Vasopressin and methylprednisolone and hemodynamics after in-hospital cardiac arrest - A post hoc analysis of the VAM-IHCA trial.
The Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA) trial demonstrated a significant improvement in return of spontaneous circulation (ROSC) with no clear effect on long-term outcomes. The objective of the current manuscript was to evaluate the hemodynamic effects of intra-cardiac arrest vasopressin and methylprednisolone during the first 24 hours after ROSC. The VAM-IHCA trial randomized patients with in-hospital cardiac arrest to a combination of vasopressin and methylprednisolone or placebo during the cardiac arrest. This study is a post hoc analysis focused on the hemodynamic effects of the intervention after ROSC. Post-ROSC data on the administration of glucocorticoids, mean arterial blood pressure, heart rate, blood gases, vasopressor and inotropic therapy, and sedation were collected. Total vasopressor dose between the two groups was calculated based on noradrenaline-equivalent doses for adrenaline, phenylephrine, terlipressin, and vasopressin. The present study included all 186 patients who achieved ROSC in the VAM IHCA-trial of which 100 patients received vasopressin and methylprednisolone and 86 received placebo. The number of patients receiving glucocorticoids during the first 24 hours was 22/86 (26%) in the placebo group and 14/100 (14%) in the methylprednisolone group with no difference in the cumulative hydrocortisone-equivalent dose. There was no significant difference between the groups in the mean cumulative noradrenaline-equivalent dose (vasopressin and methylprednisolone: 603 ug/kg [95CI% 227; 979] vs. placebo: 651 ug/kg [95CI% 296; 1007], mean difference -48 ug/kg [95CI% -140; 42.9], p = 0.30), mean arterial blood pressure, or lactate levels. There was no difference between groups in arterial blood gas values and vital signs. Treatment with vasopressin and methylprednisolone during cardiac arrest caused no difference in mean arterial blood pressure, vasopressor use, or arterial blood gases within the first 24 hours after ROSC when compared to placebo.


Development of highly stable ICG-polymeric nanoparticles with ultra-high entrapment efficiency using supercritical antisolvent (SAS)-combined solution casting process.
Indocyanine green (ICG), a water-soluble near-infrared (NIR) photosensitizer, has been enormously regarded in tumor diagnosis and phototherapy. Although tremendous progress in establishing the nanocarrier-based delivery systems has been explored, several limitations of low ICG encapsulation and sophisticated fabrication process remain significant challenges in producing nanoplatforms, limiting the theranostic outcomes of ICG. According to the unique advantages of the supercritical antisolvent (SAS) process and solution casting method, a novel combination approach to obtain the ICG-loaded nanoparticles (ICG-PLO NPs) is demonstrated, in which SAS assisted-ICG nanoparticles (ICG NPs) are coated with polypeptide poly-l-ornithine (PLO) using solution casting approach. This unique nanoplatform with ultra-high drug encapsulation efficiency remarkably improved the aqueous and photothermal stability of ICG. Notably, the coating of PLO could improve the internalization level in cells and anticancer effect in vivo, comprehensively augmenting the cancer phototherapy effect of ICG. Together, the findings of novel particle formation by integrated strategy would certainly broaden the applications of supercritical fluid (SCF) technology, potentiating the design of nano-formulations of ICG for clinical translation.


Adiposity and Coagulation: Predicting Postinjury Coagulation With Advanced Imaging Analysis.
Anatomic distribution of adipose tissue has demonstrated variable associations with hypercoagulability. Utilizing a retrospective analysis of a previously enrolled prospective cohort, we assessed computed tomography (CT) scan-based anthropometric and volumetric measures of adiposity as predictors of postinjury hypercoagulability. Segmentation analysis of arrival CT scans in significantly injured patients at a single level-I trauma center enrolled from December 2017 to August 2021 were analyzed for anthropometric indices of waist circumference (WC) and sagittal abdominal diameter (SAD), and volumetric parameters of visceral adipose tissue, superficial/deep subcutaneous adipose tissue, psoas/paravertebral muscle volume, and abdominal wall muscle volume. Associations with thromboelastography (TEG) were explored. Data from 91 patients showed strong correlations between body mass index and standard anthropometric measures of WC and SAD (P < 0.001); calculated volumes of subcutaneous adipose tissue and visceral adipose tissue (P < 0.001); and ratios of subcutaneous adipose:psoas muscle (SP ratio) and visceral adipose:psoas muscle ratio (both with P < 0.001, respectively). Correlation between TEG maximal amplitude (MA) and body mass index and SAD were not significant, with only weak correlation between TEG-MA and WC (r = 0.238, P = 0.041). Moderate but significant correlations existed between SP ratio and TEG-MA (r = 0.340, P = 0.005), but not visceral adipose:psoas muscle ratio (r = 0.159, P = 0.198). The relationship between TEG-MA and SP ratio remained significant when adjusted for injury severity score and lactate level (b = 0.302, P = 0.001). SP ratio is more strongly correlated with TEG-MA than standard obesity measures, and independently predicts increasing clot strength/stability after injury. Coagulation-relevant measures of sarcopenic obesity can be measured on CT scan, and may be used to optimize thromboprophylaxis strategies for obese injured patients.


Concentration-dependent effects of tungstate on germination, growth, lignification-related enzymes, antioxidants, and reactive oxygen species in broccoli (Brassica oleracea var. italica L.).
The phyto-impact of tungstate is not frequently studied like other heavy metals especially in the sight of continuous accumulation of tungstate in the agriculture soils and water. Thus, the present study was aimed to investigate the supplementation of various tungstate concentrations (0, 1, 5, 10, 50, and 100) to germination water (mg L-1) or clay soil (mg kg-1) on germination and metabolism of broccoli. Lower concentrations (1-10 mg L-1) accelerated germination process and reciprocally were recorded at the highest one (100 mg L-1). The promoter effect of lower concentrations on seedlings growing on tungstate contaminated soil was underpinned from enhancement of pigments, metabolites, enzymatic and non-enzymatic antioxidants, and nitrate reductase. However, the highest concentration-noxious impacts perceived from oxidative damage and membrane integrity deregulation accompanied with no gain from increment of proline, superoxide dismutase, and glutathione-S-transferase. The depletion of phytochelatins and nitric oxide jointed with the enhancement of peroxidases, polyphenol oxidase, and phenylalanine ammonia-lyase at higher concentration reinforced lignin production which restricted plant growth. The results supported the hormetic effects of tungstate (beneficial at low concentrations and noxious at high concentration) on morphological and physiological parameters of broccoli seedlings. The stimulatory effect of tungstate on metabolic activities could serve as important components of antioxidative defense mechanism against tungstate toxicity.


Local factor analysis of rank-deficient reaction systems.
The analysis of spectral measurement data sets using local factor analysis (LFA) requires the rank of the sub-matrix under study to be equal to the number of absorbing species present in the associated sub-system. However, because of mass balance or kinetic constraints, LFA will fail if local rank deficiency occurs. A local rank deficiency sub-system may be present in a global full-rank reaction system or a rank-deficient one. In this paper, the problems occurring when using window target-testing factor analysis (WTTFA), one type of the LFA methods, in a local rank-deficient situation are shown. A new augmented WTTFA (AWTTFA) is then proposed for the correct use of WTTFA when rank deficiency occurs. Principles of this new method have been demonstrated by a simulated kinetic system and an industrial batch data set.


Expression of Id1 in adult, regenerating and developing pancreas.
Several key transcription factors are necessary for alpha cell development in the pancreas. In this study, we describe the expression of Inhibition of DNA-binding protein 1 (Id1) in the developing as well as the normal adult pancreas. We found co-expression of Id1 with bone morphogenetic protein (BMP) receptor in alpha cells. Inhibition of BMP4 signaling with a specific neutralizing antibody slightly decreases the proportion of glucagon cells in the adult pancreas but had a significant effect in a model of pancreas regeneration. In late embryonic pancreas, Id1 co-localized with GATA4, a transcription factor known for its critical function in glucagon cell development. However, in early postnatal period, the expression of Id1 and GATA4 diverged with Id1 identified in glucagon cells and GATA4 restricted to the acinar pancreas.


[Transgenerational transmission of radiation-induced genomic instability and predisposition to carcinogenesis].
The paper deals with a history of radiobiological investigations carried out at the Center since 1925 which have contributed to the present-day conception on the influence of damaged DNA on stochastic (carcinogenesis) and non-stochastic (accelerated aging) late radiation pathology in exposed biological objects. A phenomenological and pathogenetic similarity of somatic (in irradiated organisms) and genetic (in progeny of irradiated parents) consequences of exposure to ionizing radiation is suggested and our data are presented pointing to a possibility of germ cells of irradiated parents to transmit genomic instability to the progeny thus increasing risk of carcinogenesis.


Effect of pre-eclampsia on plasma cholinesterase activity.
Plasma cholinesterase (PCHE) activity was determined using a colorimetric method in 11 healthy non-pregnant women, 11 healthy pregnant women at term, and 11 pre-eclamptic pregnant women at term. The mean plasma cholinesterase activities for healthy non-pregnant women, healthy pregnant women and pre-eclamptic pregnant women were 438 +/- 81,257 +/- 25 and 173 +/- 18 units . ml-1, respectively. Our data suggest that there is a significant reduction in plasma cholinesterase activity in preeclamptic pregnant women when compared to healthy non-pregnant (p less than 0.001) and healthy pregnant women (p less than 0.001).


Digital transformation of health and care to sustain Planetary Health: The MASK proof-of-concept for airway diseases-POLLAR symposium under the auspices of Finland's Presidency of the EU, 2019 and MACVIA-France, Global Alliance against Chronic Respiratory Diseases (GARD, WH0) demonstration project, Reference Site Collaborative Network of the European Innovation Partnership on Active and Healthy Ageing.
In December 2019, a conference entitled "Europe That Protects: Safeguarding Our Planet, Safeguarding Our Health" was held in Helsinki. It was co-organized by the Finnish Institute for Health and Welfare, the Finnish Environment Institute and the European Commission, under the auspices of Finland's Presidency of the EU. As a side event, a symposium organized as the final POLLAR (Impact of air POLLution on Asthma and Rhinitis) meeting explored the digital transformation of health and care to sustain planetary health in airway diseases. The Finnish Allergy Programme collaborates with MASK (Mobile Airways Sentinel NetworK) and can be considered as a proof-of-concept to impact Planetary Health. The Good Practice of DG Santé (The Directorate-General for Health and Food Safety) on digitally-enabled, patient-centred care pathways is in line with the objectives of the Finnish Allergy Programme. The ARIACARE-Digital network has been deployed in 25 countries. It represents an example of the digital cross-border exchange of real-world data and experience with the aim to improve patient care. The integration of information technology tools for climate, weather, air pollution and aerobiology in mobile Health applications will enable the development of an alert system. Citizens will thus be informed about personal environmental threats, which may also be linked to indicators of Planetary Health and sustainability. The digital transformation of the public health policy was also proposed, following the experience of the Agency for Health Quality and Assessment of Catalonia (AQuAS).


