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Heterodyne detection based on interband cascade lasers (ICL) has been demonstrated in a wide range of different applications. However, it is still often limited to bulky tabletop systems using individual components such as dual laser setups, beam shaping elements, and discrete detectors. In this work, a versatile integrated ICL platform is investigated for tackling this issue. A RF-optimized, two-section ICL approach is employed, consisting of a short section typically used for efficient modulation of the cavity field and a long gain section. Such a laser is operated in reversed mode, with the entire Fabry–Pérot waveguide utilized as a semiconductor optical amplifier (SOA) and the electrically separated short section as detector. Furthermore, a racetrack cavity is introduced as on-chip single-mode reference generator. The field of the racetrack cavity is coupled into the SOA waveguide via an 800 nm gap. By external injection of a single mode ICL operating at the appropriate wavelength, a heterodyne beating between the on-chip reference and the injected signal can be observed on the integrated detector section of the SOA-detector.

Dual-comb (DC) ranging is an established method for high-precision and high-accuracy distance measurements. It is, however, restricted by an inherent length ambiguity and the requirement for complex control loops for comb stabilization. Here, we present a simple approach for expanding the ambiguity-free measurement length of DC ranging by exploiting the intrinsic intensity modulation of a single-cavity dual-color DC for simultaneous time-of-flight and DC distance measurements. This measurement approach enables the measurement of distances up to several hundred kilometers with the precision and accuracy of a DC interferometric setup while providing a high data acquisition rate (≈2kHz) and requiring only the repetition rate of one of the combs to be stabilized.

The discovery of circulating fetal DNA in the plasma of pregnant women has greatly promoted advances in noninvasive prenatal testing. Screening performance is enhanced with higher fetal fraction and analysis of samples whose fetal DNA fraction is lower than 4% are unreliable. Although current approaches to fetal fraction measurement are accurate, most of them are expensive and time consuming. Here we present a simple and cost-effective solution that provides a quick and reasonably accurate fetal fraction by directly evaluating the size distribution of circulating DNA fragments in the extracted maternal cell-free DNA. The presented approach could be useful in the presequencing stage of noninvasive prenatal testing to evaluate whether the sample is suitable for the test or a repeat blood draw is recommended.

Thiamine metabolism dysfunction syndrome-4 (THMD4) includes episodic encephalopathy, often associated with a febrile illness, causing transient neurologic dysfunction and a slowly progressive axonal polyneuropathy. Until now only two mutations (G125S and S194P) have been reported in the SLC25A19gene as causative for this disease and a third mutation (G177A) as related to the Amish lethal microcephaly. In this work, we describe the clinical and molecular features of a patient carrying a novel mutation (c.576G>C; Q192H) on SLC25A19gene. Functional studies on this mutation were performed explaining the pathogenetic role of c.576G>C in affecting the translational efficiency and/or stability of hMTPPT protein instead of the mRNA expression. These findings support the pathogenetic role of Q192H (c.576G>C) mutation on SLC25A19gene. Moreover, despite in other patients the thiamine supplementation leaded to a substantial improvement of peripheral neuropathy, our patient did not show a clinical improvement.

Aim:The objective of this study was to investigate the possible synergy between doxycycline and photodynamic therapy against Helicobacter pyloriand to evaluate the possible side effects on adenocarcinoma gastric cells with and without protoporphyrin IX. Materials & methods:Three H. pyloristrains (ATCC 700392, 43504 and 49503) were grown on solid medium either with, or without, doxycycline at subinhibitory concentrations, and irradiated for 10, 20 and 30 minutes with a 400 nm-peaked light source. The phototoxicity tests on AGS cells were evaluated by MTT assay. Results:The photodynamic therapy and doxycycline combination showed an antibacterial synergistic effect with no significant toxicities. Conclusion:The synergistic treatment could be considered as an interesting therapeutic option.

