Proof of concept of an experimental prototype for the prevention of parastomal hernia.

PURPOSE: The aim of this study was to analyse the complications and problems associated with the use of an experimental prototype designed for the prevention of parastomal hernia (PSH), one of the most frequent complications in ostomates. METHODS: A single-centre, non-comparative, proof-of-concept interventional pilot study of an experimental prototype designed to be used in conjunction with an abdominal compression binder to prevent PSH was conducted. The "Ostomy Fixation Device for Hernia Prevention" (patent P201531826) is a semi-rigid ostomy protector, to be used in conjunction with a compression binder. It is designed to adapt to the dimensions of standard ostomy bags from different brands and serves to transmit, in a localised manner, the support coming from the compression binder in the peristomal area without putting pressure on the collection bag. The main outcome measures were efficacy, safety, and patient-users' opinion/perception. RESULTS: Ten patients were studied for 12 months. Mean age was 61 years (± 11.59), 70% (7) were male, 80% (8) ostomised for colorectal cancer, 90% (9) underwent planned surgery and 80% (8) had a colostomy. EFFICACY: the incidence of HPE was 10% (1). SAFETY: no participant experienced pain, discomfort, itching, stinging, leakage, pouch detachment, allergy to components, or injury to the stoma or peristomal skin due to rubbing or pressure. 90% (n = 9) were considered "very satisfied" or "satisfied" with the device. CONCLUSIONS: An innovative device designed in collaboration between healthcare professionals and end-users has been shown to be safe and effective in reducing PSH in the group of ostomates studied.

Circulating long non-coding RNAs detection after heart transplantation and its accuracy in the diagnosis of acute cardiac rejection.

Long non-coding RNAs (lncRNAs) are closely implicated in biological processes and diseases with high inflammatory components. These molecules exhibit significant temporal and tissue specificity. However, the expression and function of lncRNAs have not been studied in patients after heart transplantation. Thus, we aimed to identify circulating lncRNAs in these patients and evaluate their diagnostic capacity as potential biomarkers for the non-invasive detection of acute cellular rejection (ACR). For them, we performed a transcriptomic study based on ncRNA-seq technology to detect lncRNAs in serum samples, matched to routine endomyocardial biopsies, from patients without rejection episode (0R, n = 12) and with mild (1R, n = 16) or moderate-severe (≥ 2R, n = 12) ACR. We identified 11,062 circulating lncRNAs in the serum of patients after heart transplantation. Moreover, 6 lncRNAs showed statistically significant expression when the different ACR grades were compared. Among them, AC008105.3, AC006525.1, AC011455.8, AL359220.1, and AC025279.1 had relevant diagnostic capacity for detection of ≥ 2R (AUC of 0.850 to 1.000) and 1R (AUC of 0.750 to 0.854) grades, along with high specificity and positive predictive values (≥ 83%). In addition, AL359220.1 and AC025279.1 were independent predictors for the presence of moderate-severe ACR (odds ratio = 31.132, p < 0.01 and C statistic = 0.939, p < 0.0001; odds ratio = 18.693, p < 0.05 and C statistic = 0.902, p < 0.001; respectively). In conclusion, we describe, for the first time, circulating lncRNAs after heart transplantation as potential candidates for non-invasive detection of ACR. AL359220.1 and AC025279.1 showed excellent diagnostic capability correlating with the severity episode and were strong independent predictors of rejection.

Altered MicroRNA Maturation in Ischemic Hearts: Implication of Hypoxia on XPO5 and DICER1 Dysregulation and RedoximiR State.

