[Internal validity and reliability of an instrument for evaluating quality of nursing care services for patients, nurses, and family members]. / Validación y fiabilidad de un instrumento para la evaluación de la calidad de servicios, adaptado a familiares, pacientes y personal de enfermería.

AIM: To analyze the internal validity and reliability of the instrument for evaluating the quality of services adapted to three interest groups: patients, nurses, family members, and primary caregivers. MATERIAL AND METHOD: Our research was conducted meticulously, employing a mixed methodology with two phases: qualitative, using the focus group for internal validation of the instrument, and quantitative. Subsequently, the survey was passed to the interest group of 430 patients, 525 relatives, and 298 nurses. Chronbac's alpha reliability analysis, the multiple linear regression model as a point estimator of the parameters, and exploratory factor analysis with a maximum likelihood factor using Kaiser-Meyer-Olkin to analyze the constructor and its indicators were performed to validate the adaptation. Finally, confirmatory factor analysis determines their respective measurement models' unidimensionality, validity, and reliability. RESULTS: The result shows that the factor loading of each subconstruct is more significant than 0.5 in the three models, which indicates that the aptitude indices of the model were met. In addition, the model meets the discriminant validity criteria. The behavior of the SERVPERF questionnaire was analyzed in terms of consistency, Cronbach's alpha=0.94. CONCLUSION: The scale items' discrimination concerning the questions on global satisfaction is confirmed. This shows that the instrument is valid, reliable, and useful.

Rnd3 is necessary for the correct oligodendrocyte differentiation and myelination in the central nervous system.

Rho small GTPases are proteins with key roles in the development of the central nervous system. Rnd proteins are a subfamily of Rho GTPases, characterized by their constitutive activity. Rnd3/RhoE is a member of this subfamily ubiquitously expressed in the CNS, whose specific functions during brain development are still not well defined. Since other Rho proteins have been linked to the myelination process, we study here the expression and function of Rnd3 in oligodendrocyte development. We have found that Rnd3 is expressed in a subset of oligodendrocyte precursor cells and of mature oligodendrocytes both in vivo and in vitro. We have analyzed the role of Rnd3 in myelination using mice lacking Rnd3 expression (Rnd3gt/gt mice), showing that these mice exhibit hypomyelination in the brain and a reduction in the number of mature and total oligodendrocytes in the corpus callosum and striatum. The mutants display a decreased expression of several myelin proteins and a reduction in the number of myelinated axons. In addition, myelinated axons exhibit thinner myelin sheaths. In vitro experiments using Rnd3gt/gt mutant mice showed that the differentiation of the precursor cells is altered in the absence of Rnd3 expression, suggesting that Rnd3 is directly required for the differentiation of oligodendrocytes and, in consequence, for the correct myelination of the CNS. This work shows Rnd3 as a new protein involved in oligodendrocyte maturation, opening new avenues to further study the function of Rnd3 in the development of the central nervous system and its possible involvement in demyelinating diseases.

Hepatitis C virus infection after renal transplantation.

Hepatitis C virus (HCV) infection is the main cause of liver disease after renal transplantation. Most patients have seroconverted on dialysis to positive RNA. The viral load increases during immunosuppressive therapy. The risk of developing chronic liver disease is related to the histopathologic findings, duration and severity of the disease, immunosuppression, and transplantation time. Hepatitis C virus infection can predict onset, of proteinuria and diabetes. We studied 868 patients who received renal transplants between (1987 and 2006), of whom 18.7% were seropositive for HCV. We observed a higher rate of HCV-seropositive patients related to the duration of hemodialysis therapy. Of the HCV seropositive patients, 77% had received renal allografts before 1998. There was no difference between the sexes; however, the HCV positive patients were younger. Polymerase chain reaction tests results were positive in 91.6% of the patients with HCV antibodies. The prevalence of diabetes was greater among HCV positive patients, as was as the persistence of proteinuria. Cryoglobulins were positive in 30.8%. The incidence of acute rejection episodes in the first year was similar between groups. Of the HCV-positive patients, 80.2% were treated with cyclosporine, most patients continued this therapy throughout the study. We observed no significant difference in mortality end graft survival rate between the two groups. However, renal function differed significantly at some points during the evolution of the clinical course. Renal transplantation is still the best treatment option in patients with chronic renal disease.

