New olive-pomace fertilizer tested with a 2-tiers approach: Biomarkers on Eisenia fetida, physiochemical effects on Solanum lycopersicum and Olea europaea.

Every year, the olive oil industry generates a substantial amount of pomace, a semi-solid residue made up of skin, pulp, pit, and kernel fragments. Rather than being disposed of, the pomace can be dried and transported to an extraction facility where pomace oil can be extracted. Utilizing its high thermal capacity, the extracted pomace can be used as a supplementary fuel in the drying process, resulting in the production of ashes. In this study, the effect of pomace waste applied to the soil was investigated by testing two mixtures with different proportions of de-oiled pomace flour and kernel ash (50:50 and 70:30, respectively) in powder and pellet form. We used a dual approach, evaluating the effects of the mixtures on both soil communities and plant physiology and productivity, to assess the actual usability of the fertilizer in agriculture. The biomarker approach was valuable in assessing the sublethal effects of the two mixtures in powder form in soil. After 30 days of exposure, the bioindicator organism Eisena fetida showed lipid peroxidation, glutathione S-transferase and lactate dehydrogenase levels similar to the control, while lysozyme activity was reduced in all treatments. The powder mixture was lethal to the tomato plants, while there was no evidence of any damage to the olive trees. During 60 days of monitoring, both mixtures in pellet form showed a slight increase in physiological parameters, suggesting a benefit to the photosynthetic system. The improved carbon assimilation in tomato plants treated with the mixtures results in increased plant productivity, both in terms of number and weight of fruits, while maintaining the antioxidant content. This study paves the way for the use of the pomace mixture as a soil improver, thus increasing the value of this waste product.

Epileptic encephalopathies and progressive neurodegeneration.

Developmental encephalopathies (DE), epileptic encephalopathies (EE) and developmental and epileptic encephalopathies (DEE) are overlapping neurodevelopmental disorders characterized by early-onset, often severe epileptic seizures, developmental delay, or regression and have multiple etiologies. Classical nosology in child neurology distinguished progressive and nonprogressive conditions. A progressive course with global cognitive worsening in DEE is usually attributed to severe seizures and electroencephalographic abnormalities whose deleterious effects interfere with developmental processes both in an apparently healthy brain and in an anatomically compromised one. Next generation sequencing and functional studies have helped identifying and characterizing clinical conditions, each with a broad spectrum of clinical and anatomic severity corresponding to a variable level of neurodegeneration, such that both a rapidly progressive course and considerably milder phenotypes with no obvious deterioration can be configured with mutations in the same gene. In this mini review, we present examples of genetic DEE that draw connections between neurodevelopmental and neurodegenerative disorders.

Characteristics of viral pneumonia in the COVID-19 era: an update.

Influenza virus, rhinovirus, and adenovirus frequently cause viral pneumonia, an important cause of morbidity and mortality especially in the extreme ages of life. During the last two decades, three outbreaks of coronavirus-associated pneumonia, namely Severe Acute Respiratory Syndrome, Middle-East Respiratory Syndrome, and the ongoing Coronavirus Infectious Disease-2019 (COVID-19) were reported. The rate of diagnosis of viral pneumonia is increasingly approaching 60% among children identified as having community-acquired pneumonia (CAP). Clinical presentation ranges from mild to severe pneumonitis complicated by respiratory failure in severe cases. The most vulnerable patients, the elderly and those living with cancer, report a relevant mortality rate. No clinical characteristics can be useful to conclusively distinguish the different etiology of viral pneumonia. However, accessory symptoms, such as anosmia or ageusia together with respiratory symptoms suggest COVID-19. An etiologic-based treatment of viral pneumonia is possible in a small percentage of cases only. Neuraminidase inhibitors have been proven to reduce the need for ventilatory support and mortality rate while only a few data support the large-scale use of other antivirals. A low-middle dose of dexamethasone and heparin seems to be effective in COVID-19 patients, but data regarding their possible efficacy in viral pneumonia caused by other viruses are conflicting. In conclusion, viral pneumonia is a relevant cause of CAP, whose interest is increasing due to the current COVID-19 outbreak. To set up a therapeutic approach is difficult because of the low number of active molecules and the conflicting data bearing supportive treatments such as steroids.

