Design of ferrocene-dipeptide bioorganometallic conjugates to induce chirality-organized structures.
The highly ordered molecular assemblies in proteins can have a variety of functions, as observed in enzymes, receptors, and the like. Synthetic scientists are constructing bioinspired systems by harnessing the self-assembling properties of short peptides. Secondary structures such as alpha-helices, beta-sheets, and beta-turns are important in protein folding, which is mostly directed and stabilized by hydrogen bonding and the hydrophobic interactions of side chains. The design of secondary structure mimics that are composed of short peptides has attracted much attention, both for gaining fundamental insight into the factors affecting protein folding and for developing pharmacologically useful compounds, artificial receptors, asymmetric catalysts, and new materials. Ferrocenes are an organometallic scaffold with a central reverse-turn unit based on the inter-ring spacing of about 3.3 A, which is a suitable distance for hydrogen bonding between attached peptide strands. The conjugation of organometallic compounds with biomolecules such as amino acids, peptides, and DNA should provide novel systems that reflect properties of both the ferrocene and the biologically derived moieties. In this Account, we focus on recent advances in the design of ferrocene-peptide bioconjugates, which help illustrate the peptidomimetic basis for protein folding and the means of constructing highly ordered molecular assemblies. Ferrocene-peptide bioconjugates are constructed to form chirality-organized structures in both solid and solution states. The ferrocene serves as a reliable organometallic scaffold for the construction of protein secondary structures via intramolecular hydrogen bonding: the attached dipeptide strands are constrained within the appropriate dimensions. The introduction of the chiral dipeptide chains into the ferrocene scaffold induces the conformational enantiomerization of the ferrocenyl moiety; the chirality-organized structure results from intramolecular hydrogen bonding. The configuration and sequence of the amino acids are instrumental in the process. Regulation of the directionality and specificity of hydrogen bonding is a key component in the design of various molecular assemblies. Ferrocene-peptide bioconjugates also have a strong tendency to self-assemble through the contributions of available hydrogen-bonding donors in the solid state. Some ferrocene-peptide bioconjugates bearing only one dipeptide chain exhibit a helically ordered molecular assembly through a network of intermolecular (rather than intramolecular) hydrogen bonds. The propensity to form the chiral helicity appears to be controlled by the chirality of the dipeptide chains. Organization of host molecules is a useful strategy for forming artificial receptors. The conformationally regulated ferrocene-peptide bioconjugate provides the chirality-organized binding site for size-selective and chiral recognition of dicarboxylic acids through multipoint hydrogen bonds. Metal ions serve a variety of purposes in proteins, including structural stabilization for biological function. The complexation of ferrocene-peptide bioconjugates with palladium(II) compounds not only stabilizes the chirality conformational regulation but also induces conformational regulation of the dipeptide chain through complexation and intramolecular chirality organization. Construction of the chirality-organized ferrocene-peptide bioconjugates is also achieved by metal-directed assembly. These varied examples amply demonstrate the value of ferrocene-peptide bioconjugates in asserting architectural control over highly ordered molecular assemblies.


Clonal monosomy 7 in a megakaryoblastic leukemia developed on the basis of Fanconi anemia.
A 13-year-old girl with a history of Fanconi anemia developed acute myeloid leukemia of the M7 subtype with a 45,XX,-7 karyotype, which is rare in M7 subtype. Treatment protocols were set up, but she died of sepsis and osteomyelitis during induction.


Comparative sequence analysis of open reading frames 2 to 7 of the modified live vaccine virus and other North American isolates of the porcine reproductive and respiratory syndrome virus.
To elucidate changes associated with the attenuated virulence in a modified live porcine reproductive and respiratory syndrome (PRRS) vaccine (Boehringer Ingelheim Animal Health, St. Joseph, MO), derived from an American prototype ATCC virus VR-2332, nucleotide sequence of 3' genome covering open reading frames (ORFs) 2 to 7 coding regions from the vaccine virus was determined by RT-PCR with two overlapping fragments. Comparisons showed 98 base changes (94 substitutions, 3 deletions, and 1 addition) out of 3318 nucleotides between the vaccine virus and its parental virus. There were 15, 26, 17, 29, 9, and 6 base substitutions in ORFs 2, 3, 4, 5, 6, and 7, respectively, resulting in 5, 13, 8, 13, 2, and 3 amino acid (a.a.) substitutions in their deduced proteins, respectively. Most of these a.a. substitutions were also present in 17 known virulent/wild type PRRS virus isolates from North America. However, there were 1, 4, 1, and 1 unique a.a. substitutions in the vaccine virus ORFs 2, 3, 4, and 5 deduced proteins, respectively. These unique amino substitutions may be responsible for the attenuated virulence in the vaccine virus.


The effect of lunisolar tidal acceleration on stem elongation growth, nutations and leaf movements in peppermint (Mentha × piperita L.).
Orbital movement of the Moon generates a system of gravitational fields that periodically alter the gravitational force on Earth. This lunar tidal acceleration (Etide) is known to act as an external environmental factor affecting many growth and developmental phenomena in plants. Our study focused on the lunar tidal influence on stem elongation growth, nutations and leaf movements of peppermint. Plants were continuously recorded with time-lapse photography under constant illumination as well in constant illumination following 5 days of alternating dark-light cycles. Time courses of shoot movements were correlated with contemporaneous time courses of the Etide estimates. Optical microscopy and SEM were used in anatomical studies. All plant shoot movements were synchronised with changes in the lunisolar acceleration. Using a periodogram, wavelet analysis and local correlation index, a convergence was found between the rhythms of lunisolar acceleration and the rhythms of shoot growth. Also observed were cyclical changes in the direction of rotation of stem apices when gravitational dynamics were at their greatest. After contrasting dark-light cycle experiments, nutational rhythms converged to an identical phase relationship with the Etide and almost immediately their renewed movements commenced. Amplitudes of leaf movements decreased during leaf growth up to the stage when the leaf was fully developed; the periodicity of leaf movements correlated with the Etide rhythms. For the fist time, it was documented that lunisolar acceleration is an independent rhythmic environmental signal capable of influencing the dynamics of plant stem elongation. This phenomenon is synchronised with the known effects of Etide on nutations and leaf movements.


Potentiation by 4-aminopyridine of quantal acetylcholine release at the Torpedo nerve-electroplaque junction.
The effects of 4-aminopyridine (4-AP) on electrophysiological post-synaptic responses evoked by field stimulation or evoked focally using a loose patch-clamp technique, and on radiolabelled transmitter release were studied in the Torpedo electric organ. In this preparation, 4-AP had three major effects: it greatly potentiated the amount of acetylcholine (ACh) released by a nerve impulse, it prolonged the duration of the post-synaptic electroplaque current (e.c.) by several hundreds of milliseconds, and it increased the delay of responses triggered by a presynaptic action potential. Noise analysis performed at different times during the focally recorded giant response showed that it was made of a sustained release of ACh quanta. The maximum synchronous release of transmitter, expressed as the maximum number of quanta simultaneously delivered/micron2 of presynaptic membrane, was apparently not modified by 4-AP. A slightly different dose dependence was found for the effects of 4-AP on the potentiation of transmitter release and on the prolongation of the synaptic delay. The effects of tetraethylammonium (TEA) and other K+ channel blockers on these parameters were similar to those of 4-AP. Strong depolarizing pulses applied focally to a nerve ending were able to evoke a giant response even in the presence of 1 microM-tetrodotoxin (TTX). The prolongation of the discharge by 4-AP was therefore not caused by repetitive re-excitation of the nerve branches. Both the amplitude and the time course of the giant response were Ca2+ dependent. At a low Mg2+ concentration, the Ca2+ dependence of transmitter release was identical in the presence or absence of 4-AP. Paradoxically, in the presence of 4-AP, addition of 4 mM-Mg2+ considerably increased the Ca2+ dependence of release, whereas in the absence of 4-AP, Mg2+ blocked transmitter release by decreasing its sensitivity to Ca2+. This potentiating interaction between Mg2+ and 4-AP was not seen with TEA or guanidine. In conclusion, 4-AP potentiates ACh release in two different ways in the Torpedo electric organ: it promotes a sustained quantal release of transmitter during several hundreds of milliseconds without any significant change in the maximal synchronous release, it interacts with Mg2+ in such a manner that the sensitivity to Ca2+ of the nerve terminals is increased.


Anion-Exchange Chromatography Coupled to High-Resolution Mass Spectrometry: A Powerful Tool for Merging Targeted and Non-targeted Metabolomics.
In this work, simultaneous targeted metabolic profiling by isotope dilution and non-targeted fingerprinting is proposed for cancer cell studies. The novel streamlined metabolomics workflow was established using anion-exchange chromatography (IC) coupled to high-resolution mass spectrometry (MS). The separation time of strong anion-exchange (2 mm column, flow rate 380 μL min-1, injection volume 5 μL) could be decreased to 25 min for a target list comprising organic acids, sugars, sugar phosphates, and nucleotides. Internal standardization by fully 13C labeled Pichia pastoris extracts enabled absolute quantification of the primary metabolites in adherent cancer cell models. Limits of detection (LODs) in the low nanomolar range and excellent intermediate precisions of the isotopologue ratios (on average <5%, N = 5, over 40 h) were observed. As a result of internal standardization, linear dynamic ranges over 4 orders of magnitude (5 nM-50 μM, R2 > 0.99) were obtained. Experiments on drug-sensitive versus resistant SW480 cancer cells showed the feasibility of merging analytical tasks into one analytical run. Comparing fingerprinting with and without internal standard proved that the presence of the 13C labeled yeast extract required for absolute quantification was not detrimental to non-targeted data evaluation. Several interesting metabolites were discovered by accurate mass and comparing MS2 spectra (acquired in ddMS2 mode) with spectral libraries. Significant differences revealed distinct metabolic phenotypes of drug-sensitive and resistant SW480 cells.


