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Optimal specimen handling is essential for the accurate interpretation of biopsies and cytologic preparations obtained in the course of evaluating the patient with lung disease. Sampling techniques available include bronchoscopy, transthoracic needle core biopsy or aspiration, and surgical wedge biopsy of peripheral lung through a transthoracic approach. In this chapter specimen characteristics and processing steps are presented for each of the common lung samples taken in the course of clinical evaluation for pulmonary disease. Also, for each type of sample the benefits and limitations are reviewed. Such a working knowledge of specimen handling for each procedure ensures the greatest likelihood of success in establishing a specific diagnosis and, in the end, a rational treatment plan. The addition of clinical information dramatically increases the likelihood of a meaningful and accurate pathologic diagnosis, especially in the setting of biopsies for diffuse lung disease (interstitial lung disease).

Parkinson’s disease (PD) is a neurodegenerative motor disorder that can associate with deficits in cognitive and emotional processing. In particular, PD has been reported to be mainly associated with defects in executive control and orienting attentional systems. The deficit in emotional processing mainly emerged in facial expression recognition. It is possible that the defects in emotional processing in PD may be secondary to other cognitive impairments, such as attentional deficits. This study was designed to systematically investigate the different weight of automatic and controlled attentional orienting mechanisms implied in emotional selective attention in PD. To address our purpose, we assessed drug-naïve PD patients and age-matched healthy controls with two dot-probe tasks that differed for stimuli duration. Automatic and controlled attentions were evaluated with stimuli lasting 100 ms and 500 ms, respectively. Furthermore, we introduced an emotion recognition task to investigate the performance in explicit emotion classification. The stimuli used in both the tasks dot-probe and emotion recognition were expressive faces displaying neutral, disgusted, fearful, and happy expressions.Our results showed that in PD patients, compared with healthy controls, there was 1) an alteration of automatic and controlled attentional orienting toward emotional faces in both the dot-probe tasks (with short and long durations), and 2) no difference in the emotion recognition task. These findings suggest that, from the early stages of the disease, PD can yield specific deficits in implicit emotion processing task (i.e., dot-probe task) despite a normal performance in explicit tasks that demand overt emotion recognition.

Background: Neuroinflammation is a key component in the etiopathogenesis of neurological diseases and brain aging. This process involves the brain immune system that modulates synaptic functions and protects neurons from infection or damage. Hence, the knowledge of neuroinflammation related-pathways and modulation by drugs or natural compounds is functional to the development of therapeutic strategies aimed at preserving, maintaining and restoring brain health. Objective: This review article summarizes the basics in neuroinflammation and related signaling pathways, the success of dietary intervention in clinical practice and the possible development of RNA-based strategies for the treatment of neurological diseases. Methods: Pubmed search (2012-2022); keywords: neuroinflammation and molecular mechanisms in combination with diet, miRNA and non-coding RNA. Results: Glial cells play a crucial role in neuroinflammation, but several pathways can be activated in response to different inflammatory stimuli, inducing cell death by apoptosis, pyroptosis or necroptosis. Dietary intervention has immunomodulatory effects and could limit the inflammatory process induced by microglia and astrocytes. Thus by ihibiting neuroinflammation and improving the symptoms of a variety of neurological diseases, diet exerts pleiotropic neuroprotective effects independently from the spectrum of pathophysiological mechanisms underlying the specific disorder. Furthermore, data from animal models revealed that altered expression of specific non-coding RNAs, in particular microRNAs, contributes to neuroinflammatory diseases; consequently, RNA-based strategies may be promising to alleviate the consequences of neuroinflammation. Conclusion: Further studies are needed to identify the molecular pathways and the new pharmacological targets in neuroinflammation to lay the basis for more effective and selective therapies to be applied, in parallel to dietary intervention, in the treatment of neuroinflammation-based diseases.

Background The role of video-assisted thoracoscopic segmentectomy in the treatment of clinical IA non-small-cell lung cancer is not well established. The aim of our retrospective analysis was to evaluate the oncological results of complex and simple video-assisted thoracoscopic segmentectomy. Methods From 2015 to June 2020, data of n = 163 consecutive patients undergoing video-assisted thoracoscopic segmentectomy for solitary pulmonary nodule were analysed. The Kaplan–Meier method, log-rank test and Cox regression were used to estimate, compare survivals and identify risk factors of worse oncological outcomes. Results In this period, n = 123 patients underwent video-assisted thoracoscopic segmentectomy for non-small-cell lung cancer: we performed n = 65 simple and n = 58 complex video-assisted thoracoscopic segmentectomy; n = 99 (80.5%) had a solid appearance on computed tomography scan and n = 78 (63.4%) a moderate-to-high [18F]-2-fluoro-2-deoxy-D-glucose (FDG)-positron emission tomographic computed tomography scan avidity. Mortality was 0%, and complications occurred in n = 14 (21.5%) and 9 (15.5%) patients. The median follow-up was 24 (range: 6−60) months and the 5-year overall survival was 96% without difference between video-assisted thoracoscopic segmentectomies ( p = 0.16). Local recurrence developed in n = 2 (3.1%) and n = 3 (5.2%) patients; regional in n = 2 (3.1%) and 1 (1.8%) and distant in 8 (12.3%) and 2 (3.4%), without difference between video-assisted thoracoscopic segmentectomies ( p = 0.51). The overall 5-year disease-free survival rate was 78%. Pathological upstaging was observed in n = 13 patients (nodal in n = 6, tumour in n = 7) and it was the only significant factor for worse disease-free survival at the multivariable analysis (hazard ratio: 2.43, 95% CI: 1.04−8.68, p = 0.049), value confirmed also in the group of intended video-assisted thoracoscopic segmentectomy ( p = 0.047). Conclusions Pathological upstaging after simple or complex video-assisted thoracoscopic segmentectomy is a risk factor for recurrence and then video-assisted thoracoscopic segmentectomy should be considered an appropriate therapeutic option for selected stage IA non-small-cell lung cancer patients.

