Developing a model of factors that influence meeting the needs of family with a relative in ICU.
To develop a model of factors influencing meeting family needs when a relative was admitted to the intensive care unit (ICU). Studies identify individual factors impact on the needs of family members with a relative in ICU. No studies have reported on relationships between these factors and/or the extent of influence of multiple factors on family needs. Observational, correlational, and predictive study design. Data were collected from August 2013 to June 2014 using validated scales and a demographic tool. The setting was a large tertiary referral hospital in Brisbane, Australia. Structural equation modelling was undertaken. One hundred and seventy ICU family members participated. Factors included in the developed model were consistent with the literature. Family member anxiety had direct and significant influence on ICU family needs (β = 0.21). Gender was also found to have direct influence (β = 0.19), suggesting female family members were more likely to report needs being met. Family member coping self-efficacy (β = -0.40) and family member depression (β = -0.33) were mediating variables. Interventions to meet family needs within the ICU should take into account family member levels of anxiety, depression, and coping self-efficacy with consideration of gender. Further model validation is required to confirm findings.


Relative potency of prorenoate and spironolactone in normal man.
The potency of single doses of a new aldosterone antagonist, prorenoate, in reversing the renal effects of the synthetic mineralocorticoid fludrocortisone was compared to that of spironolactone in a double-blind balanced crossover study in 12 healthy subjects. The potency of prorenoate potassium as related to elevation of the urinary log 10 10 Na/K ratio (2.69:1) and as related to potassium retention (3.75:1) was significantly higher than that of spironolactone. Prorenoate produced greater natriuresis (1.64:1) but the difference was not significant. There was evidence for a qualitative difference between spironolactone and prorenoate; the latter significantly more potent in retaining potassium than in increasing sodium excretion. The simple methodology described is based on standard bioassay principles, yielded a valid and sensitive comparison of the two drugs, and should prove useful in the evaluation of other aldosterone antagonists.


Long-term results of guided tissue regeneration therapy with non-resorbable and bioabsorbable barriers. II. A case series of infrabony defects.
The aim of this 5-year follow-up case series was to clinically and radiographically evaluate the long-term results after guided tissue regeneration (GTR) therapy of infrabony defects using non-resorbable and bioabsorbable barriers. In 12 patients with advanced chronic periodontitis 12 pairs of contralateral infrabony defects were treated. Within each patient one defect received a non-resorbable (expanded polytetrafluoroethylene [ePTFE]; control: C) and the other a bioabsorbable (polyglactin 910; test: T) barrier by random assignment. At baseline and at 6 and 60 +/- 3 months after surgery clinical parameters and standardized radiographs were obtained. Gain of bone density within infrabony defects was assessed using subtraction radiography. Eight of 12 patients were available for the 60-month reexaminations. Six and 60 +/- 3 months after GTR therapy statistically significant (P < 0.05) vertical attachment (CAL-V) gain was observed in both groups (C6:2.6 +/- 1.4 mm; C60: 1.6 +/- 1.5 mm; T6:3.0+/- 1.7 mm; T60: 3.0 +/- 0.7mm). However at 60 months, 2 infrabony defects in the control group had lost all the attachment that had been gained 6 months after therapy and a clinically relevant but statistically in significant mean CAL-V loss of 1.0 +/- 2.1 mm was observed from 6 to 60 months. The case series failed to show statistically significant differences between test and control regarding CAL-V gain 60 months after surgery. Also subtraction analysis failed to reveal statistically significant differences regarding density gain between both groups 6 and 60 months postsurgically (C6: 26.4 +/- 54.2; C60 62.8 +/- 112.7; T6: 68.7 +/- 72.8; T60. 84.1 +/- 83.6). CAL-V gain achieved after GTR therapy in infrabony defects using both non-resorbable and bioabsorbable barriers was quite stable after 5 years in 14 of 16 defects.


Movement disorders in mitochondrial diseases.
Mitochondrial diseases (MIDs) are a large group of heterogeneous disorders due to mutations in either mitochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes, the latter encoding proteins involved in mitochondrial function. A multisystem clinical picture that involves several organs, including both the peripheral and central nervous systems, is a common presentation of MID. Movement disorders, even isolated ones, are not rare. Cerebellar ataxia is common in myoclonic epilepsy with ragged red fibers (MERFF) due to mutations in the mitochondrial transfer RNA (tRNA) lysine gene, in Kearns-Sayre syndrome due to mtDNA deletions, in sensory ataxic neuropathy with dysarthria and ophthalmoplegia (SANDO) due to nuclear POLG1 gene mutations, and also in ARCA2, Friedreich's ataxia, SPG7, SCA28 and autosomal-recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) due to mutations in nuclear genes involved in mitochondrial morphology or function. Myoclonus is a key feature of MERFF, but may also be encountered in mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (MELAS), ARCA2, POLG1 mutations and Leigh syndrome. Dystonia is common in Leigh syndrome (which may be caused by 75 different genes) and in Leber hereditary ocular neuropathy (LHON) plus disease, due to mutations in mtDNA genes that encode subunits of NADH dehydrogenase, as well as in ARCA2, pantothenate kinase-associated neurodegeneration (PKAN), mitochondrial membrane protein-associated neurodegeneration (MPAN) and POLG1 mutations. Other movement disorders are rarer (such as parkinsonism, tremor, chorea). Although parkinsonism is more frequent in POLG1 mutations, and myoclonus in MERFF, most movement disorders are found either isolated or combined in numerous MIDs. The presence of associated neurological signs, whether central or peripheral, or of evocative magnetic resonance imaging (MRI) abnormalities (striatal necrosis) should prompt a search for MID. In cases of a particular clinical spectrum (LHON, MERFF, Kearns-Sayre, SANDO, SPG7, ARCA2, ARSACS), a search for the most frequently implicated mutation(s) is recommended. In other cases, muscle biopsies followed by metabolic and genetic studies may be useful for arriving at a diagnosis.


Laser in situ keratomileusis nomogram development.
There is no standard laser in situ keratomileusis (LASIK) nomogram for the Nidek EC-5000 excimer laser when used with current software versions 2.23 or 2.25. Nomogram tables developed by various EC-5000 users differ significantly from one another. We analyzed the results of our first 138 eyes treated for myopia and myopic astigmatism with the Nidek EC-5000 excimer laser, model 2b, long working distance. In addition to analyzing standard clinical outcomes, the correction values entered into the laser were compared to the achieved change in refraction for these eyes. A global nomogram parameter was created, incorporating the effect of optical zone size and patient age. After observing initial overcorrections, we elected to treat most of the eyes using a 20% reduction of the attempted spherical correction. The mean value for the attempted change in spherical equivalent refraction was -6.85 D. This correction was achieved with a standard deviation of -0.04 D at 1 month, -0.08 D at 3 months, and -0.09 D at 6 months after LASIK. The postoperative values for the uncorrected and spectacle-corrected visual acuity were similar to other published studies. However, scatterplots comparing the laser settings to achieved postoperative refractions showed a clear 20% trend toward overcorrection. This trend increased with patient age and optical zone diameter. The basic calibration values (factory standard) for software versions 2.23 and 2.25 are too aggressive for LASIK treatments. When using optical zone diameters of 6 mm and above, the spherical refraction values entered into the laser must be reduced by at least 20%. LASIK nomograms for the Nidek EC-5000 excimer laser should be specific for optical zone diameter and patient age.


Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.
To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.


Are Genetic Therapies for Epilepsy Ready for the Clinic?
In recent years, there has been a significant increase in preclinical studies to test genetic therapies for epilepsy. Some of these therapies have advanced to clinical trials and are being tested in patients with monogenetic or focal refractory epilepsy. This article provides an overview of the current state of preclinical studies that show potential for clinical translation. Specifically, we focus on genetic therapies that have demonstrated a clear effect on seizures in animal models and have the potential to be translated to clinical settings. Both therapies targeting the cause of the disease and those that treat symptoms are discussed. We believe that the next few years will be crucial in determining the potential of genetic therapies for treating patients with epilepsy.


[Heart rate response to intravenous atropine during cervical and lumbar epidural anesthesia].
The authors evaluated the effect of cervical and lumbar epidural anesthesia on the heart rate response to intravenous atropine 0.01 mg.kg-1 in conscious humans with cervical epidural anesthesia (n = 40), with lumbar epidural anesthesia (n = 15) and without epidural anesthesia (n = 25). During cervical and lumbar epidural anesthesia using 1.5% lidocaine, levels of loss of cold sensation were C3-T7 and T7-S1, respectively. Heart rate increased by 14 +/- 10% (mean +/- SD) and 20 +/- 14% after intravenous atropine 0.01 mg.kg-1 in the patients with cervical and lumbar epidural anesthesia, respectively. These magnitudes of positive chronotropic effects were significantly less as compared with those in the patients without epidural anesthesia (32 +/- 11%). Nine of 40 patients (23%) with cervical epidural anesthesia showed heart rate increases of less than 3 beats.min-1 following atropine 0.01 mg.kg-1. And 30 of 40 patients (75%) required supplementary atropine 0.01 mg.kg-1 to increase heart rate for more than 20 beats.min-1 from baseline values. The present study suggests that the heart rate response to intravenous atropine is blunted in patients during cervical and lumbar epidural anesthesia, and that a larger dose of intravenous atropine may be required to accelerate the heart rate in most patients during cervical epidural anesthesia.


Effect of intracerebroventricular administration of substance P and its hexapeptide fragment on the estrus cycle in female rats.
The purpose of the reported experiments was the study of the effects of intracerebroventricular (i.c.v.) administration of substance P (SP 1--11) and its hexapeptide C-terminal fragments SP 6--11 and (pGlu6)SP6--11 on the length of the estrus cycle. In the animals with a regular sequence of estrus aliquots of 250 pmol of the three peptides: SP 1--11, SP 6--11 and (pGlu6)SP 6--11 on the carier dextrane were infused into the left lateral cerebral ventricle through a chronically implanted cannula. For control, dextran solution in 0.9% NaCl was infused in a similar way. I.c.v. infusion of dextran in 0.9% NaCl, SP 1--11 and (pGlu6)SP 6--11 caused no significant changes in the length of the estrus cycle during which the infusion was done. Infusion of SP 6--11 prolonged the diestrus phase in most animals. This observation indicates that SP 6--11 exerted an effect on the hypothalamic mechanism controlling the secretion of gonadotropins by the hypophysis.


