Oxygen-17 appears only in protein in water-stressed soybean leaves labeled by (17)O2.
We have used a rotational-echo adiabatic-passage double-resonance (13)C{(17)O} solid-state NMR experiment to prove that the glycine produced in the oxygenase reaction of ribulose bisphosphate carboxylase-oxygenase is incorporated exclusively into protein (or protein precursors) of intact, water-stressed soybean leaves exposed to (13)CO(2) and (17)O(2). The water stress increased stomatal resistance and decreased gas exchange so that the Calvin cycle in the leaf chloroplasts was no more than 35% (13)C isotopically enriched. Labeled O(2) levels were sufficient, however, to increase the (17)O isotopic concentration of oxygenase products 20-fold over the natural-abundance level of 0.04%. The observed direct incorporation of glycine into protein shows that water stress suppresses photorespiration in soybean leaves.


Recent progress in the synthesis of inorganic nanoparticles.
Nanoparticles probably constitute the largest class of nanomaterials. Nanoparticles of several inorganic materials have been prepared by employing a variety of synthetic strategies. Besides synthesizing nanoparticles, there has been considerable effort to selectively prepare nanoparticles of different shapes. In view of the great interest in inorganic nanoparticles evinced in the last few years, we have prepared this perspective on the present status of the synthesis of inorganic nanoparticles. This article includes a brief discussion of methods followed by reports on the synthesis of nanoparticles of various classes of inorganic materials such as metals, alloys, oxides chalcogenides and pnictides. A brief section on core-shell nanoparticles is also included.


Size-specific fecundity and the influence of lifetime size variation upon effective population size in Abies balsamea.
The hierarchy of plant size often present in dense populations of plants and the close correlation found between size and fecundity can result in an unequal distribution of fecundity, which reduces the ratio of effective population size/census number (Ne/N). Such an effect has been found previously in annuals, but no study has hitherto tested for the effect in the lifetime fecundity variation of a perennial population. We use the demographically stable size distribution to be found in natural, wave-regenerating populations of balsam fir, Abies balsamea, in order to estimate Ne/N. In both wave-regenerating and normal forests our estimated values of Ne/N were about twice those previously reported for annuals. We suggest that fecundity variance is expected to be smaller in trees and other long-lived perennials than in annuals because density-dependent mortality operates more strongly in the prereproductive phase of long-lived plants.


Norwegian Soils and Waters Contain Mesophilic, Plastic-Degrading Bacteria.
Plastic pollution has become one of the most critical environmental issues, as rapidly increasing production, compounded by persistence of plastic wastes in the environment, are outpacing efforts to keep ecosystems plastic-free. A switch to plastics more amenable to microbial attack is one of several possible responses. Against this background, the current study describes the isolation, enumeration and polyphasic characterization of plastic-degrading bacteria present in Norwegian terrestrial and aquatic habits. It shows that these bacteria are present in relatively high numbers, and that plastic-degrading capabilities are found in several taxa, most especially Streptomyces. Some isolates wereable to degrade several plastics. Notably, a Rhodococcus sp. and a Streptomyces sp. degraded, respectively, four and six of the eight plastics investigated and a number of other polymers relevant for plastic blends. The paper also has a methodological aspect, presenting various approaches for assaying plastic-degrading properties and a PCR/sequencing-based approach for the identification of potential polyethylene terephthalate-degrading genes. A candidate gene was detected in several Streptomyces isolates. The study shows that Norwegian environments are a rich source of bacteria with the ability to degrade bioplastics possibly representing a natural remediation capacity, as well as a potential source of useful enzymes.


Acalabrutinib with or without obinutuzumab versus chlorambucil and obinutuzmab for treatment-naive chronic lymphocytic leukaemia (ELEVATE TN): a randomised, controlled, phase 3 trial.
Acalabrutinib is a selective, covalent Bruton tyrosine-kinase inhibitor with activity in chronic lymphocytic leukaemia. We compare the efficacy of acalabrutinib with or without obinutuzumab against chlorambucil with obinutuzumab in patients with treatment-naive chronic lymphocytic leukaemia. ELEVATE TN is a global, phase 3, multicentre, open-label study in patients with treatment-naive chronic lymphocytic leukaemia done at 142 academic and community hospitals in 18 countries. Eligible patients had untreated chronic lymphocytic leukaemia and were aged 65 years or older, or older than 18 years and younger than 65 years with creatinine clearance of 30-69 mL/min (calculated by use of the Cockcroft-Gault equation) or Cumulative Illness Rating Scale for Geriatrics score greater than 6. Additional criteria included an Eastern Cooperative Oncology Group performance status score of 2 or less and adequate haematologic, hepatic, and renal function. Patients with significant cardiovascular disease were excluded, and concomitant treatment with warfarin or equivalent vitamin K antagonists was prohibited. Patients were randomly assigned (1:1:1) centrally via an interactive voice or web response system to receive acalabrutinib and obinutuzumab, acalabrutinib monotherapy, or obinutuzumab and oral chlorambucil. Treatments were administered in 28-day cycles. To reduce infusion-related reactions, acalabrutinib was administered for one cycle before obinutuzumab administration. Oral acalabrutinib was administered (100 mg) twice a day until progressive disease or unacceptable toxic effects occurred. In the acalabrutinib-obinutuzumab group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 2 and on day 1 (1000 mg) of cycles 3-7. In the obinutuzumab-chlorambucil group, intravenous obinutuzumab was given on days 1 (100 mg), 2 (900 mg), 8 (1000 mg), and 15 (1000 mg) of cycle 1 and on day 1 (1000 mg) of cycles 2-6. Oral chlorambucil was given (0·5 mg/kg) on days 1 and 15 of each cycle, for six cycles. The primary endpoint was progression-free survival between the two combination-therapy groups, assessed by independent review committee. Crossover to acalabrutinib was allowed in patients who progressed on obinutuzumab-chlorambucil. Safety was assessed in all patients who received at least one dose of treatment. Enrolment for this trial is complete, and the study is registered at ClinicalTrials.gov, NCT02475681. Between Sept 14, 2015, and Feb 8, 2017, we recruited 675 patients for assessment. 140 patients did not meet eligibility criteria, and 535 patients were randomly assigned to treatment. 179 patients were assigned to receive acalabrutinib-obinutuzumab, 179 patients were assigned to receive acalabrutinib monotherapy, and 177 patients were assigned to receive obinutuzumab-chlorambucil. At median follow-up of 28·3 months (IQR 25·6-33·1), median progression-free survival was longer with acalabrutinib-obinutuzumab and acalabrutinib monotherapy, compared with obinutuzumab-chlorambucil (median not reached with acalabrutinib and obinutuzumab vs 22·6 months with obinutuzumab, hazard ratio [HR] 0·1; 95% CI 0·06-0·17, p<0·0001; and not reached with acalabrutinib monotherapy vs 22·6 months with obinutuzumab, 0·20; 0·13-0·3, p<0·0001). Estimated progression-free survival at 24 months was 93% with acalabrutinib-obinutuzumab (95% CI 87-96%), 87% with acalabrutinib monotherapy (81-92%), and 47% with obinutuzumab-chlorambucil (39-55%). The most common grade 3 or higher adverse event across groups was neutropenia (53 [30%] of 178 patients in the acalabrutinib-obinutuzumab group, 17 [9%] of 179 patients in the acalabrutinib group, and 70 [41%] of 169 patients in the obinutuzumab-chlorambucil group). All-grade infusion reactions were less frequent with acalabrutinib-obinutuzumab (24 [13%] of 178 patients) than obinutuzumab-chlorambucil (67 [40%] of 169 patients). Grade 3 or higher infections occurred in 37 (21%) patients given acalabrutinib-obinutuzumab, 25 (14%) patients given acalabrutinib monotherapy, and 14 (8%) patients given obinutuzumab-chlorambucil. Deaths occurred in eight (4%) patients given acalabrutinib-obinutuzumab, 12 (7%) patients given acalabrutinib, and 15 (9%) patients given obinutuzumab-chlorambucil. Acalabrutinib with or without obinutuzumab significantly improved progression-free survival over obinutuzumab-chlorambucil chemoimmunotherapy, providing a chemotherapy-free treatment option with an acceptable side-effect profile that was consistent with previous studies. These data support the use of acalabrutinib in combination with obinutuzumab or alone as a new treatment option for patients with treatment-naive symptomatic chronic lymphocytic leukaemia. Acerta Pharma, a member of the AstraZeneca Group, and R35 CA198183 (to JCB).


Linitis plastica of the rectum secondary to bladder carcinoma: a report of two cases and its MR features.
Rectal linitis plastica (RLP) is a circumferentially infiltrating intramural anaplastic carcinoma that results in a rigid constricted rectum with thickened walls. A long delay between the onset of symptoms and the diagnosis often occurs because RLP can mimic a lot of diseases and endoscopy and biopsies are often negative, owing to the fact that the mucosa is frequently unaffected in RLP. RLP secondary to bladder cancer is rarely described in the English literature. We present the first report of the MR features of secondary rectal linitis plastica from a bladder carcinoma. Two patients presented with changed bowel habits. All diagnostic tests were inconclusive. In both patients, pelvic T(2) weighted MR images revealed a double-layered thickening of the rectal wall with an inner isointense circumferential thickening of the submucosa and outer hypointense circumferential thickening of the muscular rectal wall. Based on MRI, further investigations were performed and secondary RLP was diagnosed. It is important to establish the diagnosis of RLP early because of its bad prognosis. The value of MRI in supporting the diagnosis of RLP should not be underestimated. As endoscopy plus biopsy can often be negative, we suggest that, if pelvic MRI shows a concentric double layered thickening of the rectal wall over a long segment, then the diagnosis of RLP should be considered. This should prompt further investigations either to confirm or rule out the diagnosis of RLP by performing endoscopy with deep rectal wall biopsies.


