Clinical signs of acute lower respiratory tract infections in malnourished infants and children.
To determine the reliability of respiratory rate and subcostal retractions in diagnosing acute lower respiratory infection (ALRI) in undernourished children. Three hundred twelve children with ALRI and 446 with upper respiratory infection were classified according to weight and height as normal, stunted, wasted or stunted and wasted and also as normal, underweight or marasmus. The sensitivity and specificity of tachypnea, subcostal retractions and the presence of either sign in identifying children with a clinical diagnosis of ALRI or radiologic pneumonia in each of the nutritional categories were determined and compared. Among children with ALRI the mean respiratory rate in those with normal nutrition (61.5 +/- 16.1, n = 160) was not significantly different from those who were stunted (57.5 +/- 16.5, n = 59), wasted (61.3 +/- 14, n = 66) or stunted and wasted (55.4 +/- 12.8, n = 27) (P > 0.05) or from those classified as underweight (60 +/- 15.9, n = 150) or marasmus (62.5 +/- 14.5, n = 27) (P > 0.4). The sensitivity and specificity of tachypnea, subcostal retraction or the presence of either sign in detecting ALRI was also not statistically significantly different among the children in the different nutritional categories (P > 0.05). The sensitivity of tachypnea or subcostal retraction in identifying children with radiologic pneumonia was also not significantly different among children in the different nutritional categories; the sensitivity of either sign was higher in under-weight children than in children with normal nutrition (P = 0.028). The data suggest that the current WHO algorithm is suitable for diagnosis of ALRI in undernourished children.


Extremely Low-Frequency Electromagnetic Fields Affect the miRNA-Mediated Regulation of Signaling Pathways in the GC-2 Cell Line.
Extremely low-frequency electromagnetic fields (ELF-EMFs) can affect male reproductive function, but the underlying mechanism of this effect remains unknown. miRNA-mediated regulation has been implicated as an important epigenetic mechanism for regulatory pathways. Herein, we profiled miRNA expression in response to ELF-EMFs in vitro. Mouse spermatocyte-derived GC-2 cells were intermittently exposed to a 50 Hz ELF-EMF for 72 h (5 min on/10 min off) at magnetic field intensities of 1 mT, 2 mT and 3 mT. Cell viability was assessed using the CCK-8 assay. Apoptosis and the cell cycle were analyzed with flow cytometry. miRNA expression was profiled using Affymetrix Mouse Genechip miRNA 3.0 arrays. Our data showed that the growth, apoptosis or cell cycle arrest of GC-2 cells exposed to the 50 Hz ELF-EMF did not significantly change. However, we identified a total of 55 miRNAs whose expression significantly changed compared with the sham group, including 19 differentially expressed miRNAs (7 miRNAs were upregulated, and 12 were downregulated) in the 1 mT exposure group and 36 (9 miRNAs were upregulated, and 27 were downregulated) in the 3 mT exposure group. The changes in the expression of 15 selected miRNAs measured by real-time PCR were consistent with the microarray results. A network analysis was used to predict core miRNAs and target genes, including miR-30e-5p, miR-210-5p, miR-196b-5p, miR-504-3p, miR-669c-5p and miR-455-3p. We found that these miRNAs were differentially expressed in response to different magnetic field intensities of ELF-EMFs. GO term and KEGG pathway annotation based on the miRNA expression profiling results showed that miRNAs may regulate circadian rhythms, cytokine-cytokine receptor interactions and the p53 signaling pathway. These results suggested that miRNAs could serve as potential biomarkers, and the miRNA-mediated regulation of signaling pathways might play significant roles in the biological effects of ELF-EMFs.


REVEALS: An Open Source Multi Camera GUI For Rodent Behavior Acquisition.
Understanding the rich behavioral data generated by mice is essential for deciphering the function of the healthy and diseased brain. However, the current landscape lacks effective, affordable, and accessible methods for acquiring such data, especially when employing multiple cameras simultaneously. We have developed REVEALS (Rodent BEhaVior Multi-camErA Laboratory AcquiSition), a graphical user interface (GUI) written in python for acquiring rodent behavioral data via commonly used USB3 cameras. REVEALS allows for user-friendly control of recording from one or multiple cameras simultaneously while streamlining the data acquisition process, enabling researchers to collect and analyze large datasets efficiently. We release this software package as a stand-alone, open-source framework for researchers to use and modify according to their needs. We describe the details of the GUI implementation, including the camera control software and the video recording functionality. We validate results demonstrating the GUI's stability, reliability, and accuracy for capturing and analyzing rodent behavior using DeepLabCut pose estimation in both an object and social interaction assay. REVEALS can also be incorporated into other custom pipelines to analyze complex behavior, such as MoSeq. In summary, REVEALS provides an interface for collecting behavioral data from one or multiple perspectives that, combined with deep learning algorithms, will allow the scientific community to discover and characterize complex behavioral phenotypes to understand brain function better.


Data-Driven Framework toward Accurate Prediction of Interfacial Thermal Resistance in Particulate-Filled Composites.
The interfacial thermal resistance (ITR) inside the particulate-filled polymer composite is a bottleneck for improving the thermal conductivity (TC) of the material. Getting full knowledge of the ITR is crucial to the material design as well as to a faithful prediction of TC of the composite. However, a method fully taking into account the local circumstances inside the composite is yet to be developed to precisely characterize the ITR. Here, we propose a comprehensive framework combining high-throughput numerical simulations, machine learning and optimization algorithms, and experiments, which is demonstrated to be robust for the accurate determination of ITRs inside the particulate-filled composites. The strategy extracts as much information as possible about the structure and heat transfer characteristics of the composite based on simple experiments, which lays the foundation for the method to be effective. We show that the polymer-filler ITRs and the effective filler-filler contact ITRs predicted with the method faithfully represent the true characteristics inside the composite materials; they also provide the exact effective parameters, which cannot be obtained from experiments, for accurate numerical prediction of TCs of composite materials with high efficiency. As a result, the framework not only provides a robust tool for accurate characterization of ITRs inside composites but also paves the way for virtual high-throughput formula screening of thermally conductive composite materials that could be used in industrial product design.


[The saphenous flap called the Acland's flap. Report of 2 cases].
The authors present two cases of Acland's flap. This flap described and published in 1981, is a very good flap, but the myocutaneous flaps have limited its use. However, the authors believe that there are indications for this saphenous flap. The vascular supply for this flap is a saphenous artery, the last branch of the femoral artery, before it becomes the popliteal artery. The authors report two cases: one neurovascular island flap for the posterior side of the knee, and the other case is a free flap for forearm. This flap is part of a particularly rich arterial network on the medial side of the thigh and of the knee. Masquelet, in 1986, showed that it is possible to raise a periosteal flap or a vascularized tendon flap.


Structural Characterization of Individual α-Synuclein Oligomers Formed at Different Stages of Protein Aggregation by Atomic Force Microscopy-Infrared Spectroscopy.
Aberrant α-synuclein aggregation is strongly associated with the onset and development of Parkinson's disease (PD). Therefore, characterizing the structure of toxic intermediate oligomers plays an essential role in better understanding their neurotoxicity. Using atomic force microscopy-infrared spectroscopy (AFM-IR), we were able to reveal the structure of α-synuclein oligomers present at different stages of protein aggregation and establish a relationship between morphology and structure on the single oligomer level. We were also able to probe the secondary structure evolution of individual oligomers. Moreover, the IR spectra of individual oligomers suggest structural rearrangement that is necessary for oligomers with an antiparallel β-sheet to propagate into fibrils that have a parallel-β-sheet secondary structure. Detailed investigation of structural organization of α-synuclein oligomers reported in this study is critically important to understand the toxicity of these protein species. We also anticipate that this work will help developing approaches for oligomer detection and consequently presymptomatic diagnostic of PD.


Comparison of prostatic acid phosphatase assays.
A prospective study compared five different assays for serum prostatic acid phosphatase in the detection of carcinoma of the prostate gland. The assays included two radioimmunoassay procedures, one counterimmunoelectrophoresis procedure, and an enzymatic procedure using alpha-naphthol phosphate substrate with and without sodium tartrate inhibition. The patients' hospital records were reviewed, as were all available surgical histology slides. The patients were divided into four groups: prostatic carcinoma, benign prostatic hypertrophy, other carcinomas (besides prostatic carcinoma), and no related disease states (that would be expected to give elevated acid phosphatase levels). The results were analyzed with respect to sensitivity, specificity, predictive value of a positive result, predictive value of a negative result, and efficiency of the assays.


Mechanisms of the cyclic nucleotide cross-talk signaling network in cardiac L-type calcium channel regulation.
Regulation of L-type Calcium (Ca2+) Channel (LCC) gating is critical to shaping the cardiac action potential (AP) and triggering the initiation of excitation-contraction (EC) coupling in cardiac myocytes. The cyclic nucleotide (cN) cross-talk signaling network, which encompasses the β-adrenergic and the Nitric Oxide (NO)/cGMP/Protein Kinase G (PKG) pathways and their interaction (cross-talk) through distinctively-regulated phosphodiesterase isoenzymes (PDEs), regulates LCC current via Protein Kinase A- (PKA) and PKG-mediated phosphorylation. Due to the tightly-coupled and intertwined biochemical reactions involved, it remains to be clarified how LCC gating is regulated by the signaling network from receptor to end target. In addition, the large number of EC coupling-related phosphorylation targets of PKA and PKG makes it difficult to quantify and isolate changes in L-type Ca2+ current (ICaL) responses regulated by the signaling network. We have developed a multi-scale, biophysically-detailed computational model of LCC regulation by the cN signaling network that is supported by experimental data. LCCs are modeled with functionally distinct PKA- and PKG-phosphorylation dependent gating modes. The model exhibits experimentally observed single channel characteristics, as well as whole-cell LCC currents upon activation of the cross-talk signaling network. Simulations show 1) redistribution of LCC gating modes explains changes in whole-cell current under various stimulation scenarios of the cN cross-talk network; 2) NO regulation occurs via potentiation of a gating mode characterized by prolonged closed times; and 3) due to compensatory actions of cross-talk and antagonizing functions of PKA- and PKG-mediated phosphorylation of LCCs, the effects of individual inhibitions of PDEs 2, 3, and 4 on ICaL are most pronounced at low levels of β-adrenergic stimulation. Simulations also delineate the contribution of the following two mechanisms to overall LCC regulation, which have otherwise been challenging to distinguish: 1) regulation of PKA and PKG activation via cN cross-talk (Mechanism 1); and 2) LCC interaction with activated PKA and PKG (Mechanism 2). These results provide insights into how cN signals transduced via the cN cross-talk signaling network are integrated via LCC regulation in the heart.


