Search

Summary:. For decades, oncoplastic techniques have been an emerging, yet underutilized approach to breast cancer surgery. Recent developments in breast oncology support the potential for the omission of radiation therapy in a subset of patients eligible for breast-conserving surgery, which makes immediate reconstruction available to a much larger demographic. Although existing oncoplastic methods have offered durable and cosmetically acceptable results in select cases, there remains significant room for improvement. This publication presents a novel option in oncoplastic reconstruction named Breast–Areola Reduction/Reconstruction (BARR) that utilizes the tenets of a superomedial pedicle breast reduction and a Wise-pattern closure to address asymmetry and deformity in treatment of central breast cancers. The BARR technique features principles that are foundational to plastic surgery training, which should augment the acquisition and delivery of oncoplastic surgery in the era of progress to come.

The integration of semi-transparent photovoltaics into the roof of greenhouses is an emerging technique used in recent years, due to the simultaneous energy and food production from the same piece of land. Although shading in many cases is a solution to maintain the desired microclimate, in the case of photovoltaic installations, the permanent shading of the crop is a challenge, due to the importance of light to the growth, morphogenesis, and other critical physiological processes. In this study, the effect of shade from semi-transparent photovoltaics on a strawberry crop (Fragaria x ananassa Duch.) was examined, in terms of growth and quality (phenolic and flavonoid concentration of fruits). According to the results, in non-shaded plants, there was a trend of larger plants, but without a significant change in leaf number, while the total number of flowers was slightly higher at the end of the cultivation period. Moreover, it was found that the percentage change between the number of ripe fruits was smaller than that of the corresponding change in fruit weight, implying the increased size of the fruits in non-shaded plants. Finally, regarding the antioxidant capacity, it was clearly demonstrated that shading increased the total phenolic content, as well as the free-radical-scavenging activity of the harvested fruits. Although the shading from the semi-transparent photovoltaics did not assist the production of large fruits, it did not affect their number and increased some of their quality characteristics. In addition, the advantageous impact of the semi-transparent photovoltaics in the energy part must not be neglected.

Background: Prospective single and multicenter studies have shown improved outcomes of patients who underwent carotid artery stenting with the novel CGuard dual-layer mesh stent at 1 year. Objectives: The aim of this study is to conduct a systematic review and meta-analysis of all published studies to assess 1-year efficacy and outcomes of CGuard in patients with carotid stenting. Methods: A systematic search was performed. All studies enrolling at least 20 patients were included in our analysis. The primary endpoints were death (all-cause, cardiovascular and ipsilateral stroke-related death) and stroke rate at 1 year. The secondary endpoint was in-stent restenosis at 1 year. Results: The final analysis included 1709 patients. The one-year all-cause mortality rate was 2.97% (39/1699, 95% CI: 1.26–6.86%, I2 = 67%, t2 = 0.3442, p < 0.01), cardiovascular-related death was 0.92% (10/1616, 95% CI: 0.35–2.39%, I2 = 34%, t2 = 0.2302, p = 0.18), and ipsilateral stroke-related death was 0.3% (1/1649, 95% CI: 0.1–0.87%, I2 = 0%, t2 = 0, p = 0.69). The one-year ipsilateral stroke rate was 1.21% (16/1649, 95% CI: 0.58–2.5%, I2 = 28%, t2 = 0.1433, p = 0.23), transient ischemic attacks (TIAs) rate was 1.78% (19/1149, 95% CI: 1.11–2.84%, I2 = 0%, t2 = 0, p = 0.69), and total composite 1-year stroke/TIA rate was 2.97% (32/1149, 95% CI: 1.84–4.77%, I2 = 0%, t2 = 0, p = 0.41). The in-stent restenosis rate at 1 year was 1.06% (13/1653, 95% CI: 0.48–2.34%, I2 = 28%, t2 = 0.2308, p = 0.22). Conclusions: This meta-analysis shows that CAS with CGuard is safe with minimal neurological adverse events and in-stent restenosis rate at 1 year.

