[Lung cancer at a Chilean public hospital]. / Cáncer pulmonar: caracterización, estadificación y supervivencia en una cohorte de una década en un hospital del sistema público de salud de Chile.

BACKGROUND: Lung cancer is the world's leading cause of cancer death. AIM: To describe the clinical, staging and survival characteristics of lung cancer in a public Chilean regional hospital. MATERIAL AND METHODS: Analysis of a prospective database of a thoracic surgery service, retrieving histologically confirmed lung cancer cases from January 2010 to December 2019 and reviewing their medical records. Cases were re-staged by the TNM-8 system and variables were compared between periods 2010-2014 and 2015-2019. RESULTS: We retrieved 551 lung cancer cases, 333 (60 %) men, with a mean age of 65 years. Distant metastases were found in 72% of cases (excluding lymphatic metastases). Of the non-small cell lung cancers (NSCLC), 50 (10%) cases were in stage I, 18 (4%) in stage II, 81 (16%) in stage III and 347 (70%) in stage IV. Global five-year survival was 18%, 20% for NSCLC, 71% for excised NSCLC, 8% for non-excised NSCLC, 88% for stage I and 92% for subgroup IA. Resective surgery was performed in 81 (14%) cases. When comparing 2010-2014 and 2015-2019 periods, the frequency of resective surgery increased from 7% to 20%. CONCLUSIONS: The diagnosis of lung cancer was frequently made in advanced stages. There was a significant increase in early diagnosis and frequency of surgeries with curative intent in the second observation period.

Polymorphisms and haplotypes of the interleukin 2 gene are associated with an increased risk of gastric cancer. The possible involvement of Helicobacter pylori.

Interleukin 2 (IL-2) is a pro-inflammatory cytokine that is mainly synthesized by immunoregulatory T helper cells and which plays an important role in antitumor immunity. Helicobacter pylori (H. pylori) is a gram-negative bacterium that colonizes the gastric mucosa and induces the production of IL-2. This process increases the magnitude of inflammation and may influence the development of gastric pathologies. In light of the possible involvement of IL-2 and the presence of H. pylori in gastric diseases, this study investigated possible associations between the IL-2 polymorphisms +114 T>G (rs2069763) and -330 T>G (rs2069762) and the development of gastric cancer; these associations were then correlated with the presence of H. pylori. Gastric biopsies were obtained from 294 dyspeptic patients (173♀/123♂). Of these samples, 181 were chronic gastritis samples (102♀/79), 62 were samples of intact gastric mucosa (47♀/15♂), and 51 were samples of gastric cancer (22♀/29♂). PCR-RFLP was used to characterize the +114 T>G and -330 T>G polymorphisms. Considering the genetic characteristics of the study population and based on the codominant model, a high risk of gastric cancer among patients with normal gastric tissue and patients with gastric cancer was found in subjects with the IL-2-330 GG genotype (OR=6.43, 95% CI: 1.47-28.10, p=0.044). The data was adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found among subjects with the IL-2-330 GG genotype (OR=4.47, 95% CI: 1.84-10.84, p=0.0022). When the IL-2 +114 polymorphism was analyzed, similar results were found. Among the patients with normal gastric tissue and the patients with gastric cancer, subjects carrying the +114 TT genotype were found to be at a high risk of gastric cancer (OR=5.97, 95% CI: 1.60-22.27, p=0.013). This data was also adjusted for the presence of H. pylori. Among patients with gastritis and patients with gastric cancer, a high risk was found in subjects carrying the +114 TT genotype (OR=6.36, 95% CI: 2.66-15.21, p<0.0001). The haplotype was also analyzed. The -330G/+114T haplotype was found to be significantly associated with gastric cancer. Therefore, our results show that, among patients with H. pylori infection, the -330 GG and +114 TT genotypes are significantly associated with a high risk of developing gastric cancer, as is the -330G/+114T haplotype.

Maintaining benefits following pulmonary rehabilitation: a randomised controlled trial.

