Trabecular bone adapts to long-term cyclic loading by increasing stiffness and normalization of dynamic morphometric rates.
Bone has the ability to adapt to external loading conditions. Especially the beneficial effect of short-term cyclic loading has been investigated in a number of in vivo animal studies. The aim of this study was to assess the long-term effect (>10 weeks) of cyclic mechanical loading on the bone microstructure, bone stiffness, and bone remodeling rates. Mice were subjected to cyclic mechanical loading at the sixth caudal vertebra with 8N or 0N (control) three times per week for a total period of 14 weeks. Structural bone parameters were determined from in vivo micro-computed tomography (micro-CT) scans performed at week 0, 4, 6, 8, 10, 12, and 14. Mechanical parameters were derived from micro-finite element analysis. Dynamic bone morphometry was calculated using registration of serial micro-CT scans. Bone volume fraction and trabecular thickness increased significantly more for the loaded group than for the control group (p = 0.006 and p = 0.002 respectively). The trabecular bone microstructure adapted to the load of 8N in approximately ten weeks, indicated by the trabecular bone volume fraction, which increased from 16.7% at 0 weeks to 21.6% at week 10 and only showed little change afterwards (bone volume fraction of 21.5% at 14 weeks). Similarly bone stiffness - (at the start of the experiment 649N/mm) - reached 846N/mm at 10 weeks in the loaded group and was maintained to the end of the experiment (850N/mm). At 4 weeks the bone formation rate was 32% greater and the bone resorption rate 22% less for 8N compared to 0N. This difference was significantly reduced as the bone adapted to 8N, with 8N remodeling rates returning to the values of the 0N group at approximately 10 weeks. Together these data suggest that once bone has adapted to a new loading state, the remodeling rates reduce gradually while maintaining bone volume fraction and stiffness.


Nurse-driven early rehabilitation protocol for critically ill children.
Physical impairment is a major morbidity in children surviving intensive care. The main objective of this study was to evaluate the effectiveness of a nurse-driven protocol in the early mobilization of critically ill children in terms of reduction of motor dysfunction, pediatric intensive care unit stays, and ventilator days. The secondary objective was to evaluate safety, in terms of injury, dislodgement of medical devices, and cardiorespiratory instability attributable to the intervention. The early rehabilitation intervention was initiated in July 2020. This retrospective interrupted time-series study was divided into the pre-implementation phase (January-June 2020) and the post-implementation phase (July-December 2020). The motor function domain of the Functional Status Scale was used to define the motor dysfunction after pediatric intensive care unit discharge. Twenty-five children were allocated in each group. The median age of the whole cohort was 11.5 months and approximately 58% of the population was male. The baseline characteristics of both groups were not statistically significant. There was a statistically significant reduction in motor dysfunction after protocol implementation (64.0% vs 36.0%; P = 0.044) with an absolute risk reduction of 28%. The number needed to treat was 3.6 children. There were no statistically significant differences in the median ventilator days, length of stay in the intensive care unit, and hospital length of stay. No complications were found. A nurse-driven protocol for the early mobilization of critically ill children was feasible and could be effective in reducing post-intensive care motor dysfunction.


Randomized clinical study of the efficacy of amiloride and potassium canrenoate in nonazotemic cirrhotic patients with ascites.
Although some clinical studies seem to prove the efficacy of nonantialdosteronic potassium-sparing diuretics in the treatment of ascites, no controlled study has compared the efficacy of these drugs with that of antialdosteronic diuretics. Forty nonazotemic cirrhotic patients were randomized to receive amiloride (group A, n = 20) or potassium canrenoate (group B, n = 20). The initial doses of amiloride and potassium canrenoate were 20 mg and 150 mg, respectively. The doses were increased in stepwise fashion to 60 and 500 mg/day, respectively, if no response ensued. Nonresponders to the highest doses of each drug were later treated with potassium canrenoate and amiloride, respectively. Seven of 20 group A patients responded to amiloride, whereas 14 of 20 group B patients responded to potassium canrenoate (p < 0.025). Seven of 13 nonresponders to amiloride later responded to potassium canrenoate, whereas only two of the nonresponders to potassium canrenoate later responded to amiloride. The diuretic responses to amiloride and potassium canrenoate were related to the activity of the renin-aldosterone system. All responders to amiloride (n = 9) had normal values of plasma aldosterone. All nonresponders to amiloride who later responded to potassium canrenoate (n = 7) had increased levels of plasma aldosterone. Moreover, on comparison of all responders (n = 21) and nonresponders (n = 12) to potassium canrenoate, a higher degree of renal proximal sodium reabsorption (with consequent limitation of sodium delivery to the distal tubule) was found to be the main difference.(ABSTRACT TRUNCATED AT 250 WORDS)


The effects of pentobarbitone, diazepam and alcohol on oral breathing in neonatal and mature sheep.
Our aim was to determine the effects of pharmacological sedation on oral breathing induced by nasal obstruction in chronically prepared newborn and mature sheep. Nasal obstruction (5 min) was achieved by blocking tubes temporarily fixed into the nostrils. We continuously recorded EMG activity of the diaphragm, genioglossus and digastric muscles, intrapleural pressure and percent O2 saturation in arterial blood (SaO2). Blood samples were taken intermittently and analysed for SaO2, P02, PCO2 and pH. As previously reported, nasal obstruction in lambs and ewes led to asphyxial changes in blood gases and pH; lambs were affected more than ewes. Respiratory responses to nasal obstruction were retested after administration of pentobarbitone Na (5 and 10 mg/kg), diazepam (0.2 and 0.4 mg/kg) and alcohol (nominally 0.075 and 0.11% of blood w/v). Pentobarbitone and diazepam, both of which produced sedation, delayed the onset of oral breathing and led to a greater degree of asphyxia during nasal obstruction. EMG activities in the genioglossus and digastric muscles were inhibited by the drugs, whereas the depth of inspiratory efforts was not. Alcohol had no apparent sedative effect, nor did it significantly affect responses to nasal occlusion. We conclude that sedating doses of pentobarbitone and diazepam depress the effectiveness of oral breathing when the nose is blocked, probably owing to their inhibitory effects on activation of muscles maintaining patency of an oral airway.


Effects of essential fatty acid contents of lipid emulsions on erythrocyte polyunsaturated fatty acid composition in patients on long-term parenteral nutrition.
The effect of the long-term intravenous infusion of 2 lipid emulsions, differing in essential fatty acid (EFA) content, on fatty acid pattern of red blood cell (RBC) was investigated in 5 patients with inflammatory bowel disease. They were randomly assigned to receive daily intravenous infusion of either a soybean emulsion or a mixed medium-chain triacyl-glycerols (MCT): soybean emulsion, followed by the other, each for a period of 3 months. The soybean emulsion contained exclusively long-chain triacylglycerols (LCT) with 54% of C18:2n-6 and 6% of C18:3n-3. The mixed emulsion consisted of a 50:50 (w:w) mixture of soybean LCT and MCT, providing half the amount of the same EFA compared to LCT emulsion. The same phospholipid emulsifier was used in both preparations. Infusion of LCT for a 3 month period modified RBC fatty acid pattern as follows: 18:2n-6 increased, 20:4n-6 decreased as well as n-6:n-3 ratio. By contrast, infusion of MCT/LCT did not alter RBC fatty acids, and even tended to correct a pattern altered by the previous LCT infusion. The study demonstrates that soybean LCT provides an excess of C18: 2n-6 which affects the balance between RBC fatty acids in adult patients. Decreasing the intake of C18:2n-6 and C18: 3n-3, by using a mixed MCT/LCT emulsion, appears more appropriate for keeping a balanced pattern.


Platelet production using adipose-derived mesenchymal stem cells: Mechanistic studies and clinical application.
Megakaryocytes (MKs) are platelet progenitor stem cells found in the bone marrow. Platelets obtained from blood draws can be used for therapeutic applications, especially platelet transfusion. The needs for platelet transfusions for clinical situation is increasing, due in part to the growing number of patients undergoing chemotherapy. Platelets obtained from donors, however, have the disadvantages of a limited storage lifespan and the risk of donor-related infection. Extensive effort has therefore been directed at manufacturing platelets ex vivo. Here, we review ex vivo technologies for MK development, focusing on human adipose tissue-derived mesenchymal stem/stromal cell line (ASCL)-based strategies and their potential clinical application. Bone marrow and adipose tissues contain mesenchymal stem/stromal cells that have an ability to differentiate into MKs, which release platelets. Taking advantage of this mechanism, we developed a donor-independent system for manufacturing platelets for clinical application using ASCL established from adipose-derived mesenchymal stem/stromal cells (ASCs). Culture of ASCs with endogenous thrombopoietin and its receptor c-MPL, and endogenous genes such as p45NF-E2 leads to MK differentiation and subsequent platelet production. ASCs compose heterogeneous cells, however, and are not suitable for clinical application. Thus, we established ASCLs, which expand into a more homogeneous population, and fulfill the criteria for mesenchymal stem cells set by the International Society for Cellular Therapy. Using our ASCL culture system with MK lineage induction medium without recombinant thrombopoietin led to peak production of platelets within 12 days, which may be sufficient for clinical application.


Cryptic speciation of a pelagic Roseobacter population varying at a few thousand nucleotide sites.
A drop of seawater contains numerous microspatial niches at the scale relevant to microbial activities. Examples are abiotic niches such as detrital particles that show different sizes and organic contents, and biotic niches resulting from bacteria-phage and bacteria-phytoplankton interactions. A common practice to investigate the impact of microenvironments on bacterial evolution is to separate the microenvironments physically and compare the bacterial inhabitants from each. It remains poorly understood, however, which microenvironment primarily drives bacterioplankton evolution in the pelagic ocean. By applying a dilution cultivation approach to an undisturbed coastal water sample, we isolate a bacterial population affiliated with the globally dominant Roseobacter group. Although varying at just a few thousand nucleotide sites across the whole genomes, members of this clonal population are diverging into two genetically separated subspecies. Genes underlying speciation are not unique to subspecies but instead clustered at the shared regions that represent ~6% of the genomic DNA. They are primarily involved in vitamin synthesis, motility, oxidative defense, carbohydrate, and amino acid utilization, consistent with the known strategies that roseobacters take to interact with phytoplankton and particles. Physiological assays corroborate that one subspecies outcompetes the other in these traits. Our results indicate that the microenvironments in the pelagic ocean represented by phytoplankton and organic particles are likely important niches that drive the cryptic speciation of the Roseobacter population, though microhabitats contributed by other less abundant pelagic hosts cannot be ruled out.


