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Bivalve aquaculture is an important and rapidly expanding sector in global food production, yet climate change presents numerous challenges to its continued expansion. The Atlantic surfclam Spisula solidissimais emerging as an attractive alternate species for aquaculturists across the northeastern United States since it is native, grows rapidly, and complements the region’s established farming framework. However, the species is vulnerable to prolonged high temperature conditions, an issue that will be exacerbated by rising ocean temperatures and is particularly problematic on shallow coastal farms. In this study, we evaluated the response of adult farmed Atlantic surfclams to heat stress after juvenile exposure and the ability for heat tolerance to be passed to subsequent generations. We found that when juvenile Atlantic surfclams were exposed to prolonged lethal temperatures, the adult survivors withstood subsequent heat stress for significantly longer than individuals not exposed to lethal temperatures as juveniles. We also found that selective breeding enhanced heat tolerance in first‐generation Atlantic surfclam progeny. Moreover, growth of the heat‐selected progeny was not significantly different from that of control Atlantic surfclams. Although more research on this topic is necessary, this work suggests that selective breeding may be a viable strategy for enhancing survival of cultivated bivalves vulnerable to heat stress.

ABSTRACTThis present work focuses on the mapping of marbles, decorative patterns and area of the mosaics of the St. Nicola’s Basilica in Bari (Italy) by their photogrammetric survey. The extraordinary importance of these mosaics is due to the stylistic uniqueness and the undisputed workmanship and to the employed materials for tesserae. These mosaics include the white and polychrome marbles, used in the Roman age and reused in medieval artistic production, and imitation stones used as substitutes during the past restorations. The digital survey was realised by the photogrammetric reconstruction of mosaics collecting a photo dataset, after the mosaics redrawing by an image processing software and finally implemented it with lithological identification marbles. It allowed to obtain a punctual mapping of materials, through which to identify original areas and restoration areas, decorative patterns, recurring geometries. The research carried out, supported by the photogrammetric reconstruction as established method for high resolution digital reproduction and mapping, not only ensures the conservation and improvement of the enjoyment of the mosaic floors of the St. Nicola’s Basilica, but allows to conduct studies on materials, decorative patterns and restoration areas directly on the digitized product.

Laparoscopic liver resection (LLR) is becoming standard practice, replacing the open approach in terms of safety and feasibility. However, few data are available for the elderly. The objective of this study is to assess the feasibility of LLR in elderly patients, by making a comparison with open liver resection (OLR) and with non-elderly patients. Relevant studies found in the Cochrane Library, Embase, PubMed, and Web of Science were used in order to perform a systematic review and meta-analysis. Nine fully extracted comparative studies were included and two groups were identified: Group 1 with a comparison between OLR and LLR in the elderly and Group 2 with a focus on differences after LLR between elderly and non-elderly patients. A total number of 497 elderly patients who underwent LLR were analyzed. A random effect model was used for the meta-analysis. In Group 1, 1025 elderly patients were included: 640 underwent OLR and 385 underwent LLR. LLR was associated with minor blood loss (MD − 240 mL, 95% CI − 416.61, − 63.55; p0.008; I2= 96%), less transfusion (8% vs. 13.1%; RR 0.61, 95% CI 0.41, 0.91; p= 0.02; I2= 0%), fewer postoperative Clavien-Dindo III/IV complications (RR 0.48 in favor of LLR; 95% CI 0.29, 0.77; p= 0.003; I2= 0%). On the other hand, no significant difference was observed in terms of bile leakage, ascites, mortality, liver failure, or R0 resection. Group 2 included 112 elderly and 276 non-elderly patients who underwent LLR. The meta-analysis showed no significant difference in terms of blood loss, transfusions, liver failure, Clavien-Dindo III/IV complications, postoperative mortality, ascites, bile leak, hospital stay, R0 resection, and operative time. Laparoscopic liver resection is a safe and feasible procedure for elderly patients. However, further randomized studies are required to confirm this.

ABSTRACTThis paper focuses on the use of the photogrammetric method to obtain 3D model of artworks for their characterisation and conservation. The high-resolution reproduction of a piece of art allows both the identification of constituent materials, decorative elements and detailed features and its digitalisation and enjoyment and then enhancement. In this study the approach was applied to the polychrome marble altars in the crypt of the St. Sabino’s cathedral and in the St. Giacomo’s church, both in Bari (Italy), significant evidences of virtuosity of Baroque sculptors and of use and reuse of precious Roman marbles combined with more recent and local stones. For this purpose, firstly, a three-dimensional model and high definition survey were performed by collection of numerous photographs and their processing using photogrammetric method and digital survey software; in addition, identification of Roman marbles and other decorative stones was carried out in terms of lithological classification, provenance locality, the historical period of employ. Results, obtained through an inexpensive, fast and complete survey, allowed to produce a high definition representation of the altars for a complete mapping of used material and decorative features and to guarantee their conservation, sharing and enhancement.

Beach sands from the Rosa Marina locality (Adriatic coast, southern Italy) were analysed mainly microscopically in order to trace the source areas of their lithoclastic and bioclastic components. The main cropping out sedimentary units were also studied with the objective to identify the potential source areas of lithoclasts. This allowed to establish how the various rock units contribute to the formation of beach sands. The analysis of the bioclastic components allows to estimate the actual role of organisms regarding the supply of this material to the beach. Identification of taxa that are present in the beach sands as shell fragments or other remains was carried out at the genus or family level. Ecological investigation of the same beach and the recognition of sub-environments (mainly distinguished on the basis of the nature of the substrate and of the water depth) was the key topic that allowed to establish the actual source areas of bioclasts in the Rosa Marina beach sands. The sedimentological analysis (including a physical study of the beach and the calculation of some statistical parameters concerning the grain-size curves) shows that the Rosa Marina beach is nowadays subject to erosion.

