Handwritten Geometrical Patterns in the Evaluation of Motor Symptoms in Psychotic Disorders.

The analysis of handwriting has been used in several contexts. For example, handwriting has shown to be of value in the study of motor symptoms in neurological and mental disorders. In the present work, the geometric analysis of handwriting patterns is proposed as a tool to evaluate motor symptoms in psychotic disorders. Specifically, we have employed the lacunarity, a measure of the heterogeneity of a spatial structure. Forty-two patients with a psychotic disorder and 35 matched healthy controls participated in the study. Participants were asked to copy some patterns with a pen on a white paper. The results showed that lacunarity was significantly higher in handwritten patterns from patients than from controls. In addition, we found higher values of lacunarity in handwritten patterns from patients with severe motor symptoms in comparison with patients with mild or absent motor symptoms. Lacunarity of handwritten patterns was significantly correlated with clinical scores of rigidity. In conclusion we argue that the heterogeneity of handwritten patterns could be used as a simple and objective measure of motor symptoms.

Fractal characterization of internally and externally generated conscious experiences.

Although there is an extensive literature on the study of the neural correlates of consciousness (NCC) this is a subject that is far from being considered over. In this paper we present a novel experimental paradigm, based on binocular rivalry, to study internally and externally generated conscious experiences. We called this procedure bimodal rivalry. In addition, and assuming the non-linear nature of the EEG signals, we propose the use of fractal dimension to characterize the complexity of the EEG signal associated with each percept. Analysis of the data showed a significant difference in complexity between the internally generated and externally generated percepts. Moreover, EEG complexity was dissimilar for externally generated auditory and visual percepts. These results support fractal dimension analyses as a new tool to characterize conscious perception.

Social mobility and healthy behaviours from a gender perspective in the Spanish multicase-control study (MCC-Spain).

There is evidence for the influence of socioeconomic status (SES) on healthy behaviours but the effect of social mobility (SM) is not yet well known. This study aims to analyse the influence of origin and destination SES (O-SES and D-SES) and SM on healthy behaviours and co-occurrence, from an integrated gender and age perspective. Data were obtained from the controls of MCC-Spain between 2008-2013 (3,606 participants). Healthy behaviours considered: healthy diet, moderate alcohol consumption, non-smoking and physical activity. SM was categorized as stable high, upward, stable medium, downward or stable low. Binary and multinomial logistic regression models were adjusted. Those aged <65, with a low O-SES, D-SES and stable low SM are less likely to have healthy behaviours in the case of both women (physically active: OR = 0.65 CI = 0.45-0.94, OR = 0.71 CI = 0.52-0.98, OR = 0.61 CI = 0.41-0.91) and men (non-smokers: OR = 0.44 CI = 0.26-0.76, OR = 0.54 CI = 0.35-0.83, OR = 0.41 CI 0.24-0.72; physically active: OR = 0.57 CI = 0.35-0.92, OR = 0.64 CI = 0.44-0.95, OR = 0.53 CI = 0.23-0.87). However, for those aged ≥65, this probability is higher in women with a low O-SES and D-SES (non-smoker: OR = 8.09 CI = 4.18-15.67, OR = 4.14 CI = 2.28-7.52; moderate alcohol consumption: OR = 3.00 CI = 1.45-6.24, OR = 2.83 CI = 1.49-5.37) and in men with a stable low SM (physically active: OR = 1.52 CI = 1.02-1.26). In the case of men, the same behaviour pattern is observed in those with a low O-SES as those with upward mobility, with a higher probability of co-occurring behaviours (three-to-four behaviours: OR = 2.00 CI = 1.22-3.29; OR = 3.13 CI = 1.31-7.48). The relationship of O-SES, D-SES and SM with healthy behaviours is complex and differs according to age and gender.

Andalusian Registry for familial adenomatous polyposis. Analysis of patients included.

