A transcriptionally repressed quiescence program is associated with paused RNA polymerase II and is poised for cell cycle re-entry.

Adult stem cells persist in mammalian tissues by entering a state of reversible quiescence, referred to as G0, which is associated with low levels of transcription. Using cultured myoblasts and muscle stem cells, we report that in G0, global RNA content and synthesis are substantially repressed, correlating with decreased RNA polymerase II (RNAPII) expression and activation. Integrating RNAPII occupancy and transcriptome profiling, we identify repressed networks and a role for promoter-proximal RNAPII pausing in G0. Strikingly, RNAPII shows enhanced pausing in G0 on repressed genes encoding regulators of RNA biogenesis (such as Ncl, Rps24, Ctdp1), and release of pausing is associated with increased expression of these genes in G1. Knockdown of these transcripts in proliferating cells leads to induction of G0 markers, confirming the importance of their repression in establishment of G0. A targeted screen of RNAPII regulators revealed that knockdown of Aff4 (a positive regulator of elongation) unexpectedly enhances expression of G0-stalled genes and hastens S phase; however, the negative elongation factor (NELF) complex, a regulator of pausing, appears to be dispensable. We propose that RNAPII pausing contributes to transcriptional control of a subset of G0-repressed genes to maintain quiescence and impacts the timing of the G0-G1 transition. This article has an associated First Person interview with the first authors of the paper.

Greater TIMP-1 protein levels and neointimal formation represent sex-dependent cellular events limiting aortic vessel expansion in female rats.

Fragmentation/loss of the structural protein elastin represents the precipitating event translating to aortic expansion and subsequent aneurysm formation. The present study tested the hypothesis that greater protein expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) and neointimal growth secondary to a reduction of medial elastin content represent sex-dependent events limiting aortic vessel expansion in females. TIMP-1 protein levels were higher in the ascending aorta of female versus male patients diagnosed with a bicuspid aortic valve (BAV). The latter paradigm was recapitulated in the aorta of adult male and female rats complemented by greater TIMP-2 expression in females. CaCl2 (0.5 M) treatment of the infrarenal aorta of adult male and female rats increased the in situ vessel diameter and expansion was significantly smaller in females despite a comparable reduction of medial elastin content. The preferential appearance of a neointimal region of the CaCl2-treated infrarenal aorta of female rats may explain in part the smaller in situ expansion and neointimal growth correlated positively with the % change of the in situ diameter. Neointimal formation was secondary to a significant increase in the density of medial/neointimal vascular smooth muscle cells (VSMCs) that re-entered the G2-M phase whereas VSMC cell cycle re-entry was attenuated in the CaCl2-treated infrarenal aorta of male rats. Thus, greater TIMP-1 expression in the aorta of female BAV patients may prevent excessive elastin fragmentation and preferential neointimal growth following CaCl2-treatment of the infrarenal aorta of female rats represents a sex-dependent biological event limiting vessel expansion secondary to a significant loss of the structural protein.

Optimal timing of staged percutaneous coronary intervention after subintimal tracking and re-entry: Rationale and design of the subintimal tracking and re-entry with deferred stenting study.

BACKGROUND: Ten to fifteen percent of chronic total occlusion (CTO) percutaneous coronary interventions (PCIs) are unsuccessful in contemporary practice. Subintimal tracking and re-entry (STAR) (one form of "investment procedure") with staged reattempt and stenting may further increase the ultimate success and safety of CTO as a bailout strategy. The optimal timing for staged stenting after STAR is unknown. METHODS AND RESULTS: We designed a six-center, prospective randomized trial with a planned enrollment of 150 patients where STAR is utilized in case of impending failure. The primary aim is to evaluate the optimal timing of the staged PCI after STAR by randomizing the timing to earlier (5-7 weeks) versus later (12-14 weeks) staged PCI. The primary endpoint of the study is the technical success rate of the staged procedure. The secondary endpoints include: (1) the rate of thrombolysis in myocardial infarction 3 flow at the start of staged intervention, (2) rate of partial technical and procedural success of the staged procedure, (3) rate of in-hospital and 12-month major cardiac and cerebrovascular adverse events, and (4) change in patient-reported quality at 30 days, 6 months, and 12 months assessed by Seattle Angina Questionnaire. CONCLUSION: This study will ascertain the optimal timing of staged stenting after bail-out STAR approach in contemporary CTO PCI (ClinicalTrials.gov NCT05089864).

