Polydopamine and calcium functionalized fiber carrier for enhancing microbial attachment and Cr(VI) resistance.
The formation of biofilm determines the performance and stability of biofilm system. Increasing the hydrophilicity of the carrier surface could efficiently accelerate the attachment and growth of microorganisms. Here, the surface of polypropylene (PP) fiber carrier was modified with polydopamine (PDA) and calcium (Ca(II)) to enhance microbial attachment and toxicity resistance. The results of surface characteristic confirmed the self-polymerization of PDA and the chelation mechanism of Ca(II). Subsequently, the biofilm formation experiments were conducted in sequencing batch biofilm reactors using both normal and chromium-containing wastewater. The biofilm on the surface of the modified carrier exhibited better nitrogen removal and Cr(VI) reduction ability. The biomass of the modified carrier was significantly increased, and the maximum microbial attachment amounts in normal wastewater and chrome-containing wastewater were 1153.34 and 511.78 mg/g carrier, respectively. Furthermore, the confocal laser scanning microscope (CLSM) indicated that the modified carrier coated with PDA and Ca(II) were both biocompatible, and the cell activity was significantly increased. 16S rRNA sequencing results showed that the modified carrier efficiently enriched both denitrification bacteria (Thauera and Flavobacterium) and chrome-reducing bacteria (Simplicispira and Arenimonas) to improve system stability and Cr(VI) resistance. Microbial phenotype prediction based on BugBase analysis further verified the enrichment effect of modified carriers on microorganisms responsible for biofilm formation and oxidative stress resistance. Overall, this work proposed a novel functional carrier that could provide references for advancing the application of biofilm systems in wastewater treatment.


Characteristics of the cancer stem cell niche and therapeutic strategies.
Distinct regions harboring cancer stem cells (CSCs) have been identified within the microenvironment of various tumors, and as in the case of their healthy counterparts, these anatomical regions are termed "niche." Thus far, a large volume of studies have shown that CSC niches take part in the maintenance, regulation of renewal, differentiation and plasticity of CSCs. In this review, we summarize and discuss the latest findings regarding CSC niche morphology, physical terrain, main signaling pathways and interactions within them. The cellular and molecular components of CSCs also involve genetic and epigenetic modulations that mediate and support their maintenance, ultimately leading to cancer progression. It suggests that the crosstalk between CSCs and their niche plays an important role regarding therapy resistance and recurrence. In addition, we updated diverse therapeutic strategies in different cancers in basic research and clinical trials in this review. Understanding the complex heterogeneity of CSC niches is a necessary pre-requisite for designing superior therapeutic strategies to target CSC-specific factors and/or components of the CSC niche.


Left Atrial Structural and Functional Response in Kidney Transplant Recipients Treated With Mesenchymal Stromal Cell Therapy and Early Tacrolimus Withdrawal.
Autologous bone marrow-derived mesenchymal stromal cell (MSC) therapy and withdrawal of calcineurin inhibitors (CNIs) has been shown to improve systemic blood pressure control and left ventricular hypertrophy regression in kidney transplant recipients. In the current subanalysis, we aimed to evaluate the impact of this novel immunosuppressive regimen on the longitudinal changes of left atrial (LA) structure and function after kidney transplantation. Kidney transplant recipients randomized to MSC therapy-infused at weeks 6 and 7 after transplantation, with complete discontinuation at week 8 of tacrolimus (MSC group)-or standard tacrolimus dose (control group) were evaluated with transthoracic echocardiography at weeks 4 and 24 after kidney transplantation. The changes in echocardiographic parameters were compared between the randomization arms using an analysis of covariance model adjusted for baseline variable. Fifty-four participants (MSC therapy = 27; tacrolimus therapy = 27) were included. There was no significant interaction between the allocated treatment and the changes of indexed maximal LA volume (LAVImax) over the study period. Conversely, between 4 and 24 weeks post-transplantation, an increase in indexed minimal LA volume (LAVImin) was observed in control subjects, while it remained unchanged in the MSC group, leading to a significant difference between groups (P = .021). Additionally, patients treated with MSC therapy showed a benefit in LA function, assessed by a significant interaction between changes in LA emptying fraction and LA reservoir strain and the randomization arm (P = .012 and P = .027, respectively). The combination of MSC therapy and CNIs withdrawal prevents progressive LA dilation and dysfunction in the first 6 months after kidney transplantation. LAVImin and LA reservoir strain may be more sensitive markers of LA reverse remodeling, compared with LAVImax.


Inducing of automatism of Purkinje fibers with dibutyryl 3', 5' cyclic AMP.
Dibutyryl 3', 5'-cyclic AMP induced automatic activity in Purkinje fibers of myocardial strip in the rat. The phenomenon was not affected by beta adrenergic blockade.


Improved colorimetric assay for detecting influenza B virus neutralizing antibody responses to vaccination and infection.
An automated neutralization test for influenza B virus is described in which antibody titers are determined according to the release of neutral red from infected or uninfected cells of the Madin-Darby canine kidney line. Endpoints are determined in a standard enzyme-linked immunosorbent assay reader. The test requires no expensive immunologic reagents and was used to evaluate responses to both vaccination and natural infection against influenza B virus. Overall responses to vaccination were comparable with those obtained by hemagglutination inhibition, using Tween-ether-split influenza B/Ann Arbor/1/86 virus as the antigen (the HI-TE test). The sensitivities of neutralization responses compared with those obtained by the HI-TE test for two vaccines were 88 and 89%; the specificities were lower at 61 and 60%, respectively. Responses to vaccination, measured by hemagglutination inhibition, were significantly higher with split virus compared with whole virus. However, seroconversion by both the HI-TE and neutralization tests was observed in 5 of 10 individuals from whom virus was detected by either culture of nasal or throat washings or the presence of antigen from immunofluorescence in cells from nasal washings.


Unusual cutaneous adverse reaction to warfarin therapy.
We have described a patient who had an extensive maculopapular pruritic rash after a single dose of warfarin. Although dermatologic reactions have been reported with this drug, the pathogenesis of these reactions remains unknown.


Crusade for iron: iron uptake in unicellular eukaryotes and its significance for virulence.
The effective acquisition of iron is a pre-requisite for survival of all organisms, especially parasites that have a high iron requirement. In mammals, iron homeostasis is meticulously regulated; extracellular free iron is essentially unavailable and host iron availability has a crucial role in the host-pathogen relationship. Therefore, pathogens use specialized and effective mechanisms to acquire iron. In this review, we summarize the iron-uptake systems in eukaryotic unicellular organisms with particular focus on the pathogenic species: Candida albicans, Tritrichomonas foetus, Trypanosoma brucei and Leishmania spp. We describe the diversity of their iron-uptake mechanisms and highlight the importance of the process for virulence.


Differences in the abilities of individual fingers during the performance of fast, repetitive tapping movements.
Using 12 healthy male subjects, the dynamic motor ability of individual fingers was investigated under four different finger tapping conditions. These were: maximum speed tapping with one finger (single-finger tapping), alternate movement of two fingers (double-finger tapping), double-finger tapping in an unsupported condition, and submaximum constant speed tapping with one finger in a passive manner. Key-contact forces for all fingers and the movement velocity of the tapping finger were monitored. With the exception of the unsupported condition, non-tapping fingers were maintained in contact with designated keys during the tapping tasks. It was found that the index finger attained the fastest cadence and greatest movement velocity, followed by the middle, little and ring fingers, respectively. Subjective assessment of rank order of "difficulty" of tapping by the subjects was highly correlated with tapping cadence. Thus dynamic motor function, as indicated by rapid, repetitive movement, differs among the individual fingers. Parallel changes were observed in the key-contact force of the neighboring non-tapping fingers during tapping. The range of the non-tapping finger forces was largest during tapping by the ring finger. A similar trend was found for passive tapping, during which the magnitude of key-contact force was less than one-third of that observed during active tapping. The lower cadence achieved by the ring finger may be attributed more to a lack of independence at the level of voluntary neuromuscular control, than to innate mechanical interaction with the other fingers. Tapping cadence of each finger was lower for the double-finger mode than for the single-finger mode. The magnitude of the observed decrease in cadence during double-finger tapping was, on the other hand, strongly dependent on finger-combination. The decrease was smallest for the index-middle finger-combination, and greatest for the ring-little finger-combination. Compatibilities with other fingers can play an essential role in the dynamic motor function of individual fingers. During the unsupported task, in which interactions were diminished by allowing all fingers to move freely, tapping cadence increased markedly. Therefore, the lower cadences observed in specific finger-combinations may be partly attributed to anatomical and neural interdigit interactions.


Comparison between the effects of diallyl tetrasulfide on human retina pigment epithelial cells (ARPE-19) and HCT116 cells.
Diallyl mono- and polysulfanes from garlic are known to induce an adaptive cell response and the formation of antioxidants in cancer cells. In the case of a severe ER stress and a failure in the response, cancer cells eventually go into apoptosis. Only little is known about the response of normal cells upon treatment. Normal ARPE-19 cells were treated with diallyl tetrasulfide to study their cellular response and the results were compared with those of HCT116 cancer cells. Cell viability was checked by an MTT assay and cytofluorimetry. The formation of superoxide radicals, H2O2 and thiols were determined and proteins involved in the ER stress response were also detected by Western blot analysis. We found that diallyl tetrasulfide induced reactive oxygen species (ROS) in normal cells similar to cancer cells in a time (0 to 60min) and dose dependent manner (0 to 50μM). The level of heme oxigenase-1 (HO-1) was up-regulated in both cell types. Initially, we found a decrease in the total thiol level in both cell types but in contrast to cancer cells, normal cells recovered from the decrease in the total thiol concentration within 60min of treatment. The recovery of the thiol concentration in normal cells treated with diallyl tetrasulfide seems to be responsible for the failure to induce the ER stress signalling pathway and finally apoptosis in normal cells. The difference in the recovery of the thiol status might be an explanation for the anti-carcinogenic effects of garlic compounds.


[Apoptosis of cancer cells induced by influenza virus and its elementary mechanism].
To study the apotosis-inducing effects of influenza virus on cancer cells and the role of FasL. Four strains of cancer cells (Hela, Raji, SMMC-7721 and SPC-A-1) were infected with 20 m. o. i influenza virus and the effects of apoptosis were detected at different time points post infection by electron microscopy, DNA agrose gel electrophoresis, PI stained flow cytometry, and Annexin-V FITC/PI stained flow cytometry. And the concentration of FasL in the culture supernatant was measured with the use of ELISA at the same time. All the four strains of cancer cells showed apoptotic morphological changes. DNA agarose electrophoresis also showed "ladder" in a time dependent manner after virus infection. During this course, there was an obvious increase of FasL concentration in the cell culture supernatant. Influenza virus can induce tumour cells apoptosis in vitro, and it is probably related to the increased expression of FasL.


