Miracle-dz/UniFAR-FTUs huggingface dataset:
Genetic variation at NNRTI resistance-associated positions in patients infected with HIV-1 subtype C

Objective: Genetic differences between subtypes of HIV-1, even when not associated with key resistance mutations, are known to affect baseline susceptibility to specific antiretroviral drugs and resistance-development pathways. We studied the prevalence and patterns of non-nucleoside reverse transcriptase inhibitor (NNRTI)-associated mutations in HIV-1 subtype C-infected patients. Method: We analysed the genetic variation at sites associated with NNRTI and nucleoside reverse transcriptase inhibitor resistance in subtype C- versus B-infected patients, both drug-naive and -experienced. We extended the comparison to subtype B records from the Stanford database. Results: A total of 150 subtype B and 341 subtype C-infected patients were studied. No significant differences were found in treatment and clinical parameters between the groups. In NNRTI-naive patients, changes in NNRTI positions were present in 9.3% of subtype B- versus 33.1% of subtype C-infected patients (P < 0.001). Differences were seen in both drug-naive (subtype B, 10.0% versus subtype C, 50.1%; P < 0.021) and drug-experienced NNRTI-naive patients (subtype B, 9.0% versus subtype C, 23.8%; P < 0.001). In NNRTI experienced patients, the number of A98G/S changes was significantly higher in subtype C patients treated with either efavirenz or nevirapine (P < 0.0001), and V106M was higher in efavirenz-treated subtype C-infected patients (P < 0.0001). The average mutation rates were 1.26 and 1.67 per patient for subtypes B and C, respectively (P = 0.036). The frequency of nucleoside associated mutations, but not M184V, in treated patients was significantly higher in subgroup B-infected patients (P = 0.028). Conclusion: Collectively, these data indicate that genetic variation at NNRTI resistance-associated positions such as V106M and A98S is substantially greater in subtype C-infected patients than in subtype B-infected patients. The natural structure of each subtype probably affects the frequency and pattern of drug resistance mutations selected under treatment.
Mitochondrial Reactive Oxygen Species Are Required for Hypothalamic Glucose Sensing

The physiological signaling mechanisms that link glucose sensing to the electrical activity in metabolism-regulating hypothalamus are still controversial. Although ATP production was considered the main metabolic signal, recent studies show that the glucose-stimulated signaling in neurons is not totally dependent on this production. Here, we examined whether mitochondrial reactive oxygen species (mROS), which are physiologically generated depending on glucose metabolism, may act as physiological sensors to monitor the glucose-sensing response. Transient increase from 5 to 20 mmol/l glucose stimulates reactive oxygen species (ROS) generation on hypothalamic slices ex vivo, which is reversed by adding antioxidants, suggesting that hypothalamic cells generate ROS to rapidly increase glucose level. Furthermore, in vivo, data demonstrate that both the glucose-induced increased neuronal activity in arcuate nucleus and the subsequent nervous-mediated insulin release might be mimicked by the mitochondrial complex blockers antimycin and rotenone, which generate mROS. Adding antioxidants such as trolox and catalase or the uncoupler carbonyl cyanide m-chlorophenylhydrazone in order to lower mROS during glucose stimulation completely reverses both parameters. In conclusion, the results presented here clearly show that the brain glucose-sensing mechanism involved mROS signaling. We propose that this mROS production plays a key role in brain metabolic signaling.
Occurrence and characterization of carbapenemase-producing Enterobacteriaceae: report from the SENTRY Antimicrobial Surveillance Program (2000-2004).

