A rare cause of hypertension in children: intrathoracic pheochromocytoma.
Mediastinal pheochromocytomas account for only a small fraction of mediastinal tumors. Most commonly, these tumors are located in posterior mediastinum. Increasing number of cases of pheochromocytomas is being reported from middle mediastinum. Excision of mediastinal paraganglioma is often hazardous because of its rich blood supply and tendency to involve surrounding structures. It can be a big challenge to manage asymptomatic cases of pheochromocytoma intraoperatively. It is imperative that these patients receive adequate alpha adrenergic and if necessary beta adrenergic blockade. Adequate preoperative preparation with alpha and beta blockers may not prevent serious intraoperative hypertension. We report a case of posterior mediastinal pheochromocytoma which was biochemically active preoperatively. We review the presentation, diagnosis and management of intrathoracic pheochromocytomas including cardiac pheochromocytomas.


Involvement of platelets in tumor cell metastasis.
Extensive experimental evidence indicates that platelets contribute to tumor cell proliferation and metastasis through direct interactions and secreted bioactive proteins. Activated platelets release secretory factors that promote growth factors, chemokines, proangiogenic regulatory proteins, proteolytic enzymes and microparticles within the microenvironment to promote tumor cell growth and invasion. Furthermore, the formation of platelet-tumor cell heteroaggregates by integrin αIIbβ3 (glycoprotein IIb/IIIa) bridging plays an important role in tumor survival by forming a physical shield around tumor cells, and thereby protecting circulating tumor cells from immune-mediated lysis by natural killer (NK) cells. Tumor cells directly activate platelets by enhancing expression of surface integrins, selectins and secretion of granules, which amplify platelet aggregation. In addition to the physical coating of tumor cells, platelets release transforming growth factor-β1 (TGF-β1) that induces phenotypic changes of epithelial to mesenchymal-like transition of tumor cells, thereby facilitating their extravasation and dissemination to distant sites during metastasis. Thus, there is a complex interplay between platelet-induced tumor growth and tumor cell-induced platelet activation, with the involvement of multiple components within the tumor microenvironment that enhance metastasis. This review describes the intimate reciprocal cross-talk between platelets and tumor cells, and the various signaling pathways involved in tumor amplification, which may be potential therapeutic targets to disrupt the platelet-tumor loop to reduce metastatic processes.


[The innovation and change processes: an update on background theories].
The innovation and change processes: an update on background theories. The change process was widely studied to improve its understanding and management. To synthesize the theoretical debate on organizational change, on the reactions of those involved and on the strategies suggested to manage it. The drive to change may come from factors internal or external to the organization. The aim of the change can be oriented to the adaptation or to a radical change; the worries of those involved span from its personal to professional impact. The guarantee of a support during the change process is especially important when several wards are involved and when a reallocation or transfer of resources has been planned.


Response to pneumococcal polysaccharide vaccine in children with asthma, and children with recurrent respiratory infections, and healthy children.
To analyse specific immune response to the 23-valent pneumococcal polysaccharide vaccine by measuring pneumococcal antibodies in children with asthma and with respiratory recurrent infection (RRI) as compared to healthy children. The study included 60 children, divided into three groups: 20 with asthma, 20 with RRI, and 20 healthy controls. Post-vaccination specific IgG antibodies against 10 pneumococcal serotypes (S1, S3, S4, S5, S6B, S9V, S14, S18C, S19F, and S23F) contained in the 23-valent pneumococcal polysaccharide vaccine (PPV) were measured. A specific IgG concentration ≥1.3μg/mL was considered a protective response to the vaccine. For statistical analysis, levels of specific IgG antibodies against each of the 10 pneumococcal serotypes were compared across the three groups of children using the x(2) test. All of the children showed antipneumococcal antibody levels >1.3μg/mL for over 70% of the serotypes, considered within the normal range of response. Average IgG antibody levels and percentages of children protected were statistically comparable among the three groups studied. The asthmatic children without RRI had pneumococcal antibody levels and percentages of serotype-specific protection to PPV comparable to those of healthy children. Asthmatic children with recurrent infections should be evaluated for specific antibody deficiency (SAD). Because asthma patients are at high risk for invasive pneumococcal infections, it would be worthwhile to explore systematic administration of PPV in children over the age of two years who have not received a pneumococcal conjugate vaccine, considering the positive response to PPV reported here.


Electronic healthcare applications and programs among healthcare workers in Riyadh and conflict management.
Electronic healthcare applications and programmes enable the use of computers, networks, and information technology to improve healthcare quality and patient safety, and secure confidential access to health information in order to enable individuals and communities to make the best possible health decisions. We study conflicts challenging users of e-health electronic applications and programmes in Riyadh. We use a cross-sectional descriptive design to target all healthcare professionals who interact with e-health applications and programmes. Healthcare providers took a questionnaire survey online. Of the 169 responses to our questionnaire, 78.1% are female, and 46.2% are aged between 31 and 40 years. As many as 59.2% always use these applications, and 33.7% use them occasionally. Only 7.10% of the participants rarely or never use them. As many as 31.4% recognized that these applications led to conflicts at the workplace. Of these, 50.6%, 13.6%, and 35.8% stated that they caused decision-related, ethical, and other types of conflicts, respectively. We conducted this study among healthcare providers in Riyadh, KSA, and found that the use of e-health applications and programmes encountered some difficulties.


Major depressive disorder: a prospective study of residual subthreshold depressive symptoms as predictor of rapid relapse.
The study tested whether level of recovery from major depressive episodes (MDEs) predicts duration of recovery in unipolar major depressive disorder (MDD) patients. MDD patients seeking treatment at five academic centers were followed naturalistically for 10 years or longer. Patients were divided on the basis of intake MDE recovery into residual depressive symptoms (SSD; N=82) and asymptomatic (N=155) recovery groups. They were compared on time to first episode relapse/recurrence, antidepressant medication, and comorbid mental disorders. Recovery level was also compared to prior history of recurrent MDEs ( > 4 lifetime episodes) as a predictor of relapse/recurrence. Residual SSD compared to asymptomatic recovery patients relapsed to their next MDE > 3 times faster (median=68 vs. 23 weeks) and to any depressive episode > 5 times faster (median=33 vs. 184 weeks). Residual SSD recovery status was significantly associated with early episode relapse (OR=3.65) and was stronger than history of recurrent MDEs (OR=1.64). Rapid relapse in the SSD group could not be attributed to higher comorbidity or lower antidepressant treatment. Although inter-rater agreement on weekly depressive symptom ratings was very high (ICC > 0.88), some error may exist in assigning recovery levels. Antidepressant treatments were recorded, but were not controlled. MDE recovery is a powerful predictor of time to episode relapse/recurrence. Residual SSD recovery is associated with very rapid episode relapse which supports the idea that SSD is an active state of illness. Asymptomatic recovery is associated with prolonged delay in episode recurrence. These findings of this present study have important implications for the goals of treatment of MDD and for defining true MDE recovery.


The involvement of caspase-11 in TPEN-induced apoptosis.
The depletion of intracellular zinc with N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) induces protein synthesis-dependent apoptosis. Here we examined the involvement of caspase induction in apoptosis. Among the examined caspases, only caspase-11 was increased by TPEN. Caspase-11 activity also increased, which resulted in caspase-3 activation. Cycloheximide or actinomycin D blocked caspase-11 induction, reduced caspase-11 and -3 activation, and attenuated TPEN-induced neuronal apoptosis. Blockade of caspase-11 by a chemical inhibitor or genetic deletion attenuated TPEN-induced apoptosis, indicating a critical role of caspase-11 in TPEN-induced apoptosis. Although mitochondria-mediated caspase-9/-3 activation also contributed to TPEN-induced apoptosis, caspase-11 is likely a key inducible apoptosis-inducing protein.


Power of the process: evaluating the impact of the Framework Convention on Tobacco Control negotiations.
Evaluate the impact of the FCTC negotiations on the diffusion of tobacco control policies. Analyzed country characteristics to determine their effects on the frequency, type and strength of tobacco control policies adopted among WHO Member States. Bivariate analyses were conducted for each characteristic to compare the frequency and strength of control policies adopted between pre-negotiation and negotiation periods. Multivariate regression analyses were performed to determine the predictive nature of these variables. The frequency of policy adoption intensified during the years the FCTC negotiations were most intense. The strength of policies adopted also shifted significantly towards policies promoted by WHO. The average strength of policies adopted varied significantly according to country characteristics. All characteristics, with the exception of total and male smoking prevalence, were significantly associated with the number of policy types adopted. This study suggests that investments in international legal processes can be effective, even when the outcomes are unclear from the start. The FCTC negotiation process coincided with a rise in domestic policy adoption in the direction advocated by WHO. However, there remains a need to improve outreach and diffusion to lower-income countries in tobacco control, as well as other areas of chronic disease control.


Phase Engineering of Molybdenum Carbide/Oxide for Highly-Efficient Electrocatalytic Hydrogen Production.
Molybdenum carbide is one of non-precious metal materials and it is a promising electrocatalyst for hydrogen production. Synthesis and improvement of molybdenum carbide's catalytic performance is of great significance. Herein, carbon-based Mo2 C with hybrid phase of MoO2 was fabricated by matching the composition of Mo and C derived from pomelo peel and optimizing raw carbon amount and prolysis temperature. The resulting MoO2 /Mo2 C@C is composed of loose microspheres with mesoporous microstructure and is self-assembled from nanoparticles. The results show that MoO2 /Mo2 C@C2 material exhibits excellent HER performance and only a low overpotentials of 143 mV is needed to drive the current density of 10 mA cm-2 in alkaline solution, and Tafel slopes are only 63.4 mV dec-1 , respectively. Notably, it has potential application at low overpotentials to drive large current density and this strategy also provides a universal route to prepare non-noble metal catalyst with hybrid phase of oxide/carbide.


