An assessment of the clinical relevance of coracoid graft osteolysis following the Latarjet procedure: a clinical and radiological review.

Background: The Latarjet procedure was developed for the treatment of anterior shoulder instability in young, high-demand patients with attritional glenoid bone loss, whose risk of redislocation following primary dislocation may exceed 90%. Coracoid graft osteolysis and prominent screws are commonly observed in late computed tomography (CT) scans of patients who re-present following the procedure, but the clinical relevance of osteolysis in the overall Latarjet cohort is undetermined. We aimed to evaluate clinical and radiological outcomes in patients who underwent the Latarjet procedure, and to determine if severe coracoid graft osteolysis compromised clinical outcomes. Methods: This was a retrospective analysis of patients who underwent the open Latarjet procedure. Patients were invited via an e-questionnaire that contained a Western Ontario Shoulder Instability Index (WOSI), and queried about redislocation and reoperation since index surgery. Preoperative glenoid bone loss was calculated on CT using the best-fit circle method. Osteolysis was graded (0, screw head buried in graft; 1, screw head exposed; 2, threads exposed; 3, complete resorption/severe osteolysis) at the level of the proximal and distal screws respectively, on axial CT scans performed ≥ 12 months postoperatively. Results: Between 2011 and 2022, a single surgeon performed 442 Latarjet procedures. One hundred fifty eight patients responded to the questionnaire at median (interquartile range [IQR]) 44 (27-70) months postoperatively, among whom the median (IQR) WOSI score was 352 (142-666) points (0 = best, 2100 = worst). Recurrent anterior instability occurred in 3/158 (2%) patients. One patient required reoperation for this indication. Among patients who had CT scans ≥ 12 months postoperatively (median [IQR] 40 [29-69] months), 1 patient developed severe osteolysis around both screws (WOSI = 90), 17/62 (27%) patients developed severe osteolysis around 1 screw, all of which were proximal (median [IQR] WOSI = 235 [135-644]), and 44/62 (71%) patients did not develop severe osteolysis around either screw (median [IQR] WOSI = 487 [177-815]). There were no statistically significant differences in WOSI scores between groups based on the presence of severe osteolysis. Conclusion: The Latarjet is reliable procedure that has a low rate of redislocation and reoperation. Severe coracoid graft osteolysis occurs with time, and always affects the proximal graft first. The presence of severe osteolysis did not compromise clinical outcomes.

La-Fe-O Perovskite Based Gas Sensors: Recent Advances and Future Challenges.

Interest in the importance of gas sensing devices has increased significantly due to their critical function in monitoring the environment and controlling pollution, resulting in an increased market demand. The present review explores perovskite La-Fe-O based gas sensors with a special focus on LaFeO3 and evaluates their sensitivity to a diverse range of practical target gases that need to be monitored. An analysis has been conducted to assess different routes not only of synthesizing LaFeO3 material but also of characterization with the targeted use for their gas sensing abilities. Additionally, a comprehensive analysis has been performed to explore the effect of introducing other elements through doping. In view of the LaFeO3 sensing performance, more common gases like acetone, ethanol, methanol, formaldehyde, NO x , and CO2 have been targeted. In addition, a discussion on uncommon gases such as CO, SO2, TEA, C2H5, C6H6, and others is also made to give a complete picture of LaFeO3-based gas sensors. The summary and conclusion section of the study addresses the primary obstacles in the synthesis process, the variables that restrict the sensing capabilities of LaFeO3, and its commercial fulfillment.

AMRomics: a scalable workflow to analyze large microbial genome collections.

Whole genome analysis for microbial genomics is critical to studying and monitoring antimicrobial resistance strains. The exponential growth of microbial sequencing data necessitates a fast and scalable computational pipeline to generate the desired outputs in a timely and cost-effective manner. Recent methods have been implemented to integrate individual genomes into large collections of specific bacterial populations and are widely employed for systematic genomic surveillance. However, they do not scale well when the population expands and turnaround time remains the main issue for this type of analysis. Here, we introduce AMRomics, an optimized microbial genomics pipeline that can work efficiently with big datasets. We use different bacterial data collections to compare AMRomics against competitive tools and show that our pipeline can generate similar results of interest but with better performance. The software is open source and is publicly available at https://github.com/amromics/amromics under an MIT license.

