Simple solution for failure of trailing sutures when using the EndoButton in anterior cruciate ligament reconstruction: the "Rescue Rein".
In this article, we introduce the technique of adding a second suture in the distal hole of the EndoButton. This suture, the "Rescue Rein," is kept with the graft and is a simple solution for recovering the graft during anterior cruciate ligament reconstruction when the EndoButton becomes jammed within the femoral tunnel and the trailing sutures cannot be removed.


Urban Trees in Times of Crisis: Palliatives, Mitigators, and Resources.
Trees have been integral to cities for centuries. Their tangible and intangible benefits for human and environmental systems are particularly evident in times of crisis. As cities grow and adapt to climate change, historical, scientific, and practical expertise are needed to ensure equal access to urban trees and their benefits.


Effects of autoclaving and charcoal on root-promoting substances present in water extracts made from gelling agents.
The root-promoting ability of water extracts made from gelling agents (agar and Gelrite) was investigated using the mungbean rooting bioassay. Autoclaving these water extracts decreased the number of roots in mungbean cuttings compared to the controls. The addition of activated charcoal to the water extracts from Agar Bacteriological and Agar Commercial Gel had no effect on their root-promoting ability. Extracts with exogenous indole-3-butyric acid (IBA) which were treated by autoclaving or via a freeze-thaw cycle, significantly increased rooting. However, incorporation of activated charcoal to similar IBA-containing extracts reduced rooting. Our results indicate that more attention should be given to the choice of gelling agent and its interaction with other additives in the media used during tissue culture.


Response assessment using [68 Ga]Ga-PSMA ligand PET in patients undergoing systemic therapy for metastatic castration-resistant prostate cancer.
To assess which parameters of [68 Ga]Ga-PSMA-11 positron emission tomography (PSMA-PET) predict response to systemic therapies in metastatic (m) castration-resistant prostate cancer (CRPC). In addition, to investigate which of these factors are associated with overall survival (OS). We retrospectively assessed the following PSMA-PET parameters in 43 patients before and after systemic therapies for mCRPC: PSMA total tumor volume (TTV), mean standardized uptake value (SUVmean), SUVmax, and SUVpeak. prostate-specific antigen (PSA) levels and PSMA-PET/CT(magnetic resonance imaging [MRI]) imaging were both performed within 8 weeks before and 6 weeks after systemic therapy. PSMA-PET and CT (MRI) images were reviewed according to the modified PET Response Criteria in Solid Tumors (PERCIST) and Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Results were compared to PSA response. Univariable survival analyses were performed. Overall, 43 patients undergoing 67 systemic therapies were included (9 patients radium-223, 12 cabazitaxel, 22 docetaxel, 6 abiraterone, and 18 enzalutamide). Median serum PSA level before any therapy was 11.3 ng/mL (interquartile range [IQR] = 3.3, 30.1). Delta (d) PSA after systemic therapies was -41%, dTTV 10.5%, dSUVmean -7.5%, dSUVmax -13.3%, dSUVpeak -12%, and dRECIST -13.3%. Overall, 31 patients had dPSA response (46.3%), 12 stable disease (17.9%), and 24 progressive disease (35.8%). All observed PET parameters, as well as the RECIST evaluation, were significantly associated with PSA response (dTTV P = .003, dSUVmean P = .003, dSUVmax P = .011, dSUVpeak P < 0001, dRECIST P = .012), while RECIST assessment was applicable in 37 out of 67 patients (55.2%). Within a median follow-up of 33 months (IQR = 26, 38), 10 patients (23.3%) died of PC. On univariable survival analyses, neither the investigated PET parameters nor PSA level or RECIST criteria were associated with OS. PSMA-PET provides reliable parameters for prediction of response to systemic therapies for mCRPC. These parameters, if confirmed, could enhance RECIST criteria, specifically concerning its limitations for sclerotic bone lesions.


What You're Rejecting When You're Expecting.
I defend two collapsing or reductionist arguments against weak pro-natalism (WPN), the view that procreation is generally merely permissible. In particular, I argue that WPN collapses into strong pro-natalism (SPN), the view that procreation is generally obligatory. Because SPN conflicts with the dominant view that procreation is never obligatory, demonstrating that WPN collapses into or entails SPN establishes epistemic parity (at least as concerns reproductive liberty) between WPN and anti-natalism (AN), the view that procreation is always impermissible. First, I distinguish between two moral goods: the good of procreation itself and the good of procreative potential. Second, I contend that the average moral agent is obligated to assist needy children via adoption, fostering, or other financial or interpersonal support. Third, I present the first collapsing argument: if an agent's justification for not assisting needy children is preservation of their resources (financial or interpersonal) for their actual future offspring, that justification is preserved only if they eventually and actually procreate. Thus, their eventual procreation is morally obligatory and SPN follows. Fourth, I present the second collapsing argument, which assumes procreative potential as the relevant good: if an agent's justification for not assisting needy children is preservation of their resources for their potential future offspring, that justification holds only if (a) the objective or subjective valuation of the opportunity is of the relevant type and valence to justify not assisting needy children and (b) the agent sincerely values the opportunity. Fifth, I argue that (a) is unsatisfied and that while (b) is satisfied in most cases, it entails that most agents are obligated to desire or be behaviourally disposed to pursue procreation for themselves (i.e., SPN). Thus, I conclude that both actual procreation and procreative potential are either insufficient justifications for not assisting needy children or that they entail obligatory pro-reproductive attitudes or behaviours.


Organophosphates modulate tissue transglutaminase activity in differentiated C6 neural cells.
The organophosphate compounds chlorpyrifos (O, O-diethyl O-[3,5,6-trichloro-2-pyridinyl] phosphorothioate, CPF) and phenyl saligenin phosphate (PSP) have been widely implicated in developmental neurotoxicity and neurodegeneration. However, the underlying mechanism remains unclear. Transglutaminase (TG)2 is a calcium ion (Ca2+)-dependent enzyme with an important role in neuronal cell outgrowth and differentiation and in neurotoxin activity and is modulated by organophosphates. We studied TG2 activity modulation by CPO and PSP during differentiation in C6 glioma cells. We studied the effects of CPO or PSP treatment with or without the TG2 inhibitor Z-DON and identified potential TG2 protein substrates via mass spectrometry. PSP and CPO did not affect cell viability but affected TG2 activity in differentiating cells. Our results indicate that the organophosphate-induced amine incorporation activity of TG2 may have a direct effect on neuronal outgrowth, differentiation, and cell survival by modifying several essential microtubule proteins, including tubulin. Inhibiting TG2 reduced neurite length but not cell survival. TG2 inhibitors can protect against organophosphate-induced neuropathy and could be used for developing novel therapeutic strategies for treating brain cancer and neurodegenerative disorders.


Degradation synergism between sonolysis and photocatalysis for organic pollutants with different hydrophobicity: A perspective of mechanism and application for high mineralization efficiency.
Despite extensive studies, the fundamental understanding of synergistic mechanisms between sonolysis and photocatalysis for the abatement of persistent organic pollutants (POPs) remains uncertain. As different phases formed under ultrasound irradiation, hydrophilic POPs, sulfamethoxazole (SMX, Kow: 0.89), predominantly resides in bulk liquid and is ineffectively degraded by sonolysis (kUS = 3.33 × 10-3 min-1) since <10% of hydroxyl radicals (·OH) formed at the gas-liquid interface of cavitation is diffused into the bulk, whereas the other fraction rapidly recombines into hydrogen peroxide (H2O2). This study provides a proof-of-concept for the mechanism by presenting various analytical results, endorsing the synergistic role of photoexcited electrons in splitting sonolysis-induced H2O2 into ·OH, particularly in the bulk phase. In a sonophotocatalytic system, the hydrophobic POPs such as bisphenol A (BPA) and atrazine (ATZ) were mainly degraded in gas-liquid interface indicated by the low synergistic values correlation compared to SMX [i.e., SMX has a higher synergistic factor, fsyn (3.26) than BPA (1.30) and ATZ (1.35)]. Also, fsyn was found linearly correlated with the contribution factor of photocatalysis to split H2O2. Three times of consecutive kinetics using an effluent of municipal (MP) wastewater spiked by POPs presented >98% POPs and >96% total organic carbon (TOC) removal.


Combined PD-1/VEGFR Blockade: A New Era of Treatment for Hepatocellular Cancer.
Combination immunotherapy is an expanding therapeutic modality in hepatocellular carcinoma (HCC), a disease where single-agent immunotherapy has failed to lead to survival benefit. The RESCUE trial adds camrelizumab and apatinib to the therapeutic armamentarium of advanced HCC, raising questions around the optimal positioning of various combination regimens in liver cancer.See related article by Xu et al., p. 1003.


Arthroscopic nomenclature of capsulolabral appearances in anterior shoulder dislocation.
To study the intraoperative morphology of the glenoid labrum and capsule in recurrent shoulder dislocation and to study the relationship between the number of dislocations and the changes in the glenoid and labrum. Over a period of 18 months, 108 patients with traumatic anterior dislocations were included in the study, of which 102 men and 6 women with mean age of 33.4yrs range from 18 to 45. The patients with bony bankart, other labral lesions, ligamentous laxity, SLAP tear were excluded from the study. All the patients underwent arthroscopic bankart repair. We have classified the morphology of labrum and capsule on their appearance intraoperatively. Labrum is named as Normal, Desiccated or Shredded and Capsule as Normal or Damaged. Six varieties of appearances were observed. Namely, Normal capsule and Normal labrum (NN), Normal capsule and Desiccated labrum (ND), Normal capsule and Shredded labrum (NS), Damaged capsule and Normal labrum (DN), Damaged capsule and Desiccated labrum(DD), Damaged capsule and Shredded labrum(DS). Among them, DD (33.3%) and DS (29.6%) variety had highest number of dislocations suggesting the labrum and capsule lose normal anatomy with more recurrence of dislocations. These findings support that reproducing normal anatomy after surgical repair is possible when the intervention is done sooner than later. III.


Nivolumab versus everolimus in advanced renal cell carcinoma: Japanese subgroup analysis from the CheckMate 025 study.
Nivolumab improved overall survival (OS) and objective response rate (ORR) versus everolimus in previously treated patients with advanced renal cell carcinoma in the phase III CheckMate 025 study (minimum follow-up: 14 months). We report efficacy and safety in the global and Japanese populations (minimum follow-up: 26 months). Patients were randomized 1:1 to receive nivolumab 3 mg/kg intravenously every 2 weeks or everolimus 10-mg tablet orally once daily. Primary endpoint: OS, key secondary endpoints: ORR, progression-free survival and safety. Of 410 (nivolumab) and 411 (everolimus) patients, 37 (9%) and 26 (6%), respectively, were Japanese. Median OS for the global population was 26.0 months (nivolumab) and 19.7 months (everolimus; hazard ratio 0.73 [95% confidence interval [CI]: 0.61-0.88]; P = 0.0006), with medians not reached for Japanese patients. ORR for the global population was 26% (nivolumab) versus 5% (everolimus; odds ratio 6.13; 95% CI: 3.77-9.95); ORR for Japanese patients: 43% versus 8% (odds ratio 9.14; 95% CI: 1.76-88.33). In Japanese patients, any-grade treatment-related adverse events (AEs) occurred in 78% (Grade 3-4, 19%; most common, anemia [5%]) treated with nivolumab and 100% (Grade 3-4, 58%; most common, hypertriglyceridemia [12%]) treated with everolimus; the most common with nivolumab was diarrhea (19%) and with everolimus was stomatitis (77%). Quality of life was stable in the nivolumab arm. With >2 years of follow-up, Japanese patients had a higher response rate with nivolumab versus everolimus that was more pronounced yet consistent with the global population, with median OS not reached, and a favorable safety profile.


