Emerging applications of phage therapy and fecal virome transplantation for treatment of Clostridioides difficile infection: challenges and perspectives.
Clostridioides difficile, which causes life-threatening diarrheal disease, is considered an urgent threat to healthcare setting worldwide. The current standards of care solely rely on conventional antibiotic treatment, however, there is a risk of promoting recurrent C. difficile infection (rCDI) because of the emergence of antibiotic-resistant strains. Globally, the alarming spread of antibiotic-resistant strains of C. difficile has resulted in a quest for alternative therapeutics. The use of fecal microbiota transplantation (FMT), which involves direct infusion of fecal suspension from a healthy donor into a diseased recipient, has been approved as a highly efficient therapeutic option for patients with rCDI. Bacteriophages or phages are a group of viruses that can infect and destroy bacterial hosts, and are recognized as the dominant viral component of the human gut microbiome. Accumulating data has demonstrated that phages play a vital role in microbial balance of the human gut microbiome. Recently, phage therapy and fecal virome transplantation (FVT) have been introduced as promising alternatives for the treatment of C. difficile -related infections, in particular drug-resistant CDI. Herein, we review the latest updates on C. difficile- specific phages, and phage-mediated treatments, and highlight the current and future prospects of phage therapy in the management of CDI.


Diagnostic value of real-time sonoelastography in congenital muscular torticollis.
The purpose of this study was to evaluate the possible use of real-time sonoelastography in infants with congenital muscular torticollis for predicting treatment outcomes. The study included 20 infants with a sternocleidomastoid muscle thickness of greater than 10 mm, a sonoelastographic score of 4, and involvement of the entire length of the muscle (group 1) and 30 infants with a sternocleidomastoid muscle thickness of less than 10 mm, a sonoelastographic score of 3, and involvement of only part of the muscle (group 2). A physiatrist performed B-mode sonography and sonoelastography together, measured the thickness of the sternocleidomastoid muscle, and calculated the cross-sectional area of the involved muscle in both groups. On color scale sonoelastography, the sonoelastographic score of the sternocleidomastoid muscle was graded from 1 (purple to green: soft) to 4 (red: stiff), and the color histogram of the muscle was subsequently analyzed. The thickness and cross-sectional area of the sternocleidomastoid muscles in group 1 were significantly greater than those in group 2 (P = .001). On the color histograms, the median red pixel values in group 1 were significantly greater than those in group 2 (P = .001). In group 1, the mass in the affected muscle completely disappeared in 16 infants (80%), and a residual mass was detected in 4 (20%) on B-mode sonography at the final outcome. However, in group 2, the mass in the affected sternocleidomastoid muscle completely disappeared in all of the infants. These findings suggest that real-time sonoelastography, although an ancillary technique to conventional sonography, may predict treatment outcomes of congenital muscular torticollis.


Effect of dietary lipids on fatty acid composition of body lipid in rainbow trout (Salmo gairdneri).
Three isocaloric diets were prepared. Diet 1 (Control) contained 22% herring oil. In diets 2 and 3, a third and a half of the herring oil was replaced, respectively, by an animal fat (lard) which contained a high percentage of saturated fatty acids. Each diet was fed to duplicate groups of rainbow trout for 14 wk. The results of the feeding trial indicated that the concentration of the saturated fatty acids in trout body lipid did not increase despite the high concentration of these fatty acids in Diets 2 and 3. Fish growth, feed efficiency, mortality and the level of fatty acids deposited in fish body lipid and phospholipids are discussed.


Endodermal germ cell carcinoma (endodermal sinus tumor) of the vagina in infant girls.
An endodermal sinus tumor (endodermal germ cell carcinoma) was diagnosed in a 1-year-old girl in the vagina after hemorrhage; the tumor was completely removed by radical abdominal surgery. Postoperative polychemotherapy was performed for two years with Actinomycin D, Adriamycin, Vincristin, and Cyclophosphamide. The infant is now tumor-free for 26 months, showing almost normal somatic and psychic development. The characteristic histological patterns and clinical course of this strongly malignant tumor are demonstrated, based on 25 published case reports of endodermal sinus tumors in the vagina of little girls (aged 5-26 months). This neoplasm in early infancy has to be separated from the clear-cell adenocarcinoma of the vagina which occurs after puberty in adolescent girls and young women, and is induced by stilbestrol therapy to the mother during early pregnancy.


A phase 1/2, open-label, parallel group study to evaluate the safety and pharmacokinetics of DARE-HRT1 (80 μg estradiol/4 mg progesterone and 160 μg estradiol/8 mg progesterone intravaginal rings) over 12 weeks in healthy postmenopausal women.
Primary objectives were to evaluate the safety and systemic pharmacokinetics (PK) of DARE-HRT1, an intravaginal ring (IVR), which releases 17β2-Estradiol (E2) with progesterone (P4) for 28 days in healthy postmenopausal women. This was a randomized, open-label, 2-arm, parallel group study in 21 healthy postmenopausal women with an intact uterus. Women were randomized (1:1) to either DARE-HRT1 IVR1 (E2 80 μg/d with P4 4 mg/d) or DARE-HRT1 IVR2 (E2 160 μg/d with P4 8 mg/d). They used the IVR for three 28-day cycles, inserting a new IVR monthly. Safety was measured by treatment emergent adverse events and changes in systemic laboratories and the endometrial bilayer width. Baseline adjusted plasma PK of E2, P4, and estrone (E1) was described. Both DARE-HRT1 IVR were safe. All treatment emergent adverse events were mild or moderate and were distributed similarly among IVR1 versus IVR2 users. Month 3 median maximum plasma ( Cmax ) P4 concentrations were 2.81 and 3.51 ng/mL and Cmax E2 was 42.95 and 77.27 pg/mL for IVR1 and IVR2 groups, respectively. Month 3 median steady state ( Css ) plasma P4 concentrations were 1.19 and 1.89 ng/mL, and Css E2 was 20.73 and 38.16 pg/mL for IVR1 and IVR2 users, respectively. Both DARE-HRT1 IVRs were safe and released E2 in systemic concentrations, which were in the low, normal premenopausal range. Systemic P4 concentrations predict endometrial protection. Data from this study support further development of DARE-HRT1 for the treatment of menopausal symptoms.


The K-pathway revisited: a computational study on cytochrome c oxidase.
Cytochrome c oxidase contains two established proton-conducting structures, the D- and K-pathways. The role of the K-pathway appears to be to conduct the first two protons to be used in water formation, which are taken up on reduction of the oxidized enzyme. Previous computational work has suggested that Lys(I)-319 is neutral over a large pH range and in various redox states. We have constructed oxidase models in different redox states using quantum-chemically derived charge parameters for the redox metal centers. The protonation behaviour of titratable sites in the two-subunit enzyme was defined by continuum electrostatics. The calculations reported here show substantial protonation of Lys(I)-319 at neutral pH once the stable X-ray crystallographic water molecule found immediately next to it is treated explicitly. The immediate structure of the Lys(I)-319 environment is independent of redox state, but the pK(a) value of this residue changes with the redox state of the binuclear heme a3/Cu(B) site whenever that change is electrically uncompensated. Lys(I)-319 is also found to interact electrostatically with the conserved residue Glu(II)-62 in subunit II. These results are discussed in relation to the role of the K-pathway in oxidase function.


The use of fibrin sealant in urology.
Fibrin sealant has been increasingly applied in various surgical fields, including urological surgery, in the last 2 decades. We determined the safety and efficacy of fibrin sealant in urological surgery and identified areas that need further clinical investigation. A MEDLINE search of all available literature regarding the use of fibrin sealant was performed. All articles, including experimental animal studies, prospective and retrospective studies, case series and case reports of fibrin sealant for hemostasis and/or other urological applications, were identified and reviewed. Prospective randomized studies in the field of thoracic and trauma surgery show the efficacy and safety of fibrin sealant for hemostasis. Based on these data fibrin sealant has been used successfully for hemostasis during partial nephrectomy and traumatic renal reconstruction. A number of experimental animal studies, case series and case reports show the efficacy of fibrin sealant for ureteral anastomosis, microsurgical vasal anastomosis, fistula repair, circumcision and orchiopexy as well as it use as an adjunct in other areas of reconstruction. Fibrin sealant is an effective and safe topical agent for controlling surface bleeding during elective and trauma related urological procedures. Using fibrin sealant as an adhesive for reconstruction requires further prospective studies. The introduction of laparoscopic procedures in urology may expand the indications for fibrin sealant as an alternative method of tissue reapproximation. Limiting the routine use of fibrin sealant to procedures with demonstrable benefits is desirable and would lead to a cost saving approach.


Structural requisites of 2-(p-chlorophenoxy)propionic acid analogues for activity on native rat skeletal muscle chloride conductance and on heterologously expressed CLC-1.
(1) The 2-(p-chlorophenoxy)propionic acid (CPP) modulates in a stereoselective manner the macroscopic chloride conductance (gCl), the electrical parameter sustained by the CLC-1 channel, of skeletal muscle. In order to determine the structural requirements for modulating native gCl and to identify high-affinity ligands, the effects of newly synthesised CPP analogues have been evaluated on gCl of rat EDL muscle fibres by means of the two-microelectrode current-clamp technique. (2) Each type of the following independent modification of CPP structure led to a three- to 10-fold decrease or to a complete lack of gCl-blocking activity: replacement of the electron-attractive chlorine atom of the aromatic ring, substitution of the oxygen atom of the phenoxy group, modification at the chiral centre and substitution of the carboxylic function with a phosphonate one. (3) The analogues bearing a second chlorophenoxy group on the asymmetric carbon atom showed a significant gCl-blocking activity. Similar to racemate CPP, the analogue with this group, spaced by an alkyl chain formed by three methylenic groups, blocked gCl by 45% at 100 micro M. (4) These latter derivatives were tested on heterelogously expressed CLC-1 performing inside-out patch-clamp recordings to further define how interaction between drug and channel protein could take place. Depending on the exact chemical nature of modification, these derivatives strongly blocked CLC-1 with K(D) values at -140 mV ranging from about 4 to 180 micro M. (5) In conclusion, we identified four molecular determinants pivotal for the interaction with the binding site on muscle CLC-1 channels: (a) the carboxylic group that confers the optimal acidity and the negative charge; (b) the chlorophenoxy moiety that might interact with a hydrophobic pocket; (c) the chiral centre that allows the proper spatial disposition of the molecule; (d) an additional phenoxy group that remarkably stabilises the binding by interacting with a second hydrophobic pocket.


