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Introduction: Older adults undergoing surgery are at risk of postoperative neurocognitive disorders, prompting the need for preoperative cognitive screening in this population. Traditionally, cognitive screening has been conducted in-person using brief assessment tools such as the Montreal Cognitive Assessment (MoCA) or the Mini-Mental State Examination (MMSE). More comprehensive test batteries, such as the Uniform Data Set (UDS) Neuropsychological Battery, and its remote testing version, the Uniform Data Set version 3 tele-adapted test battery (UDS v3.0 T-cog), have been developed to assess cognitive decline in normal aging and disease conditions, but have not been applied in the perioperative setting. Methods: We assessed the feasibility of using this remote UDS v3.0 T-cog battery for preoperative cognitive assessment in 81 older adults 65+ scheduled for lower extremity joint replacement surgery. Results: Our results indicate that the UDS v3.0 T-cog achieves 99% completion rates and demonstrates high patient satisfaction. Further, we found 28% of subjects were cognitively impaired in this patient cohort. Discussion: These findings suggest that the UDS v3.0 T-cog is a feasible tool for assessing cognitive function in the older adult perioperative population. To our knowledge, this is the first study to apply this comprehensive remote test battery in the preoperative setting. [ABSTRACT FROM AUTHOR]

Mammals in arid zones have to trade off thermal stress, predation pressure, and time spent foraging in a complex thermal landscape. We quantified the relationship between the environmental heat load and activity of a mammal community in the hot, arid Kalahari Desert. We deployed miniature black globe thermometers within the existing Snapshot Safari camera trap grid on Tswalu Kalahari Reserve, South Africa. Using the camera traps to record species' activity throughout the 24‐h cycle, we quantified changes in the activity patterns of mammal species in relation to heat loads in their local environment. We compared the heat load during which species were active between two sites with differing predator guilds, one where lion (Panthera leo) biomass dominated the carnivore guild and the other where lions were absent. In the presence of lion, prey species were generally active under significantly higher heat loads, especially during the hot and dry spring. We suggest that increased foraging under high heat loads highlights the need to meet nutritional requirements while avoiding nocturnal activity when predatory pressures are high. Such a trade‐off may become increasingly costly under the hotter and drier conditions predicted to become more prevalent as a result of climate change within the arid and semi‐arid regions of southern Africa. [ABSTRACT FROM AUTHOR]

Mammals in arid zones have to trade off thermal stress, predation pressure, and time spent foraging in a complex thermal landscape. We quantified the relationship between the environmental heat load and activity of a mammal community in the hot, arid Kalahari Desert. We deployed miniature black globe thermometers within the existing Snapshot Safari camera trap grid on Tswalu Kalahari Reserve, South Africa. Using the camera traps to record species' activity throughout the 24‐h cycle, we quantified changes in the activity patterns of mammal species in relation to heat loads in their local environment. We compared the heat load during which species were active between two sites with differing predator guilds, one where lion (Panthera leo) biomass dominated the carnivore guild and the other where lions were absent. In the presence of lion, prey species were generally active under significantly higher heat loads, especially during the hot and dry spring. We suggest that increased foraging under high heat loads highlights the need to meet nutritional requirements while avoiding nocturnal activity when predatory pressures are high. Such a trade‐off may become increasingly costly under the hotter and drier conditions predicted to become more prevalent as a result of climate change within the arid and semi‐arid regions of southern Africa. [ABSTRACT FROM AUTHOR]

Background: Centrally inserted central catheters (CICCs) are indispensable in modern healthcare, but unfortunately, come with complications. Catheter-related thrombosis is a well-known complication reported to occur in 5–30% of patients with CICC. There is a paucity of studies that report the incidence of catheter-related thrombosis after the introduction of real-time ultrasound insertion guidance as clinical practice. This study aimed to demonstrate any pathological macro- or microscopic changes in the vein wall associated with CICCs. Methods: The study was approved by the Swedish Ethical Review Authority and was conducted at a large university hospital. The study included 12 patients with a short-term CICC who were subject to autopsies. Vessels with inserted catheters were macroscopically and microscopically examined. Results: In total, seven female and five male patients with a median age of 70 (interquartile range 63–76) were included. With one exception, all patients received routine thromboprophylaxis throughout the period with CICC. Most inserted CICCs were 9.5 French (54%) and were inserted in the internal jugular vein (92%). The median time with CICC was seven days (interquartile range 1.8–20). At autopsy, thrombi were observed in all cases (100%), macroscopically and microscopically, attached to the distal portion of the CICC and/or the adjacent vessel wall. Inflammatory changes in the vessel walls were seen in all cases, and varying degrees of fibrosis were demonstrated in eight cases (67%). Conclusions: This autopsy study demonstrated that catheter-related thrombus formation with adjacent inflammatory and fibrotic vessel wall thickening was very common, despite a limited period of catheter use. The consequences of these findings are important, as thrombi may cause pulmonary embolism and possibly lead to catheter-related infections, and since inflammatory and fibrotic vessel wall thickening may evolve into chronic venous stenosis. Furthermore, the findings are a cause of concern, as CICCs are indispensable in modern healthcare and complications may be masked by the general disease that was the indication for CICC insertion. [ABSTRACT FROM AUTHOR]