Dietary Intake, Menopausal Symptoms, and Body Composition Associated with Possible Sarcopenia Among Vietnamese Middle-Aged Women: A Cross-Sectional Study.

Background: This study aims to investigate the prevalence of possible sarcopenia and its associated factors among middle-aged Vietnamese women. Methods: A cross-sectional study was conducted on 205 women aged 40-55 years who were admitted to the Can Tho Obstetrics and Gynecology Hospital between February and December 2023. The presence of possible sarcopenia was determined according to the AWGS 2019 criteria. Associated factors were dietary intake (total energy, protein, lipid, and carbohydrate intake), the severity of menopausal symptoms by using the Kupperman index, and body composition by using the bioelectrical impedance analysis device, Inbody S10. Logistic regressions were built to analyze the association between possible sarcopenia and its associated factors. Results: The prevalence of possible sarcopenia was 29.8%, with a mean age of 47.2. Possible sarcopenia was detected in 23% of the participants based on the criterion of low handgrip strength, whereas 83.6% of the participants when considered low performance in the chair stand test. Adjusted logistic regression analysis showed that living in a rural area (adjusted odds ratio [AOR]: 2.16, 95% confidence interval [95% CI]: 1.22-4.72), energy intake <25 kcal/body weight, (AOR: 1.94, 95% CI: 1.75-5.06), protein intake <0.91 g/body weight (AOR: 2.42, 95% CI: 1.51-5.76), skipping breakfast (AOR: 2.03, 95% CI: 0.91-4.54), mild menopausal symptoms (AOR: 2.68, 95% CI: 1.61-5.36), and obesity (AOR: 1.59, 95%CI: 1.29-3.67) were significantly associated with higher risk of possible sarcopenia. Conversely, higher muscle mass and higher upper limb mass were associated with a decreased risk of possible sarcopenia (total muscle mass AOR: 0.20, 95% CI: 0.07-0.59). Conclusions: These findings would provide a basis for enhancing management and prevention strategies to reduce the risk of sarcopenia in Vietnam. In particular, attention to nutrient intake and the management of menopausal symptoms may reduce the risk of sarcopenia.

Surface Modifications of Superparamagnetic Iron Oxide Nanoparticles with Chitosan, Polyethylene Glycol, Polyvinyl Alcohol, and Polyvinylpyrrolidone as Methylene Blue Adsorbent Beads.

Due to the negative impacts the dye may have on aquatic habitats and human health, it is often found in industrial effluent and poses a threat to public health. Hence, to solve this problem, this study developed magnetic adsorbents that can remove synthetic dyes like methylene blue. The adsorbent, in the form of beads, consists of a polymer blend of chitosan, polyethylene glycol, polyvinyl alcohol, polyvinylpyrrolidone, and superparamagnetic iron oxide nanoparticles (average size of 19.03 ± 4.25 nm). The adsorption and desorption of MB from beads were carried out at pH values of 7 and 3.85, respectively. At a concentration of 9 mg/L, the loading capacity and the loading amount of MB after 5 days peaked at 29.75 ± 1.53% and 297.48 ± 15.34 mg/g, respectively. Meanwhile, the entrapment efficiency of MB reached 29.42 ± 2.19% at a concentration of 8 mg/L. The cumulative desorption capacity of the adsorbent after 13 days was at its maximum at 7.72 ± 0.5%. The adsorption and desorption kinetics were evaluated.

Development and Validation of Liquid Chromatographic Method for Fast Determination of Lincomycin, Polymyxin and Vancomycin in Preservation Solution for Transplants.

In this study, a liquid chromatographic method was developed for the fast determination of lincomycin, polymyxin and vancomycin in a preservation solution for transplants. A Kinetex EVO C18 (150 × 4.6 mm, 2.6 µm) column was utilized at 45 °C. Gradient elution was applied using a mixture of mobile phases A and B, both including 30 mM phosphate buffer at pH 2.0 and acetonitrile, at a ratio of 95:5 (v/v) for A and 50:50 (v/v) for B. A flow rate of 1.0 mL/min, an injection volume of 20 µL and UV detection at 210 nm were used. A degradation study treating the three antibiotics with 0.5 M hydrochloric acid, 0.5 M sodium hydroxide and 3% H2O2 indicated that the developed method was selective toward lincomycin, polymyxin, vancomycin and their degradation products. Other ingredients of the preservation solution, like those from the cell culture medium, did not interfere. The method was validated with good sensitivity, linearity, precision and accuracy. Furthermore, lincomycin, polymyxin and vancomycin were found to be stable in this preservation solution for 4 weeks when stored at -20 °C.

