Cross-sectional survey on awareness of colorectal cancer and a screening programme for primary health care professionals in Catalonia, Spain.

This study aimed to assess whether primary health care professionals have accurate information regarding colorectal cancer (CRC) screening procedures, surveillance recommendations and referral strategies. This cross-sectional descriptive study was based on a survey conducted among primary health care professionals in Barcelona, Spain. The questionnaire was used to gather information regarding CRC screening procedures as well as demographic and professional characteristics of the study subjects. A CRC and screening awareness score (ranging from 0 to 12) was created based on the survey questions. The response rate was 58.9% (206/305). The estimated mean score (standard deviation) was 8.43 (SD: 1.30). For four questions, more than 60% of the answers were incorrect: one related to risk factors, two concerning follow-up colonoscopy, and one related to surveillance. Only 30.8% of the participants believed that they were responsible for determining the appropriate surveillance intervals and for scheduling colonoscopies. Although the professionals had sufficient knowledge of CRC screening, professional knowledge of some aspects related to the major non-modifiable risk factors for the disease and surveillance colonoscopy procedures could be improved. Frequent communication with professionals is necessary to maintain updated screening-related information. Possible methods for facilitating communication could include continuous briefings, regular message reminders or educational websites.

[Retrospective observational study of the persistence of SARS-CoV-2 infection in patients previously treated with rituximab]. / Estudio observacional retrospectivo de persistencia de infección por SARS-CoV-2 en pacientes tratados previamente con rituximab.

OBJECTIVE: Rituximab-induced immunosuppression could be a risk factor for mortality from COVID-19. The aim of the study was to describe the prevalence of SARS-CoV-2 infection in patients who have received rituximab and its association with a persistent viral infection. METHODS: Retrospective observational study of patients who received rituximab in the 6 months before to the onset of the pandemic. We analyzed the presence of infection and associated them with demographic variables, pathological history related to an increased risk of developing severe COVID-19, the doses of rituximab received, the type of ventilatory support, thromboembolic events, and the treatment received. A descriptive analysis of all the variables was carried out and infected and uninfected patients were compared. RESULTS: We screened a total of 68 patients who had received rituximab (median cumulative dose: 4,161mg (2,611-8,187.5)). 54.4% men, mean age 60.8 years (15.7; 25-87)). C + was confirmed for 22 patients. Of these, 45.5% had high blood pressure, 36.4% Diabetes Mellitus, 31.8% smokers/ex-smoker, 22.7% lung disease, 13.6% heart disease and 4.5% obesity. There were no statistically significant differences between C+ and C-. Only 2 patients developed immunity. For 10 patients (45.5%) did not have a negative CRP until the end of the follow-up. There was no association with cumulative dose of rituximab. The mortality rate was 22.7% in the C+. CONCLUSIONS: We observe that the persistence of the infection leads to a worse evolution of COVID-19. The use of alternatives should be considered during the pandemic, because of patients with decreased B-cell function may have high risk of fatal progression from COVID-19.

Molecular analysis of 30 Niemann-Pick type C patients from Spain.

Mutations in the NPC1 or NPC2 gene are responsible for Niemann-Pick type C (NPC) disease (OMIM #257220), an autosomal recessive neurodegenerative lysosomal storage disorder caused by an incorrect regulation of intracellular lipid trafficking. A molecular analysis carried out in 30 unrelated patients identified 43 distinct mutations in the NPC1 gene, 12 of which had not been previously described. The novel NPC1 alleles were four amino acid substitutions (p.F995L, p.F1079S, p.L1106P and p.G1209E), a nonsense mutation (p.E1089X), a 1-bp insertion (p.L1117PfsX4), an in-frame deletion (p.N916del), four intronic changes (c.58-3280C>G, c.882-28A>T, c.2604+5G>A and c.3591+5G>A) that affect the splicing mechanism, and the first deletion including the whole gene described in NPC disease. In all the splice site mutations, the formation of abnormal spliced transcripts was confirmed by cDNA analysis, and mRNA degradation by the nonsense-mediated mRNA decay process was also assessed. As it has been previously reported in this disease, genotype-phenotype correlations are limited due to the large number of private mutations. We describe for the first time one homozygous patient for p.I1061T mutation, who presented the severe infantile clinical onset, and another patient with the variant biochemical phenotype, whose clinical presentation was the neonatal form of the disease.

