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Chronic pericarditis and recurrent pericardial effusion of unknown origin in a kitten: a case report.
Get PDFA 3-month-old kitten was presented after successful cardiopulmonary resuscitation, including a presumed intracardial injection by its primary care veterinarian. Throughout the subsequent hospitalization in the intensive care unit, the cat exhibited recurrent hemorrhagic pericardial effusions, along with concurrent pleural and abdominal effusions, resulting in multiple clinical deteriorations, necessitating pericardiocentesis and thoracocentesis. Despite more than 3 days of intensive care, the cat experienced another cardiopulmonary arrest with unsuccessful attempts to achieve the return of spontaneous circulation. Necropsy and histopathological findings revealed diffuse chronic-active pericarditis and hemorrhagic pericardial effusion, a condition that has not been documented in the context of cardiopulmonary resuscitation or pericardiocentesis
Efficient characterization of multiple binding sites of small molecule imaging ligands on amyloid-beta, tau and alpha-synuclein.
Get PDFPURPOSE
There is an unmet need for compounds to detect fibrillar forms of alpha-synuclein (αSyn) and 4-repeat tau, which are critical in many neurodegenerative diseases. Here, we aim to develop an efficient surface plasmon resonance (SPR)-based assay to facilitate the characterization of small molecules that can bind these fibrils.
METHODS
SPR measurements were conducted to characterize the binding properties of fluorescent ligands/compounds toward recombinant amyloid-beta (Aβ)42, K18-tau, full-length 2N4R-tau and αSyn fibrils. In silico modeling was performed to examine the binding pockets of ligands on αSyn fibrils. Immunofluorescence staining of postmortem brain tissue slices from Parkinson's disease patients and mouse models was performed with fluorescence ligands and specific antibodies.
RESULTS
We optimized the protocol for the immobilization of Aβ42, K18-tau, full-length 2N4R-tau and αSyn fibrils in a controlled aggregation state on SPR-sensor chips and for assessing their binding to ligands. The SPR results from the analysis of binding kinetics suggested the presence of at least two binding sites for all fibrils, including luminescent conjugated oligothiophenes, benzothiazole derivatives, nonfluorescent methylene blue and lansoprazole. In silico modeling studies for αSyn (6H6B) revealed four binding sites with a preference for one site on the surface. Immunofluorescence staining validated the detection of pS129-αSyn positivity in the brains of Parkinson's disease patients and αSyn preformed-fibril injected mice, 6E10-positive Aβ in arcAβ mice, and AT-8/AT-100-positivity in pR5 mice.
CONCLUSION
SPR measurements of small molecules binding to Aβ42, K18/full-length 2N4R-tau and αSyn fibrils suggested the existence of multiple binding sites. This approach may provide efficient characterization of compounds for neurodegenerative disease-relevant proteinopathies
In vitro evaluation of the impact of intraoral scanner, scanning aids, and the scanned arch on the scan accuracy of edentulous arches.
Get PDFPURPOSE
To assess the accuracy of complete maxillary and mandibular edentulous arch scans obtained using two different intraoral scanners (IOSs), with and without scanning aids, and to compare these results to those obtained using conventional impression methods.
MATERIALS AND METHODS
Two IOSs were used (TRIOS 4 [TRI] and Emerald S [EMR]) to scan maxillary and mandibular typodonts. The typodonts were scanned without scanning aids [TRI_WSA and EMR_WSA groups] (n = 10). The typodonts were then scanned under four scanning aid conditions (n = 10): composite markers [TRI_MRK and EMR_MRK groups], scanning spray [TRI_SPR and EMR_SPR groups], pressure indicating paste [TRI_PIP and EMR_PIP groups], and liquid-type scanning aid [TRI_LQD and EMR_LQD groups]. Conventional impressions of both arches were also made using irreversible hydrocolloids in stock trays [IHC] and using polyvinyl siloxane (PVS) impression material in custom trays (n = 10) which were digitized using a laboratory scanner. Using a metrology software program, all scans were compared to a reference scan in order to assess trueness and to each other to assess precision. Trueness and precision were expressed as the root mean square (RMS) of the absolute deviation values and the statistical analysis was modeled on a logarithmic scale using fixed-effects models to meet model assumptions (α = 0.05).
