Health-related quality of life in persons with long-standing spinal cord injury.
A cross-sectional study of all patients with traumatic SCI admitted to Sunnaas Rehabilitation Hospital, Norway between 1961 and 1982. To assess health-related quality of life (HRQOL) in persons with long-standing traumatic spinal cord injury (SCI) in Norway. Sunnaas Rehabilitation Hospital, Norway. Survey data and clinical examination of 165 persons with traumatic SCI of more than 20 years duration. HRQOL was assessed with the Norwegian 36-item short-form [corrected] (SF-36) Health Survey. The SF-36 results were compared with Norwegian norm data adjusted to age and gender. Differences in HRQOL between subgroups were studied. The persons with SCI exhibited significantly decreased HRQOL in the subscales for Physical Functioning, Bodily Pain, General Health, Social Functioning [corrected] and Vitality compared to the normal population. There were relatively small differences in HRQOL when comparing persons with paraplegia versus tetraplegia and persons with AIS (ASIA Impairment Scale; ASIA, American Spinal Injury Association) A-C versus D-E. Employed persons reported higher HRQOL compared to unemployed persons. HRQOL of individuals reporting health problems or symptoms was worse than those of individuals reporting no health problems at all. HRQOL is decreased in persons with long-standing SCI and especially in persons with comorbidity conditions.


The effects of intraperitoneal calcitriol on calcium and parathyroid hormone.
Parathyroid suppression by intraperitoneal calcitriol (1,25(OH)2D3) during peritoneal dialysis. The purpose of this study was to determine if parathyroid hormone (PTH) suppression could be achieved by increasing calcium mass transfer (Ca MT) with high dialysate Ca (4 mEq/liter) or via intraperitoneal (i.p.) 1,25(OH)2D3 in patients undergoing continuous ambulatory peritoneal dialysis. Eleven patients were dialyzed for two months with standard Ca dialysate (3.5 mEq/liter) followed by two months with 4.0 mEq/liter Ca, then by three months of i.p. 1,25(OH)2D3. During the latter period, patients were randomized to groups whose dialysate contained either 3.5 mEq/liter or 4.0 mEq/liter Ca. We found that 4.0 mEq/liter Ca dialysate more than doubled Ca MT (37 +/- 17 mg/day to 84 +/- 6 mg/day) leading to a modest fall (P less than 0.05) in PTH levels (84 +/- 5.5% of controls). Ionized calcium levels did not change. With i.p. 1,25(OH)2D3, however, ionized calcium rose significantly (P less than 0.001) leading to a decline in PTH levels to 53.9 +/- 7.9% of control values. Serum 1,25(OH)2D3 levels rose from undetectable to 47.7 +/- 7.2 pg/dl (normal range 20 to 35). These studies indicate that increasing Ca MT using a 4.0 mEq/liter Ca dialysate leads to a small reduction in PTH concentrations. On the other hand, i.p. 1,25(OH)2D3 is well absorbed into the systemic circulation, raises ionized calcium levels, and leads to a marked suppression of PTH. Thus, i.p. 1,25(OH)2D3 may be a simple and effective means to suppress secondary hyperparathyroidism in patients undergoing CAPD.


Platelet-leukocyte deregulated interactions foster sterile inflammation and tissue damage in immune-mediated vessel diseases.
Platelets and leukocytes co-localize and interact at sites of vessel injury, haemorrhage, thrombosis and inflammation. Recent studies have highlighted the role of local cues in the interaction between the two cell populations, including the exposure of anionic phospholipids and the release of Damage Associated Molecular Patterns (DAMPs) by activated platelets, the release of the prototypical tissue pentraxin PTX3 by neutrophils, as well as the generation of polarized clusters of neutrophil ß(2) integrins. In turn, the reciprocal activatory cross-talk between platelets and leukocytes contributes to the generation of thrombo-inflammatory lesions and of vascular injury. Here we will discuss the implications of these results for the pathogenesis and the clinical features of self-sustaining immune-mediated vessel diseases.


Non-ingested Intraperitoneal Foreign Body Extraction by Transumbilical Endoscopic Surgery in a 2-year-Old Girl.
In this article, we present an unusual case of a girl who had a mass present in the right lower quadrant of the abdomen and imaging analysis showed that to be a sewing needle. Patient was admitted electively and taken to the operation theater for removal of a foreign body under general anesthesia. The needle was extracted with transumbilical endoscopic surgery (TUES) without any evidence of intra-abdominal organ injury and with a good long-term cosmetic outcome. This case highlights the subtleties of TUES in the management of intra-abdominal foreign bodies in children including rare causes such as non-ingested foreign bodies.


The ecological impact of liquid chromatographic methods reported for bioanalysis of COVID-19 drug, hydroxychloroquine: Insights on greenness assessment.
Hydroxychloroquine is a drug that has been widely used during the early stages of COVID-19 pandemic. Different liquid chromatographic methods have been reported for the analysis of hydroxychloroquine in various biological matrices such as human plasma, serum, whole blood, oral fluid, rat plasma and tissues. In this comparative study, the most popular tools used for assessing the greenness profile: National Environmental Methods Index (NEMI), Eco-Scale Assessment (ESA), Green Analytical Procedure Index (GAPI) and Analytical Greenness metric (AGREE) were utilized to evaluate the ecological impact of eighteen liquid chromatographic methods developed for the bioanalysis of COVID-19 drug; hydroxychloroquine. NEMI is the simplest tool for evaluating the greenness profile of developed methods, but it is the least informative approach as all the reported methods had the same NEMI pictograms. On the other hand, GAPI is a dependable tool providing a complete picture about the method greenness starting from sampling until the final determination. ESA and AGREE tools are digitally presented and more easily applied. Therefore, their utilization for greenness assessment is highly recommended. Selection of the highest eco-friendly analytical procedure is of a paramount importance for protecting human health and the environment. Considering the greenness of the analytical procedures is highly recommended before proceeding to routine use in order to minimize the chemical hazards to the environment. The most eco-friendly analytical procedures for the analysis of hydroxychloroquine in biological samples according to ESA, GAPI and AGREE tools will be highlighted and discussed.


Advances in biosensing strategies for HIV-1 detection, diagnosis, and therapeutic monitoring.
HIV-1 is a major global epidemic that requires sophisticated clinical management. There have been remarkable efforts to develop new strategies for detecting and treating HIV-1, as it has been challenging to translate them into resource-limited settings. Significant research efforts have been recently devoted to developing point-of-care (POC) diagnostics that can monitor HIV-1 viral load with high sensitivity by leveraging micro- and nano-scale technologies. These POC devices can be applied to monitoring of antiretroviral therapy, during mother-to-child transmission, and identification of latent HIV-1 reservoirs. In this review, we discuss current challenges in HIV-1 diagnosis and therapy in resource-limited settings and present emerging technologies that aim to address these challenges using innovative solutions.


Paracrystals of myosin rod.
To help understand the packing of myosin tails in the backbone of the vertebrate striated muscle thick filament, paracrystals of myosin rod, a proteolytic fragment corresponding to the whole myosin tail, have been examined by electron microscopy and image analysis. Two types of paracrystal were observed. Type I paracrystals were similar to those seen by Moos et al. (1975; J. molec. Biol. 97, 1-9). These showed a 14-nm axial repeat, but yielded no other structural information. Type II paracrystals were long, flexible ribbons with more regularity. When negatively stained they exhibited a weak 43-nm axial striation and appeared to be composed of a layer of narrow filaments. Optical diffraction showed that the paracrystals had a rectangular unit cell of dimensions 43 nm axially and 12.4 nm laterally. Transverse sections indicated a paracrystal depth similar to the lateral dimension of the unit cell. Each unit cell contained two filaments arranged antiparallel and related by a two-fold screw axis perpendicular to the length, and in the plane of the ribbon. The filaments probably consist of parallel rod molecules related by axial displacements of 43 nm and higher multiples of 43 nm. The nature of these paracrystals indicates that the myosin tail alone can form structures like thick filament subfilaments. Their structure, based on distinguishable parallel and antiparallel rod interactions, was sensitive to pH and divalent cations in a similar way to the ionic effects on the structure of thick filaments. This behaviour suggests that some of the interactions present in the paracrystal are the same as those in the thick filament.


Treatment of experimentally induced cytauxzoonosis in cats with parvaquone and buparvaquone.
The efficacy of parvaquone (Clexon) and buparvaquone (Butalex) in treating experimentally induced feline cytauxzoonosis was explored. Domestic cats were inoculated subcutaneously with blood from a cat infected with Cytauxzoon felis and treated daily with either 20 or 30 mg kg-1 parvaquone, or 5 or 10 mg kg-1 buparvaquone, beginning on either the first day parasites were detected in peripheral blood, or 2 days after the onset of parasitemia. Fifteen cats were treated and all but one died due to the infection. Unexpectedly, one of two non-treated, infected control cats survived. Although parvaquone and buparvaquone are the treatments of choice for a related hemoprotozoan parasite causing theileriosis in African cattle, wer concluded that at the dosages and regimes tested, these drugs are not effective treatments for feline cytauxzoonosis. Blood from the two surviving cats was inoculated into naive cats and in these animals clinical disease or death were not observed. The latter two naive recipient cats were then inoculated with a lethal dose of viable, frozen C. felis and both died, thereby indicating that blood from surviving cats did not induce an infectious state that resulted in immunity. The two cats that survived the acute infection were subsequently challenged with a lethal inoculum of C. felis; they showed no clinical signs of cytauxzoonosis and were obviously immune to reinfection.


Chinmo is the larval member of the molecular trinity that directs Drosophila metamorphosis.
The molecular control of insect metamorphosis from larva to pupa to adult has long been a mystery. The Broad and E93 transcription factors, which can modify chromatin domains, are known to direct the production of the pupa and the adult, respectively. We now show that chinmo, a gene related to broad, is essential for the repression of these metamorphic genes. Chinmo is strongly expressed during the formation and growth of the larva and its removal results in the precocious expression of broad and E93 in the first stage larva, causing a shift from larval to premetamorphic functions. This trinity of Chinmo, Broad, and E93 regulatory factors is mutually inhibitory. The interaction of this network with regulatory hormones likely ensures the orderly progression through insect metamorphosis.


