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Biotechnology has become one of the most powerful forces on the planet, since it is capable of altering life processes at a molecular level. Since human bodies are dynamic biological systems, medicine requires to understand the evolutionary antecedents of Homo, especially in relation to neurohormonal regulation. Furthermore, increasing human dependence on biotechnology has led to relaxed natural selection in Homo, with subsequent increase of genetic load. In this paper, we speculate on the possible consequences of the application of parsimoniously derived biotechnologies onto the biological system of humans, with special attention to three areas: 1. human brain augmentation; 2. biotechnology and public health; 3. relaxed natural selection and genetic load. Human ability to manipulate and alter the structure and function of the body may not only make natural selection redundant but will be guided by a teleology whose purpose will seek to improve upon nature’s design.

This article summarises the main findings and data on the ancient peopling of the Mediterranean island of Sicily through an archaeo-anthropological perspective. The hypothesis surrounding the presence of the Lower Palaeolithic in Sicily with more ancestral species of Homo is also extensively reviewed and it is explained why there are not sufficient elements to maintain it. Finally, future multidisciplinary proposals are made to fill the gap on Sicilian cave archaeology.

Abstract Acute promyelocytic leukemia (APL) is characterized by rearrangements of the retinoic acid receptor, RARα, which makes all-trans retinoic acid (ATRA) highly effective in the treatment of this disease, inducing promyelocytes differentiation. Current therapy, based on ATRA in combination with arsenic trioxide, with or without chemotherapy, provides high rates of event-free survival and overall survival. However, a decline in the drug activity, due to increased ATRA metabolism and RARα mutations, is often observed over long-term treatments. Furthermore, dedifferentiation can occur providing relapse of the disease. In this study we evaluated fenretinide, a semisynthetic ATRA derivative, encapsulated in nanomicelles (nano-fenretinide) as an alternative treatment to ATRA in APL. Nano-fenretinide was prepared by fenretinide encapsulation in a self-assembling phospholipid mixture. Physico-chemical characterization was carried out by dinamic light scattering and spectrophotometry. The biological activity was evaluated by MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Nano-fenretinide induced apoptosis in acute promyelocytic leukemia cells (HL60) by an early increase of reactive oxygen species and a mitochondrial potential decrease. The fenretinide concentration that induced 90–100% decrease in cell viability was about 2.0 µM at 24 h, a concentration easily achievable in vivo when nano-fenretinide is administered by oral or intravenous route, as demonstrated in previous studies. Nano-fenretinide was effective, albeit at slightly higher concentrations, also in doxorubicin-resistant HL60 cells, while a comparison with TK6 lymphoblasts indicated a lack of toxicity on normal cells. The results indicate that nano-fenretinide can be considered an alternative therapy to ATRA in acute promyelocytic leukemia when decreased efficacy, resistance or recurrence of disease emerge after protracted treatments with ATRA.

Abstract This paper investigates trabecular bone ontogenetic changes in two different Polish populations, one prehistoric and the other historical. The studied populations are from the Brześć Kujawski region in Kujawy (north-central Poland), one from the Neolithic Period (4500–4000 BC) and one from the Middle Ages (twelfth-sixteenth centuries AD), in total 62 vertebral specimens (32 males, 30 females). Eight morphometric parameters acquired from microCT scan images were analysed. Two-way ANOVA after Box-Cox transformation and multifactorial regression model were calculated. A significant decrease in percentage bone volume fraction (BV/TV; [%]) with age at death was observed in the studied sample; Tb.N (trabecular number) was also significantly decreased with age; trabecular separation (Tb.Sp) increased with advancing age; connectivity density (Conn.D) was negatively correlated with biological age and higher in the Neolithic population. These data are found to be compatible with data from the current biomedical literature, while no loss of horizontal trabeculae was recorded as would be expected based on modern osteoporosis.

