Redo mitral surgery after coronary artery bypass grafts under hyperkalemic hypothermia using thoracotomy and axillary artery cannulation in a patient with functioning bilateral internal thoracic arteries and atheromatous aorta.
Redo mitral valve surgery using resternotomy after coronary artery bypass grafting (CABG) is challenging as previous CABG with patent internal thoracic artery (ITA) poses a risk of injury due to dense adhesion. It is paramount to have alternative method to minimize this risk. We report a case of redo mitral and tricuspid valve repair via right thoracotomy under hypothermia and systemic potassium administration with axillary artery cannulation in a patient after CABG with patent bilateral ITA grafts crossing over the sternum. Herein, critical dissection around the aorta and functioning ITA grafts was avoided by performing the procedure under systemic hypothermia via thoracotomy. Furthermore, considering the presence of atheroma in the aorta, the axillary artery was used as a perfusion route to prevent stroke events. Postoperative course was uneventful and echocardiography demonstrated preserved cardiac function. Performing axillary artery cannulation and right thoracotomy under hypothermic cardiac arrest with systemic hyperkalemia without clamping the patent bilateral ITAs and aorta allowed us to perform redo mitral valve surgery after CABG without major postoperative cardiac or cerebral complications.


Ultra-low-loaded Ni-Fe Dimer Anchored to Nitrogen/Oxygen Sites for Boosting Electroreduction of Carbon Dioxide.
Single-atom catalysts (SACs), as a novel emerging category in heterogeneous catalysis, have exhibited superb activity and selectivity within the scope of many catalytic reactions, originating from their nature of atomic dispersion. However, they are not appropriate for more complicated reactions that benefit from multi-metal promotion, such as the carbon dioxide reduction reaction (CO2 RR). Atomic pair catalysts can provide a synergistic effect to break the intrinsic activity limit. Herein, inspired by theoretical prediction, a hetero-paired atomic-site catalyst (Ni/Fe-N/O-C) was developed for CO2 RR. Typically, the trace-amount-loaded double-atom-site catalysts exhibited outstanding turnover frequencies (≈460 s-1 ) surpassing reported ones by far. Interestingly, the loaded metal contents of the three M-N/O-C samples were extremely low, and Ni/Fe-N/O-C exhibited greatly improved durability compared with pure Ni-N/O-C or Fe-N/O-C and excellent CO selectivity above 80 % within a broad potential window of -1.4 to -1.7 V (vs. saturated calomel electrode, 99.8 % at -1.5 V). The superb performance of diatomic-site catalysts was attributed to the adjusted local environment and electron structure of the active center, which could decrease the reaction barrier of *COOH formation. This work presents new insights into manipulating electrocatalytic performance for the development of more sophisticated active sites.


Histopathology of the aortic valve in patients with a previous history of acute rheumatic fever. An analysis of 63 surgical specimens.
In a series of 63 surgical patients with a positive history of rheumatic fever and whose aortic valve was removed either singly or in combination with other valves, the histological examination of the aortic valves showed functional lesions in 22 cases (35%). Organic lesions of inflammatory origin, destruction of the architecture with scarring and presence of hypertrophic vessels, were observed in 19 valves (30%). The other cases were doubtful. This ratio was identical in uni- and plurivalvular involvement. Anatomic aspects and significance of microscopic lesions of the aortic valves were discussed. The role of microthrombi and turbulent flow in the pathogenesis of the functional lesions is stressed. The authors conclude that there is no correlation between the anatomic aspects of the aortic valve deformity and the presence of histologically proven organic lesions of inflammatory origin. This provides support to the current opinion that rheumatic carditis is mainly a disease of the mitral valve.


Correction: Sustained functional benefits after a single set of injections with abobotulinumtoxinA using a 2-mL injection volume in adults with cervical dystonia: 12-week results from a randomized, double-blind, placebo-controlled phase 3b study.
[This corrects the article DOI: 10.1371/journal.pone.0245827.].


RETRACTED: Correlation of Parameters of Endogenous Opioid System with Personality Traits and Anxiety Level in Patients with Mitral Valve Prolapse.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editor-in-Chief The authors have plagiarized part of a paper that had already appeared in Neurochemistry" (Russian), 2000.V.17, No2, pp.150-156 and Cell-surface aminopeptidases: basic and clinical aspects», P.413-415, ICS 1218. One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process."


Joint-level coordination patterns for split-belt walking across different speed ratios.
Locomotion is a highly flexible process, requiring rapid changes to gait due to changes in the environment or goals. Here, we used a split-belt treadmill to examine how the central nervous system coordinates a novel gait pattern. Existing research has focused on summary measures, most often step lengths, when describing changes induced while walking on the split-belt treadmill and during subsequent aftereffects. Here, we asked how the nervous system adjusts individual joint motions and the coordination pattern of the legs when people walk with one leg moving at either 2×, 3×, or 4× the speed of the other leg. We found that relative to tied-belt walking, split-belt perturbations change the timing relationships between the legs while most joint angle peaks and range of motion change little. The kinematic changes over the course of adaptation (i.e., from the beginning to end of a single split-belt walking bout) were subtle, particularly when comparing individual joint motions. The magnitude of the belt speed differences impacted intralimb coordination but did not produce consistent differences in most other measures. Most significant changes in kinematics occurred in the fast leg. Overall, interlimb timing changes drove a large proportion of the differences observed between tied-belt and split-belt gaits. Thus, it appears that the central nervous system can produce novel gait patterns through changes in coordination between legs that lead to new configurations at significant time points. These patterns can use within-limb and within-joint patterns that closely resemble those of normal walking.NEW & NOTEWORTHY We studied how the nervous system coordinates limb movements during asymmetric gait. Using a split-belt treadmill, we found that most changes in motion occurred when comparing motions between limbs, rather than among joints within a limb. Individual joint patterns resembled speed-matched comparisons, but this meant that joint movements became asymmetric during split-belt walking. These findings demonstrate that the nervous system can use consistent joint motions that are reconfigured in time to achieve new gait patterns.


Visualizing an emotional valence map in the limbic forebrain by TAI-FISH.
A fundamental problem in neuroscience is how emotional valences are represented in the brain. We know little about how appetitive and aversive systems interact and the extent to which information regarding these two opposite values segregate and converge. Here we used a new method, tyramide-amplified immunohistochemistry-fluorescence in situ hybridization, to simultaneously visualize the neural correlates of two stimuli of contrasting emotional valence across the limbic forebrain at single-cell resolution. We discovered characteristic patterns of interaction, segregated, convergent and intermingled, between the appetitive and aversive neural ensembles in mice. In nucleus accumbens, we identified a mosaic activation pattern by positive and negative emotional cues, and unraveled previously unappreciated functional heterogeneity in the D1- and D2-type medium-spiny neurons, which correspond to the Go and NoGo pathways. These results provide insights into the coding of emotional valence in the brain and act as a proof of principle of a powerful methodology for simultaneous functional mapping of two distinct behaviors.


The development, inter-rater agreement and performance of a hierarchical procedure for setting the rest-interval in actigraphy data.
The aim of this study was to develop and empirically test a hierarchical procedure for defining rest intervals in actigraphy data. This is a two-part study. The aim of study 1 was to identify common practices for setting rest intervals in actigraphy research and investigate whether standardized guidelines for setting the rest interval exist, as a base to develop a new procedure for defining rest intervals in actigraphy. The aim of study 2 was to empirically test this procedure (The Rest Interval Setting, RISE Procedure). The RISE procedure was applied to a dataset of 537 nights from the sleep study SLEEPIC. Participants (N = 55) were aged 19-33 (M = 22.7, SD = 3.0). Study 1: Structured overview of the methods used to correct actigraphy data. Study 2: Three scorers independently applied the RISE procedure to the dataset. Study 1 demonstrated that methods and reporting practices are inconsistent and that there is a need for a standardized procedure for setting the rest interval. The results in study 2 revealed that using the new procedure for setting rest intervals provided high agreement between scorers for both rest onsets (α= 0.975) and offsets (α= 0.998). Applying the procedure to the dataset resulted in a shortening of the rest interval by 36 min and 19 s on average. There were significant changes (p < 0.001) in all sleep estimate outcomes after applying the RISE procedure. Methods for processing and reporting actigraphy data are highly inconsistent across studies. Here we present empirical support for a new standardized procedure for setting the rest interval, which is likely to improve transparency and reproducibility in achigraphy research.


Bioaccessibility dependence of dietary exposure to dichlorodiphenyltrichloroethane and its metabolites and hexachlorocyclohexane isomers and their induced health risk: A case study in Beijing City, China.
Bioaccessibility is essential for evaluating dietary intake of contaminants. However, there is insufficient information on the dependence of dietary intake and risk assessment of dichlorodiphenyltrichloroethane and its metabolites (DDXs) and hexachlorocyclohexane isomers (HCHs) on bioaccessibility. Here, we investigated the bioaccessibilities of DDXs and HCHs in various foods and their influences on assessing exposure in the residents of Beijing City, China. Forty-three major foods in five types (fruit, vegetables, cereals, aquatic food, and meat) were sampled, and the bioaccessibility of DDXs and HCHs was evaluated using a static in vitro gastrointestinal digestion model. The bioaccessibility of DDXs in different food types ranked in the order of meat > vegetables > fruit > cereals > aquatic food, with mean ± standard deviation values of 62.2 ± 22.1%, 20.5 ± 10.6%, 12.4 ± 3.66%, 11.2 ± 9.69%, and 10.7 ± 4.97%, respectively. The highest average bioaccessibility of HCHs was found in meat (83.4 ± 14.2%), followed by fruit (41.0 ± 12.5%), vegetables (37.6 ± 18.1%), aquatic foods (24.2 ± 9.22%), and cereals (8.73 ± 4.07%). The estimated daily intakes (EDI) of the sum of DDXs and the sum of HCHs based on the bioaccessible concentration were only about 17% and 55% of the total EDI based on the residual concentration, respectively. Meat was found to play a more important role in EDI after bioaccessibility correction. The proportion of the population with potential non-carcinogenic and carcinogenic risks markedly decreased when considering bioaccessibility. It was concluded that bioaccessibility should be integrated into dietary exposure evaluation.


