The cardiovascular disease burden attributable to particulate matter pollution in South America: analysis of the 1990-2019 global burden of disease.

OBJECTIVES: Fine particulate matter <2.5 microns (PM2.5) is the most studied air pollutant. Both short- and long-term exposure to PM2.5 have been linked to cardiovascular disease (CVD). Studies evaluating air pollution in South America are scarce. Therefore, the impact of exposure to PM2.5, household air pollution (HAP), and ambient air pollution (AAP) on CVD mortality and CVD disability-adjusted life years (DALYs) in South American countries from 1990 to 2019 was explored. STUDY DESIGN AND METHODS: The Global Burden of Disease initiative exposure-response function was used to analyze the total PM2.5, ambient PM2.5, and household PM2.5-related CVD deaths and DALYs rates, per 100,000 individuals, in 12 South American countries between 1990 and 2019. The relative change in burden was also assessed by comparing the 1990-1994 to 2015-2019 periods. RESULTS: In 2019, 70,668 deaths and 1,736,414 DALYs due to CVD were attributed to total PM2.5 exposure in South America. Substantial regional heterogeneity was observed concerning the absolute change in PM2.5 concentration levels comparing 1990 to 2019. All South American countries observed a relative decline in CVD deaths and DALYs comparing the 1990-1994 to 2015-2019 periods. No country was able to reach the current World Health Organization 5 µg/m3 recommended limit in 2019. Predominantly, AAP was the greatest contributor to the CVD burden. CONCLUSION: Air pollution substantially impacted CVD in South America; however, this impact was heterogenous, and the relative reduction of HAP and AAP burden was also not uniform. Recognizing PM2.5 importance is key for developing target population and individual-level interventions, which could ultimately alleviate its burden.

Central versus peripheral arterial cannulation and neurological outcomes after thoracic aortic surgery: meta-analysis and meta-regression of 4459 patients.

BACKGROUND: Thoracic aortic surgeries remain with high mortality rates, often associated with postoperative neurological complications. The choice of the right cannulation site is extremely important for suitable blood supply and maintenance of vital functions, especially of the central nervous system. OBJECTIVES: To compare the influence of central versus peripheral arterial cannulation on neurological outcomes in patients undergoing thoracic aortic surgery through systematic review and meta-analysis. METHODS: MEDLINE, EMBASE, CENTRAL/CCTR, SciELO, LILACS and reference lists of relevant articles were searched for clinical studies that reported in-hospital neurological outcomes after central or peripheral arterial cannulation during thoracic aortic surgery procedures until December 2013. The principal summary measures were Odds Ratio (OR) for central compared to peripheral arterial cannulation with 95% confidence interval (CI) and p-values considered statistically significant when <0.05. The ORs were combined across studies, using the DerSimonian-Laird random effects model and fixed effects model using the Mantel-Haenszel model--both models were weighted. The meta-analysis was completed using the software Comprehensive Meta-Analysis version 2 (Biostat Inc., Englewood, NJ). RESULTS: Six studies were identified and included a total of 4459 patients (1180 for central and 3279 for peripheral cannulation). There was no significant difference between the central and peripheral groups regarding neurological outcomes. The meta-regression evidenced no relationship between neurological outcomes and the variables age, sex, previous coronary event, previous neurological event, urgency surgery, cardiopulmonary bypass time, activated clotting time and esophageal temperature with p > 0,05. CONCLUSION: When it comes to neurological outcomes in patients undergoing thoracic aortic surgery, there was no evidence that argues in favor of any choice of arterial cannulation site, which makes us reject any superiority of one approach over the other in this regard.

Recent evolutionary history of Lost World endemics: population genetics, species delimitation, and phylogeography of sky-island treefrogs.