The knowledge about ovarian physiology in small ruminants is still limited, especially when compared to other domestic species. Ovarian function in goats is mainly assessed by ultrasonographic techniques, whereas a quali-quantitative feature of the follicular and luteal structures throughout the reproductive cycle in naturally cycling goats is scarce. This study provides a detailed description of the functional morphology and size of 742 ovarian structures (follicles, corpora hemorrhagicaand corpora lutea) in relation to the oestrus phase, the body weight and the age of 25 Alpine goats (Capra hircus). The current study demonstrated that, the number and size of the follicles were related to the stage of the reproductive cycle (P < 0.0001). Also, the mean number of follicles was high during both prepubertal anestrus and diestrus, whereas it was low in the oestrus. Large (3-4 mm in diameter) and very large follicles (> 4 mm) (P < 0.001), and small follicles (< 2 mm; P < 0.05) varied throughout the reproductive cycle, while medium follicles (2-3 mm) were invariably observed. Large and very large follicles were predominant during the diestrus phase and small follicles in the prepubertal anestrus. It is evident from the current study that the number of follicles (P < 0.05) was significantly affected with both body weight and age. On the other hand, the size of follicles was significantly affected with body weight only (P < 0.0001). These results could contribute to a deeper understanding of ovarian transformations with important implications in assisted reproductive technologies, thereby concurring in advancing the efficiency of ultrasound in breeding programs for this species.

ABSTRACTThe identification of multilocus imprinting disturbances (MLID) appears fundamental to uncover molecular pathways underlying imprinting disorders (IDs) and to complete clinical diagnosis of patients. However, MLID genetic associated mechanisms remain largely unknown. To characterize MLID in Beckwith-Wiedemann (BWS) and Silver-Russell (SRS) syndromes, we profiled by MassARRAY the methylation of 12 imprinted differentially methylated regions (iDMRs) in 21 BWS and 7 SRS patients with chromosome 11p15.5 epimutations. MLID was identified in 50% of BWS and 29% of SRS patients as a maternal hypomethylation syndrome. By next-generation sequencing, we searched for putative MLID-causative mutations in genes involved in methylation establishment/maintenance and found two novel missense mutations possibly causative of MLID: one in NLRP2, affecting ADP binding and protein activity, and one in ZFP42, likely leading to loss of DNA binding specificity. Both variants were paternally inherited. In silicoprotein modelling allowed to define the functional effect of these mutations. We found that MLID is very frequent in BWS/SRS. In addition, since MLID-BWS patients in our cohort show a peculiar pattern of BWS-associated clinical signs, MLID test could be important for a comprehensive clinical assessment. Finally, we highlighted the possible involvement of ZFP42variants in MLID development and confirmed NLRP2as causative locus in BWS-MLID.

Syndromes caused by copy number variations are described as reciprocal when they result from deletions or duplications of the same chromosomal region. When comparing the phenotypes of these syndromes, various clinical features could be described as reversed, probably due to the opposite effect of these imbalances on the expression of genes located at this locus. The NFIXgene codes for a transcription factor implicated in neurogenesis and chondrocyte differentiation. Microdeletions and loss of function variants of NFIXare responsible for Sotos syndrome-2 (also described as Malan syndrome), a syndromic form of intellectual disability associated with overgrowth and macrocephaly. Here, we report a cohort of nine patients harboring microduplications encompassing NFIX. These patients exhibit variable intellectual disability, short stature and small head circumference, which can be described as a reversed Sotos syndrome-2 phenotype. Strikingly, such a reversed phenotype has already been described in patients harboring microduplications encompassing NSD1, the gene whose deletions and loss-of-function variants are responsible for classical Sotos syndrome. Even though the type/contre-typeconcept has been criticized, this model seems to give a plausible explanation for the pathogenicity of 19p13 microduplications, and the common phenotype observed in our cohort.

This report shows for the first time clinical imaging (ultrasound and computed tomography), histological and immunohistochemical findings of an ovarian leiomyoma, coincidentally diagnosed in an asymptomatic unmated nulliparous ten year-old German shepherd bitch concurrently suffering from multiple mammary tumors. A thorough examination allowed the differentiation of ovarian leiomyoma from other spindle cell tumors. An accurate description of the diagnostic procedures useful in the managing of ovarian leiomyoma could provide valuable information to veterinary practitioners. Indeed, despite its rarity and nonspecific symptoms, ovarian leiomyoma may also affect the dog with an unknown potential risk.