Serum amyloid A levels associated with gastrointestinal manifestations in Henoch-Schönlein purpura.
Henoch-Schönlein purpura (HSP) is considered as an immune-mediated inflammatory disease. Serum amyloid A (SAA) is an acute-phase protein with proinflammatory effects. We investigated the levels of SAA in HSP patients and examined whether SAA levels are associated with organ involvement and disease severity. Seventy patients with HSP, including 35 with nephritis (HSPN) and 35 without HSPN, and 20 controls were recruited in our study. SAA levels were measured and other clinical laboratory parameters, including C-reactive protein, erythrocyte sedimentation rate, complement 3 (C3), C4, and immunoglobulin (Ig) A, were recorded. SAA levels were not found to be independently associated with renal, joint involvement, and disease severity. However, higher SAA levels were observed in HSP patients with gastrointestinal (GI) manifestations (p=0.006, p (c)=0.048). Moreover, the levels of SAA were significantly associated with duration of disease (p<0.005, p(c)<0.04). Our findings suggested that SAA was significantly associated with disease duration and GI manifestations in HSP patients.


[The hemodynamics of the lung circulation of minipigs after experimentally-caused Sedlarik's pulmonary embolism. I. Sedlarik's pulmonary embolism model in comparison to existing embolism models].
The necessity of a clinical relevant pulmonary embolism model is described because of the international importance and the consequence for certain special branches. The multifarious pathophysiologic mechanism in the human requires an approximation of the model. The pulmonary embolism model according to Sedlarik approaches these demands and it became the basis of this study.


Deviation versus violation plots: A new technique for assessing the self-consistency of NMR data.
A new method has been developed to test the self-consistency of distance constraints derived from NOESY spectra. The technique is based on the premise that the further the atomic coordinates of any given structure vary from the 'correct' structure, the more NOE violations will occur in that structure. This relationship is quantified by plotting the deviation of each structure against the sum of the residual NOE violations. This type of plot is called a DVplot, which is generated by the following means: first the experimental constraints are used to generate a set of structures, then the amount of deviation and violation is quantified for each structure. The deviation of each structure is derived from the root-mean-squared deviation (rmsd) between each structure and the average structure. Violations are quantified for each structure using the new terms S1, S2, and S3. These terms measure the sum of all residual NOE violations greater than 0.1 A, 0.2 A, and 0.3 A, respectively. DVplots are used to show that for series of structures calculated from a single set of NMR constraints, there is an approximate linear correlation between the rmsd and each of the three sums, S1, S2, and S3. Furthermore, it is proposed that the x-intercepts derived from the three plots of S1, S2, and S3 will converge if the NOE constraints are selfconsistent. The new technique is applied to five different proteins using both experimental and simulated constraint sets.


Assessing the composition of the plasma membrane of Leishmania (Leishmania) infantum and L. (L.) amazonensis using label-free proteomics.
Protozoan parasites of the genus Leishmania are causative agents of leishmaniasis, a wide range of diseases affecting 12 million people worldwide. The species L. infantum and L. amazonensis are etiologic agents of visceral and cutaneous leishmaniasis, respectively. Most proteome analyses of Leishmania have been carried out on whole-cell extracts, but such an approach tends to underrepresent membrane-associated proteins due to their high hydrophobicity and low solubility. Considering the relevance of this category of proteins in virulence, invasiveness and the host-parasite interface, this study applied label-free proteomics to assess the plasma membrane sub-proteome of L. infantum and L. amazonensis. The number of proteins identified in L. infantum and L. amazonensis promastigotes was 1168 and 1455, respectively. After rigorous data processing and mining, 157 proteins were classified as putative plasma membrane-associated proteins, of which 56 proteins were detected in both species, six proteins were detected only in L. infantum and 39 proteins were exclusive to L. amazonensis. The quantitative analysis revealed that two proteins were more abundant in L. infantum, including the glucose transporter 2, and five proteins were more abundant in L. amazonensis. The identified proteins associated with distinct processes and functions. In this regard, proteins of L. infantum were linked to metabolic processes whereas L. amazonensis proteins were involved in signal transduction. Moreover, transmembrane transport was a significant process among the group of proteins detected in both species and members of the superfamily of ABC transporters were highly represented. Interestingly, some proteins of this family were solely detected in L. amazonensis, such as ABCA9. GP63, a well-known virulence factor, was the only GPI-anchored protein identified in the membrane preparations of both species. Finally, we found several proteins with uncharacterized functions, including differentially abundant ones, highlighting a gap in the study of Leishmania proteins. Proteins characterization could provide a better biological understanding of these parasites and deliver new possibilities regarding the discovery of therapeutic targets, drug resistance and vaccine candidates.


Experimental cerebral infarction. Part 3: Protective effect of mannitol in thalamic infarction in dogs.
Whether or not mannitol can prevent infarctions in ischemic brain tissues was investigated utilizing the thalamic infarction model in dogs. Twenty dogs were divided into equal control and mannitol treatment groups. Temporary 4 vessel clipping for 60 minutes was adopted as the standard procedure for both groups. The only difference between the groups was the administration of 2 g/kg of mannitol before the arterial occlusion. In the controls, 6 of 10 dogs showed infarctions verified by histological changes at the seventh post-ischemic day. In the mannitol group only 1 dog in 10 showed infarction. The difference is statistically significant.


Construction of a shuttle vector for the overexpression of recombinant proteins in Actinobacillus succinogenes.
To express foreign proteins in Actinobacillus succinogenes, a shuttle vector was constructed based on the Actinobacillus pleuropneumoniae-Escherichia coli shuttle vector, pGZRS-19. We demonstrated that A. succinogenes is transformed by electroporation at reasonably high efficiency, that pGZRS-19 is stable in A. succinogenes, and that the ampicillin resistance gene carried by pGZRS-19 is expressed in A. succinogenes. Three steps were then required to develop our A. succinogenes-E. coli shuttle vector. (i) The constitutively expressed A. succinogenes phosphoenolpyruvate carboxykinase gene, pckA, was cloned and sequenced. (ii) Its promoter region and ribosome-binding site were subcloned into pGZRS-19. (iii) Finally, the ColE1 origin of replication was added to the vector to increase its stability in E. coli. High levels of A. succinogenes phosphoenolpyruvate carboxykinase, E. coli NADP-dependent malic enzyme, and Bacillus subtilis NAD-dependent malic enzyme activities detected in recombinant A. succinogenes strains confirmed that A. succinogenes and foreign proteins could be expressed in A. succinogenes under control of the A. succinogenes pckA promoter carried by pLGZ920. A. succinogenes is sensitive to chloramphenicol and tetracycline. Although not expressed from their own promoters, the Tn9 chloramphenicol and the Tn10 tetracycline resistance genes are expressed under control of the pckA promoter, and they can be used as additional selection markers in A. succinogenes.


Characteristics of auditory brainstem responses in ground squirrels.
Auditory brainstem responses (ABRs) were characterized at 37 degrees C in ground squirrels (Citellus lateralis) which were implanted with recording screws to record ABRs, and a thermistor to record brain temperature. After two weeks ground squirrels were reanesthetized and tone pips and clicks were delivered through a TDH-49 headphone. Recorded ABRs were found to vary in a predictable manner as a function of stimulus frequency and intensity. At intensities above 50 dB SPL, ABRs could be recorded over the range tested (2-32 kHz). An 8 kHz tone pip was the best frequency for recording ABRs at the lowest stimulus intensities. Latencies decreased as stimulus frequencies increased from 4 kHz to 32 kHz.


Barriers to high-quality primary reproductive health services in an urban area of Iran: views of public health providers.
to explore public primary reproductive health providers' views on their own roles and tasks in their present organisation, and the perceived barriers to providing high-quality services. a qualitative approach using semi-structured, audio-taped focus group discussions (FGDs). The discussions were held in Farsi or Turkish, transcribed verbatim, translated into English and analysed using content analysis. family health units of public health facilities, Tabriz, Iran. two FGDs with 12 midwives and two FGDs with eight other family health providers working at the facilities. the providers identified the most satisfying part of their duties as working with clients. A dominant theme in all FGDs was the providers' frustration about a number of factors, most of which were beyond their control. The identified system and organisational barriers were grouped into five categories: multiplicity of tasks and incompatibility with the providers' own basic training; suboptimal supervision and management; too little time for clients; lack of privacy and appropriate materials for education and counselling; and inadequate opportunities for continuing education. this study highlighted the providers' satisfaction in working with clients, and their dissatisfaction with not being used to the best of their capabilities due to a number of systemic and organisational barriers. based on these findings, multifaceted interventions seem to be necessary to improve staff productivity and service quality. The interventions should include needs-based pre-service education, supportive supervision and management, provision of educational materials, simplifying record management, and appointing more staff in socio-economically deprived areas. Research is needed to identify the best way to integrate the services, as well as basic and continuing educational needs of staff.


Colorimetric determination of As(III) based on 3-mercaptopropionic acid assisted active site and interlayer channel dual-masking of Fe-Co-layered double hydroxides with oxidase-like activity.
A colorimetric method is described for the determination of As(III). It is based on the use of 3-mercaptopropionic acid (3-MPA) assisted active site and interlayer channel dual-masking of oxidase-like Fe-Co-layered double hydroxides (Fe-Co-LDH). The Fe-Co-LDH acts as an oxidase-mimicking nanozyme with high activity. It catalyzes the oxidation of colorless 3,3'5,5'-tetramethylbenzidine (TMB) to form a blue product (oxTMB) with an absorption maximum at 652 nm. It is found that As(III) firmly anchors onto the Fe* sites of the 3-MPA-modified Fe-Co-LDH via forming a stable Fe─As(III)─3-MPA─As(III)─Fe structure. This results in masking the active sites and interlayer channels of the Fe-Co-LDH nanozyme. As a result, the presence of As(III) as well as 3-MPA specifically inhibit the LDH-catalyzed chromogenic reaction. Based on the above principle, a colorimetric assay was designed for the determination of As(III). It provided linear response in the 0.10~8.33 μM As(III) concentration range and a detection limit as low as 35 nM. The assay was applied to the quantitation of As(III), even in the presence of potential interferents including As(V), Hg(II) and Pb(II), in environmental and drinking water samples. Graphical abstractSchematic illustration of the As(III) sensing mechanism based on 3-mercaptopropionic acid (3-MPA) assisted active site and interlayer channel dual-masking of Fe-Co-layered double hydroxides (Fe-Co-LDH) with oxidase-like activity. 3-MPA with sulfhydryl and carboxyl groups can assist As(III) to firmly anchor onto the Fe* sites inside the interlayer channels of the Fe-Co-LDH via forming a Fe─As(III)─3-MPA─As(III)─Fe structure, thus selectively resulting in a significant suppression of the chromogenic reaction.


