[Late-life depression and frailty-Epidemiological, clinical and neurobiological associations]. / Depression im Alter und Frailty ­ epidemiologische, klinische und neurobiologische Zusammenhänge.

BACKGROUND: Depression is the most common mental disorder in older adults and is influenced by age-related processes. Frailty is a well-established clinical expression of ageing that implies a state of increased vulnerability to stressor events as well as increased risks of disability, hospitalization and death. Neurobiological findings will disentangle the comorbidity of frailty and depression and may inform future management of depression in old age. OBJECTIVE: This narrative review provides an overview of the comorbidity of late-life depression and frailty, with a focus on neuroscientific findings that are organized within the research domain criteria (RDoC) framework. RESULTS: More than one third of old people with depression are affected by frailty, which results in more chronic depression and in poorer efficacy and tolerability of antidepressant medication. Depression and frailty share motivational and psychomotor characteristics, particularly apathy, decreased physical activity and fatigue. In patients with frailty, altered activity of the supplementary motor cortex is associated with motor performance deficits. Patients with late-life depression and apathy are characterized by abnormal structure and altered functional connectivity of the reward network and the salience network, along with altered functional connectivity of these networks with premotor brain areas. CONCLUSION: Identifying frailty in older adults with depression is relevant for prognostic assessment and treatment. A better understanding of the neuronal mechanisms of comorbidity will provide potential targets for future personalized therapeutic interventions.

Increases in Future AR Count and Size: Overview of the ARTMIP Tier 2 CMIP5/6 Experiment.

The Atmospheric River (AR) Tracking Method Intercomparison Project (ARTMIP) is a community effort to systematically assess how the uncertainties from AR detectors (ARDTs) impact our scientific understanding of ARs. This study describes the ARTMIP Tier 2 experimental design and initial results using the Coupled Model Intercomparison Project (CMIP) Phases 5 and 6 multi-model ensembles. We show that AR statistics from a given ARDT in CMIP5/6 historical simulations compare remarkably well with the MERRA-2 reanalysis. In CMIP5/6 future simulations, most ARDTs project a global increase in AR frequency, counts, and sizes, especially along the western coastlines of the Pacific and Atlantic oceans. We find that the choice of ARDT is the dominant contributor to the uncertainty in projected AR frequency when compared with model choice. These results imply that new projects investigating future changes in ARs should explicitly consider ARDT uncertainty as a core part of the experimental design.

Treatment of children with hyperbaric oxygenation (HBOT): a Europe-wide survey.

BACKGROUND: Hyperbaric oxygenation therapy (HBOT) is used as emergency treatment for decompression sickness, gas embolism, carbon monoxide intoxication, and necrotizing fasciitis. There is low evidence and little clinical knowledge about the treatment of children with HBOT. METHODS: We sent an internet-based questionnaire to HBO centers in Europe to gain information about their experience with children and HBOT. RESULTS: Out of all HBO-centers who participated in the questionnaire 90% treat children analogue to adults about indication and HBOT protocol. Most treated children had life-threatening indications or the risk of organ loss. The reported rate of side effects was: 6.8% anxiety, 2.4% barotrauma, 0.9% seizure, 0.2% retinopathy and no case of pulmonary barotrauma or oxygen toxicity. CONCLUSIONS: HBO therapy for children is present in European HBO centers. The rate of severe side effects is as low to the rates in adults; apart from this, oxygen-related seizures and anxiety are more frequent. A special focus seems necessary on the psychological management of the children, because anxiety is common depending on the age of the children. Especially for smaller children, an adequate psychological support seems essential. Prospective observational or controlled studies in children seem necessary to create relevant clinical evidence for HBOT and to observe the rate of side-effects.

Comparison of the culture method with multiplex PCR for the confirmation of Legionella spp. and Legionella pneumophila.

