Drought-Adapted Mediterranean Diet Plants: A Source of Bioactive Molecules Able to Give Nutrigenomic Effects per sè or to Obtain Functional Foods.

The Mediterranean diet features plant-based foods renowned for their health benefits derived from bioactive compounds. This review aims to provide an overview of the bioactive molecules present in some representative Mediterranean diet plants, examining their human nutrigenomic effects and health benefits as well as the environmental advantages and sustainability derived from their cultivation. Additionally, it explores the facilitation of producing fortified foods aided by soil and plant microbiota properties. Well-studied examples, such as extra virgin olive oil and citrus fruits, have demonstrated significant health advantages, including anti-cancer, anti-inflammatory, and neuroprotective effects. Other less renowned plants are presented in the scientific literature with their beneficial traits on human health highlighted. Prickly pear's indicaxanthin exhibits antioxidant properties and potential anticancer traits, while capers kaempferol and quercetin support cardiovascular health and prevent cancer. Oregano and thyme, containing terpenoids like carvacrol and γ-terpinene, exhibit antimicrobial effects. Besides their nutrigenomic effects, these plants thrive in arid environments, offering benefits associated with their cultivation. Their microbiota, particularly Plant Growth Promoting (PGP) microorganisms, enhance plant growth and stress tolerance, offering biotechnological opportunities for sustainable agriculture. In conclusion, leveraging plant microbiota could revolutionize agricultural practices and increase sustainability as climate change threatens biodiversity. These edible plant species may have crucial importance, not only as healthy products but also for increasing the sustainability of agricultural systems.

Feasibility of Ultra-Low Volume Contrast-Saline Mixture Injection With Dual-Flow Technique in a Pre-TAVI Computed Tomography Angiography.

BACKGROUND: To explore the feasibility and image quality of ultra-low volume contrast-saline mixture injection with dual-flow injection technique in a computed tomography angiography (CTA) protocol in patients scheduled for transcatheter aortic valve implantation (TAVI). METHODS: Forty (40) TAVI candidates underwent investigation with CTA using a third-generation dual-source CT scanner between September and November 2020. Different volumes of a monophasic contrast-saline mixture at an 80:20 ratio were administered at an infusion rate of 3 mL/s in 20 patients (group A). The injected volume was based on patient body mass index (BMI): 50 mL if BMI <29 kg/m2 and 63 mL if BMI >29 kg/m2. The other 20 patients (group B)-the control cases-received a total of 65 mL of contrast medium (CM), in multiphasic injections at different flow rates, followed by 10 mL of saline. The images that were obtained were prospectively evaluated for image quality, vessel attenuation (HU), signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and estimated radiation dose. RESULTS: Image quality of the aortic root and ilio-femoral vessels was diagnostic in all patients. Vascular attenuation was >200 HU and CNR >3 at any vessel level. CONCLUSIONS: Data from this study suggest that a monophasic ultra-low volume contrast-saline mixture injection with a dual-flow technique can provide clear visualisation of the aortic root and ilio-femoral vessels in pre-TAVI CTA, which is comparable with a standard multiphasic volume injection protocol.

Streptomyces coelicolor Vesicles: Many Molecules To Be Delivered.

