Contrast Dispersion Pattern and Efficacy of Corticosteroid at the Glenohumeral Joint in Adhesive Capsulitis.
Corticosteroid injection has a wide range of success in adhesive capsulitis but the reason for this has not yet been explained. We hypothesized that this difference might be due to the distribution of the corticosteroids injected into the joint cavity because particulate steroid deposits in the capsule and will not be moved over time by shoulder motion. The purpose of this study is to determine whether the therapeutic efficacy of particulate corticosteroid injection into the glenohumeral joint differs according to the dispersion pattern. Prospective evaluation. Outpatient clinics at a tertiary university hospital. Seventy-two patients diagnosed as having adhesive capsulitis received a corticosteroid injection at the glenohumeral joint. The posterior capsule and the subscapular bursa were selected as dispersion sites and the dispersion of contrast dye was expressed as a ratio (%). Two weeks and 3 months after the injection clinical improvement ("not improved," "slightly improved," "much improved"), numeric rating scale (NRS), and passive range of motions (PROM) were evaluated. The dispersion of the contrast dye was compared according to the clinical improvements by an analysis of variance test. Pearson correlation test was done to find the relationship between PROM and the dispersion and between change of NRS and the dispersion. The distribution in the subscapular area was 30.0% in the "much improved" group, 22.0% in the "slightly improved" group, and 37.1% in the "no improvement" group which was not significantly different (P = 0.179). Correlations between changes of NRS and the dye distribution were not statistically significant (P = 0.429 at 2 weeks and P = 0.629 at 3 months). The change of passive external rotation 3 months after the injection was significantly correlated with the dye distribution (P = 0.035). Because of diverse pathologic findings in adhesive capsulitis, further studies will be needed to address the effect of the dye distribution on the pain improvement according to pathologic findings revealed by magnetic resonance imaging (MRI). External rotation of the shoulder in adhesive capsulitis has greater improvement as the corticosteroid solutions injected into the glenohumeral joint are increasingly dispersed to the subscapularis area. However, this does not affect the pain improvement after the injection.


Global optimization of bimetallic cluster structures. II. Size-matched Ag-Pd, Ag-Au, and Pd-Pt systems.
Genetic algorithm global optimization of Ag-Pd, Ag-Au, and Pd-Pt clusters is performed. The 34- and 38-atom clusters are optimized for all compositions. The atom-atom interactions are modeled by a semiempirical potential. All three systems are characterized by a small size mismatch and a weak tendency of the larger atoms to segregate at the surface of the smaller ones. As a result, the global minimum structures exhibit a larger mixing than in Ag-Cu and Ag-Ni clusters. Polyicosahedral structures present generally favorable energetic configurations, even though they are less favorable than in the case of the size-mismatched systems. A comparison between all the systems studied here and in the previous paper (on size-mismatched systems) is presented.


[A case of recurrent small cell lung cancer with symptoms improved by nogitecan hydrochloride].
A 68-year-old woman with recurrent advanced small cell lung cancer (SCLC), previously treated with 7 courses of carboplatin + etoposide, 4 courses of cisplatin + irinotecan and radiotherapy (primary site and whole brain irradiation), received 3 courses of a single nogitecan hydrochloride i.v. bolus with 4 consecutive days of administration, for a total dose of 7.5 mg. MR-imaging revealed a response in the brain metastasis, and tumor markers (NSE and ProGRP) were improved after the first course. Headache, her main complaint, was also alleviated. These observations suggest that nogitecan hydrochloride alone might be useful for treatment of recurrent SCLC in cases of poor performance status (PS), especially when the patient requires remission of symptoms.


Cyclization of short DNA fragments and bending fluctuations of the double helix.
Cloutier and Widom [Cloutier, T. E. & Widom, J. (2004) Mol. Cell 14, 355-362] recently reported that the cyclization efficiency of short DNA fragments, about 100 bp in length, exceeds theoretical expectations by three orders of magnitude. In an effort to resolve this discrepancy, we tried modifying the theory. We investigated how the distribution of the angles between adjacent base pairs of the double helix affects the cyclization efficiency. We found that only the incorporation of sharp kinks in the angle distribution provides the desired increase of the cyclization efficiency. We did not find a model, however, that fits all cyclization data for DNA fragments of different lengths. Therefore, we carefully reinvestigated the cyclization of 100-bp DNA fragments experimentally and found their cyclization efficiency to be in remarkable agreement with the traditional model of DNA bending. We also found an explanation for the discrepancy between our results and those of Cloutier and Widom.


Effects of nonoxynol-9 (N-9) on sperm functions: systematic review and meta-analysis.
To summarize the currently available phase I and II clinical trials of the effects of nonoxynol-9 (N-9) on human sperm structure and functions. A systematic review and meta-analysis aiming to evaluate the spermicidal activity of N-9 on motility, was conducted in PubMed, EMBASE, and Cochrane databases by 10 March 2021. The counted numbers of progressive motile (PR) sperm in cervical mucus and the vanguard sperm penetration distances were analyzed. Other effects on sperm structures and physiological activities were reviewed as well. In the pooled results, percentages or counted numbers of PR sperm decreased after the treatment of N-9. Vanguard sperm penetration distance was shortened in treated groups. N-9 has been confirmed to damage the structures of sperm, as well as other organelles like acrosome and mitochondria. The physiological activities such as generation of reactive oxygen species, superoxide dismutase activity, acrosin activity, and hemizona binding were all inhibited in the reviewed studies. N-9 has several impacts on sperm owing to its potency in reducing sperm motility and cervical mucus penetration, as well as other functional competencies. Nonoxynol-9 (N-9) has been used worldwide as a spermicide to kill sperm for more than 60 years but can cause side effects including vaginal irritation and can increase the rate of contraceptive failure. A detailed analysis of published literature aiming to evaluate the spermicidal activity of N-9 on sperm was carried out. In the pooled results, N-9 reduced the number of active sperm and the distance they traveled. It also caused damage to the structures of sperm and to the way the sperm acted and interacted with the egg. In conclusion, N-9 impacts on sperm in a number of ways that lead to sperm death and dysfunction.


Increased nausea and vomiting induced by naloxone in patients receiving cancer chemotherapy.
To evaluate the role of endogenous opiates in chemo-therapy-induced nausea and vomiting, the narcotic-antagonist naloxone was administered to six pediatric patients receiving cancer chemotherapy. Naloxone was administered by continuous intravenous (i.v.) infusion after randomized, double-blind controlled assignment at a dose of 0, 10 or 40 micrograms/kg/h for 12 h. Each patient was studied for four consecutive and identical courses of chemotherapy (eight courses for each naloxone dose or 24 courses in all). A dose-related increase in nausea (nausea score 2.5 +/- 2.24, 3.83 +/- 2.73, and 5.75 +/- 2.86/12 h, p = 0.003), vomiting (emetic events 6.0 +/- 7.50, 8.08 +/- 6.71, and 10.3 +/- 8.91/12 h, p = 0.035), and patient aversion (course preference rank 1.5 +/- 0.45, 2.83 +/- 1.17, and 3.25 +/- 0.42/4 courses, p = 0.014) was observed. The infusion of naloxone in the absence of chemotherapy was without effect. These results support a role for endogenous opiates in regulating chemotherapy-induced nausea and vomiting, and further suggest that narcotic agents may be effective antiemetics in this setting.


Adenosine-mediated autoregulation of retinal arteriolar tone in the piglet.
To determine if the purine vasodilator adenosine participates in mediating autoregulatory dilations of the retinal microcirculation in vivo. The retinal microcirculation of isoflurane-anesthetized newborn pigs was observed by videomicroscopy (x310). Systemic hypoxia (PaO2 = 24 +/- 1 mm Hg; n = 8) or hemorrhagic hypotension (MABP = 41 +/- 1 mm Hg; n = 5) was induced, and the effect of intravitreal microsuffusion of 0.4 nmol of the adenosine receptor antagonist 8-sulfophenyltheophylline (8SPT) on retinal arteriolar dilations resulting from these stimuli were measured. The effect of potentiation of endogenous interstitial adenosine concentrations with 0.2 nmol 4-nitrobenzyl-6-thioinosine (NBTI) on the response to hypotension (MABP = 43 +/- 2 mm Hg; n = 4) was also determined. The significant vasodilatative response of the retinal arterioles to systemic hypoxia (36 +/- 8% increase in diameter above baseline; P = 0.0012) was attenuated 55% (P < 0.0001) by the adenosine antagonist 8SPT. Similarly, the significant arteriolar vasodilation induced by systemic hypotension (29 +/- 3% increase in diameter; P < 0.0001) was inhibited 76% by 8SPT (P = 0.0002). When adenosine reuptake was inhibited with NBTI, the arteriolar dilation induced by hypotension (32 +/- 5% increase in diameter; P = 0.0234) was potentiated 100% (P = 0.0117). Our finding that inhibition or potentiation of endogenous adenosine action uniquely affected retinal arteriolar dilatative responses to hypoxia and hypotension suggests that adenosine is a key participant in mediating autoregulatory adjustments in retinal blood flow in the eye of the newborn.


Controlling Solution-State Aggregation and Solid-State Microstructures of Conjugated Polymers by Tuning Backbone Conformation.
Molecular ordering of conjugated polymers both in solution-state aggregates and in solid-state microstructures is a determining factor of the charge transport properties in optoelectronic devices. However, the effect of backbone conformation in conjugated polymers on assembly structures is still unclear. Herein, to understand such backbone conformation effect, three novel chlorinated benzodifurandionge-based oligo(p-phenylene vinylene) (BDOPV) polymers are systematically developed. These BDOPV-based polymers exhibit significantly twisted backbone conformation (near 90° interunit torsion angle) between conjugated units, which can prevent polymer chains from forming ordered assembly structures by increasing conformational energy penalty in closely packed chains. A higher rotational barrier of the torsion angle would further prevent polymer chains from assembling, finally resulting in nonaggregated chains in solution and highly disordered solid-state packing structures. This work will deepen the understanding of the relationship between polymer backbone conformation and assembly structures, contributing to the exploration of the structure-property relationship of polymers.


NaIO4/LiBr-mediated diastereoselective dihydroxylation of olefins: a catalytic approach to the Prevost-Woodward reaction.
[reaction: see text] LiBr catalyzes efficiently the dihydroxylation of alkenes to afford syn and anti diols with excellent diastereoselectivity depending upon the use of NaIO(4) (30 mol %) or PhI(OAc)(2) (1 equiv), respectively, as the oxidants. The oxidation of non-benzylic halides has been achieved for the first time to afford the corresponding diols in excellent yields.