Isolation, proliferation and characterization of endometrial canine stem cells.

In the last decade, progenitor cells isolated from dissociated endometrial tissue have been the subject of many studies in several animal species. Recently, endometrial cells showing characteristics of mesenchymal stem cells (MSC) have been demonstrated in human, pig and cow uterine tissue samples. The aim of this study was the isolation and characterization of stromal cells from the endometrium of healthy bitches, a tissue that after elective surgery is routinely discarded. Multipotent stromal cells could be isolated from all bitches enrolled in the study (n = 7). The multipotency of cells was demonstrated by their capacity to differentiate into adipocytic, osteocytic and chondrocytic lineages. Clonogenicity and cell proliferation ability were also tested. Furthermore, gene expression analysis by RT-PCR was used to compare the expression of a set of genes (CD44, CD29, CD34, CD45, CD90, CD13, CD133, CD73, CD31 CD105, Oct4) with adipose tissue-derived MSC. Stromal cells isolated from uterine endometrium showed similar morphology, ability of subculture and plasticity, and also expressed a panel of genes comparable with adipose tissue-derived MSC. These data suggest that endometrial stromal cells fulfil the basic criteria proposed by the "Mesenchymal and Tissue Stem Cell Committee of the International Society for Cellular Therapy" for the identification of mesenchymal stem cells. Although endometrial mesenchymal stem cells (EnMSC) showed a lower replicative ability in comparison with adipose tissue-derived MSC, they could be considered a cell therapeutic agent alternative to adipose tissue or bone marrow-derived MSC in dog.

Focal dysplasia of the cerebral cortex and infantile spasms associated with somatic 1q21.1-q44 duplication including the AKT3 gene.

Somatic and germline duplications or activating mutations of AKT3 have been reported in patients with hemimegalencephaly and megalencephaly. We performed array comparative genomic hybridization on brain tissue and blood in 16 consecutive patients with symptomatic epilepsy due to focal or multilobar malformations of cortical development who underwent surgical treatment of epilepsy. One patient with infantile spasms and a dysplastic left frontal lobe harboured a somatic trisomy of the 1q21.1-q44 chromosomal region, encompassing the AKT3 gene, in the dysplastic brain tissue but not in blood and saliva. Histopathology revealed severe cortical dyslamination, a thin cortex in the premotor area with microgyri and microsulci, immature neurons with disoriented dendrites and areas of cortical heterotopia in the sub-cortical white matter. These cytoarchitectural changes are close to those defining type Ib focal cortical dysplasia. Immunohistochemistry in brain specimens showed hyperactivation of the PI3K/AKT/mTOR pathway. These findings indicate that AKT3 upregulation may cause focal malformations of cortical development. There appears to be an etiologic continuum between hemimegalencephaly and focal cortical dysplastic lesions. The extent of brain malformations due to AKT3 upregulation may be related to the embryonic stage when the post-zygotic gene alteration occurs.

Adverse cardiovascular events associated with triptans and ergotamines for treatment of migraine: systematic review of observational studies.