Diabetes awareness and diabetes risk reduction behaviors among attendance of primary healthcare centers.
The aims of this study were to assess level of awareness about diabetes and the level of adoption of diabetes risk behaviors among adult attending primary healthcare centers. A cross-sectional descriptive study was conducted using a self-administrated questionnaire. In addition to demographic information, the questionnaire contained questions on diabetes awareness related to diabetes definition, symptoms, risk factors, complications and management of diabetes as well as questions on diabetes risk reduction behaviors and sources of information on diabetes. The data was analyzed with independent t-test, Pearson's correlation coefficient, and ANOVA test. A total of 541 participants aged ≥ 18 years were recruited. The mean score of diabetes awareness was 27.5/40 [SD=5.7]. The participants performed best in symptoms section with a mean score of 6.3/8 [SD=1.6], and worst in the risk factors section with a mean score of 3.6/6 (SD=1.4). With respect to diabetes risk reduction behaviors the results showed that the highest mean score was for fat reduction 2.0/4 [SD=0.8]; and the lowest mean score was for weight control or losing 1.7/4 [SD=0.8]. The current study demonstrated that substantial numbers of adult Jordanian lack the sufficient awareness about diabetes to prevent and cope with the increasing prevalence of diabetes in Jordan. Also, it demonstrated that adoption of diabetes risk reduction behaviors was suboptimal. Raising public awareness of diabetes and diabetes risk reduction behaviors through population-based programs and mass media should be planned and implemented.


Elucidation of fatty acid profiles in vegetable oils exploiting group-type patterning and enhanced sensitivity of comprehensive two-dimensional gas chromatography.
The present research is focused on the use of comprehensive 2-D GC (GCxGC) for the thorough elucidation of fatty acid (FA) profiles contained in vegetable oils; the samples analysed consisted of extra-virgin olive oil and refined hazelnut oil. The enhanced sensitivity and the formation of group-type patterns provided by GCxGC enabled the identification and quantification of both well-known and rather unexpected FAs contained in the lipid matrices. Peak assignment was, in most cases, supported by using pure standard compounds. Of particular interest was the identification of a series of odd-numbered FAs in both samples. The results attained to demonstrate the usefulness of GCxGC also for the analysis of supposedly low-complex samples.


The role of spider cocoons in controlling desiccation.
The abilities of the cocoons of the spiders Mecynogea lemniscata and Argiope aurantia to protect the enclosed egg and spiderling stages from desiccation were investigated in the laboratory under controlled humidities, and in the field under ambient conditions. For M. lemniscata, which has a relatively small clutch (8-30 eggs) and remains in the cocoon for approximately 9-10 months, removal of the cocoon had no effect on water loss from the egg stage, nor did it adversely affect hatching or molting success. Cocoon removal did, however, significantly affect water loss and, consequently, survival in the spiderling stage at all humidities in the laboratory and in the field. The importance of the cocoon for survival is probably related to the unusually long time M. lemniscata spiderlings spend in the cocoon overwintering. For A. aurantia, which has a substantially larger clutch size (300-1400 eggs) and remains in the cocoon for a shorter 6-7 months, cocoon removal had no effect on water loss, egg hatching success, molting success, nor spiderling survival. The lack of an effect suggests that other factors (e.g., relative humidity at the oviposition site, or a large clutch size) may be more important in controlling water loss for A. aurantia.


Description of a new water mite species of the genus Lebertia Neuman, 1880 (Acari, Hydrachnidia: Lebertiidae) from Kazakhstan.
A new water mite species of the subgenus Septlebertia Imamura, 1954, Lebertia boldyrbekensis sp. n. is described from running waters in the Republic of Kazakhstan. An identification key for all species of the subgenus Septlebertia is presented.


Clavipectoral plane block as a sole anesthetic technique for clavicle surgery - A case report.
The clavipectoral fascial plane block was introduced by Dr. Luis Valdes in a symposium at the 2017 European Society of Regional Anesthesia and Pain Therapy Congress. Clavipectoral plane block (CPB) with intravenous sedation provided surgical anesthesia and analgesia in a 39-year-old male patient with a right midshaft clavicle fracture. This in-plane technique was used to deposit 30 ml of a local anesthesia mixture between the clavipectoral fascia and periosteum on both the medial and lateral sides of the fracture line. Excellent anesthesia and analgesia for up to 16 h post-block were provided by CPB during the clavicle surgery.


Clinical characteristics and prognostic model for extensive-stage small cell lung cancer: A retrospective study over an 8-year period.
Small cell lung cancer (SCLC) is a highly aggressive neuroendocrine tumor with a short replication time and a rapid growth rate. Prognostic factors for SCLC in clinical practice are scarce. Retrospective analysis of 8-year extensive-stage SCLC data from the Department Respiratory and Intensive Care Unit, Peking Union Medical College Hospital (Beijing, China) was performed to develop a risk prediction model that can facilitate the identification of extensive-stage SCLC with differing prognosis in clinical practice. A retrospective analysis of data from patients with extensive-stage SCLC at a single-center from January 2013 to January 2021, including age, sex, ECOG physical score, immunohistochemistry (CgA, Syn, CD56, TTF1, and Ki67), staging, treatment regimen, laboratory examinations, and survival period, was performed. Clinical variables with potential prognostic significance were screened by univariate Cox analysis. Next, multifactor Cox risk prediction regression analysis was performed to establish an extensive-stage SCLC risk prognostic model. Survival curves and ROC curves for high and low risk groups were plotted according to risk scores. Nomogram and calibration curves were developed to assess the accuracy of the risk prediction model. This study included 300 patients who were diagnosed with extensive-stage SCLC at our center from January 2013 to January 2021. The most common first presentation was respiratory symptoms, especially cough (162, 54%). The most common extra-thoracic metastatic organs were bone (36.3%), liver (24.7%), brain (15.7%), and adrenal glands (15.7%). A total of 99% of patients received first-line systemic therapy, with 86.3% of patients treated with platinum-etoposide and 10.7% of patients treated with immune checkpoint inhibitor combined with platinum-etoposide backbone. First-line progression-free survival was up to 198 days, and the median OS was 439 days. After Cox regression screening and backward stepwise selection, "time from initial therapy to relapse or progression (PFS1), liver metastases, adrenal metastases, M stage and first-line treatment pattern" were retained to establish a prognostic model with an AUC value of 0.763. The prognostic model was shown as a nomogram with good agreement between predicted and observed outcomes. The first-line treatment of SCLC patients admitted to our hospital in the past 8 years was relatively standardized, and the progression-free survival and OS were slightly longer than those reported in the literature. We developed a prognostic risk score model for extensive-stage SCLC to calculate individual survival in clinical practice.


Improving pancreatic islet in vitro functionality and transplantation efficiency by using heparin mimetic peptide nanofiber gels.
Pancreatic islet transplantation is a promising treatment for type 1 diabetes. However, viability and functionality of the islets after transplantation are limited due to loss of integrity and destruction of blood vessel networks. Thus, it is important to provide a proper mechanically and biologically supportive environment for enhancing both in vitro islet culture and transplantation efficiency. Here, we demonstrate that heparin mimetic peptide amphiphile (HM-PA) nanofibrous network is a promising platform for these purposes. The islets cultured with peptide nanofiber gel containing growth factors exhibited a similar glucose stimulation index as that of the freshly isolated islets even after 7 days. After transplantation of islets to STZ-induced diabetic rats, 28 day-long monitoring displayed that islets that were transplanted in HM-PA nanofiber gels maintained better blood glucose levels at normal levels compared to the only islet transplantation group. In addition, intraperitoneal glucose tolerance test revealed that animals that were transplanted with islets within peptide gels showed a similar pattern with the healthy control group. Histological assessment showed that islets transplanted within peptide nanofiber gels demonstrated better islet integrity due to increased blood vessel density. This work demonstrates that using the HM-PA nanofiber gel platform enhances the islets function and islet transplantation efficiency both in vitro and in vivo.


DNA delivery from an intravascular stent with a denatured collagen-polylactic-polyglycolic acid-controlled release coating: mechanisms of enhanced transfection.
We previously demonstrated that DNA-polylactic-polyglycolic acid (PLGA)-coated stents can deliver genes to the arterial wall with reporter expression involving 1% of neointimal cells. The present study investigated a novel formulation utilizing denatured collagen in DNA-stent coatings; denatured collagen was hypothesized to enhance gene transfer due to adhesion molecule interactions and actin-related mechanisms. Arterial smooth muscle cells (SMCs) cultivated on denatured collagen had significantly greater plasmid DNA (beta-galactosidase) transfection than SMC grown on native collagen (18.3+/-1.2 vs 1.0+/-0.1%, P<0.001). The denatured-collagen effect was completely blocked with anti-alpha(v)beta(3) integrin antibody. SMCs cultivated on native collagen supplemented with tenascin-C (TN-C), a protein recognized by alpha(v)beta(3) integrins, showed a 33-fold increase in transfection compared to control (P<0.001); this effect was also blocked with anti-alpha(v)beta(3) antibody. We observed that cells grown on denatured collagen had marked F-actin-enriched stress fibers and intense perinuclear G actin, compared to those grown on native collagen, which demonstrated F-actin-enriched focal adhesions without perinuclear G-actin localization. Cytochalasin-D, an F actin depolymerizing agent, caused significantly increased SMC transfection in cells cultivated on native collagen compared to control cells (18.0+/-1.8 vs 3.02+/-0.9%, P<0.001) further supporting the view that actin-related cytoskeletal changes influence transfection. A denatured-collagen-PLGA composite vascular stent coating similarly resulted in increased plasmid DNA green fluorescent protein (GFP) expression compared to controls (P<0.001) in SMC cultures; the increased transfection was blocked by anti-alpha(v)beta(3) antibody. Pig coronary studies comparing denatured-collagen-PLGA-coated stents containing plasmid DNA (encoding GFP) to coated stents without DNA demonstrated 10.8% of neointimal cells transfected; this level of expression was almost an order of magnitude greater than previously reported with a DNA delivery stent. It is concluded that denatured collagen incorporated into plasmid DNA-stent coating formulations may increase the level of gene expression in vitro and in vivo because of integrin-related mechanisms and associated changes in the arterial smooth muscle cell actin cytoskeleton.


Structural analysis of the ridge count data of Australian Europeans using multivariate analysis.
Multivariate analyses are used to study the structural patterns of ridge counts of fingers. There is a significant difference between the ridge counts of two hands, chiefly due to the first and fourth fingers. There is asymmetry in the covariance matrix of the ridge counts. The correlations between fingers are significant and the decrease in correlation with increasing distance between fingers is not significant.


Shape distortion in sintering results from nonhomogeneous temperature activating a long-range mass transport.
Sintering theory predicts no long-range mass transport or distortion for uniformly heated particles during particle coalescence. However, in sintering-based manufacturing processes, permanent part distortion is often observed. The driving forces and mechanisms leading to this phenomenon are not understood, and efforts to reduce distortion are largely limited to a trial-and-error approach. In this paper, we demonstrate that distortion during sintering results from mass-transport driven by nonhomogeneous temperature distribution. We then show that hitherto unknown mass transport mechanisms, working in the direction opposite to temperature gradient are the likely cause of distortion. The experimental setup, designed for this purpose, enables the quantification of distortion during sintering. Two possible mass transport mechanisms are defined, and the continuum model applicable to both is formulated. The model accurately predicts the transient and permanent distortion observed during experiments, including their size dependence. Methods to control distortion that can give rise to 4D printing are discussed.


