An Analysis of Visibility and Anatomic Variations of Mandibular Canal in Digital Panoramic Radiographs of Dentulous and Edentulous Patients in Northern Iran Populations.
Insufficient information about the anatomical positions and structure of mandibular canal provokes unwanted damage to this important structure of mandible. The aim of this study was to determine the visibility and anatomical variations of mandibular canal in digital panoramic radiographs of dentulous and edentulous patients in a sample of Iranian population. In this retrospective-analytical research, 249 digital panoramic radiographs in dentulous group and 126 in edentulous group were studied by an expert oral and maxillofacial radiologist. In both groups, the visibility of canal borders in anterior, middle, and posterior areas were examined. In dentulous group, the distance between the canal and apex of the first and second molars were measured. Canal-to-alveolar crest distance and lower mandibular border was measured in three different points for both groups. Finally, the upper-lower positions of canals were determined. In both groups, most visibility occurred in 1/3 of posterior and the least visibility was detected in 1/3 of anterior, with the intermediate being the most visible part (Type 2). There was no significant difference between the left and right sides in all cases. In dentulous group, no correlation was found between the visibility, age, and gender (p> 0.05); however, canal position was related to gender (p= 0.03 and p= 0.04 in right and left sides, respectively). High position was more frequent in females and intermediate position was more common in males. In edentulous group, no correlation was found between age, gender, and canal position (p> 0.05). The most visibility of mandibular canal was in its third posterior and the least was in its third anterior part. Although the middle position of canal was more frequently visible than the high position in this study, it does not refute the possibility of damaging the mandibular canal in critical surgeries.


Anaerobic biotransformation of sulfonated anthraquinones by Pseudomonas nitroreducens WA and the fate of the sulfonic acid group in the presence of nitrate.
The presence of the sulfonic acid group in sulfonated anthraquinones (SAs) resulted in the difficulty in the mineralization of anthraquinone ring. Little information is available on the removal pathway of the sulfonic acid group of SAs under aerobic/anaerobic conditions. Herein, sodium 1-aminoanthraquinone-2-sulfonate (ASA-2) was used as an important intermediate of SAs. A novel Pseudomonas nitroreducens WA capable of ASA-2 desulfonation was isolated from the Reactive Blue 19-degrading consortium WRB. Anaerobic desulfonation efficiency of 0.165 mM ASA-2 by strain WA reached 99% in 36 h at pH 7.5 and 35 ℃ using glucose as an electron donor. Further analysis showed that ASA-2 as an electron acceptor could be anaerobically transformed into 1-aminoanthraquinone and sulfite via the cleavage of C-S bond. Strain WA could also desulfonate sodium 1-amino-4-bromoanthraquinone-2-sulfonate and sodium anthraquinone-2-sulfonate. Under denitrification conditions, the formed sulfite could be oxidized to sulfate by nitrite via a chemical reaction, which was beneficial for nitrite removal. This phenomenon was observed in consortium WRB-amended system. Moreover, the consortium WRB could reduce the formed sulfite to sulfide due to the presence of Desulfovibrio. These results provide a theoretical basis for the anaerobic biodesulfonation of SAs along with nitrate removal and support for the development of sulfite-based biotechnology.


Discrepancy in divergence of the mitochondrial and nuclear genomes of Drosophila teissieri and Drosophila yakuba.
Restriction sites were compared in the mitochondrial DNA (mtDNA) molecules from representatives of two closely related species of fruit flies: nine strains of Drosophila teissieri and eight strains of Drosophila yakuba. Nucleotide diversities among D. teissieri strains and among D. yakuba strains were 0.07% and 0.03%, respectively, and the nucleotide distance between the species was 0.22%. Also determined was the nucleotide sequence of a 2305-nucleotide pair (ntp) segment of the mtDNA molecule of D. teissieri that contains the noncoding adenine + thymine (A + T)-rich region (1091 ntp) as well as the genes for the mitochondrial small-subunit rRNA, tRNA(f-met), tRNA(gln), and tRNA(ile), and portions of the ND2 and tRNA(Val) genes. This sequence differs from the corresponding segment of the D. yakuba mtDNA by base substitutions at 0.1% and 0.8% of the positions in the coding and noncoding regions, respectively. The higher divergence due to base substitutions in the A + T-rich region is accompanied by a greater number of insertions/deletions than in the coding regions. From alignment of the D. teissieri A + T-rich sequence with those of D. yakuba and Drosophila virilis, it appears that the 40% of this sequence that lies adjacent to the tRNA(ile) gene has been highly conserved. Divergence between the entire D. teissieri and D. yakuba mtDNA molecules, estimated from the sequences, was 0.3%; this value is close to the value (0.22%) obtained from the restriction analysis, but 10 times lower than the value estimated from published DNA hybridization results.(ABSTRACT TRUNCATED AT 250 WORDS)


[Influence of the pathogenetic variant of uterine cancer on the dynamics of prolactin secretion in the early and late postoperative periods].
In early postoperative period, patients with uterine carcinoma of pathogenetic types I and II developed hyperprolactinemia with similar frequency. However, elevation of prolactin concentration was found to vary with pathogenetic type. For type I endometrial carcinoma, prolactin level on postoperative days 1-5 was twice those registered in type II tumor. Later, prolactin levels returned to normal.


Topographic monitoring of a middle estuary mudflat, Humber estuary, UK--anthropogenic impacts and natural variation.
Annual topographic surveys were carried out at the Saltend mudflat (Humber estuary, UK) between 1998 and 2006. These surveys formed part of an ongoing monitoring programme to examine the potential effects on the mudflat topography of the construction and operation of a waste water treatment works (WwTW) development by Yorkshire Water. Of particular concern was the potential disruption to the sedimentological regime within the special protection area (SPA) and candidate special area of conservation (cSAC) which could affect the invertebrate communities and ornithological functioning of the site. In addition to the development of the WwTW located to the extreme north-west of the site, a port extension removing 10ha of the Saltend intertidal mudflat (outside the SPA but immediately south east of the WwTW) also occurred between 1999 and 2006. Minimal change was noted across the site following the construction and operation of the WwTW between 1998 and 2000. However, the construction of the bund in closer proximity to the SPA and cSAC masked any potential impact the WwTW could have had across the site after 2000. Profiles and contour mapping indicate that significant mudflat accretion occurred in the immediate area of the bund, with a general increase recorded across the western section of the site since 2000. In contrast the alternations to channel planform and subsequent rapid accretion of the mudflat to the east of the jetty, being a significant distance from the developments, are attributed to natural cyclical changes.


