Transplant surgery injury recruits recipient MHC class II-positive leukocytes into the kidney.
CD4 T cells, which are stimulated by the "indirect pathway" of antigen-presentation, participate in rejection. These T cells are sensitized by recipient major histocompatibility complex (MHC) class II-positive leukocytes that migrate into the transplant. Therefore, an important early step in rejection is the immigration of these recipient MHC class II-positive leukocytes into the renal transplant. The regulation of this early step is not understood. We now test the hypothesis that such leukocytes immigrate into the renal transplant in response to ischemic injury occurring during the transplant procedure. We transplanted Brown Norway (BN) kidneys into F1 Lewis/Brown Norway (L/BN) recipients. The F1 recipients are tolerant to the parental BN antigens, and any infiltration of recipient MHC class II-positive leukocytes results from injury occurring during transplantation surgery. In addition, ischemia/reperfusion injury was also induced by temporarily occluding the native renal arteries for 30 minutes. Transplanted kidneys and native kidneys, which suffered ischemia/reperfusion injury, were studied by immunohistochemistry on days 3, 7, 14, and 28 after surgery. Staining by the new monoclonal antibody (mAb) OX62 and antibodies to MHC class II identified dendritic cells. In addition, the following monoclonal antibodies identified: gamma/delta T cells, V65; B cells, OX33; cells that may be macrophages, dendritic cells, or dendritic cell precursors, ED1 (+) and OX62 (-); and recipient class II MHC, OX3. After transplantation, the serum creatinine increased to 4 mg/dl and then decreased, which was consistent with reversible injury during transplantation and the absence of rejection. We found that the injury of transplantation itself resulted in the infiltration of recipient MHC class II-positive leukocytes into the transplanted kidney. This infiltrate peaked at days 7 to 14 after surgery. The inflammation was peritubular and patchy and involved cortex and outer medulla. Double staining for OX62 and OX3 identified some of the infiltrating leukocytes as dendritic cells. Other recipient leukocytes were MHC class II positive, ED1 positive, and OX62 negative. We also found that MHC class II leukocytes, including dendritic cells, infiltrated native kidneys injured by ischemia/reperfusion injury. To our knowledge, this is the first demonstration that injury to the kidney during transplantation recruits recipient MHC class II-positive leukocytes into the kidney. Some of these leukocytes are dendritic cells.


Peripheral nerve injuries resulting from common surgical procedures in the lower portion of the abdomen.
Twenty-three patients had a painful ilioinguinal and/or iliohypogastric nerve entrapment syndrome following common surgical procedures in the lower portion of the abdomen (appendectomy, repair of inguinal hernia, and gynecologic procedures through transverse incision). The diagnostic triad of nerve entrapment after operation comprises (1) typical burning or lancinating pain near the incision that radiates to the area supplied by the nerve, (2) clear evidence of impaired sensory perception of the nerve, and (3) pain relieved by infiltration with anesthetic for local effects at the site where the two nerves leave the internal oblique muscle. Surgical repair of the scar with resection of the compromised nerve is the most effective treatment. Sixteen patients became symptom free after neurectomy, seven still suffer chronic pain in the scar.


An Accurate and Rapid System to Identify Play Patterns in Tennis using Video Recording Material: Break Point Situations as a Case Study.
The goal of this study was to present an accurate and rapid detection system to identify patterns in tennis, based on t-pattern analysis. As a case study, the break point situations in the final matches of the clay court tournaments played during the seasons 2011 and 2012 between the tennis players Novak Djokovic and Rafael Nadal were chosen. The results show that Nadal achieves a higher conversion rate with respect to Djokovic in the break point situations, independent of the outcome of the match. Some repetitive patterns of both players were revealed in break point circumstances. In long rally sequences (higher than seven hits), the Spanish player won more break points, both serving and receiving, as a result of unforced errors of his opponent's backhand. In medium rally sequences (between four and seven hits), other factors such as the type, direction or serve location have shown to play an important role in the outcome of the point. The study also reveals that Djokovic frequently commits double faults in these critical situations of the match. This is the first time that t-patterns have been used to analyze the sport of tennis. The technique is based on computer vision algorithms and video recording material to detect particular relationships between events and helps to discover the hidden mechanistic sequences of tennis players.


Vitamins and sleep: an exploratory study.
We analyzed archival data from an epidemiology study to test the association between vitamin use and sleep. Random digit dialing was used to recruit 772 people ranging in age from 20 to 98 for a study of people's sleep experience. These individuals completed a set of questionnaires about their sleep, health, and daytime functioning. Five hundred and nineteen of these participants had available vitamin use data. Home. Five hundred and nineteen people participated. Recruitment applied minimal screening criteria and no attempt was made to favor people with or without sleep disturbance. This survey included no intervention. Participants completed 2 weeks of sleep diaries and a set of questionnaires. Of particular salience to the present study, participants reported their vitamin use in listing all medications and nutritional supplements being used currently. For those individuals taking a multivitamin or multiple single vitamins, sleep diaries revealed poorer sleep compared to non-vitamin users in the number and duration of awakenings during the night. After controlling for age, ethnicity, and sex the difference in number of awakenings was still marginally significant. The rate of insomnia, conservatively defined, and consumption of sleep medication were also marginally significantly higher among individuals taking multi-/multiple vitamins compared to those not taking vitamins. Disturbed sleep maintenance was associated with multi-/multiple vitamin use. Five equally plausible explanations were advanced to explain this association including vitamins cause poor sleep, poor sleepers seek vitamins, and unidentified factors promote both poor sleep and vitamin use. These data are considered preliminary. Methodological characteristics of future studies were described that hold the promise of more clearly illuminating the association between vitamins and sleep.


Neurologic syndromes related to anti-GAD65: Clinical and serologic response to treatment.
Antibodies against glutamic acid decarboxylase 65 (anti-GAD65) are associated with a number of neurologic syndromes. However, their pathogenic role is controversial. Our objective was to describe clinical and paraclinical characteristics of anti-GAD65 patients and analyze their response to immunotherapy. Retrospectively, we studied patients (n = 56) with positive anti-GAD65 and any neurologic symptom. We tested serum and CSF with ELISA, immunohistochemistry, and cell-based assay. Accordingly, we set a cutoff value of 10,000 IU/mL in serum by ELISA to group patients into high-concentration (n = 36) and low-concentration (n = 20) groups. We compared clinical and immunologic features and analyzed response to immunotherapy. Classical anti-GAD65-associated syndromes were seen in 34/36 patients with high concentration (94%): stiff-person syndrome (7), cerebellar ataxia (3), chronic epilepsy (9), limbic encephalitis (9), or an overlap of 2 or more of the former (6). Patients with low concentrations had a broad, heterogeneous symptom spectrum. Immunotherapy was effective in 19/27 treated patients (70%), although none of them completely recovered. Antibody concentration reduction occurred in 15/17 patients with available pre- and post-treatment samples (median reduction 69%; range 27%-99%), of which 14 improved clinically. The 2 patients with unchanged concentrations showed no clinical improvement. No differences in treatment responses were observed between specific syndromes. Most patients with high anti-GAD65 concentrations (>10,000 IU/mL) showed some improvement after immunotherapy, unfortunately without complete recovery. Serum antibody concentrations' course might be useful to monitor response. In patients with low anti-GAD65 concentrations, especially in those without typical clinical phenotypes, diagnostic alternatives are more likely.


Understanding the Uptake of Nanomedicines at Different Stages of Brain Cancer Using a Modular Nanocarrier Platform and Precision Bispecific Antibodies.
Increasing accumulation and retention of nanomedicines within tumor tissue is a significant challenge, particularly in the case of brain tumors where access to the tumor through the vasculature is restricted by the blood-brain barrier (BBB). This makes the application of nanomedicines in neuro-oncology often considered unfeasible, with efficacy limited to regions of significant disease progression and compromised BBB. However, little is understood about how the evolving tumor-brain physiology during disease progression affects the permeability and retention of designer nanomedicines. We report here the development of a modular nanomedicine platform that, when used in conjunction with a unique model of how tumorigenesis affects BBB integrity, allows investigation of how nanomaterial properties affect uptake and retention in brain tissue. By combining different in vivo longitudinal imaging techniques (including positron emission tomography and magnetic resonance imaging), we have evaluated the retention of nanomedicines with predefined physicochemical properties (size and surface functionality) and established a relationship between structure and tissue accumulation as a function of a new parameter that measures BBB leakiness; this offers significant advancements in our ability to relate tumor accumulation of nanomedicines to more physiologically relevant parameters. Our data show that accumulation of nanomedicines in brain tumor tissue is better correlated with the leakiness of the BBB than actual tumor volume. This was evaluated by establishing brain tumors using a spontaneous and endogenously derived glioblastoma model providing a unique opportunity to assess these parameters individually and compare the results across multiple mice. We also quantitatively demonstrate that smaller nanomedicines (20 nm) can indeed cross the BBB and accumulate in tumors at earlier stages of the disease than larger analogues, therefore opening the possibility of developing patient-specific nanoparticle treatment interventions in earlier stages of the disease. Importantly, these results provide a more predictive approach for designing efficacious personalized nanomedicines based on a particular patient's condition.


Cleavage of poly(A)-binding protein by enterovirus proteases concurrent with inhibition of translation in vitro.
Many enteroviruses, members of the family Picornaviridae, cause a rapid and drastic inhibition of host cell protein synthesis during infection, a process referred to as host cell shutoff. Poliovirus, one of the best-studied enteroviruses, causes marked inhibition of host cell translation while preferentially allowing translation of its own genomic mRNA. An abundance of experimental evidence has accumulated to indicate that cleavage of an essential translation initiation factor, eIF4G, during infection is responsible at least in part for this shutoff. However, evidence from inhibitors of viral replication suggests that an additional event is necessary for the complete translational shutoff observed during productive infection. This report examines the effect of poliovirus infection on a recently characterized 3' end translational stimulatory protein, poly(A)-binding protein (PABP). PABP is involved in stimulating translation initiation in lower eukaryotes by its interaction with the poly(A) tail on mRNAs and has been proposed to facilitate 5'-end-3'-end interactions in the context of the closed-loop translational model. Here, we show that PABP is specifically degraded during poliovirus infection and that it is cleaved in vitro by both poliovirus 2A and 3C proteases and coxsackievirus B3 2A protease. Further, PABP cleavage by 2A protease is accompanied by concurrent loss of translational activity in an in vitro-translation assay. Similar loss of translational activity also occurs simultaneously with partial 3C protease-mediated cleavage of PABP in translation assays. Further, PABP is not degraded during infections in the presence of guanidine-HCl, which blocks the complete development of host translation shutoff. These results provide preliminary evidence that cleavage of PABP may contribute to inhibition of host translation in infected HeLa cells, and they are consistent with the hypothesis that PABP plays a role in facilitating translation initiation in higher eukaryotes.