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The Atlantic surfclam (Spisula solidissima) is a promising candidate for species diversification in the United States Northeast because it is native, grows rapidly, and is relatively recognizable to the public. However, gaps in the surfclam husbandry literature have left aquaculture practitioners without a complete understanding of how to best cultivate this species on commercial scales. In particular, relatively few studies have examined which culture conditions are necessary for rearing juvenile surfclams during the nursery phase. To fill this gap, controlled experiments were conducted to evaluate the efficacy of various gear types that are commonly used to rear other juvenile bivalve species. Specifically, growth and survival of early juvenile surfclams (0.4–2.7 mm) were compared when reared in different gear combinations, including downwellers, upwellers, and bell siphon systems. Similarly, growth and survival of late juvenile surfclams (1.1–18.0 mm) were compared when reared in upwellers and shallow raceways, with and without sand. Sediment accumulation, a proxy for culture cleanliness and system maintenance, was also monitored during the late nursery experiment. Results indicate that multiple rearing methods can effectively produce commercial-scale quantities of surfclams, but flow rate, food availability, and temperature are important factors that can limit gear efficiency. All early nursery gear systems performed similarly, while the late nursery upweller system performed significantly better than both types of shallow raceway systems. This study reinforces the feasibility of surfclams as a culture species that aligns well with the Northeast’s established shellfish farming framework.

This study focuses on defining compositional and structural characteristics, identifying raw materials and production technology, and validating the archaeological hypothesis of a local production of thin-walled pottery (2ndcent. BC–3rdcent. AD) in the Vesuvian area. Samples investigated were analysed using OM, SEM-EDS, XRD and LA-ICPMS supported by a statistical multivariate treatment of the compositional data of the ceramic bodies. The results obtained show how an integrated approach of analytical techniques can provide answers to archaeological questions and also give a valuable insight into the exchange of raw materials and/or finished products between sites. The paper also discloses how a combined analytical methodology represents a positive step in answering the one question which remains unsolved concerning the entire ceramic production in the Vesuvian area: the provenance of the clayey raw materials used. Indeed, the massive pottery production in the Bay of Naples down the ages contrasts with the unavailability of the necessary clayey local resources.

AbstractWe report the case of a boy affected by severe intrauterine and postnatal growth retardation, microcephaly, facial dysmorphisms and postnecrotic cirrhosis, diagnosed at birth as having Seckel syndrome, and subsequently confirmed as Majewski osteodysplastic primordial dwarfism type II (MOPD II) on the basis of clinical and radiological features of skeletal dysplasia. At our observation (6 years 7 months) he presented height –10.3 standard deviation score (SDS), weight –22.1 SDS, head circumference –8 SDS, delayed bone age of 4 years with respect to chronological age. In consideration of the low levels of insulin-like growth factor-1 (IGF-1) as well as of hepatic insufficiency, we started the treatment with recombinant human IGF-1 (rhIGF-1) at the dose of 0.04 mg/kg in 2 doses/day, with an increase of 0.04 mg/kg after 1 week until the maximum dose of 0.12 mg/kg. We observed an early response to rhIGF-1 treatment, with a shift of height velocity from 1.8 cm/year (–4.6 SDS) at 4 cm/year (–1.9 SDS), and an increase in bone age of 1.5 years during the first 6 months. rhIGF-1 treatment does not seem to be able to replace the physiological action of IGF-1 in patients with MOPD II and hepatic insufficiency, however, it seems to preserve the typical growth pattern of MOPD II patients, avoiding a further widening of the growth deficiency in these subjects.

Glucuronidation is an important metabolic process of detoxification in all vertebrates. The reaction is catalyzed by a multigene family of UDP-glucuronosyltransferases (UGTs) able to convert many xenobiotics and endobiotics (hydrophobic substances) to inactive, water-soluble glucuronides. The UGTs play a protective role, facilitating the elimination of potentially toxic metabolites via urine, bile and feces; therefore, impairment of UGTs may have important toxicological consequences. The regulation of UGTs during bacterial infection or inflammation is not well described. In this study, we investigated the in vitro effect of lipopolysaccharide (LPS) on the expression of the UGT1A6 isoform in human colon carcinoma Caco-2 cells. Results demonstrated a significant down-regulation of UGT1A6 expression, both in terms of mRNA and protein levels, and a reduced UGT activity after LPS exposure of cell cultures, suggesting a role for endotoxins on UGT regulation mechanisms.

This study is focused on the links between the major products of inflammation and cell damage induced by the administration of lipopolysaccharide (LPS) from Salmonella typhimurium in embryonal cardiomyocytes. LPS treatment for 72 hours induced transcription factor NF-B activation, inducible nitric oxide synthase (iNOS) and cyclooxygenase (COX)-2 expression, nitric oxide (NO) and tumor necrosis factor (TNF)- release. Moreover, LPS administration induced a significant cell loss, reversed by the NO-synthases inhibitor, suggesting a relationship between cell damage and iNOS-dependent NO overproduction. Cell death was reversed by the specific NF-B inhibitor, TPCK, whereas COX-2 specific inhibitor determined an increase of cell damage in terms of apoptosis, as observed by YO-PRO immunostaining, DNA laddering analysis and caspase-3 activation. Overall these findings evidenced a selective role for NF-B in mediating NO-induced cell damage and a protective action by COX-2 in LPS-treated embryonal cardiomyocytes. The reflection of these experiments on human cardiac pathology will be discussed.