A Novel Surgical Landmark to Identify the Recurrent Laryngeal Nerve

Background: Although several surgical landmarks have been proposed to localize the recurrent laryngeal nerve (RLN), there is still no reliable landmark. Aims: To validate the reliability of a novel reference point at the intersection of the inferior border of the cricopharyngeal muscle and the inferior cornu of thyroid cartilage for locating the RLN. Study Design: Cadaver dissection study in the academic department of otolaryngology-head and neck surgery. Methods: Sixty-four RLNs in cadavers were assessed, and measurements of different surgical landmarks in conjunction with the proposed surgical landmark were obtained. Descriptive statistics, Pearson's chi-squared test, and Student's t-test were performed to analyze the data using GraphPad Prism (version 9.4.1; Dotmatics, Boston, Massachusetts, USA). Results: The average distance from the proposed landmark to the RLN was 2.3 ± 0.85 mm. The RLN was located just posterior to the reference point in 95.31% of the cadavers. The RLN passed under the inferior constrictor muscle in 90.63% of the cadavers. There was no statistically significant difference between right- and left-sided RLNs in terms of their relation with the reference point. Conclusion: The proposed reference point can be used as a reliable landmark to locate the RLN. This reference point may help surgeons during difficult thyroidectomy surgeries by providing an additional anatomical landmark.

Fear of Falling: Exploring Associated Factors among Elderly Residents in the Rural Communities of Vietnam.

This research aimed to explore factors associated with the fear of falling (FOF) among community-dwelling older adults in Vietnam. A cross-sectional study was conducted in five communes in Soc Son, Hanoi, Vietnam, from March to June 2017. We recruited a total of 487 participants, which provided sufficient data for analysis. The outcome variable was fear of falling. Several covariates, including demographics, medical history, general health status, geriatric syndromes, eye diseases, assessment of fall risk environment, timed up-and-go test, and number of standing up in 30 s, were collected. A multivariable logistic regression model was performed to determine predictors associated with FOF. The results showed that 54.6% of the participants had FOF. Furthermore, the logistic multivariable regression model revealed several factors associated with FOF among participants in the research sites, including polypharmacy status (OR: 1.79; 95%CI 1.07-2.99), higher scores in quality of life according to the EQ-5D-5L index (OR:6.27; 95%CI: 2.77-14.17), and having fallen during the past 12 months (OR:4.4; 95%CI: 2.39-8.11). These findings contribute to a comprehensive understanding of the intricate relationship between FOF and several associated factors, notably polypharmacy status, quality of life, and having a fall during the past 12 months.

The efficacy and tolerability of proteoglycan F in the treatment of knee osteoarthritis: A prospective, randomized, double-blind controlled trial.

Objective: To identify the efficacy and tolerability of Proteoglycan F in patients with primary knee OA.Design: A 24-week randomized, placebo-controlled, double-blind clinical trial with two arms: (1) Proteoglycan F (received 10 â€‹mg proteoglycan daily, for 24 weeks) and (2) control group (received placebo). Knee symptoms and joint cartilage status (evaluated by ultrasound and MRI of knee joints), quality of life, serum cytokine levels (IL-1ß and TNF-α), and safety evaluation were measured before, during, and after the treatment. Results: After 24-week treatment, pain reduction (in the KOOS pain score) of at least 20% and at least 50% (NRS scale) compared to baseline in the PGF group was significantly higher than those in the control group. The PGF group had greater reductions in the total scores of subchondral bone marrow edema, and bone cocoon under cartilage on knee MRI (classification according to WORMs), which were -2.27 (-4.0; -0.51) and -1.77 (-3.08; -0.46), respectively (p â€‹< â€‹0.05). The two groups had no statistically significant difference in knee ultrasound characteristics. After 4 weeks, 12, and 24 weeks compared to baseline, there was no statistically significant difference in levels of urea, creatinine, aspartate aminotransferase, and alanine aminotransferase within the group and between the two study groups. Conclusions: Salmon cartilage PG with 10 â€‹mg per day has potential to improve pain symptoms and subchondral bone marrow edema and bone cocoon under cartilage lesions in primary knee OA. However, the efficacy of PGF should be viewed with caution, and future studies are needed for more specific evaluation.

