Global status of gene edited animals for agricultural applications.

Gene editing (GnEd) involves using a site-directed nuclease to introduce a double-strand break (DSB) at a targeted location in the genome. A literature search was performed on the use of GnEd in animals for agricultural applications. Data was extracted from 212 peer-reviewed articles that described the production of at least one living animal employing GnEd technologies for agricultural purposes. The most common GnEd system reported was CRISPR/Cas9, and the most frequent type of edit was the unguided insertion or deletion resulting from the repair of the targeted DSB leading to a knock-out (KO) mutation. Animal groups included in the reviewed papers were ruminants (cattle, sheep, goats, n=63); monogastrics (pigs and rabbits, n=60); avian (chicken, duck, quail, n=17); aquatic (many species, n=65), and insects (honeybee, silkworm, n=7). Yield (32%), followed by reproduction (21%) and disease resistance (17%) were the most commonly targeted traits. Over half of the reviewed papers had Chinese first-authorship. Several countries, including Argentina, Australia, Brazil, Colombia and Japan, have adopted a regulatory policy that considers KO mutations introduced following GnEd DSB repair as akin to natural genetic variation, and therefore treat these GnEd animals analogously to those produced using conventional breeding. This approach has resulted in a non-GMO determination for a small number of GnEd food animal applications, including three species of GnEd KO fast-growing fish, (red sea bream, olive flounder and tiger pufferfish in Japan), KO fish and cattle in Argentina and Brazil, and porcine reproductive and respiratory syndrome (PRRS) virus disease-resistant KO pigs in Colombia.

Germline ablation achieved via CRISPR/Cas9 targeting of NANOS3 in bovine zygotes.

NANOS3 is expressed in migrating primordial germ cells (PGCs) to protect them from apoptosis, and it is known to be a critical factor for germline development of both sexes in several organisms. However, to date, live NANOS3 knockout (KO) cattle have not been reported, and the specific role of NANOS3 in male cattle, or bulls, remains unexplored. This study generated NANOS3 KO cattle via cytoplasmic microinjection of the CRISPR/Cas9 system in vitro produced bovine zygotes and evaluated the effect of NANOS3 elimination on bovine germline development, from fetal development through reproductive age. The co-injection of two selected guide RNA (gRNA)/Cas9 ribonucleoprotein complexes (i.e., dual gRNA approach) at 6 h post fertilization achieved a high NANOS3 KO rate in developing embryos. Subsequent embryo transfers resulted in a 31% (n = 8/26) pregnancy rate. A 75% (n = 6/8) total KO rate (i.e., 100% of alleles present contained complete loss-of-function mutations) was achieved with the dual gRNA editing approach. In NANOS3 KO fetal testes, PGCs were found to be completely eliminated by 41-day of fetal age. Importantly, despite the absence of germ cells, seminiferous tubule development was not impaired in NANOS3 KO bovine testes during fetal, perinatal, and adult stages. Moreover, a live, NANOS3 KO, germline-ablated bull was produced and at sexual maturity he exhibited normal libido, an anatomically normal reproductive tract, and intact somatic gonadal development and structure. Additionally, a live, NANOS3 KO, germline-ablated heifer was produced. However, it was evident that the absence of germ cells in NANOS3 KO cattle compromised the normalcy of ovarian development to a greater extent than it did testes development. The meat composition of NANOS3 KO cattle was unremarkable. Overall, this study demonstrated that the absence of NANOS3 in cattle leads to the specific deficiency of both male and female germ cells, suggesting the potential of NANOS3 KO cattle to act as hosts for donor-derived exogenous germ cell production in both sexes. These findings contribute to the understanding of NANOS3 function in cattle and have valuable implications for the development of novel breeding technologies using germline complementation in NANOS3 KO germline-ablated hosts.

Review: Progress in producing chimeric ungulate livestock for agricultural applications.

