Miracle-dz/UniFAR-FTUs huggingface dataset:
Streptococcus pneumoniae Response to Repeated Moxifloxacin or Levofloxacin Exposure in a Rabbit Tissue Cage Model

ABSTRACT The role of moxifloxacin and levofloxacin pharmacokinetics (PK) in antimicrobial efficacy and in the selection of fluoroquinolone-resistant Streptococcus pneumoniae strains was investigated using the rabbit tissue cage abscess model. A rabbit tissue cage was created by insertion of sterile Wiffle balls in the dorsal cervical area. Animals orally received a range of moxifloxacin or levofloxacin doses that simulate human PK for 7 days 48 h after the Wiffle balls were inoculated with fluoroquinolone-sensitiveS. pneumoniae (107 CFU). Abscess fluid was collected on a daily basis over 14 days to measure bacterial density and MICs. Moxifloxacin regimens produced a range of area under the concentration-time curve (AUC)/MIC ratios ranging from 9.2 to 444 and peak/MIC ratios ranging from 1.3 to 102. Levofloxacin doses produced AUC/MIC ratios of 5.1 to 85.5 and peak/MIC ratio of 0.9 to 14.8. Moxifloxacin at 6.5, 26, and 42 mg/kg reduced the bacterial log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 4.2 ± 2.2 (20%), 5.8 ± 0.4 (100%), and 5.4 ± 0.4 (100%), respectively, over the dosing period. Levofloxacin at 5.5, 22, and 32 mg/kg reduced the log CFU per milliliter in abscess fluid (percentage of that in a sterile animal) by 2.8 ± 0.7 (20%), 5.1 ± 1.3 (80%), and 4.6 ± 1.3 (60%), respectively. Moxifloxacin has a greater bactericidal rate as determined by regression of log CFU versus time data. The AUC/MIC and peak/MIC ratios correlated with the efficacy of both drugs (P< 0.05). Resistance to either drug did not develop with any of the doses as assessed by a change in the MIC. In conclusion, data derived from this study show that moxifloxacin and levofloxacin exhibit rapid bactericidal activity against S. pneumoniae in vivo, and moxifloxacin exhibits enhanced bactericidal activity compared to levofloxacin, with AUC/MIC and peak/MIC ratios correlated with antimicrobial efficacy for both drugs. The development of fluoroquinolone-resistant S. pneumoniae was not observed with either drug in this model.
Sequential Retraction Segregates SGN Processes during Target Selection in the Cochlea

A hallmark of the nervous system is the presence of precise patterns of connections between different types of neurons. Many mechanisms can be used to establish specificity, including homophilic adhesion and synaptic refinement, but the range of strategies used across the nervous system remains unclear. To broaden the understanding of how neurons find their targets, we studied the developing murine cochlea, where two classes of spiral ganglion neurons (SGNs), type I and type II, navigate together to the sensory epithelium and then diverge to contact inner hair cells (IHCs) or outer hair cells (OHCs), respectively. Neurons with type I and type II morphologies are apparent before birth, suggesting that target selection might be accomplished by excluding type I processes from the OHC region. However, because type I processes appear to overshoot into type II territory postnatally, specificity may also depend on elimination of inappropriate synapses. To resolve these differences, we analyzed the morphology and dynamic behaviors of individual fibers and their branches as they interact with potential partners. We found that SGN processes continue to be segregated anatomically in the postnatal cochlea. Although type I-like fibers branched locally, few branches contacted OHCs, arguing against synaptic elimination. Instead, time-lapse imaging studies suggest a prominent role for retraction, first positioning processes to the appropriate region and then corralling branches during a subsequent period of exuberant growth and refinement. Thus, sequential stages of retraction can help to achieve target specificity, adding to the list of mechanisms available for sculpting neural circuits. SIGNIFICANCE STATEMENT During development, different types of neurons must form connections with specific synaptic targets, thereby creating the precise wiring diagram necessary for adult function. Although studies have revealed multiple mechanisms for target selection, we still know little about how different strategies are used to produce each circuit's unique pattern of connectivity. Here we combined neurite-tracing and time-lapse imaging to define the events that lead to the simple binary wiring specificity of the cochlea. A better understanding of how the cochlea is innervated will broaden our knowledge of target selection across the nervous system, offer new insights into the developmental origins of deafness, and guide efforts to restore connectivity in the damaged cochlea.
p38 Mitogen‐activated protein kinase‐dependent regulation of SRC‐3 and involvement in retinoic acid receptor α signaling in embryonic cortical neurons