BACKGROUND: Apart from the underlying cardiovascular (CV) risk associated with migraine, both triptans and ergotamines can induce vasoconstriction and potentially increase the risk of serious ischemic events. Because of the low frequency of such events in eligible patients, randomized controlled trials are not exhaustive to assess the drug-related CV risk. Observational studies are, therefore, an essential source of information to clarify this matter of concern. AIM: The aim of this study was to systematically review the available published observational studies investigating the risk of serious CV events in triptan or ergotamine users, as compared to unexposed migraineur controls. METHODS: We systematically searched MEDLINE and EMBASE electronic databases for cohort or case-control studies up to December 1, 2013. Studies retrieved from CDSR, DARE and HTA databases of the Cochrane Library were used for snowballing. Studies investigating the risk of any CV outcome in patients with a migraine diagnosis and exposed to triptans or ergotamines were considered for inclusion. Selection of studies, data extraction, and risk of bias assessment were conducted independently by two reviewers. Pooled odds ratios (ORs) with 95% confidence interval (95% CI) were computed using a random-effects model for studies and outcomes judged eligible for quantitative data synthesis. RESULTS: From a total of 3370 citations retrieved, after duplicate removal and screening, only four studies met the inclusion criteria (three nested case-control analyses and one retrospective cohort study). These studies investigated the risk of different CV outcomes associated with either the recency or the intensity of exposure to the studied drugs. As for the intensity of use, the pooled OR of serious ischemic events was 2.28 (95% CI 1.18-4.41; I (2 )= 0%) for ergotamine use (two studies), whereas for triptans (three studies) it was 0.86 (95% CI 0.52-1.43; I (2 )= 24.5%). Recent use of ergotamines was not significantly associated with any CV outcome (only one available study). Two studies investigated the risk of stroke related to recent triptan use: the first study reported an OR of 0.90 (0.64-1.26), and the second one suggested an increased risk of 2.51 (1.10-5.71). In this case, because of the high degree of heterogeneity, results were not pooled. CONCLUSIONS: To date, few comparative observational studies have investigated the CV safety of migraine-specific drugs in clinical practice. Evidence gathered here suggests that intense consumption of ergotamines may be associated with an increased risk of serious ischemic complications. As for triptans, available studies do not suggest strong CV safety issues, although no firm conclusions can be drawn. In particular, evidence on stroke risk is conflicting. However, if an increase of the absolute stroke risk in recently exposed patients does actually exist, it must be small. Overall, residual uncontrolled confounding factors reduce the confidence in the risk estimates collected from the included studies. Further investigations are needed to better define the risk for rare but serious CV events related to triptan and ergotamine use for treatment of migraine.

High prevalence of gluten sensitivity in a cohort of patients with undifferentiated connective tissue disease.

OBJECTIVES: The aim of this study was to investigate if co-morbid conditions as hepatitis C virus infection and celiac disease may be associated to undifferentiated connective tissue disease. METHODS: We studied retrospectively and prospectively 52 patients with diagnosis of undifferentiated connective tissue disease, subdivided, according to Vaz criteria, in systemic lupus erythematosus, systemic sclerosis and Sjögren's syndrome-like subgroups. Serological markers of celiac disease as anti-gliadin, anti-endomysium and anti-tissue transglutaminase antibodies were investigated. An esophagogastroduodenoscopy with duodenal biopsy and histological examination was proposed to patients with positive celiac disease serology. In addition antibodies directed to hepatitis C virus and total IgA-antibodies were investigated. RESULTS: Six patients (11,5%) were positive for celiac disease serological tests although two of them were asymptomatic. Four patients underwent an esophagogastroduodenoscopy, showing total or subtotal villous atrophy at duodenal biopsies. Hepatitis C virus serology was negative in all patients and none had IgA deficiency. 83% of celiac patients showed a scleroderma-like phenotype. We observed a statistically higher incidence of autoimmune symptoms in patients with gluten sensitivity. Fatigue and myalgia regressed early after the beginning of gluten-free diet. CONCLUSIONS: In our cohort of patients the prevalence of celiac disease was higher than that reported in the general population. We believe that all patients with diagnosis of undifferentiated connective tissue disease, especially those with a systemic sclerosis-like presentation, should be investigated for celiac disease, even in absence of gastrointestinal symptoms. Gluten-free diet should be early recommended to all patients having undifferentiated connective tissue disease and gluten sensitivity.

Comparative safety profiles of intravitreal bevacizumab, ranibizumab and pegaptanib: the analysis of the WHO database of adverse drug reactions.