Algorithms Research and Precision Comparison of Different Frequency Combinations of BDS-3\GPS\Galileo for Precise Point Positioning in Asia-Pacific Region.
With the continuous construction and development of the BeiDou navigation satellite system (BDS), its positioning performance is constantly being improved. In this study, the positioning performance of different frequency combinations of BDS-3/GPS/Galileo in the Asia-Pacific region was investigated. The precision products of Wuhan University and the observation data of nine MGEX stations were selected to compare and analyze the B1I\B1C\B2a\B3I and L1\E1 pseudo-range Standard Point Positioning (SPP) and B1IB2a\B1IB3I\B1CB2a\B1CB3I\B2aB3I\L1L2\E1E5a precise point positioning (PPP) performance, while B1I\B3I\L1 SPP and B1IB3I PPP were investigated using BDS-2 with QZSS supplemented with BDS-3 and GPS. The experimental results showed that the positioning precision of BDS-3/GPS/Galileo SPP was in the order of B1C > E1 > L1 > B1I > B3I > B2a, and it was not significantly improved after BDS-2 and QZSS were added. Moreover, for the PPP of different frequency combinations, the convergence speed was in the order of L1L2 > B1IB3I > E1E5a > B1CB3I > B1CB2a > B1IB2a > B2aB3I. After adding BDS-2, B1IB3I improved by about 11% in static mode and 27% in kinematic mode, which was similar to the L1L2 frequency combination. The positioning precision of different frequency combinations of BDS-3/GPS/Galileo was B1IB3I > B1CB3I > L1L2 > E1E5a > B1B2a > B1CB2a > B2aB3I. In static mode, after adding BDS-2, B1IB3I did not show significant improvement in the plane direction, and showed ~61% improvement in the elevation direction, and ~67% in the three-dimensional (3D) direction. In kinematic mode, after adding BDS-2, B1IB3I was improved by about 16% in the E direction, the N direction did not show significant change, it improved by ~38% in the U direction and by ~70% in the 3D direction. In general, the positioning performance of BDS-3 was slightly better than those of GPS and Galileo in the Asia-Pacific region, and it is believed that with the continuous development of BDS, its positioning performance will surely be improved further.


Current status of neonatal follow-up in Canada.
Follow-up programs in Canada collect audit and outcome research data, and provide clinical and preventive health care to extremely premature survivors and other new survivors of neonatal intensive care. Results of a 2001 to 2002 survey of Canadian follow-up programs showed a tremendous variation in the patient populations seen, the timing of visits and the evaluations performed. A description of the new Quebec consortium of follow-up programs is provided and possible future directions are discussed.


Ion trap mass spectrometry for kinetic studies of stable isotope labeled vitamin A at low enrichments.
The role of beta-carotene in chemoprevention of cancers and other chronic diseases generated controversy when subpopulations taking beta-carotene supplements showed increased mortality in clinical trials. Determination of the dynamics of beta-carotene in individual human subjects has emerged as a high priority. Stable isotope labeled beta-carotene tracers can be employed to determine rates of conversion to retinol (vitamin A), but tracer doses must be small to minimize perturbation of endogenous retinoid and carotenoid pools. In such cases, ratios of labeled tracer/endogenous retinol are often low, and quantitative analysis at enrichments of < 1 mol% are unreliable owing to ion-molecule reactions that generate ions at the same mass as the labeled tracer even when no tracer is present. The current study demonstrates improved gas chromatography/mass spectrometry quantification of retinol-d4 and unlabeled retinol, as their tert-butyldimethylsilyl ethers, at low enrichments using an ion trap mass spectrometer operated in selected ion storage mode. Electron ionization of analyte takes place in the ion trap using conditions that eject ions outside the range m/z 390-420, and molecular ions at m/z 400 and 404 from retinol and retinol-d4 are quantified. Using this approach, unlabeled retinol yields a signal close to values calculated from natural isotopic abundances (approximately 0.13%), whereas several quadrupole instruments operated using selected ion monitoring yielded 2-5 times greater signal when no labeled retinol was present.


Environmental reverberation affects processing of sound intensity in right temporal cortex.
Although sound reverberation is considered a nuisance variable in most studies investigating auditory processing, it can serve as a cue for loudness constancy, a phenomenon describing constant loudness perception in spite of changing sound source distance. In this study, we manipulated room reverberation characteristics to test their effect on psychophysical loudness constancy and we tested with magnetoencephalography on human subjects for neural responses reflecting loudness constancy. Psychophysically, we found that loudness constancy was present in strong, but not weak, reverberation conditions. In contrast, the dependence of sound distance judgment on actual distance was similar across conditions. We observed brain activity reflecting behavioral loudness constancy, i.e. inverse scaling of the evoked magnetic fields with distance for weak reverberation but constant responses across distance for strong reverberation from ~210 to 270 ms after stimulus onset. Distributed magnetoencephalography source reconstruction revealed underlying neural generators within the right middle temporal and right inferior anterior temporal lobe. Our data suggest a dissociation of loudness constancy and distance perception, implying a direct usage of reverberation cues for constructing constant loudness across distance. Furthermore, our magnetoencephalography data suggest involvement of auditory association areas in the right middle and right inferior anterior temporal cortex in this process.


Clinical consequences of a polygenic predisposition to benign lower white blood cell counts: Consequences of benign WBC count genetics.
Polygenic variation unrelated to disease contributes to interindividual variation in baseline white blood cell (WBC) counts, but its clinical significance is undefined. We investigated the clinical consequences of a genetic predisposition toward lower WBC counts among 89,559 biobank participants from tertiary care centers using a polygenic score for WBC count (PGSWBC) comprising single nucleotide polymorphisms not associated with disease. A predisposition to lower WBC counts was associated with a decreased risk of identifying pathology on a bone marrow biopsy performed for a low WBC count (odds-ratio=0.55 per standard deviation increase in PGSWBC [95%CI, 0.30 - 0.94], p=0.04), an increased risk of leukopenia (a low WBC count) when treated with a chemotherapeutic (n=1,724, hazard ratio [HR]=0.78 [0.69 - 0.88], p=4.0×10-5) or immunosuppressant (n=354, HR=0.61 [0.38 - 0.99], p=0.04). A predisposition to benign lower WBC counts was associated with an increased risk of discontinuing azathioprine treatment (n=1,466, HR=0.62 [0.44 - 0.87], p=0.006). Collectively, these findings suggest that a WBC count polygenic score identifies individuals who are susceptible to escalations or alterations in clinical care that may be harmful or of little benefit.


Controlled study of cimetidine in the treatment of benign prostatic hypertrophy.
A series of 60 patients with benign prostatic hypertrophy (BPH) was randomly divided into 2 groups; 30 received cimetidine 1 g/day for 4 weeks and 30 received vitamin C 1 g/day for the same period. The study was double-blind. No significant difference between the 2 groups was observed in mean urinary flow, subjective obstructive or irritative symptoms, or prostate size. There was a statistically significant difference in the peak urinary flow rate but this was a result of net deterioration in the control group. Cimetidine was found to be no more active than vitamin C in treating benign prostatic hypertrophy.


Histocompatibility antigens and insulin-dependent diabetes: a study of 20 Brazilian families.
1. The relationship between histocompatibility antigens (HLA) and insulin-dependent diabetes was examined. The relative frequency of HLA and the relative risk were determined for 20 families containing 82 individuals, 23 of whom had insulin-dependent diabetes. The control group contained 102 individuals. 2. The B8, B13, and B15 antigens had the highest relative frequency in the group of diabetic patients, whereas B5, B7 and B12 were lowest. A high relative frequency of histocompatibility antigens was found not only in the diabetic patients, but also in their parents and siblings. There was a predominance of A2B8, A2B15, and A9B15 haplotypes in the diabetic population. The diabetic siblings had identical haplotypes. 3. These data support previous reports suggesting genetic linkage between susceptibility to diabetes and the histocompatibility antigen system.


Pregnancy-Related Mortality and Severe Maternal Morbidity in Rural Appalachia: Established Risks and the Need to Know More.
The Centers for Disease Control and Prevention (CDC) and the American College of Obstetrics and Gynecology have called for researchers to further elucidate medical and social determinants of pregnancy-related death and severe maternal morbidity. This report begins to answer this call in the context of rural Appalachia. This report identifies risk factors exposing women in rural Appalachia to pregnancy-related death and severe maternal morbidity. We also use CDC WONDER data to illustrate rural-urban differences in pregnancy-related death. Rural women nationally die of pregnancy-related causes at a greater rate than urban women. It is unknown how rurality specifically influences pregnancy-related death, but rural women more often embody multiple risk factors associated with negative maternal outcomes. Established risk factors, including high rates of chronic illness and substance abuse, place rural women at risk for severe maternal morbidity and pregnancy-related mortality. These women may also lack the resources to mitigate these risks, including access to high-risk obstetric care. To address these issues and the concerning lack of data, we propose 4 directions for future study: (1) a determination of the prevalence of pregnancy-related death and severe maternal morbidity in this population; (2) an examination of how rural women utilize existing pre- and perinatal resources; (3) better validation concerning surveillance methods of pregnancy-related death and severe maternal morbidity in rural areas; and (4) an exploratory qualitative study of rural women and health care providers.


Muscarinic acetylcholine receptor-mediated phosphoinositide turnover in cultured cerebellar granule cells: desensitization by receptor agonists.
Cultured granule cells prepared from 8-day postnatal rats were used for the study of carbachol-induced phosphoinositide turnover. The addition of carbachol induced a 20- to 30-fold increase in [3H]inositol monophosphate (IP1) accumulation within 30 min in the presence of 20 mM LiCl in granule cells prelabeled with [3H]myoinositol. Carbachol also stimulated the formation of [3H]inositol bisphosphate and [3H]inositol trisphosphate assayed either in the presence or in the absence of lithium; the increase in [3H]inositol triphosphate and [3H]inositol biphosphate synthesis appeared to be faster in the time course but much smaller in amount when compared with the formation of [3H]IP1. The EC50 of carbachol was approximately 7 microM, and the saturation concentration was about 100 microM. This carbachol-induced response was completely blocked by two muscarinic acetylcholine receptor (mAChR) antagonists, atropine and pirenzepine, with a Ki of 0.5 and 120 nM, respectively. Saturation studies of the binding of [3H]N-methylscopolamine and [3H]quinuclidinyl benzilate to mAChRs in intact granule cells revealed the presence of a single class of binding sites with a Kd of 140 and 126 pM, respectively, and a Bmax of approximately 70 fmol/10(6) cells for both ligands. Within 1 hr after pre-exposure of cells to carbachol, the subsequent carbachol-induced [3H]IP1 accumulation was reduced by about 50%, whereas mAChR binding, assessed by using either [3H]N-methylscopolamine or [3H]quinuclidinyl benzilate, was unchanged. A second slower phase of desensitization was associated with a loss of mAChR binding sites; at 18 hr, the decrease of responsiveness was about 80%, whereas the loss of mAChR sites was about 60%.(ABSTRACT TRUNCATED AT 250 WORDS)


