Histological characterization of the human scapholunate ligament.

The scapholunate interosseous ligament (SLIL) plays a fundamental role in stabilizing the wrist bones, and its disruption is a frequent cause of wrist arthrosis and disfunction. Traditionally, this structure is considered to be a variety of fibrocartilaginous tissue and consists of three regions: dorsal, membranous and palmar. Despite its functional relevance, the exact composition of the human SLIL is not well understood. In the present work, we have analyzed the human SLIL and control tissues from the human hand using an array of histological, histochemical and immunohistochemical methods to characterize each region of this structure. Results reveal that the SLIL is heterogeneous, and each region can be subdivided in two zones that are histologically different to the other zones. Analysis of collagen and elastic fibers, and several proteoglycans, glycoproteins and glycosaminoglycans confirmed that the different regions can be subdivided in two zones that have their own structure and composition. In general, all parts of the SLIL resemble the histological structure of the control articular cartilage, especially the first part of the membranous region (zone M1). Cells showing a chondrocyte-like phenotype as determined by S100 were more abundant in M1, whereas the zone containing more CD73-positive stem cells was D2. These results confirm the heterogeneity of the human SLIL and could contribute to explain why certain zones of this structure are more prone to structural damage and why other zones have specific regeneration potential. RESEARCH HIGHLIGHTS: Application of an array of histological analysis methods allowed us to demonstrate that the human scapholunate ligament is heterogeneous and consists of at least six different regions sharing similarities with the human cartilage, ligament and other anatomical structures.

Extensor Pollicis Brevis Transosseous Tenodesis Technique for Treatment of Acquired Metacarpophalangeal Hyperextension Deformity of the Thumb: A Preliminary Report.

SUMMARY: Hyperextension deformity of the metacarpophalangeal joint of the thumb causes pain and loss of function. Although many treatments have been proposed, none of them are universally accepted as ideal. The authors report a study of 12 symptomatic hyperextension deformities of the thumb metacarpophalangeal joint in 10 patients who underwent surgical correction. The purpose of this study was to describe a new technique of tenodesis of the thumb metacarpophalangeal joint using the extensor pollicis brevis tendon. The technique consists of extensor pollicis brevis tenotomy at the wrist and tendon transfer through two bone tunnels to the palmar aspect of the metacarpophalangeal joint before metacarpal fixation with a flexor tenodesis effect. Correction of hyperextension and range of motion were assessed. Functional changes were evaluated by Quick Disabilities of the Arm, Shoulder, and Hand score, pain visual analogue scale, Kapandji opposition scheme, and pinch strength. The Wilcoxon test was used for statistical analysis. Mean preoperative and postoperative metacarpophalangeal joint hyperextension deformities were +50.83 ± 5.57 degrees and -17.91 ± 7.82 degrees, respectively. Thumb opposition improved by one point on Kapandji's scheme. Mean perceived pain decreased from 7.66 to 1.16. On average, the Quick Disabilities of the Arm, Shoulder, and Hand score was reduced by 34.4 points and pinch strength increased by 50.42 percent. The authors found that extensor pollicis brevis transosseous tenodesis is a safe and minimally invasive method for successfully correcting the functionality and cosmetic appearance of metacarpophalangeal joint hyperextension deformities in posttraumatic and trapeziometacarpal osteoarthritis cases. The patients retained functional active flexion, even in deformities greater than 40 degrees. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Improvement of Cell Culture Methods for the Successful Generation of Human Keratinocyte Primary Cell Cultures Using EGF-Loaded Nanostructured Lipid Carriers.