Investigation of colorimetric biosensor array based on programable surface chemistry of M13 bacteriophage towards artificial nose for volatile organic compound detection: From basic properties of the biosensor to practical application.
Various threats such as explosives, drugs, environmental hormones, and spoiled food manifest themselves with the presence of volatile organic compounds (VOCs) in our environment. In order to recognize and respond to these threats early, the demand for highly sensitive and selective electronic noses is increasing. The M13 bacteriophage-based optoelectronic nose is an excellent candidate to meet all these requirements. However, the phage-based electronic nose is still in its infancy, and strategies that include a systematic approach and development are still essential. Here, we have integrated theoretical and experimental approaches to analyze the correlation between the surface chemistry of genetically engineered phage and the phage-based optoelectronic nose properties. The reactivity of the genetically engineered phage color film to some VOCs were quantitatively analyzed, and the correlation with the binding affinity value calculated by Density-functional theory (DFT) was compared. This demonstrates that phage color films have controllable reactivity through a genetic engineering. We have selected phages that are advantageous in distinguishing each VOCs in this work through hierarchical cluster analysis (HCA). The reason for this difference was verified through the optimized geometry calculated by DFT. Through this, it was confirmed that the tryptophan-based and the Histidine-based of genetically engineered phage film are important in distinguishing the VOCs (Y-hexanolactone, 2-isopropyl-4-methylthiazole, ethanol, acetone, ethyl acetate, and acetaldehyde) used in this work to evaluate the peach freshness quality. This was applied to the design of a field-applied phage-based optoelectronic nose and verified by measuring the freshness of the actual fruit.


[Analysis of dissertations on the diagnosis and treatment of gynecologic diseases that were defended in the Russian Federation and accepted by the Russian Federation Higher Certifying Committee].
The paper outlines major achievements in researches in the diagnosis and treatment of gynecological diseases and analyzes the theses defended. It also gives recommendations for further planning of dissertations.


Is orthodontic treatment associated with changes in self-esteem during adolescence? A longitudinal study.
This study explored the association between history of orthodontic treatment and changes in self-esteem among British adolescents. Birth cohort study. United Kingdom. Data from 2600 participants of the British Cohort Study were analysed. Participants completed the Lawrence Self-Esteem Questionnaire (LAWSEQ) at the ages of 10 and 16 years. The change in LAWSEQ score over six years was the outcome. Participants were divided into two groups according to parental reports of orthodontic treatment at the same ages. The association between history of orthodontic treatment and six-year changes in LAWSEQ score was tested in linear regression models adjusting for demographic factors (adolescents' sex and ethnicity), family socioeconomic status (parental social class and mothers' education), perceived orthodontic treatment need and baseline LAWSEQ score. According to parental reports, 8% of participants had a history of orthodontic treatment. The mean LAWSEQ score at baseline was 13.7 (95% confidence interval [CI] 13.6-13.9) and increased significantly over time by 1.7 units (95% CI 1.5-1.9). Orthodontic treatment history was positively, albeit not significantly, associated with change in LAWSEQ score (coefficient: 0.08, 95% CI -0.56 to 0.72). The direction of the association reversed but remained non-significant after adjustment for all confounders (coefficient: -0.19; 95% CI -0.68 to 0.30). Improvements in self-esteem were positively associated with mothers' education (coefficient: 0.85; 95% CI 0.09-1.61) and negatively associated with self-esteem at baseline (coefficient -0.79; 95% CI -0.82 to -0.75). This six-year longitudinal study provided no evidence for an association between history of orthodontic treatment and changes in self-esteem during adolescence.


The Smoker's Paradox Revisited: A Patient-Level Pooled Analysis of 18 Randomized Controlled Trials.
This study examined the smoker's paradox using patient-level data from 18 prospective, randomized trials of patients undergoing percutaneous coronary intervention (PCI) with stent implantation. Studies on the effects of smoking and outcomes among patients undergoing PCI have reported conflicting results. Data from the RAVEL, E-SIRIUS, SIRIUS, C-SIRIUS, TAXUS IV and V, ENDEAVOR II to IV, SPIRIT II to IV, HORIZONS-AMI, COMPARE I and II, PLATINUM, and TWENTE I and II randomized trials were pooled. Patients were stratified by smoking status at time of enrollment. The 1- and 5-year ischemic outcomes were compared. Among 24,354 patients with available data on smoking status, 6,722 (27.6%) were current smokers. Smokers were younger and less likely to have diabetes mellitus; hypertension; hyperlipidemia; or prior myocardial infarction (MI), PCI, or coronary artery bypass grafting. Angiographically, smokers had longer lesions, more complex lesions, and more occlusions, but were less likely to have moderate or severe calcification or tortuosity. At 5 years, smokers had significantly higher rates of MI (7.8% vs. 5.6%; p < 0.0001) and definite or probable stent thrombosis (3.5% vs. 1.8%; p < 0.0001); however, there were no differences in the rates of death, cardiac death, target lesion revascularization, or composite endpoints (cardiac death, target vessel MI, or ischemic target lesion revascularization). After multivariable adjustment for potential confounders, smoking was a strong independent predictor of death (hazard ratio [HR]: 1.86; 95% confidence interval [CI]: 1.63 to 2.12; p < 0.0001), cardiac death (HR: 1.68; 95% CI: 1.38 to 2.05; p < 0.0001), MI (HR: 1.38; 95% CI: 1.20 to 1.58; p < 0.0001), stent thrombosis (HR: 1.60; 95% CI: 1.28 to 1.99; p < 0.0001), and target lesion failure (HR: 1.17; 95% CI: 1.05 to 1.30; p = 0.005). The present large, patient-level, pooled analysis with 5-year follow-up clearly demonstrates smoking to be an important predictor of adverse outcomes after PCI.


2'-Iodo-2,2'',3,3'',4,4'',5,5'',6,6''-deca-methyl-1,1':3',1''-terphenyl chloro-form monosolvate.
The title compound, C(28)H(33)I·CHCl(3), forms dimers through C-I⋯π inter-actions. The crystal structure is consolidated by the presence of C-H⋯π inter-actions between the chloro-form solvent and the main mol-ecule.


Bone formation by cancer metastases: case report and review of literature.
The formation of heterotopic bone tissue in malignant tumors or in their metastases is extremely rare. In a 60 years old male patient with bronchogenic carcinoma (adenocarcinoma) extensive bone formation was observed within multiple metastases in the skeletal muscles. On the basis of the microscopic findings, the mechanism of bone formation by malignant tumors is discussed. Obviously, proliferation of local mesenchymal tissue and differentiation of mesenchymal cells to osteoblasts is induced by the tumor cells.


Comparative studies on the structural proteins of T3 and T7 phages.
A comparison of the coat protein patterns of the wild types of the related phages T3 and T7 on SDS polyacrylamide gel electrophoresis was carried out. After infection of the nonpermissive host with T7 amber mutants in genes 7, 11, 12, 13 or 17 and T3 amber mutants in genes 11, 12, 13 and 17 respectively, noninfectious, DNA containing particles were produced. The protein pattern, as well as electron microscopy of defective particles of T3 and T7 led to the conclusion that the proteins specified by genes 11, 12, 13 and 17 are tail proteins whereas the proteins coded by genes 7, 8, 10, 14, 15 and 16 enter the head structure. The "serum blocking protein" (gene 17 product) seems to play a different role in the assembly of T3 and T7 tails, since T3 particles defective in gene 17 did not show any tail structure connected with the head whereas T7 particles defective in gene 17 had a tail which looked different from that of the wildtype. Treatment of wildtype particles with ammonium nitrate or sodium pyrophosphate led to morphologically abberrant forms which had partially or completely lost the hexagonal head structure. After treatment with ammonium nitrate ball-like structures were obtained, both for T3 and T7. However, in the case of T3 these abberrant forms contained the proteins specified by genes 7, 8 and 10 whereas those derived from T7 contained only the proteins specified by genes 8 and 10. Sodium pyrophosphate treatment of T3 and T7 wildtype particles led to a release of the phage tails. The isolated tails were examined by electron microscopy thus revealing for the first time a detailed substructure of the T3 and T7 phage tails. In order to find out more about the tail proteins, absorption experiments with isolated bacterial cell walls were carried out.


Novel Gain-of-Function Mutation in Stat1 Sumoylation Site Leads to CMC/CID Phenotype Responsive to Ruxolitinib.
Mutations in the coiled-coil and DNA-binding domains of STAT1 lead to delayed STAT1 dephosphorylation and subsequently gain-of-function. The associated clinical phenotype is broad and can include chronic mucocutaneous candidiasis (CMC) and/or combined immunodeficiency (CID). We report a case of CMC/CID in a 10-year-old boy due to a novel mutation in the small ubiquitin molecule (SUMO) consensus site at the C-terminal region of STAT1 leading to gain-of-function by impaired sumoylation. Immunodysregulatory features of disease improved after Janus kinase inhibitor (jakinib) treatment. Functional testing after treatment confirmed reversal of the STAT1 hyper-phosphorylation and downstream transcriptional activity. IL-17 and IL-22 production was, however, not restored with jakinib therapy (ruxolitinib), and the patient remained susceptible to opportunistic infection. In conclusion, a mutation in the SUMO consensus site of STAT1 can lead to gain-of-function that is reversible with jakinib treatment. However, full immunocompetence was not restored, suggesting that this treatment strategy might serve well as a bridge to definitive therapy such as hematopoietic stem cell transplant rather than a long-term treatment option.


Isolated nocardial brain abscess in an immunocompetent patient with lung adenocarcinoma: A case report.
Brain metastases are common in non-small cell lung cancer (NSCLC) and can often be the presenting symptom. However, it is important to consider other etiologies for brain masses even in patients with a malignancy with a propensity to metastasize. We discuss the case of a 60 year-old immunocompetent male who presented with neurologic deficits thought to be secondary to brain metastases in the setting of an incidentally discovered lung cancer. Instead, the mass proved to be a rare isolated Nocardial brain abscess.