A preliminary exploration of experiences of integrating the body in the self in two women with anorexia nervosa in view of phenomenological conceptualisations.
People with anorexia nervosa often present with confusions around bodily sensations and difficulties in experiencing their body as a place of their own. Many existing models understand anorexia nervosa as a disorder of behaviour and thoughts about eating and body size, and treatments typically focus on modifying thoughts and psychological processes. They leave aside the subject as she experiences the body from a first-person perspective. Inspired by phenomenology and the embodied mind thesis, this explorative study examines in depth the experiences of individuals with anorexia nervosa as they engage in Norwegian psychomotor physiotherapy. Through release of bodily tension and restricted breathing, this method aims to help subjects tune into the body and accept that difficult experiences, relationships and feelings are also bodily. Qualitative in-depth interviews were conducted with two women who had been attending Norwegian psychomotor physiotherapy for more than two years. Thematic analysis was used to identify, analyse and interpret themes within the data. Three main overarching themes that structure the subjects' experiences were identified: the meaning of the therapeutic relationship, changes in bodily connectedness and ways of moving, and improved ability to articulate and reflect on feelings. The subjects described a greater tendency to experience the body in the self and as a place of their own, a more flexible and vital body, and an increased capacity to identify, express and make sense of feelings. These changes enriched their interactions with the social world. Feeling acknowledged and accepted by the therapist throughout the process was essential. The study illustrates how difficult experiences, thoughts and feelings can, over time, manifest in the body as withheld breathing and diverse bodily constraints affecting both self- and body awareness. The study endorses the phenomenological concepts that our experiences of the self and the world are essentially bodily, and emphasizes the importance of the first-person perspective when investigating the contribution of the body to the self and to our interactions with the social world. Physio- and body awareness therapies that help patients relate to, understand and integrate bodily experiences may complement other treatment approaches and help patients with anorexia proceed with the recovery process. Having anorexia nervosa involve changes in the way one experiences the body. The condition has been linked to confusions around bodily sensations and reduced experience of the body as an integrated place of their own. The purpose of this study was to gain a richer understanding of bodily experiences in subjects with anorexia nervosa having attended a specialized physiotherapy approach. In depth interviews were conducted with two women who had anorexia nervosa and who had engaged in Norwegian Psychomotor Physiotherapy for more than two years. Three themes that structure the subjects' experiences were identified: the meaning of the therapeutic relationship, changes in bodily connectedness and ways of moving, and improved ability to articulate and reflect on feelings. The subjects described a greater tendency to experience the body in the self and as a place of their own, a more flexible and vital body, and an increased capacity to identify, express and make sense of feelings. Feeling acknowledged and accepted by the therapist throughout the process was essential. The study illustrates how difficult experiences, thoughts and feelings can manifest in the body as withheld breathing and diverse bodily constraints affecting both self- and body awareness in people with anorexia nervosa.


Attenuation of edema and infarct volume following focal cerebral ischemia by early but not delayed administration of a novel small molecule KDR kinase inhibitor.
Vascular endothelial growth factor (VEGF) may mediate increases in vascular permeability and hence plasma extravasation and edema following cerebral ischemia. To better define the role of VEGF in edema, we examined the effectiveness of a novel small molecule KDR kinase inhibitor Compound-1 in reducing edema and infarct volume following focal cerebral ischemia in studies utilizing treatment regimens initiated both pre- and post-ischemia, and with study durations of 24-72 h. Rats were subjected to 90 min of middle cerebral artery occlusion (MCAO) followed by reperfusion. Pretreatment with Compound-1 (40 mg/kg p.o.) starting 0.5h before occlusion significantly reduced infarct volume at 72 h post-MCAO (vehicle, 194.1+/-22.9 mm(3) vs. Compound-1, 127.6+/-22.8mm(3) and positive control MK-801, 104.4+/-22.6mm(3), both p<0.05 compared to vehicle control), whereas Compound-1 treatment initiated at 2h after occlusion did not affect infarct volume. Compound-1 pretreatment also significantly reduced brain water content at 24h (vehicle, 80.3+/-0.2% vs. Compound-1, 79.7+/-0.2%, p<0.05) but not at 72 h after MCAO. These results demonstrate that early pretreatment administration of a KDR kinase inhibitor elicited an early, transient decrease in edema and subsequent reduction in infarct volume, implicating VEGF as a mediator of stroke-related vascular permeability and ischemic injury.


Enhanced absorption and tissue distribution of paclitaxel following oral administration of DHP 107, a novel mucoadhesive lipid dosage form.
This study was conducted to examine the absorption and tissue distribution characteristics of paclitaxel-loaded DHP 107, a Cremophor EL-free, mucoadhesive lipid oral dosage form. DHP 107 was orally administered to mice at 10, 20 and 40 mg/kg doses. For comparison purposes, Taxol was i.v. injected at 5, 10 and 20 mg/kg doses. Drug levels were determined in plasma and tissues by validated HPLC assays. The absolute bioavailability and the relative distribution to various tissues were calculated as a function of dose. The dose-normalized plasma AUC(DHP 107)/AUC(Taxol) ratios calculated at comparable AUC values ranged from 14.6 to 29.0%. In contrast, relative tissue distribution ratios calculated as the dose-normalized AUC(DHP 107)/AUC(Taxol) were as high as 342.0, 139.0, 112.9 and 108.2% for stomach, small intestine, large intestine and ovary, respectively. Oral administration of DHP 107 provided a substantial systemic absorption of paclitaxel. Furthermore, the relative distribution ratios of DHP 107 at doses of 20 and 40 mg/kg were higher for stomach, small intestine, large intestine, and ovary than the systemic bioavailability, providing a basis for therapeutic advantages.


Nordic Walking Improves Cardiometabolic Parameters, Fitness Performance, and Quality of Life in Older Adults With Type 2 Diabetes.
To assess the effect of Nordic walking (NW) on cardiometabolic health, physical performance, and well-being in sedentary older adults with type 2 diabetes (T2D). Fifteen subjects with T2D (female, 5; male, 10; age, 65 ± 6.2 years [mean ± standard deviation]; body mass index, 27.3 ± 4.9 kg/m2 [mean ± standard deviation]) were enrolled in a 6-month NW training program. The fasting glucose and glycosylated hemoglobin levels, lipid profile (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides), systolic blood pressure (SBP), and diastolic blood pressures were measured before and after the intervention. Participants' quality of life (Short-Form Health Survey) and physical fitness (6-minute walking test) were also evaluated. Compared with baseline, NW significantly improved the fasting glucose level (103.5 ± 18.5 vs 168.7 ± 37.7 mg/dL, P = .01), SBP (121.8 ± 12.2 vs 133 ± 14.4 mm Hg, P = .02), physical fitness (759.88 ± 69 vs 615.5 ± 62.6 m, P < .001), and both mental health (54.5 ± 4.4 vs 45.7 ± 5.6, P < .01) and physical health (49.8 ± 4.7 vs 40.3 ± 5.9, P < .01). The levels of glycosylated hemoglobin (6.15% ± 0.8% vs 6.4% ± 1%, P = .46), total cholesterol (162.2 ± 31.2 vs 175.5 ± 28.8 mg/dL, P = .13), low-density lipoprotein cholesterol (95.2 ± 24.2 vs 106.3 ± 32.3 mg/dL, P = .43), and triglycerides (135.5 ± 60.8 vs 127.6 ± 57.4 mg/dL, P = 0.26) improved without reaching significance. NW training improved the glycemic levels, SBP, physical fitness, and perception of quality of life in older adults with T2D. NW represents a suitable complementary strategy to improve the global health status in this population.


Medial meniscal extrusion greater than 4 mm reduces medial tibiofemoral compartment contact area: a biomechanical analysis of tibiofemoral contact area and pressures with varying amounts of meniscal extrusion.
The primary objective of this study is to evaluate the contact areas, contact pressures, and peak pressures in the medial compartment of the knee in six sequential testing conditions. The secondary objective is to establish how much the medial meniscus is able to extrude, secondary to soft tissue injury while keeping its roots intact. Ten cadaveric knees were dissected and tested in six conditions: (1) intact meniscus, (2) 2 mm extrusion, (3) 3 mm extrusion, (4) 4 mm extrusion, (5) maximum extrusion, (6) capsular based meniscal repair. Knees were loaded with a 1000-N axial compressive force at 0°, 30°, 60°, and 90° for each condition. Medial compartment contact area, average contact pressure, and peak contact pressure data were recorded. When compared to the intact state, there was no statistically significant difference in medial compartment contact area at 2 mm of extrusion or 3 mm of extrusion (n.s.). There was a statistically significant decrease in contact area compared to the intact state at 4 mm (p = 0.015) and maximum extrusion (p < 0.001). The repair state was able to improve medial compartment contact area, and there was no statistically significant difference between the repair and the intact states (n.s.). No significant differences were found in the average contact pressure between the repair, intact, or maximum extrusion conditions at any flexion angle (n.s.). No significant differences were found in the peak contact pressure between the repair, intact, or maximum extrusion conditions at any flexion angle (n.s.). In this in vitro model, medial meniscus extrusion greater than 4 mm reduced medial compartment contact area, but meniscal extrusion did not significantly increase pressure in the medial compartment. Additionally, meniscal centralization was effective in restoring the medial tibiofemoral contact area to intact state when the meniscal extrusion was secondary to meniscotibial ligament injury. The diagnosis of meniscal extrusion may not necessarily involve meniscal root injury. Since it is known that meniscal extrusion greater than 3 or 4 mm has a biomechanical impact on tibiofemoral compartment contact area and pressures, specific treatments can be established. Centralization restored medial compartment contact area to the intact state.