Abstract Background Peritoneal metastases from colorectal cancer (CRCPM) are related to poor prognosis. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been reported to improve survival, but peritoneal recurrence rates are still high and there is no consensus on the drug of choice for HIPEC. The aim of this study was to use patient derived organoids (PDO) to build a relevant CRCPM model to improve HIPEC efficacy in a comprehensive bench-to-bedside strategy. Methods Oxaliplatin (L-OHP), cisplatin (CDDP), mitomycin-c (MMC) and doxorubicin (DOX) were used to mimic HIPEC on twelve PDO lines derived from twelve CRCPM patients, using clinically relevant concentrations. After chemotherapeutic interventions, cell viability was assessed with a luminescent assay, and the obtained dose–response curves were used to determine the half-maximal inhibitory concentrations. Also, induction of apoptosis by different HIPEC interventions on PDOs was studied by evaluating CASPASE3 cleavage. Results Response to drug treatments varied considerably among PDOs. The two schemes with better response at clinically relevant concentrations included MMC alone or combined with CDDP. L-OHP showed relative efficacy only when administered at low concentrations over a long perfusion period. PDOs showed that the short course/high dose L-OHP scheme did not appear to be an effective choice for HIPEC in CRCPM. HIPEC administered under hyperthermia conditions enhanced the effect of chemotherapy drugs against cancer cells, affecting PDO viability and apoptosis. Finally, PDO co-cultured with cancer-associated fibroblast impacted HIPEC treatments by increasing PDO viability and reducing CASPASES activity. Conclusions Our study suggests that PDOs could be a reliable in vitro model to evaluate HIPEC schemes at individual-patient level and to develop more effective treatment strategies for CRCPM.

ObjectiveMutations in the genes encoding neuronal ion channels are a common cause of Mendelian neurological diseases. We sought to identify novel de novo sequence variants in cases with early infantile epileptic phenotypes and neurodevelopmental anomalies.MethodsFollowing clinical diagnosis, we performed whole exome sequencing of the index cases and their parents. Identified channel variants were expressed in Xenopus oocytes and their functional properties assessed using two-electrode voltage clamp.ResultsWe identified novel de novo variants in KCNA6 in four unrelated individuals variably affected with neurodevelopmental disorders and seizures with onset in the first year of life. Three of the four identified mutations affect the pore-lining S6 α-helix of KV 1.6. A prominent finding of functional characterization in Xenopus oocytes was that the channel variants showed only minor effects on channel activation but slowed channel closure and shifted the voltage dependence of deactivation in a hyperpolarizing direction. Channels with a mutation affecting the S6 helix display dominant effects on channel deactivation when co-expressed with wild-type KV 1.6 or KV 1.1 subunits.SignificanceThis is the first report of de novo nonsynonymous variants in KCNA6 associated with neurological or any clinical features. Channel variants showed a consistent effect on channel deactivation, slowing the rate of channel closure following normal activation. This specific gain-of-function feature is likely to underlie the neurological phenotype in our patients. Our data highlight KCNA6 as a novel channelopathy gene associated with early infantile epileptic phenotypes and neurodevelopmental anomalies.

The present communication examines the phenomenon of curfew in relation to the COVID-19 pandemic with special attention being laid on the management of the epidemic by Italian health authorities. A literature review and a historical–medical analysis were performed. A historical–medical excursus on the word curfew is offered and a comparison between military and health scenarios is given. Finally, this article stresses how words connected with wartime events should be contextualized when adopted in unmilitary scenarios such as pandemic emergencies and related public health responses.

Background/aims: Myocarditis is an inflammatory disease with diverse clinical presentations. It is known that low-risk patients have a good prognosis compared to high-risk patients. There are few data regarding the prognosis of intermediate-risk patients. This study aimed to analyze the long-term outcomes of patients with acute myocarditis with different risk profiles at presentation, focusing on the intermediate risk one. Methods: A retrospective multicenter study was conducted, enrolling patients who met the diagnostic criteria for clinically suspected myocarditis with acute presentation. Patients were stratified into high, intermediate and low risk, according to the classification proposed by Sinagra and his team. Cardiovascular adverse events (AEs) were assessed after a median follow-up of 19 months. Echocardiographic and cardiac magnetic resonance (CMR) parameters predictive of adverse events have been reported. Results: We enrolled 127 patients (mean age 30 ± 13 years; 103 men, 24 women). High-risk patients had a higher frequency of adverse events (80 %) compared to other groups (16 %–16 %, p