Effects and mechanisms of cavidine protecting mice against LPS-induced endotoxic shock.
LPS sensitized mice are usually considered as an experimental model of endotoxin shock. The present study aims to evaluate effects of cavidine on LPS-induced endotoxin shock. Mice were intraperitoneally administrated with cavidine (1, 3 and 10mg/kg) or DEX (5mg/kg) at 1 and 12h before injecting LPS (30mg/kg) intraperitoneally. Blood samples, liver, lung and kidney tissues were harvested after LPS injection. The study demonstrated that pretreatment with cavidine reduced the mortality of mice during 72h after endotoxin injection. In addition, cavidine administration significantly attenuated histological pathophysiology features of LPS-induced injury in lung, liver and kidney. Furthermore, cavidine administration inhibited endotoxin-induced production of pro-inflammatory cytokines including TNF-α, IL-6 and HMGB1. Moreover, cavidine pretreatment attenuated the phosphorylation of mitogen-activated protein kinase primed by LPS. In summary, cavidine protects mice against LPS-induced endotoxic shock via inhibiting early pro-inflammatory cytokine TNF-α, IL-6 and late-phase cytokine HMGB1, and the modulation of HMGB1 may be related with MAPK signal pathway.


Effect of light and incubation temperature on production by species of Fusarium of metabolites toxic to larvae of Tenebrio molitor L.
Larvae of Tenebrio molitor L., Gembloux strain, race F, having an initial weight of 10 mg were reared for 4 weeks at 27 +/- 0.25 degrees C 65 +/- 5% relative humidity on rye seed incubated with single isolates of four strains of Fusarium. The fungi had been cultured in total darkness or in constant light at a temperature of 8, 14, 20 or 24 degrees C. Two isolates of Fusarium poae (Peck). Wollenw. (7450 and 7452) retarded growth more than the third isolate of this species or than the isolate of Fusarium accuminatum Ell. & Ev. Nutritional value of rye seed decreased with increasing temperature, but declined to a larger extent when Fusarium species were present than when they were absent. The results suggest that changes in weight and mortality of larvae are good criteria for determining toxicity of fungal metabolites in Insects.


Nephrographic density and renal diatrizoate content in experimental acute renal failure.
Reversible acute renal failure (ARF) was induced in rats by intramuscular injection of glycerol. In these animals and controls, renal concentrations of 125I-labelled sodium diatrizoate, injected intravenously in doses similar to those used clinically, were compared with the density of the nephrogram, subjectively assessed under carefully controlled conditions. Though a good statistical correlation existed between renal diatrizoate concentration and nephrographic density, individual variation was wide. At any given level of renal iodine concentration, nephrograms were judged to be denser in ARF than in controls. This was not due to differences in whole-body opacification or renal size, but was partly explained by the greater visibility of renal outlines on plain films in ARF. However, though at all doses of diatrizoate renal iodine concentrations were higher in controls, differences in nephrographic density were in general difficult to detect.


Transposable elements in filamentous fungi.
The past 10 years have been productive in the characterization of fungal transposable elements (TEs). All eukaryotic TEs described are found including an extraordinary prevalence of active members of the pogo family. The role of TEs in mutation and genome organization is well documented, leading to significant advances in our perception of the mechanisms underlying genetic changes in these organisms. TE-mediated changes, associated with transposition and recombination, provide a broad range of genetic variation, which is useful for natural populations in their adaptation to environmental constraints, especially for those lacking the sexual stage. Interestingly, some fungal species have evolved distinct silencing mechanisms that are regarded as host defense systems against TEs. The examination of forces acting on the evolutionary dynamics of TEs should provide important insights into the interactions between TEs and the fungal genome. Another issue of major significance is the practical applications of TEs in gene tagging and population analysis, which will undoubtedly facilitate research in systematic biology and functional genomics.


High fat diet activates adult mouse lung stem cells and accelerates several aging-induced effects.
High fat diet (HFD) decreases the lifespan of mice, and is a risk factor for several human diseases. Here, we investigated the effects of a HFD on lung epithelial and stem cells and its interaction with aging. Young and old mice were fed with either a standard diet (SD) or a HFD then their trachea and lung were examined for histological changes, inflammation, and mitochondrial function. Their stem cell function was examined using the in vitro organoid/colony forming efficiency (CFE) assay. Aging reduced the number of tracheal basal and alveolar type-2 (AT2) cells. HFD significantly increased the number of AT2 cells. Aging also caused a significant increase in lung inflammation, and HFD caused a similar increase, in young mice. Aging reduced mitochondrial mass and function, and increased reactive oxygen species. In young mice, HFD caused mitochondrial changes similar to the aging-induced changes. Organoid culture of tracheal and lung epithelial cells collected from both young and old HFD-fed mice showed higher CFE compared to SD-fed mice. Switching the HFD to low calorie/fat diet (LCD) efficiently reversed several of the HFD-induced effects. Thus, HFD induces several histological, inflammatory, and functional changes in the lung, and exacerbates the aging-induced lung inflammation and mitochondrial deterioration. LCD can reverse many of the HFD-induced effects.


Anti-CD20 monoclonal antibody treatment in 6 patients with therapy-refractory chronic graft-versus-host disease.
Chronic graft-versus-host disease (cGVHD) is an important determinant of long-term morbidity and mortality in allogeneic stem cell transplantation patients. Because cGVHD has clinical, histologic, and laboratory findings of autoimmune diseases and anti-B-cell therapy has shown efficacy in autoimmune diseases, we hypothesized that monoclonal anti-CD20 antibody therapy might improve patients with cGVHD. We treated 5 men and 1 woman with therapy-refractory extensive cGVHD with anti-CD20 monoclonal antibody. Intravenous infusion was given at a weekly dose of 375 mg/m(2) for 4 weeks. In case of incomplete clinical response, additional courses of 4 weeks were given. Five patients responded to treatment with marked clinical, biochemical, and histologic improvement. One patient failed to respond. Anti-CD20 monoclonal antibody seems to be effective in cGVHD. A controlled trial is mandatory to confirm these results. The outcome of this study suggests a participating role of B cells in the pathogenesis of cGVHD.


Influence of Dental Pulp Harvesting Method on the Viability and Differentiation Capacity of Adult Dental Pulp-Derived Mesenchymal Stem Cells.
To compare two pulp harvesting methods for stem cell expansion, namely, conservative pulpotomy and pulpectomy from exodontia. Ten freshly extracted sound third molars from five patients were selected. Five were used in the control group, where pulp harvesting was performed by exodontia and the remaining teeth were used in the test group, where the pulp was harvested by conservative pulpotomy (preserving the tooth). This was a split-mouth design study, where a third molar from one side was randomly allocated into the test group and the contralateral tooth in the control group. After pulp harvesting, the following evaluations were performed: cell morphology, sterility test, immunophenotyping, differentiation assays, first pass live cell counts, time to cryopreservation, and total number of expanded cells at the end of the fourth pass. Regarding morphology, the cells from both groups presented a fibroblastic phenotype. All samples were sterile. Immunophenotyping demonstrated a positive expression for CD105, CD90, and CD73 and negative expression for CD45 in both groups. Differentiation assays were positive for osteogenic and chondrogenic differentiation in both groups. Regarding live cell counts in the first passage, the control group had 95.8% live cells in the total count and the test group 91.2% (p < 0.05). The time required for cryopreservation was equivalent in both groups 51.6 days and 52.6 days, respectively (p > 0.05). The total number of cells at the end of the fourth passage was 5,286,782 and 5,736,862, respectively (p > 0.05). These results suggest that adult stem cell harvesting from conservative pulpotomy is as effective as the traditional exodontia-based method.


Obstructive sleep apnea pretreatment and posttreatment in symptomatic children with congenital craniofacial malformations.
Obstructive sleep symptoms are common in children with craniofacial malformations (CFM). However objective data about obstructive sleep apnea (OSA) is still limited. The aims of this study were to investigate the frequency of OSA in symptomatic children with CFM and to determine improvement in severity of OSA after treatment. Symptomatic children with CFM referred for a diagnostic polysomnogram (PSG) were identified. Obstructive sleep apnea was defined as an apnea/hypopnea index (AHI) ≥ 1, with moderate/severe OSA as an AHI ≥ 5. Overall, 151 symptomatic children were identified; 87% were diagnosed with OSA, of whom 24% had moderate-to-severe OSA. Children with syndromic CFM, compared to non-syndromic CFM, were more likely to have an AHI ≥ 5 (syndromic 33% vs. non-syndromic 15%, p = 0.02). Of the 131 children with OSA, 64 were treated and 32 returned for a posttreatment PSG, with 22 treated with either positive airway pressure (PAP) or adenotonsillectomy (AT). Children treated with PAP demonstrated a decrease in AHI from 6.2 to 3.5 (p = 0.057) and an increase in SpO2 from 89.1% to 91.1% (p = 0.091). There were no significant improvements for those in the AT group for either AHI (2.5 to 1.8, p = 0.19) or SpO2 (90.4% to 91.3%, p = 0.46). Normalization of the AHI (AHI < 1) occurred in only one child in each group (7% and 14% of the PAP and AT groups, respectively). The vast majority of children with CFM referred for OSA evaluation are found to have objective evidence of OSA and a quarter of children have moderate-to-severe OSA. It is likely that many children with underlying OSA are not identified and referred for evaluation. Residual OSA after treatment is common in children with CFM.


The influence of methylmercury on the nitric oxide production of alveolar macrophages.
Mercury is a global pollutant considered to be a persistent bioaccumulative and toxic chemical. Humans may be exposed to organic forms of mercury by either inhalation, oral, or dermal routes. Methylmercury is more toxic to living organisms than the inorganic forms. In this study, we attempted to elucidate the altered functions of alveolar macrophage including nitric oxide production after methylmercury exposure. Treatment of 7 muM methylmercury for 24 h inhibited lipopolysaccharide-induced nitric oxide and nitric oxide synthase production of alveolar macrophages. The addition of H-89 (PKA inhibitor) significantly decreased the methylmercury inhibition of lipopolysaccharide-mediated nitric oxide production. We found the cell had a calcium-dependent adenylate cyclase, and MeHg could inhibit the phosphorylation of extracellular-signal regulated kinase (ERK). Because methylmercury could increase the intracellular calcium ion concentration, it might activate the adenylate cyclase by increasing [Ca(2+)](i). Though the interaction of methylmercury with the immune system has been studied by several investigators, the actual mechanisms underlying these interactions are still poorly understood. We discovered that methylmercury could activate protein kinase A, which in turn would inhibit the activation of Raf-1-ERK and so inhibit the release of nitric oxide.


