscle actin (α-SMA), collagen 1 and transforming growth factor β (TGFβ). Aβ also upregulated sinusoidal permeability marker endothelial NO synthase (eNOS) and decreased TGFβ in cultured human liver sinusoidal endothelial cells (hLSEC). Liver Aβ levels also correlate with the expression of eNOS in transgenic Alzheimer's disease mice and in human and rodent cirrhosis/fibrosis. These findings suggest a previously unexplored role of Aβ in the maintenance of liver sinusoidal permeability and in protection against cirrhosis/fibrosis via attenuation of HSC activation.
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http://dx.doi.org/10.3390/cells9020452DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7072823PMC
February 2020

Lack of Correlation of Mean Corpuscular Volume to White Blood Cell Ratio to Thiopurine Levels.

J Pediatr Gastroenterol Nutr 2020 05;70(5):e107-e110

GPGE-Educational Center for Pediatric Gastroenterology, Department of Pediatrics, Medical University of Graz, Graz, Austria.

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http://dx.doi.org/10.1097/MPG.0000000000002662DOI Listing
May 2020

Studying the metabolism of toxic chemical warfare agent-related phenylarsenic chemicals in vitro in cod liver.

J Hazard Mater 2020 06 3;391:122221. Epub 2020 Feb 3.

Finnish Institute for Verification of the Chemical Weapons Convention (VERIFIN), Department of Chemistry, University of Helsinki, P.O. Box 55, FI-00014 University of Helsinki, Finland.

Large quantities of chemical warfare agents (CWAs), such as phenylarsenic chemicals, were disposed by sea-dumping after World War II. Nowadays, the release of these toxic chemicals from munitions poses a potential threat to living organisms. This study investigates the fate of these chemicals in fish by exposing selected CWA-related phenylarsenic chemicals and their oxidation products to cod (Gadus morhua) liver S9 fraction in vitro. Clark I (DA), Adamsite (DM) and their corresponding oxidation products as well as triphenylarsine oxide (TPA[ox]) and phenylarsonic acid (PDCA[ox]) were used as chemicals in in vitro experiments. Glutathione (GSH) conjugates of DA, DM and PDCA-related chemicals were found to be the most dominant metabolites, and methylated metabolites were detected as well, suggesting that these compounds are metabolised in the presence of cod liver enzymes. TPA[ox] was the only compound tested that did not form a GSH conjugate or methylated metabolite, indicating a different biotransformation pathway for this compound. Furthermore, hydroxylated metabolites were detected for each tested chemical. Due to their reactive nature, GSH conjugates may be difficult to detect in fish samples from CWA dumpsites. In contrast, both methylated and hydroxylated metabolites of phenylarsenic chemicals are promising target chemicals for the detection of CWA-related contamination in fish.
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http://dx.doi.org/10.1016/j.jhazmat.2020.122221DOI Listing
June 2020

Effect of CBT on Biased Semantic Network in Panic Disorder: A Multicenter fMRI Study Using Semantic Priming.

Am J Psychiatry 2020 03 16;177(3):254-264. Epub 2019 Dec 16.

Department of Psychiatry and Psychotherapy and Marburg Center for Mind, Brain, and Behavior, Philipps-University Marburg, Marburg, Germany (Yang, Konrad, Straube, Kircher); Department of Psychiatry, Psychosomatics, and Psychotherapy, Center of Mental Health, University Hospital of Würzburg, University of Würzburg, Würzburg, Germany (Lueken, Herrmann, Deckert); Department of Psychology, Humboldt-Universität zu Berlin, Berlin, Germany (Lueken); Department of Biological and Clinical Psychology, University of Greifswald, Greifswald, Germany (Richter, Hamm); Department of Psychiatry and Psychotherapy, Campus Charité Mitte, Charité-Universitätsmedizin Berlin, Berlin, Germany (Wittmann, Ströhle); Department of Psychiatry, Agaplesion Diakonieklinikum Rotenburg (Wümme), Germany (Konrad); Department of Clinical Radiology, University of Münster, Münster, Germany (Pfleiderer); Christoph-Dornier-Foundation for Clinical Psychology, Bremen, Germany (Lang); Department of Psychiatry and Psychotherapy, University of Hamburg, Hamburg, Germany (Lang); Functional Imaging Unit, Institute for Diagnostic Radiology and Neuroradiology, University of Greifswald, Greifswald, Germany (Lotze); Department of Psychiatry, University of Münster, Münster, Germany (Arolt); and Institute of Clinical Psychology and Psychotherapy, Technische Universität Dresden, Dresden, Germany (Wittchen).

