Anterior Segment Optical Coherence Tomography in Uveitis-Glaucoma-Hyphema Syndrome.

PURPOSE: Uveitis-Glaucoma-Hyphema (UGH) syndrome results from contact between the intraocular lens (IOL) and the iris or ciliary body, leading to uveal structure erosion and blood-aqueous barrier breakdown. Treatment involves various drugs, with IOL removal often being necessary. Diagnosis relies on clinical signs, but imaging techniques like ultrasound biomicroscopy (UBM) or anterior segment optical coherence tomography (AS-OCT) are crucial. AS-OCT accurately depicts IOL position and potential contact, emerging as a primary alternative to UBM in the diagnosis. Our study aimed to correlate AS-OCT findings with clinically detectable iris atrophy in pseudophakic patients with IOL-iris chafing and UGH syndrome. METHODS: The study retrospectively analyzed patients diagnosed with UGH syndrome presenting at the Ocular Immunology Unit of Reggio Emilia, Italy, from January 2019 to August 2023. Patients' data were collected. Ophthalmological exams and imaging were performed. The peephole sign in AS-OCT images was evaluated. Statistical analyses were conducted, with a significance level of p ≤ 0.05. RESULTS: The study reviewed 22 eyes of 22 patients with UGH syndrome. Four eyes were excluded, leaving 18 patients (8 females, 10 males). Common misdiagnoses included idiopathic anterior uveitis (55.5%) and herpetic anterior uveitis (16.7%). All patients had iris transillumination defects, mostly focal (77.8%). AS-OCT revealed IOL chafing in all the eyes, with peephole sign correlation. More peephole signs occurred with IOL in the sulcus (p-value = 0.08). CONCLUSION: The study recommends AS-OCT for UGH syndrome confirmation and UBM when IOL-iris chafing is not observed on AS-OCT scans.

Ecology explains anhydrobiotic performance across tardigrades, but the shared evolutionary history matters more.

Desiccation stress is lethal to most animals. However, some microinvertebrate groups have evolved coping strategies, such as the ability to undergo anhydrobiosis (i.e. survival despite the loss of almost all body water). Tardigrades are one such group, where the molecular mechanisms of anhydrobiosis have been more thoroughly studied. Despite the ecological, evolutionary and biotechnological importance of anhydrobiosis, little is known about its inter- and intra-specific variability nor its relationship with natural habitat conditions or phylogenetic history. We developed a new index-anhydrobiotic recovery index (ARI)-to evaluate the anhydrobiotic performance of tardigrade populations from the family Macrobiotidae. Moreover, we compared the explanatory role of habitat humidity and phylogenetic history on this trait using a variance partitioning approach. We found that ARI is correlated with both microhabitat humidity and yearly rainfall, but it is mostly driven by phylogenetic niche conservatism (i.e. a high portion of ARI variation is explained by phylogeny alone). Finally, we showed that anhydrobiotic performance is highly variable, even between closely related species, and that their response to local ecological conditions is tightly linked to their phylogenetic history. This study not only presents key insights into an emerging model system, but also provides a new methodological approach for wider scale studies of the ecological and evolutionary implications of anhydrobiosis.

Effect of an Escherichia coli F4/F18 bivalent oral live vaccine on gut health and performance of healthy weaned pigs.

