[Diabetes control and visits to the family doctor during the COVID-19 pandemic: a multicenter study in primary care]. / Control de diabetes y consultas al médico de familia durante la pandemia de COVID-19: estudio multicéntrico en atención primaria.

OBJECTIVES: To determine whether in patients with type 2 diabetes (DM2) the changes in their relationship with family doctors during the COVID-19 pandemic, in-person (iPC) and telematic (TC) consultations, were associated with control of their disease. DESIGN: Multicentric study of retrospective follow-up. SETTING: Seven health centers in Tenerife, Spain. PARTICIPANTS: 3543 patients with DM2. MAIN MEASUREMENTS: Sex, age, iPC, TC and DM2 control using glycosylated hemoglobin (A1c) during the period 2019-2021. Logistic regression models were fitted with DM2 control as an effect, and with the other measurements as independent variables. RESULTS: 50% were women. 38% were less than 65 years old. A1c was measured in 84% of patients in 2019, 68% in 2020, and 77% in 2021. 58.4% had good control in 2019, 46.1% in 2020, and 50.3% in 2021. Median iPC were 7 in 2019, 4 in 2020 and 5 in 2021 (p<0.001). The OR(95%CI) of good control in 2019 were 1.04(1.04-1.05) per year of age and 1.03(1.01-1.04) for each iPC; In 2020 they were 1.04 (1.03-1.05) per year of age, 1.05 (1.04-1.07) for each iPC and 1.04 (1.02-1.07) for each TC; in 2021 they were 1.04 (1.04-1.05) per year of age, 1.05 (1.03-1.06) for each iPC and 1.02 (1.00-1.04) for each TC. CONCLUSIONS: The control of patients with DM2 during the period 2019-2021 had a direct relationship with the change in the frequency of consultations at the health center, with differences depending on the type of consultation and the age of the patient.

Insights from the clinical phenotype of subjects with Laron syndrome in Ecuador.

The Ecuadorian cohort of subjects with LS has taught us valuable lessons since the late 80's. We have learned about migration of Sephardic Jews to our country, their isolation in remote hamlets and further inbreeding. These geographical, historical and social determinants induced dissemination of a growth hormone (GH) receptor mutation which widely occurred in those almost inaccessible villages. Consequently, the world's largest Laron syndrome (LS) cohort emerged in Loja and El Oro, two of the southern provinces of Ecuador. We have been fortunate to study these patients since 1987. New clinical features derived from GH insensitivity, their growth patterns as well as treatment with exogenous insulin-like growth factor I (IGF-I) have been reported. Novel biochemical characteristics in the field of GH insensitivity, IGFs, IGF binding proteins (BP) and their clinical correlates have also been described. In the last few years, studies on the morbidity and mortality of Ecuadorian LS adults surprisingly demonstrated that despite obesity, they had lower incidence of diabetes and cancer than their relatives. These events were linked to their metabolic phenotype of elevated but ineffective GH concentrations and low circulating IGF-I and IGFBP-3. It was also noted that absent GH counter-regulation induces a decrease in insulin resistance (IR), which results in low but highly efficient insulin levels which properly handle metabolic substrates. We propose that the combination of low IGF-I signaling, decreased IR, and efficient serum insulin concentrations are reasonable explanations for the diminished incidence of diabetes and cancer in these subjects.

[Evolution of Smoking According to Social Class in the Adult Population of the Canary Islands During 2000-2015: Follow-up of the CDC-Canary Cohort]. / Evolución del tabaquismo según clase social en la población adulta de las Islas Canarias durante el periodo 2000-2015: seguimiento de la cohorte CDC-Canarias.

