Alternative shock index cutoffs for pediatric patients outperform the Shock Index Pediatric Age-adjusted (SIPA) on strength of association with adverse outcomes in pediatric trauma patients.
The shock index is a tool for evaluating critically ill patients that is defined as the ratio of their heart rate divided by systolic blood pressure. The SI is associated with outcomes in adult trauma patients. The Shock Index Pediatric Age-adjusted was developed as a pediatric-specific tool to account for the physiologic differences of children of varying ages. There is growing interest in Shock Index Pediatric Age-adjusted, which is associated with adverse outcomes in pediatric trauma. We hypothesized that alternative shock index cutoffs based on the Advanced Trauma Life Support or the Pediatric Advanced Life Support vital sign reference ranges would outperform Shock Index Pediatric Age-adjusted. We analyzed a retrospective cohort of pediatric trauma patients (age 1 to 16 years old) in the American College of Surgeons Trauma Quality Programs Participant Use File from 2010 to 2018. The primary outcome measure was in-hospital mortality. The Shock Index Pediatric Age-adjusted was compared to an Advanced Trauma Life Support-based and a Pediatric Advanced Life Support-based shock index cutoff system. Our findings were subsequently confirmed with a separate, internal validation data set. A total of 598,830 Trauma Quality Programs Participant Use File patients were included, 0.9% (n = 5,471) of whom died. For mortality, the Advanced Trauma Life Support-based system yielded the highest positive predictive value (15.8%; 95% confidence interval 15.0%-16.7%) compared with the Pediatric Advanced Life Support-based system (4.3%; 95% confidence interval 4.1%-4.5%). Both the Advanced Trauma Life Support-based and Pediatric Advanced Life Support-based systems achieved higher positive predictive values compared to Shock Index Pediatric Age-adjusted (2.6%; 95% confidence interval 2.5%-2.7%). The negative predictive values were not clinically different. Our findings were validated using a separate internal trauma database, in which the positive predictive value for mortality of the Advanced Trauma Life Support-based system was significantly higher than Shock Index Pediatric Age-adjusted (18.2% [95% confidence interval: 8.2%-32.7%] vs 2.9% [95% confidence interval: 1.6%-5.0%], P < .05). Advanced Trauma Life Support and Pediatric Advanced Life Support-based shock index cutoffs achieved higher positive predictive values and similar negative predictive values compared to Shock Index Pediatric Age-adjusted for adverse outcomes in pediatric trauma.


Magnetoencephalographic signatures of conscious processing before birth.
The concept of fetal consciousness is a widely discussed topic. In this study, we applied a hierarchical rule learning paradigm to investigate the possibility of fetal conscious processing during the last trimester of pregnancy. We used fetal magnetoencephalography, to assess fetal brain activity in 56 healthy fetuses between gestational week 25 and 40, during an auditory oddball paradigm containing first- and second-order regularities. The comparison of fetal brain responses towards standard and deviant tones revealed that the investigated fetuses show signs of hierarchical rule learning, and thus the formation of a memory trace for the second-order regularity. This ability develops over the course of the last trimester of gestation, in accordance with processes in physiological brain development and was only reliably present in fetuses older than week 35 of gestation. Analysis of fetal autonomic nervous system activity replicates findings in newborns, showing importance of activity state for cognitive processes. On the whole, our results support the assumption that fetuses in the last weeks of gestation are capable of consciously processing stimuli that reach them from outside the womb.


Cordon-bleu is an actin nucleation factor and controls neuronal morphology.
Despite the wealth of different actin structures formed, only two actin nucleation factors are well established in vertebrates: the Arp2/3 complex and formins. Here, we describe a further nucleator, cordon-bleu (Cobl). Cobl is a brain-enriched protein using three Wiskott-Aldrich syndrome protein homology 2 (WH2) domains for actin binding. Cobl promotes nonbundled, unbranched filaments. Filament formation relies on barbed-end growth and requires all three Cobl WH2 domains and the extended linker L2. We suggest that the nucleation power of Cobl is based on the assembly of three actin monomers in cross-filament orientation. Cobl localizes to sites of high actin dynamics and modulates cell morphology. In neurons, induction of both neurites and neurite branching is dramatically increased by Cobl expression-effects that critically depend on Cobl's actin nucleation ability. Correspondingly, Cobl depletion results in decreased dendritic arborization. Thus, Cobl is an actin nucleator controlling neuronal morphology and development.


Microbiota-derived tryptophan catabolites mediate the chemopreventive effects of statins on colorectal cancer.
Epidemiological studies have indicated an association between statin use and reduced incidence of colorectal cancer (CRC), and work in preclinical models has demonstrated a potential chemopreventive effect. Statins are also associated with reduced dysbiosis in the gut microbiome, yet the role of the gut microbiome in the protective effect of statins in CRC is unclear. Here we validated the chemopreventive role of statins by retrospectively analysing a cohort of patients who underwent colonoscopies. This was confirmed in preclinical models and patient cohorts, and we found that reduced tumour burden was partly due to statin modulation of the gut microbiota. Specifically, the gut commensal Lactobacillus reuteri was increased as a result of increased microbial tryptophan availability in the gut after atorvastatin treatment. Our in vivo studies further revealed that L. reuteri administration suppressed colorectal tumorigenesis via the tryptophan catabolite, indole-3-lactic acid (ILA). ILA exerted anti-tumorigenic effects by downregulating the IL-17 signalling pathway. This microbial metabolite inhibited T helper 17 cell differentiation by targeting the nuclear receptor, RAR-related orphan receptor γt (RORγt). Together, our study provides insights into an anti-cancer mechanism driven by statin use and suggests that interventions with L. reuteri or ILA could complement chemoprevention strategies for CRC.


Stabilizing Fe-N-C Catalysts as Model for Oxygen Reduction Reaction.
The highly efficient energy conversion of the polymer-electrolyte-membrane fuel cell (PEMFC) is extremely limited by the sluggish oxygen reduction reaction (ORR) kinetics and poor electrochemical stability of catalysts. Hitherto, to replace costly Pt-based catalysts, non-noble-metal ORR catalysts are developed, among which transition metal-heteroatoms-carbon (TM-H-C) materials present great potential for industrial applications due to their outstanding catalytic activity and low expense. However, their poor stability during testing in a two-electrode system and their high complexity have become a big barrier for commercial applications. Thus, herein, to simplify the research, the typical Fe-N-C material with the relatively simple constitution and structure, is selected as a model catalyst for TM-H-C to explore and improve the stability of such a kind of catalysts. Then, different types of active sites (centers) and coordination in Fe-N-C are systematically summarized and discussed, and the possible attenuation mechanism and strategies are analyzed. Finally, some challenges faced by such catalysts and their prospects are proposed to shed some light on the future development trend of TM-H-C materials for advanced ORR catalysis.


Palladium-Catalyzed Divergent Imidoylative Cyclization of Multifunctionalized Isocyanides: Tunable Access to Oxazol-5(4H)-ones and Cyclic Ketoimines.
A palladium-catalyzed tunable imidoylative cyclization of multifunctionalized isocyanides to construct diverse imine-containing heterocycles has been developed. Oxazol-5(4H)-one derivatives were obtained exclusively when allyl-2-benzyl(or allyl)-2-isocyanoacetates were used in the reaction with aryl triflates as electrophiles, whereas cyclic ketoimines were generated in the presence of aryl iodides with the allyl ester group remaining unreacted. The reactions proceeded smoothly under mild conditions with a wide functional group tolerance.


Relationship between polymorphism of DC-SIGN (CD209) gene and the susceptibility to pulmonary tuberculosis in an eastern Chinese population.
Dendritic cell-specific intracellular adhesion molecule-3-grabbing nonintegrin (DC-SIGN) is an important receptor for Mycobacterium tuberculosis on human dendritic cells. Previous studies have shown that the variation, especially the -871A/G and -336A/G in DC-SIGN promoter influenced the susceptibility to tuberculosis. We therefore investigated whether polymorphisms in the DC-SIGN gene were associated with susceptibility to tuberculosis in an eastern Chinese population. A total of 237 culture-positive pulmonary tuberculosis case patients and 244 controls were genotyped for -871A/G and -336A/G by pyrosequencing. Our results suggested that the 2 promoter variants of DC-SIGN gene were not associated with susceptibility to tuberculosis in Chinese. Further analysis showed that the allele -336G was associated with a protective effect against fever in pulmonary tuberculosis patients, but not against cavity formation. In addition, we compared the allelic frequencies of -871A/G and -336A/G in African, Caucasian, and Asian groups. The results showed that the tw forms of allelic frequencies detected Chinese individuals in our study were similar to the reported frequencies in other Asian populations but differed significantly from those in the African and Caucasian groups studied.


Inequities in Thyroid Cancer Care: Populations Most at Risk for Delays in Diagnosis and Treatment.
Background: Delays in treatment for thyroid cancer (TC) have been associated with higher overall mortality rates. However, few studies have explored the impact of health disparities on delayed presentation and treatment for TC. This study aims to investigate what patient sociodemographic factors contribute to delays in presentation and treatment of TC. Methods: Using the National Cancer Database, we identified patients diagnosed with well-differentiated TC between 2004 and 2016 who underwent thyroidectomy. Multivariable regression analyses were conducted to examine the impact of race, insurance status, income, and distance from treatment facility on time to surgical treatment, stage, the presence of distant metastases, and tumor size. Results: We identified 89,105 patients diagnosed with well-differentiated TC who underwent thyroidectomy. Nonwhite patients who were uninsured or had Medicare or Medicaid insurance were more likely to experience delays in care, present with higher stages at diagnosis, and have distant metastases and larger tumors at presentation. Distance from treatment facility was associated with delays in surgical treatment and higher stage at presentation. Conclusion: Delays in TC presentation and surgical treatment vary by race, insurance status, and patient location. Health care policies should focus on targeting at-risk individuals to reduce health care disparities in this disease.


Highly stereoselective anti SN2' substitutions of (Z)-allylic pentafluorobenzoates with polyfunctionalized zinc-copper reagents.
[reaction: see text] Allylic substitution reactions of zinc-copper organometallics on (Z)-allylic pentafluorobenzoates proceed with very high regioselectivity and excellent anti selectivity. The high fidelity in transfer of stereochemical information allowed a short synthesis of (+)-ibuprofen (97% ee).