Effect of topical indomethacin on UVR-induced redness and prostaglandin E levels in sunburned guinea pig skin.
Prostaglandin E (PGE) levels in the skin have been shown to be elevated during the 24 hr. period following exposure of guinea pig skin to ultraviolet radiation from 280-320 nm in the so-called UVB or "sunburn spectrum". The development of increased PGE levels paralleled the development of the delayed phase of erythema. When applied immediately after UVB exposure, one topical application of 2.5% Indomethacin (IM) simultaneously decreased the redness and PGE levels in the skin to near normal within one hr. of treatment. The IM effect persisted for approximately 24 hrs. By 48 hrs. the PGE level in the sunburned skin was near normal whether or not the skin had been treated with IM. The redness which was evident at 48 hrs. did not respond to additional topical IM treatment. This suggests that a substance(s) other than PGE may be involved in this latter portion of UVB-induced erythema. A major role for PGE as an early mediator or potentiator of UVB-induced erythema has been deomonstrated. Any involvement of PGE with UVB-induced cell death or alterations in DNA synthesis seems unlikely.


[Gender identity disorder: challenges and specificity in the treatment of requests for sexual reassignment].
Gender identity disorder is defined as a permanent desire to relieve one's own sexual features to acquire the sexual features and line to life of the opposite sex. The diagnosis is based on the psychiatric evaluation and treatment on an interdisciplinary approach by endocrinologists, surgeons and psychiatrists, and can be conceptualized into distinct phases: diagnostic evaluation, real life experience, hormonal treatment and surgery. Multiples challenges have to be faced, especially by the psychiatrist who follows the patient during the whole process.


A case of bacteremia caused by Hafnia paralvei.
The genus Hafnia, a member of the Enterobacteriaceae, is widespread in nature and rarely causes human infection. We describe a case of an 85-year-old Japanese man hospitalized consequent to suspected cholecystitis, in which Hafnia sp. was recovered from the blood culture concomitantly with Enterococcus faecalis. Sequencing of the 16S ribosomal RNA gene sequence and phenotyping with ID 32 E revealed that the recovered Hafnia sp. was considered to be Hafnia alvei genomosp. 2 (ATCC 29927), recently reclassified as Hafnia paralvei. The patient recovered uneventfully with antimicrobial therapies.


Look left, look right: censoring in clinical research.
In this methodology editorial, the problem of censored survival (or time-to-event) data in clinical research is discussed. In case of censored observations, part of the observation time for some participants in a study is unobserved, which means that measures such as an average survival time cannot be calculated. Instead, censored survival time should explicitly be accounted for in the analysis of a study, for example using the Kaplan-Meier method. Implications of censoring and how to deal with it in the analysis of a study or when reading a research paper are discussed.


Rheological and mucoadhesive characterization of poly(vinylpyrrolidone) hydrogels designed for nasal mucosal drug delivery.
Poly(vinylpyrrolidone) (PVP) hydrogels were crosslinked by gamma irradiation to add structure and rigidity, and then rheological and mucoadhesive properties were evaluated. The effects of PVP concentration, radiation dose, and additives, such as poly(ethylene glycol) (PEG) and glycerol, on rheological properties were investigated. In an oscillatory analysis, an increase in polymer concentrations increased the storage modulus (G') and the loss modulus (G″) but decreased the loss tangent (tan δ < 1). The relationships between G'or G″ and the frequency levelled off at higher frequencies, which is indicative of polymer chain entanglement and network formation. Each of the 6% PVP hydrogels exhibited plastic flow with rheopectic behavior. PVP concentration, radiation dose, and the presence of PEG or glycerol influenced the rheological and mucoadhesive properties of the hydrogels. However, adding acyclovir to the formulation did not have a profound effect on the rheological behavior of the hydrogels. The results suggest that a 3% PVP hydrogel with 1% PEG crosslinked with 20 kGy is the most appropriate hydrogel. The results demonstrated the successful complementary application of oscillatory and flow rheometry to characterize and develop a hydrogel for mucosal drug administration.


Month-by-month age analysis of the risk for serious bacterial infections in febrile infants with bronchiolitis.
This study's aim was to assess the risk of serious bacterial infections (SBI) in each of the first 3 months in hospitalizes febrile infants with bronchiolitis. The risk of SBI was compared between hospitalized infant with or without bronchiolitis by age in months. A total of 1125 febrile infants aged ≤3 months were admitted during the study period, 948 without and 177 with bronchiolitis. The incidence of SBI was significantly lower among infants with bronchiolitis compared with those without (4% vs 12.2%, P < .001). However, within the subgroup of neonates with bronchiolitis aged ≤28 days, the incidence of SBI was 9.7% and was not significantly lower than in neonates without bronchiolitis. The risk of SBI among febrile infants with bronchiolitis is significantly lower compared with febrile infants without bronchiolitis, but only after the neonatal period in which the risk for urinary tract infection was relatively high (9.7%).


The region essential for efficient autonomous replication of pSa in Escherichia coli.
Comparative analyses were made between plasmid pSa17, a deletion derivative of pSa that is capable of replicating efficiently in Escherichia coli and plasmid pSa3, a derivative that is defective for replication. By comparing the restriction maps of these two derivatives, the regions essential for replication and for stable maintenance of the plasmid were determined. A 2.5 kb DNA segment bearing the origin of DNA replication of pSa17 was sequenced. A 36 kDa RepA protein was encoded in the region essential for replication. Downstream of the RepA coding region was a characteristic sequence including six 17 bp direct repeats, the possible binding sites of RepA protein, followed by AT-rich and GC-rich sequences. Furthermore, an 8 bp incomplete copy of the 17 bp repeat was found in the promoter region of the repA gene. Based on the hypothesis that RepA protein binds to this partial sequence as well as to intact 17 bp sequences, an autoregulatory system for the synthesis of RepA protein may be operative. Another open reading frame (ORF) was found in the region required for the stability of the plasmid. The putative protein encoded in this ORF showed significant homology to several site-specific recombination proteins. A possible role of this putative protein in stable maintenance of the plasmid is discussed.


Cellular and chemical neuroscience of mammalian sleep.
Extraordinary strides have been made toward understanding the complexities and regulatory mechanisms of sleep over the past two decades thanks to the help of rapidly evolving technologies. At its most basic level, mammalian sleep is a restorative process of the brain and body. Beyond its primary restorative purpose, sleep is essential for a number of vital functions. Our primary research interest is to understand the cellular and molecular mechanisms underlying the regulation of sleep and its cognitive functions. Here I will reflect on our own research contributions to 50 years of extraordinary advances in the neurobiology of slow-wave sleep (SWS) and rapid eye movement (REM) sleep regulation. I conclude this review by suggesting some potential future directions to further our understanding of the neurobiology of sleep.


Strengthening midwifery education through clinical experience: Findings from a qualitative study in Indonesia.
One of the Indonesian Government's strategies to reduce maternal mortality rates has been to place a midwife in every village to provide midwifery care and facilitate essential primary healthcare services. To increase the numbers of midwives, the Indonesian Government began opening midwifery schools. However, Indonesia's maternal mortality rates remained high. This raises the question of the quality of midwifery education in Indonesia and how this education could be strengthened so that midwifery plays a key role in reducing maternal mortality rates. The aim of this study was to identify the barriers and enablers to strengthening midwifery education in Indonesia. A qualitative descriptive approach and in-depth interviews was the method used with 37 participants from 12 midwifery schools in eight cities situated in six provinces in Indonesia. Indonesian midwives, midwifery lecturers, midwifery students, newly graduated midwives, and obstetricians were interviewed in Bahasa Indonesia. Interviews were transcribed, translated, and thematically analysed following Braun and Clark (2006). This article focuses on findings on "midwifery clinical experience", a theme which contained four sub-themes: "effective hands-on clinical experience", "theory-practice gap", "role of the mentor in practice", and "the system in the clinical environment". This study highlights barriers to preparing midwifery students for obtaining adequate midwifery knowledge and skills during clinical placement. Quality clinical experience would improve knowledge and skills for better preparedness for students to competently meet their role as midwives, contributing to the strengthening of midwifery education in Indonesia.


A double-blind controlled trial of betamethasone dipropionate 0.05% (Diproderm) in comparison with fluocinolone acetonide 0.025% (Synalar) in psoriasis and other steroid-responsive dermatoses.
In a double-blind randomized study, sixty-two patients suffering from psoriasis or eczema were treated, twice daily for three weeks, either with 0.05% betamethasone 17, 21-dipropionate cream or with 0.025% fluocinolone acetonide cream. The results showed that both topical corticosteroid preparations were effective, well tolerated and cosmetically acceptable. Fifty-seven per cent of the patients treated with betamethasone dipropionate were rated as being 'much better' in the overall assessment of response at the end of the trial period compared to only 25% of those in the fluocinolone acetonide group.


Critical evaluation of the factorial and heart-rate recording methods for the determination of energy expenditure of free-living elderly people.
The aim of the present study was to validate against the doubly-labelled water (DLW) technique the factorial method and the heart rate (HR) recording method for determining daily energy expenditure (DEE) of elderly people in free-living conditions. The two methods were first calibrated and validated in twelve healthy subjects (six males and six females; 70.1 (SD 2.7) years) from open-circuit whole-body indirect calorimetry measurements during three consecutive days and during 1 d respectively. Mean energy costs of the various usual activities were determined for each subject using the factorial method, and individual relationships were set up between HR and energy expenditure for the HR recording method. In free-living conditions, DEE was determined over the same period of time by the DLW, the factorial and the HR recording methods during 17, 14 and 4 d respectively. Mean free-living DEE values for men estimated using the DLW, the factorial and the HR recording methods were 12.8 (SD 3.1), 12.7 (SD 2.2) and 13.5 (SD 2.7) MJ/d respectively. Mean free-living DEE values for women were 9.6 (SD 0.8), 8.8 (SD 1.2) and 10.2 (SD 1.5) MJ/d respectively. No significant differences were found between the three methods for either sex, using the Bland & Altman (1986) test. Mean differences in DEE of men were -0.9 (SD 11.8) % between the factorial and DLW methods, and + 4.7 (SD 16.1) % between the HR recording and DLW methods. Similarly, in women, mean differences were -7.7 (SD 12.7) % between the factorial and DLW methods, and + 5.9 (SD 8.8) % between the HR recording and DLW methods. It was concluded that the factorial and the HR recording methods are satisfactory alternatives to the DLW method when considering the mean DEE of a group of subjects. Furthermore, mean energy costs of activities calculated in the present study using the factorial method were shown to be suitable for determining free-living DEE of elderly people when the reference value (i.e. sleeping metabolic rate) is accurately measured.