[Assessment of the tetanus immune status in plasma donors of the Blood Donor Service of the Bavarian Red Cross].
Tetanus is nowadays largely under control, as a result of the preventive immunization programme. This prophylactic measure is important also because there is no specific treatment. In Germany tetanus occurs almost exclusively in elderly, not adequately immunized persons. This study determined the existing immune status of plasma donors in the region of Ingolstadt, Bavaria. Tetanus IgG antibody concentrations were measured with the ELISA test in serum of 1742 plasma donors (891 women, 851 men, age range 18-64 years). An adequately protective immunity against tetanus was found in 98.7% of men and 94.1% of women, while 5 women and 3 men had no protection. Demographic data indicated that the immunization protected males longer than females, regardless of age, especially in those over 50 years of age (85% of females, 99% of males). Adequate tetanus protection was achieved in the overwhelming majority of test subjects. This demonstrates that the prevalence of protection is lower in females than in males, a difference most marked in those over 50 years of age. It is important that this age group in particular should, as part of health care, be informed by their medical practitioner of the dangers of tetanus and the advantages of immunization.


Plasmon expedited response time and enhanced response in gold nanoparticles-decorated zinc oxide nanowire-based nitrogen dioxide gas sensor at room temperature.
A highly sensitive and rapidly responsive nitrogen dioxide (NO2) gas sensor based on gold (Au) nanoparticles (NPs)-decorated zinc oxide (ZnO) nanowires (NWs) is presented. The Au NPs decoration was conducted onto ZnO NWs with and without a (3-aminopropyl)triethoxysilane (APTES) layer on their surface by using the electrostatic force. The samples without the APTES layer exhibited high NO2 gas sensitivity (i.e. expedited response time and enhanced gas response) due to localized surface plasmon resonance (LSPR) of the Au NPs; in particular, the NO2 gas response and the response time were increased by three times and shortened by 86%, respectively, compared with the undecorated ZnO NWs. The presence of the APTES layer improved the Au NPs attachment, but hindering the gas adsorption on the ZnO NWs surface, as proven by the observed photocurrent and gas response. Our findings imply that the response time of semiconductor gas sensors can be remarkably expedited by the LSPR effect, which is useful for developing practical gas sensors.


A new surfactant series, the N-alkylamino-1-deoxylactitols: application for extraction of 'op' opiate receptors from frog brain.
A new series of surfactants, the N-alkylamino-1-deoxylactitols, was prepared and employed to extract 'op' opiate receptors from frog brain. These surfactants are both cheap and convenient to prepare. Receptors were reproducibly extracted in a good yield using N-nonylamino-1-deoxylactitol. This derivative, which was not denaturing during the extraction process, could thus be used instead of the more costly digitonin, whose rather variable purity affects yield.


Factors influencing apparent diffusion coefficient value in extrahepatic cholangiocarcinoma: A retrospective study.
Most cases of extrahepatic cholangiocarcinoma (ECC) show various degrees of hyperintensity on diffusion-weighted imaging (DWI) and hypointensity on apparent diffusion coefficient (ADC). However, the factors influencing ADC values in ECC have not yet been explored extensively. Therefore, this study explored the independent factors influencing ADC values in ECC. A total of 88 patients with ECC confirmed by surgical pathology were retrospectively assessed. All patients underwent abdominal magnetic resonance imaging (MRI) at 3.0 T and ADC values of the tumor were measured. The correlation between ADC values and multiple clinicopathological features in ECC was analyzed, and independent factors influencing the ADC values in ECC were explored further. The ADC value of the tumor showed a significant difference in different perineural invasion group (p = 0.048), microvascular invasion group (p = 0.001), vascular endothelial growth factor expression group (p < 0.001), lymphatic status group (p = 0.003), and differentiation degree (DD) group (p < 0.001). However, there were no significant differences in different sex (p = 0.715), tumor location (p = 0.659), and degree of T stage (p = 0.879). Moreover, ADC value was negatively correlated with microvascular density (r = -0.725, p < 0.001) and lesion size (r = -0.244, p = 0.023). Nevertheless, there was no correlation between ADC value and patient age (r = 0.026, p = 0.812). Further regression analysis indicated that ADC value was independently associated with pathological DD of ECC (R2 = 0.678, p < 0.001) but not with other clinicopathological factors (p > 0.05). ADC value of ECC is independently correlated with pathological DD of ECC, indicating that ADC value is a potential imaging biomarker for predicting the degree of ECC malignancy.


Oral ACTH (H.P. Acthar(®)Gel) inhibits IL-1 and IL-17 secretion in humans.
We have shown that oral corticotropin hormone (ACTH) decreased clinical score, inflammatory foci and T(eff) IL-17 in fed and adoptive transferred recipient mice with experimental autoimmune encephalomyelitis (EAE). Therefore, we determined whether oral administration of ACTH had immunological and endocrinological effects and was safe in humans. Three groups of three healthy adult volunteers were assayed for total serum ACTH, cortisol and a set of pro-inflammatory and counter-regulatory cytokines after ingested dose(s) of ACTH 4 IU (n=3), 41 IU (n=3), or 123 IU (n=3) over 5 days. There were no safety issues during the trial. There was no increase in total ACTH levels after day 1 or day 5. There was no significant increase in total cortisol among the groups comparing day 1 to day 5. There were significant decreases in the inflammatory cytokine IL-1 and IL-17 secretion at day 6 compared to baseline with the 123 IU dose but not after the 4 IU and 41 IU doses. These data provide evidence for the safety and an immunological effect of oral ACTH in humans. It is unknown if the change in IL-1 and IL-17 reflects a local GI-mediated effect or effects following systemic absorption of ACTH.


Adsorption of Olefins at Cupric Ions in Metal-Organic Framework HKUST-1 Explored by Hyperfine Spectroscopy.
Metal-organic frameworks (MOFs) represent a promising platform for gas storage and separation. In this work, adsorption of olefins in Zn-doped HKUST-1 metal-organic framework is explored with hyperfine spectroscopy. By means of electron-nuclear double resonance and hyperfine sublevel correlation spectroscopy, we detect the interaction between the electron spins of the Cu2+ sites of the MOF and the 1H nuclear spins of adsorbed C2H4 and C4H8. Further analysis of the measured spectra allows us to precisely locate the protons in the vicinity of the Cu2+ ions and thereby establish ensemble-averaged structural models of the olefin molecules adsorbed at the open metal sites of HKUST-1.


Altered intrinsic functional network connectivity is associated with impulsivity and emotion dysregulation in drug-naïve young patients with borderline personality disorder.
Despite impulse control and emotion regulation being altered in borderline personality disorder (BPD), the specific mechanism of these clinical features remains unclear. This study investigated the functional connectivity (FC) abnormalities within- and between- default mode network (DMN), salience network (SN), and central executive network (CEN) in BPD, and examined the association between aberrant FC and clinical features. We aimed to explore whether the abnormal large-scale networks underlie the pathophysiology of impulsivity and emotion dysregulation in BPD. Forty-one young, drug-naïve patients with BPD (24.98 ± 3.12 years, 20 males) and 42 healthy controls (HCs; 24.74 ± 1.29 years, 17 males) were included in resting-state functional magnetic resonance imaging analyses. Independent component analysis was performed to extract subnetworks of the DMN, CEN, and SN. Additionally, partial correlation was performed to explore the association between brain imaging variables and clinical features in BPD. Compared with HCs, BPD showed significant decreased intra-network FC of right medial prefrontal cortex in the anterior DMN and of right angular gyrus in the right CEN. Intra-network FC of right angular gyrus in the anterior DMN was significantly negatively correlated with attention impulsivity in BPD. The patients also showed decreased inter-network FC between the posterior DMN and left CEN, which was significantly negatively correlated with emotion dysregulation. These findings suggest that impaired intra-network FC may underlie the neurophysiological mechanism of impulsivity, and abnormal inter-network FC may elucidate the neurophysiological mechanism of emotion dysregulation in BPD.


Lateral-flow immunoassays for mycotoxins and phycotoxins: a review.
Natural toxin (for example mycotoxin and phycotoxin) contamination of food is of safety and economic concern, so much effort is devoted to the development of screening methods which enable the toxins to be continuously and widely monitored in food and feed. More generally speaking, rapid and non-instrumental assays for detection of a variety of food contaminants are generating ever-increasing scientific and technological interest because they enable high-throughput, economical, on-site monitoring of such contaminants. Among rapid methods for first-level screening of food contaminants, lateral-flow immunoassay (LFIA), also named immunochromatographic assay or immune-gold colloid immunoassay, has recently attracted scientific and industrial interest because of its attractive property of enabling very rapid, one-step, in-situ analysis. This review focuses on new aspects of the development and optimization of lateral-flow devices for mycotoxin and phycotoxin detection, including strategies for management of matrix interference and, particularly, for investigation of the improvements achieved by signal-enhancing strategies or by application of non-gold nanoparticle signal reporters.


Component-based development for supporting workflows in hospitals.
Changing requirements for health care information systems force the development of an open, modular architecture in which components can be integrated. This offers a flexible means for integrating different (heterogeneous) systems used by different users. Selecting the components to integrate, and determining the 'right way' to integrate them, necessitates a shift in focus towards the business process to be supported. The realization of such an open, modular architecture is a difficult task. It consists of breaking down existing systems in required components and integrating these and other components. Many authors on component-based development strategies focus attention on the technological issues of component integration (do we use CORBA, DCOM/OLE, or EDI?). This paper presents an approach for determining the required components, and the way they have to be integrated, based on an analysis of the business process to be supported, and the information systems currently used.


