Three-dimensional analysis of the dendritic domains of on- and off-cells in the rostral ventromedial medulla.
The rostral ventromedial medulla contains two classes of physiologically defined neurons, on-cells and off-cells, that are implicated in nociceptive modulation. In a continuing effort to detail the neural circuitry that underlies the activity of these two distinct neuronal types, the three-dimensional somatodendritic morphology of on- and off-cells was studied in the cat and the rat. Following physiological characterization with intracellular recording, on- and off-cells were injected with horseradish peroxidase and sectioned in the coronal plane. Their somatodendritic arborizations were reconstructed with the aid of a computerized three-dimensional reconstruction program. There were no differences between on- and off-cells in any somatodendritic feature analyzed. On- and off-cells possess dendritic arbors that are elongated in the mediolateral axis relative to the dorsoventral and rostrocaudal axes. In the rat, the average dendritic extent was more than 1,400 microns mediolaterally but only about 800 microns in either the dorsoventral or rostrocaudal axis. All somatic and dendritic measures were greater for both cat cells than for any rat neuron. Dendrites and their tips were located predominantly in regions lateral to the soma. The center of total dendritic length was usually located within 150 microns of the soma, most frequently ventral and lateral to the soma. The present results demonstrate that the dendritic domains of neurons in the nuclei raphe magnus and reticularis paragigantocellularis pars alpha are not contained within cytoarchitechtonic boundaries. On- and off-cell dendrites are interdigitated throughout the mediolateral extent of the rostral ventromedial medulla. Since on- and off-cell dendritic domains occupy a restricted rostrocaudal plane, afferents to the rostral ventromedial medulla that are confined to a single coronal plane and those that collateralize at several levels are likely to play different roles in the control of on- and off-cell activity.


Occurrence and fate of microplastics from wastewater treatment plants assessed by a fluorescence-based protocol.
Traditional stereomicroscopy (SM) is limited for the identification of microplastics of less than 500 µm in wastewater treatment plants (WWTPs). Accordingly, novel methods for the accurate quantification of these microplastics are needed. In this study, we investigated the polymer type, morphology, size distribution, and abundance of microplastics in each unit of three selected WWTPs by SM and a fluorescence-based protocol (FR) combined with FTIR. Using the FR method, most microplastics detected in the three WWTPs were 50-200 µm in size. Polyethylene, polypropylene, and polyamide were the main polymer types, and the distributions of fibers, films, and debris were determined. Despite highly similar microplastic removal rates (78.6‒95.2% (SM) and 77.4‒94.2% (FR)) in the WWTPs by the two methods, the microplastic abundances obtained by FR (405‒6987 items/L) were approximately 2 orders of magnitude higher than the corresponding results by SM (1‒21 items/L). In addition, a considerable number of small-sized microplastics (< 500 µm) were detected in the effluents (405‒947 items/L) using FR. These results clearly reveal that microplastics in WWTPs have been seriously underestimated in most previous studies based on SM. Further research should focus on the environmental risks of small-sized microplastics from WWTPs.


The 48 bp centromeric repeat is a functionally conserved motif in great apes and man showing protein-binding properties.
The centromere-kinetochore complex is a chromosomal assembly site including repeat motifs and protein binding properties thus mediating chromosome motility and mitotic regulation. Next to the alpha-satellite DNA family as well as human satellite III DNA, contribution of other repetitive sequences has to be strongly considered in centromere function. Here, we report the identification of centromeric 48 bp motifs, isolated from chimpanzee and orang-utan using an orthologous human DNA probe. Applying Southern hybridization we show that these sequences are restricted to hominoid species. Diminishing hybrid formation in gibbons suggested that the 48 bp repeat originated approximately 25-20 million years ago. Consistently, both chimpanzee as well as human repeat probes failed to generate any hybridization signal with the monkey species Cercopithecus aethiops and Aotes trivirgatus. Sequence deviations from the consensus of human repeat monomers of 6% and 10.4% in chimpanzee and orang-utan, respectively, were found within a 16 bp region of the 48 bp repeat units. Gel mobility shift assays using chimpanzee repeat dimers as probes revealed peptide-binding properties with human and chimpanzee nuclear extracts. Species-specific DNA-protein complexes remained unaffected by competition studies and indicated the presence of at least one novel interacting protein consisting of two subunits with 90 and 95 kDa. Our data suggest that the 48 bp repeat, next to alpha-satellite DNA, provides essential sequence information for specific DNA-protein interaction and they imply phylogenetic conservation of these binding properties in primates. The complex is likely involved in the proper formation and/or function of mammalian centromeres.


Active Raman sounding of the earth's water vapor field.
The typically weak cross-sections characteristic of Raman processes has historically limited their use in atmospheric remote sensing to nighttime application. However, with advances in instrumentation and techniques, it is now possible to apply Raman lidar to the monitoring of atmospheric water vapor, aerosols and clouds throughout the diurnal cycle. Upper tropospheric and lower stratospheric measurements of water vapor using Raman lidar are also possible but are limited to nighttime and require long integration times. However, boundary layer studies of water vapor variability can now be performed with high temporal and spatial resolution. This paper will review the current state-of-the-art of Raman lidar for high-resolution measurements of the atmospheric water vapor, aerosol and cloud fields. In particular, we describe the use of Raman lidar for mapping the vertical distribution and variability of atmospheric water vapor, aerosols and clouds throughout the evolution of dynamic meteorological events. The ability of Raman lidar to detect and characterize water in the region of the tropopause and the importance of high-altitude water vapor for climate-related studies and meteorological satellite performance are discussed.


Skin Pigmentation in Gilthead Seabream (Sparus aurata L.) Fed Conventional and Novel Protein Sources in Diets Deprived of Fish Meal.
The pattern of yellowish pigmentation of the skin was assessed in gilthead seabream (Sparus aurata) fed for 12 weeks iso-proteic (45%) and iso-lipidic (20%) diets deprived of fish meal and containing either a blend of vegetable protein-rich ingredients or where graded levels of the vegetable protein blend were replaced by insect (Hermetia illucens-10%, 20% or 40%) pupae meal, poultry by-product meal (20%, 30% or 40%), red swamp crayfish meal (10%) and marine microalgae (Tisochrysis lutea and Tetraselmis suecica-10%) dried biomass. Digital images of fish fed diets differing in protein sources were analyzed by means of an automatic and non-invasive image analysis tool, in order to determine the number of yellow pixels and their dispersion on the frontal and lateral sides of the fish. The relationship between the total carotenoid concentration in the diet and the number of yellow pixels was investigated. Test diets differently affected gilthead seabream skin pigmentation both in the forefront and the operculum, due to their carotenoid content. The highest yellow pixels' number was observed with the diet containing microalgae. Fish fed poultry by-product meal were characterized by the lowest yellow pixels' number, diets containing insect meal had an intermediate coloring capacity. The vegetable control, the microalgae mix diet and the crayfish diet had significantly higher values of yellow pixels at both inspected skin sites.


Attitude of the population of German origin in the south east of Spain toward living kidney donation. In search of favorable sub-groups for promoting living kidney donation in Spain.
There is an increasing population of German origin living in the South East of Spain. To analyze the attitude toward living kidney donation in this population subgroup. A sample of German residents in the South East of Spain was taken randomly (n = 250) (November 2005-April 2006). Attitude was evaluated using a validated questionnaire. The survey was self-administered and completed anonymously. The control group comprised native Spanish citizens (n = 500). The questionnaire completion rate was 87% (n = 218). Most respondents (92%, n = 201) are in favor of living-related donation. The following variables are related to attitude to donation: (1) marital status of the respondent (p = 0.002); (2) level of education (p < 0.001); (3) attitude toward cadaveric donation (p = 0.005); (4) having had previous experience with the donation and transplantation process (p < 0.001); (5) the respondent's religion (p = 0.002); (6) the risk that they believe is involved in living kidney donation (p = 0.001), and (7) concern about 'mutilation' that could be caused by living donation (p < 0.001). Attitude toward related living kidney donation of German residents in the South East of Spain is favorable and is closely related to attitude toward cadaveric donation, fear of the after-effects of this type of donation and religious attitude.


ACTH-induced inhibition of endogenous rat brain protein phosphorylation in vitro: structure activity.
ACTH1--24 inhibits the endogenous phosphorylation in vitro of distinct SPM protein bands. Using N-terminal fragments of ACTH, the structure-activity requirements for this effect were studied. A rather complex interaction of the ACTH fragments with endogenous SPM phosphorylation was observed. The effects were not only dependent on the primary structure of the peptide used, but also on the protein band studied and the ATP/SPM ratio used in the incubation system. ACTH1--24 did not interfere with the ATP-hydrolyzing activity of the SPM preparation, nor did it influence the endogenous phosphatase activity. Therefore, a direct interaction of ACTH with SPM protein kinase(s) is likely to be responsible for its effect on phosphorylation.


Comparison of reinnervation for preservation of denervated muscle volume with motor and sensory nerve: an experimental study.
Prevention of the atrophy of denervated muscles is essential for a good outcome in facial contouring and oral reconstruction. In this study, we compared the effectiveness of end-to-end and end-to-side neurorrhaphy of the motor nerve, and end-to-end neurorrhaphy of the sensory nerve, all of which are frequently used in such reconstruction for the prevention of muscle atrophy. Wistar rats were divided into four groups: group 1, motor nerve division of semi-membranosus without repair; group 2, motor nerve division and end-to-end coaptation to the saphenous nerve; group 3, motor nerve division and end-to-side coaptation to the sciatic nerve; and group 4, motor nerve division and end-to-end repair. Measurement of semi-membranosus volume, histological evaluation and staining of neuromuscular junctions that were carried out 3 months postoperatively revealed that muscle volume preservation was larger in groups 3 and 4 than in the other two groups (p<0.05), but slightly superior in group 4 (p<0.05). There was no statistical difference between groups 2 and 1; histologically, muscle architecture was better preserved in group 2 than in group 1; reactivation of the neuromuscular junctions was observed in all except group 1. End-to-side repair of motor nerves is one of the better options for the preservation of muscle volume when end-to-end nerve repair is not indicated. Sensory protection may also provide some advantages in the preservation of muscle volume.


Surgical Management of Lymph Nodes in Melanoma.
This article provides a comprehensive evaluation of surgical management of the lymph node basin in melanoma, with historical, anatomic, and evidence-based recommendations for practice.