AIMS: The detection and enumeration of Legionella spp. in water samples are typically performed via a cultural technique standardized in ISO 11731. This method is time-consuming (up to 15 days), and the specificity of the confirmation step is questionable. This study proposes the use of multiplex polymerase chain reaction (PCR) to confirm presumptive Legionella colonies directly from the culture plate; this shortens the response time by 2-5 days while still reporting results in colony forming units (CFU). METHODS AND RESULTS: Two laboratories analysed a total of 290 colonies to compare the confirmation step of Legionella spp. and Legionella pneumophila in accordance with ISO 11731 by culture growth and agglutination vs multiplex PCR. Discordant results were resolved by the swiss national reference laboratory. The data were evaluated following ISO 16140 and showed that the PCR-technique had higher specificity. CONCLUSIONS: The confirmation of Legionella spp., L. pneumophila and L. pneumophila serogroup 1 by multiplex PCR allows detection of positive colonies more rapidly and with higher specificity. SIGNIFICANCE AND IMPACT OF THE STUDY: The study highlights a possibility to shorten the response time significantly during the enumeration of Legionella spp. and achieving a higher specificity while adhering to the legally recognized reporting in CFU.

Atmospheric blocking and intercomparison of objective detection methods: flow field characteristics.

Objective methods for identifying and quantifying atmospheric blocking have been developed over recent decades, primarily targeting North Atlantic blocks. Differences arise from these methods, leading to changes in the resultant blocking climatology. To understand these differences, and better inform future assessments built on quantitative detection of blocks, this paper examines blocking properties produced by three different objective detection algorithms over the global extratropics. Blocking criteria examined include 500 hPa geopotential height anomaly ( Z ∗ ), column-averaged potential vorticity anomaly ( P V ∗ ), and 500 hPa geopotential height gradient (AGP). Results are analyzed for blocking climatologies and for instantaneous blocking patterns, as well as distributions of block size, speed, duration, and distance traveled. The results emphasize physical characteristics of the flow field and the subsequent blocking regions that emerge; overall, P V ∗ and Z ∗ blocked regions often have higher pattern correlation and spatial similarity, though these two methods also display high agreement with AGP in some instances. Z ∗ finds the largest (and greatest number of) blocked regions, while P V ∗ -detected regions are smallest in all instances except Southern Hemisphere winter. In some cases, P V ∗ tracks a nearby jet streak, leading to differences with height-based algorithms. All three algorithms detect some questionable low-latitude blocks that are stationary and persist but do not impair zonal flow, although at different times. Therefore, careful consideration of the algorithm biases is important in future blocking studies. For example, linking extreme weather to detected blocking could vary substantially depending on the algorithm used.

Whole blood miRNA expression analysis reveals miR-3613-3p as a potential biomarker for dedifferentiated liposarcoma.

BACKGROUND: Liposarcoma constitute about 13% of all soft tissue sarcoma and are associated with a high risk of metastases. As the preoperative differentiation between benign and malign lipomatous tumors is restricted to magnetic resonance imaging, computed tomography and biopsy, we performed a miRNA array to distinguish dedifferentiated liposarcoma patients from healthy controls and lipoma patients. METHODS: Blood samples of patients with dedifferentiated liposarcoma, healthy controls and lipoma patients were collected. Whole blood RNA was extracted and samples of patients with dedifferentiated liposarcoma (n= 6) and of healthy donors (n= 4) were analyzed using an Affymetrix GeneChip miRNA Array v. 4.0. qRT-PCR was carried out to confirm the most differentially expressed miRNA; being further analyzed in an independent cohort of healthy controls as well as in lipoma patients. RESULTS: As shown by the microarray, two miRNAs (miR-3613-3p, miR-4668-5p) were shown to be significantly upregulated (fold change: > 2.5; p< 0.05) in patients with dedifferentiated liposarcoma (n= 6) as compared to healthy controls (n= 4). miR-3613-3p was further validated by qRT-PCR to be significantly upregulated in dedifferentiated liposarcoma patients compared to an independent cohort of healthy controls (n= 3) and lipoma patients (n= 5). CONCLUSION: We identified a specific whole blood miRNA (miR-3613-3p) that may serve to distinguish between dedifferentiated liposarcoma patients and healthy controls, thus potentially serving as a specific biomarker for dedifferentiated liposarcoma.