Blood donation screening for hepatitis B virus core antibodies: The importance of confirmatory testing and initial implication for rare blood donor groups.

BACKGROUND AND OBJECTIVES: Exclusion of blood donors with hepatitis B virus (HBV) core antibodies (anti-HBc) prevents transfusion-transmitted HBV infection but can lead to significant donor loss. As isolated anti-HBc positivity does not always indicate true past HBV infection, we have investigated the effectiveness of confirmatory anti-HBc testing and the representation of rare blood groups in anti-HBc-positive donors. MATERIALS AND METHODS: Three hundred ninety-seven HBV surface antigen-negative and anti-HBc initially reactive blood donor samples were tested by five different anti-HBc assays. RESULTS: Eighty percentage of samples reactive in Architect anti-HBc assay were positive by the Murex assay and anti-HBc neutralization. Eleven out of 397 samples showed discordant results in supplementary testing from the Murex confirmatory test result, and five remained undetermined following extensive serological testing. Thirty-eight percentage of anti-HBc-positive donors identified as minority ethnic groups compared with 11% representation in anti-HBc-negative donors (p < 0.0001); the frequency of the Ro blood group in anti-HBc-positive donors was 18 times higher in non-white ethnic groups. CONCLUSION: Using two anti-HBc assays effectively enabled the identification of HBV-exposed and potentially infectious donors, their deferral and potential clinical follow-up. However, the exclusion of confirmed anti-HBc-positive donors will still impact the supply of rare blood such as Ro.

Retrospective Case Control Matched Comparison of the Antegrade Versus Retrograde Strategy After Antegrade Recanalisation Failure in Complex de novo Femoropopliteal Occlusive Lesions.

OBJECTIVE: To investigate dissection severity, need for bailout stenting and limb outcomes in patients undergoing antegrade vs. retrograde revascularisation. METHODS: Consecutive patients who underwent either antegrade or retrograde revascularisation after failed antegrade recanalisation of long femoropopliteal chronic total occlusion (CTO) due to symptomatic peripheral artery disease between January 2017 and June 2022 were studied. Retrospective case control matching was used to adjust for lesion length and calcification using the peripheral artery calcification scoring system (PACSS). Procedural outcomes included severity of dissection (Type A to F dissections, numerically graded on a scale from 0 - 6 with increasing severity) after angioplasty and number and location of stents needed to be implanted during the index procedure. Additionally, clinically driven target lesion revascularisation (CD-TLR) and major (above ankle) amputation rates were assessed during follow up. RESULTS: A total of 180 patients were analysed who underwent antegrade (n = 90) or retrograde after failed antegrade (n = 90) recanalisation. The median patient age was 76.0 (interquartile range [IQR] 67.0, 82.0) years and 76 (42.2%) were female. Moreover, 78 patients (43.3%) had intermittent claudication, whereas 102 (56.7%) had chronic limb threatening ischaemia (CLTI). The mean lesion length was 30.0 (IQR 24.0, 36.0) cm with moderate to severe (3.0 [IQR 2.0, 4.0]) lesion calcification. Dissection severity after angioplasty was higher in the antegrade than retrograde after failed antegrade recanalisation group (4.0 [IQR 3.0, 4.0] vs. 3.0 [IQR 2.0, 4.0]; p < .001). Additionally, the number of stents in all segments and the rate of bailout stenting in popliteal segments was significantly higher with the antegrade strategy (2.0 [IQR 1.0, 3.0] vs. 1.0 [IQR 0, 2.0], p < .010; and 37% vs. 14%, p < .001). During a median follow up of 1.48 (IQR 0.63, 3.09) years, CD-TLR rates (p = .90) and amputation rates in patients with CLTI (p = .15) were not statistically significant. CONCLUSION: In complex femoropopliteal CTOs, retrograde after failed antegrade recanalisation, is safe for endovascular revascularisation, which in experienced hands may result in less severe dissections and lower rates of stent placement. However, considering the relatively short follow up, CD-TLR and amputation rates were not statistically different between the two approaches. [German Clinical Trials Register: DRKS00015277.].

Dislodgeable Foliar Residue Measurements and Assessment of Dermal Exposure to Captan for Workers in Apple Orchards.