Changes in the levels of serum glial fibrillary acidic protein and the correlation with outcomes in severe traumatic brain injury patients.

Purpose: Glial fibrillary acidic protein serves as a biomarker indicative of astroglial injury, particularly following instances of severe traumatic brain injury. This study aims to evaluate variations in serum glial fibrillary acidic protein levels within the first 3 days and their correlation with outcomes in patients with severe traumatic brain injury. Subjects and methods: Thirty-nine patients with severe traumatic brain injury were enrolled in the study. Their blood samples were collected at six distinct time points: T0 (upon admission), T1, T2, T3, T4, and T5 (6-, 12-, 24-, 48-, and 72-h post-admission, respectively). The blood samples were run for the quantification of serum glial fibrillary acidic protein levels and other biochemical tests. All patients were closely watched and the outcomes at discharge were evaluated. Results: Glial fibrillary acidic protein levels tend to increase gradually from the time of admission to 48 h post-admission and then decrease at 72 h post-admission. Glial fibrillary acidic protein T2 is correlated with Acute Physiology and Chronic Health Evaluation II score, lactate, Simplified Acute Physiology Score II score and outcome. Glial fibrillary acidic protein max correlated with lactate, Acute Physiology and Chronic Health Evaluation II score, Simplified Acute Physiology Score II score, and outcome. Glasgow Coma Score at admission and glial fibrillary acidic protein T2 (OR = 1.034; p = 0.025), T3 (OR = 1.029; p = 0.046), T4 (OR = 1.006; p = 0.032), T5 (OR = 1.012; p = 0.048) and glial fibrillary acidic protein max (OR = 1.005; p = 0.010) were independent factors that have significant prognostic value in mortality in patients with severe traumatic brain injury. The predictive model in predicting mortality had the highest area under the curve based on glial fibrillary acidic protein T2 and Glasgow Coma Score T0 with an area under the curve of 0.904 and p < 0.001. In the multivariable regression model, glial fibrillary acidic protein max was associated with Glasgow score (p < 0.001; VIF = 1.585), lactate T0 (p = 0.024; VIF = 1.163), Acute Physiology and Chronic Health Evaluation II score (p = 0.037; VIF = 1.360), and Rotterdam score (p = 0.044; VIF = 1.713). Conclusion: Glial fibrillary acidic protein levels tend to increase gradually from the time of admission to 48 h post-admission then decreases at 72 h post-admission. Glial fibrillary acidic protein T2, T3, T4, T5, and glial fibrillary acidic protein max were independent factors with significant prognostic mortality values in patients with severe traumatic brain injury.

Analysis of Hospitals Switching From a "Danger to Self" Question to Universal Columbia-Suicide Severity Rating Scale Screening: Impact on Screenings, Identification of Suicide Risk, and Documented Psychiatric Care.

Objective: Sutter Health launched system-wide general population standardized suicide screening with the Columbia-Suicide Severity Rating Scale (C-SSRS) screen (triage) version in 23 hospitals in 2019, replacing a one-question "danger to self" (DTS) assessment. This study analyzed the impact of C-SSRS implementation on screening rates, positive screenings, and documented psychiatric care within 90 days for all patients and a subgroup diagnosed with Major Depressive Disorder (MDD). Methods: Adults seen at hospitals in the pre-period (July 1, 2017-June 30, 2019) and post-period (July 1, 2019-December 31, 2020) were identified using electronic health records. Outcomes were compared using chi-square statistics and interrupted time series (ITS) models. Results: Pre-period, 92.8% (740,984/798,653) of patients were screened by DTS versus 84.6% (504,015/595,915) by C-SSRS in the post-period. Positive screening rates were 1.5% pre-period and 2.2% post-period, and 9.2% pre-period versus 10.8% post-period for those with MDD. Among individuals with positive screenings, 64.0% (pre-period) had documented follow-up psychiatric care versus 52.5% post-period and 66.4% of those with moderate or high-risk. Among all patients seen there was an overall increase in documentation of psychiatric care within 90 days (0.87% pre- to 0.96% post-period). ITS models revealed a 9.6% decline in screening, 1.3% increase in positive screenings, and 12.9% decline in documented psychiatric care following C-SSRS implementation (all p < 0.01). Conclusions: Following implementation, there was meaningful increase in suicide risk identification, and an increase in the proportion of patients with documented psychiatric care. Observed relative declines in screening warrant future research examining opportunities and barriers to general population C-SSRS use.