RESULTS
The main effect of arch (p = 0.004), scanner (p < 0.001), scanning aid (p = 0.041), and the interaction between scanner and scanning aid (p = 0.027) had a significant effect on mean RMS values of trueness. The arch (p = 0.015) and scanner (p < 0.001) had a significant effect on the mean RMS values of precision. The maxillary arch had better accuracy compared to the mandible. The TRIOS 4 scanner had better accuracy than both the Emerald S scanner and conventional impressions. The Emerald S had better precision than conventional impressions. The scanning spray and liquid-type scanning aids produced the best trueness with the TRIOS 4 scanner, while the liquid-type scanning aid and composite markers produced the best trueness for the Emerald S scanner.
CONCLUSION
The scanned arch and the type of scanner had a significant effect on the accuracy of digital scans of completely edentulous arches. The scanning aid had a significant effect on the trueness of digital scans of completely edentulous arches which varied depending on the scanner used
The Brief Symptom Inventory in the Swiss general population: Presentation of norm scores and predictors of psychological distress.
Get PDFPsychological distress is an important and frequent health problem. The Brief Symptom Inventory (BSI) allows screening for psychological distress in clinical, general and research populations. We aimed to provide normative data for the BSI and the BSI-18 for the Swiss general population: We 1) present psychometric properties, 2) develop a Swiss T-standardization and validate it using a clinical sample, 3) describe psychological distress in the Swiss general population and the clinical sample, and 4) compare the means and T-standardized scores of the Swiss general population to different German norm populations. Using a cross-sectional study design, we invited a representative sample of the Swiss general population aged 18-75 years to the study. A sample of psychotherapy outpatients had competed the BSI before start of their therapy. We calculated scores for the nine scales of the BSI (three of them constitute the BSI-18), the T-standardization and the following BSI indices: Global Severity Index (GSI), Positive Symptom Total (PST), Positive Symptom Distress Index (PSDI), and Caseness (reaching T≥63 on the GSI or T≥63 on at least two of the scales). A total of 1238 general population participants completed the BSI (41.8% male; mean age 48.9 years). The BSI had good psychometric properties. The Swiss T-standardization showed good validity when applied in the clinical sample. Females reached a significantly higher GSI score than males (p<0.001). Older participants (p = 0.026), those with higher education (p <0.001), and those employed or retired (p<0.001) reached lower scores than participants aged 18-25 years, those with compulsory schooling, and unemployed participants, respectively. A total of 18.1% (CI: 16.0-20.5) participants of the general population and 75.2% (CI: 73.7-76.7) of the psychotherapy patients were considered cases with psychological distress. Our study presents detailed normative data for the BSI and the BSI-18 based on a representative sample of the Swiss general population. This information will be helpful for clinical applications and research in the Swiss and international context
Termination of Resuscitation Rules and Survival Among Patients With Out-of-Hospital Cardiac Arrest: A Systematic Review and Meta-Analysis.
Get PDFIMPORTANCE
Termination of resuscitation (TOR) rules may help guide prehospital decisions to stop resuscitation, with potential effects on patient outcomes and health resource use. Rules with high sensitivity risk increasing inappropriate transport of nonsurvivors, while rules without excellent specificity risk missed survivors. Further examination of the performance of TOR rules in estimating survival of out-of-hospital cardiac arrest (OHCA) is needed.
OBJECTIVE
To determine whether TOR rules can accurately identify patients who will not survive an OHCA.