Appropriate retinoic acid (RA) signaling is essential in the development of the central nervous system (CNS). Previous studies have shown that RA activates p38 mitogen‐activated protein kinase (MAPK) and steroid receptor coactivator (SRC)‐3 in tumor cells in vitro. It is unknown whether the activation of p38 MAPK and SRC‐3 is involved in RA‐mediated CNS development. The current study investigated a possible role for p38 MAPK in the regulation of (SRC)‐3 phosphorylation/degradation and in retinoic acid receptor (RAR)α signaling in mouse fetal cortical neurons treated with all‐trans retinoic acid (ATRA). Results showed that ATRA treatment rapidly activated p38 MAPK, which in turn resulted in phosphorylation with subsequent degradation of SRC‐3. Inhibition of p38 MAPK by SB203580 blocked the phosphorylation and degradation of SRC‐3. The binding of RARα to retinoic acid responsive element (RARE) was rapidly increased in neurons following ATRA treatment. Inhibition of p38 MAPK significantly enhanced the RARα‐RARE binding activity, but had no effects on ATRA‐induced decrease of RARα. Treatment of the fetal cortical neurons with ATRA significantly increased the expression of HOXd3, a retinoid‐target gene. The increase of HOXd3 expression was augmented when p38 MAPK activity was inhibited by a specific inhibitor, SB203580. Results suggest that ATRA activates the p38 MAPK signal pathway with resultant degradation of SRC‐3, and that p38 MAPK is involved in the regulation of RARα‐mediated signaling in developing neurons. © 2009 IUBMB IUBMB Life, 61(6): 670–678, 2009
HLA-DRB association in neuromyelitis optica is different from that observed in multiple sclerosis

Until recently, neuromyelitis optica (NMO) was considered to be a sub-type of multiple sclerosis (MS), which has a strong predilection for Caucasian populations, whereas NMO is more frequent in non-Caucasian individuals. The objective of this study was to compare the HLA-DRB profile in Brazilian Mulatto patients with NMO spectrum disorders (NMOSDs) with that observed for Mulatto MS patients and healthy Mulatto controls. Twenty seven NMOSD patients (20 women), all seropositive for NMO-IgG, 29 MS patients and 28 Mulatto healthy blood donors were evaluated for HLA-DRB allele groups. HLA-DRB1*03 allele group was overrepresented in NMO patients compared with healthy controls (p = 0.0401; OR = 3.23, 95%CI: 1.07—9.82). In contrast, the HLA-DRB1*15 allele group was overrepresented in Brazilian MS patients (OR = 15.89, 95%CI: 3.51—71.85; p < 0.0001). DRB3 was overrepresented in NMO (p = 0.0064), and DRB5 overrepresented in MS patients (p = 0.0001). The low frequency of HLA-DRB1*15 alleles was associated with the presence of long and central cord lesions at magnetic resonance. In addition, DRB1*15 alleles were associated with the fulfillment of the Barkhof criteria. In conclusion, these results indicate that the DRB profile of NMO patients is different from that observed for MS patients, further corroborating the distinction between NMO and MS.
A Worst-Case Robust Beamforming Design for Multi-Antenna AF Relaying

In this paper, we consider relay precoder optimization for a multi-antenna amplify-and-forward (AF) relaying system using imperfect channel state information (CSI) with either additive or multiplicative deterministic uncertainties. Adopting worst-case robustness, we aim to maximize the worst-case received signal-to-noise ratio (SNR) at the destination subject to the power constraint at the relay. Despite the non-convexity of the design problem, we obtain a closed-form solution and discover that beamforming along the nominal channel direction achieves the best performance with channel uncertainties. Based on the optimal solution, we further analyze the impact of imperfect CSI on the performance of the robust multi-antenna AF relaying system and carry out simulations to verify our analysis.
Transcriptome Analysis of Lactococcus lactis in Coculture with Saccharomyces cerevisiae