Estimating the parameters of background selection and selective sweeps in Drosophila in the presence of gene conversion.
We used whole-genome resequencing data from a population of Drosophila melanogaster to investigate the causes of the negative correlation between the within-population synonymous nucleotide site diversity (πS ) of a gene and its degree of divergence from related species at nonsynonymous nucleotide sites (KA ). By using the estimated distributions of mutational effects on fitness at nonsynonymous and UTR sites, we predicted the effects of background selection at sites within a gene on πS and found that these could account for only part of the observed correlation between πS and KA We developed a model of the effects of selective sweeps that included gene conversion as well as crossing over. We used this model to estimate the average strength of selection on positively selected mutations in coding sequences and in UTRs, as well as the proportions of new mutations that are selectively advantageous. Genes with high levels of selective constraint on nonsynonymous sites were found to have lower strengths of positive selection and lower proportions of advantageous mutations than genes with low levels of constraint. Overall, background selection and selective sweeps within a typical gene reduce its synonymous diversity to ∼75% of its value in the absence of selection, with larger reductions for genes with high KA Gene conversion has a major effect on the estimates of the parameters of positive selection, such that the estimated strength of selection on favorable mutations is greatly reduced if it is ignored.


A Morel-Lavallée lesion of the proximal calf in a young trauma patient: A case report.
The Morel-Lavallée lesion (MLL) is a closed degloving injury developing when shear force acts between the muscle fascia and the subcutaneous layer. MLLs develop principally in the trochanteric area or the pelvis; lesions in the proximal calf are rare. Acute lesions can be treated conservatively, but chronic lesions are best treated surgically because of a high rate of recurrence. To the best of our knowledge, this is a rare case of successful treatment of an MLL in the proximal calf associated with tibio-fibular shaft fracture. A 14-year-old male visited our emergency room after having been hit by a car. He exhibited direct trauma to the right lower leg and a distal tibio-fibular shaft fracture without an open wound. He underwent surgery to treat the fracture, which was immobilized with splint for 2 weeks post-operatively. At the 3-month follow-up, he complained of a painless, mobile, soft tissue mass in the posteromedial aspect of the proximal calf. Blood circulation was normal and we found no neurological abnormality in the distal region of the lower leg. A plain radiograph of the right lower leg revealed a proximal, round, radiopaque soft tissue lesion. Ultrasonography revealed a homogeneous, hypoechoic fluid collection. Magnetic resonance imaging revealed fluid of homogeneous signal intensity between the subcutaneous layer and the underlying fascia of the gastrocnemius muscle. Percutaneous drainage and intralesional steroid injection were performed on several occasions, but the lesion recurred every time. After 5 aspirations, we scheduled surgery. We radically excised the mass and sutured the superficial to the deep fascia to prevent shearing at the surgical plane. No complication or recurrence was noted at the 1-year follow-up. An MLL in the proximal calf is an uncommon post-traumatic lesion and care must be taken to avoid misdiagnosis. If an MLL is suspected after imaging studies and physical examination, it is important to determine whether the lesion is acute or chronic and to plan treatment accordingly. Appropriate treatment should be given to patients to improve outcomes.


Immunological characterization of two major proteins isolated from the outer membrane of Proteus mirabilis.
Two proteins with apparent molecular weights of 39,000 and 36,000 (M(r) 39,000 and M(r) 36,000, respectively) were isolated from the outer membrane of Proteus mirabilis 19. M(r) 36,000 was shown to be free of detectable amounts of the M(r) 39,000 protein by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and free of lipopolysaccharide according to gas chromatographic analyses of 3-hydroxymyristic acid content. The M(r) 39,000 protein contained no detectable amount of lipopolysaccharide and only a trace of M(r) 36,000. Both isolated proteins gave strong reactions in antisera produced to purified P. mirabilis 19 cell walls (outer membrane proteins in the native state). This suggested that the proteins isolated by our methods essentially retained their native configuration upon resolubilization. Antisera produced in rabbits to the isolated proteins showed strongest reactions with the homologous antigen, but some cross-reactions with the heterologous protein and with P. mirabilis 19 lipopolysaccharide were observed. These cross-reactions could be attributed to specific responses to traces of the heterologous (contaminant) proteins present in the purified proteins used as immunizing antigens. The M(r) 39,000 and M(r) 36,000 proteins have no major antigenic determinants in common. Reactions with P. mirabilis 19 lipopolysaccharide in antisera to the outer membrane proteins could be completely removed by absorption of the antisera with the M(r) 36,000 protein.


An alternative approach to the central circulation from above the diaphragm.
This is a review of a new fluoroscopically guided safe technique to place tunneled cuffed hemodialysis (HD) catheters via the supraclavicular location. Right supraclavicular catheters were placed in 12 patients who had no patent internal jugular veins. The placements were all successful and without serious complications. Over the 2 years of follow-up, two episodes of thrombosis/stenosis (16.7%) resulted in catheter removal. The rate of infection was 8%, or one episode in 1204 patient-days. The average length of use was 111 days. The average rate of blood flow was 354 cc/min. The right supraclavicular approach for tunneled HD catheters is safe and compares favorably to the internal jugular approach for patients with limited access options.


Effect of fibroblast growth factor on the division and fusion of bovine myoblasts.
The effect of fibroblast growth factor (FGF) on the rate of proliferation and fusion of bovine myoblast has been examined. Addition to the cultures of 0.1 mug-1 mug/ml of FGF stimulates the rate of proliferation and delays the fusion of primary cultures of bovine myoblasts cultured in 10% serum. Final cell densities reached in the presence of 0.1 mug/ml of FGF were fivefold higher than in controls; with 1 mug/ml, they were 10-fold higher. Increases in cell density were paralleled by increases in acetylcholine receptor sites as measured by the binding of 125I-alpha-bungarotoxin. Both fusion and the appearance of acetylcholine receptor sites were delayed in the presence of FGF. Growth hormone, insulin and testosterone, which have been reported to be mitogenic for rat and chick embryo myoblasts, did not have significant effects on DNA synthesis in bovine myoblasts when compared to the FGF. Conversely, FGF did not stimulate the proliferation of chick embryo myoblasts, indicating that it is not active in all vertebrate species.


Risk of tuberculosis in high-rise and high density dwellings: an exploratory spatial analysis.
Studies have shown that socioeconomic and environmental factors have direct/indirect influences on TB. This research focuses on TB prevalence of Hong Kong in relation to its compact urban development comprising of high-rise and high-density residential dwellings caused by rapid population growth and limited land resources. It has been postulated that occupants living on higher levels of a building would benefit from better ventilation and direct sunlight and thus less likely to contract infectious respiratory diseases. On the contrary, those on lower floors amid the dense clusters of high-rises are more susceptible to TB infection because of poorer air quality from street-level pollution and lesser exposure to direct sunlight. However, there have not been published studies to support these claims. As TB continues to threaten public health in Hong Kong, this study seeks to understand the effects of housing development on TB occurrences in an urban setting.


Withdrawal from cocaine self-administration and yoked cocaine delivery dysregulates glutamatergic mGlu5 and NMDA receptors in the rat brain.
In human addicts and in animal models, chronic cocaine use leads to numerous alterations in glutamatergic transmission, including its receptors. The present study focused on metabotropic glutamatergic receptors type 5 (mGluR(5)) and N-methyl-D-aspartate receptor subunits (NMDAR: GluN1, GluN2A, GluN2B) proteins during cocaine self-administration and after 10-day of extinction training in rats. To discriminate the contingent from the non-contingent cocaine delivery, we employed the "yoked"-triad control procedure. Protein expression in rat prefrontal cortex, nucleus accumbens, hippocampus, and dorsal striatum was determined. We also examined the Homer1b/c protein, a member of the postsynaptic density protein family that links NMDAR to mGluR(5). Our results revealed that cocaine self-administration selectively increased GluN1 and GluN2A subunit in the rat hippocampus and dorsal striatum, respectively, while mGluR(5) protein expression was similarly increased in the dorsal striatum of both experimental groups. Withdrawal from both contingent and non-contingent cocaine delivery induced parallel increases in prefrontal cortical GluN2A protein expression, hippocampal mGluR(5), and GluN1 protein expression as well as in accumbal GluN1 subunit expression, while the mGluR(5) expression was reduced in the prefrontal cortex. Extinction training in animals with a history of cocaine self-administration resulted in an elevation of the hippocampal GluN2A/GluN2B subunits and accumbal mGluR(5), and in a 50 % decrease of mGluR(5) protein expression in the dorsal striatum. The latter reduction was associated with Homer1b/1c protein level decrease. Our results showed that both contingent and non-contingent cocaine administration produces numerous, brain region specific, alterations in the mGluR(5), NMDA, and Homer1b/1c protein expression which are dependent on the modality of cocaine administration.


Multi-spectroscopic and molecular modelling studies on the interaction of esculetin with calf thymus DNA.
Understanding the interaction of small molecules with DNA has become an active research area at the interface between chemistry, molecular biology and medicine. Plant derived polyphenols possess diverse biological and pharmacological properties. Esculetin is a coumarin derivative polyphenolic compound having diverse pharmacological and therapeutic properties. However, its mode of interaction with DNA is still not well understood. In the present study, we have attempted to determine the mode of binding of esculetin with calf thymus DNA (Ct-DNA) through various biophysical techniques. Analysis of UV-visible absorbance spectra and fluorescence spectra indicates the formation of a complex between esculetin and Ct-DNA. The binding constant was found to be 1.87 × 10(4) M(-1). Thermodynamic parameters ΔG, ΔH, and ΔS at different temperatures indicated that hydrophobic interactions and hydrogen bonding played major roles in the binding process. Several other experiments such as iodide induced quenching and competitive displacement studies with ethidium bromide, acridine orange and Hoechst 33258 suggested that esculetin possibly binds to the minor groove of the Ct-DNA. The strong dependence on ionic strength in controlling the binding of esculetin with Ct-DNA confirms the possibility of electrostatic interaction. These observations were further supported by DNA melting studies, viscosity measurements, CD spectral analysis and in silico molecular docking.