Fusobacterium nucleatum infection modulates the transcriptome and epigenome of HCT116 colorectal cancer cells in an oxygen-dependent manner.

Fusobacterium nucleatum, a gram-negative oral bacterium, has been consistently validated as a strong contributor to the progression of several types of cancer, including colorectal (CRC) and pancreatic cancer. While previous in vitro studies have shown that intracellular F. nucleatum enhances malignant phenotypes such as cell migration, the dependence of this regulation on features of the tumor microenvironment (TME) such as oxygen levels are wholly uncharacterized. Here we examine the influence of hypoxia in facilitating F. nucleatum invasion and its effects on host responses focusing on changes in the global epigenome and transcriptome. Using a multiomic approach, we analyze epigenomic alterations of H3K27ac and global transcriptomic alterations sustained within a hypoxia and normoxia conditioned CRC cell line HCT116 at 24 h following initial infection with F. nucleatum. Our findings reveal that intracellular F. nucleatum activates signaling pathways and biological processes in host cells similar to those induced upon hypoxia conditioning in the absence of infection. Furthermore, we show that a hypoxic TME favors F. nucleatum invasion and persistence and therefore infection under hypoxia may amplify malignant transformation by exacerbating the effects induced by hypoxia alone. These results motivate future studies to investigate host-microbe interactions in tumor tissue relevant conditions that more accurately define parameters for targeted cancer therapies.

Photorefractivity and photocurrent dynamics of triphenylamine-based polymer composites.

The photorefractive properties of triphenylamine polymer-based composites with various composition ratios were investigated via optical diffraction, response time, asymmetric energy transfer, and transient photocurrent. The composite consisted of a photoconductive polymer of poly((4-diphenylamino)benzyl acrylate), a photoconductive plasticizer of (4-diphenylamino)phenyl)methanol, a sensitizer of [6,6]-phenyl-C61-butyric acid methyl ester, and a nonlinear optical dye of (4-(azepan-1-yl)-benzylidene)malononitrile. The photorefractive properties and related quantities were dependent on the composition, which was related to the glass transition temperature of the photorefractive polymers. The quantum efficiency (QE) of photocarrier generation was evaluated from the initial slope of the transient photocurrent. Transient photocurrents were measured and showed two unique peaks: one in the range of 10-4 to 10-3 s and the other in the range of 10-1 to 1 s. The transient photocurrents was well simulated (or reproduced) by the expanded two-trapping site model with two kinds of photocarrier generation and recombination processes and two different trapping sites. The obtained photorefractive quantity of trap density was significantly related to the photoconductive parameters of QE.

AMRViz enables seamless genomics analysis and visualization of antimicrobial resistance.

We have developed AMRViz, a toolkit for analyzing, visualizing, and managing bacterial genomics samples. The toolkit is bundled with the current best practice analysis pipeline allowing researchers to perform comprehensive analysis of a collection of samples directly from raw sequencing data with a single command line. The analysis results in a report showing the genome structure, genome annotations, antibiotic resistance and virulence profile for each sample. The pan-genome of all samples of the collection is analyzed to identify core- and accessory-genes. Phylogenies of the whole genome as well as all gene clusters are also generated. The toolkit provides a web-based visualization dashboard allowing researchers to interactively examine various aspects of the analysis results. Availability: AMRViz is implemented in Python and NodeJS, and is publicly available under open source MIT license at https://github.com/amromics/amrviz .

