Is histological diagnosis of neuronal intestinal dysplasia related to clinical and manometric findings in constipated children? Results of a pilot study.
Neuronal intestinal dysplasia (NID) of the colon has been reported in adults and children with chronic constipation. However, it is unknown whether these histological abnormalities are related to the severity of symptomatology or the findings of anorectal manometry. We studied 57 children (2 weeks to 17 years old, 33 boys) who had chronic constipation and/or soiling or obstructive symptoms early in life and evaluated anamnestic data, symptoms, outcome after 6 months of conventional therapy, rectal biopsies for signs of dysganglionosis, and results of anorectal manometry. In cooperative patients, defectaion dynamics were recorded during manometry with simultaneous surface electromyogram of the external anal sphincter. In 30 older patients, severity of constipation was assessed by measurement of colonic transit time with radiopaque markers. Histology confirmed Hirschsprung's disease in nine (excluded from further analysis), hyperganglionosis of the plexus submucosus (classic NID) in six, heterotopic ganglion cells without hyperganglionosis (abortive NID) in 18, and no signs of dysganglionosis in 24 patients. The rectoanal inhibitory reflex was more often absent or abnormal in children with classic NID (six of six) and abortive NID (11 of 17) compared with children with normal histology (four of 22) (p < 0.001). All other manometric parameters analyzed, colonic transit times, and clinical outcomes were not related to histological diagnosis. In contrast, the severity of constipation and outcome was significantly worse in children with abnormal defecation dynamics. These results suggest that histological signs of NID in the submucous plexus are of uncertain value in assessing the clinical picture and should not influence decisions concerning further treatment, especially surgical interventions.


Novel Blood-Based Biomarkers of Cognition, Stress, and Physical or Cognitive Training in Older Adults at Risk of Dementia: Preliminary Evidence for a Role of BDNF, Irisin, and the Kynurenine Pathway.
Psychosocial stress and physical, cognitive, and social activity predict the risk of cognitive decline and dementia. The aim of this study was to elucidate brain-derived neurotrophic factor (BDNF), irisin, and the kynurenine pathway (KP) as potential underlying biological correlates. We evaluated associations of irisin and the KP with BDNF in serum and with cognition, stress, and activities. Furthermore, changes in serum concentrations of BDNF, irisin, and KP metabolites were investigated after physical or cognitive training. Forty-seven older adults at risk of dementia were assigned to 10 weeks of physical training, cognitive training, or a wait-list control condition. Previous physical, cognitive, and social activities and stressful life events were recorded; global cognition, episodic memory, and executive functions were assessed. Serum levels of L-kynurenine, kynurenic acid, 3-hydroxykynurenine (3-HK), and quinolinic acid (QUIN) were determined by validated assays based on liquid chromatography coupled to tandem mass spectrometry. BDNF and irisin serum levels were determined with enzyme-linked immunosorbent assays. BDNF and irisin correlated positively with global cognition and episodic memory, while the neurotoxic metabolite QUIN correlated negatively with executive functions. Stressful life events were associated with reduced BDNF and increased 3-HK. 3-HK decreased after cognitive training, while BDNF tended to increase after physical training. This suggests that psychosocial stress as well as cognitive and physical training may impact BDNF serum levels and the KP. Irisin and QUIN may constitute novel serum biomarkers of cognitive impairment, in addition to BDNF. Larger scale trials are needed to replicate and extend these novel findings.


Mean nuclear volume in cervical intraepithelial neoplasia and carcinoma.
To correlate three-dimensional nuclear size (mean nuclear volume) estimated by the stereologic intercept methodfor objective classification of cervical intraepithelial neoplasia (CIN) and carcinoma. In this retrospective study a total number of 29 CIN cases (8 cases of CIN 1, 10 cases of CIN 2 and 11 cases of CIN 3) and 10 cervical squamous cell carcinoma cases were selected. Mean nuclear volume (MNV) of all cases was measured with an image cytometer (Leica, Cambridge, England) using Quantimet 600 software (Leica). Nuclear point resection method was adopted to measure nuclear volume. Mean intercepted diameter of at least 50 nuclei was measured randomly. MNV was correlated with the histologic grade and diagnosis. MNV of CIN 1, 2, 3 and carcinoma cases was 291.72, 403.33, 711.45 and 893 microm3, respectively. ANOVA test results showed that MNV of CIN 1 and 2 was significantly lower than that of CIN 3 and invasive carcinoma (P < .000). MNV of CIN 3 was also significantly lower than that of carcinoma cases (P <.05). The findings suggest that estimates of MNV on conventional histopathology slides provide objective and useful criteria for relatively subjective histopathologic grading.


Nonenzymic translocation and spontaneous release of noncognate peptidyl transfer ribonucleic acid from Escherichia coli ribosomes.
Poly(uridylic acid)-programmed ribosomes have been used to synthesize the noncognate peptidyl-tRNA Ac-Phe-Tyr-tRNATyr and its cognate counterpart Ac(Phe)2-tRNAPhe. After synthesis, Ac(Phe)2-tRNAPhe remains, as expected, in the ribosomal acceptor (A) site, but the noncognate AcPhe-Tyr-tRNATyr does not; part of it spontaneously falls off the ribosome and the rest translocates, without elongation factor (EF) G, to the ribosomal donor site. The inhibitor of translocation viomycin prevents both the spontaneous release and the nonenzymatic translocation by confining the noncognate peptidyl-tRNA to the A site. Under these conditions, the interaction of AcPhe-Tyr-tRNATyr with the A site appears to be similar to that of Ac(Phe)2-tRNAPhe without the antibiotic, and EF-G promotes the translocation and subsequent elongation of both peptidyl-tRNAs to comparable extents. The results indicate that, without viomycin, the noncognate peptidyl-tRNA is weakly held in the ribosomal A site and support the proposal that the release of peptidyl-tRNA occurring during protein synthesis in vivo is related to a ribosomal editing mechanism which discards mistranslated nascent proteins [Menninger, J. R. (1977) Mech. Ageing Dev. 6, 131].


An improved characterization of goat chromosomes by means of G- and R-band comparison.
An improved characterization of goat (Capra hircus, 2n = 60) chromosomes was obtained after a G- and R-banding comparison of the prometaphase chromosomes arranged according to the standard karyotype. GTG-, GBG-, RBG, and RBA-banding made possible construction of G- and R-banded idiograms with a common banding nomenclature. A brief G- and R-banding description of chromosomes 4, 6, 22, 23, 25, 27, 28 and 29 is also given.


Androgen abuse epidemiology.
To systematically review current epidemiological literature on androgen abuse. Estimates from 32 empirical epidemiological articles were reviewed. Generally, androgen abuse epidemiology and prevalence is higher in Europe, the Middle East, North America (the USA), Oceania (Australia and New Zealand), and South America (Brazil) and lower in Africa and Asia. In contrast to the general population, androgen abuse epidemiology and prevalence is higher among athletes, injection drug users, recreational sportspeople, and sexual and gender minorities. From the 1970s, androgen abuse spread from athletes into the general population. Consistent with previous evidence, reviewed studies suggest that androgen abuse epidemiology and prevalence is higher in Western cultural contexts, the Middle East, and South America (Brazil) and lower in Africa and Asia. Evidence also corroborates indications that androgen abuse is less prevalent among women (vs. men), and in the general population in contrast to particular subpopulations consisting of athletes, injection drug users, recreational sportspeople, and sexual and gender minorities. Adolescents' androgen abuse should be of special concern. Androgen abuse in some nonsports occupations (e.g. security workers) requires further exploration. Polypharmacy and the Internet proliferation of androgens and other PIEDs require surveillance for prevention and harm reduction.


Majority group belonging without minority group distancing? Minority experiences of intergroup contact and inequality.
As most immigrant-origin minority youth grow up in ethnically diverse social worlds, they develop a sense of belonging to both the national majority and the ethnic minority group. Our study adds to a growing body of research on minority experiences of intergroup contact by (1) including both minority and majority group belonging as outcomes and (2) examining the interplay of majority contact with unequal treatment. We surveyed 1,200 Turkish and Moroccan-Belgian minority youth in 315 classrooms across 65 schools, using multiple measures of intergroup contact, unequal treatment in school, and minority and majority group belonging. Multi-level models showed that minority youth who experienced more intergroup contact, and less unequal treatment, reported more belonging to the majority group. In addition, contact predicted less belonging to the minority group only in the presence of unequal treatment: For minority youth who perceived less unequal treatment, either individually or collectively, intergroup contact was unrelated to minority group belonging. We conclude that majority group contact and belonging need not come at the cost of minority group distancing in the absence of inequality.


Ceramide lipids in alive and thermally stressed mussels: an investigation by hydrophilic interaction liquid chromatography-electrospray ionization Fourier transform mass spectrometry.
Hydrophilic interaction liquid chromatography coupled to electrospray ionization-Fourier transform mass spectrometry was employed to study ceramide lipids occurring in mussels of sp. Mytilus galloprovincialis. Lipid extracts from alive mussels and mussels deliberately subjected to specific thermal treatments were analyzed. In particular, single and tandem MS measurements were performed on a hybrid quadrupole-Orbitrap mass spectrometer and then complemented by MS(n) analyses (n = 2, 3) achieved by a linear ion trap mass spectrometer. This approach enabled the characterization of 66 ceramide lipids, encompassing ceramide phosphoethanolamines (CPE), ceramide aminoethylphosphonates (CAEP) and N-monomethylated CAEP. The sphingoid and acyl chains of each ceramide lipid could be distinctly recognized in terms of numbers of carbon atoms and C=C bonds, and indications on the possible location of the latter on the sphingoid chain could be often inferred from fragmentation patterns. The occurrence of several species hydroxylated on the α carbon of the acyl chain was also discovered. On the other hand, the sphingoid chain of ceramide lipids was never found to be involved in oxidation processes, unless forced exposure of the mussel lipid extracts to atmospheric oxygen was performed. CPE(d19:3/16:0) and its hydroxylated form, CPE(d19:3/2-OH-16:0), were found to be the prevailing species among CPE, whereas CAEP(d18:2/16:0), CAEP(d19:3/16:0) and CAEP(d19:3/2-OH-16:0) were the most abundant CAEP. Finally, ceramide lipids showed a remarkably higher stability, compared with glycerophospholipids, in mussels subjected to different thermal treatments. This finding opens interesting perspectives on the role of ceramide-based lipids in the adaptation of aquatic organisms to thermal stresses. Copyright © 2016 John Wiley & Sons, Ltd.