ELISpot and ELISA analyses of human IL-21-secreting cells: Impact of blocking IL-21 interaction with cellular receptors.
Interleukin (IL)-21 is crucial for the regulation of lymphocytes and is implicated in autoimmune and other diseases. The relevance of being able to measure human IL-21 prompted us to develop ELISA and ELISpot assays for analysis of IL-21 levels and IL-21-producing cells, respectively. Monoclonal antibodies (mAbs) to IL-21 were made and ELISA and ELISpot assays were developed. The selected detection mAb also neutralized IL-21-mediated activation of human cells. Peripheral blood mononuclear cells (PBMCs) from healthy donors (n=24) were stimulated polyclonally (phytohemagglutinin; PHA) or with antigen (Candida albicans extract and tetanus toxoid). Using ELISpot, high numbers of IL-21-producing cells were detected after PHA activation; lower but positive responses to antigen were seen in approximately 50% of the donors. In contrast, the ELISA detected IL-21 in supernatants from PHA-activated cells but not from antigen-stimulated cells. When analyzing IL-17A in parallel, PHA and antigens induced detectable responses in ELISpot as well as in ELISA. Hypothesizing that the lack of detectable IL-21 levels after antigenic stimulation was due to a combination of low frequencies of IL-21-secreting cells and consumption of IL-21 by cellular receptors during cell culture, PBMCs (n=18) were stimulated in the presence of the neutralizing detection mAb. When preventing IL-21 from interacting with its receptor, increased IL-21 levels were found by ELISA after PHA activation and IL-21 could also be measured after antigen stimulation. ELISpot results were unaffected by the addition of the neutralizing mAb. In conclusion, IL-21 secreted by low frequencies of antigen-specific ex vivo-stimulated PBMC can be difficult to detect by ELISA but prevention of IL-21 interaction with its receptor leads to detectable IL-21 levels. In ELISpot, where the cytokine is captured by mAbs on a solid phase immediately upon secretion, blocking the receptor interaction does not affect the detection of IL-21-secreting cells.


Development and evaluation of a highly sensitive human papillomavirus genotyping DNA chip.
Test of human papillomavirus (HPV) is a useful adjunctive tool of Pap smear to screen cervical cancer. We have developed a novel HPV genotyping DNA chip arrayed by multiple oligonucleotide probes of both L1 and E6/E7 gene sequence of 42 types of anogenital HPV. Consensus PCR products of L1 and E6/E7 gene sequences of HPV are hybridized to arrayed probes on the HPV chip and HPV genotypes are identified by fluorescence scanner. We have comparatively analyzed the value of HPV DNA chip and DNA sequencing in 100 cervical cancer tissues. Overall, 98 cervical cancer tissues were found to harbor DNA sequences of high-risk type HPVs, of which 88 (89.8%) were detected by PCR-sequencing of L1 alone, 98 (100%) by PCR-sequencing of both L1 and E6/E7, and 98 (100%) by HPV DNA chip, respectively. All of the genotypes of HPV detected on sequencing analysis were also found on DNA chip analysis. HPV DNA chip was superior to direct DNA sequencing in detection of mixed infection. These results suggest that HPV DNA chip analysis in the present study is highly accurate for detection and genotyping of HPV and may have potential value as a robust, high-throughput screening test of uterine cervix cancer.


Anterograde axonal transport of peptidylglycine alpha-amidating monooxygenase in rat sciatic nerves.
Axonal transport of peptidylglycine alpha-amidating monooxygenase (PAM) activity was studied in rat sciatic nerves from 12 to 120 h after double ligations. The anterograde axonal transport increased and reached a plateau between 48 and 72 h and then decreased. The flow rate was 100 mm/day, and the molecular mass of the active entity was 70 kDa, which was determined by gel filtration. In contrast, there was no evidence for significant retrograde axonal transport. Anterograde axonal transport of immunoreactive cholecystokinin, a carboxy-terminal-amidated putative neuropeptide, was also found. These results suggest that PAM is transported by a rapid axonal flow and may play a role as a processing enzyme during transport or in the terminals of rat sciatic nerves.


Synaptic vesicles isolated from the electric organ of Torpedo californica and from the central nervous system of Mus musculus contain small ribonucleic acids (sRNAs).
Synaptic vesicles (SVs) are presynaptic organelles that load and release small molecule neurotransmitters at chemical synapses. In addition to classic neurotransmitters, we have demonstrated that SVs isolated from the Peripheral Nervous Systems (PNS) of the electric organ of Torpedo californica, a model cholinergic synapse, and SVs isolated from the Central Nervous System (CNS) of Mus musculus (mouse) contain small ribonucleic acids (sRNAs; ≤ 50 nucleotides) (Scientific Reports, 5:1-14(14918) Li et al. (2015) [1]). Our previous publication provided the five most abundant sequences associated with the T. californica SVs, and the ten most abundant sequences associated with the mouse SVs, representing 59% and 39% of the total sRNA reads sequenced, respectively). We provide here a full repository of the SV sRNAs sequenced from T. californica and the mouse deposited in the NCBI as biosamples. Three data studies are included: SVs isolated from the electric organ of T. californica using standard techniques, SVs isolated from the electric organ of T. californica using standard techniques with an additional affinity purification step, and finally, SVs isolated from the CNS of mouse. The three biosamples are available at https://www.ncbi.nlm.nih.gov/biosample/ SRS1523467, SRS1523466, and SRS1523472 respectively.


Mechanisms of resonant low frequency Raman scattering from metallic nanoparticle Lamb modes.
The low frequency Raman scattering from gold nanoparticle bimodal assemblies with controlled size distributions has been studied. Special care has been paid to determining the size dependence of the Raman intensity corresponding to the quadrupolar Lamb mode. Existing models based on a microscopic description of the scattering mechanism in small particles (bond polarizability, dipole induced dipole models) predict, for any Raman-active Lamb modes, an inelastic intensity scaling as the volume of the nanoparticle. Surprisingly experimental intensity ratios are found to be anomalously much greater than theoretical ones, calling into question this scaling law. To explain these discrepancies, a simple mechanism of Raman scattering, based on the density fluctuations in the nanoparticles induced by the Lamb modes, is introduced. This modeling, in which the nanoparticle is described as an elastic isotropic continuous medium-as in Lamb theory, successfully explains the major features exhibited by low frequency Raman modes. Moreover this model provides a unified picture for any material, suitable for handling both small and large size ranges, as well as non-resonant and resonant excitation conditions in the case of metallic species.


Premature termination codons in the DMD gene cause reduced local mRNA synthesis.
Duchenne muscular dystrophy (DMD) is caused by mutations in the DMD gene leading to the presence of premature termination codons (PTC). Previous transcriptional studies have shown reduced DMD transcript levels in DMD patient and animal model muscles when PTC are present. Nonsense-mediated decay (NMD) has been suggested to be responsible for the observed reduction, but there is no experimental evidence supporting this claim. In this study, we aimed to investigate the mechanism responsible for the drop in DMD expression levels in the presence of PTC. We observed that the inhibition of NMD does not normalize DMD gene expression in DMD. Additionally, in situ hybridization showed that DMD messenger RNA primarily localizes in the nuclear compartment, confirming that a cytoplasmic mechanism like NMD indeed cannot be responsible for the observed reduction. Sequencing of nascent RNA to explore DMD transcription dynamics revealed a lower rate of DMD transcription in patient-derived myotubes compared to healthy controls, suggesting a transcriptional mechanism involved in reduced DMD transcript levels. Chromatin immunoprecipitation in muscle showed increased levels of the repressive histone mark H3K9me3 in mdx mice compared to wild-type mice, indicating a chromatin conformation less prone to transcription in mdx mice. In line with this finding, treatment with the histone deacetylase inhibitor givinostat caused a significant increase in DMD transcript expression in mdx mice. Overall, our findings show that transcription dynamics across the DMD locus are affected by the presence of PTC, hinting at a possible epigenetic mechanism responsible for this process.


Interpersonal problems and negative affect in Borderline Personality and Depressive Disorders in daily life.
Theories of Borderline Personality Disorder (BPD) suggest that interpersonal problems in BPD act as triggers for negative affect and, at the same time, are a possible result of affective dysregulation. Therefore, we assessed the relations between momentary negative affect (hostility, sadness, fear) and interpersonal problems (rejection, disagreement) in a sample of 80 BPD and 51 depressed outpatients at 6 time-points over 28 days. Data were analyzed using multivariate multi-level modeling to separate momentary-, day-, and person-level effects. Results revealed a mutually reinforcing relationship between disagreement and hostility, rejection and hostility, and between rejection and sadness in both groups, at the momentary and day level. The mutual reinforcement between hostility and rejection/disagreement was significantly stronger in the BPD group. Moreover, the link between rejection and sadness was present at all three levels of analysis for the BPD group, while it was localized to the momentary level in the depressed group.


A new method for evaluation of intestinal muscle contraction properties: studies in normal subjects and in patients with systemic sclerosis.
Systemic sclerosis is a connective tissue disease that involves the gastrointestinal (GI) tract. Seventy-five per cent of systemic sclerosis patients experience symptoms arising from oesophagus. The intestine has less frequently been subject for studies than the oesophagus. When the small intestine becomes involved, nausea, vomiting, bloating, diarrhoea and malabsorption may occur. Previous studies have shown decreased and abnormal intestinal motility, dilatation and a stiffer wall. The aim was to study muscle mechanics in systemic sclerosis patients using novel analysis of intestinal muscle contraction force-velocity and power. A volume-controlled duodenal ramp-distension protocol was used in nine patients and eight healthy controls. The wall stretch ratio, tension, shortening velocity and muscle power were computed from pressure and cross-sectional area data recorded by an impedance planimetry system. The tension-stretch ratio relation obtained in patients was shifted to the left, indicating a stiffer wall. The in vivo tension-shortening velocity relationship was quantified using Hill's equation. The maximum preload tension (tension at zero velocity) was lower in the patients than in the healthy controls (P < 0.001). The muscle power was lowest in the patients. An association was found between the duration of the disease and the maximum stretch ratio (P < 0.05). The study represents the first data with application of in vivo muscle force-velocity relations in patients with gastrointestinal diseases. Systemic sclerosis patients had increased stiffness and impaired muscle dynamics of the duodenum. Decreased muscle function and increased wall stiffness may explain the GI symptoms reported in this patient group.


