The tumour necrosis factor-α-238A allele increases the risk of chronic HBV infection in European populations.
Tumour necrosis factor-α (TNF-α) plays a pivotal role in viral clearance and host immune response to hepatitis B virus (HBV) infection, of which the production capacity in individuals is demonstrated to be influenced by a single nucleotide polymorphism within the promoter region of TNF-α genes. However, there have been conflicting results reported in previous studies on TNF-α-238 and TNF-α-863 gene promoter polymorphisms in chronic HBV infection. To derive a more precise estimation of their relationship, we searched Pubmed (January, 1966-August, 2010) and China Biological Medicine Database (January, 1978-August, 2010) and carried out a meta-analysis involving nineteen studies that included 5245 chronic HBV infection cases and 3181 controls describing G238A genotypes, and eleven studies totalling 3576 cases and 2044 controls describing C863A genotypes. The overall meta-analysis did not suggest significant associations of TNF-α-238 and TNF-α-863 gene promoter polymorphisms with chronic HBV infection. However, in subgroup analysis by ethnicity, it indicated that TNF-α-238A allele carriers (GA + AA) in European populations had an increased risk of developing chronic HBV infection (OR = 2.22, 95% CI: 1.07-4.58, P = 0.032; OR = 4.46, 95% CI: 1.75-11.38, P = 0.002, respectively), when compared with spontaneous recovered and healthy populations, respectively. However, no significant associations were found in Asian populations in all genetic models. So, we draw the conclusion that the TNF-α-238A allele may increase the risk of chronic HBV infection in European populations.


Experimental retinal detachment causes widespread and multilayered degeneration in rabbit retina.
Retinal detachment remains one of the most frequent causes of visual impairment in humans, even after ophthalmoscopically successful retinal reattachment. This study was aimed at monitoring (ultra-) structural alterations of retinae of rabbits after experimental detachment. A surgical procedure was used to produce local retinal detachments in rabbit eyes similar to the typical lesions in human patients. At various periods after detachment, the detached retinal area as well as neighbouring attached regions were studied by light and electron microscopy. In addition to the well-known degeneration of photoreceptor cells in the detached retina, the following progressive alterations were observed, (i) in both the detached and the attached regions, an incomplete but severe loss of ganglion cell axons occurs; (ii) there is considerable ganglion cell death, particularly in the detached area; (iii) even in the attached retina distant from the detachment, small adherent groups of photoreceptor cells degenerate; (iv) these photoreceptor cells degenerate in an atypical sequence, with severely destructed somata and inner segments but well-maintained outer segments; and (v) the severe loss of retinal neurons is not accompanied by any significant loss of Müller (glial) cells. It is noteworthy that the described progressive (and probably irreparable) retinal destructions occur also in the attached retina, and may account for visual impairment in strikingly large areas of the visual field, even after retinal reattachment.


Carcinoembryonic antigen-related cell adhesion molecule 1: a key regulatory protein involved in leiomyoma growth.
To assess and characterize the role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in the development of uterine leiomyoma. Laboratory study. Academic research center. Not applicable. Laboratory investigation. In vitro assessment of human leiomyoma and myometrial tissue specimens as well as immortalized leiomyoma and myometrial cell lines. Western blotting and immunohistochemical analyses were performed to assess differences in CEACAM1 content between leiomyoma and myometrial samples. Small interfering RNA silencing experiments and transient transfection experiments were performed to characterize the regulatory role of CEACAM1 on downstream signaling cascades. Analysis of RNA sequencing data revealed decreased CEACAM1 expression in human uterine leiomyoma specimens compared with that in myometrial samples. This translated to a significant down-regulation in CEACAM1 protein content in human leiomyoma compared with patient-matched myometrial tissue samples (0.236 ± 0.05-fold). A similar decrease in CEACAM1 protein content was observed in matched immortalized leiomyoma cell (ILC) and immortalized myometrial cell lines (0.21 ± 0.07). Immunohistochemical analysis revealed decreased staining intensity in leiomyoma surgical specimens compared with the matched myometrium of placebo patients. Lower CEACAM1 levels in leiomyoma were associated with increased activation of both the mitogen-activated protein kinase (MAPK) and the phosphoinositide 3-kinase/protein kinase B pathways compared with that in myometrial cells. This is significant because activation of these pathways plays an important role in leiomyoma growth. Treatment of myometrial cells with CEACAM1 small interfering RNA resulted in a significant down-regulation of CEACAM1 at the protein level (0.272 ± 0.06-fold) and was associated with increased activation of the MAPK (1.62 ± 0.21-fold) and phosphoinositide 3-kinase/protein kinase B (1.79 ± 0.35-fold) pathways, as well as increased collagen production (2.1 ± 0.49-fold). Rescue of CEACAM1 expression in leiomyoma cells by transient transfection restored regulatory control and resulted in lower activation of the MAPK pathway (0.58 ± 0.37-fold). CEACAM1 is an important protein involved in regulating many signal transduction pathways. Decreased CEACAM1 expression in leiomyoma allows permissive uncontrolled overactivation and up-regulation of downstream pathways that may contribute to leiomyoma growth.


Invariance of object detection in untrained deep neural networks.
The ability to perceive visual objects with various types of transformations, such as rotation, translation, and scaling, is crucial for consistent object recognition. In machine learning, invariant object detection for a network is often implemented by augmentation with a massive number of training images, but the mechanism of invariant object detection in biological brains-how invariance arises initially and whether it requires visual experience-remains elusive. Here, using a model neural network of the hierarchical visual pathway of the brain, we show that invariance of object detection can emerge spontaneously in the complete absence of learning. First, we found that units selective to a particular object class arise in randomly initialized networks even before visual training. Intriguingly, these units show robust tuning to images of each object class under a wide range of image transformation types, such as viewpoint rotation. We confirmed that this "innate" invariance of object selectivity enables untrained networks to perform an object-detection task robustly, even with images that have been significantly modulated. Our computational model predicts that invariant object tuning originates from combinations of non-invariant units via random feedforward projections, and we confirmed that the predicted profile of feedforward projections is observed in untrained networks. Our results suggest that invariance of object detection is an innate characteristic that can emerge spontaneously in random feedforward networks.


Creatine supplementation for weak muscles in persons with chronic tetraplegia: a randomized double-blind placebo-controlled crossover trial.
Creatine supplementation improves muscle strength in some patient populations with neurologic disorders. The purpose of this study was to determine whether creatine supplementation improves muscle strength and endurance in weak upper limb muscles in persons with tetraplegia, and whether it improves function. Outpatients with tetraplegia and mild wrist extensor weakness were randomized to receive either creatine or placebo in a double-blind crossover design. During creatine supplementation, participants were loaded with 10 g orally twice per day for 6 days, then maintained on 5 g daily until undergoing testing. Main outcome measures, performed at baseline, after placebo, and after creatine supplementation, included maximal voluntary wrist extensor isometric contraction strength (MVC), endurance times for 5 submaximal wrist extensor contractions, and the Grasp and Release Test for hand function. Eight individuals (7 men, 1 woman) with tetraplegia met inclusion criteria and completed all study phases. The mean age of participants was 48 years, and 7 of 8 had C6 motor level injuries. There were no significant differences in MVC, endurance times, or hand function for creatine vs placebo. Creatine does not improve MVC and endurance of weak wrist extensors and does not improve hand function in individuals with tetraplegia.


Expression of osteoprotegerin and osteoprotegerin ligand in giant cell tumor of bone and its clinical significance.
In this study, we used a substance P (SP) immunohistochemical method to analyze the expression localization of osteoprotegerin (OPG) and osteoprotegerin ligand (OPGL) in giant cell tumor (GCT) of the bone, and to detect the clinical significance of their expression. The data showed that the positive expression rate of OPG in the multinucleated giant cells (MGCs) and stromal cells (STCs) of GCT was 80.65 and 74.19%, respectively. The positive expression rate of OPG in MGCs was correlated with age and prognosis (P<0.05), but not in STCs. The strength of positive OPG expression in MGCs and STCs was negatively correlated with prognosis (rs=-0.397, P<0.05; rs=-0.390, P<0.05, respectively). The positive expression rate of OPGL in the MGCs and STCs was 41.94 and 67.74%, respectively. The positive expression rate of OPGL in the MGCs was correlated with age and prognosis (P<0.05); the strength of OPGL expression in MGCs was positively correlated with Campanicci's grade and recurrence. Additionally, the positive expression rate of OPGL in STCs was correlated with age and Jaffe's grade (P<0.05). The strength of OPGL expression in STCs was negatively correlated with Jaffe's grade (rs=-0.534, P<0.05). In conclusion, OPG and OPGL are expressed in MGCs and STCs in GCT of the bone. The invasion of tumor cells was positively correlated with OPGL in MGCs, which confirmed that MGCs participate in the process of osteolytic destruction of GCT of bone.


Cell therapy for multiple sclerosis.
The spontaneous recovery observed in the early stages of multiple sclerosis (MS) is substituted with a later progressive course and failure of endogenous processes of repair and remyelination. Although this is the basic rationale for cell therapy, it is not clear yet to what degree the MS brain is amenable for repair and whether cell therapy has an advantage in comparison to other strategies to enhance endogenous remyelination. Central to the promise of stem cell therapy is the therapeutic plasticity, by which neural precursors can replace damaged oligodendrocytes and myelin, and also effectively attenuate the autoimmune process in a local, nonsystemic manner to protect brain cells from further injury, as well as facilitate the intrinsic capacity of the brain for recovery. These fundamental immunomodulatory and neurotrophic properties are shared by stem cells of different sources. By using different routes of delivery, cells may target both affected white matter tracts and the perivascular niche where the trafficking of immune cells occur. It is unclear yet whether the therapeutic properties of transplanted cells are maintained with the duration of time. The application of neural stem cell therapy (derived from fetal brain or from human embryonic stem cells) will be realized once their purification, mass generation, and safety are guaranteed. However, previous clinical experience with bone marrow stromal (mesenchymal) stem cells and the relative easy expansion of autologous cells have opened the way to their experimental application in MS. An initial clinical trial has established the probable safety of their intravenous and intrathecal delivery. Short-term follow-up observed immunomodulatory effects and clinical benefit justifying further clinical trials.


Structured modelling of animal cells.
Recent advances in computer technology have promoted the design and use of detailed, computer-based models for biological systems. For many non-biological systems, the complexity of such simulations may be considered inappropriate and unwieldy, but in biological systems, and more specifically in animal cell culture, this level of complexity simply mimics what is only beginning to be understood about metabolic processs. With this in mind, we contend that complex, structured models are vital tools in the investigation of fundamental biological processes. An example of such a simulation, which describes the commercial production of therapeutic proteins by animal cell cultures, is considered.


