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The gestational period is a sensitive time marked by significant changes that can affect women's sleep and dreaming processes, with an augmented frequency and recall of dreams suggesting that dreaming represents an adaptive mechanism of emotional regulation. This study investigates the relationship between pregnancy-related variables, alexithymia, and depressive symptoms in influencing dream characteristics in women during the first trimester of pregnancy. A total of 118 pregnant women were recruited at the Obstetric Outpatient Service of an Italian University Hospital and completed the Mannheim Dream Questionnaire, the Toronto Alexithymia Scale-20, and the Edinburgh Postnatal Depression Scale. Regression analysis, t-test, and moderation analysis were conducted through Jamovi. Dream recall frequency was predicted by age, parity, and depressive symptoms. Nightmare frequency and lucid dream frequency were significantly predicted by depressive symptoms, while nightmare distress was predicted by an unplanned pregnancy. Alexithymia was linked to higher nightmare frequency and nightmare distress. Moderation analysis revealed that the presence of depressive symptoms predicted increased nightmare frequency only in women with higher levels of alexithymia. These findings highlight the role of emotional regulation in dreaming during pregnancy, particularly among women exhibiting alexithymic traits and depressive symptoms. Nightmare frequency may serve as an indicator of impaired emotional regulation, emphasising the need for targeted interventions to enhance emotional coping strategies in this population. Future research should examine the content of nightmares to further understand their implications for maternal mental health., (© 2024 The Author(s). Journal of Sleep Research published by John Wiley & Sons Ltd on behalf of European Sleep Research Society.)

Only few allergens derived from house dust mite (HDM) species have been evaluated in terms of their potential to induce allergic inflammation. In this study, we aimed to evaluate different aspects of the allergenicity and allergenic activity of Blo t 2, a Blomia tropicalis allergen. Blo t 2 was produced as a recombinant protein in Escherichia coli . Its allergenic activity was tested in humans by skin prick test and basophil activation assays, and in mice, by passive cutaneous anaphylaxis and a model of allergic airway inflammation. Sensitization rate to Blo t 2 (54.3%) was similar to that found to Blo t 21 (57.2%) and higher than to Der p 2 (37.5%). Most Blo t 2-sensitized patients showed a low intensity response (99.5%). Blo t 2 elicited CD203c upregulation and allergen induced skin inflammation. Additionally, immunized animals produced anti-Blo t 2 IgE antibodies and passive transfer of their serum to non-immunized animals induced skin inflammation after allergen exposure. Immunized animals developed bronchial hyperreactivity and a strong inflammatory lung reaction (eosinophils and neutrophils). These results confirm the allergenic activity of Blo t 2 and supports its clinical relevance.

Background: The management of patients with "Atypical Squamous Cells" (ASC) in conventional papanicolaou smears (CPS) is based on the risk of high-grade squamous intraepithelial lesion (HSIL). The efficacy of liquid-based cytology (LBC) to detect this premalignant lesion is variable, with little evidence of its performance in Colombian patients., Aims: The aim of this study is to determine the performance of LBC in the detection of premalignant lesions, in patients with ASC in CPS., Materials and Methods: Were obtained patients who attended colposcopy clinic due the result of ASC in CPS. An LBC was taken, which was interpreted by two pathologists without access to other results. The performance of LBC to detect HSIL, was determined, considering as a gold standard: histopathological study/negative-satisfactory colposcopy., Results: Were included 114 patients, with a mean age of 38.4 years (SD ± 13.3). LBC had abnormal results in 40.36% (n = 46), with a slightly higher proportion of low-grade squamous intraepithelial lesion (LSIL) than HSIL. The total of abnormal diagnoses by colposcopy and/or biopsy was 51.75% (n = 59), with a predominance of LSIL (36.84%). The sensitivity of the liquid-based cytology to detect premalignant lesions was 76.5%, specificity: 66.0%, positive predictive value: 28.3% and negative predictive value: 94.1%; The Cohen's kappa index of LBC for detecting HSIL was 0.2492 for the total population and 0.2907 for ≥30 years., Discussion: Although LBC decreases abnormal cytology and increases the detection of HSIL, which improves diagnostic accuracy; sensitivity and predictive values for detecting HSIL are not significantly different between CPS and LBC., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Journal of Cytology.)

The potential of LacI/P trc , XylS/P m , AlkS/P alkB , CprK/P DB3 and ChnR/P chnB regulatory nodes, recruited from both Gram-negative and Gram-positive bacteria, as the source of parts for formatting expression cargoes following the Standard European Vector Architecture (SEVA) has been examined. The five expression devices, which cover most known regulatory configurations in bacteria were assembled within exactly the same plasmid backbone and bearing the different functional segments arrayed in an invariable DNA scaffold. Their performance was then analysed in an Escherichia coli strain of reference through the readout of a fluorescence reporter gene that contained strictly identical translation signal elements. This approach allowed us to describe and compare the cognate expression systems with quantitative detail. The constructs under scrutiny diverged considerably in their capacity, expression noise, inducibility and ON/OFF ratios. Inspection of such a variance exposed the different constraints that rule the optimal arrangement of functional DNA segments in each case. The data highlighted also the ease of standardizing inducer-responsive devices subject to transcriptional activation as compared to counterparts based on repressors. The study resulted in a defined collection of formatted expression cargoes lacking any cross talk while offering a panoply of choices to potential users and help interoperability of the specific constructs., (© 2022 The Authors. Microbial Biotechnology published by Society for Applied Microbiology and John Wiley & Sons Ltd.)