Immunologically mediated disease of the airways after pulmonary transplantation.
Obliterative bronchiolitis has occurred in eleven of 30 recipients of cardiopulmonary allografts who survived at least 4 months after transplantation, has caused significant morbidity, and has been associated with four of eleven late deaths in this series. Although some improvement, or at least stability, of pulmonary function has followed augmented immune suppression, it appears that once the process is recognized clinically, much of the damage to the airways is irreversible. The histopathology, response to therapy, and, most important, the response of donor specific alloreactivity in the lymphocytes from the lung (bronchoalveolar lavage and peripheral blood) suggest immune- mediated basis for bronchiolitis obliterans. The presence of donor specific alloreactivity detected by primed lymphocyte testing predicted obliterative bronchiolitis in five of six recipients (83% sensitivity, 91% specificity) was absent in ten of eleven recipients who have not as yet developed the process (negative predicted value of 91%). Currently, the presence of a positive primed lymphocyte test in the bronchoalveolar lavage of the cardiopulmonary recipient is an indication for early treatment by augmented immune suppression.


Hemostatic analysis of a 13 year old with antiphospholipid syndrome and restrictive pericarditis.
Antiphospholipid syndrome is an autoimmune thrombophilic disorder that is uncommon in adults and remarkably rare in children. Thrombotic etiological factors are variable in antiphospholipid syndrome, including antibody-antigen complex-mediated platelet activation, inhibition of anticoagulants, or attenuation of fibrinolysis. We present the case of a child with antiphospholipid syndrome presenting with syncope, constrictive pericarditis and hepatic enlargement that was found to have platelet-mediated hypercoagulability and marked clot lysis via thrombelastography in the preoperative period. Restoration of circulation following pericardectomy and inotropic support was associated with attenuation of hypercoagulability and fibrinolysis. It is concluded that the etiological factors responsible for antiphospholipid syndrome-mediated hemostatic abnormalities and the probable effects of hepatic hypoperfusion on clot lysis in this patient were detected with thrombelastography, and similar thrombelastographic analyses are recommended to compliment standard coagulation assessments of patients with antiphospholipid syndrome.


Additive manufacturing leveraged microfluidic setup for sample to answer colorimetric detection of pathogens.
Colorimetric readout for the detection of infectious diseases is gaining traction at the point of care/need owing to its ease of analysis and interpretation, and integration potential with highly specific loop-mediated amplification (LAMP) assays. However, coupling colorimetric readout with LAMP is rife with challenges including, rapidity, inter-user variability, colorimetric signal quantification, and user involvement in sequential steps of the LAMP assay, hindering its application. To address these challenges, for the first time, we propose a remotely smartphone-operated automated setup consisting of (i) an additively manufactured microfluidic cartridge, (ii) a portable reflected-light imaging setup with controlled epi-illumination (PRICE) module, and (iii) a control and data analysis module. The microfluidic cartridge facilitates sample collection, lysis, mixing of amplification reagents stored on-chip, and subsequent isothermal heating for initiation of amplification in a novel way by employing tunable elastomeric chambers and auxiliary components (heaters and linear actuators). PRICE offers a new imaging setup that captures the colorimetric change of the amplification media over a plasmonic nanostructured substrate in a controlled and noise-free environment for rapid minute-scale nucleic acid detection. The control and data analysis module employs microprocessors to automate cartridge operation in tandem with the imaging module. The different device components were characterized individually and finally, as a proof of concept, SARS-CoV-2 wild-type RNA was detected with a turnaround time of 13 minutes, showing the device's clinical feasibility. The suggested automated device can be adopted in future iterations for other detection and molecular assays that require sequential fluid handling steps.


Construction of a gammaretrovirus with a novel tropism and wild-type replication kinetics capable of using human APJ as entry receptor.
We have constructed a replication-competent gammaretrovirus (SL3-AP) capable of using the human G-protein-coupled receptor hAPJ as its entry receptor. The envelope protein of the virus was made by insertion of the 13-amino-acid peptide ligand for hAPJ, flanked by linker sequences, into one of the variable loops of the receptor binding domain of SL3-2, a murine leukemia virus (MLV) that uses the xenotropic-polytropic virus receptor Xpr1 and which has a host range limited to murine cells. This envelope protein can utilize hAPJ as well as murine Xpr1 for entry into host cells with equal efficiencies. In addition, the SL3-AP virus replicates in cells expressing either of its receptors, hAPJ and murine Xpr1, and causes resistance to superinfection and downregulation of hAPJ in infected cells. Thus, SL3-AP is the first example of a retargeted replication-competent retrovirus, with replication characteristics and receptor interference properties similar to those of natural isolates.


Mechanistic investigations of PEG-directed assembly of one-dimensional ZnO nanostructures.
Mechanistic investigation on spherical assembly of the unique one-dimensional ZnO nanorods, solid nanocones, or hollow prisms with the closed -c end, directed by poly ethylene glycol (PEG) with different molecular weights, has been carried out using spectroscopic methods. The single crystalline ZnO nanoprisms, hollow along the c axis but closed at the -c end, aggregate to urchin-type globules in the microscale when PEG 2000 is used as directing reagent, while spherical aggregates of single crystalline ZnO nanocones are obtained under the direction of PEG 200. Studies reveal that both the PEG molecules aggregate to globules by interacting with zinc species in suitable solvents and englobe the zinc species. By the short time of ultrasonic pretreatment on the solution, a kind of flagellum structure is induced around the globules, in long tubular shapes for PEG 2000 but as shorter wedges for PEG 200. The globules with flagellums are templates for the assembly of the ZnO nanotubes or ZnO nanocones in the hydrothermal treatment. The tiny ZnO crystallites, produced in the hydrothermal process, stack to the templates and amalgamate to single crystalline nanotubes or nanocones, similar to the oriented attachment mechanism. The PEG 2000 template is included in the ZnO cavity of nanotubes, while PEG 200 is excluded from the ZnO nanocones due to the different intertwist properties between the two PEG molecules. Both the urchin-type assemblies, possessing the same external crystalline plane, compose a isotropic powder and emit very strong yellow light, centered at approximately 2.1 eV, under the excitation of the He-Cd laser at 325 nm, which has been correlated to the specific crystal plane. The special powders will be easily coated onto any type of surface for the decoration of a large area of surfaces for future applications.


Nano-selenium alleviates cadmium-induced neurotoxicity in cerebrum via inhibiting gap junction protein connexin 43 phosphorylation.
Cadmium (Cd) as a ubiquitous toxic heavy metal is reported to affect the nervous system. Selenium (Se) has been shown to have antagonistic effects against heavy metal toxicity. In addition, it shows potential antioxidant and anti-inflammatory properties. Thus, the purpose of this study was to determine the possible mechanism of brain injury after high Cd exposure and the mitigation of Nano-selenium (Nano-Se) against Cd-induced brain injury. In this study, the Cd-treated group showed a decrease in the number of neurons in brain tissue, swelling of the endoplasmic reticulum and mitochondria, and the formation of autophagosomes. Nano-Se intervention restored Cd-caused alterations in neuronal morphology, endoplasmic reticulum, and mitochondrial structure, thereby reducing neuronal damage. Furthermore, we found that some differentially expressed genes were involved in cell junction and molecular functions. Subsequently, we selected eleven (11) related differentially expressed genes for verification. The qRT-PCR results revealed the same trend of results as determined by RNA-Seq. Our findings also showed that Nano-Se supplementation alleviated Cx43 phosphorylation induced by Cd exposure. Based on immunofluorescence colocalization it was demonstrated that higher expression of GFAP and lower expressions of Cx43 were restored by Nano-Se supplementation. In conclusion, the data presented in this study establish a direct association between the phosphorylation of Cx43 and the occurrence of autophagy and neuroinflammation. However, it is noteworthy that the introduction of Nano-Se supplementation has been observed to mitigate these alterations. These results elucidate the relieving effect of Nano-Se on Cd exposure-induced brain injury.


Ecological niche modeling predicting the potential distribution of Leishmania vectors in the Mediterranean basin: impact of climate change.
Due to climate change, the geographical distribution of sand flies during the last decades has shifted northward from latitudes below 45°N in southern Europe to latitudes just above 50○N. Recent studies show that some phlebotomine sand flies were recorded in several parts of Germany and Belgium. In central Europe, some autochthone leishmaniasis cases are being recorded in regions traditionally regarded as leishmaniasis-free. An important challenge is to predict the geographical distribution of leishmaniasis vectors under new climatic conditions. In this study, we attempted to predict the current distribution of six leishmaniasis vectors in the Mediterranean basin and forecast species' geographical shift under future climate scenarios using an ensemble ecological niche modeling approach. Species records were obtained from scientific surveys published in the research literature between 2006 and 2016. A series of climate metrics describing temperature and precipitation in the study area under two climatic scenarios were obtained from WorldClim database. A consensus model was derived from six varieties of modeling approaches (regression, machine learning and classification techniques) in order to ensure valid prediction of distribution of vectors under different climate scenarios. Model performance was generally high for the included species with a specificity (true negative rate) ranging from 81.03 to 96.52% (mean = 86.94%) and a sensitivity (true positive rate) ranging from 87.93 to 100% (mean = 96.98%). Our work evidenced the hypothesis of the widespread of Leishmania vectors under climate change scenarios. All of the studied species are prospected to gain new areas that are actually not suitable for vectors' survival. Phlebotomine sand flies are prospected to invade extra-Mediterranean regions, especially western and central Europe. Our study confirmed the importance of environmental and climate factors on the distribution of leishmaniasis vectors and demonstrated the performance of ecological niche modeling in the prediction of the geographical spread of vector-borne diseases. Ecological niche modeling should be considered in the future as a valuable tool in addition to experimental laboratory studies for a better understanding of the biology of vector species.


Whole-Genome Identification and Expression Pattern of the Vicinal Oxygen Chelate Family in Rapeseed (Brassica napus L.).
Vicinal oxygen chelate proteins (VOC) are members of the metalloenzyme superfamily, which plays roles in many biological reactions. Some members of the VOC superfamily have been systematically characterized but not in Brassica napus. In this study, 38 VOC genes were identified based on their conserved domains. The present results revealed that most of the BnaVOC genes have few introns, and all contained the typical VOC structure of βαβββ modules. The BnaVOC genes are distributed unevenly across 15 chromosomes in B. napus and occur as gene clusters on chromosomes C5 and A6. The synteny and phylogenetic analyses revealed that the VOC gene family is a consequence of mesopolyploidy events that occurred in Brassica evolution, and whole-genome duplication and segmental duplication played a major role in the expansion of the BnaVOC gene family. The expression profile analysis indicated that the expression of most BnaVOCs was increased in the leaves and late stage seeds. Further results indicated that seeds of B. napus with a high oil content show higher expression levels under drought stress conditions, suggesting that BnaVOCs not only respond to abiotic stress but may also affect lipid metabolism in drought stress. This present study provides a comprehensive overview of the VOC gene family and provides new insights into their biological function in B. napus evolution.