The tepuis of South America are massive flattop mountains with cliffs up to 1000m and summits up to 3100m. Tepuis hold enormous endemicity levels, but little is known about the origins of the endemic flora and fauna. Recently diverged lineages offer the possibility of understanding the origins of summit endemicity by examining population dynamics and dispersal. We examine species delimitation, clade relationships, and demographic patterns of three recently diverged lineages of Tepuihyla, an endemic treefrog clade. These three lineages represent two currently recognized species, T. edelcae and T. rodriguezi. Given the low divergences in both nuclear and mitochondrial genes among lineages, we find unexpectedly high numbers of unique nuclear haplotypes and moderate levels of lineage sorting. We also find support from multiple analyses for a cryptic, undescribed summit species within T. edelcae. We suggest that the genetic and distribution patterns of the four most recently diverged Tepuihyla lineages support a concurrent speciation event during the Pliocene, and suggest a biogeographic hypothesis in which a widespread climatic change made mid- and low-elevation habitat unsuitable for the common ancestor within the timeframe of their divergence.

CD97 amplifies LPA receptor signaling and promotes thyroid cancer progression in a mouse model.

CD97, a member of the adhesion family of G-protein-coupled receptors (GPCRs), complexes with and potentiates lysophosphatidic acid (LPA) receptor signaling to the downstream effector RHOA. We show here that CD97 was expressed in a majority of thyroid cancers but not normal thyroid epithelium and that the level of CD97 expression was further elevated with progression to poorly differentiated and undifferentiated carcinoma. Intratumoral progression also showed that CD97 expression correlates with invasiveness and dedifferentiation. To determine the functional role of CD97, we produced a transgenic model of thyroglobulin promoter-driven CD97 expression. Transgenic CD97 in combination with Thrb(PV), an established mouse model of thyroid follicular cell carcinogenesis, significantly increased the occurrence of vascular invasion and lung metastasis. Expression of transgenic CD97 in thyroid epithelium led to elevated ERK phosphorylation and increased numbers of Ki67+ cells in developing tumors. In addition, tumor cell cultures derived from CD97 transgenic as compared with non-transgenic mice demonstrated enhanced, constitutive and LPA-stimulated ERK activation. In human thyroid cancer cell lines, CD97 depletion reduced RHO-GTP and decreased LPA-stimulated invasion but not EGF-stimulated invasion, further suggesting that CD97 influences an LPA-associated mechanism of progression. Consistent with the above, CD97 expression in human thyroid cancers correlated with LPA receptor and markers of aggressiveness including Ki67 and pAKT. This study shows an autonomous effect of CD97 on thyroid cancer progression and supports the investigation of this GPCR as a therapeutic target for these cancers.

A set of miRNAs participates in the cellular senescence program in human diploid fibroblasts.

Here we show that replicative senescence in normal human diploid IMR90 fibroblasts is accompanied by altered expression of a set of microRNAs (miRNAs) (senescence-associated miRNAs), with 14 and 10 miRNAs being either up or downregulated (>2-fold), respectively, in senescent with respect to young cells. The expression of most of these miRNAs was also deregulated upon senescence induced by DNA damage (etoposide) or mild oxidative stress (diethylmaleate). Four downregulated miRNAs were part of miRNA family-17, recently associated to human cell and tissue aging. Moreover, eight upregulated and six downregulated miRNAs mapped in specific chromosomal clusters, suggesting common transcriptional regulation. Upon adoptive overexpression, seven upregulated miRNAs induced the formation of senescence-associated heterochromatin foci and senescence-associated ß-galactosidase staining (P<0.05), which was accompanied, in the case of five of them, by reduced cell proliferation. Finally, miR-210, miR-376a(*), miR-486-5p, miR-494, and miR-542-5p induced double-strand DNA breaks and reactive oxygen species accumulation in transfected cells. In conclusion, we have identified a set of human miRNAs induced during replicative and chemically induced senescence that are able to foster the senescent phenotype by prompting DNA damage.

[Folic acid and congenital malformation: scientific evidence and public health strategies]. / Acido folico e difetti congeniti: evidenze scientifiche e strategie di sanità pubblica.

