Ruthenium complexes with mono- or bis-heterocyclic chelates: DNA/BSA binding, antioxidant and anticancer studies.

Deoxyribonucleic acid (DNA) and bovine serum albumin (BSA) binding interactions for a series of ruthenium heterocyclic complexes were monitored using ultraviolet-visible (UV-Vis) spectrophotometry, fluorescence emission spectroscopy and agarose gel electrophoresis. Investigations of the DNA interactions for the metal complexes revealed that they are groove-binders with intrinsic binding constants in the order of 104 - 107 M-1. Electronic spectrophotometric DNA titrations of the bis-heterocyclic metal complexes illustrated hypochromism of their intraligand electronic transitions and the presence of diffuse isosbestic points which are synonymous with homogeneous binding modes. Metal complexes with the mono-heterocyclic chelates also showed alterations in their intraligand transitions and changes in their metal-based electronic transitions which are suggestive of metal coordination to the CT-DNA structure. Using agarose gel electrophoresis assessments, Hoechst DNA binding competition studies corroborate that the metal complexes are DNA groove-binders. Optimal uptake of these metal complexes by BSA was observed based on their optimal apparent association and Stern-Volmer constants (Kapp and KSV > 104 M-1). Radical scavenging studies revealed that the metal complexes have high activities towards the neutralization of NO and DPPH radicals. Data attained from the BSA electronic spectrophotometric titrations for the majority of the metal complexes illustrated distinct hyperchromism accompanied with blue shifts which indicates unwinding of the protein strands. Predominately, the metal complexes showed moderate cytotoxicity against both triple-negative breast cancer and cervical cancer cell lines that was greater than that of 5-fluorouracil.Communicated by Ramaswamy H. Sarma.

Fibronectin is a stress responsive gene regulated by HSF1 in response to geldanamycin.

Fibronectin is an extracellular matrix glycoprotein with key roles in cell adhesion and migration. Hsp90 binds directly to fibronectin and Hsp90 depletion regulates fibronectin matrix stability. Where inhibition of Hsp90 with a C-terminal inhibitor, novobiocin, reduced the fibronectin matrix, treatment with an N-terminal inhibitor, geldanamycin, increased fibronectin levels. Geldanamycin treatment induced a stress response and a strong dose and time dependent increase in fibronectin mRNA via activation of the fibronectin promoter. Three putative heat shock elements (HSEs) were identified in the fibronectin promoter. Loss of two of these HSEs reduced both basal and geldanamycin-induced promoter activity, as did inhibition of the stress-responsive transcription factor HSF1. Binding of HSF1 to one of the putative HSE was confirmed by ChIP under basal conditions, and occupancy shown to increase with geldanamycin treatment. These data support the hypothesis that fibronectin is stress-responsive and a functional HSF1 target gene. COLA42 and LAMB3 mRNA levels were also increased with geldanamycin indicating that regulation of extracellular matrix (ECM) genes by HSF1 may be a wider phenomenon. Taken together, these data have implications for our understanding of ECM dynamics in stress-related diseases in which HSF1 is activated, and where the clinical application of N-terminal Hsp90 inhibitors is intended.

Transversus Abdominis Plane Blocks with Single-Dose Liposomal Bupivacaine in Conjunction with a Nonnarcotic Pain Regimen Help Reduce Length of Stay following Abdominally Based Microsurgical Breast Reconstruction.

