Phylogenetic relationships of filamentous sulfur bacteria (Thiothrix spp. and Eikelboom type 021N bacteria) isolated from wastewater-treatment plants and description of Thiothrix eikelboomii sp. nov., Thiothrix unzii sp. nov., Thiothrix fructosivorans sp. nov. and Thiothrix defluvii sp. nov.
The relationship of mixotrophic and autotrophic Thiothrix species to morphologically similar chemoorganotrophic bacteria (e.g. Leucothrix species, Eikelboom type 021N bacteria) has been a matter of debate for some years. These bacteria have alternatively been grouped together on the basis of shared morphological features or separated on the basis of their nutrition. Many of these bacteria are difficult to maintain in axenic culture and, until recently, few isolates were available to allow comprehensive phenotypic and genotypic characterization. Several isolates of Thiothrix spp. and Eikelboom type 021N strains were characterized by comparative 16S rRNA sequence analysis. This revealed that the Thiothrix spp. and Eikelboom type 021N isolates formed a monophyletic group. Furthermore, isolates of Eikelboom type 021N bacteria isolated independently from different continents were phylogenetically closely related. The 16S rRNA sequence-based phylogeny was congruent with the morphological similarities between Thiothrix and Eikelboom type 021N. However, one isolate examined in this study (Ben47) shared many morphological features with the Thiothrix spp. and Eikelboom type 021N isolates, but was not closely related to them phylogenetically. Consequently, morphology alone cannot be used to assign bacteria to the Thiothrix/type 021N group. Comparative 16S rRNA sequence analysis supports monophyly of the Thiothrix/type 021N group, and phenotypic differences between the Thiothrix spp. and Eikelboom type 021N bacteria are currently poorly defined. For example, both groups include heterotrophic organisms that deposit intracellular elemental sulfur. It is therefore proposed that the Eikelboom type 021N bacteria should be accommodated within the genus Thiothrix as a new species, Thiothrix eikelboomii sp. nov., and three further new Thiothrix species are described: Thiothrix unzii sp. nov., Thiothrix fructosivorans sp. nov. and Thiothrix defluvii sp. nov.


Serum magnesium level and cardiac valve calcification in hemodialysis patients.
Cardiac valve calcification is closely related to cardiovascular disease. The aim of this study was to investigate the magnesium level and cardiac valve calcification in hemodialysis patients. A cross-sectional study was conducted in 105 maintenance hemodialysis patients with complete follow-up data from June 2020 to May 2021 in Beijing Tsinghua Changgung Hospital, Tsinghua University. Baseline data, including sex, age, primary disease, liver and kidney function, electrolytes and parathyroid hormone, were recorded. According to their echocardiograms, patients were divided into a cardiac valve calcification group and a noncardiac valve calcification group, and the correlations between valve calcification and clinical data were analyzed. Of 105 patients under hemodialysis, 60 (56.6%) were male, with an average age of 62.1 ± 13.5 years and a mean dialysis duration of 58.8 ± 45.4 months. The majority of primary renal diseases were diabetic nephropathy (55, 51.9%). Approximately 64.8% of the 105 maintenance hemodialysis patients had cardiac valve calcification, and 35.2% were in the noncardiac valve calcification group. The independent t test and the chi-square test analysis showed that the cardiac valve calcification group had older age, higher smoking rate, diabetes mellitus, lower extremity arterial occlusion, coronary heart disease, and coronary artery calcification ratio but lower parathyroid hormone, serum calcium, serum magnesium, albumin, prealbumin, and high-density lipoprotein cholesterol levels (P < 0.05). Logistic regression analysis showed that age, diabetes mellitus, coronary artery calcification, lower serum magnesium, lower serum calcium, and lower parathyroid hormone levels were associated with valve calcification. The presence of cardiac valve calcification was associated with age, calcium, phosphorus and lower magnesium level. These factors we should pay more attention in clinical practice.


Capture and display mismatch compensation for real-time digital holographic interferometry.
Optical holographic interferometry (HI) is realized by two well-known techniques: double exposure holographic interferometry (DEHI) and real-time holographic interferometry (RTHI). However, the digital version of HI is typically realized numerically by DEHI. The main problem in digital implementation of RTHI is the lack of commercially available cameras and spatial light modulators with the same pixel size. This mismatch results in lateral and transversal magnifications of an object wavefront reconstruction. In real-time digital HI the reconstruction of an object in an initial state has to be superimposed on top of the loaded object. In this work, we present and analyze five approaches to overcome the mismatch problem, and the performance of these procedures is numerically quantified and compared. The experimental suitability of these approaches is investigated.


[The use of cottage hospitals' beds in Nordkapp].
An analysis was made of 414 admissions during a one-year period to three general practitioner beds. Within the first day, 20% of the patients were discharged, while 22% were transferred to the main hospital after examination and primary treatment. 58% stayed more than one day. The mean stay was 5.0 days. The three major groups of medical conditions according to the International Classification of Primary Care were cardiovascular diseases, diseases of the musculoskeletal system and diseases of the lungs and the respiratory tract. Patients > or = 60 years of age constituted 55.8% of the total, taking up 80.6% of total bed days. In the age group > or = 80 years of age, there were three admissions for every five inhabitants, while two in five had one or more hospital stay. 65% of all patients (15.7%) had two stays or more, taking up a total of 60.5% of total bed days. Using the general practitioner beds as a low threshold service proved especially useful with patients suffering from heart failure, asthma or chronic obstructive lung disease. The beds had a key function in the rehabilitation of the elderly, in the care of cancer patients, and in terminal care. They were of basic importance to the organisation of daily emergencies.


Biaxial hyperbolic metamaterials using anisotropic few-layer black phosphorus.
Most of hyperbolic metamaterials (HMMs) investigated to date are based on isotropic materials resulting in uniaxial HMMs in which dielectric permittivities perpendicular to the propagation direction are the same. Using an anisotropic material constituent to form a HMM is a promising research direction providing opportunities to control the dielectric permittivity in all three directions independently. Herein, we propose and theoretically demonstrate novel biaxial HMMs composed of multilayer stacks of few-layer black phosphorus (BP) and Au thin films. Black phosphorus is an anisotropic material exhibiting crystal axis-dependent dielectric permittivity due to its puckered crystal structure. The proposed HMM provides previously unattained hyperbolic dispersion relations in which the dielectric permittivity in Z-direction of the structure shows opposite sign from that in X- and Y-directions in the most wavelengths from 400~900nm. Furthermore, we calculated the Purcell factor of the proposed biaxial HMMs using full-field electromagnetic simulations.


[Carbon band implants in animal experiments. Light and transmission electron microscopy studies of biocompatibility].
Part of the patella ligament was resected in rabbits and replaced by carbon fibre implants. After 1, 2, 3, 6 weeks, 3 and 12 months carbon implants with surrounding tissues as well as iliac lymph nodes were removed and examined by light- and transmission electron microscopy. Of special interest were the questions whether the carbon fibre implant, will be removed by phagocytosis and substituted by a new ligament or a adequate repair tissue? Our light- and transmission electron microscopic studies give no indication of successful removal of carbon fibres by phagocytosis. The carbon fibre implant was surrounded by dense connective tissue like a scar. In deep layers of the carbon implant was no vital dense or regular connective tissue, even not after 3 and 12 months. There is no replacement of the carbon fibre implant by a new ligament or tendon but a persistent foreign body reaction. With regard to these results it is very doubtful if good late results with ligament and tendon replacement by carbon fibre implants can be expected in patients.


Reliability and validity of a Nepalese version of the Kiddo-KINDL in adolescents.
The objective of this study was to assess the reliability and validity of a Nepalese version of the Kiddo-KINDL to measure Health-Related Quality of Life (HRQOL) in adolescents. We collected data from 204 students between 13 to 16 years old from four secondary schools in Lalitpur district, Nepal. The students answered a Nepalese version of the Kiddo-KINDL and the Center for Epidemiological Studies-Depression Scale (CES-D) with a self-administrated questionnaire. We conducted a test-retest study on the instrument at an interval of 10 days and then compared the Kiddo-KINDL scores between the low CES-D score group and the high CES-D score group students. The instrument showed good reliability and a small response variation. The internal consistency (Cronbach's alpha) of the total score was 0.93. Corrected item-total correlations showed that all items ranged from 0.47 to 0.79. The reproducibility was satisfactory with an Intraclass Correlation Coefficient (ICC) of 0.88-0.95. The Kiddo-KINDL scores in the low CES-D score group were significantly lower than those in the high CES-D score group students. The optimal cut-off score of the Kiddo-KINDL was estimated at 54.7, with an Area Under the Curve (AUC) score of 0.83 and both sensitivity (73.5%) and specificity (71.8%) were acceptably high. We recommended a mean change in Kiddo-KINDL total scores of 4.0 to be used to define a minimal important difference according to two-point CES-D score changes. Our results showed that a Nepalese version of the Kiddo-KINDL has internal consistency, reproducibility, responsiveness, interpretability, and discriminant validity.


The meeting of psychiatry and humanities: an overview.
Concerns regarding ethics of psychiatric research were a critical point in research when lots of news was announced about human rights abuses in the Nazi Germany. However, even nowadays, psychiatric research involving people suffering from different types of psychiatric disorders can still be distorted and, rather than fulfilling its promise of improved understanding of psychiatric disorder and its treatment, can result in serious harm to patients who participated in these investigations. This review focuses on some important ethical aspects in psychiatric research.


[Prescription of psychotherapy provided by psychologists : a new role for general practitioners ?]
This article focuses on the new model for prescribing psychotherapy provided by psychologists that has been in effect in Switzerland since July 1, 2022. Psychologists can now practice as independent providers with a prescription from a primary care physician for a given number of sessions. This new law, which should facilitate access to mental health care, introduces new administrative issues for general practitioners and transforms their relationship with their patients and psychologists. This phenomenon is part of a broader system of care that is changing and requires a great deal of adaptation on the part of front-line workers. Close collaboration between prescribing physicians, psychologists, psychiatrists and patients is therefore essential.


