Chronic exposure to cannabinoids during adolescence causes long-lasting behavioral deficits in adult mice.

Regular use of marijuana during adolescence enhances the risk of long-lasting neurobiological changes in adulthood. The present study was aimed at assessing the effect of long-term administration of the synthetic cannabinoid WIN55212.2 during adolescence in young adult mice. Adolescent mice aged 5 weeks were subjected daily to the pharmacological action of WIN55212.2 for 3 weeks and were then left undisturbed in their home cage for a 5-week period and finally evaluated by behavioral testing. Mice that received the drug during adolescence showed memory impairment in the Morris water maze, as well as a dose-dependent memory impairment in fear conditioning. In addition, the administration of 3 mg/kg WIN55212.2 in adolescence increased adult hippocampal AEA levels and promoted DNA hypermethylation at the intragenic region of the intracellular signaling modulator Rgs7, which was accompanied by a lower rate of mRNA transcription of this gene, suggesting a potential causal relation. Although the concrete mechanisms underlying the behavioral observations remain to be elucidated, we demonstrate that long-term administration of 3 mg/kg of WIN during adolescence leads to increased endocannabinoid levels and altered Rgs7 expression in adulthood and establish a potential link to epigenetic changes.

Carbohydrate-based polyesters made from bicyclic acetalized galactaric acid.

The dimethyl ester of 2,3:4,5-di-O-methylene-galactaric acid (Galx) was made to react in the melt with 1,n-alkanediols HO(CH(2))(n)OH containing even numbers of methylenes (n from 6 to 12) to produce linear polycyclic polyesters. Two sets of poly(alkylene 2,3:4,5-di-O-methylene-galactarate) polyesters (PE-nGalx) with weight-average molecular weights in the ∼ 5000-10000 and ∼ 35000-45000 ranges were obtained using TBT and DBTO catalysts, respectively. For comparative purposes a set of poly(alkylene adipate) polyesters (PE-nAd) was also synthesized with molecular weights in the higher range using a similar procedure. The thermal stability of PE-nGalx was greater than that of PE-nAd although it notably decayed as molecular weight decreased. The replacement of Ad by Galx in the polyesters caused increases in T(g) of up to 70 °C, and almost doubled the tensile mechanical parameters. All PE-nGalx were semicrystalline but only those made from 1,12-dodecanediol were able to crystallize from the melt with a crystallization rate that diminished as the molecular weight increased. In general, the galactarate containing polyesters displayed higher solubility and wettability than polyadipates, they hydrolyzed faster and exhibited comparable sensitivity to the action of lipases.

[Proposals by the Spanish Society of Quality in Healthcare (SECA) for the recovery of the National Health Service after the COVID-19 pandemic]. / Propuestas de la SECA para la recuperación del Sistema Nacional de Salud tras la pandemia por SARS-CoV-2.

BACKGROUND: The SARS-CoV-2 pandemic has demanded responses for which the National Health System (NHS) was not prepared. The Spanish Society for Quality in Healthcare (SECA) has the mission of promoting quality in healthcare and contributing to its proper functioning. OBJECTIVE: To present SECA recommendations to ensure the quality and safety of patients in the recovery of the NHS following the impact of the SARS-CoV-2 pandemic and the possibility of a resurgence. METHODS: Qualitative study to seek consensus with the participation of 49 representatives of the different stakeholders (patients, managers, professionals, academics and researchers). The areas to be explored were: lessons learned, management of new care demands from COVID-19 patients, recompositing of templates, strengthening the resilience of professionals, new role of patients and contingency plans. RESULTS: Four hundred and twenty-eight proposals were submitted. Once duplicates were deleted and similar proposals were merged, their number was reduced to 120. Of these, 60 proposals were prioritized and grouped into two categories of measures: (1) to recover the Health System (equity, accessibility, effectiveness, efficiency, safety, patient experience and work morale) and (2) to deal with possible outbreaks. CONCLUSION: SECA responds to its commitment to society with recommendations to ensure quality of healthcare and patient safety in the COVID-19 Era.

