[Summary PAPPS Childhood and Adolescence 2022]. / Resumen PAPPS Infancia y Adolescencia 2022.

Two important topics about children and adolescents in our primary care activity are presented in this update document: tobacco smoking prevention in adolescence and prophylaxis with vitamin K to prevent the hemorrhagic disease of the newborn.

The Cost of Postoperative Complications and Economic Validation of the Comprehensive Complication Index: Prospective Study.

OBJECTIVE: To validate the Comprehensive Complication Index (CCI) via an assessment of its relation to postoperative costs. BACKGROUND: The CCI summarizes all the postoperative complications graded by the Clavien-Dindo classification (CDC) on a numerical scale. Its relation to hospital costs has not been validated to date. METHODS: Prospective observational cohort study, including all patients undergoing surgery at a general surgery service during the 1-year study period. All complications graded with the CDC and CCI and related to the initial admission, or until discharge if the patient was readmitted within 90 days of surgery, were included. The surgeries were classified according to their Operative Severity Score (OSS) and in 4 groups of homogeneous surgeries. All postoperative costs were recorded. RESULTS: In all, 1850 patients were included, of whom 513 presented complications (27.7%). The CDC and the CCI were moderately to strongly correlated with overall postoperative costs (OPCs) in all OSS groups (rs = 0.444-0.810 vs 0.445-0.820; P < 0.001), homogeneous surgeries (rs = 0.364-0.802 vs 0.364-0.813; P < 0.001), prolongation of postoperative stay (rs = 0.802 vs 0.830; P < 0.001), and initial operating room costs (rs = 0.448 vs 0.451; P < 0.001). This correlation was higher in emergency surgery. With higher CDC grades, the OPC tended to increase an upward trend. In the multivariate analysis, CDC, CCI, age, and duration of surgery were all associated with OPC (P < 0.001). CONCLUSIONS: In our environment, the CCI presented associations with OPC. This demonstration of its economic validity enhances its clinical validity.

[Childhood and adolescence PAPPS summary 2020]. / RESUMEN PAPPS Infancia y Adolescencia 2020.

Four important topics about children and adolescents in our Primary Care activity are presented in this update document: support for breastfeeding, promotion of physical activity, prevention of child injuries due to traffic accidents, and screening for major depression.

Lead exposure in common shelduck (Tadorna tadorna): Tracking the success of the Pb shot ban for hunting in Spanish wetlands.

Levels of lead (Pb) were analyzed in tissues of 25 Common shelduck (Tadorna tadorna) from La Albufera Natural Park (NP) in Valencia (Eastern Spain), which were found dead due to a botulism outbreak. The objective was to assess Pb exposure in waterfowl, fourteen years after the implementation of the Real Decreto 581/2001, which banned the use of Pb ammunition for hunting activities in internationally relevant wetlands. For this purpose, this study measured the actual ingestion of lead pellets in Common shelduck from La Albufera de Valencia and provide data on Pb residue concentrations in different tissues of this species breeding in this NP. The Pb distribution pattern in tissues was bone > kidney > liver > brain > muscle, with Pb concentrations of 778.96 ±â€¯998.64, 122.40 ±â€¯89.18, 92.08 ±â€¯57.65, 18.90 ±â€¯16.30 and 15.13 ±â€¯11.85 ng/g (wet weight), respectively. This work presents, as far as we are aware, the first published data on Pb concentrations in Common shelduck. The Pb levels detected were lower than those reported in other studies on Anatid species from Spanish wetlands, which may be explained by this ban. Moreover, lead concentrations found were below those levels for which any observable effect has been described for acute or chronic lead exposure.

Giant right pulmonary artery aneurysm in a systemic-to-pulmonary artery shunt.

Aneurysms of the pulmonary arteries and trunk are rare entities. The Waterston shunt is a palliative procedure for children with cyanotic CHD due to obstruction of the pulmonary outflow. Described complications are distortion of the pulmonary artery and pulmonary arterial hypertension. We report a patient with a giant right pulmonary artery aneurysm in relation to a Waterston shunt.

The role of tridimensional dynamic ultrasound for pelvic floor evaluation.