Improved anticancer efficacy of doxorubicin mediated by human-derived cell-penetrating peptide dNP2.
Although cell penetrating peptides (CPPs) have been extensively studied as an approach to deliver anti-cancer drugs into the tumor cells for the last 30 years, no FDA-approved CPP-based drugs are available, implying that the existing CPPs may have less efficiency in human or have side effects such as toxicity. Herein, we established a tumor targeting drug delivery system by attaching a human-derived cell-penetrating peptide dNP2 (CKIKKVKKKGRKKIKKVKKKGRK) to N-(2-hydroxypropyl)-methacrylamide (HPMA) copolymer doxorubicin conjugates. Firstly, in vitro cytotoxicity of free dNP2 peptide and dNP2-modified blank HPMA copolymer were examined. A classic CPP-R8 (CRRRRRRRR) was chosen for comparison and the results showed that 200 μM free R8 reduced cell viability to 68.4% but dNP2 did not induce any toxicity at the same concentration. After conjugation to HPMA copolymer, a similar trend was also observed which indicated the excellent biocompatibility of dNP2. Next, effect of dNP2 modification on cellular uptake, DNA damage, apoptosis and anticancer activity of HPMA copolymer doxorubicin conjugates were evaluated. It was excited that dNP2 modified HPMA copolymer (P-(dNP2)-DOX) not only had a higher uptake by HeLa cell compared with non-modified copolymer (P-DOX) but resulted in an enhanced drug distribution in nuclei. Furthermore, P-(dNP2)-DOX exhibited greater DNA damage ability (10.5 folds higher than P-DOX) in comet assay and induced more apoptosis cells (46.0%). P-(dNP2)-DOX also showed a stronger cell cytotoxicity (3-fold to P-DOX) as well as in 3D tumor spheroid assay (inhibition rate 78%). All these results suggested that the human-derived cell-penetrating peptide dNP2 could facilitate tumor nuclear-accumulation of anti-cancer drugs and improve anticancer efficacy. More importantly, dNP2 has less toxicity compared with classic CPP-R8 thus shows the potential for the clinic cancer therapy.


The growth of juvenile snails in water conditioned by snails of a different species.
Two species of freshwater snails, Physa acuta and Lymnaea sp. aff. columella, were collected from Asabata marsh, Shizuoka Japan. Individuals of both species inhabit the same plants. Individuals of P. acuta are more abundant than those of L. sp. aff. columella. Experiments were conducted to examine the effect of water conditioned by snails on the growth of 10-day-old juvenile P. acuta snails. Juvenile snails in water conditioned by L. sp. aff. columella grew faster than those in water conditioned by P. acuta or only lettuce. The effects of water conditioned by P. acuta differed among the litters. The results suggest that juvenile P. acuta snails experience accelated growth in the presence of L. sp. aff. columella. The freshwater snails interacted through resource competition as well as through substances disolved in the water.


Endophytic bacterial communities associated with two explant sources of Eucalyptus benthamii Maiden & Cambage.
Micropropagation has been applied in the recovery and rejuvenation of adult trees, which is achieved by various subcultures in the multiplication phase. This strategy has brought questions about the endophytic microbiota associated with these plants along its manipulation. Therefore, the aim of this study was to evaluate the composition of the endophytic bacterial communities associated with two explants sources [the canopy branches (CB) and the trunk base of the tree (TB)] under prolonged in vitro cultivation. In addition we analyzed the bacterial community dynamic along the subcultures in different micropropagation phases. Bacterial DNA was extracted from samples of mini-stumps (in vivo) from CB and TB and in micro-stumps produced by in vitro cultivations of these explants sources--both originated from one single matrix plant of Eucalyptus benthamii. In vitro establishment occurred in two dates and the evaluation of endophytic bacterial communities was made in vivo and in vitro samples (on 10th, 13th and 16th subcultures), when elongated shoots and roots were analyzed. Analysis was performed by PCR-DGGE based on the V6 region of ribosomal gene 16S rDNA. Bands profiles showed differences in communities between in vivo and in vitro samples, and also distinctions of communities assessed in the subcultures, elongated and rooted samples. Distinctions in the composition of endophytic bacterial communities were greater in CB micro-stumps. These results indicate a differential colonization of explants by endophytic bacteria, with predominance of common (ever-present) endophytes in TB samples and casual, here named opportunistic, in CB samples.


Access to new drugs and the global drug-resistant TB crisis: a case series from KwaZulu-Natal, South Africa.
New drugs offer options for patients with drug-resistant tuberculosis (DR-TB). We describe four individuals with DR-TB in KwaZulu-Natal, South Africa, with prior exposure to clofazimine who would benefit from access to delamanid (DLM). Without DLM, individual options are limited, and there is a risk of resistance amplification and both community and nosocomial spread of DR-TB.


Affordable uniform isotope labeling with (2)H, (13)C and (15)N in insect cells.
For a wide range of proteins of high interest, the major obstacle for NMR studies is the lack of an affordable eukaryotic expression system for isotope labeling. Here, a simple and affordable protocol is presented to produce uniform labeled proteins in the most prevalent eukaryotic expression system for structural biology, namely Spodoptera frugiperda insect cells. Incorporation levels of 80% can be achieved for (15)N and (13)C with yields comparable to expression in full media. For (2)H,(15)N and (2)H,(13)C,(15)N labeling, incorporation is only slightly lower with 75 and 73%, respectively, and yields are typically twofold reduced. The media were optimized for isotope incorporation, reproducibility, simplicity and cost. High isotope incorporation levels for all labeling patterns are achieved by using labeled algal amino acid extracts and exploiting well-known biochemical pathways. The final formulation consists of just five commercially available components, at costs 12-fold lower than labeling media from vendors. The approach was applied to several cytosolic and secreted target proteins.


Synthesis, structure and DNA interaction of cobalt(III) bis-complexes of 1,3-bis(2-pyridylimino)isoindoline and 1,4,7-triazacyclononane.
The complex [CoL(2)](ClO(4)).MeOH (1), where HL is the tridentate 3N ligand 1,3-bis(2-pyridylimino)isoindoline, has been isolated and its X-ray crystal structure successfully determined. It possesses a distorted octahedral structure in which both the ligands are coordinated meridionally to cobalt(III) via one deprotonated isoindoline (L(-)) and two pyridine nitrogen atoms. Interestingly, the average dihedral angle between pyridine and isoindoline rings is 25.9 degrees , indicating that the ligand is twisted upon coordination to cobalt(III). The interaction of the complex with calf-thymus DNA has been studied using various spectral methods and viscosity and electrochemical measurements. For comparison, the DNA interaction of [Co(tacn)(2)]Cl(3) (2), where tacn is facially coordinating 1,4,7-triazacyclononane, has been also studied. The ligand-based electronic spectral band of 1 and the N(sigma)-->Co(III) charge transfer band of 2 exhibit moderate hypochromism with small or no blue shift on interaction with DNA. The intrinsic binding constants calculated reveal that the monopositive complex ion [CoL(2)](+) exhibits a DNA-binding affinity lower than the tripositive complex ion [Co(tacn)(2)](3+). The steric clashes with DNA exterior caused by the second L(-) ligand bound to cobalt(III), apart from the lower overall positive charge on the [CoL(2)](+) complex, dictates its DNA-binding mode to be surface binding rather than partial intercalative interaction expected of the extended aromatic chromophore of deprotonated isoindoline anion. An enhancement in relative viscosity of CT DNA on binding to 1 is consistent with its DNA surface binding. On the other hand, a slight decrease in viscosity of CT DNA was observed on binding to 2 revealing that the smaller cation leads to bending (kinking) and hence shortening of DNA chain length. The electrochemical studies indicate that the DNA-bound complexes are stabilised in the higher Co(III) rather than the lower Co(II) oxidation state, suggesting the importance of electrostatic forces of DNA interaction.


Expression of tight junction proteins by umbilical vein epithelial cells co-cultured with allogenic astrocytes.
We studied expression of tight junction proteins and formation of the barrier properties in the culture of umbilical vein endothelial cells under conditions of co-culturing with allogenic GFAP-positive astrocytes. This culturing significantly increases of expression of tight junction proteins (claudin-5, occludin, and ZO-1). The formation of tight junctions significantly increased transendothelial resistance and reduced permeability for sodium fluorescein. Thus, reproducible in vitro model for the study of endothelial barrier properties was created based on co-culturing of umbilical endothelial cells and human astrocytes. This model can be used for evaluation of the permeability of the tissue-blood barriers for substances of different chemical structure and for studies of factors modulating the state of cell-cell contacts.


Dominantly-inherited polycystic kidneys in infants: association with hypertrophic pyloric stenosis.
Newborn male fraternal twins presented at 10 days of age will bilateral flank masses; intravenous urograms showed polycystic kidney disease. Both babies also had hypertrophic pyloric stenosis (HPS). Their father has radiographic and sonographi findings of previously unsuspected polycystic kidneys and has a history of HPS in infancy. The association of dominantly-inherited polycystic kidneys (DPK) and HPS in this family is probably due to chance. However the authors speculate that the autosomal gene for DPK may occur at one of several loci that carry the genetic liability for HPS, A DISORDER TRANSMITTED BY POLYGENIC INHERITANCE.


A new phenolic glycoside from Chamaecyparis obtusa var. breviramea f. crippsii.
A new phenolic glycoside, 3-methoxyphenol 1-O-α-L-rhamnopyranosyl-(1→6)- O-β-D-glucopyranoside (1), was isolated from the 90% acetone extract of the branches and leaves of Chamaecyparis obtusa var. breviramea f. crippsii along with another 10 known phenolics 2-11. Their structures were determined mainly by means of MS, 1D- and 2D-NMR data. Cytotoxicities of compounds 3 and 5-11 were tested on BGC-823, Hela and A549 cancer cell lines, the results showed that compound 8 was bioactive and its IC(50) values were 6.9, 29.7 and 52.9 μM, respectively.