Alteration of anion channel kinetics in wild-type and abi1-1 transgenic Nicotiana benthamiana guard cells by abscisic acid.
The influence of the plant water-stress hormone abscisic acid (ABA) on anion channel activity and its interaction with protein kinase and phosphatase antagonists was examined in stomatal guard cells of wild-type Nicotiana benthamiana L. and of transgenic plants expressing the dominant-negative (mutant) Arabidopsis abi1-1 protein phosphatase. Intact guard cells were impaled with double-barrelled micro-electrodes and membrane current was recorded under voltage clamp in the presence of 15 mM CsCl and 15 mM tetraethylammonium chloride (TEA-Cl) to eliminate K+ channel currents. Under these conditions, the free-running voltage was situated close to 0 mV (+9 +/- 6 mV, n = 18) and the membrane under voltage clamp was dominated by anion channel current (ICl) as indicated from tall current reversal near the expected chloride equilibrium potential, current sensitivity to the anion channel blockers 9-anthracene carboxylic acid and niflumic acid, and by its voltage-dependent kinetics. Pronounced activation of ICl was recorded on stepping from a conditioning voltage of -250 mV to voltages between -30 and +50 mV, and the current deactivated with a voltage-dependent halftime at more negative voltages (tau approximately equal to 0.3 sec at -150 mV). Challenge with 20 microM ABA increased the steady-state current conductance, gCl, near 0 mV by 1.2- to 2.6-fold and at -150 mV by 4.5- to sixfold with a time constant of 40 +/- 4 sec, and it slowed ICl deactivation as much as fourfold at voltages near -50 mV, introducing two additional voltage-sensitive kinetic components to these current relaxations. Neither the steady-state and kinetic characteristics of ICl nor its sensitivity to ABA were influenced by H7 or staurosporine, both broad-range protein kinase antagonists. However, the protein phosphatase 1/2A antagonist calyculin A mimicked the effects of ABA on gCl and current relaxations on its own and exhibited a synergistic interaction with ABA, enhancing ICl sensitivity to ABA three- to four-fold. Quantitatively similar current characteristics were recorded from guard cells of abi1-1 transgenic N. benthamiana, indicating that the abi1-1 protein phosphatase does not influence the anion current or its response to ABA directly. These results demonstrate that ABA stimulates ICl and modulates its voltage sensitivity. Furthermore, they show that ABA promotes ICl, either by introducing additional long-lived states of the channel or by activating a second anion channel with similar permeation characteristics but with a very long dwell time in the open state. Overall, the data are broadly consistent with the view that ABA action engenders coordinate control of ICl together with guard cell K+ channels to effect solute loss and stomatal closure.


A structural phase transition in NaTaOGeO(4) and its relation to phase transitions in titanite.
A structural phase transition from space-group symmetry P2(1)/c to C2/c is reported for NaTaOGeO(4) (NTGO). The critical temperature has been located at T(c) = 116 K, based on the appearance of sharp diffraction maxima at positions h + k = 2n + 1 of reciprocal space on cooling below this temperature. Strongly anisotropic diffuse scattering in sheets normal to [001] is observable for T > T(c) and persists up to ambient temperature. Similarities to phase transitions observed in other compounds of the titanite structure type are discussed. The symmetry properties of these phase transitions are reassessed on the basis of the structural data available. The primary order parameter is identified with the displacement of the transition metal cation M (M = Ta in NTGO) away from the centre of symmetry that it nominally occupies in the paraphase. The order parameter transforms as the Y(2)(-) representation. The anisotropic diffuse scattering is attributed to the one-dimensional correlation of local M displacements parallel to the direction of chains of trans-corner-sharing MO(6) octahedra. The critical temperatures of the isomorphous phase transitions in various titanite-type compounds depend linearly on the squared transition-metal displacement measured in the ordered P2(1)/c phase.


First detection of cutavirus DNA in stools of patients with rheumatic diseases in Guangzhou, China.
Cutavirus (CuV) is a novel protoparvovirus possibly associated with diarrhea and cutaneous T-cell lymphomas. Patients with rheumatic disease are immunosuppressed and may be more vulnerable to pathogenic viruses. A descriptive study was conducted among hospitalized patients with rheumatic diseases and individuals undergoing medical health check-ups between June 2019 and June 2022 in Guangzhou, China. Stool samples of subjects were tested for CuV DNA. Demographic and fecal examination data of patients were obtained from electronic medical records. A total of 505 patients with rheumatic diseases and 244 individuals who underwent medical health check-ups were included in the study. Of the patients with rheumatic disease, 5.74% [95% confidence interval (CI): 4.03%-8.12%] were positive for CuV DNA, while no individual in the medical health check-up group was positive, indicating a close correlation between CuV and rheumatic disease. Men and patients with rheumatoid arthritis or ankylosing spondylitis, according to the disease classification, were more susceptible to being infected with CuV (P < 0.01). After adjustments, being male remained the only significant factor, with an adjusted odd ratio (OR) of 4.4 (95% CI: 1.7-11.4, P = 0.002). Phylogenetic analysis of the CuV VP2 sequences showed three diverse clades, one of which was segregated to be a single branching independent of previously known sequences, which is possible a new genotype.


fMR-adaptation indicates selectivity to audiovisual content congruency in distributed clusters in human superior temporal cortex.
Efficient multisensory integration is of vital importance for adequate interaction with the environment. In addition to basic binding cues like temporal and spatial coherence, meaningful multisensory information is also bound together by content-based associations. Many functional Magnetic Resonance Imaging (fMRI) studies propose the (posterior) superior temporal cortex (STC) as the key structure for integrating meaningful multisensory information. However, a still unanswered question is how superior temporal cortex encodes content-based associations, especially in light of inconsistent results from studies comparing brain activation to semantically matching (congruent) versus nonmatching (incongruent) multisensory inputs. Here, we used fMR-adaptation (fMR-A) in order to circumvent potential problems with standard fMRI approaches, including spatial averaging and amplitude saturation confounds. We presented repetitions of audiovisual stimuli (letter-speech sound pairs) and manipulated the associative relation between the auditory and visual inputs (congruent/incongruent pairs). We predicted that if multisensory neuronal populations exist in STC and encode audiovisual content relatedness, adaptation should be affected by the manipulated audiovisual relation. The results revealed an occipital-temporal network that adapted independently of the audiovisual relation. Interestingly, several smaller clusters distributed over superior temporal cortex within that network, adapted stronger to congruent than to incongruent audiovisual repetitions, indicating sensitivity to content congruency. These results suggest that the revealed clusters contain multisensory neuronal populations that encode content relatedness by selectively responding to congruent audiovisual inputs, since unisensory neuronal populations are assumed to be insensitive to the audiovisual relation. These findings extend our previously revealed mechanism for the integration of letters and speech sounds and demonstrate that fMR-A is sensitive to multisensory congruency effects that may not be revealed in BOLD amplitude per se.


PCR analysis of the distribution of unicellular cyanobacterial diazotrophs in the Arabian Sea.
An oligonucleotide primer, NITRO821R, targeting the 16S rRNA gene of unicellular cyanobacterial N2 fixers was developed based on newly derived sequences from Crocosphaera sp. strain WH 8501 and Cyanothece sp. strains WH 8902 and WH 8904 as well as several previously described sequences of Cyanothece sp. and sequences of intracellular cyanobacterial symbionts of the marine diatom Climacodium frauenfeldianum. This oligonucleotide is specific for the targeted organisms, which represent a well-defined phylogenetic lineage, and can detect as few as 50 cells in a standard PCR when it is used as a reverse primer together with the cyanobacterium- and plastid-specific forward primer CYA359F (U. Nubel, F. Garcia-Pichel, and G. Muyzer, Appl. Environ. Microbiol. 63:3327-3332, 1997). Use of this primer pair in the PCR allowed analysis of the distribution of marine unicellular cyanobacterial diazotrophs along a transect following the 67 degrees E meridian from Victoria, Seychelles, to Muscat, Oman (0.5 degrees S to 26 degrees N) in the Arabian Sea. These organisms were found to be preferentially located in warm (>29 degrees C) oligotrophic subsurface waters between 0 and 7 degrees N, but they were also found at a station north of Oman at 26 degrees N, 56 degrees 35'E, where similar water column conditions prevailed. Slightly cooler oligotrophic waters (<29 degrees C) did not contain these organisms or the numbers were considerably reduced, suggesting that temperature is a key factor in dictating the abundance of this unicellular cyanobacterial diazotroph lineage in marine environments.


Mechanical properties and microstructure of frozen carrots during storage as affected by blanching in water and sugar solutions.
Raw carrots and carrots blanched in water and in 4% trehalose and maltose solutions at 75°C for 3 (A) and 10 min (C) and at 90°C for 3 (B) and 10 min (D) were frozen and stored at -18°C for eight months. The effects of heating conditions and exogenous added sugars on the mechanical properties and microstructure of the vegetable after blanching and during frozen storage were studied. By scanning electron microscopy (SEM) analysis no significant differences were observed among samples A and B water-blanched and raw carrot while a thermo-protective effect due to the sugars addition was evidenced in sample D, undergone to the most severe thermal treatment. Freezing and frozen storage determined several fractures on both raw and blanched carrots due to ice crystals formation and re-crystallisation. The cryo-protective effect of the sugars on the vegetable microstructure was observed only in the 'over-blanched' sample D. The mechanical properties of carrots were affected by blanching which caused a hardness decrease but after freezing and one month of frozen storage, all samples showed a further dramatic reduction of hardness. Only samples characterised by a pectinesterase residual activity showed a softening also after one month of frozen storage likely for a competitive effect of the thermo-protective ability of trehalose on this enzyme. The exogenous trehalose was able to limit the hardness loss of carrots undergone to B, C and D blanching pre-treatments.