Random mutations of the first nucleotide of a coding triplet alter the hydropathic character of 27 % of the hydrophobic amino acids and of 23 % of the hydrophilic amino acids, while random mutations of the second nucleotide alter the hydropathic character of 82 % of the hydrophobic amino acids and of 47 % of the hydrophilic amino acids. In cases of a change of the hydropathic character, a second random mutation in the previously unmutated first or second nucleotide causes reversion to the original character of an additional 11 % of the originally hydrophobic-coding triplets and an additional 14 % of the originally hydrophilic-coding triplets (on average). Thus, a selection oriented towards the preservation of the hydropathic character of amino acids may be expected to eventually result in a higher conservation of the second nucleotide (as compared to the first). In the case of uncorrected mutations of one of the two first nucleotides, it may be expected that appropriate second mutations in the other unaffected nucleotide will be positively selected. This would result in a positive correlation between the conservation/mutation indexes of the two first nucleotides, as these would be prevailingly either both conserved or both mutated. We examined six groups of coding mRNA sequences: chemokine CXC 1 and 4 and formyl peptide receptors; a group comprising different receptors of the rhodopsin-like superfamily, together with some viral sequences which share significant homologies with these receptors; a group of viral sequences with homologies with the rhodopsin-like receptors; a group of solute carriers. In all the experimental groups the second nucleotide of the triplet was the most conserved and a significant positive correlation existed between conservation/mutation indexes of the two first nucleotides. Similar conservation/mutation patterns could be of more general occurrence in the genome, as a consequence of selection processes.

AbstractCraniopharyngioma is a rare, benign, suprasellar brain tumor associated with a significant number of endocrine and metabolic impairments. Growth hormone deficiency, caused by the tumor itself or by its subsequent surgical treatment, is the most common hormone deficiency in these patients and replacement is frequently necessary. Hypothalamic obesity observed after surgery treatment, whether combined with radiotherapy or not, presents with increased abdominal fat and altered lipid profiles and is likely caused by both disruption of the mechanisms controlling satiety, hunger and energy balance and impairment of sensitivity to leptin, insulin and ghrelin axis. It is well known that hyperlipemia is associated with acute pancreatitis, both as a precipitant and as an epiphenomenon. Moreover, the increased incidence of acute pancreatitis during growth hormone therapy is possibly due to increased enzyme production (e.g., amylase, lipase and elastase). We report the case of a 13-year-old girl affected by craniopharyngioma on growth hormone replacement treatment who developed acute pancreatitis. We suggest including routine evaluation of lipid profile during follow-up of all children on growth hormone treatment, especially those affected by hypopituitarism secondary to craniopharyngioma, given pancreatic adverse effects of growth hormone replacement therapy and associated metabolic impairment due to hypothalamic obesity.Copyright © 2008 S. Karger AG, Basel

Various proteins that are required for the building of new complete human immunodeficiency type 1 virions (HIV-1) are coded by unspliced or partly spliced virus-derived mRNAs. HIV-1 has developed special strategies for moving these mRNAs to the cytoplasm to be translated. In the nucleus of the infected cell the virus-derived protein Regulator of expression of viral proteins (Rev) can bind both the viral intron-containing mRNAs and the cellular co-factor HIV-1 Rev binding protein (HRB) and this complex may be shuttled through the nuclear pores. HRB genes have been relatively well conserved during evolution, from Drosophila to humans. However, as a consequence of reading-frame shifts due to nt insertions/deletions, the protein products generated may differ considerably from the prototypal HRB protein, which comprises one Arf-GAP zinc finger domain, several Phenylalanine-Glycine (FG) motifs and four Asparagine-Proline- Phenylalanine (NPF) motifs. This variability is best exemplified by four HRB proteins of the dog, which are discussed here in more detail. The hypothesis is advanced that atypical HRB proteins may not be able to bind Rev and possibly have other, still undetermined, functions. Since the cellular co-factor HRB is essential for viral replication and spread but is not required for cell viability and main bodily functions, it might be an attractive candidate for anti-HIV-1 drug targeting.

AbstractAims:To evaluate therapy and dose adjustments in patients with congenital hypothyroidism (CH), longitudinally followed up until 16 years old, according to aetiology, Beclard’s nuclei presence, and thyroxine (T4) level at diagnosis. Methods:L-T4/kg/day and dose change ratio (CR) were assessed in 74 CH patients. Results:The dose was statistically larger in athyreosis than in dyshormonogenesis (1–10 and beyond 14 years) and in ectopy (2, 15, 16 years). The ectopic children required statistically larger L-T4/kg than the dyshormonogenetic ones (3–7 years). The L-T4/kg/day was increased, not statistically, in patients or with T4 <30 nmol/l or without Beclard’s nuclei at diagnosis. The CR progressively dropped after the 6th month at each attendance, without any difference in terms of aetiology, T4 level at diagnosis, or Beclard’s nuclei. The total CR was greater (significantly) in patients without Beclard’s nuclei, and (not significantly) in those with T4 <30 nmol/l at diagnosis or with agenesia. Conclusion:The L-T4 dose in CH is highly affected by the aetiology. The CR is higher in patients with delayed bone maturation at diagnosis. We suggest that these latter patients need blood tests more frequently to obtain a proper titration of the therapy.Copyright © 2007 S. Karger AG, Basel