Ploidy dynamics in aphid host cells harboring bacterial symbionts.
Aphids have evolved bacteriocytes or symbiotic host cells that harbor the obligate mutualistic bacterium Buchnera aphidicola. Because of the large cell size (approximately 100 μm in diameter) of bacteriocytes and their pivotal role in nutritional symbiosis, researchers have considered that these cells are highly polyploid and assumed that bacteriocyte polyploidy may be essential for the symbiotic relationship between the aphid and the bacterium. However, little is known about the ploidy levels and dynamics of aphid bacteriocytes. Here, we quantitatively analyzed the ploidy levels in the bacteriocytes of the pea-aphid Acyrthosiphon pisum. Image-based fluorometry revealed the hyper polyploidy of the bacteriocytes ranging from 16- to 256-ploidy throughout the lifecycle. Bacteriocytes of adult parthenogenetic viviparous females were ranged between 64 and 128C DNA levels, while those of sexual morphs (oviparous females and males) were comprised of 64C, and 32-64C cells, respectively. During post-embryonic development of viviparous females, the ploidy level of bacteriocytes increased substantially, from 16 to 32C at birth to 128-256C in actively reproducing adults. These results suggest that the ploidy levels are dynamically regulated among phenotypes and during development. Our comprehensive and quantitative data provides a foundation for future studies to understand the functional roles and biological significance of the polyploidy of insect bacteriocytes.


Finite element analysis to assess stress and deformation in bone with glass fiber-reinforced-poly-ether-ether-ketone, zirconia, and titanium implants.
Recently, zirconia ceramic and glass or carbon fiber-reinforced poly-ether-ether-ketone (PEEK) composites have been introduced as newer implant biomaterials. This study was done to evaluate stress and deformation in bone with glass fiber-reinforced (GFR)-PEEK, zirconia, and titanium implants. A geometric model of mandibular molar replaced with implant-supported crown was generated. Implant of 12 mm length and 4.5 mm diameter was used in study. Finite element analysis models of implant assemblies of three materials GFR-PEEK, zirconium, and titanium were generated. 150 N loads were applied obliquely and vertically along the long axis of implant. Von Mises stresses and deformation generated were compared using ANSYS Workbench 17.0 and finite element software. All three implant assemblies, i.e., GFR-PEEK, zirconia, and titanium, demonstrated similar stresses and deformation in bone without significant difference. It was concluded that GFR-PEEK and zirconia implants can be used as a substitute to titanium implants.


First record of Tettigettalnamariae Quartau & Boulard, 1995 (Insecta: Hemiptera: Cicadoidea) in Spain.
Tettigettalnamariae Quartau & Boulard 1995 is recorded for the first time in Spain. Thought to be endemic to Portugal (occurring in the southern province of Algarve), the present paper adds its distribution to southern Spain, being an Iberian endemism. The acoustic signals of the new specimens collected were recorded in different localities of Huelva province, in Andalusia during August 2012. According to their present known distribution, specimens of Tettigettalnamariae tend to be sparsely distributed in small range populations in southern Iberian Peninsula, favouring wooded areas with Pinuspinea.


Ultrasensitive electrochemical immunosensor for quantitative detection of tumor specific growth factor by using Ag@CeO2 nanocomposite as labels.
In this paper, an ultrasensitive electrochemical immunosensor was developed for the detection of tumor specific growth factor (TSGF). Reduced graphene oxide-tetraethylene pentamine (rGO-TEPA) was used to modify the surface of glassy carbon electrode (GCE). Meanwhile, Ag@CeO2 nanocomposite was synthesized and applied as secondary-antibody (Ab2) labels for the fabrication of the immunosensor. The amperometric response of the immunosensor for the reduction of H2O2 was recorded. Simultaneously, electrochemical impedance spectroscopy (EIS) and Cyclic voltammetry (CV) were used to characterize the fabrication process of the immunosensor. The anti-TSGF primary antibody (Ab1) was immobilized onto the rGO-TEPA modified GCE via cross-linking with glutaraldehyde (GA). And then the TSGF antigen and Ab2-Ag@CeO2 were modified onto the electrode surface in sequence. Under the optimal conditions, the immunosensor exhibited a wide linear range (0.500-100pg/mL), a low detection limit (0.2pg/mL), good reproducibility, acceptable selectivity and excellent stability. The proposed sensing strategy may provide a potential application in the detection of other cancer biomarkers.


Developing fungal pigments for "painting" vascular plants.
The use of fungal pigments as color additives to wood as a method to increase forest revenue is a relatively new, but quickly developing field. Sugar maple (Acer saccharum) is currently the primary utilized hardwood for spalting and appears to be the best suited North American hardwood for such purposes. The combination of Trametes versicolor and Bjerkandera adusta has been identified in several instances as a strong fungal pairing for zone line production; however, Xylaria polymorpha is capable of creating zone lines without the antagonism of a secondary fungus. Few fungal pigments have been developed for reliable use; Scytalidium cuboideum is capable of producing a penetrating pink/red stain, as well as a blue pigment after extended incubation, and Chlorociboria sp. produces a blue/green pigment if grown on aspen (Populus tremuloides). Several opportunities exist for stimulation of fungal pigments including the use of copper sulfate and changes in wood pH.


Independent and court-ordered forensic neuropsychological examinations: official statement of the National Academy of Neuropsychology.
Independent forensic neuropsychological examinations are performed by neuropsychologists who are hired as independent contractors by third parties to make determinations regarding neuropsychological functioning. The responsibilities of neuropsychologists when performing independent or court-ordered forensic examinations differ from those of clinical examinations. Because neuropsychological training typically occurs in clinical contexts, the transition to forensic contexts may result in uncertainty about how to negotiate the unique responsibilities of the forensic examiner role. Neuropsychologists are responsible for maintaining the highest standards of professional practice when performing independent and court-ordered forensic examinations. To reach and maintain the highest standards of practice, neuropsychologists must understand the unique relationships with retaining parties and examinees and strive to maintain true independence and objectivity. Although a true neuropsychologist-patient relationship is not considered to exist within the context of a forensic neuropsychological evaluation, neuropsychologists have ethical responsibilities to both the retaining party and the examinee.


The case for oxygen free radicals in the pathogenesis of ischemic acute renal failure.
One of the more glaring paradoxes of ischemic acute renal failure is that such injury appears to be worse in the kidney as opposed to other organs, even though the kidney is the best oxygenated. An answer can be deduced from the anatomical and physiological background, together with a reappraisal of the role of medullary vascular damage and recent evidence of the importance of the postischemic component of ischemic injury, which is mediated by oxygen free radicals. As far as oxygenation is concerned, the kidney's Achilles heel is the tubules of the outer strip of the outer medulla, which are also those that have the most metabolic activity. It is here that ischemic injury begins, and is maintained and exacerbated in the postischemic stage by the free radicals. These are produced by the kidney in large quantities, since it has all the necessary chemical ingredients available. It is therefore readily understandable why the kidney, being the best oxygenated organ, is so sensitive to an ischemic insult, since the damage caused in the postischemic stage is increased the greater the amount of oxygen brought in by reperfusion.


Serum prolidase activity, oxidative stress, and nitric oxide levels in patients with bladder cancer.
Prolidase is a member of the matrix metalloproteinase family. It plays a major role in collagen turnover, matrix remodeling and cell growth. Nitric oxide (NO) regulates many processes such as collagen synthesis and matrix remodeling. Thus, NO may augment angiogenesis, tumor invasion, and metastasis. The aim of this study was to investigate total antioxidant status (TAS), malondialdehyde (MDA) and NO levels in patients with bladder cancer and to determine their relationship with prolidase activity. Thirty-five patients with bladder cancer and 32 controls were enrolled. Serum TAS, MDA, prolidase activity and NO levels were determined. Serum prolidase activity, NO levels and MDA levels were significantly higher in bladder cancer than controls (all, P < 0.05), while TAS levels were significantly lower (P < 0.05). Our results show that increased prolidase seems to be associated with increased NO levels and oxidative stress along with decreased antioxidant levels in bladder cancer.


Additive and supra-additive cytotoxicity of cisplatin-taxane combinations in ovarian carcinoma cell lines.
The purpose of this study was to compare the growth-inhibitory effect of cisplatin-paclitaxel with that obtained with a cisplatin-docetaxel combination and to assess the type of interaction. Concomitant use of taxanes and cisplatin was studied in seven human ovarian carcinoma cell lines, using the 96-well plate clonogenic assay. Chemosensitivity was expressed in terms of IC50 values, the drug concentration causing 50% inhibition of clonogenic survival. The type of interaction was studied using the area under the survival curve ratios (AUC ratios) obtained by numerical integration. Comparison of the AUC ratio and the surviving fraction (SF) value after taxane alone was made using Student's t-test. The influence of the drug concentration was tested by one-way analysis of variance (Anova). A supra-additive or additive effect was seen when seven ovarian carcinoma cell lines were exposed to paclitaxel or docetaxel concomitantly with cisplatin. A supra-additive effect was found in four cell lines (UT-OC-3, UT-OC-4, UT-OC-5 and SK-OV-3) after simultaneous use of cisplatin with all docetaxel concentrations tested, and in two cell lines (UT-OC-4 and SK-OV-3) when cisplatin was used concomitantly with paclitaxel. A more pronounced supra-additive effect was seen with the combination of cisplatin and docetaxel. The degree of supra-additivity was dose dependent, with increasing synergy after a higher taxane dose. The data obtained in this study suggest that a supra-additive or additive effect can be achieved in ovarian carcinoma with the concomitant use of cisplatin and a taxane.


Protective effect of Polyalthia longifolia var. pendula leaves on ethanol and ethanol/HCl induced ulcer in rats and its antimicrobial potency.
To explore antiulcer and antimicrobial properties of methanolic extract of Polyalthia longifolia var. pendula. Gastroprotective potential of Polyalthia longifolia was studied on ethanol and ethanol/HCl induced ulcers at 2 different doses (270 and 540 mg/kg/body weight). Antimicrobial efficacy of Polyalthia longifolia (25 mg/mL) was also studied against six gram positive, seven gram negative bacteria and five fungi by agar well diffusion method. Minimum inhibitory concentration was determined by agar well diffusion method in two fold serial dilution, in the range of 97-25,000 μg/mL. The reduction of ulcer index in Polyalthia longifolia treated animals was found to be statistically significant with respect to control animals. The Polyalthia longifolia exhibited ulcer protection activity in dose dependent manner and was also better than the standard. In antimicrobial activity, gram positive bacteria were more susceptible to Polyalthia longifolia than gram negative bacteria and fungal strains. Results obtained confirm the antiulcer and antimicrobial potential of the Polyalthia longifolia.