Variation in DNAH1 may contribute to primary ciliary dyskinesia.
Primary Ciliary Dyskinesia (PCD) is a genetically heterogeneous ciliopathy caused by ultrastructural defects in ciliary or flagellar structure and is characterized by a number of clinical symptoms including recurrent respiratory infections progressing to permanent lung damage and infertility. Here we describe our search to delineate the molecular basis in two affected sisters with clinically diagnosed PCD from a consanguineous Saudi Arabian family, in which all known genes have been excluded. A homozygosity mapping-based approach was utilized that ultimately identified one single affected-shared region of homozygosity using 10 additional unaffected family members. A plausible candidate gene was directly sequenced and analyzed for mutations. A novel homozygous missense aberration (p.Lys1154Gln) was identified in both sisters in the DNAH1 gene that segregated completely with the disease phenotype. Further confirmation of this interesting variant was provided by exome-wide analysis in the proband. Molecular variation in DNAH1 may play a role in PCD and its potential contribution should be considered in patients where all known genes are excluded.


Supply chain needs improvement.
Other businesses rely on information technology to make the supply chain more efficient and dependable. Hospitals should follow suit.


Methylated Septin9 identified patients with colorectal carcinoma and showed higher sensitivity than conventional biomarkers in detecting tumor.
It is worth noting the limitations in sensitivity of the existing biomarkers carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in detection of colorectal cancer (CRC). In our study, we address the performance of the liquid biopsy biomarker "methylated septin 9" (mSEPT9) in the detection and disease surveillance of CRC. The monocentric prospective survey encompassed 120 patients diagnosed with CRC who underwent planned curative resection between December 2018 and December 2020. Blood samples were collected from the participants preoperatively as well as at 7 days, 6 weeks, and 3 months postoperatively. The presence of mSEPT9, CEA, and CA 19-9 was detected using the pro Epi Colon® 2.0 CE test, Elecsys® CEA, and Elecsys® CA19-9 electrochemiluminescence immunoassay, respectively. In the preoperative setting, mSEPT9 demonstrated superior capability in identifying patients with CRC compared to CEA and CA 19-9, with detection rates of 57%, 32%, and 18% respectively. Combining all three biomarkers increased the overall sensitivity to 66% preoperatively. In considering UICC stage and T-status, mSEPT9 exhibited higher sensitivity across all stages in comparison with conventional tumor markers, and 65% of patients with metastases were identified postoperatively through mSEPT9. Tumor recognition after surgery was achieved with the sensitivity of 72% and specificity of 91%. We recommend using mSEPT9 as a non-invasive diagnostic tool for the ongoing monitoring of patients with CRC. The sensitivity and specificity exhibited by mSEPT9 in recognition of tumor after surgery, highlights its particular potential for monitoring of CRC patients.


Comparison of 2 mm single locking miniplates versus 2 mm two non-locking miniplates in symphysis and parasymphysis fracture of mandible.
The purpose of this study is to compare the efficacy of single 2 mm locking miniplates versus two 2 mm non-locking (conventional) miniplates in symphysis and parasymphysis fracture of mandible. This present study included 40 patients of maxillofacial trauma having mandibular symphysis/parasymphysis fractures in which open reduction and internal fixation is indicated. Patients were selected according to the inclusion criteria and divided into two groups, i.e. Group 1: consisted of 20 patients, requiring open reduction and internal fixation with 2 mm two non-locking titanium plate and Group 2: consisted of 20 patients, requiring open reduction and internal fixation with 2.0 mm single ultra-locking titanium plate. Fracture was then stabilized and postoperative clinical examination was carried out on 3rd day, 1st, 2nd, 4th, and 8th week. Results of this study suggested that the use of single 2.0 mm locking miniplate could be a viable option instead of using two miniplates in anterior mandibular fracture as advocated by Champy, as it provides equally good outcome along with placement of lesser implant material. Single locking miniplates give the advantage of equally good stability and early restoration of function with almost similar results as seen in osteosynthesis with two miniplates. It was also found that less precision was required in plate adaptation when using single locking miniplate. This study suggests that there is not much difference in surgical outcome with the use of either single locking miniplate or two conventional miniplates in anterior mandibular region.


Chiral separations of amino acids using di- and tri-peptides for zwitter-ion pair chromatography.
Separations of tryptophan enantiomers by zwitter-ion pair chromatography using small peptides as ion-pairing agents have been studied with emphasis upon the nature of the peptide, the mobile phase composition, and the nature of the chromatographic support. In addition, this procedure has been extended successfully to two other amino acids.


Real-time quantitative RT-PCR detection of disseminated endometrial tumor cells in peripheral blood and lymph nodes using the LightCycler System.
Some endometrial cancer patients without clinical evidence of extrauterine spread die as a result of recurrence even after curative operation. These recurrences may arise from occult tumor cells that are not detected by conventional methods. The goal of this study was to develop a quantitative method for the detection of disseminated tumor cells (DTCs) in the peripheral blood (PB) and lymph nodes (LNs) of patients with endometrial cancer. Ninety-eight PB samples from 30 patients and 218 LNs from 14 patients were studied. Real-time quantitative analysis was performed using a LightCycler instrument and a TaqMan probe for cytokeratin 19 (CK19) as a marker gene. This method resulted in the reproducible quantitation of 10 to 10(6) MCF-7 cells (CK19-expressing breast cancer cell line) per 10(6) peripheral blood nucleated cells. CK19 mRNA expression was detected in 28 PB samples and in 62 LNs. Only three preoperative PB samples and one postoperative PB sample (from four patients) and 33 LNs (from six patients) were PCR-positive. The PCR-positive rate of LNs was higher in patients with pathologically metastatic (path-positive) LNs than in patients with path-negative but PCR-positive LNs. Furthermore, the CK19 mRNA background expression rate was higher in the LNs of path-negative but PCR-positive patients than in LNs of path-negative and PCR-negative patients. Real-time qRT-PCR with TaqMan probes is a sensitive, specific and rapid method for the detection of DTCs in PB and LNs. Additional studies with larger numbers of patients and adequate follow-up would be of benefit.


The HIV-1 capsid protein C-terminal domain in complex with a virus assembly inhibitor.
Immature HIV particles bud from infected cells after assembly at the cytoplasmic side of cellular membranes. This assembly is driven by interactions between Gag polyproteins. Mature particles, each containing a characteristic conical core, are later generated by proteolytic maturation of Gag in the virion. The C-terminal domain of the HIV-1 capsid protein (C-CA) has been shown to contain oligomerization determinants essential for particle assembly. Here we report the 1.7-A-resolution crystal structure of C-CA in complex with a peptide capable of inhibiting immature- and mature-like particle assembly in vitro. The peptide inserts as an amphipathic alpha-helix into a conserved hydrophobic groove of C-CA, resulting in formation of a compact five-helix bundle with altered dimeric interactions. This structure thus reveals the details of an allosteric site in the HIV capsid protein that can be targeted for antiviral therapy.


Correction: MicroRNA-34a expression levels in serum and intratumoral tissue can predict bone metastasis in patients with hepatocellular carcinoma.
[This corrects the article DOI: 10.18632/oncotarget.13531.].


Muscular development in the urinary tract.
The structures of the ureter, ureterovesical junction, bladder and sphincteric urethra were investigated histologically in 17 human fetuses (from 3rd to 21st weeks) and 2 neonates, with particular emphasis on their muscular development. The differentiation of ureteral muscle begins from the upper part of the ureter at the 12th week and muscle bundles run spirally. The purely longitudinal intramural ureteral muscle differentiates much later than the upper ureteral muscle and begins to form muscle bundles at the 17th week. The deep periureteral sheath and the trigonal muscle differentiate at an almost similar pace to the intramural ureteral muscle. The detrusor muscle begins to differentiate from the apical dome of the bladder at the 7th week. Distinct superficial periureteral sheath is also seen around the 12th week. The urethral striated muscle is recognized at the 8th week. It starts to develop in the anterior wall of the urethra as a dense cellular accumulation which eventually extends caudolaterally to form a U-shaped figure. The urethral smooth muscle starts its differentiation between the 9th and 11th weeks inside the urethral striated muscle.


Refractive status and prevalence of myopia among Chinese primary school students.
The aim of this study was to investigate the prevalence of myopia in key (university-oriented) and non-key elementary schools in China using a traditional and a new criterion for myopia diagnosis in an epidemiological study. This school-based, cross-sectional study examined students from four key schools and seven non-key schools. Non-cycloplegic autorefraction and visual acuity (VA) were performed on each student. Myopia was defined as a spherical equivalent (SE) refractive error not better than -1.00 D. A questionnaire was also administered. Of the 13,220 students examined, 6,546 (49.5 per cent) had myopia using the criterion of SE not better than -1.00 D. However, 2,246 (34.3 per cent) of these myopes had VA ≥ 0 logMAR in both eyes, indicating they were not functioning as myopes. Thus, a second myopia criterion was adopted: SE refractive error not better than -1.00 D + uncorrected VA ≥ 0 logMAR in at least one eye. By this definition, only 32.5 per cent of the overall sample had myopia. Students in key schools had a higher prevalence of myopia than those in non-key schools (53.8 per cent versus 44.7 per cent) by the initial criterion. By the new criterion, the prevalence of myopia was 41.2 per cent versus 22.7 per cent. Myopia was equal in grade 1 of both school types, but accelerated faster in key schools, where there was a much higher prevalence of myopia by fourth grade, and continued up to 79.2 per cent prevalence by sixth grade based on SE refractive error not better than -1.00 D. Students in more competitive university-oriented elementary schools developed myopia much faster than those in regular schools, although they started with the same level of myopia. Since one-third of the 'myopes' had VA ≥ 0 logMAR in both eyes, they would not be prescribed a correction, or be clinically treated as myopes. A new criterion of SE refractive error not better than -1.00 D + uncorrected VA ≥ 0 logMAR in at least one eye was tested. This criterion is more clinically appropriate and could be used in future epidemiological studies.


Self-assembling of nanoscopic molecular rectangles, extended helicates and porous-like materials based on macrocyclic dicopper building blocks under fine supramolecular control.
Upon reaction with a dicarboxylate linker, macrocyclic dicopper complexes encode for a selective supramolecular 2 + 2 self-assembly of nanoscopic rectangles, a new class of molecular helicates, and porous-like materials via fine structural control at three supramolecular levels.


A water-soluble membrane transporter for biologically relevant cations.
Synthetic ionophores are promising therapeutic targets, yet poor water solubility limits their potential for translation into the clinic. Here we report a water-soluble, supramolecular self-associating amphiphile that functions as a cation uniporter in synthetic vesicle systems, deriving mechanistic insight through planar bilayer patch clamp experiments.