California's Drought of the Future: A Midcentury Recreation of the Exceptional Conditions of 2012-2017.

The California drought of 2012-2016 was a record-breaking event with extensive social, political, and economic repercussions. The impacts were widespread and exposed the difficulty in preparing for the effects of prolonged dry conditions. Although the lessons from this drought drove important changes to state law and policy, there is little doubt that climate change will only exacerbate future droughts. To understand the character of future drought, this paper examines this recent drought period retrospectively and prospectively, that is, as it occurred historically and if similar dynamical conditions to the historical period were to arise 30 years later (2042-2046) subject to the effects of climate change. Simulations were conducted using the Weather Research and Forecasting model using the pseudo global warming method. The simulated historical and future droughts are contrasted in terms of temperature, precipitation, snowpack, soil moisture, evapotranspiration, and forest health. Overall, the midcentury drought is observed to be significantly worse, with many more extreme heat days, record-low snowpack, increased soil drying, and record-high forest mortality. With these findings in mind, the data sets developed in this study provide a means to structure future drought planning around a drought scenario that is realistic and modeled after a memorable historical analog.

Levels of activated platelet-derived microvesicles in patients with soft tissue sarcoma correlate with an increased risk of venous thromboembolism.

BACKGROUND: Microvesicles are small vesicles expressing specific antigens from their cells of origin. Elevated levels of microvesicles have been shown to be associated with coagulation disorders as well as with different types of malignancies. This study aims to evaluate a possible correlation of different microvesicle subpopulations with a positive history of venous thromboembolism (VTE) in patients with soft tissue sarcoma. METHODS: Annexin V - positive microvesicles, leukocyte (CD45-positive), platelet (CD61-positive), activated platelet (CD62P-, CD63-positive), endothelium-derived (CD62E-positive) and tissue-factor (CD142-positive) microvesicles were identified in the peripheral blood of patients with soft tissue sarcoma (n = 39) and healthy controls (n = 17) using fluorescence-activated cell sorting (FACS). RESULTS: Both the total amount of Annexin V-positive microvesicles and levels of endothelium-derived (CD62E-positive) microvesicles were shown to decrease significantly after tumor resection (n = 18, p = 0.0395 and p = 0.0109, respectively). Furthermore, the total amount of Annexin V - positive microvesicles as well as leukocyte (CD45-positive) and endothelium-derived (CD62E-positive) microvesicles were significantly higher in patients with grade 3 (G3) soft tissue sarcoma (n = 9) compared to healthy controls (n = 17) (p = 0.0304, p = 0.0254 and p = 0.0357, respectively). Moreover, patients with G3 soft tissue sarcoma (n = 9) presented higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles compared to patients with grade 2 (G2) soft tissue sarcoma (n = 8) (p = 0.0483 and p = 0.0045). Patients with grade 1 (G1) soft tissue sarcoma (n = 3) presented with significantly lower levels of platelet (CD61-positive) microvesicles than patients with G3 soft tissue sarcoma (n = 9) (p = 0.0150). In patients with a positive history of VTE (n = 11), significantly higher levels of activated platelet (CD62P- and CD63-positive) microvesicles (p = 0.0078 and p = 0.0450, respectively) were found compared to patients without a history of VTE (n = 28). CONCLUSION: We found significantly higher levels of Annexin V-positive and endothelium-derived (CD62E-positive) microvesicles to be circulating in the peripheral blood of patients with G3 soft tissue sarcoma compared to patients with G2 soft tissue sarcoma. Furthermore, we showed that high counts of activated platelet-derived microvesicles correlate with the occurrence of VTE. Thus, the detection of these microvesicles might be an interesting new tool for early diagnosis of soft tissue sarcoma patients with increased risk for VTE, possibly facilitating VTE prevention by earlier use of thromboprophylaxis.