Unilateral pigmented paravenous retinochoroidal atrophy with acute angle-closure glaucoma: a case report.
Pigmented paravenous retinochoroidal atrophy (PPRCA) is an uncommon fundus disease characterized by perivenous aggregations of pigment clumps and retinochoroidal atrophy distributed along the retinal veins. We report a Chinese female case of unilateral PPRCA with acute angle-closure glaucoma (AACG). A 50-year-old Chinese female presented with vision loss and elevated intraocular pressure (IOP) in the right eye and then underwent trabeculectomy. She referred to our clinic for further evaluation and treatment. The funduscopic examination revealed grayish retinochoroidal atrophy and osteocyte-like pigment clumping lesions along the retinal veins and peripapillary preretinal hemorrhage in the right eye. The patient also presented with AACG in the same eye on the basis of past medical history of acute attack, shallow anterior chamber depth (ACD), narrow angle showed by ultrasound biomicroscopy (UBM) and glaucomatous neuropathy identified by optical coherence tomography (OCT). Other examinations like fluorescein fundus angiography (FFA), electroretinogram (ERG) and electrooculography (EOG) all confirmed the aforementioned diagnose. PPRCA is a rare disease, uncommon in females and symmetrical in both eyes. We present a rare case of unilateral PPRCA accompanied with AACG.


A Call to Restore Your Calling: Self-Care of the Emergency Physician in the Face of Life-Changing Stress-Part 4 of 6: Physician Helplessness and Moral Injury.
Many aspects of our health care system in the United States can lead to physicians feeling helpless-an inability to save a dying child, an inability to protect an immunocompromised child from a vaccine-preventable illness because of waning herd immunity, and a burdensome new electronic medical record system that your employer insists you must use. The cumulative effect of these experiences can lead to moral distress and ultimately moral injury. We discuss helplessness, moral distress, and moral injury in the setting of today's practice of emergency medicine and provide concrete recommendations to help providers cope with their own reactions to distressing clinical situations.


Elucidating prognosis and biology of breast cancer arising in young women using gene expression profiling.
Breast cancer in young women is associated with poor prognosis. We aimed to define the role of gene expression signatures in predicting prognosis in young women and to understand biological differences according to age. Patients were assigned to molecular subtypes [estrogen receptor (ER)(+)/HER2(-); HER2(+), ER(-)/HER2(-))] using a three-gene classifier. We evaluated whether previously published proliferation, stroma, and immune-related gene signatures added prognostic information to Adjuvant! online and tested their interaction with age in a Cox model for relapse-free survival (RFS). Furthermore, we evaluated the association between candidate age-related genes or gene sets with age in an adjusted linear regression model. A total of 3,522 patients (20 data sets) were eligible. Patients aged 40 years or less had a higher proportion of ER(-)/HER2(-) tumors (P < 0.0001) and were associated with poorer RFS after adjustment for breast cancer subtype, tumor size, nodal status, and histologic grade and stratification for data set and treatment modality (HR = 1.34, 95% CI = 1.10-1.63, P = 0.004). The proliferation gene signatures showed no significant interaction with age in ER(+)/HER2(-) tumors after adjustment for Adjuvant! online. Further analyses suggested that breast cancer in the young is enriched with processes related to immature mammary epithelial cells (luminal progenitors, mammary stem, c-kit, RANKL) and growth factor signaling in two independent cohorts (n = 1,188 and 2,334). Proliferation-related prognostic gene signatures can aid treatment decision-making for young women. However, breast cancer arising at a young age seems to be biologically distinct beyond subtype distribution. Separate therapeutic approaches such as targeting RANKL or mammary stem cells could therefore be needed.


Effects of single and multiple treatments with L-dihydroxyphenylalanine (L-DOPA) on dopamine receptor-G protein interactions and supersensitive immediate early gene responses in striata of rats after reserpine treatment or with unilateral nigrostriatal lesions.
We studied effects of L-dihydroxyphenylalanine (L-DOPA) treatment in rats following reserpine treatment or unilateral 6-hydroxydopamine (6-OHDA) injections into medial forebrain bundle. Quantitative in situ hybridization for mRNA's coding for the zinc finger immediate early gene (IEG) zif/268 or Jun family IEG jun b revealed that single L-DOPA injections accentuated IEG expression 3- to 7-fold in the dopamine (DA)-depleted striatum. This increased IEG response did not derive from any alterations in DA receptor-G protein coupling, assayed by DA stimulation of 35S-guanosine-5' (gamma-thio) triphosphate (35S-GTP-gamma-S) binding to striatal sections. Reserpine treatment increased both basal and maximal striatal DA-stimulated 35S-GTP-gamma-S binding. The augmented IEG responses to single L-DOPA treatments involved dependency on both D1 and D2 receptors and acutely to N-methyl-D-aspartate (NMDA) channels. Repetitive L-DOPA treatments yielded persistently elevated (zif/268) or additionally up-regulated (jun b) IEG response in the denervated striatum and down-regulated IEG responses in the control striatum. Degraded L-DOPA responses and appearance of involuntary movements after chronic L-DOPA use in advanced Parkinson's disease may derive from these IEG changes.


Tuning of photoreceptor function in three mantis shrimp species that inhabit a range of depths. I. Visual pigments.
Visual pigments in many animal species, including stomatopod crustaceans, are adapted to the photic environments inhabited by that species. However, some species occupy a diversity of environments as adults (such as a range of depths in the ocean), and a single set of visual pigments would not be equally adaptive for all habitats in which individuals live. We characterized the visual pigment complements of three species of stomatopod crustaceans, Haptosquilla trispinosa, Gonodactylellus affinis, and Gonodactylopsis spongicola, which are unusual for this group in that each lives at depths from the subtidal to several tens of meters. Using microspectrophotometry, we determined the visual pigments in all classes of main rhabdoms in individuals of each species from shallow or deep habitats. Each species expressed the typical diversity of visual pigments commonly found in stomatopods, but there was little or no evidence of differential expression of visual pigments in animals of any species collected from different depths. Vision in these species, therefore, is not tuned to spectral characteristics of the photic environment by varying the assemblages of visual pigments appearing in their retinas.


Differential expression of galanin in the cholinergic basal forebrain of patients with Lewy body disorders.
Depletion of cholinergic neurons within the nucleus basalis of Meynert (nbM) is thought to contribute to the development of cognitive impairments in both Alzheimer's disease (AD) and Lewy body disorders (LBD). It has been reported that, in late stage AD, a network of fibres that contain the neuropeptide galanin displays significant hypertrophy and 'hyperinnervates' the surviving cholinergic neurons. Galanin is considered as a highly inducible neuroprotective factor and in AD this is assumed to be part of a protective tissue response. The aim of this study was to determine if a similar galanin upregulation is present in the nbM in post-mortem tissue from patients with LBD. Gallatin immunohistochemistry was carried out on anterior nbM sections from 76 LBD cases (27 PD, 15 PD with mild cognitive impairment (MCI), 34 PD with dementia (PDD) and 4 aged-matched controls. Galaninergic innervation of cholinergic neurons was assessed on a semi-quantitative scale. The LBD group had significantly higher galaninergic innervation scores (p = 0.016) compared to controls. However, this difference was due to increased innervation density only in a subgroup of LBD cases and this correlated positively with choline acetyltransferase-immunopositive neuron density. Galanin upregulation within the basal forebrain cholinergic system in LBD, similar to that seen in AD, may represent an intrinsic adaptive response to neurodegeneration that is consistent with its proposed roles in neurogenesis and neuroprotection.


Drug-induced liver injury associated with HIV medications.
Antiretroviral therapy (ART) for HIV infection frequently has been associated with elevated liver enzyme levels. Determining the cause of elevated liver enzyme levels in patients who have HIV is difficult because ART usually consists of three different drugs, patients may be taking additional hepatotoxic medications and patients who have HIV often suffer from other liver diseases. Several agents, however, are recognized as having noteworthy and specific patterns of toxicity. This article reviews the different HIV drug classes, incidence of elevated liver enzyme values by class and by individual drug, risk factors, specific toxicities, and possible mechanisms of injury.


Barriers to effective communication between veterans with chronic kidney disease and their healthcare providers.
Many patients with chronic kidney disease (CKD) have insufficient knowledge about CKD, which is associated with poorer health outcomes. Effective patient-provider communication can improve CKD patients' knowledge, thereby augmenting their participation in self-care practices. However, barriers to addressing CKD patients' information needs have not been previously characterized. Adults with an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m(2) or on chronic dialysis or with a kidney transplant were recruited from a Department of Veterans Affairs (VA) nephrology clinic. Semi-structured telephone interviews were conducted to assess patients' CKD information needs and demographic characteristics. A qualitative approach was used to analyze interview transcripts and identify themes pertaining to communication dynamics. Thirty-two patients participated. The mean age of participants was 63 years; most were male (94%) and non-Hispanic white (53%). CKD severity groups represented included CKD-3 (eGFR 30-59 mL/min/1.73 m(2); 34%), CKD-4 (eGFR 15-29 mL/min/1.73 m(2); 25%), CKD-5 (eGFR <15 mL/min/1.73 m(2); 16%), end-stage kidney disease on dialysis (13%) and kidney transplant recipients (12%). Several key themes emerged about barriers to patient-provider communication based on patients' reported care at both VA and non-VA facilities, including patients perceived their role as a 'listener', reported limited CKD knowledge, did not understand physicians' explanations and were dissatisfied with the patient-provider relationship. Several barriers to patient-provider communication prevent patients from meeting their information needs and perpetuate patient passivity. Future research should evaluate whether interventions that empower CKD patients to actively participate in their care increase knowledge and improve health outcomes.