Ischemic cardiomyopathy (ICM) is associated with abnormal microRNA expression levels that involve an altered gene expression profile. However, little is known about the underlying causes of microRNA disruption in ICM and whether microRNA maturation is compromised. Therefore, we focused on microRNA maturation defects analysis and the implication of the microRNA biogenesis pathway and redox-sensitive microRNAs (redoximiRs). Transcriptomic changes were investigated via ncRNA-seq (ICM, n = 22; controls, n = 8) and mRNA-seq (ICM, n = 13; control, n = 10). The effect of hypoxia on the biogenesis of microRNAs was evaluated in the AC16 cell line. ICM patients showed a reduction in microRNA maturation compared to control (4.30 ± 0.94 au vs. 5.34 ± 1.07 au, p ˂ 0.05), accompanied by a deregulation of the microRNA biogenesis pathway: a decrease in pre-microRNA export (XPO5, FC = -1.38, p ˂ 0.05) and cytoplasmic processing (DICER, FC = -1.32, p ˂ 0.01). Both processes were regulated by hypoxia in AC16 cells (XPO5, FC = -1.65; DICER1, FC = -1.55; p ˂ 0.01; Exportin-5, FC = -1.81; Dicer, FC = -1.15; p ˂ 0.05). Patients displayed deregulation of several redoximiRs, highlighting miR-122-5p (FC = -2.41, p ˂ 0.001), which maintained a good correlation with the ejection fraction (r = 0.681, p ˂ 0.01). We evidenced a decrease in microRNA maturation mainly linked to a decrease in XPO5-mediated pre-microRNA export and DICER1-mediated processing, together with a general effect of hypoxia through deregulation of biogenesis pathway and the redoximiRs.

Application of Blended Learning to Veterinary Gross Anatomy Practical Sessions: Students' Perceptions of Their Learning Experience and Academic Outcomes.

The use of blended learning strategies is increasingly common in health sciences, including veterinary medicine; however, there are very few descriptions of these methods being applied to practicals. We describe here the application of blended learning based on the implementation of flipped classrooms with collaborative learning and gamification to the 2020-2021 veterinary medicine gross anatomy practicals at CEU Cardenal Herrera University (Spain). Students prepared for the sessions by pre-viewing videos and taking a quiz before the start. The sessions were conducted in small groups where students learned through collaborative work and reviewed their learning with a card game. A small but significant increase was observed when comparing the scores of practical exams of the locomotor apparatus with those of 2018-2019 (6.79 ± 2.22 vs. 6.38 ± 2.24, p < 0.05), while the scores were similar (7.76 ± 1.99 vs. 7.64 ± 1.92) for the organ system exams. Students' responses in a satisfaction survey were mostly positive (>80%) regarding the motivating and learning-facilitating effect of this educational method. Our work shows that the application of blended learning in anatomy practicals based on a flipped classroom and with elements of gamification and collaborative work can be an effective way to improve the learning experience of students.

Anxiety, emotions, and thoughts of veterinary medicine students during their first visit to the dissection room.

The use of cadavers is essential for veterinary anatomy learning. However, facing an animal corpse can be stressful for veterinary students because of their empathy toward animals. The objective of this study was to evaluate veterinary medicine students' emotions, feelings, and anxiety levels related to practicals with dog cadavers. Two questionnaires were administered to 1st year students (n = 168) at CEU Cardenal Herrera University in Valencia (Spain) before and after their first practical session with cadavers. The application of State-Trait Anxiety Inventory questionnaires showed that "state anxiety" decreased significantly (p < 0.05), from a score of 14.8 before the practical to 10.4 after, and that female students showed higher but not significantly different levels than males. Most (64%) of the students were not willing to donate the bodies of their pets, and those students were more stressed before the practical than their peers, although their anxiety levels significantly decreased by the end of the session. The majority of the students answered positively about emotions, such as feeling calm, safe, not nervous, relaxed and not worried before the practical, and this increased significantly to more than 80% by the end of the session. The visualization of educational videos prior to the session was evaluated positively by students. These results agree with those reported in other health science disciplines, showing that students face practical sessions with corpses in a similar way and suggesting that the use of videos can help decrease anxiety and enhance their learning experience.

Assessment, diagnosis and treatment of peristomal skin lesions by remote imaging: An expert validation study.