Scales for assessment of depression in schizophrenia: Factor analysis of calgary depression rating scale and hamilton depression rating scale.
This study aimed to evaluate the factor structure of Calgary depression rating scale (CDSS) and Hamilton Depression Rating Scale (HDRS) among patients with schizophrenia in acute and remission phase of illness by using exploratory factor analysis. For this, 267 patients with schizophrenia were assessed on CDSS and HDRS. Exploratory factor analysis of CDSS yielded 2 factor models for the whole sample, patients in clinical remission and patients not in clinical remission phase of schizophrenia. Factor analysis of HDRS yielded 3 factor models; however, there was significant difference in the factor structure between those in clinical remission and those not in clinical remission phase of schizophrenia. CDSS total score did not correlate with PANSS positive and negative subscale scores. In contrast, HDRS total score correlated positively with PANSS positive subscale score, PANSS negative subscale score and PANSS general psychopathology subscale score. To conclude, present study suggests while CDSS items separate out into 2 factors, which are stable across different stages of illness, whereas HDRS factor structure appears to be less stable across different stages of illness. Correlation analysis suggests that rating on HDRS may be affected by positive and negative symptoms of schizophrenia, whereas CDSS do not correlate with positive and negative symptoms of schizophrenia.


Neural alterations in surgical stage chronic pancreatitis are independent of the underlying aetiology.
Among various causes, nerve alterations and neuroimmune interactions have been suggested to participate in the generation of pain in chronic pancreatitis (CP). In this study, we compared neural changes and the pattern of perineural inflammatory cell infiltrates in three different aetiological forms of CP (alcoholic, idiopathic, and tropical) and evaluated whether differences exist between these groups. A total of 35 patients with CP (12 tropical, 12 idiopathic, and 11 alcoholic) were included. Ten normal pancreatic tissues obtained from healthy organ donors served as controls. In all samples, the number of nerves, area of neural tissue, nerve size, and percentage of neural tissue and perineural inflammatory cell infiltrates were analysed histologically. The median number of nerves per 10 mm2 tissue area was 2.3, 4.3, 4.4, and 2.6 in the normal pancreas, alcoholic CP, idiopathic CP, and tropical CP, respectively. Median area of neural tissue per 10 mm2 was 2550, 21 803, 18 595, and 24 666 microm2 in the normal pancreas, alcoholic CP, idiopathic CP, and tropical CP, respectively. Median nerve diameter was 36.85 microm in the normal pancreas, 80.6 microm in alcoholic CP, 68.95 microm in idiopathic CP, and 93.05 microm in tropical CP. In comparison with normal controls, all of these parameters were significantly increased except the number of nerves in tropical CP. For all parameters there were no significant differences between alcoholic, idiopathic, and tropical CP. When the degree of perineural inflammation was evaluated, no differences were observed among the three CP groups. Independent of the underlying aetiology, CP is associated with an increase in neural tissue, and neural alterations occur in a similar fashion irrespective of the type of initiating event.


A Multi-responsive Fluorescent Probe Reveals Mitochondrial Nucleoprotein Dynamics with Reactive Oxygen Species Regulation through Super-resolution Imaging.
Understanding the biomolecular interactions in a specific organelle has been a long-standing challenge because it requires super-resolution imaging to resolve the spatial locations and dynamic interactions of multiple biomacromolecules. Two key difficulties are the scarcity of suitable probes for super-resolution nanoscopy and the complications that arise from the use of multiple probes. Herein, we report a quinolinium derivative probe that is selectively enriched in mitochondria and switches on in three different fluorescence modes in response to hydrogen peroxide (H2 O2 ), proteins, and nucleic acids, enabling the visualization of mitochondrial nucleoprotein dynamics. STED nanoscopy reveals that the proteins localize at mitochondrial cristae and largely fuse with nucleic acids to form nucleoproteins, whereas increasing H2 O2 level leads to disassociation of nucleic acid-protein complexes.


Morphological and molecular heterogeneity of epithelial ovarian cancer: Therapeutic implications.
Ovarian epithelial cancer (OEC) is the most lethal gynecologic malignancy. Despite current chemotherapeutic and surgical options, this high lethality can be attributed to multiple factors, including late-stage presentation. In order to optimize OEC treatment, it is important to highlight that it is composed of five main subtypes: high-grade serous ovarian carcinoma (HGSOC), low-grade serous ovarian carcinoma (LGSOC), endometrioid ovarian carcinoma (EOC), ovarian clear cell carcinoma (CCOC), and mucinous ovarian carcinoma (MOC). These subtypes differ in their precursor lesions, as well as in epidemiological, morphological, molecular and clinical features. OEC is one of the tumours in which most pathogenic germline mutations have been identified. Accordingly, up to 20% OC show alterations in BRCA1/2 genes, and also, although with a lower frequency, in other low penetrance genes associated with homologous recombination deficiency (HRD), mismatch repair genes (Lynch syndrome) and TP53. The most important prognostic factor is the 2014 FIGO staging, while older age is also associated with worse survival. HGSOC in all stages and CCC and MOC in advanced stages have the worse prognosis among histological types. Molecular markers have emerged as prognostic factors, particularly mutations in BRCA1/2, which are associated with a better outcome. Regarding treatment, whereas a proportion of HGSOC is sensible to platinum-based treatment and PARP inhibitors due to HRD, the rest of the histological types are relatively chemoresistant. New treatments based in specific molecular alterations are being tested in different histological types. In addition, immunotherapy could be an option, especially for EOC carrying mismatch repair deficiency or POLE mutations.


The Neer II replacement for rheumatoid arthritis of the shoulder.
Thirty-eight patients had a Neer II replacement for rheumatoid arthritis of the shoulder. The average age at operation varied from 23 to 68 years. The average follow-up was 20.9 months. Forty shoulders were free of pain and function was reasonable in 21. Overall evaluation showed an excellent or satisfactory result in 15, 16, were acceptable and 10 poor. The most frequent radiological finding was upward subluxation which was present in 20 shoulders. An incomplete radiolucent zone was found around the glenoid component in 32% and around the humeral in 5%; there was no gross loosening.


Different Renal Function Equations and Dosing of Direct Oral Anticoagulants in Atrial Fibrillation.
Randomized trials of direct oral anticoagulants (DOACs) adopted the Cockcroft-Gault (CG) formula to calculate estimated glomerular filtration rate (eGFR) to determine the dosages of DOACs. The authors aimed to investigate the agreements/disagreements of eGFRs calculated using different equations (CG, Modified Diet in Renal Disease [MDRD], and Chronic Kidney Disease Epidemiology Collaboration [CKD-EPI] formulas), and their impacts on the dosages of DOACs and clinical outcomes. Medical data from a multicenter health care provider in Taiwan including 39,239 patients with atrial fibrillation were used. Among these patients, there were 11,185 and 2,323 patients treated with DOACs and warfarin, respectively. At the cutoff values of eGFR of <15, 15-50, and >50 mL/min, the agreements were 78% between MDRD and CG and 81% between CKD-EPI and CG. The disagreements among the different equations were largely due to overestimations, especially for patients aged >75 years and with a body weight of <50 kg (58.8% for MDRD and 50.9% for CKD-EPI). Among patients receiving DOACs whose dosages were defined as "on label" based on MDRD or CKD-EPI, only those whose dosages were "truly on label" based on CG were associated with a lower risk of major bleeding (adjusted HR: 0.34; 95% CI: 0.26-0.45) compared to warfarin. The adoptions of MDRD or CKD-EPI rather than CG would result in inappropriate dosing of DOACs (mainly overdosing), which would attenuate the advantages of DOACs compared to warfarin. The CG equation should be used as the gold standard to calculate eGFRs and guide the DOAC dosages.


Synaptosomal uptake and release of dopamine in substantia nigra: effects of gamma-aminobutyric acid and substance P.
Nigral tissue prepared as synaptosomes demonstrates both high and low affinity uptake of [3H]dopamine. Recently accumulated [3H]dopamine is releasable by 35 mN K+. Substance P increases both uptake and release of dopamine by nigral synaptosomes; gamma-aminobutyric acid (GABA) inhibits release with no effect on uptake at concentrations less than 10-(4) M. In the striatum, substance P inhibits both uptake and release of dopamine. The results support the existence of dopamine-containing terminals in substantia nigra tissue. The differences in response to substance P and GABA found between nigra and striatum may reflect structural differences in dopamine-containing processes in these areas, related to their proposed origin as dendtritic (substantia nigra) and axonal (striatal) terminal.


Effects of cognitive stimulation therapy on patients with dementia: An umbrella review of systematic reviews and meta-analyses.
Dementia is characterized by significant cognitive decline that results in disturbance of daily activities. Increasing number of meta-analyses has examined the efficacy of cognitive stimulation therapy (CST) for dementia. However, there is a lack of comprehensive reports that specifically discuss the strength of evidence to support CST for dementia. This study aimed to summarize evidence regarding the efficacy of CST on people with dementia. Umbrella review of systematic reviews and meta-analyses. We searched Cochrane Library, PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Web of Science, China National Knowledge Infrastructure (CNKI), Wanfang Data, China Biology Medicine disc (CBMdisc), and VIP databases from inception to December 31, 2022. The methodological quality of the identified studies was assessed using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2). Studies scoring 9-12 (moderate quality) points or higher were further analyzed using Grades of Recommendations Assessment, Development and Evaluation (GRADE) principles. A total of 14 systematic reviews and meta-analyses were included in the umbrella review. The methodological quality of most included reviews was rated as moderate according to AMSTAR 2 rating system. In these studies, we summarized the characteristics of the content, providers, frequency, period and setting of CST, and examined eight health outcomes related to CST, including cognition, depression, behavioral symptoms, quality of life (QoL), activities of daily living (ADL), language and communication, anxiety, and memory. Eleven studies with low to high rating of overall confidence (OC) consistently reported that CST could significantly improve cognition of people with dementia, including high-quality supporting evidence. However, the effect of CST on other health outcomes for people with dementia (e.g., depression, behavioral symptoms, QoL, ADL) is inconsistent, with low- to moderate-quality evidence ratings. Compared with the above results, few studies have reported the effects of CST on communication, anxiety, and memory for people with dementia. In the future, the design and reporting of systematic reviews and meta-analyses should incorporate high-quality research metrics in accordance with AMSTAR 2 criteria. The current review supports CST as an effective treatment for improving cognitive function in patients with dementia. Multi-component interventions are more effective than single-component interventions and need to be delivered regularly. The protocol was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database (CRD42022364259).