Joint tenderness and swelling in biologic-treated inflammatory arthritis patients - a tricky trade off?
To compare the pattern of joint responses in patients with rheumatoid arthritis and psoriatic arthritis treated with TNF inhibitor (TNFi) therapy. A total of 182 PsA/Rheumatoid arthritis (RA) patients attending the rheumatology unit of a tertiary referral centre in Ireland were recruited and prospectively followed up by the attendant rheumatologists. Clinical progress of the patients was noted at baseline and 6 months after starting TNFi therapy. A total of 114 RA and 68 PsA patients were assessed; 20% of the patients had one of either tender joints or swollen joints after 6 months of therapy. Rheumatoid arthritis patients had a significantly higher proportion of non-tender swollen joints compared with PsA patients, whereas PsA patients had a higher proportion of tender non-swollen joints (p < 0.05). Residual joint swelling was found more commonly in RA patients than in PsA patients following TNFi therapy, whereas residual tender joints occurred more frequently in PsA; this may reflect enthesiopathy or periostitis.


Neospora caninum: functional inhibition of protein disulfide isomerase by the broad-spectrum anti-parasitic drug nitazoxanide and other thiazolides.
Nitazoxanide (NTZ) and several NTZ-derivatives (thiazolides) have been shown to exhibit considerable anti-Neospora caninum tachyzoite activity in vitro. We coupled tizoxanide (TIZ), the deacetylated metabolite, to epoxy-agarose-resin and performed affinity chromatography with N. caninum tachyzoite extracts. Two main protein bands of 52 and 43kDa were isolated. The 52kDa protein was readily recognized by antibodies directed against NcPDI, and mass spectrometry confirmed its identity. Poly-histidine-tagged NcPDI-cDNA was expressed in Escherichia coli and recombinant NcPDI (recNcPDI) was purified by Co2+-affinity chromatography. By applying an enzyme assay based on the measurement of insulin crosslinking activity, recNcPDI exhibited properties reminiscent for PDIs, and its activity was impaired upon the addition of classical PDI inhibitors such as bacitracin (1-2mM), para-chloromercuribenzoic acid (0.1-1mM) and tocinoic acid (0.1-1mM). RecNcPDI-mediated insulin crosslinking was inhibited by NTZ (5-100 microM) in a dose-dependent manner. In addition, the enzymatic activity of recNcPDI was inhibited by those thiazolides that also affected parasite proliferation. Thus, thiazolides readily interfere with NcPDI, and possibly also with PDIs from other microorganisms susceptible to thiazolides.


[Comparison of radiation exposure in common hepatic interventions : A retrospective analysis of DeGIR registry data].
Transcatheter arterial chemoembolization (TACE) and biliary interventions are common procedures. In this retrospective study, the radiation exposure of patients undergoing hepatic intervention will be analyzed and compared depending on the type and objective of the intervention. This is an analysis of 7003 data sets of performed TACEs and biliary interventions from the DeGIR registry for the years 2016, 2017, and 2018. The dose area product (DAP), fluoroscopy time (FT), type of intervention, and anatomically defined target were recorded. Data with documented radiation doses were available for 4985 TACEs and for 2018 biliary interventions. For biliary interventions the median DAP was 2594 (interquartile range [IQR] = 1174-5858) cGycm2. For TACE, the median DAP was 11,632 [IQR = 5530-22,800] cGycm2 and significantly higher compared to biliary interventions (p < 0.0001). Biliary interventions with the highest DAP take place at the common hepatic duct; procedures with the longest FT were registered at the hepatic duct bifurcation. The individual radiation exposure during liver interventions is less dependent of the complexity of the procedure or the fluoroscopy time, but rather on the type of intervention and the anatomic target. The presented data can help to approximately estimate the radiation exposure in advance when planning an intervention.


Copper speciation and microbial activity in long-term contaminated soils.
Most soil quality guidelines do not distinguish among the various forms of metals in soils; insoluble, nonreactive, and nonbioavailable forms are deemed as hazardous as highly soluble, reactive, and toxic forms. The objective of this study was to better understand the long-term effects of copper on microorganisms in relation to its chemical speciation in the soil environment. Carbon mineralization processes and the global structure of different microbial communities (fungi, eubacteria, actinomycetes) are still affected after more than 50 years of copper contamination in 20 soils sampled from two different agricultural sites. The microbial respiration lag period (LP) preceding the beginning of mineralization process increases with the level of soil copper contamination and is not significantly affected by other environmental factors such as soil pH and soil organic matter (SOM) content. The total copper concentration showed the best correlation with the LP when each site is considered separately. However, when considering the whole set of data, soil solution free Cu2+ activity (pCu2+) is the best predictor of Cu toxicity determined by LP (quite likely because pCu2+ integrates the soil physicochemical variability). The maximum mineralization rate (MMR), even if well correlated with the pCu2+, appears not to be a good biomonitor of copper contamination in soils since it is highly sensitive to soil characteristics such as SOM content. This study emphasizes the importance of the physicochemical properties of the environment on soil heavy metal toxicity and on soil toxicological measurements. These properties must be characterized in soil toxicological studies with respect to (1) their interactions with heavy metals, and (2) their direct impact on the selected biological test. The measurement of pCu2+ to characterize the level of soil contamination and of lag period as a bioindicator of metal effects in the soil are recognized as useful tools for the evaluation of the biological quality of soils.


Injections of excitatory amino acid antagonists into the median raphe nucleus produce hippocampal theta rhythm in the urethane-anesthetized rat.
The median raphe nucleus (MR) exerts a pronounced desynchronizing influence on the hippocampal EEG. MR stimulation disrupts theta, while MR lesions produce constant uninterrupted theta. The MR receives pronounced excitatory amino acid (EAA)-containing afferents that have been implicated in several MR-mediated behaviors. The present study examined the effects on the hippocampal EEG of MR injections of the following EAA antagonists in the urethane-anesthetized rat: 2-amino-7-phosphonoheptanoate (AP-7), dizocilpine maleate (MK-801), and gamma-glutamyl-aminomethylsulfonic acid (GAMS). MR injections of the competitive (AP-7) and non-competitive (MK-801) N-methyl-D-aspartic acid (NMDA) receptor antagonists produced theta at short latencies (2.86 min; 4.02 min, respectively) and for long durations (116.1 min; 66.8 min, respectively). It was further shown that the theta-eliciting effects of AP-7 injections could be reliably and temporarily reversed with MR injections of NMDA. MR injections of the kainate/quisqualate receptor antagonist (GAMS) also produced theta at relatively short latencies (6.5 min) and for long durations (60.5 min) indicating that EAA effects on the MR are not NMDA receptor specific. Injections of each of the foregoing EAA antagonists into regions of the brainstem adjacent to the MR including the dorsal raphe nucleus and the medullary or pontine reticular formation generated theta at very long latencies or were without effect. The present findings indicate EAA afferents to the MR normally exert an excitatory influence on the MR in its desynchronization of the hippocampal EEG, whereas the removal of EAA inputs to MR produces the opposite: a reduction of MR activity and hence the elicitation of theta.(ABSTRACT TRUNCATED AT 250 WORDS)


Pedunculated and telangiectatic merkel cell carcinoma: an unusual clinical presentation.
Merkel cell carcinoma (MCC) is an uncommon aggressive neuroendocrine tumor of the skin that classically presents on chronic sun-damaged skin as a skin-colored, red or violaceous, firm and nontender papule or nodule with a smooth and shiny surface. Ulcerations can be observed very seldom and only in very advanced lesions. We present a unique case of a MCC presenting with two unusual clinical features: The Telangiectatic surface and the pedunculated aspect.


