Supercharged deep inferior epigastric perforator flap for reconstruction of soft tissue defect after excision of giant invasive squamous cell carcinoma of the thigh in a refractory diabetic with Pseudomonas aeruginosa infection.

Patients with large defects after oncologic surgery often require enhanced surgical planning to optimize reconstructive outcomes. As such, medically complex patients require innovative solutions when utilizing abdominal flaps due to concern for ischemia of the distal tissue. Vascular augmentations, such as supercharging or turbocharging, serve to increase perfusion in these medical complex patients to ensure flap survival. In this report, we highlight the use of a supercharged bilateral pedicled deep inferior epigastric perforator (DIEP) flap in a patient with a 231 cm2 thigh defect in the setting of uncontrolled diabetes. A 57-year-old male with poorly-controlled diabetes (blood sugar prior to surgery 510 mg/dL) and iron deficiency anemia presented with a two-year history of a large nonmetastatic squamous cell carcinoma (SCC) measuring 19 × 9 cm2 on the right thigh. Positron emission tomography/computed tomography and biopsies of the right retroperitoneal and inguinal lymph nodes diagnosed the mass as Stage 3 localized SCC. After excision, we performed immediate reconstruction of the resultant defect with a supercharged bilateral pedicled DIEP flap. The flap was pedicled on the ipsilateral DIEP and the contralateral perforator was anastomosed to the descending branch of the lateral circumflex femoral artery (DLCFA) at the inferior aspect of the defect. A venous coupler was used for the veins and the arteries were hand-sewn in end-to-end fashion. The supercharged bilateral pedicled DIEP flap was utilized for enhanced augmented perfusion to the distal edge of the pedicled flap in a high-risk patient. The patient's clinical course was complicated by a Pseudomonas infection of a small hematoma requiring operative washout and debridement of necrotic fat. However, the flap survived and covered the defect completely. The patient required outpatient antibiotics for the Pseudomonas infection which resolved completely without further need for operative intervention. At 6-month follow up, the reconstruction was stable with no tumor recurrence on clinical exam. Our results suggest that a supercharged pedicled DIEP flap may be a viable option for large defects of the thigh and can may be utilized in medically complex patients with poor capacity for wound healing.

A Non-Invasive Method for Monitoring Osteogenesis and Osseointegration Using Near-Infrared Fluorescent Imaging: A Model of Maxilla Implantation in Rats.

Currently, computed tomography and conventional X-ray radiography usually generate a micro-artifact around metal implants. This metal artifact frequently causes false positive or negative diagnoses of bone maturation or pathological peri-implantitis around implants. In an attempt to repair the artifacts, a highly specific nanoprobe, an osteogenic biomarker, and nano-Au-Pamidronate were designed to monitor the osteogenesis. In total, 12 Sprague Dawley rats were included in the study and could be chategorized in 3 groups: 4 rats in the X-ray and CT group, 4 rats in the NIRF group, and 4 rats in the sham group. A titanium alloy screw was implanted in the anterior hard palate. The X-ray, CT, and NIRF images were taken 28 days after implantation. The X-ray showed that the tissue surrounded the implant tightly; however, a gap of metal artifacts was noted around the interface between dental implants and palatal bone. Compared to the CT image, a fluorescence image was noted around the implant site in the NIRF group. Furthermore, the histological implant-bone tissue also exhibited a significant NIRF signal. In conclusion, this novel NIRF molecular imaging system precisely identifies the image loss caused by metal artifacts and can be applied to monitoring bone maturation around orthopedic implants. In addition, by observing the new bone formation, a new principle and timetable for an implant osseointegrated with bone can be established and a new type of implant fixture or surface treatment can be evaluated using this system.

Preparing Cancer Patients and Family Caregivers for Lung Surgery: Development of a Multimedia Self-Management Intervention.

The surgical treatment of lung malignancies often results in persistent symptoms, psychosocial distress, and decrements in quality of life (QOL) for cancer patients and their family caregivers (FCGs). The potential benefits of providing patients and FCGs with preparatory education that begins in the preoperative setting have been explored in multiple medical conditions, with positive impact observed on postoperative recovery, psychological distress, and QOL. However, few studies have explored the benefits of preparatory educational interventions to promote self-management in cancer surgery, including lung surgery. This paper describes the systematic approach used in the development of a multimedia self-management intervention to prepare cancer patients and their FCGs for lung surgery. Intervention development was informed by (1) contemporary published evidence on the impact of lung surgery on patients and FCG, (2) our previous research that explored QOL, symptoms, and caregiver burden after lung surgery, (3) the use of the chronic care self-management model (CCM) to guide intervention design, and (4) written comments and feedback from patients and FCGs that informed intervention development and refinement. Pilot-testing of the intervention is in process, and a future randomized trial will determine the efficacy of the intervention to improve patient, FCG, and system outcomes.