Streptomyces coelicolor is a model organism for the study of Streptomyces, a genus of Gram-positive bacteria that undergoes a complex life cycle and produces a broad repertoire of bioactive metabolites and extracellular enzymes. This study investigated the production and characterization of membrane vesicles (MVs) in liquid cultures of S. coelicolor M145 from a structural and biochemical point of view; this was achieved by combining microscopic, physical and -omics analyses. Two main populations of MVs, with different sizes and cargos, were isolated and purified. S. coelicolor MV cargo was determined to be complex, containing different kinds of proteins and metabolites. In particular, a total of 166 proteins involved in cell metabolism/differentiation, molecular processing/transport, and stress response were identified in MVs, the latter functional class also being important for bacterial morpho-physiological differentiation. A subset of these proteins was protected from degradation following treatment of MVs with proteinase K, indicating their localization inside the vesicles. Moreover, S. coelicolor MVs contained an array of metabolites, such as antibiotics, vitamins, amino acids, and components of carbon metabolism. In conclusion, this analysis provides detailed information on S. coelicolor MVs under basal conditions and on their corresponding content, which may be useful in the near future to elucidate vesicle biogenesis and functions. IMPORTANCE Streptomycetes are widely distributed in nature and characterized by a complex life cycle that involves morphological differentiation. They are very relevant in industry because they produce about half of all clinically used antibiotics, as well as other important pharmaceutical products of natural origin. Streptomyces coelicolor is a model organism for the study of bacterial differentiation and bioactive molecule production. S. coelicolor produces extracellular vesicles that carry many molecules, such as proteins and metabolites, including antibiotics. The elucidation of S. coelicolor extracellular vesicle cargo will help us to understand different aspects of streptomycete physiology, such as cell communication during differentiation and response to environmental stimuli. Moreover, the capability of these vesicles for carrying different kinds of biomolecules opens up new biotechnological possibilities related to drug delivery. Indeed, decoding the molecular mechanisms involved in cargo selection may lead to the customization of extracellular vesicle content.

An extended catalogue of ncRNAs in Streptomyces coelicolor reporting abundant tmRNA, RNase-P RNA and RNA fragments derived from pre-ribosomal RNA leader sequences.

Streptomyces coelicolor is a model organism for studying streptomycetes. This genus possesses relevant medical and economical roles, because it produces many biologically active metabolites of pharmaceutical interest, including the majority of commercialized antibiotics. In this bioinformatic study, the transcriptome of S. coelicolor has been analyzed to identify novel RNA species and quantify the expression of both annotated and novel transcripts in solid and liquid growth medium cultures at different times. The major characteristics disclosed in this study are: (i) the diffuse antisense transcription; (ii) the great abundance of transfer-messenger RNAs (tmRNA); (iii) the abundance of rnpB transcripts, paramount for the RNase-P complex; and (iv) the presence of abundant fragments derived from pre-ribosomal RNA leader sequences of unknown biological function. Overall, this study extends the catalogue of ncRNAs in S. coelicolor and suggests an important role of non-coding transcription in the regulation of biologically active molecule production.

Topical cyclosporine hydrogel preparation: A new therapeutic option in the treatment of nail psoriasis.

Nail psoriasis is a chronic nail disorder that commonly affects psoriatic patients causing severe distress despite the limited body surface area. Treatments for nail psoriasis are limited, as nails are often difficult to treat with topical therapies, and among different systemic agents responses are unpredictable. We carried out a prospective study in order to analyze the effectiveness and tolerability of topical cyclosporine hydrogel ointment in nail psoriasis. Three patients, for a total of 44 nails, were treated with topical cyclosporine hydrogel ointment. All nails were evaluated, before starting the treatment, every 28 days and after 12 weeks of therapy, by the same dermatologists, through clinical and onychoscopic evaluations. The patients were also asked to assess on the compliance with product use. Complete response (CR) was observed in 2 of 3 patients; a partial response (PR) was observed in the other patient. Overall, 24 of 44 nails had CR and 20 had a PR. Cyclosporine hydrogel ointment has shown efficacy and safety in the treatment of nail psoriasis. The product has also been shown to be stable in composition, easy to apply and not discomfortable for the patient.

COVID-19 safety measures at the Radiology Unit of a Transplant Institute: the non-COVID-19 patient's confidence with safety procedures.

PURPOSE: To support the wellbeing of both patients and their families, our aim was to investigate the satisfaction of non-COVID in- and out-patients regarding safety measures implemented at our radiology unit of a transplant institute against COVID infection. MATERIALS AND METHODS: Over a five-month period, adult patients' feedback was obtained by a questionnaire on the fear of contracting COVID-19 during a radiology examination, the perceived delay in treatment, and the following safety measures implemented: modified schedules to limit the number of patients in the waiting area and to maximize social distancing; assistance by staff when visitors were not admitted; cleaning and disinfection of machines; mask wearing and hand hygiene of staff; and staff advice on hand hygiene and infection control precautions. RESULTS: Over a five-month period, our preliminary results (387 patients) showed general patient satisfaction (99.1%) with safety measures applied at our radiology unit. Patients were satisfied with distancing and assistance by staff (100%), cleaning and disinfection (91%), mask wearing and hand hygiene of the staff (97%), and staff advice (94%). There was some criticism of the perceived delay in treatment (7.3%) and in the scheduling of the waiting list (5.4%), with 5.4% fearing contracting the virus. Patients' awareness of safety measures and confidence in the hospital preparedness policy was perceived by all interviewers, and 100% appreciated being questioned. CONCLUSION: The feedback given by the non-COVID patient helps to measure the quality in health care, to improve the quality service, and to protect and satisfy more vulnerable patients, also during the COVID-19 pandemic.

