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Genetic polymorphisms of rs9949644 in MAPK4 are associated with clinical response to methotrexate in patients with psoriasis.
No full textBackground The study aimed to investigate the relationship of MAPK4 genetic variants with the efficacy of MTX in psoriasis patients. Methods Patients treated with MTX were classified as responders or nonresponders if the Psoriasis Area and Severity Index (PASI) at week 12 was reduced to greater than 75% or lower than 75%, respectively. The genotypes of 14 MAPK4 single nucleotide polymorphisms (SNPs) in 310 patients were analyzed. The expression levels of MAPK4 protein were detected by western blot. Results Only rs9949644 polymorphisms were associated with the efficacy after adjusting for the confounding factors. Patients with the rs9949644 AG or GG genotype had a better clinical response compared to patients with the AA genotype. Rs9949644 polymorphisms were significantly associated with the PASI improvement rate. Besides, the protein level of MAPK4, positively associated with the psoriasis severity, was higher in patients. There were no significant differences of MAPK4 protein levels among three groups. While after treatment, MAPK4 levels in the AG or GG group showed a significantly down-regulated trend. Conclusions By demonstrating the significant association of MAPK4 with the efficacy of MTX, this study indicates that MAPK4 may be involved in the psoriasis progression and act as a predictor of therapeutic response
Angiostrongylus dujardini infection in a coconut lorikeet (Trichoglossus haematodus) from a zoological garden in Switzerland.
Get PDFAngiostrongylus spp. (Metastrongyloidea) can cause severe disease in several animal species and humans. This report describes an infection with Angiostrongylus dujardini in a captive Coconut lorikeet (Trichoglossus haematodus) from a zoo in Switzerland. The bird was reported being attacked by conspecifics, removed from the flock, and hospitalized. It showed lethargy, moderately reduced body condition, and lack of reaction to visual stimuli. Analgesic and antibiotic treatment were initiated but because of worsening of its general condition the bird was euthanized the following day. Necropsy revealed multifocal, subcutaneous hemorrhages, diffusely reddened lungs and a moderately dilated right heart with several intraluminal nematodes embedded in a coagulum. Four worms were collected and microscopically examined. They were identified as adult females, measuring 19-21 mm long x 0.4-0.5 mm wide, with general morphological and morphometric characteristics consistent with angiostrongylid nematodes. In lung sections, multifocal collection of thin-walled embryonated eggs in variable stages of development was observed along with fully developed nematode larvae within the lumina of alveoli and lung vessels. Associated granulomatous infiltrates indicated a severe, multifocal, chronic, granulomatous pneumonia. The diagnosis of A. dujardini infection was formulated by morphological examination of adult and larval stages, supported by molecular analysis (PCR-amplification and sequencing of the ITS2, 5.8S and 28S rDNA flanking regions). This is the first report of A. dujardini infection in an avian species, providing evidence that birds can serve as accidental hosts of this parasite in addition to mammals, and that the parasite can reach maturity and multiply in the avian cardiorespiratory system
Guidelines and practice of breastfeeding in women living with HIV-Results from the European INSURE survey.
No full textINTRODUCTION
Antiretroviral therapy (ART) is integral to HIV prevention, including averting vertical transmission. The World Health Organization (WHO) recommends ART and breastfeeding for all women living with HIV for at least 12 months post-partum [1, 2]. Much of the data on HIV transmission through breastfeeding comes from low-resource settings, with a paucity of data on breastfeeding-related HIV transmission in women living with HIV in other settings. Women Against Viruses in Europe (WAVE), part of the European AIDS Clinical Society (EACS), aims to improve the standard of care for women living with HIV and sought to gain an understanding of breastfeeding guidelines and practice in women living with HIV across Europe.
METHODS
A steering group convened by WAVE developed a survey to collate information on breastfeeding trends, practice, and guideline recommendations for women living with HIV in Europe and to establish interest in becoming involved in a collaborative breastfeeding network. The survey was disseminated to 31 countries in March 2022.