Interaction of the outer membrane protein (OMP) chaperone SurA and the OMP folding catalyst BAM results in changes in the conformational ensembles of both species, suggesting a mechanism for delivery of OMPs to BAM in Gram-negative bacteria.

Objectives Kenya has long and porous borders with its neighbouring countries. These regions, predominantly inhabited by highly mobile rural communities with strong cross-border cultural ties, present major challenges in managing movement of people and COVID-19 preventive measures. Our study sought to assess knowledge of COVID-19 prevention behaviours, how these varied by socioeconomic (SEC) factors and the challenges of engagement and implementation, in two border counties of Kenya.Methods We conducted a mixed methods study using a household e-survey (Busia, N=294; Mandera, N=288; 57% females, 43% males), and qualitative telephone interviews (N=73: Busia 55; Mandera 18) with policy actors, healthcare workers, truckers and traders, and community members. Interviews were transcribed, English translated and analysed using the framework method. Associations between SEC (wealth quintiles, educational level) and knowledge of COVID-19 preventive behaviours were explored using Poisson regression.Results Participants were mostly educated to primary school level (54.4% Busia, 61.6% Mandera). Knowledge of COVID-19 prevention varied by behaviour: hand washing-86.5%, use of hand sanitiser-74.8%, wearing a face mask-63.1%, covering the mouth when sneezing or coughing-56.3% and social distancing-40.1%. Differences in knowledge by area, educational level and the wealth index were marked, greatest for Mandera, the less educated and the poor. Interviews with stakeholders revealed challenges in health messaging, psychosocial and socioeconomic factors, lack of preparedness for truck border crossings, language barrier, denial and livelihood insecurity as key challenges to engagement with and implementation of COVID-19 prevention behaviours in the border regions.Conclusion The influence of SEC disparities and border dynamics on knowledge and engagement with COVID-19 prevention behaviours calls for contextually appropriate risk communication strategies that are cognisant of community needs and local patterns of information flow. Coordinating response measures across border points is crucial in winning communities’ trust and maintaining essential economic and social activities.

Background Youth adversity (e.g., abuse and bullying victimisation) is robust risk factor for later mental health problems (e.g., depression and anxiety). Research shows the prevalence of youth adversity and rates of mental health problems vary by individual characteristics, identity or social groups (e.g., gender and ethnicity). However, little is known about whether the impact of youth adversity on mental health problems differ across the intersections of these characteristics (e.g., white females). This paper reports on a component of the ATTUNE research programme (work package 2) which aims to investigate the impact and mechanisms of youth adversity on depressive and anxiety symptoms in young people by intersectionality profiles. Methods The data are from 4 UK adolescent cohorts: HeadStart Cornwall, Oxwell, REACH, and DASH. These cohorts were assembled for adolescents living in distinct geographical locations representing coastal, suburban and urban places in the UK. Youth adversity was assessed using a series of self-report questionnaires and official records. Validated self-report instruments measured depressive and anxiety symptoms. A range of different variables were classified as possible social and cognitive mechanisms. Results and analysis Structural equation modelling (e.g., multiple group models, latent growth models) and multilevel modelling will be used, with adaptation of methods to suit the specific available data, in accord with statistical and epidemiological conventions. Discussion The results from this research programme will broaden our understanding of the association between youth adversity and mental health, including new information about intersectionality and related mechanisms in young people in the UK. The findings will inform future research, clinical guidance, and policy to protect and promote the mental health of those most vulnerable to the negative consequences of youth adversity.