Differences in nuclear thyroid hormone receptors among species.
Hepatic nuclear thyroid hormone receptors from rat, dog, chicken, and rainbow trout were compared. Receptor affinities for 3,5,3'-triiodo-L-thyronine (T3) were similar in preparations from rat, dog, and chicken, using isolated nuclei and nuclear extracts. Rainbow trout nuclear receptor showed a lower affinity for T3. Almost half of the receptors were released into the medium with rat and chicken nuclei, and 79.7 +/- 1.1% of the receptors were released with rainbow trout nuclei, when isolated nuclei were incubated with T3 at 22 degrees for 2 hr. The affinity constant of rat liver receptor for calf thymus DNA-cellulose at 0.17 M KCl, pH 7.4, was 3.98 +/- 1.47 x 10(5) M-1, when determined using DNA-cellulose columns. The number of salt bridges involved in DNA binding of the rat receptor was 5.73 +/- 0.38. When receptor-DNA interactions were compared among species, significant differences were found, but the receptors from dog and rainbow trout liver were similar. Sephacryl S-200 column chromatography showed that chicken receptor had a Stokes radius significantly smaller than that of rat receptor. Partial proteolysis of T3-receptor complex using trypsin alpha-chymotrypsin, elastase, and papain produced distinct T3-binding fragments in different species. Our data provide evidence that nuclear thyroid hormone receptors from different species have significant structural dissimilarities.


Simple methods to test the accuracy of MRgFUS robotic systems.
Robotic-assisted diagnostic and therapeutic modalities require a highly accurate performance to be certified for clinical application. In this paper, three simple methods for assessing the accuracy of motion of magnetic resonance-guided focused ultrasound (MRgFUS) robotic systems are presented. The accuracy of motion of a 4 degrees of freedom robotic system intended for preclinical use of MRgFUS was evaluated by calliper-based and magnetic resonance imaging (MRI) methods, as well as visually by performing multiple ablations on a plastic film. The benchtop results confirmed a highly accurate motion in all axes of operation. The spatial positioning errors estimated by MRI evaluation were defined by the size of the imaging pixels. Lesions arrangement in discrete and overlapping patterns confirmed satisfactory alignment of motion trajectories. We believe the methods presented here should serve as a standard for evaluating the accuracy of motion of MRgFUS robotic systems.


Electrochemical behaviour of 2,8-dihydroxyadenine at a glassy carbon electrode.
The electrochemical behaviour of 2,8-dihydroxyadenine (2,8-DHA)- the main adenine oxidation product- has been investigated over a wide pH range at a glassy carbon electrode (GCE) using cyclic, differential pulse and square wave voltammetry. The oxidation of 2,8-DHA is a quasi-reversible process, pH dependent and occurs with the formation of a main oxidation product, P(2,8-DHA), that strongly adsorbs on the electrode surface. The reduction of 2,8-DHA also occurs and is a reversible process in the absence of molecular oxygen. In electrolytes with pH between 4 and 9 two consecutive reversible charge transfer reactions were identified. However, it was observed that O(2) interfered with the reductive electron transfer process of 2,8-DHA and that, in the presence of oxygen, the reduction of 2,8-DHA occurs at less negative potentials than in the absence of oxygen.


Deletion loop mutagenesis of the nifL promoter from Klebsiella pneumoniae: role of the -26 to -12 region in promoter function.
Nine single C-to-T transitions were introduced into the -26 to -12 region of the Klebsiella pneumoniae nifL promoter by bisulphite mutagenesis of M13 heteroduplexes containing a 15 nucleotide single-stranded loop. Mutant promoter fragments were inserted into translational lac fusion vectors to utilise beta-galactosidase activity as a measure of promoter efficiency. Mutations in invariant nucleotides found in the consensus sequence for nif promoters gave a strong 'down' promoter phenotype with respect to transcriptional activation. Mutations in semi-conserved residues had a much weaker down phenotype, whereas a mutation which increased homology to the consensus sequence enhanced promoter strength. One mutant showed increased activation by ntrC and decreased activation by nifA.


An ion mobility-enabled and high-efficiency hybrid scan approach in combination with ultra-high performance liquid chromatography enabling the comprehensive characterization of the multicomponents from Carthamus tinctorius.
Liquid chromatography/mass spectrometry (LC/MS) is extensively applied for the untargeted/targeted analyses of the herbal components, utilizing data-dependent acquisition (DDA) or data-independent acquisition (DIA) to record the fragmentation information useful for the structural elucidation. A new trend recently has emerged by integrating DDA and DIA to render the hybrid scan, which, unfortunately, has rarely been reported. Herein, by using the Vion™ ion-mobility quadrupole time-of-flight mass spectrometer, a hybrid scan strategy (HDMSE-HDDDA) was presented and validated by the untargeted characterization of the multicomponents from Carthamus tinctorius (safflower), in combination with reversed-phase ultra-high performance liquid chromatography (RP-UHPLC). Good chromatographic separation was achieved on an HSS T3 column within 26 min, while HDMSE-MS/MS was used to acquire the collision-induced dissociation MS2 data in the negative mode. Automatic workflows (e.g., data correction, precursors/product ions matching, and peak annotation) were well established on UNIFI™ (incorporating an in-house library recording 261 known compounds) to process the obtained MS2 data. Compared with single DDA or DIA, the hybrid approach of HDMSE-HDDDA better balanced between the coverage and reliability, led to high-definition MS spectra, offered useful collision cross section (CCS) information, and showed satisfactory identification performance comparable to MSE. A total of 141 components (involving 41 quinochalcones, 66 flavanols/flavones, 11 flavanones, 6 organic acids, 1 polyacetylene, and 16 others) were characterized from safflower. Moreover, CCS prediction could assist isomers characterization, to some extent. Conclusively, this hybrid scan approach enables a dimension-enhanced MS data acquisition strategy providing the complementary structural information, which more suits the chemical characterization of complex samples.


Real-time Detection of Patient Head Position and Cephalometric Landmarks from Neuro-Interventional Procedure Images Using Machine Learning for Patient Eye-Lens Dose Prediction.
A deep learning (DL) model has been developed to estimate patient-lens dose in real-time for given exposure and geometric conditions during fluoroscopically-guided neuro-interventional procedures. Parameters input into the DL model for dose prediction include the patient head shift from isocenter and cephalometric landmark locations as a surrogate for head size. Machine learning (ML) models were investigated to automatically detect these parameters from the in-procedure fluoroscopic image. Fluoroscopic images of a Kyoto Kagaku anthropomorphic head phantom were taken at various known X (transverse) and Y (longitudinal) shifts, as well as different magnification modes, to create an image database. For each image, anatomical landmark coordinate locations were obtained manually using ImageJ and are used as ground-truth labels for training. This database was then used to train the two separate ML models. One ML model predicts the patient head shift in both the X and Y directions and the other model predicts the coordinates of the anatomical landmarks. From the coordinates, the distance between these anatomical landmarks is calculated, and input into the DL dose-prediction model. Model performance was evaluated using mean absolute error (MAE) and mean absolute percentage error (MAPE) for the head-shift and landmark-coordinate models, respectively. The goal is to implement these two separate models into the Dose Tracking System (DTS) developed by our group. This would allow the DTS to automatically detect the patient head size and position for eye-lens dose prediction and eliminate the need for manual input by the clinical staff.


Enhanced protection of PDMS-embedded palladium catalysts by co-embedding of sulphide-scavengers.
For Pd-containing hydrodechlorination catalysts, coating with poly(dimethyl siloxane) (PDMS) was proposed earlier as promising protection scheme against poisoning. The PDMS coating can effectively repel non-permeating poisons (such as SO32-) retaining the hydrodechlorination Pd activity. In the present study, the previously achieved protection efficiency was enhanced by incorporation of sulphide scavengers into the polymer. The embedded scavengers were able to bind permeating non-ionic poisons (such as H2S) during their passage through PDMS prior to Pd contact which ensured an extended catalyst lifetime. Three scavenger types forming non-permeable sulphur species from H2S - alkaline, oxidative or iron-based compounds - were either incorporated into single-layer coats around individual Pd/Al2O3 particles or into a second layer above Pd-containing PDMS films (Pd-PDMS). Hydrodechlorination and hydrogenation were chosen as model reactions, carried out in batch and continuous-flow reactors. Batch tests with all scavenger-containing catalysts showed extended Pd protection compared to scavenger-free catalysts. Solid alkaline compounds (Ca(OH)2, NaOH, CaO) and MnO2 showed the highest instantaneous scavenger efficiencies (retained Pd activity=30-60%), while iron-based catalysts, such as nano zero-valent iron (nZVI) or ferrocene (FeCp2), proved less efficient (1-10%). When stepwise poisoning was applied, the protection efficiency of iron-based and oxidizing compounds was higher in the long term than that of alkaline solids. Long-term experiments in mixed-flow reactors were performed with selected scavengers, revealing the following trend of protection efficiency: CaO2>Ca(OH)2>FeCp2. Under field-simulating conditions using a fixed-bed reactor, the combination of sulphide pre-oxidation in the water phase by H2O2 and local scavenger-enhanced Pd protection was successful. The oxidizing agent H2O2 does not disturb the Pd-catalysed reduction, while the PDMS-incorporated scavenger considerably extends the catalyst life in the presence of H2S. This work demonstrates that the scavenger-based protection strategy is an effective means to increase the resistance of PDMS-embedded Pd against permeating poisons.


Polygenic Risk Scores Differentiating Schizophrenia From Bipolar Disorder Are Associated With Premorbid Intelligence in Schizophrenia Patients and Healthy Subjects.
Impairments in intelligence are more severe in patients with schizophrenia (SCZ) than in patients with bipolar disorder (BD) despite clinical and genetic similarities between the disorders. Genetic loci differentiating SCZ from BD, that is, SCZ-specific risk, have been identified. Polygenetic [risk] scores (PGSs) for SCZ-specific risk are higher in SCZ patients than in healthy controls (HCs). However, the influence of genetic risk on impaired intelligence is poorly understood. Here, we investigated whether SCZ-specific risk could predict impairments in intelligence in SCZ patients and HCs. Large-scale genome-wide association study datasets related to SCZ vs BD, childhood intelligence (CHI), and adulthood intelligence (n = 12 441-282 014) were utilized to compute PGSs. PGSs derived from the genome-wide association studies were calculated for 130 patients with SCZ and 146 HCs. Premorbid and current intelligence and the decline were measured in SCZ patients and HCs. Correlations between PGSs and intelligence functions were investigated. High PGSs for SCZ-specific risk were correlated with low premorbid intelligence in SCZ patients and HCs (β = -0.17, P = 4.12 × 10-3). The correlation was still significant after adjusting for diagnostic status (β = -0.13, P = .024). There were no significant correlations between PGSs for SCZ-specific risk and current intelligence or intelligence decline (P > .05). PGSs for CHI were lower in SCZ patients than in HCs (R2 = 0.025, P = .025), while the PGSs for CHI were not significantly correlated with premorbid and current intelligence, the decline, or the PGSs for SCZ-specific risk (P > .05). These findings suggest that genetic factors differentiating SCZ from BD might affect the pathogenesis of SCZ and/or pathological differences between SCZ and BD via the impairment of premorbid intelligence, that is, crystallized intelligence, while genetic factors for CHI might affect the pathogenesis of SCZ but not via impairments in intelligence.