Community-Based Training-Detraining Intervention in Older Women: A Five-Year Follow-Up Study.
This five-year follow-up nonrandomized controlled study evaluated community-based training and detraining on body composition and functional ability in older women. Forty-two volunteers (64.3 ± 5.1 years) were divided into four groups: aerobic training, strength training, combined aerobic and strength, and control. Body composition and physical fitness were measured at baseline, after nine months of training and after three months of detraining every year. After five years of training, body fat decreased, and fat free mass, strength, and chair test performance increased (p < .05) in all training groups. Training-induced favorable adaptations were reversed during detraining but, eventually, training groups presented better values than the control group even after detraining. Thus, nine months of annual training, during a five-year period, induced favorable adaptations on body composition, muscular strength, and functional ability in older women. Three months of detraining, however, changed the favorable adaptations and underlined the need for uninterrupted exercise throughout life.


Maternal Socioeconomic Status Influences the Range of Expectations During Language Comprehension in Adulthood.
In infancy, maternal socioeconomic status (SES) is associated with real-time language processing skills, but whether or not (and if so, how) this relationship carries into adulthood is unknown. We explored the effects of maternal SES in college-aged adults on eye-tracked, spoken sentence comprehension tasks using the visual world paradigm. When sentences ended in highly plausible, expected target nouns (Exp. 1), higher SES was associated with a greater likelihood of considering alternative endings related to the action of the sentence. Moreover, for unexpected sentence endings (Exp. 2), individuals from higher SES backgrounds were sensitive to whether the ending was action-related (plausible) or unrelated (implausible), showing a benefit for plausible endings. Individuals from lower SES backgrounds did not show this advantage. This suggests maternal SES can influence the dynamics of sentence processing even in adulthood, with consequences for processing unexpected content. These findings highlight the importance of early lexical experience for adult language skills.


Prostaglandin receptor EP2 mediates PGE2 stimulated hypercalcemia in mice in vivo.
Prostaglandin E2 (PGE2) can stimulate bone resorption by a cyclic AMP-dependent pathway. Two PGE2 receptors, EP2 and EP4 have been shown to play a role in PGE2 stimulation of osteoclast formation. In primary osteoblastic cell cultures from EP2 wild type (EP2 +/+) mice, PGE2 (0.1 microM) increased cyclic AMP production 3.5-fold, but PGE2 had no effect on cells from mice in which the EP2 receptor had been deleted (EP2 -/-). To examine the role of the EP2 receptor in the resorption response in vivo we injected PGE2 in EP2 -/- mice, and compared them with EP2 +/+ mice. Injection of PGE2 (3 mg/kg, four times daily for three days) in 9- to 12-month-old male mice on a 129 SvEv background increased serum calcium from 9.8 +/- 0.5 to 10.7 +/- 0.3 mg/dl (P < 0.01) in EP2 +/+ mice but not in EP2 -/- mice (10.1 +/- 0.3 vs. 10.2 +/- 0.3 mg/dl). PGE2 injection (6 mg/kg twice a day for three days) in 3-4 month old male mice on a C57 BL/6 X 129 SvEv background increased calcium from 8.2 +/- 0.1 to 9.0 +/- 0.3 mg/dl (P < 0.05) in EP2 +/+ mice but had no effect in EP2-/- mice (8.4 +/- 0.1 vs. 8.3 +/- 0.2 mg/dl). Injection of PGE2 over the calvariae of EP2 +/+ and EP2-/- mice increased the expression of receptor activator of nuclear factor kappaB ligand (RANKL) both locally and in the tibia, but RANKL responses were lower in EP2 -/- mice. We conclude that EP2 receptor plays a role in the hypercalcemic response to PGE2. This impaired response in EP2 -/- mice may be due to decreased ability to stimulate cyclic AMP and in part, to a smaller increase in the expression of RANKL mRNA.


Prognostic factors in stage-I breast cancer: a retrospective study.
We studied the case records of all patients presenting with stage-I breast cancer (tumour < 2 cm, no axillary nodes or distant metastases). All clinical and pathological features were evaluated and findings were correlated with short term treatment failures (local and distant recurrences within 2 years). An early recurrence was seen in 28% patients. There was no significant differences in the mean age at presentation (44 vs 47 years) or menopausal status (8 Vs 7 years). Estrogen receptor status was unknown in all the patients. A positive family history of breast cancer was noted in 40% women with tumour relapse against 6% in the non-relapsed group. Associated fibrocystic mammary dysplasia was found in 80% relapsed cases whereas 60% showed lymphatic invasion and tumour necrosis. Vascular invasion was reported in 40% cases. A poorly differentiated histology fibrocystic mammary dysplasia, lymphatic and vascular invasion and tumour necrosis were poor prognostic factors. It was concluded that adjuvant chemotherapy should be given to all patients presenting with stage-I breast cancer and showing poor prognostic factors regardless of the menopausal status.


Population dynamics and ecology of Arcobacter in sewage.
Arcobacter species are highly abundant in sewage where they often comprise approximately 5-11% of the bacterial community. Oligotyping of sequences amplified from the V4V5 region of the 16S rRNA gene revealed Arcobacter populations from different cities were similar and dominated by 1-3 members, with extremely high microdiversity in the minor members. Overall, nine subgroups within the Arcobacter genus accounted for >80% of the total Arcobacter sequences in all samples analyzed. The distribution of oligotypes varied by both sample site and temperature, with samples from the same site generally being more similar to each other than other sites. Seven oligotypes matched with 100% identity to characterized Arcobacter species, but the remaining 19 abundant oligotypes appear to be unknown species. Sequences representing the two most abundant oligotypes matched exactly to the reference strains for A. cryaerophilus group 1B (CCUG 17802) and group 1A (CCUG 17801(T)), respectively. Oligotype 1 showed generally lower relative abundance in colder samples and higher relative abundance in warmer samples; the converse was true for Oligotype 2. Ten other oligotypes had significant positive or negative correlations between temperature and proportion in samples as well. The oligotype that corresponded to A. butzleri, the Arcobacter species most commonly isolated by culturing in sewage studies, was only the eleventh most abundant oligotype. This work suggests that Arcobacter populations within sewer infrastructure are modulated by temperature. Furthermore, current culturing methods used for identification of Arcobacter fail to identify some abundant members of the community and may underestimate the presence of species with affinities for growth at lower temperatures. Understanding the ecological factors that affect the survival and growth of Arcobacter spp. in sewer infrastructure may better inform the risks associated with these emerging pathogens.


Neutrophil granulocytic cell antigen defined by a monoclonal antibody--its distribution within normal haemic and non-haemic tissue.
Monoclonal antibodies were raised against normal human bone marrow cells. One of the antibodies obtained, monoclonal antibody 3C4 (MA 3C4), the subject of this paper, was characterised by immunofluorescence studies with viable normal peripheral blood and bone marrow cells and by immunoperoxidase studies using paraffin sections. In bone marrow and peripheral blood MA 3C4 reacts selectively with cells of late neutrophilic granulopoiesis (myelocytes, metamyelocytes, and neutrophilic granulocytes). Cells of erythropoiesis, thrombopoiesis and lymphopoiesis are negative. In lymph node and spleen only neutrophils react with MA 3C4. In non-haemic tissue reactivity was seen with epithelial cells of a variety of different gland ducts. Thus the antigen detected by MA 3C4 can serve as a marker for neutrophil differentiation in normal haemopoiesis and as a marker for ductal epithelial cells of a variety of organs within non-haemic tissue. The antigen is formalin-resistant and can be detected in paraffin sections. The antibody thus appears to be a valuable reagent for both haematological research and for routine pathology.


ACE-inhibitors in the treatment of elderly hypertensives.
Angiotensin-converting enzyme inhibitors are gaining acceptance as safe and effective agents for treatment of hypertension. Data on their use specifically in elderly hypertensives, however, are limited. Addressed in this review of the available literature are the questions whether they are effective hypotensives in the elderly, whether their effects are age-related, and what effects, if any, do they have on morbidity and mortality in geriatric hypertension.


Pan-cancer analysis shows that IBSP is a potential prognostic and immunotherapeutic biomarker for multiple cancer types including osteosarcoma.
IBSP is a member of the small integrin-binding ligand N-linked glycoprotein (SIBLING) family that plays a vital role in bone formation, renewal and repair. Emerging evidence revealed that IBSP participated in the tumorigenesis and progression in some cancers. However, its significance in tumour prognosis and immunotherapy is still unknown. In the current study, we studied the role of IBSP in tumorigenesis, tumor diagnosis, genomic heterogeneity, methylation modifications, immune infiltration, and therapy response in pan-cancer. In addition, we constructed a risk score model to assessed the prognostic classification efficiency of IBSP using the co-expression genes of IBSP in osteosarcoma (OS), and analyzed the expression and role of IBSP in OS through a series of assays in vitro. IBSP was upregulated in various cancers compared to the paired normal tissues, and it was strongly correlated with the prognosis, pathological stage, diagnostic accuracy, genomic heterogeneity, methylation modification, immune infiltration, immune and checkpoint. Moreover, the predictive model we established in combination with the clinical characteristics of OS patients showed high survival predictive power in these individuals. The assays in vitro showed that IBSP promoted the proliferation, migration and invasion of OS cells, which further confirmed IBSP's role in cancers. Our research revealed the multifunctionality of IBSP in the tumorigenesis, progression and therapy in various cancers, which demonstrated that IBSP may serve as a potential prognostic biomarker and a novel immunotherapy target in pan-cancer.


