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Counseling adolescent women with epilepsy (WWE) about reproductive health (contraception, sexual activity, and menstruation) is important given the teratogenicity of many antiseizure medications and high rates of contraception failure. Only a third of adolescent WWE report discussing contraception with their epileptologists, demonstrating a significant gap in counseling.We assessed factors associated with reproductive health counseling by pediatric neurologists via a retrospective chart review of adolescent (aged 12-18 years) WWE seen at a pediatric neurology clinic from 2018 to 2020.We analyzed 219 visits among 89 unique WWE. There were 23 documented discussions on contraception (11% of visits), 8 on sexual activity (4%), and 127 on menstruation (58%). When contraception was discussed, sexual activity and menstruation were more frequently discussed. Female providers were more likely to document a discussion of menstruation (OR = 3.2, 95% CI = [1.6, 6.4]). WWE who were older at the time of visit or who had their first seizure at an older age were more likely to have documented discussions of contraception and sexual activity. Neither details of treatment regimen nor epilepsy type was associated with documentation of counseling.A minority of adolescent WWE have documented reproductive health discussions, demonstrating a need for quality improvement projects to address this gap in care.

This work was carried out within the context of an R&D project on morphable polymer matrix composites (PMC), actuated by shape memory alloys (SMA), to be used for active aerodynamic systems in automotives. Critical issues for SMA–polymer integration are analyzed that are mostly related to the limited strength of metal–polymer interfaces. To this aim, materials with suitable thermo-mechanical properties were first selected to avoid premature activation of SMA elements during polymer setting as well as to avoid polymer damage during thermal activation of SMAs. Nonstandard samples were manufactured for both static and fatigue pullout tests under thermo-mechanical loading, which are made of SMA wires embedded in cylindrical resin blocks. Fully coupled thermo-mechanical simulations, including a special constitutive model for SMAs, were also carried out to analyze the stress and temperature distribution in the SMA–polymer samples as obtained from the application of both mechanical loads and thermal activation of the SMA wires. The results highlighted the severe effects of SMA thermal activation on adhesion strength due to the large recovery forces and to the temperature increase at the metal–polymer interface. Samples exhibit a nominal pullout stress of around 940 MPa under static mechanical load, and a marked reduction to 280 MPa was captured under simultaneous application of thermal and mechanical loads. Furthermore, fatigue run-out of 5000 cycles was achieved, under the combination of thermal activation and mechanical loads, at a nominal stress of around 200 MPa. These results represent the main design limitations of SMA/PMC systems in terms of maximum allowable stresses during both static and cyclic actuation.

Objectives: To describe the spectrum of pediatric inflammatory neurologic diseases and compare the sensitivity of ancillary testing for these diagnoses. Methods: We analyzed clinical features and outcomes of 98 children with an immune-mediated central nervous system disorder. We compared sensitivities of each diagnostic modality. Results: We identified the following diagnoses: acute cerebellar ataxia (n = 14; 14.3%), acute demyelinating encephalomyelitis (n = 13; 13.3%), multiple sclerosis (MS) (n = 18; 18.4%), anti- N-methyl-d-aspartate receptor encephalitis (anti-NMDAR encephalitis) (n = 15; 15.3%), encephalitis not otherwise specified (n = 12; 12.2%), and “Other” (n = 26; 26.5%). “Other” included acute transverse myelitis, neuromyelitis optica, central nervous system lupus, primary central nervous system vasculitis, Rasmussen encephalitis, opsoclonus myoclonus ataxia syndrome, and clinically isolated syndrome. The mean age of onset of all diagnoses was 7.9 ± 5.5 years. The diagnostic sensitivity of magnetic resonance imaging (MRI) for acute demyelinating encephalomyelitis and multiple sclerosis was 92.3% and 94.4%, respectively. Cerebrospinal fluid was sensitive for multiple sclerosis in 92.3%, where 75% of patients had cerebrospinal fluid oligoclonal bands. Electroencephalogram (EEG) coupled with cerebrospinal fluid studies was highly sensitive for anti-NMDAR encephalitis (100%). EEG was sensitive for acute demyelinating encephalomyelitis and encephalitis not otherwise specified (77.8% and 80%). No diagnostic studies were sensitive for acute cerebellar ataxia. Seventy-three percent of patients with multiple sclerosis had residual deficits. Thirty-six percent of anti-NMDAR encephalitis patients were nonverbal and wheel-chair bound. Conclusions: We found that MRI is useful for detecting multiple sclerosis and acute demyelinating encephalomyelitis, cerebrospinal fluid is helpful in diagnosing multiple sclerosis and anti-NMDAR encephalitis, and EEG is often abnormal in suspected anti-NMDAR encephalitis, acute demyelinating encephalomyelitis, and encephalitis not otherwise specified. Neurologic outcome at follow-up was unfavorable in patients with multiple sclerosis and anti-NMDAR encephalitis.

