Insights into Ubiquitination from the Unique Clamp-like Binding of the RING E3 AO7 to the E2 UbcH5B.
RING proteins constitute the largest class of E3 ubiquitin ligases. Unlike most RINGs, AO7 (RNF25) binds the E2 ubiquitin-conjugating enzyme, UbcH5B (UBE2D2), with strikingly high affinity. We have defined, by co-crystallization, the distinctive means by which AO7 binds UbcH5B. AO7 contains a structurally unique UbcH5B binding region (U5BR) that is connected by an 11-amino acid linker to its RING domain, forming a clamp surrounding the E2. The U5BR interacts extensively with a region of UbcH5B that is distinct from both the active site and the RING-interacting region, referred to as the backside of the E2. An apparent paradox is that the high-affinity binding of the AO7 clamp to UbcH5B, which is dependent on the U5BR, decreases the rate of ubiquitination. We establish that this is a consequence of blocking the stimulatory, non-covalent, binding of ubiquitin to the backside of UbcH5B. Interestingly, when non-covalent backside ubiquitin binding cannot occur, the AO7 clamp now enhances the rate of ubiquitination. The high-affinity binding of the AO7 clamp to UbcH5B has also allowed for the co-crystallization of previously described and functionally important RING mutants at the RING-E2 interface. We show that mutations having marked effects on function only minimally affect the intermolecular interactions between the AO7 RING and UbcH5B, establishing a high degree of complexity in activation through the RING-E2 interface.


Bioinformatics approach to prioritize known drugs towards repurposing for tuberculosis.
New drugs are urgently needed to cure tuberculosis (TB) in a short period of time without causing any adverse effects since currently used drugs for the treatment of multi drug-resistant TB cause several adverse effects with poor success rate. Therefore, we aimed to prioritize known drugs towards repurposing for TB by employing bioinformatics approach in the present study. A total of 1554 FDA approved drugs were obtained from DrugBank. Serine/threonine-protein kinase, pknB (Rv0014c) of Mycobacterium tuberculosis (Mtb) was selected as the drug target since it involves in several vital functions of the Mtb. All of the 1554 drugs were subjected to molecular docking with pknB. Glide and AutoDock Vina were employed using rigid docking followed by induced fit docking protocol for prioritization of drugs. Out of 14 drugs prioritized, six are suggested as high-confident drugs towards repurposing for TB as they were consistently found within top 10 ranks of both methods, and strongly binding in the active site of the pknB. We also found atorvastatin as one of the high-confident drugs, which has already been demonstrated to be active against Mtb under in vitro conditions by other researchers. Therefore, we propose that the prioritized six high-confident drugs as potential candidates for repurposing for TB and suggest for further experimental studies. We also suggest that the bioinformatics procedure we have employed in this study could be effectively applied for prioritization of drugs for other diseases.


Magnetic relaxation switch detection of human chorionic gonadotrophin.
Functionalized nanoparticle contrast agents, also known as magnetic relaxation switches (MRS), were prepared to detect protein A and the beta subunit of human chorionic gonadotrophin (hCG-beta). Antibodies were attached to cross-linked iron oxide (CLIO) nanoparticles using standard peptide chemistry. Protein A was used as a simple model analyte, as it is naturally multivalent and can bind multiple CLIO-IgG simultaneously. The addition of PA to CLIO-IgG resulted in transverse relaxation time (T2) shortening compared to a blank control as seen by NMR relaxometry measurements. Analyte-induced aggregation was confirmed by light scattering particle size analysis. A two-particle system was designed to measure hCG-beta, as it is not multivalent and requires conjugation of a matched pair of monoclonal antibodies to CLIO (referred to as C95 and C97). Measurement of hCG-beta is important, as elevated serum levels are associated with malignancies including testicular and ovarian cancers. The addition of hCG-beta to C95 and C97 resulted in T2 shortening with a linear dynamic concentration range of 0.1 to 1 molecules of analyte per nanoparticle. Similar data were obtained for the hCG dimer. Observations with higher stoichiometric ratios of analyte to nanoparticle and increased nanoparticle valency were also made. This method can potentially be adapted to detect other biomarkers in solution.


Plasmid profile analysis as a tool for characterization of epidemic Shigella sonnei strains.
The usefulness of plasmid profile analysis as a marker to determine the strain number of Shigella sonnei implicated in an epidemic outbreak and its prevalency in our community was studied. We could define two multirresistant strains and determine that the drug resistance was plasmid mediated in both. One strain carried a tra- plasmid which encoded (Sm, Sd)r, the other one carried two tra+ plasmids which encoded (Ap-Cb, Sm, Sd)r and (Sm, Km-Nm, Sd, Tp)r respectively. These strains and some coisolates collected during the later phase of the outbreak carried cryptic plasmids which showed similar electrophoretic mobilities.


Infra Red Dye and Endostar Loaded Poly Lactic Acid Nano Particles as a Novel Theranostic Nanomedicine for Breast Cancer.
Endostar, a novel recombinant human endostatin, has been proven to inhibit tumor angiogenesis and is utilized as an anticancer drug. While free drugs can display limited efficacy, nanoscaled anticancer drugs have been fabricated and proven to possess superior therapeutic effects. Poly(lactic acid) (PLA) is a FDA-approved biomaterial displaying excellent biocompatibility and low toxicity. In this study, Endostar-loaded PLA nanoparticles (EPNPs) were first prepared, and a near-infrared (NIR) dye, IRDye 800CW, was conjugated to the surface for detecting nanoparticle biodistribution through fluorescence molecular imaging (FMI) using an orthotopic breast tumor mouse model. The antitumor efficacy of EPNPs was examined using bioluminescence imaging (BLI) and immunohistology. To further improve the antitumor effects, we combined EPNPs with zoledronic acid monohydrate (ZA), which is known to decrease the tumor-associated macrophages (TAM) and inhibit tumor progression. We found that EPNPs decreased human umbilical vein endothelial cell (HUVEC) viability by inhibiting tumor growth gene expression more significantly than free Endostar in vitro. In vivo, EPNPs displayed better tumor growth inhibitory effects compared with free Endostar, and the combination of EPNPs with ZA exhibited more significant antitumor effects. As confirmed by CD31 and CD11b immunohistochemistry, the combination of EPNPs and ZA showed synergistic effects in reducing tumor angiogenesis and TAM accumulation in tumor regions. Taken together, this study presents a novel and effective form of nanoscaled Endostar for the treatment of breast cancer that displays synergistic antitumor effects in combination with ZA.


Physician and Patient Radiation Exposure During Endovascular Procedures.
Endovascular procedures expose both patients and physicians to fluoroscopic ionizing radiation that carries a dose-dependent risk of acute toxicity and a small, but demonstrable, long-term risk of malignancy due to resultant genetic mutations. Exposure doses vary widely based upon patient-related factors including body size and anatomic complexity, operator technique, procedure type (diagnostic vs. therapeutic), vascular bed imaged, and imaging equipment employed. Effective dosage may vary as much as 200-fold for physicians and 20-fold for patients depending upon the procedure: for example, complex aortic interventions with branched graft devices may convey mean effective doses of more than 0.4 mSv for physicians and 100 mSv for patients, whereas distal, small-vessel angiography may entail mean effective doses of less than 0.002 mSv for physicians and 5 mSv for patients. Particular attention is given to physicians' ocular exposure, which may cause cataract development, and to hand exposure, which is significantly higher than total body exposure when operators work near the x-ray beam. Given the risks of radiation exposure, numerous strategies have been developed to reduce both physician and patient doses. These measures include physician education about dose-reducing imaging techniques, development of low-dose imaging equipment, introduction of new radiation shielding drapes and caps, and real-time dose monitoring. Here, we review physician and patient effective doses of radiation by procedure type as reported in the literature and present recent data regarding dose-reduction strategies.


Synthesis of indenes by the palladium-catalyzed carboannulation of internal alkynes.
[reaction: see text] A number of highly substituted indenes have been prepared in good yields by treating functionally substituted aryl halides with various internal alkynes in the presence of a palladium catalyst. The reaction is believed to proceed by regioselective arylpalladation of the alkyne and subsequent nucleophilic displacement of the palladium in the resulting vinylpalladium intermediate.


Patch-Wise Spatial-Temporal Quality Enhancement for HEVC Compressed Video.
Recently, many deep learning based researches are conducted to explore the potential quality improvement of compressed videos. These methods mostly utilize either the spatial or temporal information to perform frame-level video enhancement. However, they fail in combining different spatial-temporal information to adaptively utilize adjacent patches to enhance the current patch and achieve limited enhancement performance especially on scene-changing and strong-motion videos. To overcome these limitations, we propose a patch-wise spatial-temporal quality enhancement network which firstly extracts spatial and temporal features, then recalibrates and fuses the obtained spatial and temporal features. Specifically, we design a temporal and spatial-wise attention-based feature distillation structure to adaptively utilize the adjacent patches for distilling patch-wise temporal features. For adaptively enhancing different patch with spatial and temporal information, a channel and spatial-wise attention fusion block is proposed to achieve patch-wise recalibration and fusion of spatial and temporal features. Experimental results demonstrate our network achieves peak signal-to-noise ratio improvement, 0.55 - 0.69 dB compared with the compressed videos at different quantization parameters, outperforming state-of-the-art approach.


Involvement of nitric oxide in iodine deficiency-induced microvascular remodeling in the thyroid gland: role of nitric oxide synthase 3 and ryanodine receptors.
Iodine deficiency (ID) induces microvascular changes in the thyroid gland via a TSH-independent reactive oxygen species-hypoxia inducible factor (HIF)-1α-vascular endothelial growth factor (VEGF) pathway. The involvement of nitric oxide (NO) in this pathway and the role of calcium (Ca(2+)) and of ryanodine receptors (RYRs) in NO synthase 3 (NOS3) activation were investigated in a murine model of goitrogenesis and in 3 in vitro models of ID, including primary cultures of human thyrocytes. ID activated NOS3 and the production of NO in thyrocytes in vitro and increased the thyroid blood flow in vivo. Using bevacizumab (a blocking antibody against VEGF-A) in mice, it appeared that NOS3 is activated upstream of VEGF-A. L-nitroarginine methyl ester (a NOS inhibitor) blocked the ID-induced increase in thyroid blood flow in vivo and NO production in vitro, as well as ID-induced VEGF-A mRNA and HIF-1α expression in vitro, whereas S-nitroso-acetyl-penicillamine (a NO donor) did the opposite. Ca(2+) is involved in this pathway as intracellular Ca(2+) flux increased after ID, and thapsigargin activated NOS3 and increased VEGF-A mRNA expression. Two of the 3 known mammalian RYR isoforms (RYR1 and RYR2) were shown to be expressed in thyrocytes. RYR inhibition using ryanodine at 10μM decreased ID-induced NOS3 activation, HIF-1α, and VEGF-A expression, whereas RYR activation with ryanodine at 1nM increased NOS3 activation and VEGF-A mRNA expression. In conclusion, during the early phase of TSH-independent ID-induced microvascular activation, ID sequentially activates RYRs and NOS3, thereby supporting ID-induced activation of the NO/HIF-1α/VEGF-A pathway in thyrocytes.