Colloidal Quantum Dot Infrared Lasers Featuring Sub-Single-Exciton Threshold and Very High Gain.
The use of colloidal quantum dots (CQDs) as a gain medium in infrared laser devices has been underpinned by the need for high pumping intensities, very short gain lifetimes, and low gain coefficients. Here, PbS/PbSSe core/alloyed-shell CQDs are employed as an infrared gain medium that results in highly suppressed Auger recombination with a lifetime of 485 ps, lowering the amplified spontaneous emission (ASE) threshold down to 300 µJ cm-2 , and showing a record high net modal gain coefficient of 2180 cm-1 . By doping these engineered core/shell CQDs up to nearly filling the first excited state, a significant reduction of optical gain threshold is demonstrated, measured by transient absorption, to an average-exciton population-per-dot 〈Nth 〉g of 0.45 due to bleaching of the ground state absorption. This in turn have led to a fivefold reduction in ASE threshold at 〈Nth 〉ASE = 0.70 excitons-per-dot, associated with a gain lifetime of 280 ps. Finally, these heterostructured QDs are used to achieve near-infrared lasing at 1670 nm at a pump fluences corresponding to sub-single-exciton-per-dot threshold (〈Nth 〉Las = 0.87). This work brings infrared CQD lasing thresholds on par to their visible counterparts, and paves the way toward solution-processed infrared laser diodes.


Autonomy and freedom of choice in prenatal genetic diagnosis.
An increase in autonomy and freedom is often considered one of the main arguments in favour of a broad use of genetic testing. Starting from Gerald Dworkin's reflections on autonomy and choice this article examines some of the implications which accompany the increase in choices offered by prenatal genetic diagnosis. Although personal autonomy and individual choice are important aspects in the legitimation of prenatal genetic diagnosis, it seems clear that an increase in choice offered by prenatal genetic diagnosis also leads to various implications that may negatively influence the freedom of the persons involved.


Five variants of the beta-globin gene without clinical or hematological effects: Hb Maryland [beta 47(CD6)Asp-->His], Hb Kent [beta 37(C3)Trp-->Cys], Hb Visayan [beta 136(H14)Gly-->Cys], Hb Cutlerville [beta 138(H16)Ala-->Val] and Hb Hornchurch [beta 43(CD2)Glu-->Lys].
We report on five hemoglobin (Hb) beta chain variants that were initially identified either by electrophoretic, chromatographic or isoelectric focusing (IEF) methods. These variants do not appear to be associated with clinical or hematological abnormalities. All variants were confirmed by DNA sequence analysis.


A Pilot Mind-Body Resiliency Intervention Targeting Fear of Recurrence among Cancer Survivors.
Interventions for fear of recurrence (FOR) of cancer have nominal effects, perhaps due to limited integration of empirically supported skills. This pilot trial tested the acceptability and feasibility of a multimodal, mind-body resiliency intervention targeting FOR among survivors of various cancers. Early stage cancer survivors 3-30 months post-treatment were recruited to participate in an eight-session in-person mind-body resiliency group intervention that taught relaxation skills, cognitive-behavioral techniques, healthy lifestyle behaviors, mindfulness meditation, and positive psychology skills all targeted for FOR. Primary outcomes were feasibility (enrollment rate, session attendance, survey completion, skills practice) and acceptability (enjoyableness, convenience, helpfulness, relevance). Patient-reported outcomes (FOR, uncertainty intolerance, cancer-related uncertainty, perceived stress, resiliency, positive affect, and coping skills) were collected at baseline, post-intervention, +1 month, and +3 months. Exit interviews assessed survivors' reported benefits. Participants (N = 4 groups, 23 survivors, enrollment response rate = 58%) included survivors of seven common cancer types who were on average 12 months post-treatment. Attendance was high (M = 6.1 sessions), and 96% of survivors completed all surveys. Sustained increases in relaxation skills practice 3+ days/week were reported (baseline = 16%, post-intervention = 76%, +3 months = 71%). Most sessions (87%) were rated as highly or very highly acceptable. Moderate-to-large (d = 0.87) improvements in FOR severity were observed post-intervention (p < .01) and across assessments (p < .01), with similar changes observed in other patient-reported outcomes. Exit interviews revealed behavioral, cognitive, emotional, and existential benefits. The targeted mind-body resiliency intervention shows promising acceptability, feasibility, and favorable changes in FOR and coping skills practice. Further adaptation and testing in a randomized trial are warranted. ClinicalTrials.govRegistration Number: NCT03695406.


Ecthyma Gangrenosum-Like Lesions Secondary to Methicillin-Sensitive Staphylococcus aureus in an Immunocompetent Child.
We describe a previously healthy 15-month-old girl who developed ecthyma gangrenosum (EG)-like lesions secondary to methicillin-sensitive Staphylococcus aureus (MSSA). Her systemic symptoms and negative blood cultures suggested MSSA toxin-mediated effects. When toxin-mediated systemic symptoms accompany such lesions, pathogens other than Pseudomonas aeruginosa should be considered.


Isolation and nucleotide sequence analysis of tRNAAlaGGC from Escherichia coli K-12.
An alanine tRNA with the anticodon 5'-GGC-3' has been identified in Escherichia coli K-12. It is the first sequenced alanine tRNA with G in the 5' position of the anticodon. tRNAAlaGGC has A in the "semi-invariant" position 32. At the "invariant" position 8 we observed both U and another, unknown, nucleoside.


The epithelium of human hydrosalpinges: a light optical and scanning electron microscopic study.
Multiple tubal biopsies from 21 patients with thin-walled dilated hydrosalpinges and from 12 patients with thick-walled fibrous hydrosalpinges were studied. All the biopsies were examined by light microscopy and scanning electron microscopy and the ciliated surface area at multiple locations measured by planimetry. These biopsies were compared with control biopsies taken from 13 normal women at varying stages of the menstrual cycle.


One Pot Synthesis of Micromolar BACE-1 Inhibitors Based on the Dihydropyrimidinone Scaffold and Their Thia and Imino Analogues.
A library of dihydropyrimidinones was synthesized via a "one-pot" three component Biginelli reaction using different aldehydes in combination with β-dicarbonyl compounds and urea. Selected 2-thiooxo and 2-imino analogs were also obtained with the Biginelli reaction from thiourea and guanidine hydrochloride, respectively. The products were screened in vitro for their β-secretase inhibitory activity. The majority of the compounds resulted to be active, with IC50 in the range 100 nM-50 μM.


Molecular model for sodium conductance and calcium transport in the squid axon.
A molecular and biochemically plausible model for the excitation process of the sodium pore is suggested. From basic arguments it is concluded that the sodium pore exists in at least three states: the resting state, the sodium conducting state, and the refractory state. They are connected to form a cyclic process. A specification of the different states is given. It is suggested that inactivation of the sodium pore results from a conformational change, which is caused by the transport of a calcium ion through the membrane. The transport carrier is the sodium pore. This assumption can explain the observed calcium influx during stimulation, and the effect of Ca on the rate of inactivation and on the rate, at which sodium conductance shuts off upon repolarization. It cannot give a quantitative explanation for the effect of Ca on the rate of rise, peak sodium conductance, and steady state inactivation. These asects are successfully described by the surface potential hypothesis, which has been published recently. It is concluded, that a combination of both theories gives a rather complete description of the sodium pore. The Ca transport model is discussed quantitatively and in great detail.


Modification by hexamethonium of the muscarinic receptors blocking activity of pancuronium and homatropine in isolated tissues of the guinea-pig.
In the guinea-pig left atrium, hexamethonium (C6) (0.1-3 mM) caused a parallel rightward shift of concentration-response curves for the negative inotropic response to carbachol (CCh) and oxotremorine (Oxo), the dose ratios obtained with the latter agonist being significantly greater than those for CCh at all concentrations of C6 investigated. In the presence of C6, the muscarinic receptor blocking activity of homatropine (20 microM) or of pancuronium (0.3-2.7 microM) appears to be reduced but if the effect of hexamethonium on concentration-response curves to the agonists is taken into consideration, the dose ratios produced by the combination of C6 with either homatropine or pancuronium were essentially as predicted for the combination of 2 competitive antagonists. The difference in the affinity of pancuronium for cardiac muscarinic receptors and ileal muscarinic receptors was also reduced in the presence of hexamethonium (0.3 mM).


Effectiveness of serious games in nurse education: A systematic review.
To systematically summarize research employing serious games in nurse education, to examine their effectiveness, to provide recommendations and implementation strategies, and to suggest future directions for the development and application of serious games in nurse education. A systematic review. An online search of the CINAHL, Medline, PubMed, EMBASE, PsycINFO, SCOPUS, and Web of Science databases, and a manual search of the reference lists of selected studies or review articles published in English and Korean between 1990 and July 2020. This systematic review was conducted in accordance with the Cochrane Handbook for Systematic Reviews of Interventions. Articles that employed a serious game approach in nurse education were included. Two authors independently screened and reviewed the articles and assessed the methodological quality using the Cochrane risk-of-bias tools. A total of seven studies met the inclusion criteria: three randomized controlled trials and four quasi-experimental studies. Heterogeneity was found across all studies regarding the application of serious games, platforms, and gamification elements. Most of the studies evaluated the effectiveness of serious games using knowledge tests, while two studies evaluated skills performance. Two randomized controlled trials and two one group before and after studies reported that the use of serious games improved nursing students' and nurses' knowledge and performance. This systematic review does not provide comprehensive insights into the effectiveness of serious games in nurse education. However, based on the evidence reviewed, we provide suggestions for developing and implementing serious games in nurse education to enhance students' knowledge and performance.


[Seasonal dynamics of adrenal 11-hydroxycorticosteroid secretion in Citellus erythrogenus susliks].
It has been demonstrated that during different periods of life cycle of the ground squirrels their adrenals produce various amounts of glucocorticoids. Maximum secretion of 11-oxycorticosteroids by the adrenals was noted in active period of animals (May), decreasing to the period of preparation to hibernation (August). During hibernation of the animals, 11-oxycorticosteroid secretion exhibits intrinsic endogenous rhythm. Whereas the first half of hibernation is characterized by a constant secretion (October, November, December), during the second one (from January till March) the secretion of 11-oxycorticosteroids by the adrenals increases.


