Inheritable Silencing of Endogenous Genes by Hit-and-Run Targeted Epigenetic Editing.

Gene silencing is instrumental to interrogate gene function and holds promise for therapeutic applications. Here, we repurpose the endogenous retroviruses' silencing machinery of embryonic stem cells to stably silence three highly expressed genes in somatic cells by epigenetics. This was achieved by transiently expressing combinations of engineered transcriptional repressors that bind to and synergize at the target locus to instruct repressive histone marks and de novo DNA methylation, thus ensuring long-term memory of the repressive epigenetic state. Silencing was highly specific, as shown by genome-wide analyses, sharply confined to the targeted locus without spreading to nearby genes, resistant to activation induced by cytokine stimulation, and relieved only by targeted DNA demethylation. We demonstrate the portability of this technology by multiplex gene silencing, adopting different DNA binding platforms and interrogating thousands of genomic loci in different cell types, including primary T lymphocytes. Targeted epigenome editing might have broad application in research and medicine.

Warming-induced tree growth may help offset increasing disturbance across the Canadian boreal forest.

Large projected increases in forest disturbance pose a major threat to future wood fiber supply and carbon sequestration in the cold-limited, Canadian boreal forest ecosystem. Given the large sensitivity of tree growth to temperature, warming-induced increases in forest productivity have the potential to reduce these threats, but research efforts to date have yielded contradictory results attributed to limited data availability, methodological biases, and regional variability in forest dynamics. Here, we apply a machine learning algorithm to an unprecedented network of over 1 million tree growth records (1958 to 2018) from 20,089 permanent sample plots distributed across both Canada and the United States, spanning a 16.5 °C climatic gradient. Fitted models were then used to project the near-term (2050 s time period) growth of the six most abundant tree species in the Canadian boreal forest. Our results reveal a large, positive effect of increasing thermal energy on tree growth for most of the target species, leading to 20.5 to 22.7% projected gains in growth with climate change under RCP 4.5 and 8.5. The magnitude of these gains, which peak in the colder and wetter regions of the boreal forest, suggests that warming-induced growth increases should no longer be considered marginal but may in fact significantly offset some of the negative impacts of projected increases in drought and wildfire on wood supply and carbon sequestration and have major implications on ecological forecasts and the global economy.

Fewer systematic prostate core biopsies in clinical stage T1c prostate cancer leads to biochemical recurrence after brachytherapy as monotherapy.

BACKGROUND: After brachytherapy, fewer prostate biopsy cores at diagnosis can underestimate the pathological characteristics of prostate cancer (PCa) with lower concordance, resulting in improper treatment, particularly in patients with low-risk nonpalpable cT1c PCa. The aim of this study was to assess the relationship between the number of biopsy cores at diagnosis and long-term clinical outcomes after brachytherapy for cT1c PCa. METHODS: We reviewed 516 patients with localized cT1c PCa with Gleason scores of 3 + 3 = 6 or 3 + 4 = 7 who underwent brachytherapy as monotherapy without hormonal therapy between January 2005 and September 2014 at our institution. Clinical staging was based on the American Joint Committee on Cancer manual for staging. Thus, the cT1c category is based solely on digital rectal examination. The primary outcome was biochemical recurrence (BCR). Based on the optimized cutoff value for biopsy core number obtained from receiver operating characteristic analysis, patients were divided into the biopsy cores ≤8 (N = 123) and ≥9 (N = 393) groups. The BCR-free survival rate was compared between the groups. Prognostic factors for BCR were evaluated, including age, initial prostate-specific antigen (PSA) level, Gleason score, positive core rate, PSA density, prostate magnetic resonance imaging findings, and biopsy core number. RESULTS: The median patient age was 66.0 years (interquartile range [IQR]: 61.0-71.0 years), and the median follow-up time was 11.1 years (IQR: 9.5-13.3 years). The median number of core biopsies was 12 (IQR: 9-12). The area under the curve was 0.637 (95% confidence interval [CI]: 0.53-0.75), and the optimal biopsy core cutoff value for BCR prediction was 8.5 (sensitivity = 43.5%, specificity = 77.1%). Although fewer patients had Gleason scores of 3 + 4 = 7 (19/123 [15%] vs. 125/393 [32%], p < 0.02) in the biopsy cores ≤8 group, the 10-year BCR-free survival rate was significantly lower in the biopsy cores ≤8 group than in the biopsy cores ≥9 group (93.8% vs. 96.3%, p < 0.05). Multivariate analysis revealed that a lower biopsy core number (hazard ratio: 0.828, 95% CI: 0.71-0.97, p < 0.03) and a Gleason score of 3 + 4 = 7 (hazard ratio: 3.26, 95% CI: 1.37-7.73, p < 0.01) significantly predicted BCR. CONCLUSIONS: A low number of prostate core biopsies results in worse BCR-free survival after brachytherapy as monotherapy in patients with cT1c PCa.