This study was designed to explore learning experiences of university students with dyslexia and factors that could contribute to their success in the university career. Although, great efforts have been made to diagnose dyslexia and to mitigate its effects at primary and secondary school, little has been done at the university level in particular in the Italian context. Indeed in the university context, the availability and possibility to use of support tools, that enable the student to achieve educational success, is still not sufficiently adequate. In this paper we used bivariate association tests and cluster analysis, in order to identify the most suitable compensatory tools and support strategies that can facilitate the students' performance in higher education. The data were obtained through the voluntary participation of Italian students, enrolled in a bachelor degree course, with certified diagnosis of dyslexia. Six groups of students were identified from the cluster analysis, defining specific support tools and learning strategies for each group. Furthermore, through the creation of these six groups, it was possible to describe "profiles" that highlight the risk factors (late diagnosis) and-or protection factors (such as associations, support from friends and family) in analyzing the academic career of students with dyslexia. Therefore, starting from these data, through artificial intelligence it will be possible to identify and suggest study methodologies and create specific support tools for each student that can enable her/him to achieve educational success in her/his academic career., (© 2022. The Author(s).)

Kounis syndrome (KS) is a coronary syndrome in the setting of allergic/anaphylactic reactions and can be classified in three variants: vasospastic allergic angina (type I), allergic myocardial infarction (type II) and stent thrombosis (type III). The early diagnosis is of paramount importance for the correct management and the prognosis, being KS a life-threatening emergency condition. KS is not uncommon, but it is frequently unrecognized or undiagnosed in virtue of its broad clinical manifestations. The diagnosis should be based on the combination of cardiovascular and allergic/anaphylactic clinical symptoms and signs, as well as on laboratory, electrocardiographic, echocardiographic, and angiographic evidence. ECG monitoring, cardiac enzymes and troponin are mandatory to confirm or exclude KS in a patient with subclinical or clinical, acute or chronic allergic reactions. Nevertheless, the treatment is a real challenge for the emergency clinicians because guidelines have not been established yet, and the therapy is based on the variant type. We herein report the case of type I KS in a woman with no prior history of allergy, admitted to our emergency department for abdominal pain, nausea and hematochezia. Starting from this case we conducted a systematic search of the following databases: PubMed, Google Scholar, Science Direct, Medline, using the keywords of "Kounis syndrome", "coronary spams", "cardiac arrest", "sudden death", "allergy", and "anaphylaxis". The main purpose of this review is to remind emergency clinicians to keep a high index of suspicion regarding KS when dealing with patients with allergic reactions or anaphylaxis to promptly identify and correctly manage KS.

We prove the existence of at least one integrated solution to an impulsive Cauchy problem for an integro-differential inclusion in a Banach space with a non-densely defined operator. Since we look for integrated solution we do not need to assume that A is a Hille Yosida operator. We exploit a technique based on the measure of weak non-compactness which allows us to avoid any hypotheses of compactness both on the semigroup generated by the linear part and on the nonlinear term. As the main tool in the proof of our existence result, we are using the Glicksberg-Ky Fan theorem on a fixed point for a multivalued map on a compact convex subset of a locally convex topological vector space. This article is part of the theme issue 'Topological degree and fixed point theories in differential and difference equations'.

Objective: This study evaluated the ability of mid-regional proadrenomedullin (MR-proADM) to identify disease severity in Coronavirus disease 2019 (COVID-19) patients in comparison to conventional inflammatory biomarkers and clinical scores., Patients and Methods: In an observational trial, COVID-19 acute respiratory distress syndrome (ARDS) patients were enrolled. MR-proADM, C-reactive protein (CRP), procalcitonin (PCT) and lactic acid (LA) were measured in all patients at admission (T0), at 24 hours (T1) and in the third (T3) and fifth day (T5) of hospitalization. The aims of this study were to determine the role of MR-proADM to detect patients with high risk of mortality and compare the prognostic value of MR-proADM with commonly used clinical scores (Sequential Organ Failure Assessment score - SOFA score, Acute Physiologic Assessment and Chronic Health Evaluation II score - APACHE II score, and Simplified Acute Physiological score II - SAPS II score)., Results: Twenty-one COVID-19 ARDS patients admitted to the Intermediate Care Unit (IMCU) were enrolled. The median MR-proADM values were 2.28, 2.41, 1.96 and 1.89 nmol/L at T0, T1, T3 and T5, respectively. The 30-day all-cause mortality rate was 52.4%. Mean MR-proADM T0 value was significantly higher in non-survivors compared with survivors (3.5 vs. 1.1 nmol/L, p < 0.05). No significant differences were found for the other inflammatory biomarkers. In terms of the area under the receiver-operating characteristic curve (AUC), MR-proADM showed a similar discriminatory power compared with APACHE II, SOFA and SAPS II score (0.81, 0.91, 0.70 and 0.78, respectively). The optimal MR-proADM cut-point cut-off point was 1.07 nmol/L, which corresponds to a sensitivity of 91% and a specificity of 71%., Conclusions: MR-proADM, in addition to the clinical scores, could be useful to predict outcome in COVID-19 ARDS patients.

Aspirin and statin use may lower the risk of advanced/fatal prostate cancer, possibly by reducing intraprostatic inflammation. To test this hypothesis, we investigated the association of aspirin and statin use with the presence and extent of intraprostatic inflammation, and the abundance of specific immune cell types, in benign prostate tissue from a subset of men from the placebo arm of the Prostate Cancer Prevention Trial. Men were classified as aspirin or statin users if they reported use at baseline or during the 7-year trial. Presence and extent of inflammation were assessed, and markers of specific immune cell types (CD4, CD8, FoxP3, CD68, and c-KIT) were scored, in slides from end-of-study prostate biopsies taken irrespective of clinical indication, per trial protocol. Logistic regression was used to estimate associations between medication use and inflammation measures, adjusted for potential confounders. Of 357 men included, 61% reported aspirin use and 32% reported statin use. Prevalence and extent of inflammation were not associated with medication use. However, aspirin users were more likely to have low FoxP3, a T regulatory cell marker [OR, 5.60; 95% confidence interval (CI), 1.16-27.07], and statin users were more likely to have low CD68, a macrophage marker (OR, 1.63; 95% CI, 0.81-3.27). If confirmed, these results suggest that these medications may alter the immune milieu of the prostate, which could potentially mediate effects of these medications on advanced/fatal prostate cancer risk., (©2020 American Association for Cancer Research.)