Cerebral edema complicating nonketotic hyperosmolar coma.
Cerebral edema as a complication of the therapy of diabetic coma has been described for over 50 years, although modern awareness dates to about 1967. Almost all cases have occurred in patients with diabetic ketoacidosis (DKA). Although a few cases of cerebral edema have been reported in patients with nonketotic hyperosmolar coma (NKHC), these are in general not well documented by either autopsy data of cat scans. Over a period of 9 years, I have encountered 5 patients who developed cerebral edema as a complication of the therapy of NKHC. The initial plasma glucose in these patients was 1,496 +/- (SD) 296 mg/dl and plasma osmolality was 382 +/- 29 mosm/kg. All had depression of sensorium to at least a stupor (stage I coma or greater). All were treated with intravenous insulin and either 77 or 154 mM NaCl, and plasma glucose fell at a mean rate of 38 mg/dl/h. In all patients, plasma glucose fell below 250 mg/dl (mean of 18 +/- 66 mg/dl) and all patients experienced increased depression of sensorium, elevated csf pressure, and brain swelling as diagnosed by cat scanning. Therapy with various combinations of glucose, mannitol and steroids were without effect. In 1 patient, insertion of a subdural intracranial screw lowered intracranial pressure from 24 to 3 cm of H2O. Three of the 5 patients died and 2 remain in a persistent vegetative state, 1 of whom is also quadriplegic.(ABSTRACT TRUNCATED AT 250 WORDS)


Randomized trial of a self-management program for primary care patients with acute low back pain: short-term effects.
We evaluated the effect of a self-management program (SMP) on primary care patients with acute low back pain (ALBP) from low income, inner city neighborhood health centers and an emergency department of a public teaching hospital. We randomized 211 primary care patients who visited a physician for ALBP (<90 days duration) to usual care or an SMP. The SMP consisted of 3 group sessions and telephone followup that focused on understanding back pain, increasing physical activity, and dealing with fears and frustrations. Of the eligible patients, 52% expressed interest in participation and 39% of all eligible patients were randomized into the study. Among patients in the treatment group, 28.3% attended at least 1 group class, 62.3% received the intervention by mail, telephone, and audiotapes, and 9.4% received no intervention. Interviewers, blinded to the treatment given, collected data at baseline and at 4 months following randomization. Compared with the control group, the intervention group reported significantly better emotional functioning (P < 0.01), increased self efficacy to manage ALBP (P = 0.03), and less fear of movement (P = 0.05) after 4 months. This SMP produced short-term improvements in emotional functioning and self efficacy to manage symptoms among patients with ALBP living in the inner city. However, methods of program delivery other than group classes are needed to reach a greater portion of the inner city patients.


Impaired Frontal-Limbic White Matter Maturation in Children at Risk for Major Depression.
Depression is among the most common neuropsychiatric disorders. It remains unclear whether brain abnormalities associated with depression reflect the pathological state of the disease or neurobiological traits predisposing individuals to depression. Parental history of depression is a risk factor that more than triples the risk of depression. We compared white matter (WM) microstructure cross-sectionally in 40 children ages 8-14 with versus without parental history of depression (At-Risk vs. Control). There were significant differences in age-related changes of fractional anisotropy (FA) between the groups, localized in the anterior fronto-limbic WM pathways, including the anterior cingulum and the genu of the corpus callosum. Control children exhibited typical increasing FA with age, whereas At-Risk children exhibited atypical decreasing FA with age in these fronto-limbic regions. Furthermore, dorsal cingulate FA significantly correlated with depressive symptoms for At-Risk children. The results suggest maturational WM microstructure differences in mood-regulatory neurocircuitry that may contribute to neurodevelopmental risk for depression. The study provides new insights into neurodevelopmental susceptibility to depression and related disabilities that may promote early preventive intervention approaches.


[Colonic pseudo-occlusion syndrome. Ogilvie's syndrome Apropos of 22 cases].
The syndrome of pseudo colonic obstruction consists of acute or subacute colonic dilatation which presents the diagnostic and therapeutic problems of any low bowel obstruction. Our experience is based on a series of 22 cases and is similar to data in the literature. There is a specific aetiological context: elderly subjects, vascular and neurological diseases, severe infection, trauma, alcoholism. The exclusion of an organic occlusion is not always an easy diagnosis and may require an exploratory laparotomy. The clinical course is dominated by the risk of diastatic perforation which carries a heavy mortality. In the majority of cases, the colonic peristalsis is restored by early diagnosis, repeated decompression with a rectal catheter, together with general measures of rehydration, control of infection and maintenance of satisfactory haemodynamic conditions. In the other cases, a draining colostomy may be required. The pathophysiological mechanism of this form of colonic ileus remains hypothetical, in which various neurogenic, vascular, toxic or metabolic factors may be involved.


Generation of human-induced pluripotent stem cells from gut mesentery-derived cells by ectopic expression of OCT4/SOX2/NANOG.
Induced pluripotent stem (iPS) cells have been generated from human somatic cells by ectopic expression of defined transcription factors. Application of this approach in human cells may have enormous potential to generate patient-specific pluripotent stem cells. However, traditional methods of reprogramming in human somatic cells involve the use of oncogenes c-MYC and KLF4, which are not applicable to clinical translation. In the present study, we investigated whether human fetal gut mesentery-derived cells (hGMDCs) could be successfully reprogrammed into induced pluripotent stem (iPS) cells by OCT4, SOX2, and NANOG alone. We used lentiviruses to express OCT4, SOX2, NANOG, in hGMDCs, then generated iPS cells that were identified by morphology, presence of pluripotency markers, global gene expression profile, DNA methylation status, capacity to form embryoid bodies (EBs), and terotoma formation. iPS cells resulting from hGMDCs were similar to human embryonic stem (ES) cells in morphology, proliferation, surface markers, gene expression, and epigenetic status of pluripotent cell-specific genes. Furthermore, these cells were able to differentiate into cell types of all three germ layers both in vitro and in vivo, as shown by EB and teratoma formation assays. DNA fingerprinting showed that the human iPS cells were derived from the donor cells, and are not a result of contamination. Our results provide proof that hGMDCs can be reprogrammed into pluripotent cells by ectopic expression of three factors (OCT4, SOX2, and NANOG) without the use of oncogenes c-MYC and KLF4.


Identification of an interaction between the m-band protein skelemin and beta-integrin subunits. Colocalization of a skelemin-like protein with beta1- and beta3-integrins in non-muscle cells.
Signaling across integrins is regulated by interaction of these receptors with cytoskeletal proteins and signaling molecules. To identify molecules interacting with the cytoplasmic domain of the beta3-integrin subunit (glycoprotein IIIa), a placental cDNA library was screened in the yeast two-hybrid system. Two identical clones coding for a 96-amino acid sequence were identified. This sequence was 100% identical to a sequence in skelemin, a protein identified previously in skeletal muscle. Skelemin is a member of a superfamily of cytoskeletal proteins that contain fibronectin-type III-like motifs and immunoglobulin C2-like motifs and that regulate the organization of myosin filaments in muscle. The amino acid residues in the isolated clones encompassed C2 motifs 4 and 5 of skelemin. A recombinant skelemin protein consisting of C2 motifs 3-7 interacted with beta1- and beta3-integrin cytoplasmic domains expressed as glutathione S-transferase (GST) fusion proteins, but not with GST-beta2-integrin cytoplasmic tail or GST alone. The skelemin-binding region was in the membrane proximal cytoplasmic domains of the integrins. Full-length skelemin interacted with integrin in intact cells as demonstrated by the colocalization of hemagglutinin-tagged skelemin in Chinese hamster ovary (CHO) cells containing alphaIIbbeta3-integrin and by the finding that microinjection of C2 motif 4 of skelemin into C2C12 mouse myoblast cells caused spread cells to round up. A skelemin-like protein was detected in CHO cells, endothelial cells, and platelets, and this protein colocalized with beta1- and beta3-integrins in CHO cells. This study suggests the presence of a skelemin-like protein in non-muscle cells and provides evidence that it may be involved in linking integrins to the cytoskeleton.


Emerging multidrug-resistant Candida species.
To describe the epidemiology, strategies for early detection, and clinical management of infections caused by the most commonly found multidrug-resistant (MDR) Candida spp. Increasing numbers of reports describing invasive infections by MDR Candida auris and Candida glabrata has been reported in medical centers worldwide. We checked all papers published along the last 10 years describing epidemiological, diagnostic, and clinical aspects of infections by MDR Candida spp., with emphasis on C. auris and C. glabrata spp. C. auris has been reported in 15 countries and multidrug resistance rates is usually above 30%. Horizontal transmission is a great concern regarding C. auris. C. glabrata ranks the second most reported Candida spp. in deep-seated infections from United States and some European Centers, although multidrug resistance rates above 10% are restricted to some US centers. Candida haemulonii complex isolates with poor susceptibility to azoles and amphotericin B have been isolated in superficial and deep-seated infections, whereas Candida guilliiermondii complex isolates with poor susceptibility to azoles and echinocandins have been recovered from catheter-related bloodstream infections. Other potential MDR Candida species are Candida krusei, Candida lusitaniae, Candida kefyr, Yarrowia (Candida) lypolitica, and Candida rugosa.


Electrophysiological evidence that neurokinin A acts via NK-1 receptors in the cat dorsal horn.
The aim of the present study was to investigate the effects of the non-peptide NK-2 receptor antagonist, SR 48968 on the responses of dorsal horn neurons to iontophoretic application of the endogenous NK-2 receptor ligand, neurokinin A, and on synaptically elicited responses in chloralose-anaesthetized cats. The effect of iontophoretic application of neurokinin A was tested on 51 dorsal horn neurons. Of these, 43 were wide dynamic range and the rest non-nociceptive neurons. Neurokinin A induced a slow, prolonged excitation of 25 of the wide dynamic range neurons. All remaining neurons were unaffected. SR 48968 (50 microg to 1.0 mg/kg, i.v.) did not affect the on-going basal activity (n = 8) or the slow excitation induced by neurokinin A in any of the nine wide dynamic range neurons tested. To eliminate the possibility that systemically administered SR 48968 may not be reaching central sites, SR 48968 was also applied iontophoretically (70-120 nA) to five neurons and tested against excitatory responses to iontophoretically applied neurokinin A. The on-going activity of these cells were unaffected by SR 48968. The responses to neurokinin A were also unaffected suggesting that neurokinin A did not mediate its effects via NK-2 receptors. SR 48968 also had no effect on the excitatory responses of seven neurons to iontophoretic application of the NK-1 receptor agonist, substance P indicating that substance P actions are not mediated via NK-2 receptors and that SR 48968 did not react with NK-1 receptors. Responses of the neurons to non-noxious (hair) stimulation (n = 10), noxious mechanical (n = 5) and noxious thermal (n = 8) stimulation of the receptive field were also unaffected by SR 48968, suggesting a lack of participation of NK-2 receptors in these responses. However, responses of wide dynamic range neurons to neurokinin A were totally blocked by i.v. administration (0.5 mg/kg) of the NK-1 receptor antagonists CP-96,345 (n = 7) and CP-99,994 (n = 5) but not by CP-96,344 (n = 4), the inactive enantiomer of CP-96,345. These data suggest that neurokinin A, like substance P may be acting via NK-1, rather than NK-2 receptors, to produce excitation of wide dynamic range neurons in the dorsal horn of the cat spinal cord.