Unraveling Exchange Coupling in Ferrites Nano-Heterostructures.

The magnetic coupling of a set of SrFe12 O19 /CoFe2 O4 nanocomposites is investigated. Advanced electron microscopy evidences the structural coherence and texture at the interfaces of the nanostructures. The fraction of the lower anisotropy phase (CoFe2 O4 ) is tuned to assess the limits that define magnetically exchange-coupled interfaces by performing magnetic remanence, first-order reversal curves (FORCs), and relaxation measurements. By combining these magnetometry techniques and the structural and morphological information from X-ray diffraction, electron microscopy, and Mössbauer spectrometry, the exchange intergranular interaction is evidenced, and the critical thickness within which coupled interfaces have a uniform reversal unraveled.

Detection of anaerobic and aerobic bacteria from commercial tattoo and permanent makeup inks.

Tattooing and use of permanent makeup (PMU) have dramatically increased over the last decade, with a concomitant increase in ink-related infections. Studies have shown evidence that commercial tattoo and PMU inks are frequently contaminated with pathogenic microorganisms. Considering that tattoo inks are placed into the dermal layer of the skin where anaerobic bacteria can thrive and cause infections in low-oxygen environments, the prevalence of anaerobic and aerobic bacteria should be assessed in tattoo and PMU inks. In this study, we tested 75 tattoo and PMU inks using the analytical methods described in the FDA Bacteriological Analytical Manual Chapter 23 for the detection of both aerobic and anaerobic bacterial contamination, followed by 16S rRNA gene sequencing for microbial identification. Of 75 ink samples, we found 26 contaminated samples with 34 bacterial isolates taxonomically classified into 14 genera and 22 species. Among the 34 bacterial isolates, 19 were identified as possibly pathogenic bacterial strains. Two species, namely Cutibacterium acnes (four strains) and Staphylococcus epidermidis (two strains) were isolated under anaerobic conditions. Two possibly pathogenic bacterial strains, Staphylococcus saprophyticus and C. acnes, were isolated together from the same ink samples (n = 2), indicating that tattoo and PMU inks can contain both aerobic (S. saprophyticus) and anaerobic bacteria (C. acnes). No significant association was found between sterility claims on the ink label and the absence of bacterial contamination. The results indicate that tattoo and PMU inks can also contain anaerobic bacteria. IMPORTANCE: The rising popularity of tattooing and permanent makeup (PMU) has led to increased reports of ink-related infections. This study is the first to investigate the presence of both aerobic and anaerobic bacteria in commercial tattoo and PMU inks under aerobic and anaerobic conditions. Our findings reveal that unopened and sealed tattoo inks can harbor anaerobic bacteria, known to thrive in low-oxygen environments, such as the dermal layer of the skin, alongside aerobic bacteria. This suggests that contaminated tattoo inks could be a source of infection from both types of bacteria. The results emphasize the importance of monitoring these products for both aerobic and anaerobic bacteria, including possibly pathogenic microorganisms.

Enhancing Intrinsic Magnetic Hardness by Modulating Antagonistic Interactions in the Rare-Earth-Free Magnetic Solid Solution Hf2 Fe1-δ Ru5-x Irx+δ B2.