Impact of dihydrolipoic acid on mouse embryonic stem cells and related regulatory mechanisms.

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). Recently, DHLA has been used as the hydrophilic nanomaterial preparations, and therefore, determination of its bio-safety profile is essential. In this article, we show that DHLA (50-100 µM) induces apoptotic processes in mouse embryonic stem cells (ESC-B5), but exerts no injury effects at treatment dosages below 50 µM. Higher concentrations of DHLA (50-100 µM) directly increased the reactive oxygen species (ROS) content in ESC-B5 cells, along with a significant increase in cytoplasmic free calcium and nitric oxide (NO) levels, loss of mitochondrial membrane potential (MMP), activation of caspases-9 and -3, and cell death. Pretreatment with NO scavengers suppressed the apoptotic biochemical changes induced by 100 µM DHLA and promoted the gene expression levels of p53 and p21 involved in apoptotic signaling. Our results collectively indicate that DHLA at concentrations of 50-100 µM triggers apoptosis of ESC-B5 cells, which involves both ROS and NO. Importantly, at doses of less than 50 µM (0-25 µM), DHLA does not exert hazardous effects on ESC-B5 cell properties, including viability, development and differentiation. These results provide important information in terms of dosage safety and biocompatibility of DHLA to facilitate its further use as a precursor for biomaterial preparation.

Novel use and utilization of robotic Hoyer-Hook system for suspension of panniculus morbidus.

Panniculus morbidus is a complication of morbid obesity characterized by massive abdominal folds that hang below the beltline. Ulceration, dermatitis, and sinus tract formation of the pannus can cause significant morbidity to the patient and impair activities of daily living. If patients fail medical management, the next step is surgical excision. Challenging aspects of the procedure include adequate suspension of the pannus, cost, and prevention of intra-abdominal injuries. We present a case of a 70-year-old female with panniculus morbidus with endometrial carcinoma. We successfully performed a panniculectomy using a novel combination of towel hooks and the Hoyer lift to suspend the abdomen. In the same anesthesia event, she underwent robotic-assisted hysterectomy. No intra-operative or post-operative complications were encountered, and the patient was satisfied with her results. In this case, we demonstrated an effective and cost-efficient approach to panniculectomy in the severely obese patient.

Synthesis and characterization of colloidal fluorescent silver nanoclusters.

Ultrasmall water-soluble silver nanoclusters are synthesized, and their properties are investigated. The silver nanoclusters have high colloidal stability and show fluorescence in the red. This demonstrates that like gold nanoclusters also silver nanoclusters can be fluorescent.

Osteogenic differentiation is synergistically influenced by osteoinductive treatment and direct cell-cell contact between murine osteoblasts and mesenchymal stem cells.

PURPOSE: The present study was designed to address whether osteoblasts play a synergistic role in promoting mesenchymal stem cell (MSC) osteogenesis in a direct cell-cell contact co-culture model. METHODS: Murine C3H10T1/2 and MC3T3-E1 cell lines were mixed and plated onto 12-well culture plates and co-cultured at various ratios of initial cell densities. To compare the possible improvement on osteogenic differentiation, co-culture cells were served with or without osteogenic supplements in culture medium. RESULTS: Weak osteogenesis was induced in MSCs co-cultured in an untreated medium with different ratios of osteoblasts. An osteoblast-dependent increase in osteogenic gene expression of Runx2, type I collagen, and osteocalcin was observed over time. Moreover, both alkaline phosphatase (ALP) activity and calcium deposition were distinctly enhanced at levels that were proportional to the quantity of osteoblasts in the culture. The increases in mRNA expression and ALP activity were greater in co-cultures treated with osteogenic supplements than in untreated cultures. However, the production of ALP activity followed by a distinct matrix mineralization was lower in osteogenic-treated cultures containing greater numbers of osteoblasts. This suggests that a higher density of osteoblasts may lead to weak osteogenesis of MSCs by direct cell-cell contact co-culture in an untreated environment. Furthermore, additional osteogenic supplements may act synergistically with osteoblasts to accelerate matrix mineralization by reducing the process of osteogenic differentiation in osteogenic treated co-cultures. CONCLUSIONS: The present work may improve the understanding of MSC osteogenesis and may provide benefits for regenerative medicine.

Dihydrolipoic acid induces cytotoxicity in mouse blastocysts through apoptosis processes.

