A Cadaver-based Comparison of Sleeve-guided Implant-drill and Dynamic Navigation Osteotomy and Root-end Resections.

INTRODUCTION: This study compared the accuracy and efficiency of fully guided static and dynamic computer-assisted surgical navigation techniques for osteotomy and root-end resection (RER). METHODS: Fifty roots from cadaver heads were divided into two groups: fully guided static computer-assisted endodontic microsurgery (FG sCAEMS) and dynamic computer-assisted endodontic microsurgery (dCAEMS) (all, n = 25). Cone-beam computed tomography scans were taken pre and postoperatively. The osteotomy and RER were planned virtually in the preoperative cone-beam computed tomography scan and guided using 3D-printed surgical guides in the FG sCAEMS and 3D-dynamic navigation system in the dCAEMS. The 2D and 3D deviations and angular deflection were calculated. The osteotomy volume, resected root length, and resection angle were measured. The osteotomy and RER time and the number of procedural mishaps were recorded. RESULTS: FG sCAEMS was as accurate as dCAEMS, with no difference in the 2D and 3D deviation values or angular deflection (P > .05). The osteotomy and RER time were shortened using FG sCAEMS (P < .05). The FG sCAEMS showed a greater number of incomplete RERs than dCAEMS. Osteotomy volume, RER angle, and root length resected were similar in both groups (P > .05). FG sCAEMS and dCAEMS were feasible for osteotomy and RER. CONCLUSIONS: Within the limitations of this cadaver-based study, FG sCAEMS was as accurate as dCAEMS. Both FG sCAEMS and dCAEMS were time-efficient for osteotomy and RER.

Comparison of a Novel Static Computer-aided Surgical and Freehand Techniques for Osteotomy and Root-end Resection.

INTRODUCTION: This study compared the accuracy and efficiency of a novel static computer-aided surgical technique using a 3-dimensional (3D)-printed surgical guide (3D-SG) with a fully guided drill protocol (3D-SG FG) to the freehand (FH) osteotomy and root-end resection (RER). METHODS: Forty-six roots from 2 cadaver heads were divided into 2 groups: 3D-SG FG (n = 23) and FH (n = 23). Cone-beam computed tomographic scans were taken preoperatively and postoperatively. The endodontic microsurgery was planned in Blue Sky Bio software, and the 3D-SG was designed and 3D printed. The osteotomy and RER were conducted using a guided twist drill diameter of 2 mm and an ascending tapered drill with diameters of 2.8/3.2, 3.2/3.6, 3.8/4.2, and 4.2 mm with respective guided drill guides. Two-dimensional and three-dimensional virtual deviations and angular deflection were calculated. Linear osteotomy measures and root resection angle were obtained. The osteotomy and RER time and the number of mishaps were recorded. RESULTS: Two-dimensional and three-dimensional accuracy deviations and angular deflection were lower in the 3D-SG FG protocol than in the FH technique (P < .05). The height, length, and depth of the osteotomy and root resection angle were less in the 3D-SG FG protocol than in the FH technique (P < .05). The osteotomy and RER time with the 3D-SG FG protocol were less than the FH method (P < .05). CONCLUSIONS: Within the limitations of this cadaver-based study using denuded maxillary and mandibular jaws, 3D-SG FG protocol showed higher accuracy than FH osteotomy and RER. Moreover, the 3D-SG FG drill protocol significantly reduced the surgical time.

Toxoplasma gondii seropositivity associated to peri-urban living places in pregnant women in a rural area of Buenos Aires province, Argentina.

Infection with Toxoplasma gondii is very common in humans throughout the world, the intake of raw or undercooked meat with tissue cysts and fruits, vegetables and water contaminated with parasite oocysts being the main routes of infection. Here, we analyzed the seroprevalence of anti-T. gondii antibodies in pregnant females (age 13-44 years; n = 920) between April 2014 and December 2017 from Chascomús (Argentina), a city immersed in a rural area. Altogether 320 tested positive for immunoglobulin G antibodies, yielding an overall seroprevalence of 34.8% (CI 95%: 31.7-37.9). No association was observed between seropositivity and age. In addition, by using the QGIS 3.2.1 software we analyzed the geographical distribution of 769 (83.6%) pregnant females in two main areas of the city: Urban (n = 157) and Peri-urban (n = 612) with a seroprevalence of 26.8% (CI 95%: 19.8-33.7) and 36.4% (CI 95%: 32.6-40.3) respectively, and this difference was statistically significant (p = 0.023). Furthermore, we assessed through a questionnaire survey, between April 2016 to December 2017, possible risk factors such as activity (urban and rural), home water supply, animal husbandry, presence of cats as pets, gardening and consumption of meat and its derivatives (pork, sheep meat and sausages) and their frequencies (consumption per week), not finding significant association with seropositivity. Significant differences was found when the seroprevalence was analyzed between the urban and peri-urban neighborhoods of the city of Chascomús. The higher seroprevalence in peri-urban neighborhoods could be due to an unfavorable socioeconomic situation and/or to undeveloped peri-urban environments, which is a risk factor that should be taken into account when planning the health care of pregnant females.