The quinary members in the solid solution Hf2 Fe1-δ Ru5-x Irx+δ B2 (x=1-4, VE=63-66) have been investigated experimentally and computationally. They were synthesized via arc-melting and analyzed by EDX and X-ray diffraction. Density functional theory (DFT) calculations predicted a preference for magnetic ordering in all members, but with a strong competition between ferro- and antiferromagnetism arising from interchain Fe-Fe interactions. The spin exchange and magnetic anisotropy energies predicted the lowest magnetic hardness for x=1 and 3 and the highest for x=2. Magnetization measurements confirm the DFT predictions and demonstrate that the antiferromagnetic ordering (TN =55-70 K) found at low magnetic fields changed to ferromagnetic (TC =150-750 K) at higher fields, suggesting metamagnetic behavior for all samples. As predicted, Hf2 FeRu3 Ir2 B2 has the highest intrinsic coercivity (Hc =74 kA/m) reported to date for Ti3 Co5 B2 -type phases. Furthermore, all coercivities outperform that of ferromagnetic Hf2 FeIr5 B2 , indicating the importance of AFM interactions in enhancing magnetic anisotropy in these materials. Importantly, two members (x=1 and 4) maintain intrinsic coercivities in the semi-hard range at room temperature. This study opens an avenue for controlling magnetic hardness by modulating antagonistic AFM and FM interactions in low-dimensional rare-earth-free magnetic materials.

Changes in Medication Utilization and Adherence Associated with Homeless Adults' Entry into Permanent Supportive Housing.

BACKGROUND: Permanent supportive housing (PSH) programs, which have grown over the last decade, have been associated with changes in health care utilization and spending. However, little is known about the impact of such programs on use of prescription drugs critical for managing chronic diseases prevalent among those with unstable housing. OBJECTIVE: To evaluate the effects of PSH on medication utilization and adherence among Medicaid enrollees in Pennsylvania. DESIGN: Difference-in-differences study comparing medication utilization and adherence between PSH participants and a matched comparison cohort from 7 to 18 months before PSH entry to 12 months post PSH entry. SUBJECTS: Pennsylvania Medicaid enrollees (n = 1375) who entered PSH during 2011-2016, and a propensity-matched comparison cohort of 5405 enrollees experiencing housing instability who did not receive PSH but received other housing services indicative of episodic or chronic homelessness (e.g., emergency shelter stays). MAIN MEASURES: Proportion with prescription fill, mean proportion of days covered (PDC), and percent adherent (PDC ≥ 80%) for antidepressants, antipsychotics, anti-asthmatics, and diabetes medications. KEY RESULTS: The PSH cohort saw a 4.77% (95% CI 2.87% to 6.67%) relative increase in the proportion filling any prescription, compared to the comparison cohort. Percent adherent among antidepressant users in the PSH cohort rose 7.41% (95% CI 0.26% to 14.57%) compared to the comparison cohort. While utilization increased in the other medication classes among the PSH cohort, differences from the comparison cohort were not statistically significant. CONCLUSIONS: PSH participation is associated with increases in filling prescription medications overall and improved adherence to antidepressant medications. These results can inform state and federal policy to increase PSH placement among Medicaid enrollees experiencing homelessness.

Development and validation of a nomogram for preoperatively predicting permanent stoma after rectal cancer surgery with ileostomy: a retrospective cohort study.

BACKGROUND: For patients with rectal cancer, the utilization of temporary ileostomy (TI) has proven effective in minimizing the occurrence of severe complications post-surgery, such as anastomotic leaks; however, some patients are unable to reverse in time or even develop a permanent stoma (PS). We aimed to determine the preoperative predictors associated with TS failure and develop and validate appropriate predictive models to improve patients' quality of life. METHODS: This research included 403 patients with rectal cancer who underwent temporary ileostomies between January 2017 and December 2021. All patients were randomly divided into either the developmental (70%) or validation (30%) group. The independent risk factors for PS were determined using univariate and multivariate logistic regression analyses. Subsequently, a nomogram was constructed, and the prediction probability was estimated by calculating the area under the curve (AUC) using receiver operating characteristic (ROC) analysis. A calibration plot was used to evaluate the nomogram calibration. RESULTS: Of the 403 enrolled patients, 282 were randomized into the developmental group, 121 into the validation group, and 58 (14.39%) had a PS. The development group consisted of 282 patients, of whom 39 (13.81%) had a PS. The validation group consisted of 121 patients, of whom, 19 (15.70%) had a PS; 37 related factors were analyzed in the study. Multivariate logistic regression analysis demonstrated significant associations between the occurrence of PS and various factors in this patient cohort, including tumor location (OR = 6.631, P = 0.005), tumor markers (OR = 2.309, P = 0.035), American Society of Anesthesiologists (ASA) score (OR = 4.784, P = 0.004), T4 stage (OR = 2.880, P = 0.036), lymph node metastasis (OR = 4.566, P = 0.001), and distant metastasis (OR = 4.478, P = 0.036). Furthermore, a preoperative nomogram was constructed based on these data and subsequently validated in an independent validation group. CONCLUSION: We identified six independent preoperative risk factors associated with PS following rectal cancer resection and developed a validated nomogram with an area under the ROC curve of 0.7758, which can assist surgeons in formulating better surgical options, such as colostomy, for patients at high risk of PS.