In this paper we analyze a 55-amino acid (aa) sequence which is relatively well conserved in several seventransmembrane receptor families (from Insects to Mammals) and in some Viruses. This sequence, which covers the second transmembrane domain, the first extracellular loop and the third transmembrane domain, appears in its complete configuration in most of the seven-transmembrane receptor families, as well as in the protein products of some viruses. Other seven-transmembrane receptors and viruses exhibit reduced configurations of the conserved sequence, lacking either aa 31 or aa 30-31. 53-aa configurations are typically found in most chemokine receptor (CKR) subfamilies, as well as in some viral protein products. However, the CCR1, CCR3, and CCR6 subfamilies comprise a 54-aa configuration and the CKRrelated protein products, ChemR23 and RDC1, include the complete 55-aa sequence. For each CKR subfamily the ”modal sequence” of the conserved segment was constructed by selecting the most frequently occurring aa at each position. Then, pairwise alignments were made between: (i) the modal CKR sequences, and (ii) the sequence (53-aa) of the Yaba-like disease virus - 7L protein. From the alignments two consensus matrices were derived: (i) the consensus 1 matrix with reference to the whole conserved segment, and (ii) the consensus 2 matrix with reference to aa 22-29, which appear to be the most variable segment of the sequence. Based on the obtained consensus values and with reference to this specific conserved segment, the following conclusions are proposed: (1) ChemR23 and RDC1 are probably the more primitive CKR forms; (2) CCR1 and CCR3 may be grouped in a single cluster; (3) CCRs 2, 4, and 5 are closely related to each other and may be grouped in a cluster; CCR7 is likely to be evolutionarily related to this cluster; (4) CXCRs 2, 3, and 4 and CCX CKR appear to be evolutionarily related to each other and very likely derived from an CCR6-like gene; (5) CCR2/4/5 and CCR7 may have derived either from CCR1/3-like or CCR6-like genes; (6). The Yaba-like disease virus - 7L protein most likely derived, through “molecular piracy”, from a CCR8-like gene. We also discuss possible, more remote, evolutionary links between CKRs, formylpeptide receptors, and possibly the highly conserved 18S rRNA genes.

We measured the final height (FH) of 25 short polytransfused thalassemia major (Th) patients (18 males) with a reduced GH reserve treated for 3.3±1.2 yr with recombinant GH (rhGH), 0.2 mg/kg/week sc. At baseline, all patients were clinically prepubertal; their chronological (CA) and bone ages (BA) were 13.6±2.0 and 11.4±1.6 yr, respectively. In 9 out of 18 males and 5 out of 7 females, the onset of puberty occurred spontaneously during the treatment. At the end of the rhGH administration, the height of the enrolled children was not significantly increased when calculated for CA (HxCA), while it was significantly decreased (p=0.004) when calculated for BA (HxBA); the BA increase (3.29±1.65 yr) was significantly higher (p<0.001 ) than the height age increase (2.16±0.98 yr). The FHxCA showed a significant increase (p=0.001) compared to both baseline and the end of therapy, while the FHxBA was significantly decreased (p<0.001) compared with the corresponding value at baseline. At the end of therapy, both HxCA and HxBA resulted positively related to the BA at baseline (r=0.50 and 0.42, p=0.012 and 0.034, respectively). FH was positively correlated with CA (r=0.63, p=0.001), BA (r=0.68, p<0.001) and HxBA (r=0.59, p=0.002) evaluated at baseline, and with both HxCA and HxBA (r=0.82 and 0.74, respectively, p<0.001), evaluated at the end of treatment. A negative correlation was found between FH and the length of treatment (r=−0.56, p=0.004). Our data seem to exclude that prolonged rhGH therapy could improve FH in Th patients; on the contrary, a negative effect may be hypothesized.

Nitric oxide (NO) is a pleiotropic mediator of numerous biological processes, including smooth muscle relaxation, neurotransmission and defence against pathogens. In addition, NO is involved in the pathogenesis and control of inflammation, tumors, autoimmunity, and infectious and chronic degenerative diseases. NO, a highly reactive radical, is produced from L-arginine and oxygen by the enzyme NO synthase (NOS). Three NOS isoforms have been identified: two distinct NOS isoforms are constitutively expressed in cells, whereas a third isoform, inducible NOS (iNOS), is transcribed in response to specific stimuli. In particular, iNOS is responsible for the discontinuous synthesis of high amounts of NO and was originally characterized in murine macrophages after exposure to cytokines and / or microbial products. A wide range of microorganisms is sensibly inhibited in its development by NO, like fungi, bacteria, protozoa and viruses. Although NO production and its antimicrobial effect appear well established in rodent macrophages, the existence of L-arginine pathway in human mononuclear phagocytes has long been disputed. Recently, evidences showing the iNOS activity and NO production in other animal models, including humans, are now emerging, even if the NO induction has been more difficult to demonstrate. The present observations provide evidence for the occurrence of iNOS protein expression and NO production in human macrophages cultured in vitro.