BACKGROUND: Prevention and treatment of peristomal skin problems should be a priority for nurses caring for ostomates, even when the assessment of lesions must be done remotely. OBJECTIVE: To measure the level of agreement on assessment, diagnosis and care indications for peristomal skin lesions using remote imaging among nurses in Spain. DESIGN: Prospective observational multicentre study to assess the diagnostic validity and inter- and intraobserver agreement between nurses in peristomal skin lesions. Data were collected between March and October 2019. SETTINGS AND PARTICIPANTS: The research sample consisted of a group of 39 nurses with expertise in the care of ostomates. METHODS: A panel of experts established a list of 24 common signs/findings, 15 diagnostic options and 35 treatment approaches for peristomal skin lesions. Three expert stoma therapy nurses compiled the clinical cases, which they described thoroughly and documented with photographs. The 39 participating nurses evaluated the cases in two rounds to measure inter and intraobserver agreement. RESULTS: A high or very high level of agreement (κ > 0.61) was observed for the following signs: encrustation, nodules, mucocutaneous separation and varicose veins; for the following diagnoses: mucocutaneous dehiscence, allergic contact dermatitis, encrustation and varicose veins (caput medusae); for the following treatments: recommending a diet rich in vitamin C/blueberries, applying acetic acid dressings, applying cold and topical tacrolimus treatment. CONCLUSIONS: The most easily identifiable lesions were those most prevalent and with visible signs. There was a lower level of agreement in identifying lesions for which photographs required additional information (laboratory data, description of signs and symptoms, type of diet and level of self-care). It is important to train nurses caring for ostomates to correctly describe ostomy-related lesions, which is important for nursing records, continuity of care and telehealth care.

Cardiac Sodium/Hydrogen Exchanger (NHE11) as a Novel Potential Target for SGLT2i in Heart Failure: A Preliminary Study.

Despite the reduction of cardiovascular events, including the risk of death, associated with sodium/glucose cotransporter 2 inhibitors (SGLT2i), their basic action remains unclear. Sodium/hydrogen exchanger (NHE) has been proposed as the mechanism of action, but there are controversies related to its function and expression in heart failure (HF). We hypothesized that sodium transported-related molecules could be altered in HF and modulated through SGLT2i. Transcriptome alterations in genes involved in sodium transport in HF were investigated in human heart samples by RNA-sequencing. NHE11 and NHE1 protein levels were determined by ELISA; the effect of empagliflozin on NHE11 and NHE1 mRNA levels in rats' left ventricular tissues was studied through RT-qPCR. We highlighted the overexpression of SLC9C2 and SCL9A1 sodium transport genes and the increase of the proteins that encode them (NHE11 and NHE1). NHE11 levels were correlated with left ventricular diameters, so we studied the effect of SGLT2i on its expression, observing that NHE11 mRNA levels were reduced in treated rats. We showed alterations in several sodium transports and reinforced the importance of these channels in HF progression. We described upregulation in NHE11 and NHE1, but only NHE11 correlated with human cardiac dysfunction, and its levels were reduced after treatment with empagliflozin. These results propose NHE11 as a potential target of SGLT2i in cardiac tissue.

Learning veterinary anatomy playing cards.

Gamification is a dynamic tool for educational transformation useful to encourage student interest and enhance learning. Here we present a study conducted to investigate the effectiveness of an educational card game developed by us in veterinary anatomy practicals to reinforce knowledge acquisition in veterinary students. A total of four sets of cards were designed, each one with different anatomical topics (structure identification, articulation and positioning, clinical anatomy, and comparative anatomy); students were arranged in small groups (7-10 students per group) and played the game at the end of each anatomy practical session, discussing the corresponding questions, randomly chosen, as a team. This activity was highly valued by students, most of whom (>80%) expressed that the game was enjoyable, challenging, helpful to improve their knowledge and understanding in clinical anatomy, and effective for anatomy exam preparation. Thus, the use of educational games in practical sessions seems to improve student engagement in the learning process individually and as a team.NEW & NOTEWORTHY The development and implementation of a card game as a training resource that allows learning veterinary anatomy in a motivating and cooperative environment, promoting teamwork, relationships, and trust and communication between colleagues, is described. Stimulating the ability to solve problems as a team has provided help to students preparing for their exams in a more dynamic and enjoyable way.