Difficult airway in a patient with lymphoma. A case report.

A 86-year-old male patient, diagnosed with lymphoma, was scheduled for a submaxillectomy to choose his best chemotherapy treatment. He referred recent voice changes and laterocervical adenopathies without respiratory symptoms. There were no additional risk predictors in preoperative airway assessment. Following anaesthesic induction, an upper airway obstruction occurred. After that, an unexpected difficult airway was encountered. Both clinical situations resulted in unpredicted difficult airway management. Image tests seen after the procedure revealed a severe narrowing of parapharyngeal space due to Waldeyer's ring hypertrophy. This medical condition had remained unnoticed in preoperative assessment. Advanced lymphoproliferative syndromes cause disseminated adenopathies whose parapharyngeal involvement can lead to a difficult airway even in the absence of preoperative risk predictors.

Difficult airway in a patient with lymphoma. A case report. / Vía aérea difícil en paciente con linfoma. Descripción de un caso clínico.

A 86-year-old male patient, diagnosed with lymphoma, was scheduled for a submaxillectomy to choose his best chemotherapy treatment. He referred recent voice changes and laterocervical adenopathies without respiratory symptoms. There were no additional risk predictors in preoperative airway assessment. Following anaesthesic induction, an upper airway obstruction occurred. After that, an unexpected difficult airway was encountered. Both clinical situations resulted in unpredicted difficult airway management. Image tests seen after the procedure revealed a severe narrowing of parapharyngeal space due to Waldeyer's ring hypertrophy. This medical condition had remained unnoticed in preoperative assessment. Advanced lymphoproliferative syndromes cause disseminated adenopathies whose parapharyngeal involvement can lead to a difficult airway even in the absence of preoperative risk predictors.

[Primary care specific scorecards as management tools]. / Cuadros de mando específicos de atención primaria como herramienta de gestión.

INTRODUCTION: Specific Scorecards are a key element to improve strategic lines aimed at enhancing intermediate health outcomes. Their implementation, involving professionals, requires identifying indicators linked to the outcomes of healthcare actions that the scientific literature may endorse. In addition, the inclusion of objectives that can be defined by parameterized by indicators of intermediate results in the health centre program contract, conveys the relevance of health actions and their impact on health. OBJECTIVE: To describe the design, development and outcomes of the specific scorecards of indicators of intermediate health outcomes in the Primary Care information system (eSOAP) in order to promote the involvement of professionals in strategic management from clinical management. METHODS: Phase 1: description of the process (preparation and publication of 147 indicators, 46 of them of chronicity). Phase 2: observational descriptive study on the use of professionals and managers and data on the intermediate health outcomes obtained. RESULTS: A total of 268,849 reports were generated in 2017, with 35,835 reports of specific balanced scorecard (20%) being downloaded in just 6 months. One-quarter (25%) of the indicators of the Centre program contract are intermediate results. The percentage of diabetic patients controlled was 39.2%, and has improved significantly (P<.05) in 5 years. DISCUSSION: The specific scorecards with indicators of intermediate outcomes linked to strategic lines and their inclusion in the program contracts enables professionals to become involved in clinical and strategic management and improves the decision making of professionals and managers.

[Spontaneous closure of full thickness traumatic macular holes]. / Cierre espontáneo de agujeros maculares traumáticos de espesor completo.

CASE REPORT: We present case reports of two young patients suffering from full thickness traumatic macular holes resulting in visual impairment of more than 60%. Both showed anatomical and visual improvement whilst waiting for surgical treatment. DISCUSSION: Spontaneous closure of a traumatic macular hole is an unusual outcome. OCT and clinical follow up enabled monitoring of this resolution during a period of a few weeks. Complex surgery was thus avoided by a short observational period.

[A pilot health care programme for patients with migraine by means of a telemedicine-teleconsultation system in daily clinical practice]. / Programa piloto de atencion a pacientes con migrana a traves de un sistema de telemedicina-teleconsulta en la practica clinica diaria.