Trata-se de um estudo transversal, descritivo e analítico que utilizou dados secundários da base de dados de vigilância epidemiológica de domínio público no Brasil, no período de dezembro de 2021 a julho de 2022. O objetivo do estudo foi analisar os casos de SRAG associada a covid-19 em gestantes que foram hospitalizadas em unidade de terapia intensiva (UTI) no Brasil. A amostra foi constituída por 239 gestantes que tiveram COVID-19 e foram internadas em UTI, sendo 205 com descrição do desfecho final e 34 sem desfecho final do caso. Para análise estatística, os dados foram importados para o programa R versão 4.2.0, 2022 e realizada a análise descritiva de prevalência, medidas de associação (razão de prevalência e diferença de prevalência). Em seguida calculou-se a prevalência de grávidas que foram internadas em UTI por unidade de federação (estado). Os estados que apresentaram maior prevalência de internamento em UTI foram Amapá, Tocantins e Paraná, os sintomas mais informados foram tosse e febre, obesidade, doenças cardiovasculares, diabetes, raça preta, idade materna avançada e terceiro trimestre gestacional estavam associados a hospitalização. Mesmo ocorrendo casos de internamento em UTI e óbitos, a maioria das pacientes com a doença apresentaram desfecho favoráveis, o que indica que a infecção não influenciou significativamente na gestação. No entanto, a falta de informações sobre a vacinação e as doses recebidas pelas gestantes não permitiu concluir a resposta imunológica da vacina nesta população.

We present a rare case of eosinophilic granulomatosis with polyangiitis (EGPA), involving a 26-year-old woman with a history of asthma and nasal polyps. The patient presented with acute aortoiliac thrombosis and mitral insufficiency, which was successfully treated with thrombolysis, aortic thromboendarterectomy, and valve replacement. Peripheral hypereosinophilia with eosinophilic infiltration of the heart led to the diagnosis of antineutrophilic cytoplasmic antibody–negative EGPA. Treatment with prednisone and mepolizumab was started, resulting in a positive outcome. This case showcases an unusual manifestation of EGPA with large size vessel involvement and requiring surgical and pharmacological treatment. It also highlights the importance of early detection for timely intervention and an improved prognosis.

Introduction: Since the beginning of the COronaVIrus Disease 2019 (COVID-19) pandemic, poor attention has been paid to the indirect effects of the pandemia on cardiovascular health system, in particular in patients with Acute Coronary Syndrome (ACS). The aims of this study is to compare possible epidemiological, clinical and management differences between the four epidemic waves in groups of patients hospitalized for ACS with a view to highlighting the burden of the pandemic on the management of this syndrome. Materials and methods: In this retrospective observational study we included 98 patients admitted to Coronary Intensive Care Unit (CICU) for ACS between March 2020 and March 2022, who underwent revascularization procedure using percutaneous coronary angioplasty (PCI). The patients examined were divided into four groups representative of the four epidemic waves that affected our country. Results: The rate of hospitalization for ACS increased progressively to a 178 % increase in the third wave compared to the first (p = 0.003), with an increase of 900 % if we consider only Non-ST-Elevation Myocardial Infarction (NSTEMI) (representing 54 % of the ACS diagnoses of the third group against 14.3 % in the first). Longer door-to-balloon times were recorded in the third wave for the increased presence of NSTEMI. The average hospital stay was lower in the third wave with 5 ± 2 days (p = 0.007) as well as mortality (5.1 % in the third wave; the highest in the fourth wave with 9.5 %). Conclusions: The study show that the management of ACS suffered most from the indirect effects of the pandemic during the first wave, both because of the unpreparedness of hospital facilities and because of the fear of infection that has dissuaded people from asking for help.