ABSTRACTMicrobiological tests on cerebrospinal fluid (CSF) utilize a common urgent-care procedure that does not take into account the chemical and cytological characteristics of the CSF, resulting sometimes in an unnecessary use of human and diagnostic resources. The aim of this study was to retrospectively validate a simple scoring system (bacterial meningitis-Careggi score [BM-CASCO]) based on blood and CSF sample chemical/cytological parameters for evaluating the probability of acute bacterial meningitis (ABM) in adults. BM-CASCO (range, 0 to 6) was defined by the following parameters: CSF cell count, CSF protein levels, CSF lactate levels, CSF glucose-to-serum glucose ratio, and peripheral neutrophil count. BM-CASCO was retrospectively calculated for 784 cases of suspected ABM in adult subjects observed during a four-and-a-half-year-period (2010 to 2014) at the emergency department (ED) of a large tertiary-care teaching hospital in Italy. Among the 28 confirmed ABM cases (3.5%), Streptococcus pneumoniaewas the most frequent cause (16 cases). All ABM cases showed a BM-CASCO value of =3. Most negative cases (591/756) exhibited a BM-CASCO value of =1, which was adopted in our laboratory as a cutoff to not proceed with urgent microbiological analysis of CSF in cases of suspected ABM in adults. During a subsequent 1-year follow-up, the introduction of the BM-CASCO in the diagnostic workflow of ABM in adults resulted in a significant decrease in unnecessary microbiological analysis, with no false negatives. In conclusion, BM-CASCO appears to be an accurate and simple scoring system for optimization of the microbiological diagnostic workflow of ABM in adults.

The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees.

A subset of patients with KIT/PDGFRAwild-type gastrointestinal stromal tumors show loss of function of succinate dehydrogenase, mostly due to germ-line mutations of succinate dehydrogenase subunits, with a predominance of succinate dehydrogenase subunit A. The clinical outcome of these patients seems favorable, as reported in small series in which patients were individually described. This work evaluates a retrospective survival analysis of a series of patients with metastatic KIT/PDGFRAwild-type succinate dehydrogenase–deficient gastrointestinal stromal tumors.

Purpose:The harmful effects of inbreeding are well known by geneticists, and several studies have already reported cases of intellectual disability caused by recessive variants in consanguineous families. Nevertheless, the effects of inbreeding on the degree of intellectual disability are still poorly investigated. Here, we present a detailed analysis of the homozygosity regions in a cohort of 612 patients with intellectual disabilities of different degrees.Methods:We investigated (i) the runs of homozygosity distribution between syndromic and nonsyndromic ID (ii) the effect of runs of homozygosity on the ID degree, using the intelligence quotient score.Results:Our data revealed no significant differences in the first analysis; instead we detected significantly larger runs of homozygosity stretches in severe ID compared to nonsevere ID cases (P = 0.007), together with an increase of the percentage of genome covered by runs of homozygosity (P = 0.03).Conclusion:In accord with the recent findings regarding autism and other neurological disorders, this study reveals the important role of autosomal recessive variants in intellectual disability. The amount of homozygosity seems to modulate the degree of cognitive impairment despite the intellectual disability cause.Genet Med 17 5, 396–399.

ABSTRACTWe describe a large hospital outbreak (93 bloodstream infections) of colistin-resistant Klebsiella pneumoniaecarbapenemase (KPC)-producing K. pneumoniaeisolates which was mirrored by increased colistin consumption. The outbreak was mostly traced to the clonal expansion of an mgrBdeletion mutant of an ST512 strain that produced KPC-3.

Introduction. Developmental delay and dysmorphic features affect 1 - 3 % of paediatric population. In the last few years molecular cytogenetic high resolution techniques (comparative genomic hybridization arrays and single-nucleotide polymorphism arrays) have been proven to be a first-tier choice for clinical diagnostics of developmental delay and dysmorphic features.

