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Restorative proctocolectomy with ileal pouch-anal anastomosis is a treatment option for patients with refractory ulcerative colitis. Pouchitis is the most common complication, representing a spectrum of diseases ranging from acute antibiotic-responsive type to chronic antibiotic-refractory. Early accurate diagnosis using a combined assessment of symptoms, endoscopy and histology is important for both treatment and prognostication. Most patients respond well to antibiotic therapy; however, management of chronic antibiotic-refractory pouchitis remains a challenge, and treatment options are based on small studies. Pouchitis is thought to be driven by the interaction between genetics, the immune system and the environment but as yet a causal relationship has yet to be identified. Further longitudinal assessment of the pouch integrating new technologies may help us understand the factors driving pouchitis. This review outlines the currently understood risk factors and aetiology of pouchitis. [ABSTRACT FROM AUTHOR]

Background: Microtia is reported to be one of the most common congenital craniofacial malformations. Due to the complex etiology and the ethical barrier of embryonic study, the precise mechanisms of microtia remain unclear. Here we report a rare case of microtia with costal chondrodysplasia based on bioinformatics analysis and further verifications on other sporadic microtia patients. Results: One hundred fourteen deleterious insert and deletion (InDel) and 646 deleterious SNPs were screened out by WES, candidate genes were ranked in descending order according to their relative impact with microtia. Label-free proteomic analysis showed that proteins significantly different between the groups were related with oxidative stress and energy metabolism. By real-time PCR and immunohistochemistry, we further verified the candidate genes between other sporadic microtia and normal ear chondrocytes, which showed threonine aspartase, cadherin-13, aldolase B and adiponectin were significantly upregulated in mRNA levels but were significantly lower in protein levels. ROS detection and mitochondrial membrane potential (∆ Ψ m) detection proved that oxidative stress exists in microtia chondrocytes. Conclusions: Our results not only spot new candidate genes by WES and label-free proteomics, but also speculate for the first time that metabolism and oxidative stress may disturb cartilage development and this might become therapeutic targets and potential biomarkers with clinical usefulness in the future. [ABSTRACT FROM AUTHOR]

Mutations in the GNAL gene, encoding Gaolf, are causative for an adult-onset, isolated dystonia that may provide unique insights into the etiology of adultonset idiopathic dystonia. Gaolf is an alpha subunit of heterotrimeric G protein that replaces Gas in the striatum and has unique expression patterns outside of the striatum. Gaolf additionally has defined molecular functions in GPCR signaling. These defined molecular pathways and expression pathways point to defined circuit deficits underlying the causes of this adult-onset dystonia that may provide additional insights into broader idiopathic dystonia. Here, we will review the available evidence for normal Gaolf function, and how this is corrupted by GNAL mutations to cause dystonia. Thes include the molecular signaling and expression profiles of Gaolf and the other G proteins, β2±7, complexedwith it., Additionally, we will discuss the circuits that Gaolf influences, and how GNAL mutations may reorganize these circuits to cause dystonia. [ABSTRACT FROM AUTHOR]

Simple Summary: Simple Summary: Our research, made possible by recent advancements, has led to more accurate diagnoses of ancient pathologies, despite the rarity of well-preserved specimens, the predominance of bone remains, and the difficulty in distinguishing neoplastic from non-neoplastic lesions in fossils. This study compiles reports of tumours in fossilised animals, highlighting that neoplasms are present in various vertebrates and drawing comparisons to modern instances of similar diseases, thereby providing unique insights into the presence of tumours in ancient animals. Paleo-oncology studies neoplastic diseases in fossilised animals, including human remains. Recent advancements have enabled more accurate diagnoses of ancient pathologies despite the inherent challenges in identifying tumours in fossils—such as the rarity of well-preserved specimens, the predominance of bone remains, and the difficulty in distinguishing neoplastic from non-neoplastic lesions. This study compiles reports of tumours in fossilised animals, highlighting that neoplasms are present in a wide range of vertebrates and drawing comparisons to modern instances of similar diseases. The findings underscore the multifactorial aetiology of tumours, which involves genetic, environmental, and lifestyle factors, and suggest that tumours have been around for at least 350 million years. [ABSTRACT FROM AUTHOR]

Introduction: It has been increasingly recognised that the impact of Ataxia extends beyond physical and motor symptomology. However, it is less known whether self-reported non-motor and ataxia symptom severity varies across ataxias of differing aetiology, which would have important implications for providing more targeted treatment. Aim: This study aimed to investigate the impact of ataxia aetiology (hereditary, acquired or idiopathic) on self-reported depression, anxiety, fatigue, cognitive deficits, and ataxia symptom severity. Comparisons were also made between the ataxia sample as a whole and a neurologically healthy control group. Method: Responses were collected using a cross-sectional online survey to recruit a national UK sample of people with ataxia. Results: The study recruited 110 participants with ataxia (hereditary = 51, acquired = 16, idiopathic = 43) and 32 healthy controls. No significant differences were found across study variables for different causes of ataxia. However, participants with ataxia did report significantly higher levels of depression, anxiety, fatigue, cognitive deficits, and ataxia symptom severity compared to healthy controls. Conclusion: This study found that participants with ataxia self-reported increased non-motor symptoms compared to healthy controls, which was a generally homogenous experience across different causes of ataxia. There was also considerable comorbidity of symptoms which requires further exploration. This study highlights the need for early assessment and intervention to address these non-motor symptoms in ataxia populations. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTI) are common in under-five children, with significant consequences leading to bacteremia, dehydration, kidney scarring, and renal failure. The incidence of UTI varies with patients' demographics and geographic location. Limited studies have addressed UTI issues, particularly in children. We determined the proportion of UTI, bacterial aetiology, and antimicrobial susceptibility patterns and associated factors among under-five children at the district hospital between March and April 2023 Methods: We conducted a cross-sectional study using a convenient non-probability sampling technique to collect urine samples from participants with signs and symptoms of UTI. Written informed consent was obtained from parents or guardians. We collected Participants' information using a pretested structured questionnaire. Urine samples were processed at the Regional Referral Hospital. All analyses were conducted using STATA version 15.0. We determined the factors associated with UTI using a modified Poisson model multivariable analysis of the modified Poisson model. The results were presented as a prevalence ratio and 95% confidence interval. The level of significance was specified at 0.05. Result: The study recruited 368 under-five children; 194 (52.7%) were males, and the median age (interquartile range) was 24 (13–36) months. Of all, 28.8% (95% CI-24.3–33.6) had culture-confirmed UTI. One hundred and six pathogens were isolated, the majority being Escherichia coli (E. coli), 37 (34.9%), and Staphylococcus aureus (S. aureus), 26 (24.5%). The susceptibility of E. coli to cefepime, piperacillin-tazobactam, nitrofurantoin, and meropenem ranged from 81.1% to 97.3%. S. aureus was most susceptible to nitrofurantoin (96.2%) and ciprofloxacin (92.3%). Multidrug resistance was observed in 33.0% of isolates. The proportion of Methicillin-resistant S. aureus and extended-spectrum beta-lactamases was 23.1% and 25%, respectively. UTI was observed more in patients presenting with vomiting, dysuria, and abdominal pain, patients below 24 months of age, nappy users, and uncircumcised males. Conclusion: Our study found a relatively high proportion of UTI among under-five children associated with vomiting, dysuria, abdominal pain, nappy use, and uncircumcision in males. The pathogens were least susceptible to (trimethoprim-sulfamethoxazole, gentamycin, ampicillin, and penicillin) the commonly used antibiotic. We advocate a thorough clinical analysis to detect the predictors of UTI and a periodic review of empirical treatment of UTI based on the antibiotic susceptibility pattern. [ABSTRACT FROM AUTHOR]