Dental considerations and recommendations in Eisenmenger syndrome: A report of an unusual paediatric case.

BACKGROUND: Eisenmenger syndrome (ES) is a heart cyanotic condition characterised by elevated pulmonary vascular resistance and an intra-cardiac right-to-left shunting of blood through a systemic-to-pulmonary circulation connection. Affected children usually exhibit severe hypoxia, clubbing of fingers/toes, haemoptysis, anaemia, and organ damage. CASE REPORT: During autumn 2015, the patient and her parents arrived at the paediatric dentistry clinic. The patient presented with the main complaint of generalised inflamed gingival tissues, severely protruded upper incisors, and evident abnormal mouth breathing. TREATMENT: This was performed under local analgesia, rubber-dam isolation, and antimicrobial prophylaxis with amoxicillin (50 mg/kg). The patient's parents agreed to the treatment plan through a signed informed consent. This treatment consisted of the placement of pit and fissure sealants on the four permanent first molars (which included enamel preparation with fissurotomy burs), in-depth gingiva/dental frequent cleanings, local fluoride varnish applications, and an exhaustive programme of at-home oral hygiene (brushing, flossing, and chlorhexidine mouth rinses), including adequate nutrition. Gingivoplasty surgery to remove residual enlarged tissues was indicated for the near future. FOLLOW-UP: The child did not return to the clinic. When contacted, the parents reported that their daughter's systemic condition worsened significantly. She was confined to a bed at home under palliative care, with a life-span expectation of only a few months. CONCLUSION: Comprehensive dental care of children with ES requires careful consideration of their medical condition, and dental care delivery should be coordinated with the paediatric cardiologist. General analgesia should be considered only in strictly selected cases, due to the high peri-operative mortality reported.

Intestinal Barrier and Behavior.

The intestinal barrier function contributes to gut homeostasis by modulating absorption of water, electrolytes, and nutrients from the lumen into the circulation while restricting the passage of noxious luminal substances and microorganisms. Chronic conditions such as rheumatoid arthritis, inflammatory bowel disease, and celiac disease are associated to intestinal barrier dysfunction. Here, the hypothesis is that a leaky intestinal wall allowing for indiscriminate passage of intraluminal compounds to the vascular compartment could in turn lead to systemic inflammation. An increasing number of studies are now investigating the association between gut permeability and CNS disorders, under the premise that translocation of intestinal luminal contents could affect CNS function, either directly or indirectly. Still, it is unknown whether disruption of intestinal barrier is a causative agent or a consequence in these situations. Here, we discuss the latest evidence pointing to an association between increased gut permeability and disrupted behavioral responses.

Persistence of vaccine-derived poliovirus following a mass vaccination campaign in Cuba: implications for stopping polio vaccination after global eradication.

BACKGROUND: With substantial progress made toward polio eradication, developing the appropriate strategy for discontinuing global oral poliovirus vaccine (OPV) after global eradication becomes increasingly important. At issue is the theoretical risk of independent circulation of potentially virulent OPV-derived strains. Because Cuba uses OPV only in mass campaigns, it represents an ideal site to assess vaccine-derived poliovirus persistence. METHODS: Infants born after the 1997 biannual mass campaigns were evaluated for past (neutralizing antibody) or current (virus excretion) evidence of vaccine-derived poliovirus exposure. We obtained sera and/or stool specimens from 861 infants; a second serum from 218 infants. RESULTS: All stool specimens were poliovirus negative. Of 762 infants, 113 (14.8%) had initially detectable poliovirus type 1 antibody, 193 (25.3%) type 2, and 94 (12.3%) type 3. A precipitous antibody decline occurred in initially positive sera. CONCLUSIONS: Our results suggest that in a country with high population immunity, vaccine-derived virus is unlikely to establish ongoing circulation.

A search for natural bioactive compounds in Bolivia through a multidisciplinary approach. Part I. Evaluation of the antimalarial activity of plants used by the Chacobo Indians.