OBJECTIVE: To evaluate the phenotype and genotype characteristic of patients included in the Andalusian Registry for familial adenomatous polyposis, the genotype/phenotype correlation and the impact of Registry in the frequency of colorectal cancer of registered. MATERIAL AND METHODS: A descriptive study of 77 patients with FAP belonging to 33 families, included in a centralized database visited by the physicians of the hospitals taking part in the present study, on prior signing of confidentiality letters. All genetic studies were carried out in the Immunology Service of our institution. RESULTS: We have included in our study 77 patients of 33 families; 31 probands with a mean age of 32 years (13-51) and 46 relatives at risk with a mean age of 21.8 years (6-55). Genetic study informed in 68/77 with positive result in 92.6%. Ten probands showed colorectal cancer (CRC) at the time of diagnosis (32.2%). Only two affected relatives showed CRC at diagnosis (4.3%), a statistically significant difference (p < 0.05). Gastrointestinal involvement was observed in 30/61 (49%), desmoid tumors in 7/77 (9.1%) and congenital hypertrophy of the retinal pigment epithelium in 23/55 (65.7%). 86.7% of patients with this alteration showed mutations between codons 454 and 1019, with a statistically significant correlation ((p < 0.05). CONCLUSIONS: The registry has facilitated the genetic diagnosis for all affected families disregard their province of origin. It has also improved the screening of affected relatives and has made it possible to take preventive measures immediately, therefore diminishing the incidence of CRC at diagnosis in registered affected relatives. The correlation between congenital hypertrophy of the retinal pigment epithelium with some mutations is the only phenotypic-genotypic correlation with statistical significance.

Introspective and Neurophysiological Measures of Mind Wandering in Schizophrenia.

Patients with schizophrenia have often been considered to be "in their own world". However, this casual observation has not been proven by scientific evidence so far. This can be explained because scientific research has usually addressed cognition related to the processing of external stimuli, but only recently have efforts been made to explain thoughts, images and feelings not directly related to the external environment. This internally directed cognition has been called mind wandering. In this paper, we have explored mind wandering in schizophrenia under the hypothesis that a predominance of mind wandering would be a core dysfunction in this disorder. To this end, we collected verbal reports and measured electrophysiological signals from patients with schizophrenia spectrum disorders and matched healthy controls while they were presented with segments of films. The results showed that mind wandering was more frequent in patients than in controls. This higher frequency of mind wandering did not correlate with deficits in attentional, memory or executive functioning. In addition, mind wandering in patients was characterized by a different pattern of Electroencephalography (EEG) complexity in patients than in controls, leading to the suggestion that mind wandering in schizophrenia could be of a different nature. These findings could have relevant implications for the conceptualization of this severe mental disorder.

Contributions of throughfall, forest and soil characteristics to near-surface soil water-content variability at the plot scale in a mountainous Mediterranean area.

Soil water-content (SWC) variability in forest ecosystems is affected by complex interactions between climate, topography, forest structure and soil factors. However, detailed studies taking into account the combined effects of these factors are scarce. This study's main aims were to examine the control that throughfall exerts on local spatial variation of near-surface soil water-content and to combine this information with forest structure and soil characteristics, in order to analyze all their effects together. Two stands located in the Vallcebre Research Catchments (NE Spain) were studied: one dominated by Quercus pubescens and the other by Pinus sylvestris. Throughfall and the related shallow SWC were monitored in each plot in 20 selected locations. The main characteristics of the nearest tree and soil parameters were also measured. The results indicated that mean SWC increment at the rainfall event scale showed a strong linear relationship with mean throughfall amount in both forest plots. The % of locations with SWC increments increased in a similar way to throughfall amount in both forest plots. The analyses considering all the effects together indicated again that throughfall had a significant positive effect in both forest plots, while soil litter depth showed a significant negative effect for the oak plot but lower statistical significance for the pine plot, showing a comparable -although more erratic- influence of the organic forest floor for this plot. These results, together with lower responses of SWC to throughfall than expected in rainfall events characterized by low preceding soil water-condition and high rainfall intensity, suggest that litter layer is playing an important role in controlling the soil water-content dynamics. The biometric characteristics of the nearest trees showed significant but very weak relationships with soil water-content increment, suggesting that stemflow and throughfall may act at lower distances from tree trunk than those presented in our study.

Fractal dimension analysis of states of consciousness and unconsciousness using transcranial magnetic stimulation.