Exploring Gender and Racial/Ethnic Differences in the Effects of Child Sexual Abuse.
Child sexual abuse (CSA) has been linked to a number of adverse effects including hypersexuality (HYP), substance use (SUB), suicidality (SUI), and depression (DEP). Despite a plethora of research on CSA, little is known about how it affects adolescents and the cultural factors that influence their coping styles. This study was founded on social-cultural coping theory and the model of traumagenic dynamics of sexual abuse, suggesting that CSA consequences lead to maladaptive coping mechanisms influenced by sociocultural factors. Using archival data, loglinear analysis was conducted to examine gender differences within racial/ethnic groups in HYP, SUI, DEP, and SUB among adolescent survivors of CSA in a National sample of 13,583 male and female high school students. The purpose of the study was to identify differences in the effects of CSA as manifested by variations of maladaptive coping across racial/ethnic groups and gender. Boys were significantly more likely to use substances, while girls were more likely to experience depressive symptoms and suicidality. Notably, this study did not reveal any significant racial/ethnic differences in adolescent coping. These findings can inform treatment planning and interventions for adolescents who may present with DEP, SUI, SUB, or risky sexual behaviors, but may have underlying trauma from CSA. This study contributes to the knowledge base about the processes that take place within adolescent CSA survivors, shedding light on cultural nuances among adolescent coping and informing culturally competent practice.


Sevoflurane pretreatment enhance HIF-2α expression in mice after renal ischemia/reperfusion injury.
Ischemia/reperfusion (I/R) injury often occurs, which is one of the major causes of acute kidney injury, thus increasing in-hospital mortality. HIF-2α has a protective role against ischemia of the kidney. Renal ischemia/reperfusion under sevoflurane anesthesia resulted in drastic improvements in renal function. We hypothesized that underlying mechanism responsible for renal protection from sevoflurane pretreatment involves the upregulation of HIF-2α. Sevoflurane pretreatment were performed on WT and HIF-2α knockout mice before renal ischemia/reperfusion. Levels of blood urea nitrogen (BUN) and serum creatinine (Cr) were determined with a standard clinical automatic analyzer. The left kidneys were taken for morphological examination. Expression of HIF-2α in kidney tissue was examined by western blotting. In WT mice, group I/R injury had significantly higher BUN and Cr levels than group control, whereas group I/R + Sev had significantly lower BUN and Cr levels than group I/R injury. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. In HIF-2α(-/-) mice, group I/R + Sev showed much higher BUN and Cr levels and severer histological damage than group I/R and group control. Renal HIF-2α expression levels were significantly higher in WT mice of group I/R + Sev than group control and group I/R. Our findings suggested that HIF-2α might contribute to the beneficial effect of sevoflurane in renal ischemia/reperfusion injury.


Late management of cleft lip and palate problems: a joint orthodontic/surgical approach.
Three patients are presented from a larger case series of adolescent cleft lip and palate patients to illustrate a combined approach to the treatment of severe facial and dentoalveolar discrepancy. The following treatment regime was employed: orthopaedic expansion of the maxillary dentoalveolus; tertiary bone grafting of the alveolar cleft; upper and lower dental arch alignment and decompensation; and orthognathic surgery to correct the skeletal defect by means of a maxillary single unit advancement. The advantages of tertiary grafting (when secondary grafting has not been carried out) in the orthodontic and surgical management of these patients is discussed.


Physical activity and risk of hypertension: a meta-analysis of prospective cohort studies.
Published literature reports controversial results about the association of physical activity (PA) with risk of hypertension. A meta-analysis of prospective cohort studies was performed to investigate the effect of PA on hypertension risk. PubMed and Embase databases were searched to identify all related prospective cohort studies. The Q test and I(2) statistic were used to examine between-study heterogeneity. Fixed or random effects models were selected based on study heterogeneity. A funnel plot and modified Egger linear regression test were used to estimate publication bias. Thirteen prospective cohort studies were identified, including 136,846 persons who were initially free of hypertension, and 15,607 persons developed hypertension during follow-up. The pooled relative risk (RR) of main results from these studies suggests that both high and moderate levels of recreational PA were associated with decreased risk of hypertension (high versus low: RR, 0.81; 95% confidence interval, 0.76-0.85 and moderate versus low: RR, 0.89; 95% confidence interval, 0.85-0.94). The association of high or moderate occupational PA with decreased hypertension risk was not significant (high versus low: RR, 0.93; 95% confidence interval, 0.81-1.08 and moderate versus low: RR, 0.96; 95% confidence interval, 0.87-1.06). No publication bias was observed. The results of this meta-analysis suggested that there was an inverse dose-response association between levels of recreational PA and risk of hypertension, whereas there was no significant association between occupational PA and hypertension.


First adaptation of coping power program as a classroom-based prevention intervention on aggressive behaviors among elementary school children.
Children with high levels of aggressive behavior create a major management problem in school settings and interfere with the learning environment of their classmates. We report results from a group-randomized trial of a program aimed at preventing aggressive behaviors. The purpose of the current study, therefore, was to determine the extent to which an indicated prevention program, Coping Power Program, is capable of reducing behavioral problems and improving pro-social behavior when delivered as a universal classroom-based prevention intervention. Nine classes (five first grade and four second grade) were randomly assigned to intervention or control conditions. Findings showed a significant reduction in overall problematic behaviors and in inattention-hyperactivity problems for the intervention classes compared to the control classes. Students who received Coping Power Program intervention also showed more pro-social behaviors at postintervention. The implications of these findings for the implementation of strategies aimed at preventing aggressive behavior in school settings are discussed.


Revealing the structural origin of the redox-Bohr effect: the first solution structure of a cytochrome from Geobacter sulfurreducens.
Gs (Geobacter sulfurreducens) can transfer electrons to the exterior of its cells, a property that makes it a preferential candidate for the development of biotechnological applications. Its genome encodes over 100 cytochromes and, despite their abundance and key functional roles, to date there is no structural information for these proteins in solution. The trihaem cytochrome PpcA might have a crucial role in the conversion of electronic energy into protonmotive force, a fundamental step for ATP synthesis in the presence of extracellular electron acceptors. In the present study, 15N-labelled PpcA was produced and NMR spectroscopy was used to determine its solution structure in the fully reduced state, its backbone dynamics and the pH-dependent conformational changes. The structure obtained is well defined, with an average pairwise rmsd (root mean square deviation) of 0.25 Å (1 Å=0.1 nm) for the backbone atoms and 0.99 Å for all heavy atoms, and constitutes the first solution structure of a Gs cytochrome. The redox-Bohr centre responsible for controlling the electron/proton transfer was identified, as well as the putative interacting regions between PpcA and its redox partners. The solution structure of PpcA will constitute the foundation for studies aimed at mapping out in detail these interacting regions.


X-ray phase tomography of a moving object.
We propose an algorithm for tomographic reconstruction of the refractive index map of an object translated across a fan-shaped X-ray beam. We adopt a forward image model valid under the non-paraxial condition, and use a unique mapping of the acquired projection images to reduce the computational cost. Even though the imaging setup affords only a limited angular coverage, our algorithm provides accurate refractive index values by employing the positivity and piecewise-smoothness constraints.


Outside-in or Inside-out? A Randomized Controlled Trial of Two Empowerment Approaches for Family Caregivers of People with Schizophrenia.
Training-based intervention such as psychoeducational groups has become increasingly popular to empower family caregivers of people with schizophrenia, yet existing supportive programs for caregivers tend to focus more on the needs of the patients rather than the development of the caregivers. This study aimed to compare the outcomes of a skill-based empowerment psychoeducational group and an inner-resource enhancing empowerment narrative therapy group for family caregivers of people with schizophrenia. We conducted a randomized controlled trial with a longitudinal design. The sample consisted of 132 family caregivers who were randomly assigned to eight sessions of the two groups (i.e. a narrative-based group, or a psychoeducational group), or a control group with delayed treatment. Psychometric scales were administrated throughout the project. Both the psychoeducational group and the narrative group showed significant improvements in family relationships, caregiving burden, and coping skills compared with the control group across the three time points (pretest, posttest, and 2-month follow-up). A statistically significant advancement in coping skills was found in the psychoeducational group. The narrative group outperformed the psychoeducational group and the control group in the enhancement of inner resources, perceived control, and level of hope. The findings call for the need of an integrative empowerment approach that both values the inner strength and unique experiences of the caregivers and at the same time provides them with necessary skills and knowledge in taking care of their family members with schizophrenia.


Relationship between the position of the mental foramen and the anterior loop of the inferior alveolar nerve as determined by cone beam computed tomography combined with mimics.
The position of the mental foramen and the anterior loop length of the inferior alveolar nerve serve as important anatomical landmarks for surgical procedures in the anterior mandibular region. The purpose of this study was to determine the relationship between the anterior loop of the inferior alveolar nerve and the mental foramen by combining cone beam computed tomography and Mimics, a software used to construct 3-dimensional (3D) interactive models of anatomical structures. Cone beam computed tomography images from a total of 60 patients were obtained and studied using GALAXY viewer or were imported into Mimics. The anterior loop of the inferior alveolar nerve was reconstructed 3-dimensionally, and then relevant parameters were measured. The parameters were measured, and their values include mean (SD) anterior loop length, 1.16 (1.78) mm; anterior loop angle, 19.13 (26.89) degrees; inferior alveolar canal diameter, 3.01 (0.67) mm; height of the inferior alveolar canal, 10.32 (1.56) mm; 2-dimensional mental foramen diameter, 2.97 (0.61) mm; 3D mental foramen diameter, 2.95 (0.59) mm; 2-dimensional vertical height of the mental foramen, 14.67 (1.67) mm; and 3D vertical height of the mental foramen, 14.61 (1.69) mm. The mental foramen was located apically between the first and second premolars in 51.67% and below the second premolar in 40.83% of the cases. A relationship was observed between the location of the mental foramen and the presence of the anterior loop of the inferior alveolar nerve. We highlight the effectiveness of cone beam computed tomography and 3D reconstruction in the identification of important anatomical structures relevant for preoperative assessment for surgical procedures in the anterior region of the mandible.