Emergence and dissemination of Enterobacteriaceae isolates harboring carbapenemases in various geographic regions represents a significant threat to the management of nosocomial infections. Enterobacteriaceae isolates from the SENTRY Antimicrobial Surveillance Program (2000-2004) demonstrating decreased susceptibility to imipenem and meropenem (minimum inhibitory concentration [MIC], > or =2 mg/L) were evaluated for the production of metallo-beta-lactamases and serine carbapenemases using disk approximation and polymerase chain reaction (PCR) tests. Carbapenemase-producing strains were epidemiologically typed by automated riboprinting and pulsed-field gel electrophoresis (PFGE) to establish clonality. Among 37,557 Enterobacteriaceae (5 genus groups) evaluated, 119 (0.32%) had increased carbapenem MIC values, and a carbapenemase was identified in 51 (42.9%) of these strains. KPC-2 and KPC-3 were the most frequently occurring carbapenemases (24 isolates, 20.2%) in the United States and were detected in Klebsiella spp, Citrobacter spp. , Enterobacter spp. , and Serratia marcescens strains isolated in New York, Arkansas, and Virginia. SME-2-producing S. marcescens were isolated in the New York City area, Texas, and Ohio, while NMC-A was found in one E. cloacae strain from New York. In contrast, metallo-beta-lactamases were prevalent in Europe. IMP-1-producing E. cloacae (11 isolates) were detected in Turkey, while VIM-1-producing strains were found in Italy (Enterobacter spp.) and Greece (Klebsiella pneumoniae). Clonal dissemination of carbapenemase-producing strains was observed in several medical centers on both continents. The occurrence of carbapenemases in various Enterobacteriaceae remains rare but appears to be spreading geographically (not in Latin America), mainly with metallo-beta-lactamases being found in Mediterranean Europe and KPC enzymes in the New York City area.
Potential Roles of Peripheral Dopamine in Tumor Immunity

Recent years, immunotherapy has turned out to be a promising strategy against tumors. Peripheral dopamine (DA) has important roles in immune system among tumor patients. Accumulated reports demonstrate variable expression and distribution of DA receptors (DRs) in diverse immune cells. Interestingly, peripheral DA also involves in tumor progression and it exerts anticancer effects on immunomodulation, which includes inflammasomes in cancer, function of immune effector cells, such as T lymphocytes, myeloid-derived suppressor cells (MDSCs), tumor-associated macrophages (TAMs) and natural killer (NK) cells. Given the specific immunologic status, DA medication may be a valuable candidate in pancreatic cancer treatment. The major purpose of this review is to discuss the novel potential interactions between peripheral dopamine and tumor immunity.
Analysis of Local Cytokine Gene Expression in Patients With Allergic Rhinitis Treated With CO2 Laser Surgery

Objectives/Hypothesis Laser surgery of the inferior turbinates has become a popular surgical treatment for patients with allergic rhinitis, particularly for those who have persistent nasal obstruction and do not respond well to pharmacological therapy. The aim of this study was to investigate the effects of the laser surgery on local cytokine gene expression at the mucosal surface in relation to the improvement of nasal symptoms.
Granger Predictability of Oil Prices after the Great Recession

Real oil prices surged from 2009 through 2014, comparable to the 1970’s oil shock period. Standard explanations based on monopoly markup fall short since inflation remained low after 2009. This paper contributes strong evidence of Granger (1969) predictability of nominal factors to oil prices, using one adjustment to monetary aggregates. This adjustment is the subtraction from the monetary aggregates of the 2008-2009 Federal Reserve borrowing of reserves from other Central Banks (Swaps), made after US reserves turned negative. This adjustment is key in that Granger predictability from standard monetary aggregates is found only with the Swaps subtracted.
Pharmacological indices and pulmonary distribution of rifampicin after repeated oral administration in healthy foals