Anatomical basis of the risk of injury to the right laryngeal recurrent nerve during thoracic surgery.
Despite the intrathoracic part being short, the right laryngeal recurrent nerve is often injured during thoracic surgery. The aim of this cadaver study was to understand the mechanisms of right laryngeal recurrent nerve injuries during thoracic surgery and to describe anatomical landmarks for its preservation. Dissections were performed on 10 fresh human cadavers. A right anterolateral thoracic wall segment was removed, preserving the first rib. Dissections were carried out to identify the following structures: first rib, esophagus, trachea, right main bronchus, right brachiocephalic and subclavian vessels, azygos vein, phrenic nerve, vagus nerve, and right laryngeal recurrent nerve. The distance between the origin of the right laryngeal recurrent nerve and its adjacent structures was assessed. Moderate traction of the thoracic part of the vagus nerve resulted in a downward translation of the right laryngeal recurrent nerve's origin. In such conditions, the right laryngeal recurrent nerve's origin was distant of 14.8 mm (±2.89 mm) from the subclavian artery. Intraoperative incidence of right laryngeal recurrent nerve direct injury could be decreased by understanding the detailed course of its intrathoracic part. Moreover, traction on the intrathoracic part of the right vagus nerve may result in indirect lesions of the right laryngeal recurrent nerve: stretch induced lesions and nerve vasculature's lesions.


Neuroprotective effect of meglumine cyclic adenylate against ischemia/reperfusion injury via STAT3-Ser727 phosphorylation.
Ischemia/reperfusion can induce neuronal apoptosis in the brain and lead to function deficits. The activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase (PKA) is neuroprotective against transient cerebral ischemia. The neuroprotective mechanisms of PKA mainly involve the regulation of gene transcription via the PKA/CREB pathway. The present study aims to investigate the neuroprotective effect of meglumine cyclic adenylate, an activator of PKA, under a rat model of global cerebral ischemia/reperfusion and to reveal the underlying mechanism involving signal transducer and activator of transcription 3 (STAT3)-Ser727 phosphorylation and mitochondrion modulation. Male Sprague-Dawley rats were subjected to 15 min global cerebral ischemia, and meglumine cyclic adenylate was treated through tail intravenous injection 30 min before ischemia. Cresyl violet staining was used to evaluate neuron injury at 5 d of reperfusion. Western blotting was used to detect p-Ser727-STAT3, total STAT3, cytochrome c (Cyt c) and active caspase-3 in the tissues of hippocampal CA1 region at 6 h of reperfusion. STAT3-S727A was overexpressed in HT22 cells to reveal the significance of STAT3-Ser727 phosphorylation in the neuroprotective effect of meglumine cyclic adenylate. Pretreatment with meglumine cyclic adenylate not only significantly ameliorated neuron loss in CA1 region after global cerebral ischemia but also enhanced STAT3-Ser727 phosphorylation, increased mitochondrial STAT3, and decreased cytosolic Cyt c and active caspase-3. Overexpression of STAT3-S727A in HT22 cells eliminated meglumine cyclic adenylate-induced increase of p-Ser727-STAT3, mitochondrial STAT3, cytosolic Cyt c and active caspase-3. Meglumine cyclic adenylate protects neurons against ischemia/reperfusion injury via promoting p-Ser727-STAT3-associated mitochondrion modulation and inhibiting apoptosis pathway.


Idiopathic generalized epilepsy of late onset.
Most idiopathic generalized epilepsies have an onset in childhood or adolescence, with a moderate second incidence peak in the presenium predominantly in women. This study addressed the question of a later onset. The available literature and the records of four personal data sets (two prospective incidence surveys of epileptic seizures, one prevalence study of epilepsy, and one clinical series of individuals with epilepsy) were screened for patients who had experienced a first generalized convulsive seizure with bilateral spike-wave complexes on EEG after 60 years of age. Reports of first idiopathic generalized tonic-clonic seizures occurring after age 60 were extremely rare and none was found in our four cohorts regardless of the methodology involved. Only five case reports were found, all involving a woman. Two had a family history of seizure disorders and two had had at least one seizure earlier in life. Idiopathic generalized epilepsy of late onset, if this condition actually exists, is likely to be the consequence of a genetic predisposition triggered by acquired epileptogenic factors.


Prognostic value of myocardial injury following transcatheter aortic valve implantation.
There is a lack of clarity concerning the clinical implications of myocardial injury occurring after transcatheter aortic valve implantation (TAVI) procedures. The aim of this study was to determine the incidence, degree, and timing of myocardial injury associated with TAVI procedures and to evaluate its 1-year prognostic value. Among 68 consecutive patients (mean age 80.9 ± 6.4 years) treated with TAVI, 3 patients who died within 24 hours, precluding cardiac biomarker measurements, and 3 patients with major procedural complications were excluded. Cardiac troponin I, creatine kinase-MB, and creatinine levels were determined at baseline and 6, 12, 24, 48, and 72 hours after TAVI. All complications were defined according to the Valve Academic Research Consortium. Myocardial injury was observed in all patients (n = 62), as determined by an increase in cardiac troponin I (median peak at 12 hours 3.8 μg/L, interquartile range 1.8 to 25.67), and a higher degree of myocardial injury was observed in patients (n = 9) who developed acute kidney injury (AKI) (p = 0.026). Periprocedural myocardial infarction was not found. At 1-year follow-up, 5 patients had died, and 7 patients had been hospitalized for heart failure. The development of AKI, not the degree of peak cardiac troponin I (p = 0.348), was identified as the only strong independent predictor of 1-year mortality from any cause (including heart failure) after TAVI (hazard ratio 4.74, 95% confidence interval 1.12 to 20.03, p = 0.034). In conclusion, TAVI was systematically associated with myocardial injury, occurring with a higher degree in patients who developed AKI. However, the simultaneous development of AKI occurring after TAVI is the strongest predictor of 1-year mortality.