Genetic contributions to expression of the baboon cingular remnant.
Primitive mammalian molar morphology is characterised in part by a ridge of enamel that encircles the entire base of the molar crown, the cingulum. Many higher primates have reduced the cingulum, but often retain remnant features on the lingual surface of maxillary molars and the labial surface of mandibular molars. Two of these remnants in cercopithecoid primates, the interconulus and interconulid, are morphologically similar though the interconulus is found on maxillary molars and the interconulid is located on mandibular molars. Here we present results from a quantitative genetic analysis of expression of these two traits in a sample of 479 modern savannah baboons from the Southwest Foundation for Biomedical Research (SFBR). We found that both traits are significantly heritable with little variance attributable to other factors, such as sex, age, and molar crown size. Bivariate analyses yielded point estimates for genetic correlations between left and right side expression that are either equal to or not significantly different from 1.0; meaning that 100% of their additive genetic variance is due to the effects of the same gene or suite of genes. By contrast, our estimates of the genetic correlations between maxillary and mandibular expression of this trait range from 0.52 to 0.72, suggesting that 28-52% of the additive genetic variance in the interconulus and interconulid is due to the effects of shared genes. These results demonstrate that intra-arch expression is characterised by complete pleiotropy whereas inter-arch expression is caused by incomplete pleiotropy. These results are relevant to dental developmental studies as well as paleontological analyses of the evolution of the primate dentition.


Multiparametric fully-integrated 18-FDG PET/MRI of advanced gastric cancer for prediction of chemotherapy response: a preliminary study.
To investigate usefulness of multiparametric fully integrated 18-FDG PET/MRI in predicting treatment response after chemotherapy for unresectable advanced gastric cancers (AGCs). Eleven patients with unresectable AGCs underwent multiparametric 18-FDG PET/MRI examinations prior to chemotherapy. Perfusion parameters obtained via dynamic contrast-enhanced MRI, apparent diffusion coefficient values from diffusion-weighted images, and maximum standardized uptake values (SUVmax) from 18-FDG PET were measured. For parameters obtained from 18-FDG PET/MRI data, interobserver agreement was obtained using intraclass correlation coefficients (ICC) and chemotherapy response relationship was evaluated using the Mann-Whitney test and receiver operating characteristic analysis. After chemotherapy, six patients were classified into the responder group and five patients into the non-responder group. For all parameters, moderate to nearly perfect agreement was achieved (ICC = 0.452-0.911). K (trans) values (P = 0.018) and initial area under the curves (iAUCs) (P = 0.045) of gastric cancers were significantly higher in responder group than in non-responder group. The area under the curve was 0.917 for K (trans) and 0.867 for iAUC. However, SUVmax values were not significantly different between the two groups. Multiparametric approach using fully integrated 18-FDG PET/MRI was shown to be feasible for patients with unresectable gastric cancers. In addition, K (trans) and iAUC values can be used as early predictive markers for chemotherapy response. • Multiparametric 18-FDG PET/MRI is feasible for patients with unresectable advanced gastric cancer • K (trans) and iAUC were significantly higher in the responder group of patients • K (trans) , iAUC can be utilized as early predictive markers for chemotherapeutic response.


Distinct financial distress profiles in patients with breast cancer prior to and for 12 months following surgery.
Study purposes were to identify subgroups of patients with breast cancer with distinct self-reported financial distress (FD) profiles and determine which demographic, clinical and symptom characteristics, as well as quality of life (QOL) outcomes were associated with subgroup membership. Patients (n=391) who were assessed for changes in FD a total of 10 times from prior to through 12 months after breast cancer surgery. Latent profile analysis was used to identify subgroups of patients with distinct FD profiles. Three distinct FD profiles (ie, None (14.6%), Low (52.7%), High (32.7%)) were identified. Compared with None and/or Low subgroups, patients in the High subgroup were more likely to report a lower annual household income and performance status; had a higher body mass index, axillary lymph node dissection and more advanced stage disease; had a longer time from cancer diagnosis to surgery; and had received neoadjuvant or adjuvant chemotherapy. In addition, patients in the High subgroup reported higher fatigue, sleep disturbance, state/trait anxiety, depressive symptom scores, and lower attentional function and QOL scores. This study provides new insights on risk factors for and evidence of a higher symptom burden associated with FD. Findings from this study provide clinicians with information on how to identify high-risk patients and to recommend appropriate interventions for both symptom management and FD. Additional research on the mechanisms that underlie the relationships among FD and common physical and psychological symptoms may inform future interventions.


Hodgkin's and Huxley's own assessments of their "quantitative description" of nerve membrane current.
Alan Hodgkin's and Andrew Huxley's mid-20th century work on the ionic currents generating neuron action potentials stands among that century's great scientific achievements. Unsurprisingly, that case has attracted widespread attention from neuroscientists, historians and philosophers of science. In this paper, I do not propose to add any new insights into the vast historical treatment of Hodgkin's and Huxley's scientific discoveries in that much- discussed episode. Instead, I focus on an aspect of it that hasn't received much attention: Hodgkin's and Huxley's own assessments about what their famous "quantitative description" accomplished. The "Hodgkin-Huxley model" is now widely recognized as a foundation of contemporary computational neuroscience. Yet Hodgkin and Huxley expressed serious caveats about their model and what it added to their scientific discoveries, as far back as their (1952d), in which they first presented their model. They were even more critical of its accomplishments in their Nobel Prize addresses a decade later. Most notably, as I argue here, some worries they raised about their quantitative description seem still to be relevant to current work in ongoing computational neuroscience.


Additive manufacturing of bioactive glass biomaterials.
Tissue engineering (TE) and regenerative medicine have held great promises for the repair and regeneration of damaged tissues and organs. Additive manufacturing has recently appeared as a versatile technology in TE strategies that enables the production of objects through layered printing. By applying 3D printing and bioprinting, it is now possible to make tissue-engineered constructs according to desired thickness, shape, and size that resemble the native structure of lost tissues. Up to now, several organic and inorganic materials were used as raw materials for 3D printing; bioactive glasses (BGs) are among the most hopeful substances regarding their excellent properties (e.g., bioactivity and biocompatibility). In addition, the reported studies have confirmed that BG-reinforced constructs can improve osteogenic, angiogenic, and antibacterial activities. This review aims to provide an up-to-date report on the development of BG-containing raw biomaterials that are currently being employed for the fabrication of 3D printed scaffolds used in tissue regeneration applications with a focus on their advantages and remaining challenges.


Pasteurella infection after muraenidae bite in an HIV infected patient.
We report a case of Pasteurella dagmatis wound infection in an immunocompromised HIV infected patient after bite by a marine carnivore in Caribbean Sea (Dominican Republic), presumably a muraenidae. Identification of the Pasteurella species from wound sampling was obtained twice by mass spectrometry and confirmed by 16S RNA sequencing.


Galvanic skin response in photosensitive children.
Investigations of galvanic skin response under stress by different stimuli were carried out in 65 photosensitive and 70 non-photosensitive subjects aged 11--17 years. Photosensitive individuals at the age of 12--15 years showed a more pronounced skin reaction than non-photosensitive ones. The emotional reagibility (expressed by IE = (SEE TEXT), Traxel 1960, Stocksmeier and Langosch 1973) shows significantly higher values than in nonphotosensitive children. In addition to this, photosensitive subjects demonstrate a delayed habituation. Together with further results (Gross-Selbeck et al. 1976) the findings indicate that photosensitivity is not the isolated symptom of a genetically determined increased cerebral excitability, which can represent a factor in the pathogenesis of epilepsy for instance, but must be understood as a special characteristic of a particular constitution.


Glycemia Risk Index as a Novel Metric to Evaluate the Safety of Glycemic Control in Children and Adolescents with Type 1 Diabetes: An Observational, Multicenter, Real-Life Cohort Study.
Glycemia risk index (GRI) is a novel composite metric for the evaluation of the safety of glycemic management and control. The aim of this study was to evaluate GRI and its correlations with continuous glucose monitoring (CGM) metrics by analyzing real-life CGM data in 1067 children/adolescents with type 1 diabetes (T1D) using four different treatment strategies (intermittently scanned CGM [isCGM]-multiple daily injections [MDIs]; real-time CGM-MDIs; rtCGM-insulin pump; hybrid closed-loop [HCL] therapy). GRI was positively correlated with high blood glucose index, low blood glucose index, mean glycemia, its standard deviation, coefficient of variation, and HbA1c. The four treatment strategy groups showed significantly different GRI with the lowest value in the HCL group (30.8) and the highest in the isCGM-MDIs group (68.4). These findings support the use of GRI for the assessment of the glycemic risk and the safety of specific treatment in pediatric subjects with T1D.


Prophages mediate defense against phage infection through diverse mechanisms.
The activity of bacteriophages poses a major threat to bacterial survival. Upon infection, a temperate phage can either kill the host cell or be maintained as a prophage. In this state, the bacteria carrying the prophage is at risk of superinfection, where another phage injects its genetic material and competes for host cell resources. To avoid this, many phages have evolved mechanisms that alter the bacteria and make it resistant to phage superinfection. The mechanisms underlying these phentoypic conversions and the fitness consequences for the host are poorly understood, and systematic studies of superinfection exclusion mechanisms are lacking. In this study, we examined a wide range of Pseudomonas aeruginosa phages and found that they mediate superinfection exclusion through a variety of mechanisms, some of which affected the type IV pilus and O-antigen, and others that functioned inside the cell. The strongest resistance mechanism was a surface modification that we showed is cost-free for the bacterial host in a natural soil environment and in a Caenorhabditis. elegans infection model. This study represents the first systematic approach to address how a population of prophages influences phage resistance and bacterial behavior in P. aeruginosa.


