Search Results (245)

The aims of the current study included gathering cultural knowledge and stories regarding parenting young children within a Tribal community and learning community members’ perspectives on key components of a promising parenting prevention program. Qualitative data were drawn from a focus group including seven participants and semi-structured phone interviews with 21 additional participants, all of whom were parenting children in the community. Hybrid coding and applied thematic analysis revealed five themes: (1) Desire to Learn and Gain Parenting Skills; (2) Relationships and the Caregiver Role; (3) Culture and Caregiving, which included subthemes of Diversity Among Tribal Bands, Intergenerational Knowledge Sharing, and Reconnection and Revitalization; (4) Historical Trauma and Behavioral Health; and (5) Curriculum Terminology Considerations. The information gathered collectively informed the development of the culturally grounded stim’ aspuʔús (What’s in Your Heart?) parenting program. This addresses the great need for culturally grounded interventions to support trauma healing within Indigenous families. The development process and implications for program development by and for Indigenous communities is discussed. Full article

In the evolving field of quantum computing, optimizing Quantum Error Correction (QEC) parameters is crucial due to the varying types and amounts of physical noise across quantum computers. Traditional simulators use a forward paradigm to derive logical error rates from inputs like code distance and rounds, but this can lead to resource wastage. Adjusting QEC parameters manually with tools like STIM is often inefficient, especially given the daily fluctuations in quantum error rates. To address this, we introduce MITS, a reverse engineering tool for STIM that automatically determines optimal QEC settings based on a given quantum computer’s noise model and a target logical error rate. This approach minimizes qubit and gate usage by precisely matching the necessary logical error rate with the constraints of qubit numbers and gate fidelity. Our investigations into various heuristics and machine learning models for MITS show that XGBoost and Random Forest regressions, with Pearson correlation coefficients of $0.98$ and $0.96$, respectively, are highly effective in this context. Full article

This study compared the DuoStim protocol with two conventional follicular phase stimulations for vitrified oocyte accumulation in poor-prognosis patients undergoing PGT-A. A retrospective analysis of 112 IVF cycles was conducted, with 66 cycles among patients undergoing DuoStim (DS-Group) and 46 among patients undergoing conventional follicular phase stimulations (DF-Group). The primary outcome was the time to live birth, while secondary outcomes included clinical pregnancy rate, miscarriage rate, live birth rate, and cumulative live birth rate. The final analysis included 66 patients in the DS-Group and 40 in the DF-Group, as 6 women (13%) in the DF-Group discontinued treatment after the first stimulation. Oocyte yield was similar between groups (8.4 ± 3.9 in DS-Group vs. 8.2 ± 4.0 in DF-Group, p = 0.80), as was the number of euploid blastocysts (0.9 ± 1.2 vs. 1.1 ± 1.1, p = 0.37). The cumulative live birth rate was 22.7% in the DS-Group and 25% in the DF-Group (multivariate odds ratio adjusted for maternal age and male factor: 1.05, p = 0.93). The time to live birth was significantly shorter in the DS-Group (81.5 ± 15.5 days) compared to the DF-Group (153.7 ± 78.2 days, p < 0.001). DuoStim showed similar efficacy but a shorter time to live birth. Full article