ABSTRACT The study of microbial interactions in mixed cultures remains an important conceptual and methodological challenge for which transcriptome analysis could prove to be the essential method for improving our understanding. However, the use of whole-genome DNA chips is often restricted to the pure culture of the species for which the chips were designed. In this study, massive cross-hybridization was observed between the foreign cDNA and the specific Lactococcus lactis DNA chip. A very simple method is proposed to considerably decrease this nonspecific hybridization, consisting of adding the microbial partner's DNA. A correlation was established between the resulting cross-hybridization and the phylogenetic distance between the microbial partners. The response of L. lactis to the presence of Saccharomyces cerevisiae was analyzed during the exponential growth phase in fermentors under defined growth conditions. Although no differences between growth kinetics were observed for the pure and the mixed cultures of L. lactis, the mRNA levels of 158 genes were significantly modified. More particularly, a strong reorientation of pyrimidine metabolism was observed when L. lactis was grown in mixed cultures. These changes in transcript abundance were demonstrated to be regulated by the ethanol produced by the yeast and were confirmed by an independent method (quantitative reverse transcription-PCR).
Honey‐Making Bee Colony Abundance and Predation by Apes and Humans in a Uganda Forest Reserve 1

Honey‐making bee colonies in Bwindi Impenetrable National Park were investigated with Batwa Pygmies locating 228 nests of Apis and five stingless bees (Meliponini). The relative importance of predation, food supply, nesting site, and elevation affecting abundance were studied for meliponines in particular. Nest predation and overall nest abundance had no correlation with elevation along a 1400 m gradient, nor did flowering phenology or pollen collection. Many suitable, large trees were unoccupied by bee nests. In 174 ha of forest plots, 2 Meliponula lendliana, 13 M. nebulata, 16 M. ferruginea, 16 M. bocandei, and 20 Apis mellifera adansonii nests occurred, suggesting a habitat‐wide density of 39 nests/km2. Compared to other studies, Ugandan Meliponini were uncommon (0.27 colonies/ha, tropical mean = 1.9/ha), while Apis mellifera was numerous (0.12 nests/ha, tropical mean = 0.06/ha), despite park policy allowing humans to exploit Apis. Meliponine colony mortality from predators averaged 12 percent/yr and those near ground were most affected. Tool‐using humans and chimpanzees caused 82 percent of stingless bee nest predation. Selective factors affecting nest heights and habit may include auditory hunting by predators for buzzing bees, and indirect mutualists such as termites that leave potential nesting cavities. Mobility and free‐nesting by honey bee colonies should enable rapid community recovery after mortality, especially in parks where human honey hunting is frequent, compared to sedentary and nest‐site‐bound Meliponini.
Diffusion of Gas from a Liquid into an Expanding Bubble

The growth of a bubble within a volume of isothermal viscous liquid containing uniformly distributed dissolved gas is considered. The problem of characterizing this growth-by-mass-transfer is reduced fo an integro-differential equation for the bubble radius as a function of time, and a computer solution is obtained. The initial and final stages of growth are treated analytically.
Hydrogen sulfide improves neutrophil migration and survival in sepsis via K+ATP channel activation.

RATIONALE Recovering the neutrophil migration to the infectious focus improves survival in severe sepsis. Recently, we demonstrated that the cystathionine gamma-lyase (CSE)/hydrogen sulfide (H(2)S) pathway increased neutrophil recruitment to inflammatory focus during sterile inflammation. OBJECTIVES To evaluate if H(2)S administration increases neutrophil migration to infectious focus and survival of mice. METHODS Sepsis was induced by cecal ligation and puncture (CLP). MEASUREMENTS AND MAIN RESULTS The pretreatments of mice with H(2)S donors (NaHS or Lawesson's reagent) improved leukocyte rolling/adhesion in the mesenteric microcirculation as well as neutrophil migration. Consequently, bacteremia levels were reduced, hypotension and lung lesions were prevented, and the survival rate increased from approximately 13% to approximately 80%. Even when treatment was delayed (6 h after CLP), a highly significant reduction in mortality compared with untreated mice was observed. Moreover, H(2)S pretreatment prevented the down-regulation of CXCR2 and l-selectin and the up-regulation of CD11b and G protein-coupled receptor kinase 2 in neutrophils during sepsis. H(2)S also prevented the reduction of intercellular adhesion molecule-1 expression in the endothelium of the mesenteric microcirculation in severe sepsis. Confirming the critical role of H(2)S on sepsis outcome, pretreatment with dl-propargylglycine (a CSE inhibitor) inhibited neutrophil migration to the infectious focus, enhanced lung lesions, and induced high mortality in mice subjected to nonsevere sepsis (from 0 to approximately 80%). The beneficial effects of H(2)S were blocked by glibenclamide (a ATP-dependent K(+) channel blocker). CONCLUSIONS These results showed that H(2)S restores neutrophil migration to the infectious focus and improves survival outcome in severe sepsis by an ATP-dependent K(+) channel-dependent mechanism.
Relationship Between Age and Diagnosis on Volumetric and Linear Velopharyngeal Measures in the Cleft and Noncleft Populations