A mortality risk score for septuagenarians undergoing orthotopic heart transplantation.
With septuagenarians undergoing orthotopic heart transplantation (OHT) more frequently, we aimed to develop a risk score for 1-year mortality in this population. Septuagenarian OHT recipients were identified from the UNOS registry between 1987 and 2018. The primary outcome was 1-year post-OHT mortality. Patients were randomly divided into derivation and validation cohorts. Associated covariates were entered into a multivariable logistic regression model. A risk score was created using the magnitudes of the odds ratios from the derivation cohort, and its 1-year post-OHT mortality prediction capacity was tested in the validation cohort. A total of 1156 septuagenarians were included, and they were randomly divided into derivation (66.7%, n = 771) and validation (33.3%, n = 385) cohorts. An 11-point risk score incorporating 4 variables was created, which included mechanical ventilation, serum bilirubin, serum creatinine, and donor age. The predicted 1-year mortality ranged from 4.2% (0 points) to 48.1% (11-points) (p < .001). After cross-validation, the c-index was 0.67 with a Brier score of 0.10. Risk scores above 3 points portended a survival disadvantage at 1-year follow-up (p < .001). This 11-point risk score for septuagenarians is predictive of mortality within 1-year of OHT and has potential utilization in improving recipient evaluation and selection of elderly patients.


Establishment of an induced pluripotent stem cell line from a Noonan syndrome patient with the heterozygote mutation p.S257L (c.770C > T) in RAF1 gene.
Noonan Syndrome (NS) is an inherited autosome dominant disorder syndrome, which can be caused by the mutations of serine/threonine kinase rapidly accelerated fibrosarcoma 1 (RAF1) gene. Here, an induced pluripotent stem cell (iPSC) line named WMUi022-A derived from urine cells (UCs) of a 9-year-old male NS patient with the heterozygote RAF1 gene mutation p.S257L (c.770C > T) was established through the commercial Sendai virus reprogramming kit. The pluripotent markers like OCT4 and SOX2 can be expressed positively in WMUi022-A, which can be induced into three germ layers in vitro as well as maintain a normal karyotype (46, XY).


Endothelin-I-mediated vasoconstriction: specific blockade by verapamil.
The capacity of three vasodilators that act by distinct mechanisms to reverse endothelin-I-mediated vasoconstriction was studied in 11 healthy nonsmoking male subjects (mean age +/- SEM, 26 +/- 2 years; mean weight +/- SEM, 74 +/- 2 kg) by use of brachial artery infusion and forearm strain-gauge plethysmography. Isoproterenol (cyclic adenosine monophosphate-mediated vasodilation), sodium nitroprusside (cyclic guanosine monophosphate-mediated vasodilation), and verapamil (L-type calcium channel blocker) were compared for capacity to reverse endothelin-I-mediated increase in forearm vascular resistance (FVR). Endothelin-I infusion increased FVR 1.9-fold in the control state. Isoproterenol infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable isoproterenol infusion rates, endothelin-I increased FVR similar to the control state (for 5 ng/min isoproterenol, endothelin-I increased FVR 1.85-fold; for 12.5 ng/min isoproterenol, endothelin-I increased FVR 2.03-fold). Similarly, sodium nitroprusside infusion decreased FVR with or without concurrent endothelin-I infusion; however, at comparable sodium nitroprusside infusion rates the endothelin-I increase in FVR was similar to control (for 0.48 micrograms/min sodium nitroprusside, endothelin-I increased FVR 1.89-fold; for 0.96 micrograms/min sodium nitroprusside, endothelin-I increased FVR 2.36-fold). In contrast, verapamil infusion decreased FVR with or without endothelin-I infusion. At a verapamil infusion rate of 19.1 microns/min, endothelin-I increase in FVR was comparable to control (for 19.1 microns/min verapamil, endothelin-I increased FVR 1.36-fold, less than the 1.0-fold increase in the control state; p < 0.05). Isoproterenol and sodium nitroprusside decreased FVR during concurrent endothelin-I infusion but did not reverse the endothelin-I effect. In contrast, verapamil reversed endothelin-I--induced vasoconstriction to control FVR, suggesting a specific antagonism of endothelin-I--mediated increase in FVR.


Toward environmentally-benign utilization of nonmetallic fraction of waste printed circuit boards as modifier and precursor.
Electronic waste, including printed circuit boards, is growing at an alarming rate due to the accelerated technological progress and the shorter lifespan of the electronic equipment. In the past decades, due to the lack of proper economic and environmentally-benign recycling technologies, a major fraction of e-waste generated was either destined to landfills or incinerated with the sole intention of its disposal disregarding the toxic nature of this waste. Recently, with the increasing public awareness over their environment and health issues and with the enaction of more stringent regulations, environmentally-benign recycling has been driven to be an alternative option partially replacing the traditional eco-unfriendly disposal methods. One of the most favorable green technologies has been the mechanical separation of the metallic and nonmetallic fraction of the waste printed circuit boards. Although metallic fraction, as the most profitable component, is used to generate the revenue of the separation process, the nonmetallic fraction (NMF) has been left isolated. Herein, the recent developments in the application of NMF have been comprehensively reviewed and an eco-friendly emerging usage of NMF as a value-added material for sustainable remediation has been introduced.


p16 protein expression and correlation with clinical and pathological features in osteosarcoma of the jaws: Experience of 37 cases.
In literature, no markers have been reported as predictive and prognostic factors in osteosarcoma of the jaw. A retrospective analysis of p16 expression was performed in 37 patients with high-grade osteosarcoma of the jaw to investigate its potential prognostic and predictive value. p16 positivity was found in 56.7% of cases. The absence of p16 expression was associated with an adverse disease-free survival (P = .003). At the multivariate Cox regression, positive margins were the only independent factor. In the subgroup of 17 patients who underwent neoadjuvant chemotherapy, a significant association was noted between p16 expression and pathological response to chemotherapy (P = .015) and the negativity of p16 increased the risk of negative outcome (P = .01). Our data indicate that the wide surgical margin is the most important prognostic factor. The expression of p16 confers greater sensitivity to chemotherapy and its loss of expression is associated with a worse prognosis.


One year of clinical experience in postdilution hemofiltration with online reinfusion of regenerated ultrafiltrate.
Hemofiltrate reinfusion (HFR) is characterized by the use of regenerated ultrafiltrate as replacement fluid. We set up a new technique, postdilution HFR (PD-HFR), aiming at increasing purification efficiency, treatment tolerance and at reducing inflammatory states. We performed PD-HFR in 6 uremic patients during 1 year. Dialysis efficacy, dialyzer blood loss and the behavior of cytokines were evaluated. No pyrogenic reactions or other adverse events were recorded. Treatment tolerance was excellent. We observed high urea extraction rates and optimal Kt/V values, high beta2-microglobulin (beta2m) extraction rates and a decrease in dialyzer blood loss; also IL-6 and TNF-alpha decreased significantly. Inversion of the standard HFR configuration has allowed us to improve the removal of both urea and beta2m, and to decrease dialyzer blood loss, with an optimal tolerance. Moreover, the decrease in cytokine levels might attenuate the uremic microinflammatory state.


Midlatency auditory evoked potentials in children: effect of age and general anaesthesia.
Midlatency auditory evoked potentials (MLAEP) are a promising tool for monitoring suppression of sensory processing during anaesthesia and might help to avoid awareness. MLAEP in children are different to those in adults and the exact changes during general anaesthesia are unknown. In 49 children of age between 2 and 12 yr, MLAEP were recorded before anaesthesia, during tracheal intubation, at steady-state balanced anaesthesia, and after extubation. MLAEP were recordable in all children in the awake (premedicated) state with latencies but not amplitudes dependent on children's age. MLAEP latencies significantly increased during tracheal intubation and steady-state anaesthesia. Changes in amplitudes were inconsistent. All MLAEP variables returned to near baseline values after extubation. The results of this study imply that MLAEP can successfully be recorded during anaesthesia in children above the age of 2 yr. Further studies are necessary before MLAEP might be applicable for monitoring purposes in paediatric anaesthesia.


Oxyphilic granular cell adenoma (oncocytoma) of the esophagus.
An oncocytoma of the esophagus is presented. The patient's chief complaint was dysphagia, and barium swallow suggested cricopharyngeus muscle hypertrophy. Exploration revealed an intramural mass in the cervical esophagus. Enucleation resulted in relief of symptoms. Pathological and immunohistochemical analysis demonstrated an oncocytoma of thyroid origin.


Electrical synapses interconnecting axons revealed in the optic nerve head - a novel model of gap junctions' involvement in optic nerve function.
To characterize newly discovered electrical synapses, formed by connexin (Cx) 36 and 45, between neighbouring axons within the optic nerve head. Twenty-five Wistar rats were killed by CO2 inhalation. Proximal and distal optic nerve (ON) stumps were collected and processed for immunostainings, electron microscopy (EM) with immunogold labelling, PCR and Western blots (WB). Additional 15 animals were deeply anaesthetized, and flash visual evoked potentials (fVEP) after retrobulbar injection of saline (negative control) or 100 μm meclofenamic acid solution (gap junctions' blocker) were recorded. Human paraffin cross-sections of eyeballs for immunostainings were obtained from the Human Eye Biobank for Research. Immunostainings of both rat and human ON revealed the presence of Cx45 and 36 colocalizing with β3-tubulin, but not with glial fibrillary acidic protein (GFAP). In WB, Cx36 content in optic nerve was approximately halved when compared with retina (0.58 ± 0.005 in proximal stump and 0.44 ± 0.02 in distal stump), Cx45 showed higher levels (0.68 ± 0.01 in proximal stump and 0.9 ± 0.07 in distal stump). In immunogold-EM of optic nerve sections, we found electric synapses (formed mostly by Cx45) directly coupling neighbouring axons. In fVEP, blocking of gap junctions with meclofenamic acid resulted in significant prolongation of the latency of P1 wave up to 160% after 30 min (p < 0.001). Optic nerve (ON) axons are equipped with electrical synapses composed of neuronal connexins, especially Cx45, creating direct morphological and functional connections between each other. This finding could have substantial implications for understanding of the pathogenesis of various optic neuropathies and identifies a new potential target for a therapeutic approach.