Comparison between continuous subcutaneous insulin infusion and multiple insulin injection therapy in type 1 diabetes mellitus: 18-month follow-up.
To compare the results with continuous subcutaneous insulin infusion (CSII) versus multiple daily injections (MDI) of insulin in the treatment of type 1 diabetes during 18 months of follow-up. We prospectively studied 29 patients with type 1 diabetes in Brazil; 17 patients elected to change from conventional insulin therapy (2 injections daily) (N = 3) or MDI (N = 14) to CSII therapy, and the other 12 continued to receive MDI therapy. All patients were treated with insulin lispro; patients in the MDI treatment group also received NPH insulin. We compared hemoglobin A1c (HbA1c) values, determined at baseline and every 3 months, between the two treatment groups. Other variables analyzed included weight, body mass index, total daily dose of insulin, and incidence of severe hypoglycemia. Patients in the CSII group had a significant decrease (P<0.001) in mean HbA1c at 18 months in comparison with baseline (8.3% versus 6.5%). In the MDI group, no significant changes were found in mean HbA1c. After 3 months of treatment, patients in the CSII group had a significantly lower mean HbA1c level than did patients receiving MDI (P<0.05). Of the 17 patients treated with CSII, all had HbA1c values less than 7.5% at 18 months, and 13 (76%) had HbA1c levels less than 7%. Although no significant variations in weight were observed in either group, the insulin/weight ratio decreased in the CSII group from baseline to 18 months (0.8 U/kg to 0.6 U/kg; P = 0.02). No episodes of severe hypoglycemia were noted in either group. Patients with diabetes treated with insulin lispro have better glycemic control with CSII than with MDI. Most of our patients in the CSII group were able to achieve target HbA1c levels less than 7% at 18 months without an increase in hypoglycemic episodes.


Parent-to-parent support for parents with children who are deaf or hard of hearing: a conceptual framework.
Parent-to-parent support for parents with children who are deaf or hard of hearing (D/HH) is identified as an important component of Early Hearing Detection and Intervention (EHDI) programs for children with hearing loss. The specific aim of this review was to identify the constructs and components of parent-to-parent support for parents of children who are D/HH. An extensive scoping literature review identified 39 peer-reviewed articles published from 2000 to 2014. Studies were selected and reviewed based on standardized procedures. Data were identified, extracted, and organized into libraries of thematic and descriptive content. A conceptual framework of parent-to-parent support for parents of children who are D/HH was developed and presented in a comprehensive, bidirectional informational graphic. The constructs and components of the conceptual framework are (a) well-being: parent, family, and child; (b) knowledge: advocacy, system navigation, and education; and (c) empowerment: confidence and competence. The findings from this scoping review led to the development of a structured conceptual framework of parent-to-parent support for parents of children who are D/HH. The conceptual framework provides an important opportunity to explore and clearly define the vital contribution of parents in EHDI programs.


Uterine Primitive Neuroectodermal Tumor.
Uterine primitive neuroectodermal tumors (PNETs) are rare entities, with only around 70 cases published in the literature. Most of them are diagnosed in advanced stages with rapid progression and poor prognosis. Herein, we present a case of a 71-year-old patient with postmenopausal metrorrhagia and an ultrasound finding of endometrial thickening. The pathological diagnosis after an endometrial biopsy showed PNET. In the study of extension, possible distant dissemination with infiltration of the sigmoid and liver was observed. Chemotherapy treatment was proposed, but not begun due to the rapid progression of the disease. Four months after the initial diagnosis, the patient died of multiple organ failure. While there is no optimal chemotherapy treatment regimen for PNET, some studies have reported encouraging results. It is necessary to publish more studies emphasizing the follow-up and survival of the disease to establish which may be the best treatment option and thus improve the current poor prognosis.


Huddling by rat pups: ontogeny of individual and group behavior.
A full account of behavioral development in rats must include the ontogeny of both individual and group behavior. Most of our accumulated knowledge, however, pertains to individual ontogenesis. Group behavior and its development are readily seen in the huddling behavior of rat pups. A rat huddle is an entity with characteristics and capabilities distinct from those of the individuals that comprise it. The huddle is a natural context for acquiring olfactory preferences for species odors. Olfactory learning in a huddle involves thermal and tactile stimulation from the mother's body but, surprisingly, not the rewards of suckling or of milk transfer. Although there is complete developmental continuity of huddling behavior, the sensory controls of huddling change dramatically during the first 2 weeks of postnatal life. Huddling behavior is initially controlled by thermal cues ("physiological huddling") and then becomes dominated by olfactory stimuli ("filial huddling"). The complex group behavior of huddling was modeled successfully with computational methods. Group behavior emerges from individual interactions, guided entirely by rules of individual behavior (no rules for group behavior). Three simple rules of autonomous activity/inactivity can spawn the patterns of aggregon formation displayed by groups of 7-day-old pups, but not by 10-day-olds. The developmental change evident by Day 10 requires adding a rule by which each individual is affected by the activity state of adjacent pups. Group behavior responded to manipulations of central oxytocin on Day 10, but not on Day 7.


Mental health symptoms and their relationship to cannabis use in adolescents attending residential treatment.
The present study examined mental health symptoms and their relationship to cannabis use and treatment outcomes in a sample of adolescents who received treatment for cannabis dependence through a residential substance use program. The sample included 132 adolescents who nominated cannabis as their primary drug of concern upon admission and who completed at least 30 days of treatment. This study found that mental health symptoms of young cannabis users reduced significantly from admission to three-month follow-up. Further, pretreatment symptoms of anxiety were associated with greater pretreatment cannabis use, while symptoms of phobic anxiety were associated with less pretreatment cannabis use. Pretreatment obsessive-compulsive and somatization symptoms were associated with greater follow-up cannabis use, whereas pretreatment paranoid ideation symptoms were associated with less follow-up cannabis use. Further, follow-up somatization, obsessive-compulsive symptoms, hostility, and phobic anxiety were associated with greater follow-up cannabis use while follow-up symptoms of interpersonal sensitivity were associated with less follow-up cannabis use. These findings highlight a variety of areas for further investigation in order to enhance current treatment for cannabis use.


Porcine myelomonocytic markers and cell populations.
This review focuses in what is currently known about swine myeloid markers, the expression and function of these receptors in the biology of porcine myelomonocytic cells, the regulation of their expression along the different developmental stages of these cells and their utility to investigate the heterogeneity of monocyte and macrophage populations. Although the number of monoclonal antibodies recognizing surface antigens expressed on either swine granulocytes or monocytes is low compared with those available for human or mouse, they have contributed significantly to study the members of myeloid lineages in this species, allowing to discriminate different maturation stages of these cells in bone marrow and to reveal the heterogeneity of blood monocytes and tissue macrophages. Porcine myeloid cells share many similarities with humans, highlighting the relevance of the pig as a biomedical model.


Cellulose-based film modified by succinic anhydride for the controlled release of domperidone.
Succinic anhydride (SAD) modified microcrystalline cellulose (MCC) films was prepared and used for the controlled release of the drug domperidone (dom). The morphology and chemical structure of the modified materials were characterized by SEM, FTIR, XRD and TG/DSC techniques. The physical properties, such as water uptake and swelling, light barrier properties, mechanical testing, in vitro degradation behavior, have been investigated. Results showed that the modified cellulose membranes exhibited good anti-UV properties, higher water uptake values, improved mechanical capacity and anti-biodegradability. In addition, the modified MCC films (MS) as the drug carrier indicated the controlled release of domperidone and the release mechanism was proposed using Korsmeyer-Peppas equation at pH 7.4. The developed drug delivery system possessed the profound significance in improving pharmacodynamics and bioavailability of drugs.


[A case of brain metastasis from gastric cancer involving bilateral middle cerebellar peduncles].
A case with brain metastasis involving bilateral middle cerebellar peduncles (bMCP) was reported. A 71-year-old male with gastric cancer was treated for multiple brain metastasis by gamma knife radiosurgery (GKR) in September, 2004. Two months after the initial GKR, MRI showed asymmetrical enhanced lesions involving bMCP. A few months later, MRI revealed an expansional infiltration of bMCP lesions. The patient had presented with headache loss of appetite, cerebellar ataxia, diplopia and slight dysmetria. PET showed 2-deoxy-2- [18F] fluoro-D-glucose (FDG) uptake of the bMCP lesions. The lesions were diagnosed as brain metastasis of gastric cancer. The patient underwent his second GKR (marginal dose : 19Gy, maximum dose 38Gy) MRI revealed the disappearance of the tumors 3 months after the second GKR. One year later, the patient showed no evidence of recurrence. For the last time, our case was diagnosed as brain metastasis from gastric cancer without meningeal carcinomatosis. It was suggested that FDG-PET can provide additional information about the lesion of bMCP. GKR may be useful to treat the tumor in bMCP.


Gastric ischemic preconditioning may reduce the incidence and severity of anastomotic leakage after οesophagectomy: a systematic review and meta-analysis.
Anastomotic leakage after esophagectomy is a severe and life-threatening complication. Gastric ischemic preconditioning is a strategy for the improvement of anastomotic healing. Aim of this systematic review and meta-analysis is to investigate the impact of gastric ischemic preconditioning on postoperative morbidity. A systematic literature search was performed to identify studies comparing patients undergoing gastric ischemic preconditioning before esophagectomy with nonpreconditioned patients. Meta-analysis was conducted for the overall incidence of anastomotic leakage, severe anastomotic leakage, anastomotic stricture, postoperative morbidity, and mortality. Mantel-Haenszel odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed concerning preconditioning technique, the interval between preconditioning and surgery and the extent of preconditioning. Fifteen cohort studies were identified. Gastric preconditioning was associated with reduced overall incidence of anastomotic leakage (OR 0.73; 95% CI, 0.53-1.0; P = 0.050) and severe anastomotic leakage (OR 0.27; 95% CI, 0.14-0.50; P < 0.010), but not with anastomotic stricture (OR 1.18; 95% CI 0.38 to 3.66; P = 0.780), major postoperative morbidity (OR 1.03; 95% CI 0.45 to 2.36; P = 0.940) or mortality (OR 0.69; 95% CI 0.39 to 1,23; P = 0.210). Subgroup analyses did not identify any differences between embolization and ligation while increasing the interval between preconditioning and esophagectomy as well as the extent of preconditioning might be beneficial. Gastric ischemic preconditioning may be associated with a reduced incidence of overall and severe anastomotic leakage. Randomized studies are necessary to further evaluate its impact on leakage, refine the technique and define patient populations that will benefit the most.


The effectiveness of sexual assault nurse examiner (SANE) programs: a review of psychological, medical, legal, and community outcomes.
In sexual assault nurse examiner (SANE) programs, specially trained forensic nurses provide 24-hour-a-day, first-response medical care and crisis intervention to rape survivors in either hospitals or clinic settings. This article reviews the empirical literature regarding the effectiveness of SANE programs in five domains:(a) promoting the psychological recovery of survivors, (b) providing comprehensive and consistent post-rape medical care (e.g., emergency contraception, sexually transmitted disease [STD] prophylaxis), (c) documenting the forensic evidence of the crime completely and accurately, (d) improving the prosecution of sexual assault cases by providing better forensics and expert testimony, and (e) creating community change by bringing multiple service providers together to provide comprehensive care to rape survivors. Preliminary evidence suggests that SANE programs are effective in all domains, but such conclusions are tentative because most published studies have not included adequate methodological controls to rigorously test the effectiveness of SANE programs. Implications for practice and future research are discussed.