The progress made in recent years in the derivation and culture of pluripotent stem cells from farm animals opens up the possibility of creating livestock chimeras. Chimeras producing gametes exclusively derived from elite donor stem cells could pass superior genetics on to the next generation and thereby reduce the genetic lag that typically exists between the elite breeding sector and the commercial production sector, especially for industries like beef and sheep where genetics is commonly disseminated through natural service mating. Chimeras carrying germ cells generated from genome-edited or genetically engineered pluripotent stem cells could further disseminate useful genomic alterations such as climate adaptation, animal welfare improvements, the repair of deleterious genetic conditions, and/or the elimination of undesired traits such as disease susceptibility to the next generation. Despite the successful production of chimeras with germ cells generated from pluripotent donor stem cells injected into preimplantation-stage blastocysts in model species, there are no documented cases of this occurring in livestock. Here, we review the literature on the derivation of pluripotent stem cells from ungulates, and progress in the production of chimeric ungulate livestock for agricultural applications, drawing on insights from studies done in model species, and discuss future possibilities of this fast-moving and developing field. Aside from the technical aspects, the consistency of the regulatory approach taken by different jurisdictions towards chimeric ungulate livestock with germ cells generated from pluripotent stem cells and their progeny will be an important determinant of breeding industry uptake and adoption in animal agriculture.

Low salinity activates a virulence program in the generalist marine pathogen Photobacterium damselae subsp. damselae.

Facultative marine bacterial pathogens sense environmental signals so that the expression of virulence factors is upregulated on entry into hosts and downregulated during the free-living lifestyle in the environment. In this study, we utilized transcriptome sequencing to compare the transcriptional profiles of Photobacterium damselae subsp. damselae, a generalist pathogen that causes disease in diverse marine animals and fatal infections in humans at NaCl concentrations that mimic the free-living lifestyle or host internal milieu, respectively. We here show that NaCl concentration constitutes a major regulatory signal that shapes the transcriptome and uncover 1,808 differentially expressed genes (888 upregulated and 920 downregulated in response to low-salt conditions). Growth at 3% NaCl, a salinity that mimics the free-living lifestyle, upregulated genes involved in energy production, nitrogen metabolism, transport of compatible solutes, utilization of trehalose and fructose, and carbohydrate and amino acid metabolism with strong upregulation of the arginine deiminase system (ADS). In addition, we observed a marked increase in resistance to antibiotics at 3% NaCl. On the contrary, the low salinity conditions (1% NaCl) that mimic those encountered in the host triggered a virulence gene expression profile that maximized the production of the type 2 secretion system (T2SS)-dependent cytotoxins damselysin, phobalysin P, and a putative PirAB-like toxin, observations that were corroborated by the analysis of the secretome. Low salinity also upregulated the expression of iron-acquisition systems, efflux pumps, and other functions related to stress response and virulence. The results of this study greatly expand our knowledge of the salinity-responsive adaptations of a generalist and versatile marine pathogen. IMPORTANCE Pathogenic Vibrionaceae species experience continuous shifts of NaCl concentration in their life cycles. However, the impact of salinity changes in gene regulation has been studied in a small number of Vibrio species. In this study, we analyzed the transcriptional response of Photobacterium damselae subsp. damselae (Pdd), a generalist and facultative pathogen, to changes in salinity, and demonstrate that growth at 1% NaCl in comparison to 3% NaCl triggers a virulence program of gene expression, with a major impact in the T2SS-dependent secretome. The decrease in NaCl concentration encountered by bacteria on entry into a host is proposed to constitute a regulatory signal that upregulates a genetic program involved in host invasion and tissue damage, nutrient scavenging (notably iron), and stress responses. This study will surely inspire new research on Pdd pathobiology, as well as on other important pathogens of the family Vibrionaceae and related taxa whose salinity regulons still await investigation.

18F-Fluorodeoxyglucose Positron Emission Tomography Parameters can Predict Long-Term Outcome Following Trimodality Treatment for Oesophageal Cancer.