Estimation of peak capacity based on peak simulation.
Peak capacity (PC) is a key concept in chromatographic analysis, nowadays of great importance for characterising complex separations as a criterion to find the most promising conditions. A theoretical expression for PC estimation can be easily deduced in isocratic elution, provided that the column plate count is assumed constant for all analytes. In gradient elution, the complex dependence of peak width with the gradient program implies that an integral equation has to be solved, which is only possible in a limited number of situations. In 2005, Uwe Neue developed a comprehensive theory for the calculation of PC in gradient elution, which is only valid for certain situations: single linear gradients, absence of delays and extra-column effects, Gaussian peaks and constant plate count. Going beyond these limitations implies resolving algebraic expressions that unfortunately cannot be integrated. In this work, PC is predicted for multiple situations based on peak simulation. The approach is more general and can be applied for situations out of the scope of the Neue outline, such as complex multi-linear gradients, including asymmetrical peaks. The plots of PC versus retention time of the last eluted solute give rise to Pareto fronts, and can be useful for the probabilistic enhancement of peak resolution in situations where complex multi-analyte samples are processed.


Pulmonary and cardiac expression of preproendothelin-1 mRNA are increased in heart failure after myocardial infarction in rats. Localization of preproendothelin-1 mRNA and endothelin peptide.
Recent reports indicate that endothelin (ET) plays an important pathophysiological role in congestive heart failure (CHF). However, existing data on local cardiopulmonary ET production are few. No studies have hitherto examined the specific anatomic localization of cardiopulmonary ET synthesis in CHF. Thus, the aims of the present study were to examine whether cardiopulmonary preproET-1 mRNA synthesis is upregulated in CHF and to determine the anatomic localization of preproET-1 mRNA and the mature peptide. CHF was induced in rats by occluding the left coronary artery. Only animals with a left ventricular end-diastolic pressure above 15 mmHg after one week were included (n = 28). Sham-operated animals served as controls (n = 24). Hearts and lungs were examined by mRNA slot blot analyses, in situ hybridization (ISH) and immunohistochemistry (IHC). In CHF-rats, slot blot analyses revealed a 3.5 +/- 1.1-fold and a 6.4 +/- 0.8-fold upregulation of preproET-1 mRNA in the noninfarcted and the infarcted area of the left ventricles, respectively (p < 0.05 for both). ISH revealed that the preproET-1 mRNA was localized predominantly over the granulation tissue in the infarcted region. The ET peptide was predominantly localized to inflammatory cells and remaining cardiomyocytes in the infarcted region as determined by IHC. Lungs from CHF-rats showed a 1.5 +/- 0.1-fold upregulation of preproET-1 mRNA (p = 0.01). The most abundant preproET-1 mRNA and ET-1-like-immunoreactivity (ET-1-ir) was seen over inflammatory cells and over airway epithelial cells. Some ET-1-ir was also located to bronchial and vascular smooth muscle cells. Increased cardiopulmonary ET synthesis strongly suggest a pathophysiological role for ET in CHF.


It doesn't cost anything just to ask, does it? The ethics of questionnaire-based research.
Patient-based outcome measures are increasingly important in health care evaluations, often through the use of paper-based questionnaires. The likely impact of questionnaires upon patients is not often considered and therefore, the balance of benefit and harm not fully explored. Harms that might accrue for research staff are even less frequently considered. This paper describes the use of postal questionnaires within a study of breast disease management in primary care. Questionnaire responses are used to describe the nature of discomfort or harms that may occur in such studies. Ethical issues raised by the harms are discussed in relation to the benefits of the study. Practical suggestions for reducing harm to patients are proposed. A secondary consideration, discomfort to the researcher, is also identified and suggestions made to reduce its effect. Finally, the role of research questionnaires as a study intervention is discussed.


The Irrintzi and Other Folk Cries High Pich and Loud Emission. Can We Learn Something?
In various cultures there are vocal sounds and cries associated with the folk tradition. All these cries are emitted in a single breath, have a high frequency and are loud. They are consequently audible over long distances and cut through other vocal expressions or other sounds generated by instruments. The objective of this work is to acoustically analyze some of these folkloric cries and study elements common to all of them. In this study, Irrintzi, Aturuxo, Tzagrit, ululation Darfur and Kurava cries were subjected to descriptive acoustic spectrographic analysis, and the resulting descriptions were compared both quantitatively, in terms of various acoustic parameters, and qualitatively, in terms of spectrographic characteristics and the way the cries sound. All of the cries contained high frequencies. Spectrograms of the cries revealed that they had a common pattern: a lower initial frequency ascends rapidly (the attack) and is then maintained throughout a stable phase of the emission (the body) before a final drop in frequency (the ending or coda). The body is the longest phase. This initial study of five sounds of folk tradition has opened up a wealth of acoustic and cultural discoveries. Broader studies are now needed to determine if the characteristics we have reported are common to other cries, to look for other similarities, and to delve into meanings, implications and possible applications. In-depth understanding of the mechanism of emission of traditional cries could provide tools for voice re-education in patients with dysphonia due to vocal strain (muscle tension dysphonia, vocal nodules, etc.), for improving voice quality, and for increasing the efficiency of vocal performance.


[An additional unit for the "Minicoma" electroconvulsator].
Discussion of the necessity of unilateral ECT with discontinuous stimulation current and report on an add-on unit to the electroconvulsator "Minicoma" realizing the required stimulation parameters.


Familial lichen planus. Another disease or a distinct people?
When lichen planus strikes families, a very rare happening, it is likely to afflict younger members, to erupt more acutely, extensively, and gravely, attacking also nails and mucous membranes, and to recur. Ten patients with familial lichen planus, two each from five distinct Caucasian families, the parents of whom were unrelated by birth, were found to be carrying HLA-B7 statistically more frequently than in the normal population or in those with the characteristic forms of lichen planus. We hint that their genotype might have rendered them susceptible to a pathogen that precipitated their disease.


From Vanadis to Atropos: vanadium compounds as pharmacological tools in cell death signalling.
Vanadium compounds exert a variety of biological responses, the most notable being their effects as insulin mimetics. More recently, they have been used as pharmacological tools to investigate signalling pathways. Some peroxovanadium compounds act as powerful protein tyrosine phosphatase inhibitors, modulating both the extent and duration of phosphotyrosine signals at the level of the transmembrane growth factor receptors and targets in the cytoplasm and nucleus. A brief history of vanadium compounds, selected chemical properties of vanadium compounds and the ability of peroxovanadium complexes to modulate the activities of protein tyrosine phosphatases and tyrosine kinases are presented in this review by Anne Morinville, Dusica Maysinger and Alan Shaver. From the range of biological activities of these compounds, this review focuses on cytotoxic effects and possible roles of mitogen-activated protein kinases in mediating the effects exerted by vanadium compounds.


Progesterone vaginal ring versus vaginal gel for luteal support with in vitro fertilization: a randomized comparative study.
To compare the efficacy and safety of luteal phase support in IVF with a progesterone (P) vaginal ring or gel (VR or VG). Prospective, randomized, single-blind, multicenter, phase III clinical trial (ClinicalTrials.gov identifier: NCT00615251). Nineteen private and three academic high-volume U.S. IVF centers. One thousand two hundred ninety-seven infertile patients were randomized to a weekly P VR (n = 646) or a daily P 8% VG (n = 651). IVF was performed per site-specific protocols. The day after egg retrieval, patients were randomized and began VR or VG therapy, which continued for up to 10 weeks' gestation. Clinical pregnancy rates at 8 and 12 weeks of pregnancy; rates of biochemical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and cycle cancellation; and safety and tolerability were secondary measures. Clinical pregnancy rates at 8 and 12 weeks were high and comparable between groups: 48.0% for VR and 47.2% for VG at week 8 and 46.4% (VR) and 45.2% (VG) at week 12. Live-birth rates were 45% (VR) and 43% (VG). Adverse event profiles were similar between groups. The weekly P VR provided similar pregnancy rates to the daily VG, with no major differences in safety.


The Need of a Comprehensive Approach in a Condition of Poorly Opioid-Responsive Cancer Pain.
Spinal analgesia is often claimed as an effective strategy for patients with a poor response to systemic opioids. Despite the optimistic data reported in literature with intrathecal drug delivery systems (IDDS) for cancer pain, a critical analysis showed modest benefit. Indeed, intrathecal therapy may be potent means to be used in a very selected population. However, ability to manage spinal therapy combined with the use of opioids and other drugs in the general perspective of a comprehensive palliative care treatment may allow to resolve refractory cancer pain in a patient with a clinical profile of poor pain prognosis, according to the Edmonton staging system. A long-term management of patients who underwent different therapeutic approaches, including multiple opioid lines, intrathecal analgesia, and a comprehensive palliative care treatment, is described. The case reported describes how the management of cancer pain may be complex, requiring a high level of expertise on using opioids, conversion ratios, different routes, particularly the intrathecal one, as well as providing a comprehensive palliative care treatment. No evidence-based treatment can be taken into consideration for such extreme conditions, where only experience and knowledge can guide to an effective course of treatment along a period of about six months. Timely therapeutic strategies are needed to be performed in each challenging clinical situation along the course of disease.


In vitro evaluation of anti-methylglyoxal/glyoxal activity of three phytosterols using glycated bovine serum albumin models.
Reactive intermediate dicarbonyls, such as methylglyoxal (MGO) and glyoxal (GO), have received extensive attention recently due to their high reactivity and capability to form advanced glycation end products (AGEs) in foods, which have been implicated in the progression of age-related complaints. We aimed to investigate the effects of three structurally different phytosterols (PS), including stigmasterol (SS), β-sitosterol (βS), and γ-oryzanol (γO), on AGEs-formation by measuring their anti-GO/MGO activity. The glycoxidation-based products, SDS-PAGE intensity, free lysine, protein thiols, fluorescence microscopy clicks, scavenging of dicarbonyl activity, and protein aggregation in bovine serum albumin (BSA) models were therefore measured. The results showed that PS could strongly inhibit fluorescent-AGEs, lysine residues, intermediate di-carbonyls, beside their disaggregation effects in a dose and structure dependent manner. Additionally, γ-oryzanol strongly inhibited AGEs more than the other PS, mostly due to its distinctive structure. Our results will provide a new foundation for development of different structure of PS as natural AGEs-inhibitors.


Wavelength specific activation of PI 3-kinase by UVB irradiation.
We investigated the effect of UVB irradiation on phospholipid metabolism using normal human diploid skin fibroblasts. When cells were exposed to monochromatic UV light, the intracellular PIP3 level was increased within 1 min in a wavelength-specific manner. The increase was most marked in the UVB range and was inhibited by a PI 3-kinase inhibitor, tyrosine kinase inhibitor, or antioxidant reagents. Furthermore, the decrease of cell viability induced by UVB irradiation was significantly blocked by wortmannin. These results suggest that PI 3-kinase activation is involved in novel cellular responses specific for UVB that lead to cell death.