The neural correlates of volitional attention: A combined fMRI and ERP study.
Studies of visual-spatial attention typically use instructional cues to direct attention to a relevant location, but in everyday vision, attention is often focused volitionally, in the absence of external signals. Although investigations of cued attention comprise hundreds of behavioral and physiological studies, remarkably few studies of voluntary attention have addressed the challenging question of how spatial attention is initiated and controlled in the absence of external instructions, which we refer to as willed attention. To explore this question, we employed a trial-by-trial spatial attention task using electroencephalography and functional magnetic resonance imaging (fMRI). The fMRI results reveal a unique network of brain regions for willed attention that includes the anterior cingulate cortex, left middle frontal gyrus (MFG), and the left and right anterior insula (AI). We also observed two event-related potentials (ERPs) associated with willed attention; one with a frontal distribution occurring 250-350 ms postdecision cue onset (EWAC: Early Willed Attention Component), and another occurring between 400 and 800 ms postdecision-cue onset (WAC: Willed Attention Component). In addition, each ERP component uniquely correlated across subjects with different willed attention-specific sites of BOLD activation. The EWAC was correlated with the willed attention-specific left AI and left MFG activations and the later WAC was correlated only with left AI. These results offer a comprehensive and novel view of the electrophysiological and anatomical profile of willed attention and further illustrate the relationship between scalp-recorded ERPs and the BOLD response.


Crystal structure and functional characterization of an immunomodulatory salivary cystatin from the soft tick Ornithodoros moubata.
The saliva of blood-feeding parasites is a rich source of peptidase inhibitors that help to overcome the host's defence during host-parasite interactions. Using proteomic analysis, the cystatin OmC2 was demonstrated in the saliva of the soft tick Ornithodoros moubata, an important disease vector transmitting African swine fever virus and the spirochaete Borrelia duttoni. A structural, biochemical and biological characterization of this peptidase inhibitor was undertaken in the present study. Recombinant OmC2 was screened against a panel of physiologically relevant peptidases and was found to be an effective broad-specificity inhibitor of cysteine cathepsins, including endopeptidases (cathepsins L and S) and exopeptidases (cathepsins B, C and H). The crystal structure of OmC2 was determined at a resolution of 2.45 A (1 A=0.1 nm) and was used to describe the structure-inhibitory activity relationship. The biological impact of OmC2 was demonstrated both in vitro and in vivo. OmC2 affected the function of antigen-presenting mouse dendritic cells by reducing the production of the pro-inflammatory cytokines tumour necrosis factor alpha and interleukin-12, and proliferation of antigen-specific CD4+ T-cells. This suggests that OmC2 may suppress the host's adaptive immune response. Immunization of mice with OmC2 significantly suppressed the survival of O. moubata in infestation experiments. We conclude that OmC2 is a promising target for the development of a novel anti-tick vaccine to control O. moubata populations and combat the spread of associated diseases.


Predictors of treatment outcome in cognitive behavioral therapy for intermittent explosive disorder: A preliminary analysis.
The present study examined potential treatment outcome predictors of a multicomponent cognitive behavioral intervention for intermittent explosive disorder (IED). The sample (n = 64; 22 female) consisted of individuals with a current diagnosis of IED that completed treatment across three study trials. Treatment outcome predictors assessed included demographic variables, psychiatric comorbidity, symptom severity, and treatment motivation/engagement. Treatment outcomes were (a) change in number of past-week aggressive acts from pretreatment to posttreatment and (b) presence of IED diagnosis at posttreatment. Results indicated those who endorsed lower trait anger were more likely to remit from IED diagnosis at posttreatment. No other variables were found to significantly predict treatment outcome. These findings support the notion that cognitive behavioral therapy can be effective for a wide range of individuals with IED, with little variation in efficaciousness based on presence of demographic characteristics, comorbid disorders, or treatment motivation/engagement. This seems to be particularly the case for individuals with lower levels of trait anger. (PsycInfo Database Record (c) 2023 APA, all rights reserved).


Ozone and natural systems: understanding exposure, response, and risk.
Research aimed at understanding the response of plants to ozone has been conducted for over four decades but little of it has addressed intact natural systems. Even so, there is sufficient scientific information at this time to support air quality standards that will protect natural terrestrial ecosystems from ozone. What is unknown is the risk associated with continued exposure of natural systems, including both above- and below-ground components, in combination with other stresses including changing temperature and precipitation, elevated carbon dioxide, pests and pathogens, invasive species, and other activities that may fragment the landscape. Research to support an assessment of the ecological risk associated with ozone as it exists, in a milieu of stresses, must include endpoints beyond those addressed in the past, primarily productivity and species composition. To estimate the risk to society of ozone impacts on natural systems, endpoints such as the integrity of soil food webs, the quantity and quality of water supplied from terrestrial ecosystems, wildlife and recreational values, and the transfer and fate of carbon, nutrients, and water within the systems must be quantified. Not only will this research provide the basis for a sound estimate of risk, but also it will improve our understanding of fundamental ecosystem processes.


Bordetella bronchiseptica and Bordetella pertussis: Similarities and Differences in Infection, Immuno-Modulation, and Vaccine Considerations.
Bordetella pertussis and Bordetella bronchiseptica belong to the genus Bordetella, which comprises 14 other species. B. pertussis is responsible for whooping cough in humans, a severe infection in children and less severe or chronic in adults. These infections are restricted to humans and currently increasing worldwide. B. bronchiseptica is involved in diverse respiratory infections in a wide range of mammals. For instance, the canine infectious respiratory disease complex (CIRDC), characterized by a chronic cough in dogs. At the same time, it is increasingly implicated in human infections, while remaining an important pathogen in the veterinary field. Both Bordetella can evade and modulate host immune responses to support their persistence, although it is more pronounced in B. bronchiseptica infection. The protective immune responses elicited by both pathogens are comparable, while there are important characteristics in the mechanisms that differ. However, B. pertussis pathogenesis is more difficult to decipher in animal models than those of B. bronchiseptica because of its restriction to humans. Nevertheless, the licensed vaccines for each Bordetella are different in terms of formulation, route of administration and immune responses induced, with no known cross-reaction between them. Moreover, the target of the mucosal tissues and the induction of long-lasting cellular and humoral responses are required to control and eliminate Bordetella. In addition, the interaction between both veterinary and human fields are essential for the control of this genus, by preventing the infections in animals and the subsequent zoonotic transmission to humans.


F:\DOCS\DOCS--physicians and automation.
While a paperless system may not be commonplace today, strides are being taken by groups such as CPRI to ensure the development of such a system. Several hospitals and clinics are moving toward or have implemented paperless or limited paper environments using patient-centered systems where charting is performed at the "bedside" of the patient through sophisticated software and hardware systems. Such systems will continue to evolve until the ATM of patient care is created. At that time, patients' access to their own information will be an acceptable phenomenon, physician use of computers will be commonplace, acceptance that adjunct knowledge bases must be coupled with the human skills of the physician, and test redundancy will be considered intolerable. These steps will contribute to the cost reductions needed to truly "reform" health care and create a value-added product for the United States.


Intracellular antibody-mediated immunity and the role of TRIM21.
Protection against bacterial and viral pathogens by antibodies has always been thought to end at the cell surface. Once inside the cell, a pathogen was understood to be safe from humoral immunity. However, it has now been found that antibodies can routinely enter cells attached to viral particles and mediate an intracellular immune response. Antibody-coated virions are detected inside the cell by means of an intracellular antibody receptor, TRIM21, which directs their degradation by recruitment of the ubiquitin-proteasome system. In this article we assess how this discovery alters our view of the way in which antibodies neutralise viral infection. We also consider the antiviral function of TRIM21 in the context of its other reported roles in immune signalling and autoimmunity. Finally, we discuss the conceptual implications of intracellular antibody immunity and how it alters our view of the discrete separation of extracellular and intracellular environments.


[Interaction of NADH-dehydrogenase from M. lysodeikticus membranes with lipids in a reconstituted system].
The NADH-dehydrogenase isolated from the M. lysodeikticus membranes was reconstituted into liposomes from the lipids obtained from the same membranes. The presence and degree of the reconstitution were investigated by two-dimensional immunoelectrophoresis and photoreactive hydrophobic label. The quenching of protein fluorescence by the aqueous quencher J- was practically the same for the enzyme in the reconstituted system and in the detergent solution, whereas the quencher interacting with the membrane--cetylpyridinium chloride--was effective in the first case and not effective in the second one. Evidence for the energy transfer from protein chromophores of NADH dehydrogenase in the proteoliposomes (lambda excit = 286 nm) to the hydrophobic fluorescent probe pyrene was obtained. It was found that about 30% of the chromophores in the enzyme molecule are involved in this process. The hydrophobic spin probe, whose paramagnetic fragment is located on the surface and not inside the hydrophobic phase of the membrane, can act as electron acceptor during NADH oxidation in the reconstituted system. The data obtained are suggestive of the exposure of the bulk of the enzyme molecule to the environment and of interaction of the smaller part of the molecule with the lipid phase. The active center is located on the part of the enzyme molecule which is exposed to water. It is assumed that the NADH-dehydrogenase molecule is exposed to water. It is assumed that the NADH-dehydrogenase molecule is involved in heat diffusion which facilitates the active center interaction with the membrane surface.


Mechanism of Electroacupuncture on Postoperative Ileus Induced by Surgical Stress in Rats.
Objectives: Acupuncture has been used for treating gastrointestinal (GI) disorders such as postoperative nausea and vomiting. Electroacupuncture (EA) accelerates GI transit following surgery and ameliorates postoperative ileus (POI) to restore colonic transit (CT); however, the mechanisms of this EA-induced restoration remain unclear. The aims of this study were to show CT following surgery and the effects of EA at ST 36 on POI induced by surgical stress (SS) in 45 conscious, male Sprague-Dawley rats. Materials and Methods: An operation was performed in each rat, setting a cannula into the cecum to connect the proximal colon to inject markers. On the day after surgery, 20 metal radiopaque markers were administered to the proximal colon of each rat. These markers were visible throughout the GI tract on soft X-ray immediately after administration and up to 240 minutes afterward. The rats were divided into 5 groups with 9 rats in each group: (1) SS; (2) 5 days post surgery (POST-5D); (3) SS + phentolamine; (4) EA alone; and (5) EA + atropine. The EA was performed at ST 36 for 20 minutes at a frequency of 10 Hz and agents were administered in the appropriate groups before markers were administered and measurements were taken. Measurements were performed the day after surgery except in the POST 5-D group. CT was calculated by the geometric center on the images showing the CT for each rat. Results: CT after surgery was delayed significantly and phentolamine accelerated CT. EA restored CT following surgery and atropine abolished the effect of EA on CT. Conclusions: The current study demonstrated that surgery induced a delay in CT through the sympathetic pathway via α-adrenoreceptors; CT was restored by EA. These results suggest that EA can be used to treat POI through mediation of the autonomic nervous system.


