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Background: Late-onset Alzheimer's disease (LOAD) is associated with changes in certain proteins, such as ApoE and Cyp46A1, of the elimination route for cerebral cholesterol. The main lipoprotein involved in its transport is ApoE whose 4 allele is the least efficient. However, the presence or absence of this allele does not determine the development of LOAD, which implies the existence of other susceptibility factors associated with the disease, such as the CYP46A1 gene that encodes the enzyme cholesterol 24S-hydroxylase. Objective: To find new data to contribute to the evaluation of whether the presence of the T allele in the polymorphic site rs754203 of the CYP46A1 gene leads to a greater risk of developing mild cognitive impairment (MCI) and LOAD. Furthermore, given the link between APOE and CYP46A1, we proceeded to relate both genotypes in each of the patient groups studied. Methods: We studied MCI and LOAD patients and also carried out an analysis of those MCI patients who progressed from a mild cognitive deterioration to a clinically evident Alzheimer's disease during the study. Results: The frequency of the CYP46A1-T allele in the LOAD patients with APOE3 alleles is significantly higher with respect to the control group; the same occurs in the group made up of LOAD patients together with the MCI patients who progressed to LOAD. The risk of developing LOAD when this allelic combination exists is 2.262 times higher (95% CI 1.337-4.202). However, having the CYP46A1-T allele does not increase the risk of suffering from LOAD in carriers of the APOE4 allele, probably because the transport of cholesterol is already affected in such patients and possibly masks the effect of the CYP46A1-T allele. Conclusions: The CYP46A1-T allele increases the risk of suffering from LOAD in persons carrying the APOE3 allele. Copyright © 2006 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Con el objeto de determinar la época más oportuna de siembra de girasol intercalado de caña se estableció un experimento en el Ingenio Providencia en el Cerrito, (Colombia), utilizando los híbridos de girasol DO 664 Y DO 855, en seis épocas soca (10, 15,20,25,30 y 35 días) después del corte de caña CP 57603. La caña estaba sembrada entre surcos a 1.5 m y se le intercaló un surco de girasol en una población aproximada de 27 000 plantas/ha. El experimento se diseñó en bloques al azar y se arregló en parcelas divididas. En girasol se logró una producción promedia máxima de 1085 kg/ha cuando se sembró a los 10 días después del corte de la caña y decrecio el rendimiento significativamente a medida que se sembró más tarde. La siembra más aconsejable ocurrió dentro de los 10 a 25 días después de cortada la caña. El tamaño de la semilla se afectó notablemente a medida que se sembró más tarde, los porcentajes de cáscara y almendra no sufrieron variación. El diámetro del capítulo, la altura y diámetro del tallo fueron mayores en las siembras más cercanas al corte de la caña. Después de cosechado el girasol se obtuvieron 142 t/ha/ caña y 11.9 t de azúcar/ha, demostrando una recuperación total de la gramínea, lo cual se reflejó en el poco efecto que tuvo el girasol en la población, altura y diámetro final del tallo de la caña.An experiment to evaluate the most convenient planting date of sunflower intercropped in sugarcane ratoons, was carried out at the sugar mill Providencia, located at the Cerrito county (Colombia). The research included two sunflower hybrids (DO 855 and DO 664) and the sugar variety CP 57603 in six dates after of harvesting of sugarcane (10, 15, 20,25,30 and 35 days). Between the distance of the rows of sugarcane (1.50 m) an intercropped line of sunflower was planted using 4 plant per meter in a density population of 27000 plants/ha. The plot was formed by 10 rows of sunflower with 10 m long. A randomized block design was used in a split plot arrangement, where the main plots were the planting dates of sunflower and the subplots the two hybrids. The highest sunflower average yield was 1085 kg/ha when planted at 10 days after the sugarcane harvest, decreasing with following planting dates such as 147 kg/ha when planted at 35 days. The seed index had a tremendous variation with the planting date ranging from56.6 to 352 g/1000 seeds when planted at 35 days. Hull and kernel percentaje were no affected by planting date. The heads were reduced by sugarcane competition; no statistical diffence in yield was found between hybrids, the sugar cane production and sugar yield were not affected by intercropping producing 142 t/ha of cane and 11.9 t/ha of sugar. A little reduction was reported by population, heigh and diameter of cane stalks; although, was not effect found in production. The economical index showed that planting dates from 10 to 25 days were important to have good profits in sunflower intercropped in sugarcane.

Objective: Bipedalism was a significant milestone in the evolutionary development of Homo sapiens sapiens, influencing neocortical evolution and subsequent behavioral changes. Coordinated visual and sensory inputs are crucial for posture, environmental interaction, and surgical planning, with horizontal gaze being a pivotal parameter. This narrative review aims to explore various geometric measures used to assess horizontal gaze in patients, highlighting their applications in surgical planning., Methods: A literature review was conducted in indexed databases using Mesh terms like "Cervical Vertebrae" and "Visual Fields" along with keywords such as "horizontal gaze" and "sagittal spine parameters." Among 477 initially identified articles, 41 were selected for inclusion after rigorous filtering., Results: The most recognized method for assessing horizontal gaze is the Chin Brow Vertical Angle (CBVA), initially described in patients with ankylosing spondylitis. Clinical photography is employed as a tool for CBVA calculation, while other measures like McGregor slope and Slope of the Line of Sight have been considered as alternatives to CBVA. Each method presents its unique advantages and limitations., Conclusions: This review highlights the need for further research into horizontal gaze measurement methods. Developing novel approaches to determine horizontal gaze can significantly enhance surgical planning and, consequently, improve patient outcomes. The ongoing exploration of these geometric measures offers promising prospects for advancing the field and optimizing patient care., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Objective: This systematic review aims to determine the effectiveness of dorsal root ganglion stimulation (DRGS) in chronic pain management., Methods: In 2023, a comprehensive systematic review was undertaken utilizing various electronic databases, employing MeSH terms and free search terms tailored to the study's aims. This review included primary research such as cohorts, case-control studies, and clinical trials, all focusing on the efficacy of DRGS in treating various chronic pain conditions. Nonhuman or animal studies were omitted from the selection process. A review of study quality was conducted, followed by a meticulous analysis of the findings to synthesize the evidence. This review represents the most current research, with updates extending to 2024. A total of 400 articles were reviewed. Twenty-nine articles were included in our review after meticulous screening., Results: Twenty-nine articles published in the last five years meeting selection criteria were identified, encompassing patients with various diagnoses warranting the use of DRGS beyond complex regional pain syndrome. Additionally, the analysis includes different outcome measurement tools, emphasizing improvements in pain management, functionality, and quality of life. Finally, common complications such as surgical site infections and issues with electrodes are highlighted., Conclusions: This systematic review affirms the effectiveness of DRGS therapy in managing diverse chronic pain conditions, highlighting improvements in quality of life, functionality, and mood states, making it a viable alternative for patients unresponsive to traditional treatments., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The single nucleotide polymorphism (SNP) -13910 C > T has proved a good predictor of the incidence of lactase persistence in Europe and South Asia. Yet, this is not the case in the Near East, although this region is a passageway between the two continents. Lactase persistence is associated with cattle breeding, which originated in the Fertile Crescent of the Near East and spread later during the Middle Neolithic throughout Europe. Here we analyzed five SNPs (-13915 T > G (rs41380347), -13910 C > T (rs4988235), -13907 C > G (rs41525747), -14009 T > G (rs869051967), and -14010 G > C (rs145946881)) in three Jordanian human groups, namely the Bedouins, Jordan valley farmers, and Jordanian urban people. The SNPs -14009 T > G and -14010 G > C were not detected in the sample, -13907 C > G was virtually non-existent, -13910 C > T showed low frequencies, and -13915 T > G exhibited salient frequencies. The estimated incidence of lactase persistence was lower in the urban population (16 %), intermediate in the Jordan Valley's farmer population (30 %), and higher among the Bedouins (62 %). In explaining our findings, we postulated climatic change brought about by the aridification episode of the Arabian Peninsula and the Sahara 4200 years ago. This climatic milestone caused the collapse of the Akkadian Empire and the Old Kingdom in Egypt. Also, it could have led to a drastic decline of cattle in the region, being replaced by the domestication of camels. Loss of traditional crops and increasing dependence on camel milk might have triggered local selective pressures, mainly associated with -13915 T > G and differentiated from the ones in Europe, associated with -13910 C > T., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Background: Based on previous in vivo studies and human trials, intrathecal cell delivery is a safe and relevant therapeutic tool for improving patient's quality of life with neurological conditions. We aimed to characterise the safety profile of intrathecally delivered Mesenchymal stem cells (MSCs)., Methods: Ovid MEDLINE, Embase, Scopus, Cochrane Library, KCI-Korean Journal Database, and Web of Science. Databases were searched from their inception until April 13, 2023. Randomised Controlled Trials (RCTs) that compared intrathecal delivery of MSCs to controls in adult populations were included. Adverse events (AEs) were pooled and meta-analysed using DerSimonian-Laird random effects models with a correction factor 0.5 added to studies with zero count cells. Pooled AEs were described using Risk ratio (RR) and 95% confidence intervals (95% CI). Then, a random-effects meta-regress model on study-level summary data was performed to explore the relationship between the occurrence of AEs and covariates thought to modify the overall effect estimate. Finally, publication bias was assessed., Results: 303 records were reviewed, and nine RCTs met the inclusion criteria and were included in the quantitative synthesis (n = 540 patients). MSCs delivered intrathecally, as compared to controls, were associated with an increased probability of AEs of musculoskeletal and connective tissue disorders (categorised by Common Terminology Criteria for Adverse Events-CTCAE version 5.0) (RR: 1.61, 95% CI 1.19-2.19, I 2  = 0%). The random-effects meta-regress model suggested that fresh MSCs increased the probability of occurrence of AEs compared to cryopreserved MSCs (RR: 1.554; p-value = 0.048; 95% CI 1.004-2.404), and the multiple-dose, decreased the probability of AEs by 36% compared to single doses (RR: 0.644; p-value = 0.048; 95% CI 0.416-0.996); however, univariate random effects meta-regression models revealed a not significant association between the occurrence of AEs from MSCs intrathecal delivery and each covariate., Conclusions: Intrathecal delivery of MSCs was associated with a slight increase in AEs associated with musculoskeletal and connective tissue disorders, albeit without serious AEs. We conclude that intrathecal MSCs delivery is safe for patients with neurological conditions. However, further high-quality, large-scale RCTs are needed to confirm these findings., (© 2024. The Author(s).)