INTRODUCTION: Migraine is a very frequent pathology that affects young people; it is a common reason for visits to Neurology outpatient services and a burden on health care services. In Extremadura it causes important movements due to the geographical dispersion that exists in the region. AIM: To present a health care system for patients with migraine in which both primary care and Neurology services work together using the new technologies. PATIENTS AND METHODS: Real time teleconsultation for patients with migraine who need neurological care, by contacting primary care centres that are more than 50 km away from the referral hospital. RESULTS: One year after the system started operating, 13 teleconsultations have been made, with a total of 41 patients being evaluated, 78% of whom were females. The reasons for seeking neurological care were: treatment was not effective (51%), confirmation of diagnosis (22%), change in the clinical features (17.1%), increased frequency or intensity of seizures (5%), onset of migraine (2.4%) and not specified (17%). The neurologist conducted a structured interview, with the aid of the primary care team, and a clinical report was drawn up with a proposal for treatment following the usual clinical praxis. Cases that did not fit the protocol were referred to the traditional model of care. CONCLUSIONS: A programme that is developed in accordance with the first level of health care for these patients, by means of a telematic system, allows them to be evaluated without the need to travel to a hospital and favours the relationship between the two levels of health care.

The BET/BRD inhibitor JQ1 improves brain plasticity in WT and APP mice.

Histone acetylation is essential for memory formation and its deregulation contributes to the pathogenesis of Alzheimer's disease. Thus, targeting histone acetylation is discussed as a novel approach to treat dementia. The histone acetylation landscape is shaped by chromatin writer and eraser proteins, while readers link chromatin state to cellular function. Chromatin readers emerged novel drug targets in cancer research but little is known about the manipulation of readers in the adult brain. Here we tested the effect of JQ1-a small-molecule inhibitor of the chromatin readers BRD2, BRD3, BRD4 and BRDT-on brain function and show that JQ1 is able to enhance cognitive performance and long-term potentiation in wild-type animals and in a mouse model for Alzheimer's disease. Systemic administration of JQ1 elicited a hippocampal gene expression program that is associated with ion channel activity, transcription and DNA repair. Our findings suggest that JQ1 could be used as a therapy against dementia and should be further tested in the context of learning and memory.

[Development and evolution of a balanced scorecard in primary health care: Lessons learned]. / Desarrollo y evolución de un cuadro de mando integral en atención primaria: lecciones aprendidas.

OBJECTIVES: To describe the design, implementation, and monitoring of eSOAP (Primary Health Care Balanced Scorecard) and its role in the deployment of strategic objectives and clinical management, as well as to show the lessons learned during six years of follow-up. METHOD: Descriptive study areas: methodology (conceptual framework, strategic matrix, strategic map, and processes map), technology and standardisation. RESULTS: As of December 2014, 9,046 (78%) professionals are registered in eSOAP. A total of 381 indicators were measured from 16 data sources, of which 36% were of results (EFQM model), 39.1% of clinical management, and 20% were included in the Program Centre Contract. The Balanced Scorecard has enabled to deploy all strategic lines of Primary Health Care, and has enabled the healthcare professionals to evaluate the evolution of results over time, and at patient level (e.g. 16% increase in control of diabetic patients). A total of 295,779 reports were generated and 13,080 professionals were evaluated by goals. CONCLUSIONS: There was an increased use of the eSOAP application by the professionals. The Balanced Scorecard was the key in deploying Primary Health Care strategies. It has helped clinical management and improved relevant indicators (health, patient experience, and costs), such as the management models that we used as references (EFQM Kaplan and Norton), and new emerging scenarios (Triple aim).

Dietary intake of fiber and decreased risk of cancers of the colon and rectum: evidence from the combined analysis of 13 case-control studies.