Management of a patient with hereditary angioneurotic edema.
Patients with a history of hereditary angioneurotic edema can adequate and safely have nonelective surgical procedures performed with proper preoperative and postoperative management. Deficient amounts of C1 esterase inhibitor can be replaced with fresh frozen plasma; capillary permeability and spreading edema can be prevented with antifibrinolytic agents such as Amicar. Once edema has occurred peripherally and no laryngeal symptoms are present, conservative treatment is advisable. When epiglottic and laryngeal edema occurs, intubation or tracheostomy is preferred for maintenance of airway until the edema subsides. During oral surgical procedures, minimal surgical trauma must be achieved. Edema that involves the airway presents the greatest danger to patients. These attacks are usually associated with dental or some sort of oral or pharyngeal manipulation.


Detecting high-resolution polymorphisms in human coding loci by combining PCR and single-strand conformation polymorphism (SSCP) analysis.
A strategy is described that allows the development of polymorphic genetic markers to be characterized in individual genes. Segments of the 3' untranslated regions are amplified, and polymorphisms are detected by digestion with frequently cutting enzymes and with the detection of single-stranded conformation polymorphisms. This allows these genes, or DNA segments, to be placed on the linkage maps of human chromosomes. Polymorphisms in two genes have been identified using this approach. A HaeIII polymorphism was detected in the KIT proto-oncogene, physically assigned to chromosome 4q11-12. This polymorphism is linked to other chromosome 4p markers and is in linkage disequilibrium with a HindIII polymorphism previously described at this locus. We have also identified in the insulin-like growth factor1 receptor gene (IGF1R) a 2-bp deletion that is present at a frequency of .25 in the Caucasian population. Pedigree analysis with this insertion/deletion polymorphism placed the IGF1R gene at the end of the current linkage map of chromosome 15q, consistent with the physical assignment of 15q2526. Thus, polymorphisms in specific genes can be used to related the physical, genetic, and comparative maps of mammalian genomes and to simplify the testing of candidate genes for human diseases.


Regional and subcellular distribution of soluble aminopeptidase in the human and the rat brain: a comparative study.
In an attempt to elucidate the cellular function of the soluble aminopeptidases, we have analysed their activity in several subcellular fractions (synaptosomal, mitochondrial, microsomal, nuclear and cytosolic fraction) and in different areas (amygdala, hypothalamus, hippocampus, striatum, frontal cortex, occipital cortex and parietal cortex) of the human and the rat brain. The enzymes assayed in this study were five cytosolic aminopeptidases identified inmammalian brain tissues: alanyl-aminopeptidase, arginyl-aminopeptidase, leucyl-aminopeptidase, pyroglutamyl-peptidase I and aspartyl-aminopeptidase. The regional comparative study revealed significantly higher activities of alanyl-aminopeptidase activity in the human brain, with arginyl-aminopeptidase activities being higher in the rat brain. In the subcellular study, while the alanyl- and arginyl-aminopeptidase activities were quite homogeneous in all the subcellular fractions, the leucyl-aminopeptidase, pyroglutamyl-peptidase I and aspartyl-aminopeptidase activities were significantly higher in the synaptosomal fraction. The differential distribution of these enzymes could suggest that these activities have different functions in the distinct subcellular structures of the human and the rat brain.


Effect of acute hypoxia and hypercapnic acidosis on the development of acetylstrophanthidin-induced arrhythmias.
The effect of acutely induced hypoxia, hypercapnic acidosis, and the combination of the two on the amount of acetylstrophanthidin (AS) required to produce cardiac arrhythmias was determined in anesthetized dogs. Each animal was studied during ventilation with room air and again during ventilation with gas mixtures of appropriate concentrations; 24 hr separated the study periods. AS was infused intravenously at a rate of 5 mug/kg per min. Significantly less AS was required to produce arrhythmias during hypoxia and hypercapnic acidosis together than during the period with normal arterial Po(2), Pco(2), and pH (10 animals). Included in this group were two animals which had undergone previous bilateral adrenalectomy and four animals in which heart rate was maintained at the same frequency during both study periods. A significant reduction in the toxic dose of AS also was demonstrated in eight animals, two with constant heart rate, during hypoxia with normal arterial Pco(2) and pH. Hypercapnic acidosis alone (eight animals) did not significantly alter the toxic dose of AS. After the administration of propranolol (six animals) or hexamethionium (six animals), no significant difference was observed between the toxic dose of AS during hypoxia and that during ventilation with room air. Thus although hypoxia and hypercapnic acidosis together do reduce the amount of AS required to produce arrhythmias, it is the hypoxia which exerts the predominant effect on the development of this increased sensitivity to AS. Furthermore, this effect of hypoxia occurs primarily as a result of reflexly augmented sympathetic stimulation of the heart.


Cerebrospinal Fluid Biomarkers for Alzheimer's Disease: Their Role in Clinical Chemistry.
In view of current (AChE inhibitors) and future (e.g. anti-Aβ aggregators), development and evaluation of cerebrospinal fluid (CSF) biomarkers for Alzheimer's disease (AD) has become a rapidly growing research field. Diagnostic biomarkers for AD would be especially valuable as aids in the diagnosis early in the course of the disease, when correct diagnosis is difficult, and when therapeutic compounds have the greatest potential of being effective. This paper reviews CSF biomarkers for AD, with emphasis on their role in the clinical diagnosis, and methodological aspects of importance for developing such analyses. Today, two biochemical markers, CSF-tau and CSF-Aβ42, perform satisfactory enough to have a role in the clinical workup of patients dementia, if used together with the cumulative information from clinical information and brain-imaging techniques. These markers are especially useful to discriminate early or incipient AD from age-associated memory impairment, depression, and some secondary dementias.


Heparin-induced inhibitory effects of a prothrombin complex concentrate on global tests of haemostasis.
Prothrombin complex concentrates (PCC) have been used as bypassing agents for the treatment of haemophilia A patients with inhibitor as well as for replacement therapy in congenital and acquired deficiencies of vitamin-K-dependent clotting factors. The efficacy of PCC is variable, however, especially during long-term and high-dose use, and all currently available products of this nature contain heparin. We have examined the haemostatic properties of PCC using reconstituted whole blood made by mixing coagulation-factor-deficient plasma and washed blood cells. In rotation thromboelastometry (ROTEM), the recommended therapeutic dose of Proplex ST corrected the abnormal patterns. At higher concentrations, however, the ROTEM patterns regressed. In addition, specific assays of coagulation factors appeared unreliable in the presence of 2.5 U/ml Proplex ST; the abnormalities were corrected when protamine sulfate was added. The findings suggest that the presence of heparin in PCC might have a greater effect on global haemostasis. Careful attention to the anticoagulant effect as well as thrombogenicity of PCC is required. Monitoring therapy using such as ROTEM analysis could be highly informative.


Adenosine A2A Receptor Signaling in the Immunopathogenesis of Experimental Autoimmune Encephalomyelitis.
Our increasing appreciation of adenosine as an endogenous signaling molecule that terminates inflammation has generated excitement regarding the potential to target adenosine receptors (ARs) in the treatment of multiple sclerosis (MS), a disease of chronic neuroinflammation. Of the four G protein-coupled ARs, A2ARs are the principal mediator of adenosine's anti-inflammatory effects and accordingly, there is a growing body of evidence surrounding the role of A2ARs in experimental autoimmune encephalomyelitis (EAE), the dominant animal model of MS. Such evidence points to a complex, often paradoxical role for A2ARs in the immunopathogenesis of EAE, where they have the ability to both exacerbate and alleviate disease severity. This review seeks to interpret these paradoxical findings and evaluate the therapeutic promise of A2ARs. In essence, the complexities of A2AR signaling arise from two properties. Firstly, A2AR signaling downregulates the inflammatory potential of TH lymphocytes whilst simultaneously facilitating the recruitment of these cells into the CNS. Secondly, A2AR expression by myeloid cells - infiltrating macrophages and CNS-resident microglia - has the capacity to promote both tissue injury and repair in chronic neuroinflammation. Consequently, the therapeutic potential of targeting A2ARs is greatly undermined by the risk of collateral tissue damage in the periphery and/or CNS.


Central voice production and pathophysiology of spasmodic dysphonia.
Our ability to speak is complex, and the role of the central nervous system in controlling speech production is often overlooked in the field of otolaryngology. In this brief review, we present an integrated overview of speech production with a focus on the role of central nervous system. The role of central control of voice production is then further discussed in relation to the potential pathophysiology of spasmodic dysphonia (SD). Peer-review articles on central laryngeal control and SD were identified from PUBMED search. Selected articles were augmented with designated relevant publications. Publications that discussed central and peripheral nervous system control of voice production and the central pathophysiology of laryngeal dystonia were chosen. Our ability to speak is regulated by specialized complex mechanisms coordinated by high-level cortical signaling, brainstem reflexes, peripheral nerves, muscles, and mucosal actions. Recent studies suggest that SD results from a primary central disturbance associated with dysfunction at our highest levels of central voice control. The efficacy of botulinum toxin in treating SD may not be limited solely to its local effect on laryngeal muscles and also may modulate the disorder at the level of the central nervous system. Future therapeutic options that target the central nervous system may help modulate the underlying disorder in SD and allow clinicians to better understand the principal pathophysiology. NA.Laryngoscope, 128:177-183, 2018.


The novel immunotherapeutic oligodeoxynucleotide IMT504 protects neutropenic animals from fatal Pseudomonas aeruginosa bacteremia and sepsis.
IMT504 is a novel immunomodulatory oligonucleotide that has shown immunotherapeutic properties in early preclinical and clinical studies. IMT504 was tested in a neutropenic rat model of Pseudomonas aeruginosa bacteremia and sepsis. This animal system recapitulates many of the pathological processes found in neutropenic patients with Gram-negative, bacterial infections. The research was conducted in the setting of an academic research laboratory. The test subjects were Sprague-Dawley rats. Animals were rendered neutropenic by administration of cyclophosphamide, colonized with P. aeruginosa by oral feeding, and then randomized to receive IMT504 over a range of doses and treatment regimens representing early and late therapeutic interventions. IMT504 immunotherapy conferred a significant survival advantage over the 12-day study period compared with the results seen with placebo-treated animals when the therapy was administered at the onset of neutropenia and even in the absence of antibiotics and after the onset of fever and systemic infection. Notably, even late salvage IMT504 monotherapy was highly effective (13/14 surviving rats with IMT504 therapy versus 2/14 controls, P=<0.001). Moreover, late salvage IMT504 monotherapy was as effective as antibiotic therapy (13/14 surviving rats versus 21/21 rats, P=0.88). In addition, no antagonism or loss of therapeutic efficacy was noted with combination therapy of IMT504 plus antibiotics. IMT504 immunotherapy provides a remarkable survival advantage in bacteremia and sepsis in neutropenic animals and deserves further study as a new treatment option in patients with, or at risk for, severe Gram-negative bacterial infections and sepsis.