AIMS: 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18FDG-PET/CT) is routinely used for the pre-treatment staging of oesophageal or gastro-oesophageal junction cancers (EGEJC). The aim of this study was to identify objective 18FDG-PET/CT-derived parameters that can aid in predicting the patterns of recurrence and prognostication in patients with EGEJC. PATIENTS AND METHODS: EGEJC patients referred for consideration of preoperative chemoradiation therapy were identified and clinicopathological data were collected. 18FDG-PET/CT imaging data were reviewed and correlated with treatment outcomes. Maximum standardised uptake value (SUVmax), metabolic tumour volume (MTV) and total lesion glycolysis were assessed and association with recurrence-free survival (RFS), locoregional recurrence-free survival (LR-RFS), oesophageal cancer-specific survival (ECSS) and overall survival were evaluated using receiver operating characteristic curves, as well as Cox regression and Kaplan-Meier models. RESULTS: In total, 191 EGEJC patients completed trimodality treatment and 164 with 18FDG-PET/CT data were included in this analysis. At the time of analysis, 15 (9.1%), 70 (42.7%) and two (1.2%) patients were noted to have locoregional, distant and both locoregional and distant metastases, respectively. The median RFS was 30 months (9.6-50.4) and the 5-year RFS was 31.1%. The 5-year overall survival and ECSS were both noted to be 34.8%. Pre-treatment MTV25 > 28.5 cm3 (P = 0.029), MTV40 > 12.4 cm3 (P = 0.018) and MTV50 > 10.2 cm3 (P = 0.005) predicted for worse LR-RFS, ECSS and overall survival for MTV definition of voxels ≥25%, 40% and 50% of SUVmax. CONCLUSION: 18FDG-PET/CT parameters MTV and total lesion glycolysis are useful prognostic tools to predict for LR-RFS, ECSS and overall survival in EGEJC. MTV had the highest accuracy in predicting clinical outcomes. The volume cut-off points we identified for different MTV thresholds predicted outcomes with significant accuracy and may potentially be used for decision making in clinical practice.

Rise and Fall, and Slow Rise Again, of Operator Entanglement under Dephasing.

The operator space entanglement entropy, or simply "operator entanglement" (OE), is an indicator of the complexity of quantum operators and of their approximability by matrix product operators (MPOs). We study the OE of the density matrix of 1D many-body models undergoing dissipative evolution. It is expected that, after an initial linear growth reminiscent of unitary quench dynamics, the OE should be suppressed by dissipative processes as the system evolves to a simple stationary state. Surprisingly, we find that this scenario breaks down for one of the most fundamental dissipative mechanisms: dephasing. Under dephasing, after the initial "rise and fall," the OE can rise again, increasing logarithmically at long times. Using a combination of MPO simulations for chains of infinite length and analytical arguments valid for strong dephasing, we demonstrate that this growth is inherent to a U(1) conservation law. We argue that in an XXZ spin model and a Bose-Hubbard model the OE grows universally as 1/4log_{2}t at long times and as 1/2log_{2}t for a Fermi-Hubbard model. We trace this behavior back to anomalous classical diffusion processes.

Does Loosening the Inclusion Criteria of the CROSS Trial Impact Outcomes in the Curative-Intent Trimodality Treatment of Oesophageal and Gastroesophageal Cancer Patients?

AIM: To determine the efficacy of preoperative chemoradiotherapy as per the CROSS protocol for oesophageal/gastroesophageal junction cancer (OEGEJC), when expanded to patients outside of the inclusion/exclusion criteria defined in the original clinical trial. MATERIALS AND METHODS: Data were collected retrospectively on 229 OEGEJC patients referred for curative-intent preoperative chemoradiotherapy. Outcomes including pathological complete response (pCR), overall survival (OS), cancer-specific survival and recurrence-free survival (RFS) of patients who met CROSS inclusion criteria (MIC) versus those who failed to meet criteria (FMIC) were determined. RESULTS: In total, 42.8% of patients MIC, whereas 57.2% FMIC; 16.6% of patients did not complete definitive surgery. The MIC cohort had higher rates of pCR, when compared with the FMIC cohort (33.3% versus 20.6%, P = 0.039). The MIC cohort had a better RFS, cancer-specific survival and OS compared with the FMIC cohort (P = 0.006, P = 0.004 and P = 0.009, respectively). Age >75 years and pretreatment weight loss >10% were not associated with a poorer RFS (P = 0.541 and 0.458, respectively). Compared with stage I-III patients, stage IVa was associated with a poorer RFS (hazard ratio (HR) = 2.158; 95% confidence interval (CI) = 1.339-3.480, P = 0.001). Tumours >8 cm in length or >5 cm in width had a trend towards worse RFS (HR = 2.060; 95% CI = 0.993-4.274, P = 0.052). CONCLUSION: Our study showed that the robust requirements of the CROSS trial may limit treatment for patients with potentially curable OEGEJC and can be adapted to include patients with a good performance status who are older than 75 years or have >10% pretreatment weight loss. However, the inclusion of patients with celiac nodal metastases or tumours >8 cm in length or >5 cm in width may be associated with poor outcomes.