UGT1A polymorphisms as genetic biomarkers for hepatocellular carcinoma risk in Caucasian population.
The definition of new biomarkers of hepatocellular carcinoma (HCC) risk, especially in high-risk HBV/HCV-positive population, is urgently needed to improve HCC clinical management. This study focused on variants of UDP-glucuronosyltransferase 1A (UGT1A) enzymes that catalyse the reaction of glucuronidation, one of the most important chemical defence pathway of the body. The aim of this study was to elucidate the contribution of UGT1A polymorphisms in predicting HCC susceptibility in Caucasians. In this retrospective case-control analysis, 192 HCC liver transplanted patients represent the study group. Two age/sex-matched groups were used as control, one composed of 167 HBV- and/or HCV-infected individuals, and the other of 192 healthy subjects. All the cases were characterized for a panel of UGT1A1, UGT1A7 and UGT1A9 variants. The study end-point was the association between UGT1A markers and HCC onset. UGT1A7*3 allele emerged as a protective marker for HCC development among both high-risk HBV/HCV-positive patients (OR=0.64, P=.0026), and healthy subjects (OR=0.47, P=.0051). UGT1A1*28 (OR=0.61, P=.0013) and UGT1A9*22 (OR=2.18, P=.0003) alleles were also associated to HCC occurrence, especially among healthy subjects. UGT1A haplotype, summarizing the UGT1A genetic alterations, confirmed the protective role against HCC development emerged for low-activity alleles. The observed associations could probably be linked to an increase of serum levels of health-beneficial molecules including free bilirubin. A predictive effect of UGT1A polymorphisms on HCC risk was identified. If confirmed, these findings could contribute to improve the HCC surveillance, treatment tailoring and patients care.


Health, fortune, and moral authority in medicine.
The Christian conviction about Divine Providence encourages a novel account of the moral content of health and authority in the health care context. While health can be understood as the disposition of a living body to be able to proceed in the world well, as a species of freedom it is informed by the particular projects and concerns that Christians hold deepest. This is due to the fact that health acquires content, and thus becomes desirable as a particular type of good, only in relation to judgments about the good life. Aquinas' reflections concerning the good of health and its partial slavery to fortune reveal a Christian past that dwelt on the intrinsic and instrumental good of health. A rich Christian tradition in which health as intrinsically good, a good of the body, is ordained to the interests of right Christian virtue. Each of these factors affects the character of the health to be pursued and the authority of the physician as determining the ends and means of medicine.


A hypothetical model for the active site of human cytochrome P4502E1.
1. A model for the active site structure of human cytochrome P4502E1 based on the coordinates of cytochrome P450BM-3 crystal structure and the sequence analysis information on P4502E1 was proposed. 2. The sequence alignment of mammalian P4502 family and P450BM-3 indicated a 48%, similarity and 25% identity. Secondary structural prediction displayed a similar pattern of distribution in the main frame of secondary elements, alpha-helices and beta-sheets. The locations of secondary elements also mapped well. In addition, the amino acids responsible for the conserved secondary structural regions showed the most similarity between the two proteins. In contrast, the amino acids responsible for the loop region had the least similarity in our alignment. 3. The predicted P4502E1 active site model shows that the active site is small and contains mainly hydrophobic residues. The substrate binding pocket is located on top of pyrrole rings A and D of the haen; in contrast, the access to B and C rings is partially or completely blocked by protein side chains. 4. Residues within possible contact of a representative substrate, N-nitrosodimethylamine, are He115, Ala299, Thr303, Val364 and possibly He469.


Thermal modeling of the normal woman's breast.
A comprehensive thermal model of the normal woman's breast is presented. The model is developed taking into consideration metabolic heat production, tissue perfusion with capillary blood, arterial and venous blood thermal interaction and change of arterial blood temperature with position. A series of computer programs are written using a 3-dimensional finite-element technique to evaluate the surface temperature distribution of the breast. Comparison between the results obtained for the model and those from thermograms of a woman's breast are in good agreement.


Correspondence regarding Zhong et al., BMC Bioinformatics 2013 Mar 7;14:89.
Computational expression deconvolution aims to estimate the contribution of individual cell populations to expression profiles measured in samples of heterogeneous composition. Zhong et al. recently proposed Digital Sorting Algorithm (BMC Bioinformatics 2013 Mar 7;14:89) and showed that they could accurately estimate population-specific expression levels and expression differences between two populations. They compared DSA with Population-Specific Expression Analysis (PSEA), a previous deconvolution method that we developed to detect expression changes occurring within the same population between two conditions (e.g. disease versus non-disease). However, Zhong et al. compared PSEA-derived specific expression levels across different cell populations. Specific expression levels obtained with PSEA cannot be directly compared across different populations as they are on a relative scale. They are accurate as we demonstrate by deconvolving the same dataset used by Zhong et al. and, importantly, allow for comparison of population-specific expression across conditions.


Safer and more appropriate opioid prescribing: a large healthcare system's comprehensive approach.
The United States is in the midst of a public health epidemic with more than 40 people dying each day from prescription opioid overdoses. Health care systems are taking steps to address the opioid overdose epidemic by implementing policy and practice interventions to mitigate the risks of long-term opioid therapy. Kaiser Permanente Southern California launched a comprehensive initiative to transform the way that chronic pain is viewed and treated. Kaiser Permanente Southern California created prescribing and dispensing policies, monitoring and follow-up processes, and clinical coordination through electronic health record integration. The purpose of this paper is to describe the implementation of these interventions and assess the impact of this set of interventions on opioid prescribing. The study used a retrospective pre-post evaluation design to track outcomes before and after the intervention. Kaiser Permanente Southern California members age 18 and older excluding cancer, hospice, and palliative care patients and this sub-population of 3 203 880 was approximately 75% of all Kaiser Permanente Southern California members. All data are from Kaiser Permanente's pharmacy data systems and electronic health record collected on a rolling basis as interventions were implemented from January 2010 to December 2015. There were reductions in all tracked outcomes: a 30% reduction in prescribing opioids at high doses; a 98% reduction in the number of prescriptions with quantities greater than 200 pills; a 90% decrease in the combination of an opioid prescription with benzodiazepines and carisoprodol; a 72% reduction in the prescribing of Long Acting/Extended Release opioids; and a 95% reduction in prescriptions of brand name opioid-acetaminophen products. In addition, methadone prescribing did not increase during this period. This study adds promising results that a comprehensive system-level strategy has the ability to positively affect opioid prescribing. The basic components of the intervention are generalizable and applicable to other health care settings.


[Spermatogenesis recovery following allogeneic transplantation of undifferentiated Sertoli cells in experimental model of bilateral abdominal cryptorchidism].
This study explores the effect of transplantation of undifferentiated Sertoli cells in the testicular tissue of an experimental animal model of bilateral abdominal cryptorchidism. Effectiveness of undifferentiated Sertoli cell transplantation was assessed after 1 and 3 months after injection. Partial restoration of seminiferous tubules was found to occur after transplantation. In a third of them germ cells of all stages of the differentiation were discovered while they were not found in the control group.


Robust stability of switched Cohen-Grossberg Neural networks with mixed time-varying delays.
By combining Cohen-Grossberg neural networks with an arbitrary switching rule, the mathematical model of a class of switched Cohen-Grossberg neural networks with mixed time-varying delays is established. Moreover, robust stability for such switched Cohen-Grossberg neural networks is analyzed based on a Lyapunov approach and linear matrix inequality (LMI) technique. Simple sufficient conditions are given to guarantee the switched Cohen-Grossberg neural networks to be globally asymptotically stable for all admissible parametric uncertainties. The proposed LMI-based results are computationally efficient as they can be solved numerically using standard commercial software. An example is given to illustrate the usefulness of the results.


Effect of caloric restriction on pre-malignant and malignant stages of mammary carcinogenesis.
Caloric restriction has documented beneficial effects on numerous diseases including cancer, yet the mechanism(s) that accounts for these wide ranging benefits is unknown. Part of the difficulty in defining mechanisms has been the long-term nature of experimental protocols in which these beneficial effects have been observed and the inherent difficulty of investigating mechanisms in such studies. The experiments reported were designed: (1) to determine if caloric restriction would inhibit mammary carcinogenesis in a model for this disease process that is 35 days in duration; (2) to determine if progression from pre-malignant to malignant stages of mammary carcinogenesis was affected by caloric restriction; and (3) to explore whether the effects of caloric restriction were associated with changes in adrenal function. Mammary carcinogenesis was induced in female Sprague-Dawley rats by the i.p. administration of 1-methyl-1-nitrosourea (50 mg/kg body weight) at 21 days of age. Rats were randomized to one of four dietary treatment groups: ad libitum fed, or restriction of food intake to 90, 80 or 60% of the ad libitum intake. Rats were palpated for detection of mammary tumors and all mammary lesions excised at necropsy were histologically classified. Twenty-four-hour collections of urine were obtained at weekly intervals throughout the 35-day experiment. Urine was assayed for corticosterone by direct radioimmunoassay. Caloric restriction resulted in both a dose dependent prolongation of latency to palpable carcinomas (P < 0.01) and a reduction in final incidence of mammary cancer; the dose response was linear (P < 0.05). The percentage of pre-malignant mammary lesions in a group increased with increasing degree of caloric restriction, whereas the percentage of carcinomas decreased (P < 0.05). The level of cortical steroid increased linearly with increasing caloric restriction (P < 0.01) an effect that was not attenuated over time. Poisson regression analyses with the number of cancers per rat as the dependent variable, level of caloric restriction as the independent variable and urinary cortical steroid excretion as a co-variate were performed. These analyses indicated that the variation in cancers per rat, irrespective of the treatment group to which an animal was assigned, could be accounted for by urinary cortical steroid excretion (P<0.05); i.e. urinary cortical steroid excretion was an independent predictor of an animal's carcinogenic response. The data reported in this study support the use of a short term model to study the mechanism(s) by which caloric restriction inhibits mammary carcinogenesis and point to both a stage in the disease process, the conversion of pre-malignant to malignant cells, and a target tissue (adrenal gland) and chemical species (adrenal cortical steroid) that may be involved in mediating the protective effects of energy restriction. These data indicate the feasibility of identifying a chemical basis for the protective effect of caloric restriction that is independent of energy restriction per se and this, in turn, indicates that it may be possible to circumvent the practical problem of implementing a program of chronic energy restriction in human populations, yet still achieve the wide-ranging health benefits of such a program.