Captan dislodgeable foliar residues (DFRs) were determined by following the applications of this fungicide in an apple orchard. The study comprised an investigation of the variability of captan DFR values and 14 days of DFR monitoring to assess kinetic modeling. A method combining solid-phase microextraction (SPME) gas chromatography and high-resolution mass spectrometry (GC-QTOF-MS) was developed for the quantification of captan residues from DFR aqueous extracts. The results evidenced that (1) sampling parameters such as the position of the tree in a row and the height of foliar significantly influenced captan DFR levels (247-1450 ng·cm-2), highlighting the need to implement a comprehensive sampling strategy; (2) the DFR captan dissipation kinetic model best matched with a biphasic one, with half-lives of DFRcaptan of 3.4 and 12.8 days, respectively, for the initial rapid phase 1 decline (day 0-5) and the slower phase 2 decline phase (day 6-14). Furthermore, through DFR measurements, the potential dermal exposure (PDE) of workers was assessed using transfer coefficients (TCs) from the literature. Compared to the acceptable operator exposure levels (AOELs), the results showed that the re-entry interval for captan may not sufficiently protect workers whose arms, hands, and legs are not covered.

Cinnamaldehyde protects SH-SY5Y cells against advanced glycation end-products induced ectopic cell cycle re-entry.

Accumulation of advanced glycation end-products (AGEs) in the brain contributes significantly to cognitive impairment in patients with diabetes by disrupting the post-mitotic state of neuronal cells, thereby triggering ectopic cell cycle re-entry (CCR) and subsequent neuronal apoptosis. Cinnamaldehyde (CINA), a potential mitigator of cognitive impairment due to its blood glucose-lowering properties, warrants exploration for its role in counteracting diabetes-related neurological damage. In this study, we examined the neuroprotective effect of CINA on AGE-damaged SH-SY5Y human neuroblastoma cells differentiated in vitro. We investigated the impact of CINA on AGE-induced neuronal CCR and apoptosis, finding that it substantially suppressed aberrant DNA replication, precluded cells from entering the mitotic preparatory phase, and diminished apoptosis. Additionally, CINA inhibited the expression of eIF4E without altering S6K1 phosphorylation. These findings indicate that CINA safeguards neuronal cells from AGE-related damage by preventing abnormal CCR, preserving the post-mitotic state of neuronal cells, and reducing AGE-induced apoptosis, potentially through the inhibition of eIF4E-controlled cell proliferation. Our results highlight the prospective utility of CINA in managing diabetic neuropathy.

Social support during re-entry period and long-term quality of life in breast cancer survivors: a 10-year longitudinal cohort study.

PURPOSE: This study evaluated the association between social support during the re-entry period and long-term health-related quality of life (HRQoL) in breast cancer survivors using a longitudinal cohort study. METHODS: This is a prospective cohort study with 275 breast cancer survivors who reported HRQoL at 5 and 10 years after diagnosis. Social support for the re-entry period was measured 3 years after diagnosis using the Medical Outcome Study Social Support Survey (MOS-SSS). HRQoL was evaluated using the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and Breast Cancer-Specific Module (BR-23). Multivariable linear regression analysis was performed to evaluate HRQoL at 5 and 10 years after diagnosis by level of social support during the re-entry period. RESULTS: The mean (SD) of social support during re-entry period was 68.5. The low social support (LSS, score < 55) group during the re-entry period had a significantly lower HRQoL (mean difference = - 12.93) compared to moderate or high social support (MHSS, score ≥ 55) group. 5 and 10 years after diagnosis, the LSS group continued to demonstrate lower HRQoL (5 years: - 7.17; 10 years: - 7.85) compared to the MHSS group. The LSS group were more likely to have lower role and social function scores, and higher fatigue, pain, and financial problems compared to the MHSS group at 10 years after diagnosis. CONCLUSIONS: Breast cancer survivors who received lower social support during the re-entry period were more likely to experience poorer HRQoL in the long term than those who did not.

Challenges, experiences, and potential supports for East and Southeast Asian mothers in the workforce: a systematic review.