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by a newly emergent coronavirus, SARS-CoV-2. The acute phase may be followed by a second phase actually not yet completely understood but probably associated to an autoimmune activation. At the moment is not possible to clearly define an association between immunological findings and pathological symptoms, however, this case report describes the case of a patient who following COVID-19 infection development autoimmune antibodies who persist in time longer than viral phase. Those antibodies can be responsible for the multi pathological clinical picture showed from our patient that, according to EULAR 2019 criteria, could be classified as systemic lupus erythematosus (SLE). SLE is probably one of the possible chronic rheumatologic diseases triggers by COVID-19 and this is the first case of SLE with vasculitis actually described in literature.

Background: Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period., Methods: This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed., Results: Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality., Conclusions: Patients hospitalized during the December holiday period had worse health outcomes, and this could be attributable to the grater CC, especially related to socioeconomic (social deprivation, low income) and behavioral factors (inappropriate diet). The evaluation of all CC components could potentially represent a useful tool for a more rational resource allocation over this time of the year., Competing Interests: The authors have declared that no competing interests exist.

Objective: Coronavirus disease 2019 (COVID-19) related coagulopathy may be the first clinical manifestation even in non-vasculopathic patients and is often associated with worse clinical outcomes., Case Presentation: A 78 years old woman was admitted to the Emergency Unit with respiratory symptoms, confusion and cyanosis at the extremity, in particular at the nose area, hands and feet fingers. A nasal swab for COVID-19 was performed, which resulted positive, and so therapy with doxycycline, hydroxychloroquine and antiviral agents was started. At admission, the patient was hemodynamically unstable requiring circulatory support with liquids and norepinephrine; laboratory tests showed disseminated intravascular coagulation (DIC). During hospitalization, the clinical condition worsened and the cyanosis of the nose, fingers, and toes rapidly increased and became dried gangrene in three days. Subsequently, the neurological state deteriorated into a coma and the patient died., Discussion: In severe cases, COVID-19 could be complicated by acute respiratory disease syndrome, septic shock, and multi-organ failure. This case report shows the quick development of dried gangrene in a non-vasculopathic patient, as a consequence of COVID-19's coagulopathy and DIC., Conclusions: In our patient, COVID-19 related coagulopathy was associated with poor prognosis.

The association between Helicobacter-pylori-induced inflammation and gastric adenocarcinoma is well documented and it has been suggested that the pro-mitotic and apoptotic effect of Cyclooxygenase-2 and Osteopontin on the epithelial cells of the gastric mucosa may have a role in carcinogenesis of the gastric mucosa. The aim of this study was to determine the expression of Cyclooxygenase-2 and Osteopontin in normal gastric mucosa, mucosa with gastritis and gastric mucosa with intestinal metaplasia, in relation to Helicobacter-pylori infection and grade of inflammation. Immunohistochemistry was performed on 108 gastric biopsies in order to detect Cyclooxygenase-2 and Osteopontin expression. The intensity and percentage of staining were evaluated using the H-Score, and its association with grade of inflammation, Helicobacter pylori infection and intestinal metaplasia was determined. Expression of Cyclooxygenase-2 and Osteopontin was higher in gastric biopsies (values shown respectively) with Helicobacter-pylori infection (179.9/142.3), intestinal metaplasia (208.8/179.3) or higher grades of inflammation (190/135.7) in comparison to normal gastric mucosa (100.7/80) or mild grade of inflammation (128.4/128.4), (p<0.05).There is an overexpression of Cyclooxygenase-2 and Osteopontin in gastric mucosa with H. pylori infection, intestinal metaplasia and high grades of inflammation, suggesting a constant up-regulation of protein expression in response to the inflammatory process generated by a Helicobacter-pylori infection, leading to the development of intestinal metaplasia., (Copyright © 2019 Sociedad Española de Anatomía Patológica. Publicado por Elsevier España, S.L.U. All rights reserved.)

Severe helminth infections are negatively associated to allergic diseases like asthma; therefore, the immunomodulatory properties of parasite-derived components have been analyzed, raising the possibility of their use as anti-inflammatory molecules. We evaluated the immunomodulatory properties of Ascaris lumbricoides recombinant cysteine protease inhibitor (rAl-CPI) in a mouse model of allergic airway inflammation induced by the house dust mite (HDM) Blomia tropicalis and its effects on human monocyte-derived dendritic cells (HmoDCs). The B. tropicalis sensitized/challenged mice developed extensive cellular airway inflammatory response, which was significantly reduced upon treatment with rAl-CPI prior to B. tropicalis sensitization, affecting particularly the perivascular/peribronchial infiltrate cells, eosinophils/neutrophils, and goblet cells. A significant decrease of Th2 cytokines, total, and specific IgE antibodies was observed in rAl-CPI treated mice. The antibody response was biased to IgG, mainly IgG2a. Administration of rAl-CPI-alone and rAl-CPI before mite sensitization were associated with a significant increase of regulatory T cells (Tregs) in spleen and elevated IL-10 levels in BAL and splenocytes culture supernatants, which was partially affected by anti-IL10 receptor use. In vitro , rAl-CPI showed a modulatory effect on HmoDCs, lowering the expression of HLA-DR, CD83, and CD86, while inducing IL-10 and IL-6 production. This suggests an inhibition of HmoDC maturation and a possible link with the inhibition of the allergic response observed in the murine model., (Copyright © 2019 Coronado, Zakzuk, Regino, Ahumada, Benedetti, Angelina, Palomares and Caraballo.)