Longitudinal evidence on the association between air pollution and blood pressure (BP) in adolescence is scarce. We explored this association in an ethnically diverse cohort of schoolchildren. Sex-stratified, linear random-effects modelling was used to examine how modelled residential exposure to annual average nitrogen dioxide (NO2), particulate matter (PM2.5, PM10) and ozone (O3), measures in μg/m3, associated with blood pressure. Estimates were based on 3,284 adolescents; 80% from ethnic minority groups, recruited from 51 schools, and followed up from 11-13 to 14-16 years old. Ethnic minorities were exposed to higher modelled annual average concentrations of pollution at residential postcode level than their White UK peers. A two-pollutant model (NO2 & PM2.5), adjusted for ethnicity, age, anthropometry, and pubertal status, highlighted associations with systolic, but not diastolic BP. A μg/m3 increase in NO2 was associated with a 0.30 mmHg (95% CI 0.18 to 0.40) decrease in systolic BP for girls and 0.19 mmHg (95% CI 0.07 to 0.31) decrease in systolic BP for boys. In contrast, a 1 μg/m3 increase in PM2.5 was associated with 1.34 mmHg (95% CI 0.85 to 1.82) increase in systolic BP for girls and 0.57 mmHg (95% CI 0.04 to 1.03) increase in systolic BP for boys. Associations did not vary by ethnicity, body size or socio-economic advantage. Associations were robust to adjustments for noise levels and lung function at 11-13 years. In summary, higher ambient levels of NO2 were associated with lower and PM2.5 with higher systolic BP across adolescence, with stronger associations for girls.

Background:. The postoperative prophylactic use of aspirin is a common practice among plastic surgeons after free tissue transfer. The use of baby aspirin (81 mg) has become more popular due to previously published literature in other fields. We hypothesized that a full dose daily aspirin is nonsuperior to a baby dose daily aspirin in preventing arterial thrombosis in free tissue transfer. Methods:. All patients undergoing free tissue transfer of the extremities from 2008 to 2020 were retrospectively reviewed. They were divided into two groups based on the postoperative dose of aspirin administered (full versus baby dose). The decision to administer full or baby dose was based on the surgeon’s preference. Primary outcome was revision of the arterial anastomosis. Secondary outcomes included flap complications. Results:. A total of 183 patients were identified. Out of those, 78 patients received full dose aspirin postoperatively, whereas 105 received a baby dose of aspirin. Patients who received baby aspirin did not have a higher incidence of returning to the operating room for revision of their arterial anastomosis [7.6% versus 7.7%; adjusted odds ratio, 0.93 (95% confidence interval, 0.28‐3.11); adjusted P, 0.906]. No differences were found between the two groups in complete and partial flap loss, wound dehiscence, or infection. None of the patients experienced any aspirin-related gastrointestinal complications. Conclusions:. In patients undergoing free tissue transfer, thrombosis of the arterial anastomosis is rare. Administration of a full dose of aspirin postoperatively was not superior to a baby dose of aspirin in preventing arterial-related complications.

Chemoresistance in colorectal cancer initiating cells (CICs) involves the sustained activation of multiple drug resistance (MDR) and WNT/β-catenin signaling pathways, as well as of alternatively spliced-isoforms of CD44 containing variable exon-6 (CD44v6). In spite of its importance, mechanisms underlying the sustained activity of WNT/β-catenin signaling have remained elusive. The presence of binding elements of the β-catenin-interacting transcription factor TCF4 in the MDR1 and CD44 promoters suggests that crosstalk between WNT/β-catenin/TCF4-activation and the expression of the CD44v6 isoform mediated by FOLFOX, a first-line chemotherapeutic agent for colorectal cancer, could be a fundamental mechanism of FOLFOX resistance. Our results identify that FOLFOX treatment induced WNT3A secretion, which stimulated a positive feedback loop coupling β‐catenin signaling and CD44v6 splicing. In conjunction with FOLFOX induced WNT3A signal, specific CD44v6 variants produced by alternative splicing subsequently enhance the late wave of WNT/β-catenin activation to facilitate cell cycle progression. Moreover, we revealed that FOLFOX-mediated sustained WNT signal requires the formation of a CD44v6-LRP6-signalosome in caveolin microdomains, which leads to increased FOLFOX efflux. FOLFOX-resistance in colorectal CICs occurs in the absence of tumor-suppressor disabled-2 (DAB2), an inhibitor of WNT/β-catenin signaling. Conversely, in sensitive cells, DAB2 inhibition of WNT-signaling requires interaction with a clathrin containing CD44v6-LRP6-signalosome. Furthermore, full-length CD44v6, once internalized through the caveolin-signalosome, is translocated to the nucleus where in complex with TCF4, it binds to β-catenin/TCF4-regulated MDR1, or to CD44 promoters, which leads to FOLFOX-resistance and CD44v6 transcription through transcriptional-reprogramming. These findings provide evidence that targeting CD44v6-mediated LRP6/β-catenin-signaling and drug efflux may represent a novel approach to overcome FOLFOX resistance and inhibit tumor progression in colorectal CICs. Thus, sustained drug resistance in colorectal CICs is mediated by overexpression of CD44v6, which is both a functional biomarker and a therapeutic target in colorectal cancer.