The aim of this study was to determine if weekly, supervised, outpatient-based exercise plus unsupervised home exercise following an 8-week pulmonary rehabilitation programme would maintain functional exercise capacity and quality of life at 12 months better than standard care of unsupervised home exercise training. Chronic obstructive pulmonary disease (COPD) subjects completed an 8-week pulmonary rehabilitation programme, were randomised to an intervention group (IG) of weekly, supervised, exercise plus home exercise or to a control group (CG) of unsupervised home exercise and followed for 12 months. Outcome measurements at baseline (after pulmonary rehabilitation), and 3, 6 and 12 months included the 6-min walk test and St George's Respiratory Questionnaire (SGRQ). 59 subjects with moderate COPD (Global Initiative for Chronic Obstructive Lung Disease stage II) were recruited and 48 subjects completed the study. 12-month mean difference showed no significant change from baseline in 6-min walk distance (IG -11 m, 95% CI -21-10 m; CG -6 m, 95% CI -34-11 m) or total SGRQ score (IG 3, 95% CI -0.8-7; CG -3, 95% CI -7-3). 12 months following pulmonary rehabilitation both weekly, supervised, outpatient-based exercise plus unsupervised home exercise and standard care of unsupervised home exercise successfully maintained 6-min walk distance and quality of life in subjects with moderate COPD.

Characterization of Cerebellum-Specific Ribosomal DNA Epigenetic Modifications in Alzheimer's Disease: Should the Cerebellum Serve as a Control Tissue After All?

Alzheimer's disease (AD) is a neurodegenerative disease, known as the most common form of dementia. In AD onset, abnormal rRNA expression has been reported to be linked in pathogenesis. Although region-specific expression patterns have previously been reported in AD, it is not until recently that the cerebellum has come under the spotlight. Specifically, it is unclear whether DNA methylation is the mechanism involved in rRNA expression regulation in AD. Hence, we sought to explore the rDNA methylation pattern of two different brain regions - auditory cortex and cerebellum - from AD and age-/sex-matched controls. Our results showed differential hypermethylation at an upstream CpG region to the rDNA promoter when comparing cerebellum controls to auditory cortex controls. This suggests a possible regulatory region from rDNA expression regulation. Moreover, when comparing between AD and control cerebellum samples, we observed hypermethylation of the rDNA promoter region as well as an increase in rDNA content. In addition, we also observed increased rRNA levels in AD compared to control cerebellum. Although still considered a pathology-free brain region, there are growing findings that continue to suggest otherwise. Indeed, cerebellum from AD has been recently described as affected by the disease, presenting a unique pattern of molecular alterations. Given that we observed that increased rDNA promoter methylation did not silence rDNA gene expression, we suggest that rDNA promoter hypermethylation is playing a protective role in rDNA genomic stability and, therefore, increasing rRNA levels in AD cerebellum.

Hip extension power and abduction power asymmetry as independent predictors of walking speed in individuals with unilateral lower-limb amputation.

BACKGROUND: Preferred walking speed (PWS) is an indicator of walking ability, prosthetic walking potential, and function following a lower-limb amputation (LLA). There is a link between lower-limb muscle performance and PWS in individuals with LLA. However, the ability of select hip muscle performance parameters to determine PWS in these individuals still needs to be thoroughly investigated. RESEARCH QUESTION: Which hip muscle and joint torque parameters best determine PWS in persons with LLA? METHODS: Seventeen patients with LLA (6 transfemoral, 4 knee disarticulation, and 7 transtibial; 16 men, 1 woman; mean age ± standard deviation, 56 ± 15yr) participated in this cross-sectional study. Maximal joint torque and power were evaluated unilaterally, for both amputated and intact limbs, in isometric and isokinetic conditions during hip flexion/extension (60°/s and 180°/s) and abduction/adduction (30°/s and 90°/s). PWS was measured at habitual walking speed over a 10-m distance. Pearson's correlation coefficient was used to verify the degree of association between each torque parameter and PWS and multiple regression analysis was performed to identify the best predictors of PWS. The level of significance was p < 0.05. RESULTS: Correlations between hip muscle performance parameters and PWS were found in most cases (r = 0.51-0.82; p ≤ 0.036-0.0005). The multiple regression model revealed that the best independent predictors of PWS were hip extension power at 180°/s on the amputated side (r² = 0.672; p < 0.0005) and the asymmetry of hip abduction power at 30°/s (r² = -0.147; p < 0.008), accounting together for 82% of the variance in PWS. SIGNIFICANCE: Lesser hip extension power on the amputated side and greater hip abduction power asymmetry between limbs are detrimental to PWS in persons with LLA. These muscle groups and performance parameters should be considered during gait rehabilitation to assist individuals with LLA in achieving functional waking speed.