INTRODUCTION: Dynamic endoanal ultrasound has emerged in recent years as a test that could replace the now existing tests in the diagnosis of pelvic floor disorders. The aim of this paper is to determine the usefulness of echodefecography in the diagnosis and evaluation of patients with symptoms of anorrectal obstruction, and show the results obtained after its implementation in a pelvic floor unit, as a complementary tool that could replace conventional defecography. METHODS: In this retrospective study we analyzed 66 patients with a mean age of 55 years (19-83), 61 women (92%). All dynamic ultrasound was performed in 3 dimensions and was correlated with symptoms and physical findings in the consultation. A descriptive and inferential study was performed to find a kappa correlation between physical examination and echodefecography. RESULTS: The reasons for consultation were: Anorrectal obstruction syndrome 36 patients (54.5%), pelvic organ prolapse 27 patients (40.9%), and anorrectal obstruction syndrome along with pelvic organ prolapse 3 patients (4.5%). The correlation of the 2 groups indicated that echodefecography diagnosed more patients with grade III rectocele, enteroceles, and anismus than the combination of scan-ultrasound-manometry-proctoscopy (Kappa 0.26, 0.38 and 0.21, 95% CI: from 0,07 to 1.00, 0.15 to 1.00 and from 0.12 to 1.00, respectively) (P<.001). Conversely, echodefecography diagnosed less perineal descense (Kappa 0.28, 95% CI: 0.12 to 1.00). CONCLUSIONS: Dynamic anal ultrasonography may have a role as a complementary test in patients with pelvic floor disorders, achieving diagnoses that would go undetected by inspection, physical examination and manometry.

Field Collection and Laboratory Maintenance of Canopy-Forming Giant Kelp to Facilitate Restoration.

Canopy-forming kelps are essential foundation species, supporting biodiversity and providing ecosystem services valued at more than USD$500 billion annually. The global decline of giant kelp forests due to climate-driven ecological stressors underscores the need for innovative restoration strategies. An emerging restoration technique known as 'green gravel' aims to seed young kelps over large areas without extensive underwater labor and represents a promising restoration tool due to cost-effectiveness and scalability. This video article illustrates a protocol and tools for culturing giant kelp, Macrocystis pyrifera. It also provides a resource for further studies to address the successes and limitations of this method in field settings. We outline field and laboratory-based methods for collecting reproductive tissue, sporulating, inoculating, rearing, maintaining, and monitoring substrates seeded with early life stages using the 'green gravel' technique. The protocol simplifies and centralizes current restoration practices in this field to support researchers, managers, and stakeholders in meeting kelp conservation objectives.

Understanding the Cellular Sources of the Fractional Exhaled Nitric Oxide (FeNO) and Its Role as a Biomarker of Type 2 Inflammation in Asthma.

Fractional exhaled nitric oxide (FeNO) has gained great clinical importance as a biomarker of type 2 inflammation in chronic airway diseases such as asthma. FeNO originates primarily in the bronchial epithelium and is produced in large quantities by the enzyme inducible nitric oxide synthase (iNOS). It should be noted that nitric oxide (NO) produced at femtomolar to picomolar levels is fundamental for respiratory physiology. This basal production is induced in the bronchial epithelium by interferon gamma (IFNγ) via Janus kinases (JAK)/STAT-1 signaling. However, when there is an increase in the expression of type 2 inflammatory cytokines such as IL-4 and IL-13, the STAT-6 pathway is activated, leading to overexpression of iNOS and consequently to an overproduction of airway NO. Increased NO levels contributes to bronchial hyperreactivity and mucus hypersecretion, increases vascular permeability, reduces ciliary heartbeat, and promotes free radical production, airway inflammation, and tissue damage. In asthmatic patients, FeNO levels usually rise above 25 parts per billion (ppb) and its follow-up helps to define asthma phenotype and to monitor the effectiveness of corticosteroid treatment and adherence to treatment. FeNO is also very useful to identify those severe asthma patients that might benefit of personalized therapies with monoclonal antibodies. In this review, we revised the cellular and molecular mechanisms of NO production in the airway and its relevance as a biomarker of type 2 inflammation in asthma.

Evaluation capacity building in response to the agricultural research impact agenda: Emerging insights from Ireland, Catalonia (Spain), New Zealand, and Uruguay.