Introduction: Chronic pain negatively impacts a range of sensory and affective behaviors. Previous studies have shown that the presence of chronic pain not only causes hypersensitivity at the site of injury but may also be associated with pain-aversive experiences at anatomically unrelated sites. While animal studies have indicated that the cingulate and prefrontal cortices are involved in this generalized hyperalgesia, the mechanisms distinguishing increased sensitivity at the site of injury from a generalized site-nonspecific enhancement in the aversive response to nociceptive inputs are not well known. Methods: We compared measured pain responses to peripheral mechanical stimuli applied to a site of chronic pain and at a pain-free site in participants suffering from chronic lower back pain (n  =  15) versus pain-free control participants (n  =  15) by analyzing behavioral and electroencephalographic (EEG) data. Results: As expected, participants with chronic pain endorsed enhanced pain with mechanical stimuli in both back and hand. We further analyzed electroencephalographic (EEG) recordings during these evoked pain episodes. Brain oscillations in theta and alpha bands in the medial orbitofrontal cortex (mOFC) were associated with localized hypersensitivity, while increased gamma oscillations in the anterior cingulate cortex (ACC) and increased theta oscillations in the dorsolateral prefrontal cortex (dlPFC) were associated with generalized hyperalgesia. Discussion: These findings indicate that chronic pain may disrupt multiple cortical circuits to impact nociceptive processing. [ABSTRACT FROM AUTHOR]

Objective: The type 1 interferon (IFN) pathway is up‐regulated in dermatomyositis (DM). We sought to define how organ‐specific disease activity as well as autoantibodies and other clinical factors are independently associated with systemic type I IFN activity in adult patients with DM. Methods: RNA sequencing was performed on 355 whole blood samples collected from 202 well‐phenotyped DM patients followed up during the course of their clinical care. A previously defined 13‐gene type I IFN score was modeled as a function of demographic, serologic, and clinical variables using both cross‐sectional and longitudinal data. Results: The pattern of type I IFN–driven transcriptional response was stereotyped across samples with a sequential modular activation pattern strikingly similar to systemic lupus erythematosus. The median type I IFN score was higher or lower in patients with anti–melanoma differentiation–associated protein 5 (anti–MDA‐5) or anti–Mi‐2 antibodies, respectively, compared to patients without these antibodies. Absolute type I IFN score was independently associated with muscle and skin disease activity, interstitial lung disease, and anti–MDA‐5 antibodies. Changes in the type I IFN score over time were significantly associated with changes in skin or muscle disease activity. Stratified analysis accounting for heterogeneity in organ involvement and antibody class revealed high correlation between changes in the type I IFN score and skin disease activity (Spearman's ρ = 0.84–0.95). Conclusion: The type I IFN score is independently associated with skin and muscle disease activity as well as certain clinical and serologic features in DM. Accounting for the effect of muscle disease and anti–MDA‐5 status revealed that the type I IFN score is strongly correlated with skin disease activity, providing support for type I IFN blockade as a therapeutic strategy for DM. [ABSTRACT FROM AUTHOR]

Purpose: The COVID-19 pandemic led to a drastic expansion in utilizing telemedicine, circumventing some of the geographical barriers to accessing pain care. However, uncertainties around the impact of telemedicine across various sociodemographic groups still exist, prompting further exploration. Therefore, this study aimed to evaluate the impact of sociodemographic factors in telemedicine utilization during and after the COVID-19 pandemic.Patients and methods: All outpatient non-procedural visits at the pain medicine division of a large academic institution in the epicenter of the pandemic (New York, USA), between March 2019 and October 2021, were retrospectively included. Sociodemographic data including gender, age, ethnicity/race, postal code, and type of health insurance, across three time periods associated with the COVID-19 pandemic - pre-lockdown (in-office visits only), lockdown (telemedicine visits only) and post-lockdown (offering both in-office and telemedicine visits) – were analyzed and compared.Results: In total, 12,615 unique patients - The majority being women (58%) - were seen during the whole study period. In the post-lockdown period, telemedicine was utilized by 42% of all patients. Follow-up visits, younger patients, white patients, patients residing further away from the hospital, and privately insured patients were more likely to utilize telemedicine post-lockdown (p < 0.05). Older patients, minorities, Manhattan residents, and Medicare/Medicaid recipients, were more likely to use in-office visits post-lockdown (p < 0.05).Conclusion: We identified disparities in the utilization of telemedicine in Pain Medicine, which may be due to socioeconomic factors such as lack of access to reliable internet access, cost of devices, and technological know-how. This emphasizes the need for further studies to better understand the reasons for and barriers to telemedicine use. This could help inform policymaking to safeguard equitable access to telemedicine use for pain care. [ABSTRACT FROM AUTHOR]

Machine learning is becoming an increasingly common component of routine data analyses in clinical research. The past decade in pain research has witnessed great advances in human neuroimaging and machine learning. With each finding, the pain research community takes one step closer to uncovering fundamental mechanisms underlying chronic pain and at the same time proposing neurophysiological biomarkers. However, it remains challenging to fully understand chronic pain due to its multidimensional representations within the brain. By utilizing cost-effective and non-invasive imaging techniques such as electroencephalography (EEG) and analyzing the resulting data with advanced analytic methods, we have the opportunity to better understand and identify specific neural mechanisms associated with the processing and perception of chronic pain. This narrative literature review summarizes studies from the last decade describing the utility of EEG as a potential biomarker for chronic pain by synergizing clinical and computational perspectives. [ABSTRACT FROM AUTHOR]

Background: The frequency of central venous catheter (CVC)‐related complications in hematologic patients has previously been studied but some uncertainty remains. Therefore, this observational cohort study was designed primarily to investigate mechanical and infectious complications related to CVC insertion in hematologic patients and secondarily to identify factors associated with these complications. Methods: Documented data on CVC insertions in all adult hematologic patients who received a CVC from 2013 to 2019 at a University Hospital in Sweden were retrospectively collected. Results: A total of 589 CVC insertions in 387 patients were included. The prevalence of moderate and severe mechanical complications, predominantly comprising grades 2–4 bleeding, was 11%. Preprocedural coagulopathy, number of needle passes, and arterial puncture were all independently associated with grades 2–4 bleeding. The incidence of suspected catheter‐related infections (sCRI) was 3.7/1000 catheter days. Higher body mass index and male gender were independently associated with sCRI. Conclusions: Patients with hematologic malignancies have a high risk of both grades 2–4 bleeding and sCRI after CVC insertion. This underlines the importance of optimizing the conditions at the insertion and also of daily inspections, evaluation of future needs, and extra precautions to avoid sCRI in these susceptible patients. [ABSTRACT FROM AUTHOR]