An Innovative Therapeutic Option for the Treatment of Skeletal Sarcomas: Elimination of Osteo- and Ewing's Sarcoma Cells Using Physical Gas Plasma.
Osteosarcoma and Ewing's sarcoma are the most common malignant bone tumors. Conventional therapies such as polychemotherapy, local surgery, and radiotherapy improve the clinical outcome for patients. However, they are accompanied by acute and chronic side effects that affect the quality of life of patients, motivating novel research lines on therapeutic options for the treatment of sarcomas. Previous experimental work with physical plasma operated at body temperature (cold atmospheric plasma, CAP) demonstrated anti-oncogenic effects on different cancer cell types. This study investigated the anti-cancer effect of CAP on two bone sarcoma entities, osteosarcoma and Ewing's sarcoma, which were represented by four cell lines (U2-OS, MNNG/HOS, A673, and RD-ES). A time-dependent anti-proliferative effect of CAP on all cell lines was observed. CAP-induced alterations in cell membrane functionality were detected by performing a fluorescein diacetate (FDA) release assay and an ATP release assay. Additionally, modifications of the cell membrane and modifications in the actin cytoskeleton composition were examined using fluorescence microscopy monitoring dextran-uptake assay and G-/F-actin distribution. Furthermore, the CAP-induced induction of apoptosis was determined by TUNEL and active caspases assays. The observations suggest that a single CAP treatment of bone sarcoma cells may have significant anti-oncogenic effects and thus may be a promising extension to existing applications.


Combination treatment of bortezomib and epirubicin increases the expression of TNFRSF10 A/B, and induces TRAIL-mediated cell death in colorectal cancer cells.
Colorectal cancer is one of the most common cancers worldwide, affecting the colon and rectum. A major problem in the treatment of colorectal cancer is acquired chemoresistance, including resistance against death receptor-induced apoptosis. Therefore, investigating new biomarkers for the treatment of the disease and sensitization strategies against TRAIL might be of high clinical importance. TNFRSF10A/B are known as death receptors for TRAIL-induced apoptotic cell death. In this study, we used multiple bioinformatic tools and experimental analyses to investigate the role of TRAIL receptors TNFRSF10A and TNFRSF10B in colorectal cancer. We also identified the potential effect of bortezomib and epirubicin in the induction of TRAIL-mediated apoptotic cell death. Here, we showed that TNFRSF10 A/B expressions are upregulated in various tumor types, including COAD, and its high expression is decreased with the different clinicopathological parameters in COAD. We also found an association between TNFRSF10 A/B expression and tumor molecular subtypes. We further detected the association between the expression of TNFRSF10 A/B and immune cell tumor infiltration, including B cells, CD8+ T cells, neutrophils and dendritic cells. In addition, we showed that combining bortezomib and epirubicin treatment leads to the upregulation of TNFRSF10 A/B in colorectal cancer cells in vitro. The increase in the expression of death receptors was correlated with higher active caspase-3 levels following the incubation of cells with recombinant TRAIL protein, which is a ligand for TNFRSF10 A/B receptors. Our results suggest that TNFRSF10 A/B may be a marker to differentiate tumor molecular subtypes in colorectal cancer. The expression of TNFRSF10 A/B may be associated with the recruitment of immune cells into tumors and the development of tumor suppression. The combination of bortezomib and epirubicin treatment might sensitize colorectal cancer cells to TRAIL-induced apoptosis via the upregulation of death receptor.


Anatomical and Morphological Features of the Fetal Human Pancreaticobiliary Ductal Union.
To investigate pancreaticobiliary ductal anatomy during developmental stages, gallbladders, common bile ducts, pancreatic ducts and their interface with the duodenum were studied in 36 human fetuses between 4-6 weeks postconceptual age were studied. For histological examination, sections were cut continuously from the paraffin-embedded tissue block and stained with hematoxylin and eosin. The expression of proliferating cell nuclear antigen in the gallbladder was examined with immunohistochemistry. Among 36 cases, three shapes of the greater duodenal papilla were found: hemispheroid (58.1%), circular cylinder (25%), and flat shape (16.9%). For the location of the greater duodenal papillas, more than half (69.4%) of the cases were in the middle descendant duodenum. Seven cases (19.4%) were in the lower descendant duodenum. Three cases (8.3%) were in the upper descendant duodenum, and one (2.9%) was in the distal descending part of duodenum. There were four types of the pancreaticobiliary ductal union: "Y" in 24 cases(66.7%), "U" in 4 cases (11.1%),"V" in 7 cases (19.4%), and pancreaticobiliary maljunction in 1 case (2.8%). For patients with congenital bile duct dilation and Biliary cancer, the positive cells of proliferating cell nuclear antigen were increased significantly (P < 0.05). Different types in pancreaticobiliary ductal union investigated in this study may provide clues for pathogenesis and clinical treatment of pancreaticobiliary maljunction.


The Role of HOTAIR/miR-148b-3p/USF1 on Regulating the Permeability of BTB.
Homeobox transcript antisense intergenic RNA (HOTAIR), as a long non-coding RNA (lncRNA), has been considered to play critical roles in the biological properties of various tumors. The purposes of this study were to investigate the role and possible molecular mechanisms of HOTAIR in regulating the permeability of blood tumor barrier (BTB) in vitro. Our present study elucidated that the expressions of HOTAIR and upstream stimulatory factor 1 (USF1) was up-regulated, but miR-148b-3p was down-regulated in glioma microvascular endothelial cells (GECs). Knockdown of HOTAIR could increase the permeability of BTB as well as down-regulated the expressions of tight junction related proteins ZO-1, occludin, claudin-5, but up-regulated miR-148b-3p expressions in GECs. Meanwhile, dual-luciferase reporter assays demonstrated that HOTAIR was a target RNA of miR-148b-3p. Furthermore, overexpression of miR-148b-3p increased the permeability of BTB by down-regulating the expressions of tight junction related proteins and USF1 in GECs, and vice versa. And further result revealed USF1 was a target of miR-148b-3p. Silence of USF1 increased the permeability of BTB duo to their interaction with the promoters of ZO-1, occludin, and claudin-5 in GECs. Taken together, our finding indicated that knockdown of HOTAIR increased BTB permeability via binding to miR-148b-3p, which further reducing tight junction related proteins in GECs by targeting USF1. Thus, HOTAIR will attract more attention since it can serve as a potential target of drug delivery across BTB and may provide novel strategies for glioma treatment.


Acute abdomen. When to operate immediately and when to observe.
When to operate immediately, when to observe, and when not to operate at all represent major challenges in the management of a child with an acute abdomen. This article is an overview of the subject from symptom to diagnosis, evaluation, and preparation for the surgical intervention. Tables provide examples of conditions requiring prompt surgical intervention and relative surgical urgency; pathologies suitable for (initial) nonsurgical management; and clinical pictures where surgical intervention is not indicated. Factors that influence the timing of operation are provided, as is the differential diagnosis between intestinal strangulation and obstruction. Brief notes highlight four important causes of acute abdomen in children acute appendicitis, malrotation with volvulus, Meckel's diverticulum, and intussusception. These as well as other intraabdominal pathologies are illustrated by means of surgical photographs. The acute abdomen is a clinical diagnosis. Other diagnostic modalities have merely supporting roles. The decision to operate is based primarily on the results of a good history and thorough physical examination(s).


Cardiac myocyte differentiation: the Nkx2.5 and Cripto target genes in P19 clone 6 cells.
Genetic evidence has implicated several genes as being critical for the development of cardiomyocytes. Whereas a few of the targets of these genes and the pathways they constitute are known the majority of targets and the interrelationships of the pathways involved still remains largely unknown. The power of high-throughput analytical techniques like microarrays and real-time RT-PCR combined with the ability to selectively silence specific mRNA in model tissue culture systems can begin to fill in these gaps and increase our understanding of the molecular mechanisms of cell commitment and terminal differentiation. We have used microarray analysis and siRNA directed against the cardiac-specific transcription factor Nkx2.5 and one of its targets Cripto in P19 clone 6 (P19Cl6) cells to identify potential targets for these genes. We demonstrate Nkx2.5 affects genes that have been shown to be controlled by the canonical Wnt or TGFbeta/BMP signaling pathways. We also show that Cripto can regulate the critical stem cell gene Nanog and two Oct 4-regulated genes: Dppa2 and 4. Cripto also affects the formation of nitric oxide, a small signaling molecule that has been reported to be important for growth and development of cardiac and smooth muscle. It affects the nitric oxide system by regulating genes that control the levels of nitric oxide synthase mRNA concentration as well as the activation and bioavailability of the protein.


Metaproteomic Analysis of Nasopharyngeal Swab Samples to Identify Microbial Peptides in COVID-19 Patients.
During the COVID-19 pandemic, impaired immunity and medical interventions resulted in cases of secondary infections. The clinical difficulties and dangers associated with secondary infections in patients necessitate the exploration of their microbiome. Metaproteomics is a powerful approach to study the taxonomic composition and functional status of the microbiome under study. In this study, the mass spectrometry (MS)-based data of nasopharyngeal swab samples from COVID-19 patients was used to investigate the metaproteome. We have established a robust bioinformatics workflow within the Galaxy platform, which includes (a) generation of a tailored database of the common respiratory tract pathogens, (b) database search using multiple search algorithms, and (c) verification of the detected microbial peptides. The microbial peptides detected in this study, belong to several opportunistic pathogens such as Streptococcus pneumoniae, Klebsiella pneumoniae, Rhizopus microsporus, and Syncephalastrum racemosum. Microbial proteins with a role in stress response, gene expression, and DNA repair were found to be upregulated in severe patients compared to negative patients. Using parallel reaction monitoring (PRM), we confirmed some of the microbial peptides in fresh clinical samples. MS-based clinical metaproteomics can serve as a powerful tool for detection and characterization of potential pathogens, which can significantly impact the diagnosis and treatment of patients.