Effects of production conditions on yield and physicochemical properties of biochars produced from rice husk and oil palm empty fruit bunches.
Biochar is the bio-solid material produced by pyrolysis. The biochar properties are controlled by feedstock and pyrolysis variables. In this study, the impacts of these production variables on biochar yield and physicochemical properties including pH, cation exchange capacity (CEC), total organic carbon (TOC) content, surface area, and pore volume and size were investigated. Rice husk (RH) and oil palm empty fruit bunches (EFB) were used as biomass. The biochars were produced at temperature range of 300 to 700 °C, heating rate of 3 to 10 °C/min and retention time of 1 to 3 h. The pyrolysis conditions were optimized using response surface methodology (RSM) technique to maximize the values of the responses. Analysis of variance (ANOVA) of the results demonstrated that the data fitted well to the linear and quadratic equations. Temperature was found to be the most effective parameter on the responses followed by retention time and heating rate, sequentially. CEC, TOC, surface area, and pore characteristics were evaluated as biochar properties determining their sorption potential. The optimum conditions for the maximum values of the properties were temperatures of 700 and 493.44 °C and time of 3 and 1 h for RH and EFB biochars, respectively. Heating rate at 3 °C/min was found to be the best rate for both biochars. The structure of EFB biomass was more sensitive to heating than rice husk. The biomass type and the production variables were demonstrated as the direct effective factors on biochar yield and physicochemical properties.


Rural-urban migration and sickness/health care behaviour: a study of Eastern Nigeria.
This study is an effort to assess whether the concept of 'migration personality' applies in the context of Eastern Nigerian urban dwellers. Sickness and health care behaviour is compared between two groups--migrant urban households living in Uyo and Calabar and non-migrant rural households living in Ediene and Ibiono. The respondents' conceptions and perceptions of illness, disease and health as well as the medical services frequently used are analysed. The findings tend to confirm the existence of marked differences in disease beliefs and related health care behaviour in the two groups. These differences are crystallized along residency, socio-economic, age and income characteristics. The implication of the study is that even though it is not possible meanwhile to determine whether migration is an independent or intervening variable, or one of several other and inter-related variables, the fact that rural-urban migrants are so prone to modern medical practices, raises the desirability of using them as a target population for primary acceptance of modern medical programmes such as those concerning family planning, child nutrition and health.


Histamine release into tracheal lumen and bronchial reactivity. Effect of compound 48/80 administered by different routes in various doses on histamine release and bronchial reactivity.
The influence of tracheal lavage with compound 48/80 on the bronchial response to challenge with ACH and AE was studied in 24 animals. Furthermore, the effect of i.v. administration of 48/80 was compared to its administration into the tracheal lumen. No increased histamine liberation was detected in the tracheal fluid after lavage with 48/80, nor was an influence on the bronchial response observed. These observations were the same as those described for tracheal lavage with water. The same amounts of this secretagogue induced, after i.v. administration, a high histamine release which correlates significantly with blood pressure decrease.


Distinctive immunostaining of claudin-4 in spiradenomas.
The intercellular bridges are essential structures in maintaining the histologic organization of the epithelium, while providing a very efficient way to exchange molecules between cells and transduction of the cell-to-cell and matrix-to-cell signals. Derangement in those important structures' physical integrity and/or function, which can be assessed by the presence or absence of several intercellular bridge proteins including claudin-4, E-cadherin, and β-catenin, was found to be related to several phenomena in the path to the neoplastic transformation. However, these proteins have not been studied in the wide variety of the skin neoplasms, in detail. Herein, we immunohistochemically assessed the expression patterns of these 3 intercellular bridge proteins on a total of 86 epidermal and eccrine adnexal tumors including basal cell carcinoma, squamous cell carcinoma, poroma, spiradenoma, syringoma, and hidradenoma. We observed a selective and distinct claudin-4 expression in the ductal-type cells of all cases of spiradenomas. Similarly, in the poromas, syringomas, and hidradenomas, claudin-4 was only positive in the luminal cells of microcystic structures, although not as conspicuous as in the spiradenomas. On the other hand, E-cadherin and β-catenin were positive in almost all types of the tumors, in a way which was not contributory to differentiate from each other. In conclusion, we think that claudin-4 can be helpful at least in making a reliable differential diagnosis of spiradenoma when overlapping morphologic features do not allow to further subclassification in the overwhelming variety of the adnexal tumors.


Gut mucosal DAMPs in IBD: from mechanisms to therapeutic implications.
Endogenous damage-associated molecular patterns (DAMPs) are released during tissue damage and have increasingly recognized roles in the etiology of many human diseases. The inflammatory bowel diseases (IBD), ulcerative colitis (UC) and Crohn's disease (CD), are immune-mediated conditions where high levels of DAMPs are observed. DAMPs such as calprotectin (S100A8/9) have an established clinical role as a biomarker in IBD. In this review, we use IBD as an archetypal common chronic inflammatory disease to focus on the conceptual and evidential importance of DAMPs in pathogenesis and why DAMPs represent an entirely new class of targets for clinical translation.


Treatment of severe COVID-19 with human umbilical cord mesenchymal stem cells.
COVID-19 is a highly infectious respiratory disease. No therapeutics have yet been proven effective for treating severe COVID-19. To determine whether human umbilical cord mesenchymal stem cell infusion may be effective and safe for the treatment of severe COVID-19. Patients with severe COVID-19 were randomly divided into 2 groups: the standard treatment group and the standard treatment plus hUC-MSC infusion group. The incidence of progression from severe to critical illness, 28-day mortality, clinical symptom improvement, time to clinical symptom improvement, hematologic indicators including C-reactive protein, lymphocyte number, and interleukin 6, and imaging changes were observed and compared between the two groups. The incidence of progression from severe to critical illness and the 28-day mortality rate were 0 in the hUC-MSC treatment group, while 4 patients in the control group deteriorated to critical condition and received invasive ventilation; 3 of them died, and the 28-day mortality rate was 10.34%. In the hUC-MSC treatment group, the time to clinical improvement was shorter than that in the control group. Clinical symptoms of weakness and fatigue, shortness of breath, and low oxygen saturation obviously improved beginning on the third day of stem cell infusion and reached a significant difference on day 7. CRP and IL-6 levels were significantly lower from day 3 of infusion, the time for the lymphocyte count to return to the normal range was significantly faster, and lung inflammation absorption was significantly shorter on CT imaging in the hUC-MSC group than in the control group. Intravenous transplantation of hUC-MSCs is a safe and effective method that can be considered a salvage and priority treatment option for severe COVID-19. Chinese Clinical Trial Registration; ChiCTR2000031494; Registered on 2 April 2020; http:// www.medresman.org.