A proposed mechanism for the observed ontogenetic improvement in the hearing ability of hapuka (Polyprion oxygeneios).
Swim bladder extensions and hearing ability were examined in the temperate reef fish Polyprion oxygeneios (hapuka). Using the auditory evoked potential (AEP) technique, hearing thresholds were determined in four age-classes of hapuka, from larvae to juveniles. The youngest age-class had poor hearing abilities, with lowest thresholds of 132 dB re 1 μPa, and a narrow auditory bandwidth (100-800 Hz). Hearing ability improved significantly throughout the remainder of their first year, including decreases in thresholds of up to 27 dB, and an increase in auditory bandwidth (up to 1,000 Hz). Magnetic resonance imaging (MRI) was used to investigate structural mechanisms that may account for this ontogenetic improvement in hearing. These showed rostral extensions of the swim bladder developing early in the juvenile stage, and extending with increasing age closer to the otic capsule. It is suggested that this indirect connection between the swim bladder and the otic capsule could impart pressure sensitivity closer to the inner ear, accounting for the increase in sensitivity seen during development, although further investigation of older fish is required for conclusive evidence. The improvement in hearing ability in hapuka could be potentially related to a unique life history of extended pelagic durations up to 4 years.


Porous tip radiofrequency ablation catheter reduced heart failure-related complications and healthcare resource utilization in paroxysmal atrial fibrillation patients.
A 56-hole porous tip radiofrequency catheter was developed to provide more uniform cooling with less fluid delivery than a prior 6-hole irrigated design. This study aimed to evaluate the impact of contact force (CF) ablation with the porous tip on complications (congestive heart failure [CHF] and non-CHF related), healthcare resource utilization, and procedural efficiency in patients undergoing de novo paroxysmal atrial fibrillation (PAF) ablations in a real-world setting. Consecutive de novo PAF ablations were performed between February 2014 and March 2019 by six operators at a single US academic center. The 6-hole design was used through December 2016 with the 56-hole porous tip adopted in October 2016. The outcomes of interest included symptomatic CHF presentation and CHF-related complications. Of 174 patients who were included, mean age was 61.1 ± 10.8 years, 67.8% were male, and 25.3% had a history of CHF. Ablation with the porous tip catheter significantly decreased fluid delivery (1177 vs. 1912 mL with the 6-hole design; p < .0001). CHF-related complications within 7 days, particularly fluid overload, were substantially reduced with the porous tip (15.2% vs. 5.3% of patients; p = .0281) and the proportion of patients with symptomatic CHF presentation within 30 days postablation was significantly lower (14.7% vs. 32.5%; p = .0058). The 56-hole porous tip led to significantly reduced CHF-related complications and healthcare utilization in PAF patients undergoing CF catheter ablation when compared to the prior 6-hole design. This reduction likely results from the significant decrease in fluid delivery during the procedure.


Viruses of Helminthosporium (Cochlioblus) victoriae.
The enigma of the transmissible disease of Helminthosporium victoriae has almost been resolved. Diseased isolates are doubly infected with two distinct viruses, the victorivirus Helminthosporium victoriae virus 190S and the chrysovirus HvV145S. Mixed infection, however, is not required for disease development. DNA transformation experiments and transfection assays using purified HvV190S virions strongly indicate that HvV190S alone is necessary for inducing disease symptoms. HvV145, like other chrysoviruses, appears to have no effect on colony morphology. This chapter will discuss the molecular biology of the two viruses and summarize recent results of characterization of host gene products upregulated by virus infection. Furthermore, the novel structural features of HvV190S capsid will be highlighted.


Disaster process-based spatiotemporal characteristics of apricot frost in the warm temperate zone (WTZ), China.
Frost stress is a major environmental factor that limits apricot growth in the warm temperate zone (WTZ) of China, and is always triggered by extreme low temperature weather processes. In this study, the characteristics of the apricot frost processes f(D, Tcum), which were identified from historical disaster representation, were analyzed and apricot frost evaluation indicators were developed, thus facilitating the process-based assessment and spatiotemporal analysis of apricot frost processes. Periods of low temperature that persist for 1~2, 3, and ≥4 days (i.e., duration days, D) provide the initial identification indicator for light, moderate, and severe apricot frost. The threshold ranges for Tcum are 0~3.9, 9.2~12.0, and >16.2 for D values of 1~2, 3, and ≥4, respectively. The northwest of the WTZ is dominated by apricot frost, with approximately 80% of apricot frost being light, followed by moderate and severe. Regional apricot frost exhibited a significant decreasing trend over the last four decades. A total of 29.65% of stations, which were mainly located in the northwest and middle parts of the study region, detected an increasing trend in apricot frost. The results provide technical support for targeted apricot frost level detection, and the process-based spatiotemporal characteristics of apricot frost can provide basic information for the prevention and mitigation of apricot frost.


Calcineurin inhibitors recruit protein kinases JAK2 and JNK, TLR signaling and the UPR to activate NF-κB-mediated inflammatory responses in kidney tubular cells.
The calcineurin inhibitors (CNIs) cyclosporine (CsA) and tacrolimus are key drugs in current immunosuppressive regimes for solid organ transplantation. However, they are nephrotoxic and promote death and profibrotic responses in tubular cells. Moreover, renal inflammation is observed in CNI nephrotoxicity but the mechanisms are poorly understood. We have now studied molecular pathways leading to inflammation elicited by the CNIs in cultured and kidney tubular cells. Both CsA and tacrolimus elicited a proinflammatory response in tubular cells as evidenced by a transcriptomics approach. Transcriptomics also suggested several potential pathways leading to expression of proinflammatory genes. Validation and functional studies disclosed that in tubular cells, CNIs activated protein kinases such as the JAK2/STAT3 and TAK1/JNK/AP-1 pathways, TLR4/Myd88/IRAK signaling and the Unfolded Protein Response (UPR) to promote NF-κB activation and proinflammatory gene expression. CNIs also activated an Nrf2/HO-1-dependent compensatory response and the Nrf2 activator sulforaphane inhibited JAK2 and JNK activation and inflammation. A murine model of CsA nephrotoxicity corroborated activation of the proinflammatory pathways identified in cell cultures. Human CNIs nephrotoxicity was also associated with NF-κB, STAT3 and IRE1α activation. In conclusion, CNIs recruit several intracellular pathways leading to previously non-described proinflammatory actions in renal tubular cells. Identification of these pathways provides novel clues for therapeutic intervention to limit CNIs nephrotoxicity.


Alterations of selected genes of the Wnt signal chain in rat kidneys with spontaneous congenital obstructive uropathy.
To determine the role of the Wnt signal cascade in the pathophysiology of congenital obstructive uropathy in rats, we assessed the expression patterns of selected genes. Total cellular mRNA of complete obstructed, contralateral and healthy control kidneys of rats with hereditary, spontaneous congenital hydronephrosis at the age of 14 and 32days was extracted and pooled. mRNA expression was assessed by real-time reverse transcription-polymerase chain reaction. Significant (P<0.05) differences in gene expression levels of obstructed versus contralateral and control kidneys were evaluated. In 14-day-old animals, Wnt-4 expression was decreased. Secreted frizzled-related protein (sFRP-1, sFRP-2), beta-catenin and Jun N-terminal kinase (JNK) expression was increased. The gene expression of Wnt-7b, Friz-1, Friz-2, calcineurin and Wnt inhibitory factor-1 (WIF-1) was unaltered. In 32-day-old animals, Wnt-4, Wnt-7b, Friz-2, sFRP-1 and WIF-1 expression was increased, whereas levels of Friz-1, sFRP-2, beta-catenin, JNK and calcineurin were unaltered. The results suggest an age-dependent role of Wnts in the pathophysiology of congenital renal obstruction in rats. Down-regulated Wnt signalling at the end of nephrogenesis in 14-day-old rats might indicate impaired tubulogenesis. Up-regulation of beta-catenin and JNK points to stressed cell-cell adhesion due to progressive hydronephrosis. Increased Wnt signalling in older animals probably contributes to interstitial fibrosis and tubular apoptosis. This study should be considered as a starting point to correlate in detail the observed alterations in gene expression with the pathophysiology of congenital obstructive uropathy.


Amyloid- and FDG-PET imaging in amyotrophic lateral sclerosis.
We aimed to study brain metabolism and presence of beta-amyloid deposits using positron emission tomography (PET) in patients with amyotrophic lateral sclerosis (ALS). This prospective cross-sectional study included 18 patients with definite or probable ALS according to the revised El Escorial diagnostic criteria, and 24 healthy controls. Patients underwent neurological and neuropsychological assessments, PET with (18)F-fluorodeoxyglucose (FDG), and amyloid-PET with (18)F-florbetaben. Patients with ALS showed hypometabolism in the frontal area and hypermetabolism in the cerebellum compared to healthy controls. Four patients (22 %) displayed cognitive impairment and decreased metabolism in the frontal area extending bilaterally to the parietal regions, and increased metabolism in the posterior area of the cerebellum. In patients with no cognitive impairment, metabolism was lower in the left superior frontal gyrus and higher in the anterior and posterior lobes of the cerebellum. In the individual analysis, six patients (35 %) displayed more anterior involvement with hypometabolism affecting the superior frontal, medial, and inferior gyri; six patients (35 %) exhibited a more posterior pattern with hypometabolism in the precentral and postcentral gyri and in the superior and inferior parietal lobules; two patients (11 %) showed a mixed pattern; and three patients (17 %) showed no alterations in brain metabolism. Three (16 %) showed increased (18)F-florbetaben uptake compared to controls. We have identified two main patterns of brain metabolism with an association to cognitive status. Only a subgroup of patients showed an increased uptake of the amyloid tracer. Our results suggest that ALS is heterogeneous from a clinical, metabolic, and molecular standpoint.


The effect of raloxifene and tibolone on the uterine blood flow and endometrial thickness: a transvaginal Doppler study.
To evaluate and compare the effect of different than classical hormone therapy medications, such as raloxifene and tibolone, on the uterine arteries and endometrium of postmenopausal women using transvaginal ultrasonography. The prospective study included 62 healthy, postmenopausal women recruited from the Menopausal Clinic of the 2nd Department of Obstetrics and Gynecology of the University of Athens. Subjects were randomly allocated to receive raloxifene HCl in a daily dose of 60 mg orally (Group A-31 women) or tibolone in a daily dose of 2.5 mg orally (Group B-31 women). The study period was 6 months and all subjects were assessed using transvaginal ultrasonography before treatment initiation as well as after 3 and 6 months for evaluation of the endometrial thickness and the pulsatility (PI) and resistance (RI) indices at the level of the uterine arteries. No significant differences in RI, PI and endometrial thickness were observed in the raloxifene group during the 6-month treatment. In the tibolone group, PI and RI values decreased linearly from baseline to the end of the study, whereas the endometrial thickness was significantly increased during the first 3 months remaining unaltered thereafter. Comparisons between the two study groups revealed significant percent change of values in the pre-treatment to month-3 period and no difference with regard to pre-treatment, month-3 and month-6 absolute values. Raloxifene and tibolone exert dissimilar effects on uterine blood supply parameters and endometrial thickness.