OBJECTIVE: To determine the status of tobacco consumption in the Canary Islands during 2000-2015, according to social class. LOCATION: Canary Islands. PARTICIPANTS: General population cohort, with contacts in 2000 (n=6,729), 2008 (n=6,171) and 2015 (n=4,705). MAIN MEASUREMENTS: Smoking, gender, age, and social class. RESULTS: Consumption decreased by 6% (5-7%, P<.001) in general, being more accentuated in the period 2000-2008 (5%). The decrease was greater in men, although they continued to smoke more than women, with a prevalence of 25% (24-26%) compared to 18% (17-19%, P<.001). A decrease in consumption was only observed in the younger groups (6% [3-5%], P=.011) and intermediate ages (7% [6-8%], P<.001). A similar decrease was observed in all the social classes, but there was a higher prevalence of smoking in the upper class: 24% (23-25%) in 2015 (P<.001). By jointly assessing gender, age, and social class, younger and middle age men had the greatest decreases in consumption: 8% (7-9%) low and upper classes, 10% (9-11%) middle class. In the lower social class, younger women continue to smoke more (27%) although more of them quit smoking (14%), a phenomenon that occurred in the middle class at intermediate ages. CONCLUSIONS: The evolution of tobacco consumption in the Canary Islands follows a pattern similar to that of mainland Spain. The abandonment of tobacco consumption has slowed down in the period 2008-2015, especially in men, and middle and upper social classes.

Effect of conscious sedation with midazolam and fentanyl on the overall quality of colonoscopy: a prospective and randomized study.

INTRODUCTION: a prospective, randomized study was performed to assess the influence of conscious sedation on the overall quality of colonoscopy, simultaneously quantifying its effect on the scientific quality, perceived quality and patient safety. METHODS: patients referred for a colonoscopy were included in the study and were randomized to receive or not receive sedation. Demographic data, indication for colonoscopy, cecal intubation, introduction and withdrawal time, resected adenomas and complications during the exploration were collected. Thirty days later, a satisfaction questionnaire was performed (GHAA 9-me) and patients were asked about complications after the examination. RESULTS: a total of 5,328 patients were included, the average age was 62 ± 15.22 years, 47% were male, 3,734 were sedated and 1,594 were not sedated. The sedated patients had a shorter endoscope insertion time (7'20 ± 2'15 min vs 6'15 ± 3'12 min, p < 0.019), a higher rate of cecal intubations (96% vs 88%, p < 0.05), longer withdrawal time (7'20 ± 2'15 min vs 6'15 ± 3'12 min, p < 0.01) and higher adenoma detection rates (22% vs 17%, p < 0.05). The use of sedation reduced discomfort during and after the exploration, without increasing the complications. The satisfaction questionnaire score was higher (23.6 ± 1.5 vs 16.6 ± 4.8, p < 0.001) in the sedated patients. CONCLUSIONS: superficial sedation not only reduces patient discomfort but also improves the overall quality of the colonoscopy. Therefore, we must consider the use of sedation as an essential part of colonoscopy.

Prevalence and characteristics of methicillin-resistant staphylococci in goats on the island of Tenerife, Spain.

The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus (MRS) in healthy goats on the Island of Tenerife, Spain, as well as to identify the phenotypic and genotypic characteristics of the strains found. A cross-sectional prevalence study was conducted. A total of 158 goats from 15 different farms were sampled between September 2017 and January 2018. The percentage of positive samples of methicillin-resistant Staphylococcus aureus (MRSA) was 15.8% (25/158) and that of methicillin-resistant coagulase-negative staphylococci (MRCoNS) was 6.9% (11/158). All MRSA isolates from goats belonged to one clonal group showing Multi-Locus Sequence type 398. All strains studied (n = 36) were resistant to non-carbapenem beta-lactam antibiotics and susceptible to teicoplanin, linezolid, vancomycin, rifampicin, quinupristin-dalfospristin and mupirocine. In MRSA isolates, the highest percentage of resistance obtained, besides beta-lactam non-carbapenem antibiotics, was to trimethoprim-sulphamethoxazole and, in the case of MRCoNS isolates, to phosphomycin and erythromycin. A total of 12 resistance patterns were obtained, presenting differences between patterns obtained for MRSA and MRCoNS, with 7 different patterns for MRSA and 5 for MRCoNS. We therefore consider it essential to expand the epidemiological study of these strains of animal origin, as well as to increase surveillance and control measures at all stages of the food chain.

Brain Structure and Function Associated with Younger Adults in Growth Hormone Receptor-Deficient Humans.