Several migratory waves from various origins along with cultural practices restricting marriages between people of different castes and tribes as well as continued endogamy have led to a complex and diverse society in the Indian subcontinent. Despite being widely represented in genetic studies, several interrogatives remain with regards to India's current genetic constituents and distributions, source populations and population relationships. To identify the forces that may have shaped Indian population's genetic relationships, we undertook a comprehensive comparative study of the Y-chromosomes across India utilizing Y-STR and Y-SNP chromosomal markers using the general population of Chennai in the state of Tamil Nadu as a point of reference. Our analyses identify differences in source populations for different regions within India, unique linguistic characteristics as well as demographic and cultural forces that may have shaped population structure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The chromosomal region 17q21.31 harbors a 900 kb inversion polymorphism named after the microtubule-associated protein tau (MAPT) gene. Since no recombination occurs, two haplotypes are recognized: a directly oriented variant (H1) and an inverted variant (H2). The H2 haplotype features a distribution pattern with high frequencies in the Near East and Europe, medium levels in South Asia and North Africa, and low levels elsewhere. Studies of this genomic region are relevant owing to its likely association with numerous neurodegenerative diseases. However, the causes underlying the geographic distribution of the haplotype frequencies remain a bone of contention among researchers. With this work, we have intended to outline a plausible hypothesis on the origin of the high European H2 frequencies. To that end, we have analyzed an extensive population database (including three new Iberian populations) to explore potential clinal variations of H2 frequencies. We found a sigmoidal frequency cline with an upward trend from South Asia to Europe. The maximum value was detected in the Basques from Gipuzkoa province (0.494) with the curve's inflection point in the Near East. From our results, we suggest that the most likely scenario for high H2 frequencies in Europe would be a founding event in the Near East during the late Paleolithic or early Neolithic. Subsequently, such H2 overrepresentation would have reached Europe with the arrival of the first Neolithic farmers. The current frequencies and geographic distribution of the 17q21.31 inversion suggest that the founding events mainly affected the H2D subhaplotype., (© 2022. The Author(s).)

Local treatment of bone loss with an injection of a resorbable, calcium-based implant material to replace bone has a long history of clinical use. The in vivo discrimination of changes in bone versus implant is challenging with standard computed tomography (CT). However, spectral-CT techniques enable the separation between tissues of similar densities but different chemical compositions. Dual-layer spectral-CT imaging and postprocessing analysis methods were applied to investigate the separability of AGN1 (a triphasic calcium-based implant) and bone after AGN1 injection in n = 10 male cadaveric femurs ex vivo. Using the area under the curve (AUC) from receiver-operating characteristic (ROC) analyses, the separability of AGN1 from bone was assessed for AGN1 (postoperatively) versus compact and versus femoral neck cancellous bone (both preoperatively). CT techniques included conventional Hounsfield (HU) and density-equivalent units (BMD, mg hydroxyapatite [HA]/cm 3 ) and spectral-CT measures of effective atomic number (Zeff) and electron density (ED). The samples had a wide range of femoral neck BMD (55.66 to 241.71 mg HA/cm 3 ). At the injection site average BMD, HU, Zeff, and ED increased from 69.5 mg HA/cm 3 , 109 HU, 104.38 EDW, and 8.30 Zeff in the preoperative to 1233 mg HA/cm 3 , 1741 HU, 181.27 EDW, and 13.55 Zeff in the postoperative CT scan, respectively. For compact bone at the femoral shaft the preoperative values were 1124.15 mg HA/cm 3 , 1648 HU, 177 EDW, and 13.06 Zeff and were maintained postoperatively. Zeff showed substantially sharper distributions and significantly greater separability compared to ED, BMD, and HU (all p < 0.002, for both regions) with average AUCs for BMD, HU, ED, and Zeff of 0.670, 0.640, 0.645, and 0.753 for AGN1 versus compact and 0.996, 0.995, 0.994, and 0.998 for AGN1 versus femoral neck cancellous sites, respectively. Spectral-CT permits better discrimination of calcium-based implants like AGN1 from bone ex vivo. Our results warrant application of spectral-CT in patients undergoing procedures with similar implants. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)., (© 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).)

This work provides a structural analysis of small-scale 3D-printed wind turbine ribs subjected to compression. The ribs were manufactured according to NACA 23015 and NACA 633618 geometries, with polylactic acid (PLA) and polylactic acid with carbon fiber additives (CF-PLA). In addition, holes were manufactured into the sample bodies by either 3D printing or drilling for being compared with solid samples. The compression testing was performed by following the ASTM 695D standard, whereas the beginning and propagation of delamination were assessed with the ASTM 5528 standard. Experimental results revealed that 3D-printed built-in holes provided higher compression strength, hence higher structural efficiency, than the drilled samples. Significant improvement by adding carbon fiber additives into the PLA resin system in comparison to raw PLA was detected for at least one of the studied airfoil profiles. NACA geometries also represented a key parameter for avoiding stress concentration areas, as the FEM modeling supported. However, in damaged areas, fracture mechanisms were observed such as bead-bridging, which is a key parameter in reinforcing and consolidating the specimen bodies. Working in better interphase bonding and different additives between beads and layers is highly suggested for future studies.