Background: A clinically meaningful impairment of bone mass secondary to malabsorption is frequent in untreated celiac disease. In adult patients, a rigorous gluten-free diet (GFD) significantly improves, but does not always normalize, bone mineral density (BMD). The reason for this marginal response is unclear. Accordingly, we evaluated the role of both local and systemic factors for bone loss in celiac patients on long-term GFD., Study: In a prospective cohort, 22 patients with low lumbar and/or femoral BMD and 22 with normal BMD underwent bone and mineral metabolism evaluation: we tested calcium, phosphate, parathyroid hormone, and vitamin D; telopeptide of type I collagen, a bone resorption index; propeptide of type I procollagen, a bone neoformation index; receptor antagonist of NF-kB ligand, an osteoclast-stimulating factor; osteoprotegerin (OPG), a decoy receptor for RANKL. Sunlight exposure and physical exercise were measured., Results: Patients with bone loss showed prevalently osteopenia, severe osteoporosis was rare. In comparison with normal BMD patients, they showed higher serum OPG, telopeptide, and lower serum propeptide, suggesting an increased bone turnover. Lumbar T-score was negatively correlated with OPG, telopeptide and RANKL and positively with propeptide. Propeptide was negatively correlated with OPG and telopeptide. OPG was positively correlated with telopeptide., Conclusions: The persistent activation of inflammation should be considered the main pathophysiological mechanism for bone defect in celiac disease patients with bone loss on long-term GFD. High levels of OPG, an attempt at protective mechanism, and low levels of propeptide of type I procollagen, reflecting an insufficient matrix production, characterize this subgroup of patients.

Dietary patterns play key roles in health promotion and in preserving the environment. A growing number of studies show the importance of individual factors on food consumption choices, such as socio-economic status, lifestyle variables and contextual and social factors that characterize the geographical area in which individuals reside. The Mediterranean Diet is a sustainable diet that respects the environment, thus reducing per capita emissions from food production in respect to less sustainable diet. The aim of this paper is to determine the Italians' prevailing food patterns using a composite indicator and to identify which factors determine a higher adherence to the Mediterranean Diet in Italy. By using 15 waves of the ISTAT "Aspect of Daily Life" survey, we constructed an original data set and referred to the multilevel approach which enabled us to distinguish between temporal and cross-sectional effects thus providing valuable insights to policy makers and stakeholders in order to promote the Mediterranean Diet and reap environmental and public health. The results show that education plays an important role in determining food consumption behavior while the tendency to practice sports on a regular basis and to have breakfast and lunch at home positively influence people's adherence to this diet., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Atypical chemokine receptors have recently emerged as important molecular players in health and diseases; they affect chemokine availability and function and impact a multitude of pathophysiological events, including the tumorigenesis process. This family of atypical receptors comprises five members: ACKR1/DARC, ACKR2/D6, ACKR3/CXCR7, ACKR4/CCRL1, and ACKR5/CCRL2. This work evaluated the differential expression of these receptors in prostate cancer using quantitative PCR. Further evaluation of CCRL2 at the protein level confirmed its overexpression in a metastatic cell line and in malignant prostatic tissues from patients. CCRL2, a presumed member of the atypical chemokine receptor family, plays a key role in lung dendritic cell trafficking to peripheral lymph nodes. Recent studies have reported the expression of CCRL2 in different human cancer cell lines and tissues. However, its function and expression in prostate cancer has not been previously addressed.

Identification of genes specifically deregulated in prostate adenocarcinoma may lead to discovery of new oncogenes/tumour suppressors with clinical relevance for diagnosis, prognosis and/or therapy. CXXC5 is a gene encoding a retinoid-inducible nuclear factor, whose overexpression in breast tumours, metastatic malignant melanomas and papillary thyroid carcinoma has been recently reported. We previously found differential expression of CXXC5 transcripts in metastatic prostate cancer cell lines of both rat and human origin. However, knowledge on the expression of this gene in benign or malignant human prostate tissue is lacking. The aim of this study was to determine the mRNA and protein expression pattern of CXXC5 in human benign prostate tissue, proliferative inflammatory atrophy, high-grade prostatic intra-epithelial neoplasia and prostate cancer, using qPCR, chromogenic in situ hybridization and immunohistochemistry. Our results showed that protein levels determined by immunohistochemistry were in agreement with transcript levels observed by chromogenic in situ hybridization. CXXC5 mRNA and protein expressions were significantly higher in prostate cancer, high-grade prostatic intra-epithelial neoplasia, and proliferative inflammatory atrophy, compared to benign prostate tissue. Significantly, within the same tissue specimens, CXXC5 staining was stronger in malignant acini than in matched adjacent, benign acini; immunostaining for this protein was mainly localized to the nucleus of benign epithelial cells and both the nucleus and cytoplasm of malignant epithelial cells. Our findings suggest that CXXC5 may play a role in the process of prostate carcinogenesis. Additional studies are required to determine the biological and clinical significance of CXXC5 in prostate cancer development and/or progression., (© 2017 The Authors. International Journal of Experimental Pathology © 2017 International Journal of Experimental Pathology.)

Gene expression noise is not only the mere consequence of stochasticity, but also a signal that reflects the upstream physical dynamics of the cognate molecular machinery. Soil bacteria facing recalcitrant pollutants exploit noise of catabolic promoters to deploy beneficial phenotypes such as metabolic bet-hedging and/or division of biochemical labor. Although the role of upstream promoter-regulator interplay in the origin of this noise is little understood, its specifications are probably ciphered in flow cytometry data patterns. We studied Pm promoter activity of the environmental bacterium Pseudomonas putida and its cognate regulator XylS by following expression of Pm-gfp fusions in single cells. Using mathematical modeling and computational simulations, we determined the kinetic properties of the system and used them as a baseline code to interpret promoter activity in terms of upstream regulator dynamics. Transcriptional noise was predicted to depend on the intracellular physical distance between regulator source (where XylS is produced) and the target promoter. Experiments with engineered bacteria in which this distance is minimized or enlarged confirmed the predicted effects of source/target proximity on noise patterns. This approach allowed deconvolution of cytometry data into mechanistic information on gene expression flow. It also provided a basis for selecting programmable noise levels in synthetic regulatory circuits.

