Biomechanical characterization and constitutive modeling of the layer-dissected residual strains and mechanical properties of abdominal porcine aorta.

We analyze the residual stresses and mechanical properties of layer-dissected infrarenal abdominal aorta (IAA). We measured the axial pre-stretch and opening angle and performed uniaxial tests to study and compare the mechanical behavior of both intact and layer-dissected porcine IAA samples under physiological loads. Finally, some of the most popular anisotropic hyperelastic constitutive models (GOH and microfiber models) were proposed to estimate the mechanical properties of the abdominal aorta by least-square fitting of the recorded in-vitro uniaxial test results. The results show that the residual stresses are layer dependent. In all cases, we found that the OA in the media layer is lower than in the whole artery, the intima and the adventitia. For the axial pre-stretch, we found that the adventitia and the media were slightly stretched in the environment of the intact arterial strip, whereas the intima appears to be compressed. Regarding the mechanical properties, the media seems to be the softest layer over the whole deformation domain showing high anisotropy, while the intima and adventitia exhibit considerable stiffness and a lower anisotropy response. Finally, all the hyperelastic anisotropic models considered in this study provided a reasonable approximation of the experimental data. The GOH model showed the best fitting.

Unraveling the multilayer mechanical response of aorta using layer-specific residual stresses and experimental properties.

To test the capability of the multilayer model, we used previously published layer-specific experimental data relating to the axial pre-stretch, the opening angle, the fiber distribution obtained by polarized light microscopy measurements, and the uniaxial and biaxial response of the porcine descending and abdominal aorta. We fitted the mechanical behavior of each arterial layer using Gasser, Holzapfel and Ogden strain energy function using the dispersion parameter κ as phenomenological parameter obtained during the fitting procedure or computed from the experimental fiber distribution. A multilayer finite element model of the whole aorta with the dimensions of the circumferential and longitudinal strips were then built using layer-specific material parameters previously fitted. This model was used to capture the whole aorta response under uniaxial and biaxial stress states and to reproduce the response of the whole aorta to internal pressure. Our results show that a model based on a multilayer structure without residual stresses is unable to render the uniaxial and biaxial mechanical response of the aorta (R2=0.6954 and R2=0.8582 for descending thoracic aorta (DTA) and infrarenal abdominal aorta (IAA), respectively). Only an appropriate multilayer model that includes layer-specific residual stresses can reproduce the response of the whole aorta (R2=0.9787 and R2=0.9636 for DTA and IAA respectively). In addition, a multilayer model without residual stresses produces the same stress distribution as a monolayer model without residual stresses where the maximal value of circumferential and longitudinal stresses appears at the inner radius of the intima. Finally, if layer-specific residual stresses are not available, there is less error the stress distribution using a monolayer model with residual stresses that a multilayer model without residual stresses.

Obstetric protocols in the setting of a pandemic.

The purpose of this article is to review key areas that should be considered and modified in our obstetric protocols, specifically: 1) Patient triage, 2) Labor and delivery unit policies, 3) Special considerations for personal protective equipment (PPE) needs in obstetrics, 4) Intrapartum management, and 5) Postpartum care.

A Case Report to Assess Passive Immunity in a COVID Positive Pregnant Patient.

INTRODUCTION: Data regarding transplacental passage of maternal coronavirus disease 2019 (COVID-19) antibodies and potential immunity in the newborn is limited. CASE REPORT: We present a 25-year-old multigravida with known red blood cell isoimmunization, who was found to be COVID-19 positive at 27 weeks of gestation while undergoing serial periumbilical blood sampling and intrauterine transfusions. Maternal COVID-19 antibody was detected 2 weeks after positive molecular testing. Antibodies were never detected on cord blood samples from two intrauterine fetal cord blood samples as well as neonatal cord blood at the time of delivery. CONCLUSION: This case demonstrates a lack of passive immunity of COVID-19 antibodies from a positive pregnant woman to her fetus, neither in utero nor at the time of birth. Further studies are needed to understand if passage of antibodies can occur and if that can confer passive immunity in the newborn. KEY POINTS: · Passive immunity should not be assumed in COVID-19 infection in pregnancy.. · Isoimmunization may impair passive immunity of certain antibodies.. · Vaccination to or maternal infection of COVID-19 may not be protective for the fetus..

A Survey of Labor and Delivery Practices in New York City during the COVID-19 Pandemic.