Is there a weekend effect in emergency surgery for colorectal carcinoma? Analysis from the German StuDoQ registry.
Higher postoperative mortality has been observed among patients who received emergency colorectal surgery on the weekend compared to during the week. The aim of this study was to determine whether the weekday of emergency surgery affects the 30-day mortality and postoperative course in emergency colorectal surgery. Prospectively acquired data from the 2010-2017 German StuDoQ|Colorectal surgery registries were analysed. Differences in 30-day mortality, transfer and length of stay (MTL30) (primary endpoints), postoperative complications, length of stay and pathological results of resected specimens (secondary endpoints) were assessed. Multivariable analysis was performed to identify independent risk factors for postoperative outcome. In total, 1,174 patients were included in the analysis. Major postoperative complications and the need for reoperation were observed more frequently for emergency colorectal surgery performed during the week compared to the weekend (23.01 vs. 15.28%, p = 0.036 and 17.96% vs. 11.11%, p = 0.040, respectively). In contrast, patients who received emergency surgery on the weekend presented with significantly higher UICC tumour stages (UICC III 44.06 vs. 34.15%, p = 0.020) compared to patients with emergency colorectal surgery on a weekday. Emergency surgery performed during the week was an independent risk factor for the development of severe postoperative complications (OR 1.69 [1.04-2.74], p = 0.033) and need for reoperation (OR 1.79 [1.02-3.05], p = 0.041) in the multivariable analysis. Emergency surgery for colorectal carcinoma in Germany is performed with equal postoperative MTL30 and mortality throughout the entire week. However, emergency surgery during the week seems to be associated with a higher rate of severe postoperative complications and reoperation.


Serum Uric Acid concentration is associated with insulin resistance and impaired insulin secretion in adults at risk for Type 2 Diabetes.
Insulin resistance (IR) predisposes to type 2 diabetes mellitus (T2DM). Although previous studies have associated serum uric acid concentration with IR in T2DM, its association with impaired insulin secretion and beta-cell dysfunction in subjects at risk for developing T2DM remains uncertain. Thus, we aimed to analyze the association of serum uric acid concentration with IR using surrogate insulin resistance/secretion and beta-cell function indices in subjects at risk for developing T2DM. This is a cross-sectional study that included 354 subjects who underwent an oral glucose tolerance test who had at least two risk factors for T2DM without any chronic disease. Participants were 51±8 years old, 72.2% were women, had a mean body mass index of 29.9±6.5kg/m2 and mean serum uric acid concentration of 5.7±1.3mg/dL. HOMA-IR, first-phase insulin secretion (S1PhOGTT), second-phase insulin secretion (S2PhOGTT), Matsuda and disposition indices were significantly correlated with serum uric acid concentrations (r=0.239, r=0.225, r=0.201, r=-0.287, r=-0.208; respectively). After multiple linear regression analysis, serum uric acid concentration was independently associated with HOMA-IR (β=0.283), HOMA-B (β=0.185), S1PhOGTT (β=0.203), S2PhOGTT (β=0.186), and Matsuda Index (β=-0.322). A serum uric acid concentration of 5.5mg/dL had the best sensitivity/sensibility to identify subjects with IR (HOMA-IR ≥2.5). Serum uric acid concentration is significantly associated with IR and impaired insulin secretion, but not with beta-cell dysfunction, in subjects at risk for developing T2DM.


Improving performance of a five-zone simulated moving bed chromatography for ternary separation by simultaneous use of partial-feeding and partial-closing of the product port in charge of collecting the intermediate-affinity solute molecules.
The performance of a five-zone simulated moving bed (SMB) chromatographic process for ternary separation has been improved to a certain extent in previous researches by applying either a partial-feeding (PF) or a partial-closing of the extract-2 port (PCE(2)) to its operation. To make a further improvement, the strategy of applying both PF and PCE(2) simultaneously to the five-zone SMB operation was proposed in this study. The results from both equilibrium-theory analysis and detailed simulation proved that the proposed strategy, which was called PF-PCE(2) in this article, had the benefit of a synergy between the individual merits of PF and PCE(2) in the five-zone SMB performance. As a consequence, the PF-PCE(2) mode could surpass the PF and the PCE(2) modes by a wide margin and the standard mode by a much wider margin in the aspects of ternary-separation performance and throughput. For the separation system considered, the PF-PCE(2) mode was found to achieve more than 100% improvement, compared to the standard mode. Furthermore, such advantage of the PF-PCE(2) over all the other modes was greater as the selectivity between the intermediate-affinity and the highest-affinity components was reduced.


[Spontaneous pneumothorax in pregnancy: description of a case and review of the literature].
A case of pneumothorax during the 8th week of pregnancy is described. The literature is reviewed. We highlight the rareness of the case and discuss of possible relationship with protector hormonal factors.


Intrinsic maturation of sleep output neurons regulates sleep ontogeny in Drosophila.
The maturation of sleep behavior across a lifespan (sleep ontogeny) is an evolutionarily conserved phenomenon. Mammalian studies have shown that in addition to increased sleep duration, early life sleep exhibits stark differences compared with mature sleep with regard to sleep states. How the intrinsic maturation of sleep output circuits contributes to sleep ontogeny is poorly understood. The fruit fly Drosophila melanogaster exhibits multifaceted changes to sleep from juvenile to mature adulthood. Here, we use a non-invasive probabilistic approach to investigate the changes in sleep architecture in juvenile and mature flies. Increased sleep in juvenile flies is driven primarily by a decreased probability of transitioning to wake and characterized by more time in deeper sleep states. Functional manipulations of sleep-promoting neurons in the dorsal fan-shaped body (dFB) suggest that these neurons differentially regulate sleep in juvenile and mature flies. Transcriptomic analysis of dFB neurons at different ages and a subsequent RNAi screen implicate the genes involved in dFB sleep circuit maturation. These results reveal that the dynamic transcriptional states of sleep output neurons contribute to the changes in sleep across the lifespan.


Citridones, new potentiators of antifungal miconazole activity, produced by Penicillium sp. FKI-1938. II. Structure elucidation.
The structures of citridones A, B, B' and C, new potentiators of miconazole activity against Candida albicans produced by Penicillium sp. FKI-1938, were elucidated by various spectroscopic analyses including UV, NMR, and MS and degradation experiments. Although citridones B and B' were isolated as a mixture, each structure was also elucidated, indicating that they exist in equilibrium of hemiacetal epimerization. Citridones A, B and B' have a similar phenylfuropyridone moiety.


Low re-excision rate for positive margins in patients treated with ultrasound-guided breast-conserving surgery.
Re-excision is a necessary procedure in obtaining clean margins for breast-conserving surgery (BCS)-treated patients. Re-excision rates vary widely among different breast cancer management procedures. The aim of this study was to evaluate the efficacy of ultrasound (US)-guided BCS to decrease the re-excision rate in patients with US-detectable breast cancer, as well as the relationship between positive margins and ultrasonographic characteristics of tumor. Between 2008 and 2009, we identified consecutive patients who underwent initial US-guided BCS for breast in situ or invasive carcinoma, which was preoperatively detected using US examination and on the basis of image-guided biopsy findings. The margins achieved after BCS were separately assessed by performing frozen section analysis of shaved margins. The negative margin and positive margin groups were compared for clinicopathological features and ultrasonographic findings. Of 381 patients undergoing US-guided BCS, 126 (33.1%) had palpable tumors and 255 (66.9%) had nonpalpable tumors. Positive margins were noted in 35 patients (9.2%). These patients underwent re-excision and were margin-free; no further surgery was required for these patients. There were no significant intergroup differences in clinicopathological features and ultrasonographic findings. Breast US is an effective modality for intraoperative tumor localization and can thus help obtain clean margins and reduce the re-excision rate in cases in which breast-conserving therapy has been performed. Furthermore, frozen section analysis of cavity shaved margins is a feasible method for minimizing the need for further surgery.


Retrospective study of the prevalence and characteristics of adverse drug events in adults who present to an Australian emergency department.
To determine the burden, on the ED, of harm from unintentional adverse drug events (ADEs) in the community. A retrospective, observational study of 936 randomly selected presentations to a level 6 ED at a principal referral hospital in Brisbane, Australia, in November 2017. Clinical records were screened by a pharmacist, who identified suspected ADEs. All suspected ADEs and a random selection of presentations without ADEs were reviewed by an expert panel, which classified, by consensus: occurrence and type of ADE, contribution of ADE to presentation, severity of harm and preventability of presentation. Medication-related ED presentations (ADE-Ps) and potential ADEs were, respectively, defined as presentations directly attributable to an ADE, and medication events that occurred but did not cause the ED presentation. Descriptive data analysis was performed. The median (interquartile range) age of patients was 40 (27-58) years, with 49.7% (95% confidence interval [CI] 46.5-52.9) being male. The prevalences of ADE-Ps and potential ADEs were 9.2% (95% CI 7.5-11.3) and 5.0% (95% CI 3.8-6.6), respectively. The severity of harm was classified as 'death or likely permanent harm' in 4.7% (95% CI 0.2-9.1) of ADE-Ps, 'temporary harm' (89.5%, 95% CI 83.1-96.0) and 'minimal or no harm' (5.8%, 95% CI 0.9-10.8). Most (79.1%, 95% CI 70.5-87.7) ADE-Ps were preventable. There is a high burden on emergency care because of unintended medication harm in the community. Interventions to reduce such harm are likely to require a co-ordinated primary, acute and public healthcare response. The high proportion of presentations with potential ADEs indicates opportunity for harm mitigation in the ED.


A computerized aid to support smoking cessation treatment for hospital patients.
Hospital-based interventions promote smoking cessation after discharge. Strategies to deliver these interventions are needed, especially now that providing smoking cessation advice or treatment, or both, to inpatient smokers is a publicly reported quality-of-care measure for US hospitals. To assess the effect of adding a tobacco order set to an existing computerized order-entry system used to admit Medicine patients to 1 hospital. Pre-post study. Proportion of admitted patients who had smoking status identified, a smoking counselor consulted, or nicotine replacement therapy (NRT) ordered during 4 months before and after the change. In 4 months after implementation, the order set was used with 76% of Medicine admissions, and a known smoking status was recorded for 81% of these patients. The intervention increased the proportion of admitted patients who were referred for smoking counseling (0.8 to 2.1%) and had NRT ordered (1.6 to 2.5%) (p < .0001 for both). Concomitantly, the hospital's performance on the smoking cessation quality measure improved. Adding a brief tobacco order set to an existing computerized order-entry system increased a hospital's provision of evidence-based tobacco treatment and helped to improve its performance on a publicly reported quality measure. It provides a model for US hospitals seeking to improve their quality of care for inpatients.