PURPOSE: The purpose of this study is to conduct a comparative analysis of the suspected adverse drug reactions (ADRs) associated with intravitreal bevacizumab, ranibizumab and pegaptanib in the WHO database in order to have a real-life information on these drugs, which now is only based on data coming from clinical trials. METHODS: ADR reports for intravitreal use of bevacizumab, ranibizumab and pegaptanib from January 2002 to December 2012 were selected from the WHO-VigiBase. Reporting odds ratio (ROR) with confidence interval of 95 % and p value was calculated. The analysis was performed for drug-reaction pairs. The Medical Dictionary for Regulatory Activities (MedDRA) terminology for ADRs was used. RESULTS: The analysis was performed on 3180 reports corresponding to 7753 drug-reaction pairs. Significant RORs for endophthalmitis and uveitis (1.90, 95 % confidence interval (CI) 1.48-2.43, and 10.62, 6.62-17.05, respectively) were retrieved for bevacizumab, and cerebrovascular accident and myocardial infarction produced significant ROR (1.54, 1.14-2.10 and 1.73, 1.18-2.53, respectively) for ranibizumab. Pegaptanib was significantly associated with visual impairment (1.98, 1.12-3.5, p = 0.02), nausea (3.29, 1.57-6.86, p < 0.001), vomiting (2.91, 1.2-7.07, p = 0.01) and drug hypersensitivity (8.75, 3.1-24.66, p < 0.001). CONCLUSIONS: Our data showed an elevated disproportionality for cardiovascular ADRs in patients treated with ranibizumab and for infective ocular reactions in those treated with bevacizumab. No relevant safety issues were identified for pegaptanib. These findings suggest bevacizumab as a suitable choice for AMD therapy due to its effectiveness similar to that of ranibizumab, its favourable safety profile and for its lower cost.

COPD and thyroid dysfunctions.

BACKGROUND: Chronic obstructive pulmonary (COPD) is one of the major causes of morbidity and mortality in the world. COPD is characterized by chronic inflammation in the pulmonary compartment and in the systemic circulation. This disorder is associated with clinically significant alterations in biochemistry and organ function; thyroid dysfunctions are common in chronic diseases, such as COPD. Several characteristics of COPD patients could increase their likelihood of developing hypothyroidism or hyperthyroidism. The purpose of our study was to assess the impact of thyroid dysfunction in patients with COPD. METHODS: We evaluated the pulmonary function tests, arterial blood gases, maximal inspiratory pressure (MIP), maximal expiratory pressure (MEP), and thyroid functions in patients with COPD, recruited between admissions in Respiratory Diseases Unit, Policlinico Umberto I, Rome, Italy, from June 2012 to May 2013. We selected patients with subclinical hypothyroidism (ScH), overt hypothyroidism, and hyperthyroidism, and a control group without thyroid disturbance. RESULTS: Our results indicate that patients with overt hypothyroidism have lower levels of pO2, MIP, and MEP compared with subjects with ScH, hyperthyroidism, and the control group. We also found a substantial tendency towards pCO2 levels increase in patients with hypothyroidism (p = 0.06). CONCLUSIONS: Patients with thyroid dysfunctions have a greater impairment of MIP and MEP and a negative correlation was observed between hypoxemia and TSH. Further studies are needed to investigate whether the treatment of thyroid disfunction could have a beneficial effect on COPD patients' lung function and prognosis.

A long-term retrospective clinical study on MTA pulpotomies in immature permanent incisors with complicated crown fractures.

AIM: The study was undertaken to evaluate mineral trioxide aggregate (MTA) clinically and radiographically as a pulpotomy agent in immature permanent teeth whose pulps were exposed by a complicated crown fracture. MATERIALS AND METHODS: Thirty incisors with exposed pulps in twenty-nine patients were examined for this retrospective study. According to exclusion criteria, only twenty-seven teeth were selected. Each tooth was treated with partial pulpotomy and the wounded pulp was covered with mineral trioxide aggregate. The children were recalled for clinical and radiographic evaluation at 3 months, 6 months, at approximately 12 months and 36 months. RESULTS: Out of 27 cases, 22 were categorized as 'healed' and 1 as 'healing'. The remaining 4 ones highlighted persistent disease and needed further endodontic treatment. CONCLUSION: MTA partial pulpotomy is an effective treatment in maintaining pulpal vitality and allowing physiological root development (apexogenesis).