Bordetella type III secretion and adenylate cyclase toxin synergize to drive dendritic cells into a semimature state.
Bordetella bronchiseptica establishes persistent infection of the murine respiratory tract. We hypothesize that long-term colonization is mediated in part by bacteria-driven modulation of dendritic cells (DCs) leading to altered adaptive immune responses. Bone marrow-derived DCs (BMDCs) from C57BL/6 mice infected with live B. bronchiseptica exhibited high surface expression of MHCII, CD86, and CD80. However, B. bronchiseptica-infected BMDCs did not exhibit significant increases in CD40 surface expression and IL-12 secretion compared with BMDCs treated with heat-killed B. bronchiseptica. The B. bronchiseptica type III secretion system (TTSS) mediated the increase in MHCII, CD86, and CD80 surface expression, while the inhibition of CD40 and IL-12 expression was mediated by adenylate cyclase toxin (ACT). IL-6 secretion was independent of the TTSS and ACT. These phenotypic changes may result from differential regulation of MAPK signaling in DCs. Wild-type B. bronchiseptica activated the ERK 1/2 signaling pathway in a TTSS-dependent manner. Additionally, ACT was found to inhibit p38 signaling. These data suggest that B. bronchiseptica drive DC into a semimature phenotype by altering MAPK signaling. These semimature DCs may induce tolerogenic immune responses that allow the persistent colonization of B. bronchiseptica in the host respiratory tract.


[Study on dechlorination of p-chlorophenol by Ni/Fe bimetallic particles].
Dechlorination property of p-chlorophenol (p-CP) by Ni/Fe bimetallic particles was studied in this work. The experimental results show that adsorbed hydrogen atom is the main reductive agent for dechlorination of p-CP and chemical reaction at the surface of catalyst is the rate-determing step in this process. The catalyst with mass ratio of 2.96% Ni had the largest specific surface area and also had the highest dechlorination efficiencies (64% in 90 min) under the same conditions. The apparent kinetics of p-CP dechlorination by Ni/Fe was the first order reaction and apparent rate constant (kappa) was proportional to the specific surface of catalyst. The apparent rate constant per specific surface area (kappa') was also calculated (7.61 x 10(-4) min(-1) m(-2)). Temperature was also an important parameter in this system. The dechlorination efficiency was proportional to temperature when it is below 43 degrees C, when temperature exceeded 43 degrees C, increasing temperature had inverse effect on dechlorination efficiency.


Reticular theory versus neuron theory in the work of Camillo Golgi.
In 1873 Golgi invented a revolutionary method for microscopic research of the nervous system, based on a particular technique for staining nerve cells, which came to be known as "black reaction". Thanks to this method, he was able to provide a thorough and precise description of nerve cells in various regions of the cerebro-spinal axis, clearly distinguishing the axon from the dendrites. He drew up a new classification of cells on the basis of the structure of their nervous prolongation, and he criticized Gerlach's theory of the "protoplasmic network". Golgi claimed to observe in the gray matter an extremely dense and intricate network, composed of a web of intertwined branches of axons coming from different cell layers ("diffuse nervous network"). This structure, which emerges from the axons and is therefore essentially different from that hypothesized by Gerlach, appeared in his view to be the main organ of the nervous system, the organ that connected different cerebral areas both anatomically and functionally by means of the transmission of an electric nervous impulse. Golgi's reticular theory, along with the other reticular theories of the nervous system prevalent at the end of the nineteenth century, had in a certain sense overturned the 'atomistic-reductionist' principle that lay behind the cell theory. These theories were in fact based on a holistic model, according to which the cerebro-spinal axis was considered to be a continuous structure, and its functions the result of a collective action. At the end of the 1880's, Ramon y Cajal began to elaborate the neuron theory, using Golgi's microscopic technique. Golgi, however, did not accept this theory, and a controversy arose between the two scientists that was not put to rest even after the rivals were both awarded the Nobel Prize in 1906. If we look at the reasons for which Golgi opposed the neuron theory, we can see that they derived not so much from disagreement over the actual data observed, as from a different way of conceiving the anatomo-physiological architecture of the nervous system: Golgi appeared to support a holistic conception of the nervous system, the same that lay behind the theories of the opponents to cerebral localization, whereas Cajal and the 'neuronists' embraced an 'atomistic-reductionist' assumption, according to which the nervous system is made up of the sum of just so many neurons, each of which is an anatomical, functional, and embryological individuality, and not merely a <<transit station>> in a network of nervous filaments.


Intolerance of Uncertainty in Eating Disorders: A Systematic Review and Meta-Analysis.
Intolerance of uncertainty is an empirically supported transdiagnostic construct that may have relevance in understanding eating disorders. We conducted a meta-analysis and systematic review of intolerance of uncertainty in eating disorders using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We calculated random-effects standardised mean differences (SMD) for studies utilising the Intolerance of Uncertainty Scale (IUS) and summarised additional studies descriptively. Women with eating disorders have significantly higher IUS scores compared with healthy controls (SMD = 1.90; 95% C.I. 1.24 to 2.56; p < 0.001). Post hoc meta-analysis revealed significant differences when comparing women with anorexia nervosa with controls (SMD = 2.16; 95% C.I. 1.14 to 3.18; p < 0.001) and women with bulimia nervosa with controls (SMD = 2.03; 95% C.I. 1.30 to 2.75; p < 0.001). Our synthesis of findings suggests that intolerance of uncertainty may represent a vulnerability and maintenance factor for eating disorders and potential target of cognitive, behavioural, interoceptive and affective symptoms. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.


Radionuclide imaging in ischemic stroke.
Ischemic stroke is caused by interruption or significant impairment of blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphologic damage. The changes in regional cerebral blood flow and regional metabolism can be assessed by radionuclide imaging, especially SPECT and PET. SPECT and PET have broadened our understanding of flow and metabolic thresholds critical for maintenance of brain function and morphology: PET was essential in the transfer of the concept of the penumbra to clinical stroke and thereby had a great impact on developing treatment strategies. Receptor ligands can be applied as early markers of irreversible neuronal damage and can predict the size of the final infarcts, which is important for decisions on invasive therapy in large ("malignant") infarction. With SPECT and PET, the reserve capacity of the blood supply can be tested in obstructive arteriosclerosis, which is essential for planning interventions. The effect of a stroke on surrounding and contralateral primarily unaffected tissue can be investigated, helping to understand symptoms caused by disturbance in functional networks. Activation studies are useful to demonstrate alternative pathways to compensate for lesions and to test the effect of rehabilitative therapy. Radioisotope studies help to detect neuroinflammation and its effect on extension of tissue damage. Despite the limitations of broad clinical application of radionuclide imaging, this technology has a great impact on research in cerebrovascular diseases and still has various applications in the management of stroke.


Psychosocial perspectives of the partners of breast cancer patients treated with a mastectomy: an analysis of personal narratives.
The family members of cancer patients play a central role as caregivers. This study reports on the perspectives of men whose wives underwent a mastectomy because of breast cancer. This qualitative research used a narrative analysis method, and 17 men were interviewed. Five main themes emerged from the analysis of the narratives: initial reactions to the diagnosis, involvement in caregiving, support received, influence of breast cancer on the couples' relationships, and evaluation of care provided by the institution. The findings indicated the existence of substantive evidence that the spouses attended to and followed the recommendations of healthcare providers on ways to care for their wives, including their emotional demands and care needs. In this sense, the healthcare professionals should interact with a patient's primary caregiver, take the family dynamics and the caregiver's personal characteristics into account, and systematically consider and include the needs of the patients' caregivers in the entire healthcare process.


An Ultrasonic Rheometer to Measure Gas Absorption in Ionic Liquids: Design, Calibration and Testing.
The first goal of this study is to identify the ideal piezoelectric material for the manufacturing of rheological reflectance ultrasonic sensors. The second goal is to integrate the ultrasonic rheometer within a gas absorption reactor and to measure viscosity changes in an ionic liquid (IL) caused by gas absorption. To achieve the objectives, bismuth titanate, lead titanate, lead metaniobate and lead zirconate titanate materials in layer, tungsten bronze and perovskite structures were assembled on aluminum delay lines and tested under thermal cycling between room temperature and 150 °C. The results showed that lead metaniobate in tungsten bronze structure is the most suitable material for long time duration thermal cycling. Therefore, the ultrasonic rheometer was assembled using this material and installed in a pressurized reactor to test a reference IL at the operating conditions of 50 °C and at a pressure of 80 bar. The reference IL was saturated with nitrogen as well as hydrogen gas. Viscosity signals remained constant under the hydrogen atmosphere, while in nitrogen atmosphere the absorption of the gas lead to a rise in the value of viscosity.


An automatic glioma grading method based on multi-feature extraction and fusion.
An accurate assessment of tumor malignancy grade in the preoperative situation is important for clinical management. However, the manual grading of gliomas from MRIs is both a tiresome and time consuming task for radiologists. Thus, it is a priority to design an automatic and effective computer-aided diagnosis (CAD) tool to assist radiologists in grading gliomas. To design an automatic computer-aided diagnosis for grading gliomas using multi-sequence magnetic resonance imaging. The proposed method consists of two steps: (1) the features of high and low grade gliomas are extracted from multi-sequence magnetic resonance images, and (2) then, a KNN classifier is trained to grade the gliomas. In the feature extraction step, the intensity, volume, and local binary patterns (LBP) of the gliomas are extracted, and PCA is used to reduce the data dimension. The proposed "Intensity-Volume-LBP-PCA-KNN" method is validated on the MICCAI 2015 BraTS challenge dataset, and an average grade accuracy of 87.59% is obtained. The proposed method is an effective method for automatically grading gliomas and can be applied to real situations.


