Visible light sensitization of benzoyl azides: cascade cyclization toward oxindoles via a non-nitrene pathway.
Visible light sensitization of benzoyl azides was examined in reaction with N-phenylmethacrylamides to afford biologically important oxindoles and spirooxindoles via a cascade cyclization under mild reaction conditions. Mechanistic studies suggested a non-nitrene pathway, where triplet benzoyl azides act as the reactive intermediate.


Activation of alpha1A-adrenoceptors by genistein at concentrations lower than that to inhibit tyrosine kinase in cultured C2C12 cells.
Genistein, an isoflavonoid natural product, is widely used to inhibit protein tyrosine kinase (PTK). In the present study, we investigated the possible influence of genistein on alpha (1)-adrenoceptors (AR) in cultured C2C12 cells. Genistein enhanced the uptake of radioactive glucose into C2C12 cells in a concentration-dependent manner. Similar results were also observed in samples treated with daidzein, the inactive congener for PTK inhibition. The effect of genistein on alpha (1)-AR was further characterized using the displacement of [ (3)H]prazosin binding in C2C12 cells. The increase in radioactive glucose uptake by genistein was abolished by RS17053 at a concentration sufficient to block alpha (1A)-AR. The pharmacological inhibition of phospholipase C (PLC) by U73122 resulted in a concentration-dependent reduction of genistein-stimulated glucose uptake in C2C12 cells. This inhibition by U73122 was specific because the inactive congener, U73343, failed to modify the action of genistein. Moreover, genistein can activate alpha (1A)-AR at a concentration (1 micromol/L) lower than that (50 micromol/L) needed to abolish the insulin-stimulated phosphorylation of PTK. The obtained data indicate an activation of alpha (1A)-AR by genistein to increase the glucose uptake into C2C12 cells and this supports the application of genistein as a TK inhibitor.


Unfinished Root Canal Treatments and the Risk of Cardiovascular Disease.
Root canal treatments (RCTs) aim to eradicate pulpal diseases and save the infected teeth by eliminating microorganisms from the root canal system. Starting but not finishing an RCT can perpetuate a dead space for bacterial growth, which can spread to other sites in the body and develop systemic symptoms. The objective of the present study was to investigate the association between unfinished RCTs and the risk of cardiovascular disease (CVD) using a nationwide population-based database. A total of 283,590 participants who received at least 1 RCT and with no cardiovascular history before 2005 were recruited and followed until the end of 2011. An unfinished RCT was defined as a tooth on which an RCT was started but with no completion code. Cox proportional hazards models were used to estimate the effect of unfinished RCTs on the risk of CVD. A total of 3626 participants underwent CVD hospitalization during an average observation period of 6.01 years, thus yielding an overall CVD hospitalization incidence rate of 0.21% per person year. Compared with the participants with no unfinished RCTs, the adjusted CVD hospitalization hazard ratio for the participants with 1 or 2 unfinished RCTs was 1.22 (95% confidence interval, 1.11-1.35) and for those with 3 or more unfinished RCTs, it was 3.61 (95% confidence interval, 2.36-5.51; test for trend, P < .0001). Participants with unfinished RCTs were associated with a higher risk of CVD hospitalization.


Gene expression profile of rat adipose tissue at the onset of high-fat-diet obesity.
Morbid obesity is the result of massive expansion of white adipose tissue (WAT) and requires recruitment of adipocyte precursor cells and their supporting infrastructure. To characterize the change in the expression profile of the preexisting WAT at the start of obesity, when adipocyte hypertrophy is present but hyperplasia is still minimal, we employed a cDNA subtraction screen for genes differentially expressed in epididymal fat pads harvested 1 wk after the start of a 60% fat diet. Ninety-six genes were upregulated by at least 50% above the WAT of control rats receiving a 4% fat diet. Of these genes, 30 had not previously been identified. Sixteen of the 96 genes, including leptin, adipocyte complement-related protein 30 kDa, and resistin, were predicted to encode a signal peptide. Ten of the 16 had been previously identified in other tissues and implicated in cell growth, proliferation, differentiation, cell cycle control, and angiogenesis. One was a novel gene. Twenty-nine novel fragments were identified. Thus, at the onset of high-fat-diet-induced obesity in rats, adipose tissue increases its expression of factors previously implicated in the expansion of nonadipocyte tissues and of several uncharacterized novel factors. The only one of these thus far characterized functionally was found to promote lipogenesis.


Effects of sodium acetate as a pH control amendment on the composting of food waste.
A low level of microbial activity due to the production of organic acids is a recognized problem during the initial phase of food waste composting. Increasing such activity levels by adjusting the pH values during the initial composting phase was the primary concern to be investigated. In this study, sodium acetate (NaAc) was introduced as an amendment to an in-vessel composting system. NaAc was added when the pH of the compost mixture reached a low level (pH<5), and its effects on microbial activity, ammonia loss, and organic acid production were then evaluated. The addition of NaAc would lead to an increased pH level within the range from 5.2 to 5.5. This had a positive effect on the degradation of organic materials and the effect was statistically significant compared to the result of control treatment without NaAc addition (p<0.05). Microbial activity in the composting reactor treated with NaAc was also higher than that of the control one after the indigenous microorganisms adapted to the new conditions. However, the microbial populations of these two reactors were not significantly different. Although, ammonia loss was enhanced with the addition of NaAc, with 10.8 and 8.6g in NaAc amendment reactor and control one, respectively, the degree of enhancement was relatively small compared to the total amount of nitrogen in the raw materials (84g). The study results indicated that the NaAc was an effective amendment for inhibiting the production of propionic and butyric acids, and hence counteracting the adverse effects of organic acids to the composting process.


Dual actions of lanthanides on ACTH-inhibited leak K(+) channels.
Bovine adrenal zona fasciculata cells express background K(+) channels (I(AC) channels) whose activity is potently inhibited by ACTH. In whole cell patch clamp recordings, it was discovered that the trivalent lanthanides (Ln(3+)s) lanthanum and ytterbium interact with two binding sites to modulate K(+) flow through these channels. Despite large differences in ionic radii, these Ln(3+)s inhibited I(AC) channels half-maximally with IC(50) values near 50 microM. In addition, these Ln(3+)s blocked and reversed ACTH-mediated inhibition of I(AC) K(+) channels at similar concentrations. The Ln(3+)s did not alter inhibition of I(AC) by angiotensin II or cAMP. Ln(3+)-induced uncoupling of ACTH receptor activation from I(AC) inhibition was prevented by raising the external Ca(2+) concentration from 2 to 10 mM. The divalent cation Ni(2+) (500 microM) also blocked ACTH-dependent inhibition of I(AC) through a Ca(2+)-sensitive mechanism. The results are consistent with a model in which Ln(3+)s produce opposing actions on I(AC) K(+) currents through two separate binding sites. In addition to directly inhibiting I(AC), Ln(3+)s (and Ni(2+)) bind with high affinity to a Ca(2+)-selective site associated with the ACTH receptor. By displacing Ca(2+) from this site, Ln(3+)s prevent ACTH from binding and accelerate its dissociation. These results identify Ln(3+)s as a relatively potent group of noncompetitive ACTH receptor antagonists. Allosteric actions of trivalent and divalent metal cations on hormone binding, mediated through Ca(2+)-specific sites, may be common to a variety of peptide hormone receptors.


Design and Rationale of the Metastatic Renal Cell Carcinoma (MaRCC) Registry: A Prospective Academic and Community-Based Study of Patients With Metastatic Renal Cell Cancer.
The Metastatic Renal Cell Cancer Registry, a large, nationally representative, prospective registry of patients with metastatic renal cell carcinoma (mRCC), aims to understand real-world treatment patterns and outcomes of patients with mRCC in routine clinical practice across the United States. This observational study is designed to enroll 500 patients with previously untreated mRCC from approximately 60 academic and community treatment sites; as of December 7, 2016, 500 patients have enrolled at 54 sites. Key endpoints include real-world data on reasons for treatment initiation and discontinuation; treatment regimens; disease progression; patient-reported outcomes; and healthcare resource utilization in this patient population.


Fascin in lamellipodia contributes to cell elasticity by controlling the orientation of filamentous actin.
Fascin, an actin-bundling protein, is present in the filopodia and lamellipodia of growth cones. However, few studies have examined lamellipodial fascin because it is difficult to observe. In this study, we evaluated lamellipodial fascin. We visualized the actin meshwork of lamellipodia in live growth cones by super-resolution microscopy. Fascin was colocalized with the actin meshwork in lamellipodia. Ser39 of fascin is a well-known phosphorylation site that controls the binding of fascin to actin filaments. Fluorescence recovery after photobleaching experiments with confocal microscopy showed that binding of fascin was controlled by phosphorylation of Ser39 in lamellipodia. Moreover, TPA, an agonist of protein kinase C, induced phosphorylation of fascin and dissociation from actin filaments in lamellipodia. Time series images showed that dissociation of fascin from the actin meshwork was induced by TPA. As fascin dissociated from actin filaments, the orientation of the actin filaments became parallel to the leading edge. The angle of actin filaments against the leading edge was changed from 73° to 15°. This decreased the elasticity of the lamellipodia by 40%, as measured by atomic force microscopy. These data suggest that actin bundles made by fascin contribute to elasticity of the growth cone.


The Comparison of Antioxidant Effect of Aspirin, Metformin, Atorvastatin and Captopril Co-administration in the Heart and Kidney Tissues of Diabetic Rats.
The present study investigated the effects of co-administration of aspirin, metformin, atorvastatin and captopril on serum lipid profile and oxidative stress in the heart and kidney of streptozotocin-induced diabetic rats. In this study, rats were randomly divided into the following eleven groups: control (Cont.), and diabetic (D), as well as 9 groups that were treated with metformin (M, 300 mg/kg) or aspirin (ASA, 120 mg/kg) alone or in different combinations with captopril (C, 50 mg/kg), or atorvastatin (AT, 40 mg/kg), as follows: (D + M), (D + ASA), (D + M + ASA), (D + M + C), (D + M + AT), (D + M + C + ASA), (D + M + C + AT), (D + M + AT + ASA), and (D + M + C + AT + ASA). The rats in treatment groups daily received drugs by gavage for six weeks. Finally, serum lipid profile and levels of oxidative markers in the heart and kidney tissues were evaluated. In diabetic rats, blood levels of glucose, cholesterol, TG (triglyceride), LDL (low-density lipoprotein), MDA (malondialdehyde) and AIP (atherogenic index of plasma) significantly increased but those of HDL (high-density lipoprotein) and total thiol as well as SOD (superoxide dismutase) and CAT (catalase) activities significantly decreased. Treatment with different combinations of C, ASA, AT and M significantly ameliorated these parameters. This study showed that co-administration of ASA, M, C and AT, could improve glucose and lipid metabolism and oxidative stress markers in the kidneys and heart tissues of diabetic rats more markedly than the administration of these drugs alone.