BACKGROUND The treatment of equine lung infections by Rhodococcus equi with rifampicin is empirically based because pharmacokinetic/pharmacodynamic (PK/PD) indices and pivotal clinical outcome data are not available. OBJECTIVES To evaluate the pharmacokinetics and pulmonary distribution of rifampicin into epithelial lining fluid (ELF) and bronchoalveolar lavage cells (BALC) to predict antimicrobial activity in the lung using PK/PD indices. STUDY DESIGN Controlled, randomised, two-period, crossover, repeated-dose study with an initial arm to measure disposition after i.v. administration of rifampicin. METHODS Pharmacokinetics and lung distribution were evaluated in six healthy foals treated with 10 mg/kg bwt rifampicin i.v. (initial arm) and with repeated oral doses of rifampicin at 10 mg/kg bwt and 20 mg/kg bwt once per day for 10 days (crossover arms). ELF and BALC were sampled by bronchoalveolar lavage 24 h after the last oral dosing. Rifampicin and 25-O-desacetyl rifampicin were quantified using liquid chromatography tandem-mass spectrometry. Enzyme induction by rifampicin was confirmed by evaluation of plasma 4β-OH-cholesterol:cholesterol ratios. RESULTS The distribution volume of rifampicin administered i.v. was ~0.85 L/kg. Terminal elimination half-life was ~11 h. Orally given rifampicin was slowly absorbed (Tmax , range: 2.5-8.0 h) and eliminated with apparent half-lives of ~6-8 h. Trough concentrations in ELF and BALC were 1.01 ± 0.20 μg/mL and 1.25 ± 0.29 μg/mL, respectively, after 10 mg/kg bwt rifampicin and 2.71 ± 1.25 μg/mL and 3.09 ± 1.63 μg/mL, respectively, after 20 mg/kg bwt rifampicin. The average ratios of area under the plasma concentration time curve during an administration interval of 24 h (AUC0-24 h ) to minimum inhibitory concentration (MIC) were 145 and 322 h, respectively, for less susceptible strains of R. equi (MIC90 : 0.5 μg/mL). MAIN LIMITATIONS The clearance and bioavailability of rifampicin after repeated oral dosing were not evaluated. CONCLUSIONS Treatment with rifampicin at 10 mg/kg bwt administered once per day is suitable to generate drug concentrations above the MIC90 in the ELF and BALC of foals. Future clinical studies with rifampicin in combination with macrolide antibiotics with low drug interaction potential are required to translate the PK/PD indices into protocols for the treatment of R. equi lung infections.
The sleeves of Dollarization’s straitjacket over Ecuador

IntroductionEcuador's inflation is not converging towards that of the United States; that the drop in Ecuador's inflation is due to the domino effect of the fall in interest rates on public debt, that is, the "price" of money for using a hard currency, which in turn is due to the dollarization which is a commitment tool that guarantees that the country will not devalue. Objective tries to demonstrate that this elimination of the senora has direct repercussions on all aspects of the economy of the country, and that when eliminated requires these variables to be reorganized to fill such a gap. Materials and methods will summarize the ideas of Solow's economic convergence model, followed by the market model of human capital and endogenous growth through the technology proposed by Romer Result. This re-organization of the variables of the Ecuadorian economic model will result in Ecuador's economic growth rate is a reflection. Discussion Dollarization creates the necessary conditions for projects aimed at improving industries Conclusions This study also shows that social mobility in Ecuador will almost stagnate.
Warm Temperatures Activate TRPV4 in Mouse 308 Keratinocytes*

Mammalian survival requires constant monitoring of environmental and body temperature. Recently, several members of the transient receptor potential vanilloid (TRPV) subfamily of ion channels have been identified that can be gated by increases in temperature into the warm (TRPV3 and TRPV4) or painfully hot (TRPV1 and TRPV2) range. In rodents, TRPV3 and TRPV4 proteins have not been detected in sensory neurons but are highly expressed in skin epidermal keratinocytes. Here, we show that in response to warm temperatures (>32 °C), the mouse 308 keratinocyte cell line exhibits nonselective transmembrane cationic currents and Ca2+ influx. Both TRPV3 and TRPV4 are expressed in 308 cells. However, the warmth-evoked responses we observe most closely resemble those mediated by recombinant TRPV4 on the basis of their electrophysiological properties and sensitivity to osmolarity and the phorbol ester, 4α-phorbol-12,13-didecanoate. Together, these data support the notion that keratinocytes are capable of detecting modest temperature elevations, strongly suggest that TRPV4 participates in these responses, and define a system for the cell biological analysis of warmth transduction.
Contribution of type III interferons to antiviral immunity: location, location, location

