Purpose
The aim of the study was to analyze the impact of neoadjuvant systemic treatment (NST) on postoperative complications and the beginning of adjuvant treatment.
Methods
This study includes data ...from a prospectively maintained database including patients with breast cancer (BC) stage I–IV with or without NST undergoing breast cancer surgery between January 2010 and September 2021.
Results
Out of 517 enrolled patients, 77 received NST, 440 had primary breast surgery. After NST patients underwent surgery after a meantime of 34 days (26.5–40 days). No statistical significance could be found comparing the complication grading according to the Clavien Dindo classification. The complications were most frequently rated as grade 3b. There were no complications with grade 4 or higher. When differentiating into short and long-term, the overall rate of short-term complications was 20.3% with no significant difference between the two groups (20.8% vs. 20.2%). Regarding long-term complications, there was more impairment of shoulder mobility (26.0% vs. 9.5%,
p
≤ 0.001) and chronic pain (42.9% vs. 28.6%,
p
≤ 0.016) for patients with NST. The beginning of the administration of the adjuvant treatment was comparable in both groups (46.3 days vs. 50.5 days).
Conclusion
In our cohort, complications between both groups were comparable according to Clavien Dindo. This study shows that NST has no negative impact on postoperative short-term complications and most importantly did not lead to a delay of the beginning of adjuvant treatment. Therefore, NST can be safely admitted, even when followed by extensive breast reconstruction surgery.
Identifying factors that can influence young peoples' physical activity and sedentary behaviors is important for the development of effective interventions. The family structure in which children ...grow up may be one such factor. As the prevalence of single parent and reconstituted families have increased substantially over the last decades, the objective of this study was to examine whether these family structures are differentially associated with young people's MVPA, participation in organized sports and screen-time activities (screen-based passive entertainment, gaming, other screen-based activities) as compared to traditional nuclear families.
The data stem from the 2013/2014 "Health Behaviour in School- aged Children (HBSC) study". A large Norwegian sample of 11-16 years old students (n = 4509) participated. Cluster-adjusted regression models were estimated using full information maximum likelihood with robust standard errors (MLR).
After adjusting for covariates, living with a single parent was negatively associated with days/week with 60 min MVPA (b = -.39, 95%CI: -.58, -.20), and positively associated with hours/weekday of total screen time (b = .50, 95%CI: .08, .93). Young people living with a single parent were also more likely to report no participation in organized sports (OR = 1.40, 95%CI: 1.09, 1.79). Living in a reconstituted family was negatively associated with days/week with 60 min MVPA (b = -.31, 95%CI: -.53, -.08), and positively associated with hours/weekday of total screen time (b = .85, 95%CI: .37, 1.33). For all outcomes, the interaction effects of family structure with sex, and with having siblings were not statistically significant. For material affluence, a significant interaction effect was found for participation in organized sports (χ
4 =13.9, p = .008). Those living in a reconstituted family with low or high material affluence had an increased risk for not participating in organized sports whereas those with medium material affluence did not.
This study suggests that living with a single parent or in reconstituted families was unfavorably associated with physical activity, sport participation and screen-based behaviors among Norwegian youth. The findings indicate that family structure could be an important factor to take into account in the development and testing of interventions. More in-depth research is needed to identify the mechanisms involved.
Transient receptor potential vanilloid 2 (TRPV2) is involved in many critical physiological and pathophysiological processes, making it a promising drug target. Here we present cryo-electron ...microscopy (cryo-EM) structures of rat TRPV2 in lipid nanodiscs activated by 2-aminoethoxydiphenyl borate (2-APB) and propose a TRPV2-specific 2-ABP binding site at the interface of S5 of one monomer and the S4-S5 linker of the adjacent monomer. In silico docking and electrophysiological studies confirm the key role of His521 and Arg539 in 2-APB activation of TRPV2. Additionally, electrophysiological experiments show that the combination of 2-APB and cannabidiol has a synergetic effect on TRPV2 activation, and cryo-EM structures demonstrate that both drugs were able to bind simultaneously. Together, our cryo-EM structures represent multiple functional states of the channel, providing a native picture of TRPV2 activation by small molecules and a structural framework for the development of TRPV2-specific activators.
Background
It has been hypothesized that bacterial biofilms on breast implants may cause chronic inflammation leading to capsular contracture. The association between bacterial biofilms of removed ...implants and capsular contracture was investigated.
Methods
Breast implants explanted between 2006 and 2010 at five participating centres for plastic and reconstructive surgery were investigated by sonication. Bacterial cultures derived from sonication were correlated with patient, surgical and implant characteristics, and the degree of capsular contracture.