Synovial Sarcoma Microvesicles Harbor the SYT-SSX Fusion Gene Transcript: Comparison of Different Methods of Detection and Implications in Biomarker Research.

Background. Synovial sarcoma is an aggressive soft-tissue malignancy. This study examines the presence of the SYT-SSX fusion transcript in synovial sarcoma microvesicles as well as its potential role as a biomarker for synovial sarcoma. Patients and Methods. Microvesicle release of synovial sarcoma cells was examined by transmission electron microscopy. RNA-content was analyzed by qPCR, nested PCR, nested qPCR, and droplet digital PCR to compare their sensitivity for detection of the SYT-SSX fusion gene transcript. Whole blood RNA, RNA of mononuclear cells, and microvesicle RNA of synovial sarcoma patients were analyzed for the presence of the fusion gene transcripts. Results. Electron microscopic analysis revealed synovial sarcoma cells releasing membrane-enclosed microvesicles. In vitro, the SYT-SSX fusion gene transcript was detected in both synovial sarcoma cells and microvesicles. Nested qPCR proved to be the most sensitive in detecting the SYT-SSX fusion gene mRNA. In contrast, the fusion gene transcript was not detected in peripheral blood cells and microvesicles of synovial sarcoma patients. Conclusion. Synovial sarcoma cells release microvesicles harboring the SYT-SSX fusion transcript. Nested qPCR proved to be the most sensitive in detecting the SYT-SSX fusion gene mRNA; however, more sensitive assays are needed to detect cancer-specific microvesicles in the peripheral blood of cancer patients.

Implementation of Safe Patient Handling in the U.S. Veterans Health System: A Qualitative Study of Internal Facilitators' Perceptions.

BACKGROUND: Although the literature has noted the positive effects of facilitation in implementation research, little is known about what facilitators do or how they increase adoption of a program. The purpose of this study was to understand internal facilitation activities in implementing a national safe patient handling program from the perspective of facility coordinators who implemented the program. METHODS: Using a qualitative descriptive design, data were collected in five focus groups at two international Safe Patient Handling and Mobility Conferences. Participants were 38 facility coordinators implementing a safe patient handling program in the Department of Veterans Affairs medical centers throughout the United States. Data were analyzed using direct content analysis to gather descriptions of internal facilitation. RESULTS: The internal facilitation process involved engaging multiple disciplines and levels of leadership for implementation. Fifty-four facilitation activities were identified, including five activities not currently listed in an existing taxonomy. Key characteristics and skills of facilitators included persistence, credibility and clinical experience, and leadership and project management experience. Themes were mapped onto an existing framework and taxonomy of facilitation activities. LINKING EVIDENCE TO ACTION: Internal facilitation is both an implementation intervention and a process involving a wide range of activities. The findings provide an understanding of what internal facilitators are doing to support practice changes and the characteristics and skills of internal facilitators that are likely to result in long-term organizational change. Five recommendations for action address organizations, senior leaders, and internal facilitators.

[Psycho-oncology for speech therapists: establishment and conception of the course PSYKOL]. / Psychoonkologie für Logopäden und Sprechwissenschaftler : Begründung und Konzeption des Kurses PSYKOL.