Evidence-based morning report: a popular new format in a large teaching hospital.
Recent innovations in postgraduate medical education place greater emphasis on evidence-based curricula and self-directed, learner-centered education. Little has been published to date about how to apply these educational innovations to morning report, traditionally an important daily teaching venue in all internal medicine training programs. We describe here the content and conduct of a new evidence-based morning report at a large teaching hospital where it has become the popular hub for residents' self-directed academic activities. Methodologic standards are needed to study, report, and evaluate outcomes of similar educational interventions.


Long term results of primary radiosurgery for vestibular schwannomas.
Stereotactic radiosurgery (SRS) has become a primary option for management for both newly diagnosed vestibular schwannomas (VS), as well as VS that enlarge after initial observation. A retrospective review of our prospectively maintained data base found 871 patients who underwent Gamma knife® SRS as their initial (primary) management between 1987 and 2008. Follow-up ranged from 1-25 years (median = 5.2 years) Median tumor volume was 0.9 cc (0.02-36) and median margin dose was 13 Gy (12-25). Progression free survival (PFS) after SRS was 97% at 3 years, 95% at 5 years, and 94% at 10 years. Freedom from delayed surgical resection was found in 98.7% of patients. Smaller tumor volume was significantly associated with improved PFS. There were 326 patients with serviceable hearing (Gardner-Robertson 1 or 2) at the time of SRS with audiological follow-up of ≥ 1 year. Serviceable hearing preservation rates after SRS were 89.8% at 1 year, 76.9% at 3 years, 68.4% at 5 years, 62.5% at 7 years, and 51.4% at 10 years. Factors associated with improved serviceable hearing preservation included younger age, Gardner-Robertson grade 1 at SRS, and absence of subjective complaints of dysequilibrium or vertigo (vestibulopathy). Fifty-one patients (5.8%) developed trigeminal neuropathy. Fourteen (1.6%) developed a transient House-Brackmann grade 2 or 3 facial neuropathy. In this report with extended follow-up, primary SRS achieved tumor growth control in 94% of patients. Optimization of long- term cranial nerve outcomes remains an important achievement of this management strategy for VS.


Dietary glucosylceramide enhances cornified envelope formation via transglutaminase expression and involucrin production.
In this study, we investigated whether dietary glucosylceramide (GlcCer) and its metabolite sphingoid bases, sphingosine (SS), phytosphingosine (PS), sphingadienine (SD) and 4-hydroxysphingenine (4HS), influence cornified envelope (CE) formation. CE is formed during terminal differentiation of the epidermis through crosslinking of specific precursor proteins by transglutaminases (TGases), and is essential for the skin's barrier function. Oral administration of GlcCer (0.25 mg/day) for 14 consecutive days dramatically reduced transepidermal water loss, an indicator of the skin barrier condition, in hairless mice with barrier perturbation induced by single-dose ultraviolet B (UVB) irradiation. The GlcCer treatment also increased the level of TGase-1 mRNA in UVB-irradiated murine epidermis approximately 1.6-fold compared with the control. Further, all four sphingoid bases at 1 μM concentration enhanced CE formation of cultured normal human keratinocyte cells. Among them, SS, PS and SD, but not 4HS, stimulated production of involucrin, one of the CE major precursor proteins. SD increased the expression of TGase-1 mRNA, while SS increased the expression of TGase-3 mRNA. These results indicate that the skin barrier improvement induced by oral GlcCer treatment might be at least partly due to a reinforcement of CE formation in the epidermis mediated by sphingoid bases metabolically derived from GlcCer.


Anatomic basis for auditory brainstem implant.
Profound bilateral retrocochlear deafness cannot respond to a cochlear implant. For such patients only electrical stimulation of the cochlear nucleus complex can achieve, at best, a partial restoration of hearing. Based on the experience of the W.F. House group at the House Ear Institute in Los Angeles, we have developed an implantable device with many surface electrodes. A personal study has enabled us to establish the main relationships of the nucleus with the aim of inserting the device in contact with it, and to verify its effectiveness in the region. Histological study of anatomic specimens has shown the presence of spheroid neurone, considered to be the secondary neurone of the auditory pathway, at the level of the area of implantation.


TORC2 regulates hepatic insulin signaling via a mammalian phosphatidic acid phosphatase, LIPIN1.
TORC2 is a major transcriptional coactivator for hepatic glucose production. Insulin impedes gluconeogenesis by inhibiting TORC2 via SIK2-dependent phosphorylation at Ser171. Interruption of this process greatly perturbs hepatic glucose metabolism, thus promoting hyperglycemia in rodents. Here, we show that hyperactivation of TORC2 would exacerbate insulin resistance by enhancing expression of LIPIN1, a mammalian phosphatidic acid phosphatase for diacylglycerol (DAG) synthesis. Diet-induced or genetic obesity increases LIPIN1 expression in mouse liver, and TORC2 is responsible for its transcriptional activation. While overexpression of LIPIN1 disturbs hepatic insulin signaling, knockdown of LIPIN1 ameliorates hyperglycemia and insulin resistance by reducing DAG and PKCvarepsilon activity in db/db mice. Finally, TORC2-mediated insulin resistance is partially rescued by concomitant knockdown of LIPIN1, confirming the critical role of LIPIN1 in the perturbation of hepatic insulin signaling. These data propose that dysregulation of TORC2 would further exaggerate insulin resistance and promote type 2 diabetes in a LIPIN1-dependent manner.


Functional gain and speech understanding obtained by Vibrant Soundbridge or by open-fit hearing aid.
There is no significant difference in speech recognition scores obtained with the Vibrant Soundbridge and the open-fit hearing aid. However, the Vibrant Soundbridge may be superior to open-fit hearing aids in improving hearing at high frequencies (4-8 kHz). To assess whether an improvement in speech recognition conferred by Vibrant Soundbridge is more marked than that afforded by open-fit hearing aids in patients with sloping high frequency sensorineural hearing loss (SNHL). This study had a self-control prospective design. Seven patients aged 21-62 years with sloping high frequency SNHL were recruited into the study. Each patient received a Vibrant Soundbridge middle ear implant (Vibrant MED-EL) and wore an open-fit hearing aid (Danavox, DOT 10). Speech recognition tests were performed according to protocols suggested by árpád Götze's speech definition test in Hungarian language. In the first session, conventional hearing thresholds (unaided pure tone thresholds) were measured. In the second session, the aided sound-field threshold, speech understanding score and functional gain obtained using middle ear implants and open-fit hearing aids were determined after programming of the devices. Regarding speech recognition scores, there were no significant differences between data obtained with the middle ear implant and those with the open-fit hearing aid.


Percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma under C-arm cone beam CT guidance.
The aim of this study was to assess the feasibility, safety and efficacy of percutaneous radiofrequency ablation of lung metastases from colorectal carcinoma using C-arm cone beam computed tomography (CBCT) guidance. This single-center prospective observational study was performed from August 2013 to August 2016, and included consecutive patients referred for radiofrequency ablation of lung metastases from colorectal cancer. Radiofrequency ablation procedures were performed under C-arm CBCT guidance. Feasibility was assessed by probe accuracy placement, time to accurate placement and number of C-arm CBCT acquisitions to reach the target lesion. Safety was assessed by the report of adverse event graded using the common terminology criteria for adverse events (CTCAE-V4.0). Efficacy was assessed by metastases response rate using RECIST 1.1 and 18FDG-PET-CT tumor uptake at 6months. Fifty-four consecutive patients (32 men, 22 women) with a mean age of 63±8 (SD) years (range: 51-81years) with a total of 56 lung metastasis from colorectal metastases were treated in a single session. The mean tumor diameter was 25.6±4.5 (SD)mm (range: 17-31mm). Median time to insert the needle into the target lesion was 10min (range: 5-25min). Median number of needles repositioning and C-arm CBCT acquisition per patient was 1 (range: 0-3) and 4 (range: 3-6) respectively. The accuracy for radiofrequency ablation probe placement was 2±0.2 (SD)mm (range: 0-9mm). Pneumothorax requiring chest tube placement occurred in one patient (CTCAE-V4.0 grade 3). At 6months, all patients were alive with tumor response rate of -27% and had no significant activity on the 18FDG-PET CT follow-up. Percutaneous radiofrequency ablation of lung metastases from colorectal cancer under C-arm CBCT guidance is feasible and safe, with immediate and short-term results similar to those obtained using conventional CT guidance.


A facile strategy for reclaiming discarded graphite and harnessing the rate capabilities of graphite anodes.
Graphite negative electrodes are unbeaten hitherto in lithium-ion batteries (LiBs) due to their unique chemical and physical properties. Thus, the increasing scarcity of graphite resources makes smart recycling or repurposing of discarded graphite particularly imperative. However, the current recycling techniques still need to be improved upon with urgency. Herein a facile and efficient hydrometallurgical process is reported to effectively regenerate aged (39.5 %, 75 % state-of-health, SOH) scrapped graphite (SG) from end-of-life lithium-ion batteries. Ultimately, the first cycle reversible capacity of SG1 (SOH = 39.5 %) improved from 266 mAh/g to 337 mAh/g while 330 mAh/g (98 %) remain after 100 cycles at 0.5 C. The reversible capacity for the first cycle of SG2 (SOH = 75 %) boosted from 335 mAh/g to 366 mAh/g with the capacity retention of 99.3 % after 100 cycles at 0.5 C, which is comparable with the benchmark commercial graphite. The regenerated graphites RG1 and RG2 exhibit excellent output characteristics even increasing the rate up to 4 C. This is the best rate level reported in the literature to date. Finally, the diffusion coefficient of Li ions during deintercalation and intercalation in the regenerated graphites have been measured by galvanostatic intermittent titration technique (GITT), determining values 2 orders-of-magnitude higher than that of the spent counterparts. Taking advantage of the synergistic effect of acid leaching and heat treatment, this strategy provides a simple and up-scalable method to recycle graphitic anodes.


Auxin-responsive gene expression: genes, promoters and regulatory factors.
A molecular approach to investigate auxin signaling in plants has led to the identification of several classes of early/primary auxin response genes. Within the promoters of these genes, cis elements that confer auxin responsiveness (referred to as auxin-response elements or AuxREs) have been defined, and a family of trans-acting transcription factors (auxin-response factors or ARFs) that bind with specificity to AuxREs has been characterized. A family of auxin regulated proteins referred to as Aux/IAA proteins also play a key role in regulating these auxin-response genes. Auxin may regulate transcription on early response genes by influencing the types of interactions between ARFs and Aux/IAAs.


[Approach to a definition of mal-union callus after Pouteau-Colles fractures (author's transl)].
Sixty-four patients with a Pouteau-Colles fracture of the wrist were reviewed. Different aspects of mal-union are correlated with subsequent function. A suitable classification is proposed.