Human skin keratinocyte primary cultures can be established from skin biopsies with culture media containing epithelial growth factor (EGF). Although current methods are efficient, optimization is required to accelerate the procedure and obtain these cultures in less time. In the present study, we evaluated the effect of novel formulations based on EGF-loaded nanostructured lipid carriers (NLC). First, biosafety of NLC containing recombinant human EGF (NLC-rhEGF) was verified in immortalized skin keratinocytes and cornea epithelial cells, and in two epithelial cancer cell lines, by quantifying free DNA released to the culture medium. Then we established primary cell cultures of human skin keratinocytes with basal culture media (BM) and BM supplemented with NLC-rhEGF, liquid EGF (L-rhEGF), or NLC alone (NLC-blank). The results showed that cells isolated by enzymatic digestion and cultured with or without a feeder layer had a similar growth rate regardless of the medium used. However, the explant technique showed higher efficiency when NLC-rhEGF culture medium was used, compared to BM, L-rhEGF, or NLC-blank. Gene expression analysis showed that NLC-rhEGF was able to increase EGFR gene expression, along with that of other genes related to cytokeratins, cell-cell junctions, and keratinocyte maturation and differentiation. In summary, these results support the use of NLC-rhEGF to improve the efficiency of explant-based methods in the efficient generation of human keratinocyte primary cell cultures for tissue engineering use.

Biofabrication of a Tubular Model of Human Urothelial Mucosa Using Human Wharton Jelly Mesenchymal Stromal Cells.

Several models of bioartificial human urothelial mucosa (UM) have been described recently. In this study, we generated novel tubularized UM substitutes using alternative sources of cells. Nanostructured fibrin-agarose biomaterials containing fibroblasts isolated from the human ureter were used as stroma substitutes. Then, human Wharton jelly mesenchymal stromal cells (HWJSC) were used to generate an epithelial-like layer on top. Three differentiation media were used for 7 and 14 days. Results showed that the biofabrication methods used here succeeded in generating a tubular structure consisting of a stromal substitute with a stratified epithelial-like layer on top, especially using a medium containing epithelial growth and differentiation factors (EM), although differentiation was not complete. At the functional level, UM substitutes were able to synthesize collagen fibers, proteoglycans and glycosaminoglycans, although the levels of control UM were not reached ex vivo. Epithelial differentiation was partially achieved, especially with EM after 14 days of development, with expression of keratins 7, 8, and 13 and pancytokeratin, desmoplakin, tight-junction protein-1, and uroplakin 2, although at lower levels than controls. These results confirm the partial urothelial differentiative potential of HWJSC and suggest that the biofabrication methods explored here were able to generate a potential substitute of the human UM for future clinical use.

Biomechanical Finite Element Method Model of the Proximal Carpal Row and Experimental Validation.

The Finite Element Method (FEM) models are valuable tools to create an idea of the behavior of any structure. The complexity of the joints, materials, attachment areas, and boundary conditions is an open issue in biomechanics that needs to be addressed. Scapholunate instability is the leading cause of wrist pain and disability among patients of all ages. It is needed a better understanding of pathomechanics to develop new effective treatments. Previous models have emulated joints like the ankle or the knee but there are few about the wrist joint. The elaboration of realistic computational models of the carpus can give critical information to biomedical research and surgery to develop new surgical reconstructions. Hence, a 3D model of the proximal carpal row has been created through DICOM images, making a reduced wrist model. The materials, contacts, and ligaments definition were made via open-source software to extract results and carry on a reference comparison. Thus, considering the limitations that a reduced model could carry on (unbalanced forces and torques), the stresses that result in the scapholunate interosseous ligament (SLIL) lead us to a bones relative displacement, which support the kinematics hypothesis in the literature as the distal carpal row moves as a rigid solid with the capitate bone. Also, experimental testing is performed, successfully validating the linear strength values of the scapholunate ligament from the literature.

Modification of intra-carpal tunnel pressure after Z-lengthening of the transverse carpal ligament.