Blood volume reduction due to rapid plasma loss after birth in preterm piglets.

BACKGROUND: Understanding changes in blood volume after preterm birth is critical to preventing cardiovascular deterioration in preterm infants. The aims were to determine if blood volume is higher in preterm than term piglets and if blood volume changes in the hours after birth. METHODS: Paired blood volume measurements were conducted in preterm piglets (98/115d gestation, ~28wk gestation infant) at 0.5-5 h (n = 12), 0.5-9 h (n = 44) and 5-11 h (n = 7) after birth, and in a term cohort at 0.5-9 h (n = 40) while under intensive care. RESULTS: At 30 min after birth, blood volume was significantly lower in preterm piglets compared to term piglets. By 9 h after birth, blood volume had reduced by 18% in preterm piglets and 13% in term piglets. By 5-9 h after birth, preterm piglets had significantly lower blood volumes than at term (61 ± 10 vs. 76 ± 11 mL/kg). CONCLUSIONS: In contrast to clinical resources, preterm piglets have a lower blood volume than at term. Substantial reductions in blood volume after birth leave some preterm piglets hypovolemic. If this also occurs in preterm infants, this may have important clinical consequences. Modern studies of blood volume changes after birth are essential for improving preterm outcomes. IMPACT: Preterm piglets do not have a higher blood volume than their term counterparts, in contrast to current clinical estimates. Rapid reduction in blood volume after birth leads to hypovolemia in some preterm piglets. There is a critical need to understand blood volume changes after birth in preterm infants in order to improve clinical management of blood volume.

Tigilanol tiglate is an oncolytic small molecule that induces immunogenic cell death and enhances the response of both target and non-injected tumors to immune checkpoint blockade.

BACKGROUND: Tigilanol tiglate (TT) is a protein kinase C (PKC)/C1 domain activator currently being developed as an intralesional agent for the treatment of various (sub)cutaneous malignancies. Previous work has shown that intratumoral (I.T.) injection of TT causes vascular disruption with concomitant tumor ablation in several preclinical models of cancer, in addition to various (sub)cutaneous tumors presenting in the veterinary clinic. TT has completed Phase I dose escalation trials, with some patients showing signs of abscopal effects. However, the exact molecular details underpinning its mechanism of action (MoA), together with its immunotherapeutic potential in oncology remain unclear. METHODS: A combination of microscopy, luciferase assays, immunofluorescence, immunoblotting, subcellular fractionation, intracellular ATP assays, phagocytosis assays and mixed lymphocyte reactions were used to probe the MoA of TT in vitro. In vivo studies with TT used MM649 xenograft, CT-26 and immune checkpoint inhibitor refractory B16-F10-OVA tumor bearing mice, the latter with or without anti-programmed cell death 1 (PD-1)/anti-cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) mAb treatment. The effect of TT at injected and non-injected tumors was also assessed. RESULTS: Here, we show that TT induces the death of endothelial and cancer cells at therapeutically relevant concentrations via a caspase/gasdermin E-dependent pyroptopic pathway. At therapeutic doses, our data demonstrate that TT acts as a lipotoxin, binding to and promoting mitochondrial/endoplasmic reticulum (ER) dysfunction (leading to unfolded protein responsemt/ER upregulation) with subsequent ATP depletion, organelle swelling, caspase activation, gasdermin E cleavage and induction of terminal necrosis. Consistent with binding to ER membranes, we found that TT treatment promoted activation of the integrated stress response together with the release/externalization of damage-associated molecular patterns (HMGB1, ATP, calreticulin) from cancer cells in vitro and in vivo, characteristics indicative of immunogenic cell death (ICD). Confirmation of ICD in vivo was obtained through vaccination and rechallenge experiments using CT-26 colon carcinoma tumor bearing mice. Furthermore, TT also reduced tumor volume, induced immune cell infiltration, as well as improved survival in B16-F10-OVA tumor bearing mice when combined with immune checkpoint blockade. CONCLUSIONS: These data demonstrate that TT is an oncolytic small molecule with multiple targets and confirms that cell death induced by this compound has the potential to augment antitumor responses to immunotherapy.