Background: Rosacea is a prevalent chronic dermatological condition marked by facial inflammation and erythema, significantly compromising the quality of life for affected individuals. Current treatment methods for rosacea are not considered ideal because of the complex etiology of the disease. Mussel adhesive protein (MAP) is a glycoprotein derived from the foot gland of mussels. The protein exhibits anti‐inflammatory properties, relieves skin itching, and promotes wound healing. Aims: We aimed to explore the feasibility of using MAP administered via microneedle delivery for treating rosacea and the potential molecular mechanism involved. Materials and Methods: The therapeutic effect and mechanism of MAP microneedle delivery in an LL‐37‐induced rosacea‐like mouse model were observed using morphological and histological methods. Twenty‐seven patients with erythematotelangiectatic rosacea (ETR) underwent treatment once every 1 month, with three treatments constituting one treatment course. The therapeutic effect was evaluated by comparing the clinical images taken at baseline, after the first treatment course, and after the second treatment course. The red value, CEA, and GFSS score were also calculated. Results: In response to the microneedle delivery of MAP, innate immunity, inflammatory infiltration, and abnormal neurovascular regulation improved significantly in rosacea‐like mice. In the clinical experiments, the microneedle delivery of MAP significantly improved the symptoms of erythema, flushing, and telangiectasia in patients with ETR, and no obvious adverse reactions were observed. Conclusions: MAP delivered by microneedling is effective and safe for treating ETR. [ABSTRACT FROM AUTHOR]

This document is an editorial from the International Journal of Molecular Sciences titled "Strategies to Counteract Oxidative Stress and Inflammation in Chronic-Degenerative Diseases 2.0." It discusses the role of oxidative stress and inflammation in chronic degenerative diseases such as cancer, metabolic syndrome, type 2 diabetes, cardiovascular diseases, and neurodegenerative disorders. The editorial highlights the importance of identifying new tools to counteract these diseases and presents research articles and reviews that explore strategies to mitigate oxidative stress and inflammation through lifestyle modifications and therapeutic interventions. The document emphasizes the need for interdisciplinary collaboration and ongoing research to advance our understanding and management of these diseases. [Extracted from the article]

Neuroinfections rank among the top ten leading causes of child mortality globally, even in high-income countries. The crucial determinants for successful treatment lie in the timing and swiftness of diagnosis. Although viruses constitute the majority of infectious neuropathologies, diagnosing and treating viral neuroinfections remains challenging. Despite technological advancements, the etiology of the disease remains undetermined in over half of cases. The identification of the pathogen becomes more difficult when the infection is caused by atypical pathogens or multiple pathogens simultaneously. Furthermore, the modern surge in global passenger traffic has led to an increase in cases of infections caused by pathogens not endemic to local areas. This review aims to systematize and summarize information on neuroinvasive viral pathogens, encompassing their geographic distribution and transmission routes. Emphasis is placed on rare pathogens and cases involving atypical pathogens, aiming to offer a comprehensive and structured catalog of viral agents with neurovirulence potential. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC), a prevalent solid carcinoma of significant concern, is an aggressive and often fatal disease with increasing global incidence rates and poor therapeutic outcomes. The etiology and pathological progression of non-alcoholic steatohepatitis (NASH)-related HCC is multifactorial and multistage. However, no single animal model can accurately mimic the full NASH-related HCC pathological progression, posing considerable challenges to transition and mechanistic studies. Herein, a novel conditional inducible wild-type human HRAS overexpressed mouse model (HRAS-HCC) was established, demonstrating 100% morbidity and mortality within approximately one month under normal dietary and lifestyle conditions. Advanced symptoms of HCC such as ascites, thrombus, internal hemorrhage, jaundice, and lung metastasis were successfully replicated in mice. In-depth pathological features of NASH- related HCC were demonstrated by pathological staining, biochemical analyses, and typical marker gene detections. Combined murine anti-PD-1 and sorafenib treatment effectively prolonged mouse survival, further confirming the accuracy and reliability of the model. Based on protein-protein interaction (PPI) network and RNA sequencing analyses, we speculated that overexpression of HRAS may initiate the THBS1-COL4A3 axis to induce NASH with severe fibrosis, with subsequent progression to HCC. Collectively, our study successfully duplicated natural sequential progression in a single murine model over a very short period, providing an accurate and reliable preclinical tool for therapeutic evaluations targeting the NASH to HCC continuum. [ABSTRACT FROM AUTHOR]

Medically unexplained symptoms (MUS) remain recalcitrant to the medical profession, proving less suitable for homogenic treatment with respect to their aetiology, taxonomy and diagnosis. While the majority of existing medical research methods are designed for large scale population data and sufficiently homogenous groups, MUS are characterised by their heterogenic and complex nature. As a result, MUS seem to resist medical scrutiny in a way that other conditions do not. This paper approaches the problem of MUS from a philosophical point of view. The aim is to first consider the epistemological problem of MUS in a wider ontological and phenomenological context, particularly in relation to causation. Second, the paper links current medical practice to certain ontological assumptions. Finally, the outlines of an alternative ontology of causation are offered which place characteristic features of MUS, such as genuine complexity, context-sensitivity, holism and medical uniqueness at the centre of any causal set-up, and not only for MUS. This alternative ontology provides a framework in which to better understand complex medical conditions in relation to both their nature and their associated research activity. [ABSTRACT FROM AUTHOR]