Growth hormone receptor deficiency (GHRD) results in short stature, enhanced insulin sensitivity, and low circulating levels of insulin and insulin-like growth factor 1 (IGF-1). Previous studies in mice and humans suggested that GHRD has protective effects against age-related diseases, including cancer and diabetes. Whereas GHRD mice show improved age-dependent cognitive performance, the effect of GHRD on human cognition remains unknown. Using MRI, we compared brain structure, function, and connectivity between 13 people with GHRD and 12 unaffected relatives. We assessed differences in white matter microstructural integrity, hippocampal volume, subregional volumes, and cortical thickness and surface area of selected regions. We also evaluated brain activity at rest and during a hippocampal-dependent pattern separation task. The GHRD group had larger surface areas in several frontal and cingulate regions and showed trends toward larger dentate gyrus and CA1 regions of the hippocampus. They had lower mean diffusivity in the genu of the corpus callosum and the anterior thalamic tracts. The GHRD group showed enhanced cognitive performance and greater task-related activation in frontal, parietal, and hippocampal regions compared with controls. Furthermore, they had greater functional synchronicity of activity between the precuneus and the rest of the default mode network at rest. The results suggest that, compared with controls, GHRD subjects have brain structure and function that are more consistent with those observed in younger adults reported in previous studies. Further investigation may lead to improved understanding of underlying mechanisms and could contribute to the identification of treatments for age-related cognitive deficits.SIGNIFICANCE STATEMENT People and mice with growth hormone receptor deficiency (GHRD or Laron syndrome) are protected against age-related diseases including cancer and diabetes. However, in humans, it is unknown whether cognitive function and brain structure are affected by GHRD. Using MRI, we examined cognition in an Ecuadorian population with GHRD and their unaffected relatives. The GHRD group showed better memory performance than their relatives. The differences in brain structure and function that we saw between the two groups were not consistent with variations typically associated with brain deficits. This study contributes to our understanding of the connection between growth genes and brain aging in humans and provides data indicating that GHR inhibition has the potential to protect against age-dependent cognitive decline.

Austerity Policies and Mortality in Spain After the Financial Crisis of 2008.

OBJECTIVES: To analyze mortality in Spain and the United States before and after these countries implemented divergent policies in response to the financial crisis of 2008. METHODS: We examined mortality statistics in both countries in the years 2000 to 2015. Spain started austerity policies in 2010. We compared differences in mortality ratios, on the basis of trends and effect size analysis. RESULTS: During 2000 to 2010, overall mortality rates (r = 0.98; P < .001; Cohen's d = -0.228) decreased in both countries. In 2011, this trend changed abruptly in Spain, where observed mortality surpassed expected mortality by 29% in 2011 and by 41% in 2015. By contrast, observed mortality surpassed expected mortality in the United States by only 8% in 2015. As the mortality statistics diverged, the effect size greatly increased (d = 7.531). During this 5-year period, there were 505 559 more deaths in Spain than the expected number, while in the United States the difference was 431 501 more deaths despite the 7-fold larger population in the United States compared with Spain. CONCLUSIONS: The marked excess mortality in 2011 to 2015 in Spain is attributable to austerity policies.

[Application of the Smoking Scale for Primary Care (ETAP) in clinical practice]. / Aplicación de la Escala de Tabaquismo para Atención Primaria (ETAP) en la práctica clínica.

OBJECTIVE: To determine if the ETAP smoking scale, which measures accumulated exposure to tobacco, both actively and passively, is applicable and effective in the clinical practice of Primary Care for the prevention of acute myocardial infarction (AMI). Location Barranco Grande Health Centre in Tenerife, Spain. DESIGN: A study of 61 cases (AMI) and 144 controls. Sampling with random start, without matching. COR-II curves were analysed, and effectiveness was estimated using sensitivity and negative predictive value (NPV). A questionnaire was provided to participating family physicians on the applicability of ETAP in the clinic. RESULTS: The opinion of the participating physicians was unanimously favourable. ETAP was easy to use in the clinic, required less than 3min per patient, and was useful to reinforce the preventive intervention. The ETAP COR-II curve showed that 20years of exposure was the best cut-off point, with an area under the curve of 0.70 (95%CI: 0.62-0.78), and a combination of sensitivity (98%) and NPV (96%) for AMI. When stratifying age and gender, all groups achieved sensitivities and NPVs close to 100%, except for men aged ≥55years, in whom the NPV fell to 75%. CONCLUSIONS: The results indicate that ETAP is a valid tool that can be applied and be effective in the clinical practice of Primary Care for the prevention of AMI related to smoking exposure.

