Electrical Pulse Stimulation Protects C2C12 Myotubes against Hydrogen Peroxide-Induced Cytotoxicity via Nrf2/Antioxidant Pathway.

Skeletal muscle contraction evokes numerous biochemical alterations that underpin exercise benefits. This present study aimed to elucidate the mechanism for electrical pulse stimulation (EPS)-induced antioxidant adaptation in C2C12 myotubes. We found that EPS significantly upregulated Nrf2 and a broad array of downstream antioxidant enzymes involved in multiple antioxidant systems. These effects were completely abolished by pretreatment with a ROS scavenger, N-acetylcysteine. MitoSOX-Red, CM-H2DCFDA, and EPR spectroscopy revealed a significantly higher ROS level in mitochondria and cytosol in EPS cells compared to non-stimulated cells. Seahorse and Oroboros revealed that EPS significantly increased the maximal mitochondrial oxygen consumption rate, along with an upregulated protein expression of mitochondrial complexes I/V, mitofusin-1, and mitochondrial fission factor. A post-stimulation time-course experiment demonstrated that upregulated NQO1 and GSTA2 last at least 24 h following the cessation of EPS, whereas elevated ROS declines immediately. These findings suggest an antioxidant preconditioning effect in the EPS cells. A cell viability study suggested that the EPS cells displayed 11- and 36-fold higher survival rates compared to the control cells in response to 2 and 4 mM H2O2 treatment, respectively. In summary, we found that EPS upregulated a large group of antioxidant enzymes in C2C12 myotubes via a contraction-mitochondrial-ROS-Nrf2 pathway. This antioxidant adaptation protects cells against oxidative stress-associated cytotoxicity.

Advancements in Pancreatic Cancer Detection: Integrating Biomarkers, Imaging Technologies, and Machine Learning for Early Diagnosis.

Artificial intelligence (AI) has come to play a pivotal role in revolutionizing medical practices, particularly in the field of pancreatic cancer detection and management. As a leading cause of cancer-related deaths, pancreatic cancer warrants innovative approaches due to its typically advanced stage at diagnosis and dismal survival rates. Present detection methods, constrained by limitations in accuracy and efficiency, underscore the necessity for novel solutions. AI-driven methodologies present promising avenues for enhancing early detection and prognosis forecasting. Through the analysis of imaging data, biomarker profiles, and clinical information, AI algorithms excel in discerning subtle abnormalities indicative of pancreatic cancer with remarkable precision. Moreover, machine learning (ML) algorithms facilitate the amalgamation of diverse data sources to optimize patient care. However, despite its huge potential, the implementation of AI in pancreatic cancer detection faces various challenges. Issues such as the scarcity of comprehensive datasets, biases in algorithm development, and concerns regarding data privacy and security necessitate thorough scrutiny. While AI offers immense promise in transforming pancreatic cancer detection and management, ongoing research and collaborative efforts are indispensable in overcoming technical hurdles and ethical dilemmas. This review delves into the evolution of AI, its application in pancreatic cancer detection, and the challenges and ethical considerations inherent in its integration.

School Attendance Among Pediatric Oncology Patients During the COVID-19 Pandemic in Ontario, Canada.

Supporting schooling for current and past pediatric oncology patients is vital to their quality of life and psychosocial recovery. However, no study has examined the perspectives toward in-person schooling among pediatric oncology families during the COVID-19 pandemic. In this online survey study, we determined the rate of and attitudes toward in-person school attendance among current and past pediatric oncology patients living in Ontario, Canada during the 2020-2021 school year. Of our 31-family cohort, 23 children (74%) did attend and 8 (26%) did not attend any in-person school during this time. Fewer children within 2 years of treatment completion attended in-person school (5/8; 62%) than those more than 2 years from treatment completion (13/15; 87%). Notably, 22 of 29 parents (76%) felt that speaking to their care team had the greatest impact compared to other potential information sources when deciding about school participation, yet 13 (45%) were unaware of their physician's specific recommendation regarding whether their child should attend. This study highlights the range in parental comfort regarding permitting in-person schooling during the COVID-19 pandemic. Pediatric oncologists should continue to address parental concerns around in-person school during times of high transmission of COVID-19 and potentially other communicable diseases in the future.

A qualitative study of what motivates and enables climate-engaged physicians in Canada to engage in health-care sustainability, advocacy, and action.