Courier service for phosphatidylinositol: PITPs deliver on demand.
Phosphatidylinositol is the parent lipid for the synthesis of seven phosphorylated inositol lipids and each of them play specific roles in numerous processes including receptor-mediated signalling, actin cytoskeleton dynamics and membrane trafficking. PI synthesis is localised to the endoplasmic reticulum (ER) whilst its phosphorylated derivatives are found in other organelles where the lipid kinases also reside. Phosphorylation of PI to phosphatidylinositol (4,5) bisphosphate (PI(4,5)P2) at the plasma membrane and to phosphatidylinositol 4-phosphate (PI4P) at the Golgi are key events in lipid signalling and Golgi function respectively. Here we review a family of proteins, phosphatidylinositol transfer proteins (PITPs), that can mobilise PI from the ER to provide the substrate to the resident kinases for phosphorylation. Recent studies identify specific and overlapping functions for the three soluble PITPs (PITPα, PITPβ and PITPNC1) in phospholipase C signalling, neuronal function, membrane trafficking, viral replication and in cancer metastases.


The biology of the mesothelium during peritoneal dialysis.
Substantial derangements of mesothelial biology are observed during experimental simulations of dialysis conditions, inferred from the content of human dialysis effluent and visualized by microscopy of human mesothelial biopsies. Can osmotically active solutions be made biocompatible with the osmoregulatory system of the mesothelium? Can the contributions of the mesothelium to host defenses against inflammation and/or infection be supported during CAPD? Do underlying metabolic derangements present in various kidney diseases and end-stage renal disease, regardless of cause, require customized CAPD protocols and solutions? Use of dialysis solutions less directly toxic to the mesothelium is a necessary step toward some day manipulating peritoneal biology by pharmacological and therapeutic modalities.


Is influenza vaccination cost effective for healthy people between ages 65 and 74 years? A randomised controlled trial.
The aim of this study was to determine the cost effectiveness of influenza vaccination for healthy people aged 65-74 years living in the UK. People without risk factors for influenza (chronic heart, lung or renal disease, diabetic, immunosuppressed or those living in an institution) were identified from 20 general practitioner (GP) practices in Liverpool in September 1999. 729/5875 (12.4%) eligible individuals were recruited and randomised to receive either influenza vaccine or placebo (ratio 3:1), with all participants receiving 23-valent-pneumococcal polysaccharide vaccine unless already administered. The primary analysis was the frequency of influenza as recorded by a GP diagnosis of pneumonia or influenza like illness. In 2000, the UK vaccination policy was changed with influenza vaccine becoming available for all people aged 65 years and over irrespective of risk. As a consequence of this policy change, the study had to be fundamentally restructured and only results obtained over a one rather than the originally planned two-year randomised controlled trial framework were used. Results from 1999/2000 demonstrated no significant difference between groups for the primary outcome (relative risk 0.8, 95% CI 0.16-4.1). In addition, there were no deaths or hospitalisations for influenza associated respiratory illness in either group. The subsequent analysis, using both national and local sources of evidence, estimated the following cost effectiveness indicators: (1) incremental NHS cost per GP consultation avoided = 2000 pound sterling; (2) incremental NHS cost per hospital admission avoided = 61,000 pound sterling; (3) incremental NHS cost per death avoided = 1,900,000 pound sterling and (4) incremental NHS cost per QALY gained = 304,000 pound sterling. The analysis suggested that influenza vaccination in this population would not be cost effective.


Hollow N-doped bimetal carbon spheres with superior ORR catalytic performance for microbial fuel cells.
Herein, we report the fabrication of bimetal ZIF-derived Cu/Co/N co-doped hollow spheres as effective oxygen reduction reaction (ORR) catalysts by the pyrolysis of core-shell polystyrene@Cu/Co-ZIFs (PS@Cu/Co-ZIFs) composite precursors. As a thermally degradable template, PS spheres are a key to determine the catalyst size. The bimetal ZIF hollow spheres were synthesized via a simple carbonization reaction, where ZIFs shells formed on PS spheres after the addition of metal sources, (Co(NO3)2 and Cu(NO3)2), and organic ligand 2-methylimidazole. Benefiting from the hollow structural and abundant catalytic sites, the as-prepared Cu/Co/N-doped hollow spheres showed superior electrocatalytic performances and excellent durability than commercial Pt/C catalysts. The on-set and half-wave potentials of the Cu/Co/N-HS-3 catalyst were 0.25 and 0.13 V (vs Ag/AgCl), respectively, which were greater than those of 20% Pt/C catalysts (0.24 and 0.12 V). Moreover, the Cu/Co/N-HS-3 catalyst-based air-cathode microbial fuel cells (MFCs) exhibited maximum output voltage and power density of 620 mV and 1016 mW/m2, respectively, demonstrating superiority to commercial Pt/C catalyst-based MFCs (586 mV and 908 mW/m2).


Purification and characterization of native human insulin-like growth factor binding protein-6.
Insulin-like growth factor binding proteins (IGFBPs) are key regulators of insulin-like growth factor (IGF) mediated signal transduction and thereby can profoundly influence cellular phenotypes and cell fate. Whereas IGFBPs are extracellular proteins, intracellular activities were described for several IGFBP family members, such as IGFBP-3, which can be reinternalized by endocytosis and reaches the nucleus through routes that remain to be fully established. Within the family of IGFBPs, IGFBP-6 is unique for its specific binding to IGF-II. IGFBP-6 was described to possess additional IGF-independent activities, which have in part been attributed to its translocation to the nucleus; however, cellular uptake of IGFBP-6 was not described. To further explore IGFBP-6 functions, we developed a new method for the purification of native human IGFBP-6 from cell culture supernatants, involving a four-step affinity purification procedure, which yields highly enriched IGFBP-6. Whereas protein purified in this way retained the capacity to interact with IGF-II and modulate IGF-dependent signal transduction, our data suggest that, unlike IGFBP-3, human IGFBP-6 is not readily internalized by human tumor cells. To summarize, this work describes a novel and efficient method for the purification of native human insulin-like growth factor binding protein 6 (IGFBP-6) from human cell culture supernatants, applying a four-step chromatography procedure. Intactness of purified IGFBP-6 was confirmed by IGF ligand Western blot and ability to modulate IGF-dependent signal transduction. Cellular uptake studies were performed to further characterize the purified protein, showing no short-term uptake of IGFBP-6, in contrast to IGFBP-3.


Bactericidal activity of the combinations of gentamicin with clindamycin or chloramphenicol against species of Escherichia coli and Bacteroides fragilis.
The bactericidal activity of clindamycin, chloramphenicol, and gentamicin alone and of gentamicin plus clindamycin and gentamicin plus chloramphenicol was studied on 8 strains of Escherichia coli and 10 strains of Bacteroides fragilis isolated from clinical material. Gentamicin did not interfere with the activity of clindamycin or chloramphenicol against B. fragilis. The activity of gentamicin against E. coli was not influenced by clindamycin, but chloramphenicol suppressed the rapid bactericidal activity of gentamicin in seven out of eight strains of E. coli examined.


Effect of pituitary gonadotrophins on proliferation of primary cultures of human ovarian stroma.
Proliferation of ovarian stromal cells is a common phenomenon in peri- and post-menopausal ovaries. It is generally assumed to be secondary to the rise in circulating gonadotrophins at the menopause, though the process by which it occurs is poorly understood. This study aimed to examine the effect of menopausal levels of pituitary gonadotrophins on the growth of primary cultures of ovarian stroma. A culture system was developed using primary explants of ovarian stroma on a collagen substrate. The effect of follicle stimulating hormone (FSH; 10(-5) g/l) and luteinizing hormone (LH; 10(-5) g/l) on the proliferation of cultures derived from the cortices and medullae of ten ovaries was evaluated using a dual radiothymidine labelling technique. FSH was stimulatory to cortical cultures from 9/10 ovaries and medullary cultures from 7/10 ovaries, while LH was stimulatory to cortical cultures from 6/9 ovaries and medullary cultures from 5/10 ovaries. The responsiveness of the cultures did not correlate with the degree of hyperplasia in vivo. This study demonstrates that pituitary gonadotrophins may modulate the growth of stromal cells in culture, and thus may play a role in the process whereby stromal proliferation occurs in peri- and post-menopausal ovaries.


Automated cross-sectional analysis of trained, severely atrophied, and recovering rat skeletal muscles using MyoVision 2.0.
The number of myonuclei within a muscle fiber is an important factor in muscle growth, but its regulation during muscle adaptation is not well understood. We aimed to elucidate the time course of myonuclear dynamics during endurance training, loaded and concentric resistance training, and nerve silencing-induced disuse atrophy with subsequent recovery. We modified tibialis anterior muscle activity in free-living rats with electrical stimulation from implantable pulse generators, or with implantable osmotic pumps delivering tetrodotoxin (TTX) to silence the motor nerve without transection. We used the updated, automated software MyoVision to measure fiber-type-specific responses in whole tibialis anterior cross sections (∼8,000 fibers each). Seven days of continuous low-frequency stimulation (CLFS) reduced muscle mass (-12%), increased slower myosin isoforms and reduced IIX/IIB fibers (-32%), and substantially increased myonuclei especially in IIX/IIB fibers (55.5%). High-load resistance training (spillover) produced greater hypertrophy (∼16%) in muscle mass and fiber cross-sectional area (CSA) than low-load resistance training (concentric, ∼6%) and was associated with myonuclear addition in all fiber types (35%-46%). TTX-induced nerve silencing resulted in progressive loss in muscle mass, fiber CSA, and myonuclei per fiber cross section (-50.7%, -53.7%, and -40.7%, respectively, at 14 days). Myonuclear loss occurred in a fiber-type-independent manner, but subsequent recovery during voluntary habitual activity suggested that type IIX/IIB fibers contained more new myonuclei during recovery from severe atrophy. This study demonstrates the power and accuracy provided by the updated MyoVision software and introduces new models for studying myonuclear dynamics in training, detraining, retraining, repeated disuse, and recovery.NEW & NOTEWORTHY We introduce new models for studying fiber-type-specific myonuclear dynamics in muscle training, detraining, retraining, disuse, and recovery. We show that the various fiber types do not respond identically and that myonuclear number changes during adaptation. We also critically assess an updated version of MyoVision automated image analysis software to quantify whole muscle immunofluorescent microscopical images in a faster and less computer intensive manner. MyoVision remains open source and freely available with more user-controlled features.


Inherited electrophoretic hemoglobin patterns among 20 inbred strains of mice.
The hemoglobin from mice of six inbred strains is of the single-spot electrophoretic type, and that from 14 inbred strains is of the diffuse type. No selective advantage is apparent for either type. The distribution among strains shows some relation to the history of the development of the strains.