OBJECTIVE: Head and neck cancer patients show a high psychiatric comorbidity, yet receive only little psychosocial support. Therefore, a specific psychosocial qualification for speech therapists working with head and neck cancer patients seems necessary. MATERIAL AND METHODS: A course was developed based on a process model. Questionnaires were completed by speech therapists (self-evaluation of working situation; n = 15) as well as therapists interested in further training (collection of issues in the work with head and neck patients who are under psychological pressure assessed as problematic by the therapists; n = 27), whose competence in communication was also evaluated. In addition, a literature research was conducted and a focus group was formed. RESULTS: High psychosocial demands within the therapists' work with tumor patients and difficulties in communication became obvious. Nearly all interviewees frequently used nonconducive communication patterns, yet implicit knowledge existed (usage of a favorable conversational style in multiple choice test: 68 %). The content and concept of the curriculum were discussed within the focus group and led to the final version of the training. CONCLUSION: A customised psycho-social training curriculum for speech therapists has been developed.

Pain intensity, pain interference and characteristics of spinal cord injury.

STUDY DESIGN: Postal survey. OBJECTIVES: To examine if the intensity of pain in persons with spinal cord injury (SCI) varied as a function of pain site, and to identify the patient and SCI characteristics associated with pain location, pain intensity and pain interference in a sample of persons with SCI. SETTING: Community sample, United States. METHODS: A postal survey including measures of pain intensity, pain interference, other pain, demographic and medical characteristics was completed by 238 adults with SCI. RESULTS: Average pain intensity was moderate and pain was common across the body. Demographic and medical variables, including SCI level, were generally not associated with pain prevalence, intensity and interference. However, persons with higher level injuries were more likely to report upper extremity pain than persons with paraplegic injuries. The lower body was the location of the highest pain ratings. CONCLUSION: Persons with SCI tend to experience high pain intensity over multiple body locations. Lower body pain was as common as upper extremity pain, but tended to be more intense.

Virtual planning of multicatheter brachytherapy implants for accelerated partial breast irradiation.

Over the last decade, increasing numbers of breast cancer patients are being treated using interstitial radioactive implants (brachytherapy). Multiple catheters are placed in the breast using a free-hand or template-guided approach. The configuration of the catheters and their relation to the tumor target volume are crucial to effective treatment. Catheter insertion requires a high level of experience to produce an implant of excellent quality. Construction of optimal catheter configuration prior to the procedure (virtual planning) would reduce the dependence of implant quality on the skill of the physician. Currently available commercial planning systems do not allow for virtual planning. We have developed software which inputs the target anatomy for a prospective patient and matches it to a previously-delivered catheter configuration from an institutional implant library. The archived catheter arrangement is then customized to fit the new target volume. The user can actually explore the implications of variations in catheter number and spatial arrangement. This may significantly improve the quality of implants that would otherwise be designed strictly based on a physician's prior experience. In an academic environment, this new resource could lead to better, faster results in the treatment of breast cancer.

[Treatment of Acute Central Retinal Artery Occlusion (CRAO) by Hyperbaric Oxygenation Therapy (HBO)--Pilot study with 21 patients]. / Behandlung akuter retinaler Zentralarterienverschlüsse (ZAV) mit der hyperbaren Sauerstofftherapie (HBO)--Pilotstudie an 21 Patienten.

BACKGROUND: Central retinal artery occlusion causes severe loss of vision. Treatment trials include massage of the globe, paracentesis, antiglaucomatous eye drops, haemodilution or lysis therapy, which in individual cases did improve the visual outcome, although in general the prognosis remains poor. In this study we applied hyperbaric oxygenation treatment additionally to haemodilution to overcome retinal ischaemia until spontaneous recanalisation of the central retinal artery occurs. PATIENTS AND METHODS: Patients with central retinal artery occlusion and onset of symptoms up to 12 h were included. Following initial ocular massage and application of antiglaucomatous eyedrops, hyperbaric oxygenation treatment was performed twice daily for up to three days. RESULTS: 21 patients could be included. The time lag between onset of symptoms and admission was between 4 and 12 h. Initial visual acuity ranged from light perception to 0.08. On discharge 19 patients reported on a subjective visual improvement which could be confirmed in 13 patients. In 9 patients an initial increase of visual acuity under hyperbaric oxygenation treatment could be observed which however was again reduced by at least one line on discharge. No patient experienced vision loss below admission vision. CONCLUSIONS: Hyperbaric oxygenation treatment seems to improve the visual outcome in central retinal artery occlusion. Major parameters for visual prognosis are the time lag from the onset of symptoms to the beginning of hyperbaric oxygenation treatment and the time lag until retinal reperfusion begins. Hyperbaric oxygenation treatment can compensate retinal ischaemia; however, the lack of glucose and accumulation of toxic metabolites is not addressed. A combination of hyperbaric oxygenation treatment with administration of glutamate antagonists or intravitreal glucose application might further improve the visual outcome.