Telomere shortening and accelerated aging in COPD: findings from the BODE cohort.

BACKGROUND: Chronic Obstructive Pulmonary Disease (COPD) may be associated with accelerated aging. Telomere shortening is a biomarker of aging. Cross-sectional studies describe shorter telomeres in COPD compared with matched controls. No studies have described telomere length trajectory and its relationship with COPD progression. We investigated telomere shortening over time and its relationship to clinical and lung function parameters in a COPD cohort and smoker controls without COPD. METHODS: At baseline leukocyte telomere length was measured by qPCR in 121 smokers with COPD and 121 without COPD matched by age (T/S0). The measurements were repeated in 70 of those patients with COPD and 73 non-COPD smokers after 3 years of follow up (T/S3). RESULTS: At initial measurement, telomeres were shorter in COPD patients when compared to smoker controls (T/S = 0.68 ± 0.25 vs. 0.88 ± 0.52, p = 0.003) independent from age and sex. During the follow-up period, we observed an accelerated telomere shortening in individuals with COPD in contrast to smoker controls (T/S0 = 0.66 ± 0.21 vs. T/S3 = 0.46 ± 0.16, p < 0.001, for the patients with COPD and T/S0 = 0.83 ± 0.56 vs. T/S3 = 0.74 ± 0.52, p = 0.023 for controls; GLIM, p = 0.001). This shortening was inversely related to the baseline telomere length (r = -0.49, p < 0.001). No significant relationship was found between the rate of change in telomere length and change in lung function in the patients with COPD (p > 0.05). CONCLUSIONS: Compared with smokers, patients with COPD have accelerated telomere shortening and this rate of attrition depends on baseline telomere length. Furthermore, the telomere length and its rate of shortening did not relate to clinical and lung function parameters changes over 3 years of follow-up.

A hospital-based matched case-control study to identify risk factors for clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers.

Asymptomatic colonisation of the gastrointestinal tract by carbapenemase-producing Enterobacteriaceae is an important reservoir for transmission, which may precede infection. This retrospective observational case-control study was designed to identify risk factors for developing clinical infection with OXA-48-producing Klebsiella pneumoniae in rectal carriers during hospitalisation. Case patients (n = 76) had carbapenemase-producing K. pneumoniae (CPKP) infection and positive rectal culture for CPKP. Control patients (n = 174) were those with rectal colonisation with CPKP but without CPKP infection. Multivariate analysis identified the presence of a central venous catheter (OR 4·38; 95% CI 2·27-8·42; P = 0·008), the number of transfers between hospital units (OR 1·27; 95% CI (1·06-1·52); P < 0·001) and time at risk (OR 1·02 95% CI 1·01-1·03; P = 0·01) as independent risk factors for CPKP infection in rectal carriers. Awareness of these risk factors may help to identify patients at higher risk of developing CPKP infection.

[Validation of the Nursing Assessment System of the Pediatric Primary Care Emergency: VEUPAP]. / Validación del sistema de valoración enfermera de la urgencia pediátrica en Atención Primaria VEUPAP.

Objective: Measure the validity, reliability and consistency of two alternative diagnostic systems, Nurse Pediatric Emergency Assessment for Primary Care system (VEUPAP) and web_e-PAT®, using expert pediatricians judgment as a gold standard. Material and Methods: Random sample of 300 children aged 0-14 years treated at the Pediatric Urgency Service Dr. Jaime Chaves in Santa Cruz de Tenerife between March 2009 and March 2010. Demographics data, time, presentation of complications and referrals to high, triage results according VEUPAP and web_e-PAT®, medical discharge and interview results to escort the child report, were registered. Sensitivity, specificity, frequency of false positive and negative predictive values of results, their concordance with the gold standard, and reliability of both methods, were estimated. Results: VEUPAP offers better values that web_e-PAT® with sensitivity 94% (95% Cl: 91-97%) vs. 36% (95% Cl: 31-41%), specificity 93(90-96)% vs. 87(83-91)%, positive predictive value of 89 (86-92)% vs. 63(58-68)%, and negative 96(94-98)% vs. 69(64-74)%, yield a4 vs. 3 times more, according to expert pediatrician 84(80-88)5 vs. 12(9-15)% reliability and 64(59-69)% vs. 59(54-63)% according to the weighted kappa Cohen (p < 0.001). Three levels lower and upper of triage discrepancies do not occur with any of the systems, the discrepancy in lower and upper triage at 2 levels do not occur with VEUPAP and is 14% and 4% respectively with web_e-PAT® (p = 0.032-0.045). Most of the discrepancies occur with triage level 1 being for VEUPAP 2-8% and 10-36% for web_e-PAT® (p < 0.001). The time consumption for both systems reached significance only for priority level 3: 4 (2-7) vs. 4 minutes (2-14), respectively (p = 0.044). Conclusions: VEUPAP is a homogeneous and systematic objective tool. The characteristics of accuracy, validity, accuracy, reliability, usefulness and ease of use make it suitable to assessment and classification pediatric patients in primary care emergency.