Objective: Cognitive-behavioral therapy (CBT) has been hypothesized to act by reducing the pathologically enhanced semantic, anxiety-related associations of patients with panic disorder. This study investigated the effects of CBT on the behavioral and neural correlates of the panic-related semantic network in patients with panic disorder.

Methods: An automatic semantic priming paradigm specifically tailored for panic disorder, in which panic symptoms (e.g., "dizziness") were primed by panic triggers (e.g., "elevator") compared with neutral words (e.g., "bottle"), was performed during functional MRI scanning with 118 patients with panic disorder (compared with 150 healthy control subjects) before and 42 patients (compared with 52 healthy control subjects) after an exposure-based CBT. Neural correlates were investigated by comparing 103 pairs of matched patients and control subjects at the baseline (for patients) or T1 (for control subjects) assessment and 39 pairs at the posttreatment or T2 assessment.

Results: At baseline or T1, patients rated panic-trigger/panic-symptom word pairs with higher relatedness and higher negative valence compared with healthy control subjects. Patients made faster lexical decisions to the panic-symptom words when they were preceded by panic-trigger words. This panic-priming effect in patients (compared with control subjects) was reflected in suppressed neural activation in the left and right temporal cortices and insulae and enhanced activation in the posterior and anterior cingulate cortices. After CBT, significant clinical improvements in the patient group were observed along with a reduction in relatedness and negative valence rating and attenuation of neural activation in the anterior cingulate cortex for processing of panic-trigger/panic-symptom word pairs.

Conclusions: The findings support a biased semantic network in panic disorder, which is normalized after CBT. Attenuation of anterior cingulate cortex activation for processing of panic-related associations provides a potential mechanism for future therapeutic interventions.
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http://dx.doi.org/10.1176/appi.ajp.2019.19020202DOI Listing
March 2020

A Critical Update of the Assessment and Acute Management of Patients with Severe Burns.

Adv Wound Care (New Rochelle) 2019 Dec 6;8(12):607-633. Epub 2019 Nov 6.

Sutton Laboratories, The Kolling Institute, St. Leonards, Australia.

Burns are debilitating, life threatening, and difficult to assess and manage. Recent advances in assessment and management have occurred since a comprehensive review of the care of patients with severe burns was last published, which may influence research and clinical practice. Recent advances have occurred in the understanding of burn pathophysiology, which has led to the identification of potential biomarkers of burn severity, such as protein C. There is new evidence about the potential superiority of natural colloids over crystalloids during fluid resuscitation, and new evidence about components of initial and perioperative management, including an improved understanding of pain following burns. The limitations of the clinical examination highlight the need for imaging and biomarkers to assist in estimations of burn severity. Fluid resuscitation reduces mortality, although there is conjecture over the ideal method. The subsequent perioperative period is associated with significant morbidity and the evidence for preventing and treating pain, infection, and fluid overload while maximizing wound healing potential is described. Promising developments are ongoing in imaging technology, histopathology, biomarkers, and wound healing adjuncts such as hyperbaric oxygen therapy, topical negative pressure therapy, stem cell treatments, and skin substitutes. The greatest benefit from further research on management of patients with burns would most likely be derived from the elucidation of optimal fluid resuscitation protocols, pain management protocols, and surgical techniques from randomized controlled trials.
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http://dx.doi.org/10.1089/wound.2019.0963DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6904939PMC
December 2019

Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study.

J Bone Miner Res 2020 04 30;35(4):681-690. Epub 2019 Dec 30.

Department of Physical Therapy, School of Health and Human Sciences, Indiana University, Indianapolis, IN, USA.

Physical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes, obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n = 16) and baseball pitchers (n = 16) were utilized as within-subject controlled models as they preferentially load their take-off leg and leg contralateral to their throwing arm, respectively. Controls (n = 15) were included but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences but less than pitchers. Pitchers had 5.8% (95% confidence interval [CI] 3.9%-7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95% CI 1.4%-6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball pitching induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (ie, fall onto the greater trochanter), raising questions as to how to better target these variables with PA. © 2019 American Society for Bone and Mineral Research.
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http://dx.doi.org/10.1002/jbmr.3939DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7145739PMC
April 2020
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