[Role of transvesical ultrasonic scanning in the diagnosis of causes of ureteral stenosis in patients with cervical cancer].
gamma-Beam therapy of combined radiation therapy are frequently followed by ureteral obstruction, caused by a cervical cancer recurrence or pelvic postradiation fibrosis. The knowledge of a cause is very important for a choice of therapeutic tactics of obstructive uropathy. The purpose was to define the potentialities of transvesical ultrasound scanning (TVUSS) in order to reveal causes of disturbed urodynamics of the urinary tracts after radiation therapy of cervical cancer. TVUSS was performed in 17 women with a confirmed diagnosis. It turned out that a cervical cancer recurrence could be differentiated from postradiation fibrosis by specific ultrasound signs. Another group of 44 patients was investigated using this method to find out causes of disturbed urodynamics of the upper urinary tracts: postradiation pelvic fibrosis was noted in 7 patients, a recurrence of cervical cancer--in 19, a recurrence of cervical cancer with the involvement of the urinary bladder--in 11, and bladder carcinoma--in 3, in 3 other cases the diagnosis was not established as a result of difficulties in interpreting sonograms.


Vertical distributions and source identification of the radionuclides 239Pu and 240Pu in the sediments of the Liao River estuary, China.
Activity concentration of plutonium (Pu) and its isotopic compositions are extensively used for measuring transport processes of Pu and identifying its source. We investigated the spatial distribution characteristics of 239+240Pu activity concentrations and 240Pu/239Pu atom ratio in several sediment cores collected from the Liao River coastal zone. Additionally, we calculated the 239+240Pu inventories and based on the 240Pu/239Pu atom ratio to trace Pu source. The activity concentrations of 239+240Pu in surface sediments of the Liao River estuary ranged between 0.103 ± 0.008 and 0.978 ± 0.035 mBq/g, with an average of 0.294 ± 0.024 mBq/g. The 240Pu/239Pu atom ratios, ranging from 0.173 ± 0.047 to 0.215 ± 0.061 (mean: 0.188 ± 0.049 (1σ)), were consistent with global fallout value, which indicates the global atmospheric fallout is the main source of Pu in sediment cores from the both sides of Liao River estuary. As for the tidal flat core LT-2, the mean 240Pu/239Pu atom ratio, slightly higher than that of the global fallout value, was 0.217 ± 0.050. Such pattern of Pu isotopic compositions indicated that Pu on the tidal flat in the Liao River estuary is sourced from a combination of global fallout and close-in fallout from the PPG by ocean currents transporting. And by using a two end-member mixing model, the results indicate the relative contribution of the PPG close-in fallout to core LT-2 is round 27% and 73% can be attributed to global fallout and river input. Therefore, these results clearly indicate that the direct global fallout is the main source of Pu in the Liao River estuary.


Herpes Simplex Virus, APOEɛ4, and Cognitive Decline in Old Age: Results from the Betula Cohort Study.
Herpes simplex virus (HSV) has been suggested to play a role in Alzheimer's disease (AD) development. The aim of the present study was to investigate the early AD-related symptom episodic memory decline in relation to HSV and carriage of allele 4 of the apolipoprotein E gene (APOEɛ4) in a large population-based cohort with a long follow-up time. The study included 3,413 persons, with longitudinal data available for 1,293 persons with a mean follow-up time of 11.6 years. The associations between HSV carriage, APOEɛ4 carriage, and episodic memory was investigated at baseline, as well as in longitudinal analyses where individuals with and without HSV antibodies (HSV1/2 non-specific) were matched and episodic memory decline compared. Cross-sectional analyses revealed an age-dependent association of HSV carriage with lower episodic memory function, particularly among APOEɛ4 carriers (p = 0.008). Longitudinal analyses showed an increased risk of episodic memory decline in HSV carriers (≥65 years: p < 0.001, all ages: non-significant), and a significant interaction between HSV and APOEɛ4 for episodic memory decline (p < 0.001). In this large population-based cohort study, both cross-sectional and longitudinal results support an association between HSV carriage and declining episodic memory function, especially among APOEɛ4 carriers. The results strengthen the hypothesis that HSV is associated with AD development.


[Simple method of differential diagnosis of peripheral and central vertigo--development of diagnostic method and studies of 178 cases].
In patients who complain of vertigo or who have equilibrium disorders, it is often difficult to determine the etiology of the disorder, that is to determine whether it is dependent on a peripheral or central vestibular disorder. To attempt to determine the etiology in these cases, we divised a new method, the caloric eye tracking pattern test (CETP-Test). Seventeen normal subjects and 161 patients were tested. The latter group included 33 with peripheral disorders such as Meniere's disease, benign paroxysmal positional nystagmus, and others, and 128 with central disorders such as vertebral basilar artery insufficiency, cervical vertigo, and others, were tested. The cases of central disorders were limited to those patients whose eye tracking pattern before the caloric stimulation was normal. In normal subjects and in patients with peripheral disorders, it is well known that caloric nystagmus has little influence on the eye tracking pattern. In contrast, in patients with central vestibular disorders, caloric nystagmus evokes abnormalities on the eye tracking pattern, either superimposed or saccades, despite the fact that the eye tracking pattern before the caloric stimulation is normal. First we administer the eye tracking stimulation test using a target which moves horizontally at 0.3 cycle per second. Next, we perform the caloric test on the right ear, using 20 c.c. of ice water for 10 seconds. During the evoked caloric nystagmus we administer the eye tracking test once again. The eye tracking pattern is recorded for 20 seconds beginning 50 seconds after the start of the ice water injection. The procedure repeated on the left ear. The results on each case are presented as three patterns of ENG-recording. We may stat that in normal subjects and in patients with peripheral vestibular disorders, visual suppression of caloric nystagmus remains functional. Caloric induced nystagmus does not affect the CETP. In patients with central vestibular disorders, visual suppression of caloric nystagmus does not function properly because of defects in the visual suppression mechanism. Therefore, caloric nystagmus greatly influences the CETP. Consequently, the CETP may not be smooth when CETP test is administered to patients with central vestibular disorders. We may say also that the visual suppression to the vestibular nystagmus is evoked more strongly by pursuing a moving visual stimulus than by gazing a stational target. These results allow for a differential diagnosis between peripheral and central disorders.


Nutritional and Non-Nutritional Strategies in Bodybuilding: Impact on Kidney Function.
Bodybuilders routinely engage in many dietary and other practices purported to be harmful to kidney health. The development of acute kidney injury, focal segmental glomerular sclerosis (FSGS) and nephrocalcinosis may be particular risks. There is little evidence that high-protein diets and moderate creatine supplementation pose risks to individuals with normal kidney function though long-term high protein intake in those with underlying impairment of kidney function is inadvisable. The links between anabolic androgenic steroid use and FSGS are stronger, and there are undoubted dangers of nephrocalcinosis in those taking high doses of vitamins A, D and E. Dehydrating practices, including diuretic misuse, and NSAID use also carry potential risks. It is difficult to predict the effects of multiple practices carried out in concert. Investigations into subclinical kidney damage associated with these practices have rarely been undertaken. Future research is warranted to identify the clinical and subclinical harm associated with individual practices and combinations to enable appropriate and timely advice.


Anti-Androgenic Activity of Nardostachys jatamansi DC and Tribulus terrestris L. and Their Beneficial Effects on Polycystic Ovary Syndrome-Induced Rat Models.
Polycystic ovary syndrome (PCOS) is a major hyperandrogenic disorder. Many drugs prescribed specifically to treat PCOS have side effects; however, previous studies suggest that natural therapeutics including botanicals may be less invasive and equally effective for the management of PCOS. In the present study, plants were screened for antiandrogenic activity using the RIKILT yeast Androgen bioAssay (RAA). Selected positive plants were subsequently tested for their efficacy against PCOS induced by estradiol valerate (EV) in rat models. RAA revealed the antiandrogenic property of Nardostachys jatamansi DC (NJ), Tribulus terrestris L. (TT), and Embelia tsjeriam-cottam DC (EJ), whereas Whithania somnifera Dunal (WS), Symplocos racemosa Roxb. (SR), and Helicteres isora L. (HI) exhibited androgenic properties. EJ also exhibited mild androgenic activity and therefore was excluded from further study. EV administration reduced the weight gain and disrupted cyclicity in all rats. NJ and TT extract treatment normalized estrous cyclicity and steroidal hormonal levels and regularized ovarian follicular growth. The in vitro antiandrogenic activity of plant extracts and their positive effects on different parameters of PCOS were proved in vivo.


Automated quantification of myocardial tissue characteristics from native T1 mapping using neural networks with uncertainty-based quality-control.
Tissue characterisation with cardiovascular magnetic resonance (CMR) parametric mapping has the potential to detect and quantify both focal and diffuse alterations in myocardial structure not assessable by late gadolinium enhancement. Native T1 mapping in particular has shown promise as a useful biomarker to support diagnostic, therapeutic and prognostic decision-making in ischaemic and non-ischaemic cardiomyopathies. Convolutional neural networks (CNNs) with Bayesian inference are a category of artificial neural networks which model the uncertainty of the network output. This study presents an automated framework for tissue characterisation from native shortened modified Look-Locker inversion recovery ShMOLLI T1 mapping at 1.5 T using a Probabilistic Hierarchical Segmentation (PHiSeg) network (PHCUMIS 119-127, 2019). In addition, we use the uncertainty information provided by the PHiSeg network in a novel automated quality control (QC) step to identify uncertain T1 values. The PHiSeg network and QC were validated against manual analysis on a cohort of the UK Biobank containing healthy subjects and chronic cardiomyopathy patients (N=100 for the PHiSeg network and N=700 for the QC). We used the proposed method to obtain reference T1 ranges for the left ventricular (LV) myocardium in healthy subjects as well as common clinical cardiac conditions. T1 values computed from automatic and manual segmentations were highly correlated (r=0.97). Bland-Altman analysis showed good agreement between the automated and manual measurements. The average Dice metric was 0.84 for the LV myocardium. The sensitivity of detection of erroneous outputs was 91%. Finally, T1 values were automatically derived from 11,882 CMR exams from the UK Biobank. For the healthy cohort, the mean (SD) corrected T1 values were 926.61 (45.26), 934.39 (43.25) and 927.56 (50.36) for global, interventricular septum and free-wall respectively. The proposed pipeline allows for automatic analysis of myocardial native T1 mapping and includes a QC process to detect potentially erroneous results. T1 reference values were presented for healthy subjects and common clinical cardiac conditions from the largest cohort to date using T1-mapping images.