Postactivation potentiation of dynamic conditioning contractions on rowing sprint performance.
This study examined the post-activation potentiation effects of maximal dynamic contractions and gender on rowing sprint ability. Repeated measures. Thirty-four male (n=17) and female (n=17) university students with experience in rowing took part in this study conducted across three weeks. Following familiarisation of the 10-second maximal rowing performance test on a rowing ergometer during Week 1, participants were randomly allocated to either complete a control or experimental session during Week 2 and 3. One rowing performance test was conducted during the control session whilst two rowing performance tests were conducted during the experimental session separated by 6-min. The first rowing performance test during the experimental session was used to: (1) compare measures with the control session to assess day-to-day repeatability; and (2) induce post-activation potentiation effects for the second rowing performance test. Based on effect size calculations, results showed moderate-large increases for average power output (+2.5%), peak power output (+1.5%) and power output during first stroke (+0.79%). Maximal dynamic contractions on a rowing ergometer improved subsequent rowing sprint ability in recreationally experienced male and female rowers. Accordingly, dynamic conditioning contractions on a rowing ergometer may enhance subsequent sprint-start for rowing competition success.


Systemic Risk Factors for Vitreous Hemorrhage Secondary to Polypoidal Choroidal Vasculopathy.
It remains unclear whether systemic factors are associated with an increased risk of vitreous hemorrhage (VH) secondary to polypoidal choroidal vasculopathy (PCV), and there is no method to predict the possibility of VH occurrence in patients with PCV. This study aimed to investigate and visualize systemic risk factors for VH in patients with PCV. Data on the sex, age, history of systematic diseases, best-corrected visual acuity, intraocular pressure, and laboratory data of patients with PCV were collected from the medical record system. Univariate and multivariate binary logistic regression analyses were applied to investigate independent risk factors for VH in patients with PCV. Receiver operating characteristic analysis and nomograms were used to visualize the independent risk factors. The patient population comprised 115 patients with VH secondary to PCV and 181 patients with PCV without VH. Binary logistic regression analyses showed that higher white blood cell count [WBC; odds ratios (OR) 1.247], higher aspartate aminotransferase/alanine aminotransferase ratio (AST/ALT; OR 2.339), and longer activated partial thromboplastin time (APTT; OR 1.196) were independent risk factors of VH in patients with PCV. Integrated application of APTT, AST/ALT, and WBC as markers showed the best performance for distinguishing patients with VH, with an area under the curve of 0.723. The nomogram was created for doctors to calculate the possibility of VH in a patient with PCV. Higher WBC, higher AST/ALT, and longer APTT are independent serum risk factors of VH secondary to PCV, which may shed light on VH prevention in patients with PCV.


Detection and genetic characterization of enteric viruses in diarrhoea outbreaks from swine farms in Spain.
The aim of this work was to study the prevalence and distribution of Porcine astrovirus (PAstV), Porcine kobuvirus (PKoV), Porcine torovirus (PToV), Mammalian orthoreovirus (MRV) and Porcine mastadenovirus (PAdV) as well as their association with widely recognized virus that cause diarrhoea in swine such as coronavirus (CoVs) and rotavirus (RVs) in diarrhoea outbreaks from Spanish swine farms. Furthermore, a selection of the viral strains was genetically characterized. PAstV, PKoV, PToV, MRV and PAdV were frequently detected. Particularly, PAstV and PKoV were detected in almost 50% and 30% of the investigated farms, respectively, with an age-dependent distribution; PAstV was mainly detected in postweaning and fattening pigs, while PKoV was more frequent in sucking piglets. Viral co-infections were detected in almost half of the outbreaks, combining CoVs, RVs and the viruses studied, with a maximum of 5 different viral species reported in three investigated farms. Using a next generation sequencing approach, we obtained a total of 24 ARN viral genomes (> 90% genome sequence), characterizing for first time the full genome of circulating strains of PAstV2, PAstV4, PAstV5 and PToV on Spanish farms. Phylogenetic analyses showed that PAstV, PKoV and PToV from Spanish swine farms clustered together with isolates of the same viral species from neighboring pig producing countries. Although further studies to evaluate the role of these enteric viruses in diarrhoea outbreaks are required, their wide distribution and frequent association in co-infections cannot be disregard. Hence, their inclusion into routine diagnostic panels for diarrhoea in swine should be considered.


[Diseases and diagnosis of the biliary system : When does the gastroenterologist need the radiologist?]
Biliary diseases require fast and rational use of diagnostic tests by both gastroenterologists and radiologists. Standard diagnostic workup includes transabdominal ultrasound, endoscopic retrograde cholangiography (ERC), endoscopic ultrasound, direct cholangioscopy, magnetic resonance cholangiopancreatography (MRI/MRCP), and computed tomography (CT). Modular cholangioscopy is a novel diagnostic method. The goal of diagnostic examinations is the determination of the location of obstructions and differentiation of benign from malignant lesions. Transabdominal ultrasound is risk-free and can show the gallbladder in great detail providing high diagnostic accuracy in most conditions. Endoscopic ultrasound, ERC and/or cholangioscopy are powerful tools to investigate the large bile ducts but are associated with inherent procedural risks. Gall bladder diseases can often be diagnosed with transabdominal ultrasound alone. Bile duct disease often requires the use of endoscopic ultrasound, ERC and/or cholangioscopy.


The prevention of transfusion-associated circulatory overload.
Transfusion-associated circulatory overload (TACO) is an important and potentially injurious complication of transfusion that is underappreciated by clinicians. Risk factors for TACO include being at an extreme of age, having preexisting cardiac and/or (potentially) renal dysfunction, acute myocardial infarction, and individuals receiving plasma. Keys to preventing TACO, aside from identifying high-risk individuals, should be multifaceted. We advocate for the widespread use of pretransfusion checklists and implementation of nonemergent transfusion protocols. We suggest the regular use of pretransfusion diuretics in high-risk individuals. When a transfusion is required, we believe that "critical" nursing supervision and leadership are instrumental in the coordination of slow transfusion rates on computerized infusion pumps and ensuring patients are appropriately monitored. We believe that using these methodologies on a global scale will prevent many TACO events and minimize the severity when it does occur.


Transcervical double mandibular osteotomy approach to the infratemporal fossa.
In this study, we propose an alternative to the traditional transmandibular lower lip and chin splitting approach for exposing high infratemporal fossa and parapharyngeal space lesions involving the carotid canal and jugular foramen. We present 2 cases of high skull base tumors removed transcervically with anterior and posterior segmental mandibulotomies preserving the mental nerve without the use of a lip or chin incision. Making the posterior osteotomy in an inverted L configuration is necessary so that the coronoid process does not prevent rotation of the mandible out of the visual field. Both patients had complete tumor resection with access to the carotid canal and jugular foramen and functional preservation of the mental nerve and marginal branch of the facial nerve. Neither patient had malocclusion or other dental complications from the approach. This novel technique is useful for providing excellent access to high infratemporal fossa or parapharyngeal space tumors. It avoids the traditional chin or lip incision and preserves the mental and facial nerves and is a useful procedure in the armamentarium of skull base/cerebrovascular neurosurgeons.


Systemic review and network meta-analysis comparing minimal surgical techniques for rectal cancer: quality of total mesorectum excision, pathological, surgical, and oncological outcomes.
Minimal invasive surgery has revolutionized recovery in rectal cancer patients. However, there has been debate on its effect on quality of total mesorectal excision (TME) and oncological outcomes. This network meta-analysis compares laparoscopic, robotic-assisted, and transanal TMEs. This study shows that All three surgical techniques are comparable across TME quality and oncological outcomes. Ultimately, good outcomes are based on each individual surgeon choosing an approach based on their expertise.


The application of supported liquid extraction in the analysis of benzodiazepines using surface enhanced Raman spectroscopy.
Benzodiazepines are among the most frequently prescribed medicines for anxiety disorders and are present in many toxicological screens. These drugs are often administered in the commission of drug facilitated sexual assaults due their effects on the central nervous system. Due to the potency of the drugs, only small amounts are usually given to victims; therefore, the target detection limit for these compounds in biological samples has been set at 50 ng/mL. Currently the standard screening method for detection of this class of drug is the immunoassay; however, screening methods that are more sensitive and selective than immunoassays are needed to encompass the wide range of structural variants of this class of compounds. Surface enhanced Raman spectroscopy (SERS) can be highly sensitive and has been shown to permit analysis of various benzodiazepines with limits of detection as low as 6 ng/mL. This technique permits analytical results in less than 2 min when used on pure drug samples. For biological samples, a key issue for analysis by SERS is removal of exogenous salts and matrix components. In this paper we examine supported liquid extraction as a useful preparation technique for SERS detection. Supported liquid extraction has many of the benefits of liquid-liquid extraction along with the ability to be automated. This technique provides a fast and clean extraction for benzodiazepines from urine at a pH of 5.0, and does not produce large quantities of solvent waste. To validate this procedure we have determined figures of merit and examined simulated urine samples prepared with commonly appearing interferences. It was shown that at a pH 5.0 many drugs that are prevalent in urine samples can be removed, permitting a selective detection of the benzodiazepine of interest. This technique has been shown to provide rapid (less than 20 min), sensitive, and specific detection of benzodiazepines with limits of detection between 32 and 600 ng/mL and dynamic range of 32-25,000 ng/mL. It provides the forensic community with a sensitive and specific screening technique for the detection of benzodiazepines in drug facilitated assault cases.


[The control of solid waste with the participation of a low-income population].
Two studies were undertaken with a view to improving the health conditions of a shanty town area in the city of S. Paulo, Brazil. The objective was to modify littering behavior and to implement litter-control procedures with the participation of the inhabitants. Results demonstrated the adequacy of the procedures adopted and suggest a possible contribution on the part of psychology to public health.


Cancer-related mRNA expression analysis using a novel flow cytometry-based assay.
Cancer-related gene expression data mostly originate from unfractionated bulk samples, leading to "expression averaging" of heterogeneous populations. Multicolor flow cytometry (FCM) may distinguish heterogeneous populations based on the phenotypic characterization of single-cells, but is not applicable for RNA targets. Here, we evaluated the PrimeFlow™ RNA assay, a novel FCM-based assay designed to measure gene expressions, in two cancer entities with high and low RNA target levels. Neuroblastoma (NB) cell lines were studied for MYCN gene expression by PrimeFlow™ and compared with the gold standard, RT-qPCR. Dilution series of NB cells (0.10-11%) were prepared to evaluate performance in small cell populations. Diagnostic material of de novo acute myeloid leukemia (AML) patients was used to measure Wilms' tumor 1 (WT1) expression in bulk leukemic cells and rare subsets, e.g. leukemic stem cells (LSCs). FCM analysis was performed on a FACSCanto II (BD Biosciences) using Infinicyt™ (Cytognos® ) for data analysis. mRNA expression was reported by normalized mean fluorescence intensity (MFI) values and staining indices. MYCN mRNA quantified by PrimeFlow™ significantly correlated with RT-qPCR and remained detectable in small (0.1%) populations. Using PrimeFlowTM , WT1 levels were shown to be significantly higher in AML patient samples with WT1 overexpression, previously defined by RT-qPCR. Moreover, WT1 overexpression was distinguishable between heterogeneous cell populations and remained measurable in rare LSCs. PrimeFlow™ is a sensitive technique to investigate mRNA expressions, with high concordance to RT-qPCR. High (MYCN) and subtle (WT1) overexpressed mRNA targets can be quantified in heterogeneous and rare subpopulations e.g. LSCs. © 2017 International Clinical Cytometry Society.