Background/Objectives: Whole-genome sequencing (WGS) data provide valuable information about the genetic architecture of local livestock but have not yet been applied to Russian native goats, in particular, the Orenburg and Karachay breeds. A preliminary search for selection signatures based on single nucleotide polymorphism (SNP) genotype data in these breeds was not informative. Therefore, in this study, we aimed to address runs of homozygosity (ROHs) patterns and find the respective signatures of selection overlapping candidate genes in Orenburg and Karachay goats using the WGS approach. Methods: Paired-end libraries (150 bp reads) were constructed for each animal. Next-generation sequencing was performed using a NovaSeq 6000 sequencer (Illumina, Inc., San Diego, CA, USA), with ~20X genome coverage. ROHs were identified in sliding windows, and ROH segments shared by at least 50% of the samples were considered as ROH islands. Results: ROH islands were identified on chromosomes CHI3, CHI5, CHI7, CHI12, CHI13, and CHI15 in Karachay goats; and CHI3, CHI11, CHI12, CHI15, and CHI16 in Orenburg goats. Shared ROH islands were found on CHI12 (containing the PARP4 and MPHOSPH8 candidate genes) and on CHI15 (harboring STIM1 and RRM1). The Karachay breed had greater ROH length and higher ROH number compared to the Orenburg breed (134.13 Mb and 695 vs. 78.43 Mb and 438, respectively). The genomic inbreeding coefficient (F_ROH) varied from 0.032 in the Orenburg breed to 0.054 in the Karachay breed. Candidate genes associated with reproduction, milk production, immunity-related traits, embryogenesis, growth, and development were identified in ROH islands in the studied breeds. Conclusions: Here, we present the first attempt of elucidating the ROH landscape and signatures of selection in Russian local goat breeds using WGS analysis. Our findings will pave the way for further insights into the genetic mechanisms underlying adaption and economically important traits in native goats. Full article

Multiple Sclerosis (MS) is a chronic autoimmune disorder characterized by demyelination and neuronal damage in the central nervous system. Dysregulation of calcium homeostasis, particularly through the Store-Operated Calcium Entry-Associated Regulatory Factor (SARAF), has been implicated in MS pathogenesis. This study investigated SARAF, STIM1, and Orai1 expression patterns and their relationship to calcium homeostasis in 45 Bahraini MS patients and 45 matched healthy controls using ELISA and real-time PCR analyses. MS patients showed significantly elevated serum SARAF levels in both early (192.26 ± 47.00 pg/mL) and late MS stages (341.47 ± 96.19 pg/mL) compared to controls (129.82 ± 30.82 pg/mL; p < 0.001. SARAF expressions were markedly increased in MS patients (3.829 ± 0.04422 vs. 1 ± 0; p < 0.0001), while STIM1 (0.4324 ± 0.01471) and ORAI1 (0.2963 ± 0.02156) expressions were significantly reduced compared to the controls (p < 0.0001). Intracellular calcium levels were notably elevated in both early and late MS stages. These findings suggest that the progressive elevation of SARAF, coupled with altered STIM1 and ORAI1 expression, may serve as potential biomarkers for MS progression and represent promising therapeutic targets. Full article

Hepatocellular carcinoma (HCC), a highly aggressive liver malignancy, is often associated with disrupted calcium homeostasis. Store-operated calcium entry (SOCE), involving components such as STIM1, Orai1, and SARAF, plays a critical role in calcium signaling and cancer progression. While STIM1 and Orai1 have been extensively studied, SARAF’s role as a negative regulator of SOCE in HCC remains poorly understood. This preliminary study investigated SARAF’s effects on calcium homeostasis, proliferation, and migration in HepG2 liver cancer cells, providing initial evidence of its tumor-suppressive role. SARAF expression was modulated using siRNA knockdown and overexpression plasmids, with validation by qRT-PCR. Functional assays demonstrated that SARAF silencing increased proliferation by 50% and migration by 40% (p < 0.05), while SARAF overexpression reduced proliferation by 50% and migration by 45% (p < 0.01), highlighting its tumor-suppressive role. Intracellular calcium levels, elevated in HepG2 cells, were partially restored by SARAF overexpression, though SARAF silencing did not further disrupt calcium regulation. These findings suggest that SARAF negatively regulates proliferation and migration in HCC, potentially through its role in maintaining calcium homeostasis. SARAF represents a promising therapeutic target in HCC. Future studies should explore the downstream molecular mechanisms governing SARAF’s effects, investigate its role in other cancers, and assess its clinical potential for liver cancer therapy. Full article