[Reproductive toxicity of male rats exposed to two isomers of bromopropanes].
To study the reproductive toxicity of male rats exposed to 1-bromopropane and 2-bromopropane and to explore the toxic mechanism of two isomers. 18 SPF SD male rats were randomly divided into 3 groups of 6 each, respectively. The groups were exposed to corn oil, 1-BP (1 g/kg) and 2-BP (1 g/ kg) for 7 days by intraperitoneally injection. Trait of reproductive organs, sperm characteristics, testicular histological and apoptotic findings and the lipid peroxidation in the testicular and epididymal tissue were determined. Results showed that treatment with bromopropanes induced reduction in sperm concentration and increments in abnormalities of sperm injuries to sperm quality. In addition, 1-BP increased GR activity (7. 42 +/- 2.98 vs. 4.25 +/- 1.18, P < 0.05) in testis, and SOD activity (91.87 +/- 3.93 vs. 80.59 +/- 9.92, P < 0.05) and MDA level (0.49 -/+ 0.20 vs. 0.39 +/- 0.08, P < 0.05) in epididymis. 2-BP decreased the GSH lever (6.35 +/- 1.86 vs. 10.89 +/- 3.69, P < 0.05) and increased the MDA level (0.42 +/- 0.07 vs. 0.24 +/- 0. 11, P < 0.05; 0.48 +/- 0.08 vs. 0.39 +/- 0.08, P < 0.05) in epididymis and testis, decreased GST ( 53.21 +/- 9.60 vs. 61.98 +/- 10.41, P < 0.05) and GR activity (2.48 +/- 1.21 vs. 7.75 +/- 8.56, P < 0.05) in epididymis. There were no histopathological changes in treatment with 1-BP rats, except that retained and elongated spermatids near basement membrane at the spermatogenesis cycle were found. Whereas, treatment with 2-BP induced vacuolation, degeneration and necrosis in seminiferous tubules. Paralleling with testicular lesion, treatment with 2-BP increased the total apoptotic cells per tubule, the percentage of apoptotic cells and apoptotic index significantly, comparing with control (17.72 +/- 4.59 vs. 5.92 +/- 1.05, P < 0.05; 0.34 +/- 0.14 vs. 0.10 +/- 0.02, P < 0.05; 6.64 +/- 3.40 vs. 0.59 +/- 0.20, P < 0.01). As compring with 1-BP group, exposed to 2-BP increased the percentages of TUNEL-positive tubules and apoptotic cellindex (0.34 +/- 0. 14 vs. 0.12 +/- 0. 03, P < 0.05; 6.64 +/- 3.40 vs. 0.76 +/- 0.21, P < 0.01). In addition, 2-BP group increased the proportion of apoptotic germ cells and the number of active caspase-3-positive cells per tubule, compared with 1-BP and control (P < 0.01, P < 0.01; P < 0.01, P < 0.01). This study indicates that bromopropanes can cause reproductive disorder in male rats, the rats treatment with 2-BP had more toxicity than that with 1-BP, and it might have different toxic mechanism between two isomers.


Psychostimulants and forced swim stress interaction: how activation of the hypothalamic-pituitary-adrenal axis and stress-induced hyperglycemia are affected.
We recently reported that simultaneous exposure to amphetamine and various stressors resulted in reduced hypothalamic-pituitary-adrenal (HPA) and glycemic responses to the stressors. Since this is a new and relevant phenomenon, we wanted to further explore this interaction. This study aims (i) to characterize the effect of various doses of amphetamine on the physiological response to a predominantly emotional stressor (forced swim) when the drug was given immediately before stress; (ii) to study if an interaction appears when the drug was given 30 min or 7 days before swim; and (iii) to know whether cocaine causes similar effects when given just before stress. Adult male rats were used and plasma levels of ACTH, corticosterone, and glucose were the outcomes. Amphetamine caused a dose-dependent activation of the HPA axis, but all doses reduced HPA and glycemic responses to swim when given just before the stressor. Importantly, during the post-swim period, the stressor potently inhibited the ACTH response to amphetamine, demonstrating mutual inhibition between the two stimuli. The highest dose of amphetamine also reduced the response to swim when given 30 min before stress, whereas it caused HPA sensitization when given 7 days before. Cocaine also reduced stress-induced HPA activation when given just before swim. The present results demonstrate a negative synergy between psychostimulants (amphetamine and cocaine) and stress regarding HPA and glucose responses when rats were exposed simultaneously to both stimuli. The inhibitory effect of amphetamine is also observed when given shortly before stress, but not some days before.


Prosthesis-patient mismatch after transcatheter aortic valve replacement: prevalence and medium term prognostic impact.
Prosthesis-patient mismatch (PPM) occurs when the effective orifice area of the prosthesis is too small in relation to the patient's body surface area. There are few data available on the frequency and prognostic impact of PPM after transcatheter aortic valve implantation (TAVI). Our aim was to determine the prevalence of PPM and to investigate its association with medium-term clinical course of patients undergoing TAVI. We included 185 patients undergoing TAVI (79 ± 5 years, 49% male, 98% CoreValve) between April-2008 and December-2014. The effective orifice area (EOA) was determined by transthoracic echocardiography prior and after the procedure. We defined PPM as indexed EOA ≤ 0.85 cm2/m2 (severe PPM if ≤ 0.65 cm2/m2). All cause death, stroke and hospitalization for heart failure were considered as major clinical events. 45 patients (24%) showed PPM (severe 11 patients, 6%). PPM was associated with a higher EuroSCORE (OR 1.06, IC 95% 1.01-1.12, p = 0.03), body surface area ≥ 1.72 m2 (OR 3.58, IC 95% 1.30-9.87, p = 0.01) and small aortic annulus (OR 0.73, IC 95% 0.55-0.92, p = 0.03); and severe PPM with small prostheses size (OR 17.79, IC 95% 1.87-169.78, p = 0.012). The mean event-free survival was 34 ± 26 months. Patients with severe PPM showed lower rates of event free survival than the rest of the series (52% vs. 84%, p = 0.04) at 34 months follow up. In our series, PPM was present in a quarter of the patients after TAVI. Higher EuroSCORE, smaller prosthesis size, larger body surface area and smaller aortic annulus diameter were associated with PPM. Severe PPM was an independent factor associated with major events at medium-term follow up.


Dexmedetomidine Preconditioning Protects Rats from Renal Ischemia-Reperfusion Injury Accompanied with Biphasic Changes of Nuclear Factor-Kappa B Signaling.
Acute kidney injury (AKI) is one of the most common and troublesome perioperative complications. Dexmedetomidine (DEX) is a potent α2-adrenoceptor (α2-AR) agonist with anti-inflammatory and renoprotective effects. In this study, a rat renal ischemia-reperfusion injury (IRI) model was induced. At 24 h after reperfusion, the IRI-induced damage and the renoprotection of DEX preconditioning were confirmed both biochemically and histologically. Changes in nuclear factor-kappa B (NF-κB), as well as its downstream anti-inflammatory factor A20 and proinflammatory factor tumor necrosis factor-α (TNF-α), were detected. Atipamezole, a nonselective antagonist, was then added 5 min before the administration of DEX to further analyze DEX's effects on NF-κB, and another anti-inflammatory medicine, methylprednisolone, was used in comparison with DEX, to further analyze DEX's effects on NF-κB. Different concentrations of DEX (0 nM, 0.1 nM, 1 nM, 10 nM, 100 nM, 1 μM, and 10 μM) were applied to preincubated human renal tubular epithelial cell line (HK-2) cells in vitro. After anoxia and reoxygenation, the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) tetrazolium assay and enzyme-linked immunosorbent assay (ELISA) were performed to evaluate the levels of NF-κB downstream anti-inflammatory cytokines. The results showed that, unlike methylprednisolone, DEX preconditioning led to a time-dependent biphasic change (first activation then inhibition) of NF-κB in the rat renal IRI models that were given 25 μg/kg i.p. It was accompanied by a similarly biphasic change of TNF-α and an early and persistent upregulation of A20. In vitro, DEX's cellular protection showed a concentration-dependent biphasic change which was protective within the range of 0 to 100 nM but became opposite when concentrations are greater than 1 μM. The changes in the A20 and NF-κB messenger RNA (mRNA) levels were consistent with the renoprotective ability of DEX. In other words, DEX preconditioning protected the rats from renal IRI via regulation biphasic change of NF-κB signaling.


Conjugated [5]Cumulene Polymers Enabled by Condensation Polymerization of Propargylic Electrophiles.
Cumulenes, sp-hybridized carbon motifs featuring consecutive double bonds, have rarely been explored as π-elements for conjugated polymers. Long cumulenic conjugated polymers can serve as models for approaching carbyne, an intriguing yet elusive carbon allotrope. However, their synthesis is notoriously difficult due to intrinsic instability. To date, only few [3]cumulene-based polymers have been synthesized, mostly relying on surface chemistry. Higher cumulene-based polymers remain unknown. Here, we present a "meet in the middle" strategy to overcome this challenge and synthesize high-molecular-weight, stable, and solution-processable conjugated [5]cumulene polymers (Mw up to 67.9 kg/mol). Our approach involves a new polymerization method called step-growth condensation polymerization of propargylic electrophiles (step-growth CPPE). The structures and molecular weights of the cumulenic polymers are established by various spectroscopic methods, including a comparative analysis of a discrete oligomer series. By introducing ortho-substituents on the aryl side groups, we successfully address the stability-conjugation dilemma. Electronic communication between cumulene units is found to be contingent upon the aromaticity of the π-spacers, enabling flexible energy-level adjustment and new narrow band gap polymers. The synthetic methodology and structure-property relationship established in this work serve as the starting points for the exploration of this fascinating family of sp-carbon-rich materials.


Bovine cells infected in vivo with Theileria annulata express CD11b, the C3bi complement receptor.
Bovine cells from cattle infected with Theileria annulata were phenotyped with monoclonal antibodies recognizing bovine leukocyte antigens. Macroschizont-infected, transformed cell lines prepared from peripheral blood mononuclear cells of cattle, infected with sporozoites, were assessed by flow cytometry; parasitized cells in tissues from infected cattle were examined by immunocytochemical techniques. Co-expression of markers for different cell lineages by the cell lines precluded a definite conclusion as to their phenotypic origins. For, while the pattern of leukocyte antigens expressed by these in vivo-derived schizont-infected cells, which included CD11b, was indicative of a myeloid origin, the possibility that they were NK cells could not be excluded. The monoclonal antibody (MAb) IL-A15, which recognizes CD11b, reacted with a high proportion of parasitized cells in sections of tissues from infected cattle at all stages of acute disease. Mononuclear cells infected with parasites at all stages of differentiation, from macroschizont to microschizont, expressed CD11b. Such parasitized cells occurred throughout the lymphoid tissues, being found in the thymus, spleen and lymph nodes, particularly the prescapular node draining the site of infection, the hepatic, mesenteric and precrural nodes, as well as in the reticulo-endothelial tissue of the liver, kidney, lung, abomasum, adrenal and pituitary glands. These observations provided the first evidence for a myeloid origin for the parasitized T. annulata cells found in infected bovine tissues and blood and suggested a mechanism whereby schizonts could transfer from cell to cell during mechanical infection with schizont-infected cells.


