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Abstract The engineering of non ribosomal peptide synthetases (NRPS) for new substrate specificity is a potent strategy to incorporate non-canonical amino acids into peptide sequences, thereby creating peptide diversity and broadening applications. The non-ribosomal peptide pyoverdine is the primary siderophore produced by Pseudomonas aeruginosa and holds biomedical promise in diagnosis, bio-imaging and antibiotic vectorization. We engineered the adenylation domain of PvdD, the terminal NRPS in pyoverdine biosynthesis, to accept a functionalized amino acid. Guided by molecular modeling, we rationally designed mutants of P. aeruginosa with mutations at two positions in the active site. A single amino acid change results in the successful incorporation of an azido-l-homoalanine leading to the synthesis of a new pyoverdine analog, functionalized with an azide function. We further demonstrated that copper free click chemistry is efficient on the functionalized pyoverdine and that the conjugated siderophore retains the iron chelation properties and its capacity to be recognized and transported by P. aeruginosa. The production of clickable pyoverdine holds substantial biotechnological significance, paving the way for numerous downstream applications.

Abstract Background The progressive aging of the population and the increasing complexity of health issues contribute to a growing number of older individuals seeking emergency care. This study aims to assess the state of the art of care provided to older people in the Emergency Departments of Lombardy, the most populous region in Italy, counting over 2 million people aged 65 years and older. Methods An online cross-sectional survey was developed and disseminated among emergency medicine physicians and physicians affiliated to the Lombardy section of the Italian Society of Geriatrics and Gerontology (SIGG), during June and July 2023. The questionnaire covered hospital profiles, geriatric consultation practices, risk assessment tools, discharge processes and perspectives on geriatric emergency care. Results In this mixed method research, 219 structured interviews were collected. The majority of physicians were employed in hospitals, with 54.7% being geriatricians. Critical gaps in older patient’s care were identified, including the absence of dedicated care pathways, insufficient awareness of screening tools, and a need for enhanced professional training. Conclusions Tailored protocols and geriatric educational programs are crucial for improving the quality of emergency care provided to older individuals. These measures might also help relieve the burden on the Emergency Departments, thereby potentially enhancing overall efficiency and ensuring better outcomes.

Abstract Background Reviews on Down syndrome do not or only marginally address the issue of kidney and urogenital tract abnormalities, and lower urinary tract dysfunctions. Hence, we performed a meta-analysis of the literature. Methods A literature search was undertaken in the Library of Medicine, Web of Science and Excerpta Medica. The search algorithm combined various keywords: (Down syndrome OR trisomy 21 OR mongolism) AND (kidney OR urinary tract OR bladder) AND (malformation OR dysfunction OR anomaly OR abnormality OR size). The Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement was used. Results Eight case-control studies were retained for the final analysis. Three studies addressed the prevalence of kidney and urogenital tract abnormalities: an increased pooled relative risk of 5.49 (95%-CI: 1.78–16.93) was observed in Down syndrome. Penile malformations, obstructive malformations (including urethral valves), dilated urinary tract system, and kidney hypodysplasia were especially common. Three reports addressed the prevalence of lower urinary tract dysfunction: an increased pooled relative risk of 2.95 (95%-CI: 1.15–7.56) was observed. Finally, an autoptic study and an ultrasound study disclosed a reduced kidney size in Down syndrome. Conclusions This meta-analysis indicates that abnormalities of the kidney and urogenital tract, lower urinary tract dysfunctions, and a reduced kidney size present with an increased frequency in individuals with Down syndrome.

Abstract The article continues a trajectory of studies performed in the last few years regarding the topic of the body in discourse and urban planning design (Bianchetti. in Bodies between space and design, Jovis, Berlin, 2020, Bianchetti. in “Spazi corpi politiche” dialogue with Simona Forti and Paola Viganò, Biennale Democrazia, Turin, 25 March, Teatro Gobetti, 2023a, Bianchetti. in Le mura di Troia. Lo spazio ricompone i corpi. Donzelli, Rome, 2023b). It takes three books as its focus. The authors are: Colin Rowe and Dennis Hardy, Anthony Vidler, and Antoine Picon. I am personally very attached to these three books and believe they can help understand three different forms of the relationship between spaces and bodies. These forms of the relationship, respectively concern: the recomposition of bodies in space; the transfiguration of space that becomes projection of the neuroses and phobias of those who inhabit it; the tension between materiality and disembodiment. Recomposition, transfiguration, and disembodiment are ways in which spaces and bodies relate to each other. They speak of vulnerability, but also of the power of the body-in-space. The underlying question is: to what extent are urban planning policies and designs able to grasp the irreducibility of bodies? To what extent are they able to overcome the dedifferentiation that has created them for so long? Recomposition, transfiguration and disembodiment force us to reposition our attention beyond the ghost of a pure project, in the fallible and teeming kingdom of the relationships between bodies and spaces. The aim of the article is to highlight fragments of a critical discussion on design based on the complex relations between space, life, bodies and designs.