In Italy at least 3% of babies are born with some congenital malformation. The intake of folic acid (FA) prior to conception and during the early stages of pregnancy plays an important role in preventing neural tube defects, severe anomalies of brain embryogenesis, and other malformations such as cardiac and urinary tract anomalies, oro-facial clefts and limb reduction defects. The Italian Network for Folic Acid Promotion, coordinated by the National Center on Rare Diseases of the Italian National Institute of Health, has elaborated and diffused a recommendation for the periconceptional FA supplementation: "Women of child-bearing age, are recommended to consume 0,4 mg/day of FA, to reduce the risk of congenital defects. The intake of folic acid should start at least one month before the conception and should continue for the first quarter of pregnancy". This paper discusses various strategies in order to promote FA intake during periconceptional period. Food fortification, adopted in several countries such as USA, has raised concerns about the risk of an excessive FA intake which may lead to adverse effect such as tumour promotion. Currently, periconceptional supplementation and healthy dietary habits promotion appear to be the most effective strategies.

Access to and quality of health and social care for rare diseases: patients' and caregivers' experiences.

People suffering from rare diseases, independently of the condition, often experience the same problems in receiving adequate health and social care. It is not clear how these problems differ in severity among different diseases and in different countries and how they change in time. In the framework of the NEPHIRD (Network of Public Health Institutions on Rare Diseases), a European project, funded by DG-SANCO (EU Commission), an effort was made to develop a simple but comprehensive tool to show patients' and/or caregivers' opinions about the quality and accessibility of health and social services. The self-filled questionnaire asks how often patients or caregivers had both negative and positive experiences about the quality and accessibility of health and social services and their opinion on their improvement, on 5-level scales. A pilot survey was carried out in several European Countries among members of Myasthenia Gravis, Neurofibromatosis, Prader Willi and Rett Syndrome volunteers' associations. Descriptive and comparative analyses were performed using Stata and Epi Info 2000. In total, 302 questionnaires were completed in France, Italy, Romania, Spain, Turkey and United Kingdom during 2004-05. In general, respondents thought that health care accessibility was worse than quality, and that social care and legal provisions were worse than health care, with some differences among countries. For all diseases, and for both patients and caregivers, the most frequent reported positive experiences were health professionals' kindness and readiness to help (all medians ranged from 3 to 5). As for the efforts for improvement made by public services in the last three years, the opinions were generally favourable. This study has several limitations. However the assessment tool that has been developed has some innovative and interesting features and may be considered a useful attempt to compare patients' and caregivers' experiences for a range of different diseases, countries and services, with respect to a rare disease programme.

[Accessibility and quality of Italian health and social services: the experiences of patients with neurofibromatosis type 1 and of their relatives]. / Accessibilità e qualità dei servizi socio-sanitari italiani: le esperienze dei pazienti con neurofibromatosi tipo 1 e dei loro familiari.

Opinions of patients and relatives about their experiences with health and social services were assessed in a pilot study. The study was carried out in collaboration with two patients' Associations of Neurofibromatosis, "Neurofibromatosi--Onlus" and "LINFA--Onlus". An ad-hoc questionnaire was developed by the Italian National Centre of Rare Diseases and was sent to the Responsibles of the two aforementioned patients' Associations. The Responsibles distributed the questionnaire to their members by mail. The questionnaire investigated, using 5-level Likert scales, the following topics: quality and accessibility of health services (diagnostic exams, pharmacological therapies, rehabilitation, psychological support), quality and accessibility of social services (school, vocational training, health information, information on legal matters and rights). Finally, the questionnaire investigated also opinions about improvements of public health and social services in the last three years. Overall, 79 out 144 questionnaires were filled by patients or their relatives. The most frequent negative experiences concerned vocational training and both health and legal information. The most frequent positive opinions were reported for the human relationships with health professionals. This pilot study seems to point out a promising way to investigate systematically opinions of patients suffering from rare diseases and their relatives.

[Accessibility and quality to health social services in Italy for the patients with rare diseases: the opinion of associations]. / Accessibilità e qualita dei servizi socio-sanitari italiani per i pazienti con malattie rare: il parere delle associazioni.