4-Hydroxy-7-oxo-5-heptenoic acid lactone can induce mitochondrial dysfunction in retinal pigmented epithelial cells.
Oxidation of docosahexaenoate (DHA)-containing phospholipids in the cell plasma membrane leads to release of the α,β-unsaturated aldehyde 4-hydroxy-7-oxo-5-heptenoic acid (HOHA) lactone which is capable of inducing retinal pigmented epithelial (RPE) cell dysfunction. Previously, HOHA lactone was shown to induce apoptosis and angiogenesis, and to activate the alternative complement pathway. RPE cells metabolize HOHA lactone through enzymatic conjugation with glutathione (GSH). Competing with this process is the adduction of HOHA lactone to protein lysyl residues generating 2-(ω-carboxyethyl)pyrrole (CEP) derivatives that have pathological relevance to age-related macular degeneration (AMD). We now find that HOHA lactone induces mitochondrial dysfunction. It decreases ATP levels, mitochondrial membrane potentials, enzymatic activities of mitochondrial complexes, depletes GSH and induces oxidative stress in RPE cells. The present study confirmed that pyridoxamine and other primary amines, which have been shown to scavenge γ-ketoaldehydes formed by carbohydrate or lipid peroxidation, are ineffective for scavenging the α,β-unsaturated aldehydes. Histidyl hydrazide (HH), that has both hydrazide and imidazole nucleophile functionalities, is an effective scavenger of HOHA lactone and it protects ARPE-19 cells against HOHA lactone-induced cytotoxicity. The HH α-amino group is not essential for this electrophile trapping activity. The Nα-acyl L-histidyl hydrazide derivatives with 2- to 7-carbon acyl groups with increasing lipophilicities are capable of maintaining the effectiveness of HH in protecting ARPE-19 cells against HOHA lactone toxicity, which potentially has therapeutic utility for treatment of age related eye diseases.


CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer.
Cancer-associated fibroblasts (CAFs) are one of the most significant components in the tumour microenvironment (TME), where they can perform several protumourigenic functions. Several studies have recently reported that CAFs are more heterogenous and plastic than was previously thought. As such, there has been a shift in the field to study CAF subpopulations and the emergent functions of these subsets in tumourigenesis. In this review, we explore how different aspects of CAF heterogeneity are defined and how these manifest in multiple cancers, with a focus on pancreatic ductal adenocarcinoma (PDAC). We also discuss therapeutic approaches to selectively target protumourigenic CAF functions, while avoiding normal fibroblasts, providing insight into the future of stromal targeting for the treatment of PDAC and other solid tumours.


The Role of Polygenic Score and Cognitive Activity in Cognitive Functioning Among Older Adults.
This study explored whether the intensity of cognitive activities could moderate the relationship between a genetic predisposition for developing Alzheimer's disease (AD) and cognitive functioning among older adults in the United States. Furthermore, we examined whether the same moderating effects were dependent on different measures of cognition. We used a data set from the 2000-2014 waves of the Health and Retirement Study and the Consumption and Activities Mail Survey. Our sample included 3,793 individuals aged 50 or older. We used the polygenic score (PGS) for AD as a genetic trait for cognitive functioning. Reading, listening to music, using a computer, playing cards/games/solving puzzles, singing/playing musical instruments, and creating art and crafts were included as cognitive activities, and TV viewing as passive activities. We used total cognition, fluid intelligence, and crystallized intelligence as proxies for cognitive functioning. Growth-curve models were conducted. After controlling for covariates, we found that reading books, using a computer, and playing cards/games/solving puzzles had a positive effect on cognitive functioning. An additional hour spent reading books moderated the negative effect of AD PGS on cognition. The measure of fluid, when compared with crystallized intelligence, appeared to drive these results. Reading could be a protective factor against cognitive decline among older adults who are genetically predisposed to developing AD. Implications for individuals, caregivers, clinicians, and policymakers are suggested. Furthermore, the onset of AD in those at greater genetic risk may be delayed with this intervention.


Synthetic semicrystalline cellulose oligomers as efficient Pickering emulsion stabilizers.
Nanocellulose are promising Pickering emulsion stabilizers for being sustainable and non-toxic. In this work, semicrystalline cellulose oligomers (SCCO), which were synthesized from maltodextrin using cellobiose as primer by in vitro enzymatic biosystem, were exploited as stabilizers for oil-in-water Pickering emulsions. At first, the morphology, structure, thermal and rheological properties of SCCO suspensions were characterized, showing that SCCO had a sheet morphology and typical cellulose-Ⅱ structure with 56 % crystallinity. Then the kinetic stabilities of emulsions containing various amounts of SCCO were evaluated against external stress such as pH, ionic strength, and temperature. Noting that SCCO-Pickering emulsions exhibited excellent stabilities against changes in centrifugation, pH, ionic strengths, and temperatures, and it was also kinetically stable for up to 6 months. Both SCCO suspensions and their emulsions exhibited gel-like structures and shear-thinning behaviors. These results demonstrated great potential of SCCO to be applied as nanocellulosic emulsifiers in food, cosmetic and pharmaceutical industries.


A silver stain for the detection of nanogram amounts of tRNA following two-dimensional electrophoresis.
Three ultrasensitive protein silver-staining methods have been compared with respect to the detection of tRNA in polyacrylamide gels. The method of Sammons (D. W. Sammons, L.D. Adams, and E.E. Nishizawa (1981) Electrophoresis 2, 135-141) has been shown to have remarkable sensitivity, with a detection limit of 0.3 ng tRNA/mm2, allowing the two-dimensional fractionation of submicrogram amounts of bulk tRNA. The application of this technique to developmental and differentiation problems and other areas where the amounts of nonradioactive tRNA available are limited is anticipated.


Mitochondrial biogenesis and apoptosis as underlying mechanisms involved in the cardioprotective effects of Gallic acid against D-galactose-induced aging.
Aging is a main risk factor for the development of cardiovascular diseases (CVDs). Gallic acid (GA) is a phenolic compound derived from a wide range of fruits. GA has a wide spectrum of pharmacological properties, including anti-oxidative, anti-inflammatory, and cardioprotective effects. This research was conducted to determine the cardioprotective effect of GA on cardiac hypertrophy in aged rats. Following histological evaluation and through observing the heart, we found that GA improved the cardiac hypertrophy induced by D-galactose (D-GAL) in cardiac cells. To clarify the causes for this anti-aging effect, we evaluated the malonic dialdehyde levels and antioxidant enzyme activity in rat cardiac tissue. The levels of lactate dehydrogenase (LDH) and creatine kinase (CK-MB) in serum were measured. The levels of genes related to mitochondrial biogenesis, mitophagy, and apoptosis in cardiac tissue were surveyed. The findings represented that GA ameliorated antioxidant enzyme activity while significantly decreasing the malonic dialdehyde levels. Real-time PCR analysis proposed that GA effectively improved mitochondrial biogenesis in the heart via regulating the expression levels of Sirtuin 1 (SIRT1), PPARγ coactivator 1α (PGC1-α), nuclear factor erythroid 2-related factor 2 (Nrf2), and mitochondrial transcription factor A (TFAM). GA also mitigated apoptosis in the heart by modulating the expression levels of B-cell lymphoma protein 2 (Bcl-2) and Bcl-2-associated X (Bax). In addition, GA improved serum LDH and CK-MB levels. GA may alleviate aging-induced cardiac hypertrophy via anti-oxidative, mitoprotective, and anti-apoptotic mechanisms.


Application of pier waste sludge for catalytic activation of proxy-monosulfate and phenol elimination from a petrochemical wastewater.
This investigation aimed to remove phenol from real wastewater (taken from a petrochemical company) by activating peroxy-monosulfate (PMS) using catalysts extracted from pier waste sludge. The physical and chemical properties of the catalyst were evaluated by FE-SEM/EDS, XRD, FTIR, and TGA/DTG tests. The functional groups of O-H, C-H, CO32-, C-H, C-O, N-H, and C-N were identified on the catalyst surface. Also, the crystallinity of the catalyst before and after reaction with petrochemical wastewater was 103.4 nm and 55.8 nm, respectively. Operational parameters of pH (3-9), catalyst dose (0-100 mg/L), phenol concentration (50-250 mg/L), and PMS concentration (0-250 mg/L) were tested to remove phenol. The highest phenol removal rate (94%) was obtained at pH=3, catalyst dose of 80 mg/L, phenol concentration of 50 mg/L, PMS concentration of 150 mg/L, and contact time of 150 min. Phenol decomposition in petrochemical wastewater followed the first-order kinetics (k> 0.008 min-1, R2> 0.94). Changes in pH factor were very effective on phenol removal efficiency, and maximum efficiency (≈83%) was achieved in pH 3. The catalyst stability test was performed for up to five cycles, and phenol removal in the fifth cycle was reduced to 42%. Also, the energy consumption in this study was 77.69 kW h/m3. According to the results, the pier waste sludge catalyst/PMS system is a critical process for eliminating phenol from petrochemical wastewater.


Effects of road traffic noise on the prevalence of cardiovascular diseases: The case of Thessaloniki, Greece.
Road traffic noise is a growing challenge for human health in the last decades. World Health Organization (WHO) summarized the scientific evidence on side effects of noise on public health and wellbeing since 1999 in its publication "Guidelines for community noise". The WHO's documentation was completed in 2009 with the Night Noise Guidelines for Europe and in 2011 with the Burden of disease from environmental noise highlighting the negative effects of environmental noise on health. In this paper, we studied and presented the overall noise levels and the exposure of the population in the city of Thessaloniki, Greece. The estimation of the exposure to road traffic noise was based on the census data for a 15-year time period (e.g. 2000-2015). The quantification of the environmental burden of cardiovascular diseases, due to urban traffic noise, is calculated in terms of DALYs. The calculation is based on the morbidity and mortality data from the hypertensive, ischemic heart, and cerebrovascular diseases of the total population. Our analysis proved that the road traffic noise in Thessaloniki causes almost 2000 DALYs lost in the total population each year. Also, the exposure to road traffic noise was estimated by three measuring points, two of them located in the urban Thessaloniki (a high traffic highway and a residential area) and the third one situated in one urban background area in the urban outskirts of Thessaloniki. The noise levels were measured for a 24-h period during a 3 year time period for every measuring point. The imposed WHO noise levels were exceeded in both high traffic highway and residential areas for almost the whole time of the measurement period.