The amygdala, especially its central nucleus (CeA), is one of the key brain structures regulating fear, anxiety and stress responses and is also involved in gut microbiota signal processing. Amygdala hyperactivity, as well as microbiota alterations, plays an important role in the pathophysiology of anxiety disorders, depression or post-traumatic stress disorder (PTSD). The present study determines whether 3 weeks of galactooligosaccharide (GOS) supplementation alleviates behavioural, haematological, immunological and gut microbiota disturbances induced by long-term electrical stimulation of the CeA in rats (Stim). The unsupplemented Stim group showed locomotor hyperactivity and higher anxiety (measured with an actometer and the elevated plus maze, respectively), as well as a decrease in white blood cells (WBCs), lymphocytes (LYMs), red blood cells (RBCs) and platelets (PLTs); an elevation of TNFα; a reduction in IL-10 concentration in plasma; and microbiota alterations as compared to the control (Sham) group. GOS supplementation alleviated all these Stim-induced adverse effects or even normalised them to the sham group level. The effect of GOS was comparable to citalopram and even more effective in WBC and PLT normalisation and IL-10 induction. The obtained results indicate the high therapeutic potential of GOS in anxiety and stress-related disorders. GOS supplementation may support conventional therapy or the prevention of PTSD, depression and anxiety disorders. Full article

We investigated the effects of belt electrode-skeletal muscle electrical stimulation (B-SES) on muscle atrophy in collagen-induced arthritis (CIA) rats. Twenty-eight 8-week-old male Dark Agouti rats were immunized with type II collagen and Freund’s incomplete adjuvant (day 0). From days 14 to 28, 18 rats received B-SES (50 Hz) four times only on the right hindlimb (STIM), while the contralateral left hindlimb remained unstimulated. Both hindlimbs of 10 untreated CIA rats were defined as controls (CONT). Paw volume was measured every other day. On day 28, the muscle weight, histology, and gene expression of the soleus and extensor digitorum longus (EDL) were analyzed. B-SES did not worsen paw volume throughout the experimental period. Compared with CONT, the muscle weight and fiber cross-sectional area of the soleus were higher in STIM. The expression of muscle degradation markers (atrogin-1 and MuRF-1) in the soleus and EDL was lower in the STIM group than that in the CONT group. In contrast, B-SES did not significantly affect the expression of muscle synthesis (Eif4e and p70S6K) and mitochondrial (PGC-1α) markers. B-SES prevents muscle atrophy in CIA rats by reducing muscle degradation without exacerbating arthritis, demonstrating its promising potential as an intervention for RA-induced muscle atrophy. Full article

In this study, we present a proof-of-concept neuroelectronic interface (NEI) for extracellular stimulation and recording of neurophysiological activity in spiral ganglion neurons (SGNs) cultured in vitro on three-dimensional, micro-patterned substrates with customized microtopographies, integrated within a 196-channel microelectrode array (MEA). This approach enables mechanotaxis-driven neuronal contact guidance, promoting SGN growth and development, which is highly sensitive to artificial in vitro environments. The microtopography geometry was optimized based on our previous studies to enhance SGN alignment and neuron-electrode interactions. The NEI was validated using SGNs dissociated from rat pups in the prehearing period and cultured for seven days in vitro (DIV). We observed viable and proliferative cellular cultures with robust neurophysiological responses in the form of local field potentials (LFPs) resembling action potentials (APs), elicited both spontaneously and through electrical stimulation. These findings provide deeper insights into SGN behavior and neuron-microenvironment interactions, laying the groundwork for further advancements in neuroelectronic systems. Full article