ZeroExpander® effectiveness assessment in PEEK or PA12 in a group of paediatric patients with transverse maxillary deficiency.

AIM: The aim of this article is to compare the performance of ZeroExpander® realised using PEEK or PA12 for the expansion of the maxilla in paediatric patients, exploring a new concept for approaching maxillary expansion with a metal-free fixed automatic appliance, based on pre-programmed set-up and anchored on deciduous teeth. MATERIALS: It is a retrospective comparative study with a sample of 40 children in early or mixed deciduous dentition and transversal maxillary deficit, 20 treated with ZeroExpander® in PEEK and 20 treated with ZeroExpander® in PA12 with a mean age of 7.3 years old. The intraoral scans at T0 and at the end of the expansion were all performed by the same operator to obtain digital models on which were performed measurements by two other different operators. A descriptive analysis was conducted using frequencies and percentages for nominal variables and means and standard deviations for continuous variables. CONCLUSION: In cases of allergy or hypersensitivity to metals or to specific chronic or acute pathological conditions, which may require periodic magnetic resonance imaging (MRI), it may not be possible to use traditional and metal fixed expansion devices. Moreover the concept of autonomous driving in paediatric orthodontics is not only possible, but it is and will be more real and very useful in the future. The "ortho-paediatric dentistry concept" will increase the range of benefits for children and their families which, in addition to care and thanks to technology, demand well-being, safety, comfort and quality of life beyond clinics.

Splenic marginal zone lymphoma in a HIV-1 infected patient: evidence favouring a pathogenetic role of HIV-1 itself in the lymphomagenesis.

A rare case of splenic marginal zone lymphoma (SMZL) in a human immunodeficiency virus (HIV)-1 infected patient is described. As an association between SMZL and viral infections has been reported, the presence of the hepatitis C virus and HIV-1 genomes was evaluated. Only HIV-1 DNA levels were detected in enriched splenic B lymphocytes, suggesting a HIV-1 involvement in lymphomagenesis.

Allogeneic adipose tissue-derived mesenchymal stem cells in combination with platelet rich plasma are safe and effective in the therapy of superficial digital flexor tendonitis in the horse.

Overstrain tendonitis are common pathologies in the sport horses. Therapeutic approaches to tendon healing do not always result in a satisfactory anatomical and functional repair, and healed tendon is often characterized by functional impairment and high risk of reinjury. Recently, mesenchymal stem cells (MSCs) and platelet rich plasma (PRP) have been proposed as novel therapeutic treatments to improve the tendon repair process. MSCs are multipotent, easy to culture and being originated from adult donors do not pose ethical issues. To date, autologous MSCs have been investigated mainly in the treatment of large bone defects, cardiovascular diseases, osteogenesis imperfecta and orthopaedic injuries both in human and veterinary medicine. The clinical applications in which autologous MSCs can be used are limited because patient-specific tissue collection and cell expansion require time. For clinical applications in which MSCs should be used right away, it would be more practical to use cells collected from a donor, expanded in vitro and banked to be readily available when needed. However, there are concerns over the safety and the efficacy of allogeneic MSCs. The safety and efficacy of a therapy based on the use of allogeneic adipose tissue-derived mesenchymal stem cells (ASCs) associated to platelet rich plasma (PRP) were evaluated in 19 horses affected by acute or subacute overstrain superficial digital flexor tendonitis (SDFT). The application of allogeneic ASCs neither raised clinical sign of acute or chronic adverse tissue reactions, nor the formation of abnormal tissue in the long-term. After a follow-up of 24 months, 89.5% horses returned to their previous level of competition, while the reinjury rate was 10.5%, comparable to those recently reported for SDFT treated with autologous bone marrow derived MSCs. This study suggests that the association between allogeneic ASCs and PRP can be considered a safe and effective strategy for the treatment of SDF tendonitis in the horse.

Common variable immunodeficiency - new insight into the pathogenesis and the quest for a workable classification.