BACKGROUND AND OBJECTIVE: Knowing whether a subject is conscious or not is a current challenge with a deep potential clinical impact. Recent theoretical considerations suggest that consciousness is linked to the complexity of distributed interactions within the corticothalamic system. The fractal dimension (FD) is a quantitative parameter that has been extensively used to analyse the complexity of structural and functional patterns of the human brain. In this study we investigate FD to assess whether it can discriminate between consciousness and different states of unconsciousness in healthy individuals. METHODS: We study 69 high-density electroencephalogram (hd-EEG) measurements after transcranial magnetic stimulation (TMS) in 18 healthy subjects progressing from wakefulness to non-rapid eye movement (NREM) sleep and sedation induced by different anaesthetic agents (xenon and propofol). We quantify the integration of thalamocortical networks by calculating the FD of a spatiotemporal voxelization obtained from the locations of all sources that are significantly activated by the perturbation (4DFD). Moreover, we study the temporal evolution of the evoked spatial distributions and compute a measure of the differentiation of the response by means of the Higuchi FD (HFD). Finally, a Fractal Dimension Index (FDI) of perturbational complexity is computed as the product of both quantities: integration FD (4DFD) and differentiation FD (HFD). RESULTS: We found that FDI is significantly lower in sleep and sedation when compared to wakefulness and provides an almost perfect intra-subject discrimination between conscious and unconscious states. CONCLUSIONS: These results support the combination of FD measures of cortical integration and cortical differentiation as a novel paradigm of tracking complex spatiotemporal dynamics in the brain that could provide further insights into the link between complexity and the brain's capacity to sustain consciousness.

Spatial Analysis of Handwritten Texts as a Marker of Cognitive Control.

We explore the idea that cognitive demands of the handwriting would influence the degree of automaticity of the handwriting process, which in turn would affect the geometric parameters of texts. We compared the heterogeneity of handwritten texts in tasks with different cognitive demands; the heterogeneity of texts was analyzed with lacunarity, a measure of geometrical invariance. In Experiment 1, we asked participants to perform two tasks that varied in cognitive demands: transcription and exposition about an autobiographical episode. Lacunarity was significantly lower in transcription. In Experiment 2, we compared a veridical and a fictitious version of a personal event. Lacunarity was lower in veridical texts. We contend that differences in lacunarity of handwritten texts reveal the degree of automaticity in handwriting.

The NRF2 transcription factor plays a dual role in colorectal cancer: A systematic review.

BACKGROUND: Colorectal cancer is one of the most common cancers worldwide, and is influenced by the interplay of various factors, including a very strong genetic component. For instance, incorrect mitochondrial biogenesis is correlated with increased risk of developing colorectal cancer. Thus, it is important to understand the consequences of changes in both the expression and the correct function of the transcription factors that regulate mitochondrial biogenesis, namely NRF2. OBJECTIVES: The main objective of this paper is to characterise the relationship between NRF2 and colorectal cancer by compiling data from an exhaustive literature search. METHODS: Information was obtained by defining specific search terms and searching in several databases. After a strict selection procedure, data were tabulated and the relationships between articles were assessed by measuring heterogeneity and by constructing conceptual maps. RESULTS AND DISCUSSION: We found a general consensus in the literature that the presence of oxidizing agents as well as the inhibition of the NRF2 repressor Keap1 maintain NRF2 expression at basal levels. This predominantly exerts a cytoprotective effect on cells and decreases risk of colorectal cancer. However, if NRF2 is inhibited, protection against external agents disappears and risk of colorectal cancer increases. Interestingly, colorectal cancer risk is also increased when NRF2 becomes overexpressed. In this case, the increased risk arises from NRF2-induced inflammation and resistance to chemotherapy. CONCLUSION: The proper basal function of NRF2 and Keap1 are essential for preventing oncogenic processes in the colon. Consequently, any disruption to the expression of these genes can promote the genesis and progression of colon cancer.

Comparative study of hyaluronic derivatives: rheological behaviour, mechanical and chemical degradation.

Depolymerisation by oxytetracycline (OTC) as well as the progressive cleavage of hyaluronic acid induced by ultrasound was investigated in nine commercially available hyaluronic polymers. Sample solutions differed in molecular weight, from 500 to 7000 kDa, and in their source. The hyaluronic acid concentration in each sample was analysed by HPLC. The concentration range was over 8.39-10.18 mg ml(-1) in samples with a nominal concentration of 1%, and 14.05 mg ml(-1) in one sample with a nominal concentration of 1.5%. It was found that stability was dependent on both molecular weight and the concentration of the samples. The rheological parameters n (power law index) and K (consistency coefficient) were good predictors regarding the degradation behaviour. Although many factors are involved in obtaining a therapeutic response, the results obtained in this work support the notion that both mechanical and chemical degradation are reduced in hyaluronate solutions with low molecular weight, the final concentration of the product being a critical factor.

