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Background: Tirbanibulin 1% ointment is approved for the field treatment of Olsen grade I actinic keratoses (AKs) of the face and scalp. Methods: We performed a multicenter retrospective study involving 15 dermatologic units in Italy to investigate the efficacy and tolerability of tirbanibulin in a real‐life setting. 250 patients were enrolled. Tirbanibulin, 1% ointment, was applied daily for five consecutive days. The efficacy of treatment was measured with modifications of the Actinic Keratosis Area and Severity Index (AKASI). A satisfactory response was defined by complete (100% reduction in the number of lesions) or partial clearance (75–99%) of treated AKs. Results: Overall, the AKASI score was significantly reduced in the studied population (mean, from 4.1 ± 2.7 to 1.4 ± 1.5; P < 0.001). A satisfactory response was observed in 222 (88.8%) cases. The proportion of satisfactory responses was higher when follow‐up was performed after 8 weeks (34/35, 97.1%). The reduction in AKASI was significant in patients with Olsen grade II or III lesions (from 5.3 ± 2.8 to 1.6 ± 1.6; P < 0.001). A satisfactory response was observed in 91/104 (87.5%) cases. AKASI reduction was also significant in patients with trunk or limb AKs (from 7.0 ± 1.3 to 2.0 ± 1.6; P = 0.018) since a satisfactory response was observed in 7/8 (87.5%) cases. Tirbanibulin was well tolerated; all adverse events (AEs) included transient local reactions at the site of treatment. Overall, 231 patients had at least one AE. Only 7 (2.8%) grade 4 AEs were recorded. Conclusion: Our retrospective study confirmed that tirbanibulin 1% ointment is effective and well tolerated in a real‐life setting and is also promising for Olsen grade II and grade III AKs and AKs localized on difficult‐to‐treat areas. [ABSTRACT FROM AUTHOR]

This paper examines the influence of climate change vulnerability on the likelihood and severity of communal violence, with a particular emphasis on delineating large-scale regional patterns. Specifically, the analysis centres on Sub-Saharan Africa and South/South-East Asia – both regions being predominantly characterised by rain-fed agriculture and climate-sensitive economic activities – spanning the years 1995 to 2021. Relying on the ND-GAIN Vulnerability Index as a multidimensional measure for propensity of societies to be negatively impacted by climate change, we found robust evidence that greater vulnerability is conducive to a higher likelihood and severity of communal violence in Sub-Saharan Africa. On the other hand, in South/South-East Asia, results suggest that current climate variability, measured as rainfall deviations within the period, exerts a greater effect on communal violence outbreak than overall vulnerability to climate change. In both regions, greater access to productive means is significantly associated to the reduction of communal violence. [ABSTRACT FROM AUTHOR]

It is well known that during prolonged, high-intensity physical training, athletes experience a state of immunosuppression and that balanced nutrition can help maintain immunity. This review summarizes the effects (amplified by virus infection) of high-intensity, long-term exercise on immunity, critically presenting key micronutrients and supplementation strategies that can influence athletes' performance and their immune system. The main conclusion is that micronutrient supplementation with diet could help to protect the immune system from the stress effects induced by intense physical activities. The importance of personalized supplementation has been also recommended. [ABSTRACT FROM AUTHOR]

Introduction: Oncogenic tyrosine kinases (TK) are enzymes that play a key role in cell growth and proliferation and their mutations can lead to uncontrolled cell growth and development of aggressive cancer. This knowledge has led to the development of new classes of drugs, Tyrosine kinase inhibitors (TKI). They target oncogenic kinases who are associated with advanced radioactive iodine (RAI) refractory TC, which is not able to uptake RAI anymore and/or still grows between consecutive treatments with Iodine 131 (I131). Areas covered: Since Lenvatinib and Sorafenib approval, several other molecular inhibitors have been studied and then introduced for the treatment of aggressive and refractory thyroid cancer (TC), and, although the development of adverse effects or tumor resistance mechanisms, more and more compounds are still under investigation. The literature search was executed in PubMed and ClinicalTrials.gov to identify relevant articles and clinical trials published until December 2023. Expert opinion: In the context of clinical trials, driven by the presence of specific molecular mutations or even in the absence of both conditions, systemic therapy TKIs are valuable weapons to be used in patients affected by aggressive forms of TC, waiting for further expansion of the treatment landscape with more efficacious and safer drugs. [ABSTRACT FROM AUTHOR]

We report an unprecedented iron‐catalyzed C−H annulation using readily available 2‐vinylbenzofurans as the reaction pattern. The redox‐neutral strategy, based on cheap, non‐toxic, and earth‐abundant iron catalysts, exploits triazole assistance to promote a cascade C−H alkylation, benzofuran ring‐opening and insertion into a Fe−N bond, to form highly functionalized isoquinolones. Detailed mechanistic studies supported by DFT calculations fully disclosed the manifold of the iron catalysis. [ABSTRACT FROM AUTHOR]

We report an unprecedented iron‐catalyzed C−H annulation using readily available 2‐vinylbenzofurans as the reaction pattern. The redox‐neutral strategy, based on cheap, non‐toxic, and earth‐abundant iron catalysts, exploits triazole assistance to promote a cascade C−H alkylation, benzofuran ring‐opening and insertion into a Fe−N bond, to form highly functionalized isoquinolones. Detailed mechanistic studies supported by DFT calculations fully disclosed the manifold of the iron catalysis. [ABSTRACT FROM AUTHOR]

Introduction: This is an observational and retrospective study, in which we have analyzed data from patients affected by gastric diseases (p) who have been treated with liquid L-T4 (L-LT4;84 p), or tablet L-T4 (T-LT4;120 p), for the replacement therapy of hypothyroidism. The aim of the study is to compare the stability of TSH [normal range, 0.3-3.5 mIU/ml] in these patients. Methods: All p assumed L-T4 30 minutes before breakfast. The types of gastric disease were: a) T-LT4 group: 74 chronic gastritis (CG); 4 gastrectomy for gastric cancer (GTx); 42 gastro-plastics (GP); b) L-LT4 group: 60 CG; 3 GTx; 21 GP (p>0.05). 66% p in T-LT4 group were chronically treated with proton pump inhibitors (PPI), against 51% in L-LT4 group (p>0.05). The frequency of Helicobacter Pylori infection was 17% in both T-LT4 and L-LT4 groups. The gender distribution, mean age and body weight were similar in the 2 groups (p>0.05). The mean L-T4 dosage in T-LT4 group at the basal evaluation was 1.22 +/-0.27 mg/kg/die, in the L-LT4 group 1.36+/-0.22 µg/kg/die (p>0.05). Results: At the basal evaluation the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 36%, in L-LT4 group 46% (p<0.05). After adjustment of the dosage of the LT-4 therapy, the p were re-evaluated in an interval range of 5-9 months, for 4 times, during an overall period ranging from 23 to 31 months. At the first re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL was 13% in both groups. At the second re-evaluation, the prevalence of p with a TSH>3.5 µIU/mL in T-LT4 group was 26%, in L-LT4 group 13% (p>0.05). At the third re-evaluation, the prevalence of p with TSH<3.5 mIU/mL in T-LT4 group was 19%, in L-LT4 group 9% (p=0.05). At the fourth and last re-evaluation, the prevalence of patients with a TSH>3.5 µIU/mL in T-LT4 group was 18%, in L-LT4 group 5% (p<0.05). Mean FT4 and FT3 circulating levels were not significantly different in the two group at each visit. Discussion: These data suggest that the liquid L-T4 formulation therapy can result in a more stable control of TSH levels in hypothyroid patients with gastric disorders in the long-term follow-up. [ABSTRACT FROM AUTHOR]

