Awareness, Attitude and Barriers Towards Evidence Based Dental Practice Amongst Practicing Dentists of Bhopal City.
Evidence based dental practice is said to be the recent best approach to provide treatments or interventions, methodically proven to be safe and sound, efficient and cost effective. So, for providing quality dental care, clinical expertise, research evidence and patient's preferences all should be given equal importance. To assess the awareness, attitude & barriers of evidence-based dental practice (EBDP) amongst dentists of Bhopal city. The target population of this cross-sectional study involves dentists of Bhopal city. Two hundred fifty private dentists of Bhopal were selected using convenience sampling technique. Data was collected using a self-administered questionnaire containing 15 questions for assessing Knowledge, attitude, practice & barriers in Evidence based practice. Chi-square, t-test & one-way ANOVA were applied for data analysis and p<0.05 was considered statistically significant. The study revealed that dental practitioners had low knowledge about evidence based dental practices but they showed positive attitude towards adopting it in their future practice. There exist certain barriers in practice of evidence based dentistry. Including evidence based dental practice teaching in dental curriculum may prove to be a significant step in effective and efficient dental care delivery to the patients. Barriers in evidence based practice needs to be identified & eliminated.


Para-hyoid ectopic parathyroid adenoma localized by Tc-99m MIBI SPECT.
A 64-year-old woman with a history of I-131 ablation for Graves hyperthyroidism and bilateral parathyroid exploration with resection of a left inferior parathyroid adenoma presented 2 years after surgery with marked fatigue, irritability, and joint pain. Laboratory testing revealed an elevated calcium and parathyroid hormone levels suspicious for hyperparathyroidism. The ultrasound indicated no evidence of a parathyroid adenoma. Tc-99m-MIBI SPECT demonstrated a focus of uptake posteroinferior to the right submandibular gland, suspicious for a parathyroid adenoma. Repeat ultrasound and CT confirmed the presence of a para-hyoid adenoma inferior to the right submandibular gland.


Achieving Remarkable Activity and Durability toward Oxygen Reduction Reaction Based on Ultrathin Rh-Doped Pt Nanowires.
The research of active and sustainable electrocatalysts toward oxygen reduction reaction (ORR) is of great importance for industrial application of fuel cells. Here, we report a remarkable ORR catalyst with both excellent mass activity and durability based on sub 2 nm thick Rh-doped Pt nanowires, which combine the merits of high utilization efficiency of Pt atoms, anisotropic one-dimensional nanostructure, and doping of Rh atoms. Compared with commercial Pt/C catalyst, the Rh-doped Pt nanowires/C catalyst shows a 7.8 and 5.4-fold enhancement in mass activity and specific activity, respectively. The combination of extended X-ray absorption fine structure analysis and density functional theory calculations reveals that the compressive strain and ligand effect in Rh-doped Pt nanowires optimize the adsorption energy of hydroxyl and in turn enhance the specific activity. Moreover, even after 10000 cycles of accelerated durability test in O2 condition, the Rh-doped Pt nanowires/C catalyst exhibits a drop of 9.2% in mass activity, against a big decrease of 72.3% for commercial Pt/C. The improved durability can be rationalized by the increased vacancy formation energy of Pt atoms for Rh-doped Pt nanowires.


Evidence that the citizenship mandate curtailed participation in Oregon's Medicaid family planning program.
The 2005 federal Deficit Reduction Act made proof of citizenship a requirement for Medicaid eligibility. We examined the effects on visits to Oregon's Medicaid family planning services eighteen months after the citizenship requirement was implemented. We analyzed 425,381 records of visits that occurred between May 2005 and April 2008 and found that, compared to the eighteen-month period before the mandate went into effect, visits declined by 33 percent. We conclude that Medicaid citizenship documentation requirements have been burdensome for Oregon Family Planning Expansion Project patients and costly for health care providers, reducing access to family planning and preventive measures and increasing the strain on the safety net.


Bendavia restores mitochondrial energy metabolism gene expression and suppresses cardiac fibrosis in the border zone of the infarcted heart.
We have observed that Bendavia, a mitochondrial-targeting peptide that binds the phospholipid cardiolipin and stabilizes the components of electron transport and ATP generation, improves cardiac function and prevents left ventricular remodeling in a 6week rat myocardial infarction (MI) model. We hypothesized that Bendavia restores mitochondrial biogenesis and gene expression, suppresses cardiac fibrosis, and preserves sarco/endoplasmic reticulum (SERCA2a) level in the noninfarcted border zone of infarcted hearts. Starting 2h after left coronary artery ligation, rats were randomized to receive Bendavia (3mg/kg/day), water or sham operation. At 6weeks, PCR array and qRT-PCR was performed to detect gene expression. Picrosirius red staining was used to analyze collagen deposition. There was decreased expression of 70 out of 84 genes related to mitochondrial energy metabolism in the border zone of untreated hearts. This down-regulation was largely reversed by Bendavia treatment. Downregulated mitochondrial biogenesis and glucose & fatty acid (FA) oxidation related genes were restored by administration of Bendavia. Matrix metalloproteinase (MMP9) and tissue inhibitor of metalloproteinase (TIMP1) gene expression were significantly increased in the border zone of untreated hearts. Bendavia completely prevented up-regulation of MMP9, but maintained TIMP1 gene expression. Picrosirius red staining demonstrated that Bendavia suppressed collagen deposition within border zone. In addition, Bendavia showed a trend toward restoring SERCA2a expression. Bendavia restored expression of mitochondrial energy metabolism related genes, prevented myocardial matrix remodeling and preserved SERCA2a expression in the noninfarcted border, which may have contributed to the preservation of cardiac structure and function.


Pancreatic Beta Cell Identity in Humans and the Role of Type 2 Diabetes.
Pancreatic beta cells uniquely synthetize, store, and release insulin. Specific molecular, functional as well as ultrastructural traits characterize their insulin secretion properties and survival phentoype. In this review we focus on human islet/beta cells, and describe the changes that occur in type 2 diabetes and could play roles in the disease as well as represent possible targets for therapeutical interventions. These include transcription factors, molecules involved in glucose metabolism and insulin granule handling. Quantitative and qualitative insulin release patterns and their changes in type 2 diabetes are also associated with ultrastructural features involving the insulin granules, the mitochondria, and the endoplasmic reticulum.


[Clinical studies on the measurement of urinary tissue polypeptide antigen (TPA) levels using Prolifigen TPA kit "Daiichi"-II in urothelial cancers].
We have investigated the clinical significance of urinary tissue polypeptide antigen (TPA) as a tumor marker for urothelial cancers. Urinary TPA levels were determined by the immunoradiometric assay of Prolifigen TPA Kit "Daiichi"-II in 486 healthy controls and 1835 patients with various diseases including 526 with urothelial cancers and 140 with prostatic cancer. The mean value of urinary TPA was 199 +/- 213 (1SD)U/1 in 486 healthy controls. 95% of them having a level below 600 U/l. Therefore, 600 U/l was applied as a cut-off level. Positive rates of urothelial cancers and reactivated prostatic cancer were 57.6% (148 of 248 cases) and 45.5% (5 of 11 cases) respectively. On the other hand, the false positive rate of most urological benign diseases was only about 20% except for the acute stage of urinary tract infections and upper urinary tract stones with hydronephrosis. There was no significant difference in the positive rate between urinary TPA level and urinary cytology in urothelial cancers. The combination of both tests raised the positive rate to 73.1%. Therefore, urinary TPA may be useful in the monitoring of urothelial cancers, and the combination of urinary TPA and urinary cytology may increase the diagnostic accuracy.


Characterization of a site-directed mutant of cytochrome b5 designed to alter axial imidazole ligand plane orientation.
Mutants of cytochrome b5 were designed to achieve reorientation of individual axial imidazole ligands. The orientation of the axial ligand planes is thought to modulate the reduction potential of bis(imidazole) axially ligated heme proteins. The A67V mutation achieved this goal through the substitution of a bulkier, hydrophobic ligand for a residue, in the sterically hindered hydrophobic heme binding pocket. Solution structures of mutant and wild-type proteins in the region of the mutation were calculated using restraints obtained from 1H and 15N 2D homonuclear and heteronuclear NMR spectra and 1H-15N 3D heteronuclear NMR spectra. More than 10 restraints per residue were used in the refinement of both structures. Average local rmsd for 20 refined structures was 0.30 A for the wild-type structure and 0.38 A for the A67V mutant. The transfer of amide proton resonance assignments from wild-type to the mutant protein was achieved through overlays of 15N-1H heteronuclear correlation spectra of the reduced proteins. Side chain assignments and sequential assignments were established using conventional assignment strategies. Calculation of the orientation of the components of the anisotropic paramagnetic susceptibility tensor, using methods similar to procedures applied to the wild-type protein, shows that the orientation of the in-plane components are identical in the wild-type and mutant proteins. However, the orientation of the z-component of the susceptibility tensor calculated for the mutant protein differs by 17 degrees for the A-form and by 11 degrees for the B-form from the orientation calculated for the wild-type protein. The rotation of the z-component of the susceptibility tensor (toward the delta meso proton) is in the same direction and is of the same magnitude as the rotation of the H63 imidazole ring induced by mutation.


A survey of scientific literacy to provide a foundation for designing science communication in Japan.
There are various definitions and survey methods for scientific literacy. Taking into consideration the contemporary significance of scientific literacy, we have defined it with an emphasis on its social aspects. To acquire the insights needed to design a form of science communication that will enhance the scientific literacy of each individual, we conducted a large-scale random survey within Japan of individuals older than 18 years, using a printed questionnaire. The data thus acquired were analyzed using factor analysis and cluster analysis to create a 3-factor/4-cluster model of people's interest and attitude toward science, technology and society and their resulting tendencies. Differences were found among the four clusters in terms of the three factors: scientific factor, social factor, and science-appreciating factor. We propose a plan for designing a form of science communication that is appropriate to this current status of scientific literacy in Japan.


Cytokine signal regulation and autoimmune disorders.
Understanding of biological activities of cytokines and exquisite mechanism to regulate their functions has facilitated the therapeutic concept to restore the disequilibrium between pro-inflammatory cytokines and anti-inflammatory cytokines or cytokine inhibitors in some autoimmune inflammatory diseases such as rheumatoid arthritis (RA) and Crohn's disease. The application of molecular biology techniques to design monoclonal antibodies, soluble receptors, or receptor antagonists as therapeutic biologic agents made it possible to regulate the cytokine signals for the treatment of the diseases refractory to conventional therapies. Japanese researchers have contributed considerably to the establishment of cytokine signal regulation in autoimmune diseases. In this article, Japanese studies of cytokine signal regulation, particularly for Interleukin-6 (IL-6) in autoimmune diseases are reviewed.