BRCA1 associates with the inactive X chromosome in late S-phase, coupled with transient H2AX phosphorylation.
The BRCA1 tumor suppressor gene encodes an E3-ubiquitin ligase that has been implicated in several distinct biochemical processes. As the cell cycle progresses, BRCA1 proteins interact transiently with nuclear foci containing DNA replication and DNA double-strand repair machinery. A hallmark of these foci is the presence of S139 phosphorylated histone H2AX. BRCA1 was recently shown to associate with facultative heterochromatin at the inactive X chromosome (Xi), where it may play a role in maintaining gene silencing. As the kinetics of this interaction has not been described, we sought to establish whether association of BRCA1 with the Xi also correlated with replication. Here we demonstrate that the interaction of BRCA1 and the Xi is transient, occurring during late S-phase. This interaction is concomitant with the presence of distinct foci of S139 phospho-H2AX and specifically corresponds with late replication of the Xi. BRCA1 and phospho-H2AX appear on the Xi immediately adjacent to CAF-1, a known marker of replication fork activity. Taken together, these data implicate BRCA1 and the H2AX kinase in replication of facultative heterochromatin on the Xi, most likely in a fashion similar to that performed at sites of DNA replication and double-strand break repair observed on somatic chromosomes.


[Urinary enzyme excretion in diseases of the internal organs].
In a survey the present possibilities are outlined to get knowledge about diseases of inner organs with the help of enzyme determinations in the urine. Here it is remarkable that changes of the enzyme excretion appear not only in renal disease with acute renal failure, pyelonephritis, glomerulonephritis, renal infarction and nephroptosis but are also to be observed in primarily extrarenal diseases such as diabetes mellitus, hyperthyroidism, thesaurismoses, myocardial infarction, hypertension, acute pancreatitis, epidemic hepatitis, liver cirrhosis, obstructive jaundice and rheumatoid arthritis. The causes of the changes of enzyme excretions are various. Since enzymes of different origin and localisation behave themselves variably, the simultaneous determination of a brush border marker (e.g. alanine aminopeptidase), a lysosomal enzyme (e.g. beta-glucuronidase or N-acetyl glucosaminidase) and a low molecular enzyme (e.g. lysozyme) is of use for the recognition of renal alterations. By the control of activities of urinary enzymes it is possible to get without risk informations about pathobiochemical processes in the kidney which are not to be gained by means of other methods.


An Evaluation of Cognitive Behavioral Therapy for Substance Use Disorder: A Systematic Review and Application of the Society of Clinical Psychology Criteria for Empirically Supported Treatments.
Cognitive behavioral therapy (CBT) is a commonly used treatment for substance use disorders (SUDs) but has not been evaluated using the American Psychological Association's "Tolin Criteria" for determining the empirical basis of psychological treatments. The current systematic review evaluated five meta-analyses of CBT for SUD. One meta-analysis had sufficient quality to be considered in the evaluation of effect sizes. CBT produced small to moderate effects on substance use when compared to inactive treatment and was most effective at early follow-up (1-6 months post-treatment) compared to late follow-up (8+ months post-treatment). Sensitivity analyses including all five meta-analyses found similar results. A "strong recommendation" was provided for CBT as an empirically supported treatment for SUD, based on effects on substance use, quality of evidence, and consideration of contextual factors (e.g., efficacy in diverse populations).


Hemodynamics in the mouse aortic arch as assessed by MRI, ultrasound, and numerical modeling.
Mice are widely used to study arterial disease in humans, and the pathogenesis of arterial diseases is known to be strongly influenced by hemodynamic factors. It is, therefore, of interest to characterize the hemodynamic environment in the mouse arterial tree. Previous measurements have suggested that many relevant hemodynamic variables are similar between the mouse and the human. Here we use a combination of Doppler ultrasound and MRI measurements, coupled with numerical modeling techniques, to characterize the hemodynamic environment in the mouse aortic arch at high spatial resolution. We find that the hemodynamically induced stresses on arterial endothelial cells are much larger in magnitude and more spatially uniform in the mouse than in the human, an effect that can be explained by fluid mechanical scaling principles. This surprising finding seems to be at variance with currently accepted models of the role of hemodynamics in atherogenesis and the known distribution of atheromatous lesions in mice.


[Morbidity of foreskin reconstruction in distal hypospadias repair surgery].
Hypospadias is almost constantly associated with an abnormality of the prepuce, resulting in incomplete prepuce. In the context of distal hypospadias repair surgery, prepuce reconstruction is an alternative to circumcision. The authors report their experience of this operation and analyze its specific morbidity. Single-center retrospective study of 316 prepuce reconstructions performed in the context of distal hypospadias surgery between 1996 and 2004. The median age at the time of surgery was 12.1 months. The prepuce reconstruction technique was based on the principles of Righini preputioplasty. Urethroplasty was performed according to the tubularized urethral plate (Duplay-Snodgrass) technique in the majority of children (204/316, 65%). No urethral catheter was left in place in 293 children (93%). The operation was performed as an outpatient procedure in 245 cases (78%). Partial or complete disunion of the reconstructed prepuce was observed in 18 children (6%), mainly early in the authors' experience, and nine of these 18 cases occurred in a more general context of failure of hypospadias repair surgery (urethrocutaneous fistula). Secondary phimosis was observed in 40 cases, 12 months after the operation. Topical corticosteroids (betamethasone 1.0% cream) allowed normal foreskin retraction in 26 out of 30 cases (85%). Prepuce reconstruction performed in the context of distal hypospadias repair surgery is responsible for a low rate of specific morbidity. If the objective of distal hypospadias surgery is to restore a penis with an appearance as normal as possible, prepuce reconstruction should constitute a key element of the final result.


Nickel-induced heritable alterations in retroviral transforming gene expression.
Determination of the mutagenic effects of carcinogenic nickel compounds has been difficult because, like many metals, nickel is poorly or nonmutagenic in procaryotic mutagenicity assays. We attempted to characterize nickel-induced genetic lesions by assessing the effect of nickel chloride on the conditionally defective expression of the v-mos transforming gene in normal rat kidney cells infected with the Murine sarcoma virus mutant ts110 (MuSVts110) retrovirus. MuSVts110 contains an out-of-frame gag gene-mos gene junction that prevents the expression of the v-mos gene at the nonpermissive temperature (39 degrees C). In MuSVts110-infected cells (6m2 cells) grown at 33 degrees C, however, this defect can be suppressed by a splicing event that restores the mos reading frame, allowing the expression of a gag-mos fusion protein which induces the transformed phenotype. The capacity to splice the viral transcript at 33 degrees C, but not at 39 degrees C, is an intrinsic property of the viral RNA. This property allowed us to target the MuSVts110 genome using a positive selection scheme whereby nickel was used to induce genetic changes which resulted in expression of the transformed phenotype at 39 degrees C. We treated 6m2 cells with NiCl2 and isolated foci consisting of cells which had reverted to the transformed phenotype at 39 degrees C. We found that brief nickel treatment increased the reversion frequency of 6m2 cells grown at 39 degrees C sevenfold over the spontaneous reversion frequency. The nickel-induced revertants displayed the following heritable characteristics: They stably maintained the transformed phenotype at 39 degrees C; unlike the MuSVts110 RNA in 6m2 cells, the nickel-induced revertant viral RNA could be spliced efficiently at 39 degrees C; as a consequence of the enhanced accumulation of spliced viral RNA, the nickel-induced revertants produced substantial amounts of the transforming v-mos protein P85gag-mos at 39 degrees C; the nickel-induced revertant P85gag-mos serine kinase, like the parental 6m2 P85gag-mos kinase, was found to be rapidly inactivated at 39 degrees C; however, in the nickel-induced revertants, overproduction of P85gag-mos allowed the transformed state to be maintained; and even though viral RNA processing was much changed, no rearrangements of the viral DNA in the nickel-induced revertant cells were detected by partial restriction analysis.


Reverse transcriptase viral load correlates with RNA in SIV/SHIV-infected macaques.
Monitoring of viral load in macaques has usually been carried out using in-house PCR-based methods. A novel viral load (VL) kit (ExaVir Load) based on the measurement of lentivirus reverse transcriptase (RT) activity provides a potential alternative to methods that measure plasma viral RNA. RT is a fundamental and conserved activity of all retroviruses and the method should theoretically detect RT from all lentiviruses. To test this we compared VL measured by a commercially available RT kit with an in-house QC RT-PCR in macaques infected with SIV and SHIV. Both RT and RNA levels were measured over time in both sets of macaques. Results indicated that the relationship between both tests was strong for SIV and SHIV (r = 0.95 and r = 0.92, p < 0.0001, respectively). The VL trends also followed each other, indicating that both techniques measured the same process of viral replication. Furthermore, the RT load obtained using standardized control plasma samples supplied by NIBSC gave values close to the designated VL. However, when comparing RT load with QC RT-PCR a consistently three to five time higher level was obtained with the RT assay, highlighting potential differences in assay calibration. Even so, the data suggest that the RT assay is both sensitive and robust for use in the SIV/SHIV macaque model, particularly where molecular-based assays for SIV VL determinations are not easily available. The assay is also a commercially available kit and hence has the potential to reduce the variability seen between laboratories using in-house PCR.


Differences between patients with a preserved and a depressed left ventricular function: a report from the EuroHeart Failure Survey.
Due to a lack of clinical trials, scientific evidence regarding the management of patients with chronic heart failure and preserved left ventricular function (PLVF) is scarce. The EuroHeart Failure Survey provided information on the characteristics, treatment and outcomes of patients with PLVF as compared to patients with a left ventricular systolic dysfunction (LVSD). We performed a secondary analysis using data from the EuroHeart Failure Survey, only including patients with a measurement of LV function (n = 6806). We selected two groups: patients with LVSD (54%) and patients with a PLVF (46%). Patients with a PLVF were, on average, 4 years older and more often women (55% vs. 29%, respectively, p < 0.001) as compared to LVSD patients, and were more likely to have hypertension (59% vs. 50%, p < 0.001) and atrial fibrillation (25% vs. 23%, p = 0.01). PLVF patients received less cardiovascular medication compared to PLVF patients, with the exception of calcium antagonists. Multivariate analysis revealed that LVSD was an independent predictor for mortality, while no differences in treatment effect on mortality between the two groups was observed. A sensitivity analysis, using different thresholds to separate patients with and without LVSD revealed comparable findings. In the EuroHeart Failure Survey, a high percentage of heart failure patients had PLVF. Although major clinical differences were seen between the groups, morbidity and mortality was high in both groups.