A Secreted NlpC/P60 Endopeptidase from Photobacterium damselae subsp. piscicida Cleaves the Peptidoglycan of Potentially Competing Bacteria.

Peptidoglycan (PG) is a major component of the bacterial cell wall, forming a mesh-like structure enwrapping the bacteria that is essential for maintaining structural integrity and providing support for anchoring other components of the cell envelope. PG biogenesis is highly dynamic and requires multiple enzymes, including several hydrolases that cleave glycosidic or amide bonds in the PG. This work describes the structural and functional characterization of an NlpC/P60-containing peptidase from Photobacterium damselae subsp. piscicida (Phdp), a Gram-negative bacterium that causes high mortality of warm-water marine fish with great impact for the aquaculture industry. PnpA ( PhotobacteriumNlpC-like protein A) has a four-domain structure with a hydrophobic and narrow access to the catalytic center and specificity for the γ-d-glutamyl-meso-diaminopimelic acid bond. However, PnpA does not cleave the PG of Phdp or PG of several Gram-negative and Gram-positive bacterial species. Interestingly, it is secreted by the Phdp type II secretion system and degrades the PG of Vibrio anguillarum and Vibrio vulnificus This suggests that PnpA is used by Phdp to gain an advantage over bacteria that compete for the same resources or to obtain nutrients in nutrient-scarce environments. Comparison of the muropeptide composition of PG susceptible and resistant to the catalytic activity of PnpA showed that the global content of muropeptides is similar, suggesting that susceptibility to PnpA is determined by the three-dimensional organization of the muropeptides in the PG.IMPORTANCE Peptidoglycan (PG) is a major component of the bacterial cell wall formed by long chains of two alternating sugars interconnected by short peptides, generating a mesh-like structure that enwraps the bacterial cell. Although PG provides structural integrity and support for anchoring other components of the cell envelope, it is constantly being remodeled through the action of specific enzymes that cleave or join its components. Here, it is shown that Photobacterium damselae subsp. piscicida, a bacterium that causes high mortality in warm-water marine fish, produces PnpA, an enzyme that is secreted into the environment and is able to cleave the PG of potentially competing bacteria, either to gain a competitive advantage and/or to obtain nutrients. The specificity of PnpA for the PG of some bacteria and its inability to cleave others may be explained by differences in the structure of the PG mesh and not by different muropeptide composition.

Diverse Horizontally-Acquired Gene Clusters Confer Sucrose Utilization to Different Lineages of the Marine Pathogen Photobacterium damselae subsp. damselae.

The ability to metabolize sucrose is a variable trait within the family Vibrionaceae. The marine bacterium Photobacterium damselae subsp. damselae (Pdd), pathogenic for marine animals and humans, is generally described as negative for sucrose utilization (Scr-). Previous studies have reported sucrose-utilizing isolates (Scr+), but the genetic basis of this variable phenotype remains uncharacterized. Here, we carried out the genome sequencing of five Scr+ and two Scr- Pdd isolates and conducted a comparative genomics analysis with sixteen additional Pdd genomes sequenced in previous studies. We identified two different versions of a four-gene cluster (scr cluster) exclusive of Scr+ isolates encoding a PTS system sucrose-specific IIBC component (scrA), a fructokinase (scrK), a sucrose-6-phosphate hydrolase (scrB), and a sucrose operon repressor (scrR). A scrA deletion mutant did not ferment sucrose and was impaired for growth with sucrose as carbon source. Comparative genomics analyses suggested that scr clusters were acquired by horizontal transfer by different lineages of Pdd and were inserted into a recombination hot-spot in the Pdd genome. The incongruence of phylogenies based on housekeeping genes and on scr genes revealed that phylogenetically diverse gene clusters for sucrose utilization have undergone extensive horizontal transfer among species of Vibrio and Photobacterium.

Operator Entanglement in Interacting Integrable Quantum Systems: The Case of the Rule 54 Chain.