Tracheostomy timing and outcome in critically ill patients with stroke: a meta-analysis and meta-regression.
Stroke patients requiring mechanical ventilation often have a poor prognosis. The optimal timing of tracheostomy and its impact on mortality in stroke patients remains uncertain. We performed a systematic review and meta-analysis of tracheostomy timing and its association with reported all-cause overall mortality. Secondary outcomes were the effect of tracheostomy timing on neurological outcome (modified Rankin Scale, mRS), hospital length of stay (LOS), and intensive care unit (ICU) LOS. We searched 5 databases for entries related to acute stroke and tracheostomy from inception to 25 November 2022. We adhered to PRISMA guidance for reporting systematic reviews and meta-analyses. Selected studies included (1) ICU-admitted patients who had stroke (either acute ischaemic stroke, AIS or intracerebral haemorrhage, ICH) and received a tracheostomy (with known timing) during their stay and (2) > 20 tracheotomised. Studies primarily reporting sub-arachnoid haemorrhage (SAH) were excluded. Where this was not possible, adjusted meta-analysis and meta-regression with study-level moderators were performed. Tracheostomy timing was analysed continuously and categorically, where early (< 5 days from initiation of mechanical ventilation to tracheostomy) and late (> 10 days) timing was defined per the protocol of SETPOINT2, the largest and most recent randomised controlled trial on tracheostomy timing in stroke patients. Thirteen studies involving 17,346 patients (mean age = 59.8 years, female 44%) met the inclusion criteria. ICH, AIS, and SAH comprised 83%, 12%, and 5% of known strokes, respectively. The mean time to tracheostomy was 9.7 days. Overall reported all-cause mortality (adjusted for follow-up) was 15.7%. One in five patients had good neurological outcome (mRS 0-3; median follow-up duration was 180 days). Overall, patients were ventilated for approximately 12 days and had an ICU LOS of 16 days and a hospital LOS of 28 days. A meta-regression analysis using tracheostomy time as a continuous variable showed no statistically significant association between tracheostomy timing and mortality (β = - 0.3, 95% CI = - 2.3 to 1.74, p = 0.8). Early tracheostomy conferred no mortality benefit when compared to late tracheostomy (7.8% vs. 16.4%, p = 0.7). Tracheostomy timing was not associated with secondary outcomes (good neurological outcome, ICU LOS and hospital LOS). In this meta-analysis of over 17,000 critically ill stroke patients, the timing of tracheostomy was not associated with mortality, neurological outcomes, or ICU/hospital LOS. PROSPERO-CRD42022351732 registered on 17th of August 2022.


Non-target trend analysis for the identification of transformation products during ozonation experiments of citalopram and four of its biodegradation products.
During ozonation in wastewater treatment plants, ozone reacts with emerging pollutants, which are partially removed through the secondary treatment, as long as, with their biotransformation products, triggering the formation of ozonation transformation products (TPs). Although the transformation of parent compounds (PCs) and their metabolites has been reported in the literature, the probable transformation of biotransformation products has not been investigated so far. This study evaluates the fate of citalopram (CTR) and four of its biotransformation products (DESCTR, CTRAM, CTRAC and CTROXO) during ozonation experiments. A Gaussian curve-based trend analysis was performed for the first time for the automated detection of TPs in ozone concentrations ranging from 0.06 to 12 mg/L. In total 46 ozonation TPs were detected; 7 TPs of CTR, 10 of DESCTR, 9 of CTRAM, 12 of CTRAC and 8 of CTROXO and were structurally elucidated based on their high resolution tandem mass spectra interpretation and tandem mass spectra similarity with the respective PC. Results have demonstrated that the examined compounds follow common transformation pathways in reaction with ozone and that common TPs were formed through the ozonation of different structurally-alike compounds. Moreover, the toxicity of the identified TPs was predicted with an in-house risk assessment program.


Measuring for change: A multi-centre pre-post trial of an air quality feedback intervention to promote smoke-free homes.
Second-hand smoke exposure in the home is a serious cause of ill-health for children. Behaviour change interventions have been developed to encourage parents to keep homes smoke-free. This study evaluates a novel air quality feedback intervention using remote air quality monitoring with SMS and email messaging to promote smoke-free homes among families from deprived areas. This paper presents a pre-post study of this intervention. Using internet connected monitors developed with the Dylos DC1700, daily SMS and weekly email feedback provided for 16 days to participants recruited in four European countries. Participants were recruited based on their stage of change, in order to target those most able to achieve smoke-free homes. The primary outcome measure was median change in mean fine particulate matter (PM2.5) concentration between baseline and follow-up periods, while secondary outcome measures included change in time over the World Health Organisation (WHO) guideline limit for PM2.5 exposure over 24 h (25 µg/m3) in those periods and the number of homes where PM2.5 concentrations reduced. Telephone interviews were conducted with participants in Scotland post-intervention to explore intervention experience and perceived effectiveness. Of 86 homes that completed the intervention study, 57 (66%) experienced pre-post reductions in measured PM2.5. The median reduction experienced was 4.1 µg/m3 (a reduction of 19% from baseline, p = 0.008). Eight homes where concentrations were higher than the WHO guideline limit at baseline fell below that level at follow-up. In follow-up interviews, participants expressed positive views on the usefulness of air quality feedback. Household air quality monitoring with SMS and email feedback can lead to behaviour change and consequent reductions in SHS in homes, but within the context of our study few homes became totally smoke-free.


Cramming versus threading of long amphiphilic oligomers into a polyaromatic capsule.
Oligo(ethylene oxide)s are known as widely useable yet not very interactive amphiphilic compounds. Here we report that the long amphiphilic oligomers are bound by a polyaromatic capsule in two different manners, depending on the chain length. For instance, the shorter pentamer is crammed into the isolated cavity of the capsule, whereas the longer decamer is threaded into the capsule to form a 1:1 host-guest complex in a pseudo-rotaxane fashion. These unusual bindings occur instantly, spontaneously, and quantitatively even in water at room temperature, with relatively high binding constants (Ka > 106 M-1). Isothermal titration calorimetry (ITC) studies reveal that enthalpic stabilization is a dominant driving force for both of the complexations through multiple host-guest CH-π and hydrogen-bonding interactions. Furthermore, long oligomers with an average molecular weight of 1000 Da (e.g., 22-mer) are also threaded into the capsules to give pseudo-rotaxane-shaped 2:1 host-guest complexes in water, selectively.


Inactivation of the p53 protein in cell lines derived from human esophageal cancers.
Alteration of the p53 gene is thought to be important in the early stages of human esophageal cancers, but how this confers a selective advantage to esophageal cancer cells is unknown. In this report, we analyzed 9 cell lines derived from human esophageal cancers (TE-1, TE-3, TE-6, TE-7, TE-9, TE-10, TE-11, TE-13 and TE-15) for mutations in the p53 sequence, p53 protein expression and p53 protein DNA-binding activity. The cell lines could be grouped in 3 categories, including (1) cell lines with mis-sense mutations in the coding sequence and accumulation of mutant proteins (TE-1, TE-6, TE-10 and TE-11); (2) cell lines expressing truncated forms of p53 as a result of frameshift (TE-9) or splice-site (TE-15) mutations; and (3) cell lines with wild-type p53 sequences but with impaired expression of p53 mRNA and protein, suggesting that p53 is inactivated by transcriptional repression (TE-3, TE-7 and TE-13). With the exception of TE-1, none of the cell lines exhibited p53-DNA-binding activity. In TE-1, a mutation at codon 272 (methionine to valine) generated a protein that retains basal DNA-binding activity, but that was not activated in response to DNA damage, suggesting that this mutation prevented p53 induction by genotoxic stress. Thus, p53 activity was impaired in all esophageal cell lines, including those containing wild-type p53 sequences.


Innovations in Diagnostic Imaging in Oral and Maxillofacial Diseases.
In recent years, improvements in imaging techniques have profoundly facilitated the diagnosis of pathologies of the maxillofacial district [...].


The carcinogenicity of lead.
The potential for lead to cause neoplasm in animals and man is reviewed. A multitude of studies indicate that principally renal tumours may be produced by various forms of inorganic lead in small rodents. No human study either of an epidemiological form or of a case report in industrial, agricultural or community medicine has proven that lead may cause cancer in man.


A clinical and biochemical score for mortality prediction in patients with acute dyspnoea: derivation, validation and incorporation into a bedside programme.
Risk stratification for patients with acute dyspnoea is a challenging task. No quantitative tool for mortality prediction among patients with acute dyspnoea is available. 595 dyspnoeic subjects were enrolled in an emergency department. Clinical and biochemical factors independently predictive of death by 1 year were used to develop a mortality risk prediction tool. Seven factors comprised the final tool: age (x0.3), heart rate (x0.2), blood urea nitrogen (x0.3), New York Heart Association class (x5), amino-terminal pro-B-type natriuretic peptide (NT-proBNP) >or=986 pg/ml (18 points), systolic blood pressure <100 mm Hg (11 points) and presence of a murmur (11 points). A continuous rise in mortality was seen from 1.7% in the lowest score quintile (n = 118; score <or=48.5) to 43.1% in the highest quintile (n = 116, score >or=85.5; p<0.001 for trend). Receiver operating characteristic curve analysis of the score's accuracy produced an area under the curve (AUC) of 0.82 (95% CI 0.78 to 0.85) with similar AUCs in subjects with acutely destabilised heart failure (AUC = 0.73, 95% CI 0.67 to 0.79) and those without (AUC = 0.83, 95% CI 0.77 to 0.85, p for the comparison = NS). The score was validated in a separate population of dyspnoeic patients (AUC = 0.73, 95% CI 0.64 to 0.82; p<0.001) and was incorporated into a computer program suitable for near-patient calculation. A new risk stratification tool for acutely dyspnoeic patients has been derived and validated.


Educating staff nurses on diabetes: knowledge enhancement.
Evidence-based practice education of staff nurses has the potential to improve knowledge and ultimately the care of hospitalized diabetic patients. The value and knowledge enhancement of a diabetes education program for nurses working in a Heart and Vascular Institute in an academic medical center is described.


Laparoscopic sleeve gastrectomy versus Roux-en-Y gastric bypass for quality of life: a systematic review and meta-analysis.
Laparoscopic sleeve gastrectomy (LSG) and laparoscopic Roux-en-Y gastric bypass (LRYGB) are the mainstays of bariatric surgery in recent years. In addition, there has been an increased interest in the quality of life (QoL) of obese patients after surgery. This study examined the QoL of patients who had undergone either LSG or LRYGB. We retrieved the literature from PubMed, Web of Science, Embase, and the Cochrane Library database before November 2019. A total of 10 articles and 2327 obese patients were included in our meta-analysis. The QoL scoring tools included in the statistical analysis are the following: the gastrointestinal quality of life index, 36-items short-form health survey, bariatric analysis and reporting outcome system, and the Moorehead-Ardelt quality of life questionnaire II. Although the QoL score of the LRYGB group was higher than that of the LSG group in the bariatric analysis and reporting outcome system subgroup, statistical analysis showed no difference in the postoperative QoL of LSG and LRYGB. In our study, no difference was found in the QoL between LSG and LRYGB. Therefore, in terms of postoperative QoL, surgical methods should be selected on the basis of the patients' condition and level of understanding of the surgeries.