Two-year survival, mental, and motor outcomes after cardiac extracorporeal life support at less than five years of age.
Comprehensive outcome assessment of children receiving cardiac extracorporeal life support. From 2000 to 2004, 39 consecutive children (aged 1 day to 4.4 years) had cardiac extracorporeal life support. Neurodevelopmental follow-up of all survivors was performed more than 6 months after life support (aged 53 +/- 12 months). Developmental delay was defined as a score of less than 70 on the Bayley Scales of Infant Development II or Wechsler Preschool and Primary Scale of Intelligence. Predictor variables for mortality (at 2 years' follow-up) and delay were examined by univariate and multivariate analyses. Indications for extracorporeal life support were progressive low cardiac output in 14 (36%), failed weaning from cardiopulmonary bypass in 13 (33%), cardiac arrest in 9 (23%), and hypoxia in 3 (8%). Cardiac anatomy was single ventricle in 16 (41%), biventricular in 21 (54%), and myocarditis in 2 (5%). Survival was 18 (46%) at hospital discharge and 16 (41%) at 2 years. In survivors, mental score was 73 +/- 16 (normal 100 +/- 15), and 8 (50%) had mental delay. Initiating extracorporeal life support during cardiopulmonary resuscitation and duration of this resuscitation were not associated with death or mental delay. On multivariable Cox regression, lactate on admission to the pediatric intensive care unit (hazard rate 1.13; 95% confidence intervals 1.08-1.27) and single ventricle anatomy (hazard rate 3.93; 95% confidence intervals 1.62-9.49) were associated with death at 2 years. Stepwise multiple regression found time for lactate to normalize on extracorporeal life support, highest inotrope score during 120 hours of life support, and chromosomal abnormality explained 76.7% of the variance in mental score. Cardiac extracorporeal life support had a 41% 2-year survival. Potentially modifiable variables (time for lactate to normalize and highest inotrope score early during extracorporeal life support) explained 69% of mental score variance.


Rapid resolution of migraine symptoms after initiating the preventive treatment eptinezumab during a migraine attack: results from the randomized RELIEF trial.
Eptinezumab is an anti-calcitonin gene-related peptide (CGRP) monoclonal antibody approved for the preventive treatment of migraine. In the phase 3 RELIEF study, eptinezumab resulted in shorter time to headache pain freedom and time to absence of most bothersome symptom (MBS; including nausea, photophobia, or phonophobia) compared with placebo when administered during a migraine attack. The objective of this exploratory analysis was to examine the earliest time points that eptinezumab separated from placebo (P < .05) on headache- and migraine-associated symptoms when administered during a migraine attack. RELIEF, a multicenter, parallel-group, double-blind trial, occurred from November 7, 2019, through July 8, 2020. Adults considered candidates for preventive treatment were randomized to eptinezumab 100 mg (N = 238) or placebo (N = 242) administered intravenously over 30 min within 1-6 h of migraine onset. Outcome measures included headache pain freedom/relief and absence of MBS, patient's choice of photophobia, phonophobia, or nausea, at regular intervals from 0.5 to 48 h after infusion start. Censoring was applied at time of acute rescue medication use. At hour 1, more eptinezumab-treated patients achieved headache pain freedom (9.7%), headache pain relief (38.7%), and absence of MBS (33.2%) versus placebo (4.1%, 26.9%, and 22.1%, respectively; P < .05 all), with separation from placebo (P < .05) through hour 48. Eptinezumab separated from placebo (P < .05) at hour 1 in absence-of-photophobia (29.4% vs 17.0%) and absence-of-phonophobia (41.2% vs 27.2%) and through hour 48. Initial separation from placebo (P < .05) in absence-of-nausea occurred at end-of-infusion (0.5 h; 36.7% vs 25.4%, respectively). Preventive treatment with eptinezumab initiated during a migraine attack resulted in more patients achieving headache pain freedom/relief and absence of MBS, with separation from placebo (P < .05) as early as 0.5-1 h following the start of infusion. Rapid resolution of headache- and migraine-associated symptoms by a peripherally acting, intravenously administered antibody suggest a peripheral site of pharmacological action for CGRP blockade. ClinicalTrials.gov Identifier: NCT04152083 .


Neonatal mortality risk of vulnerable newborns: A descriptive analysis of subnational, population-based birth cohorts for 238 203 live births in low- and middle-income settings from 2000 to 2017.
We aimed to understand the mortality risks of vulnerable newborns (defined as preterm and/or born weighing smaller or larger compared to a standard population), in low- and middle-income countries (LMICs). Descriptive multi-country, secondary analysis of individual-level study data of babies born since 2000. Sixteen subnational, population-based studies from nine LMICs in sub-Saharan Africa, Southern and Eastern Asia, and Latin America. Live birth neonates. We categorically defined five vulnerable newborn types based on size (large- or appropriate- or small-for-gestational age [LGA, AGA, SGA]), and term (T) and preterm (PT): T + LGA, T + SGA, PT + LGA, PT + AGA, and PT + SGA, with T + AGA (reference). A 10-type definition included low birthweight (LBW) and non-LBW, and a four-type definition collapsed AGA/LGA into one category. We performed imputation for missing birthweights in 13 of the studies. Median and interquartile ranges by study for the prevalence, mortality rates and relative mortality risks for the four, six and ten type classification. There were 238 203 live births with known neonatal status. Four of the six types had higher mortality risk: T + SGA (median relative risk [RR] 2.6, interquartile range [IQR] 2.0-2.9), PT + LGA (median RR 7.3, IQR 2.3-10.4), PT + AGA (median RR 6.0, IQR 4.4-13.2) and PT + SGA (median RR 10.4, IQR 8.6-13.9). T + SGA, PT + LGA and PT + AGA babies who were LBW, had higher risk compared with non-LBW babies. Small and/or preterm babies in LIMCs have a considerably increased mortality risk compared with babies born at term and larger. This classification system may advance the understanding of the social determinants and biomedical risk factors along with improved treatment that is critical for newborn health.


Generation and characterization of a human induced pluripotent stem cell line (SDQLCHi052-A) from peripheral blood mononuclear cells derived from a healthy Chinese donor.
A non-integrated induced pluripotent stem cell (iPSC) line was generated derived from a healthy 20-day-old male using peripheral blood mononuclear cells. The established induced pluripotent stem cell line possesses a normal karyotype, expresses pluripotency markers and able to differentiate into all three germ layers in vitro. This cell line could serve as a health control or a basis for disease modeling, to explore molecular pathogenesis.


Acute internal carotid artery occlusion due to dissection of the paraclinoid segment: Diagnostic usefulness of angiographic findings during stent retriever deployment.
Intracranial artery dissection is an uncommon but possible cause of ischemic stroke, and is usually diagnosed based on imaging findings such as mural hematoma and dissection flap. However, it is challenging to recognize the underlying dissection in cases of acute large vessel occlusion. In this report, we present a case of acute internal carotid artery occlusion, in which the underlying dissection of the paraclinoid segment was found during the thrombectomy procedure. Two thrombectomy procedures failed to recanalize the acute internal carotid artery occlusion without removing any clot. Angiography performed during a Trevo stent retriever deployment in the first pass showed obscure contrast defects in the stent strut with temporary flow restoration. In the next pass, the appearance of the contrast defects changed and a parallel linear contrast appeared on the outside of the vessel wall. These angiographic findings were identified as mural hematoma and dissection flap, indicating dissection of the paraclinoid as the cause of the occlusion. During antiplatelet loading and preparation of a dedicated intracranial stent, the Trevo stent retriever was left deployed again at the occlusion site to maintain the blood flow. After permanent stenting with an Enterprise stent, angiography revealed complete recanalization. The patient recovered fully after the procedure. In the present case, stent retriever deployment revealed the hallmarks of dissection on angiography, such as mural hematoma, dissection flap, and temporal morphological changes, by restoring the blood flow temporarily. Such angiographic findings can provide useful information on the occlusion characteristics and real-time feedback for optimal treatment strategy.


Trend of soft contact lens prescribing in an optometry centre in India: a 6-year analysis.
This six-year retrospective longitudinal study was conducted to examine the changes in the pattern of prescribing soft contact lenses in an optometry centre located in a University in South India. Details regarding the type of lenses, lens material, wearing pattern and the clinical diagnoses were analyzed from January 2006 to December 2011. A total of 1273 soft contact lens fits (n=1273) were analyzed. Two-third of the total lenses dispensed was for females and their mean age (24.0±8.3 yrs) was less than that of male (27.0±11.2 yrs) lens users. Nearly 70% of them had myopia and 48% wore conventional soft contact lenses. During the studied six years, the percentage of conventional lenses declined by 60%. This study demonstrated a gradual and significant increase in popularity of disposable contact lenses and silicone hydrogel lens material which is comparable to the global trend.


Pediatric pyosalpinx without sexually transmitted infection: A report of 3 cases.
Pelvic inflammatory disease commonly occurs in adults and is most frequently caused by sexually-transmitted organisms. When left untreated, it can progress to abscess formation and subsequent infertility due to tubal scarring. This condition rarely occurs in the pediatric population and even less frequently in the absence of sexual activity. The cases presented here depict 3 cases of pyosalpinx due to noncommunicable infectious agents. Since children are typically not subjected to transvaginal ultrasound, they are particularly at risk for delays in diagnosis and appropriate treatment. Cases described here also demonstrate the value of the pediatric interventional radiology service in treating this gynecological source of infection. Both transabdominal and transrectal approached to ultrasound-guided drainage are described.


Postconcussional Syndrome: Clinical Diagnosis and Treatment.
Diagnosis and treatment of postconcussional syndrome (PCS) is challenging because symptoms are vague, difficult to confirm, and attributable to other conditions. There are no uniformly accepted diagnostic PCS criteria. Clinical care largely focuses on symptom reduction and management. Moreover, the coronavirus disease 2019 (COVID-19) pandemic has increased the challenge because post-acute COVID-19 syndrome symptoms overlap with PCS. Future research should center on base rates of PCS-type symptoms in nonneurological samples and the identification and improved understanding of moderating variables contributing to the frequency, intensity, and duration of PCS symptoms.


Factors associated with opioid prescriptions among women proximal to pregnancy in the United States.
Pregnant women are a vulnerable population exposed to opioids in the United States. To examine trends and factors associated with opioid prescribing to women proximal to pregnancy. The 2011 to 2015 Medical Expenditure Panel Survey (MEPS) was used to identify participants (n = 3020) with self-reported pregnancy or pregnancy-relevant events aged between 18 and 44 years old. To investigate factors associated with opioid prescriptions, we categorized participants into two subgroups: having one or more opioid prescription or having none during the observational period. We used survey multivariable logistic regression to identify factors associated with opioid prescribing accounting for the complex survey design in MEPS. From 2011 to 2015, the prevalence of opioid prescribing among study participants was 31%. Opioids were more likely to be prescribed to women who had psychiatric conditions (odds ratio, 1,76, 95%CI: 1.27-2.44, p < 0.001). Other significant factors included being non-Hispanic white or black, living in the South, active tobacco users, and those with lower Physical Component Summary Scores. Receipt of an opioid prescription in the perinatal period is associated with maternal psychiatric disorders in the United States. Study findings add new data to the literature on opioid use among pregnant women and provide evidence for healthcare providers and policy makers to tailor treatment and educational programs to avoid opioid overuse among pregnant women.


