Effectiveness of a Balanced Nine-Strain Synbiotic in Primary-Care Irritable Bowel Syndrome Patients—A Multi-Center, Randomized, Double-Blind, Placebo-Controlled Trial

The aim of the study was to characterize effects of a multi-strain synbiotic in patients with moderate to severe irritable bowel syndrome (IBS) of all stool form types. A total of 202 adult IBS patients were randomized (1:1) and after a four-week treatment-free run-in phase and were treated either with the synbiotic or a placebo for 12 weeks. The primary endpoints were the assessment of the severity of IBS symptoms (IBS-SSS) and the improvement of IBS global symptoms (IBS-GIS). Secondary endpoints comprised adequate relief (IBS-AR scale), stool form type (Bristol Stool Form Scale), bowel movements, severity of abdominal pain and bloating, stool pressure, feeling of incomplete stool evacuation, and adverse events. A total of 201 patients completed the study. Synbiotic treatment, in comparison to placebo, significantly improved IBS-SSS and IBS-GIS scores. At the end of the treatment, 70% of patients in the synbiotic group achieved adequate relief. After 12 weeks of treatment, the secondary endpoints were favorably differentiated in the synbiotic group when compared with the placebo group. Two patients in the synbiotic group reported transient adverse events (headache). The results indicate that treatment of IBS patients with the synbiotic significantly improved all major symptoms of IBS and was well-tolerated. The ClinicalTrials.gov registration was NCT05731232

New generation of oxide-based nanoparticles for the applications in early cancer detection and diagnostics

Hereby the possible applications of oxide nanoparticles in the cancer diagnostics and therapy are presented. Cancer diseases are nowadays one of the most common causes of death in the highly-developed countries. Discussed will be the current clinical cancer detection methods with their shortcomings. The role of nanomedicine in cancer medicine and the potential applications of nanoparticles debated in the literature will be critically evaluated. In the second part, the most common methods for the nanoparticle synthesis will be discussed. Finally, the system for cancer detection based on the enhanced permeation-retention of multimodal high-k oxide nanoparticles doped with lanthanides will be proposed for both for themagnetic resonance imaging (non-gadolinium contrast agents) and for fluorescence guided biopsy and surgery

Dual-Wavelength Pumped Highly Birefringent Microstructured Silica Fiber for Widely Tunable Soliton Self-Frequency Shift

We report the design of a microstructured silica-based fiber for widely tunable soliton self-frequency shift, suitable for pumping with two most common fiber laser wavelengths: 1.04 {\mu}m and 1.55 {\mu}m. Depending on the pump source, the output spectrum can be continuously tuned up to 1.67 {\mu}m (pump at 1.04 {\mu}m) or 1.95 {\mu}m (pump at 1.55 {\mu}m) in the same 1.5 m-long fiber sample, with pump-to-soliton conversion efficiency higher than 20%. The fiber is highly birefringent, which results in an excellent polarization extinction ratio of the soliton, reaching 26 dB. The shifted solitons have a high degree of coherence confirmed by pulse-to-pulse interference measurement. The available soliton tuning range covers the wavelengths inaccessible for fiber lasers, e.g., 1.3 {\mu}m and 1.7 {\mu}m, highly important for multi-photon microscopy and imaging. Our work shows that it is possible to design and fabricate one universal optical fiber that supports soliton shift when pumped at two different wavelengths separated by over 500 nm

High prevalence of somatic PIK3CA and TP53 pathogenic variants in the normal mammary gland tissue of sporadic breast cancer patients revealed by duplex sequencing

The mammary gland undergoes hormonally stimulated cycles of proliferation, lactation, and involution. We hypothesized that these factors increase the mutational burden in glandular tissue and may explain high cancer incidence rate in the general population, and recurrent disease. Hence, we investigated the DNA sequence variants in the normal mammary gland, tumor, and peripheral blood from 52 reportedly sporadic breast cancer patients. Targeted resequencing of 542 cancer-associated genes revealed subclonal somatic pathogenic variants of: PIK3CA, TP53, AKT1, MAP3K1, CDH1, R81, NCOR1, MED12, CBFB, T8X3, and TSHR in the normal mammary gland at considerable allelic frequencies (9 x 10(-2) - 5.2 x 10(-1)), indicating clonal expansion. Further evaluation of the frequently damaged PIK3CA and TP53 genes by ultra-sensitive duplex sequencing demonstrated a diversified picture of multiple low-level subclonal (in 10(-2)-10(-4) alleles) hotspot pathogenic variants. Our results raise a question about the oncogenic potential in non-tumorous mammary gland tissue of breast-conserving surgery patients

Outcomes in Newly Diagnosed Atrial Fibrillation and History of Acute Coronary Syndromes: Insights from GARFIELD-AF

BACKGROUND: Many patients with atrial fibrillation have concomitant coronary artery disease with or without acute coronary syndromes and are in need of additional antithrombotic therapy. There are few data on the long-term clinical outcome of atrial fibrillation patients with a history of acute coronary syndrome. This is a 2-year study of atrial fibrillation patients with or without a history of acute coronary syndromes

Analysis of Outcomes in Ischemic vs Nonischemic Cardiomyopathy in Patients With Atrial Fibrillation A Report From the GARFIELD-AF Registry

IMPORTANCE Congestive heart failure (CHF) is commonly associated with nonvalvular atrial fibrillation (AF), and their combination may affect treatment strategies and outcomes