The Effectiveness of Policy Interventions for School Bullying: A Systematic Review.
Bullying threatens the mental and educational well-being of students. Although anti-bullying policies are prevalent, little is known about their effectiveness. This systematic review evaluates the methodological characteristics and summarizes substantive findings of studies examining the effectiveness of school bullying policies. Searches of 11 bibliographic databases yielded 489 studies completed since January 1, 1995. Following duplicate removal and double-independent screening based on a priori inclusion criteria, 21 studies were included for review. Substantially more educators perceive anti-bullying policies to be effective rather than ineffective. Whereas several studies show that the presence or quality of policies is associated with lower rates of bullying among students, other studies found no such associations between policy presence or quality and reductions in bullying. Consistent across studies, this review found that schools with anti-bullying policies that enumerated protections based on sexual orientation and gender identity were associated with better protection of lesbian, gay, bisexual, transgender, and queer (LGBTQ) students. Specifically, LGBTQ students in schools with such policies reported less harassment and more frequent and effective intervention by school personnel. Findings are mixed regarding the relationship between having an anti-bullying policy and educators' responsiveness to general bullying. Anti-bullying policies might be effective at reducing bullying if their content is based on evidence and sound theory and if they are implemented with a high level of fidelity. More research is needed to improve on limitations among extant studies.


Subarachnoid hemorrhage induces dynamic changes in regional cerebral metabolism in rats.
Following a subarachnoid hemorrhage (SAH), adult rats exhibit dynamic regional changes in cerebral glucose metabolism characterized by an increase in metabolic rates and a subsequent upregulation of cytochrome oxidase (CO). We evaluated both local cerebral metabolic rates for glucose (ICMRglc: (mol/100 g/min) and CO in 23 brain regions of interest (ROI). Sham animals underwent anesthesia and superficial surgery; saline-controls received an injection of 0.9% saline into the cisterna magna; and SAH rats received an injection of autologous blood into the cisterna magna. This blood, measured by albumin labeled with radioactive carbon 14, distributed throughout the brain but predominated ventrally. After experimental animals were sacrificed at day 0 (3 h), 1, 3, and 7 days postinjection, ROI were analyzed using [14C]2-deoxy-D-glucose autoradiography and CO histochemistry. ICMRglc in SAH rats increased in many regions (ranging from 0.7% to 32.2% above sham levels). Cytochrome oxidase also increased from 1% to 9% above sham levels, peaking on day 3. Conversely, saline-controls exhibited prolonged depression of ICMRglc (ranging from 11% to 35% below sham levels) and CO (ranging from 4% to 11% below sham levels) from day 0 through day 7. All saline-control ROI for all time points showed this metabolic depression, and between 91% and 95% of saline-control ROI presented lower CO levels as compared to sham. Overall, ICMRglc and CO levels were greater in SAH than in saline-control ROI. However, when considering the influence of subarachnoid blood on metabolic changes in SAH animals, both CO and 2DG levels did not correlate well with the amount of 14C-albumin binding. While previous studies have measured both metabolic rates of glucose and CO soon after SAH, this is the first to simultaneously conduct these measurements in the same SAH rat model.


Alpha 2-adrenoceptor activation inhibits noradrenaline release in human and rabbit isolated renal arteries.
The aim of the present study was to investigate alpha 2-adrenoceptor modulation of noradrenaline release in superfused strips of human and rabbit renal arteries. The arteries were field-stimulated after incubation with [3H]noradrenaline. The stimulation-induced outflow of radioactivity was taken as an index of noradrenaline release. At a high stimulation frequency (4 Hz), the alpha 2-adrenoceptor agonist clonidine (0.1 mumol/l) failed to inhibit stimulation-induced outflow of radioactivity in human and rabbit renal arteries whereas the alpha 2-adrenoceptor agonist UK 14304 (0.1 mumol/l) did inhibit stimulation-induced outflow. The inhibitory effect of UK 14304 in human renal arteries was blocked by the alpha 2-adrenoceptor blocking drug rauwolscine (1 mumol/l). At a lower stimulation frequency (2 Hz), both clonidine and UK 14304 inhibited stimulation-induced outflow of radioactivity from rabbit renal arteries; both effects were blocked by rauwolscine. Rauwolscine by itself enhanced stimulation-induced outflow of radioactivity in both preparations. The results suggest that activation of prejunctional alpha 2-adrenoceptors in human and rabbit renal arteries inhibits noradrenaline release. Neuronally released noradrenaline exerts inhibitory feed-back modulation of its own release through activation of prejunctional alpha 2-adrenoceptors. At a higher stimulation frequency most of the prejunctional alpha 2-adrenoceptors are already occupied by endogenous noradrenaline and clonidine fails to inhibit noradrenaline release since it seems to act as a partial agonist at these prejunctional alpha 2-adrenoceptors.


Incentive Processing in Persistent Disruptive Behavior and Psychopathic Traits: A Functional Magnetic Resonance Imaging Study in Adolescents.
Children with early-onset disruptive behavior disorder (DBD), especially those with callous-unemotional traits, are at risk of developing persistent and severe adult antisocial behavior. One possible underlying mechanism for persistence is deficient reward and loss sensitivity, i.e., deficient incentive processing. However, little is known about the relation between deficient incentive processing and persistence of antisocial behavior into adulthood or its relation with callous-unemotional and other psychopathic traits. In this study, we investigate the relationship between the neural correlates of incentive processing and both DBD persistence and psychopathic traits. In a sample of 128 adolescents (mean age 17.7) with a history of criminal offending before age 12, functional magnetic resonance imaging was performed during a monetary incentive delay task designed to assess neural responses during incentive processing. Neural activation during incentive processing was then associated with DBD persistence and psychopathic traits, measured with the Youth Psychopathic Traits Inventory. Compared with both healthy control subjects and youths who had desisted from DBD, persistent DBD subjects showed lower neural responses in the ventral striatum during reward outcomes and higher neural responses in the amygdala during loss outcomes. Callous-unemotional traits were related to lower neural responses in the amygdala during reward outcomes, while other psychopathic traits were not related to incentive processing. In the current study, aberrant incentive processing is related to persistence of childhood antisocial behavior into late adolescence and to callous-unemotional traits. This mechanism may underlie treatment resistance in a subgroup of antisocial youth and provide a target for intervention.


Phage display technology for fabricating a recombinant monoclonal ScFv antibody against tetanus toxin.
Tetanus is a specific infectious disease, often associated with lower immunization in developing countries and catastrophic events (such as earthquakes). Millions of people, especially children, die every year from tetanus disease. Therefore, it is necessary to devise a rapid and sensitive detection method for tetanus toxin to ensure an early diagnosis and clinical treatment of tetanus. The current study looks at developing a novel, high specific, low-cost, and sensitive ScFv antibody. It is capable of tetanus detection immunoassays in clinical diagnosis, suspicious foods, and water monitoring. For this regard, a high-quality phage display antibody library (8.7 × 107 PFU/ml) was constructed. Tetanus-specific antibodies with high affinity retrieved from libraries. After phage rescue and four rounds of biopanning, clone screening was performed by phage ELISA. Recombinant antibodies expressed from the AC8 clone showed the highest affinity for tetanus. SDS-PAGE and western blotting confirmed the presence of a high-quality, pure ScFv band at 32 kDa. ELISA was used to determine the affinity value, estimated to be around 10-8 M. The results suggest that the proposed detection method by ScFv antibodies is an alternative diagnostic tool enabling rapid and specific detection of the tetanus toxin.


Comparison of Diagnostic Accuracies of Serum HE-4 Levels and 3D Power Doppler Angiography Parameters between Benign Endometrial Pathologies and Endometrial Cancer.
To study the diagnostic accuracies of serum human epididymis protein 4 (HE-4) levels, virtual organ computer-aided analysis (VOCAL) parameters and endometrial volume in endometrial cancer cases. One hundred and seven patients (37 with endometrial cancer and 70 with benign endometrial pathology) were included in this study. VOCAL parameters and serum HE-4 levels were compared between the groups. Area under the curve (AUC) values were 0.702, 0.658, 0.706 for vascularization index (VI), the flow index (FI) and the vascularization flow index (VFI), respectively. A cut off value of 0.568 for VI demonstrated 70% sensitivity, 72% specificity, 56% positive predictive value (PPV) and a81% negative predictive value (NPV). A cut off value of 25.8 for showed a senitivith of 70% and a specificity of 58% with aPPV of 46% and NPV of 78%, and with a cut off value of 0.12 for VFI 70%, 69%, 54% and 81%, respectively. The area under the curve for HE-4 was 0.814. A cut off value of 458 pmol/L was predictive of malignancy with 86% sensitivity and 63% specificity. VOCAL parameters and serum HE-4 levels were statistically significantly higher in the endometrial cancer patients. Serum HE-4 levels provided a greater sensitivity compared to power doppler angiography for predicting malignancy or benign endometrial pathology.


Screening for depressive symptoms.
Several of my female patients of reproductive age seem to be depressed. Is there a simple tool I can use to screen them? Motherisk is using the Edinburgh Postnatal Depression Scale to screen for depression. This simple questionnaire is filled out by women while in the waiting room. Using this tool has helped us identify large numbers of women who are at risk of, but have not been diagnosed with, depression. We believe family physicians should use this screening tool extensively with women of reproductive age.