Toll-like receptor-4 deficiency attenuates doxorubicin-induced cardiomyopathy in mice.
Cardiac inflammation and generation of oxidative stress are known to contribute to doxorubicin (Dox)-induced cardiomyopathy. Toll-like receptors (TLRs) are a part of the innate immune system and are involved in cardiac stress reactions. Since TLR4 might play a relevant role in cardiac inflammatory signalling, we investigated whether or not TLR4 is involved in Dox-induced cardiotoxicity. Five days after a single injection of Dox (20 mg/kg; i.p.), left ventricular pressure-volume loops were measured in wild-type and TLR4-deficient mice (TLR4-/-) Dox-treated and control mice. Analyses of possible pathophysiological mechanisms were performed in left ventricular tissue and isolated myocytes, respectively. Dox injection resulted in an impairment of left ventricular function and neurohumoral activation, indexed by increased ET-1 expression. This was further associated with an increase in cardiac oxidative stress, inflammation and apoptosis, as indicated by an up-regulation of cardiac lipid peroxidation, TNF-alpha expression and enhanced content of TUNEL-positive cells. In contrast, TLR4-/- Dox mice showed improved left ventricular function with reduced oxidative and inflammatory stress response including reduced cardiac apoptosis. These results were found to be associated with an increase of GATA-4 expression. TLR4 deficiency improves left ventricular function and attenuates pathophysiological key mechanisms in Dox-induced cardiomyopathy.


Stepwise effects of the BCR sequential chemical extraction procedure on dissolution and metal release from common ferromagnesian clay minerals: a combined solution chemistry and X-ray powder diffraction study.
Sequential extraction procedures (SEPs) are commonly used to determine speciation of trace metals in soils and sediments. However, the non-selectivity of reagents for targeted phases has remained a lingering concern. Furthermore, potentially reactive phases such as phyllosilicate clay minerals often contain trace metals in structural sites, and their reactivity has not been quantified. Accordingly, the objective of this study is to analyze the behavior of trace metal-bearing clay minerals exposed to the revised BCR 3-step plus aqua regia SEP. Mineral quantification based on stoichiometric analysis and quantitative powder X-ray diffraction (XRD) documents progressive dissolution of chlorite (CCa-2 ripidolite) and two varieties of smectite (SapCa-2 saponite and SWa-1 nontronite) during steps 1-3 of the BCR procedure. In total, 8 (+/-1) % of ripidolite, 19 (+/-1) % of saponite, and 19 (+/-3) % of nontronite (% mineral mass) dissolved during extractions assumed by many researchers to release trace metals from exchange sites, carbonates, hydroxides, sulfides and organic matter. For all three reference clays, release of Ni into solution is correlated with clay dissolution. Hydrolysis of relatively weak Mg-O bonds (362 kJ/mol) during all stages, reduction of Fe(III) during hydroxylamine hydrochloride extraction and oxidation of Fe(II) during hydrogen peroxide extraction are the main reasons for clay mineral dissolution. These findings underscore the need for precise mineral quantification when using SEPs to understand the origin/partitioning of trace metals with solid phases.


Effect of cysteine desulfhydrase gene disruption on L-cysteine overproduction in Escherichia coli.
In Escherichia coli, the enzyme called cysteine desulfhydrase (CD), which is responsible for L-cysteine degradation, was investigated by native-PAGE and CD activity staining of crude cell extracts. Analyses with gene-disrupted mutants showed that CD activity resulted from two enzymes: tryptophanase (TNase) encoded by tnaA and cystathionine beta-lyase (CBL) encoded by metC. It was also found that TNase synthesis was induced by the presence of L-cysteine. The tnaA and metC mutants transformed with the plasmid containing the gene for feedback-insensitive serine acetyltransferase exhibited higher L-cysteine productivity than the wild-type strain carrying the same plasmid. These results indicated that TNase and CBL did act on L-cysteine degradation in E. coli cells.


Nerve growth factor (NGF) receptor on rat glial cell lines. Evidence for NGF internalization via p75NGFR.
Two types of nerve growth factor (NGF) receptors have been described: high affinity (class I) and low affinity (class II). Biological responses to NGF are thought to be mediated by class I receptors, whereas the role of class II receptors is less clear. While some neuronal cells express both receptor types, only class II receptors have been detected on glial cells. Two glial cell lines, peripheral Schwannoma D6P2T and central 33B glioma cells, were employed to investigate the properties of class II receptors in the absence of class I receptors. These cell lines were found to express NGF receptors identified as class II by a low nanomolar dissociation constant, rapid dissociation kinetics at 4 degrees C, and trypsin sensitivity. The receptor was found to bind brain-derived neurotrophic factor with similar affinity as NGF. The responsible binding molecule appeared in sodium dodecyl sulfate-polyacrylamide gel electrophoresis as a heterogeneously glycosylated protein of 60-80 kDa with a tendency to aggregate. All receptor bands affinity-labeled with radioiodinated NGF were immunoprecipitated with anti-p75NGFR antibody, but not with anti-p140prototrk antiserum. In these cells, which express p75NGFR as only NGF receptor, a time- and temperature-dependent appearance of a nondisplaceable, trypsin-resistant, acid wash-stable ligand fraction, followed by an increase of trichloroacetic acid-soluble radiolabel in the medium was observed. This sequestration resembled receptor-mediated internalization with subsequent degradation of NGF. Whether this ligand processing indicates a functional role of p75NGFR in glial cells remains to be shown.


Effects of growth hormone therapeutic supplementation on hematopoietic stem/progenitor cells in children with growth hormone deficiency: focus on proliferation and differentiation capabilities.
We investigated the direct effects of growth hormone (GH) replacement therapy (GH-RT) on hematopoiesis in children with GH deficiency (GHD) with the special emphasis on proliferation and cell cycle regulation. Peripheral blood (PB) was collected from sixty control individuals and forty GHD children before GH-RT and in 3rd and 6th month of GH-RT to measure hematological parameters and isolate CD34(+)-enriched hematopoietic progenitor cells (HPCs). Selected parameters of PB were analyzed by hematological analyzer. Moreover, collected HPCs were used to analyze GH receptor (GHR) and IGF1 expression, clonogenicity, and cell cycle activity. Finally, global gene expression profile of collected HPCs was analyzed using genome-wide RNA microarrays. GHD resulted in a decrease in several hematological parameters related to RBCs and significantly diminished clonogenicity of erythroid progenies. In contrast, GH-RT stimulated increases in clonogenic growth of erythroid lineage and RBC counts as well as significant up-regulation of cell cycle-propagating genes, including MAP2K1, cyclins D1/E1, PCNA, and IGF1. Likewise, GH-RT significantly modified GHR expression in isolated HPCs and augmented systemic IGF1 levels. Global gene expression analysis revealed significantly higher expression of genes associated with cell cycle, proliferation, and differentiation in HPCs from GH-treated subjects. (i) GH-RT significantly augments cell cycle progression in HPCs and increases clonogenicity of erythroid progenitors; (ii) GHR expression in HPCs is modulated by GH status; (iii) molecular mechanisms by which GH influences hematopoiesis might provide a basis for designing therapeutic interventions for hematological complications related to GHD.


Outer-Sphere Tyrosine 159 within the 3-Mercaptopropionic Acid Dioxygenase S-H-Y Motif Gates Substrate-Coordination Denticity at the Non-Heme Iron Active Site.
Thiol dioxygenases are non-heme mononuclear iron enzymes that catalyze the O2-dependent oxidation of free thiols (-SH) to produce the corresponding sulfinic acid (-SO2-). Regardless of the phylogenic domain, the active site for this enzyme class is typically comprised of two major features: (1) a mononuclear ferrous iron coordinated by three protein-derived histidines and (2) a conserved sequence of outer Fe-coordination-sphere amino acids (Ser-His-Tyr) spatially adjacent to the iron site (∼3 Å). Here, we utilize a promiscuous 3-mercaptopropionic acid dioxygenase cloned from Azotobacter vinelandii (Av MDO) to explore the function of the conserved S-H-Y motif. This enzyme exhibits activity with 3-mercaptopropionic acid (3mpa), l-cysteine (cys), as well as several other thiol-bearing substrates, thus making it an ideal system to study the influence of residues within the highly conserved S-H-Y motif (H157 and Y159) on substrate specificity and reactivity. The pKa values for these residues were determined by pH-dependent steady-state kinetics, and their assignments verified by comparison to H157N and Y159F variants. Complementary electron paramagnetic resonance and Mössbauer studies demonstrate a network of hydrogen bonds connecting H157-Y159 and Fe-bound ligands within the enzymatic Fe site. Crucially, these experiments suggest that the hydroxyl group of Y159 hydrogen bonds to Fe-bound NO and, by extension, Fe-bound oxygen during native catalysis. This interaction alters both the NO binding affinity and rhombicity of the 3mpa-bound iron-nitrosyl site. In addition, Fe coordination of cys is switched from thiolate only to bidentate (thiolate/amine) for the Y159F variant, indicating that perturbations within the S-H-Y proton relay network also influence cys Fe binding denticity.


Neuronal signals are required for estrogen-mediated induction of progesterone receptor in cultured rat Schwann cells.
Rat glial cells from the central nervous system (CNS) and the peripheral nervous system (PNS) express steroid hormone receptors. Whereas progestin receptors (PR) in cultured glial cells of the CNS are estrogen-inducible, similar increase of PR in cultured Schwann cells, the glial cells of the PNS, prepared from newborn rat sciatic nerves, could not be demonstrated. In the present work we have used fetal dorsal root ganglion cultures to study the effect of estrogen and its antagonist ICI 164,384 on the expression of PR in rat Schwann cells. The PR levels were measured by hormone binding in whole cell assays or in cell cytosol, 18 h after excision of the ganglion from the cultures. Treatment of DRG-Schwann cell cultures with estradiol (E2) increased PR levels from about 60 to 160 fmol per mg cytosol protein, in untreated and estrogen-treated cells, respectively. This increase was dose-dependent; maximal induction was obtained at 50 nM E2-concentration. Treatment of the cultures with the antagonist ICI 164,384 completely inhibited the estrogen-induction of PR, whereas ICI alone did not influence receptor levels in Schwann cells. The estrogen-induction of PR was dependent on the presence of dorsal root ganglion during the period of estrogen treatment. Excision of the neuronal mass from the cultures caused a rapid decrease and disappearance of estrogen-inducible progestin receptors, whereas the concentration of non-inducible PR-binding sites remained unchanged. Estradiol had no influence on DRG-Schwann cell proliferation, only replated secondary Schwann cells showed a slightly higher level of proliferation in presence of 100 nM E2 and 5 microM forskolin. Receptors for estrogen (ER) were also demonstrated in DRG-Schwann cells by ligand binding experiments. Specific ER-binding was 36 +/- 8 fmol bound estradiol per mg cytosol protein. Finally, both PR and ER were visualized in Schwann cells by indirect immunofluorescence staining using specific anti-receptor antibodies. These findings suggest that the expression of estrogen-inducible progestin receptors in cultured glial cells of the PNS is mediated via intracellular estrogen receptors and that it requires the presence of neuronal signal(s).