Bacteriology and therapy of lung abscess in children.
The bacteriology and clinical findings of ten pediatric patients with lung abscess are presented. Bacteriologic data were based on percutaneous transtracheal aspiration obtained before initiation of antimicrobial therapy. Anaerobic bacteria were present in all ten patients; in nine they were mixed with aerobic bacteria. The most frequent isolates were Peptostreptococcus (8), Peptococcus (5), Bacteroides melaninogenicus (6), and Bacteroides fragilis (3). The aerobic isolates most frequently recovered were alpha-hemolytic streptococci (5), group A beta-hemolytic streptococci (4), and Escherichia coli and Klebsiella pneumoniae (4 each). Virtually all abscesses were located in dependent pulmonary segments. Antimicrobial therapy was guided by the bacteriologic findings and was successful in all instances.


Carotid artery intervention.
Atherosclerotic carotid artery disease is a major contributor to the incidence of stroke, particularly in the elderly. Atherosclerosis is a systemic illness and patients often present with multisystem involvement of several vascular beds including coronary, cerebral, and peripheral vascular territories. The majority of strokes related to carotid artery disease are embolic in nature, not occlusive. Non-invasive screening tests including ultrasound, CT angiography and MR angiography are helpful in identifying pathology. However, the gold standard, for diagnosis and treatment allocation remains invasive angiography. Medical therapy to reduce the risk of stroke includes antiplatelet agents, primarily aspirin in doses of 81 mg to 325 mg per day. Control of blood pressure and the use of statin therapy is effective in reducing the incidence of stroke. Carotid endarterectomy is more effective for preventing stroke in symptomatic (transient ischemic attack or stroke) patients with = or >50% diameter stenosis and asymptomatic patients with = or >60% diameter stenosis, than aspirin therapy. In patients at increased risk for surgical complications during stroke prevention surgery (carotid endarterectomy), carotid stents have been shown to be as good or better than surgery at improving outcomes.


Adsorption characteristics of brilliant green dye on kaolin.
Experimental investigations were carried out to adsorb toxic brilliant green dye from aqueous medium using kaolin as an adsorbent. Characterization of kaolin is done by measuring: (i) particle size distribution using particle size analyzer, (ii) BET surface area using BET surface analyzer, and (iii) structural analysis using X-ray diffractometer. The effects of initial dye concentration, contact time, kaolin dose, stirring speed, pH and temperature were studied for the adsorption of brilliant green in batch mode. Adsorption experiments indicate that the extent of adsorption is strongly dependent on pH of solution. Free energy of adsorption (DeltaG0), enthalpy (DeltaH0) and entropy (DeltaS0) changes are calculated to know the nature of adsorption. The calculated values of DeltaG0 at 299K and 323K indicate that the adsorption process is spontaneous. The estimated values of DeltaH0 and DeltaS0 both show the negative sign, which indicate that the adsorption process is exothermic and the dye molecules are organized on the kaolin surface in less randomly fashion than in solution. The adsorption kinetic has been described by first-order, pseudo-second-order and intra-particle-diffusion models. It was observed that the rate of dye adsorption follows pseudo-second-order model for the dye concentration range studied in the present case. Standard adsorption isotherms were used to fit the experimental equilibrium data. It was found that the adsorption of brilliant green on kaolin follows the Langmuir adsorption isotherm.


Spectral decomposition of cerebrovascular and cardiovascular interactions in patients prone to postural syncope and healthy controls.
We present a framework for the linear parametric analysis of pairwise interactions in bivariate time series in the time and frequency domains, which allows the evaluation of total, causal and instantaneous interactions and connects time- and frequency-domain measures. The framework is applied to physiological time series to investigate the cerebrovascular regulation from the variability of mean cerebral blood flow velocity (CBFV) and mean arterial pressure (MAP), and the cardiovascular regulation from the variability of heart period (HP) and systolic arterial pressure (SAP). We analyze time series acquired at rest and during the early and late phase of head-up tilt in subjects developing orthostatic syncope in response to prolonged postural stress, and in healthy controls. The spectral measures of total, causal and instantaneous coupling between HP and SAP, and between MAP and CBFV, are averaged in the low-frequency band of the spectrum to focus on specific rhythms, and over all frequencies to get time-domain measures. The analysis of cardiovascular interactions indicates that postural stress induces baroreflex involvement, and its prolongation induces baroreflex dysregulation in syncope subjects. The analysis of cerebrovascular interactions indicates that the postural stress enhances the total coupling between MAP and CBFV, and challenges cerebral autoregulation in syncope subjects, while the strong sympathetic activation elicited by prolonged postural stress in healthy controls may determine an increased coupling from CBFV to MAP during late tilt. These results document that the combination of time-domain and spectral measures allows us to obtain an integrated view of cardiovascular and cerebrovascular regulation in healthy and diseased subjects.


Design of one-dimensional power spectrum using two-dimensional fast Fourier transform for discrimination of paper-based kraft tapes.
A novel type of spectrum, the one-dimensional power spectrum (1D-PS), was designed for the discrimination of adhesive packing tapes, i.e., kraft tapes. The 1D-PS offered complementary information to that provided by the improved two-dimensional PS (2D-PS), which was calculated using our previously established image processes combined with a two-dimensional fast Fourier transform (2D-FFT) to obtain information about the spatial periodicity within kraft tapes. The 1D-PS was calculated using a three-step image process: (i) the 2D-FFT was applied to 50 randomly selected areas in a transmitted light image; (ii) the obtained 2D-PSs were accumulated without applying a logarithmic transform; (iii) the wavenumber and the maximum intensity were plotted on the x-axis and y-axis, respectively. Through an intra-roll comparison, the 1D-PSs collected from single rolls showed similar profiles. In an inter-roll comparison, the 1D-PSs from 50 commercially available brand-name products were classified into 29 groups. The 1D-PSs contained other useful information than that provided by the improved 2D-PSs: they presented more peaks and absolute intensity with a wider range. The 1D-PSs enabled us to compare the spectra quickly and easily, owing to their unchanging profiles regardless of the orientation of the scanned images. A combined use of the 1D-PSs with the improved 2D-PSs-both spectrum types being convenient, rapid, non-destructive, and applicable to dirty and/or damaged samples-could further improve the identification of kraft tapes.


Exploring the microscopic changes of lipid droplets and mitochondria in alcoholic liver disease via fluorescent probes with high polarity specificity.
Alcoholic liver disease (ALD) has received extensive attention because of the increasing alcohol consumption globally as well as its high morbidity. It is reported that absorbed alcohol can cause lipid metabolism disorder and mitochondria dysfunction, so here in this work, we planned to study the microscopic changes of the two organelles, lipid droplets (LDs) and mitochondria in hepatocyte, under the stimulation of alcohol, hoping to present some meaningful information for the theranostics of ALD by the technique of fluorescence imaging. Guided by theoretical calculation, two fluorescent probes, named CBu and CBuT, were rationally designed. Although constructed by the same chromophore scaffold, they stained different organelles efficiently and emitted distinctively. CBu with high lipophilicity, ascribed to the two butyl groups, can selectively localize in LDs with green fluorescence, while CBuT bearing a triphenylphosphine unit can specifically target mitochondria due to electrostatic interactions with near-infrared (NIR) fluorescence. Both probes displayed remarkable selectivity and sensitivity to polarity, free from the environmental interferences including viscosity, pH and other bio-species. With these two probes, the accumulation of LDs and polarity decrease in mitochondria were clearly monitored at the green and red channels, respectively, in the ALD cell model. CBuT was further applied to image the mice with ALD in vivo. In short, we have confirmed the valuable organelles, LDs and mitochondria, for ALD study and provided two potent molecular tools to visualize their changes through fluorescence imaging, which would be favorable for the further development of theranostics for ALD.


Limbal epithelial stem cell sheets from young donors have better regenerative potential.
To investigate the stemness of limbal epithelial stem cell sheets in relation to the donor's age. Human limbal explants from cadaveric donors were set on human amniotic membrane scaffolds with the xeno-free medium. We evaluated limbal epithelial sheet size, expression of stem/progenitor cell markers, and colony formation efficiency from donors of different age groups (age ≤ 45, age 45-65, and age > 65). Expression of the proliferation marker Ki67, stem/progenitor cell markers p63α and ABCG2, cornea specific marker PANCK, and differentiation marker CK12 were evaluated. To determine the effect of donor age on the storage period of limbal explant sheets, the limbal explant outgrowth sheets were stored in 4 °C for 2 days and analyzed for JC-1, p63α, and PANCK with FACS on each day. From days 6 to 12, the outgrowth area of the limbal epithelial stem cell sheet was significantly larger in the age ≤ 45 groups (296 ± 54.7 mm2, day 9) compared to the other two age groups [age 45-65 group (278 ± 62.6 mm2), age > 65 group (257 ± 44.0 mm2), day 9] (p < 0.01). In terms of stemness, outgrowth cells from aged donors (age > 65) showed lower expression of stem/progenitor cell markers p63α and ABCG2 and decreased CFE compared to the other two groups. There were significantly more p63α+ cells in outgrowth cells in the age ≤ 45 group (18.2 ± 3.6%) compared to the age > 65 group (14.1 ± 4.6%; p < 0.01). Limbal explant outgrowth sheet on the age ≤ 45 group (32.7 ± 7.5%) had higher percentages of cells resisting staining by JC-1 compared with sheets under the age > 65 groups (25.7 ± 7.1%, p < 0.01) (JC-1low). Cells from the age ≤ 45 group showed a higher clonogenic capacity than those from the other two age groups (45 < Age ≤ 65 CFE ratio = 0.7 ± 0.16, p < 0.01; 65 < Age CFE ratio = 0.3 ± 0.06, p < 0.01, vs. Age ≤ 45). In the age > 65 group, positive cells of p63α on D0, 1, and 2 were significantly lower compared to those in the age ≤ 45 group on the storage period (p < 0.01, respectively). Our results imply that donors younger than 65 years of age are a better source of limbal epithelial stem cell sheet generation with high regeneration potential.


Tumour or infection? Misleading spinal radiographs.
Radiological appearances alone are often insufficient to make a precise diagnosis of spinal pathology, and should be supplemented by appropriate investigations, which ideally should include histological and bacteriological examination of the diseased tissues.