A descriptive study of the centralization phenomenon. A prospective analysis.
Occurrence and treatment responses associated with the centralization phenomenon were analyzed prospectively in 289 patients with acute neck and back pain with or without referred spinal symptoms. To document symptom changes to mechanical assessment during initial evaluation and during consecutive visits. Using standard operational definitions, patients were categorized reliably into three inclusive and mutually exclusive pain pattern groups: centralization, noncentralization, and partial reduction. It was hypothesized that the occurrence of centralization would be less than previously reported and that the centralization group would have better treatment results. Centralization has been reported to occur with high frequency during mechanical assessments of patients with acute spinal syndromes. When centralization is observed, a favorable treatment result is expected. Because centralization has not been defined consistently in the literature, the true prevalence and treatment responses associated with centralization have not been confirmed. Consecutive patients with neck or back pain syndromes and referred to outpatient physical therapy services were categorized into three pain pattern groups by experienced therapists trained in the McKenzie system. Changes in distal pain location were scored and documented before and after each visit. Maximal pain intensity over 24 hours, perceived functional status, and number of treatment visits were compared between groups. Patients could be categorized reliably according to movement signs and symptoms. The centralization pain pattern group had significantly fewer visits than the other two groups (P < 0.001). Pain intensity rating and perceived function were different between the centralization and noncentralization groups (P < 0.001). There was no difference in treatment response between the centralization and partial-reduction groups (P = 0.306). Prevalence of patients assigned to the three groups was 30.8% in the centralization group, 23.2% in noncentralization, and 46% in the partial-reduction group. Categorization by changes in pain location to mechanical assessment and treatment allowed identification of patients with improved treatment outcomes and facilitated planning of conservative treatment of patients with acute spinal pain syndromes. If a proximal change in pain location is not observed by the seventh treatment visit, the results of this study support additional medical evaluation for physical or nonphysical factors that could be delaying quick resolution of the acute episode.


ClpAP and ClpXP degrade proteins with tags located in the interior of the primary sequence.
Clp/Hsp100 ATPases comprise a large family of ATP-dependent chaperones, some of which are regulatory components of two-component proteases. Substrate specificity resides in the Clp protein and the current thinking is that Clp proteins recognize motifs located near one or the other end of the substrate. We tested whether or not ClpA and ClpX can recognize tags when they are located in the interior of the primary sequence of the substrate. A protein with an NH2-terminal ClpA recognition tag, plasmid P1 RepA, was fused to the COOH terminus of green fluorescent protein (GFP). GFP is not recognized by ClpA or ClpX and is not degraded by ClpAP or ClpXP. We found that ClpA binds and unfolds the fusion protein and ClpAP degrades the protein. Both the GFP and RepA portions of the fusion protein are degraded. A protein with a COOH-terminal ClpX tag, MuA, was fused to the NH2 terminus of GFP. ClpXP degrades MuA-GFP, however, the rate is 10-fold slower than that of GFP-MuA. The MuA portion but not the GFP portion of MuA-GFP is degraded. Thus, a substrate with an internal ClpA recognition motif can be unfolded by ClpA and degraded by ClpAP. Similarly, although less efficiently, ClpXP degrades a substrate with an internal ClpX recognition motif. We also found that ClpA recognizes the NH2-terminal 15 aa RepA tag, when it is fused to the COOH terminus of GFP. Moreover, ClpA recognizes the RepA tag in either the authentic or inverse orientation.


[Electron microscopy as a method of classification of hematopoietic-system tumors].
83 biopsies of lymph nodes and 35 specimens of blood in different types of haematopoietic system oncological involvement were examined electronoptically with a view to finding distinguishing features such as would prove to be better than other methods used in diagnosing the above tumours. In the granulocytic series these proved to be granules though there was a loss of their formation in most of the poorly diagnosable processes. However, it proved to be relatively easy to make use of tests for phagocytosis in myelomonocytes. In the histiocytic series the defining features (phagocytosis and proteosynthesis) proved to be too general in nature to find any relevant use in oncological diagnosis. On the other hand, the rod-like granules of Langerhans' cells proved to be a reliable guide in diagnosing histiocytosis X similarly as the Weibel-Palade granules did in diagnosing endotheliosis. In the lymphocytic series, B series diagnosis can be facilitated by the presence of spatially arranged interdigitations; in the T series interdigitations are either missing or else are arranged in a single plane only. The erythrocytic series is defined by the presence of ferritin while megakaryocytes are defined by the phenomenon of fissure-like communications.--All those features were merely supplementary in nature and could not be used as an independent diagnostic method particularly in view of the small volume of the processed specimens as these did not always contain representative material or else supplied it in a hardly classifiable mixture.


Induction of corneal lesion and nerve fiber sprouting by neonatal capsaicin application depends on the dose of the drug and survival time after treatment.
The effects of capsaicin on the rat cornea and its NsAchE (non specific acetylcholinesterase)-positive nerve fibers were investigated after long and short survival periods following subcutaneous (s.c) injection of the drug. Sixteen rats were injected once s.c with capsaicin on postnatal day 2 at a dose of 50 mg/kg. Age-matched rats were injected only vehicle, and served as control (n = 16). After 4 (n = 6), 8 (n = 6) and 12 (n = 4) mos., both sides of the corneas were examined under a binocular microscope to look for corneal abnormalities. Immediately after the enucleation, bilateral corneas were excised with a thin scleral margin and their ciliary body and iris were removed in DPBS solution. Then, they were fixed in a 4% paraformaldehyde solution containing 8% sucrose for 1 h at 4 degrees C, and processed for staining by the NsAchE method. For comparison, 15 rats were injected 3 times with capsaicin (total dose: 150 mg/kg) at a dose of 50 mg/kg on days 1, 2 and 3 after birth. Age-matched rats (n = 16) were injected vehicle as controls. Five (n = 4), 17 (n = 4), 45 (n = 3) and 75 (n = 4) days later, their corneas were similarly handled as described above. Corneal lesions and sprouting of the NsAchE-positive subepithelial nerve fibers appeared 4 mos. after the treatment with capsaicin (50 mg/kg). In particular, all the treated corneas (8/8) at 12 mos. showed corneal abnormalities. Contrary to the results from the single injection of capsaicin, corneal changes had already appeared on day 17 after treatment with capsaicin at a high dose (150 mg/kg). These data reinforce the suggestion that yielding of corneal lesions is closely associated with the longer survival time at lower doses and with the short survival time at a high dose of the drug. Further, the relationship between sprouting of corneal nerve fibers and corneal wounds was discussed on the basis of the previous reports.


Venous Thromboembolism in Pediatric Inflammatory Bowel Disease: A Scoping Review.
In addition to gastrointestinal symptoms, pediatric inflammatory bowel disease (pIBD) may present with extra-intestinal manifestations including venous thromboembolism (VTE). Prevention and treatment guidelines for VTE in pediatric patients are needed. In this scoping review, we sought to detail the available data on the prevention and management of VTE in pIBD. Using PRISMA extension for Scoping Reviews (PRISMA-ScR), we identified, screened, graded quality of, and analyzed, literature on VTE in pediatric IBD, published between 1967 and 2023. Data were extracted from 107 studies (including 216 patients). IBD patients with VTE had a median age of 14 years. Children with VTE more frequently had ulcerative colitis (70%, n = 216), developed their VTE within the first year of IBD diagnosis (52%, n = 97), had recent steroid use (62%, n = 50), and had central venous catheters (38%, n = 42). Cerebral venous sinus thrombus was the most common VTE type (34% of all VTE). Testing for thrombophilia conditions was rarely available but 65% (n = 23) of subjects tested had elevated Factor VIII activity. While most patients made a full recovery, 5% (n = 11) died secondary to their VTE. While randomized clinical trials assessing interventions to prevent and treat VTE in pIBD would be ideal, the feasibility of doing such studies is low. However, there has been an increase in interest in this topic and an increase in literature over the past decade. As such, a consensus statement from a multidisciplinary group of experts based on available literature and clinical experience would be valuable for practicing clinicians.


Novel Brønsted acidic ionic liquids and their use as dual solvent-catalysts.
The reaction of triphenylphosphine or N-butylimidazole with cyclic sultones gives zwitterions that are subsequently converted into ionic liquids by reaction with trifluoromethane sulfonic acid or p-toluenesulfonic acid. The resulting ionic liquids have cations to which are tethered alkane sulfonic acid groups. These Brønsted acidic ionic liquids are useful solvent/catalysts for several organic reactions, including Fischer esterification, alcohol dehydrodimerization and the pinacol rearrangement. The new ionic liquids combine the low volatility and ease of separation from product normally associated with solid acid catalysts, with the higher activity and yields normally found using conventional liquid acids.


Toxorhynchites-fluorescent antibody system for the detection of bluetongue virus from Culicoides midges (Diptera: Ceratopogonidae).
A new system, the Toxorhynchites-fluorescent antibody (TFA) test in which the larvae of Toxorhynchites splendens mosquitoes were used for the detection of bluetongue virus (BTV) from Culicoides midges, was developed. Twenty-seven pools of Culicoides midges were collected from bluetongue-prone areas of Tamil Nadu by use of the light-trap and suction-trap methods. A suspension of each pool was injected intrathoracically into T. splendens IV instar larvae and inoculated onto Vero cell monolayers. An indirect fluorescent antibody technique and an immunoperoxidase test were used to detect BTV antigen in smears of crushed midges, crushed larval head smears after incubation for 7 d at 28 degrees and cell monolayers showing cytopathic effects 48 h post inoculation. The suspensions were also injected intravenously into embryonated chicken eggs, and the characteristic BTV-induced lesion(s), viz. cherry-red appearance of embryos, were observed after 48 h. Virus was confirmed by a qualitative neutralization test conducted simultaneously in embryonated chicken eggs. A total of seven out of 27 samples (26%) were positive for the presence of BTV antigen in all the diagnostic systems used. Since BTV propagates readily in experimentally infected T. splendens larvae and the BTV antigen can be detected by the fluorescent antibody technique with a sensitivity comparable to that for virus propagated in tissue culture and embryonated eggs, the TFA system can be adopted as a new method for the isolation of BTV from vectors. The advantages of the TFA system are discussed.


Increasing quinolone resistance in Salmonella enterica serotype Enteritidis.
Until recently, Salmonella enterica serotype Enteritidis has remained sensitive to most antibiotics. However, national surveillance data from Denmark show that quinolone resistance in S. Enteritidis has increased from 0.8% in 1995 to 8.5% in 2000. These data support concerns that the current use of quinolone in food animals leads to increasing resistance in S. Enteritidis and that action should be taken to limit such use.