Strategies for incorporating patient-reported outcomes in the care of people with chronic kidney disease (PRO kidney): a protocol for a realist synthesis.
Patient-reported outcomes and experience measures (jointly referred to here as PROs) are internationally recognized as a means for patients to provide information about their quality of life, symptoms, and experiences with care. Although increasingly recognized as key to improving the quality of healthcare at individual (e.g., patients, caregivers, and providers) and aggregate (e.g., government, policy/system-wide decision-making) levels, there are important knowledge gaps in our understanding of how PROs are, and can be, used across different settings, particularly in nephrology to enhance person-centered care. This knowledge is needed for developing strategies to guide optimal use of PROs in nephrology care. Currently, no strategies exist. The purpose of this review is to address this knowledge gap by answering the following realist question: How can PROs be used to enhance person-centered nephrology care, both at individual and aggregate levels? Realist synthesis is an explanatory approach to data synthesis that aims to explain how context and mechanisms influence the outcome of an intervention. An initial program theory will be developed through the systematic search of the published literature in bibliographic databases (Ovid MEDLINE, Ovid Embase, EBSCOhost CINAHL, Web of Science, and Scopus) on existing theories explaining how PROs are used in healthcare settings. This initial program theory will then be tested and refined through the process of realist synthesis, using context-mechanism-outcome configurations. A kidney-specific program theory will then be created to address the utilization of PROs in nephrology across individual and aggregate levels to augment person-centered care. Searching will be iterative and refined as data is extracted and analyzed using a pilot-tested context + mechanism = outcome heuristic. Throughout, we will consult methodological experts, research team practitioners, and the Patient Advisory Committee to help refine the theories. Last, we will develop and disseminate knowledge translation products widely to knowledge user groups. The utilization of PROs remains a challenge in nephrology. The findings from this synthesis will provide a framework to guide both policy makers and practitioners on how to enhance person-centered care through successful utilization of PROs across individual and aggregate levels in nephrology. PROSPERO CRD42017056063.


From local pixel structure to global image super-resolution: a new face hallucination framework.
We have developed a new face hallucination framework termed from local pixel structure to global image super-resolution (LPS-GIS). Based on the assumption that two similar face images should have similar local pixel structures, the new framework first uses the input low-resolution (LR) face image to search a face database for similar example high-resolution (HR) faces in order to learn the local pixel structures for the target HR face. It then uses the input LR face and the learned pixel structures as priors to estimate the target HR face. We present a three-step implementation procedure for the framework. Step 1 searches the database for K example faces that are the most similar to the input, and then warps the K example images to the input using optical flow. Step 2 uses the warped HR version of the K example faces to learn the local pixel structures for the target HR face. An effective method for learning local pixel structures from an individual face, and an adaptive procedure for fusing the local pixel structures of different example faces to reduce the influence of warping errors, have been developed. Step 3 estimates the target HR face by solving a constrained optimization problem by means of an iterative procedure. Experimental results show that our new method can provide good performances for face hallucination, both in terms of reconstruction error and visual quality; and that it is competitive with existing state-of-the-art methods.


A retrospective study of red cell maternal antibodies by chemiluminescence.
Plasma samples from 109 patients with maternal IgG alloantibodies were investigated using a chemiluminescence (CL) assay, a functional test, to predict which antibodies were clinically significant. The CL assay was able to distinguish between those patients who were unaffected or mildly affected requiring only phototherapy, and those patients with moderate or severe haemolytic disease of the fetus or newborn (HDN) requiring transfusion therapy. The CL result was compared with the anti-D quantification result, the number of IgG molecules bound per red cell and, in 80% of the cases, the monocyte monolayer assay. If mothers carrying Rh-negative fetuses were ignored, then the CL assay correctly predicted the outcome for 93.4% of all cases (including those other than D), while the AutoAnalyzer and monocyte assay predicted correctly 92.7% (of the anti-D patients) and 81.5%, respectively. Greater than 80% of patients with severe or moderate HDN had both IgG1 + IgG3 subclasses in the maternal plasma, while those infants who were unaffected or only mildly affected had a greater chance of having IgG1 only (44%) in the maternal plasma, IgG3 only (27%) or both subclasses (29%).


Changes in the organizational structure of public health nurse service in the Republic of Croatia 1995 to 2012.
Since 1996, after the privatization of primary health care, public health nurse (PHN) in Croatia remained employed within the health center, mainly responsible for the preventive care of the inhabitants from defined catchment's area. Before that time they were part of general practice teams. The main aim of the study was to investigate what are the trends in the organizational structure of PHN service in Croatia, from 1995-2012. The main source was the Croatian Health Service Yearbooks. The obtained results shows that they are college educated and mostly in full-time jobs. The important findings are the lack of nurses and theirs regional differences. In highly demanding societies, with growing numbers of elderly, mental, social and economic problems, it will be worthy to consider the lower standard then 5 100 inhabitants per one PHN. Also, it should be taken into account to invest into the lowering of regional disparities.


Identification of a minus end-specific microtubule-associated protein located at the mitotic poles in cultured mammalian cells.
A mitosis-specific centrosomal component was studied with a human autoantibody, SP-H, which immunostained mitotic poles and interphase nuclei, and a single polypeptide with an apparent molecular mass of 200 to 230 kDa in various lines of cultured cells. Early mitotic PtK1 cells treated with 10 micrograms/ml taxol contained short bundles of parallel microtubules around the nuclei and cell periphery. At the time of nuclear envelope breakdown, the nuclear staining by SP-H disappeared, and the antigen relocated at one end of the parallel microtubules. Determination of the microtubule polarity demonstrated that the peripheral bundles of microtubules were arranged with their minus ends directed to the cell periphery, and the SP-H antigen was specifically localized at this end. Parallel microtubules were further rearranged first into a fan-like shape, and then into completely radial structures as observed by De Brabander et al. (Int. Rev. Cytol. 101, 215-274 (1986)). The SP-H antigen was always detected at the minus end domain of such microtubule-containing structures during the transformation process. When microtubules were depolymerized by nocodazole treatment, the SP-H antigen appeared as discrete cytoplasmic foci, suggesting that the antigen may self-associate, forming multimeric structures. The antigen in mitotic HeLa cell extracts co-sedimented in vitro with exogenous brain microtubules. The microtubule-associated SP-H antigen was insensitive to ATP extraction, but was removed from microtubules by treatment with 0.5 M NaCl. Thus the 200 to 230 kDa centrosomal component could be a novel microtubule-associated protein with affinity for the minus end of microtubules, and it might play an essential role in the organization of spindle poles during mitosis.


Medical therapy as the primary modality for the management of chronic rhinosinusitis.
Chronic rhinosinusitis (CRS) is a prevalent disease with many potential interventions including medical and surgical treatments. Because CRS is a chronic condition it is essential that therapy limits exacerbations. The purpose of this article is to show that literature supports the implementation of aggressive medical management as the mainstay of therapy for CRS. Scientific literature on the use of intranasal and systemic corticosteroids, antibiotics, nasal saline lavages, and unique therapies for individuals with CRS (both with and without nasal polyps) are reviewed. In addition, literature comparing outcomes of medical therapy versus surgical therapy are reviewed. There is ample evidence of the beneficial effects of intranasal corticosteroids (INCSs) in CRS. The literature also favors the use of systemic corticosteroids in acute exacerbations of disease in patients with nasal polyps. Although antibiotics are commonly used for acute sinusitis, there is also evidence of their potential value in CRS. The literature indicates that saline lavages show benefit in the treatment of CRS. In addition, there are promising new biological therapies on the horizon with mepoluzimab and omalizumab. At least one study comparing medical therapy versus surgical therapy for CRS found no advantage for either modality. Treatment of CRS with aggressive medical management can potentially postpone the need for surgical intervention. Clinicians should use INCSs and nasal saline lavages as maintenance therapy. Systemic corticosteroids and antibiotics should be used for acute exacerbations, especially in individuals with nasal polyps.


The origins of cyanobactin chemistry and biology.
The correct structure of the symmetrical cyanobactin, ascidiacyclamide, was published in Chemical Communications by Hamamoto et al. in 1983. The cyanobactin family of compounds are cyclic peptides with modifications including azole/azoline rings, D-stereocentres and in some cases prenyl groups. Although related compounds were isolated earlier by Ireland et al., two of the three published structures later had to be corrected. Hamamoto's ascidiacyclamide structure assisted the understanding of the chemistry, bioactivity, biological origin and biosynthesis of this group of compounds. Cyanobactins are of interest as new chemotypes for the treatment of a range of diseases, in particular those in which extended binding sites are implicated.


Peripheral blood leucocytes show differential expression of tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection: a prospective matched cohort study.
Anastomotic leak is associated with higher rates of recurrence after surgery for colorectal cancer. However, the mechanisms responsible are unknown. We hypothesized that the infection-induced inflammatory response may induce overexpression of tumour progression-related genes in immune cells. The aim was to investigate the effect of postoperative intra-abdominal infection on the gene expression patterns of peripheral blood leucocytes (PBL) after surgery for colorectal cancer. Prospective matched cohort study. Patients undergoing surgery for colorectal cancer were included. Patients who had anastomotic leak or intra-abdominal abscess were included in the infection group (n = 23) and matched with patients without complications for the control group (n = 23). PBL were isolated from postoperative blood samples. Total RNA was extracted and hybridized to the Affymetrix Human Gene 1.0 ST microarray. Patients in the infection group displayed 162 upregulated genes and 146 downregulated genes with respect to the control group. Upregulated genes included examples coding for secreted cytokines involved in tumour growth and invasion (S100P, HGF, MMP8, MMP9, PDGFC, IL1R2). Infection also upregulated some proangiogenic genes (CEP55, TRPS1) and downregulated some inhibitors of angiogenesis (MME, ALOX15, CXCL10). Finally, some inhibitors (HP, ORM1, OLFM4, IRAK3) and activators (GNLY, PRF1, FGFBP2) of antitumour immunity were upregulated and downregulated, respectively, suggesting that the inflammatory environment caused by a postoperative infection favours immune evasion mechanisms of the tumour. Analysis of PBL shows differential expression of certain tumour progression-related genes in colorectal cancer patients who have a postoperative intra-abdominal infection, which in turn may promote the growth of residual cancer cells to become recurrent tumours.