To assess whether the incidence and aggressiveness of molar pregnancy (MP) and postmolar gestational trophoblastic neoplasia (GTN) changed during the COVID-19 pandemic.Observational study with two separate designs: retrospective multicentre cohort of patients with MP/postmolar GTN and a cross-sectional analysis, with application of a questionnaire.Six Brazilian Reference Centres on gestational trophoblastic disease.2662 patients with MP/postmolar GTN treated from March-December/2015-2020 were retrospectively evaluated and 528 of these patients answered a questionnaire.Longitudinal retrospective multicentre study of patients diagnosed with MP/ postmolar GTN at presentation and a cross-sectional analysis, with application of a questionnaire, exclusive to patients treated during the period of study, to assess living and health conditions during the COVID-19 pandemic compared with previous years.The incidence of MP/postmolar GTN.Compared with the last 5 pre-pandemic years, MP/postmolar GTN incidence remained stable during 2020 (COVID-19 pandemic). Multivariable logistic regression, adjusted for the patient age, showed that during 2020, presentation with MP was more likely to be10 weeks of gestation (adjusted odds ratio [aOR] 2.50, 95% confidence interval [CI] 1.90-3.29, P 0.001), have a pre-evacuation hCG level ≥100 000 iu/l (aOR 1.77, 95% CI 1.38-2.28, P 0.001) and time to the initiation of chemotherapy ≥7 months (aOR 1.86, 95% CI 1.01-3.43, P = 0.047) when compared with 2015-2019.Although the incidence of MP/postmolar GTN remained stable during the COVID-19 pandemic in Brazil, the pandemic was associated with greater gestational age at MP diagnosis and more protracted delays in initiation of chemotherapy for postmolar GTN.

A doença ulcerosa péptica atinge cerca de 10% da população global e possui uma incidência anual de 0,1%-0,3%, com prevalência ao longo da vida chegando a 5%-10%. Os principais fatores de risco, apontados como etiologia da doença, são o uso abusivo e contínuo de anti-inflamatórios não esteroides (AINEs) e a infecção do trato gastrointestinal (TGI) pelo Helicobacter Pylori (HP). Em relação à fisiopatologia, o uso de AINEs está associado ao desenvolvimento de úlcera péptica devido à inibição da enzima COX-1 por estes fármacos, a qual é responsável pela produção basal de prostaglandinas, que são responsáveis pelo estímulo à produção de muco sobre a mucosa do TGI. Nesse sentido, a redução da produção de prostaglandinas resulta em queda da formação da barreira fisiológica do organismo frente ao ácido clorídrico, o que propicia a atuação do mesmo sobre o epitélio intestinal, predispondo-o à erosão e formação de úlceras. Por outro lado, a fisiopatologia envolvida na infecção por HP ainda não foi em elucidada; entretanto, acredita-se que a formação de úlceras estejam correlacionadas, principalmente devido ao quadro inflamatório causado pela infecção bacteriana. Dessa forma, o presente artigo objetiva reunir informações na literatura a respeito dos principais conceitos relacionados à doença ulcerosa péptica, abordando aspectos como epidemiologia, etiofisiopatologia, diagnóstico e tratamento.

In routine clinical practice, contrast-enhanced mammography (CEM) examinations identify enhancing findings seen only on subtraction images that have no low-energy mammographic or sonographic correlate. The purpose of this study is to report the frequency and malignancy rates of enhancing findings seen only on subtraction images in a tertiary care breast imaging practice.Consecutive review of CEM exams from December 2015 to May 2020. Chi square tests were used to determine associations between cancer diagnosis and clinical characteristics of enhancing findings seen only on subtraction images, P .05 indicating a statistically significant difference.Four percent (100/2464) of CEM examinations identified 108 enhancing findings seen only on subtraction images. Twenty of those CEM enhancing findings were directly managed as a multifocal disease. Of those further evaluated with MR, 23% (19/78) with associated MR correlates were treated surgically as presumed multicentric or multifocal disease following multidisciplinary review. The remaining 76% (59/78) of enhancing findings were seen only on subtraction images, these included: 20% (12/59) and downgraded to benign on MR 80% (47/59) with suspicious findings which underwent MR vacuum assisted breast biopsy yielding: 26% (12/47) malignancy, 9% (4/47) high risk, and 66% (31/47) benign diagnoses.Enhancing findings seen on subtraction only CEM images are seen in 4% of cases in clinical practice. MR correlation can help characterize CEM findings to: (1) avoid unnecessary biopsy for benign findings, and (2) guide tissue sampling or empiric surgical planning for suspicious findings.

