The impact of alpha-1 antitrypsin deficiency alleles on lung cancer survival.

Different studies have shown that carrying an alpha-1 antitrypsin (AAT) deficiency allele is an independent risk factor for developing lung cancer (LC). However, to date, little is known regarding whether carrying a deficiency allele may be a prognostic factor in the evolution of LC. A prospective observational study was carried out which consecutively included patients diagnosed with LC in University Hospital "Nuestra Señora de Candelaria" between December 2017 and August 2020. A blood sample was taken from each of the patients in order to determine both AAT serum concentration and genotype. Based on AAT genotype, patients were divided into the deficiency (Pi*≠MM) or non-deficiency (Pi*=MM) group. One hundred and sixty-four patients were included. The average length of follow-up was 13±10 months. Patients were classified as stage I (4.2%), stage II (8.3%), stage III (31.2%) and stage IV (56.3%), according to tumour, node and metastasis (TNM) staging. Twenty-eight patients (17%) were carriers of a deficiency allele (6 Pi*MS, 1 Pi*MZ, 1 Pi*MMheerlen). No significant differences were found with respect to baseline characteristics between Pi*≠MM and Pi*=MM. Patients in the Pi*≠MM group had a higher risk of death in the first 6 months after the LC diagnosis compared to Pi*=MM subjects (HR =2.04; 95% CI: 1.04-4.0; P=0.038). The presence of an AAT deficiency genotype could be a potential prognostic marker in LC. However, larger studies that justify these findings are needed.

Modulation of KV4.3-KChIP2 Channels by IQM-266: Role of DPP6 and KCNE2.

The transient outward potassium current (Itof) is generated by the activation of KV4 channels assembled with KChIP2 and other accessory subunits (DPP6 and KCNE2). To test the hypothesis that these subunits modify the channel pharmacology, we analyzed the electrophysiological effects of (3-(2-(3-phenoxyphenyl)acetamido)-2-naphthoic acid) (IQM-266), a new KChIP2 ligand, on the currents generated by KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 channels. CHO cells were transiently transfected with cDNAs codifying for different proteins (KV4.3/KChIP2, KV4.3/KChIP2/DPP6 or KV4.3/KChIP2/KCNE2), and the potassium currents were recorded using the whole-cell patch-clamp technique. IQM-266 decreased the maximum peak of KV4.3/KChIP2, KV4.3/KChIP2/DPP6 and KV4.3/KChIP2/KCNE2 currents, slowing their time course of inactivation in a concentration-, voltage-, time- and use-dependent manner. IQM-266 produced an increase in the charge in KV4.3/KChIP2 channels that was intensified when DPP6 was present and abolished in the presence of KCNE2. IQM-266 induced an activation unblocking effect during the application of trains of pulses to cells expressing KV4.3/KChIP2 and KV4.3/KChIP2/KCNE2, but not in KV4.3/KChIP2/DPP6 channels. Overall, all these results are consistent with a preferential IQM-266 binding to an active closed state of Kv4.3/KChIP2 and Kv4.3/KChIP2/KCNE2 channels, whereas in the presence of DPP6, IQM-266 binds preferentially to an inactivated state. In conclusion, DPP6 and KCNE2 modify the pharmacological response of KV4.3/KChIP2 channels to IQM-266.

Tratamiento de inicio en la enfermedad pulmonar obstructiva crónica, según GesEPOC 2021 vs. GesEPOC 2017, ¿acercando criterios con GOLD 2021? / Initial Treatment in Chronic Obstructive Pulmonary Disease According to GesEPOC 2021 vs. GesEPOC 2017. Approaching Criteria with GOLD 2021?

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[Translated article] Initial Treatment in Chronic Obstructive Pulmonary Disease According to GesEPOC 2021 vs. GesEPOC 2017. Approaching Criteria With GOLD 2021? / Tratamiento de inicio en la enfermedad pulmonar obstructiva crónica, según GesEPOC 2021 vs. GesEPOC 2017, ¿acercando criterios con GOLD 2021?

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Characteristics of patients referred to Canary Island pneumology outpatient services for chronic obstructive pulmonary disease: the EPOCan study.