Abstract As known “ecosystem engineers”, beavers influence river hydrology, geomorphology, biochemistry, and biological assemblages. However, there is a lack of research regarding the effects of beaver activities on freshwater meiofauna. In this study, we investigated the taxonomic and functional composition of the benthic copepod assemblage of a segment of the Tiber River (Italy) where a beaver dam, created about 7 weeks before our survey, had formed a semi-lentic habitat upstream and a lotic habitat downstream of the dam. We also analyzed the copepod assemblage before and after a flood event that destroyed the beaver dam, providing a unique opportunity to observe changes in a naturally reversing scenario. Our analyses revealed that, while the taxonomic composition and functional traits of the copepod assemblage remained largely unchanged across the recently formed semi-lentic and lotic habitats, substantial differences were evident between the dammed and undammed states. The dammed state showed lower copepod abundances, biomass, and functionality than the undammed one. These results highlight the role of beaver dams in changing the composition and functionality of meiofaunal assemblages offering insights into the dynamic interactions within aquatic ecosystems.

Abstract Background Anthracyclines can cause left ventricular (LV) dysfunction. There is little data about right ventricular (RV) damage during chemotherapy. Aim This study aimed to investigate the toxic effects of chemotherapy, analyzing its impact on right ventricular function. Material and Methods A prospective study was conducted, enrolling 83 female patients (55 ± 11 years old) affected by breast cancer treated with anthracyclines. Cardiological evaluation, HFA risk score assessment and comprehensive echocardiogram, including speckle tracking analysis and 3D analysis, were performed before starting chemotherapy (T0) and at 3 (T1), 6 (T2) and 12 months (T3) after beginning treatment. RV function was assessed with tricuspid annular plane excursion (TAPSE), S’ wave of the tricuspid annulus, fractional area change (FAC), RV global longitudinal strain (RV-GLS), free wall strain (RV-FWLS) and RV 3D ejection fraction (RV-3DEF). Subclinical LV CTRCD was defined as a reduction of GLS > 15% compared to baseline. Subclinical RV cardiotoxicity was defined as the co-presence of a relative decrease of 10% from baseline in RV-3DEF and a relative reduction of 15% from baseline RV-FWLS. Results After chemotherapy, we found a significant reduction in 2D-LVEF (p =

Binder Jetting (BJT) is a non-fusion-based Additive Manufacturing (AM) technique. It consists of the selective deposition of a liquid binder to join powder particles, thereby enabling the creation of near-net-shaped parts.In this study, the main printing parameters correlated to the binder distribution and infiltration (binder saturation, binder set time, drying time, and target bed temperature) were optimised to improve the precision of green parts printed with potassium sodium niobate (KNN) powder. The optimisation procedure was conducted using the Taguchi statistical method. An L9 orthogonal array with four factors of control at three levels each was employed. The analysis showed that the drying time had the greatest influence on the precision of green parts, followed by binder saturation and target bed temperature. Binder set time did not seem to affect the results.Dimensional analysis, microstructural and piezoelectric characterisation of parts densified by pressureless sintering were conducted. The highest average relative density exceeded 80% for the specimens printed with the lower binder saturation. Piezoelectric properties exhibit more complex behaviour. The prolonged infiltration of larger binder volumes is correlated to higher g33, thus FOMh and FOM33, and lower values for ε33T. On the other hand, d33 does not display a specific dependence on density or printing parameters.The results of this study indicate that BJT can be used to fabricate high-precision KNN components with good piezoelectric properties. The optimisation of printing parameters is essential to achieve the desired results.

This work presents the results of a geomatic survey conducted on the Anatomical Machines within the Sansevero Chapel in Naples, Italy. These anatomical artifacts have the unique characteristics of being upright standing skeletons with nearly intact circulatory systems. Previous research revealed that the intricate vascular systems, once believed to be natural, are instead elaborate reconstructions made using materials such as beeswax and dyes.In response to the lack of metric data of these models, a series of geomatic surveys has been conducted to create the Machines’ 3D models. This study discusses the theoretical and practical challenges associated with surveying these complex and fragile artifacts, emphasising the need for accurate extraction techniques to overcome the limitations imposed by the wooden cases in which they are encased. Two distinct approaches were used: a photogrammetric reconstruction and a laser scanning survey to overcome some logistical difficulties encountered. Despite the challenges, the 3D models' analysis gave satisfactory results.This work addresses the palaeopathological and anatomical questions related to the Anatomical Machines by leveraging non-invasive geomatic methodologies, shedding light on the complexities of surveying historically significant artifacts and aiming at further establishing a valuable foundation for improving these modelling techniques.