Diabetes, bone and glucose-lowering agents: basic biology.
Skeletal fragility often accompanies diabetes and does not appear to correlate with low bone mass or trauma severity in individuals with diabetes. Instead (and in contrast to those with osteoporotic bone disease), bone remodelling and bone turnover are compromised in both type 1 and type 2 diabetes, contributing to defective bone material quality. This review is one of a pair discussing the relationship between diabetes, bone and glucose-lowering agents; an accompanying review is provided in this issue of Diabetologia by Ann Schwartz (DOI: 10.1007/s00125-017-4283-6 ). This review presents basic science evidence that, alongside other organs, bone is affected in diabetes via impairments in glucose metabolism, toxic effects of glucose oxidative derivatives (advance glycation end-products [AGEs]), and via impairments in bone microvascular function and muscle endocrine function. The cellular and molecular basis for the effects of diabetes on bone are discussed, as is the impact of diabetes on the stem cell niche and fracture healing. Furthermore, the safety of clinically approved glucose-lowering therapies and the possibility of developing a single therapy that would be beneficial for both insulin sensitisation and diabetes bone syndrome are outlined.


Transforming growth factor-Beta binds reversibly in vitro to guglielmi detachable coils.
We determined the propensity for and reversibility of transforming growth factor-beta(TGFbeta) binding to uncoated Guglielmi Detachable Coils (GDC) and to GDC coated with extracellular matrix (ECM) proteins. Three 1.0 centimetre samples each of uncoated GDC-18 and of GDC-18 coated with either poly-L-lysine, laminin, type I collagen, type IV collagen, fibronectin, or poly-L-lysine and laminin were prepared. These samples were immersed briefly in a solution containing I(125)-labelled TGFbeta at a concentration of 0.225 mug/ml with initial specific activity of 123.3 mCi/mg (DuPont-NEN, Billerica, MA), and were counted using a scintillation counter. Each sample was then placed in a vial containing saline, shaken for 60 seconds, and counted again. Selected samples were immersed for varying periods within the TGFbeta solution and counted before and after saline rinse. Samples were rinsed one week after initial rinsing and counted again. The amount of binding between coil types was compared using the Student t test. For all samples initial binding of TGFbeta was in the order of 60-120 pg/cm. For the pre-rinse data there were no statistically significant differences between the amount bound to any single coil coating type relative to other coatings. Compared to the initial accumulations, the amount remaining after rinsing ranged from 40% (poly-L-lysine) to 63% (poly-L-lysine with laminin), with a mean of 55% among the seven coil types. After rinsing there was more growth factor remaining on uncoated coils than on poly-L-lysine-coated coils (p=0.05), fibronectin-coated coils (p=0.01), and type IV collagen-coated coils (p=0.04). There was a trend toward greater residual growth factor on coils coated with poly-L-lysine and laminin compared to coils coated with poly-L-lysine alone (p=0.10). Delayed, second rinsing of the samples one week after initial testing demonstrated only minor incremental loss of TGFbeta from the coil surfaces. After five minutes of immersion, accumulation was approximately 200% greater than that noted with brief submersion, but immersions lasting over five minutes did not yield increasing levels of TGFbeta binding. TGFbeta binds to GDC coils. Binding is not improved with ECM protein-coated coils compared to uncoated coils. The absolute amount of TGFbeta bound to the coil will likely result in local concentrations of growth factor in the order of those required for biological activity in vivo.


Permission to pass: on the role of p53 as a gatekeeper for aneuploidy.
Aneuploidy-the karyotype state in which the number of chromosomes deviates from a multiple of the haploid chromosome set-is common in cancer, where it is thought to facilitate tumor initiation and progression. However, it is poorly tolerated in healthy cells: during development and tissue homeostasis, aneuploid cells are efficiently cleared from the population. It is still largely unknown how cancer cells become, and adapt to being, aneuploid. P53, the gatekeeper of the genome, has been proposed to guard against aneuploidy. Aneuploidy in cancer genomes strongly correlates with mutations in TP53, and p53 is thought to prevent the propagation of aneuploid cells. Whether p53 also participates in preventing the mistakes in cell division that lead to aneuploidy is still under debate. In this review, we summarize the current understanding of the role of p53 in protecting cells from aneuploidy, and we explore the consequences of functional p53 loss for the propagation of aneuploidy in cancer.


Brain-orientated intensive care treatment in severe neonatal asphyxia. Effects of phenobarbitone protection.
The effect of applying brain-orientated neonatal intensive care for term infants with severe neonatal asphyxia was studied. Such treatment included protective phenobarbitone administration together with assisted ventilation and other measures to counteract postasphyxial cerebral oedema and any abrupt changes in blood pressure and oxygenation. The mortality rate and incidence of long-term sequelae were reduced appreciably, resulting in a 0-1 year mortality rate of 14% (previously 50%) and an incidence of neurodevelopmental handicap at 18 months of 17% (previously 50%). It is important in the management of infants with severe asphyxia at birth to avoid blood pressure fluctuations and to control neuronal epileptic activity by the use of barbiturates and early ventilator treatment.


Trends in inflammatory bowel disease infections and vaccinations in the past four decades: A high-level text mining analysis of PubMed publications.
We aimed at assessing the published literature on different prophylactic screening and vaccination options in inflammatory bowel disease (IBD) patients between 1980 and 2020. Special attention was attributed to latest data assessing covid-19 vaccinations. We have queried PubMed for all available IBD-related entries published during 1980-2020. The following data were extracted for each entry: PubMed unique article ID (PMID), title, publishing journal, abstract text, keywords (if any), and authors' affiliations. Two gastrointestinal specialists decided by consensus on a list of terms to classify entries. The terms belonged to four treatment groups: opportunistic infections, prophylactic screening, prophylactic vaccinations/treatment, and routine vaccines. Annual trends of publications for the years 1980-2020 were plotted for different screening, vaccinations and infection types. Slopes of publication trends were calculated by fitting regression lines to the annual number of publications. Overall, 98,339 IBD entries were published between 1980 and 2020. Of those, 7773 entries belonged to the investigated groups. Entries concerning opportunistic infections showed the sharpest rise, with 19 entries and 1980 to 423 entries in 2020 (slope 11.3, p < .001). Entries concerning prophylactic screening rose from 10 entries in 1980 to 204 entries in 2020 (slope 5.4, p < .001). Both entries concerning prophylactic vaccinations/treatments and routine vaccines did not show a significant rise (slope 0.33 and slope 0.92, respectively). During the COVID 19 pandemic, a total of 44 publications were identified. Of them, 37 were relevant to vaccines and immune reaction. Nineteen publications (51%) were guidelines/recommendations, and 14 (38%) assessed immune reaction to vaccination, most of them (11, 61%) to mRNA vaccines. During the past two decades, along with a rapid increase in biologic therapy, publications regarding opportunistic infections and prophylactic screening increased in a steep slope compared to the two decades in the pre-biologic area. During the COVID-19 pandemic, most publications included vaccination recommendations and guidelines and only 38% included real-world data assessing reaction to vaccinations. More research is needed.


Earth's interior. Dehydration melting at the top of the lower mantle.
The high water storage capacity of minerals in Earth's mantle transition zone (410- to 660-kilometer depth) implies the possibility of a deep H2O reservoir, which could cause dehydration melting of vertically flowing mantle. We examined the effects of downwelling from the transition zone into the lower mantle with high-pressure laboratory experiments, numerical modeling, and seismic P-to-S conversions recorded by a dense seismic array in North America. In experiments, the transition of hydrous ringwoodite to perovskite and (Mg,Fe)O produces intergranular melt. Detections of abrupt decreases in seismic velocity where downwelling mantle is inferred are consistent with partial melt below 660 kilometers. These results suggest hydration of a large region of the transition zone and that dehydration melting may act to trap H2O in the transition zone.


Eosinophilic Granulomatosis With Polyangiitis Following COVID-19 Vaccination: A Case Report.
The current emergence of the coronavirus disease 2019 (COVID-19) pandemic and the possible side effects of COVID-19 mRNA vaccination remain worrisome. Few cases of vaccination-related side effects, such as vasculitis, have been reported. Eosinophilic granulomatosis with polyangiitis (EGPA), also known as Churg-Strauss syndrome, is a type of vasculitis characterized by the histological richness of eosinophils, asthma, polyneuropathy, sinusitis, and skin or lung involvement. Here, we report the first case of new onset EGPA following COVID-19 vaccination in Korea. A 71-year old woman developed a skin rash and presented with progressive weakness of the upper and lower extremities after the BNT162b2 vaccination (Pfizer-BioNTech). She was diagnosed with EGPA and her symptoms improved after systemic steroid and immunosuppressant therapy. Although it is very rare, clinicians should be aware that EGPA may occur after COVID-19 vaccination.


Financial assessment of results of intervention to correct a housing-system problem on a dairy farm.
To monitor effects that improvements in housing facilities would have on herd performance. Financial measures were calculated to estimate whether improvements resulted in an improved financial status for the farm. Prospective, observational study. 160-cow dairy herd. Farm visits were conducted from 1990 to 1994. Areas for improvement were identified, and changes were recommended. Herd production and farm financial records were analyzed before, during, and after adoption of recommended changes. After improving facilities, somatic cell count was somewhat constant, but tended to decrease during the last 16 months of the study. During the last 8 months of the study, incidence for clinical cases of mastitis decreased to 3.3% per month. Reproductive variables improved dramatically after implementing use of a bull for breeding. Subjective evaluation of cow comfort and lameness indicated apparent improvements in each area. However, milk production remained fairly constant from January 1991 through December 1994. Review of the arm's financial status revealed that costs of production increased from 1990 through 1993, but decreased in 1994. Slow financial response to improvements were attributed to a large decrease in milk price in 1991 and a poor crop harvest in 1993. Thus, although progress was made toward financial stability, approximately 55% of the farm's assets (determined on a market-basis value) were represented by debt. It is important to monitor financial status when managing complex health problems that involve several aspects of a farm's operation.