Recently, a novel coronavirus, precisely severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), that causes the disease novel coronavirus disease 2019 (COVID-19) has been declared a worldwide pandemic. Over a million cases have been confirmed in the United States. As of May 5, 2020, New York State has had over 300,000 cases and 24,000 deaths with more than half of the cases and deaths occurring in New York City (NYC). Little is known, however, of how this virus impacts pregnancy. Given this lack of data and the risk for severe disease in this relatively immunocompromised population, further understanding of the obstetrical management of COVID-19, as well as hospital level preparation for its control, is crucial. Guidance has come from expert opinion, professional societies and public health agencies, but to date, there is no report on how obstetrical practices have adapted these recommendations to their local situations. We therefore developed an internet-based survey to elucidate the practices put into place to guide the care of obstetrical patients during the COVID-19 pandemic. We surveyed obstetrical leaders in four academic medical centers in NYC who were implementing and testing protocols at the height of the pandemic. We found that all sites made changes to their practices, and that there appeared to be agreement with screening and testing for COVID-19, as well as labor and delivery protocols, for SARS-CoV-2-positive patients. We found less consensus with respect to inpatient antepartum fetal surveillance. We hope that this experience is useful to other centers as they formulate their plans to face this pandemic. KEY POINTS: · Practices changed to accommodate public health needs.. · Most practices are screened for novel COVID-19 on admission.. · Fetal testing in COVID-19 patients varied..

Failure damage mechanical properties of thoracic and abdominal porcine aorta layers and related constitutive modeling: phenomenological and microstructural approach.

Despite increasing experimental and analytical efforts to investigate the irreversible effects of arterial tissue failure, the underlying mechanisms are still poorly understood. The goal of this study was to characterize the failure properties of the intact wall and each separated layer (intima, media, and adventitia) of the descending thoracic and infrarenal abdominal aorta and to test the hypothesis that the failure properties of layer-separated tissue depend on the location of the aorta. To test this hypothesis, we performed uniaxial tests to study the mechanical behavior of both intact and layer-separated porcine aortic tissue samples taken from descending thoracic and infrarenal abdominal aorta until complete failure. The fracture stress is higher in the infrarenal abdominal aorta than in the equivalent descending thoracic aorta. It was also found that the extrapolation of the elastic mechanical properties from the physiological to the supra-physiological regime for characterizing the mechanical response of the aorta would be inappropriate. Finally, we report values of constitutive parameters using phenomenological and microstructural damage models based on continuum damage mechanics theory. The phenomenological damage model gives an excellent fit to the experimental data compared to the microstructural damage model. Although the fitting results of the phenomenological model are better, the microstructural models can include physically motivated aspects obtained from experiments.

Over length quantification of the multiaxial mechanical properties of the ascending, descending and abdominal aorta using Digital Image Correlation.

In this paper, we hypothesize that the biaxial mechanical properties of the aorta may be dependent on arterial location. To demonstrate any possible position-related difference, our study analyzed and compared the biaxial mechanical properties of the ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta stemming from the same porcine subjects, and reported values of constitutive parameters for well-known strain energy functions, showing how these mechanical properties are affected by location along the aorta. When comparing ascending thoracic aorta, descending thoracic aorta and infrarenal abdominal aorta, abdominal tissues were found to be stiffer and highly anisotropic. We found that the aorta changed from a more isotropic to a more anisotropic tissue and became progressively less compliant and stiffer with the distance to the heart. We observed substantial differences in the anisotropy parameter between aortic samples where abdominal samples were more anisotropic and nonlinear than the thoracic samples. The phenomenological model was not able to capture the passive biaxial properties of each specific porcine aorta over a wide range of biaxial deformations, showing the best prediction root mean square error ε=0.2621 for ascending thoracic samples and, especially, the worst for the infrarenal abdominal samples ε=0.3780. The micro-structured model with Bingham orientation density function was able to better predict biaxial deformations (ε=0.1372 for ascending thoracic aorta samples). The root mean square error of the micro-structural model and the micro-structured model with von Mises orientation density function were similar for all positions.

[Endoscopic bladder neck incision as first step in radical prostatectomy: An aid for patients previously treated for Bladder outlet obstruction]. / INCISIÓN ENDOSCÓPICA DEL CUELLO VESICAL COMO PRIMER PASO EN LA PROSTATECTOMÍA RADICAL: UNA AYUDA EN PACIENTES PREVIAMENTE OPERADOS POR HIPERPLASIA BENIGNA DE PRÓSTATA.