BACKGROUND: Side effects associated with use of postoperative narcotics for pain control can delay recovery after abdominally based microsurgical breast reconstruction. The authors evaluated a nonnarcotic pain control regimen in conjunction with bilateral transversus abdominis plane blocks on facilitating early hospital discharge. METHODS: A retrospective analysis was performed of consecutive patients who underwent breast reconstruction using abdominally based free flaps, with or without being included in a nonnarcotic protocol using intraoperative transversus abdominis plane blockade. During this period, the use of locoregional analgesia evolved from none (control), to continuous bupivacaine infusion transversus abdominis plane and catheters, to single-dose transversus abdominis plane blockade with liposomal bupivacaine solution. Demographic factors, length of stay, inpatient opioid consumption, and complications were reported for all three groups. RESULTS: One hundred twenty-eight consecutive patients (182 flaps) were identified. Forty patients (62 flaps) were in the infusion-liposomal bupivacaine group, 48 (66 flaps) were in the single-dose blockade-catheter group, and 40 (54 flaps) were in the control group. The infusion-liposomal bupivacaine patients had a significantly shorter hospital stay compared with the single-dose blockade-catheter group (2.65 ± 0.66 versus 3.52 ± 0.92 days; p < 0.0001) and the control group (2.65 ± 0.66 versus 4.05 ± 1.26 days; p < 0.0001). There was no significant difference in flap loss or major complications among groups. CONCLUSIONS: When used as part of a nonnarcotic postoperative pain regimen, transversus abdominis plane blocks performed with single injections of liposomal bupivacaine help facilitate early hospital discharge after abdominally based microsurgical breast reconstruction. A trend toward consistent discharge by postoperative day 2 was seen. This could result in significant cost savings for health care systems. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Modern Perforator Flap Imaging with High-Resolution Blood Pool MR Angiography.

Advances in microsurgical techniques have improved autologous reconstructions by providing new donor site options while decreasing donor site morbidity. Various preoperative imaging modalities have been studied to assess the relevant vascular anatomic structures, with magnetic resonance (MR) angiography traditionally lagging behind computed tomography (CT) with respect to spatial resolution. Blood pool MR angiography with gadofosveset trisodium, a gadolinium-based contrast agent with extended intravascular retention, has allowed longer multiplanar acquisitions with resultant voxel sizes similar to or smaller than those of CT and with improved signal-to-noise ratio and soft-tissue contrast while maintaining the ability to depict flow with time-resolved imaging. The resultant vascular detail enables precise evaluation of the relevant vascular anatomic structures, including the vessel course, size, and branching pattern, as well as the venous arborization pattern. In addition, any architectural distortion, vessel alteration, or injury from prior surgery can be depicted. The reporting radiologist should be aware of pertinent and incidental findings relevant to the planned surgery and the patient's disease so that he or she can assist the microsurgeon in flap design as a member of the multidisciplinary team. Given the lack of ionizing radiation exposure in patients who often have an elevated body mass index, high-spatial-resolution blood pool MR angiography has become the imaging reference standard for the preoperative assessment of perforator flap vascular and soft-tissue morphology in our practice.

Factors influencing incidence and type of postmastectomy breast reconstruction in an urban multidisciplinary cancer center.

BACKGROUND: On January 1, 2011, New York State amended the Public Health Law to ensure that patients receive "information and access to breast reconstruction surgery." The purposes of this study were to investigate the early impact of this legislation on reconstruction rates and to evaluate the influence of patient variables versus physician variables on the incidence and type of breast reconstruction performed. METHODS: A retrospective study was conducted on all patients who underwent mastectomy between January 1, 2010, and December 31, 2011. Reconstruction rates were analyzed in relation to timing of legislation, breast surgeon variables, plastic surgeon faculty status, type of reconstruction, and patient variables. RESULTS: Two hundred fifty-eight patients met inclusion criteria. The overall reconstruction rate was 56.59 percent. There was no statistically significant increase in reconstruction rate after the 2011 legislation (OR, 0.45; p = 0.057). Patients whose breast surgeon was female were more likely to undergo reconstruction (OR, 5.17; p = 0.001). Patients who were Asian (OR, 0.22; p = 0.002), older than 60 years (OR, 0.09; p = 0.001), or had stage 3 and 4 cancer (OR, 0.04; p = 0.03) were less likely to undergo reconstruction. Patients reconstructed by a hospital-employed plastic surgeon were significantly more likely to undergo autologous versus implant reconstruction (OR, 6.85; p = 0.001) and to undergo microsurgical versus nonmicrosurgical autologous reconstruction (78.2 percent versus 0 percent; p = 0.001). CONCLUSIONS: Breast surgeon sex and plastic surgeon faculty status were the factors that most affected the rate and type of reconstruction, respectively. Legislation mandating the discussion of breast reconstruction options had no impact on reconstruction rate. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

The efficacy of simultaneous breast reconstruction and contralateral balancing procedures in reducing the need for second stage operations.