New craniodental fossils of Paranthropus robustus from Kromdraai, South Africa (2014-2017 excavations).

Since the initial discovery of Paranthropus robustus at the site of Kromdraai in 1938, the hypodigm of this species has been expanded by subsequent work at the localities of Swartkrans and Drimolen, with a few fossils also known from Cooper's D, Gondolin and Sterkfontein Member 5. Beginning in 2014, systematic excavations at Kromdraai uncovered a large and previously unknown fossiliferous area, shedding light on Units O and P in the earliest part of the site's stratigraphic sequence. The aim of this paper is to provide detailed descriptions and illustrations of 30 P. robustus craniodental specimens recovered between 2014 and 2017 within the Unit P deposits at Kromdraai. This new sample predates all prior conspecific specimens found at this site (including the holotype of P. robustus from Kromdraai, TM 1517). Its basic dental morphology dimensions and cranial features are compared in a preliminary analysis with other P. robustus samples. The P. robustus sample from Kromdraai Unit P documents previously unknown portions of the P. robustus juvenile cranium. The new dental and cranial remains aid in the exploration of potential morphological distinctions between site-specific P. robustus samples and are compared favorably in size and morphology with the small P. robustus specimens from Drimolen (e.g., DNH 7). These findings do not support the hypothesis that the specimens from Drimolen belong to a different taxonomic group. Instead, they reinforce the presence of a significant degree of sexual dimorphism within P. robustus. The Kromdraai Unit P specimens also contribute to the biodemographic profile of P. robustus. The notable prevalence of infants (i.e., juvenile individuals before the emergence of their first permanent molars) mirrors the natural mortality profiles observed in wild chimpanzees. This suggests a closer resemblance in the processes of accumulation in Kromdraai Unit P and Drimolen than at Swartkrans.

Reconsidering the Role of Frozen Section in Sentinel Lymph Node Biopsy for Mastectomy Patients.

INTRODUCTION: Axillary lymph node dissection was recommended for mastectomy patients with more than two nodal metastases from sentinel lymph node biopsy. Conventionally, intraoperative frozen section was sent routinely to reduce the need for second-stage axillary lymph node dissection; however, recent global trend has seen decreasing usage of the intraoperative analyses. This pilot study conducted in Thailand aimed to evaluate the role of intraoperative frozen section of sentinel lymph node biopsy in early-stage breast cancer patients who underwent mastectomy. METHODS: A 5-y retrospective study of 1773 patients was conducted in Thailand. The inclusion criteria were early-stage breast cancer patients with either radiologically negative nodes, or radiographically borderline nodes found to be negative on fine needle aspiration who underwent mastectomy and sentinel lymph node biopsy. Reoperations were indicated when three or more nodal metastases were detected on the pathological analysis. The reoperation rate prevented by frozen section and the reoperation rate needed for those with permanent section alone were reported. RESULTS: Among 265 patients, 202 patients underwent concomitant intraoperative frozen section while the remaining 63 patients underwent permanent section alone. Six patients (3.0%) from the frozen section group and one patient (1.6%) from the permanent section group were found with more than two nodal metastases. Despite using intraoperative frozen sections, only one patient from each group required reoperation. There was no significant difference in the number of patients requiring reoperation between the frozen section group and the permanent section group. CONCLUSIONS: Our study provides strong evidence to all surgeons that in early breast cancer patients undergoing mastectomy, sentinel lymph node biopsy with permanent section analysis alone may not lower the standard of care compared to using additional intraoperative frozen section analysis. Adopting this practice may lead to decreased operation costs, operative time, and anesthetic side effects.

The quality of reporting in case reports of permanent neonatal diabetes mellitus: a cross-sectional study.