DATA SOURCES
For this systematic review and meta-analysis, the MEDLINE, Embase, CINAHL, Cochrane Library, and Web of Science databases were searched from database inception up to January 11, 2024. There were no restrictions on language, publication date, or time frame of the study.
STUDY SELECTION
Two reviewers independently screened records, first by title and abstract and then by full text. Randomized clinical trials, case-control studies, cohort studies, cross-sectional studies, retrospective analyses, and modeling studies were included. Systematic reviews and meta-analyses were reviewed to identify primary studies. Studies predicting outcomes other than death, in-hospital studies, animal studies, and non-peer-reviewed studies were excluded.
DATA EXTRACTION AND SYNTHESIS
Data were extracted by one reviewer and checked by a second. Two reviewers assessed risk of bias using the Revised Quality Assessment Tool for Diagnostic Accuracy Studies. Cochrane Screening and Diagnostic Tests Methods Group recommendations were followed when conducting a bivariate random-effects meta-analysis. This review followed the Preferred Reporting Items for a Systematic Review and Meta-Analysis of Diagnostic Test Accuracy Studies (PRISMA-DTA) statement and is registered with the International Prospective Register of Systematic Reviews (CRD42019131010).
MAIN OUTCOMES AND MEASURES
Sensitivity and specificity tables with 95% CIs and bivariate summary receiver operating characteristic (SROC) curves were produced. Estimates of effects at different prevalence levels were calculated. These estimates were used to evaluate the practical implications of TOR rule use at different prevalence levels.
RESULTS
This review included 43 nonrandomized studies published between 1993 and 2023, addressing 29 TOR rules and involving 1 125 587 cases. Fifteen studies reported the derivation of 20 TOR rules. Thirty-three studies reported external data validations of 17 TOR rules. Seven TOR rules had data to facilitate meta-analysis. One clinical study was identified. The universal termination of resuscitation rule had the best performance, with pooled sensitivity of 0.62 (95% CI, 0.54-0.71), pooled specificity of 0.88 (95% CI, 0.82-0.94), and a diagnostic odds ratio of 20.45 (95% CI, 13.15-31.83).
CONCLUSIONS AND RELEVANCE
In this review, there was insufficient robust evidence to support widespread implementation of TOR rules in clinical practice. These findings suggest that adoption of TOR rules may lead to missed survivors and increased resource utilization
First iteration of a User-Centered Design process to develop an in-bed leg press.
No full textBACKGROUND
Physical inactivity is prevalent among hospitalized patients and the daytime spent lying should be utilised for exercise. However, implementing new interventions in hospitals' complex daily routines is difficult and requires a participatory approach.
OBJECTIVE
Exploring clinical settings and clinicians' perspectives regarding exercise in hospitalized patients to gauge the potential of further development of an in-bed training device and to formulate development goals.
METHODS
A User-Centered Design approach was employed, consisting of work shadowing and focus groups with physiotherapists and nurses. Content and network analyses of the focus group data were performed. Personas were then developed and used to create clinical scenarios.
RESULTS
Some clinicians perceived in-bed exercise counterproductive, while others recognized potential for unsupervised training. The most important design characteristics appeared to be a small size, low weight and simplicity of use to facilitate storage, transportation, and administration, respectively. The scenarios revealed that the device's use could increase the physical activity time by 1.4%, although it would also increase the working time of clinicians.
CONCLUSION
The study highlighted the difficulties in developing a usable training device but encouraged the authors to pursue their efforts under the strict condition of following the formulated development goals
Induced Periodontitis in Rats With Three Ligature Types: An Exploratory Study.
Get PDFBACKGROUND
The placement of ligatures in the cervical area of rat molars is considered as a predictable model to induce periodontitis.
OBJECTIVES
The present explorative study aimed to compare the efficacy of metal wires (MWs), without or with sandblasting, versus silk ligatures (SLs) in inducing periodontal bone loss in rats.
