HF Etiology and cardiac contractility modulation therapy.

OBJECTIVES: Our study aimed to assess the safety and efficacy of cardiac contractility modulation (CCM) therapy in patients with heart failure with reduced ejection fraction (HFrEF) depending on HF etiology. METHODS: We enrolled 166 patients with optimal medical therapy-resistant HFrEF (median age 59 years, 83.7% males, median NYHA class - 2, median left ventricular ejection fraction (LVEF) - 29.0%) who underwent CCM therapy device implantation from 2013 to 2019 in four medical centers in Russia. The HF etiology was determined based on invasive coronary angiography or cardiac MRI data. Transthoracic echocardiography (TTE), 6-minute walking test (6MWT), and NTproBNP-tests were performed at a baseline and 12 months after the implantation. RESULTS: The ischemic etiology of HF was revealed in 100 patients (61.5%) (ICM group); the non-ischemic group (NICM) evolved 66 patients (38.5%). Patients in the ICM group were significantly older (61[57-69] vs. 55 [42.8-61], p < 0.001), more frequently had hypertension (79% vs. 42.4%, p < 0.001) and chronic kidney disease (43% vs. 22.7%, p = 0.012). Patients in the NICM group had significantly more often atrial fibrillation (AF) (58% vs. 74%, p = 0.048), larger end-diastolic volume (EDV) (249 [208-309] vs. 220 [192-271], p = 0.019) and end-systolic volume (ESV) (183 [147-230] vs. 154 [128-199], p = 0.003). There were no significant differences in mortality between ICM and NICM groups (14.4 vs. 10.8%, p = 0.51). In 12 months, there was a significant increase in LVEF in the NICM group (+ 2.0 [2-6] vs. +7.7 [2-12], p < 0.001), while the improvement in the 6MWT (+ 75 [22-108] vs. +80 [10-160], p = 0.851) and NYHA class did not reach the level of significance. The subanalysis between patients with improved NYHA class and those without improvement revealed that patients without improvement more frequently had AF (56% vs. 89%; p < 0.01), chronic obstructive lung disease (18% vs. 35% p = 0.047), higher blood pressure (110 [105-120] vs. 120[110-129]; p = 0.032). CONCLUSION: In this multicenter retrospective study, patients with non-ischemic HFrEF showed a significantly higher improvement in LVEF and LV reverse remodeling following CCM therapy device implantation. There was no significant association between HF etiology and survival in drug-resistant HFrEF patients following CCM therapy.

Multi-Wavelength Raman Differentiation of Malignant Skin Neoplasms.

Raman microspectroscopy has become an effective method for analyzing the molecular appearance of biomarkers in skin tissue. For the first time, we acquired in vitro Raman spectra of healthy and malignant skin tissues, including basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), at 532 and 785 nm laser excitation wavelengths in the wavenumber ranges of 900-1800 cm-1 and 2800-3100 cm-1 and analyzed them to find spectral features for differentiation between the three classes of the samples. The intensity ratios of the bands at 1268, 1336, and 1445 cm-1 appeared to be the most reliable criteria for the three-class differentiation at 532 nm excitation, whereas the bands from the higher wavenumber region (2850, 2880, and 2930 cm-1) were a robust measure of the increased protein/lipid ratio in the tumors at both excitation wavelengths. Selecting ratios of the three bands from the merged (532 + 785) dataset made it possible to increase the accuracy to 87% for the three classes and reach the specificities for BCC + SCC equal to 87% and 81% for the sensitivities of 95% and 99%, respectively. Development of multi-wavelength excitation Raman spectroscopic techniques provides a versatile non-invasive tool for research of the processes in malignant skin tumors, as well as other forms of cancer.

Impact of Gut Microbiota and SCFAs in the Pathogenesis of PCOS and the Effect of Metformin Therapy.

Polycystic ovary syndrome (PCOS) is a complex disorder that impacts both the endocrine and metabolic systems, often resulting in infertility, obesity, insulin resistance, and cardiovascular complications. The aim of this study is to investigate the role of intestinal flora and its metabolites, particularly short-chain fatty acids (SCFAs), in the development of PCOS, and to assess the effects of metformin therapy on these components. SCFA levels in fecal and blood samples from women with PCOS (n=69) and healthy controls (n=18) were analyzed using Gas Chromatography-Mass Spectrometry (GC/MS) for precise measurement. Fecal microbiota were quantitatively detected by real-time polymerase chain reaction (PCR). To assess the efficacy of six months of metformin treatment, changes in the microbiota and SCFAs in the PCOS group (n=69) were also evaluated. The results revealed that women with PCOS exhibited a significant reduction in beneficial bacteria (namely, the C. leptum group and Prevotella spp.) alongside a notable overgrowth of opportunistic microorganisms (C. perfringens, C. difficile, Staphylococcus spp., and Streptococcus spp.). An overproduction of acetic acid (AA, FC=0.47, p<0.05) and valeric acid (VA, FC=0.54, p<0.05) suggests a link between elevated SCFAs and the development of obesity and PCOS. Interestingly, AA in the bloodstream might offer a protective effect against PCOS by ameliorating key symptoms such as high body mass index (r=-0.33, p=0.02), insulin resistance (r=-0.39, p=0.02), and chronic inflammation. Although serum SCFA levels showed non-significant changes following metformin treatment (p>0.05), the normalization of AA in the gut underscores that metformin exerts a more pronounced effect locally within the gastrointestinal tract. Furthermore, the study identified the most effective model for predicting the success of metformin therapy, based on serum concentrations of butyric acid (BA) and VA, achieving a 91% accuracy rate, 100% sensitivity, and 80% specificity. These promising findings highlight the potential for developing targeted interventions and personalized treatments, ultimately improving clinical outcomes for women with PCOS.