Highlights • ReDoV infection may not be systemic or the presence of circulating virus can be only intermittent. • ReDoV infection is mainly present in the respiratory tract., Background Redondovirus (ReDoV) is a recently discovered circular, Rep-encoding single-stranded DNA (CRESS-DNA) virus in humans. Its pathogenesis and clinical associations are still completely unknown. Methods The presence of ReDoV DNA was investigated in biological specimens of 543 Italian subjects by in-house developed PCR assays. Results The overall ReDoV prevalence was about 4% (23 of 543 samples). The virus was detected in 22 of 209 (11 %) respiratory samples. One stool sample was also ReDoV positive. Viral DNA was not found in blood samples from immunocompetent and immunosuppressed subjects and cerebrospinal fluids from patients with neurological diseases. Genomic nucleotide differences were detected among the ReDoV isolates by sequencing a 582-nucleotide fragment of the capsid gene of the viral genome. Conclusions The results demonstrate that ReDoV is mainly present in the respiratory tract of infected people. Further investigations are needed to reveal possible clinical implications of this new CRESS-DNA virus in humans.

Neurologic infections during pregnancy represent a significant cause of maternal and fetal morbidity and mortality. Immunologic alterations during pregnancy increase the susceptibility of the premature brain to damage. This chapter summarizes the epidemiology, pathophysiology, and clinical manifestations in the pregnant woman and the infant, and the diagnosis, treatment, and prevention of the major viral, parasitic, and bacterial infections known to affect pregnancy. These organisms include herpes virus, parvovirus, cytomegalovirus, varicella, rubella, Zika virus, toxoplasmosis, malaria, group B streptococcus, listeriosis, syphilis, and tuberculosis. There is an emphasis on the important differences in diagnosis, treatment, and fetal outcome between trimesters. An additional overview is provided on the spectrum of neurologic sequelae of an affected infant, which ranges from developmental delay to hydrocephalus and seizures.

The possible cooperation between hypnotizability-related and placebo mechanisms in pain modulation has not been consistently assessed. Here, we investigate possible genetic bases for such cooperation. The OPRM1 gene, which encodes the μ1 opioid receptor-the primary site of action for endogenous and exogenous opioids-is polymorphic in the general population for the missense mutation Asn40Asp (A118G, rs1799971). The minor allele 118G results in decreased levels of OPRM1 mRNA and protein. As a consequence, G carriers are less responsive to opioids. The aim of the study was to investigate whether hypnotizability is associated with the presence of the OPRM1 polymorphism. Forty-three high and 60 low hypnotizable individuals, as well as 162 controls, were genotyped for the A118G polymorphism of OPRM1. The frequency of the G allele was significantly higher in highs compared to both lows and controls. Findings suggest that an inefficient opioid system may be a distinctive characteristic of highs and that hypnotic assessment may predict lower responsiveness to opioids.

Background Opioid overprescribing is a major contributor to the opioid crisis. The lack of procedure-specific guidelines contributes to the vast differences in prescribing practices. Objective Create opioid-prescribing consensus guidelines for common dermatologic procedures. Methods We utilized a four-step modified Delphi method to conduct a systematic discussion among a panel of providers in the fields of general dermatology, dermatologic surgery, and cosmetics/phlebology to develop opioid-prescribing guidelines for some of the most common dermatologic procedural scenarios. Guidelines were developed for opioid-naive patients undergoing routine procedures. Opioid tablets were defined as oxycodone 5-mg oral equivalents. Results Postoperative pain after most uncomplicated procedures (76%) can be adequately managed with acetaminophen and/or ibuprofen. Group consensus identified no specific dermatological scenario that routinely requires more than 15 oxycodone 5-mg oral equivalents to manage postoperative pain. Group consensus found that 23 percent of the procedural scenarios routinely require 1-10 opioid tablets, while only one routinely requires 1-15 opioid tablets. Limitations These recommendations are based on expert consensus in lieu of quality evidence-based outcomes research. These recommendations must be individualized to accommodate patients’ comorbidities. Conclusions Procedure-specific opioid-prescribing guidelines may serve as a foundation to produce effective and responsible postoperative pain management strategies after dermatologic interventions.