Long-term Follow-up and Factors Associated with Active Surveillance Failure for Patients with Non-muscle-invasive Bladder Cancer: The Bladder Cancer Italian Active Surveillance (BIAS) Experience.
Active surveillance (AS) has been proposed as an alternative to transurethral resection (TUR) in selected patients with recurrent low-risk non-muscle-invasive bladder cancer (NMIBC). Here we report long-term results for patients on AS and investigate features associated with AS failure. Cases with recurrence after diagnosis of low-grade (LG) pTa/pT1a NMIBC were enrolled in the Bladder Italian Active Surveillance (BIAS) project. Over 251 AS events, we observed 130 failures (51.8%). In these patients, final pathology showed 25 benign lesions (19.2%) and 92 LG Ta (70.7%), 12 high-grade Ta/T1 (9.2%), and one T2 (0.7%) tumor. The treatment-free probability at 12, 18, 24, and 36 mo was 59.7%, 54.5%, 46.3%, and 40.4%, respectively. We identified 95 patients (37.8%) who remained on AS for >18 mo. A multivariable Cox regression model confirmed that patients with a history of multiple TURs (hazard ratio [HR] 1.59, 95% confidence interval [CI] 1.01-2.51) and those with more than one lesion at AS entry (HR 1.63, 95% CI 1.05-2.54) were significantly more likely to experience AS failure. Our results confirm that well-selected patients with NMIBC can safely remain on AS for a long period of time. Multiple TURs and multiple lesions at AS enrollment are associated with a higher risk of AS failure. PATIENT SUMMARY: Active surveillance has been proposed as an alternative to surgery for patients with recurrent low-risk superficial bladder cancer. Our report confirms that well-selected patients can safely avoid or postpone surgery.


The ULK3 kinase is a determinant of keratinocyte self-renewal and tumorigenesis targeting the arginine methylome.
Epigenetic mechanisms oversee epidermal homeostasis and oncogenesis. The identification of kinases controlling these processes has direct therapeutic implications. We show that ULK3 is a nuclear kinase with elevated expression levels in squamous cell carcinomas (SCCs) arising in multiple body sites, including skin and Head/Neck. ULK3 loss by gene silencing or deletion reduces proliferation and clonogenicity of human keratinocytes and SCC-derived cells and affects transcription impinging on stem cell-related and metabolism programs. Mechanistically, ULK3 directly binds and regulates the activity of two histone arginine methyltransferases, PRMT1 and PRMT5 (PRMT1/5), with ULK3 loss compromising PRMT1/5 chromatin association to specific genes and overall methylation of histone H4, a shared target of these enzymes. These findings are of translational significance, as downmodulating ULK3 by RNA interference or locked antisense nucleic acids (LNAs) blunts the proliferation and tumorigenic potential of SCC cells and promotes differentiation in two orthotopic models of skin cancer.


Conservative treatment in patients with an acute lumbosacral radicular syndrome: design of a randomised clinical trial [ISRCTN68857256].
The objective is to present the design of randomised clinical trial (RCT) on the effectiveness of physical therapy added to general practitioners management compared to general practitioners management only in patients with an acute lumbosacral radicular syndrome (also called sciatica). Patients in general practice diagnosed with an acute (less than 6 weeks) lumbosacral radicular syndrome and an age above 18 years are eligible for participation. The general practitioners treatment follows their clinical guideline. The physical therapy treatment will consist of patient education and exercise therapy. The primary outcome measure is patients reported global perceived effect. Secondary outcome measures are severity of complaints, functional status, health status, fear of movement, medical consumption, sickness absence, costs and treatment preference. The follow-up is 52 weeks. Treatment by general practitioners and physical therapists in this study will be transparent and not a complete "black box". The results of this trial will contribute to the decision of the general practitioner regarding referral to physical therapy in patients with an acute lumbosacral radicular syndrome.


Experimental lung transplantation: impact of preservation solution and route of delivery.
Optimal preservation of allograft integrity is essential to reduce post-ischemic organ dysfunction after lung transplantation. Retrograde organ preservation leads to homogeneous intrapulmonary distribution and eliminates intravascular thrombi. So far, no comparative studies exist with regard to preservation quality following retrograde preservation with Perfadex and Celsior after extended cold-ischemia intervals. In an in vivo pig model, 5 lungs each were preserved for 27 hours using antegrade or retrograde perfusion techniques with Celsior (Ce(ant)/CE(ret)) and Perfadex (PER(ant)/PER(ret)). After left lung transplantation and contralateral lung exclusion, hemodynamics, oxygenation and dynamic compliance were monitored for 6 hours and compared with sham-operated controls. Pulmonary edema was determined stereologically. Statistics consisted of analysis of variance (ANOVA) with repeated measures. Mortality of all Celsior-protected lungs was 100% due to severe reperfusion injury with profound lung edema. In contrast, organ preservation with PER(ant) led to sufficient graft function without mortality. Preservation quality after retrograde administration of Perfadex resulted in optimized oxygenation capacity compared with PER(ant) (p = 0.046). Furthermore, intra-alveolar edema was reduced and generally comparable with sham controls. In general, retrograde preservation led to continuous washout of small blood and fibrin clots from the pulmonary capillary system. Perfadex solution provided sufficient lung preservation for 27 hours of cold ischemia, and its retrograde application led to significant functional and histologic improvement compared with antegrade perfusion. In contrast, preservation with Celsior solution resulted in lethal post-ischemic outcome, regardless of the route of administration, and therefore must be considered unsuitable for extended lung procurement.


A classification and regression tree analysis identifies subgroups of childhood type 1 diabetes.
Diabetes in childhood and adolescence includes autoimmune and non-autoimmune forms with heterogeneity in clinical and biochemical presentations. An unresolved question is whether there are subtypes, endotypes, or theratypes within these forms of diabetes. The multivariable classification and regression tree (CART) analysis method was used to identify subgroups of diabetes with differing residual C-peptide levels in patients with newly diagnosed diabetes before 20 years of age (n=1192). The robustness of the model was assessed in a confirmation and prognosis cohort (n=2722). The analysis selected age, haemoglobin A1c (HbA1c), and body mass index (BMI) as split parameters that classified patients into seven islet autoantibody-positive and three autoantibody-negative groups. There were substantial differences in genetics, inflammatory markers, diabetes family history, lipids, 25-OH-Vitamin D3, insulin treatment, insulin sensitivity and insulin autoimmunity among the groups, and the method stratified patients with potentially different pathogeneses and prognoses. Interferon-ɣ and/or tumour necrosis factor inflammatory signatures were enriched in the youngest islet autoantibody-positive groups and in patients with the lowest C-peptide values, while higher BMI and type 2 diabetes characteristics were found in older patients. The prognostic relevance was demonstrated by persistent differences in HbA1c at 7 years median follow-up. This multivariable analysis revealed subgroups of young patients with diabetes that have potential pathogenetic and therapeutic relevance. The work was supported by funds from the German Federal Ministry of Education and Research (01KX1818; FKZ 01GI0805; DZD e.V.), the Innovative Medicine Initiative 2 Joint Undertaking INNODIA (grant agreement No. 115797), the German Robert Koch Institute, and the German Diabetes Association.


Response of compost maturity and microbial community composition to pentachlorophenol (PCP)-contaminated soil during composting.
Two composting piles were prepared by adding to a mixture of rice straw, vegetables and bran: (i) raw soil free from pentachlorophenol (PCP) contamination (pile A) and (ii) PCP-contaminated soil (pile B). It was shown by the results that compost maturity characterized by water soluble carbon (WSC), TOC/TN ratio, germination index (GI) and dehydrogenase activity (DA) was significantly affected by PCP exposure, which resulted in an inferior degree of maturity for pile B. DGGE analysis revealed an inhibited effect of PCP on compost microbial abundance. The bacteria community shifts were mainly consistent with composting factors such as temperature, pH, moisture content and substrates. By contrast, the fungal communities were more sensitive to PCP contamination due to the significant correlation between fungal community shifts and PCP removal. Therefore, the different microbial community compositions for properly evaluating the degree of maturity and PCP contamination were suggested.


Characterization of yeast cultivations by steric sedimentation field-flow fractionation.
The characterization and quantification of biomass is often time consuming and dependent on the cultivation media and gives no detailed information between cell size and shape and their productivity. By monitoring the bioprocess with steric sedimentation field-flow fractionation (Sd/StFFF) in combination with laser light scattering, not only cell growth, but also the variation of cell size and shape during the cultivation, can be observed. In this work, the feasibility of separating and characterizing cell populations by steric sedimentation field-flow fractionation is demonstrated by its application to three different yeast cultivation broths. For this purpose samples which were collected at different cultivation times were injected into an FFF system. Fractograms were obtained in less than 4 min. Due to the relatively high resolution of the method, a cell sample could be fractionated in several subpopulations differing in their size as well as in their number of buds.


Relevance of diagnostic investigations in patients with uveitis: Retrospective cohort study on 300 patients.
The diagnostic workup of uveitis is a challenge due to the wide range of diagnoses and the lack of a well-codified diagnostic procedure. We aimed to evaluate the relevance of diagnostic investigations for the etiological diagnosis of uveitis. Retrospective cohort study of patients referred for etiological diagnosis of uveitis. Uveitis related to ophthalmological diseases or occurring during the course of previously diagnosed diseases were not included. Three hundred patients were included. Chest CT-scan was suggestive of sarcoidosis in 83 (29%). Features associated with abnormal CT-scan were: snowballs and/or peripheral multifocal choroiditis (PMC) upon ocular examination (P=0.004), blood lymphopenia (P<0.0001), angiotensin converting enzyme (ACE) level>1.5 ULN (P=0.0003). Bronchoscopy showed granuloma in 18 (11%) while alveolar lymphocytosis suggestive of sarcoidosis was reported in 45 (27%). Presence of granuloma on bronchial biopsies was always associated with chest CT-scan abnormalities, whereas 31% of patients with alveolar lymphocytosis had normal CT-scans. Features associated with contributive bronchoscopy were: snowballs and/or PMC (P=0.003), ACE>1.5 ULN (P=0.007), abnormal chest-CT scan (P<0.0001). Salivary gland biopsy revealed granuloma in 12 patients (5%). Cerebral MRI was abnormal in 15 patients (9%) who mostly presented with snowballs and/or retinal vasculitis. Finally, the main causes of uveitis were latent tuberculosis (25%) and sarcoidosis (22%), but 34% remained of undetermined origin. Uveitis relapses were observed in 31% and did not differ between patients with an identified diagnosis and those with idiopathic uveitis. Identification of factors associated with abnormal investigations might improve the optimal diagnostic workup adapted to each patient.