CDK5 and MAPT Gene Expression in Alzheimer's Disease Brain Samples.

BACKGROUND: Alzheimer's disease (AD) is a neurodegenerative disorder characterized by extracellular amyloid plaque and neurofibrillary tangles in the brain. Studies have shown that neurons are able to re-enter the cell cycle, but not enough to enable full replication. This leads to cell death and consequent neurodegeneration. OBJECTIVE: This study aimed to characterize the expression of the MAPT gene and CDK5 (the gene involved in cell cycle regulation) in brain samples from patients with AD and controls. METHOD: The real-time-PCR technique was used to characterize 150 samples from three areas of the brain (entorhinal cortex, auditory cortex, and hippocampus) of 26 AD patients and 24 healthy elderly subjects. RESULTS: When the brain samples were analyzed collectively, a decrease in CDK5 and MAPT gene expression was found in AD patients. When each groups' samples were separated by area of the brain and compared, significant differences were found in CDK5 expression in the hippocampus and the entorhinal cortex. In both cases, mRNA was lower in the AD group (p=0.0001); however, the same analysis using the MAPT gene revealed no significant statistical differences. No statistical differences were found when gene expression was compared between the different regions of the brain within each group. CONCLUSION: These results may contribute to a better understanding of the involvement of CDK5 and MAPT genes in AD in that they consider different areas of the brain that are affected differently based on disease progression. The main challenge is to establish an effective therapy for this debilitating disease in the future.

Change in INSR, APBA2 and IDE Gene Expressions in Brains of Alzheimer's Disease Patients.

BACKGROUND: Alzheimer's disease (AD) is defined as a progressive and irreversible neurodegenerative disorder, the onset of which is mainly characterized by decreased cognition, memory loss, and mental confusion. OBJECTIVE: This study sought to quantify mRNA expression of the APBA2, INSR and IDE genes in brain samples from patients with AD and controls. METHODS: We investigated the mRNA expression of the APBA2, INSR and IDE genes in 150 RNA samples from entorhinal cortex, auditory cortex, and the hippocampus of individuals with AD and elderly controls using real time PCR. APOE genotypes were determined by PCR-RFLP. RESULTS: When the total brain samples were analyzed collectively, a decrease in IDE gene expression was found in AD patients relative to healthy elderly controls. However, when the samples were analyzed separately according to the region of the brain, there was a significant upregulation of INSR expression in the hippocampus and the entorhinal cortex in the AD patient group. We did not observe any statistical differences when gene expression was compared in the different regions of the brain of AD patients. When the E4 allele of apolipoprotein-E was considered in AD patients, the presence of this allele was found to be associated with decreased APBA2 gene expression. The same analysis using the INSR and IDE genes showed no significant statistical differences. CONCLUSION: These results support the hypothesis that APBA2, IDE, and particularly INSR gene expression in different areas of Alzheimer's patient's brains could represent new markers for use in clinical diagnoses in the near future.