What's in a name: what analyst and patient call each other.
Awkward moments often arise between patient and analyst involving the question, "What do we call each other?" The manner in which the dyad address each other contains material central to the patient's inner life. Names, like dreams, deserve a privileged status as providing a royal road into the paradoxical analytic relationship and the unconscious conflicts that feed it. Whether an analyst addresses the patient formally, informally, or not at all, awareness of the issues surrounding names is important.


Anomalous biased diffusion in a randomly layered medium.
We present analytical results for the biased diffusion of particles moving under a constant force in a randomly layered medium. The influence of this medium on the particle dynamics is modeled by a piecewise constant random force. The long-time behavior of the particle position is studied in the frame of a continuous-time random walk on a semi-infinite one-dimensional lattice. We formulate the conditions for anomalous diffusion, derive the diffusion laws, and analyze their dependence on the particle mass and the distribution of the random force.


Role of noncoding RNAs in pancreatic ductal adenocarcinoma associated cachexia.
Cachexia is an acute syndrome that is very commonly observed in patients with cancer. Cachexia is the number one cause of death in patients with metastatic disease and is also the major factor for physical toxicity and financial burden. More importantly, the majority of patients with advanced-stage pancreatic ductal adenocarcinoma (PDAC) cancer undergo cachexia. Pancreatic cancer causes deaths of ∼50,000 Americans and about 400,000 people worldwide every year. The high mortality rates in metastatic PDAC are due to systemic pathologies and cachexia, which quickens death in these patients. About 90% of all patients with PDAC undergo wasting of muscle causing mobility loss and leading to a number of additional pathological conditions. PDAC-associated cancer cachexia emanates from complex signaling cues involving both mechanical and biological signals. Tumor invasion is associated with the loss of pancreatic function-induced digestive disorders and malabsorption, which causes subsequent weight loss and eventually promotes cachexia. Besides, systemic inflammation of patients with PDAC could release chemical cues (e.g., cytokine-mediated Atrogin-1/MAFbx expression) that participate in muscle wasting. Our understanding of genes, proteins, and cytokines involved in promoting cancer cachexia has evolved considerably. However, the role of epigenetic factors, particularly the role of noncoding RNAs (ncRNAs) in regulating PDAC-associated cachexia is less studied. In this review article, the most updated knowledge on the various ncRNAs including microRNAs (miRs), long noncoding RNA (lncRNAs), piwi interacting RNAs (PiwiRNAs), small nucleolar RNA (snoRNAs), and circular RNAs (circRNA) and their roles in cancer cachexia are described.


Improving risk management systematically.
The management of risk is an ever more prevalent issue amongst healthcare professionals due to key changes in recent years driving visibility and transparency. Medical gases constitute an important area of risk--the gases are used, administered and handled by many different people and the chief executive is ultimately responsible. Such risks can be managed down by a hospital according to the letter and spirit of HTM 2022, EN737 and NMSR. The biggest failing of the current system where hospitals take it upon themselves to ensure compliance, is that typically little training is actually performed, there is almost no monitoring, and often people on the front line are unaware of the risks that they are running. A systematic response to managing risk is the only way forward, and a key decision a hospital needs to make is whether to persist towards this goal itself, or to involve a technical and clinical supplier. BOC Medical is in a key position to be of value.


Identification and validation of novel CSF biomarkers for early stages of Alzheimer's disease.
The pathology of Alzheimer's disease (AD) begins years prior to clinical diagnosis. The development of antecedent biomarkers that indicate the presence of AD pathology and predict risk for decline in both cognitively normal and mildly impaired individuals will be useful as effective therapies are developed. While cerebrospinal fluid (CSF) markers such as amyloid-β (Aβ) 42 and tau are useful, additional biomarkers are needed. To identify new markers, we utilized 2-D difference gel electrophoresis (2-D DIGE) of individual CSF samples from subjects with very mild AD versus controls after depletion of high-abundant proteins. Protein spots displaying differential abundance between the two groups were identified with MS. A number of candidate biomarkers were identified in 18 gel features. Selected candidates were quantified in a larger clinical set using ELISA. The mean levels of α1-antichymotrypsin (ACT), antithrombin III (ATIII), and zinc-α2-glycoprotein (ZAG) were significantly higher in the mild AD group, and the mean level of carnosinase 1 (CNDP1) was decreased. When these biomarkers are optimally combined, there is a strong trend toward greater specificity and sensitivity based on clinical diagnosis than when used individually. Our findings provide novel biomarker candidates for very mild and mild AD that can be further assessed as antecedent markers and predictors of clinical progression.


Time compression of visual perception around microsaccades.
Even during fixation, our eyes are in constant motion. For example, microsaccades are small (typically <1°) eye movements that occur 1~3 times/second. Despite their tiny and transient nature, our percept of visual space is compressed before microsaccades (Hafed ZM, Lovejoy LP, Krauzlis RJ. Eur J Neurosci 37: 1169-1181, 2013). As visual space and time are interconnected at both the physical and physiological levels, we asked whether microsaccades also affect the temporal aspects of visual perception. Here we demonstrate that the perceived interval between transient visual stimuli was compressed if accompanied by microsaccades. This temporal compression extended approximately ±200 ms from microsaccade occurrence, and depending on their particular pattern, multiple microsaccades further enhanced or counteracted this temporal compression. The compression of time surrounding microsaccades resembles that associated with more voluntary macrosaccades (Morrone MC, Ross J, Burr D. Nat Neurosci 8: 950-954, 2005). Our results suggest common neural processes underlying both saccade and microsaccade misperceptions, mediated, likely, through extraretinal mechanisms.NEW & NOTEWORTHY Here we show that humans perceive the duration of visual events as compressed if they are accompanied by microsaccades. Despite the tiny and transient nature of microsaccades, time compression extended more than ±200 ms from their occurrence. Moreover, the number, pattern, and temporal coincidence of microsaccades relative to visual events all contribute to this time misperception. Our results reveal a detailed picture of how our visual time percepts are altered by microsaccades.


Oxidation of hydrogen sulfide by flocculated Thiobaccillus denitrificans in a continuous culture.
In a continuous fermentation, significant advantages may be gained by immobilization of microbial cells. Immobilization allows cells to be retained in the fermenter or to be readily recovered and recycled. Therefore, the hydraulic retention time and the biomass retention time are decoupled. A novel cell immobilization has been developed for the immobilization of autotrophic bacteria by coculture with floc-forming heterotrophic bacteria with growth of the latter limited by the availability of organic carbon. The result is an immobilization matrix which grows along with the immobilized autotroph. We have previously demonstrated the utility of this approach by immobilizing the chemoautotroph Thiobacillus denitrificans in macroscopic floc by coculture with floc-forming heterotrophs from an activated sludge treatment facility. Floc with excellent settling characteristics were produced. These floc have now been used to remove H(2)S from a gas stream bubbled through continuous cultures. The stoichiometry and kinetics of H(2)S oxidation by immobilized T. denitrificans were comparable to that reported previously for free-cell cultures. Oxygen uptake measurements indicated the growth of both T. denitrificans and the heterotrophs although the medium contained no added organic carbon. Continuous cultures with total biomass recycle were maintained for up to four months indicating the long-term stability of the commensal relationship between the immobilized autotroph and the heterotrophs which composed the immobilization matrix. It was observed that at any given H(2)S loading the biomass concentration reached a maximum and leveled out. The ultimate biomass concentration was dependent upon the H(2)S feed rate.


Intracellular potential changes following coronary occlusion in isolated perfused rat hearts.
A method of perfusing rat ventricles has been developed which permits the recording of intracellular potentials from up to 10 cell layers below the endocardial surface. Intracellular potentials from all layers remained the same for up to 1.5 h before occlusion. Regional occlusion of flow was produced by occluding the left anterior descending coronary artery and then intracellular potentials were recorded from normal and occluded cells for up to 2 h after occlusion. Immediately after occlusion, marked changes in potentials were recorded from occluded tissue. The greatest change was in the duration of the action potential which showed a marked shortening. There was also a reduction in the maximum rise rate and action potential height with smaller falls in resting membrane potential. Changes were greatest in the deeper cells (layers 6-10) and least in superficial subendocardial cells which were always superfused with perfusion fluid. Occlusion increased the number of quiescent cells (no action potential) as well as the number of cells showing aberrant action potential configurations (e.g., double peaks). Similar changes in intracellular potentials following occlusion were also recorded from the subepicardial surface of anaesthetized rats in situ. Arrhythmias induced by occlusion were similar to those seen in conscious rats following occlusion of a coronary artery.


Large number of ultraconserved elements were already present in the jawed vertebrate ancestor.
Stephen (2008) identified 13,736 ultraconserved elements (UCEs) in placental mammals and investigated their evolution in opossum, chicken, frog, and fugu. They found that there was a massive expansion of UCEs during tetrapod evolution and the substitution rate in UCEs showed a significant decline in tetrapods compared with fugu, suggesting they were exapted in tetrapods. They considered it unlikely that these elements are ancient but evolved at a higher rate in teleost fishes. In this study, we investigated the evolution of UCEs in a cartilaginous fish, the elephant shark and show that nearly half the UCEs were present in the jawed vertebrate ancestor. The substitution rate in UCEs is higher in fugu than in elephant shark, and approximately one-third of ancient UCEs have diverged beyond recognition in teleost fishes. These data indicate that UCEs have evolved at a higher rate in teleost fishes, which may have implications for their vast diversity and evolutionary success.