Thirty extracts of plants traditionally used by the Chacobos, a native community living in the Amazonian part of Bolivia, were screened in vitro and/or in vivo for antimalarial activity. Two of the four species designated as antimalarial, Geissospermum laeve and Maquira coriacea, displayed rather good activity, corroborating their traditional uses. However, they did show a rather high toxicity in vivo. Among twelve species used to cure symptoms relevant to malaria, five showed good activity: Apuleia leiocarpa, Bauhinia guianensis, Nectandra cuspidata, Sparattanthelium amazonum, Tanaecium jaroba. Two species, Qualea paraensis and Sclerolobium aff. guianense, used to treat scabies, showed interesting antimalarial activity in vivo; three other species (Iryanthera laevis, Prunus amplifolia, Pterocarpus aff. amazonum) used for various medicinal purposes, apparently not related with a Plasmodium infection, also showed antimalarial activity. Finally, one species (Derris amazonica) used as a piscicide displayed good in vitro activity, in the same way as one Annonaceae, Guatteria aff. schomburgkiana, used for construction purposes.

Review article: intestinal barrier dysfunction and central nervous system disorders--a controversial association.

BACKGROUND: Central nervous system (CNS) development and physiopathology are greatly affected by environmental stimuli. The intestinal barrier restricts the entrance of toxins, pathogens, and antigens while modulating the expression of various neuroactive compounds. The existence of a rich gut-to-brain communication raises the possibility that intestinal barrier alterations may take part in the pathophysiology of CNS disorders. AIM: To review evidence associating intestinal barrier dysfunction with the development of CNS disorders. METHODS: Literature search was conducted on PubMed using the following terms: intestinal barrier, intestinal permeability, central nervous system, mental disorders, schizophrenia, autism, stress, anxiety, depression, and neurodegeneration. RESULTS: Clinical and animal model studies of the association between intestinal barrier and schizophrenia, autism spectrum disorders, neurodegenerative diseases or depression were reviewed. The majority of reports concentrated on schizophrenia and autism spectrum disorders. About half of these described increased intestinal permeability/mucosal damage in patients compared with healthy controls, with up to 43% of children with autism spectrum disorders and up to 35% of schizophrenia patients displaying abnormally high urinary excretion of the sugars used as permeability markers. However, another substantial group of studies did not find such differences. In autism spectrum disorders, some reports show that the use of diets such as the gluten-free casein-free diet may contribute to the normalisation of lactulose/mannitol ratio, but to date there is no adequately controlled study showing improvement in behavioural symptoms following these dietary interventions. CONCLUSIONS: Evidence of altered intestinal permeability in individuals suffering from CNS disorders is limited and cannot be regarded as proven. Moreover the efficacy of targeting gut barrier in the management of neurological and behavioural aspects of CNS disorders has not yet been established, and needs further investigation.

Evaluating the impact of gastrointestinal episodes on the health-related quality of life of solid organ transplant recipients: sensitivity to change of the SIGIT-QoL questionnaire: Mypaciente-2 study.

A significant proportion of transplant patients undergoing immunosuppressant therapy experience gastrointestinal (GI) symptoms. The SIGIT-QoL is a brief instrument developed to measure adverse gastrointestinal effects on patients' health-related quality of life (HRQoL). The goal of this study was to analyze the psychometric properties of the SIGIT-QoL that are required for its use in clinical research and practice, especially its value for detecting changes in the impact of gastrointestinal symptoms on HRQoL of solid organ transplant (SOT) recipients. To this end, an observational, multicenter, prospective study was conducted. SOT patients aged ≥18 years who had received the graft 3 to 24 months before and were experiencing gastrointestinal symptoms were evaluated at baseline, 1 to 2 weeks later, and 3 months after baseline. Sociodemographic and clinical data recorded included: age, sex, SOT type (lung, kidney, liver, or heart), acute allograft rejection, gastrointestinal etiology, Clinical Global Impressions (CGI) and Patient Global Impression (PGI) Severity of Illness (SI) and Global Improvement (GI) scores, and the SIGIT-QoL (scores range from 0 [maximum impact] to 68 [minimum disruption]). Intraclass correlation coefficients, differences between baseline and last visit (Wilcoxon test), effect size (Cohen's d), the minimal important differences (using CGI and PGI scores as anchors in General Linear Models), and the cutoff score (receiver-operating characteristic analysis) were calculated. In total, 277 SOT patients (61.4% male) were included. Mean ± SD age was 52.69 ± 11.65 years, time since transplantation was 12.31 ± 6.74 months, and 22.4% experienced an acute allograft rejection. At baseline, total SIGIT-QoL mean scores (51.21 ± 11.25) showed an impact on patients' HRQoL that was diminished 3 months later (57.40 ± 8.38; P < .001). SIGIT-QoL test-retest reliability was adequate (intraclass correlation coefficient, 0.740-0.895). A moderate effect size (d = -0.550) was found. Moreover, a minimal important difference of 4.2 points in total scores was found (F4,223 = 16.917 [P < .001] and F4,224 = 25.138 [P < .001]). Finally, a cutoff point (55.00 points) was estimated (area under the concentration-time curve, 0.846 [95% confidence interval, 0.798-0.894], P < .001; sensitivity, 0.793; specificity, 0.713; negative likelihood ratio, 0.290; positive likelihood ratio, 2.762). We concluded that the SIGIT-QoL is a feasible (average completion time, <6.5 minutes), reliable, and valid instrument for assessing the impact of gastrointestinal symptoms on the HRQoL of SOT patients.