In a many-body quantum system, local operators in the Heisenberg picture O(t)=e^{iHt}Oe^{-iHt} spread as time increases. Recent studies have attempted to find features of that spreading which could distinguish between chaotic and integrable dynamics. The operator entanglement-the entanglement entropy in operator space-is a natural candidate to provide such a distinction. Indeed, while it is believed that the operator entanglement grows linearly with time t in chaotic systems, we present evidence that it grows only logarithmically in generic interacting integrable systems. Although this logarithmic growth has been previously established for noninteracting fermions, there has been no progress on interacting integrable systems to date. In this Letter we provide an analytical upper bound on operator entanglement for all local operators in the "Rule 54" qubit chain, a cellular automaton model introduced in the 1990s [Bobenko et al., CMP 158, 127 (1993)CMPHAY0010-361610.1007/BF02097234], and recently advertised as the simplest representative of interacting integrable systems. Physically, the logarithmic bound originates from the fact that the dynamics of the models is mapped onto the one of stable quasiparticles that scatter elastically. The possibility of generalizing this scenario to other interacting integrable systems is briefly discussed.

The RstAB System Impacts Virulence, Motility, Cell Morphology, Penicillin Tolerance and Production of Type II Secretion System-Dependent Factors in the Fish and Human Pathogen Photobacterium damselae subsp. damselae.

The RstB histidine kinase of the two component system RstAB positively regulates the expression of damselysin (Dly), phobalysin P (PhlyP) and phobalysin C (PhlyC) cytotoxins in the fish and human pathogen Photobacterium damselae subsp. damselae, a marine bacterium of the family Vibrionaceae. However, the function of the predicted cognate response regulator RstA has not been studied so far, and the role of the RstAB system in other cell functions and phenotypes remain uninvestigated. Here, we analyzed the effect of rstA and rstB mutations in cell fitness and in diverse virulence-related features. Both rstA and rstB mutants were severely impaired in virulence for sea bream and sea bass fish. Mutants in rstA and rstB genes were impaired in hemolysis and in Dly-dependent phospholipase activity but had intact PlpV-dependent phospholipase and ColP-dependent gelatinase activities. rstA and rstB mutants grown at 0.5% NaCl exhibited impaired swimming motility, enlarged cell size and impaired ability to separate after cell division, whereas at 1% NaCl the mutants exhibited normal phenotypes. Mutation of any of the two genes also impacted tolerance to benzylpenicillin. Notably, rstA and rstB mutants showed impaired secretion of a number of type II secretion system (T2SS)-dependent proteins, which included the three major cytotoxins Dly, PhlyP and PhlyC, as well as a putative delta-endotoxin and three additional uncharacterized proteins which might constitute novel virulence factors of this pathogenic bacterium. The analysis of the T2SS-dependent secretome of P. damselae subsp. damselae also led to the identification of RstAB-independent potential virulence factors as lipoproteins, sialidases and proteases. The RstAB regulon included plasmid, chromosome I and chromosome II-encoded genes that showed a differential distribution among isolates of this subspecies. This study establishes RstAB as a major regulator of virulence and diverse cellular functions in P. damselae subsp. damselae.

A sparsity-controlled vector autoregressive model.

Vector autoregressive (VAR) models constitute a powerful and well studied tool to analyze multivariate time series. Since sparseness, crucial to identify and visualize joint dependencies and relevant causalities, is not expected to happen in the standard VAR model, several sparse variants have been introduced in the literature. However, in some cases it might be of interest to control some dimensions of the sparsity, as e.g. the number of causal features allowed in the prediction. To authors extent none of the existent methods endows the user with full control over the different aspects of the sparsity of the solution. In this article, we propose a versatile sparsity-controlled VAR model which enables a proper visualization of potential causalities while allows the user to control different dimensions of the sparsity if she holds some preferences regarding the sparsity of the outcome. The model coefficients are found as the solution to an optimization problem, solvable by standard numerical optimization routines. The tests performed on both simulated and real-life time series show that our approach may outperform a greedy algorithm and different Lasso approaches in terms of prediction errors and sparsity.

Major phenolic and volatile compounds and their influence on sensorial aspects in stem-contact fermentation winemaking of Primitivo red wines.

In red winemaking de-stemming is crucial since the stems contain polymeric phenolic compounds responsible for the astringency of wine. Wine such as Primitivo has low phenolic constituents and tannins and stems affect aroma, taste body and olfactory characteristics. The aim of the study was to evaluate the effects of presence of stems during fermentation on polyphenolic, volatile compounds and sensory characteristics of wine. Primitivo grapes vinified in presence of different percentage of stems: 100 % de-stemmed (D100), 75 % de-stemmed (D75) and 50 % de-stemmed (D50). Results confirmed that the wines vinified in presence of stems were higher in tannins, flavans, to vanillin and proanthocyanidins, colour intensity with lower anthocyanins. The presence of stems during fermentation conferred more structure and flavour to wines. They facilitated must aeration thus promoting synthesis of higher alcohols and ethyl esters by yeast. In particular, a higher content of hexan-1-ol, hex-3-en-1-ol and 2-phenyl ethanol in D50 and D75 gave the wines that suggest green grass, herb and floral. Wine from D75 seemed to be better than D50 in terms of volatile compounds as well as fruity, floral and balsamic components preserved, without any unpleasant taste of long chain fatty acids found in D50.