Comparison of the enthalpy recovery and free volume of polyvinylpyrrolidone during anomalous glassy to rubbery transition.
Previous studies confirmed that along with the structural changes of the amorphous binder, that of the polyvinylpyrrolidone, the tensile strength and consequently, the dissolution behaviour of its tablets changed significantly during the storage period. Structural formation during the glassy to rubbery transition of polyvinylpyrrolidone was followed by the changes in the free volume and enthalpy recovery values of the polymer. The results suggest that the apparent structure formation of water and polymer under glassy to rubbery transition is interrelated in a dynamic and complex manner which can be tracked by the combination of enthalpy recovery studies and positron lifetime measurements. Positron lifetime measurements more sensitively react to the structural rearrangements than enthalpy recovery, thus it can be recommended as a sensitive tool for stability tests during the formulation phase of drug development.


Time-dependent effects of ATP and its degradation products on inflammatory markers in human blood ex vivo.
We recently reported that adenosine 5'-triphosphate (ATP) modulates cytokine release in lipopolysaccharide (LPS)-phytohemagglutinin (PHA)-stimulated blood. ATP inhibited tumor necrosis factor-alpha (TNF-alpha) release via activation of the P2Y(11) receptor and increased interleukin (IL)-10 release via stimulation of the P2Y(12) receptor. Because ATP is known to be broken down by various ecto-enzymes, we determined the degradation profile of ATP in time in LPS-PHA-stimulated blood. ATP slowly metabolized with 14% remaining after 6h. Simultaneously, adenosine 5'-diphosphate (ADP), adenosine 5'-monophosphate (AMP) and hypoxanthine were formed. Subsequently, we investigated the time-dependent effects of ATP and its metabolites on inflammatory markers. Results showed that ATP decreased the rise in concentrations of TNF-alpha, interferon-gamma (IFN-gamma) and IL-1beta, but increased concentrations of IL-8 and IL-10. Metabolites of ATP showed either no, similar or opposite effects on cytokine release, compared to ATP. In conclusion, ATP has rapid immunomodulatory effects on a variety of cytokines in stimulated whole blood that persist until 24h.


Prospective anatomical study to determine the site of insertion of recurrent laryngeal nerve into the larynx.
Determine whether the insertion site of the recurrent laryngeal nerve (RLN) occurs at a predictable distance from the midline trachea, to help guide safe dissection during thyroid surgery. Prospective clinical trial. At the inferior edge of the cricoid cartilage, we measured the distance from mildline trachea to the RLN insertion site. Single institution. 50 consecutive patients undergoing thyroid surgery. Distance from midline trachea to laryngeal insertion of RLN. The study population included 36 women and 14 men, with 72 total nerves measured. The average distance-to-midline + standard deviation (range) of the RLN was 20.7 + 2.3 (17-26) mm in women compared to 26.3 + 2.1 (22-32) mm in men. The insertion point of the RLN into the larynx at the level of inferior border of the cricoid cartilage can be reliably predicted, to facilitate early identification of the RLN during thyroid surgery.


Pharmacological inhibition of cyclin dependent kinases causes p53 dependent apoptosis in renal cell carcinoma.
We evaluated the effect of roscovitine (Sigma-Aldrich®), a pharmacological inhibitor of cyclin dependent kinase, on renal cell carcinoma cell lines in vitro. We exposed several renal cell carcinoma cell lines to roscovitine and examined apoptotic signaling pathways using immunoblotting and immunohistochemistry. As expected, roscovitine caused dose and time dependent inhibition of cyclin dependent kinase 2 autophosphorylation, and of cyclin dependent kinase mediated Pol II phosphorylation in the ACHN (p53-wt) and 786-O (p53 inactive) renal cell carcinoma cell lines (ATCC®). Roscovitine also induced apoptosis in each cell line within a narrow concentration range (about 10 μg/ml). Apoptosis induction was more efficient in ACHN than in 786-O cells and at least partly due to p53 activity. In ACHN cells roscovitine induced apoptosis was associated with p21 induction, and decreased Akt1, XIAP and phospho-Rb expression. These changes also depended on p53 and were not present (p21) or showed a different dose pattern (Akt1, XIAP and phospho-Rb) in 786-O cells. Partial restoration of roscovitine induced apoptosis in 786-O cells by the Mdm-2 inhibitor nutlin-3 (Sigma-Aldrich) suggests that the inactivating mutation of VHL in these cells and its destabilizing effect on p53 are responsible for the decreased sensitivity to apoptosis. Our data extend previous studies documenting the pro-apoptotic effect of roscovitine and to our knowledge show for the first time that this activity is restricted to a narrow dose range in renal cell carcinoma cells and partly depends on p53. Thus, roscovitine is a novel potential chemotherapy in a subset of patients with renal cell carcinoma if a narrow therapeutic window is used. These data also provide insight into the role of VHL mutation and p53 in the renal cell carcinoma response to therapeutic cyclin dependent kinase manipulation.


[Power station sun and hormone factory skin : A current assessment of the importance of vitamin D metabolism during human evolution and strategies for UV prevention].
The sun is of great importance for human health. One important reason for this is the production of vitamin D, endorphins and many other hormones by the skin due to stimulation by sunlight. Insufficient access to sunlight increases the risk for vitamin D deficiency, a pandemic which would affect more than one billion people worldwide and under which ca. 60% of the population in Germany would suffer. The skin has a unique position in vitamin D metabolism as elementary steps for vitamin D production take place here and it is furthermore a target organ for actions of vitamin D. Due to the many positive effects of the sun, a healthy balance must be found between UV protection to shield against skin cancer but also ensuring sufficient vitamin D production. For regulation of this fragile balance between photoprotection and vitamin D production, which has accompanied mankind throughout evolution, sunscreens are an integral part of the modern lifestyle, although critical reports on possible risks for their use have recently become more frequent. This article discusses the current state of knowledge on the importance of vitamin D metabolism in human skin and the use of sun creams.


T-cell activation: interplay at the interface.
Recent studies have shown that, when a T cell interacts with a cognate antigen-presenting cell, an organized adhesive contact is formed between the two cells by a process which involves the dynamic, three-dimensional redistribution of entire signaling assemblies.


Competitive virus and host RNAs: the interplay of a hidden virus and host interaction.
During virus infection, viral RNAs and mRNAs function as blueprints for viral protein synthesis and possibly as pathogen-associated molecular patterns (PAMPs) in innate immunity. Here, considering recent research progress in microRNAs (miRNAs) and competitive endogenous RNAs (ceRNAs), we speculate that viral RNAs act as sponges and can sequester endogenous miRNAs within infected cells, thus cross-regulating the stability and translational efficiency of host mRNAs with shared miRNA response elements. This cross-talk and these reciprocal interactions between viral RNAs and host mRNAs are termed "competitive viral and host RNAs" (cvhRNAs). We further provide recent experimental evidence for the existence of cvhRNAs networks in hepatitis B virus (HBV), as well as Herpesvirus saimiri (HVS), lytic murine cytomegalovirus (MCMV) and human cytomegalovirus (HCMV) infections. In addition, the cvhRNA hypothesis also predicts possible cross-regulation between host and other viruses, such as hepatitis C virus (HCV), HIV, influenza virus, human papillomaviruses (HPV). Since the interaction between miRNAs and viral RNAs also inevitably leads to repression of viral RNA function, we speculate that virus may evolve either to employ cvhRNA networks or to avoid miRNA targeting for optimal fitness within the host. CvhRNA networks may therefore play a fundamental role in the regulation of viral replication, infection establishment, and viral pathogenesis.


Bloom syndrome B-lymphoblastoid cells are hypersensitive towards carcinogen and tumor promoter-induced chromosomal alterations and growth in agar.
The effects of the carcinogens (4NQO, 4-nitroquinoline-N-oxide; MNNG, N-methyl-N'-nitro-N-nitrosoguanidine; AFLG1, aflatoxin G1; AFLB1, aflatoxin B1; BNU, butylnitrosourea; MNU, methylnitrosourea) and the tumor promoter (TPA, 12-O-tetradecanoylphorbol-13-acetate) on sister chromatid exchanges (SCE), chromosome aberrations and colony formation (CF) were examined in three types of Bloom syndrome (BS) B-lymphoblastoid cell lines (B-LCLs); type I with normal SCE and normal karyotype; type II with high SCE and normal karyotypes; type III with high SCE and abnormal karyotypes. BS type I cells had the same SCE and CF response as normal cells to these carcinogens and TPA. In BS type II and III cells treated with carcinogens the SCE frequency increased to 140/cell from a baseline of 70/cell versus an increase of only 10/cell in normal cells. Colony formation occurred at the concentrations that caused the highest SCE. TPA caused a significant SCE increase and highly enhanced CF with dose dependency only in type III cells, suggesting that type III cells may be already in a pre-malignant state; type II cells appear to be one step behind those of type III in the process of becoming malignant. BS type II and III cells may be usable to establish a sensitive system to detect SCE-inducing agents.


Exploring isotropic tendency for the blue membrane containing wild-type bacteriorhodopsin.
Bacteriorhodopsin of purple membrane has wide potential applications in bioelectronics and biophotonic nanodevices. Upon acidification, it turns blue and upon further acidification by HCl, it retains its purple color. The acid-induced structural changes might be correlated to its crystalline structure, which might be mediated by lipids of purple membrane. Therefore, the present study aims at revealing the acidic pH dependence of anisotropic properties of bacteriorhodopsin. The electric impedance has been measured for parallel- and perpendicular-oriented purple membrane, in addition to the randomly-oriented one in the acidic pH range. The results have showed that the electric anisotropy is proportional to the color transitions occurred at low pH with consistent pKa values. It has found that the bacteriorhodopsin, upon turning into blue form, tends to be isotropic within narrow pH region around 2.55, whereas it preserves its anisotropy in its purple form. It is noteworthy that several mutants of bacteriorhodopsin that resemble its blue form became attractive in technical applications such as real-time holographic interferometry and optical data storage. Accordingly, such isotropic tendency might implicate bacteriorhodopsin for further potential technical applications.