Role of HSP70 in cytoplasm protection against thermal stress in rohu, Labeo rohita.
To understand the function of HSP70 of Labeo rohita (LrHSP70) in cellular protection, LrHSP70 ORF cDNA was inserted into the plasmid of pET-32a(+) or pEGFP-L1. Then, the recombinant plasmids were transformed or transfected into Escherichia coli cells, mouse myeloma cells (MPC-11) or fish hepatoma cells (PLHC-1). Western blot results revealed that LrHSP70 was expressed in E. coli cells and molecular weight was estimated to be 70 kDa. In cells, LrHSP70 was over-expressed following thermal or cold stress. Results revealed that LrHSP70 protected prokaryotic cells against thermal or cold extremes as well as played the same role in MPC-11 and PLHC-1 cells. After heat treatment at 42 °C for 1 h, the viability of the cell was declined considerably. PLHC-1 cells with pEGFP-L1/LrHSP70 exhibited a higher survival rate (50%) than wild-type cells (18%) or cells with only pEGFP-L1 (21.2%). When the time lag extended to 2 h, the survival rates were 30%, 3.4% and 5.3% respectively. The present study revealed that LrHSP70 plays an important role in response to thermal and cold stress in fish.


Osteobiology, strain, and microgravity. Part II: studies at the tissue level.
Loading microgravity, and/or defective mechanical strain-forces have important effects on bone cells and bone quality and quantity. The complex mechanisms induced by strain and microgravity on bone cells have been reviewed in Part I of this paper. In Part II, we have considered the data on the alterations induced by unloading and microgravity on the skeleton and the mechanisms that are involved at the tissue level in animals and humans.


Secondary loss and pain-associated disability: theoretical overview and treatment implications.
In the area of occupational pain disability, a major barrier to effective rehabilitation of patients may be the extensive personal losses that can arise as secondary features of chronic pain disability. In this review, we discuss the concept of secondary loss and how it can have a profound impact on patients with occupational pain disability. Such secondary loss issues are extremely important to consider in any rehabilitation program in order to ensure the most comprehensive and compassionate treatment of these patients. We discuss the types of intervention that may be employed within the context of interdisciplinary rehabilitation programs.


Sakacin M, a bacteriocin-like substance from Lactobacillus sake 148.
The antagonistic activity of Lactobacillus sake 148 was evaluated during its growth on complex broth media and in a semisynthetic defined medium (SDM) with various supplements. The antagonistic activity was a growth-associated property, being detected and quantified when L. sake 148 was grown at either 4, 8, 16, 25 or 32 degrees C. The concentrated culture supernatant of L. sake 148 was subjected to purification by lyophilization and gel filtration. The purification procedure resulted in a small increase in its specific activity (7-fold) and in a low recovery of the original inhibitory activity (8%). Gel filtration analysis of the partially purified activity on Sephadex G-50 revealed an apparent molecular weight of 4640. The partially purified antagonistic activity of L. sake 148 was destroyed by treatment with proteolytic enzymes. However, the antagonistic activity was resistant to heat, having D-values at 121, 135 and 150 degrees C of 23.8, 17.4 and 15.2 min, respectively.


Activational effects of sex hormones on cognition in men.
Changing world demographic patterns, such as the increasing number of older people and the growing prevalence of cognitive impairment, present serious obstacles to preserving the quality of life and productivity of individuals. The severity of dementia varies from subclinical, mild cognitive impairment to neurodegenerative diseases such as Alzheimer's. In normally ageing men, these age-related cognitive declines are accompanied by gradual but marked decreases in androgen levels and changes in other hormone profiles. While developmental effects of sex hormones on cognition in the pre- and early postnatal period have been demonstrated, their activational effects in later life are still a focus of contemporary research. Although there is a plethora of published research on the topic, results have been inconsistent with different studies reporting positive, negative or no effects of sex hormones on various aspects of mental agility. This review summarizes the evidence supporting the biological plausibility of the activational effects of sex hormones upon cognition and describes the mechanisms of their actions. It offers a comprehensive summary of the studies of the effects of sex hormones on fluid intelligence in men utilizing elements from the Cochrane Collaboration Guidelines for Reviews. The results of both observational (cross-sectional and longitudinal) and interventional studies published to date are collated in table form and further discussed in the text. Factors contributing to the difficulties in understanding the effects of sex hormones on cognition are also examined. Although there is convincing evidence that steroid sex hormones play an organizational role in brain development in men, the evidence for activational effects of sex hormones affecting cognition in healthy men throughout adult life remains inconsistent. To address this issue, a new multifactorial approach is proposed which takes into account the status of other elements of the sex hormones axis including receptors, enzymes and other hormones.


Multielectrode Arrays for Functional Phenotyping of Neurons from Induced Pluripotent Stem Cell Models of Neurodevelopmental Disorders.
In vitro multielectrode array (MEA) systems are increasingly used as higher-throughput platforms for functional phenotyping studies of neurons in induced pluripotent stem cell (iPSC) disease models. While MEA systems generate large amounts of spatiotemporal activity data from networks of iPSC-derived neurons, the downstream analysis and interpretation of such high-dimensional data often pose a significant challenge to researchers. In this review, we examine how MEA technology is currently deployed in iPSC modeling studies of neurodevelopmental disorders. We first highlight the strengths of in vitro MEA technology by reviewing the history of its development and the original scientific questions MEAs were intended to answer. Methods of generating patient iPSC-derived neurons and astrocytes for MEA co-cultures are summarized. We then discuss challenges associated with MEA data analysis in a disease modeling context, and present novel computational methods used to better interpret network phenotyping data. We end by suggesting best practices for presenting MEA data in research publications, and propose that the creation of a public MEA data repository to enable collaborative data sharing would be of great benefit to the iPSC disease modeling community.


Time course of right ventricular functional parameters after surgical correction of tetralogy of Fallot determined by cardiac magnetic resonance.
To evaluate changes of right ventricular (RV) parameters in follow-up examinations after corrected tetralogy of Fallot (TOF) by cardiac magnetic resonance (CMR). CMR was performed twice within 4 years in 45 patients using a 1.5 T scanner. RV-volumes and pulmonary-regurgitant-fractions (PRF) were calculated from standard cine-sequences and flow-sensitive gradient-echo images, respectively. Patients were divided into two groups depending on the post-operative (po) interval (group 1 ≤5 years po; group 2 >5 years po) and subgroups depending on type of surgery (transannular vs. non-transannular). Patient groups were compared among each other and differences between 1st and 2nd CMR were assessed. Furthermore, patients were compared with 25 healthy volunteers. Compared with controls RV-size was increased (group 1: p = 0.007; group 2: p < 0.001) and RV function decreased (group 1: p = 0.02; group 2: p < 0.001) in po TOF-patients. PRF was higher in group 2 compared with group 1 (p = 0.04) and significant changes of PRF between 1st and 2nd CMR were found in group 2 (p < 0.01), but not in group 1 (p = 0.29). Compared with the non-transannular subgroup, PRF (p < 0.001) and RV end-diastolic-volume index (RV-EDVI) (p = 0.03) were significantly higher in patients with a transannular patch, EDVI increased between 1st and 2nd CMR. After correction, no significant changes of RV myocardial mass index (RV-MMI) were found. After correction of TOF, RV-size, RV-muscle mass (RV-MM) was increased and ejection fraction decreased in "early" follow-up already. Whereas these parameters can remain stable over a long time period, the PRF significantly increased in "late" follow-up dependent on the po interval. Overall, transannular patching went along with higher PRF and bigger RV-size as well as a greater dynamic of these parameters in the time course, which makes this subgroup highly in need of regular follow-up examinations for the optimal timing of re-interventions. In contrast, the increased RV-MM demonstrated no regression po.


Clinical hypothermia temperatures increase complement activation and cell destruction via the classical pathway.
Therapeutic hypothermia is a treatment modality that is increasingly used to improve clinical neurological outcomes for ischemia-reperfusion injury-mediated diseases. Antibody-initiated classical complement pathway activation has been shown to contribute to ischemia-reperfusion injury in multiple disease processes. However, how therapeutic hypothermia affects complement activation is unknown. Our goal was to measure the independent effect of temperature on complement activation, and more specifically, examine the relationship between clinical hypothermia temperatures (31-33°C), and complement activation. Antibody-sensitized erythrocytes were used to assay complement activation at temperatures ranging from 0-41°C. Individual complement pathway components were assayed by ELISA, Western blot, and quantitative dot blot. Peptide Inhibitor of complement C1 (PIC1) was used to specifically inhibit activation of C1. Antibody-initiated complement activation resulting in eukaryotic cell lysis was increased by 2-fold at 31°C compared with 37°C. Antibody-initiated complement activation in human serum increased as temperature decreased from 37°C until dramatically decreasing at 13°C. Quantitation of individual complement components showed significantly increased activation of C4, C3, and C5 at clinical hypothermia temperatures. In contrast, C1s activation by heat-aggregated IgG decreased at therapeutic hypothermia temperatures consistent with decreased enzymatic activity at lower temperatures. However, C1q binding to antibody-coated erythrocytes increased at lower temperatures, suggesting that increased classical complement pathway activation is mediated by increased C1 binding at therapeutic hypothermia temperatures. PIC1 inhibited hypothermia-enhanced complement-mediated cell lysis at 31°C by up to 60% (P = 0.001) in a dose dependent manner. In summary, therapeutic hypothermia temperatures increased antibody-initiated complement activation and eukaryotic cell destruction suggesting that the benefits of therapeutic hypothermia may be mediated via other mechanisms. Antibody-initiated complement activation has been shown to contribute to ischemia-reperfusion injury in several animal models, suggesting that for diseases with this mechanism hypothermia-enhanced complement activation may partially attenuate the benefits of therapeutic hypothermia.


Four decades of speech-language pathology in India: changing perspectives and challenges of the future.
The paper traces the evolution and current status of speech-language pathology in India in its clinical and training aspects.


CT demonstration of a giant colonic diverticulum.
A case of giant sigmoid colonic diverticulum (GCD) is presented in which plain films showed an unchanging persistent large gas collection that did not opacify on barium enema. The computed tomographic scan revealed the GCD in close apposition to the adjacent sigmoid diverticulosis. Its walls were thin and more irregular than noted on plain films, and there was a suggestion of intraluminal contrast within it.