Categorization of free-text drug orders using character-level recurrent neural networks.
Manual annotation and categorization of non-standardized text ("free-text") of drug orders entered into electronic health records is a labor-intensive task. However, standardization is required for drug order analyses and has implications for clinical decision support. Machine learning could help to speed up manual labelling efforts. The objective of this study was to analyze the performance of deep machine learning methods to annotate non-standardized text of drug order entries with their therapeutically active ingredients. The data consisted of drug orders entered 8/2009-4/2014 into the electronic health records of inpatients at a large tertiary care academic medical center. We manually annotated the most frequent order entry patterns with the active ingredient they contain (e.g. "Prograf"⟵"Tacrolimus"). We heuristically included additional orders by means of character sequence comparisons to augment the training dataset. Finally, we trained and employed character-level recurrent deep neural networks to classify non-standardized text of drug order entries according to their active ingredients. A total of 26,611 distinct order patterns were considered in our study, of which the top 7.6% (2028) had been annotated with one of 558 distinct ingredients, leaving 24,583 unlabeled observations. Character-level recurrent deep neural networks achieved a Mean Reciprocal Rank (MRR) of 98% and outperformed the best representative baseline, a trigram-based Support Vector Machine, by 2 percentage points. Character-level recurrent deep neural networks can be used to map the active ingredient to non-standardized text of drug order entries, outperforming other representative techniques. While machine learning might help to facilitate categorization tasks, still a considerable amount of manual labelling and reviewing work is required to train such systems.


Comparison of Clinical and Radiographic Outcomes Between Central and Lateral Lesions After Osteochondral Autograft Transplantation for Osteochondritis Dissecans of the Humeral Capitellum.
Clinical studies have reported satisfactory results after osteochondral autograft transplantation (OAT) for central lesions of unstable osteochondritis dissecans (OCD) of the elbow. However, the outcomes after OAT for lateral lesions remain unclear. The clinical outcomes of OAT would be better for central lesions than for lateral lesions. Cohort study; Level of evidence, 3. The authors retrospectively evaluated 103 juvenile athletes (mean age, 13.2 years; range, 11-16 years) who underwent OAT for symptomatic OCD of the humeral capitellum from 2003 to 2014. Sixteen patients were excluded because they did not fit the inclusion criteria. The final cohort of 87 patients was divided by lesion type into central lesion (n = 43) and lateral lesion (n = 44) groups. When possible, a single large plug was created for grafting and trimmed to reconstruct the rounded joint surface. The clinical, radiographic, and magnetic resonance imaging outcomes were evaluated for each group at a mean follow-up of 43 months (range, 24-100 months). There were no significant differences in the age, sex, height, weight, duration of symptoms, follow-up time, preoperative range of motion, or Timmerman and Andrews score between the 2 groups. The preoperative osteoarthritic changes (0 of 43 for central vs 5 of 44 cases for lateral; P = .023), mean lesion size (12.2 ± 2.9 vs 18.2 ± 7.0 mm; P < .001), and graft number (1.6 vs 2.8; P < .001) were significantly greater in the lateral group versus the central group. The mean range of extension (2.3° ± 5.4° vs -3.2° ± 8.7°; P < .001) and Timmerman and Andrews score (194 vs 185; P = .006) at the final follow-up were significantly better for patients in the central group. More patients in the lateral group had postoperative radial head subluxation (0 of 43 vs 6 of 44; P = .012) and osteoarthritic changes (1 of 43 vs 9 of 44; P = .008). The mean MOCART score showed no significant differences between the groups (78.0 ± 15.7 vs 72.6 ± 20.9; P = .181). The rate of return to sports at the previous level was 100% in the central group and 86% in the lateral group ( P = .012). The clinical and radiographic outcomes after OAT associated with unstable OCD of the humeral capitellum were better for central lesions than for lateral lesions. However, satisfactory outcomes and a high rate of return to sports were obtained for unstable lateral lesions after OAT.


Acute hepatic necrosis induced by Brucells infection in hyperthyroid mice.
When small numbers of Brucella melitensis were inoculated into ABC mice, occasional hepatic granulomas without necrosis were demonstrated. The greatest multiplication of brucellae was detected in the spleens. Because it had been previously observed that ACTH or cortisone markedly accelerated the multiplication of brucellae in the livers of infected mice with destruction of liver cells, it was considered that triiodothyronine might likewise exaggerate a brucella infection by stimulating endogenous adrenal secretion. Although adrenal hypertrophy was produced, infection of mice treated with triiodothyronine resulted in severe hepatic necrosis or infarcts without the multiplication of brucellae in either the livers or spleens. The lesions were not encountered in untreated infected mice or in control mice treated with triiodothyronine. The necrosis was associated with minimal inflammatory reaction. The necrosis was not induced in mice treated with triiodothyronine and given brucella endotoxin. The precise genesis of the acute hepatic necrosis cited in these experiments remains undefined. Triiodothyronine did not cause deaths in mice infected with Br. melitensis. The infection was neither enhanced nor suppressed.


Inflammation, cognitive dysfunction, and suicidal ideation among patients with major depression.
Dysregulated proinflammatory cytokines have been shown to be associated with suicidal behavior. Cognitive deficits in working memory and inhibitory control have been demonstrated in depressed patients and people with suicidal ideation (SI). However, the association between proinflammatory cytokines, SI, and cognitive deficits in patients with major depressive disorder (MDD) remains unclear. A total of 77 patients with MDD and age-/sex-matched 60 healthy individuals were recruited. MDD patients were divided into two groups: with SI (n = 36) and no SI (n = 41). SI was defined by a score of ≥2 in item 3 of the 17-item Hamilton Rating Scale for Depression. Levels of proinflammatory cytokines, including soluble interleukin-6 receptor, soluble tumor necrosis factor-α receptor type 1, and C-reactive protein (CRP), were measured, and cognitive function was assessed using 2-back task and Go/No-Go task. Patients with SI had higher levels of CRP than those without SI and controls (P = .007). CRP was positively associated with SI (β = 0.21, P = .037), independent of cognitive function and depressive symptoms. Furthermore, SI was associated with cognitive deficits in working memory and inhibitory control after adjusting for confounding factors (P < .05). Our findings suggest that higher levels of serum CRP and deficits in working memory and inhibitory control may be associated with higher SI among patients with MDD.


Percutaneous Vertebroplasty for Primary Non-Hodgkin's Lymphoma of the Thoracic Spine: Case Report and Review of the Literature.
Primary non-Hodgkin's lymphoma of the vertebra is rare in the spine of the elderly. The clinical presentation and radiological features are unspecific, which make it more difficult for diagnosis. We report a case of a 79-year-old woman complaining of serious backache without any injury. The magnetic resonance imaging (MRI) showed invasion of the fifth thoracic vertebra with the posterior vertebral body wall defect. There was a high suspicion that the patient had a metastatic tumor of the vertebra. A percutaneous vertebroplasty was performed under fluoroscopic guidance, which was used to treat the osteoporotic vertebral compression fracture, vertebral metastases, verte-bral hemangioma, and multiple myeloma. The pain was rapidly and conspicuously relieved after the procedure. The visual analog scale (VAS) score decreased from 8 preoperatively to 2 postoperatively. The imaging examination postoperatively revealed a small amount cement leaking into the spinal canal, but there were no symptoms and no complications in our patient. During vertebroplasty, a biopsy was done by biopsy needle before injection of the cement (polymethyl methacrylate). The histopathological examination revealed a diffuse large B-cell lymphoma. No new evidence of any other lesion was found during a 6-month follow-up period. The patient was diagnosed with primary bone lymphoma finally. Due to the previous condition of the patient, R-miniCHOP chemotherapy was applied following the surgery in the department of hematology. Until the 9 months follow-up, the clinical result was still satisfactory. Vertebroplasty, polymethyl methacrylate, biopsy, spine, lymphoma, large B-cell, diffuse.


Layer-by-layer electrostatic deposition of biomolecules on surfaces for molecular recognition, redox mediation and signal generation.
Layer-by-layer supramolecular structures composed of alternate layers of negatively charged enzymes and cationic redox polyelectrolyte have been assembled. Glucose oxidase (GOx), lactate oxidase (LOx) and soybean peroxidase (SBP) have been electrically wired to the underlying electrode by means of poly(allylamine) with [Os(bpy)2ClPyCOH]+ covalently attached (PAA-Os) in organized structures with high spatial resolution. Biotinylated glucose oxidase has also been used to assemble step-by-step on antibiotin goat immunoglobulin (IgG) layers and the enzyme was electrically wired by PAA-Os. These spatially organized multilayers with mono- and bienzymatic schemes can work efficiently in molecular recognition, redox mediation and generation of an electrical signal. The concentration of redox mediator integrated into the multilayers, obtained from the voltammetric charge and an estimation of the layer thickness, exceeds by 100-fold the amount of deposited enzyme assessed by quartz crystal microbalance. Differences in GOx electrical wiring efficiency have been detected with the different assembling strategies. The surface concentration of electrically wired enzyme represents a small proportion of all the enzyme molecules present in the multilayers which can be oxidized by the soluble mediator [Os(bpy)2Cl PyCOOH]Cl. This proportion, as well as the rate of FADH2 oxidation by PAA-Os, increases with the number of electrically wired enzyme layers and with the spatial accessibility of the Os moiety to the enzyme active center.


The critical care nurse's role in end-of-life care: issues and challenges.
The purpose of this article is to discuss the challenges critical care nurses face when looking after patients needing End-of-Life (EoL) care in critical care environments. Critical care nurses frequently provide care to patients who fail to respond to treatments offered to support and prolong life. The dying phase for individuals in critical care settings, commonly after withholding/withdrawing treatment, is very short posing great demands on critical care nurses to provide physical and emotional support to both patients and their families. Despite the existence of recognized care planning frameworks that may help nurses in providing EoL care, these are not used by all units and many nurses rely on experience to inform practice. A number of aspects such as communication, patient/family-centred decision-making, continuity of care, emotional/spiritual support and support for health professionals have been indicated as contributing factors towards the provision of effective EoL care. These are considered from the perspective of critical care nursing. Skills development in key aspects of care provision may improve the provision of EoL care for critical care patients and their families. Critical care nurses have an essential role in the provision of effective EoL care; however, this dimension of their role needs further exploration. It is noted that educational opportunities need to be provided for critical care nurses to increase the knowledge on planning and delivering EoL care. To inform this evaluation of current EoL care provision in critical care is necessary to address a knowledge deficit of the needs of nurses who seek to support patients and their families at a critical time.