Giacomo Boscia,1,&ast; Pasquale Viggiano,1,&ast; Federica Marzulli,1 Maria Oliva Grassi,1 Pasquale Puzo,1 Stefano Dore,2 Antonio Pinna,2 Giovanni Alessio,1 Francesco Boscia1 1Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Bari, Italy; 2Department of Medicine, Surgery and Pharmacy, University of Sassari, Sassari, Italy&ast;These authors contributed equally to this workCorrespondence: Pasquale Viggiano, Department of Translational Biomedicine Neuroscience, University of Bari “Aldo Moro”, Piazza Giulio Cesare, 11, Bari, Italy, Tel +390805593728, Email pasquale.viggiano90@gmail.comPurpose: To assess the long-term morpho-functional retinal and choroidal changes in chronic central serous chorioretinopathy (cCSC) pachychoroid eyes in response to continuous oral eplerenone (EPL) treatment.Methods: This pilot study was conducted on patients with unilateral exudative cCSC. We enrolled a total of 17 exudative cCSC and 17 non-exudative fellow eyes of 17 patients. Baseline best-corrected visual acuity (BCVA) and anatomical (structural optical coherence tomography [OCT] and OCT angiography) parameters in both eyes were collected at baseline. Follow-up data were collected at 6, 12, and 48 months after initiation of EPL treatment.Results: (i) Exudative cCSC eyes: Compared with baseline (0.34± 0.13 LogMAR), BCVA significantly improved at follow-up examinations (6 months: 0.28± 0.13 LogMAR, p=0.039; 12 months: 0.22± 0.11 LogMAR, p=0.025; 48 months: 0.21± 0.08 LogMAR, p=0.028). Furthermore, there was a significant reduction from baseline in all structural OCT parameters (subretinal fluid and subfoveal choroidal thickness [SFCT]; p< 0.05). (ii) Non-exudative fellow eyes: There was no significant change in BCVA. There was a significant reduction from baseline in SFCT and choriocapillaris flow deficit percentage (p< 0.05).Conclusion: In this pilot study, continuous oral EPL therapy in cCSC pachychoroid eyes resulted in long-term morpho-functional improvement. The beneficial effect of EPL occurred within the first year and was maintained after four years. Based on these preliminary observations, EPL may be effective in the exudative forms of CSC.Keywords: central serous chorioretinopathy, choriocapillaris reperfusion, OCT and OCTA

Dystrophinopathies are X-linked recessive muscle disorders caused by mutations in the dystrophin (DMD) gene that include deletions, duplications, and point mutations. Correct diagnosis is important for providing adequate patient care and family planning, especially at this time when mutation-specific therapies are available. We report a large single-centre study on the spectrum of DMD gene variants observed in 750 patients analyzed for suspected Duchenne (DMD) or Becker (BMD) muscular dystrophy, over the past 30 years, at the Cardiomyology and Medical Genetics of the University of Campania. We found 534 (71.21%) large deletions, 73 (9.73%) large duplications, and 112 (14.93%) point mutations, of which 44 (5.9%) were small ins/del causing frame-shifts, 57 (7.6%) nonsense mutations, 8 (1.1%) splice site and 3 (0.4%) intronic mutations, and 31 (4.13%) non mutations. Moreover, we report the prevalence of the different types of mutations in patients with DMD and BMD according to their decade of birth, from 1930 to 2020, and correlate the data to the different techniques used over the years. In the most recent decades, we observed an apparent increase in the prevalence of point mutations, probably due to the use of Next-Generation Sequencing (NGS). In conclusion, in southern Italy, deletions are the most frequent variation observed in DMD and BMD patients followed by point mutations and duplications, as elsewhere in the world. NGS was useful to identify point mutations in cases of strong suspicion of DMD/BMD negative on deletions/duplications analyses. In the era of personalized medicine and availability of new causative therapies, a collective effort is necessary to enable DMD and BMD patients to have timely genetic diagnoses and avoid late implementation of standard of care and late initiation of appropriate treatment.