Influenza and COVID-19 Vaccination Coverage Among Health Care Personnel - United States, 2021-22.
The Advisory Committee on Immunization Practices (ACIP) and CDC recommend that all health care personnel (HCP) receive annual influenza vaccination to reduce influenza-related morbidity and mortality among these personnel and their patients (1). ACIP also recommends that all persons aged ≥6 months, including HCP, be vaccinated with COVID-19 vaccines and remain up to date (2,3). During March 29-April 19, 2022, CDC conducted an opt-in Internet panel survey of 3,618 U.S. HCP to estimate influenza vaccination coverage during the 2021-22 influenza season as well as receipt of the primary COVID-19 vaccination series and a booster dose. Influenza vaccination coverage was 79.9% during the 2021-22 season, and 87.3% of HCP reported having completed the primary COVID-19 vaccination series; among these HCP, 67.1% reported receiving a COVID-19 booster dose. Among HCP, influenza, COVID-19 primary series, and COVID-19 booster dose vaccination coverage were lowest among assistants and aides, those working in long-term care (LTC) or home health care settings, and those whose employer neither required nor recommended the vaccines. Overall, employer requirements for influenza and COVID-19 primary series vaccines were reported by 43.9% and 59.9% of HCP, respectively; among HCP who completed the primary series of COVID-19 vaccines, 23.5% reported employer requirements for COVID-19 booster vaccines. Vaccination coverage for all three vaccine measures was higher among HCP who reported employer vaccination requirements and ranged from 95.8% to 97.3% for influenza, 90.2% to 95.1% for COVID-19 primary series, and 76.4% to 87.8% for COVID-19 booster vaccinations among HCP who completed the primary series of COVID-19 vaccines, by work setting. Implementing workplace strategies demonstrated to improve vaccination coverage among HCP, including vaccination requirements or active promotion of vaccination, can increase influenza and COVID-19 vaccination coverage among HCP and reduce influenza and COVID-19-related morbidity and mortality among HCP and their patients (4).


Fragmented inclusion: Community participation and lesbian, gay, bisexual, trans, and queer people with diagnoses of schizophrenia and bipolar disorder.
Community participation is often cited as a crucial component of wellness for people with mental health diagnoses. Few studies explore community participation from the perspective of lesbian, gay, bisexual, trans, and queer (LGBTQ) people with diagnoses of schizophrenia and bipolar disorder. This article describes an in-depth qualitative study with 16 LGBTQ people; 18 social service workers; and 2 key informants in Toronto, Ontario that examined access to communities for LGBTQ people with mental health diagnoses. Results indicate that community participation is particularly relevant to this group given the functions of communities for marginalized people as a source of support and resistance. However, the participants faced barriers to accessing support and creating social networks due to the lack of intersectional inclusion in various contexts, including LGBTQ communities and mental health/mad communities. (PsycINFO Database Record


The effect of progressive resistance training on aerobic fitness and strength in adults with coronary heart disease: A systematic review and meta-analysis of randomised controlled trials.
Design We aimed to evaluate the effect of progressive resistance training on cardiorespiratory fitness and muscular strength in coronary heart disease, when compared to control or aerobic training, and when combined with aerobic training. Secondary aims were to evaluate the safety and efficacy of progressive resistance training on other physiological and clinical outcomes. Methods and results Electronic databases were searched from inception until July 2016. Designs included progressive resistance training vs control, progressive resistance training vs aerobic training, and combined training vs aerobic training. From 268,778 titles, 34 studies were included (1940 participants; 71.9% male; age 60 ± 7 years). Progressive resistance training was more effective than control for lower (standardized mean difference 0.57, 95% confidence interval (0.17-0.96)) and upper (1.43 (0.73-2.13)) body strength. Aerobic fitness improved similarly after progressive resistance training (16.9%) or aerobic training (21.0%); (standardized mean difference -0.13, 95% confidence interval (-0.35-0.08)). Combined training was more effective than aerobic training for aerobic fitness (0.21 (0.09-0.34), lower (0.62 (0.32-0.92)) and upper (0.51 (0.27-0.74)) body strength. Twenty studies reported adverse event information, with five reporting 64 cardiovascular complications, 63 during aerobic training. Conclusion Isolated progressive resistance training resulted in an increase in lower and upper body strength, and improved aerobic fitness to a similar degree as aerobic training in coronary heart disease cohorts. Importantly, when progressive resistance training was added to aerobic training, effects on both fitness and strength were enhanced compared to aerobic training alone. Reporting of adverse events was poor, and clinical gaps were identified for women, older adults, high intensity progressive resistance training and long-term outcomes, warranting future trials to confirm safety and effectiveness.


Mechanical behavior of coronary stents investigated through the finite element method.
Intravascular stents are small tube-like structures expanded into stenotic arteries to restore blood flow perfusion to the downstream tissues. The stent is mounted on a balloon catheter and delivered to the site of blockage. When the balloon is inflated, the stent expands and is pressed against the inner wall of the coronary artery. After the balloon is deflated and removed, the stent remains in place, keeping the artery open. Hence, the stent expansion defines the effectiveness of the surgical procedure: it depends on the stent geometry, it includes large displacements and deformations and material non-linearity. In this paper, the finite element method is applied (i) to understand the effects of different geometrical parameters (thickness, metal-to-artery surface ratio, longitudinal and radial cut lengths) of a typical diamond-shaped coronary stent on the device mechanical performance, (ii) to compare the response of different actual stent models when loaded by internal pressure and (iii) to collect suggestions for optimizing the device shape and performance. The stent expansion and partial recoil under balloon inflation and deflation were simulated. Results showed the influence of the geometry on the stent behavior: a stent with a low metal-to-artery surface ratio has a higher radial and longitudinal recoil, but a lower dogboning. The thickness influences the stent performance in terms of foreshortening, longitudinal recoil and dogboning. In conclusion, a finite element analysis similar to the one herewith proposed could help in designing new stents or analyzing actual stents to ensure ideal expansion and structural integrity, substituting in vitro experiments often difficult and unpractical.


Acute meningoencephalitis after withdrawal of antibiotics in Whipple's disease.
A man with Whipple's disease was treated with oral penicillin (500 mg twice a day) for 2 years with eradication of bacillary organisms from the jejunum and a return of jejunal histologic findings to normal. While he was on this regimen, however, intermittent vertigo and tinnitus and decreased auditory acuity developed. Two days after penicillin was withdrawn, the patient developed acute meningoencephalitis that responded to parenteral penicillin and chloramphenicol therapy. Subsequently, central nervous system signs and symptoms and cerebrospinal fluid pleocytosis have been controlled with chronic chloramphenicol therapy. Penicillin may suppress, but not prevent, central nervous system disease in patients with otherwise successfully treated Whipple's disease.


Isolation and characterization of a bovine visceral endoderm cell line derived from a parthenogenetic blastocyst.
A cell line, BPE-1, was derived from a parthenogenetic 8-d in vitro-produced bovine blastocyst that produced a cell outgrowth on STO feeder cells. The BPE-1 cells resembled visceral endoderm previously cultured from blastocysts produced by in vitro fertilization (IVF). Analysis of the BPE-1 cells demonstrated that they produced serum proteins and were negative for interferon-tau production (a marker of trophectoderm). Transmission electron microscopy revealed that the cells were a polarized epithelium connected by complex junctions resembling tight junctions in conjunction with desmosomes. Rough endoplasmic reticulum was prominent within the cells as were lipid vacuoles. Immunocytochemistry indicated the BPE-1 cells had robust microtubule networks. These cells have been grown for over 2 yr for multiple passages at 1:10 or 1:20 split ratios on STO feeder cells. The BPE-1 cell line presumably arose from embryonic cells that became diploid soon after parthenogenetic activation and development of the early embryo. However, metaphase spreads prepared at passage 41 indicated that the cell population had a hypodiploid (2n = 60) unimodal chromosome content with a mode of 53 and a median and mean of 52. The cell line will be of interest for functional comparisons with bovine endoderm cell lines derived from IVF and nuclear transfer embryos.


Candida albicans protein analysis during hyphal differentiation using an integrative HA-tagging method.
In order to understand the biological complexity inherent to the pathogenicity of Candida albicans, gene expressions need to be analyzed at the protein level. We employed an epitope-tagging technique in a set of C. albicans ORF, and constructed fifteen strains which expressed HA-tagged proteins. These efforts permitted us to identify differentially synthesized proteins during the hyphal differentiations. ICL1, MLS1, and WAP1, all of which are known to be hypha-induced at the transcript level, were indeed found to be up-regulated at the protein level. We also identified CaeIF4G, CaTPO5, and CaZRT1, the protein levels of which were increased during hyphal transition, and CaERB1, the protein level of which was reduced consistently. The hypha-induced protein level of CaeIF4G was closely associated with the cellular hyphal phenotype. CaeIF4G overexpression was shown to result in hyperfilamentation in C. albicans. CaeIF4E, which was constitutively expressed during the hyphal development, exhibited no overexpression phenotype. HA-tagged strains were also utilized in our analysis of C. albicans proteins in a co-culture of macrophage and C. albicans. Five genes were found to be expressed differentially during the macrophage co-cultures. Our approaches proved to be rather useful under yeast culture conditions as well as in co-cultures of macrophage and C. albicans.