The temporal response and mechanism of action of tranexamic acid in endothelial glycocalyx degradation.
The endothelial glycocalyx (GCX) plays an important role in vascular barrier function. Damage to the GCX occurs due to a variety of causes including hypoxia, ischemia-reperfusion, stress-related sympathoadrenal activation, and inflammation. Tranexamic acid (TXA) may prevent GCX degradation. The therapeutic window for TXA administration and the mechanism of action has been under review. Membrane-anchored proteases (sheddases) are key components in endothelial cell biology including the regulation of vascular permeability. The effect of TXA administration on stress-related GCX damage, and the role of sheddases in this process was studied in a cell-based model. Confluent human umbilical vein endothelial cells (HUVEC) were exposed to hydrogen peroxide and/or epinephrine (EPI) to stimulate postshock reperfusion. TXA was added at various times after hydrogen peroxide (H2O2) and/or EPI exposure. GCX degradation was indexed by syndecan-1 and hyaluronic acid release. Activation of endothelial sheddases was indexed by A Disintegrin and Metalloproteinase-17 and matrix metalloproteinase-9 activity in culture supernatants. Exposure of HUVEC to either/both EPI and H2O2 resulted in a cellular stress and GCX disruption demonstrated by increased levels of syndecan-1 shedding, hyaluronic acid release, tumor necrosis factor-α release. Shedding of these GCX components was associated with increased activity of both A Disintegrin and Metalloproteinase-17 and matrix metalloproteinase. Disruption of the GCX was further demonstrated via fluorescent imaging, which demonstrated disruption after exposure to either/both H2O2 and EPI. Early administration of either TXA or doxycycline resulted in preservation of the GCX. Late administration of TXA had no effect, whereas doxycycline had some residual protective effect. Tranexamic acid as a serine protease inhibitor prevented GCX degradation via inhibition of endothelial sheddase activation. This effect was not apparent when TXA was administered greater than 60 minutes after "simulated" reperfusion. Our study supports the clinical practice of early TXA administration in the severely injured patient.


Identification of parthenogenesis-inducing effector proteins in Wolbachia.
Bacteria in the genus Wolbachia have evolved numerous strategies to manipulate arthropod sex, including the conversion of would-be male offspring to asexually reproducing females. This so-called "parthenogenesis-induction" phenotype can be found in a number of Wolbachia strains that infect arthropods with haplodiploid sex determination systems, including parasitoid wasps. Despite the discovery of microbe-mediated parthenogenesis more than 30 years ago, the underlying genetic mechanisms have remained elusive. We used a suite of genomic, computational, and molecular tools to identify and characterize two proteins that are uniquely found in parthenogenesis-inducing Wolbachia and have strong signatures of host-associated bacterial effector proteins. These putative parthenogenesis-inducing proteins have structural homology to eukaryotic protein domains including nucleoporins, the key insect sex-determining factor Transformer, and a eukaryotic-like serine-threonine kinase with leucine rich repeats. Furthermore, these proteins significantly impact eukaryotic cell biology in the model, Saccharomyces cerevisiae . We suggest these proteins are parthenogenesis-inducing factors and our results indicate this would be made possible by a novel mechanism of bacterial-host interaction.


Corneal Topographical Changes After Müller's Muscle-conjunctival Resection Surgery.
To evaluate corneal refractive and topographical changes after Müller's muscle conjunctival resection surgery on patients with mild ptosis. A total of 28 eyes of 28 patients with mild ptosis underwent Müller's muscle conjunctival resection. Visual acuity, margin reflex distance, and cycloplegic refraction were analyzed preoperatively and at first, third, and sixth months postoperatively. Change in corneal topography was analyzed with Sirius System using parameters including corneal astigmatism (CYL), average simulated keratometry value (simK), apical keratometry front (AKf), symmetry index front (SIf), and central corneal thickness (CCT) at the same intervals. Best-corrected visual acuity and cycloplegic refraction did not change significantly at all controls postoperatively. The mean change in corneal astigmatism, simK, SIf, and CCT did not show significant differences. Apical keratometry front showed a significant decrease at 3 and 6 months. The pressure of upper eyelid in patients with ptosis appeared to have resulted in steepening of the superior cornea along this axis. The surgical correction of ptosis induces flattening of superior cornea as shown by significant decrease in apical keratometry front value postoperatively and restores corneal topography to a more regular state.


Inhibition of protein synthesis: a basis for tunicamycin-induced decrease in rat liver cytochrome P-450.
Tunicamycin caused a dose and time dependent decrease in cytochrome P-450 in rat liver. A dose of 50 micrograms/kg caused a decrease of about 50% in 72 hours. A similar decrease in the activities of rat liver microsomal aniline hydroxylase, aminopyrine N-demethylase and ethoxycoumarin O-deethylase were also seen after the tunicamycin treatment. Tunicamycin also suppressed food and water intake but the decrease in cytochrome P-450 was not related to these effects. NADPH cytochrome c reductase was not markedly decreased by tunicamycin. A decrease in cytochrome P-450 was also observed in cultured rat hepatocytes treated with tunicamycin. It decreased incorporation of [35S]-methionine into total proteins as well as into various cytochrome P-450 isozymes of rat hepatocytes. This indicates that a decrease in protein synthesis may be responsible for the tunicamycin-induced decrease in cytochrome P-450 and drug metabolism.


Real-World Experience of Holmium Laser Enucleation of the Prostate with Patients on Anticoagulation Therapy.
Background: Holmium laser enucleation of the prostate (HoLEP) is a highly effective procedure for benign prostatic hyperplasia that is size independent and has been recommended for patients necessitating antiplatelet (AP) and anticoagulant (AC) medications. Although HoLEP is feasible in AP/AC patients, there is a lack of published results on real-world outcomes of patients on AP/AC therapy undergoing HoLEP. Patients and Methods: We performed a retrospective review of our institutional HoLEP database of demographics, perioperative and postoperative data, and outcomes of patients on AP and AC therapy compared with none. We also further stratified patients on warfarin compared with direct oral anticoagulants (DOACs). Results: Of 472 patients who underwent HoLEP at our institution from July 2018 to December 2019 with data on AP/AC drugs, 30 (6.3%) were on AP and 65 (17.2%) were on AC. One patient continued AP (3.3%), six patients (9.2%) were bridged on AC, and one patient (1.5%) continued AC through the time of HoLEP at the discretion of the prescribing provider. Preoperatively, only age was significantly different among the three groups (p < 0.001). There were no intraoperative differences. Postoperatively, there was a higher 90-day complication rate in AP and AC groups (p = 0.035), but not an increase in emergency department (ED) visits (p = 0.557) or Clavien ≥3 complications (p = 0.16). In comparison of patients on warfarin with DOAC, there was a lower rate of successful voiding trial (p = 0.009), higher 90-day complications (p = 0.003), and more ED visits (p = 0.003) in the warfarin group. Conclusions: HoLEP is safe and effective for patients who require AP or AC therapy. There is no increase in serious complications or worsened postoperative voiding parameters. Of patients on AC, those on DOAC have better outcomes compared with warfarin.


[Unexpected hemorrhage in surgery].
Unexpected hemorrhage in surgery may be avoided whenever preoperative examinations have not detected a defect of hemostasis. A prospective study conducted before oral surgery demonstrated that a simple preoperative screening program was suitable for specific detection of patients with bleeding tendencies and to indicate the need for a more detailed evaluation of hemostasis. The screening program includes a detailed history with the aim of detecting congenital defects of hemostasis or bleeding tendencies due to prolonged, acquired disorders. The thromboplastin time (Quick test) should be performed to evaluate asymptomatic, acquired coagulation defects, especially liver disease, whereas the semiquantitative determination of platelets on blood smears is necessary to rule out thrombocytopenia. A dramatic complication of massive bleeding is the so-called "dilution syndrome" caused by simultaneous blood loss and transfusion of stored blood (or red cells alone), leading to a progressive reduction of clotting factors and platelets. Therapeutic and organizational measures which are necessary in this exceptional situation are briefly discussed.


[Is it appropriate to consider wood preservative poisoning in the differential diagnosis of chronic recurrent respiratory tract infections?].
Wood preservatives as pentachlorophenol and lindane containing the highly toxic compound dioxin were common to be used to protect woods inside the house. In a case report a couple of symptoms are shown as upper airway irritation with dry mucosa, headaches, sleeplessness, lack of concentration and psychosomatic problems caused by those wood preservatives. The typical sequence of the symptoms is given. The results of blood and urine analysis on pentachlorophenol and lindane lead to investigations on indoor materials, air and dust. Taking out the contaminated materials is the best and only treatment.


A comparison of the stability of beverage cloud emulsions formulated with different gum acacia- and starch-based emulsifiers.
The performance of several hydrocolloids (3 gum acacias, 1 modified gum acacia, and 3 modified starches) in stabilizing beverage emulsions and corresponding model beverages was investigated employing different core materials, emulsifier usage levels, and storage temperatures. Concentrated emulsions were prepared using orange terpenes or Miglyol 812 (comprising medium-chain triglycerides, MCT) weighted 1:1 with ester gum, stored at 25 or 35 degrees C, and analyzed on days 0, 1, and 3. On day 3, model beverages were made from each emulsion, stored at both temperatures, and analyzed weekly for 4 wk. Stability of concentrated emulsions was assessed by measuring mean particle size and by visual observations of ringing; beverage stability was judged similarly and also by loss of turbidity. Particle size measurements showed concentrated emulsions containing gum acacia or modified gum acacia with either core material were stable over 3 d storage at both temperatures whereas those made with modified starches were not, destabilization being faster at 35 degrees C. Beverages based on orange terpenes, in contrast to Miglyol, yielded smaller mean particle sizes, both on manufacture and during storage, regardless of hydrocolloid used. Visual observations of ringing generally supported this finding. Modified gum acacia was evaluated at both recommended and higher usage levels, stability increasing in the latter case. In general, all gum acacia and modified gum acacia emulsifiers were superior in stability to those based on modified starches, at either temperature, for orange terpene-based beverages. In Miglyol-based beverages, similar results were seen, except 1 modified starch performed as well as the gum acacia products.