Results
The study included 121 breast implants from 84 patients, of which 119 originated from women and two from men undergoing gender reassignment. Some 50 breast prostheses were implanted for reconstruction, 48 for aesthetic reasons and 23 implants were used as temporary expander devices. The median indwelling time was 4·0 (range 0·1–32) years for permanent implants and 3 (range 1–6) months for temporary devices. Excluding nine implants with clinical signs of infection, sonication cultures were positive in 40 (45 per cent) of 89 permanent implants and in 12 (52 per cent) of 23 temporary devices. Analysis of permanent implants showed that a positive bacterial culture after sonication correlated with the degree of capsular contracture: Baker I, two of 11 implants; Baker II, two of ten; Baker III, nine of 23; and Baker IV, 27 of 45 (P < 0·001). The most frequent organisms were Propionibacterium acnes (25 implants) and coagulase‐negative staphylococci (21).
Conclusion
Sonication cultures correlated with the degree of capsular contracture, indicating the potential causative role of bacterial biofilms in the pathogenesis of capsular contracture. Registration number: NCT01138891 (http://www.clinicaltrials.gov).
Subclinical infection is of major importance
We apply Fourier-transform spectral interferometry (FTSI) to study the interaction of intense laser pulses with ultrathin targets. Ultrathin submicrometer-thick solid CH targets were shot at the ...PHELIX laser facility with an intensity in the mid to upper 10^{19} W/cm^{2} range using an innovative double-pulse structure. The transmitted pulse structure was analyzed by FTSI and shows a transition from a relativistic transparency-dominated regime for targets thinner than 500 nm to a hole-boring-dominated laser-plasma interaction for thicker targets. The results also confirm that the inevitable preplasma expansion happening during the rising slope of the pulse, a few picoseconds before the maximum of the pulse is reached, cannot be neglected and plays a dominant role in laser-plasma interaction with ultrathin solid targets.
Nasal chondrocytes (NCs) have gained increased recognition for cartilage tissue regeneration. To assess NCs as a source for cell therapy treatment of intervertebral disc (IVD) degeneration, ...tissue-forming properties of NCs under physiological conditions mimicking the degenerated IVD were compared to those of mesenchymal stromal cells (MSCs) and articular chondrocytes (ACs), two cell sources presently used in clinical trials. Cells were cultured in a combination of low glucose, hypoxia, acidity and inflammation for 28 d. Depending on the conditions, cells were either cultured in the absence of instructive growth factors or underwent chondrogenic instructional priming by addition of transforming growth factor β1 (TGFβ1) for the first 7 d. Histology, immunohistochemistry, biochemistry, enzyme-linked immunosorbent assay (ELISA) and quantitative real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) analyses demonstrated limited cell maintenance and accumulation of cartilaginous extracellular matrix for MSCs in IVD conditions. ACs maintained a steady accumulation of glycosaminoglycans (GAGs) throughout all non-acidic conditions, with and without priming, but could not synthesise type II collagen (Col2). NCs accumulated both GAGs and Col2 in all non-acidic conditions, independent of priming, whereas MSCs strongly diminished their GAG and Col2 accumulation in an inflamed environment. Supplementation with inflammatory cytokines or an acidic environment affected NCs to a lower extent than ACs or MSCs. The data, overall indicating that in an inflamed IVD environment NCs were superior to ACs and MSCs, encourage further assessment of NCs for treatment of degenerative disc disease.
Abstract The emphasis on esthetic outcomes and quality of life after breast cancer surgery has motivated surgeons to develop oncoplastic breast conserving surgery (OPS). Training programs are still ...rare in most countries, and there is little standardization, which challenges the scientific evaluation of the techniques. The present article attempts to standardize OPS nomenclature, indications, and reconstruction choice selection embedded in a thorough review of the literature. We propose four breast conserving surgery (BCS) categories: Conventional tumorectomy, oncoplastic mastopexy, oncoplastic tumorectomy and oncoplastic reduction mammoplasty. The main volume displacement techniques are glandular re-approximation, use of tailored glandular or dermoglandular flaps and nipple–areola complex pedicles. We developed an indication algorithm based on the size and shape of the breast as well as the size and location of the tumor. A reconstruction algorithm suggests a selection of suitable tailored flaps and pedicles based on tumor location and vascular supply of the breast. The application of these algorithms results in known and novel OPS techniques, which are presented here with long-term results. We designed the algorithms to help tailor every operation to the individual patient in a standardized manner, since OPS is now on the rise, more than two decades after the publication of the first techniques. A rapidly increasing body of observational evidence suggests comparable rates of local recurrence between OPS and conventional BCS. Importantly, the rates of clear resection margins are in favor of OPS despite extended indications to larger tumors. Finally, OPS optimizes patient satisfaction by improving esthetic outcomes after BCS.