Two adjacent nucleotide substitutions in exon 2 characterize the novel class II HLA-DPB1*687:01 allele.

Background aims Mesenchymal stromal cells (MSCs) modulate the immune response and represent a potential treatment for inflammatory and autoimmune diseases. We hypothesized that this feature could be potentiated by co-administering anti-inflammatory cytokines. In this article, we asked whether engineering of Wharton Jelly–derived human MSCs (WJ-hMSCs) to express an anti-inflammatory cytokine increases cell immunomodulatory properties without altering their native features. Methods We used Epstein-Barr virus–derived interleukin-10 (vIL-10), which shares some immunosuppressive properties with human IL-10 but lacks immunostimulatory activity. Engineering was accomplished by transducing WJ-hMSCs with a self-inactivating feline immunodeficiency virus–derived vector co-expressing vIL-10 and herpes simplex virus type-1 thymidine kinase (TK). TK was added to allow future tracking of WJ-hMSC in vivo by positron electron tomography (PET). Results The results show that (i) expression of TK and/or vIL-10 does not change WJ-hMSC phenotypic and functional properties; (ii) vIL-10 is secreted, biologically active and enhances the immunosuppressing functions of WJ-hMSCs; (iii) v-IL10 and TK can be produced simultaneously by the same cells and do not interfere with each other. Discussion WJ-hMSCs engineered to secrete vIL-10 could be a powerful tool for adoptive cell therapy of immune-mediated diseases, and therefore, additional studies are warranted to confirm their efficacy in suitable animal disease models.

A novel HLA-DPB1 allele, named HLA-DPB1*647:01, identified in a leukemia patient.

Laser fabrication techniques offer great advantages for fabrication of materials suitable for biomedical applications since they allow flexible, contactless, material independent, high precision processes. A multi-technique space resolved and surface sensitive approach is advised to fully characterize the properties of laser processed materials.

Since the 1960s the Holzworth method has remained a primary tool for operational mixed-layer height determination. The air volume through which ground-based pollutants vertically disperse defines the mixed layer. The appeal of this method rests on the simple mechanics of making a forecast where knowledge of the surface air temperature in concert with the background vertical structure is sufficient. The National Weather Service routinely issues forecasts using this method for air-quality and wildland fire activities. Methods of this type that are based principally on the static stability structure of the atmosphere and exclude vapor content or dynamical processes (e.g., advection and wind shear) can misrepresent the mixing height calculation. Systematic errors, such as the height being too low or high, can complicate wildland fire activities (e.g., go/no-go burn decisions). Motivation for the present study emerges from this premise, and thus examines the mixing height computed from four methods. Mixing height methods employed in this study include Holzworth, Stull, bulk Richardson number, and turbulent kinetic energy—where the latter two include dynamical processes. Mixing height also was derived from satellite-based lidar data to provide an observed proxy and validation. Results from a method intercomparison show that turbulent kinetic energy is the most robust and well suited as a national standard method for operational use—having both thermodynamic and dynamic processes incorporated. The bulk Richardson number and Stull methods are other possibilities because their calculations are not model dependent and heights are consistent with those from turbulent kinetic energy.

The synthesis of iron oxide nanoparticles (FexOy NPs) is an important area of research because of the growing scientific and technological interest for their potential applications. Between iron oxide nanomaterials, magnetite (Fe3O4) and maghemite (?-Fe2O3) are especially promising for applications in nanomedicine and tissue engineering due to their biocompatibility and low toxicity when in contact with the human tissues. Laser Ablation in Liquid (LAL) is one of the simplest, cheapest and cleanest method for the synthesis of FexOy NPs, since it does not require chemical precursors and nanoparticles are directly obtained in water as a stable colloidal solutions. We have produced FexOy NPs by LAL technique in water, using a Ti:sapphire laser source (? = 800 nm, ? = 100 fs, repetition rate = 1 kHz). The obtained FexOy NPs have been mixed with hydroxyapatite (HA) powder and then the pressed powder has been used for the deposition of composite HA& FexOy thin films by Pulsed Laser Deposition (laser source: Nd:YAG, ? = 532 nm, ? = 10 ns, repetition rate = 10 Hz). During the nanosecond ablation process complete oxidation of the iron nanoparticles has been observed. The characteristics of the produced nanoparticles and films deposited at different substrate temperature have been investigated by microscopic (TEM and SEM) and spectroscopic (FT-IR and ?-Raman) techniques. Magnetic behavior of iron FexOy NPs and deposited films has been studied. Considering that nanostructured film coating can improve the bioactivity of the implant and that the presence of FexOy NP benefits cells growth, we can expect that successful implant could be obtained.