[Are symbolic behaviour and neuroplasticity an example of gene-culture coevolution?].
The brain size in the Homo genus not only has not increased during the last 150,000 years but has also experienced a slight reduction in the last 35,000 years. This reduction coincides with the generalization of the symbolic culture that was most likely established during the Upper Palaeolithic. Therefore, the cognitive capacities characteristic in the Homo sapiens could be due to structural and functional changes during the brain evolution, rather than an increase of the brain size. Dependence of symbolic culture probably required an increase of the learning and memory skills, thus demanding, at the same time, an improvement of neuroplasticity. The epsilon3 and epsilon2 alleles of the apolipoprotein E seem to contribute to a better synaptic repairing, in relation to the ancestral epsilon4 allele. Mutation leading to the epsilon3 allele occurred between 220,000 and 150,000 years ago. Its selection and expansion may have continued until a relatively recent period that coincides with the emergence and expansion of the complex symbolic culture. Other factors favouring neuroplasticity, such as certain polymorphisms and the expression increase of certain proteins as reelin, could also have been selected. Emergence of the symbolic behaviour and increase of its deriving technical and social complexity could have made an intense selective pressure leading to a selection of genes that induced an improvement in neuroplasticity. This would constitute an example of gene-culture coevolution.


Research advances of nanomaterials for the acceleration of fracture healing.
The bone fracture cases have been increasing yearly, accompanied by the increased number of patients experiencing non-union or delayed union after their bone fracture. Although clinical materials facilitate fracture healing (e.g., metallic and composite materials), they cannot fulfill the requirements due to the slow degradation rate, limited osteogenic activity, inadequate osseointegration ability, and suboptimal mechanical properties. Since early 2000, nanomaterials successfully mimic the nanoscale features of bones and offer unique properties, receiving extensive attention. This paper reviews the achievements of nanomaterials in treating bone fracture (e.g., the intrinsic properties of nanomaterials, nanomaterials for bone defect filling, and nanoscale drug delivery systems in treating fracture delayed union). Furthermore, we discuss the perspectives on the challenges and future directions of developing nanomaterials to accelerate fracture healing.


[Laser treatment of benign prostatic hypertrophy: the correlation of histologic results to nuclear magnetic resonance imaging].
Minimally invasive treatments for benign prostatic hyperplasia (BPH) are currently very controversial. Nd:YAG laser transurethral thermocoagulation of the prostate is the technique most frequently used. The objective of this study was to assess the correlation between the morphological effects observed and the changes visible on magnetic resonance imaging during this type or treatment in the human prostate, in order to evaluate the tissue effects obtained according to the power and the interaction time applied. In 10 patients requiring radical prostatectomy for urological cancer, visual laser ablation of the prostate (VLAP) was performed during the 10 days preceding the radical operation (range: 1 to 9 days). The entire gland was submitted to pathological examination in order to correlate the histological result with contrast magnetic resonance imaging performed in 6 patients, using a standard transrectal coil, 12 to 24 hours before complete resection of the prostate. The morphological examination showed zones of periurethral necrosis of variable volume, accompanied by extensive peripheral haemorrhage, containing vessels with a partially obliterated lumen. Contrast magnetic resonance imaging (T1) showed that laser-induced lesions had a low density appearance and were perfectly demarcated with peripheral heterogeneous and hyperdense zones. In contrast with the experimental investigations performed to date, we demonstrated a clearly delayed tissue effect. Our experience demonstrates that a period of several hours between laser treatment and removal of the operative specimen is not sufficient to evaluate the extent of laser-induced lesions. High resolution magnetic resonance imaging with a standard transrectal coil, sometimes combined with a multiple coil, is very valuable to assess the effects of laser.


Effect of crocetin added to IVM medium for prepubertal goat oocytes on blastocyst outcomes after IVF, intracytoplasmic sperm injection and parthenogenetic activation.
Crocetin is an active constituent of saffron recently used as antioxidant for embryo culture. The aim of this study was to test the effect of crocetin added in the in vitro maturation (IVM) of prepubertal goat oocytes on the embryo development after in vitro fertilization (IVF), intracytoplasmic sperm injection (ICSI) and parthenogenetic activation (PA). Cumulus-oocyte complexes (COCs) were released from slaughterhouse ovaries of prepubertal goats and in vitro matured in supplemented TCM 199 medium during 24 h without (control group) and with crocetin. In Experiment 1, we evaluated the effect of the IVM supplementation with 0 μM (control), 0.5 μM, 1 μM and 2 μM of crocetin on the blastocyst development after IVF. No significant differences were obtained on blastocyst formation among groups (12, 7, 10, 11%; respectively). Although the blastocyst total cell number was higher in 1 μM crocetin group (150.7 cells) compared to the control (105.5), 0.5 μM (116.2) and 2 μM (93.7) crocetin groups, no significant differences were detected. In experiment 2, we assessed the effect of 1 μM crocetin supplementation in the IVM medium on the oocyte GSH level, ROS level and mitochondrial activity. ROS was significantly higher in the control than in the crocetin group (P < 0.05), but no differences in GSH level and mitochondrial activity were observed. In experiment 3, we evaluated the effect of 1 μM crocetin on the blastocyst development of oocytes after ICSI and PA. No statistical differences were found on blastocyst rate or cell number. However, compared with control, crocetin groups led to higher cleavage (59 vs. 67%, respectively, P = 0.09) and blastocyst rates (19 vs. 12%, respectively; P = 0.12) after ICSI. Although crocetin reduced ROS levels in prepubertal goat oocytes, it did not have a significant effect on oocyte embryo developmental competence.


Leakage Source Localization Method for Aerospace Composite Structures Based on U-Array Wave Velocity-Compensated Beamforming.
Composite materials have been widely used in spacecraft structures. Due to the harsh environment in space, gas leakage will occur in the structure, so it is necessary to locate the leakage position in time. In this paper, a beamforming localization method based on a U-shaped sensor array is studied. The array can be divided into two subarrays, which can orientate the direction of leakage sources, respectively. To solve the problem of uneven wave velocity caused by the anisotropy of composite materials, this method modifies the relationship between wave velocity and direction and combines it with the dispersion curve to select a filtering frequency band to reduce the influence of dispersion. The experiment simulates vacuum leakage by pumping holes with a diameter of 3 mm with a vacuum pump. The results show that the U-shaped array beamforming algorithm proposed in this paper can obtain a positioning error of 2.21 cm, which provides a new idea for the structural health detection of spacecraft.


Enteric adenoviruses.
The 41 serotypes of human adenoviruses are classified into six subgenera (A-F) with different tropisms. Enteric infections are caused in children by serotypes Ad40 and Ad41 of subgenus F. Serotypes Ad40 and Ad41 transform embryonic cells but cannot induce tumours in newborn hamsters. They differ from all other (established) human adenoviruses by being unable to replicate in conventional cell cultures. Ad40 and Ad41 grow in 293 cells (human embryonic kidney cells immortalized by transfection with the E1A, E1B regions of Ad5). In spite of the difficulty of isolating Ad40 and Ad41 they can be directly identified in stools by enzyme-linked immunosorbent assay (ELISA) and solid-phase immuno-electron microscopy. The amount of viral DNA in stool preparations is sufficient for identification by DNA restriction or dot-blot analysis. Adenoviruses have been associated with 7-17% of cases of diarrhoea in children. Ad40 and Ad41 cause diarrhoea throughout the year. Clinical features are watery stools, vomiting and moderately elevated temperature; respiratory symptoms are infrequent. The diarrhoea is protracted (mean 8.6 and 12.2 days for Ad40 and Ad41 respectively). Children with rotavirus diarrhoea vomited more frequently and had a higher temperature and diarrhoea of shorter duration. The impact of enteric adenoviruses in the aetiology of diarrhoea world-wide is not known but is accessible to investigation.


Earthquake Preparedness Among Japanese Hemodialysis Patients in Prefectures Heavily Damaged by the 2011 Great East Japan Earthquake.
The purpose of this study was to explore the factors related to earthquake preparedness in Japanese hemodialysis patients. We focused on three aspects of the related factors: health condition factors, social factors, and the experience of disasters. A mail survey of all the members of the Japan Association of Kidney Disease Patients in three Japanese prefectures (N = 4085) was conducted in March, 2013. We obtained 1841 valid responses for analysis. The health factors covered were: activities of daily living (ADL), mental distress, primary renal diseases, and the duration of dialysis. The social factors were: socioeconomic status, family structure, informational social support, and the provision of information regarding earthquake preparedness from dialysis facilities. The results show that the average percentage of participants that had met each criterion of earthquake preparedness in 2013 was 53%. Hemodialysis patients without disabled ADL, without mental distress, and requiring longer periods of dialysis, were likely to meet more of the earthquake preparedness criteria. Hemodialysis patients who had received informational social support from family or friends, had lived with spouse and children in comparison to living alone, and had obtained information regarding earthquake preparedness from dialysis facilities, were also likely to meet more of the earthquake preparedness criteria.


Milk and milk products consumption in relationship to serum lipid levels: a community-based study of middle-aged and older population in Japan.
The authors examined the association of milk and milk products consumption (MMPC) with serum lipid profiles including total cholesterol (TC), triacylglycerols (TG), HDL cholesterol (HDLC), LDL cholesterol (LDLC), and TC/HDLC ratio in a community-based sample. The study population comprised 461 men and 834 women aged 40-79 years who, in 2001, participated in an annual healthy examination and a lifestyle related survey Consumption frequency of 17 foods, including milk and milk products, was determined by a self-administered questionnaire. The participants were asked by "Do you drink cow's milk or eat milk products such as yoghurt and cheese everyday?", and two groups ("Yes" and "No") of MMPC were classified. Multiple linear regression analyses were conducted to examine the relationships between MMPC and 5 serum lipid profile levels adjusted for sex, age, body mass index (BMI), alcohol consumption, smoking, physical activity, and fat intake. Univariate and multivariate analyses indicated inverse associations of MMPC with TC, HDLC, and LDLC, and that the "Yes" group had higher adjusted means of serum TC by 7.133 mg/100 ml (p < 0.001), HDLC by 1.844 mg/100 ml (p < 0.05), LDLC by 5.459 mg/100 ml (p < 0.001). We suggested that MMPC has an association with serum lipid and lipoprotein levels and that MMPC may have an unfavorable effect on hypercholesterolaemia in the Japanese population.