Management of lower extremity arterial trauma.
Extremity vascular trauma is common in most urban trauma centers and controversy remains about the optimal management of arterial injuries. We examined the records of 188 patients who had lower extremity arterial trauma from September 1987 to April 1992 to help clarify these issues. There were 142 (75.5%) gunshot wounds, 18 (9.6%) stab wounds, 5 (2.7%) shotgun wounds, and 23 (12.2%) patients with blunt trauma. There were 43 (22.9%) associated venous injuries. There were 10 repair failures in the acute postoperative period. There were no repair failures for the iliac artery. Three failures involved the superficial femoral artery (SFA), six were popliteal, and one tibial. Vein and polytetrafluoroethylene (PTFE) grafts were used to repair the SFA with equal success. Repair of the popliteal artery with PTFE failed in four of five cases, while vein grafts failed in only 2 of 19 cases (p < 0.01). Graft failure was associated with blunt trauma in 8 of 23 patients (35%), and always resulted in amputation. Penetrating injuries accounted for only 2 of 165 (1.2%) failures and were successfully redone with no amputations. Venous injury was present in all SFA failures. Popliteal vein injury was present in two PTFE and two vein grafts that failed. There were no infections of vein or PTFE grafts. In conclusion, PTFE and vein have equal graft patency for the repair of the iliac and femoral arteries. However, the patency of PTFE was significantly worse in the popliteal location. Vein grafts should be used for repair of this vessel. Graft failure and amputation were more common with popliteal and tibial injuries from blunt mechanisms.(ABSTRACT TRUNCATED AT 250 WORDS)


Parental attitudes to presence at induction of paediatric anaesthesia.
Previous studies of parental presence at induction of anaesthesia in children have examined parental reaction to being present and the benefits gained from their presence. This study was undertaken specifically to assess parents' attitudes to being present at induction of their child's anaesthetic. A total of 154 questionnaires were distributed over a two-week period to parents of children presenting to the Day Stay Unit for procedures requiring general anaesthesia. Eighty-eight percent would have liked to be present at induction. Only 41% of parents expected to be present and only 40% of parents were actually present for their child's induction. Of those parents present, 94% felt it helpful to their child, 65% helpful to themselves and 41% helpful to the anaesthetist. No-one felt their presence to have been unhelpful. These results may provide an incentive for anaesthetists to review their current paediatric anaesthetic practices.


Induction of thermotolerance by prostaglandin A in human cells.
Cyclopentenone prostaglandins (PGs) induce the synthesis of heat shock proteins (HSPs) in mammalian cells. Since arachidonic acid metabolites are implicated in the control of fever, we investigated the effect of PG treatment on thermal injury in human K562 erythro-leukemia cells. Prostaglandin A1 (PGA1) was found to protect cells after severe heat shock and to induce a thermotolerant state, which persisted for 24-48 h. Prostaglandins of the B, E, and F type were not effective. Kinetics of thermotolerance induction was comparable to heat-induced heat resistance. Establishment of a thermotolerant state was not a direct effect of PGA1, since it was dependent on de novo protein synthesis and was associated with HSP70 induction. This activity of PGA1 could be part of a protective control mechanism during fever.


2,3-Diarylxanthones as Potential Inhibitors of Arachidonic Acid Metabolic Pathways.
In response to an inflammatory stimulus, arachidonic acid (AA), the main polyunsaturated fatty acid present in the phospholipid layer of cell membranes, is released and metabolized to a series of eicosanoids. These bioactive lipid mediators of inflammation arise physiologically through the action of the enzymes 5-lipoxygenase (5-LOX) and cyclooxygenases (constitutive COX-1 and inducible COX-2). It is believed that dual inhibition of 5-LOX and COXs may have a higher beneficial impact in the treatment of inflammatory disorders rather than the inhibition of each enzyme. With this demand for new dual-acting anti-inflammatory agents, a range of 2,3-diarylxanthones were tested through their ability to interact in the AA metabolism. In vitro anti-inflammatory activity was evaluated through the inhibition of 5-LOX-catalyzed leukotriene B4 (LTB4) formation in human neutrophils and inhibition of COX-1- and COX-2-catalyzed prostaglandin E2 (PGE2) formation in human whole blood. The results showed that some of the studied arylxanthones were able to prevent LTB4 production in human neutrophils, in a concentration-dependent manner. The xanthone with a 2-catechol was the most active one (IC50 ∼ 9 μM). The more effective arylxanthones in preventing COX-1-catalyzed PGE2 production presented IC50 values from 1 to 7 μM, exhibiting a structural feature with at least one non-substituted aryl group. All the studied arylxanthones were ineffective to prevent the formation of PGE2 catalyzed by COX-2, up to the maximum concentration of 100 μM. The ability of the tested 2,3-diarylxanthones to interact with both 5-LOX and COX-1 pathways constitutes an important step in the research of novel dual-acting anti-inflammatory drugs.


Regioselective Sulfenylation of α'-CH3 or α'-CH2 Groups of α,β-Unsaturated Ketones with Heterocyclic Thiols.
A rare regioselective sulfenylation of α'-CH3 or α'-CH2 bonds adjacent to α,β-unsaturated ketones using dimethyl sulfoxide as an oxidant and a substoichiometric amount of aq HI as an additive is described. This methodology employs a strong acid such as aq HI or iodine and exhibits a high regioselectivity without undergoing conjugate addition, which is difficult to achieve under the cross dehydrogenative coupling method.


Malignant hypertension. Recovery of kidney function after renal allograft failure.
A 28-year old patient with malignant hypertension developed endstage renal failure necessitating chronic maintenance hemodialysis for seven months and transplantation of a renal allograft that was rejected within a month. After this, with continued control of the hypertension, the patient's own kidneys gradually resumed function and achieved anendogenous creatinine clearance of 30 ml/min. She has not required further dialysis for more than nine months. Recovery of sufficient renal function to maintain homeostasis, one year after onset of uremia, indicates the prolonged antihypertensive treatment period that may be necessary to reverse the renal arteriolar changes associated with malignant hypertension. This experience further underlines the necessity of moderation in the use of nephrectomy in the management of severe hypertension.


Splice factor mutations and alternative splicing as drivers of hematopoietic malignancy.
Differential splicing contributes to the vast complexity of mRNA transcripts and protein isoforms that are necessary for cellular homeostasis and response to developmental cues and external signals. The hematopoietic system provides an exquisite example of this. Recently, discovery of mutations in components of the spliceosome in various hematopoietic malignancies (HMs) has led to an explosion in knowledge of the role of splicing and splice factors in HMs and other cancers. A better understanding of the mechanisms by which alternative splicing and aberrant splicing contributes to the leukemogenic process will enable more efficacious targeted approaches to tackle these often difficult to treat diseases. The clinical implications are only just starting to be realized with novel drug targets and therapeutic strategies open to exploitation for patient benefit.


Phospholipase A2 complexes with gadolinium (III) and interaction of the enzyme-metal ion complex with monomeric and micellar alkylphosphorylcholines. Water proton nuclear magnetic relaxation studies.
Gadolinium (III) binds competitively with calcium(II) to porcine pancreatic phospholipase A2 (EC 220.127.116.11) and its zymogen. The enzyme-Gd3+ complex exhibits 4% of the hydrolytic activity of the corresponding Ca2+ complex toward a dispersion of dioctanoyllecithin. Dissociation constants for the Gd3+ complex of enzyme and proenzyme were evaluated from water proton relaxation rate (PRR) titrations. At pH 5.8, the dissociation constants for the Gd3+ complexes of enzyme and zymogen are 0.50 and 0.18 mM, respectively. Dissociation constants for the complexes of enzyme with Ca2+, Eu3+, and Tb3+ were evaluated in PRR titrations by competition of these cations with Gd3+ binding. PRR enhancement factors for the Gd3+ complexes of enzyme and proenzyme are 16.4 and 5.8, respectively, at 22 degrees C and 24.3 MHz. Binding of a homologous series of n-alkylphosphorylcholines to the enzyme-Gd3+ complex was investigated through the influence of monomeric and micellar forms of these amphiphiles on the PRR enhancement factor for the enzyme-bound Gd3+. Separate monomer and micelle binding regions were observed in titrations using n-alkylphosphorylcholines with critical micelle concentrations ranging from 15 muM to 13 mM. In every case, the enhancement factors for the enzyme-Gd3+ complexes were significantly greater than that for the tenary complex, enzyme-Gd3+ -monomer. Morever, a synergism was observed in the binding of Gd3+ and micelles to the enzyme. The magnitudes of the PRR enhancement factors for the enzyme-Gd3+ complexes with micelles of n-alkylphosphorylcholines indicate that the bound Gd3+ is freely accessible to the bulk solvent. These results suggest a model for the enzyme-micelle complex in which the active site is spatially removed from the enzyme-micelle interface.


Effects of a diphtheria-tetanus-acellular pertussis vaccine on immune responses in murine local lymph node and lung allergy models.
We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor beta levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy.


Development and use of an attenuated total reflectance/fourier transform infrared (ATR/FT-IR) spectral database to identify foreign matter in cotton.
The presence of foreign matter in cotton seriously affects the cotton grade and thus the price per bale paid by the spinner to the grower, the efficiency of the spinning and ginning operations, and the quality of the final woven product. Rapid identification of the nature of the extraneous matter in cotton at each stage of cleaning and processing is necessary to permit actions to eliminate or reduce its presence and improve efficiency and quality. Although several instruments are being successfully employed for the measurement of contamination in cotton fibers based on particle size/weight, no commercial instrument is capable of accurate qualitative identification of contaminants. To this end, ATR/FT-IR spectra of retrieved foreign matter were collected and subsequently rapidly matched to an authentic spectrum in a spectral database. The database includes contaminants typically classified as "trash", cotton plant parts (hull, shale, seed-coat fragments, bract, cacyx, leaf, bark, sticks, and stems) and grass plant parts (leaf and stem); "foreign objects and materials", synthetic materials (plastic bags, film, rubber, bale wrapping and strapping); organic materials (other fibers, yarns, paper, feathers, and leather); plus entomological and physiological sugars and inorganic materials (sand and rust). The spectral matching resulted in consistently high-score identification of the foreign matter based on chemical composition, irrespective of its particle size. The method is envisioned to be employed with stand-alone rugged infrared instrumentation to provide specific identification of extraneous materials in cotton as opposed to only general classification of the type by particle size or shape.


A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.
GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role.