Performance-based funding and calls for public-funded science to demonstrate societal impact are encouraging public research organisations to evaluate impact, the so-called impact agenda. This paper explores evaluation methods of four fully or partially public-funded agricultural research organisations and how they are building evaluative capacity to respond to the impact agenda. Drawing on cross-organisational comparison of the readiness of each organisation to implement evaluation, the implications for improving evaluative capacity building (ECB) are discussed. This study extends the current literature on ECB, as very little has focussed on research organisations in general, and particularly agricultural research. Driven by the impact agenda, the organisations are beginning to emphasise summative evaluation. Organisational leaders valuing the demonstration of impact and commitment to building evaluation capacity are important precursors to other aspects of organisational readiness to implement evaluation. However, organisational emphasis remains on using evaluation for accountability and to improve efficiency and allocation of funding. The organisations have yet to systematically embed evaluation processes and capabilities for learning at programme and organisation-levels. There is, therefore, an opportunity to develop organisation and programme-level evaluation processes that inform each other and the pathways to impact from science. To realise this opportunity, organisations could strengthen internal and external networks of evaluation practitioners and academics to bridge the gap between the theory and practice of monitoring and evaluation for learning (MEL) and to begin to reshape organisational culture by using evaluation methods that are grounded in co-production and integrated scientific and societal values.

Clinical and Pharmacological Parameters Determine Relapse During Clopidogrel Treatment of Acute Coronary Syndrome.

The therapeutic efficacy of clopidogrel as an antiplatelet drug varies among individuals, being the mainstream hypothesis that its bioavailability depends on the individual genetic background and/or interactions with other drugs. A total of 477 patients receiving double antiaggregation therapy with aspirin and clopidogrel, after suffering a first event, were followed for 1 year to record relapse, as a surrogate end point to measure their therapeutic response, as defined by presenting with an acute coronary event (unstable angina, ST-segment-elevation myocardial infarction, or non-ST-segment-elevation myocardial infarction), stent thrombosis/restenosis, or cardiac mortality. Anthropometric, clinical, and pharmacological variables along with CYP2C19 genotypes were analyzed for their association with the disease relapse phenotype. Only 75 patients (15%) suffered a relapse, which occurred during the first 6 months of therapy, with a peak at 4.5 months. An initial univariate analysis identified that patients in the relapse group were significantly older (67.4 ± 11.0 vs 61.6 ± 12.3 years old) and presented with diffuse coronary disease, insulin-dependent type 2 diabetes mellitus dyslipidemia, and arterial hypertension. A poor clinical response to the platelet antiaggregation regime also occurred more frequently among patients taking acenocoumarol and calcium channel blockers, along with aspirin and clopidogrel, while no association was found according to CYP2C19 genotypes. A retrospective multivariate analysis indicated that patients belonging to the nonresponder phenotype to treatment with aspirin and clopidogrel were older, presented with diffuse coronary disease, a group largely overlapping with type 2 insulin-dependent diabetes mellitus, and were taking dihidropyrimidinic calcium channel blockers.

Evaluation of a new synthetic plug in the treatment of anal fistulas: results of a pilot study.

BACKGROUND: The treatment of anal fistulas using plugs is a very promising method because of its simplicity and ability to be carried out on an ambulatory basis. If unsuccessful, it does not compromise subsequent alternative surgical techniques and/or products. However, success rates are variable. OBJECTIVE: This pilot study was designed to investigate the safety and effectiveness of a new synthetic plug in the treatment of transsphincteric anal fistulas. DESIGN: This was a prospective observational study. SETTING: Patients were treated at 2 colorectal surgery centers in Spain (Seville and Huelva). INTERVENTIONS: Anal fistulas were treated with a fistula plug made of bioabsorbable polymers (67% polyglycolide, 33% trimethylene carbonate). PATIENTS: Starting in January 2009, consecutive adult patients with transsphincteric anal fistulas were evaluated. MAIN OUTCOME MEASURES: Outcome measures included rates of successful fistula closure, complications, and continence (Jorge-Wexner incontinence score), assessed postoperatively at 1 week and again at 1, 3, 6, and 12 months. Healing was determined by clinical examination by a surgeon blinded for the intervention. RESULTS: A total of 19 patients (18 men, 1 woman) with transsphincteric anal fistulas were included in the study. The median age was 49 (range, 33-65) years. Of these patients, 12 presented with fistula relapse. The median time from onset of symptoms to surgery was 12 (range, 6-120) months. Three patients had previously placed setons. The follow-up duration was 12 months. Relapse occurred in 16 patients (with a perianal abscess in 1), and successful closure was observed in 3 patients (15.8%). LIMITATIONS: The number of patients was small, and time was needed for the learning curve of the technique. CONCLUSIONS: This study indicates that the new synthetic plug is safe, but the fistula closure rate was low. Randomized studies are needed to further determine the role of the bioabsorbable synthetic plug in the management of anal fistulas.