[Clinical effect of functional chewing training in treatment of oral motor dysfunction in children with cerebral palsy: a prospective randomized controlled clinical trial].
To study the effect of functional chewing training (FuCT) on masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy. A prospective study was performed for 48 children who were diagnosed with oral motor dysfunction from January 2019 to January 2020, and they were randomly divided into an FuCT group and an oral motor training group, with 24 children in each group. Both groups received FuCT or oral motor training for 12 weeks, and then they were evaluated in terms of the changes in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling. There were no significant differences between the two groups in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling before treatment (P>0.05). After the 12-week training, the FuCT group showed significant improvements in the masticatory function and the severity of tongue thrust and drooling (P<0.05), but with no improvement in the frequency of drooling (P>0.05), while the oral motor training group had no improvements in the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling (P>0.05). After the 12-week training, the FuCT group had more significantly improvements in the severity of tongue thrust and the severity and frequency of drooling than the oral motor training group (P<0.05). FuCT can effectively improve the masticatory function, the severity of tongue thrust, and the severity and frequency of drooling in children with cerebral palsy.


Effects of out-of-hours and winter admissions and number of patients per unit on mortality in pediatric intensive care.
To investigate the effect of out-of-hours and winter admissions, and unit size on risk adjusted mortality in pediatric intensive care. A national pediatric intensive care clinical audit provided data on over 86000 admissions to 29 pediatric intensive care units (2006-2011). Multivariate logistic regression modeled risk adjusted mortality prior to discharge with out-of-hours (night, weekend, public holiday) admissions, admissions per unit, winter admission, and potential confounders, overall and separately for emergency and planned admissions. Nearly one-half (47.1%) of admissions were out-of-hours (n = 40948) and 79.2% of those were emergencies. Mortality for all out-of-hours admissions was raised (OR 1.1; 95% CI 1.02-1.2; P = .013), accounted for by planned admissions (OR 1.99; 95% CI 1.67-2.37; P < .001) compared with a reduced risk for emergency admissions (OR 0.93; 95% CI 0.86-1.1; P = .07). Winter admissions were associated with increased risk. Unit size did not affect mortality. A child admitted to pediatric intensive care as an out-of-hours emergency is not at increased risk of dying compared with a weekday daytime admission, indicating pediatric intensive care units provide consistent quality of care around the clock. Excess mortality in planned out-of-hours admissions may be explained by admissions following complex operations where risk-adjustment models underestimate the true probability of mortality. In winter, a time of seasonally high bed occupancy, there was an increased mortality risk, an effect which requires further investigation. Despite the different characteristics of small units, the absence of any effect of unit size on mortality suggests that number of admissions per unit does not influence standards of care.


New strategies in allogeneic stem cell transplantation: immunotherapy using irradiated allogeneic T cells.
Recipients of T cell-depleted allogeneic bone marrow transplants have increased risks of relapse and graft rejection. The addition of donor T cells to the TCD allograft will decrease the risk of graft rejection but will increase the risk of graft-versus-host disease (GVHD). Relapse of leukemia or lymphoma following allogeneic bone marrow transplantation can be successfully treated with post-transplant infusions of donor lymphocytes. A relatively small number of donor T cells can have a profound anti-tumor effect and facilitate engraftment, but has an unpredictable potential for severe GVHD. An alternative to using viable immunocompetent donor immune cells to facilitate engraftment and to treat relapsed patients are donor lymphocytes that have been treated to limit their ability to proliferate and cause GVHD. T cells treated with irradiation retain cytotoxic activity against tumor cells and host immune cells. We have tested the hypothesis that allogeneic donor T cells treated with low-dose irradiation will facilitate engraftment and mediate an anti-leukemia effect in a mouse model of bone marrow transplantation. Multiple infusions of irradiated allogeneic donor lymphocytes in the peri-transplant period had graft-enhancing activity without resulting in GVHD. Murine recipients of irradiated allogeneic splenocytes and allogeneic bone marrow had stable donor-derived hematopoiesis without a significant contribution of irradiated donor cells to the T cell compartment. Removing T cells from the allogeneic splenocytes prior to irradiation largely eliminated their graft facilitating activity. Based upon the promising results of the pre-clinical murine studies, we initiated a phase I clinical trial of multiple infusions of irradiated allogeneic lymphocytes in patients who had relapsed after allogeneic BMT. Of 12 patients treated to date on this study, three have shown objective responses of their leukemia or lymphoma to multiple infusions of irradiated donor lymphocytes. We have initiated a new phase I clinical study to test the efficacy of multiple infusions of irradiated allogeneic cytotoxic T cells to facilitate engraftment in allogeneic transplantation. Successive cohorts of patients will be transplanted with allogeneic stem cells alone, or a combination of allogeneic stem cells and increasing numbers of irradiated allogeneic T cells. Irradiated allogeneic lymphocytes that retain short-term allo-specific cytotoxicity and lack the potential for clonal expansion in vivo can be considered as a novel form of immunotherapy with defined pharmacokinetics.


Total length of positive resection margins can predict remnant gastric cancer following endoscopic submucosal dissection.
Prediction of remnant tumor is important in determining subsequent treatment options for gastric cancer patients with positive resection margin (RM) after endoscopic submucosal dissection (ESD). Based on the assumption that pathologic factors, including the length and type of involved RM, could potentially predict residual tumor, we evaluated 451 ESD specimens in patients with early gastric cancer. Of 408 cases, 37 (9.1 %) showed positive RMs. RM involvement in gastric cancer ESD specimens was associated with extended or beyond ESD criteria, greater tumor size, poor differentiation, submucosal invasion, lymphovascular invasion, and upper third location. Among the 37 positive RM cases, residual tumor was present in seven (18.9 %). The presence of residual tumor was not significantly associated with any clinicopathologic parameters except for tumor size and RM status. The total length of the involved RM was the most significant factor associated with the presence of residual tumor (P < 0.008). A total length cut-off value of 6 mm yielded a sensitivity of 85.7 % and negative predictive value of 94.7 % for predicting remnant tumor at gastrectomy following ESD. In conclusion, when the ESD specimen exhibits positive RM, a quantitative assessment of the involved RM should be included in the pathology report, as this can help the clinician predict remnant tumor and determine appropriate future treatment.


Social determinants of health and CDK4/6 inhibitor use and outcomes among patients with metastatic breast cancer.
Survival outcomes in metastatic breast cancer (MBC) have improved due to novel agents such as CDK4/6 inhibitors (CDK4/6i). Nevertheless, Black patients and patients with lower socioeconomic status (SES) continue to bear a disproportionate mortality burden. We conducted a retrospective analysis of EHR-derived data from the Flatiron Health Database (FHD). A dataset was constructed to include Black/African-American (Black/AA) and White patients with hormone receptor (HR)-positive, HER2-negative MBC. Outcomes included CDK4/6i use (overall and first-line), and rates of leukopenia, dose reduction, and time on treatment for first-line CDK4/6i. Multivariable logistic regression was used to evaluate factors associated with use and outcomes. A total of 6802 patients with MBC were included, of which 5187 (76.3%) received CDK4/6i. Of those, 3186 (61.4%) received CDK4/6i first-line. Overall, 86.7% of patients were categorized as White and 13.3% as Black/AA; 22.4% were > 75 years old; 12.6% were treated at an academic site; 3.3% had Medicaid insurance. In addition to advanced age and poorer performance status, lower use of CDK4/6i was associated with Black/AA vs White race (72.9% vs 76.8%; OR 0.83, 95% CI 0.70-0.99, p = 0.04) and Medicaid vs commercial insurance (69.6% vs 77.4%; OR: 0.68, 95% CI 0.49-0.95, p = 0.02). Odds of CDK4/6i use were twofold higher for patients treated at an academic center (p < 0.001). Rates of CDK4/6i-induced leukopenia and dose reductions did not differ significantly by race, insurance type, or treatment site. Time on CDK4/6i was significantly lower among Medicaid patients (395 days) than patients with commercial insurance (558 days) or Medicare (643 days) (p = 0.03). This analysis of real-world data suggests that Black race and lower SES are associated with decreased CDK4/6i use. However, among patients treated with CDK4/6i, subsequent toxicity outcomes are similar. Efforts to ensure access to these life-prolonging medications are warranted.


Guidance of intracoronary radiation therapy based on dose-volume histograms derived from quantitative intravascular ultrasound.
Application of ionizing radiation to prevent restenosis in atherosclerotic vessels treated by balloon angioplasty is a new treatment under investigation in interventional cardiology and radiology. There is variability in dose prescription, and both gamma- and beta-emitters are used, leading to a wide range of dose distribution over the arterial vessel wall. We present a new modality of dosimetry based on a method that three-dimensional (3-D) image reconstruction of electrocardiogram (ECG)-gated intravascular ultrasound (IVUS) images. Dose volume histograms (DVH) are used to describe the cumulative distribution of dose over two specific volumes: i) at the level of the luminal surface, defined with a thickness of 0.1 mm from the automatically detected contour of the highly echogenic blood-vessel interface, and ii) the adventitia volume is computed considering a 0.5-mm thickness from the echogenic media-adventitia interface. DVH provide a tool for reporting the actual delivered dose at the site believed to be the target: the adventitia, and to detect excessive radiation which could lead to vascular complications. Simulation of a gamma-emitter or of a radioactive source train in the center of the lumen are possible. The data obtained from the first ten patients included in the beta-irradiation trial (BERT 1.5) conducted in our institution are presented, supporting the use of DVH based on quantitative IVUS measurements for optimal dose prescription in vascular interventional radiation therapy.


A large tuberculosis abscess causing spinal cord compression of the cervico-thoracic region in a young child.
Despite numerous descriptive publications, the guidelines for treatment of cervical spinal tuberculosis (TB) are not very clear. The authors report a case of a young girl with cervico-thoracic spinal TB extending from C5 to T3 vertebrae presenting with weakness of the right hand and unsteady gait. An 11-year-old female who is an immigrant to the UK from Afghanistan, presented to our clinic with a 10-day history of difficulty in walking with an unsteady gait and 3-month history of progressive weakness in both her arms, the right side more affected than the left. Her immunisation history was unclear. Examination of the arms showed bilateral thenar and hypothenar wasting, more so on the right than the left. An MRI scan revealed a large para-spinal abscess extending from C3/4 to T4/5 with a significant anterior epidural cord compression from C5/6 to T2/3. Therapeutic/diagnostic aspiration was performed under ultrasound guidance and the aspirate was sent for microbiology. She was started empirically on multidrug anti-tubercular treatment and steroids. Although Ziehl-Neelsen stain was negative for acid-fast bacilli, microbiological confirmation of TB was obtained by positive TB culture sensitive to all first-line anti-TB drugs. She made a dramatic improvement within 3 weeks of anti-tubercular treatment. A follow-up MRI scan at 8 months showed complete resolution of the abscess. At 2 years of follow-up, she was a healthy looking child, back to her school with no residual clinical signs/symptoms of the disease. Our case of cervico-thoracic tuberculous abscess in a young child suggests that even with incomplete neurological deficit caused by epidural cord compression, ultrasound (or CT)-guided aspiration and anti-tubercular medication provide acceptable results at 2 years of follow-up.


