Association of Neoadjuvant Chemotherapy With Postoperative Outcomes in Immediate Prepectoral Prosthetic Breast Reconstruction.

PURPOSE: Neoadjuvant chemotherapy (NACT) followed by total mastectomy and immediate reconstruction has become an important strategy in the treatment of breast cancer. Although the safety of subpectoral implant-based breast reconstruction with NACT has been extensively evaluated, the safety in prepectoral reconstruction has not been clearly elucidated. We aimed to evaluate the association of NACT with immediate prepectoral breast reconstruction outcomes. METHODS: A retrospective review of patients who underwent total mastectomy and immediate implant-based prepectoral breast reconstruction between May and December 2021 was conducted. Patients were categorized into 2 groups: those receiving NACT and those not receiving it. Postoperative complication rates were compared between the 2 groups. The independent association between NACT and the complication profiles was evaluated. Propensity score matching was also conducted. RESULTS: We analyzed 343 cases, including 85 who received NACT treatment and 258 who did not. Compared with the non-NACT group, the NACT group was younger, had a higher body mass index, and a higher rate of adjuvant radiotherapy. There were no differences in the rates of overall complications or type of complication between the 2 groups. In the multivariable logistic analyses, NACT did not show a significant association with the development of adverse outcomes. Similar results were observed in propensity score matching analyses. CONCLUSIONS: Our results suggest that receiving NACT may not have a significant detrimental effect on the postoperative outcomes of immediate prepectoral prosthetic reconstructions. Conducting prepectoral implant-based reconstruction in the setting of NACT might be safe and provide acceptable outcomes.

Usefulness of Free Tissue Transfer for the Reconstruction of Extensive Thigh Defects.

BACKGROUND: Despite the increasing popularity of free tissue transfer, thigh defects have been alienated from their potential indication, owing to the abundance of regional reconstruction options. However, some challenging situations where locoregional modalities may lead to suboptimal outcomes often require free flap. Due to lacking studies regarding microvascular reconstruction of thigh defects, this study aimed to investigate the versatility of free tissue transfer for reconstruction of thigh defects. METHODS: A retrospective review was performed for patients who underwent microvascular reconstruction of thigh defects between 2003 and 2021. Their demographics and operation-related data were summarized and postoperative outcomes were evaluated. RESULTS: Sixty-five patients were analyzed, with a median follow-up period of 15.5 months. Most common situations requiring free tissue transfer were extensive defects, followed by large dead space with exposure of major neurovascular bundle and chronic wounds surrounded by unhealthy regional tissue. Defects were most frequently located in the anterior compartment horizontally and in the distal thigh vertically. The median surface area of the defects was 180.0 cm2. The latissimus dorsi musculocutaneous and thoracodorsal artery perforator flaps were the two most commonly used flaps. Reliable recipient vessels could generally be easily found in the vicinity of defects. Overall complications developed in 12 cases (18.5%), including two of partial flap necrosis. No total flap loss was encountered. CONCLUSION: Free tissue transfer could provide reliable outcomes and facilitate rapid recovery, and could be actively considered for reconstruction of thigh defects in situations unfavorable to the locoregional option.

Revisiting the Oxidizing Capacity of the Periodate-H2O2 Mixture: Identification of the Primary Oxidants and Their Formation Mechanisms.

This study reexamined the mechanisms for oxidative organic degradation by the binary mixture of periodate and H2O2 (PI/H2O2) that was recently identified as a new advanced oxidation process. Our findings conflicted with the previous claims that (i) hydroxyl radical (•OH) and singlet oxygen (1O2) contributed as the primary oxidants, and (ii) •OH production resulted from H2O2 reduction by superoxide radical anion (O2•-). PI/H2O2 exhibited substantial oxidizing capacity at pH < 5, decomposing organics predominantly by •OH. The likelihood of a switch in the major oxidant under varying pH conditions was revealed. IO4- as the major PI form under acidic conditions underwent one-electron reduction by H2O2 to yield radical intermediates, whereas H2I2O104- preferentially occurring at pH > 7 caused 1O2 generation through two-electron oxidation of H2O2. PI reduction by O2•- was suggested to be a key reaction in •OH production, on the basis of the electron paramagnetic resonance detection of methyl radicals in the dimethyl sulfoxide solutions containing PI and KO2, and the absence of deuterated and 18O-labeled hydroxylated intermediates during PI activation using D2O and H218O2. Finally, simple oxyanion mixing subsequent to electrochemical PI and H2O2 production achieved organic oxidation, enabling a potential strategy to minimize the use of chemicals.

Current concepts of neurofibromatosis type 1: pathophysiology and treatment.