Cardiovascular disease (CVD) remains the leading cause of death worldwide, representing a major health issue of social and economic relevance. Both hyperthyroidism and hypothyroidism are very common in the adult population, and both disorders may contribute to the onset and progression of CVD. After a brief description of the role of thyroid hormones (THs) on the physiology of the cardiovascular system and the potential mechanism that links THs alterations with changes in cardiac function, blood pressure, endothelial function, and lipid levels, we review updated data about the clinical impact of overt hypothyroidism (OH) and subclinical hypothyroidism(SCH) on CV risk, CVD, andmortality. Furthermore, we summarize the current evidence for treating SCH with levothyroxine (L-T4). Several guidelines of distinguished endocrine societies recommend treatment for SCH with TSH higher than 10 mIU/L, where the benefit of L-T4 therapy is more evident for younger people, but still controversial in those aged over 65 years. Based on current knowledge, more research efforts are needed to better address the clinical management of CV risk and CVD in the elderly affected by SCH. [ABSTRACT FROM AUTHOR]

Anaplastic thyroid cancer (ATC) is one of the deadliest human cancers and represents <2% of thyroid carcinomas. A therapeutic target for ATC is represented by anaplastic lymphoma kinase (ALK) rearrangements, involved in tumor growth. Crizotinib is an oral small-molecule tyrosine kinase inhibitor of the ALK, MET, and ROS1 kinases, approved in ALK-positive non-small cell lung cancer. Until now, the effect of crizotinib in "primary human ATC cells" (pATCs) with transforming striatin (STRN)–ALK fusion has not been reported in the literature. In this study, we aimed to obtain pATCs with STRN–ALK in vitro and evaluate the in vitro antineoplastic action of crizotinib. Thyroid surgical samples were obtained from 12 ATC patients and 6 controls (who had undergone parathyroidectomy). A total of 10/12 pATC cultures were obtained, 2 of which with transforming STRN–ALK fusion (17%). Crizotinib inhibited proliferation, migration, and invasion and increased apoptosis in 3/10 pATC cultures (2 of which with/1 without STRN–ALK), particularly in those with STRN–ALK. Moreover, crizotinib significantly inhibited the proliferation of AF cells (a continuous cell line obtained from primary ATC cells). In conclusion, the antineoplastic activity of crizotinib has been shown in human pATCs (with STRN–ALK) in preclinical studies in vitro, opening the way to future clinical evaluation in these patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Sinonasal cancer (SNC) is strongly associated with occupational exposure to several carcinogens involved in SNC's etiology, which vary by gender. Gender differences in SNC cases were examined through the Italian sinonasal cancer registry. Male-to-female incidence differences are neglectable in the youngest age classes but increase in older age classes, probably as a result of more men being diagnosed with SNC due to their greater occupational exposure to carcinogens (mostly wood and leather dusts) compared with women. Occupational exposures to carcinogens were the most frequent in both genders. A high percentage of women had unlikely exposures. Gender differences deserve more deep investigation, starting with a review of diagnostic processes and occupational history taking. Background: Although rare, sinonasal cancers (SNCs) have a high occupational attributable fraction. Methods: We applied gender-based approaches to descriptive analyses, incidence, and patterns of exposures using the Italian National Sinonasal Cancer Registry (ReNaTuNS: Registro Nazionale Tumori Naso-Sinusali). Results: The study included 2851 SNC patients. SNC was diagnosed more often in men (73%) than in women (27%). The most frequent morphology in men was intestinal-type adenocarcinoma (33%), whereas in women, it was squamous cell carcinoma (49%). Nasal cavities were predominant in both genders (50%), ethmoidal sinus in men (24%), and maxillary in women (24%). Incidence rates were 0.76 (per 100,000 person-years) in men and 0.24 in women and increased by age, more evidently in men, peaking over 75 years in both. Occupational exposures to wood and leather dusts were the most frequent (41% for men, 33% for women). Few exposures were extra-occupational or domestic. Unlikely exposure was relevant in women (57%). Conclusions: The surveillance of SNC cases through a registry that allows for the identification of and compensation for this occupational disease is important in Italy, where numerous workers are exposed to carcinogens for SNC, without even being aware. Considering the rarity of the disease, particularly among women, the ReNaTuNS can provide a method to analyze gender differences. [ABSTRACT FROM AUTHOR]

In hypothyroid patients needing large doses of levothyroxine (L-T4) (>1.7-2 mg/kg/day) to reach euthyroidism, lactose intolerance (LI) needs to be excluded, owing to the high prevalence in the population. If LI is present, a lactose-free diet decreases the rate of L-T4 malabsorption. However, an increased requirement of L-T4 is described in patients with LI, which can be beneficially treated using lactose-free L-T4 formulation. The lactose-free liquid L-T4 formulation is able to circumvent LI malabsorption leading to the normalization of thyroid-stimulating hormone (TSH) in patients with subclinical hypothyroidism and long-term stable TSH levels. [ABSTRACT FROM AUTHOR]

This article explores the use of biologics in psoriatic patients who have had a malignancy. While there are concerns about the safety of biologics in psoriasis, their use in oncologic patients is still uncertain. Guidelines recommend avoiding biologics in individuals with a current or recent malignancy, unless it has been treated more than 5 years ago. However, biologics may be considered in patients with severe psoriasis and a recent malignancy diagnosis. The article presents the findings of a study conducted in Italy, which evaluated the impact of a cancer diagnosis in psoriatic patients treated with biologics. The study analyzed three groups of patients and found that restarting biologic therapy after a cancer diagnosis did not significantly increase the risk of cancer recurrence. The study suggests that biologics can be considered as a treatment option for patients with a history of malignancy, but more research is needed. [Extracted from the article]