Disentangling the Drivers of Obesity: An Analytical Framework Based on Socioeconomic and Intrapersonal Factors.

Obesity is increasing at exponential rates in developed economies despite the numerous policy interventions being implemented. The causes of obesity are multifactorial demanding a holistic review for targeted intervention. This study, therefore, provides a holistic overview of multiple factors affecting body weights i.e., socioeconomic and intrapersonal factors. We used data from a household and experimental survey carried out in Spain (Barcelona) in 2014. A non-linear path analysis was used considering the non-linear relationships that might exist between these factors and body weight. Results confirm non-linear relationships between some socioeconomic, intrapersonal factors and body weight. Among the intrapersonal factors, obesity is directly influenced by volitional control of obesity, attitude toward obese persons, holding a correct body image and body image dissatisfaction. Socioeconomic factors that have significant influence on obesity were age, education and gender. Risk attitudes do not correlate with obesity.

The metabesity factor HMG20A potentiates astrocyte survival and reactive astrogliosis preserving neuronal integrity.

Rationale: We recently demonstrated that the 'Metabesity' factor HMG20A regulates islet beta-cell functional maturity and adaptation to physiological stress such as pregnancy and pre-diabetes. HMG20A also dictates central nervous system (CNS) development via inhibition of the LSD1-CoREST complex but its expression pattern and function in adult brain remains unknown. Herein we sought to determine whether HMG20A is expressed in the adult CNS, specifically in hypothalamic astrocytes that are key in glucose homeostasis and whether similar to islets, HMG20A potentiates astrocyte function in response to environmental cues. Methods: HMG20A expression profile was assessed by quantitative PCR (QT-PCR), Western blotting and/or immunofluorescence in: 1) the hypothalamus of mice exposed or not to either a high-fat diet or a high-fat high-sucrose regimen, 2) human blood leukocytes and adipose tissue obtained from healthy or diabetic individuals and 3) primary mouse hypothalamic astrocytes exposed to either high glucose or palmitate. RNA-seq and cell metabolic parameters were performed on astrocytes treated or not with a siHMG20A. Astrocyte-mediated neuronal survival was evaluated using conditioned media from siHMG20A-treated astrocytes. The impact of ORY1001, an inhibitor of the LSD1-CoREST complex, on HMG20A expression, reactive astrogliosis and glucose metabolism was evaluated in vitro and in vivo in high-fat high-sucrose fed mice. Results: We show that Hmg20a is predominantly expressed in hypothalamic astrocytes, the main nutrient-sensing cell type of the brain. HMG20A expression was upregulated in diet-induced obesity and glucose intolerant mice, correlating with increased transcript levels of Gfap and Il1b indicative of inflammation and reactive astrogliosis. Hmg20a transcript levels were also increased in adipose tissue of obese non-diabetic individuals as compared to obese diabetic patients. HMG20A silencing in astrocytes resulted in repression of inflammatory, cholesterol biogenesis and epithelial-to-mesenchymal transition pathways which are hallmarks of reactive astrogliosis. Accordingly, HMG20A depleted astrocytes exhibited reduced mitochondrial bioenergetics and increased susceptibility to apoptosis. Neuron viability was also hindered in HMG20A-depleted astrocyte-derived conditioned media. ORY1001 treatment rescued expression of reactive astrogliosis-linked genes in HMG20A ablated astrocytes while enhancing cell surface area, GFAP intensity and STAT3 expression in healthy astrocytes, mimicking the effect of HMG20A. Furthermore, ORY1001 treatment protected against obesity-associated glucose intolerance in mice correlating with a regression of hypothalamic HMG20A expression, indicative of reactive astrogliosis attenuation with improved health status. Conclusion: HMG20A coordinates the astrocyte polarization state. Under physiological pressure such as obesity and insulin resistance that induces low grade inflammation, HMG20A expression is increased to induce reactive astrogliosis in an attempt to preserve the neuronal network and re-establish glucose homeostasis. Nonetheless, a chronic metabesity state or functional mutations will result in lower levels of HMG20A, failure to promote reactive astrogliosis and increase susceptibility of neurons to stress-induced apoptosis. Such effects could be reversed by ORY1001 treatment both in vitro and in vivo, paving the way for a new therapeutic approach for Type 2 Diabetes Mellitus.