Remarkable impact of amino acids on ginsenoside transformation from fresh ginseng to red ginseng.
Amino acids are one of the major constituents in Panax ginseng, including neutral amino acid, acidic amino acid, and basic amino acid. However, whether these amino acids play a role in ginsenoside conversion during the steaming process has not yet been elucidated. In the present study, to elucidate the role of amino acids in ginsenoside transformation from fresh ginseng to red ginseng, an amino acids impregnation pretreatment was applied during the steaming process at 120°C. Acidic glutamic acid and basic arginine were used for the acid impregnation treatment during the root steaming. The ginsenosides contents, pH, browning intensity, and free amino acids contents in untreated and amino acid-treated P. ginseng samples were determined. After 2 h of steaming, the concentration of less polar ginsenosides in glutamic acid-treated P. ginseng was significantly higher than that in untreated P. ginseng during the steaming process. However, the less polar ginsenosides in arginine-treated P. ginseng increased slightly. Meanwhile, free amino acids contents in fresh P. ginseng, glutamic acid-treated P. ginseng, and arginine-treated P. ginseng significantly decreased during steaming from 0 to 2h. The pH also decreased in P. ginseng samples at high temperatures. The pH decrease in red ginseng was closely related to the decrease in basic amino acids levels during the steaming process. Amino acids can remarkably affect the acidity of P. ginseng sample by altering the pH value. They were the main influential factors for the ginsenoside transformation. These results are useful in elucidating why and how steaming induces the structural change of ginsenoside in P. ginseng and also provides an effective and green approach to regulate the ginsenoside conversion using amino acids during the steaming process.


Clinical and radiological effects of Corticosteroid injection combined with deep transverse friction massage and Mill's manipulation in lateral epicondylalgia-A prospective, randomized, single-blinded, sham controlled trial.
The knowledge about the effective implementation of corticosteroid injection (CS) with deep transverse friction massage (DTFM) and Mill's manipulation (MM) on clinical and radiological changes (Magnetic resonance imaging-MRI and Ultra sound) in lateral epicondylalgia (LE) is lacking. Therefore, the objective of this study is proposed to find and compare the effects of corticosteroid injection (CS) DTFM and Mill's manipulation on clinical and radiological changes in lateral epicondylalgia. Randomized, single-blinded, controlled study was conducted on 60 LE participants at university hospital. The active MM group (n = 30) received corticosteroid injection with DTFM and active Mill's manipulation (MM) three sessions a week for 4 weeks and the sham MM group received corticosteroid injection with sham manipulation. The primary outcome was pain intensity, measured with the visual analog scale. The other outcome measures were percentage of injury measured by MRI and ultrasound, functional disability, handgrip strength, patient perception, kinesiophobia, depression status and quality of life which were measured at 4 weeks, 8weeks and at 6 months follow up. The between-group difference in pain intensity at 4 weeks was 1.6 (CI 95% 0.97 to 2.22), which shows improvement in the active group than sham group. The similar effects have been noted after 8 weeks and at 6 months 2.0 (CI 95% 1.66 to 2.33) follow up in pain intensity. Similar improvements were also found on percentage of injury, functional disability, handgrip strength, patient perception, kinesiophobia, depression status and quality of life (p = 0.001). Corticosteroid injection with DTFM and Mill's manipulation was superior to sham group for improving pain, percentage of injury, functional disability, handgrip strength, patient perception, kinesiophobia, depression status and quality of life in people with lateral epicondylalgia. Clinical trial registration: CTRI/2020/05/025135 trial registered prospectively on 12/05/2020. https://trialsearch.who.int/Trial2.aspx?TrialID=CTRI/2020/05/025135.


Effect of synchronization of firings of different motor unit types on the force variability in a model of the rat medial gastrocnemius muscle.
The synchronized firings of active motor units (MUs) increase the oscillations of muscle force, observed as physiological tremor. This study aimed to investigate the effects of synchronizing the firings within three types of MUs (slow-S, fast resistant to fatigue-FR, and fast fatigable-FF) on the muscle force production using a mathematical model of the rat medial gastrocnemius muscle. The model was designed based on the actual proportion and physiological properties of MUs and motoneurons innervating the muscle. The isometric muscle and MU forces were simulated by a model predicting non-synchronized firing of a pool of 57 MUs (including 8 S, 23 FR, and 26 FF) to ascertain a maximum excitatory signal when all MUs were recruited into the contraction. The mean firing frequency of each MU depended upon the twitch contraction time, whereas the recruitment order was determined according to increasing forces (the size principle). The synchronization of firings of individual MUs was simulated using four different modes and inducing the synchronization of firings within three time windows (± 2, ± 4, and ± 6 ms) for four different combinations of MUs. The synchronization was estimated using two parameters, the correlation coefficient and the cross-interval synchronization index. The four scenarios of synchronization increased the values of the root-mean-square, range, and maximum force in correlation with the increase of the time window. Greater synchronization index values resulted in higher root-mean-square, range, and maximum of force outcomes for all MU types as well as for the whole muscle output; however, the mean spectral frequency of the forces decreased, whereas the mean force remained nearly unchanged. The range of variability and the root-mean-square of forces were higher for fast MUs than for slow MUs; meanwhile, the relative values of these parameters were highest for slow MUs, indicating their important contribution to muscle tremor, especially during weak contractions.


[Anti-inflammatory action of myoinositol in renal insufficiency].
Release of prostaglandin E2 (PGE2) and leukotrien B4 (LTB4) in vitro by resting and PHA-stimulated peripheral blood mononuclear cells (PBMNC) in the presence of three concentrations of myoinositol (30, 300, 600 micromol/l) was investigated. We examinated 10 uremic patients on regular hemodialysis treatment and 10 healthy subjects (control group). Release of PGE2 and LTB4 by resting and PHA-stimulated PBMNC was significantly lower in the presence of myoinositol in concentrations generally obserwed in the blood serum of chronic uraemic patients on regular hemodialysis treatment (600 micromol/l) in both investigated groups, while it remained unchanged in the presence of myoinositol in the concentration observed in normal blood serum (30 micromol/l). The results seem to indicate that myoinositol, in the concentrations found in uremic blood serum, may possibly exert antiinflammatory actions.


Prussian Blue acts as a mediator in a reagentless cytokinin biosensor.
An electrochemical biosensor for detection of the plant hormone cytokinin is introduced. Cytokinin homeostasis in tissues of many lower and higher plants is controlled largely by the activity of cytokinin dehydrogenase (CKX, EC 22.214.171.124) that catalyzes an irreversible cleavage of N(6)-side chain of cytokinins. Expression of Arabidopsis thaliana CKX2 from Pichia pastoris was used to prepare purified AtCKX2 as the basis of the cytokinin biosensor. Prussian Blue (PrB) was electrodeposited on Pt microelectrodes prior to deposition of the enzyme in a sol-gel matrix. The biosensor gave amperometric responses to several cytokinins. These responses depended on the presence of both the enzyme and the Prussian Blue. Thus Prussian Blue must act as an electron mediator between the FAD centre in CKX2 and the Pt surface.


The effect of polyunsaturated fatty acid deficiency on allergic response in ovalbumin-immunized mice.
Polyunsaturated fatty acids (PUFAs) are present in biological membranes and influence membrane fluidity and immune responses. PUFAs such as 18:2n-6 and 18:3n-3 cannot be synthesized de novo in mammals and are thus called essential fatty acids (EFAs). In addition, PUFAs can be converted to very long-chain PUFAs (VLC-PUFAs), such as arachidonic acid and docosahexaenoic acid, in the body. Although avoiding allergens is an effective strategy for food-allergy patients, the dietary exclusion of several allergens reportedly induces deficiencies in essential nutrients such as PUFAs. In this study, we investigated whether an EFA-deficient (EFAD) diet influenced allergic symptoms in ovalbumin (OVA)-immunized mice. Unexpectedly, no exacerbation of immune responses after OVA-sensitization was observed in mice fed an EFAD diet, and no differences in serum PUFA levels between OVA-immunized and non-immunized mice fed the EFAD diet were detected. However, levels of VLC-PUFAs in the small intestine increased after OVA-sensitization and did not decrease during EFAD diet administration, showing that small intestinal VLC-PUFAs levels were strongly preserved in the food-allergy model mice. Further studies are required to elucidate the mechanisms by which small intestinal VLC-PUFAs are retained in food-allergy model mice.


Clinical learning during the pandemic: Experiences of LPN-BN undergraduate nursing students.
When the COVID-19 pandemic was declared in March 2020, nursing programs made rapid decisions regarding clinical placement experiences for students. In many nursing programs, this meant ending clinical placements early, delaying clinical courses, and moving clinical courses to simulation. The purpose of this study was to explore LPN-BN students' experiences in clinical courses during the COVID-19 pandemic. A qualitative descriptive approach was employed in this study. Fifteen semi-structured conversational interviews with nursing students and recent graduates were conducted. Inductive content analysis was used to analyse the data. Four main concepts were identified: (1) logistics of learning; (2) shifts in clinical learning; (3) mental health matters; (4) readiness to practice. It is important to understand the experience of nursing students as this is an inordinately stressful and impressionable time for them. Insight into the student experience, will inform educators in the areas of curriculum and competency-based evaluation as well as supports for student mental health and well-being.


Daily changes in neuronal activities of the dorsal motor nucleus of the vagus under standard and high-fat diet.
Recently, we found that the dorsal vagal complex displays autonomous circadian timekeeping properties The dorsal motor nucleus of the vagus (DMV) is an executory part of this complex - a source of parasympathetic innervation of the gastrointestinal tract Here, we reveal daily changes in the neuronal activities of the rat DMV, including firing rate, intrinsic excitability and synaptic input - all of these peaking in the late day Additionally, we establish that short term high-fat diet disrupts these daily rhythms, boosting the variability in the firing rate, but blunting the DMV responsiveness to ingestive cues These results help us better understand daily control over parasympathetic outflow and provide evidence on its dependence on the high-fat diet ABSTRACT: The suprachiasmatic nuclei (SCN) of the hypothalamus function as the brain's primary circadian clock, but circadian clock genes are also rhythmically expressed in several extra-SCN brain sites where they can exert local temporal control over physiology and behaviour. Recently, we found that the hindbrain dorsal vagal complex possesses strong daily timekeeping capabilities, with the area postrema and nucleus of the solitary tract exhibiting the most robust clock properties. The possibility that the executory part of this complex - the dorsal motor nucleus of the vagus (DMV) - also exhibits daily changes has not been extensively studied. The DMV is the source of vagal efferent motoneurons that regulate gastric motility and emptying and consequently influence meal size and energy homeostasis. We used a combination of multi-channel electrophysiology and patch clamp recordings to gain insight into effects of time of day and diet on these DMV cells. We found that DMV neurons increase their spontaneous activity, excitability and responsiveness to metabolic neuromodulators at late day and this was paralleled with an enhanced synaptic input to these neurons. A high-fat diet typically damps circadian rhythms, but we found that consumption of a high-fat diet paradoxically amplified daily variation of DMV neuronal activity, while blunting the neurons responsiveness to metabolic neuromodulators. In summary, we show for the first time that DMV neural activity changes with time of day, with this temporal variation modulated by diet. These findings have clear implications for our understanding of the daily control of vagal efferents and parasympathetic outflow.


