Nerve fibre proliferation in interstitial cystitis.
The aetiology of pain in interstitial cystitis is not understood, although it has been reported to be due to release of mediators from mast cell granules. Cystolysis and intravesical instillation of dimethyl sulphoxide have been shown to relieve pain in this condition. We have studied the nerve population within the bladder wall using immunohistochemical stains for protein gene product 9.5. A group of 18 cases of chronic interstitial cystitis and 12 controls; neuropathic bladder (n = 1), chronic bacterial cystitis (n = 3), systemic lupus erythematosus cystitis (n = 2) and normals (n = 6), were investigated. There were significantly more nerve fibres within the sub-urothelial and detrusor muscle layers in chronic interstitial cystitis than there were in normals. Patients with chronic cystitis of other aetiology did not have a significant increase in nerve fibre density within the bladder wall suggesting a specific association between nerve fibre proliferation and interstitial cystitis. Cystolysis is shown to deplete selectively the submucosal nerve plexuses without altering the nerve density within detrusor muscle. This finding explains the desensitisation of the bladder without impairment of detrusor function after this procedure.


Urotensin II and urocortin trigger the expression of myostatin, a negative regulator of cardiac growth, in cardiomyocytes.
Urotensin II (UII) and urocortin (UCN) are potent contributors to the physiopathology of heart failure. Our study investigated the effects of UII and UCN on the expression of myostatin (Mstn) in primary culture of adult cardiomyocytes. Adult rat cardiomyocytes were stimulated for 48 h with UII and UCN. Cell size and protein content were determined. Mstn gene expression was determined by real time quantitative polymerase chain reaction. Treatment with UII and UCN stimulates hypertrophy of adult cardiomyocytes. This effect was associated with a twofold increase of Mstn gene expression. We have established for the first time that the two hypertrophic peptides UII and UCN stimulate the expression of Mstn.


Automatic measurement of skin textures of the dorsal hand in evaluating skin aging.
Changes in skin textures have been used to evaluate skin aging in many studies. In our previous study, we built some skin texture parameters, which can be used to evaluate skin aging of human dorsal hand. However, it will take too much time and need to work arduously to get the information from digital skin image by manual work. So, we want to build a simple and effective method to automatically count some of those skin texture parameters by using digital image-processing technology. A total of 100 subjects aged 30 years and above were involved. Sun exposure history and demographic information were collected by using a questionnaire. The skin image of subjects' dorsal hand was obtained by using a portable skin detector. The number of grids, which is one of skin texture parameters built in our previous study, was measured manually and automatically. Automated image analysis program was developed by using Matlab 7.1 software. The number of grids counted automatically (NGA) was significantly correlated with the number of grids counted manually (NGM) (r = 0.9287, P < 0.0001). And in each age group, there were no significant differences between NGA and NGM. The NGA was negatively correlated with age and lifetime sun exposure, and decreased with increasing Beagley-Gibson score from 3 to 6. In addition, even after adjusting for NGA, the standard deviation of grid areas for each image was positively correlated with age, sun exposure, and Bealey-Gibson score. The method introduced in present study can be used to measure some skin aging parameters automatically and objectively. And it will save much time, reduce labor, and avoid measurement errors of deferent investigators when evaluating a great deal of skin images in a short time.


Older age increases short-term surgical complications after primary knee arthroplasty.
Age is a known risk factor for complications after knee arthroplasty; however, age-related risks for a variety of complications of total and partial knee arthroplasties have not been well quantified. Our study addressed three questions to better understand age-related risk of complications: (1) At what age do different types of complications increase? (2) Is the increase in complications with age resulting from age-related patient comorbidities, sociodemographic characteristics, and surgical conditions? (3) What is the probability of complications at different ages for an average patient? The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database from 2005 to 2009 was used to analyze complications for 8950 patients. Complications included NSQIP events, and complications described by the 2003 National Institutes of Health (NIH) consensus statement on total knee arthroplasty as well as 30-day mortality, deep vein thrombosis, return to the operating room, extended length of stay, and technical aspects of the surgery itself. Logistic regression analysis was performed. Mortality was higher for those aged 85 and older. NSQIP complications increased starting at age 70 years and NIH complications at 85 years. Age remained an independent risk factor for multiple complications with controls. The predicted risk for an average patient ranged from 4% (40-64 years old) to 17% (90 years or older) for NSQIP complications and 2.8% to 8.8% for NIH complications. Age is an important independent predictor of surgical complications after knee arthroplasties. Surgeons can share these quantified age-specific risks with patients to guide management decisions.


Role of NK cells in cord blood transplantation and their enhancement by the missing ligand effect of the killer-immunoglobulin like receptor.
Natural killer (NK) cells are the first lymphocytes reconstituted after allogenic hematopoietic stem cell transplantation (HSCT). Especially, in cord blood transplantation (CBT), the increase in the number of NK cells is sustained for a long period. Although there are conflicting results, many studies show that early reconstitution of NK cells is associated with favorable CBT outcomes, suggesting that maximizing NK cell functions could improve the CBT outcome. Killer immunoglobulin-like receptors (KIRs) include inhibitory and stimulatory receptors, which can regulate NK-cell activity. Because some of the KIRs have HLA class I as their ligand, the KIR-ligand interaction on NK cells can be lost in some cases of CBT, which results in the activation of NK cells and alters HSCT outcome. Thus, effects of KIR-ligand mismatch under various conditions have been widely examined; however, the results have been controversial. Among such studies, those using the largest number of CBTs showed that HLA-C2 (KIR2DL1-ligand) mismatches have a favorable effect on the relapse rate and overall survival only when the CBT used methotrexate for graft-versus-host disease prophylaxis. Another study suggested that KIR-ligand mismatch is involved in reducing the relapse of acute myeloid leukemia, mediated by reactivation of cytomegalovirus. These results indicate that activation of NK cells by KIR-ligand mismatch may have favorable effects on CBT outcomes and could help enhance the NK-cell function.


Mefloquine-oxazolidine derivatives: a new class of anticancer agents.
A series of 23 racemic mefloquine-oxazolidine derivatives, 4-[3-(aryl)hexahydro[1,3]oxazolo[3,4-a]pyridin-1-yl]-2,8-bis(trifluoromethyl)quinolines, derived from (R*, S*)-(±)-mefloquine and arenealdehydes, have been evaluated for their activity against four cancer cell lines (HCT-8, OVCAR-8, HL-60, and SF-295). Good cytotoxicities have been determined with IC50 values ranging from 0.59 to 4.79 μg/mL. In general compounds with aryl groups having strong electron-releasing substituents, such as HO and MeO, or electron-rich heteroaryl groups, for example imidazol-2-y-l, are active. However, other factors such as steric effects may play a role. As both the active and non-active conformations of the mefloquine-oxazolidine derivatives are similar, it is concluded that molecular conformations do not play a significant role either. This study is the first to evaluate mefloquine derivatives as antitumor agents. The mefloquine-oxazolidine derivatives are considered to be useful leads for the rational design of new antitumor agents.


Endothelial release of tissue-type plasminogen activator in the human forearm: role of nitric oxide.
Release of tissue-type plasminogen activator (t-PA) from the vascular endothelium is paramount to endogenous thrombolysis potential. In addition to its vasodilator effects, nitric oxide (NO) has important antithrombotic properties, such as inhibition of platelet aggregation. It is currently not clear whether NO influences the capacity of the endothelium to release t-PA. The authors determined whether net endothelial t-PA release is regulated, at least in part, by NO. Endothelial t-PA release was determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5-50.0 ng.100 mL tissue-1.min-1) in the presence and absence of the NO synthase inhibitor, NG-monomethyl-l-arginine (l-NMMA; 5 mg/min) in 12 healthy men. Net release of t-PA across the forearm vascular bed was calculated as the product of arteriovenous concentration gradient and forearm plasma flow. The vasodilator response to bradykinin was significantly blunted ( approximately 30%) with l-NMMA. Although there was no effect of l-NMMA on basal t-PA release, acute release of t-PA to bradykinin was higher (P < 0.01) after (from -0.2 +/- 0.5 to 105.2 +/- 9.4 ng.100 mL tissue-1.min-1) versus before (from -0.4 +/- 0.7 to 48.7 +/- 7.3 ng.100 mL tissue-1.min-1) the administration of l-NMMA. Thus, in the absence of NO endothelial t-PA release was enhanced. These results suggest a potential regulatory influence of NO on bradykinin induced endothelial t-PA release.


FABP4 activates the JAK2/STAT2 pathway via Rap1a in the homocysteine-induced macrophage inflammatory response in ApoE-/- mice atherosclerosis.
Atherosclerosis is a chronic inflammatory vascular disease, and inflammation plays a critical role in its formation and progression. Elevated serum homocysteine (Hcy) is an independent risk factor for atherosclerosis. Previous studies have shown that fatty acid binding protein 4 (FABP4) plays an important role in macrophage inflammation and lipid metabolism in atherosclerosis induced by Hcy. However, the underlying molecular mechanism of FABP4 in Hcy-induced macrophage inflammation remains unknown. In this study, we found that FABP4 activated the Janus kinase 2/signal transducer and activator of transcription 2 (JAK2/STAT2) pathway in macrophage inflammation induced by Hcy. Of note, we further observed that ras-related protein Rap-1a (Rap1a) induced the Tyr416 phosphorylation and membrane translocation of non-receptor tyrosine kinase (c-Src) to activate the JAK2/STAT2 pathway. In addition, the suppressor of cytokine signaling 1 (SOCS1)-a transcriptional target of signal transducer and activator of transcription (STATs) inhibited the JAK2/STAT2 pathway and Rap1a expression via a negative feedback loop. In summary, these results demonstrated that FABP4 promotes c-Src phosphorylation and membrane translocation via Rap1a to activate the JAK2/STAT2 pathway, contributing to Hcy-accelerated macrophage inflammation in ApoE-/- mice.


Comparison of phytolacain R, a cysteine protease from Phytolacca americana, with papain.
Nine sites of oxidized insulin B-chain were cleaved by phytolacain R, isolated from pokeweed, after 20 hr of hydrolysis. Five cleavage sites resembled those of papain. Substrate specificity of phytolacain R was similar to that of papain, preferring hydrophobic P2 residues. The activities of fibrin formation and elastin hydrolysis of phytolacain R were higher than those of papain. The amino terminal sequence of phytolacain R, although similar was not identical with that of papain.


Towards the tailored design of benzotriazinyl-based organic radicals displaying a spin transition.
The mechanism of the phase transition of 1-phenyl-3-trifluoromethyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl (1), the first reported triazinyl radical to present such a feature, is unveiled. In so doing, we identify the key ingredients that are crucial to enable the phase transition in this family of radicals, and how those can be exploited by a rational design of the spin-carrying units.