Effects of light intensity on membrane differentiation in Rhodopseudomonas capsulata.
Cells of Rhodopseudomonas capsulata, strain 37b4, leu-, precultivated anaerobically under low light intensity, were exposed to high light intensity (2000 W.m-2). The cells grew with a mass doubling time of 3 h. The synthesis of bacteriochlorophyll (BChl) began after two doublings of cell mass. Reaction center and light-harvesting BChl I (B-875) were the main constituents of the photosynthetic apparatus incorporated into the membrane. The size of the photosynthetic unit (total BChl/reaction center) decreased and light-harvesting BChl I became the dominating BChl species. Concomitant with the appearance of the different spectral forms of BChl the respective proteins were incorporated into the membrane, i.e. the three reaction center polypeptides, the polypeptide associated with light-harvesting BChl I, the two polypeptides associated with BChl II. A polypeptide of an apparent molecular weight of 45 000 was also incorporated. A lowering of the light intensity to 7 W.m-2 resulted in a lag phase of growth for 6 h. Afterwards, the time for doubling of cell mass was 11 h. The concentration of all three BChl complexes (reaction center, light-harvesting BChl I and II complexes)/cell and per membrane protein increased immediately. Also the size of the photosynthetic unit and the amount of intracytoplasmic membranes/cell increased. The activities of photophosphorylation, succinate dehydrogenase, NADH dehydrogenase and NADH oxidation (respiratory chain)/membrane protein are higher in membrane preparations isolated from cells grown at high light intensities than in such preparations from cells grown at low light intensities.


The safe use of syringe drivers for palliative care: an action research project.
A palliative care team in north Scotland identified serious drug errors occurring in the local health-care trust. These were connected with the use of variable rate syringe drivers (IVAC P100) to deliver pain and symptom management rather than the more suitable Graseby MS26. An action research approach was taken to effecting change. An educational workshop was set up which 23 nurses attended. Clinical support was provided and 3 months later an evaluation was carried out. Of the 13 nurses who had used an MS26, most were able to correctly follow the process of setting up the driver and had made appropriate observations, but drug calculations were a problem. Change was stated to have taken place in seven clinical areas but the degree of change was variable. Facilitators and obstacles to the change process are identified and recommendations made for the next round in the action research cycle.


Validity of a point-of-care based on heterophile antibody detection for the diagnosis of infectious mononucleosis in primary care.
To evaluate the validity of a point-of-care test to diagnose infectious mononucleosis (IM) compared with Epstein-Barr virus (EBV) specific serology. Patients over 14 years with sore throat and four Centor criteria--tonsillar exudate, fever, lymph glands tenderness and absence of cough--and negative pharyngeal testing for group A β-haemolytic streptococcal antigen were consecutively recruited. All patients underwent pharyngotonsillar swab for microbiological culture, the rapid OSOM MonoTest for the diagnosis of IM in whole blood, the Paul-Bunnell test and complete blood analysis with serology for EBV and cytomegalovirus the day after the visit and at 15 days. Sensitivity and specificity were determined. We included 145 patients with a mean age of 24 ± 6.8 years. Of these, serology was determined in 129 subjects, with IM being diagnosed in 14 (10.9%). Both the MonoTest and the Paul-Bunnell test were positive in 13 patients with IM (92.9%) with no patient without disease being positive for either test--sensitivity of 92.9% (95% CI: 64.2-99.6%) and specificity of 100% (95% CI: 96-100%). The culture showed streptococcus A infection in 1 case (0.7%) and streptococcus C in 62 cases (42.8%). A total of 78 patients presented past infection by EBV (60.5%). Only one out of 10 patients with sore throat, four Centor criteria and negative rapid test for streptococcal infection presents IM. Despite the MonoTest presenting optimum sensitivity and specificity, it was found to have the same validity as the Paul-Bunnell test, with serological study continuing to be necessary for precise diagnosis of IM.


Immunity and amyloid beta, total tau and neurofilament light chain: Findings from a community-based cohort study.
We investigated how components of immunity relate to biomarkers of Alzheimer's disease (AD) in plasma and explored the influence of AD genetic risk factors in the population-based Rotterdam Study. In 7397 persons, we calculated the granulocyte-to-lymphocyte ratio (GLR), platelet-to-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). In 3615 of these persons, plasma amyloid-beta (Aβ)42 and Aβ40 were measured. Next, we constructed an overall genetic risk score (GRS) based on genome-wide significant variants, both including and excluding APOE ε4. All innate immunity phenotypes were related to higher Aβ, most strongly with a doubling in GLR leading to a 1.9% higher Aβ42 (95% confidence interval [95% CI] 0.4 to 3.3%) and 3.2% higher Aβ40 (95% CI 2.0 to 4.3%). Higher AD GRS including APOE ε4 was associated with higher immunity markers. Higher levels of immunity markers were associated with higher Aβ in plasma. Participants with a higher genetic predisposition to AD had higher immunity markers, where these effects were mainly driven by APOE ε4.


Evaluation of epidemiologic evidence on the role of nutrition in the development of diabetes and its complications.
This article evaluates the body of epidemiologic evidence on the effects of nutritional factors in diabetes development published within the past 5 years (2000-2004), considering strengths and weaknesses of specific studies, as well as of various study designs in general. Furthermore, this article aims to determine whether clinical practice and public health practice guidelines should, or should not, be determined based on the totality of available scientific evidence.


Involvement of the cholinergic system of CA1 on harmane-induced amnesia in the step-down passive avoidance test.
β-carboline alkaloids such as harmane (HA) are naturally present in the human food chain. They are derived from the plant Peganum harmala and have many cognitive effects. In the present study, effects of the nicotinic system of the dorsal hippocampus (CA1) on HA-induced amnesia and exploratory behaviors were examined. One-trial step-down and hole-board paradigms were used to assess memory retention and exploratory behaviors in adult male mice. Pre-training (15 mg/kg) but not pre-testing intraperitoneal (i.p.) administration of HA decreased memory formation but did not alter exploratory behaviors. Moreover, pre-testing administration of nicotine (0.5 µg/mouse, intra-CA1) decreased memory retrieval, but induced anxiogenic-like behaviors. On the other hand, pre-test intra-CA1 injection of ineffective doses of nicotine (0.1 and 0.25 µg/mouse) fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which did not alter exploratory behaviors. Furthermore, pre-testing administration of mecamylamine (0.5, 1 and 2 µg/mouse, intra-CA1) did not alter memory retrieval but fully reversed HA-induced impairment of memory after pre-training injection of HA (15 mg/kg, i.p.) which had no effect on exploratory behaviors. In conclusion, the present findings suggest the involvement of the nicotinic cholinergic system in the HA-induced impairment of memory formation.


HLA-DM is expressed on the cell surface and colocalizes with HLA-DR and invariant chain in human Langerhans cells.
The subcellular distribution patterns of molecules involved in the process of antigen loading [HLA-DR, HLA-DM, and the cytoplasmic and luminal parts of the invariant chain (Ii, CD74)] were investigated in Langerhans cells (LC), both qualitatively and quantitatively. The analysis was performed by immunofluorescence labelling of acetone-fixed vertical cryostat sections from normal human skin specimens and subsequent examination using confocal laser scanning microscopy (CSLM). The intensity-modulated multiple-wavelength scanning (IMS) technique was used to enhance channel separation when scanning dual-labelled specimens. The mean (n = 9) relative epidermal volumes of reactivity were: HLA-DR 8%+/-3%, HLA-DM 6%+/-2%, luminal Ii 6%+/-2%, and cytoplasmic Ii 4%+/-1%. The difference between HLA-DR and the other epitopes was significant at the P<0.001 level. All molecule combinations, except the combination of HLA-DM and luminal Ii (which was not studied), were to various extents colocalized. Experiments performed on unfixed epidermal sheets showed that HLA-DM is present on the cell surface of LC, suggesting that HLA-DM may interact with HLA-DR on the surface to induce peptide loading.


The neural mechanism of non-phase-locked EEG activity in task switching.
Flexible switching between different tasks is an important cognitive ability for humans and it is often studied using the task-switching paradigm. Although the neural mechanisms of task switching have been extensively explored in previous studies using event-related potentials techniques, the activity and process mechanisms of non-phase-locked electroencephalography (EEG) have rarely been revealed. For this reason, this paper discusses the processing of non-phase-locked EEG oscillations in task switching based on frequency-band delineation. First, the roles of each frequency band in local brain regions were summarized. In particular, during the proactive control process (the cue-stimulus interval), delta, theta, and alpha oscillations played more roles in the switch condition while beta played more roles in repeat task. In the reactive control process (post-target), delta, alpha, and beta are all related to sensorimotor function. Then, utilizing the functional connectivity (FC) method, delta connections in the frontotemporal regions and theta connections located in the parietal-to-occipital sites are involved in the preparatory period before task switching, while alpha connections located in the sensorimotor areas and beta connections located in the frontal-parietal cortex are involved in response inhibition. Finally, cross-frequency coupling (CFC) play an important role in working memory among different band oscillation. The present study shows that in addition to the processing mechanisms specific to each frequency band, there are some shared and interactive neural mechanism in task switching by using different analysis techniques.


Direct-write thermocapillary dewetting of polymer thin films by a laser-induced thermal gradient.
A positive-tone 2D direct-write technique that can achieve sub-wavelength patterning by non-linear overlap effects in a conventional polymer system is described. The technique involves relatively inexpensive free-space optics, skips the usual development step, and promises the possibility of a lithographic method that is solvent-free.


Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.
Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome-wide association study to examine rate of cognitive decline (ROD) in patients with AD. We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes. Suggestive associations (P < 1.0 × 10-6 ) were observed on chromosome 15 in DNA polymerase-γ (rs3176205, P = 1.11 × 10-7 ), chromosome 7 (rs60465337,P = 4.06 × 10-7 ) in contactin-associated protein-2, in RP11-384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10-7 ), family with sequence similarity 214 member-A on chromosome 15 (rs2899492, P = 5.94 × 10-7 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10-7 ) and 4 (rs1304013, P = 7.73 × 10-7 ). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified. Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein (APOE) ε4 and ε2 variants, do not have a major impact.