Effect of a new de-N-acetyl-lysoglycosphingolipid on chemically-induced inflammatory bowel disease: possible mechanism of action.
A new, orally active de-N-acetylated lysoglycosphingolipid (WILD20) was evaluated as antiinflammatory agent using a model of chemically-induced inflammatory bowel disease (IBD) in the rat to mimic human ulcerative colitis and Chron's disease. IBD was induced by hapten trinitrobenzenesulphonic acid (TNB). WILD20, orally administered as preventive or curative, was demonstrated to be efficacious at daily dosages of 0.1-1 mg/kg for 4-5 days. Damage scores, body weight, spleen weight, colonic tissular levels of LTB4, myeloperoxidase (MPO) and malondialdehyde (MDA) are influenced and brought into parameters of normality. Histological observation demonstrated quicker healing, better repair, reduced inflammation, and poor eosinophil degranulation. The mechanisms underlying WILD20 antiinflammatory effects were investigated: whereas WILD20 fails to show a direct effect on PKC, it reduces PKC translocation to the membrane; cellular PLA2 was consequently greatly reduced through this mechanism and thought to be responsible for WILD20 efficacy towards chemically-induced IBD.


Cost-effectiveness of transabdominal ultrasound for cervical length screening for preterm birth prevention.
Transabdominal ultrasound (TAUS) cervical length (CL) screening has been proposed as an alternative to universal transvaginal screening to identify women at an increased risk of preterm birth. We sought to identify whether and under what circumstances TAUS would be cost-effective. This is a decision analytic model designed to compare an initial TAUS CL screening approach with universal transvaginal screening in a hypothetical cohort of women with a singleton pregnancy. Cost, probability, and utility estimates were derived from the existing literature. Under baseline assumptions, universal transvaginal was the dominant strategy. In comparison to TAUS, universal transvaginal CL screening reduced preterm birth by 0.03%, reduced costs by $1.2 million and increased quality-adjusted life years by 70 per 100,000 women. Although robust to many changes in many estimates, the model was sensitive to the cost of a transvaginal ultrasound, the prevalence of a short cervix and the test characteristics (ie, sensitivity and specificity) of a TAUS screening examination for short CL. Compared with an initial TAUS screen, universal transvaginal ultrasound was a more cost-effective strategy under most assumptions. Optimizing TAUS testing characteristics or applying a transabdominal screening strategy in lower risk populations may yield an initial TAUS to be cost-effective.


GyrI: a counter-defensive strategy against proteinaceous inhibitors of DNA gyrase.
DNA gyrase is the target of two plasmid-encoded toxins CcdB and microcin B17, which ensure plasmid maintenance. These proteins stabilize gyrase-DNA covalent complexes leading to double-strand breaks in the genome. In contrast, the physiological role of chromosomally encoded inhibitor of DNA gyrase (GyrI) in Escherichia coli is unclear and its mechanism of inhibition has not been established. We demonstrate that the mode of inhibition of GyrI is distinct from all other gyrase inhibitors. It inhibits DNA gyrase prior to, or at the step of, binding of DNA by the enzyme. GyrI reduces intrinsic as well as toxin-stabilized gyrase-DNA covalent complexes. Furthermore, GyrI reduces microcin B17-mediated double-strand breaks in vivo, imparting protection to the cells against the toxin, substantiating the in vitro results. Thus, GyrI is an antidote to DNA gyrase-specific proteinaceous poisons encoded by plasmid addiction systems.


Clinical Practice Guideline Recommendations For Pediatric Multisystem Trauma Care: A Systematic Review.
To systematically review clinical practice guidelines (CPGs) for pediatric multisystem trauma, appraise their quality, synthesize the strength of recommendations and quality of evidence, and identify knowledge gaps. Traumatic injuries are the leading cause of death and disability in children, who require a specific approach to injury care. Difficulties integrating CPG recommendations may cause observed practice and outcome variation in pediatric trauma care. We conducted a systematic review using Medline, Embase, Cochrane Library, Web of Science, ClinicalTrials, and grey literature, from January 2007 to November 2022. We included CPGs targeting pediatric multisystem trauma with recommendations on any acute care diagnostic or therapeutic interventions. Pairs of reviewers independently screened articles, extracted data, and evaluated the quality of CPGs using "Appraisal of Guidelines, Research, and Evaluation II." We reviewed 19 CPGs, and 11 were considered high quality. Lack of stakeholder engagement and implementation strategies were weaknesses in guideline development. We extracted 64 recommendations: 6 (9%) on trauma readiness and patient transfer, 24 (38%) on resuscitation, 22 (34%) on diagnostic imaging, 3 (5%) on pain management, 6 (9%) on ongoing inpatient care, and 3 (5%) on patient and family support. Forty-two (66%) recommendations were strong or moderate, but only 5 (8%) were based on high-quality evidence. We did not identify recommendations on trauma survey assessment, spinal motion restriction, inpatient rehabilitation, mental health management, or discharge planning. We identified 5 recommendations for pediatric multisystem trauma with high-quality evidence. Organizations could improve CPGs by engaging all relevant stakeholders and considering barriers to implementation. There is a need for robust pediatric trauma research, to support recommendations.


Multistep mechanism of chloride translocation in a strongly anion-selective porin channel.
The strongly anion-selective porin channel Omp32 from the bacterium Delftia acidovorans differs from other unspecific porins by its pronounced selectivity for anions and its particularly small channel cross-section. Multinanosecond molecular dynamics simulations of chloride ion movement in this pore protein suggest that translocated anions interact intimately with the charges of a "basic ladder", whose dynamics lead the anions in a stepwise manner through the constriction zone of the channel. The ladder-steps comprise the central clustered arginine groups and flanking basic residues at its exoplasmic and periplasmic sides. The computed free energy profile of ion movement in and around the constriction zone shows a corresponding succession of free energy minima and barriers. A number of polar atoms from other amino acids contribute to the coordination of Cl(-) at certain sites and to its temporary immobilization in the channel. A special binding site occurs at the transition of the constriction zone to the periplasmic funnel, binding the chloride ion over significant lengths of time. The results from our MD study offer a possible explanation for the nonlinear conductance properties and unusual salt-dependent characteristics of Omp32 observed earlier in experimental measurements.


Renal function adaptation up to the fifth decade after treatment of children with unilateral renal tumor: a cross-sectional and longitudinal study.
Mild-to-moderate renal function loss may be an independent risk factor for cardiovascular disease and overall mortality. As in adults with renal carcinoma nephrectomy is associated with an high risk for moderate renal function loss, we aimed to assess the renal function adaptation over a long period of time in children with unilateral renal tumor (URT). Seventy-two children who underwent surgery for URT were enrolled in this study. Glomerular filtration rate was estimated (eGFR) with the Modification of Diet in Renal Study or the Schwartz equation, as appropriate for the age. Twelve patients treated by nephron-sparing surgery (Group A) and 42 treated by nephrectomy (Group B) had an age between 2 and 30 years; 18 patients treated by nephrectomy had an age between 33 and 51 years (Group C). At cross-sectional follow-up 8% patients of Group A, 42% of Group B and 78% of Group C presented a mild-to-moderate renal function. The longitudinal data stratified by post-operative intervals showed that patients of Group C presented a significant progressive decrease in mean ± standard deviation eGFR (88.1 ± 22.6 during the third decade after surgery vs. 66.6 ± 15.6 ml/min/1.73 m(2) during the fifth decade after surgery; P = 0.02). The longitudinal data stratified by age showed that patients with an age between 45 and 54 years presented a mean eGFR significantly lower than that expected for the physiological renal function decline with aging (P = 0.001). Aging is associated with a mild-to-moderate renal function loss in many adult patients following nephrectomy during childhood for URT.


Misclassification and the design of environmental studies.
Many authors have documented the existence of effects due to misclassification. This paper examines the size of these effects in the context of environmental studies. Misclassification occurs because of the use of surrogate measures of exposure. Misclassification causes relative risks to appear smaller than they are, with larger relative risks being seriously affected. The power of statistical tests is reduced, but not as seriously.


Fused labia. Clinical and radiological findings.
The clinical and radiological findings in fused labia are described. Some of the patients were asymptomatic. The others were referred because of a suspicion of urinary infection. Micturating cystourethrography showed collection of contrast material above the labia and marked reflux into the vagina in all patients examined. These findings were not seen after separation of the labia. Although the diagnosis is usually a clinical one, it is suggested that labial fusion may first be recognized by the radiologist through these cystourethrographic findings and while catheterizing the child.


Secretory component in differentiating normal epithelium, benign lesions and malignancy in the human breast as monitored by monoclonal antibodies.
An immunohistochemical study of the expression of the secretory component (SC) in human mammary gland epithelium at various stages of differentiation, as well as in benign and malignant breast tumours, was undertaken using three mouse monoclonal antibodies. Antibody RICEO-SC-05 (SC-05), raised against a partially purified preparation of human SC, and reacting with a reduction-resistant epitope present in both free and polymeric immunoglobulin-bound SC, was compared in immunoperoxidase and immunofluorescence studies on a diverse range of normal tissues, to 2 reference anti-SC antibodies (LICR-LONLC28 and RICEO-MFG-12). All three antibodies reacted with secretory epithelia only, consistent with known patterns of expression of SC in tissues, although there was an unexpected reaction by all anti-SC antibodies with some Hassal's corpuscles of the thymus. Staining patterns seen in the normal resting, pregnant, lactating and regressing (after weaning) breast provide evidence for differentiation-associated changes in the production of SC, and support the concept of terminal ductal lobular units (TDLUs) as functional compartments of the mammary gland. SC was detected in all but one benign breast lesion (n = 53) as compared to only 24% positive cases with heterogeneous expression of SC found among 176 primary and metastatic breast carcinomas examined. In a series of 40 primary breast carcinomas and their corresponding lymph node metastases, a good overall correlation was found between the expression of SC in the matched specimens; aside from 3 heterogeneously SC-positive carcinomas whose metastatic counterparts were SC-negative. Our results demonstrate a potential application for monoclonal antibodies to SC in the study of human mammary gland differentiation, but suggest that the value of an assay for SC in the diagnosis of breast carcinomas is questionable due to the generally low expression of SC by either primary or metastatic breast lesions.