Co-expression of the small heat shock protein, Lo18, with β-glucosidase in Escherichia coli improves solubilization and reveals various associations with overproduced heterologous protein, GroEL/ES.
We developed a new system to improve the overproduction of soluble proteins in E. coli based on a plasmid encoding the small heat-shock protein, Lo18, derived from the lactic acid bacterium Oenococcus oeni. The efficiency of this system was compared with that of another system based on production of the E. coli universal chaperone GroEL/ES. A compatible plasmid encoding β-glucosidase was constructed for the overproduction and aggregation of this enzyme. Co-expression with Lo18 resulted in an increase in soluble β-glucosidase levels similar to that obtained in the GroEL/ES co-expression system. Lo18 was found preferentially in the insoluble fraction, associated with aggregated enzyme. By contrast, GroEL/ES was more abundant in the soluble fraction.


Flexural behavior of PEEK materials for dental application.
The high-performance thermoplastic polymer PEEK (poly-ether-ether-ketone) is used as alternative implant material to metals since 1998 in many medical fields due to its bone-like mechanical properties. These iso-elastic characteristics of PEEK lead to the assumption, that it could represent a viable alternative to conventional materials also in the field of dentistry. Therefore the mechanical properties of different PEEK-compounds should be eavuated vie the three-point bending test. 150 specimens of 11 different PEEK-compounds were tested via a three-point bending test using a universal testing machine (Z010, Zwick GmbH & Co, Ulm, Germany) after dry storage on the one hand and after incubation at 37°C in Ringer solution (Fa. Braun Melsungen AG, Melsungen, Deutschland) for one day, 7 days, 28 days und 84 days on the other hand and the material parameters bending modulus and bending strength were evaluated. The results regarding the bending moduli ranged from 2.73±0.26GPa for an unfilled brand to 47.27±10.3GPa for a carbon fiber reinforced PEEK with unidirectional continuous carbon fibers. Accordingly the bending strengths of these two material types ranged from 170.37±19.31MPa to 1009.63±107.33MPa. All tested specimens showed higher values than the prevailing minimum strength for plastic materials and their application in dentistry of 65MPa (DIN EN ISO 10477). This underlines the applicability of PEEK in dentistry and points out the possibility to offer patients metal free restorations, especially in the presence of allergies and/or bruxism.


Primary angioplasty for acute myocardial infarction in 1,000 consecutive patients. Results in an unselected population and high-risk subgroups.
Primary angioplasty (direct angioplasty without antecedent thrombolytic therapy) has remained an exclusive and consistent method of infarct intervention at our institution over the past 13 years. A total of 1,000 consecutive patients were prospectively enrolled in our primary angioplasty database. Of patients presenting to our group with an acute myocardial infarction, 96% of those eligible received immediate angioplasty. Cardiogenic shock was noted in 79 patients (7.9%). The mean time from pain onset to reperfusion was 5.4 +/- 4.0 hours. Infarct-vessel recanalization was accomplished in 94% of patients. Recanalization rates were similar among the 3 native epicardial coronary systems but were lower in bypass grafts (86%; p < 0.0001). Overall in-hospital mortality was 7.8%; mortality with cardiogenic shock was 44%. Global ejection fraction increased from 49.7% preangioplasty to 57.4% at the time of dismissal. The amount of myocardial salvage was highly dependent on the size of the initial infarction (the largest infarctions benefiting the most). Patients reperfused in < 2 hours experienced a very low mortality (4%) and impressive myocardial salvage. Complications included stroke in 0.5%, significant bleeding in 2.8%, and early reocclusion of the infarct vessel in 13%. Primary angioplasty is broadly applicable to patients presenting with acute myocardial infarction and results in a very high rate of infarct vessel recanalization, with a mortality rate of 7.8%. This strategy may be uniquely effective in patients presenting with cardiogenic shock, large infarctions, contraindications to thrombolytic therapy, and prior bypass surgery.


Combined Celiac Ganglia and Plexus Neurolysis Shortens Survival, Without Benefit, vs Plexus Neurolysis Alone.
Pancreatic cancer produces debilitating pain that opioids often ineffectively manage. The suboptimal efficacy of celiac plexus neurolysis (CPN) might result from brief contact of the injectate with celiac ganglia. We compared the effects of endoscopic ultrasound-guided celiac ganglia neurolysis (CGN) vs the effects of CPN on pain, quality of life (QOL), and survival. We performed a randomized, double-blind trial of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain; 60 patients (age 66.4±11.6 years; male 66%) received CPN and 50 patients (age 66.8±10.0 years; male 56%) received CGN. Primary outcomes included pain control and QOL at week 12 and survival (overall median and 12 months). Secondary outcomes included morphine response, performance status, secondary neurolytic effects, and adverse events. Rates of pain response at 12 weeks were 46.2% for CGN and 40.4% for CPN (P = .84). There was no significant difference in improvement of QOL between the techniques. The median survival time was significantly shorter for patients receiving CGN (5.59 months) compared to (10.46 months) (hazard ratio for CGN, 1.49; 95% CI, 1.02-2.19; P = .042), particularly for patients with non-metastatic disease (hazard ratio for CGN, 2.95; 95% CI, 1.61-5.45; P < .001). Rates of survival at 12 months were 42% for patients who underwent CPN vs 26% for patients who underwent CGN. The number of adverse events did not differ between techniques. In a prospective study of patients with unresectable pancreatic ductal adenocarcinoma and abdominal pain, we found CGN to reduce median survival time without improving pain, QOL, or adverse events, compared to CPN. The role of CGN must be therefore be reassessed. Clinicaltrials.gov no: NCT01615653.


Co-localization of RNAs coding for phenylethanolamine N-methyltransferase and proenkephalin A in bovine and ovine adrenals.
A 29-mer oligodeoxyribonucleotide probe, complementary to the coding region of bovine phenylethanolamine N-methyltransferase (PNMT) mRNA was synthesized. Characterization of this probe by Northern blot hybridization showed that it hybridized to a single band in RNA extracted from bovine and ovine adrenal medullae. The molecular size of this hybridized band was approximately 1.0-1.2 kb which is consistent with recently reported data on the molecular weight of bovine PNMT mRNA. In situ hybridization histochemistry was carried out with this probe on bovine and ovine adrenal sections and results compared on adjacent sections with a probe against proenkephalin A (ProEnk A) mRNA synthesized previously. Both showed a similar localization to the outer margin of cells in the adrenal medulla. The results of this study provide strong evidence at the level of mRNA expression that ProEnk A mRNA is expressed preferentially in the adrenaline synthesizing cells within the adrenal medulla. Further, it demonstrates the usefulness of a synthetic oligodeoxyribonucleotide probe for the study of PNMT gene expression.


Complete photocatalytic reduction of CO₂ to methane by H₂ under solar light irradiation.
Nickel supported on silica-alumina is an efficient and reusable photocatalyst for the reduction of CO2 to methane by H2, reaching selectivity above 95% at CO2 conversion over 90%. Although NiO behaves similarly, it undergoes a gradual deactivation upon reuse. About 26% of the photocatalytic activity of Ni/silica-alumina under solar light derives from the visible light photoresponse.


Ecological patterns, diversity and core taxa of microbial communities in groundwater-fed rapid gravity filters.
Here, we document microbial communities in rapid gravity filtration units, specifically serial rapid sand filters (RSFs), termed prefilters (PFs) and after- filters (AFs), fed with anoxic groundwaters low in organic carbon to prepare potable waters. A comprehensive 16S rRNA-based amplicon sequencing survey revealed a core RSF microbiome comprising few bacterial taxa (29-30 genera) dominated by Nitrospirae, Proteobacteria and Acidobacteria, with a strikingly high abundance (75-87±18%) across five examined waterworks in Denmark. Lineages within the Nitrospira genus consistently comprised the second most and most abundant fraction in PFs (27±23%) and AFs (45.2±23%), respectively, and were far more abundant than typical proteobacterial ammonium-oxidizing bacteria, suggesting a physiology beyond nitrite oxidation for Nitrospira. Within the core taxa, sequences closely related to types with ability to oxidize ammonium, nitrite, iron, manganese and methane as primary growth substrate were identified and dominated in both PFs (73.6±6%) and AFs (61.4±21%), suggesting their functional importance. Surprisingly, operational taxonomic unit richness correlated strongly and positively with sampling location in the drinking water treatment plant (from PFs to AFs), and a weaker negative correlation held for evenness. Significant spatial heterogeneity in microbial community composition was detected in both PFs and AFs, and was higher in the AFs. This is the first comprehensive documentation of microbial community diversity in RSFs treating oligotrophic groundwaters. We have identified patterns of local spatial heterogeneity and dispersal, documented surprising energy-diversity relationships, observed a large and diverse Nitrospira fraction and established a core RSF microbiome.


Risk factors for exposure of Baerveldt glaucoma drainage implants: a case-control study.
Glaucoma drainage implant exposure is one of the serious complications after glaucoma drainage implant surgery. The purpose of this study is to evaluate the risk factors for exposure of the device after implantation of a Baerveldt glaucoma drainage implant. This is a retrospective review of the medical records of all patients who underwent Baerveldt glaucoma drainage implant surgery at the Hiroshima University Hospital between April 1, 2012 and October 31, 2016, and who were followed for at least 6 months after surgery. We examined the risk factors for implant exposure based on data obtained from the medical records, with a particular focus on the differences in implant models. A total of 80 eyes from 80 patients were identified; all patients were Japanese. In this study, the rate of Baerveldt glaucoma drainage implant exposure was 15.0% (12 of 80 eyes). The exposure rate for the BG 102-350 tended to be higher than that for the BG 101-350 and BG 103-250 (p = 0.092; adjusted odds ratio = 3.34; 95% confidence interval, 0.82-13.58). In the patients who had diabetic mellitus, the BG 102-350 showed a significant risk of implant exposure (p = 0.038; adjusted odds ratio = 15.36; 95% confidence interval, 1.17-202.59). In Baerveldt glaucoma drainage implant surgery in patients with diabetes, using the BG 102-350 was associated with greater risk of implant exposure compared with using the BG 101-350 or BG 103-250.