Molecular epizootiology and evolution of vesicular stomatitis virus New Jersey.
Vesicular stomatitis virus (VSV) has been shown previously to be capable of undergoing rapid mutational change during sequential experimental infections in various tissue culture cell systems (J. Holland, K. Spindler, F. Horodyski, E. Grabau, S. Nichol, and S. Vandepol, Science 215:1577-1585, 1982). The present study was undertaken to determine the degree of genetic diversity and evolution of the virus under natural infection conditions and to gain insight into the epizootiology of the disease. Between 1982 and 1985, numerous outbreaks of VSV of the New Jersey serotype were reported throughout regions of the United States and Mexico. A T1 RNase fingerprint analysis was performed on the RNA genomes of 43 virus isolates from areas of epizootic and enzootic virus activity. This indicates that virus populations were genetically relatively homogeneous within successive U.S. virus epizootics. The data included virus isolates from different epizootic stages, geographical locations, host animals, and host lesion sites. In contrast, only distant genome RNA T1 fingerprint similarities were observed among viruses of the different U.S. epizootics. However, Mexican viruses isolated before or concurrent with U.S. epizootics had very similar RNA genome fingerprints, suggesting that Mexico may have been the possible origin of virus initiating recent U.S. VSV New Jersey outbreaks. Comparison of T1 fingerprints of viruses with enzootic disease areas revealed a greater extent of virus genetic diversity in these areas relative to that observed in epizootic areas. The evolutionary significance of these findings and their relationship to experimental data on VSV evolution are discussed.


Integration of troponin I phosphorylation with cardiac regulatory networks.
We focus here on the modulation of thin filament activity by cardiac troponin I phosphorylation as an integral and adaptive mechanism in cardiac homeostasis and as a mechanism vulnerable to maladaptive response to stress. We discuss a current concept of cardiac troponin I function in the A-band region of the sarcomere and potential signaling to cardiac troponin I in a network involving the ends of the thin filaments at the Z-disk and the M-band regions. The cardiac sarcomere represents a remarkable set of interacting proteins that functions not only as a molecular machine generating the heartbeat but also as a hub of signaling. We review how phosphorylation signaling to cardiac troponin I is integrated, with parallel signals controlling excitation-contraction coupling, hypertrophy, and metabolism.


Comparison of lectin binding patterns in malformed and normal human embryos and fetuses.
Altered glycosylation in the course of disease detectable by changes in lectin binding patterns has been well established for adult tissues, but only a few authors have described carbohydrate entities during normal human embryonic and fetal development. Whether alterations in carbohydrate patterns occur in human embryonic and fetal tissues, affected by malformations, remains to be investigated. We, therefore, examined human embryos and fetuses at corresponding developmental stages with and without malformations (spina bifida, exencephaly, cleft lip and cleft palate, and dysmelia) with respect to their lectin binding patterns for the lectins RCA I, PNA, WGA, SBA, SNA, Con A, and LTA. Our results demonstrated that during the development of malformations, the affected tissue sites exhibited a different carbohydrate pattern from normally developed specimens. Furthermore, tissues known to be sites of secondary malformation, accompanying the primary defect, although displaying a histologically normal appearance, also showed an altered carbohydrate pattern. This might indicate a possible general alteration in the carbohydrate pattern in the course of development of malformations in man.


Non-nucleoside inhibitors of herpesviruses.
While the treatment of herpes simplex virus with acyclovir and similar nucleoside analogues was one of the first success stories in antiviral chemotherapy, substantial unmet medical needs remain for herpesvirus diseases. In particular, the increasing numbers of immunosuppressed people due to AIDS, transplantation, cancer and aging has driven the need for improved antivirals to treat diseases caused by human cytomegalovirus (HCMV). Currently available drugs for the treatment of HCMV diseases are less than ideal agents due to issues of toxicity, modest efficacy and poor oral bioavailability. High throughput screening of large compound collections for inhibitors of specific viral enzymes or inhibition of viral growth in cell culture have identified a number of new HCMV inhibitors at several pharmaceutical companies. These compounds act by inhibition of novel molecular targets such as the viral protein kinase, viral protease and viral proteins involved in DNA cleavage/packaging. In addition, novel non-nucleoside inhibitors of the herpesvirus DNA polymerase have recently been described. This review will summarise some of these research efforts and will focus on non-nucleoside compounds that directly inhibit a viral process.


Gastric carcinoma: correlation of diagnosis based on biopsies and resection specimens with reference to the Laurén classification.
Gastric carcinomas in 382 patients were studied histologically and the results from the preoperative endoscopic biopsies were compared with those from the resected specimens. Using the Laurén classification an overall histological diagnostic agreement between the two specimens was reached in 317 cases, or 83%. The highest diagnostic agreement, 87%, was for intestinal carcinomas. For diffuse carcinomas the diagnostic agreement was 75%. The disagreement in intestinal carcinomas was mainly due to foci of undifferentiated cells and/or signet-ring cells predominating in the biopsy. The disagreement in diffuse carcinomas was mainly because glandular structures were present at the surface in some of the cases and therefore led to an erroneous diagnosis of intestinal carcinoma. In conclusion, the intestinal type of gastric carcinoma can in most cases be diagnosed correctly from an endoscopic biopsy, whereas the diagnosis of a diffuse carcinoma is less accurate until the resected specimen is available for histological study.


Reliability of force per unit cross-sectional area measurements of the first dorsal interosseus muscle.
The purpose of this study was to determine the reliability of maximum voluntary isometric force (MVIF), cross-sectional area (CSA) and force per unit CSA measures, of the first dorsal interosseus (FDI) muscle, using a custom-built dynamometer and ultrasonography. Twenty-seven participants completed MVIF and CSA measurements on two separate occasions under the same conditions. Reliability was determined using paired samples t-tests, systematic bias ratio and ratio limits of agreement (RLoA), intra-class correlation (ICC) and coefficient of variation (CV). MVIF of the FDI muscle (mean ± s; 31.8 ± 7.6 N and 31.6 ± 7.3 N) was not different between trials (P = 0.63); RLoA between trials were 1.00 ×/÷ 1.09, ICC = 0.990 and CV = 3.22%. CSA of the FDI muscle (22.6 ± 6.9 and 22.9 ± 6.9 mm²) was also not different between trials (P = 0.31); RLoA between trials were 0.98 ×/÷ 1.19, ICC = 0.979 and CV = 6.61%. Force per unit CSA was not different between trials (1.49 ± 0.43 and 1.46 ± 0.44 N·mm²; P = 0.18), RLoA were 1.02 ×/÷ 1.17, ICC = 0.985 and CV = 5.76%. The techniques used to determine MVIF and CSA of the FDI muscle were reliable and can be combined to calculate force per unit CSA.


Second harmonic generation in Dirac/Weyl semimetals with broken tilt inversion symmetry.
We theoretically investigate the second harmonic generation in tilted Dirac/Weyl semimetals with broken tilt inversion symmetry in the absence of an external magnetic field using quantum theory. An analytical formula for the second harmonic conductivity tensor is derived, and it does not depend on the chirality of Weyl node. There are two contributions to the conductivity in the low-frequency region, one coming from the intraband transitions and describing by Drude-like effects, and the other from the interband-intraband transitions due to the linear energy dispersion of Dirac/Weyl semimetals near the Dirac/Weyl points. In the high-frequency region, the appearance of prominent resonant peaks in the nonlinear conductance originates from the two-photon absorption process. It is found that Dirac/Weyl semimetals have a very high nonlinear susceptibility, and an optimal tilt of the Dirac/Weyl node for the maximum nonlinear susceptibility has been found.


The Role of ApoE Polymorphism in the Relationship between Serum Steroid Hormone Levels and Cognition in Older Chinese Adults: A Cross-Sectional Study.
Epidemiology studies have indicated an association of apolipoprotein E (ApoE) genetic polymorphism and circulating steroid hormone levels with the risk of Alzheimer's disease. The established physiologic relationship between apolipoproteins and steroid hormone indicate an important role of ApoE polymorphism in impacting the relationship between serum steroid hormones and cognition in the elderly. A total of 500 Chinese adults aged between 50 and 75 participated in this community-based cross-sectional study. Blood samples were collected in the morning for ApoE genotyping and serum parameter assessment. Cognitive performance of participants was evaluated by Montreal Cognitive Assessment test. Age, gender, educational level, smoking, and physical activity levels are factors associated with cognitive performance in this older Chinese adults. Compared to the control subjects, MCI subjects demonstrated higher serum total cholesterol, HDL-C, and estradiol status (P < 0.05). ApoE genotype difference of serum lipid profile was observed with a relatively higher mean serum triglyceride levels in ApoE2 and ApoE4 carriers (P < 0.05), and lower mean serum HDL-C level in ApoE4 carriers (P < 0.05). Memory and delayed recall ability was serum estradiol level related; and subjects with higher circulating estradiol concentration exhibited lower memory and delayed recall ability (P < 0.05). The association of serum estradiol and cortisol concentration with cognitive performance was ApoE genotypes dependent. Poor cognitive performance was observed in ApoE2 and ApoE4 carriers with higher serum estradiol level (P < 0.05). Moreover, ApoE2 and ApoE4 carriers with higher serum cortisol status demonstrated decreased language ability (P < 0.05). Multiple logistic regression analysis indicates that subjects with higher serum estradiol status may have an increased risk for MCI [OR = 2.004, 95% confidence interval (CI): 1.135, 3.540; P = 0.017]. ApoE2 carriers with higher serum steroid levels may be potentially predisposed to an increased risk of MCI (OR = 3.353; 95% CI: 1.135, 9.907; P = 0.029). Cognitive outcomes in older Chinese adults are associated with serum steroid hormone status. Higher serum steroid levels in ApoE2 carriers might pose an increased risk of MCI in the elderly.


Phase control in the synthesis of magnetic iron sulfide nanocrystals from a cubane-type Fe-S cluster.
Phase control has been achieved in the synthesis of magnetic iron sulfide nanocrystals by the use of a single source precursor, a cubane type Fe-S cluster, bis(tetra-n-butylammonium) tetrakis[benezenethiolato-mu3-sulfido-iron]. This cluster cleanly decomposes in alkylamines to yield nanocrystals whose composition, structure, and dimensions are dependent on the temperature employed. At low temperatures, pyrrhotite type Fe7S8 nanocrystals with an average diameter of 5.6 nm are obtained. Higher temperatures yield griegite-Fe3S4 nanocrystals whose dimensions are tunable in the range 2.5-4.5 nm. All the obtained nanocrystals are superparamagnetic at room temperature.