Phase II study of gemcitabine (2',2'-difluorodeoxycytidine) in previously treated ovarian cancer patients.
Platinum-containing combination chemotherapy has resulted in improved survival rates in patients with advanced ovarian carcinoma, but the majority of the patients still die of their disease. It is therefore important to develop new non-cross-resistant drugs. Gemcitabine (2',2'-difluorodeoxycytidine) has shown a broad spectrum of antineoplastic activity in tumor cell cultures in vitro and in animal tumor models. Clinical activity also has been reported in a variety of solid tumor types. Our purpose was to assess the clinical activity of gemcitabine in previously treated ovarian cancer patients and to further characterize the toxicity of the compound. Gemcitabine (800 mg/m2) was given intravenously once a week for 3 consecutive weeks, followed by 1 week of rest. A maximum of two different prior treatment regimens was allowed. Response was assessed by pelvic examination and/or ultrasound and computed tomography scans every other course. Fifty patients were eligible; 35 (70%) had bulky disease (tumor greater than 5 cm in diameter). All patients had received prior platinum-containing combination chemotherapy. Forty-two patients were assessable for response. Eight (19%) of the 42 patients (95% confidence interval = 9%-34%) achieved a partial response, with a median response duration of 8.1 months (range, 4.4-12.5 months). All responders started treatment with gemcitabine within 6 months of prior treatment, and seven of the eight responders were resistant to first-line platinum-containing combination chemotherapy. Overall median time to progression was 2.8 months (range, 0.2 12.5 months), and overall median survival was 6.2 months (range, 0.2-26.0 months). Forty-eight patients were assessable for toxicity. Leukocytopenia and thrombocytopenia were the main toxic effects that caused dose omissions (27% and 14%, respectively) and dose reductions (37% and 21%, respectively). A transient mild flu-like syndrome occurred in 28% of the patients, and treatment-related peripheral edema developed in 22%. Grade 1 hematuria (53% of patients), grade 1-2 proteinuria (79% of patients), and liver toxicity that was mostly grade 1-2 (59% of patients) were also observed. Gemcitabine is a well-tolerated new drug with activity in platinum-resistant ovarian cancer patients. Confirmatory trials are needed, and the activity of gemcitabine in previously untreated patients should be assessed.


Effect of electrical stimulation of the hippocampus upon corticosteroid levels in the freely-behaving, non-stressed rat.
The influence of the hippocampus upon pituitary release of adrenocorticotropic hormone (ACTH) was studied in male Sprague-Dawley rats which had concentric bipolar stainless stell electrodes chemically implanted in the dorsal and ventral hippocampus. Blood samples were withdrawn at half-hour intervals from a cannula in the right atrium. Plasma corticosterone levels reflected ACTH release. 30 min of 25 or 250-cps electrical stimulation of the hippocampus in the freely-behaving, non-stressed rat resulted in significant increases in basal plasma corticosterone levels evident at the end of stimulation. In afternoon experiments, after stimulation at either hippocampal site with 25 cps only, the increase was followed by a delayed inhibitroy phase and temporary inhibition of the circadian rise in corticosterone levels. The inhibitory effect was more pronounced with ventral than with dorsal hippocampal stimulation. The basis for these differential effects is discussed in terms of the anatomical organization of the hippocampus.


Seeing old friends from a different angle: novel properties of hematopoietic growth factors in the healthy and diseased brain.
Hematopoietic growth factors are known for their bolstering effects on the growth, survival, and differentiation of blood progenitor cells. Several of these cytokines also influence the proliferation of neural stem/progenitor cells, paralleling cellular mechanisms in analogy to their function in the hematopoietic system. Erythropoietin (EPO), granulocyte-colony stimulating factor (G-CSF), thrombopoietin (TPO), and their respective receptors are all expressed in the hippocampus of the mammalian brain. Recent studies have confirmed EPO and G-CSF as vital neurotrophic and neuroprotective factors, and ascertained their role in neuroprotection and neuroregeneration as pertaining to the most prominent neurodegenerative diseases. The aims of this review are to discuss newly discovered properties of G-CSF, EPO, and TPO beyond their known functions in the hematopoietic system, to create an overview of the accumulating data on the role of these factors in hippocampal function, and to highlight any potential clinical implications.


Urea excretion, galactose elimination, and aminopyrine disappearance during normal liver regeneration after partial hepatectomy. Comparison with other function tests reported.
After removal of 70% of normal rat liver, liver weight was 37% of control at 3 1/2 hours and 49% at 24 hours. Urea formation per gram liver after an NH4+ load and galactose elimination per gram liver were well-preserved during this early posthepatectomy period. At 46 hours after removal, galactose elimination was transiently less than would be expected from liver weight. The aminopyrine disappearance rate fell to 50% to 63% of control values until 72 hours, when it decreased further to 43%, disproportionately less than liver weight. The disappearance rate per gram liver at this time was 63% of control. Serum bile acid concentration increased 17-fold by 24 hours, and was five times that of control concentration at 72 hours. Comparisons of these four measures and six other in vivo measures of function previously reported permitted a segregation of the livers into two groups according to liver function after hepatectomy: those that were disproportionately preserved or were proportional to the amount of liver present, and those that were disproportionately reduced in relation to liver weight. Four additional measurements reported in isolated perfused livers after hepatectomy were similarly segregated. It appears that those liver functions that most closely reflect cellular growth or associated changes in liver blood flow are preserved, whereas those that are possibly more specialized and differentiated are depressed during regeneration.


Life after Stroke in an Urban Minority Population: A Photovoice Project.
Stroke is a leading cause of disability in the United States and disproportionately affects minority populations. We sought to explore the quality of life in urban, minority stroke survivors through their own photos and narratives. Using the Photovoice method, seventeen stroke survivors were instructed to take pictures reflecting their experience living with and recovering from stroke. Key photographs were discussed in detail; participants brainstormed ways to improve their lives and presented their work in clinical and community sites. Group discussions were recorded, transcribed, and coded transcripts were reviewed with written narratives to identify themes. Participants conveyed recovery from stroke in three stages: learning to navigate the initial physical and emotional impact of the stroke; coping with newfound physical and emotional barriers; and long-term adaptation to physical impairment and/or chronic disease. Participants navigated this stage-based model to varying degrees of success and identified barriers and facilitators to this process. Barriers included limited access for disabled and limited healthy food choices unique to the urban setting; facilitators included presence of social support and community engagement. Using Photovoice, diverse stroke survivors were able to identify common challenges in adapting to life after stroke and important factors for recovery of quality of life.


Opioid Rotation in Cancer Pain Treatment.
Rotating several different WHO level III opioid drugs is a therapeutic option for patients with chronic cancer-related pain who suffer from inadequate analgesia and/or intolerable side effects. The evidence favoring opioid rotation is controversial, and the current guidelines in Germany and other countries contain only weak recommendations for it. This review is based on pertinent publications retrieved by a systematic review of the literature on opioid rotation for adult patients with chronic cancerrelated pain who are regularly taking WHO level III opioids by the oral or trans - dermal route. 9 individual studies involving a total of 725 patients were included in the analysis, and 3 previous systematic reviews of studies involving a total of 2296 patients were also analyzed. Morphine, oxycodone, fentanyl, hydromorphone, and buprenorphine were used as first-line opioid drugs, and hydromorphone, bupre - norphine, tapentadol, fentanyl, morphine, oxymorphone, and methadone were used as second-line opioid drugs. In all of the studies, pain control was achieved for 14 days after each rotation. In most of them, the dose of the new drug introduced in each rotation needed to be increased above the dose initially calculated from a rotation ratio, with the exception of rotations to methadone. The frequency of side effects was only rarely lessened, but patients largely considered the result of opioid rotation to be positive. No particular opioid drug was found to be best. Opioid rotation can improve analgesia and patient satisfaction. The success of opioid rotation appears to depend on the magnitude of the initial dose, among other factors. Tables of equianalgesic doses should be considered no more than a rough guide for determining the dose of the new drug. Rotations to methadone should be carried out under clinical supervision in experienced hands.


Rocky Mountain ecosystems: diversity, complexity and interactions.
The interior west of North America provides many opportunities to study ecosystem responses to climate change, biological diversity and management of disturbance regimes. These ecosystem responses are not unique to the Rocky Mountains, but they epitomize similar scientific problems throughout North America. Better management of these ecosystems depends on a thorough understanding of the underlying biology and ecological interactions of the species that occupy the diverse habitats of this region. This review highlights progress in research to understand aspects of this complex ecosystem.


A Bemisia tabaci midgut protein interacts with begomoviruses and plays a role in virus transmission.
Begomoviruses are a major group of plant viruses, transmitted exclusively by Bemisia tabaci (Gennadius) in a persistent circulative non-propagative manner. The information regarding molecular and cellular basis underlying Begomovirus - whitefly interaction is very scarce. Evidences have suggested that the insect gut possesses some crucial protein receptors that allow specific entry of virus into the insect haemolymph. We have performed yeast two hybrid gut cDNA expression library screening against coat protein of Tomato leaf curl New Delhi virus (ToLCV) and Cotton leaf curl Rajasthan virus (CLCuV) as bait. Midgut protein (MGP) was the common protein found interacting with both ToLCV and CLCuV. MGP was localized in whole mount B. tabaci as well as in dissected guts through confocal microscopy. Pull down and dot blot assays confirmed in vitro interaction between ToLCV/CLCuV coat protein and MGP. Immunolocalization analysis also showed colocalization of ToLCV/CLCuV particles and MGP within insect's gut. Finally, anti-MGP antibody fed B. tabaci, exhibited 70% reduction in ToLCV transmission, suggesting a supportive role for MGP in virus transmission.


New species of Mutillid Mimicking Enoclerus Gahan (Coleoptera: Cleridae: Clerinae) from Mexico and Central America.
Six new species of Enoclerus are described: E. delusus n. sp. from Costa Rica and Panamá, E. incanus n. sp. from México, E. zip n. sp. from México and El Salvador, E. reductesignatus n. sp. from Panamá, and E. citrinifrons n. sp. and E. philogenes n. sp. from Costa Rica. The new species are hypothesized to participate in a Batesian mimicry complex with boldly marked diurnal mutillid wasps as their model. Enoclerus crabronarius var. deletus Wolcott is elevated to species rank as E. deletus Wolcott new status. The identity of E. crabronarius is discussed.


Acetal-linked polymeric prodrug micelles based on aliphatic polycarbonates for paclitaxel delivery: preparation, characterization, in vitro release and anti-proliferation effects.
Acidic tumor microenvironment has been extensively explored to design pH-responsive paclitaxel prodrug micelles for cancer therapy. The object of this study is to investigate the pH-responsive drug release behavior and the anti-proliferation capacity of acetal-linked paclitaxel polymeric prodrug micelles. The prodrug was synthesized and evaluated for paclitaxel content. The prodrug micelles were fabricated and characterized for morphology, size, in vitro pH-responsive paclitaxel release, cellular uptake, and anti-proliferation. Paclitaxel content was 33 wt%. The prodrug micelles exhibited spherical structure with the hydrodynamic diameter of 154 nm. Besides, the in vitro paclitaxel release behavior was verified to be pH-responsive, and 77%, 38%, and 17% of parent free paclitaxel was released from the nano-sized prodrug micelles in 13 h at pH 5.5, 6.5, and 7.4, respectively. The cellular uptake assessment demonstrated the time-dependent internalization of prodrug micelles. Meanwhile, CCK-8 analysis showed that prodrug micelles possessed the potent anti-proliferation effects. Prodrug micelles based on aliphatic polycarbonates present a promising platform for cancer chemotherapy due to the pH-responsive characteristics of acetal bond, potent anti-proliferation effects, and outstanding cytocompatibility of aliphatic polycarbonates.