OBJECTIVE: Many studies have examined genetic factors associated with either development or severity of primary osteoarthritis (OA). Analyses of the frequencies of HLA antigens in various OA populations have yielded conflicting results; an increased frequency of HLA-A1, B8, and DR4 alleles has been suggested. We investigated the interrelationship between HLA antigens and primary OA. METHODS: We analyzed the frequency of HLA-A, B, C, DR, and DQ antigens in 95 patients (82 women, 13 men) with primary OA of the hands compared to 200 controls matched for age, sex, and ethnicity. Class I and Class II HLA antigens were evaluated using conventional serologic typing. RESULTS: No statistically significant difference in the distribution of HLA-A1 and B8 antigens was observed in patients with OA compared to controls. By contrast, HLA-B35, B40, DQ1, and CW4 antigens were overrepresented in the OA patients. Haplotype analysis showed an association of B35-DQ1, B40-DQ1, and DR2-DQ1 with increased OA risk. CONCLUSION: Our results suggest a role of the HLA system in the etiopathogenesis of primary OA of the hand.

Abstract.: Chemokines are a group of structurally defined small proteins that act as chemoattractants for leukocytes and are involved in many different biological activities, including leukocyte activation for antimicrobial mechanisms. We studied the effect of the chemokines monocyte chemotactic protein (MCP)-1 and macrophage inflammatory protein (MIP)-1α on nitric oxide release and parasitocidal ability of peripheral blood-derived human macrophages in vitro infected with Leishmania infantum, zymodeme MON1. In infected human macrophages, treatment with MCP-1 or MIP-1α significantly enhanced nitric oxide production and leishmanicidal ability, compared with untreated cells, to the same levels induced by interferon-γ. Both nitric oxide release and parasitocidal ability of macrophages were significantly reduced by addition of L-N Gmonomethylarginine (L-NMMA), which is a competitive inhibitor of the L-arginine nitric oxide pathway. These data suggest that MCP-1 and MIP-1α mediate macrophage activation for nitric oxide release and subsequent parasite clearance, and thus may play a role in the containment of Leishmania infection.

Abstract: Nitric oxide (NO), produced by the nitric oxide synthase (iNOS) enzyme, is the most-important molecule responsible for the killing of Leishmania parasites by macrophages. In previous work we have demonstrated that, after activation with recombinant human interferon-γ and/or bacterial lipopolysaccharide, human macrophages infected with Leishmania infantum are able to produce nitric oxide and to express nitric oxide synthase. The arachidonate derivative prostaglandin E2 has been shown to modulate various macrophage activities, and in particular nitric oxide production, sometimes with opposite effects, related to experimental conditions. In this work we have evaluated nitric oxide release and parasite killing by peripheral blood-derived L. infantum-infected human macrophages in vitro stimulated with lipopolysaccharide and simultaneously treated with prostaglandin E2. Experiments were also performed in the presence of the nitric oxide synthase inhibitor l-N G monomethylarginine (l-NMMA) and of the cyclooxygenase inhibitor indomethacin. Nitric oxide release in supernatants of macrophage cultures was measured by the Griess reaction for nitrites. Parasite killing was microscopically evaluated by fluorescent dyes. Results demonstrated that macrophages stimulated with lipopolysaccharide and treated with prostaglandin E2 exhibited increased nitric oxide producation and parasite killing, which were significantly reduced by either l-NMMA or indomethacin. In indomethacin-treated macrophages, nitric oxide production and leishmanicidal ability were partially restored by the addition of exogenous prostaglandin E2. Taken together, these results indicate that prostaglandin E2 may be involved in nitric oxide production, and possibly in the host-protective immune response against Leishmania. Moreover, the demonstration of a stimulatory role of prostaglandin E2 on nitric oxide production induced by intracellular pathogens in humans is interesting in the light of a possible pharmacological regulation of nitric oxide by modulation of prostaglandin E2 synthesis.

Treatment with recombinant growth hormone (rhGH), 0.6 IU/kg/week s.c., previously successfully conducted for one year, was continued in 15 (Group A) and 8 (Group B) short thalassemia major patients with reduced GH reserve, for two and three years, respectively. In Group A, height for chronological: age (Ht SDSca) increased significantly (p = 0.021) from the start of treatment, but the positive effect was only apparent because of the concomitant slight worsening of height for bone age (Ht SDSba). Median AHt SDScA/AHt SDSba was <1.0 with respect to both the start (0.87) and the end of the first year of rhGH therapy (0.89). IGF-I levels increased significantly (p = 0.043) compared with values both at the start and at the end of the first year of rhGH therapy. In Group B neither Ht SDSca : nor Ht SDSba differed statistically from starting values, the former having a positive trend and the latter a negative one. Median AHt SDScA/AHt SDSba was 0.92 with respect to the start, and 0.94 with respect to the end of the second year. IGF-I levels increased significantly (p = 0.043) with respect to starting values. Our data show that the encouraging results described from the first year of rhGH treatment did not persist during the second and third years, and we conclude that this is because increase in bone age with continued treatment is equal to, or slightly greater than the height age increase. We propose that patients with thalassemia major with short stature should receive rhGH treatment for only one year, and that more prolonged treatment should be reserved for selected adolescents who have psychological problems due to shortness; for these patients growth acceleration could represent the main goal, even if this leads to a substantially unchanged or slightly decreased final height.