Immediate pigment darkening, the first response of skin to solar exposure leading to undesired irregular pigmentation and dark spots, is the rapid onset of melanin pigmentation resulting from oxidation of the melanogenic indoles, namely 5,6-dihydroxyindole (DHI) and 5,6-dihydroxyindole-2-carboxylic acid (DHICA) available in epidermal melanocytes. The search for effective sunscreen formulations is nowadays focused on UVA/B filters and additional ingredients that may scavenge the reactive oxygen species generated in these processes. In this work the effects of phenolic cosmetic ingredients (CIs), paradol-6, a ginger CO2 extract, and phenylethyl resorcinol on photosensitized DHI and DHICA oxidation were investigated showing a decrease of their consumption and melanin formation (25–30% decrease with phenylethyl resorcinol). The photoprotective role of CIs was also evaluated in model systems. Paradol-6 and ginger CO2 extract can halve linoleic acid peroxidation in the riboflavin-sensitized reaction, while dienes generation reduction (30% of control) was observed in the Rose-Bengal-sensitized photooxidation with paradol-6. The presence of DHI/DHICA melanin exerted a synergistic effect. The decay of thymine free or as a DNA base was almost completely inhibited by CIs. These results open new perspectives in the design of skin care formulations for ameliorating skin spots and contrasting ageing processes associated with sun exposure.

The kinetics of electron attachment to pyruvic acid (CH

En el presente artículo se busca demostrar que para llevar adelante políticas exteriores emancipatorias, es necesario contar con un cuerpo diplomático consciente de la opresión generada por el orden de género establecido. Así, se parte de afirmar que la potencialidad del personal diplomático, en ese sentido, no ha sido suficientemente explorada y analizada debido a que pertenece a estructuras estatales que son, por lo general, opresivas. Por ese motivo, se construyó el marco teórico a partir de conceptos elaborados por autoras como Alda Facio (metodologías feministas en lo legal), Silvina Álvarez (autonomía relacional), Miranda Fricker (injusticia epistémica), Nancy Fraser (reconocimiento como status) y Diana Maffía (redes de exclusión), entre otras, a fin de describir los procesos de invisibilización y la falta de reconocimiento y de opciones relevantes, como así también la creación de espacios epistémicos negativos que afectan a las mujeres y diversidades diplomáticas en sus trayectorias. Por último, se destaca la posibilidad que abre el status de outsider within, para repensar tanto el Estado como las relaciones de dominación existentes en el sistema internacional.

To characterize structural and clinical alterations preceding the diffuse macular atrophy in extensive macular atrophy with pseudodrusen (EMAP) and their evolution toward atrophic changes.A retrospective chart review was performed of patients with early-onset reticular pseudodrusen (i.e., pre-EMAP) younger than 55 years and EMAP with foveal sparing. Patients were included if they had complete medical records and multimodal imaging.A total of 12 patients were reviewed, of whom 4 of 12 patients (7 eyes) presented a pre-EMAP stage, characterized by the presence of pseudodrusen-like deposits without atrophic changes, while the remaining 8 of 12 patients (10 eyes) exhibited EMAP with foveal sparing (60.1 ± 6.4 years). Subretinal deposits of various stages tended to fade, leaving subretinal pigment epithelium accumulation of hyperreflective material with a physical separation between the retinal pigment epithelium-basal lamina and the Bruch membrane, along with the persistence of hyperreflective material after retinal pigment epithelium loss. These findings preceded atrophy development in a pre-EMAP stage and the EMAP stage with foveal sparing.Our findings presented distinct multimodal imaging features in eyes with reticular pseudodrusen depicting a peculiar phenotype of rapidly progressing atrophy in midlife. The disease spectrum may include other forms of geographic atrophy allied by thickened basal laminar deposits.

Chronic kidney disease (CKD) perturbs the crosstalk with others organs, with the interaction between the kidneys and the heart having been studied most intensively. However, a growing body of data indicates that there is an association between kidney dysfunction and disorders of the central nervous system. In epidemiological studies, CKD is associated with a high prevalence of neurological complications, such as cerebrovascular disorders, movement disorders, cognitive impairment and depression. Along with traditional cardiovascular risk factors (such as diabetes, inflammation, hypertension and dyslipidaemia), non-traditional risk factors related to kidney damage (such as uraemic toxins) may predispose patients with CKD to neurological disorders. There is increasing evidence to show that uraemic toxins, for example indoxyl sulphate, have a neurotoxic effect. A better understanding of factors responsible for the elevated prevalence of neurological disorders among patients with CKD might facilitate the development of novel treatments. Here, we review (i) the potential clinical impact of CKD on cerebrovascular and neurological complications, (ii) the mechanisms underlying the uraemic toxins’ putative action (based on pre-clinical and clinical research) and (iii) the potential impact of these findings on patient care., Graphical Abstract Graphical Abstract

Shelters are stressful environments for domestic dogs (Canis familiaris). Evaluating dogs’ welfare is crucial to improve their life condition and to promote a better management of shelters. We aimed at verifying which variables improved welfare in 10 shelter dogs ((hosted in the shelter “Centro cinofilo Caerite” in Bracciano (Rome)) by analysing their behavioural responses in different environmental conditions. Furthermore, faecal samples were taken to measure cortisol metabolites (CM), a non-invasive method to evaluate adrenocortical activity in dogs. Dogs were observed for a total of 400 h in 4 different cage conditions: (i) alone in a cage; ii) alone in an enriched cage; (iii) in cage with conspecifics; (iv) in cage with regular interaction with humans outside the cage. Alone in the cage situation showed highest frequencies of displacement activities (Friedman test: χ2 = 13.32; p = 0.004). In contrast, being in the cage with conspecifics seems to reduce displacement activity frequency, as well as the level of faecal cortisol metabolites (Friedman test: χ2 = 8.04; p = 0.045). Our results suggest that conspecifics’ presence is the best way to reduce stress in shelter dogs. This research could provide some useful guidelines for managing shelters and improving dogs’ life condition.