Renal vascular resistance in sickle cell painful crisis.
Vaso-occlusive painful crisis is one of the characteristic manifestations of sickle cell disease (SCD). We aimed to investigate the state of renal vascular resistance by means of Doppler ultrasonography during vaso-occlusive painful crisis in patients with SCD. The 60 patients with homozygous SCD who entered the study were divided into 2 groups. Group 1 included 45 patients who were living in steady-state conditions and had no history of transfusions within the 3 months before the initiation of the study. Group 2 consisted of 15 patients with signs of painful vaso-occlusive crisis during evaluation. Group 2 patients had significant reductions in 3 measures of flow velocity in both main renal arteries, compared with group 1 patients (P < .04, P < .001, and P < .01). Mean and end-diastolic velocities in the segmental arteries (P < .01, and P < .001, respectively) and end-diastolic velocities in the interlobar arteries (P < .04) were lower in group 2 patients than in group 1 patients. Analysis of resistive (RI) and pulsatile (PI) indices in the investigated arteries demonstrated that the RI of the renal (P < .001; P < .0001), segmental (P < .002; P < .0001) and interlobar (P < .001; P < .0001) arteries of both kidneys in group 2 < .0001; P < .0001) for both kidneys were markedly higher in group 2 patients than in group 1 patients and the healthy subjects, respectively. Our preliminary results suggest a reduction of renal blood flow and an increase in renal vascular resistance during painful crisis compared with steady-state SCD.


Evaluation of full vs. partial continuum of care in the treatment of publicly funded substance abusers in Washington State.
This study evaluated the relative effectiveness of two forms of publicly funded substance abuse treatment provided in Washington State: The full continuum (FC), in which clients receive approximately three weeks of inpatient treatment prior to outpatient care, and the partial continuum (PC), in which clients are admitted directly to outpatient treatment. Data on treatment process/proximal outcomes, such as psychological distress and readiness to change, were assessed at 8 weeks post intake, and data on treatment services received were obtained at 2, 4, 8, and 12 weeks. Multidimensional outcomes, including alcohol and drug use as well as a number of psychosocial functioning outcomes, were assessed at 3 and 9 months post intake. Results indicated that clients in the FC had greater alcohol, drug, and legal problem severity at intake than those in the PC, whereas medical and employment problem severity was greater in the PC. Clients in the FC received more treatment services in the first 2 weeks than those in the PC, but there were no differences at subsequent points. Outcome analyses at 3 and 9 months indicated that clients in the FC had greater improvements in alcohol, drug, and psychiatric severity than those in the PC. Matching analyses indicated that clients with greater substance-use severity at baseline improved to a greater degree in the FC as compared to the PC. Matching effects were not obtained with medical or psychiatric severity, or readiness to change.


Analysis of baculovirus IE1 in living cells: dynamics and spatial relationships to viral structural proteins.
IE1, a principal transcriptional activator of the baculovirus Bombyx mori nucleopolyhedrovirus (BmNPV), is an essential factor for viral DNA replication. During viral infection, IE1 accumulates in discrete subnuclear structures where viral DNA replication occurs. To analyse the dynamic properties of IE1, we monitored green fluorescent protein-tagged IE1 (IE1-GFP) in BmNPV-infected B. mori cells by live-cell microscopy. Time-lapse imaging showed that IE1-associated structures gradually expanded and occasionally fused with one another, while photobleaching experiments revealed that IE1-GFP was relatively immobile inside the IE1-associated structures. To investigate the spatial relationships between IE1 and viral structural proteins in infected cells, three GFP-tagged viral components were expressed together with DsRed-tagged IE1. Two structural proteins that constitute the occlusion-derived virus (ODV), P91-GFP and GFP-ODV-E25, localized to the periphery of the IE1-associated structures. While local accumulations of these proteins were often in contact with the IE1-associated structures, they did not extend beyond the boundaries of the structures. In contrast, the major capsid protein VP39-GFP predominantly accumulated within the IE1-associated structures. These data indicated, in conjunction with the finding of a high DNA content in the structures, that IE1 localizes to the virogenic stroma and therefore support the prediction previously proposed that the virogenic stroma is a site for viral DNA replication as well as for the assembly of nucleocapsids.


Ionophore A23187 induces acrosome reactions in sea urchin and guinea pig spermatozoa.
Ionophore A23187, in the presence of extracellular Ca+2, induces a morphologically normal acrosome reaction in sperm of the sea urchin and precocious acrosome reaction and activation of guinea pig sperm. Increased membrane permeability to Ca+2 is responsible for initiating the acrosome reaction in both sea urchin and guinea pig sperm. In sea urchin sperm, the permeability change is brought about by egg jelly, whereas in the guinea pig sperm it accompanies capacitation.


Stressors and rewards for workers in AIDS service organizations.
The primary objective of this study was to examine the impact of recent advances in the treatment of HIV/AIDS on AIDS service providers. The study surveyed the motivations, stressors, and rewards of workers employed in AIDS service organizations. Employees of AIDS service organizations play a valuable role in providing services to people with HIV/AIDS, and their motives and attitudes about their jobs are significantly related to the quality of care provided to clients. A total of 180 employees from nine AIDS service organizations in New York City completed a self-administered questionnaire. The questionnaire consisted of demographic, motivation, stressor, and reward items. This ethnically diverse sample consisted of social service workers (56%), administrative workers (22%), health care workers (18%), and other workers (4%). Forty-two percent of respondents had been working in the AIDS field for 5 or more years. The main reasons for choosing this line of work were a desire to help others, followed by having experienced the loss of a loved one to AIDS. Overall, respondents rated the level of stressors in their jobs as moderate. The main category of stress was "lack of support" (referring to the availability of resources and support for clients). The most important individual stressors were societal attitudes towards AIDS, salary, client deaths, and administrative duties. The most highly valued reward factor associated with AIDS caregiving was "personal effectiveness." Overall, the rewards of AIDS caregiving outweighed the stressors, for respondents. Implications of these findings for administrators of AIDS service organizations are discussed.


One-Year Efficacy and Safety of 0.1% Cyclosporine a Cationic Emulsion in the Treatment of Severe Dry Eye Disease.
The SANSIKA study evaluated the efficacy/safety of 0.1% (1 mg/mL) cyclosporine A cationic emulsion (CsA CE) for treating dry eye disease (DED) with severe keratitis. The double-masked phase demonstrated that CsA CE was effective in reducing corneal damage and ocular surface inflammation, and was well-tolerated over 6 months. Here we report efficacy and safety findings of SANSIKA's open-label extension (OLE). In this multicenter, double-masked, phase III study, patients with severe DED (corneal fluorescein staining [CFS] grade 4, modified Oxford scale) were randomized to once-daily CsA CE (Ikervis®) or its vehicle for 6 months, followed by 6-month open-label, once-daily CsA CE (CsA CE/CsA CE and vehicle/CsA CE groups). A total of 177 patients completed the OLE. Efficacy results reiterated the double-masked phase: CsA CE reduced CFS score and human leukocyte antigen-antigen D related expression, improved corneal clearing, and produced continuous improvements in global symptom scores (ocular surface disease index [OSDI], visual analogue scale). The CFS-OSDI response rates (≥2 CFS points, ≥30% OSDI improvement vs baseline) at 12 vs 6 months were 39.1% vs 28.6%, respectively, for CsA CE/CsA CE and 38.0% vs 23.1% for vehicle/CsA CE. Cyclosporine A CE's safety profile was similar to the initial 6 months. The most common treatment-related treatment-emergent adverse event was instillation site pain (7.8%, CsA CE/CsA CE group; 19.0%, vehicle/CsA CE group). No unexpected safety signals were observed; systemic CsA levels were undetectable/negligible in all patients except 2 previously treated with systemic CsA. In this 12-month study, once-daily CsA CE was well-tolerated and showed reductions in ocular surface inflammation and improvements in signs/symptoms in DED patients with severe keratitis.


Epigenetics in teleost fish: From molecular mechanisms to physiological phenotypes.
While the field of epigenetics is increasingly recognized to contribute to the emergence of phenotypes in mammalian research models across different developmental and generational timescales, the comparative biology of epigenetics in the large and physiologically diverse vertebrate infraclass of teleost fish remains comparatively understudied. The cypriniform zebrafish and the salmoniform rainbow trout and Atlantic salmon represent two especially important teleost orders, because they offer the unique possibility to comparatively investigate the role of epigenetic regulation in 3R and 4R duplicated genomes. In addition to their sequenced genomes, these teleost species are well-characterized model species for development and physiology, and therefore allow for an investigation of the role of epigenetic modifications in the emergence of physiological phenotypes during an organism's lifespan and in subsequent generations. This review aims firstly to describe the evolution of the repertoire of genes involved in key molecular epigenetic pathways including histone modifications, DNA methylation and microRNAs in zebrafish, rainbow trout, and Atlantic salmon, and secondly, to discuss recent advances in research highlighting a role for molecular epigenetics in shaping physiological phenotypes in these and other teleost models. Finally, by discussing themes and current limitations of the emerging field of teleost epigenetics from both theoretical and technical points of view, we will highlight future research needs and discuss how epigenetics will not only help address basic research questions in comparative teleost physiology, but also inform translational research including aquaculture, aquatic toxicology, and human disease.


Be alert to the alterations in the biological characteristics in heterogeneous vancomycin-intermediate Staphylococcus aureus.
The development of reduced vancomycin susceptibility in Staphylococcus aureus in many cases appears to be associated with characteristic changes. These changes may have pitfall of identifying S. aureus by automated testing methods like Vitek 32. In this study, we retested 24 heterogeneous vancomycin-intermediate Staphylococcus haemolyticus (h-VISH) collected in 2008-2010 at the Department of Clinical Microbiology by conventional biochemical tests and polymerase chain reaction (PCR). The heterogeneous vancomycin-intermediate S. aureus (hVISA) reversion test and electron microscopic examination were also used. Six isolates of 24 h-VISH possessed nuc, coa, and 16S rRNA genes, and could be reversed into S. aureus. It suggested that biochemical and morphological changes in hVISA and vancomycin-intermediate S. aureus (VISA) should be considered, and the detection of S. aureus, especially reduced vancomycin susceptibility isolates, requires more attention and different techniques.