An Analysis of Conflicts Across Role 1 Guidelines.
Role 1 care is vital to patient survival and includes many echelons of care from point-of-injury first aid to medical attention at battalion aid stations. Many guidelines are written for Role 1 care providers to optimize care for different scenarios. Differences in the guidelines lead to confusion and discrepancies between the types of treatment medical care providers provide. Although the guidelines were written for different areas of care, uniformity between the guidelines is needed and will lead to a reduced mortality rate. It was determined that the Tactical Combat Casualty Care Guidelines, Prolonged Field Care Guidelines, Joint Trauma System Clinical Practice Guidelines, and Standard Medical Operating Guidelines from medical evacuation were the military medical guidelines most relevant to Role 1 care. These Guidelines were compared side by side to determine the differences between them. Although the guidelines were largely similar, many major differences were found between them. Our online tables contain large inconsistences between guidelines including direct contradictions in conversion of junctional tourniquets and the administration of tranexamic acid. Role 1 care is vital to patient survival, including care from point of injury to battalion aid stations, but the guidelines available to instruct this care and the guidance on which personnel should provide this care are conflicting. This lack of clarity and consistency may adversely impact treatment outcomes. The reduction or elimination of conflicting information across the various guidelines, augmentation of guidance for pediatric care, more specific guidance for unique levels of care, and clearer delineation of the Role 1 phases of care (as well as which guidelines are most appropriate to each) should be considered as urgent priorities within the military medical community.


Regional homogeneity alterations in multi-frequency bands in tension-type headache: a resting-state fMRI study.
In this study, we aimed to investigate the spontaneous neural activity in the conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz, and slow-5: 0.01-0.027 Hz) in tension-type headache (TTH) patients with regional homogeneity (ReHo) analyses. Thirty-eight TTH patients and thirty-eight healthy controls (HCs) underwent resting-state functional magnetic resonance imaging (RS-fMRI) scanning to investigate abnormal spontaneous neural activity using ReHo analysis in conventional frequency band (0.01-0.08 Hz) and two sub-frequency bands (slow-4: 0.027-0.073 Hz and slow-5: 0.01-0.027 Hz). In comparison with the HC group, patients with TTH exhibited ReHo increases in the right medial superior frontal gyrus in the conventional frequency band (0.01-0.08 Hz). The between group differences in the slow-5 band (0.01-0.027 Hz) highly resembled the differences in the conventional frequency band (0.01-0.08 Hz); even the voxels with increased ReHo were spatially more extensive, including the right medial superior frontal gyrus and the middle frontal gyrus. In contrast, no region showed significant between-group differences in the slow-4 band (0.027-0.073 Hz). The correlation analyses showed no correlation between the ReHo values in TTH patients and VAS scores, course of disease and number of seizures per month in conventional band (0.01-0.08 Hz), slow-4 band (0.027-0.073 Hz), as well as in slow-5 band (0.01-0.027 Hz). The results showed that the superior frontal gyrus and middle frontal gyrus were involved in the integration and processing of pain signals. In addition, the abnormal spontaneous neural activity in TTH patients was frequency-specific. Namely, slow-5 band (0.01-0.027 Hz) might contain additional useful information in comparison to slow-4 band (0.027-0.073 Hz). This preliminary exploration might provide an objective imaging basis for the understanding of the pathophysiological mechanism of TTH.


The use of iodinated free fatty acids for assessing fatty acid metabolism.
Free fatty acid is a major substrate fuel for normal myocardium. Cardiovascular disease is frequently associated with impairment of fatty acid oxidation. Therefore assessment of fatty acid metabolism may be an important tool for the early detection of myocardial abnormalities and may provide insight into pathologic heart conditions. Although carbon 11-labeled palmitate is a well-established tracer for probing myocardial fatty acid metabolism, a variety of iodinated fatty acid compounds have been introduced for assessing fatty acid metabolism, including straight-chain and branched-chain fatty acid compounds. Straight-chain fatty acid has advantages for measuring fatty acid oxidation on the basis of tracer clearance from the myocardium. Branched-chain fatty acid can be trapped in the myocardium without further washout and uptake in the myocardium may reflect fatty acid retention and some aspect of fatty acid metabolism. A long tracer retention period makes feasible the acquisition of single-photon emission computed tomographic images. This review examines the characteristics of both types of tracers and our recent clinical experience with beta-methyliodophenyl pentadecanoic acid, which has potential for detecting and characterizing both ischemic heart disease and cardiomyopathy.


Perfusion reversed-phase high-performance liquid chromatography for protein separation from detergent-containing solutions: an alternative to gel-based approaches.
Detergents are frequently used for the solubilization of membrane proteins during and after purification steps. Unfortunately some of these detergents impair chromatographic separations and mass spectrometry (MS) analysis. Perfusion reversed-phase high-performance liquid chromatography (RP-HPLC) using POROS materials is suited for separating intact proteins solubilized by detergents due to the particles' highly diffusive pores and chemical stability. In this article, the use of perfusive reversed-phase material packed into small inner diameter capillary columns is presented as a cheap, rapid, and efficient method for the removal of different types of detergents from protein solutions. The ability to purify and separate the subunits of membrane protein complexes with self-packed capillary columns is exemplified for bovine cytochrome bc(1) complex. Even highly hydrophobic subunits can be detected in collected fractions by intact mass measurements and identified after proteolytic digestion and matrix-assisted laser desorption/ionization tandem MS (MALDI MS/MS). The comparison with a gel-based approach shows that this method is a valuable alternative for purification and separation of intact proteins with subsequent MS analysis and that hydrophobic proteins are even better represented in the LC-based approach.


Osteosarcoma.
Osteosarcoma is the most common bone tumor of children and adolescents. The peak incidence of the disease is in the 15 to 19 year age group. The disease is more commonly seen in males than females. While several factors, including exposure to radiation, genetic disorders such as retinoblastoma, and high rate of bone growth, have been associated with osteosarcoma, in most cases no definite etiology can be established. Osteosarcoma usually originates in the metaphyseal region of long bones and extends through the cortex, causing varying degrees of bone destruction and expansion of periosteum. The radiographic appearance caused by this process is often referred to as "sun burst" sign. Positive diagnosis of osteosarcoma is made by histopathology. The histopathological classification of osteosarcoma can also predict the degree of aggressive behavior of this tumor and thus has prognostic significance. Surgery, including amputation or limb-salvage procedure, is the mainstay of treatment of osteosarcoma. It is now unequivocally established that adjuvant chemotherapy will prolong the survival of patients with this disease. Chemotherapy agents often used include platinum derivates, methotrexate, vincristine, cyclophosphamide, adriamycin, actinomycin D, bleomycin and DTIC. Depending on surgical decision, these agents can be used prior to or after the operation. Immediate fitting with prosthesis and provision of appropriate medical and psychological support in the care of these patients is essential.


Lysine-specific demethylase 1 deficiency modifies aldosterone synthesis in a sex-specific manner.
Biologic sex influences the development of cardiovascular disease and modifies aldosterone (ALDO) and blood pressure (BP) phenotypes: females secrete more ALDO, and their adrenal glomerulosa cell is more sensitive to stimulation. Lysine-specific demethylase 1 (LSD1) variants in Africans and LSD1 deficiency in mice are associated with BP and/or ALDO phenotypes. This study, in 18- and 40-week-old wild type (WT) and LSD1+/- mice, was designed to determine whether (1) sex modifies ALDO biosynthetic enzymes; (2) LSD1 deficiency disrupts the effect of sex on these enzymes; (3) within each genotype, there is a positive relationship between ALDO biosynthesis (proximate phenotype), plasma ALDO (intermediate phenotype) and BP levels (distant phenotype); and (4) sex and LSD1 genotype interact on these phenotypes. In WT mice, female sex increases the expression of early enzymes in ALDO biosynthesis but not ALDO levels or systolic blood pressure (SBP). However, enzyme expressions are shifted downward in LSD1+/- females vs males, so that early enzyme levels are similar but the late enzymes are substantially lower. In both age groups, LSD1 deficiency modifies the adrenal enzyme expressions, circulating ALDO levels, and SBP in a sex-specific manner. Finally, significant sex/LSD1 genotype interactions modulate the three phenotypes in mice. In conclusion, biologic sex in mice interacts with LSD1 deficiency to modify several phenotypes: (1) proximal (ALDO biosynthetic enzymes); (2) intermediate (circulating ALDO); and (3) distant (SBP). These results provide entry to better understand the roles of biological sex and LSD1 in (1) hypertension heterogeneity and (2) providing more personalized treatment.


Early gallbladder cancer.
The majority of patients with gallbladder cancer (GBC) have advanced disease at the time of diagnosis and are unresectable. Longterm survival is usually seen in a subset of patients with early GBC (EGBC)-cancer confined to the mucosa (pT1a) and muscularis (pT1b). Management guidelines of EGBC are not yet defined and are controversial. The purpose of this article is to evaluate the diagnostic aspects and effects of resectional procedures on survival outcome in patients with EGBC. EGBC was defined as cancer confined to the mucosa (pT1a) or muscularis (pT1b) according to the TNM classification. Clinicopathological details and survival data of 14 patients who had EGBC were analyzed. There were 9 women and 5 men, with a mean age of 60 years. A definite preoperative diagnosis was possible in only three patients and three patients were diagnosed at operation; the majority of patients were diagnosed incidentally after cholecystectomy for associated gallstones. Two patients underwent extended cholecystectomy and 12 patients underwent simple cholecystectomy. Two patients had pT1a and 12 had pT1b lesions. Mean (SD) survival was 71.5 (12.2) months and median survival was 42 months. There were five treatment failures with locoregional recurrence and death; all with pT1b tumors were treated by simple cholecystectomy. Cumulative 1-, 3-, and 5-year survival was 92%, 68%, and 68% respectively [corrected]. Simple cholecystectomy is an adequate treatment only for mucosal GBC. Patients with pT1b tumors require extended cholecystectomy. Incidental GBC extending up to the muscularis merits early reoperation for completion of extended cholecystectomy, which offers the only chance of cure.