Lipofibromatous hamartoma (LFH) is a rare fibrofatty tumor of adipocytes within peripheral nerves, affecting mainly children. It typically presents as a palpable mass surrounding the nerves of the upper limbs, causing pain and neurological deficits in the affected nerve distribution. We report the case of a child with a 2-years presentation of a mass in the right wrist associated with pain and paresthesia, who underwent investigation with magnetic resonance imaging (MR I). It showed thickening of the median nerve with spaghetti-like appearance associated with lipomatous tissue in a coaxial cable-like pattern, both features characteristic of LFH. This case illustrates the importance of MRI in the differential diagnosis of limb masses in the pediatric population.

(1) Background: The principal aim of our research was to explore the relationship between digital devices use and fine motor skills in children aged three to six years and to explore the effect of some socio-demographic factors. (2) Methods: we enrolled 185 children aged between three to six years. The parents of all the participants fulfilled a questionnaire to explore the digital device use, and their children performed a standardized test to assess fine motor skills (APCM-2). We performed the Spearman correlation test to explore the relationship between different variables. (3) Results: the children spent an average of 3.08 ± 2.30 h/day on digital devices. We did not find a significant association between the time of use of digital devices and fine motor skills (p = 0.640; r = −0.036). The youngest children experienced digital tools earlier than older ones (p < 0.001; r = 0.424) and they were also the ones who used digital tools more time afterwards (p = 0.012; −0.202). The children who had working parents spent more time on digital devices (p = 0.028; r = 0.164/p = 0.037; r = 0.154) and used digital devices earlier (p = 0.023; r = 0.171). (4) Conclusions: This data suggest that it would be useful to monitor the use of digital tools, especially in the very first years of life. Future studies are needed to further explore this topic.

This study aimed to estimate the risks of adverse infant outcomes in the first year of life related to prenatal Zika virus (ZIKV) exposure. A prospective cohort of pregnant women with rash was recruited in Central-West Brazil in a post-epidemic period (January 2017 to April 2019). We evaluated participants’ medical histories and performed ZIKV diagnostic testing using molecular (reverse transcription polymerase chain reaction [RT-PCR]) and serologic (immunoglobulin [Ig]M and plaque reduction neutralization tests [PRNT90]) assays. The ZIKV-positive group included both RT-PCR-confirmed cases as well as IgM and/or PRNT90-positive probable cases. Children were evaluated at birth and in the first 12 months of life. Transfontanellar ultrasound, central nervous system computed tomography, eye fundoscopy and retinography were performed. We estimated the absolute risk and 95% confidence interval (95% CI) of adverse infant outcomes among confirmed prenatally ZIKV-exposed children. Among 81 pregnant women with rash, 43 (53.1%) were ZIKV infected. The absolute risk of microcephaly among offspring of ZIKV-infected pregnant women was 7.0% (95% CI: 1.5–19.1), including the two cases of microcephaly detected prenatally and one detected postnatally. In total, 54.5% (95% CI: 39.8–68.7) of children in the ZIKV-exposed group had at least one ophthalmic abnormality, with the most frequent abnormalities being focal pigmentary mottling and chorioretinal atrophy or scarring. Our findings reinforce the importance of long-term monitoring of prenatally ZIKV-exposed children born apparently asymptomatic for Congenital Zika Syndrome.

While the dissociative recombination (DR) of ground-state molecular ions with low-energy free electrons is generally known to be exothermic, it has been predicted to be endothermic for a class of transition-metal oxide ions. To understand this unusual case, the electron recombination of titanium oxide ions (TiO+) with electrons has been experimentally investigated using the Cryogenic Storage Ring. In its low radiation field, the TiO+ ions relax internally to low rotational excitation (≲100 K). Under controlled collision energies down to [Formula: see text] meV within the merged electron and ion beam configuration, fragment imaging has been applied to determine the kinetic energy released to Ti and O neutral reaction products. Detailed analysis of the fragment imaging data considering the reactant and product excitation channels reveals an endothermicity for the TiO+ dissociative electron recombination of (+4 ± 10) meV. This result improves the accuracy of the energy balance by a factor of 7 compared to that found indirectly from hitherto known molecular properties. Conversely, the present endothermicity yields improved dissociation energy values for D0(TiO) = (6.824 ± 0.010) eV and D0(TiO+) = (6.832 ± 0.010) eV. All thermochemistry values were compared to new coupled-cluster calculations and found to be in good agreement. Moreover, absolute rate coefficients for the electron recombination of rotationally relaxed ions have been measured, yielding an upper limit of 1 × 10−7 cm3 s−1 for typical conditions of cold astrophysical media. Strong variation of the DR rate with the TiO+ internal excitation is predicted. Furthermore, potential energy curves for TiO+ and TiO have been calculated using a multi-reference configuration interaction method to constrain quantum-dynamical paths driving the observed TiO+ electron recombination.