Dietary sugar promotes gene activation in intestinal cell chromatin of adult rats.
The effect of dietary sucrose on transcription activity of chromatin from intestinal cells of adult rats was investigated. Chromatin-bound RNA polymerase II activity was significantly enhanced after feeding sucrose to rats. RNA polymerase II transcribes the genes coding for pre-messenger RNA. The results indicate that feeding of sucrose increased the synthesis of pre-messenger RNA molecules coding for specific proteins which are involved in the adaptive processes of sucrose hydrolysis in intestinal cells.


A systems model approach to the ventilatory anaerobic threshold.
An analogue systems model of whole-body human bioenergetics predicts a change in kinetics of VO2 time series values as a result of exercise levels above an anaerobic threshold. Plotted VO2 results from exercising subjects appear to confirm this change. The purpose of this study is to describe the background to the systems model analogue of the anaerobic threshold and a test procedure devised to estimate this threshold. The estimate so obtained has the dual advantages of being based on model theory and of not being subject to the sort of ambient variations inherent in a single-test determination. A non-homogeneous group of eight subjects comprising a full replicate of a 2(3) factorial experimental design, with factors age, sex and training status, took part in the study. On one hand the results indicate acceptance of the systems model theory. On the other, the analogue threshold measure possesses corresponding properties to the conventional anaerobic threshold. It is higher for trained (155-214 W) than for untrained subjects (108-158 W), higher for males (149-214 W) than for females (108-170 W), and displays no evident interaction effects. Results for the VO2 time constant and for the work efficiency, display similar effects except for an interaction in the latter between age and training status. These experimental findings are regarded as confirmatory of the nature of the analogue threshold measure.


Resistance to Azoxystrobin and Thiophanate-Methyl Is Widespread in Colletotrichum spp. Isolates From the Mid-Atlantic Strawberry Fields.
Multiple Colletotrichum species have been found to be responsible for strawberry anthracnose, and prevalence of each species seems to vary by regions and/or host tissues. In this study, a total of 200 Colletotrichum isolates were obtained from different strawberry cultivars displaying anthracnose symptoms in the mid-Atlantic fields. Analysis of g3pdh, tub2, and/or internal transcribed spacer sequences revealed four Colletotrichum species, including C. nymphaeae, C. fioriniae, C. siamense, and C. lineola. C. nymphaeae was the predominant species, representing 90% of all isolates collected. This species was found from all strawberry organs/tissues examined, whereas C. siamense and C. fioriniae were limited to the crown and fruit, respectively. Further, all Colletotrichum isolates were screened for resistance to azoxystrobin in vitro, and all C. siamense isolates were additionally screened for resistance to thiophanate-methyl. The overall frequency of resistance to azoxystrobin and thiophanate-methyl was 48 and 67%, respectively. G143A in the cytochrome b gene was found in all C. nymphaeae and C. siamense isolates with high level of resistance, with EC50 >100 µg/ml, while F129L was found in two of the five C. nymphaeae isolates with moderate resistance, with EC50 values ranging from 2.6 to 7.8 µg/ml. All C. fioriniae isolates tested were found to be less sensitive to azoxystrobin, with EC50 values ranging from 9.7 to 14.4 µg/ml, despite no mutations detected in the cytochrome b gene. Moreover, E198A in tub2 was linked with C. siamense isolates resistant to thiophanate-methyl (EC50 >100 µg/ml). These results revealed that resistance in Colletotrichum spp. to primary fungicides is widespread in the mid-Atlantic strawberry fields.


To burst or hide.
The transcription activator of the λ phage, CII, determines whether the phage will undergo the lytic or the lysogenic pathway. In a report by Zhao et al. in this issue of Structure, the cryo-EM structure of the λCII-dependent transcription activation complex reveals how λCII activates the PRE promoter to turn on the lysogenic pathway.


Influences of humic acid on the release of polybrominated diphenyl ethers from plastic waste in landfills under different environmental conditions.
Landfill-formed humic acid are an important substance in landfill leachate. The effect of landfill-formed humic acid in different environments (temperature and surfactant concentrations) on the release of chemicals from plastic waste remains unknown. In order to explore the pollution release rates of polybrominated diphenyl ethers (PBDEs) in different plastic waste, humic acid were used as the extractant to conduct leaching simulation tests to study the effects of time, temperature, and surfactant (sodium dodecyl benzene sulfonate (SDBS)) concentrations on the release of PBDEs in waste. This waste includes polypropylene random pipes (PPRP), polyethylene of raised temperature resistance pipes (PERTP), polyvinyl chloride pipes (PVCP), polypropylene plastic benches (PPB), polypropylene washing machines (PPWM), polystyrene television (PSTV), and flame-retardant acrylonitrile butadiene styrene (FRABS). The leaching amounts of PBDEs had significant linear growth over time. Among them, the leaching amount of PBDEs in daily plastics is lower than dismantling plastics. The rate of leaching of BDE-209 was greater than the other congeners, with a leaching amount of up to 93.10%. Different types of waste exhibited different changes with temperature and surfactants concentrations. Among all the waste types, the leaching amounts of PBDEs in PPRP and PERTP gradually increased with increasing temperature. Surfactants within a certain concentration range can promote the release of PBDEs. The purpose of the research is to explore the dissolution law of PBDEs of different plastic products and the same product in different environment, provides a theoretical basis for the management and risk control of landfills.


[Case report of a complete denture wearer in whom masticatory function improved by correcting horizontal maxillomandibular relationship].
A 68-year-old edentulous female patient with a chief complaint of mandibular residual mucous membrane pain during mastication was presented. Further investigation indicated ill-fitting mandibular dentures and masticatory dysfunction due to a dysfunctional horizontal maxillomandibular relationship. New complete dentures were fabricated that corrected the horizontal maxillomandibular relationship by Gothic arch tracing and selected an occlusal scheme for lingualized occlusion. Gothic arch tracing could establish adequate horizontal maxillomandibular relationship for this patient because the denture occlusal position shifted on the left side. Moreover, lateral forces in the dentures were decreased by lingualized occlusion. As a result, deviation of the complete denture set was decreased and the prognosis was favorable. The mandibular residual mucous membrane pain that was the chief complaint disappeared, masticatory function recovered, and the patient was satisfied with her new complete dentures.


Emerging role of exosomes in the pathology of chronic obstructive pulmonary diseases; destructive and therapeutic properties.
Chronic obstructive pulmonary disease (COPD) is known as the third leading cause of human death globally. Enhanced chronic inflammation and pathological remodeling are the main consequences of COPD, leading to decreased life span. Histological and molecular investigations revealed that prominent immune cell infiltration and release of several cytokines contribute to progressive chronic remodeling. Recent investigations have revealed that exosomes belonging to extracellular vesicles are involved in the pathogenesis of COPD. It has been elucidated that exosomes secreted from immune cells are eligible to carry numerous pro-inflammatory factors exacerbating the pathological conditions. Here, in this review article, we have summarized various and reliable information about the negative role of immune cell-derived exosomes in the remodeling of pulmonary tissue and airways destruction in COPD patients.


The Relationship between Korean Parents' Smartphone Addiction and That of Their Children: The Mediating Effects of Children's Depression and Social Withdrawal.
With the number of smartphone users growing around the world, children are using smartphones from an increasingly early age. Consequently, a significant number of children are being exposed to the risk of smartphone addiction, which is emerging as a serious social problem. Smartphone addiction can negatively impact children's physical, cognitive, and social development. Previous studies have demonstrated that parental smartphone addiction influences that of their children. Therefore, this study explores the relationship between parental smartphone addiction and children's smartphone addiction and the mediating effects of children's depression and social withdrawal. Data are drawn from National Youth Policy Institute's 2018 Korean Children and Youth Panel Survey. Respondents comprise 2011 fourth-grade elementary school students and their parents. Data were analyzed using SPSS version 21.0 and AMOS 21.0 software. Results show that the relationship between parental smartphone addiction and that of their children has a significantly positive mediating effect on children's social withdrawal, but no such effect on children's depression and there were no serial effects of children's depression and social withdrawal. Consequently, educational programs that control parents' smartphone usage, improve the parent-child relationship, and engender social sensitivity should be developed to reduce and prevent smartphone addiction among children.


Fuzzy detection of EEG alpha without amplitude thresholding.
Intelligent automated systems are needed to assist the tedious visual analysis of polygraphic recordings. Most systems need detection of different electroencephalogram (EEG) waveforms. The problem in automated detection of alpha activity is the large inter-individual variability of its amplitude and duration. In this work, a fuzzy reasoning based method for the detection of alpha activity was designed and tested using a total of 32 recordings from seven different subjects. Intelligence of the method was distributed to features extracted and the way they were combined. The ranges of the fuzzy rules were determined based on feature statistics. The advantage of the detector is that no alpha amplitude threshold needs to be selected. The performance of the alpha detector was assessed with receiver operating characteristic (ROC) curves. When the true positive rate was 94.2%, the false positive rate was 9.2%, which indicates good performance in sleep EEG analysis.


Verbascoside derivatives and iridoid glycosides from Penstemon crandallii.
The new phenylethanoid glycosides 2-O-acetyl-3'''-O-methylverbascoside and 2,4"-di-O-acetyl-3'''-O-methylverbascoside were isolated and identified from Penstemon crandallii. The major iridoid glycoside was plantarenaloside and no aucubin type iridoids were found. This contrasted with a previous analysis of P. teucrioides, from the same Penstemon subsection, which was dominated by aucubin derivatives.


Clinical and immunohistological characterization of cutaneous lesions in chronic lymphocytic leukaemia.
Twenty-five patients with immunologically classified B cell chronic lymphocytic leukaemia (CLL) were examined for skin lesions. Six showed evidence of cutaneous involvement, and histological examination of skin biopsies from these patients revealed perivascular lymphocytic infiltration with some diffuse involvement in three. Immunohistological analysis with a range of B and T cell specific monoclonal antibodies revealed that in all cases the infiltrate was predominantly T cell in origin and that epidermotropism in three cases was also associated with T cell components. Six control patients with macroscopically normal skin were also biopsied and these biopsies subjected to the same assessment. All were normal.