BACKGROUND: Colorectal cancer is a major public health problem in both North America and western Europe, and incidence and mortality rates are rapidly increasing in many previously low-risk countries. It has been hypothesized that increased intakes of fiber, vitamin C, and beta carotene could decrease the risk of colorectal cancer. PURPOSE: The objective of this study was to examine the effects of fiber, vitamin C, and beta-carotene intakes on colorectal cancer risk in a combined analysis of data from 13 case-control studies previously conducted in populations with differing colorectal cancer rates and dietary practices. The study was designed to estimate risks in the pooled data, to test the consistency of the associations across the studies, and to examine interactions of the effects of the nutrients with cancer site, sex, and age. METHODS: Original data records for 5287 case subjects with colorectal cancer and 10,470 control subjects without disease were combined. Logistic regression analysis was used to estimate relative risks and confidence intervals for intakes of fiber, vitamin C, and beta carotene, with the effects of study, sex, and age group being adjusted by stratification. RESULTS: Risk decreased as fiber intake increased; relative risks were 0.79, 0.69, 0.63, and 0.53 for the four highest quintiles of intake compared with the lowest quintile (trend, P < .0001). The inverse association with fiber is seen in 12 of the 13 studies and is similar in magnitude for left- and right-sided colon and rectal cancers, for men and for women, and for different age groups. In contrast, after adjustment for fiber intake, only weak inverse associations are seen for the intakes of vitamin C and beta carotene. CONCLUSION: This analysis provides substantive evidence that intake of fiber-rich foods is inversely related to risk of cancers of both the colon and rectum. IMPLICATIONS: If causality is assumed, we estimate that risk of colorectal cancer in the U.S. population could be reduced about 31% (50,000 cases annually) by an average increase in fiber intake from food sources of about 13 g/d, corresponding to an average increase of about 70%.

[Influence of tumor location in patients with breast cancer on the sentinel node detection]. / Influencia de la localización del cáncer de mama en la detección del ganglio centinela.

OBJECTIVE: To evaluate the influence of tumour quadrant localization on the sentinel node (SN) detection and the visualisation of internal mammary chain (IM) drainage by radioisotopic techniques. 316 patients with breast cancer were studied. Mean age 57 years (range 29-88). All patients received 37-74 MBq of 99mTc-albumin nanocolloid in 2 ml by peritumoral injection. The breast cancer was located in the upper outer quadrant in 189 patients, in the upper inner in 57, in the lower outer in 57, in the lower inner in 55 and in the subareolar area in 18 patients. At two hours p.i., anterior and lateral chest lymphographies were obtained. The SN location was marked on the patient skin with permanent ink. SN was identified intraoperatively by the gamma probe. Histopatological analysis included imprints, delayed hematoxilin-eosin, inmunohistochemistry CAM 19-2 and PCR. RESULTS: The scintigraphy and surgical detection was in the upper outer quadrant of 90 % and 93 % respectively; in the lower outer quadrant of 91 % and 95 %, in the upper inner quadrant of 93 % and 95 %, in the lower inner quadrant 87 % and 95 % and in the subareolar area in 94 % and 83 %. The IM chain drainage was of 6 % in the UO, in the LO of 5 %, in the UI of 12 %, in the LI of 20 % and none in subareolar. CONCLUSIONS: Our data suggest that sentinel node location (quadrant) is not a influential factor in the scintigraphy and surgical detection. Tumours localised in internal quadrant show a higher rate of IM chain drainage.

Occurrence of Ki-ras and p53 mutations in primary colorectal tumors.

Twenty-four colorectal tumors and their paired mucosa were examined for allele loss on chromosomes 5 and 17, using polymerase chain reaction-amplified DNA, and for mutations in the Ki-ras and p53 genes. In addition, 19 benign polyps were analysed for mutations in the p53 gene. RFLP analysis of the long arm of chromosome 5 indicated an allele loss frequency of 47% for malignant tumors, a value somewhat higher than previously observed. Examination of the short arm of chromosome 17 indicated an allele loss of 60%. Sequence analysis of the p53 gene in colorectal tumors indicated that 64% contained a mutation. All tumors showing allele loss on chromosome 17 were mutant for p53, suggesting that mutation of one p53 allele precedes the hemizygotic loss of the wild-type allele. Sequence analysis of the p53 gene in 19 benign polyps, devoid of severe dysplasia, did not reveal any mutants, suggesting that the mutation of one p53 allele is an event that takes place after polyp formation. Ki-ras mutations were observed in 48% of the tumors examined. All tumors which were mutant for Ki-ras, except for one, were also mutant for p53.