Control of IL-6 expression and response in fibroblasts from patients with systemic sclerosis.
Systemic sclerosis (SSc) is an autoimmune connective tissue disease of unknown etiology in which aberrant fibroblast function results in fibrosis of the skin and internal organs. A distinguishing feature of dermal fibroblasts cultured from SSc lesions is that they produce constitutively, i.e., without exogenous stimulation, as much as 30-fold more interleukin-6 (IL-6) than do normal fibroblasts. The present study indicates that the mechanism of constitutive IL-6 secretion involves the accumulation of IL-6 mRNA in affected SSc fibroblasts, mediated by the constitutive binding of nuclear factors to the IL-6 promoter. DNA-protein complexes formed using nuclear extracts of constitutively expressing cells are distinct from those using extracts of normal cells, with or without exogenous stimulation of IL-6; thus, the mechanisms which regulate constitutive and inducible IL-6 gene expression are apparently distinct. The data also demonstrate that dermal fibroblasts respond very rapidly to IL-6 by increasing expression of the IL-6 gene, thus suggesting a mechanism for the establishment and/or persistence of constitutive expression. The constitutive secretion of IL-6 may play an important role in the perpetuation of the local immune dysregulation and fibroblast activation in the SSc lesion.


Network component analysis reveals developmental trajectories of structural connectivity and specific alterations in autism spectrum disorder.
The structural organization of the brain can be characterized as a hierarchical ensemble of segregated modules linked by densely interconnected hub regions that facilitate distributed functional interactions. Disturbances to this network may be an important marker of abnormal development. Recently, several neurodevelopmental disorders, including autism spectrum disorder (ASD), have been framed as disorders of connectivity but the full nature and timing of these disturbances remain unclear. In this study, we use non-negative matrix factorization, a data-driven, multivariate approach, to model the structural network architecture of the brain as a set of superposed subnetworks, or network components. In an openly available dataset of 196 subjects scanned between 5 and 85 years we identify a set of robust and reliable subnetworks that develop in tandem with age and reflect both anatomically local and long-range, network hub connections. In a second experiment, we compare network components in a cohort of 51 high-functioning ASD adolescents to a group of age-matched controls. We identify a specific subnetwork representing an increase in local connection strength in the cingulate cortex in ASD (t = 3.44, P < 0.001). This work highlights possible long-term implications of alterations to the developmental trajectories of specific cortical subnetworks. Hum Brain Mapp 38:4169-4184, 2017. © 2017 Wiley Periodicals, Inc.


Plasticity in the developing auditory cortex: evidence from children with sensorineural hearing loss and auditory neuropathy spectrum disorder.
The developing auditory cortex is highly plastic. As such, the cortex is both primed to mature normally and at risk for reorganizing abnormally, depending upon numerous factors that determine central maturation. From a clinical perspective, at least two major components of development can be manipulated: (1) input to the cortex and (2) the timing of cortical input. Children with sensorineural hearing loss (SNHL) and auditory neuropathy spectrum disorder (ANSD) have provided a model of early deprivation of sensory input to the cortex and demonstrated the resulting plasticity and development that can occur upon introduction of stimulation. In this article, we review several fundamental principles of cortical development and plasticity and discuss the clinical applications in children with SNHL and ANSD who receive intervention with hearing aids and/or cochlear implants.


A novel mutation in major intrinsic protein of the lens gene (MIP) underlies autosomal dominant cataract in a Chinese family.
To identify the causitive mutation in a five-generation family with autosomal dominant congenital total cataract. Clinical and ophthalmological examinations were performed on the affected and unaffected family members. All the members were genotyped with microsatellite markers at loci that were considered to be associated with cataracts. Linkage analysis was performed after genotyping. A mutation was detected by direct sequencing using gene specific primers. Affected individuals in this family showed total cataract. The disease gene was mapping between to a 15.5 Mb interval bounded by D12S368 and D12S1676. A positive two-point LOD score (3.21 at recombination fraction 0) was obtained for the marker D12S90, flanked by D12S368 and D12S1052, on chromosome 12q13.1-21.1. This chromosome encompasses the Major Intrinsic Protein (MIP, MIP26) of the lens, also called aquaporin 0 (AQP0). Sequencing the coding regions of MIP revealed a C>T transition at nucleotide 97 in exon 1 that caused a substitution of arginine (R) to cysteine (C) at codon 33 (p.R33C). This mutation cosegregated with all affected individuals and was not observed in unaffected or in 100 normal unrelated individuals. This study has identified the first dominant cataract mutation in MIP that is located outside the phylogenetically conserved transmembrane domain.


The auto-antigen repertoire in myasthenia gravis.
Myasthenia Gravis (MG) is an antibody-mediated autoimmune disorder affecting the postsynaptic membrane of the neuromuscular junction (NMJ). MG is characterized by an impaired signal transmission between the motor neuron and the skeletal muscle cell, caused by auto-antibodies directed against NMJ proteins. The auto-antibodies target the nicotinic acetylcholine receptor (nAChR) in about 90% of MG patients. In approximately 5% of MG patients, the muscle specific kinase (MuSK) is the auto-antigen. In the remaining 5% of MG patients, however, antibodies against the nAChR or MuSK are not detectable (idiopathic MG, iMG). Although only the anti-nAChR and anti-MuSK auto-antibodies have been demonstrated to be pathogenic, several other antibodies recognizing self-antigens can also be found in MG patients. Various auto-antibodies associated with thymic abnormalities have been reported, as well as many non-MG-specific auto-antibodies. However, their contribution to the cause, pathology and severity of the disease is still poorly understood. Here, we comprehensively review the reported auto-antibodies in MG patients and discuss their role in the pathology of this autoimmune disease.


Lack of effect of Tai Chi Chuan in preventing falls in elderly people living at home: a randomized clinical trial.
To evaluate the effectiveness of Tai Chi Chuan in fall prevention in elderly people living at home with a high risk of falling. Randomized controlled trial. Two industrial towns in the western part of the Netherlands. Two hundred sixty-nine elderly people (average age 77) living at home with a high risk of falling. The intervention group received Tai Chi Chuan training for 1 hour twice a week for 13 weeks; the control group received usual care. Both groups received a brochure containing general information on how to prevent fall incidents. Primary outcome was the number of falls over 12 months. Secondary outcomes were balance, fear of falling, blood pressure, heart rate at rest, forced expiratory volume during the first second, peak expiratory flow, physical activity, and functional status. After 12 months, no lower fall risk in the Tai Chi Chuan group was observed than in the control group (adjusted hazard ratio=1.16; 95% confidence interval=0.84-1.60), and there were no significant intervention effects on the secondary outcome measures. These results suggest that Tai Chi Chuan may not be effective in elderly people at a high risk of falling who live at home.


Capacitance effect on the oscillation and switching characteristics of spin torque oscillators.
We have studied the capacitance effect on the oscillation characteristics and the switching characteristics of the spin torque oscillators (STOs). We found that when the external field is applied, the STO oscillation frequency exhibits various dependences on the capacitance for injected current ranging from 8 to 20 mA. The switching characteristic is featured with the emerging of the canted region; the canted region increases with the capacitance. When the external field is absent, the STO free-layer switching time exhibits different dependences on the capacitance for different injected current. These results help to establish the foundation for capacitance-involved STO modeling.


Comparison of Therapeutic Effectiveness Between Shoulder Distention Arthrography With Translation Mobilization and Distention Arthrography Alone in Patients With Frozen Shoulder.
To evaluate the efficacy of distention arthrography (DA) alone and in combination with translational mobilization (TM) for treatment of patients with frozen shoulder (FS). Eighty-five patients diagnosed with unilateral FS (freezing or frozen stage) were included. Forty-one patients were treated with DA and TM (group 1) and 44 patients with DA alone (group 2). Clinical assessments including visual analogue scale (VAS), Cyriax stage, and shoulder passive range of motion (PROM) including forward flexion, abduction, external rotation, and internal rotation were measured at baseline, 1 month, and 3 months following treatment. There were no significant differences in gender, side affected, symptom duration, presence of diabetes mellitus, VAS score, Cyriax stage, or shoulder PROM between the two patient groups at baseline. Compared with baseline metrics, patients in both groups demonstrated significantly improved outcome parameters at two post-treatment time points. However, mean all shoulder PROMs were significantly greater, and mean VAS score and Cyriax stage were lower in patients treated with DA and TM than in those treated with DA alone group at two post-treatment time points. At these times, mean interval change of all outcome parameters was significantly greater with DA and TM than DA alone. No serious complications were observed following treatment in either patient group. Compared with DA alone, DA combined with TM more effectively alleviates shoulder pain and increases PROM in patients with freezing or frozen stage FS.


Network analysis of DEGs and verification experiments reveal the notable roles of PTTG1 and MMP9 in lung cancer.
Lung cancer, a malignant tumor, is the most frequently fatal cancer, with poor survival rates in the advanced stages. In order to improve the understanding of this disease, and to improve the outcomes of patients, additional studies are required. In the present study, differentially expressed genes (DEGs) in patients with lung cancer compared with controls were identified. To understand how these DEGs act together to account for the initiation of lung cancer, a protein interaction network and a transcriptional regulatory network were constructed to explore the clusters and pathways in lung cancer, and the results indicated that PTTG1 and MMP9 served major roles in the development of lung cancer in the regulatory system. Consistent with this, mRNA and protein expression levels of PTTG1 and MMP9 were significantly upregulated in lung cancer tissues compared with normal lung tissues. The overexpression of PTTG1 or MMP9 was induced in the human bronchial epithelial BEAS-2B cell line, indicating that increased PTTG1 or MMP9 alone may not only facilitate cell migration, proliferation and induce colony formation, but also suppress cell apoptosis. In summary, PTTG1 and MMP9 were identified as potential targets for therapeutic intervention through gene therapy in lung cancer.