Glucose inhibition of mutagenesis by 9-aminoacridine in Salmonella typhimurium.
Back mutation to prototrophy of the hisC3076 marker of Salmonella typhimurium has been measured following treatment with 9-aminoacridine (9AA) under conditions in which growth is either permitted or not permitted. Cells treated with 9AA in buffer (i.e. under conditions in which little or no replication was possible) were found to respond well to 9AA-induced mutagenesis. This remained true whether or not the plating medium contained trace amounts of histidine to allow residual replication of His- cells (as for example in the Ames test); yields of His+ mutants were also about the same regardless of whether the plating medium contained glucose or glycerol as the sole carbon source. By contrast, 9AA-induced mutagenesis was essentially abolished when cells were treated in buffer containing 1% glucose (i.e. under conditions which strongly favoured replication). Glucose inhibition of 9AA-induced mutagenesis began to be apparent at glucose concentrations of about 0.02%, whilst total abolition was observed at about 0.2%. In addition, glucose inhibition was found to be dependent on the concentration of 9AA, the induced mutation rate increasing at levels of up to 100-150 micrograms/ml of 9AA and then declining steeply at higher levels. Further kinetic studies indicated that glucose could depress the 9AA-induced mutation rate significantly even in cells exposed to the mutagen for up to 18 min prior to the addition of glucose, whilst inhibition of 9AA mutagenesis by glucose was both temporary and reversible.


An anatomical and connectivity atlas of the marmoset cerebellum.
The cerebellum is essential for motor control and cognitive functioning, engaging in bidirectional communication with the cerebral cortex. The common marmoset, a small non-human primate, offers unique advantages for studying cerebello-cerebral circuits. However, the marmoset cerebellum is not well described in published resources. In this study, we present a comprehensive atlas of the marmoset cerebellum comprising (1) fine-detailed anatomical atlases and surface-analysis tools of the cerebellar cortex based on ultra-high-resolution ex vivo MRI, (2) functional connectivity and gradient patterns of the cerebellar cortex revealed by awake resting-state fMRI, and (3) structural-connectivity mapping of cerebellar nuclei using high-resolution diffusion MRI tractography. The atlas elucidates the anatomical details of the marmoset cerebellum, reveals distinct gradient patterns of intra-cerebellar and cerebello-cerebral functional connectivity, and maps the topological relationship of cerebellar nuclei in cerebello-cerebral circuits. As version 5 of the Marmoset Brain Mapping project, this atlas is publicly available at https://marmosetbrainmapping.org/MBMv5.html.


Umbilical vein interleukin-6 levels in very low birth weight infants developing intraventricular hemorrhage.
To assess the relationship between perinatal infection/inflammation as reflected by umbilical vein interleukin-6 (IL-6) levels and the development of periventricular-intraventricular hemorrhage (IVH) in very low birth weight (VLBW) infants, we tested the hypothesis that VLBW infants who develop IVH have higher concentrations of IL-6 in an umbilical vein sample compared to infants without IVH. An inception cohort of 69 VLBW infants was followed from birth until discharge or death to determine the development of IVH by serial neuroultrasounds. Umbilical vein IL-6 levels were measured using commercially available ELISA kit (Endogen Laboratories, Woburn, MA) and compared in IVH and control cohorts. Twenty-two (32%) infants developed IVH, including 18 (82%) with grade I or II and 4 (18%) with grade III or IV. One of these infants also developed periventricular leukomalacia. The umbilical vein IL-6 levels were significantly elevated in infants with IVH with median value of 87 pg/ml (25th percentile value 30 pg/ml and 75th percentile value 310 pg/ml) compared with infants without IVH, with a median value of 0 pg/ml (25th percentile value 0 pm/ml and 75th percentile value 4 pg/ml) (P = 0.007). Umbilical vein IL-6 levels are elevated in neonates who subsequently develop IVH.


Design, synthesis and biological evaluation of 2-phenylquinoline-4-carboxamide derivatives as a new class of tubulin polymerization inhibitors.
A novel series of 2-phenylquinoline-4-carboxamide derivatives was synthesized, characterized and evaluated for its antiproliferative activity against five cancer cell lines, Hela, SK-OV-3, HCT116, A549 and MDA-MB-468, and a normal human fetal lung fibroblastic cell line, MRC-5. Among them, compound 7b displayed potent cytotoxic activity in vitro against SK-OV-3 and HCT116 cell lines with IC50 values of 0.5 and 0.2μM, respectively. In general, the antiproliferative activity was correlated with the binding property of the colchicine binding site and inhibitory effect on tubulin polymerization. In addition, immunofluorescence and flow cytometry analysis revealed that selected compounds caused disruption of the mitotic spindle assembly and G2/M phase arrest of the cell cycle, which correlated with proliferation inhibitory activity. Molecular docking analysis demonstrated the interaction of 7b at the colchicine binding site of tubulin. These results indicate these compounds are promising inhibitors of tubulin polymerization for the potent treatment of cancer.


Intermittent mandatory ventilation: an alternative weaning technic. A case report.
Many variations of measurement have been proposed for determining when a patient may be weaned from artificial ventilation. The present case report describes successful use of intermittent mandatory ventilation for weaning a patient when measurements had indicated weaning would not be possible.


Custom-made endograft with left subclavian artery branch in a patient with Takayasu aortitis complicated by type-B dissection and inflammatory involvement of the epiaortic vessels.
Type-B aortic dissection in a patient affected by Takayasu disease is a rarely described condition and its management can be challenging. A 47-year-old woman with Takayasu aortitis and previous aortic valve and ascending aorta replacement was admitted to hospital for type-B aortic dissection. The recent instabilization of aortic disease, the persistence of episodes of transient chest pain and the largest size of the aneurismatic tract of thoracic descending aorta rendered an invasive approach mandatory. Since the patient presented a complete bilateral occlusion of the subclavian artery just after the origin of the vertebral artery and a subcritical, smooth, bilateral stenosis of the common carotid artery, a custom-made endograft with left subclavian artery branch was successfully positioned, thus allowing the preservation of antegrade left vertebral circulation. This is the first case reporting an entirely endovascular exclusion of type-B dissection in a patient affected by Takayasu aortitis using a custom-made endograft with a subclavian branch allowing the preservation of the antegrade flow to left vertebral artery.


Common themes in the assembly and architecture of activating immune receptors.
Each of the many different cell types of the immune system expresses one or several activating receptors which serve a central role in the cell's surveillance function. Many of these cell-surface receptors share a distinctive modular design that consists of a ligand-binding module with no intrinsic signalling capability that is non-covalently associated with one or more dimeric signalling modules. Receptor assembly is directed by unique polar contacts within the transmembrane domains, whereas extracellular contacts can contribute to stability and specificity. This Review discusses the structural basis of receptor assembly and the implications of these findings for the mechanisms of receptor triggering.


[The case manager, a geriatrics healthcare coordinator].
The case manager mobilises the resources available within a geographic sector determined by the Centre for the autonomy and integration of Alzheimer's patients in order to respond to complex cases of elderly patient care.


Metal wet deposition in the Three Gorges Reservoir (TGR) region of Southwest China.
Metal wet deposition has become an environmental concern because of its threats to soil or water quality and human health. This study was to collect rainfall waters in 2016 from seven sites, representing urban, town, rural, and wetland, within the Three Gorges Reservoir (TGR) region of Southwest China, determine the metal concentration and flux (Zn, Mn, Cu, As, Cd, Pb), and identify their possible sources. Results indicated that Zn was the most abundant metal with a concentration of 16.92 μg L-1 in fall and 19.91 μg L-1 in winter and flux of 4.71 mg m-2 in fall, while Cd was the least with a monthly mean concentration of 0.02-0.37 μg L-1. Among the seven sites, urban (FL) had the highest values of both concentrations of metals (Zn, Cu, Pb) and fluxes of metals (Mn, As), which significantly differed from the other sites. Component and redundancy analysis suggested that fossil fuel and biomass combustion be a potential metal source. Enrichment factors, box model, and potential ecological risk index showed that the TGR water quality could face a high risk due to wet metal deposition, especially Cd. Data could provide a valuable aid in mitigating metal pollution, developing the best watershed management practices, as well as safeguarding water quality and human health in the TGR region or other reservoir regions.


Author Correction: Apparent diffusion coefficient histogram in breast cancer brain metastases may predict their biological subtype and progression.
A correction to this article has been published and is linked from the HTML and PDF versions of this paper. The error has been fixed in the paper.


NADPH metabolism determines the leukemogenic capacity and drug resistance of AML cells.
The mechanism by which redox metabolism regulates the fates of acute myeloid leukemia (AML) cells remains largely unknown. Using a highly sensitive, genetically encoded fluorescent sensor of nicotinamide adenine dinucleotide phosphate (NADPH), iNap1, we find three heterogeneous subpopulations of AML cells with different cytosolic NADPH levels in an MLL-AF9-induced murine AML model. The iNap1-high AML cells have enhanced proliferation capacities both in vitro and in vivo and are enriched for more functional leukemia-initiating cells than iNap1-low counterparts. The iNap1-high AML cells prefer localizing in the bone marrow endosteal niche and are resistant to methotrexate treatment. Furthermore, iNap1-high human primary AML cells have enhanced proliferation abilities both in vitro and in vivo. Mechanistically, the MTHFD1-mediated folate cycle regulates NADPH homeostasis to promote leukemogenesis and methotrexate resistance. These results provide important clues for understanding mechanisms by which redox metabolism regulates cancer cell fates and a potential metabolic target for AML treatments.


Laryngeal resistance before and after minor surgery: endotracheal tube versus Laryngeal Mask Airway.
The placement of an endotracheal tube (ETT) may promote laryngeal swelling, which is an important cause of upper airway obstruction after extubation. The authors hypothesized that laryngeal swelling after ETT placement increases laryngeal resistance and tested that hypothesis by comparing postoperative laryngeal patency between patients with ETT placement and those with a Laryngeal Mask Airway trade mark (LMA). Fourteen adult patients who underwent elective minor surgeries were randomly allocated to two groups whose airway would be managed through ETTs (the ETT group) or LMAs (the LMA group) during the surgery. While maintaining at sevoflurane 1 minimum alveolar concentration, the authors measured laryngeal resistance before and after surgery, during both spontaneous breathing and mechanical ventilation under complete paralysis. In addition, they endoscopically measured the vocal cord angle under complete paralysis. In association with marked swelling of the vocal cords, the vocal cord angle significantly decreased after surgery in the ETT group, whereas the angle did not change in the LMA group. Laryngeal resistance during mechanical ventilation significantly increased only in the ETT group. Laryngeal resistance during spontaneous breathing significantly increased after surgeries in both groups. Postoperative laryngeal resistance increases at least in part because of laryngeal swelling in patients with ETT placement, whereas alteration of laryngeal neural control mechanisms has been also indicated. The use of the LMA trade mark has an advantage over ETT placement in order to avoid postoperative laryngeal swelling.