The bulbo-spinal indoleaminergic pathway in the frog.
The role of the bulbo-spinal indoleaminergic pathway of the frog was investigated. Using the isolated spinal cord preparation, responses of motoneurons of segments 9 and 10 to lateral column stimulation were recorded from ventral roots (LC-VRP) and by intracellularly placed microelectrodes. Control responses were compared to those obtained after addition of substances known to alter indoleaminergic synthesis or receptor activation. Responses from spinal cords of animals that were pretreated with indoleamine-depleting agents were compared to mean control responses. Procedures that inhibited indoleamine synthesis or blocked indoleamine receptors reduced motoneuronal activity. This was manifested as an increase in mean latency and a decrease in amplitude of the monosynaptic LC-VRP, an increased duration of suppression following an LC conditioning stimulus, and a decrease in spontaneous activity. In contrast to intracellularly recorded responses from control cords, those recorded under these conditions typically showed single spikes with longer latencies. Additions of indoleamine precursors to normal cords or to cords depleted of monoamines by reserpine shortened mean latencies, increased amplitudes of LC-elicited responses and caused an increase in spontaneous activity. These observations were recorded both extracellularly and intracellularly. Our results suggest that the bulbo-spinal indoleaminergic pathway modulates the output of motoneurons of the frog spinal cord.


Three simultaneous primary urologic malignancies iA single patient: A case report and review of the literature.
The simultaneous appearance of several primary cancers is rare. We report the case of a 77-year-old man admitted to the Mohammed V military hospital in Rabat (university hospital) and presenting severe dysuria on the PSA test which was 10.83 ng / ml. The prostate MRI performed revealed a suspected lesion. He had left renal colic associated with hematuria two weeks later. A CT scan of the abdomen and pelvis performed revealed a 14 × 12 mm middle and lower calyx excretory tract tumor on the left and a 27.6 × 26.4 lower right polar kidney tumor enhanced after injection of product from contrast. The prostate biopsy confirmed an adenocarcinoma of the prostate. He first underwent a left nephroureterectomy for the tumor of the excretory tract, followed by radiotherapy combined with hormone therapy for his adenocarcinoma. It was decided to monitor the tumor of the right kidney. The literature contains only a few case reports and reviews of patients with three or more synchronous malignancies. We report the case of a man in whom three different cancers were found over a period of three months. The patient had no significant medical history, such as a family history of cancer or chemotherapy other than old age and chronic smoking. Therefore, we suggest that these factors may favor the occurrence of several synchronous primary cancers. There is no consensus on the treatment of multiple malignant tumors. Patient care is individual, by a multidisciplinary team, accounting for the type and the stage of each tumor with a more conservative approach.


Taxonomic review of Drilus Olivier, 1790 (Elateridae: Agrypninae: Drilini) from Asia Minor, with descriptions of seven new species and comments on the female antennal morphology in Drilini.
The neotenic elaterid genus Drilus Olivier, 1790 in Asia Minor is reviewed. Twelve species are recognized, of which seven are described as new: Drilus badius sp. nov., D. huijbregtsi sp. nov., D. mertliki sp. nov., D. robustus sp. nov., D. sanliurfensis sp. nov., D. teunisseni sp. nov., and D. turcicus sp. nov. All known species are listed with diagnoses, data on variability and distribution. A key to the males of Drilus species in Asia Minor is provided and information on prey of known larvae is summarized. Antennal morphology of Drilini females is briefly discussed.


Impulse blockade by intraocular tetrodotoxin during optic regeneration in goldfish: HRP-EM evidence that the formation of normal numbers of optic synapses and the elimination of exuberant optic fibers is activity independent.
Optic fibers and synapses labeled with HRP were counted in the primary optic innervation layer of tectum after continuously blocking visual impulse activity with TTX during regeneration. Normal numbers of optic and nonoptic fibers and synapses were found at both 30 and 60 d, and key ultrastructural features of optic afferents such as fiber fasciculation, myelination, terminal clustering, synaptogenesis onto different classes of postsynaptic targets and general morphology were not notably affected by impulse blockade. These findings indicate that during regeneration the normal proliferation and elimination of optic fibers and the formation of normal numbers of optic synapses are not regulated by activity and are consistent with a pattern formation role for impulse activity rather than a trophic one.


Assessing the oppositional culture explanation for Mexican students.
Using nationally representative data from the High School Longitudinal Study (HSLS), I assess the oppositional culture explanation for Mexican students. First, I examine if there are differences between Mexican and White students in their academic behaviors, attitudes, and friends' academic orientation. Second, I examine if these measures account for the racial disparity in academic outcomes between Mexican and White students. The results show that there are few differences between Mexican and White students in measures of school-related behaviors, attitudes, and friends' academic orientation. The second part of the analysis suggests that, in general, these measures for behaviors, attitudes, and friends' academic orientation do not explain much of the differences in academic achievement between Mexican and White students. The findings from the study indicate that the oppositional culture explanation does not account for this disparity in achievement.


An alternative treatment method for fluorosurfactant-containing wastewater by aerosol-mediated separation.
The treatment of fluorosurfactant-containing wastewater is still challenging nowadays. Here, a method is presented to remove fluorosurfactants from water, amongst others from electroplating wastewater. This elimination technique is based on the generation of gas bubbles in solution, enrichment and scavenging of fluorosurfactants by transport of the gas bubbles to the water surface. Finally the bubbles collapse and release an aerosol which is enriched with fluorosurfactants. By sampling of the released aerosols a mass balance was established for 6:2 fluorotelomer sulfonic acid (6:2 FTSA). Thereby 99.8% of the initial amount was revocered in the collected aerosols. Fluorosurfactant concentration in solution decreased exponentially with half-lives ranging from 2 to 6 min for 6:2 FTSA as well as perfluorooctane carboxylate (PFOA) and perfluorooctane sulfonate (PFOS). Elimination rate in defined matrix (0.2 M H2SO4) within 60 min was 99.6, 99.9 and 99.8% for 6:2 FTSA, PFOA and PFOS, respectively. The removal rate of 6:2 FTSA increased in solutions with higher ionic strength. Different wastewater from an electroplating industry containing 6:2 FTSA was treated with the described method without any sample pre-treatment and elimination of 6:2 FTSA took place with the same effectiveness as in synthetic matrices.


Transcriptional regulation of photoprotection in dark-to-light transition-More than just a matter of excess light energy.
In nature, photosynthetic organisms are exposed to different light spectra and intensities depending on the time of day and atmospheric and environmental conditions. When photosynthetic cells absorb excess light, they induce nonphotochemical quenching to avoid photodamage and trigger expression of "photoprotective" genes. In this work, we used the green alga Chlamydomonas reinhardtii to assess the impact of light intensity, light quality, photosynthetic electron transport, and carbon dioxide on induction of the photoprotective genes (LHCSR1, LHCSR3, and PSBS) during dark-to-light transitions. Induction (mRNA accumulation) occurred at very low light intensity and was independently modulated by blue and ultraviolet B radiation through specific photoreceptors; only LHCSR3 was strongly controlled by carbon dioxide levels through a putative enhancer function of CIA5, a transcription factor that controls genes of the carbon concentrating mechanism. We propose a model that integrates inputs of independent signaling pathways and how they may help the cells anticipate diel conditions and survive in a dynamic light environment.


High-permeability functionalized silicone magnetic microspheres with low autofluorescence for biomedical applications.
Functionalized magnetic microspheres are widely used for cell separations, isolation of proteins and other biomolecules, in vitro diagnostics, tissue engineering, and microscale force spectroscopy. We present here the synthesis and characterization of a silicone magnetic microsphere which can be produced in diameters ranging from 0.5 to 50 μm via emulsion polymerization of a silicone ferrofluid precursor. This bottom-up approach to synthesis ensures a uniform magnetic concentration across all sizes, leading to significant advances in magnetic force generation. We demonstrate that in a size range of 5-20 μm, these spheres supply a full order of magnitude greater magnetic force than leading commercial products. In addition, the unique silicone matrix exhibits autofluorescence two orders of magnitude lower than polystyrene microspheres. Finally, we demonstrate the ability to chemically functionalize our silicone microspheres using a standard EDC reaction, and show that our folate-functionalized silicone microspheres specifically bind to targeted HeLa and Jurkat cells. These spheres show tremendous potential for replacing magnetic polystyrene spheres in applications which require either large magnetic forces or minimal autofluorescence, since they represent order-of-magnitude improvements in each. In addition, the unique silicone matrix and proven biocompatibility suggest that they may be useful for encapsulation and targeted delivery of lipophilic pharmaceuticals.


Ambient ozone exposure and depression among middle-aged and older adults: Nationwide longitudinal evidence in China.
Epidemiological studies have linked long-term ozone (O3) exposure with depression in developed countries. However, available literature is sparse and exists great heterogeneities. We aimed to investigate the association of long-term O3 exposure with depression among Chinese middle-aged and older adults. We designed a repeated measurement study based on longitudinal data from four waves (2011, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). Annual mean O3 concentrations assessed through machine learning-based spatiotemporal models were assigned to each participant at city level. Depression score was measured using the 10-item Center for Epidemiologic Studies Depression scale (CES-D-10), with scores above the cut-off point of ten defined as depressive symptom. Mixed-effects models were used to evaluate the impact of O3 on depression score and depressive symptom, and quantify the concentration-response (C-R) relationships. Subgroup analyses were performed to examine the potential effect modifications. A total of 19,582 participants with 60,125 visits were included in our analysis, with mean depression score of 8.1 (standard deviation: 6.3). Multivariable-adjusted mixed-effects model estimated a 6.34% (95% confidence interval [CI]: 3.34%, 9.43%) increase in depression score and an odds ratio (OR) of 1.29 (95% CI: 1.16, 1.45) for depressive symptom associated with per 10-μg/m3 rise in annual mean O3 exposure. Significantly elevated risks were identified only at high concentrations (approximately ≥90 μg/m3). Participants who suffered from chronic diseases had a significant increased risk of depression (% Change in depression score: 8.42% [95% CI: 4.79%, 12.17%], and OR: 1.42 [95% CI: 1.24, 1.62]), and an evident effect modification was identified for depressive symptom (P = 0.01). Our study provided novel evidence that long-term O3 exposure could be a risk factor for depression among Chinese middle-aged and older adults. Our findings may have significant implications for formulating policies in reducing disease burden of depression by controlling air pollution.