This paper concerns the first phase of a study about the perception of social and health needs of people with rare diseases. The study was performed by the National Center for Rare Diseases at the Italian National Institute of Health (Istituto Superiore di Sanità - ISS). The project wants to be an example of collaboration between the research and the association worlds. Responsible of Associations of Patients and their relatives were asked their opinion about the accessibility and quality of important features of health and social services (accessibility and quality of diagnostic, pharmacological, psychological and rehabilitative interventions, social support, school and vocational training, information that was given to relatives). An ad hoc questionnaire was developed through focus groups. The questionnaire was completed by 108 associations (26,5% of the associations thar are recorded in the ISS database). Average scores showed satisfaction only for some variables and a negative gradient north-south was observed. The most frequent complaints were about information, quality of school and job training services and availability of psychological support. The study showed an high level of dissatisfaction with availability, quality and integration health and social services.

[Opinions and attitudes on oral cancer in a sample of students attending a state secondary school in Rome. A pilot study]. / Opinioni e attitudini sul cancro della bocca in un campione di studenti di un liceo romano. Uno studio pilota.

BACKGROUND: This study aimed to evaluate knowledge and awareness in a group of secondary school students on the subject of risk factors and strategies used in the prevention of oral cancer. METHODS: The study took the form of a questionnaire which was filled in by a group of 106 secondary school students. The questionnaire was divided into 3 sections: the first analysed the general characteristics of the sample population; the second investigated their knowledge on the specific subject of this study; the last regarded exposure to risk factors and the role played by the dentist and family doctor in the prevention of oral cancer. RESULTS: Of the 106 students taking part in the study, 42% were male and 58% female. 30% of the group felt it was not possible to prevent cancer in general. 6% associated cigarette smoking with oral cancer, whereas 15% identified alcohol as a risk factor for the same pathology. 30% of the group thought that it was not possible to prevent oral cancer. In the event of a suspected oral lesion, 44% would consult the family doctor, 25% would go to the dentist and 3% to a dental technician. CONCLUSIONS: This study highlights the need improve knowledge of prevention methods in oral cancer. Although young people do not have a high risk of developing oral cancer, they represent a means of conveying information in a social and familial context, thus enabling an early diagnosis, and they also represent the preferred target for primary prevention activities.

[Anti-HBV vaccination and continuing education of health personnel: proposal for a priority index in various hospital units]. / Vaccinazione anti-HBV ed aggiornamento negli operatori sanitari: proposta di un indice delle priorità in diversi reparti ospedalieri.

This work defines an "hazard index of unit" for the occupational transmission of the HBV to the aim to establish the priorities in the activity of promotion of the hepatitis B vaccine turned to health personnel. It has been estimated the prevalence of the potentiality infecting for the HBV in patients coming to various unit and the cover immunization against HBV in personnel and used the incidence of exposures to biological risk, always reported to the single units, found in the within of the activity of the Committee of Control of the Hospitals infections in our hospital. The analysis evidences three areas to risk: infectious diseases, general surgery and obstetrics and gynecology.

Is it necrotizing enterocolitis, microcolon of prematurity, or delayed meconium plug? A dilemma in the tiny premature infant.

Failure of a small premature newborn to adequately evacuate meconium for days or weeks has been attributed to "probable necrotizing enterocolitis (NEC)" or "microcolon of prematurity." The authors present an unusual type of "meconium plug syndrome" with the same clinical picture, seen in tiny premature babies (500 to 1,500 g), which required a contrast enema or Gastrografin upper gastrointestinal (UGI) series to evacuate the plugs. The obstruction resolved. Twenty babies (480 to 1,500 g) presented with the same clinical picture without any x-ray suggestion of NEC; contrast enemas were performed because of the suspicion of meconium plug syndrome. All 20 had extensive meconium plugs that were evacuated by the enema or by a Gastrografin UGI series. Most of them improved after the plugs were passed. These infants differ from typical full-term babies with meconium plug syndrome in a number of ways: (1) many of the mothers were on magnesium sulfate (MgSO4) or had eclampsia; (2) the plugs were diagnosed late rather than shortly after birth; and (3) the plugs were significant, extending to the right colon. The authors believe that when a tiny premature baby has findings consistent with meconium plug syndrome, the baby should be transported to radiology, for a Gastrografin enema, despite the difficulties involved. Delay postpones the start of feedings, and increases the number of radiographic studies.