BackgroundClinical outcomes using new generation drug-eluting stents designed specifically for infrapopliteal disease are not widely available, especially in comparison to paclitaxel-based therapies. This series reports 1-year outcomes in patients with diabetes and chronic limb threatening ischaemia (CLTI) undergoing angioplasty, with a sirolimus-eluting tibial stent (Cre8, Alvimedica, Turkey), evaluating the feasibility, safety, and efficacy of this new device. Outcomes were compared to matched patients undergoing infrapopliteal angioplasty using a paclitaxel-coated balloon (DCB).Patients and MethodsPatients with diabetes and CLTI requiring infrapopliteal intervention were recruited prospectively to undergo angioplasty and primary stenting using the Cre8 sirolimus-eluting stent between January 2018 and October 2020 at a single high-volume vascular centre; outcomes were compared to a group of patients with diabetes and CLTI who had undergone infrapopliteal angioplasty using a DCB. All patients were followed up for at least 12 months using a uniform protocol with duplex ultrasound and examination. The primary outcome measure was target lesion patency (

Rationale: There is a paucity of prospective UK studies exploring the role of Adverse Childhood Experiences (ACEs) on adolescent teenage drug use and even less is known about the complex interplay between ACEs and adolescent social, demographic, and economic characteristics. To address these gaps, we use rich longitudinal data from the nationally representative Millennium Cohort Study. Methods: Sex-stratified survey logistic regression modelling was applied using data from 9,476 adolescents and their parents to examine associations between ACEs between ages 3 and 14 years and drug use at ages 14 and 17 years. We a) explore the extent to which associations are robust to adjustment for ethnicity, family income, parental social class, and parental education, b) examine whether associations differ by these factors, and c) estimate the proportion of drug use at ages 14 and 17 years attributable to ACEs after controlling for these factors. Results: Half of MCS cohort members had been exposed to at least one ACE and approximately 1 in 11 were exposed to 3+ ACEs. Multivariable analyses suggest that ACEs were associated with a higher likelihood of drug use at age 14 than age 17, especially for girls. No evidence was found that either advantaged socio-economic position or ethnicity acted as a buffer against the negative effects of ACEs in relation to adolescent drug use. Finally, we found that prevention of exposure to sexual violence, bullying and violence within the household (if causal) is more important for girls’ drug use at age 14 than age 17. Conclusions: ACEs are associated with adolescent drug use with potential consequences on wider aspects of young people's lives, regardless of their social, ethnic, or economic background, adding further urgency to the need to reduce the incidence of these negative experiences.

We investigated how the extracellular matrix (ECM) affects LoVo colorectal cancer cells behavior during a spatiotemporal invasion. Epithelial-to-mesenchymal transition (EMT) markers, matrix-degrading enzymes, and morphological phenotypes expressed by LoVo-S (doxorubicin-sensitive) and higher aggressive LoVo-R (doxorubicin-resistant) were evaluated in cells cultured for 3 and 24 h on Millipore filters covered by Matrigel, mimicking the basement membrane, or type I Collagen reproducing a desmoplastic lamina propria. EMT and invasiveness were investigated with RT-qPCR, Western blot, and scanning electron microscopy. As time went by, most gene expressions decreased, but in type I Collagen samples, a strong reduction and high increase in MMP-2 expression in LoVo-S and -R cells occurred, respectively. These data were confirmed by the development of an epithelial morphological phenotype in LoVo-S and invading phenotypes with invadopodia in LoVo-R cells as well as by protein-level analysis. We suggest that the duration of culturing and type of substrate influence the morphological phenotype and aggressiveness of both these cell types differently. In particular, the type I collagen meshwork, consisting of large fibrils confining inter fibrillar micropores, affects the two cell types differently. It attenuates drug-sensitive LoVo-S cell aggressiveness but improves a proteolytic invasion in drug-resistant LoVo-R cells as time goes by. Experimental studies on CRC cells should examine the peri-tumoral ECM components, as well as the dynamic physical conditions of TME, which affect the behavior and aggressiveness of both drug-sensitive and drug-resistant LoVo cells differently.