Electroconvulsive therapy induces remodeling of hippocampal co-activation with the default mode network in patients with depression.
Electroconvulsive therapy (ECT) is a highly efficient treatment for depression. Previous studies repeatedly reported an ECT-induced volume increase in the hippocampi. We assume that this also affects extended hippocampal networks. This study aims to investigate the structural and functional interplay between hippocampi, hippocampal pathways and core regions of the default mode network (DMN). Twenty patients with a current depressive episode receiving ECT-treatment and twenty age and sex matched healthy controls (HC) were included in the study. ECT-patients underwent multimodal magnetic resonance imaging (MRI)-scans (diffusion weighted imaging, resting state functional MRI) before and after an ECT-index series. HC were also scanned twice in a similar between-scan time-interval. Parahippocampal cingulum (PHC) and uncinate fasciculus (UF) were reconstructed for each participant using manual tractography. Fractional anisotropy (FA) was averaged across tracts. Furthermore, we investigated seed-based functional connectivity (FC) from bilateral hippocampi and from the PCC, a core region of the DMN. At baseline, FA in PHC and UF did not differ between groups. There was no baseline group difference of hippocampal-FC. PCC-FC was decreased in ECT-patients. ECT induced a decrease in FA in the left PHC in the ECT group. No longitudinal changes of FA were found in the UF. Furthermore, there was a decrease in hippocampal-PCC-FC, an increase in hippocampal-supplementary motor area-FC, and an increase in PCC-FC in the ECT-group, reversing group differences at baseline. Our findings suggest that ECT induces structural and functional remodeling of a hippocampal-DMN. Those changes may contribute to ECT-induced clinical response in patients with depression.


The use of chiral lithium amides in the desymmetrisation of N-trialkylsilyl dimethyl sulfoximines.
Chiral base desymmetrisation of dimethyl sulfoximines could provide a general route to chiral, enantioenriched dialkyl sulfoximines with potential for use in asymmetric catalysis. Asymmetric deprotonation of N-trialkylsilyl dimethyl sulfoximines with either enantiomer of lithium N,N-bis(1-phenylethyl)amide in the presence of lithium chloride affords enantioenriched sulfoximines on electrophilic trapping. Ketones, ketimines, trialkylsilyl chlorides and activated alkyl halides may be used as electrophiles in the reaction. Furthermore, a modified Horner-Emmons methodology was investigated. Simple chiral lithium amides afford products with enantiomeric excesses of up to 70%, illustrating that chiral base desymmetrisation of dimethyl sulfoximines is possible.


Nursing issues: selection and analysis.
The authors describe the use of two strategies for selecting and analyzing issues. These systematic approaches provide a foundation not only for determining and studying issues, but also for implementing resolutions. Use of both processes makes dynamic, meaningful issues courses possible in nursing education.


Tumor-cell vaccination induces tumor dormancy in a murine model of B-cell leukemia/lymphoma (BCL1).
Immunity to murine B-cell leukemia/lymphoma (BCL1) induced by multiple injections with irradiated tumor cells, prevented leukemia development in primary and adoptive transfer recipients despite long-lasting persistence of residual tumor cells. Detection of dormant BCL1 cells was carried out by PCR analysis using the VH-rearranged DNA sequence as a BCL1 clonal marker. Dormant tumor cells were detected > 250 days following immunity induction in 40% of spleens from healthy immune mice having no detectable symptoms of disease. Tumor dormancy was not abrogated by adoptive transfer of BCL1-containing splenocytes into syngeneic recipients, indicating that cell-mediated anti-tumor immunity contributes to maintenance of the tumor dormant state and prevents renewed tumor-cell growth. Splenocytes but not sera from immune mice conferred specific radiosensitive protection from a lethal dose of BCL1 cells included in cell mixtures transferred to secondary recipients. A therapeutic effect of transferred immune splenocytes was shown in BCL1-bearing mice, which remained disease-free for > 200 days after inoculation; nevertheless, dormant BCL1 cells were detected by PCR analysis in some of the surviving mice. Our results suggest that an efficient tumor-cell vaccine can lead to induction of tumor dormancy that can be maintained by a cell-derived mechanism for a long period of time.


Intravenous fat tolerance. Correlation with very low density lipoprotein apoprotein B kinetics in man.
The intravenous fat tolerance test (IVFTT) has been introduced as a measure of the fractional catabolic rate of the endogenous triglyceride of plasma. To assess the validity of this test we have compared this test in 21 normal and hyperlipidaemic subjects with direct measurement of the fractional catabolic rate of autologous radio-iodinated VLDL. There was a strong positive correlation between the rate constant K2 of the IVFTT and the fractional catabolic rate of VLDL-apolipoprotein B (r=+0.87). The two rates were considerably different in magnitude. The IVFTT appears to be a valid index of the fractional catabolic rate of VLDL. Its limitations and uses are discussed.


Ultralarge anti-Stokes lasing through tandem upconversion.
Coherent ultraviolet light is important for applications in environmental and life sciences. However, direct ultraviolet lasing is constrained by the fabrication challenge and operation cost. Herein, we present a strategy for the indirect generation of deep-ultraviolet lasing through a tandem upconversion process. A core-shell-shell nanoparticle is developed to achieve deep-ultraviolet emission at 290 nm by excitation in the telecommunication wavelength range at 1550 nm. The ultralarge anti-Stokes shift of 1260 nm (~3.5 eV) stems from a tandem combination of distinct upconversion processes that are integrated into separate layers of the core-shell-shell structure. By incorporating the core-shell-shell nanoparticles as gain media into a toroid microcavity, single-mode lasing at 289.2 nm is realized by pumping at 1550 nm. As various optical components are readily available in the mature telecommunication industry, our findings provide a viable solution for constructing miniaturized short-wavelength lasers that are suitable for device applications.


Regional vulnerability for COVID-19 in Cameroon.
few studies have assessed risk for coronavirus disease 2019 (COVID-19) within African countries. Here we examine differences in vulnerability to COVID-19 among the ten administrative regions and two major cities of Cameroon based on epidemiological risk factors and access to healthcare resources. regional epidemiological and healthcare access vulnerability indices were created and compared with cumulative COVID-19 cases, case fatality rates, co-morbidities, and healthcare resources in Cameroon. based on epidemiological risk factors, populations in the East Region, Douala (in the Littoral Region), West Region, and Yaoundé (in the Center Region) are at highest risk for COVID-19. Meanwhile, the North, Far North, East, and Adamawa Regions had the most healthcare access vulnerability. COVID-19 cases per population were highest in the Center, Littoral, and East Regions. Case fatality rates were greatest in the North Region. Potential co-morbidities with greater prevalence among COVID-19 patients included male sex, hypertension, and diabetes. epidemiological risk factors for COVID-19 and access to healthcare varies between the regions of Cameroon. These discrepancies are potentially reflected in regional differences of COVID-19 cases and case fatality rates. In particular, the East Region has high epidemiological risk factors and low healthcare accessibility compared to other regions. Understanding the relationships between epidemiological risk factors, access to healthcare resources, and COVID-19 cases in Cameroon could aid decision-making among national policymakers and inform further research.


Loss of vision due to central serous chorioretinopathy following psychological stress.
The authors studied 33 patients with central serous chorioretinopathy and found that a very disturbing psychological event had preceded the loss of vision in 91% of the cases. The acute disturbance preceded the first visual symptoms by an average of 7 days. When relapses occurred, the psychological disturbances were often less severe and preceded the visual symptoms by minutes or hours. In some cases vision improved 1 to 2 weeks after the patient learned of the amelioration of the original distressing situation. The majority of the patients were found to be tension ridden, and 48% had cardiovascular abnormalities.


Monoamine oxidase inhibitors and the cheese effect.
The behavior of inhibitors of monoamine oxidase-A (MAO-A) is considered in terms of the possibility of having an effective antidepressant that does not give rise to hypertensive interactions with dietary tyramine. Studies with punch-biopsy samples of human intestine and rat intestinal samples show MAO-A to be the predominant form of the enzyme in both species. Transport studies with everted rat intestinal preparations indicate that tyramine is extensively metabolized during transport through the intestine. Selective inhibition of MAO-A by clorgyline results in a large increase in the amount of unchanged tyramine transported, whereas selective inhibition of MAO-B with L-deprenyl (selegiline) has no significant effect. The behavior of reversible MAO-A inhibitors can significantly reduce, but not entirely eliminate, these effects on the intestinal metabolism of tyramine, but only if the inhibition is competitive in nature.


Ambient anthropogenic noise but not light is associated with the ecophysiology of free-living songbird nestlings.
Urbanization is associated with dramatic increases in noise and light pollution, which affect animal behaviour, physiology and fitness. However, few studies have examined these stressors simultaneously. Moreover, effects of urbanization during early-life may be detrimental but are largely unknown. In developing great tits (Parus major), a frequently-used model species, we determined important indicators of immunity and physiological condition: plasma haptoglobin (Hp) and nitric oxide (NOx) concentration. We also determined fledging mass, an indicator for current health and survival. Associations of ambient noise and light exposure with these indicators were studied. Anthropogenic noise, light and their interaction were unrelated to fledging mass. Nestlings exposed to more noise showed higher plasma levels of Hp but not of NOx. Light was unrelated to Hp and NOx and did not interact with the effect of noise on nestlings' physiology. Increasing levels of Hp are potentially energy demanding and trade-offs could occur with life-history traits, such as survival. Effects of light pollution on nestlings of a cavity-nesting species appear to be limited. Nonetheless, our results suggest that the urban environment, through noise exposure, may entail important physiological costs for developing organisms.


2D Co-MOF nanosheet-based nanozyme with ultrahigh peroxidase catalytic activity for detection of biomolecules in human serum samples.
A two-dimensional (2D) Co-MOF nanosheet-based nanozyme was developed for colorimetric detection of disease-related biomolecules. The prepared 2D Co-MOFs exhibited ultrahigh peroxidase catalytic activity. 2D Co-MOFs can catalyze the oxidation of colorless 3,3',5,5'-tetramethylbenzidine (TMB) to the blue product oxTMB, accompanying an obvious change of absorption value at 652 nm. However, alkaline phosphatase can catalyze the hydrolysis of L-ascorbic acid-2-phosphate to produce ascorbic acid which can reduce the oxTMB to TMB, resulting in an obvious color fading. Therefore, by recording the change of absorption value at 652 nm, the 2D Co-MOF nanosheets were used to detect ascorbic acid (AA) and alkaline phosphatase (ALP). The limit of detection for AA and ALP was 0.47 μM and 0.33 U L-1, respectively. The limit of quantification for AA and ALP was 1.56 μM and 1.1 U L-1, respectively. The developed nanozyme was successfully used to determine alkaline phosphatase in clinical human serum samples and the results were consistent with those provided by the hospital. Furthermore, by integrating 2D Co-MOF nanosheets with image recognition and data processing function fixed on a smartphone, a portable test of ascorbic acid was reached. Schematic presentation of the preparation of two-dimensional Co-MOF nanosheet-based nanozyme and their application in portable detection of biomolecules.