Simple Summary: There are clear links between wildlife trade and emerging infectious diseases including zoonotic diseases. In some cases, this leads to global outbreaks or even pandemics as recently seen with SARS and COVID-19 for instance. One of the first properly documented global pandemics caused by the trade of wildlife at a global level was the Great Parrot Fever Pandemic of 1929/1930. This pandemic was caused by psittacosis, a respiratory disease that can be transmitted to humans from infected birds (once transmitted to humans the disease is known as avian chlamydiosis). We assessed the risk of psittacosis becoming a zoonotic disease in Indonesia's bird markets where a wide range of wild-caught species, including parrots, are traded. In 14 markets on the islands of Java and Bali, we recorded almost 4500 parrots of 21 genera from all parts of the world and these were traded alongside each other. Genera offered for sale together did not cluster into geographic groups, were sold during all months of the year, and for 12/21 genera the presence of psittacosis had been reported in the past. We conclude that the omnipresence of wild-caught parrots from various geographic regions in large numbers within the same bird markets (visited by 100 s of people daily) increases the likelihood that psittacosis is indeed present. This poses a real risk for the zoonotic spread of avian chlamydiosis to humans. Wildlife trade, both legal and illegal, is increasingly recognized as a key factor in the rise of emerging viral infectious diseases, and this is especially apparent in Asia, where large numbers of wildlife are openly offered for sale in bird markets. We here focus on the risk of Psittacosis becoming a zoonotic disease in the wildlife markets of Java and Bali, Indonesia. Psittacosis is particularly prevalent in parrots (hence the name), and the trade in parrots was instrumental in the Great Parrot Fever Pandemic in 1929/1930. Between 2014 and 2023, we conducted 176 surveys of 14 bird markets, during which we recorded 4446 largely wild-caught parrots for sale. On average, each market had nine genera on offer, and the diversity of genera increased with the increasing presence of parrots (up to 16 genera). For most of the bird markets during each survey, parrots from different genera and originating from different parts of the world, were offered for sale alongside each other. Genera offered for sale together did not cluster into natural (geographic) groups. We found no temporal difference in the sale of parrots. We conclude that the omnipresence of wild-caught parrots from various geographic regions in large numbers within the same bird markets increases the risk that psittacosis is present and that this poses a real risk for the zoonotic spread of avian chlamydiosis to humans. [ABSTRACT FROM AUTHOR]

A recent Italian study examined the immune response to the COVID-19 vaccine among psoriatic patients receiving biological therapy. The study included 346 psoriatic patients and 151 controls who received two doses of the vaccine and were tested for antibodies. The results showed that both groups had a strong antibody response, with no significant difference between patients and controls. Mild adverse events were reported by about one-fourth of participants, and no serious adverse events were reported. The study also found that the type of vaccine administered was associated with antibody levels, with higher levels observed in those vaccinated with Janssen and lower levels in those vaccinated with AstraZeneca. However, the number of subjects who received these vaccines was limited. The study suggests that COVID-19 vaccinations are effective and safe for psoriatic patients undergoing biological treatments. [Extracted from the article]

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders caused by the interaction of genetic, environmental, and familial factors. These diseases have distinct pathologies and symptoms that are linked to specific cell populations in the brain. Notably, the immune system has been implicated in both diseases, with a particular focus on the dysfunction of microglia, the brain's resident immune cells, contributing to neuronal loss and exacerbating symptoms. Researchers use models of the neuroimmune system to gain a deeper understanding of the physiological and biological aspects of these neurodegenerative diseases and how they progress. Several in vitro and in vivo models, including 2D cultures and animal models, have been utilized. Recently, advancements have been made in optimizing these existing models and developing 3D models and organ-on-a-chip systems, holding tremendous promise in accurately mimicking the intricate intracellular environment. As a result, these models represent a crucial breakthrough in the transformation of current treatments for PD and AD by offering potential for conducting long-term disease-based modeling for therapeutic testing, reducing reliance on animal models, and significantly improving cell viability compared to conventional 2D models. The application of 3D and organ-on-a-chip models in neurodegenerative disease research marks a prosperous step forward, providing a more realistic representation of the complex interactions within the neuroimmune system. Ultimately, these refined models of the neuroimmune system aim to aid in the quest to combat and mitigate the impact of debilitating neuroimmune diseases on patients and their families. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common type of differentiated TC, while medullary TC (MTC) accounts for 4%. The concomitant presence of PTC and MTC is rare. Methods: This is a retrospective, single-center observational study conducted over 16 years (2001–2017). The data were collected from the clinical records of patients who underwent total thyroidectomy at the Endocrine Unit-Department of Medicine of the University Hospital of Pisa, Italy. Results: Over 690 analyzed cases, 650 (94.2%) were exclusive DTC, 19 exclusive MTC (2.75%) and 5 PTC/MTC (0.7%). No case of mixed medullary/follicular TC or hereditary MTC (familial MTC/multiple endocrine neoplasia type 2) was found. Among the five PTC/MTC cases, there was a male prevalence (M:F = 3:2), and all PTC components were at stage I, whereas 40% of MTC were at stage I and III and 20% of MTC were at stage II; microPTC (mPTC) was prevalent (80%) and also microMTCs were frequent (40%); 60% of MTC patients recovered, while 40% of patients developed metastatic disease. The search for germline mutations of the RET gene resulted in being negative in all cases. Conclusions: The incidence of PTC/MTC has been increasing over the past 30 years. The etiology of PTC/MTC forms is still unknown, and although this simultaneous occurrence could be only a coincidence, we cannot exclude the hypothesis of a shared genetic origin. [ABSTRACT FROM AUTHOR]