Background Flexor retinaculum reconstruction techniques or simply Flexor Retinaculum Z-lengthening have been proposed to preserve Flexor Retinaculum continuity after carpal tunnel release. Their effectiveness is based solely on symptom relief. There has been no analysis of the effects on intra-carpal tunnel pressure of Flexor Retinaculum-lengthening techniques. Objective was to compare intra-carpal tunnel pressure outcomes between complete division and Z-lengthening of the Retinaculum in a cadaveric model of carpal tunnel release. Methods Experimental study of carpal tunnel pressure after surgical Flexor Retinaculum modification in 10 fresh-frozen forearm and hand cadaveric specimens. The Kyphon™ Balloon Kyphoplasty system was used to measure the pressure before and after infusing 1, 2, 3, 4 and 5 ml of saline solution when untreated (Flexor Retinaculum continuity stage I), when Z-lengthened (Flexor Retinaculum continuity stage II), and after complete Flexor Retinaculum division (Flexor Retinaculum continuity stage III). Finding Intra-carpal tunnel pressure increased with larger volume of infused saline solution, although mean pressures were lower after Z lengthening or complete division of the Retinaculum than at baseline. Analysis of linear regression coefficients indicated significant differences as a function of FR continuity stage (F(2,18) = 18.38, p < 0.001), while the Bonferroni test revealed significant differences in slopes between stages I and III (p = 0.003), between stages I and II (p < 0.02), but not between stages II and III (p > 0.05). Interpretation The effectiveness of carpal tunnel release and the reduction in intra-carpal tunnel pressures obtained by Z-lengthening of the FR were similar to those observed after its complete division, while preserving FR continuity.

Expanded Differentiation Capability of Human Wharton's Jelly Stem Cells Toward Pluripotency: A Systematic Review.

Human Wharton's jelly stem cells (HWJSC) can be efficiently isolated from the umbilical cord, and numerous reports have demonstrated that these cells can differentiate into several cell lineages. This fact, coupled with the high proliferation potential of HWJSC, makes them a promising source of stem cells for use in tissue engineering and regenerative medicine. However, their real potentiality has not been established to date. In the present study, we carried out a systematic review to determine the multilineage differentiation potential of HWJSC. After a systematic literature search, we selected 32 publications focused on the differentiation potential of these cells. Analysis of these studies showed that HWJSC display expanded differentiation potential toward some cell types corresponding to all three embryonic cell layers (ectodermal, mesodermal, and endodermal), which is consistent with their constitutive expression of key pluripotency markers such as OCT4, SOX2, and NANOG, and the embryonic marker SSEA4. We conclude that HWJSC can be considered cells in an intermediate state between multipotentiality and pluripotentiality, since their proliferation capability is not unlimited and differentiation to all cell types has not been demonstrated thus far. These findings support the clinical use of HWJSC for the treatment of diseases affecting not only mesoderm-type tissues but also other cell lineages. Impact statement Human Wharton's jelly stem cells (HWJSC) are mesenchymal stem cells that are easy to isolate and handle, and that readily proliferate. Their wide range of differentiation capabilities supports the view that these cells can be considered pluripotent. Accordingly, HWJSC are one of the most promising cell sources for clinical applications in advanced therapies.

Scleral surgical repair through the use of nanostructured fibrin/agarose-based films in rabbits.

Scleral defects can result as a consequence of trauma, infectious diseases or cancer and surgical repair with allogeneic scleral grafts can be required. However, this method has limitations and novel alternatives are needed. Here, the efficacy of acellular nanostructured fibrin-agarose hydrogel-based substitutes (NFAH) in the repair of scleral defects in rabbits was studied. For this, scleral defects of 5-mm diameter were made on 18 adult-male New Zealand rabbits and repaired with acellular NFAH, NFAH crosslinked with genipin (NFAH-GP) or glutaraldehyde (NFAH-GA), allogeneic scleral grafts as control (C-CTR) or not repaired (negative control N-CTR) (n = 3 each). Macroscopic and histological analyses were performed after 40-days. Macroscopy confirmed the repair of all defects in a comparable manner than the C-CTR. Histology showed no degradation nor integration in C-CTR while NFAH-GP and NFAH-GA biomaterials were encapsulated by connective and inflammatory tissues with partial biodegradation. The NFAH were fully biodegraded and replaced by a loose connective tissue and sclera covering the defects. This in vivo study demonstrated that the NFAH are a promising biocompatible and pro-regenerative alternative to the use of allogeneic cadaveric grafts. However, large defects and long-term studies are needed to demonstrate the potential clinical usefulness of these substitutes.

Anatomic study of pedicled bipolar teres major transfer for irreparable posterosuperior rotator cuff tears.