Bacterial overgrowth, dysbiosis, inflammation, and dysmotility in the Cystic Fibrosis intestine.
Gastrointestinal disease in Cystic Fibrosis (CF) is caused by defective chloride and bicarbonate transport in intestinal cells leading to reduced intraluminal fluidity, increased mucous viscosity and consequently development of intestinal inflammation, dysbiosis and often times dysmotility. This triad is also referred to as the "CF gut". A diagnosis is mainly based on clinical observation and treatment is often times decided empirically. This review of the literature should provide CF caregivers with some tools to identify intestinal inflammation, dysbiosis and dysmotility as possible cause for their patient's gastrointestinal complaints and provide an overview of our current approach to its management.


Identification of a functional epitope of the Nogo receptor by a combinatorial approach using ribosome display.
The Nogo receptor (NgR) plays a central role in mediating growth-inhibitory activities of myelin-derived proteins, thereby severely limiting axonal regeneration after injury of the adult mammalian central nervous system (CNS). The inhibitory proteins Nogo, myelin-associated glycoprotein (MAG) and oligodendrocyte myelin glycoprotein (OMgp) all bind to the extracellular leucine-rich repeat (LRR) domain of NgR, which provides a large molecular surface for protein-protein interactions. However, epitopes within the LRR domain of NgR for binding Nogo, MAG and OMgp have not yet been revealed. Here, we report an evolutionary approach based on the ribosome display technology for detecting regions involved in ligand binding. By applying this method of "affinity fingerprinting" to the NgR ligand binding domain we were able to detect a distinct region important for binding to Nogo. Several residues defining the structural epitope of NgR involved in interaction with Nogo were subsequently confirmed by alanine scanning mutagenesis.


The significance of entry routes as point and non-point sources of pesticides in small streams.
In an agricultural catchment area in Germany we analyzed water samples from five entry routes for 2 insecticides. 5 fungicides and 13 herbicides. The sewage plant outlet and the emergency overflow of a sewage sewer contained only herbicides. In each farmyard runoff we found on average 24 g pesticides during application period, presumably caused by cleaning the spraying equipment. In comparison, the field runoff and the rainwater sewer contained less load, but also insecticides, fungicides and herbicides. The sewage plant caused 65.9% of the total herbicide load, the sewage sewer 19.8% and the farmyard runoff 12.8%. The farmyards also caused 83.7% of total insecticide and 83.8% of fungicide load. The total load of all entry routes is correlated with the amount of pesticides applied in the catchment area and the Ko/w value for each pesticide (mult. regress. r2: 0.82; p<0.0001; n = 14). In stream A the sewage plant caused a slight but continuous contamination by herbicides with 82% of the total load found during low-water phases. In comparison, stream B had only farmyard runoff and non-point sources, which caused high peaks of herbicide and a contamination by insecticides. Consequently, high-water phases generated 70% of the total pesticide load.


Selective decontamination of subglottic area in mechanically ventilated patients with multiple trauma.
To determine whether selective decontamination locally in the subglottic area (SDSA) reduces tracheal colonization and prevents ventilator-associated pneumonia (VAP) in patients with multiple trauma. A prospective randomized, controlled, clinical study in a 14-bed general intensive care unit of a university hospital. 79 consecutive multiple trauma patients admitted to the ICU who were expected to be mechanically ventilated for more than 5 days; 61 patients completed the protocol. Patients were randomly assigned to receive SDSA using a continuous infusion of a suspension containing three nonabsorbable antibiotics (polymyxin, tombramycin, and amphotericin B; n=30) or placebo ( n=31). The incidence of bronchial and gastric colonization and the number of cases of VAP were recorded. Gastric fluid and tracheal secretion cultures were obtained soon after intubation and thereafter every 4 days. Etiological diagnosis of VAP was based on samples taken by a specific protected double catheter set. VAP developed in 5 of 30 (16.6%) patients receiving SDSA and 16 of 31 (51.6%) patients receiving placebo. Negative bronchial secretion cultures were found in 14 of 30 (46.6%) patients in the SDSA group and in only 3 of 31 (9.6%) patients in the control group. No patient with negative bronchial secretion culture developed VAP. No significant differences in outcome were found. The SDSA is an effective and safe type of chemoprophylaxis against tracheal colonization and can significantly reduce the incidence of VAP in mechanically ventilated patients with multiple trauma.


P-glycoprotein inserted in planar lipid bilayers formed by liposomes opened on amorphous carbon and Langmuir-Blodgett monolayer.
The insertion of proteins into planar lipid layers is of outstanding interest as the resulting films are suitable for the investigation of protein structure and aggregation in a lipid environment and/or the development of biotechnological applications as biosensors. In this study, purified P-glycoprotein (P-gp), a membrane drug pump, was incorporated in model membranes deposited on solid supports according to the method by Puu and Gustafson, Biochim. Biophys. Acta 1327 (1997) 149-161. The models were formed by a double lipid layer obtained by opening P-gp-containing liposomes onto two hydrophobic supports: amorphous carbon films and Langmuir-Blodgett (L-B) lipid monolayers, which were then observed by transmission electron microscopy and atomic force microscopy, respectively. Before the opening of liposomes, the P-gp structure and functionality were verified by circular dichroism spectroscopy and enzymatic assay. Our micrographs showed that liposomes containing P-gp fuse to the substrates more easily than plain liposomes, which keep their rounded shape. This suggests that the protein plays an essential role in the fusion of liposomes. To localize P-gp, the immunogold labeling of two externally exposed protein epitopes was carried out. Both imaging techniques confirmed that P-gp was successfully incorporated in the model membranes and that the two epitopes preserved the reactivity with specific mAbs, after sample preparation. Model membranes obtained on L-B monolayer incorporated few molecules with respect to those incorporated in the model membrane deposited onto amorphous carbon, probably because of the different mechanism of proteoliposome opening. Finally, all particles appeared as isolated units, suggesting that P-gp molecules were present as monomers.


Comparison of two different methods of quantitative coronary angiography in patients with acute coronary syndromes.
The minimal cost algorithm (MCA) commonly used for quantitative coronary arteriography has limitations in definition of complex lesion morphology. A gradient field transform (GFT) algorithm has been designed for the better analysis of complex lesions. We compared MCA with GFT in angiograms of 125 patients in the Myocardial Infarction with Novastan and t-PA (MINT) trial. Lesion border definition was rated as one (poor), two (good), or three (very good). While MCA- and GFT-derived reference diameters (RDs) were similar, GFT yielded smaller minimal lumen diameter (MLD) than MCA by 0.22 +/- 0.31 mm (P < 0.01), and the difference between GFT- and MCA-derived MLDs increased with decreasing MLD. Mean percent diameter stenosis (% DS) was 9.1% +/- 11.1% greater by GFT (P < 0.001). Lesion border definition in simple lesions was similar (not significantly different). However, in complex lesions GFT performed better (2.49 +/- 0.61 vs. 2.11 +/- 0.74; P < 0.05). Thus, GFT appears to improve analysis of complex lesions compared to MCA. GFTs role in angiographic trials and clinical practice deserves further study.


In vitro characterization and inhibition of the interaction between ciprofloxacin and berberine against multidrug-resistant Klebsiella pneumoniae.
Ciprofloxacin is a quinolone antibiotic used to treat Klebsiella pneumoniae infections in the clinic. Previous studies have demonstrated that berberine exhibits antibacterial activity and less acquired resistance related to efflux pumps. The multidrug efflux pump acrAB-tolC can be stimulated to expel as much toxic material as possible from the cells, but a detrimental effect can be produced owing to an overcrowded periplasm with excess expression products, which inhibits bacterial growth. In this study, the in vitro antibacterial activities of ciprofloxacin in combination with berberine were evaluated and compared with those of ciprofloxacin and berberine alone by evaluating the MIC, MBC and summation fractional IC against 20 clinical multidrug-resistant K. pneumoniae isolates, 1 quality control bacterium and 1 induced-resistance bacterium. Susceptibility tests showed that the MIC for the combination of berberine and ciprofloxacin was 1/2 that of the individual agents or less. Antimicrobial activities of 18.18% synergy and 77.27% additivity were found. Furthermore, synergism was verified through a time-kill assay, which suggested that the synergistic antibacterial effect of the two-drug combination may, to some extent, be related to the high expression of the acrAB-tolC and acrR multidrug efflux pumps. Indeed, the expression of these genes was increased >14-fold in the isolates affected by ciprofloxacin-berberine combination synergism.


Long-term treatment of blepharospasm with botulinum toxin A: a service-based study over a 16-year follow-up in southern China.
To elucidate the effect of long-term treatment with botulinum toxin A (BTX-A) for blepharospasm. Prevalence data and clinical features in southern China and influencing factors for selecting BTX-A treatment were explored. We collected data retrospectively from 338 consecutive patients diagnosed with blepharospasm over 16 years to assess prevalence data and clinical features. Thereafter, all patients were classified into BTX-A (n = 135) or non-BTX-A (n = 203) treatment groups according to the patients' requests in order to explore the factors influencing whether BTX-A treatment was chosen. Furthermore, dynamic follow-up data were analyzed to evaluate the long-term efficacy in the BTX-A group. The prevalence was 23.3 per million, with an onset age of 50.3 ± 12.3 years and a female:male ratio of 2.4:1; the most common symptom was excessive blinking (91.2%). The symptom severity and psychological assessment scores were significantly decreased by treatment with BTX-A (p < 0.01), and there was no significant difference in response duration with the prolongation of BTX-A injections. Adverse events occurred 52 times (5.0%) among 1038 injections. The symptom severity and psychological assessment scores and the occurrence of eye-opening difficulty were higher, and medical expenses and the symptom tolerability rate were lower in the BTX-A group than in the non-BTX-A group (p < 0.05). The onset age was earlier than that in Western countries. However, starting BTX-A treatment early is justified, even though a higher dosage was needed to maintain reliable long-term efficacy. Additionally, symptom severity and medical expenses are the primary factors affecting whether patients select BTX-A treatment.