Cancer-initiating cells (CICs) drive colorectal tumor growth by their supportive niches where CICs interact with multiple cell types within the microenvironment, including cancer-associated fibroblasts (CAFs). We investigated the interplay between the CICs and the clinically relevant chemotherapeutic FOLFOX that creates the persistent tumorigenic properties of colorectal CICs, and stimulates the microenvironmental factors derived from the CAFs. We found that the CICs expressing an immunophenotype (CD44v6[+]) promote FOLFOX-resistance and that the CIC-immunophenotype was enhanced by factors secreted by CAFs after FOLFOX treatment These secreted factors included periostin, IL17A and WNT3A, which induced CD44v6 expression by activating WNT3A/β-catenin signaling. Blocking the interaction between CICs with any of these CAF-derived factors through tissue-specific conditional silencing of CD44v6 significantly reduced colorectal tumorigenic potential. To achieve this, we generated two unique vectors (floxed-pSico-CD44v6 shRNA plus Fabpl-Cre) that were encapsulated into transferrin coated PEG-PEI/(nanoparticles), which when introduced in vivo reduced tumor growth more effectively than using CD44v6-blocking antibodies. Notably, this tissue-specific conditional silencing of CD44v6 resulted in long lasting effects on self-renewal and tumor growth associated with a positive feedback loop linking WNT3A signaling and alternative-splicing of CD44. These findings have crucial clinical implications suggesting that therapeutic approaches for modulating tumor growth that currently focus on cell-autonomous mechanisms may be too limited and need to be broadened to include mechanisms that recognize the interplay between the stromal factors and the subsequent CIC-immunophenotype enrichment. Thus, more specific therapeutic approaches may be required to block a chemotherapy induced remodeling of a microenvironment that acts as a paracrine regulator to enrich CD44v6 (+) in colorectal CICs

Summary: Background: Uptake of health checks among women has not been examined in relation to patient and General Practitioner (GP) practice level factors. We investigated patient and practice level factors associated with differential uptake of health checks. Methods: Primary care records from 44 practices in Lambeth for women aged 40-74 years old (N = 62,967) from 2000-2018 were analysed using multi-level logistic regression models. An odds ratio (OR) >1 indicates increased occurrence of no health check. Findings: The mean age (IQR) of the included female sample (aged 40-74 years) was 52.9 years (45.0-59.0). Adjusted for patient-level factors (age, ethnicity, English as first language, overweight/obesity, smoking, attendance to GP practices, and co-morbidity), the odds of non-uptake of health checks were higher for Other White (OR 1.24, 95% confidence interval 1.17-1.33), and Other ethnicity (1.20, 1.07-1.35) vs. White British. It was also higher for 50-69 year olds (1.55, 1.47-1.62), 70-74 year olds (1.60, 1.49-1.72) vs. 40-49 year olds. These ORs did not change on adjustments for practice level factors (proportion of patients living in deprived areas, proportion of patients with ≥1 chronic condition, ≥3 emergency diabetes admissions annually, GP density/1000 patients, quality outcome framework score of ≥ 95%, and patient satisfaction scores of ≥80%). Non-uptake was lower for Black Caribbeans, Bangladeshis, overweight/obese patients, frequent practice attenders and comorbid patients. Interpretation: Differential uptake in health checks remained after adjustment for patient and practice level factors. Better measures of social determinants of health and of practice context are needed. Funding: NIHR Research for Patient Benefit Programme (NIHR202769).