Melanoblast-tissue interactions and the development of pigment pattern in Xenopus larvae.
The melanophores of larval Xenopus laevis are disparately distributed on the hypomere in that the upper region (UHT) is densely pigmented, the median region (MHT) is moderately pigmented, and the lower region (LHT) is unpigmented. The roles of the melanoblasts and their tissue environment in determining the melanophore pattern was investigated by heterotopic transplantation of hypomeric tissues, culture of neural crest explants in vesicles derived from hypomeric tissues and radioactive marking of neural crest cells. Somite-situated grafts of UHT, MHT and LHT were found to possess melanophore densities similar to those exhibited by such hypomeric tissues when in their normal situation. The number and distribution of trunk melanophores in 'crestless' second host larvae bearing grafts of UHT, MHT and LHT transferred from the somites of primary host embryos indicated that (a) many melanoblasts entered all transplants during neural crest migration in the primary host: subsequently, a small number of melanoblasts were lost from transplants of UHT, a greater number from transplants of MHT and almost all from transplants of LHT; (b) almost all melanoblasts migrated out from transplants of MHT and LHT and entered the tissues of the 'crestless' host, whereas a considerable number of melanoblasts remained in the transplant when it was formed from UHT. Grafts of UHT placed mid-ventrally in the hypomere failed to exhibit melanophores. Vesicles of (a) UHT + MHT and (b) LHT containing neural crest tissue possessed similar numbers of melanophores. Vesicles of LHT differed from those of UHT + MHT in that melanophores were densely aggregated in the implanted neural tissues. Following radioactive marking of neural crest cells labelled nuclei were found on the dorsal ridges of the somites, the surfaces of the neural tube and notochord and in the mesoderm of the upper hypomere and the fin, but were absent from the lateral surfaces of the somites. These results showed that the melanophore pattern in larval Xenopus depended upon melanoblast-tissue interactions, which influenced the migration, rather than the differentiation, proliferation or destruction, of melanoblasts and suggested that tissue selection by migrating melanoblasts enabled these cells to distribute themselves in embryonic tissues in accordance with a hierarchy of melanoblast-tissue affinities. Melanoblast-tissue affinities appeared to be related to the adhesiveness of mesodermal cells: melanoblast extensibility appeared to facilitate exploration of the surrounding tissues. The formation of pigment pattern in larval Xenopus appeared to depend upon the interaction between the melanoblast population pressure and melanoblast-tissue affinities. The present results and those of other workers on amphibian pigmentation were used to construct a model capable of accounting for species-specific differences in larval amphibian pigment patterns, in terms of interactions between species-specific differences in melanoblast-tissue affinities and melanoblast population pressure.


Heterogeneity among diffuse large B-cell lymphoma: new entities in WHO classification, a first step in personalized therapy.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma, being part of mature B-cell neoplasm according to the 2016 World Health Organization (WHO) Classification of lymphoid tumors. This type of non-Hodgkin's lymphoma (NHL) can develop in the lymph nodes in most cases, or in extranodal sites (the most frequent involvement being the digestive tract, but also the thyroid, central nervous system, testes, etc.). Despite being an aggressive lymphoma, DLBCL benefits of potentially curable therapy. The addition of monoclonal antibodies to standard chemotherapy in the therapeutic approach of DLBCL leads to some net superior results to those obtained by chemotherapy alone. Despite the fact that the aggressive therapy is very efficient, 10% of patients remain refractory to it, 30-40% of them after obtaining a complete response (CR) will relapse, and 90% of refractory DLBCL have poor survival rates. Based on these findings, an explanation for the differences in clinical outcome and therapy response was attempted. The important progresses made in the understanding of DLBCL heterogeneity were based on molecular biology studies and showed differences in chromosomal alterations and in signaling pathways activation. These findings have paved the way for new therapeutic targets in order to improve therapy response. The large heterogeneity of DLBCL is acknowledged by the 2016 WHO Classification of lymphoid neoplasms, with 17 DLBCL subtypes, some of them as new varieties, compared to the 2008 Classification, and others introduced as provisional entities.


B-1 cells modulate the murine macrophage response to Leishmania major infection.
To investigate the modulatory effect of B-1 cells on murine peritoneal macrophages infected with Leishmania major (L. major) in vitro. Peritoneal macrophages obtained from BALB/c and BALB/c XID mice were infected with L. major and cultured in the presence or absence of B-1 cells obtained from wild-type BALB/c mice. Intracellular amastigotes were counted, and interleukin-10 (IL-10) production was quantified in the cellular supernatants using an enzyme-linked immunosorbent assay. The levels of the lipid mediator prostaglandin E2 (PGE2) were determined using a PGE2 enzyme immunoassay kit (Cayman Chemical, Ann Arbor, MI), and the number of lipid bodies was quantified in the cytoplasm of infected macrophages in the presence and absence of B-1 cells. Culturing the cells with selective PGE2-neutralizing drugs inhibited PGE2 production and confirmed the role of this lipid mediator in IL-10 production. In contrast, we demonstrated that B-1 cells derived from IL-10 KO mice did not favor the intracellular growth of L. major. We report that B-1 cells promote the growth of L. major amastigotes inside peritoneal murine macrophages. We demonstrated that the modulatory effect was independent of physical contact between the cells, suggesting that soluble factor(s) were released into the cultures. We demonstrated in our co-culture system that B-1 cells trigger IL-10 production by L. major-infected macrophages. Furthermore, the increased secretion of IL-10 was attributed to the presence of the lipid mediator PGE2 in supernatants of L. major-infected macrophages. The presence of B-1 cells also favors the production of lipid bodies by infected macrophages. In contrast, we failed to obtain the same effect on parasite replication inside L. major-infected macrophages when the B-1 cells were isolated from IL-10 knockout mice. Our results show that elevated levels of PGE2 and IL-10 produced by B-1 cells increase L. major growth, as indicated by the number of parasites in cell cultures.


Preparation of 6-thioguanosine phosphoramidite for oligoribonucleotide synthesis.
6-Thioguanosine phosphoramidite was prepared, using 2,4-dinitrophenyl as protection group for thio-function, and its stability towards conditions of RNA synthesis was investigated. The results show that the monomer was stable under the conditions of RNA synthesis and suitable for incorporation of thioguanine into oligoribonucleotides.


Should we measure the individual or the system? Operational factors affecting compliance with treatment.
Chronic kidney disease requires a complex array of treatment interventions, including dietary and fluid restriction, medications, and self-monitoring of blood pressure. Patient well-being is directly linked to adhering to physician recommendations and treatment schedules. While considerable efforts have been directed to understanding the contribution of patient characteristics, burden of treatment, and patient-provider relations, little study has been conducted on the "system" requirements that support good patient-provider communication. This study examines how operational characteristics occurring at the time of an encounter affect the likelihood a patient will "hear" provider recommendations.


Direct and indirect fiber-reinforced fixed partial dentures: case reports.
Direct and indirect fiber-reinforced resin composite fixed partial dentures are a new way to produce minimally invasive, esthetic, and cost-effective metal-free tooth replacements. These treatment alternatives have a number of indications, for example, chairside tooth replacements, long-term provisional fixed partial dentures, economically feasible tooth replacements for patients who cannot afford more traditional treatment regimens, and tooth replacements for medically compromised patients who are unable to withstand the physical stress associated with fabrication of traditional fixed prostheses. This article presents four typical cases in which fiber-reinforced fixed partial dentures seemed to be the preferable treatment modality.


Deterministic hydrodynamics: taking blood apart.
We show the fractionation of whole blood components and isolation of blood plasma with no dilution by using a continuous-flow deterministic array that separates blood components by their hydrodynamic size, independent of their mass. We use the technology we developed of deterministic arrays which separate white blood cells, red blood cells, and platelets from blood plasma at flow velocities of 1,000 microm/sec and volume rates up to 1 microl/min. We verified by flow cytometry that an array using focused injection removed 100% of the lymphocytes and monocytes from the main red blood cell and platelet stream. Using a second design, we demonstrated the separation of blood plasma from the blood cells (white, red, and platelets) with virtually no dilution of the plasma and no cellular contamination of the plasma.


Options for addressing exocrine pancreatic insufficiency in patients receiving enteral nutrition supplementation.
Patients with exocrine pancreatic insufficiency (EPI) have suboptimal secretion of pancreatic digestive enzymes and experience a range of clinical symptoms related to the malabsorption of fat. In patients with EPI unable to meet their nutritional requirements, enteral nutrition (EN) support is used to augment nutritional status. In addition to protein and carbohydrate, EN formulas contain fats as a calorie source, as well as vitamins and minerals to help prevent nutritional deficiencies related to malabsorption. Semielemental enteral nutrition formulas are advantageous as they contain hydrolyzed protein, shorter chain carbohydrates, and may contain medium chain triglycerides as a fat source. However, severely pancreatic insufficient patients may be unable to absorb complex long-chain triglycerides provided by EN formulas due to insufficient pancreatic lipase; replacement pancreatic enzyme products are recommended for these patients. Currently, none of the FDA-approved pancreatic enzyme replacement therapy (PERT) products are indicated for use in patients receiving enteral nutrition and administration of enzymes by mixing into enteral nutrition formula is not supported by guidelines as this route is associated with risks. RELiZORB (immobilized lipase) is a novel in-line digestive cartridge that has been designed to address the unmet need for PERT in patients receiving enteral nutrition. RELiZORB efficacy and compatibility with a range of commercially available polymeric and semielemental formulas with varying nutrient, caloric content, and triglyceride chain lengths have been demonstrated. In most formulas, RELiZORB efficiently hydrolyzed greater than 90% of fats within the formula into absorbable fatty acids and monoglycerides.


Clinical and Molecular Spectrum of Glutamate Dehydrogenase Gene Defects in 26 Chinese Congenital Hyperinsulinemia Patients.
To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 μmol/L (range: 37-190 μmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.