Association of the 2021 Child Tax Credit Advance Payments With Low Birth Weight in the US.
Infants and pregnant people in the US fare worse on almost all health measures compared with those in peer nations. Families in the US are more likely to live in poverty and have a less generous social safety net, which has generated debate over the contribution of economic conditions to this disparity. To assess the association between temporary increases in income during pregnancy through the 2021 expanded Child Tax Credit (CTC) and birth outcomes. This cross-sectional study applied a comparison-population, interrupted time series design to data from US birth certificates (January 1, 2014, through December 31, 2021) to test whether the log odds of low birth weight (LBW) among monthly cohorts of births exposed to the CTC would coincide with a decreased incidence of LBW. All singleton live births to US residents aged 15 to 49 years with available data were included. Monthly birth cohorts exposed to the CTC were defined as those born to parous people during the CTC advance payment period from July through December 2021. The main outcome was the natural logarithm of the odds of LBW (<2500 g) among monthly birth cohorts. Among included births (n = 28 866 466), 61.2% were to parous people, the majority were to people aged 20 to 39 years (91.7%), and 6.5% were born LBW. The odds of LBW increased above expected values in 5 of the 6 months of the CTC payments (range of increases, 3.3%-5.4% across the 5 months). The outlier-adjusted odds of LBW increased, on average, by 4.2% (95% CI, 2.7%-5.7%) among the monthly birth cohorts exposed to the CTC. This study found that the odds of LBW among birth cohorts exposed to the CTC increased above expected values in 5 of the 6 months of the CTC advance payments. Additional research is needed to evaluate rival explanations for this increase in LBW among births exposed to the CTC payments.


Glutamate-induced inhibition of D-aspartate uptake in Müller glia from the retina.
Müller glial cells from the retina "in situ" and in primary culture, mainly express the high-affinity sodium-coupled glutamate/aspartate transporter GLAST-1, which dominates total retinal glutamate (Glu) uptake, suggesting a major role for these cells in the modulation of excitatory transmission. The possible involvement of ionotropic and metabotropic Glu receptors in the regulation of Glu uptake was studied in primary cultures of Müller glia. We demonstrate that exposure to 1 mM L-Glu induces a time-dependent inhibition of D-aspartate (D-Asp) uptake in a Na+-dependent manner, as a result of a reduction in the number of transporters at the plasma membrane. The inhibition of D-Asp uptake by Glu was not mimicked by agonists or modified by antagonists of ionotropic and metabotropic Glu receptors. In contrast, transport was inhibited by GLAST-1 transportable substrates threo-hydroxyaspartate and aspartate-beta-hydroxamate, but not by the nontransportable inhibitors trans-pyrrolidine dicarboxylate or DL-threo-beta-benzyloxyaspartic acid. Under the same experimental conditions, L-Glu did not affect the sodium-dependent transport systems for glycine or GABA. The present results demonstrate that the specific downregulation of glutamate/aspartate transport by L-Glu is unrelated to Glu receptor activation, and results from the internalization of transporter proteins triggered by the transport process itself. Such negative feedback of Glu on Glu transport, could contribute to retinal toxicity under pathological conditions in which high extracellular concentrations of Glu are reached.


Illness negotiation: the case of eating disorders.
This article explores the possible relationship between professional writing on eating disorders and the occurrence of symptoms. The clinical situation is seen as one in which negotiation about symptoms affects and is affected by both professional and popular explanatory models. Professional understanding is not necessarily categorically distinct from popular conceptions. Furthermore, it may be that different academic models hold different assumptions about normality and may expect different types of 'normal' behaviour from patients. Professional writing and educative material may be playing a function not dissimilar from material generally seen as exploitative in educating women into development of symptoms. This possibility has implications for the way that professional understanding is viewed and contextualized.


Inhibitory effects of acetylmelodorinol, chrysin and polycarpol from Mitrella kentii on prostaglandin E₂ and Thromboxane B₂ production and platelet activating factor receptor binding.
Acetylmelodorinol, chrysin and polycarpol, together with benzoic acid, benzoquinone and stigmasterol were isolated from the leaves of Mitrella kentii (Bl.) Miq. The compounds were evaluated for their ability to inhibit prostaglandin E₂ (PGE₂) and thromboxane B₂ (TXB₂) production in human whole blood using a radioimmunoassay technique. Their inhibitory effect on platelet activating factor (PAF) receptor binding to rabbit platelet was determined using ³H-PAF as a ligand. Among the compounds tested, chrysin showed a strong dose-dependent inhibitory activity on PGE(2) production (IC₅₀ value of 25.5 µM), which might be due to direct inhibition of cyclooxygenase-2 (COX-2) enzymatic activity. Polycarpol, acetylmelodorinol and stigmasterol exhibited significant and concentration-dependent inhibitory effects on TXB₂ production with IC₅₀ values of 15.6, 19.1 and 19.4 µM, respectively, suggesting that they strongly inhibited COX-1 activity. Polycarpol and acetylmelodorinol showed strong dose-dependent inhibitory effects on PAF receptor binding with IC₅₀ values of 24.3 and 24.5 µM, respectively.


Adult Fanconi syndrome secondary to kappa-light chain myeloma: improvement of tubular functions after treatment for myeloma.
A 66-year-old man with kappa-light chain multiple myeloma had adult Fanconi syndrome. Renal tubular transport abnormalities consisted of renal tubular acidosis, renal glycosuria, aminoaciduria, phosphaturia and renal hypouricemia. After therapy for multiple myeloma, urinary Bence Jones protein became undetectable, and all these renal tubular abnormalities except urate wasting were corrected. Histological examination revealed electron-dense tubular and rod-like deposits in proximal tubular epithelium. This clinical observation suggests that the renal tubular transport defects were secondary to the myeloma process, possibly due to Bence Jones proteinuria.


Candidemia in patients with head and neck cancer: mortality and a novel risk factor.
Candidemia is a bloodstream infection (BSI) by Candida spp. and is associated with high mortality. However, there have been few reports about BSI in head and neck cancer (HNC). We aimed to evaluate the impact of candidemia in patients with HNC and compared it with bacteremia. A multicenter retrospective study. We retrospectively analyzed 83 BSI episodes in HNC (2011 to 2020) and divided them into the candidemia and bacteremia groups. We then compared the survival rate and risk factors for candidemia between the groups. The overall cumulative incidence (risk) of candidemia in BSI was 12 out of 83 episodes (14.5%). The 1-year mortality for the bacteremia and candidemia groups was 33.3% and 58.3%, respectively (log-rank p = 0.041). Broad-spectrum antibiotics (odds ratio [OR]: 29.5; 95% confidence interval [CI], 2.49-350), mucositis (OR 11.0; 95% CI, 1.52-80.1), and malignant wounds (OR 79.5; 95% CI 1.33-4737) were significant risk factors for candidemia in HNC. Candidemia causes high mortality in patients with HNC. To our knowledge, malignant wounds have not been previously reported as a risk factor for candidemia. For early diagnosis and treatment of candidemia, risk factors should be considered, and antifungal therapy started earlier.


Evaluation of Bluetooth as a replacement for cables in intensive care and surgery.
In today's intensive care and surgery, a great number of cables are attached to patients. These cables can make the care and nursing of the patient difficult. Replacing them with wireless communications technology would facilitate patient care. Bluetooth is a modern radio technology developed specifically to replace cables between different pieces of communications equipment. In this study we sought to determine whether Bluetooth is a suitable replacement for cables in intensive care and during surgery with respect to electromagnetic compatibility. The following questions were addressed: Does Bluetooth interfere with medical equipment? And does the medical equipment decrease the quality of the Bluetooth communication? A Bluetooth link, simulating a patient monitoring system, was constructed with two laptops. The prototype was then used in laboratory and clinical tests according to American standards at the Karolinska Hospital in Stockholm. The tests, which included 44 different pieces of medical equipment, indicated that Bluetooth does not cause any interference. The tests also showed that the hospital environment does not affect the Bluetooth communication negatively. Bluetooth, a new radio technology transmitting at 2.4 GHz, was tested in a clinical setting. The study showed that a single Bluetooth link was robust and electromagnetically compatible with the tested electronic medical devices.


Assessment of sexual health in aging men in Europe: development and validation of the European Male Ageing Study sexual function questionnaire.
Assessment of male sexual dysfunction has been the focus of substantial scientific effort. Less research has focused on the development of instruments for the measurement of sexual functioning in aging men. The aims of this study were: (i) to characterize the psychometric properties of a new brief, reliable, and valid measure of male sexual functioning for use in a large population survey of middle-aged and elderly European men; and (ii) specifically, to determine whether the new instrument, the European Male Ageing Study-sexual function questionnaire (EMAS-SFQ), discriminates between men with high and low levels of circulating testosterone (T) (total T, free T, and bioavailable T). One thousand six hundred men aged 40-79 years completed the self-administered EMAS-SFQ, the Beck depression inventory, and provided a blood sample for assessment of sex hormones. Eighty-five men aged 35-74 years completed the EMAS-SFQ twice, 2 weeks apart to examine the test-retest reliability of the instrument. Scores on the EMAS-SFQ in relation to age and T levels. Principal component analysis showed that the EMAS-SFQ had four distinct domains (overall sexual functioning [OSF], masturbation, sexual functioning-related distress, and change in sexual functioning). The instrument demonstrated excellent internal and test-retest reliability, as well as convergent, divergent, and discriminant validity. Men with the lowest levels of total, free, and bioavailable T reported lower OSF scores compared to men with the highest T levels. The EMAS-SFQ is a valid and reproducible instrument, sensitive to age and T levels. It should be suitable for the assessment of sexual health in population samples of men in epidemiological studies of aging.


Cytokine induction by the immunomodulators imiquimod and S-27609.
Imiquimod (R-837, S-26308) and the analogue S-27609 were evaluated for cytokine induction in human blood cells. Both compounds induced interferon-alpha (IFN), tumor necrosis factor-alpha (TNF), interleukin (IL)-1 beta, and IL-6 with S-27609 being 5 to 10 times more potent. Imiquimod and S-27609 also induced IL-1 alpha, IL-1 receptor antagonist, IL-10, granulocyte-macrophage colony-stimulating factor (GM-CSF), granulocyte CSF (G-CSF), and macrophage inflammatory protein-1 alpha. The profile of cytokines induced by imiquimod and S-27609 was different from those seen with lipopolysaccharide and polyinosinic-polycytidylic acid. Kinetic studies with both imiquimod and S-27609 revealed induction of cytokines as early as 1-4 h after stimulation. Although most of the cytokines produced by S-27609 were secreted, significant concentrations of IL-1 alpha and IL-1 beta remained intracellular. Monocytes were largely responsible for the cytokines produced. Finally, S-27609-induced mRNA expression for TNF, IFN, and IL-8, and this induction did not require protein synthesis. Taken together, these studies extend previous findings by showing induction of additional cytokines and providing insight into the mechanism of cytokine induction by these molecules.