Increasing numbers of health-care professionals are aware of the need to deliver low-carbon sustainable health systems. We aimed to explore how physicians can be motivated and supported to pursue this ambition by conducting an exploratory qualitative descriptive study that involved individual in-depth interviews with climate-engaged Canadian physicians participating in health-care sustainability advocacy and action. Interview transcripts were analysed to identify themes related to the actions that physicians can take to promote sustainable health care, and the motivators and enablers of physician engagement in sustainable health care. Participants (n=19) engaged in a spectrum of health-care sustainability initiatives ranging from reducing health-care waste to lobbying and political action. They were motivated to advance health-care sustainability by their concern about the health implications of climate change, frustration with health-care waste, and recognition of their locus of influence as physicians. Participants articulated that policy and system, organisational and team, and knowledge generation and translation supports are required to strengthen their capacity to advance health-care sustainability. These findings can provide inspiration for engagement opportunities in health-care sustainability, guide service delivery and educational innovations to promote health-care professionals' interest in becoming sustainability champions, and extend the capacity of health-care professionals to reduce the climate impact of health care.

Metal ferrite incorporated polysulfone thin-film nanocomposite membranes for wastewater treatment.

Effluents from food, fermentation, and sugar industries contain a large quantity of glucose which has to be removed to limit the chemical oxygen demand (COD) of the water discharged. This work proposes novel thin-film nanocomposite (TFN) membranes incorporated with MgFe2O4 and ZnFe2O4 nanoparticles to address this concern. The nanoparticles synthesized by the sol-gel method was extensively characterized and then incorporated into the active polyamide layer of the thin-film composite polysulfone membranes. The change in membrane morphology, wettability, chemical structure, and mechanical strength with the incorporation of nanoparticles was studied in detail. Membranes with 0.005 wt.% MgFe2O4 nanoparticle exhibited highest glucose rejection (96.52 ± 2.35%) at 10 bar, 25 °C, and sufficiently high pure water flux (50.54 ± 1.92 L/m2h). This membrane also displayed 69.1 ± 5.12% salt rejection when challenged with 2000 ppm synthetic NaCl solution.

Biological characterization of surface-treated dental implant materials in contact with mammalian host and bacterial cells: titanium versus zirconia.

Commercially pure titanium (cpTi) remains the material of choice for dental implants due to its surface properties which promote osseointegration. Recently, zirconia (ZrO2) has been used as an alternative material due to its immunity to corrosion, mechanical strength, and biocompatibility. Previous in vitro studies evaluating oral bacterial attachment and mammalian host cell response to cpTi and ZrO2 have yielded mixed results. Thus, the aim of the present study was to systematically evaluate the growth of early-colonizing oral bacteria and mammalian host cells on cpTi and ZrO2 after three clinically-relevant surface treatments: polishing, acid-etching, or sandblasting. Polishing produced smooth surfaces (Sa: 0.08-0.22 µm) while acid-etching (Sa: 0.75-1.20 µm) and sandblasting (Sa: 0.87-1.00 µm) yielded rough variants. All surfaces were relatively hydrophilic (θ c ≤ 31°). Overall, the adherent bacterial count did not significantly differ between cpTi and ZrO2 after 1 or 3 days for all Streptococcus strains (p > 0.05). Bacterial count was only greater on rough versus smooth variants for S. sanguinis and S. salivarius. Acid-etched cpTi induced the highest proliferation of macrophages and fibroblasts but the lowest for pre-osteoblasts after 1 and 3 days. All surfaces exhibited comparable fibroblast and pre-osteoblast proliferation by 7 days. Pre-osteoblast differentiation continually increased between 7 and 14 days and was higher on rougher surfaces. No differences in mammalian cellular attachment on cpTi and ZrO2 were observed. Within the study's limitations, early-colonizing oral bacterial adhesion and mammalian cell growth is similar on both smooth and rough cpTi and ZrO2.

Can Oral Bacteria and Mechanical Fatigue Degrade Zirconia Dental Implants in Vitro?