Adapting the International Dysphagia Diet Standardisation Initiative in East Asia: Feasibility study.
In dysphagia, food or water cannot be delivered safely through the oral cavity to the stomach; both are treated using texture-modified food and thickened fluid. Before, each country had its own diet modifications and texture measurement standards. In 2012, the International Dysphagia Diet Standardisation Initiative (IDDSI) was developed by several countries. Owing to cultural differences, it was necessary to determine whether the IDDSI could well be applied to clinicians and patients without difficulties in East Asia countries. To evaluate the IDDSI scale to find out the difficulties applying this scale in East Asia countries to educate the clinicians and patients. In May 2021, we enrolled physicians, nurses, nutritionists, and swallowing therapists involved in dysphagia treatment at a single center in Seoul. To evaluate the degree of understanding and difficulties of adapting IDDSI to clinicians in East Asia countries, we used the 17-item questionnaire with IDDSI sample foods and foods in Asian countries. In first 7 items, we compared IDDSI with the previously used scale based on the National Dysphagia Diet (NDD). In the next 10 questions, only the IDDSI levels were answered, and the absolute values of the answer-response differences were calculated. The IDDSI showed a significantly high intraclass correlation with the previously used NDD-based scale; the coefficient was higher for the nutritionists (0.988) and swallowing therapists (0.991). When evaluating whether the IDDSI could applied well in East Asia countries, the absolute values of the answer-response differences were lower than 0.5 in majority of levels, except for Level 4. Because the IDDSI framework might successfully be applied universally regardless of food culture, a worldwide standard for food rheology in dysphagia treatment might be possible.


COVID-19 incidence and mortality in non-dialysis chronic kidney disease patients.
Many studies reported a higher risk of COVID-19 disease among patients on dialysis or with kidney transplantation, and the poor outcome of COVID-19 in these patients. Patients in conservative management for chronic kidney disease (CKD) have received attention only recently, therefore less is known about how COVID-19 affects this population. The aim of this study was to provide evidence on COVID-19 incidence and mortality in CKD patients followed up in an integrated healthcare program and in the population living in the same catchment area. The study population included CKD patients recruited in the Emilia-Romagna Prevention of Progressive Renal Insufficiency (PIRP) project, followed up in the 4 nephrology units (Ravenna, Forlì, Cesena and Rimini) of the Romagna Local Health Authority (Italy) and alive at 1.01.2020. We estimated the incidence of COVID-19, its related mortality and the excess mortality within this PIRP cohort as of 31.07.2020. COVID-19 incidence in CKD patients was 4.09% (193/4,716 patients), while in the general population it was 0.46% (5,195/1,125,574). The crude mortality rate among CKD patients with COVID-19 was 44.6% (86/193), compared to 4.7% (215/4,523) in CKD patients without COVID-19. The excess mortality of March-April 2020 was +69.8% than the average mortality of March-April 2015-19 in the PIRP cohort. In a cohort mostly including regularly followed up CKD patients, the incidence of COVID-19 among CKD patients was strongly related to the spread of the infection in the community, while its lethality is associated with the underlying kidney condition and comorbidities. COVID-19 related mortality was about ten times higher than that of CKD patients without COVID. For this reason, it is urgent to offer a direct protection to CKD patients by prioritizing their vaccination.


Possible hereditary Y-chromosome instability.
A 9 year old boy, born to a phenotypically normal, non-consanguineous couple was referred for clinical examination due to radio-ulnar synostosis. We made cytogenetic analyses to investigate the genotype-phenotype correlation. Chromosomal studies on the boy and his father revealed a very small Y chromosome in both cases, probably due to loss of the heterochromatic long arm segment. Repeated cytogenetic analysis of the boy was made, using QFQ, CBG, DA/DAPI and fluorescence in situ hybridization (FISH) methods with DYZ1 and DYZ3 probes. The results showed a likely mosaicism of cell lines with either a small Y or a normal Y found in the boy. The small Y appeared to be composed of double centromeric regions, without the heterochromatic segment of the long arm of the Y chromosome. The father refused re-analysis. These findings indicate an inherent instability of the Y chromosome resulting in a familial small Y. The radio-ulnar synostosis may be associated with excessive Y short arms.


The relationship of the Functional Rating Index with disability, pain, and quality of life in patients with low back pain.
The study was planned to determine the relationship of the Functional Rating Index (FRI) with disability, pain, and quality of life in patients with low back pain. A total of 84 patients with low back pain, of whom 58 were women and 26 were men, with average age of 47.8 +/- 12.0 years participated in this study. The Functional Rating Index was used to determine the functional status of the patients. Disability was evaluated using the Roland-Morris Disability Questionnaire (RMQ), pain intensity was evaluated with the Visual Analog Scale (VAS), and the Short Form-36 (SF-36) was used to assess quality of life. The Pearson correlation coefficient was used for correlation of the FRI with the RMQ, VAS, and SF-36. The internal consistency for test-retest reproducibility of FRI was assessed with Cronbach's alpha. There was a strong positive correlation between the FRI and the RMQ (p < 0.05). It was found that an increase in severity of pain was associated with the FRI survey score (p < 0.05). There was a negative statistically significant correlation between the FRI and all parameters of SF-36 (p < 0.05). FRI demonstrated high internal consistency, with alpha = 0.960. The test-retest correlation was r = 0.926 (p = 0.000). Our study reveals that the FRI, as a reliable instrument in assessing functional status, is associated with the RMQ, the VAS, and all items of the SF-36 in patients with LBP. It was concluded that changes in functional status were related to changes in disability, pain, and quality of life.


Molecular Binding Mechanism of TtgR Repressor to Antibiotics and Antimicrobials.
A disturbing phenomenon in contemporary medicine is the prevalence of multidrug-resistant pathogenic bacteria. Efflux pumps contribute strongly to this antimicrobial drug resistance, which leads to the subsequent failure of clinical treatments. The TtgR protein of Pseudomonas putida is a HTH-type transcriptional repressor that controls expression of the TtgABC efflux pump, which is the main contributor to resistance against several antimicrobials and toxic compounds in this microbe. One of the main strategies to modulate the bacterial resistance is the rational modification of the ligand binding target site. We report the design and characterization of four mutants-TtgRS77A, TtgRE78A, TtgRN110A and TtgRH114A - at the active ligand binding site. The biophysical characterization of the mutants, in the presence and in the absence of different antimicrobials, revealed that TtgRN110A is the variant with highest thermal stability, under any of the experimental conditions tested. EMSA experiments also showed a different dissociation pattern from the operator for TtgRN110A, in the presence of several antimicrobials, making it a key residue in the TtgR protein repression mechanism of the TtgABC efflux pump. We found that TtgRE78A stability is the most affected upon effector binding. We also probe that one mutation at the C-terminal half of helix-α4, TtgRS77A, provokes a severe protein structure distortion, demonstrating the important role of this residue in the overall protein structure and on the ligand binding site. The data provide new information and deepen the understanding of the TtgR-effector binding mechanism and consequently the TtgABC efflux pump regulation mechanism in Pseudomonas putida.


Scales for measuring health belief model dimensions: a test of predictive value, internal consistency, and relationships among beliefs.
Critiques of research on the Health Belief Model have been directed at the need for: (1) applying the Model to behavior related to chronic illness; (2) multivariate testing of the major dimensions of the Model; (3) developing reliable scales; and (4) explicating the relationships among the beliefs. In an attempt to respond to these concerns, data are presented from a prospective study of mothers' adherence to a diet regimen prescribed for their obese children. The Model components were found, both singly and in combination, to be correlated with the study's measure of dietary compliance. Multiple regression analysis utilizing five belief indices accounted for a substantial portion of the variance in children's weight change. Questionnaire items employed in creating indices for each Model dimension are presented, together with discussion of the internal consistency of each index. Belief intercorrelations appear to demonstrate that distinct Model dimensions exist.


Biochemistry of cancer procoagulant.
Cancer procoagulant (CP), EC188.8.131.52, is a cysteine proteinase produced by malignant or fetal tissue. It is a single chain Mr 68 kDa protein containing no carbohydrates. Prevalent amino acids are Ser (19.15), Gly (18.7%), Glu (12.5%), Lys (8.1%) and Asp (7.1%). Amino-acid sequence of CP is not determined yet. The natural substrates for CP are coagulation factor X and probably PAR-1 receptor. However, the peptidyl bond in factor X molecule hydrolyzed by CP is different from the bond recognized by other known FX-activators. Peptidyl chromogenic substrates hydrolyzed by CP are those with Pro at P2 and Arg or Lys at P1 position. Factor X-activating activity of CP is inhibited by number of various inhibitors: peptidyl diazomethyl ketones. iodoacetamide, mercuric chloride, PMSF, leupeptin and antipain. It has been demonstrated that E-64, a specific inhibitor of cysteine proteinases, inhibits CP reversible acting as a competitive inhibitor of the enzyme. The CP activity is modulated by the presence of divalent metal ions in the reaction environment. Ca2+, Cd2+, Mg2+ and Mn2+ ions potentiate the procoagulant activity when Cu2+, Fe2+, Sn2+ and Zn2+ ions inactivate CP.


Pseudogap in cuprates in the loop-current ordered state.
Scanning tunneling microscopy (STM) has revealed that the magnitude of the pseudo-gap in under-doped cuprates varies spatially and is correlated with disorder. The loop-current order, characterized by the anapole vector Ω, discovered in under-doped cuprates occurs in the same region of the temperature and doping as the pseudo gap observed in STM and ARPES experiments. Since translational symmetry remains unchanged in the pure limit, no gap occurs at the chemical potential. On the other hand for disorder coupling linearly to the different possible orientations of Ω, there can only be a finite temperature dependent static correlation length for the loop-current state at any temperature. This leads to formation of domains of the ordered state with different orientation and magnitude of Ω in each. For the characteristic size of the domains much larger than the Fermi-vectors [Formula: see text], the boundary of the domains leads to forward scattering of the Fermions. Such forward scattering is shown to push states near the chemical potential to energies both above and below it leading to a pseudo-gap with an angular dependence which is maximum in the [Formula: see text] directions because the single-particle energies are degenerate in these directions for all domains. The magnitude of the average gap systematically increases with the square of the average loop order parameter measured by polarized neutron scattering. This result is tested. A unique result of the gap due to forward scattering is the lack of a bump in the density of states at the 'edge' of the pseudo-gap so that the depletion of states near the chemical potential is recovered only in integration up to the edge of the band. This is also in agreement with a variety of experiments. Some predictions for further experiments are provided. Due to the finite correlation length, low frequency excitations are expected at long wavelength at all temperatures in the 'ordered' phase. Such fluctuations motionally average over the shifts in frequencies of local probes such as NMR and muon resonance expected for a truly static order.