Background: Stimulation of the spinal cord has been shown to have great potential for improving function after motor deficits caused by injury or pathological conditions. Using a wide range of animal models, many studies have shown that stimulation applied to the neural networks intrinsic to the spinal cord can result in a dramatic improvement of motor ability, even allowing an animal to step and stand after a complete spinal cord transection. Clinical use of this technology, however, has been slow to develop due to the invasive nature of the implantation procedures, the lack of versatility in conventional stimulation technology, and the difficulty of ascertaining specific sites of stimulation that would provide optimal amelioration of the motor deficits. Moreover, the development of tools available to control precise stimulation chronically via biocompatible electrodes has been limited. In this paper, we outline the development of this technology and its use in the spinal rat model, demonstrating the ability to identify and stimulate specific sites of the spinal cord to produce discrete motor behaviors in spinal rats using this array. Methods: We have designed a chronically implantable, rapidly switchable, high-density platinum based multi-electrode array that can be used to stimulate at 1-100 Hz and 1-10 V in both monopolar and bipolar configurations to examine the electrophysiological and behavioral effects of spinal cord epidural stimulation in complete spinal cord transected rats. Results: In this paper, we have demonstrated the effectiveness of using high-resolution stimulation parameters in the context of improving motor recovery after a spinal cord injury. We observed that rats whose hindlimbs were paralyzed can stand and step when specific sets of electrodes of the array are stimulated tonically (40 Hz). Distinct patterns of stepping and standing were produced by stimulation of different combinations of electrodes on the array located at specific spinal cord levels and by specific stimulation parameters, i.e., stimulation frequency and intensity, and cathode/anode orientation. The array also was used to assess functional connectivity between the cord dorsum to interneuronal circuits and specific motor pools via evoked potentials induced at 1 Hz stimulation in the absence of any anesthesia. Conclusions: Therefore the high density electrode array allows high spatial resolution and the ability to selectively activate different neural pathways within the lumbosacral region of the spinal cord to facilitate standing and stepping in adult spinal rats and provides the capability to evoke motor potentials and thus a means for assessing connectivity between sensory circuits and specific motor pools and muscles. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis (RAS; recurrent aphthous ulcers -- RAU; canker sores) is a chronic inflammatory, ulcerative condition of the oral mucosa. Its prevalence in the general population ranges between 5% and 20%, depending on the method and group studied. The etiopathogenesis of the disease is considered to be multifactorial, but remains still not fully understood. In patients with RAS, an enhanced immunologic response occurs to some trigger factors that may include: mechanical injury, stress or bacterial and viral antigens. Higher prevalence of aphthae in relatives may also indicate the genetic background of the condition. The inheritance of some specific gene polymorphisms, especially those encoding proinflammatory cytokines, which play a role in the formation of aphthous ulcer, may predispose family members to RAS. The purpose of this paper was to present the main clinical features of recurrent aphthous stomatitis, epidemiologic data and crucial etiopathogenetic factors with a special emphasis on genetic background of the condition. [ABSTRACT FROM AUTHOR]

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Background: An increasing use of point of care diagnostic tests that exclude malaria, coupled with a declining malaria burden in many endemic countries, is highlighting the lack of ability of many health systems to manage other causes of febrile disease. A lack of knowledge of distribution of these pathogens, and a lack of screening and point-of-care diagnostics to identify them, prevents effective management of these generally treatable contributors to disease burden. While prospective data collection is vital, an untapped body of knowledge already exists in the published health literature. Methods: Focusing on the Mekong region of Southeast Asia, published data from 1986 to 2011 was screened to for frequency of isolation of pathogens implicated in aetiology of non-malarial febrile illness. Eligibility criteria included English-language peer-reviewed studies recording major pathogens for which specific management is likely to be warranted. Of 1,252 identified papers, 146 met inclusion criteria and were analyzed and data mapped. Results: Data tended to be clustered around specific areas where research institutions operate, and where resources to conduct studies are greater. The most frequently reported pathogen was dengue virus (n = 70), followed by Orientia tsutsugamushi and Rickettsia species (scrub typhus/murine typhus/spotted fever group n = 58), Leptospira spp. (n = 35), Salmonella enterica serovar Typhi and Paratyphi (enteric fever n = 24), Burkholderia pseudomallei (melioidosis n = 14), and Japanese encephalitis virus (n = 18). Wide tracts with very little published data on aetiology of fever are apparent. Discussion and Conclusions: This mapping demonstrates a very heterogeneous distribution of information on the causes of fever in the Mekong countries. Further directed data collection to address gaps in the evidence-base, and expansion to a global database of pathogen distribution, is readily achievable, and would help define wider priorities for research and development to improve syndromic management of fever, prioritize diagnostic development, and guide empirical therapy. [ABSTRACT FROM AUTHOR]

The concept of developmental origins of health and disease has been defined as the process through which the environment encountered before birth, or in infancy, shapes the long-term control of tissue physiology and homeostasis. The evidence for programming derives from a large number of experimental and epidemiological observations. Several nutritional interventions during diverse phases of pregnancy and lactation in rodents are associated with fetal and neonatal programming for metabolic syndrome. In this paper, recent experimental models and human epidemiological studies providing evidence for the fetal programming associated with the development of metabolic syndrome and related diseases are revisited. [ABSTRACT FROM AUTHOR]

Arecanut (AN) usage is widespread in Asian countries, especially India and Taiwan. The incidence of oral cancer is increasing day by day, but there is no exponential increase with tobacco usage. Especially in the country like Taiwan where betel quid mostly do not contain tobacco, AN can be correlated with the increased incidence of cancer. There are different studies in the literature about AN and oral cancer but none of them have concluded with the definite pathway for carcinogenesis. The present paper includes reviews of the literature for AN and oral cancer and summarizes the possible mechanisms associated with AN-induced carcinogenesis; and we have also tried to propose pathway of carcinogenesis. [ABSTRACT FROM AUTHOR]