BACKGROUND: Patients having unilateral breast reconstruction often require a second stage procedure on the contralateral breast to improve symmetry. In order to provide immediate symmetry and minimize the frequency and extent of secondary procedures, we began performing simultaneous contralateral balancing operations at the time of initial reconstruction. This study examines the indications, safety, and efficacy of this approach. METHODS: One-hundred and two consecutive breast reconstructions with simultaneous contralateral balancing procedures were identified. Data included patient age, body mass index (BMI), type of reconstruction and balancing procedure, specimen weight, transfusion requirement, complications and additional surgery under anesthesia. Unpaired t-tests were used to compare BMI, specimen weight and need for non-autologous transfusion. RESULTS: Average patient age was 48 years. The majority had autologous tissue-only reconstructions (94%) and the rest prosthesis-based reconstructions (6%). Balancing procedures included reduction mammoplasty (50%), mastopexy (49%), and augmentation mammoplasty (1%). Average BMI was 27 and average reduction specimen was 340 grams. Non-autologous blood transfusion rate was 9%. There was no relationship between BMI or reduction specimen weight and need for transfusion. We performed secondary surgery in 24% of the autologous group and 100% of the prosthesis group. Revision rate for symmetry was 13% in the autologous group and 17% in the prosthesis group. CONCLUSIONS: Performing balancing at the time of breast reconstruction is safe and most effective in autologous reconstructions, where 87% did not require a second operation for symmetry.

A portable system for foot biomechanical analysis during gait.

Modeling the foot is challenging due to its complex structure compared to most other body segments. To analyze the biomechanics of the foot, portable devices have been designed to allow measurement of temporal, spatial, and pedobarographic parameters. The goal of this study was to design and evaluate a portable system for kinematic and dynamic analysis of the foot during gait. This device consisted of a force plate synchronized with four cameras and integrated into a walkway. The complete system can be packaged for transportation. First, the measurement system was assessed using reference objects to evaluate accuracy and precision. Second, nine healthy participants were assessed during gait trials using both the portable and Vicon systems (coupled with a force plate). The ankle and metatarsophalangeal (MP) joint angles and moments were computed, as well as the ground reaction force (GRF). The intra- and inter-subject variability was analyzed for both systems, as well as the inter-system variation. The accuracy and precision were, respectively 0.4 mm and 0.4 mm for linear values and 0.5° and 0.6° for angular values. The variability of the portable and Vicon systems were similar (i.e., the inter-system variability never exceeded 2.1°, 0.081 Nmkg(-1) and 0.267 Nkg(-1) for the angles, moments and GRF, respectively). The inter-system differences were less than the inter-subject variability and similar to the intra-subject variability. Consequently, the portable system was considered satisfactory for biomechanical analysis of the foot, outside of a motion analysis laboratory.

Foot roll-over evaluation based on 3D dynamic foot scan.

Foot roll-over is commonly analyzed to evaluate gait pathologies. The current study utilized a dynamic foot scanner (DFS) to analyze foot roll-over. The right feet of ten healthy subjects were assessed during gait trials with a DFS system integrated into a walkway. A foot sole picture was computed by vertically projecting points from the 3D foot shape which were lower than a threshold height of 15 mm. A 'height' value of these projected points was determined; corresponding to the initial vertical coordinates prior to projection. Similar to pedobarographic analysis, the foot sole picture was segmented into anatomical regions of interest (ROIs) to process mean height (average of height data by ROI) and projected surface (area of the projected foot sole by ROI). Results showed that these variables evolved differently to plantar pressure data previously reported in the literature, mainly due to the specificity of each physical quantity (millimeters vs Pascals). Compared to plantar pressure data arising from surface contact by the foot, the current method takes into account the whole plantar aspect of the foot, including the parts that do not make contact with the support surface. The current approach using height data could contribute to a better understanding of specific aspects of foot motion during walking, such as plantar arch height and the windlass mechanism. Results of this study show the underlying method is reliable. Further investigation is required to validate the DFS measurements within a clinical context, prior to implementation into clinical practice.