BACKGROUND: Although randomized trials and systematic reviews provide the best evidence to guide medical practice, many permanent neonatal diabetes mellitus (PNDM) studies have been published as case reports. However, the quality of these studies has not been assessed. The purpose of this study was to assess the extent to which the current case reports for PNDM comply with the Case Report (CARE) guidelines and to explore variables associated with the reporting. METHOD: Six English and four Chinese databases were searched from their inception to December 2022 for PNDM case reports. The 23 items CARE checklist was used to measure reporting quality. Primary outcome was the adherence rate of each CARE item and second outcome was total reporting score for each included PNDM case report. Linear and logistic regression analyses were used to examine the connection between five pre-specified predictor variables and the reporting quality. The predictor variables were impact factor of the published journal (<3.4 vs. ≥3.4, categorized according to the median), funding (yes vs. no), language (English vs. other language), published journal type (general vs. special) and year of publication (>2013 vs. ≤ 2013). RESULT: In total, 105 PNDM case reports were included in this study. None of the 105 PNDM case reports fulfilled all 23 items of the CARE checklist. The response rate of 11 items were under 50%, including prognostic characteristics presentation (0%), patient perspective interpretation (0%), diagnostic challenges statement (2.9%), clinical course summary (21.0%), diagnostic reasoning statement (22.9%), title identification (24.8%), case presentation (33.3%), disease history description (34.3%), strengths and limitations explanation (41.0%), informed consent statement (45.7%), and lesson elucidation (47.6%). This study identified that the PNDM case reports published in higher impact factor journals were statistically associated with a higher reporting quality. CONCLUSION: The reporting of case reports for PNDM is generally poor. As a result, this information may be misleading to providers, and the clinical applications may be detrimental to patient care. To improve reporting quality, journals should encourage strict adherence to the CARE guidelines.

Therapeutic effect of intraperitoneal dexamethasone on noise-induced permanent threshold shift in mice model.

The purpose of the study was to which investigate whether dexamethasone, which has anti-inflammatory and immune response suppression roles, could treat noise-induced hearing loss caused by damage to hair cells in the cochlea. The experiment used 8-week-old CBA mice exposed to white noise at an intensity of 110 dB SPL for 2 h, with hearing loss confirmed by the auditory brainstem response test. Dexamethasone was administered by intraperitoneal injection for 5 days, and the therapeutic effect was investigated for 3 weeks. The experimental groups were 3 mg/kg of dexamethasone (3 mpk) and 10 mg/kg of dexamethasone (10 mpk), and the control group was a saline-administered group. The results showed that compared to the control group, the hearing threshold value was recovered by 10 dB SPL compared to the saline group from the 14th day in the 3 mpk group. In the 10 mpk group, thresholds were recovered from the 7th day compared to the saline group. This difference was similar at 4 kHz, and in the case of the 10 mpk group, the threshold was recovered by 20 dB SPL compared to the saline group. The study also confirmed the restoration of nerve cell activity and showed a recovery effect of about 20 µV in the amplitude value change in the 10 mpk group. In conclusion, the study suggests that dexamethasone has a therapeutic effect for noise-induced hearing loss by increasing the activity of nerve cells and showing a recovery effect from hair cells damaged by noise.

Tuning the magnetic properties of hard-soft Ba0.5Sr0.5Fe10Al2O19and Ni0.1Co0.9Fe2O4nanocomposites via one pot sol-gel auto combustion method for permanent magnet applications.

Permanent magnets generate magnetic fields that can be sustained when a reverse field is supplied. These permanent magnets are effective in a wide range of applications. However, strategic rare-earth element demand has increased interest in replacing them with huge energy product (BH)max. Exchange-coupled hard/soft ferrite nanocomposites have the potential to replace a portion of extravagant rare earth element-based magnets. In the present, we have reported the facile auto combustion synthesis of exchange-coupled Ba0.5Sr0.5Fe10Al2O19and Ni0.1Co0.9Fe2O4nanocomposites by increasing the content of soft ferrite over the hard fromx= 0.1 to 0.4 wt%. The XRD combined with Rietveld analysis reflected the presence of hexaferrite and spinel ferrite without the existence of secondary phases. The absorption bands from the Fourier transform infrared spectrum analysis proved the presence of M-O bonds in tetrahedral sites and octahedral sites. Rod and non-spherical images from TEM represent the hexaferrite and spinel ferrite. The smoothM-Hcurve and a single peak of the switching field distribution curve prove that the material has undergone a good exchange coupling. The nanopowders displayed an increase in saturation magnetization and a decrease in coercivity with the increases in the spinel content. The prepared nanocomposites were showing higher energy products. The composite with the ratiox= 0.2 displayed a higher value of (BH)maxof 13.16 kJ m-3.