Ligand-receptor interactions in affinity cell partitioning. Studies with transferrin covalently linked to monomethoxypoly(ethylene glycol) and rat reticulocytes.
The partitioning of rat reticulocytes in poly(ethylene glycol) (PEG)-dextran two-phase systems increases into the PEG-rich top phase when the cells are incubated with transferrin covalently modified with monomethoxy-PEG (MPEG-transferrin) prior to partitioning. Two observations support the suggestion that such an increase in top-phase partitioning is due to the specific interaction of the MPEG-transferrin conjugate with the transferrin receptor on the surface of the reticulocyte: first, the MPEG-transferrin conjugate competes with [125I]transferrin for the transferrin receptor on reticulocytes (Ka = 6.28 x 10(6) l mol-1); and second, the MPEG-modified transferrin is unable to change the partitioning of rat erythrocytes, cells lacking the transferrin receptor. This example illustrates the feasibility of manipulating the partitioning of a selected cell population when ligand-receptor interactions are exploited. The increase in the partitioning of the reticulocytes takes place within a narrow range of MPEG-transferrin bound per cell, viz., 10.2-11.3 fg per cell. The latter range corresponds to ca. 80,000-89,000 molecules of MPEG-transferrin bound per cell.


The antihyperlipidemic activities of 4(3H) quinazolinone and two halogenated derivatives in rats.
In the present study, the effects of subchronic treatments (4 weeks) of hypercholesterolemic (single) and diabetic-hypercholesterolemic (combined) rats with 4 (3H) quinazolinone and 2 halogenated derivatives (6, 8-dibromo-2-methy-4 (3H) quinazolinone and 6-iodo-2-methyl-4(3H) quinazolinone) at a sublethal dose level (2 mg/Kg) on cholesterol metabolism were investigated. Bezafibrate, a hypolipidemic drug was used as a reference compound for data comparison. Treatment of rats with single and combined hypercholesterolemia with quinazolinone compounds gave rise to highly significant reductions in serum total cholesterol and cholesterol ester levels, whereas serum triacylglycerol level was significantly reduced only after treatment with halogen-substituted quinazolinones in single hyper-cholesterolemia, compared to the control group. The effects of different quinazolinones and bezafibrate on reduction of serum LDL-C level were comparable in single hypercholesterolemia but significantly different in combined hypercholesterolemia. Results obtained from this study suggest that the antihyperlipidemic effect of quinazolinone compounds was brought about by inhibition of dietary cholesterol absorption and / or intestinal ACAT activity.


Beneficial effects of SS-31 peptide on cardiac mitochondrial dysfunction in tafazzin knockdown mice.
Barth Syndrome (BTHS), a genetic disease associated with early-onset cardioskeletal myopathy, is caused by loss-of-function mutations of the TAFAZZIN gene, which is responsible for remodeling the mitochondrial phospholipid cardiolipin (CL). Deregulation of CL biosynthesis and maturation in BTHS mitochondria result in a dramatically increased monolysocardiolipin (MLCL)/CL ratio associated with bioenergetic dysfunction. One of the most promising therapeutic approaches for BTHS includes the mitochondria-targeted tetrapeptide SS-31, which interacts with CL. Here, we used TAFAZZIN knockdown (TazKD) mice to investigate for the first time whether in vivo administration of SS-31 could affect phospholipid profiles and mitochondrial dysfunction. The CL fingerprinting of TazKD cardiac mitochondria obtained by MALDI-TOF/MS revealed the typical lipid changes associated with BTHS. TazKD mitochondria showed lower respiratory rates in state 3 and 4 together with a decreased in maximal respiratory rates. Treatment of TazKD mice with SS-31 improved mitochondrial respiratory capacity and promoted supercomplex organization, without affecting the MLCL/CL ratio. We hypothesize that SS-31 exerts its effect by influencing the function of the respiratory chain rather than affecting CL directly. In conclusion, our results indicate that SS-31 have beneficial effects on improving cardiac mitochondrial dysfunction in a BTHS animal model, suggesting the peptide as future pharmacologic agent for therapy.


[Complex implantation of an automatic defibrillator-cardioverter through a left superior vena cava].
We describe the case of a 19-year-old girl with a left superior vena cava and a surgically corrected complete atrioventricular canal defect. After an inhospital sudden death an automatic defibrillator-cardioverter was implanted through her left superior vena cava. During the postoperative course, multiple inappropriate discharges caused by myopotential oversensing indicated the relocation of the electrode and, finally, insertion of two epicardial leads by a left submammarian thoracotomy approach, produced an optimal result.


Near infra-red photoluminescent graphene nanoparticles greatly expand their use in noninvasive biomedical imaging.
A simple reaction process is developed to synthesize blue, green, yellow and red colour graphene nanoparticles (GNPs) from carbon fibers. Here, we have focused on synthesis of near infra-red GNPs and their biological application for optical imaging of deep tissues and organs.


Evolutionary considerations in the development of chronic pelvic pain.
Chronic pelvic pain is common among women of reproductive age and is associated with significant morbidity and comorbidities. In this Viewpoint, we explore the evolutionary cause of pelvic pain and summarize evidence that supports a menstruation-related evolutionary cause of chronic visceral pelvic pain: (1) lifetime menstruation has increased; (2) severe dysmenorrhea is common in the chronic pelvic pain population, particularly among those with pain sensitization; and (3) a potential biological mechanism can be identified. Thus, chronic pelvic pain may arise from the mismatch between the slow pace of biological evolution in our bodies and the relatively rapid pace of cultural changes that have resulted in increased menstrual frequency due to earlier menarche, later mortality, and lower fecundity. One possible mechanism that explains the development of persistent pain from repeated episodes of intermittent pain is hyperalgesic priming, a physiological process defined as a long-lasting latent hyperresponsiveness of nociceptors to inflammatory mediators after an inflammatory or neuropathic insult. The repetitive severely painful menstrual episodes may play such a role. From an evolutionary perspective the relatively rapid increase in lifetime menstruation experience in contemporary society may contribute to a mismatch between lifetime menstruation and the physiological pain processes, leading to a maladaptive state of chronic visceral pelvic pain. Our current physiology does not conform to current human needs.


Educating for the Future: a Preliminary Investigation of Doctoral-Level Clinical Psychology Training Program's Implementation of Telehealth Education.
Literature has reinforced the importance of telehealth-focused education to foster provider competence and optimal patient care. As clinical psychology evolves to meet field needs, many have suggested graduate school as an optimal time to offer comprehensive telehealth education. Despite the rapid expansion of telehealth post-COVID-19, the extent of telehealth-specific doctoral-level programming, as well as the foci of available trainings, has remained unclear. To address this gap and inform future work, the current study evaluated doctoral-level clinical psychology training programs throughout the USA. Fourteen doctoral-level training programs completed author-created REDCap-hosted demographic and telehealth training surveys. Pre-COVID-19, three of fourteen programs reported implementing some form of telehealth-focused education, with a majority of the information being viewed as optional targets for instructors. Contrastingly, thirteen programs indicated implementing telehealth-focused education post-COVID-19, with a majority of the information being indicated as mandatory educational targets. Despite increases in educational activities, a large number of programs endorsed a desire for additional telehealth-focused education for students as they transition into future roles. Educational foci, methods of training, and instructor preparation are discussed. While participation was limited, the current study demonstrated positive trends in the development of telehealth-focused education. Nevertheless, there remains an ongoing need for both specialized coursework and a wider range of educational topics. Ultimately, the current study is believed to have provided a preliminary evaluation of the types and foci of telehealth-focused education among doctoral-level clinical psychology training programs.


Periaortic hematoma at diaphragmatic crura at helical CT: sign of blunt aortic injury in patients with mediastinal hematoma.
To evaluate periaortic hematoma (PH) near the level of the diaphragm at abdominal computed tomography (CT) as an indirect sign of acute traumatic aortic injury after blunt trauma in patients with mediastinal hematoma. From 1998 to 2001, 97 patients with CT evidence of mediastinal hematoma after blunt thoracic trauma were retrospectively identified at two level 1 trauma centers. The presence or absence of PH near the level of the diaphragmatic crura was retrospectively established by a blinded reviewer at each institution. Aortic injury status was determined by reviewing angiographic, surgical, and clinical records. Sensitivity, specificity, positive and negative productive values, and positive and negative likelihood ratios were calculated. Among the 97 patients with mediastinal hematoma, 14 had both PH near the level of the diaphragm and aortic injury; six had aortic injuries without PH, five had PH near the level of the diaphragm without aortic injury, and 72 had no evidence of PH near the diaphragm and no aortic injury. Sensitivity for PH near the level of the diaphragm as a sign of aortic injury was 70%; specificity, 94%; positive predictive value, 74%; and negative predictive value, 92%. The positive likelihood ratio for the presence of aortic injury was 10.8, and the negative likelihood ratio was 0.3. PH near the level of the diaphragmatic crura is an insensitive but relatively specific sign for aortic injury after blunt trauma. The presence of this sign at abdominal CT should prompt imaging of the thoracic aorta to evaluate potential thoracic aortic injury.


Identification of gastric cancer risk markers that are informative in individuals with past H. pylori infection.
Epigenomic damage induced by Helicobacter pylori infection is accumulated in gastric mucosae before the development of malignancy. In individuals without current H. pylori infection, DNA methylation levels of specific CpG islands (CGIs) are associated with gastric cancer risk. Because risk estimation in individuals with past infection is clinically important, we here aimed to identify the risk markers that reflect epigenomic damage induced by H. pylori infection, and that are informative in these individuals. Gastric mucosae were obtained from 55 gastric cancer patients (GC-Pt) (21 with current infection and 34 with past infection) and 55 healthy volunteers (HV) (7 never-infected, 21 with current infection, and 27 with past infection). Hypermethylated CGIs were searched for by methylated DNA immunoprecipitation-CGI microarray, and methylation levels were analyzed by quantitative methylation-specific polymerase chain reaction (PCR). By microarray analysis of a pool of three samples from GC-Pt with past infection and another pool of samples from HV with past infection, 15 hypermethylated CGIs in the former pool were isolated. Seven of them had significantly higher methylation levels in GC-Pt with past infection (n = 10) than in HV with past infection (n = 10) (P < 0.001). In a validation cohort (21 GC-Pt with past infection and 14 HV with past infection), the seven new markers had large areas under the receiver-operating characteristic curves (0.78-0.84) and high odds ratios (12.7-36.0) compared with two currently available markers (0.60-0.65, 5.0-5.7). We identified seven novel gastric cancer risk markers that are highly informative in individuals with past infection.