Refractory palmo-plantar discoid lupus erythematosus successfully treated with mycophenolate mofetil: Unusual localization and literature review.

Palmo-plantar lesions in discoid lupus erythematosus (DLE) can be considered a very distinct rarity, generally refractory to conventional treatments. We present a 47-year-old African female patient with a 6-month clinical history of palm and soles erosions. Clinical examination revealed painful multiple, well defined, erosions with an erythematous and scaly central area and peripherical post-inflammatory hyperchromic border bilaterally distributed on the palmo-plantar surfaces. Pterygium inversum unguis involved all nails of both hands. Histological analysis and direct immunofluorescence study confirmed palmo-plantar DLE. Therapy with mycophenolate mofetil (MMF) was initiated with a progressive clearing of palmo-plantar lesions and a drastic reduction of pain. Therapy was well tolerated, neither side effects nor altered laboratory investigations were observed. Our case and literature review confirm that MMF may be an effective approach for the management of refractory palmo-plantar DLE with a safer profile than Azathioprine regarding adverse effects and cutaneous malignancies risk.

Bacterial metal nanoparticles to develop new weapons against bacterial biofilms and infections.

The widespread use of antibiotics has resulted in the outbreak and spread of antibiotic-resistant pathogens. Bacterial antibiotic resistance may develop at cellular and community levels. In the latter case, it is based on tolerance which implicates the shift from a free-living form of life (i.e., planktonic) to a sessile multi-stratified community (i.e., biofilm). Metal nanoparticles (MNPs) have been shown to be promising candidates as antimicrobial agents. MNPs are able to interact with and penetrate bacterial biofilms, thus, resulting effective antibiofilm compounds. Another interesting aspect is the possibility of using plants, fungi, yeasts, and bacteria to obtain biogenic MNPs (BMNP). Bacteria are able to grow in presence of many different toxic heavy metal ions thanks to different metal resistance gene clusters that allow a variety of biochemical counters (formation of harmless complexes, efflux, precipitation, reduction, etc.). The formation of BMNPs by bacterial cells could be, in most cases, just a consequence of metal detoxification mechanisms. This review focuses on BMNPs from bacterial origin that may represent a good source of compounds with a broad spectrum of activity against common Gram-positive and Gram-negative pathogens and bacterial biofilms thereof. In particular, the state of art on BMNP synthesis by bacteria is presented and potential applications in the fight against biofilm-associated infections and resistant pathogens are highlighted. In addition, critical aspects on BMNP bacterial synthesis and utilization are commented.Key points• New antimicrobials to fight antibiotic-resistant pathogens are urgently needed.• Biogenic metal nanoparticles can efficiently hit biofilm-forming pathogens.• Metal-nanoparticle composition could confer specific antibiofilm activity.

Prognostic and Predictive Biomarkers in Stage III Melanoma: Current Insights and Clinical Implications.

Melanoma is one of the most aggressive skin cancers. The 5-year survival rate of stage III melanoma patients ranges from 93% (IIIA) to 32% (IIID) with a high risk of recurrence after complete surgery. The introduction of target and immune therapies has dramatically improved the overall survival, but the identification of patients with a high risk of relapse who will benefit from adjuvant therapy and the determination of the best treatment choice remain crucial. Currently, patient prognosis is based on clinico-pathological features, highlighting the urgent need of predictive and prognostic markers to improve patient management. In recent years, many groups have focused their attention on identifying molecular biomarkers with prognostic and predictive potential. In this review, we examined the main candidate biomarkers reported in the literature.