Clarification of the oxidation state of cobalt corroles in heterogeneous and homogeneous catalytic reduction of dioxygen.
Co(III) corroles were investigated as efficient catalysts for the reduction of dioxygen in the presence of perchloric acid in both heterogeneous and homogeneous systems. The investigated compounds are (5,10,15-tris(pentafluorophenyl)corrole)cobalt (TPFCor)Co, (10-pentafluorophenyl-5,15-dimesitylcorrole)cobalt (F 5PhMes 2Cor)Co, and (5,10,15-trismesitylcorrole)cobalt (Mes 3Cor)Co, all of which contain bulky substituents at the three meso positions of the corrole macrocycle. Cyclic voltammetry and rotating ring-disk electrode voltammetry were used to examine the catalytic activity of the compounds when adsorbed on the surface of a graphite electrode in the presence of 1.0 M perchloric acid, and this data is compared to results for the homogeneous catalytic reduction of O 2 in benzonitrile containing 10 (-2) M HClO 4. The corroles were also investigated as to their redox properties in nonaqueous media. A reversible one-electron oxidation occurs at E 1/2 values between 0.42 and 0.89 V versus SCE depending upon the solvent and number of fluorine substituents on the compounds, and this is followed by a second reversible one-electron abstraction at E 1/2 = 0.86 to 1.18 V in CH 2Cl 2, THF, or PhCN. Two reductions of each corrole are also observed in the three solvents. A linear relationship is observed between E 1/2 for oxidation or reduction and the number of electron-withdrawing fluorine groups on the compounds, and the magnitude of the substituent effect is compared to what is observed in the case of tetraphenylporphyrins containing meso -substituted C 6F 5 substituents. The electrochemically generated forms of the corrole can exist with Co(I), Co(II), or Co(IV) central metal ions, and the site of the electron-transfer in each oxidation or reduction of the initial Co(III) complex was examined by UV-vis spectroelectrochemistry. ESR characterization was also used to characterize singly oxidized (F 5PhMes 2Cor)Co, which is unambiguously assigned as a Co(III) radical cation rather than the expected Co(IV) corrole with an unoxidized macrocyclic ring.


Posttraumatic stress disorder and family functioning in adolescent cancer.
Twenty three adolescents with a history of cancer, 27 physically abused adolescents, and 23 healthy, nonabused adolescents were administered structured posttraumatic stress disorder (PTSD) interviews and self-report questionnaires regarding family functioning. Thirty five percent of adolescent cancer subjects met criteria for lifetime PTSD as compared to only 7% of the abused adolescents: 17% of the cancer subjects and 11% of the abuse subjects met criteria for current PTSD. Adolescents with cancer viewed their mothers and fathers as significantly more caring and more protective than the comparison and abused adolescents. Cancer subjects who met criteria for lifetime PTSD saw their families as significantly more chaotic than those who did not have PTSD. Eighty three percent of cancer subjects who had lifetime PTSD also had mothers who had PTSD.


An association of hardness of water with incidence of fatty liver syndrome in laying hens.
Twenty-one samples of water were collected from commercial egg production farms in Georgial with or without a history of fatty liver syndrome. These samples plus a sample of water from the University of Georgia Poultry Farm were analyzed for various mineral elements by atomic absorption, direct reading emission spectroscopy and by neutron activation. Water samples from farms with a history of fatty liver syndrome had signficantly more calcium, magnesium, strontium, sodium, iron and barium than water samples from farms reporting no significant problem with fatty liver syndrome. Levels of manganese, boron, copper zinic and aluminum were not significantly different. Although the results do not prove that water quality is the cause of the disease, they do demonstrate an association of hardness of water with fatty liver syndrome that should be further investigated.


MCL1 is phosphorylated in the PEST region and stabilized upon ERK activation in viable cells, and at additional sites with cytotoxic okadaic acid or taxol.
BCL2 family members are subject to regulation at multiple levels, providing checks on their ability to contribute to tumorigenesis. However, findings on post-translational BCL2 phosphorylation in different systems have been difficult to integrate. Another antiapoptotic family member, MCL1, exhibits a difference in electrophoretic mobility upon phosphorylation induced by an activator of PKC (12-O-tetradecanoylphorbol 13-acetate; TPA) versus agents that act on microtubules or protein phosphatases 1/2A. A multiple pathway model is now presented, which demonstrates that MCL1 can undergo distinct phosphorylation events - mediated through separate signaling processes and involving different target sites - in cells that remain viable in the presence of TPA versus cells destined to die upon exposure to taxol or okadaic acid. Specifically, TPA induces phosphorylation at a conserved extracellular signal-regulated kinase (ERK) site in the PEST region (Thr 163) and slows turnover of the normally rapidly degraded MCL1 protein; however, okadaic acid and taxol induce ERK-independent MCL1 phosphorylation at additional discrete sites. These findings add a new dimension to our understanding of the complex regulation of antiapoptotic BCL2 family members by demonstrating that, in addition to transcriptional and post-transcriptional regulation, MCL1 is subject to multiple, separate, post-translational phosphorylation events, produced in living versus dying cells at ERK-inducible versus ERK-independent sites.


Smoking correlates among Inuit men and women in Inuit Nunangat.
Although rates of daily smoking among Inuit have been decreasing since 1991, Inuit are still much more likely to smoke relative to the Canadian population as a whole. However, little population-based empirical research has identified characteristics associated with cigarette use among this population. Based on data from the 2012 Aboriginal Peoples Survey, sex-specific logistic regression analyses, informed by an Inuit social determinants of health framework, described associations between current smoking and selected socio-demographic characteristics among Inuit men and women aged 18 or older who resided in Inuit Nunangat. In 2012, 75% of Inuit men and 74% of Inuit women reported that they smoked cigarettes either daily or occasionally. Inuit men and women had lower odds of smoking if they were high school graduates. Among Inuit men, the odds of smoking were lower for those in higher-income households. Among Inuit women, the odds of smoking were lower for those who had postsecondary education or lived in food-secure households; odds were higher for women who had attended a residential school. Inuit of both sexes had significantly higher odds of smoking if they lived in crowded conditions or in homes where a regular smoker was present. Some correlates of smoking among Inuit in Inuit Nunangat appear to be sex-specific. Findings from this study identify some of the protective and risk factors for smoking among this population and can help inform smoking prevention and cessation programs.


Nutritional issues and therapy in inflammatory bowel disease.
Nutritional issues in inflammatory bowel disease (IBD) often receive inadequate attention both in regard to therapy and nutritionally related complications of IBD. This article reviews much of the research that has evaluated the role of diet in the causation, primary treatment, and adjunctive therapy of both ulcerative colitis (UC) and Crohn's disease (CD). Benefits have been demonstrated in the use of elemental diets or polymeric diets in CD in both acute flare up or maintenance of IBD. A careful team approach can overcome problems in implementing nutritional therapy. Nutrition also has a critical benefit in postoperative CD and perioperative UC. Numerous easily corrected, nutritional abnormalities are often overlooked in patients with IBD, which may have significant consequences. Nutritional therapy may have a central place in the hierarchy of treatment in IBD and further research is critical in this area to better define the benefits of nutrition in IBD.


Rotating point spread function via pupil-phase engineering.
A simple approach based on the use of a properly designed pupil-phase profile can yield a 3D point-spread function (PSF) that rotates with changing defocus, while keeping its transverse shape approximately invariant over ±3-4 waves of defocus. Unlike Gauss-Laguerre mode-based approaches, it generalizes readily for encoding spherical aberration too via PSF rotation.


Centriolar subdistal appendages promote double-strand break repair through homologous recombination.
The centrosome is a cytoplasmic organelle with roles in microtubule organization that has also been proposed to act as a hub for cellular signaling. Some centrosomal components are required for full activation of the DNA damage response. However, whether the centrosome regulates specific DNA repair pathways is not known. Here, we show that centrosome presence is required to fully activate recombination, specifically to completely license its initial step, the so-called DNA end resection. Furthermore, we identify a centriolar structure, the subdistal appendages, and a specific factor, CEP170, as the critical centrosomal component involved in the regulation of recombination and resection. Cells lacking centrosomes or depleted for CEP170 are, consequently, hypersensitive to DNA damaging agents. Moreover, low levels of CEP170 in multiple cancer types correlate with an increase of the mutation burden associated with specific mutational signatures and a better prognosis, suggesting that changes in CEP170 can act as a mutation driver but could also be targeted to improve current oncological treatments.


Highly stretchable patternable conductive circuits and wearable strain sensors based on polydimethylsiloxane and silver nanoparticles.
Patterned circuits on highly stretchable conductive films are critical in the practical application of next-generation flexible and wearable devices. Currently, most patterned circuits do not exhibit highly stretchable properties, and a lithography process in vacuum is required. In this study, silver nanoparticles (AgNPs) and liquid polydimethylsiloxane (PDMS) are mixed together to form liquid conductive adhesives (CAs). Various stretchable patterned circuits are prepared using this CA to achieve all required functions. Six basic patterns, including rhombus, straight lines, serpentine, triangle, ellipses, and fold line, are studied for their stretchable and electrical properties. The film is found to maintain excellent conductivity after withstanding tensile strain of up to 320% and more than 10 000 stretching-releasing cycles of 0%-150%. More than 86% of visible lights can be penetrated through the film due to the transparent substrates. Functional and wearable devices are manufactured, and devices fabricated from rhombus-pattern circuits are found to exhibit stable electrical conductivity when subjected to very high tensile strains. According to the sensitivity of the straight-line patterned circuit to strain, a repeatable use sensitive strain sensor is studied. Also, two types of artificial electrical skin are demonstrated.


Lung-Derived Exosomal miR-483-3p Regulates the Innate Immune Response to Influenza Virus Infection.
Exosomes regulate cell-cell communication by transferring functional proteins and RNAs between cells. Here, to clarify the function of exosomes during influenza virus infection, we characterized lung-derived exosomal microRNAs (miRNAs). Among the detected miRNAs, miR-483-3p was present at high levels in bronchoalveolar lavage fluid (BALF) exosomes during infection of mice with various strains of influenza virus, and miR-483-3p transfection potentiated gene expression of type I interferon and proinflammatory cytokine upon viral infection of MLE-12 cells. RNF5, a regulator of the RIG-I signaling pathway, was identified as a target gene of miR-483-3p. Moreover, we found that CD81, another miR-483-3p target, functions as a negative regulator of RIG-I signaling in MLE-12 cells. Taken together, this study indicates that BALF exosomal miRNAs may mediate the antiviral and inflammatory response to influenza virus infection.