[Estimation of prosthodontic treatment results in dyscirculatory encephalopathy patients].
The interrelation between cerebral blood circulation and oral diseases as well as impact of prosthodontics treatment on cerebral hemodynamics was examined in the study. Cerebral hemodynamics was assessed by transcranial Doppler in 75 patients divided into three groups: (1) 30 patients with the initial form of vascular cerebral disorders (stage I-II); (2) 25 patients with severe vascular cerebral disorders (stage III); (3) 20 persons with no signs of encephalopathy as control group. Prosthodontic rehabilitation by full and partial teeth loss proved to contribute to normalization of indices of cerebral blood flow in patients with initial forms of cerebrovascular insufficiency (I and II stage of encephalopathy) and in patients with acute forms of insufficient brain blood supply (II and III stage of encephalopathy).


Effects of remifentanil on processing of auditory stimuli: a combined MEG/EEG study.
Remifentanil (Ultiva(®)) is a potent ultra-short acting mu-opioid receptor agonist used for perioperative pain treatment and anaesthesia. So far, it is not known how sensitive the cognitive processing of auditory perception elicited by the mismatch negativity (MMN) paradigm is to opioids. The present exploratory study investigated how the opioid remifentanil modulates different stages of auditory processing as reflected in the MMN(m) and P3a(m). We recorded electroencephalography (EEG) and magnetoencephalography (MEG) during auditory stimulation under remifentanil or placebo infusion in 20 healthy participants. For the MMN, a gender effect was found for tones deviating in frequency (± 10%) from the standard tone. Remifentanil increased the amplitude of the frequency MMN at F3 in females but not in males. No effect of treatment was found for the MMN(m) or the novel P3a(m). These results suggest that while the bottom-up stimulus change detection system for auditory stimuli appears to be relatively insensitive to opioids, the automatic attention switch caused by the change detection seems to be modulated by the opioid system in females. The multiple deviant paradigm including novel sounds is a promising tool for investigating pharmacological manipulation of different stages of auditory processing. Furthermore, combining the two techniques will yield more specific information about the drug effects on MMN(m).


Heart failure in women.
Increasingly high mortality from cardiovascular disease in women has sparked nationwide campaigns to raise awareness of this significant threat to women's health. Heart failure has the most lethal prognosis of the major cardiovascular diseases, yet women demonstrate an apparent survival advantage compared with men. Sex-linked disparities in heart failure risk factors and pathophysiology contribute to this divergent clinical outcome. Heart failure etiology and clinical manifestations unique to female sex exist. At age 40, the lifetime risk of developing heart failure is equal for men and women, whereas the lifetime risk of developing coronary heart disease is one in two for men and one in three for women. Understanding sex-inherent characteristics related to heart failure may help determine whether the optimal therapy for this prevalent syndrome should be modified according to sex. Until prospective trial data prove otherwise, heart failure treatment guidelines should be uniformly applied to both women and men.


Empowering the Physiotherapy Profession in Ethiopia through Leadership Development within the Doctoring Process.
Ethiopia recently introduced the Doctor of Physiotherapy (DPT) degree at Addis Ababa University as a mechanism to increase the work force capacity of primary care providers in the health sector. The DPT program was supported by an international academic partnership and was designed to empower physiotherapists as leaders to move the profession forward. The curriculum was framed by core pedagogical principles and strategies and was phased into two programs. First, the 4-year Advanced Standing DPT program focused on developing registered Ethiopian physiotherapists with Bachelor of Science degrees as academic faculty. Second, these new faculty would then sustain a 6-year Generic DPT program that would matriculate students upon graduation from high school. The curriculum represented depth and breadth of foundation and clinical sciences, evidence-based practice, clinical reasoning skills, and interprofessional education opportunities. A leadership thread provided opportunities to develop skills necessary to effectively navigate and manage the challenges faced by the profession. The main outcomes included (1) an 8-year international partnership, (2) the academic performance of students, and (3) and leadership capabilities as demonstrated through activities and assignments. While the program has been criticized as an unnecessary extravagance for Ethiopia, the advantages of the DPT degree were revealed in a direct comparison to other academic physiotherapy programs in Ethiopia. In the end, because the DPT is new to the country, it will take time to fully understand the true impact within the Ethiopian health system.


Combined Exosomal GPC1, CD82, and Serum CA19-9 as Multiplex Targets: A Specific, Sensitive, and Reproducible Detection Panel for the Diagnosis of Pancreatic Cancer.
Pancreatic cancer is a highly lethal malignancy with poor prognosis due to the lack of early symptoms and resultant late diagnosis. Thus, it is extremely urgent to establish a simple and effective method for the early diagnosis of pancreatic cancer. Although some studies have provided positive evidence for the use of exosomal surface protein glypican-1 (GPC1) as a biomarker for early screening, its clinical application is still controversial. Here, we systematically verified the role of exosomal GPC1 as a potential screening biomarker. First, bottleneck problems of a stable detection method and an identification standard were systematically studied, and a Python-based standardized data processing method was established to analyze exosomal GPC1 expression. Second, a detection panel consisting of exosomal GPC1, exosomal cluster of differentiation 82 (CD82), and serum carbohydrate antigen 19-9 (CA19-9) was employed for pancreatic cancer detection. This panel exhibited excellent diagnostic results (AUC = 0.942) and could effectively distinguish healthy people from patients with pancreatic cancer (P value threshold = 0.2282) and patients with pancreatitis from patients with pancreatic cancer (P value threshold = 0.5467). IMPLICATIONS: These results indicate that the combined detection of exosomal GPC1, exosomal CD82, and serum CA19-9 shows great promise as a standard method for pancreatic cancer detection and that this panel could be further applied for screening pancreatic cancer in Chinese populations.


Missing value imputation for epistatic MAPs.
Epistatic miniarray profiling (E-MAPs) is a high-throughput approach capable of quantifying aggravating or alleviating genetic interactions between gene pairs. The datasets resulting from E-MAP experiments typically take the form of a symmetric pairwise matrix of interaction scores. These datasets have a significant number of missing values - up to 35% - that can reduce the effectiveness of some data analysis techniques and prevent the use of others. An effective method for imputing interactions would therefore increase the types of possible analysis, as well as increase the potential to identify novel functional interactions between gene pairs. Several methods have been developed to handle missing values in microarray data, but it is unclear how applicable these methods are to E-MAP data because of their pairwise nature and the significantly larger number of missing values. Here we evaluate four alternative imputation strategies, three local (Nearest neighbor-based) and one global (PCA-based), that have been modified to work with symmetric pairwise data. We identify different categories for the missing data based on their underlying cause, and show that values from the largest category can be imputed effectively. We compare local and global imputation approaches across a variety of distinct E-MAP datasets, showing that both are competitive and preferable to filling in with zeros. In addition we show that these methods are effective in an E-MAP from a different species, suggesting that pairwise imputation techniques will be increasingly useful as analogous epistasis mapping techniques are developed in different species. We show that strongly alleviating interactions are significantly more difficult to predict than strongly aggravating interactions. Finally we show that imputed interactions, generated using nearest neighbor methods, are enriched for annotations in the same manner as measured interactions. Therefore our method potentially expands the number of mapped epistatic interactions. In addition we make implementations of our algorithms available for use by other researchers. We address the problem of missing value imputation for E-MAPs, and suggest the use of symmetric nearest neighbor based approaches as they offer consistently accurate imputations across multiple datasets in a tractable manner.


Incorporation of loudness measures in active noise control.
An attempt has been made to use a modified version of a standard active noise control algorithm in order to take into account the unique response of the human auditory system. It has been shown in the past that decreasing the sound pressure level at a location does not guarantee a similar decrease in the perceived loudness at that location. Typically, active noise control is based on minimizing the "error signal" from a mechanical device such as a microphone, whose response is nominally flat across the frequency response range of the human ear. However, if the response of the ear can be approximated by digitally filtering the error signal before it reaches the adaptive controller, one can, in effect, minimize the more subjective loudness level, as opposed to the sound pressure level. The work reported here entails simulating active noise control based upon minimizing perceived loudness for a collection of input noise signals. A comparison of the loudness of the resulting error signal is made to the loudness of that resulting from standard sound pressure level minimization. It has been found that the effectiveness of this technique is largely dependent upon the nature of the input noise signal. Furthermore, this technique is judged to be worth considering for use with applications of active noise control where the uncontrolled noise more prominently constitutes low range audio frequencies (approximately 30 Hz-100 Hz) than medium range audio frequencies (approximately 300 Hz-600 Hz).


Balanced phase-contrast steady-state free precession (PC-SSFP): a novel technique for velocity encoding by gradient inversion.
A technique for measuring velocity is presented that combines cine phase contrast (PC) MRI and balanced steady-state free precession (SSFP) imaging, and is thus termed PC-SSFP. Flow encoding was performed without the introduction of additional velocity encoding gradients in order to keep the repetition time (TR) as short as in typical SSFP imaging sequences. Sensitivity to through-plane velocities was instead established by inverting (i.e., negating) all gradients along the slice-select direction. Velocity sensitivity (VENC) could be adjusted by altering the first moments of the slice-select gradients. Disturbances of the SSFP steady state were avoided by acquiring different flow echoes in consecutively (i.e., sequentially) executed scans, each over several cardiac cycles, using separate steady-state preparation periods. A comparison of phantom measurements with those from established 2D-cine-PC MRI demonstrated excellent correlation between both modalities. In examinations of volunteers, PC-SSFP exhibited a higher intrinsic signal-to-noise ratio (SNR) and consequently low phase noise in measured velocities compared to conventional PC scans. An additional benefit of PC-SSFP is that it relies less on in-flow-dependent signal enhancement, and thus yields more uniform SNRs and better depictions of vessel geometry throughout the whole cardiac cycle in structures with slow and/or pulsatile flow.


The AhpC and AhpD antioxidant defense system of Mycobacterium tuberculosis.
The peroxiredoxin AhpC from Mycobacterium tuberculosis has been expressed, purified, and characterized. It differs from other well characterized AhpC proteins in that it has three rather than one or two cysteine residues. Mutagenesis studies show that all three cysteine residues are important for catalytic activity. Analysis of the M. tuberculosis genome identified a second protein, AhpD, which has no sequence identity with AhpC but is under the control of the same promoter. This protein has also been cloned, expressed, purified, and characterized. AhpD, which has only been identified in the genomes of mycobacteria and Streptomyces viridosporus, is shown here to also be an alkylhydroperoxidase. The endogenous electron donor for catalytic turnover of the two proteins is not known, but both can be turned over with AhpF from Salmonella typhimurium or, particularly in the case of AhpC, with dithiothreitol. AhpC and AhpD reduce alkylhydroperoxides more effectively than H(2)O(2) but do not appear to interact with each other. These two proteins appear to be critical elements of the antioxidant defense system of M. tuberculosis and may be suitable targets for the development of novel anti-tuberculosis strategies.