The influence of verbal encouragement during assessment of maximal oxygen uptake.
This study examined the influence of verbal encouragement on the attainment of maximal oxygen consumption (VO2max) for competitive runners (n = 14) and untrained non-athletes (n = 14). Two maximal treadmill tests were performed with verbal encouragement or no encouragement. VO2max, respiratory exchange ratio (RER), heart rate, and blood lactate concentration were determined. Encouragement resulted in significantly (p < 0.05) higher values for VO2max (44.9v42.8 ml/kg.min-1), treadmill run time (14.3v12.4 mins), RER (1.10 +/- 0.98), maximal heart rate (196.0v192.7 bpm) and blood lactate (110.5v93.7 mg/dl) for the untrained subjects. VO2max, RER and maximal lactate values were not affected by verbal encouragement for the competitive runners, however, treadmill run times and maximal heart rate were significantly higher with encouragement. These results suggest that attainment of VO2max is not dependent on external encouragement for highly trained competitive runners. However, encouragement may be necessary to assure attainment of VO2max for untrained non-athletes.


Mucoepidermoid carcinoma of the bronchus: a review.
Although mucoepidermoid carcinoma of the salivary gland is relatively common, mucoepidermoid carcinoma arising from the mucous glands of the bronchus is rare. Bronchial mucoepidermoid carcinoma usually presents as an intraluminal mass producing luminal occlusion. Symptoms are airway obstruction and recurrent pneumonia. Macroscopically, mucoepidermoid carcinoma appears as an exophytic intrabronchial mass with intact or ulcerated bronchial mucosa. Microscopically, the tumors are located in the submucosa of the large bronchi. The tumors are usually well differentiated and contain a combination of mucus-secreting, squamous, and intermediate cells. The increased frequency of this tumor in the pediatric population suggests a genetic abnormality. Recent genetic studies have demonstrated reciprocal chromosomal translocations including t(1;11)(p22;q13), t(11;19)(q14-21;p12), and t(11; 19)(q21;p13). Chromosome 11 in the first translocation appears to have been altered resulting in up-regulation of the cyclin D1 gene and overexpression of cyclin D1. The t(11;19)(q21;p13) encodes a novel fusion product capable of disrupting the Notch signaling pathway.


Polyamines modulate the subcellular localization of RNA-binding protein HuR through AMP-activated protein kinase-regulated phosphorylation and acetylation of importin alpha1.
Polyamines are required for maintenance of intestinal epithelial integrity, and a decrease in cellular polyamines increases the cytoplasmic levels of RNA-binding protein HuR stabilizing p53 and nucleophosmin mRNAs, thus inhibiting IEC (intestinal epithelial cell) proliferation. The AMPK (AMP-activated protein kinase), an enzyme involved in responding to metabolic stress, was recently found to be implicated in regulating the nuclear import of HuR. Here, we provide evidence showing that polyamines modulate subcellular localization of HuR through AMPK-regulated phosphorylation and acetylation of Impalpha1 (importin alpha1) in IECs. Decreased levels of cellular polyamines as a result of inhibiting ODC (ornithine decarboxylase) with DFMO (D,L-alpha-difluoromethylornithine) repressed AMPK activity and reduced Impalpha1 levels, whereas increased levels of polyamines as a result of ODC overexpression induced both AMPK and Impalpha1 levels. AMPK activation by overexpression of the AMPK gene increased Impalpha1 but reduced the cytoplasmic levels of HuR in control and polyamine-deficient cells. IECs overexpressing wild-type Impalpha1 exhibited a decrease in cytoplasmic HuR abundance, while cells overexpressing Impalpha1 proteins bearing K22R (lacking acetylation site), S105A (lacking phosphorylation site) or K22R/S105A (lacking both sites) mutations displayed increased levels of cytoplasmic HuR. Ectopic expression of these Impalpha1 mutants also prevented the increased levels of cytoplasmic HuR following polyamine depletion. These results indicate that polyamine-mediated AMPK activation triggers HuR nuclear import through phosphorylation and acetylation of Impalpha1 in IECs and that polyamine depletion increases cytoplasmic levels of HuR as a result of inactivation of the AMPK-driven Impalpha1 pathway.


The nature of time: implications for research on aging.
Contemporary research on aging gives little evidence of recognition of the underlying concepts of time. Researchers have been much concerned with age as a variable but little with the explication of aging as a process. Most authors do not define aging as they use the term or explain how time enters their causal explanations. In this article major concepts of time are reviewed and distinctions are made between physical, biological, psychological, and social time or age, which all might be classified as a variant of calendar time or calendar age, respectively. Recent developments in gerodynamics, however, have given rise to the concepts of intrinsic time and intrinsic age, which are generated by the dynamics of the system. The implications of the major concepts of time and age will be drawn for research on aging.


The Swedish Heart Failure Registry: a living, ongoing quality assurance and research in heart failure.
Heart failure (HF) represents a global pandemic. Although in HF with reduced ejection fraction (HFrEF) randomized controlled trials have provided effective treatments, prognosis still remains poor, with signals of undertreatment. HF with mid-range EF (HFmrEF) has no evidence-based therapy, and its characterization is ongoing. Trials in HF with preserved EF (HFpEF) have failed to provide any effective treatment, but there are several concerns about their design. Thus, current challenges in the HF field are: 1) optimizing the use of existing treatments in HFrEF; 2) developing and proving efficacy of new treatments, and of new use of existing treatments in HFpEF and HFmrEF. Here we describe how registry-based research can improve knowledge addressing the unmet needs in HF, and in particular we focus on the contribution of the Swedish Heart Failure Registry to this field.


Purification of Pharmaceutical Solvents by Pervaporation through Hybrid Silica Membranes.
Solvents purification mainly used in pharmaceutical field such as acetone and methyl ethyl ketone (MEK) were performed through hybrid silica membranes and from binary and multi-components mixtures. Two hybrid silica membranes-zirconia doped bis(triethoxysilyl)methane and bis(triethoxysilyl)ethane (BTESE)-were studied. Flux, permeance, and separation factor were evaluated depending on temperature, composition, and number of organic compounds in the feed. Dehydration tests of acetone were operated at 30 and 45 °C following by acetone and MEK purification at 50 °C from multi-components hydro-organic mixtures where hydrophilic compounds (water, methanol) but also hydrophobic (dichloromethane (DCM) and/or toluene) were present. Results showed that the presence of Zr nanoparticles affected flux and improved selectivity in the case of dehydration. Experiments related to acetone and MEK purification, revealed a mass transfer alteration and a decrease of performance, from 99 to 97 wt% and from 98 to 95 wt% respectively, when the number of compounds in the initial feed grown up and more precisely, in the presence of DCM and toluene thus highlighting a possible coupling effect.


Percutaneous intravertebral body embolization of a traumatic spinal epidural arteriovenous fistula with secondary perimedullary venous reflux. A case report.
Arteriovenous fistulas following vertebral fractures are probably very rare. We present a case with fistulous connection between arteries and veins within the fractured 12th thoracic vertebral body with retrograde venous drainage to perimedullary veins resulting in spinal venous hypertension and a cauda equina like symptomatology. Pre-treatment 3D CT enabled us to puncture the venous pouch within the vertebra and deposit glue in the vertebral fistula. The procedure led to a complete occlusion of the fistula and relief of pain and neurological symptoms.


Synthesis of few-layer GaSe nanosheets for high performance photodetectors.
Two-dimensional (2D) semiconductor nanomaterials hold great promises for future electronics and optics. In this paper, a 2D nanosheets of ultrathin GaSe has been prepared by using mechanical cleavage and solvent exfoliation method. Single- and few-layer GaSe nanosheets are exfoliated on an SiO(2)/Si substrate and characterized by atomic force microscopy and Raman spectroscopy. Ultrathin GaSe-based photodetector shows a fast response of 0.02 s, high responsivity of 2.8 AW(-1) and high external quantum efficiency of 1367% at 254 nm, indicating that the two-dimensional nanostructure of GaSe is a new promising material for high performance photodetectors.


Taxonomic changes in the genus Diabrotica Chevrolat (Coleoptera: Chrysomelidae: Galerucinae): results of a synopsis of North and Central America Diabrotica species.
The following new synonyms in Diabrotica Chevrolat 1836 are proposed: D.flaviventris Jacoby 1887 and D. tibialis Jacoby 1887 are synonyms of D. adelpha Harold 1875; D. peckii Bowditch 1911 is a synonym of D. bioculata Bowditch 1911; D. nummularis Harold 1877 is a synonym of D. circulata Harold 1875; D. linensis Bechyné 1956 is a synonym of D. trifurcata Jacoby 1887; D. brunneosignata Jacoby 1887 is a synonym of D. sinuata Olivier 1790; D. duplicata Jacoby 1887 is a synonym of D. viridifasciata Jacoby 1887. Diabrotica cyaneomaculata Jacoby 1887 does not share the synapomorphies of Diabrotica and is treated as incertae sedis. Diabrotica tripunctata (Fabricius) is removed from synonymy with D. sinuata Olivier and is considered to be a valid species. The original combination is restored for Diabroticafasciata Kirsch, the species being transferred from Paranapiacaba Bechyné back to Diabrotica. It was found that the type series of D. godmani Jacoby contains seven different taxa: one is D. godmani itself; one is D. championi Jacoby; one is D. quadricollis Jacoby; three are unidentified Diabrotica species, each different from the others; and one is not a Diabrotica. The type series of D. viridicollis Jacoby contains four different taxa, D. viridicollis Jacoby itself and three different unidentified Diabrotica species.


[Quantification of sebaceous excretion in volunteers: influence of chronological age, sex and race].
The "sebum" secretion was evaluated in caucasian, black, yellow and mullato people of different ages by the osmic acid technique utilizing a semi-quantitative scale of score ranging from 0 to 9 points. The results have shown: 1) there is significant difference between to "sebum" secretion (CL = casual level or SER = sebum excretion rate) of males and females greater than or equal to 60 years old, regardless the race; 2) males and females of each age subgroup have shown no difference of "sebum" secretion (NC or TRE) regardless the race; 3) male volunteers of different races have shown no difference secretion regardless the age and the race. On the other hand, females greater than or equal to 60 years old, regardless the race have shown low "sebum" secretion tham of 15-19 and 50-59 years old; 4) no circadian, ultradian and seasonal rhythm of "sebum" secretion were verified.