[ETAP: A smoking scale for Primary Health Care]. / ETAP: una escala de tabaquismo para la atención primaria de salud.

OBJECTIVE: To obtain a scale of tobacco exposure to address smoking cessation. DESIGN: Follow-up of a cohort. Scale validation. SETTING: Primary Care Research Unit. Tenerife. PARTICIPANTS: A total of 6729 participants from the "CDC de Canarias" cohort. METHODS: A scale was constructed under the assumption that the time of exposure to tobacco is the key factor to express accumulated risk. Discriminant validity was tested on prevalent cases of acute myocardial infarction (AMI; n=171), and its best cut-off for preventive screening was obtained. Its predictive validity was tested with incident cases of AMI (n=46), comparing the predictive power with markers (age, sex) and classic risk factors of AMI (hypertension, diabetes, dyslipidaemia), including the pack-years index (PYI). RESULTS: The scale obtained was the sum of three times the years that they had smoked plus years exposed to smoking at home and at work. The frequency of AMI increased with the values of the scale, with the value 20 years of exposure being the most appropriate cut-off for preventive action, as it provided adequate predictive values for incident AMI. The scale surpassed PYI in predicting AMI, and competed with the known markers and risk factors. CONCLUSION: The proposed scale allows a valid measurement of exposure to smoking and provides a useful and simple approach that can help promote a willingness to change, as well as prevention. It still needs to demonstrate its validity, taking as reference other problems associated with smoking.

Obesity, diabetes and cancer: insight into the relationship from a cohort with growth hormone receptor deficiency.

Obesity with insulin-resistant diabetes and increased cancer risk is a global problem. We consider the alterations of metabolism attendant on the underlying pathogenic overnutrition and the role of the growth hormone (GH)-IGF-1 axis in this interaction. Obesity-induced insulin resistance is a determinant of diabetes. Excess glucose, and an elevated concentration of insulin acting through its own receptors along with complex interactions with the IGF-1 system, will add extra fuel and fuel signalling for malignant growth and induce anti-apoptotic activities, permitting proliferation of forbidden clones. In Ecuador there are ~100 living adults with lifelong IGF-1 deficiency caused by a GH receptor (GHR) mutation who, despite a high percentage of body fat, have markedly increased insulin sensitivity compared with age- and BMI-matched control relatives, and no instances of diabetes, which is present in 6% of unaffected relatives. Only 1 of 20 deceased individuals with GHR deficiency died of cancer vs 20% of ~1,500 relatives. Fewer DNA breaks and increased apoptosis occurred in cell cultures exposed to oxidant agents following addition of serum from GHR-deficient individuals vs serum from control relatives. These changes were reversible by adding IGF-1 to the serum from the GHR-deficient individuals. The reduction in central regulators of pro-ageing signalling thus appears to be the result of an absence of GHR function. The complex inter-relationship of obesity, diabetes and cancer risk is related to excess insulin and fuel supply, in the presence of heightened anti-apoptosis and uninhibited DNA damage when GHR function is normal.

Does the new staging system proposed for mycosis fungoides and Sézary syndrome provide reliable agreement for T1 and T2 disease?