Structure of Hsp33/YOR391Cp from the yeast Saccharomyces cerevisiae.
Saccharomyces cerevisiae Hsp33/YOR391Cp is a member of the ThiI/DJ-1/PfpI superfamily. Hsp33 was overexpressed in Escherichia coli and its crystal structure was determined at 2.40 Å resolution. Structural comparison revealed that Hsp33 adopts an α/β-hydrolase fold and possesses the putative Cys-His-Glu catalytic triad common to the Hsp31 family, suggesting that Hsp33 and Hsp31 share similar aminopeptidase activity, while structural deviations in helices α2-α3 of the core domain might be responsible for the access of different peptide substrates.


Sex Differences in Cognitive Flexibility and Resting Brain Networks in Middle-Aged Marmosets.
Sex differences in human cognitive performance are well characterized. However, the neural correlates of these differences remain elusive. This issue may be clarified using nonhuman primates, for which sociocultural influences are minimized. We used the marmoset (Callithrix jacchus) to investigate sex differences in two aspects of executive function: reversal learning and intradimensional/extradimensional (ID/ED) set shifting. Stress reactivity and motor function were also assessed. In agreement with human literature, females needed more trials than males to acquire the reversals. No sex differences in ED set shifting or motivational measures were observed. The findings suggest enhanced habit formation in females, perhaps due to striatal estrogenic effects. Both sexes showed increased urinary cortisol during social separation stressor, but females showed an earlier increase in cortisol and a greater increase in agitated locomotion, possibly indicating enhanced stress reactivity. Independent of sex, basal cortisol predicted cognitive performance. No sex differences were found in motor performance. Associations between brain networks and reversal learning performance were investigated using resting state fMRI. Resting state functional connectivity (rsFC) analyses revealed sex differences in cognitive networks, with differences in overall neural network metrics and specific regions, including the prefrontal cortex, caudate, putamen, and nucleus accumbens. Correlations between cognitive flexibility and neural connectivity indicate that sex differences in cognitive flexibility are related to sex-dependent patterns of resting brain networks. Overall, our findings reveal sex differences in reversal learning, brain networks, and their relationship in the marmoset, positioning this species as an excellent model to investigate the biological basis of cognitive sex differences.


A study of emotional intelligence and perceived parenting styles among adolescents in a rural area in Karnataka.
Adolescence is the time which is crucial for the overall development of a person both mentally and physically. In this period, along with academic intelligence, emotional intelligence (EI) also plays an equal or strong role in student life. This study was to assess EI, parental bonding, and their association among adolescents in high schools under Sarjapur PHC area. This was a cross-sectional study conducted among high school students under Sarjapur PHC area. The EI was assessed using EI scale which measured self-awareness, self-regulation, motivation, empathy, and social skills. The parental bonding instrument was utilized to determine the parental styles of both the parents and was interpreted in terms of care and protection as neglectful parenting, affectionless control, optimal parenting, and affectionate control. A total of 300 adolescents were interviewed. It was seen that most of them had low EI in self-awareness, i.e., 92 (30.7%), motivation 99 (33%), and social skills 101 (33.7%). It was also observed that most of them had high EI in self-regulation, i.e., 98 (32.7%) and moderately high EI in empathy 117 (39%). The study group perceived that 147 (49%) of the fathers and 109 (36.3%) of the mothers had affectionless control. Along with poor parenting, most of the respondents also have low EI in self-awareness, motivation, and social skills which has to be addressed for the future of the country.


Prosody recognition in adults with high-functioning autism spectrum disorders: from psychoacoustics to cognition.
Prosody is an important tool of human communication, carrying both affective and pragmatic messages in speech. Prosody recognition relies on processing of acoustic cues, such as the fundamental frequency of the voice signal, and their interpretation according to acquired socioemotional scripts. Individuals with autism spectrum disorders (ASD) show deficiencies in affective prosody recognition. These deficiencies have been mostly associated with general difficulties in emotion recognition. The current study explored an additional association between affective prosody recognition in ASD and auditory perceptual abilities. Twenty high-functioning male adults with ASD and 32 typically developing male adults, matched on age and verbal abilities undertook a battery of auditory tasks. These included affective and pragmatic prosody recognition tasks, two psychoacoustic tasks (pitch direction recognition and pitch discrimination), and a facial emotion recognition task, representing nonvocal emotion recognition. Compared with controls, the ASD group demonstrated poorer performance on both vocal and facial emotion recognition, but not on pragmatic prosody recognition or on any of the psychoacoustic tasks. Both groups showed strong associations between psychoacoustic abilities and prosody recognition, both affective and pragmatic, although these were more pronounced in the ASD group. Facial emotion recognition predicted vocal emotion recognition in the ASD group only. These findings suggest that auditory perceptual abilities, alongside general emotion recognition abilities, play a significant role in affective prosody recognition in ASD.


The general properties including accuracy and resolution of linear filtering methods for strain estimation.
The vast majority of strain imaging systems applies linear filtering to estimate strain from displacement data. Methods such as piecewise-linear least squares regression and staggered strain estimation have come to be widely known and applied, but the properties of these estimators have rarely (or never) been compared quantitatively. Given their tractable properties, careful analysis of linear filters allows us to make numerous observations that are simple, yet valuable. We consider accuracy and resolving power, which raises the question of whether any particular filter offers the best possible accuracy at a given resolution. Our surprising results provide insight at two levels: They highlight general considerations affecting the type of filter that is appropriate for practical applications, and indicate promising avenues for further research.


Synthesis, structure and properties of {M4O4} cubanes containing nickel(II) and cobalt(II).
A survey of the crystal structures containing simple {M4O4} cubane units is reported. It shows that the average M-M distance in these complexes is relatively constant for a given metal ion M. The structures are all distorted from the idealised cube to a T(d) structure, and most show a further distortion which, however, usually maintains some elements of symmetry. A system for classifying the different types of ligand in these complexes is proposed. Two new cubanes of cobalt(II) and nickel(II) with the ligand (R,R)-bis-1,2-(1-methylbenzimidazol-2-yl)ethane-1,2-diol, (R,R)- or its enantiomer have been isolated and the crystal structure of the cobalt(II) complex confirms the cubane structure. Electronic, CD and (1)H NMR spectra and magnetic susceptibility data are reported. The magnetic data for these and other compounds in the literature are discussed in terms of the structural parameters.


Surgical removal versus retention for the management of asymptomatic impacted wisdom teeth.
The prophylactic removal of asymptomatic impacted wisdom teeth is defined as the (surgical) removal of wisdom teeth in the absence of local disease. Impacted wisdom teeth may be associated with pathological changes, such as inflammation of the gums around the tooth, root resorption, gum and alveolar bone disease, damage to the adjacent teeth and the development of cysts and tumours. Other reasons to justify prophylactic removal have been to prevent late incisor crowding. When surgical removal is carried out in older patients, following the development of symptoms, the risk of postoperative complications, pain and discomfort increases. Nevertheless, in most developed countries prophylactic removal of trouble-free wisdom teeth, either impacted or fully erupted, has long been considered as 'appropriate care' and is a very common procedure. There is a need to determine whether there is evidence to support this practice. To evaluate the effects of prophylactic removal of asymptomatic impacted wisdom teeth in adolescents and adults compared with the retention (conservative management) of these wisdom teeth. The following electronic databases were searched: the Cochrane Oral Health Group's Trials Register (to 30 March 2012), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 1), MEDLINE via OVID (1950 to 30 March 2012), and EMBASE via OVID (1980 to 30 March 2012). There were no restrictions on language or date of publication. All randomised controlled trials (RCTs) on adolescents and adults comparing the effect of prophylactic removal of asymptomatic impacted wisdom teeth with no-treatment (retention). Six review authors screened the results of the search and assessed whether trials met the inclusion criteria for the review. Data extraction and risk of bias assessment were conducted in duplicate and independently by six review authors. Where information was unclear, authors of studies were contacted for additional information. No RCTs were identified that compared the removal of asymptomatic wisdom teeth with retention and reported quality of life. One RCT on adolescents was identified that compared the removal of impacted mandibular wisdom teeth with retention and only examined the effect on late lower incisor crowding. This study at high risk of bias provided no evidence that extraction of wisdom teeth had an effect on lower incisor crowding over 5 years. Insufficient evidence was found to support or refute routine prophylactic removal of asymptomatic impacted wisdom teeth in adults. A single trial comparing removal versus retention found no evidence of a difference on late lower incisor crowding at 5 years, however no other relevant outcomes were measured.Watchful monitoring of asymptomatic third molar teeth may be a more prudent strategy.


n-channel polymers by design: optimizing the interplay of solubilizing substituents, crystal packing, and field-effect transistor characteristics in polymeric bithiophene-imide semiconductors.
Electron transporting (n-channel) polymer semiconductors for field-effect transistors are rare. In this investigation, the synthesis and characterization of new electron-depleted N-alkyl-2,2'-bithiophene-3,3'-dicarboximide-based pi-conjugated homopolymers and copolymers containing the 2,2'-bithiophene unit are reported. A novel design approach is employed using computational modeling to identify favorable monomer properties such as core planarity, solubilizing substituent tailorability, and appropriate electron affinity with gratifying results. Monomeric model compounds are synthesized to confirm these properties, and a crystal structure reveals a short 3.43 A pi-pi stacking distance with favorable solubilizing substituent orientations. A family of 10 homopolymers and bithiophene copolymers is then synthesized via Yamamoto and Stille polymerizations, respectively. Two of these polymers are processable in common organic solvents: the homopolymer poly(N-(2-octyldodecyl)-2,2'-bithiophene-3,3'-dicarboximide) (P1) exhibits n-channel FET activity, and the copolymer poly(N-(2-octyldodecyl)-2,2':5',2'':5'',2'''-quaterthiophene-3,3'-dicarboximide) (P2) exhibits air-stable p-channel FET operation. After annealing, P1 films exhibit a very high degree of crystallinity and an electron mobility > 0.01 cm (2) V(-1) s(-1) with a current on-off ratio of 10 (7), which is remarkably independent of film-deposition conditions. Extraordinarily, P1 films also exhibit terracing in AFM images with a step height matching the X-ray diffraction d spacing, a rare phenomenon for polymeric organic semiconductors. Another fascinating property of these materials is the air-stable p-channel FET performance of annealed P2 films, which exhibit a hole mobility of approximately 0.01 cm(2) V(-1) s(-1) and a current on-off ratio of 10(7).