Exhaled breath condensate isoprostanes are elevated in patients with acute lung injury or ARDS.
Oxidant stress is a purported mechanism of tissue damage in patients with ARDS and acute lung injury (ALI). Isoprostanes, prostanoid compounds primarily formed nonenzymatically via lipid peroxidation, are precise markers of in vivo oxidant stress. Plasma levels of metabolites of 8-iso-prostaglandin-F2alpha (8-iso-PGF2alpha) correlate with outcome in patients with ARDS. To examine exhaled breath condensate levels of 8-iso-PGF2alpha as a noninvasive quantification of pulmonary oxidant stress in patients with, or at risk for, ARDS/ALI. Breath condensate was collected from 22 patients with, or at risk for, ARDS/ALI by placing Tygon tubing submerged in an ice bath in line with the expiratory limb of the ventilator circuit. Ten patients without lung disease, who were intubated while undergoing minor surgical procedures, served as control subjects. Between 1 and 3 mL of condensate was collected over a 30- to 60-min period, then immediately frozen and stored at -70 degrees C until analysis. The 8-iso-PGF2alpha was purified and derivatized, then quantified by stable isotope dilution in conjunction with gas chromatography/mass spectrometry. The mean level of exhaled 8-iso-PGF2alpha in the patients with ALI/ARDS, 87+/-28 pg/mL, was significantly higher than the mean in the normal group, 7+/-4 pg/mL (p = 0.007). The 8-iso-PGF2alpha levels were greater than two standard deviations above the mean of the normal group in 12 of 22 patients with or at risk for ARDS/ALI. These results provide further evidence that lipid peroxidation does occur in patients with ARDS/ALI. The measurement of exhaled isoprostanes provides a novel, noninvasive method to quantify oxidant stress in such patients.


A multilocular discal cyst extending from the spinal canal to the extraforaminal region: A case report.
Lumbar discal cysts are intraspinal extradural cysts communicating with the intervertebral disc. The usual location and morphology are in the caudal ventrolateral epidural space of the spinal canal, without extension to the neural foramen or crossing the midline and described as a well-defined homogeneous oval or spherical cyst on low and high signal intensities observed in lumbar lesions on T1- and T2-weighted magnetic resonance imaging, respectively. We report an unusual lumbar discal cyst in terms of the lesion location and morphology. A 33-year-old-man presented with lower back and right anterior thigh pain. Magnetic resonance imaging revealed multilocular cystic lesions in the cranial ventrolateral epidural space at L2-L3 with low and high signal intensities on T1- and T2-weighted magnetic resonance imaging, respectively. We performed a full-endoscopic transforaminal cystectomy under general anesthesia. Lumbar discal cysts should be considered a differential diagnosis for multilocular intraspinal cystic lesion.


Targeted Isolation of Dolabellane Diterpenoids from the Soft Coral Clavularia viridis Using Molecular Networking.
LC-MS/MS-based molecular networking annotation coupled 1H NMR detection allowed the depiction of the soft coral Clavularia viridis to produce a profile of dolabellane-type diterpenoids. Chromatographic separation of the EtOAc fraction resulted in the isolation of 12 undescribed dolabellane-type diterpenoids, namely, clavirolides J-U (1-12). Their structures were characterized by the extensive analysis of the spectroscopic data, including the calculated ECD and X-ray diffraction for the configurational assignments. Clavirolides J-K are characterized by a 1,11- and 5,9-fused tricyclic tetradecane scaffold fused with a α,β-unsaturated-δ-lactone, and clavirolide L possesses a 1,11- and 3,5-fused tricyclic tetradecane scaffold, which extend the dolabellane-type scaffolds. Clavirolides L and G showed significant inhibition against HIV-1 without RT enzyme inhibition, providing additional non-nucleosides with different mechanisms from efavirenz.


Ethnic differences in extreme obesity.
A nationwide representative survey of New Zealand schoolchildren showed a 2.7% incidence of extreme obesity (versus 4% in the United States) but revealed worrying ethnic differences in prevalence. Prevalence percentages (95% CI) were 0.8 (0.4 to 1.9), 5.1 (3.6 to 7.1), and 10.9 (8.9 to 13.3) in New Zealand European, Māori, and Pacific Island groups, respectively. These findings warrant remedial action.


Cytomics and drug discovery.
Pharmaceutical companies try to develop new drugs that have a high success rate of reaching the market. However, current disease models lack a strong correlation to clinical reality, because of the underestimation of the complexity and variability of clinical disease processes. This leads to high attrition rates late in drug development and soaring costs. Improvement of disease models is an important issue to reduce the high attrition rates in drug development. Using cell-based disease models, which should take into account the molecular diversity of the human cytome, will improve the predictive value of drug discovery.


Effect of face mask on topographic corneal parameters in healthy individuals.
To evaluate whether the use of masks has an effect on the measurement of corneal topographic parameters. A study including healthy patients with no previous ocular diseases or surgeries was conducted. Corneal topography was evaluated with an elevation topography Pentacam Scheimpflug. Four measurements were taken: two measurements with face mask and another two measurements after 10 min without wearing the face mask. The following parameters were evaluated: anterior topographic flat meridian (K1), anterior topographic steepest meridian (K2), mean keratometry (Km) and maximum keratometric point (Kmax). Thirty-five eyes of thirty-five healthy individuals were included; with a mean age of 33.5 ± 13.8 years (range 24-66) and 26 (74%) being female. Mean time with face-mask was 3.8 ± 2.2 h (range 1-8). No differences in mean K1, K2, Km and Kmax with and without face-mask were noted (paired t-test, all, p > 0.05). Intraclass correlation coefficients (ICC) were excellent for all four analyzed parameters (ICC > 0.914), although they were lower when measurements with face-mask were considered. Although tear film alterations with the use of face-mask have been described in the literature, no significant differences can be noted in topographic variables.


The role of the adrenergic innervation to the pancreatic islets in the control of insulin release during exercise in man.
The normal depression of plasma insulin concentration during exercise has been ascribed to adrenergic inhibition of insulin release and the role of humoral catecholamines in this hormonal adjustment has repeatedly been stressed. In the present study this contention has been investigated in 6 bilaterally adrenalectomized patients and in 6 sex- and age-matched controls who undertook exercise on an ergometer until they were exhausted. No differences were observed in any cardiovascular or metabolic adjustments between the two groups during strenous exercise. Mean plasma insulin concentration fell by about 50% in both groups. Phentolamine effectively abolished the fall in plasma insulin concentration during exercise in 2 adrenalectomized patients. The results suggest that the adrenergic nerves that supply the B-cells have a functional role in man during exercise.


The association between MRI brain volumes and computerized cognitive scores of people with multiple sclerosis.
Computerized cognitive assessment facilitates the incorporation of multi-domain cognitive monitoring into routine clinical care. The predictive validity of computerized cognitive assessment among people with multiple sclerosis (PwMS) has scarcely been investigated. To explore the associations between brain volumes and cognitive scores from a computerized cognitive assessment battery (CAB, NeuroTrax) among PwMS. PwMS were evaluated with the CAB and underwent brain MRI within 40 days. Cognitive assessment yielded age- and education-adjusted scores in 9 cognitive domains: memory, executive function, attention, information processing speed, visual spatial, verbal function, motor skills, problem solving, and working memory. The global cognitive score (GCS) is the average of all domain scores. MRI brain and lesion volumes were assessed with icobrain ms, a fully automated tissue and lesion segmentation and quantification software. 91 PwMS were included [Age: 52.1 ± 11.7 years, 64 (70%) female, EDSS: 3.4 ± 2.0, 79 (87%) with a relapsing remitting course]. Significant correlations were found between the GCS and whole brain, white matter, grey matter, thalamic, lateral ventricles, hippocampal and lesion volumes (Correlation coefficients: 0.46, 0.40, 0.25, 0.42, -0.36, 0.21, -0.3, respectively). Regression analysis revealed that lateral ventricles and thalamic volumes were the most consistent predictors of all cognitive domain scores. Computerized cognitive scores were significantly associated with quantified MRI. These findings support the predictive validity of multi-domain computerized cognitive assessment for people with multiple sclerosis.