Passive surveillance of United Kingdom bats for lyssaviruses (2005-2015).
Passive surveillance for lyssaviruses in UK bats has been ongoing since 1987 and has identified 13 cases of EBLV-2 from a single species; Myotis daubentonii. No other lyssavirus species has been detected. Between 2005 and 2015, 10 656 bats were submitted, representing 18 species, creating a spatially and temporally uneven sample of British bat fauna. Uniquely, three UK cases originate from a roost at Stokesay Castle in Shropshire, England, where daily checks for grounded and dead bats are undertaken and bat carcasses have been submitted for testing since 2007. Twenty per cent of Daubenton's bats submitted from Stokesay Castle since surveillance began, have tested positive for EBLV-2. Phylogenetic analysis reveals geographical clustering of UK viruses. Isolates from Stokesay Castle are more closely related to one another than to viruses from other regions. Daubenton's bats from Stokesay Castle represent a unique opportunity to study a natural population that appears to maintain EBLV-2 infection and may represent endemic infection at this site. Although the risk to public health from EBLV-2 is low, consequences of infection are severe and effective communication on the need for prompt post-exposure prophylaxis for anyone that has been bitten by a bat is essential.


Ecological constraints associated with genome size across salamander lineages.
Salamanders have some of the largest, and most variable, genome sizes among the vertebrates. Larger genomes have been associated with larger cell sizes, lower metabolic rates, and longer embryonic and larval durations in many different taxonomic groups. These life-history traits are often important for dictating fitness under different environmental conditions, suggesting that a species' genome size may have the potential to constrain its ecological distribution. We test how genome size varies with the ephemerality of larval habitat across the salamanders, predicting that species with larger genomes will be constrained to more permanent habitats that permit slower development, while species with smaller genomes will be more broadly distributed across the gradient of habitat ephemerality. We found that salamanders with larger genomes are almost exclusively associated with permanent aquatic habitats. In addition, the evolutionary transition rate between permanent and ephemeral larval habitats is much higher in salamander lineages with smaller genome sizes. These patterns suggest that genome size may act as an evolutionary constraint on the ecological habitats of salamanders, restricting those species with large genomes and slower development to habitats with permanent sources of water.


The Regulation of Leptin, Leptin Receptor and Pro-opiomelanocortin Expression by N-3 PUFAs in Diet-Induced Obese Mice Is Not Related to the Methylation of Their Promoters.
The expression of leptin is increased in obesity and inhibited by n-3 polyunsaturated fatty acids (n-3 PUFAs), but the underlying molecular mechanisms have not been firmly established. In this study, we investigated the effects of dietary n-3 PUFAs on the methylation of CpG islands in the promoter regions of the leptin, leptin-R and POMC genes, as well as the effects of n-3 PUFA status in early life on the modification of the promoters of these three genes. Male C57 BL/6J mice were fed a high-fat diet with one of four different fat types: sunflower oil (n-3 PUFA deficient), soy oil, fish oil, or a mixture of soy and fish oil (soy:fish oil = 1:1). Two low-fat diets with sunflower oil or soy oil served as controls. Female mice were fed two breeding diets, sunflower oil or a mixture of soy and fish oil (soy:fish oil = 1:1), during pregnancy and lactation to breed new pups. Compared to mice fed the control diets, the expression of leptin in fat tissue and leptin-R and POMC in the hypothalamus was higher in the diet-induced obesity (DIO) mice, and the n-3 PUFAs in the diets reversed these elevated expression levels. The mean methylation levels of CpG sites in the promoter regions of the leptin and POMC genes showed no difference between the DIO and the control diet groups nor between the n-3 PUFA-containing and -deficient diet groups. For the CpG sites in the promoter regions of leptin-R, no methylation was found in any of the DIO or control groups. Feeding mice with the n-3 PUFA diet during pregnancy and lactation did not affect CpG methylation in the leptin or POMC promoters. Our findings indicate that promoter DNA methylation may not be related to the expression of leptin, leptin-R or its related hypothalamic satiety regulator POMC.


Exponential propagation of large circular DNA by reconstitution of a chromosome-replication cycle.
Propagation of genetic information is a fundamental property of living organisms. Escherichia coli has a 4.6 Mb circular chromosome with a replication origin, oriC. While the oriC replication has been reconstituted in vitro more than 30 years ago, continuous repetition of the replication cycle has not yet been achieved. Here, we reconstituted the entire replication cycle with 14 purified enzymes (25 polypeptides) that catalyze initiation at oriC, bidirectional fork progression, Okazaki-fragment maturation and decatenation of the replicated circular products. Because decatenation provides covalently closed supercoiled monomers that are competent for the next round of replication initiation, the replication cycle repeats autonomously and continuously in an isothermal condition. This replication-cycle reaction (RCR) propagates ∼10 kb circular DNA exponentially as intact covalently closed molecules, even from a single DNA molecule, with a doubling time of ∼8 min and extremely high fidelity. Very large DNA up to 0.2 Mb is successfully propagated within 3 h. We further demonstrate a cell-free cloning in which RCR selectively propagates circular molecules constructed by a multi-fragment assembly reaction. Our results define the minimum element necessary for the repetition of the chromosome-replication cycle, and also provide a powerful in vitro tool to generate large circular DNA molecules without relying on conventional biological cloning.


Exudative epidermitis in pigs caused by toxigenic Staphylococcus chromogenes.
Staphylococcus chromogenes is closely related to Staphylococcus hyicus, which is recognised as the causative agent of exudative epidermitis (EE) in pigs. S. chromogenes is part of the normal skin flora of pigs, cattle and poultry and has so far been considered non-pathogenic to pigs. A strain of S. chromogenes producing exfoliative toxin type B, ExhB, was identified by the use of a multiplex PCR specific for the exfoliative toxins from S. hyicus. The exfoliative toxin from S. chromogenes reacted in immunoblot analysis with polyclonal and monoclonal antibodies specific to ExhB from S. hyicus and had an apparent molecular weight of 30 kDa. Sequencing the gene encoding the exfoliative toxin from S. chromogenes revealed that the molecular weight of the toxin with the signal peptide and the mature toxin was 30,553 and 26,694 Da, respectively. Comparison of the exhB genes from S. chromogenes strain VA654 and S. hyicus strain 1289D-88 showed differences in seven base pairs of the DNA sequences and in two amino acid residues in the deduced amino acid sequences. Pigs were experimentally inoculated with S. chromogenes strain VA654. By clinical observations and histopathological evaluation of the skin alterations, all pigs revealed development of generalized exudative epidermitis. No toxin producing S. hyicus was isolated from the pigs and all ExhB-positive bacterial isolates were identified as S. chromogenes. This confirmed that the disease-causing agent was the inoculated S. chromogenes strain VA654. The results of this study show that S. chromogenes may cause exudative epidermitis in pigs.


Predictors of favorable growth patterns during the obesity epidemic among US school children.
To report the prevalence of favorable growth patterns, including healthy weight maintenance (HWM) and return to healthy weight (RHW) among US school-age children. A longitudinal analysis of childhood growth patterns from the Early Childhood Longitudinal Study-Kindergarten Cohort was completed (n = 9416). The primary outcome included describing the prevalence of HWM/RHW patterns using consecutive child growth data from kindergarten to fifth grades. Multivariate logistic regression was used to explore predictors of HWM/RHW. Incidence of RHW is calculated by grade level. Seventy percent (n = 6617) of children enter kindergarten at a healthy weight and approximately 70% maintained a healthy weight through fifth grade. Among overweight/obese kindergartners, only 17.1% outgrew their weight risk (RHW) by fifth grade. Fewer than 1 in 5 at-risk children outgrow their weight risk during school-age yet a majority of healthy weight children can maintain healthy weight during a critical growth period. Future work should explore additional socioecologic factors associated with favorable growth.


Performance of three-dimensional printed nasopharyngeal swabs for COVID-19 testing.
At the start of the COVID-19 pandemic, the US faced nationwide shortages of nasopharyngeal swabs due to both overwhelmed supply chains and an increase in demand. To address this shortfall, multiple 3D printed swabs were ultimately produced and sold for COVID-19 testing. In this work, we present a framework for mechanical and functional bench-testing of nasopharyngeal swabs using standard and widely available material testing equipment. Using this framework, we offer a comprehensive, quantitative comparison of the 3D printed swabs to benchmark their performance against traditional flocked swabs. The test protocols were designed to emulate the clinical use of the nasopharyngeal swabs and to evaluate potential failure modes. Overall, the 3D printed swabs performed comparably to, or outperformed, the traditional swabs in all mechanical tests. While traditional swabs outperformed some of the new 3D printed swabs in terms of sample uptake and retention, similar amounts of RNA were recovered from both 3D printed and traditional swabs.


Detection and Quantification of Extraterrestrial Platinum Group Element Alloy Micronuggets from Archean Impactite Deposits by Low-Voltage Scanning Electron Microscopy/Energy-Dispersive X-ray Spectrometry.
Rare, heterogeneously composed platinum group element alloy micronuggets (PGNs) occur in primitive meteorites, micrometeorites, and terrestrial impactite deposits. To gain insight into the nature of these phases, we developed a workflow for the characterization of PGNs using modern scanning electron microscopy (SEM) and energy-dispersive X-ray spectrometry at a low accelerating voltage of 6 kV. Automated feature analysis-a combination of morphological image analysis and elemental analysis with stage control-allowed us to detect PGNs down to 200 nm over a relatively large analysis area of 53 mm2 with a conventional silicon drift detector (SDD). Hyperspectral imaging with a high-sensitivity, annular SDD can be performed at low beam current (∼100 pA) which improves the SEM image resolution and minimizes hydrocarbon contamination. The severe overlapping peaks of the platinum group element L and M line families at 2-3 keV and the Fe and Ni L line families at <1 keV can be resolved by peak deconvolution. Quantitative elemental analysis can be performed at a spatial resolution of <80 nm; however, the results are affected by background subtraction errors for the Fe L line family. Furthermore, the inaccuracy of the matrix correction coefficients may influence standards-based quantification with pure element reference samples.