Pets in peril: The relative susceptibility of cats and dogs to procoagulant snake venoms.
Snakebite is a common occurrence for pet cats and dogs worldwide and can be fatal. In Australia the eastern brown snake (Pseudonaja textilis) is responsible for an estimated 76% of reported snakebite cases to domestic pets nationally each year, with the primary pathology being venom-induced consumptive coagulopathy. While only 31% of dogs survive P. textilis bites without antivenom, cats are twice as likely to survive bites (66%). Even with antivenom treatment, cats have a significantly higher survival rate. The reason behind this disparity is unclear. Using a coagulation analyser (Stago STA R Max), we tested the relative procoagulant effects of P. textilis venom-as well as 10 additional procoagulant venoms found around the world-on cat and dog plasma in vitro, as well as on human plasma for comparison. All venoms acted faster upon dog plasma than cat or human, indicating that dogs would likely enter coagulopathic states sooner, and are thus more vulnerable to procoagulant snake venoms. The spontaneous clotting time (recalcified plasma with no venom added) was also substantially faster in dogs than in cats, suggesting that the naturally faster clotting blood of dogs predisposes them to being more vulnerable to procoagulant snake venoms. This is consistent with clinical records showing more rapid onset of symptoms and lethal effects in dogs than cats. Several behavioural differences between cats and dogs are also highly likely to disproportionately negatively affect prognosis in dogs. Thus, compared to cats, dogs require earlier snakebite first-aid and antivenom to prevent the onset of lethal venom effects.


Live-cell imaging of glucose-induced metabolic coupling of β and α cell metabolism in health and type 2 diabetes.
Type 2 diabetes is characterized by β and α cell dysfunction. We used phasor-FLIM (Fluorescence Lifetime Imaging Microscopy) to monitor oxidative phosphorylation and glycolysis in living islet cells before and after glucose stimulation. In healthy cells, glucose enhanced oxidative phosphorylation in β cells and suppressed oxidative phosphorylation in α cells. In Type 2 diabetes, glucose increased glycolysis in β cells, and only partially suppressed oxidative phosphorylation in α cells. FLIM uncovers key perturbations in glucose induced metabolism in living islet cells and provides a sensitive tool for drug discovery in diabetes.


Ritter-type reaction of C-(1-bromo-1-deoxy-D-glycopyranosyl)formamides and its application for the synthesis of oligopeptides incorporating anomeric α-amino acids.
O-Peracetylated or -perbenzoylated C-(1-bromo-1-deoxy-D-glycopyranosyl)formamides of D-gluco, D-galacto, and D-arabino configuration were reacted with Ag(I)-salts or HgO in nitrile solvents to give N-acyl-1-cyano-D-glycopyranosylamines with an axial C-N bond at the anomeric centre. In the presence of HgBr(2), Hg(CN)(2), or InCl(3) the anomer of the above glycosylamine with an equatorial C-N bond was also isolated or detected. In CH(3)NO(2) solutions as few as 5-10 equiv of the nitrile were sufficient to get acceptable yields for the products. Under similar conditions N-substituted C-(2,3,4,6-tetra-O-acetyl-1-bromo-1-deoxy-β-D-galactopyranosyl)formamides gave anomeric spiro-oxazoline derivatives which, upon mild acidic hydrolysis, opened up to di- and tripeptides of anomeric α-amino acids.


Scar channels in cardiac magnetic resonance to predict appropriate therapies in primary prevention.
Scar characteristics analyzed by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related with ventricular arrhythmias. Current guidelines are based only on the left ventricular ejection fraction to recommend an implantable cardioverter-defibrillator (ICD) in primary prevention. Our study aims to analyze the role of imaging to stratify arrhythmogenic risk in patients with ICD for primary prevention. From 2006 to 2017, we included 200 patients with LGE-CMR before ICD implantation for primary prevention. The scar, border zone, core, and conducting channels (CCs) were automatically measured by a dedicated software. The mean age was 60.9 ± 10.9 years; 81.5% (163) were men; 52% (104) had ischemic cardiomyopathy. The mean left ventricular ejection fraction was 29% ± 10.1%. After a follow-up of 4.6 ± 2 years, 46 patients (22%) reached the primary end point (appropriate ICD therapy). Scar mass (36.2 ± 19 g vs 21.7 ± 10 g; P < .001), border zone mass (26.4 ± 12.5 g vs 16.0 ± 9.5 g; P < .001), core mass (9.9 ± 8.6 g vs 5.5 ± 5.7 g; P < .001), and CC mass (3.0 ± 2.6 g vs 1.6 ± 2.3 g; P < .001) were associated with appropriate therapies. Scar mass > 10 g (25.31% vs 5.26%; hazard ratio 4.74; P = .034) and the presence of CCs (34.75% vs 8.93%; hazard ratio 4.07; P = .003) were also strongly associated with the primary end point. However, patients without channels and with scar mass < 10 g had a very low rate of appropriate therapies (2.8%). Scar characteristics analyzed by LGE-CMR are strong predictors of appropriate therapies in patients with ICD in primary prevention. The absence of channels and scar mass < 10 g can identify patients at a very low risk of ventricular arrhythmias in this population.


Reversible his-tagged enzyme immobilization on functionalized carbon nanotubes as nanoscale biocatalyst.
Common enzyme immobilization methods on nanomaterials (adsorption, covalent binding, crosslinking, encapsulation) often generate problems in enzyme leaching, 3D structure change and diffusion resistance. We show here a detailed site-specific enzyme immobilization method that overcomes the foresaid limitations. It is based on the specific interaction between His-tagged enzyme and single-walled carbon nanotubes modified with N (α) ,N (α)-bis(carboxymethyl)-L: -lysine hydrate. This method does not require enzyme purification and the resulting nanoscale biocatalyst can maintain high enzyme activity and stability. The enzyme-loading capacity is also comparable with the reported immobilization capacity on carbon nanotubes by either covalent binding or adsorption. Furthermore, the immobilization is reversible for several cycles while maintaining high enzyme activity and the nanoscale biocatalyst can be regenerated easily.


Stock market reactions to COVID-19 lockdown: A global analysis.
The COVID-19 pandemic has caused dramatic changes in the way people around the globe live, and has had a profound negative impact on the global economy. Much of this negative impact did not result from the disease itself, but from the lockdown restrictions imposed to contain the spread of the virus. We investigate how national stock market indices reacted to the news of national lockdown restrictions in the period from January to May 2020. We find that lockdown restrictions led to different reactions in our sample of OECD and BRICS countries: there was a general negative effect resulting from the increase in lockdown restrictions, but we find strong evidence for underreaction during the lockdown announcement, followed by some overreaction that is corrected subsequently. This under-/overreaction pattern, however, is observed mostly during the first half of our time series, pointing to learning effects. Relaxation of the lockdown restrictions, on the other hand, had a positive effect on markets only during the second half of our sample, while for the first half of the sample, the effect is negative.


Adrenomedullin, amylin, calcitonin gene-related peptide and their fragments are potent inhibitors of gastric acid secretion in rats.
Adrenomedullin, amylin and calcitonin gene-related peptides (CGRP) share close sequence homology and have overlapping spectra of biological activities, particularly with respect to cardiovascular and gastrointestinal functions. Comparisons of the effects of these three peptides on gastric acid release have been made by i.v. infusions in conscious rats equipped with gastric fistulae. All peptides were extremely potent inhibitors of basal, pentagastrin- and 2-deoxy-D-glucose-stimulated gastric acid secretion with IC50 values in the subnanomolar to nanomolar range. These effects were not inhibited by C-terminal extra-cyclic fragments of the peptides which often act as competitive receptor antagonists in other biological systems. At high concentrations C-terminal fragments of human adrenomedullin and rat alpha-calcitonin gene-related peptide displayed some receptor agonist activity. Furthermore, the N-terminally situated disulfide-bridged ring fragments, human adrenomedullin-(15-22), rat amylin-(1-8) and rat alpha-calcitonin gene-related peptide-(1-8), retained significant gastric acid inhibitory potencies thus suggesting involvement of receptor(s) with significantly differing ligand binding profiles than those characterized previously.


Growth differentiation factor 15 in patients with congenital dyserythropoietic anaemia (CDA) type II.
Congenital dyserythropoietic anaemias (CDAs) are heterogeneous, hereditary disorders hallmarked by ineffective erythropoiesis and tissue iron overload. Growth differentiation factor 15 (GDF15) was suggested to mediate iron overload in iron-loading anaemias, such as the thalassaemias and CDAI by suppressing hepcidin, the key regulator of iron absorption. Here, we show that serum GDF15 concentrations are elevated in subjects with CDAI and CDAII. Despite similar disease characteristics, CDAI patients present with significantly higher GDF15 concentrations compared to CDAII patients. Hepcidin concentrations are inappropriately low in CDAII patients considering the severe hepatic iron overload associated with this disorder. GDF15 significantly correlates with the degree of anaemia (Hb), the response of erythropoiesis (reticulocyte index) as well as with iron availability in the serum (transferrin saturation). The observation that GDF15 is elevated in CDAII patients is consistent with the proposal that GDF15 is among the erythroid factors down-regulating hepcidin and contributing to iron overload in conditions of dyserythropoiesis.


The National Institute for Health and Clinical Excellence and its role in assessing the value of new cancer treatments in England and Wales.
The boundaries of medical science in the treatment of cancer are constantly extending. Developments of existing treatments, innovative approaches, new discoveries, and more targeted therapeutic options are translating into practice. With advances come increasing costs, often of a magnitude that stretches finite financial resources. When decisions about funding are made on behalf of a population, standardized processes and methods are needed in order to produce robust guidance in a fair, consistent, and transparent way. The challenges of making these difficult decisions are brought into particularly stark relief when potentially life-extending treatments for patients with a short life expectancy are appraised. The National Institute for Health and Clinical Excellence (NICE) produces guidance on the clinical- and cost-effectiveness of medicines compared with current standard practice. Approximately 40% of the technologies appraised by NICE are indicated for cancer, and the majority of these are pharmaceuticals, mostly biological agents. This article provides an overview of the current role of NICE in making new technologies for cancer available in England and Wales. This includes a summary of experiences with end-of-life treatments and the supplementary advice regarding such treatments that was issued by NICE to its decision-making committees in 2009.