BACKGROUND: Treatment of rotator cuff (RC) tears has not included bipolar muscle-tendon transfers to date. The objective of this study was to verify the feasibility of pedicled bipolar teres major (TM) transfer over and under the long head of the triceps brachii (LHT) and compare its versatility with monopolar transfer in a model of supraspinatus (SS) tears in cadavers. METHODS: In 6 shoulders of cryopreserved cadavers, we re-created complete SS tears, conducting monopolar and bipolar TM transfers over and under LHT. We compared the morphology of the SS and TM, defect coverage, angle between the transferred TM and major SS axis, and axillary nerve overlap with each technique. RESULTS: The TM and SS were morphologically similar. Defect coverage was significantly lower with monopolar transfer (12 ± 4 mm) than with bipolar transfer (39 ± 9 mm under the LHT, P = .003, and 38 ± 8 mm over the LHT, P = .004). The bipolar transfer course over the LHT was the nearest to the SS axis (39° ± 11°, P = .005). We found a greater axillary nerve overlap with bipolar transfer under the LHT (27 ± 8 mm) than with bipolar transfer over the LHT (1 ± 2 mm, P = .005) or monopolar transfer (0 mm, P < .001). CONCLUSION: Bipolar TM transfer is possible without neurovascular pedicle interference, obtaining greater RC defect coverage and the closest path to the SS axis when conducted over the LHT compared with monopolar or bipolar transfer under the LHT. Accordingly, it can be considered an alternative option for the treatment of posterosuperior RC defects.

Generation of genipin cross-linked fibrin-agarose hydrogel tissue-like models for tissue engineering applications.

The generation of biomimetic and biocompatible artificial tissues is the basic research objective for tissue engineering (TE). In this sense, the biofabrication of scaffolds that resemble the tissues' extracellular matrix is an essential aim in this field. Uncompressed and nanostructured fibrin-agarose hydrogels (FAH and NFAH, respectively) have emerged as promising scaffolds in TE, but their structure and biomechanical properties must be improved in order to broaden their TE applications. Here, we generated and characterized novel membrane-like models with increased structural and biomechanical properties based on the chemical cross-linking of FAH and NFAH with genipin (GP at 0.1%, 0.25%, 0.5% and 0.75%). Furthermore, the scaffolds were subjected to rheological (G, G', G″ modulus), ultrastructural and ex vivo biocompatibility analyses. Results showed that all GP concentrations increased the stiffness (G) and especially the elasticity (G') of FAH and NFAH. Ultrastructural analyses demonstrated that GP and nanostructuration of FAH allowed us to control the porosity of FAH. In addition, biological studies revealed that higher concentration of GP (0.75%) started to compromise the cell function and viability. Finally, this study demonstrated the possibility to generate natural and biocompatible FAH and NFAH with improved structural and biomechanical properties by using 0.1%-0.5% of GP. However, further in vivo studies are needed in order to demonstrate the biocompatibility, biodegradability and regeneration capability of these cross-linked scaffolds.

Sleep quality and its association with postural stability and fear of falling among Spanish postmenopausal women.

OBJECTIVE: To analyze the association of sleep quality with postural balance, as measured with objective stabilometric parameters, and fear of falling (FoF), among Spanish postmenopausal women. METHODS: In all, 250 women (60 ±â€Š8 years) took part in this cross-sectional study. Sociodemographic and anthropometric data were collected, as well as information concerning history of falls and FoF. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale, and the Pittsburgh Sleep Quality Index was used to analyze sleep quality. Measurements of sway area (S), velocity (V), and mediolateral (RMSX) and anteroposterior (RMSY) displacements of the center of pressure were obtained with a resistive multisensor platform under both eyes-open (EO) and eyes-closed (EC) conditions to assess postural control. The independent associations of sleep quality with FoF and postural control were evaluated by multivariate linear and logistic regressions, respectively, adjusting for potential confounding variables. RESULTS: SEO was independently associated (adjusted R = 0.073) with sleep duration (P < 0.001) and subjective sleep quality (P = 0.001), VEO (adjusted R = 0.156) with daytime dysfunction (P = 0.006) and sleep duration (P = 0.013), RMSXEO (adjusted R = 0.118) with subjective sleep quality (P = 0.005), and RMSYEO (adjusted R = 0.166) with sleep duration (P = 0.001) and daytime dysfunction (P = 0.046). Under EC condition, SEC (adjusted R = 0.014) was independently related with anxiety (P = 0.034), VEC (adjusted R = 0.148) with daytime dysfunction (P = 0.002) and sleep duration (P = 0.024), RMSXEC (adjusted R = 0.134) with subjective sleep quality (P < 0.001), and RMSYEC (adjusted R = 0.128) with sleep duration (P = 0.013) and daytime dysfunction (P = 0.033). Logistic regression showed that time since menopause (P = 0.003), body mass index (P = 0.001), and anxiety (P < 0.001), unlike sleep quality, were independently associated with FoF. The effect size of the model was medium (adjusted R= 0.162). CONCLUSIONS: In Spanish postmenopausal women, sleep duration, subjective sleep quality, and daytime dysfunction were independent risk factors for worsened postural stability. FoF, anxiety, time since menopause onset, and body mass index, unlike sleep quality, were independently associated with poor postural stability.