Additive manufacturing technologies have facilitated the construction of intricate geometries, which otherwise would be an extenuating task to accomplish by using traditional processes. Particularly, this work addresses the manufacturing, testing, and modeling of thermoplastic polyurethane (TPU) lattices. Here, a discussion of different unit cells found in the literature is presented, along with the based materials used by other authors and the tests performed in diverse studies, from which a necessity to improve the dynamic modeling of polymeric lattices was identified. This research focused on the experimental and numerical analysis of elastomeric lattices under quasi-static and dynamic compressive loads, using a Kelvin unit cell to design and build non-graded and spatially side-graded lattices. The base material behavior was fitted to an Ogden 3rd-order hyperelastic material model and used as input for the numerical work through finite element analysis (FEA). The quasi-static and impact loading FEA results from the lattices showed a good agreement with the experimental data, and by using the validated simulation methodology, additional special cases were simulated and compared. Finally, the information extracted from FEA allowed for a comparison of the performance of the lattice configurations considered herein.

Photon-counting (PC) detectors for clinical computed tomography (CT) may offer improved imaging capabilities compared to conventional energy-integrating (EI) detectors, e.g. superior spatial resolution and detective efficiency. We here investigate if PCCT can reduce the administered dose in examinations aimed at quantifying trabecular bone microstructure. Five human vertebral bodies were scanned three times in an abdomen phantom (QRM, Germany) using an experimental dual-source CT (Somatom CounT, Siemens Healthineers, Germany) housing an EI detector (0.60 mm pixel size at the iso-center) and a PC detector (0.25 mm pixel size). A tube voltage of 120 kV was used. Tube current-time product for EICT was 355 mAs (23.8 mGy CTDI 32 cm ). Dose-matched UHR-PCCT (UHRdm, 23.8 mGy) and noise-matched acquisitions (UHRnm, 10.5 mGy) were performed and reconstructed to a voxel size of 0.156 mm using a sharp kernel. Measurements of bone mineral density (BMD) and trabecular separation (Tb.Sp) and Tb.Sp percentiles reflecting the different scales of the trabecular interspacing were performed and compared to a gold-standard measurement using a peripheral CT device (XtremeCT, SCANCO Medical, Switzerland) with an isotropic voxel size of 0.082 mm and 6.6 mGy CTDI 10 cm . The image noise was quantified and the relative error with respect to the gold-standard along with the agreement between CT protocols using Lin's concordance correlation coefficient (r CCC ) were calculated. The Mean ± StdDev of the measured image noise levels in EICT was 109.6 ± 3.9 HU. UHRdm acquisitions (same dose as EICT) showed a significantly lower noise level of 78.6 ± 4.6 HU (p = 0.0122). UHRnm (44% dose of EICT) showed a noise level of 115.8 ± 3.7 HU, very similar to EICT at the same spatial resolution. For BMD the overall Mean ± StdDev for EI, UHRdm and UHRnm were 114.8 ± 28.6 mgHA/cm 3 , 121.6 ± 28.8 mgHA/cm 3 and 121.5 ± 28.6 mgHA/cm 3 , respectively, compared to 123.1 ± 25.5 mgHA/cm 3 for XtremeCT. For Tb.Sp these values were 1.86 ± 0.54 mm, 1.80 ± 0.56 mm and 1.84 ± 0.52 mm, respectively, compared to 1.66 ± 0.48 mm for XtremeCT. The ranking of the vertebrae with regard to Tb.Sp data was maintained throughout all Tb.Sp percentiles and among the CT protocols and the gold-standard. The agreement between protocols was very good for all comparisons: UHRnm vs. EICT (BMD r CCC  = 0.97; Tb.Sp r CCC  = 0.998), UHRnm vs. UHRdm (BMD r CCC  = 0.998; Tb.Sp r CCC  = 0.993) and UHRdm vs. EICT (BMD r CCC  = 0.97; Tb.Sp r CCC  = 0.991). Consequently, the relative RMS-errors from linear regressions against the gold-standard for EICT, UHRdm and UHRnm were very similar for BMD (7.1%, 5.2% and 5.4%) and for Tb.Sp (3.3%, 3.3% and 2.9%), with a much lower radiation dose for UHRnm. Short-term reproducibility for BMD measurements was similar and below 0.2% for all protocols, but for Tb.Sp showed better results for UHR (about 1/3 of the level for EICT). In conclusion, CT with UHR-PC detectors demonstrated lower image noise and better reproducibility for assessments of bone microstructure at similar dose levels. For UHRnm, radiation exposure levels could be reduced by 56% without deterioration of performance levels in the assessment of bone mineral density and bone microstructure., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier GmbH.)

Background: Topical exogenous lipase has been approved for cosmetic use and has been used to mobilize fat from adipocytes. The objective of this study was to determine the effects of exogenous lipase in the subcutaneous adipose tissue., Methods: Three different concentrations of exogenous lipase 1× (2 Units per ml), 5× (10 units per ml), and 10× (20 units per ml) were applied in a porcine model. Normal saline (NS) solution (as negative control) and phosphatidylcholine (as positive control) were also injected. Skin and subcutaneous tissue biopsies, up to the fascia, were obtained from each injection site on the 3rd day after injection. The number of cells per 20× field was counted as an indirect measurement of the size of the adipocytes., Results: For 1× lipase, the number of cells per field was 47.80 (±7.63) versus 27.26 (±4.93), and 34.66 (±6.84) for NS, and phosphatidylcholine, respectively. For 5× lipase, the count was 36.06 (±4.74) versus 24.13 (±5.18), and 33.2 (±9.34). For 10× lipase, it was 40.06 (±4.35) versus 29.26 (±2.34) and 32.66 (±6.30) (p < .05 for all groups)., Conclusions: A higher number of cells per field were observed in the lipase samples, inferring a decreased volume of adipocytes. No inflammation and/or loss of cell architecture were evidenced in the exogenous lipase groups., (© 2022 Wiley Periodicals LLC.)

General Objective: To evaluate the accuracy and validity of images with smartphone compared to the RetCam® system for the diagnosis of retinopathy of prematurity (ROP)., Methodology: Observational, longitudinal and masked study carried out at the Dr. Elías Santana hospital. Infants with birth weight ≤1500 g, gestational age ≤30 weeks and/or patients exposed to risk factors or complications linked to ROP were included. These subjects were screened using images with smartphone or RetCam®, both compared to conventional fundoscopy. The ICROP classification was used for staging. The main results analyzed were sensitivity, specificity, positive predictive values and kappa index., Results: 915 images (n = 121) were obtained, distributed in smartphone group (50.4%) and RetCam® group (49.6%) between August 2020 and March 2021. Subjects with ROP had lower gestational age (30.2 sem ± 2.8), birth weight (1361 g ± 398), and greater exposure to oxygen therapy (12.8 days ± 11.3). The RetCam® group presented sensitivity = 80%, specificity = 78%, positive predictive value = 90% and kappa index = 0.70. The smartphone group presented sensitivity = 88%, specificity = 90%, positive predictive value = 93.75% and kappa index = 0.81., Conclusions: Both diagnostic methods were accurate to identify ROP. The smartphone group obtained superior results with excellent resolution, representing a cost-effective method to create a global impact on reducing preventable blindness in the pediatric population., (Copyright © 2022 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.)