Oral live vaccines stimulate host immunity, but they could also affect intestinal mucosa development and gut microbiota of piglets during the postweaning. The aim of this study was to determine the effect of an oral vaccine against Escherichia coli F4 and F18 (Coliprotec F4/F18®), on gut functionality and integrity, growth performance and health status of postweaning piglets. A total of 96 weaned piglets (23.30 ±â€¯1.85 days of age; 7334 ±â€¯1039 g BW) were divided into two groups (16 replicates/group; three piglets/replicate) as follows: (1) Control (CO), fed a standard diet (prestarter up to 14 days, then starter feed); (2) Treated (TRT): as CO but vaccinated with Coliprotec F4/F18® at weaning (day 0). Piglets were weighed at day 0 and weekly until day 35. Individual faecal score was recorded daily. Piglets were sacrificed at days 10 (1/3 of total) and 35 (2/3). Samples of jejunum mucosa and of cecum content were collected for morphometric, immunohistochemistry analysis and for microbiota profile analysis, respectively. Data were fitted using a linear model including treatment, class of starting BW as fixed factors and litter as random factor. From days 0 to 7, piglets from the TRT group tended to have a higher average daily gain (+22.6%, P = 0.08) and average daily feed intake compared to the CO group (+13.2%, P = 0.022). Gain to feed ratio was lower in the TRT group from days 14 to 35 (-6.6%, P = 0.011). From days 7 to 14, the TRT group had a higher diarrhoea index (-199%, P < 0.001). Crypt depth was higher in the CO group (+10.9%, P = 0.04) at day 10, but not at day 35. Jejunal expression of Claudin-4 (probability of having a score = 3) was higher in the TRT group at day 10 (CO = 1.50% vs TRT = 2.69%, P < 0.0001) and day 35 (CO = 1.29% vs TRT = 1.92%, P = 0.012). Oral vaccine affected beta diversity at day 10 (P = 0.040; R2 = 0.05) and increased the abundance of specific taxa and genera in the cecum at day 10, including Prevotella (lg2FC = 23.2, FDR < 0.001). The results showed how an Escherichia coli-based vaccine supplied to weaned pigs can promote gut health by controlling symptoms of the postweaning perturbation in the first 2 weeks postweaning. In addition, the vaccine strains showed a probiotic-like effect by modulating gut microbiota favouring the establishment of beneficial bacteria, and by promoting gut barrier integrity.

Use of a proline-specific endopeptidase to reintroduce gluten in patients with non-coeliac gluten sensitivity: A randomized trial.

BACKGROUND: A gluten-free diet (GFD) is the main therapy for non-coeliac gluten sensitivity (NCGS). However, the availability of novel enzymes with the ability to digest gluten could represent a therapeutic opportunity for NCGS patients to avoid a GFD. AIMS: To evaluate the controlled reintroduction of gluten with or without the endopeptidase P1016 in NCGS patients. METHODS: This is a randomized, double-blind, placebo-controlled monocentric study, Registered under ClinicalTrials.gov Identifier no. NCT01864993. Gluten was reintroduced incrementally over a 3-week period under nutritional control. NCGS patients were randomized into two groups and administered P1016 or placebo during gluten reintroduction. We evaluated symptoms (visual analogue scale, VAS), quality of life (SF-36) and mental health symptoms (SCL-90) on a weekly basis. RESULTS: We enrolled a total 23 patients who were allocated to a placebo group (n = 11, age 38.4 ± 2.9) or an intervention group (n = 12, age 39.5 ± 3.1). No effect of P1016 on symptoms was found. During gluten reintroduction, patients reported a significant increase in abdominal pain and a worsening of stool consistency. Furthermore, no differences were found between the groups regarding SCL-90 and SF-36 scores. CONCLUSIONS: Our results demonstrate a lack of effect of P1016 in the management of NCGS patients and the possible reintroduction of gluten.

Quality of endoscopic screening for colorectal cancer in Italy: A national survey.

