Authorship of Italian medical literature on neuroendocrine neoplasms: any gender gap?

PURPOSE: While males have dominated the physician lines over the last decades the recent female doctors' number increasing might progressively reduce this gender gap. This might be not fully true in the academic/research area. We aimed to analyze the gender distribution of first/senior Italian authors on neuroendocrine neoplasm papers published on peer reviewed journals. METHODS: Publications from January 2019 to September 2023 were reviewed; only papers with first and/or senior Italian authors were included. First/senior author gender, type of article, co-authorship with foreign authors were the variable analyzed. RESULTS: 742 papers with Italian first and/or senior authors were retrieved, 449 (60.5%) multicentric, 285 (38.4%) original articles. A female author was first and senior author in 386/742 (52%) and in 228/742 (31%) papers, respectively. 150 (20.2%) papers included foreign coauthors, being an Italian female researcher first author in 50 papers (33%), senior author in 28 (18.6%). The number of Italian female first/senior authors has been increasing over the years (22 in 2019, 113 in 2022; 16 in 2019, 62 in 2022, respectively). The first/senior female authors were mainly Oncologists/Endocrinologists/Pathologists rather than Gastroenterologists/Nuclear Medicine doctors/Surgeons/Radiologists. CONCLUSION: There has been an increase in the prevalence of female authorship of published research in the neuroendocrine setting over the last 5 years, which partially reflects the current distributions in this field, taking into account that several specialties with different gender distribution are involved. However, senior authorship continues to be primarily men. Efforts should be made to improve proportionate gender representation in both clinical and academic/research setting.

A critical analysis of the CFD-DEM simulation of pharmaceutical aerosols deposition in upper intra-thoracic airways: Considerations on air flow.

A well-corroborated numerical methodology ensuring reproducibility in the modeling of pharmaceutical aerosols deposition in the respiratory system via CFD-DEM simulations within the RANS framework is currently missing. Often, inadequately clarified assumptions and approximations and the lack of evidences on their quantitative impact on the simulated deposition phenomenology, make a direct comparison among the different theoretical studies and the limited number of experiments a very challenging task. Here, with the ultimate goal of providing a critical analysis of some crucial computational aspects of aerosols deposition, we address the issues of velocity fluctuations propagation in the upper intra-thoracic airways and of the persistence of secondary flows using the SimInhale reference benchmark. We complement the investigation by describing how methodologies used to drive the flow through a truncated lung model may affect numerical results and how small discrepancies are observed in velocity profiles when comparing simulations based on different meshing strategies.

FLT3-targeted therapy restores GATA1 pathway function in NPM1/FLT3-ITD mutated acute myeloid leukaemia.

One-third of newly diagnosed adult acute myeloid leukaemia (AML) carry FLT3 mutations, which frequently occur together with nucleophosmin (NPM1) mutations and are associated with worse prognosis. FLT3 inhibitors are widely used in clinics with limitations due to drug resistance. AML cells carrying FLT3 mutations in both mouse models and patients present low expression of GATA1, a gene involved in haematopoietic changes preceding AML. Here, we show that FLT3 inhibition induces cellular responses and restores the GATA1 pathway and functions in NPM1/FLT3-ITD mutated AML, thus providing a new mechanism of action for this drug.

One-year efficacy of a lifestyle behavioural intervention on physical and mental health in people with severe mental disorders: results from a randomized controlled trial.

This multicentric randomized controlled trial (RCT), carried out in six Italian University mental health sites, aims to test the efficacy of a six-month psychosocial intervention (LYFESTYLE) on Body Mass Index (BMI), body weight, waist circumference, fasting glucose, triglycerides, cholesterol, Framingham and HOmeostasis Model Assessment of insulin resistance (HOMA-IR) indexes in patients with schizophrenia, bipolar disorder, and major depression. Moreover, the efficacy of the intervention has also been tested on several other physical and mental health domains. Patients were randomly allocated to receive the six-month experimental intervention (LIFESTYLE) or a behavioural control intervention. All enrolled patients were assessed at baseline and after one year. We recruited 401 patients (206 in the experimental and 195 in the control group) with a diagnosis of schizophrenia or other psychotic disorder (29.9%), bipolar disorder (43.3%), or major depression (26.9%). At one year, patients receiving the experimental intervention reported an improvement in body mass index, body weight, waist circumference, HOMA-IR index, anxiety and depressive symptoms and in quality of life. Our findings confirm the efficacy of the LIFESTYLE intervention in improving physical and mental health-related outcomes in patients with severe mental illnesses after one year.

