The Microvascular Anastomotic Coupler for Venous Anastomosis in Head and Neck Reconstruction: An Institutional Experience.

Background This study aimed to identify outcome predictors with the GEM microvascular coupler system (GEM Coupler) in a series of patients undergoing free flap reconstruction for head and neck defects. Methodology In this retrospective chart review of 218 consecutive microvascular procedures performed on 204 patients at an academic tertiary care center, demographics, comorbidities, surgical data, and outcomes were retrieved. The endpoints for the analysis were microvascular revision surgery and flap survival. Results The study included 142 (70.2%) males and 62 (29.8%) females, with a mean age of 56 years, primarily treated for malignancy (76%). The anterolateral thigh and fibula were the most commonly used flaps (40.4% and 27.1%, respectively). In 21 (9.6%) cases, a double venous anastomosis was performed. There were nine flap failures requiring microvascular revision surgery; the flap was salvaged in four of these cases yielding an overall success rate of 97.7%. Factors associated with total flap loss included a history of a thrombotic or embolic event (p = 0.017), deep circumflex iliac artery flap (p < 0.001), and absence of monitoring skin paddle (p < 0.001). Conclusions Prothrombotic conditions, buried flaps, and flap type are outcome predictors in patients undergoing microvascular reconstruction with GEM Coupler.

Supervised Automation of Cell Counting in Confocal Microscopic Cochlear Imaging Datasets Using Macro in Imaris.

Analyzing confocal microscopic data of biological samples using the Imaris software poses challenges due to its time-consuming nature involving tedious multiple steps and possibility of human errors. Here, we developed a supervised automation protocol to minimize manual input in cell and spot counting on confocal images obtained from mouse cochlear sections. The protocol increases efficiency by incorporating image recognition and object-oriented macros. Moreover, the protocol being adaptable allows scientists in diverse other fields to customize it for their specific needs.

Contribution of macrophages to neural survival and intracochlear tissue remodeling responses following cochlear implantation.

BACKGROUND: Cochlear implants (CIs) restore hearing to deafened patients. The foreign body response (FBR) following cochlear implantation (post-CI) comprises an infiltration of macrophages, other immune and non-immune cells, and fibrosis into the scala tympani, a space that is normally devoid of cells. This FBR is associated with negative effects on CI outcomes including increased electrode impedances and loss of residual acoustic hearing. This study investigates the extent to which macrophage depletion by an orally administered CSF-1R specific kinase (c-FMS) inhibitor, PLX-5622, modulates the tissue response to CI and neural health. MAIN TEXT: 10- to 12-week-old CX3CR1 + /GFP Thy1 + /YFP mice on C57BL/6J/B6 background was fed chow containing 1200 mg/kg PLX5622 or control chow for the duration of the study. 7 days after starting the diet, 3-channel cochlear implants were implanted in the ear via the round window. Serial impedance and neural response telemetry (NRT) measurements were acquired throughout the study. Electric stimulation began 7 days post-CI until 28 days post-CI for 5 h/day, 5 days/week, with programming guided by NRT and behavioral responses. Cochleae harvested at 10, 28 or 56 days post-CI were cryosectioned and labeled with an antibody against α-smooth muscle actin (α-SMA) to identify myofibroblasts and quantify the fibrotic response. Using IMARIS image analysis software, the outlines of scala tympani, Rosenthal canal, modiolus, and lateral wall for each turn were traced manually to measure region volume. The density of nuclei, CX3CR1 + macrophages, Thy1 + spiral ganglion neuron (SGN) numbers, and the ratio of the α-SMA + volume/scala tympani volume were calculated. Cochlear implantation in control diet subjects caused infiltration of cells, including macrophages, into the cochlea. Fibrosis was evident in the scala tympani adjacent to the electrode array. Mice fed PLX5622 chow showed reduced macrophage infiltration throughout the implanted cochleae across all time points. However, scala tympani fibrosis was not reduced relative to control diet subjects. Further, mice treated with PLX5622 showed increased electrode impedances compared to controls. Finally, treatment with PLX5622 decreased SGN survival in implanted and contralateral cochleae. CONCLUSION: The data suggest that macrophages play an important role in modulating the intracochlear tissue response following CI and neural survival.

Organic Functionalization of Uranyl Peroxide Clusters to Impact Solubility.

Benzene-1,2-diphosphonic acid (Ppb) was introduced into the uranyl peroxide cluster system, resulting in three Ppb-functionalized uranyl peroxide clusters, (UO2)20(O2)20(C6H4P2O6)1040- (U20Ppb10), (UO2)26(O2)33(C6H4P2O6)638- (U26Ppb6), and (UO2)20(O2)24(C6H4P2O6)632- (U20Ppb6). Dissolution experiments were performed for the potassium salts of U20Ppb10 and U26Ppb6, which revealed the capacity of U20Ppb10 to dissolve in the organic solvent dimethyl sulfoxide (DMSO). Unlike U20Ppb10, the K salt of U26Ppb6 did not dissolve in DMSO but was more soluble in water, perhaps due to the lower proportion of Ppb ligands in its structure. In this work, U20Ppb10 and U20Ppb6 formed as potassium salts and both adopt the fullerene topology of previously reported U20. U20 contains 20 uranyl peroxide units and encapsulates 12 Na cations. It is not possible for unfunctionalized U20 to incorporate 12 K cations owing to space constraints, as is the case in the new clusters reported here. Transformation of U20Ppb10 in water over time to produce U24 was observed, possibly owing to its ability to incorporate K cations, which have been associated with the formation of U24.

Design and semisynthesis of novel fredericamycin A derivatives with an improved antitumor profile.

We report the design, semisynthesis, and biological activity of a series of fredericamycin (1) derivatives. Within this series compound 1e combines low nanomolar cytotoxic potency in vitro, increased tumor cell line selectivity, and in vivo activity in a human xenograft model.