Response to creatine analogs in fibroblasts and patients with creatine transporter deficiency.

Creatine transporter (CRTR) deficiency is one of the most frequent causes of X-linked mental retardation. The lack of an effective treatment for this disease, in contrast to creatine (Cr) biosynthesis disorders that respond to Cr monohydrate (CM), led us to analyze the efficacy of a lipophilic molecule derived from Cr, creatine ethyl ester (CEE), in fibroblasts and patients with CRTR deficiency. CM and CEE uptake studies were performed in six controls and four fibroblast cell lines from patients. We found a significant increase in Cr uptake after 72 h of incubation with CEE (500 micromol/L) in patients and control fibroblasts compared to incubation with CM. Subsequently, we assayed the clinical effect of CEE administration in four patients with CRTR deficiency. After 1 year of treatment, a lack of significant improvement in neuropsychological assessment or changes in Cr level in brain (1)H MRS was observed, and CEE was discontinued. In conclusion, this 12-month trial with CEE did not increase the brain concentration of Cr. Our in vitro data lend support to the idea of a certain passive transport of CEE in both pathological and control cells, although more lipophilic molecules or other cell systems that mimic the BBB should be used for a better approach to the in vivo system.

Mutational study in the PDHA1 gene of 40 patients suspected of pyruvate dehydrogenase complex deficiency.

We screened for PDHA1 mutations in 40 patients with biochemically demonstrated PDHc deficiency or strong clinical suspicion, and found changes with probable pathological significance in 20. Five patients presented new mutations: p.A169V, c.932_938del, c.1143_1144 ins24, c.1146_1159dup and c.510-30G> A, this latter is a new undescribed cause of exon 6 skipping. Another four mutations have been found, and previously reported, in our patients: p.H113D, p.P172L, p.Y243del and p.Y369Q. Eleven patients presented seven known mutations: p.R127Q, p.I166I, p.A198T, p.R263G, p.R302C, p.R378C and c.1142_1145dup. The latter three were found in more than one unrelated patient: p.R302C was detected in a heterozygous girl and a mosaic male, p.R378C in two males and finally, c.1142_1145dup in three females; only one in 20 mothers was found to be a carrier (p.R263G). Apart from those 20 patients, the only alteration detected in one girl with clear PDHc and PDH-E1 deficiency was the silent change c.396A> C (p.R132R), and other eight PDHc deficient patients carry combinations of known infrequent polymorphisms that are overrepresented among our 20 unsolved patients. The importance of these changes on PDH activity is unclear. Investigations in the other PDHc genes are in course in order to elucidate the genetic defect in the unresolved patients.

PDH E1ß deficiency with novel mutations in two patients with Leigh syndrome.

Most cases of pyruvate dehydrogenase complex (PDHc) deficiency are attributable to mutations in the PDHA1 gene which encodes the E(1)α subunit, with few cases of mutations in the genes for E(3), E3BP (E(3) binding protein), E(2) and E(1)-phosphatase being reported. Only seven patients with deficiency of the E(1)ß subunit have been described, with mutations in the PDHB gene in six of them. Clinically they presented with a non-specific encephalomyopathy. We report two patients with new mutations in PDHB and Leigh syndrome. Patient 1 was a boy with neonatal onset of hyperlactataemia, corpus callosum hypoplasia and a convulsive encephalopathy. After neurological deterioration, he died at age 5 months. Autopsy revealed the characteristic features of Leigh syndrome. Patient 2, also a boy, presented a milder clinical course. First symptoms were noticed at age 16 months with muscular hypotonia, lactic acidosis and recurrent episodes of somnolence and transient tetraparesis. MRI revealed bilateral signal hyperintensities in the globus pallidus, midbrain and crura cerebri. PDHc and E(1) activities were deficient in fibroblasts in patient 1; in patient 2 PDHc deficiency was found in skeletal muscle. Mutations in PDHA1 were excluded. Sequencing of PDHB revealed a homozygous point mutation (c.302T>C), causing a predicted amino acid change (p.M101T) in patient 1. Patient 2 is compound heterozygote for mutations c.301A>G (p.M101V) and c.313G>A (p.R105Q). All three mutations appear to destabilize the E(1) enzyme with a decrease of both E(1)α and E(1)ß subunits in immunoblot analysis. To our knowledge, these patients with novel PDHB mutations are the first reported with Leigh syndrome.