α-Lipoic acid (LA) is a thiol with antioxidant properties that protects against oxidative stress-induced apoptosis. LA is absorbed from the diet, taken up by cells and tissues, and subsequently reduced to dihydrolipoic acid (DHLA). In view of the recent application of DHLA as a hydrophilic nanomaterial preparation, determination of its biosafety profile is essential. In the current study, we examined the cytotoxic effects of DHLA on mouse embryos at the blastocyst stage, subsequent embryonic attachment and outgrowth in vitro, in vivo implantation by embryo transfer, and early embryonic development in an animal model. Blastocysts treated with 50 µM DHLA exhibited significantly increased apoptosis and a corresponding decrease in total cell number. Notably, the implantation success rates of blastocysts pretreated with DHLA were lower than that of their control counterparts. Moreover, in vitro treatment with 50 µM DHLA was associated with increased resorption of post-implantation embryos and decreased fetal weight. Data obtained using an in vivo mouse model further disclosed that consumption of drinking water containing 100 µM DHLA led to decreased early embryo development, specifically, inhibition of development to the blastocyst stage. However, it appears that concentrations of DHLA lower than 50 µM do not exert a hazardous effect on embryonic development. Our results collectively indicate that in vitro and in vivo exposure to concentrations of DHLA higher than 50 µM DHLA induces apoptosis and retards early pre- and post-implantation development, and support the potential of DHLA to induce embryonic cytotoxicity.

Non-surgical Management of Locally Advanced Basal Cell Carcinoma of the Upper Extremity With Vismodegib.

Basal cell carcinoma (BCC) is a common skin malignancy that can present reconstructive challenges in patients with locally advanced diseases of the extremities. This article highlights three cases of locally advanced BCC of the extremities managed with vismodegib (Erivedge, Genentech). Vismodegib is a sonic hedgehog pathway (Shh) inhibitor approved by the FDA for use in metastatic or recurrent BCC. All three patients in our case series demonstrated significant clinical responses with reductions in tumor size which obviated the need for complex reconstructive surgery or amputation.

From mono-PEGylation towards anti-nonspecific protein interaction: comparison of dihydrolipoic acid versus glutathione-capped fluorescent gold nanoclusters using gel electrophoresis.

Ultrafine fluorescent gold nanoclusters (AuNCs) have emerged as biocompatible nanoprobes for biomedical imaging in vivo, and the precision surface chemistry of AuNCs is the key for attaining their clinical application. Comparison of two promising candidates for future nanomedicine, i.e. dihydrolipoic acid- versus glutathione-capped AuNCs (AuNC@DHLA vs. AuNC@GSH), was conducted for the first time to clarify their polyethylene glycol-related bioconjugate chemistry (PEGylation) and protein interactions. Gel electrophoresis was performed to separate the number of AuNCs PEGylation, and the molecular weight of the PEG spacer dominated the resolution of the separation in the gel. We have engineered and isolated the mono-PEGylated AuNCs either from the indirect carbodiimide bioconjugate chemistry or the direct Au-S binding. One-pot synthesis showed great efficiency for isolating mono-PEGylated AuNC@GSH from the tailored controlled aggregation of Au(i)-thiolate complexes on in situ generated Au(0) cores. Post-PEGylation of AuNC@GSH was also feasible using monodendate thiol-terminated PEG, but bidendate ligands of AuNC@DHLA exhibited low PEGylated efficiency by Au-S binding. In addition, mono-PEGylated AuNC@GSH significantly enhanced the ability of anti-nonspecific protein adsorption, but mono-PEGylated AuNC@DHLA cannot avoid the nonspecific binding with serum albumin. In addition, specific nano-assembly involving mono-biotinylated AuNCs with streptavidin were also compared using gel electrophoresis. These results provide key insights into the selection, preparation and design of functional AuNCs as nanoprobes for versatile biomedical applications.

Two new, near-infrared, fluorescent probes as potential tools for imaging bone repair.

A precise imaging technique to evaluate osteogenesis, osteodifferentiation, and osseointegration following peri-implant surgery is in high clinical demand. Herein, we report the generation of two new, near-infrared (NIR) fluorescent probes for use in the molecular imaging of bone repair. The first probe aims to monitor the in vitro differentiation of human mesenchymal stem cells (MSCs) into osteoblasts. A NIR fluorochrome was conjugated to a cyclic peptide that binds to integrin α5ß1, a factor that promotes osteogenesis in MSCs and therefore functioned as an osteoblast-specific marker. The second probe aims to monitor osteogenesis, and was generated by conjugating the drug pamidronate to a NIR fluorescent gold nanocluster. Pamidronate specifically binds to hydroxyapatite (HA), a mineral present in bone that is produced by osteoblasts, and therefore provides a functional marker for new bone formation. Our results show that both probes bind to their specific targets in vitro-differentiated osteoblasts, and not to undifferentiated MSCs, and emit NIR fluorescence for functional detection. This in vitro work demonstrates the ability of these probes to bind to active osteoblasts and their mineral deposits and highlight their potential utility as clinical tools for the imaging of the osseointegration process at the molecular level.