Role of Shh in the development of molecularly characterized tegmental nuclei in mouse rhombomere 1.

Hindbrain rhombomeres in general are differentially specified molecularly by unique combinations of Hox genes with other developmental genes. Rhombomere 1 displays special features, including absence of Hox gene expression. It lies within the hindbrain range of the Engrailed genes (En1, En2), controlled by the isthmic organizer via diffusion of FGF8. It is limited rostrally by the isthmus territory, and caudally by rhombomere 2. It is double the normal size of any other rhombomere. Its dorsal part generates the cerebellar hemispheres and its ventral part gives rise to several populations, such as some raphe nuclei, the interpeduncular nucleus, the rhabdoid nucleus, anterior, dorsal, ventral and posterodorsal tegmental nuclei, the cholinergic pedunculopontine and laterodorsal tegmental nuclei, rostral parts of the hindbrain reticular formation, the locus coeruleus, and part of the lateral lemniscal and paralemniscal nuclei, among other formations. Some of these populations migrate tangentially before reaching their final positions. The morphogen Sonic Hedgehog (Shh) is normally released from the local floor plate and underlying notochord. In the present report we explore, first, whether Shh is required in the specification of these r1 populations, and, second, its possible role in the guidance of tangentially migrating neurons that approach the midline. Our results indicate that when Shh function is altered selectively in a conditional mutant mouse strain, most populations normally generated in the medial basal plate of r1 are completely absent. Moreover, the relocation of some neurons that normally originate in the alar plate and migrate tangentially into the medial basal plate is variously altered. In contrast, neurons that migrate radially (or first tangentially and then radially) into the lateral basal plate were not significantly affected.

Mesencephalic neuronal populations: new insights on the ventral differentiation programs.

The midbrain is a complex structure where different functions are located. This formation is mainly involved in the visual and auditory information process (tectum) and visual movements and motor coordination (tegmentum). Here we display a complete description of midbrain anatomy based on the prosomeric model and of the developmental events that take place to generate this structure. We also summarize the new data about the differentiation and specification of the basal populations of the midbrain. The neural tube suffers the influence of several secondary organizers. These signaling centers confer exact positional information to the neuroblasts. In the midbrain these centers are the Isthmic organizer for the antero-posterior axis and the floor and roof plates for the dorso-ventral axis. This segment of the brain contains, in the dorsal part, structures such as the collicula (superior and inferior), tectal grey and the preisthmic segment, and in the basal plate, neuronal populations such as the oculomotor complex, the dopaminergic substantia nigra and the ventral tegmental area, the reticular formation and the periacueductal grey. Knowledge of the genetic cascades involved in the differentiation programs of the diverse populations will be extremely important to understand not only how the midbrain develops, but how degenerative pathologies, such as Parkinson's disease, occurs. These cascades are triggered by signaling molecules such as Shh, Fgf8 or Wnt1 and are integrated by receptor complexes and transcription factors. These are directly responsible for the induction or repression of the differentiation programs that will produce a specific neuronal phenotype.

Identification of sperm subpopulations with defined motility characteristics in ejaculates from Ile de France rams.