The possible origin of proliferative inflammatory atrophy in the regenerative proliferation of prostate epithelial cells in response to injury caused by inflammation, and their relation to prostate adenocarcinoma have not been defined. Inflammation and focal atrophy are common pathological findings in prostate biopsies, currently not routinely included in surgical pathology reports. The objective of the study was to determine the correlation between inflammation and focal atrophy with prostate adenocarcinoma. Prostate needle biopsies from 203 patients with clinical parameters suspicious for malignancy were evaluated for the presence and extent of chronic inflammation, type and grade of focal atrophy, high-grade intraepithelial neoplasia, and adenocarcinoma. Relations among them and with age were also analyzed. χ(2) tests and binary logistic regression were used to estimate associations. Chronic inflammation was observed in 77.3% of the biopsies, significantly associated to adenocarcinoma (P = .031). Moderate/severe inflammation in at least 1 biopsy core increased the risk of prostate adenocarcinoma (odds ratio, 2.94; 95% confidence interval, 1.27-6.8), whereas glandular localization of inflammation decreased the risk. Focal atrophy was present in 72.9% of the biopsies, proliferative inflammatory atrophy was the most common type, and its grade was significantly associated to inflammation (P < .0001) and inflammation intensity (P = .003). An association between prostate adenocarcinoma and inflammation was found, with higher odds in presence of moderate/severe inflammation in at least 1 biopsy core. Increasing grades of proliferative inflammatory atrophy were associated to high levels of inflammation, supporting its previously proposed inflammatory nature., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Nutritional abnormalities and physical inactivity are risk factors of increased morbidity and mortality in patients with ESRD. Identify and define malnutrition, in particular protein-energy depletion (PEW), is an important task in the management of renal patients. The aim of this multicenter observational study was to implement the assessment of nutritional status and functional capacity in patients on peritoneal dialysis, including tests and validated methods which are relatively easy to apply in daily clinical practice. The study includes all the 133 prevalent patients (80 m, 53 f, age 65 14 years), in peritoneal dialysis treatment (vintage 26 19 months) in 9 centers in Tuscany. We performed anthropometry, bioimpedance (BIA), clinical biochemistry, evaluation of habitual physical activity (RAPA tests) and performance (Sit-To-Stand test), appetite-evaluation questionnaire, and indices including the Malnutrition Inflammation Score (MIS), Geriatric Nutrition Risk Index (GNRI), Charlson comorbidity index, Barthel and Karnowsky index. The latter showed a condition of dependence in 7.2% and 19.7% of cases, respectively. Poor appetite was recorded in 48.2%. The majority of patients fell within the overweight / obesity range (51%) with waist circumference values associated with increased cardiovascular risk in 51% of males and 60% of females. At the BIA analysis, a BCMI <8 kg/m2 was detected in 39% of patients; an estimated protein intake <1.0 g / kg/d was found in 59% of cases; 34% of patients had serum albumin <3.5 g / dl; control of acidosis was good (bicarbonate 25.4 3.8 mM) but hyperphosphatemia was present in 64.6% of patients. A condition of sedentary or light physical activity was reported by 65.1% of patients, vigorous activity only by 11.9%. The 86.5% of patients able to perform the Sit-to-stand test reported a lower than the reference values for age and sex. A diagnosis of PEW was possible in 8% of our series, while a MIS score> 11, indicative of PEW, took place in 12.7% of cases. The values of the MIS correlated directly with age and the degree of comorbidity and inversely with the sit-to-stand test, RAPA tests and appetite level. The data in this study show that single tests indicative of malnutrition disorders are frequent to be found in our series of peritoneal dialysis patients. However, a diagnosis of PEW is quite infrequent. A large percentage of patients are overweight with increased abdominal adiposity, and reduced cell mass and protein intake below recommended levels; the level of habitual physical activity is low, and the level of physical capability is scarce. Therefore it is conceivable a nutritional counseling intervention to increase the intake of proteins, limiting the phosphorus and (when indicated) energy intake and to stimulating spontaneous physical activity or arranging assisted programs for functional rehabilitation. Close monitoring of the nutritional status and implementation of programs of adapted physical activity should have a prominent role in the clinical management of patients on peritoneal dialysis.

Transcriptional noise is a necessary consequence of the molecular events that drive gene expression in prokaryotes. However, some environmental microorganisms that inhabit polluted sites, for example, the m-xylene degrading soil bacterium Pseudomonas putida mt-2 seem to have co-opted evolutionarily such a noise for deploying a metabolic diversification strategy that allows a cautious exploration of new chemical landscapes. We have examined this phenomenon under the light of deterministic and stochastic models for activation of the main promoter of the master m-xylene responsive promoter of the system (Pu) by its cognate transcriptional factor (XylR). These analyses consider the role of co-factors for Pu activation and determinants of xylR mRNA translation. The model traces the onset and eventual disappearance of the bimodal distribution of Pu activity along time to the growth-phase dependent abundance of XylR itself, that is, very low in exponentially growing cells and high in stationary. This tenet was validated by examining the behaviour of a Pu-GFP fusion in a P. putida strain in which xylR expression was engineered under the control of an IPTG-inducible system. This work shows how a relatively simple regulatory scenario (for example, growth-phase dependent expression of a limiting transcription factor) originates a regime of phenotypic diversity likely to be advantageous in competitive environmental settings.

Engineering of robust microbial cell factories requires the use of dedicated genetic tools somewhat different from those traditionally used for laboratory-adapted microorganisms. We have edited and formatted the ChnR/P chnB regulatory node of Acinetobacter johnsonii to ease the targeted engineering of ectopic gene expression in Gram-negative bacteria. The proposed compositional standard was thoroughly verified with a monomeric and superfolder green fluorescent protein (msf•GFP) in Escherichia coli. The expression data presented reflect a tightly controlled transcription initiation signal in response to cyclohexanone. Data in this article are related to the research paper "Genetic programming of catalytic Pseudomonas putida biofilms for boosting biodegradation of haloalkanes" [1].