OBJECTIVE: To examine the challenges faced by Asian working mothers with a focus on re-entry to the workplace. In addition, we highlight potential supports that retain women in the workforce. DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) recommendations and registered with PROSPERO database (CRD42022341130). METHODS: Three independent reviewers were involved in the study selection to screen the search results sequentially by title, abstract, and full text using predefined inclusion and exclusion criteria. The methodological quality of each article was assessed via the Critical Appraisal Skills Programme (CASP) tool. RESULTS: We analysed a total of 36 studies conducted across different regions: 30 from the East and 6 from Southeast Asia. Among these studies, 20 were quantitative in nature, 15 were qualitative, and one intervention. The 36 studies cover five themes: 1) policies, 2) external support sources, 3) external pressure, 4) breastfeeding and 5) health status. Within each theme the same factor can have a positive or negative impact on the mother depending on her having a pro-career or pro-family mindset. Companies can take various initiatives to support working mothers, such as providing facilities for expressing breast milk at the workplace, educating staff to promote breastfeeding and accommodate childcare needs, and extending maternity leaves. However, there is a lack of literature that directly addresses the barriers and concrete support available to working mothers in Asia, beyond the scope of breastfeeding. CONCLUSIONS: Our findings underscore several obstacles that can impede a woman's seamless return to work. Pro-family and pro-career mothers have differing needs that cannot be addressed at the same time. There is a lack of comprehensive understanding regarding effective strategies or interventions that can support a positive reintegration into the workforce.

Successful return to work in anaesthesia after maternity leave: a qualitative study.

Returning to work after maternity leave poses significant challenges, with potential long-term implications including decreased engagement or attrition of clinicians. Many quantitative studies have identified challenges and supports for women during pregnancy, maternity leave and re-entry to clinical practice. This qualitative study explored the experiences of anaesthetists returning to clinical work after maternity leave, to identify influential factors with the aim of providing a framework to assist planning re-entry. We conducted semi-structured interviews with 15 anaesthetists. Attendees of a re-entry programme were invited to participate, with purposive sampling and snowball recruitment to provide diversity of location and training stage, until data saturation was reached at 13 interviews. Five themes were identified: leave duration; planning re-entry; workplace culture; career impact and emotional impact. Leave duration was influenced by concerns about deskilling, but shorter periods of leave had logistical challenges, including fatigue. Most participants started planning to return to work with few or no formal processes in the workplace. Workplace culture, including support for breastfeeding, was identified as valuable, but variable. Participants also experienced negative attitudes on re-entry, including difficulty accessing permanent work, with potential career impacts. Many participants identified changes to professional and personal identity influencing the experience with emotional sequelae. This research describes factors which may be considered to assist clinicians returning to work after maternity leave and identifies challenges, including negative attitudes, which may pose significant barriers to women practising in anaesthesia and may contribute to lack of female leadership in some workplaces.

Proposals for new transfer coefficient (TC) values for worker re-entry activities in grape vineyards.

New transfer coefficient (TC) values were derived for vineyard workers handling treated grapevines during harvesting and crop maintenance activities. Re-entry exposure and dislodgeable foliar residue (DFR) studies were performed in Europe, covering hand harvesting, pruning/training, pruning/tying and pruning/shoot lifting. Foliar applications of fungicides (iprovalicarb, dimethomorph, dithianon, pyrimethanil and fenbuconazole) were made and 73 workers at 16 sites were monitored over one working day. Exposure was measured on inner and outer dosimeters, face/neck wipes and hand washes. In concurrent DFR studies, leaf punches were taken at each site during the time of worker re-entry. Potential exposure values correlated well with DFR values. TC values were derived for various re-entry activities for potential and actual exposure, with and without gloves. The harvesting task resulted in lower TC values than the other crop maintenance tasks. Additional TC values reflecting the use of protective gloves can be derived from the results. The TC values are much lower than current European Food Safety Authority (EFSA) default values. This project addresses a data gap identified by EFSA for specific EU TC values to permit more realistic and reliable re-entry worker exposure estimates for grapes.

Six-month post-release outcomes for inmates with traumatic brain injury in supported community programming.