MATERIALS AND METHODS
Twenty-four Wistar rats were randomly divided into three groups of eight rats that received three different types of ligatures (MW, sandblasted wire [SMW], and SL) around their first right mandibular molar, while the contralateral tooth was left without the ligature and served as a control. Bone loss was assessed by measuring the distance from the cementoenamel junction (CEJ) to the bone crest at the distal aspect of the first molar on central mesiodistal sections generated from micro-CT scans taken 24 and 35 days after ligature placement.
RESULTS
In the SL group, only in two rats the ligatures were retained until the end of the 24-day period; in all other animals, the ligatures were lost at some time point. In the SMW, the ligatures were retained only for the 24-day period. In the MW group, no ligatures were lost. Irrespective of the group or experimental period, the difference in the crestal bone level between ligated and control teeth was in most cases z < 0.20 mm, that is, in 19 out of 25 pairs of teeth. In a few cases, the bone crest was more apically located at the control teeth compared to the ligated ones (four cases each, during both 24- and 35-day experimental periods).
CONCLUSIONS
Bone loss was minimal during the experimental period, with no significant differences between the test and control teeth, or among the three types of ligatures. MWs, not even roughened, do not seem to be a better alternative to SLs for inducing bone loss in the experimental periodontitis model in the rat. This assumption, however, has to be confirmed in a larger, well-powered study
Outcome of gastric electrical stimulator with and without pyloromyotomy for refractory gastroparesis.
Get PDFBACKGROUND
Surgical treatments of refractory gastroparesis include pyloromyotomy and gastric electrical stimulator (GES). It is unclear if patients may benefit from a combined approach with concomitant GES and pyloromyotomy.
METHODS
Retrospective cohort analysis of all patients with refractory gastroparesis treated with GES implantation with and without concomitant pyloromyotomy at Cleveland Clinic Florida from January 2003 to January 2023. Primary endpoint was efficacy (clinical response duration and success rate) and secondary endpoints included safety (postoperative morbidity) and length of stay. Success rate was defined as the absence of one of the following reinterventions during follow-up: Roux-en-Y gastric bypass (RYGB), pyloromyotomy, GES removal.
RESULTS
During a period of 20 years, 134 patients were treated with GES implantation. Three patients with history of previous surgical pyloromyotomy or RYGB were excluded from the analysis. Median follow-up was 31 months (IQR 10, 72). Forty patients (30.5%) had GES with pyloromyotomy, whereas 91 (69.5%) did not have pyloromyotomy. Most of the patients had idiopathic (n = 68, 51.9%) or diabetic (n = 58, 43.3%) gastroparesis. Except for preoperative use of opioids (47.5 vs 14.3%; p < 0.001), patient's characteristics were similar in both groups. There were no significant differences between the two groups in terms of overall postoperative complications (17.5% vs 14.3%; p = 0.610), major postoperative complications (0% vs 2.2%; p = 1), and length of stay (2(IQR 1, 2) vs 2(IQR 1, 3) days; p = 0.068). At 5 years, success rate was higher in patients with than without pyloromyotomy however not statistically significant (82% versus 62%, p = 0.066). Especially patients with diabetic gastroparesis seemed to benefit from pyloromyotomy during GES (100% versus 67%, p = 0.053). In an adjusted Cox regression, GES implantation without pyloromyotomy was associated with a 2.66 times higher risk of treatment failure compared to GES implantation with pyloromyotomy (HR 2.66, 95% CI 1.03-6.94, p = 0.044).
CONCLUSION
Pyloromyotomy during GES implantation for gastroparesis seems to be associated with a longer clinical response with similar postoperative morbidity and length of hospital stay than GES without pyloromyotomy. Patient with diabetic gastroparesis might benefit from a combination of GES implantation and pyloromyotomy
Efficacy of a transdiagnostic Internet prevention approach in adolescents (EMPATIA study): study protocol of a randomized controlled trial.