In this editorial we argue that more and more complex classifications for patients with common variable immunodeficiency (CVID) fail to identify those patients at high risk of developing infections. We propose that the minimal requirement to identify such patients is the absolute numbers of total and memory B cells and the IgM response to immunization with polysaccharides. If these data should be confirmed, they will provide the basis for a good classification of a heterogeneous group of patients. This simple, workable classification may result in a clinically useful identification of patients prone to more aggressive infections.

Increased large artery intima media thickness in adolescents with either classical or non-classical congenital adrenal hyperplasia.

BACKGROUND: Increased artery intima-media thickness (IMT) was found in adults with classical congenital adrenal hyperplasia (CAH). No data are available in patients with non-classical (NC) CAH. AIMS: To evaluate IMT in adolescents with classical and NC CAH and to compare the results with those recorded in a control population. PATIENTS AND METHODS: Eighteen adolescents with either classical (Subgroup A1) or NC CAH (Subgroup A2) were compared with 16 controls (Group B). All subjects underwent IMT ultrasonography measurement at different sites; results were correlated with clinical, metabolic, and insulin resistance (IR) data. RESULTS: When compared with Group B, both subgroups exhibited higher IMT values at all sites. No differences were found between classical and NC CAH. Univariate analysis of factors impacting on IMT of CAH patients demonstrated that: a) abdominal aorta (AA) IMT was positively correlated with cumulative glucocorticoid doses, triglyceride serum levels, and diastolic blood pressure SD score and negatively with androstenendione and ACTH levels; b) common carotid (CC) IMT was positively associated with triglycerides and triglyceride/HDL ratio. At multiple regression analysis, the independent positive predictors of AA and CC IMT were respectively triglyceride levels and triglyceride/HDL ratio. CONCLUSIONS: a) Even adolescents with NC CAH and not only those with classical form may be at higher risk of artery alterations; b) this risk is not necessarily associated with either obesity or waist/height ratio or dyslipidemia; c) an important role in the pathogenesis of artery alterations in CAH may be played by intermittent iatrogenic hypercortisolism and secondary IR.

An "alternative" clinical course of COPD exacerbation and pulmonary embolism.

Patients with chronic diseases, such as Chronic Obstructive Pulmonary Disease (COPD) and diabetes mellitus, are exposed to particular complications that require a careful diagnostic algorithm. Pulmonary Embolism (PE) in COPD patients often demands an accurate differential diagnosis and a prompt therapeutic intervention. Aspergillus spp. infection comprises a large spectrum of pathological manifestations, depending on immune status and the presence of underlying lung disease. These manifestations may range from invasive pulmonary aspergillosis (IPA) in gravely immunocompromised patients, to chronic necrotizing aspergillosis (CNA) in patients with chronic lung diseases and moderately compromised immune systems. Aspergilloma is generally observed in patients with cavitary lung diseases, and allergic bronchopulmonary aspergillosis (ABPA) is reported in patients with hypersensitivity to Aspergillus antigens. We report a case with pulmonary aspergillosis arisen on a pulmonary infarction after PE in a patient with COPD and diabetes mellitus. To date, report with this clinical evolution was not reported in literature. This report is intended to describe an accurate diagnostic path in a complex overlap of different pathological conditions, highlighting the great importance of differential diagnosis and an appropriate diagnostic algorithm. In addition, open issues on the real diagnostic value of clinical, radiological, and laboratory features for COPD exacerbation, PE and aspergillosis have been discussed.

Myxoid glioneuronal tumor: Histopathologic, neuroradiologic, and molecular features in a single center series.