Arthroscopic arthrodesis of the ankle joint.

SUMMARY: The authors report on 15 cases of arthrodesis of the ankle joint performed by operative arthroscopy. The follow-up ranges from 1 to 3 years, and 100% of the ankle joints achieved fusion at an average of 11.5 weeks. Two of the patients had some hindfoot pain, probably because of degenerative changes to their subtalar joints, even with this short follow-up. Five patients required further surgical treatment to correct complications related to infection, symptomatic hardware, or subtalar joint arthritis. Although the fusion rate is certainly encouraging, this procedure in the senior author's hand has a significant complication rate.

Social and functional variables associated with urinary tract infections in persons with spinal cord injury.

OBJECTIVE: Urinary tract infections (UTIs) and their complications remain a major source of morbidity and mortality after spinal cord injury (SCI). There has been much investigation into the physiological changes in persons with SCI and how these predispose to the development of UTIs, but other potentially influential variables are not so well understood. The purpose of this study is to examine behavioral, social, and functional factors and their relationship with UTIs. Our hypothesis is that lower UTI frequency will be associated with higher functional abilities, increased productivity, and higher life satisfaction scores. DESIGN: Respondents to a mailed questionnaire reported information on demographics, bladder management methods, functioning, productivity, and life satisfaction. PATIENTS: A volunteer sample from a list of all people with SCI previously treated at a university medical center rehabilitation medicine SCI inpatient service and/or outpatient SCI clinic from 1991 through 1994. RESULTS: There were 81 (35%) responses to 229 received mailings. Mean reported UTIs were 1.37 (SD = 2.66) per year and 4.77 (SD = 6.70) over a 3-year period. UTIs per year and total UTIs over 3 years were negatively associated with functioning and productivity (number of hours worked per week), but were not associated with life satisfaction scores. CONCLUSION: As a result of this study there is an improved understanding of social and functional variables and how these may correlate with UTI incidence in this population. Further research into these variables is warranted.

[Biological osteosyntheses]. / Biologische Osteosynthesen.

Soft tissue condition and local blood circulation are most important concerning bone reconstruction and healing of fractures. Therefore additional damage of soft tissue caused by operations must be avoided. Using biological osteosynthesis as much stability as necessary and highest possible saving of vascularity should be achieved. Most important and actual techniques will be discussed in this paper. Today's method of choice in long bone shaft fractures is the unreamed interlokked nail. On the contrary exact reposition and minimal fixation with screws and plates is the standard in fractures near the joint to gain exercise stability.

Results of hypotensive anesthesia in operative treatment of thoracolumbar fractures.

In a retrospective study of 109 patients who had Harrington instrumentation of thoracolumbar fractures, the results of normotensive anesthesia (75 patients) were compared with those of deliberate hypotensive anesthesia (34 patients). Estimated blood loss (EBL) and EBL per minute were significantly less (p less than 0.05) with hypotensive anesthesia. Neurological status of patients with incomplete or no deficits, monitored intraoperatively with either the Stagnara wake-up test (63 patients) or with somatosensory evoked potentials (23 patients), did not change during either the normotensive or hypotensive anesthesia. Deliberate hypotensive anesthesia is a safe and effective method for reducing blood loss during posttraumatic spinal stabilizations.