Insulinoma: an evaluation by a single institution.
Insulinoma is a rare pancreatic islet cell tumour that is associated with hypoglycaemia. Diagnosis of the disease, localisation of the tumour and surgical therapy may be challenging and the aim of this study is to evaluate the problems concerning insulinoma. The surgical records of patients who were operated on for insulinoma at Hacettepe University Department of General Surgery between January 1980 and December 2006 were evaluated retrospectively. The evaluated parameters were the gender and ages of the patients with symptoms, signs, diagnostic tools and surgical methods. Twenty-six patients were included in the study. There were 17 male and nine female patients. The median age was 34. The median diagnostic period was 285 days. Abdominal computer tomography was the most frequently used diagnostic method. A total of 15 enucleations, nine distal pancreatectomies and three pancreaticoduodenectomies were performed. Histopathologically most of the tumours were benign islet cell tumours. There are still difficulties in the diagnosis, localisation and histopathologic evaluation of insulinoma. Appropriate pre-operative evaluation, through exploration and palpation of the pancreas during the surgery, as well as experienced centres are important to increase the success of the surgery of insulinoma.


A Survey of Cone-beam Computed Tomographic Use among Endodontic Practitioners in the United States.
Cone-beam computed tomographic (CBCT) imaging is an emerging technology for clinical endodontic practice. The aim of this study was to investigate the acceptance, accessibility, and usage of CBCT imaging among American Association of Endodontists members in the United States by means of an online survey. An invitation to participate in a web-based survey was sent to 3076 members of the American Association of Endodontists. The survey consisted of 8 questions on demographics, access to CBCT machines, field of view (FOV), frequency of use for particular applications, and reasons in case CBCT was not used. A total of 1083 participants completed the survey, giving an overall completed response rate of 35.2%; 80.30% of the participants had access to a CBCT scan, of which 50.69% (n = 443) were on-site and 49.31% (n = 431) were off-site, and 19.30% of all respondents denied having access to CBCT imaging. Limited FOV was used by 55.26% participants, 22.37% used larger FOV formats, and the remaining 22.37% were not sure about the format. There was a significantly greater usage of CBCT technology in residency programs (n = 78/84 [92.86%]) compared with practitioners who had finished an endodontic specialty program (n = 796/999 [79.68%]) (χ2 = 10.30, P = .02). Practitioners used CBCT imaging "frequent" or "always" for internal or external resorptions (47.28%), preoperatively for surgical retreatment or intentional replantation (45.34%), missing canals (25.39%), preoperatively for nonsurgical retreatments (24.91%), differential diagnosis (21.16%), identifying periradicular lesions (18.26%), calcified cases (13.54%), immature teeth (4.71%), and to assess healing (3.87%). There was a significant difference in on-site and off-site CBCT imaging use for any of these applications (P < .001). Prevalent reasons for not using CBCT technology were cost (53.79%) and lack of installation space (8.29%). General concerns were expressed about resolution limitations, radiation exposure, and cost to the patient. There is a widespread application of CBCT technology in endodontic practice; however, results from the survey also confirmed that the benefit versus risk ratio should always be in favor of the patient if CBCT scans are taken.


Estimation on the self recovery behavior of low-conductivity layer in landfill final cover by laboratory conductivity tests.
This study examined the application of a Self Recovering Sustainable Layer (SRSL) as a landfill final cover. Low-conductivity layers in landfill covers are known to have problems associated with cracking as a result of the differential settlement or climatic changes. A SRSL is defined as a layer with chemical properties that reduces the increased hydraulic conductivity resulting from cracking by forming low-conductivity precipitates of chemicals contained in the layer. In this study, the formation of precipitates was confirmed using a batch test, spectroscopic analysis and mineralogical speciation tests. The possibility of secondary contamination due to the chemicals used for recovery was evaluated using a leaching test. A laboratory conductivity test was performed on a single layer composed of each chemical as well as on a 2-layer system. The recovery performance of the SRSL was estimated by developing artificial cracks in the specimens and observing the change in hydraulic conductivity as a function of time. In the laboratory conductivity test, the hydraulic conductivity of a 2-layer system as well as those of the individual layers that comprise the 2-layer system was estimated. In addition sodium ash was found to enhance the reduction in conductivity. A significant increase in conductivity was observed after the cracks developed but this was reduced with time, which indicated that the SRSL has a proper recovering performance. In conclusion, a SRSL can be used as a landfill final cover that could maintain low-conductivity even after the serious damages due to settlement.


The cellular basis of self renewal in culture by human acute myeloblastic leukemia blast cell progenitors.
Blast cells from patients with Acute Myeloblastic Leukemia (AML) were separated according to cell size using velocity sedimentation under unit gravity. Fractions obtained in this way were plated in methyl cellulose with a growth stimulator present in media conditioned by leukocytes in the presence of phytohemagglutinin (PHA-LCM). Colonies of blast cells form under these conditions. Pooled cell suspensions from such colonies were plated in microwells; the plating efficiency of such suspensions is a measure of blast progenitor self-renewal occurring in the original blast colonies. Self-renewal assays on each fraction indicated that self renewal among blast progenitors is heterogeneously distributed with subpopulations differing in renewal capacities. The results are consistent with the view that blast cell subpopulations in AML undergo a series of transitions associated with decreasing self renewal capacity, analogous to that observed in normal hemopoiesis, where proliferative capacity decreases with increasing differentiation.


'Isn't it ironic?' Beliefs about the unacceptability of emotions and emotional suppression relate to worse outcomes in fibromyalgia.
Beliefs about the unacceptability of experiencing and expressing emotions have been found to be related to worse outcomes in people with persistent physical symptoms. The current study tested mediation models regarding emotional suppression, beliefs about emotions, support-seeking and global impact in fibromyalgia. One hundred eighty-two participants took part in an online questionnaire testing potential mechanisms of this relationship using mediation analysis. The model tested emotional suppression and affective distress as serial mediators of the relationship between beliefs about emotions and global impact. In parallel paths, two forms of support-seeking were tested (personal/emotional and symptom-related support-seeking) as mediators. Emotional suppression and affective distress significantly serially mediated the relationship between beliefs about emotions and global impact. Neither support-seeking variable significantly mediated this relationship. Results indicate a potential mechanism through which beliefs about emotions and global impact might relate which might provide a theoretical basis for future research on treatments for fibromyalgia.


Pharmacokinetics of cimetidine in critically ill children.
The pharmacokinetic behavior of cimetidine has not been described in children, and there is no authoritative guideline on cimetidine dosage for children. Cimetidine pharmacokinetics were studied after a single intravenous dose and during three, incremental rates of continuous infusion in critically ill children. The mean elimination half-life of cimetidine was 1.44 +/- 0.41 hours. Compared to adults, these children had a relatively faster clearance (14.21 +/- 2.85 ml/min/kg) of cimetidine and a larger apparent distribution volume (2.13 +/- 0.63 l/kg). Based on our results, it appears rational to initiate cimetidine at a daily dose of 24 mg/kg in critically ill children.


Identification of essential arginine residue(s) for Mg-ATP binding of human argininosuccinate synthetase.
Human argininosuccinate synthetase (ASS) activity was found to be inactivated by alpha-dicarbonyls such as 1,2-cyclohexanedione and phenylglyoxal in accordance with pseudo first-order kinetics. The enzyme was almost completely protected from this inactivation by Mg-ATP and partially by its analogues. The strongest protective effect against inactivation was found with Mg-ATP, followed by Mg-ADP, AMP, adenosine and Mg-inorganic pyrophosphate. These results suggest the importance of arginine residue(s) for Mg-ATP binding. We determined the amino acid sequence of the peptide with the highest specific radioactivity derived from ASS which had been labeled with [14C]phenylglyoxal and then cleaved by cyanogen bromide treatment. The sequence obtained, PEFYNRFKGRNDLM, corresponds to residues 148-161 of the amino acid sequence deduced from the cDNA nucleotide sequence determined by Bock et al. [Nucleic Acids Res 11:6505-6512, 1983], and has a high homology with the sequences of ATP-binding sites proposed for several ATP-requiring enzymes.


Functionalized gum acacia-activated carbon-CaO/NiO nanocomposite for potential photocatalytic removal of organic pollutants from water.
A functionalized gum acacia-activated carbon-CaO/NiO nanocomposite was synthesized using an eco-friendly sol-gel method. The formed nanocomposite was designed to apply various light sources to enhance the improved removal of organic dyes such as methylene blue, methyl orange, methyl red, and rhodamine B from aqueous media. The band gap energies of CaO, NiO nanoparticles and gum acacia-activated carbon were 3.54, 4.28, and 5.34 eV, respectively, corresponding to a reflection edge of 350, 290, and 232 nm, respectively. The surface area of the synthesized nanocomposite was measured to be 17.892 m2 g-1. Sunlight and 20 mg L-1 of the nanocomposite quenched the dyes (methylene blue, 99.7%; methyl orange, 98.3%; methyl red, 96.7%; and rhodamine B, 93.5%) after 120, 100, 100, and 75 min of irradiation, respectively. However, after 80, 100, 100, and 75 min, the percentage of dyes under UV light irradiation was 98.6%, 95.8%, 98.4%, and 94.2% for methylene blue, methyl orange, methyl red, and rhodamine B, respectively. The nanocomposite showed excellent stability after five cycles of dye reduction.


Congenital smooth muscle hamartoma of the skin.
A 2-month-old white girl had a congenital, tan-colored, slightly elevated, 3 x 2-cm plaque on the left midback. Clinically, the lesion was suspected to be a solitary mastocytoma. Rubbing the lesion produced a transient erythema and edema that was similar to Darier sign seen in mastocytoma. Analysis of a skin biopsy specimen revealed a smooth muscle hamartoma; special stains did not show evidence of increased numbers of mast cells. This relatively uncommon condition can be confused with a variety of other cutaneous diseases. Light microscopic examination of a skin biopsy specimen establishes the diagnosis. A review of the approximately 50 cases reported in the literature showed that there is no known associated systemic involvement or malignant transformation. The clinical lesions usually become less prominent with time.


PT-symmetric wave Chaos.
We study a new class of chaotic systems with dynamical localization, where gain or loss mechanisms break the Hermiticity, while allowing for parity-time (PT) symmetry. For a value gamma{PT} of the gain or loss parameter the spectrum undergoes a spontaneous phase transition from real (exact phase) to complex values (broken phase). We develop a one parameter scaling theory for gamma{PT}, and show that chaos assists the exact PT phase. Our results have applications to the design of optical elements with PT symmetry.


