Fibronectin concentrations in lung lavage fluid after inhalation exposure to low levels of metals.
Groups of rabbits were exposed by inhalation to chlorides of cobalt, nickel, and manganese as well as to tri- and hexavalent chromium at metal concentrations ranging from 0.4 to 3.9 mg/m3 for 1-4 months (5 days/week, 6 hr/day). Fibronectin content and lysozyme (muramidase) activity in lavage fluid were measured after all treatments and in alveolar macrophages after treatment with nickel chloride. In the lavage fluid no marked changes were seen in fibronectin content and lysozyme activity after exposure to tri- or hexavalent chromium or manganese. Nickel exposure significantly decreased the lysozyme activity in the lavage fluid and in the macrophages whereas the fibronectin content was unchanged in the lavage fluid and significantly increased in the macrophages. Both fibronectin content and lysozyme activity were increased markedly in the lavage fluid after cobalt exposure.


Parents' Translations of Child Gesture Facilitate Word Learning in Children with Autism, Down Syndrome and Typical Development.
Typically-developing (TD) children frequently refer to objects uniquely in gesture. Parents translate these gestures into words, facilitating children's acquisition of these words (Goldin-Meadow et al. in Dev Sci 10(6):778-785, 2007). We ask whether this pattern holds for children with autism (AU) and with Down syndrome (DS) who show delayed vocabulary development. We observed 23 children with AU, 23 with DS, and 23 TD children with their parents over a year. Children used gestures to indicate objects before labeling them and parents translated their gestures into words. Importantly, children benefited from this input, acquiring more words for the translated gestures than the not translated ones. Results highlight the role contingent parental input to child gesture plays in language development of children with developmental disorders.


Lentzea chajnantorensis sp. nov., an actinobacterium from a very high altitude Cerro Chajnantor gravel soil in northern Chile.
The taxonomic position of a filamentous actinobacterial strain, isolate H45T, recovered from a high altitude Atacama Desert gravel soil, was established using a polyphasic approach. The strain, which is known to produce novel dienes, has chemotaxonomic and morphological properties typical of the genus Lentzea and formed a distinct branch in the Lentzea 16S rRNA gene tree that is closely related to the type strain of Lentzea kentuckyensis. The two strains were distinguished using a combination of phenotypic properties and by a DNA:DNA relatedness value of 37.6 ± 4.0%. On the basis of these genotypic and phenotypic data it is proposed that isolate H45T (=NCIMB 4966T = NRRL B-65282T) be classified in the genus Lentzea as Lentzea chajnantorensis sp. nov.


Acute Severe Mitral Stenosis Immediately After Transcatheter Aortic Valve Implantation.
An 86-year-old female patient was referred for treatment of symptomatic severe aortic stenosis. The heart team decided to perform transfemoral transcatheter aortic valve implantation. A 25 mm transcatheter aortic valve was implanted, but the valve migrated low into the left ventricular outflow tract. The subsequent removal and replacement procedures are described.


Effects of Melatonin on the Body Composition, Physical Performance, and Blood Erythrocyte Indexes of C57Bl/6J Mice Exposed to Continuous Illumination.
Male C57Bl/6J mice were exposed to daily 24-h illumination over 14 days and daily intragastrically received melatonin (1 mg/kg) or water (placebo). Controls were kept under standard day/night (14/10 h) conditions. Melatonin prevented the development of anemia in mice exposed to continuous illumination, which was proven by higher blood hemoglobin levels by the end of the experiment in melatonin-treated animals in comparison with the placebo group. Studies by the low-field NMR spectrometry detected lower lean body mass, total body water, and especially, fat content (by ~13%) in animals receiving placebo. Melatonin treatment led to an increase in the lean body mass and total body water on day 7 (in comparison with the placebo group) without affecting fat mass. On day 14 of continuous illumination, lean body mass increased in comparison with the corresponding parameter in the control and placebo groups. Melatonin had no effect on the physical endurance of mice exposed to continuous illumination (assessed by the grid hanging test).


The development and validation of the Healthy Computing Questionnaire for Children (HCQC).
School children may be at risk of physical health problems associated with desktop, laptop and tablet computer use. There are some interventions designed to educate children about ergonomic practices when using computers. A common limitation of past intervention studies has been the lack of a valid and reliable questionnaire to determine effectiveness of the intervention. The aim of this study was to develop a valid and reliable self-report measure to assess primary school children's knowledge, attitudes and behaviours related to healthy computer use. A mixed methods approach was used to develop the questionnaire and test its psychometric properties. A convenience sample of 440 primary school children in Year 5 (aged 9-11 years) was used in the development and validation of the questionnaire. The final questionnaire comprised 56 items across the three subscales of knowledge, attitudes and behaviour. The questionnaire was shown to have good content validity and adequate test-retest reliability. Internal consistency was adequate for the attitude items, but low for the knowledge items. This study produced a valid and reliable tool, using a health promotion framework, for measuring primary school children's knowledge, attitudes and behaviours related to healthy computing.


Years lived with disability of cancer in China: findings from disability weights measurement with a focus on the effect of disease burden.
Disability weights are crucial for quantifying health loss associated with non-fatal outcomes and were not well assessed in different countries, especially for specific cancer. Therefore, this study aimed to identify disability weights with a focus on specific cancer in a large Chinese population. Two types of web surveys were conducted, and 254 health states, including 30 new states for specific cancer, were investigated using paired comparison methods. The years lived with disability (YLDs) of cancer were calculated as the sum of the prevalence of each sequela of cancer multiplied by its relative disability weight. In total, 44,069 participants were eligible for the disability weights study. The disability weights of 254 health states were estimated. Among those, the disability weights of 18 specific cancer types varied greatly at diagnosis and primary treatment stage, with the value ranging from 0.619 (95% uncertainty interval (UI) 0.606-0.632) for brain cancer to 0.167 (95% UI 0.158-0.176) for oropharyngeal cancer. The discrepancy in YLDs calculated by different disability weights was high, and the largest gap for all cancer combined was approximately 30.14%. When calculated using the cancer-specific disability weights, a total of 1,967,830 (95% UI 1,928,880-2,008,060) YLDs of cancer were recorded in China. The disability weights of cancer varied greatly among cancer types and populations, which had considerable influence on the estimation of the disease burden. Cancer-specific disability weights could provide a more accurate evaluation of the cancer burden.


Hemoglobin guided nanocarrier for specific delivery of amphotericin B to Leishmania infected macrophage.
Leishmania donovani being an intracellular parasite poses many challenges against the attempted chemotherapy. After the resistance towards the first line of antileishmanial drug, Amphotericin B has been the treatment of choice against visceral leishmaniasis, a fatal tropical disease. However, unfavorable toxicity profile, severe side effects, prolonged parenteral administration procedure limits the use of Amphotericin B. Lack of available specific delivery system also makes this drug unsafe for the prolonged use. In this current study, a chitosan-chondroitin sulfate based nanodelivery vehicle has been introduced. Hemoglobin has been attached on the surface of the delivery system for specifically targeting the leishmania infected macrophage taking the advantage of Leishmania being highly auxotrophic for heme. This cheap and biodegradable delivery vehicle has improved the toxicity profile and lowered LD50 value of the drug significantly compared to traditional way of its direct administration.


Correlation among foetal number, corpora lutea and plasma progesterone in Rockland-Swiss mice.
The relationship among plasma progesterone, number of corpora lutea, and foetal number was assessed in Rockland-Swiss albino mice. While number of corpora lutea and foetal number were significantly correlated, neither was related to plasma progesterone level. This finding in the mouse is similar to results reported in the rabbit.


Predominant role of T cell receptor (TCR)-alpha chain in forming preimmune TCR repertoire revealed by clonal TCR reconstitution system.
The CDR3 regions of T cell receptor (TCR)-alpha and -beta chains play central roles in the recognition of antigen (Ag)-MHC complex. TCR repertoire is created on the basis of Ag recognition specificity by CDR3s. To analyze the potential spectrum of TCR-alpha and -beta to exhibit Ag specificity and generate TCR repertoire, we established hundreds of TCR transfectants bearing a single TCR-alpha or -beta chain derived from a cytotoxic T cell (CTL) clone, RT-1, specific for HIVgp160 peptide, and randomly picked up TCR-beta or -alpha chains. Surprisingly, one-third of such TCR-beta containing random CDR3 beta from naive T cells of normal mice could reconstitute the antigen-reactive TCR coupling with RT-1 TCR-alpha. A similar dominant function of TCR-alpha in forming Ag-specific TCR, though low-frequency, was obtained for lymphocytic choriomeningitis virus-specific TCR. Subsequently, we generated TCR-alpha and/or -beta transgenic (Tg) mice specific for HIVgp160 peptide, and analyzed the TCR repertoire of Ag-specific CTLs. Similar to the results from TCR reconstitution, TCR-alpha Tg generated CTLs with heterogeneous TCR-beta, whereas TCR-beta Tg-induced CTLs bearing a single TCR-alpha. These findings of Ag recognition with minimum involvement of CDR3 beta expand our understanding regarding the flexibility of the spectrum of TCR and suggest a predominant role of TCR-alpha chain in determining the preimmune repertoire of Ag-specific TCR.


Selenium and vitamin E in cord blood from preterm and full term infants.
Selenium was determined in erythrocytes and serum, and vitamin E and beta-lipoprotein in serum from cord blood samples of 31 full term and 20 preterm infants. Venous samples from 21 mothers at birth and 15 normal adult women were also analyzed. No difference for either selenium or vitamin E was found between the preterm and full term infants. The selenium concentration in red blood cells was the same for newborn, mothers at birth, and normal adult women. The serum concentration of selenium was, however, significantly lower in the newborn, the mean level in the children being 64% of that in the mothers. The level in the mothers did not differ from that in non-pregnant women. The vitamin E concentration was found to correlate very well with the beta-lipoprotein concentration. This indicates that differences in the transport capacity account for the large difference in the serum tocopherol levels of mothers at birth and newborn.


Chronic anterior tibial compartment syndrome. A light-microscopic, histochemical and electronmicroscopic analysis.
A case of chronic anterior tibial compartment syndrome is reported where the entity was accompanied with a primary neurogenic type of muscle atrophy. Histology, histochemistry and electronmicroscopy indicated the diagnosis. The authors concluded that in a moderate case of leg trauma with peroneal nerve involvement, when it is complicated by intermittent arterial spasm, the anterior tibial compartment syndrome may develop chronically.