Análisis de los criterios del profesional de Enfermería sobre la aplicación de los dispositivos de ostomía en cada momento del proceso asistencial / Analysis of the criteria by Nursing professionals regarding the application of ostomy devices at each moment of the care process

Objetivo: analizar la opinión y los criterios de los profesionales de Enfermería sobre la aplicación de los dispositivos de ostomía en cada momento del proceso asistencial teniendo en cuenta las características de la ostomía y del paciente. Método: estudio descriptivo transversal multicéntrico a partir de una encuesta nacional realizada a profesionales de Enfermería implicados en el cuidado a pacientes ostomizados. Resultados: a pesar de la disponibilidad de todo tipo de dispositivos de ostomías en la mayoría de los centros, a partir del ingreso en hospitalización, se instruye al paciente habitualmente en el manejo de dispositivos de dos piezas, lo que explicaría su mayor frecuencia de uso. Discusión y conclusiones: se han encontrado exposiciones de casos clínicos o investigaciones promovidas por la industria en los que no se justifica el uso de los dispositivos empleados, sino las características de estos mismos. Realizar una encuesta de ámbito nacional ofrece una visión global de los criterios que siguen los profesionales de Enfermería en el cuidado y manejo del paciente ostomizado y en la elección y/o el cambio de dispositivo de ostomía.(AU)

Objective: to analyse the opinion and criteria by Nursing professionals regarding the application of ostomy devices at each moment of the care process, considering the characteristics of the ostomy and the patient. Method: a multicentre cross-sectional descriptive study based on a national survey conducted on Nursing professionals involved in care for ostomized patients. Results: regardless of the availability of all type of devices in most centres, patients are usually trained from their admission to hospital in the use of two-piece devices, which would explain their higher frequency of use. Discussion and conclusions: there have been clinical case reports or research studies promoted by the industry with the characteristics of the devices but no justification for their use. A nationwide survey offers an overall view of the criteria followed by Nursing professionals for the care and management of ostomized patients and their choice and/or replacement of ostomy devices.(AU)

DNMT3B System Dysregulation Contributes to the Hypomethylated State in Ischaemic Human Hearts.

A controversial understanding of the state of the DNA methylation machinery exists in ischaemic cardiomyopathy (ICM). Moreover, its relationship to other epigenetic alterations is incomplete. Therefore, we carried out an in-depth study of the DNA methylation process in human cardiac tissue. We showed a dysregulation of the DNA methylation machinery accordingly with the genome-wide hypomethylation that we observed: specifically, an overexpression of main genes involved in the elimination of methyl groups (TET1, SMUG1), and underexpression of molecules implicated in the maintenance of methylation (MBD2, UHRF1). By contrast, we found DNMT3B upregulation, a key molecule in the addition of methyl residues in DNA, and an underexpression of miR-133a-3p, an inhibitor of DNMT3B transcription. However, we found many relevant alterations that would counteract the upregulation observed, such as the overexpression of TRAF6, responsible for Dnmt3b degradation. Furthermore, we showed that molecules regulating Dnmts activity were altered; specifically, SAM/SAH ratio reduction. All these results are in concordance with the Dnmts normal function that we show. Our analysis revealed genome-wide hypomethylation along with dysregulation in the mechanisms of addition, elimination and maintenance of methyl groups in the DNA of ICM. We describe relevant alterations in the DNMT3B system, which promote a normal Dnmt3b function despite its upregulation.

Use of topical sevoflurane in pressure ulcer treatment in a double-lung transplant patient.

Pain caused by wounds of different etiology is usually treated with oral analgesics. New topical use of products such as the ether anesthetic sevoflurane shows good results for pain control and has additional benefits. Pressure ulcers are painful and patients may benefit from the use of sevoflurane. We present the case of a double-lung transplant patient with a long-standing sacral pressure ulcer with poor pain control, for which sevoflurane dressings were used. The number of pain-free hours after application, the amount of daily analgesics and the size of the wound were monitored with the mobile wound application MOWA. After several days of sevoflurane application, the patient reduced analgesic consumption, remained longer free of pain, and the size of the wound decreased. Unfortunately, the patient had serious complications due to multiple comorbidities and died before the wound healed completely. Topical use of sevoflurane in pressure ulcers may be a good option to treat pain and improve patient quality of life.

Plasma CD5L and non-invasive diagnosis of acute heart rejection.

