Catalytic Water Electrolysis by Co-Cu-W Mixed Metal Oxides: Insights from X-ray Absorption Spectroelectrochemistry.

Mixed metal oxides (MMOs) are a promising class of electrocatalysts for the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER). Despite their importance for sustainable energy schemes, our understanding of relevant reaction pathways, catalytically active sites, and synergistic effects is rather limited. Here, we applied synchrotron-based X-ray absorption spectroscopy (XAS) to explore the evolution of the amorphous Co-Cu-W MMO electrocatalyst, shown previously to be an efficient bifunctional OER and HER catalyst for water splitting. Ex situ XAS measurements provided structural environments and the oxidation state of the metals involved, revealing Co2+ (octahedral), Cu+/2+ (tetrahedral/square-planar), and W6+ (octahedral) centers. Operando XAS investigations, including X-ray absorption near-edge structure (XANES) and extended X-ray absorption fine structure (EXAFS), elucidated the dynamic structural transformations of Co, Cu, and W metal centers during the OER and HER. The experimental results indicate that Co3+ and Cu0 are the active catalytic sites involved in the OER and HER, respectively, while Cu2+ and W6+ play crucial roles as structure stabilizers, suggesting strong synergistic interactions within the Co-Cu-W MMO system. These results, combined with the Tafel slope analysis, revealed that the bottleneck intermediate during the OER is Co3+ hydroperoxide, whose formation is accompanied by changes in the Cu-O bond lengths, pointing to a possible synergistic effect between Co and Cu ions. Our study reveals important structural effects taking place during MMO-driven OER/HER electrocatalysis and provides essential experimental insights into the complex catalytic mechanism of emerging noble-metal-free MMO electrocatalysts for full water splitting.

Factors influencing quality of life and functional status in head and neck cancer patients.

OBJECTIVE: To assess the quality of life (QoL) and functional status factors of patients at various stages of treatment for head and neck cancer. STUDY DESIGN: Cross-sectional survey study. SETTING: Outpatient. METHODS: Patients over the age of 18 who received care at the Markey Head and Neck Cancer Center Clinic since 2015 were invited to complete the survey. Survey items included: demographic information, characteristics of the patient's disease and treatments, as well as an 18-item survey assessing quality of life and functional status. A follow-up for each factor asked patients to rate how important it was to them. RESULTS: Patients reported greatest difficulties with physical activity (2.18), sleep (2.20), stress (2.26), and fatigue (2.26). Patients indicated that information (3.00), medication management (2.67), and sleep (2.62) were the most important. Multimodal therapy, marital status, and education level were all found to have statistically significant associations with several QoL measures. CONCLUSION: Quality of life and functional status in patients who have undergone treatment for head and neck cancer are both affected by many factors, particularly multimodal treatment, partner support, and education level. Identifying patients who may be more affected by treatment and targeting them with additional support and resources may lead to improved QoL in patients and their caregivers. This study would suggest that efforts to support physical activity, sleep, and stress management could lead to the most significant impact.

Biogenesis of specialized lysosomes in differentiated keratinocytes relies on close apposition with the Golgi apparatus.

Intracellular organelles support cellular physiology in diverse conditions. In the skin, epidermal keratinocytes undergo differentiation with gradual changes in cellular physiology, accompanying remodeling of lysosomes and the Golgi apparatus. However, it was not known whether changes in Golgi and lysosome morphology and their redistribution were linked. Here, we show that disassembled Golgi is distributed in close physical apposition to lysosomes in differentiated keratinocytes. This atypical localization requires the Golgi tethering protein GRASP65, which is associated with both the Golgi and lysosome membranes. Depletion of GRASP65 results in the loss of Golgi-lysosome apposition and the malformation of lysosomes, defined by their aberrant morphology, size, and function. Surprisingly, a trans-Golgi enzyme and secretory Golgi cargoes are extensively localized to the lysosome lumen and secreted to the cell surface, contributing to total protein secretion of differentiated keratinocytes but not in proliferative precursors, indicating that lysosomes acquire specialization during differentiation. We further demonstrate that the secretory function of the Golgi apparatus is critical to maintain keratinocyte lysosomes. Our study uncovers a novel form of Golgi-lysosome cross-talk and its role in maintaining specialized secretory lysosomes in differentiated keratinocytes.

Enhancing precision in colorectal cancer surgery: development of an LGR5-targeting RSPO1 peptide mimetic as a contrast agent for intraoperative fluorescence molecular imaging.