Successful implementation of new Swiss recommendations on breastfeeding of infants born to women living with HIV.
Swiss national recommendations advise, since end of 2018, supporting women with HIV who wish to breastfeed. Our objective is to describe the motivational factors and the outcome of these women and of their infants. mothers included in MoCHiV with a delivery between January 2019 and February 2021 who fulfilled the criteria of the "optimal scenario" (adherence to cART, regular clinical care, and suppressed HIV plasma viral load (pVL) of <50 RNA copies/ml) and who decided to breastfeed after a shared decision-making process, were approached to participate in this nested study and asked to fill-in a questionnaire exploring the main motivating factors for breastfeeding. Between January 9, 2019 and February 7, 2021, 41 women gave birth, and 25 decided to breastfeed of which 20 accepted to participate in the nested study. The three main motivational factors of these women were bonding, neonatal and maternal health benefits. They breastfed for a median duration of 6.3 months (range 0.7-25.7, IQR 2.5-11.1). None of the breastfed neonates received HIV post-exposure prophylaxis. There was no HIV transmission: 24 infants tested negative for HIV at least 3 months after weaning; one mother was still breastfeeding when we analyzed the data. As a result of a shared decision-making process, a high proportion of mothers expressed a desire to breastfeed. No breastfed infant acquired HIV. The surveillance of breastfeeding mother-infant pairs in high resource settings should be continued to help update guidelines and recommendations.


Flanking polyproline sequences inhibit beta-sheet structure in polyglutamine segments by inducing PPII-like helix structure.
Polyglutamine (poly(Q)) expansion is associated with protein aggregation into beta-sheet amyloid fibrils and neuronal cytotoxicity. In the mutant poly(Q) protein huntingtin, associated with Huntington's disease, both aggregation and cytotoxicity may be abrogated by a polyproline (poly(P)) domain flanking the C terminus of the poly(Q) region. To understand structural changes that may occur with the addition of the poly(P) sequence, we synthesized poly(Q) peptides with 3-15 glutamine residues and a corresponding set of poly(Q) peptides flanked on the C terminus by 11 proline residues (poly(Q)-poly(P)), as occurs in the huntingtin sequence. The shorter soluble poly(Q) peptides (three or six glutamine residues) showed polyproline type II-like (PPII)-like helix conformation when examined by circular dichroism spectroscopy and were monomers as judged by size-exclusion chromatography (SEC), while the longer poly(Q) peptides (nine or 15 glutamine residues) showed a beta-sheet conformation by CD and defined oligomers by SEC. Soluble poly(Q)-poly(P) peptides showed PPII-like content but SEC showed poorly defined, overlapping oligomeric peaks, and as judged by CD these peptides retained significant PPII-like structure with increasing poly(Q) length. More importantly, addition of the poly(P) domain increased the threshold for fibril formation to approximately 15 glutamine residues. X-ray diffraction, electron microscopy, and film CD showed that, while poly(Q) peptides with >or=6 glutamine residues formed beta-sheet-rich fibrils, only the longest poly(Q)-poly(P) peptide (15 glutamine residues) did so. From these and other observations, we propose that poly(Q) domains exist in a "tug-of-war" between two conformations, a PPII-like helix and a beta-sheet, while the poly(P) domain is conformationally constrained into a proline type II helix (PPII). Addition of poly(P) to the C terminus of a poly(Q) domain induces a PPII-like structure, which opposes the aggregation-prone beta-sheet. These structural observations may shed light on the threshold phenomenon of poly(Q) aggregation, and support the hypothesized evolution of "protective" poly(P) tracts adjacent to poly(Q) aggregation domains.


The effect of carbohydrates in milk on the absorption of calcium by postmenopausal women.
The purpose of this investigation was to determine if the presence of carbohydrate in milk, either lactose or its hydrolysis products, enhance the bioavailability of calcium (Ca) in milk. Two studies were performed. In study A, fractional Ca absorption was measured in 11 lactose-tolerant postmenopausal women after an oral dose of 47Ca-equilibrated milk formula containing no carbohydrate (NOCHO), lactose (LACTOSE), or an equivalent amount of glucose plus galactose (SUGAR); all participated in three absorption studies in random order. The NOCHO formula contained 10.0 g protein and 217 mg Ca from a combination of milk mineral and protein isolates; the LACTOSE and SUGAR formulae contained in addition 12 g lactose or 6 g glucose plus 6 g galactose, respectively. In study B, fractional Ca absorption was measured in five postmenopausal women after an oral dose of 47Ca-equilibrated skim milk (217 mg Ca) and lactase-treated milk, each with sufficient carbohydrate added to equal 12 g. For both studies, the increase in forearm radioactivity 4 and 8 hours after oral 47Ca administration relative to the increase observed after IV administration was used to estimate fractional Ca absorption. The addition of lactose but not glucose plus galactose to the NOCHO formula enhanced Ca absorption (p less than 0.05). Fractional absorption at 4 hours was 0.386 from the LACTOSE formula compared with 0.310 for both the NOCHO and SUGAR formulae. Those individuals with the lowest absorption in the absence of carbohydrate had the greatest increase with lactose. In contrast, Ca absorption was the same from skim milk as from lactase-treated skim milk (study B).(ABSTRACT TRUNCATED AT 250 WORDS)


Debates in psychoanalysis: A Latin American perspective.
While pluralism allows for the recognition of different psychoanalytic models, it still remains a challenge to build processes and arguments strong enough to resolve basic disagreements. The Three-Level Model constitutes a valuable tool to an open critical discussion among analysts of different theoretical orientations regarding a clinical material, by providing sources of evidence about patient transformations in an analytic process.


The ClpP protein, a subunit of the Clp protease, modulates ail gene expression in Yersinia enterocolitica.
Yersinia enterocolitica is a gastrointestinal pathogen of humans and animals. Ail is a 17kDa cell-surface protein that confers on Y. enterocolitica resistance to serum killing and the ability to attach to and invade cells in vitro. The ail gene of Y. enterocolitica is regulated by temperature and growth phase. In stationary phase, ail transcript is only detected when bacteria are grown at the host temperature of 37 degrees C. Our laboratory previously described a group of mini-Tn10 mutants, which expressed ail in stationary phase at 28 degrees C. In one of these mutants, DP5102::mini-Tn10 3-2, the mini-Tn 10 inserted into a gene encoding a protein with 90.3% identity to the ClpP protease subunit from Escherichia coli. Expression of ail in stationary phase at 28 degrees C was also derepressed in a directed Y. enterocolitica clpP mutant. Analysis of ail transcripts in the wild-type and clpP mutant strains indicated that there is a single start site of transcription of ail and that the effect of the clpP mutation was on the initiation of transcription at this site. Similar to E. coli, a clpX homologue was identified downstream of clpP. The Y. enterocolitica clpP gene complemented the clpP mutant phenotype, repressing the expression of both ail transcript levels and cell surface-expressed Ail protein. Thus, ClpP has a role in the modulation of ail transcription in Y. enterocolitica.


A modern web-based health promotion program for patients in Greece with diabetes 2 and obesity: an interventional study.
Health promotion programs are most beneficial in chronic diseases such as diabetes and morbid obesity, which can be positively affected by changes in attitudes, beliefs, and lifestyle. This study aimed to develop an internet-based modern Health Promotion model using interactive online applications through continuing education and participation. The goal was to positively impact knowledge, behavior, and quality of life for patients with obesity and/or diabetes. This is a prospective interventional study on patients with obesity or type 2 diabetes. Seventeen two patients who met the inclusion criteria were distributed randomly into two groups (control and intervention) from 2019 to 2021 in Greece. All the participants were given questionaries concerning quality of life anxiety and depression (HADS) attitudes and beliefs, knowledge about their condition and general questions to establish a baseline. A traditional health promotion model was followed for the control group. For participants in the intervention group, a web-based health promotion program was created according to the goals of the research. Participants were instructed to log on 1-2 times a week for 5-15 min, with the understanding that the research team would be monitoring their activities. The website included two knowledge games and personalized educational material based on their needs. The sample comprised 72 patients (36 in control and 36 in the intervention groups). The mean age was 47.8 years for the control group and 42.7 years for the intervention group (p = 0.293). Both study groups had a significant increase in knowledge score on diabetes (Control group:3,24, Intervention group 11,88 p < 0,001) and obesity (Control group:4,9, Intervention group 51,63 p < 0,001) along with a positive attitude score towards fighting obesity (Control group: 1,8, Intervention group 13,6 p < 0,001). Still, the overall change was more remarkable for the intervention group, as indicated by the significant interaction effect of the analysis. Anxiety was decreased only in the intervention group (Control group:0,11, Intervention group - 0,17 p < 0,005). Analysis for QOL during follow-up showed that Physical Health and Level of Independence was improved in both study groups but the degree of improvement was more significant in the intervention group (Control group 0,31,Intervention group 0,73 p < 0,001). Psychological Health was improved only in the intervention group, with better scores at 6 and 12 months compared to controls (Control group 0,28,Intervention group 1,42 p < 0,001). Furthermore, Social relationships were improved only in the intervention group (Control group 0,02, Intervention group 0,56 p < 0,001). The results of the present study showed that the participants in the intervention group showed significant improvement in knowledge, attitudes, and beliefs after using the internet as a learning tool. The intervention group also showed significantly reduced anxiety and depression arising from chronic illness. All of this resulted in an improved quality of life regarding physical Health, mental Health, and social relationships. Technology and online-based health promotion programs can revolutionize how we approach the prevention and management of chronic and terminal illnesses by improving accessibility, personalizing care, increasing engagement and motivation, improving data analysis, and disease management.