OBJECTIVE: The goal of this study is to examine the effectiveness of case management services for a population of justice-involved individuals with TBI history. METHODS: Two thousand three hundred and eighty-nine records from statewide behavioral health and brain injury program databases were used in two studies. RESULTS: Participants with a reported TBI history were more likely to have experienced trauma and to have a behavioral health diagnosis relative to incarcerated persons without TBI. Six months after release, 56.8% of participants with a history of TBI were still receiving community treatment, 27.8% were not in treatment, and 3.4% had completed treatment. There was a high attrition rate; 70% of people referred for case management failed to maintain contact. CONCLUSIONS: For those that did receive services, these data suggest that it prevented an escalation of psychosocial needs. There were no differences in community participation as measured by the Mayo Portland Adaptability Index's Participation Index (M2PI) scores (t24 = .497, p = 0.624) at intake and after 6 months of case management. This study confirms that case management confers a benefit to persons with TBI who are released from the criminal justice system. Further, recidivism rates for this vulnerable group were no different from the larger population of returning citizens.

The role of ethnicity in the admission process of male juvenile released offenders: Examining risk and readiness to change in the Israeli Shushan centers.

INTRODUCTION: Disparities in evaluating readiness to change and recidivism risk across diverse cultural groups can profoundly affect rehabilitation program efficacy. This study examines readiness to change and recidivism risk disparities between Israeli-Arabs and Israeli-Jews entering a re-entry program by the Prisoner Rehabilitation Authority postrelease. METHOD: The University of Rhode Island Change Assessment Scale questionnaire gauged readiness to change, whereas the Ohio Youth Assessment System-Residential tool assessed recidivism risk. The sample included 151 participants: 98 Israeli-Arabs and 53 Israeli-Jews. Mean differences in change readiness and recidivism risk were statistically assessed through t tests. RESULTS: Significant differences emerged in change readiness levels between Israeli-Arabs and Jews upon rehabilitation program entry, with Israeli-Jews exhibiting higher readiness. Additionally, a noteworthy divergence in recidivism risk was noted, indicating elevated average risk for Israeli-Jews. CONCLUSIONS: Findings underscore the vital need for cultural sensitivity during admission. Bias potential in assessing risk for Arab participants emphasizes the necessity of a comprehensive culturally sensitive approach. While focusing on admission, the Risk-Need-Responsivity model application could enhance risk evaluation and guide culturally tailored treatments.

Expanding Treatment, Recovery, and Reentry Services for Female Offenders: Improving Outcomes through Client-Centered Interventions.

This study investigated the impact of a specialized program aimed at improving substance use disorder and trauma treatment, recovery, and reentry services for adult female offenders. Trained recovery coaches delivered pretreatment interventions such as prescreening, motivational interviewing, and support-building to facilitate treatment entry and improve outcomes. Of 113 participants, 40% identified as racial/ethnic minorities, and 72% fell within the 25-45 age range. A notable 44.5% reduction in self-reported psychiatric symptoms was observed, alongside significant improvements in abstinence and trauma symptoms. Recovery capital and psychosocial functioning showed marked improvement including significant changes in employment status and housing stability and a decrease in criminal justice involvement. The results suggest that targeted, client-centered approaches can effectively improve recovery and psychosocial functioning among female offenders while reducing re-incarceration rates. These findings underscore the importance of addressing the unique needs of this population in both pre-and post-release settings to ensure equitable access to reentry services.

Self-stigma of incarceration and its impact on health and community integration.

BACKGROUND: Individuals returning to the wider community from incarceration face many re-entry barriers, including stigmatising beliefs regarding past criminal record, that have impact on health and re-entry. Understanding the development and impact of self-stigma on health can inform re-entry and rehabilitation services. AIMS: The two aims of this study were first, to evaluate a previously established model of self-stigma applied to individuals who have experienced incarceration and, secondly, to study the impact of self-stigma on physical and mental health as well as community integration on re-entry. METHODS: This is a cross-sectional study of 129 formerly incarcerated adults recruited using an online platform and asked to complete online rating scales about self-stigmatisation, health and sense of community integration. Repeated-measures analysis of variance, correlation analysis, and path analyses were used to evaluate the model. RESULTS: There was support for the four distinct stages of self-stigmatisation apparent in mental health research. There was a relationship between self-stigma harm and sense of community integration, mediated by mental but not physical health status scores. CONCLUSION: Our findings add to work on self-stigmatisation in the field of mental health by showing that the concept appears relevant and appears in similar staging among formerly incarcerated individuals and that self-stigmatisation is likely to be important for their community reintegration. Our sample was not typical of the wider prison population for race and gender distribution, in particular having fewer than expected those minority groups likely to be especially vulnerable to stigmatisation by others. Our findings nevertheless suggest that further, preferably, longitudinal research on self-stigma to enable better understanding of pathways could substantially help treatment and rehabilitation of individuals after release from a correctional facility.