Cardiac fibrosis is a scarring event that occurs in the myocardium in response to multiple cardiovascular disorders, such as acute myocardial infarction (AMI), ischemic cardiomyopathy, dilated cardiomyopathy, hypertensive heart disease, inflammatory heart disease, diabetic cardiomyopathy, and aortic stenosis. Fibrotic remodeling is mainly sustained by the differentiation of fibroblasts into myofibroblasts, which synthesize and secrete most of the extracellular matrix (ECM) proteins. An increase in the intracellular Ca²⁺ concentration ([Ca²⁺]_i) in cardiac fibroblasts is emerging as a critical mediator of the fibrogenic signaling cascade. Herein, we review the mechanisms that may shape intracellular Ca²⁺ signals involved in fibroblast transdifferentiation into myofibroblasts. We focus our attention on the functional interplay between inositol-1,4,5-trisphosphate (InsP₃) receptors (InsP₃Rs) and store-operated Ca²⁺ entry (SOCE). In accordance with this, InsP₃Rs and SOCE drive the Ca²⁺ response elicited by G_q-protein coupled receptors (G_qPCRs) that promote fibrotic remodeling. Then, we describe the additional mechanisms that sustain extracellular Ca²⁺ entry, including receptor-operated Ca²⁺ entry (ROCE), P2X receptors, Transient Receptor Potential (TRP) channels, and Piezo1 channels. In parallel, we discuss the pharmacological manipulation of the Ca²⁺ handling machinery as a promising approach to mitigate or reverse fibrotic remodeling in cardiac disorders. Full article

This study aim to compare the extraction yield, antioxidant potential, and chemical composition of Chaetoceros costatus extracted with acetone, ethanol, and hexane. The freeze-dried diatom biomass was extracted by ultrasonication for 1 h at 40 °C. The antioxidant capacity was determined using 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging and oxygen radical absorbance capacity (ORAC), while the chemical profiles of the extracts were analyzed using high-performance liquid chromatography with high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The ORAC assay showed a 27% higher activity of the acetone extract, while the DPPH assay showed almost 3-fold higher DPPH inhibition. Pigments, fatty acids, sterols, and their derivatives were identified in all extracts. The chemical composition of ethanolic and acetonic extracts did not differ significantly, and hexane yielded the fewest compounds. The results of this study will contribute to extraction challenges that limit biotechnological application and exploitation of diatoms. Full article

Microbial eukaryotes have essential roles in aquatic ecosystems, yet their diversity and ecological functions in extreme environments remain understudied compared to prokaryotes. This study aims to thoroughly characterize the composition and diversity of microbial eukaryotic communities in 14 geothermal waters across Croatia. Physicochemical analysis revealed significant variations in temperature (36–55 °C), pH (6.5–8.3), and nutrient concentrations, with all sites displaying anoxic conditions except for one. Sequencing of the V9 18S rRNA gene identified 134 taxa, predominantly from the Alveolata, Stramenopiles, and Opisthokonta supergroups. The highest diversity and richness were observed in aquifer groups with moderate temperatures and nutrient levels, while extreme sites exhibited reduced diversity. Among the key environmental factors shaping these communities, temperature, pH, and nitrate concentrations were most significant. Photoautotrophic and mixotrophic taxa, such as Ochrophyta, Dinoflagellata, and Chlorophyta, were prominent, reflecting their roles in primary production and nutrient cycling. Decomposers, including Basidiomycota and Ascomycota, were linked to organic matter degradation. Microeukaryotes showed adaptations to extreme conditions, such as thermotolerance and evolutionary shifts from phototrophy to heterotrophy, highlighting their ecological versatility. These findings underscore the potential of microbial eukaryotes in biotechnological applications, such as bioremediation and biofuel production. Genera like Tribonema and Navicula demonstrated promising capabilities in nutrient removal and CO₂ fixation. However, further research is necessary to investigate and confirm their suitability for these purposes. To summarize, our research provides new insights into understudied microbial eukaryotes in Croatian hot springs that represent a valuable model for exploring microbial diversity, ecological interactions, and industrial applications in extreme environments. Full article