Predictors of neurologically favorable survival among patients with out-of-hospital cardiac arrest: A tertiary referral hospital experience.
Despite recent advances in medical support and interventions, only 5% to 10% of patients with out-of-hospital cardiac arrest (OHCA) survive to discharge. In this study, factors related to neurologically favorable survival in patients with OHCA were analyzed. A total of 129 patients who were admitted to hospital with OHCA were retrospectively enrolled. Sustained return of spontaneous circulation (ROSC) (ROSC lasting >20 min) was achieved in 29 (22.4%) patients. Percentage of cardiac arrests with ischemic etiology was significantly higher in successful ROSC group (p<0.001). In multivariate logistic regression analysis, cardiac arrest with ischemic etiology (p=0.004) and cardiopulmonary resuscitation (CPR) duration (p=0.013) were found to be independent predictors for ROSC. One-minute increment in CPR duration was associated with 1.202-fold increase in failure to achieve ROSC. Among patients with ROSC, 7 (5.4%) survived to hospital discharge, and 1-minute increment in CPR duration was associated with a 1.123-fold decrease in neurologically favorable survival (p=0.005). In patients with OHCA, ischemic etiology is associated with better ROSC rate compared to other reasons for cardiac arrest, and patients with prolonged CPR are less likely to survive.


Implications for the use of postural analysis as a clinical diagnostic tool: reliability of quantifying upright standing spinal postures from photographic images.
A repeated measures design was used to test the reliability of standing spine postures within subjects using a biologically relevant measure determined by digitization of images and to compare the results to a previously tested vertical reference method. Twenty subjects attended 3 sessions consisting of 5 trials each. Photographs of the sagittal and posterior views of normal upright standing were taken. Landmarks were digitized and cervical, thoracic, and lumbar spinal angles were calculated using the algebraic dot product. Intraclass correlation coefficients were used to evaluate intrasubject reliability across sessions. According to the intraclass correlation coefficients, posture had good to excellent reliability in the sagittal view and provided a more stable measure of spinal angles than the posterior view. Mean repositioning errors were less than 6 degrees and 2 degrees in the sagittal and posterior views, respectively. Although the repeatability of posture was improved in the sagittal view, when a biological measure was used instead of an external vertical reference to calculate spinal angles, individual subject posture was still variable. This brings into question the effectiveness and validity of using surface skin markers to track postural changes due to clinical interventions. If the postural analysis approach is to be used to detect changes due to clinical treatment, such changes must be larger than the baseline repositioning errors seen in healthy subjects.


The toxicity of benomyl, thiophanate-methyl, and BCM to four freshwater organisms.
The EC50 or LC50 values after a 2-day exposure of the three fungicides benomyl, thiophanate-methyl and BCM, have been determined using four freshwater organisms: Chlorella pyrenoidosa, Daphnia magna, Lebistes reticulatus and Salmo gairdneri. The influence of BCM on the reproductive capacity of Daphnia was also investigated and from these data provisional ecological limit was established.


LIFETIME REPRODUCTIVE SUCCESS, SELECTION, AND THE OPPORTUNITY FOR SELECTION IN THE WHITE-TAILED SKIMMER PLATHEMIS LYDIA (ODONATA: LIBELLULIDAE).
We present estimates of lifetime reproductive success in Plathemis lydia, a territorial dragonfly. We partition the opportunity for selection into multiplicative episodes using the techniques of Arnold and Wade (1984a, 1984b) and measure selection on several morphological and behavioral characters. For both sexes, variance in survivorship was the largest contribution to variance in lifetime reproductive success. Covariance effects are also strong for both sexes, suggesting considerable non-independence of episodes. Opportunity for selection calculated on a daily basis did not approximate analogous values determined from lifetime reproductive success. Phenotypic characters for which we investigated selection included body mass, hind wing length, first date of reproduction, and (for males) an index of territorial aggressiveness. We failed to find any significant direct targets of selection in either males or females. However, the combined effects of direct and indirect selection on early reproduction were significant for males, acting primarily through increased survivorship and increased time per day spent at the pond. Similarly, females present earlier in the season had shorter interclutch intervals. Partitioning of selection acting on male hind wing length and on aggressiveness reveals relationships between selective episodes, possibly indicative of phenotypic trade-offs between natural and sexual selection through male-male competition for females. Division of selection into episodes is a useful technique for identifying the source of selection. However, ordering effects can bias results, except when episodes occur in strictly chronological sequence. We present a method for circumventing this difficulty.


Transfer-RNA, an early gene?
The theory of self-reproductive molecular systems involves the consequence that translation must have started from a selected distribution of RNA molecules, that comprised GC-rich sequences of a length less than 100 nucleotides. This implies a joint function of messenger and adaptor, which both had to be recruited from the same mutant distribution. The reconstruction of tRNA precursors yields such a molecule showing some reverberation of a codon pattern GNC. These findings suggest that tRNA has been the earliest component of the translation machinery.


Murid herpesvirus-4 lacking thymidine kinase reveals route-dependent requirements for host colonization.
Gammaherpesviruses infect at least 90 % of the world's population. Infection control is difficult, in part because some fundamental features of host colonization remain unknown, for example whether normal latency establishment requires viral lytic functions. Since human gammaherpesviruses have narrow species tropisms, answering such questions requires animal models. Murid herpesvirus-4 (MuHV-4) provides one of the most tractable. MuHV-4 genomes delivered to the lung or peritoneum persist without lytic replication. However, they fail to disseminate systemically, suggesting that the outcome is inoculation route-dependent. After upper respiratory tract inoculation, MuHV-4 infects mice without involving the lungs or peritoneum. We examined whether host entry by this less invasive route requires the viral thymidine kinase (TK), a gene classically essential for lytic replication in terminally differentiated cells. MuHV-4 TK knockouts delivered to the lung or peritoneum were attenuated but still reached lymphoid tissue. In contrast, TK knockouts delivered to the upper respiratory tract largely failed to establish a detectable infection. Therefore TK, and by implication lytic replication, is required for MuHV-4 to establish a significant infection by a non-invasive route.


Glial role in oxaliplatin-induced neuropathic pain.
Oxaliplatin, a platinum-based chemotherapeutic agent, has become a standard treatment for advanced colorectal cancer. The dose-limiting toxicity of this compound is the development of peripheral neuropathy. A tangled panel of symptoms, sensory loss, paresthesia, dysesthesia and pain, may be disabling for patients and adversely affect their quality of life. Recently, we described a characteristic glial activation profile in a rat model of oxaliplatin-induced neuropathy. Glial cells are considered a new pharmacological target for neuropathic pain relief but its relevance in chemotherapy-dependent neuropathies is debated. Aimed to evaluate the significance of glial activation in pain generated by oxaliplatin, the microglial inhibitor minocycline or the astrocyte inhibitor fluorocitrate were continuously infused by intrathecal route in oxaliplatin-treated rats. Both compounds significantly reduced oxaliplatin-evoked pain though the efficacy of fluorocitrate was higher revealing a prominent role of astrocytes. Immunohistochemical analysis of the dorsal horn confirmed the specific Iba1-positive cell inhibition caused by minocycline as well as the selectivity of fluorocitrate on GFAP-positive cells. The activation of astrocytes in minocycline-treated rats suggests a microglia-independent modulation of astrocytes by oxaliplatin neurotoxicity. Neither the selective activation of astrocyte after minocycline treatment nor the exclusive microglial response after fluorocitrate is able to evoke pain. Morphometric and morphological determinations performed on dorsal root ganglia evidenced that the glial inhibitors did not prevent the oxaliplatin-dependent increase of eccentric nucleoli and multinucleolated neurons. The decrease of soma area was also unaltered. In summary, these data highlight the role of central glial cells in oxaliplatin-dependent neuropathic pain. On the other hand, glial inhibition is not associated with neuroprotective effects suggesting the need for careful modulation of glial signaling to prevent the pathophysiology that leads to persistent neuropathic pain.


Repurposing of HIV/HCV protease inhibitors against SARS-CoV-2 3CLpro.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen that caused the global COVID-19 outbreak. The 3C-like protease (3CLpro) of SARS-CoV-2 plays a key role in virus replication and has become an ideal target for antiviral drug design. In this work, we have employed bioluminescence resonance energy transfer (BRET) technology to establish a cell-based assay for screening inhibitors against SARS-CoV-2 3CLpro, and then applied the assay to screen a collection of known HIV/HCV protease inhibitors. Our results showed that the assay is capable of quantification of the cleavage efficiency of 3CLpro with good reproducibility (Z' factor is 0.59). Using the assay, we found that 9 of 26 protease inhibitors effectively inhibited the activity of SARS-CoV-2 3CLpro in a dose-dependent manner. Among them, four compounds exhibited the ability to bind to 3CLproin vitro. HCV protease inhibitor simeprevir showed the most potency against 3CLpro with an EC50 vale of 2.6 μM, bound to the active site pocket of 3CLpro in a predicted model, and importantly, exhibited a similar activity against the protease containing the mutations P132H in Omicron variants. Taken together, this work demonstrates the feasibility of using the cell-based BRET assay for screening 3CLpro inhibitors and supports the potential of simeprevir for the development of 3CLpro inhibitors.


8;20 chromosomal translocation in a case of acute leukemia. Cytogenetic, immunophenotypic, ultrastructural, and molecular characteristics.
An 8;20 chromosomal translocation was observed in the leukemia cells of a 3-year-old girl. To our knowledge, this is the first report of this translocation in de novo acute leukemia. This chromosomal defect was present in the leukemia cells at diagnosis and also at relapse, but remission bone marrow cells had the 46,XX karyotype. By morphologic and cytochemical criteria the leukemia was myeloid but these features were more lymphoid when the leukemia recurred. However, the immunophenotype was consistent with myeloid leukemia and did not change at relapse. No evidence for either immunoglobulin or TCR gene rearrangement was observed.


Discussion of parameter estimation in biological modelling: Algorithms for estimation and evaluation of the estimates.
This paper is concerned with the estimation of parameters when mathematical models are fitted to data. Two new algorithms are presented. The first is fast (economical in computation time), requires no initial estimates, but is not so accurate. The second requires more computation time, and fairly accurate initial estimates, but achieves high accuracy. The models discussed consist of sets of coupled, non-linear differential equations, but the second algorithm is applicable to wider classes of models as well.The accuracy of the computed values of the parameters depends on the number of data points, and the errors in the data. The sensitivity of the different parameters to errors may differ by orders of magnitude. A method of calculating the expected errors in the parameters is described, and the results of some applications of the method are presented.