[Duodenal perforation due to an endoscopic biliary prosthesis]. / Perforación duodenal por prótesis biliar endoscópica.

Endoscopic biliary drainage through endoscopic retrograde cholangiopancreatography (ERCP) is a widely accepted therapeutic option in malignant biliary obstructions. However, the procedure is not free of complications. Perforation is one possible complication although it is much less frequent (less than 1%) than pancreatitis (5.4%) or hemorrhage (2%). We present 2 cases of duodenal perforation after placement of a biliary prosthesis through ERCP. Both patients had extensive hilar cholangiocarcinoma. Onset of symptoms of perforation occurred a few hours after placement of the prosthesis and the diagnosis was confirmed by computed tomography and laparotomy. We believe that the mechanism through which perforation occurred was proximal adhesion of the prosthesis to the tumor. This increased the intensity of distal trauma produced by the intraduodenal segment, preventing adaptation of the prosthesis to intestinal peristalsis. A good preventive measure would consist of correctly adjusting the length of the prosthesis in relation to the proximal end of the biliary stenosis.

Municipal distribution and trends in bladder cancer incidence in health area of León, Spain (1996-2010).

OBJECTIVE: Spain is a country where bladder cancer incidence and mortality rates are some of the highest in the world. The aim of this study is to know the incidence, trends and geographical distribution of bladder cancer in the health area of León. MATERIAL AND METHODS: the new cases of bladder cancer (CIE-188) in patients residing in the health area of León and registered in the Hospital Tumor Registry of the Centro Asistencial Universitario in León (Spain) between 1996-2010 were included in this study. Triennial crude incidence and adjusted incidence rates to the worldwide and European population were calculated. Population data of the municipalities of Leon (Spain) were obtained from National Institute of Statistic of Spain (INE, Instituto Nacional de Estadística). Data were disaggregated by sex-groups and five-year age groups. Spatial distribution of smoothed municipal relative risks (RR) of bladder cancer was carried out using a Besag, York and Mollié model. Bayesian model were used to calculate the posterior probability (PP) of RR greater than one. RESULTS: 1.573 cases were included. Incidence rates standardized to European population increased among men from 20,8/100.000 (1996-98) to 33,1/100.000 (2006-2008) and among women these rates increased from 1,9/100.000 to 5,9/100.000 for the same period of time. No relevant differences were found in the municipal distribution of the incidences. CONCLUSIONS: bladder cancer incidence rates are high in the European context. Rising trends in incidence in both sexs, particularly in women are observed.

Improved LC method to determine ivermectin in plasma.

A simple, rapid and sensitive high-performance liquid chromatographic (HPLC) method has been developed to quantify Ivermectin (IVM) in plasma using an isocratic system with fluorescence detection. The method included a fast liquid phase extraction using cold methanol. HPLC separation was carried out by reversed phase chromatography with a mobile phase composed of methanol:acetonitrile:water with 0.2% acetic acid (45:50:5 v/v/v), pumped at flow rate of 2 ml min(-1). Fluorescence detection was performed at 365 nm (excitation) and 475 nm (emission). The calibration curve for IVM was linear from 0.25 to 100 ng ml(-1). The validation method yielded good results regarding linearity, precision, accuracy, specificity and recoveries. The values of the limit of detection (LOD) and limit of quantification (LOQ) were 0.032 and 0.167 ng ml(-1), respectively.

Effect of clotrimazole on microsomal metabolism and pharmacokinetics of albendazole.