Eating disorders in patients with type 1 diabetes: a meta-analysis.
A meta-analysis of controlled studies on prevalence of eating disorders in Type 1 diabetes was performed in order to assess differences between diabetic and non-diabetic female subjects. All controlled studies using the Diagnostic and Statistical Manual of Mental Disorders Third Edition Revised (DSM Ill-R) or the DSM Fourth Edition (DSM IV) criteria for interview-based diagnosis were included in the analysis. The total sample was composed of 748 and 1587 female subjects with and without diabetes, respectively. The prevalence of anorexia nervosa (AN) in Type 1 diabetic subjects was not significantly different from that of controls (0.27 vs 0.06%), while that of bulimia nervosa and of the two conditions combined was significantly higher in diabetic patients (1.73 vs 0.69%, and 2.00 vs 0.75%, respectively; both p < 0.05). Type 1 diabetes is associated with a higher prevalence of bulimia nervosa in females.


The spatial scale of seed collection by harvester ants.
Colonies of the seed-eating ant, Pogonomyrmex barbatus, compete with neighboring colonies for foraging areas. In a conflict over foraging area, what is at stake? This depends on how resources are distributed in time and space: if certain regions consistently provide particularly nutritious seed species, or especially abundant seeds, such regions will be of greater value to a colony. During the summer, seeds were taken from returning foragers in colonies located in 4 different vegetation types. There was no relation between the vegetation currently growing in the foraging area, and the species of seeds collected by ants. During the summer, ants collect mostly seeds produced in previous seasons and dispersed by wind and flooding. In 1991, colonies in all vegetation types collected mostly Bouteloua aristidoides; in 1992, Eriastrum diffusum and Plantago patagonica. There was no relation between colony density and numbers of seeds collected. Seed species collected by ants were compared in different colonies, and on different foraging trails within a colony. The results show that seed patches are distributed on the scale of distances between nests, not the smaller scale of different foraging trails of one colony. It appears that colonies are competing for any space in which to search for seeds, not competing for certain regions of consistently high value.


Successful management of unilateral congenital patellar tendon aplasia: case report.
Anatomical variation is discovered frequently in humans, and much such variation in the musculoskeletal system has been reported. We present a rare case of unilateral congenital patellar tendon aplasia with concomitant apparent shortness of the bilateral halluces as a result of shortened first metatarsals as an anatomical variant.


Prediction improvement of potential PV production pattern, imagery satellite-based.
The results obtained by using an existing model to estimate global solar radiation (GHI) in three different locations in Tunisia. These data are compared with GHI meteorological measurements and PV_Gis satellite imagery estimation. Some statistical indicators (R, R2, MPE, AMPE, MBE, AMBE and RMSE) have been used to measure the performance of the used model. Correlation coefficient for the different stations was close to 1.0. The meteorology and satellite determination coefficient (R2) were also near 1.0 except in the case of Nabeul station in which the meteorology measurements (R) were equals to 0.5848 because of the loss of data in this location due to meteorological conditions. This numerical model provides the best performance according to statistical results in different locations; therefore, this model can be used to estimate global solar radiation in Tunisia. The R square values are used as a statistical indicator to demonstrate that the model's results are compatible with those of meteorology with a percentage of error less than 10%.


Combinational administration of mesenchymal stem cell-derived exosomes and metformin reduces inflammatory responses in an in vitro model of insulin resistance in HepG2 cells.
Diabetes is a highly common metabolic disorder in advanced societies. One of the causes of diabetes is insulin resistance, which is associated with a loss of sensitivity to insulin-sensitive cells. Insulin resistance develops in the body of a person prone to diabetes many years before diabetes development. Insulin resistance is associated with complications such as hyperglycemia, hyperlipidemia, and compensatory hyperinsulinemia and causes liver inflammation, which, if left untreated, can lead to cirrhosis, fibrosis, and even liver cancer. Metformin is the first line of treatment for patients with diabetes, which lowers blood sugar and increases insulin sensitivity by inhibiting gluconeogenesis in liver cells. The use of metformin has side effects, including a metallic taste in the mouth, vomiting, nausea, diarrhea, and upset stomach. For this reason, other treatments, along with metformin, are being developed. Considering the anti-inflammatory role of mesenchymal stem cells (MSCs) derived exosomes, their use seems to help improve liver tissue function and prevent damage caused by inflammation. This study investigated the anti-inflammatory effect of Wharton's jelly MSCs derived exosomes in combination with metformin in the HepG2 cells insulin resistance model induced by high glucose. This study showed that MSCs derived exosomes as an anti-inflammatory agent in combination with metformin could increase the therapeutic efficacy of metformin without needing to change metformin doses by decreasing inflammatory cytokines production, including IL-1, IL-6, and TNF-α and apoptosis in HepG2 cells.


Serum cytokines and chronic fatigue in adults surviving after childhood leukemia and lymphoma.
Fatigue is a common and distressing symptom in all phases of the cancer trajectory. Chronic fatigue (CF) is defined as fatigue with duration ⩾6months. The etiology of CF in cancer survivors is poorly understood, but a link to inflammatory activity has been suggested. In the present study we explored the relation between CF and the levels of 17 cytokines among a national representative sample of 232 adult survivors after childhood lymphoma and acute lymphoblastic leukemia (ALL). Chalder's fatigue questionnaire assessed CF. The sera of the survivors were analyzed for 27 cytokines, where of 17 were detectable. Median age at survey and diagnosis was 29.7years (range 18.6-54.5years) and 9.6years (range 0.3-18.0years), respectively. Median follow-up time was 21.5years (range 7.1-40.0years). CF was not associated with increased levels of any of the 17 detectable cytokines when all three diagnostic groups were included in the analyses. In sub-analyses of the non-Hodgkin lymphoma survivors only, those with CF had significant higher levels of IL-9, FGF, PDGF and eotaxin compared to those without CF (p<0.05). Gender, age, diagnosis, obesity, or reduced heart function did not impact upon the results. Differences in cytokine levels between the diagnostic groups were observed irrespective of the presence/absence of CF. This study could not confirm a relation between levels of cytokines and CF in adults who survived childhood lymphoma and ALL, except for among NHL survivors. Despite the broad spectrum of cytokines and relatively large sample, small aberrances may not have been traced.


Functional characterization of active transport of progesterone to adrenal cells.
The characterization of the transport mechanism of progesterone, which is one of the neutral steroids in the adrenal cells, has been studied by the examination of progesterone uptake into the monolayers of SW-13 cells (a human adrenal adenocarcinoma cell line). The uptake of [(3)H]progesterone at a tracer concentration (1 nM) exhibited temperature, pH and sodium dependency. According to kinetic analysis of the concentration dependence, the uptake of progesterone involves saturable and non-saturable processes. The uptake for the saturable process, which gave K(t) values (half-saturation concentration) of 4.7 +/- 8.7 microM, was inhibited by metabolic inhibitors and amino-acid modifiers but not by endocytosis inhibitors or substrates for known transporters. The uptake of progesterone was also inhibited by several neutral steroids but not by anionic steroids. The inhibition by both beta-estradiol and estriol was competitive. The uptake of progesterone by the adrenal cells might be at least partially accounted for by a specific carrier-mediated transport mechanism generated by sodium ions and an electrochemical mechanism.


In vitro evaluation of the effect of post system and length on the fracture resistance of endodontically treated human anterior teeth.
The aim of this study was to evaluate the effect of post system and length on the fracture resistance of endodontically treated human anterior teeth. Seventy-five extracted human incisors were endodontically treated, out of which 60 were decoronated 2 mm above the cementoenamel junction and divided into two experimental groups based on the type of post system to be used: glass fiber post (GFP) and Ribbond fiber post groups (RFP). Endodontically treated human anterior teeth in which no post was placed served as control group. Each group was divided into two subgroups according to the length of post space: 5 and 10 mm and all the samples were restored with metal crowns. The fracture resistance was measured by applying loads at an angle of 130° to the long axis of teeth in an Instron universal testing machine. The results revealed that GFP group at 10-mm post space length showed the significantly highest fracture resistance (740.2133 N) among all groups and subgroups. Decrease in post length resulted in the decrease in fracture resistance in GFP group (425.1867 N), whereas in group RFP 5-mm subgroup (299.6200 N) showed significantly higher fracture resistance than 10-mm subgroup (216.9300 N) but lesser than the control (437.8733 N) in both the subgroups. Glass fiber posts efficiently increase the fracture resistance of an endodontically treated tooth but the determination of optimal post length is also essential. The present investigation highlights the significance of using glass fiber posts in the restoration of endodontically treated teeth. Endodontically treated teeth restored with glass fiber posts showed increased fracture strength and favorable mode of fracture, and are therefore highly recommended to achieve better clinical outcomes.


[Effect of thyroid inhibitors and thyroidectomy on sialic acid content of rat blood and liver].
Effect of experimental hypothyreosis, caused by various thyrostatic agents, on content of sialic acids was studied in blood plasma and liver tissue of white rat males. In hypothyreosis content of sialic acids was distinctly increased in blood serum but decreased in homogenate and structure elements of liver tissue. Alteration in content of sialic in blood plasma correlated with their content in liver structure elements. Content of sialic acids in blood plasma and liver tissue was shown to depend on dosage and length of administration of various thyrostatic preparations. Mechanism of increase in concentration of sialic acids in blood serum under influence of experimental hypothyreosis is discussed.


Plasma prostanoids in pregnancy-induced hypertension.
The concentrations of 13,14-dihydro-15-oxo-prostaglandin F2 alpha (PGFM), 6-oxo-prostaglandin F1 alpha (6-oxo-PGF1 alpha) and thromboxane B2 (T X B2) were measured by radioimmunoassay in peripheral plasma from 183 pregnancy women attending routine antenatal clinics. A total of 141 patients (47 nulliparous, 94 parous) remained normotensive and had uncomplicated pregnancies. The results from this group showed that there was no significant difference in the concentration of any metabolite in relation to parity or gestational age. The concentrations (pmol/l; means +/- SD) were PGFM 373 +/- 105, 6-oxo-PGF1 alpha 391 +/- 104 and T X B2 373 +/- 121. Nineteen patients (12 nulliparous, 7 parous) who had pregnancy-induced hypertension (PIH) by the time of sampling (three) or who subsequently developed the symptom (mean time from sampling to diagnosis 11 weeks, range 1-24 weeks) had significantly higher levels of 6-oxo-PGF1 alpha (574 +/- 216; P less than 0.0005, Student's t-test) and T X B2 (603 +/- 268; P less than 0.0005). The concentrations in seven nulliparous patients with PIH and proteinuria were 656 +/- 276 for 6-oxo-PGF1 alpha and 754 +/- 228 pmol/l for T X B2.