Systemic venous oxygen saturation after the Norwood procedure and childhood neurodevelopmental outcome.
Neonates with hypoplastic left heart syndrome have impaired systemic oxygen delivery and also have a high risk of hypoxic ischemic brain injury with resultant neurodevelopmental impairment. We hypothesized that decreased postoperative oxygen delivery, as measured on the basis of systemic venous oxyhemoglobin saturation, would be related to persistent neurodevelopmental abnormality assessed in childhood. Early perioperative hemodynamic data, prospectively acquired from neonates undergoing staged palliation of hypoplastic left heart syndrome by using deep hypothermic circulatory arrest with uniform perioperative management, were tested for relationship to later neurodevelopmental outcome assessed at age 4 years. Complete hemodynamic and neurodevelopmental data were available in 13 patients aged 7 +/- 8 days at the time of the Norwood procedure and aged 4.5 +/- 0.7 years at follow-up assessment. The subjects scored significantly below the population mean for motor, visual-motor integration, and composite neurodevelopmental outcomes. The 5 (38%) patients with abnormal outcomes had significantly lower postoperative systemic venous oxygen saturation values than those with normal outcomes (46% +/- 8% vs 56% +/- 6%, P = .024). Standard hemodynamic parameters did not differentiate patient outcomes. The risk of abnormal outcome increased with increasing time at a systemic venous oxygen saturation of less than 40% (P < .001). A multivariate model of deep hypothermic circulatory arrest time, systemic venous oxygen saturation, blood pressure, and carbon dioxide tension accounted for 79% of the observed variance (P < .001). Decreased systemic oxygen delivery in the neonatal postoperative period is associated with hypoxic-ischemic brain injury and childhood neurodevelopmental abnormality. Measures of systemic oxygen delivery should be used to guide perioperative strategies to reduce the risk of hypoxic-ischemic brain injury.


Characterization of food physical properties by the mastication parameters measured by electromyography of the jaw-closing muscles and mandibular kinematics in young adults.
The relationship between the physical properties of solid food and the masticatory parameters is clarified. Eight solid foods of varying physical properties were chosen. Electromyography of the jaw-closing muscles and mandibular kinematics in eleven young subjects were recorded. The masticatory parameters were derived from the recorded data for the entire mastication process, for the first bite, and in the early, middle, and late stages of mastication. After calculating values relative to the mean value for each subject, nine parameters representing each group were chosen through a cluster analysis. Three principal components were extracted, each of them related to the masticatory time and cycle, minimum jaw opening at the early stage of mastication, and masticatory force. The principal component scores for each food were different, except for one combination in which the physical properties under large and extra-large deformations were similar, despite different breaking properties or small deformation properties. The masticatory parameters did not correlate with the physical properties of food measured for small deformation.


Use of viral infections in animal models to assess changes in the immune system.
Viral infections in animal models appear to be ideal systems for determining toxicity to the immune system by environmental substances. Since many viral infections that are utilized in animals produce systemic disease, these models provide an opportunity to evaluate the interaction between virus and components of host resistance. In these infections it is possible to delineate the role of antibody, interferon, cell-mediated immunity, neutrophils and macrophages in response to infection. A change in any of these components responsible for resistance to a particular virus may be correlated with an alteration of mortality an pathogenesis of the viral infection. Three experimental viral infections in mice that are potential candidates for use in determining immunotoxicity are discussed in terms of the response of individual components of resistance to infection and how changes in there components result in alterations of viral pathogenesis. The resistance to encephalomyocarditis virus infection in mice appears to be primarily mediated by antibody and interferon while with herpes simplex virus, infections are mainly controlled through cell-mediated immunity, macrophages, and possible interferon. Cellular immunity also appears to be primarily responsible for resistance to cytomegalovirus infections. Therefore, it is important in the use of these systems for evaluating immunotoxicity to define the pathogenesis of the viral infection and the specific host responses to these infections and to be able to correlate a change in host resistance with an alteration of the viral infection.


Highly productive CNN pincer ruthenium catalysts for the asymmetric reduction of alkyl aryl ketones.
Chiral pincer ruthenium complexes of formula [RuCl(CNN)(Josiphos)] (2-7; Josiphos = 1-[1-(dicyclohexylphosphano)ethyl]-2-(diarylphosphano)ferrocene) have been prepared by treating [RuCl(2)(PPh(3))(3)] with (S,R)-Josiphos diphosphanes and 1-substituted-1-(6-arylpyridin-2-yl)methanamines (HCNN; substituent = H (1 a), Me (1 b), and tBu (1 c)) with NEt(3). By using 1 b and 1 c as a racemic mixture, complexes 4-7 were obtained through a diastereoselective synthesis promoted by acetic acid. These pincer complexes, which display correctly matched chiral PP and CNN ligands, are remarkably active catalysts for the asymmetric reduction of alkyl aryl ketones in basic alcohol media by both transfer hydrogenation (TH) and hydrogenation (HY), achieving enantioselectivities of up to 99 %. In 2-propanol, the enantioselective TH of ketones was accomplished by using a catalyst loading as low as 0.002 mol % and afforded a turnover frequency (TOF) of 10(5)-10(6) h(-1) (60 and 82 degrees C). In methanol/ethanol mixtures, the CNN pincer complexes catalyzed the asymmetric HY of ketones with H(2) (5 atm) at 0.01 mol % relative to the complex with a TOF of approximately 10(4) h(-1) at 40 degrees C.


Aging of natural and acquired immunity of mice. I. Decreased natural killer cell function and hybrid resistance.
Two "natural resistance" functions, natural killer (NK) cell activity against YAC-1 lymphoma cells and rejection by irradiated mice of parental-strain or H-2 allogeneic bone marrow cell grafts (hybrid or allogeneic resistance) were compared in mice at ages between 10 weeks and 26 months. NK cell numbers, as assessed by target-binding cells, decreased to one-half that of young mouse spleen cells, whereas NK lytic function was much more depressed. Hybrid, but not allogeneic, resistance to marrow grafts was weakened by 17 months of age. The immunogenicity of marrow stem cells of old Fl hybrid mice had not changed. The interferon inducer polyinosinic:polycytidylic acid (pI:pC) restored hybrid resistance to marrow grafts but only weakly boosted NK cell function in old mice. Incubation of spleen cells of old mice with beta interferon resulted in a weak boosting of NK cell activity. No cells capable of inhibiting NK cell function were detected in the spleens of old mice. These findings in old mice were similar to findings in young mice treated with 89Sr, with the exceptions that both hybrid and allogeneic resistance to marrow grafts are defective in 89Sr-treated mice and pI:pC failed to restore hybrid resistance in mice treated with 89Sr. This loss of "natural resistance" by aged mice, perhaps mediated by marrow-dependent effector cells, can partially explain the increased incidence of tumors in aging populations.


Scalable, Stereocontrolled Formal Syntheses of (+)-Isoschizandrin and (+)-Steganone: Development and Applications of Palladium(II)-Catalyzed Atroposelective C-H Alkynylation.
Dibenzocyclooctadiene lignans are an interesting class of molecules because of their unique structure based on an axially chiral biaryl moiety as well as their significant biological activity. Herein, we describe the development of a palladium-catalyzed atroposelective C-H alkynylation and its application in gram-scale, stereocontrolled formal syntheses of (+)-isoschizandrin and (+)-steganone. tert-Leucine was identified as an efficient, catalytic transient chiral auxiliary. A wide range of enantiomerically enriched biaryl compounds were prepared by this approach in good yields (up to 99 %) with excellent enantioselectivity (up to >99 % ee).


Femoral metastases from carcinoma of the breast. Pathological and clinical aspects.
In long bone metastases from breast carcinoma, the femur is the bone most frequently involved. Osteolysis is brought about by the osteoclasts, by the neoplastic cells themselves, and to some extent by autolysis of the osseous tissue adjacent to the metastasis. When the metastases are asymptomatic, radiotherapy and antiblastic chemotherapy are indicated, but with symptomatic metastases and spontaneous fractures surgical intervention is indicated. This consists either of prosthetic replacement or of intramedullary fixation complemented by chemotherapy and radiotherapy.


Rare primary CNS anaplastic large cell lymphoma in an immunocompetent adult: a clinical-pathologic case report and review case of the literature.
Isolated anaplastic large cell lymphoma (ALCL) presenting in the primary central nervous system is distinctly uncommon. The authors describe a case that clinically and radiographically simulated a primary glial neoplasm. A 39-year-old immunocompetent male presented with seizures and a rapidly enlarging right occipital/parietal lesion. Magnetic resonance images demonstrated a right occipitoparietal lesion, hypodense on T1WI, with patchy contrast enhancement with gadolinium and significant white matter edema pattern on T2WI along with mass effect and midline shift. The patient underwent a frameless stereotactic assisted needle biopsy. There appeared to be a clear demarcation between white matter and tumor with no obvious necrosis. Biopsy showed a proliferation of single cells and poorly cohesive groups of cells with large, pleomorphic nuclei, many containing prominent nucleoli, and a moderate amount of cytoplasm. Immunohistochemical staining revealed CD-30 and ALK-positivity typical of ALCL, a rare form of T-cell lymphoma. An extensive workup revealed neither systemic disease nor evidence of immunocompromise. Reported in less than 20 patients, primary ALCL in an immunocompetent patient is rarely found intracranially; however, its ability to mimic glial neoplasms as well as other pathologies underlines its importance.


Dietary obesity shows adaptations of amino-acid metabolism on enzyme activities to save amino nitrogen.
An increased aspartate transaminase in the liver of dietary (post-cafeteria) obese rats was found. It was consistent with the functionality of the malate-aspartate shuttle, that could be responsible for enhancement of metabolic efficiency. The muscle and intestine of obese rats showed a greater capacity for alanine and glutamine synthesis than the controls. Furthermore, enterocyte adaptations in the obese rats indicated higher capabilities for the intake of nitrogen than in the controls. In conclusion, the pattern of amino-acid enzyme activities reflected adaptations to keep from amino nitrogen depletion in dietary obesity which were compatible with an enhancement of the metabolic efficiency.


The seven-step, one-pot regioselective synthesis of biologically important 3-aryllawsones: scope and applications.
3-Aryllawsones are well known for their wide range of applications in medicinal chemistry, but their synthesis has always remained challenging as no comprehensive protocol has been outlined to date. Owing to their structural importance, we synthesized various 3-aryllawsones with high regioselectivity from simple lawsone and aldehydes in a seven-step double-cascade one-pot reaction through the combination of organocatalytic Ramachary reductive coupling and Hooker oxidation reactions. The commercial availability of the starting materials, diverse substrate scope, possibility of a one- or two-pot approach, regioselectivity of alkyl transfer (with mechanistic proof provided via X-ray crystal structure analysis), and numerous medicinal applications of 3-aryllawsones are the key attractions of this work.