Endogenous opioid peptides suppress cytokine-mediated upregulation of HIV-1 expression in the chronically infected promonocyte clone U1.
Opioid peptides appear to have an immunomodulatory activity. Using the chronically HIV-1-infected promonocyte clone U1, we investigated the effect of endogenous and synthetic opioid agonists on cytokine-induced HIV-1 expression. None of the endogenous or synthetic opioid agonists had an effect on constitutive HIV-1 expression. Opioid agonists such as methionine-enkephalin, dynorphin, and the kappa receptor agonist, U50,488, dose-dependently suppressed (> 40%) interleukin (IL)-6-induced upregulation of HIV-1 expression. Interestingly, opioid receptor antagonists (mu, delta, and kappa types) also inhibited (> 60%) IL-6-induced upregulation of HIV-1 expression. All opioid agonists and antagonists tested only modestly suppressed (< 20%) tumor necrosis factor-alpha-induced upregulation of HIV-1 expression in U1 cell cultures. These data suggest that certain opioid peptides alter an IL-6-induced signal transduction pathway which triggers HIV-1 expression in the chronically infected promonocyte U1.


Comparison of salivary calcium level in smokers and non-smokers with chronic periodontitis, aggressive periodontitis, and healthy controls.
The purpose of this study was to compare salivary calcium (Ca) level in smokers and non-smokers with chronic periodontitis, aggressive periodontitis, and healthy controls. 56 subjects were included in the study and were grouped as follows: 12 subjects who were periodontally healthy (Group I), 12 subjects having chronic periodontitis who were non-smokers (Group II), 12 non-smokers having aggressive periodontitis (Group III), 12 smokers with chronic periodontitis (Group IV), and 8 smokers with aggressive periodontitis (Group V). Clinical measurements and non-stimulated whole saliva samples were obtained and analyzed for Ca levels by ion-selective electrolyte analyzer. When salivary Ca values were compared between the groups, they showed statistically significant values (P < 0.001) with the highest mean Ca level in Group IV and Group V, which include smokers with chronic periodontitis and smokers with aggressive periodontitis, respectively, than in other groups. Between groups II and III also, the mean salivary Ca level was statistically significant (P < 0.001) with higher mean salivary Ca in non-smokers having chronic periodontitis than in non-smokers having aggressive periodontitis. The present study showed that smokers having chronic periodontitis as well as smokers having aggressive periodontitis have higher salivary calcium levels. Also, patients with aggressive periodontitis were found to have lesser salivary calcium level than chronic periodontitis patients by ion-selective electrolyte analyzer.


Prostate cancer mortality and birth or adult residence in the southern United States.
Although there are few confirmed risk factors for prostate cancer (PCa), mortality rates are known to vary geographically across the United States. PCa mortality is higher among black and younger white men in a band of states spanning from Washington DC to Louisiana (the "PCa belt"). This study assessed the associations of birth and adult residence in the PCa belt with PCa mortality among black and white men and trends in these associations over time. PCa-specific mortality rates in 1980, 1990, and 2000 for black and white men born in the continental US, aged 40-89, were calculated by linking national mortality records with population data based on birth state, state of residence at the census, race, and age. PCa belt (Washington DC, Virginia, North Carolina, South Carolina, Georgia, Mississippi, Alabama, and Louisiana) birth was cross-classified against PCa belt adult residence. Black men born in the PCa belt had elevated PCa mortality in 1980, 1990, and 2000. Associations were independent of adult residence in the PCa belt. For example, in 2000, black men aged 65-89 who were born in the PCa belt but no longer lived there in adulthood had an odds ratio of 1.19 (1.14-1.24) for PCa mortality compared to black men born and residing outside the PCa belt. The PCa belt was not associated with PCa mortality among whites. Geographically patterned childhood exposures, for example, differences in social or environmental conditions, or behavioral norms, may influence PCa mortality.


Bone density of élite female athletes with stress fractures.
To investigate whether stress fractures occurring in élite female athletes are related to reductions in bone mineral density (BMD), we measured BMD in nine athletes with such fractures and nine athletes without fractures who were matched for age, weight, height and sport. BMD was measured in three regions: upper limbs (distal radius), axial skeleton (lumbar spine) and lower limbs (femoral neck) by photon absorptiometry. The number of menses per year was significantly less (P less than 0.04) and the age of menarche was significantly delayed (mean +/- SD; 16.1 +/- 0.4 v. 14.4 +/- 1.5 years, P less than 0.02) in the fracture group compared with the non-fracture group. There was no significant difference in BMD between the two groups at any of the measurement sites. Moreover although the fractures occurred mainly in lower limb bones, at sites characterised by predominantly cortical bone, all athletes had femoral neck BMD values within the 95% confidence limits for normal non-athletic women. We conclude that stress fractures in élite female athletes are largely independent of BMD.


Nb rat prostate adenocarcinoma model androgen-sensitive tumor: metastasis control.
In this preliminary report, evaluation of nontraditional agents has been used to evaluate control of metastasis. This androgen-sensitive rate prostatic adenocarcinoma has been subject to the treatments of heparin, indocin, and castration, as well as combinations of castration, heparin, indocin, and cyclophosphamide. Tumor volume, metastasis, and determination of regression of primary tumor have been evaluated. Heparin and indocin both reduced metastasis without affecting tumor volume in this study. The combination of castration and cyclophosphamide was most effective in reducing tumor volume when compared to the other groups.


ATP-dependent degradation of 3-hydroxy-3-methylglutaryl coenzyme A reductase in permeabilized cells.
A system for the assay of 3-hydroxy-3-methyglutaryl (HMG) coenzyme A (CoA) reductase in digitonin-permeabilized Chinese hamster ovary cells is described. Under these conditions, HMG-CoA reductase remained intact and associated with the endoplasmic reticulum, and values for Km (HMG-CoA), Ki (mevinolin), and active/total activity were similar to those seen in sonicated cell preparations. However, the mechanism by which this rapidly turned over (half-life approximately 2 h) enzyme is degraded was disrupted. Addition of ATP at physiological concentrations to digitonin-permeabilized cells resulted in the rapid, irreversible loss of enzyme activity. Immunoblot analysis showed that this loss of activity was followed by cleavage of the intact 97-kilodalton enzyme to a 68-kilodalton fragment which was distinct from the catalytically active fragments generated by nonspecific proteolysis in sonicated cell homogenates. Assay of a lysosomal marker enzyme confirmed that ATP-mediated inactivation and cleavage of reductase was not due to release of lysosomal proteases. The possible role of ATP in phosphorylation, inactivation, and degradation of reductase is discussed.


The 5q-anomaly.
A deletion of the long arm of chromosome #5 (5q-) occurs nonrandomly in human malignancies. As a rule, the deletion is interstitial; the distal breakpoint by conventional techniques is usually in band q32, the proximal breakpoints in q12 or q14. Variant breakpoints occur in less than 10% of all cases. As the sole anomaly, 5q- is characteristically found in refractory anemia with or without excess of blasts. It can occur as the sole anomaly in de novo or secondary acute nonlymphocytic leukemia, but is usually accompanied in those disorders by other chromosome changes that are also nonrandomly distributed. In addition, it can be found in lymphoproliferative disorders, and occasionally, also in solid tumors. The 5q- myelodysplastic syndrome typically occurs in older age groups, particularly in females. Characteristic features are macrocytic anemia, normal or elevated platelets in the presence of megakaryocytic anomalies, and a mild clinical course. In cases with 5q- only, transformation into ANLL occurs rarely. Additional chromosome anomalies and male sex are prognostically unfavorable signs. Sex ratio is also at the disadvantage of females in de novo 5q- ANLL, and the latter disorder can occur without being preceded by a myelodysplastic phase. A myelodysplastic phase usually precedes 5q- secondary leukemia, in males as well as in females, and additional chromosome anomalies, especially of chromosome #7, are almost invariably present in those cases. We conclude that 5q- is the most frequently occurring single chromosome anomaly in secondary leukemia. Furthermore, the resemblance between de novo and secondary 5q- MDS and ANLL is striking; clinically, as well as cytogenetically, they are indistinguishable, suggesting that all de novo cases may be due to environmental (chemical) carcinogens. Response to treatment and prognosis are very poor with current therapeutic regimens in de novo as well as in secondary 5q- ANLL. Morphologically, these ANLLs fall into all FAB categories. There is considerable evidence to show that the 5q- anomaly occurs in a myeloid precursor stem cell. The occasional occurrence in lymphoid malignancies, of B cell as well as T cell type, suggests that, as in Ph-positive disorders, a common progenitor stem cell may be affected in 5q- also. The 5q- lymphoid malignancies, however, are much more rare; it is not clear at the present time whether or not a 5q- counterpart of Ph-positive ALL exists, and mixed lymphoid-myeloid 5q- disorders have not yet been documented.(ABSTRACT TRUNCATED AT 400 WORDS)


The use of hormonal therapy with radiotherapy for prostate cancer: analysis of prospective randomised trials.
In 1901, Wilhelm Conrad Röntgen won the Nobel prize in Physics for his discovery of the Röntgen rays or, as he himself called them, X-rays. In 1966, Dr Charles Brenton Higgins won the Nobel Prize in Medicine for his breakthroughs concerning hormonal treatment of prostatic cancer. After 31 years, in 1997, the first prospective randomised trials of the combination of hormonal therapy and radiation therapy were published, showing increased survival when compared to radiation therapy alone for patients with prostate cancer. Since 1997, many investigators have published trials combining hormonal and radiation therapy for prostate cancer. This minireview will address the largest and most influential of these trials, and attempt to guide physicians in selecting the appropriate patients for this combined approach.


Diagnosing perforated appendicitis in pediatric patients: a new model.
Studies have investigated sensitivity and specificity of symptoms and tests for diagnosing appendicitis in children. Less is known with regard to the predictive value of these symptoms and tests with respect to the severity of appendicitis. The aim of this study was to determine the predictive value of patient's characteristics and tests for discriminating between perforated and nonperforated appendicitis in children. Pediatric patients who underwent an appendectomy at Spaarne Hospital Hoofddorp, the Netherlands, between January 1, 2009 and December 31, 2013, were included. Baseline patient's characteristics, history, physical examination, laboratory data and results of ultrasounds were collected. Univariate and multivariate logistic regressions were used to determine predictors of perforation. In total, 375 patients were included in this study of which 97 children (25.9%) had significant signs of perforation. Univariate analysis showed that age, duration of complaints, temperature, vomiting, CRP, WBC, different findings on ultrasound and the diameter of the appendix were good predictors of a perforated appendicitis. The final multivariate prediction model included temperature, CRP, clearly visible appendix and free fluids on ultrasound and diameter of the appendix and resulted in an area under the curve (AUC) of 0.91 showing sensitivity and specificity of respectively 85.2% and 81.2%. This prediction model can be used for identification of 'high-risk' children for a perforated appendicitis and might be helpful to prevent complications and longer hospitalization by bringing these children to theater earlier.