Coreactivation of four inactive X genes in a hamster x human hybrid and persistence of late replication of reactivated X chromosome.
Hamster-human hybrids which contained an inactive human X chromosome were treated by 5-azacytidine. Hypoxanthine guanine phosphoribosyltransferase derepressed hybrids were selected and derepression of three other loci, phosphoglycerate kinase, alpha-galactosidase, and glucose-6-phosphate dehydrogenase were studied. Among 32 hybrids selected for hypoxanthine guanine phosphoribosyltransferase, two were found to be reactivated at four X loci. The independence or nonindependence of the reactivation events will be discussed. No correlation was found between the time of replication and the expression or nonexpression of the X chromosome genes: X chromosomes reactivated at four loci remained late replicating; conversely early replication can exist without the expression of some X genes.


Use of Cre/loxP recombination to swap cell binding motifs on the adenoviral capsid protein IX.
We used Cre/loxP recombination to swap targeting ligands present on the adenoviral capsid protein IX (pIX). A loxP-flanked sequence encoding poly-lysine (pK-binds heparan sulfate proteoglycans) was engineered onto the 3'-terminus of pIX, and the resulting fusion protein allowed for routine virus propagation. Growth of this virus on Cre-expressing cells removed the pK coding sequence, generating virus that could only infect through alternative ligands, such as a tyrosine kinase receptor A (TrkA)-binding motif engineered into the capsid fibre protein for enhanced infection of neuronal cells. We used a similar approach to swap the pK motif on pIX for a sequence encoding a single-domain antibody directed towards CD66c for targeted infection of cancer cells; Cre-mediated removal of the pK-coding sequence simultaneously placed the single-domain antibody coding sequence in frame with pIX. Thus, we have developed a simple method to propagate virus lacking native viral tropism but containing cell-specific binding ligands.


[Disseminated cutaneous leishmaniasis in a case of an immunodepressed woman].
The authors report a case of Leishmania major leishmaniasis which occurred in a female kidney transplant recipient. In contrast with visceral leishmaniasis, disseminated cutaneous leishmaniasis seems to be exceptional in immunodepressed patients.


A Book Review of 'Basics of Child Neuropsychology: A Primer for Educators and Clinicians' by Stephen R Hooper.
A Book Review of 'Basics of Child Neuropsychology: A Primer for Educators and Clinicians' by Stephen R. Hooper.


Cytochromes and oxygen radicals as putative members of the oxygen sensing pathway.
This study applies biophysical methods like light absorption spectrophotometry of cytochromes, determination of NAD(P)H-dependent superoxide anion (O2-) formation and localisation of hydroxyl radicals (*OH) by 3-dimensional (3D) confocal laser scanning microscopy to reveal in human cells putative members of the oxygen sensing signal pathway leading to enhanced gene expression under hypoxia. A cell membrane localised non-mitochondrial cytochrome b558 seems to be involved as an oxygen sensor in the hepatoma cell line HepG2 in cooperation with the mitochondrial cytochrome b563 probably probing additionally metabolic changes. *OH the putative second messenger of the oxygen sensing pathway generated by a Fenton reaction could be visualized in the perinuclear space of the three human cell lines used. Substances like cobalt or the iron chelator desferrioxamine, which have been applied in HepG2 cells to mimic hypoxia induced gene expression, interact on various sides of the oxygen sensing pathway confirming the importance of b-type cytochromes and the Fenton reaction.


Lipoprotein lipase of ovarian follicles in the domestic chicken (Gallus domesticus) (38537).
A lipase, bearing the characteristics of adipose tissue lipoprotein lipase (LPL) has been characterized in avian ovarian granulosa cells. The activity is low in cells from follicles weighing less than 0.5 g; in heavier follicles which have entered the rapid growth phase, significant activity (1 mumole fatty acid/mg protein/hr) could be identified. Granulosa LPL provides follicular tissues with the requisite enzyme system to hydrolyze very low density lipoprotein triglyceride en route to the oocyte.


Somatic growth, aging, and longevity.
Although larger species of animals typically live longer than smaller species, the relationship of body size to longevity within a species is generally opposite. The longevity advantage of smaller individuals can be considerable and is best documented in laboratory mice and in domestic dogs. Importantly, it appears to apply broadly, including humans. It is not known whether theses associations represent causal links between various developmental and physiological mechanisms affecting growth and/or aging. However, variations in growth hormone (GH) signaling are likely involved because GH is a key stimulator of somatic growth, and apparently also exerts various "pro-aging" effects. Mechanisms linking GH, somatic growth, adult body size, aging, and lifespan likely involve target of rapamycin (TOR), particularly one of its signaling complexes, mTORC1, as well as various adjustments in mitochondrial function, energy metabolism, thermogenesis, inflammation, and insulin signaling. Somatic growth, aging, and longevity are also influenced by a variety of hormonal and nutritional signals, and much work will be needed to answer the question of why smaller individuals may be likely to live longer.


The effect of cancer on sperm DNA fragmentation as measured by the sperm chromatin dispersion test.
The percentage of spermatozoa with fragmented DNA from cancer patients before surgery, chemotherapy, or radiotherapy treatments was compared with infertile male patients in an assisted reproduction program and with sperm donors of proven fertility. The percentages of DNA fragmentation were 34.3% in cancer patients, 30.9% in infertile men whose partners did not become pregnant, 28.8% in men who partners became pregnant, and 10.8% in fertile sperm donors. The DNA fragmentation of sperm donors was statistically significantly lower compared the other groups. No statistically significant differences were found in the levels of DNA fragmentation when comparing cancer types, including those of testicular origin.


Polyene macrolide antibiotics: indirect stimulation of the Na+/H+ exchanger of BALB/c B lymphoid cell line, A20.
The fluorescent pH probe, 2'-7'-bis (carboxyethyl) 5-carboxyfluorescein, was used to follow changes in internal pH (pHi) induced by aromatic polyene antibiotics in the BALB/c lymphoid cell line A20. The antibiotics studied were vacidin, which contains a free carboxylic group in the position C18 of the macrolide ring, and vacidin glycyl methyl ester and perimycin, which are without free carboxylic groups. Although all of them induced transmembrane Na+ and K+ movements, only vacidin had protonophoric activity, as previously demonstrated for red blood cells [Cybulska B et al., Biochem Pharmacol 38: 1755-1762, 1989]. However, with all three antibiotics, pHi changes were observed in A20 cells. It was demonstrated that the transmembrane H+ movements resulted to different degrees, principally in the case of perimycin and vacidin glycyl methyl ester, or partially in the case of vacidin, from the stimulation of the Na+/H+ exchanger by the induced Na+ permeability. The non-aromatic polyene antibiotic amphotericin B had a low ability to increase proton permeability.


Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial.
Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common. To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome. Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years. Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams. Increasing PSA level (ie, biochemical failure) 5 years after treatment. The proportions of men free from biochemical failure at 5 years were 78.8% [corrected] (95% confidence interval, 73.1%-84.6%) [corrected] for conventional-dose and 91.3% [corrected] (95% confidence interval, 87.2%-95.4%) [corrected] for high-dose therapy (P<.001), a 59% [corrected] reduction in the risk of failure. The advantage to high-dose therapy was statistically significant [corrected] in both the low-risk subgroup [corrected] (risk reduction, 84% [P<.001]) [corrected] There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater. Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.


Evaluating hearing performance with cochlear implants within the same patient using daily randomization and imaging-based fitting - The ELEPHANT study.
Prospective research in the field of cochlear implants is hampered by methodological issues and small sample sizes. The ELEPHANT study presents an alternative clinical trial design with a daily randomized approach evaluating individualized tonotopical fitting of a cochlear implant (CI). A single-blinded, daily-randomized clinical trial will be implemented to evaluate a new imaging-based CI mapping strategy. A minimum of 20 participants will be included from the start of the rehabilitation process with a 1-year follow-up period. Based on a post-operative cone beam CT scan (CBCT), mapping of electrical input will be aligned to natural place-pitch arrangement in the individual cochlea. The CI's frequency allocation table will be adjusted to match the electrical stimulation of frequencies as closely as possible to corresponding acoustic locations in the cochlea. A randomization scheme will be implemented whereby the participant, blinded to the intervention allocation, crosses over between the experimental and standard fitting program on a daily basis, and thus effectively acts as his own control, followed by a period of free choice between both maps to incorporate patient preference. With this new approach the occurrence of a first-order carryover effect and a limited sample size is addressed. The experimental fitting strategy is thought to give rise to a steeper learning curve, result in better performance in challenging listening situations, improve sound quality, better complement residual acoustic hearing in the contralateral ear and be preferred by recipients of a CI. Concurrently, the suitability of the novel trial design will be considered in investigating these hypotheses. ClinicalTrials.gov: NCT03892941. Registered 27 March 2019.


Organically modified clay supported chitosan/hydroxyapatite-zinc oxide nanocomposites with enhanced mechanical and biological properties for the application in bone tissue engineering.
The objective of this study is to design biomimetic organically modified montmorillonite clay (OMMT) supported chitosan/hydroxyapatite-zinc oxide (CTS/HAP-ZnO) nanocomposites (ZnCMH I-III) with improved mechanical and biological properties compared to previously reported CTS/OMMT/HAP composite. Fourier transform infrared spectroscopy, powder X-ray diffraction, scanning electron microscopy and transmission electron microscopy were used to analyze the composition and surface morphology of the prepared nanocomposites. Strong antibacterial properties against both Gram-positive and Gram-negative bacterial strains were established for ZnCMH I-III. pH and blood compatibility study revealed that ZnCMH I-III should be nontoxic to the human body. Cytocompatibility of these nanocomposites with human osteoblastic MG-63 cells was also established. Experimental findings suggest that addition of 5wt% of OMMT into CTS/HAP-ZnO (ZnCMH I) gives the best mechanical strength and water absorption capacity. Addition of 0.1wt% of ZnO nanoparticles into CTS-OMMT-HAP significantly enhanced the tensile strengths of ZnCMH I-III compared to previously reported CTS-OMMT-HAP composite. In absence of OMMT, control sample (ZnCH) also showed reduced tensile strength, antibacterial effect and cytocompatibility with osteoblastic cell compared to ZnCMH I. Considering all of the above-mentioned studies, it can be proposed that ZnCMH I nanocomposite has a great potential to be applied in bone tissue engineering.