HIV/antiretroviral therapy-related lipodystrophy syndrome (HALS) is associated with higher RBP4 and lower omentin in plasma.

Very little information is available on the involvement of newly characterized adipokines in human immunodeficiency virus (HIV)/antiretroviral therapy (ART)-associated lipodystrophy syndrome (HALS). Our aim was to determine whether apelin, apelin receptor, omentin, RBP4, vaspin and visfatin genetic variants and plasma levels are associated with HALS. We performed a cross-sectional multicentre study that involved 558 HIV type 1-infected patients treated with a stable highly active ART regimen, 240 of which had overt HALS and 318 who did not have HALS. Epidemiologic and clinical variables were determined. Polymorphisms in the apelin, omentin, RBP4, vaspin and visfatin genes were assessed by genotyping. Plasma apelin, apelin receptor, omentin, RBP4, vaspin and visfatin levels were determined by enzyme-linked immunosorbent assay in 163 patients (81 with HALS and 82 without HALS) from whom stored plasma samples were available. Student's t test, one-way ANOVA, chi-square test, Pearson and Spearman correlations and linear regression analysis were used for statistical analyses. There were no associations between the different polymorphisms assessed and the HALS phenotype. Circulating RBP4 was significantly higher (p < 0.001) and plasma omentin was significantly lower (p 0.001) in patients with HALS compared to those without HALS; differences in plasma levels of the remaining adipokines were nonsignificant between groups. Circulating RBP4 concentration was predicted independently by the presence of HALS. Apelin and apelin receptor levels were independently predicted by body mass index. Visfatin concentration was predicted independently by the presence of acquired immunodeficiency syndrome. HALS is associated with higher RBP4 and lower omentin in plasma. These two adipokines, particularly RBP4, may be a link between HIV/ART and fat redistribution syndromes.

Molecular epidemiology of Laguna Negra virus, Mato Grosso State, Brazil.

We associated Laguna Negra virus with hantavirus pulmonary syndrome in Mato Grosso State, Brazil, and a previously unidentified potential host, the Calomys callidus rodent. Genetic testing revealed homologous sequencing in specimens from 20 humans and 8 mice. Further epidemiologic studies may lead to control of HPS in Mato Grosso State.

A study of fatty acid binding protein 4 in HIV-1 infection and in combination antiretroviral therapy-related metabolic disturbances and lipodystrophy.

OBJECTIVE: The aim of the study was to determine circulating levels of fatty acid binding protein 4 (FABP-4) in a cohort of HIV-1-infected patients treated with combination antiretroviral therapy (cART) and to investigate the relationships between FABP-4 levels and insulin resistance, dyslipidaemia, lipodystrophy and levels of proinflammatory adipocytokines in these patients. METHODS: A total of 282 HIV-1-infected patients treated with stable cART for at least 1 year (132 with lipodystrophy and 150 without) and 185 uninfected controls (UCs) were included in the study. Anthropometric parameters were determined. Plasma levels of FABP-4, soluble tumour necrosis factor receptors 1 and 2 (sTNF-R1 and sTNF-R2), interleukin-18 (IL-18), IL-6, adiponectin and leptin were also analysed. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). Subcutaneous adipose tissue mRNA expression of proinflammatory cytokines was assessed in 38 patients (25 with lipodystrophy and 13 without) by real-time polymerase chain reaction (PCR). RESULTS: The plasma FABP-4 concentration was significantly higher in patients with lipodystrophy than in those without (P=0.012). FABP-4 concentration was positively correlated with body mass index (BMI), HOMA-IR, and the concentrations of insulin, total cholesterol, triglycerides, sTNF-R1, leptin and IL-18, but showed a negative correlation with high-density lipoprotein (HDL) cholesterol and adiponectin concentrations. After adjusting for age, sex and BMI, the odds ratio (OR) for risk of lipodystrophy was found to be significantly increased for those with the highest levels of FABP-4 [OR 0.838, 95% confidence interval (CI) 0.435-1.616 for medium FABP-4 vs. OR 2.281, 95% CI 1.163-4.475 for high FABP-4]. In a stepwise regression model, FABP-4 was independently associated with HOMA-IR after controlling for clinical and inflammatory parameters (P=0.004). Moreover, a positive relationship was observed in patients with lipodystrophy between subcutaneous adipose tissue CD68 expression and FABP-4 plasma levels (r=0.525; P=0.031). CONCLUSIONS: cART-treated HIV-1-infected patients with lipodystrophy have a systemic overproduction of FABP-4, which is closely linked to insulin resistance and inflammatory markers in subcutaneous adipose tissue.