The novel HLA-C*04:288 differs from HLA-C*04:01:01:06 by a single nucleotide substitution in exon 2.

The HLA-B*18:122 allele showed four nucleotide differences from HLA-B*18:01:01:01.

One nucleotide substitution at residue 142 of the HLA-DRB1*13:01:01 results in a new allele, HLA-DRB1*13:215.

A polysaccharide-flavonoid conjugate was developend and proposed for the treatment of pancreatic ductal adenocarcinoma (PDAC).The conjugate was synthesized by free radical grafting reaction between catechin and dextran. The chemical characterization of the conjugate was obtained by UV-Vis, 1H-NMR, FT-IR and GPC analyses, while the functionalization degree was determined by the Folin-Ciocalteu assay. The biological activity of the catechin-dextran conjugate was tested on two different cell lines derived from human pancreatic cancer (MIA PaCa-2 and PL45 cells), and the toxicity towards human pancreatic nestin-expressing cells evaluated.Both the cancer cell lines are killed when exposed to the conjugate, and undergo apoptosis after the incubation with catechin-dextran which resulted more effective in killing pancreatic tumor cells compared to the catechin alone. Moreover, our experimental data indicate that the conjugate was less cytotoxic to human pancreatic nestin-expressing cells which are considered a good model of non-neoplastic pancreatic cells.The suitability of newly synthesized Dextran-Catechin conjugate in the treatment of PDAC was proved confirming the high potential application of the proposed macromolecula system in the cancer therapy.

Two novel alleles, HLA-A*31:125 and HLA-B*44:269, are described in Italian bone marrow donors.

The axiom of human leukocyte incompatibility (HLA) incompatibility has always led scientists to consider cancer transmission between HLA-different individuals impossible. In fact, cancer transmission between individuals represents a frightening possibility in animal populations with limited HLA diversity or for rare cancers exploiting downregulation of HLA expression. We review here evidence from nonhuman models and settings for interhuman transmission.

Hypnotizability is associated with a few physiological characteristics also in the normal awake state. Differences in flow-mediated dilation (FMD) have been observed in subjects with high (Highs) or low (Lows) hypnotizability during nociceptive stimulation. FMD is largely due to the nitric oxide (NO) produced by vascular endothelium through the activity of NO synthase (eNOS). Endothelial NOS is encoded by the NOS3 locus. Aim of this pilot study was to investigate the association between genetic polymorphisms of NOS3 involved in NO blood levels and hypnotizability. Nine single nucleotide polymorphisms (SNPs) of the NOS3 gene were analyzed in the DNA of 24 Highs, 22 Lows, and 61 newborns. Two SNPs, rs1800783 (-1474 T/A) and rs2070744 (-786 T/C), located in the upstream and promoter region of the gene, respectively, showed significant differences between Highs and Lows in allele frequency. Haplotype analysis showed that the newborns were in linkage equilibrium for these SNPs, whereas both Highs and Lows showed linkage disequilibrium. The A-C haplotype (associated with lower NO availability in the general population) was more frequent in Highs, and the T-T haplotype was more frequent in Lows. Thus, the lower FMD reduction observed in Highs during nociceptive stimulation, which is indicative of higher NO availability, should be due to greater efficacy of shear stress-related transcriptional factors and/or to lower effects of NOS inhibitory controls. A consequent theoretical proposal concerns the possible role of NO in the brain vessels where, in stimulation conditions, NO diffusion to the extracellular compartment might be involved in hypnotic responding.

Objective: Two missense mutations of the HFE gene, one (C282Y) being a major gene for hereditary hemochromatosis and the other (H63D) playing a minor role in this disease, are carried by different haplotypes. Among other sequence variants of HFE, IVS2+4t/c polymorphism has been reported as a possible splicing mutation or risk modifier. Our aims were to identify sequence variants possibly associated with iron overload in our population, to study the intragenic haplotypes of the HFE gene, and to evaluate the role of IVS2+4t/c in hyperferritinemia. Methods: We screened by direct sequencing the coding sequence and intron–exon boundaries of HFE in 265 patients with hyperferritinemia and 185 subjects from the general population. Results: Linkage disequilibrium between the three pairs of polymorphic sites was complete between H63D and C282Y, whereas all four gametic types were present for both the H63D–IVS2+4t/c and the IVS2+4t/c–C282Y site pairs. The data supported a model in which the IVS2+4t/c polymorphism was ancestral, the D63 mutation occurred on the t chromosome, and the Y282 mutation occurred on the c chromosome; after the population spread of both mutations, intragenic recombination occurred on both sides of the t/c polymorphism, generating the rare haplotypes D63-cIVS2+4-C282 and H63-tIVS2+4-Y282. Conclusions: The IVS2+4c/t is a neutral polymorphism with regard to risk of iron overload. The presence of recombinant haplotypes on both its sides suggests a considerable evolutionary age of the two main risk alleles.