Micro RNAs mir-106a, mir-122 and mir-197 are increased in severe acute viral hepatitis with coagulopathy.
The severity of acute viral hepatitis, which may be caused by several distinct viruses, varies among individual patients. In rare cases, severe hepatic injury with sudden loss of liver function may occur, which is clinically indicated by the occurrence of coagulopathy or encephalopathy. As the molecular mechanisms of this liver injury are largely unknown, we investigated extracellular micro RNA (miRNA) profiles in 54 patients acutely infected with one of four different hepatotropic viruses, in order to identify those miRNAs which indicate severe viral hepatitis associated with coagulopathy. First, the profile of miRNAs was extensively analysed using a microarray-based approach in highly characterized 24 patients, matched in terms of sex, age and level of liver enzymes, as well as in three healthy controls. The cohort included samples from 18 patients with moderate and six individuals with severe hepatitis, indicated by abnormal prothrombin time and higher alanine aminotransferase and bilirubin levels. miRNAs found to be upregulated in severe hepatitis were then quantified by real-time PCR in the expanded cohort of 54 patients. Comprehensive microarray-based miRNA profiling identified upregulation of mir-106a, mir-122 and mir-197 in patients with severe acute viral hepatitis with coagulopathy, as compared to patients who did not develop coagulopathy. mir-106a, mir-122 and mir-197 were then proven to be significantly upregulated in patients with severe acute viral hepatitis by quantitative real-time PCR (P < 0.01, Mann-Whitney U-test). mir-106a, mir-122 and mir-197 could be potential markers for severe acute viral hepatitis associated with coagulopathy.


Inflammatory sarcomatoid carcinoma of the lung: report of three cases and clinicopathologic comparison with inflammatory pseudotumors in adult patients.
Although the capacity for some pulmonary carcinomas to mimic sarcomas is well recognized, their potential resemblance to selected benign lesions of the lung is currently underappreciated. The authors herein report three examples of sarcomatoid bronchogenic carcinoma with a deceptively bland appearance and an investment of reactive inflammation, such that they resembled pseudotumors histologically. These lesions occurred in two men and one woman who were 44, 61, and 63 years old, respectively, at diagnosis. All patients presented with a productive cough, hemoptysis, or chest pain. Their pulmonary masses were irregularly marginated radiographically, and ranged in size from 2.5 to 5.5 cm. Two were treated with lobectomy, and one underwent a wedge excision, followed by radiotherapy to the thorax. Despite these measures, each patient with inflammatory sarcomatoid carcinoma (ISC) died of disease or is likely to do so. Microscopically, ISCs were composed of uniform spindle cell proliferations with only modest nuclear pleomorphism, limited mitotic activity, and an arrangement in fascicles, storiform configurations, or haphazard arrays. Lymphocytes and plasma cells were interspersed throughout each of them, and keloidal stromal collagen was apparent internally in two examples. Two of the neoplasms also invaded pulmonary blood vessels or bronchi. A comparison group of 10 adults with pulmonary inflammatory pseudotumors (IPs) of the fibrous histiocytoma type shared several clinical attributes with ISC and showed closely similar histological features, except that the IPs lacked mitoses and invasiveness, and contained xanthoma cells or multinucleated elements in some cases in this series. Immunohistochemical analyses showed consistent dissimilarities between ISC and IP; keratin and epithelial membrane antigen were present in ISC but not IP, whereas actin was observed only in the proliferating spindle cells of IP. In summary, the potential clinicopathologic overlap between ISC and IP suggests that caution should be exercised in the separation of these two lesions. In particular, it is unwise to attempt to make this distinction in an intraoperative frozen section setting.


The relationship of infection with Chlamydia trachomatis to the parameters of male fertility and sperm autoimmunity.
The relationship of past exposure to C. trachomatis to the parameters of male fertility was examined in men from infertile couples whose wives had no known female fertility factors. In this population, the frequency of C. trachomatis antibody was low. Past infection with C. trachomatis was associated with a history of nonspecific urethritis, and with the presence of sperm agglutinating antibodies in serum. We found no difference in the seminal fluid analyses, physical examinations, or sperm penetration assays of the men with or without chlamydial antibody.


Complex interaction networks of cytokines after transarterial chemotherapy in patients with hepatocellular carcinoma.
Treating hepatocellular carcinoma with transarterial chemoembolization (TACE) induces both local inflammation in the tumor microenvironment as well as systemic inflammation. We analyzed serum cytokine response to TACE to evaluate this. Serum samples obtained from 203 HCC patients treated with TACE were analyzed for inflammatory cytokines including interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-9, IL-10, IL-12, IL-13, IL-17, IL-22, TNF-α, IFN-γ, and C-reactive protein (CRP) levels. Cytokine concentrations were measured at day 0 (D0, baseline, n = 203), day3 (D3, n = 156), day7 (D7, n = 147), and day 60 (D60, n = 115) after TACE. Network analysis of the cytokines was performed to understand their interactive relationship. After TACE, IL-1β, -6,-9, -12, and -22 increased by D60. IL-2, -5, -10, -17A and INF-γ decreased by D60, and IL-4, -13 and TNF-α revealed stable concentration. D0 network revealed that IL-2, -4, -5, and -10 formed a module. D3 network had the highest clustering coefficient and average degree that revealed similar pattern as CRP. D7 network revealed that IL-6, -9 and CRP were isolated from the network. D60 network had the lower network heterogeneity and lower clustering coefficient, network diameter, shortest path and characteristic path length. Degree correlation revealed that assortative network turned to disassortative network by D60 indicating that the network gained scale free feature. D60 cytokine network retained inflammatory function and these parameters indicated that the systemic inflammation induced by TACE appeared to be attenuated by D60. IL-9 at D3 and D7 seemed to be related to anti-tumor effect and IL-6 at D7 and D60, and IL-22 at D60 was related to regenerative but not pro- or anti- inflammatory function. Median survival month of patient group with high and low values of cytokine with P-values were as follows: D0 CRP, 9.5 and 54.2 months (P<0.0001); D0 IL-2, 39.9 and 56.1 months (P = 0.0084); D3 CRP, 31.3 and 55.1 months (P = 0.0056); D7 CRP, 28.7 and 50.7 months (P = 0.0065), respectively. TACE is associated with systemic inflammation which appears to peak at Day 3 and resolve by D60. Among the tested cytokines, IL-6 and IL-22 appear to play a regenerative role.


Verification of absorbed dose rates in reference beta radiation fields: Measurements with an extrapolation chamber and radiochromic film.
Beta Secondary Standard 2 (BSS 2) provides beta radiation fields with certified values of absorbed dose to tissue and the derived operational radiation protection quantities. As part of the quality assurance, the reliability of the CDTN BSS2 system was verified through measurements in the 90Sr/90Y and 85Kr beta radiation fields. Absorbed dose rates and their angular variation were measured with a 23392 model PTW extrapolation chamber and with Gafchromic radiochromic films on a PMMA slab phantom. The feasibility of using both methods was analyzed.


A New Combined Laparoscopic-Vaginal Lateral Suspension Procedure for the Treatment of Pelvic Organ Prolapse.
To show an original technique of a new combined vaginal-laparoscopic lateral suspension in Hysteropexy with cistocele and rectocele. In recent years, changes in attitudes toward sexuality, psychological value of reproductive organs and the desire to preserve fertility have led to a growing interest in uterine-preserving surgery for Pelvic Organ prolapse. Minimally invasive procedures derived from sacrocolpopexy are considered the gold standard in the treatment of apical Pelvic Organ prolapse. However, dissection at the level of the promontory may be challenging, particularly in obese women and when an anatomical variation exists. This may be associated with rare but serious neurological or ureteral morbidity as well as life-threatening vascular injury. Stepwise demonstration of the technique with narrated video footage. Local institutional review board was consulted, and this study was exempted from approval. Our technique entails 2 times. During the vaginal time, a polypropylene mesh is fixed to the cervical fascia and the 2 extremities are introduced in the abdominal cavity through the Douglas pouch. During the laparoscopic time, a retroperitoneal tunnel is made along the walls of the lateral abdominal walls; thereafter, each of the 2 extremities of the mesh is passed through the omolateral tunnel and "tension-free" suspended to the abdominal wall. Our combined technique may allow a safer approach, reducing the risks of serious complications. Moreover, it leads to a more physiological orientation of the vaginal axis. Further controlled studies are needed to confirm our suggestion.


Lipocalin-2 protects against renal ischemia/reperfusion injury in mice through autophagy activation mediated by HIF1α and NF-κb crosstalk.
Renal ischemia/reperfusion injury is a main cause of acute kidney injury (AKI) triggering an inflammatory response associated with infiltrating macrophages. Lipocalin-2 (Lcn2) levels correlate positively and protect against renal ischemia/reperfusion injury. However, the mechanisms remain unclear. The aim of study was to investigate the protective mechanisms of Lcn2 on renal ischemia/reperfusion injury. We found that Lcn2 deficiency significantly aggravated renal injury as evidenced by higher serum creatinine, more severe morphological injury, and increased tubular epithelial cell death in mice. We also observed that attenuated autophagy in Lcn2-/- mice, as autophagy markers LC3 II level was significantly decreased and p62 was increased in the Lcn2-/- mice after I/R, compared with that of wild type. Mechanistically, we found that recombinant Lcn2 attenuated hypoxia-induced apoptosis in proximal tubule epithelial cells in vitro, and downregulation of HIF-1α blunted Lcn2-induced autophagy and enhanced apoptosis. In addition, the Lcn2 attenuated NF-κb subunit p65 activation under hypoxia conditions. Thus, our findings provide a better understanding of the protective role of Lcn2 in kidney ischemia/reperfusion injury and suggest that Lcn2 may be a promising therapeutic target for treating patients with AKI.


Insulin receptor cycling and insulin action in the rat adipocyte.
The possibility that the insulin receptor of adipocytes undergoes cycling was examined by a method involving pronase digestion at 12 degrees C, followed by insulin binding studies to determine receptor location and quantity. In the absence of insulin treatment, the amount of internal receptors (i.e. protected from pronase) was 10% of total receptor content. Following a 30-min insulin treatment (0.1 microM) at 37 degrees C, the internal receptor content increased 2-fold (206 +/- 12% of control, 100%). This effect was rapid, and maximum internalization was approached by 5 min of insulin treatment. Warming pronase-digested cells to 37 degrees C allowed the internal receptors to move to the cell surface. This movement was rapid also, and expansion of the internal pool by insulin pretreatment provided a 2.4-fold increase in the reinsertion of cell-surface receptors (238 +/- 28% of nontreated cells, 100%). Insulin-pretreated and nontreated cells had approximately 13 and 6%, respectively, of their original cell-surface receptor content, i.e. their content before pronase digestion. These receptors appeared intact after the cycling process, as judged by affinity labeling and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the receptor and its binding subunit. The ability of the recycled receptor to respond to insulin was examined by studies of glucose incorporation into lipids and the inhibition of isoproterenol-stimulated lipolysis. Cells pretreated with insulin and allowed to recycle (e.g. 13% of normal receptor content) were 2-3-fold more responsive and 7-fold more sensitive to subsequent insulin stimulation than nontreated cells (e.g. 6% of normal receptor content), indicating that the recycled receptors are biologically active and coupled to cellular effector systems.