Type I interferons (IFN-α/β) and the more recently identified type III IFNs (IFN-λ) function as the first line of defense against virus infection and regulate the development of both innate and adaptive immune responses. Type III IFNs were originally identified as a novel ligand-receptor system acting in parallel with type I IFNs, but subsequent studies have provided increasing evidence for distinct roles for each IFN family. In addition to their compartmentalized antiviral actions, these two systems appear to have multiple levels of cross-regulation and act coordinately to achieve effective antimicrobial protection with minimal collateral damage to the host.
N‐linked glycosylation of the liver cancer biomarker GP73

The association between elevated circulating levels of GP73 (and fucosylated GP73 in particular) and hepatocellular carcinoma suggests that a thorough analysis of the extent of GP73 glycosylation is warranted. Detailed analysis of the glycosylation patterns of such low abundance proteins are hampered by technical difficulties. Using conventional lectin affinity chromatography, we have established that three quarters of the GP73 secreted from a cell line derived from HCC is fucosylated. Using mass spectrometry, we have established that at least two of three potential sites of N‐linked glycosylation are occupied on most molecules of GP73 secreted from cultured hepatoma cells. Furthermore, the oligosaccharides added to recombinant GP73 resemble those present in the bulk of secreted protein, mostly bi‐antennary with core fucose, with a smaller fraction of tri‐ and tetra‐antennary structures. The frequency of fucosylation observed on the recombinant protein agrees well with the pattern of lectin binding of the endogenous secreted protein. Finally, we have developed a method to interrogate the glycans added to either the near full length protein or at a particular sequon, providing proof of concept that a small peptide embedded in a heterologous context can preserve both fucosylation and a high level of branching of oligosaccharides added. J. Cell. Biochem. 104: 136–149, 2008. © 2007 Wiley‐Liss, Inc.
Gender Quotas or Girls’ Networks? Evidence from an Italian Research Selection

This article investigates the role of the gender composition of selection committees and connections in promoting women in research. Exploiting a newly collected data set on research recruitment processes to entry-level positions in a leading Italian research centre operating mainly in the hard sciences, the study finds that bias against women manifests itself at non-tenured entry level and is attenuated by the presence of a woman on the selection committee. However, the most important predictor for recruitment in the study is previous connections with the research centre, a mechanism which, due to the lower density of network links with the institute among female candidates, operates as a selection device discriminating against women. The results suggest that the gender of the committee members, network structure and type of recruitment must all be considered in approaching recruitment policy.
Novel genetic and neuropathological insights in neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP)

Introduction: Neurogenic muscle weakness, ataxia, and retinitis pigmentosa (NARP) is caused by m.8993T>G/C mutations in the mitochondrial adenosine triphosphate synthase subunit 6 gene (MT‐ATP6). Traditionally, heteroplasmy levels between 70% and 90% lead to NARP, and >90% result in Leigh syndrome. Methods: In this study we report a 30‐year‐old man with NARP and m.8993T>G in MT‐ATP6. Results: Although the patient carried the mutation in homoplasmic state in blood with similarly high levels in urine (94%) and buccal swab (92%), he presented with NARP and not the expected, more severe Leigh phenotype. The mutation could not be detected in any of the 3 analyzed tissues of the mother, indicating a large genetic shift between mother and offspring. Nerve biopsy revealed peculiar endoneurial Schwann cell nuclear accumulations, clusters of concentrically arranged Schwann cells devoid of myelinated axons, and degenerated mitochondria. Conclusions: We emphasize the phenotypic variability of the m.8993T>G MT‐ATP6 mutation and the need for caution in predictive counseling in such patients. Muscle Nerve 54: 328–333, 2016
Cross-modal Processing in the Occipito-temporal Cortex: A TMS Study of the Müller-Lyer Illusion