Connector inversion probe technology: a powerful one-primer multiplex DNA amplification system for numerous scientific applications.
We combined components of a previous assay referred to as Molecular Inversion Probe (MIP) with a complete gap filling strategy, creating a versatile powerful one-primer multiplex amplification system. As a proof-of-concept, this novel method, which employs a Connector Inversion Probe (CIPer), was tested as a genetic tool for pathogen diagnosis, typing, and antibiotic resistance screening with two distinct systems: i) a conserved sequence primer system for genotyping Human Papillomavirus (HPV), a cancer-associated viral agent and ii) screening for antibiotic resistance mutations in the bacterial pathogen Neisseria gonorrhoeae. We also discuss future applications and advances of the CIPer technology such as integration with digital amplification and next-generation sequencing methods. Furthermore, we introduce the concept of two-dimension informational barcodes, i.e. "multiplex multiplexing padlocks" (MMPs). For the readers' convenience, we also provide an on-line tutorial with user-interface software application CIP creator 1.0.1, for custom probe generation from virtually any new or established primer-pairs.


Wireless recording from unrestrained monkeys reveals motor goal encoding beyond immediate reach in frontoparietal cortex.
System neuroscience of motor cognition regarding the space beyond immediate reach mandates free, yet experimentally controlled movements. We present an experimental environment (Reach Cage) and a versatile visuo-haptic interaction system (MaCaQuE) for investigating goal-directed whole-body movements of unrestrained monkeys. Two rhesus monkeys conducted instructed walk-and-reach movements towards targets flexibly positioned in the cage. We tracked 3D multi-joint arm and head movements using markerless motion capture. Movements show small trial-to-trial variability despite being unrestrained. We wirelessly recorded 192 broad-band neural signals from three cortical sensorimotor areas simultaneously. Single unit activity is selective for different reach and walk-and-reach movements. Walk-and-reach targets could be decoded from premotor and parietal but not motor cortical activity during movement planning. The Reach Cage allows systems-level sensorimotor neuroscience studies with full-body movements in a configurable 3D spatial setting with unrestrained monkeys. We conclude that the primate frontoparietal network encodes reach goals beyond immediate reach during movement planning.


Tolvaptan for the treatment of hyponatremia and hypervolemia in patients with congestive heart failure.
Patients with heart failure often show increased arginine vasopressin secretion and enhanced sympathetic and renin-angiotensin-aldosterone activation, which accelerate renal water reabsorption, causing water retention and volume overload. Tolvaptan is an orally active antagonist of arginine vasopressin type 2 receptors in the collecting duct of the kidney that inhibits water reabsorption without substantially affecting the electrolyte balance. Tolvaptan in combination with conventional diuretics improves fluid retention and congestive symptoms in patients with heart failure and volume overload, with minimal effects on hemodynamics and serum potassium. Tolvaptan slightly increases serum sodium concentrations, generally within the normal range. Although it does not seem to affect long-term mortality, tolvaptan does improve short-term water retention and congestive symptoms in heart failure patients with volume overload despite the use of conventional diuretics, and is approved for this indication in Japan.


Diffuse muscular coactivation (DMC) as a potential source of pain in fibromyalgia -- part 1.
Fibromyalgia is characterized by diffuse pain, the origin of which remains obscure. This study explored a phenomenon labeled Diffuse Muscle Coactivation (DMC) as a possible source of pain in fibromyalgia. DMC is defined as an increase from resting levels (tonus) in the electrical activity of any muscle during a movement which does not involve that muscle and is not part of the agonist-antagonist unit. When compared to controls this activity in persons with fibromyalgia was 1.75 times more prevalent and demonstrated significantly higher peak amplitudes. Possible neurological mechanisms are discussed.


Enantioselective discrimination of alcohols by hydrogen bonding: a SERS study.
Efficient and generic enantioselective discrimination of various chiral alcohols is achieved by using surface-enhanced Raman scattering (SERS) spectroscopy through charge-transfer (CT) contributions. The relative intensities of the peaks in the SERS spectra of a chiral selector are strongly dependent on the chirality of its surroundings. This highly distinct spectral discrepancy may be due to the tendency of chiral isomers to form intermolecular hydrogen-bonding complexes with the chiral selector in different molecular orientations, resulting in different CT states and SERS intensities of the adsorbates in the system. This study opens a new avenue leading to the development of novel enantiosensing strategies. A particular advantage of this approach is that it is label-free and does not employ any chiral reagents, including chiral light.


Defect Regulating of Few-Layer Antimonene from Acid-Assisted Exfoliation for Enhanced Electrocatalytic Nitrogen Fixation.
Nitrogen reduction reaction (NRR), as a green and sustainable technology, is far from a practical application due to the lack of efficient electrocatalysts. In this work, we found that antimonene, a group-VA elemental two-dimensional (2D) material, is attractive as an electrocatalyst for NRR. The antimonene here is acquired through chemical exfoliation of antimony (Sb) using H2SO4 for the first time, which simultaneously achieved efficient large-sized exfoliation and created a high density of active edge sites. Moreover, the concentration of defects shows a gradual increasing tendency as the treatment time extends. The obtained antimonene exhibited favorable average ammonia (NH3) yield and Faradaic efficiency as high as 2.08 μg h-1 cm-2 and 14.25% at -0.7 V versus RHE, respectively. Density functional theory calculations prove that the sufficient exposure of edge defects is favorable for reducing the reaction barrier and strengthening the interaction between antimonene and the intermediates of NRR, thus increasing the selectivity and yield rate of NH3. The chemical exfoliation of Sb reported here offers an alternative avenue to engineer the surface structures of group-VA elemental-based catalysts. Investigation of NRR using 2D antimonene can further provide deep insight into the mechanism and principle of NRR over group-VA elemental nanosheets.


Assessment of the effect of Enteromorpha prolifera on bacterial community structures in aquaculture environment.
In recent years, Enteromorpha prolifera blooms had serious impacts on costal environments and fisheries in China. Nevertheless, the effects of E. prolifera on microbial ecology remain unknown. In this study, for the first time, an Illumina sequencing analysis was used to investigate bacterial communities in source water, aquaculture ponds with E. prolifera, and an aquaculture pond in which E. prolifera -free. Principal coordinate and phylogenic analyses revealed obvious differences among the bacterial communities in the pond water with and without E. prolifera. Abundant bacterial taxa in the E. prolifera-containing pond were generally absent from the pond without E. prolifera. Interestingly, pond water with E. prolifera was dominated by Actinomycetales (> 50%), as well as by anaerobic bacteria in the underlying sediment (Desulfobacterales and Desulfuromonadales (> 20%). Pond water in which E. prolifera-free was dominated by Rhodobacterales (58.19%), as well as aerobic and facultative anaerobic bacteria in the sediment. In addition, the ecological functions of other dominant bacteria, such as Candidatus Aquiluna, Microcella spp., and Marivita spp., should be studied in depth. Overall, massive growth of E. prolifera will have serious effects on bacterial communities, and, thus, it will have an important impact on the environment. The novel findings in this study will be valuable for understanding green tides.


Development of the orpheus perfusion simulator for use in high-fidelity extracorporeal membrane oxygenation simulation.
Despite its life-sustaining potential, extracorporeal membrane oxygenation (ECMO) remains a complex treatment modality for which close teamwork is imperative with a high risk of adverse events leading to significant morbidity and mortality. The provision of adequate training and continuing education is key in mitigating these risks. Traditional training for ECMO has relied predominantly on didactic education and hands-on water drills. These methods may overemphasize cognitive skills while underemphasizing technical skills and completely ignoring team and human factor skills. These water drills are often static, lacking the time pressure, typical alarms, and a sense of urgency inherent to actual critical ECMO scenarios. Simulation-based training provides an opportunity for staff to develop and maintain technical proficiency in high-risk, infrequent events without fear of harming patients. In addition, it provides opportunities for interdisciplinary training and improved communication and teamwork among team members (1). Although simulation has become widely accepted for training of practitioners from many disciplines, there are currently, to our knowledge, no commercially available dedicated high-fidelity ECMO simulators. Our article describes the modification of the Orpheus Perfusion Simulator and its incorporation into a fully immersive, high-fidelity, point-of-care ECMO simulation model.


Acute P38-Mediated Enhancement of P2X3 Receptor Currents by TNF-α in Rat Dorsal Root Ganglion Neurons.
Tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine and involves in a variety of pain conditions. Some findings suggest that TNF-α may act directly on primary afferent neurons to induce acute pain hypersensitivity through non-transcriptional regulation. This study investigated whether TNF-α had an effect on functional activity of P2X3 receptors in primary sensory neurons. Herein, we report that a brief (5 min) application of TNF-α rapidly enhanced the electrophysiological activity of P2X3 receptors in rat dorsal root ganglia (DRG) neurons. Electrophysiological recordings were carried out on rat DRG neurons, and nociceptive behavior was quantified in rats. A brief (5 min) exposure of TNF-α rapidly increased P2X3 receptor-mediated and α,β-methylene-ATP (α,β-meATP)-evoked inward currents in a dose-dependent manner. The potentiation of P2X3 receptor-mediated ATP currents by TNF-α was voltage-independent. TNF-α shifted the concentration-response curve for α,β-meATP upwards, with an increase of 31.57 ± 6.81% in the maximal current response to α,β-meATP. This acute potentiation of ATP currents by TNF-α was blocked by p38 mitogen-activated protein kinase (MAPK) inhibitor SB202190, but not by non-selective cyclooxygenase inhibitor indomethacin, suggesting involvement of p38 MAPK, but not cyclooxygenase. Moreover, intraplantar injection of TNF-α and α,β-meATP produced a synergistic effect on mechanical allodynia in rats. TNF-α-induced mechanical allodynia was also alleviated after local P2X3 receptors were blocked. These results suggested that TNF-α rapidly sensitized P2X3 receptors in primary sensory neurons via a p38 MAPK dependent pathway, which revealed a novel peripheral mechanism underlying acute mechanical hypersensitivity by peripheral administration of TNF-α.


Visualization of the initiation and sequential expansion of the metamorphic conversion of anuran larval skin into the precursor of adult type.
A tadpole of bullfrog, Rana catesbeiana, is originally covered with the larval skin over its entire body. Drastic changes arise in both the epidermis and the subcutaneous connective tissue at an early developmental stage, producing the precursor of adult type skin (pre-adult skin). It was found that calcium is a useful probe to detect the region where the precursor formation has occurred because its deposition in the upper part of subcutaneous collagen bundles coincides with the appearance of the pre-adult skin. Whole-mount in situ staining of tadpoles with alizarin red S revealed the initiation site of the premetamorphic transformation of the larval skin into the adult precursor and its ensuing region-dependent expansion. The pre-adult skin first emerged at TK II to III (TK, Taylor and Kollros staging) t lateral sides of the body, which led us to postulate that 'the center for premetamorphic skin transformation' is formed at the specific site in this region. This center moved dorsally and then ventrally, then reached to the most proximal region of the tail, yielding a unique sequential conversion pattern by around TK V when the conversion was completed in the trunk. The present study also visualized the process of the hindlimb skin transformation.