Habituation of the auditory startle reaction is reduced during preparation for execution of a motor task in normal human subjects.
The generalized acoustic startle reaction is a useful but labile phenomenon that undergoes a relatively rapid habituation with repeated stimuli and can be modified by changes in the environmental context. In the present work, we examined the influence of the experimental set on size, latency and habituation rate of auditory startle reactions in 15 normal volunteers. Series of 5 acoustic startling stimuli were applied on each of the following 4 conditions: (1) at rest in a quiet and dull ambience; (2) at rest but engaged in a busy environment; (3) being prepared to execute a reaction time task; and (4) focussing the attention to an impending visual stimulus. We found that the amplitude of the response to the first stimulus was significantly larger in condition 1, and habituation rate was significantly reduced in condition 3, with respect to all other conditions. The enhancement of the startle reaction in a quiet ambience may result from reduction of the sensory inputs from the environment, which would otherwise act as prepulses and cause a certain degree of inhibition. The reduced habituation rate of the startle reaction with preparation for a reaction time task may be due to a transient block of the cortical inhibitory control on inputs from non-expected sensory afferents. A careful description of the experimental conditions with which the startle reactions are tested is required for meaningful comparison of the results from different laboratories. The possibility to reduce habituation of the startle reaction with preparedness for execution of a motor task has important implications with regard to the applicability of the startle reaction on research and clinical practice.


[Conventional roentgen functional diagnosis--videodensitometry. 1. Densitometric and topometric measurements of roentgen video images: technique and method of measuring].
It is possible to measure movements in the human body with the help of X-ray television systems. A great number of different techniques has been published in the scientific literature. They all based on only two principles with qualitative differences in signal acquisition. The densitometric and topometric measurements are assessed and compared. Neither the densitometric nor the topometric principle seems to be superior. To support the experimental work the videoanalyser VIANA MP was developed on the Ilmenau Institute of Technology.


Specific effects of ATP on the kinetics of reconstituted bovine heart cytochrome-c oxidase.
Bovine heart cytochrome-c oxidase was reconstituted in liposomes and the kinetics of cytochrome c oxidation were measured by the polarographic and photometric method under uncoupled conditions in the presence of various polyvalent anions. In order to distinguish between specific and unspecific ionic effects of ATP, the photolabelling reagent 8-azido-ATP was applied. Covalently bound ATP at the enzyme complex caused the same increase of Km for cytochrome c as free ATP, if measured by the photometric assay. The increase of Km by photolabelling with 8-azido-ATP was completely prevented by ATP, but not by ADP. The data indicate the occurrence of a specific binding site for ATP at the cytosolic side of cytochrome-c oxidase, which, after binding of ATP, changes the kinetics of cytochrome c oxidation.


The Serotonin-Immune Axis in Preeclampsia.
To review the literature and detail the potential immune mechanisms by which hyperserotonemia may drive pro-inflammation in preeclampsia and to provide insights into potential avenues for therapeutic discovery. Preeclampsia is a severe hypertensive complication of pregnancy associated with significant maternal and fetal risk. Though it lacks any effective treatment aside from delivery of the fetus and placenta, recent work suggests that targeting serotonin systems may be one effective therapeutic avenue. Serotonin dysregulation underlies multiple domains of physiologic dysfunction in preeclampsia, including vascular hyporeactivity and excess platelet aggregation. Broadly, serotonin is increased across maternal and placental domains, driven by decreased catabolism and increased availability of tryptophan precursor. Pro-inflammation, another hallmark of the disease, may drive hyperserotonemia in preeclampsia. Interactions between immunologic dysfunction and hyperserotonemia in preeclampsia depend on multiple mechanisms, which we discuss in the present review. These include altered immune cell, kynurenine pathway metabolism, and aberrant cytokine production mechanisms, which we detail. Future work may leverage animal and in vitro models to reveal serotonin targets in the context of preeclampsia's immune biology, and ultimately to mitigate vascular and platelet dysfunction in the disease. Hyperserotonemia in preeclampsia drives pro-inflammation via metabolic, immune cell, and cytokine-based mechanisms. These immune mechanisms may be targeted to treat vascular and platelet endophenotypes in preeclampsia.


Proteolytic cleavage of Beclin 1 exacerbates neurodegeneration.
Neuronal cell loss contributes to the pathology of acute and chronic neurodegenerative diseases, including Alzheimer's disease (AD). It remains crucial to identify molecular mechanisms sensitizing neurons to various insults and cell death. To date, the multifunctional, autophagy-related protein Beclin 1 has been shown to be both necessary and sufficient for neuronal integrity in neurodegenerative models associated with protein aggregation. Interestingly, besides its role in cellular homeostasis, Beclin 1 has also been ascribed a role in apoptosis. This makes it critical to elucidate whether Beclin 1 regulates neuronal death and survival across neurodegenerative conditions independent of protein clearance. Here, we provide experimental evidence for a direct functional link between proteolytic cleavage of Beclin 1 and apoptotic neuronal cell loss in two independent models of neurodegeneration in vivo. Proteolytic cleavage of Beclin 1 was characterized in lysates of human AD brain samples. We developed viral tools allowing for the selective neuronal expression of the various Beclin 1 forms, including Beclin 1 cleavage products as well as a cleavage-resistant form. The effect of these Beclin 1 forms on survival and integrity of neurons was examined in models of acute and chronic neurodegeneration in vitro and in vivo. Markers of neuronal integrity, neurodegeneration and inflammation were further assessed in a Kainic acid-based mouse model of acute excitotoxic neurodegeneration and in a hAPP-transgenic mouse model of AD following perturbation of Beclin 1 in the susceptible CA1 region of the hippocampus. We find a significant increase in caspase-mediated Beclin 1 cleavage fragments in brain lysates of human AD patients and mimic this phenotype in vivo using both an excitotoxic and hAPP-transgenic mouse model of neurodegeneration. Surprisingly, overexpression of the C-terminal cleavage-fragment exacerbated neurodegeneration in two distinct models of degeneration. Local inhibition of caspase activity ameliorated neurodegeneration after excitotoxic insult and prevented Beclin 1 cleavage. Furthermore, overexpression of a cleavage-resistant form of Beclin 1 in hippocampal neurons conferred neuroprotection against excitotoxic and Amyloid beta-associated insults in vivo. Together, these findings indicate that the cleavage state of Beclin 1 determines its functional involvement in both neurodegeneration and neuroprotection. Hence, manipulating the cleavage state of Beclin 1 may represent a therapeutic strategy for preventing neuronal cell loss across multiple forms of neurodegeneration.


A Posttranscriptional Pathway of CD40 Ligand mRNA Stability Is Required for the Development of an Optimal Humoral Immune Response.
CD40 ligand (CD40L) mRNA stability is dependent on an activation-induced pathway that is mediated by the binding complexes containing the multifunctional RNA-binding protein, polypyrimidine tract-binding protein 1 (PTBP1) to a 3' untranslated region of the transcript. To understand the relationship between regulated CD40L and the requirement for variegated expression during a T-dependent response, we engineered a mouse lacking the CD40L stability element (CD40LΔ5) and asked how this mutation altered multiple aspects of the humoral immunity. We found that CD40LΔ5 mice expressed CD40L at 60% wildtype levels, and lowered expression corresponded to significantly decreased levels of T-dependent Abs, loss of germinal center (GC) B cells and a disorganized GC structure. Gene expression analysis of B cells from CD40LΔ5 mice revealed that genes associated with cell cycle and DNA replication were significantly downregulated and genes linked to apoptosis upregulated. Importantly, somatic hypermutation was relatively unaffected although the number of cells expressing high-affinity Abs was greatly reduced. Additionally, a significant loss of plasmablasts and early memory B cell precursors as a percentage of total GL7+ B cells was observed, indicating that differentiation cues leading to the development of post-GC subsets was highly dependent on a threshold level of CD40L. Thus, regulated mRNA stability plays an integral role in the optimization of humoral immunity by allowing for a dynamic level of CD40L expression on CD4 T cells that results in the proliferation and differentiation of pre-GC and GC B cells into functional subsets.


[Association between serotonin 1D gene polymorphisms and attention deficit hyperactivity disorder comorbid or not comorbid learning disorder].
To investigate the relationship between two HTR1D gene polymorphisms, 1350T>C and 1236A>G polymorphisms, and attention deficit hyperactivity disorder (ADHD) comorbid or not comorbid learning disorder (LD). Blood samples were taken from 91 trios with probands of ADHD comorbid LD and 181 trios with probands of ADHD not comorbid LD. DNA was extracted. 1350T>C and 1236A>G were genotyped by restriction fragment length polymorphism analysis. Transmit/disequilibrium test and haplotype analysis were used to test the association between the two polymorphisms of HTR1D gene and ADHD comorbid or not comorbid LD separately. 1236A allele (chi2=5.306, P=0.021) was over transmitted to probands of ADHD without LD. No biased transmissions of any allele and haplotype were found in families with probands of ADHD with LD. whether ADHD comorbid LD or not comorbid LD makes difference at the level of HTR1D gene polymorphism of 1236A>G.


The investigation of a series of n-hydroxybenzoic acids (n=p, m, o) on a new surface enhanced Raman scattering active substrate.
Ag nanoparticles, organized on indium tin oxide (ITO) surface, can act as a new surface enhanced Raman scattering (SERS) active substrate as well as a dry electrode. Compared with the traditional SERS-active substrate, its notable advantage is that the microcosmic changes of the film can be reflected by the SERS spectrum during the investigation of the film's electrical and other macroscopic characteristics. To illuminate the above-mentioned property of this new substrate, a series of n-hydroxybenzoic acids (n-HBA; n=p, m and o) was tested as probe molecules by SERS technique. These SERS spectra indicate that the significant changes of frequencies as well as intensities, respectively, arise from the changes of the adsorption behavior along with the proportional variation of molecules and silver nanoparticles. Excellent SERS signals prove that the silver nanoparticles-coated ITO is a highly SERS-active substrate and can efficiently reflect the microcosmic property of the film, which suggest it has promising potential of being a new technique for further application in the field of thin-film research.


Baseline distribution and sources of selected agricultural runoff in the bottom water of an active cockle farming area, Bagan Pasir, Perak, Malaysia.
This paper aims to study the spatial and temporal patterns of selected agricultural runoff, specifically in terms of glyphosate, nitrate, and ammonia in bottom water, as well as their possible sources, within an active cockle farming area in Bagan Pasir, Perak, Malaysia. Samples were taken along the cockle farming area from March to November 2019. Glyphosate was analyzed using HPLC with both extraction and derivatization methods using 9-fluorenyl-methyl chloroformate (FMOC-Cl), while nitrate and ammonia levels were determined using the standard Hach method. Generally, glyphosate, nitrate, and ammonia were present within the study site with the average concentration of 37.44 ± 12.27 μg/l, 1.65 ± 0.52 mg/l, and 0.37 ± 0.19 mg/l, respectively. The results suggest that glyphosate and nitrate might be derived from an inland source, while a uniform and low level of ammonia suggested might originate from lithogenic origins. Continuous monitoring remains encouraged.