BACKGROUND: Acute rejection is one of the most important direct contributors to mortality after heart transplantation. Advances in the development of novel non-invasive approaches for the early identification of allograft rejection are necessary. We conducted a non-targeted proteome characterization focused on identifying multiple plasmatic protein differences to evaluate their diagnostic accuracy for rejection episodes. METHODS: We included consecutive plasma samples from transplant recipients undergoing routine endomyocardial biopsies. A liquid chromatography-tandem mass spectrometry analysis using isobaric tags (tandem mass tag 10-plex) was performed and concentrations of CD5L were validated using a specific sandwich enzyme-linked immunosorbent assay. RESULTS: A total of 17 altered proteins were identified as potential markers for detecting heart transplant rejection, most involved in inflammation and immunity. CD5L, an apoptosis inhibitor expressed by macrophages, showed the best results in the proteomic analysis (n = 30). We confirm this finding in a larger patient cohort (n = 218), obtaining a great diagnostic capacity for clinically relevant rejection (≥Grade 2R: area under the curve = 0.892, p < 0.0001) and preserving the accuracy at mild rejection (Grade 1R: area under the curve = 0.774, p < 0.0001). CD5L was a strong independent predictor, with an odds ratio of 14.74 (p < 0.0001), for the presence of rejection. CONCLUSIONS: Episodes of acute cardiac allograft rejection are related to significant changes in a key inhibitor of apoptosis in macrophages, CD5L. Because of its precision to detect acute cellular rejection, even at mild grade, we propose CD5L as a potential candidate to be included in the studies of molecule combination panel assays. This finding could contribute to improving the diagnostic and preventive methods for the surveillance of cardiac transplanted patients.

XPO1 Gene Therapy Attenuates Cardiac Dysfunction in Rats with Chronic Induced Myocardial Infarction.

Transcriptomic signature of XPO1 was highly expressed and inversely related to left ventricular function in ischemic cardiomyopathy patients. We hypothesized that treatment with AAV9-shXPO1 attenuates left ventricular dysfunction and remodeling in a myocardial infarction rat model. We induced myocardial infarction by coronary ligation in Sprague-Dawley rats (n = 10), which received AAV9-shXPO1 (n = 5) or placebo AAV9-scramble (n = 5) treatment. Serial echocardiographic assessment was performed throughout the study. After myocardial infarction, AAV9-shXPO1-treated rats showed partial recovery of left ventricular fractional shortening (16.8 ± 2.8 vs 24.6 ± 4.1%, P < 0.05) and a maintained left ventricular dimension (6.17 ± 0.95 vs 4.70 ± 0.93 mm, P < 0.05), which was not observed in non-treated rats. Furthermore, lower levels of EXP-1 (P < 0.05) and lower collagen fibers and fibrosis in cardiac tissue were observed. However, no differences were found in the IL-6 or TNFR1 plasma levels of the myocardium of AAV9-shXPO1 rats. AAV9-shXPO1 administration attenuates cardiac dysfunction and remodeling in rats after myocardial infarction, producing the gene silencing of XPO1.

Validation of the Spanish version of the Oxford Cognitive Screen (S-OCS): psychometric properties of a short cognitive stroke-specific screening tool.

OBJECTIVE:: The aim of this study is to examine the psychometric properties of the Spanish version of the Oxford Cognitive Screen in a subacute stroke population. PARTICIPANTS AND SETTING:: Fifty-seven subacute stroke outpatients and 54 healthy individuals were recruited in Alicante province, Spain. MAIN MEASURE:: The Oxford Cognitive Screen. OTHER MEASURES:: The Montreal Cognitive Assessment, the Barcelona test, and the Barthel Index. DESIGN:: A validation study was conducted to analyze the inter-rater, intra-rater, test-retest, and internal consistency of the Spanish version of the Oxford Cognitive Screen. Concurrent validity was assessed using the Montreal Cognitive Assessment and the Barcelona test, and divergent validity using the Barthel index. Discriminant indices such as the sensitivity, specificity, predictive values, and optimal cut-offs were also estimated. RESULTS:: The subtests of the Spanish version of the Oxford Cognitive Screen showed excellent estimates for the inter-reliability (intraclass correlation coefficient (ICC) = 0.790 to 1.000; rs = 0.693 to 1.000), and acceptable-good for intra-reliability (ICC = 0.181 to 0.990) and test-retest reliability ( rs = 0.173 to 0.971). Internal consistency was also excellent (standardized Cronbach's α = 0.907). Spearman correlations for the concurrent validity were low-strong ( rs = -0.193 to 0.95) and low-moderate ( rs = -0.091 to 0.443) for divergent validity. The optimal cut-offs estimated for the subtests of the Spanish version of the Oxford Cognitive Screen showed good-high specificity (66.7%-100%) and positive predictive value (67.9%-100%), and low-good sensitivity (14.8%-83.3%) and moderate-good negative predictive value (53.5%-76.6%). Discriminant power as measured by the area under the curve indicated acceptable-good values (0.397 to 0.894). CONCLUSION:: Our findings support that the Spanish version of the Oxford Cognitive Screen is a reliable and valid tool for screening cognitive impairments in subacute stroke patients.