Abstract Introduction Worldwide, arterial hypertension is the foremost preventable and modifiable cardiovascular risk factor. In addition to lifestyle changes, recent international guidelines recommend single-pill, low-dose combinations as initial treatment strategy. We investigated whether this approach is feasible in a rural sub-Saharan Africa setting. Methods Diagnosis of hypertension was established over three sets of blood pressure measurements, performed according to the European Society of Hypertension recommendations by trained personnel, using a validated, automated, oscillometric device OMRON M7 IT-HEM-7322-E. In 98 individuals with arterial hypertension, a once-daily, single-pill combination of olmesartan, amlodipine, and hydrochlorothiazide was prescribed at an appropriate dose. Patients were instructed on its administration and potential side effects and encouraged towards lifestyle modifications. The treatment regimen was adjusted, if needed, at each outpatient clinic scheduled after 4, 8, 12, and 16 weeks. Results Seventy-nine patients (aged 61 [53–70] years; median and interquartile range) strictly adhered to the treatment schedule, while 19 individuals (70 [65–80] years) dropped out. Blood pressure was

Background. In high-income countries, shopping for non-prescription multivitamin–multimineral supplements has tremendously increased. Objective and Methods. The purpose of this labeling analysis is to inform on the daily elemental iron (with or without vitamin C) supply provided by multivitamin–multimineral supplements sold online by Amazon in Western and Southern Europe (amazon.es®, amazon.de®, amazon.it®, and amazon.fr®). Results. We identified 298 iron-containing multivitamin–multimineral preparations sold by Amazon marketplaces: 153 preparations sourced from amazon.de®, 68 from amazon.fr®, 54 from amazon.it®, and 23 from amazon.es®. The daily iron dose provided by these preparations was 14 [5–14] mg (median and interquartile range), with no differences among the marketplaces. Approximately 90% (n = 265) of the preparations contained ferrous iron. Moreover, 85% (n = 253) of the preparations were fortified with vitamin C in a dose of 80 [40–100] mg daily. Conclusions. The median supply of iron (about 14 mg) and vitamin C (80 mg) in iron-containing multivitamin–multimineral preparations offered on Amazon platforms in Western and Southern Europe falls below that currently recommended for iron deficiency in review articles, namely 100 mg of iron and 500 mg of vitamin C per day. The iron supply of iron-containing multivitamin–multimineral preparations falls also below the dose of 30–60 mg advocated to prevent iron deficiency in menstruating women.

Various studies have sought to understand factors affecting low university retention rates of indigenous students. However, little is known about students who successfully complete undergraduate programs in STEM fields. This investigation, utilizing the life history approach, analyzed academic trajectories of 11 Mapuche graduates or near-graduates from such programs in south-central Chile. The analysis showed that students who were successful in obtaining degrees had experienced early participation in communities that encouraged an academic culture. These were constituted by their families, teachers, and friends, and participation occurred throughout their lives as they successfully negotiated their identities as indigenous and academically talented students.

The use of extracts rich in bioactive compounds is becoming increasingly common in the food, cosmetics, and pharmaceutical industries for the production of functional products. Araticum is a potential fruit to be analyzed due to its content of phenolic compounds, carotenoids and vitamins, with antioxidant properties. Therefore, this study aimed to investigate the effect of ultrasound on total phenolic compounds, total carotenoids, ascorbic acid, color, turbidity and rheology in araticum juice. Response surface methodology based on a central composite design was applied. Araticum juice was subjected to sonication at amplitude levels ranging from 20 to 100 % of the total power (400 W) at a constant frequency of 20 kHz for different durations (2 to 10 min). Morphological analysis was conducted to observe microscopic particles, and viscosity and suitability to rheological models (Newtonian, Power Law, and Herschel-Bulkley) were assessed. The ultrasonic probe extraction method was compared to the control juice. According to the responses, using the desirability function, the optimal conditions for extraction were determined to be low power (low amplitude) applied in a short period of time or low power applied in a prolonged time. These conditions allowed an ultrasonic probe to act on releasing bioactive compounds without degrading them. All three rheological models were suitable, with the Power Law model being the most appropriate, exhibiting non-Newtonian pseudoplastic behavior.