The use of magnetic resonance angiography in vascularized groin lymph node transfer: an anatomic study.

Vascularized groin lymph node transfer (VGLNT) has been successfully used to treat lymphedema. However, lack of familiarity with the inguinal node anatomy and concerns regarding donor site morbidity have limited its widespread use. The purpose of this study was to use magnetic resonance angiography (MRA) to clarify the inguinal anatomy and provide a reliable method for identifying the location of the superficial transverse inguinal lymph nodes. In this study MRA was used to evaluate the superficial inguinal lymph nodes in 117 patients. Coordinates of lymph nodes were plotted relative to an axis from the anterior superior iliac spine (ASIS) to the pubic tubercle (PT). The nodes were also plotted relative to the superficial circumflex iliac vein (SCIV) and superficial inferior epigastric vein (SIEV). A total of 1,938 lymph nodes were identified. These lymph nodes were concentrated on one-third the distance from the PT toward the ASIS and 3 cm perpendicularly below this line. About 67% of the superficial inguinal nodes were located within the bifurcation of the SIEV and SCIV. The results from this study provide useful guidelines for locating lymph nodes targeted for VGLNT.

Comparison of irradiated versus nonirradiated DIEP flaps in patients undergoing immediate bilateral DIEP reconstruction with unilateral postmastectomy radiation therapy (PMRT).

INTRODUCTION: Patients with node positive or locally advanced breast cancer desiring deep inferior epigastric perforator (DIEP) flap reconstruction frequently require postmastectomy radiation therapy (PMRT). To avoid the deleterious effects of PMRT, surgeons will often delay reconstruction until after PMRT is complete. Drawbacks to this approach include additional surgery, recuperation, cost, and an extended reconstructive process. Even if a tissue expander is used to preserve the skin envelope during irradiation, the post-PMRT breast pocket is often distorted or constricted necessitating some skin replacement, resulting in a compromised aesthetic outcome. Therefore, a systematic approach to mitigate the deleterious effects of PMRT was developed, and primary DIEP flap reconstruction was offered to patients requiring PMRT. This study evaluates the outcome of this approach in a cohort of patients undergoing immediate bilateral DIEP flap reconstruction with unilateral PMRT, allowing comparison between irradiated and nonirradiated flaps. METHODS: One hundred twenty-five patients who underwent immediate DIEP reconstruction between 2009 and 2011 were identified. Eleven consecutive patients had bilateral DIEP reconstructions by a single surgeon and received unilateral PMRT. Preoperative, intraoperative, and postoperative steps were taken in all patients to ensure flap vascularity, prevent uncontrolled contracture, and limit radiation damage to the breast mound. Results were documented photographically and the irradiated and nonirradiated breasts were compared. The complication rates, incidence of clinically significant fat necrosis, and need for reoperation were examined. RESULTS: Median follow-up was 18 months (range, 8-21 months). Complications were minor and did not require readmission to the hospital or reoperation. There was no incidence of clinically significant fat necrosis in either the irradiated or nonirradiated DIEP flaps. Four operative revisions for breast symmetry were required in 3 of 11 patients. Aesthetic outcomes were deemed satisfactory in all patients. CONCLUSIONS: Primary reconstruction with DIEP flaps can be performed successfully in patients who require PMRT if steps are taken to ensure flap vascularity, minimize fibrosis, optimize contour, and modulate radiation dosing.

Revision of Wise pattern breast reductions with vertical procedures.