In Situ Synthesis and Self-Assembly of Peptide-PEG Conjugates: A Facile Method for the Construction of Fibrous Hydrogels.

Peptide-based hydrogels have gained considerable attention as a compelling platform for various biomedical applications in recent years. Their attractiveness stems from their ability to seamlessly integrate diverse properties, such as biocompatibility, biodegradability, easily adjustable hydrophilicity/hydrophobicity, and other functionalities. However, a significant drawback is that most of the functional self-assembling peptides cannot form robust hydrogels suitable for biological applications. In this study, we present the synthesis of novel peptide-PEG conjugates and explore their comprehensive hydrogel properties. The hydrogel comprises double networks, with the first network formed through the self-assembly of peptides to create a ß-sheet secondary structure. The second network is established through covalent bond formation via N-hydroxysuccinimide chemistry between peptides and a 4-arm PEG to form a covalently linked network. Importantly, our findings reveal that this hydrogel formation method can be applied to other peptides containing lysine-rich sequences. Upon encapsulation of the hydrogel with antimicrobial peptides, the hydrogel retained high bacterial killing efficiency while showing minimum cytotoxicity toward mammalian cells. We hope that this method opens new avenues for the development of a novel class of peptide-polymer hydrogel materials with enhanced performance in biomedical contexts, particularly in reducing the potential for infection in applications of tissue regeneration and drug delivery.

Lifestyle interventions with dietary strategies after breast cancer diagnosis: a systematic review.

PURPOSE: Obesity can increase mortality and morbidity in breast cancer survivors. Healthy lifestyle factors such as diet can help manage weight in this population. This systematic review examined lifestyle interventions with dietary strategies for breast cancer survivors and their effect on diet and/or weight-related outcomes. METHODS: Searches were conducted in Ovid MEDLINE® ALL (1946-February 14, 2022), Embase (Elsevier), CINAHL Complete (EBSCO), and APA PsycArticles (EBSCO), using keywords for diet, breast cancer, and intervention. The search was limited to human studies, English language, and publication processing date 2016-2023. RESULTS: The search yielded 3427 articles. After title and abstract review, 225 full-text articles were screened, and 67 articles with 61 distinct samples and interventions met inclusion criteria. Of these 61 lifestyle interventions with dietary strategies, 43 interventions also addressed physical activity. Most studies were randomized controlled trials (n = 41) and conducted post-treatment (n = 45). Mean participant age was 54 years. Of 29 studies that reported race/ethnicity, 20 (69%) reported ≥50% White participants. Of 36 that reported dietary outcomes, 29 (81%) reported significant findings. Of 57 that reported weight-related outcomes, 51 (89%) reported significant findings. CONCLUSION: This review demonstrated promising evidence for the efficacy of lifestyle interventions with dietary strategies in breast cancer survivors. However, culturally tailored interventions and interventions conducted before and during treatment are lacking.

Two DOT1 enzymes cooperatively mediate efficient ubiquitin-independent histone H3 lysine 76 tri-methylation in kinetoplastids.

In higher eukaryotes, a single DOT1 histone H3 lysine 79 (H3K79) methyltransferase processively produces H3K79me2/me3 through histone H2B mono-ubiquitin interaction, while the kinetoplastid Trypanosoma brucei di-methyltransferase DOT1A and tri-methyltransferase DOT1B efficiently methylate the homologous H3K76 without H2B mono-ubiquitination. Based on structural and biochemical analyses of DOT1A, we identify key residues in the methyltransferase motifs VI and X for efficient ubiquitin-independent H3K76 methylation in kinetoplastids. Substitution of a basic to an acidic residue within motif VI (Gx6K) is essential to stabilize the DOT1A enzyme-substrate complex, while substitution of the motif X sequence VYGE by CAKS renders a rigid active-site loop flexible, implying a distinct mechanism of substrate recognition. We further reveal distinct methylation kinetics and substrate preferences of DOT1A (H3K76me0) and DOT1B (DOT1A products H3K76me1/me2) in vitro, determined by a Ser and Ala residue within motif IV, respectively, enabling DOT1A and DOT1B to mediate efficient H3K76 tri-methylation non-processively but cooperatively, and suggesting why kinetoplastids have evolved two DOT1 enzymes.