Colorectal cancer (CRC) is the third most common cancer worldwide. In the United States alone, CRC was responsible for approximately 52,550 deaths in 2023, with an estimated 153,020 new cases. CRC presents with synchronous peritoneal spread in 5-10% of patients, and up to 20-50% of patients with recurrent disease will develop metachronous colorectal cancer peritoneal metastatic (CRC-PM) disease. Eradication of the tumor, tumor margins and microscopic residual disease is paramount, as microscopic residual disease is associated with local recurrences, with 5-year survival rates of less than 35%. The success of resection and reduction of residual disease depends on the accuracy with which cancer cells and normal tissue can be intra-operatively distinguished. Fluorescence Molecular Imaging (IFMI) and tumor-targeted contrast agents represent a promising approach for intraoperative detection and surgical intervention. Proper target selection, the development of scalable imaging agents and enhanced real-time tumor and tumor microenvironment imaging are critical to enabling enhanced surgical resection. LGR5 (leucine-rich repeat-containing G-protein-coupled receptor 5), a colonic crypt stem cell marker and the receptor for the R-spondins (RSPO) in the Wnt signaling pathway, is also expressed on colorectal cancer stem cells (CSC) and on CRC tumors and metastases, suggesting it could be a useful target for imaging of CRC. However, there are numerous diverging reports on the role of LGR5 in CRC therapy and outcomes. Herein, we report on the synthesis and validation of a 37 amino acid RSPO1-mimetic peptide, termed RC18, that was specifically designed to access the R-spondin binding site of LGR5 to potentially be used for interoperative imaging of CRC-PM. The receptor-binding capabilities of the RC18 indicate that direct interactions with LGR5 neither significantly increased LGR5 signaling nor blocked RSPO1 binding and signal transduction, suggesting that the RSPO1-mimetic is functionally inert, making it an attractive contrast agent for intraoperative CRC-PM imaging.

Dynamic volume-outcome association for esophagectomies: Do current volume thresholds still apply?

BACKGROUND: It is unknown if the current minimum case volume recommendation of 20 cases per year per hospital is applicable to contemporary practice. METHODS: Patients undergoing esophageal resection between 2005 and 2015 were identified in the National Cancer Database. High, medium, and low-volume hospital strata were defined by quartiles. Adjusted odds ratios and adjusted 30-day mortality between low-, medium-, and high-volume hospitals were calculated using logistic regression analyses and trended over time. RESULTS: Only 1.1% of hospitals had ≥20 annual cases. The unadjusted 30-day mortality for esophagectomy was 3.8% overall. Unadjusted and adjusted 30-day mortality trended down for all three strata between 2005 and 2015, with disproportionate decreases for low-volume and medium-volume versus high-volume hospitals. By 2015, adjusted 30-day mortality was similar in medium- and high-volume hospitals (odds ratio 1.35, 95% confidence interval 0.96-1.91). For hospitals with 20 or more annual cases the adjusted 30-day mortality was 2.7% overall. To achieve this same 30-day mortality the minimum volume threshold had lowered to 7 annual cases by 2015. CONCLUSION: Only 1.1% of hospitals meet current volume recommendations for esophagectomy. Differential improvements in postoperative mortality at low- and medium- versus high-volume hospitals have led to 7 cases in 2015 achieving the same adjusted 30-day mortality as 20 cases in the overall cohort. Lowering volume thresholds for esophagectomy in contemporary practice would potentially increase the proportion of hospitals able to meet volume standards and increase access to quality care without sacrificing quality.

Impact of early surgical complications on kidney transplant outcomes.

BACKGROUND: Kidney transplantation (KT) improves clinical outcomes of patients with end stage renal disease. Little has been reported on the impact of early post-operative surgical complications (SC) on long-term clinical outcomes following KT. We sought to determine the impact of vascular complications, urological complications, surgical site complications, and peri-graft collections within 30 days of transplantation on patient survival, graft function, and hospital readmissions. METHODS: We conducted a single-centre, observational cohort study examining adult patients (≥ 18 years) who received a kidney transplant from living and deceased donors between January 1st, 2005 and December 31st, 2015 with follow-up until December 31st, 2016 (n = 1,334). Univariable and multivariable analyses were performed with Cox proportional hazards models to analyze the outcomes of SC in the early post-operative period after KT. RESULTS: The cumulative probability of SC within 30 days of transplant was 25%, the most common SC being peri-graft collections (66.8%). Multivariable analyses showed significant relationships between Clavien Grade 1 SC and death with graft function (HR 1.78 [95% CI: 1.11, 2.86]), and between Clavien Grades 3 to 4 and hospital readmissions (HR 1.95 [95% CI: 1.37, 2.77]). CONCLUSIONS: Early SC following KT are common and have a significant influence on long-term patient outcomes.

Reducing Chronic Opioid Use: Long-term Impacts of Enhanced Recovery after Mastectomy Protocols.