Both osteoporotic fractures and pleural effusions are frequently observed in medicine. However, rarely does one associate a hemorrhagic pleural effusion with a thoracic spinal fracture when the patient has not sustained massive trauma. In this paper, we discuss two cases where seemingly insignificant low-energy trauma precipitated massive haemothoraces in elderly patients with underlying osteoporosis, ultimately resulting in their immediate causes of death. This paper serves to remind health care professionals of the importance of using caution when moving elderly patients as well as to consider thoracic spinal fracture as a potential explanation for a hemorrhagic pleural effusion of undetermined etiology. [ABSTRACT FROM AUTHOR]

In 1990, an association between thyroid antibody positivity and spontaneous miscarriage was first reported. A generation has passed since the initial observation. Over that time a robust literature has developed which has confirmed the initial finding and expanded upon it. The present paper reviews the literature that has been generated over the last twenty years on the following topics: (1) thyroid antibodies and spontaneous miscarriage, (2) thyroid antibodies and recurrent abortion, (3) etiology of pregnancy loss in thyroid antibody positive women, and (4) discussion of future research directions. [ABSTRACT FROM AUTHOR]

This paper discusses the range of recurrent oral ulceration which affects the oral mucosa. Types of ulceration covered in this paper include traumatic, infective, aphthous, ulceration related to the oral dermatoses, drug-induced, ulceration as a manifestation of systemic disease and ulceration indicating malignancy. Aspects of the aetiology, diagnosis and management of common oral recurrent ulcerative conditions are reviewed from a clinical perspective as an aid to practising dentists. [ABSTRACT FROM AUTHOR]

Background: People who suffer from mental illness, the professionals who treat them, and indeed the actual concept of mental illness are all stigmatised in public perception and often receive very negative publicity. This paper looks at Iraq, which has a population of 30 million who are mainly Moslem. Mental health services and professionals have historically been sparse in Iraq with 1 psychiatrist per 300,000 before 2003 falling to 1 per million until recently and 1 primary care centre (40 Healthcare Workers including 4 General Practitioners) to 35,000 population, compared with 1 GP per 1700 population in the UK. Methods: We aimed to assess public attitudes and perceptions to mental illness. Participants were asked to complete a questionnaire (additional file 1), which was designed specifically for Iraqi contexts and was made available in 2 languages. The survey was carried out in 500 participants' homes across 2 districts of Baghdad. Results: The response rate of the survey was 86.4%. The paper shows respondents views on the aetiology of mental illness, perceptions of people with mental illness and attitudes towards care and treatment of people with mental illness. Conclusions: This survey of public attitudes towards mental illness in Iraq has shown that community opinion about the aetiology of mental illness is broadly compatible with scientific evidence, but understanding of the nature of mental illness, its implications for social participation and management remains negative in general. [ABSTRACT FROM AUTHOR]

Vitamin D is unique among the vitamins in that man can synthesise it via the action of UV radiation upon the skin. This combined with its ability to act on specific target tissues via vitamin D receptors (VDR) make its classification as a steroid hormone more appropriate. While vitamin D deficiency is a recognised problem in some northern latitude countries, recent studies have shown that even in sunny countries, such as Australia, vitamin D deficiency may be more prevalent than first thought. Vitamin D is most well known for its role in bone health; however, the discovery of VDR on a wide variety of tissue types has also opened up roles for vitamin D far beyond traditional bone health. These include possible associations with autoimmune diseases such as multiple sclerosis and inflammatory bowel diseases, cancer, CVD and muscle strength. First, this paper presents an overview of the two sources of vitamin D: exposure to UVB radiation and food sources of vitamin D, with particular focus on both Australian and international studies on dietary vitamin D intake and national fortification strategies. Second, the paper reviews recent epidemiological and experimental evidence linking vitamin D and its role in health and disease for the major conditions linked to suboptimal vitamin D, while identifying significant gaps in the research and possible future directions for research. [ABSTRACT FROM AUTHOR]

This paper investigates the response of the land surface and the lowest section of the atmospheric surface layer to rainfall events and through the subsequent drying out period. The impacts of these sequences of rainfall and drying events in controlling near-surface temperatures are put into the context of malaria transmission modeling using temperature controls on the survivability of mosquitoes that are developing the malaria parasite. Observations using measurements from a dwelling hut, constructed to a local design at Wankama near Niamey, Niger, show that as the atmosphere gets moister and colder following rainfall, there is a potentially higher risk of malaria transmission during the rainy days. As the atmosphere gets warmer and drier during the drying period, there is a potentially decreasing rate of malaria transmission as the increasing temperature reduces the survivability of the mosquitoes. A numerical weather prediction model comparison shows that the high-resolution limited-area model outperforms the global-scale model and shows good agreement with the observations. Statistical analysis from the model results confirms that the findings are not restricted to a single location or single time of the day. It was also found that air temperatures over forest areas do not change as much during the study period, since the longer memory of the soil moisture means there is relatively little influence from single rainfall events. [ABSTRACT FROM AUTHOR]

Qualitative theories of illness experience are about the individual interpretations of the psychosocial and cultural aspects of living with illness. Thus, they contribute to a better understanding of health and health care provision. In this paper, we examine how a grounded theory (GT) of heart disease experience can inform secondary prevention. In-depth interviews of individual experience of heart disease were conducted with 26 patients, using GT iterative data collection and analysis framework. A GT was compiled from data and examined within a sociocultural framework to ascertain how experience influenced health behaviour. Despite individual contextual variations, the theory of 'keeping it going' describes the study sample's common attitude to living with heart disease. The theory was adequate in explaining secondary cardiac behaviour, because it identified the aspects of patients' beliefs and attitudes which are key to effective secondary prevention. The assessment of the impact of illness experience on health behaviour within a sociocultural framework helped to articulate the strong influence of social and contextual factors. The study offers an appropriate explanatory framework for encouraging health behaviour change. It emphasizes the importance of interventions being relevant to individual perceptions and interpretations. It provides a framework for designing and evaluating cardiac interventions and the theoretical principles which underpin them. [ABSTRACT FROM AUTHOR]

The article presents a study which examines the epidemiological link between shift work and the risk of ischemic heart disease. It notes that 14 studies on shift work and ischemic heart disease were reviewed, in which six were based on incidence data, seven on mortality data, and one used both types. It shows that the two papers reported relative risks around 2.0 while the 12 papers demonstrate relative risks ranging from 0.6-1.4, but evidences are limited for a causal relation between the two.