Development of the human shoulder joint during the embryonic and early fetal stages: anatomical considerations for clinical practice.

Although several studies have been published regarding the morphology and anatomical variations of the human shoulder joint, most have dealt with adult individuals. Those looking into the development of the joint have been focused on specific structures or have observed specimens in advanced gestational stages. The goal of this paper is to perform a complete analysis of the embryonic and early fetal development of the elements in the shoulder joint, and to clarify some contradictory data in the literature. In our study, serial sections of 32 human embryos (Carnegie stages 16-23) and 26 fetuses (9-13 weeks) were analyzed. The chondrogenic anlagen of the humerus and the medial border of the scapula can be observed from as early as Carnegie stage 17, whereas that of the rest of the scapula appears at stage 18. The osteogenic process begins in week 10 for the humeral head and week 11 for the scapula. At stage 19 the interzone becomes apparent, which will form the glenohumeral joint. In the next stage the glenohumeral joint will begin delaminating and exhibiting a looser central band. Denser lateral bands will join the humeral head (caput humeri) and the margins of the articular surface of the scapula, thus forming the glenoid labrum, which can be fully appreciated by stage 22. In 24-mm embryos (stage 21) we can observe, for the first time, the long head of the biceps tendon (which is already inserted in the glenoid labrum by week 9), and the intertubercular sulcus, whose depth is apparent since week 12. Regarding ligamentous structures, the coracohumeral ligament is observed at the end of Carnegie stage 23, whereas the primitive glenohumeral ligament already appeared in week 10. The results of this study provide a detailed description of the morphogenesis, origin and chronological order of appearance of the main intrinsic structures of the human shoulder joint during late embryonic and early fetal development. We expect these results to help explain several functional aspects of the shoulder joint, and to clarify some contradictory data in the literature regarding this complex anatomical and biomechanical structure, helping future researchers in their efforts.

Sarcopenia and sarcopenic obesity in Spanish community-dwelling middle-aged and older women: Association with balance confidence, fear of falling and fall risk.

OBJECTIVES: To analyze the association of sarcopenia, obesity, and sarcopenic obesity (SO) with fear of falling (FoF) and balance confidence in a Spanish sample of middle-aged and older community-dwelling women. STUDY DESIGN AND OUTCOME MEASURES: A total of 235 women (69.21±7.56 years) participated in this study. Body composition (bioelectrical impedance analysis), hand-grip strength, and physical performance (gait speed) were evaluated for the diagnosis of sarcopenia, obesity, and SO. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale. The Activities-Specific Balance Confidence Scale (ABC) and the Falls Efficacy Scale-International (FES-I) were employed to assess FoF and balance confidence, respectively. Scores of >26 on the FES-I and <67% on the ABC were used to identify women at risk of falling. The independent associations of sarcopenia, obesity and SO with FoF, balance confidence, and fall risk were evaluated by multivariate linear and logistic regressions, adjusting for potential confounding variables. RESULTS: 27.23% and 18.72% of women presented with sarcopenia and SO, respectively. Gait speed, body mass index (BMI), and fall history were independently associated with ABC score (adjusted-R2=0.152) and fall risk (ABC) (adjusted-R2=0.115). FES-I score was independently associated (adjusted-R2=0.193) with fall history, gait speed, BMI, and depression, which, together with obesity (BMI) and SO, remained independent factors for fall risk measured as FES-I score (adjusted-R2=0.243). CONCLUSION: In community-dwelling middle-aged and older Spanish women, BMI, gait speed, and fall history were independently associated with FoF, balance confidence, and fall risk. Depression was related only to FoF, and, together with obesity (BMI) and SO, was an independent predictor of fall risk as assessed by the FES-I.