Chromium (VI) and zinc (II) waste water co-treatment by forming layered double hydroxides: mechanism discussion via two different processes and application in real plating water.
Two processes, adsorption after synthesis (AAS) and adsorption during synthesis (ADS) were compared in CrO4(2-) and Zn2+/CrO4(2-) removal. Kinetic results showed that ADS was a better method than AAS, since Cr content was 0.65/0.81 mmol/g in Cr-ADS/ZnCr-ADS, but it was only 0.37/0.56 mmol/g in Cr-AAS/ZnCr-AAS. Then, a low-cost mixture was proposed to function as ADS raw materials in treating real plating waters. This mixture first got an isothermal saturation of 1.1 mmol/g in simulated CrO4(2-) water. When Zn2+ was co-treated, it was increased to 1.3 mmol/g. At the same time, a Zn2+ removal of 1.5 mmol/g was attained. Furthermore, real plating water co-treatment reached equilibrium in 6h and obtained 1.4/0.9 mmol/g for Zn2+/CrO4(2-), respectively. According to XRD analysis, this co-treatment enhancement resulted from the formation of Zn and Cr contained layered double hydroxide.


Hepatoprotective Effects of Aureobasidium pullulans Derived β 1,3-1,6 Glucans in a Murine Model of Non-alcoholic Steatohepatitis.
Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are highly prevalent conditions characterized by inflammation and fibrosis of the liver, which can progress to cirrhosis and hepatocellular carcinoma if left untreated. Conventional modalities are mainly symptomatic, with no definite solution. Beta-glucan-based biological response modifiers are a potential strategy in lieu of their beneficial metabolic effects. Aureobasidium pullulans strains AFO-202 and N-163 beta-glucans were evaluated for anti-fibrotic and anti-inflammatory hepatoprotective potentials in a NASH animal model in this study. In the STAM™ murine model of NASH, five groups were studied for 8 weeks: (1) vehicle (RO water), (2) AFO-202 beta-glucan; (3) N-163 beta-glucan, (4) AFO-202+N-163 beta-glucan, and (5) telmisartan (standard pharmacological intervention). Evaluation of biochemical parameters in plasma and hepatic histology including Sirius red staining and F4/80 immunostaining were performed. AFO-202 beta-glucan significantly decreased inflammation-associated hepatic cell ballooning and steatosis. N-163 beta-glucan decreased fibrosis and inflammation significantly (P value < 0.05). The combination of AFO-202 with N-163 significantly decreased the NAFLD Activity Score (NAS) compared with other groups. This preclinical study supports the potential of N-163 and AFO-202 beta-glucans alone or in combination as potential preventive and therapeutic agent(s), for NASH.


Cyclic AMP increases endogenous granulocyte colony-stimulating factor formation in monocytes and THP-1 macrophages despite attenuated TNF-alpha formation.
The cytokine granulocyte colony-stimulating factor (G-CSF) is in broad clinical use to treat neutropenia, and trials on its use in immunosuppressed conditions and infections are ongoing. To apply G-CSF effectively, it is crucial to understand the regulation and distribution of its endogenous formation. Since G-CSF release is mediated, at least in part, by TNF-alpha formation, we investigated whether drugs suppressing TNF-alpha also impair G-CSF production. Surprisingly, G-CSF formation was enhanced in lipopolysaccharide (LPS)-stimulated blood from a pentoxifylline-treated patient. In the presence of dibutyryl-cAMP, forskolin, tolafentrine or 3-isobutyl-1-methylxanthine, LPS-induced G-CSF formation was enhanced in THP-1 cells, primary monocytes and whole blood. Correspondingly,rp-8-bromo-cAMP suppressed LPS-induced G-CSF release. Addition of prostaglandin E(2) enhanced and indomethacin suppressed G-CSF formation. Reporter gene studies showed that dibutyryl-cAMP enhanced LPS-induced G-CSF promoter activity, indicating a transcriptional up-regulation. Furthermore, disruption of a newly identified putative cAMP-responsive element (CRE) in the G-CSF promoter demonstrated the regulatory role for G-CSF gene transcription. In conclusion, endogenous G-CSF formation critically depends on both TNF-alpha and cyclooxygenase products, exerting effects via cAMP and the CRE in the G-CSF promoter. This might have bearing for drug side effects, putative G-CSF mimetics and our understanding of G-CSF immunobiology.


Mining real-world high dimensional structured data in medicine and its use in decision support. Some different perspectives on unknowns, interdependency, and distinguishability.
There are many difficulties in extracting and using knowledge for medical analytic and predictive purposes from Real-World Data, even when the data is already well structured in the manner of a large spreadsheet. Preparative curation and standardization or "normalization" of such data involves a variety of chores but underlying them is an interrelated set of fundamental problems that can in part be dealt with automatically during the datamining and inference processes. These fundamental problems are reviewed here and illustrated and investigated with examples. They concern the treatment of unknowns, the need to avoid independency assumptions, and the appearance of entries that may not be fully distinguished from each other. Unknowns include errors detected as implausible (e.g., out of range) values that are subsequently converted to unknowns. These problems are further impacted by high dimensionality and problems of sparse data that inevitably arise from high-dimensional datamining even if the data is extensive. All these considerations are different aspects of incomplete information, though they also relate to problems that arise if care is not taken to avoid or ameliorate consequences of including the same information twice or more, or if misleading or inconsistent information is combined. This paper addresses these aspects from a slightly different perspective using the Q-UEL language and inference methods based on it by borrowing some ideas from the mathematics of quantum mechanics and information theory. It takes the view that detection and correction of probabilistic elements of knowledge subsequently used in inference need only involve testing and correction so that they satisfy certain extended notions of coherence between probabilities. This is by no means the only possible view, and it is explored here and later compared with a related notion of consistency.


Unveiling a hotspot of genetic diversity in southern Italy for the endangered Hermann's tortoise Testudo hermanni.
Hotspots of intraspecific genetic diversity represent invaluable resources for species to cope with environmental changes, and their identification is increasingly recognized as a major goal of conservation ecology research. However, even for iconic and endangered species, conservation strategies are often planned without thorough information on the geographic patterns of genetic variation. Here, we investigated the spatial patterns of genetic variation of the endangered Hermann's tortoise Testudo hermanni in the Italian Peninsula by genotyping 174 individuals at 7 microsatellite loci, with the aim to contribute to planning effective conservation strategies. Ordination-based and Bayesian clustering analyses consistently identified three main genetic clusters, one spread in the central and northern part of the peninsula, and two restricted to southern Italy and Sicily, respectively. The highest levels of genetic diversity were found in populations of the southern cluster and, in particular, at the northern edges of its distribution (He > 0.6, Ar > 2.8 ), that correspond to areas of putative secondary contact and admixture between distinct lineages. Our results clearly identify a hotspot of genetic diversity for the Hermann's tortoise in southern Italy. We inferred the evolutionary history and the spatial patterns of genetic variation of the Hermann's tortoise in the Italian Peninsula. We identified three main genetic clusters along the peninsula and a hotspot of intraspecific diversity in southern Italy. Our results underline the urgent need for conservation actions to warrant the long-term persistence of viable tortoise populations in this area. Furthrmore, these data add further evidence to the role of southern Italy as a biodiversity hotspot for temperate fauna, claiming for higher consideration of this area in large scale conservation programs.


Live birth rate is significantly higher after blastocyst transfer than after cleavage-stage embryo transfer when at least four embryos are available on day 3 of embryo culture. A randomized prospective study.
In a randomized controlled trial, we assessed whether pregnancy outcome would be improved by extending embryo culture to day 5 and transferring a blastocyst in patients with at least four good-quality embryos on day 3. Multifollicular ovarian stimulation was performed with a GnRH agonist in 44% of patients and with a GnRH antagonist in 56%. Overall, 164 patients younger than 37 years fulfilled embryo quality criteria (at least four having at least six cells on the morning of day 3, maximum 20% anucleate fragments) on the third day of culture and were randomized to the day 3 (n = 84) or day 5 (n = 80) groups. Equal numbers of embryos (n = 2) were transferred in each group. Demographics, stimulation parameters and embryological data were comparable in the two groups. Blastocyst-stage transfer resulted in a significantly higher ongoing pregnancy rate [51.3 versus 27.4%; odds ratio (OR) 2.78, 95% confidence interval (CI) 1.45-5.34] and live birth rate (47.5 versus 27.4%; OR 2.40, 95% CI 1.25-4.59) compared with day-3 embryo transfer. A high twin birth rate was observed in both groups (36.8 versus 30.4%; P > 0.05). A threshold of four good embryos on the third day of embryo culture appears to indicate that the patient will benefit from embryo transfer at the blastocyst stage and have a better chance of achieving a live delivery than with cleavage-stage embryo transfer.


Afraid and Awake: The Interaction Between Trauma and Sleep in Children and Adolescents.
Traumatic experiences and sleep disturbances are both common in children and adolescents. Because of the reciprocal relationship between sleep complaints and trauma, a mental health evaluation should include not only an assessment of posttraumatic stress disorder and other trauma symptoms but also a specific evaluation of sleep-related complaints. Similarly, if a history of both trauma and sleep complaints is identified, an effective trauma-informed intervention, whether psychological, psychopharmacologic, or a combination of the two, should directly address sleep issues.


Photoperiod and aggression induce changes in ventral gland compounds exclusively in male Siberian hamsters.
Chemical communication is a critical component of social behavior as it facilitates social encounters, allows for evaluation of the social partner, defines territories and resources, and advertises information such as sex and physiological state of an animal. Odors provide a key source of information about the social environment to rodents; however, studies identifying chemical compounds have thus far focused primarily on few species, particularly the house mouse. Moreover, considerably less attention has been focused on how environmental factors, reproductive phenotype, and behavioral context alter these compounds outside of reproduction. We examined the effects of photoperiod, sex, and social context on chemical communication in the seasonally breeding Siberian hamster. We sampled ventral gland secretions in both male and female hamsters before and after an aggressive encounter and identified changes in a range of volatile compounds. Next, we investigated how photoperiod, reproductive phenotype, and aggression altered ventral gland volatile compound composition across the sexes. Males exhibited a more diverse chemical composition, more sex-specific volatiles, and showed higher levels of excretion compared to females. Individual volatiles were also differentially excreted across photoperiod and reproductive phenotype, as well as differentially altered in response to an aggressive encounter. Female volatile compound composition, in contrast, did not differ across photoperiods or in response to aggression. Collectively, these data contribute to a greater understanding of context-dependent changes in chemical communication in a seasonally breeding rodent.