Bioluminescent kinase strips: A novel approach to targeted and flexible kinase inhibitor profiling.
In addition to target efficacy, drug safety is a major requirement during the drug discovery process and is influenced by target specificity. Therefore, it is imperative that every new drug candidate be profiled against various liability panels that include protein kinases. Here, an effective methodology to streamline kinase inhibitor profiling is described. An accessible standardized profiling system for 112 protein kinases covering all branches of the kinome was developed. This approach consists of creating different sets of kinases and their corresponding substrates in multi-tube strips. The kinase stocks are pre-standardized for optimal kinase activity and used for inhibitor profiling using a bioluminescent ADP detection assay. We show that these strips can routinely generate inhibitor selectivity profiles for small or broad kinase family panels. Lipid kinases were also assembled in strip format and profiled together with protein kinases. We identified two specific PI3K inhibitors that have off-target effects on CK2 that were not reported before and would have been missed if compounds were not profiled against lipid and protein kinases simultaneously. To validate the accuracy of the data generated by this method, we confirmed that the inhibition potencies observed are consistent with published values produced by more complex technologies such as radioactivity assays.


Efficient adsorption of Pb(II) by sodium dodecyl benzene sulfonate intercalated calcium aluminum hydrotalcites: kinetic, isotherm, and mechanisms.
Two novel adsorbents of CaAl-LDHs and sodium dodecyl benzene sulfonate (SDBS) intercalated CaAl-LDHs (SDBS-CaAl-LDHs) were successfully prepared by co-precipitation. The main composition and physical properties of two samples were characterized by XRD, XPS, FT-IR, TG, and SEM. Batch adsorption experiments were conducted to study the effect of pH, adsorption time, and initial concentration of Pb2+. The results showed that the prime adsorption conditions obtained were pH of 5.2 after 60 min with the initial concentration of 300 mg g-1 for CaAl-LDHs and 350 mg g-1 for SDBS-CaAl-LDHs. At 303 K, the adsorption capacities and removal rates of CaAl-LDHs and SDBS-CaAl-LDHs were found to be 456.05 mg g-1, 91.21% and 682.26 mg g-1, 97.47%, respectively. For CaAl-LDHs, the kinetic data for Pb2+ was best fitted with pseudo-2nd-order model, and the adsorption isotherms followed Langmuir and Freundlich isotherm model. The adsorption data of SDBS-CaAl-LDHs can be best described by the pseudo-second-order kinetic and Langmuir model. The Pb2+ adsorption mechanism on SDBS-CaAl-LDHs was explored by XRD, XPS, and SEM, and the important roles of the electrostatic attraction, precipitation, complexation, and ion exchange were demonstrated. The Langmuir adsorption capacities for SDBS-CaAl-LDHs were 797.63, 828.76, and 854.29 mg g-1 at 293 k, 303 k, and 313 k, respectively. Thus, SDBS-CaAl-LDHs may be a highly economical adsorbent for the treatment of contaminated water.


Acculturation and smoking in North Americans of Chinese ancestry: A systematic review.
Many North American immigrants come from China. Given the critical impact of tobacco use on health, it is important to understand rates and correlates of smoking in this population. This systematic review addressed the question: based on current research, what is the association between acculturation and smoking behaviours in Chinese immigrants to North America? The search was conducted in PubMed, Medline, Web of Science, and Academic Search Complete for papers published from 2005 to 2014. Data were extracted from Canadian and American studies for population characteristics, study design, measures of smoking and acculturation, and findings regarding smoking rates and associations between smoking and acculturation. The literature search identified 147 articles, and 14 met inclusion criteria. Three studies were based on Canadian samples and the remaining 11 were from the United States. Of the 14 papers, 3 reported findings for youth and 11 for adults. Among adults, daily smoking rates were consistently much higher in men than women; for men, rates varied from 9% to 30%. Language use and time in North America were the most common indicators of acculturation. Almost all studies found a relationship between acculturation and smoking, such that more acculturated men smoke less and more acculturated women smoke more. The findings suggest that the association between acculturation and smoking is gender-specific. This correlation is found in youth and adults and in both Canada and the US. Increased acculturation has a protective effect on smoking for Chinese North American men, but a harmful effect for women. Tobacco control interventions need to develop targeted strategies appropriate to these different populations.


A cleavable biotin tagging reagent that enables the enrichment and identification of carbonylation sites in proteins.
The utility of a new, cleavable tag for identifying and enriching protein carbonyls is examined. Using a model system, human serum albumin modified with acrolein, the EZ-Link alkoxyamine-PEG4-SS-PEG4-biotin affinity tag, was tested for its ability to label protein carbonyls in proteomic analyses of protein carbonylation. The efficiency of the labeling was assayed and compared to standard biotin hydrazide reagents. The label was also tested in liquid chromatography-tandem mass spectrometry (LC/MS/MS) experiments. The quality of the fragmentation spectra was assessed and the relative detection efficiency of various modification sites was compared to standard biotin hydrazide reagents. Finally, the viability of using the label with streptavidin bead enrichment protocols in a standard proteomics workflow was probed.


Relationship of plasma cholesterol level to doses of branch-chain amino acids in sepsis.
Plasma cholesterol levels, plasma lactate, and total body RQ were measured in septic patients undergoing total parenteral nutrition (TPN) with glucose, fat, and two different branch-chain amino acid admixtures (49% BCAA and 16% BCAA). Mean plasma cholesterol for all measurements (2.61 +/- 0.94 [SD] mmol/L) was lower than normal; however, it was higher with 49% BCAA than with 16% BCAA (2.94 +/- 0.95 vs. 2.27 +/- 0.81 mmol/L, p less than .001) for comparable loads of glucose, fat, and total amino acids. Plasma lactate and RQ were lower with 49% BCAA than with 16% BCAA (p less than .001 for both). Cholesterol was directly related to the absolute dose of BCAA (p less than .001), was unrelated to the dose of non-BCAA, and was inversely related to lactate (p less than .001). These results suggest that BCAA ketoacids contribute to cholesterol synthesis in sepsis, as well as being an oxidative source. The data also suggest that the reduction in alanine in BCAA-enriched amino-acid TPN assists in the lowering of plasma lactate secondary to abnormal septic glucose metabolism.


Patient-Specific iPSC Model of a Genetic Vascular Dementia Syndrome Reveals Failure of Mural Cells to Stabilize Capillary Structures.
CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) is the most common form of genetic stroke and vascular dementia syndrome resulting from mutations in NOTCH3. To elucidate molecular mechanisms of the condition and identify drug targets, we established a patient-specific induced pluripotent stem cell (iPSC) model and demonstrated for the first time a failure of the patient iPSC-derived vascular mural cells (iPSC-MCs) in engaging and stabilizing endothelial capillary structures. The patient iPSC-MCs had reduced platelet-derived growth factor receptor β, decreased secretion of the angiogenic factor vascular endothelial growth factor (VEGF), were highly susceptible to apoptotic insults, and could induce apoptosis of adjacent endothelial cells. Supplementation of VEGF significantly rescued the capillary destabilization. Small interfering RNA knockdown of NOTCH3 in iPSC-MCs revealed a gain-of-function mechanism for the mutant NOTCH3. These disease mechanisms likely delay brain repair after stroke in CADASIL, contributing to the brain hypoperfusion and dementia in this condition, and will help to identify potential drug targets.


Gas chromatography analysis of serum cholesterol synthesis and absorption markers used to predict the efficacy of simvastatin in patients with coronary heart disease.
We investigated the changes in cholesterol absorption and synthesis markers before and after simvastatin therapy in Chinese patients with coronary heart disease. We developed a gas chromatography method to identify cholesterol synthesis and absorption markers and measured them in patients with coronary heart disease. We then tested their use in predicting the efficacy of simvastatin in lowering cholesterol. Serum samples from 45 patients and 38 healthy humans (controls) were analyzed in a gas chromatography-flame ionization detector. Squalene and five non-cholesterol sterols--desmosterol and lathosterol (synthesis markers) and campesterol, stigmasterol, and sitosterol (absorption markers)--were detected. The recovery rates of the markers were 95-102%. After simvastatin treatment for four weeks, the total cholesterol and low-density lipoprotein cholesterol levels had significantly decreased from the baseline values (p<0.05). The baseline lathosterol level was significantly higher in good responders than in poor responders (p<0.05), and the stigmasterol level was significantly lower in good responders than in poor responders (p<0.05). This method should be suitable for the detection of serum squalene and non-cholesterol markers and can be used to predict the efficacy of simvastatin in patients with coronary heart disease.


The low-density lipoprotein receptor-related protein-1 associates transiently with lipid rafts.
The low-density lipoprotein receptor-related protein-1 (LRP-1) is a multifunctional receptor that undergoes constitutive endocytosis and recycling. To identify LRP-1 in lipid rafts, we biotin-labeled cells using a membrane-impermeable reagent and prepared Triton X-100 fractions. Raft-associated proteins were identified in streptavidin affinity-precipitates of the Triton X-100-insoluble fraction. PDGF beta-receptor was identified exclusively in lipid rafts, whereas transferrin receptor was excluded. LRP-1 distributed partially into rafts in murine embryonic fibroblasts (MEFs) and HT 1080 cells, but not in smooth muscle cells and CHO cells. LRP-1 partitioning into rafts was not altered by ligands, including alpha2-macroglobulin, platelet-derived growth factor-BB, and receptor-associated protein (RAP). To examine LRP-1 trafficking between membrane microdomains, we developed a novel method based on biotinylation and detergent fractionation. Association of LRP-1 with rafts was transient; by 15 min, nearly all of the LRP-1 that was initially raft-associated exited this compartment. LRP-1 in the Triton X-100-soluble fraction, which excludes lipid rafts, demonstrated complex kinetics, with phases reflecting import from rafts, endocytosis, and recycling. Potassium depletion blocked LRP-1 endocytosis but did not inhibit trafficking of LRP-1 from rafts into detergent-soluble microdomains. Our data support a model in which LRP-1 transiently associates with rafts but does not form a stable pool. Fluid movement of LRP-1 between microdomains may facilitate its function in promoting the endocytosis of other plasma membrane proteins, such as the urokinase receptor, which localizes in lipid rafts.