Enteroliths are intraluminal calculi formed in the small bowel, commonly caused by chronic intestinal constipation associated with other comorbidities. We describe an atypical case of enterolithiasis diagnosed with computed tomography scan (CT) and which was confirmed during subsequent surgical resection. A 66-year-old female patient had a history of chronic constipation and use of laxatives and presented with abdominal pain. A CT scan showed heterogeneous annular formations with a hyperdense halo and a hypodense center within the loops of small bowel. A segment was resected for enterectomy, allowing several yellowish stony structures to be identified, corresponding to enteroliths.

Polyphenon E (Poly E) is a green tea polyphenol preparation whose most active component is epigallocatechin gallate (EGCG). We studied the cancer preventive efficacy and safety of Poly E in subjects with rectal aberrant crypt foci (ACF), which represent putative precursors of colorectal cancers. Eligible subjects had prior colorectal advanced adenomas or cancers, and had ≥5 rectal ACF at a preregistration chromoendoscopy. Subjects (N = 39) were randomized to 6 months of oral Poly E (780 mg EGCG) daily or placebo. Baseline characteristics were similar by treatment arm (all P >0.41); 32 of 39 (82%) subjects completed 6 months of treatment. The primary endpoint was percent reduction in rectal ACF at chromoendoscopy comparing before and after treatment. Among 32 subjects (15 Poly E, 17 placebo), percent change in rectal ACF number (baseline vs. 6 months) did not differ significantly between study arms (3.7% difference of means; P = 0.28); total ACF burden was also similar (−2.3% difference of means; P = 0.83). Adenoma recurrence rates at 6 months were similar by arm (P > 0.35). Total drug received did not differ significantly by study arm; 31 (79%) subjects received ≥70% of prescribed Poly E. Poly E was well tolerated and adverse events (AE) did not differ significantly by arm. One subject on placebo had two grade 3 AEs; one subject had grade 2 hepatic transaminase elevations attributed to treatment. In conclusion, Poly E for 6 months did not significantly reduce rectal ACF number relative to placebo. Poly E was well tolerated and without significant toxicity at the dose studied.Prevention Relevance:We report a chemoprevention trial of polyphenon E in subjects at high risk of colorectal cancer. The results show that polyphenon E was well tolerated, but did not significantly reduce the number of rectal aberrant crypt foci, a surrogate endpoint biomarker of colorectal cancer.

Supplementary Table 1

The aim of the study is to evaluate clinical applications, safety, and effectiveness of a porcine-derived acellular cross-linked dermal matrix biological mesh in chest wall reconstruction.We retrospectively analyzed a prospective multicenter database of chest wall reconstructions using a biological mesh in adult patients undergoing operation between October 2013 and December 2020. We evaluated preoperative data, type of resection and reconstruction, hospitalization, 30-day morbidity and mortality, and overall survival.A total of 105 patients (36 women [34.2%]; mean age, 57.0 ± 16.1 years; range, 18-90 years) were included, they have admitted for: primary chest wall tumor (n = 52; 49.5%), secondary chest wall tumor (n = 29; 27.6%), lung hernia (n = 12; 11.4%), trauma (n = 10; 9.6%), and infections (n = 2; 1.9%). The surgical sites were preoperatively defined as at high risk of infection in 28 patients (26.7%) or as infected in 16 (15.2%) patients. Thirty-days morbidity was 30.5% (n = 32 patients); 14 patients (13.3%) had postoperative complications directly related to chest wall surgical resection and/or reconstruction. We experienced no 30-day mortality; 1-year and 2-year mortality was 8.4% and 16.8%, respectively.Biological mesh represents a valuable option in chest wall reconstruction even when surgical sites are infected or at high-risk of infections. This mesh shows low early and late postoperative complication rates and excellent long-term stability.