Two chromosomally located qnrB variants, qnrB6 and the new qnrB16, in Citrobacter spp. isolates causing bacteraemia.

The objective of this study was to determine the prevalence of the plasmid-borne quinolone resistance genes qnrA, qnrB and qnrS in a collection of Enterobacteriaceae causing bacteraemia. The presence of the three genes was tested for using multiplex PCR in 306 clinical isolates. Plasmid analysis was performed using I-CeuI and S1 nuclease digestion and hybridization with specific probes for the qnr and 23S rRNA genes. Five strains were found to carry a qnr gene, one of which, qnrB16, a new variant of qnrB, was detected in a Citrobacter freundii isolate. The qnrB6 variant was found in two C. freundii isolates and in one Citrobacter werkmanii isolate. The qnrS2 gene was found in one Klebsiella pneumoniae isolate. The qnrA gene was not found in any of the isolates studied. The qnrS2 gene was located on a plasmid of c. 50 kb, whereas qnrB6 and qnrB16 were inserted in the chromosome between pspF and the orf2, which had previously been found in a complex integron. In the Hospital Clinic of Barcelona, Spain, the prevalence of qnrB was higher than that of qnrA and qnrS. The importance of the description of the new qnrB16 is emphasized.

Intake of soluble fibers has a protective role for the presence of metabolic syndrome in patients with type 2 diabetes.

BACKGROUND/OBJECTIVES: Dietary factors have been associated with metabolic syndrome (MS) in healthy individuals and specific ethnic groups. To evaluate possible associations of usual dietary factors with the presence of MS in patients with type 2 diabetes mellitus (DM). SUBJECTS/METHODS: In this cross-sectional study, 214 patients with type 2 DM without dietary counseling during previous 6 months were studied. After clinical and laboratory examinations, dietary intake was evaluated by 3-day weighed-diet records, whose reliability was confirmed by 24-h urinary nitrogen output. The presence of MS was defined according to International Diabetes Federation. RESULTS: Patients with MS (n=174) had a lower intake of total (16.7 +/- 6.2 vs 19.5 +/- 6.5 g day(-1); P=0.010) and soluble fibers (5.3 +/- 1.8 vs 6.0 +/- 2.7 g day(-1); P=0.011) than patients without MS. In multiple logistic regression models, adjusted for gender and DM duration, variables associated with MS were soluble fibers (OR=0.86; 95% CI=0.74-0.98; P=0.046), soluble fibers from whole-grain foods (OR=0.43; 95% CI=0.25-0.76; P=0.002) and soluble fibers from fruits (OR=0.76; 95% CI=0.62-0.95; P=0.017). Whole-grain and fruits were the foods negatively associated with MS. CONCLUSIONS: The intake of soluble fibers, particularly from whole-grain foods and fruits, may have a protective role for the presence of MS in this selected sample of patients with type 2 DM.

[The vestibulocollic reflex: assessment and characteristics of vestibular-evoked myogenic potentials analysed by age groups]. / Reflejo vestibulocervical. Valoracion y caracteristicas de los potenciales vestibulares miogenicos evocados analizados por tramos de edad.