Frustration across the periodic table: heterolytic cleavage of dihydrogen by metal complexes.
This perspective examines frustrated Lewis pairs (FLPs) in the context of heterolytic cleavage of H2 by transition metal complexes, with an emphasis on molecular complexes bearing an intramolecular Lewis base. FLPs have traditionally been associated with main group compounds, yet many reactions of transition metal complexes support a broader classification of FLPs that includes certain types of transition metal complexes with reactivity resembling main group-based FLPs. This article surveys transition metal complexes that heterolytically cleave H2, which vary in the degree that the Lewis pairs within these systems interact. Many of the examples include complexes bearing a pendant amine functioning as the base with the metal functioning as the hydride acceptor. Consideration of transition metal compounds in the context of FLPs can inspire new innovations and improvements in transition metal catalysis.This article is part of the themed issue 'Frustrated Lewis pair chemistry'.


[Self-esteem and its relations with self-image in female adolescents suffering from anorexia nervosa].
The paper presents results of research concerning the differences in self-esteem and their relations with self-image in female adolescents with anorexia nervosa (who meet criteria of DSM-IV) and their healthy peers. Every group consisted of 30 individuals. They completed the Culture-Free Self-Esteem Inventory, which enables measuring the self-esteem in three aspects: general self-esteem, personal self-esteem and social self-esteem. The study revealed lower self-esteem in girls suffering from anorexia nervosa than in the control group. Lower self-esteem of anorectic girls is connected with their emotions toward themselves and their social relations.


Phytonutrient supplements and metabolic biomarkers of cardiovascular disease: An umbrella review of meta-analyses of clinical trials.
Phytonutrients exert several pharmacological effects on humans. In this study, we performed an umbrella review of the association of phytonutrient supplements (PNSs) with biomarkers of cardiovascular disease. Relevant published systematic reviews and meta-analyses of clinical trials were identified by searching PubMed, Embase, and Cochrane Library until July 4, 2020. Weighted mean differences (WMDs) and 95% confidence intervals (CIs) for summarized effects and I2 statistics of heterogeneity were extracted from individual studies or reanalyzed using a random-effects model. Of the 50 included studies, pooled effects of PNSs on blood pressure, lipid profiles, and glycemic control were reported in 16, 25, and 14 articles, respectively. The findings appeared to be highly heterogeneous among individual trials of included systematic reviews and meta-analyses. Ginger (WMD = -6.36 mmHg, 95% CI = -11.27, -1.46) and Hibiscus sabdariffa (WMD = -7.58 mmHg, 95% CI = -9.69, -5.46) were associated with lowered systolic blood pressure, whereas Aloe vera, Nigella sativa, and spirulina were associated with beneficial effects on both lipid profiles and glycemic control. In summary, this umbrella review has provided up-to-date evidence for the effect of PNSs on biomarkers related to hypertension, dyslipidemia, and diabetes. The results must be interpreted with caution due to potential heterogeneity.


Making estimates and sensitivity to anchors: exploring the role of hemispheric processing.
In this paper we set out to explore how the processing differences associated with the respective hemispheres would influence susceptibility to anchoring effects. To do so we provided participants with both a positive and negatively valenced anchoring task. Based on prior research, we predicted stronger anchoring effects under conditions of right hemisphere activation and relatively attenuated anchoring effects under left hemisphere activation. Further, based on the valence hypothesis, we predicted stronger anchoring effects under conditions of hemispheric-valence consistency. Our results support the former hypothesis but do not support the latter.


State-matched organoid models to fight pancreatic cancer.
As one of the deadliest cancers, pancreatic ductal adenocarcinoma (PDAC) requires sophisticated model systems to dissect disease onset, progression, and therapy resistance, as well as to personalize therapy. In recent years, patient- and pluripotent stem cell-derived organoids have become state-of-the-art systems to refine existing therapeutic strategies and deepen our knowledge of disease pathophysiology.


Complete mitochondrial genome of the Sinibrama macrops (Cyprinidae: Cultrinae).
The complete mitochondrial genome of Sinibrama macrops was first determined in this study. The genome is 16,626 bp in length, including 13 protein-coding genes, 2 ribosomal RNA genes, 22 transfer RNA genes and 1 control region. Its gene arrangement and translation direction were identical to those of other typical vertebrates. The overall base composition is 30.7% A, 27.9% C, 16.7% G and 24.7% T, with the negative GC skew value ( - 0.251). In a long term, S. macrops was confused with Sinibrama wui, which was confirmed as an invalid species by recent morphological study. Therefore, the mitochondrial genome of S. macrops can contribute to the molecular identification of the species and further phylogenetic study of Cyprinidae.


Mechanoregulation of monocyte chemoattractant protein-1 expression in rat vascular smooth muscle cells.
The authors have previously shown that arterial wall strain mediates the development of vessel wall inflammation in experimental hypertension. The current studies explore the mechanoregulation of monocyte chemoattractant protein-1 (MCP-1), a potent pro-inflammatory chemokine, by mitogen-activated protein kinases (MAPK) and oxidative stress. Rat aortic smooth muscle (RASM) cells were subjected to cyclic strain on a uniform biaxial strain device. Strain rapidly activated both ERK1/2(MAPK) and p38(MAPK), with peak activation at 5 min. Strain induced a twofold increase in MCP-1 mRNA, which was attenuated by PD 98059, a specific ERK1/2(MAPK) inhibitor, and SB 203580, a specific p38(MAPK) inhibitor. Cyclic strain also increased production of superoxide anion via an NADPH oxidase-dependent mechanism. To assess the potential role of reactive oxygen species in MAPK activation, cells were stretched in the presence of N-acetylcysteine, which had no effect on p38(MAPK) activation, but significantly inhibited ERK1/2(MAPK) activation and MCP-1 expression. In conclusion, redox-sensitive activation of ERK1/2(MAPK) and redox-insensitive activation of p38(MAPK) regulate straininduced MCP-1 expression in RASM cells. These findings define a role for MAPK signal transduction in establishing a pro-inflammatory state in the arterial wall, and thus implicate a potential molecular link between arterial wall strain and atherosclerosis.


Carotid angioplasty.
Aspirin and carotid endarterectomy represent the current method of prophylaxis against stroke in patients with symptomatic high grade carotid stenoses. Whilst balloon dilatation and stent placement is an accepted form of recannalization, elsewhere in the arterial circulation the technique is in its infancy within the supra-aortic vessels. Carotid endarterectomy is expensive, requires a general anaesthetic and is associated with an acceptable complication rate as demonstrated by the ECST and NASCET studies. The author's experience in 55 patients with symptomatic high grade atherosclerotic disease is described with a disabling stroke rate at 30 days similar to the surgical series (5%). Long-term follow-up is awaited. Metallic intra-arterial stents provide the opportunity to reduce the immediate postintervention residual stenosis and possibly reduce the long-term restenosis rate. Modifications of the technique are in development and may reduce the cerebral embolization that occurs during the procedure.


Longitudinal profiling of the lung microbiome in the AERIS study demonstrates repeatability of bacterial and eosinophilic COPD exacerbations.
Alterations in the composition of the lung microbiome associated with adverse clinical outcomes, known as dysbiosis, have been implicated with disease severity and exacerbations in COPD. To characterise longitudinal changes in the lung microbiome in the AERIS study (Acute Exacerbation and Respiratory InfectionS in COPD) and their relationship with associated COPD outcomes. We surveyed 584 sputum samples from 101 patients with COPD to analyse the lung microbiome at both stable and exacerbation time points over 1 year using high-throughput sequencing of the 16S ribosomal RNA gene. We incorporated additional lung microbiology, blood markers and in-depth clinical assessments to classify COPD phenotypes. The stability of the lung microbiome over time was more likely to be decreased in exacerbations and within individuals with higher exacerbation frequencies. Analysis of exacerbation phenotypes using a Markov chain model revealed that bacterial and eosinophilic exacerbations were more likely to be repeated in subsequent exacerbations within a subject, whereas viral exacerbations were not more likely to be repeated. We also confirmed the association of bacterial genera, including Haemophilus and Moraxella, with disease severity, exacerbation events and bronchiectasis. Subtypes of COPD have distinct bacterial compositions and stabilities over time. Some exacerbation subtypes have non-random probabilities of repeating those subtypes in the future. This study provides insights pertaining to the identification of bacterial targets in the lung and biomarkers to classify COPD subtypes and to determine appropriate treatments for the patient. Results, NCT01360398.


An Evaluation of a Factor Xa-Based Clotting Time Test for Enoxaparin: A Proof-of-Concept Study.
A well-accepted test for monitoring anticoagulation by enoxaparin is not currently available. As inadequate dosing may result in thrombosis or bleeding, a clinical need exists for a suitable test. Previous in silico and in vitro studies have identified factor Xa as an appropriate activating agent, and the phospholipid Actin FS as a cofactor for a Xa clotting time (TenaCT) test. A proof-of-concept study was designed to (1) explore the reproducibility of the TenaCT test and (2) explore factors that could affect the performance of the test. In vitro clotting time tests were carried out using plasma from 20 healthy volunteers. The effect of enoxaparin was determined at concentrations of 0.25, 0.50, and 1.0 IU/mL. Clotting times for the volunteers were significantly prolonged with increasing enoxaparin concentrations. Clotting times were significantly shortened for frozen plasma samples. No significant differences in prolongation of clotting times were observed between male and female volunteers or between the 2 evaluated age groups. The clotting times were consistent between 2 separate occasions. The TenaCT test was able to distinguish between the subtherapeutic and therapeutic concentrations of enoxaparin. Plasma should not be frozen prior to performing the test, without defining a frozen plasma reference range. This study provided proof-of-concept for a Xa-based test that can detect enoxaparin dose effects, but additional studies are needed to further develop the test.