Examining a Triple Threat: The Intersection of Mental Health, Substance Use, and Re-entry of a Sample of Justice-Involved Persons.

Having a mental health (MH) or substance use (SU) issue can make the transition from prison to the community a challenging process. Despite this, few studies have quantified how justice-involved individuals with mental health issues only, substance use only, those with both struggles, and those with neither are uniquely affected. Using a sample of re-entering men who were released from twelve state prisons in the United States, we assessed the effects of having MH and SU issues on their drug use during re-entry. Furthermore, we examined their differing coping reactions to housing insecurity, joblessness, and family tension after release. The results demonstrated that respondents' risk of SU during re-entry was associated with MH and SU issues measured at release. Those with co-occurring MH and SU challenges were at the highest risk of SU during re-entry. Furthermore, challenging life situations during re-entry exerted an amplified effect on SU for respondents with both anxiety and SU issues. The findings suggest that post-incarcerated individuals with co-occurring MH and SU issues have the highest risk of SU, and their reaction to re-entry barriers is distinct from their peers. Quality services to address co-occurring MH and SU may be needed to facilitate a smooth transition from prison to the community.

Distinct protein kinase C isoforms drive the cell cycle re-entry of two separate populations of neonatal rat ventricular cardiomyocytes.

The present study tested the hypothesis that protein kinase C-α (PKC-α) recruitment in the presence of the p38α/ß MAPK inhibitor SB203580 facilitated the appearance and cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes (NNVMs) and induced a transcript profile delineating a proliferative phenotype. Phorbol 12,13-dibutyrate (PDBu) treatment did not induce de novo nestin expression or increase the cell cycle re-entry of 1-day-old NNVMs but significantly increased runt-related transcription factor 1 (Runx1) and p16 cell cycle inhibitor (CDKN2a) mRNA levels and downregulated epithelial cell transforming 2 (ECT2) mRNA expression. SB203580 administration to PDBu-treated NNVMs induced de novo nestin expression, preferentially increased the density (normalized to 500 NNVMs) of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu, 1.4 ± 3 vs. PDBu/SB203580, 128 ± 34; n = 5 independent litters), significantly inhibited CDKN2a and Runx1 mRNA upregulation and reversed ECT2 mRNA downregulation. PDBu treatment of NNVMs reduced PKC-α, protein kinase-δ (PKC-δ) and protein kinase-ε (PKC-ε) protein levels and GF109203X (conventional PKC isoform inhibitor) selectively attenuated PKC-α protein downregulation. GF109203X administration to PDBu/SB203580-treated NNVMs significantly reduced the density of nestin(+)-NNVMs that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 40 ± 46; n = 5). Moreover, GF109203X/PDBu/SB203580 treatment unmasked the predominant appearance of a separate NNVM population that incorporated 5-bromo-2'-deoxyuridine (PDBu/SB203580/GF109203X, 192 ± 42; n = 5) delineated by the absence of de novo nestin expression. Sotrastaurin (conventional/novel PKC isoform inhibitor) administration to PDBu/SB203580-treated NNVMs significantly attenuated the density of nestin(+)-NNVMs (PDBu/SB203580/sotrastaurin, 8 ± 10; n = 4) and nestin(-)-NNVMs (PDBu/SB203580/sotrastaurin, 64 ± 30; n = 4) that incorporated 5-bromo-2'-deoxyuridine. These data reveal that the neonatal rat heart contains at least two separate populations of NNVMs that re-enter the cell cycle and the preferential appearance of nestin(+)- or nestin(-)-NNVMs is driven by distinct PKC isoforms in the presence of SB203580.NEW & NOTEWORTHY The appearance of nestin(+)-neonatal rat ventricular cardiomyocytes that re-entered the cell cycle following phorbol ester stimulation in the presence of p38α/ß MAPK inhibitor SB203580 was associated with the inhibition of Runx1 and CDKN2a mRNA upregulation. PKC-α selectively induced the cell cycle re-entry of nestin(+)-neonatal rat ventricular cardiomyocytes. Pharmacological inhibition of PKC-α with concomitant p38α/ß MAPK suppression unmasked the cell cycle re-entry of a second population of neonatal rat ventricular cardiomyocytes in the absence of nestin expression.