Association of p27 and Cyclin D1 Expression and Benefit from Adjuvant Trastuzumab Treatment in HER2-Positive Early Breast Cancer: A TransHERA Study.
Purpose: To assess the prognostic and predictive value of selected biomarkers involved in cell-cycle regulation or proliferation in patients with HER2-positive early breast cancer.Experimental Design: Protein expression of TOP2A, Ki67, cyclin D1, and p27 was immunohistochemically determined in tissue microarrays of surgical specimens from 862 patients randomized to trastuzumab (1 or 2 years; N = 561) and observation (N = 301) arms of the HERA trial. The primary analysis endpoint was disease-free survival (DFS). Biomarkers were examined as continuous or categorical variables (predefined cutoffs). Interaction terms between biomarkers and treatment were assessed in multivariate Cox models adjusted for variables of clinical interest.Results: A significant interaction was detected between p27 and treatment (adjusted P = 0.0049). Trastuzumab effect was significant in the p27-low subgroup (≤70% p27-positive tumor cells; N = 318). HR Comb Trast vs. Obs 0.44, 95% CI, 0.29-0.65 (P < 0.001). No trastuzumab effect was observed in the p27-high subgroup N = 435; HR Comb Trast vs. Obs 0.97, 95% CI, 0.66-1.44, P = 0.89), indicating that these patients derived little or no benefit from trastuzumab treatment. A prognostic effect of p27 on DFS was observed, with p27-high patients experiencing half the hazard of a DFS event compared with low ones (HR p27 High vs. Low 0.49, 95% CI, 0.32-0.75). TOP2A, Ki67, and cyclin D1, as categorical variables were not predictive, whereas cyclin D1 as continuous variable was predictive of trastuzumab benefit.Conclusions: In TransHERA, patients with HER2-positive early breast cancer with low p27 expression in their tumors benefited from trastuzumab treatment, whereas patients with high p27 expression did not. Clin Cancer Res; 24(13); 3079-86. ©2018 AACR.


Hybrid spheroids as a tool for prediction of radiosensitivity in tumor therapy.
Optimization in radiotherapy may be conceivably achieved by individualized treatment regimens. For this, the radiosensitivity of the tumor cells to be treated must be known. A method is presented to show that the effect of radiation on tumor cells in spheroids can be quantitatively evaluated without complicated cell determinations of spheroid composition. This evaluation is based on the dynamics of inactivation of the colony forming ability of whole spheroids composed chiefly of non-transformed diploid fibroblasts and a minority of HeLa "test" cells. Here, spheroids of identical composition, but of different sizes are inactivated proportional to their sizes, thus obviating the need for tedious single cell procedures. The use of spheroids of different sizes permits the deduction of dose-effect relationships, and the innate radiosensitivity of tumors cells. This is a novel method for measuring the radio and chemosensitivity of tumors in primary culture, i.e. cells directly isolated from tumors.


Changes in mesenteric lymph node T cell phenotype and B and T cell homing properties after murine AIDS infection.
We studied MLN (mesenteric lymph nodes) T cell phenotype and MLN T and B cells homing properties after murine AIDS (acquired immunodeficiency syndrome) infection. Our results showed an increase in the percentage of CD4+ cells expressing CD44, CD54 and LPAM-1. There was also a decrease in the proportion of CD8+ cells but an increase in the percentage of CD8+ CD54+ cells. An increased proportion of CD11b+ (Mac1) cells suggested the recruitment of macrophages. Murine AIDS MLN cells labeled with 125I-UDR migrated back to the MLN but did not preferentially migrate to the ILP (intestinal lamina propria). Simultaneous staining for BRDU and IgA confirmed the inability of murine AIDS MLN cells to home to the ILP. These data indicate that murine AIDS infection altered the mucosal immune system while modifying MLN T cell phenotype and MLN T and B cells migratory properties.


Differential susceptibility of Aedes aegypti to infection by the American and Southeast Asian genotypes of dengue type 2 virus.
Outbreaks of dengue hemorrhagic fever have coincided with the introduction of the Southeast (SE) Asian genotype of dengue type 2 virus in the Western Hemisphere. This introduced genotype appears to be rapidly displacing the indigenous, American genotype of dengue 2 virus throughout the region. These field observations raise the possibility that the SE Asian genotype of dengue 2 is better adapted for vector transmission than its American counterpart. To evaluate this hypothesis, we compared the ability of viral strains of the SE Asian and American genotypes to infect, replicate, and disseminate within vector mosquitoes (Aedes aegypti). Viral strains of the SE Asian genotype tended to infect and disseminate more efficiently in mosquitoes than did variants of the American genotype. These differences, however, were observed solely in field-derived mosquitoes, whereas viral infection rates were virtually identical in the laboratory-adapted Rockefeller colony of Ae. aegypti. Our findings could provide a physiological basis for the contrasting patterns of dengue virus genotype transmission and spread. Such an understanding of functional differences between viral strains and genotypes may ultimately improve surveillance and intervention strategies.


Predictors of treatment choice in lumbar spinal stenosis: a spine patient outcomes research trial study.
A retrospective cohort study. In this article, we examined the Spine Patient Outcomes Research Trial lumbar stenosis observational cohort to determine baseline patient characteristics that are predictive of the treatment patients chose. We also evaluated cutoff points on validated patient questionnaires that differentiate patients who chose surgery from those who chose nonsurgical management. Although the evidence from current studies suggests that surgical intervention is effective for lumbar spinal stenosis, the same studies show that nonoperative patients also improve. Thus, the reasons for patients choosing surgery versus nonoperative care are of continuing interest. Baseline patient and clinical characteristics between those who received operative intervention and those who received nonoperative care were compared to determine baseline predictors of lumbar spinal stenosis management. Also, an evaluation of responses to the 36-Item Short Form Health Survey Bodily Pain (BP), 36-Item Short Form Health Survey Physical Function (PF), and the modified Oswestry Disability Index (ODI) questionnaires was performed to determine the percentage of patients choosing surgical versus nonoperative care relative to their initial questionnaire values. This analysis looked at the 356 patients in the observational spinal stenosis cohort of Spine Patient Outcomes Research Trial who completed at least 1 follow-up visit. Patients choosing surgery were younger (P = 0.022), had worse BP (P < 0.001), worse PF (P < 0.001), worse ODI (P < 0.001), worse Stenosis Bothersomeness Index (P < 0.001), were dissatisfied with their symptoms (P = 0.001), and had a worse self-assessed health trend (P < 0.001). Patients tended to choose surgery if they had lateral recess stenosis (P = 0.022). Kaplan-Meier curves demonstrate that patients with a BP score of 32 or less, PF score of 30 or less, and ODI greater than 29 chose surgery 75% of the time. A greater understanding of baseline characteristics that influence patient choices in the treatment of lumbar spinal stenosis can aid the patient and the surgeon during the shared decision-making process.


Appearance of beta 1,4 N-acetylgalactosaminyltransferase (glycosphingolipids GA2/GM2/GD2 synthase) in embryonic chicken vitreous humor during development.
beta 1,4 N-Acetylgalactosaminyltransferase (GalNAcT) is a type II integral membrane protein of the Golgi apparatus that catalyzes the synthesis of the glycosphingolipids GM2, GD2, and GA2. The activity of GalNAcT in chick retinal cells increases 6-fold between embryonic days 7 and 14. Because GalNAcT, like many Golgi glycosyltransferases, is proteolytically cleaved from Golgi membranes to release a soluble form into the culture medium of cells transfected with the cloned human enzyme, we tested whether GalNAcT might be released from embryonic retinal cells into the vitreous humor. Samples of vitreous humor and plasma and extracts of retinal cells were assayed for GalNAcT activity. The activity of a soluble form of GalNAcT in embryonic chick vitreous humor was nearly undetectable until embryonic day 10, then increased more than six fold until day 16, and remained at that level until birth. The activity was identified as authentic GalNAcT based on a requirement for Mn++, GSL substrate specificity, and product characterization. GalNAcT activity in embryonic plasma was roughly 10% that of the corresponding vitreous humor, suggesting that the plasma was not the source of the activity in the vitreous. GalNAcT in embryonic chicken vitreous humor is likely due either to a specific release from neural retinal cells or due to non-specific lysis of these cells during apoptosis associated with the development of the retina. Regardless of the source, GalNAcT in the vitreous humor has the potential to function as a lectin by binding to gangliosides GD3 and GM3 on the surface of retinal cells and, thereby, to influence neuronal development.


In vitro comparison of inhibitors of inducible nitric oxide synthase in a macrophage model.
Nitric oxide (NO) has been shown to decrease cardiac performance, induce global hypotension, and generate oxygen free-radicals. Nitric oxide is produced from the conversion of L-arginine to L-citrulline by inducible nitric oxide synthase (iNOS) and is a component of many cellular second messenger systems. It is not clearly understood if NO and iNOS are compensatory mechanisms or pathological processes in heart failure, and this study was designed to understand better inhibition of iNOS in a cell culture model. Inhibitors of iNOS were compared for in vitro capability of inhibiting the production of NO. Ethanol and S-methylisothiourea (MITU) were applied to macrophage populations in 120 microM and 1 microM, 100 and 10 nM for an 8-h incubation. Level of iNOS expression was measured in the ethanol-treated populations using an anti-iNOS primary antibody with a fluorescent labeled secondary antibody. Serum nitrites were measured in both treatment groups by the nonenzymatic Griess method to determine enzyme function. Our data indicate that ethanol demonstrates a stimulation and simultaneous inhibition of iNOS during an 8-h incubation. No dose-dependent correlation between amount of serum nitrites produced and ethanol treatment was observed. However, MITU demonstrated a clear inhibition of iNOS at 120 microM with a serum nitrite value of 25.7002 +/- 0.0647, with control values of 24.3421 microM. Lower concentrations of MITU also demonstrated no correlation. Although both agents display inhibitory effects upon iNOS, MITU seems to have no apparent simultaneous stimulation and may hold more potential as a post-translational inhibitor of iNOS.


Features of intracranial aneurysms in infants and report of a case.
An 11-month-old girl presented with seizures, papilledema and a left hemiparesis. Radiographic examination revealed a saccular right middle cerebral-artery aneurysm. Clipping was performed 16 days after admission. At follow-up a year later there was no residual neurological deficit. Aneurysms occurring in infants are relatively large and more peripheral in location compared with adults, and frequently are accompanied by seizures. Infants' aneurysms also tend to occupy the anterior circulation distribution, and their peripheral location may make them more amenable to surgical intervention.


