To characterize the vaginal microbiota of women following preterm premature rupture of membranes (PPROM), and determine if microbiome composition predicts latency duration and perinatal outcomes.
A ...prospective cohort study.
Canada.
Women with PPROM between 24+0 and 33+6 weeks gestational age (GA).
Microbiome profiles, based on pyrosequencing of the cpn60 universal target, were generated from vaginal samples at time of presentation with PPROM, weekly thereafter, and at delivery.
Vaginal microbiome composition, latency duration, gestational age at delivery, perinatal outcomes.
Microbiome profiles were generated from 70 samples from 36 women. Mean GA at PPROM was 28.8 wk (mean latency 2.7 wk). Microbiome profiles were highly diverse but sequences representing Megasphaera type 1 and Prevotella spp. were detected in all vaginal samples. Only 13/70 samples were dominated by Lactobacillus spp. Microbiome profiles at the time of membrane rupture did not cluster by gestational age at PPROM, latency duration, presence of chorioamnionitis or by infant outcomes. Mycoplasma and/or Ureaplasma were detected by PCR in 81% (29/36) of women, and these women had significantly lower GA at delivery and correspondingly lower birth weight infants than Mycoplasma and/or Ureaplasma negative women.
Women with PPROM had mixed, abnormal vaginal microbiota but the microbiome profile at PPROM did not correlate with latency duration. Prevotella spp. and Megasphaera type I were ubiquitous. The presence of Mollicutes in the vaginal microbiome was associated with lower GA at delivery. The microbiome was remarkably unstable during the latency period.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
A large, highly prolific swine farm in Hungary had a 2-year history of neurologic disease among newly weaned (25- to 35-day-old) pigs, with clinical signs of posterior paraplegia and a high mortality ...rate. Affected pigs that were necropsied had encephalomyelitis and neural necrosis. Porcine astrovirus type 3 was identified by reverse transcription PCR and in situ hybridization in brain and spinal cord samples in 6 animals from this farm. Among tissues tested by quantitative RT-PCR, the highest viral loads were detected in brain stem and spinal cord. Similar porcine astrovirus type 3 was also detected in archived brain and spinal cord samples from another 2 geographically distant farms. Viral RNA was predominantly restricted to neurons, particularly in the brain stem, cerebellum (Purkinje cells), and cervical spinal cord. Astrovirus was generally undetectable in feces but present in respiratory samples, indicating a possible respiratory infection. Astrovirus could cause common, neuroinvasive epidemic disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
A unique and highly versatile technique, stress echocardiography (SE) is increasingly recognized for its utility in the evaluation of non-ischaemic heart disease. SE allows for simultaneous ...assessment of myocardial function and haemodynamics under physiological or pharmacological conditions. Due to its diagnostic and prognostic value, SE has become widely implemented to assess various conditions other than ischaemic heart disease. It has thus become essential to establish guidance for its applications and performance in the area of non-ischaemic heart disease. This paper summarizes these recommendations.
T-SPOT.TB assays were performed manually on healthy adolescents during a tuberculosis vaccine trial in Tanzania at 5 intervals over 3 years. Assay results were defined as negative, positive, ...borderline or invalid. Subsequently, microtiter plates were analyzed by an automated reader to obtain quantitative counts of spot forming cells (SFCs) for the present analysis. 3387 T-SPOT.TB samples were analyzed from 928 adolescents; manual and automated assay results were 97% concordant. Based on the quantitative results 143 (15%) participants were prevalent IGRA-positives at baseline, were ineligible for further study. Among the remaining IGRA-negative participants, the annual rate of IGRA conversion was 2·9%. Among 43 IGRA converters with repeat assays 12 (28%) were persistent converters, 16 (37%) were transient converters, and 15 (35%) comprised a new category defined as irregular converters (greater than or equal to2 different subsequent results). ESAT-6 and CFP-10 responses were higher in prevalent than incident positives: 53 vs 36 for CFP-10 (p < 0·007); 44 vs 34 for ESAT-6 (p = 0·12). Definitions of IGRA conversion, reversion, and persistence depend critically on the frequency of testing. Multiple shifts in categories among adolescents in a TB-endemic country may represent multiple infections, variable host responses in subclinical infection, or assay variation. These findings should to be considered in the design and interpretation of TB vaccine trials based on prevention of infection. Household contact studies could determine whether even transient IGRA conversion might represent exposure to an active case of M. tuberculosis disease.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Solitary fibrous tumor is a mesenchymal tumor of fibroblastic type, which can affect any region of the body. Recently, a recurrent gene fusion NAB2-STAT6 has been identified as molecular hallmark. ...The NAB2-STAT6 fusion leads to EGR1 activation and transcriptional deregulation of EGR1-dependent target genes and is a driving event in initiation of SFT. In this study, we report the clinicopathologic and RT-PCR findings and evaluated expression of STAT6 and EGR1 protein in a cohort of 28 SFTs.