Current status and challenges in uterine myometrial tissue engineering.
The uterus undergoes significant modifications throughout pregnancy to support embryo development and fetal growth. However, conditions like fibroids, adenomyosis, cysts, and C-section scarring can cause myometrial damage. The importance of the uterus and the challenges associated with myometrial damage, and the need for alternative approaches are discussed in this review. The review also explores the recent studies in tissue engineering, which involve principles of combining cells, scaffolds, and signaling molecules to create functional uterine tissues. It focuses on two key approaches in uterine tissue engineering: scaffold technique using decellularized, natural, and synthetic polymer and 3D bioprinting. These techniques create supportive structures for cell growth and tissue formation. Current treatment options for myometrial damage have limitations, leading to the exploration of regenerative medicine and integrative therapies. The review emphasizes the potential benefits of tissue engineering, including more effective and less invasive treatment options for myometrial damage. The challenges of developing biocompatible materials and optimizing cell growth and differentiation are discussed. In conclusion, uterine tissue engineering holds promise for myometrial regeneration and the treatment of related conditions. This review highlights the scientific advancements in the field and underscores the potential of tissue engineering as a viable approach. By addressing the limitations of current treatments, tissue engineering offers new possibilities for improving reproductive health and restoring uterine functionality. Future research shall focus on overcoming challenges and refining tissue engineering strategies to advance the field and provide effective solutions for myometrial damage and associated disorders.


Fibroblast Growth Factor 1-Transfected Adipose-Derived Mesenchymal Stem Cells Promote Angiogenic Proliferation.
The aim of this study was to investigate, for the first time, the effects of using adipose-derived mesenchymal stem cells (AD-MSCs) transfected with an episomal plasmid encoding fibroblast growth factor 1 (FGF1) (AD-MSCsFGF1), in providing the microenvironment required for angiogenic proliferation. The isolated rat AD-MSCs were positive for mesenchymal (CD29 and CD90) and negative for hematopoietic (CD34 and CD45) surface markers. Adipogenic and osteogenic differentiation of the AD-MSCs also occurred in the proper culture media. The presence of FGF1 in the conditioned medium from the AD-MSCsFGF1 was confirmed by Western blotting. G418 and PCR were used for selection of transfected cells and confirmation of the presence of FGF1 mRNA, respectively. Treatment with the AD-MSCFGF1-conditioned medium significantly increased the NIH-3T3 cell proliferation and human umbilical vein endothelial cell (HUVEC) tube formation compared to conditioned medium from nontransfected AD-MSCs (p < 0.001). In conclusion, the AD-MSCsFGF1 efficiently secreted functional FGF1, which promoted angiogenic proliferation. Using AD-MSCsFGF1 may provide a useful strategy in cell therapy, which can merge the beneficial effects of stem cells with the positive biological effects of FGF1 in various disorders, especially tissue defects, neurodegenerative, cardiovascular and diabetes endocrine pathologies, which remain to be tested in preclinical and clinical studies.


Anticancer effects of the microbiome and its products.
The human gut microbiome modulates many host processes, including metabolism, inflammation, and immune and cellular responses. It is becoming increasingly apparent that the microbiome can also influence the development of cancer. In preclinical models, the host response to cancer treatment has been improved by modulating the gut microbiome; this is known to have an altered composition in many diseases, including cancer. In addition, cancer treatment with microbial agents or their products has the potential to shrink tumours. However, the microbiome could also negatively influence cancer prognosis through the production of potentially oncogenic toxins and metabolites by bacteria. Thus, future antineoplastic treatments could combine the modulation of the microbiome and its products with immunotherapeutics and more conventional approaches that directly target malignant cells.


Assessing the acceptability of incentivising HPV vaccination consent form return as a means of increasing uptake.
Uptake of human papillomavirus (HPV) vaccination is high overall but there are disparities in uptake, particularly by ethnicity. Incentivising vaccination consent form return is a promising approach to increase vaccination uptake. As part of a randomised feasibility trial we qualitatively assessed the acceptability of increasing uptake of HPV vaccination by incentivising consent form return. In the context of a two-arm, cluster randomised feasibility trial, qualitative free-text questionnaire responses were collected from adolescent girls (n = 181) and their parents (n = 61), assessing the acceptability of an incentive intervention to increase HPV vaccination consent form return. In the incentive intervention arm, girls who returned a signed consent form (regardless of whether consent was given or refused), had a 1-in-10 chance of winning a £50 shopping voucher. Telephone interviews were also conducted with members of staff from participating schools (n = 6), assessing the acceptability of the incentive. Data were analysed thematically. Girls and parents provided a mix of positive, negative and ambivalent responses about the use of the incentive to encourage HPV vaccination consent form return. Both girls and parents held misconceptions about the nature of the incentive, wrongly believing that the incentive was dependent on vaccination receipt rather than consent form return. School staff members also expressed a mix of opinions on the acceptability of the incentive, including perceptions of effectiveness and ethics. The use of an incentive intervention to encourage the return of HPV vaccination consent forms was found to be moderately acceptable to those receiving and delivering the intervention, although a number of changes are required to improve this. In particular, improving communication about the nature of the incentive to reduce misconceptions is vital. These findings suggest that incentivising consent form return may be an acceptable means of improving HPV vaccination rates, should improvements be made. ISRCTN Registry; ISRCTN72136061 , 26 September 2016, retrospectively registered.


Progressive oculo-orofacial-speech apraxia (POOSA).
A loss of speech can be related to disorders of the motor units (paresis), language deficits (aphasia), or speech programming deficits (apraxia of speech). Although apraxia of speech has been reported to be associated with degenerative diseases, we observed a patient with a unique constellation of signs that included apraxia of speech, oculo-orofacial apraxia and a supranuclear ophthalmoplegia in the absence of extrapyramidal (Parkinsonian) signs. Post-mortem examination revealed a loss of neurons in the frontal and temporal regions, but there was also a marked loss of neurons and astrogliosis in the caudate, claustrum, globus pallidus, substantia nigra, and loss of axons in the anterior cerebral peduncles. This patient's clinical presentation and the pathological correlates suggest that he might have suffered with a distinct disorder we call progressive oculo-orofacial-speech apraxia or POOSA.


[Two cases of surgically treated triple cancer].
Two cases of surgically treated triple cancer are reported. Case 1: Three tumors, one in the lung, one in the stomach, and one in the colon of a 74-year-old man were diagnosed preoperatively. First a subtotal gastrectomy and transverse colectomy were performed and, second 27 days later, a lobectomy of the lower left lung. Pathologically, each tumor proved to be a primary sion. Case 2: A 70-year-old woman, treated surgically for left breast cancer 5 years ago, was found to have anemia. Gastric endoscopy showed a cancer in the antrum. A subtotal gastrectomy was performed. Intraoperatively another tumor in the cecum was found and a right hemicolectomy was also performed. Pathologically each tumor was a primary lesion.


Preliminary explorations of the role of mitochondrial proteins in refractory epilepsy: some findings from comparative proteomics.
Approximately 20-30% of patients with epilepsy continue to have seizures despite carefully monitored treatment with antiepileptic drugs. The mechanisms that underlie why some patients are responsive and others prove resistant to antiepileptic drugs are poorly understood. Increasing evidence supports a role for altered mitochondrial function in the pathogenesis of epilepsy. To gain greater molecular insight in the pathogenesis of intractable epilepsy, we undertook a global analysis of protein expressions in a pharmacoresistant epileptic model selected by phenytoin in electrical amygdala-kindled rats by using two-dimensional gel electrophoresis coupled with matrix-assisted laser desorption/ionization time of flight (MALDI-TOF-TOF). We identified five increased proteins and 14 decreased proteins including voltage-dependent anion channel 1 (VDAC1) with a 2.82-fold increased level (P < 0.05) and voltage-dependent anion channel 2 (VDAC2) with a 3.97-fold decreased level (P < 0.05) in hippocampus of pharmacoresistant rats. The increased VDAC1 and decreased VDAC2 were confirmed by Western blot analysis and immunohistochemistry. Vascular mitochondria and apoptosis neurons were observed through electron microscopy. Energy contents, the adenine nucleotides, were measured by high-performance liquid chromatography (HPLC). The correlation analyses were carried out between VDAC and the energy charge. These findings indicate that the increase of VDAC1 and the decrease of VDAC2 play an important role during the process and provide new molecular evidence in understanding mechanism of refractory epilepsy.


Surface acoustic wave nebulization device with dual interdigitated transducers improves SAWN-MS performance.
We compared mass spectrometric (MS) performance of surface acoustic wave nebulization (SAWN) generated by a single interdigitated transducer (IDT) designed to produce a progressive wave (PW) to one with a dual IDT that can in theory generate standing waves (SW). Given that devices using dual IDTs had been shown to produce fewer large size droplets on average, we hypothesized they would improve MS performance by improving the efficiency of desolvation. Indeed, the SW-SAWN chip provided an improved limit of detection of 1 femtomole of peptide placed on chip making it 100× more sensitive than the PW design. However, as measured by high-speed image recording and phase Doppler particle analyzer measurements, there was only a 26% increase in the small diameter (1-10 µm) droplets produced from the new device, precluding a conclusion that the decrease in droplet size was solely responsible for the improvement in MS signal/noise. Given that the dual IDT design produced a more instantaneous plume than the PW design, the more likely contributor to improved MS signal/noise was concluded to be a higher ion flux entering the mass spectrometer for the dual IDT designs. Notably, the dual IDT device allowed production of much higher quality protein mass spectra up to about 20 kDa, compared with the single IDT device. Copyright © 2016 John Wiley & Sons, Ltd.


Relationship between immunoglobulin allotypes and susceptibility to nasopharyngeal carcinoma in Malaysia.
The relationship between immunoglobulin allotypes and risk of developing nasopharyngeal carcinoma was examined in a comparative study of 50 Chinese cases and 140 Chinese controls and 50 Malay cases and 79 Malay controls residing in Malaysia. Although the most common Gm phenotype was elevated in both Chinese and Malay nasopharyngeal carcinoma patients compared to their controls, there were no significant differences between cases and controls in the distribution of Gm haplotypes in either population. There were no differences between cases and controls in the distribution of Km alleles in either population. Thus a previously reported association of Km(1) with increased nasopharyngeal carcinoma risk in Tunisia is not confirmed in two Mongoloid populations in Malaysia.