Intercalated disc in failing hearts from patients with dilated cardiomyopathy: Its role in the depressed left ventricular function.

Alterations in myocardial structure and reduced cardiomyocyte adhesions have been previously described in dilated cardiomyopathy (DCM). We studied the transcriptome of cell adhesion molecules in these patients and their relationships with left ventricular (LV) function decay. We also visualized the intercalated disc (ID) structure and organization. The transcriptomic profile of 23 explanted LV samples was analyzed using RNA-sequencing (13 DCM, 10 control [CNT]), focusing on cell adhesion genes. Electron microscopy analysis to visualize ID structural differences and immunohistochemistry experiments of ID proteins was also performed. RT-qPCR and western blot experiments were carried out on ID components. We found 29 differentially expressed genes, most of all, constituents of the ID structure. We found that the expression of GJA3, DSP and CTNNA3 was directly associated with LV ejection fraction (r = 0.741, P = 0.004; r = 0.674, P = 0.011 and r = 0.565, P = 0.044, respectively), LV systolic (P = 0.003, P = 0.003, P = 0.028, respectively) and diastolic dimensions (P = 0.006, P = 0.001, P = 0.025, respectively). Electron microscopy micrographs showed a reduced ID convolution index and immunogold labeling of connexin 46 (GJA gene), desmoplakin (DSP gene) and catenin α-3 (CTNNA3 gene) proteins in DCM patients. Moreover, we observed that protein and mRNA levels analyzed by RT-qPCR of these ID components were diminished in DCM group. In conclusion, we report significant gene and protein expression changes and found that the ID components GJA3, DSP and CTNNA3 were highly related to LV function. Microscopic observations indicated that ID is structurally compromised in these patients. These findings give new data for understanding the ventricular depression that characterizes DCM, opening new therapeutic perspectives for these critically diseased patients.

Musculoskeletal Problems in Pianists and Their Influence on Professional Activity.

BACKGROUND: Professional musical performance requires static postures and repetitive movements that may cause musculoskeletal problems in performers. Elite pianists are especially at risk for these disorders, which may cause discomfort but also affect their work. The objective of this study was to describe the most frequent musculoskeletal problems observed in pianists, and to explore the influence of these disorders on their professional activities from the perspective of the pianists themselves. METHODS: Musculoskeletal problems were defined in accordance with the International Classification of Diseases (ICD-10), and an analysis was conducted of medical records of 183 professional pianists held by a performing arts clinic (Terrassa, Spain). In addition, in-depth interviews were conducted with 20 pianists (6 students, 12 teachers, and 2 performers), followed by content analysis of the transcripts to explore musicians' perceptions. RESULTS: We identified a total of 20 different problems, which principally involved the upper body (arms and back). Regardless of occupation or age, all respondents reported having musculoskeletal problems and that these impacted on their professional activity. Interviewees also identified a lack of support or advice on how to prevent these problems. CONCLUSION: Musculoskeletal problems, principally those involving the upper body, are very common among pianists and affect their professional activity. It is necessary to include risk prevention information starting in the early stages of musicians' training programs.

New Cell Adhesion Molecules in Human Ischemic Cardiomyopathy. PCDHGA3 Implications in Decreased Stroke Volume and Ventricular Dysfunction.