[Health ethology of the fox and antirabies vaccine in the Italian experience].
In order to contribute to the planning of antirabies oral vaccination of foxes a series of ethological and ecological investigations have been carried out. The results obtained are briefly summarized and discussed together with experimental data on antirabies immunization of dogs and foxes with different vaccines.


Kinetic and solvent deuterium isotope effects in the oxidation of putrescine catalysed by enzyme diamine oxidase.
In this study, the kinetic isotope effects and solvent isotope effects in the reaction of the deamination of [(1R)-(2)H ] putrescine--catalysed by enzyme diamine oxidase (EC 126.96.36.199)--were determined using a non-competitive spectroscopic method. Putrescine, stereospecifically labelled with deuterium, was obtained by enzymatic decarboxylation of l-ornithine that was carried out in a fully deuteriated incubation medium.


Cortical activity in vertebrate eggs. I: The activation waves.
We present a physical model for the propagation of chemical and mechanical waves on the surface of vertebrate eggs. As a first step we analyzed the propagation of the calcium wave observed to sweep over the surface of the Medaka egg (Gilkey et al., 1978). It has been assumed that this wave is driven by a mechanism of calcium-stimulated-calcium-release. By formulating this hypothesis mathematically we can use the observed wavefront data to obtain a map of cortical reactivity. This map indicates a gradient of reactivity along the egg: highest in the animal hemisphere and tapering off towards the vegetal hemisphere. The cortex of Xenopus eggs is also capable of propagating a calcium wave (Busa & Nuccitelli, 1985). At about the same time a wave of expansion followed by a wave of contraction sweeps across the egg surface (Takeichi et al., 1984). We have proposed a mechanism for this wave pair based on the physical chemistry of actomyosin gels. The calcium wave activates solation factors which sever some of the actin chains which leads to an osmotic swelling of the gel. Calcium also activates the contractile machinery of the actomyosin system which causes the gel to contract. The contraction lags the swelling because of the nature of the kinetics: solation and swelling is a more rapid process than contraction. By writing the equations for gel expansion and contraction we can mimic the mechanical and chemical wave propagation by a computer simulation. If the model is correct this provides a method for using the waves as a diagnostic of the mechanochemical properties of the egg cortex.


Arboviral causes of non-specific fever and myalgia in a fever hospital patient population in Cairo, Egypt.
Fever and myalgia are non-specific clinical manifestations of illness which commonly occur in patients with arboviral disease. In Egypt, such illness is often mis-diagnosed as "influenza". To determine arboviral aetiology in patients admitted with fever and myalgia, acute and convalescent sera samples were obtained from 55 patients admitted with these clinical manifestations to the Imbaba Fever Hospital, Giza, Egypt, during October and November 1984. Based on viral isolation, and a comparison of acute and convalescent sera, 4 patients (7%) had acute arboviral infections. Haemagglutination inhibition and indirect immunofluorescence tests showed that one had West Nile virus (WNV) infection, 2 had sandfly fever virus-Naples (SFN), and 1 had sandfly fever virus-Sicilian (SFS) infection. SFN was isolated from the acute serum sample of 1 of the 2 patients with SFN infection.


Towards Elucidating the Rotary Mechanism of the Archaellum Machinery.
Motile archaea swim by means of a molecular machine called the archaellum. This structure consists of a filament attached to a membrane-embedded motor. The archaellum is found exclusively in members of the archaeal domain, but the core of its motor shares homology with the motor of type IV pili (T4P). Here, we provide an overview of the different components of the archaellum machinery and hypothetical models to explain how rotary motion of the filament is powered by the archaellum motor.


A pre-concentration procedure using coprecipitation for determination of lead and iron in several samples using flame atomic absorption spectrometry.
The present paper proposes a pre-concentration procedure for determination of lead and iron in several samples by flame atomic absorption spectrometry. In it, lead(II) and iron(III) ions are coprecipitated using the violuric acid-copper(II) system as collector. Afterwards, the precipitate is dissolved with 1M HNO3 solution and the metal ions are determined. The optimization step was performed using factorial design involving the variables: pH, violuric acid mass (VA) and copper concentration (Cu). Using the optimized experimental conditions, the proposed procedure allows the determination these metals with detection limits of 0.18 microg L(-1) for iron and 0.16 microg L(-1) for lead. The effects of foreign ions on the pre-concentration procedure were also evaluated and the results demonstrated that this method could be applied for determination of iron and lead in several real samples. The proposed method was successfully applied to the analysis of seawater, urine, mineral water, soil and physiological solution samples. The concentrations of lead and iron achieved in these samples agree well with others data reported in the literature.


Review of recurrent polyps and cancer in 500 patients with initial colonoscopy for polyps.
Five hundred patients with 1240 polyps removed by colonoscopy and polypectomy over a 13-year period are the subject of ongoing follow-up study. Ninety-three percent of the patients have been followed an average of 53 months with a recurrence rate of polypoid disease in 26 percent, of which approximately 7 percent demonstrated malignant changes. This compares to a rate of 7 percent metachronous cancer in patients with a malignancy demonstrated at any time in the past. The highest risk group for recurrence are patients with more than four polyps at initial colonoscopy, with a 59 percent recurrence rate. The following recommendations for follow-up are made: 1) Flexible sigmoidoscopy is adequate yearly follow-up if the original polyps are confined to the rectum and sigmoid. 2) Colonoscopy should be carried out the first year if the original polyps are beyond the rectum and sigmoid, and yearly until the colon is cleared of recurring lesions. 3) Colonoscopy is indicated in patients with cancer before surgery if possible; if not, within six months after resection. 4) Interval six-month examinations are indicated in patients with colon cancer and multiple synchronous polyps until the colon is cleared. 5) Large, sessile polyps resected piecemeal require a three-month follow-up until gone. 6) When the above conditions are met, colonoscopy at three-year intervals is adequate for long-term follow-up of neoplastic polyps to detect and prevent early malignancy.


Visceral leishmaniasis complicated by hemophagocytic lymphohistiocytosis: A case report from a nonendemic area.
Visceral leishmaniasis and hemophagocytic lymphohistiocytosis share many features in common and may coincide in the same patient. Timely diagnosis and management of visceral leishmaniasis could save patients from unnecessary toxic treatment. Visceral leishmaniasis and hemophagocytic lymphohistiocytosis share many clinical features in common and may coexist in the same patient. Visceral leishmaniasis should be promptly ruled out in patients coming from endemic areas before starting immunosuppressive therapy for hemophagocytic lymphohistiocytosis. The mainstay treatment, in this case, is anti-leishmania medications preferably liposomal amphotericin-B.


Compartment and cell-type specific hypoxia responses in the developing Drosophila brain.
Environmental factors such as the availability of oxygen are instructive cues that regulate stem cell maintenance and differentiation. We used a genetically encoded biosensor to monitor the hypoxic state of neural cells in the larval brain of Drosophila The biosensor reveals brain compartment and cell-type specific levels of hypoxia. The values correlate with differential tracheolation that is observed throughout development between the central brain and the optic lobe. Neural stem cells in both compartments show the strongest hypoxia response while intermediate progenitors, neurons and glial cells reveal weaker responses. We demonstrate that the distance between a cell and the next closest tracheole is a good predictor of the hypoxic state of that cell. Our study indicates that oxygen availability appears to be the major factor controlling the hypoxia response in the developing Drosophila brain and that cell intrinsic and cell-type specific factors contribute to modulate the response in an unexpected manner.This article has an associated First Person interview with the first author of the paper.


Targeted neural network interventions for auditory hallucinations: Can TMS inform DBS?
The debilitating and refractory nature of auditory hallucinations (AH) in schizophrenia and other psychiatric disorders has stimulated investigations into neuromodulatory interventions that target the aberrant neural networks associated with them. Internal or invasive forms of brain stimulation such as deep brain stimulation (DBS) are currently being explored for treatment-refractory schizophrenia. The process of developing and implementing DBS is limited by symptom clustering within psychiatric constructs as well as a scarcity of causal tools with which to predict response, refine targeting or guide clinical decisions. Transcranial magnetic stimulation (TMS), an external or non-invasive form of brain stimulation, has shown some promise as a therapeutic intervention for AH but remains relatively underutilized as an investigational probe of clinically relevant neural networks. In this editorial, we propose that TMS has the potential to inform DBS by adding individualized causal evidence to an evaluation processes otherwise devoid of it in patients. Although there are significant limitations and safety concerns regarding DBS, the combination of TMS with computational modeling of neuroimaging and neurophysiological data could provide critical insights into more robust and adaptable network modulation.


Exploring the perspectives of medical students on application of e-learning in medical education during the COVID-19 pandemic.
The use of e-learning has become mandatory during the COVID-19 pandemic. However, there are many barriers to applying e-learning in medical education. This study aimed to explore medical students' perspectives on the application of e-learning in medical education during the COVID-19 pandemic. This Q-methodology explorative study was conducted in Kurdistan Region of Iraq. A sample of 37 medical students was purposively selected to represent different characteristics. The students distributed 37 statements representing different aspects of e-learning in medical education into a nine-point scoring grid from "least agree" to "most agree." Data analysis revealed three distinct viewpoints. The first viewpoint, complete dependence on e-learning, emphasized a preference for e-learning to continue medical education and complete the study year with a minimal return to study halls or practical/clinical sessions. The second viewpoint, opponents of applying e-learning in medical education, included a generally negative view about e-learning and its role in medical education during the COVID-19 pandemic. The third viewpoint, e-learning as a supplement to medical education, emphasized a generally positive view about e-learning and considered it a supplement to the theoretical parts of medical education during the pandemic. The three diverse viewpoints are primarily distinguished by the availability of e-learning experience and skills, availability of technology, risk perception of COVID-19, and the need for in-hospital clinical teaching. Provision of necessary facilities and training is required to strengthen the role of e-learning in medical education. A safe environment is needed for on-campus or hospital clinical teaching.