Helminth community structure of the white-bellied woolly mouse opossum Marmosa constantiae Thomas, 1904 in Central-West Brazil.

Marmosa constantiae is a species of marsupial restricted to the central portion of South America. In Brazil, it occurs in the northwestern region including five states of the Amazon, Cerrado, and Pantanal biomes. However, there is no study of the helminth fauna or helminth community structure for this marsupial. The aims of this study were to describe the species composition and to analyse the structure of the helminthic community of M. constantiae in an area of the Amazon Arc in Sinop, north of the state of Mato Grosso, Brazil. Parasites were searched in 53 specimens of this marsupial, among which 44 were infected with at least one helminth species. Parasitic helminths were counted and identified. Nine species were collected: seven nematodes, one cestode, and one acanthocephalan. The most abundant species were Gracilioxyuris agilisis, Travassostrongylus scheibelorum, Pterygodermatites sinopiensis, and Subulura eliseae. These species were the only dominant ones in the component community. No significant differences were observed in the abundance and prevalence of helminths between male and female hosts. Host body size significantly influenced helminth abundance in males. The pattern of community structure considering the infracommunities in this locality indicated more species replacement than species loss along the environmental gradient. This is the first study to report the helminth fauna and the helminth community structure of M. constantiae.

Upgrades of Genetic Programming for Data-Driven Modeling of Time Series.

In many engineering fields and scientific disciplines, the results of experiments are in the form of time series, which can be quite problematic to interpret and model. Genetic programming tools are quite powerful in extracting knowledge from data. In this work, several upgrades and refinements are proposed and tested to improve the explorative capabilities of symbolic regression (SR) via genetic programming (GP) for the investigation of time series, with the objective of extracting mathematical models directly from the available signals. The main task is not simply prediction but consists of identifying interpretable equations, reflecting the nature of the mechanisms generating the signals. The implemented improvements involve almost all aspects of GP, from the knowledge representation and the genetic operators to the fitness function. The unique capabilities of genetic programming, to accommodate prior information and knowledge, are also leveraged effectively. The proposed upgrades cover the most important applications of empirical modeling of time series, ranging from the identification of autoregressive systems and partial differential equations to the search of models in terms of dimensionless quantities and appropriate physical units. Particularly delicate systems to identify, such as those showing hysteretic behavior or governed by delayed differential equations, are also addressed. The potential of the developed tools is substantiated with both a battery of systematic numerical tests with synthetic signals and with applications to experimental data.

Targeting neuroendocrine tumors with octreotide and lanreotide: Key points for clinical practice from NET specialists.

Octreotide and lanreotide are the two somatostatin analogs (SSA) currently available in clinical practice. They have been approved first to control the clinical syndrome (mainly carcinoid syndrome) associated with functioning neuroendocrine tumors (NET) and later for tumor growth control in advanced low/intermediate grade NET. Although evidence regarding their role, especially as antiproliferative therapy, has been increasing over the years some clinical indications remain controversial. Solicited by AIOM (Italian Association of Medical Oncology) a group of clinicians from various specialties, including medical oncology, endocrinology, and gastroenterology, deeply involved in NET for their clinical and research activity, addressed eight open questions, critically reviewing evidence and guidelines and sharing clinical take-home messages. The questions regarded the use of long-acting octreotide and lanreotide in the following settings: functioning and non-functioning NET refractory to label dose, first-line metastatic pulmonary NET, combination with other therapy with an antiproliferative intent, maintenance in NET responding to other therapies, adjuvant treatment, Ki-67-related cut-off, somatostatin receptor imaging, safety, and feasibility. The level of evidence is not absolute for the majority of these clinical contexts, so it is recommended to distinguish routine versus sporadic utilization in very selected cases. Mention of such specific issues by the main European guidelines (ENETS, European Neuroendocrine Tumor Society, and ESMO, European Society for Medical Oncology) was explored and their position reported. However, different clinical decisions on single patients could be made if the case is carefully discussed within a NET-dedicated multidisciplinary team.