Pacemaker-Related Factors and Outcomes of Fontan Patients　- Impact of Paced QRS Duration.

BACKGROUND: Permanent pacemaker (PPM) implantation has been identified as a risk factor for morbidity and mortality after Fontan operation. This study investigated the factors associated with outcomes in patients with Fontan physiology who underwent PPM implantation. METHODS AND RESULTS: We retrospectively reviewed 508 patients who underwent Fontan surgery at Asan Medical Center between September 1992 and August 2022. Of these patients, 37 (7.3%) received PPM implantation. Five patients were excluded, leaving 32 patients, of whom 11 were categorized into the poor outcome group. Poor outcomes comprised death, heart transplantation, and "Fontan failure". Clinical, Fontan procedure-related, and PPM-related factors were compared between the poor and good outcome groups. Ventricular morphology, Fontan procedure-associated factors, pacing mode, high ventricular pacing rate, and time from first arrhythmia to PPM implantation did not differ significantly between the 2 groups. However, the poor outcome group exhibited a significantly longer mean paced QRS duration (P=0.044). Receiver operating characteristic curve analysis revealed a paced QRS duration cut-off value of 153 ms with an area under the curve of 0.73 (P=0.035). CONCLUSIONS: A longer paced QRS duration was associated with poor outcomes, indicating its potential to predict adverse outcomes among Fontan patients.

Identification of the pigments used in permanent makeup and their ability to elicit allergic contact dermatitis.

BACKGROUND: Decorative tattoos are known to contain ingredients that may elicit allergic contact dermatitis; it is less well-known if permanent makeup pigments carry the same risk. OBJECTIVE: Identify pigments used in permanent makeup inks sold in the United States and review cases of allergic contact dermatitis to these pigments. METHODS: Using internet searches, permanent makeup inks sold in the United States were identified. Safety data sheets were used to catalog pigments used in permanent makeup. A subsequent literature search was performed to identify cases of allergic contact dermatitis to these pigments. RESULTS: A total of 974 permanent makeup inks were reviewed, and 79 unique pigments were identified. The average product contained 4 pigments. Twenty of the pigments were inorganic metals, including carbon, iron, chromium, manganese, and molybdenum. Fifty-nine pigments were organic, of which most were azo, quinacridone, or anthraquinone dyes. A literature search revealed that 10 of the 79 pigments were associated with allergic contact dermatitis. CONCLUSION: Permanent makeup primarily uses organic pigments, although some metallic pigments are still used. Physicians should also be aware that some of these pigments-both organic and inorganic-are known causes of allergic contact dermatitis. Of note, patch testing to these ingredients can be negative.

Reprocessable Polymer Networks Containing Sulfur-Based, Percolated Dynamic Covalent Cross-Links and Percolated or Non-Percolated, Static Cross-Links.

One method to improve the properties of covalent adaptable networks (CANs) is to reinforce them with a fraction of permanent cross-links without sacrificing their (re)processability. Here, a simple method to synthesize poly(n-hexyl methacrylate) (PHMA) and poly(n-lauryl methacrylate) (PLMA) networks containing static dialkyl disulfide cross-links (utilizing bis(2-methacryloyl)oxyethyl disulfide, or DSDMA, as a permanent cross-linker) and dynamic dialkylamino sulfur-sulfur cross-links (utilizing BiTEMPS methacrylate as a dissociative dynamic covalent cross-linker) is presented. The robustness and (re)processability of the CANs are demonstrated, including the full recovery of cross-link density after recycling. The authors also investigate the effect of static cross-link content on the stress relaxation responses of the CANs with and without percolated, static cross-links. As PHMA and PLMA have very different activation energies of their respective cooperative segmental mobilities, it is shown that the dissociative CANs without percolated, static cross-links have activation energies of stress relaxation that are dominated by the dissociation of BiTEMPS methacrylate cross-links rather than by the cooperative relaxations of backbone segments, i.e., the alpha relaxation. In CANs with percolated, static cross-links, the segmental relaxation of side chains, i.e., the beta relaxation, is critical in allowing for large-scale stress relaxation and governs their activation energies of stress relaxation.