Interplay between hepatic mitochondria-associated membranes, lipid metabolism and caveolin-1 in mice.
The mitochondria-associated membrane (MAM) is a specialized subdomain of the endoplasmic reticulum (ER) which acts as an intracellular signaling hub. MAM dysfunction has been related to liver disease. We report a high-throughput mass spectrometry-based proteomics characterization of MAMs from mouse liver, which portrays them as an extremely complex compartment involved in different metabolic processes, including steroid metabolism. Interestingly, we identified caveolin-1 (CAV1) as an integral component of hepatic MAMs, which determine the relative cholesterol content of these ER subdomains. Finally, a detailed comparative proteomics analysis between MAMs from wild type and CAV1-deficient mice suggests that functional CAV1 contributes to the recruitment and regulation of intracellular steroid and lipoprotein metabolism-related processes accrued at MAMs. The potential impact of these novel aspects of CAV1 biology on global cell homeostasis and disease is discussed.


Association of postprandial postexercise muscle protein synthesis rates with dietary leucine: A systematic review.
Dietary protein ingestion augments post (resistance) exercise muscle protein synthesis (MPS) rates. It is thought that the dose of leucine ingested within the protein (leucine threshold hypothesis) and the subsequent plasma leucine variables (leucine trigger hypothesis; peak magnitude, rate of rise, and total availability) determine the magnitude of the postprandial postexercise MPS response. A quantitative systematic review was performed extracting data from studies that recruited healthy adults, applied a bout of resistance exercise, ingested a bolus of protein within an hour of exercise, and measured plasma leucine concentrations and MPS rates (delta change from basal). Ingested leucine dose was associated with the magnitude of the MPS response in older, but not younger, adults over acute (0-2 h, r2 = 0.64, p = 0.02) and the entire postprandial (>2 h, r2 = 0.18, p = 0.01) period. However, no single plasma leucine variable possessed substantial predictive capacity over the magnitude of MPS rates in younger or older adults. Our data provide support that leucine dose provides predictive capacity over postprandial postexercise MPS responses in older adults. However, no threshold in older adults and no plasma leucine variable was correlated with the magnitude of the postexercise anabolic response.


Survival of developing dopaminergic neurons in reaggregate tissue culture following treatment with methamphetamine.
Developing central dopamine (DA)-containing neurons in rotation-mediated reaggregate tissue culture exposed to 10(-4) M methamphetamine for 1 week (at a time corresponding to the 2nd week of postnatal development) exhibit decreased DA levels. DA neurons were visualized either by a histofluorescent method after 'loading' with exogenous DA, or by tyrosine hydroxylase (TH) immunocytochemistry. An apparent loss of histofluorescent DA cell bodies was observed due to a methamphetamine-induced reduction in exogenous DA accumulation. No decrease in the number of TH-immunoreactive neurons was observed. Thus, developing DA neurons when visualized by TH immunocytochemistry survive despite methamphetamine-induced reductions in DA levels.


Construction and validity of the Interprofessional Communication in Health Scale.
to construct and validate the Interprofessional Communication Scale in Health. a psychometric study was carried out on a sample of 360 nurses from a hospital and university center in central Portugal. Reliability was assessed through internal consistency and construct validity through exploratory and confirmatory factor analysis. the Interprofessional Communication in Health Scale, consisting of 27 items, is organized into 3 factors: "Teamwork", "Conflict management" and "Leadership", with a total variance of 51.1%. Good internal consistency was obtained, with a Cronbach's alpha of 0.842, and adequate Goodness of Fit Index model. the Interprofessional Communication in Health Scale presents a factorial structure with adequate validity and reliability results, and may constitute a useful self-report instrument in assessing interprofessional communication in health.


Combination of Zetaprep mass ion-exchange media and high-performance cation-exchange chromatography for the purification of high-purity monoclonal antibodies.
A procedure involving diafiltration, mass ion exchange on a QAE Zetaprep disk, gel chromatography and cation-exchange chromatography was used for the purification of mouse monoclonal antibodies from hybridoma culture supernatant. Prior to the separation steps, the starting solution was adjusted to the desired pH and conductivity. Diafiltration was used for this purpose in order to keep the volume constant or even to reduce the volume of sample. A QAE Zetaprep disk was used to remove the main protein contaminants from the culture supernatant. After washing unbound proteins out of the Zetaprep disk, slightly bound protein was eluted with a buffer solution containing 50 mM sodium chloride. The monoclonal antibody was eluted with a solution containing 150 mM sodium chloride. The purity of the eluted antibody was 50%, and was increased to 99% by subsequent high-performance cat-ion-exchange chromatography. The purity was determined by means of sodium-dodecyl sulphate polyacrylamide gel electrophoresis and silver staining. The advantage of the two high-performance techniques, mass ion exchange and high-performance cation-exchange chromatography, are the high-flow-rates and the high resolution that can be obtained. These techniques are suitable for the production of injectable therapeutic preparations.


Effect of 1,1'-(2,2,2-trichloroethylidene)-bis(4-chlorobenzene) (DDT) on gap junctional intercellular communication and morphological transformation of Syrian hamster embryo cells.
The organochlorine insecticide 1,1'-(2,2,2-trichloroethylidene)bis(4-chlorobenzene) (DDT) did not induce or promote induction of morphological transformation in Syrian hamster embryo (SHE) cells, but it was a potent inhibitor of gap junctional intercellular communication (GJIC). The kinase inhibitor staurosporine did not affect DDT induced inhibition of GJIC, although it has been shown to decrease the inhibitory effect of 12-O-tetradecanoyl-phorbol-13-acetate (TPA) on GJIC. In addition, pretreatment with TPA made the cells refractory to further TPA induced inhibition of GJIC, while they remained sensitive to DDT. Thus, DDT and TPA inhibit GJIC through different mechanisms. Elevation of cellular cyclic adenosine monophosphate (cAMP) level by exposure to forskolin counteracted the inhibitory effect of DDT similar to that observed for TPA. Continuous exposure to DDT at concentrations near the effective concentration (50%) value (EC50 value) resulted in a slight recovery of GJIC following the initial inhibition. This recovery was not accompanied by the cells becoming refractory to further DDT induced inhibition of GJIC. The recovery of GJIC after removal of the DDT containing medium seemed to be related to a reduction in the amount of cell-associated DDT.


The spectrum of disorders presenting as adult-onset focal lower extremity dystonia.
Uncommonly, adult-onset dystonia is confined to one lower extremity. We sought to characterize the clinical spectrum associated with the presenting phenotype of lower limb dystonia including foot torsion. Retrospective computer search of the Mayo Clinic Medical Records Linkage System (1996-2006). Inclusion criteria were (1) a principal, initial diagnosis of monomelic lower extremity dystonia with foot torsion; (2) no neurologic findings outside of the affected limb; (3) age-onset>18 years. Prospective data were sought from apparent idiopathic cases. We identified 36 patients (31 females) presenting with monomelic lower limb dystonia including foot torsion. Onset was usually subacute or insidious (32 patients); mean symptom duration was 28.8 months (range, 1-96), age-onset 47.5 years (range, 21-77). After a mean follow-up of 3.1 years, causes were identified in over half, including 5 with parkinsonism. Other treatable etiologies included psychogenic dystonia (3 patients) and stiff-limb syndrome (2 patients). Post-traumatic dystonia was diagnosed in 10 patients and consistently manifested as fixed, painful foot torsion, in contrast to the action-induced dystonia in 5 parkinsonism cases, and 10 of 14 patients with primary lower limb dystonia. Imaging identified the cause in only 1 patient (ischemic stroke) and was negative in the single patient with pyramidal signs. Adults presenting with monomelic lower limb dystonia with foot torsion often have an identifiable cause, sometimes treatable, including Parkinson's disease (diagnosed with levodopa trial) or immune-mediated stiff-limb syndrome. Post-traumatic dystonia was the single most frequent cause and proved difficult to treat. Unlike certain other series of such patients, psychogenic dystonia was an uncommon clinical diagnosis.


Lateral pharyngotomy approach in the treatment of oropharyngeal carcinoma.
Surgery for early-intermediate oropharyngeal squamous cell carcinoma (OPSCC) may involve using transoral endoscopic approaches or open surgical procedures. "Lateral pharyngotomy" (LP) is an open surgical approach that improves exposure of the oropharyngeal region, while avoiding mandibulotomy. The aim of the present study was to retrospectively analyze our experience with the surgical treatment of early-intermediate OPSCC using the LP approach, and to investigate the potentially prognostic clinical and/or pathological factors that might identify patients at higher risk of recurrence after primary surgery. Sixty-four patients with previously untreated early-intermediate (pT1-T2-T3) OPSCC consecutively underwent partial pharyngectomy using a LP approach, performed by the same surgical team at a tertiary head and neck oncology center (Otolaryngology Unit, Vittorio Veneto Hospital, Italy). The 2-year disease-specific survival rates were 86% for stage I-II and 77% for stage III-IV disease. All patients who experienced locoregional or distant metastases died of their disease, while no patients died of any complications of the treatment. Postoperative complications occurred in 25 patients (39%), the most common being pharyngocutaneous fistula. All but one of the patients experienced a complete recovery of oral food intake. In conclusion, the LP approach to oropharyngeal cancer could be a valid open surgical alternative to oropharyngectomy with mandibulotomy for: (a) patients with early-intermediate OPSCC in whom oropharyngeal exposure proves difficult, and/or who are not eligible for transoral endoscopic surgery; (b) HPV-negative OPSCCs; and


Sphingomyelinase enzyme assay in Niemann-Pick disease.
Niemann-Pick group of diseases are rare autosomal recessive disorders of lysosomal enzymes. These are divisible into six types depending on clinical and biochemical features. On the basis of sphingomyelinase assay in five cases of Niemann-Pick disease, three cases were classified as type IA, one as type IS and one as type IIS. Their clinicopathological profiles are compared with 17 cases reported previously from India.