Generation of cytotoxic monoclonals against AK-5 histiocytoma: conjugation with daunomycin and use in chemotherapy.
We have successfully generated cytotoxic monoclonal antibodies against a rat histiocytoma, AK-5. Monoclonal antibodies obtained after fusing immunized rat splenocytes with SP2/0 myeloma, were cytotoxic to AK-5 cells in the presence of complement. These monoclonals were highly specific and did not show any cross reactivity with normal cells and ascitic tumors such as Zajdela ascites hepatoma or Meth A. One of the antibodies was conjugated to daunomycin and used in the chemotherapeutic treatment. Total regression of AK-5 histiocytoma was obtained after injection of daunomycin-MAb conjugate into tumor bearing animals suggesting the specific targeting of the antineoplastic drug to the tumor. The histology of the tumor sections showed extensive necrosis of the tumors after treatment of the animals with drug-MAb conjugate.


Validation of a Lévy electron energy straggling model for an Elekta Synergy® linear accelerator.
In this study, an EGSnrc based Monte Carlo electron model was validated for an Elekta Synergy® 160-leaf Agility™ linear accelerator. A previously reported electron energy straggling model based on a Lévy distribution was tested against water tank measurements and a specially designed heterogeneous multi-layered phantom. This included PDD, beam profile, and relative output factor (ROF) comparison. All data passed a 2%/2 mm gamma criterion with the exception of some ROF data, which showed discrepancies of up to 2.7%. BEAMnrc was used to accurately model the linac that included the improved exit electron energy spectrum based on a Lévy distribution. The resulting BEAMnrc phase space files were used as sources in DOSXYZnrc for water tank dose distribution simulations consisting of 6 electron beam energies, 11 field sizes, and source-to-surface distances (SSDs) of 95 and 100 cm. Evaluation parameters included PDD, dose profiles, and relative output factors, as well as phantom PDD and dose profile measurements with EBT3 gafchromic film. The improved exit electron beam energy spectrum caused simulated data to comply with measured data (PPD's and dose profiles) with a 100% pass rate using a 2%/2 mm criterion except for some relative output factors that deviated by 2.7% from measured ones in water. This was observed for both 95 and 100 cm SSD data. Good agreement was obtained between film and simulation data within 2% in more than 90% of PDD and profile measurements. The Lévy based energy straggling model for electron beams allowed for accurate electron beam characterization in water tank and phantom measurements.


Risk of colonic neoplasia after proctectomy for rectal cancer in hereditary nonpolyposis colorectal cancer.
To define the neoplastic risk in the remaining colon after proctectomy for rectal cancer in patients with hereditary nonpolyposis colorectal cancer (HNPCC). The extent of surgery for rectal cancer in HNPCC is controversial. In determining which operation to perform, surgeons and patients must consider cancer risk in the remaining colon as well as functional consequences of removing the entire colorectum. The natural history of colon neoplasia in this situation is understudied and is not well-defined. A single-institution hereditary colorectal cancer database was queried for patients meeting Amsterdam criteria and with rectal cancer. Patient demographics, surgical management, and follow-up were recorded. Fifty HNPCC patients with a primary diagnosis of rectal cancer treated by proctectcomy were included. Detailed follow-up colonoscopy data were available for 33 patients. Forty-eight high-risk adenomas developed in 13 patients (39.4%). Five patients (15.2%) developed metachronous adenocarcinoma at a median of 6 years (range 3.5-16) after proctectomy, including 3 at advanced stage. One of these patients developed a high-risk adenoma before cancer. Mean interval between the last normal colonoscopy and cancer discovery was 42 months (range 23.8-62.1) with one developing within 2 years. Thus, 17 of 33 patients (51.5%) developed high-risk adenoma or cancer after proctectomy. Surgeons and patients need to be aware of substantial risk for metachronous neoplasia after proctectomy. Selection of operation should be individualized, but total proctocolectomy and ileoanal pouch should be strongly considered. If patients undergo proctectomy alone, close surveillance is mandatory.


The challenge of complexity in evaluating health policies and programs: the case of women's participatory groups to improve antenatal outcomes.
During the last years, randomized designs have been promoted as the cornerstone of evidence-based policymaking. Also in the field of community participation, Random Control Trials (RCTs) have been the dominant design, used for instance to examine the contribution of community participation to health improvement. We aim at clarifying why RCTs and related (quasi-) experimental designs may not be the most appropriate approach to evaluate such complex programmes. We argue that the current methodological debate could be more fruitful if it would start from the position that the choice of designs should fit the nature of the program and research questions rather than be driven by methodological preferences. We present how realist evaluation, a theory-driven approach to research and evaluation, is a relevant methodology that could be used to assess whether and how community participation works. Using the realist evaluation approach to examine the relationship between participation and action of women groups and antenatal outcomes would enable evaluators to examine in detail the underlying mechanisms which influence actual practices and outcomes, as well as the context conditions required to make it work. Realist research in fact allows opening the black boxes of "community" and "participation" in order to examine the role they play in ensuring cost-effective, sustainable interventions. This approach yields important information for policy makers and programme managers considering how such programs could be implemented in their own setting.


Orthogonally Protected 1,2-Diols from Electron-Rich Alkenes Using Metal-Free Olefin syn-Dihydroxylation.
A new method for the stereoselective metal-free syn-dihydroxylation of electron-rich olefins is reported, involving reaction with TEMPO/IBX in trifluoroethanol (TFE) or hexafluoroisopropanol (HFIP) and the addition of a suitable nucleophile. Orthogonally protected syn 1,2-diols were obtained with high levels of diastereocontrol, and these products were selectively deprotected and selectively functionalized into synthetically useful compounds.


Reconstructed covalent organic frameworks.
Covalent organic frameworks (COFs) are distinguished from other organic polymers by their crystallinity1-3, but it remains challenging to obtain robust, highly crystalline COFs because the framework-forming reactions are poorly reversible4,5. More reversible chemistry can improve crystallinity6-9, but this typically yields COFs with poor physicochemical stability and limited application scope5. Here we report a general and scalable protocol to prepare robust, highly crystalline imine COFs, based on an unexpected framework reconstruction. In contrast to standard approaches in which monomers are initially randomly aligned, our method involves the pre-organization of monomers using a reversible and removable covalent tether, followed by confined polymerization. This reconstruction route produces reconstructed COFs with greatly enhanced crystallinity and much higher porosity by means of a simple vacuum-free synthetic procedure. The increased crystallinity in the reconstructed COFs improves charge carrier transport, leading to sacrificial photocatalytic hydrogen evolution rates of up to 27.98 mmol h-1 g-1. This nanoconfinement-assisted reconstruction strategy is a step towards programming function in organic materials through atomistic structural control.


Effects of neuropeptide Y antagonists on food intake in rats: differences with cold-adaptation.
Hyperphagia followed both central neuropeptide Y (NPY) administration and the presumed increase of endogenous NPY activity after food deprivation. NPY induced greater hyperphagia in cold-adapted than non-adapted rats; fasting of comparable severity caused similar hyperphagia in the two groups. NPY-receptor-antagonist D-Tyr(27,36), D-Thr32-NPY(27,36) or functional NPY-antagonist D-myo-inositol-1,2,6-trisphosphate attenuated the hyperphagic effect of both NPY and fasting in non-adapted rats. However, while completely preventing the NPY-hyperphagia, they did not influence the fasting-induced hyperphagia in cold-adapted rats. With cold-adaptation the sensitivity to NPY and to its antagonists increases, but the hypothalamic NPY loses from its fundamental role in the regulation of food intake, and the hyperphagia seen in cold-adaptation may need some other explanation.


Engineering domain-swapped binding interfaces by mutually exclusive folding.
Domain swapping is a mechanism for forming protein dimers and oligomers with high specificity. It is distinct from other forms of oligomerization in that the binding interface is formed by reciprocal exchange of polypeptide segments. Swapping plays a physiological role in protein-protein recognition, and it can also potentially be exploited as a mechanism for controlled self-assembly. Here, we demonstrate that domain-swapped interfaces can be engineered by inserting one protein into a surface loop of another protein. The key to facilitating a domain swap is to destabilize the protein when it is monomeric but not when it is oligomeric. We achieve this condition by employing the "mutually exclusive folding" design to apply conformational stress to the monomeric state. Ubiquitin (Ub) is inserted into one of six surface loops of barnase (Bn). The 38-Å amino-to-carboxy-terminal distance of Ub stresses the Bn monomer, causing it to split at the point of insertion. The 2.2-Å X-ray structure of one insertion variant reveals that strain is relieved by intermolecular folding with an identically unfolded Bn domain, resulting in a domain-swapped polymer. All six constructs oligomerize, suggesting that inserting Ub into each surface loop of Bn results in a similar domain-swapping event. Binding affinity can be tuned by varying the length of the peptide linkers used to join the two proteins, which modulates the extent of stress. Engineered, swapped proteins have the potential to be used to fabricate "smart" biomaterials, or as binding modules from which to assemble heterologous, multi-subunit protein complexes.


The impact of type of assistance on characteristics of peritonitis in elderly peritoneal dialysis patients.
The elderly patients are the fastest-growing end-stage renal disease (ESRD) population in Taiwan. Assisted peritoneal dialysis (PD) has been employed to overcome the barriers to PD. The aim of this retrospective, single-center study was to describe the status of assisted PD and the impact of type of assistance on peritonitis in elderly patients in Taiwan. One hundred and two patients initiated PD at the age of 65 or older between 2000 and 2008; 79 episodes of peritonitis occurred during the follow-ups. The patients and episodes of peritonitis were divided into three groups based on the type of assistance: (1) self-care: patients performing dialysis independently, (2) family: patients whose dialysis was performed by family, (3) caregiver: patients whose dialysis was performed by a private caregiver. Patient characteristics and incidence, etiology and outcomes of peritonitis were compared. There were 26 (25.5%), 44 (43.1%), and 32 (31.4%) patients in the self-care, family, and caregiver groups, respectively. The overall peritonitis rate was 1/33 patient-months. Patients in the caregiver group were older and had more comorbidities than the self-care group. They had a trend of higher overall peritonitis rate (1/24 patient-months, P = 0.077) and fungal peritonitis rate (P = 0.060) compared to the self-care and family groups, but this was statistically non-significant. Three-fourths of elderly PD patients in the present study required assistance from family members or private caregivers. Caregiver-assisted patients were significantly older and had more comorbidities. Also, a non-significant trend of higher peritonitis incidence was observed in these patients.