OBJECTIVE: Assessing patients with chronic obstructive pulmonary disease (COPD) accounts for 30% of all pneumology outpatient evaluations. COPD is a heterogeneous disease and generates a massive public health problem. Overall morbidity, particularly cardiovascular disease, challenges patient management. This is an observational, multicentre study, performed at four hospitals in the Canary Islands (Spain), aimed at characterising patients with COPD referred to pneumology outpatient services. Demographic variables, lung function, and morbidity were assessed. RESULTS: Of the 877 included patients, 44.9% were active smokers with a mean (± SD) age of 68.2 ± 10.3 years. The median (IQR) score for the Charlson comorbidity index was 2 (2), and 70.6% of the patients were assigned high risk according to the Spanish Guidelines for COPD (GesEPOC) 2021. The degree of airflow obstruction defined by the GOLD 2021 stages 1, 2, 3, and 4 corresponded to 13.6%, 49%, 31%, and 6.3% of patients, respectively. The most frequently associated morbidities were arterial hypertension (59.5%), dyslipidaemia (54.3%), and type 2 diabetes mellitus (31.2%); 32% of the patients suffered heart disease. There is a high prevalence of active smoking, type 2 diabetes mellitus, and heart disease in patients referred for COPD to Canary Island pneumology outpatient services.

TRPM8 Channels: Advances in Structural Studies and Pharmacological Modulation.

The transient receptor potential melastatin subtype 8 (TRPM8) is a cold sensor in humans, activated by low temperatures (>10, <28 °C), but also a polymodal ion channel, stimulated by voltage, pressure, cooling compounds (menthol, icilin), and hyperosmolarity. An increased number of experimental results indicate the implication of TRPM8 channels in cold thermal transduction and pain detection, transmission, and maintenance in different tissues and organs. These channels also have a repercussion on different kinds of life-threatening tumors and other pathologies, which include urinary and respiratory tract dysfunctions, dry eye disease, and obesity. This compendium firstly covers newly described papers on the expression of TRPM8 channels and their correlation with pathological states. An overview on the structural knowledge, after cryo-electron microscopy success in solving different TRPM8 structures, as well as some insights obtained from mutagenesis studies, will follow. Most recently described families of TRPM8 modulators are also covered, along with a section of molecules that have reached clinical trials. To finalize, authors provide an outline of the potential prospects in the TRPM8 field.

Desire, envy and punishment: a Matsigenka emotion schema in illness narratives and folk stories.

Accumulating evidence suggests that folktales in some societies are characterized by a culturally constructed underlying emotional structure, or Cultural Emotion Schema. In this paper we argue that Matsigenka illness narratives and folk stories share an underlying emotion schema, in which death and suffering result from conflicts between strong-willed individuals prompting anger and aggression. Analysis of illness narratives collected by Izquierdo in the Matsigenka community of Kamisea in the Peruvian Amazon between 1996 and 1999 reveals a common pattern in which envy and frustration lead to the belief in sorcery as the main cause of illness and death. This pattern contrasts with the typical stories of a previous generation collected by the Johnsons among the Matsigenka of Shimaa and other Matsigenka researchers, where sorcery beliefs were virtually absent. Our argument is that important changes in ecology, community, politics, and religion have led to a systematic rise in feelings of envy and frustration, and that these have increased the likelihood that sorcery accusations will occur. We explore the likelihood that such beliefs increase as egalitarian peoples become more crowded into settlements where they are likely to experience greater inequality, more competition for resources and increased societal and personal stress.

When "health" is not enough: societal, individual and biomedical assessments of well-being among the Matsigenka of the Peruvian Amazon.

Although biomedical indicators of health status show that physical health for the Matsigenka of the Peruvian Amazon has significantly improved over the past 20-30 years, the Matsigenka perceive their health and well-being to have severely declined during this period. This discrepancy between empirical measures and local perceptions of health and well-being points to the central tension inherent in measuring and defining "health." While biomedical parameters of health are generally linked to notions of the body free of illness, measurable by physiological means, the Matsigenka define physical health as only one component of what it means to be healthy and to experience well-being. For the Matsigenka, notions of health and well-being are linked fundamentally to ideals about happiness, productivity and goodness, in addition to biomedical health. The Matsigenka attribute the decrease in their well-being to newly instigated sorcery and stressors resulting from outside influences and morality institutionalized by cultural "outsiders", such as missionaries, school teachers, health personnel, oil company employees and government officials. This article explores the relationships between biomedical, societal and personal assessments of health and well-being among the Matsigenka as they seek to preserve their sense of wellness in spite of their rapidly changing social and economic environment. By using longitudinal qualitative and quantitative ethnographic and health data, this paper shows that, for the Matsigenka, increases in acculturation and permanent settlement result in an alarming decrease in their health and well-being.