Smoking dependence and anxio-depressive disorders in Tunisian smokers attending the smoking cessation clinic in a university hospital.
Smokers with comorbid anxio-depressive disorders are more prone to progress to a more severe level of dependence and to experience more severe nicotine withdrawal symptoms than smokers without anxio-depressive disorders. To determine the relationship between tobacco dependence and anxio-depressive disorders as well as assessing their impact on the withdrawal. We conducted a cross-sectional study among attendees of the smoking cessation clinic of Sahloul University Hospital, Sousse, Tunisia, from December 2009 to May 2015. The monitoring of the attendees was performed through retrieving the records until May 2016 in order to verify their smoking cessation status at 1 year. Overall, 534 smokers were included. We identified 315 smokers (59%) presenting an anxio-depressive disorder. Based on the HAD scale, we found 231 patients (43.4%) with anxiety disorders, 200 (37.6%) patients with depressive disorders, and 116 (21.8%) patients with anxio-depressive disorder. In multivariate analysis, only a high number of consultation was associated with a better rate of tobacco cessation at 6 months. However, no factor was found linked to the relapse at 1 year. According to our results, only a high number of consultation was revealed as an independent factor of withdrawal for anxio-depressed smokers. It is necessary to simultaneously use the nicotinic substitutions and anxio-depressive treatment to ensure the tobacco cessation.


Low-dose telomerase is required for the expansion and migration of placental mesenchymal stem cells.
Telomerase is activated in pluripotent stem cells and the majority of tumors and is postulated to be necessary for the acquisition of self-renewal and long-term proliferation. Placental mesenchymal stem cells (PMSCs) are very promising in regenerative medicine owing to their great capacity for self-renewal and differentiation potential. Although telomerase activity in the placenta is naturally low, it remains unclear whether telomerase activity is required for the properties of PMSCs. We herein isolated and identified a PMSC line carrying compound heterozygote variations in hTERT (DC-PMSCs) that lost telomerase activity, showed a typical surface phenotype of MSCs, and was able to differentiate into multiple cell lineages. DC-PMSCs showed accelerated telomere erosion, advanced senescence, and diminished migratory and invasive capabilities. RNA-seq identified 361 differentially expressed genes between DC-PMSCs and control groups, most of which were enriched in extracellular matrix, ECM, and related pathways. Knockdown of telomerase subunit genes in PMSCs confirmed the phenotype and attenuated the expression of extracellular matrix components and matrix metalloproteases. Our results suggest that low telomerase activity is not essential for the properties of MSCs, but that it is required for community maintenance and for the migration of PMSCs.


Vagal Nerve Stimulation: The Effect on the Brain Oscillatory Field Potential.
More than thirty years of medical treatment with the use of vagal nerve stimulation (VNS) has shown that this therapeutic procedure works in a number of homeostatic disturbances. Although the clinical usage of VNS has a long history, our knowledge about the central mechanisms underlying this treatment is still limited. In the present paper we review the effects of VNS on brain oscillations as a possible electrophysiological bio-marker of VNS efficacy. The review was prepared mainly on the basis of data delivered from clinical observations and the outcomes of electrophysiological experiments conducted on laboratory animals that are available in PubMed. We consciously did not focus on epileptiform activity understood as a pathologic oscillatory activity, which was widely discussed in the numerous previously published reviews. The main conclusion of the present paper is that further, well-designed experiments on laboratory animals are absolutely necessary to address the electrophysiological issues. These will fill a number of gaps in our present knowledge of the central mechanisms underlying VNS therapy.


Prediction of individual graft for anterior cruciate ligament reconstruction using anthropometric data.
Multiple options for individual anterior cruciate ligament (ACL) reconstruction exist; still, there are no guidelines for the preoperative preparation. The aim of this study was to assess the correlation between patients' anthropometric data (height, weight, and age) and measurements of potential tendons (quadriceps-, patella, hamstrings tendon) for an anterior cruciate ligament reconstruction. MR images of 102 patients have been analyzed. Measurements of the ACL were performed with respect to its length and angle. The diameter and length as well as width of the quadriceps and patella tendon, the cross-sectional area (CSA) and diameter of the hamstring tendons have been assessed. Patients' height, weight, BMI, sex and age have been recorded. The correlations of these measurements with the patients' anthropometric data have been calculated. Inter-rater and intra-rater reliability based on intra-class correlation (ICC) was evaluated. The mean lengths of the ACL were 29.8 ± 3.5 mm, tibial insertion sites 15.8 ± 2.5 mm and femoral insertion sites 15.2 ± 3.0 mm. Thickness of the quadriceps tendons was 4.7 ± 1.1 mm and patella tendon 3.2 ± 0.7 mm. The patients' height showed significant positive correlations with the CSA of the hamstring tendon measurements, the length of the ACL, and the insertion sites of the ACL. Patients' weight showed significant positive correlations with patella tendon thickness, the CSA of the hamstring tendons, the length of the ACL, and the tibial and femoral insertion sites. Patients' age showed a significant positive correlation with patella tendon thickness. The ICCs for intra- and inter-rater reliability were 0.98 (95% CI 0.95-0.99, p < 0.001) and 0.94 (95% CI 0.88-0.99, p < 0.001). Anthropometric data with respect to height, weight, and sex can help to predict the dimension of tendons for ACL reconstruction and do correlate with ACL tendon. Patients at risk for small graft dimensions and failure are younger than 20 years and physically active. MRIs of patients at risk for small graft dimensions should be analyzed on tendon length and cross section areas preoperatively to determine the appropriate tendon harvest and fixation technique.


Spindle assembly checkpoint and centrosome abnormalities in oral cancer.
Like many solid tumours, oral squamous cell carcinomas (OSCC) invariably exhibit chromosomal instability (CIN) leading to aneuploidy. The mechanisms responsible for CIN in OSCC, however, are largely unknown. This study examined the fidelity of the spindle checkpoint, together with the number, structure and function of centrosomes in a series of well-characterised aneuploid immortal OSCC-derived cell lines that harbour p53 and p16(INK4A) defects. The spindle checkpoints were fully functional in 2 of 7 cell lines and attenuated in the remaining 5 cell lines. Overexpression of the spindle checkpoint protein, Cdc20, was observed in 2 of the cell lines with attenuated checkpoints. Defects in centrosome number, size and localisation were detected in 5 of the cell lines. Clonal cell populations contained cells with both normal and abnormal numbers of centrosomes, suggesting that the control of centrosome number may be inherently unstable in OSCC-derived cell lines. Centrosomal abnormalities were then examined in tissue samples of oral epithelial dysplasias and carcinomas. Abnormal centrosomes were detected in all the tissues examined albeit in a low percentage of cells (<1% to >5%). The percentage of cells containing centrosome abnormalities was significantly higher in the carcinomas than in the dysplasias (p<0.02) and in the poorly differentiated SCCs relative to their moderately differentiated (p<0.04) and well-differentiated (p<0.01) counterparts. We suggest that the genetic alterations associated with the development of the immortal phenotype, together with spindle checkpoint and centrosome defects, are responsible, albeit in part, for the complex karyotypes observed in OSCC. The presence of centrosome abnormalities in oral dysplasias raises the possibility that such defects might contribute to malignant progression.


Sensory profiles obtained from parental reports correlate with independent assessments of development in very preterm children at 2 years of age.
Very preterm (VPT) children have different sensory profiles than term-born controls, but how the sensory profiles in VPT children relate to development has not been reported. The aim of this study was to examine the relationship between VPT infant sensory profiles and concurrent developmental outcomes at 2 years' corrected age. Cohort study. 243 children <30 weeks' gestation. Primary caregivers completed the Infant/Toddler Sensory Profile Questionnaire to obtain information on sensory processing at 2 years of age. Independent observers assessed the child's neurodevelopment with either the Mental Developmental Index (MDI) and Psychomotor Developmental Index (PDI) of the Bayley Scales of Infant Development version 2 (Bayley 2) or the Cognition, Language and Motor Composites of the Bayley Scales of Infant and Toddler Development version 3 (Bayley 3). A stronger Low Registration pattern correlated with lower MDI and PDI scores and a stronger Sensation Avoiding pattern correlated with a lower PDI score. A stronger Low Registration pattern correlated with a lower Language Composite score. More frequent visual and oral sensory processing behaviours were associated with higher performance on the MDI and PDI, with more frequent auditory sensory processing behaviours also associated with higher PDI scores. More frequent auditory, touch and oral sensory processing behaviours were associated with improved outcomes on the Language Composite and more frequent auditory, touch and vestibular processing behaviours correlated with improved outcomes on the Cognition Composite. A secondary analysis using a computed MDI score derived from the Bayley 3 scores did not substantially alter any conclusions. Different sensory profile patterns obtained from parental reports of VPT children are associated with various aspects of neurodevelopment at 2 years of age, obtained from independent assessment.


Machine Learning-Based Prognostic Model for Patients After Lung Transplantation.
Although numerous prognostic factors have been found for patients after lung transplantation (LTx) over the years, an accurate prognostic tool for LTx recipients remains unavailable. To develop and validate a prognostic model for predicting overall survival in patients after LTx using random survival forests (RSF), a machine learning algorithm. This retrospective prognostic study included patients who underwent LTx between January 2017 and December 2020. The LTx recipients were randomly assigned to training and test sets in accordance with a ratio of 7:3. Feature selection was performed using variable importance with bootstrapping resampling. The prognostic model was fitted using the RSF algorithm, and a Cox regression model was set as a benchmark. The integrated area under the curve (iAUC) and integrated Brier score (iBS) were applied to assess model performance in the test set. Data were analyzed from January 2017 to December 2019. Overall survival in patients after LTx. A total of 504 patients were eligible for this study, consisting of 353 patients in the training set (mean [SD] age, 55.03 [12.78] years; 235 [66.6%] male patients) and 151 patients in the test set (mean [SD] age, 56.79 [10.95] years; 99 [65.6%] male patients). According to the variable importance of each factor, 16 were selected for the final RSF model, and postoperative extracorporeal membrane oxygenation time was identified as the most valuable factor. The RSF model had excellent performance with an iAUC of 0.879 (95% CI, 0.832-0.921) and an iBS of 0.130 (95% CI, 0.106-0.154). The Cox regression model fitted by the same modeling factors to the RSF model was significantly inferior to the RSF model with an iAUC of 0.658 (95% CI, 0.572-0.747; P < .001) and an iBS of 0.205 (95% CI, 0.176-0.233; P < .001). According to the RSF model predictions, the patients after LTx were stratified into 2 prognostic groups displaying significant difference, with mean overall survival of 52.91 months (95% CI, 48.51-57.32) and 14.83 months (95% CI, 9.44-20.22; log-rank P < .001), respectively. In this prognostic study, the findings first demonstrated that RSF could provide more accurate overall survival prediction and remarkable prognostic stratification than the Cox regression model for patients after LTx.