Functional, textural, and rheological properties of mixed casein micelle and pea protein isolate co-dispersions.
In the midst of rising consumer health and environmental concerns, pea protein has increased in popularity as an alternative to animal-origin proteins. However, the use of pea protein in food systems is largely hindered by its poor functionality, including low solubility. The objective of this study was to measure the textural, functional, and rheological properties of a mixed plant- and animal-based protein system. Caseins, the major protein in bovine milk, are a known animal-based protein with optimal functional properties and high sensory acceptability. Through cold-temperature homogenization, insoluble pea proteins were incorporated with casein micelles in a stable, mixed, colloidal dispersion. Three blends with various casein-to-pea ratios (90:10, 80:20, 50:50) were prepared and analyzed. We hypothesized that incorporation with casein micelles would improve the poor functional properties of pea protein, and thus increase its potential uses in the food industry as a functional ingredient. The protein blend successfully underwent chymosin coagulation, a key ability of caseins, and formed protein gels with textures similar to commercial queso fresco and hard tofu. The 50% casein micelle:50% pea protein blend had better emulsification properties than pea protein alone. In contrast, this blend had the same foaming properties as pea protein alone. The mixed protein blends had similar rheological properties to skim milk, thus increasing their potential applications in the food industry. These results serve as a starting point to begin fully understanding the interactions between pea protein isolate and casein micelles combined via low-temperature homogenization and the effect on their techno-functional properties.


Renal tumors involving the inferior vena cava: plan for management.
Our experience in the management of 12 malignant renal tumors involving the inferior vena cava is analyzed and a plan to manage the different degrees of caval involvement is discussed. The use of Pringle maneuver to control hepatic circulation during removal of suprahepatic caval extensions is recommended. Followup to date supports aggressive operative management in these patients.


A novel electroporation device for gene delivery in large animals and humans.
Intramuscular injection of plasmid DNA followed by electrical stimulation (electroporation) is an efficient method for achieving therapeutic levels of encoded proteins or eliciting efficient immune responses in smaller animals such as mice and rats. Electroporation in larger animals and humans poses new technical challenges, the main difficulty being to maintain efficacy while limiting invasiveness and pain. Here we present data using a new device for combined injection and electroporation in large animals and humans. The device injects DNA through two needles during insertion into the muscle and thus distributes the injection volume along the needles which also serve as electrodes. Since the electrical field is strongest close to the needle-electrode, a near perfect match between the DNA and the electric field is achieved. We show that using moderate amounts of DNA: (1) muscle tissue is transfected along the entire length of the needle path, (2) the efficacy is higher compared to when the DNA is injected between the electrodes, (3) level of protein expression can be tightly controlled by the number of treatments, and (4) efficient immunization is achieved.


Ag8SnS6: a new IR solar absorber material with a near optimal bandgap.
We report the synthesis and photovoltaic properties of a new ternary solar absorber - Ag8SnS6 nanocrystals prepared by successive ionic layer adsorption reaction (SILAR) technique. The synthesized Ag8SnS6 nanocrystals have a bandgap E g of 1.24-1.41 eV as revealed from UV-Vis and external quantum efficiency (EQE) measurements. Its photovoltaic properties were characterized by assembling a liquid-junction Ag8SnS6 sensitized solar cell for the first time. The best cell yielded a J sc of 9.29 mA cm-2, a V oc of 0.23 V, an FF of 31.3% and a power conversion efficiency (PCE) of 0.64% under 100% incident light illumination using polysulfide electrolyte and Au counter electrode. The efficiency improved to 1.43% at a reduced light intensity of 10% sun. When the polysulfide was replaced by a cobalt electrolyte with a lower redox level, the V oc increased to 0.54 V and PCE increased to 2.29% under 0.1 sun, a respectable efficiency for a new solar material. The EQE spectrum covers the spectral range of 300-1000 nm with a maximum EQE of 77% at λ = 600 nm. The near optimal E g and the respectable photovoltaic performance suggest that Ag8SnS6 nanocrystals have potential to be an efficient IR solar absorber.


[Epidemiology of human babesiosis in Europe. Prophylactic results].
After exploring the ecology and biology of Ixodes ricinus, the vector of M. divergens, which causes human babesiosis in Europe, the author draws conclusions regarding the epidemiological features of the disease and its control.


A directly GP130-targeting small molecule ameliorates collagen-induced arthritis (CIA) by inhibiting IL-6/GP130 signalling and Th17 differentiation.
Rheumatoid arthritis is a chronic inflammatory disease associated with joint inflammation and destruction driven by T helper 17 (Th17) cells. Interleukin-6 (IL-6) is secreted by many cell types, including macrophages and synovial fibroblasts. It induces the differentiation and function of Th17 cells that can increase lymphocytic infiltration in the joint. LMT-28 can suppress IL-6 signalling through direct binding to glycoprotein-130 and alleviate inflammatory diseases such as rheumatoid arthritis and inflammatory bowel disease. The purpose of this study was to assess whether LMT-28 could potently inhibit Th17 differentiation and to determine the mechanism involved in the attenuating effect of LMT-28 on rheumatoid arthritis through the IL-6 signalling pathway. LMT-28 reduced the arthritis score and showed protective effects against bone and cartilage destruction in collagen-induced arthritis (CIA) mice. In mice with CIA, LMT-28 markedly decreased serum levels of IL-6, TNF and IL-1β compared to vehicle control. Moreover, LMT-28 attenuated Th17 cell activation in lymph nodes of CIA mice. We demonstrated that LMT-28 suppressed differentiation of Th17 in mouse splenocytes and human peripheral blood mononuclear cells (PBMCs). Additionally, LMT-28 inhibited phosphorylation of GP130, STAT3 and ERK induced by Hyper-IL-6 in human fibroblast-like synoviocytes (FLS). Collectively, these results suggest that LMT-28 can inhibit differentiated/activated-Th17 cells in rheumatoid arthritis by blocking activation of the STAT3 pathway. LMT-28 can attenuate rheumatoid arthritis by inhibiting differentiation/activation of Th17 cells and suppressing the proliferation and signalling activation of the IL-6/solubleIL-6 receptor complex stimulated FLS.


Selenium abates manganese-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats.
Excessive exposure to manganese (Mn) is associated with neurotoxicity characterized by oxidative stress, inflammation, and apoptosis induction. Selenium (Se) has been shown to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in humans and animals. The present study investigated the neuroprotective mechanism of Se in rats sub-chronically treated with Mn at 30 mg/kg body weight or orally co-treated with Se at 0.2 and 0.4 mg/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were recorded and computed with the aid of ANY-Maze (a video-tracking software) for 5-min trial, in a novel apparatus. The ANY-Maze analysis showed that Se significantly (p < 0.05) abated Mn-induced locomotive impairment evidenced by increased in maximum speed, total time traveled, absolute turn angle, number of line crossing, rotation and forelimb grip and decreased total time immobile, grooming, and negative geotaxis as verified by the enhanced track plot density. Furthermore, the striatum and hippocampus of the rats were excised and the levels of Mn and Se, oxidative stress markers, proinflammatory cytokines including acetylcholinesterase and caspase-3 activities were assayed. The result shows that Se abates Mn-mediated accumulation of Mn. Also, Se ameliorated Mn-induced decrease in antioxidant enzymes as well as glutathione level and increase in acetylcholinesterase activity, lipid peroxidation, proinflammatory cytokines (i.e., interleukin (IL)-6, IL-1β, tumor necrosis factor alpha), and caspase-3 activation in the striatum and hippocampus of the rats. Collectively, Se abated Mn-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Se may serve as a neuroprotective agent against Mn-mediated neurotoxicity.


Effect of valacyclovir on EHV-5 viral kinetics in horses with equine multinodular pulmonary fibrosis.
Equine herpesvirus-5 is commonly isolated from the lungs of horses with EMPF, suggesting an etiological link. Valacyclovir is used empirically to treat EMPF; however, no data is available concerning its impact on EHV-5 viral kinetics. To determine the effect of oral administration of valacyclovir on EHV-5 viral load measured by qPCR in blood, nasal secretions (NS) and BALF in horses with EMPF. Six horses diagnosed with EMPF. A prospective clinical trial was performed. Horses received 10 days of PO administered valacyclovir (loading dose 30 mg/kg, maintenance dose 20 mg/kg). Blood, NS, and BALF were collected for EHV-5 viral kinetics analyses during treatment. Blood and NS were collected every other day. BALF was collected on day 0 and day 10. There was no statistical difference in median EHV-5 viral load between day 0 and day 10 for all samples tested. In blood median EHV-5 viral load was 7676 (range 575-39 781) on day 0 and 6822 (range 1136-18 635) glycoprotein B (gB) gene copies per million cells on day 10. For NS median EHV-5 viral load was 2.944 × 106 (range 184 691-3.394 × 109 ) on day 0 and 8.803 × 106 (range 251 186-9.868 × 108 ) gB gene copies per million cells on day 10. For BALF median EHV-5 viral load was 59,842 (range 61-315 655) on day 0 and 185 083 (range 3562-542 417) gB gene copies per million cells on day 10. Valacyclovir might not be an effective short-term antiviral treatment but efficacy in treatment of EMPF is unknown.


Queer Space: Toilet Provision, Access and Inclusion in the West Midlands.
This article explores issues relating to toilet provision in queer spaces. With a specific focus on the implementation of gender neutral toilets, it interrogates both practical and symbolic issues of inclusivity and accessibility. The findings presented in this paper are based on 12 semi-structured interviews that were conducted and analysed in 2020. The data was analysed thematically, utilising an inductive approach to analysis. The results from this study highlight that spaces often considered 'inclusionary' operate within a number of 'exclusionary' frameworks. These unspoken and informal 'rules' and practices operate to exclude people considered 'undesirable' and function to uphold power structures that privilege cisgender, white gay men. This article extends our understanding of the ways in which people engage with, and access, both gender neutral and sex-segregated toilets. Through an analysis of complex issues relating to accessibility, inclusivity and the politicisation of queer spaces, this article argues that the implementation of gender neutral toilets holds strong practical and symbolic power within a heteronormative, cis-normative society. The results from this study indicate that providing more gender neutral spaces improves accessibility for a range of people, but also has significant political power in challenging cis-normative, heteronormative standards.