BACKGROUND: Myxoid glioneuronal tumor (MGT) is a benign glioneuronal neoplasm recently introduced in the World Health Organization (WHO) classification of the central nervous system (CNS) tumors. MGTs are typically located in the septum pellucidum, foramen of Monro or periventricular white matter of the lateral ventricle. They were previously diagnosed as dysembryoplastic neuroepithelial tumors (DNT), showing histological features almost indistinguishable from classical cortical DNT. Despite that, MGTs have been associated with a specific dinucleotide substitution at codon 385 in the platelet-derived growth factor receptor alpha (PDGFRA) gene, replacing a lysine residue with either leucine or isoleucine (p. LysK385Leu/Iso). This genetic variation has never been described in any other CNS tumor. MATERIALS AND METHODS: Thirty-one consecutive tumors, previously diagnosed as DNTs at the Meyer Children's Hospital IRCCS between January 2010 and June 2021 were collected for a comprehensive study of their clinical, imaging, pathological features, and molecular profile. RESULTS: In six out of the thirty-one tumors we had previously diagnosed as DNTs, we identified the recurrent dinucleotide mutation in the PDGFRA. All six tumors were typically located within the periventricular white matter of the lateral ventricle and in the septum pellucidum. We then renamed these lesions as MGT, according to the latest WHO CNS classification. In all patients we observed an indolent clinical course, without recurrence. CONCLUSION: MGT represent a rare but distinct group of neoplasm with a typical molecular profiling, a characteristic localization, and a relative indolent clinical course.

A sequence variation in 3'UTR of CYP21A2 gene correlates with a mild form of congenital adrenal hyperplasia.

BACKGROUND: Congenital adrenal hyperplasia (CAH) is mainly caused by the deficiency of the 21-hydroxylase enzyme coded by the CYP21A2 gene. However, some alleles in the non-classical form (NC-CAH) remain without identified mutations, suggesting the involvement of regulatory regions. AIM: Our objective was to study an allele carrying the variant *13 G>A in the 3'UTR of the CYP21A2 gene identified in some patients with a mild form of NC-CAH in order to verify the possible implication of this variation with the phenotype observed. SUBJECTS AND METHODS: Among all the subjects in whom the CYP21A2 gene was analyzed, 14 patients and 7 relatives heterozygous or homozygous for the *13 G>A substitution in 3'UTR were selected. Sequencing of DNA, genotyping, multiplex ligation-dependent probe amplification (MLPA), in vitro studies and bioinformatic analysis were performed. RESULTS: The haplotype of the *13 G>A allele was identical in all the subjects with a monomodular structure composed by one C4A gene and one CYP21A2 gene without a second module with the CYP21A1P pseudogene. No other concomitant mutations were found in the region extending from 3 kb in the promoter and encompassing the polyadenylation signal. Both bioinformatic analysis and in vitro studies predicted an alteration of the RNA folding and expression, but no miRNA target sequences were found in this region. CONCLUSIONS: The identification of a substitution in the 3'UTR of the gene associated with a mild form of NC-CAH suggests the importance of analyzing the CYP21A2 untranslated regions to better characterize and treat this subgroup of patients.

A woman with a solitary pulmonary nodule: is it a lung cancer?

BACKGROUND: Solitary pulmonary nodules present a real challenge for physicians. Due to the clinical implications and prognosis of a certain diagnosis, it should be pursued with any cost; a clear definition is not always simple and further investigations are often necessary to exclude the possibility of a malignancy. A diagnostic path must be followed and the clinical hypothesis should be reconsidered on the basis of the new information provided by the tests, always keeping in mind their limits! Sometimes only the surgical resection permits a definitive diagnosis. A 68 year-old non-smoker female with a pulmonary solitary nodule highly suspicious to be malignant at the chest CT, performed a FBS with BAL, negative for neoplastic cells and for infective agents, and a CT guided pulmonary biopsy that was inconclusive. The patient underwent then a video-thoracoscopic atypical lung resection that demonstrated the reactive nature of the lesion, definitely excluding the presence of a malignancy.

A thoracic mass infiltrating the chest wall.

A case of thoracic mass infiltrating the chest wall mimicking a pulmonary invasive neoplasm is reported. Differential diagnosis and characteristic radiological and histological imaging had a decisive role in the case management. Actinomycosis is caused by a gram-positive, filamentous, microaerophilic bacteria. About 15% of the infections caused by Actinomyces involve the thorax. If not promptly diagnosed and treated thoracic actinomycosis may determine contiguous and systemic involvement. Actinomycosis is an anaerobic-to-microaerophilic bacteria and direct identification and isolation are difficult to obtain. In depth discussion diagnostic and therapeutic features are described in this report.