Does previous intra-articular steroid injection increase the risk of joint infection following total hip arthroplasty or total knee arthroplasty? A meta-analysis.
Joint infection might be one of the rare but serious complications following a total knee or hip arthroplasty (TKA, THA). A previous intra-articular steroid injection was considered as a risk factor. The purpose of present study was to access the effects of ipsilateral intra-articular steroid injection followed by TKA or THA on the incidence of infections later. Clinical studies reporting infection in THA or TKA after previous injection of intra-articular steroid were identified from the online database of PubMed, Embase, the Cochrane Library, and additional manual searches until July 2013. The pooled effects were measured by risk difference (RD), together with 95% confidence intervals (CIs). A total of 11 related studies met our inclusion criteria. The final meta-analysis investigated 6 clinical studies designed as retrospectively created cohort studies with control groups, involving 1474 participants reporting 14 deep infections and 72 superficial infections. Compared with the control group, there was no significantly increased rate of infection among the participant with steroid injection prior to THA or TKA, with corresponding RD (95% CIs) of 0.01 (-0.01, 0.02) for deep infection, 0.01 (-0.02, 0.03) for superficial infection, and 0.02 (-0.02, 0.07) for total infection. The data from 3 prospective studies without control groups and 2 case-control studies were consistent with the results of our meta-analysis. No increased risk of infection among patients who received steroid injections prior to the surgery was identified from the present evidence. A multicenter prospective study with more defined variables is needed further investigate this issue.


The influence of corticospinal activity on TMS-evoked activity and connectivity in healthy subjects: A TMS-EEG study.
Combined transcranial magnetic stimulation (TMS) and electroencephalography (EEG) can be used to analyze cortical reactivity and connectivity. However, the effects of corticospinal and peripheral muscle activity on TMS-evoked potentials (TEPs) are not well understood. The aim of this paper is to evaluate the relationship between cortico-spinal activity, in the form of peripheral motor-evoked potentials (MEPs), and the TEPs from motor areas, along with the connectivity among activated brain areas. TMS was applied to left and right motor cortex (M1), separately, at motor threshold while multi-channel EEG responses were recorded in 17 healthy human subjects. Cortical excitability and source imaging analysis were performed for all trials at each stimulation location, as well as comparing trials resulting in MEPs to those without. Connectivity analysis was also performed comparing trials resulting in MEPs to those without. Cortical excitability results significantly differed between the MEP and no-MEP conditions for left M1 TMS at 60 ms (CP1, CP3, C1) and for right M1 TMS at 54 ms (CP6, C6). Connectivity analysis revealed higher outflow and inflow between M1 and somatosensory cortex bi-directionally for trials with MEPs than those without for both left M1 TMS (at 60, 100, 164 ms) and right M1 TMS (at 54, 100, and 164 ms). Both TEP amplitudes and connectivity measures related to motor and somatosensory areas ipsilateral to the stimulation were shown to correspond with peripheral MEP amplitudes. This suggests that cortico-spinal activation, along with the resulting somatosensory feedback, affects the cortical activity and dynamics within motor areas reflected in the TEPs. The findings suggest that TMS-EEG, along with adaptive connectivity estimators, can be used to evaluate the cortical dynamics associated with sensorimotor integration and proprioceptive manipulation along with the influence of peripheral muscle feedback.


An ethnographic study of participant roles in school bullying.
An ethnographic study in a 10th grade remedial class was undertaken in order to discern patterns of school bullying. Twenty 10th graders were observed over the course of one academic year as they interacted with their peers and teachers. The observations helped us identify dispositional and situational factors which influenced participant roles. In-depth interviews of students involved in school bullying showed how participants interpreted and explained their classroom behaviors. The analysis of the data gathered allowed the identification of four main actor roles recognized in the existing literature on bullying-the pure victim, the pure bully, the provocative-victim, and the bystander-as well as the differentiation between aggressive bullies and the bully managers. Most roles fluctuated according to specific circumstances and often appeared to be moderated by the teacher's management style and contextual variables. Some pupils assumed different roles in different contexts, sometimes changing roles within or between episodes. Teacher personality and style also had an impact on the frequencies and types of aggression and victimization. The use of an ethnographic research paradigm is discussed as an important supplement to positivistic studies of school bullying.


Structural analysis of an innate immunostimulant from broccoli, Brassica oleracea var. italica.
Vegetables are eaten as part of a healthy diet throughout the world, and some are also applied topically as a traditional medicine. We evaluated the innate immunostimulating activities of hot water extracts of various vegetables using the silkworm muscle contraction assay system, and found that broccoli, Brassica oleracea var. italica, contains a strong innate immunostimulant. We purified the innate immunostimulant from broccoli, and characterized the chemical structure by chemical analyses and NMR spectroscopy. The innate immunostimulant comprised galacturonic acid, galactose, glucose, arabinose, and rhamnose, and had a pectic-like polysaccharide structure. To determine the structural motif involved in the innate immunostimulating activity, we modified the structure by chemical and enzymatic treatment, and found that the activity was attenuated by pectinase digestion. These findings suggest that a pectic-like polysaccharide purified from broccoli has innate immune-stimulating activity, for which the polygalacturonic acid structure is necessary.


Enhanced three-dimensional deconvolution microscopy using a measured depth-varying point-spread function.
We present a technique to systematically measure the change in the blurring function of an optical microscope with distance between the source and the coverglass (the depth) and demonstrate its utility in three-dimensional (3D) deconvolution. By controlling the axial positions of the microscope stage and an optically trapped bead independently, we can record the 3D blurring function at different depths. We find that the peak intensity collected from a single bead decreases with depth and that the width of the axial, but not the lateral, profile increases with depth. We present simple convolution and deconvolution algorithms that use the full depth-varying point-spread functions and use these to demonstrate a reduction of elongation artifacts in a reconstructed image of a 2 microm sphere.


An expanding landscape. Osteoporosis. Treatment options today.
Choices for osteoporosis therapy have expanded within the past 5 years. This article provides an overview of currently available therapy options. Exogenous estrogen can prevent and treat osteoporosis and is available in several delivery routes. Calcitonin is also designed to reduce bone loss in osteoporosis. Bisphosphonates such as alendronate prevent bone resorption by inhibiting osteoclasts and causing increased osteoclast cell death. Raloxifene is a selective estrogen receptor modulator and is the newest osteoporosis medication on the market. It may also have beneficial effects on breast cancer risk. All postmenopausal women should obtain 1,000 mg to 1,500 mg of calcium and 400 IU to 800 IU of vitamin D every day--regardless of any prescription therapy regimen for osteoporosis. They should also perform weight-bearing exercise, such as walking, for 20 to 30 minutes every day or for 1 hour three times a week.


Prevalence and predictors of elder abuse among older adults attending emergency departments: a prospective cohort study.
Elder abuse is associated with impaired physical and psychological health. It is, however, rarely identified in emergency departments (EDs). The objective was to determine the prevalence and the predictors of elder abuse among older adults visiting EDs. This prospective cohort study was conducted in eight Canadian EDs between May and August 2021. Patients were eligible if they were ≥ 65 years old, oriented to time, and with a Canadian Triage and Acuity Scale score 3, 4 or 5. In a private setting, participants were questioned directly about abuse as part of a larger questionnaire exploring ten non-medical problems. We used multivariable logistic regression to identify predictors of elder abuse. A total of 1061 participants were recruited (mean age: 77.1 (SD 7.6) years, female sex: 55.7%, lived alone: 42.5%). Patients mostly attended EDs for pain (19.6%), neurologic (11.3%) or cardiovascular (8.4%) symptoms. The most frequent pre-existing comorbidities were hypertension (67.2%), mental health conditions (33.3%) and cardiac insufficiency (29.6%). Mobility issues outside (41.0%) or inside their home (30.7%) and loneliness (29.4%) were also frequent. Fifty-four (5.1%) participants reported elder abuse, of which 34.3% were aware of available community-based resources. Identified predictors of elder abuse were female sex (OR 2.8 [95%CI 1.4; 5.6]), financial difficulties (OR 3.6 [95%CI 1.8; 7.3]), food insecurity (OR 2.7 [95%CI 1.2; 5.6]), need for a caregiver (OR 2.7 [95%CI 1.5; 5.0]) and at least one pre-existing mental health condition (OR 2.6 [95%CI 1.4; 4.9]). When questioned directly, 5.1% of older adults attending EDs reported experiencing abuse. Female sex, functional impairment, social vulnerability, and mental health comorbidities are associated with elder abuse. Given its importance and relatively high prevalence, ED professionals should have a low threshold to ask directly about elder abuse.


Refining the Implementation of a Hub-and-Spoke Model for TelePain Through Qualitative Inquiry.
The hub-and-spoke telehealth model leverages centrally located providers who utilize telehealth technology to bring specialized care to medically underserved areas. This model has the potential to promote equitable access to healthcare. However, few studies address how to facilitate the adoption and implementation of hub-and-spoke telehealth. We examined spoke site providers' experiences with TelePain, a national hub-and-spoke model of interdisciplinary chronic pain care, with a focus on improving future implementation. We conducted semi-structured individual interviews (20-45 min) with 27 VA spoke site providers via teleconferencing between August 2020 and February 2021. Interview transcripts were coded in Atlas.ti 8.0 using deductive (identified a priori and used to build the interview guide) and inductive (emerging) codes. Our analysis identified the following themes stressed by the spoke sites: (1) spoke sites needed to envision how TelePain services would work at their site before deciding to adopt; (2) TelePain implementation needed to fit into local existing care processes; (3) hub sites needed to understand spoke sites' context (e.g., via needs assessment) to tailor the services accordingly, and (4) hub-and-spoke sites needed to establish bidirectional communication. Our findings provide a practical guide to improve future rollout of hub-and-spoke telehealth models. Recommendations focus on the role of the hub site in promoting program adoption by (1) developing a clear and detailed marketing plan and (2) considering how the program can be adapted to fit the local spoke site context. To improve implementation, hub-and-spoke sites must establish ongoing and consistent bidirectional communication; this is particularly critical in the everchanging post-peak pandemic healthcare system. An important next step is the development of recommendations and guidelines for implementing hub-and-spoke telehealth, as well as examining pain outcomes for patients touched by this program.


Circum-Mediterranean phylogeography of a bat coupled with past environmental niche modeling: A new paradigm for the recolonization of Europe?
The isolation of populations in the Iberian, Italian and Balkan peninsulas during the ice ages define four main paradigms that explain much of the known distribution of intraspecific genetic diversity in Europe. In this study we investigated the phylogeography of a wide-spread bat species, the bent-winged bat, Miniopterus schreibersii around the Mediterranean basin and in the Caucasus. Environmental Niche Modeling (ENM) analysis was applied to predict both the current distribution of the species and its distribution during the last glacial maximum (LGM). The combination of genetics and ENM results suggest that the populations of M. schreibersii in Europe, the Caucasus and Anatolia went extinct during the LGM, and the refugium for the species was a relatively small area to the east of the Levantine Sea, corresponding to the Mediterranean coasts of present-day Syria, Lebanon, Israel, and northeastern and northwestern Egypt. Subsequently the species first repopulated Anatolia, diversified there, and afterwards expanded into the Caucasus, continental Europe and North Africa after the end of the LGM. The fossil record in Iberia and the ENM results indicate continuous presence of Miniopterus in this peninsula that most probably was related to the Maghrebian lineage during the LGM, which did not persist afterwards. Using our results combined with similar findings in previous studies, we propose a new paradigm explaining the general distribution of genetic diversity in Europe involving the recolonization of the continent, with the main contribution from refugial populations in Anatolia and the Middle East. The study shows how genetics and ENM approaches can complement each other in providing a more detailed picture of intraspecific evolution.