OBJECTIVE: This study investigates Enhanced Recovery After Surgery (ERAS®) protocols' impact on long-term opioid and sedative use following mastectomy with or without implant-based breast reconstruction (IBBR). SUMMARY BACKGROUND DATA: ERAS® protocols for patients undergoing mastectomy with or without IBBR are associated with decreased length of stay, increased rate of same-day discharge, decreased postoperative pain, and decreased postoperative opioid requirements. However, less is known about their effect on opioid and sedative use beyond 90 days after surgery. METHODS: A retrospective review of all patients undergoing mastectomy with or without IBBR at a single institution between January 2013 and December 2019. Mastectomy ERAS® protocols were implemented in February 2017, creating two groups: pre-ERAS® and ERAS®. Baseline characteristics and prevalence of chronic opioid and sedative use were compared. Univariable and multivariable logistic regression predicted factors associated with increased odds of chronic opioid and sedative use. RESULTS: 756 patients were evaluated: 405 pre-ERAS® and 351 ERAS®. Post-ERAS®, chronic opioid use decreased in opioid-naïve (40% vs. 30%, P=0.024) and opioid-tolerant patients (58% vs. 37%, P=0.002), with no increase in chronic sedative use. There were decreased odds of chronic opioid use for all ERAS® patients (OR=0.57, 95% CI: 0.42-0.76)), and of IBBR patients, those receiving subcutaneous implants (OR=0.31, 95% CI: 0.20-0.48). There was increased chronic opioid-use odds if undergoing bilateral surgery (OR=1.54, 95% CI: 1.14-2.08), two-stage reconstruction (OR=9.78, 95% CI: 5.94-16.09), and for patients with higher PACU pain scores (OR=1.09, 95% CI: 1.03-1.14) or >150 discharge OMEs (OR=2.63, 95% CI: 1.48-4.68). CONCLUSION: ERAS® protocols for mastectomy patients with or without IBR are associated with decreases in chronic opioid use, without concomitant increases in chronic sedative use.

Evaluation of Papacarie®, Carie-Care™, BRIX3000™ and conventional hand instrumentation for caries removal in primary teeth: a randomized control study.

In the current odontological era, carious lesions are removed while tooth tissue is preserved. Most of these ideals are met by chemomechanical caries removal (CMCR) methods, which are easy and comfortable to use, differentiate and eliminate infected tissues, minimize pressure, vibration and heat, and are cost-effective. This study examines the efficacy of commercially available CMCR agents, namely Papacarie®, Carie-Care™ and BRIX3000™, and a conventional hand instrumentation method for caries removal in deciduous molars in terms of time consumption, ease of application, and pain perception. For this randomized clinical trial, 120 children aged 4 to 9 years were selected and randomly allocated to four groups of 30 patients each. Time consumption, ease of application, and pain perception were evaluated at three intervals: pre-, during- and post-caries removal, using Wong-Baker FACES (WBF) Pain Rating Scale and the Face, Legs, Activity, Cry, Consolability (FLACC) scale. The results showed that among the compared materials and conventional hand instrumentation technique, Carie-Care™ was statistically found to be the least time-consuming with a p-value of 0.019, have the least pain perception with a p-value of 0.02, and was clinically the best with respect to manipulation and handling. While all three CMCR agents aid in the removal of carious tissue, Carie-Care™ was the most effective based on time consumption, pain perception and simplicity of administration.

Therapeutic Strategies for Idiopathic Pulmonary Fibrosis - Thriving Present and Promising Tomorrow.

Idiopathic pulmonary fibrosis (IPF) is a continuous, progressive, and lethal age-related respiratory disease. It is characterized by condensed and rigid lung tissue, which leads to a decline in the normal functioning of the lungs. The pathophysiology of IPF has still not been completely elucidated, so current strategies are lagging behind with respect to improving the condition of patients with IPF and increasing their survival rate. The desire for a better understanding of the pathobiology of IPF and its early detection has led to the identification of various biomarkers associated with IPF. The use of drugs such as pirfenidone and nintedanib as a safe and effective treatment alternative have marked a new chapter in the treatment of IPF. However, nonpharmacological therapies, involving long-term oxygen therapy, transplantation of the lungs, pulmonary rehabilitation, ventilation, and palliative care for cough and dyspnea, are still considered to be beneficial as supplementary methods for IPF therapy. A major risk factor for IPF is aging, with associated hallmarks such as telomere attrition, senescence, epigenetic drift, stem cell exhaustion, loss of proteostasis, and mitochondrial dysfunction. These are promising earmarks for the development of potential therapy for the disease. In this review, we have discussed current and emerging novel therapeutic strategies for IPF, especially for targets associated with age-related mechanisms.