The nuclear receptor and clock gene REV-ERBα regulates cigarette smoke-induced lung inflammation.
REV-ERBα is a nuclear heme receptor, transcriptional repressor and critical component of the molecular clock that drives daily rhythms of metabolism. Evidence reveals that REV-ERBα also plays an important regulatory role in clock-dependent lung physiology and inflammatory responses. We hypothesize that cigarette smoke (CS) exposure influences REV-ERBα abundance in the lungs, facilitating a pro-inflammatory phenotype. To determine the impact of REV-ERBα activation in the CS-induced inflammatory response we treated primary human small airway epithelial cells (SAECs) with CS extract (CSE) or lipopolysaccharide (LPS) in the absence or presence of pre-treatment with the REV-ERBα agonist GSK 4112. We also exposed adult C57BL/6J (WT) and Rev-erbα global KO mice to CS (10 and 30 days) and measured pro-inflammatory cytokine release. Our data reveal that pre-treatment with GSK 4112 reduced CSE/LPS induced pro-inflammatory cytokines release from both SAECs and mouse lung fibroblasts (MLFs). Furthermore, REV-ERBα KO mice show a greater inflammatory response to 10 and 30 days of CS, including increased neutrophil lung influx, pro-inflammatory cytokine (IL-6, MCP-1 and KC) release, and pro-senescence marker (p16) when compared to WT mice. These data demonstrate that REV-ERBα is a critical regulator of CS-induced lung inflammatory responses.


Gut microbiota: An intermediary between metabolic syndrome and cognitive deficits in schizophrenia.
Gut microbiome interacts with the central nervous system tract through the gut-brain axis. Such communication involves neuronal, endocrine, and immunological mechanisms, which allows for the microbiota to affect and respond to various behaviors and psychiatric conditions. In addition, the use of atypical antipsychotic drugs (AAPDs) may interact with and even change the abundance of microbiome to potentially cause adverse effects or aggravate the disorders inherent in the disease. The regulate effects of gut microbiome has been described in several psychiatric disorders including anxiety and depression, but only a few reports have discussed the role of microbiota in AAPDs-induced Metabolic syndrome (MetS) and cognitive disorders. The following review systematically summarizes current knowledge about the gut microbiota in behavior and psychiatric illness, with the emphasis of an important role of the microbiome in the metabolism of schizophrenia and the potential for AAPDs to change the gut microbiota to promote adverse events. Prebiotics and probiotics are microbiota-management tools with documented efficacy for metabolic disturbances and cognitive deficits. Novel therapies for targeting microbiota for alleviating AAPDs-induced adverse effects are also under fast development.


The Use of Donation After Circulatory Death Organs for Simultaneous Liver-kidney Transplant: To DCD or Not to DCD?
Because of the challenges with organ scarcity, many centers performing simultaneous liver-kidney transplant (SLKT) are opting to accept donation after circulatory death (DCD) organs as a means of facilitating earlier transplant and reducing death rates on the waitlist. It has been suggested, however, that DCD organs may have inferior graft and patient survival posttransplant compared with donation after neurologic death (DND) organs. We created a Markov model to compare the overall outcomes of accepting a DCD SLKT now versus waiting for a DND SLKT in patients waitlisted for SLKT, stratified by base Model for End-Stage Liver Disease (MELD) score (≤20, 21-30, >30). Waiting for DND SLKT was the preferred treatment strategy for patients with a MELD score of 30 or less (incremental value of 0.54 and 0.36 quality-adjusted life years for MELD score of 20 or less and MELD score of 21 to 30 with DND versus DCD SLKT, respectively). The option to accept a DCD SLKT became the preferred choice for those with a MELD score greater than 30 (incremental value of 0.31 quality-adjusted life years for DCD versus DND SLKT). This finding was confirmed in a probabilistic sensitivity analysis and persisted when analyzing total life years obtained for accept DCD versus do not accept DCD. There is a benefit to accepting DCD SLKT for patients with MELD score greater than 30. Although not accepting DCD SLKT and waiting for DND SLKT is the preferred option for patients with MELD of 30 or less, the incremental value is small.


Inter-tester reliability of passive intervertebral and active movements of the cervical spine.
Measurements of active range of motion (AROM) and passive intervertebral movements (PIM) of the cervical spine are frequently used for patients with neck pain. However, there is a paucity of studies that investigate the psychometric properties of these measurements. Objectives of this study were to: (1) determine the inter-tester reliability of PIM, AROM, and the effects of AROM on symptom provocation; (2) establish the minimal detectable change (MDC) in cervical AROM; and (3) determine the association between AROM and disability. Thirty subjects (age 41+/- 12) with neck pain participated in this study. Two masked examiners performed the measurements during the same testing session. PIM was assessed manually and recorded as hypomobile or normal. AROM was measured in degrees with a gravity goniometer. The effect of AROM on patient's symptoms was recorded as no change, decreased, increased, centralization, or peripheralization. Measures of AROM had moderate to substantial reliability (.78 - .91) and resulted in a MDC adequate for clinical use (from 9 degrees to 16 degrees). The effect of AROM on symptom provocation resulted in Kappa values that ranged from slight to substantial (.25 - .87). Measures of PIM resulted in substantial and moderate reliability of assessing occipital-atlas mobility, tenderness of the transverse processes of atlas, and symptom provocation during PIM testing of the lower cervical segments. Fair Kappa values were observed during judgment of mobility in the C2 segment and symptom reproduction during PIM of C2 and C5. The additional PIM had Kappa values that ranged from none to slight. Low prevalence of positive findings likely resulted in an artificial deflation of the Kappa statistic during some PIM measures. Measures of AROM in saggital and transverse planes were associated with disability scores (r = .43 and .40, respectively). Findings are relevant to the planning of future studies to establish the criterion validity of these tests to guide the selection of interventions and establish prognosis in patients with neck pain.


Stanford type A aortic dissection with pulmonary arterial intramural hematoma and pulmonary hemorrhage.
A rare complication of a Stanford type A aortic dissection is extension along the pulmonary arteries. We present a case that shows main and right pulmonary artery intramural hematoma and pulmonary hemorrhage in an 80-year-old woman who presented with a type A Stanford aortic dissection. The 11-month follow-up multidetector CT angiogram for this patient showed that the right pulmonary artery had become aneurysmal.


Violation of research integrity principles occurs more often than we think.
The science community generally believes that the violation of research integrity is rare. Built upon this belief, the scientific system makes little effort to examine the trustworthiness of research. Research misconduct refers to an intentional violation of research integrity principles, which has an extensive and far-reaching impact on the trustworthiness and reputation of science. Emerging evidence has suggested that research misconduct is far more common than we normally perceive. Far more problematic papers should be retracted than are being retracted because of poor actions when confronting research misconduct. Research misconduct is usually driven by incentives in the form of pursuing publications for researchers' career needs and is further facilitated by poor research governance. The current strategy that tackles potential research misconduct focuses on protecting the reputation of authors and their institutions but neglects the interests of patients, clinicians and honest researchers. Removing improper incentives, training researchers and imposing better governance are vital to reducing research misconduct. Awareness of the possibility of misconduct and formalized procedures that scrutinize study trustworthiness are important during peer review and in systematic reviews.


Clinical Features and Prognoses of Patients With Breast Cancer Who Underwent Surgery.
Breast cancer (BC) remains a pervasive malignant neoplasm worldwide, with increasing incidence. However, there are a scarcity of studies examining the clinical characteristics and prognosis of Chinese patients with BC who have undergone surgery. To evaluate overall survival (OS) and disease-free survival (DFS) in patients with surgically treated BC in China, focusing on histopathology and surgical approach. This cohort study included a retrospective review of the medical records of patients with unilateral BC who underwent surgery between January 2009 and September 2017, with a median follow-up time of 7.69 years. Clinical features were extracted from these records, and survival analysis was performed. Data analysis was conducted in March 2023. Patients' OS and DFS. The study included 14 782 patients (14 724 [99.6%] female patients; mean [SD] age, 51.6 [10.9] years). Invasive ductal carcinoma (IDC) was the most prevalent type, observed in 12 671 patients (85.6%). Stages 0, I, II, III, and IV accounted for 6.4% (919 patients), 32.0% (4579 patients), 40.5% (5791 patients), 20.2% (2896 patients), and 0.9% (126 patients) of cases, respectively. Hormone receptor (HR) positivity was observed in 10 241 patients (75.1%), and 3665 (29.1%) tested positive for ERBB2 (formerly HER2/neu). The HR-negative-ERBB2-negative, HR-negative-ERBB2-positive, HR-positive-ERBB2-negative, and HR-positive-ERBB2-positive subtypes constituted 13.3% (1666 patients), 12.7% (1595 patients), 57.8% (7251 patients), and 16.2% (2034 patients) of cases, respectively. Breast-conserving surgery (BCS) was performed in 2884 patients (19.5%). The 5-year and 10-year OS rates were 92.9% (13 689 of 14 732) and 87.4% (3287 of 3760), while the 5-year and 10-year DFS rates were 89.0% (12 916 of 14 512) and 82.9% (3078 of 3713), respectively. Multivariate analysis found that for patients with IDC, age, BCS, invasive tumor size, tumor grade, lymphovascular invasion (LVI), the number of lymph node metastases (LNMs), distant metastasis, Ki67, and HR status were associated with OS, whereas invasive tumor size, tumor grade, LVI, the number of LNMs, HR status, and ERBB2 status were associated with DFS. After propensity score matching, BCS was equivalent to mastectomy with respect to survival in patients with IDC. This cohort study of patients with BC who underwent surgery in China provides valuable insights into the histopathological characteristics and survival outcomes of this population. The diverse histopathological features emphasize the necessity for customized treatment strategies. The relatively low BCS rate in the study population suggests the need for heightened awareness and adoption of this approach, considering its potential advantages for survival.