BACKGROUND: Colorectal cancer (CRC) is a major healthcare problem all over the world and screening is effective in reducing mortality and increasing survival. Since colonoscopy has a central role in faecal immunochemical test (FIT)-based CRC screening and surveillance, consistent quality measures are essential to ensure quality and outcomes. Nevertheless, screening modalities in clinical practice may differ according to the centers experience and the local availability of instrumentation and devices. AIMS: to assess the quality of endoscopic screening for CRC and adherence to international guidelines across Gastroenterology Departments in Italy. METHODS: All members of the Italian Society of Gastroenterology (SIGE) were invited to answer a web-based survey. RESULTS: Data from 64 hospitals from 17 Italian regions were analyzed. 32/64 (50.0%) were from northern, 12/64 (18.75%) from central and 20/64 (31.25%) from southern Italy. Each center is equipped with a median of 5.0 (3.5-7.0) endoscopists involved in CRC screening, 71.4% of which are gastroenterologists. After a positive FIT, most centers (93.8%) schedule a colonoscopy within 3 months. High-definition video endoscopy is routinely performed in 68.8% and chromoendoscopy in 53.1% of centers. Withdrawal time is ≥6 min in 79.9% and cecal intubation rate is ≥90% in 94.4% of departments. Finally, in 92.7% of centers adenoma detection rate (ADR) overcome the minimum standard of 25%. Analyzing the data by regional areas, a significant higher number of median endoscopic examinations/year (6500 vs 4000 and 3000, respectively, p = 0.024) and of endoscopists per center (6.5 vs 5.0 and 3.5, respectively, p < 0.001) has been registered in the northern compared to central-southern centers. CONCLUSIONS: Data from this survey show adequacy and good quality of endoscopic screening for CRC in Italy, highlighting, at the same time, relevant deficiencies and a discrepancy in procedural attitudes between the different centers. These findings call for a urgent action to overcome the shortcomings, refine and homogenize the behaviour of all screening centers in the national territory and improve the outcomes.

CDK12 promotes tumorigenesis but induces vulnerability to therapies inhibiting folate one-carbon metabolism in breast cancer.

Cyclin-dependent kinase 12 (CDK12) overexpression is implicated in breast cancer, but whether it has a primary or only a cooperative tumorigenic role is unclear. Here, we show that transgenic CDK12 overexpression in the mouse mammary gland per se is sufficient to drive the emergence of multiple and multifocal tumors, while, in cooperation with known oncogenes, it promotes earlier tumor onset and metastasis. Integrative transcriptomic, metabolomic and functional data reveal that hyperactivation of the serine-glycine-one-carbon network is a metabolic hallmark inherent to CDK12-induced tumorigenesis. Consistently, in retrospective patient cohort studies and in patient-derived xenografts, CDK12-overexpressing breast tumors show positive response to methotrexate-based chemotherapy targeting CDK12-induced metabolic alterations, while being intrinsically refractory to other types of chemotherapy. In a retrospective analysis of hormone receptor-negative and lymph node-positive breast cancer patients randomized in an adjuvant phase III trial to 1-year low-dose metronomic methotrexate-based chemotherapy or no maintenance chemotherapy, a high CDK12 status predicts a dramatic reduction in distant metastasis rate in the chemotherapy-treated vs. not-treated arm. Thus, by coupling tumor progression with metabolic reprogramming, CDK12 creates an actionable vulnerability for breast cancer therapy and might represent a suitable companion biomarker for targeted antimetabolite therapies in human breast cancers.

A Patient with Complex Gout with an Autoinflammatory Syndrome and a Sternoclavicular Joint Arthritis as Presenting Symptoms.

A 50-year-old man presented to the emergency department with widespread pain, especially at the chest level, fever, and night sweats. Physical examinations revealed a swelling with localized pain in the left sternoclavicular joint. Laboratory tests showed a CPR of 134 mg/l and an ESR of 70 mm/h. The patient's anamnesis is, for a chronic gouty arthritis, poorly controlled type 2 diabetes and a lumbosacral radicular syndrome. Home therapy includes metformin, sitagliptin, gliclazide, naproxen with partial benefit on pain, and febuxostat. Differential diagnoses of sternoclavicular swelling include infection, crystal or psoriatic arthropathy, tumor pathology, SAPHO syndrome, and osteoarthritis. An ultrasound scan performed at the thoracic level showed the presence of effusion in the sternoclavicular joint. A thoracoabdominal CT scan, performed in doubt of neoplasias, shows no masses but osteostructural nonspecific alterations of the sternoclavicular joint. We performed a dual energy CT (DECT) which reports a gouty arthropathy at the sternoclavicular joints (in the literature, only three similar cases are proved). Because of the poor therapeutic effects using febuxostat and systemic corticosteroids, the patient was treated with anakinra, an interleukin 1 receptor antagonist, which led, 6 months after the event, to a total remission.

Red flags for appropriate referral to the gastroenterologist and the rheumatologist of patients with inflammatory bowel disease and spondyloarthritis.