Effect of Escherichia coli lipopolysaccharide on surfactant secretion in primary cultures of rat type II pneumocytes.

The purpose of this study is to evaluate the effect of the Escherichia coli lipopolysaccharide on the secretion of phosphatidylcholine, the principal component of pulmonary surfactant, in primary cultures of rat alveolar type II pneumocytes. Lipopolysaccharide stimulated phosphatidylcholine secretion in a time- and dose-dependent manner. At a concentration of 200 micrograms/ml, lipopolysaccharide stimulated the release of phosphatidylcholine 4-fold over the basal secretory rate, and the concentration producing half the maximal response was 20 micrograms/ml. The stimulatory effect of lipopolysaccharide on phosphatidylcholine secretion was additive to that of the protein kinase C activator TPA, which is a potent stimulator of surfactant secretion. Lipopolysaccharide did not activate protein kinase C, which suggests that stimulation of phosphatidylcholine secretion by the endotoxin was through a mechanism independent of protein kinase C activation.

Isolation of AmphiCASP-3/7, an ancestral caspase from amphioxus (Branchiostoma floridae). Evolutionary considerations for vertebrate caspases.

Caspases are a large family of cysteine proteases that play an essential role as effectors of apoptosis in metazoans. Thirteen different caspases have been identified in vertebrates so far, and their function in apoptotic or inflammatory responses is well documented. We have taken advantage of the broadly accepted condition of amphioxus (Cephalochordata, Branchiostoma floridae) as the closest living relative to vertebrates to study the molecular evolution of caspases. Here we report for the first time the pattern of programmed cell death during development of cephalochordates. We also describe the isolation and functional characterisation of the first caspase related gene in amphioxus, which we named AmphiCASP-3/7. The amphioxus caspase is expressed throughout development, from the gastrula to larva stage. AmphiCASP-3/7 induced cell death when ectopically expressed in human HEK 293T cells, and the recombinant protein was inhibited by DEVD peptides. AmphiCASP-3/7 reflects the primitive condition of the executor vertebrates caspases -3 and -7, prior to vertebrate specific duplication. Interestingly, AmphiCASP-3/7 is functionally closer to vertebrate caspase-7, as shown by substrate specificity both in vitro and in MCF7 cells. Our phylogenetic and functional data help in drawing the evolutionary history of caspases, and illustrates an example of acquisition in vertebrates of novel functional properties after gene duplication.

[Simultaneous location of non-palpable breast neoplasms and sentinel node (SN) study by radioisotopic techniques]. / Localización simultánea de neoplasias de mama no palpables y estudio del ganglio centinela (GC) mediante técnicas radioisotópicas.

OBJECTIVE: To obtain correct location of non-palpable breast lesions, with high suspicion of malignancy and detection of SN by radiosotopic techniques. MATERIAL AND METHODS: Thirty-one patients whose ages ranged from 35 to 79 years, with non-palpable breast lesions detected by mammography and/or ultrasonography were studied. All the patients were diagnosed of breast cancer and treated with primary chemotherapy. All the patients underwent total axillary dissection. At 24 hours of the intervention, all patients received one dose of 37 MBq (1 mCi) of 99mTc labeled macroaggregated albumin (MAA) in the center of the lesion by ultrasonographic guide. Scintigraphic images were performed in anterior and lateral projections (in prone decubitus with hanging breast) to verify the correct location of the radiopharmaceutical. After, a study of the SN was performed by subdermal administration of an 18 MBq (0.5 mCi) dose of 99mTc labeled nanocolloid. The SN site was labeled on the skin with indelible ink. The intrasurgical site of the breast lesion and SN was performed using a gamma detector probe. Correct placement of the intralesional radiopharmaceutical, existence of disease free borders and histological study of SN were performed by the pathologist in the surgical act. The differed pathology study was performed with hematoxilin-eosin and immunohistochemistry. RESULT: In 29 of the 31 lesion sites, there was good placement of the radiotracer (93.5 %). There was 1 case of contamination of the needle pathway and another that did not coincide with the lesion, due to poor placement. Location of the SN was 96 % in the axilla and 4 % in axilla and internal mammary chain. The SN was located in surgery in 28/31 patients (90 %). CONCLUSION: Simultaneous radioguided location of the hidden breast lesions and sentinel node is a simple method, which is well tolerated by the patients and can be done in a single operation act.