The genes PTPN22 and HLA-DRB1 have been found by a number of studies to confer an increased risk for rheumatoid arthritis (RA), which indicates that both genes play an important role in RA etiology. It is believed that they not only have strong association with RA individually, but also interact with other related genes that have not been found to have predisposing RA mutations. In this paper, we conduct genome-wide searches for RA-associated gene-gene interactions that involve PTPN22 or HLA-DRB1 using the Genetic Analysis Workshop 16 Problem 1 data from the North American Rheumatoid Arthritis Consortium. MGC13017, HSPCAL3, MIA, PTPNS1L, and IGLVI-70, which showed association with RA in previous studies, have been confirmed in our analysis. [ABSTRACT FROM AUTHOR]

Background: Bayesian networks are powerful instruments to learn genetic models from association studies data. They are able to derive the existing correlation between genetic markers and phenotypic traits and, at the same time, to find the relationships between the markers themselves. However, learning Bayesian networks is often non-trivial due to the high number of variables to be taken into account in the model with respect to the instances of the dataset. Therefore, it becomes very interesting to use an abstraction of the variable space that suitably reduces its dimensionality without losing information. In this paper we present a new strategy to achieve this goal by mapping the SNPs related to the same gene to one meta-variable. In order to assign states to the meta-variables we employ an approach based on classification trees. Results: We applied our approach to data coming from a genome-wide scan on 288 individuals affected by arterial hypertension and 271 nonagenarians without history of hypertension. After pre-processing, we focused on a subset of 24 SNPs. We compared the performance of the proposed approach with the Bayesian network learned with SNPs as variables and with the network learned with haplotypes as meta-variables. The results were obtained by running a hold-out experiment five times. The mean accuracy of the new method was 64.28%, while the mean accuracy of the SNPs network was 58.99% and the mean accuracy of the haplotype network was 54.57%. Conclusion: The new approach presented in this paper is able to derive a gene-based predictive model based on SNPs data. Such model is more parsimonious than the one based on single SNPs, while preserving the capability of highlighting predictive SNPs configurations. The prediction performance of this approach was consistently superior to the SNP-based and the haplotype-based one in all the test sets of the evaluation procedure. The method can be then considered as an alternative way to analyze the data coming from association studies. [ABSTRACT FROM AUTHOR]

The development of modern epidemiology, particularly cancer epidemiology, is often seen as a post-World War II phenomenon. However, the First National Cancer Survey, conducted from 1937 to 1939 as part of the newly formed National Cancer Institute's initial activities, provided the first data on the occurrence of cancer in the United States. This project was directed by a young sociologist, Harold Fred Dom. Through Dom, many of the methodological innovations in sociology, such as the use of surveys and observational study designs, were incorporated into modern epidemiology. I examine Dorn's training and early career in the content of the First National Cancer Survey as a means of investigating the beginnings of modem epidemiology. (Am J Public Health. 2008;98:2150-2158. doi:10.2105/AJPH.2007.1l7440) [ABSTRACT FROM AUTHOR]

Many predictions of the economic and social costs of a modern-day pandemic are based on the effects of the influenza pandemic of 1918. Despite killing 675,000 people in the United States and 40 million worldwide, the influenza of 1918 has been nearly forgotten. The purpose of this paper is to provide an overview of the influenza pandemic of 1918 in the United States, its economic effects, and its implications for a modern-day pandemic. The paper provides a brief historical background as well as detailed influenza mortality statistics for cities and states, including those in the Eighth Federal Reserve District, that account for differences in race, income, and place of residence. Information is obtained from two sources: (i) newspaper articles published during the pandemic and (ii) a survey of economic research on the subject. (JEL I1, N0, R0) [ABSTRACT FROM AUTHOR]

Objective: This paper describes chemical injuries, which presented to us and were managed at a burn unit in Nigeria. The purpose of this paper is to highlight the etiologies of these injuries, the extent of the injuries as well as to suggest possible ways to prevent chemical injuries in our environment. Materials and Methods: We carried out a retrospective review of chemical burns treated at our center. Our sources of information were the burn unit admission registers, case notes of the patients and operation registers. The results were collated and then analyzed. Results: Twenty eight patients presented with chemical burn injuries during the study period between January 2000 and December 2003, constituting 5.7% of all patients with burns treated within that period. Seventeen (60.7%) of the patients were males while 11 (29.3%) were females with a mean age of 20.6 years. The injuries were sustained from assault in 21 (75%), armed robbery attacks in five (17.8%) and suicide attempts in two (7.1%). The agents were usually unknown. Late presentation was observed in all the patients. Raw eggs, palm oil, gentian violet and engine oil were the substances applied immediately after the injuries. Complications observed included septicemia, respiratory distress, blindness, renal failure, mentosternal contractures, ectropion, axillary contractures, hypertrophic scars, keloids and skin depigmentation. Conclusion: Chemical burn injuries are mainly due to assaults in Nigeria and are usually extensive and presented late. Education of the people and penalty for any offender will reduce the current spate of such injuries. [ABSTRACT FROM AUTHOR]

BACKGROUND: Evidence is mounting that environmental exposures contribute to causation of disease in children. Yet few pediatricians are trained to diagnose, treat, or prevent disease of environmental origin. OBJECTIVES: To develop a cadre of future leaders in pediatric environmental health (PEH), the Ambulatory Pediatric Association (APA) launched a new 3-year fellowship in 2001—the world's first formal training program in PEH. Sites were established at Boston Children's Hospital, Mount Sinai School of Medicine, George Washington University, University of Cincinnati, and University of Washington. Fellows are trained in epidemiology, biostatistics, toxicology, risk assessment, and preventive medicine. They gain clinical experience in environmental pediatrics and mentored training in clinical research, policy development, and evidence-based advocacy. Thirteen fellows have graduated. Two sites have secured follow-on federal funding to enable them to continue PEH training. DISCUSSION: To assess objectively the program's success in preparing fellows for leadership careers in PEH, we conducted a mailed survey in 2006 with follow-up in 2007. CONCLUSIONS: Fifteen (88%) of 17 fellows and graduates participated; program directors provided information on the remaining two. Nine graduates are pursuing full-time academic careers, and two have leadership positions in governmental and environmental organizations. Ten have published one or more first-authored papers. Seven graduates are principal investigators on federal or foundation grants. The strongest predictors of academic success are remaining affiliated with the fellowship training site and devoting < 20% of fellowship time to clinical practice. CONCLUSION: The APA fellowship program is proving successful in preparing pediatricians for leadership careers in PEH. [ABSTRACT FROM AUTHOR]