Rocky Planet Rotation, Thermal Tide Resonances, and the Influence of Biological Activity.
It has been established theoretically that atmospheric thermal tides on rocky planets can lead to significant modifications of rotational evolution, both close to synchronous rotation and at faster rotations if certain resonant conditions are met. Here it is demonstrated that the normally considered dissipative gravitational tidal evolution of rocky planet rotation could, in principle, be "stalled" by thermal tide resonances for Earth-analog worlds in the liquid-water orbital zone of stars more massive than [Formula: see text]. The possibility of feedback effects between a planetary biosphere and the planetary rotational evolution is examined. Building on earlier studies, it is suggested that atmospheric oxygenation and ozone production could play a key role in planetary rotational evolution, and therefore represents a surprising but potent form of biological imprint on astronomically accessible planetary characteristics.


Sleep spindles and human cortical nociception: a surface and intracerebral electrophysiological study.
Sleep spindle are usually considered to play a major role in inhibiting sensory inputs. Using nociceptive stimuli in humans, we tested the effect of spindles on behavioural, autonomic and cortical responses in two experiments using surface and intracerebral electroencephalographic recordings. We found that sleep spindles do not prevent arousal reactions to nociceptive stimuli and that autonomic reactivity to nociceptive inputs is not modulated by spindle activity. Moreover, neither the surface sensory, nor the insular evoked responses were modulated by the spindle, as detected at the surface or within the thalamus. The present study comprises the first investigation of the effect of spindles on nociceptive information processing and the results obtained challenge the classical inhibitory effect of spindles. Responsiveness to environmental stimuli declines during sleep, and sleep spindles are often considered to play a major role in inhibiting sensory inputs. In the present study, we tested the effect of spindles on behavioural, autonomic and cortical responses to pain, in two experiments assessing surface and intracerebral responses to thermo-nociceptive laser stimuli during the all-night N2 sleep stage. The percentage of arousals remained unchanged as a result of the presence of spindles. Neither cortical nociceptive responses, nor autonomic cardiovascular reactivity were depressed when elicited within a spindle. These results could be replicated in human intracerebral recordings, where sleep spindle activity in the posterior thalamus failed to depress the thalamocortical nociceptive transmission, as measured by sensory responses within the posterior insula. Hence, the assumed inhibitory effect of spindles on sensory inputs may not apply to the nociceptive system, possibly as a result of the specificity of spinothalamic pathways and the crucial role of nociceptive information for homeostasis. Intriguingly, a late scalp response commonly considered to reflect high-order stimulus processing (the 'P3' potential) was significantly enhanced during spindling, suggesting a possible spindle-driven facilitation, rather than attenuation, of cortical nociception.


On the reduction of eye-strain when reading.
Successive lines of printed text form a pattern of stripes that may induce eye-strain and headache. Volunteers suffering eye-strain or headache from reading were asked to use a variety of aids, some of which merely guided the eye and some of which also attenuated the pattern of stripes above and below the passage of text being read. In two studies about one-third of the volunteers benefited from the latter acids to the extent that they wished to continue using them despite the inconvenience involved. These volunteers tended to report more visual illusions when they looked at a pattern of striped lines.


Enhancement of carbon tetrachloride-induced liver injury by glucagon and insulin treatment.
Rats given a dose of carbon tetrachloride (CCl4) immediately received injections of glucagon and insulin every 4 h. They frequently died after 4 h and showed a significantly higher mortality between 8 h and 28 h as compared to the control rats where such deaths occurred 16 h later. At 8 h, the derangements of SGPT values and prothrombin time were significantly greater in the hormone-treated rats than in the control rats. In these CCl4-intoxicated rats, hepatic reduced glutathione content at 4 h was significantly reduced after hormone treatment. The treatment significantly enhanced CCl4 metabolism, conversion of 14CCl4 into 14CO2 in vitro, by microsomes isolated from the liver, whereas it did not affect the microsomal cytochrome P450 content. These results suggest that glucagon and insulin treatment increased CCl4 hepatotoxicity in rats through activating the cytochrome P450-dependent mono-oxygenase system. This would merit consideration for the clinical application of this treatment.


The anti-platelet actions of FR122047, a novel cyclooxygenase inhibitor.
The anti-platelet actions of 1-[(4,5-bis(4-methoxyphenyl)-2- thiazoyl)carbonyl]-4-methylpiperazine hydrochloride (FR122047) were investigated in vitro and in vivo. FR122047 was 100 times more potent than aspirin against arachidonic acid- and collagen-induced human and guinea-pig platelet aggregation in vitro. Its actions on platelets were a result of cyclooxygenase inhibition. The single oral dose of FR122047 inhibited arachidonic acid- and collagen-induced aggregation with an ED50 of 280 micrograms/kg and 530 micrograms/kg, respectively, in guinea-pigs. The anti-platelet action was augmented 5-10 times by repeated administration for 4 days. At 1 mg/kg the inhibitory actions were prolonged for 48 h and the drug concentration was < 0.1 ng/ml in platelet-poor plasma at 24 h and 0.282 ng/ml in platelet-rich plasma at 48 h. The safety margin in rats (minimum ulcerogenic dose/ED50 for anti-platelet aggregation) of FR122047 was more than 70, while that of aspirin was only 1.2. These results indicate that FR122047 is concentrated in platelets and may be a useful anti-platelet agent.


Hemodialysis without anticoagulation.
Heparin is usually employed as an anticoagulant during routine hemodialysis. In patients at high risk of bleeding, however, use of heparin significantly increases their morbidity and, presumably, mortality. Over 1 year, we performed 156 hemodialysis procedures successfully without heparin in the transplant dialysis unit. Twenty-eight patients were included in the study; 23 patients had received renal transplants and five patients were in the mouth dental extraction, and parathyroidectomy). Only one of these patients had a coagulopathy. No dialysis procedure produced or aggravated bleeding. Conversely, a coagulopathy was not induced or worsened by dialysis without heparin. A significant complication, defined as complete clotting of the artificial kidney with or without clotting in the lines, occurred in eight dialyses (5.13% of the total) and resulted in an average blood loss of 150 ml. Partial clotting of the dialyzer did not interrupt the procedure and occurred nine times (5.8% of the total). These results compare favorably with previously documented complications from low-dose and regional heparin.


Evidence on improved outcomes with early diagnosis of cystic fibrosis through neonatal screening: enough is enough!
To generate and examine evidence in support of diagnosing cystic fibrosis (CF) early through newborn screening (NBS). Using a randomized controlled trial with unique unblinding/surveillance, we evaluated patients with CF receiving similar treatment after assignment to an early diagnosis (screened) group or to a control group. Outcomes studied at diagnosis and longitudinally included measures of nutritional status and lung disease. Assessment of patients with CF without meconium ileus who had pancreatic insufficiency revealed marked differences in age and condition at diagnosis--screened patients had significantly better length/height, weight, and head circumference. Follow-up evaluation for 16 years showed that height and weight differences persisted long term. Although screened patients had better chest x-ray scores at diagnosis, our trial suggests that the effects of confounders such as Pseudomonas aeruginosa infections led to deterioration of their scores after 10 years, but there were no significant differences between the 2 CF/pancreatic insufficiency subgroups. Early diagnosis of CF and aggressive nutritional management can prevent malnutrition and growth failure. Although CF NBS provides a potential opportunity for better pulmonary outcomes, it appears that other factors can predominate over time in pulmonary prognosis. Overall, the Wisconsin trial is positive and provides enough evidence for routine CF NBS.


Visuomotor Prediction Errors Modulate EEG Activity Over Parietal Cortex.
The parietal cortex is thought to be involved in visuomotor adaptation, yet it remains unclear whether it is specifically modulated by visuomotor prediction errors (i.e. PEs; mismatch between the predicted and actual visual consequences of the movement). One reason for this is that PEs tend to be associated with task errors, as well as changes in motor output and visual input, making them difficult to isolate. Here this issue is addressed using electroencephalography. A strategy (STR) condition, in which participants were instructed on how to counter a 45° visuomotor rotation, was compared to a condition in which participants had adapted to the rotation (POST). Both conditions were matched for task errors and movement kinematics, with the only difference being the presence of PEs in STR. Results revealed strong parietal modulations in current source density and low theta (2-4 Hz) power shortly after movement onset in STR vs. POST, followed by increased alpha/low beta (8-18 Hz) power during much of the post-movement period. Given recent evidence showing that feedforward and feedback information is respectively carried by theta and alpha/beta oscillations, the observed power modulations may reflect the bottom-up propagation of PEs and the top-down revision of predictions.


Association between postoperative exposure to fine particulate matter and patency of the right ventricle-pulmonary artery conduit.
Ambient air pollution is a leading risk factor for cardiovascular diseases. No study has investigated the association between exposure to fine particulate matter <2.5 μm in aerodynamic diameter (PM2.5) and the prognosis of patients undergoing surgery for the right ventricle-pulmonary artery (RV-PA) conduit. From 2013 to 2020, patients with six complicated congenital heart defects who had undergone surgery for the RV-PA conduit were selected. Four conduit materials were used: bovine jugular vein graft (BJV), pulmonary homograft (PHG), aortic homograft (AHG), and handmade tri-leaflet expanded polytetrafluoroethylene (ePTFE) conduit. Telephone interviews were used to confirm the postoperative address of patients. The monthly average PM2.5 concentration was obtained from the ChinaHighPM2.5 dataset using the place of residence of patients. By comparing findings of echocardiography undertaken before patients' return to their residence and during re-examination, we defined an increase in the trans-conduit peak velocity of ≥1.5 m/s as the study endpoint. We enrolled 232 patients. Compared with BJV conduits, homografts (AHGs and PHGs) (0.052 (95 % CI = 0.005-0.558), P = 0.015) and ePTFE conduits (0.009 (95 % CI = 0.002-0.054), P < 0.001) were protective factors. The cumulative monthly PM2.5 concentration (10 μg/m3) was a risk factor (1.014 (95 % CI = 1.001-1.026), P = 0.028). Winter experience was a risk factor (1.971 (95 % CI: 1.021-3.804), P = 0.043). In the subgroup analysis, Spearman correlation analysis indicated BJV conduits (r = 0.680, P < 0.001), PHGs (r = 0.559, P = 0.020), and AHGs (r = 0.745, P = 0.021) had medium-to-high positive correlations between the cumulative PM2.5 concentration and change in the conduit velocity. For ePTFE, the correlation was weak and not significant (r = 0.222, P = 0.073). Postoperative exposure to PM2.5 affects the patency of biologic prosthetic conduits (especially xenografts). The increase in the velocity of the ePTFE conduit is not associated with PM2.5 exposure, and is a suitable material for patients living in areas with high pollutant concentrations.