AbstractThe purpose of this study was to create a 3D volumetric segmentation from magnetic resonance imaging (MRI) of the nasopharyngeal space and adenoid tissue and to examine the relationship between nasopharyngeal volume (NPV), adenoid volume, and linear measures of the velopharyngeal structures, pharynx, and vocal tract in children with and without cleft palate. A total of 24 participants including 18 typically developing children (4–8 years of age) and 6 children (4–8 years of age) with varying degrees of cleft palate were imaged using MRI. Linear and volumetric variables varied significantly based on age. Overall, NPV demonstrates a modest increase with age. Nasopharyngeal volume was positively correlated with age (P = 0.000), oronasopharyngeal volume (P = 0.000), velar length (P = 0.018), and velar thickness (P = 0.046). These variables tend to increase together. Differences in NPV between groups (bilateral cleft lip and palate, submucous cleft lip and palate, unilateral cleft lip and palate [UCLP], and noncleft) were statistically significant (P = 0.007). Participants with bilateral cleft lip and palate demonstrated greater NPVs than those with UCLP and submucous cleft palate.
Trends in hepatitis C‐related mortality in Switzerland

In order to accurately assess the burden of hepatitis C (HCV) and develop effective interventions, we must understand the magnitude and trends of mortality related to the disease. In the United States, HCV‐related mortality is continuously increasing. We have no comparable data for Switzerland and other European countries, although a modelling study predicted a similar increase. We analysed time trends (1 January 1995‐31 December 2014) in HCV‐specific mortality rates in the Swiss general population using the death registry of the Swiss Federal Statistical Office (SFSO). We compared HCV‐related mortality to HIV‐related and hepatitis B (HBV)‐related mortality. To determine potential under‐reporting in HCV‐related mortality, we probabilistically linked the SFSO data to persons who died in the Swiss Hepatitis C Cohort Study (SCCS). SFSO data showed that HCV‐related mortality more than doubled between 1995 and 2003, but has since stabilized at ~2.5/100 000 person‐years. Since 2000, HCV‐related mortality has been higher than HIV‐related mortality and was about fivefold higher in 2014. HBV‐related mortality remained low at ~0.5/100 000 person‐years. Of 4556 persons in the SCCS, 421 have died and 86.2% could be linked to the death registry. According to the SCCS, 133 deaths were HCV‐related. HCV was not mentioned on the SFSO death certificate of 45% of these (n = 60/133). In conclusion, HCV‐related mortality remained constant, possibly because quality of care was high, or because of under‐reporting or because mortality has not yet increased. However, HCV‐related mortality is now much higher than HIV‐ and HBV‐related mortality, and under‐reporting was common.
A case‐control study of multiple sclerosis

We conducted a study of 145 persons with multiple sclerosis who had been identified in a 1970 survey and 145 friend controls, to investigate whether the development of MS was associated with exposure to uncommon viruses or an older age at infection with 1 or more common viruses. The most striking finding was a strong positive association for history of infectious mononucleosis (IM), suggesting older age at exposure to Epstein-Barr virus, the most common etiologic agent of IM. We also found significant positive associations for number of different domiciles before adulthood and for visits outside the United States; both would be compatible with an increased likelihood among cases of exposures to uncommon viruses or to multiple strains of a common agent. Cases were younger at menarche, increasing the probability of viral exposure after puberty.
Helicobacter pylori: the African enigma.

Data on Helicobacter pylori infection in Africa are at odds in several aspects with those published in the west. Gastric H pyloni infection is common, almost ubiquitous in Africa, but the pattern of infection, age of acquisition, environmental, dietary, and genetic influences are different from those in the west. These differences alter the pathological role and clinical relevance of the organism in Africa where, apart from gastritis, there is no established correlation between H pyloni infection and upper gastrointestinal disease.
Molecular Cloning and Biochemical Characterization of L-N-Carbamoylase from Sinorhizobium meliloti CECT4114