Sporadic and MEN1-related gastrinoma and Zollinger-Ellison syndrome: differences in clinical characteristics and survival outcomes.

PURPOSE: Gastrinoma with Zollinger-Ellison syndrome (ZES) may occur sporadically (Sp) or as part of the inherited syndrome of multiple endocrine neoplasia 1 (MEN-1). Data comparing Sp and MEN-1/ZES are scanty. We aimed to identify and compare their clinical features. METHODS: Consecutive patients with ZES were evaluated between 1992 and 2020 among a monocentric Italian patient cohort. RESULTS: Of 76 MEN-1 patients, 41 had gastroenteropancreatic neuroendocrine neoplasm (GEP-NEN), 18 of whom had ZES; of 320 Sp-GEP-NEN, 19 had Sp-ZES. MEN-1/ZES patients were younger (p = 0.035) and the primary MEN-1/ZES gastrinoma was smaller than Sp-ZES (p = 0.030). Liver metastases occurred in both groups, but only Sp-ZES developed extrahepatic metastases. 13 Sp-ZES and 8 MEN-1/ZES underwent surgery. 8 Sp-ZES and 7 MEN-1/ZES received somatostatin analogs (SSAs). Median overall survival (OS) was higher in MEN-1/ZES than in Sp-ZES (310 vs 168 months, p = 0.034). At univariate-logistic regression, age at diagnosis (p = 0.01, OR = 1.1), G3 grading (p = 0.003, OR = 21.3), Sp-ZES (p = 0.02, OR = 0.3) and presence of extrahepatic metastases (p = 0.001, OR = 7.2) showed a significant association with OS. At multivariate-COX-analysis, none of the variables resulted significantly related to OS. At univariate-logistic regression, age (p = 0.04, OR = 1.0), size (p = 0.039, OR = 1.0), G3 grade (p = 0.008, OR = 14.6) and extrahepatic metastases (p = 0.005, OR = 4.6) were independently associated with progression-free survival (PFS). In multivariate-COX-analysis, only extrahepatic metastases (p = 0.05, OR = 3.4) showed a significant association with PFS. Among SSAs-treated patients, MEN-1/ZES showed better PFS (p = 0.0227). After surgery, the median PFS was 126 and 96 months in MEN-1 and Sp, respectively. CONCLUSION: MEN-1/ZES patients generally show better OS and PFS than Sp-ZES as well as better SSAs response.

Intranasal SARS-CoV-2 RBD decorated nanoparticle vaccine enhances viral clearance in the Syrian hamster model.

Multiple vaccines have been developed and licensed for SARS-CoV-2. While these vaccines reduce disease severity, they do not prevent infection, and SARS-CoV-2 continues to spread and evolve. To prevent infection and limit transmission, vaccines must be developed that induce immunity in the respiratory tract. Therefore, we performed proof-of-principle vaccination studies with an intranasal nanoparticle vaccine against SARS-CoV-2. The vaccine candidate consisted of the self-assembling 60-subunit I3-01 protein scaffold covalently decorated with the SARS-CoV-2 receptor binding domain (RBD) using the SpyCatcher-SpyTag system. We verified the intended antigen display features by reconstructing the I3-01 scaffold to 3.4A using cryo-EM, and then demonstrated that the scaffold was highly saturated when grafted with RBD. Using this RBD-grafted SpyCage scaffold (RBD+SpyCage), we performed two unadjuvanted intranasal vaccination studies in the "gold-standard" preclinical Syrian hamster model. Hamsters received two vaccinations 28 days apart, and were then challenged 28 days post-boost with SARS-CoV-2. The initial study focused on assessing the immunogenicity of RBD+SpyCage, which indicated that vaccination of hamsters induced a non-neutralizing antibody response that enhanced viral clearance but did not prevent infection. In an expanded study, we demonstrated that covalent bonding of RBD to the scaffold was required to induce an antibody response. Consistent with the initial study, animals vaccinated with RBD+SpyCage more rapidly cleared SARS-CoV-2 from both the upper and lower respiratory tract. These findings demonstrate the intranasal SpyCage vaccine platform can induce protection against SARS-CoV-2 and, with additional modifications to improve immunogenicity, is a versatile platform for the development of intranasal vaccines targeting respiratory pathogens.