BACKGROUND: Patch or plaque stages in mycosis fungoides (MF) have different prognoses. The recent staging system proposed for MF discriminates between patches and plaques based upon clinical features. OBJECTIVE: To estimate interdermatologist agreement on the morphological evaluation of MF lesions. METHODS: Twenty-four patients with MF were enrolled. Two dermatologists evaluated every lesion face to face and independently with respect to the patch-plaque status. Cohen's κ was used to determine the rate of agreement. RESULTS: Agreement was 67% with respect to the patch or plaque status [95% confidence interval (CI) = 49-85%; p < 0.001]. Current systemic treatment (56%; p = 0.01) was associated with lower agreement. Younger age at diagnosis [odds ratio (OR) 1.03 (95% CI 1.02-1.05)], younger age at enrolment [OR 1.03 (95% CI 1.02-1.04)] and time on systemic treatment [OR 1.02 (95% CI 1.01-1.04)] were independent risk factors for disagreement (p < 0.001). CONCLUSION: The new system for MF staging carries a significant risk of disagreement regarding patch and plaque subsets.

IL-8 gene variants are associated with lung function decline and multidimensional BODE index in COPD patients but not with disease susceptibility: a validation study.

BACKGROUND AND OBJECTIVE: COPD is a leading cause of dead worldwide and tobacco smoking is its major risk factor. IL8 is a proinflammatory chemokine mainly involved in the acute inflammatory reaction. The aim of this study was to test the association of IL-8, CXCR1 and CXCR2 gene variants and COPD susceptibility as part of a replication study and explore the effect of these variations in disease progression. METHODS: 9 tagSNPs were genotyped in 728 Caucasian individuals (196 COPD patients, 80 smokers and 452 non-smoking controls). Pulmonary compromise was evaluated using spirometry and clinical parameters at baseline and annually over a 2 years period. We also determined plasma levels of TNF-α, IL-6, IL-8 and IL-16 in COPD patients. RESULTS: There was a lack of association between gene variants or haplotypes with predisposition to COPD. No correlation was observed between the polymorphisms and cytokines levels. Interestingly, significant associations were found between carriers of the rs4073A (OR = 3.53, CI 1.34-9.35, p = 0.01), rs2227306C (OR = 5.65, CI 1.75-18.88, p = 0.004) and rs2227307T (OR = 4.52, CI = 1.49-12.82, p = 0.007) alleles in the IL-8 gene and patients who scored higher in the BODE index and showed an important decrease in their FEV1 and FVC during the 2 years follow-up period (p < 0.05). CONCLUSIONS: Despite no association was found between the studied genes and COPD susceptibility, three polymorphisms in the IL-8 gene appear to be involved in a worse progression of the disease, with an affectation beyond the pulmonary function and importantly, a reduction in lung function along the follow-up years.

[NURSE PEDIATRIC EMERGENCY VALUATION IN PRIMARY CARE: QUALITY RECORD AND PATIENTS AND NURSES SATISFACTION WITH TOOL VEUPAP]. / Valoración enfermera de las Urgencias Pediátricas en Atención Primaria.

OBJECTIVE: To value the degree of completion of VEUPAP record, the level of satisfaction of the accompanists otcrilaren witn nursing care and nurse satisfaction. DESIGN: Descriptive study. There was valued the cumplimentation of record of global and specific form by nurse according to defined quality criteria. The satisfaction of the accompanists was valued by the AMABLE questionnaire, the nurses satisfaction with the use of VEUPAP by the CSLPS-EAP and the personal accomplishment in the work by the MBI in his validated Spanish version. RESULTS: 266 VEUPAP cases were evaluated. The general compliance of the items exceeds 95 (92-98) %, except for three items. Completion of protocols fever, respiratory distress, gastrointestinal, and abdominal pain is 95 (92-98) %, 93(90-96) %, 90 (86-94) %--and 67 (61-73) % respectively. More than 95 (93-97) % users referring to be satisfied with the nurses attention. The 100 (100-100) % of the nurses are very satisfied with their tasks and activities and personal accomplishment they get, 88(84-92) % with the quality of patient care and achievement of objectives. All feel quite satisfied with their degree of autonomy. Job instability represents 50(44-56) % of dissatisfaction. The EE is low for 94% of nurses and a medium for 6%, the DP high for 17% and low for 13% and the PA low for 53% and medium for 47%. CONCLUSIONS: Quality of registration, user satisfaction and the nurse who provides care satisfaction are three cornerstones of pediatric emeraency care. VEUPAP impacts positively on these three aspects.