Challenging Stereotypes: A Counter-Narrative of the Contraceptive Experiences of Low-Income Latinas.
Purpose: Reproductive autonomy is associated with educational attainment, advanced employment, and well-being. While U.S. Latinas use contraception to control their own childbearing and have reported a desire to do so, they often use it inconsistently and have the lowest rates of contraceptive use of any group. Reasons previously cited for why Latinas do not use contraception compared with non-Latino white women include lack of access, lack of knowledge, language barriers, emphasis on large families, machismo, and religiosity. These reasons are often overly simplistic and can lead to widespread generalizations about Latinas. Methods: Using focus groups and semistructured interviews from November 2014 through June 2015, this study describes the family planning perspectives and experiences of 16 Latinas living in Baltimore and recruited from two federally qualified health centers. A social determinant of health framework was used to guide identification of important concepts and explain findings. Results: Results demonstrated that respondents reported contraceptive agency and claimed autonomy over their bodies; described a sense of responsibility and often expressed caution about having families too large to care for; expressed educational and career aspirations; and perceived contraception as critical for the postponement of childbearing to achieve their goals. Conclusion: The patient/provider encounter should include communication that recognizes all patient preferences and lived experiences to support vulnerable and/or marginalized Latinas in their desires to control their own childbearing and life choices.


The relationship of current depressive symptoms and past depression with cognitive impairment and instrumental activities of daily living in an elderly population: the Sydney Memory and Ageing Study.
Depressive symptoms are common in the elderly and they have been associated with cognitive and functional impairment. However, relatively less is known about the relationship of a lifetime history of depression to cognitive impairment and functional status. The aim of this cross-sectional study was to assess whether current depressive symptoms and past depression are associated with cognitive or functional impairment in a community-based sample representative of east Sydney, Australia. We also examined whether there was an interaction between current and past depression in their effects on cognitive performance. Eight hundred non-demented aged participants received a neuropsychological assessment, a past psychiatric history interview and the 15-item Geriatric Depression Scale. The Bayer-Activities of Daily Living scale was completed by an informant to determine functional ability. Clinically relevant depressive symptoms were present in 6.1% of the sample and 16.6% reported a history of depression. Participants with current depression had significantly higher levels of psychological distress and anxiety, and lower life satisfaction and performed worse on memory and executive function compared to participants without current depression. After controlling for anxiety the effect on executive function was no longer significant while the effect on memory remained significant. A history of depression was associated with worse executive function, higher levels of psychological distress and anxiety, and lower life satisfaction. After controlling for psychological distress the effect of past depression on executive function was no longer significant. There were no significant interactions between current and past depression in their effects on cognitive performance. There were no differences between participants with or without current depression and with or without past depression on functional abilities. These results support the view that current and past depressive episodes are associated with poorer cognitive performance but not with functional abilities.


Phenotypic and Molecular Detection of Biofilm Formation in Staphylococcus aureus Isolated from Different Sources in Algeria.
Staphylococcus aureus is an opportunistic bacterium causing a wide variety of diseases. Biofilm formation of Staphylococcus aureus is of primary public and animal health concern. The purposes of the present study were to investigate the ability of Staphylococcus aureus isolated from animals, humans, and food samples to form biofilms and to screen for the presence of biofilm-associated and regulatory genes. In total, 55 Staphylococcus aureus isolated from sheep mastitis cases (n = 28), humans (n = 19), and from food matrices (n = 8) were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). The ability of Staphylococcus aureus for slime production and biofilm formation was determined quantitatively. A DNA microarray examination was performed to detect adhesion genes (icaACD and biofilm-associated protein gene (bap)), genes encoding microbial surface components recognizing adhesive matrix molecules (MSCRAMMs), regulatory genes (accessory gene regulator (agr) and staphylococcal accessory regulator (sarA)), and the staphylococcal cassette chromosome mec elements (SCCmec). Out of 55 Staphylococcus aureus isolates, 39 (71.0%) and 23 (41.8%) were producing slime and biofilm, respectively. All Staphylococcus aureus strains isolated from food showed biofilm formation ability. 52.6% of the Staphylococcus aureus strains isolated from sheep with mastitis, and 17.9% of isolates from humans, were able to form a biofilm. Microarray analysis typed the Staphylococcus aureus into 15 clonal complexes. Among all Staphylococcus aureus isolates, four of the human isolates (21.1%) harbored the mecA gene (SCCmec type IV) typed into 2 clonal complexes (CC22-MRSA-IV and CC80-MRSA-IV) and were considered as methicillin-resistant, while two of them were slime-producing. None of the isolates from sheep with mastitis harbored the cna gene which is associated with biofilm production. The fnbB gene was found in 100%, 60% and 40% of biofilm-producing Staphylococcus aureus isolated from food, humans, and sheep with mastitis, respectively. Three agr groups were present and agr group III was predominant with 43.6%, followed by agr group I (38.2%), and agr group II (18.2%). This study revealed the capacity of Staphylococcus aureus isolates to form biofilms and highlighted the genetic background displayed by Staphylococcus aureus isolates from different sources in Algeria.


A dual-channel signal averager for spontaneous signals.
This signal averager has been developed for spontaneous transients of tension and of aequorin bioluminescence in skinned cardiac cells. The signal with the largest signal-to-noise ratio (generally the tension transient) is entered in Channel 1 and triggers the system. Then the averager will unmask the signal entered in Channel 2 if it was buried in the noise during the direct recording. This signal averager uses an inexpensive microcomputer and a program written in Assembly Language. To facilitate its use, the averager is remotely controlled by a potentiometer for the adjustment of the threshold voltage above which the signal in Channel 1 will be collected and by three push buttons for starting the data collection, for averaging and displaying the results, and for resetting the system. The display is purely analog on the recorder, including averaged signals and interval for the signals in both channels together with a graphical representation of the standard deviations and of the number of observations. This signal averager could be used for any preparations developing spontaneous signals with variable intervals, provided that at least one of the synchronous signals has a large enough signal-to-noise ratio to trigger the system.


Neopterin as a biomarker of immune response in cancer patients.
With the advent of immunotherapy the topic of biomarkers of immune response is of high interest. Along with the expression of programmed death ligand 1 (PD-L1) or tumor infiltrating lymphocytes (TIL), biomarkers of macrophage activation could be of interest. Neopterin is a biomarker of immune activation increased in different disorders associated with immune activation, including cancer. Neopterin synthesis is induced by interferon-γ that also induces indoleamine 2,3-dioxygenase (IDO), an enzyme catalyzing catabolism of tryptophan to kynurenine. Increased urinary or serum concentrations of neopterin have been associated with poor prognosis across a spectrum of malignant disorders of different primary location. Neopterin concentration in peripheral blood as well as in the tumor microenvironment correlates with phenotypic and functional changes of lymphocytes, indicating immune dysfunction. Increased neopterin concentrations are also accompanied by increased rate of conversion of tryptophan to kynurenine. Increasing neopterin concentrations also accompany side effects of anticancer treatment and could predict subsequent complications. Although almost four decades have elapsed since the discovery of increased neopterin concentrations in cancer patients, the full potential of neopterin as a biomarker in this setting has not been so far realized.


Aortic pressure augmentation as a marker of cardiovascular risk in obstructive sleep apnea syndrome.
Obstructive sleep apnea syndrome (OSAS) is associated with increases in cardiovascular morbidity and mortality. Vascular changes in individuals with OSAS have not been fully elucidated, however. The possible impact of OSAS on the extent of aortic pressure augmentation (AG), an indicator of cardiovascular risk, was investigated. Forty-five consecutive male patients aged 35 to 78 years (56.0+/-9.6 years) who were referred to the sleep clinic of Nagoya University Hospital for screening and treatment of OSAS and 71 age-matched healthy men were enrolled in the study. AG was derived from the pressure waveform measured at the radial artery by applanation tonometry. The number of apnea and hypopnea episodes per hour (apnea-hypopnea index [AHI]) was determined by standard polysomnography. AG was significantly greater in OSAS patients than in controls (9.0+/-4.1 vs. 6.4+/-3.4 mmHg, p<0.001), and it was significantly reduced in 19 OSAS patients treated with continuous positive airway pressure. AG was also significantly correlated with the AHI (r=0.562, p<0.001) and age (r=0.356, p=0.016) but not with the serum concentrations of low and high density lipoprotein-cholesterol, triglyceride, or glycosylated hemoglobin. Stepwise multiple regression analysis revealed that the AHI was the most significant contributing factor to the increased AG in OSAS patients (beta=0.109, r=0.530, p<0.001). OSAS may thus have an adverse effect on vascular function that can be ameliorated by appropriate treatment.


Prevention of groin injuries in sports: a systematic review with meta-analysis of randomised controlled trials.
Groin injuries are common in football and ice hockey, and previous groin injury is a strong risk factor for future groin injuries, which calls for primary prevention. The aim of this systematic review was to evaluate the effect of specific groin-injury prevention programmes in sports. A comprehensive search was performed in May 2014 yielding 1747 potentially relevant references. Two independent assessors evaluated randomised controlled trials for inclusion, extracted data and performed quality assessments using Cochrane's risk of bias tool. Quantitative analyses were performed in Review Manager 5.3. Seven trials were included: six on football players (four male and two female populations) and one on male handball players. In total there were 4191 participants with a total of 157 injuries. The primary analysis, including all participants, did not show a significant reduction in the number of groin injuries after completing a groin injury prevention programme (relative risk (RR) 0.81; 95% CI 0.60 to 1.09). Subgroup analysis based on type of sports, gender and type of prevention programme showed similar non-significant estimates with RR ranging from 0.48 to 0.81. Meta-analysis revealed a potential clinically meaningful groin injury reduction of 19%, even though no statistical significant reduction in sport-related groin injuries could be documented. PROSPERO registration ID CRD42014009614.