A small percentage of patients who undergo Wise pattern mammaplasties request revisions to address recurrent macromastia or poor breast shape. Reuse of the Wise pattern method at times results in disappointing aesthetic results. Recently, in a series of 15 consecutive patients, we used vertical techniques with glandular reshaping to perform these revisions. Advantages include the ability to significantly improve breast shape and to avoid reopening of potentially problematic inframammary scars. No major complications occurred. Patients have been uniformly pleased with the significant improvement in their breast contour, width, and size. In summary, despite the use of the Wise pattern method for the original procedure, consideration should be given to use vertical techniques for revisions in that they are safe and can better address patient goals. Gratifying results can be achieved.

Bilateral breast reconstruction from a single hemiabdomen using angiosome-based flap design.

UNLABELLED: Performing bilateral autologous breast reconstruction using the abdominal donor site usually entails harvesting one flap from each hemiabdomen. However, the overlapping vascular territories of the superior epigastric, deep inferior epigastric, superficial inferior epigastric, and superficial circumflex iliac vessels make it theoretically possible to harvest two flaps based on vessels from one hemiabdomen. This may be useful in the obese patient, where one hemiabdomen may provide adequate tissue to reconstruct two breasts. The authors describe three clinical scenarios where they have used this principle, including the first reports in the literature of metachronous and synchronous bilateral breast reconstructions using two flaps based on pedicles from a single hemiabdomen. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, V.

Biomechanical maturation of joint dynamics during early childhood: updated conclusions.

Dynamic parameters have been commonly explored to characterize the biomechanical maturation of children's gaits, i.e., age-revealing joint moment and power patterns similar to adult patterns. However, the literature revealed a large disparity of conclusions about maturation depending on the study, which was most likely due to an inappropriate scaling strategy and uncontrolled walking speed. With the first years of independent walking, a large growth in height and a large variability of dimensionless walking speed are observed. Moreover, the dynamic parameters were not well studied during early childhood. In the present study, seventy-five healthy children between 1 and 6 years of age were assessed during gait trials at a self-selected speed. Four hundred and sixty-two gait trials constituting five age groups with comparable dimensionless walking speeds were selected. 3D joint moments and the power of the lower limbs were computed and expressed using a dimensionless scaling strategy (according to body weight, leg length and the acceleration of gravity). Statistical analysis was performed to examine inter-group differences. Based on the current results, we concluded the biomechanical maturation of joint dynamics occurred around an age of 4 years for the ankle and between 6 and 7 years for the knee and the hip. Moreover, age group comparisons seemed more appropriate in young children using both the dimensionless strategy and a similar walking speed. Future investigations will be conducted on an older population (i.e., adding children older than 6 years) to clearly define the status of knee and hip biomechanical maturation.

Foot mechanics during the first six years of independent walking.

Recognition of the changes during gait that occur normally as a part of growth is essential to prevent mislabeling those changes from adult gait as evidence of gait pathology. Currently, in the literature, the definition of a mature age for ankle joint dynamics is controversial (i.e., between 5 and 10 years). Moreover, the mature age of the metatarsophalangeal (MP) joint, which is essential for the functioning of the foot, has not been defined in the literature. Thus, the objective of the present study explored foot mechanics (ankle and MP joints) in young children to define a mature age of foot function. Forty-two healthy children between 1 and 6 years of age and eight adults were measured during gait. The ground reaction force (GRF), the MP and ankle joint angles, moments, powers, and 3D angles between the joint moment and the joint angular velocity vectors (3D angle α(M.ω)) were processed and compared between four age groups (2, 3.5, 5 and adults). Based on statistical analysis, the MP joint biomechanical parameters were similar between children (older than 2 years) and adults, hinting at a quick maturation of this joint mechanics. The ankle joint parameters and the GRFs (except for the frontal plane) showed an adult-like pattern in 5-year-old children. Some ankle joint parameters, such as the joint power and the 3D angle α(M.ω) still evolved significantly until 3.5 years. Based on these results, it would appear that foot maturation during gait is fully achieved at 5 years.

3D joint dynamics analysis of healthy children's gait.