Objectives: Photon counting computed tomography (PCCT) might offer an effective spatial resolution that is significantly improved compared with conventional state-of-the-art computed tomography (CT) and even provide a microstructural level of detail similar to high-resolution peripheral CT (HR-pQCT). The aim of this study was to evaluate the volumetric effective spatial resolution of clinically approved PCCT as an alternative to HR-pQCT for ex vivo or preclinical high-resolution imaging of bone microstructure., Materials and Methods: The experiment contained 5 human vertebrae embedded in epoxy resin, which were scanned 3 times each, and on 3 different clinical CT scanners: a PCCT (Naeotom Alpha), a dual-energy CT (Somatom Force [SF]), and a single-energy CT (Somatom Sensation 40 [S40]), all manufactured by Siemens Healthineers (Erlangen, Germany). Scans were performed with a tube voltage of 120 kVp and, to provide maximum scan performance and minimum noise deterioration, with exposures of 1500 mAs (SF), 2400 mAs (S40), and 4500 mAs (PCCT) and low slice increments of 0.1 (PCCT) and 0.3 mm (SF, S40). Images were reconstructed with sharp and very sharp bone kernels, Br68 and Br76 (PCCT), Br64 (SF), and B65s and B75h (S40). Ground truth information was obtained from an XtremeCT scanner (Scanco, Brüttisellen, Switzerland). Voxel-wise comparison was performed after registration, calibration, and resampling of the volumes to isotropic voxel size of 0.164 mm. Three-dimensional point spread- and modulation-transfer functions were calculated with Wiener's deconvolution in the anatomical trabecular structure, allowing optimum estimation of device- and kernel-specific smoothing properties as well as specimen-related diffraction effects on the measurement., Results: At high contrast (modulation transfer function [MTF] of 10%), radial effective resolutions of PCCT were 10.5 lp/cm (minimum resolvable object size 476 μm) for kernel Br68 and 16.9 lp/cm (295 μm) for kernel Br76. At low contrast (MTF 5%), radial effective spatial resolutions were 10.8 lp/cm (464 μm) for kernel Br68 and 30.5 lp/cm (164 μm) for kernel Br76. Axial effective resolutions of PCCT for both kernels were between 27.0 (185 μm) and 29.9 lp/cm (167 μm). Spatial resolutions with kernel Br76 might possibly be still higher but were technically limited by the isotropic voxel size of 164 μm. The effective volumetric resolutions of PCCT with kernel Br76 ranged between 61.9 (MTF 10%) and 222.4 (MTF 5%) elements per cubic mm. Photon counting CT improved the effective volumetric resolution by factor 5.5 (MTF 10%) and 18 (MTF 5%) compared with SF and by a factor of 8.7 (MTF 10%) and 20 (MTF 5%) compared with S40. Photon counting CT allowed obtaining similar structural information as HR-pQCT., Conclusions: The effective spatial resolution of PCCT in trabecular bone imaging was comparable with that of HR-pQCT and more than 5 times higher compared with conventional CT. For ex vivo samples and when patient radiation dose can be neglected, PCCT allows imaging bone microstructure at a preclinical level of detail., Competing Interests: Conflicts of interest and sources of funding: This study was supported by a grant from the German Academic Exchange Service (DAAD). F.S.L.T. is currently receiving grants from Salesforce AI, USA, from the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (PICT 2017-1731), and from Consejo Nacional de Investigaciones Científicas y Técnicas, Argentina (PIP 2021-2023 GI). For the remaining authors, none were declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: This study aimed to assess the potential epidemiological and economic impact of rapid initiation of human immunodeficiency virus (HIV) treatment with bictegravir/emtricitabine/tenofovir alafenamide (B/F/TAF) on HIV transmission compared with the current initiation observed in clinical practice in Spain., Methods: A transmission model was adapted to estimate the cumulative HIV infection incidence and potential cost savings based on the number of HIV infections prevented among men who have sex with men, heterosexual males and females, and people who inject drugs (PWID) over a 20-year time horizon. The analysis compared rapid antiretroviral therapy (ART) initiation with B/F/TAF (9 days from diagnosis until treatment initiation) versus current ART initiation practice (with an average of 35 days from diagnosis to treatment). People living with HIV were distributed according to their treatment status. Risk for transmission was assigned to undiagnosed, diagnosed in care and not receiving ART, and receiving ART but virally unsuppressed, which was estimated by sexual contact, needles and syringes shared among PWID, state of HIV infection, and ART use., Results: In the base-case analysis, rapid ART initiation with B/F/TAF is expected to prevent 992 new HIV infections over the next 20 years compared with current ART initiation practices. Considering the lifetime costs of treating HIV infection, the reduction in HIV incidence could result in potential cost savings of €323 million., Conclusions: These results suggest that rapid ART initiation with B/F/TAF in newly diagnosed patients with HIV is a high-value strategy for the Spanish National Health System and society, reducing HIV incidence and thereby reducing future related direct and indirect costs of care., (© 2022. The Author(s).)

Background: Although some evidence suggests an association between obstructive sleep apnea (OSA) and gestational diabetes mellitus (GDM), its consequences still remain largely unknown. We sought to determine whether OSA is associated with higher inflammation and sympathetic levels in GDM, and to relate them with insulin resistance and perinatal outcomes., Methods: OSA was identified by polysomnography and defined as an apnea-hypopnea index of ≥ 5 h -1 . Plasma cytokines (TNF-α, IL-1β, IL-6, IL-8, IL-10), metanephrine, and normetanephrine were determined by immunoassays., Results: We included 17 patients with GDM and OSA and 34 without OSA. Women with GDM and OSA had higher normetanephrine concentrations [81 IQR (59-134) vs. 68 (51-81) pg/mL]. No differences in the inflammatory profile were found, while IL-1β was higher in patients with mean nocturnal oxyhemoglobin saturation ≤ 94%. We found positive correlations between increased sympathetic activation and IL-1β, with obstructive apneas, while time in REM showed an inverse relationship with IL-1β and metanephrine. Furthermore, IL-10 was inversely related with time in sleep stages 1-2, and with the arousal index, and it was positively related with time in slow-wave sleep. Significant correlations were also found between IL-1β and insulin resistance. There were no significant differences in neonatal characteristics; however, we found inverse relationships between IL-10 and birth weight (BW), and percentile of BW., Conclusions: OSA increased sympathetic activity, and IL-1β concentration was higher in patients with GDM with lower nocturnal oxygenation, all of which were related with obstructive events, and time in REM. Moreover, IL-1β was related with insulin resistance, and IL-10 inversely correlated with neonatal BW., (© 2022. The Author(s).)

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., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Frequencies of H1 and H2 haplotypes of the microtubule-associated protein tau (MAPT) gene were examined in two Jordanian samples. The criterion for haplotype assignment was the presence/absence of the intronic 238-bp deletion, located between exons 9 and 10 of the MAPT genomic region. We further compiled MAPT haplotype frequencies in Middle Eastern, South Asian, and European populations to widen the scope of analyses. Jordan MAPT*H2 haplotype frequencies peaked among worldwide samples analysed to date, with the Jordan general population featuring the top value (0.386). AMOVA tests results indicated spatial genetic structuring, as they unveiled significant differences in H2 frequencies between South Asia and Europe, with a hypothetical contact zone in the Middle East. The southeastern region of the Middle East shares low H2 frequencies with South Asia, while the northwestern area shows high H2 frequencies, similar to and even higher than observed in Europe. We suggest that high H2 frequencies could have originated at the beginning of the Neolithic in the western region of the Middle East, most likely through genetic drift episodes associated with founding events. Subsequently, the arrival of Neolithic farmers boosted the H2 haplotype spreading throughout Europe.

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 (R 2 =0.6954 and R 2 =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 (R 2 =0.9787 and R 2 =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., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

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.., Competing Interests: None declared., (Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.)

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.

Objectives: This study aimed to explore the diversity of paternal lineages in Jujuy province (Argentina) by analyzing Y chromosome markers. Furthermore, we examined among-population genetic variability based both on paternally (NRY haplotypes) and maternally (mtDNA haplogroups) inherited markers. We sought to evaluate the impact of sex-biased gene flow on genetic background in Jujuy, and contribute data on the microevolutionary forces acting in this zone., Methods: DNA from 149 males from five Jujuy regions were analyzed for 12 non-recombining Y (NRY) markers. Genetic heterogeneity among Jujuy regions was evaluated through population differentiation tests. To identify potential genetic boundaries in Jujuy, analysis of molecular variance (AMOVA) and the Monmonier's algorithm implemented in the Barrier v2.2 software were employed., Results: A clear divergence between Jujuy highlands and lowlands for NRY haplotypes was found. A marked discrepancy between genetic structuring for paternal lineages and the lack of geographical pattern for mitogenomes was confirmed by all statistical analyses., Conclusions: Genetic structuring of paternal lineages is most likely caused by admixture processes that have occurred since colonial times in the Jujuy lowlands. Immigrants were predominantly male that settled in the lower altitude zones, due to the steep orography of the region. Input of allochthonous male lineages because of gene flow toward the lowlands would have increased diversity of NRY markers, thus compensating for drift effects. Likewise, limited input of allochthonous mitogenomes would have promoted genetic drift, a key factor in the shaping of diversity of maternal lineages across Jujuy subpopulations, irrespective of altitude., (© 2019 Wiley Periodicals, Inc.)