Two populations of women with high and low spleen rates living in the same area of Madang, Papua New Guinea, demonstrate different immune responses to malaria.
Specific malaria and total IgM antibody responses were measured in 2 linguistically distinct coastal Papua New Guinean populations living in the same endemic malarious area, but exhibiting different adult female spleen rates (51% and 30%), in order to establish whether the higher spleen rates in the former group were due to hyper-reactive malarious splenomegaly (HMS). Malaria parasite rates were comparable, and geometric mean titres of IgG malaria antibody were the same, in both groups, indicating comparable exposure to malaria. A higher mean total IgM was observed in the high spleen (HS) rate group (6.07 g/litre, compared with 4.62 g/litre), a higher proportion was seropositive for IgM antibody to Plasmodium falciparum (63% compared with 54%), and HMS was found rather more frequently (4.7% compared with 2.6%). In both groups total IgM concentrations increased significantly with rising parity, and the mean level of 5.27 g/litre in young nulliparous women from the HS group suggested that IgM levels in this group at least were elevated from childhood. In both groups a rise in total IgM was associated with higher P. falciparum IgM geometric mean titres of antibody activity, a fall in parasite rates (HS group: 30% to 15%, P = 0.02; LS group: 24% to 0%, P = 0.034), and higher spleen rates (HS group: 38% to 65%, P = 0.001; LS group: 20% to 67%, P = 0.00012). It is concluded that the difference in spleen rates between the 2 groups was the result of differing degrees of acquired immunity to malaria, probably due to genetic differences in immune responses.(ABSTRACT TRUNCATED AT 250 WORDS)


The CathCam: A Novel Angioscopic Solution for Endovascular Interventions.
Peripheral arterial diseases are commonly managed with endovascular procedures, which often face limitations in device control and visualization under X-ray fluoroscopy guidance. In response, we developed the CathCam, an angioscope integrated into an expandable cable-driven parallel mechanism to enhance real-time visualization, precise device positioning and catheter support for successful plaque crossing. The primary objective of this study was to assess and compare the performance of the novel CathCam with respect to conventional catheters and the CathPilot (i.e., CathCam without the angioscope), for applications in crossing chronic total occlusions (CTO). We first assessed the system in 3D-printed phantom models, followed by an ex vivo evaluation with CTO samples from a patient's superficial femoral artery. We measured and compared success rates, crossing times, and fluoroscopy times in both experiments. The CathCam demonstrated a 100% success rate in phantom experiments and a 75% success rate in ex vivo experiments with CTO samples, compared to conventional catheters, with 35% and 25% success rates, respectively. The average crossing times for the CathCam and the conventional catheter were 31 s and 502 s for the phantom experiments and 210 s and 511 s for the actual CTO lesions. The Cathcam also showed to be a reliable endovascular imaging approach in an in vivo experiment. Compared to conventional catheters, the CathCam significantly increased the success rate and reduced crossing and fluoroscopy times in both phantom and ex vivo setups. CathCam can potentially improve clinical outcomes for minimally invasive endovascular interventions by offering high-resolution real-time imaging alongside accurate device control.


Animal cells in culture are microorganisms.
Pick up any textbook with 'Microbiology' in the title and observe the scant to nonexistent treatment of animal cells in culture. Viruses do not suffer from such an exclusion. Chapters abound regaling the molecular niceties of the complex dances their components undergo while infecting bacteria or animal cells in culture. Indeed, it is normally in the latter sense only that any recognition is given to the existence of animal cells in culture. Such views pervade even the minds of those who initiate and direct activities of societies whoseraison d'être is the growth and exploitation of animal cells in culture. The author of this editorial was appointed to a Chair in Microbiology at the University of Surrey in 1983 and has worked on the growth and use of animal cells in culture continuously since 1970; he, therefore, had to reconcile his position in the university with his chosen calling. In this he was helped by undergraduates too numerous to mention who struggled mightily with essays which asked the question; are animal cells in culture microorganisms? What follows is a digest of their efforts and the views of the author.


Infections of the neck leading to descending necrotizing mediastinitis: Role of multi-detector row computed tomography.
Descending necrotizing mediastinitis is an acute, polymicrobial infection of the mediastinum, originating from odontogenic, oropharyngeal and cervical infections. Anatomical continuity of the fascial spaces between the neck and the mediastinum leads to an occasional mediastinal extension of deep neck infection as a serious sequela. An understanding of the anatomy of the deep spaces of the neck and familiarity with the imaging findings in descending necrotizing mediastinitis may allow rapid diagnosis and treatment of this rare and life-threatening complication of deep neck space infection. In this article, we discuss the current role of radiology in diagnosing descending necrotizing mediastinitis, in determining the level of infection and the pathways of spread of infections from the neck to the mediastinum and in planning a successful treatment.


Computer-aided diagnosis of colorectal polyps using linked color imaging colonoscopy to predict histology.
We developed a computer-aided diagnosis (CAD) system based on linked color imaging (LCI) images to predict the histological results of polyps by analyzing the colors of the lesions. A total of 139 images of adenomatous polyps and 69 images of non-adenomatous polyps obtained from our hospital were collected and used to train the CAD system. A test set of LCI images, including both adenomatous and non-adenomatous polyps, was prospectively collected from patients who underwent colonoscopies between Oct and Dec 2017; this test set was used to assess the diagnostic abilities of the CAD system compared to those of human endoscopists (two experts and two novices). The accuracy, sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of this novel CAD system for the training set were 87.0%, 87.1%, 87.0%, 93.1%, and 76.9%, respectively. The test set included 115 adenomatous polyps and 66 non-adenomatous polyps that were prospectively collected. The CAD system identified adenomatous or non-adenomatous polyps in the test set with an accuracy of 78.4%, a sensitivity of 83.3%, a specificity of 70.1%, a PPV of 82.6%, and an NPV of 71.2%. The accuracy of the CAD system was comparable to that of the expert endoscopists (78.4% vs 79.6%; p = 0.517). In addition, the diagnostic accuracy of the novices was significantly lower to the performance of the experts (70.7% vs 79.6%; p = 0.018). A novel CAD system based on LCI could be a rapid and powerful decision-making tool for endoscopists.


Chromosomes in retinoblastoma patients.
In a series of eight patients with retinoblastoma, one was found to have a reciprocal translocation of chromosomes 1 and 13. The breakpoint on chromosome 13 is at band q12, which suggests that the retinoblastoma locus is less distal than previously thought.


Conformers of dehydrogenated glycine isomers.
We report a comprehensive ab initio investigation of the conformers of dehydrogenated glycine radicals using the STO-3G, 3-21G, and aug-cc-pVDZ (aVDZ) basis sets and the UHF and UMP2 (H2 N-CH-COOH and HN-CH2 -COOH) as well as MCSCF and MRCI (H2 N-CH2 -COO) methods via two different conformational search strategies generating initial structures for optimizations by (a) removing H atoms from glycine conformers and (b) scanning torsional angles describing internal rotation along the CC, CN, and CO (except for H2 N-CH2 -COO) bonds of the radicals. We find four H2 N-CH-COOH {InCH , IInCH , IIInCH , IVnCH } and seven HN-CH2 -COOH {IpNH , IIpNH , IIInNH , IVpNH VnNH , VIpNH , VIIpNH } conformers with classical(adiabatic) relative energies of {0.00(0.00), 1.57(1.55), 5.25(5.03), 9.85(9.72)} and {0.00(0.00), 0.78(1.06), 1.93(2.08), 3.34(3.16), 3.39(3.29), 5.00(4.86), 9.27(8.87)} kcal/mol, respectively, obtained with UCCSD(T)-F12b/aug-cc-pVTZ(+UCCSD(T)-F12b/aVDZ ZPE correction) and four H2 N-CH2 -COO {IpCOO , IInCOO , IIIpCOO , IVnCOO } conformers with MRCI-F12+Q/aVDZ(+MRCI/aVDZ ZPE correction) energies of {0.00(0.00), 1.65(1.64), 1.78(1.75), 2.21(2.21)} kcal/mol, where n and p denote C1 and Cs symmetry. The MRCI-F12+Q[UCCSD(T)-F12b] InCH → IpNH and InCH → IpCOO classical(adiabatic) isomerization energies are 18.51(17.32)[21.20(20.01)] and 31.88(31.66) kcal/mol, respectively.


Long-term outcome with the automatic implantable cardioverter-defibrillator.
The automatic implantable cardioverter-defibrillator was implanted in 270 patients because of life-threatening arrhythmias over a 7 year period. There was a history of sustained ventricular tachycardia or fibrillation, or both, in 96% of these patients, 80% had one or more prior cardiac arrests and 78% had coronary artery disease as their underlying diagnosis. The average ejection fraction was 34%, and 96% of these patients had had an average of 3.4 antiarrhythmic drug failures per patient before defibrillator implantation. There were four perioperative deaths and eight patients had generator infection or generator erosion, or both, during the perioperative period or during long-term follow-up. Concomitant antiarrhythmic drug therapy was given to 69% of patients. Shocks from the device were given to 58% of patients. and 20% received "problematic" shocks. The device was removed from 16 patients during long-term follow-up for a variety of reasons. There were 7 sudden cardiac deaths and 30 nonsudden cardiac deaths, 18 of which were secondary to congestive heart failure. The actuarial incidence of sudden death, total cardiac death and total mortality from all causes was 1%, 7% and 8%, respectively, at 1 year, and 4%, 24% and 26% at 5 years. The automatic implantable cardioverter-defibrillator nearly eliminates sudden death over a long-term follow-up period in a high risk group of patients. It has an acceptable rate of complications or problems, or both, and most late deaths in these patients are nonsudden and of cardiovascular origin.


Management of severe childhood hypertension with minoxidil: a controlled clinical study.
The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.


The influence of khat-chewing on birth-weight in full-term infants.
The leaves of the shrub Catha edulis (khat) are widely chewed as part of social life in several countries around the Red Sea and in East Africa. The leaves possess stimulant properties and are also used by pregnant women. The effect of khat on birth-weight has been studied, It was found that healthy full-term, singletons, born after uneventful pregnancies and deliveries, had a significantly lower average birth-weight when the mothers were khat-chewers, either habitually or occasionally (P less than 0.001). Khat-chewing appears to be one of several maternal practices adverse to the fetus.