Early pregnancy termination with mifepristone and misoprostol in the United States.
Mifepristone and a prostaglandin have been used successfully to terminate pregnancy in Europe and China. We report the results of a large U.S. study of mifepristone and misoprostol in women with pregnancies of up to nine weeks' duration. We administered 600 mg of mifepristone and then 400 microg of misoprostol two days later to 2121 women seeking termination of their pregnancies at 17 centers. The women were observed for four hours after the administration of misoprostol and returned on day 15 for final assessment. Two thousand fifteen women completed the final assessment. Among them, pregnancy was terminated in 762 of the 827 women pregnant for < or =49 days (92 percent), 563 of the 678 women pregnant for 50 to 56 days (83 percent), and 395 of the 510 women pregnant for 57 to 63 days (77 percent) (P<0.001). Termination occurred within 4 hours after the administration of misoprostol in 49 percent of the women and within 24 hours in 75 percent. Failures, defined as cases requiring surgical intervention for medical reasons or because the patient requested it, the abortion was incomplete, or the pregnancy was ongoing, increased with increasing duration of pregnancy. The largest increase was in failures representing ongoing pregnancy, which increased from 1 percent in the < or =49-days group to 9 percent in the 57-to-63-days group (P<0.001). Abdominal pain, nausea, vomiting, diarrhea, and vaginal bleeding also increased with advancing gestational age. Two percent of the women in the < or =49-days group, as compared with 4 percent in each of the other two groups, were hospitalized, underwent surgical interventions, and received intravenous fluids (P=0.008). This mifepristone-misoprostol regimen is effective in terminating pregnancies, especially in women with pregnancies of 49 days' duration or less.


[ABH and Lewis antigens of tracheal glands. II. Lewis negative individuals].
Immunocytochemical studies were performed on tracheal wall samples embedded in paraffin; the samples were taken at 23 autopsies. In all cases, the red cells had been typed in postmortem serological studies as being Le(a-b-). Blood-group antigens were demonstrated by the indirect immunoperoxidase technique, using monoclonal Anti-A, Anti-B, Anti-Lea and Anti-Leb; H was detected by UEA 1. The secretor characteristics could clearly be diagnosed from the ABH staining pattern of the mucous glands. In 11 cases, the lewis antigen labeling patterns were identical to the group of Lewis-positive individuals. It seems probable, from the statistical point of view, that these 11 individuals were, in fact, Lewis-positive and that the negative serology resulted from deterioration of the cadaver blood samples. The immunocytochemistry was quite different in the remaining 12 cases: (a) secretors (n = 9) were completely negative for Lea, Leb was equally negative in one case, but in the remainder it was detectable within mucous epithelia in minimal amounts and in an atypical granular distribution; (b) nonsecretors (n = 3) reversely exhibited complete negativity for Leb but a minimal staining for Lea. These findings are in harmony with the well established Lewis serology typing of secretions in Lewis negative individuals. Thus, a minimal Lewis antigen biosynthesis and secretion seem to occur in the absence of the Le gene: A alpha-4-L-fucosyltransferase of low activity might be the product of the allele le.


[Holmium laser enucleation versus open prostatectomy for large volume benign prostatic hyperplasia: a meta-analysis of the therapeutic effect and safety].
To compare holmium laser enucleation (HoLEP) versus open prostatectomy (OP) for large volume benign prostatic hyperplasia. The randomized controlled trials (RCTs) pertaining to HoLEP and OP for management of large volume benign prostatic hyperplasia were retrieved from Medline and Embase. Meta-analysis was performed using Review Manager 5.0 software. Three RCTs were included in the analysis. No significant differences were found in IPSS or Qmax between HoLEP and OP (P>0.05). Compared with OP, HoLEP was associated with significantly less blood loss, a shorter catheterization time and a shorter hospital stay, but a longer operating time. HoLEP and OP were similar in terms of urethral stricture, stress incontinence, transfusion requirement and the rate of reintervention. HoLEP and OP have similar therapeutic effects in the management of large volume benign prostatic hyperplasia. Although with a longer operating time and less resected tissue, HoLEP causes less blood loss and requires a shorter catheterization time and a shorter hospital stay. HoLEP has a comparable safety to OP in terms of the adverse events.


A Hyperandrogenic Environment Causes Intrinsic Defects That Are Detrimental to Follicular Dynamics in a PCOS Mouse Model.
Polycystic ovary syndrome (PCOS) is a common cause of female infertility. Hyperandrogenism is both a major symptom and key diagnostic trait of PCOS; however, the direct impact of this androgen excess on ovarian dynamics is unclear. By combining a DHT-induced PCOS mouse model with an ex vivo follicle culture system, we investigated the impact of hyperandrogenism on ovarian function. Ovaries from PCOS mice exhibited the characteristic polycystic ovary morphology with numerous large cystic follicles and no corpora lutea present. Isolation and individual culture of preantral and antral follicles from PCOS mice resulted in slower growth rates during 5 days compared with the follicles isolated from control mice (P < 0.01). In contrast, preovulatory follicles from PCOS mice exhibited a significant increase in growth rate compared with controls (P < 0.01). Preantral follicles from PCOS ovaries maintained comparable follicular health as control follicles, but antral and preovulatory PCOS follicles exhibited reduced follicle health (P < 0.01) and survival rates (P < 0.01). Compared with controls, PCOS females also exhibited a poorer response to hyperstimulation (P < 0.01), impaired oocyte function evident by increased levels of reactive oxygen species (P < 0.01), and a reduction in on-time embryo development (P < 0.01). These results demonstrate that prolonged exposure to androgen excess leads to aberrant follicle development, which persists even after removal from the hyperandrogenic environment, causing perturbed follicular developmental trajectories. These findings indicate that an in vivo hyperandrogenic environment in patients with PCOS may intrinsically induce detrimental effects on follicles and oocytes.


Cooperative binding of initiator protein to replication origin conferred by single amino acid substitution.
The replication initiator protein pi of plasmid R6K binds seven 22 bp direct repeats (DR) in the gamma origin. The pi protein also binds to an inverted repeat (IR) in the operator of its own gene, pir, which lies outside the gamma origin sequences. A genetic system was devised to select for pi protein mutants which discriminate between IR and DR (York et al., Gene (Amst.) 116, 7-12, 1992; York and Filutowicz, J. Biol. Chem. 268, 21854-21861, 1993). From this selection the mutant pi S87N protein was isolated which is deficient in repressing the pir gene's expression because it cannot bind to IR at the pir gene operator. Remarkably, we discovered that pi S87N binds to DR cooperatively under conditions where wt pi binds independently. Moreover, the pi S87N is more active as a replication initiator in vivo when supplied at the same level as wt pi. Quantitative binding assays showed that both wt pi and pi S87N bind a DNA fragment containing a single DR unit with a similar affinity (Kd = 0.3 x 10(-12) M). Thus, cooperativity of pi S87N is most likely achieved through altered interactions between promoters bound at adjacent DR units.


Structure-property relationships in an iridium(III) bis(terpyridine) complex with extended conjugated side chains.
Iridium(III) bis(terpyridine) complexes are known as excellent triplet emitters with emission lifetimes in the order of microseconds. We report the homoleptic complex [IrL2](3+) (L = 4'-(4-2,5-bis(octyloxy)-4-styrylphenyl)ethinyl)phenyl)-2,2':6',2″-terpyridine) that shows no detectable phosphorescence at room temperature but shows fluorescence. Emission spectra of [IrL2](3+) depend on the excitation wavelength. The origin of this behavior is studied with the help of results from (TD-)DFT calculations and is attributed to the selective excitation of different rotamers and isomers. Femtosecond-transient absorption experiments give further support for this interpretation as the specific excited-state absorption features of Z- and E-stilbene motives can be identified.


High-luminosity visible and near-IR Fourier-transform photoacoustic spectrometer.
A visible and near-infrared (0.36-3-microm) Michelson interferometer has been built to perform Fourier transform photoacoustic spectroscopy. The scanning (step and integrate) and the internal modulation are obtained with only one active element: the moving mirror holder driven by a linear motor. The signal-to-improvement and the performance of the spectrometer are compared with other photoacoustic methods and illustrated by various spectra.


Altered Decision-Making under Risk in Obesity.
The negative consequences of energy dense foods are well known, yet people increasingly make unhealthy food choices leading to obesity (i.e., risky decisions). The aims of this study were: [1] to compare performance in decision-making tasks under risk and under ambiguity between individuals with obesity, overweight and normal weight; [2] to examine the associations between body mass index (BMI) and decision-making, and the degree to which these associations are modulated by reward sensitivity. Seventy-nine adults were recruited and classified in three groups according to their BMI: obesity, overweight and normal-weight. Groups were similar in terms of age, education and socio-economic status, and were screened for comorbid medical and mental health conditions. Decision-making under risk was measured via the Wheel of Fortune Task (WoFT) and decision-making under ambiguity via the Iowa Gambling Task (IGT). Reward sensitivity was indicated by the Sensitivity to Punishment and Sensitivity to Reward Questionnaire (SPSRQ). Individuals with obesity made riskier choices in the WoFT, specifically in choices with an expected value close to zero and in the propensity to risk index. No differences were found in IGT performance or SPSRQ scores. BMI was associated with risk-taking (WoFT performance), independently of reward sensitivity. Obesity is linked to a propensity to make risky decisions in experimental conditions analogous to everyday food choices.