Vertebral whole bone strength is substantially affected by cortical bone properties. Disease and therapy may affect cancellous and cortical bone differently. Unlike Dual X-ray Absorptiometry (DXA), Quantitative Computed Tomography (QCT) permits selective assessment of cortical and cancellous bone, but image quality limits the accuracy. We present an image processing method specifically adopted to thin cortices that substantially improves accuracy. Ten human vertebrae embedded in epoxy resin were imaged using clinical QCT and High-Resolution QCT (HR-QCT) protocols, both acquired on a clinical whole body CT scanner, whereas high resolution peripheral QCT (HR-pQCT) was used as gold standard. Microstructural variables and BMD were calculated using in-house software StructuralInsight for QCT and HR-QCT and the manufacturer's μCT evaluation software for HR-pQCT. An adjusted measure, a deconvolved cortical thickness (dcCt.Th), corrected for partial volume effects, was derived applying the new Iterative Convolution OptimizatioN (ICON) method. Direct measurements of cortical thickness (Ct.Th) showed substantial overestimation with mean ± standard deviation of 1.8 ± 0.5 mm for QCT and 1.5 ± 0.3 mm for HR-QCT compared to 0.37 ± 0.07 mm using HR-pQCT. Correlations of both QCT (r 2  = 0.05, p > 0.5.) and HR-QCT (r 2  = 0.38, p = 0.060) with the gold standard HR-pQCT were not significant. Also QCT-based BMD and BMC as well as HR-QCT-based BMD did not show a significant correlation with the gold standard approach. Only HR-QCT-based BMC showed a modest correlation (r 2  = 0.59, p = 0.01) After applying ICON corrections, dcCt.Th resulted in 0.52 ± 0.09 mm for QCT and 0.43 ± 0.07 mm for HR-QCT, both significantly correlated to HR-pQCT (r 2  = 0.75, p = 0.0012 and r 2  = 0.93, p < 0.0001, respectively). The average overestimation bias of Ct.Th was reduced from (402 ± 157)% to (45 ± 17)% for QCT and from (330 ± 69)% to (19 ± 8)% for HR-QCT. Due to inaccurate segmentation uncorrected QCT-based Ct.Th measures as well as BMD and BMC showed no correlation to HR-pQCT and thus such bias cortical data can be misleading. The application of ICON reduced random overestimation bias to about 50 μm and 20 μm for QCT and HR-QCT, respectively, leading to a recovery of a significant correlation with the reference data of HR-pQCT. This reveals the potential for fairly accurate assessment of cortical thickness, allowing to better characterize cortical mechanical competence. These results warrant testing of the performance in vivo., (Copyright © 2018 Elsevier Inc. All rights reserved.)

In this work, fundamental symmetric Lamb wave S0 mode is characterized in terms of its velocity variation as function of the interfacial conditions between solid bodies in contact. Imperfect contact conditions are numerically and experimentally determined by using ultrasonic Lamb wave propagation parameters. For the study, an experimental system was used, formed by two solid aluminum rods (25.4mm in diameter) axially loading a thin aluminum plate to control contact interfacial stiffness. The axially applied load on the aluminum plate was varied from 0MPa to 10MPa. Experimental Lamb wave signals were excited on the plate through two longitudinal contact transducers (1MHz of central frequency) using a pitch-catch configuration. Numerical simulations of contact conditions and Lamb wave propagation were performed through Finite Element Analysis (FEA) in commercial software, ANSYS 15®. Simulated Lamb wave signals were generated by means of a 5 cycles tone burst signals with different frequency values. Results indicate a velocity change in both, experimental and simulated Lamb wave signals as function of the applied load. Finally, a comparison between numerical results and experimental measurements was performed obtaining a good agreement., (Copyright © 2017 Elsevier B.V. All rights reserved.)

We examined tau haplotype frequencies in two different ethnical groups from the Basque Country (BC): Roma people and residents of European ancestry (general population). In addition, we analyzed the spatial distribution of tau haplotypes in Eurasian populations to explore the genetic affinities of the Romani groups living in Europe in a broader scope. The 17q21.31 genomic region was characterized through the genotyping of two diagnostic single nucleotide polymorphisms, SNPs (rs10514879 and rs199451), which allow the identification of H1 and H2 haplotypes. A significant heterozygous deficit was detected in the Romani for rs10514879. The H2 haplotype frequency proved to be more than twice in the BC general population (0.283) than in the Roma people (0.127). In contrast, H2 frequency proved to be very similar between Basque and Hungarian Romani, and similar to the H2 frequencies found in northwestern India and Pakistan as well. Several statistical analyses unveiled genetic structuring for the MAPT diversity, mirrored in a significant association between geography and genetic distances, with an upward trend of H2 haplotype frequencies from Asia to Europe. Yet, Roma samples did not fit into this general spatial patterning because of their discrepancy between geographical position and H2 frequency. Despite the long spatial coexistence in the Basque region between the residents of European ancestry and the Roma, the latter have preserved their Asian genetic ancestry. Bearing in mind the lack of geographical barriers between both ethnical groups, these findings support the notion that sociocultural mores might promote assortative matings in human populations.