Bradykinin modulation of isolated rabbit heart function is mediated by intrinsic cardiac neurons.
Bradykinin (BK) is an endogenous peptide exerting a potent influence on the behavior of the heart. The local regulatory mechanisms responsible for BK modulation of cardiac automaticity and contractility remain poorly understood. The role of the intrinsic cardiac nervous system (ICNS) in mediating the BK-induced regulatory effect was investigated. Heart rate (HR) and intramyocardial pressure (IMP) changes in response to BK (1.2-80 nmol) were studied in isolated rabbit hearts (n = 37). The intrinsic neural mechanisms underlying the cardiac effects of BK were characterized by use of atropine (ATR, 10(-6) M), timolol (TIM, 10(-5) M), hexamethonium (HEX, 10(-4) M), and tetrodotoxin (TTX, 10(-7) M). Modulation of beta-adrenergic tone by dobutamine (DOB, 1.6 x 10(-6) M) was used to expose the physiological importance of intrinsic cholinergic systems in mediating the cardiac action of BK. A single dose of BK induced an increase in IMP and a biphasic HR response. The negative chronotropic response to BK was correlated with negative HR change induced by nicotine activation of ICNS. BK-elicited 'bradycardia' was abolished by ATR and TTX, and attenuated (approximately 50%) by HEX. ATR and TTX potentiated the positive HR-response which was not affected by TIM. BK selectively antagonized [by 48.1(5.1)%] the DOB-induced tachycardia but did not modify the accompanied inotropic potentiation. These findings are the first demonstration that in the autonomically decentralized heart, the negative chronotropic action of BK is mediated by intrinsic cardiac cholinergic neurons. It would appear that the intrinsic neural network response, and not merely the BK-induced potentiation of cardiac postganglionic neural activity is involved in the local neuromodulatory action of BK. This intrinsic cardiac regulatory mechanism seems to play a major role in mitigating the adrenergically induced tachycardia, thus endowing this peptide with the capacity for cardioprotection.


Observational study of Interleukin-21 (IL-21) does not distinguish Kawasaki disease from other causes of fever in children.
Kawasaki disease (KD) is a febrile childhood vasculitis of unknown etiology. The diagnosis is highly concerning as over a quarter of children who fail to receive timely treatment with intravenous immunoglobulin (IVIG) will develop coronary aneurysms. Diagnosis relies on proper symptomatology and is supported by non-specific markers of inflammation. Previous studies have identified elevated plasma levels of interleukin-21 (IL-21) as a sensitive and specific biomarker in KD. The aim of this study is to assess the validity of IL-21 as a diagnostic biomarker for KD in febrile children in North America. Plasma samples were collected from children who presented to an urban Emergency Department in North America. IL-21 levels were measured using commercial ELISA kits in 12 KD versus 60 controls subjects. Our study shows that IL-21 levels were non-specifically elevated across all febrile children, irrespective of KD diagnosis. Length of fever prior to sample collection does not correlate with IL-21 levels. Other inflammatory markers and laboratory values were also compared to IL-21 and show no significant correlation. Since IL-21 is elevated non-specifically in this cohort, our data supports that IL-21 is not an appropriate biomarker for diagnosis of KD in North American pediatric populations.


The regional vulnerability to blockade of action potentials in organotypic hippocampal culture.
We investigated how blockade of spontaneous action potentials influenced the synaptogenesis by measuring the field population spike using hippocampal organotypic cultures. Although respective blockade of inhibitory and excitatory neurotransmission by picrotoxin and CNQX did not significantly induce cell death in all hippocampal area, sodium channel blocking drugs (tetrodotoxin or lidocaine) caused specific and severe damage and affected the formation of functional synapse in CA1 and the entorhinal cortex but not in CA3. It is suggested that the spontaneous action potentials would play a critical role during synaptogenesis.


Circadian disruption alters gut barrier integrity via a ß-catenin-MMP-related pathway.
We evaluated the mechanistic link between circadian rhythms and gut barrier permeability. Mice were subjected to either constant 24-h light (LL) or 12-h light/dark cycles (LD). Mice housed in LL experienced a significant increase in gut barrier permeability that was associated with dysregulated ß-catenin expression and altered expression of tight junction (TJ) proteins. Silencing of ß-catenin resulted in disruption of barrier function in SW480 cells, with ß-catenin appearing to be an upstream regulator of the core circadian components, such as Bmal1, Clock, and Per1/2. In addition, ß-catenin silencing downregulated ZO-1 and occludin TJ proteins with only limited or no changes at their mRNA levels, suggesting post transcriptional regulation. Indeed, silencing of ß-catenin significantly upregulated expression of matrix metallopeptidase (MMP)-2 and MMP-9, and blocking MMP-2/9 activity attenuated epithelial disruption induced by ß-catenin silencing. These results indicate the regulatory role of circadian disruption on gut barrier integrity and the associations between TJ proteins and circadian rhythms, while demonstrating the regulatory role of ß-catenin in this process.


A modified protocol for sex identification of in ovo avian embryos and its application as a management tool for endangered species conservation programs.
A simple, reliable, and safe protocol was developed for the collection of small amounts of blood from avian eggs of variable size and at early stages of development. Fifty eggs were used in the study; 40 were common chicken (Gallus domesticus) eggs, six were homing pigeon (Columba livia domestica) eggs, and four were burrowing owl (Athene cunicularia) eggs. Collection was attempted approximately halfway through incubation. The success rate for collection of blood or blood-tinged fluid from eggs was high, averaging 68% in the chicken eggs, 100% in the homing pigeon eggs, and 75% in the burrowing owl eggs. Collection did not affect subsequent hatchability. This blood could then be used to determine the sex of the embryo by utilizing a DNA probe or restriction fragment length polymorphism technique. Sex identification in ovo allowed the demographic management of small populations of birds within our institution.


Pathogenesis of Borna disease.
Borna disease represents a unique model of a virus-induced immunological disease of the brain. Naturally occurring in horses and sheep, the mechanisms of pathogenesis have been studied in experimental animals, namely in the rat. Many investigations have revealed that the infection of the natural hosts principally follows the same pathogenic pathways as observed in rats, leading to a severe encephalomyelitis. This affliction of the central nervous system results in severe neurological disorders that again, are fully comparable in laboratory animals to those in the natural and the different experimental hosts. In addition, alterations have been reported which are also based on the infection of the brain and do not result in the classical encephalitic clinical picture but rather in alterations of behavior. However, to all of our knowledge, the various clinical pictures of Borna disease are not caused by the infecting virus itself but rather by the hosts immune response towards it, i.e. by a virus-induced cell-mediated immunopathological reaction. The importance of virus-specific CD4+ T cells as exemplified by a cultured T cell line and of CD8+ T cells as shown by immunomodulatory substances and specific antibody treatment in vivo for the pathogenesis of acute Borna disease will be elucidated here. In addition, evidence will be provided that virus-specific CD8+ T cells are also responsible for the dramatic brain atrophy in the chronic phase of the disease in rats. Therefore, Borna disease not only lends itself exquisitely well to the study of the pathogenesis of an immunopathological disease of the brain but also represents one of the few models for immune-mediated tissue destruction that eventually leads to brain atrophy and clinically to dementia.


Molecular sensors for temperature detection during behavioral thermoregulation in turtle embryos.
Temperature sensing is essential for the survival of living organisms. Some reptile embryos can reposition themselves within the egg to seek optimal temperatures, but the molecular sensors involved in this temperature detection remain unknown. Here, we show that such thermotaxic behavior is directly determined by the activation of two heat-sensitive ion channels of the turtle: the transient receptor potential ankyrin 1 (MrTRPA1) and transient receptor potential vanilloid-1 (MrTRPV1). These two TRP channels were found to exhibit distinctive distributions among turtle dorsal root ganglion (DRG) neurons. Additionally, our laser irradiation assays illustrated that the heat activation thresholds of MrTRPA1 and MrTRPV1 are consistent with the mild (28-33°C) and noxious (>33°C) heat determined by behavioral tests, respectively. Further pharmacological studies have demonstrated that ligand-induced intervention of MrTRPA1 or MrTRPV1 is sufficient to mimic heat stimuli or block temperature signaling, causing changes in embryo movement. These findings indicate that the initiation of thermotaxic response in turtle embryos relies on a delicate functional balance between the heat activation of MrTRPA1 and MrTRPV1. Our study reveals, for the first time, a unique molecular mechanism underlying thermal detection: the two TRP channels act as a physiological tandem to control the thermotaxic behavior of turtle embryos.


A mathematical analysis of agonist- and KCl-induced Ca(2+) oscillations in mouse airway smooth muscle cells.
Airway hyperresponsiveness is a major characteristic of asthma and is generally ascribed to excessive airway narrowing associated with the contraction of airway smooth muscle cells (ASMCs). ASMC contraction is initiated by a rise in intracellular calcium concentration ([Ca(2+)](i)), observed as oscillatory Ca(2+) waves that can be induced by either agonist or high extracellular K(+) (KCl). In this work, we present a model of oscillatory Ca(2+) waves based on experimental data that incorporate both the inositol trisphosphate receptor and the ryanodine receptor. We then combined this Ca(2+) model and our modified actin-myosin cross-bridge model to investigate the role and contribution of oscillatory Ca(2+) waves to contractile force generation in mouse ASMCs. The model predicts that: 1), the difference in behavior of agonist- and KCl-induced Ca(2+) waves results principally from the fact that the sarcoplasmic reticulum is depleted during agonist-induced oscillations, but is overfilled during KCl-induced oscillations; 2), regardless of the order in which agonist and KCl are added into the cell, the resulting [Ca(2+)](i) oscillations will always be the short-period, agonist-induced-like oscillations; and 3), both the inositol trisphosphate receptor and the ryanodine receptor densities are higher toward one end of the cell. In addition, our results indicate that oscillatory Ca(2+) waves generate less contraction than whole-cell Ca(2+) oscillations induced by the same agonist concentration. This is due to the spatial inhomogeneity of the receptor distributions.