28 patients with a median age of 54 years were included with SFTs originating at different sites, most occurring in the lung and pleura (9, 32%), 5 in soft tissues of the lower extremities (18%) and 5 in the head and neck (18%). For detection of the NAB2-STAT6 fusion gene, RT-PCR was performed using RNA extracted from formalin-fixed and paraffin-embedded tissues. Immunohistochemistry was performed on all cases with antibodies against STAT6 and EGR1.
All patients were treated by surgery, 3 with adjuvant chemo- or radiotherapy. Follow-up data of 18 patients could be obtained of which 2 patients died of metastatic disease 13 months and 52 years after first diagnosis. Sixteen patients have no evidence of disease with a median follow up of 29.5 months (range 7 - 120 months). NAB2-STAT6 fusion transcripts were found in 19/28 cases (68%). The most common fusion was between NAB2 exon 4 and STAT6 exon 3 (11/19, 58%), mainly occurring in pleuropulmonary lesions. All cases showed strong nuclear expression of STAT6 (28/28, 100%) while EGR1 showed low-level variable nuclear expression in all samples, comparable with the EGR1 expression results of the control group.
The identification of the NAB2-STAT6 fusion in SFTs can provide important diagnostic information, especially in cases with aberrant morphology or when biopsy material is limited. STAT6 immunohistochemistry is another useful tool in diagnosing SFT. EGR1 immunohistochemistry indicates low-level protein expression in accordance with EGR1 activation due to distorted NAB2 activity.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/13000_2014_224.
Interest surrounding generative large language models (LLMs) has rapidly grown. Although ChatGPT (GPT-3.5), a general LLM, has shown near-passing performance on medical student board examinations, ...the performance of ChatGPT or its successor GPT-4 on specialized examinations and the factors affecting accuracy remain unclear. This study aims to assess the performance of ChatGPT and GPT-4 on a 500-question mock neurosurgical written board examination.
The Self-Assessment Neurosurgery Examinations (SANS) American Board of Neurological Surgery Self-Assessment Examination 1 was used to evaluate ChatGPT and GPT-4. Questions were in single best answer, multiple-choice format. χ 2 , Fisher exact, and univariable logistic regression tests were used to assess performance differences in relation to question characteristics.
ChatGPT (GPT-3.5) and GPT-4 achieved scores of 73.4% (95% CI: 69.3%-77.2%) and 83.4% (95% CI: 79.8%-86.5%), respectively, relative to the user average of 72.8% (95% CI: 68.6%-76.6%). Both LLMs exceeded last year's passing threshold of 69%. Although scores between ChatGPT and question bank users were equivalent ( P = .963), GPT-4 outperformed both (both P < .001). GPT-4 answered every question answered correctly by ChatGPT and 37.6% (50/133) of remaining incorrect questions correctly. Among 12 question categories, GPT-4 significantly outperformed users in each but performed comparably with ChatGPT in 3 (functional, other general, and spine) and outperformed both users and ChatGPT for tumor questions. Increased word count (odds ratio = 0.89 of answering a question correctly per +10 words) and higher-order problem-solving (odds ratio = 0.40, P = .009) were associated with lower accuracy for ChatGPT, but not for GPT-4 (both P > .005). Multimodal input was not available at the time of this study; hence, on questions with image content, ChatGPT and GPT-4 answered 49.5% and 56.8% of questions correctly based on contextual context clues alone.
LLMs achieved passing scores on a mock 500-question neurosurgical written board examination, with GPT-4 significantly outperforming ChatGPT.
A unique and highly versatile technique, stress echocardiography (SE) is increasingly recognized for its utility in the evaluation of non-ischaemic heart disease. SE allows for simultaneous ...assessment of myocardial function and haemodynamics under physiological or pharmacological conditions. Due to its diagnostic and prognostic value, SE has become widely implemented to assess various conditions other than ischaemic heart disease. It has thus become essential to establish guidance for its applications and performance in the area of non-ischaemic heart disease. This paper summarizes these recommendations.