Selected renal cells modulate disease progression in rodent models of chronic kidney disease via NF-κB and TGF-ß1 pathways.

AIM: Identification of mechanistic pathways for selected renal cell (SRC) therapeutic bioactivity in rodent models of chronic kidney disease. MATERIALS & METHODS: In vivo and in vitro functional bioassays applied to investigate regenerative outcomes associated with delivery of SRC to diseased rodent kidney. RESULTS: In vivo, SRC reduces chronic infiltration by monocytes/macrophages. SRC attenuates NF-κB and PAI-1 responses while simultaneously promoting host tubular cell expansion through trophic cues. In vitro, SRC-derived conditioned media attenuates TNF-α-induced NF-κB response, TGF-ß-mediated PAI-1 response and increases expression of transcripts associated with cell cycle regulation. Observed bioactive responses were from vesicle and nonvesicle-associated factors, including specific miRNAs. CONCLUSION: We identify a paracrine mechanism for SRC immunomodulatory and trophic cues on host renal tissues, catalyzing long-term functional benefits in vivo.

Calidad de la ejecución del subprograma de atención comunitaria al adulto mayor del Policlínico Universitario "José Martí" / Quality of implementation of the community care subprogram for older adult at "José Martí" University Polyclinic

Se realizó una investigación en sistemas y servicios de salud para evaluar la calidad de la ejecución del Subprograma de Atención Comunitaria al Adulto Mayor en el área de salud correspondiente al Policlínico Universitario "José Martí Pérez" de Santiago de Cuba, desde noviembre del 2010 hasta igual mes del 2011. El universo estuvo constituido por 72 profesionales y 63 ancianos frágiles del área antes citada. Se evaluaron los elementos estructura (recursos humanos, materiales), proceso (competencia profesional) y resultados (satisfacción de los proveedores y usuarios e indicadores del programa). La calidad de la ejecución del subprograma fue inadecuada, debido a la insuficiente competencia e insatisfacción de los profesionales de la salud evaluados, por lo cual se evidenciaron dificultades tanto en el proceso como en los resultados. Por tales razones se recomendó efectuar un estudio de intervención relacionado con las deficiencias encontradas en la evaluación de la calidad de la ejecución del subprograma.

A research in health systems and services was made to assess the quality of implementation of the Community Care Subprogram for Older Adult in the health area corresponding to "José Martí Pérez" University Polyclinic of Santiago de Cuba, from November 2010 to the same month of 2011. The sample was formed by 72 professionals and 63 fragile elderly of that area. Elements such as structure (human resources, material), process (professional competence) and outcomes (satisfaction of users and providers and program indicators) were assessed. Implementation quality of the subprogram was inadequate due to insufficient competence and dissatisfaction of health professionals evaluated, thus difficulties were evident in both the process and the outcomes. For these reasons it was recommended to make an intervention study related to the deficiencies in the quality assessment of the subprogram implementation.

Fabrication of a multi-layer three-dimensional scaffold with controlled porous micro-architecture for application in small intestine tissue engineering.

Various methods can be employed to fabricate scaffolds with characteristics that promote cell-to-material interaction. This report examines the use of a novel technique combining compression molding with particulate leaching to create a unique multi-layered scaffold with differential porosities and pore sizes that provides a high level of control to influence cell behavior. These cell behavioral responses were primarily characterized by bridging and penetration of two cell types (epithelial and smooth muscle cells) on the scaffold in vitro. Larger pore sizes corresponded to an increase in pore penetration, and a decrease in pore bridging. In addition, smaller cells (epithelial) penetrated further into the scaffold than larger cells (smooth muscle cells). In vivo evaluation of a multi-layered scaffold was well tolerated for 75 d in a rodent model. This data shows the ability of the components of multi-layered scaffolds to influence cell behavior, and demonstrates the potential for these scaffolds to promote desired tissue outcomes in vivo.