Abdominal aortic aneurysm (AAA) has a multifactorial aetiology and the importance of genetic components is getting increasing interest. Alteration in the structure of the vascular extracellular matrix has been described in AAA. Matrix metalloproteinases (MMPs) degrade extracellular matrix proteins which alter the vessel wall stability. We evaluated two different polymorphisms, a CA repeat and a cytosine to thymidine transition in the promoter sequence of MMP-9 gene for frequency in 146 patients with AAA. We compared the results with those of 156 healthy subjects. No difference was found in the allelic distribution of either polymorphisms. We therefore found no evidence that MMP-9 is a marker of susceptibility for AAA.

A novel class I human leukocyte antigen allele HLA-A*24:309 is described.

Binary Mg-Ca alloys, with a low Ca content (0.6 - 3 wt.%) have demonstrated to be very promising for orthopedic applications [1]. The main problem is that these alloys exhibit fast degradation when inserted in bones. The best way to minimize corrosion processes seems the coating of the alloy surface by biocompatible materials, which could also improve the biocompatibility of Mg-Ca surface [2]. Among the different materials which can be used as biocompatible coatings, bioactive glasses are very promising since, compared to synthetic hydroxyapatite, the surface layer in this case is more similar, in terms of crystallinity, to the apatite of bone tissue [3]. In this paper we have used RKKP glass ceramic (SiO2 - 43.68, ?-Ca3(PO4)2 - 24.00, CaO - 18.40, CaF2 - 4.92, Na2O - 4.53, MgO - 2.78, K2O - 0.19, Ta2O5 - 1.00, La2O3 - 0.50, all in wt%) as coating material for a Mg-Ca substrate. The technique used to deposit the coatings was Pulsed Laser Deposition (PLD). In fact, PLD have already successfully used to deposit films of a large number of materials with technological interest [4]. In particular, RKKP glass ceramic films, deposited by PLD on titanium substrates, have shown a composition reflecting very well that of the ablation target [5]. The deposition experiments have been performed in high vacuum by a frequency doubled Nd:YAG laser (? = 532 nm, ? = 7 ns, repetition rate = 10 Hz). The deposited films have been characterized using different techniques like Scanning Electron Microscopy, Atomic Force Microscopy, Fourier Transform Infrared Spectroscopy, Angular and Energy Dispersive X-ray Diffraction, in order to characterize the coatings from chemical composition, structural and morphological point of view. The obtained results confirm us the potential of bioactive glass coatings for Mg-Ca alloys, due to a good homogeneity of the coatings, good adhesion to the substrate and a reduced rate of hydrogen release in simulated medium. Future studies will be performed in order to observe the influence of the coatings on biodegradation and biocompatibility properties.

HLA-B*18:108 has two nucleotide changes from B*18:01:01:02 at nt 430 where A -> G and nt 431 where G -> A.

Background About a third of patients with acute stroke and no prior diagnosis of diabetes have hyperglycaemia during the acute phase of stroke. Whether this is an acute stress response or a reflection of underlying diabetes is controversial. Aim To assess whether impaired glucose metabolism in patients with acute ischaemic stroke and no previous diagnosis of diabetes persists after 3 months, and whether such persistence can be predicted. Design Prospective observational study. Methods We enrolled 106 patients with acute ischaemic stroke and no history of diabetes. Fasting blood glucose, serum insulin and the insulin resistance index HOMA were recorded during hospital stay. A standard oral glucose tolerance test was performed at discharge and 3 months later. Results Ten patients did not complete the study. Eighty-one patients (84.4%) had abnormal glucose metabolism at discharge and 62 (64.6%) after 3 months. Thirty-seven (38.5%) had impaired glucose tolerance at discharge and 26 (27.1%) after 3 months. Forty-four (45.8%) had diabetes at discharge, and 36 (37.5%) at 3 months. Post-load hyperglycaemia at discharge was a predictor of diabetes after 3 months. A plasma glucose cut-off of 11.7 mmol/l (210 mg/dl) had a specificity of 90.0% and a positive predictive value of 81.3%. HOMA increased progressively from patients with normal glucose metabolism to those with newly diagnosed diabetes. Discussion Impaired glucose tolerance and previously unrecognized diabetes could be detected early in the stroke course, and persisted after 3 months in more than two-thirds of our patients. Post-load hyperglycaemia during the acute phase of stroke may be useful in identifying patients with abnormal glucose metabolism, which places them at risk for adverse outcomes, including cardiovascular disease.