Unusual distribution of DNA methylation within the hTERT CpG island in tissues and cell lines.
The promoter region of the gene encoding the human telomerase reverse transcriptase (hTERT) is located in a CpG island and was shown to be regulated, at least in part, by DNA methylation. However, the observed correlation between hTERT methylation and gene expression was opposite to the general model of regulation by DNA methylation. We established a detailed mapping of methylcytosines at the CpG island (-1539 to +1732) surrounding the hTERT promoter in tissues and cell lines. In telomerase-positive samples, a methylation of all the CpG sites was observed for the hTERT promoter region (-500 to +1), whereas the exonic part (+1 to +450) revealed an unstable methylation pattern. Incomplete methylation of the proximal exon region could be necessary for, at least, a low level of hTERT transcription. In conclusion, hypermethylation of the CpG island plays a complex but essential role in the expression of hTERT in telomerase-positive cells.


Measles surveillance in Kashmir: A mixed methods study.
Measles surveillance serves as the means of monitoring program success. The quintessential purpose of measles surveillance is to identify gaps and garner effective public health responses to achieve measles elimination. There were two key objectives: (i) to conduct an in-depth review of the existing measles surveillance system in Kashmir and highlight its strengths and weaknesses and (ii) to assess the pattern of measles-containing vaccine (MCV1) coverage and MCV2 coverage among under-5 years children and describe the health-seeking patterns of suspected cases of measles. The mixed methods study was conducted in the Kashmir valley from March 2018 to March 2019. An explorative qualitative design was followed using individual face-to-face interviews with thirty-two (n = 32) different stakeholders from the state, district, medical block, and primary health center (PHC) levels. To complement the qualitative study, a quantitative survey was done in two districts, Srinagar and Ganderbal, which consist of 5 and 4 medical blocks, respectively. Among the suspected cases of measles, 52% had visited PHCs. Sixty-four suspected cases of measles (64) were immunized with two doses of MCV. None of the clinically suspected cases of measles were further investigated. In the qualitative analysis, five themes were generated viz, "measles surveillance description of Kashmir valley;" "factors affecting measles surveillance, perceptions, and experiences of stakeholders;" "barriers to measles surveillance;" "measles surveillance activities need to be intensified;" and "respondent recommendations for building an effective and sensitive measles surveillance system." The current measles surveillance system in Kashmir was not effectively functioning; case-based measles surveillance is not being done as per the WHO guidelines. There is a lack of planning, advocacy, awareness, and communication of measles surveillance among the stakeholders. The visible barriers in measles surveillance included lack of training, logistics, incentives, and monitoring by internal and external agencies.


Review article: diagnosis and treatment of Helicobacter: a 2002 updated review.
The year 2002 saw advances on many fronts in the study of Helicobacter and gastroduodenal disease. Several studies have confirmed endoscopy as a valuable management procedure with confirmation of the diagnostic utility of the rapid urease test and the description of a new formulation of the test, which is more rapid in giving a result. Serology has been re-confirmed as a useful investigation in selected populations. Some commercial kits for near patient testing have also been assessed and although generally regarded as less accurate than laboratory based tests some have shown acceptable accuracy. The recent exciting development in diagnostic serology is the availability of the faecal antigen test; further studies have confirmed its usefulness as recommended screening tests. There have been several studies demonstrating that a test and treat policy has a significant patient benefit, both economic and medical, although there is some doubt if eradication of Helicobacter leads to regression of atrophy and metaplasia. However, in low Helicobacter-prevalence areas the test and treat policy is being challenged as an effective management strategy. Further studies have shown that compliance with treatment regimens is an important determinant of successful eradication. Finally several new eradication regimens have been reported particularly for use in patients who have had previous unsuccessful eradication attempts.


Prognostic value of the dense middle cerebral artery sign in patients with acute ischemic stroke.
The presence of a dense appearance of the horizontal part of the middle cerebral artery (the "dense middle cerebral artery sign") was looked for on CT scans taken on admission in 90 consecutive patients with ischemic stroke in the carotid artery distribution. The outcome of the 14 patients with the sign was poorer than that of 76 patients without the sign (Odds ratio 4.3). We suggest that this sign could be a useful prognostic variable in the acute phase of an ischemic stroke.


Anti-adhesive signals are mediated via major histocompatibility complex class II molecules in normal and neoplastic human B cells: correlation with B cell differentiation stage.
We show that major histocompatibility complex (MHC) class II molecules on B cells transit signals which regulate adhesion in a negative manner. Engagement of MHC class II molecules with antibodies results in detachment of B cells previously bound to interferon-gamma-activated human umbilical cord venous endothelial cells. This process depends on metabolic energy, active signaling and protein tyrosine kinase activity. The adhesion pathway influenced by this signaling event is neuraminidase sensitive. The anti-adhesive signaling program is activated in B cell lines with a mature phenotype, e.g. normal B cells from spleen and tonsil. In contrast, cell lines with a pre-B cell phenotype and normal B cells from peripheral blood are refractory to MHC class II-mediated regulation of adhesion. These results extend to neoplastic cells from patients with lymphoproliferative diseases representing different stages of B cell maturation. These results suggest that MHC class II-mediated signals regulate B cell adhesion in a developmentally programmed fashion; this might have implications for clinical behavior of B cell malignancies.


Cystic fibrosis detection by means of a test-strip.
The effectiveness of meconium screening for albumin as an indication of cystic fibrosis is examined. BM-Test Meconium was applied to 69,000 investigations. In 60 positive tests, cystic fibrosis was confirmed later. No increased albumin content was observed in four cases of cystic fibrosis.


Glycation of β-lactoglobulin combined by sonication pretreatment reduce its allergenic potential.
β-lactoglobulin (β-Lg) was treated through different ultrasonic power and subsequently glycated with galactose to investigate its structural changes and immunological properties, and then evaluated by high-resolution mass spectrometry, enzyme-linked immunosorbent assay and basophil histamine release test. Ultrasonication combined with glycation (UCG) modification significantly reduced the IgE/IgG-binding capacity, and the release of β-hexosaminidase, histamine and interleukin-6, accompanied with changes in the secondary and tertiary structures. The decrease in the allergenicity of β-Lg depended not only on the glycation of K47, 60, 83, 91 and 135 within the linear epitopes, but also on the denaturation of conformational epitopes, which was supported by the glycation-induced alterations of the secondary and tertiary structures. This study confirmed that UCG modification is a promising method for decreasing the allergenic potential of allergic proteins, which is likely to develop a practical technology to produce hypo-allergenic milk.


Dermatology of the head and neck: skin cancer and benign skin lesions.
Skin lesions are extremely common, and early detection of dangerous lesions makes skin cancer one of the most highly curable malignancies. By simply becoming aware of common lesions and their phenotypic presentation, dental professionals are empowered to detect suspicious dermatologic lesions in unaware patients. This article serves as an introduction to skin cancer and benign skin lesions for dental professionals.


A novel method for fat suppression in RARE sequences.
Rapid acquisition relaxation-enhanced (RARE) sequences (Hennig et al., Magn. Reson. Med. 3, 823 (1986)) utilize one or several Carr-Purcell-Meiboom-Gill (CPMG) echo trains to sample a number of k-space lines each repetition time TR. The technique can rapidly generate multislice T2-weighted images which, as a rule, are strikingly similar in contrast to conventional T2-weighted spin-echo (SE) images. An exception to this rule is the appearance of very bright signal from fat in T2-weighted RARE images as compared to conventional T2-weighted SE images. To reduce this fat signal, we introduce a time delay, tau c, between the 90 degrees x and first 180 degrees y pulse of each echo train such that a phase angle of pi/2 develops between fat and the reference (water) line at echo maxima. The technique leads to single-acquisition fat suppression without the use of frequency-selective saturation pulses and concomitant loss of slices per TR. A Bloch equation analysis is used to identify two major mechanisms contributing to suppression of off-resonance spins such that w tau c = pi/2. Namely, the CPMG sequence becomes a CP sequence with no self-correction properties for imperfect 180 degrees pulses leading to enhanced signal decay, and the raw k-space data matrix become segmented into blocks alternately multiplied by +/- i, leading to signal dispersion following Fourier transformation.


The presence of 3-hydroxypropionate and 1,3-propanediol suggests an alternative path for conversion of glycerol to Acetyl-CoA.
In our recent study using [U-13C3]glycerol, a small subset of hamsters showed an unusual profile of glycerol metabolism: negligible gluconeogenesis from glycerol plus conversion of glycerol to 1,3-propanediol (1,3PDO) and 3-hydroxypropionate (3HP) which were detected in the liver and blood. The purpose of the current study is to evaluate the association of these unusual glycerol products with other biochemical processes in the liver. Fasted hamsters received acetaminophen (400 mg/kg; n = 16) or saline (n = 10) intraperitoneally. After waiting 2 h, all the animals received [U-13C3]glycerol intraperitoneally. Liver and blood were harvested 1 h after the glycerol injection for NMR analysis and gene expression assays. 1,3PDO and 3HP derived from [U-13C3]glycerol were detected in the liver and plasma of eight hamsters (two controls and six hamsters with acetaminophen treatment). Glycerol metabolism in the liver of these animals differed substantially from conventional metabolic pathways. [U-13C3]glycerol was metabolized to acetyl-CoA as evidenced with downstream products detected in glutamate and β-hydroxybutyrate, yet 13C labeling in pyruvate and glucose was minimal (p < 0.001, 13C labeling difference in each metabolite). Expression of aldehyde dehydrogenases was enhanced in hamster livers with 1,3PDO and 3HP (p < 0.05). Detection of 1,3PDO and 3HP in the hamster liver was associated with unorthodox metabolism of glycerol characterized by conversion of 3HP to acetyl-CoA followed by ketogenesis and oxidative metabolism through the TCA cycle. Additional mechanistic studies are needed to determine the causes of unusual glycerol metabolism in a subset of these hamsters.


Common and specific large-scale brain changes in major depressive disorder, anxiety disorders, and chronic pain: a transdiagnostic multimodal meta-analysis of structural and functional MRI studies.
Major depressive disorder (MDD), anxiety disorders (ANX), and chronic pain (CP) are closely-related disorders with both high degrees of comorbidity among them and shared risk factors. Considering this multi-level overlap, but also the distinct phenotypes of the disorders, we hypothesized both common and disorder-specific changes of large-scale brain systems, which mediate neural mechanisms and impaired behavioral traits, in MDD, ANX, and CP. To identify such common and disorder-specific brain changes, we conducted a transdiagnostic, multimodal meta-analysis of structural and functional MRI-studies investigating changes of gray matter volume (GMV) and intrinsic functional connectivity (iFC) of large-scale intrinsic brain networks across MDD, ANX, and CP. The study was preregistered at PROSPERO (CRD42019119709). 320 studies comprising 10,931 patients and 11,135 healthy controls were included. Across disorders, common changes focused on GMV-decrease in insular and medial-prefrontal cortices, located mainly within the so-called default-mode and salience networks. Disorder-specific changes comprised hyperconnectivity between default-mode and frontoparietal networks and hypoconnectivity between limbic and salience networks in MDD; limbic network hyperconnectivity and GMV-decrease in insular and medial-temporal cortices in ANX; and hypoconnectivity between salience and default-mode networks and GMV-increase in medial temporal lobes in CP. Common changes suggested a neural correlate for comorbidity and possibly shared neuro-behavioral chronification mechanisms. Disorder-specific changes might underlie distinct phenotypes and possibly additional disorder-specific mechanisms.