Peroxisome proliferator-activated receptor-gamma ligand inhibition of RANTES production by human endometriotic stromal cells is mediated through an upstream promoter element.
To investigate the effect of peroxisome proliferator activated receptor-gamma (PPAR-gamma) ligands on transcription and secretion of regulated upon activation normal T-cell expressed and secreted (RANTES) in endometriotic stromal cells. Controlled laboratory study. Academic research laboratory. Women in the follicular phase of the menstrual cycle undergoing laparoscopic resection for endometriosis. [1]. Transient transfection of endometriotic stromal cells with RANTES promoter vectors with and without a mutagenized PPAR-gamma response element (PPRE), then treatment with PPAR-gamma ligands; [2]. co-incubation of cells with PPAR-gamma ligands. RANTES promoter activity and RANTES secretion. In endometriotic stromal cells, addition of PPAR-gamma ligands (rosiglitazone and 15 deoxy-Delta(12,14) prostaglandin J(2)) inhibited RANTES promoter activity by 51% and 50%, respectively. In cells transfected with the same promoter after site-directed mutagenesis of the 5' PPRE, addition of PPAR-gamma ligands failed to inhibit promoter activity. When endometriotic stromal cells were treated with PPAR-gamma ligands, a decrease in RANTES secretion by 51% and 20%, respectively, was observed. CONCLUION(S): The PPAR-gamma ligands inhibit RANTES transcription and protein production in endometriotic stromal cells. Transcriptional repression appears to be mediated through a specific PPRE at -344 to -322 bp upstream from the RNA polymerase start site.


LATERAL BRANCHING OXIDOREDUCTASE, one novel target gene of Squamosa Promoter Binding Protein-like 2, regulates tillering in switchgrass.
Strigolactones (SLs) play a critical role in regulating plant tiller number. LATERAL BRANCHING OXIDOREDUCTASE (LBO) encodes an important late-acting enzyme for SL biosynthesis and regulates shoot branching in Arabidopsis. However, little is known about the function of LBO in monocots including switchgrass (Panicum virgatum L.), a dual-purpose fodder and biofuel crop. We studied the function of PvLBO via the genetic manipulation of its expression levels in both the wild-type and miR156 overexpressing (miR156OE ) switchgrass. Co-expression analysis, quantitative real-time polymerase chain reaction (qRT-PCR), transient dual luciferase assay, and chromatin immunoprecipitation-qPCR were all used to determine the activation of PvLBO by miR156-targeted Squamosa Promoter Binding Protein-like 2 (PvSPL2) in regulating tillering of switchgrass. PvLBOtranscripts dramatically declined in miR156OE transgenic switchgrass, and the overexpression of PvLBO in the miR156OE transgenic line produce fewer tillers than the control. Furthermore, we found that PvSPL2 can directly bind to the promoter of PvLBO and activate its transcription, suggesting that PvLBO is a novel downstream gene of PvSPL2. We propose that PvLBO functions as an SL biosynthetic gene to mediate tillering and acts as an important downstream factor in the crosstalk between the SL biosynthetic pathway and the miR156-SPL module in switchgrass.


Radiomics Features at Multiparametric MRI Predict Disease-Free Survival in Patients With Locally Advanced Rectal Cancer.
To investigate the potential value of radiomics features based on preoperative multiparameter MRI in predicting disease-free survival (DFS) in patients with local advanced rectal cancer (LARC). We identified 234 patients with LARC who underwent preoperative MRI, including T2-weighted, diffusion kurtosis imaging, and contrast enhanced T1-weighted. All patients were randomly divided into the training (n = 164) and validation (n = 70) cohorts. 414 features were extracted from the tumor from above sequences and the radiomics signature was then generated, mainly based on feature stability and Cox proportional hazards model. Two models, integrating pre- and postoperative variables, were constructed to validate the radiomics signatures for DFS estimation. The radiomics signature, composed of six DFS-related features, was significantly associated with DFS in the training and validation cohorts (both p < 0.001). The radiomics signature and MR-defined extramural venous invasion (mrEMVI) were identified as the independent predictor of DFS both in the pre- and postoperative models. In both cohorts, the two radiomics-based models exhibited better prediction performance (C-index ≥0.77, all p < 0.05) than the corresponding clinical models, with positive net reclassification improvement and lower Akaike information criterion (AIC). Decision curve analysis also confirmed their clinical usefulness. The radiomics-based models could categorize LARC patients into high- and low-risk groups with distinct profiles of DFS (all p < 0.05). The proposed radiomics models with pre- and postoperative features have the potential to predict DFS, and may provide valuable guidance for the future individualized management in patients with LARC.


Informed choice in women attending private clinics to undergo first-trimester screening for Down syndrome.
Informed choice for prenatal screening has long been considered an essential aspect of service provision, and has been researched extensively in the second trimester. This study aims at examining whether women having first-trimester screening in a private clinic had made an informed choice. A cross-sectional survey recruited women having first-trimester screening at specialist ultrasound practices. Two questionnaires containing a validated Multidimensional Measure of Informed Choice (MMIC) were self-administered pre- and post-screening. MMIC was completed by 81% (163/202) of women. Ninety-nine percent of women had a positive attitude towards screening, therefore informed choice was essentially measured on knowledge alone. Pre-screening, 68% made an informed choice, compared with 74% post-screening (chi2 = 1.6, p = 0.21 (McNemar)). Knowledge was associated with education level, information sources and perception of screening as routine or optional. The Australasian Guidelines on prenatal screening state that all women having testing should be provided with written information, and it should be ensured that they have appropriate understanding of the test(s). These guidelines are not being met, even in private clinical care. Health professionals should ensure that all women are provided with suitable information about prenatal screening that is tailored to their level of education and individual needs, and should emphasise that screening is optional.


Electrostatic effects on the electrical tension-induced irreversible pore formation in giant unilamellar vesicles.
Irreversible electroporation (IRE) is a new technique in which a series of short pulses with high frequency electrical energy is applied on the targeted regions of cells or vesicles for their destruction or rupture formation. IRE induces lateral tension in the membranes of vesicles. We have investigated the electrostatic interaction effects on the constant electrical tension-induced rate constant of irreversible pore formation in the membranes of giant unilamellar vesicles (GUVs). The electrostatic interaction has been varied by changing the salt concentration in buffer and the surface charge density of membranes. The membranes of GUVs are synthesized by a mixture of negatively charged lipid dioleoylphosphatidylglycerol (DOPG) and neutral lipid dioleoylphosphatidylcholine (DOPC) using the natural swelling method. The rate constant of pore formation increases with the decrease of salt concentration in buffer along with the increase of surface charge density of membranes. The tension dependent probability of pore formation and the rate constant of pore formation are fitted to the theoretical equation, and obtained the line tension of membranes. The decrease in energy barrier of a prepore due to electrostatic interaction is the key factor causing an increase of rate constant of pore formation.


Repair of DNA damage induced by the mycotoxin alternariol involves tyrosyl-DNA phosphodiesterase 1.
Alternariol (AOH) was reported recently to act as a topoisomerase poison. To underline the relevance of topoisomerase targeting for the genotoxic properties of AOH, we addressed the question whether human tyrosyl-DNA phosphodiesterase 1 (TDP1), an enzyme vital to the repair of covalent DNA-topoisomerase adducts, affects AOH-mediated genotoxicity. The relevance of TDP1 activity on AOH-induced genotoxicity was investigated by the comet assay in human cells overexpressing GFP chimera of TDP1 or the inactive mutant TDP1(H263A) as well as in cells subjected to siRNA-mediated knock-down of endogenous TDP1. Cells overexpressing TDP1 exhibited significantly less DNA damage after treatment with AOH in comparison to cells expressing the inactive mutant TDP1(H263A). In accordance with these results, levels of AOH inducing DNA strand breaks were increased in TDP1-suppressed cells in comparison to cells transfected with control siRNA. The specific topoisomerase poisons camptothecin and etoposide caused comparable effects, underlining that TDP1 plays an important role in the repair of topoisomerase-mediated DNA damage. In summary, the repair enzyme TDP1 was identified as a factor for the modulation of AOH-mediated DNA damage in human cells.


Scattering of a Laser Beam on an Ensemble of Asymmetrical Erythrocytes.
The study describes an analytical model of laser beam scattering on an inhomogeneous ensemble of erythrocytes. The model takes into account erythrocyte variation in size, shape, and spatial orientation. A relationship is established between an experimentally determined parameter: visibility of the diffraction pattern, and a characteristic serving as a measure of inhomogeneity of erythrocyte size and shape in a blood specimen. This relationship is shown to be monotonous, which means that erythrocyte variation in size and shape can be assessed based on measurements of the diffraction pattern visibility.


Signet-ring cell adenocarcinoma metastatic to the maxillary sinus.
Signet-ring cell variant is a rare type of adenocarcinoma that has been reported in the paranasal sinuses and in other areas, most commonly the gastrointestinal tract. We describe a patient with signet-ring cell adenocarcinoma of the maxillary sinus who had dental and facial pain. Further evaluation revealed that the lesion was metastatic from an esophageal primary lesion. The unusual nature of this cell type and the importance of careful evaluation to exclude the possibility of these lesions representing metastatic lesions is discussed.


Combined first pass and equilibrium radionuclide cardiographic determination of stroke volume for quantitation of valvular regurgitation.
A new noninvasive procedure for quantitation of cardiac valve regurgitation was evaluated using a combination of first pass and gated equilibrium radionuclide cardiography in 38 subjects with and without cardiac valve disease. Left-sided cardiac catheterization was performed to determine the severity of mitral incompetence and aortic regurgitation semiquantitatively. In healthy subjects and in patients without valve disease, stroke volumes were nearly identical with the two methods and the correlation was high (r = 0.98 [p less than 0.001]). The mean regurgitation fraction was 13% in patients with mild mitral incompetence and 2+ aortic regurgitation, 37% in patients with moderate mitral incompetence and 3+ aortic regurgitation and 57% in patients with severe mitral incompetence and 4+ aortic regurgitation. These findings suggest that combined first pass and gated equilibrium radionuclide cardiography, being insensitive to intracardiac shunts and right-sided valve disorders, constitutes a valid noninvasive technique for quantitation of left-sided cardiac valve regurgitation.


Spatial distribution of excitatory innervation on a muscle fiber of the lobster (Homarus americanus).
The distribution of nerve terminals from a single excitatory motor axon has been followed along a fiber from the proximal accessory flexor muscle of the lobster by thin serial sectioning at periodic intervals. The excitatory motor axon provides small axonal branches (diameter 5--12 micron) of varying lengths that travel along the surface of the muscle fiber. Each of these branches gives rise to discrete synaptic terminals which are not uniformly distributed. Individual terminals vary in length from 10--60 micron and the majority possess neuromuscular synapses. The greatest distance between synapses is slightly over 1 mm which is well within the length constant (2.6 mm) of this muscle fiber. Thus the spatail distribution of synapses is such as to ensure adequate depolarization along the entire length of the muscle fiber.