Cold Fusion: Massive Karyotype Evolution in the Antarctic Bullhead Notothen Notothenia coriiceps.
Half of all vertebrate species share a series of chromosome fusions that preceded the teleost genome duplication (TGD), but we do not understand the causative evolutionary mechanisms. The "Robertsonian-translocation hypothesis" suggests a regular fusion of each ancestral acro- or telocentric chromosome to just one other by centromere fusions, thus halving the karyotype. An alternative "genome-stirring hypothesis" posits haphazard and repeated fusions, inversions, and reciprocal and nonreciprocal translocations. To study large-scale karyotype reduction, we investigated the decrease of chromosome numbers in Antarctic notothenioid fish. Most notothenioids have 24 haploid chromosomes, but bullhead notothen (Notothenia coriiceps) has 11. To understand mechanisms, we made a RAD-tag meiotic map with ∼10,000 polymorphic markers. Comparative genomics aligned about a thousand orthologs of platyfish and stickleback genes along bullhead chromosomes. Results revealed that 9 of 11 bullhead chromosomes arose by fusion of just two ancestral chromosomes and two others by fusion of three ancestral chromosomes. All markers from each ancestral chromosome remained contiguous, implying no inversions across fusion borders. Karyotype comparisons support a history of: (1) Robertsonian fusions of 22 ancestral chromosomes in pairs to yield 11 fused plus two small unfused chromosomes, like N. angustata; (2) fusion of one of the remaining two ancestral chromosomes to a preexisting fused pair, giving 12 chromosomes like N. rossii; and (3) fusion of the remaining ancestral chromosome to another fused pair, giving 11 chromosomes in N. coriiceps These results raise the question of what selective forces promoted the systematic fusion of chromosomes in pairs and the suppression of pericentric inversions in this lineage, and provide a model for chromosome fusions in stem teleosts.


Safe threshold of capillary blood glucose for predicting early future neonatal hypoglycaemia in babies born to mothers with gestational diabetes mellitus, an observational, retrospective cohort study.
There is increasing pressure to get women and babies home rapidly after birth. Babies born to mothers with gestational diabetes mellitus (GDM) currently get 24-h inpatient monitoring. We investigated whether a low-risk group of babies born to mothers with GDM could be defined for shorter inpatient hypoglycaemia monitoring. Observational, retrospective cohort study conducted in a tertiary maternity hospital in 2018. Singleton, term babies born to women with GDM and no other risk factors for hypoglycaemia, were included. Capillary blood glucose (BG) testing and clinical observations for signs of hypoglycaemia during the first 24-h after birth. BG was checked in all babies before the second feed. Subsequent testing occurred if the first result was < 2.0 mmol/L, or clinical suspicion developed for hypoglycaemia. Neonatal hypoglycaemia, defined as either capillary or venous glucose ≤ 2.0 mmol/L and/or clinical signs of neonatal hypoglycaemia requiring oral or intravenous dextrose (lethargy, abnormal feeding behaviour or seizures). Fifteen of 106 babies developed hypoglycaemia within the first 24-h. Maternal and neonatal characteristics were not predictive. All babies with hypoglycaemia had an initial capillary BG ≤ 2.6 mmol/L (Area under the ROC curve (AUC) 0.96, 95% Confidence Interval (CI) 0.91-1.0). This result was validated on a further 65 babies, of whom 10 developed hypoglycaemia, in the first 24-h of life. Using the 2.6 mmol/L threshold, extended monitoring as an inpatient could have been avoided for 60% of babies in this study. Whilst prospective validation is needed, this approach could help tailor postnatal care plans for babies born to mothers with GDM.


Sleep Quality in Psoriasis Patients and its Relations with Possible Affecting Factors.
Psoriasis (PS) is a chronic, immune-mediated inflammatory skin disease. PS may lead to significant effects on health-related quality of life (HRQoL) and other outcomes. In the present study, an investigation into sleep quality (SQ), and its possible relations with factors which may affect SQ were aimed. A total of 74 subjects from both sexes were enrolled in this study, between January and July 2017. Patients were evaluated with their demographics, body mass index (BMI), Psoriasis Area Severity Index (PASI), Pittsburgh Sleep Quality Index (PSQI), Psoriasis Quality of Life Index (PQLI), Self Perception Scale (SPS). Additionally, accompanying chronic diseases, disease duration and severity of pruritus were recorded. Obtained PSQI values were compared with the mentioned parameters concerning the significance of their relations with it. SPSS version 24, 2016 was used to analyse the data, and significance was evaluated with p-values of <0.05, 0.01, and 0.001, and rho (r) values of <0.2, =0.2-0.4, =0.4-0.6, =0.6-0.8 and >0.8. Thirty-seven female and 37 male were studied. The mean age of total of the study population was 47.21±13.91. Mean BMI and mean duration were 30.09± 4.68 kg/m2, and 10.58±9.1 months. Mean values of PASI, PSQI, SPS, and PQLI of the study group were 19.79±16.99, 9.14±5.09, 142.12±23.83, and 21.94±16.31, respectively. Approximately thirty-one percent of them had at least one chronic disease. Alcohol and smoking rates were 17.56%, 50%. PASI was positive/strongly correlated with PQLI and negative/weakly correlated with SPS. No correlation was detected between PSQI values and age, gender, BMI, and SPS values. PSQI was moderately correlated with PQLI, diabetes mellitus (DM), and pruritus severity, whereas it was weak correlated with PASI, hypertension (HT), thyroid diseases and disease duration. PASI and DM showed a predictive effect on SQ. SQ is affected by certain factors, such as QoL, disease severity, disease duration, pruritus severity, accompanying disorders, such as HT, DM and thyroid diseases, in which disease severity and DM have predictive effects on SQ in PS patients. Controls of disease activation and prevention of progression in DM may provide to keep SQ in PS.


Perception of imposed leg length inequality in normal subjects.
Lower limb length differences of up to 10mm exist in 60% - 95% of the population.There are usually no symptoms or functional effects. Following Total Hip Arthroplasty (THA), satisfactory clinical results can be spoiled by dissatisfaction due to a change in leg length. Although the change in leg length may be modest in comparison to the normal variation, the patient may perceive this as a leg length discrepancy. To study the average threshold for perception, artificial leg length discrepancies of 5 mm to 25 mm were created in 30 young healthy adults using calibrated wooden blocks. Responses were recorded and analysed using a chi-squared test for independence and an independent measures t-test. Awareness of leg length discrepancy was related to the magnitude of the discrepancy (X2 (15)= 156.6, p<0.05 on the right side, and X2 (15)= 178.725 p<0.05 on the left side). It was shown that no subject reported a 5mm increase in leg length to be uncomfortable while all subjects were aware of leg length discrepancies of 20 mm and 25 mm. When there was a discrepancy of 10 mm in either lower limb, 29 out of 30 subjects (96.7%) thought there was a difference in leg length. Consequently it is suggested that during total hip arthroplasty the surgeon should aim for a leg length discrepancy of less than 10 mm.


Experimental approach for bacteriophage susceptibility testing of planktonic and sessile bacterial populations - Study protocol.
Antimicrobial resistance is a growing threat for all clinical branches. This phenomenon poses important challenges in controlling infectious diseases. However, multidrug resistance is not the only issue, as bacteria that are otherwise susceptible to common antibiotics express other patterns for evading antibiotherapy, for example they can aggregate within a self-produced matrix to form biofilm. We intend to perform a prospective laboratory study of the germs isolated from different samples collected from patients admitted with infectious pathology in reference hospitals in Romania. We will perform antibiotic resistance testing as well as phage testing, both on solid and liquid growth medium, for Staphylococcus spp., Enterococcus spp., and Pseudomonas spp. We intend to collect data for 150 patients with different infections with these identified pathogens. Phage susceptibility testing will be performed using 5 types of strain-specific bacteriophage mixtures: PYO, INTESTI, STAPHYLOCOCCAL (Eliava BioPreparations, Tbilisi, Georgia), PHAGYO, PHAGESTI (JSC "Biochimpharm", Tbilisi, Georgia). For phage-susceptible strains, we will evaluate biofilm formation in the presence of phages, as well as phage effect on already formed biofilm. Through this study, we intend to provide the first set of results on bacteriophage-susceptibility of bacteria isolated from patients with hard to treat infections, from reference hospitals in Romania. By evaluating a large number of bacterial strains we aim to predict and project biofilm kinetics, while adding binary phage dilutions at key timepoints during biofilm formation. POSDRU/159/1.5/S/141531; Carol Davila University of Medicine and Pharmacy, Young Researchers Grant no. 28341/2013.


Reversible uremic deafness: is it correlated with the degree of anemia?
Hearing loss is a common finding in patients with end-stage renal failure. Uremic toxins, ototoxins, and axonal uremic neuropathy appear to be likely pathogenic factors. We analyzed whether an improvement in hearing capacity can be achieved with an improvement of anemia by erythropoietin (EPO) administration. Fifty patients on long-term hemodialysis in a single center were examined audiologically by otoscopy, tympanometry, pure tone audiometry, and the short increment sensitivity index. Twenty-five patients were treated with EPO in a dose of 120 U/kg per week over a period of 5 to 8 months, and the remaining 25 patients were not treated with EPO (controls). Both groups were reexamined audiologically after the study period, and the results were compared. In the group treated with EPO, the hemoglobin level increased from 7 +/- 0.9 to 11 +/- 0.8 g/dL, as against the control group, whose hemoglobin increased from 7.1 +/- 0.9 to 8 +/- g/dL. The audiologic tests were repeated at the end of the study period, and a significant improvement of hearing was found in the patients treated with EPO as compared with the control group (p < .001). Our study suggests that improvement of anemia in patients on long-term hemodialysis by administration of EPO is associated with an improvement in hearing capacity in a significant number of patients. Thus, anemia seems to be an important factor responsible for hearing disorders in patients with end-stage renal failure. Studies with larger numbers of patients are required to confirm this observation.


[2 cases of lymphangioleiomyomatosis treated by hormonal manipulation].
The course of disease in two women with bioptically verified lymphangioleiomyomatosis (LAM) is demonstrated. One was oestrogen- and progesterone-receptor negative, but responded promptly to hysterosalpingo-oophorectomy and has had no symptoms later. The other was receptor positive, but in spite of hysterosalpingo-oophorectomy and hormonal manipulation with tamoxifen and medroxyprogesterone, has had a complicated course of the disease with symptoms for ten years. LAM is a hormone dependent disease, but our knowledge is still incomplete. Hormonal manipulation should be tried in receptor positive as well as negative patients. Tamoxifen seems to have deleterious effects on the course of disease.