Background: Janus kinase (JAK) inhibitors, including upadacitinib, have been recently approved for the treatment of moderate-severe atopic dermatitis (AD) and real-world data on upadacitinib effectiveness and safety are limited. This interim analysis aimed to assess effectiveness and safety of upadacitinib throughout 48 weeks of observation in a real-world adult AD population. Methods: This prospective study collected data on adult patients affected by moderate-to-severe AD and treated with upadacitinib at the dosage of either 15 mg or 30 mg daily based on the physician decision. Upadacitinib was prescribed in the context of a national compassionate use programme. In this interim analysis, within patient comparisons of continuous scores of different scales (namely Eczema Area and Severity Index [EASI], body surface area [BSA], Dermatology Life Quality Index [DLQI], Patient Oriented Eczema Measure [POEM], Numeric Rating Scale [NRS] subtests) were performed. The percentage of patients achieving EASI 75, EASI 90 and EASI 100 at Week 16, 32 and 48 was also evaluated. Results: One hundred and forty-six patients were included in the analysis. Upadacitinib 15 mg or 30 mg daily was prescribed as monotherapy in most cases (127/146, 87.0%). Upadacitinib was initially prescribed at the dosage of 30 mg daily in 118 of 146 (80.8%) patients and 15 mg daily in 28/146 (19.2%) patients. A significant improvement in the clinical signs and symptoms of AD was detected by Week 16 and throughout the study period. EASI 75, EASI 90 and EASI 100 responses were achieved by 87.6%, 69.1% and 44.3% at Week 48, associated with a sustained reduction in the mean values of all physician-reported (EASI and BSA) and patient-reported (Itch- Sleep- and Pain-NRS, DLQI, and POEM) disease severity outcomes, up to 48 weeks of treatment. Treatment response observed in 15 mg upadacitinib-treated patients was comparable with that detected in 30 mg upadacitinib-treated patients, revealing no statistical difference between the two patient sub-cohorts. Through the observation period, dose reduction or escalation was observed in 38/146 (26%) of treated cases. Overall, 26 of 146 (17.8%) patients experienced at least one adverse event (AE) during the treatment period. In total, 29 AEs were recorded and most of them were evaluated as mild to moderate, while in 4 cases the occurrence of AE led to drug discontinuation, for a total of 7/146 (4.8%) dropouts. Conclusion: This study provides strong evidence of a sustained response obtained by upadacitinib in AD patients, who had failed to respond to conventional or biological systemic agents, through 48 weeks of observation. Upadacitinib was also demonstrated to be advantageous in terms of flexibility in dose reduction or escalation as upadacitinib dose was shaped on clinical needs that, in a real-world setting, might frequently change. [ABSTRACT FROM AUTHOR]

Background: Sepsis is the third leading cause of neonatal death in low and middle-income countries, accounting for one third of all deaths in Ethiopia. A concerning issue is the increasing number of multidrug-resistant microorganisms facilitated by suboptimal antibiotic stewardship. The study aims to identify clusters of newborns switching antibiotic lines for sepsis in a neonatal intensive care unit (NICU) in Ethiopia, and to explore their potential association with sepsis outcomes. Methods: A retrospective cohort study was conducted including all newborns discharged with a diagnosis of probable neonatal sepsis from the St. Luke Catholic Hospital NICU between April and July 2021. The antibiotic management protocol included two lines according to WHO guidelines and a third line based on internal hospital guidelines. In the cluster analysis, the Gower distance was estimated based on the antibiotics employed in the different lines and the duration of each line. Mortality and respiratory distress (RD) were the response variables. Results: In the study period, 456 newborns were admitted to the NICU and 196 (42.8%) had probable neonatal sepsis. Four antibiotic management clusters were identified. Cluster 1 (n = 145, 74.4%) had no antibiotic switches, using only the first line. Cluster 2 (n = 26, 13.3%) had one switch from the first to the second line. Cluster 4 (n = 9, 4.6%) had two switches: from first to second and then to third line. In cluster 3 (n = 15, 7.7%), newborns were switched from ceftriaxone/cloxacillin as second line to off-protocol antibiotics. There were no differences in sex, age, weight on admission or crude mortality between clusters. Cluster 3 included a higher frequency of infants who did not breathe at birth (53.3%, p = 0.011) and that necessitated bag ventilation (46.7%, p = 0.039) compared to the other clusters. Conclusions: The first antibiotic line failed in one out of four newborns with probable sepsis while third-generation cephalosporins were insufficient in one in ten patients. Cluster analysis can provide valuable insights into antibiotic treatment patterns and their potential implications. This approach may support antibiotic stewardship and aid in contrasting antimicrobial resistance in limited resource settings. [ABSTRACT FROM AUTHOR]

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiological culprit of COronaVIrus Disease 19 (COVID-19), can enter the cells via the angiotensin-converting enzyme 2 (ACE2) receptor, which has been found in several tissues including in endocrine organs, such as the ovaries, testes, pancreas, and thyroid. Several thyroid disorders have been associated with SARS-CoV-2 infection [subacute thyroiditis (SAT), thyrotoxicosis, and non-thyroidal illness syndrome (NTIS)] and, in part, they are believed to be secondary to the local virus replication within the gland cells. However, as documented for other viruses, SARS-CoV-2 seems to interfere with several aspects of the immune system, inducing the synthesis of autoantibodies and triggering latent or new onset autoimmune disease (AID), including autoimmune thyroid disease (AITD), such as Hashimoto Thyroiditis (HT) and Graves' disease (GD). Several mechanisms have been hypothesized to explain this induction of autoimmunity by SARS-CoV-2 infection: the immune system hyper-stimulation, the molecular mimicry between the self-antigens of the host and the virus, neutrophils extracellular traps, and finally, the virus induced transcriptional changes in the immune genes; nonetheless, more evidence is needed especially from large, long-term cohort studies involving COVID-19 patients, to establish or reject this pathogenetic relationship. [ABSTRACT FROM AUTHOR]

Simple Summary: Up to 80% of disease relapse within 2 years after resection of colorectal cancer liver metastases occurs in patients with high burden of disease. Increase in life expectancy with new chemotherapy protocols opens the new challenge of maintaining quality of life after disease relapse and of offering subsequent surgical options when feasible. First-order glissonean-pedicles division recurrence should be absolutely avoided since it may hamper the subsequent administration of systemic treatments and worsen patient's quality of life due to biliary involvement. To this end, selected cases of metastases at the hepatocaval-confluence were treated with vessel-guided mesohepatectomy of segments 1 and 4 en-bloc with the middle hepatic vein. This minor liver resection induces a major hepatic scaffold modification, transforming the liver into a paired organ. This novelty led us to use for the first time liver augmentation techniques in a parenchyma-sparing context, observing a liver regeneration never described before. Based on our results, this surgical approach may represent a new option for patients affected by colorectal liver metastases selected in the frame of an experienced multidisciplinary environment including dedicated oncologists, anesthesiologists, radiologists, pathologists and surgeons. Background. R0 minor parenchyma-sparing hepatectomy (PSH) is feasible for colorectal liver metastases (CRLM) in contact with hepatic veins (HV) at hepatocaval confluence since HV can be reconstructed, but in the case of contact with the first-order glissonean pedicle (GP), major hepatectomy is mandatory. To pursue an R0 parenchyma-sparing policy, we proposed vessel-guided mesohepatectomy for liver partition (MLP) and eventually combination with liver augmentation techniques for staged major PSH. Methods. We analyzed 15 consecutive vessel-guided MLPs for CRLM at the hepatocaval confluence. Patients had a median of 11 (range: 0–67) lesions with a median diameter of 3.5 cm (range: 0.0–8.0), bilateral in 73% of cases. Results. Grade IIIb or more complications occurred in 13%, median hospital stay was 14 (range: 6–62) days, 90-day mortality was 0%. After a median follow-up of 17.5 months, 1-year OS and RFS were 92% and 62%. In nine (64%) patients, MLP was combined with portal vein embolization (PVE) or ALPPS to perform staged R0 major PSH. Future liver remnant (FLR) volume increased from a median of 15% (range: 7–20%) up to 41% (range: 37–69%). Super-selective PVE was performed in three (33%) patients and enhanced ALPPS (e-ALPPS) in six (66%). In two e-ALPPS an intermediate stage of deportalized liver PSH was necessary to achieve adequate FLR volume. Conclusions. Vessel-guided MLP may transform the liver in a paired organ. In selected cases of multiple bilobar CRLM, to guarantee oncological radicality (R0), major PSH is feasible combining advanced surgical parenchyma sparing with liver augmentation techniques when FLR volume is insufficient. [ABSTRACT FROM AUTHOR]