Variable expression of human lactoferrin gene in mice milk driven by its 90 KB upstream flanking sequences.
One major drawback in research of animal mammary gland bioreactors is the low production rate of high-expressing transgenic animals due to position effects. To obtain high and stable expression of foreign gene, yeast and bacterial artificial chromosome have been used as transgene vector in recent research. Human lactoferrin is a bioactive, versatile protein, and has large potential in nutritional and therapeutic applications. Therefore, production of recombinant lactoferrin using animal bioreactors was studied widely to satisfy its large requirement. We reported here a transgenic mice model with high-level expression of recombinant human lactoferrin in mammary gland. Transgene construct used here was a human bacterial artificial chromosome containing intact lactoferrin-encoding transcript unit, approximately 90 kb 5'-flanking sequences and 27.2 kb 3'-flanking sequences. We obtained totally 10 transgenic mice whereas two of them lacked of part of upstream sequences of the gene. Milk of eight transgenic mice line was detected by Western blot and radioimmunoassay and seven lines expressed recombinant human lactoferrin at high but variable level (0.29, 0.53, 0.90, 1.23, 2.76, 3.58, and 8.02 mg/mL, respectively). The variability of expression indicates that even the 90 kb 5' flanking sequence of the transgene can't overcome position effects completely. Moreover, we also determined sequences of 9.3 kb regulatory region and 10.6 kb encoding region of the gene and thus supplemented all unknown sequences. Our results suggested that transgene vector used here has potential to be used in large farm animals for production of recombinant human lactoferrin in industrial scale.


Dimerization choice and alternative functions of ZBTB transcription factors.
Zinc Finger DNA-binding domain-containing proteins are the most populous family among eukaryotic transcription factors. Among these, members of the BTB domain-containing ZBTB sub-family are mostly known for their transcriptional repressive functions. In this Viewpoint article, we explore molecular mechanisms that potentially diversify the function of ZBTB proteins based on their homo and heterodimerization, alternative splicing and post-translational modifications. We describe how the BTB domain is as much a scaffold for the assembly of co-repressors, as a domain that regulates protein stability. We highlight another mechanism that regulates ZBTB protein stability: phosphorylation in the zinc finger domain. We explore the non-transcriptional, structural roles of ZBTB proteins and highlight novel findings that describe the ability of ZBTB proteins to associate with poly adenosine ribose in the nucleus during the DNA damage response. Herein, we discuss the contribution of BTB domain scaffolds to the formation of transcriptional repressive complexes, to chromosome compartmentalization and their non-transcriptional, purely structural functions in the nucleus.


Medication maintenance of mentally ill patients by a pharmacist in a community setting.
The use of a community pharmacy as a facility for medication maintenance services usually provided by a mental health center was evaluated. The project pharmacist was affiliated with the community mental health center, the community pharmacy facility was borrowed for purposes of this study. Records and prepackaged medication were transported by the pharmacy-clinic. Medication histories were taken and maintained by the pharmacist. Problems such as medication noncompliance, drug side effects, drug interactions and minor alterations in the patients mental status were handled by the pharmacist. Telephone consultations with a psychiatrist were also available. Twenty-two patients were involved in the study over an eight-month period. The evaluation consisted of a patient acceptance questionnaire and a retrospective chart review analyzing the clinical response of patients. Data suggest that selected stabilized psychiatric patients can be safely maintained in the community pharmacy. A carefully structured program and a pharmacist with special competencies are felt to be prerequisites for this type of service.


LncRNA HOTAIR alleviates rheumatoid arthritis by targeting miR-138 and inactivating NF-κB pathway.
Rheumatoid arthritis (RA) is a chronic and autoimmune-mediated inflammatory disease. We aimed to investigate the regulation of lncRNA HOTAIR in LPS-treated chondrocytes and RA mouse. Our results showed that HOTAIR expression was significantly reduced in LPS-treated chondrocytes. The HOTAIR was then over-expressed in chondrocytes by transfecting recombinant lentivirus carrying sequences encoding HOTAIR. The LPS-induced reduction of cell proliferation rate and production of two inflammatory factors interleukin (IL)-17, IL-23 were markedly inhibited. Enforced expression of HOTAIR also led to the upregulation of proliferation-related protein Ki67 and proliferating cell nuclear antigen (PCNA). Moreover, a negative correlation was detected between the expression of HOTAIR and microRNA (miR)-138, and the expression of miR-138 was significantly increased in LPS-induced chondrocytes. The effects of HOTAIR over-expression on the proliferation and inflammation were partly reversed by miR-138 overexpression. Furthermore, the overexpression of HOTAIR significantly inhibited the activation of nuclear transcription factor-κB (NF-κB) in LPS-treated chondrocytes by suppressing p65 to cell nucleus, resulting in the down-regulation of IL-1β and tumor necrosis factor (TNF)-α. In addition, the in vivo experiments exhibited that overexpression of HOTAIR increased cell proliferation and inhibited inflammation in RA rats, which were demonstrated by upregulation of Ki67 and PCNA, reduced CD4+IL-17+,CD4+IL-23+ cells, and down-regulation of p-p65, IL-1β and TNF-α. In summary, our study suggests HOTAIR plays a protective role in RA by increasing proliferation rate and inhibiting inflammation, which may be related with the regulation of miR-138 expression and NF-κB signaling pathway. These results suggest that the regulation of HOTAIR may be a promising therapeutic strategy for RA.


A novel in vivo measure of cyberaggression.
Cyberaggression (CA), or the use of information communication technologies to inflict harm on others, is an emerging public health crisis. Unfortunately, our current ability to assess CA in a research context remains limited, curtailing efforts to address this important issue. We sought to fill this gap in the literature by developing an adapted "chat" version of the Taylor aggression paradigm (TAP) that would more closely resemble a social gaming format (hereafter referred to as the TAP-Chat). In the TAP-Chat, participants have a chat function available to communicate with their (fictitious) co-player. Following loss trials in a competitive reaction time task, they receive a "mean chat" from their co-player. Participant messages to their (fictitious) co-player are then coded for aggressive content by a team of trained research assistants, and via automated linguistic analysis software (Linguistic Inquiry and Word Count). The current study evaluated the predictive utility of the TAP-Chat task in independent discovery and replication samples (N = 843 and N = 350, respectively). Participants' publicly available tweets served as an important external criterion variable, along with a handful of self-report questionnaires assessing CA and related constructs. Analyses suggest that, although it can be completed in ∼13 min, the TAP-Chat predicts CA on Twitter and, to a lesser extent, as reported on questionnaires. Although there are still several issues to address, it is our hope that the research community will benefit from this straightforward behavioral assessment of CA.


Type IV pili-mediated secretion modulates Francisella virulence.
Francisella tularensis are the causative agent of the zoonotic disease, tularaemia. Among four F. tularensis subspecies, ssp. novicida (F. novicida) is pathogenic only for immunocompromised individuals, while all four subspecies are pathogenic for mice. This study utilized proteomic and bioinformatic approaches to identify seven F. novicida secreted proteins and the corresponding Type IV pilus (T4P) secretion system. The secreted proteins were predicted to encode two chitinases, a chitin binding protein, a protease (PepO), and a beta-glucosidase (BglX). The transcription of F. novicida pepO and bglX was regulated by the virulence regulator MglA. Intradermal infection of mice with F. novicida mutants defective in T4P secretion system or PepO resulted in enhanced F. novicida spread to systemic sites. Infection with F. novicida pepO mutants also resulted in increased neutrophil infiltration into the mouse airways. PepO is a zinc protease that is homologous to mammalian endothelin-converting enzyme ECE-1. Therefore, secretion of PepO likely results in increased production of endothelin and increased vasoconstriction at the infection site in skin that limits the F. novicida spread. Francisella human pathogenic strains contain a mutation in pepO predicted to abolish its secretion. Loss of PepO function may have contributed to evolution of highly virulent Francisellae.


Macrophage migration inhibitory factor is involved in the pathogenesis of collagen type II-induced arthritis in mice.
To determine the importance of macrophage migration inhibitory factor (MIF) in the development of arthritis we used an experimental model for rheumatoid arthritis, collagen type II (CII)-induced arthritis in mice. Treatment with neutralizing anti-MIF Abs before immunization of (B10.Q x DBA/1)F1 with CII led to delayed onset and lowered frequency of arthritis. This was associated with lower levels of IgG2a to CII in MIF-depleted mice. The proliferative response to CII was stronger in the anti-MIF-treated mice, whereas no significant effects were seen on Ag-induced IFN-gamma production in response to CII or on the total serum Ab levels in response to CII. These results provide the first experimental evidence of a role for MIF in the pathogenesis of autoimmune disease.


Phylogeography of ancient and modern brown bears from eastern Eurasia.
The brown bear (Ursus arctos) is an iconic carnivoran species of the Northern Hemisphere. Its population history has been studied extensively using mitochondrial markers, which demonstrated signatures of multiple waves of migration, arguably connected with glaciation periods. Among Eurasian brown bears, Siberian populations remain understudied. We have sequenced complete mitochondrial genomes of four ancient (~4.5-40 kya) bears from South Siberia and 19 modern bears from South Siberia and the Russian Far East. Reconstruction of phylogenetic relationships between haplotypes and evaluation of modern population structure have demonstrated that all the studied samples belong to the most widespread Eurasian clade 3. One of the ancient haplotypes takes a basal position relative to the whole of clade 3; the second is basal to the haplogroup 3a (the most common subclade), and two others belong to clades 3a1 and 3b. Modern Siberian bears retain at least some of this diversity; apart from the most common haplogroup 3a, we demonstrate the presence of clade 3b, which was previously found mainly in mainland Eurasia and Northern Japan. Our findings highlight the importance of South Siberia as a refugium for northern Eurasian brown bears and further corroborate the hypothesis of several waves of migration in the Pleistocene.