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., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: To examine the association of ophthalmic artery (OA) Doppler measure - the ratio of velocity peaks (PR) - to adverse pregnancy outcomes in preeclampsia., Study Design and Main Outcomes: Prospective cohort study of 56 women with preeclampsia that underwent Doppler measurements of OA flow, medial to optic nerve. PR results were classified as normal (PR < 0.78), abnormal (PR 0.78-0.98), or highly abnormal (PR ≥ 0.99). Attending clinicians were blinded to OA Doppler results. The primary endpoints were (1) a composite of adverse maternal outcomes-central nervous system injury (eclampsia or posterior reversible encephalopathy syndrome), HELLP syndrome, hypertensive crisis, maternal admission to the intensive care unit, and maternal death-and (2) a composite of adverse perinatal outcomes-birth weight <10th percentile for gestational age, neonatal acidemia, 5-min Apgar score <7, admission of infants weighing >2500 g to the neonatal intensive care, preterm birth <32 weeks, fetal or neonatal death., Results: Adverse maternal outcomes became more frequent as the PR values increased (p=.005). The occurrence of hypertensive crisis after hospital admission (secondary endpoint) was also positively associated with PR values (p=.001). Adverse perinatal outcomes were not associated with PR values (p=.551), but women in the highly abnormal PR group (PR ≥ 0.99) had the earliest deliveries (p=.001) and the smallest newborns (p=.004). All women in the highly abnormal PR group (n=16) had an adverse outcome., Conclusions: Maternal OA Doppler PR ≥ 0.99 in preeclampsia may identify women at increased risk of adverse maternal outcomes and pregnancies at the greatest risk of preterm birth., (Copyright © 2017 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objective: To evaluate the risk of long-term tumor recurrence and progression in patients with low- and intermediate-risk non-muscle-invasive bladder cancers, which could facilitate optimization in the follow-up schedules., Materials and Methods: A single-institution, retrospective analysis of 704 patients with primary TaG1, TaG2, T1G1, and T1G2 urothelial carcinomas of the bladder without concomitant carcinoma in situ, treated with transurethral resection, was performed. Response was determined and monitored by routine periodic urine cytology, cystoscopy, and upper tract imaging., Results: The median follow-up was 64.9 months (maximum, 120 months). Among all of the tumors, 59.3% did not relapse, 36.6% recurred in the bladder during the first 5 years of surveillance, and only 3.6% recurred after 5 years of follow-up. Eight urothelial bladder cancers (1.1%) progressed in stage, and 87.5% of the progressions occurred during the first 5 years of surveillance. An upper urinary tract recurrence was detected in 2.4% of the patients; 94.1% were diagnosed within the upper urinary tract during the first 5 years of follow-up and 5.9% occurred after 5 years of surveillance., Conclusion: G1-2 urothelial bladder cancers recur and progress uncommonly in the long-term period. Although limited by its retrospective nature, the present study provides potential grounds for re-examination of the follow-up schedule for patients with primary non-muscle-invasive bladder cancer G1-2 tumors who remain asymptomatic and disease-free for at least 5 years., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Multiple myeloma (MM) is a malignant plasma cell disease associated with severe bone destruction. Surgical intervention is often required to prevent vertebral body collapse and resulting neurological complications; however, its necessity is determined by measuring lesion size or number, without considering bone biomechanics. Finite element (FE) modeling, which simulates the physiological loading, may improve the prediction of fragility. To test this, we developed a quantitative computed tomography (QCT)-based FE model of the vertebra and applied it to a dataset of MM patients with and without prevalent fracture. FE models were generated from vertebral QCT scans of the T 12 (T 11 if T 12 was fractured) of 104 MM patients, 45 with fracture and 59 without, using a low-dose scan protocol (1.5 mm slice thickness, 4.0 to 6.5 mSv effective dose). A calibration phantom enabled the conversion of the CT Hounsfield units to FE material properties. Compressive loading of the vertebral body was simulated and the stiffness, yield load, and work to yield determined. To compare the parameters between fracture and nonfracture groups, t tests were used, and standardized odds ratios (sOR, normalized to standard deviation) and 95% confidence intervals were calculated. FE parameters were compared to mineral and structural parameters using linear regression. Patients with fracture showed lower vertebral stiffness (-15.2%; p = 0.010; sOR = 1.73; 95% CI, 1.11 to 2.70), yield force (-21.5%; p = 0.002; sOR = 2.09; 95% CI, 1.27 to 3.43), and work to yield (-27.4%; p = 0.001; sOR = 2.28; 95% CI, 1.33 to 3.92) compared to nonfracture patients. All parameters correlated significantly with vBMD (stiffness: R 2  = 0.57, yield force: R 2  = 0.59, work to yield: R 2  = 0.50, p < 0.001), BV/TV (stiffness: R 2  = 0.56, yield force: R 2  = 0.58, work to yield: R 2  = 0.49, p < 0.001), and Tb.Sp (stiffness: R 2  = 0.51, yield force: R 2  = 0.53, work to yield: R 2  = 0.45, p < 0.001). FE modeling identified MM patients with compromised mechanical integrity of the vertebra. Higher sOR values were obtained for the biomechanical compared to structural or mineral measures, suggesting that FE modeling improves fragility assessment in these patients. © 2016 American Society for Bone and Mineral Research., (© 2016 American Society for Bone and Mineral Research.)

Purpose: Existing microstructure parameters are able to predict vertebral in vitro failure load, but for noisy in vivo data more complex algorithms are needed for a robust assessment., Methods: A new algorithm is proposed for the microstructural analysis of trabecular bone under in vivo quantitative computed tomography (QCT). Five fractal parameters are computed: (1) the average local fractal dimension FD, (2) its standard deviation FD.SD, (3) the fractal rod volume ratio fRV/BV, (4) the average fractal trabecular thickness fTb.Th, and (5) its coefficient of variation fTb.Th.CV. The algorithm requires neither an explicit skeletonization of the trabecular bone, nor a well-defined transition between bone and marrow phases. Two experiments were conducted to compare the fractal with established microstructural parameters. In the first, 20 volumes-of-interest of embedded vertebrae phantoms were scanned five times under QCT and high-resolution (HR-)QCT and once under peripheral HRQCT (HRpQCT), to derive accuracy and precision. In the second experiment, correlations between in vitro HRQCT structural parameters were obtained from 76 human T 11 , T 12 , or L 1 vertebrae. In vitro fracture data were available for a subset of 17 human T 12 vertebrae so that linear regression models between failure load and microstructural HRQCT parameters could be analyzed., Results: The results showed correlations of fTb.Th and fRV/BV with their nonfractal pendants trabecular thickness (Tb.Th) and respective structure model index (SMI) while higher precision and accuracy was observed on the fractal measures. Linear models of bone mineral density with two and three fractal microstructural HRQCT parameters explained 86% and 90% (adjusted R 2 ) of the failure load and significantly improved the linear models based only on BMD and established standard microstructural parameters (68%-77% adjusted R 2 )., Conclusions: The application of fractal methods may grant further insight into the study of bone quality in vivo when image resolution and quality are less than optimal for current standard methods.

Background: A ureteroileal anastomosis stricture (UAS) is one of the most frequent complications after radical cystectomy. Open surgical repair is the treatment of choice but is associated with morbidity., Objective: To describe the efficacy and safety of laparoscopic management for benign secondary UAS., Design, Setting, and Participants: A review was performed of the 11 initial procedures performed at our academic center from December 2010 to December 2014, with mean follow-up of 38 mo (range 12-169). Patients included had benign ureteroileal strictures longer than 1cm., Surgical Procedure: A pure laparoscopic approach was systematically used, involving a two-step procedure for left and a one-step procedure for right ureteral stenosis., Measurements: Perioperative data were collected and complications were assessed using the Clavien-Dindo grading system. Outcomes and follow-up data were analyzed., Results and Limitations: A descriptive statistical analysis was performed for 11 surgeries in ten patients. The median stricture length was 2.4cm. No conversion to open surgery was required. The mean blood loss was 180ml and the mean hospital stay was 10 d. Early complications included limited lymphorrhea (n=1), limited anastomotic leakage (n=2), and accidental descent of a ureteral catheter (n=1) that was replaced with radiologic intervention. The mean follow-up was 38 mo (range 12-169). No late complications were reported. After 1 yr of follow-up, six patients had good glomerular filtration rates, all patients were asymptomatic, and no stenotic relapses were detected., Conclusions: This laparoscopic technique for the management of benign secondary UAS is feasible, with good results and without long-term complications. This minimally invasive approach reduces the morbidity associated with open surgery while retaining good success rates., Patient Summary: We describe a novel laparoscopic approach for patients with a ureteroileal anastomosis stricture after radical cystectomy to avoid the complications associated with open surgery. The surgery was found to be viable and safe with good long-term results., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)

Purpose: Accurate noninvasive assessment of vertebral bone marrow fat fraction is important for diagnostic assessment of a variety of disorders and therapies known to affect marrow composition. Moreover, it provides a means to correct fat-induced bias of single energy quantitative computed tomography (QCT) based bone mineral density (BMD) measurements. The authors developed new segmentation and calibration methods to obtain quantitative surrogate measures of marrow-fat density in the axial skeleton., Methods: The authors developed and tested two high resolution-QCT (HR-QCT) based methods which permit segmentation of bone voids in between trabeculae hypothesizing that they are representative of bone marrow space. The methods permit calculation of marrow content in units of mineral equivalent marrow density (MeMD). The first method is based on global thresholding and peeling (GTP) to define a volume of interest away from the transition between trabecular bone and marrow. The second method, morphological filtering (MF), uses spherical elements of different radii (0.1-1.2 mm) and automatically places them in between trabeculae to identify regions with large trabecular interspace, the bone-void space. To determine their performance, data were compared ex vivo to high-resolution peripheral CT (HR-pQCT) images as the gold-standard. The performance of the methods was tested on a set of excised human vertebrae with intact bone marrow tissue representative of an elderly population with low BMD., Results: 86% (GTP) and 87% (MF) of the voxels identified as true marrow space on HR-pQCT images were correctly identified on HR-QCT images and thus these volumes of interest can be considered to be representative of true marrow space. Within this volume, MeMD was estimated with residual errors of 4.8 mg/cm(3) corresponding to accuracy errors in fat fraction on the order of 5% both for GTP and MF methods., Conclusions: The GTP and MF methods on HR-QCT images permit noninvasive localization and densitometric assessment of marrow fat with residual accuracy errors sufficient to study disorders and therapies known to affect bone marrow composition. Additionally, the methods can be used to correct BMD for fat induced bias. Application and testing in vivo and in longitudinal studies are warranted to determine the clinical performance and value of these methods.