The placenta acts as an immunological barrier between the mother and the fetal "graft", allowing two antigenically different organisms to tolerate one another. In placentae from preeclamptic women, we have demonstrated, by an ultrastructural assessment and an immunohistochemical study, a placental barrier breakage leading to the mixing of maternal and fetal antigenically different blood. This condition could be responsible for the triggering of a maternal rejection reaction that we presume to be at the basis of the preeclamptic syndrome. Thus, we have investigated the Human Leukocyte class II DR antigens (HLA-DR), whose role in self and non-self recognition is well known, in women with preeclampsia, their partners and in control couples using the serological Terasaki tecnique. The results showed a statistically significant increase of HLA-DR homozygosity and a reduced antigenic variety in the preeclamptic women and their partners with respect to controls. In this update, we have examined the 2nd exon of the human gene, HLA-DRB1, on the short arm of the chromosome 6 using DNA sequence-based typing (S-BT) PCR in 56 preeclamptic couples and 64 control couples. The results have confirmed the significant excess of HLA-DR homozygosity in couples associated with preeclampsia versus controls. From our results, it emerges that HLA-DR homozygosity and the reduced antigenic variety seem to be associated to a major risk for preeclampsia, which further appears to be a "couple's disease".

Background: Recently it has been suggested that microchimerism may have a significant role in the aetiopathogenesis of some autoimmune diseases. Objectives: To evaluate the incidence of microchimerism in systemic lupus erythematosus (SLE), to quantify the phenomenon, to evaluate changes of microchimerism during follow up, and to correlate these data with clinical and laboratory variables. Methods: Patients were selected for the study on the basis of the following criteria: ( a ) pregnancy with at least one male offspring; ( b ) no history of abortion and blood transfusion. Microchimerism was detected using a competitive nested polymerase chain reaction for a specific Y chromosome sequence and an internal competitor designed ad hoc. Disease activity and organ involvement were also evaluated. Results: Sixty samples from 22 patients with SLE and 24 healthy controls were examined. Microchimerism was seen in 11 (50%) patients and 12 (50%) controls. The mean number of male equivalent cells was 2.4 cells/100 000 (range 0.1–17) in patients with SLE and 2.5 (range 0.2–1.8) in healthy controls. No differences in the incidence of microchimerism or in the number of microchimeric cells were found between patients and healthy controls. Patients with a history of lupus nephritis had a higher mean number of fetal cells than patients with no such history. Disease activity did not appear to correlate with microchimerism. Conclusions: The preliminary data suggest that microchimerism does not interfere with the disease course of SLE, although further analysis on larger groups will be necessary to confirm these observations.

Biogenic amines (BAs) are basic compounds of low molecular weight derived internally from plants, fruits, and vegetables. These organic bases can be divided into several groups according to their chemical structure—aromatic (tyramine and phenylethylamine), aliphatic (putrescine and cadaverine), or heterocyclic (histamine and tryptamine)—or in relation to the number of amino groups into monoamines (phenylethylamine and tyramine) and diamines (histamine, cadaverine, and putrescine). They can also be classified as volatile (phenylethylamine) and nonvolatile (histamine, cadaverine, putrescine, spermine, agmatine, tryptamine, and tyramine) BAs (EFSA, 2011). Figure 4.1 shows the chemical structures of the most important amines. BAs execute a number of crucial functions in the physiology and development of eukaryotic cells. The most active BAs are histamine and tyramine. Polyamines such as putrescine, spermine, and spermidine also play essential roles in cell growth and differentiation via the regulation of gene expression and the CONTENTS