Optimization of speech processor fitting strategies for Chinese-speaking cochlear implantees.
To compare speech recognition performance in Chinese-speaking cochlear implant patients with a speech processor program selected by the clinical audiologist in Taiwan and with a new speech processor program based on the Washington University clinical procedure developed by Skinner et al. Six adult Chinese-speaking patients implanted with the Nucleus cochlear implant system participated in this study. A fitting procedure developed in 1995 by Skinner et al. at Washington University School of Medicine was used to create a new speech processor program to optimize each patient's hearing in everyday life. Speech tests (vowels, consonants, tones, and words), sound-field thresholds, and a self-report questionnaire were used to evaluate each patient's performance with his or her previous speech processor program and a new one. Four of the six patients had significant changes from the previous to the new speech processor program. These changes were associated with improvement in score on at least one speech test, more sensitive sound field thresholds, and reported improvement in some everyday listening situations on the questionnaire. These results suggest that use of this procedure with adult cochlear implantees may improve benefit in everyday life. Analysis of the speech test stimuli and patients' responses provides a basis for modification or creation of new Mandarin Chinese speech tests for preoperative and postoperative evaluation of adult cochlear implant patients.


Envisioning nursing in 2050 through the eyes of nurse theorists: Rosemarie Rizzo Parse and Martha E. Rogers.
Rosemarie Rizzo Parse and Rogerian scholar, Violet Malinski, on behalf of Martha E. Rogers, envision how their respective theoretical ideas will be expressed in 2050. Parse introduces several changes highlighting the idea of indivisible cocreation in the ontology of the humanbecoming school of thought and concomitant changes in the wording of its principles. Notions of human freedom and dignity will be extremely important given increasingly mechanized healthcare. Malinski describes Rogerian formulations for practice and research that will continue to facilitate well-being for humankind and the environment. She also addresses challenges and opportunities for an evolving science of unitary human beings.


Maladaptive cognitive emotion regulation strategies and positive symptoms in schizophrenia spectrum disorders: The mediating role of global emotion dysregulation.
Previous studies have identified a positive association between maladaptive cognitive emotion regulation strategies and positive symptoms (e.g., hallucinations and delusions) among patients with schizophrenia spectrum disorders. However, translating this finding to clinical practice is challenging. Some patients are reported to experience difficulties in correcting the use of maladaptive cognitive emotion regulation strategies in psychological therapy, which may be due to an underlying effect of global emotion dysregulation. Therefore, the present study aimed to determine the mediating or moderating role of global emotion dysregulation in the relationship between maladaptive cognitive emotion regulation strategies and positive symptoms. A total of 123 newly diagnosed patients with schizophrenia spectrum disorders completed self-report measures of maladaptive cognitive emotion regulation strategies (rumination, catastrophic thinking, self-blame, other-blame) and global emotion dysregulation. The severity of positive symptoms was rated on the Brief Psychiatric Rating Scale-Expanded. Mediation and moderation analyses were performed to test the hypothesized models. Mediation analysis revealed that global emotion dysregulation mediated the relationship between maladaptive cognitive emotion regulation strategies and positive symptoms after controlling for age, gender, ethnicity, duration of untreated psychosis, medication dosage, psychiatric comorbidities, and family history of mental illness (R2 = 23.3%, moderate effect size = 0.30). There was no moderating effect of global emotion dysregulation. The present study presents preliminary evidence on the mediating role of global emotion dysregulation in the relationship between maladaptive cognitive emotion regulation strategies and positive symptoms in schizophrenia spectrum disorders. This finding adds to our current understanding on emotion regulation phenomena in schizophrenia spectrum disorders.


Resolution of sterile inflammation: role for vitamin C.
Macrophage reprogramming is vital for resolution of acute inflammation. Parenteral vitamin C (VitC) attenuates proinflammatory states in murine and human sepsis. However information about the mechanism by which VitC regulates resolution of inflammation is limited. To examine whether physiological levels of VitC modulate resolution of inflammation, we used transgenic mice lacking L-gulono-γ-lactone oxidase. VitC sufficient/deficient mice were subjected to a thioglycollate-elicited peritonitis model of sterile inflammation. Some VitC deficient mice received daily parenteral VitC (200 mg/kg) for 3 or 5 days following thioglycollate infusion. Peritoneal macrophages harvested on day 3 or day 5 were examined for intracellular VitC levels, pro- and anti-inflammatory protein and lipid mediators, mitochondrial function, and response to lipopolysaccharide (LPS). The THP-1 cell line was used to determine the modulatory activities of VitC in activated human macrophages. VitC deficiency significantly delayed resolution of inflammation and generated an exaggerated proinflammatory response to in vitro LPS stimulation. VitC sufficiency and in vivo VitC supplementation restored macrophage phenotype and function in VitC deficient mice. VitC loading of THP-1 macrophages attenuated LPS-induced proinflammatory responses. VitC sufficiency favorably modulates macrophage function. In vivo or in vitro VitC supplementation restores macrophage phenotype and function leading to timely resolution of inflammation.


HIV-disclosure in the context of vertical transmission: HIV-positive mothers in Johannesburg, South Africa.
HIV-disclosure among childbearing women remains poorly understood, particularly in sub-Saharan Africa. This paper chronicles disclosure experiences of 31 women attending prevention of mother-to-child HIV transmission services in Johannesburg. Data collection entailed repeat in-depth interviews over a nine-month period. Virtually all women (93.5%) had told at least one person (usually a partner), most voluntarily and within a week of the test result. Secondary disclosure was most likely with female family members, through indirect means and involuntary. Confidentiality breach by primary targets likely contributed to the observed high rates of involuntary secondary disclosure and negative secondary disclosure experiences. For most mothers, voluntary disclosure was driven by the desire to ensure adequate infant care and avoid vertical HIV transmission. The impact of disclosure was not always clear-cut. While most primary disclosure experiences were ultimately constructive, secondary disclosure more likely led to rejection, stigmatization and the withholding of financial support. Our data illustrate the influence of social contextual factors on disclosure patterns and impact. For these mothers, socio-cultural norms, the current media and political environment surrounding HIV/AIDS, household composition and social networks and childbearing status shaped disclosure experiences; sometimes constraining disclosure circumstances and sometimes creating a safe space to disclose. Programmatic implications are also discussed.


Care for patients undergoing extracorporeal photopheresis to treat chronic graft-versus-host disease: review of the evidence.
Late immune dysregulation following allogeneic hematopoietic cell transplantation (HCT) is known as chronic graft-versus-host disease (GVHD), which is a major cause of mortality and morbidity after HCT, and a rise in its incidence is predicted. Better therapies are being sought to manage chronic GVHD and limit patients' exposure to corticosteroids. Extracorporeal photopheresis (ECP), an immune-modulating therapy, has shown preliminary safety and efficacy in treating chronic GVHD. However, access to ECP is limited, care is costly, and the optimal frequency, duration, and durability of response are unknown. Although nurses who care for patients with chronic GVHD recognize its adverse impact on patients' quality of life, limited evidence exists about the selection of patients most likely to benefit from ECP therapy and from the supportive care provided to them. A multidisciplinary approach is needed to define the desired outcomes of ECP therapy and to determine the evidence base for nursing management approaches.


Widespread Use of Prescription Nonsteroidal Anti-Inflammatory Drugs Among U.S. Army Active Duty Soldiers.
Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat pain and inflammation by inhibiting prostaglandin synthesis. There is a high incidence of musculoskeletal injuries in the military, which would validate the widespread use of NSAIDs. This study determined the amount and specific types of NSAIDs being prescribed to U.S. Army active duty soldiers. This study was a quantitative study which utilized an existing database of de-identified data; therefore, institutional review board approval was not required. Data pertaining to NSAID prescriptions issued to active duty soldiers for fiscal years 2006, 2011, and 2014 were obtained from the Department of Defense Pharmacy Data Transactions Service data warehouse, which contains all outpatient prescriptions. The data include the number of soldiers receiving NSAID prescriptions (i.e., utilizers) as well as the number of prescriptions given for each specific NSAID. In 2006, 2011, and 2014, the numbers of active duty utilizers were 348,031, 435,364, and 418,579, respectively. For the entire active duty Army, the percentage of soldiers who were receiving NSAID prescriptions was approximately 69% in 2006, 77% in 2011, and 82% in 2014. The number of NSAIDs prescribed was 740,090 in 2006; 898,291 in 2011; and 857,964 in 2014. Celecoxib, the only cyclooxygenase-2 inhibitor prescribed in the United States accounted for 2.4% of these NSAID prescriptions in 2006, 6.3% in 2011, and 7.1% in 2014. During all 3 years, the number of prescriptions filled was almost twice the number of utilizers, indicating that many individuals were receiving more than one prescription. Female soldiers received almost twice the number of prescriptions per individual as male soldiers. The use of over-the-counter NSAIDs, which are widely available, was not accounted for in this study; therefore, total NSAID use is likely higher than reported. The vast majority of U.S. Army active duty soldiers are being prescribed NSAIDs. These data raise concerns because of the potential adverse effects that NSAIDs have on gastrointestinal, renal, and cardiovascular function, as well as bone health. Additional studies are warranted to determine the actual amounts of NSAIDs being used and the specific conditions for which they are being prescribed.


ATP sensitive potassium channels are involved in adenosine A2 receptor mediated coronary vasodilatation in the dog.
The aim was to determine a role of ATP sensitive potassium (KATP) channels in adenosine A2 receptor mediated coronary vasodilatation in anaesthetised dogs in vivo. Coronary blood flow in the left circumflex coronary artery, aortic pressure, and left ventricular pressure were measured during intracoronary infusions of the drugs into the left circumflex artery. A non-selective A2 receptor agonist NECA (5'-N-ethylcarboxamidoadenosine) at 10(-10)-10(-8) mol.min-1 before and after an A1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine) increased coronary blood flow in a dose dependent manner, without affecting other haemodynamic variables. Glibenclamide at 10 micrograms.kg-1.min-1, which did not alter baseline haemodynamic variables, markedly inhibited the increases in coronary blood flow caused by NECA alone and after DPCPX (p < 0.01). A non-selective adenosine receptor antagonist 8-phenyltheophylline abolished the NECA induced increases in coronary blood flow after DPCPX. These results suggest that A2 receptor mediated coronary vasodilatation was mediated largely by opening of KATP channels. Glibenclamide did not alter the increase in coronary blood flow evoked by forskolin or acetylcholine, suggesting that KATP channels may not be involved in coronary vasodilatation induced by activation of adenylate cyclase or guanylate cyclase. Furthermore, DPCPX increased basal coronary blood flow, which was blocked by 8-phenyltheophylline and by glibenclamide, suggesting that it may have unmasked A2 receptor mediated coronary vasodilatation by inhibiting the A1 receptor mediated vasoconstricting action of endogenous adenosine. Opening of KATP channels may be involved importantly in adenosine A2 receptor mediated coronary vasodilatation in canine hearts.