Mode of cell surface marker changes during retinoic acid-induced differentiation in pluripotent embryonal carcinoma cells.
Pluripotent teratocarcinoma cell line, 311, was cultured in the presence of retinoic acid (RA) and studied for the processes of early marker changes associated with cell differentiation. The cell populations that have lost peanut agglutinin (PNA), Lotus tetragonolobus agglutinin (LTA) or wheat germ agglutinin (WGA) receptor increased in proportion to the period since the start of RA treatment. The kinetics of the appearance of these receptor-negative cell populations suggests that the differentiating cells lose lectin receptors in the order of PNA, LTA and WGA. However, the changes in F9 antigen(s) and LTA receptor occurred at an equal frequency in PNA+ and PNA- cells, indicating that, although the loss of lectin receptors takes place in a distinct order, the change in each receptor itself proceeds independently of the state of other lectin receptors.


Quantifying maxillary anterior tooth movement in digital orthodontics: Does the choice of the superimposition software matter?
To compare the agreement between predetermined angular and linear tooth movement measurements processed with three digital model registration software packages. Twenty maxillary intraoral pretreatment scans of patients undergoing clear aligner therapy were randomly selected. Digital setups were generated using OrthoAnalyzer Clear Aligner Studio software to serve as the reference standard. Both pretreatment scans and setups were converted to STL files and exported to Geomagic, OrthoAnalyzer-Model Set Compare, and Compare model registration software packages. The amount of tooth movement of the maxillary incisors and canines was calculated in six degrees of freedom. Statistical significance of the obtained results was expressed at P < 0.01 to account for multiple comparisons. The maxillary central incisors showed the highest agreement for torque and rotation as measured by all software programs. Lateral incisors showed the least agreement in linear movements as measured by Geomagic and Compare, and for tip as measured by Geomagic and OrthoAnalyzer. Maxillary canines had the highest agreement for all linear movements as measured by Geomagic and Compare, and tip as measured by Geomagic and OrthoAnalyzer. Geomagic showed excellent agreement for all measurements except for torque, whereas Compare showed excellent agreement only for rotation and linear measurements. OrthoAnalyzer showed moderate agreement for all measurements except for rotation, which showed good agreement. Maxillary central incisor measurements showed higher agreement compared with measurements of the maxillary lateral incisors and canines. Although none of the software showed poor agreement, Geomagic seemed to have the highest accuracy.


Evaluation of risk factors in developmental dysplasia of the hip in children from multiple pregnancies: results of hip ultrasonography using Graf's method.
The risk factors for developmental dysplasia of the hip (DDH) in infants from unifetal pregnancies are commonly known. Many of these factors also apply to multiple pregnancies. The aim of this paper was to evaluate the influence of selected, widely recognized DDH risk factors in unifetal pregnancy on the development of hip joints in infants from multiple pregnancies. The following risk factors were examined: family history of DDH, breech presentation, duration of pregnancy, birth weight and sex. The study included 200 newborns (400 hip joints) from multiple pregnancies. Ultrasound screening was performed using the Graf method during the first five postnatal days. No cases of hip joint dysplasia requiring treatment were reported in the study group. The analysis of correlations between hip joint type according to Graf and the evaluated risk factors revealed the following results: type IIa hips were reported in 26 (6.91%) infants with a family history of DDH, one infant (1.22%) who demonstrated a breech presentation, 23 prematurely born infants (8.93%) and 28 infants with a mean birth weight of 2402 g. The correlations were not statistically significant. Type IIa hips were reported in 21 female infants (10.82%), which constituted a statistically significant correlation (p < or = 0.05). Among the examined risk factors only the sex of the infant turned out to be significant for the development of hip joints in babies from multiple pregnancies. Type IIa hip joints were more common in female infants.No statistically significant correlations were found between Graf hip types and family history of DDH, breech presentation of the fetus, pregnancy duration under 38 weeks or the infant's birth weight.


Calibration of Phen Green for use as a Cu(I)-selective fluorescent indicator.
Conditional stability constants for the Cu-sensitive fluorescent dye Phen Greentrade mark SK (PGSK) were determined for complexes containing both Cu(I) and Cu(II). Experimental conditions were optimized to minimize oxidation of Cu(I) to Cu(II). A binding constant of 10(11.38) for PGSK and Cu(I) was determined using chloride as the competing ligand and an iterative procedure involving equilibrium calculations to fit experimental data. The new constant was tested by evaluating PGSK fluorescence in the presence of the strong Cu(I)-ligand neocuproine and thiourea. There was good agreement between experimental data and changes in fluorescence predicted by calculations using the new constant and published constants for the competing ligands. Using EDTA to buffer the free ion concentration of Cu2+, the conditional stability constant of PGSK with Cu(II) was measured to be 10(9.8). Both of these new constants are significantly higher than previously published values. Finally PGSK was used to examine the kinetics of Cu(I) dissociation from the biologically important ligand glutathione.


Photochemical formation of perchlorate from aqueous oxychlorine anions.
Evidence of atmospherically produced perchlorate is being accumulated, yet information regarding its formation process is largely unknown. For the first time, the present study demonstrates that perchlorate can be generated as an end-product of photochemical transformation reactions of chlorine precursors such as aqueous salt solutions of hypochlorite, chlorite, and chlorate upon exposure to ultraviolet (UV) radiation. For example, under exposure to UV light from photochemical reactor lamps at a peak wavelength of 253.7 nm for 7 days, the observed perchlorate concentrations were 5, 25, and 626 microg/L at initial chlorite concentrations of 100, 1000, and 10,000 mg/L, respectively. In addition, perchlorate was generated within 7 days from aqueous chlorite solutions at mid-latitude (33 degrees 59'N, 101 degrees 89'W) spring and summer solar radiation. Via UV radiation from the artificial lamps and sunlight, chlorite was converted to chloride (68%) and chlorate (32%) as end-products on the basis of molar percentage. However, perchlorate was not detected from aqueous chloride solutions at initial concentrations up to 10,000 mg/L under the experimental conditions. Relevant mechanistic pathways were proposed based on the fact that chlorine dioxide (as a primary intermediate) may play a significant role in phototransformation of the precursors leading to perchlorate.


20 Years is not long enough.
The author presents some Latin American sociopolitical vicissitudes exemplified by Argentina, where she lives and where she trained and practices as a psychoanalyst. The exposition is based on the impact that her experience with two patients, Ana and Juana, had on her, and is presented in the form of clinical vignettes. The author reflects clinically and technically on the transference and countertransference and on the ways in which self-analysis enabled her to distinguish between the countertransference related to the patient and that related to the psychoanalyst. Finally, the author discusses the traumatic effects of 'the human condition', 'social violence' and 'Evil', referring specifically to the 'repetitive trauma' individuals experience under the globalization of terror and to the use of mechanisms of disavowal that result in serious splitting. The author confronts the reader with totalitarian terror as something that attacks and destroys the main constitutive characteristic of human beings, namely, their ability to think, remarking that H. Arendt is the one who speaks about 'radical evil' as 'the banality of Evil'. The author addresses the question of whether by tempering aggression and organizing levels of symbolization 'words' might prevent the emergence of 'pure jouissance' and be more powerful and significant than violence, overriding it.


"It's like a forgotten issue sometimes …": Qualitative study of individuals living and caring for people with chronic breathlessness.
This study aims to explore the perspectives of patients and carers with chronic breathlessness on current provision of care, care expectations, and self-management needs to develop relevant health services and resources to improve clinical outcomes. In-depth semistructured interviews were conducted on patients living with chronic breathlessness and carers. Thirteen patients (cardiac, respiratory, and noncardiorespiratory) and two carers were interviewed (mean age 57 years, 47% female, median duration with breathlessness 5 years). Four main themes were identified: (1) living with breathlessness, (2) diagnosis delays, misdiagnosis, and knowledge gaps, (3) beyond curing disease: symptom relief and improving quality of life, and (4) self-management and limited support for it. Breathlessness has a high personal impact but remains a neglected condition in Australia. Patients suffer from lack of personal, community, and provider awareness, discontinuity of care, and too few clinical and self-management options.


Simulation of pollutant diffusion in vegetation open channel based on LBM-CA method.
This paper proposes a pollution diffusion model that accurately assesses changes in instantaneous river pollution in vegetation open channels. The model is established based on cellular automata and lattice Boltzmann method (LBM-CA). Flow influence coefficients are incorporated into cellular automata (CA) to represent the effect of vegetation on pollutant diffusion, while the lattice Boltzmann method (LBM) is utilized to simulate flow in vegetation open channels and obtain the flow influence coefficients for each cellular. The results show that the LBM-CA model has high accuracy and that pollutants tend to accumulate in vegetation areas, thereby extending the residence time of pollutants. The model incorporates pollution limits, allowing the prediction of basin pollution levels at specific times. The LBM-CA model provides a method for simulating pollutant diffusion in natural rivers.


Added value of an artificial intelligence algorithm in reducing the number of missed incidental acute pulmonary embolism in routine portal venous phase chest CT.
The purpose of this study was to evaluate the incremental value of artificial intelligence (AI) compared to the diagnostic accuracy of radiologists alone in detecting incidental acute pulmonary embolism (PE) on routine portal venous contrast-enhanced chest computed tomography (CT). CTs of 3089 consecutive patients referred to the radiology department for a routine contrast-enhanced chest CT between 27-5-2020 and 31-12-2020, were retrospectively analysed by a CE-certified and FDA-approved AI algorithm. The diagnostic performance of the AI was compared to the initial report. To determine the reference standard, discordant findings were independently evaluated by two readers. In case of disagreement, another experienced cardiothoracic radiologist with knowledge of the initial report and the AI output adjudicated. The prevalence of acute incidental PE in the reference standard was 2.2% (67 of 3089 patients). In 25 cases, AI detected initially unreported PE. This included three cases concerning central/lobar PE. Sensitivity of the AI algorithm was significantly higher than the outcome of the initial report (respectively 95.5% vs. 62.7%, p < 0.001), whereas specificity was very high for both (respectively 99.6% vs 99.9%, p = 0.012). The AI algorithm only showed a slightly higher amount of false-positive findings (11 vs. 2), resulting in a significantly lower PPV (85.3% vs. 95.5%, p = 0.047). The AI algorithm showed high diagnostic accuracy in diagnosing incidental PE, detecting an additional 25 cases of initially unreported PE, accounting for 37.3% of all positive cases. Radiologist support from AI algorithms in daily practice can prevent missed incidental acute PE on routine chest CT, without a high burden of false-positive cases. • Incidental pulmonary embolism is often missed by radiologists in non-diagnostic scans with suboptimal contrast opacification within the pulmonary trunk. • An artificial intelligence algorithm showed higher sensitivity detecting incidental pulmonary embolism on routine portal venous chest CT compared to the initial report. • Implementation of artificial intelligence support in routine daily practice will reduce the number of missed incidental pulmonary embolism.