Background Angelman syndrome (AS) is a neurological disorder caused by genetic defects of the chromosome region 15q11-q13; some 70–80% of cases are due to deletions of the maternal allele, as the paternal copy is imprinted. Design and methods A maternal deletion at D15S986 was reported in a suspected case of AS; this marker is located in intron 2 of the ATP10C gene, which has been implicated in the development of AS. A segment of ~ 830 bp, including this marker and the primers used in routine genetic test, was cloned and sequenced. Results A single nucleotide deletion (named ATP10C*c.760+3808delA, GenBank accession number HQ856823 ) was detected in the middle of the forward primer, leading to allele dropout. A large European population sample (N = 363) was typed, and the detected variant was characterized as a novel polymorphism, with allele frequencies of 0.882 (TAT allele) and 0.118 (T-T allele). Conclusions An alternative primer set was developed, for which the segregation pattern of D15S986 in the proband extended family was normal. It can replace the currently used set.

A novel HLA-DPB1 allele, named DPB1*296:01, was identified in the Thai mother of a hematologic patient.

Summary A novel HLA-A allele, HLA-A*68:105, was detected by sequence-based typing (SBT) in an Italian bone marrow donor. It differs from HLA-A*68:01:02 at five nucleotides, three intronic, nt 699 T->G (intron 2), nt 705 T->C (intron 2) and nt 2770 G->A (intron 7), and two located in exon 3, at positions 726 A-G (codon 94 Ile->Val) and 733 T-G (codon 97 Arg->Met), respectively.

Graft vascularization is a crucial step to obtain stable normoglycemia in pancreatic islet transplantation. Endothelial progenitor cells (EPCs) contribute to neoangiogenesis and to the revascularization process during ischaemic events and play a key role in the response to pancreatic islet injury. In this work we co-transplanted EPCs and islets in the portal vein of chemically-induced diabetic rats to restore islet vascularization and to improve graft survival. Syngenic islets were transplanted, either alone or with EPCs derived from green fluorescent protein (GFP) transgenic rats, into the portal vein of streptozotocin-induced diabetic rats. Blood glucose levels were monitored and intraperitoneal glucose tolerance tests were performed. Real time-PCR was carried out to evaluate the gene expression of angiogenic factors. Diabetic-induced rats showed long-lasting (6 months) normoglycemia upon co-transplantation of syngenic islets and EPCs. After 3–5 days from transplantation, hyperglycaemic levels dropped to normal values and lasted unmodified as long as they were checked. Further, glucose tolerance tests revealed the animals' ability to produce insulin on-demand as indexed by a prompt response in blood glucose clearance. Graft neovascularization was evaluated by immunohistochemistry: for the first time the measure of endothelial thickness revealed a donor-EPC-related neovascularization supporting viable islets up to six months after transplant. Our results highlight the importance of a newly formed viable vascular network together with pancreatic islets to provide de novo adequate supply in order to obtain enduring normoglycemia and prevent diabetes-related long-term health hazards.

A newly identified allele, named HLA B*15:276, differs from B*15:01:01:01 by the single nucleotide substitution 511T-C at codon 147 (Trp → Arg) in exon 3.

Higher brain dopamine content depending on lower activity of Catechol-O-Methyltransferase (COMT) in subjects with high hypnotisability scores (highs) has been considered responsible for their attentional characteristics. However, the results of the previous genetic studies on association between hypnotisability and the Catechol-O-Methyltransferase (COMT) single nucleotide polymorphism (SNP) rs4680 (Val158Met) were inconsistent. Here, we used a selective genotyping approach to re-evaluate the association between hypnotisability and COMT in the context of a two-SNP haplotype analysis, considering not only the Val158Met polymorphism, but also the closely located rs4818 SNP. An Italian sample of 53 highs, 49 low hypnotizable subjects (lows) and 57 controls, were genotyped for a segment of 805 bp of the COMT gene, including Val158Met and the closely located rs4818 SNP. Our selective genotyping approach had 97.1% power to detect the previously reported strongest association at the significance level of 5%. We found no evidence of association at the SNP, haplotype and diplotype levels. Thus, our results challenge the dopamine-based theory of hypnosis and indirectly support recent neuropsychological and neurophysiological findings reporting the lack of any association between hypnotisability and focused attention abilities.

HLA-B*18:108 has two nucleotide changes from B*18:01:01:02 at nt 430 where A → G and nt 431 where G → A.