This research evaluates the mineral ions and their concentrations in formation water from five well samples of the Bibi Hakimeh oil field (Iran). The analysis reveals the presence of calcium (Ca²⁺), sodium (Na⁺), and magnesium (Mg²⁺) cations, as well as sulfate (SO₄²⁻), bicarbonate (HCO₃⁻), and chloride (Cl⁻) anions, which are soluble in water within the Bibi Hakimeh oil formation. Furthermore, mineral deposits of CaSO₄, CaSO₄.2H₂O, CaCO₃, and MgCO₃ are investigated and predicted using StimCADE 2 software. The findings highlight the significant chemical precipitation of calcium sulfate and calcium carbonate mineral deposits under the operating conditions of the Bibi Hakimeh oil well. The geochemical composition of the formation waters is discussed to understand the equilibrium conditions and possible influence of the physical parameters. Additionally, this study examines the interaction between rock and water of the Bibi Hakimeh formation, revealing a notable correlation between the concentration of calcium and magnesium ions and the water–rock reaction in this field. Full article

Gastroesophageal reflux disease (GERD) affects millions globally, with traditional treatments like proton pump inhibitors (PPIs) and surgical fundoplication presenting challenges such as long-term medication dependency and disturbing long term side effects following surgery. This review explores emerging, alternative therapies that offer less invasive, personalized alternatives for GERD management. Endoscopic approaches, including Stretta therapy, transoral incisionless fundoplication (TIF), and endoscopic full-thickness plication (EFTP), demonstrate promising but also controversial outcomes in symptom relief and reduced acid exposure. Laparoscopic electrical stimulation therapy (EndoStim^®) and the LINX^® magnetic sphincter augmentation system address LES dysfunction, while endoscopic anti-reflux mucosectomy and/or ablation techniques aim to construct a sufficient acid barrier. The RefluxStop™ device offers structural solutions to GERD pathophysiology with intriguing results in initial studies. Despite promising results, further research is required to establish long-term efficacy, safety, and optimal patient selection criteria for these novel interventions. This review underscores the importance of integrating emerging therapies into a tailored, multidisciplinary approach to GERD treatment. Full article

Injured or atrophied adult skeletal muscles are regenerated through terminal differentiation of satellite cells to form multinucleated muscle fibers. Transplantation of satellite cells or cultured myoblasts has been used to improve skeletal muscle regeneration. Some of the limitations observed result from the limited number of available satellite cells that can be harvested and the efficiency of fusion of cultured myoblasts with mature muscle fibers (i.e., terminal differentiation) upon transplantation. However, the possible use of immature myotubes in the middle of the terminal differentiation process instead of satellite cells or cultured myoblasts has not been thoroughly investigated. Herein, myoblasts (Mb) or immature myotubes on differentiation day 2 (D2 immature myotubes) or 3 (D3 immature myotubes) were transferred to plates containing D2 or D3 immature myotubes as host cells. The transferred Mb/immature myotubes on the plates were further co-differentiated with host immature myotubes into mature myotubes in six conditions: Mb-to-D2, D2-to-D2, D3-to-D2, Mb-to-D3, D2-to-D3, and D3-to-D3. Among these six co-differentiation conditions, the D2-to-D3 co-differentiation condition exhibited the most characteristic myotube appearance and the greatest availability of Ca²⁺ for skeletal muscle contraction. Compared with non-co-differentiated control myotubes, D2-to-D3 co-differentiated myotubes presented increased MyoD and myosin heavy chain II (MyHC II) expression and increased myotube width, accompanied by parallel and swirling alignment. These increases correlated with functional increases in both electrically induced intracellular Ca²⁺ release and extracellular Ca²⁺ entry due to the increased expression of ryanodine receptor 1 (RyR1), sarcoplasmic/endoplasmic reticulum Ca²⁺-ATPase 1a (SERCA1a), and stromal interaction molecule 1 (STIM1). These increases were not detected in any of the other co-differentiation conditions. These results suggest that in vitro-cultured D2-to-D3 co-differentiated mature myotubes could be a good alternative source of satellite cells or cultured myoblasts for skeletal muscle regeneration. Full article