A critical analysis of the CFD-DEM simulation of pharmaceutical aerosols deposition in extra-thoracic airways.

Recent advances in the characterization of the human respiratory system and in multi-phase flow dynamics in complex geometries have led numerical simulations to play an expanding role for exploring aerosol deposition mechanisms in the lungs. However, the development of an efficient numerical and mathematical description is far from unique, and determining which aspects of the modelling are critical and which details are essentially irrelevant is indeed a difficult task. With the aim of addressing this lack of a rationalized framework, we propose a systematic analysis of pharmaceutical aerosols deposition in the extra-thoracic airways, focusing on several important modelling aspects whose related assumptions and approximations have not always been sufficiently discussed and clarified. We consider the importance of intrinsic time dependent fluctuations of the air flow, highlighting how their contribution in aerosol deposition is as important as the particle-turbulence interaction one. We show how sensitive the turbulence intensity can be to the meshing strategy and how aerosol deposition can be influenced by the latter choice. We demonstrate how a swirling air jet can enhance extra-thoracic deposition compared to a straight one, and how different the deposition patterns can be in case a realistic inhalation profile and aerosol plume are employed.

Subulura eliseae sp. n. (Ascaridida: Subuluroidea), a parasite of Marmosa spp. from Amazon rainforest, Brazil.

The parasite biodiversity of mouse opossums in Brazil remains incompletely explored. We describe a new species of Subulura (Ascaridida: Subuluroidea) from the large intestine of the white-bellied woolly mouse opossum, Marmosa constantiae, based on the results of light and scanning electron microscopy (SEM). We also partially sequenced the mitochondrial cytochrome c oxidase I (MT-CO1) gene of the new species, using molecular phylogenetic analyses to determine its relationships within the Subuluroidea superfamily. As molecular data on subuluroid species are extremely limited, few inferences could be drawn from our phylogenies. Our SEM observations showed the detailed morphology of the cephalic extremity, precloacal pseudo-sucker, caudal papillae, phasmids and vulva. Subulura eliseae sp. n. differs from the other four Subulura parasites species of marsupials by the number of caudal papillae and the structure dimensions, and size of the spicule. Moreover, S. eliseae sp. n. has ten pairs of caudal papillae, which is unique compared to other species. We present morphometric and molecular data on this new species, contributing to future studies on subuluroids.

Sexuality in breast cancer survivors: sexual experiences, emotions, and cognitions in a group of women under hormonal therapy.

BACKGROUND: Earlier diagnosis and improved treatments have led to better outcomes in breast cancer, making quality of life a key issue. Sexuality represents a pillar of quality of life, although it is often neglected by both healthcare providers and patients when it comes to cancer. This study aims to explore the differences in sexual functioning, distress, psychopathology, emotions, and cognitions between breast cancer patients under hormonal treatment and controls. METHODS: Seventy-nine women (age range between 24 and 69 years) in hormonal therapy for breast cancer completed a self-reported protocol. A matched control group of 103 women was randomly extracted from an Italian general population database. Eight self-report questionnaires exploring biopsychosocial factors were administered. RESULTS: The current study showed an impaired sexuality in breast cancer patients compared to controls. Breast cancer women under hormonal treatment were characterized by diminished or absent sexual activity (chi2 = 36.16; p < 0.001), lower level of sexual functioning in all areas except for pain (F(1,180) = 8.1; p < 0.01), higher sexual (F(1,180) = 10.08; p < 0.001) and psychological distress (F(1,180) = 6.23; p < 0.05), higher scores in Difficulties in Identifying Feelings (F(1,180) = 7.31; p < 0.01) and Externally Oriented Thinking (F(1,180) = 6.64; p < 0.05), higher level of negative emotions related to sexuality (F(1,180) = 11.13; p < 0.001), and more rigid cognition towards peculiar aspects of sexuality, such as Failure Disengagement Thoughts (F(1,180) = 22.01; p < 0.001) and Age related Beliefs (F(1,180) = 5.7; p < 0.05). CONCLUSIONS: Health care providers do not usually assess those issues in their routine practice, so that sexuality remains an unmet need with remarkable effects on general health and quality of life.