A population of selected renal cells augments renal function and extends survival in the ZSF1 model of progressive diabetic nephropathy.

New treatment paradigms that slow or reverse progression of chronic kidney disease (CKD) are needed to relieve significant patient and healthcare burdens. We have shown that a population of selected renal cells (SRCs) stabilized disease progression in a mass reduction model of CKD. Here, we further define the cellular composition of SRCs and apply this novel therapeutic approach to the ZSF1 rat, a model of severe progressive nephropathy secondary to diabetes, obesity, dyslipidemia, and hypertension. Injection of syngeneic SRCs into the ZSF1 renal cortex elicited a regenerative response that significantly improved survival and stabilized disease progression to renal structure and function beyond 1 year posttreatment. Functional improvements included normalization of multiple nephron structures and functions including glomerular filtration, tubular protein handling, electrolyte balance, and the ability to concentrate urine. Improvements to blood pressure, including reduced levels of circulating renin, were also observed. These functional improvements following SRC treatment were accompanied by significant reductions in glomerular sclerosis, tubular degeneration, and interstitial inflammation and fibrosis. Collectively, these data support the utility of a novel renal cell-based approach for slowing renal disease progression associated with diabetic nephropathy in the setting of metabolic syndrome, one of the most common causes of end-stage renal disease.

Regeneration of native-like neo-urinary tissue from nonbladder cell sources.

Urinary pathology requiring urinary diversion, partial or full bladder replacement, is a significant clinical problem affecting ~14,000 individuals annually in the United States alone. The use of gastrointestinal tissue for urinary diversion or bladder reconstruction/replacement surgeries is frequently associated with complications. To try and alleviate or reduce the frequency of these complications, tissue engineering and regenerative medicine strategies have been developed using bio-absorbable materials seeded with cells derived from the bladder. However, bladder-sourced cells may not always be suitable for such applications, especially in patients with bladder cancer. In this study, we describe the isolation and characterization of smooth muscle cells (SMCs) from porcine adipose and peripheral blood that are phenotypically and functionally indistinguishable from bladder-derived SMCs. In a preclinical Good Laboratory Practice study, we demonstrate that autologous adipose- and peripheral blood-derived SMCs may be used to seed synthetic, biodegradable tubular scaffold structures and that implantation of these seeded scaffolds into a porcine cystectomy model leads to successful de novo regeneration of a tubular neo-organ composed of urinary-like neo-tissue that is histologically identical to native bladder. The ability to create urologic structures de novo from scaffolds seeded by autologous adipose- or peripheral blood-derived SMCs will greatly facilitate the translation of urologic tissue engineering technologies into clinical practice.

Isolation, characterization, and expansion methods for defined primary renal cell populations from rodent, canine, and human normal and diseased kidneys.

Chronic kidney disease (CKD) is a global health problem; the growing gap between the number of patients awaiting transplant and organs actually transplanted highlights the need for new treatments to restore renal function. Regenerative medicine is a promising approach from which treatments for organ-level disorders (e.g., neurogenic bladder) have emerged and translated to clinics. Regenerative templates, composed of biodegradable material and autologous cells, isolated and expanded ex vivo, stimulate native-like organ tissue regeneration after implantation. A critical step for extending this strategy from bladder to kidney is the ability to isolate, characterize, and expand functional renal cells with therapeutic potential from diseased tissue. In this study, we developed methods that yield distinct subpopulations of primary kidney cells that are compatible with process development and scale-up. These methods were translated to rodent, large mammal, and human kidneys, and then to rodent and human tissues with advanced CKD. Comparative in vitro studies demonstrated that phenotype and key functional attributes were retained consistently in ex vivo cultures regardless of species or disease state, suggesting that autologous sourcing of cells that contribute to in situ kidney regeneration after injury is feasible, even with biopsies from patients with advanced CKD.

A novel bioengineered small-caliber vascular graft incorporating heparin and sirolimus: excellent 6-month patency.