Role of the acceptor in tuning the properties of metal [M(II) = Ni, Pd, Pt] dithiolato/dithione (donor/acceptor) second-order nonlinear chromophores: combined experimental and theoretical studies.
The mixed-ligand complexes [M(II)(Et2dazdt)(mnt)] (M = Ni, 1; Pd, 2; Pt, 3) [Et2dazdt = N,N'-diethyl-perhydrodiazepine-2,3-dithione; mnt = maleonitrile-2,3-dithiolate] have been prepared and fully characterized. X-ray diffractometric studies on 1-3 (the structure of 1 was already known) show that the crystals are isostructural (triclinic, P-1), and two independent molecular entities are present in the unit cell. These entities differ in the orientation of the ethyl substituents with respect to the epta-atomic ring. In the C2S2MS2C2 dithiolene core the four sulfur atoms define a square-planar coordination environment of the metal where the M-S bond distances involving the two ligands are similar, while the C-S bond distances in the C2S2 units exhibit a significant difference in Et2dazdt (dithione) and mnt (dithiolato) ligands. 1-3 show in the visible region one or two moderately strong absorption peaks, having ligand-to-ligand charge-transfer (CT) character with some contribution of the metal, and show negative solvatochromism and molecular quadratic optical nonlinearity, which was determined by the EFISH (electric-field-induced second-harmonic generation) technique. These complexes are redox active and show two reversible reduction waves and one irreversible oxidation wave. Theoretical calculations based on DFT and TD-DFT calculations on complexes 1-3 as well as on [Pt(Bz2pipdt)(mnt)] (4) and [Pt(Bz2pipdt)(dmit)] (5) highlight the factors which affect the optical properties of these second-order redox-active NLO chromophores. Actually, the torsion angle of the dithione system (δ2) inversely correlates either with the oscillator strengths of the main transition of the complexes or with their beta values. The high beta value of 5 can be attributed both to its lowest torsion angles and to the extent of the π system of its dithiolate ligand, dmit.


Which source should we use to measure quality of life in children with asthma: the children themselves or their parents?
This study compares the reproducibility, construct validity and responsiveness of self-report and parent-report quality of life questionnaires How Are You (HAY) for 8-12-year-old children with asthma. A total of 228 Dutch children with asthma and their parents completed the HAY and daily recorded the child's asthma symptoms in a diary. Additionally 296 age- and -gender matched healthy children and their parents completed the generic part of the HAY. Reproducibility and responsiveness were examined in a sub-group of 80 children with asthma. In this group, three measurements were carried out, at baseline, after one week and once during the following 6 month when the clinical asthma status had changed. The within-subject standard deviations (SD) of three dimensions (physical activities, social activities, self-management) differed significantly (p < 0.05) in favour of the parent-version, indicating that the reproducibility of the parent version was better than that of the child version. The mean score-differences between children with asthma and healthy children as reported by parents did not significantly differ from those reported by children, except for cognitive activities (e.g. be able to concentrate on school work). The mean differences with regard to children with a different actual asthma status (symptom analysis), as reported by both informants, did not differ. Compared to the child-version, the parent-version showed greater ability to detect changes in children's quality of life over time for all but one dimension, indicating better responsiveness. The results indicate that in discriminative studies child and parents reports can be substituted on a group-level. In longitudinal studies data have to be obtained from parents. Consequently, caregivers collecting quality of life data for longitudinal purposes in daily practice should collect these data simply from parents.


Permeability Parameters Measured with Dynamic Contrast-Enhanced MRI: Correlation with the Extravasation of Evans Blue in a Rat Model of Transient Cerebral Ischemia.
The purpose of this study was to correlate permeability parameters measured with dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) using a clinical 3-tesla scanner with extravasation of Evans blue in a rat model with transient cerebral ischemia. Sprague-Dawley rats (n = 13) with transient middle cerebral artery occlusion were imaged using a 3-tesla MRI with an 8-channel wrist coil. DCE-MRI was performed 12 hours, 18 hours, and 36 hours after reperfusion. Permeability parameters (K(trans), ve, and vp) from DCE-MRI were calculated. Evans blue was injected after DCE-MRI and extravasation of Evans blue was correlated as a reference with the integrity of the blood-brain barrier. Correlation analysis was performed between permeability parameters and the extravasation of Evans blue. All permeability parameters (K(trans), ve, and vp) showed a linear correlation with extravasation of Evans blue. Among them, K(trans) showed highest values of both the correlation coefficient and the coefficient of determination (0.687 and 0.473 respectively, p < 0.001). Permeability parameters obtained by DCE-MRI at 3-T are well-correlated with Evans blue extravasation, and K(trans) shows the strongest correlation among the tested parameters.


In situ plasmonic counter for polymerization of chains of gold nanorods in solution.
Self-assembly of gold nanorods (NRs) in linear, polymer-like chains offers the ability to test and validate theoretical models of molecular polymerization. Practically, NR chains show multiple promising applications in sensing of chemical and biological species. Both areas of research can strongly benefit from the development of a quantitative tool for characterization of the structure of NR chains in the course of self-assembly, based on the change in ensemble-averaged optical properties of plasmonic polymers; however, quantitative correlation between the extinction spectra and the structural characteristics of NR chains has not been reported. Here, we report such a tool by a quantitatively correlating the red shift of the longitudinal surface plasmon band of gold NRs and the average aggregation number of NR chains. The generality of the method is demonstrated for NRs with different aspect ratios, for varying inter-rod distances in the chains, and for varying initial concentrations of NRs in solution. We modeled the extinction spectra of the NR chains by combining the theory of step-growth polymerization with finite-difference time-domain simulations and a resistor-inductor-capacitor model, and obtained agreement between the theoretical and experimental results. In addition to capturing quantitatively the ensemble physics of the polymerization, the proposed 'plasmonic counter' approach provides a real-time cost- and labor-efficient method for the characterization of self-assembly of plasmonic polymers.


In situ synthesis of silver nanowire gel and its super-elastic composite foams.
Noble-metal aerogels (NMAs) including silver aerogels have drawn increasing attention because of their highly conductive networks, large surface areas, and abundant optically/catalytically active sites. However, the current approaches of fabricating silver aerogels are tedious and time-consuming. In this regard, it is highly desirable to develop a simple and effective method for preparing silver aerogels. Herein, we report a facile strategy to fabricate silver gels via the in situ synthesis of silver nanowires (AgNWs). The obtained AgNW aerogels show superior electrical conductivity, ultralow density, and good mechanical robustness. AgNW aerogels with a density of 24.3 mg cm-3 display a conductivity of 2.1 × 105 S m-1 and a Young's modulus of 38.7 kPa. Furthermore, using an infiltration-air-drying-crosslinking technique, polydimethylsiloxane (PDMS) was introduced into 3 dimensional (3D) AgNW networks for preparing silver aerogel/elastomer composite materials. The obtained AgNW/PDMS aerogel composite exhibits outstanding elasticity while retaining excellent electrical conductivity. The fast piezoresistive response proves that the aerogel composite has a potential application for vibration sensors.


Reversible electrical reduction and oxidation of graphene oxide.
We demonstrate that graphene oxide can be reversibly reduced and oxidized using electrical stimulus. Controlled reduction and oxidation in two-terminal devices containing multilayer graphene oxide films are shown to result in switching between partially reduced graphene oxide and graphene, a process which modifies the electronic and optical properties. High-resolution tunneling current and electrostatic force imaging reveal that graphene oxide islands are formed on multilayer graphene, turning graphene into a self-assembled heterostructure random nanomesh. Charge storage and resistive switching behavior is observed in two-terminal devices made of multilayer graphene oxide films, correlated with electrochromic effects. Tip-induced reduction and oxidation are also demonstrated. Results are discussed in terms of thermodynamics of oxidation and reduction reactions.


Halotolerant rhizobacteria Pseudomonas pseudoalcaligenes and Bacillus subtilis mediate systemic tolerance in hydroponically grown soybean (Glycine max L.) against salinity stress.
Salt stress is one of the devastating factors that hampers growth and productivity of soybean. Use of Pseudomonas pseudoalcaligenes to improve salt tolerance in soybean has not been thoroughly explored yet. Therefore, we observed the response of hydroponically grown soybean plants, inoculated with halotolerant P. pseudoalcaligenes (SRM-16) and Bacillus subtilis (SRM-3) under salt stress. In vitro testing of 44 bacterial isolates revealed that four isolates showed high salt tolerance. Among them, B. subtilis and P. pseudoalcaligenes showed ACC deaminase activity, siderophore and indole acetic acid (IAA) production and were selected for the current study. We determined that 106 cells/mL of B. subtilis and P. pseudoalcaligenes was sufficient to induce tolerance in soybean against salinity stress (100 mM NaCl) in hydroponics by enhancing plant biomass, relative water content and osmolytes. Upon exposure of salinity stress, P. pseudoalcaligenes inoculated soybean plants showed tolerance by the increased activities of defense related system such as ion transport, antioxidant enzymes, proline and MDA content in shoots and roots. The Na+ concentration in the soybean plants was increased in the salt stress; while, bacterial priming significantly reduced the Na+ concentration in the salt stressed soybean plants. However, the antagonistic results were observed for K+ concentration. Additionally, soybean primed with P. pseudoalcaligenes and exposed to 100 mM NaCl showed a new protein band of 28 kDa suggesting that P. pseudoalcaligenes effectively reduced salt stress. Our results showed that salinity tolerance was more pronounced in P. pseudoalcaligenes as compared to B. subtilis. However, a detailed study at molecular level to interpret the mechanism by which P. pseudoalcaligenes alleviates salt stress in soybean plants need to be explored.


Tackling STI epidemics through the HIV clinic: is sex high enough on the agenda?
Sexually transmitted infection (STI) rates among men having sex with men continue to increase. HIV services may operate independently to genitourinary medicine clinics and the sexual health of HIV-positive patients may be of low priority in the context of medical problems related to HIV. A prospective study of HIV-positive gay men was conducted in a London outpatient clinic over a three-month period. Data were available for 90 men. Forty-five percent had STI screens in the preceding six months. These revealed a high rate of infections; 26 infections diagnosed in 14 men in the study period. Fifty-seven percent of the 90 men in the study had more than one partner in the past three months and approximately one-third had unprotected sexual activity. A significant proportion of men were unaware of recent outbreaks of hepatitis C and lymphogranuloma venereum and of HIV postexposure prophylaxis. We therefore recommend that sexual history-taking, STI screens and health promotion should become a routine feature of HIV outpatient consultations in this group.