RESULTS
In total, 25 eligible responses were received: 23/25 (92%) countries have HIV and pregnancy guidelines; 23/23 (100%) guidelines refer specifically to breastfeeding; 12/23 (52%) recommend against breastfeeding; 11/23 (48%) offer an option if certain criteria are met; 12/25 (48%) reported that the number of women living with HIV who breastfeed is increasing; 24/25 (96%) respondents were interested in joining a network on breastfeeding in women living with HIV.
CONCLUSIONS
Recommendations vary, and nearly half of the guidelines recommend against breastfeeding. Many countries report an increase in breastfeeding. WAVE will establish a collaborative network to bridge data gaps, conduct research, and improve support for women living with HIV who choose to breastfeed
Linking Forest Ecosystem Services to the SDGs: Semi-quantitative Mapping of Perceptions towards Integrated Decision-making.
Get PDFWith this study, we test and present the results of a reproducible semi-quantitative methodological approach, which enables us to map perceptions of complex systems, linking the forest ecosystem services (FES) of a given spatial level to the wider policy domains represented by the 2030 Agenda and its Sustainable Development Goals (SDGs). Through a participative process, we used integrated forest management and FES as entry point concepts to support and inform dialog towards a normative desired future as framed by the SDGs, taking into account interdependencies across sectors and policy domains. The scales used in the test were national (Switzerland) and international but it is possible to use the approach at any level of integration, especially the landscape one in the case of forest or other ecosystem issues to be transdisciplinary solved. We stress that the semi-quantitative aspects of the approach - be it the ranking of the importance of FES across the different SDGs, or the positive or negative weighting of interactions among these FES in cross-impact matrices - enable the perceptions held by actors to be more explicit and significant for governance or goal prioritization. The results illustrate the perceptions of selected actors on the effects of integrated forest management and provide a basis for multi-actor deliberation on emerging potential synergies or conflicts, thereby genuinely supporting science-policy-practice dialog, which is crucial to foster integrated decision-making
1,2,3,4-Tetrafluorobiphenylene: A Prototype Janus-Headed Scaffold for Ambipolar Materials.
No full textThe title compound was synthesized by Ullmann cross-coupling in low yield as first representative of [n]phenylene containing hydrocarbon and fluorocarbon rings. Stille / Suzuki-Miyaura cross-coupling reactions, as well as substitution of fluorine in suitable starting compounds, failed to give the same product. The geometric and electronic structures of the title compound were studied by X-ray diffraction, cyclic voltammetry and density functional theory calculations, together with Hirshfeld surface and reduced density gradient analyses. The crystal structure features head-to-tail π-stacking and other fluorine-related secondary bonding interactions. From the nucleus-independent chemical shifts (NICS) descriptor, the four-membered ring of the title compound is antiaromatic, and the six-membered rings are aromatic. The Janus molecule is highly polarized; and the six-membered fluoro- and hydrocarbon rings are Lewis π-acidic and π-basic, respectively. The electrochemically-generated radical cation of the title compound is long-lived as characterized by electron paramagnetic resonance, whereas the radical anion is unstable in solution. The title compound reveals electrical properties of an insulator. On expanding its molecular scaffold towards partially fluorinated [n]phenylenes (n ≥ 2), the properties presumably can be transformed into those of semiconductors. In this context, the title compound is suggested as a prototype scaffold for ambipolar materials for organic electronics and spintronics
Reliability and Validity of the German Version of the AO Spine Patient Reported Outcome Spine Trauma Questionnaire.
Get PDFSTUDY DESIGN
A single-center validation study.
OBJECTIVE
To translate and cross-culturally adapt the AO Spine PROST (Patient Reported Outcome Spine Trauma) into German, and to test its psychometric properties among German-speaking Swiss spine trauma patients.