Background:Tramadol is a synthetic codeine analogue used as an analgesic in human and veterinary medicine. It is not approved for use in horses, but could represent a valid tool for pain treatment in this species.Objectives:The serum pharmacokinetic profile and urinary excretion of tramadol and its metabolites (O-desmethyltramadol [M1], N-desmethyltramadol [M2] and N,O-desmethyltramadol [M5]) was investigated in a multidrug anaesthetic and analgesic approach for orchiectomy in horses. The evaluation of the degree of cardiovascular stability, the intraoperative effect and postoperative analgesia obtained by the visual analogue scale are also reported.Animal and methods:Tramadol (4 mg/kg BW) was administered intravenously to eight male yearlings as a bolus over 60 seconds, 5 min after intubation and 15 min prior to surgery. Drug quantification was performed in serum and urine for tramadol, M1, M2 and M5 by high-performance liquid chromatography with fluorimetric detection.Results:Mean tramadol concentration was 14.87 ± 11.14 μg/mL at 0.08 h, and 0.05 ± 0.06 μg/mL at 10 h. Serum concentrations of M1 and M2 metabolites were quite limited. For M1 and M2, median maximum concentration (Cmax) and time to achieve maximum concentration (Tmax) were 0.05 μg/mL and 0.75 h, and 0.08 μg/mL and 2 h, respectively; M5 was never detected. In urine, tramadol was the most recovered compound, followed by M1, M2 and M5.Conclusions and clinical relevance:Showing no adverse events and based on the kinetic behaviour, pre-operative tramadol IV at a dose of 4 mg/kg BW might be useful and safe as analgesic in horses undergoing surgery.

Background: Translational medicine aims at transferring advances in basic science research into new approaches for diagnosis and treatment of diseases. Low‐grade gliomas (LGG) have a heterogeneous clinical behavior that can be only partially predicted employing current state‐of‐the‐art markers, hindering the decision‐making process. To deepen our comprehension on tumor heterogeneity, we dissected the mechanism of interaction between tumor cells and relevant components of the neoplastic environment, isolating, from LGG and high‐grade gliomas (HGG), proliferating stem cell lines from both the glioma stroma and, where possible, the neoplasm. Methods and Findings: We isolated glioma‐associated stem cells (GASC) from LGG (n=40) and HGG (n=73). GASC showed stem cell features, anchorage‐independent growth, and supported the malignant properties of both A172 cells and human glioma‐stem cells, mainly through the release of exosomes. Finally, starting from GASC obtained from HGG (n=13) and LGG (n=12) we defined a score, based on the expression of 9 GASC surface markers, whose prognostic value was assayed on 40 subsequent LGG‐patients. At the multivariate Cox analysis, the GASC‐based score was the only independent predictor of overall survival and malignant progression free‐survival. Conclusions: The microenvironment of both LGG and HGG hosts non‐tumorigenic multipotent stem cells that can increase in vitrothe biological aggressiveness of glioma‐initiating cells through the release of exosomes. The clinical importance of this finding is supported by the strong prognostic value associated with the characteristics of GASC. This patient‐based approach can provide a groundbreaking method to predict prognosis and to exploit novel strategies that target the tumor stroma. StemCells2014;32:1239–1253

ABSTRACTAcquired metallo-β-lactamases (MBLs) are resistance determinants of increasing clinical importance in Gram-negative bacterial pathogens, which confer a broad-spectrum β-lactam resistance, including carbapenems. Several such enzymes have been described since the 1990s. In the present study, a novel acquired MBL, named FIM-1, was identified and characterized. The blaFIM-1gene was cloned from a multidrug-resistant Pseudomonas aeruginosaclinical isolate (FI-14/157) cultured from a patient with a vascular graft infection in Florence, Italy. The isolate belonged in the sequence type 235 epidemic clonal lineage. The FIM-1 enzyme is a member of subclass B1 and, among acquired MBLs, exhibited the highest similarity (ca. 40% amino acid identity) with NDM-type enzymes. In P. aeruginosaFI-14/157, the blaFIM-1gene was apparently inserted into the chromosome and associated with ISCR19-like elements that were likely involved in the capture and mobilization of this MBL gene. Transfer experiments of the blaFIM-1gene to an Escherichia colistrain or another P. aeruginosastrain by conjugation or electrotransformation were not successful. The FIM-1 protein was produced in E. coliand purified by two chromatography steps. Analysis of the kinetic parameters, carried out with the purified enzyme, revealed that FIM-1 has a broad substrate specificity, with a preference for penicillins (except the 6α-methoxy derivative temocillin) and carbapenems. Aztreonam was not hydrolyzed. Detection of this novel type of acquired MBL in a P. aeruginosaclinical isolate underscores the increasing diversity of such enzymes that can be encountered in the clinical setting.