A comparative effectiveness study of lipegfilgrastim in multiple myeloma patients after high dose melphalan and autologous stem cell transplant.

G-CSF administration after high-dose chemotherapy and autologous stem cell transplantation (ASCT) has been shown to expedite neutrophil recovery. Several studies comparing filgrastim and pegfilgrastim in the post-ASCT setting concluded that the two are at least equally effective. Lipegfilgrastim (LIP) is a new long-acting, once-per-cycle G-CSF. This multicentric, prospective study aimed to describe the use of LIP in multiple myeloma patients receiving high-dose melphalan and autologous stem cell transplantation (ASCT) and compare LIP with historic controls of patients who received short-acting agent (filgrastim [FIL]). Overall, 125 patients with a median age of 60 years received G-CSF after ASCT (80 patients LIP on day 1 post-ASCT and 45 patients FIL on day 5 post-ASCT). The median duration of grade 4 neutropenia (absolute neutrophil count [ANC] < 0.5 × 10 [9]/L) was 5 days in both LIP and FIL groups, whereas the median number of days to reach ANC ≥ 0.5 × 10 [9]/L was 10% lower in the LIP than in the FIL group (10 vs 11 days), respectively. Male sex was significantly associated with a faster ANC ≥ 0.5 × 10 [9] L response (p = 0.015). The incidence of FN was significantly lower in the LIP than in the FIL group (29% vs 49%, respectively, p = 0.024). The days to discharge after ASCT infusion were greater in patients with FN (p < 0.001). The study indicates that LIP had a shorter time to ANC recovery and is more effective than FIL for the prevention of FN in the ASCT setting.

Biogenic iron-silver nanoparticles inhibit bacterial biofilm formation due to Ag+ release as determined by a novel phycoerythrin-based assay.

Silver nanoparticles (Ag-NPs) can be considered as a cost-effective alternative to antibiotics. In the presence of Fe(III)-citrate and Ag+, Klebsiella oxytoca DSM 29614 produces biogenic Ag-NPs embedded in its peculiar exopolysaccharide (EPS). K. oxytoca DSM 29614 was cultivated in a defined growth medium-containing citrate (as sole carbon source) and supplemented with Ag+ and either low or high Fe(III) concentration. As inferred from elemental analysis, transmission and scanning electron microscopy, Fourier transform infrared spectrometry and dynamic light scattering, Ag-EPS NPs were produced in both conditions and contained also Fe. The production yield of high-Fe/Ag-EPS NPs was 12 times higher than the production yield of low-Fe/Ag-EPS NPs, confirming the stimulatory effect of iron. However, relative Ag content and Ag+ ion release were higher in low-Fe/Ag-EPS NPs than in high-Fe/Ag-EPS NPs, as revealed by emission-excitation spectra by luminescent spectrometry using a novel ad hoc established phycoerythrin fluorescence-based assay. Interestingly, high and low-Fe/Ag-EPS NPs showed different and growth medium-dependent minimal inhibitory concentrations against Staphylococcus aureus ATCC 29213 and Pseudomonas aeruginosa ATCC 15442. In addition, low-Fe/Ag-EPS NPs exert inhibition of staphylococcal and pseudomonal biofilm formation, while high-Fe/Ag-EPS NPs inhibits staphylococcal biofilm formation only. Altogether, these results, highlighting the different capability of Ag+ release, support the idea that Fe/Ag-EPS NPs produced by K. oxytoca DSM 29614 can be considered as promising candidates in the development of specific antibacterial and anti-biofilm agents.Key points • Klebsiella oxytoca DSM 29614 produces bimetal nanoparticles containing Fe and Ag.• Fe concentration in growth medium affects nanoparticle yield and composition.• Phycoerythrin fluorescence-based assay was developed to determine Ag+release.• Antimicrobial efficacy of bimetal nanoparticle parallels Ag+ions release.

Proof-of-Principle of a Cherenkov-Tag Detector Prototype.

