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Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD and disability grade in this population. Study Design: We retrospectively reviewed the clinical data of all patients (aged 3–18 years old) admitted during a three-month observation in our neurorehabilitation department. Data collected were as follows: demographic parameters; disability status (Wee-FIM Scale, Gross Motor Function Classification System (GMFCS) and the Communication Function Classification System); and gastrointestinal and urological symptoms (diaries, Bristol scale, Pad Test and International Consultation on Incontinence Modular Questionnaire). Results: Sixty patients were enrolled (31 females, 29 males): 30 CP, 17 ABI, 3 SCI, and 10 others with neurological diseases. All presented urinary incontinence without gender differences. CP and ABI had major incidences of bowel dysfunction (50% and 64.7%, respectively) and SCI of urinary tract infections (66.6%) and enuresis (100%). A major incidence of symptoms was recorded in patients with higher GMFCS levels (level 3-4-5). Conclusions: NBBD has a high frequency in children with CP and ABI, as in SCI. More attention is needed from pediatricians and pediatric urologists for this clinical entity. Further studies are needed to better understand clinical relevance and, therefore, to establish specific management.

Abstract The Italian‐native Mediterranean brown trout (Salmo ghigii) is a seriously threatened freshwater fish, especially by anthropogenic hybridisation with the domestic strains of Atlantic origin that have been repeatedly released into the wild for angling. A PCR‐restriction fragment length polymorphism (RFLP) assay of the diagnostic lactate dehydrogenase chain‐1 (LDH‐C1) gene sequences has been routinely applied to distinguish exotic from native brown trout lineages and detect Atlantic introgression signals in the Mediterranean wild populations. Here, we used dermal swab DNA obtained from 28 wild trout to improve laboratory procedures to genetically characterise trout samples at the LDH‐C1gene through (1) a capillary electrophoresis analysis of the RFLP fragments and (2) the optimisation of a diagnostic single nucleotide polymorphism analysable through mini‐sequencing approaches. The developed methods were fully consistent with those obtained through the traditional approach, but their analytical process is almost entirely automated and digitalised, thus improving result readability and accuracy in the detection of alien introgressed traces in wild Mediterranean brown trout populations.

Abstract Background During pregnancy, the increase in maternal insulin resistance is compensated by hyperplasia and increased function of maternal pancreatic beta cells; the failure of this compensatory mechanism is associated with gestational diabetes mellitus (GDM). Serotonin participates in beta cell adaptation, acting downstream of the prolactin pathway; the blocking of serotonin receptor B (HTR2B) signaling in pregnant mice impaired beta cell expansion and caused glucose intolerance. Thus, given the importance of the serotoninergic system for the adaptation of beta cells to the increased insulin demand during pregnancy, we hypothesized that genetic variants (single nucleotide polymorphisms [SNPs]) in the gene encoding HTR2B could influence the risk of developing GDM. Methods This was a case–control study. Five SNPs (rs4973377, rs765458, rs10187149, rs10194776, and s17619600) in HTR2B were genotyped by real-time polymerase chain reaction in 453 women with GDM and in 443 pregnant women without GDM. Results Only the minor allele C of SNP rs17619600 conferred an increased risk for GDM in the codominant model (odds ratio [OR] 2.15; 95% confidence interval [CI] 1.53–3.09; P

Abstract Background Gestational diabetes mellitus (GDM) is one of the most common complications affecting pregnant women. While most women will achieve adequate glycemic levels with diet and exercise, some will require pharmacological treatment to reach and maintain glucose levels between the desired thresholds. Identifying these patients early in pregnancy could help direct resources and interventions. Methods This retrospective cohort of women with GDM diagnosed with an abnormal 75g-OGTT presents data from 869 patients (724 in the diet group and 145 in the insulin group). Univariate logistic regression was used to compare the groups, and multivariable logistic regression was used to identify independent factors associated with the need for insulin. A log-linear function was used to estimate the probability of requiring pharmacological treatment. Results Women in the insulin group had higher pre-pregnancy BMI index (29.8 vs 27.8 kg/m2, odds ratio [OR] 1.06, 95% confidence interval [CI] 1.03–1.09), more frequent history of previous GDM (19.4% vs. 7.8%, OR 2.84, 95% CI 1.59–5.05), were more likely to have chronic hypertension (31.7% vs. 23.2%, OR 1.54, 95% CI 1.04–2.27), and had higher glucose levels at all three OGTT points. Multivariable logistic regression final model included age, BMI, previous GDM status, and the three OGTT values as predictors of insulin requirement. Conclusions We can use regularly collected data from patients (age, BMI, previous GDM status, and the three OGTT values) to calculate the risk of a woman with GDM diagnosed in OGTT needing insulin. Identifying patients with a greater risk of requiring pharmacological treatment could help healthcare services to better allocate resources and offer closer follow-up to high-risk patients.