Predictive biomarkers for the efficacy of nivolumab as ≥ 3rd-line therapy in patients with advanced gastric cancer: a subset analysis of ATTRACTION-2 phase III trial.
The phase 3 ATTRACTION-2 study demonstrated that nivolumab monotherapy improved survival compared to placebo in patients with pretreated advanced gastric cancer (AGC). However, the efficacy of nivolumab seems to be limited to a subset of patients. The predictive values of blood neutrophil-lymphocyte ratio (NLR), serum Na, PD-L1 expression, MSI status, tumor EBV infection, and tumor mutation burden (TMB) were investigated in patients with AGC refractory to ≥2 lines of chemotherapy enrolled from Asan Medical Center in ATTRACTION-2 study. All 45 patients were analyzed; nivolumab (n = 28) and placebo (n = 17) groups. The objective response rate, median progression-free survival (PFS), and overall survival (OS) were 16.7%, 1.6 months, and 8.1 months in nivolumab group and 0%, 1.6 months and 6.5 months in placebo group. When comparing nivolumab with the placebo group, tumor PD-L1 expression, blood NLR, and serum Na were significant predictive factors of PFS and OS. A multivariate analysis revealed that PD-L1 ( +) and low NLR (≤ 2.9, median) were associated with better PFS. In the nivolumab group, PD-L1 ( +), low NLR, and normal Na (≥ 135 mmol/L) were associated with higher response and disease control rates, while tumor EBV infection and TMB were not. Tumor PD-L1 expression, blood NLR, and serum Na could be predictive biomarkers for the efficacy of nivolumab in previously treated cases of AGC.


Ionized hypocalcemia after fresh frozen plasma administration to thermally injured children: effects of infusion rate, duration, and treatment with calcium chloride.
A number of cardiac arrests and severe hypotensive episodes have been witnessed associated with the intravenous infusion of fresh frozen plasma (FFP). To clarify the possible role of hypocalcemia, 28 thermally injured anesthetized pediatric patients with massive blood loss were studied to examine the cardiovascular responses (mean arterial pressure [MAP], heart rate, ECG) to 49 infusions of FFP. Rapid, statistically significant reductions in ionized calcium ([Ca2+]) followed each of four rates (1.0, 1.5, 2.0, and 2.5 ml.kg-1.min-1 for 5 minutes) of FFP infusion (P less than 0.0001). The slowest rate resulted in significantly less reduction in [Ca2+] than did the higher infusion rates (P less than 0.002). In five children MAP decreased greater than or equal to 20% below baseline levels, but this was not correlated with rate of FFP administration or decrease in [Ca2+]. The decreases in [Ca2+] and MAP were inversely related to age and unrelated to anesthetic technique. Changes in the Q-oTc interval were not related to [Ca2+]. Adverse cardiovascular responses and reduced [Ca2+] were not significantly different between 5- and 10-minute FFP infusions. Fewer fluctuations in MAP occurred when calcium chloride (CaCl2) was administered; the least fluctuation in [Ca2+] occurred when CaCl2 was administered during the plasma infusion. It is concluded that in thermally injured children 1-17 years old: 1) Rapid infusions of FFP produce sudden but evanescent decreases in [Ca2+]; more rapid infusions result in greater reductions in [Ca2+]. 2) There is no correlation between [Ca2+] and systemic hypotension. 3) Clinically important decreases in MAP occasionally accompany the rapid infusion of FFP.(ABSTRACT TRUNCATED AT 250 WORDS)


Pitfalls of mitral regurgitation assessment in the presence of mitral valve prolapse.
Adequate grading of mitral regurgitation (MR) in patients with mitral valve prolapse (MVP) in the presence of mid-late systolic jets can represent a major challenge. In this entity, jets are commonly overestimated by echocardiography. Correct quantification is crucial and highly relevant for the further management and prognosis of these oftentimes young patients. This case points out potential pitfalls and underlines the importance to systematically include qualitative, quantitative, and semi-quantitative parameters into the echocardiographic assessment.


The radiography of foreign bodies in the eye as carried out at the Birmingham and Midland Eye Hospital.
An account is given of the following procedures at the Birmingham and Midland Eye Hospital; (a) to show if a foreign body is present in the area of the eye; (b) to demonstrate its possible presence within the globe of the eye; (c) to localise its exact position within the globe, using the limbal ring technique.


Investigating the Effect of Implementing a Web-Based Educational Program on Fathers' Involvement in Infant Care 0 to 6 Months.
Fathers need education to understand their role in infant care and its implications regarding the child's health. Virtual education has been able to compensate for the shortcomings of traditional training and education, and with respect to this, the present study was conducted to determine the effect of virtual education on fathers about infant care and their involvement in infant care. The quasi-experimental study was performed on 83 participants in healthcare centers affiliated with North Khorasan University of Medical Sciences. The involvement of fathers in infant care was assessed with a questionnaire of the father's involvement in the care of the infant (mother-reported) in 4-time points: 3-5 days, and 2, 4, and 6 months after birth. Educational materials based on the child's growth and needs and as well as the latest references and national guidelines were prepared, and as the infant grew, were taught step by step to fathers using Soroush's messenger while their questions were answered. The mean score of total father involvement in infant care at two, four, and six months after childbirth was significantly higher in the intervention group than in the control group (p < 0.001). With regard to the lack of access to fathers during their working hours, virtual education can be used to increase their involvement in infant care.


Trusting the hand that feeds: microbes evolve to anticipate a serial transfer protocol as individuals or collectives.
Experimental evolution of microbes often involves a serial transfer protocol, where microbes are repeatedly diluted by transfer to a fresh medium, starting a new growth cycle. This has revealed that evolution can be remarkably reproducible, where microbes show parallel adaptations both on the level of the phenotype as well as the genotype. However, these studies also reveal a strong potential for divergent evolution, leading to diversity both between and within replicate populations. We here study how in silico evolved Virtual Microbe "wild types" (WTs) adapt to a serial transfer protocol to investigate generic evolutionary adaptations, and how these adaptations can be manifested by a variety of different mechanisms. We show that all WTs evolve to anticipate the regularity of the serial transfer protocol by adopting a fine-tuned balance of growth and survival. This anticipation is done by evolving either a high yield mode, or a high growth rate mode. We find that both modes of anticipation can be achieved by individual lineages and by collectives of microbes. Moreover, these different outcomes can be achieved with or without regulation, although the individual-based anticipation without regulation is less well adapted in the high growth rate mode. All our in silico WTs evolve to trust the hand that feeds by evolving to anticipate the periodicity of a serial transfer protocol, but can do so by evolving two distinct growth strategies. Furthermore, both these growth strategies can be accomplished by gene regulation, a variety of different polymorphisms, and combinations thereof. Our work reveals that, even under controlled conditions like those in the lab, it may not be possible to predict individual evolutionary trajectories, but repeated experiments may well result in only a limited number of possible outcomes.


The restriction of codon ambiguity on the basis of known variants.
The genetic code may be used to formulate the nucleotide sequence of a messenger RNA from the known amino acid sequence of a protein. Unfortunately, the degeneracy of the code means that there will be ambiguity in the nucleotide assignments in a third or more of the positions. A simple procedure is given that utilizes the information of known genetic variants to reduce that ambiguity. Problems associated with silent polymorphism are treated. The human alpha and beta hemoglobins are used to exemplify the technique. A total of 68 nucleotides in the two sequences are thereby made less ambiguous. One reduction leads to a nucleotide inconsistent with the result of the recently published beta hemoglobin sequence.


CDK-dependent potentiation of MPS1 kinase activity is essential to the mitotic checkpoint.
Accurate chromosome segregation relies upon a mitotic checkpoint that monitors kinetochore attachment toward opposite spindle poles before enabling chromosome disjunction [1]. The MPS1/TTK protein kinase is a core component of the mitotic checkpoint that lies upstream of MAD2 and BubR1 both at the kinetochore and in the cytoplasm [2, 3]. To gain insight into the mechanisms underlying the regulation of MPS1 kinase, we undertook the identification of Xenopus MPS1 phosphorylation sites by mass spectrometry. We mapped several phosphorylation sites onto MPS1 and we show that phosphorylation of S283 in the noncatalytic region of MPS1 is required for full kinase activity. This phosphorylation potentiates MPS1 catalytic efficiency without impairing its affinity for the substrates. By using Xenopus egg extracts depleted of endogenous MPS1 and reconstituted with single point mutants, we show that phosphorylation of S283 is essential to activate the mitotic checkpoint. This phosphorylation does not regulate the localization of MPS1 to the kinetochore but is required for the recruitment of MAD1/MAD2, demonstrating its role at the kinetochore. Constitutive phosphorylation of S283 lowers the number of kinetochores required to hold the checkpoint, which suggests that CDK-dependent phosphorylation of MPS1 is essential to sustain the mitotic checkpoint when few kinetochores remain unattached.


Comparison of parallel line skin test assay (PLST) and ELISA inhibition (EI) methods for determination of relative potency of polymerized grass and ragweed antigenic extracts.
Relative potency estimates were performed by parallel line skin test assay (PLST) and ELISA inhibition methods for three polymerized allergen extracts (Bermuda grass, orchard grass, and a copolymer of short and giant ragweed) versus four unmodified RAST standardized reference extracts (Bermuda grass, orchard grass, and giant and short ragweed) in nine subjects. One subject experienced a systemic reaction, requiring treatment at the end of the PLST assay. Another subject had a systemic reaction during limited skin testing performed approximately 72 hours after completion of PLST. Relative potency values for the polymerized extracts obtained by PLST were much lower than those obtained by ELISA inhibition, but results were significantly (r = 0.95; p less than 0.01) correlated. Because polymerized allergen extracts are designed to be hypoallergenic, a skin test assay may underestimate their potency relative to an unmodified reference extract.