Structures, Electronic Properties, and Interactions of Cetyl Alcohol with Cetomacrogol and Water: Insights from Quantum Chemical Calculations and Experimental Investigations.
The complexes of cetyl alcohol, cetomacrogol-1000, and water were successfully synthesized. The complexes were characterized by freeze-drying scanning electron microscopy, small-angle X-ray diffraction (SAXD), and ultra-SAXD. Furthermore, structures, electronic properties (the HOMO-LUMO gap, ionization potential, electron affinity, electronegativity, hardness, softness, dipole moment, and polarizability), and Raman spectra of cetyl alcohol, cetomacrogol-1000, and their binary and ternary complexes with water were also studied using density functional theory. The calculated lengths of hydrophilic heads in the ternary complexes were in good agreement with SAXD data. The results indicated the existence of two types of interlamellar spacings between successive swollen bilayers (approximately 144 and 72 Å) when polyoxyethylene groups of cetomacrogol-1000 molecules were completely hydrated and stretched. Besides, in comparison with the monomers, the ternary complex of cetyl alcohol, cetomacrogol-1000, and water with the molecular ratio of 1:1:1 (cetyl-ceto-H2O-1 complex) had outstanding properties.


The effectiveness of vitamin C on quinalphos ileal toxicity: a study of histological, ultrastructural, and oxidative stress markers.
There is a significant hazard of human exposure to the organophosphates which is a constant threat, and they are responsible for numerous cases of poisoning and mammalian toxicity annually in non-target wildlife. The antioxidants, including the vitamin C (Vit C), have a protective effect on some organophosphorus compounds-induced organ damage. Quinalphos (QP) is one of these compounds. The investigation's objective is to see if there was any effect of QP on the rat ileum which could be rectified by using Vit C. Three groups of 24 animals were created. As a control, the first group was given pure water. Second group subjected to oral gavages of QPs. Third group rats were given oral gavages of Vit C plus QPs for 10 days. The reaction of ileal enterocytes to food-borne QPs was marked by poorly organized microvilli, numerous vacuoles within them, disrupted nuclei with chromatin margination, disoriented mitochondria, and an expanded intercellular space. The absorptive columnar cell illustrated many vacuoles inside with herniation of microvilli, and normal goblet cells were also seen. Many Paneth cells towards the lumen of intestinal gland contained secretory granules of different sizes and shapes. The histological architecture of the ileal mucosa in the QP plus Vit C group was found to be close to those of healthy controls. The outcomes of this study suggest that administering Vit C in rats treated with QPs protects them from ill dysfunction caused by QP.


A Comparative Assessment of the Inflammatory Markers in Patients with Fibromyalgia under Duloxetine Treatment.
This study was carried out to compare the levels of inflammatory markers in the complete blood count before and after they began receiving duloxetine in patients with fibromyalgia syndrome (FMS). The patient and control groups were composed of 40 patients diagnosed with FMS in accordance with the 2016 American College of Rheumatology (ACR) criteria and 40 healthy volunteers, respectively. The data collection tools comprised the sociodemographic information form, the fibromyalgia impact questionnaire (FIQ), and the sleep hygiene index (SHI), which were used to assess patients' sociodemographic characteristics, FMS disease activity, and sleep quality, respectively. The inflammatory markers of the patient group were assessed by complete blood count before and after the duloxetine treatment and compared with those of the control group. The white blood cell (WBC), neutrophil, and lymphocyte counts were significantly higher in the patient group than in the control group (p < 0.001, p = 0.036 and p = 0.004, respectively). Moreover, platelet distribution width (PDW) was significantly lower, whereas mean platelet volume (MPV) was significantly higher in the patient group than in the control group (p < 0.001 for both cases). In addition to patients' platelet-to-lymphocyte ratio (PLR) values, C-reactive protein (CRP) levels, and white blood cell (WBC) counts decreasing but not significantly (p = 0.083, p = 0.068, and p = 0.065, respectively), their neutrophil-to-lymphocyte ratio (NLR), hemoglobin (Hgb), and hematocrit (Hct) values declined substantially after commencing duloxetine treatment (p = 0.001, p = 0.008, and p = 0.001, respectively). The significant reduction in NLR, Hgb, and Hct levels following duloxetine treatment may indicate that these parameters can be utilized as biomarkers in determining the efficacy of treatment and in the follow-up of the treatment in FMS patients.


Identification and Classification of Human Body Exercises on Smart Textile Bands by Combining Decision Tree and Convolutional Neural Networks.
In recent years, human activity recognition (HAR) has gained significant interest from researchers in the sports and fitness industries. In this study, the authors have proposed a cascaded method including two classifying stages to classify fitness exercises, utilizing a decision tree as the first stage and a one-dimension convolutional neural network as the second stage. The data acquisition was carried out by five participants performing exercises while wearing an inertial measurement unit sensor attached to a wristband on their wrists. However, only data acquired along the z-axis of the IMU accelerator was used as input to train and test the proposed model, to simplify the model and optimize the training time while still achieving good performance. To examine the efficiency of the proposed method, the authors compared the performance of the cascaded model and the conventional 1D-CNN model. The obtained results showed an overall improvement in the accuracy of exercise classification by the proposed model, which was approximately 92%, compared to 82.4% for the 1D-CNN model. In addition, the authors suggested and evaluated two methods to optimize the clustering outcome of the first stage in the cascaded model. This research demonstrates that the proposed model, with advantages in terms of training time and computational cost, is able to classify fitness workouts with high performance. Therefore, with further development, it can be applied in various real-time HAR applications.


Radiation and subsequent reirradiation outcomes in the treatment of diffuse intrinsic pontine glioma and a systematic review of the reirradiation literature.
Diffuse intrinsic pontine glioma (DIPG) is a devastating pediatric disease, with a median survival of <1 year. Here, we review our institution's DIPG experience over an 8-year interval and perform a systematic review of the literature, specifically evaluating reports of reirradiation (reRT) for DIPG. We retrospectively reviewed the medical records of 26 patients who underwent definitive intensity modulated radiation therapy (IMRT) for DIPG at a single institution between 2007 and 2015. Three of these patients underwent reRT for progressive disease. Clinical endpoints, including progression-free survival and overall survival (OS), were assessed. We then performed a thorough PubMed search of the literature discussing reRT for patients with DIPG. Twenty-four of the 26 patients (92%) completed the initial course of radiation (54 Gy in 1.8-Gy fractions using IMRT). Median age at diagnosis was 6.0 years (range, 2.0-26.5). With respect to systemic therapy, 1 (4.2%) received no systemic therapy, 1 (4.2%) received concurrent systemic therapy alone, 4 (16.7%) received adjuvant therapy alone, and 18 (75%) received a combination of concurrent and adjuvant therapy. Median follow-up time was 11 months from the date of initial diagnosis. Median OS for the cohort was 12 months, with a 1-year OS of 51%. The 3 patients who underwent reRT received 20 Gy in 10 daily fractions using IMRT alone with no treatment toxicity noted. Radiation therapy is essential in the definitive management of DIPG. With advances in treatment techniques, it is feasible to reirradiate select patients with progressive disease; however, further research is warranted to optimize dose, delivery, and patient selection in the recurrent/progressive setting. In the future, it may be reasonable to propose more focal delivery of reRT (ie, hypofractionated radiation) in select patients with the goal of reducing treatment time and providing effective palliation.


Social networks and the mental health among Chinese older adults: the mediating role of loneliness and moderating role of Internet use.
Although a large body of research suggests that social networks from family and friends are important factors in protecting the mental health of older adults, we know little about the mediating and moderating mechanisms behind this relationship. Using China as an example, this study aims to investigate a comprehensive model that includes social networks, loneliness, Internet use, and mental health outcomes in the older population. We analyzed data from 7,648 Chinese older people over 60 using the 2018 CLASS survey. We studied how various social networks affect their mental health. Using SPSS's PROCESS macro, we first employed descriptive statistics to examine the characteristics of the participants and calculate the correlations of core variables. Then, we assessed whether loneliness mediated this relationship and tested the moderated mediation effect of Internet use. Our findings shed light on these complex dynamics. The statistics indicate a positive correlation between social networks and mental health. Furthermore, mediation models revealed that loneliness moderates the relationship between social networks and mental health. In addition, moderated mediation models revealed that Internet use played a distinct function in the family networks model compared to the friend networks model. Internet use moderates explicitly the effects of family networks on loneliness and friend networks on mental health. The findings emphasize the importance of differentiating the types of social networks to understand their impact on older adults well-being, encouraging policymakers, medical professionals, and families to adopt more targeted approaches when devising policy interventions and medical strategies, especially for older individuals with insufficient social support. Additionally, we urge governments to recognize the varying types of social networks among older populations and harness the protective effects of Internet technology on their well-being within a digital society.


Separation of Mycobacterium smegmatis From a Mixed Culture Using the Cell Wall Binding Domain of D29 Mycobacteriophage Endolysin.
Pathological infection caused by Mycobacterium tuberculosis is still a major global health concern. Traditional diagnostic methods are time-consuming, less sensitive, and lack high specificity. Due to an increase in the pathogenic graph of mycobacterial infections especially in developing countries, there is an urgent requirement for a rapid, low cost, and highly sensitive diagnostic method. D29 mycobacteriophage, which is capable of infecting and killing M. tuberculosis, projects itself as a potential candidate for the development of novel diagnostic methods and phage therapy of mycobacterial infections. In our previous study, we showed that the cell wall binding domain [C-terminal domain (CTD)] located at the C-terminal end of the D29 mycobacteriophage LysA endolysin very selectively binds to the peptidoglycan (PG) of Mycobacterium smegmatis and M. tuberculosis. Here, by using M. smegmatis as model organism and by exploiting the PG binding ability of CTD, we have developed a method to isolate M. smegmatis cells from a mixed culture via magnetic separation. We show that green fluorescent protein (GFP)-tagged CTD (CTD-GFP) can bind to M. smegmatis cells in vitro after treatment with non-ionic detergent Triton X-100. Fluorescence-based assays show that CTD-GFP binding to M. smegmatis cells is highly specific and stable, and is not disrupted by an excess of either GFP or BSA. We further fused CTD with glutathione-S-transferase (GST) to generate CTD-GST protein and carried out an anti-GST antibody-mediated coating of CTD-GST on Dynabeads. This allowed us to perform successful magnetic separation of M. smegmatis from a mixed culture of bacteria having both Gram-negative and Gram-positive bacteria. Furthermore, the separated cells could be confirmed by a simple PCR. Thus our assay allows us to separate and identify M. smegmatis from a mixed culture.