A woman in her 70s was referred for a painless plaque on the shin, present for 2 years and progressing in thickness. Examination revealed a large erythematous to violaceous indurated plaque with cobblestone appearance. Biopsy revealed an inflammatory infiltrate of neutrophils with scattered histiocytes, lymphocytes, eosinophils and plasma cells interspersed with areas of lamellar fibrosis and focal areas of vascular damage, suggestive of a localised chronic fibrosing vasculitis of the skin. Localised chronic fibrosing vasculitis is a rare dermatosis, typically presenting as ulcerated violet-red nodules, which can appear histologically similar to erythema elevatum diutinum (EED), which typically presents as red-brown annular plaques. EED may have a predominance of neutrophils and granulomas, while chronic fibrosing vasculitis may have a sparse infiltrate of mixed inflammatory cells without granulomas. While dapsone is a first-line treatment for EED, there are no formal guidelines on the treatment of localised chronic fibrosing vasculitis. Given the neutrophils in this sample and similarities with EED, this patient was treated with oral dapsone, resulting in plaque improvement. [ABSTRACT FROM AUTHOR]

Background: Radiation-associated angiosarcoma of the breast (RAASB) is a serious late consequence caused by breast cancer treatment. Initial symptoms are often inconspicuous, thus contributing to diagnostic delay. Most previous studies of the diagnostic aspects of RAASB are case reports. Purpose: To perform a complete review of the imaging findings and biopsy methods in a nationwide RAASB cohort. Material and Methods: RAASB patients were identified from a national cancer registry and additional patients were included from our hospital. All available information from imaging (mammogram [MGR], ultrasound [US], magnetic resonance imaging [MRI], and computed tomography [CT]) and biopsies was reviewed. The sensitivity of imaging and biopsy methods for detection of RAASB was calculated. Results: Fifty-eight patients with RAASB were found. Fourteen MGR, 30 US, 24 MRI, and 25 CT studies were available for evaluation. The sensitivity of MGR, US, MRI, and CT for detection of RAASB was 43%, 50%, 92%, and 84%, respectively. Superior sensitivity was demonstrated for punch biopsy (84%) and incisional biopsy (93%) compared to fine-needle aspiration cytology (0%) and core needle biopsy (18%). Conclusion: MRI and CT have comparable sensitivity for detection of RAASB, while MGR and US are unreliable. However, negative findings in MRI or CT must be interpreted with caution. Punch biopsy and incisional biopsy are the preferred biopsy methods. [ABSTRACT FROM AUTHOR]

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Background. In the past decade, the zebrafish community has widely embraced targeted mutagenesis technologies, resulting in an abundance of mutant lines. While many lines have proven to be useful for investigating gene function, many have also shown no apparent phenotype, or phenotypes not of interest to the originating lab. In order for labs to document and share information about these lines, we have created ZebraShare as a new resource offered within ZFIN. Methods. ZebraShare involves a form-based submission process generated by ZFIN. The ZebraShare interface (https://zfin.org/action/zebrashare) can be accessed on ZFIN under "Submit Data". Users download the Submission Workbook and complete the required fields, then submit the completed workbook with associated images and captions, generating a new ZFIN publication record. ZFIN curators add the submitted phenotype and mutant information to the ZFIN database, provide mapping information about mutations, and cross reference this information across the appropriate ZFIN databases. We present here examples of ZebraShare submissions, including phf21aa, kdm1a, ctnnd1, snu13a, and snu13b mutant lines. Results. Users can find ZebraShare submissions by searching ZFIN for specific alleles or line designations, just as for alleles submitted through the normal process. We present several potential examples of submission types to ZebraShare including a phenotypic mutants, mildly phenotypic, and early lethal mutants. Mutants for kdm1a show no apparent skeletal phenotype, and phf21aa mutants show only a mild skeletal phenotype, yet these genes have specific human disease relevance and therefore may be useful for further studies. The p120-catenin encoding gene, ctnnd1, was knocked out to investigate a potential role in brain development or function. The homozygous ctnnd1 mutant disintegrates during early somitogenesis and the heterozygote has localized defects, revealing vital roles in early development. Two snu13 genes were knocked out to investigate a role in muscle formation. The snu13a;snu13b double mutant has an early embryonic lethal phenotype, potentially related to a proposed role in the core splicing complex. In each example, the mutants submitted to ZebraShare display phenotypes that are not ideally suited to their originating lab's project directions but may be of great relevance to other researchers. Conclusion. ZebraShare provides an opportunity for researchers to directly share information about mutant lines within ZFIN, which is widely used by the community as a central database of information about zebrafish lines. Submissions of alleles with a phenotypic or unexpected phenotypes is encouraged to promote collaborations, disseminate lines, reduce redundancy of effort and to promote efficient use of time and resources. We anticipate that as submissions to ZebraShare increase, they will help build an ultimately more complete picture of zebrafish genetics and development. [ABSTRACT FROM AUTHOR]

During the coronavirus disease 2019 (COVID-19) pandemic, there has been a rise in the diagnosis of acral lesions, including chilblainslike lesions, ischemia, and retiform purpura. Understanding the differences in presentation and severity of illness between children and adult patients is important for physicians to understand risk stratification and management of these lesions. We reviewed the literature on the acral lesions seen in children and adults with COVID-19 infection to offer guidelines for diagnosis and treatment. [ABSTRACT FROM AUTHOR]