Predicting successful prosthetic rehabilitation in major lower-limb amputation patients: a 15-year retrospective cohort study.

OBJECTIVE: To determine and compare specific factors that could be associated and predictive with successful prosthetic rehabilitation in major lower-limb amputations. METHODS: A 15-year long (2000-2014) retrospective observational cohort study was conducted. Two different criteria were used to define successful prosthetic rehabilitation: (1) the ability to walk at least 45m, regardless of assistive devices; and (2) walking >45m without other ambulatory aids than one cane (if required). Age, gender, comorbidities, cause and level of amputation, stump characteristics, ulcers in the preserved limb, and time between surgery and physical therapy were examined as predictors of successful prosthetic rehabilitation. RESULTS: A total of 169 patients (61.60±15.9 years) were included. Regarding walking ability with or without walking aids, the presence of ulcers in the preserved limb was individually associated with failed prosthetic rehabilitation (p<0.001), while being male (OR=0.21; 95%CI=0.06-0.80) and transtibial level of amputation (OR=6.73; 95%CI=1.92-23.64) were identified as independent predictors of failure and success, respectively. Regarding the criterion of successful rehabilitation, a shorter time until rehabilitation was individually associated with improved walking ability (p<0.013), while failure could be predicted by comorbidities (OR=0.48; 95%CI=0.29-0.78) and age groups of 65-75 years old (OR=0.19; 95%CI=0.05-0.78) and over 75 years old (OR=0.19; 95%CI=0.04-0.91). CONCLUSIONS: Regarding walking ability with or without walking aids, male gender and transtibial level of amputation are independently associated with failure and success respectively, whereas older age and comorbidities can predict failed prosthetic rehabilitation when assistive walking devices are considered. Future prospective cohort studies are needed to confirm these findings.

Aplicabilidad del sistema da Vinci en el abordaje transoral a la base del cráneo. Investigación preclínica / Applicability of the da Vinci robotic system in the skull base surgical approach. Preclinical investigation

Introducción: El papel de la cirugía robótica está claramente establecido en diversas especialidades como Urología o Cirugía General, pero no así en otras como Neurocirugía u Otorrinolaringología, y en el caso concreto de la Cirugía de base de cráneo, apenas ha pasado de una fase experimental. Objetivo: Investigar las posibilidades de la aplicación del robot quirúrgico da Vinci en cirugía transoral de base de cráneo comparándola con la experiencia de los autores en cirugía endoscópica transnasal convencional de la misma región. Métodos: se llevó a cabo un abordaje transoral transpalatino a la rinofaringe y la base del cráneo medial en 4 cabezas de cadáver criopreservadas. Se empleó el robot da Vinci, con endoscopio de 30° y 12mm de grosor, con doble cámara e iluminación doble, pinza de Maryland en el terminal izquierdo y tijera curva en el derecho, ambos de 8mm de grosor. El fresado óseo se realizó manualmente. Para el estudio anatómico de la región a abordar se emplearon cortes axiales de 0,5cm de grosor de una cabeza de cadáver plastinada. Resultados: Con los terminales del robot se alcanzaron con relativa facilidad diversas estructuras de la base del cráneo a distintos niveles de profundidad. Conclusiones: La cirugía robótica transoral con el sistema da Vinci aporta posibles ventajas sobre la cirugía endoscópica transnasal convencional en el abordaje quirúrgico de esta región