Eleven of the 26 patients (42.3%) had chronic HBV infection, seven (26.9%) had a serology compatible with a previous or an occult HBV infection, and eight (30.8%) had resolved HBV infection. Serum HBV-DNA load was undetectable in all patients with previous/occult and resolved HBV infection, and in 7/11 patients with chronic HBV infection. We performed a multicentric retrospective cohort study on 26 consecutive psoriasis patients with HBV infection and 23 patients with HCV infection treated with risankizumab. [Extracted from the article]

In 1990, Gorlin et al. described four types of craniofacial duplications: (1) single mouth with duplication of the maxillary arch; (2) supernumerary mouth laterally placed with rudimentary segments; (3) single mouth with replication of the mandibular segments; and (4) true facial duplication, namely diprosopus. We describe a newborn born with wide-spaced eyes, a very broad nose, and two separate mouths. Workup revealed the absence of the corpus callosum and the presence of a brain midline lipoma, wide sutures, and a Chiari I malformation with cerebellar herniation. We conducted a systematic review of the literature and compared all the cases described as diprosopus. In 96% of these, the central nervous system is affected, with anencephaly being the most commonly associated abnormality. Other associated anomalies include cardiac malformations (86%), cleft palate (63%), diaphragmatic hernia (13%), and disorder of sex development (DSD) (13%). Although the facial features are those that first strike the eye, the almost obligate presence of cerebral malformations suggests a disruptive event in the cephalic pole of the forming embryo. No major monogenic contribution has been recognized today for this type of malformation. [ABSTRACT FROM AUTHOR]

Aim: Even if a defunctioning stoma mitigates the serious consequences of anastomotic leakage after total mesorectal excision (TME) for rectal cancer, the presence of a temporary stoma or having a stoma for a prolonged period of time may also be a determining factor for further morbidities and poor bowel function. The aim of this study was to evaluate the impact of diverting stomas on clinical and functional outcomes after TME, comparing ileostomy or colostomy effects. Methods: All consecutive patients who underwent TME for rectal cancer between March 2017 and December 2020 in three Italian referral centres were enrolled in the present study. For every patient sex, age, stage of the tumour, neoadjuvant therapy, surgical technique, anastomotic technique, the presence of a diverting stoma, perioperative complications and functional postoperative status were recorded. Considering the diverting stoma, the kind of stoma, length of time before closure and stoma related complications were evaluated. Results: During the study period 416 consecutive patients (63% men) were included. Preoperative neoadjuvant therapy was performed in 79%. A minimally invasive approach was performed in >95% of patients. Temporary stoma was performed during the operation in 387 patients (93%) (ileostomy 71%, colostomy 21%). The stoma was closed in 84% of patients. The median time from surgery to stoma closure was 145 days. No difference was found between ileostomy and colostomy in overall morbidity after stoma creation and closure. Moreover, increased postoperative functional disturbance seemed to be significantly proportional to the attending time for closure for ileostomy. Conclusion: The presence of a defunctioning stoma seems to have a negative impact on functional bowel activity, especially for delayed closure for ileostomy. This should be considered when the kind of stoma (ileostomy vs. colostomy) is selected for each patient. [ABSTRACT FROM AUTHOR]

Nurses and paramedics play a pivotal role when mass casualty incidents (MCI) occur, yet they often feel unprepared for such events. Implementation strategies for training activities, including virtual reality (VR) and augmented reality (AR) simulations, offer realistic and immersive learning experiences, enhancing skills and competencies for nursing students. The aim of this work was to investigate the adopted tools in studies on VR and AR simulations for training nursing and paramedic students in managing MCI. A scoping review was performed following the PRISMA-ScR statement, and the search strategy was conducted through five electronic databases from December 2022 to March 2023. Of 162 records identified, 27 full texts were screened and, six studies were included in this review. These studies involved students who were assigned to different training methods, including immersive VR simulation, written instruction, and traditional lecture. VR and AR and immersive simulation generally show promising evidence in enhancing practical skills and knowledge in MCI management. VR and AR showed to be promising in disaster education and preparedness training, offering different levels of immersiveness and engagement, encouraging active and experiential learning. Further research is needed to determine their long-term effectiveness. The choice of training method should consider program goals, target population, and available resources. [ABSTRACT FROM AUTHOR]

Azocalixarenes functionalized with cation binding sites are popular chromoionophores due to the ease of synthesis and the large complexation-induced shifts of their absorption band that originate from an azo-phenol–quinone-hydrazone tautomerism. Despite their extensive use, however, a thorough investigation of the structure of their metal complexes has not been reported. We describe herein the synthesis of a new azocalixarene ligand (2) and the study of its complexation properties with the Ca2+ cation. Through a combination of solution (1H NMR and UV-vis spectroscopies) and solid-state (X-ray diffractometry) techniques, we demonstrate that metal complexation induces a shift of the tautomeric equilibration towards the quinone-hydrazone form, while deprotonation of the complex results in the reversion to the azo-phenol tautomer. [ABSTRACT FROM AUTHOR]

We report the synthesis and characterisation of [2]rotaxanes based on a stilbazolium dye and a calix[6]arene macrocycle. Since both components are non-symmetric, two orientational isomers are obtained. The two isomers display distinct photophysical and photochemical properties in solution and solid state, superior to the unencapsulated dye. [ABSTRACT FROM AUTHOR]

Breast cancer (BC), the most commonly diagnosed malignancy, frequently metastasizes to the bone, lungs, brain and liver at advanced stages, whereas the thyroid gland represents a rare target site for secondary disease. We examined the most recent literature about thyroid metastasis (TM) from BC after we encountered a peculiar case of a 71-year-old woman who developed sudden dysphagia, severe hypothyroidism and hypoparathyroidism due to TM 18 years after the diagnosis of her primary cancer. Based on published data, the prevalence of TM in BC ranges from 3% to 34%, with a median onset time of 48.2 months, although longer time intervals are not infrequent. TM negatively impacts the prognosis of these patients, however thyroid surgery can limit the local disease burden. Therefore, we suggest that clinicians involved in the follow-up care of BC patients should consider a differential diagnosis of secondary thyroid malignancy when incidental lesions are diagnosed during radiological evaluations or local symptoms affect the cervical region, even many years after the diagnosis of the primary cancer. [ABSTRACT FROM AUTHOR]