We report a case of differentiation syndrome in a patient receiving the IDH1 inhibitor ivosidenib, with skin biopsy showing isocitrate dehydrogenase (IDH) R132H‐mutated leukemia cutis. A 72‐year‐old man with IDH1‐mutated acute myeloid leukemia (AML), status‐post allogeneic cell transplantation, on ivosidenib for 6 months, was admitted for culture‐negative neutropenic fever, pink and purpuric plaques and patches on the legs, abdomen and back, edema, hypotension, and shortness of breath. Skin biopsy revealed an infiltrate of atypical, immature, myeloperoxidase‐positive mononuclear cells compatible with leukemia cutis or Sweet syndrome. Although dermal edema and interstitial neutrophilic infiltrate with karyorrhexis characteristic of Sweet syndrome were not seen, the atypical cells lacked expression of CD117 and CD34, which were expressed in the original leukemia. Additional immunohistochemical staining of suspected blasts was strongly positive for IDH1 R132H, suggesting a diagnosis of leukemia cutis. As the immunophenotype of blasts in skin infiltrates can significantly differ from the immunophenotype seen in blood and bone marrow, this case shows that mutation‐specific antibodies such as anti‐IDH1 R132H may be useful to help distinguish malignant from non‐malignant infiltrates in the skin. Furthermore, differentiation syndrome may show histopathologic features of leukemia cutis on skin biopsy. [ABSTRACT FROM AUTHOR]

Background: Radiation-associated angiosarcoma of the breast (RAASB) is an aggressive malignancy that is increasing in incidence. Only a few previous population-based studies have reported the results of RAASB treatment. Methods: A search for RAASB patients was carried out in the Finnish Cancer Registry, and treatment data were collected to identify prognostic factors for survival. Results: Overall, 50 RAASB patients were identified. The median follow-up time was 5.4 years (range 0.4–15.6), and the 5-year overall survival rate was 69%. Forty-seven (94%) patients were operated on with curative intent. Among these patients, the 5-year local recurrence-free survival, distant recurrence-free survival, and overall survival rates were 62%, 75%, and 74%, respectively. A larger planned surgical margin was associated with improved survival. Conclusions: We found that the majority of RAASB patients were eligible for radical surgical management in this population-based analysis. With radical surgery, the prognosis is relatively good. [ABSTRACT FROM AUTHOR]

Chronic cutaneous graft‐vs‐host disease (GVHD) has several atypical variants. We describe two cases of GVHD with clinical and histopathologic features of pityriasis rubra pilaris (PRP), which responded to additional immunosuppression. Recognition of this newly described PRP‐like clinical presentation of GVHD may prompt early consideration of additional steroid‐sparing therapies. [ABSTRACT FROM AUTHOR]

Abstract: Radiation‐associated sarcoma (RAS) is a rare complication of radiation therapy (RT) to breast cancer (BC). This study explored RAS after RT to BC in a nationwide population‐based material. The Finnish Cancer Registry was queried for patients with BC treated during 1953‐2014 who were later diagnosed with a secondary sarcoma in 1953‐2014. Registry data, patient files, and sarcoma specimens were  analyzed to confirm diagnosis and location of RAS at or close to the RT target volume. A total of 132 512 patients were diagnosed with invasive BC during the study period. A subsequent sarcoma was diagnosed in 355 patients. After exclusion, 96 RAS were identified. Angiosarcoma (AS) was the most prevalent histology in 50 (52%) of 96 patients. However, the first radiation‐associated AS was diagnosed in a patient treated for BC with breast‐conserving surgery in 1984, and thereafter, the proportion of AS continuously increased. The 5‐year sarcoma‐specific survival was 75.1% for RAS treated with a curative intent. The distribution of histologic subtypes of RAS has changed during the 60 years of this registry study. The first radiation‐associated AS was diagnosed in 1989, and presently, AS is the most common histologic subtype of RAS. It is possible that changes in BC treatment strategies are influencing the characteristics of RAS. [ABSTRACT FROM AUTHOR]

The article has analytical and conceptual character. It contains a detailed analysis of the scope of cadastral information on waters based on actual data from the regional databases, which are established in four logistically major cities in Poland: Warsaw, Krakow, Wroclaw and Szczecin. The authors examine the contents of water cadastre databases in Poland and possibilities of using them in building the 3D cadastre. The concept of using water cadastre as a subsystem of the 3D cadastre presented in the work was carried out using graphical methods of the object-oriented analysis. The authors present a Real Estate Cadastre (REC) model based on synchronisation of the Land Register databases with the water cadastre databases carried out in District Water Management Boards. Modernisation and thematic expansion of Land Register databases, which act in Poland as cadastre, consistent with the presented REC model is a chance to improve the real estate market in Poland. [ABSTRACT FROM AUTHOR]

Land fragmentation is a phenomenon which constitutes one of the biggest obstacles to profitable agricultural production. Measurable estimation of this phenomenon is possible by a number of known indicators, based on the surface area of parcels in the given area, their location in space and belonging to individual farms. This method of calculation of the indicators is inaccurate due to the phenomenon of neighbourhood of plots which belong to the same owners. For the purposes of calculating the ratios of actual fragmentation of land, these parcels should be treated as one complex. The article presents a proposal for the adjustment of existing methods of determination of the fragmentation of land indicators, taking into account these phenomena. The object of the research covered area of the voivodeship of Malopolska located in the southern part of Poland. Developed by the authors, method of calculation of land fragmentation indicators, based on complexes of land belonging to the same owners (complexes of plots aggregation), gives very good results in the evaluation of the intensity of the land fragmentation. Obtained in this way, indicator's land fragmentation represents the real situation on the ground. [ABSTRACT FROM AUTHOR]