Tuberculosis Transmission in Households and Classrooms of Adolescent Cases Compared to the Community in China.
The aim of this paper is to evaluate the link between the history of exposure to tuberculosis (TB) in the household and diagnosed TB cases at school, and to compare the detection rate of active TB among household contacts and classroom contacts of adolescent TB cases with the rates among contacts of healthy controls. From November 2016 to December 2017, a prospective matched case-control study was conducted using passively identified index adolescent student cases from the TB surveillance system and healthy controls (matched by county, school type, sex, age and ethnicity). Contacts in households and classrooms of index cases and of controls were investigated. Matched tabulation of 117 case-control pairs revealed exposure to TB in the household as a strong risk factor (odds ratio (OR) = 21.0, 95% confidence interval (CI): 3.4, 868.6). Forty-five (case detection rate 0.69%) and two (case detection rate 0.03%) new active TB cases were detected among 6512 and 6480 classroom contacts of the index cases and controls, respectively. Having an index case in the classroom significantly increased the risk of classmates contracting active TB (OR = 22.5, 95% CI: 5.9, 191.4). Our findings suggested that previous exposure to TB in the household could lead a child to catch TB at school, then spread TB to classmates.


In vitro inhibitory effects of some heavy metals on human erythrocyte carbonic anhydrases.
The inhibition of two human carbonic anhydrase (HCA, EC 188.8.131.52) isozymes, the cytosolic HCA I and II, with heavy metal salts of Pb(II), Co(II) and Hg(II) has been investigated. Human erythrocyte CA-I isozyme was purified with a specific activity of 920 EUmg(-1) and a yield of 30% and CA-II isozyme was purified with a specific activity of 8000 EUmg(-1) and a yield of 40% using Sepharose-4B-L tyrosine-sulfanilamide affinity gel chromatography. The overall purification was approximately 104-fold for HCA-I and 900-fold for HCA-II. The inhibitory effects of different heavy metals (lead, cobalt and mercury) on CA activity were determined at low concentrations using the esterase method under in vitro conditions. Ki values for these metals were calculated from Lineweaver-Burk graphs as 1.0, 3.22 and 1.45 mM for HCA-I and 0.059, 1.382 and 0.32 mM for HCA-II respectively. Lead was a noncompetitive inhibitor for HCA-I and competitive for HCA-II, cobalt was competitive for HCA-I and noncompetitive for HCA-II and mercury was uncompetitive for both HCA-I and HCA-II. Lead was the best inhibitor for both HCA-I and HCA-II.


The Evolution of Physician Practice Styles: Evidence from Cardiologist Migration.
Physician treatment choices for observably similar patients vary dramatically across regions. This paper exploits cardiologist migration to disentangle the role of physician-specific factors such as preferences and learned behavior versus environment-level factors such as hospital capacity and productivity spillovers on physician behavior. Physicians starting in the same region and subsequently moving to dissimilar regions practice similarly before the move. After the move, physician behavior in the first year changes by 0.6-0.8 percentage points for each percentage point change in practice environment, with no further changes over time. This suggests environment factors explain between 60-80 percent of regional disparities in physician behavior.


Food supplements: survey of the ASL TO3.
In recent years, the increase of the consumption of supplements reveals problems concerning the safety of use. Current legislation states that supplements must be free of any therapeutic purpose and must have quality guarantees for the users' safety. The operators of the of Hygiene, Food and Nutrition Service (SIAN) of ASL TO 3 (province of Turin) conducted a surveillance in order to asses the situation on the territory, to know the use and consumption in local gyms. During the official control at the manufacturers / packers of supplements, located on the territory of the ASL TO 3, labels of supplement produced / packed were acquired, to analyze the components indicated, to carry out a deep evaluation of the individual product . Updating of the register of companies located in the territory of the ASL TO 3 was carried out; and during the period October 2011-March 2013 the labels of the products of these companies have been found and analyzed. The detailed content of the labels (ingredients, dose, method of recruitment, composition, etc. ..) was written in a database. It was also checked how many local gyms marketed supplements, and, in a small sample, a questionnaire was administered to visitors, in order to assess consumption. 355 labels were acquired and loaded on the database. 80% of them falls within the category of supplements based on ingredients derived from plants or similar. For these products was evaluated the presence on the label of not allowed plant extracts (according to the Ministerial Decree of 9 July 2012): only 2 products (of the same company) contained an ingredient not allowed. In all the examined labels was evaluated the presence of the substances for which there are specific warnings: 97% of the label is compliant and 3% are not in compliance. In the analyzed products the indications for use mainly found on the labels are related to increased demand and/or reduced intake, followed by antioxidant action. The study also evaluated the sale of supplements at gyms located on the territory of ASLTO3: 59 gyms are available on territory, but only in one of them supplements are sold. Some customers of these gyms have filled a questionnaire concerning the consumption of supplements. The processing of the questionnaires showed that 27% of respondents in the past 2 years used only occasionally food supplements. For 42% of the subjects the use of these products was to achieve weight loss, for 33% for athletes and 17% have used specific products in the case of particular physiological situations such as pregnancy and lactation. The reasons that lead to the use of dietary supplements, in all cases, are attributed to the improvement of health status. In addition, in 50% of cases the pharmacist has led to the use of these products or, alternatively, friends and relatives. The general practitioner is often not informed even in case of disturbances introduced after their use (seen in 8% of our sample). The majority of the sample (58%) said that they had benefited from the use of supplements and they are aware (68%) that there could be contraindications. A greater knowledge of the topic, with attention focused on the entire supply chain of the product, is essential to ensure the safety of consumers in the use of food supplements. For these reasons a more detailed check on the procedure is essential: selection and verification of suppliers (especially for raw materials coming from Eastern countries, because they are not subjected to a thorough inspection); traceability of products marketed; correspondence between manufactured and authorized products. Finally, promote an awareness campaign at all levels is necessary, including general practitioners for a conscious purchase.


Resting State EEG in Exercise Intervention Studies: A Systematic Review of Effects and Methods.
Background: Exercise has been shown to alter brain plasticity and is explored as a therapeutic intervention in a wide variety of neurological diseases. Electroencephalography (EEG) offers an inexpensive method of studying brain electrocortical activity shortly after exercise and thus offers a way of exploring the influence of exercise on the brain. We conducted a systematic review to summarize the current body of evidence regarding methods of EEG analysis and the reported effects of exercise interventions on EEG. Methods: PubMed, Web of Science and EMBASE were searched for studies investigating resting state EEG in exercise intervention studies carried out in participants >17 years of age and with no history of epilepsy. Further, studies solely investigating event-related potentials as an outcome measure were excluded. Relevant data were extracted, and a risk-of-bias assessment was carried out using the Cochrane risk-of-bias tool. A qualitative synthesis of results was carried out. A protocol for the systematic review was uploaded to https://www.crd.york.ac.uk/PROSPERO/ (ID: CRD42019134570) and the Preferred Reporting Items for Systematic Reviews (PRISMA) statement was followed. Results: Out of 1,993 records screened, 54 studies were included in a final qualitative synthesis with a total of 1,445 participants. Our synthesis showed that studies were mainly carried out using frequency analysis as an analytical method. Generally, findings across studies were inconsistent and few were adjusted for multiple comparisons. Studies were mainly of low quality and usually carried out in small populations, lowering the significance of results reported. Conclusions: Changes in the EEG as a result of an exercise intervention are elusive and difficult to replicate. Future studies should provide biologically sound hypotheses underlying assumptions, include larger populations and use standardized EEG methods to increase replicability. EEG remains an interesting methodology to examine the effects of exercise on the brain.


Upstream open reading frames of the barley Mla13 powdery mildew resistance gene function co-operatively to down-regulate translation.
SUMMARY To protect themselves against pathogen infection, plants have evolved multifarious defence mechanisms that include the production of antimicrobial compounds and hypersensitive cell death. This defence includes the regulation of expression of resistance proteins, which function to detect pathogen effectors and control the response. Barley Mla is one of several Ml genes that confer specific resistance to the powdery mildew fungus, Blumeria graminis f. sp. hordei. The Mla13 allele contains a long (523 nt) transcript leader region with three upstream open reading frames (uORFs) and two alternatively spliced introns. The lengths of the Mla13 uORFs, which encode up to 70 amino acid peptides, are directly influenced by the splicing of these introns. We have used in vivo and in vitro translation assays to show that Mla13 uORFs function co-operatively to down-regulate translation of the parent cistron up to 13-fold. However, resistance conferred by constitutively transcribed Mla appears to be unaffected by removal of these uORFs, signifying that a potential increase in MLA13 protein is innocuous to barley cells. In addition, cells that possess a predicted increase in MLA13 translation via over-expression and uORF mutation retain their requirement for RAR1, suggesting that this increase is not sufficient to overcome the concentration threshold required for activation of RAR1-independent resistance.


Intra-articular lidocaine versus intravenous sedation for the reduction of anterior shoulder dislocations in the emergency department.
The objective was to compare intra-articular lidocaine (IAL) versus intravenous sedation (IVS) for the reduction of acute, anterior shoulder dislocations in the emergency department (ED) in terms of ED length of stay, rate of successful reductions, patient satisfaction, and complications. This was a prospective, randomized trial. Patients in the IAL group received 4 mg/kg (up to 200 mg) of 1% lidocaine injected into the glenohumeral joint using a lateral approach. Patients in the IVS group received medications for sedation as per the discretion of the treating physician. Follow-up was arranged within 2 weeks of the ED visit to assess for complications. Forty-four patients (25 IAL, 19 IVS) were included. This trial was stopped early owing to a combination of unexpected findings in success, resource limitations, and difficulty in patient enrolment. Median time from first physician assessment to patient discharge was not different between the IAL (170 minutes) group and the IVS (145 minutes) group (Δ -25 minutes; 95% CI -32, 70; p = 0.46). There was a significantly lower rate (p < 0.001) of successful closed reduction in the IAL group (48%) compared to the IVS group (100%). Patient satisfaction and physician ease of reduction were higher in the IVS group compared to the IAL group (p < 0.05). There were no reported complications in either group at time of reduction or follow-up. There was no difference in ED length of stay between groups. There was a lower rate of successful reductions and lower satisfaction scores in the IAL group.