Mutated alleles of the rod and cone Na-Ca+K-exchanger genes in patients with retinal diseases.
To study the possible involvement of the rod (SLC24A1) and cone (SLC24A2) Na-Ca+K exchanger (NCKX) genes in retinal diseases. DNA was collected from unrelated patients with retinal disease, mainly from North America. A human genomic library was screened with the cone NCKX cDNA, and hybridizing clones were sequenced to determine the genomic organization of the SLC24A2 gene. The single-strand conformation polymorphism (SSCP) technique and direct sequencing were used to screen the patients' DNA for mutations in SLC24A1 and SLC24A2. The effect of selected missense changes on protein function was tested by measuring potassium-dependent Na-Ca exchange of the mutant proteins expressed in insect cells. Twenty-seven novel sequence changes were found in the rod NCKX gene, 21 of which are unlikely to be pathogenic, because they did not cosegregate with the disease or did not affect conserved regions of the protein. Of the remaining six, two were frameshift mutations found in one patient each. If translated, these alleles would encode nonfunctional proteins. Three of the six possibly pathogenic mutations were missense changes located in conserved regions, and their protein functions were assayed. Only one (Ile992Thr) had a significantly low level of exchanger function, but it was found in two unrelated patients who were heterozygotes with different retinal diseases, and this mutation could not be unequivocally associated with either disease. The last of the six changes is likely to create a new splice acceptor site. The genomic organization of the cone NCKX gene was determined, and it contained 11 exons with a few splice variants. Fifteen novel sequence changes were identified in the cone exchanger gene in patients with a cone dysfunction or degeneration. Only three of these sequence changes, all missense changes found in heterozygous patients, were considered possibly pathogenic. Functional analysis showed only a slight reduction in the activity of the corresponding mutant proteins. Although variant alleles of the rod and cone NCKX genes were found, none could be definitively associated with a specific retinal disease. The human phenotype associated with mutant exchanger alleles remains unknown.


Status of the name Argolis in Insecta.
The purpose of the present notice is to identify and clarify a case of mistaken homonymy surrounding the name Argolis, pertaining to Lepidoptera, Hemiptera, and Coleoptera. It is here demonstrated that "Argolis" (Boisduval 1836: 2) is an incorrect original spelling of Ergolis Boisduval, 1836 (Lepidoptera: Nymphalidae); therefore, Argolis Stål, 1861 (Hemiptera: Reduviidae) is the valid senior synonym of Caunus Stål, 1865, while Argolis Chapuis, 1874 (Coleoptera: Chrysomelidae) remains a junior homonym. The following details summarize the situation:.


High-resolution (13)C nuclear magnetic resonance spectroscopy pattern recognition of fish oil capsules.
13C NMR (nuclear magnetic resonance) spectroscopy, in conjunction with multivariate analysis of commercial fish oil-related health food products, have been used to provide discrimination concerning the nature, composition, refinement, and/or adulteration or authentication of the products. Supervised (probabilistic neural networks, PNN) and unsupervised (principal component analysis, PCA; Kohonen neural networks; generative topographic mapping, GTM) pattern recognition techniques were used to visualize and classify samples. Simple PCA score plots demonstrated excellent, but not totally unambiguous, class distinctions, whereas Kohonen and GTM visualization provided better results. Quantitative class predictions with accuracies >95% were achieved with PNN analysis. Trout, salmon, and cod oils were completely and correctly classified. Samples reported to be salmon oils and cod liver oils did not cluster with true salmon and cod liver oil samples, indicating mislabeling or adulteration.


Investigation of sol-gel transition in pluronic F127/D2O solutions using a combination of small-angle neutron scattering and monte carlo simulation.
Physical gelation in the concentrated Pluronic F127/D2O solution has been studied by a combination of small-angle neutron scattering (SANS) and Monte Carlo simulation. A 15% F127/D2O solution exhibits a sol-gel transition at low temperature and a gel-sol transition at the higher temperature, as evidenced by SANS and Monte Carlo simulation studies. Our SANS and simulation results also suggest that the sol-gel transition is dominated by the formation of a percolated polymer network, while the gel-sol transition is determined by the loss of bound solvent. Furthermore, different diffusion behaviors of different bound solvents and free solvent are observed. We expect that this approach can be further extended to study phase behaviors of other systems with similar sol-gel phase diagrams.


Effects of a cholinergic nootropic (WEB 1881 FU) on event-related potentials recorded in incidental and intentional memory tasks.
In a double-blind placebo-controlled randomized study the influence of a cholinergic nootropic (WEB 1881 FU) on event-related brain potentials (ERPs) related to memory performance was investigated. Two different encoding modes were imposed on the subjects, who had to memorize word lists. No significant drug effects were obtained on memory performance and the ERP-concomitant of encoding, the Dm, while ERP effects related to memory were clearly present. However, the two dosages of the drug significantly influenced the overall amplitude of the late cognitive ERP components, suggesting its effect on cognitive processes.


Molecular reorganization of Cx43, Zo-1 and Src complexes during the endocytosis of gap junction plaques in response to a non-genomic carcinogen.
The gap junction protein connexin 43 (Cx43) exhibits dynamic trafficking that is altered in most tumor cells and in response to carcinogen exposure. A number of connexin (Cx)-binding proteins are known to be involved in endocytic internalization of gap junctions. Here, we analyzed the discrete molecular interactions that occur between Src, ZO-1 and Cx43 during Cx43 internalization in response to the non-genomic carcinogen gamma-hexachlorocyclohexane (HCH). Internalization of the Cx43 gap junction plaque was significantly accelerated in Cx43-GFP transfected 42GPA9 Sertoli cells that were exposed to the carcinogen. HCH induced the rapid recruitment of Src to the plasma membrane, activation of Src within 3 minutes and the efficient inhibition of gap junctional coupling, but had no effect in the presence of the Src inhibitor PP2. Immunoprecipitation experiments demonstrated that HCH increased Cx43-Src interaction and concomitantly decreased Cx43-ZO-1 association. ZO-1 was detected on both sides of the gap junction plaques in untreated cells, but appeared to be mainly localized on one side during HCH-induced internalization. The dissociation of ZO-1 from Cx43 appears to occur specifically on the side of the plaque to which Src was recruited. These findings provide mechanistic evidence by which internalization of the Cx43 gap junction plaque might be initiated, suggesting that Src-mediated dissociation of ZO-1 from one side of the plaque initiates endocytic internalization of gap junctions and that this process is amplified in response to exposure to HCH.


Natural Antioxidant Potential of Melon Peels for Fortified Foods.
Agricultural and food waste recycling reduces natural resource losses, contributing significantly to the development of new green markets through the creation of redesigned products. In order to cycle valuable molecules, the peels from Italian cantaloupe (Cucumis melo L.) cultivars were studied and successfully characterized for high-added biomolecules to verify their possible exploitation as wealthy biomasses. Peels were investigated for their cell wall-modifying and browning enzymes, as well as for total polyphenols, ortho-diphenols, flavonoids, tannins, and antioxidant properties. The results of the analyses displayed great promise in one of the three cultivars investigated. Later on, a preliminary study using the best peel extract as a dietary supplement was carried out by preparing fortified seawater to enhance its antioxidant power. The effects of storage time (60 days) were examined at two temperatures through the determination of the stability of the polyphenol content. The kinetic parameters of degradation were also calculated. The "enriched sea water" retained great antioxidant activity in refrigerated conditions, demonstrating that there is good potential for melon by-products to add their natural compounds for food fortification. These findings may provide valuable data for scale-up, from the lab to the pilot or industrial application.


Genetic aspects of anti-neutrophil cytoplasmic antibody-associated vasculitis.
The genetics of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complex area of investigation because of the low frequency of AAVs, the rarity of familial cases and the complexity of disease phenotypes. However, recent studies have been able to gather significant numbers of patients, and multicentre collaborative efforts have allowed the performance of two genome-wide association studies (GWASs). Genetic association studies based on candidate gene approaches and the two GWASs have greatly contributed to our current understanding of the genetic basis of AAV. The central role of autoimmunity has been confirmed by the significant association with HLA polymorphisms; interestingly, the three main AAV subtypes are associated with distinct HLA variants, i.e. granulomatosis with polyangiitis (Wegener's GPA) with HLA-DP1, microscopic polyangiitis with HLA-DQ and eosinophilic GPA (Churg-Strauss) with HLA-DRB4. GWASs also revealed that polymorphic variants of genes encoding proteinase 3 (PR3), the predominant antigenic target of ANCA in GPA, and its main inhibitor, alpha-1 antitrypsin, are highly associated with GPA and, even more significantly, with PR3-ANCA positivity (regardless of the clinical diagnosis); this emphasizes the central pathogenic role of PR3 and humoral autoimmunity in PR3-ANCA positive vasculitis. Finally, candidate gene approach studies have shown associations with other variants involved in autoimmunity, such as those belonging to the CTLA-4 and PTPN22 genes, although these findings warrant replication in larger studies. Additional studies are underway to better characterize disease associations within the AAV spectrum, which could provide new pathogenetic clues and possibly new treatment targets.


Health-care charges generated by patients with diabetes.
For assessment of health-care charges generated by patients with diabetes, 50 patients (25 who were older than 65 years and 25 who were age 65 or younger) whose primary care had been delivered between 1990 and 1995 by a single diabetologist were randomly selected. Institutional health-care bills were accessed from all but three medical center billing offices (dermatology, psychiatry, and radiation oncology areas did not respond). For each dollar billed by endocrinology, the hospital billed 25.90 dollars, other medical specialties 2.70 dollars, surgery 1.10 dollars, radiology 0.70 dollars and pathology 0.60 dollars. The charges generated by the endocrinologist-diabetologist account for approximately 3% of the total charges for the care of the patient with diabetes mellitus in a fee-for-service practice. Although the endocrinologist-diabetologist provides the most cost-effective medical service for patients with diabetes, low reimbursement jeopardizes the practice of this subspecialty.