Linking risk attitudes, time preferences, and body mass index in Catalonia.

Obesity is projected to increase in the coming years, despite the various socioeconomic policies implemented by governments and policy makers. As a result, some studies have suggested that obesity should be looked at from a psychological point of view, that is, individuals' propensity to become addicted to the consumption of fat-rich foods. Although previous studies have supported this, the results have been inconclusive: methodologically and geographically. This study uses a robust approach to elicit the risk and time preferences of food consumers. It goes further to ascertain the correlations between these parameters and obesity. Despite the methodological and geographical differences, our results support a strong relationship between body mass Index and risk aversion, but not for loss aversion. In addition, time discounting significantly influences individuals' propensity to increase body mass Index.

Dissecting the Brain/Islet Axis in Metabesity.

The high prevalence of type 2 diabetes mellitus (T2DM), together with the fact that current treatments are only palliative and do not avoid major secondary complications, reveals the need for novel approaches to treat the cause of this disease. Efforts are currently underway to identify therapeutic targets implicated in either the regeneration or re-differentiation of a functional pancreatic islet ß-cell mass to restore insulin levels and normoglycemia. However, T2DM is not only caused by failures in ß-cells but also by dysfunctions in the central nervous system (CNS), especially in the hypothalamus and brainstem. Herein, we review the physiological contribution of hypothalamic neuronal and glial populations, particularly astrocytes, in the control of the systemic response that regulates blood glucose levels. The glucosensing capacity of hypothalamic astrocytes, together with their regulation by metabolic hormones, highlights the relevance of these cells in the control of glucose homeostasis. Moreover, the critical role of astrocytes in the response to inflammation, a process associated with obesity and T2DM, further emphasizes the importance of these cells as novel targets to stimulate the CNS in response to metabesity (over-nutrition-derived metabolic dysfunctions). We suggest that novel T2DM therapies should aim at stimulating the CNS astrocytic response, as well as recovering the functional pancreatic ß-cell mass. Whether or not a common factor expressed in both cell types can be feasibly targeted is also discussed.

CYP2C19 or CYP3A5 Genotyping Does Not Predict Clinical Response to Clopidogrel.

Along with aspirin, clopidogrel has been a widely used antiplatelet therapeutic regimen. Although generally well tolerated, its efficacy varies among individuals, with the main hypothesis that its bioavailability relies on its bioconversion to the active compound, which, in turn, depends on the genetic background and/or interactions with other drugs. To determine which factors influenced response in our patients, 368 patients receiving combined antiaggregation therapy with aspirin and clopidogrel were followed for 1 year to record 30 novel cardiovascular acute events. This clinical relapse was considered a surrogate end point to measure therapeutic response under the influence of the CYP2C19*2, *3, and *17 and CYP3A5*3 alleles, as well as the effects of concomitant medication and the presence of known cardiovascular risk factors and comorbidity. We show that either single CYP2C19 or CYP3A5 genotyping or combined were not useful to predict clinical efficacy in this cohort. Rather than genetic testing, we have found that clinical observations such as suffering type 2 diabetes mellitus requiring insulin, having several vessels affected, and concurrent medication with calcium channel blockers, regardless of CYP3A5 genotype or drug class were, in that order, the strongest independent predictors of disease relapse.

[Neumatosis quística intestinal: reporte de un caso]. / Pneumatosis cystoides intestinalis: a case report.