A common feature of different types of diabetes is the high blood glucose levels, which are known to induce a series of metabolic alterations, leading to damaging events in different tissues. Among these alterations, both increased polyol pathway flux and oxidative stress are considered to play relevant roles in the response of different cells. In this work, the effect on a human lens epithelial cell line of stress conditions, consisting of exposure to either high glucose levels or to the lipid peroxidation product 4-hydroxy-2-nonenal, is reported. The occurrence of osmotic imbalance, alterations of glutathione levels, and expression of inflammatory markers was monitored. A common feature of the two stress conditions was the expression of COX-2, which, only in the case of hyperglycemic stress, occurred through NF-κB activation. In our cell model, aldose reductase activity, which is confirmed as the only activity responsible for the osmotic imbalance occurring in hyperglycemic conditions, seemed to have no role in controlling the onset of the inflammatory phenomena. However, it played a relevant role in cellular detoxification against lipid peroxidation products. These results, in confirming the multifactorial nature of the inflammatory phenomena, highlight the dual role of aldose reductase as having both damaging but also protecting activity, depending on stress conditions. [ABSTRACT FROM AUTHOR]

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous syndrome causing hamartomatous growths in multiple organs. Facial angiofibromas occur in up to 80% of patients and can be highly disfiguring. Treatment for these lesions is challenging. Recently, topical rapamycin has been proposed as an effective option to treat angiofibromas but a commercially available compound has not yet been developed in Europe. We conducted a retrospective review with the aim to update the current data on the use of topical rapamycin in the treatment of angiofibromas in TSC, focusing on the optimal concentration and trying to establish which vehicle should be preferred. Thirty‐nine reports describing the use of topical rapamycin in the treatment of angiofibromas in TSC were considered, involving a total of 483 patients. An improvement of the lesions has been shown in over 90% of subjects, particularly if the treatment was started at early stages. Several different formulations (ointment, gel, solution and cream) with a wide range of concentrations (0.003%–1%) were proposed, of which a pharmacological analysis has also been performed. Topical rapamycin can be considered an effective and safe option for the treatment and the prevention of facial angiofibromas in younger patients, but the best formulation has yet to be established. Our review demonstrates that ointment and gel should be preferred, but it is not clear which concentration is optimal. However, according to this study, the 0.1% concentration represents the first choice. Long‐term and comparative studies between topical rapamycin formulations are required in order to establish which treatment has a better outcome and lower recurrence rate. [ABSTRACT FROM AUTHOR]

Co-infection with other STDs was observed in 35% of patients, with gonorrhoea being the most commonly reported. All patients had skin manifestations, with 33% reporting skin lesions before developing systemic signs/symptoms (mean: 7 days before, IQR: 1-10). All patients recovered within 21 days, except for one patient who experienced recurrent lesions and required a second isolation period. [Extracted from the article]

In summary, this international registry showed a rather stable disease activity in the majority of AIBD patients following COVID-19 infection. Death occurred in nine patients (13%) with a mean age of 84.3 years; 6 of the 9 patients (67%) of them died during hospitalization for COVID-19 infection. Respectively, the change in disease activity of AIBD before and after COVID-19 infection is shown in Figure 1d. 1 TABLE Reported systemic treatment for AIBD before and after COVID-19 infection. [Extracted from the article]

This article discusses the use of upadacitinib, a Janus kinase (JAK) inhibitor, in the treatment of multiple chronic inflammatory skin diseases. The case study focuses on a 21-year-old female patient with alopecia areata, psoriasis, and vitiligo. The patient was treated with upadacitinib and showed significant improvement in all three conditions. The article highlights the potential of upadacitinib as a single drug treatment for multiple dermatological diseases, but emphasizes the need for further research to establish treatment guidelines and assess long-term safety. [Extracted from the article]

Little is known on the effects of respiratory patterns on baroreflex function in heart failure (HF). Patients with HF (n = 30, age 61.6 ± 10 years, mean ± SD) and healthy controls (CNT, n = 10, age 58.9 ± 5.6 years) having their R–R interval (RRI, EKG), systolic arterial blood pressure (SBP, Finapres) and respiratory signal (RSP, Respitrace) monitored, were subjected to three recording sessions: free-breathing, fast- (≥ 12 bpm) and slow- (6 bpm) paced breathing. Baroreflex sensitivity (BRS) and power spectra of RRI, SBP, and RSP signals were calculated. During free-breathing, compared to CNT, HF patients showed a significantly greater modulation of respiratory volumes in the very-low-frequency (< 0.04 Hz) range and their BRS was not significantly different from that of CNT. During fast-paced breathing, when very-low-frequency modulations of respiration were reduced, BRS of HF patients was significantly lower than that of CNT and lower than during free breathing. During slow-paced breathing, BRS became again significantly higher than during fast breathing. In conclusion: (1) in free-breathing HF patients is present a greater modulation of respiratory volumes in the very-low-frequency range; (2) in HF patients modulation of respiration in the very-low and low frequency (around 0.1 Hz) ranges contributes to preserve baroreflex-mediated control of heart rate. [ABSTRACT FROM AUTHOR]

Little is known on the effects of respiratory patterns on baroreflex function in heart failure (HF). Patients with HF (n = 30, age 61.6 ± 10 years, mean ± SD) and healthy controls (CNT, n = 10, age 58.9 ± 5.6 years) having their R–R interval (RRI, EKG), systolic arterial blood pressure (SBP, Finapres) and respiratory signal (RSP, Respitrace) monitored, were subjected to three recording sessions: free-breathing, fast- (≥ 12 bpm) and slow- (6 bpm) paced breathing. Baroreflex sensitivity (BRS) and power spectra of RRI, SBP, and RSP signals were calculated. During free-breathing, compared to CNT, HF patients showed a significantly greater modulation of respiratory volumes in the very-low-frequency (< 0.04 Hz) range and their BRS was not significantly different from that of CNT. During fast-paced breathing, when very-low-frequency modulations of respiration were reduced, BRS of HF patients was significantly lower than that of CNT and lower than during free breathing. During slow-paced breathing, BRS became again significantly higher than during fast breathing. In conclusion: (1) in free-breathing HF patients is present a greater modulation of respiratory volumes in the very-low-frequency range; (2) in HF patients modulation of respiration in the very-low and low frequency (around 0.1 Hz) ranges contributes to preserve baroreflex-mediated control of heart rate. [ABSTRACT FROM AUTHOR]