Experimental observation of quantum correlations in four-wave mixing with a conical pump.
Generation of multimode quantum states has drawn much attention recently due to its importance for both fundamental science and the future development of quantum technologies. Here, by using a four-wave mixing process with a conical pump beam, we have experimentally observed about -3.8 dB of intensity-difference squeezing between a single-axial probe beam and a conical conjugate beam. The multi-spatial-mode nature of the generated quantum-correlated beams has been shown by comparing the variation tendencies of the intensity-difference noise of the probe and conjugate beams under global attenuation and local cutting attenuation. Due to its compactness, phase-insensitive nature, and easy scalability, our scheme may find potential applications in quantum imaging, quantum information processing, and quantum metrology.


miR-508 Defines the Stem-like/Mesenchymal Subtype in Colorectal Cancer.
Colorectal cancer includes an invasive stem-like/mesenchymal subtype, but its genetic drivers, functional, and clinical relevance are uncharacterized. Here we report the definition of an altered miRNA signature defining this subtype that includes a major genomic loss of miR-508. Mechanistic investigations showed that this miRNA affected the expression of cadherin CDH1 and the transcription factors ZEB1, SALL4, and BMI1. Loss of miR-508 in colorectal cancer was associated with upregulation of the novel hypoxia-induced long noncoding RNA AK000053. Ectopic expression of miR-508 in colorectal cancer cells blunted epithelial-to-mesenchymal transition (EMT), stemness, migration, and invasive capacity in vitro and in vivo In clinical colorectal cancer specimens, expression of miR-508 negatively correlated with stemness and EMT-associated gene expression and positively correlated with patient survival. Overall, our results showed that miR-508 is a key functional determinant of the stem-like/mesenchymal colorectal cancer subtype and a candidate therapeutic target for its treatment.Significance: These results define a key functional determinant of a stem-like/mesenchymal subtype of colorectal cancers and a candidate therapeutic target for its treatment. Cancer Res; 78(7); 1751-65. ©2018 AACR.


Comparative Effectiveness of Clinical-Community Childhood Obesity Interventions: A Randomized Clinical Trial.
Novel approaches to care delivery that leverage clinical and community resources could improve body mass index (BMI) and family-centered outcomes. To examine the extent to which 2 clinical-community interventions improved child BMI z score and health-related quality of life, as well as parental resource empowerment in the Connect for Health Trial. This 2-arm, blinded, randomized clinical trial was conducted from June 2014 through March 2016, with measures at baseline and 1 year after randomization. This intent-to-treat analysis included 721 children ages 2 to 12 years with BMI in the 85th or greater percentile from 6 primary care practices in Massachusetts. Children were randomized to 1 of 2 arms: (1) enhanced primary care (eg, flagging of children with BMI ≥ 85th percentile, clinical decision support tools for pediatric weight management, parent educational materials, a Neighborhood Resource Guide, and monthly text messages) or (2) enhanced primary care plus contextually tailored, individual health coaching (twice-weekly text messages and telephone or video contacts every other month) to support behavior change and linkage of families to neighborhood resources. One-year changes in age- and sex-specific BMI z score, child health-related quality of life measured by the Pediatric Quality of Life 4.0, and parental resource empowerment. At 1 year, we obtained BMI z scores from 664 children (92%) and family-centered outcomes from 657 parents (91%). The baseline mean (SD) age was 8.0 (3.0) years; 35% were white (n = 252), 33.3% were black (n = 240), 21.8% were Hispanic (n = 157), and 9.9% were of another race/ethnicity (n = 71). In the enhanced primary care group, adjusted mean (SD) BMI z score was 1.91 (0.56) at baseline and 1.85 (0.58) at 1 year, an improvement of -0.06 BMI z score units (95% CI, -0.10 to -0.02) from baseline to 1 year. In the enhanced primary care plus coaching group, the adjusted mean (SD) BMI z score was 1.87 (0.56) at baseline and 1.79 (0.58) at 1 year, an improvement of -0.09 BMI z score units (95% CI, -0.13 to -0.05). However, there was no significant difference between the 2 intervention arms (difference, -0.02; 95% CI, -0.08 to 0.03; P = .39). Both intervention arms led to improved parental resource empowerment: 0.29 units (95% CI, 0.22 to 0.35) higher in the enhanced primary care group and 0.22 units (95% CI, 0.15 to 0.28) higher in the enhanced primary care plus coaching group. Parents in the enhanced primary care plus coaching group, but not in the enhanced care alone group, reported improvements in their child's health-related quality of life (1.53 units; 95% CI, 0.51 to 2.56). However, there were no significant differences between the intervention arms in either parental resource empowerment (0.07 units; 95% CI, -0.02 to 0.16) or child health-related quality of life (0.89 units; 95% CI, -0.56 to 2.33). Two interventions that included a package of high-quality clinical care for obesity and linkages to community resources resulted in improved family-centered outcomes for childhood obesity and improvements in child BMI. clinicaltrials.gov Identifier: NCT02124460.


Enantioselective component selection in multicomponent supramolecular gels.
We investigate a two-component acid-amine gelation system in which chirality plays a vital role. A carboxylic acid based on a second generation l-lysine dendron interacts with chiral amines and subsequently assembles into supramolecular gel fibers. The chirality of the amine controls the assembly of the resulting diastereomeric complexes, even if this chirality is relatively "poor quality". Importantly, the selective incorporation of one enantiomer of an amine over the other into the gel network has been demonstrated, with the R amine that forms complexes which assemble into the most stable gel being primarily selected for incorporation. Thermodynamic control has been proven by forming a gel exclusively with an S amine, allowing the R enantiomer to diffuse through the gel network, and displacing it from the "solidlike" fibers, demonstrating that these gels adapt and evolve in response to chemical stimuli to which they are exposed. Excess amine, which remains unincorporated within the solidlike gel fiber network, can diffuse out and be reacted with an isocyanate, allowing us to quantify the enantioselectivity of component selection but also demonstrating how gels can act as selective reservoirs of potential reagents, releasing them on demand to undergo further reactions; hence, component-selective gel assembly can be coupled with controlled reactivity.


Mechanically induced intramolecular electron transfer in a mixed-valence molecular shuttle.
The kinetics and thermodynamics of intramolecular electron transfer (IET) can be subjected to redox control in a bistable [2]rotaxane comprised of a dumbbell component containing an electron-rich 1,5-dioxynaphthalene (DNP) unit and an electron-poor phenylene-bridged bipyridinium (P-BIPY(2+)) unit and a cyclobis (paraquat-p-phenylene) (CBPQT(4+)) ring component. The [2]rotaxane exists in the ground-state co-conformation (GSCC) wherein the CBPQT(4+) ring encircles the DNP unit. Reduction of the CBPQT(4+) leads to the CBPQT(2(•+)) diradical dication while the P-BIPY(2+) unit is reduced to its P-BIPY(•+) radical cation. A radical-state co-conformation (RSCC) results from movement of the CBPQT(2(•+)) ring along the dumbbell to surround the P-BIPY(•+) unit. This shuttling event induces IET to occur between the pyridinium redox centers of the P-BIPY(•+) unit, a property which is absent between these redox centers in the free dumbbell and in the 1:1 complex formed between the CBPQT(2(•+)) ring and the radical cation of methyl-phenylene-viologen (MPV(•+)). Using electron paramagnetic resonance (EPR) spectroscopy, the process of IET was investigated by monitoring the line broadening at varying temperatures and determining the rate constant (k(ET) = 1.33 x 10(7) s(-1)) and activation energy (ΔG(‡) = 1.01 kcal mol(-1)) for electron transfer. These values were compared to the corresponding values predicted, using the optical absorption spectra and Marcus-Hush theory.


An 8-gene machine learning model improves clinical prediction of severe dengue progression.
Each year 3-6 million people develop life-threatening severe dengue (SD). Clinical warning signs for SD manifest late in the disease course and are nonspecific, leading to missed cases and excess hospital burden. Better SD prognostics are urgently needed. We integrated 11 public datasets profiling the blood transcriptome of 365 dengue patients of all ages and from seven countries, encompassing biological, clinical, and technical heterogeneity. We performed an iterative multi-cohort analysis to identify differentially expressed genes (DEGs) between non-severe patients and SD progressors. Using only these DEGs, we trained an XGBoost machine learning model on public data to predict progression to SD. All model parameters were "locked" prior to validation in an independent, prospectively enrolled cohort of 377 dengue patients in Colombia. We measured expression of the DEGs in whole blood samples collected upon presentation, prior to SD progression. We then compared the accuracy of the locked XGBoost model and clinical warning signs in predicting SD. We identified eight SD-associated DEGs in the public datasets and built an 8-gene XGBoost model that accurately predicted SD progression in the independent validation cohort with 86.4% (95% CI 68.2-100) sensitivity and 79.7% (95% CI 75.5-83.9) specificity. Given the 5.8% proportion of SD cases in this cohort, the 8-gene model had a positive and negative predictive value (PPV and NPV) of 20.9% (95% CI 16.7-25.6) and 99.0% (95% CI 97.7-100.0), respectively. Compared to clinical warning signs at presentation, which had 77.3% (95% CI 58.3-94.1) sensitivity and 39.7% (95% CI 34.7-44.9) specificity, the 8-gene model led to an 80% reduction in the number needed to predict (NNP) from 25.4 to 5.0. Importantly, the 8-gene model accurately predicted subsequent SD in the first three days post-fever onset and up to three days prior to SD progression. The 8-gene XGBoost model, trained on heterogeneous public datasets, accurately predicted progression to SD in a large, independent, prospective cohort, including during the early febrile stage when SD prediction remains clinically difficult. The model has potential to be translated to a point-of-care prognostic assay to reduce dengue morbidity and mortality without overwhelming limited healthcare resources.


Neocondyle distraction osteogenesis in the management of temporomandibular joint ankylosis: Report of five cases with review of literature.
Management of temporomandibular joint (TMJ) ankylosis is a challenging and rather daunting task owing to complex abnormal anatomy and its sequel to craniofacial structures. Various autogenous grafts and alloplastic materials have been tried with variable success for creation of a near-normal joint. In recent years, neocondyle distraction has added a new dimension to the management of TMJ ankylosis. The aim of this paper is to describe the role of neocondyle distraction in TMJ ankylosis. Neocondyle distraction was carried out in five patients with TMJ ankylosis following gap arthroplasty. Computed tomogram scans were taken before surgery and 1-year postdistraction for surgical planning and postoperative assessment, respectively. The intraoral distractors (KLS Martin, Jacksonville, FL, USA) were used in this study. All five patients reported with adequate mouth opening and functional jaw movements. The procedure was well tolerated by all the patients. None of the patients underwent reankylosis following neocondyle distraction. With proper surgical planning and distraction protocol, neocondyle distraction is an effective and safe technique for TMJ reconstruction and preventing reankylosis.