Get PDFBACKGROUND
Most mental disorders have their onset in adolescence. Preventive interventions during this period are important; however, help-seeking behavior is generally poor in this age group resulting in low treatment rates. Internet interventions are expected to be an effective, low-threshold, and scalable approach to overcome barriers to help-seeking, particularly for individuals experiencing subclinical symptoms. Internet-delivered indicated prevention seems promising as it targets individuals with minimal symptoms of mental disorders who might need care but are not help-seeking yet. Previous indicated prevention-approaches have mainly targeted specific risk-syndromes. However, this contradicts the increasing recognition of emerging psychopathology as a complex system characterized by co-occurrence and rapid shifts of subclinical symptoms cutting across diagnostic categories. Therefore, this study will investigate the efficacy, mediators, moderators, and core symptomatic changes of a transdiagnostic Internet-delivered indicated prevention program (EMPATIA program) for adolescents.
METHODS
This randomized controlled trial (RCT) will be conducted in a general population sample (planned n = 152) of adolescents aged 12-18 years with subclinical symptoms but without any current or past mental disorder. Participants will be randomly assigned to the EMPATIA program or a care as usual (CAU) control condition. The 8-week guided EMPATIA program encompasses 8 modules targeting the following transdiagnostic mechanisms: repetitive negative thinking, self-perfectionism, emotion regulation, intolerance of uncertainty, rejection sensitivity, and behavioral avoidance. Participants will be asked to answer online self-report questionnaires at baseline, after 8 weeks, and at 6-, 9-, and 12-month follow-up. Diagnostic telephone interviews will be conducted at baseline and at 12-month follow-up. Additionally, intervention-specific constructs (motivation, alliance, negative effects, satisfaction, adherence) will be assessed during and after the EMPATIA program. The level of self-reported general psychopathology post-intervention is the primary outcome.
DISCUSSION
Results will be discussed considering the potential of Internet interventions as a scalable, low-threshold option for indicated prevention in adolescents experiencing subclinical symptoms. The EMPATIA program introduces a novel Internet prevention program targeting six transdiagnostic mechanisms associated with various mental health outcomes. Thereby, this trial pursues a very timely and important topic because it may contribute to narrow the current care gap for adolescents, to prevent mental health problems and related negative consequences, and to promote mental health in the long-term.
TRIAL REGISTRATION
The trial was approved by Swissmedic (Registration Number: 10001035, 08/22/2022) and the Ethics Committee of Bern (Registration Number: 2022-D0036, 08/22/2022). The trial was registered at ClinicalTrials.gov NCT05934019 on 07-03-2023
Globoside Is an Essential Intracellular Factor Required for Parvovirus B19 Endosomal Escape.
Get PDFHuman parvovirus B19 (B19V), like most parvoviruses, possesses phospholipase A2 (PLA2) activity, which is thought to mediate endosomal escape by membrane disruption. Here, we challenge this model and find evidence for a mechanism of B19V entry mediated by the glycosphingolipid globoside without endosome disruption and retrograde transport to the Golgi. We show that B19V PLA2 activity requires specific calcium levels and pH conditions that are not optimal in endosomes. Accordingly, endosomal membrane integrity was maintained during B19V entry. Furthermore, endosomes remained intact when loaded with MS2 bacteriophage particles pseudotyped with multiple B19V PLA2 subunits, providing superior enzymatic potential compared to native B19V. In globoside knockout cells, incoming viruses are arrested in the endosomal compartment and the infection is blocked. Infection can be rescued by promoting endosomal leakage with polyethyleneimine (PEI), demonstrating the essential role of globoside in facilitating endosomal escape. Incoming virus colocalizes with Golgi markers and interfering with Golgi function blocks infection, suggesting that globoside-mediated entry involves the Golgi compartment, which provides conditions favorable for the lipolytic PLA2. Our study challenges the current model of B19V entry and identifies globoside as an essential intracellular receptor required for endosomal escape
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