Introduction: The role of robotic surgery is well established in various specialties such as urology and general surgery, but not in others such as neurosurgery and otolaryngology. In the case of surgery of the skull base, it has just emerged from an experimental phase. Objective: To investigate possible applications of the da Vinci surgical robot in transoral skull base surgery, comparing it with the authors’ experience using conventional endoscopic transnasal surgery in the same region. Methods: A transoral transpalatal approach to the nasopharynx and medial skull base was performed on 4 cryopreserved cadaver heads. We used the da Vinci robot, a 30° standard endoscope 12mm thick, dual camera and dual illumination, Maryland forceps on the left terminal and curved scissors on the right, both 8mm thick. Bone drilling was performed manually. For the anatomical study of this region, we used 0.5cm axial slices from a plastinated cadaver head. Results: Various skull base structures at different depths were reached with relative ease with the robot terminals Conclusions: Transoral robotic surgery with the da Vinci system provides potential advantages over conventional endoscopic transnasal surgery in the surgical approach to this region

[Applicability of the da Vinci robotic system in the skull base surgical approach. Preclinical investigation]. / Aplicabilidad del sistema da Vinci en el abordaje transoral a la base del cráneo. Investigación preclínica.

INTRODUCTION: The role of robotic surgery is well established in various specialties such as urology and general surgery, but not in others such as neurosurgery and otolaryngology. In the case of surgery of the skull base, it has just emerged from an experimental phase. OBJECTIVE: To investigate possible applications of the da Vinci surgical robot in transoral skull base surgery, comparing it with the authors' experience using conventional endoscopic transnasal surgery in the same region. METHODS: A transoral transpalatal approach to the nasopharynx and medial skull base was performed on 4 cryopreserved cadaver heads. We used the da Vinci robot, a 30° standard endoscope 12mm thick, dual camera and dual illumination, Maryland forceps on the left terminal and curved scissors on the right, both 8mm thick. Bone drilling was performed manually. For the anatomical study of this region, we used 0.5cm axial slices from a plastinated cadaver head. RESULTS: Various skull base structures at different depths were reached with relative ease with the robot terminals CONCLUSIONS: Transoral robotic surgery with the da Vinci system provides potential advantages over conventional endoscopic transnasal surgery in the surgical approach to this region.

Effects of Four Formulations of Prostaglandin Analogs on Eye Surface Cells. A Comparative Study.

We evaluated the cytotoxic effects of four prostaglandin analogs (PGAs) used to treat glaucoma. First we established primary cultures of conjunctival stromal cells from healthy donors. Then cell cultures were incubated with different concentrations (0, 0.1, 1, 5, 25, 50 and 100%) of commercial formulations of bimatoprost, tafluprost, travoprost and latanoprost for increasing periods (5 and 30 min, 1 h, 6 h and 24 h) and cell survival was assessed with three different methods: WST-1, MTT and calcein/AM-ethidium homodimer-1 assays. Our results showed that all PGAs were associated with a certain level of cell damage, which correlated significantly with the concentration of PGA used, and to a lesser extent with culture time. Tafluprost tended to be less toxic than bimatoprost, travoprost and latanoprost after all culture periods. The results for WST-1, MTT and calcein/AM-ethidium homodimer-1 correlated closely. When the average lethal dose 50 was calculated, we found that the most cytotoxic drug was latanoprost, whereas tafluprost was the most sparing of the ocular surface in vitro. These results indicate the need to design novel PGAs with high effectiveness but free from the cytotoxic effects that we found, or at least to obtain drugs that are functional at low dosages. The fact that the commercial formulation of tafluprost used in this work was preservative-free may support the current tendency to eliminate preservatives from eye drops for clinical use.

Embryonic and early fetal period development and morphogenesis of human craniovertebral junction.