Background Valproic acid is prescribed for epilepsy and as prophylaxis for bipolar disorder and migraine headaches. It has also been implicated as a cause of a kidney tubular injury. Methods We undertook a review of the literature to characterize the biochemical and histopathological features of the overt kidney tubular injury and to evaluate the possible existence of a pauci-symptomatic injury. The pre-registered review (CRD42022360357) was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. Searches were conducted in Excerpta Medica, the National Library of Medicine, and Web of Science. The gray literature was also considered. Results For the final analysis, we retained 36 articles: 28 case reports documented 48 individuals with epilepsy on valproic acid for 7 months or more and presenting with features consistent with an overt kidney tubular injury. The following disturbances were noted: hypophosphatemia (N = 46), normoglycemic glycosuria (N = 46), total proteinuria (N = 45), metabolic acidosis (N = 36), hypouricemia (N = 27), tubular proteinuria (N = 27), hypokalemia (N = 23), and hypocalcemia (N = 8). A biopsy, obtained in six cases, disclosed altered proximal tubular cells with giant and dysmorphic mitochondria. Eight case series addressed the existence of a pauci- or even asymptomatic kidney injury. In the reported 285 subjects on valproic acid for 7 months or more, an isolated tubular proteinuria, mostly N-acetyl-[beta]-glucosaminidase, was often noted. Conclusions Valproic acid may induce an overt kidney tubular injury, which is associated with a proximal tubular mitochondrial toxicity. Treatment for 7 months or more is often associated with a pauci- or oligosymptomatic kidney tubular injury. Graphical abstract, Author(s): Giulia Anguissola [sup.1] , Dennis Leu [sup.2] , Giacomo D. Simonetti [sup.1] [sup.2] , Barbara Goeggel Simonetti [sup.1] [sup.2] [sup.3] , Sebastiano A. G. Lava [sup.4] [sup.5] , Gregorio [...]

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration.

The rising obesity epidemic requires effective and sustainable weight loss intervention strategies that take into account both of individual preferences and environmental impact. This study aims to develop and evaluate the effectiveness of an innovative digital biohacking approach for dietary modifications in promoting sustainable weight loss and reducing carbon footprint impact. A pilot study was conducted involving four participants who monitored their weight, diet, and activities over the course of a year. Data on food consumption, carbon footprint impact, calorie intake, macronutrient composition, weight, and energy expenditure were collected. A digital replica of the metabolism based on nutritional information, the Personalized Metabolic Avatar (PMA), was used to simulate weight changes, plan, and execute the digital biohacking approach to dietary interventions. The dietary modifications suggested by the digital biohacking approach resulted in an average daily calorie reduction of 236.78 kcal (14.24%) and a 15.12% reduction in carbon footprint impact (−736.48 gCO2eq) per participant. Digital biohacking simulations using PMA showed significant differences in weight change compared to actual recorded data, indicating effective weight reduction with the digital biohacking diet. Additionally, linear regression analysis on real data revealed a significant correlation between adherence to the suggested diet and weight loss. In conclusion, the digital biohacking recommendations provide a personalized and sustainable approach to weight loss, simultaneously reducing calorie intake and minimizing the carbon footprint impact. This approach shows promise in combating obesity while considering both individual preferences and environmental sustainability.

Polyphenols are a class of natural compounds that act as antioxidants, neutralising harmful free radicals that would damage cells and increase the risk of diseases such as cancer, diabetes and heart disease. They also reduce inflammation, which is thought to be at the root of many chronic diseases.We are investigating the photoprotective effects of punicalagin, a type of polyphenolic compound mainly found in pomegranates, against UVA-induced damage in human skin fibroblasts. Punicalagin increases cell viability and reduces the high levels of ROS generated by photooxidative stress through its ability to modulate the Nrf2 transcriptional pathway. Interestingly, activation of the Nrf2 pathway results in an increase in reduced glutathione, NADH, and subsequently protects mitochondrial respiratory capacity. Integrating molecular and imaging approaches, our results demonstrate a potential cytoprotective effect of punicalagin against UVA-induced skin damage through an anti-apoptotic mechanism.