Identification and mutagenesis of the adeno-associated virus 5 sialic acid binding region.
As a genus, the dependoviruses use a diverse group of cell surface carbohydrates for attachment and entry. Despite the fact that a majority of adeno-associated viruses (AAVs) utilize sialic acid (SIA) for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, two SIA binding regions were mapped for AAV5. The first site mapped to the depression in the center of the 3-fold axis of symmetry, while the second site was located under the βHI loop close to the 5-fold axis. Mutagenesis of amino acids 569 and 585 or 587 within the 3-fold depression resulted in elimination or alteration in SIA-dependent transduction, respectively. This change in SIA binding was confirmed using glycan microarrays. Mutagenesis of the second site identified a role in transduction that was SIA independent. Further studies of the mutants at the 3-fold site demonstrated a change in transduction activity and cell tropism in vivo as well as resistance to neutralization by a polyclonal antibody raised against the wild-type virus. Despite the fact that a majority of AAVs utilize sialic acid for binding and transduction, this virus-carbohydrate interaction is poorly understood. Utilizing X-ray crystallography, the sialic acid binding regions of AAV5 were identified and studied using a variety of approaches. Mutagenesis of this region resulted in elimination or alteration in sialic acid-dependent transduction in cell lines. This change in sialic acid glycan binding was confirmed using glycan arrays. Further study also demonstrated a change in transduction and activity and cell tropism in vivo as well as resistance to neutralization by antibodies raised against the wild-type virus.


The complete dorsal structure is formed from only the blastocoel roof of Xenopus blastula: insight into the gastrulation movement evolutionarily conserved among chordates.
Gastrulation is a critical event whose molecular mechanisms are thought to be conserved among vertebrates. However, the morphological movement during gastrulation appears to be divergent across species, making it difficult to discuss the evolution of the process. Previously, we proposed a novel amphibian gastrulation model, the "subduction and zippering (S&Z) model". In this model, the organizer and the prospective neuroectoderm are originally localized in the blastula's blastocoel roof, and these embryonic regions move downward to make physical contact of their inner surfaces with each other at the dorsal marginal zone. The developmental stage when contact between the head organizer and the anterior-most neuroectoderm is established is called "anterior contact establishment (ACE)." After ACE, the A-P body axis elongates posteriorly. According to this model, the body axis is derived from limited regions of the dorsal marginal zone at ACE. To investigate this possibility, we conducted stepwise tissue deletions using Xenopus laevis embryos and revealed that the dorsal one-third of the marginal zone had the ability to form the complete dorsal structure by itself. Furthermore, a blastocoel roof explant of the blastula, which should contain the organizer and the prospective neuroectoderm in the S&Z model, autonomously underwent gastrulation and formed the complete dorsal structure. Collectively, these results are consistent with the S&Z gastrulation model and identify the embryonic region sufficient for construction of the complete dorsal structure. Finally, by comparing amphibian gastrulation to gastrulation of protochordates and amniotes, we discuss the gastrulation movement evolutionarily conserved among chordates.


The demographic impact of Partition in the Punjab in 1947.
We use data from the 1931, 1941, and 1951 censuses of India and the 1951 census of Pakistan to examine the demographic consequences of Partition in the Punjab in 1947. Had growth rates for the period 1931-41 for the Punjab as a whole continued to 1951, the population of the Punjab would have been 2.9 million larger than that recorded in 1951. Population losses from migration and mortality above age 20 were approximately 2.7 million greater between 1941 and 1951 than would have been predicted by loss rates between 1931 and 1941. We estimate a net Partition-related population movement out of the combined Punjab of about 400,000. We conclude from several lines of analysis that Partition-related population losses in the Punjab, either from deaths or unrecorded migration, were in the range 2.3-3.2 million. Partition was also marked by a dramatic religious homogenization at the district level.


Investigating the association between vitamin D dietary intake during pregnancy and incidence of clubfoot in neonates.
Talipes equinovarus (clubfoot) is a congenital lower foot deformity that results from a neuromuscular deficiency, but the precise etiology remains elusive. Vitamin D is important for fetal neuromuscular development. In this study, we investigated the association between dietary vitamin D intake during pregnancy and incidence of clubfoot in neonates, since such a question has thus far been overlooked. We conducted a secondary analysis of data collected in the United States, between 2007 and 2011 for a case-control study of children born with clubfoot. Participating mothers were interviewed by telephone about dietary and other health and life-style indicators. Exposure to vitamin D was recorded as the average daily intake of dietary vitamin D over a period of 6 months before pregnancy began. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression. The dataset included 2667 study participants, of which 663 were cases. Logistic regression showed no significant association between dietary vitamin D or log10 (Vitamin D) intake during pregnancy and incidence of clubfoot in neonates (OR = 1.00, CI = 1.00-1.00, OR = 1.51, CI = 0.83-2.82, respectively). No interaction in the regression model was found between vitamin D and other predictor variables. Results were not confounded by supplement intake of vitamin D during pregnancy. Results show no evidence of an association between dietary vitamin D intake and incidence of clubfoot in neonates. The lack of association is not confounded by consumption of vitamin D supplements during pregnancy.


A novel single-nucleotide substitution, Glu 4 Lys, in the leukotriene C4 synthase gene associated with allergic diseases.
Cysteinyl leukotrienes (cysLTs) play important roles in bronchial asthma, and can mediate bronchial smooth muscle constriction and increase mucous secretion, vascular permeability and cellular infiltration. We identified a novel heterozygous single-nucleotide substitution 10G>A (Glu 4 Lys) in the first exon of the leukotriene C4 synthase gene (LTC4S). This substitution was detected in 5 of 141 allergic patients, but not in 110 nonallergic subjects. There was a difference in the Glu 4 Lys frequency between the allergic patients and nonallergic subjects (Fisher's exact test, p=0.0460). The five patients with Glu 4 Lys had allergic diseases such as bronchial asthma and/or allergic dermatitis. Furthermore, a familial analysis of Glu 4 Lys revealed a link with allergic diseases. Thus, our results suggest that Glu 4 Lys in the LTC4S might be associated with allergic diseases.


["Very slow" cholangiography in hyperbilirubinemias and in chronic liver diseases].
The "ultra-slow" method for cholangiography in serious icterus due to chronic heptopathy is described. The results are related to different icterus stages. A comparison is drawn between this and conventional methods for examination of the bile ducts, assuming equal degrees of blood bilirubin.


Autophosphorylation of calcium/calmodulin-dependent protein kinase (CCaMK) at S343 or S344 generates an intramolecular interaction blocking the CaM-binding.
The Ca2+ and Ca2+/calmodulin-dependent protein kinase (CCaMK) is an important effector protein of Ca2+/calmodulin-mediated signaling, and in legumes, it is a critical regulator of plant-rhizobia and mycorrhizal symbioses. CCaMK contains a kinase domain, a calmodulin-binding/autoinhibitory domain and a visinin-like domain. Previous studies revealed the presence of 2 phosphorylation sites, S343 and S344, in the calmodulin-binding domain. Mutations at these sites affected the kinase activity and downstream rhizobium and mycorrhizal symbioses, which highlighted the importance of these residues in regulating protein activity. This addendum further clarifies the regulation of CCaMK by identifying an intramolecular interaction between residue(s) in the kinase domain and phosphorylation sites S343 and S344. This interaction turns off the substrate phosphorylation capacity of CCaMK.


The road toward human gene therapy--a 25-year perspective.
The concept of human gene therapy arose in the early 1970s and has now been the subject of many clinical trials in human patients. To date, there have been no truly convincing therapeutic successes, but any disappointment with that fact is due more to the exaggerated levels of our expectations than to any failure of concept. The concept of human gene therapy has been a startling success and it is now one of the most important driving forces in medicine. Current tools have simply not been adequate for the difficult job of efficient and stable gene delivery, faithful and regulated gene expression and clinical correction of a human disease. Nevertheless, progress toward human gene therapy is rapid and inexorable and the second phase of human gene therapy, the implementation phase, will soon also succeed.


Tryptase activates phosphatidylinositol 3-kinases proteolytically independently from proteinase-activated receptor-2 in cultured dog airway smooth muscle cells.
Mast cell tryptase is a potent mitogen for many cells in the airways and lung, but the cellular mechanisms for its growth stimulatory effects are poorly understood. Our major goal was to determine whether tryptase activates phosphatidylinositol 3-kinases (PI 3-kinases) in cultured dog tracheal smooth muscle cells to induce its mitogenic effects. After exposure to tryptase, cells were lysed. Immunocomplexes prepared from the lysates using an antibody to the p85 subunit of PI 3-kinase, but not using anti-phosphotyrosine antibodies, possessed increased capacity to phosphorylate inositol on its D3 hydroxyl group. Tryptase also increased phosphorylation of Akt, a downstream target of PI 3-kinases. This effect was abolished by one PI 3-kinase inhibitor, wortmannin, and attenuated by another, LY-294004, which also blocked tryptase's mitogenic effects. Treatment of tryptase with p-amidino phenylmethanesulfonyl fluoride, to abolish its proteolytic activity irreversibly, inhibited its stimulatory effects on Akt phosphorylation. Proteinase-activated receptor-2 (PAR-2)-activating peptides failed to increase Akt phosphorylation in cultured dog tracheal smooth muscle cells, but the PAR-2-activating peptides did induce brisk increases in Akt phosphorylation in Madin-Darby canine kidney cells. We concluded that tryptase activates PI 3-kinases in cultured dog tracheal smooth muscle cells to induce its potent mitogenic effects. These effects of tryptase on PI 3-kinases appear to occur via novel proteolytic mechanisms independent from PAR-2. Also, tryptase, although comparable in mitogenic potency to platelet-derived growth factor (PDGF), induces considerably less tyrosine phosphorylation on proteins than occur in response to PDGF.


Substrate regulation of monoamine oxidases.
The rate of oxidation by monoamine oxidase (MAO) of a particular amine in a given cell depends on the levels of MAO-A and MAO-B expressed in the mitochondrial outer membranes, on the amine concentration and the oxygen concentration. Its disposal will be slowed by the presence of competing amines or endogenous inhibitors. However, substrate binding alters the properties of MAO and influences catalytic turnover. (a) It increases the redox potential of the flavin making possible the transfer of electrons from the higher potential amine. (b) It accelerates the reactivity of the covalently bound flavin with oxygen, effectively increasing the Vm (particularly for MAO-B). (c) It bypasses the generation of free oxidised enzyme in the reaction cycle so that, at high amine concentrations, only the affinity of a substrate or inhibitor for the reduced enzyme (particularly for MAO-A) is important. These changes are induced only by substrate, not by the few stable products available nor by inhibitors suggesting a very specific interaction between a substrate ligand and the enzyme. The altered properties are very different for MAO-A and MAO-B even with the same substrate. Elucidation of the mechanisms involved must await structural information from physical studies, molecular modelling and mutational analysis.