STAR procedure becomes SAFER: First-in-man case series of a new antegrade dissection re-entry technique.

INTRODUCTION: Antegrade dissection and re-entry (ADR) is an integral part of the hybrid algorithm, which has allowed for improved outcomes in chronic total occlusion (CTO) coronary intervention (PCI). METHODS: A new ADR method, Subintimal Antegrade FEnestration and Re-entry (SAFER), is described. The results of a first-in-man series are presented. RESULTS: SAFER was performed on seven consecutive patients with angiographic and clinical success in all patients. CONCLUSIONS: This first-in-man study has shown that the SAFER technique is feasible and effective with the possibility of improving the antegrade PCI CTO success rate.

Wire-based antegrade dissection re-entry technique for coronary chronic total occlusions percutaneous revascularization: Experience from the ERCTO Registry.

BACKGROUND: The recent development and widespread adoption of antegrade dissection re-entry (ADR) techniques have been underlined as one of the antegrade strategies in all worldwide CTO consensus documents. However, historical wire-based ADR experience has suffered from disappointing long-term outcomes. AIMS: Compare technical success, procedural success, and long-term outcome of patients who underwent wire-based ADR technique versus antegrade wiring (AW). METHODS: One thousand seven hundred and ten patients, from the prospective European Registry of Chronic Total Occlusions (ERCTO), underwent 1806 CTO procedures between January 2018 and December 2021, at 13 high-volume ADR centers. Among all 1806 lesions attempted by the antegrade approach, 72% were approached with AW techniques and 28% with wire-based ADR techniques. RESULTS: Technical and procedural success rates were lower in wire-based ADR than in AW (90.3% vs. 96.4%, p < 0.001; 87.7% vs. 95.4%, p < 0.001, respectively); however, wire-based ADR was used successfully more often in complex lesions as compared to AW (p = 0.017). Wire-based ADR was used in most cases (85%) after failure of AW or retrograde procedures. At a mean clinical follow-up of 21 ± 15 months, major adverse cardiac and cerebrovascular events (MACCEs) did not differ between AW and wire-based ADR (12% vs. 15.1%, p = 0.106); both AW and wire-based ADR procedures were associated with significant symptom improvements. CONCLUSIONS: As compared to AW, wire-based ADR is a reliable and effective strategy successfully used in more complex lesions and often after the failure of other techniques. At long-term follow-up, patient's MACCEs and symptoms improvement were similar in both antegrade techniques.

In Situ Fenestrated Thoracic Endovascular Repair Using the Upstream Peripheral Go BackTM Re-Entry Catheter.

PURPOSE: The aim is to present a case of in situ fenestrated thoracic endovascular repair, using a re-entry peripheral catheter, needing urgent repair due to recurrent episodes of hemoptysis because of an aorto-bronchial fistula after previous thoracic endovascular aortic repair (TEVAR). TECHNIQUE: A 74-year-old male with a previous TEVAR presented with hemoptysis, fever, and cachexia. An aorto-bronchial fistula and type Ia endoleak were depicted on computed tomography angiography (CTA). Due to the patient's frail general condition, a proximal TEVAR extension was planned, prior to thoracotomy for debridement, and long-term antibiotics. An in situ fenestrated TEVAR was performed to provide proximal sealing and revascularize the left common carotid and subclavian arteries. For fenestration creation, an Upstream Peripheral Go Back catheter (Bentley, Hechingen, Germany) was used. The Go Back catheter has been approved as a re-entry tool for complex peripheral arterial revascularization. In this case, both fenestrations were successfully created. Proximal seal and target vessel patency were confirmed on CTA. Thoracotomy confirmed aortic exclusion. A wedge lobectomy was performed in combination with pediculated omentectomy to exclude the exposed endograft. CONCLUSION: In urgent cases, where custom-made thoracic devices are unavailable, in situ fenestrations with the Go Back catheter are an alternative to laser fenestrations. CLINICAL IMPACT: Fenestrations are often required in acute TEVAR to achieve a proximal seal in the arch. In situ fenestrations with the Go Back catheter are an alternative to laser fenestrations and PMEGs in this setting.