Influence of patella alta on knee extensor mechanics.
The purpose of this study was to compare the knee extensor mechanics in persons with and without patella alta. Thirteen subjects with patella alta and 14 subjects with normal patellar position participated in the study. Sagittal and axial MR images of the knee were acquired at 0 degrees , 20 degrees , 40 degrees , and 60 degrees of knee flexion. Measurements of actual moment arm, patellar ligament/quadriceps tendon force ratio, quadriceps effective moment arm, and joint reaction force/quadriceps force ratio were obtained. There were no differences between groups in terms of actual moment arm. However, subjects with patella alta had significantly larger patellar ligament/quadriceps tendon force ratios (1.04+/-0.02 vs. 0.92+/-0.02) and quadriceps effective moment arms (4.40+/-0.09 vs. 4.00+/-0.09 cm) when averaged across the range of knee flexion angles tested. There was no difference in the joint reaction force/quadriceps force ratio between groups. The observed differences in knee extensor mechanics suggest that individuals with patella alta have a more efficient knee extensor mechanism and would be expected to generate similar joint reaction forces per unit quadriceps force compared to subjects with normal patellar position. Therefore, persons with patella alta may experience less patellofemoral joint reaction force to overcome the same knee flexion moment in the range of 0 degrees -60 degrees of knee flexion.


Radiotoxicity of platinum-195m-labeled trans-platinum (II) in mammalian cells.
The chemotoxicity and radiotoxicity of trans-dichlorodiammineplatinum (II) labeled with 195mPt (trans-195mPt) are investigated to ascertain the potential of radioplatinum coordination complexes as antineoplastic agents. Platinum-195m, with a half-life of about 4 days, is a prolific emitter of low-energy Auger electrons because of the high probability of internal conversion in its isomeric transitions. The kinetics of cellular uptake and retention after incubation and the radiotoxicity of this Auger electron emitter in the form of trans-195mPt is investigated using cells of the Chinese hamster V79 cell line. The cellular uptake of 195mPt reaches a plateau in about 3 to 5 h of incubation and varies nonlinearly with the extracellular concentration of radioactivity. The radioactivity is eliminated from the cells after incubation with an effective half-life of 24 h. Cell survival data, when corrected for the chemical toxicity of nonradiolabeled trans-platinum, give a cell survival curve typical for radiations with high linear energy transfer. At 37% survival, the mean lethal cellular uptake is about 1.0 mBq/cell. Dosimetric considerations, based on subcellular distribution of the radionuclide, yield a value of 4.8 for the relative biological effectiveness when compared with 250 kVp X rays. Theoretical Monte Carlo track-structure calculations indicate that the density of radical species produced in liquid water in the immediate vicinity of a 195mPt decay site is substantially greater than the density of species along the track of a 5.3 MeV alpha particle. This explains qualitatively the efficacy of 195mPt in causing high-LET radiation type biological effects. The extreme radiotoxicity of intranuclearly localized 195mPt, in conjunction with the proclivity of platinum chemotherapy agents to bind to DNA in the cell nucleus, suggests that the combination of chemical effects and the effects of Auger electrons that can be obtained with radioplatinum coordination complexes may have potential in the treatment of cancer.


Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation.
Immature Schwann cells found in perinatal rodent nerves are generated from Schwann cell precursors (SCPs) that originate from the neural crest. Immature Schwann cells generate the myelinating and non-myelinating Schwann cells of adult nerves. When axons degenerate following injury, Schwann cells demyelinate, proliferate and dedifferentiate to assume a molecular phenotype similar to that of immature cells, a process essential for successful nerve regeneration. Increasing evidence indicates that Schwann cell dedifferentiation involves activation of specific receptors, intracellular signalling pathways and transcription factors in a manner analogous to myelination. We have investigated the roles of Notch and the transcription factor c-Jun in development and after nerve transection. In vivo, Notch signalling regulates the transition from SCP to Schwann cell, times Schwann cell generation, controls Schwann cell proliferation and acts as a brake on myelination. Notch is elevated in injured nerves where it accelerates the rate of dedifferentiation. Likewise, the transcription factor c-Jun is required for Schwann cell proliferation and death and is down-regulated by Krox-20 on myelination. Forced expression of c-Jun in Schwann cells prevents myelination, and in injured nerves, c-Jun is required for appropriate dedifferentiation, the re-emergence of the immature Schwann cell state and nerve regeneration. Thus, both Notch and c-Jun are negative regulators of myelination. The growing realisation that myelination is subject to negative as well as positive controls and progress in molecular identification of negative regulators is likely to impact on our understanding of demyelinating disease and mechanisms that control nerve repair.


Early-onset encephalopathy and cortical myoclonus in a boy with MECP2 gene mutation.
The authors report the unusual clinical and neurophysiologic features of a sporadic case of a boy carrying an 806delG mutation on the MECP2 gene. A 28-month-old boy was examined for severe developmental delay, seizures, microcephaly, breathing dysfunction, and spontaneous and evoked myoclonic jerks of upper limbs. Neurophysiologic study proved the cortical origin of myoclonus; however, it was not associated with signs of cortical hyperexcitability. 3-Methoxy-4-hydroxy-phenylethylene glycol and valine concentrations were low in CSF.


The variable, C(H)1, C(H)2 and C(H)3 domains of Ig heavy chain are dispensable for pre-BCR function in transgenic mice.
The pre-BCR consists of Ig micro protein, the product of a heavy chain gene assembled by V(D)J recombination in pro-B cells, the surrogate light chains V(pre-B) and lambda 5, and the signaling chains Ig alpha and Ig beta. Signaling by the pre-BCR is a checkpoint required for further maturation of pro-B cells in the adult bone marrow. However, it is currently not known whether an extracellular ligand is required to initiate pre-BCR signaling. We reasoned that if the ectodomain of the pre-BCR is required to interact with a ligand, then a truncated heavy chain protein would not support B cell development. To test this notion, we produced transgenic mice expressing a heavy chain protein whose extracellular domains except for C(H)4 were replaced by an irrelevant Ig superfamily ectodomain from the human CD8 alpha protein. This transgene resulted in pre-BCR-like signaling since it rescued development of pre-B cells in recombinase-activating gene (RAG)1-deficient mice and resulted in allelic exclusion of the endogenous Ig heavy chain gene in RAG-proficient mice. These findings lead us to suggest that the majority of the extracellular region of the pre-BCR is not required for pre-BCR function and, thus, ligand binding is unlikely to be required for pre-BCR function.


A bacterial gene, mms6, as a new reporter gene for magnetic resonance imaging of mammalian cells.
Magnetic resonance imaging (MRI) allows for noninvasive, deep tissue imaging with high spatial resolution, making it an attractive modality for in vivo cellular imaging. Since reporter genes can generate magnetic resonance (MR) contrast based on molecular activity, they offer a potentially powerful tool for cellular imaging. The mms6 gene was originally identified in magnetotactic bacteria (MTB), which is known to play a key role in magnetic crystal formation. The purpose of the present work was to investigate the possibility of using mms6 as an MR reporter gene. We established a transgenic mammalian cell line that stably expresses mms6. In vitro experiments show that mms6-expressing cells form clusters of nanoparticles within and outside membrane-enclosed structures and produce changes in MR contrast, most likely by increasing iron uptake of intracellular iron. Additionally, in vivo MRI experiments demonstrate that mms6-expressing tumors can be distinguished from parental tumors not expressing mms6, even in the absence of exogenous iron supplementation. Our results demonstrate that mms6 can function as an MR reporter gene with the potential to monitor gene expression and to visualize the proliferation, migration, and metastasis of tumor cells expressing it.


The escape problem for mortal walkers.
We introduce and investigate the escape problem for random walkers that may eventually die, decay, bleach, or lose activity during their diffusion towards an escape or reactive region on the boundary of a confining domain. In the case of a first-order kinetics (i.e., exponentially distributed lifetimes), we study the effect of the associated death rate onto the survival probability, the exit probability, and the mean first passage time. We derive the upper and lower bounds and some approximations for these quantities. We reveal three asymptotic regimes of small, intermediate, and large death rates. General estimates and asymptotics are compared to several explicit solutions for simple domains and to numerical simulations. These results allow one to account for stochastic photobleaching of fluorescent tracers in bio-imaging, degradation of mRNA molecules in genetic translation mechanisms, or high mortality rates of spermatozoa in the fertilization process. Our findings provide a mathematical ground for optimizing storage containers and materials to reduce the risk of leakage of dangerous chemicals or nuclear wastes.


Chloroplast-derived anthrax and other vaccine antigens: their immunogenic and immunoprotective properties.
Transgenic plants offer many advantages, including low cost of production (by elimination of fermenters), storage and transportation, heat stability, absence of human pathogens, protection of antigens in the stomach through bioencapsulation (when delivered orally), elimination of the need for expensive purification and sterile injections and generation of both systemic and mucosal immunity. Recent studies have demonstrated that chloroplast-derived anthrax-protective antigen elicits effective immune responses, develops neutralizing antibodies, confers complete protection against anthrax lethal toxin challenge and produces 360 million doses of vaccine in one acre of transgenic plants. Chloroplast-derived vaccine antigens are efficacious against bacterial, fungal, viral and protozoan pathogens.


Electroactive supramolecular self-assembled fibers comprised of doped tetrathiafulvalene-based gelators.
New electroactive supramolecular fibers have been formed by self-assembly of the derivatives of tetrathiafulvalene (TTF) in liquid crystals. These derivatives are designed and prepared by introducing the TTF moiety to the scaffold derived from amino acids such as L-isoleucine whose derivatives function as organogelators. These TTF-based gelators form stable fibrous aggregates in liquid crystals. These fibers are the first example of hydrogen-bonded one-dimensional aggregates having electroactive moieties whose electrical conductivities were measured after doping. Their electronic states have also been characterized by spectroscopic methods. Unidirectionally aligned fibers are formed in the oriented liquid crystal solvents on the rubbed polyimide surface for further functionalization of the fibers.