Effects of nano calcium carbonate and nano calcium citrate on toxicity in ICR mice and on bone mineral density in an ovariectomized mice model.

Taking calcium supplements can reduce the risk of developing osteoporosis, but they are not readily absorbed in the gastrointestinal tract. Nanotechnology is expected to resolve this problem. In the present study, we examined whether the bioavailability of calcium carbonate and calcium citrate can be improved by reducing the particle size. The morphology of nano calcium carbonate and nano calcium citrate was characterized by dynamic laser-light scattering (DLS), field-emission scanning electron microscopy (FE-SEM) and transmission electron microscopy (TEM). The measurements obtained from DLS, FE-SEM and TEM were comparable. Acute and sub-chronic toxicity tests were performed to establish the safety of these products after oral administration. The no-observed-adverse-effect levels of nano calcium carbonate and nano calcium citrate were 1.3 and 2.3 g kg(-1) body weight, respectively. The results of our in vivo studies indicate that administering nano calcium carbonate and nano calcium citrate can enhance the serum calcium concentration and maintain the whole-body bone mineral density in ovariectomized mice. These data suggest that nano calcium carbonate and nano calcium citrate are more bioavailable than micro calcium carbonate and micro calcium citrate, respectively.

Tracking of cellular uptake of hydrophilic CdSe/ZnS quantum dots/hydroxyapatite composites nanoparticles in MC3T3-E1 osteoblast cells.

We report the fluorescent labeling of osteoblast cells using the biocompatible hydroxyapatite (HA) grown with nucleating seed of hydrophilic CdSe/ZnS quantum dots (QDs) allowing the real-time observation of cell under confocal microscope. We found that the MC3T3-E1 osteoblast cells can engulf HA with surface-tailored QDs showing fluorescent spots in the cytoplasm, while HA and QDs nanoparticles were not engulfed. It is interesting to see that the fluorescence was only displayed in the cytoplasm of MC3T3-E1 osteoblast cells. It can be envisioned that the nano-sized hydroxyapatite bearing fluorescent QD can only be internalized in the cytoplasm. Therefore, it is worth utilizing these composite particles to observe cellular physiology with minimal toxicity to the osteoblast cells.

Publisher Correction: Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.

Studies of photokilling of bacteria using titanium dioxide nanoparticles.

Metal pins used to apply skeletal traction or external fixation devices protruding through skin are susceptible to the increased incidence of pin site infection. In this work, we tried to establish the photokilling effects of titanium dioxide (TiO2) nanoparticles on an orthopedic implant with an in vitro study. In these photocatalytic experiments, aqueous TiO2 was added to the tested microorganism. The time effect of TiO2 photoactivation was evaluated, and the loss of viability of five different bacteria suspensions (Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Enterococcus hirae, and Bacteroides fragilis) was examined by the viable count procedure. The bactericidal effect of TiO2 nanoparticle-coated metal plates was also tested. The ultraviolet (UV) dosage used in this experiment did not affect the viability of bacteria, and all bacteria survived well in the absence of TiO2 nanoparticles. The survival curve of microorganisms in the presence of TiO2 nanoparticles showed that nearly complete killing was achieved after 50 min of UV illumination. The formation of bacterial colonies above the TiO2 nanoparticle-coated metal plates also decreased significantly. In this study, we clearly demonstrated the bactericidal effects of titanium dioxide nanoparticles. In the presence of UV light, the titanium dioxide nanoparticles can be applicable to medical facilities where the potential for infection should be controlled.

Non-Toxic Gold Nanoclusters for Solution-Processed White Light-Emitting Diodes.

Solution-processed optoelectronic devices are attractive because of the potential low-cost fabrication and the compatibility with flexible substrate. However, the utilization of toxic elements such as lead and cadmium in current optoelectronic devices on the basis of colloidal quantum dots raises environmental concerns. Here we demonstrate that white-light-emitting diodes can be achieved by utilizing non-toxic and environment-friendly gold nanoclusters. Yellow-light-emitting gold nanoclusters were synthesized and capped with trioctylphosphine. These gold nanoclusters were then blended with the blue-light-emitting organic host materials to form the emissive layer. A current efficiency of 0.13 cd/A was achieved. The Commission Internationale de l'Eclairage chromaticity coordinates of (0.27, 0.33) were obtained from our experimental analysis, which is quite close to the ideal pure white emission coordinates (0.33, 0.33). Potential applications include innovative lighting devices and monitor backlight.