Collaboration between gastroenterologists and rheumatologists is recommended for the correct management of patients with associated spondyloarthritis (SpA) and inflammatory bowel disease (IBD). We aimed to establish the appropriateness of several red flags for a prompt specialist referral. A systematic review of the literature was performed using the GRADE method to describe the prevalence of co-existing IBD-SpA and the diagnostic accuracy of red flags proposed by a steering committee. Then, a consensus among expert gastroenterologists and rheumatologists (10 in the steering committee and 13 in the expert panel) was obtained using the RAND method to confirm the appropriateness of each red flag as 'major' (one sufficient for patient referral) or 'minor' (at least three needed for patient referral) criteria for specialist referral. The review of the literature confirmed the high prevalence of co-existing IBD-SpA. Positive and negative predictive values of red flags were not calculated, given the lack of available data. A consensus among gastroenterology and rheumatology specialists was used to confirm the appropriateness of each red flag. Major criteria to refer patients with SpA to the gastroenterologist included: rectal bleeding, chronic abdominal pain, perianal fistula or abscess, chronic diarrhoea and nocturnal symptoms. Major criteria to refer patients with IBD to the rheumatologist included: chronic low back pain, dactylitis, enthesitis and pain/swelling of peripheral joints. Several major and minor red flags have been identified for the diagnosis of co-existing IBD-SpA. The use of red flags in routine clinical practice may avoid diagnostic delay and reduce clinic overload.

Does the dry cow treatment with monensin controlled release capsule affect Parmigiano Reggiano cheese production?

We investigated the effects of monensin controlled-release capsule (CRC; Kexxtone, Eli Lilly and Company Ltd., Indianapolis, IN) preventative ketosis treatment on the traditional cheesemaking process as well as the final characteristics of Parmigiano Reggiano (PR) cheese. The use of this prevention product to reduce the incidence of ketosis in transition dairy cows was approved by the European Medicines Agency in 2013. No previous studies are available concerning the effects of this treatment on prolonged-ripening cheese production such as PR. In PR cheese production, feed, feed additives, and cow treatments are strictly regulated to avoid any possible interference with traditional manufacturing processes. For these reasons, on 1 farm where all milk was used for PR cheese production, monensin CRC was administered to 33 cows, 21 d before calving in the monensin-treated group (TRT), whereas untreated cows with similar breed and parity characteristics constituted the control group (CTR). For 20 wk, milk obtained from each group and whey starter were separately managed and transported in the cheese factory, where 2 cheese wheels per group were produced daily, making 552 PR cheese wheels in total. Morning bulk tank milk composition, cheesemaking properties, and whey starter fermentation activities were analyzed twice a week. Every aspect of the cheesemaking process was recorded and the resulting cheese was evaluated after 36 h and 6, 12, and 18 mo from production for yield, texture defects, composition, and fatty acids profile. Milk from the 2 groups differed for somatic cell content (TRT = 3.04 vs. CTR = 4.06, somatic cell score), total bacterial count (TRT = 4.08 vs. CTR = 6.08 × 1,000 cfu/mL), titratable acidity (TRT = 3.66 vs. CTR = 3.72 Soxhlet-Henkel degrees/50 mL), and casein content percentage (TRT = 2.4 vs. CTR = 2.5%). Whey starter parameters were comparable between the 2 groups. Final cheese composition and organoleptic profile were not influenced by the treatment, except for C18:1 content being enhanced (TRT = 22.8 vs. CTR = 20.8% of fatty acids). Percentage of defected ripened cheese was significantly lower in the treated group, both at x-ray evaluation performed at 6 mo (TRT = 6.2 vs. CTR = 12.3%) and at the consortium inspection, performed at 12 mo of ripening (TRT = 1.5 vs. CTR = 6.5%). On the other hand, average cheese yield at 18 mo of ripening was partially reduced (TRT = 7.5 vs. CTR = 7.7%). Overall, the use of monensin CRC had no negative effect on the cheesemaking process, prolonged ripening cheese characteristics, milk composition, or whey starter quality.

A centrally acting antihypertensive, clonidine, combined to a venous dilator, nitroglycerin, to handle severe pulmonary edema.