A new species of Pupulina van Beneden, 1892 (Copepoda, Siphonostomatoida, Caligidae) from Aetobatuscf.narinari (Pisces, Myliobatidae) from the Pacific coast of Ecuador.
A new caligid copepod species, Pupulinamantensissp. n. is described based on female and male specimens collected from the gills of the myliobatid elasmobranch Aetobatuscf.narinari Euphrasen, 1790 captured off the Pacific coast of Ecuador. The new species has a unique combination of characters that diverges from its known congeners, including: (i) weakly developed posterolateral processes on the genital complex; (ii) large spines on posterior surface of maxilliped basis (iii) abdomen slender, unsegmented, approximately 1/2 length and 1/5 width of genital complex; (iv) third exopodal segment of leg II with single long naked spine adjacent to minute, naked lateral spine; (v) velum of leg II with adjacent patch of denticles; (vi) caudal rami slightly less than half the length of genital complex; (vii) post-antennal process with robust, posteriorly directed tine, sclerotized stump posterolaterally, and two multi-sensillate papillae located on or near base of process (viii) post-oral process oval. The overall prevalence of P.mantensissp. n. on its host was 37.5% and its mean abundance was 1.87 specimens per host. This is the second record of the genus Pupulina from Ecuador and the second record of Pupulina infecting rays of the Myliobatinae genus Aetobatus, of the subfamily Myliobatinae, after its discovery on A.ocellatus in Australia, thus confirming this expansion of its previously known host range to a new elasmobranch subfamily.


Factors associated with adenoma detection rate and diagnosis of polyps and colorectal cancer during colonoscopy in France: results of a prospective, nationwide survey.
Colonoscopy can prevent deaths due to colorectal cancer (CRC) through early diagnosis or resection of colonic adenomas. We conducted a prospective, nationwide study on colonoscopy practice in France. An online questionnaire was administered to 2,600 French gastroenterologists. Data from all consecutive colonoscopies performed during one week were collected. A statistical extrapolation of the results to a whole year was performed, and factors potentially associated with the adenoma detection rate (ADR) or the diagnosis of polyps or cancer were assessed. A total of 342 gastroenterologists, representative of the overall population of French gastroenterologists, provided data on 3,266 colonoscopies, corresponding to 1,200,529 (95% CI: 1,125,936-1,275,122) procedures for the year 2011. The indication for colonoscopy was CRC screening and digestive symptoms in 49.6% and 38.9% of cases, respectively. Polypectomy was performed in 35.5% of cases. The ADR and prevalence of CRC were 17.7% and 2.9%, respectively. The main factors associated with a high ADR were male gender (p=0.0001), age over 50 (p=0.0001), personal or family history of CRC or colorectal polyps (p<0.0001 and p<0.0001, respectively), and positive fecal occult blood test (p=0.0005). The prevalence of CRC was three times higher in patients with their first colonoscopy (4.2% vs. 1.4%; p<0.0001). For the first time in France, we report nationwide prospective data on colonoscopy practice, including histological results. We found an average ADR of 17.7%, and observed reduced CRC incidence in patients with previous colonoscopy.


A 16-Week Home-Based Progressive Resistance Tube Training Among Older Adults With Type-2 Diabetes Mellitus: Effect on Glycemic Control.
Research has proven that aerobic exercise improves glucose homeostasis among patients with type 2 diabetes mellitus (T2DM). Elastic resistance (tube or band) is suggested as a good alternative for home-based strength training among older adults including those with T2DM due to its low cost, simplicity, portability, and versatility. This study aimed to measure the effects of 16-week home-based progressive resistance training (PRT), using a resistance tube on glucose homeostasis and cardiovascular risk factors among older adults with T2DM. A total of 70 participants aged 61.68 (5.50) years with T2DM were assigned to the intervention (n = 35) and control (n = 35) groups in this quasi-experimental trial. The intervention group underwent 16 weeks of home-based PRT using a resistance tube. Significant improvements in HbA1c (-1.34% point, p < 0.001), fasting blood glucose (-1.30 mmol/L, p < 0.001), and systolic blood pressure (-1.42 mmHg, p < 0.05) were observed after 16 weeks of intervention. However, no significant changes were observed in lipid profile, diastolic blood pressure, resting heart rate, and ankle-brachial index. The finding suggests that 16 weeks of home-based PRT using a resistance tube has the potential to improve glycemic control and reduce systolic blood pressure among older adults with T2DM and caused no adverse events.


Lower nucleus accumbens α-synuclein load and D3 receptor levels in Parkinson's disease with impulsive compulsive behaviours.
Impulsive compulsive behaviours in Parkinson's disease have been linked to increased dopaminergic release in the ventral striatum and excessive stimulation of dopamine D3 receptors. Thirty-one patients with impulsive compulsive behaviours and Parkinson's disease who donated their brains to the Queen Square Brain Bank for Neurological Disorders were assessed for α-synuclein neuropathological load and tyrosine hydroxylase levels in the nucleus accumbens, dorsal putamen and caudate using immunohistochemistry. Dopamine D2 and dopamine D3 receptors protein levels in the nucleus accumbens, frontal cortex and putamen were determined using western blotting. Results were compared to 29 Parkinson's disease cases without impulsive compulsive behaviours matched by age, sex, disease duration, age at Parkinson's disease onset and disease duration. The majority of patients with impulsive compulsive behaviours had dopamine dysregulation syndrome. Patients with Parkinson's disease and impulsive compulsive behaviours had lower α-synuclein load and dopamine D3 receptor levels in the nucleus accumbens. No differences were seen between groups in the other brain areas and in the analysis of tyrosine hydroxylase and dopamine D2 receptor levels. Lower α-synuclein load in the nucleus accumbens of individuals with Parkinson's disease and impulsive compulsive behaviours was confirmed on western blotting. Downregulation of the dopamine D3 receptor levels may have occurred either as a consequence of the degenerative process or of a pre-morbid trait. The lower levels of α-synuclein may have contributed to an excessive stimulation of the ventral striatum resulting in impulsive compulsive behaviours.


Mobilization-based engraftment of haematopoietic stem cells: a new perspective for chemotherapy-free gene therapy and transplantation.
In haematopoietic stem cell transplantation (HSCT), haematopoietic stem cells (HSCs) from a healthy donor replace the patient's ones. Ex vivo HSC gene therapy (HSC-GT) is a form of HSCT in which HSCs, usually from an autologous source, are genetically modified before infusion, to generate a progeny of gene-modified cells. In HSCT and HSC-GT, chemotherapy is administered before infusion to free space in the bone marrow (BM) niche, which is required for the engraftment of infused cells. Here, we review alternative chemotherapy-free approaches to niche voidance that could replace conventional regimens and alleviate the morbidity of the procedure. Literature was reviewed from PubMed-listed peer-reviewed articles. No new data are presented in this article. Chemotherapy exerts short and long-term toxicity to haematopoietic and non-haematopoietic organs. Whenever chemotherapy is solely used to allow engraftment of donor HSCs, rather than eliminating malignant cells, as in the case of HSC-GT for inborn genetic diseases, non-genotoxic approaches sparing off-target tissues are highly desirable. In principle, HSCs can be temporarily moved from the BM niches using mobilizing drugs or selectively cleared with targeted antibodies or immunotoxins to make space for the infused cells. However, translation of these principles into clinically relevant settings is only at the beginning, and whether therapeutically meaningful levels of chimerism can be safely established with these approaches remains to be determined. In pre-clinical models, mobilization of HSCs from the niche can be tailored to accommodate the exchange and engraftment of infused cells. Infused cells can be further endowed with a transient engraftment advantage. Inter-individual efficiency and kinetics of HSC mobilization need to be carefully assessed. Investigations in large animal models of emerging non-genotoxic approaches will further strengthen the rationale and encourage application to the treatment of selected diseases.


The imperative for scientific societies to change the face of academia: Recommendations for immediate action.
As organizations that facilitate collaboration and communication, scientific societies have an opportunity, and a responsibility, to drive inclusion, diversity, equity, and accessibility in science in academia. The American Association for Anatomy (AAA), with its expressed and practiced culture of engagement, can serve as a model of best practice for other professional associations working to become more inclusive of individuals from historically underrepresented groups. In this publication, we acknowledge anatomy's exclusionary past, describe the present face of science in academia, and provide recommendations for societies, including the AAA, to accelerate change in academia. We are advocating for scientific societies to investigate inequities and revise practices for inclusivity; develop and empower underrepresented minority leadership; and commit resources in a sustained manner as an investment in underrepresented scientists who bring diverse perspectives and lived experiences to science in academia.


Spontaneous Bacterial Peritonitis in a Patient With Nonportal Hypertensive Ascites.
Background: Spontaneous bacterial peritonitis (SBP) is a life-threatening condition classically found as a complication of cirrhotic ascites, but it has rarely been documented in a case of nonportal hypertensive ascites. Case Report: We report the case of a 54-year-old male with SBP arising from nonportal hypertensive ascites in the setting of end-stage renal disease and restrictive cardiomyopathy, both secondary to primary amyloidosis (AL type, kappa light chain). Peritoneal fluid analysis showed a serum-ascites albumin gradient of 1.1 g/dL and total fluid protein of 3.6 g/dL consistent with nonportal hypertensive etiology. The patient was managed empirically with intravenous ceftriaxone and intravenous albumin. Additional workup was nondiagnostic for other causes of ascites, and the patient was discharged after a 7-day hospital course. Conclusion: Patients presenting with refractory ascites in the setting of end-stage renal disease, cardiomyopathy, and long-standing immunosuppressive therapy may be at increased risk for SBP despite a high ascitic fluid protein.


The pitfalls of planning for demographic change.
As we begin to understand the biology of aging, it will be ever more tempting to try to plan for the social consequences of the coming biomedical interventions in this arena. However, this will remain a daunting task, because the larger consequences of the arrival of antiaging interventions will greatly depend on the relative character and timing of the specific procedures that emerge. Three basic classes of interventions are likely: ones that slow aging in adults, ones that reverse aging in adults, and embryonic interventions that modify the overall trajectory of human aging. The consequences of each will differ significantly in the time required before noticeable demographic shifts begin to manifest in the human population, and in the social and political changes the interventions evoke. The specific societal consequences generally will arrive long before the demographic ones, and will hinge on the technical details of the interventions themselves--their complexity, physiological targets, modes of delivery, costs, unpleasantness, and the character and frequency of side effects.