OBJECTIVE: Some patients with the indication of radical prostatectomy (RP) have often undergone previous surgical treatment for bladder outlet obstruction (BOO). These previous treatments make oncological surgery more challenging because of the difficulty in the identification of bladder neck and ureteral orifices. We present a new technique that entails previous endoscopic marking of bladder neck in order to make radical prostatectomy easier. METHODS: Twelve men with previous prostatic surgery for BOO underwent a laparoscopic/robotic radical prostatectomy between August 2008 and October 2012. The same technique was performed in all cases, a first circular endoscopic incision (EI) to mark the bladder neck and a second laparoscopic/robotic approach to complete the RP. We analyzed oncological and functional outcomes, as well as complications. RESULTS: Median operative time (EI + RP) was 175 minutes (140-205), being surgical time for endoscopic approach 20 minutes (17-31). No ureteral lesions were described and no ureteral stents were required. Positive margin rate was 8.3%. Only 1 of 5 complications observed needed surgery to be solved. Continence rate was 66.7% at one year of surgery. CONCLUSIONS: Our results show that a previous endoscopic bladder neck incision in patients with previous surgery for BOO makes easier the identification and dissection of the bladder neck itself during radical prostatectomy decreasing the risk of ureteral lesions as well as improving functional outcomes.

Incisión endoscópica del cuello vesical como primer paso en la prostatectomía radical: una ayuda en pacientes previamente operados por hiperplasia benigna de próstata / Endoscopic bladder neck incision as first step in radical prostatectomy: An aid for patients previously treated for Bladder outlet obstruction

OBJETIVO: Algunos de los pacientes a los que indicamos prostatectomía radical (PR) han sido sometidos a cirugía prostática previa por obstrucción cérvico-uretral (OCU). Este hecho dificulta la cirugía oncológica por la dificultad en la disección del cuello vesical y el riesgo de lesionar los meatos ureterales. Presentamos una técnica que consiste en realizar una incisión endoscópica previa en el cuello vesical con el fin de facilitar la prostatectomía radical. MÉTODOS: Doce pacientes con cirugía previa por OCU fueron sometidos a PR entre Agosto del 2008 y Octubre del 2012. La técnica empleada en todos los casos fue la misma, un primer tiempo endoscópico realizándose incisión endoscópica (IE) circunferencial para marcar el cuello vesical y un segundo tiempo laparoscópico/ robótico para completar la PR. Se analizaron resultados oncológicos y funcionales así como las complicaciones. RESULTADOS: La mediana del tiempo quirúrgico (IE+PR) fue de 175 (140-205) minutos, siendo la mediana de tiempo de la cirugía endoscópica 22 (17-31) minutos. No se describió en ningún caso lesiones a nivel de los meatos ureterales ni fue necesario cateterismo ureteral. La tasa de márgenes positivos fue del 8,3%. De las 5 complicaciones descritas, sólo una requirió de tratamiento quirúrgico. La continencia fue del 66,7% al año de la intervención. CONCLUSIONES: La realización de una incisión endoscópica en el cuello vesical, en pacientes con cirugía previa por OCU ha demostrado ser una buena estrategia como primer paso en la PR para conseguir buenos resultados oncológicos y funcionales junto con una baja tasa de complicaciones

OBJECTIVE: Some patients with the indication of radical prostatectomy (RP) have often undergone previous surgical treatment for bladder outlet obstruction (BOO). These previous treatments make oncological surgery more challenging because of the difficulty in the identification of bladder neck and ureteral orifices. We present a new technique that entails previous endoscopic marking of bladder neck in order to make radical prostatectomy easier. METHODS: Twelve men with previous prostatic surgery for BOO underwent a laparoscopic/robotic radical prostatectomy between August 2008 and October 2012. The same technique was performed in all cases, a first circular endoscopic incision (EI) to mark the bladder neck and a second laparoscopic/robotic approach to complete the RP. We analyzed oncological and functional outcomes, as well as complications. RESULTS: Median operative time (EI + RP) was 175 minutes (140-205), being surgical time for endoscopic approach 20 minutes (17-31). No ureteral lesions were described and no ureteral stents were required. Positive margin rate was 8.3%. Only 1 of 5 complications observed needed surgery to be solved. Continence rate was 66.7% at one year of surgery. CONCLUSIONS: Our results show that a previous endoscopic bladder neck incision in patients with previous surgery for BOO makes easier the identification and dissection of the bladder neck itself during radical prostatectomy decreasing the risk of ureteral lesions as well as improving functional outcomes

Layer-specific residual deformations and uniaxial and biaxial mechanical properties of thoracic porcine aorta.