The impact of welfare reform on the health insurance coverage, utilization and health of low education single mothers.
The Personal Responsibility Work Opportunity and Reconciliation Act (PRWORA) of 1996 imposed time limits on the receipt of welfare cash benefits and mandated cash benefit sanctions for failure to meet work requirements. Many studies examining the health implications of PRWORA have found associated declines in health insurance coverage and healthcare utilization among single mothers but no impact of PRWORA on health outcomes. A limitation of this literature is that most studies cover a time period before time limits were implemented in all states and also before individuals began actually timing out. This work builds on previous studies by exploring this research question using data from the Survey of Income and Program Participation that covers a time period after all states have implemented time limits (1991-2009). We use a difference-in-differences study design that exploits variability in eligibility for cash welfare benefits by marital status and state-level variation in timing of PRWORA implementation to identify the effect of PRWORA. Using ordinary least square regression models, controlling for state-level and federal policies, individual-level demographics and state and year fixed-effects, we find that PRWORA leads to 7 and 5 percentage point increases in self-reported poor health and self-reported disability among white single mothers without a diploma, respectively.


Ferric haem forms of Mycobacterium tuberculosis catalase-peroxidase probed by EPR spectroscopy: Their stability and interplay with pH.
Low temperature EPR spectroscopy was used to characterise Mycobacterium tuberculosis catalase-peroxidase in its resting ferric haem state. Several high spin ferric haem forms and no low spin forms were found in the enzyme samples frozen in methanol on dry ice. The EPR spectra depended not only on the pH but also on the buffer type. As a general trend, the higher the pH, the greater the 'rhombic' fraction of the high spin ferric haem that was observed. The rhombic form was characterised by well separated two lines in the g = 6 region whereas in the 'axial' form the two lines overlap. This pH dependence of the equilibrium of axial and rhombic ferric haem forms is also seen in rapidly freeze-quenched samples. Different high spin ferric haem forms were monitored during a 3 week storage of the enzyme at 4 °C. For some forms, extremal dependences, i.e. those progressing via maxima or minima over storage time, were found. This indicates that the mechanism of the time-dependent transition from one high spin ferric haem form to another must be more complex than a simple single site oxidation.


Effects of Hyperbaric Oxygen Intervention on the Degenerated Intervertebral Disc: From Molecular Mechanisms to Animal Models.
MicroRNA (miRNA) 107 expression is downregulated but Wnt3a protein and β-catenin are upregulated in degenerated intervertebral disc (IVD). We investigated mir-107/Wnt3a-β-catenin signaling in vitro and in vivo following hyperbaric oxygen (HBO) intervention. Our results showed 96 miRNAs were upregulated and 66 downregulated in degenerated nucleus pulposus cells (NPCs) following HBO treatment. The 3' untranslated region (UTR) of the Wnt3a mRNA contained the "seed-matched-sequence" for miR-107. MiR-107 was upregulated and a marked suppression of Wnt3a was observed simultaneously in degenerated NPCs following HBO intervention. Knockdown of miR-107 upregulated Wnt3a expression in hyperoxic cells. HBO downregulated the protein expression of Wnt3a, phosphorylated LRP6, and cyclin D1. There was decreased TOP flash activity following HBO intervention, whereas the FOP flash activity was not affected. HBO decreased the nuclear translocation of β-catenin and decreased the secretion of MMP-3 and -9 in degenerated NPCs. Moreover, rabbit serum KS levels and the stained area for Wnt3a and β-catenin in repaired cartilage tended to be lower in the HBO group. We observed that HBO inhibits Wnt3a/β-catenin signaling-related pathways by upregulating miR-107 expression in degenerated NPCs. HBO may play a protective role against IVD degeneration and could be used as a future therapeutic treatment.


Dissociation of ERMES clusters plays a key role in attenuating the endoplasmic reticulum stress.
In yeast, ERMES, which mediates phospholipid transport between the ER and mitochondria, forms a limited number of oligomeric clusters at ER-mitochondria contact sites in a cell. Although the number of the ERMES clusters appears to be regulated to maintain proper inter-organelle phospholipid trafficking, its underlying mechanism and physiological relevance remain poorly understood. Here, we show that mitochondrial dynamics control the number of ERMES clusters. Moreover, we find that ER stress causes dissociation of the ERMES clusters independently of Ire1 and Hac1, canonical ER-stress response pathway components, leading to a delay in the phospholipid transport from the ER to mitochondria. Our biochemical and genetic analyses strongly suggest that the impaired phospholipid transport contributes to phospholipid accumulation in the ER, expanding the ER for ER stress attenuation. We thus propose that the ERMES dissociation constitutes an overlooked pathway of the ER stress response that operates in addition to the canonical Ire1/Hac1-dependent pathway.


Distinct features of distant metastasis and lymph node stage in lung adenocarcinoma patients with epidermal growth factor receptor gene mutations.
The influence of epidermal growth factor receptor (EGFR) mutation status on distant and lymph node metastasis is not fully understood. Ninety-five consecutive patients with stage IV lung adenocarcinoma, who had been examined for the EGFR mutation status, were retrospectively analyzed with regard to numbers of distant metastasis and clinical stage of lymph node metastasis at the time of diagnosis. While EGFR mutation status did not influence the presence or absence of distant metastasis in the lung, brain, or liver, patients with EGFR mutations demonstrated a significantly greater number of metastatic lesions in the lung (median: 85 vs. 4, P=0.01) and the brain (11 vs. 3.5, P=0.04). On the other hand, patients with EGFR mutations showed a significantly lower lymph node staging (P<0.01). The presence of EGFR mutations in patients with lung adenocarcinoma correlates with lower lymph node stage and a greater number of metastatic lesions in the lung and brain.


Public opinion analysis regarding the uses of master settlement agreement (MSA) funds.
In the present research, we assessed the relationship between characteristics of the residents of Long Beach, California, a typical city in America, and their opinions regarding the uses of master settlement agreement (MSA) funds. The statistical analyses used in the present research included univariate frequency distributions, cross-tabulations, and classification and regression trees. The results indicate that the majority of Long Beach residents share the opinion that the MSA funds should be allocated to health programmes. They do not, however, feel that these funds need to be earmarked solely for smoking prevention or cessation. Due to state budget deficits, legislators may strongly advocate for the MSA funds to be used for non-health purposes. Our findings provide support for community advocates who wish to bring the current uses of MSA funds and tobacco taxes to the forefront of national and international public debate.


Retracted: Nonalcoholic Fatty Liver Hepatocyte-Derived lncRNA MALAT1 Aggravates Pancreatic Cell Inflammation via the Inhibition of Autophagy by Upregulating YAP.
[This retracts the article DOI: 10.1155/2022/2930960.].


Effect of renal function on serum concentration of 1,5-anhydroglucitol in type 2 diabetic patients in chronic kidney disease stages I-III: A comparative study with HbA1c and glycated albumin.
1,5-Anhydroglucitol (1,5-AG) is a new blood glucose control marker reflecting temporary glucose elevations. However, 1,5-AG is of limited value in patients with advanced renal insufficiency. The aim of the present study was to assess the correlation between 1,5-AG levels and renal function in patients with earlier stages of nephropathy compared with another two markers of diabetes control, namely HbA1c and glycated albumin (GA). The following parameters were measured in 377 patients with type 2 diabetes: HbA1c, serum concentrations of 1,5-AG, GA and creatinine, hemoglobin, urinary albumin/creatinine ratio, and urinary excretion of α1 -microglobulin (A1M). Estimated glomerular filtration rate (eGFR) was calculated according to the Cockgroft-Gault formula. There was a negative correlation between 1,5-AG and renal function (r = -0.18; P < 0.001). Concentrations of 1,5-AG were, on average, 27.2% lower in patients with glomerular hyperfiltration (eGFR >120 mL/min) compared with patients with moderate renal impairment (eGFR 30-59 mL/min; P = 0.016). In contrast, HbA1c, GA levels and urinary A1M excretion did not differ between the two patient groups. The mean age of patients with eGFR 30-59 mL/min was substantially higher than that of patients with glomerular hyperfiltration (P < 0.001). Thus, an age-related change in the renal glucose threshold could be the reason for the observed correlation between 1,5-AG and renal function. In clinical practice, age and renal function must be taken into consideration when interpreting 1,5-AG levels, even in the absence of advanced renal impairment.


Combinational chemotherapy of L1210 and L1210/ARA-C leukemia with 5-AZA-2'-deoxycytidine and beta-2'-deoxythioguanosine.
The in vitro and in vivo antineoplastic activity of 5-AZA-2'-deoxycytidine (5-AZA-CdR) and beta-2'-deoxythioguanosine (TGdR) on L1210 and L1210/ARA-C (resistant to cytosine arabinoside) leukemic cells was investigated. 5-AZA-CdR was a very potent cytotoxic agent against the L1210 leukemia cells. This analogue was inactive against L1210/ARA-C leukemic cells because these cells lack deoxycytidine kinase, the enzyme that converts 5-AZA-CdR to its active nucleotide form. TGdR was a potent cytotoxic agent to both L1210 and L1210/ARA-C leukemic cells. In mice which were injected simultaneously with both L1210 and L1210/ARA-C leukemic cells, the drug combination of 5-AZA-CdR plus TGdR had a very potent antineoplastic activity and produced long-term survivors. Either agent alone did not produce any long-term survivors in the mice with L1210 and L1210/ARA-C leukemia. This experimental model indicates that 5-AZA-CdR plus TGdR is an interesting drug combination for the treatment of leukemia with drug-resistant cells.


Experimental demonstration of Fourier synthesis of an annular ultrasonic intensity distribution.
Ultrasonic source velocity distributions can be manipulated to provide beam shaping, as demonstrated by much previous work on focussing, side-lobe reduction and the production of Gaussian beam profiles. In principle, other beam profiles can be specified to order using inverse source calculations. We have presented a Fourier optics calculation for the source velocity distribution required to produce a desired distribution in intensity at a given axial distance. In this Paper, we present experimental verification of this approach using a 3.8 cm radius lead metaniobate transducer divided into 10 annuli of equal width, operated at 850 kHz continuous wave. The radiofrequency (RF) voltages supplied to each annulus were adjusted to approximate a source distribution calculated to produce an annular intensity distribution with inner and outer radii of 1.5 and 2.5 cm, respectively, at an axial distance of 30 cm in water. Good experimental verification of predicted intensities was achieved.