Longitudinal assessment in COPD patients: multidimensional variability and outcomes.

The value and timing of multidimensional assessments in chronic obstructive pulmonary disease (COPD) remains unclear because there is little information about their variability and relationship to outcome. The aim of this study was to determine the progression of COPD using clinical and spirometric variability over time with mortality as the outcome. We determined the annual intra-individual variability of forced expiratory volume in 1 s (FEV1) and BODE (body mass index, airflow obstruction, dyspnoea, exercise capacity) index in 403 patients with at least five measurements. The pattern was defined as "stable" if the annual change remained constant in ≥66% of the observations and "unstable" if it did not meet that threshold. We explored the minimum number of yearly observations that related to mortality in the 704 patients of the cohort. The "unstable" pattern of FEV1 was seen in 53% and 40% of patients using a threshold of 40 mL·year(-1) and 100 mL·year(-1), respectively. There was a slightly more "stable" pattern in the BODE index (62% for 1 point). A profile associated with mortality was defined by a baseline measurement followed by annual measurements for 2 years of the BODE index, but not its individual components, including FEV1 (p<0.001). Progression of COPD measured using FEV1 is inconsistent and relates poorly to outcome. Monitoring the more stable BODE index better assesses disease progression.

The E180splice mutation in the GHR gene causing Laron syndrome: witness of a Sephardic Jewish exodus from the Iberian Peninsula to the New World?

Laron syndrome (LS) is a genetic disorder caused by mutations in the growth hormone receptor (GHR) gene. The most frequent GHR mutation is E180splice (rs121909360), which was initially found in an inbred population of Spanish descent in Ecuador and subsequently in Israel, Brazil, Chile, and the United States. The aim of the present study is to determine if the E180splice mutation arose from a common origin. We studied 22 patients with LS from Ecuador, Israel (of Moroccan origin), Brazil, Chile, and the United States (of Mexican origin) who were homozygous for the E180splice mutation and compared them to control individuals for markers surrounding the GHR, intragenic polymorphisms, and Y-chromosome STR. An identical haplotype was found in all but one of the subjects carrying the E180splice mutation: D5S665: 150/150; D5S2082: 192/192; D5S2087: 246/246; rs6179 G/G; and rs6180 C/C. One patient differed from the others only at D5S2082 (168/192). This haplotype is rare (~1%) in control individuals and confirmed that the E180splice-associated haplotype was not derived from independent origins but represented recombination from a common ancestor. The analysis of paternal lineage markers showed that 50% belong to haplogroup R1b (found in Portugal and Spain) and 40% to haplogroups J and E (typical in the Middle East and in Eastern European Jews). The germline E180Splice mutation appears to have originated from a single common ancestor. The presence of Y-chromosome markers associated with Sephardic populations in persons harboring the E180splice mutation provides genetic evidence in support of the historical tracking of the exodus of this specific population.

[Ecogeography of the genus Sticta (lichenized Ascomycota: Lobariaceae) in Colombia]. / Ecogeografía del género Sticta (Ascomycota liquenizados: Lobariaceae) en Colombia.

Colombia is a megadiverse country, but with a substantial gap in the taxonomic and ecological knowledge of fungi and lichens. Thus, the objective of the present study was an ecogeographical analysis of the Sticta species in Colombia. The data included macrodistribution (with respect to mountain ranges and life zones) and microhabitat preferences (light, substrate) and were obtained from field work and herbarium collection labels (completed by comparison with modern geographic and vegetation maps), for 103 species of Sticta currently recognized in Colombia (plus seven additional biotypes with different photobionts or reproductive mode). Using non-metric multidimensional scaling (NMS), correlations between ecogeographical variables and species were established, and ecotypes were delimited. Colombian species of Sticta showed distinct distribution patterns relative to altitude, mountain ranges, life zones, as well as light exposure and substrate, forming several distinct groups. Cyanobacterial species tend to have wider distribution ranges than green algal species. We concluded that the orogeny of the Northern Andes substantially affected speciation of the genus Sticta and its ecogeographical differentiation.