Background: To assess the spectrum and frequency of modalities used for emergency room (ER) imaging and their findings in pediatric cancer patients and assess their relationship with survival. Methods: Consecutive pediatric cancer patients that underwent imaging during an ER visit at our tertiary cancer center over a 5-year period were retrospectively analyzed. Imaging findings were considered positive when they were relevant to the ER presenting complaint. Imaging positivity was correlated with inpatient admission. Overall survival (OS) was assessed with Kaplan-Meier curves and uni- and multi-variate Cox proportional hazards model was used to identify significant factors associated with OS. Results: Two hundred sixty-one patients (135 males and 126 females; median age 11 years [interquartile range 5–16 years] with 348 visits and a total of 406 imaging studies were included. Common chief complaints were related to the chest (100 [28.7 %]) and fever (99 [28.4 %]). ER imaging was positive in 207 visits (59.5 %), commonly revealing increased metastases (50 [14.4 %]), pneumonia (47 [13.5 %]), and other lung problems (12 [2.9 %]). Positive ER imaging was associated with inpatient admission (69.3 % [133/192] vs. 40.4 % [63/156], p&lt; 0.01). Multivariate survival analysis showed that positive ER imaging (hazard ratio [HR] = 2.35 [95% CI 1.44–3.83, p&lt; 0.01), admission (HR = 1.86 [95% CI 1.17–3.00], p&lt; 0.01), number of ER visits (HR = 3.08 [95% CI 1.62–5.83], p&lt; 0.01 for ≥ 3 visits) were associated with poorer survival. Conclusions: Imaging was able to delineate the cause for ER visits in children with cancer in over half of the cases. Positive ER imaging was associated with admission and worse survival.

Thalassemia is an inherited blood disorder characterized by defective hemoglobin production, ineffective erythropoiesis and chronic hemolytic anemia. Patients with both transfusion-dependent thalassemia (TDT) and non-transfusion dependent thalassemia (NTDT) have risk factors associated with severe SARS-CoV-2 infection including iron overload, endocrinopathies, massive splenomegaly or previous splenectomy and coagulopathy (Motta et al, Am J Hematol, 95: E198-E199., 2020). Although vaccination is encouraged for these patients, data on the efficacy and safety of anti Sars-CoV-2 vaccines are limited (Karimi, M, et al, Br J Haematol, 190: e137-e140, 2020; Mandana Zafari, et al, Hemoglobin, 45:1, 1-4, 2021) due to exclusion of these patients from clinical trials. In a single center, prospective, cohort study we compared 67 patients affected by TDT to 61 healthy controls (HC), matched for age and sex. Study population and HC received two doses of BNT162b2 anti-SARS-Cov-2 mRNA vaccine on days 1 and 21, between April 1st and May 15 th, 2021. Serological tests were performed by a commercially available immunoassay for the quantitative determination of anti-spike IgG antibodies to SARS-CoV-2. The results were reported as Arbitrary Units (AU)/mL, with a cut-off for defining response as 50 or greater AU/ml. Patients and HC samples were collected four weeks after the second dose of vaccine. Median age of patients was 43 years (range 19-77), 39% of them were male and 61% were female. Median age of HC was 39 years (range 19-86), 43% of them were male and 57% were female. All controls achieved a response (50 or greater AU/mL) to vaccination, whereas 66/67 (98,5%) patients responded. Antibody titers were significantly higher (p=0.0005) in the HC group (mean 9863 ± 7784; median 7712, range 1206-51664) compared to patients (mean 7945 ± 12326; median 4025, range 19-89202) (Figure 1). When analyzing the patients' factors, age, sex, transfusion interval, serum ferritin level, and spleen size did not impact on the response to vaccination. With a median follow-up of 12 weeks, no relevant side effects were recorded after vaccination and no case of COVID19 occurred among vaccinated TDT patients. In conclusion, BNT162b2 anti-SARS-Cov-2 mRNA vaccine demonstrated efficacy and safety in our cohort of TDT patients. Response rate was similar to that of HC. Nevertheless, antibody titers in TDT patients were significantly lower than in HC. Further observations are ongoing to assess duration of response, efficacy and possible factors influencing this finding.

Introduction

No relevant conflicts of interest to declare.

Milani: Celgene: Other: Travel support; Janssen-Cilag: Honoraria. Fazio: Janseen: Honoraria. Petrucci: GSK: Honoraria, Other: Advisory Board; Amgen: Honoraria, Other: Advisory Board; Takeda: Honoraria, Other: Advisory Board; BMS: Honoraria, Other: Advisory Board; Janssen-Cilag: Honoraria, Other: Advisory Board; Celgene: Honoraria, Other: Advisory Board; Karyopharm: Honoraria, Other: Advisory Board. Palladini: Pfizer: Honoraria; Siemens: Honoraria; Janssen Global Services: Honoraria, Other: advisory board fees. Nuvolone: Janssen-Cilag: Honoraria; Oncopeptides, Inc.: Research Funding.