["Pediatric inflammatory multisystem syndrome"-Experiences from a Berlin Children's Hospital]. / "Pediatric inflammatory multisystem syndrome" ­ Erfahrungen aus einer Berliner Kinderklinik.

BACKGROUND: Since the beginning of the SARS-CoV­2 pandemic, cases of the hyperinflammatory syndrome pediatric inflammatory multisystem syndrome (PIMS) have been accumulating. The clinical presentation is variable and it occurs 2-6 weeks after infection with SARS-CoV­2. As of today, immunoglobulins and/or steroids as well as ASS are used for medication. METHOD: In our clinic 11 patients presented with PIMS between 06/2020 and 06/2021, whose data were retrospectively collected and analyzed. RESULTS: Of the 11 patients 6 were male, the age distribution ranged from 4-18 years and 7 were overweight or obese. Almost all patients showed gastrointestinal and cardiovascular involvement, 4 had respiratory symptoms, 6 showed signs of nephritis. All showed blood count changes with anemia or leukocytosis and coagulopathy. CRP, ferritin, and soluble IL2 receptor were highly elevated in all patients. Only 2 patients had neither troponin­T nor NT-pro-BNP elevation and 7 patients had impaired left ventricular function. Positive SARS-CoV­2 serology was found in 10, and positive SARS-CoV­2 PCR via nasopharyngeal swabs in 2.All were initially treated with antibiotics, 3 patients required O2 supplementation, 6 required intensive care and 5 required vasoactive agents. All but one patient received immunoglobulins and ASS, 5 received prednisolone. Length of stay ranged from 4-51 days. CONCLUSION: PIMS is a severe acute hyperinflammatory disease, which was secured in 11 patients in our clinic. In some cases, there was a need for intensive care. Under anti-inflammatory therapy there was a good response without exception.

Second primary neoplasms in patients with lung and gastroenteropancreatic neuroendocrine neoplasms: Data from a retrospective multi-centric study.

BACKGROUND: Patients with sporadic neuroendocrine neoplasms may exhibit a higher risk of a second primary tumor than the general population. AIM: This study aimed to analyze the occurrence of second primary malignancies. METHODS: A retrospective cohort of 2757 patients with sporadic lung and gastro-entero-pancreatic neuroendocrine neoplasms, managed at eight Italian tertiary referral Centers, was included. RESULTS: Between 2000 and 2019, a second primary malignancy was observed in 271 (9.8%) neuroendocrine neoplasms patients with 32 developing a third tumor. There were 135 (49.8%) females and the median age was 64 years. The most frequent locations of the second tumors were breast (18.8%), prostate (12.5%), colon (9.6%), blood tumors (8.5%), and lung (7.7%). The second primary tumor was synchronous in 19.2% of cases, metachronous in 43.2%, and previous in 37.6%. As concerned the neuroendocrine neoplasms, the 5- and 10-year survival rates were 87.8% and 74.4%, respectively. PFS for patients with a second primary malignancy was shorter than for patients without a second primary malignancy. Death was mainly related to neuroendocrine neoplasms. CONCLUSION: In NEN patients the prevalence of second primary malignancies was not negligible, suggesting a possible neoplastic susceptibility. Overall survival was not affected by the occurrence of a second primary malignancy.

Risk of preoperative understaging of duodenal neuroendocrine neoplasms: a plea for caution in the treatment strategy.