Fabry disease is an X-linked progressive multisystemic genetic sphingolipidosis caused by deficient activity of lysosomal α-galactosidase A. Men aged>30 years and women aged>40 years most often ...present with unexplained left ventricular hypertrophy, usually concentric and non-obstructive, but sometimes mimicking sarcomeric hypertrophic cardiomyopathy, particularly when isolated, as in the cardiac or late-onset variant of the disease. In hypertrophic cardiomyopathy cohorts, up to 1% of patients have been diagnosed with Fabry disease. Frequent cardiac symptoms include chronotropic incompetence, severe conduction disturbances and arrhythmias, heart failure and sudden death, and cardiovascular complications are currently the leading cause of death at a mean age of 55 years in men and 66 years in women. Complementary to screening for extracardiac manifestations, the initial cardiac evaluation should include long-duration electrocardiogram recordings, echocardiography and late gadolinium and T1 mapping magnetic resonance imaging. Abnormalities of a non-hypertrophied inferolateral wall at the base of the left ventricle (thinning, decreased strain, midwall fibrosis) and low native T1 signal on magnetic resonance imaging are evocative. Aggressive cardiac management may include the control of cardiovascular risk factors, anticoagulation, permanent cardiac pacing and/or an implantable cardioverter defibrillator device, while antiarrhythmics and beta-blockers should be used with caution. Specific therapy should be initiated at the earliest stage, when the first structural or functional cardiac abnormalities are detected, and should include enzyme replacement therapy (available since 2001) or chaperone therapy (available since 2016) (the use of which is limited to patients with Fabry disease and an amenable α-galactosidase A GLA gene mutation).
La maladie de Fabry est une sphingolipidose lysosomale de transmission génétique liée au chromosome X, entraînant un déficit d’activité de l’α-galactosidase A lysosomale. Les hommes atteints de plus de 30 ans et les femmes de plus de 40 ans présentent souvent une hypertrophie ventriculaire gauche, habituellement concentrique et non-obstructive, mais qui peut mimer une cardiomyopathie hypertrophique (CMH) sarcomérique, particulièrement lorsqu’isolée comme dans le cas du variant cardiaque de l’affection. La maladie de Fabry est cause de 0,7–1 % des CMH en milieu cardiologique. Les symptômes cardiaques, fréquents, incluent incompétence chronotrope, anomalies sévères de conduction, arythmies, insuffisance cardiaque et mort subite. Les complications cardiovasculaires représentent désormais la cause la plus fréquente de décès à un âge moyen de 55 ans chez l’homme et 66 ans chez la femme. Associée au dépistage des atteintes extracardiaques, l’évaluation cardiaque initiale inclut enregistrements holter ECG longue durée, échocardiographie et imagerie cardiaque par résonnance magnétique (IRM) avec injection de gadolinium. Les anomalies du segment ventriculaire gauche basal inférolatéral (amincissement, strain diminué, fibrose médio-murale) sont évocatrices, comme un signal T1 altéré en IRM. La thérapeutique cardiovasculaire doit être agressive et associe potentiellement contrôle des facteurs de risque, anticoagulation, implantation de pacemaker et/ou défibrillateur, alors que amiodarone et bêtabloquants devraient être considérés avec prudence. Les traitements spécifiques devraient être initiées tôt, dès la détection des premières anomalies cardiaques structurelles ou fonctionnelles, et incluent le traitement enzymatique substitutif et une molécule chaperonne (réservée uniquement aux patients porteurs d’une mutation sensible du gène GLA).
This study compared lead (Pb) immobilization efficacies in mining/smelting impacted soil using phosphate and iron amendments via ingestion and inhalation pathways using in vitro and in vivo assays, ...in conjunction with investigating the dynamics of dust particles in the lungs and gastro-intestinal tract via X-ray fluorescence (XRF) microscopy. Phosphate amendments phosphoric acid (PA), hydroxyapatite, monoammonium phosphate (MAP), triple super phosphate (TSP), and bone meal biochar and hematite were applied at a molar ratio of Pb:Fe/P = 1:5. Pb phosphate formation was investigated in the soil/post-in vitro bioaccessibility (IVBA) residuals and in mouse lung via extended X-ray absorption fine structure (EXAFS) and X-ray absorption near edge structures (XANES) spectroscopy, respectively. EXAFS analysis revealed that anglesite was the dominant phase in the ingestible (<250 μm) and inhalable (<10 μm) particle fractions. Pb IVBA was significantly reduced (p < 0.05) by phosphate amendments in the <250 μm fraction (solubility bioaccessibility research consortium assay) and by PA, MAP, and TSP in the <10 μm fraction (inhalation–ingestion bioaccessibility assay). A 21.1% reduction in Pb RBA (<250 μm fraction) and 56.4% reduction in blood Pb concentration (<10 μm fraction) were observed via the ingestion and inhalation pathways, respectively. XRF microscopy detected Pb in the stomach within 4 h, presumably via mucociliary clearance.
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