Grade 37 titanium is widely used in racing applications thanks to its oxidation resistance up to 650 °C, but it suffers from poor wear and fretting resistance, especially at high temperature. In this paper, different surface modification techniques, namely, carburizing, coating by PVD-ZrO2 and a novel microwave plasma oxy-carburizing treatment, are investigated in terms of hardness, wear resistance and scratch hardness, compared to the untreated substrate. Numerical simulation allowed optimization of the design of the microwave plasma source, which operated at 2.45 GHz at atmospheric pressure. The proposed microwave plasma oxy-carburizing treatment is localized and can serve to improve the tribological properties of selected regions of the sample; compared to untreated Grade 37 titanium, the oxy-carburized layer presents a decrease in the wear rate at 450 °C against alumina of 54% and an increase in scratch hardness of more than three times. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a complex disease characterized by impaired glucose homeostasis and serious long-term complications. First-line therapeutic options for T2DM treatment are monodrug therapies, often replaced by multidrug therapies to ensure that non-responding patients maintain target glycemia levels. The use of multitarget drugs instead of mono- or multidrug therapies has been emerging as a main strategy to treat multifactorial diseases, including T2DM. Therefore, modern drug discovery in its early stages aims to identify potential modulators for multiple targets; for this purpose, exploration of the chemical space of natural products represents a powerful tool. Our study demonstrates that avarone, a sesquiterpene quinone obtained from the sponge Dysidea avara, is capable of inhibiting in vitro PTP1B, the main negative regulator of the insulin receptor, while it improves insulin sensitivity, and mitochondria activity in C2C12 cells. We observe that when avarone is administered alone, it acts as an insulin-mimetic agent. In addition, we show that avarone acts as a tight binding inhibitor of aldose reductase (AKR1B1), the enzyme involved in the development of diabetic complications. Overall, avarone could be proposed as a novel natural hit to be developed as a multitarget drug for diabetes and its pathological complications. [ABSTRACT FROM AUTHOR]

The transition areas between different tissues, known as tissue interfaces, have limited ability to regenerate after damage, which can lead to incomplete healing. Previous studies focussed on single interfaces, most commonly bone-tendon and bone-cartilage interfaces. Herein, we develop a 3D in vitro model to study the regeneration of the bone-tendon-muscle interface. The 3D model was prepared from collagen and agarose, with different concentrations of hydroxyapatite to graduate the tissues from bones to muscles, resulting in a stiffness gradient. This graduated structure was fabricated using indirect 3D printing to provide biologically relevant surface topographies. MG-63, human dermal fibroblasts, and Sket.4U cells were found suitable cell models for bones, tendons, and muscles, respectively. The biphasic and triphasic hydrogels composing the 3D model were shown to be suitable for cell growth. Cells were co-cultured on the 3D model for over 21 days before assessing cell proliferation, metabolic activity, viability, cytotoxicity, tissue-specific markers, and matrix deposition to determine interface formations. The studies were conducted in a newly developed growth chamber that allowed cell communication while the cell culture media was compartmentalised. The 3D model promoted cell viability, tissue-specific marker expression, and new matrix deposition over 21 days, thereby showing promise for the development of new interfaces. [ABSTRACT FROM AUTHOR]

Edge effects result from interactions between adjacent habitats, which can modify abiotic and biotic conditions and produce various negative effects on biodiversity. Given the high degree of forest fragmentation in Madagascar, understanding lemur responses to edges is a conservation priority. We aim to determine the depth of edge influence in a continuous low-land rainforest of south-eastern Madagascar and identify the response of six lemur species. We surveyed lemur abundance along nine 1 km transects from May 2015 to July 2016 totaling 112.2 km of survey effort during the day and 88.5 km at night. We characterized the habitat structure via 33 plots centered along the line transects. We used Generalized Additive Models and Generalized Linear Models to test the effect of distance from the forest edge on vegetation parameters and animal encounter rates. Edge effect on the vegetation structure can be detected up to around 100 m in terms of tree diversity and density. We found a negative edge response for Madame Fleurette's sportive lemurs (Lepilemur fleuretae) and collared brown lemurs (Eulemur collaris), and a positive edge response for Anosy mouse lemurs (Microcebus tanosi), Southern bamboo lemurs (Hapalemur meridionalis) and Southern woolly lemurs (Avahi meridionalis). Since around half of the forested areas in Madagascar are within 100 m of forest edge, taking into account edge effect is vital when producing estimates of population sizes and informing conservation management. [ABSTRACT FROM AUTHOR]

Reports concerning the beneficial effects of D-ribose administration in cardiovascular and muscle stressful conditions has led to suggestions for the use of ribose as an energizing food supplement for healthy people. However, this practice still presents too many critical issues, suggesting that caution is needed. In fact, there are many possible negative effects of this sugar that we believe are underestimated, if not neglected, by the literature supporting the presentation of the product to the market. Here, the risks deriving from the use of free ribose as ATP source, forcing ribose-5-phosphate to enter into the pentose phosphate pathway, is emphasized. On the basis of the remarkable glycation capacity of ribose, the easily predictable cytotoxic effect of the molecule is also highlighted. [ABSTRACT FROM AUTHOR]

The rise of antimicrobial-resistant phenotypes and the spread of the global pandemic of COVID-19 are worsening the outcomes of hospitalized patients for invasive fungal infections. Among them, candidiases are seriously worrying, especially since the currently available drug armamentarium is extremely limited. We recently reported a new class of macrocyclic amidinoureas bearing a guanidino tail as promising antifungal agents. Herein, we present the design and synthesis of a focused library of seven derivatives of macrocyclic amidinoureas, bearing a second phenyl ring fused with the core. Biological activity evaluation shows an interesting antifungal profile for some compounds, resulting to be active on a large panel of Candida spp. and C. neoformans. PAMPA experiments for representative compounds of the series revealed a low passive diffusion, suggesting a membrane-based mechanism of action or the involvement of active transport systems. Also, compounds were found not toxic at high concentrations, as assessed through MTT assays. [ABSTRACT FROM AUTHOR]