FIRM: Flexible integration of single-cell RNA-sequencing data for large-scale multi-tissue cell atlas datasets.
Single-cell RNA-sequencing (scRNA-seq) is being used extensively to measure the mRNA expression of individual cells from deconstructed tissues, organs and even entire organisms to generate cell atlas references, leading to discoveries of novel cell types and deeper insight into biological trajectories. These massive datasets are usually collected from many samples using different scRNA-seq technology platforms, including the popular SMART-Seq2 (SS2) and 10X platforms. Inherent heterogeneities between platforms, tissues and other batch effects make scRNA-seq data difficult to compare and integrate, especially in large-scale cell atlas efforts; yet, accurate integration is essential for gaining deeper insights into cell biology. We present FIRM, a re-scaling algorithm which accounts for the effects of cell type compositions, and achieve accurate integration of scRNA-seq datasets across multiple tissue types, platforms and experimental batches. Compared with existing state-of-the-art integration methods, FIRM provides accurate mixing of shared cell type identities and superior preservation of original structure without overcorrection, generating robust integrated datasets for downstream exploration and analysis. FIRM is also a facile way to transfer cell type labels and annotations from one dataset to another, making it a reliable and versatile tool for scRNA-seq analysis, especially for cell atlas data integration.


Illicit stimulant use in a United States heart failure population presenting to the emergency department (from the Acute Decompensated Heart Failure National Registry Emergency Module).
Illicit stimulant drug use may have a profound clinical impact in acute decompensated heart failure (ADHF). The chronic use of cocaine and methamphetamine may lead to overt cardiomyopathy and ADHF. The Acute Decompensated Heart Failure National Registry Emergency Module (ADHERE-EM) collected data on patients presenting to emergency departments with ADHF at 83 geographically dispersed hospitals in the United States. This registry was queried to determine the rate of self-reported illicit drug use in emergency department patients presenting with ADHF and compare these patients with those without illicit drug use. The registry enrolled 11,258 patients with ADHF with drug use data from January 2004 to March 2006. Of these patients, 594 (5.3%) self-reported current or past stimulant drug use. Compared with nonusers, these patients were more likely to be younger (median age 49.7 vs 76.1 years), to be African American (odds ratio 11.9, 95% confidence interval 9.8 to 14.4), and to have left ventricular ejection fractions <40% (odds ratio 3.4, 95% confidence interval 2.8 to 4.2). Admitted users had no difference in mortality (adjusted odds ratio 0.83, 95% confidence interval 0.25 to 2.72) compared with nonusers. In conclusion, data from ADHERE-EM suggest that a clinically important percentage of patients with ADHF report the use of illicit stimulant drugs. Although these patients are younger with a greater degree of LV dysfunction, they did not have greater risk-adjusted mortality.


Recovering incomplete data using Statistical Multiple Imputations (SMI): a case study in environmental chemistry.
This paper presents a statistical technique that can be applied to environmental chemistry data where missing values and limit of detection levels prevent the application of statistics. A working example is taken from an environmental leaching study that was set up to determine if there were significant differences in levels of leached arsenic (As), chromium (Cr) and copper (Cu) between lysimeters containing preservative treated wood waste and those containing untreated wood. Fourteen lysimeters were setup and left in natural conditions for 21 weeks. The resultant leachate was analysed by ICP-OES to determine the As, Cr and Cu concentrations. However, due to the variation inherent in each lysimeter combined with the limits of detection offered by ICP-OES, the collected quantitative data was somewhat incomplete. Initial data analysis was hampered by the number of 'missing values' in the data. To recover the dataset, the statistical tool of Statistical Multiple Imputation (SMI) was applied, and the data was re-analysed successfully. It was demonstrated that using SMI did not affect the variance in the data, but facilitated analysis of the complete dataset.


A cluster of 3' coterminal transcripts from US12-US17 locus of human cytomegalovirus.
Among all the human cytomegalovirus (HCMV) gene families, US12 family is relatively undefined in their transcriptional profile and biological functions. In this study, the transcription pattern and characteristics of HCMV US12-US17 gene region were studied extensively. Twenty-three clones harboring US12 cDNA sequence were screened out from a late cDNA library of an HCMV clinical isolate, Han. Using a set of US12-US17 gene-specific probes, six transcripts from US12-US17 locus were detected by northern blot at late kinetics of the clinical isolate. One additional transcript was found in late RNA of HCMV strain AD169. No evidence showing these transcripts contain introns by reverse transcription PCR. 3' and 5' termini of these transcripts were confirmed by Rapid Amplification of cDNA Ends. A novel protein-coding region was predicted in the shorter US14 transcript with an alternative in-frame 5' translation initiation site compared to that of the previously predicted US14 ORF. Our findings demonstrate the existence of a cluster of 3' coterminal unspliced transcripts with distinct 5' transcriptional initiation sites originated from US12-US17 gene region in the late infection phase of an HCMV clinical strain.


Differential diagnosis of pseudodementia in the elderly.
When depression occurs in the elderly, it may mimic dementia. The identification of depressive pseudodementia is important because this syndrome, unlike true dementia, often responds to antidepressant treatment. In this paper, the authors present strategies for differentiating pseudodementia, dementia, and coexisting depression and dementia. The treatment of depression in the elderly is also discussed.


Prevalence and predictors of unintended pregnancy among women: an analysis of the Canadian Maternity Experiences Survey.
Unintended pregnancies (mistimed or unwanted during the time of conception) can result in adverse outcomes both to the mother and to her newborn. Further research on identifying the characteristics of unintended pregnant women who are at risk is warranted. The present study aims to examine the prevalence and predictors of unintended pregnancy among Canadian women. The analysis was based on the 2006 Maternity Experiences Survey targeting women who were at least 15 years of age and who had a singleton live birth, between February 15, 2006 to May 15, 2006 in the Canadian provinces and November 1, 2005 to February 1, 2006 for women in the Canadian territories. The primary outcome was the mother's pregnancy intention, where unintended pregnancy was defined as women who wanted to become pregnant later or not at all. Sociodemographic, maternal and pregnancy related variables were considered for a multivariable logistic regression. Adjusted Odds Ratios (OR) and 95% Confidence Intervals (95% CI) were reported. Overall, the prevalence of unintended pregnancy among Canadian women was 27%. The odds of experiencing an unintended pregnancy were statistically significantly increased if the mother was: under 20 years of age, immigrated to Canada, had an equivalent of a high school education or less, no partner, experienced violence or abuse and had 1 or more previous pregnancies. Additionally, mothers who reported smoking, drinking alcohol and using drugs prior to becoming pregnant, were all associated with an increased likelihood of experiencing an unintended pregnancy. The study findings constitute the basis for future research into these associations to aid in developing effective policy changes and interventions to minimize the odds of experiencing an unintended pregnancy and its associated consequences.


Late toxicity of brachytherapy after female genital tract tumors treated during childhood: Prospective evaluation with a long-term follow-up.
To prospectively assess the long-term toxicities of brachytherapy in female survivors with localized genital tract tumors. The data concerning 42 patients treated at Gustave Roussy between 1971 and 2004, were both retrospectively and prospectively analyzed. Strictly confidential constructed surveys based on the LENT SOMA/SF-36v2 questionnaires were mailed and 51% were completed. Complications were recorded throughout the follow-up period and graded according to CTCAE, version 4.0. The median age at diagnosis was 1.7 years (range, 0.6-16.6) and most patients (69%) had rhabdomyosarcomas. Treatments included brachytherapy delivered in all patients, chemotherapy (88%), surgery (31%), and external beam radiotherapy (5%). At a median follow-up of 15.5 years, 41/42 patients were alive. A total of 160 late effects were identified in 32/42 (76%) patients: 72% G1-2, and 28% G3-4 (the mean number of all grade late effects per patient: 4 [median: 2.5; range, 0-16] and the mean number of G3-4 late effects per patient: 1[median: 0; range, 0-8]). The most common all grade late toxicities were gynecological (75/160; 47%) and G3-4 were urinary (24/45; 53%). Sixteen patients (38%) required surgical treatment of late complications. The 15-year actuarial incidence rate of G3-4 late effects was 51%. The total number of all grade and G3-4 late effects was significantly increased in patients treated before 1990 (p=0.005 and p=0.008), when the cumulative dose was higher (p=0.03 and p=0.02), when the maximal dose was delivered to the ovaries (p=0.002 and p=0.04), and when the brachytherapy volume was larger (p=0.03 and p=0.02). Quality of life was good or very good in 91% of patients who completed the surveys. Long-term effects decreased with advances in treatment. Stringently controlled brachytherapy parameters should allow us to pursue improvements in order to prevent or minimize long-term sequelae.


Imbalance between the expression dosages of X-chromosome and autosomal genes in mammalian oocytes.
Oocytes have unique characteristics compared with other cell types. In mouse and human oocytes, two X chromosomes are maintained in the active state. Previous microarray studies have shown that the balance of the expression state is maintained in haploid oocytes. Here, we investigated transcripts using RNA-sequence technology in mouse and human oocytes. The median expression ratio between X chromosome and autosomal genes (X:A) in immature mouse oocytes increased as the gene expression levels increased, reaching a value of 1. However, the ratio in mature oocytes was under 1 for all expression categories. Moreover, we observed a markedly low ratio resulting from the bimodal expression patterns of X-linked genes. The low X:A expression ratio in mature oocyte was independent of DNA methylation. While mature human oocytes exhibited a slightly low X:A expression ratio, this was the result of the skewed high frequency of lowly expressed X-linked genes rather than the bimodal state. We propose that this imbalance between the expression dosages of X-chromosome and autosomal genes is a feature of transcripts in mammalian oocytes lacking X-chromosome inactivation.