Ectopic Cushing's syndrome caused by an esthesioneuroblastoma.
To report a case of florid Cushing's hormone (ACTH) secretion related to the presence of an esthesioneuroblastoma (ENB). We present clinical, laboratory, and pathologic findings in a 36-year-old Caucasian man presenting with Cushing's syndrome. Results of computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) scanning, and somatostatin receptor scintigraphy are presented, along with tumor pathology findings. After initial biochemical studies suggestive of ectopic Cushing's syndrome, CT of the chest and abdomen revealed multiple cavitated pulmonary lesions, an ischiorectal mass, and bilateral adrenal hyperplasia. MRI of the pituitary gland revealed normal findings. Both PET scanning with [18 F]-flurodeoxyglucose (FDG) and somatostatin receptor scintigraphy with 111 indium-penetetreotide (Octreoscan) revealed strong tracer uptake in the ethmoid region. CT and MRI of the sinuses and brain subsequently localized a 5-cm mass in the ethmoid sinuses with intracranial extension. On biopsy, pathology results were consistent with a diagnosis of ENB, and immunohistochemical analysis revealed that tumor cells were strongly positive for ACTH, synaptophysin, and S-100, providing definitive diagnosis of ACTH-producing ENB. Hypercortisolemia was initially controlled by metyrapone, then by external beam radiation therapy (RT). This case illustrates the usefulness of nuclear imaging in the diagnosis of ENB, and the importance of prompt control of hypercortisolemia in Cushing's syndrome.


Mortality in Miners with Coal-Workers' Pneumoconiosis in the Czech Republic in the Period 1992-2013.
While working underground, miners are exposed to a number of risk factors that have a negative impact on their health and may be a cause of an increased mortality in miners. The aim of the study was to compare total and specific mortality in black coal miners with acknowledged coal-workers' pneumoconiosis (CWP) and without CWP, and the mortality of the general male population in the Czech Republic in the period 1992-2013. The sample consisted of 3476 coal miners with CWP and 6687 ex-coal miners without CWP, who were removed after achieving the maximum permissible exposure (MPE). The mortality risk differences were analyzed with the use of the standardized mortality ratio (SMR) and 95% confidence interval. Significantly higher total mortality (SMR = 1.10; 95% CI: 1.02-1.17), and mortality from malignant neoplasm (SMR = 1.16; 95% CI: 1.03-1.30), lung cancers (SMR = 1.70; 95% CI: 1.41-2.04), and non-malignant respiratory diseases (SMR = 2.78; 95% CI: 2.32-3.31) were found in the sample of coal miners with CWP. In this sample, the severity of CWP was assessed, and the SMR increased with the severity of CWP. The total (SMR = 0.86; 95% CI: 0.82-0.91) and specific mortality of miners without CWP were not higher compared with the general population. In the case where the miners were removed from underground work after achieving the MPE (without CWP), their mortality was not higher than that of the general population, but the mortality of miners with CWP was higher compared to the general population. This mortality was affected by malignant and non-malignant respiratory diseases.


New Online Tool for Exploring Global Opioid Consumption Data.
Each year for nearly two decades, the Pain & Policy Studies Group (PPSG) has received from the International Narcotics Control Board, the global monitoring body for the implementation of the United Nations international drug control conventions, consumption data for six principal opioids used to treat moderate and severe pain: fentanyl, hydromorphone, methadone, morphine, oxycodone, and pethidine. To provide these statistics to a wider audience, PPSG developed an extensive section of its Web site featuring these data in the form of global, regional, and individual country graphs. In recent years, PPSG developed and launched three new interactive Web features for exploring opioid consumption data and generating hypotheses about patterns of opioid consumption. In July 2016, PPSG announced the addition of a new tool on its Web site to explore opioid consumption data: custom consumption graphs for opioid medicines. This tool allows users to select, customize, and create charts of the opioid consumption data and download them for use in presentations or publications. PPSG encourages colleagues to use these tools to explore and study these data to inform their work to improve the accessibility and availability of these important medicines.


Joint commissioning. Going halves.
Joint commissioning and provision of mental health services in Somerset failed to produce significant benefits to users over its first two years. Users considered access to services deteriorated and concerns remain that there is no alternative to hospital admission in crises. Users and carers were included as non-voting members of the commissioning board, but users felt less involved in care planning than previously. The combined health and social care trust does not seem to have delivered anything which has not been achieved elsewhere without the transfer of social care staff to a new employer.


Mechanisms behind the faceting of catanionic vesicles by polycations: chain crystallization and segregation.
Vesicles composed of an anionic and a cationic surfactant, with a net negative charge, associate strongly with a hydrophobically modified polycation (LM200) and with an unmodified polycation with higher charge density (JR400), forming viscoelastic gel-like structures. Calorimetric results show that in these gels, LM200 induces a rise of the chain melting temperature (Tm) of the vesicles, whereas JR400 has the opposite effect. For both polymer-vesicle systems, the shear viscosity exhibits an inflection point at Tm, and for the LM200 system the measured relaxation times are significantly higher below Tm. The neat vesicles and the polycation-bound vesicles have a polygonal-like faceted shape when the surfactant chains in the bilayer are crystallized, as probed by cryo-transmission electron microscopy. Above Tm, the neat and the LM200-bound vesicles regain a spheroidal shape, whereas those in the JR400 system remain with a deformed faceted shape even above Tm. These shape changes are interpreted in terms of different mechanisms for the polymer-vesicle interaction, which seem to be highly dependent on polymer architecture, namely charge density and hydrophobic modification. A crystallization-segregation mechanism is proposed for the LM200-vesicle system, while, for the JR400-vesicle one, charge polarization-lateral segregation effects induced by the polycation in the catanionic bilayer are envisaged.


Lipid Nanoparticle Encapsulation Empowers Poly(I:C) to Activate Cytoplasmic RLRs and Thereby Increases Its Adjuvanticity.
Poly(I:C) is a synthetic analogue of dsRNA capable of activating both TLR3 and RLRs, such as MDA-5 and RIG-I, as pathogen recognition receptors. While poly(I:C) is known to provoke a robust type I IFN, type III IFN, and Th1 cytokine response, its therapeutic use as a vaccine adjuvant is limited due to its vulnerability to nucleases and poor uptake by immune cells. is encapsulated poly(I:C) into lipid nanoparticles (LNPs) containing an ionizable cationic lipid that can electrostatically interact with poly(I:C). LNP-formulated poly(I:C) triggered both lysosomal TLR3 and cytoplasmic RLRs, in vitro and in vivo, whereas poly(I:C) in an unformulated soluble form only triggered endosomal-localized TLR3. Administration of LNP-formulated poly(I:C) in mouse models led to efficient translocation to lymphoid tissue and concurrent innate immune activation following intramuscular (IM) administration, resulting in a significant increase in innate immune activation compared to unformulated soluble poly(I:C). When used as an adjuvant for recombinant full-length SARS-CoV-2 spike protein, LNP-formulated poly(I:C) elicited potent anti-spike antibody titers, surpassing those of unformulated soluble poly(I:C) by orders of magnitude and offered complete protection against a SARS-CoV-2 viral challenge in vivo, and serum from these mice are capable of significantly reducing viral infection in vitro.


An ethics framework for organizational change.
The proliferation of managed care has introduced conflicts of interest in health care that can create tension in the traditional care provider-patient relationship. In order to address the emerging trends and potential ethical dilemmas presented by managed care, health systems must develop a framework for intentional ethical reflection. The article outlines the essential elements of a caring ethical framework and describes how one integrated health system created a framework of ethical guiding principles and an ethical organizational structure to facilitate integration of those principles throughout the organization.


Obstacles to organ donation.
Attitudes towards transplantation were investigated in national surveys of the general public (n = 1471), the medical profession (n = 590) and key clinical staff in units referring potential organ donors (n = 380). A clear majority of doctors would like to see more transplants. Only 16 per cent of doctors opposed them on cost grounds, and a 50 per cent 5-year survival rate is seen as more than adequate clinical justification. However, doctors are less supportive of liver and heart grafts than of kidney and cornea grafts. Few lay people would refuse donation of specific organs, but 30 per cent worry that doctors might be pressured into removal of organs when they are not sure the patient is dead. Religious or moral objection is rare. Intensive care unit staff felt the most important factor restricting organ harvest in their own units was dislike of adding to relatives' distress, followed by lack of training in approaching relatives and adverse media publicity. Only 11 per cent thought reservations on brain stem death a likely or possible influence. Enhanced public awareness of the need for transplants was seen as the most important means of increasing organ harvest. Required request would be controversial and perhaps impossible to implement. We conclude that the time, effort and expense involved in potential organ donation do not play a substantial part in limiting referral. Neither do reservations about brain stem death. Increased training of staff (both in communication skills and in the professional responsibility to encourage donation) and greater public awareness are seen as the twin foundations of a realistic approach to enhancing referral.


Femtosecond near-infrared laser microirradiation reveals a crucial role for PARP signaling on factor assemblies at DNA damage sites.
Laser microirradiation is a powerful tool for real-time single-cell analysis of the DNA damage response (DDR). It is often found, however, that factor recruitment or modification profiles vary depending on the laser system employed. This is likely due to an incomplete understanding of how laser conditions/dosages affect the amounts and types of damage and the DDR. We compared different irradiation conditions using a femtosecond near-infrared laser and found distinct damage site recruitment thresholds for 53BP1 and TRF2 correlating with the dose-dependent increase of strand breaks and damage complexity. Low input-power microirradiation that induces relatively simple strand breaks led to robust recruitment of 53BP1 but not TRF2. In contrast, increased strand breaks with complex damage including crosslinking and base damage generated by high input-power microirradiation resulted in TRF2 recruitment to damage sites with no 53BP1 clustering. We found that poly(ADP-ribose) polymerase (PARP) activation distinguishes between the two damage states and that PARP activation is essential for rapid TRF2 recruitment while suppressing 53BP1 accumulation at damage sites. Thus, our results reveal that careful titration of laser irradiation conditions allows induction of varying amounts and complexities of DNA damage that are gauged by differential PARP activation regulating protein assembly at the damage site.