Performance of anesthesia residents during a simulated prone ventricular fibrillation arrest in an anesthetized pediatric patient.
Exposure to rare pediatric anesthesia emergencies varies depending on the residency program. Simulation can provide increased exposure to these rare events, improve performance of residents, and also aid in standardizing the curriculum. The purpose of this study was to evaluate time to recognize and treat ventricular fibrillation in a pediatric prone patient and to expose learners to the difficulties of managing emergencies in prone patients. Standardized simulation sessions were conducted monthly for 13 months with groups of 1-2 residents in each simulation. The scenario involved a prone patient undergoing posterior spinal fusion. Ventricular fibrillation occurred three minutes into the case. Sessions were viewed by simulation staff, and time to events was recorded. A scripted debriefing followed each case. Evaluations were completed by each participant. The average time to start chest compressions was 77 s, and the average time in recognizing ventricular fibrillation was 76 s. No group performed chest compressions while prone. Only one group defibrillated in the prone position. Participants average time to request defibrillation was 108 s. While nine of 13 groups (69%) ordered an arterial blood gas, only five recognized hyperkalemia, and only four groups gave calcium. Anesthesia residents need additional training in recognizing and treating operative ventricular fibrillation, especially in prone patients and rarely encountered etiologies such as hyperkalemia. Training in the treatment of uncommon pediatric emergencies should be a focal point in anesthesia residency programs.


Integrated miRNA and mRNA expression profiling in fetal hippocampus with Down syndrome.
Down syndrome (DS), caused by triplication of human chromosome 21, is the most common aneuploidies. The main characteristic of DS patients is intellectual disability. MicroRNAs (miRNAs) play important regulatory roles in various biological processes, such as embryonic development, cell differentiation, proliferation and apoptosis. Several miRNAs have shown association with DS. However, the role of miRNAs in DS patients has not been well elaborated. In this research, total RNA extracted from fetal hippocampal tissues was used to analyze miRNA and mRNA expression via Affymetrix miRNA 4.0 and PrimeView Human Gene Expression Array, respectively. Then miRNA and gene expression profiles were integrated by correlation analysis to identify dysregulated miRNAs with their predicted target mRNAs. Microarray data were further validated by real-time PCR. Regulation of zeste homolog 2 (EZH2) expression by hsa-miR-138 was determined by luciferase reporter assay. We analyzed microRNA expression profile in hippocampal tissues from DS fetal using miRNA microarray. Further with the use of mRNA microarray data, we integrate miRNA expression and mRNA expression in hippocampus of trisomy 21 fetus to elucidate the mechanism that underlying DS abnormalities. We characterized the repertoire of specific miRNAs involved in hippocampus in trisomy 21 patients, highlighting hsa-miR-138 and hsa-miR-409, in particular the importance of hsa-miR-138, especially the -5p strand. Furthermore, the expression level of predicted target genes of hsa-miR-138-5p in trisomy 21 fetus, including zeste homolog 2 (EZH2) were further confirmed. In addition, luciferase assay indicated that EZH2 was a direct target of hsa-miR-138 in HEK293T cells. The function of hsa-miR-138-5p and its target EZH2 was involved in hippocampus in DS patients. Our findings provide a clue to study the underlying molecular mechanisms in DS patients, and its potential contribution in improving understanding of intellectual disability development in DS patients.


Feasibility and rationale of a novel approach in advanced ovarian cancer surgery: Bat- shaped en-bloc total peritonectomy and total hysterectomy salpingo-oophorectomy with or without rectosigmoid resection (Sarta-Bat approach).
To evaluate the feasibility of bat-shaped en-bloc total peritonectomy and total hysterectomy-salpingo-oophorectomy with or without rectosigmoid resection as a novel approach in advanced ovarian cancer surgery. Advanced ovarian cancer patients with widespread peritoneal implants requiring total peritonectomy were the subject of the study. Thirteen cases were operated with Sarta-Bat approach between February 2019 and July 2020. Patients' clinical and surgical data were collected and statistically analyzed. Median age of the patients was 52 (40-65). Histopathology of the tumors were high-grade serous carcinoma in 12 (92.3%) and carcinosarcoma in one (7.7%) cases and all of them originated from the ovary. Eight (61.5%), two (15.4%) and three (23.1%) patients were stage 3c, 4a, and 4b, respectively. Upper abdomen was involved in all cases. Nine cases underwent primary cytoreductive and four cases interval cytoreductive surgery. Sarta-Bat approach was performed as en-bloc total peritonectomy, total hysterectomy bilateral salpingo-oophorectomy with rectosigmoid resection in three and without rectosigmoid resection in 10 cases. Final surgery resulted in complete cytoreduction (no macroscopic residual) in all cases, with acceptable grade 2-3 morbidity rates. Sarta-Bat approach is a feasible and convenient technique for cytoreductive surgery of advanced ovarian cancer with disseminated peritoneal metastases.


Magnetic resonance and computed tomography-based scoring system for the differential diagnosis of vertebral fractures caused by osteoporosis and malignant tumors.
Previous reports have described magnetic resonance imaging (MRI) findings alleged to be specific for vertebral fractures caused by malignant lesions. Using such findings for differential diagnosis is often difficult, especially during the early phase of the fracture. With the relative inaccuracy of any single imaging finding, a validated scoring system based on a combination of imaging findings might lead to enhanced diagnostic accuracy. The purpose of this study was to establish a diagnostic scoring system for discriminating osteoporotic vertebral fractures from those caused by malignant tumors on the basis of MRI and computed tomography (CT) findings. Ten MRI and CT scan findings of 57 osteoporotic vertebral fractures and 43 neoplastic fractures were retrospectively evaluated for their ability to discriminate between malignant and benign vertebral fractures. The following four MRI and two CT findings were selected as the basis for the scoring system: pedicle or other posterior element involvement; extension into the paravertebral region; preservation of normal bone marrow signal; a continuous black line representing the posterior vertebral body margin on T2-weighted MRI images; osteolytic destruction; and distinct fracture lines on CT. By combining the findings common to MRI and CT scans of vertebral fractures, a simple scoring system was devised. This scoring system was found to enhance the accuracy of imaging diagnosis of fractures caused by benign or malignant spinal lesions.


Detection of chloramphenicol acetyl transferase activity in transfected cells: a rapid and sensitive HPLC-based method.
An assay based on high-performance liquid chromatography (HPLC) has been developed for determining the expression of the acetyl coenzyme A: chloramphenicol 3-O-acetyltransferase gene in transfected cells. The assay is based on the separation of extracted, nonradioactive chloramphenicol and its acetylated derivatives by reverse-phase HPLC, using UV absorbance for detection. In addition to eliminating the need for costly [14C]chloramphenicol, this assay is as sensitive and much faster than the commonly used method involving thin-layer chromatography.


Vascular malformation of the posterior corpus callosum: surgical treatment.
Arteriovenous malformations in the vicinity of the splenium are a rare cause of subarachnoid bleeding. They are usually unaccompanied by neurological deficits. Three such cases are described and methods of identification and surgical approach discussed. Total extirpation is believed to be the treatment of choice.


Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate.
High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours and has higher affinity and selectivity to the 5-HT(3) receptor. Adult studies have demonstrated that palonosetron is both more effective and require fewer administrations than first generation 5-HT(3) receptor antagonists. The purpose of this study was to examine the effect of a single dose of palonosetron (5 µg/kg) for the prevention of chemotherapy-induced nausea and vomiting in children 18 years of age with ALL treated with HD-MTX, 5 g/m(2). Between January 2010 and December 2010, 138 courses, originating from 53 children, were included from four Danish Childhood Cancer Centers. Information regarding emetic episodes, rescue therapy, and nausea were recorded prospectively on questionnaires. Complete response (no emesis and no rescue therapy) was achieved in 84.1% of courses during the acute (0-24 hours post-chemotherapy) and in 60.1% during the delayed phase (24-66 hours post-chemotherapy). 92.0% of courses were free of emesis during the acute, and 86.2% were free of emesis during the delayed phase. 76.8% of courses were free of nausea during the acute, and 78.3% were free of nausea during the delayed phase. A single dose of palonosetron--without concomitant corticosteroid--was effective in preventing both acute and delayed phase CINV in majority of children with ALL treated with HD-MTX.


Type 2 diabetes mellitus, its treatment and risk for lymphoma.
In this study, we have investigated a potential association between Type 2 diabetes mellitus and its treatment with the risk of lymphoma. Here, we report on 565 incident lymphoma (non-Hodgkin and Hodgkin), multiple myeloma, and chronic lymphocytic leukemia cases and 601 hospital controls in a Spanish multicentric case-control study. Information on diabetes mellitus diagnosis and treatment was obtained through personal interview together with information on other known or putative risk factors for lymphoma. The average age of the study population was 59 years. A medical diagnosis of diabetes was reported by 11% of the controls and 16.3% of cases. Patients with diabetes mellitus not treated with drugs were at an increased risk for lymphoma (OR=1.73, 95%CI=1.11, 2.68), and particularly for multiple myeloma (OR=2.80, 95%CI=1.40, 5.59). Patients treated with insulin had a non-significantly reduced risk for lymphoma (OR=0.70, 95%CI=0.29, 1.67). If replicated, this effect could be explained by a disappearance of hyperinsulinaemia in patients requiring insulin or to the continuous stimulation of the immune system by insulin.


The effect of high and low doses of ochratoxin A in feed on growing chicken.
Effects of high and low dose of ochratoxin A (OTA) as pure toxin supplemented to feed were investigated on the performance of growing chicken. Two groups were fed with different doses of chemical pure OTA 0.5 ppm and 5 ppm in feed and the effects of toxin on body and organ weights were studied and compared with control group. No effects were observed by feeding 0.5 ppm OTA, whereas 5 ppm had a negative effect on the daily body mass gain. OTA in feed had a negative effect on the daily body mass gain. In contrary nephrotoxic effects could be observed by feeding the naturally OTA contaminated feed with only 0.2 ppm of OTA produced byPenicillium verrucosum.


Jejunal enteropathy associated with human immunodeficiency virus infection: quantitative histology.
Jejunal biopsy specimens from 20 human immunodeficiency virus (HIV) positive male homosexual patients were analysed and compared with those of a control group to determine whether the abnormalities were caused by the virus or by opportunistic infection. The degree of villous atrophy was estimated with a Weibel eyepiece graticule, and this correlated strongly with the degree of crypt hyperplasia, which was assessed by deriving the mean number of enterocytes in the crypts. The density of villous intraepithelial lymphocytes fell largely within the normal range, either when expressed in relation to the number of villous enterocytes or in relation to the length of muscularis mucosae. Villous enterocytes showed mild non-specific abnormalities. Pathogens were sought in biopsy sections and in faeces. Crypt hyperplastic villous atrophy occurred at all clinical stages of HIV disease and in the absence of detectable enteropathogens. An analogy was drawn between HIV enteropathy and the small bowel changes seen in experimental graft-versus-host disease. It is suggested that the pathogenesis of villous atrophy is similar in the two states, the damage to the jejunal mucosa in HIV enteropathy being inflicted by an immune reaction mounted in the lamina propria against cells infected with HIV.