An N-carbamoyl-L-amino acid amidohydrolase (L-N-carbamoylase) from Sinorhizobium meliloti CECT 4114 was cloned and expressed in Escherichia coli. The recombinant enzyme catalyzed the hydrolysis of N-carbamoyl α-amino acid to the corresponding free amino acid, and its purification has shown it to be strictly L-specific. The enzyme showed broad substrate specificity, and it is the first L-N-carbamoylase that hydrolyses N-carbamoyl-L-tryptophan as well as N-carbamoyl L-amino acids with aliphatic substituents. The apparent K<sub>m</sub> values for N-carbamoyl-L-methionine and tryptophan were very similar (0.65 ± 0.09 and 0.69 ± 0.08 mM, respectively), although the rate constant was clearly higher for the L-methionine precursor (14.46 ± 0.30 s<sup>–1</sup>) than the L-tryptophan one (0.15 ± 0.01 s<sup>–1</sup>). The enzyme also hydrolyzed N-formyl-L-methionine (k<sub>cat</sub>/K<sub>m</sub> = 7.10 ± 2.52 s<sup>–1</sup>·mM<sup>–1</sup>) and N-acetyl-L-methionine (k<sub>cat</sub>/K<sub>m</sub> = 12.16 ± 1.93 s<sup>–1</sup>·mM<sup>–1</sup>), but the rate of hydrolysis was lower than for N-carbamoyl-L-methionine (k<sub>cat</sub>/K<sub>m</sub> = 21.09 ± 2.85). This is the first L-N-carbamoylase involved in the ‘hydantoinase process’ that has hydrolyzed N-carbamoyl-L-cysteine, though less efficiently than N-carbamoyl-L-methionine. The enzyme did not hydrolyze ureidosuccinic acid or 3-ureidopropionic acid. The native form of the enzyme was a homodimer with a molecular mass of 90 kDa. The optimum conditions for the enzyme were 60°C and pH 8.0. Enzyme activity required the presence of divalent metal ions such as Ni<sup>2+</sup>, Mn<sup>2+</sup>, Co<sup>2+</sup> and Fe<sup>2+</sup>, and five amino acids putatively involved in the metal binding were found in the amino acid sequence.
Children's Attentional Skills 2 Years Post-Traumatic Brain Injury

This study examined sustained attention abilities 24 months postinjury, in 3 groups of children who had suffered a traumatic brain injury (TBI): (a) mild TBI (n = 24), (b) moderate TBI (n = 31), and (c) severe TBI (n = 14). Three manipulations of the traditional Continuous Performance Test paradigm (CPT) were employed in the study, to delineate factors that might in.uence CPT performance, including speed of processing, attentional lapses, and stimulus complexity. No significant differences were evident among the TBI groups on a measure of simple reaction time, nor on a CPT version where the interstimulus interval was lengthened. However, there was a significant difference between the mild and severe TBI groups on the most complex task, which required speed, accuracy, and decision making, suggesting that these factors underlie impaired performances previously identi.ed on the CPT in children with severe TBI. These findings have implications for the development of intervention programs for these children.
A comparison of apical root resorption after orthodontic treatment with surgical exposure and traction of maxillary impacted canines versus that without impactions.

SUMMARY BACKGROUND/OBJECTIVES Orthodontic management of maxillary canine impaction (MCI), including forced eruption, may result in significant root resorption; however, the association between MCI and orthodontically induced root resorption (OIRR) is not yet sufficiently established. The purpose of this retrospective cohort study was to comparatively evaluate the severity of OIRR of maxillary incisors in orthodontically treated patients with MCI. Additionally, impaction characteristics were associated with OIRR severity. SUBJECTS AND METHODS The sample comprised 48 patients undergoing fixed-appliance treatment-24 with unilateral/bilateral MCI and 24 matched controls without impaction. OIRR was calculated using pre- and post-operative panoramic tomograms. The orientation of eruption path, height, sector location, and follicle/tooth ratio of the impacted canine were also recorded. Mann-Whitney U-test and univariate and multivariate linear mixed models were used to test for the associations of interest. RESULTS Maxillary central left incisor underwent more OIRR in the impaction group (mean difference = 0.58mm, P = 0.04). Overall, the impaction group had 0.38mm more OIRR compared to the control (95% confidence interval, CI: 0.03, 0.74; P = 0.04). However, multivariate analysis demonstrated no difference in the amount of OIRR between impaction and non-impaction groups overall. A positive association between OIRR and initial root length was observed (95% CI: 0.08, 0.27; P < 0.001). The severity of canine impaction was not found to be a significant predictor of OIRR. LIMITATIONS This study was a retrospective study and used panoramic tomograms for OIRR measurements. CONCLUSIONS This study indicates that MCI is a weak OIRR predictor. Interpretation of the results needs caution due to the observational nature of the present study.