Nerve growth factor supply for sensory neurons: site of origin and competition with the sympathetic nervous system.
Nerve growth factor (NGF) levels in the sensory nervous system were measured by a highly sensitive two-site enzyme immunoassay for NGF. Dorsal root ganglia and the adjacent spinal nerves contained 2.8 +/- 0.3 and 1.7 +/- 0.4 ng NGF/g wet wt., respectively, whereas no NGF was detectable in dorsal roots and spinal cord (less than 0.05 ng NGF/g wet wt.). It is concluded that sensory neurons are supplied with NGF exclusively from their peripheral and not from their central field of projection. Two days after treatment with 6-hydroxydopamine, which destroys sympathetic nerve terminals and thereby prevents the removal of NGF by sympathetic neurons, the NGF content of dorsal root ganglia and trigeminal ganglia increased to 285% and 161% of control, respectively. This indicates that in peripheral target tissues sensory and sympathetic neurons compete for NGF.


Optimization of anti-proliferative activity using a screening approach with a series of bis-heterocyclic G-quadruplex ligands.
Using a phenotypic screening and SAR optimization approach, a phenyl-bis-oxazole derivative has been identified with anti-proliferative activity, optimized with the use of a panel of cancer cell lines. The lead compound was synthesized by means of a short and effective two-step synthesis using Pd-catalyzed direct arylation. The compound stabilizes several quadruplex DNA sequences including a human telomeric DNA and one from the promoter of the HSP90 gene, although the structure-activity relationships of the series are not obviously related to the quadruplex binding.


Survival Prospects and Circumstances of Death in Contemporary Adult Congenital Heart Disease Patients Under Follow-Up at a Large Tertiary Centre.
Adult congenital heart disease (ACHD) patients have ongoing morbidity and reduced long-term survival. Recently, the importance of specialized follow-up at tertiary ACHD centers has been highlighted. We aimed to assess survival prospects and clarify causes of death in a large cohort of patients at a single, tertiary center. We included 6969 adult patients (age 29.9 ± 15.4 years) under follow-up at our institution between 1991 and 2013. Causes of death were ascertained from official death certificates. Survival was compared with the expected survival in the general age- and sex-matched population, and standardized mortality rates were calculated. Over a median follow-up time of 9.1 years (interquartile range, 5.2-14.5), 524 patients died. Leading causes of death were chronic heart failure (42%), pneumonia (10%), sudden-cardiac death (7%), cancer (6%), and hemorrhage (5%), whereas perioperative mortality was comparatively low. Isolated simple defects exhibited mortality rates similar to those in the general population, whereas patients with Eisenmenger syndrome, complex congenital heart disease, and Fontan physiology had much poorer long-term survival (P<0.0001 for all). The probability of cardiac death decreased with increasing patient's age, whereas the proportion of patients dying from noncardiac causes, such as cancer, increased. ACHD patients continue to be afflicted by increased mortality in comparison with the general population as they grow older. Highest mortality rates were observed among patients with complex ACHD, Fontan physiology, and Eisenmenger syndrome. Our data provide an overview over causes of mortality and especially the spectrum of noncardiac causes of death in contemporary ACHD patients.


Is there gender bias in research fellowships awarded by the NHMRC?
To assess whether there is gender bias in the allocation of research fellowships granted by the Research Fellowships Committee of the National Health and Medical Research Council. Anonymous data from applications for a research fellowship from 1994 to 1997. More men than women apply for research fellowships (sex ratio, 2.5:1), but there is no difference in the proportion of male or female applicants who succeed in their application. Among new applicants, men tend to apply for a higher level of fellowship than women. Lack of data about the numbers of eligible men and women means that we cannot draw conclusions about self-selection biases among potential applicants. However, the selection procedures of the Committee appear to be unbiased. The gender of applicants does not influence the outcome of their application.


Ex vivo expansion of polyclonal and antigen-specific cytotoxic T lymphocytes by artificial APCs expressing ligands for the T-cell receptor, CD28 and 4-1BB.
The ex vivo priming and expansion of human cytotoxic T lymphocytes (CTLs) has potential for use in immunotherapy applications for cancer and infectious diseases. To overcome the difficulty in obtaining sufficient numbers of CTLs, we have developed artificial antigen-presenting cells (aAPCs) expressing ligands for the T-cell receptor (TCR) and the CD28 and 4-1BB co-stimulatory surface molecules. These aAPCs reproducibly activate and rapidly expand polyclonal or antigen-specific CD8(+) T cells. The starting repertoire of CD8+ T cells was preserved during culture. Furthermore, apoptosis of cultured CD8(+) T cells was diminished by this approach. This approach may have important therapeutic implications for adoptive immunotherapy.


Cognition in older offenders in North Rhine-Westphalia: A comparison of prisoners and patients in forensic psychiatry hospitals.
The number of elderly delinquent individuals living in prisons and forensic hospitals is increasing. For both settings, complex needs have been described for the elderly related to age-related changes and frequent somatic disorders as well as mental disorders, primarily depressive symptoms.. One of the biggest challenges are cognitive impairments which have been described for both groups, probably not least due to frequent risk factors (e.g., substance abuse, depressive symptoms). Given that the group of forensic patients has a manifest mental illness, which is usually treated with psychopharmaceuticals, the question arises as to what extent cognitive deficits are more frequent here. For both groups, the detection of cognitive deficits with regard to therapy and release planning is of relevance. In sum, studies on cognitive function in both populations are rare, and the results are hard to compare due to different instruments to assess cognition. Sociodemographic, health-, and incarceration-related data were collected as well as neuropsychological functions using established instruments to evaluate global cognitive functioning (Mini-Mental State Examination [MMSE], DemTect), executive function (Frontal Assessment Battery [FAB], and Trail Making Test [TMT]). In the final sample, 57 prisoners and 34 forensic inpatients from North Rhine Westphalia, Germany being 60 years and older were included. The groups were comparable in age (prisoners: M = 66.5 years, SD ± 5.3; forensic inpatients: M = 66.8 years, SD ± 7.5) and education (prisoners: M = 11.47, SD ± 2.91; forensic inpatients: M = 11.39, SD ± 3.64), but the offenders in forensic psychiatry had spent significantly more time in the correctional setting than prisoners (prisoners: M = 8.6, SD ± 10.8; forensic inpatients: M = 15.6 years, SD ± 11.9). In both groups cognitive deficits were frequent. Depending on the tests and population, between 42% and 64% showed impairments in global cognition, and between 22% and 70% were classified with impaired executive functioning. We found no significant differences in global cognition or executive functions assessed with the TMT between the two groups. However, forensic inpatients were significantly more impaired in the FAB compared to the prisoners. The results emphasize the high frequency of cognitive dysfunction in both settings and a possibly higher frequency of "frontal" dysfunction in forensic inpatients, and, thus, indicate the relevance of routine neuropsychological diagnostic and treatment procedures in these settings.