The motile major sperm protein (MSP) of Ascaris suum forms filaments constructed from two helical subfilaments.
The amoeboid motility nematode sperm is mediated by cytoskeletal filaments composed of major sperm protein (MSP). We have used electron microscopy and image processing to show that MSP filaments are constructed from two subfilament strands which are themselves formed from a helical arrangement of subunits. The subfilaments are based on left-handed helices of pitch 9 nm that then coil along right-handed helical tracks of pitch 22.5 nm to form filaments. The subfilaments appear to be indistinguishable from the helices present in orthorhombic crystals of MSP. Because in filaments the subfilaments are themselves helical, not all subunits are able to participate in protein-protein interactions between different strands. One consequence of this interaction geometry is that the same molecular interactions that function to assemble subfilaments into filaments can also be used to assemble filaments into larger supramolecular assemblies such as the macrofibres formed in vitro and the fibre bundles found in vivo in sperm pseudopods. These results indicate the importance of filament bundling in addition to vectorial filament assembly in amoeboid cell motility.


Evaluation and Transcriptome Analysis of the Novel Oleaginous Microalga Lobosphaera bisecta (Trebouxiophyceae, Chlorophyta) for Arachidonic Acid Production.
Arachidonic acid (AA) is an omega-6 long-chain polyunsaturated fatty acid and is important for human health. The coccoid green microalga Lobosphaera bisecta has been reported to be able to accumulate high AA content under certain conditions. Nutrient management and light intensity had significant effects on the biomass and accumulation of lipids and AA in L. bisecta SAG2043. Both a high nitrogen concentration (18 mM) and high light intensity (bilateral light-300 μmol m-2 s-1) were beneficial to the growth of L. bisecta, and the replacement of culture medium further enhanced the biomass, which reached 8.9 g L-1. Low nitrogen concentration (3.6 mM) and high light significantly promoted the accumulation of lipids and AA. The highest lipid and AA content reached 54.0% and 10.8% of dry weight, respectively. Lipid compositions analysis showed that 88.2% of AA was distributed within the neutral lipids. We then reconstructed the lipid metabolic pathways of L. bisecta for the first time, and demonstrated that the upregulation of a key desaturase and elongase in the Δ6 pathway was conducive to the accumulation of fatty acids toward AA synthesis. L. bisecta SAG2043 exhibits high biomass, lipid and AA production. It may be a potential candidate for AA production.


[Molecular diagnosis in hematologic malignancies].
Recent advances in molecular diagnosis in the hematological laboratory have greatly contributed to the diagnosis and treatment of hematologic malignancies, such as leukemia and lymphoma. The pathogenesis of leukemia and lymphoma has been disclosed by the analyses of genetic abnormalities in patients; abnormal gene expression may induce derangement in the control of cellular proliferation. Based on these genetic abnormalities, gene-targeted therapy has been introduced as a new approach to treating hematologic malignancies. We discuss here the usefulness of the molecular diagnosis in clinical hematology.


MHC class I is required for peripheral accumulation of CD8+ thymic emigrants.
MHC molecules influence the fate of T lymphocytes at two important stages of their differentiation. Recognition of self peptide/MHC complexes in the thymus determines whether immature T cells should live and mature into immunocompetent T cells or whether they should die. In the periphery, recognition of Ags presented by MHC molecules induces T cell activation, proliferation, and differentiation into effector/memory T cells. We describe in this work a third role that MHC molecules play in T cell physiology. CD8+ thymic emigrants require presence of MHC class I molecules in the periphery to seed the peripheral lymphoid organs. Numbers of CD8+ T cells are reduced severely in both the thymus and the periphery of beta2-microglobulin-deficient (beta2m[-/-]) mice. When grafted with wild-type (beta2m[+/+]) thymic epithelium, immature beta2m(-/-) T cells that populate the graft develop into functional mature CD8+ cells. However, significant numbers of peripheral CD8+ cells in grafted beta2m(-/-) mice can be observed only after injection of MHC class I-expressing cells in the periphery. Thus, naive T cells in the periphery do not passively await antigenic stimulation, but actively engage in interactions with self MHC molecules that may promote their survival.


Multicentric Osteolysis Nodulosis Arthropathy Syndrome Simulating Juvenile Idiopathic Arthritis in an Adult Female: A Case Report and a Literature Review.
Multicentric osteolysis, nodulosis, and arthropathy (MONA) syndrome is one of the rare genetic skeletal dysplasias, inherited as an autosomal recessive disorder, which predominantly involves carpal and tarsal bones with characteristic osteolytic lesions and can be misdiagnosed as juvenile idiopathic arthritis or rheumatoid arthritis. MONA syndrome includes diseases involving two genes: the matrix metalloproteinase 2 (MMP2) gene and matrix metalloproteinase 14 (MMP14). Both genes are assumed to cause phenotype variants of the same disease. Older patients may manifest some arthritic features, especially in the wrist, and minute pathological fractures can occur as well. These patients may be misdiagnosed as inflammatory arthritis and physicians might prescribe corticosteroid and disease-modifying immunosuppressive agents. Therefore, physicians should carefully evaluate genetic skeletal dysplasia to make a correct diagnosis and avoid unnecessary pharmacological intervention. We report a case of MONA syndrome in an adult female who came to our facility for an intensive rehabilitation program.


Overlapping Lower Extremity Total Joint Arthroplasty Does Not Increase the Risk of 90-Day Complications.
Although total hip arthroplasty and total knee arthroplasty commonly overlap, there are concerns about the safety and quality of this scenario. The objectives of this study were to (1) compare the operative time and the incidence of 90-day complications between overlapping and nonoverlapping total joint arthroplasties; and (2) evaluate the effect of the duration of overlap on operative time and the incidence of 90-day complications. A total of 9192 patients who underwent primary total hip arthroplasty or total knee arthroplasty at a large academic hospital from 2005 to 2014 were identified. A surgery was defined as overlapping if it had an incision to closure overlap time of at least 1 minute with any other surgery performed by the same surgeon. A total of 2669 (29%) patient procedures were classified as overlapping. Operative times and 90-day complications were compared between overlapping and nonoverlapping surgeries. Mixed effects regression models were used to assess the independent effects of overlapping surgeries. After adjusting for baseline characteristics, operative times were longer for the overlapping surgery group (P<.001). Overlapping surgeries had fewer thromboembolic events (P=.003) and periprosthetic joint infections (P=.039). Wound dehiscence (P=.662), superficial infection (P=.161), and wound hematoma (P=.511) were similar between the 2 groups. Operative times increased with increasing duration of overlap (P<.001); however, there was no association between duration of overlap and 90-day complications (P>.05 for all). Although overlapping surgeries had increased operative times, they did not appear to increase the risk of perioperative complications. This information may be helpful for scheduling overlapping procedures and counseling patients. [Orthopedics. 2018; 41(5):e695-e700.].


Faisalabad histiocytosis mimics Rosai-Dorfman disease: brothers with lymphadenopathy, intrauterine fractures, short stature, and sensorineural deafness.
Rosai-Dorfman disease (RDD) is a rare, sporadic histiocytic disorder characterized by painless but protracted lymphadenopathy. Its etiology remains unclear. The observation of congenital disease and reports of familial cases with seven pairs of siblings including three sets of identical twins suggests a genetic predisposition in some patients with this condition. We now report two brothers of consanguineous Palestinian parents, whose lymphadenopathy, lymph node histology, and polyclonal hypergammaglobulinemia indicated RDD. The presence of intrauterine fractures, short stature, and sensorineural hearing impairment suggested a rare familial form of the disorder. Moynihan et al. recently described a Pakistani family with a familial histiocytic disorder highly reminiscent of the brothers reported here, whose lymph node morphology was apparently consistent with RDD as well. The presence of sensorineural deafness, short stature, and joint contractures, however, suggested a separate, rare autosomal recessive syndrome referred to as Faisalabad histiocytosis, after the family's place of origin. We believe that the brothers described here represent a second family with Faisalabad histiocytosis, which mimics RDD histologically.


Carboxymethyl cellulase production optimization from Glutamicibacter arilaitensis strain ALA4 and its application in lignocellulosic waste biomass saccharification.
In this context, carboxymethyl cellulase (CMCase) production from Glutamicibacter arilaitensis strain ALA4 was initially optimized by one factor at a time (OFAT) method using goat dung as proficient feedstock. Two-level full factorial design (25 factorial matrix) using first-order polynomial model revealed the significant (p < 0.05) influence of pH, moisture, and peptone on CMCase activity. Central composite design at N = 20 was further taken into account using a second-order polynomial equation, and thereby liberated maximum CMCase activity of 4925.56 ± 31.61 U/g in the goat dung medium of pH 8.0 and 100% moisture containing 1% (w/w) peptone, which was approximately two fold increment with respect to OFAT method. Furthermore, the partially purified CMCase exhibited stability not only at high pH and temperature but also in the presence of varied metal ions, organic solvents, surfactants, and inhibitors with pronounced residual activities. The enzymatic hydrolysis using partially purified CMCase depicted the maximum liberation of fermentable sugars from alkali pretreated lignocellulosic wastes biomass in the order of paddy straw (13.8 ± 0.15 mg/g) > pomegranate peel (9.1 ± 0.18 mg/g) > sweet lime peel (8.37 ± 0.16 mg/g), with saccharification efficiency of 62.1 ± 0.8, 40.95 ± 0.4, and 37.66 ± 0.4%, respectively after 72 hr of treatment.


Epidemiology of neurodegeneration in American-style professional football players.
The purpose of this article is to review the history of head injuries in relation to American-style football play, summarize recent research that has linked football head injuries to neurodegeneration, and provide a discussion of the next steps for refining the examination of neurodegeneration in football players. For most of the history of football, the focus of media reports and scientific studies on football-related head injuries was on the acute or short-term effects of serious, traumatic head injuries. Beginning about 10 years ago, a growing concern developed among neurologists and researchers about the long-term effects that playing professional football has on the neurologic health of the players. Autopsy-based studies identified a pathologically distinct neurodegenerative disorder, chronic traumatic encephalopathy, among athletes who were known to have experienced concussive and subconcussive blows to the head during their playing careers. Football players have been well represented in these autopsy findings. A mortality study of a large cohort of retired professional football players found a significantly increased risk of death from neurodegeneration. Further analysis found that non-line players were at higher risk than line players, possibly because of an increased risk of concussion. Although the results of the studies reviewed do not establish a cause effect relationship between football-related head injury and neurodegenerative disorders, a growing body of research supports the hypothesis that professional football players are at an increased risk of neurodegeneration. Significant progress has been made in the last few years on detecting and defining the pathology of neurodegenerative diseases. However, less progress has been made on other factors related to the progression of those diseases in football players. This review identifies three areas for further research: (a) quantification of exposure - a consensus is needed on the use of clinically practical measurements of blows to the head among football players; (b) genetic susceptibility factors - a more rigorous set of unbiased epidemiological and clinical studies is needed before any causal relationships can be drawn between suspected genetic factors, head injury, and neurodegeneration; and (c) earlier detection and prevention of neurodegenerative diseases.