The 3D joint moments and 2D joint powers have been largely explored in the literature of healthy children's gait, in particular to compare them with pathologic subjects' gait. However, no study reported on 3D joint power in children which could be due to the difficulties in interpreting the results. Recently, the analysis of the 3D angle between the joint moment and the joint angular velocity vectors has been proposed in order to help 3D joint power interpretation. Our hypothesis is that this 3D angle may help in characterizing the level of gait maturation. The present study explores 3D joint moments, 3D joint power and the proposed 3D angle for both children's and adults' gaits to highlight differences in the strategies used. The results seem to confirm that children have an alternative strategy of mainly ankle stabilization and hip propulsion compared to the adults' strategy of mainly ankle resistance and propulsion and hip stabilization. In the future, the same 3D angle analysis should be applied to different age groups for better describing the evolution of the 3D joint dynamic strategies during the growth.

Free tissue transfer in the elderly: incidence of perioperative complications following microsurgical reconstruction of 197 septuagenarians and octogenarians.

BACKGROUND: There are an increasing number of elderly patients requiring free tissue transfer. The risks of complex reconstructions in this patient population remain largely unknown. Therefore, the authors' reason for conducting this study was to review their experience with free tissue transfer in patients aged 70 years or older. METHODS: A retrospective review of all free tissue transfers performed over a 10-year period at Memorial Sloan-Kettering Cancer Center was performed and all patients aged 70 years or older were identified. Medical records and the authors' prospectively maintained database were analyzed with respect to comorbidities and postoperative complications. RESULTS: Two hundred eleven patients aged 70 years or older (70 to 79 years, n = 184; 80+ years, n = 27) were identified during the study period. Of these, 197 (70 to 79 years, n = 170; 80+ years, n = 27) patients had complete charts for review. Flap survival was 100 percent in the 80+ group and 97 percent in the 70 to 79 group. The overall complication rate was 59.3 percent in the 80+ group and 35.3 percent in the 70 to 79 group (p = 0.030). The medical complication rate was 40.7 percent in octogenarians and 11.8 percent in septuagenarians (p = 0.0004). Overall surgical complications were similar in the two groups. Univariate analysis demonstrated that age was associated with medical complications but not surgical complications. Using multivariate analysis, the authors found that alcohol use and coronary artery disease were independent predictors of overall, medical, and surgical complications. CONCLUSIONS: Free tissue transfer may be performed in patients over age 70 with a high degree of technical success. The procedure, however, carries a distinct risk of perioperative mortality and morbidity, particularly in patients over the age of 80. Comorbidities significantly associated with complications include age, alcohol use, coronary disease, and hypertension. This study suggests that prolonged survival may be achieved in some patients; however, a selective approach is required.

The effects of fungal inoculum arrangement (scale and context) on emergent community development in an agar model system.

Abstract Consequences of initial spatial organisation of model fungal communities upon their spatio-temporal development were investigated. Dynamics of prescribed two- and three-species 'communities' developing on tessellated agar tile model systems were analysed in terms of literal maps, principal component analyses, or as the proportion of species extant within tiles. It was established that for two-species interactions of equal patch size, large-scale (i.e. many constituent tiles) behaviour could be extrapolated from the relevant small-scale (i.e. pairs of tiles) interactions. However, relative patch sizes (scale) of species within tessellations influenced the times taken by individuals to colonise tiles and, hence, temporal behaviour of the system. Outcome of arrangements involving three species of equal patch size and inoculum potential, and prescribed with different mixing patterns, could not be directly extrapolated by reference to the outcome of pair-wise interactions between constituent species. Three-species arrangements attempt to limit assembly of lateral aggregates of individuals (patch size) and hence any effects of tile colonisation times, so as to reveal effects of nearest neighbour context within the complex community. Such arrangements indicate that spatial configuration of inoculum influences community development and reproducibility. They also suggest that spatial distribution of species affects persistence of individuals, which would otherwise be expected to be eliminated from the system. Two-species interactions appeared generally more reproducible than those comprising three species, and the sensitivity of fungal community development to temperature was not solely associated with influence on colony extension rate.