N-ethylmaleimide‑sensitive factor siRNA inhibits the release of Weibel-Palade bodies in endothelial cells.
The aim of the present study was to examine the effect of small interfering RNA (siRNA) methods on the expression of N‑ethylmaleimide sensitive factor (NSF) and Weibel‑Palade body (WPB) release in endothelial cells. A small hairpin RNA (shRNA), mediated with an adenovirus vector, was designed to target the N‑terminal functional area of NSF. Subsequently, viruses were transfected into human aortic endothelial cells. The mRNA and protein expression levels of NSF were detected using reverse transcription‑quantitative polymerase chain reaction and Western blot analyses, respectively, and the release of WPBs in the endothelial cells was examined using immunofluorescence. The mRNA expression of NSF in the endothelial cells, which were transfected with the adenoviruses carrying the NSF‑shRNA was significantly decreased, compared with the negative control group (P=0.035) and blank control group (P=0.02). In addition, the mRNA expression of NSF was gradually decreased as duration increased; there were marked differences between the 24, 48 and 72 h groups (P<0.05). The protein expression of NSF was significantly decreased in the experimental group, compared with the negative control group (P=0.004) and blank control group (P=0.031), however, no difference was observed between the negative control and blank control groups (P=0.249). The immunofluorescence staining showed that the release of WPBs in the endothelial cells induced with thrombin was inhibited markedly following transfection with the virus carrying the NSF‑shRNA. Therefore NSF‑siRNA inhibited the mRNA and protein expression levels of NSF, and inhibited the release of WPBs in endothelial cells induced with thrombin. These results suggested that NSF-siRNA may be valuable for preventing and treating atherosclerosis and acute coronary syndrome.


A coding variant in SR-BI (I179N) significantly increases atherosclerosis in mice.
Human coding variants in scavenger receptor class B member 1 (SR-BI; gene name SCARB1) have recently been identified as being associated with plasma levels of HDL cholesterol. However, a link between coding variants and atherosclerosis has not yet been established. In this study we set out to examine the impact of a SR-BI coding variant in vivo. A mouse model with a coding variant in SR-BI (I179N), identified through a mutagenesis screen, was crossed with Ldlr (-/-) mice, and these mice were maintained on a Western-type diet to promote atherosclerosis. Mice showed 56 and 125 % increased atherosclerosis in female and male Ldlr (-/-) Scarb1 (I179N) mice, respectively, when compared to gender-matched Ldlr (-/-) control mice. As expected, HDL cholesteryl ester uptake was impaired in Ldlr (-/-) Scarb1 (I179N) mice compared to Ldlr (-/-) control mice, with a net effect of increased small and very small LDL cholesterol in Ldlr (-/-) Scarb1 (I179N) mice being the most probable cause of the observed increased atherosclerosis. Our data show that non-null coding variants in SR-BI can have a large significant impact on atherosclerosis, even if plasma lipid levels are not dramatically affected, and that human mutations in other candidate lipid genes could significantly impact atherosclerosis.


Health Personnel's Perceived Usefulness of Internet-Based Interventions for Parents of Children Younger Than 5 Years: Cross-Sectional Web-Based Survey Study.
Approximately 10%-15% of children struggle with different socioemotional and psychological difficulties in infancy and early childhood. Thus, health service providers should have access to mental health interventions that can reach more parents than traditional face-to-face interventions. However, despite increasing evidence on the efficacy of internet-based mental health interventions, the pace in transferring such interventions to health care has been slow. One of the major suggested barriers to this may be the health personnel's attitudes to perceived usefulness of internet-based interventions. The purpose of this study was to examine health professionals' perceived usefulness of internet-based mental health interventions and to identify the key areas that they consider new internet-based services to be useful. Between May and September 2018, 2884 leaders and practitioners of infant and child health services were recruited to a cross-sectional web-based survey through the following channels: (1) existing email addresses from the Regional Centre for Child and Adolescent Mental Health, Eastern and Southern Norway, course database, (2) an official mailing list to infant and child health services, (3) social media, or (4) other recruitment channels. Respondents filled in background information and were asked to rate the usefulness of internet-based interventions for 12 different infant and child mental health problem areas based on the broad categories from the Diagnostic Classification of Mental Health and Developmental Disorders of Infancy and Early Childhood (DC:0-5). Perceived usefulness was assessed with 1 global item: "How often do you think internet-based self-help programs can be useful for following infant and child mental health problems in your line of work?" The answers were scored on a 4-point scale ranging from 0 (never) to 3 (often). The participants reported that they sometimes or often perceived internet-based interventions as useful for different infant and child mental health problems (scale of 0-3, all means>1.61). Usefulness of internet-based interventions was rated acceptable for sleep problems (mean 2.22), anxiety (mean 2.09), and social withdrawal and shyness (mean 2.07), whereas internet-based interventions were rated as less useful for psychiatric problems such as obsessive behaviors (mean 1.89), developmental disorders (mean 1.91), or trauma (mean 1.61). Further, there were a few but small differences in perceived usefulness between service leaders and practitioners (all effect sizes<0.32, all P<.02) and small-to-moderate differences among daycare centers, well-baby clinics, municipal child welfare services, and child and adolescent mental health clinics (all effect sizes<0.69, all P<.006). Internet-based interventions for different infant and child mental health problems within services such as daycare centers, well-baby clinics, municipal child welfare services, and child and adolescent mental health clinics are sometimes or often perceived as useful. These encouraging findings can support the continued exploration of internet-based mental health interventions as a way to improve parental support.


Effects of the pharmaceutical formulation of topical medications on corneal epithelial healing after phototherapeutic keratectomy.
To determine the effect of the formulation of topical medications on the healing of corneal epithelial cells after phototherapeutic keratectomy (PTK). Retrospective cohort study. We studied 271 eyes of 189 consecutive patients (aged 67.6 ± 11.8 years) who had undergone PTK for granular corneal dystrophy (n = 140), band keratopathy (n = 47), or lattice corneal dystrophy (n = 2). Postoperatively, generic or brand-named levofloxacin, 0.1% betamethasone, or 0.1% bromfenac sodium hydrate was applied topically. Patients were examined on postoperative days 1, 2, and 5 and weekly thereafter. The time to re-epithelialization was assessed by use of Kaplan-Meier and Cox proportional hazards analyses. The time to re-epithelialization was significantly longer with generic 0.5% levofloxacin, at 8.2 ± 3.5 days, than with 0.5% Cravit (levofloxacin), at 6.7 ± 3.5 days (P = 0.018), or with 1.5% Cravit, at 6.3 ± 2.6 days (P = 0.000). In addition, the time to re-epithelialization was significantly longer with generic 0.1% betamethasone (Sanbetason), at 7.3 ± 3.4 days, than with brand-name 0.1% betamethasone (Rinderon), at 6.1 ± 2.5 days (P = 0.0002). The Cox proportional hazards model indicated that the use of generic formulations for levofloxacin eye drops and 0.1% betamethasone was a significant factor that delayed corneal re-epithelialization (hazard ratio [HR] = 0.72, P = 0.002 and HR = 0.77, P = 0.006, after adjustment for age). Re-epithelialization was significantly shorter in band keratopathy than in corneal dystrophy (HR = 1.56, P = 0.004). No other factors, including age, bandage contact lens, and diabetes mellitus, were significantly associated with time to re-epithelialization. Corneal epithelial healing can be significantly affected by different antibacterial or steroid eye drops. Clinicians need to be aware that a generic formulation may affect corneal epithelial healing.


Salvage of a below knee amputation stump with a free sensate total sole flap preserving continuity of the posterior tibial nerve.
We illustrate the use of a free sole flap with intact posterior tibial nerve in the coverage of a below knee amputation 6 months after an explosive injury to a 12-year-old child. We discuss the indications for lower leg amputation in children, modalities of reconstruction of the amputation stump and possible reason for the observed change of colour of the flap persisting for 14 days.


CD4+CD28null T cells in acute coronary syndrome: lower with ST-elevation myocardial infarction.
We explored any possible difference in the percentage of CD4 + CD28null T cells between patients with ST-segment-elevation myocardial infarction (STEMI) and those with non-ST-segment-elevation acute coronary syndrome. We enrolled 55 consecutive patients admitted with acute coronary syndrome, and 16 healthy control subjects. CD4 + CD28null T cell percentage was assayed by flow cytometry from blood samples withdrawn at the time of enrollment. Mean age was 55.2 ± 10.8 years (69.1% males). Mean CD4 + CD28null T cell percentage was 5.9 ± 3.8% in the study cohort versus 0.8 ± 0.7% in controls (p < 0.001). Mean CD4 + CD28null T cell percentage was higher in patients presenting with non-ST-segment-elevation acute coronary syndrome versus those presenting with STEMI: 7.3 ± 4.1% versus 4.6 ± 3.1%, respectively (p = 0.008). Multivariable regression analysis identified the category of acute coronary syndrome as the only variable independently associated with CD4 + CD28null T cell percentage (p = 0.007). In patients presenting with acute coronary syndrome, the CD4 + CD28null T cell percentage was higher in patients with non-ST-segment-elevation acute coronary syndrome versus those with STEMI. The category of acute coronary syndrome was the only variable independently associated with the CD4 + CD28null T cell percentage in multivariable regression analysis.


Present and Emerging Methodologies in Cryo-EM Single-Particle Analysis.
Over the past decade, technical and methodological improvements in cryogenic electron microscopy (cryo-EM) single-particle analysis have enabled routine high-resolution structural analyses of biological macromolecules, resulting in a flood of new molecular insights into protracted biological questions. However, despite the tremendous progress and success of the field in recent years, opportunities for improvement remain in various aspects of the cryo-EM single-particle analysis workflow (e.g., sample preparation, image acquisition and processing, and structure validation). Here, we review recent advances that have contributed to the principal methods in cryo-EM and identify persisting challenges and bottlenecks that will require further methodological and hardware development.