Male sexual behavior does not require elevated testosterone in a lizard (Coleonyx elegans, Eublepharidae).
Male sexual behavior depends on gonadal androgens in species of all major vertebrate lineages, including reptiles. However, male sexual behavior includes distinct appetitive and consummatory phases, typically denoted as courtship and mounting, with potentially different hormonal control. Different proximate controls of courtship versus mounting could enable disconnected evolutionary losses and gains of various aspects of male sexual behavior. Male courtship display, which is activated by testosterone (T) in many species, is an ancestral trait in the lizard family Eublepharidae. However, Coleonyx elegans (Yucatan Banded Gecko) lost the courtship display, while retaining a highly simplified male sexual behavior that involves only mounting for copulation. We performed surgical manipulations (castration with and without T replacement in adult males; implantation of adult females with exogenous T) to investigate hormonal mechanisms involved in this evolutionary novelty. Our results indicate that the expression of simplified sexual behavior in C. elegans does not require elevated circulating levels of T, a finding that is previously unreported in lizards. In females, however, exogenous T induced male-like mounting. Thus, the mounting phase of sexual behavior is not activated by T in the traditional sense of this term but probably requires post-natal, maturational organization (if not periodic reorganization) by androgens. We conclude that the simplification of male sexual behavior and its independence from elevated levels of circulating androgens in C. elegans evolved via 1) evolutionary loss of the androgen-activated courtship display and 2) retention of the mounting phase, which has a longer "functional memory" for the effects of androgenic steroids.


Diffusion MR imaging: an important tool in the assessment of brain tumors.
For over 20 years, conventional MR imaging has been used for assessing brain tumors. However, conventional MR imaging tends to underestimate the extent of the tumor, perhaps leading to suboptimal treatment. New MR imaging tools have been widely used to determine the grade, heterogeneity, and extent of brain tumors. Diffusion-weighted imaging has been studied extensively, helping in tumor grading, differential diagnosis, and postoperative evaluation. Diffusion tensor imaging can apparently delineate more accurately the tumor versus the infiltrating tumor between the peritumoral edema and the normal brain parenchyma. This article shows the main clinical applications of these sequences.


Exploring the predictors of health-protective behavior during the COVID-19 pandemic: A multi-country comparison.
In recent years, examining the determinants of health behaviors on a multi-country level remains limited. Therefore, the purpose of this study is to explore the key factors that may enhance the adoption of health-protective behaviors during the COVID-19 pandemic in Morocco and India. A theoretical framework derived from the health belief model (HBM) was used for this research. Data was collected from a sample of 444 adult individuals split across Morocco (n = 215) and India (n = 229). Data analysis was carried out using two-stage multiple-analytic techniques. First, structural equation modeling (SEM) was employed to test the hypothesized relationships. Second, an artificial neural network (ANN) model was employed to rank the significant independent variables obtained from SEM analysis. The results of SEM showed that perceived benefit is the key predictor of the protective behavior in Morocco, followed by self-efficacy, and then perceived severity. By contrast, ANN analysis showed that perceived severity was the most vital factor for predicting the protective behavior in Morocco, followed by perceived benefits, and then self-efficacy. For the Indian sample, both SEM analysis and the ANN model revealed that the impact of perceived susceptibility on the adoption of the protective measure is stronger than that of cues to action. Theoretical contributions and managerial implications are also discussed toward the end.


A review of technical progression in the robot-assisted radical prostatectomy.
Since the advent of the robotic surgery, its implementation in urology has been both wide and rapid. Particularly in extirpative surgery for prostate cancer, techniques in robotic-assisted radical prostatectomy have-and continue to-evolve to maximize functional and oncologic outcomes. In this review, we briefly present a historical perspective of the evolution of various robotic techniques, allowing us to contextualize contemporary robotic approaches to radical prostatectomy.


Safety and tolerability of non-neutralizing adrenomedullin antibody adrecizumab (HAM8101) in septic shock patients: the AdrenOSS-2 phase 2a biomarker-guided trial.
Investigate safety and tolerability of adrecizumab, a humanized monoclonal adrenomedullin antibody, in septic shock patients with high adrenomedullin. Phase-2a, double-blind, randomized, placebo-controlled biomarker-guided trial with a single infusion of adrecizumab (2 or 4 mg/kg b.w.) compared to placebo. Patients with adrenomedullin above 70 pg/mL, < 12 h of vasopressor start for septic shock were eligible. Randomization was 1:1:2. Primary safety (90-day mortality, treatment emergent adverse events (TEAE)) and tolerability (drug interruption, hemodynamics) endpoints were recorded. Efficacy endpoints included the Sepsis Support Index (SSI, reflecting ventilator- and shock-free days alive), change in Sequential-related Organ Failure Assessment (SOFA) and 28-day mortality. 301 patients were enrolled (median time of 8.5 h after vasopressor start). Adrecizumab was well tolerated (one interruption, no hemodynamic alteration) with no differences in frequency and severity in TEAEs between treatment arms (TEAE of grade 3 or higher: 70.5% in the adrecizumab group and 71.1% in the placebo group) nor in 90-day mortality. Difference in change in SSI between adrecizumab and placebo was 0.72 (CI -1.93-0.49, p = 0.24). Among various secondary endpoints, delta SOFA score (defined as maximum versus minimum SOFA) was more pronounced in the adrecizumab combined group compared to placebo [difference at 0.76 (95% CI 0.18-1.35); p = 0.007]. 28-day mortality in the adrecizumab group was 23.9% and 27.7% in placebo with a hazard ratio of 0.84 (95% confidence interval 0.53-1.31, log-rank p = 0.44). Overall, we successfully completed a randomized trial evaluating selecting patients for enrolment who had a disease-related biomarker. There were no overt signals of harm with using two doses of the adrenomedullin antibody adrecizumab; however, further randomized controlled trials are required to confirm efficacy and safety of this agent in septic shock patients.


Prevalence and Associated Factors of Age-Related Macular Degeneration in a Russian Population: The Ural Eye and Medical Study.
To assess the prevalence of age-related macular degeneration (AMD) in a Russian population. Population-based prevalence assessment. The Ural Eye and Medical Study was conducted in a rural and urban area in the Russian republic of Bashkortostan. The study included 5,899 participants aged 40+ years old. AMD, defined according to the Beckman Initiative for Macular Research, was assessed by fundus photographs and optical coherence tomographic images of 4,932 (83.6%) participants. The prevalence of any AMD, early AMD, intermediate AMD, or late AMD, geographic atrophy, and neovascular AMD were 18.2% (95% confidence interval [CI], 16.8-19.6), 11.6% (95% CI, 10.4-12.8), 5.0% (95% CI, 4.2-5.8), 1.6% (95% CI, 1.1-2.0), 0.7% (95% CI, 0.4-1.0) and 0.9% (95% CI, 0.6-1.3), respectively, for individuals >55 years old. Applying an age limit of 40+ years for the AMD definition, prevalence of any AMD, early AMD, intermediate AMD, late AMD, geographic atrophy and neovascular AMD were 14.1% (95% CI, 13.1-15.1), 9.4% (95% CI, 8.6-10.2), 3.8% (95% CI, 3.2-4.3), 1.0% (95% CI, 0.7-1.2), 0.4% (95% CI, 0.2-0.6) and 0.5% (95% CI, 0.3-0.7), respectively, for individuals aged 40+ years. Higher AMD prevalence was correlated with older age (odds ratio [OR], 1.15; 95% CI, 1.13-1.16; P < 0.001), rural region (OR, 1.69; 95% CI, 1.32-2.17; P < 0.001), lower diabetes prevalence (OR, 0.56; 95% CI, 0.38-0.82; P = 0.003), and shorter axial length (OR, 0.89; 95% CI, 0.79-0.99; P = 0.04). AMD prevalence was not significantly (all P ≥ 0.20) correlated with any systemic parameter examined, except for lower prevalence of diabetes. In this typical, ethnically mixed, urban and rural population from Russia, a higher prevalence for AMD was associated mainly with older age, rural region of habitation, shorter axial length, and lower prevalence of diabetes mellitus. The AMD prevalence was lower than in Europeans and higher than in East Asians.


Contrasting effects of peroxisome-proliferator-activated receptor (PPAR)gamma agonists on membrane-associated prostaglandin E2 synthase-1 in IL-1beta-stimulated rat chondrocytes: evidence for PPARgamma-independent inhibition by 15-deoxy-Delta12,14prostaglandin J2.
Microsomal prostaglandin E synthase (mPGES)-1 is a newly identified inducible enzyme of the arachidonic acid cascade with a key function in prostaglandin (PG)E2 synthesis. We investigated the kinetics of inducible cyclo-oxygenase (COX)-2 and mPGES-1 expression with respect to the production of 6-keto-PGF1alpha and PGE2 in rat chondrocytes stimulated with 10 ng/ml IL-1beta, and compared their modulation by peroxisome-proliferator-activated receptor (PPAR)gamma agonists. Real-time PCR analysis showed that IL-1beta induced COX-2 expression maximally (37-fold) at 12 hours and mPGES-1 expression maximally (68-fold) at 24 hours. Levels of 6-keto-PGF1alpha and PGE2 peaked 24 hours after stimulation with IL-1beta; the induction of PGE2 was greater (11-fold versus 70-fold, respectively). The cyclopentenone 15-deoxy-Delta12,14prostaglandin J2 (15d-PGJ2) decreased prostaglandin synthesis in a dose-dependent manner (0.1 to 10 microM), with more potency on PGE2 level than on 6-keto-PGF1alpha level (-90% versus -66% at 10 microM). A high dose of 15d-PGJ2 partly decreased COX-2 expression but decreased mPGES-1 expression almost completely at both the mRNA and protein levels. Rosiglitazone was poorly effective on these parameters even at 10 microM. Inhibitory effects of 10 microM 15d-PGJ2 were neither reduced by PPARgamma blockade with GW-9662 nor enhanced by PPARgamma overexpression, supporting a PPARgamma-independent mechanism. EMSA and TransAM analyses demonstrated that mutated IkappaBalpha almost completely suppressed the stimulating effect of IL-1beta on mPGES-1 expression and PGE2 production, whereas 15d-PGJ2 inhibited NF-kappaB transactivation. These data demonstrate the following in IL-1-stimulated rat chondrocytes: first, mPGES-1 is rate limiting for PGE2 synthesis; second, activation of the prostaglandin cascade requires NF-kappaB activation; third, 15d-PGJ2 strongly inhibits the synthesis of prostaglandins, in contrast with rosiglitazone; fourth, inhibition by 15d-PGJ2 occurs independently of PPARgamma through inhibition of the NF-kappaB pathway; fifth, mPGES-1 is the main target of 15d-PGJ2.