Introduction. Pituitary differentiation involves a large number of transcription factors. In particular, BMP4 expression is fundamental for pituitary gland commitment from the ventral diencephalon, suppressing Shh expression in Rathke’s pouch. Pathogenic variants in BMP4 are reported in the literature with a broad phenotypic spectrum, including pituitary and brain malformations. Case Presentation. A five-year-old girl came to medical attention following a mild cervical trauma with onset of cervical pain. On clinical examination at birth, postaxial polydactyly type B of the left hand was observed and removed at 10 months of age. A cervical radiography was performed, and a suspicion of craniocervical junction malformation was made. A magnetic resonance imaging of the cervical spine was made, showing an ectopic posterior pituitary, associated with dysmorphism of the craniocervical junction. The anthropometric parameters were pubertal Tanner stage 1, weight 16 kg (z-score: −1.09), height 107 cm (z-score: −0.76), and BMI 14 kg/m2 (z-score: −0.92). Normal hormonal assessment was detected. Genetic analysis via next generation sequencing showed a novel de novo heterozygous variant (c.277 G > T, p.Glu93 ∗ ) in exon 3 of BMP4. Discussion. We described a novel mutation in BMP4, resulting in ectopic posterior pituitary with normal hormonal assessment, associated to craniocervical junction dysmorphism and limb anomaly. It is important to monitor patient’s growth and puberty and to screen the onset of symptoms related to the deficiency of one or more anterior as well as posterior pituitary hormones.

To investigate choroidal vascularity index (CVI) changes after oral eplerenone treatment in chronic central serous chorioretinopathy (cCSC) using the Spectral-domain (SD)-Optical Coherence Tomography (OCT) with enhanced depth imaging (EDI) mode.Thirty-six eyes of 18 patients suffering from cCSC with monolateral foveal subretinal fluid (FSRF) successfully treated with oral eplerenone treatment and 18 age-matched healthy subjects were enroled in this retrospective study. EDI-OCT images obtained using Heidelberg Spectralis OCT device in patients with cCSC and FSRF (group 1); fellow eye (group 2) or healthy patients (healthy) were exported and then imported into image analysis ImageJ software for subsequent quantitative analysis. The main outcome measures were luminal area (LA) and CVI.A higher value of CVI was detected in group 1 compared to healthy eyes (p = 0.006). LA and CVI significantly reduced during follow up in group 1 and group 2. LA at 120 days was significantly lower compared to all previous time points both in group 1 and group 2 (p 0.001). Median and [1st -3rd quartile] CVI values were 0.8 [0.7; 1.1] at baseline, 0.8 [0.7; 0.9] at 30 days; 0.7 [0.6; 0.9] at 60 and 90 days and 0.6 [0.5; 0.8] at 120 days in group 1 (p = 0.007) and 0.7 [0.6; 0.9] at baseline, 0.7 [0.7; 0.8] at 30 days; 0.7 [0.6; 0.7] at 60 and 90 days and 0.6 [0.6; 0.7] at 120 days in group 2 (p = 0.018).Choroidal vascularity index reduced in cCSC patients after oral eplerenone treatment during follow up both in eyes with SRF and fellow eyes thus demonstrating the effectiveness of mineral corticoid receptor antagonists in recovering choroidal morphology.

The contribution of brain regions to visuospatial abilities according to sex differences and gender identity is inconsistently described. One potential explaining factor may be the different tasks employed requiring a variable load of working memory and other cognitive resources. Here we asked to 20 cis and 20 transgender participants to undergo functional Magnetic Resonance Imaging during performance of a judgement line of orientation test that was adapted to explore the basic visuospatial processing while minimizing the working memory load. We show that V1 activation may be viewed as a brain area with enhanced activation in males, regardless of participants’ gender identity. On its turn, gender identity exclusively influences the visuospatial processing of extrastriate visual areas (V5) in women with gender dysphoria. They showed enhanced V5 activation and an increased functional connectivity between V5 and V1. Overall our neuroimaging results suggest that the basic visuospatial abilities are associated with different activations pattern of cortical visual areas depending on the sex assigned at birth and gender identity.

The objective of our study was to evaluate the impact of the COVID-19 pandemic on the emotional and behavioral symptoms in minors with neuropsychiatric disorders and on parental stress through a standardized neuropsychological assessment, comparing the data collected before the pandemic with those collected during the lock-down. Another goal of our study was to analyze the relationship between parental stress and behavioral/emotional symptoms in children. Our study was conducted on 383 families of patients who had already been referred at the Child Neuropsychiatry Unit of the University Hospital of Salerno for different neuropsychiatric conditions. All the parents completed two neuropsychological standardized questionnaires for the assessment of parental stress (PSI—Parenting Stress Index-Short Form) and the emotional/behavioral problems of their children (Child Behaviour CheckList). The data collected during the pandemic were compared with those collected from questionnaires administered during the six months preceding the pandemic, as is our usual clinical practice. The comparison between the mean scores of PSI and CBCL before and after the pandemic showed a statistically significant increase in all subscales analyzed in the total sample. The correlation analysis showed significant positive relationship between the subscale Total Stress of PSI and the subscales Total Problems and Internalizing Problems of CBCL. Our study suggested that the COVID-19 pandemic and the corresponding measures adopted led to an increase in internalizing and externalizing symptoms in children and adolescents with neuropsychiatric disorder. Similarly, parental stress increased during COVID-19 and ahigher level of stress in parents can be related to the internalizing symptoms of their children.