Toxoplasma gondiiis an opportunistic parasite, which very unusually may cause acute encephalitis in patients undergoing chemotherapy or hematopoietic stem cell transplant. The prognosis is usually dismal also because of late diagnosis, depending on the limited availability of specific diagnostic tools. An early diagnosis allows effective intervention with specific antibiotics, which may provide a chance for cure. We report 2 cases of cerebral toxoplasmosis in which the use of polymerase chain reaction on cerebrospinal fluid allowed a prompt diagnosis and specific therapy, which was followed by clinical response and negativization at follow-up studies of T. gondiigenome on cerebrospinal fluid by polymerase chain reaction and by brain imaging.

We studied the floristic composition in the pastures of the Southern Alps (Trento Province, Italy). One hundred and five plots in seven different pasture plant communities were sampled: (1) nitrophilous, (2) montane mesic, (3) subalpine mesic, (4) calcareous montane, (5) calcareous subalpine, (6) acid montane, and (7) acid subalpine pastures. Forward selection and variation partitioning were applied to identify the most important factors controlling the species composition and plant traits in the pastures. Aggregated weighted averages were calculated for each plot using the published values of average height, specific leaf area, and seed mass for each species. Explanatory variables were recorded for each site to reflect climate, soil properties, and grazing pressure. We hypothesised that species composition and functional variation in pastures of the Southern Alps are controlled by three main environmental filters: climate, resource availability, and grazing pressure. We found that variables of climate and soil properties had a major role in explaining the species composition and variations in plant traits, while grazing pressure showed a lower independent effect. Species composition and plant traits depended mainly on temperature, soil fertility, and variables of bedrock type — soil pH. Our results confirm the importance of taking the effects of climate and resource availability into account when describing plant and community functions of grasslands.

We studied the floristic composition in the pastures of the Southern Alps (Trento Province, Italy). One hundred and five plots in seven different pasture plant communities were sampled: (1) nitrophilous, (2) montane mesic, (3) subalpine mesic, (4) calcareous montane, (5) calcareous subalpine, (6) acid montane, and (7) acid subalpine pastures. Forward selection and variation partitioning were applied to identify the most important factors controlling the species composition and plant traits in the pastures. Aggregated weighted averages were calculated for each plot using the published values of average height, specific leaf area, and seed mass for each species. Explanatory variables were recorded for each site to reflect climate, soil properties, and grazing pressure. We hypothesised that species composition and functional variation in pastures of the Southern Alps are controlled by three main environmental filters: climate, resource availability, and grazing pressure. We found that variables of climate and soil properties had a major role in explaining the species composition and variations in plant traits, while grazing pressure showed a lower independent effect. Species composition and plant traits depended mainly on temperature, soil fertility, and variables of bedrock type - soil pH. Our results confirm the importance of taking the effects of climate and resource availability into account when describing plant and community functions of grasslands.

ABSTRACTThe strain diversity and the population structure of nosocomial Acinetobacterisolated from patients admitted to different hospitals in Florence, Italy, during a 3-year surveillance program, were investigated by amplified fragment length polymorphism (AFLP). The majority of isolates (84.5%) were identified as A. baumannii, confirming this species as the most common hospital Acinetobacter. Three very distinct A. baumanniiclonal groups (A1, A2, and A3) were defined. The A1 isolates appeared to be genetically related to the well-characterized European EU II clone. A2 was responsible for three outbreaks which occurred in two intensive care units. Space/time population dynamic analysis showed that A1 and A2 were successful nosocomial clones. Most of the A. baumannniiisolates were imipenem resistant. The genetic determinants of carbapenem resistance were investigated by multiplex PCR, showing that resistance, independently of hospital origin, period of isolation, or clonal group, was associated with the presence of a blaOXA-58-likegene and with ISAba2and ISAba3elements flanking this gene. blaOXA-58appeared to be horizontally transferred. This study showed that the high discriminatory power of AFLP is useful for identification and typing of nosocomial Acinetobacterisolates. Moreover the use of AFLP in a real-time surveillance program allowed us the recognition of clinically relevant and widespread clones and their monitoring in hospital settings. The correlation between clone diffusion, imipenem resistance, and the presence of the blaOXA-58-likegene is discussed.