Occupational disparities in survival in Korean women with cancer: a nationwide registry linkage study.
We sought to examine occupational disparities in survival among Korean women diagnosed with cancer. Population-based, registry-linkage study. South Korea. Our study population comprised female workers registered in the Korean national employment insurance programme during 1995-2000 and diagnosed with cancer between 1995 and 2008. A total of 61 110 women with cancer diagnoses was included in analysis. The occupation was categorised into four groups: (1) managers, professionals and technical workers, (2) clerks, (3) service/sales workers and (4) blue-collar workers. Study population were linked to the national death registry until 2009. HRs for mortality adjusting for age and year of diagnosis were calculated in the study sample and subgroups with 10 specific cancer sites including thyroid, breast, stomach, cervix, colon or lung cancer using managers, professionals and technical workers as the reference. Women in service/sales (HR 1.25, 95% CI 1.15 to 1.35) and blue-collar occupations (HR 1.34, 95% CI 1.25 to 1.44) had poorer survival for all cancer sites combined, while blue-collar workers showed poorer survival for lung (HR 1.41, 95% CI 1.14 to 1.77), breast (HR 1.28, 95% CI 1.06 to 1.54), cervical cancer (HR 1.42, 95% CI 1.02 to 2.06) and non-Hodgkin's lymphoma (HR 1.69, 95% CI 1.09 to 2.77) compared with women in professional and managerial positions. We found substantial and significant inequalities in overall survival by the occupational group among Korean women with cancer, even in the context of universal access to cancer screening and treatment.


Active ribosomal cistrons and their primary transcripts located in the nucleolus.
We have located the active ribosomal cistrons together with their primary transcripts and the associated proteins and enzymes forming the typical 'christmas tree' configuration in the dense nucleolar components. Our results can thus correlate the structural and functional organization of the nucleolus.


Haplotype diversity: the link between statistical and biological association.
In the rapidly growing field of association mapping in plants, the use of (marker) haplotypes rather than single markers can be an effective way of improving detection power. Here, we highlight the information that can be obtained from deducing the historical relationships between haplotypes. The ordering of haplotype classes according to deduced historical relationships should further enhance association detection power, but can also be used to predict the genotypic and phenotypic values of unobserved germplasm.


Isolation, long-term culture, and ultrastructural characterization of adult cardiomyopathic cardiac muscle cells.
A long-term cell culture system for adult cardiomyopathic hamster cardiac muscle cells has been established. The diseased and control hearts were dissociated into single cell suspension with the modifications of our previous technique using collagenase and hyaluronidase as applied to the dissociation of the adult rat heart. The postperfusion of the diseased heart with Krebs-Ringer phosphate buffer and bovine serum albumin was very helpful in obtaining greater yield of viable diseased muscle cells; the cells were cultured for 4 wk. Approximately 60% of the myocytes from the diseased heart and 85% of the myocytes from the normal heart attached to the substrates and survived throughout the culture period. Approximately 60 to 70% of the cardiac myocytes from the diseased and control hearts were bi- or multinucleated; 30% of the diseased and 80% of the normal myocytes showed rhythmic contractility. Electron microscopy revealed the presence of two kinds of cardiac muscle cells in the diseased cell culture on the basis of their myofibril content: one with scanty myofibrils and another with abundant myofibrils. Myocytes with sparse myofibrils showed certain characteristic features that included autophagic vacuoles, amorphous matrix of fine filamentous texture, scattered strips of myofibrils, and abnormal organization of the Z-line. Cardiac muscle cells with abundant myofibrillar content contained unorganized myofibrils in certain sarcomeres. These studies demonstrate the feasibility of maintaining diseased cardiac muscle cells from adult cardiomyopathic hamsters for at least 4 wk in monolayer culture.


Endoplasmic reticulum stress contributes to autophagy and apoptosis in cantharidin-induced nephrotoxicity.
Mylabris, as a natural product of traditional Chinese medicine (TCM), exhibiting typical antitumor activity, and cantharidin (CTD) is the major bioactive component. However, drug-induced nephrotoxicity (DIN) extremely limited its clinical application. In this study, we proved that activation of the endoplasmic reticulum (ER) stress-dependent PERK/CHOP pathway exerts a toxic role in rats and HK-2 cells through inducing autophagy and apoptosis. Results showed that CTD could cause renal function damage, cytotoxicity, and apoptosis. The ER dilatation and autolysosomes were observed after CTD treatment. Furthermore, the distribution of LC3, ATF4, and CHOP proteins was observed in the nucleus and cytoplasm. In addition, the mRNA levels of ER stress-regulated genes (PERK, eIF2α, CHOP, and ATF4) were increased, and the expression levels of GRP78, ATF4, CHOP, LC3, Beclin-1, Atg3, Atg7, Caspase 3, and Bax/Bcl-2 proteins were increased both in vitro and in vivo. Consistently, this upregulation could be inhibited by an ER stress inhibitor 4-Phenylbutyric acid (4-PBA), indicating that ER stress is partly responsible for activation of autophagy and apoptosis in CTD-induced DIN. In conclusion, CTD could induce DIN by triggering ER stress, further activating autophagy and apoptosis both in vivo and in vitro.


An old confusion: Entomophthoromycosis versus mucormycosis and their main differences.
Fungal diseases were underestimated for many years. And the global burden of fungal infections is substantial and has increased in recent years. Invasive fungal infections have been linked to several risk factors in humans which basically depend on the individual homeostasis of the patients. However, many fungi can infect even apparently healthy people. Knowledge of these pathogens is critical in reducing or stopping morbidity and/or mortality statistics due to fungal pathogens. Successful therapeutic strategies rely on rapid diagnosis of the causative fungal agent and the underlying disease. However, the terminology of the diseases was updated to existing phylogenetic classifications and led to confusion in the definition of mucormycosis, conidiobolomycosis, and basidiobolomycosis, which were previously grouped under the now-uncommon term zygomycosis. Therefore, the ecological, taxonomic, clinical, and diagnostic differences are addressed to optimize the understanding and definition of these diseases. The term "coenocytic hyphomycosis" is proposed to summarize all fungal infections caused by Mucorales and species of Basidiobolus and Conidiobolus.


The demonstration of very low density lipoprotein in the basal lamina of the granulosa layer in the hen's ovarian follicle.
The isolated basal lamina from the granulosa layer in ovarian follicles of the domestic fowl contains an abundance of spherical particles with a modal cross-sectional diameter of 25-30 nm. The lipid in this basal lamina is predominantly triacylglycerol and its total fatty acid composition resembles that of plasma very low density lipoprotein (VLDL). Immunodiffusion studies and immunoelectrophoresis indicated that this basal lamina contains diffusible antigen identifiable with plasma VLDL. Perfusion with an alkaline buffer displaced the particles from the basal lamina and subsequent perfusion with plasma VLDL in an acidic buffer resulted in the reappearance of particles of similar size and form. Alternatively, when the perfused basal lamina was subsequently perfused with VLDL-free serum, few particulate structures were observed. Measurements of total and VLDL triacylglycerol together with electron microscope studies of the untreated and of the perfused basal lamina provided further evidence for the identification of the majority of particles with plasma VLDL. Other particulate lipoprotein is most probably plasma low density lipoprotein (LDL). These studies demonstrated that this basal lamina is permeable to the circulating VLDL of the laying fowl.


Orbital computed tomography. Does it help in diagnosing the infiltration of choroid, sclera and/or optic nerve in retinoblastoma?
High-resolution computerized tomography of the orbit was performed in patients with histologically proven retinoblastoma to assess the efficacy of CT in delineating the retro-orbital extent of the tumor and determining if the optical nerve was involved. High-resolution CT proved able to accurately delineate tumor size, tumor localization, tumor calcification, retro-orbital and intracranial tumor growth. Microscopical tumor spread past the lamina cribrosa of the optic nerve, however, could not be detected by CT.


Intrinsic motoneuron excitability is reduced in soleus and tibialis anterior of older adults.
Age-related deterioration within both motoneuron and monoaminergic systems should theoretically reduce neuromodulation by weakening motoneuronal persistent inward current (PIC) amplitude. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70 ± 4 years) and 17 young adults (29 ± 5 years) to investigate motor unit discharge behaviors. Participants performed triangular-shaped plantar and dorsiflexion contractions to 20% of maximum torque at a rise-decline rate of 2%/s of each participant's maximal torque. Pairwise and composite paired-motor unit analyses were adopted to calculate delta frequency (ΔF), which has been used to differentiate between the effects of synaptic excitation and intrinsic motoneuronal properties and is assumed to be proportional to PIC amplitude. Soleus and tibialis anterior motor units in older adults had lower ΔFs calculated with either the pairwise [-0.99 and -1.46 pps; -35.4 and -33.5%, respectively] or composite (-1.18 and -2.28 pps; -32.1 and -45.2%, respectively) methods. Their motor units also had lower peak discharge rates (-2.14 and -2.03 pps; -19.7 and -13.9%, respectively) and recruitment thresholds (-1.50 and -2.06% of maximum, respectively) than young adults. These results demonstrate reduced intrinsic motoneuron excitability during low-force contractions in older adults, likely mediated by decreases in the amplitude of persistent inward currents. Our findings might be explained by deterioration in the motoneuron or monoaminergic systems and could contribute to the decline in motor function during aging; these assumptions should be explicitly tested in future investigations.


Correlation between cyclophosphamide-induced viral susceptibility and depletion of Junin virus-induced suppressor populations.
In contrast to lymphocytic choriomeningitis virus, another arenavirus, Junin virus (JV), the etiologic agent of Argentine hemorrhagic fever, when inoculated into suckling mice, induces lethal meningoencephalitis characterized by a delayed-type hypersensitivity (DTH)-like immune response. However, the adult BALB/c mouse is resistant to infection and no DTH reaction can be seen. This different viral sensitivity may be related to the development of an antigen non-specific DTH-suppressor cell pathway at work in the adult mouse. When the resistant mice are treated with cyclophosphamide (Cy) (50 mg/kg each dose) given at days -1,+1,+4 (zero: infection day), animals become susceptible and develop DTH reaction in brain that leads to death. We analyze the influence of the timing of Cy administration on the suppressor system developing after infection. It was found that Cy depletes the previously described JV-induced suppressor populations (Tsv) but a new suppressor cell (Tsv*) is disclosed bearing the Thy 1+ Ly1+2- phenotype which is unable to depress DTH in Cy-treated animals. With only two doses of Cy corresponding to days -1 and +1, the target of Tsv* cells is depleted but the third dose is still required to achieve full depletion of Tsv cells which are able to employ the Cy-resistant antigen-specific suppressor cells as targets. Since the Cy treatment is able to deplete the Tsv population together with the target of Tsv* cells, animals became unable to regulate lethal DTH reaction. Thus, a cellular explanation for an empirically established Cy schedule able to abrogate the adult mouse resistance to JV is proposed.