Predictors for new-onset conduction block in patients with pure native aortic regurgitation after transcatheter aortic valve replacement with a new-generation self-expanding valve (VitaFlow Liberty™): a retrospective cohort study.

BACKGROUND: New-generation self-expanding valves can improve the success rate of transcatheter aortic valve replacement (TAVR) for severe pure native aortic regurgitation (PNAR). However, predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves in patients with PNAR remain to be established. Therefore, this study aimed to identify predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves (VitaFlow Liberty™) in patients with PNAR. METHODS: In this retrospective cohort study, patients were categorized into pacemaker and non-pacemaker groups based on their need for new postoperative permanent pacemaker implantation (PPI). Based on the postoperative presence of either new-onset complete left bundle branch block (cLBBB) or high-grade atrioventricular block (AVB), patients were further classified into conduction disorder and non-conduction disorder groups. Laboratory, echocardiographic, computed tomography, preoperative and postoperative electrocardiography, and procedural and clinical data were collected immediately after TAVR and during hospitalization and compared between the groups. Multivariate logistic regression analysis was performed incorporating the significant variables from the univariate analyses. RESULTS: This study examined 68 consecutive patients with severe PNAR who underwent TAVR. In 20 patients, a permanent pacemaker was fitted postoperatively. Multivariate logistic regression analysis revealed an association between the need for postoperative PPI and preoperative complete right bundle branch block (cRBBB) or first-degree AVB, as well as a non-tubular left ventricular outflow tract (LVOT). In addition, valve implantation depth and angle of aortic root were independent predictors of new-onset cLBBB or high-grade AVB developing post-TAVR. The predictive value of valve implantation depth and angle of aortic root was further supported by receiver operating characteristic curve analysis results. CONCLUSIONS: In patients with PNAR undergoing TAVR using self-expanding valves, preoperative cRBBB or first-degree AVB and a non-tubular LVOT were indicators of a higher likelihood of PPI requirement. Moreover, deeper valve implantation depth and greater angle of aortic root may be independent risk factors for new-onset cLBBB or high-grade AVB post-TAVR. Valve implantation depth and angle of aortic root values may be used to predict the possibility of new cLBBB or high-grade AVB post-TAVR.

Long-term restoration of bowel continuity after rectal cancer resection and the influence of surgical technique: A nationwide cross-sectional study.

AIM: Literature on nationwide long-term permanent stoma rates after rectal cancer resection in the minimally invasive era is scarce. The aim of this population-based study was to provide more insight into the permanent stoma rate with interhospital variability (IHV) depending on surgical technique, with pelvic sepsis, unplanned reinterventions and readmissions as secondary outcomes. METHOD: Patients who underwent open or minimally invasive resection of rectal cancer (lower border below the sigmoid take-off) in 67 Dutch centres in 2016 were included in this cross-sectional cohort study. RESULTS: Among 2530 patients, 1470 underwent a restorative resection (58%), 356 a Hartmann's procedure (14%, IHV 0%-42%) and 704 an abdominoperineal resection (28%, IHV 3%-60%). Median follow-up was 51 months. The overall permanent stoma rate at last follow-up was 50% (IHV 13%-79%) and the unintentional permanent stoma rate, permanent stoma after a restorative procedure or an unplanned Hartmann's procedure, was 11% (IHV 0%-29%). A total of 2165 patients (86%) underwent a minimally invasive resection: 1760 conventional (81%), 170 transanal (8%) and 235 robot-assisted (11%). An anastomosis was created in 59%, 80% and 66%, with corresponding unintentional permanent stoma rates of 12%, 24% and 14% (p = 0.001), respectively. When corrected for age, American Society of Anesthesiologists classification, cTNM, distance to the anorectal junction and neoadjuvant (chemo)radiotherapy, the minimally invasive technique was not associated with an unintended permanent stoma (p = 0.071) after a restorative procedure. CONCLUSION: A remarkable IHV in the permanent stoma rate after rectal cancer resection was found. No beneficial influence of transanal or robot-assisted laparoscopy on the unintentional permanent stoma rate was found, although this might be caused by the surgical learning curve. A reduction in IHV and improving preoperative counselling for decision-making for restorative procedures are required.