Neurofibromatosis type 1 is the most common tumor predisposition syndrome inherited in an autosomal dominant (100% penetrance) fashion with a wide variety of expressivity. From the perspective of plastic surgery, the most significant clinical symptoms, including disfiguration, peripheral neurologic symptoms, and skeletal abnormalities, are caused by various tumors originating from the affected nerves. Surgical removal is the standard of care for these tumors. However, the outcome is frequently unsatisfactory, facilitating the search for additional therapeutic adjuvants. Current trials of molecularly targeted therapies are promising. Abbreviations: CALMs, café-au-lait macules; CNs, cutaneous neurofibromas; FDG, 18F-fluoro-deoxy-glucose; MAPK, mitogen-activated protein kinase; MPNSTs, malignant peripheral nerve sheath tumors; MRI, magnetic resonance imaging; NF1, neurofibromatosis type 1; NIH, National Institutes of Health; PET, positron emission tomography; PN, plexiform neurofibromas; TME, tumor microenvironment.

Experiences Porting NAMD to the Data Parallel C++ Programming Model.

HPC applications have a growing need to leverage heterogeneous computing resources with a vendor-neutral programming paradigm. Data Parallel C++ is a programming language based on open standards SYCL, providing a vendor-neutral solution. We describe our experiences porting the NAMD molecular dynamics application with its GPU-offload force kernels to SYCL/DPC++. Results are shown that demonstrate correctness of the porting effort.

Chloride-Mediated Enhancement in Heat-Induced Activation of Peroxymonosulfate: New Reaction Pathways for Oxidizing Radical Production.

This study is the first to demonstrate the capability of Cl- to markedly accelerate organic oxidation using thermally activated peroxymonosulfate (PMS) under acidic conditions. The treatment efficiency gain allowed heat-activated PMS to surpass heat-activated peroxydisulfate (PDS). During thermal PMS activation at excess Cl-, accelerated oxidation of 4-chlorophenol (susceptible to oxidation by hypochlorous acid (HOCl)) was observed along with significant degradation of benzoic acid and ClO3- occurrence, which involved oxidants with low substrate specificity. This indicated that heat facilitated HOCl formation via nucleophilic Cl- addition to PMS and enabled free chlorine conversion into less selective oxidizing radicals. HOCl acted as a key intermediate in the major oxidant transition based on temperature-dependent variation in HOCl concentration profiles, kinetically retarded organic oxidation upon NH4+ addition, and enabled rapid organic oxidation in heated PMS/HOCl mixtures. Chlorine atom that formed via the one-electron oxidation of Cl- by the sulfate radical served as the primary oxidant and was involved in hydroxyl radical production. This was corroborated by the quenching effects of alcohols and bicarbonates, reactivity toward multiple organics, and electron paramagnetic resonance spectral features. PMS outperformed PDS in degrading benzoic acid during thermal activation operated in reverse osmosis concentrate, which was in conflict with the well-established superiority of heat-activated PDS.

Nickel-Nickel oxide nanocomposite as a magnetically separable persulfate activator for the nonradical oxidation of organic contaminants.

The nanocomposite of metallic nickel and nickel oxide (denoted as Ni-NiO), synthesized by a simple sol-gel method, was found to activate peroxydisulfate (PDS), resulting in the effective oxidation of phenolic compounds and selected pharmaceuticals. A nonradical mechanism was proposed to explain the activation of PDS by Ni-NiO, in which organic contaminants are believed to be oxidized through an electron abstraction pathway mediated by the reactive complexes formed between PDS and the Ni-NiO surface. This mechanism was supported by multiple lines of evidence including radical scavenger experiments, the oxidation products, linear sweep voltammetry, and electron paramagnetic resonance spectroscopy. The Ni-NiO/PDS system exhibited a PDS utilization efficiency (expressed by the ratio of degraded organic contaminant to decomposed PDS) that was over 80%, and Ni-NiO showed a greater activity for PDS activation than a commercial nanoparticulate nickel oxide. This improved performance of Ni‒NiO was attributed to the disproportioned incorporation of the metallic Ni into the NiO matrix, creating more sites with oxygen vacancy. Also owing to the metallic Ni, Ni-NiO possessed magnetic properties and therefore could be easily separated and reused.

Single-Molecule Rotation for EGFR Conformational Dynamics in Live Cells.

Monitoring the dynamics of proteins in live cells on appropriate spatiotemporal scales may provide key information regarding long-standing questions in molecular and cellular regulatory mechanisms. However, tools capable of imaging the conformational changes over time have been elusive. Here, we present a single-molecule stroboscopic imaging probes by developing gyroscopic plasmonic nanoparticles, allowing for replication of protein-protein interactions and the conformational dynamics based on rotational and lateral velocities. This study fundamentally monitors the rotational motion of a membrane protein, epidermal growth factor receptor (EGFR), to decipher undiscovered structural dynamics in live cells without any molecular perturbations. This method offers a strategy to visualize assemblies and conformational changes, and provides unique insights into the mechanism underlying the molecular dynamics for receptors.