[Tempered composite resins in Ellis Class II fractures]. / Le resine composite temperate nelle fratture di II Classe di Ellis.

The Authors present a new method to improve the characteristics of the sandwich technique for the treatment of Ellis second class fracture.

Feasibility of pulmonary artery balloon counterpulsation via the percutaneous route: pathological studies on the heart and lungs.

The efficacy of pulmonary artery balloon counterpulsation (PABC) has been previously demonstrated. Clinically this is usually achieved by suturing a Dacron graft to the side of the pulmonary artery with an intra-aortic balloon pulsating inside the graft. PABC via the percutaneous route has not been previously reported, although it has been demonstrated experimentally that an intrapulmonary artery balloon inserted via the outflow of the right ventricle provides effective counterpulsation. The morphologic effects of PABC on the heart and lungs have not been previously demonstrated. This study evaluates the feasibility of PABC via the percutaneous route and assesses the morphologic changes of PABC on the heart and lungs of pigs. Results indicate that PABC via the percutaneous route is technically feasible. However, after 24 h of PABC morphologic changes occurred in the heart and lungs, consisting of valvular and mural thrombi and hemorrhage. Histopathologic evaluation of the lungs revealed interstitial and intra-alveolar hemorrhage and pulmonary emboli. The etiology of these pathologic changes are likely multifactorial. Further studies are necessary to fully delineate the short and long term effects of PABC prior to initiation of clinical trials with this new percutaneous assist device.

The effect of female serum antisperm antibodies on in vitro fertilization and embryo transfer.

Twenty-nine women with serum antisperm antibodies underwent in vitro fertilization and embryo transfer. Half the oocytes from each patient were treated with patient-serum-supplemented medium with antibodies (medium A), and the other half with donor-serum-supplemented medium without antibodies (medium B). In 9 cases the antibodies were against the sperm head and these showed a significant difference in the number of embryos obtained between the two media (p = 0.001): 10.5% of fertilization of type 3 and/or 4 oocytes with medium A and 81.2% with medium B. A lower rate resulted also when the antibodies were against the middle and main portion of the tail, but fertilization did not seem to be affected when they were directed against the tail tip. No definite conclusions are possible, however, since the number of cases studied was too small.

One year's experience with the GIFT method.

From January 1985 to December 1985 we have performed 83 GIFTS for various indications such as unexplained infertility, immunological problems, endometriosis, male factor, fimbrial pathology. In 82 women out of 83, oocytes and sperm have been transferred and 31 pregnancies (37.8%) have been obtained. Twelve women have delivered 17 babies; 11 pregnancies are ongoing, 7 have been interrupted by an abortion and 1 by a tubal pregnancy. The present and future roles of GIFT in the treatment of infertility is discussed.

Gamete intra-fallopian transfer (GIFT): a new technique for the treatment of unexplained infertility.

The Gamete Intrafallopian Transfer (GIFT) was carried out in 12 couples with unexplained infertility, in 2 cases with infertility associated with mild endometriosis, in 1 case of hostile mucus and 3 cases in which phymosis of the ampulla and/or periadnexal adhesions were previously identified. In 7 couples GIFT was carried out after several AID cycles for husband azoospermia or severe oligospermia. Three different protocols were used for the controlled ovarian hyperstimulation. In all cases an adequate follicular growth was obtained and mature oocytes were recovered. At first attempt 12 ongoing pregnancies (1 triplet, 1 twin) were obtained with a present pregnancy rate of 48%.

[Sleep in progressive supranuclear palsy]. / Il sonno nella paralisi sopranucleare progressiva.

Nocturnal sleep was poligraphycally recorded in three male patients aged 54-67, with progressive supranuclear palsy (PSP). All patients suffered from insomnia. In case 1 REM sleep was markedly reduced and spindles were less numerous than in normal subjects. In cases 2 and 3, EEG patterns were not distinguishable from those observed when the patients were awake. Sleep, therefore, was recognized only by constant observation of the patients. As seen in the literature EEG changes during sleep can be correlated to the severity of the clinical picture and the stage of evolution of the disease. EEG patterns of sleep in PSP are similar to those reported in patients with presenile dementia.