In a recent paper, the authors discussed the feasibility study of an innovative technique based on the directionality of Cherenkov light produced in a transparent material to improve the signal to noise ratio in muon imaging applications. In particular, the method was proposed to help in the correct identification of incoming muons direction. After the first study by means of Monte Carlo simulations with Geant4, the first reduced scale prototype of such a detector was built and tested at the Department of Physics and Astronomy "E. Majorana" of the University of Catania (Italy). The characterization technique is based on muon tracking by means of the prototype in coincidence with two scintillating tiles. The results of this preliminary test confirm the validity of the technique and stressed the importance to enhance the Cherenkov photons production to get a signal well distinguishable with respect to sensors and electronic noise.

Pyrrolomycins as antimicrobial agents. Microwave-assisted organic synthesis and insights into their antimicrobial mechanism of action.

New compounds able to counteract staphylococcal biofilm formation are needed. In this study we investigate the mechanism of action of pyrrolomycins, whose potential as antimicrobial agents has been demonstrated. We performed a new efficient and easy method to use microwave organic synthesis suitable for obtaining pyrrolomycins in good yields and in suitable amount for their in vitro in-depth investigation. We evaluate the inhibitory activity towards Sortase A (SrtA), a transpeptidase responsible for covalent anchoring in Gram-positive peptidoglycan of many surface proteins involved in adhesion and in biofilm formation. All compounds show a good inhibitory activity toward SrtA, having IC50 values ranging from 130 to 300 µM comparable to berberine hydrochloride. Of note compound 1d shows a good affinity in docking experiment to SrtA and exhibits the highest capability to interfere with biofilm formation of S. aureus showing an IC50 of 3.4 nM. This compound is also effective in altering S. aureus murein hydrolase activity that is known to be responsible for degradation, turnover, and maturation of bacterial peptidoglycan and involved in the initial stages of S. aureus biofilm formation.

Feasibility Study of a New Cherenkov Detector for Improving Volcano Muography.

Muography is an expanding technique for internal structure investigation of large volume object, such as pyramids, volcanoes and also underground cavities. It is based on the attenuation of muon flux through the target in a way similar to the attenuation of X-ray flux through the human body for standard radiography. Muon imaging have to face with high background level, especially compared with the tiny near horizontal muon flux. In this paper the authors propose an innovative technique based on the measurement of Cherenkov radiation by Silicon photo-multipliers arrays to be integrated in a standard telescope for muography applications. Its feasibility study was accomplished by means of Geant4 simulations for the measurement of the directionality of cosmic-ray muons. This technique could be particularly useful for the suppression of background noise due to back-scattered particles whose incoming direction is likely to be wrongly reconstructed. The results obtained during the validation study of the technique principle confirm the ability to distinguish the arrival direction of muons with an efficiency higher than 98% above 1 GeV. In addition, a preliminary study on the tracking performance of the presented technique was introduced.

An integrated proteomic and metabolomic study to evaluate the effect of nucleus-cytoplasm interaction in a diploid citrus cybrid between sweet orange and lemon.

KEY MESSAGE: Our results provide a comprehensive overview how the alloplasmic condition might lead to a significant improvement in citrus plant breeding, developing varieties more adaptable to a wide range of conditions. Citrus cybrids resulting from somatic hybridization hold great potential in plant improvement. They represent effective products resulting from the transfer of organelle-encoded traits into cultivated varieties. In these cases, the plant coordinated array of physiological, biochemical, and molecular functions remains the result of integration among different signals, which derive from the compartmentalized genomes of nucleus, plastids and mitochondria. To dissect the effects of genome rearrangement into cybrids, a multidisciplinary study was conducted on a diploid cybrid (C2N), resulting from a breeding program aimed to improve interesting agronomical traits for lemon, the parental cultivars 'Valencia' sweet orange (V) and 'femminello' lemon (F), and the corresponding somatic allotetraploid hybrid (V + F). In particular, a differential proteomic analysis, based on 2D-DIGE and MS procedures, was carried out on leaf proteomes of C2N, V, F and V + F, using the C2N proteome as pivotal condition. This investigation revealed differentially represented protein patterns that can be associated with genome rearrangement and cell compartment interplay. Interestingly, most of the up-regulated proteins in the cybrid are involved in crucial biological processes such as photosynthesis, energy production and stress tolerance response. The cybrid differential proteome pattern was concomitant with a general increase of leaf gas exchange and content of volatile organic compounds, highlighting a stimulation of specific pathways that can be related to observed plant performances. Our results contribute to a better understanding how the alloplasmic condition might lead to a substantial improvement in plant breeding, opening new opportunities to develop varieties more adaptable to a wide range of conditions.