Radiation boost for synchronous solitary inguinal lymph node metastasis during neoadjuvant chemoradiotherapy for locally advanced rectal cancer.
Some patients with locally advanced rectal cancer (LARC) present with inguinal lymph node metastases without evidence of other systemic disease, known as solitary inguinal lymph node metastasis (SILNM). These patients may represent a distinct subset who have a more favorable prognosis and should be treated with curative intent. The optimal treatment strategy for these patients has not been determined. We retrospectively reviewed 16 consecutive LARC patients diagnosed between January 2017 and December 2019, who had SILNM, were treated with an inguinal lymph nodes (ILN) radiation boost with curative intent during neoadjuvant chemoradiotherapy (nCRT) and underwent total mesorectal excision (TME). We used Kaplan-Meier survival curves to calculate survival rates, and recorded radiation-related toxicity. None of these 16 patients developed pelvic or inguinal recurrences, and 3 of the patients developed distant metastases. The 3-year overall survival rate and locoregional relapse-free survival rate were both 100%. The 3-year disease-free rate and distant metastasis-free survival rate were both 81.3%. Of 5 patients who had ILN dissection for suspicious ILNs after neoadjuvant treatment, 2 had residual nodal tumor confirmed. Grade 3 toxicity was found in 5 patients, and no patients had lymphedema or other grade 4 or 5 toxicities. In LARC patients with synchronous SILNM, a radiation boost to the ILNs during nCRT achieved excellent local control with acceptable toxicity. Though the optimal treatment strategy remains unclear, nCRT with an ILN radiation boost prior to TME may be a reasonable therapeutic approach to consider for this subset of patients.


Cross-cultural adaptation of The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire: A methodological systematic review.
The Japanese Orthopaedic Association Back Pain Evaluation Questionnaire (JOABPEQ) is a reliable and sensitive measure of disability to determine functional status and evaluate curative effects in low back pain, it has now been cross-cultural translated into many other languages and adapted for use in different countries. We aim to evaluate the translation procedures and measurement properties of cross-cultural adaptations of the JOABPEQ. Studies related to cross-cultural adaptation of the JOABPEQ in a specific language/culture were searched in PubMed, Embase, CINAHL, SciELO, PsycINFO, SinoMed, and Web of Science from their inception to March 2022. The Guidelines for the Process of Cross-Cultural Adaptation of Self-Report Measures and the Consensus-based Standards for the Selection of Health Status Measurement Instruments guideline were used for evaluation. Nine different versions of cross-cultural JOABPEQ adaptations in 8 different languages/cultures were included. The adaptation process was not strictly performed, such as standard forward translation and expert committee review were rarely reported. Content validity (8/9), floor and ceiling effects (3/9), reliability (4/9), and interpretability (6/9) were assessed in most of the adaptations, while agreement (2/9), responsiveness (2/9), and the internal consistency (2/9) were not. JOABPEQ can replace functional and quality of life score to reduce the burden of scientific research. We recommend Persian-Iranian, simplified Chinese-Chinese Mandarin, Thai and Gunaydin G's Turkish adaptations for application. The numerical pain rating scale/visual analogue scale in low back pain and lower extremities, as well as numbness in lower extremities could not be neglected in JOABPEQ adaptations.


A qualitative study of infection prevention and control practices in the maternal units of two Ghanaian hospitals.
Healthcare-associated infections (HAIs) remain a common challenge in healthcare delivery, with a significant burden in low- and middle-income countries. Preventing HAIs has gained enormous attention from policy makers and healthcare managers and providers, especially in resource-limited settings. Despite policies to enforce infection prevention and control (IPC) measures to prevent HAIs, IPC compliance remains a challenge in hospital settings. In this study, we explore the experiences of healthcare providers and women in the post-natal phase and investigate factors influencing IPC practices in two hospitals in Ghana. The study used a qualitative approach involving semi-structured interviews, focus group discussions, and observations among healthcare providers and women in the postnatal phase in two maternity units from January 2019 to June 2019. Interviews were recorded and transcribed verbatim for thematic analysis. The data sets were uploaded into the qualitative software NVivo 12 to facilitate coding and analysis. Healthcare providers were driven by the responsibility to provide medical care for their patients and at the same time, protect themselves from infections. IPC facilitators include leadership commitment and support, IPC training and education. Women were informed about IPC in educational talks during antenatal care visits, and their practices were also shaped by their background and their communities. IPC barriers include the poor documentation or 'invisibility' of HAIs, low prioritization of IPC tasks, lack of clear IPC goals and resources, discretionary use of guidelines, and communication-related challenges. The findings demonstrate the need for relevant power holders to position themselves as key drivers of IPC and develop clear goals for IPC. Hospital managers need to take up the responsibility of providing the needed resources and leadership support to facilitate IPC. Patient engagement should be more strategic both within the hospital and at the community level.


Recurrent noisy pneumothorax mimicking pericarditis.
Sounds related to the cardiac cycle may have an extra-cardiac origin. We report a case of recurrent noisy pneumothorax producing a loud rub, audible at a distance from the patient and initially diagnosed as pericarditis. The sounds and their mechanisms of production in this condition are also discussed.


Intrarenal pressure following pyeloplasty or percutaneous surgery.
In a study of 37 patients it was shown that recording the intrapelvic pressure is a safe and reliable means of judging the best time to remove a nephrostomy tube. No post-operative complications were encountered and the procedure has the added advantage of avoiding the use of X-rays.


Clinical outcomes of maternal and neonate with COVID-19 infection - Multicenter study in Saudi Arabia.
To this end, the influence of COVID-19 on pregnant women and their neonates is not completely clear. Therefore, the main aim of this study is to investigate maternal and neonatal clinical outcomes with confirmed COVID-19 infection. Besides, it investigates the likelihood of vertical transmission of COVID-19 infection from pregnant women to their neonates. A retrospective descriptive study was conducted in three medical centers during the period from March to November 2020. Data were collected from the available medical records in the respective hospitals using a standardized questionnaire on maternal and neonatal clinical outcomes. All pregnant women with confirmed COVID-19 infection across the three hospitals and their neonates were eligible to participate in this study. Descriptive statistics were presented as a median and interquartile range (IQR) or frequencies and percentages as appropriate using SPSS 24.0 software. This study has identified a total of 288 pregnant women with confirmed COVID-19 infection over the study period of a median age of 30 years and median GA at diagnosis 38 weeks (IQR: 39 -33) as well as 27% of them were obese (n=78). The majority of pregnant women were symptomatic with cough (n=92, 31.9%) being the most frequent COVID-19 symptom followed by fever and dyspnea (n=36, 12.5%). Two-hundred and four pregnant delivered (70.84%) and caesarean sections were prevalent among 35.8% of them. The most common adverse pregnancy outcome was premature (n=31, 15.5%), followed by fetal distress (n=13, 6.5%), preeclampsia (n=4, 2.0%), and one pregnant woman died. The laboratory results exhibit that temperature higher than 38 (n=27), leukopenia (n=19), neutropenia (n=54), ALT (n=12), AST (n=31), and thrombocytopenia (n=35) were less frequent among pregnant women while lymphopenia (n=126), hemoglobin levels lower than 13.0 (n=218), deceased albumin levels (n=195) were most frequent among them. However, a small proportion of pregnant women were admitted to the ICU (3.8%). The most frequent maternal treatments were antibiotics (n=81), antiviral (n=49), and corticosteroid (n=24). Of 204 neonates, four had died and all the remaining neonates were alive. The median gestational age at delivery was 39 weeks (IQR: 35-40). Most neonates had normal laboratory results. However, 14 had lymphopenia (7.0%), 22 had neutropenia (11.0%), and 11 had thrombocytopenia (5.5%). Four infants had low hemoglobin levels of less than 13.0 (2.0%) and 81 had hyperbilirubinemia (e.g., total bilirubin of higher than 23; 40.5%). Approximately less than one-half of neonates required admission to the NICU (n=86, 43%), 7% of them required respiratory support of mechanical ventilation, and none of them get infected with COVID-19 disease. This multicenter study suggests that the majority of pregnant women had mild or moderate disease symptoms. Nevertheless, this study did not find any evidence of possible vertical transmission of COVID-19 infection from mothers to their babies. This study may provide a baseline for further studies focusing on investigating long-term maternal and neonate's outcomes and possible vertical transmission of COVID-19 from mothers to their newborn babies.


Memory for script actions: effects of relevance and detail expectancy.
Script actions that varied both in relevance to the script and in the expectancy of their details were developed. In Experiment 1, recall of these actions was tested. Actions of medium relevance were recalled better than actions of high or low relevance, whether or not details were presented. However, the unexpected details themselves were recalled better than the expected details. In Experiment 2, recognition was lowest for high-relevance actions but medium- and low-relevance actions did not differ. Actions with unexpected details were recognized better than actions with expected details, which tended to be better than generic actions. The results were interpreted as showing that both the relevance and the expectancy of the details in script actions are important in memory, but that the two dimensions may play different roles.


Heterosexual Cisgender Men Partnered with Transgender Women Exhibit Higher HIV/STI Sexual Risk than Their Gay, Bisexual, and Queer Counterparts: Findings from a U.S.-Based Convenience Sample Recruited Online.
Cisgender men are frequently vectors for HIV transmission among transgender women. Despite this, the correlates of sexual risk among these men remain under-examined. The purpose of the present study was to explore potential differences in relationship characteristics, sexual risk-taking, and risk-reduction strategies among cisgender men partnered with transgender women. The study utilized secondary screening data provided by adult cis men who reported being in a primary relationship with a trans woman (N = 710). Gay men (18%) were comparatively older, and most likely to report both HIV seropositivity and committed pairings. Heterosexual men (14%) were more likely to report exchange sex, briefer relationships, extra-dyadic sex, lesser serostatus awareness or PrEP uptake. Queer men (7%) were youngest, and most likely to access PrEP. Heterosexual cis men with trans women partners may be subject to unique socio-cultural drivers of sexual risk, such as heteronormative pressures and relationship stigma.


A nebulizer interface for liquid chromatography - Flame ionization detection: Development and validation.
Within this study, a novel liquid chromatography (LC)/flame ionization detector (FID) interface was improved. In contrast to previously published interface concepts, the main nebulizer body and the transfer capillary was made of stainless steel. Previously reported problems such as blocking of the transfer capillary were investigated. The simple design of the here presented nebulizer interface allows a convenient handling and the exchangeability of all nebulizer parts targets fast maintenance during routine analysis. A significant advantage is the capability to implement the novel interface into most common gas chromatography (GC)/FID systems. The effects of the instrumental parameters such as backpressure, gas flow, distance between nebulizer nozzle and FID collector or FID temperature on the signal were analyzed and optimized. The influence of the nebulizer material on flame stability and capillary blockage, a well-known problem of former coupling systems, was investigated, too. Finally, the novel interface was validated for the analysis of selected compounds known from literature. Obtained results for chromatographic separation of the alcohols propanol, butanol, pentanol and hexanol, used within previous studies in the field of LC/FID coupling are shown. Limits of detection (LODs), sensitivity and linearity found within this work are compared with LC/FID interfaces developed in the past.