Cáncer pulmonar: caracterización, estadificación y supervivencia en una cohorte de una década en un hospital del sistema público de salud de Chile / Lung cancer at a Chilean public hospital

Background: Lung cancer is the world's leading cause of cancer death. Aim: To describe the clinical, staging and survival characteristics of lung cancer in a public Chilean regional hospital. Material and Methods: Analysis of a prospective database of a thoracic surgery service, retrieving histologically confirmed lung cancer cases from January 2010 to December 2019 and reviewing their medical records. Cases were re-staged by the TNM-8 system and variables were compared between periods 2010-2014 and 2015-2019. Results: We retrieved 551 lung cancer cases, 333 (60 %) men, with a mean age of 65 years. Distant metastases were found in 72% of cases (excluding lymphatic metastases). Of the non-small cell lung cancers (NSCLC), 50 (10%) cases were in stage I, 18 (4%) in stage II, 81 (16%) in stage III and 347 (70%) in stage IV. Global five-year survival was 18%, 20% for NSCLC, 71% for excised NSCLC, 8% for non-excised NSCLC, 88% for stage I and 92% for subgroup IA. Resective surgery was performed in 81 (14%) cases. When comparing 2010-2014 and 2015-2019 periods, the frequency of resective surgery increased from 7% to 20%. Conclusions: The diagnosis of lung cancer was frequently made in advanced stages. There was a significant increase in early diagnosis and frequency of surgeries with curative intent in the second observation period.

Differential Expression of Ribosomal Genes in Brain and Blood of Alzheimer's Disease Patients.

Changes in rRNA and rDNA expression have been associated with cellular and organism aging and have been linked to Alzheimer's disease (AD) pathogenesis. In this study, we investigated the mRNA expression of ribosomal genes (28S/18S) and ß-amyloid precursor protein (APP) in different post mortem brain tissue regions (the entorhinal and auditory cortices and the hippocampus) of AD patients and elderly control subjects and also evaluated the extent of expression in peripheral blood from young, healthy, elderly, and Alzheimer's disease patients in order to investigate whether these individuals experienced the effects of aging. The comparative threshold cycle (CT) method via Real Time Polymerase Chain Reaction and the Polymerase Chain Reaction- Restriction Fragment Length Polymorphism (PCR-RFLP) were used to analyze gene expression and the Apolipoprotein E (APOE) genotype, respectively. When the brain areas were analyzed collectively, we observed a significant decrease in APP expression and a significant increase in levels of mRNA of 18S and 28S in Alzheimer's disease patients compared to healthy elderly individuals. Furthermore, there was a significant upregulation of 28SrRNA in the entorhinal cortex and hippocampus, but not in the auditory cortex of patients with AD. On the other hand, tests of blood samples verified a decreased expression of 28S rRNA in patients with AD. These results support the hypothesis that changes in rRNA are present in AD patients, are tissue-specific, and seem to occur independently and differently in each tissue. However, the next challenge is to discover the mechanisms responsible for the differences in expression observed in the blood and the brain in both healthy elderly individuals and Alzheimer's disease patients, as well as the impact of these genes on AD pathogenesis.

Orchidectomy enhances the expression of endothelin-1 and ETB receptors in rat portal vein.

Functional studies have shown that orchidectomy increases the effects of phenylephrine on rat portal veins, but that it is completely prevented in the presence of both ETA and ETB receptor antagonists. Although it suggests the involvement of endothelin-1 (ET-1), the local production of this vasoactive peptide has not been directly quantified in portal veins. Therefore, the aim of the present study was to verify if orchidectomy increases the local expression of ET-1 as well as ETA and ETB receptors in the rat portal vein. Indeed, the genic expression of ET-1, ETA and ETB receptors in rat portal veins taken from control (CONT), orchidectomized (ORX) and ORX plus testosterone-replacement therapy (ORX + T) animals were determined by Real Time RT-PCR. The results showed that orchidectomy induced a significant increment in genic expression of ET-1 and ETB receptors in the rat portal veins, which was completely reversed by testosterone replacement treatment. In conclusion, the results suggest that orchidectomy increases the production of ET-1 in the rat portal vein and that, at least partially, it may be related to the previously reported elevation of responses to phenylephrine.