[Outbreak of multi-resistant Escherichia coli on a surgical ward: course, measures and consequences for future admissions of contaminated patients].
In the period July-September 2003, a multi-resistant Escherichia coli strain caused an outbreak on a surgical ward in the Deventer Hospital, the Netherlands. This strain produced a beta-lactamase with an extended spectrum, making it resistant to third generation cephalosporins. Furthermore, the strain was resistant to trimethoprim-sulphamethoxazole (co-trimoxazole), gentamicin and quinolones, so that only treatment with carbapenems was possible. 8 patients were colonised. Genotyping of the strains by means of amplified fragment length polymorphism indicated the spread of a single strain. A multidisciplinary crisis team coordinated the infection control measures and the communication to involved persons and the press. Control measures consisted of contact isolation of colonised patients and extra attention to hand hygiene. After this proved to be ineffective, all patients on the ward were screened and the ward was closed for several days. The outbreak was stopped by strict cohorting ofthe colonised patients. There were no indications for transmission of resistance genes by plasmids. Several months later, on visiting the outpatient clinic, 3 other patients appeared to have been colonised by the epidemic E. coli strain during their admission. They had not been screened because they had already been discharged when all patients on the ward were screened for colonisation. In a follow-up study 9 months after the outbreak, 3 of the 6 investigated patients, who had in the meantime returned home, were still found to be colonised. Such patients constitute a risk for the re-introduction of multi-resistant bacteria into the hospital and should be preventively screened and isolated on admission.


[Current Situation and Advances in Diagnosing Triple-negative Breast Cancer Using Ultrasound].
Triple-negative breast cancer is a complex type of breast cancer,the most common malignant tumor in women.Since the early image features of triple-negative breast cancer appear benign tumor with rapid growth,this cancer has progressed into the middle and late stages once diagnosed,which leads to high mortality.Therefore,the diagnosis of triple-negative breast cancer has always been a clinical difficulty.This article summarizes the role of ultrasound in the diagnosis and treatment of triple-negative breast cancer.The extracted multi-mode ultrasound features will facilitate the early detection of this cancer and improve the prognosis of these patients.


Genetic evaluation using parentage information from genetic markers.
Genetic evaluation relies on pedigree information to account for the trait information on individuals and their relatives. Recording pedigrees may place unfavorable restrictions on the management of breeding populations, such as the use of single-sire mating groups and the observation of parturition. The use of DNA marker information is an alternative method to identify parents, but it is difficult to assign the parents unambiguously for all progeny in extensively farmed livestock without the use of very many markers. We present methods that use DNA information on parentage within a genetic evaluation system that allow for genotyping errors and for the parentage information to be incomplete, with probabilities assigned to possible parent pairs (i.e., fractional parentage assignment). Two of these methods use a computing strategy that circumvents the high memory requirements associated with the application of previous methods designed for use with fractional parentage assignment. This strategy has an additional advantage of allowing the same statistical models to be used in the evaluation as with recorded pedigrees. The use of DNA marker-based parentage for genetic evaluation is associated with lower genetic gain (at the same survival levels) than by using the true pedigree. This decrease in gain depends on a number of factors, including trait heritability and the DNA markers used. The methods we have described show how DNA marker information could be used to replace traditional pedigree recording.


La-Doped Ultrahigh-Nickel Layered Oxide Cathode with Enhanced Cycle Stability for Li-Ion Batteries.
Currently, ultrahigh-nickel layered oxide is one of the most promising cathodes for lithium-ion batteries, with the advantages of high theoretical capacity and low cost. However, some problems in ultrahigh-nickel layered oxides are more serious, such as irreversible structural transformation, particle cracking, and side reactions at the electrode/electrolyte interface, resulting in the fast decay of the discharge capacity and midpoint potential. In this work, La doping is introduced into ultrahigh-nickel layered LiNi0.9Co0.1O2 oxide to improve the cycle stability on both discharge capacity and midpoint potential. As demonstrated, La can be doped successfully into the subsurface of LiNi0.9Co0.1O2 oxide, and the morphology of the oxide microspheres is not changed obviously by La doping. Compared with the pristine sample, the La-doped sample presents improved electrochemical performance, especially good cycle stabilization on both discharge capacity and midpoint potential. In addition, after a long-term cycle, the La-doped sample still maintains a relatively complete spherical morphology. It means that the pillaring effect of La with a large radius is helpful in accommodating the volume change caused by the insertion/extraction of Li ions, thus easing the anisotropic stress accumulation and microcrack growth inside the microspheres of the La-doped sample.


The diversity of volume regulatory mechanisms.
Mammalian cells utilize a wide variety of cell volume regulatory mechanisms. For rapid adjustment of cell volume cells release or accumulate ions through respective channels and transport systems across the cell membrane. The most widely used mechanisms of cell volume regulatory ion release include ion channels and KCl symport. Ion uptake is most frequently mediated by Na+ channels, Na+, K+, 2Cl- cotransport, and Na+/H+ exchange. Chronic adjustment of cell osmolarity is accomplished by the formation or accumulation of organic osmolytes, molecules specifically designed to create intracellular osmolarity without interfering with cellular function. The most widely occurring osmolytes are sorbitol, inositol, glycerophosphorylcholine, betaine, taurine, and amino acids. The osmolytes are either synthesized by or transported into shrunken cells. During cell swelling osmolytes can be rapidly degraded or released. Any given cell may utilize several volume-regulatory mechanisms. Moreover, different mechanisms are utilized in different tissues. The diversity of cell volume regulatory mechanisms allows the cells to defend the constancy of cell volume against a myriad of challenges with relatively little impairment of cellular function.


Anthocyanins and their variation in red wines. II. Anthocyanin derived pigments and their color evolution.
Originating in the grapes, anthocyanins and their derivatives are the crucial pigments responsible for the red wine color. During wine maturation and aging, the concentration of monomeric anthocyanins declines constantly, while numerous more complex and stable anthocyanin derived pigments are formed, mainly including pyranoanthocyanins, polymeric anthocyanins produced from condensation between anthocyanin and/or flavan-3-ols directly or mediated by aldehydes. Correspondingly, their structural modifications result in a characteristic variation of color, from purple-red color in young red wines to brick-red hue of the aged. Because of the extreme complexity of chemical compounds involved, many investigations have been made using model solutions of know composition rather than wine. Thus, there is a large amount of research still required to obtain an overall perspective of the anthocyanin composition and its change with time in red wines. Future findings may well greatly revise our current interpretation of the color in red wines. This paper summarizes the most recent advances in the studies of the anthocyanins derived pigments in red wines, as well as their color evolution.


Genetic counseling in pediatric acute care: Reflections on ultra-rapid genomic diagnoses in neonates.
As genomic sequencing has become available in pediatric clinical genetics settings, genetic counselors have been called upon to support individuals and families through the testing process. Technological and bioinformatic advancements, along with the availability of analytical expertise, have significantly reduced genomic sequencing turnaround times, enabling this powerful diagnostic tool to be used in neonatal intensive care units (NICUs) in place of or alongside traditional diagnostic strategies. It is important that pretest counseling for genomic sequencing prepares parents of critically unwell infants for the potential impacts of achieving a diagnosis, such as rare or ultra-rare diagnoses with limited disease-specific information, or the diagnosis of a life-limiting condition. Genetic counseling experiences and challenges arising in rapid genomic sequencing settings are yet to be discussed in the literature in detail. This paper uses illustrative cases as the basis to describe and discuss the emerging role of genetic counselors in NICU multidisciplinary care teams and the challenges and considerations which arise when facilitating ultra-rapid genomic diagnoses in acutely unwell neonates. Counseling issues discussed include providing pre- and posttest counseling in the medicalized NICU setting, facilitating informed decision-making at a time of acute distress for families, and special considerations around the possibility of ultra-rare diagnoses in neonates at the beginning of their diagnostic trajectory. As technology continues to drive practice, it is important genetic counselors remain abreast of these issues in order to appropriately support families through the genomic sequencing process and beyond.


Protease-activated receptor 1 is implicated in irritable bowel syndrome mediators-induced signaling to thoracic human sensory neurons.
Proteases and protease-activated receptors (PARs) are major mediators involved in irritable bowel syndrome (IBS). Our objectives were to decipher the expression and functionality (calcium signaling) of PARs in human dorsal root ganglia (DRG) neurons and to define mechanisms involved in human sensory neuron signaling by IBS patient mediators. Human thoracic DRG were obtained from the national disease resource interchange. Expression of PAR1, PAR2, and PAR4 was assessed by immunohistochemistry and quantitative reverse transcription PCR (RT-qPCR) in whole DRG or in primary cultures of isolated neurons. Calcium signaling in response to PAR agonist peptides (PAR-AP), their inactive peptides (PAR-IP), thrombin (10 U/mL), supernatants from colonic biopsies of patients with IBS, or healthy controls, with or without PAR1 or PAR4 antagonist were studied in cultured human DRG neurons. PAR1, PAR2, and PAR4 were all expressed in human DRG, respectively, in 20%, 40%, and 40% of the sensory neurons. PAR1-AP increased intracellular calcium concentration in a dose-dependent manner. This increase was inhibited by PAR1 antagonism. By contrast, PAR2-AP, PAR4-AP, and PAR-IP did not cause calcium mobilization. PAR1-AP-induced calcium flux was significantly reduced by preincubation with PAR4-AP, but not with PAR2-AP. Thrombin increased calcium flux, which was inhibited by a PAR1 antagonist and increased by a PAR4 antagonist. Supernatants from colonic biopsies of patients with IBS induced calcium flux in human sensory neurons compared with healthy controls, and this induction was reversed by a PAR1 antagonist. Taken together, our results highlight that PAR1 antagonism should be investigated as a new therapeutic target for IBS symptoms.


Fibrin formation by wounded bronchial epithelial cell layers in vitro is essential for normal epithelial repair and independent of plasma proteins.
The bronchial epithelium is in contact with, and continually damaged by, the environment. Animal models have indicated that normal epithelial repair is rapid and supported by the formation of a provisional fibrin matrix that is exclusively plasma-derived. Our objectives were to demonstrate the ability of normal human bronchial epithelial (NHBE) cells to produce coagulation cascade proteins and form fibrin in response to damage, independently of plasma proteins, and to show that formation of a cross-linked fibrin matrix is essential for normal epithelial repair in vitro. Primary NHBE cells and cells of the 16HBE 14o- bronchial epithelial cell line were grown and maintained in vitro prior to mechanical wounding of confluent monolayers in serum-free media. Tissue factor (TF) and factor XIII (FXIII) were visualized on 16HBE 14o- monolayers using immunohistochemistry. The time-dependent expression of TF, factor VII (FVII), factor X (FX), fibrinogen, soluble fibrin, FXIII subunit A (FXIIIA) and D-dimers following wounding of confluent 16HBE 14o- monolayers was investigated using immunoassays. TF and FVII expression at the mRNA level was investigated by RT-PCR. The role of coagulation cascade proteins in the repair response of NHBE and 16HBE 14o- monolayers was investigated using neutralizing antibodies. Active TF was constitutively expressed in 16HBE 14o- cells. Levels of FVII, FX, fibrinogen, soluble fibrin, FXIIIA and D-dimers in culture supernatants increased rapidly and were maximal 20 min after wounding the monolayers. Expression of TF and FVII mRNA was significantly increased 10 and 4 h, respectively, after wounding. Neutralizing antibodies to TF, fibrinogen and FXIIIA significantly inhibited repair of NHBE and 16HBE 14o- cell layers. The bronchial epithelium has the potential to respond rapidly to mechanical damage by forming a cross-linked fibrin matrix that is essential for normal epithelial repair, independently of plasma proteins.