This study explores potential signals of microdifferentiation in the gene pool of three high-altitude populations from Jujuy province in northwest Argentina using highly polymorphic markers. These human communities are characterized by extreme living conditions and very low population densities owing to considerable height above sea level and steep orography. A set of autosomal short tandem repeats (STRs) located at chromosome 6 (6p21.3) was typed in samples from Quebrada Baja (∼2,500 m), Quebrada Alta (∼3,300 m), and Puna (> 3,500 m). Genetic diversity was estimated through the observed and expected heterozygosities and the haplotype diversity. Analyses of the molecular variance (AMOVAs) and population differentiation tests based on allele and haplotype frequencies were performed to assess genetic heterogeneity among subgroups. No deviation from Hardy-Weinberg equilibrium was detected in any subpopulation, yet significant departures were detected in the analysis considering the whole area (D6S2792 and D6S105 loci). Overall, genetic diversity showed a decreasing trend as the altitude increased. Thus, allele and haplotype frequencies showed the most significant differences between Puna and Quebrada Baja, the populations sited at the edges of the altitude range. The trend toward reduction of heterozygosity with altitude is compatible with historical patterns of colonization, interregional migration trends, population density, and genetic admixture. The main consequence of the complex mountainous landscape of Jujuy would be an imbalance in the interplay of gene flow and genetic drift, favoring the latter. The combined effect of restricted gene flow and intense genetic drift would have promoted local genetic differentiation between the Jujuy highland subpopulations, leading to spatial patterning of the allele frequencies not entirely attributable to geographic distance. Our findings corroborate the effectiveness of STRs to identify microevolutionary changes.

Objective: To investigate the role of contemporary minilaparoscopy (ML; 3 mm instruments and laparoscope) and to identify predictive factors for complications in a prospective multicenter series for renal and adrenal surgeries., Materials and Methods: From July 2013 to December 2014, 110 patients from 6 laparoscopic Spanish centers were enrolled. A common database was used and data were collected in a prospective manner. Standard approach was defined as 3 to 4 3-mm trocars with a 3-mm laparoscope and 3-mm instruments (Karl Storz, Tuttlingen, Germany). Descriptive variables were analyzed and statistical analysis was performed for predictive factors for complications., Results: Patient mean age was 57.8 ± 14.6 years, with an average body mass index of 25.3 ± 3.6 kg/m(2). Median American Society of Anesthesiologists score was II and 32% (n = 35) of the patients had a previous surgery. A total of 59 nephrectomies, 20 partial nephrectomies, 9 nephroureterectomies, 13 pyeloplasties, 3 pyelolithotomies, and 6 adrenalectomies were performed. Overall operative time was 180 ± 64 minutes. There were 12 clampless partials and 8 with a mean warm ischemia time of 14 ± 7 min. There were 5% of intraoperative and 8% of postoperative complications (Clavien II-IV). Mean hospital stay was 5 ± 2.3 days, with optimal pain and cosmetic control., Conclusion: To our knowledge, this is one of the largest prospective series of ML for renal and adrenal surgeries. Despite a mean operative time possibly longer than in standard laparoscopy, clinical and safety outcomes are not compromised. Furthermore, ML results in excellent pain control and cosmetic outcomes., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Type 2 diabetes mellitus increases skeletal fragility; however, the contributing mechanisms and the efficacy of bone-forming agents are unclear. We studied diabetes and parathyroid hormone (PTH) treatment effects on cortical porosity (Ct.Po), non-enzymatic glycation (NEG) and bone mechanics in Zucker diabetic fatty (ZDF) rats. Eleven-week old ZDF diabetic (DB) and non-diabetic (ND) rats were given 75μg/kg PTH (1-84) or vehicle 5days per week over 12weeks. The right femora and L4 vertebrae were excised, micro-CT scanned, and tested in 3-point bending and uniaxial compression, respectively. NEG of the samples was determined using fluorescence. Diabetes increased Ct.Po (vertebra (vert): +40.6%, femur (fem): +15.5% vs. ND group, p<0.05) but had no effect on NEG. PTH therapy reduced vertebral NEG in the ND animals only (-73% vs untreated group, p<0.05), and increased femoral NEG in the DB vs. ND groups (+63%, p<0.05). PTH therapy had no effect on Ct.Po. Diabetes negatively affected bone tissue mechanics where reductions in vertebral maximum strain (-22%) and toughness (-42%) were observed in the DB vs. ND group (p<0.05). PTH improved maximum strain in the vertebra of the ND animals (+21%, p<0.05) but did not have an effect in the DB group. PTH increased femoral maximum strain (+21%) and toughness (+28%) in ND and decreased femoral maximum stress (-13%) and toughness (-27%) in the DB animals (treated vs. untreated, p<0.05). Ct.Po correlated negatively with maximum stress (fem: R=-0.35, p<0.05, vert: R=-0.57, p<0.01), maximum strain (fem: R=-0.35, p<0.05, vert: R=-0.43, p<0.05) and toughness (fem: R=-0.34, p<0.05, vert: R=-0.55, p<0.01), and NEG correlated negatively with toughness at the femur (R=-0.34, p<0.05) and maximum strain at the vertebra (R=-0.49, p<0.05). Diabetes increased cortical porosity and reduced bone mechanics, which were not improved with PTH treatment. PTH therapy alone may worsen diabetic bone mechanics through formation of new bone with high AGEs cross-linking. Optimal treatment regimens must address both improvements of bone mass and glycemic control in order to successfully reduce diabetic bone fragility. This article is part of a Special Issue entitled "Bone and diabetes"., (Copyright © 2015 Elsevier Inc. All rights reserved.)

In this paper, we report the synthesis of polycaprolactone (PCL) based hybrid materials containing hydrophilic domains composed of N-vinylpyrrolidone (VP), and γ-methacryloxypropyltrimethoxysilane (MPS). The hybrid materials were obtained by RAFT copolymerization of N-vinylpyrrolidone and MPS using a pre-formed dixanthate-end-functionalized PCL as macro-chain transfer agent, followed by a post-reaction crosslinking step. The composition of the samples was determined by elemental and thermogravimetric analyses. Differential scanning calorimetry and X-ray diffraction indicated that the crystallinity of PCL decreases in the presence of the hydrophilic domains. Scanning electron microscopy images revealed that the samples present an interconnected porous structure on the swelling. Compared to PCL, the hybrid materials presented low water contact angle values and higher elastic modulus. These materials showed controlled release of diclofenac, and biocompatibility with human periodontal ligament fibroblasts., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: The guidelines recommend partial surgery for T1 renal tumours. Various aspects of this surgery have evolved in recent years, including the clamping method and duration, enucleation, the retroperitoneoscopic approach and the use of 3mm ports. We present our initial series on laparoscopic renal tumourectomy by retroperitoneoscopy (LRTR) and analyse our learning curve and use of 3-mm instrumentation., Material and Methods: From January 2011 to January 2015, we performed LRTR on 50 patients with posterior or convex T1 renal tumours. After 10 cases, the technique changed to off-clamp, and 11 cases were subsequently performed with 3mm instrumentation., Results: The mean tumour size was 34.36 mm (14-62), with a mean PADUA score of 8.42 (5-12). The mean operative time was 163.1 minutes (75-300), and the mean warm ischaemia time was 4.21 minutes (0-28). The main renal artery was not clamped in 41 (82%) patients, and no vessel (zero ischaemia) was clamped in 39 (78%) patients. Seven cases had positive margins (6 focal). Eleven LRTRs were performed with 3mm instrumentation, with shorter surgical times, less intraoperative bleeding and shorter hospital stays., Conclusions: Retroperitoneoscopy coupled with enucleation enables the extirpation without clamping of posterior renal tumours, with a relatively short learning curve. The 3-mm material enables the technique to be performed, although in our experience it has resulted in a higher rate of positive surgical margins., (Copyright © 2015 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: The increase in recreational scuba diving in recent years, including children, involves risks and the possibility of accidents. While legislation, conditions and risks of scuba diving are well documented in adults, scientific evidence in scuba diving by children and adolescents is sparse and isolated. Furthermore, existing guidelines and recommendations for adults cannot be transferred directly to children., Methods: These circumstances have led to the Group on Techniques of the Spanish Society of Pediatric Pulmonology (SENP) to perform a literature search to review and update the knowledge about scuba diving in children., Results: Physiological adaptations of the body are examined during the dive, as well as the anatomical and physiological characteristics of children that should be taken into account in scuba diving. The most common types of accidents and its causes, as well as the risks of scuba diving practice in children with previous diseases are discussed, along with details of the medical and psychological requirements for scuba diving to be considered in the assessment of child and adolescent., Conclusions: A list of recommendations for scuba diving with compressed air in children is presented by a group of experts., (Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.)