Comparison of the diagnostic performance of three ultrasound thyroid nodule risk stratification systems for follicular thyroid neoplasm: K-TIRADS, ACR -TIRADS and C-TIRADS.
To explore the diagnostic performance of the currently used ultrasound-based thyroid nodule risk stratification systems (K-TIRADS, ACR -TIRADS, and C-TIRADS) in differentiating follicular thyroid adenoma (FTA) from follicular thyroid carcinoma (FTC). Clinical data and preoperative ultrasonographic images of 269 follicular thyroid neoplasms were retrospectively analyzed. All of them were detected by Color Doppler ultrasound instruments equipped with high-frequency liner array probes (e.g. Toshiba Apoli500 with L5-14MHZ; Philips IU22 with L5-12MHZ; GE LOGIQ E9 with L9-12MHZ and MyLab Class C with L9-14MHZ). The diagnostic performance of three TIRADS classifications for differentiating FTA from FTC was evaluated by drawing the receiver operating characteristic (ROC) curves and calculating the cut-off values. Of the 269 follicular neoplasms (mean size, 3.67±1.53 cm), 209 were FTAs (mean size, 3.56±1.38 cm) and 60 were FTCs (mean size, 4.07±1.93 cm). There were significant differences in ultrasound features such as margins, calcifications, and vascularity of thyroid nodules between the FTA and FTC groups (P < 0.05). According to the ROC curve comparison analysis, the diagnostic cut-off values of K-TIRADS, ACR-TIRADS, and C-TIRADS for identifying FTA and FTC were K-TR4, ACR-TR4, and C-TR4B, respectively, and the areas under the curves were 0.676, 0.728, and 0.719, respectively. The difference between ACR-TIRADS and K-TIRADS classification was statistically significant (P = 0.0241), whereas the differences between ACR-TIRADS and C-TIRADS classification and between K-TIRADS and C-TIRADS classification were not statistically significant (P > 0.05). The three TIRADS classifications were not conducive to distinguishing FTA from FTC. It is necessary to develop a novel malignant risk stratification system specifically for the identification of follicular thyroid neoplasms.


Quality Assurance Investigations and Impurity Characterization during Upscaling of [177Lu]Lu-PSMAI&T.
[177Lu]Lu-PSMAI&T is widely used for the radioligand therapy of metastatic castration-resistant prostate cancer (mCRPC). Since this kind of therapy has gained a large momentum in recent years, an upscaled production process yielding multiple patient doses in one batch has been developed. During upscaling, the established production method as well as the HPLC quality control were challenged. A major finding was a correlation between the specific activity and the formation of a pre-peak, presumably caused by radiolysis. Hence, nonradioactive reference standards were irradiated with an X-ray source and the formed pre-peak was subsequently identified as a deiodination product by UPLC-MS. To confirm the occurrence of the same deiodinated side product in the routine batch, a customized deiodinated precursor was radiolabeled and analyzed with the same HPLC setup, revealing an identical retention time to the pre-peak in the formerly synthesized routine batches. Additionally, further cyclization products of [177Lu]Lu-PSMAI&T were identified as major contributors to radiochemical impurities. The comparison of two HPLC methods showed the likelihood of the overestimation of the radiochemical purity during the synthesis of [177Lu]Lu-PSMAI&T. Finally, a prospective cost reduction through an optimization of the production process was shown.


Black box optimization benchmarking of the GLOBAL method.
GLOBAL is a multi-start type stochastic method for bound constrained global optimization problems. Its goal is to find the best local minima that are potentially global. For this reason it involves a combination of sampling, clustering, and local search. The role of clustering is to reduce the number of local searches by forming groups of points around the local minimizers from a uniformly sampled domain and to start few local searches in each of those groups. We evaluate the performance of the GLOBAL algorithm on the BBOB 2009 noiseless testbed, containing problems which reflect the typical difficulties arising in real-world applications. The obtained results are also compared with those obtained form the simple multi-start procedure in order to analyze the effects of the applied clustering rule. An improved parameterization is introduced in the GLOBAL method and the performance of the new procedure is compared with the performance of the MATLAB GlobalSearch solver by using the BBOB 2010 test environment.


Inflammation-Targeting Mesenchymal Stem Cells Combined with Photothermal Treatment Attenuate Severe Joint Inflammation.
Current clinical therapeutic efficacy for the treatment of osteo- and rheumatoid-arthritis is obviously limited. Although mesenchymal stem cells (MSCs) are considered as a source of promising regenerative therapy, un-modified MSCs or genetically engineered MSCs injected in vivo restrict their clinical utility because of the low drug efficacy and unpredicted side effect, respectively. Herein, a strategy to enhance the migration efficacy of MSCs to inflamed joints via an inflammation-mediated education process was demonstrated. To reinforce the limited anti-inflammatory activity of MSCs, gold nano-star loaded with triamcinolone are conjugated to MSC. Furthermore, near-infrared laser-assisted photothermal therapy (PTT) induced by gold nano-star significantly elevate the anti-inflammatory efficacy of the developed drugs, even in advanced stage arthritis model. An immunological regulation mechanism study of PTT is first suggested in this study; the expression of the interleukin 22 receptor, implicated in the pathogenesis of arthritis, was downregulated in T lymphocytes by PTT, and Th17 differentiation from naïve CD4 T cell was inhibited. Collectively, inflammation-targeting MSCs conjugated with triamcinolone-loaded gold nano-star promote the repolarization of macrophages and decrease neutrophil recruitment in joints. In addition, Edu-MSCs-AuS-TA significantly alleviate arthritis-associated pain and improve general locomotor activity, and more importantly, induced cartilage regeneration even for severe stages of arthritis model. This article is protected by copyright. All rights reserved.


Magnetic mini-mover procedure for pectus excavatum II: initial findings of a Food and Drug Administration-sponsored trial.
The Magnetic Mini-Mover Procedure (3MP) uses a magnetic implant coupled with an external magnet to generate force sufficient to gradually remodel pectus excavatum deformities. This is an interim report of the evolution of the 3MP during a Food and Drug Administration-approved clinical trial. After obtaining Institutional Review Board approval, we performed the 3MP on 10 otherwise healthy patients with moderate to severe pectus excavatum deformities (age, 8-14 years; Haller index >3.5). Operative techniques evolved to improve ease of implantation. Patients were evaluated monthly by a pediatric surgeon and orthotist. Electrocardiograms were performed pre- and postoperatively. Sternal position was documented by pre- and postprocedure computed tomographic scan, interval chest x-ray, depth gauge, and interval photographs. There was no detectable effect of the static magnetic field on wound healing or cardiopulmonary function. No detectable injuries and minimal skin changes resulted from brace wear. Operative techniques evolved to include a custom sternal punch and a flexible guide wire to guide the posterior plate into position behind the sternum, reducing outpatient operating time to one-half hour. In 9 patients, the procedure was performed as an outpatient basis; and 1 patient was observed overnight. Three patients required evacuation of retained pleural air postoperatively, and 2 required an outpatient revision. A custom-fitted orthotic brace (Magnatract) was extensively modified to increase user friendliness and functionality while incorporating several novel functions: a screw displacement mechanism so patients can easily self-adjust magnetic force, a miniature data logger to measure force and temperature data every 10 minutes, and an interactive online Web portal for remote patient evaluation. All attempts to quantitate sternal position (radiographic, fluid volume, and depth gauge) were inadequate. Visual assessment remains the best indicator. In this interim report, the 3MP appears to be a safe, minimally invasive, outpatient, cost-effective alternative treatment of pectus excavatum. Outcomes will be reported upon the completion of this phase II clinical trial.


Reliability of the Behavioral Assessment Scale of Oral Functions in Feeding.
Interrater and test-retest reliability of the Behavioral Assessment Scale of Oral Functions in Feeding were computed for two separate samples of severely and profoundly handicapped students having oral-motor and feeding disorders. Reliability was assessed using the intraclass correlation-generalizability theory approach and resulted in coefficients ranging from .68 to .84. These values were considered only marginally acceptable by current standards of instrument development advocated in the behavioral sciences. This paper discusses the difficulty in developing psychometrically satisfactory assessment instruments for use with the severely and profoundly developmentally disabled and gives implications for practice and future research.


Studying the relationship between the Lund Mackay score and response to medical treatment in patients with chronic sinusitis.
One of the most common reasons for patients to visit a doctor is Sinusitis. Treatment of this disease involves a wide range of topical and systemic drugs, if it left untreated, surgery and sinus drainage will be the only choice. Due to symptoms and problems caused by chronic sinusitis and its treatment, as well as the need for an appropriate solution to reduce this, the present study was conducted to investigate the relationship between The Lund Mackay score and response to medical treatment in patients with chronic sinusitis. The present study was performed cross-sectionally on 150 patients referred to Khatamul- Anbia Hospital in Zahedan for whom the diagnosis of chronic sinusitis was confirmed and met the study criteria. Demographic data and clinical signs of patients were recorded and for based on CT scan, The Lund Mackay score was evaluated. Patients were treated for 4 to 6 weeks and finally re-evaluated for symptoms and response to treatment. Data were analyzed using SPSS software version 24, McNemar test, Mann-Whitney and other necessary tests for descriptive statistics. A significance level of 0.05 was considered. 3.55% of patients were male (83 patients) and 7.44% were female (67 patients). The mean score of the Lund Mackay in the present study was 92.11 with a standard deviation of 2.3. Symptoms of olfactory dysfunction, sinus pain, nasal obstruction and nasal discharge showed significant improvement after treatment (p <05.0). Based on the results obtained at the end of the study, the presence of nasal polyps (p = 001.0) and nasal obstruction (p = 003.0), after the end of the treatment period, showed a significant relationship with the response to treatment. In general, this study suggested that the mean score of The Lund Mackay had a significant positive relationship with the severity of patients' clinical symptoms and the severity of sinusitis. Therefore, it can be considered as a suitable criterion in diagnostic and therapeutic evaluations of patients.