Interinstitutional clinical practice guidelines for the treatment of acute myocardial infarction.
Mexico has the highest 30-day mortality due to acute myocardial infarction (AMI), which constitutes one of the main causes of mortality in the country: 28 % versus 7.5 % on average for the Organization for Economic Co-operation and Development member countries. To establish critical pathways and essential interinstitutional pharmacological strategies for the care of patients with AMI in Mexico, regardless of their socioeconomic status. A group of experts in AMI diagnosis and treatment, representatives of the main public health institutions in Mexico, as well as the Mexican cardiology societies, the Mexican Red Cross and representatives of the Spanish Society of Cardiology, were brought together in order to optimize strategies based on the best existing evidence. An interinstitutional clinical practice guideline was designed for early diagnosis and timely treatment of AMI with ST-segment elevation, following the clinical horizon of the disease, with the proposal of algorithms that improve the prognosis of patients who attend the emergency services due to an AMI. With these clinical practice guidelines, the group of experts proposes to universalize AMI diagnosis and treatment, regardless of patient socioeconomic status. México tiene la mortalidad más alta a 30 días por infarto agudo de miocardio (IAM), el cual constituye una de las principales causas de mortalidad en el país: 28 % versus 7.5 % del promedio de los países de la Organización para la Cooperación y el Desarrollo Económicos. Establecer las rutas críticas y las estrategias farmacológicas esenciales interinstitucionales para la atención de los pacientes con IAM en México, independientemente de su condición socioeconómica. Se reunió a un grupo de expertos en diagnóstico y tratamiento de IAM, representantes de las principales instituciones públicas de salud de México, así como las sociedades cardiológicas mexicanas, Cruz Roja Mexicana y representantes de la Sociedad Española de Cardiología con la finalidad de optimizar las estrategias con base en la mejor evidencia existente. Se diseñó una guía de práctica clínica interinstitucional para el diagnóstico temprano y tratamiento oportuno del IAM con elevación del segmento ST, siguiendo el horizonte clínico de la enfermedad, con la propuesta de algoritmos que mejoren el pronóstico de los pacientes que acuden por IAM a los servicios de urgencias. Con la presente guía práctica, el grupo de expertos propone universalizar el diagnóstico y tratamiento en el IAM, independientemente de la condición socioeconómica del paciente.


Review article: medical, surgical and radiological management of perianal Crohn's fistulas.
Crohn's anal fistulas are common and cause considerable morbidity. Their management is often difficult; medical and surgical treatments rarely lead to true healing with frequent recurrence and complications. To examine medical treatments previously and currently used, surgical techniques and the important role of optimal imaging. We conducted a literature search in the Pub Med database using Crohn's, Anal Fistula, Surgery, Imaging and Medical Treatment as search terms. Antibiotics and immunosuppressants have a role, but slow initial response, side effects and relatively low remission rates of up to around a third with frequent recurrence limit their value. Long-term infliximab produces clinical remission in 36-58% of patients with combined medical and surgical management achieving optimal outcomes. Traditional and newer surgical procedures often have a high rate of recurrence with a significant risk of temporary or, in up to 10% of cases, permanent stomas, incontinence and unhealed or slowly healing wounds in 30%. Management of Crohn's anal fistulas remains challenging. Established principles are to drain infection, use setons as required, aggressively manage active proctitis, give antibiotics, immunosuppressants and employ anti-TNFα therapy, and they demand significant co-operation between gastroenterologists and surgeons.


Determination of aromatic amine mutagens, PBTA-1 and PBTA-2, in river water by solid-phase extraction followed by liquid chromatography-tandem mass spectrometry.
We describe a novel method for the determination of two kinds of aromatic amine mutagens, 2-[2-(acetylamino)-4-[bis(2-methoxyethyl)-amino]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-1) and 2-[2-(acetylamino)-4-[bis(2-cyanoethyl)-ethylamino]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-2), in river water based on liquid chromatography-electrospray ionization-tandem mass spectrometry (LC-ESI-MS-MS). A solid-phase extraction procedure was used for the extraction of PBTA-1 and PBTA-2 from river water. The procedure was rapid and the relative standard deviations were below 4%. The detection limits of PBTA-1 and PBTA-2 in river water using the proposed method were found to be 1 and 2 ng/l, respectively. The compounds were detected by this method in river water taken from two sites in the Yodo River system at the ng/l level.


Role of conserved F(alpha)-helix residues in the native fold and stability of the kinase-inhibited oxy state of the oxygen-sensing FixL protein from Sinorhizobium meliloti.
The oxygen-sensing FixL protein from Sinorhizobium meliloti is part of the heme-PAS family of gas sensors that regulate many important signal transduction pathways in a wide variety of organisms. We examined the role of the conserved F(alpha)-9 arginine 200 and several other conserved residues on the proximal F(alpha)-helix in the heme domain of SmFixL* using site-directed mutagenesis in conjunction with UV-visible, EPR, and resonance Raman spectroscopy. The F(alpha)-helix variants R200A, E, Q, H, Y197A, and D195A were expressed at reasonable levels and purified to homogeneity. The R200I and Y201A variants did not express in observable quantities. Tyrosine 201 is crucial for forming the native protein fold of SmFixL* while Y197 and R200 are important for stabilizing the kinase-inhibited oxy state. Our results show a clear correlation between H-bond donor ability of the F(alpha)-9 side chain and the rate of heme autoxidation. This trend in conjunction with crystal structures of liganded BjFixL heme domains, show that H-bonding between the conserved F(alpha)-9 arginine and the heme-6-propionate group contributes to the kinetic stability of the kinase-inactivated, oxy state of SmFixL*.


Laser-structured superhydrophobic/superoleophilic aluminum surfaces for efficient oil/water separation.
The current demand for oil/water separation with an efficient, cost-effective, and environmentally friendly method is increasing. A laser-structured superhydrophobic/superoleophilic aluminum was prepared by using a nanosecond laser. The aluminum plate was used for oil/water separation without external force, which can replace the traditional porous materials. The effect of hole diameter and spacing on the effectiveness of oil/water separation is discussed. The results show that the aluminum plate with a hole size of 0.5 mm can be considered a more appropriate choice for the oil/water mixtures with large water content. In addition, complete separation of oil and water can be achieved in the hole spacing range of 1.0-3.0 mm. The oil separation speed can be increased without changing the water permeability by reducing the hole spacing, which is positively related to the hole spacing. Separation efficiencies were tested with various oil/water mixtures. The aluminum plate with a hole size of 0.5 mm can quickly separate the different oil mixtures with less than 50% oil content while achieving an oil separation efficiency of up to 99%. Due to the difference in dynamic viscosity of various oil phases, the separation efficiencies of the petrol, kerosene, and diesel are slightly different but can still be maintained above 99%. The laser-processed aluminum plate has several advantages of high porosity, high surface of superhydrophobic properties, and easy tunable structures. In practical applications, the hole size and the spacing should be appropriately adjusted according to specific conditions, such as different oils, the mixing ratios, etc., to obtain the best separation efficiency and speed.


[Evolution rules and clinical value of apparent diffusion coefficient in cerebral infarction].
To determine the rules that apparent diffusion coefficient (ADC) changes with time and space in cerebral infarction, and to provide the evidence in defining the stage, guiding treatment or judging the prognosis in infarction. Eighty-eight work-ups in 69 patients with cerebral infarction (8 hyperacute, 35 acute, 20 subacute, and 25 chronic infarctions) were imaged with both conventional MRI and diffusion weighted imaging. The average ADC, the average relative ADC (rADC), and the ADC or rADC from the center to the periphery of the lesion were calculated. The average ADC and the average rADC of hyperacute and acute infarction lesion depressed obviously. The average ADC and the average rADC of subacute infarction lesion were significantly higher than those of hyperacute and acute infarction lesion (P < 0.05), and some approached the values of uninjured side which appeared "pseudonormal values" at 10 to 14 days. The average ADC and the average rADC in chronic infarction lesion were the highest (P < 0.05). The longer the prognosis, the higher the average ADC and the average rADC of infarction lesion. The ADC and the rADC in 7 hyperacute and 26 acute lesions had gradient signs that these lesions increased from the center to the periphery. The ADC and the rADC in 15 subacute lesions had adverse gradient signs that these lesions decreased from the center to the periphery. The ADC and the rADC of infarction lesions have evolution rules with time and space corresponding to the pathophysiological foundation. The evolution rules with time and those in space can be helpful to decide the clinical stage and pathophysiological phase of infarction, and to provide the evidence in guiding the treatment or judging the prognosis in infarction.


Biological mesh for abdominal wall hernia synthetic mesh multidrug-resistant Pseudomonas aeruginosa infection: report of a case.
The use of biological mesh for the treatment of synthetic mesh-related infections in patients who undergo ventral hernia repair has been considered over the past few years. Removal of the infected synthetic mesh, which may be required in such cases, can result in recurring herniation. Biological implants have thus been recently used for the reconstruction of the existing defect. We herein present the case of a patient who developed multidrug-resistant Pseudomonas aeruginosa synthetic mesh infection following hernia repair, which was managed by the removal of the material and the application of a biological mesh in the contaminated area.


PAHs and metals in the soils of inner-city and suburban New Orleans, Louisiana, USA.
Representative soil samples of an inner-city and suburban community (n = 19 each) are evaluated for 16 polycyclic aromatic hydrocarbons-PAHs (naphthalene, acenaphthylene, acenaphthene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, benz(a)anthracene, chrysene, benzo[k]fluoranthene, benzo[j]fluoranthene, benzo(a)pyrene, indeno[1,2,3-cd]pyrene, dibenz[a,h]anthracene and benzo[g,h,i]perylene) and nine metals (Pb, Zn, Cd, Mn, Ni, Cu, Cr, Co and V). Surface (2.5cm deep) samples were air-dried and sieved (2mm USGS #10). Accelerated solvent extraction was used for PAH preparation prior to analysis with gas chromatography-mass spectrometry. Metals were extracted at a 5:1 ratio of 1mol nitric acid to soil, shaken at room temperature, centrifuged, filtered and analyzed by inductively coupled plasma-atomic emission spectrometry (ICP-AES). Total PAHs (median 2927ngg(-1) versus 731ngg(-1)) and the total metals (median 1323μgg(-1) versus 183μgg(-1)) summarize differences (P < 0.0001) between the inner-city and suburb, respectively. A strong association exists between PAHs and metals for all 38 soil samples (correlation coefficient = 0.831, P < 0.00001). In terms of the specific sites of accumulation, both PAHs and metals show the same pattern: busy streets > foundations > residential streets > open areas. This study provides real-world data about various chemical mixtures which may be a factor of possible health disparities in sensitive populations, especially children, in different communities of New Orleans.