Neurocognitive disorders are frequent among chronic kidney disease (CKD) patients. Identifying and characterizing cognitive impairment (CI) can help to assess the ability of adherence to CKD risk reduction strategy, identify potentially reversible causes of cognitive decline, modify pharmacotherapy, educate the patient and caregiver and provide appropriate patient and caregiver support. Numerous factors are associated with the development and progression of CI in CKD patients and various conditions can influence the results of cognitive assessment in these patients. Here we review clinical warning signs that should lead to cognitive screening; conditions frequent in CKD at risk to interfere with cognitive testing or performance, including specificities of cognitive assessment in dialysis patients or after kidney transplantation; and available tests for screening and observed cognitive patterns in CKD patients., Graphical Abstract Graphical abstract

Funding: This article is published as part of a supplement financially supported by the COST Action CA19127-Cognitive Decline in Nephro-Neurology: European Cooperative Target (CONNECT). Kidney function has two important elements: glomerular filtration and tubular function (secretion and reabsorption). A persistent decrease in glomerular filtration rate (GFR), with or without proteinuria, is diagnostic of chronic kidney disease (CKD). While glomerular injury or disease is a major cause of CKD and usually associated with proteinuria, predominant tubular injury, with or without tubulointerstitial disease, is typically non-proteinuric. CKD has been linked with cognitive impairment, but it is unclear how much this depends on a decreased GFR, altered tubular function or the presence of proteinuria. Since CKD is often accompanied by tubular and interstitial dysfunction, we explore here for the first time the potential role of the tubular and tubulointerstitial compartments in cognitive dysfunction. To help address this issue we selected a group of primary tubular diseases with preserved GFR in which to review the evidence for any association with brain dysfunction. Cognition, mood, neurosensory and motor disturbances are not well characterized in tubular diseases, possibly because they are subclinical and less prominent than other clinical manifestations. The available literature suggests that brain dysfunction in tubular and tubulointerstitial diseases is usually mild and is more often seen in disorders of water handling. Brain dysfunction may occur when severe electrolyte and water disorders in young children persist over a long period of time before the diagnosis is made. We have chosen Bartter and Gitelman syndromes and nephrogenic diabetes insipidus as examples to highlight this topic. We discuss current published findings, some unanswered questions and propose topics for future research. publishersversion published

Major associations of medical oncologists remark that novel anticancer treatments should guarantee improvement of survival outcomes as well as of patients' quality of life (QoL). Herein, we investigated QoL assessment and reporting in phase III randomized controlled trials (RCTs) testing new drugs in metastatic non-small cell lung cancer (NSCLC), published between 2010 and 2021. We selected 172 RCTs for further analysis. Only 2/172 (1.2%) trial included QoL among primary study endpoints. Of note, 40/172 (23.3%) trials did not include QoL assessment among endpoints. The majority of RCTs (102/172, 59.3%) did not report QoL results in primary publications. Particularly, RCTs testing immunotherapy, target therapy and chemotherapy did not disclose QoL data in primary publications in 97.0%, 51.5% and 46.5% of cases, respectively. Next, we found that only 43/95 (45.3%) positive studies reported QoL results in primary articles. Of the 102 trials missing QoL data in primary manuscripts, only 21 (20.6%) disclosed QoL results in a secondary publication. Finally, we found a common fail in adherence to CONSORT-PROs items in publications reporting QoL results. In summary, our study reveals a relevant inadequate assessment and under-reporting of QoL in RCTs of novel systemic treatments for patients with metastatic NSCLC.

La partecipazione sociale e politica digitale contemporanea (e-Democracy) è un prodotto della digitalizzazione dello Stato e dei suoi apparati, caratterizzata dalla produzione di nuovi diritti resi possibili dalle tecnologie della comunicazione. La digitalizzazione degli apparati dello Stato attraverso le nuove tecnologie basate su algoritmi intelligenti e le norme sulla società dell’informazione e della comunicazione hanno innescato la produzione di cosiddetti “nuovi diritti” la cui esigibilità amplia il concetto di democrazia stabilendo una differenza tra il tradizionale governo della cosa pubblica e le crescenti pretese delle comunità sempre più legate al sistema della comunicazione digitale. I diritti di accedere a Internet e alla rete, all’e-voting, a comunicare con la PA attraverso le nuove tecnologie, a ricevere servizi pubblici digitali sono paralleli a doveri dello Stato caratterizzati dalla soddisfazione dei nuovi diritti. Contemporaneamente cresce il rischio che forme di partecipazione digitale producano livelli di esclusioni intollerabili che intaccano la democrazia. Osservare e descrivere, con gli strumenti concettuali del Centro di Studi sul Rischio, come il sistema del diritto, della politica e della società evolvono attraverso il rapporto con l’ecosistema digitale trainato dall’arcipelago delle intelligenze artificiali rappresenta l’obiettivo e la sfida sempre incerta negli esiti, sempre nuova nelle acquisizioni ma sempre stimolante e proficua sotto il profilo della ricerca sociale, politica e giuridica.