A review on the fate of micro and nano plastics (MNPs) and their implication in regulating nutrient cycling in constructed wetland systems.

This review discusses the micro-nano plastics (MNPs) and their interaction with physical, chemical and biological processes in a constructed wetland (CW) system that is typically used as a nature-based tertiary wastewater treatment for municipal as well as industrial applications. Individual components of the CW system such as substrate, microorganisms and plants were considered to assess how MNPs influence the CW processes. One of the main functions of a CW system is removal of nutrients like nitrogen (N) and phosphorus (P) and here we highlight the pathways through which the MNPs influence CW's efficacy of nutrient removal. The presence of morphologically (size and shape) and chemically different MNPs influence the growth rate of microorganisms important in N and P cycling, invertebrates, decomposers, and the plants which affect the overall efficiency of a CW treatment system. Certain plant species take up the MNPs, and some toxicity has been observed. This review focuses on two significant aspects: (1) the presence of MNPs in a significant concentration affects the efficiency of N and P removal, and (2) the removal of MNPs. Because MNPs reduce the enzyme activities in abundance and overproduction of ROS oxidizes the enzyme active sites, resulting in the depletion of proteins, ultimately inhibiting nitrogen and phosphorus removal within the substrate layer. The review found that the majority of the studies used sand-activated carbon (SAC), granular-activated carbon (GAC), rice straw, granular limestone, and calcium carbonate, as a substrate for CW treatment systems. Common plant species used in the CW include Phragmites, Arabidopsis thaliana, Lepidium sativum, Thalia dealbata, and Canna indica, which were also found to be dominant in the uptake of the MNPs in the CWs. The MNPs were found to affect earthworms such as Eisenia fetida, Caenorhabditis elegans, and, Enchytraeus crypticus, whereas Metaphire vulgaris were found unaffected. Though various mechanisms take place during the removal process, adsorption and uptake mechanism effectively emphasize the removal of MNPs and nitrogen and phosphorus in CW. The MNPs characteristics (type, size, and concentration) play a crucial role in the removal efficiency of nano-plastics (NPs) and micro-plastics (MPs). The enhanced removal efficiency of NPs compared to MPs can be attributed to their smaller size, resulting in a faster reaction rate. However, NPs dose variation showed fluctuating removal efficiency, whereas MPs dose increment reduces removal efficiency. MP and NPs dose variation also affected toxicity to plants and earthworms as observed from data. Understanding the fate and removal of microplastics in wetland systems will help determine the reuse potential of wastewater and restrict the release of microplastics. This study provides information on various aspects and highlights future gaps and needs for MNP fate study in CW systems.

Low Intensity Laser Therapy in Disc Derangement Disorders of Temporomandibular Joint: A Review Article / Terapia con Láser de Baja Intensidad en Trastornos de Alteración Discal de la Articulación Temporomandibular: Un Artículo de Revisión

Temporomandibular disorders embrace a number of clinical conditions that involves the masticatory musculature, temporomandibular joint (TMJ) and associated structures. The most frequent cause of TMJ disorders are disc derangement disorders which involve progressive slipping or displacement of articular disc. Various conservative treatment strategies for disc derangement disorders includes pharmacologic therapy, psychological counselling, treatment of parafunctional habits, use of occlusal splints and acupuncture which gives short term relief only. Recently, a non traumatic introduction to dentistry can be represented by low level laser therapy or soft laser therapy. It has proved to be an effective treatment modality in management of disc derangement disorders through its analgesic and anti- inflammatory effect. Therefore, the goal of this review article is to explore the use of low level laser therapy as an emerging trend in the management of disc derangement disorders of TMJ.

Los trastornos temporomandibulares abarcan una serie de condiciones clínicas que involucran la musculatura masticatoria, la articulación temporomandibular (ATM) y estructuras asociadas. La causa más frecuente de trastornos de la ATM es la alteración discal que implica el deslizamiento o desplazamiento progresivo del disco articular. Diversas estrategias de tratamiento conservador para los trastornos de alteración discal incluyen el tratamiento farmacológico, la terapia psicológica, el tratamiento de los hábitos parafuncionales, uso de férulas oclusales y acupuntura, que solamente dan un alivio a corto plazo. Recientemente, una introducción no traumática para la odontología puede ser representada por la terapia con láser de baja frecuencia o terapia de láser blando. Esta ha demostrado ser una modalidad de tratamiento eficaz en el manejo de los trastornos de alteración discal a través de su efecto analgésico y antiinflamatorio. El objetivo de este artículo es explorar el uso de la terapia con láser de baja frecuencia como una tendencia emergente en el tratamiento de los trastornos de alteración del disco de la ATM.