A Comparative Assessment of Quality of Life in Patients with Multiple Myeloma Undergoing Autologous Stem Cell Transplantation Through an Outpatient and Inpatient Model.

Outpatient autologous stem cell transplantation (ASCT) has proven to be feasible in terms of physical morbidity and mortality outcomes, but little data exist on the impact of this procedure on quality of life (QoL). The purpose of this prospective, observational, longitudinal cohort study was to compare the effects of inpatient (n = 76) and outpatient (n = 64) modes of care on QoL in patients with multiple myeloma who underwent ASCT. Patients were treated according to their preference for the inpatient or outpatient model. QoL was assessed using the Functional Assessment of Cancer Therapy-Bone Marrow Transplantation (FACT-BMT) at baseline (7 days before ASCT; T1) and at days +7 (T2) and +30 (T3) after ASCT. Overall, inpatients achieved higher mean values at each time point (86.05 ± 15.54 at T1, 89.23 ± 19.19 at T2, and 87.96 ± 13.6 at T3) compared with outpatients (85.62 ± 14.51 at T1, 87.42 ± 23.41 at T2, and 83.98 ± 20.2 at T3), although the differences did not reach statistical significance. Inpatients showed higher mean scores than outpatients in physical well-being (7.67 ± 5.7, 15.44 ± 6.34, and 12.96 ± 6.03, respectively, versus 5.89 ± 4.33, 13.92 ± 7.05, and 8.84 ± 6.33, respectively; P < .05). Mean scores on social/family well-being were significantly higher in the outpatient group compared with the inpatient group (22.93 ± 13.29, 21.14 ± 5.31, and 21.64 ± 4.58, respectively, versus 20.59 ± 3.79, 19.52 ± 5.12, and 20.01 ± 3.97, respectively; P = .003). There were no significant between-group differences with respect to functional well-being and emotional status. Among adults at a single institution undergoing ASCT for MM, the use of outpatient care compared with standard transplantation care did not result in improved QoL during transplantation. Further research is needed for replication and to assess longer-term outcomes and implications.

Pirin: A novel redox-sensitive modulator of primary and secondary metabolism in Streptomyces.

Pirins are evolutionarily conserved iron-containing proteins that are found in all kingdoms of life, and have been implicated in diverse molecular processes, mostly associated with cellular stress. In the present study, we started from the evidence that the insertional inactivation of pirin-like gene SAM23877_RS18305 (pirA) by ΦC31 Att/Int system-based vectors in spiramycin-producing strain Streptomyces ambofaciens ATCC 23877 resulted in marked effects on central carbon and energy metabolism gene expression, high sensitivity to oxidative injury and repression of polyketide antibiotic production. By using integrated transcriptomic, proteomic and metabolite profiling, together with genetic complementation, we here show that most of these effects could be traced to the inability of the pirA-defective strain to modulate beta-oxidation pathway, leading to an unbalanced supply of precursor monomers for polyketide biosynthesis. Indeed, in silico protein-protein interaction modeling and in vitro experimental validation allowed us to demonstrate that PirA is a novel redox-sensitive negative modulator of very long-chain acyl-CoA dehydrogenase, which catalyzes the first committed step of the beta-oxidation pathway.

Genomic traits of Klebsiella oxytoca DSM 29614, an uncommon metal-nanoparticle producer strain isolated from acid mine drainages.