In this paper we hypothesize that the layer-separated residual stresses and mechanical properties of layer-separated thoracic aorta arteries may be dependent on arterial location of the vessel. To demonstrate any possible position differences, we measured the axial pre-stretch and opening angle and performed uniaxial and biaxial tests under physiological loads to study the mechanical behavior of both intact and layer-separated porcine aortic samples taken from thoracic region. In addition, we also provided constitutive parameters for each layer that can be used by biomedical engineers for investigating better therapies and developing artery-specific devices. We found that the opening angle for whole artery and adventitia layer are smaller and intima greater for proximal segments than for the distal thoracic ones. For the axial pre-stretch, our results showed significant increased values of the stretch ratios with location. We found that lower thoracic samples are stiffer than upper ones with the most important differences corresponding to those between the proximal and distal behaviors in the circumferential direction. The anisotropy represented by the different circumferential and longitudinal response is more remarkable in lower thoracic aorta. Finally, adventitia and intima samples present a tendency to be stiffer and more isotropic than the corresponding media samples in both directions for upper thoracic aorta and to be more anisotropic for lower thoracic aorta.

Differential regulation of calcineurin isoforms in transplant patients: a new look at an old problem.

BACKGROUND: Calcineurin is a ubiquitously expressed calcium-dependent phosphatase that is inhibited by the immunosuppressant drugs cyclosporine and tacrolimus. Measuring calcineurin activity in transplant patients has been complicated by a lack of consistent correlation between drug level and enzyme activity, particularly with chronic use. Data from mice lacking the CnAα or CnAß isoform of the catalytic subunit of calcineurin demonstrate that loss of CnAß results in immunosuppression, whereas loss of CnAα does not. As such, methods to examine activity of the CnAß isoform may be more clinically relevant than nonspecific assays. METHODS: Because the current enzyme assays are nonisoform specific, we examined association of the CnAα or CnAß isoform with calmodulin (CaM), a shared binding protein that is only associated with the catalytic subunit in the presence of calcium. We then compared semiquantitated data with total calcineurin activity and immune status in a cohort of pretransplantation controls and postrenal transplantation patients. RESULTS: We found no difference in calcineurin activity between the groups and no difference in the amount of non-isoform-specific catalytic subunit bound to CaM. However, association of CnAα-CaM is increased in transplant patients, whereas CnAß-CaM is decreased. In addition, the amount of CnAß-CaM corresponds positively with T-cell activity and negatively with tacrolimus level. Finally, CnAß-CaM is lower in stable transplant patients compared with those with acute rejection. CONCLUSIONS: These data suggest that monitoring specifically the ß isoform may be more informative than non-isoform-specific assay methods.

Female gender and carcinoma in situ in the prostatic urethra are prognostic factors for recurrence, progression, and disease-specific mortality in T1G3 bladder cancer patients treated with bacillus Calmette-Guérin.

BACKGROUND: Controversy exists over the most important prognostic factors in T1 high-grade non-muscle-invasive bladder cancer (NMIBC) patients treated with bacillus Calmette-Guérin (BCG). OBJECTIVE: Evaluate prognostic factors for recurrence, progression, and disease-specific mortality after adjuvant intravesical BCG immunotherapy in patients with T1G3 NMIBC and long-term follow-up. DESIGN, SETTING, AND PARTICIPANTS: A single-institution retrospective analysis of 146 patients with primary stage T1G3 NMIBC. INTERVENTION: All patients were treated with complete transurethral resection (TUR) plus multiple bladder biopsies that included the prostatic urethra. No second TUR was done. Patients underwent an induction course of intravesical BCG (Connaught strain, 81mg) without maintenance therapy. MEASUREMENTS: The variables analysed for time to recurrence, progression, and death due to bladder cancer (BCa) were gender, age, tumour multiplicity, diameter, aspect, substaging, concomitant carcinoma in situ (CIS), and CIS in the prostatic urethra. Cox regression models were used to assess the univariate and multivariate prognostic importance of these factors and estimate hazard ratios (HRs). Time-to-event distributions were estimated using cumulative incidence functions. RESULTS AND LIMITATIONS: The median follow-up was 8.7 yr. Sixty-five patients (44.5%) had recurrence, 25 patients (17.1%) had progression, and 18 patients (12.3%) died because of BCa. Female gender and presence of CIS in the prostatic urethra were associated with an increased risk of recurrence (p=0.0003, HR: 2.53), progression (p=0.001, HR: 3.59), and death due to BCa (p=0.004, HR: 3.53). CONCLUSIONS: In primary T1G3 bladder tumours treated with induction BCG, female gender or having CIS in the prostatic urethra were the only prognostic factors for time to recurrence, progression, and disease-related mortality. It is very important to perform a biopsy of the prostatic urethra in patients with primary high-grade NMIBC as a first step to obtain this prognostic information.