METHODS
Patients were recruited from a level-1 Swiss trauma center. Next to the AO Spine PROST, the EQ-5D-3L questionnaire was used for concurrent validity. Questionnaires were filled out at two-time points for test-retest reliability. Patient characteristics were analyzed using descriptive statistics. For content validity, floor, and ceiling effects, as well as any irrelevant and missing questions were analyzed. Construct validity of the AO Spine PROST questionnaire to the EQ-5D-3L was tested using Spearman correlation tests.
RESULTS
The AOSpine PROST was translated and adapted into German using established guidelines. We included 179 patients. The floor effect for all items was well within the optimal range (below 15%), while the ceiling effect of seven items was within the optimal range. None of the items displayed a problematic floor or ceiling effect. The overall test-retest reliability of the total PROST score was excellent, with an ICC of .83 (95% CI .69-.91). The Spearman correlation coefficient between the total PROST summary score and EQ-5D-3 L was ρ = .63.
CONCLUSIONS
The German version of the AO Spine PROST questionnaire demonstrated very good validity and reliability results
Global Validation of the AO Spine Upper Cervical Injury Classification: Geographic Region Affects Reliability and Reproducibility.
Get PDFSTUDY DESIGN
Global Survey.
OBJECTIVE
To determine the accuracy, interobserver reliability, and intraobserver reproducibility of the AO Spine Upper Cervical Injury Classification System based on surgeons' AO Spine region of practice (Africa, Asia, Central/South America, Europe, Middle East, and North America).
METHODS
A total of 275 AO Spine members assessed 25 upper cervical spine injuries and classified them according to the AO Spine Upper Cervical Injury Classification System. Reliability, reproducibility, and accuracy scores were obtained over two assessments administered at three-week intervals. Kappa coefficients (ƙ) determined the interobserver reliability and intraobserver reproducibility.
RESULTS
On both assessments, participants from Europe and North America had the highest classification accuracy, while participants from Africa and Central/South America had the lowest accuracy (P < .0001). Participants from Africa (assessment 1 (AS1):ƙ = .487; AS2:0.491), Central/South America (AS1:ƙ = .513; AS2:0.511), and the Middle East (AS1:0.591; AS2: .599) achieved moderate reliability, while participants from North America (AS1:ƙ = .673; AS2:0.648) and Europe (AS1:ƙ = .682; AS2:0.681) achieved substantial reliability. Asian participants obtained substantial reliability on AS1 (ƙ = .632), but moderate reliability on AS2 (ƙ = .566). Although there was a large effect size, the low number of participants in certain regions did not provide adequate certainty that AO regions affected the likelihood of participants having excellent reproducibility (P = .342).
CONCLUSIONS
The AO Spine Upper Cervical Injury Classification System can be applied with high accuracy, interobserver reliability, and intraobserver reproducibility. However, lower classification accuracy and reliability were found in regions of Africa and Central/South America, especially for severe atlas injuries (IIB and IIC) and atypical hangman's type fractures (IIIB injuries)
Development of a new immersive virtual reality (VR) headset-based dexterity training for patients with multiple sclerosis: Clinical and technical aspects.
Get PDFBACKGROUND
Impaired manual dexterity is frequent and disabling in patients with multiple sclerosis (MS), affecting activities of daily living and quality of life.
OBJECTIVE
To develop a new immersive virtual-reality (VR) headset-based dexterity training to improve impaired manual dexterity in persons with MS (pwMS) while being feasible and usable in a home-based setting.
METHODS
The training intervention was tailored to the specific group of pwMS by implementing a simple and intuitive application with regard to hardware and software. To be efficacious, the training intervention covers the main functions of the hands and arm relevant for use in everyday life.
RESULTS
Taking clinical, feasibility, usability as well as technical aspects with regard to hardware and software into account, six different training exercises using hand tracking technology were developed on the Meta quest 2 using Unity.