ABSTRACTIn this study we report the results of analysis of 253 isolates of Staphylococcus aureus(132 methicillin [meticillin]-resistant S. aureus[MRSA] isolates and 121 methicillin-susceptible S. aureus[MSSA] isolates) from 209 patients admitted to 18 high-risk wards of six hospitals located in Florence, Italy, over an 8-month period during which a program of epidemiological surveillance of hospital-acquired infections was conducted. The majority (69%) of the 87 reported S. aureusinfections were caused by MRSA. No outbreak events have been reported. All the isolates were typed by amplified fragment length polymorphism (AFLP), and AFLP profiles were analyzed in order to define similarity groups. The discriminatory power of AFLP is very high with MSSA (Simpson index of diversity [D], 95.9%), whereas its resolution capability with MRSA (D, 44.7%) is hampered by the well-known high clonality of these populations (the main MRSA group accounted for 74% of the MRSA isolates). Combining AFLP, improved by visual inspection of polymorphisms, with multiplex PCR greatly increases MRSA resolution (D, 85.5%), resolving the MRSA population to a level that is one of the highest reported in the literature. Widespread and sporadic clones of MSSA and MRSA were identified, and their diffusion in the different hospitals and wards over the surveillance period was studied. The understanding of MSSA and MRSA population structures should be the starting point for the design of a more rational surveillance program for S. aureusspecies, maximizing benefits and reducing the cost of infection control strategies.

ABSTRACTThe objective of this study was to characterize by serotyping, pulsed-field gel electrophoresis (PFGE), and PCR amplification of virulence genes and markers of epidemic clones I, II, and III (ECI, ECII, and ECIII) 54 human isolates from apparently sporadic cases of infection occurring in the Lombardy region and in the province of Florence, Tuscany, Italy, in the years 1996 to 2007. Listeria monocytogenesisolates were provided by the clinical microbiology laboratories of the Lombardy region and the “Careggi” Hospital of Florence, Tuscany, Italy. Serotyping, PFGE after digestion with the AscI and ApaI enzymes, and PCR amplification for the inlA, inlC, and inlJgenes and ECI, ECII, and ECIII markers were performed according to procedures described previously. Twenty-five (46.3%) L. monocytogenesisolates were assigned to serotype 1/2a, 23 (42.6%) to serotype 4b, and 6 (11.1%) to serotype 1/2b. Thirty-one AscI pulsotypes were recognized among the 54 human isolates. Eleven molecular subtype clusters, of which eight included indistinguishable pulsotypes and three included closely related pulsotypes, were shared by two to seven isolates. Fifteen isolates exhibited unique AscI pulsotypes. Three groups of clustered isolates and two apparently sporadic isolates generated EC amplicons. All strains tested positive for the inlA, inlC, and inlJgenes. Based on the results of serotyping and molecular typing, there were 11 occasions when L. monocytogenesstrains with the same subtype were isolated from more than one listeriosis case. A total of 39 out of 54 isolates (72.2%) were attributed to molecular subtype clusters. The results of the study suggest that routine subtyping of L. monocytogenesstrains from human listeriosis cases could allow more-timely detection of outbreaks possibly caused by food-borne isolates from a common source and could lead to control of ongoing food exposure, thus preventing the occurrence of more cases.

In Italy, the annual incidence of reported cases of listeriosis amounts in recent years (2004 to 2006) to 0.8 case per million inhabitants. Our study is a subtyping analysis by serotyping, ribotyping, and pulsed-field gel electrophoresis analysis of 44 human isolates from apparently sporadic cases of infection in the Lombardy region and in the Province of Florence, Italy, in the years 1996 to 2007. Based on the results of the different subtyping methods, 10 occasions were detected when strains of L. monocytogeneswith the same subtype were isolated from more than one listeriosis case. A total of 28 (66.7%) of 44 isolates were attributed to molecular subtype clusters. Our data support the use of sensitive molecular approaches to identify and trace L. monocytogenesisolates responsible for foodborne outbreaks of human listeriosis.