Occurrence of influenza A(H1N1)v virus in Western Romania in relationship to international travel.
Epidemiological and clinical characteristics of the first cases of infection with the novel influenza A (H1N1) variant virus [A(H1N1)v] admitted to a reference hospital in Western Romanian from mid-June to mid-July 2009 are overviewed. Of 74 suspected cases, 7 were laboratory confirmed. All patients were either Romanian citizens, or people originating from Romania and established overseas. The median age was 13 years and the mean length of hospital stay was 7.7 days. Cough (n = 6) and fever (n = 4) were the most commonly reported symptoms, and all cases made complete recovery. Early diagnosis and management of H1N1 flu was not problematic for the infectious disease specialists. Because many Romanians established overseas come yearly to visit their relatives, special attention must be addressed to the international flight passengers.


Peptide-Mediated Targeting Mesoporous Silica Nanoparticles: A Novel Tool for Fighting Bladder Cancer.
Transitional cell carcinoma of the bladder is particularly devastating due to its high rate of recurrence and difficulty in retention of treatments within the bladder. Current cystoscopic approaches to detect and stage the tumor are limited by the penetrative depth of the cystoscope light source, and intravesical dyes that highlight tumors for surgical resection are non-specific. To address the needs for improved specificity in tumor detection and follow-up, we report on a novel technology relying on the engineered core of mesoporous silica (MSN) with surface modifications that generate contrast in fluorescence and magnetic resonance imaging (MRI). The particle surface was further functionalized to include a bladder cancer cell specific peptide, Cyc6, identified via phage display. This peptide possesses nanomolar specificity for bladder cancer cells and homology across multiple species including mouse, canine, and human. Our study takes advantage of its target expression in bladder tumor which is not expressed in normal bladder wall. When functionalized to MSN, the Cyc6 improved binding efficiency and specificity for bladder cancer cells in vitro. In an in vivo model, MSN instilled into bladders of tumor-bearing mice enhanced T 1- and T 2-weighted MRI signals, improving the detection of the tumor boundaries. These findings support the notion that our targeted nanomaterial presents new options for early detection and eventual therapeutic intervention. Ultimately, the combination of real-time and repeated MRI evaluation of the tumors enhanced by nanoparticle contrast have the potential for translation into human clinical studies for tumor staging, therapeutic monitoring, and drug delivery.


Explaining disparities in HIV infection among black and white men who have sex with men: a meta-analysis of HIV risk behaviors.
To identify factors that contribute to the racial disparity in HIV prevalence between black and white men who have sex with men (MSM) in the United States. A comprehensive literature search of electronic databases, online bibliographies, and publication reference lists yielded 53 quantitative studies of MSM published between 1980 and 2006 that stratified HIV risk behaviors by race. Meta-analyses were performed to compare HIV risks between black and white MSM across studies. Compared with white MSM, black MSM reported less overall substance use [odds ratio (OR), 0.71; 95% confidence interval (CI), 0.53-0.97], fewer sex partners (OR, 0.64; 95% CI, 0.45-0.92), less gay identity (OR, 0.29; 95% CI, 0.17-0.48), and less disclosure of same sex behavior (OR, 0.42; 95% CI, 0.30-0.60). HIV-positive black MSM were less likely than HIV-positive white MSM to report taking antiretroviral medications (OR, 0.43; 95% CI, 0.30-0.61). Sexually transmitted diseases were significantly greater among black MSM than white MSM (OR, 1.64; 95% CI, 1.07-2.53). There were no statistically significant differences by race in reported unprotected anal intercourse, commercial sex work, sex with a known HIV-positive partner, or HIV testing history. Behavioral risk factors for HIV infection do not explain elevated HIV rates among black MSM. Continued emphasis on risk behaviors will have only limited impact on the disproportionate rates of HIV infection among black MSM. Future research should focus on the contribution of other factors, such as social networks, to explain racial disparities in HIV infection rates.


Lymphatic Drainages to the Paravertebral and Pararenal Lymph Nodes in Breast Cancer Patients.
An efficient evaluation of the lymphatic drainage from the breasts (thoracic wall) and/or the upper limbs is essential in the management of patients with breast cancer (BC) and/or BC-related lymphedema. Lymphoscintigraphy was performed in 2 patients with lymphedema. Lymphatic drainage was observed from the upper limb or breast to the posterior paravertebral and/or pararenal lymph nodes. The cases demonstrate lymphatic drainage pathways toward unusual and mostly unrecognized lymph nodes, which may be at risk for further evolution of BC and may be important for the physical treatment of BC-related lymphedema.


Green, Water-Dispersible Photoluminescent On-Off-On Probe for Selective Detection of Fluoride Ions.
Considering the high toxicity and widespread availability of fluoride ions in different environmental matrices, it is imperative to design a probe for its detection. In view of this, a selective fluorescent on-off-on probe based on carbon quantum dots (CQDs) and Eu3+ has been designed. We have synthesized water-soluble carboxylic acid-functionalized CQDs and monitored their interaction with Eu3+. Luminescence quenching in the CQD emission was observed (switch-off) on adding Eu3+ ions. We investigate the reason for this luminescence quenching using time-resolved emission and high-resolution transmission electron microscopy (HRTEM) studies and observed that both electron transfer from CQDs to Eu3+ and aggregation of CQDs are responsible for the luminescence quenching. ζ-Potential and X-ray photoelectron spectroscopy studies confirm Eu3+ binding with the COOH groups on CQD surface. Interestingly, luminescence regains after the addition of fluoride ions to the CQDs/Eu3+ system (switch-on). This has been assigned to the removal of Eu3+ from the CQD surface due to the formation of EuF3 and is confirmed by X-ray diffraction and HRTEM measurements. The sensitivity of the probe was tested by carrying out experiments with other competing ions and was found to be selective for fluoride ions. Experiments with variable concentrations of fluoride ions suggest that the working range of the probe is 1-25 ppm. The probe has been successfully tested for the detection of fluoride ions in a toothpaste sample and the results were compared to those of ion chromatography. To the best of our knowledge, this is the first report based on CQDs and Eu3+ for the detection of fluoride ions, wherein a clear mechanism of the detection has been demonstrated, which, in turn, will help to develop better detection methods. The suggested probe is green, economical, rapid, efficient, and, most importantly, selective and can be used for the detection of fluoride ions in real environmental samples.


[A clinical analysis of patients with early-stage prostate cancer managed without initial treatment].
To search for a more suitable qualification indicating watchful waiting, we performed a retrospective study against early-stage prostate cancer patients managed without initial treatment. Thirty-three patients who had not been treated for more than 6 months after diagnosed as T1c or T2 prostate cancer were studied. The median values of total observation period, age at diagnosis, and initial PSA were 27.0 months, 69.0 years old, and 7.0 ng/ml, respectively. Among 28 patients who had had measurement of serum PSA at least three times, seven patients showed a significant PSA elevation when transition of PSA level was analyzed using linear regression analysis. The other patients had been stable or PSA level declined. Between these two groups, there was no significant difference regarding age, initial PSA, PSA density, Gleason score, number of cancer-positive core, and cancer-occupying rate in biopsy specimen. The median PSA doubling time in patients showing PSA elevation was 36.3 months. There were no patients showing PSA elevation among those with a cancer-occupying rate of less than 5%. Clinical disease progression was obviously observed in two cases although one did not show PSA elevation. During the observation period, treatment was eventually started in seven patients. The 5-year rate of no treatment was 53.8%. Although a significant independent factor predicting the future treatment was not identified, univariate analysis revealed that the initial PSA value in patients undergoing treatment was significantly higher than that of those without treatment (p = 0.032). We concluded that early-stage prostate cancer has clinical variability, and regular clinical evaluations as digital rectal examination should be performed when the patient was managed with watchful waiting.


The influence of outcome desirability on optimism.
People are often presumed to be vulnerable to a desirability bias, namely, a tendency to be overoptimistic about a future outcome as a result of their preferences or desires for that outcome. In this article, this form of wishful thinking is distinguished from the more general concepts of motivated reasoning and overoptimism, and the evidence for this bias is reviewed. The authors argue that despite the prevalence of the idea that desires bias optimism, the empirical evidence regarding this possibility is limited. The potential for desires to depress rather than enhance optimism is discussed, and the authors advocate for greater research attention to mediators of both types of effects. Nine possible mediational accounts are described, and critical issues for future research on the desirability bias are discussed.


Iatrogenic giant coronary artery pseudoaneurysm with "daughter aneurysm" formation: serial imaging findings and natural history.
Coronary pseudoaneurysms rarely occur spontaneously; rather, they are more commonly seen as a complication of coronary intervention. We present a case of a giant right coronary artery pseudoaneurysm with partial thrombosis after arterial perforation during percutaneous intervention for acute myocardial infarction and formation of a "daughter aneurysm" due to a contained rupture 12 years later. Right coronary pseudoaneurysm repair and coronary artery bypass grafting were eventually performed 16 years after the acute event. Cardiac magnetic resonance imaging, coronary computed tomography angiography, and autopsy findings are shown.


Bioinformatic analysis of computational identified differentially expressed genes in tumor stoma of pregnancy‑associated breast cancer.
The present study aimed to screen the differentially expressed genes (DEGs) in tumor‑associated stroma of pregnancy‑associated breast cancer (PABC). By analyzing Affymetrix microarray data (GSE31192) from the Gene Expression Omnibus database, DEGs between tumor asso-ciated stromal cells and normal stromal cells in PABC were identified. Gene Ontology (GO) function and pathway enrichment analyses for the DEGs were then performed, followed by construction of a protein‑protein interaction (PPI) network. A total of 94 upregulated and 386 downregulated DEGs were identified between tumor associated stromal cells and normal stromal cells in patients with PABC. The upregulated DEGs were primarily enriched in the cytokine‑cytokine receptor interaction pathway and GO terms associated with the immune response, which included the DEGs of interleukin 18 (IL18) and cluster of differentiation 274 (CD274). The downregulated DEGs were primarily involved in GO terms associated with cell surface receptor linked signal transduction and pathways of focal adhesion and pathways in cancer. In the PPI network, nodes of jun proto‑oncogene (JUN), FBJ murine osteosarcoma viral oncogene homolog (FOS), V‑myc avian myelocytomatosis viral oncogene homolog (MYC), and alpha‑smooth muscle actin (ACTA2) had higher degrees. The hub genes of JUN, FOS, MYC and ACTA2, as well as the DEGs IL18 and CD274 that were associated with the immune response in GO terms may exert important functions in the molecular mechanisms of PABC. These genes may be used as new molecular targets in the treatment of this disease.