Background: Fibromodulin is a small leucine-rich proteoglycan important for extracellular matrix organization and essential for tissue repair in multiple organs. The main function of this proteoglycan is the regulation of collagen fibrillogenesis; however, more recently described roles for fibromodulin have expanded to include regulation of angiogenesis, reprogramming of human fibroblasts into pluripotent cells, modulation of TGF-β activity, inflammatory processes and association with metastatic phenotypes. Additionally, fibromodulin has been identified as a novel tumor-associated antigen in leukemia, lymphoma, and leiomyoma. Knowledge about its expression in the prostate is limited., Methods: Fibromodulin expression was analyzed in two different malignant and one non-tumorigenic prostatic cell lines in culture, and in benign and malignant human prostate tissue. Expression was analyzed by real time PCR, immunocytochemistry, and immunohistochemistry. DNA sequencing was performed on a PCR fragment amplified with primers specific for the FMOD gene from cDNA obtained from the cultured cell lines., Results: Both immunostaining and real time PCR analysis of cell lines indicated that fibromodulin was differentially expressed in the cancerous cell lines compared to the non-tumorigenic cell line. Likewise, cancerous tissue expressed significantly higher levels of intracellular fibromodulin compared to matched, benign tissue from the same patients, as well as compared to tissue from patients with only benign disease., Conclusions: The expression of fibromodulin was higher in prostatic cancer cells (cell-lines and human tissue) than in normal/benign prostatic cells. Additional studies are required to determine the biological and clinical significance and whether this proteoglycan has a role in carcinogenesis of the prostate or in prostate cancer related inflammatory processes.

Bacterial biofilms outperform planktonic counterparts in whole-cell biocatalysis. The transition between planktonic and biofilm lifestyles of the platform strain Pseudomonas putida KT2440 is ruled by a regulatory network controlling the levels of the trigger signal cyclic di-GMP (c-di-GMP). This circumstance was exploited for designing a genetic device that over-runs the synthesis or degradation of c-di-GMP--thus making P. putida to form biofilms at user's will. For this purpose, the transcription of either yedQ (diguanylate cyclase) or yhjH (c-di-GMP phoshodiesterase) from Escherichia coli was artificially placed under the tight control of a cyclohexanone-responsive expression system. The resulting strain was subsequently endowed with a synthetic operon and tested for 1-chlorobutane biodegradation. Upon addition of cyclohexanone to the culture medium, the thereby designed P. putida cells formed biofilms displaying high dehalogenase activity. These results show that the morphologies and physical forms of whole-cell biocatalysts can be genetically programmed while purposely designing their biochemical activity., (Copyright © 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.)

The soil bacterium Pseudomonas putida is increasingly attracting considerable interest as a platform for advanced metabolic engineering through synthetic biology approaches. However, genomic context, gene copy number, and transcription/translation interplay often introduce considerable uncertainty to the design of reliable genetic constructs. In this work, we have established a standardized heterologous expression device in which the promoter strength is the only variable; the remaining parameters of the flow have stable default values. To this end, we tailored a mini-Tn7 delivery transposon vector that inserts the constructs in a single genomic locus of P. putida's chromosome. This was then merged with a promoter insertion site, an unvarying translational coupler, and a downstream location for placing the gene(s) of interest under fixed assembly rules. This arrangement was exploited to benchmark a collection of synthetic promoters with low transcriptional noise in this bacterial host. Growth experiments and flow cytometry with single-copy promoter-GFP constructs revealed a robust, constitutive behavior of these promoters, whose strengths and properties could be faithfully compared. This standardized expression device significantly extends the repertoire of tools available for reliable metabolic engineering and other genetic enhancements of P. putida.

In developed countries, typhoid fever is often associated with persons who travel to endemic areas or immigrate from them. Typhoid fever is a systemic infection caused by Salmonella enterica serovar Typhi. Because of the emergence of antimicrobial resistance to standard first-line drugs, fluoroquinolones are the drugs of choice. Resistance to ciprofloxacin by this Salmonella serovar represents an emerging public health issue. Two S. enterica ser. Typhi strains resistant to ciprofloxacin (CIP) were reported to the Italian surveillance system for foodborne and waterborne diseases (EnterNet-Italia) in 2013. The strains were isolated from two Italian tourists upon their arrival from India. A retrospective analysis of 17 other S. enterica ser. Typhi strains isolated in Italy during 2011-2013 was performed to determine their resistance to CIP. For this purpose, we assayed for susceptibility to antimicrobial agents and conducted PCR and nucleotide sequence analyses. Moreover, all strains were typed using pulsed-field gel electrophoresis to evaluate possible clonal relationships. Sixty-eight percent of the S. enterica ser. Typhi strains were resistant to CIP (MICs, 0.125-16 mg/L), and all isolates were negative for determinants of plasmid-mediated quinolone resistance. Analysis of sequences encoding DNA gyrase and topoisomerase IV subunits revealed mutations in gyrA, gyrB, and parC. Thirteen different clonal groups were detected, and the two CIP-resistant strains isolated from the individuals who visited India exhibited the same PFGE pattern. Because of these findings, the emergence of CIP-resistant S. enterica ser. Typhi isolates in Italy deserves attention, and monitoring antibiotic susceptibility is important for efficiently managing cases of typhoid fever.

The scientific and technical ambition of contemporary synthetic biology is the engineering of biological objects with a degree of predictability comparable to those made through electric and industrial manufacturing. To this end, biological parts with given specifications are sequence-edited, standardized, and combined into devices, which are assembled into complete systems. This goal, however, faces the customary context dependency of biological ingredients and their amenability to mutation. Biological orthogonality (i.e., the ability to run a function in a fashion minimally influenced by the host) is thus a desirable trait in any deeply engineered construct. Promiscuous conjugative plasmids found in environmental bacteria have evolved precisely to autonomously deploy their encoded activities in a variety of hosts, and thus they become excellent sources of basic building blocks for genetic and metabolic circuits. In this article we review a number of such reusable functions that originated in environmental plasmids and keep their properties and functional parameters in a variety of hosts. The properties encoded in the corresponding sequences include inter alia origins of replication, DNA transfer machineries, toxin-antitoxin systems, antibiotic selection markers, site-specific recombinases, effector-dependent transcriptional regulators (with their cognate promoters), and metabolic genes and operons. Several of these sequences have been standardized as BioBricks and/or as components of the SEVA (Standard European Vector Architecture) collection. Such formatting facilitates their physical composability, which is aimed at designing and deploying complex genetic constructs with new-to-nature properties.