Functional segregation of the inferior frontal gyrus for syntactic processes: a functional magnetic-resonance imaging study.
We used functional magnetic resonance imaging in 18 normal volunteers to determine whether there is separate representation of syntactic, semantic, and verbal working memory processing in the left inferior frontal gyrus (GFi). We compared a sentence comprehension task with a short-term memory maintenance task to identify syntactic and semantic processing regions. To investigate the effects of syntactic and verbal working memory load while minimizing the differences in semantic processes, we used comprehension tasks with garden-path (GP) sentences, which require re-parsing, and non-garden-path (NGP) sentences. Compared with the short-term memory task, sentence comprehension activated the left GFi, including Brodmann areas (BAs) 44, 45, and 47, and the left superior temporal gyrus. In GP versus NGP sentences, there was greater activity in the left BAs 44, 45, and 46 extending to the left anterior insula, the pre-supplementary motor area, and the right cerebellum. In the left GFi, verbal working memory activity was located more dorsally (BA 44/45), semantic processing was located more ventrally (BA 47), and syntactic processing was located in between (BA 45). These findings indicate a close relationship between semantic and syntactic processes, and suggest that BA 45 might link verbal working memory and semantic processing via syntactic unification processes.


What Is the Role of the Bacterium Propionibacterium acnes in Type 1 Modic Changes? A Review of the Literature.
This review presents a summary of the pathology and epidemiology of Modic changes and the possible role of Propionibacterium acnes. This information is followed by a synthesis of the most recent clinical research involved in culturing the discs of patients with degenerative disc disease for the presence of bacteria. We also discuss a randomized controlled trial that investigates the effects of antibiotics on patients with chronic low back pain and type 1 Modic changes. We conclude with a brief discussion of the difficulties involved in this research and the significance of the findings.


Caveolin-3 prevents swelling-induced membrane damage via regulation of ICl,swell activity.
Caveola membrane structures harbor mechanosensitive chloride channels (MCCs; including chloride channel 2, chloride channel 3, and SWELL1, also known as LRRC8A) that form a swelling-activated chloride current (ICl,swell) and play an important role in cell volume regulation and mechanoelectrical signal transduction. However, the role of the muscle-specific caveolar scaffolding protein caveolin-3 (Cav3) in regulation of MCC expression, activity, and contribution to membrane integrity in response to mechanical stress remains unclear. Here we showed that Cav3-transfected (Cav3-positive) HEK293 cells were significantly resistant to extreme (<20 milliosmole) hypotonic swelling compared with native (Cav3-negative) HEK293 cells; the percentage of cells with membrane damage decreased from 45% in Cav3-negative cells to 17% in Cav3-positive cells (p < 0.05). This mechanoprotection was significantly reduced (p < 0.05) when cells were exposed to the ICl,swell-selective inhibitor 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid (10 μM). These results were recapitulated in isolated mouse ventricular myocytes, where the percentage of cardiomyocytes with membrane damage increased from 47% in control cells to 78% in 4-[(2-butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid-treated cells (p < 0.05). A higher resistance to hypotonic swelling in Cav3-positive HEK293 cells was accompanied by a significant twofold increase of ICl,swell current density and SWELL1 protein expression, whereas ClC-2/3 protein levels remained unchanged. Förster resonance energy transfer analysis showed a less than 10-nm membrane and intracellular association between Cav3 and SWELL1. Cav3/SWELL1 membrane Förster resonance energy transfer efficiency was halved in mild (220 milliosmole) hypotonic solution as well as after disruption of caveola structures via cholesterol depletion by 1-h treatment with 10 mM methyl-β-cyclodextrin. A close association between Cav3 and SWELL1 was confirmed by co-immunoprecipitation analysis. Our findings indicate that, in the MCCs tested, SWELL1 abundance and activity are regulated by Cav3 and that their association relies on membrane tension and caveola integrity. This study highlights the mechanoprotective role of Cav3, which is facilitated by complimentary SWELL1 expression and activity.


Unusual costochondral bone graft complication.
In hemifacial microsomia, patients with severely hypoplastic mandibles (Pruzansky type III) require replacement of the ramus and condyle unit. Common complications of this procedure include graft fracture and overgrowth of the graft. An uncommon case of osteolysis of the costochondral graft with osteitis of the middle cranial fossa is reported herein. To our knowledge, no such case has been reported in the literature previously. The aim of this report is to present the only known case and to discuss the contributing factors.


Selective increase of cardiac neuronal sympathetic tone: a catheter-based access to modulate left ventricular contractility.
This study was designed to develop a technique to selectively increase the sympathetic tone to the heart by cardiac sympathetic nerve stimulation (SNS). Access to the cardiac sympathetic neurons may allow modulating the adrenergic tone of the heart while avoiding systemic side effects. Cardiac sympathetic nerves course within neural sleeves along the subclavian artery. Because of this proximity, transvascular SNS was attempted with electrode catheters inside the subclavian artery in 16 pigs. Right/left (R-/L-) SNS (20 Hz) during ventricular pacing at 200/min evoked a >100% increase of left ventricular systolic pressure (baseline: 51 +/- 1 mm Hg; L-SNS: 118 +/- 26 mm Hg; R-SNS: 116 +/- 33 mm Hg; p < 0.001) while systemic vascular resistance remained unchanged. There was a sigmoid dose-response curve with rapid on- and offset of the effect during SNS initiation/cessation. Positive inotropic effects persisted for 12 h of continued SNS (n = 4). Besides positive dromotropic effects, L-SNS/R-SNS yielded a 41% and 77% sinus rate increase, respectively. The neural adrenergic tone to the heart can be selectively increased by catheter stimulation of cardiac efferent sympathetic nerves.


In established atherosclerosis, P2Y12 inhibitor vs. aspirin monotherapy reduces MI but not stroke or mortality.
Chiarito M, Sanz-Sánchez J, Cannata F, et al. Monotherapy with a P2Y12 inhibitor or aspirin for secondary prevention in patients with established atherosclerosis: a systematic review and meta-analysis. Lancet. 2020;395;1487-95. 32386592.


[Protect intercellular communication of pigment epithelium after laser photocoagulation].
To observe the protective effect on the intercellular communication of retinal pigment epithelial (RPE) cells of dexamethasone (Dex) and verapamil (Ver) at different concentrations after laser photocoagulation. Ten pig eyes were used to culture pig pigment epithelium cells. Use different concentrations of Dex and Ver to incubate cultured RPE cells 2 hours before laser coagulation, and then measure the intercellular communication function of confluent cells surrounding the coagulation spots after photocoagulation. 125 mg/L Dex and 20 mg/L Ver could protect the intercellular communication of RPE cells under laser photocoagulation. The high concentration of drugs had better result. Both Dex and Ver can preserve the intercellular communication in vitro. The protective capacity is related to the concentration of drug.


Modeling and optimization of the spray drying parameters for soapwort (Gypsophila Sp.) extract.
In this study, the effects of spray drying parameters as feed soluble solid content, inlet air temperature and outlet air temperature on spray drying of soapwort (Gypsophila arrostii) extract have been examined. Central composite design was used with 15-30 °Bx, 110-160 °C and 50-80 °C for feed soluble solid content, inlet air temperature and outlet air temperature, respectively. Moisture content, water activity, tapped density, total saponin content and foam volume of the obtained powders were measured as responses of the experimental plan. The spray drying parameters were optimized by considering saponin content and foam volume by response surface methodology. According to the numerical optimization, optimum feed soluble solid content, inlet and outlet air temperatures were 15 °Bx, 160 °C and 67 °C respectively with a desirability factor of 0.822. After verification at optimum conditions, the error percentages were found to be 5.96% and 2.15% for saponin content and foam volume respectively.


Serum copper and zinc concentration in premature and small-for-date infants.
Serum copper (Cu) and zinc (Zn) concentrations were measured in neonates with an appropriate birth weight for gestational age (AGA) and in small-for-gestational age infants. At 7 days of age, there was a positive correlation between serum Cu concentration and gestational age (GA) (r = 0.63; P < 0.001) and a negative correlation between Zn concentration and GA (r = 0.62; P < 0.01). At 7 days of age, the mean (+/- S.E.) concentrations in AGA full-term infants (Cu, 79 +/- 8 microgram/dl; Zn, 84 +/- 4) were similar to those in small-for-gestational age, full-term infants (Cu, 78 +/- 6 microgram/dl; Zn, 85 +/- 12). In preterm infants, there was also no difference between AGA and small-for-gestational age infants. In 23 AGA infants with a birth weight of less than 1500 g, serum Cu concentration increased from 51 +/- 7 microgram/dl at the age of 7 days to 86 +/- 7 microgram/dl at the age of 60 days (paired t-test: P < 0.05) whereas serum Zn concentration decreased from 149 +/- 9 to 91 +/- 5 microgram/dl (P < 0.01). A positive correlation was found between serum Zn concentration and daily intake of Zn (n = 39; r = 0.3458; P < 0.05), but no correlation was found for serum Cu concentration. The evolution of serum Cu and Zn concentration with total age (GA + postnatal age) in the infants with a low birth weight (i.e., < 1500 g) was similar to the evolution with GA.


Evaluating study designs and treatment outcomes of antidepressant pharmacogenetic clinical trials - Challenges and future perspectives. A critical review.
Several data indicate that the success of pharmacological treatment in major depressive disorder (MDD) is still unsatisfactory. The reasons for the low response and remission rates are multiple and depend on environmental and biological factors intrinsic to the disease and drug treatments. Pharmacogenetic (PG) tests have the potential to increase efficacy predicting outcome and to reduce antidepressant discontinuation due to side effects. Several studies investigated the utility of PG tests for antidepressants in MDD with interesting but contrasting results. To date most of them are observational studies with no comparator group, and few are randomized controlled trials (RCTs). The aim of this review is to provide an evaluation of the state of art on clinical methodologic features of RCTs with PG tests for antidepressant drugs in MDD, offering suggestions and favoring new insights that could be useful in the implementation of future trials. Several limitations concerning study design, generalization of results, duration of trials, patients group studied, and cost-effectiveness ratio were found, and a number of barriers have been noted in the adoption of PG tests into clinical practice. Despite some preliminary positive results, there is the need for larger and longer-term RCT studies, with the goal to capture the real impact of PG tests, also with stratified analysis concerning MDD features in terms of severity and antidepressant treatment failures in different ethnicity cohorts.