Preoperative imaging by Computed Tomographic Angiography (CTA) has been promoted a gold standard tool for perforator mapping in abdominally based microsurgical breast reconstruction, while Color ...Doppler Ultrasound (CDU) has lost its popularity. As the CTA X-ray exposure might have long-term consequences for patients, CDU has regained importance for preoperative workup in our center. Our aim was to revisit the role of CDU by comparing the reliability of CDU and CTA in predicting intraoperative perforator selection.
We performed a retrospective chart review study of patients who underwent microsurgical breast reconstructions with DIEP flaps at our institution. Both CTA and CDU were performed prior to the surgery, and both imaging entities were thoroughly examined by the surgical team. Perforator identification, number, size, and location were assessed and correlated with CTA and CDU data and with intraoperative findings.
We identified 98 patients who received 125 DIEP flap surgeries. A significantly stronger correlation was found between CDU and intraoperative findings of perforator detection and size (p<0.0001) and selection (r = 0.9987, CI 0.9981–0.9991, p < 0.0001 and r = 0.01, CI -0.18–0.2, p = 0.91, respectively), when compared with CTA data. If none of the preoperative imaging studies matched intraoperative perforator selection, an association with a higher incidence of flap loss (Odds ratio 4.483, CI 0.5068–39.65, p = 0.2171) was found.
Our data suggests that CDU might regain relevance as a safe and reliable preoperative imaging study, without the risk and potential consequences of X-ray exposure. Preoperative imaging tools like CDU and CTA should be considered part of the gold standard in abdominally based free flap breast reconstruction.
Pituitary endocrine cells fire action potentials (APs) to regulate their cytosolic Ca2+ concentration and hormone secretion rate. Depending on animal species, cell type, and biological conditions, ...pituitary APs are generated either by TTX-sensitive Na+ currents (INa), high-voltage activated Ca2+ currents (ICa), or by a combination of the two. Previous computational models of pituitary cells have mainly been based on data from rats, where INa is largely inactivated at the resting potential, and spontaneous APs are predominantly mediated by ICa. Unlike in rats, spontaneous INa-mediated APs are consistently seen in pituitary cells of several other animal species, including several species of fish. In the current work we develop a computational model of gonadotropin releasing cells in the teleost fish medaka (Oryzias latipes). The model stands out from previous modeling efforts by being (1) the first model of a pituitary cell in teleosts, (2) the first pituitary cell model that fires sponateous APs that are predominantly mediated by INa, and (3) the first pituitary cell model where the kinetics of the depolarizing currents, INa and ICa, are directly fitted to voltage-clamp data. We explore the firing properties of the model, and compare it to the properties of previous models that fire ICa-based APs. We put a particular focus on how the big conductance K+ current (IBK) modulates the AP shape. Interestingly, we find that IBK can prolong AP duration in models that fire ICa-based APs, while it consistently shortens the duration of the predominantly INa-mediated APs in the medaka gonadotroph model. Although the model is constrained to experimental data from gonadotroph cells in medaka, it may likely provide insights also into other pituitary cell types that fire INa-mediated APs.
Melatonin is a key hormone involved in the photoperiodic signaling pathway. In both teleosts and mammals, melatonin produced in the pineal gland at night is released into the blood and cerebrospinal ...fluid, providing rhythmic information to the whole organism. Melatonin acts
specific receptors, allowing the synchronization of daily and annual physiological rhythms to environmental conditions. The pituitary gland, which produces several hormones involved in a variety of physiological processes such as growth, metabolism, stress and reproduction, is an important target of melatonin. Melatonin modulates pituitary cellular activities, adjusting the synthesis and release of the different pituitary hormones to the functional demands, which changes during the day, seasons and life stages. It is, however, not always clear whether melatonin acts directly or indirectly on the pituitary. Indeed, melatonin also acts both upstream, on brain centers that control the pituitary hormone production and release, as well as downstream, on the tissues targeted by the pituitary hormones, which provide positive and negative feedback to the pituitary gland. In this review, we describe the known pathways through which melatonin modulates anterior pituitary hormonal production, distinguishing indirect effects mediated by brain centers from direct effects on the anterior pituitary. We also highlight similarities and differences between teleosts and mammals, drawing attention to knowledge gaps, and suggesting aims for future research.
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