Bacteria display considerable cell-to-cell heterogeneity in a number of genetic and physiological traits. Stochastic differences in regulatory patterns (e.g. at the transcriptional level) propagate into the metabolic and physiological status of otherwise isogenic cells, which ultimately results in appearance of sub-populations within the community. As new technologies emerge and because novel single cell strategies are constantly being refined, our knowledge on microbial individuality is in burgeoning and constant expansion. These approaches encompass not only molecular biology tools (e.g. fluorescent-protein based reporters) but also a suite of sophisticated, non-invasive technologies to gain insight into the metabolic state of individual cells. Defining the role of individual heterogeneities is thus instrumental for the population-level understanding of macroscopic processes in both environmental and industrial set-ups. The present article reviews the state-of-the-art methodologies for the investigation of single bacteria at both the genetic and metabolic level, and places the application of currently available tools in the context of microbial ecology and environmental microbiology. As a case example, we examine the stochastic and multi-stable behaviour of the TOL-encoded pathway of Pseudomonas putida mt-2 for the biodegradation of aromatic compounds. Bet-hedging strategies and division of labour are considered as factors pushing forward the evolution of environmental microorganisms., (© 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.)

Reporter genes are widely used to quantify promoter activity, which controls production of mRNA through the interplay with RNA polymerases and transcription factors. Some of such reporters have either diffuse (lux) or focused (GFP) optical outputs that allow description of transcriptional activity in populations and in single cells. This chapter discusses the use of a dual reporter system GFP-luxCDABE that is placed in broad-host-range plasmids having origins of replication from RK2 and pBBR1. The value of this system is shown in Pseudomonas putida by characterizing the activity of the Pb promoter, which drives an operon for benzoate biodegradation in this bacterium. To this end we compare in the same cells bioluminescence as the output signal of the whole population and single cell-bound fluorescence caused by GFP expression and revealed by flow cytometry assays.

Background: Information about the biological properties of Blomia tropicalis allergens is scarce. It is predicted that Blo t 12, an allergen with two described isoforms, contains a chitin-binding domain, similar to that found in peritrophins. Th2 adjuvant properties have been described for chitin. Therefore, it is feasible that binding to this carbohydrate influences its allergenicity. We aimed to evaluate the chitin-binding activity of Blo t 12 isoallergens and its effect on airway inflammation and antibody responses in a murine model of allergen sensitization., Methods: Chitin-binding assays were conducted with the recombinant isoallergens Blo t 12.0101 and Blo t 12.0102. BALB/c mice were sensitized via i.p. with any of the two isoforms (alone, with chitin or alum) and then challenged intranasally. Methacholine-induced bronchial hyperreactivity was tested by whole-body plethysmography and lung sections were stained with hematoxylin and eosin and periodic-acid Schiff. Total IgE and allergen-specific IgE, IgG1 and IgG2 levels were measured by ELISA., Results: The two isoforms bound chitin, but Blo t 12.0101 showed a stronger binding capacity. Both isoforms induced total and allergen-specific IgE, airway hyperreactivity, bronchial inflammation and mucus secretion without any adjuvant; however, when administered with chitin, Blo t 12.0101 induced higher total IgE levels. The IgG1/IgG2a ratio was significantly higher in mice immunized with Blo t 12.0101 than those immunized with Blo t 12.0102. As peritrophins, Blo t 12 was detected in mite feces., Conclusions: Blo t 12 isoforms are chitin-binding proteins that induce airway inflammation and bronchial hyperreactivity. However, for Blo t 12.0101, chitin reinforces its effects on total IgE production.

During 2005-2006, Salmonella enterica serotype Infantis strains isolated from human and non-human sources and resistant to ampicillin (A), chloramphenicol (C), streptomycin (S), sulphonamide (Su), tetracycline (T), kanamycin (K) and trimethoprim/sulfamethoxazole (Sxt) emerged in Italy. The aim of this study was to analyse the molecular basis of antibiotic resistance and to evaluate the clonal origin of multiresistant S. Infantis strains isolated from different sources. Seventy S. Infantis strains, susceptible or resistant to antimicrobial drugs, were chosen for this study. Polymerase chain reaction (PCR) and conjugation experiments were performed to identify and localise the resistance genes in multidrug-resistant strains. PCR-based replicon typing was carried out for characterisation of conjugative plasmids. All strains were tested by pulsed-field gel electrophoresis (PFGE) according to the PulseNet protocol, and cluster analysis was performed using BioNumerics software. Strains with resistance (R)-type ACSSuTKSxt harboured bla(TEM-1), strA-B, sul2, tet(B), catA1 and aphA-1 resistance genes as well as a 2.2-kb class 1 integron containing folA, catB3, aadA4 and sul1 gene cassettes. A unique plasmid, belonging to the HI1 incompatibility group, harboured all the resistance genes. Cluster analysis showed that all ACSSuTKSxt-resistant strains belonged to a large cluster (A) with >90% genetic similarity. The presence of a plasmid harbouring all the resistance gene cassettes as well as molecular typing by PFGE demonstrated the circulation of a cluster of S. Infantis R-type ACSSuTKSxt during 2005-2006 in Italy. The presence of a plasmid conferring multidrug resistance could have facilitated the spread of a group of similar isolates through a variety of sources., (Copyright © 2011 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.)

Several studies suggest that the 24 hour ambulatory blood pressure monitoring (ABPM) predicts left ventricular hypertrophy more accurately than conventional blood pressure measurement (CBPM) with mercury sphygmomanometer. We estimated the left ventricular mass by M-mode echocardiography in 58 patients on regular haemodialysis treatment during the midweek haemodialysis (HD) interval. ABPM was recorded during the 24 hours preceding the dialysis session and the average of values were compared with the average of the 13 pre HD CBPM recorded by nurses during the month preceding the echocardiography study. The two types of BP measurements correlated significantly with each other, (systolic BP r = 0.62; p < 0.001 and diastolic BP r = 0.74; p < 0.001). The correlation of left ventricular mass with pre-HD systolic BP was stronger (r = 0.54; p < 0.001) than with 24h-systolic BP (r = 0.33; p < 0.01). The overall accuracy of prediction was also similar (68% for pre HD-CBPM; 67% for 24h-ABPM). Measurements of diastolic BP did not correlate significantly with LVM. Our data suggest that 24h-ABPM does not offer any advantage over pre HD-CBPM in predicting left ventricular hypertrophy in HD patients.