PURPOSE: Pretreatment staging is the milestone for planning either surgical or endoscopic treatment in duodenal neuroendocrine neoplasms (dNENs). Herein, a series of surgically treated dNEN patients was evaluated to assess the concordance between the pre- and postsurgical staging. METHODS: Retrospective analysis of patients with a histologically confirmed diagnosis of dNENs, who underwent surgical resection observed at eight Italian tertiary referral centers. The presurgical TNM stage, based on the radiological and functional imaging, was compared with the pathological TNM stage, after surgery. RESULTS: From 2000 to 2019, 109 patients were included. Sixty-six patients had G1, 26 a G2, 7 a G3 dNEN (Ki-67 not available in 10 patients). In 46/109 patients (42%) there was disagreement between the pre- and postsurgical staging, being it understaged in 42 patients (38%), overstaged in 4 (3%). As regards understaging, in 25 patients (22.9%), metastatic loco-regional nodes (N) resulted undetected at both radiological and functional imaging. Understaging due to the presence of distal micrometastases (M) was observed in 2 cases (1.8%). Underestimation of tumor extent (T) was observed in 12 patients (11%); in three cases the tumor was understaged both in T and N extent. CONCLUSIONS: Conventional imaging has a poor detection rate for loco-regional nodes and micrometastases in the presurgical setting of the dNENs. These results represent important advice when local conservative approaches, such as endoscopy or local surgical excision are considered and it represents a strong recommendation to include endoscopic ultrasound in the preoperative tools for a more accurate local staging.

Short communication: Comparative performance of 3 on-farm culture systems for detection of mastitis pathogens interpreted by trained and untrained observers.

On-farm culture (OFC) systems facilitate pathogen-based mastitis management and can facilitate antimicrobial stewardship on dairy farms. Interpretation of the results, however, may present a challenge for those with limited microbiology experience. Here, we compared results of 3 OFC systems interpreted by trained and untrained observers against results of a standard laboratory reference method (aerobic culture and mass spectrometry). Milk samples (280 quarter and 60 composite) were selected from submissions for routine diagnostic testing to Quality Milk Production Services (Cornell University, Ithaca, NY) between August 2017 and January 2018. Samples were cultured simultaneously using the standard laboratory reference method and 3 commercially available OFC systems that varied in detail of pathogen identification (provided in parentheses) as follows: (1) Minnesota Easy Culture System II Bi-plate (University of Minnesota Laboratory for Udder Health, St. Paul; gram-positive, gram-negative), (2) Minnesota Easy Culture System II Tri-plate (gram-positive, gram-negative, some genus level), and (3) FERA Diagnostics and Biologicals AccuMast plate (Ithaca, NY; genus level, some species level). After 18 to 24 h of incubation, OFC plates were interpreted by 1 trained observer (>10 yr of experience in milk microbiology) and 6 untrained observers with no previous milk microbiology training, using only the manufacturers' instructions for guidance. Strength of agreement (κ) between observer groups and the reference method was determined for the available outcomes of each system. Interpreted by the trained observer, agreement was moderate for identifying gram-positive organisms (Bi-plate, κ = 0.56) and substantial for Streptococcus spp. (Tri-plate, κ = 0.64, AccuMast κ = 0.61). Interpretation by untrained observers resulted in fair agreement (κ = 0.29-0.37) for these organisms. Moderate agreement (κ = 0.43-0.59) was found across all 3 OFC for the identification of gram-negative organisms (Bi-plate), non-aureus staphylococci (Tri-plate and AccuMast), Lactococcus spp., and Enterococcus spp. (AccuMast) when interpreted by the trained observer, and fair to moderate agreement was found (κ = 0.31-0.53) among untrained observers. Across all 3 OFC, agreement was almost perfect (κ = 0.80-0.89) for Staphylococcus aureus for the trained observer, and moderate to substantial (κ = 0.56-0.61) for untrained observers. We concluded that all 3 OFC appeared suitable to support pathogen-based mastitis management when operated by trained observers. Training beyond the instruction manual is a prerequisite to make OFC systems useful for pathogen-based mastitis management.

Childhood family stress and adult resilience in a sample of depressed patients.