Multispectral Raman Differentiation of Malignant Skin Neoplasms In Vitro: Search for Specific Biomarkers and Optimal Wavelengths.

Confocal scanning Raman and photoluminescence (PL) microspectroscopy is a structure-sensitive optical method that allows the non-invasive analysis of biomarkers in the skin tissue. We used it to perform in vitro diagnostics of different malignant skin neoplasms at several excitation wavelengths (532, 785 and 1064 nm). Distinct spectral differences were noticed in the Raman spectra of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), compared with healthy skin. Our analysis of Raman/PL spectra at the different excitation wavelengths enabled us to propose two novel wavelength-independent spectral criteria (intensity ratios for 1302 cm-1 and 1445 cm-1 bands, 1745 cm-1 and 1445 cm-1 bands), related to the different vibrational "fingerprints" of cell membrane lipids as biomarkers, which was confirmed by the multivariate curve resolution (MCR) technique. These criteria allowed us to differentiate healthy skin from BCC and SCC with sensitivity and specificity higher than 95%, demonstrating high clinical importance in the differential diagnostics of skin tumors.

Nanoscale Vacancy-Mediated Aggregation, Dissociation, and Splitting of Nitrogen Centers in Natural Diamond Excited by Visible-Range Femtosecond Laser Pulses.

Natural IaA+B diamonds were exposed in their bulk by multiple 0.3 ps, 515 nm laser pulses focused by a 0.25 NA micro-objective, producing in the prefocal region (depth of 20-50 µm) a bulk array of photoluminescent nanostructured microtracks at variable laser exposures and pulse energies. These micromarks were characterized at room (25°) and liquid nitrogen cooling (-120 °C) temperatures through stationary 3D scanning confocal photoluminescence (PL) microspectroscopy at 405 and 532 nm excitation wavelengths. The acquired PL spectra exhibit a linearly increasing pulse-energy-dependent yield in the range of 575 to 750 nm (NV0, NV- centers) at the expense of the simultaneous reductions in the blue-green (450-570 nm; N3a, H4, and H3 centers) and near-IR (741 nm; V0 center) PL yield. A detailed analysis indicates a low-energy rise in PL intensity for B2-related N3a, H4, and H3 centers, while at higher, above-threshold pulse energies it decreases for the H4, H3, and N3a centers, converting into NV centers, with the laser exposure effect demonstrating the same trend. The intrinsic and (especially) photo-generated vacancies were considered to drive their attachment as separate species to nitrogen centers at lower vacancy concentrations, while at high vacancy concentrations the concerted splitting of highly aggregated nitrogen centers by the surrounding vacancies could take place in favor of resulting NV centers.

"Stealth Scripts": Ultrashort Pulse Laser Luminescent Microscale Encoding of Bulk Diamonds via Ultrafast Multi-Scale Atomistic Structural Transformations.

The ultrashort-laser photoexcitation and structural modification of buried atomistic optical impurity centers in crystalline diamonds are the key enabling processes in the fabrication of ultrasensitive robust spectroscopic probes of electrical, magnetic, stress, temperature fields, and single-photon nanophotonic devices, as well as in "stealth" luminescent nano/microscale encoding in natural diamonds for their commercial tracing. Despite recent remarkable advances in ultrashort-laser predetermined generation of primitive optical centers in diamonds even on the single-center level, the underlying multi-scale basic processes, rather similar to other semiconductors and dielectrics, are almost uncovered due to the multitude of the involved multi-scale ultrafast and spatially inhomogeneous optical, electronic, thermal, and structural elementary events. We enlighten non-linear wavelength-, polarization-, intensity-, pulsewidth-, and focusing-dependent photoexcitation and energy deposition mechanisms in diamonds, coupled to the propagation of ultrashort laser pulses and ultrafast off-focus energy transport by electron-hole plasma, transient plasma- and hot-phonon-induced stress generation and the resulting variety of diverse structural atomistic modifications in the diamond lattice. Our findings pave the way for new forthcoming groundbreaking experiments and comprehensive enlightening two-temperature and/or atomistic modeling both in diamonds and other semiconductor/dielectric materials, as well as innovative technological breakthroughs in the field of single-photon source fabrication and "stealth" luminescent nano/microencoding in bulk diamonds for their commercial tracing.

Up/Down-Scaling Photoluminescent Micromarks Written in Diamond by Ultrashort Laser Pulses: Optical Photoluminescent and Structural Raman Imaging.

Elongated photoluminescent micromarks were inscribed inside a IaAB-type natural diamond in laser filamentation regime by multiple 515 nm, 0.3 ps laser pulses tightly focused by a 0.25 NA micro-objective. The micromark length, diameter and photoluminescence contrast scaled as a function of laser pulse energy and exposure, coming to a saturation. Our Raman/photoluminescence confocal microscopy studies indicate no structural diamond damage in the micromarks, shown as the absent Raman intensity variation versus laser energy and exposition along the distance from the surface to the deep mark edge. In contrast, sTable 3NV (N3)-centers demonstrate the pronounced increase (up to 40%) in their 415 nm zero-phonon line photoluminescence yield within the micromarks, and an even higher-ten-fold-increase in NV0-center photoluminescence yield. Photogeneration of carbon Frenkel "interstitial-vacancy" (I-V) pairs and partial photolytic dissociation of the predominating 2N (A)-centers were suggested to explain the enhanced appearance of 3NV- and NV-centers, apparently via vacancy aggregation with the resulting N (C)-centers or, consequently, with 2N- and N-centers.