CONCLUSION
We report the developmental process of a new immersive virtual VR headset-based dexterity training for pwMS implementing clinical and technical aspects. Good feasibility, usability, and patient satisfaction was already shown in a feasibility study qualifying this training intervention for further efficacy trials
Identification and characterization of Hand2 upstream genomic enhancers active in developing stomach and limbs.
No full textBACKGROUND
The bHLH transcription factor HAND2 plays important roles in the development of the embryonic heart, face, limbs, and sympathetic and enteric nervous systems. To define how and when HAND2 regulates these developmental systems, requires understanding the transcriptional regulation of Hand2.
RESULTS
Remarkably, Hand2 is flanked by an extensive upstream gene desert containing a potentially diverse enhancer landscape. Here, we screened the regulatory interval 200 kb proximal to Hand2 for putative enhancers using evolutionary conservation and histone marks in Hand2-expressing tissues. H3K27ac signatures across embryonic tissues pointed to only two putative enhancer regions showing deep sequence conservation. Assessment of the transcriptional enhancer potential of these elements using transgenic reporter lines uncovered distinct in vivo enhancer activities in embryonic stomach and limb mesenchyme, respectively. Activity of the identified stomach enhancer was restricted to the developing antrum and showed expression within the smooth muscle and enteric neurons. Surprisingly, the activity pattern of the limb enhancer did not overlap Hand2 mRNA but consistently yielded a defined subectodermal anterior expression pattern within multiple transgenic lines.
CONCLUSIONS
Together, these results start to uncover the diverse regulatory potential inherent to the Hand2 upstream regulatory interval
Intraoperative in vivo confocal laser endomicroscopy imaging at glioma margins: can we detect tumor infiltration?
No full textOBJECTIVE
Confocal laser endomicroscopy (CLE) is a US Food and Drug Administration-cleared intraoperative real-time fluorescence-based cellular resolution imaging technology that has been shown to image brain tumor histoarchitecture rapidly in vivo during neuro-oncological surgical procedures. An important goal for successful intraoperative implementation is in vivo use at the margins of infiltrating gliomas. However, CLE use at glioma margins has not been well studied.
METHODS
Matching in vivo CLE images and tissue biopsies acquired at glioma margin regions of interest (ROIs) were collected from 2 institutions. All images were reviewed by 4 neuropathologists experienced in CLE. A scoring system based on the pathological features was implemented to score CLE and H&E images from each ROI on a scale from 0 to 5. Based on the H&E scores, all ROIs were divided into a low tumor probability (LTP) group (scores 0-2) and a high tumor probability (HTP) group (scores 3-5). The concordance between CLE and H&E scores regarding tumor probability was determined. The intraclass correlation coefficient (ICC) and diagnostic performance were calculated.
RESULTS
Fifty-six glioma margin ROIs were included for analysis. Interrater reliability of the scoring system was excellent when used for H&E images (ICC [95% CI] 0.91 [0.86-0.94]) and moderate when used for CLE images (ICC [95% CI] 0.69 [0.40-0.83]). The ICCs (95% CIs) of the LTP group (0.68 [0.40-0.83]) and HTP group (0.68 [0.39-0.83]) did not differ significantly. The concordance between CLE and H&E scores was 61.6%. The sensitivity and specificity values of the scoring system were 79% and 37%. The positive predictive value (PPV) and negative predictive value were 65% and 53%, respectively. Concordance, sensitivity, and PPV were greater in the HTP group than in the LTP group. Specificity was higher in the newly diagnosed group than in the recurrent group.
CONCLUSIONS
CLE may detect tumor infiltration at glioma margins. However, it is not currently dependable, especially in scenarios where low probability of tumor infiltration is expected. The proposed scoring system has excellent intrinsic interrater reliability, but its interrater reliability is only moderate when used with CLE images. These results suggest that this technology requires further exploration as a method for consistent actionable intraoperative guidance with high dependability across the range of tumor margin scenarios. Specific-binding and/or tumor-specific fluorophores, a CLE image atlas, and a consensus guideline for image interpretation may help with the translational utility of CLE
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