Background: Multiple sclerosis (MS) is increasing in the pediatric population and, as in adults, symptoms vary among patients. In children the first manifestations can sometimes overlap with acute neurological symptoms. Urological symptoms have not been much studied in childhood. We shared our experience with MS urological manifestation in children. Methods: This article is a retrospective evaluation of all children with MS, according to the Krupp criteria, who also present with urological symptoms. We collected demographic and clinical history, the MR localization of demyelinating lesions, urological symptoms, and exams. Results: We report on six MS pediatric cases with urological manifestation. Urinary symptoms, characterized by urinary incontinence in five patients and urinary retention in one patient, appeared in a different time frame from MS diagnosis. Urodynamic exams showed both overactive and underactive bladder patterns. Treatment was defined according to lower urinary tract dysfunction, using clean intermittent catheterization, oxybutynin, and intradetrusor Onabotulinum Toxin-A injection. A low acceptance rate of invasive evaluation and urological management was observed. Conclusions: The MS diagnosis was traumatic for all our patients. We believe it is important to address urological care in young people from the time of diagnosis for prompt management; it could be useful to include a pediatric urologist in multidisciplinary teams.

This corrects the article published on Journal of Limnology 2022;81(s2):2136 (https://doi.org/10.4081/jlimnol.2022.2136 ). The Genbank accession numbers in the footnote of Table 1 are incorrect. The correct Table 1 footnote is: “PAN, Panperduto Dam; SL, Somma Lombardo; PV, Pavia; OG, Oglio River; *unique haplotypes, GenBank Acc. No. OQ676377-OQ676381.”

Freshwater ecosystems are heavily altered by human activities, with anthropic introductions of non-native species substantially contributing to their biotic degradation. The invasion by alien species can alter ecosystem balances with direct and indirect impacts across different levels of biotic organization. The number of invasive alien species is particularly high in Mediterranean fresh waters including rivers draining in the northern Adriatic basins. Here, the Padanian barbel Barbus plebejus endemic to the Padano-Venetian district, is threatened by the introduction of the European barbel Barbus barbus via competition and introgressive hybridization. In this study, we genetically characterised using the partial mitochondrial DNA Cytochrome b gene, barbels present in two main tributaries of the Po River, the lower Ticino and Oglio rivers where the two species are suspected to co-occur. Since the two river sections are highly regulated and present severe hydrological alterations caused by dams and other hydraulic structures, the aim of the study was to provide information on the barbel populations composition in these systems to foster the implementation of more suitable management plans aimed at the conservation of the native species. A total of 86 barbel have been analysed (50 in the Ticino River and 36 in the Oglio River) corresponding to 13 haplotypes of which 8 were phylogenetically attributed to B. barbus and five to B. plebejus. The high haplotypic diversity and the unimodal trend evidenced by the mismatch distribution analysis for B. barbus haplotypes support a potential demographic expansion. Altogether, these results highlighted that B. barbus is progressively expanding in northern Italy while posing a serious risk for the conservation of the native B. plebejus, stressing the need to actively focus ecosystem and fisheries management regulations to stop B. barbus from spreading further throughout northern Italy.

Abstract The Chilean Patagonia is a complex puzzle of numerous fjords, channels, bays, estuaries, and islands. The largest part of it is very remote, hampering the generation of scientific knowledge and effective management planning that could balance conservation of the marine resources with the increasing development of aquaculture activities. The present study focuses on the deep-water emergent cold-water coral Desmophyllum dianthus, dwelling in Chilean Patagonia, with the aim to illustrate its population genetic structure, demography and adaptation of the species along this coast. Microsatellite loci analysis included D. dianthus individuals from twelve sampling localities along bathymetric and oceanographic gradients from the latitude 40°S to 48°S. The results showed a lack of genetic structure with an asymmetric dispersion of individuals, and relevant heterozygosity deficiency in some populations. This study also analyses the natural and human impacts affecting the region (e.g., climate change, increasing salmon farming activities), and stresses the importance of including genetic information in the process of management and conservation of marine resources. In particular, the relevance of using interdisciplinary approaches to fill the gaps in scientific knowledge especially in remote and pristine areas of western Patagonia. Therefore, information on genetic spatial distribution of marine fauna could become pivotal to develop a holistic ecosystem-based approach for marine spatial planning.