Enhancement of methane production in anaerobic digestion of sewage sludge by thermal hydrolysis pretreatment.

This study was performed to optimize thermal hydrolysis pretreatment (THP) of sewage sludge for enhanced anaerobic digestion (AD). Using the response surface methodology (RSM), the optimal conditions were found 180 °C of reaction temperature and 76 min of reaction time. Through THP under optimal conditions, high molecular substances in sewage sludge such as soluble microbial by-products (SMPs) and extracellular polymeric substances (EPSs) were hydrolyzed into low molecular ones without the generation of refractory compounds. The microbial community analysis revealed that relative abundances of Methanomicrobia such as Methanosarcina, Methanosaeta (acetoclastic methanogens), and Methanoculleus (hydrogenotrophic methanogens) in AD with THP were higher than those in conventional AD.

Autogenous fat grafting for mild-to-moderate postoperative temporal hollowing after decompressive craniectomy: One-year follow-up.

BACKGROUND: Temporal hollowing is inevitable after decompressive craniectomy. This complication affects self-perception and quality of life, and various techniques and materials have therefore been used to restore patients' confidence. Autologous fat grafting in postoperative scar tissue has been considered challenging because of the hostile tissue environment. However, in this study, we demonstrate that autologous fat grafting can be a simple and safe treatment of choice, even for postoperative depressed temporal scar tissue. METHODS: Autologous fat grafting was performed in 13 patients from 2011 to 2016. Fat was harvested according to Coleman's strategy, using a tumescent technique. Patient-reported outcomes were collected preoperatively and at 1-month and 1-year follow-ups. Photographs were taken at each visit. RESULTS: The thighs were the donor site in all cases for the first procedure. The median final volume of harvested fat was 29.4 mL (interquartile range [IQR], 24.0-32.8 mL). The median final volume of fat transferred into the temporal area was 4.9 mL on the right side (IQR, 2.5-7.1 mL) and 4.6 mL on the left side (IQR, 3.7-5.9 mL). There were no major complications. The patient-reported outcomes showed significantly improved self-perceptions at 1 month and at 1 year. CONCLUSIONS: Despite concerns about the survival of grafted fat in scar tissue, we advise autologous fat grafting for patients with temporal hollowing resulting from a previous craniectomy.

Chloride-enhanced oxidation of organic contaminants by Cu(II)-catalyzed Fenton-like reaction at neutral pH.

The Cu(II)-catalyzed Fenton-like reaction was found to be significantly accelerated in the presence of chloride ion (i.e., the Cu(II)/H2O2/Cl- system), enhancing the oxidative degradation of organic contaminants at neutral pH. The degradation of carbamazepine (a select target contaminant) by the Cu(II)/H2O2 system using 1µM Cu(II) and 10mM H2O2 was accelerated by 28-fold in the presence of 10,000mg/L Cl- at pH 7. The observed rate of carbamazepine degradation generally increased with increasing doses of Cu(II), H2O2, and Cl-, and exhibited an optimal value at around pH 7.5. Various other organic contaminants such as propranolol, phenol, acetaminophen, 4-chlorophenol, benzoic acid, and caffeine were also effectively degraded by the Cu(II)/H2O2/Cl- system. Experiments using oxidant probe compounds and electron paramagnetic spectroscopy suggested that cupryl (Cu(III)) species are the major reactive oxidants responsible for the degradation of these organic contaminants. The enhanced kinetics was further confirmed in natural seawater.

Inhibition of beta-catenin/Tcf signaling by flavonoids.

Functional activation of beta-catenin/T-cell factor (Tcf) signaling has been implicated in human carcinogenesis. We identified the inhibitory effect of various polyphenolic flavonoid compounds against beta-catenin/Tcf signaling in beta-catenin-activated cells. Genistein, kaempferol, isorhamnentin, and baicalein inhibited the transcriptional activity of beta-catenin/Tcf in HEK293 cells transiently transfected with a constitutively active mutant beta-catenin gene. To investigate the inhibitory mechanism, electrophoresis mobility shift assay, immunoprecipitation, and Western blot experiments were performed. The shift assay showed that the binding of Tcf complexes with its specific DNA-binding sites was suppressed by four kinds of flavonoids. Immunoprecipitation analysis also showed that the binding of beta-catenin to Tcf-4 was also disrupted by these flavonoids. Western blot analysis showed a decreased level of beta-catenin in nucleus caused by genistein. Genistein also decreased phosphorylation of Akt and GSK3 beta. Taken together, these results suggest that the polyphenolic flavonoids genistein, kaempferol, isorhamnentin, and baicalein are negative regulators of beta-catenin/Tcf signaling and their inhibitory mechanism is related to the decreased binding of beta-catenin/Tcf complexes to consensus DNA.