Background and purpose -- Soft-tissue sarcoma (STS) is rare, with challenging individualized treatment, so diagnostics and treatment should be centralized. Historical controls are sometimes used for investigation of whether new diagnostic or therapeutic tools affect patient outcome. However, as yet unknown factors may affect the outcome. We investigated prognostic factors and prognosis in 2 nationwide cohorts of patients diagnosed with a local STS during the periods 1998-2001 and 2005-2010, with special interest in finding factors lying behind possible improvement of prognosis. Patients and methods -- 2 cohorts of patients with STS of the extremities or trunk diagnosed during the periods 1998-2001 and 2005-2010 were retrieved from the nationwide Finnish Cancer Registry. Detailed information was gathered from patient files. Results -- Compared to first cohort, a larger proportion of patients with inadequate surgery in the second cohort received radiation therapy, and both the local control rate and the sarcoma-specific survival rate improved in the second cohort. For sarcoma-specific survival, cohort (HR = 0.6, 95% CI: 0.5-0.9), age, depth, grade, and margin were significant factors in multivariate analysis. For local control, cohort (HR = 0.6, 95% CI: 0.5- 0.9), age, and margin were significant in multivariate analysis. Interpretation -- Known prognostic factors including type of treatment did not entirely explain the secular trend of continuous improvement in prognosis in STS. This illustrates the danger of using historical controls for investigation of whether new diagnostic or therapeutic tools have an effect on patient outcome. [ABSTRACT FROM AUTHOR]

The association of malignant lymphomas with non-necrotic epithelioid granulomas has been reported rarely since 1977. Hodgkin's disease-associated widespread cutaneous granuloma annulare (GA) has been reported in only eight patients. We report the second case of subcutaneous GA associated with Hodgkin's disease. A 73-year-old man with Epstein-Barr virus-associated Hodgkin's lymphoma and paraneoplastic subcutaneous GA, presented 3 months after the diagnosis of malignancy. Examination revealed a large, broad erythematous, indurated, subcutaneous plaque spanning the majority of the left lower back and flank with no associated symptoms. Initial biopsy was suggestive of morphea. Prompted by positron emission tomography (PET) findings of increased fluorodeoxyglucose (FDG) uptake, a second, deeper biopsy was performed, revealing subcutaneous palisaded granulomatous dermatitis. After complete workup, the diagnosis most strongly suggested subcutaneous GA. This case highlights the importance of deep incisional biopsies, the fluorodeoxyglucose - positron emission tomography (FDG-PET) findings in GA and the rare association of GA with Hodgkin's disease which may signal the presence of malignancy. [ABSTRACT FROM AUTHOR]

ABSTRACT This study explored the use of the α2C-adrenoceptor PET tracer [11C]ORM-13070 to monitor α2C-AR occupancy in the human brain. The subtype-nonselective α2-AR antagonist atipamezole was administered to eight healthy volunteer subjects to determine its efficacy and potency ( Emax and EC50) at inhibiting tracer uptake. We also explored whether the tracer could reveal changes in the synaptic concentrations of endogenous noradrenaline in the brain, in response to several pharmacological and sensory challenge conditions. We assessed occupancy from the bound-to-free ratio measured during 5-30 min post injection. Based on extrapolation of one-site binding, the maximal extent of inhibition of striatal [11C]ORM-13070 uptake ( Emax) achievable by atipamezole was 78% (95% CI 69-87%) in the caudate nucleus and 65% (53-77%) in the putamen. The EC50 estimates of atipamezole (1.6 and 2.5 ng/ml, respectively) were in agreement with the drug's affinity to α2C-ARs. These findings represent clear support for the use of [11C]ORM-13070 for monitoring drug occupancy of α2C-ARs in the living human brain. Three of the employed noradrenaline challenges were associated with small, approximately 10-16% average reductions in tracer uptake in the dorsal striatum (atomoxetine, ketamine, and the cold pressor test; P < 0.05 for all), but insulin-induced hypoglycemia did not affect tracer uptake. The tracer is suitable for studying central nervous system receptor occupancy by α2C-AR ligands in human subjects. [11C]ORM-13070 also holds potential as a tool for in vivo monitoring of synaptic concentrations of noradrenaline, but this remains to be further evaluated in future studies. Synapse 69:172-181, 2015. © 2014 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Desmoid tumours are uncommon non-malignant tumours that show a locally aggressive growth pattern and a high local recurrence rate after surgery. Approximately 10% of the desmoid tumours are associated with familial adenomatous polyposis (FAP). Variable natural history of the disease challenges treatment decision-making in the absence of prospective, randomised data. Association of this rare tumour to GIST is speculated and the tumorigenesis may share common steps. This study reviews given treatment and reports prognostic factors for local control and concurrent neoplasms in patients evaluated by a single soft tissue tumour group. Patients referred to the soft tissue tumour group at Helsinki University Central Hospital (HUCH) for a desmoid tumour (primary or recurred) during 1987-2007 and receiving surgical treatment with or without adjuvant treatment were included in this retrospective review. All locations and also patients with a FAP-associated tumour were included. Extra-abdominal location showed lower local control despite the fact that 27% of patients also received radiation therapy. One amputation was performed. Female sex and location in the rectus abdominis muscle predicted improved local control in multivariate analysis. In this review, the occurrence (14%) of concurrent neoplasms was higher than expected with unusual tumour types noted including two GISTs. In those patients in whom surgical treatment is chosen, adjuvant radiation therapy should also be considered in order to decrease morbidity from aggressive surgery aiming at R0 resection. Further studies are suggested to illuminate the biological association between the desmoid tumour and other neoplasms. [ABSTRACT FROM AUTHOR]