In 1906, James McKeen Cattell, editor of Science, published a directory of men of science. American Men of Science was a collection of biographical sketches of thousands of men of science in the USA and was published periodically. It launched, and was used in, the very first systematic quantitative studies on science. Cattell used two concepts for his statistics: productivity, defined as the number of men of science a nation produces, and performance or merit, defined as scientific contributions to research as judged by peers. These are the two dimensions that still define measurement of scientific productivity today: quantity and quality. This paper analyzes the emergence of statistics on science and the very first uses to which they were put. It argues that the measurement of science emerged out of interest in great men, heredity and eugenics, and the contribution of eminent men to civilization. Among these eminent men were men of science, the population of whom was thought to be in decline and insufficiently appreciated and supported. Statistics on men of science thus came to be collected to document the case, and to contribute to the advancement of science and the scientific profession. [ABSTRACT FROM AUTHOR]

Whilst the prevention of childhood obesity is the only viable, enduring, cost-effective solution to the obesity epidemic, effective methods for it remain elusive. Furthermore, strategies to influence obesogenic environments remain relatively unexplored. In order to be able to develop powerful population-level interventions and public health policies to prevent childhood obesity, it is important to understand its aetiology and those environments that are most amenable to measurable change. First, the present paper considers why we should be concerned about obesity in children, from both the perspective of the increased health risk to the individual and the high economic cost of treatment of obesity and related diseases, highlighting why the prevention of childhood obesity is important. Next, the determinants of health behaviour and the obesogenic environment are explored, which helps us to understand why the aetiology is so complex and that potential causal factors should not be considered in isolation, as the interaction between these factors is also important. The paper then considers the multi-factorial aetiology of childhood obesity and the rationale for the increasing trends in obesity that are evident, in order to understand what is changing in society and our children's behaviour that is triggering the positive energy balance leading to obesity. The review emphasises the need for multi-level approaches if we truly want to prevent childhood obesity. It also serves to highlight that there is a need to extend the current research base in order to build a well-founded framework to form the basis of a strategy for the prevention of childhood obesity. [ABSTRACT FROM AUTHOR]

A recent rise in the reporting of diseases in marine organisms has raised concerns that ocean health is deteriorating. The goal of this study was to determine whether or not there has been a recent deterioration in marine mammal health by investigating the trends in disease reports over the past 40 years (categorized by the method of study, the species affected, and the etiology of the disease) and by exploring the changes in frequency of mass mortality events among marine mammals reported in the United States since 1978. The number of papers on marine mammal disease published each year has increased since 1966, although the annual publication rate appears to have stabilized since ∼1992. Those published in the 1960s and 1970s were largely about helminth and bacterial disease, those investigating viruses emerged in the late 1970s and increased in the 1980s and 1990s, whereas protozoal diseases and harmful algal toxins were largely not reported until the 1990s. The annual number of mass mortality events in the U.S. approximately doubled between 1980 and 1990 but since 2000 has been between seven and eight events per year. Causes of mass mortality events have included biotoxins, viruses, bacteria, parasites, human interactions, oil spills, and changes in oceanographic conditions. Events due to biotoxins appear to be increasing, but the change in the frequency of mass mortality events from other causes over the past 40 years cannot be determined from the available published literature due to changes in marine mammal abundance, inconsistencies in effort and extent of resources for pathological investigation, and advances in technology that have allowed improved detection of pathogens and toxins in more recent years. To ensure future information on the true incidence of marine diseases and their underlying causes is more reliable, specific and directed marine health monitoring programs, well-equipped stranding networks, and dedicated diagnostic laboratories are needed. [ABSTRACT FROM AUTHOR]

Background: In the last 15 y there has been a tremendous increase in the number of studies on pediatric obesity looking at epidemiology, health-related risks, etiology, methodology and treatment. During the early 1990s, the European Childhood Obesity Group (ECOG) was born as a group of scientists' expert in the field of pediatric obesity. ECOG this year celebrates the approach to early maturity with an excited and omni-comprehensive program developing through eight different tracks.Methods: Comments on different 'key' papers in each of the eight tracks.Results: The eight tracks were (1) Nutrition requirements and food habits, (2) physical activity, (3) prevention and political actions/strategies, (4) diabetes, (5) metabolism, (6) psychology, (7) pathology, and (8) treatment with emphasis on drugs.Conclusion: Looking at the overall picture of the ECOG workshop we could conclude that despite the fact that childhood obesity is a crisis facing worldwide youth, it is necessary that action to control it must be taken now. All the six relevant levels (ie, family, schools, health professionals, government, industry and media) could be involved in prevention of child and adolescent obesity. [ABSTRACT FROM AUTHOR]

This paper provides a critique of the common practice in the health-policy literature of focusing on hypothetical outcome removal at the expense of intervention analysis. The paper begins with an introduction to measures of causal effects within the potential-outcomes framework, focusing on underlying conceptual models, definitions and drawbacks of special relevance to policy formulation based on epidemiologic data. It is argued that, for policy purposes, one should analyze intervention effects within a multivariate-outcome framework to capture the impact of major sources of morbidity and mortality. This framework can clarify what is captured and missed by summary measures of population health, and shows that the concept of summary measure can and should be extended to multidimensional indices. [ABSTRACT FROM AUTHOR]

Copyright of RGO: Revista Gaúcha de Odontologia is the property of RGO: Revista Gaucha de Odontologia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The precautionary principle brings a special challenge to the practice of evidence-based public health decision-making, suggesting changes in the interpretative methods of public health used to identify causes of disease. In this paper, precautionary changes to these methods are examined: including discounting contrary evidence, reducing the number of causal criteria, weakening the rules of evidence assigned to the criteria, and altering thresholds for statistical significance. All such changes reflect the precautionary goal of earlier primary preventive intervention, i.e. acting on insufficient evidence, the least amount, or minimum level, of evidence for causation. Evaluating the impact of these changes will be difficult without a careful study of how well the current methods of causal inference work, their theoretical foundations, and the ethical implications of their applications. That research program will be most productive if it is jointly developed by public health professionals trained in the ethics and philosophy and by bioethicists and philosophers trained in the theories, methods, and practice of public health. [ABSTRACT FROM AUTHOR]

Osteoarthritis is a chronic degenerative disorder characterised by cartilage loss. It is extremely prevalent in society and is a major cause of disability. It is important to treat osteoarthritis effectively using a multidisciplinary approach tailored to the patient's needs. This paper reviews current thinking on the aetiology, pathogenesis, investigations, and management of osteoarthritis. The paper also discusses the challenges for developing good quality outcome measures for use in large scale multicentre clinical trials for new osteoarthritis treatments, especially disease modifying osteoarthritis drugs. [ABSTRACT FROM AUTHOR]