Modified immunotherapy for alopecia areata.
Squaric acid dibutylester (SADBE) is a commonly used contact sensitizer in immunotherapy for alopecia areata (AA). Severe contact dermatitis is induced by the currently high recommended sensitization dose of 1%-2% SADBE, often decreasing patient compliance. We assessed a modified immunotherapy for AA using SADBE at a starting concentration of 0.01% without sensitization. After one or two weeks of initial 0.01% SADBE application, the concentration of SADBE was increased gradually to 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 1% and 2% until the patients felt itching or erythema at the AA lesion site. The modified immunotherapy showed a response rate of 69.4% (25/36), equivalent to conventional immunotherapy using SADBE starting at 1%-2% sensitization. Furthermore, we investigated the combination therapy of SADBE and multiple courses of steroid pulses for AA. The response rate for combination therapy was 73.7% (28/38); however, the group receiving combination therapy showed a significant prevalence of severe AA compared with the group receiving modified immunotherapy only. We reviewed the efficacy and safety of modified immunotherapy without initial sensitization and combination therapy with immunotherapy and multiple courses of pulses for AA.


Emotional intelligence as a mediator between attachment security and empathy in pre-clinical medical students: A multi-center cross-sectional study.
To explore the association of emotional intelligence (EI) and attachment security (AS) with empathy dimensions in medical students by examining the mediating role of EI. In a cross-sectional design, the Interpersonal Reactivity Index (IRI), the Emotional Quotient Inventory (EQ-i), the Attachment Style Questionnaire (ASQ), and demographic questions were administrated to second-year medical students of two medical schools in Northern Italy. 253 medical students (56.13% female), aged 19-29, participated in this study. AS positively correlated to Empathic Concern (r = 0.17, p = 0.008) and Perspective Taking (r = 0.24, p < 0.001), and negatively to Personal Distress (r = -0.33, p < 0.001). Individuals with the same level of AS and a higher score on EQ-i had a higher score (β = 0.072, p = 0.033) on empathy latent factor (at the basis of Empathic Concern and Perspective Taking) and a lower score (β = -0.290, p < 0.001) on Personal Distress than those with a lower EQ-i score. This study shows that EI completely mediated the relationship between AS and empathy dimensions among medical students. EI training and workshop should be considered when designing educational interventions and programs to enhance empathy and decrease interpersonal distress in medical students.


Cadmium induced cardiac oxidative stress in rats and its attenuation by GSP through the activation of Nrf2 signaling pathway.
Cadmium (Cd) is one of the toxic heavy metals in the environment, which induces oxidative stress, dyslipidemia and membrane disturbances in heart. The present study was designed to evaluate the role of grape seed proanthocyanidins (GSP) against Cd induced oxidative stress mediated cardio-toxicity in rats. In this study, male Wistar rats were treated with Cd as cadmium chloride (CdCl2, 5 mg/ kg bw, PO) and pre-administered with GSP (100 mg/kg bw, PO) 90 min before the Cd intoxication for 4 weeks. Our results demonstrate a significant increase in the levels of cardiac troponins T and I (cTnT & I), cardiac serum markers, lipid peroxidative markers and plasma total cholesterol (TC), triglycerides (TG), phospholipids (PL) and free fatty acids (FFA). Cd induced oxidative stress decreased the levels of mitochondrial Krebs cycle enzymes as well as the respiratory chain enzyme activities and altered the levels of cardiac enzymatic and non-enzymatic antioxidants. The inflammatory (NF-kB, NO, TNF-α, IL-6), apoptotic markers (caspase 3, cytochrome C, Bax, Bcl-2), membrane bound ATPases and antioxidant Nrf2 (HO-1, keap1) markers were also measured in the control and experimental rats. All these alterations caused by Cd could be lessened by the pre-supplementation of GSP. The pre-administration of GSP significantly increased the activities of mitochondrial and respiratory chain enzymes, reduced the levels of cardio-oxidative stress markers in Cd-treated rats, which examines the stress stabilizing action of GSP. GSP also prevented the cytochrome C release, inhibited the caspase activation and maintained the ratio of Bcl-2/Bax by its free radical scavenging ability. Nrf2 expression was transiently increased while the impaired cardiac markers were restored near to their basal levels by the pre-treatment with GSP in Cd intoxicated rats. The cardioprotective nature of the GSP was further fortified by our light microscopic and ultra structural findings. Overall, our results suggest that GSP has an ability to inhibit the membrane disturbances in cardiomyocytes, apoptotic pathway, inflammation and activate the Nrf2 expression through which it recuperated the Cd induced oxidative stress mediated cardiac dysfunction.


Long-term Toxicity of Cancer Treatment in Older Patients.
With earlier cancer diagnosis among older patients with cancer, the possibility of curing cancer increases. However, cancer treatment may have a long-lasting impact on older cancer survivors. It is vital to screen, diagnose, and properly manage the long-term toxicities of cancer treatment in order to maintain the quality of life of older cancer survivors.


Do clinical evaluations in a psychiatry clerkship favor students with positive personality characteristics?
The authors examine associations of personality characteristics, National Board of Medical Examiners subject examination performance, and Objective Structured Clinical Examination performance with clinical evaluations of third-year medical students in a psychiatry clerkship. Students completed the Revised NEO Personality Inventory, which measures personality domains of neuroticism, extraversion, openness, agreeableness, and conscientiousness and associated personality traits. At clerkship completion, students completed the National Board of Medical Examiners subject examination and a psychiatry Objective Structured Clinical Examination, and were evaluated by attending physicians (using a standardized evaluation form) regarding their clinical "knowledge and skill" and "interpersonal behavior." Data were analyzed using Pearson correlation and canonical correlation. National Board of Medical Examiners subject examination and Objective Structured Clinical Examination scores were uncorrelated with clinical evaluations of "knowledge and skill" and "interpersonal behavior." Personality variables explained a moderate amount of variance in clinical evaluations. "Knowledge and skill" was positively associated with the domain of conscientiousness, the extraversion trait of warmth, and the conscientiousness traits of competence and achievement striving. "Interpersonal behavior" was negatively associated with the neuroticism trait of angry hostility and positively associated with the domain of agreeableness; the extraversion traits of warmth, gregariousness, and positive emotions; and the agreeableness traits of trust, altruism, compliance, and tender-mindedness. Clinical evaluations of medical students may favor personality styles that reflect positive elements of extraversion, agreeableness, and conscientiousness. The present findings raise questions regarding the validity of clinical evaluation elements in clerkship performance appraisal.


Minimizing Uniformly Convex Functions by Cubic Regularization of Newton Method.
In this paper, we study the iteration complexity of cubic regularization of Newton method for solving composite minimization problems with uniformly convex objective. We introduce the notion of second-order condition number of a certain degree and justify the linear rate of convergence in a nondegenerate case for the method with an adaptive estimate of the regularization parameter. The algorithm automatically achieves the best possible global complexity bound among different problem classes of uniformly convex objective functions with Hölder continuous Hessian of the smooth part of the objective. As a byproduct of our developments, we justify an intuitively plausible result that the global iteration complexity of the Newton method is always better than that of the gradient method on the class of strongly convex functions with uniformly bounded second derivative.


HES1 inhibits adipogenesis of porcine mesenchymal stem cells via transcriptional repression of FAD24.
Adipogenesis, the development from preadipocytes or mesenchymal stem cells (MSCs) to mature adipocytes, is regulated by a network of signaling pathways and transcription factors. The involvement of Notch signaling and its effector HES1 in adipogenesis has been investigated in several studies with conflicting results. The underlying mechanisms remain unclear because of the lack of information about HES1 target genes during adipocyte differentiation. As a novel gene transiently up-regulated in early adipogenesis, FAD24 functions as a positive regulator of adipocyte differentiation in both preadipocytes and MSCs. In the present study, we report that the expression level of FAD24 is inversely associated with that of HES1 in porcine MSCs after adipogenic induction. Enforced overexpression of HES1 in MSCs during the early stage of adipogenesis significantly repressed the transcription of FAD24 (P < 0.01) and the other pro-adipogenic genes (P < 0.05), resulting in reduced intracellular lipid accumulation. Sequence analysis showed that porcine FAD24 harbors an evolutionarily conserved HES1 binding site in its proximal promoter region. Functional HES1, but not its dominant-negative mutant, markedly reduced the promoter activity of FAD24 (P < 0.01). Site-directed mutation and chromatin immunoprecipitation further confirmed that HES1 inhibits FAD24 transcription by direct binding to the promoter. Taken together, we identified FAD24 as a novel downstream target of HES1 during adipogenesis. Our data suggest that HES1-mediated repression of FAD24 transcription at the early stage of adipocyte differentiation may contribute to the impaired adipogenesis induced by the Notch-HES1 signaling pathway.


Use of quality-of-life instruments for people living with HIV: a global systematic review and meta-analysis.
Due to the effectiveness of combined antiretroviral therapy and its growing availability worldwide, most people living with HIV (PLHIV) have a near-normal life expectancy. However, PLHIV continue to face various health and social challenges that severely impact their health-related quality-of-life (HRQoL). The UNAIDS Global AIDS Strategy discusses the need to optimize quality-of-life, but no guidance was given regarding which instruments were appropriate measures of HRQoL. This study aimed to review and assess the use of HRQoL instruments for PLHIV. We conducted a global systematic review and meta-analysis, searching five databases for studies published between January 2010 and February 2021 that assessed HRQoL among PLHIV aged 16 years and over. Multivariable regression analyses were performed to identify factors associated with the choice of HRQoL instruments. We examined the domains covered by each instrument. Random-effects meta-analysis was conducted to explore the average completion rates of HRQoL instruments. From 714 publications, we identified 65 different HRQoL instruments. The most commonly used instruments were the World Health Organization Quality-of-Life- HIV Bref (WHOQOL-HIV BREF)-19%, Medical Outcome Survey-HIV (MOS-HIV)-17%, Short Form-36 (SF-36)-12%, European Quality-of-Life Instrument-5 Dimension (EQ-5D)-10%, World Health Organization Quality-of-Life Bref (WHOQOL BREF)-8%, Short Form-12 (SF-12)-7% and HIV/AIDS Targeted Quality-of-Life (HAT-QOL)-6%. There were greater odds of using HIV-specific instruments for middle- and low-income countries (than high-income countries), studies in the Americas and Europe (than Africa) and target population of PLHIV only (than both PLHIV and people without HIV). Domains unique to the HIV-specific instruments were worries about death, stigma and HIV disclosure. There were no significant differences in completion rates between different HRQoL instruments. The overall pooled completion rate was 95.9% (95% CI: 94.7-97.0, I2 = 99.2%, p < 0.01); some heterogeneity was explained by country-income level and study type. A wide range of instruments have been used to assess HRQoL in PLHIV, and the choice of instrument might be based on their different characteristics and reason for application. Although completion rates were high, future studies should explore the feasibility of implementing these instruments and the appropriateness of domains covered by each instrument.