Multi-location trials and population-based genotyping reveal high diversity and adaptation to breeding environments in a large collection of red clover.
Red clover (Trifolium pratense L.) is an outcrossing forage legume that has adapted to a wide range of climatic and growing conditions across Europe. Red clover is valued for its high yield potential and its forage quality. The high amount of genetic diversity present in red clover provides an invaluable, but often poorly characterized resource to improve key traits such as yield, quality, and resistance to biotic and abiotic stresses. In this study, we examined the genetic and phenotypic diversity within a diverse set of 395 diploid red clover accessions via genome wide allele frequency fingerprinting and multi-location field trials across Europe. We found that the genetic structure of accessions mostly reflected their geographic origin and only few cases were detected, where breeders integrated foreign genetic resources into their local breeding pools. The mean dry matter yield of the first main harvesting season ranged from 0.74 kg m-2 in Serbia and Norway to 1.34 kg m-2 in Switzerland. Phenotypic performance of accessions in the multi-location field trials revealed a very strong accession x location interaction. Local adaptation was especially prominent in Nordic red clover accessions that showed a distinct adaptation to the growing conditions and cutting regime of the North. The traits vigor, dry matter yield and plant density were negatively correlated between the trial location in Norway and the locations Great Britain, Switzerland, Czech Republic and Serbia. Notably, breeding material and cultivars generally performed well at the location where they were developed. Our results confirmed that red clover cultivars were bred from regional ecotypes and show a narrow adaptation to regional conditions. Our study can serve as a valuable basis for identifying interesting materials that express the desired characteristics and contribute to the adaptation of red clover to future climatic conditions.


Thermal Processing of a Degradable Carboxylic Acid-Functionalized Polycarbonate into Scaffolds for Tissue Engineering.
Degradable polymers are often desirable for the fabrication of medical implants, but thermal processing of these polymers is a challenge. We describe here how these problems can be addressed by discussing the extrusion of fibers and injection molding of bone pins from a hydrolytically degradable tyrosine-derived polycarbonate. Our initial attempts produced fibers and pins with bubbles, voids, and discoloration, and resulted in the formation of large polymer plugs that seized screws and blocked extruder dies. The material and process parameters that contribute to these issues were investigated by studying the physical and chemical changes that occur during processing. Differential scanning calorimetry (DSC) scans and thermogravimetric analysis combined with IR (TGA-IR) analysis revealed the role of residual moisture and residual solvents that in conjunction with heat cause degradation and crosslinking as indicated by gel permeation chromatography (GPC). Rheology and melt-flow index measurements were useful in characterizing the extent of dependence of polymer viscosity on temperature and molecular weight. With these insights, we could process our polymer into fibers and rods by controlling residual moisture, time and temperature, and by adjusting processing parameters in real-time. The systematic approach described here is applicable to other degradable polymers that are difficult to process.


A Novel Method to Locate Intracranial Anatomic Landmarks of Sella Using Three-Dimensional Computed Tomography Reconstruction Images for Endoscopic Endonasal Transsphenoidal Surgery.
To help surgeons to locate the intracranial anatomic landmarks when performing endoscopic endonasal tanssphenoidal surgery using measurements based on three-dimensional computed tomography (CT) reconstruction images. High-resolution axial CT images at the thickness of 0.6 mm, and reconstructed 0.41-mm-thick gapless sagittal and coronal CT images were taken from 111 subjects. Using mimics software, first located the points of nasal spine, midpoint of the posterior hard palate and the basic line between them. Then located the medial edge of foramen lacerums, optic canals, midpoints of tuberculum sellae and posterior-inferior sellar floor, measured their distances to nasal spine and angles between the line connecting these structures to nasal spine and the basic line. The mean distance from nasal spine to optic canal is 73.12 ± 4.10 mm, and the corresponding angle is 39.79° ± 3.13°. The distance from the medial edge of foramen lacerum to nasal spine is 79.91 ± 4.01 mm, and the corresponding angle is 23.27° ± 2.89°. The distances from midpoints of the tuberculum sellae and posterior-inferior sellar floor to nasal spine are 76.16 ± 4.56 mm and 82.05 ± 4.81 mm, and the corresponding angles are 34.97° ± 3.24° and 26.39° ± 3.51°, respectively. The distances between both foramen lacerums and optic canals are 22.54 ± 3.25 and 23.44 ± 3.49 mm, respectively. The distance from the midpoint of tuberculum sellae to posterior-inferior sellar floor is 13.33 ± 1.87 mm. The current study provides information about intracranial anatomic landmarks, which can help neurosurgeons to locate them and avoid relative complications during endoscopic endonasal transsphenoid surgery. The measurements can be used as surgical indicators to investigate these anatomic landmarks.


Synthesis, electrochemistry and luminescence of [Pt{4'-(R)trpy}(CN)](+) (R = Ph, o-CH(3)C(6)H(4), o-ClC(6)H(4) or o-CF(3)C(6)H(4); trpy = 2,2':6',2''-terpyridine): crystal structure of [Pt{4'-(Ph)trpy}(CN)]BF(4) x CH(3)CN.
The synthesis and characterization of [Pt{4'-(R)trpy}(CN)]X (R = Ph, X = BF(4) or SbF(6); R = o-CH(3)C(6)H(4), X = SbF(6); R = o-ClC(6)H(4), X = SbF(6); or R = o-CF(3)C(6)H(4), X = SbF(6)) are described where trpy = 2,2':6',2''-terpyridine. Single crystals of [Pt{4'-(Ph)trpy}(CN)]BF(4).CH(3)CN were grown by vapour diffusion of diethyl ether into an acetonitrile solution of [Pt{4'-(Ph)trpy}(CN)]BF(4). An X-ray crystal structure determination of the solvated complex confirms the near linear coordination of the cyanide ligand to the platinum centre. The cation is almost planar as evidenced by a twist of only 1.9 degrees of the phenyl group out of the plane of the terpyridyl moiety. Cyclic voltammograms were recorded in DMF/0.1 M TBAH for the [Pt{4'-(R)trpy}(CN)](+) cations. Two quasi-reversible one-electron reduction (cathodic) waves are observed with E(1/2) values that show the trend expected for an increasingly lower energy of the trpy-based LUMO of the complex i.e., [Pt{4'-(Ph)trpy}(CN)](+) approximately [Pt{4'-(o-CH(3)C(6)H(4))trpy}(CN)](+) < [Pt{4'-(o-ClC(6)H(4))trpy}(CN)](+) < [Pt{4'-(o-CF(3)C(6)H(4))trpy}(CN)](+). All the [Pt(4'-(R)trpy}(CN)](+) cations are photoluminescent in dichloromethane. Emission by [Pt{4'-(Ph)trpy}(CN)](+) is from an excited state with largely (3)MLCT orbital parentage, but with some intraligand (3)pi-pi* character mixed-in (tau = 0.1 micros). In contrast, the other three cations display emission that appears exclusively intraligand (3)pi-pi* in origin (tau approximately 0.8 micros). Emission spectra have been recorded in a low concentration frozen DME {1 : 5 : 5 (v/v) DMF-MeOH-EtOH} glass. For the R = o-CH(3)C(6)H(4), o-ClC(6)H(4) and o-CF(3)C(6)H(4) cations the envelope of vibronic structure and energies of the vibrational components are essentially the same as that recorded in dichloromethane. However, for the [Pt{4'-(Ph)trpy}(CN)](+) cation, there is a blue-shift in the energies of the vibrational components as compared to that recorded in dichloromethane, as well as a change in the envelope of vibronic structure to a more "domed" pattern; this has been interpreted in terms of a higher percentage of intraligand (3)pi-pi* character in the emitting state for the glass. Increasing the concentration of the glass invariably leads to aggregation of the cations and the consequent development of new low energy bands, such that at 0.200 mM broad peaks centred at ca. 650 and 700 nm dominate the spectrum; these bands are assigned to excimeric (3)pi-pi* and (3)MMLCT emission, respectively.


Modular Organization of Exploratory Force Development Under Isometric Conditions in the Human Arm.
Muscle coordination of isometric force production can be explained by a smaller number of modules. Variability in force output, however, is higher during exploratory/transient force development phases than force maintenance phase, and it is not clear whether the same modular structure underlies both phases. In this study, eight neurologically-intact adults isometrically performed target force matches in 54 directions at hands, and electromyographic (EMG) data from eight muscles were parsed into four sequential phases. Despite the varying degree of motor complexity across phases (significant between-phase differences in EMG-force correlation, angular errors, and between-force correlations), the number/composition of motor modules were found equivalent across phases, suggesting that the CNS systematically modulated activation of the same set of motor modules throughout sequential force development.


KNN-Based Lead-Free Piezoelectric Ceramics with High Qm and Enhanced d33 via a Donor-Acceptor Codoping Strategy.
The wide application of KNN-based lead-free piezoelectric ceramics is constrained by the contradictory relationship between its mechanical quality factor and piezoelectric constant. From an application point of view, searching for chemical composition with enhanced piezoelectric constant (d33) and mechanical quality factor (Qm) is one of the key points of KNN-based ceramics. In this work, KNN-based ceramics with enhanced d33 and high Qm values were obtained by the solid solution method via a donor-acceptor codoping strategy. The donor dopant Ho3+ enhanced d33 values by refining the domain size, while the acceptor dopant (Cu1/3Nb2/3)4+ improved Qm by the formation of defect dipoles. The composition (KNN-5Ho-4CN) exhibits optimal integrated performances, of which d33, Qm, and TC values are 120 pC/N, 850, and 392 °C, respectively. Moreover, the temperature coefficient of resonant frequency (TCF = -429 ppm/K) indicates that KNN-5Ho-4CN ceramic has good temperature stability. This work provides a new insight for developing KNN-based ceramics with enhanced d33 and high Qm.


[Thoracic outlet syndrome with arterial complication treated by the subclavicular transsternal approach: report of a case].
A 42-year-old female was referred to our vascular service because of her right arm fatigue and cold sensitivity. On elevation of right arm, her radial pulse was absent with pallor of the hand. Angiography demonstrated a significant stenosis of the right subclavian artery, which was considered to be complication of thoracic outlet syndrome. We performed resection of the first rib using the standard subclavicular approach and the subclavian-subclavian artery bypass using a new transsternal extension approach to the subclavian artery. After follow-up 18 months, she was working and asymptomatic. This transsternal extension is effective to treat the arterial complication after decompression of the thoracic outlet.