Protective effect of coenzyme Q10 on exercise-induced muscular injury.
The effect of coenzyme Q10 administration on exercise-induced muscular injury was examined in rats. Coenzyme Q10-treated and control rats were exercised by 90 min of downhill treadmill running. A part of the animals in both groups were killed immediately after exercise and the others were 40 h postexercise. After the exercise bout, serum creatine kinase and lactate dehydrogenase activities were elevated in the control rats, but not in the coenzyme Q10-treated rats. These enzyme activities in the latter increased to the similar level of the former 40 h postexercise. The muscle coenzyme Q10 content increased by the coenzyme Q10 treatment. These results suggest that the coenzyme Q10 treatment protected skeletal muscles against injury caused during exercise, but not against damage related with inflammatory processes after exercise.


[Formation of the fertilization membrane of the egg inArtemia salina].
The unfertilized egg ofArtemia salina is not covered with any extracellular structure. No special organelles are found in the sub-cortical plasma. From the moment of fertilization, a membrane is progressively secreted by the egg. The membranogenous substance is first seen as large granules in the smooth endoplasmic reticulum, presumably transformed within Golgi elements and extruded in vesicles liberated from the Golgi apparatus. Retained by a glycocoat or by contact with the fluid of the genital tract, it spreads out into a fertilization membrane, soon surrounding a perivitelline space. The process lasts till 1 1/2 h after fertilization.


The Bereavement Experience for Partners of Patients With Central Nervous System Tumors.
To describe the experience of caregivers who have lost a partner to a central nervous system (CNS) tumor. 8 bereaved partners of patients with CNS tumors enrolled in a dyadic, behavioral randomized controlled trial at a comprehensive cancer center in the southern United States. Participants took part in a semistructured qualitative interview to describe the experience of their partner's death. Descriptive exploratory analysis was used to identify themes emerging from the interviews. Themes identified from bereaved participants' experiences were related to caring for their partner, separating from their partner on patient death, and continuing without their partner following patient death. Bereaved partners of patients with CNS tumors described how difficult it was to experience the patient's health decline and feeling unprepared for the patient's death, regardless of advance notice. Interventions targeting caregiver distress to improve their experience prior to and following the patient's death are needed.


The case for plural PBL: an analysis of dominant and marginalized perspectives in the globalization of problem-based learning.
The globalization of problem-based learning (PBL) in health professions education has been both celebrated and criticized. Using a critical narrative review approach, underpinned by our archive of global PBL literature and a targeted literature search, we analyze these dominant global discourses of PBL in health professions education. More precisely, we explore what is missed when the globalization of PBL is theorized either as a positive consequence of standardization, or a problematic spread of Western educational ideals and values around the world. We make visible how two dominant global discourses, a universalist and culturalist discourse, have emerged in the global proliferation of PBL. We also discuss the limitations of the two discourses by demonstrating how they either ignore contextual and cultural diversity or see it as problematic. We then turn to a perspective that has been marginalized in the PBL literature that emphasizes the global origins of PBL, transcending the dichotomy between West and non-West. We make a case for relating to PBL as a plural construct in order to learn from the cultural and situational nuances of educational activities labeled PBL around the world. We argue that PBL as a singular and universal concept has no global future, yet versions of PBL may continue to thrive locally. Finally, we propose avenues for future research that may help elucidate the global and local values that underpin our curricula, as well as the socio-political factors that perpetuate neo-colonialist views and practices in the uptake and implementation of PBL approaches across the globe.


SARS-CoV-2 pandemic and repercussions for male infertility patients: A proposal for the individualized provision of andrological services.
The prolonged lockdown of health facilities providing non-urgent gamete cryopreservation-as currently recommended by many reproductive medicine entities and regulatory authorities due to the SARS-CoV-2 pandemic will be detrimental for subgroups of male infertility patients. We believe the existing recommendations should be promptly modified and propose that the same permissive approach for sperm banking granted for men with cancer is expanded to other groups of vulnerable patients. These groups include infertility patients (eg, azoospermic and cryptozoospermic) undergoing medical or surgical treatment to improve sperm quantity and quality, as well as males of reproductive age affected by inflammatory and systemic auto-immune diseases who are about to start treatment with gonadotoxic drugs or who are under remission. In both scenarios, the "fertility window" may be transitory; postponing diagnostic semen analysis and sperm banking in these men could compromise the prospects of biological parenthood. Moreover, we provide recommendations on how to continue the provision of andrological services in a considered manner and a safe environment. Our opinion is timely and relevant given the fact that fertility services are currently rated as of low priority in most countries.


Growth changes of collagen cross-linking, calcium, and water content in bone.
It has been claimed that the increase in the strength of growing bone is due to increased mineral content. The strength of collagen is based on intermolecular covalent cross-links, and it has also been proposed that cross-link changes increase bone strength. Measurements of the content of calcium, collagen, and water, as well as cross-link analyses, were performed on the tibial cortex of growing dogs. Within the age range studied (8-44 weeks), no changes in calcium content expressed as a percentage of dry bone weight were seen. Collagen content expressed as weight of hydroxyproline per dry bone weight showed a minor reduction during growth. However, water content decreased considerably up to an age of about 25 weeks, which implies a concomitant increase in the amount of bone material. Of the two cross-link main groups, reducible and nonreducible, it is only possible chemically to analyze the reducible. During the final part of the period of growth and mechanical maturation of the bones, the number of reducible cross-links decreases. This indicates a concomitant increase in the more stable nonreducible forms. The possible mechanical relevance of the chemical changes found during growth is discussed.


Nurses go above and beyond.
The nurses who cared for people injured in the Manchester Arena attack dug deep and pulled together just like we always do and will continue to do.


Coupled analysis of transcriptome and BCR mutations reveals role of OXPHOS in affinity maturation.
Antigen-activated B cells diversify variable regions of B cell antigen receptors by somatic hypermutation in germinal centers (GCs). The positive selection of GC B cells that acquire high-affinity mutations enables antibody affinity maturation. In spite of considerable progress, the genomic states underlying this process remain to be elucidated. Single-cell RNA sequencing and topic modeling revealed increased expression of the oxidative phosphorylation (OXPHOS) module in GC B cells undergoing mitoses. Coupled analysis of somatic hypermutation in immunoglobulin heavy chain (Igh) variable gene regions showed that GC B cells acquiring higher-affinity mutations had further elevated expression of OXPHOS genes. Deletion of mitochondrial Cox10 in GC B cells resulted in reduced cell division and impaired positive selection. Correspondingly, augmentation of OXPHOS activity with oltipraz promoted affinity maturation. We propose that elevated OXPHOS activity promotes B cell clonal expansion and also positive selection by tuning cell division times.


In Vitro Assessment of Guanylyl Cyclase Activity of Plant Receptor Kinases.
Cyclic nucleotides such as 3',5'-cyclic adenosine monophosphate (cAMP) and 3',5'-cyclic guanosine monophosphate (cGMP) are increasingly recognized as key signaling molecules in plants, and a growing number of plant mononucleotide cyclases, both adenylate cyclases (ACs) and guanylate cyclases (GCs), have been reported. Catalytically active cytosolic GC domains have been shown to be part of many plant receptor kinases and hence directly linked to plant signaling and downstream cellular responses. Here we detail, firstly, methods to identify and express essential functional GC domains of receptor kinases, and secondly, we describe mass spectrometric methods to quantify cGMP generated by recombinant GCs from receptor kinases in vitro.


Feed intake, milk production and metabolism of Holstein, Gyr and Girolando-F1 heifers with high body condition score during the transition period.
The transition period in taurine dairy cows is widely reported in the literature. However, little is known about the metabolism of zebu animals and their crossbreeding with taurine breeds during this phase. Considering the importance of these breeds in tropical and subtropical regions, this study aimed to evaluate the feed intake, milk production and hepatic metabolism in Holstein, Gyr and Girolando-F1 (½ Holstein × ½ Gyr) heifers presenting high body condition score (BCS) during the transition period (prepartum weeks -2 and -1 and postpartum weeks +1 and + 3). Twelve heifers of each genetic group were used, totaling 36 animals. Variables considered were blood metabolites related to liver function, dry matter intake (DMI), body condition score (BCS), body weight (BW), milk yield (MY), and fat and protein concentrations in milk. Gyr heifers had the lowest concentrations of paraoxonase in weeks -2 (43.13 U/mL), -1 (62.10 U/mL) and + 3 (77.89 U/mL), albumin in week -1 (3.07 g/dL), and the highest concentration of non-esterified fatty acids (NEFA) in weeks -2 (1.35 mmol/L) and -1 (1.19 mmol/L). β-hydroxybutyrate (BHB) and NEFA values were negatively correlated with prepartum DMI (-0.82 and -0.57, respectively), while paraoxonase was positively correlated to DMI (0.54). Gyr cows were more susceptible to inflammation despite having intermediate BCS and lower milk yield. Girolando-F1 animals showed the highest BCS among groups, although their hepatic metabolism had better results than Gyr cows. Holstein animals had lower lipomobilization and higher DMI and MY between breeds. These results suggest that the metabolism of zebu and crossbred cows does not react equally to the metabolism of Holstein cows concerning stress factors such as transition period and obesity. Therefore, the present study addresses an emerging theme that highlights the need for differentiated management during the transition period between the different breeds studied in order to ensure the maximum health and welfare of these animals.


Genomics of the critically endangered monotypic genus Sinopora: the plastome of S. hongkongensis (Lauraceae).
Sinopora hongkongensis is a critically endangered endemic tree species restricted to Hong Kong. Here we report its plastome sequence. The S. hongkongensis plastome was 158,612 bp in length, with a large single-copy (LSC) region of 89,405 bp and a small single-copy (SSC) region of 18,205 bp, separated by two inverted repeat (IR) regions of 25,498 bp. It contained 126 genes, including 89 coding genes, 29 tRNA genes, and 8 rRNA genes. The overall GC content was 39.0%, and 43.0%, 37.7%, and 34.0%, in the IRs, LSC, and SSC regions, respectively. A phylogenetic analysis combining a subset of Lauraceae plastomes with closely related outgroup families confirms the placement of S. hongkongensis in Lauraceae and explores relationships with other genera in the family.