Benthic hydroids (Cnidaria: Hydrozoa) from off George V Coast (East Antarctica).
Hydrozoans are one of the main and most characteristic zoological groups of Antarctic benthic communities, yet there are Antarctic areas where the hydrozoan fauna is completely unknown or scarcely known as off George V Coast (East Antarctica). Hitherto, only two studies have dealt with hydroids from this area and only 16 species have been reported. The present study contributes to increase knowledge of the benthic hydroid fauna off George V Coast by studying material collected during a sampling survey associated with the CEAMARC project. A total of 12 species of benthic hydroids were found. Anthoathecata is only represented by Bimeria corynopsis, the remaining species, including Schizotricha auroraaustralis sp. nov., belong to Leptothecata. Seven of the 12 species found in the study represent new records for the area; therefore, the number of benthic hydroids known off George V Coast is raised to 23. Staurotheca is the most speciose genus, represented by three species, followed by Schizotricha with two; the remaining genera are each represented by a single species. All species are restricted to Antarctic or Antarctic/sub-Antarctic waters. Nine species (75%) are endemic to the Antarctic region, most with a circum-Antarctic distribution (7 species); only two are endemic to East Antarctica. Three species are also distributed in sub-Antarctic waters.


Co-crystallisation and humanisation of an anti-HER2 single-domain antibody as a theranostic tool.
Human epidermal growth factor receptor-2 (HER2) is a well-recognised biomarker associated with 25% of breast cancers. In most cases, early detection and/or treatment correlates with an increased chance of survival. This study, has identified and characterised a highly specific anti-HER2 single-domain antibody (sdAb), NM-02, as a potential theranostic tool. Complete structural description by X-ray crystallography has revealed a non-overlapping epitope with current anti-HER2 antibodies. To reduce the immunogenicity risk, NM-02 underwent a humanisation process and retained wild type-like binding properties. To further de-risk the progression towards chemistry, manufacturing and control (CMC) we performed full developability profiling revealing favourable thermal and physical biochemical 'drug-like' properties. Finally, the application of the lead humanised NM-02 candidate (variant K) for HER2-specific imaging purposes was demonstrated using breast cancer HER2+/BT474 xenograft mice.


Net-Clipping: An Approach to Deduce the Topology of Metal-Organic Frameworks Built with Zigzag Ligands.
Herein we propose a new approach for deducing the topology of metal-organic frameworks (MOFs) assembled from organic ligands of low symmetry, which we call net-clipping. It is based on the construction of nets by rational deconstruction of edge-transitive nets comprising higher-connected molecular building blocks (MBBs). We have applied net-clipping to predict the topologies of MOFs containing zigzag ligands. To this end, we derived 2-connected (2-c) zigzag ligands from 4-c square-like MBBs by first splitting the 4-c nodes into two 3-c nodes and then clipping their two diagonally connecting groups. We demonstrate that, when this approach is applied to the 17 edge-transitive nets containing square-like 4-c MBBs, net-clipping leads to generation of 10 nets with different underlying topologies. Moreover, we report that literature and experimental research corroborate successful implementation of our approach. As proof-of-concept, we employed net-clipping to form three new MOFs built with zigzag ligands, each of which exhibits the deduced topology.


[A case of hypospadias in a woman whose incontinence was repaired surgically].
On August 23, 1982 a 24-year-old woman presented with incontinence following her first delivery. From infancy she used to void urine frequently. When she was 4 years old a left nonfunctioning kidney was diagnosed and left nephrectomy was done. The external genitalia were remarkable in that there was a solitary orifice in the vestibule. The other items in the examination were normal. Vaginal examination revealed that the urethral meatus was on the anterior vaginal wall about 3 cm proximal to its orifice. Bladder neck and proximal urethral narrowing combined with suspension of bladder neck was performed on January 19, 1983. Postoperative course was uneventful and she was continent when the bladder was filled up to 200 ml while she stood erect. Our case might belong to group 3 according to Blum 's classification.


Measurement-based care training curriculum in psychiatry residency programs: I: Description of the curriculum and demonstration of implementation.
Recent literature shows that most practicing psychiatrists do not receive training in measurement-based care (MBC). Among the primary barriers to MBC implementation are the lack of formal training and curriculums. We present the first comprehensive MBC curriculum for use in adult psychiatric practice, and describe how the curriculum is adapted and implemented in psychiatry residency training programs. The Standard for Clinicians' Interview in Psychiatry (SCIP) was developed as a measurement-based care tool for clinicians' use. The SCIP is the only instrument that includes 18 reliable and validated clinician-rated scales covering most adult psychiatric disorders. The SCIP has simple, unified rules of measurement that apply to the 18 scales. The MBC curriculum includes 2 instruction manuals, 4 didactic lectures, and 12 videotaped interviews. We describe the annual learning and implementation of MBC curriculum in residency programs. The curriculum implementation at West Virginia University and Delaware Psychiatric Center began in 2019 and is ongoing. We present 3 case demonstrations of the implementation of MBC in clinical settings. Comprehensive implementation of MBC curriculum in residency programs has the potential to facilitate research and create a "culture" of MBC in future generations of psychiatrists.


[Amphiphilic drugs. 2. Relation between colloidal properties and pharmaceutic-technological, pharmacokinetic and pharmacodynamic behavior].
The physicochemical properties of amphiphilic drugs may affect the technological, pharmacokinetic and pharmacodynamic behaviours. Micelle formation of a drug is of considerable importance for its solubility, stability, adsorption pattern, mixed micelle formation and influences thus its pharmaceutical availability. The biological availability is in many cases decreased by interactions of a surface active drug with other substances before absorption, by altered diffusion behaviour and distribution properties. Colloidal association may also result in an alteration of pharmacodynamic effects. These relations depend on the fact, that discrete hydrophobic an hydrophilic parts in a molecule are also prerequisites for micelle formation and receptor interactions. Furthermore the high membrane affinity of these drugs is responsible for some therapeutic and toxic effects.


Ovalbumin coupled either with murine red blood cells or liposome induces IgG but not IgE antibody production.
Ovalbumin (OVA) was coupled with murine red blood cells (MRBC) using glutaraldehyde. The OVA-MRBC conjugate induced anti-OVA IgG antibody in mice at almost the same level as OVA in alum. However, no IgE antibody production specific for OVA was observed in OVA-MRBC-injected mice. A significant increase in IGG2a production was obtained with OVA-MRBC immunization, whereas the production of IgG1 predominated in OVA in alum immunization. Am OVA-liposome conjugate induced IgE-specific unresponsiveness in mice in the same manner as OVA-MRBC. Similar results were obtained when antigens other than OVA, such as tetanus toxoid or diphtheria toxoid, were coupled to liposome. These results show the potential of antigen-liposome conjugates for the development of vaccine that induces sufficient IgG antibody production without IgE synthesis.


Language and task effects on lateralized word recognition.
Behavioral laterality effects in naming and lexical decision in Farsi and English were used to evaluate three theories of cross-linguistic differences. First, the Scanning hypothesis predicts a smaller right visual hemifield advantage (RVFA) in Farsi in both tasks. Second, the Cerebral Dominance hypothesis predicts a consistent RVFA in both languages. Third, the Right Hemisphere hypothesis predicts a selective decrease in RVFA in Farsi for those components of the task that involve lexical semantic access. Results supported the Right Hemisphere hypothesis, showing greater right hemisphere contribution to orthographic addressing in Farsi than in English.


Daily Posture Behavior Patterns Derived From Multitime-Scale Topic Models Using Wearable Triaxial Acceleration for Assessment of Concern About Falling.
Concern about falling is prevalent in older population. This condition would cause a series of adverse physical and psychological consequences for older adults' health. Traditional assessment of concern about falling is relied on self-reported questionnaires and thus is too subjective. Therefore, we proposed a novel multi-time-scale topic modelling approach to quantitatively evaluate concern about falling by analyzing triaxial acceleration signals collected from a wearable pendent sensor. Different posture segments were firstly recognized to extract their corresponding feature subsets. Then, each selected feature related to concern about falling was clustered into discrete levels as feature letters of artificial words in different time scales. As a result, all older participants' signal recordings were converted to a collection of artificial documents, which can be processed by natural language processing methodologies. The topic modelling technique was used to discover daily posture behavior patterns from these documents as discriminants between older adults with different levels of concern about falling. The results indicated that there were significant differences in distributions of posture topics between groups of older adults with different levels of concern about falling. Additionally, the transitions of posture topics over daytime and nighttime revealed temporal regularities of posture behavior patterns of older adult's active and inactive status, which were substantially different for older adults with different levels of concern about falling. Finally, the level of concern about falling was accurately determined with accuracy of 71.2% based on the distributions of posture topics combined with the mobility performance metrics of walking behaviors and demographic information.


[Laparoscopic uretero-ureterostomy for iatrogenic lesions of the distal uréter.]
The most frequent ureteral lesions are iatrogenic, mainly due to gynecologic and urologic procedures. The resolution and repair of these lesions, when they require surgery, is often the performance of ureteroneocystostomy. We describe the technique for the repair of distal ureter lesions that preserves both anatomy and function of the urinary tract (1). The operation consists in dissection and extraction of the distal ureteral stump from its intramural tract to get at least 1 cm of free ureter, percutaneous insertion of a ureteral stent, checking the absence of tension between proximal ureter and distal dissected stump, end to end anastomosis and reinsertion of the distal ureter in the previously dissected bladder muscle layer. We present 4 cases of ureteral injury after laparoscopic simple total hysterectomy for uterine myomas with complete section of the distal ureter, that were operated 3-5 days after injury, performing laparoscopic repair surgery. We performed clinical and radiological control with intravenous urography demonstrating ureteral continuity normalization and good renal function. We believe that repair of the urinary tract with anatomical and physiological preservation must be the first option in the laparoscopic treatment of complete distal ureteral injuries, and intramural ureter dissection when needed avoids the performance of ureteroneocystostomy. It is necessary to keep progressing in the technique improvement, and to increase the number of cases and experience.


The smoking behaviors of incarcerated smokers.
To determine smoking behaviors, quit attempts, and cessation preferences among incarcerated smokers, a cross-sectional survey was given to a sample of inmates from three state prison facilities in the United States. A majority of Black smokers (62%) identified as smokers, and 38% identified as ex-smokers, as compared to 46.4 percent of smokers (and 53.6% of ex-smokers) in the non-Black group. There were significant differences in the number of cigarettes smoked per day with non-Black smokers smoking one pack (M = 20.44, standard deviation = 15.86) than Black smokers (M = 14.49, standard deviation = 13.43; t = -2.50, p = 0.014). Smoking cessation interventions are needed to reduce smoking during incarceration.