Dietary ethylenediamine dihydroiodide improves intestinal health in Cherry Valley ducks.
This study investigated the effect of ethylenediamine dihydroiodide (EDDI) on the growth performance, thyroid function, immune function, intestinal development, intestinal permeability, intestinal barrier functions and microbial characteristics of Cherry Valley ducks. The results showed that the addition of EDDI significantly increased body weight, average daily gain, serum level of lymphocytes, basophils, triiodothyronine, thyroxine and thyrotropin, villus height, and villus height-to-crypt depth ratio, and significantly decreased crypt depth, diamine oxidase, serum D-Lactic acid of ducks (P < 0.05). EDDI also significantly up-regulated the mRNA expression of zonula occludens-1, zonula occludens-2, zonula occludens-3, mucin 2, secretory immunoglobulin A, interleukin-10 and avian β-defensin 2 in the jejunum and ileum (P < 0.05), and down-regulated the mRNA expression of occludin and interleukin-6 in the jejunum and ileum. Additionally, the addition of EDDI significantly increased cecal level of acetic acid, propionic acid, butyric acid (P < 0.05). Cecal microbiome analysis indicated that the addition of EDDI significantly increased the relative abundance of these microorganisms that can produce short-chain fatty acids, mainly including Actinobacteria, Verrucomicrobia, Clostridiales and Lactobacillales, and decreased the relative abundance of pathogenic bacteria Deferribactere. Interestingly, triiodothyronine and thyroxine levels were highly positively correlated with the relative abundance of Actinobacteria. These results revealed that the addition of EDDI could promote the growth and development of meat ducks by improving their thyroid function, immune function, intestinal development and intestinal barrier functions of ducks.


Modified motor unit number index (MUNIX) algorithm for assessing excitability of alpha motor neuron in spasticity.
The understanding of the spasticity mechanism is still a problem in the literature, as its definition can be made on the basis of more than one parameter. Therefore, we studied alpha motor neuron excitability, dynamic changes based on force production, and patellar tendon (T) reflex in spasticity and healthy control groups. Alpha motor neuron excitability, force production, and patellar T reflex were evaluated through three different test protocols. Motor Unit Number Index (MUNIX) measurement was applied for understanding motor neuron pool properties in the first protocol. Voluntary force production and patellar T reflex parameters were evaluated by voluntary force production and triggering patellar T reflex. Twenty spasticity and 20 healthy volunteers participated in the study. In the spasticity group, both MUNIX numbers and Motor Unit Size Index (MUSIX) numbers were lower than those in the control group. The results for the Ideal Case Motor Unit Count (ICMUC) parameter show that there is no significant difference between spasticity and healthy individuals for low-level contractions, whereas there is a significant difference for high-level contractions (p < 0.05). In the spasticity group, an increase was observed in the ratio of maximal voluntary force to the T reflex triggered force production (Tf/Vf). Spasticity and healthy subjects can be distinguished easily and clearly by evaluating the changes in both kinesiological and electrophysiological findings and the decreasing threshold in the alpha motor neuron pool. This study shows that such combined methods, which allow the evaluation of the alpha motor neuron pool, as well as kinesiological and electrophysiological parameters, are tools that cannot be overlooked in understanding spasticity.


Use of a laryngeal tube for sialolithotomy in a pediatric patient with left vocal cord paralysis: a case report.
The laryngeal tube (LT), a closed esophageal supraglottic device comprising pharyngeal and esophageal cuffs, is used for emergency airway management. However, it is not often used in intraoperative airway management. A 9-year-old boy was scheduled for a sialolithotomy for sialolithiasis. He had a history of surgery for tetralogy of Fallot and had undergone vocal cord fusion for postoperative left-sided vocal cord paralysis. Following a strong request by the mother to avoid tracheal intubation to reduce the risk of bilateral vocal cord paralysis, management without intubation was initially considered in the preoperative anesthesia plan. Airway management was planned using an LT in case of ventilation failure due to positional abnormalities. Although some leakage was observed during intraoral surgery, it was quickly resolved by adjusting the position of the LT outside the sterile surgical field. The LT may be a viable option in cases where tracheal intubation is not preferred.


Graphical approach to model reduction for nonlinear biochemical networks.
Model reduction is a central challenge to the development and analysis of multiscale physiology models. Advances in model reduction are needed not only for computational feasibility but also for obtaining conceptual insights from complex systems. Here, we introduce an intuitive graphical approach to model reduction based on phase plane analysis. Timescale separation is identified by the degree of hysteresis observed in phase-loops, which guides a "concentration-clamp" procedure for estimating explicit algebraic relationships between species equilibrating on fast timescales. The primary advantages of this approach over Jacobian-based timescale decomposition are that: 1) it incorporates nonlinear system dynamics, and 2) it can be easily visualized, even directly from experimental data. We tested this graphical model reduction approach using a 25-variable model of cardiac β(1)-adrenergic signaling, obtaining 6- and 4-variable reduced models that retain good predictive capabilities even in response to new perturbations. These 6 signaling species appear to be optimal "kinetic biomarkers" of the overall β(1)-adrenergic pathway. The 6-variable reduced model is well suited for integration into multiscale models of heart function, and more generally, this graphical model reduction approach is readily applicable to a variety of other complex biological systems.


Effects of insoluble and soluble fibers isolated from barley on blood glucose, serum lipids, liver function and caecal short-chain fatty acids in type 2 diabetic and normal rats.
Large prospective cohort studies suggested an important role of cereal insoluble fiber in the prevention and management of type 2 diabetes, which challenge the traditional view that viscosity and solubility are the main driving factors for these beneficial effects of dietary fiber. To evaluate the anti-diabetic effects of insoluble- (BIF) and soluble fibers (BSF) enzymatically isolated from barley, a conventional rat model and a type 2 diabetes rat model were used. Our results showed that 4-week treatment of BIF or BSF effectively reduced FBG in the diabetic condition, with caecal level of propionic acid and minor SCFAs increased by BIF and that of butyric acid and insulin sensitivity improved by BSF, respectively. The two treatments further ameliorated liver function, judged by the recovered serum level of ALT, albumin and total protein levels. BIF and BSF also increased HDL-C and decreased serum MDA. In normal rats, BIF and BSF showed a hypolipidaemic effect in triglycerides and LDL-C, reduced body weight and enhanced the caecal production of minor SCFAs. Furthermore, the two treatments reduced the caecal level of butyric acid while BSF increased that of propionic acid. In conclusion, BIF could exert anti-diabetic effects that might via a different mechanism from BSF.


Genetic regulation of the immune response to hepatitis B surface antigen (HBsAg). II. Qualitative characteristics of the humoral immune response to the a, d, and y determinants of HBsAg.
It was previously demonstrated that the murine humoral immune responses to the common a and subtype-specific d determinants of HBsAg are H-2 restricted. The H-2q haplotype confers high responsiveness and the H-2s haplotype low responsiveness to nonresponsiveness to both determinants. We have now demonstrated that the H-2s haplotype also confers nonresponsiveness to the subtype-specific y determinant as well. Studies of H-2 congenic (nonresponder X responder)F1 and backcross mice indicated that responsiveness was inherited as a dominant trait, with no gene dosage effects observed. Qualitative characteristics of the humoral anti-a and anti-d responses were evaluated with respect to strain variation, kinetics, antigen specificity and antibody titer, affinity, and subclass distribution. Unique immune response patterns were observed for each H-2 haplotype studied. On the basis of these patterns, it was possible to construct a hierarchy of responsiveness to HBsAg of the ad subtype as follows: high responders, H-2q and H-2d; intermediate responders, H-2a greater than H-2b greater than H-2k; and nonresponders, H-2s.


A 5-year prospective radiographic evaluation of marginal bone levels adjacent to parallel-screw cylinder machined-neck implants and rough-surfaced microthreaded implants using digitized panoramic radiographs.
The purpose of this split-mouth study was to compare macro- and microstructure implant surfaces at the marginal bone level over five years of functional loading. From January to February 2006, 133 implants (70 rough-surfaced microthreaded implants and 63 machined-neck implants) were inserted in the mandible of 34 patients with Kennedy Class I residual dentitions and followed until December 2011. Marginal bone level was radiographically determined at six time points: implant placement (baseline), after the healing period, after six months, and at two years, three years, and five years follow-up. Median follow-up time was 5.2 years (range: 5.1-5.4). The machined-neck group had a mean crestal bone loss of 0.5 mm (0.0-2.3) after the healing period, 1.1 mm (0.0-3.0) at two years follow-up, and 1.4 mm (0.0-2.9) at five years follow-up. The rough-surfaced microthreaded implant group had a mean bone loss of 0.1 mm (-0.4 to 2.0) after the healing period, 0.5 mm (0.0-2.1) at two years follow-up, and 0.7 mm (0.0-2.3) at five years follow-up. The two implant types showed significant differences in marginal bone levels. Rough-surfaced microthreaded design caused significantly less loss of crestal bone levels under long-term functional loading in the mandible when compared to machined-neck implants.


Anger, dissociation, and PTSD among male veterans entering into PTSD treatment.
Prior research suggests that dissociation and anger are risk factors for the development of posttraumatic stress disorder (PTSD). Research found that trauma survivors with higher levels of anger also report more severe PTSD overall. Studies also support a relationship between PTSD severity and dissociation. Only one prior study of sexual assault survivors by Feeny, Zoellner, and Foa (2000) examined the relationships among dissociation, anger, and PTSD. While Veterans have been found to report high levels of anger and dissociation, the relationship between these factors and PTSD has not been examined among Veterans. This paper examines the relationship among anger, dissociation, and PTSD in treatment-seeking Veterans who presented for evaluation at the PTSD Clinic in the VA Ann Arbor Healthcare System during a four year period. Anger and dissociation predicted PTSD, hyperarousal, and avoidance/numbing severity while dissociation predicted intrusive severity. The implications of these results for clinical practice are discussed.