A patient, with known left ventricular failure presented with severe pulmonary edema, an ejection fraction of 10% to 15%, knee mottling, and lactates of 7 mM L⁻¹. He was treated with unusually high-dose nitroglycerin (NTG) intravenously (IV; NTG ≈ 70 mg for 1 hour). To suppress dyspnea, systolic blood pressure had to be lowered from ≈ 150-160 to ≈ 100-120 mm Hg. To lower NTG requirement, an α-2 agonist, clonidine, was administered (300 µg IV for 2 hours). Dyspnea, tachypnea, and tachycardia subsided for 1 to 2 hours, allowing to reduce NTG infusion to 2 to 4 mg h⁻¹. State-of the-art treatment was superimposed: sitting position with leg down, noninvasive ventilation, positive end-expiratory pressure, bolus of furosemide 250 mg, and administration of 1000 mL of crystalloid for 1 hour under echocardiographic guidance. We ascribed the resistance to NTG to the activation of the sympathetic, vasopressin, and renin-angiotensin systems ("neurohormonal activation"). α-2 agonists reduce the sympathetic activation observed during severe left ventricular failure and overall oxygen consumption, evoke systemic and pulmonary arterial dilation, increase diastolic time, and improve diastolic function and diuresis. Because the α-2 agonist, dexmedetomidine, is available as an IV drug on the North American market, a niche may exist in the setting of emergency medicine/coronary care. This awaits evidence-based documentation.

Bird assemblage mist-netted in an Atlantic Forest area: a comparison between vertically-mobile and ground-level nets.

Mist nets may be opened at different heights in the forest, but they are seldom used over 3 m above the ground. We used two different methods to compare species richness, composition, and relative abundance and trophic structure of the bird assemblage at Ilha Grande (with a 290 birds standardization): conventional ground-level nets (0-2.4 m height range) and elevated nets (0-17 m) with an adjustable-height system (modified from Humphrey et al., 1968) that we call vertically-mobile nets. There were significant differences in capture frequencies between methods for about 20% of the species (Chi-squared test, P<0.05), and the two methods caught different assemblages. Ground-level nets recorded less species, and they comparatively overestimated mainly Suboscine insectivores and underestimated frugivores and nectarivores. Different sampling methods used at the same location may result in very different diagnoses of the avifauna present, both qualitatively and quantitatively. We encourage studies involving mist net sampling to include the upper strata to more accurately represent the avifauna in Atlantic Forest.

Characterization of microsatellite markers for the Restinga Antwren, Formicivora littoralis (Thamnophilidae), an endangered bird endemic to Brazil.

Molecular markers are important tools in determining parentage, gene flow, and the genetic structure of species. In the case of rare, endemic, and/or threatened species, these markers can be used to understand key ecological questions and support conservation actions. We developed seven microsatellite markers for the only bird endemic to the Restinga ecosystem. Microsatellite loci were isolated from a library that was based on 10 individuals (six males and four females). Primers were tested in 107 individuals of the same population. The number of alleles per locus ranged from 4 to 19, and the observed and expected heterozygosity varied from 0.15 to 0.84 and from 0.60 to 0.89, respectively. We expect that the polymorphic microsatellite loci we describe will be useful for other studies, particularly in the Tropics.

Review article: newer optical and digital chromoendoscopy techniques vs. dye-based chromoendoscopy for diagnosis and surveillance in inflammatory bowel disease.