Determination of left ventricular mass by echocardiography in a normal population: effect of age and sex in addition to body size.
In this study, we determined the effect of age, sex, and body size on left ventricular mass. Two-dimensional-guided M-mode echocardiography was used in an assessment of 111 healthy, normal adults. Left ventricular mass was calculated with the cube function formula corrected by a regression equation to agree with autopsy estimates of left ventricular mass. Calculated left ventricular mass, indexed by body surface area and by height, was analyzed on the basis of sex and age of the study participants. Age was analyzed as a dichotomous, trichotomous, and continuous variable. The effects of age, sex, and obesity, as well as interactions, were tested within a multiple linear regression model framework. Left ventricular mass, when indexed for either body surface area or height, was greater in men than in women. For women, but not men, we found a small but significant increase in left ventricular mass with advancing age. Body mass index, an indicator of obesity, increased with aging in women but not in men and affected left ventricular mass. No significant changes were noted in left ventricular cavity size with advancing age, and the increase in left ventricular mass in women was due to increased ventricular wall thickness. The findings in this study suggest that left ventricular mass, as assessed by two-dimensional-guided M-mode echocardiography, is affected not only by sex and body size but also by age in women. This phenomenon may be related to an increase in body mass index with advancing age in women. In clinical studies that use echocardiographic left ventricular mass to diagnose left ventricular hypertrophy, these observations should be considered.


Angiography as an aid in extra-enteric gastrointestinal bleeding due to visceral artery aneurysm.
Three unusual patients with visceral artery aneurysms involving the hepatic artery, inferior pancreaticoduodenal artery, and a mesenteric branch artery are presented. Each of these lesions is unusual and all were diagnosed preoperatively. Surgical intervention was planned on the basis of angiography. In two patients with hypovolemia a simple diagnostic approach employing emergency selective angiography was formulated and successfully used.


The use of deep frozen, stored bovine blood for in vitro feeding of tsetse flies.
A method of blood preparation is described which resulted in the successful rearing of Glossina p. palpalis with in vitro feeding. Cells of defibrinated bovine blood were washed in 0.89% NaCl solution prior to deep-freezing. Cells and serum were stored (--28 degrees C) for up to four months. For feeding, both components were mixed in the volumetric proportion 1 : 1. Adenosine triphosphate was added at a concentration of 10-3 M to stimulate uptake of blood. Survival rate and mean weight of puparia remained constant over three generations while productivity increased.


Gastric motility after selective proximal vagotomy.
Effects of vagotomy on gastric motor activity were studied on 39 patients after vagotomy for gastric or duodenal ulcer by fluoroscopic examination and by monitoring of intragastric pressure using a balloon introduced into the stomach. These patients were divided into three groups according to types of vagotomy; selective proximal vagotomy (SPV), selective vagotomy (SV) and atypical selective proximal vagotomy. In atypical SPV, dorsal antral branches of vagal gastric nerves were sacrificed in addition to conventional SPV because of local conditions around the ulcer. In patients after SPV or atypical SPV, no gastric stasis was observed on fluoroscopic examination. However, marked gastric stasis with delayed emptying was a constant finding in patients after SV, especially at the early postoperative period. In recording of intragastric pressure, basic peristaltic waves of a 20-second rhythm were observed following inflation of the balloon in all patients after any type of vagotomy. In addition, an alternation of active and resting periods of motor activity and confluence of large waves at the end of active period were observed as characteristoc findings in patients after both SPV and atypical SPV. The large waves were considered to coincide with active propulsive movements seen on fluoroscopy in these patients. The results in this study confirmed that good gastric motility could be preserved in patients after SPV and even after atypical SPV.


The significance of the hairpin counter-current principle in the pathogenesis of toxic kidney lesions. An investigation of the influence of antidiuretic hormone and papaverine on hydroxyquinoline nephropathy of the rat.
The influence of antidiuretic hormone (ADH) and papaverine on hydroxyquinoline-induced nephropathy in rats was tested, using histotopochemistry, enzyme activity measurement and morphometric investigation. Hydroxyquinoline causes a marked increase in renal weight, the development of wedge-shaped foci with severely dilated tubule segments, and a simultaneous reduction in dehydrogenases, alkaline phosphatase, and alpha-naphthyl esterase. Both ADH and papaverine produced a significant inhibition of renal damage. The subjective findings were quantitatively confirmed by measurement of enzyme activity, using the microscope photometer, and by morphometric studies with the Leitz-Classimat (determination on the basis of the alkaline phosphatase reaction) of the surface percentage of brush border in the proximal tubules. A disturbance of the hairpin counter-current system is to be considered as the cause of the renal lesion. This disturbance is caused by hydroxyquinoline-induced impairment of Na+/K+ transport, especially in the thick ascending limb of Henle's loop. Our results show that the hydroxyquinoline nephropathy can be favourably influenced both by stimulation of water re-absorption and possibly also transepithelial Na+ transport (ADH), and by increasing the blood flow of the arteriolae rectae with a resultant lowering of the intratubular urine concentration (papaverine). The dependency of hydroxyquinoline nephropathy on the phylogenetically determined concentration capacity of the kidney, and the effective influencing of the condition by ADH and papaverine indicate the importance of the degree of efficiency of the medullary countercurrent system in the pathogenesis of this renal lesion.


Identification of RP1 as the genetic cause of retinitis pigmentosa in a multi-generational pedigree using Extremely Low-Coverage Whole Genome Sequencing (XLC-WGS).
Next-generation sequencing (NGS) technologies are decisive for discovering disease-causing variants, although their cost limits their utility in a clinical setting. A cost-mitigating alternative is an extremely low coverage whole-genome sequencing (XLC-WGS). We investigated its use to identify causal variants within a multi-generational pedigree of individuals with retinitis pigmentosa (RP). Causing progressive vision loss, RP is a group of genetically heterogeneous eye disorders with approximately 60 known causal genes. We performed XLC-WGS in seventeen members of this pedigree, including three individuals with a confirmed diagnosis of RP. Sequencing data were processed using Illumina's DRAGEN pipeline and filtered using Illumina's genotype quality score metric (GQX). The resulting variants were analyzed using Expert Variant Interpreter (eVai) from enGenome as a prioritization tool. A nonsense known mutation (c.1625C > G; p.Ser542*) in exon 4 of the RP1 gene emerged as the most likely causal variant. We identified two homozygous carriers of this variant among the three sequenced RP cases and three heterozygous individuals with sufficient coverage of the RP1 locus. Our data show the utility of combining pedigree information with XLC-WGS as a cost-effective approach to identify disease-causing variants.


Association of Breakfast Intake with Psychiatric Distress and Violent Behaviors in Iranian Children and Adolescents: The CASPIAN- IV Study.
To assess the relationship of breakfast intake with psychiatric distress and violent behaviors among Iranian children and adolescents. This national survey was conducted among 14,880 students, aged 6-18 y. They were selected by stratified multistage sampling method from urban and rural areas of 30 provinces of Iran. Breakfast intake, psychiatric distress, and violent behaviors were assessed by a questionnaire prepared based on the Global school-based student health survey of the World Health Organization. The data were analyzed by the STATA package. The participation rate was 90.6 %. The percentage of psychiatric distress among breakfast skippers, semi-skippers and non-skippers was 13.4-50.4, 10.1-41.9, and 7.0-33.3 % respectively. The prevalence of psychiatric distress was significantly higher among breakfast skippers than semi-skippers and non-skippers (P value < 0.001). The frequency of psychiatric distress had a significant decreasing trend from breakfast skippers to non-skippers. The prevalence of violent behaviors was significantly higher among breakfast skippers than non-skippers. Students who skipped breakfast reported to be more victimized (29.2 % vs. 26.7 %, respectively, P = 0.04), bullied (21.0 % vs. 16.2 %, respectively, P < 0.001), and had more physical fight (42.6 % vs. 38.5 %, respectively, P = 0.0001) than their other counterparts. Students who regularly consumed breakfast were less likely to experience mental health disorders and violent behavior. Adhering to a regular and balanced diet, besides the awareness of parents on the importance of breakfast eating, may be an appropriate approach for preventing mental health problems and violent behavior in children and adolescents.


Pharmacists' awareness of Australia's health care reforms and their beliefs and attitudes about their current and future roles.
To explore pharmacists' awareness of Australia's health care reforms and their beliefs and attitudes about their current and future roles. Four focus groups were conducted with 32 South Australian pharmacists: two groups included community pharmacists and pharmacy owners; one included hospital pharmacists and another, consultant pharmacists. Four themes emerged: (1) poor awareness of health care reform agenda; (2) strong adherence to the supply model; (3) lack of appreciation of alternative models; and (4) communication barriers. Participants' low awareness of Australia's health care reforms and their expressed beliefs and attitudes to their current role in the health system suggest that they are not well prepared for the potential future roles expected of health professionals in the health care reform agenda.


Disseminated Mycobacterium avium-intracellulare infection in acquired immunodeficiency syndrome mimicking Whipple's disease.
We report a patient with acquired immunodeficiency syndrome whose clinical presentation and histologic features resembled Whipple's disease. The unique feature of this case was the absence of Whipple's bacillus and the presence of Mycobacterium avium-intracellulare within macrophages infiltrating the small intestinal lamina propria.


Journey to Transplant: Developing a social support network counselling intervention to improve kidney transplantation.
Kidney transplant is superior to dialysis for the treatment of end-stage kidney disease, but accessing transplant requires high patient engagement to overcome barriers. We sought to develop an educational counselling intervention for patients along with their social support networks to help patients access the waiting list. Utilizing an Intervention Mapping approach, we established a conceptual framework to develop a behavioural intervention that can be reproduced across kidney transplant centres. The approach includes needs assessment, identifying behavioural determinants and process objectives and integrating targeted behavioural change theory. The Intervention Mapping process resulted in the development of a group counselling session, titled Journey to Transplant (JtT). This intervention was designed for kidney transplant candidates along with members of their social support networks and guided by a transplant healthcare professional. The session begins with standardized educational information to improve knowledge and normalize emotional barriers to transplant. This education is followed by a tailored counselling intervention, including the presentation of the individual patient's calculated likely outcomes on the kidney transplant waiting list. Finally, JtT incorporates patient and support network goal setting to address the specific barriers for that patient in accessing kidney transplantation. A systematic Intervention Mapping approach to develop the JtT intervention helps ensure the intervention is efficacious, acceptable and feasible for transplant centres to implement. JtT engages the patient's social support network, targeting known barriers to transplant and utilizing established behaviour change theory to motivate concrete actions to improve the likelihood of kidney transplantation. This study includes a patient and family advisory committee comprised of kidney transplant candidates and their family members to guide the final language and content of the intervention guide, and the conduct of the implementation and pilot testing of the intervention. However, patients and family members were not involved in the intervention mapping development process itself described in this manuscript, which was informed by focus group data from patient and family study participants.