The aims of this study were to identify different motile sperm subpopulations in fresh ejaculates from six Ile de France rams, by using a computer-assisted sperm motility analysis (CASA) system, and to evaluate the effects of individual ram and season on population distribution. Overall sperm motility and individual kinematic parameters of motile spermatozoa were evaluated for 125,312 spermatozoa, defined by curvilinear velocity (VCL), linear velocity (VSL), average path velocity (VAP), linearity coefficient (LIN), straightness coefficient (STR), wobble coefficient (WOB), mean amplitude of lateral head displacement (ALH) and frequency of head displacement (BCF). A multivariate cluster analysis was carried out to classify these spermatozoa into a reduced number of subpopulations according to their movement patterns. The statistical analysis clustered the whole motile sperm population into five separate groups: subpopulation 1, constituted by rapid, progressive and non sinuous spermatozoa (VCL=126.41 µm/s, STR=92.87% and LIN=86.47%); subpopulation 2, characterized by progressive spermatozoa with moderate velocity (VCL=74.74 µm/s and STR=84.03%); subpopulation 3, represented by rapid, progressive and sinuous spermatozoa (VCL=130.45 µm/s, STR=76.02% and LIN=47.68%); subpopulation 4 represents rapid nonprogressive spermatozoa (VCL=128.69 µm/s and STR=44.09%); subpopulation 5 includes poorly motile, nonprogressive spermatozoa with a very irregular trajectory (VCL=36.81 µm/s and STR=47.04%). Our results show the existence of five subpopulations of motile spermatozoa in ram ejaculates. The frequency distribution of spermatozoa within subpopulations was quite similar for the six rams, and the five subpopulations turned out to be very stable along seasons.

A novel role for the metabotropic glutamate receptor-7: modulation of faecal water content and colonic electrolyte transport in the mouse.

BACKGROUND AND PURPOSE: Increasing evidence implicates metabotropic glutamate receptor mGlu(7) in the pathophysiology of stress-related disorders such as depression and anxiety. Mood disorders are frequently associated with gastrointestinal (GI) dysfunction; however, the role of mGlu(7) receptors outside the CNS is unknown. This present study investigated the expression and possible functional role of mGlu(7) receptors in the mouse colon. EXPERIMENTAL APPROACH: Expression of mGlu(7) receptor mRNA and protein was studied in mouse colon by in situ hybridization and Western blotting. Effects of the selective mGlu(7) receptor agonist AMN082 on defecation and faecal parameters were studied in an isolation-induced stress model. AMN082 effects on ion transport and neuronal intracellular signalling were examined via Ussing chambers and calcium imaging. KEY RESULTS: mGlu(7) receptor mRNA and protein were highly expressed in colon mucosa. Stress-induced faecal output was unaffected by AMN082, although faecal water content was increased. In mucosa/submucosa preparations, 100 nM and 1 microM AMN082 increased bethanechol-induced changes in short-circuit current in the Ussing chamber. This was sensitive to tetrodotoxin. Also, 100 nM AMN082 significantly increased calcium signalling in a subset of submucosal neurons. CONCLUSIONS AND IMPLICATIONS: Activating mGlu(7) receptors increased colonic secretory function in vivo and ex vivo. In a group of submucosal neurons, AMN082 strongly induced calcium signalling and the presence of submucosal nerves was required for the AMN082-dependent increase in secretion. These data suggest that targeting mGlu(7) receptors may be useful in the treatment of central components of stress disorders and also stress-associated GI dysfunction such as diarrhoea or constipation.

Comparison of the antidepressant sertraline on differential depression-like behaviors elicited by restraint stress and repeated corticosterone administration.

Depressive disorder involves emotional, cognitive, autonomic and endocrine alterations and also evidences support the role of stress in the development of this disorder. Because the hypothalamic-pituitary-adrenal axis is involved in the stress response with a concomitant rise in plasma corticoids, the present study compares the antidepressant effects of sertraline (10mg/kg, i.p.) on behavioral changes elicited by (i) restraint stress (2.5h/day for 13days) and (ii) corticosterone injections (30mg/kg, s.c., for 13days). Stressed animals, but not corticosterone-treated animals displayed anxiety behavior and a reduction in the acquisition of a conditioned avoidance response to 25% of control levels (8.0±2.2 vs. 31.7±3.2), being this effect partly sensitive to sertraline. Stressed, but not corticosterone-treated, animals displayed an increased escape failure compared with the control group (24.6%±3.5 vs. 1.6±0.7), an effect partly prevented by sertraline treatment (7.3%±2.0). Both stressed rats and corticosterone-treated rats showed an increase in immobility in the forced swim test, an effect prevented by sertraline. These results suggest that the altered behaviors elicited by stress and corticosterone can be explained by neural modifications that are sensitive to the sertraline antidepressant.