Inelastic compression increases venous ejection fraction more than elastic bandages in patients with superficial venous reflux.
To investigate the influence of compression bandages, manufactured using materials with different elastic properties, on the impaired venous pumping function in patients with venous insufficiency. Ejection volume (EV) and ejection fraction (EF) were measured using strain gauge plethysmography distal from the patella without and with elastic and inelastic compression bandages in a total of 30 patients with major venous reflux in the great saphenous vein. The interface pressure of the bandages was measured simultaneously in the medial gaiter area. Normal values of EV and EF were obtained from 15 healthy controls. Patients with venous insufficiency showed a statistically significant reduction of EV and EF compared to controls. Elastic bandages with an average pressure of 42 mm Hg in the supine position achieved a moderate increase of EV and a significant improvement of EF (p < .01), while inelastic bandages applied with comparable resting pressure (41 mm Hg) raised EV and EF into a normal range (p < .001). The improvement of the ejection fraction correlates well with the pressure differences between standing and lying (Static Stiffness Index) and between muscle systole and diastole during exercise (Pearson r = 0.69 and 0.74 respectively, p < .001). Elastic bandages applied with high stretch in order to achieve standing pressures comparable to those of inelastic bandages (>60 mm Hg) led only to a minor improvement of the venous pumping function. Ejected volume and ejection fraction, which are severely reduced in venous insufficiency, can be increased by compression therapy. Inelastic compression is much more effective than elastic bandages, and is able to normalize venous pumping function. With elastic bandages EV and EF always remain below the normal range even when applied with high stretch producing a resting pressure that is barely tolerable.


Unexpected Ring Expansion of a Four-Membered Cyclophosphazane.
Nucleophilic substitution reactions of the N(R),N(R)-spiro-bridged octachlorobis(cyclotriphosphazene), N3P3Cl4[N(CH2)5CH3]2N3P3Cl4 (1), with sodium salts of alcohols (1,3-propanediol, 2,2,3,3,4,4-hexafluoro-1,5-pentanediol, and phenol) give ansa products (2-4) via an unexpected rearrangement. These products were characterized by elemental analysis, mass spectrometry, and (1)H and (31)P NMR spectroscopy. The molecular structures of compounds 3 and 4 were also established by X-ray crystallography. This new class of phosphazene structures consists of three fused P3N3 rings that arise from expansion of the four-membered phosphazane ring in 1 to a six-membered N3P3 ring during alcoholysis reactions.


Recql5 protects against lipopolysaccharide/D-galactosamine-induced liver injury in mice.
To investigate the effects of Recql5 deficiency on liver injury induced by lipopolysaccharide/D-galactosamine (LPS/D-Gal). Liver injury was induced in wild type (WT) or Recql5-deficient mice using LPS/D-Gal, and assessed by histological, serum transaminases, and mortality analyses. Hepatocellular apoptosis was quantified by transferase dUTP nick end labeling assay and Western blot analysis of cleaved caspase-3. Liver inflammatory chemokine and cytochrome P450 expression was analyzed by quantitative reverse transcription-PCR. Neutrophil infiltration was evaluated by myeloperoxidase activity. Expression and phosphorylation of ERK, JNK, p65, and H2A.X was determined by Western blot. Oxidative stress was evaluated by measuring malondialdehyde production and nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity. Following LPS/D-Gal exposure, Recql5-deficient mice exhibited enhanced liver injury, as evidenced by more severe hepatic hemorrhage, higher serum aspartate transaminase and alanine transaminase levels, and lower survival rate. As compared to WT mice, Recql5-deficient mice showed an increased number of apoptotic hepatocytes and higher cleaved caspase-3 levels. Recql5-deficient mice exhibited increased DNA damage, as evidenced by increased γ-H2A.X levels. Inflammatory cytokine levels, neutrophil infiltration, and ERK phosphorylation were also significantly increased in the knockout mice. Additionally, Recql5-deficient mice exhibited increased malondialdehyde production and elevated inducible nitric oxide synthase, superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase activity, indicative of enhanced oxidative stress. Moreover, CYP450 expression was significantly downregulated in Recql5-deficient mice after LPS/D-Gal treatment. Recql5 protects the liver against LPS/D-Gal-induced injury through suppression of hepatocyte apoptosis and oxidative stress and modulation of CYP450 expression.


The effect of seed bacterization with Bacillus paralicheniformis 2R5 on bacterial and fungal communities in the canola rhizosphere.
Bacillus sp. is one of the best-studied plant growth-promoting rhizobacteria (PGPR). However, more detailed studies targeting its effect on the rhizosphere microbial community are required for improving management practices regarding its commercial application in the field. Our earlier study showed that PGPR Bacillus paralicheniformis 2R5 stimulated canola growth. Hence, this study aimed to assess the time-course impact of B. paralicheniformis 2R5 on bacterial and fungal community structure and diversity. The results showed that inoculation with B. paralicheniformis 2R5 initially significantly decreased the observed bacterial richness compared to the control, while after 44 days of treatment this alpha diversity metrics increased. A linear discriminant analysis effect size showed that B. paralicheniformis 2R5 altered the soil bacterial and fungal community structure by increasing the abundance of plants' beneficial microorganisms such as Nitrospira, Ramlibacter, Sphingomonas, Massilia, Terrimonas as well as Solicoccozyma, Schizothecium, Cyphellophora, Fusicolla, Humicola. B. paralicheniformis 2R5 seems to be a promising alternative to chemical pesticides and can be considered for practical application in the field. Its ability to alter the rhizosphere microbiome by increasing the diversity and composition of bacterial communities and increasing plants' beneficial groups of fungi, appears to be important in terms of improving canola development. However, further studies on these increased microbial taxa are necessary to confirm their function in promoting canola growth.


National Estimates of Noncanine Bite and Sting Injuries Treated in US Hospital Emergency Departments, 2011-2015.
Injuries resulting from contact with animals are a significant public health concern. This study quantifies and updates nonfatal bite and sting injuries by noncanine sources using the most recent data available (2011-2015) from the National Electronic Injury Surveillance System-All Injury Program with the purpose of using these updates to better understand public health consequences and prevention techniques. Increased rates of bites and stings can be expected in this study's time frame, possibly caused by the increasing human population expanding into animal territories, as well as changes in animal geographic distribution and pet ownership. The National Electronic Injury Surveillance System-All Injury Program is an ongoing nationally representative surveillance system used to monitor all types and causes of injuries treated in US hospital emergency departments (EDs). Cases were coded by trained hospital coders using information from medical records on animal sources of bite and sting injuries being treated. Data from 2011-2015 were weighted to produce national annualized estimates, percentages, and rates based on the US population. An estimated 1.17 million people visited EDs for noncanine bite and sting injuries annually. This translates to a rate of 371.3/100,000 people. Insects accounted for 71.0% of noncanine bite and sting injuries, followed by arachnids (19.2%) and mammals (7.8%). The estimated annual total lifetime medical and work cost of unintentional noncanine injuries was $5,755,581,000. Various sources of bite and sting injuries had an outsized effect on injury rates and identify potential areas of focus for education and prevention programs to reduce the burden of these injuries on health and healthcare costs. The study describes the diversity of animal exposures based on a national sample of EDs. Noncanine bite and sting injuries significantly affect public health and healthcare resources. Priorities can be focused on animal sources with the most impact on bite and sting injury rates, healthcare costs, and disease burden.


Isolation and identification of active ingredients and biological activity of Dioscorea nipponica Makino.
This study reported the isolation and identification of bioactive compounds from Dioscorea nipponica Makino, a plant used in traditional medicine for various ailments. Nine compounds were isolated, including a new compound named as diosniposide E, which was elucidated by analyzing its 1H-NMR, 13C-NMR, DEPT, COSY, HMBC and MS data and comparing them with data available in literature. The other eight compounds were identified as known compounds. Theoretical calculations of energy and the generation of a molecular electrostatic potential surface map were employed to assess the antioxidant capacity of nine compounds, the calculation results exhibited that compounds 5 and 6 had strong antioxidant capacities. To further evaluate the antioxidant activities of the investigated compounds, the DPPH and ABTS assays were conducted. The results from the DPPH scavenging activity test revealed that compounds 4-6 exhibited enhanced scavenging activities compared to L-ascorbic acid, while displaying similar efficacy to trolox. Moreover, the ABTS scavenging activities of compounds 4-6 were found to surpass those of L-ascorbic acid and trolox. In terms of α-glucosidase inhibition, compounds 3 and 4 displayed remarkable inhibitory activities that surpassed the effects of acarbose. Additionally, compound 2 exhibited potent anticholinesterase activities, outperforming donepezil. This research provides insights into the potential bioactive compounds present in Dioscorea nipponica Makino and may contribute to its use in traditional medicine.


[Amnestic episodes in migraine. A contribution to the differential diagnosis of transient global amnesia (ictus amnésique)].
In comparison with 27 similar cases, sampled from literature, 4 observations of amnesic episodes in migraine are presented and discussed. These disturbances known as so-called "Migranedammerattacken" seem to be identical with transient global amnesia in all respects. In most of cases, they occur as migraine-precursors or - equivalents. Headache, vegetative und neurological symptoms are frequent but not necessary companions. It is proposed to look for migraine disposition in all cases of transient global amnesia. Perhaps, this approach might be of some use to understand their enigmatic pathogenesis.


An ion-exchange mechanism of cartilage calcification.
The provisional calcification of epiphyseal cartilage involves deposition of hydroxyapatite (calcium phosphate) crystals in an extracellular matrix consisting principally of Type II collagen and cartilage proteoglycan. A mechanism is now proposed to explain how epiphyseal cartilage calcification is initiated. Calcium exists at high concentration in cartilage, but is mainly bound to the anionic groups of proteoglycans, and thus is unavailable for precipitation. A local increase in phosphate concentration displaces calcium ions from proteoglycan by an ion-exchange effect, raising the Ca X PO4 product above the threshold for precipitation of hydroxyapatite. Evidence for this hypothesis has been derived from studies of the effect of phosphate on the binding of calcium to cartilage proteoglycan, and on hydroxyapatite formation in the presence of chondroitin sulfate.


Arsenic exposure in pregnancy increases the risk of lower respiratory tract infection and diarrhea during infancy in Bangladesh.
Previous studies have reported associations between prenatal arsenic exposure and increased risk of infant mortality. An increase in infectious diseases has been proposed as the underlying cause of these associations, but there is no epidemiologic research to support the hypothesis. We evaluated the association between arsenic exposure in pregnancy and morbidity during infancy. This prospective population-based cohort study included 1,552 live-born infants of women enrolled during 2002-2004 in Matlab, Bangladesh. Arsenic exposure was assessed by the concentrations of metabolites of inorganic arsenic in maternal urine samples collected at gestational weeks 8 and 30. Information on symptoms of lower respiratory tract infection (LRTI) and diarrhea in infants was collected by 7-day recalls at monthly home visits. In total, 115,850 person-days of observation were contributed by the infants during a 12-month follow-up period. The estimated risk of LRTI and severe LRTI increased by 69% [adjusted relative risk (RR) = 1.69; 95% confidence interval (CI), 1.36-2.09)] and 54% (RR = 1.54; 95% CI, 1.21-1.97), respectively, for infants of mothers with urinary arsenic concentrations in the highest quintile (average of arsenic concentrations measured in early and late gestation, 262-977 µg/L) relative to those with exposure in the lowest quintile (< 39 µg/L). The corresponding figure for diarrhea was 20% (RR = 1.20; 95% CI, 1.01-1.43). Arsenic exposure during pregnancy was associated with increased morbidity in infectious diseases during infancy. Taken together with the previous evidence of adverse effects on health, the findings strongly emphasize the need to reduce arsenic exposure via drinking water.