Background. Most local recurrences have developed in the clinical target volume in previously published series after combined modality treatment for soft tissue sarcoma. However, marginal misses were seen in almost 20% of the patients. The aim of the present study was to determine the location of the recurrence and the total dose at the centre point of the local recurrence for future radiation therapy planning. Material and methods. We included only patients with images in digital form, during 1999-2006 (n = 17), treated for soft tissue sarcoma with combined surgical therapy and radiotherapy at Helsinki University Central Hospital. Image fusion was used to determine the location of the recurrence in relation to radiation therapy target. Results. In the present study utilising digital image fusion, in patients with 3D CT-based radiation treatment planning the risk of marginal miss was low as only one patient of 17 relapsed outside the target. Estimated mean radiation dose at the site of local recurrence was 49.1 Gy in patients with positive margins and 48.1 Gy in patients with negative margins. Conclusion. The risk of marginal miss in soft tissue sarcoma is low after modern 3D planned radiation treatment combined with surgery. More generous use of boost might improve in-target local control. [ABSTRACT FROM AUTHOR]

It is possible that BP presents more frequently than PV as an ICI-related toxicity due to the relatively more exposed location of hemidesmosomes at the DEJ compared to desmosomes, which increases the frequency of BP antigen exposure and subsequent antibody formation. Bullous disorders associated with anti-PD-1 and anti-PD-L1 therapy: a retrospective analysis evaluating the clinical and histopathologic features, frequency, and impact on cancer therapy. [Extracted from the article]

Background. A prospective diagnostics and treatment protocol for extremity and trunk wall soft tissue sarcoma (STS) was introduced by the Scandinavian Sarcoma Group in 1986 and it was also widely adopted in Finland. We have updated the protocol and made it more detailed at the Helsinki University Central Hospital. We retrospectively compared diagnostics and treatment of STS in a nationwide population-based material to this protocol with special emphasis on local control. Methods. Data for 219 patients with an STS of extremity or trunk wall diagnosed during 1998-2001 was retrieved from the nationwide Finnish Cancer Registry. Histologic review was performed. Treatment centres were divided into high-, intermediate- and low-volume centres based on the number of patients with final surgery during the study period. Results. Significantly more patients were operated with a preoperative histological or cytological diagnosis at high-volume centres. No preoperative diagnosis was a strong predictor for the patient to undergo more than one operation (p < 0.0001). Wide surgical margin was achieved more often at high-volume centres, but in all centre categories a considerable percentage of patients with inadequate surgical margin did not receive adjuvant radiation therapy. Local control at five years was 82% at high-volume centres, 61% at intermediate-volume centres treating highest percentage of deep tumours and 69% at low-volume centres (p = 0.046). Local control improved as the number of patients operated (surgical volume of the centre) increased. Conclusion. The present quality-control study is the first nationwide population-based study to assess diagnostics and treatment of STS. When referred to a specialised sarcoma centre even patients with inadequate surgery can achieve good local control. STS is a rare cancer and its treatment should be centralised in Finland, which has 5.4 million inhabitants and approximately 100 new STSs of extremities and trunk wall annually. [ABSTRACT FROM AUTHOR]

Tarsal adhesive pads are crucial for the ability of insects to traverse their natural environment. Previous studies have demonstrated that for both hairy and smooth adhesive pads, significant reduction in adhesion can occur because of contamination of these pads by wax crystals present on plant surfaces or synthetic microspheres. In this paper, we focus on the smooth adhesive pads of ants and study systematically how particulate contamination and the subsequent loss of adhesion depends on particle size, particle surface energy, humidity and species size. To this end, workers of ant species Polyrhachis dives and Myrmica scabrinodis (Hymenoptera; Formicidae) were presented with loose synthetic powder barriers with a range of powder diameters (1-500 μm) and surface energies (PTFE or glass), which they would have to cross in order to escape the experimental arena. The barrier experiments were conducted for a range of humidities (10-70%). Experimental results and scanning electron microscopy confirm that particulate powders adversely affect the adhesive ability of both species of ant on smooth substrates via contamination of the arolia. Specifically, the loss of adhesion was found to depend strongly on particle diameter, but only weakly on particle type, with the greatest loss occurring for particle diameters smaller than the claw dimensions of each species, and no effect of humidity was found. We also observed that ants were repelled by the powder barriers which led to a decrease of adhesion prior to their eventual crossing, suggesting that insect antennae may play a role in probing the mechanical fragility of substrates before crossing them. [ABSTRACT FROM AUTHOR]

We investigated the effects of lifelong voluntary exercise on articular cartilage of mice. At the age of 4 weeks C57BL mice ( n == 152) were divided into two groups, with one group serving as a sedentary control whereas the other was allowed free access to a running wheel from the age of 1 month onward. Mice were euthanized at four different time points (1, 2, 6, and 18 months of age). Articular cartilage samples were gathered from the load-bearing area of the tibial medial plateaus, and osteoarthritis was graded. Additionally, the proteoglycan content distribution was assessed using digital densitometry, collagen fibril orientation, and parallelism with polarized light microscopy, and collagen content using Fourier transform infrared imaging spectroscopy. The incidence of osteoarthritis increased with aging, but exercise had no effect on this trend. Furthermore, the structure and composition revealed significant growth, maturation, and age-dependent properties. Exercise exerted a minor effect on collagen fibril orientation in the superficial zone. Fibril orientation at 2 months of age was more perpendicular to surface ( p < 0.05) in controls compared with runners, whereas the situation was reversed at the age of 18 months ( p < 0.05). The collagen content of the superficial zone was higher ( p < 0.01) at the age of 18 months in controls compared with runners but the proteoglycan content did not display any exercise-dependent changes. In conclusion, growth, maturation, and aging exerted a clear effect on integrity, structure, and composition of medial tibial plateau articular cartilage in mice, whereas lifelong voluntary exercise had only a minor effect on collagen architecture and content. [ABSTRACT FROM AUTHOR]