BACKGROUND: Klebsiella oxytoca DSM 29614 - isolated from acid mine drainages - grows anaerobically using Fe(III)-citrate as sole carbon and energy source, unlike other enterobacteria and K. oxytoca clinical isolates. The DSM 29614 strain is multi metal resistant and produces metal nanoparticles that are embedded in its very peculiar capsular exopolysaccharide. These metal nanoparticles were effective as antimicrobial and anticancer compounds, chemical catalysts and nano-fertilizers. RESULTS: The DSM 29614 strain genome was sequenced and analysed by a combination of in silico procedures. Comparative genomics, performed between 85 K. oxytoca representatives and K. oxytoca DSM 29614, revealed that this bacterial group has an open pangenome, characterized by a very small core genome (1009 genes, about 2%), a high fraction of unique (43,808 genes, about 87%) and accessory genes (5559 genes, about 11%). Proteins belonging to COG categories "Carbohydrate transport and metabolism" (G), "Amino acid transport and metabolism" (E), "Coenzyme transport and metabolism" (H), "Inorganic ion transport and metabolism" (P), and "membrane biogenesis-related proteins" (M) are particularly abundant in the predicted proteome of DSM 29614 strain. The results of a protein functional enrichment analysis - based on a previous proteomic analysis - revealed metabolic optimization during Fe(III)-citrate anaerobic utilization. In this growth condition, the observed high levels of Fe(II) may be due to different flavin metal reductases and siderophores as inferred form genome analysis. The presence of genes responsible for the synthesis of exopolysaccharide and for the tolerance to heavy metals was highlighted too. The inferred genomic insights were confirmed by a set of phenotypic tests showing specific metabolic capability in terms of i) Fe2+ and exopolysaccharide production and ii) phosphatase activity involved in precipitation of metal ion-phosphate salts. CONCLUSION: The K. oxytoca DSM 29614 unique capabilities of using Fe(III)-citrate as sole carbon and energy source in anaerobiosis and tolerating diverse metals coincides with the presence at the genomic level of specific genes that can support i) energy metabolism optimization, ii) cell protection by the biosynthesis of a peculiar exopolysaccharide armour entrapping metal ions and iii) general and metal-specific detoxifying activities by different proteins and metabolites.

Bone Geometry, Quality, and Bone Markers in Children with Type 1 Diabetes Mellitus.

Adults with Type 1 diabetes mellitus show a high risk of bone fracture, probably as a consequence of a decreased bone mass and microarchitectural bone alterations. The aim of the study was to investigate the potential negative effects of type 1 diabetes on bone geometry, quality, and bone markers in a group of children and adolescents. 96 children, mean age 10.5 ± 3.1 years, agreed to participate to the study. Bone geometry was evaluated on digitalized X-rays at the level of the 2nd metacarpal bone. The following parameters were investigated and expressed as SDS: outer diameter (D), inner diameter (d), cortical area (CA), and medullary area (MA). Bone strength was evaluated as Bending Breaking Resistance Index (BBRI) from the geometric data. Bone turnover markers (PINP, CTX-I, and BAP), sclerostin, Dkk-1, PTH, and 25OH-Vitamin D were also assessed. A group of healthy 40 subjects of normal body weight and height served as controls for the bone markers. D (- 0.99 ± 0.98), d (- 0.41 ± 0.88), CA (- 0.85 ± 0.78), and MA (- 0.46 ± 0.78) were all significantly smaller than in controls (p < 0.01). BBRI was significantly lower (- 2.61 ± 2.18; p < 0.0001). PTH, PINP, and BAP were higher in the diabetic children. Multiple regression analysis showed that CA and D were influenced by insulin/Kg/day and by BMI, while d was influenced by PINP only. Type 1 diabetic children show smaller and weaker bones. The increased bone turnover could play a key role since it might amplify the deficit in bone strength associated with the inadequate osteoblastic activity caused by the disease itself.

Venoocclusive disease due to chemotherapy for pediatric acute lymphoblastic leukemia is associated with increased levels of plasminogen-activator inhibitor-1.

We describe three cases of sinusoidal obstruction syndrome/venoocclusive disease (SOS) in pediatric patients with acute lymphoblastic leukemia (ALL). All three episodes occurred during or just after the induction or reinduction phase of treatment based on prednisone/dexamethasone, vincristine, daunorubicin, and pegylated-l-asparaginase. SOS episodes were categorized as mild/moderate and resolved in 7, 10, and 16 days using supportive measures or defibrotide therapy. In all three episodes, the clinical diagnosis of SOS was associated with a significant increase in plasminogen-activator inhibitor-1 (PAI-1) that reduced with patient clinical improvement. PAI-1 warrants study as a diagnostic marker for SOS in ALL.