The alternatively spliced LRRFIP1 Isoform-1 is a key regulator of the Wnt/β-catenin transcription pathway.
The GC-rich Binding Factor 2/Leucine Rich Repeat in the Flightless 1 Interaction Protein 1 gene (GCF2/LRRFIP1) is predicted to be alternatively spliced in five different isoforms. Although important peptide sequence differences are expected to result from this alternative splicing, to date, only the gene transcription regulator properties of LRRFIP1-Iso5 were unveiled. Based on molecular, cellular and biochemical data, we show here that the five isoforms define two molecular entities with different expression profiles in human tissues, subcellular localizations, oligomerization properties and transcription enhancer properties of the canonical Wnt pathway. We demonstrated that LRRFIP1-Iso3, -4 and -5, which share over 80% sequence identity, are primarily located in the cell cytoplasm and form homo and hetero-multimers between each other. In contrast, LRRFIP1-Iso1 and -2 are primarily located in the cell nucleus in part thanks to their shared C-terminal domain. Furthermore, we showed that LRRFIP1-Iso1 is preferentially expressed in the myocardium and skeletal muscle. Using the in vitro Topflash reporter assay we revealed that among LRRFIP1 isoforms, LRRFIP1-Iso1 is the strongest enhancer of the β-catenin Wnt canonical transcription pathway thanks to a specific N-terminal domain harboring two critical tryptophan residues (W76, 82). In addition, we showed that the Wnt enhancer properties of LRRFIP1-Iso1 depend on its homo-dimerisation which is governed by its specific coiled coil domain. Together our study identified LRRFIP1-Iso1 as a critical regulator of the Wnt canonical pathway with a potential role in myocyte differentiation and myogenesis.


[Identification and identity formation in individual psychotherapy in schizophrenia].
Transference as well as counter transference is necessary within the therapy of neuroses; but with the relation between doctor and patient in psyotherapy certain components form processes of identification and counter identification between those two partners of the therapeutic event. Way, meaning and form of these processes leading to a new creation of identity in the patient are discussed in the following study. The nature of psychotherapy of schizophrenia as well as some theoretical aspects are lightened.


Enlarging intratracheal tube cuff diameter: a quantitative roentgenographic study of its value in the early prediction of serious tracheal damage.
A prospective study to radiographically document impending tracheal damage in patients on continuous mechanical ventilation was done in 135 intubated adult patients over an eighteen month period. The previously unrecognized enlarging cuff/trachea ratio over 150% was seen in 18 patients. Five of 9 patients who died with C/T ratio over 150% were autopsied; all had severe tracheal damage at the cuff site. Four of 5 patients who were decannulated/extubated developed tracheal stenosis at the cuff site, necessitating tracheal resection in 3 patients. Thus a C/T ratio over 150% is a reliable clinical indicator of tracheal damage. Some thoughts as to prevention of this iatrogenic disease are presented.


RNA-Seq reveals ACTH-induced steroid hormone pathway participating in goat adrenal gland response to castration.
The content of androgen from adrenal is elevated under castration, and the mechanisms of compensatory secretion of adrenal androgen remain unknown. This study was designed to compare the transcript profiles between adrenals from noncastrated, orchiectomized and immunocastrated Yiling goats. Fifteen goats were randomly divided into three groups: pVAX-asd injection (control) group, pVAX-B2L-(G4S)3-kisspeptin-54-asd immunization (PBK-asd) group, and surgical castration (SC) group. Subsequently, serum was collected every two weeks after the initial immunization for hormone assays. At week 14 after immunization, adrenal glands were collected for transcriptome sequencing and qPCR. Serum testosterone concentration was significantly reduced in PBK-asd and SC group, demonstrating the effectiveness of castration. Both surgical and immunized castration resulted in adrenal hyperplasia, and thickness of adrenal cortex elevated. The specific genes involving castration were enriched in many pathways, including Steroid hormone biosynthesis pathway. The adrenocorticotropic hormone (ACTH), which promotes the production of adrenal steroids, and dehydroepiandrosterone (DHEA), a steroid hormone secreted by adrenal glands, both increased after castration. Further construction of co-expression network for transcription genes and traits (including adrenal weight and cortex thickness, ACTH and DHEA concentration) showed that the trait-related genes were enriched in multiple steroid-related pathways. These results showed that adrenal compensatory hyperplasia and androgen secretion caused by castration may involve in ACTH-induced steroid hormone synthesis.


A role for glucose and insulin preprandial profiles to differentiate meals and snacks.
A physiological distinction between eating occasions may help account for contradictory findings on the role of eating frequency in energy homeostasis. We assessed this issue using a midafternoon eating occasion known in France as the goûter that often consists of snack foods. Among the 24 male subjects, 8 habitually consumed four meals per day, i.e., were usual goûter eaters (GE) and 16 habitually took 3 meals per day, i.e., usual non-goûter non-snack eaters (NGNSE). All subjects were time blinded from lunchtime and had to request subsequent meals. Blood was continuously withdrawn and collected with a change of tube every 10 min until dinner request. During the session, 8 of the non-goûter eaters (NGE) were offered a snack 210 min after lunch and were designated as non-goûter snack eaters (NGSE) if they ate. Results showed that the goûter was preceded by high hunger scores and a linear decline in plasma glucose (-9.0+/-3.0%, P<.05) and insulin concentrations (-22.9+/-6.0%, P<.05). These profiles were not observed before the snack. The dinner of GE was requested later and was smaller compared to NGNSE, whereas the snack altered neither time of request nor energy intake (EI) at dinner. Among blood variables, leptin at the onset of eating was the only factor that was predictive of both intermeal interval and EI. The glucose and insulin profiles indicate that snacks should not be considered as meals in studies on the role of eating frequency in energy homeostasis.


Success of repeat ERCP by the same endoscopist.
The success rate of repeat endoscopic retrograde cholangiopancreatography (ERCP) by the same endoscopist after a failed initial attempt is unknown. It has been suggested that a repeat examination at a tertiary referral center be performed after an unsuccessful attempt. Our aim was to determine the success rate of repeat ERCP at a different endoscopic session by the same endoscopist and the outcomes among patients with a failed index procedure. A review of 500 consecutive ERCP procedures was performed at a teaching institution. The overall initial success rate for cannulation of the duct of interest was 90.8% at index endoscopy. Endoscopy was repeated after 51% unsuccessful procedures, and access to the desired duct was achieved in 87.5% of repeat attempts. A needle knife was used in 21% instances, and its use facilitated cannulation of the duct of interest in 80%. No complications occurred with repeat ERCP. Of the 3 patients who underwent failed repeated ERCP, 1 was not available for the follow-up study, 1 had metastatic cancer, and the other had pancreas divisum. The outcomes among patients who did not undergo repeat ERCP included malignant disease diagnosed with other imaging techniques (35% of patients) and no further admissions or emergency room visits for suspected pancreaticobiliary symptoms (39% of patients). Repeat ERCP by the same endoscopist yields an 87.5% success rate. This leads to an overall success rate of 95%.


PDZ domain-binding motif of human T-cell leukemia virus type 1 Tax oncoprotein is essential for the interleukin 2 independent growth induction of a T-cell line.
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic agent of adult T-cell leukemia (ATL), whereas HTLV type 2 (HTLV-2), is not associated with ATL or any other leukemia. HTLV-1 encodes the transforming gene tax1, whose expression in an interleukin (IL)-2-dependent T-cell line (CTLL-2) induces IL-2-independent growth. In this study, we demonstrated that IL-2-independent growth induction by Tax1 was abrogated by mutations of the PDZ domain-binding motif (PBM) at the Tax1 C-terminus. HTLV-2 Tax2, which shares 75% amino acid identity with Tax1 but does not have a PBM, was not able to induce IL-2-independent growth of CTLL-2. Our results suggest that Tax1, through interaction with PDZ domain protein(s) induces IL-2-independent growth, which may be a factor in multi-step leukemogenesis caused by HTLV-1.


Inhibition of guanylate cyclases by methylxanthines and papaverine.
The inhibition of guanylate cyclase activity by theophylline, methylisobutylxanthine, and papaverine has been studied with partially purified soluble and particulate enzyme preparations from rat organs. An excess of unlabeled cGMP has been used in the assays to eliminate significant further metabolism of the radioactive cGMP formed from [alpha-32P]GTP. All of the guanylate cyclases examined were significantly inhibited by millimolar concentrations of theophylline and papaverine. Inhibition of soluble liver guanylate cyclase by theophylline was competitive with respect to GTP while inhibition by papaverine was noncompetitive. Thus, some drugs which are often used as inhibitors of cyclic nucleotide phosphodiesterases can inhibit guanylate cyclases as well.


Is a 12-h Nitrox dive hazardous for pulmonary function?
Prolonged exposure to a high partial pressure of oxygen leads to inflammation of pulmonary tissue [pulmonary oxygen toxicity (POT)], which is associated with tracheobronchial irritation, retrosternal pain and coughing, and decreases in vital capacity (VC). The nitric oxide (NO) concentration in exhaled gas (FeNO) has been used as an indicator of POT, but the effect of SCUBA diving on FeNO has rarely been studied. The study presented here aimed to assess alterations to pulmonary function and FeNO following a 12-h dive using breathing apparatus with a relatively high partial pressure of oxygen. Six healthy, male, non-smoking military SCUBA divers were recruited (age 31.8 ± 2.7 years, height 179 ± 0.09 cm, and body weight 84.6 ± 14 kg). Each diver completed a 12-h dive using a demand-controlled semi-closed-circuit rebreather. During the 12 h of immersion, divers were subjected to 672 oxygen toxicity units (OTU). A complete pulmonary function test (PFT) was completed the day before and immediately after immersion. FeNO was measured using a Nobreath™ Quark (COSMED™, Rome, Italy), three times for each diver. The first datapoint was collected before the dive to establish the "basal state", a second was collected immediately after divers emerged from the water, and the final measurement was taken 24 h after the dive. Despite prolonged inhalation of a hyperoxic hyperbaric gas mixture, no clinical pulmonary symptoms were observed, and no major changes in pulmonary function were detected. However, a major decrease in FeNO values was observed immediately after emersion [0-12 ppb (median, 3.8 ppb)], with a return to baseline [2-60 ppb (median, 26 ppb) 24 h later (3-73 ppb (median, 24.7 ppb)]. These results suggest that if the OTU remain below the recommended limit values, but does alter FeNO, this type of dive does not persistently impair lung function.