Physiological correlates of symbiont migration during bleaching of two octocoral species.
Perturbed colonies of Phenganax parrini and Sarcothelia sp. exhibit migration of symbionts of Symbiodinium spp. into the stolons. Densitometry and visual inspection indicated that polyps bleached while stolons did not. When migration was triggered by temperature, light and confinement, colonies of Sarcothelia sp. decreased rates of oxygen formation in the light (due to the effects of perturbation on photosynthesis and respiration) and increased rates of oxygen uptake in the dark (due to the effects of perturbation on respiration alone). Colonies of P. parrini, by contrast, showed no significant changes in either aspect of oxygen metabolism. When migration was triggered by light and confinement, colonies of Sarcothelia sp. showed decreased rates of oxygen formation in the light and increased rates of oxygen uptake in the dark, while colonies of P. parrini maintained the former and increased the latter. During symbiont migration into their stolons, colonies of both species showed dramatic increases in reactive oxygen species (ROS), as visualized with a fluorescent probe, with stolons of Sarcothelia sp. exhibiting a nearly immediate increase of ROS. Differences in symbiont type may explain the greater sensitivity of colonies of Sarcothelia sp. Using fluorescent probes, direct measurements of migrating symbionts in the stolons of Sarcothelia sp. showed higher levels of reactive nitrogen species and lower levels of ROS than the surrounding host tissue. As measured by native fluorescence, levels of NAD(P)H in the stolons were unaffected by perturbation. Symbiont migration thus correlates with dramatic physiological changes and may serve as a marker for coral condition.


Neurological distress in Togolese newborn: Prevalence, causes and clinical features.
The transition from fetal to neonatal life during birth is difficult for all babies. We aim to analyze the demography, clinical presentation, causes, and outcome of neurologically distressed newborns. We reviewed a total of 615 newborns files admitted with life threatening condition. Amongst them, 453 had presented neurological distress syndrome. Only cases with severe neurological impairment (Apgar Score System [ASS] ≤6) with no other associated injury were included in the study group. The study covered a period from January to December 2011 and located in pediatric intensive care unit. The information regarding clinical presentation, condition of birth, causes of distress, and outcome were analyzed. Neonate examination had been conducted by neonatologist and pediatric neurologist. The sample included 272/453 (60.04%) males and 181/453 (39.96%) females. Newborns were aged from 1 to 14 days. The incidence of neurological distress amongst all admissions was 453/615 (73.65%). Clinical signs were weakness of primary reflexes (86.70%), non reactivity (78.19%), flaccid muscle tone (59.49%) and impaired consciousness (32.29%). On Apgar score, 73 (20.68%) had a score from 0 to 3; 234 (66.29%) had a score 4-6 in the first minute of life. A total of 307 (86.97%) newborns had been resuscitated at birth during the first five minutes. Death rate was 35.69%. Asphyxia (51.27%) and neonatal infection (43.34%) were the most common causes of death. These results show that much effort remains to be done in obstetric care, resuscitation management and improvement in neonatal infection care.


Knowledge for knowledge translation: the role of the Cochrane Collaboration.
Knowledge-translation (KT) activities, including continuing education, should be informed by the totality of available research evidence. Systematic reviews are a generic methodology used to synthesize evidence from a broad range of research methods addressing different questions. Over the past decade, there has been a dramatic increase in the availability of systematic reviews that could support KT activities. However, the conduct of systematic reviews is technically challenging, and it is not surprising that the quality of available reviews is variable. In addition, unless attempts are made to update systematic reviews, they rapidly become out of date. The Cochrane Collaboration is a unique, worldwide, not-for-profit organization that aims to help people make well-informed decisions about all forms of health care by preparing, maintaining, and promoting the accessibility of systematic reviews of the effects of health care interventions. Globally, over 13, 000 consumers, clinicians, policymakers, and researchers are involved with The Cochrane Collaboration and have to date produced over 2, 500 systematic reviews that can be used to inform KT activities. The Cochrane Collaboration publishes its reviews quarterly in The Cochrane Library. Cochrane reviews have been used to develop a number of KT-derivative products for professionals, consumers, and policymakers. Whereas most Cochrane Review groups focus on specific clinical areas, the Cochrane Effective Practice and Organisation of Care Group undertakes reviews of interventions to improve health care delivery and health care systems, including reviews of different KT activities. We summarize the activities of The Cochrane Collaboration and how these can contribute to KT activities.


[The comparative study of bioelectronic brain activity at the drug and Internet-addiction].
The comparative estimation of the bioelectric brain activities at different drug (heroin, opium, toxic organic join, home chemistry) and internet addiction are studied. These data can be interest for problem of general and specific mechanism of the influence of different factors, causing the addiction, on neirofisiological and neirochemical processes.


The absence of quinoprotein alcohol dehydrogenase in Acinetobacter calcoaceticus.
It is shown that the unusual NAD(P)+-independent quinoprotein alcohol dehydrogenase, said previously to be responsible for oxidation of ethanol during growth of Acinetobacter calcoaceticus LMD 79.39, was in fact isolated from an unidentified organism which contained cytochrome c and which has now been lost. Several genuine strains of A. calcoaceticus do not contain cytochrome c nor do they contain a quinoprotein alcohol dehydrogenase. The enzyme responsible for ethanol oxidation in these bacteria is an inducible NAD+-linked alcohol dehydrogenase.


[Three-dimensional visualization of the brain ependyma and tanycytes].
The aim of this investigation was to develop an integrated approach to spatial reconstruction of the cells lining the ventricles of the brain using confocal laser microscopy and immunocytochemical reaction to vimentin. The work was performed on paraffin sections of rat brain of different thickness (5 and 10 microm). To visualize the immunocytochemical reaction the fluorescent dyes in the visible range were selected: SYTOX Green selectively staining the nucleus and indocarbocyanin (Cy-3) conjugated with streptavidin. As a result of testing of various processing conditions, the protocol which allows to receive an intensive staining of the structures was developed. The set of fluorochromes proposed in confocal laser microscopy allows to separate easily the channels, to study the structures independently, if needed, and does not require the use of an expensive ultraviolet laser.


Direct Oral Anticoagulants in Cardioversion: A Review of Current Evidence.
Direct oral anticoagulants (DOACs) are recommended for the prevention of stroke or systemic embolism in nonvalvular atrial fibrillation. Dabigatran, rivaroxaban, apixaban, and edoxaban represent possible alternatives to warfarin in the setting of cardioversion. A literature review was conducted to evaluate the safety and efficacy of DOAC use pericardioversion. A PubMed and MEDLINE search through August 2017 was conducted using the following search terms alone or in various combinations: dabigatran, rivaroxaban, apixaban, edoxaban, betrixaban, DOAC, NOAC, TSOAC, cardioversion. All English-language, human studies comparing the safety and efficacy of DOACs with that of other anticoagulants in the setting of cardioversion were eligible for inclusion. References from published articles were reviewed for additional relevant citations for study inclusion. Four retrospective and 2 prospective trials comparing DOACs with warfarin were identified. The majority of studies included patients undergoing electric cardioversion. Based on current evidence, the DOACs perform similarly to warfarin in the prevention of stroke and systemic embolism, and bleeding rates are comparable. DOACs may be an attractive alternative to warfarin because of fast onset of action, potentially reducing delay to cardioversion. More robust studies are needed in patients with renal dysfunction and patients undergoing pharmacological cardioversion.


Lower risk of fractures under methylphenidate treatment for ADHD: A dose-response effect.
Methylphenidate (MP), a widely used and abused stimulant medication for ADHD, negatively affects bone mass. However, previous epidemiological studies demonstrated that MP is not associated with increased incidence of fractures in children, and may even have a protective effect due to behavior modification. This study aimed to investigate the association between MP and fracture risk in a retrospective cohort of healthy military recruits, aged 18-25, with at least 1 year of service between 2008 and 2017. Subjects were divided into five groups: subjects without ADHD; untreated subjects with ADHD; and subjects with ADHD and prescriptions of 1-90, 91-180, or 181+ tablets during the study period. The primary outcome was at least one fracture diagnosis during the study. Among 682,110 subjects (409,175 men [60%]), 50,999 (7.5%) had fractures. MP was used by 1,681 (0.4%) men and 2.828 (1%) women. The fracture rates in the no ADHD, untreated ADHD, ADHD 0-90, ADHD 91-180, and ADHD 181+ groups were 10.4%, 16.4%, 8.7%, 4.8% and 5.8% in men, and 3.6%, 7.1%, 4.6%, 4.4% and 3% in women, respectively. Multivariate regression analysis confirmed an inverse dose-response association between MP and fractures in men (p < 0.001). In women, untreated ADHD was associated with a significantly higher fracture risk, compared to healthy controls (OR = 1.82, p < 0.001). The study confirms previous literature and demonstrates an inverse dose-response association between MP and fracture risk in men. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:3328-3333, 2018.


Erythema annulare centrifugum-like mycosis fungoides.
A considerable number of recent reports have documented mycosis fungoides resembling many other dermatoses. Due to highly variable presentations and the sometimes non-specific nature of histological findings, an accurate diagnosis of mycosis fungoides can be difficult. Erythema annulare centrifugum-like mycosis fungoides with a variety of annular, polycyclic erythematous skin lesions is a recently recognized atypical manifestation of mycosis fungoides, and only a few cases have been reported to date.


Root cementum may modulate gene expression during periodontal regeneration: a preliminary study in humans.
Previous data demonstrated that root cementum may affect periodontal regeneration. As such, this study aimed to explore further possible mechanisms involved in this process by investigating in humans whether root cementum modulates gene expression in the regenerating tissue formed under membrane-protected intrabony defects. Thirty subjects with deep intrabony defects (> or =5 mm; 2- or 3-wall) were selected and assigned to the control or test group. The control group received scaling and root planing with the removal of granulation tissue and root cementum; the test group underwent removal of granulation tissue and soft microbial deposits by cleaning the root surface with a microbrush and saline solution, aiming at cementum preservation. Guided tissue regeneration (GTR) was applied to both groups. Twenty-one days later, the newly formed tissue under the membrane was assessed for the expression of the following genes: alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), platelet-derived growth factor-alpha (PDGFA), bone sialoprotein (BSP), and basic fibroblast growth factor (bFGF). Data analysis demonstrated that mRNA levels for PDGFA, BSP, and bFGF were higher in the sites where root cementum was kept in place compared to the sites where root cementum was removed completely as part of the periodontal therapy (P <0.05); in contrast, OCN levels were lower (P <0.05). No difference for ALP or OPN was observed between the control and test groups (P >0.05). Root cementum may modulate the expression of growth and mineral-associated factors during periodontal regeneration.