BACKGROUND: Recent innovations in gastrointestinal endoscopy have changed our traditional approach to diagnosis and therapy in patients with inflammatory bowel diseases (IBD). While traditionally used dye-based chromoendoscopy (DBC) techniques suffer from several limitations that reduce their utility in daily routine practice, newer 'dye-less' chromoendoscopy (DLC) techniques offer a great potential to overcome most of these limitations. AIM: To review available optical and digital chromoendoscopy techniques, by critically discussing their potential for diagnostic and surveillance colonoscopy in patients with IBD. METHODS: A literature search on the use of dye-less and dye-based chromoendoscopy in IBD patients was performed. RESULTS: In long-standing IBD, DBC improves detection of dysplasia (diagnostic odds ratio = 17.5, 95% CI = 1.2-247.1) as well as prediction of inflammatory disease activity and extent of disease compared with standard video-colonoscopy. Narrow band imaging (NBI) shows no improvement in dysplasia detection rates compared with white-light endoscopy and DBC (P = 0.6). Moreover, NBI results in a suboptimal differentiation of dysplastic from nondysplastic lesions. No data regarding digital DLC techniques (i.e. FICE, i-scan) for dysplasia detection in IBD are yet available. Both NBI and i-scan are superior to white-light endoscopy in assessing the activity and extent of colorectal IBD. CONCLUSIONS: Although the potential benefits of newer optical and digital dye-less chromoendoscopy techniques over traditionally used DBC are substantial, only DBC can currently be recommended to improve dysplasia detection in long-standing IBD. In contrast, DLC has the potential to quantify disease activity and mucosal healing in IBD.

Effect of immunosuppressive therapy on patients with inflammatory bowel diseases and hepatitis B or C virus infection.

Viral hepatitis reactivation has been widely reported in patients undergoing immunosuppressive therapy; however, few data are available about the risk of HBV and HCV reactivation in patients with inflammatory bowel disease, receiving immunosuppressive drugs. The aim of our study was to assess the prevalence of HBV and HCV infection in a consecutive series of patients with inflammatory bowel disease and to value the effects of immunosuppressive therapy during the course of the infection. Retrospective observational multicenter study included all consecutive patients with inflammatory bowel disease who have attended seven Italian tertiary referral hospitals in the last decade. A total of 5096 patients were consecutively included: 2485 Crohn's disease and 2611 Ulcerative Colitis. 30.5% and 29.7% of the patients were investigated for HBV and HCV infection. A total of 30 HBsAg positive, 17 isolated anti-HBc and 60 anti-HCV-positive patients were identified. In all, 20 patients with HBV or HCV infection received immunosuppressive therapy (six HBsAg+; four isolated anti-HBc+ and 10 anti-HCV+). One of six patients showed HBsAg+ and one of four isolated anti-HBc+ experienced reactivation of hepatitis. Two of six HBsAg patients received prophylactic therapy with lamivudine. Only one of 10 anti-HCV+ patients showed mild increase in viral load and ALT elevation. Screening procedures for HBV and HCV infection at diagnosis have been underused in patients with inflammatory bowel disease. We confirm the role of immunosuppressive therapy in HBV reactivation, but the impact on clinical course seems to be less relevant than previous reported.

Atypical esophageal vascular lesions observed in liver cirrhosis.

Chronic liver disease is known to be associated with several vascular alterations including portal hypertension and hepato-pulmonary insufficiency. We report a case of esophageal vascular lesions resembling spider naevi in a patient with nonalcoholic cirrhosis who underwent an upper gastrointestinal (GI) endoscopy. We observed the presence of multiple white round elevations, 5-6 mm in size, with radiating thin-walled vessels, in the middle and distal esophagus. The histological examination documented the presence of multiple dilated blood vessels in the mucosal layer of the esophagus, with striking thickening of the endothelium wall. There was no evidence of esophagogastric varices, but only of a moderate congestive antral gastropathy. To our knowledge, these endoscopic esophageal findings have not yet been described in cirrhosis.

Early-onset seizure variant of Rett syndrome: definition of the clinical diagnostic criteria.

BACKGROUND: Rett syndrome is a severe neurodevelopmental disorder affecting almost exclusively females. Among Rett clinical variants, the early-onset seizure variant describes girls with early onset epilepsy and it is caused by mutations in CDKL5. METHODS: Four previously reported girls and five new cases with CDKL5 mutation, ranging from 14 months to 13 years, were evaluated by two clinical geneticists, classified using a severity score system based on the evaluation of 22 different clinical signs and compared with 128 classic Rett and 25 Zappella variant MECP2-mutated patients, evaluated by the same clinical geneticists. Clinical features were compared with previously described CDKL5 mutated patients. Both the statistical and the descriptive approach have been used to delineate clinical diagnostic criteria. RESULTS: All girls present epilepsy with onset varying from 10 days to 3 months. Patients may present different type of seizures both at onset and during the whole course of the disease; multiple seizure types may also occur in the same individual. After treatment with antiepileptic drugs patients may experience a short seizure-free period but epilepsy progressively relapses. Typical stereotypic hand movements severely affecting the ability to grasp are present. Psychomotor development is severely impaired. In the majority of cases head circumference is within the normal range both at birth and at the time of clinical examination. CONCLUSION: For the practical clinical approach we propose to use six necessary and eight supportive diagnostic criteria. Epilepsy with onset between the first week and 5 months of life, hand stereotypies, as well as severe hypotonia, are included among the necessary criteria.