Climate change along with the increasing exploitation of water resources exacerbates low-flow periods, causing detrimental effects on riverine communities. The main mitigation measure currently adopted to counteract hydrological alterations induced by off-stream diversion is the release of minimum flows (MFs), even if within the European Union Water Framework Directive an upgrade towards ecological flows is urgently required to achieve good ecological status (GES). In this study, we investigated the temporal evolution of the benthic macroinvertebrate community in an Italian-regulated lowland river (Ticino River) to clarify the ecological effects of summer low flows, and we evaluated the current MFs in the perspective of meeting GES standard. Biomonitoring was carried out for four consecutive years (2019-2022), in a river site immediately below a large off-stream diversion. The four study years were characterized by different streamflow patterns, thus allowing us to compare the temporal trajectories of the community under different flow conditions. Moreover, the interruption of the low-flow periods due to overflow spilled by the upstream dam gave us the opportunity to assess the effects of experimental flow peaks. Contrary to the expectation, the macroinvertebrate assemblage kept almost unvaried across the years, showing great resistance and resilience to hydrological changes. Even in extraordinarily dry 2022, the community composition varied only slightly, with a reduction of mayflies and an increase of mollusks. However, a deterioration of the ecological status below GES standard was recorded that summer, indicating the need for an upgrading of the current MFs. This upgrade would include experimental flow peaks in critical periods, which act as intermediate disturbances, enhancing community richness, diversity, and overall quality, as well as compliance with a threshold of an index specifically developed for the hydrological pressure.

Abstract Background Recognizing that hyperglycemia in pregnancy can impact both individually a patient’s health and collectively the healthcare system and that different levels of hyperglycemia incur different consequences, we aimed to evaluate the differences and similarities between patients who met the diagnostic criteria for gestational diabetes mellitus (GDM) or diabetes in pregnancy (DIP) according to the World Health Organization diagnostic criteria based on the 75 g oral glucose tolerance test (OGTT). Methods This retrospective study included a cohort of 1064 women followed-up at the Gestational Diabetes Unit of Hospital das Clinicas da Faculdade de Medicina da Universidade de Sao Paulo (Sao Paulo, Brazil). Patients were classified into GDM and DIP groups, according to their OGTT results. Their electronic charts were reviewed to obtain clinical and laboratory data for all participants. Results Women in the DIP group had a higher pre-pregnancy body mass index (30.5 vs 28.1 kg/m2, odds ratio [OR] 1.07, 95% confidence interval [CI] 1.02–1.11), more frequently experienced GDM in a previous pregnancy (25% vs. 11%, OR 2.71, 95% CI 1.17–6.27), and were more likely to have chronic hypertension (43.1% vs. 23.5%, OR 2.46, 95% CI 1.47–4.11), a current twin pregnancy (10.8% vs. 2.9%, OR 4.04, 95% CI 1.70–9.61), or require insulin (46.1% vs. 14.3%, OR 5.14, 95% CI 3.06–8.65) than those in the GDM group. Patients in the DIP group also had a higher frequency of large-for-gestational-age infants (12.3% vs. 5.1%, OR 2.78, 95% CI 1.23–6.27) and abnormal postpartum OGTT (45.9% vs. 12.6%, OR 5.91, 95% CI 2.93–11.90) than those in the GDM group. Nevertheless, in more than half of the DIP patients, glucose levels returned to normal after birth. Conclusions Diabetes in pregnancy is associated with an increased risk of adverse perinatal outcomes but does not equate to a diagnosis of diabetes post-pregnancy. It is necessary to identify and monitor these women more closely during and after pregnancy. Keeping patients with hyperglycemia in pregnancy engaged in healthcare is essential for accurate diagnosis and prevention of complications related to abnormal glucose metabolism.