Exposure assessment of a cyclist to particles and chemical elements.
Cycle paths can be used as a route for active transportation or simply to cycle for physical activity and leisure. However, exposure to air pollutants can be boosted while cycling, in urban environments, due to the proximity to vehicular emissions and elevated breathing rates. The objective of this work was to assess the exposure of a cyclist to particles and to chemical elements by combining real-time aerosol mass concentration reading equipment and biomonitoring techniques. PM10 and PM2.5 were measured on three cycle paths located in Lisbon, during weekdays and weekends and during rush hours and off-peak hours resulting in a total of 60 campaigns. Lichens were exposed along cycle paths for 3 months, and their element contents were measured by instrumental neutron activation analysis using the k 0 methodology (k 0-INAA). Using a bicycle commute route of lower traffic intensity and avoiding rush hours or other times with elevated vehicular congestion facilitate a reduction in exposure to pollutants. The implementation of cycle paths in cities is important to stimulate physical activity and active transportation; however, it is essential to consider ambient air and pollutant sources to create safer infrastructures.


Decomposing the gap in intimate partner violence between Scheduled Caste and General category women in India: An analysis of NFHS-5 data.
Scheduled Caste (SC) women, one of India's most oppressed and neglected population groups, are the most vulnerable to intimate partner violence (IPV). IPV, on the other hand, is less common among women in the General category. No study has been conducted to measure the gap in IPV between these two groups. This study is an attempt to fill this gap. This study aims to comprehensively explore the factors that underlie and explain the gap in IPV between SC and General women. Information on 10,168 ever-married SC and 9695 ever-married General women aged 15-49 from the fifth round of the National Family Health Survey was analyzed. The Fairlie decomposition (Blinder-Oaxaca decomposition modified for binary outcomes) was used in this study to explain the gap in ever experience of IPV prevalence between SC and General women. About 37.3% and 24.4% of ever-married SC and General women in India suffered either physical or mental or sexual violence from their husbands. The large part of the gap in IPV between SC and General women was due to differences in husbands' alcohol consumption (26.33% gap), wealth index (24.48% gap), controlling behavior by husband (24%) and parental IPV (15.87% gap). With the introduction of appropriate interventions and programs, these gaps can be reduced. Interventions aimed at reducing alcoholism should be emphasized.


Synaptic connexions between primary afferents and thoracic motoneurones in the frog.
Synaptic actions were evoked in thoracic motoneurones of the isolated frog spinal cord by 6th or 7th dorsal root volleys or impulses in single primary afferents. In a few cases the impaled motoneurones or the whole dorsal root were filled with horseradish peroxidase. Although HRP labelling has revealed that motoneurones have extensive dendritic arborizations extending into the dorsal horn, the zone in which thoracic dorsal root afferents terminate, there is no positive evidence for a direct link between them. Synaptic actions produced in thoracic motoneurones by dorsal root stimulation are mediated via interneurones and do not involve direct sensorimotor synapses. This conclusion is in agreement with results of simultaneous intracellular recording from motoneurones and individual dorsal root fibres afferent to them.


'Great fleas have little fleas': Irish student midwives' views of the hierarchy in midwifery.
Many studies have investigated the world of the student nurse, but there is little work into the lives and experiences of student midwives. Studies of Irish midwives' provision of care have demonstrated that they are not fulfilling their complete role, and research into their education was deemed to be necessary. To explore the opinions, feelings and views of student midwives as they progressed through their 2-year education programme in Ireland. Both quantitative and qualitative methods were used and the qualitative sections of the study were guided by the phenomenological approach. Ethical approval was granted. All students in the first intake of 1995 in all seven midwifery schools in Southern Ireland agreed to take part (n=125). Individual and group interviews, diary-keeping and questionnaires collected data. The findings presented in this paper describe the students' views of the hierarchical structures in midwifery, and the role and behaviours of the 'Matron'. The data describes a subculture of nursing/midwifery subordination. One reason for the hierarchical nature of the midwifery profession may be because it is an almost totally female-dominated profession, with the female hierarchy exercising control over other women within a male-based power structure. Many hospitals preferred to employ their own students as staff, ensuring a continuation of the hierarchical regime. The recurring nature of this problem may be because midwives now fear change more than they desire it. Further research is required to ascertain whether the reason for the strong hierarchy is because of the continuation of midwifery from the male-dominated profession of nursing, to the existence of the industrial/economic model of maternity care or to the impact of the medicalization of childbirth.


Delinquency: the learning disabled students reaction to academic school failure?
Support for the relationship between academic performance and delinquency is offered. Additionally a review is provided describing the learning disabled male adolescent as the target population for experimental research.


Surveillance of women at high risk for hereditary ovarian cancer is inefficient.
To determine the effectiveness of annual gynaecological screening (pelvic examination, transvaginal ultrasound, and CA-125), a prospective cohort study of women at high risk for hereditary ovarian cancer was conducted. Women were offered DNA analysis followed by either annual screening or prophylactic bilateral salpingo-oophorectomy (BSO). Study population consisted of 512 high-risk women (median follow-up 2.07 years, range 0-9.4 years): 265 women (52%) had a BRCA mutation. Persisting abnormalities indicated diagnostic surgery in 24 women resulting in one primary ovarian cancer FIGO stage IIIc was found. The effectiveness of screening was studied by calculating the probability of finding ovarian cancers in the BRCA-1 and BRCA-2 carrier group and comparing this to the identified number of ovarian cancers. The number of ovarian cancer patients found at surveillance was in accordance with the predicted number of ovarian cancers. A total number of 169 women underwent prophylactic BSO: one ovarian cancer stage IIb was found. In conclusion, the surveillance programme for hereditary ovarian cancer does identify patients with ovarian cancer but is very inefficient considering the high number of surveillance visits and the advanced stage of ovarian cancer in the identified patient. For prevention of advanced stage ovarian cancer, prophylactic BSO from age 35-40 years is a more efficient alternative.


Efficacy and safety of a generic rosuvastatin in a real-world setting: prospective, observational clinical study in Lebanese patients.
No published studies have assessed the efficacy and safety of rosuvastatin generics. Primary objective to assess the safety and efficacy of a generic rosuvastatin in reducing plasma low-density-lipoprotein cholesterol (LDL-C) in Lebanese dyslipidemic patients. Changes in high-density lipoprotein cholesterol, triglycerides and adverse effects were secondary objectives. Prospective, observational, non-comparative. Multiple outpatient clinics in Lebanon. Dyslipidemic patients requiring statin therapy were followed for 2 months after prescription of a generic rosuvastatin at the physician's discretion. Efficacy and safety measurements were collected from medical records. Efficacy was assessed based on the evaluation of mean and percent change in LDL-C between baseline and week 8 as well as the proportion of patients reaching target LDL-C levels. Safety was assessed based on the evaluation of the incidence of adverse events (AEs) during the study period. Two months after initiation of generic rosuvastatin, LDL-C levels in the 313 eligible patients who completed the study significantly decreased from 4.3 (0.8) mmol/L (168.2 [31.3] mg/dL) at baseline to 2.7 (0.7) mmol/L (105.9 [25.5] mg/dL) (P < .001). The mean percent change in LDL-C level was highest in subjects receiving generic rosuvastatin at a dose of 40 mg/day (-47.4%), followed by 20 mg/day (-36.8%), and 10 mg/ day (-31.4%); 82.5% of patients reached the target LDL-C level as set by their physician at baseline. Thirteen patients (4%) reported six AEs during treatment: abdominal pain, headache, stomach ache, insomnia, musculoskeletal pain/myalgia and nausea. No clinically significant changes in serum creatinine, serum creatine kinase, or liver function tests were reported. One patient withdrew because of an adverse event. Generic rosuvastatin was efficacious and safe in reducing LDL-C levels and helping the majority of patients achieve LDL-C targets after a short treatment period. The observational nature, and a control group, and the relatively short duration of follow-up limit the generalizability of results. The authors received fees for study activities at patient visits from an independent clinical research organization subcontracted by the sponsor.


Retinal hemorrhages due to intracranial hypertension, is it possible to differentiate them from those associated with abuse?
Retinal hemorrhages (RHs) are suggestive of abusive head trauma (AHT). Even so, controversy persists about other possible causes, a fact that hinders the diagnosis of abuse. To determine the prevalence and patterns of RHs associated with increased intracranial pressure (ICP) in young children. Prospective, single center study of children aged 29 days-3 years undergoing a lumbar puncture with opening pressure (OP) measured during routine clinical care in the emergency department, over a 4-year period. Children with known causes of RHs were excluded. All the children underwent a detailed ophthalmological examination within 72 h of admission. For children with RHs, an in-depth investigation was carried out to rule out AHT. Thirty-four patients were included: 20(58.8 %) were boys, median age 11.7 months (range 1-33 months). Overall, 29(85.3 %) had clinical findings of increased ICP. The duration of symptoms was ≤4 days in all patients except one, in whom it was 1.5 months. The median OP was 27cmH2O (range 20-60cmH2O). One of the children was found to have RHs, with evaluation resulting in a diagnosis of AHT. No RHs were found in any of the others studied. Using the Wilson method, we can be confident to an upper limit of 95 % that the probability of RHs occurring secondary to increased ICP alone is at most 0.1. RHs were not detected in patients with isolated nontraumatic increased ICP, measured via OP and diagnosed in the ED. Therefore, if RHs are detected, investigation into the possibility of AHT is warranted.