Copine-III interacts with ErbB2 and promotes tumor cell migration.

ErbB2 amplification and overexpression in breast cancer correlates with aggressive disease and poor prognosis. To find novel ErbB2-interacting proteins, we used stable isotope labeling of amino acids in cell culture followed by peptide affinity pull-downs and identified specific binders using relative quantification by mass spectrometry. Copine-III, a member of a Ca(2+)-dependent phospholipid-binding protein family, was identified as binding to phosphorylated Tyr1248 of ErbB2. In breast cancer cells, Copine-III requires Ca(2+) for binding to the plasma membrane, where it interacts with ErbB2 upon receptor stimulation, an interaction that is dependent on receptor activity. Copine-III also binds receptor of activated C kinase 1 and colocalizes with phosphorylated focal adhesion kinase at the leading edge of migrating cells. Importantly, knockdown of Copine-III in T47D breast cancer cells causes a decrease in Src kinase activation and ErbB2-dependent wound healing. Our data suggest that Copine-III is a novel player in the regulation of ErbB2-dependent cancer cell motility. In primary breast tumors, high CPNE3 RNA levels significantly correlate with ERBB2 amplification. Moreover, in an in situ tissue microarray analysis, we detected differential protein expression of Copine-III in normal versus breast, prostate and ovarian tumors, suggesting a more general role for Copine-III in carcinogenesis.

[Validity of carbohydrate-deficient transferrine (CDT) in assessing chronic abuse of ethyl alcohol in urban public transport workers]. / Validità della transferrina decarboidrata (CDT) nell'accertamento dell'abuso cronico di alcol etilico in addetti al trasporto pubblico urbano.

OBJECTIVES: The aim of this study was to verify the ability of some chemical-clinical parameters, with particular emphasis on carbohydrate-deficient transferrin (CDT), in assessing chronic abuse of ethanol in a group of urban public transport workers. METHODS: In the 512 subjects, public transport tram drivers, all males, who entered the study, information on the intake of alcoholic beverages was collected during the periodical health surveillance controls performed according to Italian legislation (DM88/99). In the study subjects the following clinical-chemical parameters were measured: CDT gamma-glutamyltransferase (GGT), mean corpuscular volume of erythrocytes (MCV), aspartate aminotransferase (AST), alanine aminotransferase (ALT). RESULTS: The subjects were divided into five groups according to different levels of alcohol intake: non-drinkers, occasional drinkers, moderate drinkers, habitual drinkers and heavy drinkers. The median values of CDT GGT and MCV were higher in drinkers than in non-drinkers, with an increasing trend in proportion to the amount of ethanol ingested. The validity of each parameter in determining chronic abuse of ethyl alcohol was calculated taking as true the statement on alcohol intake made spontaneously by the subject. CDT was confirmed as the parameter with the best sensitivity and specificity: 90% and 98%, respectively, the negative predictive value was 99%, while the positive predictive power was 45%. The combination of CDT with GGT or MCV led to small improvements in the positive predictive ability, which reached 50% for CDT and MCV and 60% for CDT and GGT. CONCLUSIONS: Our results confirmed that, also in the workplace, CDT is the most important parameter for the diagnosis of chronic abuse of alcohol intake, but also showed that the positivity of this marker cannot be taken as certainty of abuse. The adoption of further diagnostic tools is therefore proposed, such as a specific questionnaire to collect information on alcohol intake, and in case of positive CDT a second-level test with a high specificity.