Synthesis and biological studies of neutral technetium (V) complexes containing NNOS donor sets.
Complexation of ligands containing an N3S donor set has been affected with [99mTc]. These are part of a ligand series of analogous structures which exhibit similar chemistry and potentially interesting biology. The complexes which have been characterized with [99Tc] as [TcOL] are neutral and lipophilic and their biological behaviour has been assessed in rats. After HPLC purification of the no-carrier added preparation, brain uptake of the tracers was greater than 1% at 15 min p.i. Muscle activity was significant with slow blood clearance.


Simultaneous measurement of oxygen and dopamine: coupling of oxygen consumption and neurotransmission.
Fast-scan cyclic voltammetry was used to simultaneously measure increases in dopamine concentration and decreases in O2 concentration evoked by brief electrical stimulation (two pulses at 10 Hz) in slices of rat caudate nucleus. Dopamine concentration began increasing immediately after the first pulse and reached a maximum within 200 ms of stimulation. The O2 concentration began to decrease 300-700 ms after onset of stimulus. Responses for both dopamine and O2 were dependent on external Ca2+ and were Cd2+ and tetrodotoxin sensitive. Only the O2 response was sensitive to CN- (0.15 mM). At short times after exposure to 50 microM ouabain, electrically stimulated dopamine overflow was increased by 150% and electrically stimulated changes in O2 concentration were unaffected. Maximum dopamine concentration was increased 28% by sulpiride (2 microM), 78% by L-DOPA (60 microM), 105% by nomifensine (10 microM) and unaffected by nialamide (10 microM). Maximum decrease in O2 concentration was increased by 25% by sulpiride and unaffected by nialamide, L-DOPA, or nomifensine. The decreases in O2 concentration are indicative of increased O2 consumption and are a measure of oxidative energy production evoked by electrical stimulation. The increase in dopamine is due to the release of dopamine balanced by uptake and serves as an indication of neurotransmitter activity. The results indicate that increases in oxidative energy production following electrical stimulation are dependent on external Ca2+ entry through Cd(2+)-sensitive channels. Possible mechanisms for this coupling are discussed.


The case for an oxidopyrylium intermediate in the mechanism of quercetin dioxygenases.
The quercetin dioxygenases (QDOs) are unusual metalloenzymes in that they display ring-opening dioxygenase activity with several different first-row transition metal ions which do not undergo redox changes during turnover. The QDOs are also unique in that the substrate binds as an η1-flavonolate rather than the η2 -bidentate mode seen in all reported model complexes. The flavonol substrates were early examples of excited state intramolecular proton transfer (ESIPT) phenomena, in which photoexcitation causes an H-atom exchange between the adjacent hydroxyl and ketone, generating an oxidopyrylium emissive state. These oxidopyryliums undergo ring-opening dioxygenations analogous to the enzymatic reactions. Our hypothesis is that lability of the divalent metal ion may allow access to a reactive oxidopyrylium intermediate via coordination switching from the oxy to ketone position, which allows reaction with O2. In this report, we use a straight-forward methylation strategy to generate a panel of flavonol and thioflavonol derivatives modeling several η1- and η2-coordination modes. Methylation of 3-hydroxythioflavone generates an air stable η1 hydroxopyrylium salt, which undergoes rapid ring-opening dioxygenation by deprotonation or photoexcitation. By comparison, the η1-methoxyflavonol does not react with O2 under any condition. We find that any of the studied flavonol derivatives, η1 or η2, which demonstrates ESIPT-like oxidopyrylium emissions undergo QDO-like ring-opening reactions with dioxygen. The implications of these results concerning the mechanism of QDOs and related dioxygenases is discussed.


Does prenatal and infancy nurse home visitation have enduring effects on qualities of parental caregiving and child health at 25 to 50 months of life?
To examine, during the 3rd and 4th years of life, the health, development, rates of child maltreatment, and living conditions of children who had been enrolled in a randomized trial of nurse home visitation during pregnancy and first 2 years of their lives. Prospective follow-up of families who had been randomly assigned to nurse-visited and comparison conditions. Study conducted in semirural community in upstate New York. Families dispersed among 14 other states during 2-year period after children's second birthdays. Four hundred women were recruited through a health department antepartum clinic and offices of private obstetricians and were registered before 30th week of pregnancy. All women had no previous live births and 85% were either teenaged (< 18 years at registration), unmarried, or from Hollingshead social classes IV or V. Analysis focused on whites, who comprised 89% of sample. Nurse home visitation from pregnancy through second year of the child's life. There were no treatment differences in the rates of child abuse and neglect or children's intellectual functioning from 25 to 48 months of age. Nurse-visited children, nevertheless, lived in homes with fewer hazards for children; they had 40% fewer injuries and ingestions and 45% fewer behavioral and parental coping problems noted in the physician record; and they made 35% fewer visits to the emergency department than did children in the comparison group. Nurse-visited mothers were observed to be more involved with and to punish their children to a greater extent than were mothers in the comparison group. The functional meaning of punishment differed between the nurse-visited and comparison families. The program does have enduring effects on certain aspects of parental caregiving, safety of the home, and children's use of the health care system, but it may be necessary to extend the length of the program for families at highest risk to produce lasting reductions in child abuse and neglect.


IL-17A enhances ADAMTS-7 expression through regulation of TNF-α in human nucleus pulposus cells.
ADMATS-7 is known to play an important role in the pathogenesis of various diseases, including cartilaginous diseases. IL-17A is an inflammatory cytokine detected in degenerative disc tissues. However, the interplay between IL-17A and ADMATS-7 in human disc degeneration is still unknown. Samples collected from 50 patients were divided into three groups according to MRI degeneration grading system score. Immunohistochemistry, RT-PCR and western Blotting were used to investigate the expression of ADAMTS-7 in NP tissues. Furthermore, a rat disc degeneration model was established, and the expression level of ADAMTS-7 was assayed using immunohistochemistry, RT-PCR and western Blotting. The human NP cells were cultured in the presence and absence of IL-17A stimulation. RNA extracts were collected, and real-time PCR was performed to determine the expression of ADAMTS-7. Moreover, ADAMTS-7 concentrations were detected in human NP cell culture supernatants by ELISA. After culturing NP cells with IL-17A (with or without Etanercept), ADAMTS-7 levels were detected in each group. ADAMTS-7 expression was dramatically elevated in both human and rat degenerative NP tissues compared with normal controls. The RT-PCR and ELISA results revealed that IL-17A could enhance the production of ADAMTS-7, while ADAMTS-7 expression dramatically decreased in the IL-17A + Etanercept group in comparison to the IL-17A alone group. Our results indicate the presence of ADAMTS-7 in human NP cells and imply its potential role in disc degeneration. Additionally, our results indicate that IL-17A induced ADAMTS-7 expression via TNF-α, which may form a molecular axis in human NP cells.


Circulating miR-181 is a prognostic biomarker for amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis (ALS) is a relentless neurodegenerative disease of the human motor neuron system, where variability in progression rate limits clinical trial efficacy. Therefore, better prognostication will facilitate therapeutic progress. In this study, we investigated the potential of plasma cell-free microRNAs (miRNAs) as ALS prognostication biomarkers in 252 patients with detailed clinical phenotyping. First, we identified, in a longitudinal cohort, miRNAs whose plasma levels remain stable over the course of disease. Next, we showed that high levels of miR-181, a miRNA enriched in neurons, predicts a greater than two-fold risk of death in independent discovery and replication cohorts (126 and 122 patients, respectively). miR-181 performance is similar to neurofilament light chain (NfL), and when combined together, miR-181 + NfL establish a novel RNA-protein biomarker pair with superior prognostication capacity. Therefore, plasma miR-181 alone and a novel miRNA-protein biomarker approach, based on miR-181 + NfL, boost precision of patient stratification. miR-181-based ALS biomarkers encourage additional validation and might enhance the power of clinical trials.


Substance P-containing nerves in the human small intestine. Distribution, ultrastructure, and characterization of the immunoreactive peptide.
Light and electron microscopic immunocytochemical techniques were used to examine the distribution and ultrastructure of substance P-immunoreactive nerves in human jejunum and distal ileum. The organization of human enteric substance P-containing nerves closely resembled that in other species. Dense arrays of varicose immunofluorescent fibers occurred in myenteric and submucous ganglia (which contained immunoreactive nerve cell bodies) and in the mucosa. There were fibers in both muscle layers, in the muscularis mucosae, and around blood vessels. Fibers in the myenteric plexus contributed to both ascending and descending pathways. Substance P-immunoreactive axon profiles contained small round and large round vesicles and were apposed to nerve cell bodies, and nonimmunoreactive and immunoreactive axon profiles. Synapselike contacts were occasionally observed on nerve cell bodies and processes. The substance P-like material was characterized by high pressure liquid chromatography and radioimmunoassay and found to be indistinguishable from the authentic undecapeptide. These results suggest that enteric nerves containing substance P may play similar roles in humans as in other species.


Mapping of mammalian beta-adrenoreceptors by use of macromolecular alprenolol derivatives. A comparison with amphibian erythrocyte receptors.
THe interaction of macromolecular alprenolol derivatives with beta-adrenoreceptors of rat heart, lung, and erythrocytes and frog erythrocytes has been studied. Macromolecular derivatives were prepared by covalently coupling alprenolol to dextrans containing a homologous series of spacer arms of various lengths. The affinity of these macromolecules for frog erythrocyte membranes increased with increasing length of spacer arm. In contrast, the affinity of these macromolecules for all mammalian membrane preparations was weak and insensitive to the length of the spacer arm. The inhibition of [3H]dihydroalprenolol binding to rat heart, lung, and erythrocyte membrane preparations by these macromolecular derivatives was more than 1000-fold less potent than inhibition by alprenolol. The results suggest different structural characteristics between mammalian and amphibian beta-adrenoreceptors; however, apparently only small differences between mammalian receptors could be distinguished with these probes.