BACKGROUND: Intercalated disks are unique structures in cardiac tissue, in which adherens junctions, desmosomes, and GAP junctions co-localize, thereby facilitating cardiac muscle contraction and function. Protocadherins are involved in these junctions; however, their role in heart physiology is poorly understood. We aimed to analyze the transcriptomic profile of adhesion molecules in patients with ischemic cardiomyopathy (ICM) and relate the changes uncovered with the hemodynamic alterations and functional depression observed in these patients. METHODS AND RESULTS: Twenty-three left ventricular tissue samples from patients diagnosed with ICM (n = 13) undergoing heart transplantation and control donors (CNT, n = 10) were analyzed using RNA sequencing. Forty-two cell adhesion genes involved in cellular junctions were differentially expressed in ICM myocardium. Notably, the levels of protocadherin PCDHGA3 were related with the stroke volume (r = -0.826, P = 0.003), ejection fraction (r = -0.793, P = 0.004) and left ventricular end systolic and diastolic diameters (r = 0.867, P = 0.001; r = 0.781, P = 0.005, respectively). CONCLUSIONS: Our results support the importance of intercalated disks molecular alterations, closely involved in the contractile function, highlighting its crucial significance and showing gene expression changes not previously described. Specifically, altered PCDHGA3 gene expression was strongly associated with reduced stroke volume and ventricular dysfunction in ICM, suggesting a relevant role in hemodynamic perturbations and cardiac performance for this unexplored protocadherin.

RhoE deficiency alters postnatal subventricular zone development and the number of calbindin-expressing neurons in the olfactory bulb of mouse.

The subventricular zone represents an important reservoir of progenitor cells in the adult brain. Cells from the subventricular zone migrate along the rostral migratory stream and reach the olfactory bulb, where they originate different types of interneurons. In this work, we have analyzed the role of the small GTPase RhoE/Rnd3 in subventricular zone cell development using mice-lacking RhoE expression. Our results show that RhoE null mice display a remarkable postnatal broadening of the subventricular zone and caudal rostral migratory stream. This broadening was caused by an increase in progenitor proliferation, observed in the second postnatal week but not before, and by an altered migration of the cells, which appeared in disorganized cell arrangements that impaired the appropriate contact between cells in the rostral migratory stream. In addition, the thickness of the granule cell layer in the olfactory bulb was reduced, although the density of granule cells did not differ between wild-type and RhoE null mice. Finally, the lack of RhoE expression affected the olfactory glomeruli inducing a severe reduction of calbindin-expressing interneurons in the periglomerular layer. This was already evident in the newborns and even more pronounced 15 days later when RhoE null mice displayed 89% less cells than control mice. Our results indicate that RhoE has pleiotropic functions on subventricular cells because of its role in proliferation and tangential migration, affecting mainly the development of calbindin-expressing cells in the olfactory bulb.

Hyaluronic acid combined with mannitol to improve protection against free-radical endothelial damage: experimental model.

PURPOSE: To evaluate the protective properties of combined sodium hyaluronate 2% and mannitol 0.5% (Visiol) on the corneal endothelium in the presence of oxidative stress induced by hydrogen peroxide (H(2)O(2)). SETTING: Instituto Oftalmológico de Alicante, Universidad Miguel Hernández, Alicante, Spain. METHODS: This was an exploratory randomized controlled parallel-group, masked-assessor study of 3 sodium hyaluronate-based ophthalmic viscosurgical devices (OVDs): Visiol, Healon (sodium hyaluronate 1%), and Viscoat (sodium hyaluronate 3%-chondroitin sodium 4%). The OVDs were tested for protective effects on the endothelium following oxidative stress induced by H(2)O(2) at increased concentrations: control (lactated Ringer's solution), 1 mM, 10 mM, and 100 mM. Groups without OVD were used as controls at the same concentrations of peroxide. Each animal received the same treatment in both eyes (10 eyes per group). Endothelial cell lesion was assessed using the Janus green photometry absorbance technique. RESULTS: At 10 mM peroxide concentration, the value of endothelial cell lesion was significantly lower in the Visiol (16.8%, P=.0056), Healon (22.2%, P=.0302), and Viscoat (21.6%, P=.0336) groups than in the control group (29.4%, no OVD). There was a trend in favor of Visiol to more efficiently reduce cell lesions of the endothelium, than Healon (P=.055) and Viscoat (P=.1013). Values of endothelial cell lesion at peroxide concentrations of 1 mM and 100 mM showed the same trends than those observed at 10 mM. CONCLUSIONS: All of the OVDs tested efficiently reduced endothelial lesions against free radicals compared with the control group in which no OVD was used. The following sequence for the efficacy of endothelial cell protection was established: Visiol>Viscoat>Healon>no OVD.