Short-term outcomes of heavyweight versus mediumweight synthetic mesh in a retrospective cohort of clean-contaminated and contaminated retromuscular ventral hernia repairs.

BACKGROUND: Mediumweight (40-60 g/m2) polypropylene (MWPP) mesh has been shown to be safe and effective in CDC class II-III retromuscular ventral hernia repairs (RMVHR). However, MWPP has the potential to fracture, and it is possible that heavyweight (> 75 g/m2) polypropylene mesh has similar outcomes in this context. However, there is limited data on HWPP mesh performance in clean-contaminated and contaminated scenarios. We aimed to compare HWPP to MWPP mesh in CDC class II-III wounds during open RMVHR. METHODS: The Abdominal Core Health Quality Collaborative database was retrospectively queried for a cohort of patients who underwent open RMVHR with MWPP or HWPP mesh placed in CDC class II/III wounds from 2012 to 2023. Mesh types were compared using a 3:1 propensity score-matched analysis. Covariates for matching included CDC classification, BMI, diabetes, smoking within 1 year, hernia, and mesh width. Primary outcome of interest included wound complications. Secondary outcomes included reoperations and readmissions at 30 days. RESULTS: A total of 1496 patients received MWPP or HWPP (1378 vs. 118, respectively) in contaminated RMVHR. After propensity score matching, 351 patients remained in the mediumweight and 117 in the heavyweight mesh group. There were no significant differences in surgical site infection (SSI) rates (13.4% vs. 14.5%, p = 0.877), including deep SSIs (0.3% vs. 0%, p = 1), surgical site occurrence rates (17.9% vs. 22.2%, p = 0.377), surgical site occurrence requiring procedural intervention (16% vs. 17.9%, p = 0.719), mesh removal (0.3% vs. 0%, p = 1), reoperations (4.6% vs. 2.6%, p = 0.428), or readmissions (12.3% vs. 9.4%, p = 0.504) at 30 days. CONCLUSION: HWPP mesh was not associated with increased wound morbidity, mesh excisions, reoperations, or readmissions in the early postoperative period compared with MWPP mesh in open RMVHR for CDC II/III cases. Longer follow-up will be necessary to determine if HWPP mesh may be a suitable alternative to MWPP mesh in contaminated scenarios.

Permanent stoma rate and long-term stoma complications in laparoscopic, robot-assisted, and transanal total mesorectal excisions: a retrospective cohort study.

BACKGROUND: The surgical resection of rectal carcinoma is associated with a high risk of permanent stoma rate. Primary anastomosis rate is suggested to be higher in robot-assisted and transanal total mesorectal excision, but permanent stoma rate is unknown. METHODS: Patients undergoing total mesorectal excision for MRI-defined rectal cancer between 2015 and 2017 in 11 centers highly experienced in laparoscopic, robot-assisted or transanal total mesorectal excision were included in this retrospective study. Permanent stoma rate, stoma-related complications, readmissions, and reoperations were registered. A multivariable regression analysis was performed for permanent stoma rate, stoma-related complications, and stoma-related reoperations. RESULTS: In total, 1198 patients were included. Permanent stoma rate after low anterior resection (with anastomosis or with an end colostomy) was 40.1% in patients undergoing laparoscopic surgery, 21.3% in patients undergoing robot-assisted surgery, and 25.6% in patients undergoing transanal surgery (P < 0.001). Permanent stoma rate after low anterior resection with an anastomosis was 17.3%, 11.8%, and 15.1%, respectively. The robot-assisted and transanal techniques were independently associated with a reduction in permanent stoma rate in patients who underwent a low anterior resection (with anastomosis or with an end colostomy) (OR 0.39 [95% CI 0.25, 0.59] and OR 0.35 [95% CI 0.22, 0.55]), while this was not seen in patients who underwent a restorative low anterior resection. 45.4% of the patients who had a stoma experienced stoma-related complications, 4.0% were at least once readmitted, and 8.9% underwent at least one reoperation. CONCLUSIONS: The robot-assisted and transanal techniques are associated with a lower permanent stoma rate in patients who underwent a low anterior resection.