Degree and pattern of dual-task interference during walking vary with component tasks in people after stroke: a systematic review.
What are the degree and pattern of dual-task interference during walking in people after stroke? How do these vary with disease chronicity and different component tasks in people after stroke? How does dual-task interference differ between people after stroke and people without stroke? Systematic review with meta-analysis of studies reporting gait-related dual-task interference. People after stroke and people without stroke. Measures of walking and secondary (cognitive or manual) task performance under dual-task conditions relative to those under single-task conditions. Seventy-six studies (2,425 people after stroke and 492 people without stroke) were included. Manual and mental tracking tasks imposed the greatest dual-task interference on gait speed, although there was substantial uncertainty in these estimates. Among mental tracking tasks, the apparently least-complex task (serial 1 subtractions) induced the greatest dual-task interference (-0.17 m/s, 95% CI -0.24 to -0.10) on gait speed, although there was substantial uncertainty in these estimates. Mutual interference (decrement in both walking and secondary component task performances during dual-tasking) was the most common dual-task interference pattern. The results of the sensitivity analyses for studies involving people with chronic stroke were similar to the results of the primary analyses. The amount of dual-task interference from a mental tracking or manual task during walking was similar between people with or without stroke. The degree and pattern of dual-task interference vary with the choice of component tasks. When evaluating limitations to functional mobility during dual-tasking conditions and in planning interventions accordingly, clinicians should select dual-task assessments that correspond to the daily habits and physical demands of people after stroke. CRD42017059004.


Kaufman oculocerebrofacial syndrome: report of two new cases and further delineation.
Two unrelated Mexican girls, aged 14 months and 6 years respectively, with Kaufman oculocerebrofacial syndrome, are reported. Both showed psychomotor retardation, microcephaly, blepharophimosis and delayed growth as the main features; the infant also presented preauricular tags and large clitoris. Comparative analysis with previous cases reveals a heterogeneous syndrome in which the micro-brachycephaly, the mongoloid slanted eyes with different anomalies, the micrognathia and the neonatal respiratory distress are the most typical characteristics of this mental retardation syndrome.


A randomized controlled trial of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone for clomifene-citrate-resistant polycystic ovary syndrome.
To examine the efficacy of clomifene citrate, metformin, and pioglitazone versus letrozole, metformin, and pioglitazone among women with polycystic ovary syndrome (PCOS) resistant to clomifene citrate. A prospective double-blind randomized controlled trial of women younger than 40 years who had primary/secondary infertility associated with PCOS and had not ovulated in response to clomifene citrate regimens previously was conducted at a center in Cairo, Egypt, between August 1, 2013, and December 31, 2014. Computer-generated random number tables and opaque envelopes were used to assign participants to group A or group B. Participants allocated to group A received 100mg clomifene citrate daily for 5 days from the third day of the menstrual cycle, whereas those in group B received 5mg letrozole daily in the same regimen. All patients received 850 mg metformin and 15 mg pioglitazone for 10 days from the first day of the menstrual cycle. The primary outcome was cumulative ovulation rate. Analyses were by intention to treat. Fifty women were assigned to each group. Ovulation occurred in 108 (92.3%) of 117 cycles in group A and 93 (86.9%) of 107 cycles in Group B (P=0.184). Combined treatment with letrozole, metformin, and pioglitazone was efficacious among women with PCOS resistant to clomifene citrate. ClinicalTrials.gov: NCT01909141.


Cardiovascular Risk of Nonsteroidal Anti-inflammatory Drugs and Classical and Selective Cyclooxygenase-2 Inhibitors: A Meta-analysis of Observational Studies.
The purpose of this study was to review the published evidence on the clinical use of nonsteroidal anti-inflammatory drugs (NSAIDs) and to assess the cardiovascular risk (CVR) of cyclooxygenase-2 inhibitors (coxibs), excluding aspirin, by means of a meta-analytic procedure. A search was conducted on MEDLINE and EMBASE databases between October 1999 and June 2018. Cohort and case-control studies showing CVR as relative risk (RR), odds ratio, hazard ratio, or incidence rate ratio associated with NSAIDs versus no treatment were selected. We estimated the pooled RR and the 95% confidence interval (CI) for all NSAIDs as a whole and individually. Eighty-seven studies met the inclusion criteria. Overall, NSAIDs were found to be associated with a statistically significantly increased CVR (RR, 1.24 [95%CI, 1.19-1.28]). The risk was slightly higher for coxibs (RR, 1.22 [95%CI, 1.17-1.28]) as compared with nonselective NSAIDs (RR, 1.18 [95%CI, 1.12-1.24]). Data analysis by drug disclosed that rofecoxib (RR, 1.39 [95%CI, 1.31-1.47]), followed by diclofenac (RR, 1.34 [95%CI, 1.26-1.42]) and etoricoxib (RR, 1.27 [95%CI, 1.12-1.43]) were the NSAIDs associated with the highest CVR. Analysis by type of event showed that the highest risk corresponded to vascular events for both coxibs (RR, 2.18 [95%CI, 1.72-2.78]) and nonselective NSAIDs (RR, 2.46 [95%CI, 2.00-3.02]). The meta-analysis results suggest that the use of the marketed coxibs celecoxib and etoricoxib would be related to a statistically significant CVR increase. Etoricoxib CVR could be higher than that for celecoxib. This increment would be similar to classical NSAID CVR.


Critical chromatography in ternary solvents.
The behaviour of PMMA standards in mixtures composed of two binary critical eluents was investigated. It was found that combinations of two critical eluents do not result in a molar mass independent elution (critical conditions). When mixing two binary critical eluents, elution might occur in SEC, LAC or close to critical conditions in a non-predictable fashion. It can be assumed that the deviation from critical conditions is caused by preferential adsorption of some eluent components to the stationary phase or the polymer. In order to have a fast estimate, in which mode of chromatography elution will occur when mixing two critical eluents, ternary critical conditions were estimated from gradient experiments. A good agreement was observed between the so obtained critical lines and the elution behaviour resulting in mixtures of two critical eluents.


Characterization of presbyequilibrium among institutionalized elderly persons.
The aim was to characterize dizziness, vertigo, poor maintenance of posture, and sudden instabilities (called presbyequilibrium) among institutionalized elderly to model and identify possible treatable causes. A questionnaire based study focusing on symptoms among 72 elderly persons from a single residential facility and followed them for 3 years. Dizziness, vertigo, poor maintenance of posture, and black-outs were reported by 68% of the 72 elderly and make them at risk for falls, and reduced quality of life. The most common complaint was postural instability, with a tendency to fall. "Spinning" vertigo and "floating" sensation had a strong inter-correlation and correlated with habitual falls. The various dizziness symptoms often occurred in combinations. Attacks of self-experienced syncope never occurred alone but always in combination with "spinning vertigo" or "tendency to fall". In factorial analysis, presbyequilibrium could be divided into six categories. Two of these categories correlated with falls. Among elderly, presbyequilibrium is commonly characterized by a combination of phenomena involving perceptual, orientation, postural, and autonomic manifestations. It is often difficult to obtain an accurate history from the elderly and the presence of vestibular symptoms is frequently overlooked. Taking a careful history and utilizing the classification of symptoms that emerged from the factorial analysis may give a deeper understanding of the etiology of presbyequilibrium, thereby facilitating appropriate rehabilitation.


Assessing mitochondria biogenesis.
Mitochondria have their own DNA (mtDNA) and hence biogenesis of mitochondria requires a coordination of nuclear and mtDNA, both of which encode for mitochondria proteins. Our understanding of the molecular control of mitochondria biogenesis has increased in recent years, providing key signatures of the process. To determine whether or not a tissue or an organ of human or animal origin is undergoing mitochondria biogenesis, multiple parameters should be analyzed. First and foremost is visualization and measurement of mitochondria mass/volume in histological sections using fluorescent mitochondria dyes and light microscopy or transmission electron microscopy to yield quantitative results. To confirm or extend these types of analysis, biochemical markers of mitochondria biogenesis should also be included, including assessment of mtDNA copy number, steady-state levels of biogenesis-related transcription factors (e.g. mitochondria transcription factor A, mitochondrial transcription specificity factors, nuclear respiratory factors 1 and 2, and peroxisome proliferator activated receptor gamma coactivator-1-alpha), mtDNA-encoded transcripts and proteins, and rates of mitochondria translation. These techniques are described in isolation and in the context of transgenic and dietary animal models that have been used as tools to study the regulation of mitochondria biogenesis and its role in disease pathology.


Polysomnographic pattern recognition for automated classification of sleep-waking states in infants.
A robust, automated pattern recognition system for polysomnography data targeted to the sleep-waking state and stage identification is presented. Five patterns were searched for: slow-delta and theta wave predominance in the background electro-encephalogram (EEG) activity; presence of sleep spindles in the EEG; presence of rapid eye movements in an electro-oculogram; and presence of muscle tone in an electromyogram. The performance of the automated system was measured indirectly by evaluating sleep staging, based on the experts' accepted methodology, to relate the detected patterns in infants over four months of post-term age. The set of sleep-waking classes included wakefulness, REM sleep and non-REM sleep stages I, II, and III-IV. Several noise and artifact rejection methods were implemented, including filters, fuzzy quality indices, windows of variable sizes and detectors of limb movements and wakefulness. Eleven polysomnographic recordings of healthy infants were studied. The ages of the subjects ranged from 6 to 13 months old. Six recordings counting 2665 epochs were included in the training set. Results on a test set (2,369 epochs from five recordings) show an overall agreement of 87.7% (kappa 0.840) between the automated system and the human expert. These results show significant improvements compared with previous work.


Isolation and structural analysis of efficient autonomously replicating sequences (ARSs) of the yeast Candida utilis.
The industrially important yeast Candida utilis is widely used in production of food and medical materials, but its host-vector system has not been well developed. We screened for compact and efficient ARSs to construct practically useful vectors. The C. utilis strain AHU3053 was found to be efficiently transformed by the conventional lithium acetate method and was used as the host. The C. utilis IAM4264 genomic library was constructed by inserting the partial Sau3AI digests in pRI51, which has a kanMX gene expressible in C. utilis. By examining 98 C. utilis G418-resistant transformants, five plasmids had the highest ARS activity. By trimming of the inserts, the 1490 and 552 bp fragments with transformation activity of over 10(3)/microg DNA were obtained from ARS3 and ARS4, respectively. Although several sequences identical to S. cerevisiae ARS consensus sequences (ACSs) were found in ARS3 and ARS4, our deletion analysis indicated that these were not essential for the activity. Because the minimal functional ARS fragment was also several-fold larger than that of S. cerevisiae, the C. utilis ARSs have some unique characteristics resembling the Sz. pombe ARSs. These ARSs were functional in other C. utilis strains tested and useful for constructing practical vectors.