Hospitalization for lung disease in early childhood and asthma symptoms in young adulthood.
Longitudinal studies have reported an association between early childhood lung disease and adult respiratory disease. This issue has not been addressed in the Nordic countries. We studied the association between hospitalization for lung disease in early childhood and asthma in young adulthood in a Norwegian population sample, while estimating the attributable fraction of childhood hospitalization. A population-based survey in Bergen, Norway included a random sample of 4300 subjects aged 20-44 years, of whom 80% responded. The effect of hospitalization for lung disease before the age of 2 years on asthma in adulthood was analysed by logistic and polytomous logistic regressions, adjusting for related variables. Adjusted attributable fractions were estimated from these models. The risk for different measures of asthma was significantly increased in the 103 persons reporting childhood hospitalization (airways symptoms: OR from 1.9 to 2.9; asthma medication: OR = 2.8). The associations with airways symptoms were stronger in women (OR from 2.6 to 5.3) than in men (OR from 1.4 to 2.4). Given a causal association, adjusted attributable fractions showed that childhood lung disease causing hospitalization explained 4% of asthma symptoms. Early childhood hospitalization for lung disease was related to asthma symptoms in young Norwegian adults, more strongly in women than in men. Only a minor proportion of asthma symptoms in this age group could be related to hospitalization for lung disease in early childhood.


[Characteristics of the adaptive restructurings of the digestive system during exposure to the factors of space flight].
The article presents an evaluation of the state of the digestive system in astronauts during short-term and long-term space flights. After short-term (7- or 8-day) flights, there was a transitory activation of gastrointestinal enzyme systems. After prolonged space flights, there was an increase in gastric acidity and pepsin excretion, as well as pancreatic and intestinal malfunctions. In summary, there is a transition of the digestive system to a new level of functioning.


Genomic analysis of Mycobacterium tuberculosis complex strains used for production of purified protein derivative.
The genomes of the tuberculin production strains Mycobacterium bovis AN5 and Mycobacterium tuberculosis DT were compared to genome-sequenced tubercle bacilli by using DNA microarrays. Neither the AN5 nor DT strain suffered extensive gene deletions during in vitro passage. This suggests that bovine tuberculin made from M. bovis AN5 is suitable to detect infection with presently prevalent M. bovis strains.


Crystal structure of β-benzyl dl-aspartate N-carb-oxyanhydride.
In the title racemic compound, C12H11NO5 [systematic name: benzyl 2-(2,5-dioxooxazolidin-4-yl)acetate], the oxazolidine ring is planar, with an r.m.s. deviation of 0.03 Å. The benzyl ring is almost normal to the oxazolidine ring, making a dihedral angle of 80.11 (12)°. In the crystal, inversion dimers are formed between the l- and d-enanti-omers via pairs of N-H⋯O hydrogen bonds. This arrangement is favourable for the polymerization of the compound in the solid state. The dimers are linked by C-H⋯O hydrogen bonds, forming layers parallel to the ab plane.


Recurrent lupus pneumonitis with pulmonary hemorrhage in systemic lupus erythematosus associated with chronic thyroiditis and antithyroid hormone autoantibodies.
We describe a SLE patient with repeated lupus pneumonitis and pulmonary hemorrhage. The hemorrhagic episodes were considered to be related to thrombocytopenia and lupus pneumonitis, which have responded well to treatment with moderate doses of steroids and immunosuppressant. She was also found to be suffering from chronic thyroiditis (hypothyroidism) and was positive for anti-thyroid hormone antibodies, which have not been reported before in the SLE patients with thyroid diseases.


Prediction of early graft occlusion in femoropopliteal and femorodistal reconstruction by measurement of volume flow with a transit time flowmeter and calculation of peripheral resistance.
A transit time flowmeter (Transonic TC101DTM, Transonic Inc., U.S.A.) was used for flow measurements and calculation of peripheral resistance in 48 primary femoropopliteal and femorodistal reconstructions. The results were correlated with primary graft occlusions during the first 90 postoperative days. There were 25 men and 23 women with a median age of 75 years (67-83). Eight were diabetic. Indications for surgery were rest pain (n = 23), ischaemic ulcer (n = 16), gangrene (n = 8) and popliteal aneurysm (n = 1). Measurements were made before reconstruction on the artery at the site of the distal anastomosis. After reconstruction flow measurements were made on the graft near the proximal and distal anastomoses together with a proximal graft pressure measurement. The peripheral resistance was calculated. Eleven grafts occluded and six patients died, four with patient grafts. Patients with graft occlusions had a significantly lower flow before (4 vs. 20 ml/min) and after (60 vs. 110 ml/min) reconstruction and a higher peripheral resistance, (1238 vs. 625 mPRU) than patients with patent grafts. The most significant differences were found in the femorodistal bypass grafts. The transit time flowmeter was easy to use. The flow before and after reconstruction as well as the peripheral resistance could be used for the prediction of graft function within 90 days of surgery.


Annual use and perceived need for mental health and substance treatment among people in remission from substance use disorders in the United States.
Receiving specialty substance treatment or general mental health treatment during remission from substance use disorders (SUD) may reduce odds of SUD recurrence, but little is known about prevalence of treatment or perceptions of treatment need among remitted people in the United States. Participants in the National Survey on Drug Use and Health, years 2018-2020, were considered remitted if they ever had an SUD (i.e., self-reported history of "problems with alcohol or drugs", or lifetime history of treatment for SUD) but did not meet DSM-IV criteria for substance abuse or dependence during the prior year (n = 9,295). Annual prevalence was estimated for any SUD treatment (e.g., mutual-help groups), any mental health (MH) treatment (e.g., private therapy), self-reported perceived need for SUD treatment, and self-reported unmet need for MH treatment. Generalized linear models examined effects of socio-demographics, mental illness, past-year substance use, and self-identified recovery status on outcomes. MH treatment was more common than SUD treatment (27.2% [25.6%, 28.8%] v. 7.8% [7.0%, 8.6%], respectively). Unmet need for mental health treatment was reported by 9.8% [8.8%, 10.9%], but only 0.9% [0.6%, 1.2%] perceived need for substance treatment. Age, sex, marital status, education, health insurance, mental illness, and prior year alcohol use were among the factors associated with variation in outcomes. Most people who maintained clinical remission from substance use disorders in the U.S. during the prior year did so without treatment. Remitted people report substantial unmet need for mental health treatment, but not specialized substance use treatment.


Human IgG Fc-glycosylation profiling reveals associations with age, sex, female sex hormones and thyroid cancer.
IgG functions rely on interactions of the Fc region with other proteins, which are optimized by tailoring of a conserved N-linked glycosylation at Asn-297. We conducted a study involving 735 control individuals and 138 thyroid cancer patients. Here we demonstrated that previously described age-related change in Fc-glycosylation was further characterized by definite sex specificity. In females, the incidences of most of glycosylated forms began to pose characteristic changes at ages of puberty or menopause. In addition, glycan-glycan relationships existed extensively within Fc glycosylation, which were characterized to be altered upon different states of subjects, such as age, sex and thyroid cancer. In thyroid cancer patients, detailed comparison of glycosylation incidences with control individuals yielded insight into aberrant change in IgG(1) Fc-glycosylation. This aberrant pattern was also featured by remarkable specificities of both age and sex. The receiver operating characteristic curve analysis was used to determine diagnostic values of Fc glycosylation. Finally, clinical measurement of two major female sex hormones estradiol and progesterone was conducted to determine potential associations of hormones with IgG Fc glycosylation. This study provided an important view to the associations of IgG Fc N-linked glycosylation with age, sex, female sex hormones and thyroid cancer. This article is part of a Special Issue entitled: Proteomics: The clinical link.


CgB promotes EMT and stemness via MAPK pathway in colonic neuroendocrine carcinoma.
The incidence of colorectal neuroendocrine tumors is increasing every year with poor prognosis. Members of Chromogranin family proteins have been shown to be associated with cancer metastasis; however, the role of chromogranin B in colonic neuroendocrine carcinoma (NEC) is unknown. In this study, we investigated the expression and function of CgB in colonic NEC. Using RNA-seq data from GSE 9576 and GSE 142720 datasets, we analyzed the differentially expressed genes between the normal and NEC samples, which protein levels were further validated using the Human Protein Atlas (HPA) databases. Moreover, immunohistochemistry staining and biological experiments were conducted to examine the expression and function of CgB in colonic NEC. Western blot was also performed to confirm the effect of CgB on epithelial mesenchymal transition (EMT) and its related pathways. We found that the expression level of CgB was significantly higher in colonic NEC tissues than in the adjacent tissues. The upregulation of CgB promoted cell invasion and migration as well as activated EMT and stemness. Mechanistically, both pathway enrichment analysis and Western blot analysis confirmed that CgB overexpression activated p38 MAPK and ERK pathways, while silencing CgB showed the opposite effects. Collectively, our results suggested that CgB activated p38 MAPK and ERK pathways, thereby contributing to the development of colonic NEC.


Impact of mpMRI targeted biopsy on intraoperative nerve-sparing (NeuroSAFE) during robot-assisted laparoscopic radical prostatectomy.
The aim of our study was to evaluate the impact of prostate biopsy technique (transrectal ultrasound (US)-prostate biopsy (PBx) versus multiparametric magnetic resonance imaging (mpMRI) targeted prostate biopsy (MRI-PBx) on intraoperative nerve-sparing and the rate of secondary neurovascular-bundle resection (SNR) in patients undergoing robot-assisted laparoscopic radical prostatectomy (RARP). A real-time investigation with a frozen-section examination (NeuroSAFE) microscopically excluded or confirmed prostate cancer invasion of the nerve structures resulting in preservation of the neurovascular bundle or SNR. Additionally, we analyzed risk factors related to SNR, such as longer operation time and postoperative complications. The total study cohort was stratified according to non-nerve-sparing versus nerve-sparing RARP. Patients with nerve-sparing approach were then stratified according to biopsy technique (PBx vs. MRI-PBx). Further, we compared PBx versus MRI-PBx according to SNR rate. We included a total of 470 consecutive patients, who underwent RARP for PCa at our institution between January 2016 and December 2019. Patients with a preoperative MRI-PBx had a 2.12-fold higher chance of successful nerve-sparing (without SNR) compared to patients with PBx (p < 0.01). Patients with preoperative MRI-PBx required 73% less intraoperative SNR compared to patients with PBx (p < 0.0001). Prior MRI-PBx is thus a predictor for successful nerve-sparing RARP approach. Preoperative MRI-PBx led to better oncological outcomes and less SNR. Young patients with good erectile function could benefit from a preoperative MRI-PBx before nerve-sparing RARP.