Protozoa are important enteric pathogens in patients with human immunodeficiency virus (HIV) infection. In this study the prevalence of intestinal protozoa in 154 HIV-infected patients, with or without diarrhoea, in our region (Apulia, South Italy) was evaluated between December 1993 and February 1998. In the majority of patients CD4+ T cell count was below 200/μl. The overall prevalence of intestinal protozoa was 43/154 (27·92%). Twenty-eight (43·08%) out of 65 patients with diarrhoea and 15 (16·85%) out of 89 non-diarrhoeic patients were parasitized. In particular, in the group of 65 patients with diarrhoea the following protozoa were identified: Cryptosporidium parvum in 14 (21·54%), Blastocystis hominis in 7 (10·77%), microsporidia in 6 (9·23%), Giardia lamblia in 4 (6·15%) and Isospora belli in 1 (1·54%). Three patients were Cryptosporidium parvum-microsporidia co-infected. In patients without intestinal symptoms, prevalence was 3/89 (3·37%) for Cryptosporidium parvum, 9/89 (10·11%) for Blastocystis hominis, 1/89 (1·12%) for microsporidia and 2/89 (2·25%) for Giardia lamblia. A significant (P&lt;0·001) correlation was observed between protozoan infection and the presence of diarrhoea. In particular, Cryptosporidium parvum and microsporidia infections were significantly (P&lt;0·001) and P=0·046, respectively) associated with diarrhoeal illness. Moreover, the majority of cases of cryptosporidiosis were first diagnosed in the periods of heaviest rainfall. Therefore, drinking water contamination may be a possible source of human infection in our area.

The aim of our research is to check the SEM-EDS non-destructive analytical method for discriminating and locating the possible sources of obsidian artefacts. Moreover, in order to obtain a significant discrimination of Mediterranean obsidians, we analysed samples collected from outcrops of the major sources: Monte Arci (Sardinia) and Palmarola, Lipari, Pantelleria, Gyali and Melos islands. All samples were analysed by both XRF (whole rock) and SEM-EDS (glass and microliths-microphenocrysts). The XRF analysis reveals that major elements discriminate obsidian. The discrimination using major elements is very useful because the amount of trace elements is lower than the detection limit of a Si(Li) ED Detector. The major elements, particularly SiO2, Al2O3, CaO, Na2O and K2O, of obsidian glass discriminate the six main Mediterranean sources. Our work demonstrates, therefore, the possibility of discriminating different provenance of obsidian artefacts using SEM-EDS, by means of a relatively rapid, effective and above all non-destructive method.

This study was retrospectively performed in 574 short normal children and adolescents [328 underwent insulin tolerance test (ITT), 34 Clonidine test (CLON), 64 arginine test (ARG), 19 GHRH test, 52 ITT+CLON, 30 GHRH+CLON, and 47 ITT+CLON+GHRH) in order to evaluate the effect of pubertal stage on G H response to different tests and to identify the most likely mechanism of action of different stimuli. GH peak was higher during GHRH than in all other tests. Sex or start of pubertal development did not cause any GH peak difference. Low-responder (GH peak <10ng/ml) percentages were similar (ITT = 13.5%, CLON = 13.4%, ARG = 13.2%, GHRH = 10.6%) also when the subjects were divided according to sex and pubertal development. ITT+CLON showed discordant results in 42/99 subjects (30/42 = 71.4% were low-responders to ITT and 12/42 = 28.6% to CLON). GH peak appeared earlier during GHRH (85% <45 min) and later during CLON (78%: 60–120 min) than during all other tests; GH peak during ITT showed a wide variability of time. Negative correlations were found between GH peak during GHRH and chronological age, height and bone age and during CLON and chronological age. In conclusion our data show that these tests have similar GH secretagogue reliability.

The fractal dimensions of soil and peat humic acids equilibrated for various lengths of time in aqueous suspension at different pH values were determined by measuring their turbidity as a function of wavelength, with collaboration by scanning electron microscopy (SEM). Particle‐size distributions of the humic acid systems were also determined. The analysis of the power‐law dependence of the turbidity on the wavelength revealed that soil and peat humic acids may exhibit either a nonfractal or a mass fractal nature. Peat humic acid could also be described as a surface fractal. The passage from one regime to another depended on the pH and equilibration time. With an increase of either factor, the mass fractal dimension of humic acids decreased from about 2.8 to values close to 1.0. This trend, supported by SEM observations, suggested that humic particles in suspension evolve from compact, almost space‐filled structures with smooth surfaces, to less compact, fragmented and elongated structures with increasingly rough and irregular surfaces as the pH or time increases. Values of the mass fractal dimension close to 2.5 would reflect diffusion‐limited aggregation (DLA), whereas values close to 2.1 would suggest a reaction‐limited cluster‐cluster (RLA) aggregation model for humic acid. The fractal dimension thus represents a numerical parameter able to describe quantitatively the morphological features assumed by humic particles in suspension and to provide information on the underlying aggregation processes.

Electrocardiograms (heart rate, QRS voltage, QRS axis in the frontal plane, Q-Tc interval), echocardiograms [left ventricular fractional shortening (LVFS); preejection period (PEP); PEP/left ventricular ejection time (PEP/LVET) ratio; end-diastolic left ventricular free wall and interventricular septum thickness; presence of pericardial effusion], and thyrotropin (TSH), thyroxine (T4), and triiodothyronine (T3) serum levels were evaluated before and 1 week, 1 and 2 months after the start ofl-thyroxine (L-T4) therapy in 11 infants with congenital hypothyroidism (CH), aged 16–59 days when first seen.