Gold - Old Drug with New Potentials.
Research into gold-based drugs for a range of human diseases has seen a revival in recent years. This article reviews the most important applications of gold products in different fields of human pathology. Au(I) and Au(III) compounds have been re-introduced in clinical practice for targeting the cellular components involved in the onset and progression of viral and parasitic diseases, rheumatoid arthritis and cancer. After some brief historical notes, this article takes into account the applications of gold compounds against Mycobacterium tuberculosis, and also in tuberculosis and in rheumatoid arthritis treatment. The use of gold containing drugs in the cure of cancer are then considered, with special emphasis to the use of nanoparticles and to the photo-thermal cancer therapy. The use of colloidal gold in diagnostics, introduced in the last decade is widely discussed. As a last point a survey on the adverse effects and on the toxicity of the various gold derivatives in use in medicine is presented. In this review, we described the surprisingly broad spectrum of possible uses of gold in diagnostics and in therapeutic approaches to multiple human diseases, ranging from degenerative to infectious diseases, and to cancer. In particular, gold nanoparticles appear as attractive elements in modern clinical medicine, combining high therapeutic properties, high selectivity in targeting cancer cells and low toxicity.


Cleft lip and palate: technical strategies for the primary palatoplasty.
Surgical procedures in cleft lip and palate repair are continuously evolving. In the international literature, many guidelines exist dealing with different timings and surgical approaches. The authors present a technical strategy on primary palatoplasty and the guidelines for the surgical management of cleft lip and palate adopted by the Department of Maxillo-Facial Surgery of the Università "La Sapienza" of Rome. This approach has been developed to allow a physiological facial growth and to preserve the essential main features of the stomatognathic system enclosing phonation and swallowing. Moreover, the authors present their own surgical technique for primary palate repair at 24 to 48 months with the galea-pericranium free flap.


[Retroperitoneal fibrosis in a patient treated with bromocriptine for a prolactinoma].
We present one case of retroperitoneal fibrosis occurring in a patient presenting with a prolactinoma identified five years previously and treated with bromocriptine since then. Bromocriptine, an ergot derivative with a dopaminergic action, seems to be the cause of the fibrosis in this patient.


Fire and the spread of flowering plants in the Cretaceous.
We suggest that the spread of angiosperms in the Cretaceous was facilitated by novel fire regimes. Angiosperms were capable of high productivity and therefore accumulated flammable biomass ('fuel') more rapidly than their predecessors. They were capable of rapid reproduction, allowing populations to spread despite frequent disturbance. We evaluate the evidence for physical conditions conducive to fires in the Cretaceous. These included high temperatures, seasonally dry climate and higher atmospheric oxygen than current levels. We evaluate novel properties of angiosperms that contributed to rapid biomass accumulation, and to their ability to thrive in frequently disturbed environments. We also review direct evidence for Cretaceous fires. Charcoal mesofossils are common in Cretaceous deposits of the Northern Hemisphere. Inertinite, the charcoal component of coal, is common throughout the Cretaceous and into the Palaeocene, but declined steeply from the Eocene when angiosperm-dominated forests became widespread. Direct and indirect evidence is consistent with angiosperms initiating novel fire regimes, promoting angiosperm spread in the Cretaceous. Several traits are consistent with frequent surface fires. We suggest that forest was slow to develop until the Eocene, when fire activity dropped to very low levels. The causes and consequences of fires in the deep past warrant greater attention.


Association between paediatric intraoperative anaesthesia handover and adverse postoperative outcomes.
To determine whether intraoperative handover of patient care from one anaesthesia clinician to another was associated with an increased risk of adverse postoperative outcomes during paediatric surgeries. A retrospective, population-based cohort study (1 April 2013-1 June 2018) at an academic medical centre. Intraoperative handover of care between pairs of anaesthesia clinicians from one care provider to another compared with no handover of anaesthesia care. The primary outcome was a composite of all-cause mortality and major postoperative morbidity within 30 days after surgery. Secondary outcomes included individual components of the primary outcome and 30-day hospital readmission. Inverse probability of exposure weighting using propensity scores for intraoperative handovers was calculated. Weighted logistic regression was used to determine the association between intraoperative anaesthesia handovers and outcomes. 78 321 paediatric surgical cases (n=5411 with handovers) were included for analysis. Patients were predominantly male (56.5%) with a median age of 6.56 (IQR: 2.65-12.53) years and a median anaesthesia duration of 76 (IQR: 55-126) min. In the weighted sample, the odds of the primary outcome (OR: 0.92; 95% CI 0.75 to 1.13; p=0.43), any morbidity (OR: 0.93; 95% CI 0.75 to 1.16; p=0.515), all-cause mortality (OR: 0.8; 95% CI 0.37 to 1.73; p=0.565) or 30-day readmission following surgery (OR: 0.99; 95% CI 0.84 to 1.18; p=0.95) did not significantly differ among surgeries with and without handovers. Among paediatric patients undergoing surgery, intraoperative anaesthesia handovers were not associated with adverse postoperative outcomes, after accounting for relevant covariates. These findings provide a preliminary perspective on the role of intraoperative handovers as a care-neutral event, with implications for improving safety.


Internet-based self-help treatment for panic disorder: a randomized controlled trial comparing mandatory versus optional complementary psychological support.
Panic disorder (PD) is one of the most common psychiatric disorders. Web-based self-help treatments for PD have had promising results. These online treatments seem to have larger effect sizes (ESs) when professional support is added. However, the amount of support or how it should be administered is not yet clear. The aim of this trial was to study two ways of administering psychological support provided by phone as a part of Internet-based self-help treatment for PD based on cognitive behavioral therapy. Seventy-seven participants diagnosed with PD were randomly assigned to one of three experimental conditions: a waiting list control group; a treatment group with non-scheduled psychological support; or a treatment group with scheduled psychological support. PD symptoms of participants who received treatment improved significantly compared to the control group (mean ES d = 1.18, p < .05). In addition, there were statistically and clinically significant differences between treatment groups (Mean difference = -3.20, p = .005, 95% CI [-5.62, -.79]). The scheduled group showed a larger ES, a lower dropout rate, and better adherence to treatment than the non-scheduled group. Scheduled support seems to be indicated for patients who seek Web-based treatment for PD, and their symptoms of panic, anxiety, and depression improve at post-treatment and six-month follow-up. In contrast, when support depends on patient demand, they receive less support and so, the therapeutic effect is poorer.


The role of chest CT in management of asymptomatic SARS-CoV-2 infections: A longitudinal multi-center study in Chongqing, China.
Background: Multiple societies including the Fleischner Society do not recommend that CT is routinely used in asymptomatic SARS-CoV-2 infections; however, this advice is based on the limited evidence. In this study, we aim to confirm whether it is necessary to do CT scans in SARS-CoV-2 asymptomatic infections by summarizing the longitudinal chest CT and clinical features of asymptomatic SARS-CoV-2 infections. Methods: A total of 33 individuals (14 men and 19 women) with asymptomatic SARS-CoV-2 infections were retrospectively enrolled. Clinical data of CT positive and negative groups were compared. Longitudinal chest CT scans were reviewed for CT features and analyzed for temporal change. Results: Thirty-two (97%) individuals had positive results for first RT-PCR testing. For clinical data, only monocyte count showed a significant difference between CT positive and negative groups. For first chest CT, only eighteen (54.5%) individuals had abnormal manifestations, common CT features were GGO (88.9%) and consolidation (33.3%), the median number of segments involved was 3.0 (1.0-7.5). No case in CT negative group was abnormal on the follow-up CT. Three patterns of evolution throughout series of CT were observed in CT positive group, including gradual improvement (12, 66.7%), mismatch to improvement (3, 16.7%) and mild progression to improvement (3, 16.7%). On last CT scans, most cases had radiographic improvement but residual abnormalities. Significant differences were exhibited in density, long diameter, number of lung segments involved, and percentage of consolidation between the first and last CT scans. All cases had stable conditions and finally confirmed negative for SARS-CoV-2 RT-PCR tests without developing into severe pneumonia. Conclusion: Considering poor performance of CT in screening, stable conditions during followup, and good outcomes in asymptomatic SARS-CoV-2 infections, we confirm that it is unnecessary to do CT scans in asymptomatic SARS-CoV-2 infections.


[Morphofunctional criteria for the choice of alimentary mixture ingredients for intra-intestinal administration].
Morpho-functional changes in the intestine after application of highly caloric nutritional mixtures of different composition have been investigated in experiments on polyfistulous dogs in autoperfusion regimen. It was shown that in case of "element" mixture application the impairment of intestinal function is accompanied by morphological changes in epitheliocyte structure and intravascular disturbances. The optimal conditions of nutrient assimilation were revealed, using highly caloric mixtures with basic nutrient content and poly-, oligo- and monomer rations proportional to chyme.


New interpretation of the palate of Pterosaurs.
On the basis of a new, three-dimensionally preserved specimen of the Early Jurassic pterosaur Dorygnathus banthensis we present a reinterpretation of the pterosaur palate. The hard palate is formed by the extensive palatal plate of the maxilla and not by the palatine as has been generally reconstructed. This palatal plate of the maxilla emarginates the choana rostrally and rostrolaterally as in other archosaurs and lepidosaurs. The longitudinally elongate and dorsoventrally flat palatine in Dorygnathus is an isolated bone caudal to the palatal plate of the maxilla and morphologically and topographically it resembles that of crocodilians and birds, respectively. The palatine separates the choana laterally from the suborbital fenestra demonstrating the homologous nature of the (primary) choana in all archosaurs and lepidosaurs. Our study indicates that in basal pterosaurs the pterygo-ectopterygoid fenestra existed caudal to the suborbital fenestra, which became confluent with the adductor chamber in pterodactyloids thereby increasing the relative size of the adductor chamber and hence the mass of the jaw adductors. The choana in basal pterosaurs was relatively small compared with the interpterygoid vacuity. With increasing rostroventral inclination of the quadrates in more derived pterosaurs, the interpterygoid vacuity was reduced considerably, whereas the choana increased in size. This exceptional Dorygnathus specimen also shows a hitherto unknown pair of fenestrae situated at the palatal contact of the premaxilla-maxilla and might represent the aperture for the vomeronasal organ.