[Glomus tumors. Clinical, histological and immunohistochemical study. Apropos of 29 cases].
This retrospective pathological study, based on twenty-nine glomus tumors, was conducted in order to define the histological or immunohistochemical diagnostic criteria in cases with atypical morphology. The immunohistochemical phenotype of glomus tumors was defined by means of identification of glomus cells, vessels and associated nerve fibres.


Epigallocatechin Gallate Attenuates Hip Fracture-Induced Acute Lung Injury by Limiting Mitochondrial DNA (mtDNA) Release.
BACKGROUND To study the protective effects and explore the mechanism of epigallocatechingallate (EGCG) on the hip fracture-induced acute lung injury. MATERIAL AND METHODS Thirty male Sprague-Dawley (SD) rats were randomly divided into the control group, hip fracture group, and hip fracture + EGCG (10 mg/Kg) group. After 24 h, blood samples, bronchoalveolar lavage fluid (BALF), and lung tissue were collected. Serum mitochondrial DNA (mtDNA) was measured by RT-PCR and BALF was used to perform cytological analysis and enzyme-linked immunosorbent assay (ELISA) assay. Lung tissue was used to evaluate the injury level. RESULTS EGCG significantly reduced the hip fracture-induced high level of serum mtDNA (p<0.05). HE staining showed protective effects of EGCG. Lower lung injury score and wet/dry ratio were identified in the hip fracture + EGCG group than in the hip fracture group (p<0.05). We found significantly lower levels of infiltration of inflammatory cells and production of inflammatory cytokines in the BALF of the hip fracture + EGCG group than in the hip fracture group (p<0.05). CONCLUSIONS Our study found that EGCG had protective effects on hip fracture-induced acute lung injury and suggests that EGCG exerts its protective effects through limiting the release of mtDNA. Our results provide a novel pharmacological agent to attenuate hip fracture-induced acute lung injury, as well as a potential theory to better explain the anti-inflammatory property of EGCG.


Review of the Varilrix varicella vaccine.
Varicella zoster virus causes an acute infection that affects most children globally, but the age of infection can be greater in residents of tropical areas. It has generally been considered a mild disease, although there are accumulating data to show that it can cause significant morbidity and mortality in immunocompetent as well as immunocompromised children and adults. Oka-strain live attenuated varicella vaccines were developed in the 1970s. Varilrix developed by GlaxoSmithKline Biologicals (Rixensart, Belgium), is one of the vaccines produced and marketed in over 80 countries. Similar to the other Oka-strain vaccines, Varilrix is safe, immunogenic and efficacious in both immunocompromised and immunocompetent children and adults.


[Development of an algorithm for the detection of early signs of cerebral ischemia on CT images].
This paper describes an approach to automatically detect the parenchymal hypoattenuation of hyperacute stroke in nonenhanced computed tomography (CT) images. This technique is based on a comparison between the CT values histograms of right and left brains. A subtraction curve that was regarded as an output value was calculated by subtracting the right-hemispherical histogram from the left-hemispherical histogram obtained from one of the region-of-interest (ROI) sets on an image. The output value was used to assess whether hypoattenuation exists on CT images with a threshold value. If judged abnormal, a rectangular region including a whole or partial hypoattenuation area was detected from the ROI. Twenty-six cases with hypoattenuation and 30 cases without hypoattenuation were included in this study. As a result of our experiments, the sensitivity of this method in detecting hypoattenuation was found to be 92%, with approximately 0.16 false-positive per image. Our preliminary experimental results indicated that the proposed technique can be used for the automated detection of parenchymal hypoattenuation of hyperacute stroke on nonenhanced CT images.


Integrated one-day surveillance of antimicrobial use, antimicrobial consumption, antimicrobial resistance, healthcare-associated infection, and antimicrobial resistance burden among hospitalized patients in Thailand.
Surveillance of antimicrobial use (AMU), antimicrobial consumption (AMC), antimicrobial resistance (AMR), healthcare-associated infection (HAI), and AMR burden are usually measured by time-consuming and expensive multiple separate longitudinal surveys. This study aimed to investigate feasibility and benefit of integrated one-day surveillance to estimate and monitor these parameters. Integrated one-day surveillance of AMU, AMC, AMR, HAI, and AMR burden among hospitalized patients in 183 hospitals in Thailand was conducted. Parameter data was collected for each patient who received antibiotic on a survey day. AMU prevalence was 51.5% among 23,686 hospitalized patients. The most commonly used antibiotic for infection prophylaxis and treatment was cefazolin and ceftriaxone, respectively. The most common infection was pneumonia. Community-associated infection (CAI) was observed in 64.9%, and 34.1% had HAI. Prevalence of AMR was highest in A. baumannii infection. AMR in bacteria was more prevalent among HAI than among CAI. Consumption of all antibiotics was 18,103 defined daily doses. HAI prevalence was 14.0%. Health and economic burden were much higher in patients with antibiotic-resistant infection. Integrated one-day surveillance of these important parameters among hospitalized patients is feasible and can be used for estimation and monitoring from the facility-level to the national-level in resource-limited settings.


Intramitochondrial glycogen in hypertrophied infundibular muscle of patients with congenital heart diseases.
A small population of glycogen-containing mitochondria was found in operatively resected myocardium in 8 of 11 patients with various types of congenital heart diseases associated with right ventricular hypertrophy and muscular (infundibular) obstruction to right ventricular outflow. The presence of intramitochondrial glycogen correlated with the degree of peripheral arterial oxygen desaturation but not with the severity of hemodynamic alterations or with the ages of the patients. The occurrence of intramitochondrial glycogen in myocardium in other conditions is reviewed, and its possible pathogenesis is discussed.


An update on renal artery denervation and its clinical impact on hypertensive disease.
Hypertension is a globally prevalent condition, with a heavy clinical and economic burden. It is the predominant risk factor for premature cardiovascular and cerebrovascular disease, and is associated with a variety of clinical disorders including stroke, congestive cardiac failure, ischaemic heart disease, chronic renal failure, and peripheral arterial disease. A significant subset of hypertensive patients have resistant hypertensive disease. In this group of patients, catheter-based renal artery denervation has emerged as a potential therapy, with favourable clinical efficacy and safety in early trials. Additional benefits of this therapy are also being identified and include effects on left ventricular remodeling, cardiac performance, and symptom status in congestive cardiac failure. Utility of renal denervation for the management of resistant hypertension, however, has become controversial since the release of the Symplicity HTN-3 trial, the first large-scale blinded randomised study investigating the efficacy and safety of renal artery denervation. The aim of this paper is to evaluate the history, utility, and clinical efficacy of renal artery denervation technology, including an in-depth appraisal of the current literature and principal trials.


Stability of pBR322-derived plasmids.
The stability of pBR322-derived plasmids was studied during growth of their Escherichia coli host in the absence of antibiotics. Plasmid pBR322, as well as its delta rom and delta bla derivatives, were lost from their host within 60 generations, but a number of delta tet derivatives were quite stable under the same conditions. An evaluation of the data indicated that primary plasmid loss due to random partitioning corresponds to the generation of a plasmid-free cell about every 10(4) divisions (probability P0; = "intrinsic" instability). Secondary loss of plasmid-carrying cells resulted from a growth advantage of the plasmid-free cells when bacteria die, perhaps due to unrepaired lethal damage in the DNA, under conditions of stationary incubation (= "apparent" instability). This cell death also occurred in the absence of plasmids but was accelerated by the presence of extra plasmid DNA in the cell and further accelerated by a functional tet gene. This was the reason for the differential apparent stabilities of delta bla and delta tet plasmids. There was no indication that an accumulation of plasmid multimers contributed to the plasmid instability, as has been suggested in the literature. The value of P0 = 10(-4) is 14 orders of magnitude greater than expected under the assumption of a random (Poisson) distribution of plasmid copy numbers in a population of cells.


Inhibition of angiotensin-converting enzyme by angiotensin I analogue peptide inhibitors. A kinetic study.
Angiotensin I analogues with a phosphonic acid group replacing the C-terminal carboxyl group were shown to be competitive inhibitors of angiotensin-converting enzyme. This new class of inhibitors was used to study the binding requirements of the angiotensin I-like ligands to the enzyme's active site. These studies indicate that angiotensin-converting enzyme recognizes at least five amino acid residues at the C-terminus of the peptide. The effect of pH on the binding of the most potent inhibitor peptide was compared to Captopril. The two inhibitors showed similar Ki-pH profiles despite their structural differences. Chloride enhanced the binding of the peptide inhibitor at both pH 9.0 and pH 6.5. At pH 9.0 the inhibitor peptide and the anion bind randomly to the enzyme, while at pH 6.5 the mechanism is ordered. In the latter case, the anion binds first to the enzyme.


Increased angiogenesis and enhanced bone formation in patients with IgM monoclonal gammopathy and urticarial skin rash: new insight into the biology of Schnitzler syndrome.
Schnitzler syndrome is a rare plasma cell disorder the pathogenesis of which is still not fully understood. We evaluated the circulating levels of four major angiogenic cytokines (VEGF, angiogenin, angiopoietin-1 and angiopoietin-2) and six bone remodeling markers (sRANKL, osteoprotegerin, dickkopf-1, CTX, osteocalcin and bone-specific alkaline phosphatase-bALP) in 13 patients with Schnitzler syndrome. At diagnosis, patients had elevated angiogenic cytokines. The mean VEGF levels were almost 3.5-fold higher in Schnitzler syndrome compared to controls, while 10 of 13 patients had higher VEGF than the upper control value. Successful treatment led to a significant reduction in VEGF. Patients with Schnitzler syndrome had increased bone formation (high bALP, osteocalcin and osteoprotegerin) which was not balanced by an increase in bone resorption (normal CTX and sRANKL). These data support a role for VEGF as a new minor criterion in the diagnosis and follow up of Schnitzler syndrome, while the uncoupling of bone remodeling in favor of bone formation justifies the presence of bone densification.