ANTECEDENTES: La neumatosis quística intestinal es una condición infrecuente, caracterizada por la formación de quistes de contenido gaseoso debajo de la mucosa y la serosa intestinales. CASO CLÍNICO: Mujer de 84 años, con antecedente de artritis reumatoide en tratamiento inmunosupresor, intervenida hace 2 años por neumoperitoneo, con diagnóstico de diverticulosis yeyunal y enfisema mesentérico, acude con cuadro de dolor abdominal difuso de 2 días de evolución, sin otra sintomatología. En la radiografía de abdomen se observa neumoperitoneo con elevación del hemidiafragma derecho y distensión de asas del intestino delgado. Ante la sospecha de perforación de víscera hueca se decide intervención quirúrgica, en la cual se diagnostica a la paciente de neumatosis quística intestinal. CONCLUSIÓN: La neumatosis quística intestinal es de causa desconocida, aunque en un elevado porcentaje de pacientes se ha visto asociada a enfermedades pulmonares obstructivas, enfermedades del tejido conectivo, inmunosupresión o enfermedades gastrointestinales. Se localiza más frecuentemente en el colon y el intestino delgado. Se diagnostica principalmente mediante pruebas de imagen (radiografía o tomografía computarizada). El tratamiento es conservador, realizándose intervención quirúrgica si existe sospecha de necrosis intestinal. Es difícil el diagnóstico diferencial con un neumoperitoneo por perforación de víscera hueca. BACKGROUND: Pneumatosis cystoides intestinalis is an infrequent condition, characterized by the formation of gaseous content cysts under the mucosa and intestinal serous. CLINICAL CASE: 84-year-old woman, with a history of rheumatoid arthritis under immunosuppressive treatment, operated 2 years ago by pneumoperitoneum, where she was diagnosed of jejunal diverticulosis and mesenteric emphysema, with diffuse abdominal pain of 2 days of evolution, without other symptoms. In abdominal radiography: pneumoperitoneum with elevation of right hemidiaphragm and distention of small intestine. Given the suspicion of perforation of the intestinal wall, surgical intervention was decided, in which the patient was diagnosed with pneumatosis cystoides intestinalis. CONCLUSION: Pneumatosis cystoides intestinalis has an unknown etiology, although in a high percentage of patients it has been associated with obstructive pulmonary pathologies, connective tissue diseases, immunosuppression or gastrointestinal diseases. It is located more frequently in the colon and small intestine. It is diagnosed mainly through imaging tests (radiography or computed tomography). The treatment is conservative, performing surgical intervention if there is suspicion of intestinal necrosis; being difficult the differential diagnosis with a pneumoperitoneum by perforation of hollow viscera..

The type 2 diabetes-associated HMG20A gene is mandatory for islet beta cell functional maturity.

HMG20A (also known as iBRAF) is a chromatin factor involved in neuronal differentiation and maturation. Recently small nucleotide polymorphisms (SNPs) in the HMG20A gene have been linked to type 2 diabetes mellitus (T2DM) yet neither expression nor function of this T2DM candidate gene in islets is known. Herein we demonstrate that HMG20A is expressed in both human and mouse islets and that levels are decreased in islets of T2DM donors as compared to islets from non-diabetic donors. In vitro studies in mouse and human islets demonstrated that glucose transiently increased HMG20A transcript levels, a result also observed in islets of gestating mice. In contrast, HMG20A expression was not altered in islets from diet-induced obese and pre-diabetic mice. The T2DM-associated rs7119 SNP, located in the 3' UTR of the HMG20A transcript reduced the luciferase activity of a reporter construct in the human beta 1.1E7 cell line. Depletion of Hmg20a in the rat INS-1E cell line resulted in decreased expression levels of its neuronal target gene NeuroD whereas Rest and Pax4 were increased. Chromatin immunoprecipitation confirmed the interaction of HMG20A with the Pax4 gene promoter. Expression levels of Mafa, Glucokinase, and Insulin were also inhibited. Furthermore, glucose-induced insulin secretion was blunted in HMG20A-depleted islets. In summary, our data demonstrate that HMG20A expression in islet is essential for metabolism-insulin secretion coupling via the coordinated regulation of key islet-enriched genes such as NeuroD and Mafa and that depletion induces expression of genes such as Pax4 and Rest implicated in beta cell de-differentiation. More importantly we assign to the T2DM-linked rs7119 SNP the functional consequence of reducing HMG20A expression likely translating to impaired beta cell mature function.