Abstract Data standardization promotes a common framework through which researchers can utilize others’ data and is one of the leading methods neuroimaging researchers use to share and replicate findings. As of today, standardizing datasets requires technical expertise such as coding and knowledge of file formats. We present ezBIDS, a tool for converting neuroimaging data and associated metadata to the Brain Imaging Data Structure (BIDS) standard. ezBIDS contains four major features: (1) No installation or programming requirements. (2) Handling of both imaging and task events data and metadata. (3) Semi-automated inference and guidance for adherence to BIDS. (4) Multiple data management options: download BIDS data to local system, or transfer to OpenNeuro.org or to brainlife.io. In sum, ezBIDS requires neither coding proficiency nor knowledge of BIDS, and is the first BIDS tool to offer guided standardization, support for task events conversion, and interoperability with OpenNeuro.org and brainlife.io.

Background: The objective was to analyze the budgets invested in prisons by the member states of the Council of Europe (CoE) and the relationships between the global cost, the cost incurred per single inmate, the number of inmates per 100,000 inhabitants (PPR), the gross domestic product (GDP) and per capita GDP. Methods: The data relating to the variables considered for the year 2020 were obtained from the SPACE-I 2021 of the CoE, the World Bank/OECD, and Eurostat. Regression models were used to evaluate the relationships between the PPR and the GDP, the daily cost per prisoner and per capita GDP, and between the PPR and the per capita GDP. A multiple correspondence analysis was performed to evaluate associations between the PPR, EU membership, cost per day, cost rate, geographical area, and inmate gender. Results: The daily expenditure per inmate in northern European countries reaches very high values, respectively: EUR 330.6 (Norway) and EUR 303 (Sweden), while, in the eastern countries, the values drop sharply (EUR 6.50 in Bulgaria and EUR 8.08 in Azerbaijani). The lowest PPR values are found in northern European countries, and the highest in the following countries: Russia, Turkey, Georgia, and Azerbaijan. Conclusions: Countries with a higher GDP per capita tend to have lower prison population rates and to invest larger amounts of funds for prison systems.

Objective: Colon adenocarcinoma is characterized by the downregulation of the retinoic acid receptor, making natural retinoids such as all-trans retinoic acid, 9-cis retinoic acid and 13-cis retinoic acid effective in treatment and chemoprevention due to their ability to increase RARβ expression. However, major limitations to their use include tolerability and acquired resistance. In this study, we evaluated fenretinide, a semisynthetic derivative of all-trans retinoic acid, in an HT-29 cell line. Fenretinide was evaluated both as a free drug and encapsulated in self-assembling phosphatidylcholine nanosystems with the aim of increasing the aqueous solubility and cell availability of the drug. Methods: Fenretinide was encapsulated in lipid nanosystems obtained in water by the dispersion of an amphiphilic mixture of phospholipids, glyceryl tributyrate and polysorbate 80. The physico-chemical characterization of the nanosystems was carried out by dynamic light scattering and spectrophotometry. The biological activity was evaluated by quantitative phase imaging microscopy, MTT assay, flow cytometry and confocal laser-scanning fluorescence microscopy. Results: Fenretinide in phosphatidylcholine nanosystems was more active than free fenretinide in inhibiting HT-29 cells’ proliferation, as indicated by quantitative phase imaging data. Indeed, encapsulated fenretinide increased duplication time, decreased dry mass and decreased the rate of cell growth more efficiently than fenretinide. Moreover, encapsulated fenretinide effectively decreased the motility of the cells that survived the treatment. Conclusions: The results indicate that the proposed nanosystems can be considered a valuable alternative to natural retinoids in the chemoprevention and treatment of colorectal cancer. This is due to the favorable pharmacologic characteristics of fenretinide in colorectal cancer and the improved drug activity provided by nanoencapsulation.