Comparing multifocal VEP and standard automated perimetry in high-risk ocular hypertension and early glaucoma.
To compare the diagnostic performance of multifocal visual evoked potential (mfVEP) and standard automated perimetry (SAP), in eyes with high-risk ocular hypertension or early glaucoma. Both eyes of 185 individuals with high-risk ocular hypertension or early glaucoma were evaluated. Subjects ranged in age from 37 to 87 (mean +/- SD: 61 +/- 11 years). Pattern-reversal mfVEPs were obtained by using VERIS (Electro-Diagnostic Imaging, San Mateo, CA) with a four-electrode array and were analyzed with custom software. SAP visual fields (SITA-standard; Carl Zeiss Meditec, Inc., Dublin, CA) were obtained within 22.3 +/- 27.0 days of the mfVEP. Stereo disc photographs and Heidelberg Retina Tomograph (HRT) images were obtained during one visit, which was within 24.8 +/- 50.4 days of the mfVEP and 33.1 +/- 62.9 days of the SAP visual field. Abnormalities on the mfVEP were defined by using a variety of cluster criteria: SAP with pattern standard deviation (PSD) P </= 0.05 or glaucoma hemifield test (GHT) outside normal limits, according to OHTS criteria (SAP-OHTS). In separate analyses cluster criteria were used to determine SAP abnormalities. Disc photographs were graded as either glaucomatous optic neuropathy (GON) or normal by two independent masked experts, and disagreements were adjudicated by a third masked expert. The overall Moorfields regression analysis (MRA) result from the HRT was used as a separate diagnostic classification. All eyes classified as "borderline" by the MRA were assigned to the normal category (i.e., "within normal limits"). Sensitivity for mfVEP or SAP was defined as the percentage of GON eyes that had an abnormality on the functional test. Specificity for mfVEP or SAP was defined as the percentage of eyes with normal optic disc structure that had normal functional test results. Disc photographs from 50% of eyes were graded GON. Both eyes were graded GON in 71 (38%) of the 185 subjects. Exactly half as many eyes were abnormal by HRT MRA. The average SAP mean deviation (MD) was +0.3 +/- 2.1 dB; average PSD was 2.3 +/- 1.9 dB. By OHTS criteria, 83 (22%) of the 370 eyes had an abnormal SAP. Depending on the cluster criterion used, the proportion of eyes with an abnormal SAP ranged from 8% to 26% and with an abnormal mfVEP, from 14% to 45%. A criterion with an estimated specificity in normal subjects of 91% resulted in 102 (28%) eyes with an abnormal mfVEP. For criteria with estimated specificities of 95% and 99%, respectively, 88 (24%) eyes and 52 (14%) eyes had an abnormal mfVEP. Agreement between SAP and mfVEP ranged from 75% to 81%. The sensitivity of SAP-OHTS to detect GON (using the disc photograph as diagnostic standard) was 29%, whereas specificity was 84%. Sensitivity of the mfVEP to detect GON, for cluster criteria with disc structure specificity between 84% and 87%, ranged from 28% to 32%. When the HRT MRA was used as the diagnostic standard, sensitivities of both functional tests to detect GON increased to 42%. The diagnostic performance of mfVEP was similar to that of SAP. However, the two modalities agreed in only approximately 80% of eyes, suggesting that they may detect slightly different functional deficits.


[Comparison of the cutaneous response to Dermatophagoides farinae from 2 separate laboratories].
We compared in 50 asthmatic children, the cutaneous response by skin prick test to Dermatophagoides farinae with antigens from two different laboratories (Freeman and Hollister). In order to evaluate the importance of the selection, conservation and standardization of the allergic extracts. 27/50 children had a similar response, in those cases (6) where Freeman was doubtful and Hollister positive the allergic etiology was confirmed by RAST and Challenge tests. In 5 cases, Freeman was negative and Hollister doubtful we only confirm allergic etiology in 1. When both were positive all of them were allergic. The antigen Dermatophagoides farinae from Freeman laboratory needs another diagnostic method, when the cutaneous response is doubtful or negative and the clinical feature is highly suggestive. We don't have to forget the importance of the controls positive and negative.


Gender Differences in Neurodegeneration, Neuroinflammation and Na+-Ca2+ Exchangers in the Female A53T Transgenic Mouse Model of Parkinson's Disease.
Twelve-month-old male mice expressing the human A53T variant of α-synuclein (A53T) develop dopamine neuron degeneration, neuroinflammation, and motor deficits, along with dysfunctions of the mitochondrial Na+-Ca2+ exchanger (NCX) isoforms 1 (NCX1) and 3 (NCX3) in the nigrostriatal system. Since gender is thought to play a role in the etiology of Parkinson's disease (PD), we characterized neurochemical and behavioral alterations in 12-month-old female A53T transgenic mice. We investigated the presence of dopaminergic degeneration, astrogliosis and microgliosis using immunohistochemistry for tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule-1 (IBA-1) in both the substantia nigra pars compacta (SNc) and striatum. In the same regions, we also evaluated the co-localization of NCX1 in cells positive for IBA-1 and the co-localization of NCX3 in TH-positive neurons and fibers. Furthermore, in both male and female mice, we performed motor (beam walking and pole tests) and memory [novel object recognition (NOR) and spontaneous alternation] tasks, together with tests to evaluate peripheral deficits (olfactory and stool collection tests). Female A53T transgenic mice displayed degeneration of nigral dopaminergic neurons, but neither microgliosis nor astrogliosis in the SNc and striatum. Moreover, female A53T transgenic mice displayed co-localization between NCX1 and IBA-1 positive cells in the striatum but not SNc, whereas NCX3 did not co-localize with either TH-positive terminals or neuronal bodies in the nigrostriatal system. Furthermore, female A53T transgenic mice showed increased crossing time in the beam walking test, but no impairments in the pole or memory tests, and in tests that evaluated peripheral deficits, whereas male A53T transgenic mice displayed motor, memory and peripheral deficits. Immunohistochemical and behavioral results obtained here in the female mice differ from those previously observed in males, and suggest a dissimilar influence of NCX1 and NCX3 on dopaminergic function in female and male A53T transgenic mice, strengthening the validity of these mice as a model for studying the etiological factors of PD.


Identification of genes associated with fatty acid biosynthesis based on 214 safflower core germplasm.
Safflower (Carthamus tinctorius L.) is an oilseed crop with substantial medicinal and economic value. However, the methods for constructing safflower core germplasm resources are limited, and the molecular mechanisms of lipid biosynthesis in safflower seeds are not well understood. In this study, 11 oil-related quantitative traits and 50 pairs of InDel markers were used to assess the diversity of a collection of 605 safflower germplasms. The original safflower germplasm exhibited rich phenotypic diversity, with high variation for most of the phenotypic traits under investigation. Similarly, high genetic diversity was evaluated in the original germplasm, in which the mean Shannon's information index (I), observed heterozygosity (H0), and expected heterozygosity (He) were 0.553, 0.182, and 0.374, respectively. Four subgroups with strong genetic structures were identified and a core germplasm of 214 cultivars was constructed, which is well represented in the original germplasm. Meanwhile, differential expression analysis of the transcriptomes of high and low linoleic acid safflower varieties at two stages of seed development identified a total of 47 genes associated with lipid biosynthesis. High expression of the genes KAS II and SAD enhanced the synthesis and accumulation of oleic acid, while FAD genes like FAD2 (Chr8G0104100), FAD3, FAD7 and FAD8 promoted the consumption of oleic acid conversion. The coordinated regulation of these multiple genes ensures the high accumulation of oleic acid in safflower seed oil. Based on these findings, a core germplasm of 214 cultivars was constructed and 47 candidate genes related to unsaturated fatty acid biosynthesis and lipid accumulation were identified. These results not only provide guidance for further studies to elucidate the molecular basis of oil lipid accumulation in safflower seeds, but also contribute to safflower cultivar improvements.


Quantitative protein expression of blood-brain barrier transporters in the vasculature of brain metastases of patients with lung and breast cancer.
This study determined absolute transporter protein abundances in isolated microvessels of human noncancerous cerebral cortex as well as brain metastases of patients with lung and breast cancer, using a validated targeted proteomics approach. As compared with those in microvessels of noncancerous cerebral cortex, the median protein abundances of glucose transporter 1 (a brain endothelial marker) and sodium-potassium pump (Na/K ATPase, a plasma membrane marker) were decreased by ~ 80% in brain metastasis microvessels. The major efflux transporters (ABCB1 and ABCG2) fell to undetectable in microvessels of more than 80% of brain metastasis specimens. Monocarboxylate transporter 1 was undetectable in microvessels of more than 80% of brain metastases, whereas large neutral amino acid transporter 1 levels remained unchanged. In conclusion, the integrity of the physical and biochemical barrier with respect to transporter protein expression is largely disrupted in brain metastasis tumor vasculatures. Differential transporter protein abundances at the blood-brain barrier and blood-brain tumor barrier provided mechanistic and quantitative basis for prediction of heterogeneous drug penetration into human brain and brain tumors, which is critical not only to the understanding of the success or failure of systemic chemotherapy in the treatment of brain tumors but also to the development of more effective therapeutic strategies.


Reconceptualizing high-quality emergency general surgery care: Non-mortality-based quality metrics enable meaningful and consistent assessment.
Ongoing efforts to promote quality-improvement in emergency general surgery (EGS) have made substantial strides but lack clear definitions of what constitutes "high-quality" EGS care. To address this concern, we developed a novel set of five non-mortality-based quality metrics broadly applicable to the care of all EGS patients and sought to discern whether (1) they can be used to identify groups of best-performing EGS hospitals, (2) results are similar for simple versus complex EGS severity in both adult (18-64 years) and older adult (≥65 years) populations, and (3) best performance is associated with differences in hospital-level factors. Patients hospitalized with 1-of-16 American Association for the Surgery of Trauma-defined EGS conditions were identified in the 2019 Nationwide Readmissions Database. They were stratified by age/severity into four cohorts: simple adults, complex adults, simple older adults, complex older adults. Within each cohort, risk-adjusted hierarchical models were used to calculate condition-specific risk-standardized quality metrics. K-means cluster analysis identified hospitals with similar performance, and multinomial regression identified predictors of resultant "best/average/worst" EGS care. A total of 1,130,496 admissions from 984 hospitals were included (40.6% simple adults, 13.5% complex adults, 39.5% simple older adults, and 6.4% complex older adults). Within each cohort, K-means cluster analysis identified three groups ("best/average/worst"). Cluster assignment was highly conserved with 95.3% of hospitals assigned to the same cluster in each cohort. It was associated with consistently best/average/worst performance across differences in outcomes (5×) and EGS conditions (16×). When examined for associations with hospital-level factors, best-performing hospitals were those with the largest EGS volume, greatest extent of patient frailty, and most complicated underlying patient case-mix. Use of non-mortality-based quality metrics appears to offer a needed promising means of evaluating high-quality EGS care. The results underscore the importance of accounting for outcomes applicable to all EGS patients when designing quality-improvement initiatives and suggest that, given the consistency of best-performing hospitals, natural EGS centers-of-excellence could exist. Prognostic and Epidemiological; Level III.