OBJECTIVE: A bioengineered microporous polycarbonate-siloxane polyurethane graft has been developed for coronary artery bypass grafting. Biological agents can be impregnated into its absorbable collagen and hyaluronan microstructure and stable macrostructure to promote patency. The objective of this study was to examine the in vivo biological performance and biomechanical characteristics of this graft. METHODS: Three types of graft (3.6-mm internal diameter, 24-mm length) were manufactured: heparin alone (H) grafts, heparin and sirolimus (HS) grafts, and grafts without any drug impregnation (C). All H and HS grafts were impregnated with 54 U of heparin in the microstructure for early elution to prevent acute graft thrombosis and 56 U of heparin in the macrostructure to prevent late thrombosis. In addition to the heparin, the HS graft was impregnated with 2.1 mg of sirolimus in the macrostructure for prolonged elution to inhibit intimal hyperplasia. All grafts (3.6-mm internal diameter, 24-mm length) were implanted into the abdominal aortas of rabbits (n = 55). Expanded polytetrafluoroethylene grafts (4.0-mm internal diameter, 24-mm length; n = 7) were implanted as controls. At 1, 3, and 6 months after surgery, the grafts were removed for histologic, scanning electron microscopic, immunohistochemical, and biomechanical evaluations. RESULTS: The patency rate was 100% in the H, HS, and C grafts at each time point. Although the expanded polytetrafluoroethylene grafts were patent at 1 and 3 months after surgery, 1 of 2 grafts (50%) were occluded at 6 months. None of the H or HS grafts had any stenosis or thrombus. Scanning electron microscopic examination proved that endothelial cells propagated smoothly from the anastomotic sites after 6 months in the H and HS grafts in comparison with the expanded polytetrafluoroethylene grafts, which had rare endothelialization. Neointima formation was inhibited in the HS graft compared with the H or C graft at 6 months (123 +/- 126 microm vs 206 +/- 158 microm or 202 +/- 67 microm; P < .05). In addition, the H, HS, and C grafts had greater cellular infiltration inside the graft than the expanded polytetrafluoroethylene grafts. All grafts except the expanded polytetrafluoroethylene graft had marked neocapillary formation 6 months after surgery. The graft compliance between 80 and 120 mm Hg was 6.0% +/- 2.5% and 6.2% +/- 0.9% at 6 months in the H and HS grafts, respectively. The graft macrostructure was unchanged according to the biomechanical evaluation in the H and HS grafts. CONCLUSION: A unique drug-eluting graft had excellent patency throughout the 6 months after implantation. The heparin-sirolimus graft encouraged luminal endothelialization without excessive intimal hyperplasia. This graft performed significantly better than the expanded polytetrafluoroethylene graft. This graft has the potential to become an implantable graft for coronary artery bypass grafting.

Novel bioengineered small caliber vascular graft with excellent one-month patency.

BACKGROUND: A bioengineered microporous polycarbonate-siloxane polyurethane graft has been developed for coronary artery bypass grafting. Biological agents can be impregnated into its absorbable collagen and hyaluronan microstructure and stable macrostructure to promote patency. The objective of this study was to examine the biological performance and biomechanical characteristics of this graft. METHODS: Heparin-sirolimus (HS) or heparin-sirolimus-vascular endothelial growth factor (HSV) grafts were manufactured for this study. Heparin (40 U) was embedded in the microstructure of the graft for early elution from the graft wall. Heparin (100 U) and sirolimus (450 microg) were incorporated into the macrostructure of the graft for late elution. Vascular endothelial growth factor was also embedded in the microstructure of the graft. Both grafts (3.6 mm internal diameter, 24 mm length) were implanted into the abdominal aortas of rabbits (n = 36) to compare with heparin-alone (H) grafts (n = 9). At 4 hours, 1 day, and 1, 2, and 4 weeks after surgery, the grafts were removed for histologic, immunohistochemical, and biomechanical evaluations. RESULTS: The patency rate of all grafts was 100% at each time point. None of grafts had stenosis after surgery. Endothelial cells were observed at 4 weeks after surgery in the HS, HSV, and H grafts. Although there was no significant difference of neointima thickness among the HS, HSV, and H grafts (136 +/- 75, 93 +/- 64, and 125 +/- 90 microm; p = 0.08), the H grafts did have more cellular infiltration in the graft than the HS or HSV grafts. There was neocapillary formation inside the graft wall at 4 weeks in all grafts. The graft macrostructure was unchanged based on biomechanical evaluation 4 weeks after surgery. CONCLUSIONS: A unique drug-eluting graft had excellent patency at 1 month and may encourage luminal endothelialization without excessive intimal hyperplasia. Although vascular endothelial growth factor did not improve intimal formation, cell infiltration, or vascularization, sirolimus might inhibit cell proliferation. Further long-term study would need to evaluate the efficacy of impregnated sirolimus.