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., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

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.

Purpose: To describe the prevalence of malformations found in fetuses with trisomy of chromosomes 13, 18 and 21 by identifying the most frequent within each condition., Methods: A retrospective cross-sectional study with the analysis of trisomy cases of chromosomes 13, 18 and 21 diagnosed through fetal karyotype obtained by amniocentesis/cordocentesis, between October 1994 and May 2014, at a Teaching Hospital in Brazil Southern Region. Malformations identified through morphological ultrasonography were described and, subsequently, confirmed in newborn examinations and/or fetal autopsy. The results were analyzed using Fisher's test and analysis of variance (ANOVA), with a 5% level of significance (p=0.05)., Results: Sixty-nine cases of trisomy were diagnosed among 840 exams; nine were excluded due to outcome outside Hospital de Clínicas de Porto Alegre or incomplete records, remaining 60 cases (nine cases of chromosome 13 trisomy, 26 of chromosome 18, and 25 of chromosome 21). In all three groups, heart disease occurred in most cases; the ventricular septal defect was more prevalent and occurred in 66.7% of the trisomy 13 group. Gastrointestinal abnormalities were more prevalent in the trisomy 18 group, especially omphalocele (38.5%; p<0.01). Genitourinary anomalies were more significantly frequent in the trisomy 13 group (pyelectasis, 55.6% - p<0.01; ambiguous genitalia, 33.3% - p=0.01). Central nervous system defects were identified in all cases of trisomy 13. Facial cracks were significantly more prevalent among fetuses with trisomy 13 (66.7%; p<0.01). Hand and feet malformations significantly differed among the trisomy groups. Hand defects occurred in 50% of trisomy 18 cases, and in 44.4% of all trisomy 13 cases (p<0.01); congenital clubfoot was more common in the trisomy 18 group, being detected in 46.2% of fetuses (p<0.01). The abnormalities were found in 50.9, 27.3 and 21.7% of trisomy 18, 13 and 21 cases respectively., Conclusion: Many fetal malformations identified at ultrasound are suggestive of trisomy and represent an important tool for etiologic diagnosis and prenatal and pre-conception genetic counseling.

Objectives: Rescue lymphadenectomy for testicular cancer is a complex surgery, with a high number of complications. The laparoscopic approach appears to offer faster recovery and improved quality of life compared with open surgery. The aim of our study is to report on our experience and to define whether there is a limit (oncological, anatomical or technical) for laparoscopic management., Material and Methods: A retrospective study was conducted of 15 patients who underwent laparoscopic retroperitoneal lymphadenectomy after chemotherapy. In addition to epidemiological and oncologic variables, we analyzed the mean surgical time, intraoperative and postoperative complications, the mean hospital stay and the mean follow-up time., Results: The mean surgical time was 294 minutes (range, 180-240). There were 4 large-vessel vascular lesions, all of which were large-volume retroperitoneal masses, with diameters >7 cm. The rate of postoperative complications was 33%; there was only 1 case of Clavien >III. The mean hospital stay was 5.38 days (range, 2-9), and the mean patient follow-up was 28.9 months (range, 1-79). There was no recurrence in any of the cases., Conclusions: The laparoscopic approach is an oncologically safe option for the rescue treatment of testicular cancer. The complex location of these masses entails the onset of severe intraoperative complications. We have observed a clear relationship between vascular complications and large masses (>7 cm). We therefore believe that it would be appropriate to establish a limit on the size for laparoscopic treatment., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

Introduction: Chronic hepatitis B virus (HBV) infection is an increasing cause of morbidity and mortality in human immunodeficiency virus (HIV)-infected individuals. HIV-positive patients are commonly co-infected with HBV due to shared routes of transmission., Objectives: Our aim was to determine the risk factors, prevalence, genotypes, and mutations of the Surface S gene of HBV, and occult hepatitis B infection (OBI) among patients infected with HIV in a northeastern Colombian city., Methods: A cross-sectional study was conducted with 275 HIV-positive patients attending an outpatient clinic in Bucaramanga, Colombia during 2009-2010. Blood samples were collected and screened for serological markers of HBV (anti-HBs, anti-HBc and HBsAg) through ELISA assay. Regardless of their serological profile, all samples were tested for the HBV S gene by nested-PCR and HBV genotypes were determined by phylogenetic inference. Clinical records were used to examine demographic, clinical, virological, immunological and antiretroviral therapy (ART) variables of HIV infection., Results: Participants were on average 37±11 years old and 65.1% male. The prevalence of HIV-HBV coinfection was 12% (95%CI 8.4-16.4) of which 3.3% had active HBV infection and 8.7% OBI. The prevalence of HIV-HBV coinfection was associated with AIDS stage and ART treatment. Sequence analysis identified genotype F, subgenotype F3 in 93.8% of patients and genotype A in 6.2% of patients. A C149R mutation, which may have resulted from failure in HBsAg detection, was found in one patient with OBI., Conclusions: The present study found a high prevalence of HIV-HBV coinfection with an incidence of OBI 2.6-fold higher compared to active HBV infection. These findings suggest including HBV DNA testing to detect OBI in addition to screening for HBV serological markers in HIV patients.

The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ~10,000 years before present (YBP), with signals of expansions at ~3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈ 15%) of the Franco-Cantabrian maternal gene pool with a putative pre-Neolithic origin to ≈ 35%, further supporting the notion of a predominant Paleolithic genetic substrate in extant European populations.

Purpose: To evaluate our initial outcomes of retroperitoneal partial nephrectomy (RPN) performed by off-clamp excision., Patients and Methods: Between January 2011 and October 2102, patients with T1 posterior renal masses or in the renal convexity were selected for RPN with the intent of performing the modified zero ischemia technique. Patient characteristics, operative details, complications, and long-term outcomes were analyzed., Results: There were 19 patients included (mean age 60 years, range 37-81 years; body mass index 27.8 kg/m(2), range 25-34 kg/m(2)). Mean tumor size was 35 mm (20-50 mm), and preoperative aspects and dimensions used for an anatomical (PADUA) classification score was 9 (7-11). Surgical time was 182 minutes (110-255 min), and the series warm ischemia time was 4.9 minutes (0-28 min). The off-clamp procedure was performed in 15 (79%) patients. Mean estimated blood losses (EBL) were 414 mL (100-1600 mL). Transfusion was necessary in two cases, while one reoperation and one conversion to open surgery were needed. Mean hospital stay was 4.5 days (range 3-11). One (5.3%) case of positive margins was reported. Serum creatinine levels varied from 86 to 94 μmol/L (preoperative and 6-month follow-up). Considering the learning curve of the technique, separate analysis of the initial 9 and last 10 cases revealed that while tumor characteristics remained comparable (size 33 vs 37 mm; PADUA score 8.8 vs 9.2), no clamping was performed in the later cases with decreased EBL (544 vs 297 mL), surgical time (207 vs 159 min), and shorter hospital stay (5 vs 4 days)., Conclusion: Our preliminary results on off-clamp RPN are promising and may pave the way for a real zero ischemia nephron-sparing surgery. Larger and randomized studies should follow in to confirm our initial results.