Photo- and Thermosensitive Molecular Crystals. Valence Tautomeric Interconversion as the Cause of the Photomechanical Effect in Crystals of Bis(dioxolene)cobalt Complex.
Especially grown crystals (elongated plates) of the complex (1,10-phen)Co(3,6-DBSQ)2 (1) reversibly elastically bend under laser excitation (532 or 808 nm) and/or heating in the temperature interval ∼242-265 K (1,10-phen = 1,10-phenanthroline, 3,6-DBSQ = anion-radical and 3,6-DBCat = dianion of 3,6-di-tert-butyl-o-benzoquinone). The abrupt interconversion of valence tautomers is observed in this temperature range: (phen)Co(3,6-DBCat)(3,6-DBSQ) ⇌ (phen)Co(3,6-DBSQ)2. Solving the problem of design of photo- (thermo-) actuators with preset parameters, the series of solid solutions of general formula (phen)x(bpy)1-xCo(3,6-DBSQ)2 was obtained and crystallized as thin elongated plates. Crystals of each solid solution demonstrate the maximal photomechanical response (bending) at a temperature close to its own valence tautomeric (VT) transition temperature. On the other hand, the VT transition temperature depends on the composition of the solid solution. So, by setting the composition of the solid solution, one can set the temperature of the photomechanical response. It is the first example of temperature-manageable photomechanical properties.


Rural-urban differences in factors associated with poor blood pressure control among outpatients.
The purpose of this study was to determine which patient-related factors are most strongly associated with having uncontrolled hypertension among outpatients. A sample of 300 outpatients with diagnosed hypertension from three different settings was reviewed, focusing on demographics, comorbidity, adherence, and treatment factors. Regression analyses were conducted to determine which factors were associated with poor BP control (> 140 mmHg systolic or > 90 mmHg diastolic). Those most strongly associated with blood pressure control were men (OR 2.04, 95% CI 1.17-3.55) living in a rural setting (OR 0.30, 95% CI 0.16-0.55). Age, race, total number of medicines, number of visits, and the number of comorbidities were not significantly associated with poor blood pressure control in this population. Being urban and male are strongly associated with uncontrolled hypertension. Public health blood pressure control efforts in the Southeast region should be directed toward this population.


Cost and usage of health sciences libraries: economic aspects.
A study of ninety-five health sciences libraries, obtaining nearly 24,000 user responses, provides estimates of the national cost of library services through the three principal services of circulation, reference, and in-house use; and for four types of users: persons interested in patient care, those interested in research, those involved in education, and others. Unit costs of the three principal services are reported and differences in their relative importance are described. National totals for nine classes of libraries are reported as well as costs by service, user, and function: patient care, research, education, or other. The national expenditure in 1982 was approximately $365 million. The study establishes a method for obtaining results that can be compared and combined across libraries.


Unilateral absent pulmonary perfusion due to bronchogenic carcinoma.
Ventilation-perfusion lung scans are commonly done in the diagnosis of pulmonary thromboembolic disease. We describe a patient in whom absent perfusion involving an entire lung was due to bronchogenic carcinoma. Echocardiography and chest computed tomography were essential tests in evaluating a nonembolic etiology.


Pneumoretroperitoneum following acupuncture.
Pneumoretroperitoneum is a rare event. It can be associated with infection, trauma, and medical interventions such as endoscopic procedures. Acupuncture is generally regarded as a safe procedure, yet cases of iatrogenic complications related with acupuncture have been reported. This report describes a case of pneumoretroperitoneum that developed after acupuncture. A 25-year-old female patient had been treated with acupuncture for her low back pain. Fever and right flank pain developed thereafter. Abdominal plain radiography and computed tomography (CT) disclosed retroperitoneal air along the right psoas muscle. After treatment with antibiotics and analgesics for a week, she was transferred to our hospital. The pneumoretroperitoneum disappeared on the follow-up abdominal CT. This is the first report of pneumoretroperitoneum following acupuncture.


Does autocatalytic amplification of maturation-promoting factor (MPF) exist in mammalian oocytes?
The method of polyethylene-glycol-induced fusion of mammalian oocytes was applied to study maturation-promoting factor (MPF) activity. After homologous fusions of one maturing--late diakinesis (LD), metaphase I (MI)--pig or mouse oocyte to one, two, or three immature-germinal vesicle (GV)--oocytes, giant cells were cultured in control or cycloheximide supplemented medium for 3 hours. The occurrence of germinal vesicle breakdown (GVBD) and premature chromosome condensation (PCC) served as a control of MPF activity. In giant cells composed of one maturing and one, two or three immature oocytes, GVBD and PCC were observed in all cases after cultivation in the control medium. In the presence of cycloheximide, the completion of GVBD and PCC remained high when one maturing and one immature oocyte were fused (83.7% and 95.7% of GVBD in pig and mouse, respectively). However, in giant cells composed of one maturing and up to three immature oocytes, all GVs were broken down only occasionally (4.8% and 11.7% in pig and mouse, respectively). These results suggest that in pig and mouse oocytes MPF does not amplify autocatalytically, but requires active protein synthesis for its production.


Ligand fishing of anti-neurodegenerative components from Lonicera japonica using magnetic nanoparticles immobilised with monoamine oxidase B.
In this work, monoamine oxidase B was immobilised onto magnetic nanoparticles to prepare a new type of affinity solid-phase extraction adsorbent, which was used to extract the possible anti-neurodegenerative components from the Lonicera japonica flower extracts. Coupled with high-performance liquid chromatography with mass spectrometry, two monoamine oxidase B ligands were fished-out and identified as isochlorogenic acid A and isochlorogenic acid C, which were found to be inhibitors of the enzyme for the first time, with similar half maximal inhibitory concentration values of 29.05 ± 0.49 and 29.77 ± 1.03 μM, respectively. Furthermore, equilibrium-dialysis dissociation assay of enzyme-inhibitor complex showed that both compounds have reversible binding patterns to monoamine oxidase B, and kinetic analysis demonstrated that they were mixed-type inhibitors for monoamine oxidase B, with Ki and Kis values of 9.55 and 37.24 μM for isochlorogenic acid A, 9.53 and 35.50 μM for isochlorogenic acid C, respectively. The results indicated that isochlorogenic acid A and isochlorogenic acid C were the major active components responsible for the anti-degenerative activity of the flowers of L. japonica, while magnetic nanoparticles immobilised monoamine oxidase B could serve as an efficient solid-phase extraction adsorbent to specifically extract monoamine oxidase B inhibitors from complex herbal extracts.


Identification of common non-coding variants at 1p22 that are functional for non-syndromic orofacial clefting.
Genome-wide association studies (GWAS) do not distinguish between single nucleotide polymorphisms (SNPs) that are causal and those that are merely in linkage-disequilibrium with causal mutations. Here we describe a versatile, functional pipeline and apply it to SNPs at 1p22, a locus identified in several GWAS for non-syndromic cleft lip with or without cleft palate (NS CL/P). First we amplified DNA elements containing the ten most-highly risk-associated SNPs and tested their enhancer activity in vitro, identifying three SNPs with allele-dependent effects on such activity. We then used in vivo reporter assays to test the tissue-specificity of these enhancers, chromatin configuration capture to test enhancer-promoter interactions, and genome editing in vitro to show allele-specific effects on ARHGAP29 expression and cell migration. Our results further indicate that two SNPs affect binding of CL/P-associated transcription factors, and one affects chromatin configuration. These results translate risk into potential mechanisms of pathogenesis.


Shear Stress and ROS Dual-Responsive RBC-Hitchhiking Nanoparticles for Atherosclerosis Therapy.
Atherosclerosis (AS), a leading cause of death worldwide, is a chronic inflammatory disease rich in lipids and reactive oxygen species (ROS) within plaques. Therefore, lowering lipid and ROS levels is effective in treating AS and reducing AS-induced mortality. In this study, an intelligent biomimetic drug delivery system that specifically responded to both shear stress and ROS microenvironment was developed, consisting of red blood cells (RBCs) and cross-linked polyethyleneimine nanoparticles (SA PEI) loaded with a lipid-lowering drug simvastatin acid (SA), and RBCs were self-assembled with SA PEI to obtain biresponsive SA PEI@RBCs for the treatment of AS. SA PEI could achieve sustained release of SA in response to ROS and reduce ROS and lipid levels to achieve the purpose of treating AS. Shear stress model experiments showed that SA PEI@RBCs could respond to the high shear stress level (100 dynes/cm2) at plaques, realizing the desorption and enrichment of SA PEI and improving the therapeutic efficiency of SA PEI@RBCs. In vitro and in vivo experiments have confirmed that SA PEI@RBCs exhibits better in vivo safety and therapeutic efficacy than SA PEI and free SA. Therefore, shaping SA PEI@RBCs into a biomimetic drug delivery system with dual sensitivity to ROS and shear stress is an effective strategy and treatment to facilitate their delivery into plaques.


Countercurrent arterial contrast echocardiography in the assessment of left to right ductal shunting in preterm infants.
A method of performing contrast echocardiography for the assessment of left to right ductal shunting in infants in a neonatal intensive care unit is described. Echo contrast was obtained by countercurrent injection of a small volume of blood through a radial artery canula . The technique was simple and reliable in 32 infants and no serious adverse reactions were observed.


Key attributes of successful research institutes.
Science does not take place in a vacuum: The physical and social workplace has a profound influence on scientific discoveries. Everyone at a research institute can contribute to its scientific output and productivity, from faculty research groups to facilities and platforms staff to administration and corporate services. Although the researchers addressing exciting scientific questions are key, their efforts can be fostered and directed by the overarching strategy of the institute, interconnection with facilities and platforms, and strong and directed support of the administration and corporate services. Everybody counts and everybody should be empowered to contribute. But what are the characteristics that make scientific organizations and their people flourish? This Essay looks at the structure and culture of successful research institutes, laying out different operational strategies and highlighting points that need be taken into consideration during their implementation.