Quantitative microfluorometric evaluation indicated that, in Lophius piscatorius, the DNA content of large neurons of a cluster located at the boundary between the medulla oblongata and the spinal cord varied from 4C to more than 5000C. This finding must be considered exceptional for the nervous system of Vertebrates. DNA contents were correlated to both nuclear and animal size. Utilization of AT and GC specific fluorochromes showed that the increase in DNA content is due to differential genome amplification involving GC-rich DNA sequences.

Peculiar dorsal neurons present in the dorsal spinal cord of Trigla lucerna L. and Scorpaena porcus L. were investigated by neuroanatomical and immunohistochemical methods. These neurons were previously defined as commissural cells, but have now been identified as supramedullary neurons. The following fundamental criteria for identifying the supramedullary neurons of Teleosts are proposed: a) dorsomedial location in the spinal cord; b) large size of the soma and axon; c) immunoreactivity to gastrin/CCK-like peptides.

The central nervous system of Lophius piscatorius has a cluster of large neurons located at the boundary between the medulla oblongata and spinal cord. The DNA content of these neurons was evaluated by microfluorimetric methods. Results demonstrated a DNA content ranging from a minimum of 8C in the smaller to over 1000C in the larger neurons of L. piscatorius cluster. These data are exceptional for the nervous system of Vertebrates, and known only for the giant neurons of Mollusca.

This work describes the acid phosphatase activity in supramedullary neurons of Coris julis, analyzed by a cytochemical method. The presence of both acid phosphatase-positive and -negative membrane bound granules indicates that only a part of the numerous electrodense granules in the supramedullary neurons can be interpreted as lysosomes. The great number of lysosomes in these large neurons of young animals is indicative of the rapid turnover of cell structures, which may be correlated with the high rate of synthesis. The electrodense granules showing no acid phosphatase activity are postulated to be vesicles containing gastrin/CCK-like peptide or precursors of this neuromediator.

Some Teleosts belonging to the orders Batrachoidiformes, Lophiiformes, Perciformes and Tetraodontiformes show a cluster of large neurons dorsally located at the boundary between the spinal cord and medulla oblongata. These elements have traditionally been grouped with the supramedullary neurons aligned in the dorso-medial region of the spinal cord of other teleosts (see Marini and Benedetti, in press). However, recent morphological and immunohistochemical studies have suggested that the neurons grouped in a cluster on the spinal cord of Lophius piscatorius may not be of the same nature as the supramedullary neurons aligned within the dorsal gray matter of the spinal cord (Benedetti and Mola, 1988; Mola, 1990). Over the course of these previous investigations, it seemed that the nucleus of the neurons in the cluster showed more abundant chromatin than other neurons in the dorsal spinal cord. This prompted a series of investigations on the nucleus of these neurons.

The ultrastructural study of the supramedullary neurons in Crenilabrus quinquemaculatus shows that these cells are engaged in intense synthetic activity as is testified by the nuclear morphology, the plentiful rough endoplasmic reticulum and polysomes, and finally the remarkably developed Golgi complexes, many of them active. Moreover the cytoplasm of the supramedullary neurons shows numerous membrane-bounded bodies (1,800-4,000 A) containing electron dense material, more or less finely granular. Research is presently being carried out to establish the meaning of these electron dense bodies.

Experimental lead pollution was studied in some organs (foot, mantle and digestive gland) of Viviparus viviparus L. The amount of lead contained after 48h, 96 h and one week of pollution were established using an atomic absorption spectrophotometer. On the basis of physicochemical determination, it turns out that lead is mainly concentrated in the mantle. The biochemical tests (cholesterol, sulpholipids and phospholipids) were aimed at evaluating the lipids involved in the membranes. The histochemical research was carried out chiefly to evaluate the modifications of polysaccharides and proteins. Some hydrolytic enzymes (Na+ and K+ dependent ATPase) and some ooreductive enzymes (NADH+ and NADPH+ dependent diaphorases, D-lactate dehydrogenase, succinate dehydrogenase and glucose-6-P-dehydrogenase) were also tested. The digestive gland is the most severely damaged organ as proved by histomorphological and biochemical analyses.

The distribution of glycogen in the central nervous system of the viviparous teleost Gambusia affinis and of the oviparous teleost Jordanella floridae during development and in the adults, was examined. It emerged that the glycogen pattern in adults of Gambusia and Jordanella is very similar, whereas there are considerable differences during development. These differences were related to the different ways in which development takes place in the two species.

The subject of this work is an analysis of the mitotic activity in the developing spinal cord and rhombencephalon of the oviparous teleost Jordanella floridae and the viviparous teleost Gambusia affinis (Cyprinodontoidei). In Gambusia there is considerable and long lasting mitotic activity that decreases gradually and is still present 20 days after birth. In Jordanella the mitotic activity is concentrated in the early stages of development, it then decreases drastically and practically disappears even before hatching and reappears 20 days later. These differences are probably due to the variations in speed and pattern of development in the two teleosts. As regard the localization of mitoses, it emerged that migration towards the lumen may be prevented by physiological conditions related to normal development. It emerged moreover, that migration towards the lumen is not a generalised phenomenon in development of the central nervous system since it is related, in the spinal cord of teleosts at least, to the modality and speed of embryo development.

The supramedullary neurons of the marine teleost Coris julis (L.) were surveyed for neuropeptide-like immunoreactivity using antisera against 12 peptides. These neurons exhibit positive immunoreactivity to CCK-8, CCK-39 and gastrin(18-34). The presence of gastrin/CCK-like peptides in the supramedullary neurons is discussed.