The dynamic lung microbiome in health and disease.
New methods and technologies within the field of lung biology are beginning to shed new light into the microbial world of the respiratory tract. Long considered to be a sterile environment, it is now clear that the human lungs are frequently exposed to live microbes and their by-products. The nature of the lung microbiome is quite distinct from other microbial communities inhabiting our bodies such as those in the gut. Notably, the microbiome of the lung exhibits a low biomass and is dominated by dynamic fluxes of microbial immigration and clearance, resulting in a bacterial burden and microbiome composition that is fluid in nature rather than fixed. As our understanding of the microbial ecology of the lung improves, it is becoming increasingly apparent that certain disease states can disrupt the microbial-host interface and ultimately affect disease pathogenesis. In this Review, we provide an overview of lower airway microbial dynamics in health and disease and discuss future work that is required to uncover novel therapeutic targets to improve lung health.


Adult ADHD screening scores and hospitalization due to pedestrian injuries: a case-control study.
The aim of this study was to investigate the association between adult ADHD screening scores and hospitalization due to pedestrian injuries in a sample of Iranian pedestrians. Through a case-control study, a case population of 177 pedestrians injured by the vehicles in road traffic crashes were compared with 177 controls who lacked a record of intentional or unintentional injuries enrolled from various wards of Imam Reza University Hospital which is a specialty teaching hospital located in the same city with similar referral level. The cases and controls had an age range of 18-65 years and were matched on gender and age. ADHD symptom profile was assessed using the Persian Self-report Screening Version of the Conner's Adult ADHD Rating Scales (CAARS-S:SV). The association of ADHD screening score and pedestrian injuries was investigated using multiple binary logistic regression to investigate the independent effect of ADHD index score on belonging to case group. Both crude and adjusted odds ratios were reported. Men comprised 86.4% of the study subjects. The crude odds ratios for all the four ADHD subscales to be associated with pedestrian injuries were 1.05, 1.08, and 1.04 for the subscales A (attention deficit), B (hyperactivity/impulsiveness) and ADHD index respectively. However, the association for subscale A was not statistically significant with a borderline p-value. The final multivariate analysis showed that variables associated with pedestrian injuries in the road traffic crashes were ADHD Index score (OR = 1.06, 95% CI: 1.01-1.12); economic status (including household income and expenditure capacity); educational level and total walking time per 24 h. Adult ADHD screening score can predict pedestrian injuries leading to hospitalization independently from sex, age, economic status, educational level and pedestrian exposure to traffic environment (average walking time).


Origin of the phosphate at the ligation junction produced by self-splicing of Tetrahymena thermophila pre-ribosomal RNA.
The exons of the self-splicing pre-ribosomal RNA of Tetrahymena thermophila are joined accurately in vitro, even when only 33 nucleotides of the natural 5' exon and 38 nucleotides of the natural 3' exon remain. RNA fingerprint analysis was used to identify the unique ribonuclease T1 oligonucleotide generated by exon ligation. Secondary digests of the ligation junction oligonucleotide with ribonuclease A confirmed the identity of the fragment and demonstrated that the phosphate group that forms the phosphodiester bond at the ligation junction is derived from the 5' position of a uridine nucleotide in the RNA. This observation supports the prediction that the splice junction phosphate is derived from the 3' splice site. These results emphasize the mechanistic similarities of RNA splicing reactions of the group I introns, group II introns and nuclear pre-mRNA introns.


The Need for Biological Countermeasures to Mitigate the Risk of Space Radiation-Induced Carcinogenesis, Cardiovascular Disease, and Central Nervous System Deficiencies.
NASA's currently planned long-duration, deep space exploration missions outside of low Earth orbit (LEO) will result in the exposure of astronauts to relatively high lifetime doses of ionizing radiation (IR), exceeding what humans have previously encountered in space. Of concern to this exposure are the long-term health consequences of radiation carcinogenesis, cardiovascular and degenerative disease, and central nervous system decrements. Existing engineering solutions are insufficient to decrease the lifetime accumulated IR exposure to levels currently allowable by agency standards, therefore appropriate countermeasure and mitigation strategies must be developed to enable long duration missions. Emerging discoveries in the fields of radiation oncology and the mitigation of Acute Radiation Syndrome (ARS) have demonstrated the potential for compound-based/biological radiomodifiers to drastically improve clinical outcomes and represent a promising strategy for space radiation countermeasure development. This review outlines the unique challenges posed by the space radiation environment, defines the limits of terrestrial radiation protection strategies in space, describes a brief overview of current space radiation countermeasure development strategies, highlights potential new approaches for countermeasure identification and development, and speculates on the potential benefits beyond space exploration.


Surgery, cancer and mortality among patients with ulcerative colitis diagnosed 1962-1987 and followed until 2017 in a Danish population-based inception cohort.
Long-term data on the natural disease course of unselected patients with ulcerative colitis (UC) are limited. To determine the long-term course and prognosis of UC, including patients' risks of surgery, cancer and mortality, in a population-based cohort followed for over 50 years METHODS: All incident patients with UC diagnosed between 1962 and 1987 in Copenhagen County, Denmark were included in a population-based cohort. We extracted information about IBD-related surgeries, cancers and mortality from patient files from 1962 to 1987, and from the Danish National Patient Registry, Cancer Registry, and Register of Causes of Death during 1988-2017. Patients were matched with up to 50 individuals from the general population. We followed 1161 patients for a median of 34 years (range: 0.1-56.0). Median age at diagnosis was 33 years (range: 2-88). The cumulative probability of colectomy 10, 20, 30, 40 and 50 years after diagnosis was 22% (95% CI: 20%-25%), 27% (95% CI: 25%-30%), 31% (95% CI: 28%-34%), 34% (95% CI: 31%-37%), and 40% (95% CI: 36%-44%), respectively. The risk of small intestinal, colon, rectal and anal cancer was higher than among controls, as was cancer of the skin, pancreas and thyroid. All-cause mortality was lower than controls (adjusted RR: 0.90, 95% CI: 0.82-0.99). In this population-based cohort of UC patients diagnosed between 1962 and 1987, 40% underwent colectomy within 50 years of diagnosis. Physicians need to be aware that UC patients are at increased risk of intestinal and extra-intestinal cancers. However, UC patients' risk of mortality is comparable to that of the background population.


Differential labelling of afferents to thalamic centromedian-parafascicular nuclei with [3H]choline and D-[3H]aspartate: further evidence for transmitter specific retrograde labelling.
Microinjections of [3H]choline into the rat centromedian-parafascicular nuclei resulted in retrograde labelling of medium sized neurons in brainstem areas considered to comprise the origin of cholinergic innervation; the ipsilateral pedunculopontine tegmental, laterodorsal tegmental and parabrachial nuclei, and, bilaterally, in bulbar reticular formation. In contrast, D-[3H]aspartate labelled the origin of the corticothalamic input, which is believed to use glutamate and/or aspartate as transmitter. In addition, D-[3H]aspartate labelled smaller cells in mesencephalic and pontine periventricular gray, and parabrachial nuclei. It was concluded that retrograde labelling with [3H]choline and D-[3H]aspartate are selective phenomena with specificity for cholinergic and acidic amino acid connections, although occasional labelling of substantia nigra neurons with [3H]choline indicated that unspecific labelling may occur.


Severe atherosclerosis in rheumatoid arthritis and hyperhomocysteinemia: is there a link?
Rheumatoid arthritis (RA) is a chronic inflammatory joint disease whose main complication is accelerated atheroma responsible for high rates of cardiovascular morbidity and mortality. Hyperhomocysteinemia is among the factors incriminated in RA-associated atheroma. We managed a 46-year-old patient with RA who required admission to evaluate severe arterial and venous disease with involvement of the coronary, renal, and peripheral arteries. She had no laboratory evidence of rheumatoid vasculitis or conventional cardiovascular risk factors (diabetes and hypercholesterolemia) and had never smoked. Her serum homocysteine level was elevated to 20.9 micromol/L as a result of a homozygous C667T mutation in the methylenetetrahydrofolate (MTHFR) gene. Folate and vitamin B12 levels were normal. A circulating anticoagulant was identified. Hyperhomocysteinemia, which is defined as a homocysteine level greater than 15 micromol/L, is a risk factor for arterial and venous disease. Hyperhomocysteinemia is found in 20%-42% of patients with RA. Methotrexate therapy is the most common causative factor. Other causes include MTHFR deficiency, vitamin B12 deficiency, renal failure, old age, and smoking. Whatever the underlying cause, folic acid supplementation returns the homocysteine level to normal.


The exchange of health and performance information when transitioning from club to National football teams: A Delphi survey of National team practitioners.
To establish agreement in National team contexts when players transition from club to National team about (i) what medical and physical information to collect, (ii) how to use information (iii) identifying challenges to collection and (iv) collection methods. Delphi survey. A series of sequential online questionnaires were sent to heads of medical and performance of the 32 National teams following the FIFA 2018 World Cup. Two separate Delphi's; 'Medical' and 'Physical' were administered. The 'Medical' respondent was the person responsible for player health. 'Physical' referred to the person responsible for physical performance. Content analyses were performed, with subsequent rounds designed according to responses of the previous. Agreement was considered at ≥70%. Twenty-three Medical (72%) and 14 (44%) Physical heads participated in Round 1 (3 rounds total). Seventeen Medical and 12 Physical respondents completed all rounds. Medical information agreed upon injury epidemiology, screening and injury treatment strategies. Physical information included training/match-loads, fatigue, wellness and current exercise programmes. Both Medical and Physical agreed information should be used to plan and individualise player programmes. Additionally medical information should guide coaches' national team selection. Communication, willingness to share and quality/completeness of information were agreed as main challenges. Medical and Physical respondents agreed a standardised reporting form and electronic shared database as best option to collect information. Our findings highlight the importance of health and performance information exchange between national and club teams. Further, this exchange should be cooperative, symbiotic and a two-way process to assist with improving player health.