Correlation between inositol phospholipid hydrolysis and substance P receptors in rat CNS.
The undecapeptide substance P is a neurotransmitter candidate in the mammalian central and peripheral nervous system. Although the distribution of substance P-like immunoreactivity within the central nervous system (CNS) is well established, the recent identification and autoradiographic localization of specific substance P-binding sites has revealed numerous areas of mismatch between peptide levels and numbers of such sites. Previous studies have shown that substance P stimulates the hydrolysis of inositol phospholipids in peripheral tissues and in the hypothalamus, probably through stimulation of a polyphosphoinositide-specific phospholipase C (refs 9-11). Inositol phospholipid hydrolysis has been implicated in the mobilization of cytosolic calcium following receptor activation in several neurotransmitter and hormonal systems. We have therefore investigated the distribution of 3H-labelled substance P binding sites within various rat brain regions and correlated this with the rate of substance P-induced hydrolysis of inositol phospholipids in the same areas of the CNS. We found that the rate of inositol phospholipid hydrolysis was proportional to the number of binding sites specific for 3H-substance P, suggesting that binding sites revealed by 3H-substance P autoradiography correspond to functional substance P receptors.


[Assessment of practices in postoperative analgesia in caesarean before and after implementation of an information program].
To assess the improvement of practices in postoperative analgesia after a cesarean section post implementation of a corrective program. Prospective impact study. After obtaining ethics approval, we included all patients undergoing a cesarean section at Montpellier University Hospital during February 2011 (PRE group) and March 2012 (POST group). The patients were interviewed on the fourth day postpartum about pain management and related data was collected from the chart. From March 2011 to February 2012, training sessions were held for the paramedical and medical teams. Sixty patients were included in each group. The two groups were not significantly different. The mean overall numeric rating scale worst pain score between Day 0 and Day 4 in POST group was lower (5.5±2.5 vs. 6.5±2.4 p<0.01) and impairment during mobilization decreased significantly. Compliance with protocols improved in the POST group: the number of women receiving full analgesia regiment increased from 12% to 68% between PRE and POST period. After an awareness campaign of the paramedical and medical staff, we succeeded in improving significantly the routine use of analgesics regardless of their level. Nevertheless healthcare professionals still seem reluctant to administer opioids.


The impact of greed on academic medicine and patient care.
To what extent is the increasing emphasis on profit generation at US academic institutions shackling intellectual freedom and compromising healthcare?


The nervous system-specific S-100 antigen in cerebrospinal fluid of multiple sclerosis patients.
The nervous system-specific S-100 antigen has been found in cerebrospinal fluid (CSF) of 13 out of 18 patients with multiple sclerosis (MS), whereas it was undetectable in either of the 11 control patients with minor psychic disturbances or with neurological disorders not usually associated with apparent parenchymal lesion. The levels of the antigen appeared to be higher in CSF of patients in the acute phase of the disease. Though the small number of cases hampers final statements, the S-100 in CSF might serve as a possible index of active cell injury in the central nervous system underlying the pathogenesis of MS.


Recent Advances in the Role of Diet in Bone and Mineral Disorders in Chronic Kidney Disease.
Chronic kidney disease mineral and bone disease (CKD-MBD) is a common complication of kidney disease and is strongly influenced by diet. The purpose of this manuscript is to review recent advances in the role of diet in CKD-MBD over the last 5 years. Many of the recent studies examining the role of diet in CKD-MBD have focused on the adverse effects of high phosphorus consumption on bone health and metabolism. In general, the studies have shown that high phosphorus consumption worsens markers of bone and mineral metabolism but that eating a diet with a calcium to phosphorus ratio closer to 1:1 can attenuate some of these effects. Recent studies also showed that dietary counseling is efficacious for improving markers of CKD-MBD. High consumption of phosphorus aggravates CKD-MBD. Dietary counseling may ameliorate these effects, for example, by consuming diets with higher calcium to phosphorus ratios.


Plasma noradrenaline response to sustained handgrip in patients with essential hypertension.
The responses of plasma noradrenaline, arterial blood pressure, and heart rate to sustained handgrip at 30% maximal voluntary contraction were studied in untreated patients with essential hypertension and in healthy subjects of comparable age. There were no significant differences between these two groups in the intensity and duration of handgrip. Increases in heart rate and blood pressure induced by the effort were similar in hypertensive patients and normotensive control subjects, whereas the absolute levels of blood pressure were considerably higher in the patients. In the first 1-2 min of exercise the increases in plasma noradrenaline concentration were similar in both groups. Subsequently, plasma noradrenaline concentration tended to plateau in hypertensive patients while in control subjects it continued to increase. The elevation of plasma noradrenaline in the last minute of effort was, therefore, significantly smaller in hypertensive patients than in the control group.


Characterization of the differentiated antioxidant profile of human saliva.
Saliva is armed with various defense mechanisms, such as the immunological and enzymatic defense systems. In addition, saliva has the ability to protect the mucosa against mechanical insults and to promote its healing via the activity of epidermal growth factor. However, another defense mechanism, the antioxidant system, exists in saliva and seems to be of paramount importance. The most interesting finding of the present study was the demonstration of the existence of much higher concentrations of the various salivary molecular and enzymatic antioxidant parameters in the parotid saliva compared with the submandibular/sublingual saliva. For example, peroxidase, superoxide dismutase, uric acid, and total antioxidant status were higher in resting parotid saliva compared with resting submandibular/sublingual saliva by 2405, 235, 245, and 147%, respectively. Another important finding was the distinction between the salivary antioxidant system and the immunological and enzymatic protective systems, as represented by the salivary concentrations of secretory IgA and lysozyme, respectively. These findings suggest that the profound antioxidant capacity of saliva secreted from parotid glands is related either to the different physiological demands related to eating (parotid predominance), to oral integrity maintenance (submandibular/sublingual predominance), or to the high content of deleterious redox-active transitional metal ions present in parotid saliva. This also may signify that our oral cavity environment is only partially protected against oxidative stress during most of the day and night.


Influence of polar side chains modifications on the dual enkephalinase inhibitory activity and conformation of human opiorphin, a pain perception related peptide.
The dual inhibitory action of the pain related peptide opiorphin (H-Gln-Arg-Phe-Ser-Arg-OH) against neutral endopeptidase (NEP) and aminopeptidase N (AP-N) was further investigated by a SAR study involving minor modifications on the polar side chains of Arg residues and glycosylation with monosaccharides at Ser. None of them exerted dual or individual inhibitory potency superior than opiorphin. However, the correlations deduced offer further proof for the key role of these residues upon the binding and bioactive conformational stabilization of opiorphin. NMR conformational studies on the glycopeptides suggest that they are still very flexible compounds that may attain their respective bioactive conformations.


Effects of prostaglandin synthesis inhibitors on tumor growth and vascularization. Experimental studies in the rat.
The growth rate (studied by mean tumor dry weight) and vascularization (studied by microangiography) of two transplantable rat tumors, a 20-methylcholanthrene-induced fibrosarcoma and a hepatoma, were significantly reduced by three prostaglandin synthesis inhibitors, indomethacin, diclofenac-sodium and aspirin, irrespective of whether the drugs were administered early or late during tumor growth.


Can aged biochar offset soil greenhouse gas emissions from crop residue amendments in saline and non-saline soils under laboratory conditions?
Applying biochar in association with crop residues might optimize costs and effectiveness in the reclamation of saline soils. Here, we explored the potential effects of biochar in association with crop residue amendments on soil greenhouse gas (GHG) emissions, and microbial communities. Previously, we found that soil N2O emission significantly increased with increasing salinity levels followed by cotton straw addition. In the present study, microcosm experiments were performed to investigate the interaction of salinity (0 and 1.2% salt) with the aging of biochar following soil amendments over an incubation period of 80 days. The results indicated that N2O emissions were approximately 5-10 times higher in saline soils than in non-saline soils, and the cumulative N2O emissions following two straw amendments treatment were the highest of all the treatments. Salinity increased the contribution of nitrification to soil N2O emissions stimulated by the cotton straw amendments, and aged biochar performed better in decreasing soil N2O emissions in saline soils than in non-saline soils. In addition, aged biochar increased soil C mineralization and CO2 emissions under saline conditions. Soil CO2 and N2O emissions were affected by both soil abiotic and biotic factors under non-saline and saline conditions. Moreover, much more specific but fewer microbial groups survived and utilized crop residues under saline than non-saline conditions, and aged biochar decreased salt stress in soil microorganisms. These findings indicated that aged biochar and crop residues together would be an optimal way to address soil C storage and mitigate N2O emissions under saline conditions.


Correction to: Bilobalide Induces Neuronal Differentiation of P19 Embryonic Carcinoma Cells via Activating Wnt/β-Catenin Pathway.
The original version of this article unfortunately contained an error in Figures 1A and 4C.


2020 webPOISONCONTROL data summary.
Increasing use of the internet for health information has decreased utilization of traditional telephone-based poison centers in the United States. webPOISONCONTROL®, a browser-based tool and app was launched to meet the growing demand for online, personalized recommendations for human poison exposures. This study was conducted to characterize webPOISONCONTROL cases and highlight its potential for real-time monitoring of poisoning. Case data for all completed, nonduplicated public cases entered in 2020 were analyzed using a custom Qlik Sense dashboard. Of the 156,202 cases, 52.9% occurred in children younger than 4 years. Most cases (109,057, 69.8%) were initially triaged to home, 28.4% were advised to call Poison Control, and 1.7% were referred to the ED. Follow-up was available for 33.3% of home-triaged cases; 1.7% of those had a change in triage recommendation. Pharmaceuticals were implicated in 41.5% of cases (nonpharmaceuticals in 58.5%). Ingestion was the most common route (88.4%, 138,012). One-time double dose therapeutic error cases were implicated in 17,901 cases (27.6% of pharmaceutical cases). Cosmetics (13.9%) and cleaning substances (12.9%) were the most frequent substance categories. Melatonin was the most frequently implicated generic substance (4.5% of cases). Most (72.0%) cases had no effect (21.4%), a minor effect (3.9%) or were minimally toxic with unknown outcome (46.7%). There were no deaths, 17 major outcomes (0.01%), and 26.7% of cases had potentially toxic exposures with no outcome determination. In 2020, webPOISONCONTROL handled 7.3% as many human poison exposure cases as were reported to U.S. phone-based poison centers. Online cases are skewed towards younger ages (53% in children younger than 4 years vs 37% of phone-based cases) and towards nonpharmaceuticals (58.5% vs 43.5%). Near real-time data visualizations enabled detection of COVID-19-related increases in exposures to hand sanitizers and cleaners, illustrating the public health surveillance and hazard detection capabilities of webPOISONCONTROL. The webPOISONCONTROL tool provides a safe, quick and fully-automated alternative to those who are unable or unwilling to use the telephone to call a traditional poison center.