Searching for a job: Cardiac responses to acute stress and the mediating role of threat appraisal in young people.

Being unemployed and looking for a job has become a source of stress for many people in several European countries. However, little attention has been paid to the impact of this stressful situation on the individuals' psychophysiological stress responses. The aim of this study was to investigate the effect of being an unemployed job seeker on cognitive threat appraisal and cardiac responses to a psychosocial stressor. We exposed a group of unemployed job seekers (N = 42) and a matched group of unemployed non-job seekers (N = 40) to a standardized social stressor in form of job interview, the Trier Social Stress Test. Our results showed that unemployed job seekers manifest lower cardiac responses, along with a lower cognitive threat appraisal, compared to non-job seekers. Moreover, we observed a full mediating role of cognitive threat appraisal on the relationship between being an unemployed job seeker and cardiac responses to stress. These findings reveal that being unemployed and looking for a job has an effect on physiological responses to acute stress, as well as the importance of psychological process related to the situation. These responses might lead to negative health and motivational consequences. Theoretical and practical implications are discussed.

Microstructural changes in Teruel dry-cured ham during processing.

Dry-cured ham, "Protected Designation of Origin (PDO)" Teruel, is a high quality meat product processed using a traditional dry-curing procedure. The objective of this paper was to study the microstructure of the Biceps femoris and Semimembranosus muscles during "PDO Teruel" dry-cured ham processing using electron microscopy techniques (Cryo-SEM, SEM and TEM). The Semimembranosus and Biceps femoris muscles from raw ham show the typical structure of muscle tissue in meat. The muscle fibres appear firmly attached to one another by the endomysial connective tissue; the myofibrils inside the cells are strongly attached to each other and to the sarcolemma. In raw ham, the typical structural elements that constitute the sarcomere can be observed by TEM. Important microstructural changes are observed following salting; reflected in the fact that the Z-disks inside the myofibrils are no longer in line and there is important degradation of the cell membranes in this stage. At the end of the process, an accumulation of solutes, which could be products from proteolysis occurring mainly in the last stage of ripening, could be observed in both muscles. Thus the proteolysis and dehydratation phenomena that take place during "PDO Teruel" dry-cured ham processing occur at an ultrastructural level, and this is the basis to produce a product with the sensory features appreciated by consumers.

Changes in proteins during Teruel dry-cured ham processing.

The aim of this work was to investigate the degradation of the water-soluble and myofibrillar proteins during the production of "PDO Teruel" cured ham using SDS-PAGE, and measurement of proteolytic activities (cathepsins B+L, cathepsin L, cathepsin D), as factors that influence the sensory characteristics of this product. This paper contributes to the specific characterisation of a product included in the European Union list of special quality products. The results showed that water-soluble proteins decrease considerably due to salting out and drainage after salting. The degradation of myofibrillar proteins is more pronounced during the ripening process, particularly in the last four months when the main proteins responsible for the structure of muscular tissue are affected. There is an important residual enzymatic activity for cathepsin B, L and D, which must be a decisive factor in the proteolysis observed during "PDO Teruel" ham processing.

Acute stress and working memory: The role of sex and cognitive stress appraisal.

Sex is considered a moderating factor in the relationship between stress and cognitive performance. However, sex differences and the impact of cognitive stress appraisal on working memory performance have not received much attention. The aim of this study was to investigate the role of physiological responses (heart rate and salivary cortisol) and cognitive stress appraisal in Working Memory (WM) performance in males and females. For this purpose, we subjected a comparable number of healthy young adult males (N=37) and females (N=45) to a modified version of the Trier Social Stress Test (TSST), and we evaluated WM performance before and after the stress task. Females performed better on attention and maintenance after the TSST, but males did not. Moreover, we found that attention and maintenance performance presented a negative relationship with cortisol reactivity in females, but not in males. Nevertheless, we observed that only the females who showed a cortisol decrease after the TSST performed better after the stress task, whereas females and males who showed an increase or no change in cortisol levels, and males who showed a cortisol decrease, did not change their performance over time. In females, we also found that the global indexes of cognitive stress appraisal and cognitive threat appraisal were negatively related to attention and maintenance performance, whereas the Self-concept of Own Competence was positively related to it. However, these relationships were not found in males.