Estrogen receptors (ERs) have pivotal roles in the development and progression of triple-negative breast cancer (TNBC). Interactions among cancer cells and tumor microenvironment are orchestrated by the extracellular matrix that is rapidly emerging as prominent contributor of fundamental processes of breast cancer progression. Early studies have correlated ERβ expression in tumor sites with a more aggressive clinical outcome, however ERβ exact role in the progression of TNBC remains to be elucidated. Herein, we introduce the functional role of ERβ suppression following isolation of monoclonal cell populations of MDA-MB-231 breast cancer cells transfected with shRNA against human ESR2 that permanently resulted in 90% reduction of ERβ mRNA and protein levels. Further, we demonstrate that clone selection results in strongly reduced levels of the aggressive functional properties of MDA-MB-231 cells, by transforming their morphological characteristics, eliminating the mesenchymal-like traits of triple-negative breast cancer cells. Monoclonal populations of shERβ MDA-MB-231 cells undergo universal matrix reorganization and pass on a mesenchymal-to-epithelial transition state. These striking changes are encompassed by the total prevention of tumorigenesis in vivo following ERβ maximum suppression and isolation of monoclonal cell populations in TNBC cells. We propose that these novel findings highlight the promising role of ERβ targeting in future pharmaceutical approaches for managing the metastatic dynamics of TNBC breast cancer.

A facile experimental protocol for the synthesis of poly(ethylene glycol)-modified (PEGylated) gold nanorods (AuNRs@PEG) is presented as well as an effective drug loading procedure using the non-steroidal anti-inflammatory drug (NSAID) naproxen (NAP). The interaction of AuNRs@PEG and drug-loaded AuNRs (AuNRs@PEG@NAP) with calf-thymus DNA was studied at a diverse temperature revealing different interaction modes; AuNRs@PEG may interact via groove-binding and AuNRs@PEG@NAP may intercalate to DNA-bases. The cleavage activity of the gold nanoparticles for supercoiled circular pBR322 plasmid DNA was studied by gel electrophoresis while their affinity for human and bovine serum albumins was also evaluated. Drug-release studies revealed a pH-sensitive behavior with a release up to a maximum of 24% and 33% NAP within the first 180 min at pH = 4.2 and 6.8, respectively. The cytotoxicity of AuNRs@PEG and AuNRs@PEG@NAP was evaluated against MCF-7 and MDA-MB-231 breast cancer cell lines. The development of AuNRs as an efficient non-steroidal anti-inflammatory drugs (NSAIDs) delivery system for chemotherapy is still in its infancy. The present work can shed light and inspire other research groups to work in this direction.

Within the neurovascular unit, brain pericytes (BPs) are of major importance for the induction and maintenance of the properties of the blood-brain barrier (BBB) carried by the brain microvessel endothelial cells (ECs). Throughout barriergenesis, ECs take advantage of soluble elements or contact with BPs to maintain BBB integrity and the regulation of their cellular homeostasis. However, very few studies have focused on the role of ECs in the maturation of BPs. The aim of this study is to shed light on the proteome of BPs solocultured (hBP-solo) or cocultured with ECs (hBP-coc) to model the human BBB in a non-contact manner. We first generated protein libraries for each condition and identified 2233 proteins in hBP-solo versus 2492 in hBP-coc and 2035 common proteins. We performed a quantification of the enriched proteins in each condition by sequential window acquisition of all theoretical mass spectra (SWATH) analysis. We found 51 proteins enriched in hBP-solo related to cell proliferation, contractility, adhesion and extracellular matrix element production, a protein pattern related to an immature cell. In contrast, 90 proteins are enriched in hBP-coc associated with a reduction in contractile activities as observed in vivo in ‘mature’ BPs, and a significant gain in different metabolic functions, particularly related to mitochondrial activities and sterol metabolism. This study highlights that BPs take advantage of ECs during barriergenesis to make a metabolic switch in favor of BBB homeostasis in vitro.