Anatomical distribution and functional roles of electrical synapses in Drosophila.
Electrical synapses are present in almost all organisms that have a nervous system. However, their brain-wide expression patterns and the full range of contributions to neural function are unknown in most species. Here, we first provide a light-microscopic, immunohistochemistry-based anatomical map of all innexin gap junction proteins-the building blocks of electrical synapses-in the central nervous system of Drosophila melanogaster. Of those innexin types that are expressed in the nervous system, some localize to glial cells, whereas others are predominantly expressed in neurons, with shakB being the most widely expressed neuronal innexin. We then focus on the function of shakB in VS/HS cells-a class of visual projection neurons-thereby uncovering an unexpected role for electrical synapses. Removing shakB from these neurons leads to spontaneous, cell-autonomous voltage and calcium oscillations, demonstrating that electrical synapses are required for these cells' intrinsic stability. Furthermore, we investigate the role of shakB-type electrical synapses in early visual processing. We find that the loss of shakB from the visual circuits upstream of VS/HS cells differentially impairs ON and OFF visual motion processing pathways but is not required for the computation of direction selectivity per se. Taken together, our study demonstrates that electrical synapses are widespread across the Drosophila nervous system and that they play essential roles in neuronal function and visual information processing.


Phase diagrams of lipid mixtures relevant to the study of membrane rafts.
The present paper reviews the phase properties of phosphatidylcholine-sphingomyelin-cholesterol mixtures, that are often used as models for membrane "raft" microdomains. The available data based on X-ray, microscopic and spectroscopic observations, surface pressure and calorimetric measurements, and detergent solubilization assays, are critically evaluated and rationalized in terms of triangular phase diagrams. The remaining uncertainties are discussed specifically and separately from the data on which a consensus appears to exist.


Metal carcinogenesis: a study of the carcinogenic activity of solid metal alloys in rats.
The carcinogenic activity of seven metallic alloys was studied by implanting solid rods of each alloy in the gluteal muscles of Sprague-Dawley rats which were killed after twenty-four months. When the number of tumors in these rats was compared with the numbers in rats not operated on, in rats which had a sham operation, and in rats implanted with Silastic rods, no statistically significant differences in the incidences of the tumors in the several groups were found.


A comparison of multiple patient reported outcome measures in identifying major depressive disorder in people with multiple sclerosis.
Depression is one of the most prominent and debilitating symptoms in individuals with multiple sclerosis (MS), yet there is currently no consensus on the best instruments for depression screening in MS. More head to head comparisons of available screening instruments are needed to advise MS researchers and clinicians. A cross-sectional comparison of the effectiveness of screening for MDD using multiple patient reported outcome (PRO) screeners against a modified SCID telephone interview was completed in 164 individuals with MS. Stratum goals were set for depression levels to ensure participation by people with borderline and higher levels of depression. Criterion standard was a modified SCID MDD module. PRO measures included the PHQ-9, BDI-FS, PROMIS depression, Neuro-QOL depression, M-PHQ-2, PHQ-2, and CESD. 48 (29%) individuals met the modified SCID criteria for MDD. The sensitivity of the PRO measures ranged from 60% to 100% while specificity ranged from 46% to 86%. The ROC area for the PRO measures ranged from 0.79 to 0.83. Revised (higher) cutoff scores were suggested by the ROC analyses for most self-reported screeners. Enrollment was stopped early because of difficulties with recruitment. Several SCID recording could not be reviewed and diagnosis confirmed. CESD-10 and PHQ9 had the best diagnostic performance using optimal cutoffs, but no one PRO measure stood out as significantly better than any other. Even when revised cutoff scores were used, none of the self-reported screeners identified people with MDD with adequate accuracy. More accurate self-reported screeners would facilitate diagnosing of MDD for both research and clinical purposes.


A new identity can create a new image.
An image study may show that a hospital is failing to project its strengths to area physicians or may indicate that certain departments need to be redefined.


Research on the policy effect and mechanism of green finance to reduce environmental pollution: micro evidence from 285 cities in China.
Based on panel data from 285 Chinese prefecture-level cities from 2003 to 2020, this paper uses the difference-in-difference (DID) method to investigate the policy effect, mechanism, and heterogeneity of green finance (GF) to reduce environmental pollution. (1) Green finance has significant effect on reducing environmental pollution. The parallel trend test demonstrates that DID test results are valid. (2) Following a battery of robustness tests including instrumental variable, propensity score matching (PSM), variable substitution, and changing time-bandwidth, the conclusions are still valid. (3) Mechanism analysis reveals that green finance can reduce environmental pollution by increasing energy efficiency, adjusting industrial structure, and transforming green consumption. (4) Heterogeneity analysis proves that green finance has a substantial impact on reducing the environmental pollution in eastern and western cities, but not in central China. (5) In the "two-control zone" and "low-carbon pilot cities," the results of applying green finance policies are better, and a policy superposition effect exists. To be able to promote environmental pollution control, and green and sustainable development, this paper provides useful enlightenment for environmental pollution control for China and other similar countries.


Normative values of the topological metrics of the structural connectome: A multi-site reproducibility study across the Italian Neuroscience network.
The use of topological metrics to derive quantitative descriptors from structural connectomes is receiving increasing attention but deserves specific studies to investigate their reproducibility and variability in the clinical context. This work exploits the harmonization of diffusion-weighted acquisition for neuroimaging data performed by the Italian Neuroscience and Neurorehabilitation Network initiative to obtain normative values of topological metrics and to investigate their reproducibility and variability across centers. Different topological metrics, at global and local level, were calculated on multishell diffusion-weighted data acquired at high-field (e.g. 3 T) Magnetic Resonance Imaging scanners in 13 different centers, following the harmonization of the acquisition protocol, on young and healthy adults. A "traveling brains" dataset acquired on a subgroup of subjects at 3 different centers was also analyzed as reference data. All data were processed following a common processing pipeline that includes data pre-processing, tractography, generation of structural connectomes and calculation of graph-based metrics. The results were evaluated both with statistical analysis of variability and consistency among sites with the traveling brains range. In addition, inter-site reproducibility was assessed in terms of intra-class correlation variability. The results show an inter-center and inter-subject variability of <10%, except for "clustering coefficient" (variability of 30%). Statistical analysis identifies significant differences among sites, as expected given the wide range of scanners' hardware. The results show low variability of connectivity topological metrics across sites running a harmonised protocol.


About the associations of vitamin D deficiency and biomarkers of systemic inflammatory response with all-cause and cause-specific mortality in a general population sample of almost 400,000 UK Biobank participants.
It is unknown whether the well-known association between vitamin D deficiency and mortality could be explained by the immune system modulating effects of vitamin D, which may protect from a systemic inflammatory response (SIR) to adverse health conditions. This study aims to investigate the interrelationships of vitamin D deficiency, biomarkers of SIR, and mortality. We used multivariate logistic regression with adjustment for 51 covariates to assess the associations of vitamin D deficiency with disadvantageous levels of nine biomarkers of SIR in the UK Biobank cohort. Furthermore, we tested with Cox regression and mediation analysis whether biomarkers of SIR and vitamin D deficiency were independently associated with mortality. We included 397,737 participants aged 37-73 years. Vitamin D deficiency was associated with disadvantageous levels of all blood cell count-based biomarkers, but not with C-reactive protein (CRP)-based biomarkers after adjustment for body weight. Vitamin D deficiency and all biomarkers of SIR were significantly associated with all-cause mortality and mortality from cancer, cardiovascular and respiratory disease. The strength of these associations was unaltered if vitamin D deficiency and biomarkers of SIR were put in the same model. This finding was further supported by the mediation analyses. This study showed that vitamin D deficiency is associated with disadvantageous levels of blood cell count-based but not CRP-based biomarkers of SIR. Vitamin D deficiency and systemic inflammation were independently and strongly associated with mortality. The potential of clinical interventions against both vitamin D deficiency and underlying causes of systemic inflammation should be explored.


Fresh-frozen femoral head allograft as lumbar interbody graft material allows high fusion rate without subsidence.
Circumferential lumbar spinal fusion is widely used to increase fusion rate, but little data is available using fresh-frozen femoral head allograft (FFFHA) as a structural interbody graft alternative. Circumferential lumbar arthrodesis using FFFHA as interbody graft material could be an alternative to achieve interbody fusion without graft subsidence. A retrospective review of 47 patients (56 levels) treated with lumbar circumferential fusion using FFFHA as interbody material. Consolidation was independently assessed by the two authors using a 3-type scale; interbody bone graft subsidence was also evaluated. Forty-four of the 47 patients (93.6%), and 53 of the 56 levels (94.6%) obtained consolidation, without differences between smokers and nonsmokers. Three levels (in three patients) did not fuse; one of them (2.1%) required revision. No patient presented graft dislodgment, signs of infection or graft subsidence at the last follow-up. FFFHA use as lumbar interbody graft in circumferential arthrodesis exhibited a 94% fusion rate, without graft subsidence. FFFHA may be considered a valid alternative to achieve interbody fusion. Level IV. Retrospective study.


Wave mapping: detection of co-existing multiple wavefronts in high-resolution electrical mapping.
High-resolution mapping makes it possible to reconstruct and display the conduction pattern of the action potential as it propagates through cardiac or smooth muscles. During slow and regular activity, time mapping of the spread of activation muscles. During slow and regular activity, time mapping of the spread of activation is relatively simple and straightforward. However, when frequencies are high or conduction is slow, such as seen during atrial fibrillation or found in the pregnant uterus, the tracking of individual waves may become more difficult and uncertain. In order to reconstruct the pathway of a single wave, a search and sorting routine was developed which makes it possible to distinguish, track and display individual wavelets. The algorithm is able to detect variations in conduction block, spontaneous shifts in the location of the pacemaker and changes in the direction of conduction. It is less sensitive when two or more wavefronts intermingle in space and time, such as during collision or fusion. Wave mapping is especially useful, in addition to current time mapping, in sorting quickly through the large amount of data produced by high-resolution mapping of electrical activities in cardiac and smooth muscle.