Introduction: Bullous pemphigoid is the most common autoimmune bullous dermatosis. In recent years several studies have tried to identify the main factors of the disease related with an increased risk of death. The aim of this multicenter Italian study was to assess the risk score of death considering epidemiologic, clinical, immunological, and therapeutic factors in a cohort of patients affected by bullous pemphigoid and try to identify the cumulative survival up to 120 months. Methods: We retrospectively reviewed the medical records of patients with bullous pemphigoid who were diagnosed between 2005 and 2020 in the 12 Italian centers. Data collected included sex, age at the time of diagnosis, laboratory findings, severity of disease, time at death/censoring, treatment, and multimorbidity. Results: A total of 572 patients were included in the study. The crude mortality rate was 20.6%, with an incidence mortality rate of 5.9 × 100 person/year. The mortality rate at 1, 3, 5, and 10 years was 3.2%, 18.2%, 27.4% and 51.9%, respectively. Multivariate model results showed that the risk of death was significantly higher in patients older than 78 years, in presence of multimorbidity, anti‐BP180 autoantibodies >72 U/mL, or anti‐BP230 > 3 U/mL at diagnosis. The variables jointly included provided an accuracy (Harrel's Index) of 77% for predicting mortality. Conclusion: This study represents the first nationwide Italian study to have retrospectively investigated the mortality rates and prognostic factors in patients with bullous pemphigoid. A novel finding emerged in our study is that a risk prediction rule based on simple risk factors (age, multimorbidity, steroid‐sparing drugs, prednisone use, and disease severity) jointly considered with two biomarkers routinely measured in clinical practice (anti‐BP230 and anti‐BP180 autoantibodies) provided about 80% accuracy for predicting mortality in large series of patients with this disease. [ABSTRACT FROM AUTHOR]

In order to explain the negative slope of appKM/appkcat versus inhibitor concentration observed in the study of epigallocatechin gallate acting as an inhibitor of aldose reductase, a kinetic analysis was performed to rationalise the phenomenon. Classical and non-classical models of complete and incomplete enzyme inhibition were devised and analysed to obtain rate equations suitable for the interpretation of experimental data. The results obtained from the different approaches were discussed in terms of the meaning of the emerging kinetic constants. A decrease of appKM/appkcat versus the inhibitor concentration was revealed to be a valuable indication of the occurrence of an incomplete inhibition. This indication, which is univocal in the case of an uncompetitive inhibition, may be especially useful when the residual activity resulting from inhibition is rather low. [ABSTRACT FROM AUTHOR]

Introduction: There is limited evidence to guide clinicians on the treatment of psoriasis with biologics in patients with a history of malignancy who are often excluded from clinical trials investigating biologics. The aim of this work is to report a multicenter real-life experience of secukinumab treatment in patients with psoriasis and a personal history of cancer. Methods: This retrospective observational study included adult patients with moderate-to-severe plaque psoriasis treated with secukinumab for at least 24 weeks and a previous diagnosis of cancer at 15 Italian referral centers. The primary endpoint of the study was tumor recurrence or progression and new cancer diagnosis during treatment. Secondary outcome assessment of secukinumab effectiveness (reduction of Psoriasis Area and Severity Index [PASI] score, improvement of Dermatology Life Quality Index [DLQI], itch and pain). Results: Forty-two patients (27 male) were included. Malignancy was diagnosed in the previous 5 years in 21 (56.8%) and in the previous 10 years in 37 (88.1%). The mean interval between cancer diagnosis and the start of secukinumab treatment was 3.5 ± 3.3 years. No tumor recurrence nor progression occurred over a mean of 56 ± 31.7 weeks of treatment. Three patients developed a new malignancy not related to the previous cancer. At week 48, PASI 90 was reached by 64.7% of patients and PASI 100 by 38.2%. Mean DLQI, itch, and pain VAS scores significantly improved during treatment. Conclusions: Our multicenter real-life experience is the largest reported to date focusing on a specific biologic and adds evidence to the safety of secukinumab in psoriatic patients with a personal history of cancer. [ABSTRACT FROM AUTHOR]

(1) Background: Infections in pregnancy can lead to miscarriage, premature birth, infections in newborns, and developmental disabilities in babies. Infected infants, symptomatic at birth, can have long-term sequelae, and asymptomatic babies are also at increased risk of developing long-term sensorineural outcomes. Targeted therapy of the pregnant mother can reduce fetal and neonatal harm. (2) Aim of the study: To explore the association between symptoms and time of onset of long-term sequelae in infected children born from mothers who contracted an infection during pregnancy, by a long-term multidisciplinary follow-up. (3) Methods: For up to 2–4 years, we evaluated cognitive, motor, audiological, visual, and language outcomes in infants with symptomatic and asymptomatic congenital infections and in uninfected infants. (4) Results: 186 infants born from women who acquired Cytomegalovirus infection (n = 103), Toxoplasma infection (n = 50), and Syphilis (n = 33) during pregnancy were observed. Among them, 119 infants acquired the infection in utero. Infected infants, symptomatic at birth, obtained lower scores on the Cognitive and Motor Scale on Bayley-III compared to asymptomatic and uninfected infants (p = 0.026; p = 0.049). Many severe or moderate sequelae rose up within the first year of life. At 24 months, we observed sequelae in 24.6% (14/57) of infected children classified as asymptomatic at birth, compared to 68.6% (24/35) of symptomatic ones (χ2 = 15.56; p < 0.001); (5) Conclusions: Infected babies symptomatic at birth have a worse prognosis than asymptomatic ones. Long-term sequelae may occur in infected children asymptomatic at birth after the first year of life. Multidisciplinary follow-up until 4–6 years of age should be performed in all infected children, regardless of the presence of symptoms at birth. [ABSTRACT FROM AUTHOR]

Among mammals, the order Primates is exceptional in having a high taxonomic richness in which the taxa are arboreal, semiterrestrial, or terrestrial. Although habitual terrestriality is pervasive among the apes and African and Asian monkeys (catarrhines), it is largely absent among monkeys of the Americas (platyrrhines), as well as galagos, lemurs, and lorises (strepsirrhines), which are mostly arboreal. Numerous ecological drivers and species-specific factors are suggested to set the conditions for an evolutionary shift from arboreality to terrestriality, and current environmental conditions may provide analogous scenarios to those transitional periods. Therefore, we investigated predominantly arboreal, diurnal primate genera from the Americas and Madagascar that lack fully terrestrial taxa, to determine whether ecological drivers (habitat canopy cover, predation risk, maximum temperature, precipitation, primate species richness, human population density, and distance to roads) or species-specific traits (bodymass, group size, and degree of frugivory) associate with increased terrestriality. We collated 150,961 observation hours across 2,227 months from 47 species at 20 sites in Madagascar and 48 sites in the Americas. Multiple factors were associated with ground use in these otherwise arboreal species, including increased temperature, a decrease in canopy cover, a dietary shift away from frugivory, and larger group size. These factors mostly explain intraspecific differences in terrestriality. As humanity modifies habitats and causes climate change, our results suggest that species already inhabiting hot, sparsely canopied sites, and exhibiting more generalized diets, are more likely to shift toward greater ground use. [ABSTRACT FROM AUTHOR]