INTRODUCTION: Obtaining vestibular-evoked myogenic potentials (VEMP) by means of the vestibulocollic reflex is a readily available technique that provides an image of vestibular functioning and is useful for evaluating the pathologies that involve compromise of the anatomical pathway of the reflex. Although normal patterns do exist, responses vary at different ages. AIM: To obtain reference values of the vestibulocollic reflex according to different age groups. SUBJECTS AND METHODS: We studied 40 volunteers with no symptoms of auditory or vestibular compromise. Each ear was stimulated separately by a series of clicks (sounds lasting 0.1 s; 3 pps; intensities of 100 dB nHL and 85 dB nHL) and recordings were made in the sternocleidomastoid muscles by means of surface electrodes as patients who were lying on their backs contracted these muscles as they lifted their heads. We studied the latency of the initial p13-n23 positive-negative potential and the peak-to-peak amplitude. The existence of later n34-p44 potentials was evaluated. RESULTS: No statistically significant differences were found between genders or between the two ears. We did not find any differences between the latencies of the waves according to the intensity of the stimulus, but there is a relationship between the amplitude of the p13-n23 potential and the intensity of the stimulus. The latencies of the responses in children under 10 years of age differ from those of the other groups, but no differences were found among those over the age of 11. CONCLUSIONS: The VEMP display steady and easily identifiable latencies. We obtained different reference values for latency in children under the age of 10 and those over 11 years old. The amplitude decreases with the intensity of the stimulus.

Reflejo vestibulocervical. Valoración y características de los potenciales vestibulares miogénicos evocados analizados por tramos de edad / The vestibulocollic reflex. assessment and characteristics of vestibular-evoked myogenic potentials analysed by age groups

Introducción. La obtención de potenciales vestibulares miogénicos evocados (PVME) mediante la realización del reflejo vestibulocervical es una técnica de fácil obtención que da una imagen de la función vestibular y es útil para valorar las patologías que impliquen afectación de la vía anatómica del reflejo. Aunque existen patrones normales, a distintas edades podemos encontrar variaciones en las respuestas. Objetivo. Obtener valores de referencia por tramos de edad del reflejo vestibulocervical. Sujetos y métodos. Estudiamos a 40 voluntarios sin síntomas de afectación auditiva o vestibular. Se estimula mediante clics (sonidos de 0,1 s de duración; 3 pps; intensidades de 100 dB nHL y 85 dB nHL), cada oído por separado, y se registra en los músculos esternocleidomastoideos mediante electrodos de superficie mientras el paciente los contrae al alzar la cabeza desde el decúbito supino. Hemos estudiado la latencia del potencial positivo-negativo inicial p13-n23 y la amplitud pico-pico. Se valora la existencia de potenciales más tardíos n34-p44. Resultados. No encontramos diferencias estadísticamente significativas entre géneros ni entre ambos oídos. No observamos diferencias entre latencias de las ondas en función de la intensidad del estímulo, y existe una relación entre la amplitud del potencial p13-n23 y la intensidad del estímulo. Las latencias de las respuestas en menores de 10 años difieren del resto de grupos, pero no existen diferencias en los mayores de 11 años. Conclusiones. Los PVME muestran unas latencias estables y fácilmente identificables. Obtenemos los valores de referencia de latencia diferentes para menores de 10 años y para los mayores de 11. La amplitud decrece en función de la intensidad del estímulo

Introduction. Obtaining vestibular-evoked myogenic potentials (VEMP) by means of the vestibulocollic reflex is a readily available technique that provides an image of vestibular functioning and is useful for evaluating the pathologies that involve compromise of the anatomical pathway of the reflex. Although normal patterns do exist, responses vary at different ages. Aim. To obtain reference values of the vestibulocollic reflex according to different age groups. Subjects and methods. We studied 40 volunteers with no symptoms of auditory or vestibular compromise. Each ear was stimulated separately by a series of clicks (sounds lasting 0.1 s; 3 pps; intensities of 100 dB nHL and 85 dB nHL) and recordings were made in the sternocleidomastoid muscles by means of surface electrodes as patients who were lying on their backs contracted these muscles as they lifted their heads. We studied the latency of the initial p13-n23 positive-negative potential and the peak-to-peak amplitude. The existence of later n34-p44 potentials was evaluated. Results. No statistically significant differences were found between genders or between the two ears. We did not find any differences between the latencies of the waves according to the intensity of the stimulus, but there is a relationship between the amplitude of the p13-n23 potential and the intensity of the stimulus. The latencies of the responses in children under 10 years of age differ from those of the other groups, but no differences were found among those over the age of 11. Conclusions. The VEMP display steady and easily identifiable latencies. We obtained different reference values for latency in children under the age of 10 and those over 11 years old. The amplitude decreases with the intensity of the stimulus