MLL is fused to ENL or ELL in acute leukemias that contain t(ll;19)(q23;p13). Although ENL and ELL localize to chromosome 19, bands p13.3 and p13.1, respectively, these breakpoints are not always readily distinguished by standard cytogenetics. We therefore used reverse transcriptase-polymerase chain reaction (RT-PCR) assays to analyze 26 cases of childhood acute leukemia containing t(11;19) to determine the frequencies of ENL and ELL involvement. All 17 cases of acute lymphoblastic leukemia (ALL) had MLL/ENL fusion transcripts. By contrast, of the 9 cases of acute myeloid leukemia (AML) analyzed, 6 had MLL/ENL fusions, 2 had MLL/ELL fusions, and 1 case had no RT-PCR- detectable MLL fusion mRNA. These data suggest that the majority of 11;19 translocations involve ENL, whereas involvement of ELL is relatively uncommon in childhood acute leukemia and may be restricted to AML.

One nucleotide substitution at residue 142 of the HLA-DRB1*13:01:01 results in a new allele, HLA-DRB1*13:215.

The t(2;5)(p23;q35) translocation was initially identified in cases of anaplastic large-cell lymphoma (ALCL) that expressed the Ki-1 (CD30) antigen. We have recently cloned this translocation and shown it to encode a chimeric product consisting of the N-terminal portion of a nonribosomal nucleolar phosphoprotein, nucleophosmin (NPM), from chromosome 5, fused to the kinase domain of a novel transmembrane tyrosine-specific protein kinase, anaplastic lymphoma kinase (ALK), from chromosome 2. To better define the spectrum of lymphomas that contain this translocation, we have analyzed 70 cases of non-Hodgkin's lymphoma (NHL) for expression of the t(2;5)-derived NPM/ALK chimeric message by reverse transcriptase-polymerase chain reaction (RT-PCR). Using a previously described set of oligonucleotide primers, NPM/ALK chimeric transcripts were detected in 21 of 22 cases that contained the t(2;5) by cytogenetic analysis and in 10 of 48 cases that either lacked evidence of the t(2;5) or had unsuccessful cytogenetics. In all but 1 case, the NPM/ALK PCR products were of identical size and sequence, suggesting that the genomic chromosome breaks are clustered in a single intron in both NPM and ALK. The NPM/ALK-expressing cases were not confined to NHLs with anaplastic morphology and included 15 ALCLs, 6 immunoblastic lymphomas, and 10 diffuse large-cell lymphomas. Moreover, only slightly greater than half of the cases with anaplastic morphology and 59% of CD30-expressing cases were NPM/ALK positive. Thus, neither anaplastic morphology nor the expression of CD30 accurately predicted the presence of this molecular genetic subtype of lymphoma.

The tandemly linked p16INK4aMTS1 and p15INK4b/MTS2 genes on chromosome 9, band p21 encode proteins that function as specific inhibitors of the cyclin D-dependent kinases CDK4 and CDK6. This locus undergoes frequent bi-allelic deletion in human cancer cell lines, suggesting that the encoded proteins may function as tumor suppressors. However, more recent analysis of primary tumor samples has shown a much lower frequency of abnormalities affecting this region, raising doubt over the importance of these proteins in human malignancies. Hemizygous deletions and rearrangements of chromosome 9, band p21, are among the most frequent cytogenetic abnormalities detected in pediatric acute lymphoblastic leukemia (ALL), occurring in approximately 10% of cases. To determine if the p16INK4a/p15INK4b locus might be the target of these chromosomal lesions, we analyzed both genes in primary clinical samples from 43 pediatric ALL patients using interphase fluorescence in situ hybridization, Southern blot analysis, and the polymerase chain reaction. Deletions of p16INK4a/p15INK4b were identified in 18 of 20 cases with cytogenetically observed abnormalities of 9p and 5 of 23 with apparently normal chromosomes 9p, with the majority containing bi-allelic deletions (16 homozygous/7 hemizygous). Although most homozygous deletions involved both genes, Southern blot analysis showed an interstitial deletion in a single case that was confined to p16INK4a, suggesting that p15INK4b was not the critical target gene in this case. Sequence analysis of both p16INK4a and p15INK4b in all seven cases with hemizygous deletions failed to show mutations within the coding regions of the retained alleles. In this select group of patients, deletion of p16INK4a/p15INK4b was associated with T-cell phenotype, nonhyperdiploid karyotype (< 50 chromosomes), and poor event-free survival. These findings indicate that deletion of the p16INK4a/p15INK4b locus is one of the most common genetic abnormalities so far detected in pediatric ALL, and that loss of one or more of these cell cycle kinase inhibitors is important in leukemogenesis.

A novel HLA-B*51:01:29 allele differs from B*51:01:01 at one nucleotidic position in the exon 3.