Mechanical Properties of High-Volume Fly Ash Strain Hardening Cementitious Composite (HVFA-SHCC) for Structural Application.
Strain-hardening cementitious composite (SHCC) is a kind of construction material that exhibits multiple cracking and strain-hardening behaviors. The partial replacement of cement with fly ash is beneficial to the formation of the tensile strain-hardening property of SHCC, the increase of environmental greenness, and the decrease of hydration heat, as well as the material cost. This study aimed to develop a sustainable construction material using a high dosage of fly ash (no less than 70% of the binder material by weight). Based on the micromechanics analysis and particle size distribution (PSD) optimization, six mixes with different fly ash to cement ratios (2.4-4.4) were designed. The mechanical properties of the developed high-volume fly ash SHCCs (HVFA-SHCCs) were investigated through tensile tests, compressive tests, and flexural tests. Test results showed that all specimens exhibited multiple cracking and strain-hardening behaviors under tension or bending, and the compressive strength of the designed mixes exceeded 30MPa at 28 days, which is suitable for structural applications. Fly ash proved to be beneficial in the improvement of tensile and flexural ductility, but an extremely high volume of fly ash can provide only limited improvement. The HVFA-SHCC mix FA3.2 (with fly ash to binder ratio of about 76% by weight) designed in this study is suggested for structural applications.


The Nuclear Export Inhibitor Selinexor Inhibits Hypoxia Signaling Pathways And 3D Spheroid Growth Of Cancer Cells.
The nucleocytoplasmic transport of macromolecules is critical for both cell physiology and pathophysiology. Exportin 1 (XPO1), the major nuclear export receptor, is involved in the cellular adaptation to reduced oxygen availability by controlling the nuclear activity of the hypoxia-inducible factors (HIFs). Recently, a specific inhibitor of XPO1, selinexor (KPT-330), has been identified that inhibits nuclear export of cargo proteins by binding to the XPO1 cargo-binding pocket. We used different cancer cell lines from human tissues and evaluated the physiological activity of selinexor on the hypoxia response pathway in two-dimensional (2D) monolayer cell cultures in quantitative real-time (qRT)-PCR experiments and luciferase reporter gene assays. A three-dimensional (3D) tumor spheroid culture model of MCF-7 breast cancer cells was established to analyze the effect of selinexor on 3D tumor spheroid structure, formation and viability. Selinexor treatment reduces HIF-transcriptional activity and expression of the HIF-1 target gene solute carrier family 2 member 1 (SLC2A1). Moreover, 3D tumor spheroid structure, formation and viability are inhibited in response to selinexor-induced nuclear export inhibition. Here, we demonstrate the effect of specific XPO1-inhibition on the hypoxic response on the molecular level in 2D and 3D culture models of MCF-7 cells.


The association between a functional CYP1A1 polymorphism and colorectal neoplasia risk in post menopausal women.
The impact of estrogen on risk of colorectal neoplasia is uncertain. Carriers of the AA and CA genotype allele of the C4887A polymorphism of the CYP1A1 gene have enhanced estrogen metabolism relative to carriers of the CC genotype. This study examined whether this genetic marker of enhanced estrogen catabolism segregated with colorectal neoplasia (CRN) in postmenopausal women. We enrolled hormone negative postmenopausal women having screening or surveillance colonoscopy. Demographic and medical data were gathered. Blood was collected and analyzed for CYP1A1 polymorphisms of the C4887A allele by PCR-RFLP. Colonoscopy and pathology data were gathered from hospital databases. One hundred sixty-eight women were enrolled in the study. Twenty-one subjects (12.5%) carried at least one A allele, and 147 subjects (87.5%) carried the CC alleles for the C4887A polymorphism of the CYP1A1 gene. Seventy subjects (41.7%) had CRN and 98 subjects (58.3%) did not have CRN. Of the subjects who carried the A allele, 57% had CRN as compared to 39% of those who carried the CC allele; the association was not statistically significant (P = 0.16). In a multivariate logistic regression analysis, age, BMI, current tobacco use, and first degree relative with CRN were independent risk factors for CRN but the C4887A polymorphisms remained not statistically significant (P = 0.35). Carriers of the A allele of the C4887A polymorphism have enhanced estrogen catabolism and lower free estradiol. Our results suggest, however, that inherent estrogen metabolism as determined by C4887A polymorphisms is not associated with CRN risk.


[Screening for cancer. International knowledge and Danish practice].
Screening makes it possible to detect cancer before the disease gives rise to symptoms. A more effective treatment could thus be offered, and patients would then have a better prognosis. If screening works, mortality from a given cancer disease should decline in the screened population. At present three screening tests meet this requirement: 1) Pap smears for cervical dysplasia, with screening started at the latest at the age of 30 and not before the age of 20; 2) Mammography screening for breast cancer in women aged 50-69; and 3) faecal occult blood testing for colorectal cancer in men and women aged 50-74. But screening means the testing of healthy persons for cancer, and it therefore has a number of negative side effects, such as false positive and false negative tests. Whether or not screening is preferable in a given situation therefore depends on how the advantages are weighted against the disadvantages.


Intralingual Administration of AAVrh10-miRSOD1 Improves Respiratory But Not Swallowing Function in a Superoxide Dismutase-1 Mouse Model of Amyotrophic Lateral Sclerosis.
Amyotrophic lateral sclerosis (ALS) is a fatal disease characterized by degeneration of motor neurons and muscles, and death is usually a result of impaired respiratory function due to loss of motor neurons that control upper airway muscles and/or the diaphragm. Currently, no cure for ALS exists and treatments to date do not significantly improve respiratory or swallowing function. One cause of ALS is a mutation in the superoxide dismutase-1 (SOD1) gene; thus, reducing expression of the mutated gene may slow the progression of the disease. Our group has been studying the SOD1G93A transgenic mouse model of ALS that develops progressive respiratory deficits and dysphagia. We hypothesize that solely treating the tongue in SOD1 mice will preserve respiratory and swallowing function, and it will prolong survival. At 6 weeks of age, 11 SOD1G93A mice (both sexes) received a single intralingual injection of gene therapy (AAVrh10-miRSOD1). Another 29 mice (both sexes) were divided into two control groups: (1) 12 SOD1G93A mice that received a single intralingual vehicle injection (saline); and (2) 17 non-transgenic littermates. Starting at 13 weeks of age, plethysmography (respiratory parameters) at baseline and in response to hypoxia (11% O2) + hypercapnia (7% CO2) were recorded and videofluoroscopic swallow study testing were performed twice monthly until end-stage disease. Minute ventilation during hypoxia + hypercapnia and mean inspiratory flow at baseline were significantly reduced (p < 0.05) in vehicle-injected, but not AAVrh10-miRSOD1-injected SOD1G93A mice as compared with wild-type mice. In contrast, swallowing function was unchanged by AAVrh10-miRSOD1 treatment (p > 0.05). AAVrh10-miRSOD1 injections also significantly extended survival in females by ∼1 week. In conclusion, this study indicates that intralingual AAVrh10-miRSOD1 treatment preserved respiratory (but not swallowing) function potentially via increasing upper airway patency, and it is worthy of further exploration as a possible therapy to preserve respiratory capacity in ALS patients.


Low thymidylate synthase expression in the primary tumor predicts favorable clinical outcome in resected gastric cancer patients treated with adjuvant tegafur.
To assess the thymidylate synthase protein (TS) in tumor cells of resected gastric cancer patients treated with adjuvant tegafur (TG), we reviewed the outcome of 94 randomized patients treated either with adjuvant TG plus mitomycin C (MMC) or MMC alone. TS was determined in 76 out of 94 patients, previously randomized to receive adjuvant TG, 500 mg/m(2)/day p.o. for 6 months plus four courses of MMC, 10- 20 mg/m(2) i.v. every 6 weeks or MMC alone. An immunohistochemical assessment with the monoclonal antibody TS-106 was performed. Low TS was observed in 38 patients (20 treated with TG-MMC and 18 with MMC) and high TS in the other 38 patients (21 treated with TG-MMC and 17 with MMC). After 10 years' median follow-up time, 61% of adjuvant TG-MMC patients and 43% of MMC patients were alive and disease-free. Disease-free survival and overall survival were significantly better for patients treated with TG-MMC compared to MMC adjuvant (p = 0.0277 and p = 0.05), and low-TS compared to high-TS patients (p = 0.0184 and p = 0.0198). In 38 low-TS patients we observed an 83% chance to be disease-free in TG-MMC-treated patients and 55% in MMC-treated patients (p = 0.04). A low TS level determines a subset of patients that may benefit from adjuvant oral TG when added to MMC showing a 5-year cure rate of more than 80%.


Differential Expression Patterns of Toll-like Receptors in COVID-19 Patients.
Since Toll-like receptors (TLRs) recognize the earliest signs of infection or cell damage, they play fundamental roles in innate immunity. This review summarizes the numerous studies on the expression of TLRs in patients with Coronavirus disease 2019 (COVID-19). We show that infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can stimulate at least six of the ten TLRs in humans and that this can shape the severity of COVID-19. Specifically, TLR2, TLR4, and TLR9 appear to play pathogenic roles while TLR3, TLR7, and TLR8 may be protective. Most have mutations that could partly explain the susceptibility phenotypes of COVID-19. Further understanding the roles of TLRs in COVID-19 immunopathogenesis could reveal prognostic biomarkers and help drive the development of novel and effective therapeutics for COVID-19.