Reduced natriuresis after oral sodium load in cholestatic rats: role of compartment volumes and ANP.

The purpose of this study was to assess the participation of the atrial natriuretic peptide (ANP)-cGMP system in electrolyte and volume handling of cholestatic rats submitted to an acute oral sodium load. Cholestasis was induced by ligation and section of the common bile duct (n = 51). Control rats were sham operated (n = 56). Three weeks after surgery, 24-hr urinary volume, sodium, potassium, cGMP and creatinine excretion were measured. Three days later, animals received 10 mmol/kg NaCl (1 M) by gavage, and urinary excretion was measured for 6 hr. In parallel groups of rats, plasma volume, electrolytes and ANP concentration, extracellular fluid volume (ECFV), and renal medullary ANP-induced cGMP production were determined in basal conditions or 1 hr after oral sodium overload. As compared with controls, cholestatic rats had a larger ECFV and higher plasma ANP (67.2 +/- 5.2 vs 39.7 +/- 3.5 pg/ml), but lower hematocrit and blood volume, and were hyponatremic. Cholestatic rats showed higher basal excretion of sodium, potassium, and volume than controls, but equal urinary cGMP. After the NaCl overload, cholestatic rats showed a reduced sodium excretion but equal urinary cGMP. One hr after sodium overload, both groups showed hypernatremia, but whereas in control rats ECFV and ANP increased (50.7 +/- 4.1 pg/ml), in cholestatic rats ECFV was unchanged, and plasma volume and ANP were reduced (37.5 +/- 5.8 pg/ml). ANP-induced cGMP production in renal medulla was similar in cholestatic and control nonloaded rats (14.2 +/- 5.2 vs 13.4 +/- 2.6 fmol/min/mg). One hr after the load, medullary cGMP production rose significantly in both groups, without difference between them (20.6 +/- 3.1 vs 22.7 +/- 1. 7 fmol/min/mg). We conclude that the blunted excretion of an acute oral sodium load in cholestatic rats is associated with lower plasma ANP due to differences in body fluid distribution and cannot be explained by renal refractoriness to ANP.

Interactions between bradykinin and ANP in rat kidney in vitro: inhibition of natriuresis and modulation of medullary cyclic GMP.

In anesthetized rats, the renal excretory actions of atrial natriuretic peptide (ANP) are inhibited by intravenous or intraperitoneal injections of bradykinin. To elucidate the mechanisms underlying this inhibition, we evaluated bradykinin effects on: i- ANP-induced natriuresis and diuresis in isolated perfused rat kidneys, and ii- ANP-induced cGMP production in rat renal medulla in vitro. In perfused kidneys, 1 microgram bradykinin completely inhibited the diuretic and natriuretic responses elicited by 0.5 microgram ANP, without changes in perfusion pressure. The inhibitory effects of bradykinin were abolished by HOE-140, a kinin-B2 receptor antagonist. Bradykinin alone had no effect on urinary excretion or perfusion pressure. Incubation with ANP (0.1 nM to 1 microM) increased renal medullary cGMP content up to 30-fold, in a concentration-dependent fashion. Medullary cGMP was moderately increased by the nitric oxide donor, sodium nitroprusside (1 microM), but it was unchanged by bradykinin (0.1 nM-0.1 microM). Despite this, ANP-induced cGMP production was significantly enhanced by co-incubation with low concentrations of bradykinin (up to 0.1 nM). In contrast, ANP-induced cGMP accumulation was unchanged by concentrations of 1 nM bradykinin or higher. In the presence of 100 nM HOE-140, bradykinin (0.1-1 nM) did not affect ANP-induced cGMP production. These results demonstrate that bradykinin counteracts ANP-stimulated sodium and water excretion, by acting directly on the kidney. The interaction between both peptides is complex; our data suggest that renal medullary ANP receptors are subjected to an on/off modulation by fluctuating bradykinin concentrations.