Glucagon-like peptide-1-(7-36)amide increases pulmonary surfactant secretion through a cyclic adenosine 3',5'-monophosphate-dependent protein kinase mechanism in rat type II pneumocytes.

Glucagon-like peptide-1 (GLP-1) receptor messenger RNA has been identified in cells considered type II pneumocytes that are involved in the synthesis and secretion of the pulmonary surfactant. In an attempt to open new insights into the control of surfactant secretion, we studied the effects of glucagon-related peptides in this process. Accordingly, type II pneumocytes were isolated from Wistar rat lungs and cultured overnight with [methyl-14C]choline, and then the basal and stimulated secretions of [14C]phosphatidylcholine were measured. GLP-1(7-36)amide stimulated phosphatidylcholine secretion in a concentration-dependent manner in the 1-100 nM range; the concentration of the peptide that produced a half-maximal response was 10 nM. Exendin-4 induced similar effects. No changes were observed when GLP-1-(1-37), GLP-2, or exendin-(9-39) was added to the medium. However, the latter reversed the stimulatory effects of GLP-1-(7-36)amide and exendin-4. A study of the mechanism through which GLP-1-(7-36)amide exerts its stimulatory effect was carried out using different agents that are well known stimulants of phosphatidylcholine secretion. GLP-1-(7-36)amide did not produce any change in the stimulatory effect observed with terbutaline or 8-bromo-cAMP, suggesting the involvement of a cAMP-dependent protein kinase in the stimulatory effect of this peptide on phosphatidylcholine secretion. It was further supported by the use of inhibitors of protein kinases and by the stimulation of cAMP production in type II pneumocytes incubated with either GLP-1-(7-36)amide or exendin-4.

Cloning and sequence analysis of the Mucor circinelloides pyrG gene encoding orotidine-5'-monophosphate decarboxylase: use of pyrG for homologous transformation.

A 3.2-kb BamHI genomic DNA fragment containing the pyrG gene of Mucor circinelloides was isolated by heterologous hybridization using a pyrG cDNA clone of Phycomyces blakesleeanus as the probe. The complete nucleotide sequence of the M. circinelloides pyrG gene encoding orotidine-5'-monophosphate decarboxylase (OMPD) was determined and the transcription start points (tsp) were mapped by primer extension analysis. The predicted amino acid sequence showed homology with the OMPD sequences reported from other filamentous fungi, with 96% similarity with the OMPD of P. blakesleeanus. Analysis of the sequence revealed the presence of two short introns whose length and location were confirmed by sequencing a cDNA clone and comparing this with its genomic counterpart. The intron splice sites and the 5'- and 3'-noncoding flanking regions show general features of fungal genes. Northern-blot hybridization revealed the pyrG transcript to be approx. 1.0 kb. The M. circinelloides pyrG cDNA clone was able to complement the pyrF::Mu-1 mutation of Escherichia coli when inserted between bacterial expression signals. Additionally, the genomic clone complemented the M. circinelloides pyrG4 mutation. When an M. circinelloides autonomous replication sequence was included in the transforming plasmid, the average transformation frequency obtained was 600 to 800 transformants per micrograms DNA and per 10(6) viable protoplasts.