Several studies have focused on the cartilaginous, articular, and ligamentous development of the craniovertebral joint (CVJ), but there are no unifying criteria regarding the origin and morphogenetic timetable of the structures that make up the CVJ. In our study, serial sections of 53 human embryonic (n = 27) and fetal (n = 26) specimens from O'Rahilly stages 17-23 and 9-13 weeks, respectively, have been analyzed. Our results demonstrate that the chondrification of the pars basioccipitalis and exoccipitalis becomes observable at stage 19, and all future bones in the CVJ are in their cartilaginous form except for the future odontoid process. In addition, two chondrification centers appear for the body of the axis. From stage 21, the apical, alar, and transverse atlantal ligaments begin to acquire a ligamentous structure and the odontoid process initiates its chondrogenic phase. Stage 22 witnesses the first signs of the articular cavities of the atlanto-occipital joint, and by stage 23 all joints have cavities except for the transverse-odontoid joint, which will wait until week 9. In week 10, the ossification of the basilar part of the occipital bone begins, followed by the rest of the structures except for the odontoid process, which will start at week 13, thus completing the osteogenesis of all bones in the CVJ. The results of this study could help in establishing the anatomical basis of the normally functioning CVJ and for detecting its related pathologies, abnormalities, and malformations.

Lysophosphatidic acid pretreatment prevents micromolar atorvastatin-induced endothelial cell death and ensures the beneficial effects of high-concentration statin therapy on endothelial gene expression.

Because of the pleiotropic effects of statins, it may potentially be used as a locoregional adjuvant in vascular revascularization, tissue engineering, and regenerative procedures. Electron probe X-ray microanalyses and oligonucleotide microarrays were used to identify the global effects of micromolar concentrations of atorvastatin on the gene expression and cell viability of endothelial cells in different states of lysophosphatidic acid (LPA)-induced activation. Treatment with 1-µM atorvastatin for 24 hours significantly reduced the viability of human vascular endothelial cells (HUVECs). However, the same treatment of LPA-preactivated HUVECs produced elevated cell viability levels and an optimal vascular gene expression profile, including endothelial nitric oxide synthase overexpression, endothelin-1 repression, an anti-inflammatory genetic pattern, and upregulation of molecules involved in maintaining the endothelial barrier (vascular endothelial cadherin, claudin 5, tight junction protein 1, integrin ß4). The atorvastatin treatment also produced a repression of microRNA 21 and genes involved in cell proliferation and neointimal formation (vascular endothelial growth factor [VEGF] A, VEGF receptor 1, VEGFC). Results obtained suggest that micromolar atorvastatin therapy can enhance global endothelial function, but its effects on cell viability vary according to the baseline state of cell activation (preactivated, postactivated, or not activated). Preactivation with LPA protects HUVECs against atorvastatin-induced apoptosis and delivers optimal levels of cell viability and functionality.

Development and morphogenesis of human wrist joint during embryonic and early fetal period.

The development of the human wrist joint has been studied widely, with the main focus on carpal chondrogenesis, ligaments and triangular fibrocartilage. However, there are some discrepancies concerning the origin and morphogenetic time-table of these structures, including nerves, muscles and vascular elements. For this study we used serial sections of 57 human embryonic (n = 30) and fetal (n = 27) specimens from O'Rahilly stages 17-23 and 9-14 weeks, respectively. The following phases in carpal morphogenesis have been established: undifferentiated mesenchyme (stage 17), condensated mesenchyme (stages 18 and 19), pre-chondrogenic (stages 19 and 20) and chondrogenic (stages 21 and over). Carpal chondrification and osteogenic processes are similar, starting with capitate and hamate (stage 19) and ending with pisiform (stage 22). In week 14, a vascular bud penetrates into the lunate cartilaginous mold, early sign of the osteogenic process that will be completed after birth. In stage 18, median, ulnar and radial nerves and thenar eminence appear in the hand plate. In stage 21, there are indications of the interosseous muscles, and in stage 22 flexor digitorum superficialis, flexor digitorum profundus and lumbrical muscles, transverse carpal ligament and collateral ligaments emerge. In stage 23, the articular disc, radiocarpal and ulnocarpal ligaments and deep palmar arterial arch become visible. Radiate carpal and interosseous ligaments appear in week 9, and in week 10, dorsal radiocarpal ligament and articular capsule are evident. Finally, synovial membrane is observed in week 13. We have performed a complete analysis of the morphogenesis of the structures of the human wrist joint. Our results present new data on nervous and arterial elements and provide the basis for further investigations on anatomical pathology, comparative morphology and evolutionary anthropology.