Burden of illness in multiple sclerosis (DEFENSE) study: the costs and quality-of-life of Finnish patients with multiple sclerosis.
Although multiple sclerosis (MS) is one of the most common causes of non-traumatic disability among young adults, no published data on its economic and health-related quality-of-life (HRQoL) burden is available from Finland. The DEFENSE study aimed to estimate the costs and HRQoL of patients with MS (PwMS) in Finland and explore how these variables are influenced by disease severity and relapses. Overall, 553 PwMS registered with the Finnish Neuro Society, a national patient association in Finland, completed a self-administered questionnaire capturing information on demographics, disease characteristics and severity (Expanded Disease Severity Scale [EDSS]), relapses, resource consumption and HRQoL. The PwMS had a mean EDSS score of 4.0. Overall, 44.1% had relapsing-remitting form of the disease (RRMS). The mean age was 53.8 years and 55.7% had retired prematurely due to MS. Disease-modifying therapies (DMTs) were used by 42.7% of the study population, and 21.5% across all disease types and severities had experienced relapses during the previous year. The mean total annual cost of MS was €46,994, which increased with advancing disease from €10,835 (EDSS score = 0) to €109,901 (EDSS score = 8-9). The mean utility was 0.644. HRQoL decreased with increasing disease severity. Relapses imposed an additional utility decrement among the PwMS with RRMS and EDSS ≤5 and had a trend-like effect on total costs. The cross-sectional setting did not allow assessment of the significance of relapses in early MS or the use of DMTs on the prognosis of the disease. The study confirms previous findings from other countries regarding a significant disease burden associated with MS and provides, for the first time, published numerical estimates from Finland. Treatments that slow disease progression and help PwMS retain employment for a longer duration have the highest potential to reduce the disease burden associated with MS.


Design of flyback echo-planar readout gradients for magnetic resonance spectroscopic imaging.
The spatial resolution of conventional magnetic resonance spectroscopic imaging-(MRSI) is typically coarse, mainly due to SNR limitations. The increased signal available with higher field scanners and new array coils now permits higher spatial resolution, but conventional chemical shift imaging (phase encoding) limits the spatial coverage possible in a patient-acceptable acquisition time. The "flyback" echo-planar trajectory is particularly insensitive to errors and provides data that are simple to process. In this study, high-efficiency gradient waveforms for flyback echo-planar MRSI were designed and implemented. Normal volunteer studies at 3 T showed the feasibility of acquiring high spatial resolution with large coverage in a short scan time (2048 voxels in 2.3 min and 4096 voxels in 8.5 min). The trajectories were insensitive to errors in timing and require only a modest (10 to 30%) penalty in SNR relative to conventional phase encoding using the same acquisition time.


A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms.
The histological similarities and the common localization are the main causes of difficulties concerning the differential diagnosis between giant cell tumor of bone and chondroblastoma. The purpose of the present study was to detect whether histochemistry and/or immunohistochemistry could help to make the distinction between these two entities easier. The study was based on cases of chondroblastoma and giant cell tumor of bone from patients in the 2nd and 3rd decades of life. Histochemical detection of special intracellular and extracellular components (glycogen, glycosaminoglycans) as well as immunohistochemical investigation using various tumor markers (S-100, NSE, a-1-ACT, lysozyme, fibronectin) were performed on parallel paraffin sections. The presence of abundant intracytoplasmic glycogen granules and the immunoreactivity of the cells of chondroblastoma with S-100 and NSE, together with the presence of acidic sulfated glycosaminoglycans in the stroma, could help the differential diagnosis of this tumor from giant cell tumor of bone.


Evolution of peptides that modulate the spectral qualities of bound, small-molecule fluorophores.
Fluorophore dyes are used extensively in biomedical research to sensitively assay cellular constituents and physiology. We have created, as proof of principle, fluorophore dye binding peptides that could have applications in fluorescent dye-based approaches in vitro and in vivo. A panel of Texas red, Rhodamine red, Oregon green 514 and fluorescein binding peptides, termed here 'fluorettes', was selected via biopanning of a combinatorial library of 12-mer peptides fused to a minor coat pIII protein of the filamentous bacteriophage M13. The 'best' fluorette sequences from each of the groups were subjected to further mutagenesis, followed by a second biopanning to select a new generation of improved fluorettes. Phage were selected that had higher avidity for each fluorophore except Rhodamine red. Of these, peptides were characterized that could specifically and with high affinity bind at least one dye, Texas red, in solution. In addition, the binding of certain peptides to Texas red shifted the peak excitation and/or the emission spectra of the bound dye. Peptides in the context of phage display could readily be selected that could bind to small-molecule fluorophores. The affinities of selected mutant fluorettes could be increased by mutation and further selection. Only a subset of the free peptides could bind free dyes in solution, suggesting that phage context contributed to the selection and ability of certain peptidic regions to independently bind the dyes. Future screens might lead to the creation of other dye-binding peptides with novel characteristics or Texas red derivatives with cross-linking substituents might be designed to increase the utility of the system.


Encapsulated transition metal catalysts comprising peripheral Zn(II)salen building blocks: template-controlled reactivity and selectivity in hydroformylation catalysis.
Encapsulated phosphane ligands can be easily constructed through coordinative interactions between Zn(II)-salphen complexes and pyridylphosphane templates; the template has a pronounced impact on the catalyst structure and consequently on the performance in the hydroformylation of 1-octene.


Prenatally diagnosed hypoplastic left heart syndrome with intact atrial septum and ventriculocoronary arterial fistula.
Intact atrial septum (IAS) and left ventriculocoronary arterial fistula (LVCAF) are the significant risk factors of hypoplastic left heart syndrome (HLHS), and when they are present, prognosis is grim. We report a case of prenatally diagnosed HLHS with IAS and LVCAF that was treated with surgical atrial-septostomy and bilateral pulmonary arterial banding (BPAB) immediately after birth. The Doppler flow pattern of left anterior descending coronary artery (LAD) with dominant retrograde flow was normalized after atrial-septostomy with decompression of left atrial (LA) hypertension. This is the first report showing the influence of atrial-septostomy on coronary flow in HLHS patient with LVCAF.