Objective: To determine the number of participants required in controlled clinical trials investigating the progression of osteoarthritis (OA) of the hip as evaluated by the joint space width (JSW) on radiographs and to evaluate the reproducibility of the JSW measurement methods.Materials and Methods: Anteroposterior radiographs of hip were taken from 13 healthy volunteers and from 18 subjects with radiographic hip OA. The reproducibility of the JSW was determined from four segments using digital caliper measurements performed on film radiographs and using semiautomatic computerized image analysis of digitized images. Pearson correlation coefficient, coefficient of variability [CV (%)], and sample size values were calculated.Results: It was found that 20 was a typical number of patients for a sufficiently powered study. The highest sample size was found in subjects with OA in the lateral segment. The reproducibility of the semiautomatic computerized method was not significantly better than the digital caliper method.Conclusion: The number of study subjects required to detect a significant joint space narrowing in follow-up studies is influenced by the baseline hip joint OA severity. The JSW measurements with computerized image analysis did not improve the reproducibility and thus performing JSW measurements with a digital caliper is acceptable. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to undertake a stereological analysis to quantify the dimensions of the collagen network in the repair tissue of porcine joints after they had been subjected to autologous chondrocyte transplantation (ACT). Method: ACT was used to repair cartilage lesions in knee joints of pigs. Electron-microscopic stereology, immunostaining for type II collagen, and quantitative polarized-light microscopy were utilized to study the collagen fibrils in the repair tissue 3 and 12 months after the operation. Results: The collagen volume density (VV) was lower in the repair tissue than in normal cartilage at 3 months (20.4 vs. 23.7%) after the operation. The collagen surface density (SV, 1.5·10-2 vs. 3.1·10-2 nm2/nm3) and VV increased with time in the repair tissue (20.4 vs. 44.7%). Quantitative polarized-light microscopy detected a higher degree of collagen parallelism in the repair tissue at 3 months after the operation (55.7 vs. 49.7%). In contrast, 1 year after the operation, fibril parallelism was lower in the repair tissue than in the control cartilage (47.5 vs. 69.8%). Conclusion: Following ACT, VV and SV increased in the repair tissue with time, reflecting maturation of the tissue. One year after the operation, there was a lower level of fibril organization in the repair tissue than in the control cartilage. Thus, the newly synthesized collagen fibrils in the repair tissue appeared to form a denser network than in the control cartilage, but the fibrils remained more randomly oriented. Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

In this paper, we present the OPUS (optoacoustic plus ultrasound) system, which is a combination of a wavelength-tunable pulsed optical parametrical oscillator (OPO) laser with a commercial ultrasound (US) scanner. Optoacoustic (OA) or, synonymously, photoacoustic (PA) imaging is a spectroscopic technique to measure optical absorption in semitransparent solids and liquids. The measured signal is an acoustical pressure wave, which represents the absorption of pulsed optical radiation. By temporally and spatially resolved detection of the pressure wave on the sample surface, a 2D or even 3D image of the distribution of the optical absorption in the sample can be generated. In recent years, OA tomography has found increasing application in medical imaging. Most of these applications are based on qualitative OA imaging. The reported system is intended primarily for breast cancer detection, in which the optoacoustic imaging modality offers additional information to the ultrasound image. Consequently, the system is developed in a way that the OA imaging mode can be installed without major changes to the US instrument. The capabilities of the OPUS system for the quantitative analysis of absorber concentrations in tissue models are exploited. [ABSTRACT FROM AUTHOR]

Purpose: Catechol-O-methyl transferase (COMT) is a pivotal regulator of brain dopamine function with a region-specific role. COMT is important in dopamine elimination in the prefrontal cortex, whereas dopamine reuptake is the main mechanism for synaptic removal of dopamine in the striatum. We studied whether the functional COMT gene polymorphism (Val158Met) associates with altered dopamine D2 receptor binding characteristics in vivo hypothesizing an effect in the cortex but not in the striatum.Procedures: Samples of 38 and 45 Finnish healthy subjects scanned previously with PET and the D2/D3 receptor radioligands [(11)C]FLB457 or [(11)C]raclopride, respectively, were genotyped for the Val158Met polymorphism.Results: No significant associations were found between the Val158Met genotype and D2 receptor binding characteristics in the cortex or the striatum as measured with [(11)C]FLB457 and [(11)C]raclopride, respectively.Conclusions: COMT genotype is not related with alterations in baseline D2 receptor availability in vivo in the cortex or the striatum. This information is useful for the interpretation of genetic studies on COMT in neuropsychiatry. [ABSTRACT FROM AUTHOR]

The aim of this study was to record growth-related changes in collagen network organization and proteoglycan distribution in intermittently peak-loaded and continuously lower-level-loaded articular cartilage. Cartilage from the proximal phalangeal bone of the equine metacarpophalangeal joint at birth, at 5, 11 and 18 months, and at 6–10 years of age was collected from two sites. Site 1, at the joint margin, is unloaded at slow gaits but is subjected to high-intensity loading during athletic activity; site 2 is a continuously but less intensively loaded site in the centre of the joint. The degree of collagen parallelism was determined with quantitative polarized light microscopy and the parallelism index for collagen fibrils was computed from the cartilage surface to the osteochondral junction. Concurrent changes in the proteoglycan distribution were quantified with digital densitometry. We found that the parallelism index increased significantly with age (up to 90%). At birth, site 2 exhibited a more organized collagen network than site 1. In adult horses this situation was reversed. The superficial and intermediate zones exhibited the greatest reorganization of collagen. Site 1 had a higher proteoglycan content than site 2 at birth but here too the situation was reversed in adult horses. We conclude that large changes in joint loading during growth and maturation in the period from birth to adulthood profoundly affect the architecture of the collagen network in equine cartilage. In addition, the distribution and content of proteoglycans are modified significantly by altered joint use. Intermittent peak-loading with shear seems to induce higher collagen parallelism and a lower proteoglycan content in cartilage than more constant weight-bearing. Therefore, we hypothesize that the formation of mature articular cartilage with a highly parallel collagen network and relatively low proteoglycan content in the peak-loaded area of a joint is needed to withstand intermittent stress and shear, whereas a constantly weight-bearing joint area benefits from lower collagen parallelism and a higher proteoglycan content. [ABSTRACT FROM AUTHOR]