Surgical implications of the superior oblique frenulum.
The superior oblique frenulum is a fascial membrane that prevents substantial separation of the superior rectus muscle and SO tendon. In three patients, the superior rectus muscle was disinserted and temporarily suspended 6, 8, 10, 12, and 14 mm in random order from its insertion. The change in position of the anterior edge of the superior oblique tendon from the superior rectus muscle insertion was measured before and after severing the frenulum structure. In four other patients undergoing superior oblique recession, the superior oblique tendon was disinserted at its insertion temporally. The amount of recession that spontaneously occurred was measured before and after severing the frenulum. In the first group, there was essentially a one-to-one correlation between the posterior movement of the superior oblique tendon and the amount of superior rectus recession for recessions up to 10 mm. After severing the frenulum, the anterior portion of the superior oblique tendon was positioned less posteriorly. It measured less than 1.2 mm for superior rectus recessions up to 14 mm. For the second group, the mean suspension distance of the cut end of the disinserted superior oblique tendon was 2.4 +/- 0.4 mm before stripping the frenulum as compared with 8.5 +/- 0.7 mm after stripping the frenulum (Student's t-test, p = 0.0011). The frenulum pulls the superior oblique tendon posteriorly as the superior rectus muscle is recessed and constrains the superior oblique tendon after disinsertion. How this connection is handled at the time of surgery may have implications for superior rectus recessions and superior oblique tendon surgery.


Is a family equal to the sum of its parts? Estimating family-level well-being for cost-effectiveness analysis.
Cost-effectiveness (CEA) analysis of health interventions focuses primarily on individual-level costs and benefits. However, health interventions intended for individuals often have implications for other members of an individual's family and the overall functioning of the family. While researchers have assessed the effects of health interventions on multiple family members, CEA has not routinely incorporated measures of effectiveness or costs from multiple family members. We could imagine, however, that CEA might over- or under-estimate the effects of health interventions if they are limited to individuals targeted by the intervention. Family-level CEA would consider the well-being of and costs borne by multiple family members in response to an individual-level intervention, and potentially lead to more appropriate resource allocation. Using the health plan as a working frame of reference, we explore conceptual issues related to estimating effectiveness at the level of the family for use in CEA.


Year-round daylight saving and serious or fatal road traffic injuries in children in the north-east of England.
It has been suggested that year-round daylight saving would reduce road traffic injuries. and results Using 15 years of police data from north-east England, we estimate that 6.9 (95 per cent CI 1.5-12.6) fewer serious or fatal road traffic injuries to child pedestrians would have occurred in this area over this period had year-round daylight saving operated (equivalent to 0.5 per year). The results suggest that operating daylight saving year-round would have a small but tangible effect on the number of serious and fatal road traffic injuries in children in this area. Further work is required to assess the community wide impact of year round daylight saving.


TNF-alpha gene promoter polymorphism at nucleotide -308 and the inflammatory response and oxidative stress induced by cardiac surgery: role of heart failure and medical treatment.
Increased TNF-alpha during cardiac surgery is thought to be responsible for perioperative complications. The TNF-alpha gene promoter polymorphism G/A at position -308 has been associated with enhanced TNF-alpha secretion, as has been heart failure. Therefore, the aims of this study were to investigate: (i) whether the TNF-alpha G/A polymorphism is associated with exacerbation of TNF-alpha plasma levels during cardiac surgery; (ii) whether TNF-alpha production is further increased by heart failure and influenced by medical treatment; and (iii) whether this polymorphism is associated with increased oxidative stress and perioperative complications. The TNF-alpha gene promoter polymorphism was studied in 100 consecutive patients undergoing cardiac surgery. Of them, 65 were identified with the common allele G/G, whereas 34 patients were with the G/A polymorphism and 1 was A/A. TNF-alpha plasma levels (ELISA) and peroxynitrite content in peripheral blood lymphocytes (flow cytometry) were measured before surgery, before cardiopulmonary bypass (CPB), and 30 min, 4 and 24h after initiation of CPB. The changes observed in TNF-alpha plasma levels during cardiac surgery were unaffected by the G/A polymorphism. TNF-alpha values were elevated before surgery in patients with more advanced NYHA class (1.66+/-0.14, 2.29+/-0.06 and 2.57+/-0.11 ln(mmol/l+1), for NYHA I, II and III; p=0.004) but again they were not correlated with the G/A polymorphism. Peroxynitrite content in lymphocytes was similar upon the initiation of surgery in the G/A and G/G groups and also in all NYHA class groups, and thereafter levels were similarly increased by surgery in all groups. However, analysis of the effect of preoperative medication showed that the mitoK(ATP) channel opener nicorandil reduced TNF-alpha values before surgery and blunted the increase in peroxynitrite caused by surgery. Perioperative complications were not related to either TNF-alpha polymorphism or TNF-alpha and peroxynitrite levels. The TNF-alpha gene promoter polymorphism G/A at position -308 does not influence TNF-alpha plasma levels during cardiac surgery, is not associated with greater oxidative stress, and does not result in a greater incidence of perioperative complications. However, importantly, treatment with the mitoK(ATP) channel opener nicorandil prior to surgery significantly reduced basal TNF-alpha values and also the oxidative stress induced by surgery.


Validation of an ex vivo human cervical tissue model for optical imaging studies.
To establish and validate an ex vivo human cervical tissue model for optical coherence tomography (OCT) studies with special emphasis on investigating time dependent structural changes of the epithelium. Four hundred OCT images were taken from 80 unsuspicious and suspicious areas of 18 fresh conisation specimens immediately after resection (0 hour) and 1, 2, 3, and 4 hours, referred to as waiting times in the following, postoperatively and compared to the corresponding histology. For each 2D-OCT-image, a 1D-intensity profile was generated. The profiles were analyzed with respect to systematic differences which may result from different waiting times, employing discriminant analysis (DA). The different waiting times do not appear to imply significant differences among the corresponding OCT-images as represented by the intensity profiles. We conclude that the proposed cervical tissue model appears to be applicable for ex vivo OCT studies.


How hospital-based health care providers perceive clinical librarian services: a qualitative review protocol.
The objective of the review is to evaluate how health care providers working in hospitals perceive clinical librarian services. Clinical librarianship programs existed as early as 1971; however, there is a lack of evidence on their effectiveness in impacting health care outcomes. Studies report primarily on programs supporting medicine, although these programs also support other health care providers. In order to affect outcomes, particularly those focused on patient-centered, evidence-based care, clinical librarians need insight into how hospital health care providers perceive clinical librarian services. The review will consider studies that include any health care provider who works within a hospital, including surgical, clinical, and inpatient units. Studies that focus on qualitative data about clinical librarian services, published from 1971 onward, will be eligible for inclusion. The primary databases to be searched are PubMed, CINAHL, Embase, PsycINFO, Library Literature & Information Science, LISTA (Library, Information Science & Technology Abstracts), and Web of Science. Studies will be selected based on their assessment against the inclusion criteria by two independent reviewers. Eligible studies will be critically appraised for methodological quality. Data will be extracted using a standardized tool, and findings pooled and synthesized using a meta-aggregation approach.


Minimally Invasive Neurosurgery for Epilepsy Using Stereotactic MRI Guidance.
Medically refractory epilepsy is associated with significant morbidity and mortality. Surgery is a safe and effective option for some patients, however the opportunity exists to develop less invasive and more effective surgical options. To this end, multiple minimally invasive, image-guided techniques have been applied to the treatment of epilepsy. These techniques can be divided into thermoablative and disconnective techniques. Each has been described in the treatment of epilepsy only in small case series. Larger series and longer follow up periods will determine each option's place in the surgical armamentarium for the treatment of refractory epilepsy but early results are promising.


Increased sugar concentration in response to a wide range of pollinator sounds can be adaptive for the plant: answer to Raguso et al.
In Veits et al., we showed that flowers respond to a range of pollinator sounds by increased nectar sugar concentration. Here we clarify that (1) our argument is relevant to most pollinators, and not limited to bees (2) specifically, bees do access Oenothera Drumondii nectar in this area.


Effects of low and high frequency repetitive transcranial magnetic stimulation of the primary motor cortex on contingent negative variations in normal subjects.
The state of primary motor cortex (M1) excitability is crucial for the processing of voluntary movement. We aimed to test the modulation induced by 1 Hz and 5 Hz repetitive transcranial magnetic stimulation (rTMS) of M1 on both early and late components of the contingent negative variation (CNV) and on the motor reaction in normal subjects. The CNV was evaluated in basal, and after 15 min of real or sham 1 Hz and 5 Hz stimulation of the left motor cortex in 7 right handed volunteers. Inhibition of motor cortex, due to rTMS stimulation, resulted in an amplitude increase of early and late components of CNV, and a slight reducing effect on motor reaction times, while 5 Hz stimulation did not change CNV amplitude. In normal subjects transient inhibition of motor cortex causes an increase of cortical events preceding external-cued voluntary movements, as a probable compensatory phenomena able to maintain an efficient motor performance.


[A fun information tool for patients after a stroke].
"L'ABC de l'AVC®" [A complete guide to stroke] is a fun information tool created for stroke patients by the multidisciplinary team of a neurovascular unit. It is designed to improve patient knowledge of the disease, its causes and consequences, preparing them to better understand what the future holds. It also serves as a training tool for professionals.


Lead exposure activates the Nrf2/Keap1 pathway, aggravates oxidative stress, and induces reproductive damage in female mice.
Lead, a common metallic contaminant, is widespread in the living environment, and has deleterious effects on the reproductive systems of humans and animals. Although numerous toxic effects of lead have been reported, the effects and underlying mechanisms of the impacts of lead exposure on the female reproductive system, especially oocyte maturation and fertility, remain unknown. In this study, mice were treated by gavage for seven days to evaluate the reproductive damage and role of Nrf2-mediated defense responses during lead exposure. Lead exposure significantly reduced the maturation and fertilization of oocytes in vivo. Additionally, lead exposure triggered oxidative stress with a decreased glutathione level, increased amount of reactive oxygen species, and abnormal mitochondrial distribution. Moreover, lead exposure caused histopathological and ultrastructural changes in oocytes and ovaries, along with decreases in the activities of catalase, glutathione peroxidase, total superoxide dismutase, and glutathione-S transferase, and increases in the levels of malonaldehyde in mouse ovaries. Further experiments demonstrated that lead exposure activated the Nrf2 signaling pathway to protect oocytes against oxidative stress by enhancing the transcription levels of antioxidant enzymes. In conclusion, our study demonstrates that lead activates the Nrf2/Keap1 pathway and impairs oocyte maturation and fertilization by inducing oxidative stress, leading to a decrease in the fertility of female mice.


Palladium-catalyzed cyclization of bromoenynamides to tricyclic azacycles: synthesis of trikentrin-like frameworks.
Palladium-catalyzed cascade cyclization of bromoenynamides equipped with an additional alkyne or ynamide substituent affords azatricyclic products. Using 5- to 7-membered ring tethers, this chemistry offers a regiospecific route to highly-functionalized azacycles. Elaboration to the trikentrin B skeleton is achieved from the arylsilane cyclization products.