Development of a biofeedback tilt-table for investigating orthostatic syncope in patients with spinal cord injury.

The purpose of this study was to develop a biofeedback tilt-table for automatic tilt-table training, helping patients with spinal cord injury (SCI) to recover more rapidly from orthostatic hypotension, and increasing safety to avoid syncope during training. This biofeedback tilt-table implemented automatic training maneuvers and included three closed feedback loops to monitor the acquisition of physiological signals from patients and the feedback of presyncope symptoms (PS) to regulate the angle of tilt. The results of clinical testing revealed that the mean blood pressure and oxygen saturation represented the most useful physiological signals for determining PS feedback and the quantitative criteria adopted were practicable and useful in describing the level of PS. This novel biofeedback tilt-table system offered higher patient throughput, faster training and safety in training of SCI patients to overcome their orthostatic hypotension than traditional tilt-table training, and could provide quantitative information of PS to assist medical staff in studying the mechanism of orthostatic syncope.

Rates and Correlates of Syphilis Reinfection in Men Who Have Sex with Men.

PURPOSE: This study examined rates and correlates of syphilis reinfection in men who have sex with men (MSM). METHODS: From 2012 to 2015, time to reinfection was assessed in 323 MSM receiving initial treatment for syphilis in San Francisco. RESULTS: One in five men was reinfected (71/323; 22%). The rate of syphilis reinfection was greater among HIV-infected men (adjusted hazard ratio [aHR] = 1.96; 95% confidence interval [95% CI] = 1.16-3.31) and ketamine users (aHR = 2.76; 95% CI = 1.09-7.00). CONCLUSION: Expanded prevention efforts are needed with HIV-infected and substance-using MSM to reduce the burden of reinfection in this population.

A Multimedia Self-management Intervention to Prepare Cancer Patients and Family Caregivers for Lung Surgery and Postoperative Recovery.

BACKGROUND: The purpose of this study was to evaluate the feasibility and acceptability of a multimedia self-management (MSM) intervention to prepare patients and family caregivers for lung surgery. PATIENTS AND METHODS: This is a quasi-experimental, 2-group, sequential enrollment pilot study of a 4-session multimedia intervention (audio/visual + print) to enhance self-management and quality of life (QOL) for patients and family caregivers. The intervention, Preparing for Lung Surgery, begins before surgery, and continues through hospitalization and discharge, with 2 telephone support sessions after discharge. Outcomes were assessed before surgery (preintervention), at discharge, and 2 to 4 weeks postdischarge (postintervention). Patient outcomes were assessed using the Functional Assessment of Cancer Therapy-General (QOL), MD Anderson Symptom Inventory and Functional Assessment of Cancer Therapy-Pulmonary Symptom Index (symptoms), self-efficacy, surgery-related knowledge, and patient activation. Family caregiver outcomes included City of Hope-QOL-Family (QOL), Caregiver Burden Scale, and knowledge. Paired t tests were used for exploratory evaluations of score changes from pre- to postintervention. RESULTS: Sixty participants (38 patients, 22 family caregivers) enrolled in the study (70% accrual). Postintervention scores were significantly improved for patients' emotional QOL (P = .001). Trends for improvements were observed for patient self-efficacy, surgery-related knowledge, and activation. Family caregivers' surgery-related knowledge was significantly improved (P = .02). Overall, participants were highly satisfied with the acceptability/usability of the intervention (3.6-3.7 of 4.0). CONCLUSION: A standardized MSM intervention was feasible and acceptable in supporting readiness and preparedness for lung surgery and postoperative recovery. A larger randomized trial is needed to verify the impact of the MSM intervention on patient/family caregiver outcomes and health care resource use.

Comparison of ultrasound and electromagnetic field effects on osteoblast growth.

This study compares the mechanisms of ultrasound (US) on osteoblast proliferation with those of pulsed electromagnetic field (PEMF), by different signal transduction pathway inhibitors. The cells were stimulated for 15 min under US or for 2 h under PEMF exposure. Twenty-four h after the beginning of stimulation, the cells were harvested and used for mitochondrial activity test (MTT) analysis. The results showed that there are different transduction pathways for US and PEMF stimulation that lead to an upgrade of osteoblast proliferation, although their pathways all lead to an increase in cytocolic Ca2+ and activation of calmodulin. These findings offer a biochemical mechanism to support the process of ultrasound and PEMF-induced enhanced healing of bone fractures.