Zirconia (ZrO2) is an emerging alternative to titanium for dental implant systems due to its material properties including high mechanical strength and chemical stability. However, oral environmental factors such as bacterial adhesion and mechanical fatigue may trigger low-temperature degradation of ZrO2, leading to reduced mechanical strength and potential implant fracture. Although failure modes of ZrO2 in orthopedic applications have been studied, they have yet to be thoroughly investigated in the context of dental implant systems. Thus, the goal of the present study was to assess the surface of ZrO2 dental implants for signs of degradation after exposure to oral bacteria and oral bacteria in combination with mechanical fatigue. ZrO2 dental implants were subjected to 30-day immersion in (i) early or (ii) late colonizing oral bacteria or (iii) were mechanically loaded for 2 × 106 cycles with oral bacteria in circulation. Optical microscopy, Raman microscopy, and X-ray photoelectron spectroscopy (XPS) were used to evaluate the surface morphology, phase composition, and chemical composition, respectively. Post-immersion, all implants exhibited minimal changes in surface features, and all loaded implants survived cyclic fatigue tests. All implants had <1% monoclinic phase at the collar, junction, and screw regions, excluding the screw threads, for which monoclinic phase was significantly higher but <10%. XPS revealed an increase in carbon- and nitrogen-based organic debris on the implants exposed to early colonizers as compared to those immersed in late colonizers or synergistically with mechanical loading. Within the limitations of the present study, ZrO2 is a suitable alternative material for dental implant systems based on its ability to resist both physical and chemical degradation imposed by oral bacteria and applied cyclic loads.

Middle cerebral artery involvement in systemic lupus erythematosus presenting as a stroke--an unusual initial presentation of the disease.

Systemic lupus erythematosus (SLE) disproportionately affects the African American population and usually presents with a constellation of symptoms. Along with hematologic, musculoskeletal, serous and skin involvement, the most common causes of morbidity are attributed to altered blood rheology causing accelerated atherosclerotic vascular disease (ASVD). ASVD occurs in predominantly premenopausal women at an age where ASVD is rare or uncommon. Classical central nervous system manifestations are very rare from the outset of the disease. Here we present a 44-year old African American woman with newly diagnosed SLE and no significant atherosclerotic risk factors, who presented initially with symptoms of subacute stroke.

Amyloid-beta peptide inhibits activation of the nitric oxide/cGMP/cAMP-responsive element-binding protein pathway during hippocampal synaptic plasticity.

Amyloid-beta (Abeta), a peptide thought to play a crucial role in Alzheimer's disease (AD), has many targets that, in turn, activate different second-messenger cascades. Interestingly, Abeta has been found to markedly impair hippocampal long-term potentiation (LTP). To identify a new pathway that might be responsible for such impairment, we analyzed the role of the nitric oxide (NO)/soluble guanylyl cyclase (sGC)/cGMP/cGMP-dependent protein kinase (cGK)/cAMP-responsive element-binding protein (CREB) cascade because of its involvement in LTP. The use of the NO donor 2-(N,N-dethylamino)-diazenolate-2-oxide diethylammonium salt (DEA/NO), the sGC stimulator 3-(4-amino-5-cyclopropylpyrimidine-2-yl)-1-(2-fluorobenzyl)-1H-pyrazolo[3,4-b]pyridine, or the cGMP-analogs 8-bromo-cGMP and 8-(4-chlorophenylthio)-cGMP reversed the Abeta-induced impairment of CA1-LTP through cGK activation. Furthermore, these compounds reestablished the enhancement of CREB phosphorylation occurring during LTP in slices exposed to Abeta. We also found that Abeta blocks the increase in cGMP immunoreactivity occurring immediately after LTP and that DEA/NO counteracts the effect of Abeta. These results strongly suggest that, when modulating hippocampal synaptic plasticity, Abeta downregulates the NO/cGMP/cGK/CREB pathway; thus, enhancement of the NO/cGMP signaling may provide a novel approach to the treatment of AD and other neurodegenerative diseases with elevated production of Abeta.

Cell cultures from animal models of Alzheimer's disease as a tool for faster screening and testing of drug efficacy.

Approximately 2 million people in the United States suffer from Alzheimer's disease (AD), which is the most common cause of chronic dementia among the aging population. During the last 7 yr, excellent opportunities to screen drugs against AD have been provided by animal models of the disease. Because even in the fastest model, AD pathology does not start before the end of the second month, it has been necessary to wait at least until that age to inject drugs into the animal to assess whether they prevent, reduce, or revert synaptic impairment, plaque formation, and increase of beta-amyloid (Abeta) levels, the main features of the disease. A solution to the problems mentioned above is achieved by the present fast, efficient, and reproducible cultured cell system from animal models of AD or Abeta-associated diseases, for the screening and testing of compounds for the treatment and therapy of AD or Abeta-associated diseases.

Strain-Induced "Band Flips" in Cyclodecaamylose and Higher Homologues.

The cavity of the larger molecule has less space for guests! Unlike the structure of the smaller annular cyclodextrins, that of the higher homologues of cycloamyloses (CAs) with more than ten glucose units contains a 90° kink between adjacent glucose residues within one half of the molecule and a 180° band flip between adjacent units in different halves (see depicted section of the CA14 structure) to yield butterfly-shaped structures with narrow, groovelike cavities.