Objective: To evaluate neurogenic bladder and bowel dysfunction (NBBD) in children with cerebral palsy (CP) and acquired brain injury (ABI), a condition considered less frequent in those patients than in children with spinal cord injury (SCI), and to study the relationship between NBBD and disability grade in this population. Study Design: We retrospectively reviewed the clinical data of all patients (aged 3–18 years old) admitted during a three-month observation in our neurorehabilitation department. Data collected were as follows: demographic parameters; disability status (Wee-FIM Scale, Gross Motor Function Classification System (GMFCS) and the Communication Function Classification System); and gastrointestinal and urological symptoms (diaries, Bristol scale, Pad Test and International Consultation on Incontinence Modular Questionnaire). Results: Sixty patients were enrolled (31 females, 29 males): 30 CP, 17 ABI, 3 SCI, and 10 others with neurological diseases. All presented urinary incontinence without gender differences. CP and ABI had major incidences of bowel dysfunction (50% and 64.7%, respectively) and SCI of urinary tract infections (66.6%) and enuresis (100%). A major incidence of symptoms was recorded in patients with higher GMFCS levels (level 3-4-5). Conclusions: NBBD has a high frequency in children with CP and ABI, as in SCI. More attention is needed from pediatricians and pediatric urologists for this clinical entity. Further studies are needed to better understand clinical relevance and, therefore, to establish specific management. [ABSTRACT FROM AUTHOR]

In the original publication [...]

Abstract. This article aims to introduce aspects involved in studies on migratory dynamics in the Middle East and North Africa (MENA). In this sense, we present some historical dynamics for defining the territories of what is considered the MENA region, as well as highlighting the participation of these countries in the context of the migratory and humanitarian crises that have characterized the dynamics of mobility in and in the region. In such a context, we draw attention to the politicization of migratory phenomena and to the still sparse study and research initiatives that analyze the migratory dynamics of countries in the MENA region to the global south. Finally, the article introduces the discussions on migrations in the MENA region that are part of this dossier, inviting the reader to dialogue with different theoretical-methodological approaches on the migration phenomenon in that context.

Posterior Urethral Valves (PUV) are the most common cause of lower urinary tract obstruction. More severe forms are detected early in pregnancy (mainly type I), while other forms are usually discovered later in childhood when investigating lower urinary tract symptoms. Bladder dysfunction is common and is associated with urinary incontinence in about 55% (0%–72%). Despite the removal of the obstruction by urethral valve ablation, pathological changes of the urinary tract can occur with progressive bladder dysfunction, which can cause deterioration of the upper urinary tract as well. For this reason, all children with PUV require long-term follow-up, always until puberty, and in many cases life-long. Therefore, management of PUV is not only limited to obstruction relief, but prevention and treatment of bladder dysfunction, based on urodynamic observations, is paramount. During time, urodynamic patterns may change from detrusor overactivity to decreased compliance/small capacity bladder, to myogenic failure (valve bladder). In the past, an aggressive surgical approach was performed in all patients, and valve resection was considered an emergency procedure. With the development of fetal surgery, vesico-amniotic shunting has been performed as well. Due to improvements of prenatal ultrasound, the presence of PUV is usually already suspected during pregnancy, and subsequent treatment should be performed in high-volume centers, with a multidisciplinary, more conservative approach. This is considered to be more effective and safer. Primary valve ablation is performed after clinical stability and is no longer considered an emergency procedure after birth. During childhood, a multidisciplinary approach (pediatric urologist, nephrologist, urotherapist) is recommended as well in all patients, to improve toilet training, using an advanced urotherapy program with medical treatments and urodynamic evaluations. The aim of this paper is to present our single center experience over 30 years.