Ph2PCH2CH2B(C8H14) and Its Formaldehyde Adduct as Catalysts for the Reduction of CO2 with Hydroboranes.
We study two metal-free catalysts for the reduction of CO2 with four different hydroboranes and try to identify mechanistically relevant intermediate species. The catalysts are the phosphinoborane Ph2P(CH2)2BBN (1), easily accessible in a one-step synthesis from diphenyl(vinyl)phosphine and 9-borabicyclo[3.3.1]nonane (H-BBN), and its formaldehyde adduct Ph2P(CH2)2BBN(CH2O) (2), detected in the catalytic reduction of CO2 with 1 as the catalyst but properly prepared from compound 1 and p-formaldehyde. Reduction of CO2 with H-BBN gave mixtures of CH2(OBBN)2 (A) and CH3OBBN (B) using both catalysts. Stoichiometric and kinetic studies allowed us to unveil the key role played in this reaction by the formaldehyde adduct 2 and other formaldehyde-formate species, such as the polymeric BBN(CH2)2(Ph2P)(CH2O)BBN(HCO2) (3) and the bisformate macrocycle BBN(CH2)2(Ph2P)(CH2O)BBN(HCO2)BBN(HCO2) (4), whose structures were confirmed by diffractometric analysis. Reduction of CO2 with catecholborane (HBcat) led to MeOBcat (C) exclusively. Another key intermediate was identified in the reaction of 2 with the borane and CO2, this being the bisformaldehyde-formate macrocycle (HCO2){BBN(CH2)2(Ph2P)(CH2O)}2Bcat (5), which was also structurally characterized by X-ray analysis. In contrast, using pinacolborane (HBpin) as the reductant with catalysts 1 and 2 usually led to mixtures of mono-, di-, and trihydroboration products HCO2Bpin (D), CH2(OBpin)2 (E), and CH3OBpin (F). Stoichiometric studies allowed us to detect another formaldehyde-formate species, (HCO2)BBN(CH2)2(Ph2P)(CH2O)Bpin (6), which may play an important role in the catalytic reaction. Finally, only the formaldehyde adduct 2 turned out to be active in the catalytic hydroboration of CO2 using BH3·SMe2 as the reductant, yielding a mixture of two methanol-level products, [(OMe)BO]3 (G, major product) and B(OMe)3 (H, minor product). In this transformation, the Lewis adduct (BH3)Ph2P(CH2)2BBN was identified as the resting state of the catalyst, whereas an intermediate tentatively formulated as the Lewis adduct of compound 2 and BH3 was detected in solution in a stoichiometric experiment and is likely to be mechanistically relevant for the catalytic reaction.


Linguistic and developmental influences on superordinate facial configuration categorization in infancy.
Humans perceive emotions in terms of categories, such as "happiness," "sadness," and "anger." To learn these complex conceptual emotion categories, humans must first be able to perceive regularities in expressive behaviors (e.g., facial configurations) across individuals. Recent research suggests that infants spontaneously form "basic-level" categories of facial configurations (e.g., happy vs. fear), but not "superordinate" categories of facial configurations (e.g., positive vs. negative). The current studies further explore how infant age and language impact superordinate categorization of facial configurations associated with different negative emotions. Across all experiments, infants were habituated to one person displaying facial configurations associated with anger and disgust. While 10-month-olds formed a category of person identity (Experiment 1), 14-month-olds formed a category that included negative facial configurations displayed by the same person (Experiment 2). However, neither age formed the hypothesized superordinate category of negative valence. When a verbal label ("toma") was added to each of the habituation events (Experiment 3), 10-month-olds formed a category similar to 14-month-olds in Experiment 2. These findings intersect a larger conversation about the nature and development of children's emotion categories and highlight the importance of considering developmental processes, such as language learning and attentional/memory development, in the design and interpretation of infant categorization studies.


Upper limb module in non-ambulant patients with spinal muscular atrophy: 12 month changes.
Recent studies have suggested that in non-ambulant patients affected by spinal muscular atrophy the Upper Limb Module can increase the range of activities assessed by the Hammersmith Functional Motor Scale Expanded. The aim of this study was to establish 12-month changes in the Upper Limb Module in a cohort of non-ambulant spinal muscular atrophy patients and their correlation with changes on the Hammersmith Functional Motor Scale Expanded. The Upper Limb Module scores ranged between 0 and 17 (mean 10.23, SD 4.81) at baseline and between 1 and 17 at 12 months (mean 10.27, SD 4.74). The Hammersmith Functional Motor Scale Expanded scores ranged between 0 and 34 (mean 12.43, SD 9.13) at baseline and between 0 and 34 at 12 months (mean 12.08, SD 9.21). The correlation betweeen the two scales was 0.65 at baseline and 0.72 on the 12 month changes. Our results confirm that the Upper Limb Module can capture functional changes in non-ambulant spinal muscular atrophy patients not otherwise captured by the other scale and that the combination of the two measures allows to capture changes in different subgroups of patients in whom baseline scores and functional changes may be influenced by several variables such as age.


[Incidence of double-nucleated heart muscle fibers in hearts with dilated cardiomyopathy and secondary pressure or volume-induced hypertrophy].
Highly differentiated tissue as myocardium grows by amitosis. This direct nuclear partition is mirrored in double-nuclear muscle fibers. In this study we compared the occurrence of double-nuclear muscle fibers in normal hearts (n = 26) with the relations for primary (n = 17) and for secondary (n = 20) hypertrophy. In normal myocardium we found an average of 9.2 +/- 0.8% of double nuclei. Hearts hypertrophic due to valvular disease or systemic hypertension show higher (14.9 +/- 2.7) dilative cardiomyopathies (primary hypertrophy) and a significantly lower (5.4 +/- 0.7) number of double nuclei. Double nuclear counting is a simple method to distinguish a primary from a secondary hypertrophy in uncertain cases. The biological consequence of this difference, however, is not yet clear.


Assessment of pain in cervical dentinal sensitivity studies. A review.
Traditionally cervical dentinal sensitivity (CDS) has been evaluated mainly subjectively on the basis of the individual patient's subjective response, e.g., in the form of verbal rating and visual analogue scales and questionnaires. The stimuli used for evaluating this response can be grouped into 4 main categories: mechanical, chemical, electrical and thermal. This review of the literature, however, indicates that there are problems in evaluating patient subjective response to these various test stimuli used in the assessment and treatment of CDS. Opinions also vary as to the reliability of some of these methods of assessment, although recently, efforts have been made to develop controlled reproducible stimuli more suited to the evaluation of CDS. Currently no single method of eliciting and assessing CDS may be considered ideal. Further research is required to evaluate suitable methodology for the quantification of realistic test stimuli under controlled clinical conditions, whereby the subjective response may be objectively measured by the investigator.


Non-neoplastic epithelial alterations of the vulva: recognition assessment and comparisons of terminologies used among the various specialties.
To assess the recognition of non-neoplastic epithelial alterations of the vulva and to compare terminologies used for these lesions by various specialties, we performed a clinical and dermatopathologic review of all of the cases diagnosed as non-neoplastic epithelial alterations of the vulva that were followed by one gynecologist. Forty-five initial clinical and pathologic diagnoses made by a group of 14 general surgical pathologists during a 15-year period were compared to the diagnoses made by two dermatopathologists at the time of review. Comparison of diagnoses between the three specialties revealed two types of disparities. The first represented differences in nomenclature. Although all parties frequently agreed on a diagnosis of lichen sclerosus, which represented the most frequent histologic diagnosis, the dermatopathologists did not use the term squamous hyperplasia for any case. Of greater significance was the second type of disparity identified, i.e., failure of the gynecologist and general surgical pathologist to identify uncommon dermatoses in eight cases. Concordance in diagnosis among the dermatopathologists was found in 43 of the 45 cases. These findings are consistent with the view that non-neoplastic epithelial alterations of the vulva are the same as elsewhere in the skin and that terms such as vulvar dystrophy or squamous hyperplasia are not meaningful or helpful in identifying or treating vulvar dermatoses. Unfamiliarity with specific dermatoses and the modified appearance of a dermatosis when occurring on the vulva might cause recognition failure by the gynecologist and general surgical pathologist. Entity recognition might be greatly improved if non-neoplastic vulvar lesions are approached as specific dermatoses rather than being labeled as squamous hyperplasias or vulvar dystrophies. Careful histories and physical examinations aid in identifying less common vulvar dermatoses. Referral to a dermatologist/dermatopathologist is indicated when the diagnosis is in doubt or if the response to treatment is poor.


[Use of tamsulosin for a prevention of acute urinary retention in the perioperative period in patients undergoing to surgical procedures].
The perioperative management of patients involves multiple aspects. Acute urinary retention (AUR) is one of the possible postoperative complications. Alpha-adrenoblockers are commonly used for treatment and prevention of AUR. Tamsulosin is the most often prescribed drug; there are a lot of studies devoted to its use in different patient subgroups. The aim of our study was to evaluate the efficiency of perioperative use of tamsulosin for the prevention of postoperative AUR. A literature review from January 2013 to June 2023 in Scopus and PubMed databases was carried out. According to the results, tamsulosin results in a significant reduction in the risk of postoperative AUR. A personalized approach allows to overcome difficulties in the perioperative management of patients and significantly improve their quality of life/satisfaction from treatment.


[Content of DNA in cells of Escherichia coli carrying standard R-plasmids].
DNA content was studied in Escherichia coli K12 cells carrying conjugative R plasmids. Cultures at the exponential growth phase were used for the fractionation of nucleic acids. The content of total and chromosomal DNA was found to be much lower in the presence of R plasmids than in the strain carrying no plasmids. The content of RNA also decreased in the cells of E. coli in the presence of R plasmids.