A triple distinction of cerebellar function for oculomotor learning and fatigue compensation.
The cerebellum implements error-based motor learning via synaptic gain adaptation of an inverse model, i.e. the mapping of a spatial movement goal onto a motor command. Recently, we modeled the motor and perceptual changes during learning of saccadic eye movements, showing that learning is actually a threefold process. Besides motor recalibration of (1) the inverse model, learning also comprises perceptual recalibration of (2) the visuospatial target map and (3) of a forward dynamics model that estimates the saccade size from corollary discharge. Yet, the site of perceptual recalibration remains unclear. Here we dissociate cerebellar contributions to the three stages of learning by modeling the learning data of eight cerebellar patients and eight healthy controls. Results showed that cerebellar pathology restrains short-term recalibration of the inverse model while the forward dynamics model is well informed about the reduced saccade change. Adaptation of the visuospatial target map trended in learning direction only in control subjects, yet without reaching significance. Moreover, some patients showed a tendency for uncompensated oculomotor fatigue caused by insufficient upregulation of saccade duration. According to our model, this could induce long-term perceptual compensation, consistent with the overestimation of target eccentricity found in the patients' baseline data. We conclude that the cerebellum mediates short-term adaptation of the inverse model, especially by control of saccade duration, while the forward dynamics model was not affected by cerebellar pathology.


Chemical constituents of green teas processed from albino tea cultivars with white and yellow shoots.
Green tea processed from albino tea varieties often has umami taste and fresh aroma. This study identified green teas made from two types of albino tea cultivar, one having the white shoots (called Naibai, NB) and the other having the yellow shoots (called Huangjinya, HJY). Taste compounds analyses showed that galloylated catechins were highly concentrated in HJY green teas, whereas non-galloylated catechins and amino acids were more abundant in NB green teas. CsTA (involved in the catabolism of galloylated catechins) showed high expression in HJY tea shoots, resulting in gallic acid as a precursor for β-glucogallin biosynthesis being abundant in HJY. CsPDX2.1 (responsible for theanine hydrolyzation) had a lower expression level in NB than HJY shoots. Fatty acid-derived volatiles (FADVs), glycosidically bound volatiles (GBVs) and carotenoid-derived volatiles (CDVs) were highly concentrated in HJY green teas, whereas amino acids-derived volatiles were highly concentrated in NB green teas.


Background concentrations of lead and cadmium in the lichen Hypogymnia physodes at different altitudes.
The background concentrations of lead and cadmium in the epiphytic lichen Hypogymnia physodes were determined and found to depend on altitude. The lead content increases linearly with increasing altitude, whereas the cadmium content increases up to altitudes of 900-1100 m, and then decreases above this height.


Fecal tumor necrosis factor-alpha and calprotectin as differential diagnostic markers for severe diarrhea of small infants.
The etiology of early-onset diarrhea of neonates and small infants that persists despite bowel rest is heterogeneous. Two different categories of disorders presenting with diarrhea in the first weeks of life can be distinguished: constitutive intestinal epithelial disorders (microvillus atrophy [MVA] or epithelial dysplasia [ED]) and immune-inflammatory disorders, (autoimmune enteropathy [AIE] or inflammatory colitis [IC]). We aimed to evaluate in a prospective manner the use of fecal inflammatory markers in the differential diagnosis of severe persistent diarrhea. Twenty-five patients (17 males) were enrolled in this study (median age 8 months). Fourteen children had a constitutive enterocyte disorder (group 1: MVA = 8, ED = 6), and 11 patients had an immuno-inflammatory disease (group 2: AIE = 5, IC = 6). Stool samples were collected at the time of diagnosis and stored at -80 degrees until tumor necrosis factor (TNF)-alpha and calprotectin were measured by enzyme-linked immunoadsorbent assay. No significant differences in age at onset of diarrhea or in stool volumes were observed between both groups. In group 1, fecal TNF-alpha was undetectable/normal in 14 of 14 children, whereas group 2 showed dramatically elevated TNF-alpha levels (mean 3,104, range 237-18,078 pg/g) in 8 of 11 patients. Similarly, calprotectin levels were undetectable/normal in 14 of 14 patients in group 1 and highly raised in 11 of 11 patients in group 2 (median 1,145, range 375-3,095 mug/g), P < 0.01. Under therapy, these inflammatory parameters normalized. Determination of fecal inflammatory markers is a simple method helping to distinguish constitutive from immuno-inflammatory etiologies of severe persistent diarrhea. These data also suggest that constitutive enterocyte disorders are not accompanied by an inflammatory mucosal reaction.


Conservative management of a perianal rhabdomyosarcoma in a 2-year old child by Papillon's technique.
Rhabdomyosarcoma (RMS) is the most common sarcoma in paediatric patients. A perianal site is unusual and is associated with a low cure rate. The few cases of reported perianal RMS have been associated with sequelae. Here, we report the case of a 29-month-old male child who received sequential treatment by surgery, chemotherapy and radiotherapy inspired by Papillon's irradiation of adult anal/low-rectum cancers (including external beam radiotherapy in the gynecological exam position followed by brachytherapy) and who remains in complete remission 49 months post treatment with no sphincter or other anorectal disorders.


In vivo Monitoring and Assessment of Exogenous Mesenchymal Stem Cell-Derived Exosomes in Mice with Ischemic Stroke by Molecular Imaging.
Mesenchymal stem cell-derived exosomes (MSC-exos) are considered an important restorative treatment for ischemic stroke. However, the migration ability and survival of exogenous MSC-exos remain unclear. Here, we investigated whether MSC-exos migrate into the ischemic brain and play a protective role against ischemic stroke. MSC-exos labeled with DiR were injected intravenously into mice with ischemic stroke. Near-infrared fluorescence (NIRF) images were obtained on days 0, 1, 3, 5, 7, 10, and 14, and magnetic resonance (MR) images were obtained on days 1, 7 and 14. On day 14, the functional outcomes, angiogenesis, neurogenesis, and white matter remodeling were assessed, and Western blot assays were performed. Fluorescence signals from the MSC-exos appeared in the injured brain from day 1 and peaked on day 3. The immunofluorescence staining of the brain samples revealed that the MSC-exos were localized in neurons. The behavioral scores and T2-weighted imaging indicated that the MSC-exos improved neurological functional recovery after stroke. In addition, the in vivo MR-diffusion tensor imaging (DTI) indicated that the exogenous MSC-exos increased the fractional anisotropy (FA) value, fiber length, and fiber number ratio. Furthermore, in the mice with ischemic stroke treated with MSC-exos, angiogenesis and neurogenesis were significantly improved, and the expression of IL-1β was reduced. MSC-exos can migrate into the brains of mice with ischemic stroke and exert therapeutic effects against ischemic stroke; therefore, MSC-exos may have broad clinical applications in the future.


Nephron Progenitor But Not Stromal Progenitor Cells Give Rise to Wilms Tumors in Mouse Models with β-Catenin Activation or Wt1 Ablation and Igf2 Upregulation.
Wilms tumor, a common childhood tumor of the kidney, is thought to arise from undifferentiated renal mesenchyme. Variable tumor histology and the identification of tumor subsets displaying different gene expression profiles suggest that tumors may arise at different stages of mesenchyme differentiation and that this ontogenic variability impacts tumor pathology, biology, and clinical outcome. To test the tumorigenic potential of different cell types in the developing kidney, we used kidney progenitor-specific Cre recombinase alleles to introduce Wt1 and Ctnnb1 mutations, two alterations observed in Wilms tumor, into embryonic mouse kidney, with and without biallelic Igf2 expression, another alteration that is observed in a majority of tumors. Use of a Cre allele that targets nephron progenitors to introduce a Ctnnb1 mutation that stabilizes β-catenin resulted in the development of tumors with a predominant epithelial histology and a gene expression profile in which genes characteristic of early renal mesenchyme were not expressed. Nephron progenitors with Wt1 ablation and Igf2 biallelic expression were also tumorigenic but displayed a more triphasic histology and expressed early metanephric mesenchyme genes. In contrast, the targeting of these genetic alterations to stromal progenitors did not result in tumors. These data demonstrate that committed nephron progenitors can give rise to Wilms tumors and that committed stromal progenitors are less tumorigenic, suggesting that human Wilms tumors that display a predominantly stromal histology arise from mesenchyme before commitment to a stromal lineage.


Total and differential white blood cell count in cannabis users: results from the cross-sectional National Health and Nutrition Examination Survey, 2005-2016.
Elevated white blood cell (WBC) count in tobacco cigarette smokers compared to non-smokers has been well documented, but little is known on circulating WBC counts and cannabis use. The National Health and Nutrition Examination Survey (2005-2016) is designed to be nationally representative of United States non-institutionalized population. The current study includes adult participants 20-59 years of age (n= 16,430) who underwent a detailed examination in the mobile examination center (MEC). Cannabis use was measured using Audio Computer-Assisted Self-Interview. Cannabis use was classified into never, former, occasional (1-7 days of the past 30 days), and heavy (>7 days of the past 30 days). WBC count was measured using the Coulter Counter method. Total WBC count was higher among heavy cannabis users when compared to never users (β = 189; 95% confidence interval: 74, 304, p = 0.001). Among circulating WBC types, modest differences were observed for neutrophil count. Neither former nor occasional cannabis use was associated with total or differential WBC counts. A modest association between heavy cannabis use and WBC count was detected. Additional research is needed to understand the immune related effects of different modes of cannabis use and to elucidate the role of proinflammatory chemicals generated from smoking cannabis.


Inducible atrial flutter after the Mustard repair of complete transposition of the great arteries.
Atrial flutter is a common postoperative arrhythmia in patients with complete transposition of the great arteries (d-TGA) after the Mustard repair. Sixty patients with d-TGA who had the Mustard repair were evaluated by electrophysiologic studies. Thirty-three (55%) had inducible sustained atrial flutter; 17 of them developed spontaneous clinical episodes of atrial flutter (clinical atrial flutter group) and 16 did not (nonclinical atrial flutter group). In 6 of the 17 patients (35%) with clinical inducible atrial flutter, the condition was first documented in the electrophysiologic laboratory with subsequent development of spontaneous clinical episodes. Catheter endocardial mapping, used to determine atrial activation sequences and and conduction intervals, revealed intraatrial conduction delays with late activation of the low atrial sites in all patients. Abnormalities of atrial refractoriness were present, with a greater dispersion of atrial refractoriness found in the clinical atrial flutter group. Severe abnormalities of sinus nodal function appeared to a significantly greater degree among patients who had clinical episodes of atrial flutter. These electrophysiologic abnormalities and associated arrhythmias may predispose patients with d-TGA to sudden death.