Determinants of blood lead levels in children: a cross-sectional study in the Canary Islands (Spain).

The adverse effects of lead exposure on children are well known. Low blood lead levels (BLL) produce neurodevelopmental delay and cognitive disorders. However, since BLL thresholds for adverse effects on children's health are not known, the children population at risk of excessive lead exposure still has to be identified. This study was aimed at evaluating BLL in a children population of Gran Canaria (Canary Islands, Spain). Up to our knowledge, this is the first study to report on BLL in this population. Lead was identified and quantified in blood samples of 120 children, by means of Graphite furnace atomic absorption spectrometry (GFAAS). Lead was undetected in 80% of samples; BLL was 1 to 5 µg/dl in 15% of samples, and higher than 5 µg/dl in more than 4% of samples. BLL values in the evaluated children were low and similar to those described for other populations in Western countries. However, samples with the highest contamination (those in percentile 95) reached BLLs as high as 5.2 µg/dl. Positive associations were found between BLL and recent immigration (children adopted from non-western countries), and between BLL and parental smoking in children with low weight at birth. Since lead exposure in childhood may be a causative factor in adverse health trends - especially those involving the neurological system - and since threshold values for adverse lead effects are unknown, our finding that around 20% of the studied children had BLL higher than 1 µg/dl are of concern. Enhancing preventive measures for reducing lead exposure in children from the Canary Islands deserves further study.

Laparoscopic management of spontaneous retroperitoneal hemorrhage.

Wünderlich's syndrome is a spontaneous nontraumatic massive retroperitoneal hemorrhage. It is usually secondary to a renal neoplasm, with angiomyolipoma being the most frequent followed by renal cell carcinoma. The management of spontaneous retroperitoneal bleeding varies depending on the hemodynamic status of the patient. We present the first report of a transperitoneal laparoscopic nephrectomy in a patient with spontaneous retroperitoneal active bleeding secondary to a right renal mass.

Rescue of calcineurin Aα(-/-) mice reveals a novel role for the α isoform in the salivary gland.

Calcineurin is an important signal transduction mediator in T cells, neurons, the heart, and kidneys. Recent evidence points to unique actions of the two main isoforms of the catalytic subunit. Although the ß isoform is required for T-cell development, α is important in the brain and kidney. In addition, mice lacking α but not ß suffer from failure to thrive and early mortality. The purpose of this study was to identify the cause of postnatal death of calcineurin α null (CnAα(-/-)) mice and to determine the mechanism of α activity that contributes to the phenotype. CnAα(-/-) mice and wild-type littermate controls were fed a modified diet and then salivary gland function and histology were examined. In vitro studies were performed to identify the mechanism of α action. Data show that calcineurin is required for normal submandibular gland function and secretion of digestive enzymes. Loss of α does not impair nuclear factor of activated T-cell activity or expression but results in impaired protein trafficking downstream of the inositol trisphosphate receptor. These findings show a novel function of calcineurin in digestion and protein trafficking. Significantly, these data also provide a mechanism to rescue to adulthood a valuable animal model of calcineurin inhibitor-mediated neuronal and renal toxicities.

Loss of calcineurin Aalpha alters keratinocyte survival and differentiation.

Calcineurin is a serine/threonine phosphatase that is inhibited by the immunosuppressive drugs cyclosporine and FK506. Although calcineurin has been extensively studied in immune cells, less is known about calcineurin in other systems. There are two primary isoforms of the catalytic subunit of calcineurin, and mice have been created that lack either the alpha isoform (calcineurin A (CnA)alpha(-/-)) or the beta isoform (CnAbeta(-/-)). In this study, we examined the epidermis of CnAalpha(-/-) mice at birth and 4 weeks of age. Histological analyses revealed an attenuation of cells in the stratum spinosum of CnAalpha(-/-) mice. There was no significant difference in proliferation in the epidermis of CnAalpha(-/-) sections, but TUNEL assay revealed increased cell death in the supra-basal layers. Interestingly, the calcineurin substrate nuclear factor of activated T cells (NFATc) was highly expressed in the nucleus of basal epidermal cells in wild-type (WT) mice but was cytoplasmic in CnAalpha(-/-) mice, consistent with a loss of calcineurin activity. Moreover, NFATc activity was decreased in the epidermis of null mice compared with that in WT littermates. Finally, immunohistochemical staining revealed supra-basal expression of keratin 14 and decreased expression of differentiation-associated keratin 10 and involucrin. These findings suggest that calcineurin Aalpha activity is required for the normal differentiation and survival of epidermal cells.