Mammalian glycosaminoglycans (GAGs), except hyaluronan (HA), are sulfated polysaccharides that are covalently attached to core proteins to form proteoglycans (PGs). This article summarizes key biological findings for the most widespread GAGs, namely HA, chondroitin sulfate/dermatan sulfate (CS/DS), keratan sulfate (KS), and heparan sulfate (HS). It focuses on the major processes that remain to be deciphered to get a comprehensive view of the mechanisms mediating GAG biological functions. They include the regulation of GAG biosynthesis and postsynthetic modifications in heparin (HP) and HS, the composition, heterogeneity, and function of the tetrasaccharide linkage region and its role in disease, the functional characterization of the new PGs recently identified by glycoproteomics, the selectivity of interactions mediated by GAG chains, the display of GAG chains and PGs at the cell surface and their impact on the availability and activity of soluble ligands, and on their move through the glycocalyx layer to reach their receptors, the human GAG profile in health and disease, the roles of GAGs and particular PGs (syndecans, decorin, and biglycan) involved in cancer, inflammation, and fibrosis, the possible use of GAGs and PGs as disease biomarkers, and the design of inhibitors targeting GAG biosynthetic enzymes and GAG–protein interactions to develop novel therapeutic approaches. [ABSTRACT FROM AUTHOR]

Summary:. Palmar venous malformations are not well described in the surgical literature and are a therapeutic challenge due to the intricate anatomy of the hand. We present the case of a 19-year-old right-handed female patient from Mexico who was referred to us with a right palmar lesion present since birth, previously diagnosed as a venous malformation. The patient reported that she had undergone sclerotherapy 10 years before in addition to a prior aborted attempt at excision. Venous palmar malformations are rare occurrences. Although an individualized approach is important, the development of an algorithm may assist in the standardization of the treatment of this pathology to preserve the hand’s functional status.

Introduction:. The use of tissue oximetry for monitoring following free tissue transfer has become a common practice to facilitate early detection of poor flap perfusion. We hypothesized that T stat readings may guide fluid administration in the postoperative period and improve perfusion in patients undergoing autologous breast reconstruction. Methods:. Patients undergoing free flap breast reconstruction from 2015 to 2018 were reviewed. Mean percutaneous oximetry readings of the first four postoperative days were recorded. The mean change at 24 hours from the original reading was calculated (∆TO). The study population was divided in two groups based on whether administration of intravenous fluids (IVFs) was increased/maintained (group 1) or decreased (group 2) after postoperative day 1. Results:. A total of 120 patients were identified. The mean age was 53, and mean BMI was 33. Overall, patients for whom fluid administration was decreased experienced an increase in their tissue perfusion, while patient who received a bolus or maintained the same rate of IVF experienced a decrease. Patients who had a negative ∆TO experienced a statistically significant difference between groups 1 and 2 at 24 and 72 hours (–4 versus +3 and –11 versus +13, respectively). For patients with a positive ∆TO, although decreasing fluids resulted in higher readings, it did not reach statistical significance at 24 or 72 hours (0 versus +2 and +4 versus +6, respectively). Conclusions:. In patients undergoing free tissue breast reconstruction, tissue oximetry readings may be used as a novel guide for postoperative fluid management.

The early stages of protein misfolding and aggregation involve disordered and partially folded protein conformers that contain a high degree of dynamic disorder. These dynamic species may undergo large-scale intra-molecular motions of intrinsically disordered protein (IDP) precursors, or flexible, low affinity inter-molecular binding in oligomeric assemblies. In both cases, generating atomic level visualization of the interconverting species that captures the conformations explored and their physico-chemical properties remains hugely challenging. How specific sub-ensembles of conformers that are on-pathway to aggregation into amyloid can be identified from their aggregation-resilient counterparts within these large heterogenous pools of rapidly moving molecules represents an additional level of complexity. Here, we describe current experimental and computational approaches designed to capture the dynamic nature of the early stages of protein misfolding and aggregation, and discuss potential challenges in describing these species because of the ensemble averaging of experimental restraints that arise from motions on the millisecond timescale. We give a perspective of how machine learning methods can be used to extract aggregation-relevant sub-ensembles and provide two examples of such an approach in which specific interactions of defined species within the dynamic ensembles of α-synuclein (αSyn) and β2-microgloblulin (β2m) can be captured and investigated.