Gaetano Zaccara,1 Simona Lattanzi,2 Antonio Leo,3 Emilio Russo3 1Regional Health Agency of Tuscany, Firenze, Italy; 2Neurological Clinic, Department of Experimental and Clinical Medicine, Marche Polytechnic University, Ancona, Italy; 3Science of Health Department, University Magna Grecia of Catanzaro, Catanzaro, 88100, ItalyCorrespondence: Gaetano ZaccaraRegional Health Agency of Tuscany, via Pietro Dazzi 1, Firenze, 50141, ItalyTel +39 055 2336851Email gaetanozaccara@yahoo.itAbstract: Cenobamate (CNB) is the latest antiseizure medication (ASM) authorized for the treatment of focal-onset seizures in adults. Although the precise mechanism of action of CNB is not yet fully understood, this drug inhibits the persistent, rather than transient, voltage-gated sodium channel currents and is a positive allosteric modulator of synaptic and extrasynaptic GABAA receptors, differently from benzodiazepines. CNB has a non-linear pharmacokinetic with a terminal half-life range of about 50/60 hours within the therapeutic dose range, which allows once daily administration. Cenobamate inhibits cytochrome P450 (CYP) 2C19 and induces CYP3A4 and 2B6, and hence can potentially interact with ASMs (eg, phenytoin, carbamazepine and clobazam) and no-ASMs drugs. In two randomized, double-blind, placebo-controlled trials in patients with focal epilepsies, CNB has shown a particularly good efficacy with a rate of seizure freedom of about 20% during the maintenance period in participants treated with the dose of 400 mg/day. The most common treatment-emergent adverse effects include central nervous system-related symptoms, like dizziness, diplopia, somnolence, and gait disturbances. Safety issues of particular interest are severe skin reactions (drug reaction with eosinophilia and systemic symptoms) and QT shortening, which contraindicates its use in subjects with familial short QT syndrome or in combination with other QT-shortening drugs. The recommended starting dose is 12.5 mg/day, which can be gradually titrated to the target dose (200 mg/day) and further increased up to 400 mg/day. There are several aspects of CNB that need to be still addressed, including the long-term efficacy and the efficacy in patients with generalized seizures. Ongoing studies will clarify these issues. The clinical relevance of the peculiar pharmacokinetics and the pattern of drug–drug interactions also require further investigation.Keywords: cenobamate, focal seizures, antiseizure medications, drug–drug interactions, safety, efficacy

The steel industry is one of the most energy-intensive sectors, as it requires a great amount of resources and produces a considerable quantity of by-products, with not negligible environmental impact. Therefore, the main challenge of steelworks consists in improving sustainability and reducing carbon footprint of the production process, by ensuring the required quality of final products. In this context, the reuse and recycling of by-products can play a key role in preventing their landfilling and waste of valuable products, reducing the exploitation of primary raw materials, decreasing CO2 emissions, and supporting the implementation of the Circular Economy concept. In particular, one of the main by-products is slag, which can be used as a potentially valuable source of secondary raw materials, leading to a substantial reduction of natural resources usage and related costs. This paper concerns part of the work developed inside the EU-funded project entitled “Optimising slag reuse and recycling in electric steelmaking at optimum metallurgical performance through on-line characterization devices and intelligent decision support system – iSlag”. The main focus of this project is the valorisation of slags produced in the electric steelmaking route, by defining good practices, investigating new recycling paths, and promoting industrial symbiosis solutions. In this paper, the adaptation and the improvement of a previously developed Aspen Plus® simulation model are presented to obtain an accurate prediction of slag features. In particular, the model estimates amount and composition of slags produced in the primary and the secondary steelmaking processes, and it allows simulating different case scenarios including usual and unusual conditions, for instance, process operating conditions, raw materials compositions, steel families to be produced. In addition to slag features, product compositions and environmental and energy impacts can be monitored with the model.

The highly polymorphic taxon European brown trout (genus Salmo) has high phenotypic plasticity, displaying a complex pattern of morphological and life-history variation, contributing to taxonomic confusion. Three main mitochondrial lineages (Adriatic, Mediterranean, and marmoratus) developed during the Pleistocene climatic events in the southern Alpine ecosystem. Here, the natural distribution of native brown trout S. trutta is controversial, complicated by introductions of the Atlantic strain. By investigating museum vouchers, this study aimed to retrace the historical presence of brown trout in the southern Alpine ecosystem before the beginning of mass introductions, which occurred since the middle of the 19th century. By examining the combination of historical and current genetic variability, this study aims to depict the actual impact of introductions of the introduced strain, increasing knowledge and informing conservation strategies and future management plans. The molecular approaches selected were: (i) sequencing of the mitochondrial control region and (ii) genotyping of the nuclear gene LDH-C1*. Vouchers dated the presence of the native Adriatic strain since 1821, while current genetic variability showed the widespread signature of introgression, a consequence of several decades of introductions. Focused plans to preserve local lineages are urgently needed, including short-term solution to avoid complete pauperization of this ecosystem.