Omics-driven investigation of the biology underlying intrinsic submaximal working capacity and its trainability.
Submaximal exercise capacity is an indicator of cardiorespiratory fitness with clinical and public health implications. Submaximal exercise capacity and its response to exercise programs are characterized by heritability levels of about 40%. Using physical working capacity (power output) at a heart rate of 150 beats/min (PWC150) as an indicator of submaximal exercise capacity in subjects of the HERITAGE Family Study, we have undertaken multi-omics and in silico explorations of the underlying biology of PWC150 and its response to 20 wk of endurance training. Our goal was to illuminate the biological processes and identify panels of genes associated with human variability in intrinsic PWC150 (iPWC150) and its trainability (dPWC150). Our bioinformatics approach was based on a combination of genome-wide association, skeletal muscle gene expression, and plasma proteomics and metabolomics experiments. Genes, proteins, and metabolites showing significant associations with iPWC150 or dPWC150 were further queried for the enrichment of biological pathways. We compared genotype-phenotype associations of emerging candidate genes with reported functional consequences of gene knockouts in mouse models. We investigated the associations between DNA variants and multiple muscle and cardiovascular phenotypes measured in HERITAGE subjects. Two panels of prioritized genes of biological relevance to iPWC150 (13 genes) and dPWC150 (6 genes) were identified, supporting the hypothesis that genes and pathways associated with iPWC150 are different from those underlying dPWC150. Finally, the functions of these genes and pathways suggested that human variation in submaximal exercise capacity is mainly driven by skeletal muscle morphology and metabolism and red blood cell oxygen-carrying capacity.NEW & NOTEWORTHY Multi-omics and in silico explorations of the genes and underlying biology of submaximal exercise capacity and its response to 20 wk of endurance training were undertaken. Prioritized genes were identified: 13 genes for variation in submaximal exercise capacity in the sedentary state and 5 genes for the response level to endurance training, with no overlap between them. Genes and pathways associated with submaximal exercise capacity in the sedentary state are different from those underlying trainability.


Effective Screening and Classification of Cervical Precancer Biopsy Imagery.
Microscope images of biopsy samples of cervical precancers conventionally discriminated by histopathology, the current "gold standard" for cancer detection, showed that their correlation properties are segregated into different classes. The correlation domains clearly indicate increasing cellular clustering in different grades of precancer compared with their normal counterparts. This trend indicates the probability of pixel distribution of the corresponding tissue images. Because the cell density is not uniform in the higher grades, the skewness (asymmetry of a distribution), kurtosis (sharpness of a distribution), entropy (randomness), and standard deviation are affected. A combination of these parameters effectively improves the diagnosis and quantitatively classifies the normal and all the three grades of precancerous cervical tissue sections significantly. Thus, the statistical analysis of microscope images is a promising approach for early stage tumor detection and quantitative classification of precancerous grades; this can effectively supplement the qualitative analysis by the pathologist.


One step synthesis of highly photoluminescent red light-emitting carbon dots from O-phenylenediamine and 2,4-diaminophenol as fluorescent probes for the detection of pH and Cr(VI).
In this study, new red light-emitting carbon dots (R-CDs) that can selectively recognize Cr(VI) were prepared using a strategy that utilizes 2,4-diaminophenol to enhance the fluorescence of O-phenylenediamine based carbon dots. The results showed that 2,4-diaminophenol increased the quantum yield (QY) of the carbon quantum dots (CDs), and that the QY of the CDs increased from their original value of 8.7% to 20.1% (R-CDs). The R-CDs show sensitivity to acidic conditions and maintain good linearity between pH = 1.00-4.00, making them useful as pH probes. Furthermore, the prepared R-CDs possess good solubility in water and are responsive to changes in Cr(VI) concentrations in aqueous environments. The quenching of the R-CDs fluorescence was linearly correlated with the Cr(VI) concentration within a range of 0-20 μM, with a lower detection limit of 66 nM. The detection mechanism is attributed to the formation of hydrogen bonds between Cr(VI) and the R-CDs, resulting in the fluorescence quenching of the R-CDs. The R-CDs can be considered effective multifunctional fluorescent probes for both pH and Cr(VI) in aqueous environments. This study will provide new R-CD design strategies for probes that selectively identify specific target substances.


Left molar approach improves laryngeal view in patients with simulated limitation of cervical movements.
Immobilized cervical spine, because of either diseases or stabilizing devices, poses considerable difficulties with endotracheal intubation due to poor laryngoscopic view. The left molar (LM) approach has been shown to be useful in difficult sporadic intubation cases. We evaluated efficacy of this approach of laryngoscopy to improve laryngeal view in patients with simulated limitation of cervical movements. Thirty patients of American Society of Anesthesiologists grade I/II, who were scheduled to undergo routine surgical procedures under general anaesthesia and endotracheal intubation, were studied. A two-piece semi-rigid cervical collar was used to immobilize the cervical spine. Under standardized anaesthesia and neuromuscular blocking agent, conventional laryngoscopy using a curved Macintosh blade was performed and glottic view was recorded with and without optimal external laryngeal manipulation (OELM). Subsequently, in the same subjects the laryngoscope blade was withdrawn and re-inserted through the LM approach and glottic view was recorded with and without OELM followed by tracheal intubation. With the conventional approach, laryngeal view was recorded as grade II in five patients, grade III in 24 patients, and grade IV in one patient. However, with the LM approach, laryngeal view was grade I in 25 patients, grade II in five patients, and grade III or IV in none (P<0.001). Tracheal intubation with the LM approach required the use of a flexible stylet to guide the tube tip into the larynx. The laryngeal view is improved by the LM approach in patients with simulated limited cervical movements with a high success rate of tracheal intubation, but requires orientation for negotiation of the tube through the narrow oropharyngeal space available.


Induction of natural competence in Streptococcus pneumoniae triggers lysis and DNA release from a subfraction of the cell population.
Naturally competent bacteria have the ability to take up free DNA from the surrounding medium and incorporate this DNA into their genomes by homologous recombination. In naturally competent Streptococcus pneumoniae, and related streptococcal species from the mitis phylogenetic group, the competent state is not a constitutive property but is induced by a peptide pheromone through a quorum-sensing mechanism. Recent studies have shown that natural genetic transformation is an important mechanism for gene exchange between streptococci in nature. A prerequisite for effective gene exchange is the presence of streptococcal donor DNA in the environment. Despite decades of study of the transformation process we still do not know how this donor DNA is released from streptococcal cells to the external milieu. Traditionally, it has been assumed that donor DNA originates from cells that die and fall apart from natural causes. In this study we show that induction of the competent state initiates release of DNA from a subfraction of the bacterial population, probably by cell lysis. The majority of the cells induced to competence take up DNA and act as recipients, whereas the rest release DNA and act as donors. These findings show that natural transformation in streptococci provides a natural mechanism for genetic recombination that resembles sex in higher organisms.


The efficacy of probiotics on the prevention of pouchitis for patients after ileal pouch-anal anastomosis: A meta-analysis.
To date, a few studies indicated that probiotics are beneficial to pouchitis, but no meta-analyses summarized the outcomes of probiotics in pouchitis in detail. This meta-analysis discusses probiotics in the prevention of pouchitis for patients after ileal pouch-anal anastomosis (IPAA) and the relationship between probiotics preventive effect and the duration of therapy and history. PubMed, EMBASE and Cochrane Library databases were searched from inception until February 2022. Risk ratio (RR), mean difference (MD) and their 95% confidence interval (CI) were analyzed by Review Manager 5.3. The subgroup analysis was also performed to explore the agent for influencing outcomes. A total of 8 studies were included in this meta-analysis. The incidence of pouchitis in probiotics was significantly lower than that in the control (RR = 0.19, 95%CI [0.12, 0.32], Pï¼ 0.00001), and the PDAI (pouchitis disease activity index) in probiotics was also significantly lower (MD =-5.65, 95%CI [-9.48, -1.83]). After the subgroup analysis, we found that probiotics work better in the short-term (RR = 0.12, 95%CI [0.04, 0.40], P= 0.0004), but may not achieve the desired effect in the long-term (RR = 1.20, 95%CI [0.40, 3.60], P= 0.75). Probiotics are beneficial in the prevention of pouchitis after IPAA, especially in the short-term.


Research Progress and Hot Spot Analysis of the Propagation and Evolution Law of Prefabricated Cracks in Defective Rocks.
The generation of rock mass disasters in underground engineering essentially arises from the disruption of the original three-dimensional stress equilibrium of the rock mass caused by excavation and other activities, leading to the redistribution of stress fields. During the excavation process, the engineering rock mass undergoes complex dynamic stress equilibrium processes involving loading and unloading. This equilibrium process promotes the nucleation, initiation, and propagation of pre-existing cracks in the surrounding rock, resulting in changes in the internal structure of the rock mass and a weakening of its strength. Eventually, this localized cracking extends to global failure. In order to understand the current status better and study the development trends in the study of crack propagation and evolution in defective rock, this study conducts a bibliometric analysis of 288 articles from the Web of Science Core Collection database using CiteSpace software (version 6.1.R4). The results indicate an increasing trend in the annual publication output, characterized by two phases of emergence and rapid development. The countries of China, the United States, and Iran have the highest publication output in this field. The most frequently cited journals include INT J ROCK MECH MIN, ENG FRACT MECH, and ROCK MECH ROCK ENG. This study provides a comprehensive analysis of the current status and development trends in the research on the propagation and evolution of pre-existing cracks. This study enhances the comprehension of crucial aspects of crack propagation and evolution in rock materials with defects. Moreover, it opens up new possibilities for future investigations and holds promising implications for researchers and practitioners in the field.