Multiple time-dynamic and interrelated risk factors are usually involved in the complex etiology, of disorders. This paper presents a strategy to explore and display visually the relative importance of different association pathways for the onset of disorder over time. The approach is based on graphical chain models, a tool that is powerful but still underutilized in most fields. Usually, the results of these models are displayed using directed acyclic graphs (DAGs). These draw an edge between a pair of variables whenever the assumption of conditional independence given variables on an earlier or equal temporal footing is violated to a statistically significant extent. In the present paper, the graphs are modified in that confidence intervals for the strengths of associations (statistical main effects) are visualized. These new graphs are called association chain graphs (ACGs). Statistical interactions cause 'edges' between the respective variables within the DAG framework (because the assumption of conditional independence is violated). In contrast they are represented as separate graphs within the subsample where the different association chains ,nay work within the ACG framework. With this new type of graph, more specific information can be displayed whenever the data are essentially described only with statistical main- and two-way interaction effects. [ABSTRACT FROM AUTHOR]

Definitions of epidemiological concepts regarding disease monitoring and surveillance can be found in textbooks on veterinary epidemiology. This paper gives a review of how the concepts: monitoring, surveillance, and disease control strategies are defined. Monitoring and surveillance systems (MO&SS) involve measurements of disease occurrence, and the design of the monitoring determines which types of disease occurrence measures can be applied. However, the knowledge of the performance of diagnostic tests (sensitivity and specificity) is essential to estimate the true occurrence of the disease. The terms, disease control programme (DCP) or disease eradication programme (DEP), are defined, and the steps of DCP/DEP are described to illustrate that they are a process rather than a static MO&SS. [ABSTRACT FROM AUTHOR]

Purpose: This review aimed to highlight the aetiology and risk factors of food impaction along with the treatment in each case. Materials and Methods: A search was conducted in PubMed from 1947 to March 28, 2023. The search terms utilised included (food impaction) OR (interdental impaction). No filter was applied. Articles related to the classification, aetiology, treatment, and associated factors of food impaction in dentistry and published in English or with an abstract in English were selected. Results: A total of 72 articles were included in the review, which revealed the variety and complexity of aetiological factors and treatment of food impaction in dentistry, as well as the heterogeneity of previous studies. Based on the aetiology, different treatment plans and management should be considered. Conclusion: This review indicated the need to identify the pathology of food impaction before treatment. Considering the causal factors of food impaction -- including proximal contact loss, occlusal disharmony, morphological deformity, positional abnormality, and interdental papillae loss -- different management approaches such as restoration, occlusal adjustment, orthodontic, nonsurgical or surgical treatment could be applied. Further clinical and experimental research is warranted to address the prevention and treatment of food impaction in dentistry. [ABSTRACT FROM AUTHOR]

The seasonal variability of certain non-allergic respiratory diseases is not clearly understood. Analysis of the breath condensate, the liquid that can be collected by breathing into a cold tube, has been proposed to bring closer to the understanding of airway pathologies. It has been assumed, that (1) airway lining fluid was a stable body liquid and (2) the breath condensate samples were representative of the airway lining fluid. Research was focussed on the identification of biomarkers indicative of respiratory pathologies. Despite 30 years of extended investigations breath condensate analysis has not gained any clinical implementation so far. The pH of the condensate is the characteristic that can be determined with the highest reproducibility. The present paper shows, that contrary to the initial assumptions, breath condensate is not a representative of the airway lining fluid, and the airway lining fluid is not a stable body liquid. Condensate pH shows baseline variability and it is influenced by drinking and by the ambient temperature. The changes in condensate pH are linked to changes in airway lining fluid pH. The variability of airway lining fluid pH may explain seasonal incidence of certain non-allergic respiratory diseases such as the catching of a common cold and the increased incidence of COPD exacerbations and exercise-induced bronchoconstriction in cold periods. [ABSTRACT FROM AUTHOR]

Diagnosis of lower limb pain in an athlete can be a challenging task due to the variety of potential etiologies and ambiguity of presenting symptoms. Five of the most commonly encountered causes of limb pain in athletes are chronic exertional compartment syndrome (CECS), medial tibial stress syndrome (MTSS), tibial stress fractures, soleal sling syndrome, and popliteal artery entrapment syndrome (PAES). Of these, the least frequent but potentially most serious of the pathologies is PAES. With an incidence of less than 1% seen in living subject studies, the condition is rare. However, a missed diagnosis will likely lead to progression of the disease and potential for unnecessary invasive procedures (McAree et al. 2008). In this paper, we present a young athlete misdiagnosed and treated for chronic exertional compartment syndrome. In both descriptive and a quick-reference table format, we review current literature and discuss how best to distinguish functional PAES from other causes of activity-related leg pain. [ABSTRACT FROM AUTHOR]

Background and Aims: Preventive strategies of congenital anomalies are basically relying on the systematic ongoing collection and analysis of data and timely dissemination of information. The aim of this paper is to briefly report a critical review of a surveillance system of congenital anomalies in a developing country, by describing the challenges and experience of the registry since it began.Methods: Tabriz Registry of Congenital Anomalies (TRoCA) was mainly set up based on the guidelines provided by the International Clearinghouse for Birth Defects Surveillance and Research (ICBDSR) for data collection, coding, process, analysis, use, and evaluation of the system.Findings: TRoCA has successfully achieved its main objective as a pilot model for setting up a nationwide registry of congenital anomalies in the country. The programme has too succeeded in relation to its regional objectives: epidemiological rates and data have been produced consistently for etiological investigations, methodological studies, service provision, and preventive measures for selected anomalies.Conclusions: Our successful experience, as a small registry in a developing country, might be of interest and useful to practitioners, policymakers of birth defects control programmes, and mainly those willing to set up a monitoring system of congenital anomalies in similar areas. [ABSTRACT FROM AUTHOR]