Neonatal monosodium glutamate treatment causes obesity, diabetes, and macrovesicular steatohepatitis with liver nodules in DIAR mice.
Non-alcoholic steatohepatitis (NASH) is the hepatic manifestation of metabolic syndrome (MS). Monosodium glutamate (MSG)-treated ICR mice is a useful model of MS and NASH, but it shows the different patterns of steatosis from human NASH. Because inbred aged DIAR (ddY, Institute for Animal Reproduction) mice spontaneously show the similar pattern of steatosis as NASH, we analyzed their liver pathology after administering MSG. MSG-treated DIAR mice (DIAR-MSG) and untreated DIAR mice (DIAR-controls) were sacrificed and assessed histopathologically at 29, 32, 40, 48, and 54 weeks of age. The NASH activity score, body mass index, blood glucose level, and oral glucose tolerance test were also assessed. The body mass index and blood glucose levels of DIAR-MSG were significantly higher than controls. The oral glucose tolerance test revealed a type 2 diabetes pattern in DIAR-MSG. The livers of DIAR-MSG mice showed macrovesicular steatosis, lobular inflammation with neutrophils, and ballooning degeneration after 29 weeks. At 54 weeks, mild fibrosis was observed in 5/6 DIAR-MSG and 2/5 DIAR-control mice. In imaging mass spectrometry analysis, cholesterol as well as triglyceride accumulated in the liver of DIAR-MSG mice. Atypical liver nodules were also observed after 32 weeks in DIAR-MSG, some with cellular and structural atypia mimicking human hepatocellular carcinoma. The NASH activity score of DIAR-MSG after 29 weeks was higher than that of control mice, suggesting the development of NASH. DIAR-MSG had NASH-like liver pathology and liver nodules typically associated with MS symptoms. DIAR-MSG provides a valuable animal model to analyze NASH pathogenesis and carcinogenesis.


Properties of voltage-gated ion channels formed by syringomycin E in planar lipid bilayers.
Using the planar lipid bilayer technique we demonstrate that the lipodepsipeptide antibiotic, syringomycin E, forms voltage-sensitive ion channels of weak anion selectivity. The formation of channels in bilayers made from dioleoylglycerophosphatidylserine doped with syringomycin E at one side (1-40 micrograms/ml) was greatly affected by cis-positive voltage. A change of voltage from a positive to a negative value resulted in (i) an abrupt increase in the single channel conductance (the rate of increase was voltage dependent) simultaneous with (ii) a closing of these channels and an exponential decrease in macroscopic conductance over time. The strong voltage dependence of multichannel steady state conductance, the single channel conductance, the rate of opening of channels at positive voltages and closing them at negative voltages, as well as the observed abrupt increase of single channel conductance after voltage sign reversal suggest that the change of the transmembrane field induces a significant rearrangement of syringomycin E channels, including a change in the spacing of charged groups that function as voltage sensors. The conductance induced by syringomycin E increased with the sixth power of syringomycin E concentration suggesting that at least six monomers are required for channel formation.


Tuberculosis dissemination in kidney transplant recipient treated with anti-CD40 monoclonal antibody: a case report.
Tuberculosis (TBC) in solid organ transplant recipients represents a severe complication. The incidence among transplant recipients is higher than in the general population, and the diagnosis and treatment remain challenging. We present a case of active disseminated tuberculosis in a kidney transplant recipient treated with an anti-CD40 monoclonal antibody, who had been previously exposed to an active form of the disease, but latent tuberculosis (LTBI) was repeatedly ruled out prior to transplantation. To the best of our knowledge, no other case has been reported in a patient treated with the anti-CD40 monoclonal antibody. A 49-year-old patient, 1.5 years after primary kidney transplantation, presented with vocal cord problems, a dry irritating cough, and a sore throat. A detailed investigation, including a high-resolution chest CT scan, revealed the diagnosis of disseminated tuberculosis. The antituberculosis treatment consisting of rifampicin, isoniazid, pyrazinamide, and ethambutol was started immediately. The patient's condition became complicated by relapsing diarrhoea. The colonoscopy revealed a circular stenosis above Bauhin's valve. Microscopical findings showed active colitis and vaguely formed collections of epithelioid macrophages without fully developed caseous granulomas and were consistent with the clinical diagnosis of tuberculosis. The antituberculosis treatment was subsequently enhanced by moxifloxacin and led to a great improvement in the patient's condition. In this case, false negativity of interferon-γ release assays and possibly higher risk for intracellular infections in patients on costimulatory signal blockers are discussed.


Mental health and suicidality in Afghan students after the Taliban takeover in 2021.
On the 15th of August 2021, Kabul was captured by the Taliban, leading to the fall of the Islamic Republic of Afghanistan. The present study investigated PTSD symptoms, depression, suicide risk and facets of positive mental health in the immediate aftermath of the Taliban take-over. A total of 214 Afghan university students (73.7% women; age in years: M(SD) = 23.92 (5.77)) took part in this cross-sectional study between August and November 2021. Self-report measures of PTSD, depression, suicide ideation/behavior, positive mental health, social support, and posttraumatic growth were used. Severe posttraumatic stress disorders symptoms were reported by 70%, clinically relevant depression symptoms were reported by 69.7% and significant suicide ideation/behavior was reported by 38.6% of the sample. Posttraumatic growth moderated the impact of depression on suicide risk. No interaction effects were found for positive mental health and social support. The study focused on a specific group of highly educated and predominantly female Afghan students limiting the generalizability of the findings. PTSD symptoms, depression and suicidality show an alarmingly high prevalence in this specific sample of Afghan students. Various protective factors seem to be insufficient to buffer the association between PTSD, depression and suicide risk.


Anomalous vitamin E effects in mitochondrial oxidative metabolism.
Three different vitamin E effects, suggestive of specific antioxidant effects, were discovered in the protective action of vitamin E against respiratory decline (a decrease in mitochondrial respiration attributed to a "leakage" of electron transport radicals). No correlation was found between respiraotry decline and random lipid peroxidation. The mechanisms behind two of the three atypical vitamin E effects were defined. Both involve an artifact in the TBA assay for lipid peroxidation. This artifact occurs when TBA assays are carried out in the presence of sucrose and acetaldehyde; the latter is produced from ethanol, the solvent used to add vitamin E to preparations. The artifact in the TBA assay for peroxidations appears also to be responsible for differing interpretations of the hepatotoxic effect of ethanol.


Finding Balance with Music: Music Therapy as a Tool for Recovery and Increasing Welfare for Orphans of COVID-19 Victims.
Music therapy can effectively address children's psychological, emotional, cognitive, and social needs. Music therapy can provide a safe and supportive environment for children to process their emotions and deal with the grief of losing a parent.


The Analgesic Efficacy of Transversus Abdominis Plane Block After Bariatric Surgery: a Systematic Review and Meta-analysis with Trial Sequential Analysis.
The transversus abdominis plane (TAP) block has been used to relieve pain after bariatric surgery but with conflicting data on its analgesic efficacy. We conducted this systematic review and meta-analysis with trial sequential analysis to clarify whether TAP block provides effective postoperative analgesia in patients undergoing bariatric surgery. We systematically searched the literature for any trials comparing TAP block with a control group (no block or sham injection). The primary outcome was pain scores at rest (analog scale, 0-10) at 2 postoperative hours. Secondary pain-related outcomes included pain scores at rest at 12 and 24 h and both dynamic pain scores and intravenous morphine equivalent consumption at 2, 12 and 24 h. Additional secondary outcomes sought were rates of postoperative infection, haematoma, visceral injury and local anaesthetic systemic toxicity. Thirteen trials totalling 1025 patients were identified. Pain scores at rest at 2 postoperative hours were significantly lower in the TAP block group compared with the control group, with a mean (95% CI) difference of - 1.8 (- 2.5, - 1.1); I2 = 85%; p < 0.00001. All other secondary pain-related outcomes were also significantly lower in the intervention group with the exception of dynamic pain scores and intravenous morphine equivalent consumption at 2 postoperative hours. Rates of block-related complications were not significantly different between groups. The overall quality of evidence was moderate-to-low. There is moderate-to-low level evidence that the TAP block improves postoperative analgesia after bariatric surgery up to 24 postoperative hours, when compared with a control group, without major reported complications. Clinical Trial NumberPROSPERO - registration number: CRD42019136542.


Revisiting the antidepressant-like effects of desipramine in male and female adult rats: sex disparities in neurochemical correlates.
The preclinical antidepressant-like characterization of desipramine relied almost exclusively in male rodents, with only a few contradictory reports done in females. Given that most experiments assessed a single dose and/or timepoint of analysis after-treatment, this study evaluated potential sex-differences in the length of the antidepressant-like response induced by different doses of desipramine as well as the molecular underpinnings driving the different responses by sex. Male and female Sprague-Dawley rats were treated (i.p.) with 3 pulses of desipramine (5, 10 or 20 mg/kg) or vehicle (0.9% NaCl) within 24 h. The antidepressant-like effects were evaluated in the forced-swim test 1-h, 1- and 3-day post-treatment. The rate of cell proliferation and the regulation of key neuroplasticity markers (FADD, Cdk5, p35, p25) involved in antidepressant-like responses in the hippocampus were evaluated 1-h, 1-day and 5-day post-treatment. Desipramine induced similar antidepressant-like effects in male and female rats (effective doses of 10 and 20 mg/kg, with effects that lasted up to 1-day post-treatment), without altering the rate of cell proliferation. However, some sex-differences emerged when evaluating neuroplasticity markers in the hippocampus, while no changes were observed for female rats, desipramine regulated FADD, Cdk-5 and p25 in males in a way that suggested neuroprotective actions. Our findings imply that while desipramine induced similar antidepressant-like responses for male and female rats, some differences emerged in the regulation of certain neuroplasticity markers, suggesting that distinctive molecular mechanisms might be participating in the therapeutic response of desipramine for both sexes.


Extradural analgesia in the intrapartum management of a patient with pulmonary hypertension.
We describe the intrapartum management of a patient with severe pulmonary hypertension using extradural analgesia with a low dose of 0.125% bupivacaine and fentanyl 20 micrograms ml-1 by continuous infusion at a rate of 2.5 ml h-1. This provided effective analgesia and haemodynamic stability. The importance of continuous direct measurement of pulmonary artery pressure is emphasized.