To see whether or not reduced light input in children with congenital cataract produces degenerative myopia and whether it is associated with an impairment of the hypophyseal-adrenal cortical axis, the authors studied biometric values and circadian rhythm and cortisol reserve in nine children with monolateral and ten children with bilateral cataract.38.75% of patients had: (a) refractions <10D, (b) increased antero-posterior diameter of the eyeball, (c) varying degrees of myopic chorioretinitis, showing that the lack of light input induces degenerative myopia only in a group of patients who are probably genetically predisposed.The negative correlation between cortisol reserve and ocular lesions seems to reveal a precocious negative effect of the lack of light input on the development of the hypothalamic-hypophyseal-adrenal cortical axis. The alteration of the circadian cortisol rhythm and the reduction of the cortisol reserve found exclusively in children with monolateral cataract must be studied further to be explained.The slight increase in plasma cortisol levels earlier described in adults with acquired degenerative myopia was not found in children with congenital cataract. This difference could be due to: (a) special endocrine characteristics in children with congenital cataract, (b) endocrine differences between childhood and adulthood, (c) differing influences of hormonal factors on myopia, or vice versa, in childhood and adulthood.

Abstract. Thyroid function was investigated by a TRH test in 24 clinically prepubertal children, 3–15 years old with β-thalassaemia major; in 7 of them the test was repeated once and in 2 twice at intervals of at least 12 months. Basal T4, T3, TBG and TSH levels and the TSH levels during a TRH test were determined and correlated with age and serum ferritin levels.Basal serum T4, T3and TBG levels were lower and serum TSH levels were higher during the test and in the basal state in thalassaemia major children than in control children.These results show a compensated sub-clinical primary hypothyroidism.The transversal study did not show any significant correlation between the hormonal parameters studied and chronological age or serum ferritin levels.In contrast, the longitudinal study showed a significant correlation between pituitary-thyroidal axis function and siderosis (positive correlations between the variations of TSH levels as Δ, peak, 30 and 45 min values and the variations of serum ferritin levels).The thyroid impairment seems not to be correlated with serum ferritin levels in the transversal study because of the presence of an individual different sensitivity of the gland to the iron overload. The ferritin dependence of this impairment is shown only by longitudinal studies where individual differences in sensitivity of the gland are absent.Therefore iron chelation by desferrioxamine sc infusions, resulting in a decrease of ferritin, improves the deficient thyroid function.

Plasma growth hormone-releasing hormone (GHRH) was measured by radioimmunoassay in the cord blood from 32 healthy human newborns after 38–41 weeks of gestation. All were born by uncomplicated vaginal delivery. The GHRH levels in cord blood were 78.33 ± 8.35 pg/ml at 40 weeks of gestation, approximately threefold higher than the levels at 38 weeks of gestation (27.00 ± 2.55 pg/ml). No significant differences were found between girls and boys. The rise of plasma GHRH levels in cord blood of the full-term newborns between 38 and 40 weeks of gestation suggests a role of this peptide in the neonatal growth regulation.

Summary Corona textures between olivine and plagioclase or orthopyroxene and plagioclase are present in Hercynian gabbroic rocks from the Calabrian Sila Massif. They have been studied through optical and SEM investigations together with EDS and WDS analyses. Textural features indicate the existence of two extreme corona types formed during late magmatic stages or during subsolidus cooling. Magmatic coronas are characterized by an inner orthopyroxene layer and an outer orange-brown amphibole layer that might be in optical continuity with orthopyroxene and amphibole poikilites respectively. Subsolidus coronas consist of an inner layer of colourless amphibole and an outer layer of amphibole ± spinel. They sometimes form a collar also around plagioclase enclosed in olivine. A large spectrum in the composition of corona amphiboles from Ti-bearing pargasite to Mg-hornblende was observed. The variation in Ti content of amphibole was interpreted as a consequence of the different conditions of crystallization from late magmatic to subsolidus with temperatures ranging from 880°C to 580°C. The significant gahnite component in spinel possibly indicates that subsolidus reactions occurred in an open system. The pressure of formation constrained by the mineral assemblage of metamorphic basement rocks and by the neighbouring diorites has been estimated at 4 kbar.

ABSTRACTSince 2017, 10 vaccines are compulsory for newborns in Italy and unvaccinated children are not admitted to kindergartens. Recently the Italian Government announced the perspective of reforming the law about the compulsory vaccination. A debated started about the presence, in the same class of the schools, of unvaccinated and immunocompromised children. Cancer is the one of the most important cause of immunodepression among children: after the chemoterapy, there is a period of 13–23 months in which the cancer survivors have to come back at the school and at to the “normal life” (even for psychological exigency) but remain at risk of infectious disease for the immunodepression. The most important chance to protect this subgroup of patients remains the herd immunity.

Average growth hormone (GH) peaks following an i.v. growth hormone releasing hormone (GHRH) 1–29 stimulation test were significantly lower in 48 children and adolescents with GH deficiency (GHD) than in 20 age-matched controls (15.2+12.7 vs 37.5+28.1 ng/ml, 2P<0.001). Twelve patients exhibited a low GH peak (<5 ng/ml), 27 demonstrated a normal response (>10 ng/ml) and 9 showed an intermediate rise in plasma GH (5–10 ng/ml). Six of the 12 patients with low GH response to the first GHRH stimulation failed to respond to two other tests immediately before and after a 1 week priming with s.c. GHRH. These subjects with subnormal GH increase at repeat testing had total GHD (TGHD) and multiple pituitary hormone deficiency (MPHD) and had suffered from perinatal distress. On the contrary, 26 of 27 patients with normal GH response to the first test had isolated GHD and only a minority (8/27) had signs of perinatal distress. It is concluded that perinatal injuries primarily damage pituitary structures and that a pituitary defect more probably underlies more severe forms (TGHD and MPHD) of GHD.