Survival and arrhythmic risk among ischemic and non-ischemic heart failure patients with prophylactic implantable cardioverter defibrillator only therapy: A propensity score-matched analysis.
Concerns about the efficacy of prophylactic ICD in non-ischemic cardiomyopathy (NICM) heart failure (HF) patients are still present. We aimed to assess whether survival and arrhythmic risk were different among ischemic cardiomyopathy (ICM) and NICM ICD-only patients, along with specific predictors for mortality. HF patients undergoing ICD-only implant were extracted from the nationwide multicenter UMBRELLA registry. Arrhythmic events were collected by remote monitoring and reviewed by a committee of experts. 782 patients (556 ICM; 226 NICM) were recruited: mean ejection fraction of 26.6%; 83.4% in NYHA class II-III; mean QRS duration of 108.9 ms (only 14.9% with QRS > 130 ms). After 4.35 years of mean follow-up, all-cause mortality rate was 4.2%/year. In propensity-score (PS) analysis no survival differences between ICM and NICM subgroups appeared (mortality rates: 19.4% vs. 20%, p = 0.375). Age (hazard ratio [HR] = 1.02, p = 0.009), diabetes (HR = 2.61, p ≤ 0.001), chronic obstructive pulmonary disease (HR = 2.13, p = 0.002), and previous HF (HR = 2.28, p = 0.027) correlated with increased mortality for the entire population, however atrial fibrillation (AF) (HR = 2.68, p = 0.002) and chronic kidney disease (HR = 3.74, p ≤ 0.001) emerged as specific predictors in NICM patients. At follow-up, 134 patients (17.1%) were delivered a first appropriate ICD therapy (5.1%/year) without significant differences between ICM and NICM patients in the PS analysis (17.6% vs. 15.8%, p = 0.968). ICD shocks were associated with a higher mortality (HR = 2.88, p < 0.001) but longer detection windows (HR = 0.57, p = 0.042) correlated with fewer appropriate therapies. Mortality and arrhythmia free survival is similar among ICM and NICM HF patients undergoing ICD-only implant for primary prevention strategy.


Fetal breathing patterns in intrauterine growth retardation.
Fetal breathing movements were studied with real time ultrasound in 21 normal fetuses and 30 fetuses born small-for-dates (less than the 5th centile). The events of the study period were recorded on punched paper tape which was subjected to computer analysis. In the normal group the percentage time of breathing was 54 +/- 12.7 (mean +/- SD). The breath to breath interval was 1.34 +/- 0.25 seconds and the coefficient of variation of this interval was 49.6 +/- 7.7 per cent. In 17 of the small-for-dates group amount of breathing was reduced with short breathing episodes and long apnoea intervals. In the other 13 patients in the small-for-dates group the coefficient of variation for the breath to breath interval was significantly reduced (39.6 +/- 7.9 per cent, p less than 0.01).


Platelet serotonin release in rheumatoid arthritis: a study in food-intolerant patients.
Serotonin and 5-hydroxyindoleacetic acid levels in platelet-rich plasma were determined in serial samples obtained before and up to 6 h after food-challenge in 7 patients showing inflammation of the joints after ingestion of certain foods. Exacerbation of arthritis was associated with a fall in serotonin levels and a subsequent increase in 5-hydroxyindoleacetic acid. These data suggest that serotonin may be released from platelets during food challenges and that platelet serotonin release may contribute to joint inflammation.


Localization of lactoferrin and nonspecific cross-reacting antigen in human breast carcinomas. An immunohistochemical study using the avidin-biotin-peroxidase complex method.
A retrospective immunocytochemical study was performed on 67 human breast carcinomas to determine whether the epithelial cell-associated antigens, lactoferrin and nonspecific cross-reacting antigen (NCA), could be used as markers in the prognostic assessment of breast cancers. Fixed paraffin sections were tested with anti-lactoferrin and anti-NCA. Lactoferrin and NCA were found in 7.5% and 19% of the cases, respectively. Furthermore, the association between these two antigens in tumor cells was significant (P less than 0.05). Kappa-casein was observed in all antigen-positive cases. These antigens were observed more often in low-grade ductal carcinomas that had positive estrogen and progestin receptors, but no relationship could be established between lactoferrin or NCA and other prognostic indicators, such as histologic type and grade of the tumor, stromal elastosis, or steroid receptors. Although more antigen might have been detected in unfixed, frozen specimens, the results indicate that lactoferrin and NCA possess minimal value as epithelial cell markers and no prognostic value when detected on routinely fixed, paraffin-embedded samples.


Improved glycemic control and lower frequency of severe hypoglycemia with insulin detemir; long-term experience in 105 children and adolescents with type 1 diabetes.
To assess the effect of the insulin analog detemir on glycemic control and severe hypoglycemia in children and adolescents with type 1 diabetes. A retrospective chart analysis was performed in 105 patients with type 1 diabetes after switching to insulin detemir between 2004 and 2007. In children below 12 yr of age (n = 53), evening neutral protomin hagedorn (NPH) insulin was replaced by insulin detemir if therapeutic goals were not reached and blood glucose levels were unpredictable or hardly controllable. In adolescents above 12 yr of age (n = 52), insulin detemir was started when changing to intensified insulin therapy. In children below 12 yr of age, hemoglobin A1c (HbA1c) at start was 8.3 +/- 0.8% and after 12 months of treatment with insulin detemir significantly lowered (7.6 +/- 0.6%, p < 0.001). In the age-group above 12 yr of age at the start of the study, the improvement of HbA1c after 12 months of treatment was less pronounced (8.0 +/- 1.2 vs. 7.6 +/- 1.0%) but still significant (p < 0.01). The risk for severe hypoglycemia was significantly decreased compared with patients attending the outpatient clinic between 1995 and 2003 (4.8/100 patient years vs. 7.6/100 patient years, p = 0.003). From the beginning to the end of the follow-up period, body mass index dropped significantly in children below 12 yr of age but no effect was observed in adolescents. Use of insulin detemir allows a safe nocturnal glycemic control in children and adolescents with type 1 diabetes and is associated with significantly improved HbA1c levels and fewer severe hypoglycemic events. This makes insulin detemir a most valuable new tool for the treatment of children and adolescents with type 1 diabetes.


A comparative study of economical separation and aggregation properties of biologically capped and thiol functionalized gold nanoparticles: selecting the eco-friendly trojan horses for biological applications.
We are presenting facile bio-fabrication of extremely stable gold nanoparticles (GNPs) using medicinal plant Azadirachta indica (commonly called Neem) and its comparison with most commonly used glutathione (GSH) protected GNPs in terms of stability under physiological conditions, seperation using density gradient centrifugation and aggregation properties in the solution. There was dual peak at 536 and 662 nm indicating the presence of non-spherical GNPs including triangles, rods and hexagons in case of A. indica mediated GNPs unlike citrate stabilized GNPs which exhibited single sharp peak. Spherical GNPs were separated from the consortium of uniquely shaped nanoparticles bio-fabricated using A. indica leaf extract using sucrose density gradient centrifugation (SDGC).To comprehend the anti-agglomeration potentials of A. indica leaf mediated GNPs and GSH-GNPs under physiological conditions, flocculation parameters (FP) were calculated and found to be least for A. indica leaf mediated GNPs, indicating their exceptional stability.


Mechanisms and models to predict a QTc effect.
Prolongation of the QT interval with consequent ventricular tachyarrhythmias may arise in the context of bradycardia (pause dependent) or may reflect sympathetic imbalances (adrenergic dependent). The normal repolarization process of ventricular myocardial cells is not entirely synchronous; some cells recover early and some later, resulting in a normal heterogeneity in refractoriness among ventricular cells during the inscription of the T wave. If the normal heterogeneity in ventricular repolarization is increased, as can occur following administration of some class IA and class III antiarrhythmic agents, then the QT interval will be prolonged. All-or-none action potentials can be evoked only in cells that have repolarized to a critical membrane potential of about -60 mV. Thus, the late-recovering cells (which terminate the T wave) may still be refractory and incapable of generating propagated action potentials while the early-recovering cells (which initiate the T wave) are fully excitable. In normal hearts, the period between repolarization of the earliest and the latest cells is insufficient to allow even very premature ventricular beats that occur early during the T wave (R-on-T phenomenon) to precipitate a sustained tachyarrhythmia. When the recovery process among ventricular cells becomes more inhomogeneous, however, as in the prolonged QT syndrome, the accompanying increased heterogeneity in ventricular repolarization and refractoriness can lead to the development of malignant ventricular arrhythmias, including torsades de pointes. Any drug that increases the dispersion of the repolarization process may prolong the QT interval and raise the potential for arrhythmias.(ABSTRACT TRUNCATED AT 250 WORDS)


Using stimulating catheters for continuous sciatic nerve block shortens onset time of surgical block and minimizes postoperative consumption of pain medication after halux valgus repair as compared with conventional nonstimulating catheters.
We prospectively tested the hypothesis that the use of a stimulating catheter improves the efficacy of continuous posterior popliteal sciatic nerve block in 100 randomized patients scheduled for elective orthopedic foot surgery. After eliciting a sciatic mediated muscular twitch at < or = 0.5 mA nerve stimulation output, the perineural catheter was advanced 2-4 cm beyond the tip of the introducer either blindly (Group C; n = 50) or stimulating via the catheter (Group S; n = 50). A bolus dose of 25 mL of 1.5% mepivacaine was followed by a postoperative patient-controlled infusion of 0.2% ropivacaine (basal infusion: 3 mL/h; incremental dose: 5 mL; lockout time: 30 min). Propacetamol 2 g IV was administered every 8 h, and opioid rescue analgesia was available if required. Catheter placement required 7 +/- 2 min in Group S and 5 +/- 2 min in Group C (P = 0.056). A significantly shorter onset time of both sensory and motor blocks was noted in Group S. No difference in quality of pain relief at rest and during motion was reported between the groups. Median (range) local anesthetic consumption during the first 48 h after surgery was 239 mL (175-519 mL) and 322 mL (184-508 mL) in Groups S and C, respectively (P = 0.002). Rescue opioid analgesia was required by 12 (25%) and 28 (58%) patients in Groups S and C, respectively (P = 0.002). We conclude that the use of a stimulating catheter results in shorter onset time of posterior popliteal sciatic nerve block, similar pain relief with reduced postoperative consumption of local anesthetic solution, and less rescue opioid consumption. This prospective, randomized, blind investigation demonstrated that the use of a stimulating catheter for continuous posterior popliteal sciatic nerve block resulted in shorter onset time of sensory and motor blocks and less local anesthetic consumption and need for rescue pain medication after elective orthopedic foot surgery compared with blind catheter advancement.