Copyright of Revista Facultad de Medicina de la Universidad Nacional de Colombia is the property of Universidad Nacional de Colombia and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Introduction: One of the common syndromes that affect humanity is neuropathic pain (NP), yet poorly understood with no efficient treatment till now. Consequently, it is extremely crucial to seek further evidence for accurate diagnosis and optimum treatment. The aim of this work is to summarize the findings related to neuropathic pain in terms of etiology, types, diagnosis, current and future management prospective, and identify the gaps in neuropathic pain therapy. Methods: A literature investigation was carried out by analyzing classical peer reviewed papers and textbooks, taking into consideration worldwide well established scientific databases mainly PUBMED and SCOPUS to retrieve accessible published literature. The selection of phytotherapies was based upon their potentials in relieving NP in pre-clinical or clinical models. Results: One of the most critical points in this research is that recommendations of the future plans should be focused on the engagement of phytotherapy in the treatment regimen aiming at improving patients' quality of life and reaching optimum effi- cacy and minimum toxicity. Phytotherapies offer relatively low-risk options to NP patients and have an increasing evidence to be the future of neuropathic pain management. Patients suffering from neuropathy are depending increasingly on phytotherapies; however, they need more clinical trials in order to fully understand their mechanism of actions. Conclusion: Health-care specialists should be regularly informed about neuropathic pain current therapies and promising future phytotherapies, bearing in mind the risk/benefit profile of the utilization of these therapies in the amelioration of NP. [ABSTRACT FROM AUTHOR]

Electroencephalography signals are typically used for analyzing epileptic seizures. These signals are highly nonlinear and nonstationary, and some specific patterns exist for certain disease types that are hard to develop an automatic epileptic seizure detection system. This paper discussed statistical mechanics of complex networks, which inherit the characteristic properties of electroencephalography signals, for feature extraction via a horizontal visibility algorithm in order to reduce processing time and complexity. The algorithm transforms a time series signal into a complex network, which some features are abbreviated. The statistical mechanics are calculated to capture distinctions pertaining to certain diseases to form a feature vector. The feature vector is classified by multiclass classification via a k-nearest neighbor classifier, a multilayer perceptron neural network, and a support vector machine with a 10-fold cross-validation criterion. In performance evaluation of proposed method with healthy, seizure-free interval, and seizure signals, firstly, input data length is regarded among some practical signal samples by optimizing between accuracy-processing time, and the proposed method yields outstanding performance on the average classification accuracy for 3-class problems mainly for detection of seizure-free interval and seizure signals and acceptable results for 2-class and 5-class problems comparing with conventional methods. The proposed method is another tool that can be used for classifying signal patterns, as an alternative to time/frequency analyses. [ABSTRACT FROM AUTHOR]

Background: A major challenge of bioinformatics in the era of precision medicine is to identify the molecular biomarkers for complex diseases. It is a general expectation that these biomarkers or signatures have not only strong discrimination ability, but also readable interpretations in a biological sense. Generally, the conventional expressionbased or network-based methods mainly capture differential genes or differential networks as biomarkers, however, such biomarkers only focus on phenotypic discrimination and usually have less biological or functional interpretation. Meanwhile, the conventional function-based methods could consider the biomarkers corresponding to certain biological functions or pathways, but ignore the differential information of genes, i.e., disregard the active degree of particular genes involved in particular functions, thereby resulting in less discriminative ability on phenotypes. Hence, it is strongly demanded to develop elaborate computational methods to directly identify functional network biomarkers with both discriminative power on disease states and readable interpretation on biological functions. Results: In this paper, we present a new computational framework based on an integer programming model, named as Comparative Network Stratification (CNS), to extract functional or interpretable network biomarkers, which are of strongly discriminative power on disease states and also readable interpretation on biological functions. In addition, CNS can not only recognize the pathogen biological functions disregarded by traditional Expression-based/Networkbased methods, but also uncover the active network-structures underlying such dysregulated functions underestimated by traditional Function-based methods. To validate the effectiveness, we have compared CNS with five state-of-the-art methods, i.e. GSVA, Pathifier, stSVM, frSVM and AEP on four datasets of different complex diseases. The results show that CNS can enhance the discriminative power of network biomarkers, and further provide biologically interpretable information or disease pathogenic mechanism of these biomarkers. A case study on type 1 diabetes (T1D) demonstrates that CNS can identify many dysfunctional genes and networks previously disregarded by conventional approaches Conclusion: Therefore, CNS is actually a powerful bioinformatics tool, which can identify functional or interpretable network biomarkers with both discriminative power on disease states and readable interpretation on biological functions. CNS was implemented as a Matlab package, which is available at http://www.sysbio.ac.cn/cb/chenlab/ images/CNSpackage_0.1.rar. [ABSTRACT FROM AUTHOR]

Background: The opportunity to assess short term impact of air pollution relies on the causal interpretation of the exposure-response association. However, up to now few studies explicitly faced this issue within a causal inference framework. In this paper, we reformulated the problem of assessing the short term impact of air pollution on health using the potential outcome approach to causal inference. We considered the impact of high daily levels of particulate matter ≤10 μm in diameter (PM10) on mortality within two days from the exposure in the metropolitan area of Milan (Italy), during the period 2003-2006. Our research focus was the causal impact of a hypothetical intervention setting daily air pollution levels under a pre-fixed threshold.Methods: We applied a matching procedure based on propensity score to estimate the total number of attributable deaths (AD) during the study period. After defining the number of attributable deaths in terms of difference between potential outcomes, we used the estimated propensity score to match each high exposure day, namely each day with a level of exposure higher than 40 μg/m3, with a day with similar background characteristics but a level of exposure lower than 40 μg/m3. Then, we estimated the impact by comparing mortality between matched days.Results: During the study period daily exposures larger than 40 μg/m3 were responsible for 1079 deaths (90% CI: 116; 2042). The impact was more evident among the elderly than in the younger age classes. Exposures ≥ 40 μg/m3 were responsible, among the elderly, for 1102 deaths (90% CI: 388, 1816), of which 797 from cardiovascular causes and 243 from respiratory causes. Clear evidence of an impact on respiratory mortality was found also in the age class 65-74, with 87 AD (90% CI: 11, 163).Conclusions: The propensity score matching turned out to be an appealing method to assess historical impacts in this field, which guarantees that the estimated total number of AD can be derived directly as sum of either age-specific or cause-specific AD, unlike the standard model-based procedure. For this reason, it is a promising approach to perform surveillance focusing on very specific causes of death or diseases, or on susceptible subpopulations. Finally, the propensity score matching is free from issues concerning the exposure-confounders-mortality modeling and does not involve extrapolation. On the one hand this enhances the internal validity of our results; on the other, it makes the approach scarcely appropriate for estimating future impacts. [ABSTRACT FROM AUTHOR]