Improving sensitivity of machine learning methods for automated case identification from free-text electronic medical records.
Distinguishing cases from non-cases in free-text electronic medical records is an important initial step in observational epidemiological studies, but manual record validation is time-consuming and cumbersome. We compared different approaches to develop an automatic case identification system with high sensitivity to assist manual annotators. We used four different machine-learning algorithms to build case identification systems for two data sets, one comprising hepatobiliary disease patients, the other acute renal failure patients. To improve the sensitivity of the systems, we varied the imbalance ratio between positive cases and negative cases using under- and over-sampling techniques, and applied cost-sensitive learning with various misclassification costs. For the hepatobiliary data set, we obtained a high sensitivity of 0.95 (on a par with manual annotators, as compared to 0.91 for a baseline classifier) with specificity 0.56. For the acute renal failure data set, sensitivity increased from 0.69 to 0.89, with specificity 0.59. Performance differences between the various machine-learning algorithms were not large. Classifiers performed best when trained on data sets with imbalance ratio below 10. We were able to achieve high sensitivity with moderate specificity for automatic case identification on two data sets of electronic medical records. Such a high-sensitive case identification system can be used as a pre-filter to significantly reduce the burden of manual record validation.


Clinical application of laparoscopic continuous interposition jejunostomy with double-tract anastomosis and esophagogastric anastomosis: a retrospective study.
The aim of this study was to compare the early clinical outcomes of laparoscopic-assisted proximal gastrectomy with continuous interposition of jejunal cis-peristaltic dual-channel anastomosis and esophagogastric anastomosis. A retrospective analysis of 130 patients who underwent laparoscopic-assisted radical resection of proximal gastric cancer in the Department of Gastrointestinal Surgery at the Affiliated Hospital of Chengde Medical College between June 2018 and October 2022 was conducted. Continuous interposition jejunal double-channel anastomosis (double-tract anastomosis) was used in 71 patients and esophagogastric anastomosis (esophagogastrostomy) in 59 patients. The basic clinical data, preoperative and postoperative clinical test indexes, postoperative complications and improvement of symptoms compared to preoperative ones, basic nutritional status and Visick classification of esophageal reflux symptoms at 6 months after surgery were compared between the two groups. Postoperative contrast images of patients in the continuous interposition jejunal double-tract group were collected and analyzed for the ratio of contrast agent remaining in the stomach to that remaining in the small intestinal channel. A total of 130 cases meeting the criteria were included in this study, including 71 cases involving the double-tract (DT) anastomosis method and 59 cases involving the esophagogastrostomy (EG) anastomosis method. There was no significant difference in preoperative information and perioperative safety between the two groups. Visick score of the DT group was significantly better than that of the EG group. Double-tract jejunal anastomosis can effectively improve esophageal reflux symptoms after proximal gastrectomy. At the same time, its anastomotic method also improves the nutritional status in the short term compared to the esophagogastric anastomosis and is a more ideal procedure for reconstructing the digestive tract after proximal gastrectomy.


Reliability of measuring hip and knee power and movement velocity in active youth.
The purpose of this study was to determine the reliability of measuring neuromuscular power and movement velocity of the hip and knee in young, active individuals using an isokinetic dynamometer. Peak power, average power, and peak velocity (PV) data were recorded for the hip in the standing position and the knee in the sitting position in 52 youth aged 10 to 14 years on 2 occasions approximately 1 week apart. The PV measures demonstrated the best absolute reliability of all variables tested (coefficients of variation of the typical error [CV(TE)] = 5.0%-8.5%; standard errors of measurement = 18.1-21.1°/s). Hip flexion and knee extension peak power and average power exhibited acceptable reliability (CV(TE) = 8.7%-10.8%) compared with the other isokinetic tests (CV(TE) = 16.9%-32.8%). Peak velocity appears to be a reliable means of indirectly measuring neuromuscular power in active youth, whereas direct measurement of power is only reliable for certain movements.


Poaceae pollen as the leading aeroallergen worldwide: A review.
The Poaceae family comprises over 12 000 wind-pollinated species, which release large amounts of pollen into the atmosphere. Poaceae pollen is currently regarded as the leading airborne biological pollutant and the chief cause of pollen allergy worldwide. Sensitization rates vary by country, and those variations are reviewed here. Grass pollen allergens are grouped according to their protein structure and function. In Poaceae, although species belonging to different subfamilies are characterized by distinct allergen subsets, there is a considerable degree of cross-reactivity between many species. Cross-reactivity between grass pollen protein and fresh fruit pan-allergens is associated with the appearance of food allergies. The additional influence of urban pollution may prompt a more severe immunological response. The timing and the intensity of the pollen season are governed by species genetics, but plant phenology is also influenced by climate; as a result, climate changes may affect airborne pollen concentrations. This article reviews the findings of worldwide research which has highlighted the major impact of climate change on plant phenology and also on the prevalence and severity of allergic disease.


Maternal exposure to prescription and non-prescription pharmaceuticals or drugs of abuse and risk of craniosynostosis.
The pre- and peri-natal drug exposures reported by women participating in a case-control study of children in Colorado were examined for association with infant craniosynostosis. Mothers of case and control children underwent a standardized telephone interview and obstetric and newborn medical record review. The interview included questions on the use of prescription and non-prescription drugs, nutritional supplements, recreational and drugs of abuse. The mother's obstetric record was abstracted for information about pharmacologic agents taken before and during the antepartum period. There were no statistically significant risk ratios associating craniosynostosis with prenatal exposure to hydantoin, valproic acid, or cocaine. Mothers of four case children and one control child reported specific exposure to retinoic acid. There were no statistically significant increases in the odds ratio (OR) for any suture type among children exposed to hypoxigenic agents, sympathomimetic or parasympatholytic agents, or metal-containing agents. The OR was 1.87 (lower bound of the two-sided 95% test-based confidence interval (CI): 1.08) among children with sagittal/lambdoid suture synostosis who were exposed to nitrosatable drugs chlorpheniramine, chlordiazepoxide, and nitrofurantoin compared to controls. Certain nitrosatable drugs may be associated with increased risk of infant sagittal/lambdoid craniosynostosis. A possible mechanism related to ischaemia/reperfusion injury is suggested.


Intestinal Mucormycosis in a Child With Maple Syrup Urine Disease After Orthotopic Liver Transplant.
Mucormycosis can result in serious morbidity and mortality, especially in transplant recipients. In this case report, we present a 3-year-old female patient with maple syrup urine disease who developed mucormycosis infection after deceased donor split liver transplant. Progressive segmental necrosis of the small intestines and new ischemic areas were observed after repeated abdominal surgeries. Microscopic examination of biopsy material revealed mucormycosis. Early recognition is crucial for treatment, and patients with clinical suspicion can be treated empirically with antifungal medicine. However, diagnostic tests with accurate and fast results are needed and more effective therapeutic methods should be developed for better outcomes.


[Involvement of myeloid derived immunosuppressive cells in progressive renal diseases].
Immunosuppressive cells have been reported to contribute to the inflammatory diseases in various organs. Interferon (IFN)-γ stimulations skew macrophages (Mψ) toward classically activated (M1) phenotype and interleukin (IL)-4, IL-13, IL-10 skew toward alternatively activated (M2) phenotypes. M2 polarized Mψ has immune regulatory function via various mechanisms, such as cytokine/chemokine expression, high activity of scavenging and interaction with other type of cells. Recently, another type of immunosuppressive myeloid cells, myeloid derived suppressor cells (MDSC), have been explored not only in tumor immunology, but also in inflammatory diseases. Orchestration of inflammation by these immunosuppressive cells with inflammatory cells has impact on progressive kidney diseases as well as inflammatory diseases.


Simple and novel icariin-loaded pro-glycymicelles as a functional food: physicochemical characteristics, in vitro biological activities, and in vivo experimental hyperlipidemia prevention evaluations.
A novel functional food for hyperlipidemia named icariin (ICA) pro-glycymicelles (ICA-PGs) using glycyrrhizin as a phytonanomaterial was easily prepared with improved storage, pH, and salt stabilities. ICA-PGs can easily dissolve in water to self-assemble into a clear glycymicelle solution with high ICA encapsulation efficiency. The ICA in ICA-PGs exhibits significantly increased aqueous solubility, faster in vitro release, and higher bioaccessibility than bare ICA. The ICA-PGs exhibited improved in vitro activities including antioxidant, anti-α-glucosidase, anti-lipase, and anti-cholesterol esterase activities. The ICA-PG also demonstrated improved antioxidant activity in cells. In vivo evaluation confirmed that the ICA-PG demonstrated a significant protective effect against experimental hyperlipidemia in mice, exhibiting decreasing levels of triglycerides (TGs), total cholesterol (TC), and low-density lipoprotein-cholesterol (LDL-C) in the serum, and restoring the hepatic morphology to the normal state. These results indicated that the ICA-PG could improve in vitro/in vivo profiles of ICA, providing a new concept and a promising functional food for hyperlipidemia.


Taxation and life expectancy in Western Europe.
With the exception of Denmark, life expectancy in Western Europe has shown a significant increase over the last decades. During that period of time overall taxation has increased in most of the countries, especially in Denmark. We, therefore, examined whether taxation could influence life expectancy in Western Europe. We used information on the sum of income tax and employees' social contribution in percentage of gross wage earnings from the OECD database and data on disability adjusted life expectancy at birth from the World Health Organization database. We arbitrarily only included countries with populations in excess of 4 millions and thereby excluded smaller countries where tax exemption is part of the national monetary policy. We found that disability adjusted life expectancy at birth was inversely correlated to the total tax burden in Western Europe. We speculate whether a threshold exists where high taxes exert a negative influence on life expectancy despite increased welfare spending. The study suggests that tax burden should be considered among the multiple factors influencing life expectancy.