Evaluation of a novel endoluminal vascular occlusion device in a porcine model: early and late follow-up.

PURPOSE: To evaluate the efficacy of a new vascular occlusion device (VOD) in a preclinical controlled study versus embolization coils. METHODS: The Biomerix VOD was made from a biodurable porous polyurethane matrix in the shape of a cylinder measuring 1.5 cm long by 6.0 mm wide. Thirty-three swine were selected to undergo embolization of a 3 to 5-mm-diameter iliac artery using either a single VOD (27 animals) or sufficient Cook fibered stainless steel coils to achieve angiographic occlusion (6 controls). Test animals were assigned to undergo angiography at 1 week (n=11), 1 month (n=6), 3 months (n=6), or 6 months (n=4). Two control animals were assigned to angiographic follow-up at 1 week, 1 month, and 3 months. Test and control animals were euthanized at each time point to explant occluded vessels for histological analysis. Study endpoints were device utilization, time to occlusion, postdeployment migration, and persistent angiographic occlusion at 7, 30, 90, and 180 days. RESULTS: One VOD was deployed in each test animal, whereas a mean 3.3+/-0.8 coils were needed to achieve angiographic occlusion in the 6 controls (p<0.001). The time to occlusion was significantly shorter with the VOD (1.46+/-0.73 versus 5.83+/-1.60 minutes for the coils; p<0.001). There was no evidence of recanalization or filling defects at the site of VOD deployment, while filling defects were seen in 3 of 6 coil-treated controls. The VOD arm showed superior angiographic occlusion versus coils at the 1-week, 1-month, and 3-month angiographic follow-up time points. Histological evaluation showed that the VOD was equivalent to the embolization coils at the 1-week (n=6) and 1-month (n=6) endpoint (100% luminal occlusion). In the 3-month group (n=6), the VOD showed 95% to 100% luminal occlusion versus 90% to 95% in the control animals. In the 6-month group, VOD showed 85% to 95% occlusion. CONCLUSIONS: The Biomerix VOD appears highly effective and reliable, resulting in significantly faster and longer lasting occlusion compared with fibered stainless steel embolization coils.

Transepicardial autologous bone marrow-derived mononuclear cell therapy in a porcine model of chronically infarcted myocardium.

OBJECTIVE: Cell therapy is becoming a viable strategy to improve revascularization and myocardial function after myocardial injury. We evaluated the effect of bone marrow-derived mononuclear cell (BMMNC) transplantation on collateral vessel development and myocardial function in a porcine model of chronically infarcted heart. METHODS: Myocardial infarction was produced in 13 domestic swine. At 4 weeks, animals were randomized to receive transepicardial injections of autologous BMMNCs (approximately 24x10(6) cells, n=8) or phosphate buffered saline (PBS; control, n=5) into infarcted and border regions. Collateral growth, angiogenesis, and infarct size were assessed by angiography, immunohistochemistry, and histomorphometry. RESULTS: Regional contractility was assessed by transepicardial echocardiography at baseline and 4 weeks following treatment. Angiography revealed a trend toward increased collateral growth in the BMMNC group. Wall motion score index (myocardial function) was similar in both groups at baseline (1.63+/-0.16 vs. 1.25+/-0.25, P=.21) and at 4 weeks (1.83+/-0.22 vs. 1.63+/-0.38, P=.62). alpha-Actin-positive smooth muscle cells (SMCs) and Factor VIII positive endothelial cells were significantly greater in the BMMNC-injected animals (314.8+/-37.4/0.1 vs. 167.1+/-11.9/0.1 mm(2) in controls, P=.02, and 363.3+/-28.2 cells/0.1 mm(2) vs. 254.4+/-28.1 cells/0.1 mm(2) in controls, P=.03, respectively). The number of blood vessels >50 mum in diameter was significantly increased in the BMMNC group (317.9+/-54.9 vs. 149.1+/-6.1, P<.05). The size of the infarct area was smaller in the BMMNC-transplanted group than in the controls (P=.015). CONCLUSION: BMMNC transplantation appears to improve angiogenesis and reduce infarct size yet results in no improvement in left ventricular function in a chronically infarcted heart.