Based on genotype–phenotype correlation analysis of 80 Wolf–Hirschhorn syndrome WHS patients, as well as on review of relevant literature, we add further insights to the following aspects of WHS: 1 clinical delineation and phenotypic categories; 2 characterization of the basic genomic defect, mechanisms of origin and familiarity; 3 identification of prognostic factors for mental retardation; 4 chromosome mapping of the distinctive clinical signs, in an effort to identify pathogenic genes. Clinically, we consider that minimal diagnostic criteria for WHS, defining a “core” phenotype, are typical facial appearance, mental retardation, growth delay and seizures or EEG anomalies. Three different categories of the WHS phenotype were defined, generally correlating with the extent of the 4p deletion. The first one comprises a small deletion not exceeding 3.5 Mb, that is usually associated with a mild phenotype, lacking major malformations. This category is likely underdiagnosed. The second and by far the more frequent category is identified by large deletions, averaging between 5 and 18 Mb, and causes the widely recognizable WHS phenotype. The third clinical category results from a very large deletion exceeding 22–25 Mb causing a severe phenotype, that can hardly be defined as typical WHS. Genetically, de novo chromosome abnormalities in WHS include pure deletions but also complex rearrangements, mainly unbalanced translocations. With the exception of t4p;8p, WHSassociated chromosome abnormalities are neither mediated by segmental duplications, nor associated with a parental inversion polymorphism on 4p16.3. Factors involved in prediction of prognosis include the extent of the deletion, the occurrence of complex chromosome anomalies, and the severity of seizures. We found that the core phenotype maps within the terminal 1.9 Mb region of chromosome 4p. Therefore, WHSCR2 should be considered the critical region for this condition. We also confirmed that the pathogenesis of WHS is multigenic. Specific and independent chromosome regions were characterized for growth delay and seizures, as well as for the additional clinical signs that characterize this condition. With the exception of parental balanced translocations, familial recurrence is uncommon. © 2008 WileyLiss, Inc.

Catheter-related bloodstream infections (CRBSIs) are one of the main morbidities in critically ill neonates. The objective of the present study was to assess the efficacy of a fusidic acid-heparin lock in the prevention of CRBSIs.

The ovaries and uterus were collected after ovariohysterectomy from a 16-month-old Labrador bitch in diestrus that never mated. Discrete swellings were found in the uterine horns, with the macroscopic appearance of normal early pregnancy. At histologic examination, the endometrium, devoid of any conceptus and chorion, showed a marked proliferation, on the basis of which a diagnosis of deciduoma was made. A remarkable population of stromal eosinophilic granular lymphocytes was present, especially in the axis of the endometrial folds. Periodic acid-Schiff and Dolichos biflorus-lectin histochemical reaction and a panel of 10 immunohistochemical markers were used to characterize eosinophilic granular cells. Our findings allowed us to compare these granular cells with the granulated decidual cells, whose presence was until now described only in primates, rodents, or a few other epitheliochorial species. On the basis of our results, the importance of eosinophilic granular cells in a decidualization process is hypothesized to occur also in the bitch.

In the past few years, procalcitonin has been proposed as a sensitive and specific inflammatory marker in various fields of medicine, especially in infectivology, where it has been used to discriminate between bacterial infections, viral infections and inflammation processes. Recently, different studies have emerged in the literature on the use of this marker to identify renal involvement in febrile urinary tract infections.

We report the epidemiological investigation of an outbreak of Pseudomonas aeruginosainfection in 6 patients who shared, during different periods, the same 2 rooms of a bone marrow transplantation unit. Phenotypic and molecular analysis of isolates from patients and from the environment strongly suggested a single, environmental source of infection.

Purpose: We evaluated the experiences of 19 Italian laboratories concerning 241 small supernumerary marker chromosomes (sSMCs) with the aim of answering questions arising from their origin from any chromosome, their variable size and genetic content, and their impact on the carrier's phenotype.Methods: Conventional protocols were used to set up the cultures and chromosome preparations. Both commercial and homemade probes were used for the fluorescent in situ hybridization analyses.Results: A total of 113 of the 241 sSMCs were detected antenatally, and 128 were detected postnatally. There were 52 inherited and 172 de novo cases. Abnormal phenotype was present in 137 cases (57%), 38 of which were antenatally diagnosed. A mosaic condition was observed in 87 cases (36%). In terms of morphology, monocentric and dicentric bisatellited marker chromosomes were the most common, followed by monocentric rings and short-arm isochromosomes. The chromosomes generating the sSMCs were acrocentric in 132 cases (69%) and non-acrocentric chromosomes in 60 cases (31%); a neocentromere was hypothesized in three cases involving chromosomes 6, 8, and 15.Conclusion: The presented and published data still do not allow any definite conclusions to be drawn concerning karyotype–phenotype correlations. Only concerted efforts to characterize molecularly the sSMCs associated or not with a clinical phenotype can yield results suitable for addressing karyotype–phenotype correlations in support of genetic counseling.