Albendazole is a broad spectrum anthelmintic drug widely used in human and veterinary medicine. Intestinal and hepatic albendazole metabolism leads to albendazole sulfoxide (active metabolite) and albendazole sulfone (inactive metabolite) formation. Microsomal sulfonase activity can be abolished by in-vitro interaction with clotrimazole and pharmacokinetic studies confirm this interaction. After albendazole incubation, albendazole sulfone formation was completely inhibited by 50 microM clotrimazole in intestinal incubations and a 50% inhibition was observed in hepatic incubations. The lower inhibition constant (K(i)) value observed in the intestinal incubations (9.4 +/- 1.0 microM) compared with the hepatic counterparts (23.3 +/- 15.8 microM) pointed to a greater affinity of the enzymatic systems in the intestine. Regarding the formation of albendazole sulfoxide, an inhibition close to 50% was observed in liver and intestine at 10 microM clotrimazole. The pharmacokinetic parameters obtained following the oral co-administration of albendazole sulfoxide and clotrimazole corroborated the in-vitro inhibition of albendazole sulfone formation, since the ratio of the area under the plasma concentration-time curves for the sulfoxide/sulfone (AUC(ABZSO)/AUC(ABZSO2)) was significantly higher (38.1%). In addition, the AUC and C(max) for albendazole sulfone were significantly lower. The effect of clotrimazole was also studied after prolonged treatment. Hepatic microsomal metabolism of albendazole was induced after 10 days of clotrimazole administration, with significant increases in formation of albendazole sulfoxide (40%) and sulfone (27%). These results offer further insight into the metabolism of benzimidazole drugs and highlight the difficulty involved in human therapy with these anthelmintics, since after prolonged treatment the drug interactions are affected differentially.

[Prevention of recurrence of acute biliary pancreatitis by endoscopic sphincterotomy]. / Prevención de la recidiva de la pancreatitis aguda biliar mediante esfinterotomía endoscópica.

The aim of this study was to know if endoscopic sphincterectomy could be an alternative to cholecystectomy in high surgical risk patients that have suffered acute biliary pancreatitis. Between January 1992 to December 1995 endoscopic sphincterectomy was carried out in 52 high surgical risk patients who had suffered an episode of acute biliary pancreatitis. The lithiasic gallbladder was not removed. The mean age was 75.6 years (35-91). After a follow up of 15.9 months (1-46.5), no patient suffered from a new episode of acute pancreatitis. Six patients (12%) required cholecystectomy due to complications derived from the lithiasic gallbladder. Endoscopic sphincterectomy is an effective alternative to cholecystectomy in the prevention of new episodes of acute biliary pancreatitis in patients with lithiasic gallbladder and high surgical risk. The complications of the lithiasic gallbladder in situ after endoscopic sphincterectomy are relatively infrequent.

Hematopoietic cell transplantation in older patients with hematologic malignancies: replacing high-dose cytotoxic therapy with graft-versus-tumor effects.

Toxicities have limited the use of allogeneic hematopoietic cell transplantation (HCT) to younger, medically fit patients. In a canine HCT model, a combination of postgrafting mycophenolate mofetil (MMF) and cyclosporine (CSP) allowed stable allogeneic engraftment after minimally toxic conditioning with low-dose (200 cGy) total-body irradiation (TBI). These findings, together with the known antitumor effects of donor leukocyte infusions (DLIs), led to the design of this trial. Forty-five patients (median age 56 years) with hematologic malignancies, HLA-identical sibling donors, and relative contraindications to conventional HCT were treated. Immunosuppression involved TBI of 200 cGy before and CSP/MMF after HCT. DLIs were given after HCT for persistent malignancy, mixed chimerism, or both. Regimen toxicities and myelosuppression were mild, allowing 53% of eligible patients to have entirely outpatient transplantations. Nonfatal graft rejection occurred in 20% of patients. Grades II to III acute graft-versus-host disease (GVHD) occurred in 47% of patients with sustained engraftment. With median follow-up of 417 days, survival was 66.7%, nonrelapse mortality 6.7%, and relapse mortality 26.7%. Fifty-three percent of patients with sustained engraftment were in complete remission, including 8 with molecular remissions. This novel allografting approach, based on the use of postgrafting immunosuppression to control graft rejection and GVHD, has dramatically reduced the acute toxicities of allografting. HCT with the induction of potent graft-versus-tumor effects can be performed in previously ineligible patients, largely in an outpatient setting. Future protocol modifications should reduce rejection and GVHD, thereby facilitating studies of allogeneic immunotherapy for a variety of malignancies. (Blood. 2001;97:3390-3400)