Limitations of postmortem assessment of human coronary artery size and luminal narrowing: differential effects of tissue fixation and processing on vessels with different degrees of atherosclerosis.
Numerous studies have utilized histologic sections of coronary arteries as the standard for testing the validity of the angiographic determination of coronary artery dimensions. However, little attention has been given to artifactual dimensional changes that occur during fixation and histologic processing of tissues (dehydration, clearing, embedding, sectioning and staining). Using planimetric techniques, the dimensional changes that occurred with fixation and processing were quantitated in 61 coronary artery segments with minimal or moderate to severe atherosclerosis obtained from 12 patients studied at autopsy. In vessels with minimal atherosclerotic narrowing, fixation and processing resulted in a decrease in total vessel cross-sectional area and luminal cross-sectional area (p less than or equal to 0.05), whereas absolute wall area (total vessel cross-sectional area minus luminal cross-sectional area) did not change (p = NS). These disproportionate changes resulted in an alteration in the relation between lumen and wall areas so that luminal cross-sectional area decreased from 47.6 +/- 8.5% of the total vessel cross-sectional area observed before fixation to 36.2 +/- 7% after processing (p less than or equal to 0.05). In vessels with moderate to severe atherosclerosis, both the total cross-sectional area and wall area decreased after fixation and processing (p less than or equal to 0.05), but luminal area did not change (p = NS). As a result, the percent luminal cross-sectional area in these vessels increased from 21.1 +/- 10.1% before fixation to 28.7 +/- 9.7% after processing (p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)


Lipid accumulation and mitochondrial abnormalities are associated with fiber atrophy in the skeletal muscle of rats with collagen-induced arthritis.
Rheumatoid arthritis (RA) has a negative impact on muscle mass, and reduces patient's mobility and autonomy. Furthermore, RA is associated with metabolic comorbidities, notably in lipid homeostasis by unknown mechanisms. To understand the links between the loss in muscle mass and the metabolic abnormalities, arthritis was induced in male Sprague Dawley rats (n = 11) using the collagen-induced arthritis model. Rats immunized with bovine type II collagen were compared to a control group of animals (n = 11) injected with acetic acid and complete Freund's adjuvant. The clinical severity of the ensuing arthritis was evaluated weekly by a semi-quantitative score. Skeletal muscles from the hind limb were used for the histological analysis and exploration of mitochondrial activity, lipid accumulation, metabolism and regenerative capacities. A significant atrophy in tibialis anterior muscle fibers was observed in the arthritic rats despite a non-significant decrease in the weight of the muscles. Despite moderate inflammation, accumulation of triglycerides (P < 0.05), reduced mitochondrial DNA copy number (P < 0.05) and non-significant dysfunction in mitochondrial cytochrome c oxidase activity were found in the gastrocnemius muscle. Concomitantly, our results suggested an activation of the muscle specific E3 ubiquitin ligases MuRF-1 and MAFbx. Finally, the adipose tissue from the arthritic rats exhibited decreased PPARγ mRNA suggesting reduced adipogenic capacities. In conclusion, the reduced adipose tissue adipogenic capacity and skeletal muscle mitochondrial capacity are probably involved in the activation of protein catabolism, inhibition of myogenesis, accumulation of lipids and fiber atrophy in the skeletal muscle during RA.


Multisystem inflammatory syndrome in children and Kawasaki disease: a critical comparison.
Children and adolescents infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are predominantly asymptomatic or have mild symptoms compared with the more severe coronavirus disease 2019 (COVID-19) described in adults. However, SARS-CoV-2 is also associated with a widely reported but poorly understood paediatric systemic vasculitis. This multisystem inflammatory syndrome in children (MIS-C) has features that overlap with myocarditis, toxic-shock syndrome and Kawasaki disease. Current evidence indicates that MIS-C is the result of an exaggerated innate and adaptive immune response, characterized by a cytokine storm, and that it is triggered by prior SARS-CoV-2 exposure. Epidemiological, clinical and immunological differences classify MIS-C as being distinct from Kawasaki disease. Differences include the age range, and the geographical and ethnic distribution of patients. MIS-C is associated with prominent gastrointestinal and cardiovascular system involvement, admission to intensive care unit, neutrophilia, lymphopenia, high levels of IFNγ and low counts of naive CD4+ T cells, with a high proportion of activated memory T cells. Further investigation of MIS-C will continue to enhance our understanding of similar conditions associated with a cytokine storm.


Revision of the genus Homa Distant (Hemiptera: Cicadellidae: Typhlocybinae).
The leafhopper genus Homa Distant is revised. Four new species, H. osificata Xu, Dietrich Qin sp. nov., H. oretinia Xu, Dietrich Qin sp. nov., H. asilata Xu, Dietrich Qin sp. nov., and H. algulata Xu, Dietrich Qin sp. nov., are described from Thailand. H. haematoptilus (Kirkaldy) is redescribed based on specimens from the Oriental Region. All included species are illustrated and a key is provided to separate species for which males are known.


Cannabis use during pregnancy and its effect on the fetus, newborn and later childhood: A systematic review.
Cannabis and its derivatives are becoming increasingly popular in women's preferences during pregnancy in order to relieve nausea. The present study examines cannabis use during pregnancy and its effects on the fetus, newborn and later childhood. All primary studies were searched in the databases: PubMed, Scopus, Medline during the period June 2019 to August 2020. The keywords used were 'pregnancy', 'pregnant women', 'cannabis', 'marijuana', 'fetus', 'newborn', 'childhood', and combined with 'AND' and 'OR' Boolean operators. Inclusion criteria were: pregnant users of cannabis as the study group and pregnant non-users of cannabis as the control group; the articles could be in English or in Greek. The exclusion criteria were: unpublished studies, reviews, presentations at conferences, and animal studies. From the systematic review of the literature, the study included 13 primary research studies in which it was found that the children of mother-user faced: disorders in the sleep cycle, memory problems, hyperactivity, increased chances of low birth weight, prematurity with lower Apgar score in the 1st and 5th minutes and hospitalization in an NICU, DNA methylation at the position CpG.32, and modifications in the brain, especially in the amygdala. In addition, girls had more aggressive behavior at the age of 18 months, shorter breastfeeding period, and neonatal death. The use of cannabis during the gestation period by the mother, aggravates the physical and mental development of the fetus, the newborn and the later childhood.


Diffuse neonatal gastric infarction.
Diffuse neonatal gastric infarction can be a devastating complication of invasion of the gastric wall and vessels by fungi colonizing the gastric mucosa. Even in the presence of extensive transmural necrosis, however, the radiographs do not necessarily show evidence of gastric mucosal abnormality. Instead, plain films and positive contrast studies may erroneously suggest a mechanical gastric outlet obstruction. Ancillary evidence of a devitalized viscus in a baby who appears to have complete gastric outlet obstruction should suggest the diagnosis of gastric infarction.


Biochemical genetics of Chinese hamster cell mutants with deviant purine metabolism: isolation and characterization of a mutant deficient in the activity of phosphoribosylaminoimidazole synthetase.
A new purine-requiring mutant of Chinese hamster ovary cells (CHO-Kl) is described. This mutant, Ade-G, grows on aminoimidazole carboxamide, hypoxanthine, or adenine. It complements all eight of our other previously described Ade- mutants. Biochemical analysis of de novo purine synthesis in whole cells suggests that Ade-G is capable of the first four reactions of de novo purine biosynthesis and that it synthesizes and accumulates phosphoribosylformylglycinamidine (FGAM). Direct enzyme assay in cell-free extracts confirms that Ade-G is defective in phosphoribosylaminoimidazole synthetase activity and does not convert FGAM to phosphoribosylaminoimidazole (AIR), the next intermediate in the de novo biosynthetic pathway.


Competitive inhibition of a tumour cell surface protease. A rapid technique for in vitro testing of selective targeting systems.
The active centre of a protease on the surface of tumour cells can be located by its affinity for an active site-directed inhibitor, 9-amino acridine. Cells which have uninhibited proteases, bind 9-amino acridine and fluoresce in resin sections. The leukaemic rat was used as a model system to provide tumour cells in a well defined location. Drugs when coupled to a ligand (directed to the active centre of the protease) compete for this binding site with 9-amino acridine. Thus, competitive inhibition of the tumour cell surface protease provides a rapid technique for demonstrating the delivery of liganded molecules to the surface of tumour cells in vitro.


Feasibility of stress only rubidium-82 PET myocardial perfusion imaging.
Stress only SPECT myocardial perfusion imaging (MPI) is a validated strategy to streamline cardiac diagnostic imaging. The potential use of Rb82 PET stress only MPI has not been investigated. Stress images from 200 Rb82 PET-MPI were reviewed by two blinded readers and categorized as not requiring additional rest images (normal) or requiring additional images (abnormal or equivocal). No additional images were deemed necessary for 95 (48%) and 99 (50%) by the two blinded readers. The stress only interpretation was compared to the previous read of the complete rest-stress study. The rate of detecting a normal result with stress only reading was 76%-79% with a negative predictive value of 94%-95%. Clinical predictors of a normal stress only PET-MPI included lower age, the absence of CAD, and female gender, but not body mass index. Blinded reads of 50 additional consecutive PET-MPI from patients with selected clinical predictors (age <65 years, no known CAD) were then performed. Of these, 40 (80%) were normal by previous rest-stress reading, and 34 (68%) were categorized as not requiring additional images after stress only reading. PET stress only imaging would have resulted in a mean reduction of radiation exposure of 2.4 mSv per study according to a published radiation estimate. Stress only Rb82 PET-MPI is a feasible strategy to reduce resource utilization and radiation exposure associated with MPI. This strategy would be most applicable to patients with a lower pretest likelihood.


Somatosensory stimulation enhances the effects of training functional hand tasks in patients with chronic stroke.
To test the hypothesis that somatosensory stimulation would enhance the effects of training functional hand tasks immediately after practice and 1 day later in chronic subcortical stroke patients. Single-blinded and randomized, crossover study. Human research laboratory. Nine chronic subcortical stroke patients. Three separate sessions of motor training preceded by (1) synchronous peripheral nerve stimulation (PNS), (2) no stimulation, or (3) asynchronous PNS. Time to complete the Jebsen-Taylor Hand Function Test (JTHFT time) and corticomotor excitability tested with transcranial magnetic stimulation. After familiarization practice, during which all patients reached a performance plateau, training under the effects of PNS reduced JTHFT time by 10% beyond the post-familiarization plateau. This behavioral gain was accompanied by a specific reduction in GABAergically mediated intracortical inhibition in the motor cortex. These findings were not observed after similar practice under the influence of no stimulation or asynchronous PNS sessions. Somatosensory stimulation may enhance the training of functional hand tasks in patients with chronic stroke, possibly through modulation of intracortical GABAergic pathways.