In vitro effects on mobile polyethylene insert under highly demanding daily activities: stair climbing.
Wear and survival of total joint replacements do not depend on the duration of the implant in situ, but rather on the amount of its use, i.e. the patient's activity level. With this in mind, the present study was driven by two questions: (1) How does total knee replacement (TKR) respond to the simulation of daily highly demanding activities? (2) Are certain activities to be advised against or, on the contrary, useful to implanted patients, in order to reduce wear of TKR and its related problems? One set of the same total knee prosthesis (TKP), equal in design and size, was tested on a three-plus-one knee joint simulator for two million cycles using a highly demanding daily load waveform, replicating a stair-climbing movement. The results were compared with a set of TKP previously tested with the ISO level walking task. A digital microscope was used to characterise the superficial structure of all the TKPs. Gravimetric and micro-Raman spectroscopic analyses were carried out on the polyethylene inserts. Visual comparison with in vivo explants was carried out. The average volumetric mass loss after two million cycles was 44 ± 6 mm(3). Microscope examinations showed some deep scratches along the flexion/extension movements for all the components. Also, the metallic backside surface showed intense non-linear scratches and the polyethylene counterface was characterised by some craters. A decrease in crystallinity, induced by mechanical stress was observed on all polyethylene components and was quantitatively confirmed by the orthorhombic fraction αo value. The results of this study demonstrated that the forces and motion sustained by the knee are highly activity-dependent. Moreover, this test confirmed that under more severe conditions, the material properties change according to a different wear mechanism and a decrease in crystallinity occurs. Loading characteristics for specific activities should be considered for the design of functional and robust TKRs.


Inhibition of matrix metalloproteinases in gerbil cholesteatoma: preliminary findings.
This study was conducted to examine the role of matrix metalloproteinases (MMPs) and the impact of a topical MMP inhibitor, ilomostat, on the development of tympanic membrane (TM) atelectasis in the gerbil model. Eustachian tubes were cauterized bilaterally in 19 gerbils. Thereafter, both TMs received once-daily topical treatment for 8 weeks with ilomostat or vehicle or no treatment (n = 6 or 7 per group). TM atelectasis was serially graded, and TMs were harvested at 8 weeks. Gelatin zymograms were performed to determine MMP activity. The mean activity levels of proenzyme and active MMP-9 and MMP-2 and degree of atelectasis did not differ between groups. TM atelectasis did not correlate to levels of enzymes across individual samples. Topical application of an MMP inhibitor did not significantly prevent the development of TM atelectasis. It remains to be determined whether the use of MMP inhibitors may prevent the progression of atelectasis in humans.


The first coordination polymer of lanthanum(III) with a naphthalene-1,4,5,8-tetracarboxylic 1,8-anhydride derivative.
The title compound, catena-poly[[[heptaaqualanthanum(III)]-mu-1,3-dioxo-2-oxa-1H,3H-phenalene-6,7-dicarboxylato-kappa(2)O(6):O(7)] hemi(4,8-dicarboxynaphthalene-1,5-dicarboxylate) dihydrate], {[La(C(14)H(4)O(7))(H(2)O)(7)](C(14)H(6)O(8))(0.5).2H(2)O}(n), is a dihydrate of a coordination polymer between the dianion of naphthalene-1,4,5,8-tetracarboxylic 1,8-anhydride and the heptahydrated lanthanum(III) ion, charge balanced by an additional 4,8-dicarboxynaphthalene-1,5-dicarboxylate dianion that is located on an inversion centre and is not coordinated to the metal ion. The linear polymeric arrays adopt a comb-like structure, and these pack in pairs with one chain interpenetrating another, like two parts of a zip, to optimize stacking interactions between their ligand fragments. All the components of this compound are further interlinked by an extensive pattern of O-H...O hydrogen bonds throughout the crystal structure. The main scientific significance of the results reported here is that they demonstrate for the first time the feasibility of coordination polymerization of the above organic ligand with lanthanide ions. The resulting polymer has a unique architecture. Finally, the reported structure is a rare example where the tetraacid and the diacid anhydride ligand species co-exist in the same crystal.


Professionalism in pediatrics.
The purpose of this report is to provide a concrete overview of the ideal standards of behavior and professional practice to which pediatricians should aspire and by which students and residents can be evaluated. Recognizing that the ideal is not always achievable in the practical sense, this document details the key components of professionalism in pediatric practice with an emphasis on core professional values for which pediatricians should strive and that will serve as a moral compass needed to provide quality care for children and their families.


SABA Overuse in Russia - Burden and Possible Causes: An Analysis of the Russian Population in the SABINA III (SABA use IN Asthma) Study.
Short-acting β2-agonists (SABA) overuse is associated with asthma morbidity and mortality. The SABA use IN Asthma (SABINA) program aimed to describe the global use of SABA in patients with asthma. SABINA III study was a cross-sectional study covering 24 countries. We performed statistical analysis of the Russian population (618 patients recruited in 12 centers) from the SABINA III study. In this study in patients aged ≥12 years, data on disease characteristics and asthma treatments were collected using real-time electronic case report forms. Patients were classified by asthma severity and control according to the 2017 GINA. All variables (asthma severity and control, number of severe exacerbations, SABA and other medications use) were analyzed descriptively only, no hypothesis was tested. Majority of the study population consisted of patients with moderate/severe asthma (78.5%), while mild asthma was seen in 21.5%. Asthma was uncontrolled in 36.1% of patients and partly controlled in 33.5%. More than 80% of patients were treated with ICS/LABA fixed-dose combination. Almost half of all patients (47.0%) had at least 1 severe exacerbation in the previous 12 months. SABA over-prescription (≥3 canisters per year) was seen in 37% of patients. The frequency of SABA over-prescription was similar in patients with mild (35%) and moderate/severe (38%) asthma. SABA was purchased over-the-counter (OTC) in the past 12 months by 30.1% of all patients, and 14% purchased ≥3 canisters of SABA per year. About 91% of patients who purchased SABA OTC already received prescriptions for SABA, of whom 59% were prescribed ≥3 canisters per year. Russia is seeing very high level of SABA over-prescription. This is potentially associated with poor asthma control and frequent severe exacerbations. Over-prescription may serve as the main cause for SABA overuse in Russia. To reduce SABA overuse and improve overall asthma control in Russia, it is necessary to educate not just the patients but also the doctors, while actively implementing up-to-date asthma treatments.


Extensive Disturbances of Intracellular Components and Dysfunctions of Biological Pathways in the Brain Tissues During Prion Infection - China's Studies.
The study describes some of the major findings of changes in intracellular components and biological pathways in the brain during prion infection and hypothesizes some important physiological and pathological approaches mainly based on our studies. Omics techniques analysis of messenger RNA (mRNA) and proteins were carried out in the study. Meanwhile, Western blot, immunohistochemistry, and immunofluorescence were used for protein analysis in different signaling pathways. Statistical analyses were used to describe the protein differences in signaling pathways of infected and normal samples. This report reviewed and summarized our studies on the aberrant changes in intracellular components and biological functions in the brains of prion disease (PrD). Omics analyses proposed extensive abnormal alterations of brain mRNAs transcriptions, protein expressions, and post-translational modifications. The molecular disturbances for microtubule instability and depolymerization, the dysregulations of different signals related with neuron loss and synaptic plasticity, the abnormalities of mitochondrial and endoplasmic reticulum stress, and disturbance of intracellular reactive oxygen species homeostasis during prion infection were precisely analyzed and reviewed. Aberrant disturbances of numerous biological molecules and signals in brain tissues were found during prion infection.


Anatomical Description and Clinical Relevance of a Rare Variation in the Mesenteric Arterial Arcade Pattern.
Solitary vascular variations of the mesenteric arteries are extremely rare and have been seldom reported in the past. The aim of this study is to emphasize the anatomical and clinical relevance of one such rare variation of inferior mesenteric artery (IMA). The current case anomaly was incidentally observed while guiding the undergraduate medical students in the dissection of the mesenteric region of the abdomen in an Indian cadaver. An Accessory left colic artery was seen to be branching off from the Inferior Mesenteric artery and further dividing into two transverse branches which took part in the formation of arterial arc for the perfusion of the transverse and the descending colon. Awareness of such aberrant branches of Inferior Mesenteric artery helps in optimal selection of the mode of treatment or operative planning. Additionally, this knowledge minimizes possible iatrogenic injuries resulting from surgeries. Moreover, surgical anatomy of anomalous branches of Inferior Mesenteric artery is extremely essential for planning and successfully executing reconstructive procedures using these branches as pedicles for the transposed part of the colon.


Identification of endothelial progenitor cells in the corpus cavernosum in rats.
The vascular wall resident progenitor cells seem to serve as a local reservoir of cells for vascular repair. It was hypothesized that the corpus cavernosum may contain vascular wall endothelial progenitor cells (EPCs). In this study, we investigated the identification and localization of EPCs in the corpus cavernosum in a rat model. Adult male Sprague-Dawley rats were used to isolate EPCs from corpora cavernosum. To verify the existence and localization of EPCs, EPC-specific markers (CD34, Flk-1, and VE-cadherin) were evaluated by flow cytometric analysis and confocal microscopy. The EPC markers were mainly expressed in the cavernosal sinusoidal endothelial space. EPC-marker-positive cells made up about 3.31% of the corpus cavernosum of normal rat by FACS analysis. As shown by confocal microscopy, CD34+/Flk-1+ and CD34+/VE-cadherin+ positive cells existed in the corpus cavernosum. Our findings imply that regulation of corpus cavernosal EPCs may be a new therapeutic strategy in the treatment of erectile dysfunction.


Water wave collapses over quasi-one-dimensional nonuniformly periodic bed profiles.
Nonlinear water waves interacting with quasi-one-dimensional nonuniformly periodic bed profiles are studied numerically in the deep-water regime with the help of approximate equations for envelopes of the forward and backward waves. Spontaneous formation of localized two-dimensional wave structures is observed in the numerical experiments, which looks essentially as a wave collapse.


The role of sex and pregnancy in multiple sclerosis: what do we know and what should we do?
Multiple sclerosis (MS) is more prevalent in women than in men. The sex of the patient, and pregnancy, are reported to be associated with the clinical features of MS. The mechanism of this is unclear. This review summarizes data about sex differences in MS and the role of pregnancy. Possible mechanisms for the effects of sex and pregnancy are summarized, and practical suggestions for addressing these issues are provided. There is considerable interdependence of the variables that are associated with MS. Men have a worse outcome of MS, and this could be due to the same factors that lead to greater incidence of neurodegenerative disease in men. The possible role of parity on the long-term outcome of MS is of interest. Future studies that look at the mechanisms of the effects of the sex of the patient on the outcome of MS are required. However, there are some actions that can be taken without further research. We can concentrate on public health measures that address the modifiable risk factors for MS and ensure that disease is controlled in women who intend to become pregnant and use appropriate disease modifying agents during pregnancy.