The C957T polymorphism of the human dopamine D2 receptor gene ( DRD2) regulates DRD2 availability in striatum in vivo. Specifically, the T allele predicts high DRD2 availability in healthy volunteers (T/T>T/C>C/C). However, this finding was unexpected as in vitro the T allele is associated with a decrease in DRD2 mRNA stability and synthesis of the receptor through a putative alteration in the receptor mRNA folding. To elucidate further how changes in DRD2 density ( Bmax) and affinity ( KD) contribute to the differences in DRD2 availability between the C957T genotypes, we studied these parameters separately in a sample of 45 healthy volunteers. The subjects had two PET scans with [11C]raclopride (high and low specific radioactivity scans) for the estimation of Bmax and KD, and were genotyped for the C957T. Moreover, the role of the related and previously studied functional TaqIA polymorphism of ankyrin repeat and kinase domain containing 1 ( ANKK1) gene was reassessed for comparative purposes. The results indicate that the C957T increased binding potential by decreasing DRD2 KD (C/C>C/T>T/T), while Bmax was not significantly altered. These preliminary findings indicate that the C957T genotype-dependent changes in DRD2 availability are driven by alterations in receptor affinity and putatively in striatal dopamine levels. This mechanism seems to differ from that observed previously for the ANKK1 gene TaqIA polymorphism, where the minor allele (A1) affects DRD2 availability predominantly by changing Bmax. The hypothesis that the two SNPs may have independent effects on dopamine neurotransmission needs to be further tested. Synapse 63:907-912, 2009. © 2009 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

We investigated the effects of exercise-induced loading on the collagen network of equine articular cartilage. Collagen fibril architecture at a site (1) subjected to intermittent high-intensity loading was compared with that of an adjacent site (2) sustaining continuous low-level load. From horses exposed to forced exercise (CONDEX group) or not (PASTEX group), the spatial parallelism of fibrils and the orientation angle between fibrils and the surface at depths 9 µm apart through cartilage from surface to tidemark were determined using polarized light microscopy, and expressed as parallelism index (PI) and orientation index (OI). PI was significantly higher in site 2 than 1 in CONDEX and PASTEX groups. PI was significantly higher in forced exercised horses at site 2 but not site 1. OI was significantly greater (more perpendicular to the surface) in the superficial and deep cartilage of site 2 than 1 in both CONDEX and PASTEX groups. Superficial zone OI was higher in exercised horses at site 1 but not at site 2. Exercise increased collagen parallelism and affected orientation. The site differences in OI indicate that Benninghoff's classic predominantly perpendicular arcades appear not to be a consistent architectural feature, but adapt to local forces sustained. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res [ABSTRACT FROM AUTHOR]

Planar optical waveguides fabricated in erbium doped glasses are promising photonics components operating at 1.5 μm, above all as optical amplifiers or waveguide lasers. In this study we focused on the influence of chemical compositions of Er3+ and Er3+/Yb3+-doped silicate glasses on the properties important for the sought applications, i.e., waveguiding and spectroscopic properties of the fabricated waveguides. Optical waveguides were fabricated by routine K+ ↔ Na+ ion exchange in a set of the glasses that had various contents of the RE ions. Waveguiding properties were studied by means of Dark Mode Spectroscopy at 671 nm while the chemical composition of the waveguides was determined using Scanning Electron Microscopy (SEM-EDAX). Surface concentrations of the lasing RE ions were determined by Rutherford Backscattering Spectroscopy (RBS) and related to the resultant photoluminescence properties. On the bases of the obtained experimental results the relations between composition of the substrates, especially content of the active ions, and experimental procedures will be presented with regards to real fabrication processes. Diffusion processes will be characterized by diffusion coefficients. [ABSTRACT FROM AUTHOR]

Background and purpose There have only been a few nationwide studies on the epidemiology and outcome of osteosarcoma. We report the clinical features, treatment, and prognosis of osteosarcoma in Finland for the period 1971-1990. Methods The study material was derived from popu-lation-based data from the national Finnish Cancer Registry. 302 osteosarcomas were reported during the study period. Histological slides could be retrieved for 199 cases and from histological re-examination, 139 (83%) of these cases were confirmed as osteosarcoma and were included in the analysis. The mean length of follow-up was 8 (0.1-28) years. Results The overall 5-year survival for the whole study population was 58%, with an improvement in survival during 1981-1990 (65%) compared to the period 1971-1980 (47%) (p=0.01). More chemotherapy was administered in the later time period. For metastasis-free survival, diagnosis in the 1970s as opposed to the 1980s (p=0.01) and large tumor size worsened outcome in univariate analysis. Patients who developed metastatic relapse within 10 months of the diagnosis had worse sarcoma-specific survival than those who developed metastases later. Limb-salvage surgery increased from 12% to 23% for patients with a peripheral tumor, with no increase in local relapses. Interpretation We recommend aggressive approach to treat recurrent disease, with a view to further improving survival. In a small country such as Finland it is necessary to concentrate treatment to only a few centers, to ensure a high quality of treatment. [ABSTRACT FROM AUTHOR]