The Müller-Lyer illusion occurs both in vision and in touch, and transfers cross-modally from vision to haptics [Mancini, F. , Bricolo, E. , & Vallar, G. Multisensory integration in the Müller-Lyer illusion: From vision to haptics. Quarterly Journal of Experimental Psychology, 63, 818–830, 2010]. Recent evidence suggests that the neural underpinnings of the Müller-Lyer illusion in the visual modality involve the bilateral lateral occipital complex (LOC) and right superior parietal cortex (SPC). Conversely, the neural correlates of the haptic and cross-modal illusions have never been investigated previously. Here we used repetitive TMS (rTMS) to address the causal role of the regions activated by the visual illusion in the generation of the visual, haptic, and cross-modal visuo-haptic illusory effects, investigating putative modality-specific versus cross-modal underlying processes. rTMS was administered to the right and the left hemisphere, over occipito-temporal cortex or SPC. rTMS over left and right occipito-temporal cortex impaired both unisensory (visual, haptic) and cross-modal processing of the illusion in a similar fashion. Conversely, rTMS interference over left and right SPC did not affect the illusion in any modality. These results demonstrate the causal involvement of bilateral occipito-temporal cortex in the representation of the visual, haptic, and cross-modal Müller-Lyer illusion, in favor of the hypothesis of shared underlying processes. This indicates that occipito-temporal cortex plays a cross-modal role in perception both of illusory and nonillusory shapes.
The cost-effectiveness of four treatments for marijuana dependence.

AIM To analyze data from a randomized clinical trial to determine the cost-effectiveness of using contingency management (CM) and motivational/skills building therapy (motivational enhancement therapy/cognitive-behavioral therapy: MET/CBT) to treat young adults with marijuana dependence. PARTICIPANTS, DESIGN AND MEASUREMENTS: A total of 136 marijuana-dependent young adults, all referred by the criminal justice system, were randomized to one of four treatment conditions: MET/CBT with CM, MET/CBT without CM, drug counseling (DC) with CM and DC without CM. Patient outcome measures include the longest duration of confirmed marijuana abstinence (LDA) during treatment and the total number of marijuana-free urine specimens provided during treatment. Costs were collected retrospectively from the provider and include the costs of therapy, patient drug testing, and those associated with the incentives component (value of vouchers, time to administer the voucher system). SETTING Out-patient substance abuse clinic in New Haven, Connecticut, USA. FINDINGS Which treatment is the most cost-effective depends on the threshold values of an additional week of LDA or an additional marijuana-free urine specimen. For example, the most effective treatment, MET/CBT with CM, was also the most cost-effective treatment at the highest threshold values, while the least effective treatment, DC, was the most cost-effective at the lowest values. Because consensus threshold values for these patient outcomes do not exist, results are presented showing the ranges of values over which each treatment would be considered cost-effective compared to the others. Acceptability curves are presented to show the decision uncertainty associated with these ranges. The results are shown to be robust to (i) sensitivity analyses on several key cost parameters and (ii) patient outcomes measured during the 6-month follow-up period. CONCLUSIONS This study uses incremental cost-effectiveness ratios and acceptability curves to shed light on the relative cost-effectiveness of four interventions for treating young adults with marijuana dependence. Given the relatively small and specialized nature of our study sample, and the fact that we examined a CM procedure with a single reinforcement schedule, additional studies are warranted to determine the reliability and generalizability of our results both to alternative marijuana-using populations and to CM procedures with alternative incentive parameters. Nevertheless, the relative durability of effects of MET/CBT compared to DC through the 6-month follow-up, and its cost-effectiveness over a comparatively wide range of threshold values, underscores the promise of this approach.
Agilité et conception de filière : le cas de la montre SWATCH

Lors du lancement de nouveaux produits, les entreprises innovantes doivent anticiper l'organisation de la filiere, supportant la fabrication du produit et que de fait, elles doivent aussi redefinir leur role au sein de cette derniere pour rester competitive. Une reflexion doit donc etre menee des la conception du nouveau produit afin d'anticiper les changements organisationnels, technologiques ou strategiques occasionnes. Une filiere « dite » agile facilite l'integration d'un nouveau produit en limitant les risques induits par ces differents changements. Dans cet article, nous montrerons qu'anticiper la conception de la filiere, au plus tot dans le processus de developpement du nouveau produit, permet de mettre en oeuvre les strategies les plus efficaces pour la rendre agile et donc plus apte a supporter les aleas et les incertitudes decoulant de l'innovation. Pour illustrer nos propos, le cas emblematique de la Swatch est etudie.