BACKGROUND: The aim of this study is to explore the effect of childhood family stress on depression, personal, and social resilience in depressed patients. METHODS: We assessed childhood family stress (RFQ), depression (BSI, depression subscale), and resilience (RSA) in 152 depressed patients, 70 males, and 82 females. We calculated the 33rd and 66th percentiles of RFQ scores to divide the sample among Low, Medium, and High RFQ subgroups. A one-way ANOVA has been carried out to explore the differences between the variables in the subgroups. Finally, two regression analyses with depression, as the dependent variable, and resilience, divided for stress-sensitive and no stress-sensitive factors as independent variables, have been implemented. RESULTS: The one-way ANOVA showed that the Low subgroup had a positive profile, the Medium had an intermediate profile, while the High had a negative one for depression, personal (structured style and social competence), and interpersonal (social resources) resilience. The other factors (perception of self, planned future, and family cohesion) did not show differences in the subgroups, suggesting they are no stress sensitive. Regression analysis showed that no stress-sensitive factors have a constant and significant predictive value for depression in all subgroups; while, stress-sensitive ones showed a growing predictive value for depression from Low to Medium, but not in High, suggesting a ceiling effect. LIMITATIONS: The use of self-report measures, the cross-sectional nature of the study, and the lack of a non-clinical and/or outpatient samples. CONCLUSIONS: This study provides a contribution to the understanding of the effect of childhood family stress on adult resilience and depression.

Super-high magnification dermoscopy can aid the differential diagnosis between melanoma and atypical naevi.

BACKGROUND: Dermoscopy is the most widely used noninvasive imaging technique for the clinical diagnosis of melanoma (MM). Super-high (× 400) magnification dermoscopy (D400) has recently been developed; compared with traditional dermoscopy, it can reveal additional features, down to the identification of single melanocytes in the skin. OBJECTIVES: To evaluate which structures are visible at D400 and to compare them in atypical naevi and MMs. METHODS: A prospective observational multicentre study was conducted. We enrolled patients who were identified as having atypical melanocytic skin lesions by clinical and/or × 20 magnification dermoscopy (D20) examination, and who were assigned to either excision or follow-up. Lesions were imaged by videodermoscopy at D20 and D400. The presence of pigmented cells and their features were assessed at D400. RESULTS: In total, there were 79 patients with 57 naevi and 31 MMs. Of the total 88 lesions, 63 (71.6%) were given a histological diagnosis, while the others were followed up for ≥ 12 months, during which they showed no change and were all diagnosed as naevi. Pigmented cells were identified in > 90% of the lesions at D400. Compared with naevi, MMs had a higher frequency of scattered, large, irregular (in shape and size), dendritic/roundish, violet/blue pigmented cells under D400 (P < 0.001). Moreover, dots (P < 0.01), out-of-focus blue structureless areas (P < 0.01) and vessels (P < 0.001) were also more frequent in MMs than in naevi at D400. CONCLUSIONS: This study showed that D400 can reveal many elements not otherwise visible in traditional D20 dermoscopy, such as pigmented cells and their morphology, which could be useful for the diagnosis of MM.

The interaction of Na+, K+, and phosphate with the gastric H,K-ATPase. Kinetics of E1-E2 conformational changes assessed by eosin fluorescence measurements.

H,K-ATPase and Na,K-ATPase show the highest degree of sequence similarity among all other members of the P-type ATPases family. To explore their common features in terms of ligand binding, we evaluated conformational transitions due to the binding of Na+, K+ and Pi in the H,K-ATPase, and compared the results with those obtained for the Na,K-ATPase. This work shows that eosin fluorescence time courses provide a reasonably precise method to study the kinetics of the E1-E2 conformational changes in the H,K-ATPase. We found that, although Na+ shifts the equilibrium toward the E1 conformation and seems to compete with H+ in ATPase activity assays, it was neither possible to isolate a Na+-occluded state, nor to reveal an influx of Na+ related to H,K-ATPase activity. The high rate of the E2K â†’ E1 transition found for the H,K-ATPase, which is not compatible with the presence of a K+-occluded form, agrees with the negligible level of occluded Rb+ (used as a K+ congener) found in the absence of added ligands. The use of vanadate and fluorinated metals to induce E2P-like states increased the level of occluded Rb+ and suggests that-during dephosphorylation-the probability of K+ to remain occluded increases from the E2P-ground to the E2P-product state. From kinetic experiments we found an unexpected increase in the values of kobs for E2P formation with [Pi]; consequently, to obey the Albers-Post model, the binding of Pi to the E2 state cannot be a rapid-equilibrium reaction.