Long-term effects of repeated social stress on the conditioned place preference induced by MDMA in mice.

Previous studies have demonstrated that social defeat stress increases the rewarding effects of psychostimulant drugs such as cocaine and amphetamine. In the present study we evaluated the long-term effects of repeated social defeat (RSD) on the rewarding effects of ±3,4-methylenedioxymethamphetamine (MDMA) hydrochloride in the conditioned place preference (CPP) paradigm. Adolescent and young adult mice were exposed to four episodes of social defeat (on PND 29-40 and PND 47-56, respectively) and were conditioned three weeks later with 1.25 or 10mg/kg i.p. of MDMA (experiment 1). The long-term effects of RSD on anxiety, social behavior and cognitive processes were also evaluated in adult mice (experiment 2). RSD during adolescence enhanced vulnerability to priming-induced reinstatement in animals conditioned with 1.25mg/kg of MDMA and increased the duration of the CPP induced by the 10mg/kg of MDMA. The latter effect was also observed after RSD in young adult mice, as well as an increase in anxiety-like behavior, an alteration in social interaction (reduction in attack and increase in avoidance/flee and defensive/submissive behaviors) and an impairment of maze learning. These results support the idea that RSD stress increases the rewarding effects of MDMA and induces long-term alterations in anxiety, learning and social behavior in adult mice. Thus, exposure to stress may increase the vulnerability of individuals to developing MDMA dependence, which is a factor to be taken into account in relation to the prevention and treatment of this disorder.

Erythrocyte sodium transport, intraplatelet pH, and calcium concentration in salt-sensitive hypertension.

We evaluated changes in erythrocyte sodium transport systems, platelet pH, and calcium concentration induced by low and high salt intakes in a group of 50 essential hypertensive patients classified on the basis of their salt sensitivity. Patients received a standard diet with 20 mmol NaCl daily for 2 weeks supplemented in a single-blind fashion by placebo tablets the first 7 days and NaCl tablets the following 7 days. Salt sensitivity, defined as a significant rise (P <.05) in 24-hour mean blood pressure obtained by ambulatory blood pressure monitoring, was diagnosed in 22 (44%) patients. The remaining 28 (56%) were considered to have salt-resistant hypertension. In the entire group of hypertensive patients, high salt intake promoted a significant increase (P <.05) in the maximal rate of erythrocyte NA(+)-Li(+) countertransport (from 271 +/- 19 to 327 +/- 18 microM/(L cells/h) and of the Na(+)-dependent HCO3(-)-CL(-) exchanger (from 946 +/- 58 to 1237 +/- 92 microM/L cells/h) as well as in platelet pH (from 7.15+/-0 0.01 to 7.19+/-0.02 and calcium concentration (from 49+/-2 to 57 +/-2 nmol/L). Depending on salt sensitivity, high salt intake promoted opposing changes in some of the sodium transport systems studied. Salt-sensitive patients increased the maximal rate of the erythrocyte Na(+)-K(+) pump (fom 7.0 +/- 0.4 to 8.8 +/- 0.4 mmol/(L cells/h), Na(+)-K(+)-Cl(-) cotransport (from 416 +/- 37 to 612 +/- 41 micromol/(L cells/h), Na(+)-Li(+) countertransport (from 248 +/- 20 to 389 +/- 17 micromol/(L cells/h) at the end of the high salt period. Conversely, salt-resistant patients decreased the Na(+)-K(+) pump (from 8.0 +/- 0.4 to 6.9 +/- 0.3 mmol/(L cells/h) and Na(+)-K(+)-Cl(-) cotransport (from 578 +/- 53 to 481 +/- 43 micromol/(L cells/h). We conclude that modulation of erythrocyte sodium transport systems by high salt intake depends on salt sensitivity. The Na(+)-K(+) pump, Na(+)-K(+)-Cl(-) cotransport, and Na(+)-Li(+) countertransport increase in salt-sensitive patients, whereas the activity of these sodium transport systems tends to decrease in salt-resistant patients. Independent of salt sensitivity, high salt intake promotes a significant increase in the erythrocyte Na(+)-dependent HCO3(-)-Cl(-) exchanger, platelet pH, and calcium concentration in essential hypertensive patients.