Cells have evolved a robust and highly regulated DNA damage response to preserve their genomic integrity. Although increasing evidence highlights the relevance of RNA regulation, our understanding of its impact on a fully efficient DNA damage response remains limited. Here, through a targeted CRISPR-knockout screen, we identify RNA-binding proteins and modifiers that participate in the p53 response. Among the top hits, we find the m6A reader YTHDC1 as a master regulator of p53 expression. YTHDC1 binds to the transcription start sites of TP53 and other genes involved in the DNA damage response, promoting their transcriptional elongation. YTHDC1 deficiency also causes the retention of introns and therefore aberrant protein production of key DNA damage factors. While YTHDC1-mediated intron retention requires m6A, TP53 transcriptional pause-release is promoted by YTHDC1 independently of m6A. Depletion of YTHDC1 causes genomic instability and aberrant cancer cell proliferation mediated by genes regulated by YTHDC1. Our results uncover YTHDC1 as an orchestrator of the DNA damage response through distinct mechanisms of co-transcriptional mRNA regulation. Synopsis: The DNA damage response (DDR) is critical to preserve genomic integrity, and p53 plays a central role in this process. Here, we show that YTHDC1 controls the correct expression of TP53 mRNA as well as splicing of key DDR factors in a m6A-independent and -dependent manner, respectively. CRISPR knockout screening focused on RNA regulators identifies YTHDC1 as required for p53-dependent reporter gene activation. YTHDC1 directly controls TP53 expression through promoter-proximal RNAPII pause-release in a m6A-independent mechanism. In addition, YTHDC1 directly regulates the efficient splicing of ATR, BIRC6 and SETX transcripts in a m6A-dependent manner. Depletion of YTHDC1 results in accumulated DNA damage, reduced proliferation and tumorigenicity of lung cancer cells, caused by deregulation of DDR factors. m6A reader YTHDC1 contributes to genome integrity by promoting p53 expression and controling pre-mRNA splicing of key DNA damage response regulators. [ABSTRACT FROM AUTHOR]

Beluga sturgeon (Huso huso Linnaeus, 1758, acipenseridae) and Adriatic sturgeon (Acipenser naccarii, Bonaparte, 1836, acipenseridae) within the Po River basin have been recently assessed for the IUCN Red List of Threatened Species and were found to be Extinct in the Wild and Critically Endangered, respectively. Significant declines in both species' abundance have spurred major research efforts and management actions in recent decades. Recently, specific actions have been conducted to recover habitat connectivity through projects of river defragmentation and reintroduction plans have been implemented for both sturgeon species. To manage effective conservation efforts, knowledge of a species' distribution and abundance is critical, especially for adult sturgeon that are able to move hundreds of kilometers away from release sites. Here, two new quantitative PCR (qPCR) assays to detect beluga sturgeon and Adriatic sturgeon environmental DNA (eDNA) in water samples have been developed with the goal of providing an alternative method to monitor their presence. Two Taqman-based assays targeting the mitochondrial cytochrome b region were developed and showed no amplification of other related and co-occurring fishes. A mesocosm within the Ticino Park on the Ticino River (a main tributary of the Po River), where both species are bred, was used to develop and validate the assays. The LOQ for H. huso assay corresponded to Ct = 41 (7.33 × 107 DNA counts/µL of reaction) and for A. naccarrii it was Ct = 37 (2.23 × 1016 DNA counts/µL of reaction). Additionally, water samples were taken from the discard drainage, which flows directly into the Ticino River, testing positive detection of eDNA within a distance of up to 2 km. Overall, the results suggested that the two assays developed in this study could represent a promising new tool for monitoring both beluga and Adriatic sturgeon. [ABSTRACT FROM AUTHOR]

Rheumatoid arthritis (RA) is a systemic inflammatory disease, which primarily causes symmetric polyarthritis. An extrarticolar involvement is common, and the commonly involved organ is lungs. Although cardiac disease is responsible for most RA-related deaths, pulmonary disease is also a major contributor, accounting for ~10–20% of all mortality. Pulmonary disease is a common (60–80% of patients with RA) extra-articular complication of RA. Optimal screening, diagnostic, and treatment strategies of pulmonary disease remain uncertain, which have been the focus of an ongoing investigation. Clinicians should regularly assess patients with RA for the signs and symptoms of pulmonary disease and, reciprocally, consider RA and other connective tissue diseases when evaluating a patient with pulmonary disease of an unknown etiology. RA directly affects all anatomic compartments of the thorax, including the lung parenchyma, large and small airways, pleura, and less commonly vessels. In addition, pulmonary infection and drug-induced lung disease associated with immunosuppressive agents used for the treatment of RA may occur.