Effect of cholestyramine and colestipol on the absorption of phenytoin.
The hypocholesterolemic cation resins, cholestyramine and colestipol, have variable effects on the absorption parameters of a number of lipophillic, anion drugs. Because of the unpredictable nature of this interaction, we have assessed in human volunteers the effect of these resins on the rate and total absorption of phenytoin. Our results indicate that these resins do not affect the absorption parameters of phenytoin and that special care does not have to be exercised when these agents are co-administered.


Traumatic hip dislocation in a 21-month-old child.
Traumatic hip dislocation in the paediatric population is a relatively rare occurrence and constitutes an orthopaedic emergency. A trivial force is all that is required and non-accidental injury should not be necessarily suspected. A case report involving a hip dislocation in a 21-month-old child, the youngest in the recent English literature is detailed.


Karyology and tumorigenicity of a simian virus 40-transformed Chinese hamster cell clone.
A pseudodiploid clone of chinese hamster cells tranformed in vitro with Simian virus 40 (SV40) was isolated from soft agar and injected into nude mice through three successive passages with a short in vitro cultivation between each animal inoculation. the original clone and the three subsequent tumor populations were characterized in regard to SV40 T antigen staining, modal chromosome number, and Giemsa-banded karyotype. All tumor cell lines maintained the pseudodiploid mode, as well as the positive sv40 t antigen staining. Nonrandom chromosomal changes included loss of one of the X chromosomes, additions of abnormal variants of chromosomes No. 1 and No. 2, the appearance of unidentified marker chromosomes, and the loss of autosomes No. 5, No. 6, and No. 11. The deletion of one of the X chromosomes occurred with about the same frequency in all cell lines. Additions of abnormal chromosomes No. 1 and No. 2 tended to recur more often in the tumor cell lines than in the original clone. the appearance of marker chromosomes, as well as the loss of autosomes No. 5, No. 6, and No. 11 demonstrated a correlation with tumorigenicity. Yet, the three successive passages of the cells through the animal did not select for a tumor population with a single, homogeneous karyotype.


Brain MRI disease burden and sex differences in cognitive performance of patients with multiple sclerosis.
Although there is evidence that shows worse cognitive functioning in male patients with multiple sclerosis (MS), the role of brain pathology in this context is under-investigated. To investigate sex differences in cognitive performance of MS patients, in the context of brain pathology and disease burden. Brain MRI, neurological examination, neuropsychological assessment (Brief International Cognitive Assessment in MS-BICAMS, and Paced Auditory Verbal Learning Test-PASAT), and patient-reported outcome questionnaires were performed/administered in 1052 MS patients. Females had higher raw scores in the Symbol Digit Modalities Test (SDMT) (57.0 vs. 54.0; p < 0.001) and Categorical Verbal Learning Test (CVLT) (63.0 vs. 57.0; p < 0.001), but paradoxically, females evaluated their cognitive performance by MS Neuropsychological Questionnaire as being worse (16.6 vs 14.5, p = 0.004). Females had a trend for a weaker negative correlation between T2 lesion volume and SDMT ([Formula: see text] = - 0.37 in females vs. - 0.46 in men; interaction p = 0.038). On the other hand, women had a trend for a stronger correlation between Brain Parenchymal Fraction (BPF) and a visual memory test (Spearman's [Formula: see text] = 0.31 vs. 0.21; interaction p = 0.016). All these trends were not significant after correction for false discovery rate. Although, females consider their cognition as worse, males had at a group level slightly worse verbal memory and information processing speed. However, the sex differences in cognitive performance were smaller than the variability of scores within the same sex group. Brain MRI measures did not explain the sex differences in cognitive performance among MS patients.


Risk factors for squamous cell carcinoma of the skin in Saskatchewan, Canada.
Completed questionnaires regarding suspected risk factors for skin cancer were completed by 178 cases of SCC of the skin in Saskatchewan, Canada, and 284 age- sex- and location-matched controls. Significant risk factors identified using chi2 analyses were: farming, family history of skin cancer, light eye color, blond or red hair color, skin types I or II, obvious freckles in childhood, history of severe sunburn, and the use of the herbicide 2,4-Dichlorophenoxy acetic acid. The following relative risks were identified: (1) All cases of SCC of the skin and matched controls: agricultural occupation 1.49, history of severe sunburn 1.49. (2) All men with SCC of the skin and matched controls: history of severe sunburn 1.36 (3) All women with SCC of the skin and matched controls: agricultural occupation 1.83, and skin types I or II 1.48. No association was noted on our study between a history of psoriasis and development of SCC. Neither was an association between smoking and SCC found.


The Nearctic genera of Agathidinae (Hymenoptera: Braconidae) with a phylogenetic analysis, illustrated generic key, and the description of three new genera.
The genera of Nearctic Agathidinae are revised based on a phylogenetic analysis of COI and 28S sequence data; 151 ingroup taxa are included. Three new genera are proposed, i.e., Aphelagathis Sharkey n. gen., Pneumagathis Sharkey n. gen. and Gelastagathis Sharkey n. gen.. The enigmatic species Agathis verticalis Cresson is identified and placed in Aphelagathis, Aphelagathis verticalis (Cresson) n. comb., and a neotype for the species is designated. Two species are described, i.e., Gelastagathis grisselli Sharkey n. sp. and G. frosti Sharkey n. sp. Two new combinations are proposed, Bassus spiracularis Muesebeck and Bassus brooksi Sharkey are transferred to Pneumagathis, Pneumagathis spiracularis (Muesebeck) n. comb., Pneumagathis brooksi (Sharkey) n. comb. An illustrated key to the Nearctic genera of Agathidinae is provided.


Electrophoresis of proteins and DNA on horizontal sodium dodecyl sulfate polyacrylamide gels.
An inexpensive Plexiglas apparatus which allows a simple and rapid preparation of horizontal polyacrylamide gels of different dimensions for different purposes, is described. Preparation of such gels is as easy and rapid as agarose gel preparation, and polymerized polyacrylamide gels are used to fractionate proteins or small DNA fragments using a common horizontal electrophoretic tank. This apparatus was used to electrophoretically fractionate proteins or DNA for immuno-blot analyses, particularly in the study of the allergenic response to Parietaria judaica pollen in senescence, for Southern-blot hybridizations and in the study of DNA polymorphisms.


A comparison of intense pulsed light, combination radiofrequency and intense pulsed light, and blue light in photodynamic therapy for acne vulgaris.
Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) is an emerging modality for the treatment of acne vulgaris. However, optimal therapeutic protocols have not been established. To compare the efficacies of 3 different light sources for activating ALA-induced protoporphyrin IX for the treatment of acne vulgaris. Twenty-two patients with moderate to severe acne vulgaris were randomly assigned to receive ALA-PDT with photoactivation by intense pulsed light (IPL, 600-850 nm), a combination of IPL (580-980 nm) and bipolar radiofrequency (RF) energies, or blue light (417 nm). Each patient received 3 ALA-PDT sessions at 2-week intervals. Follow-up evaluations were conducted 1 and 3 months after the final treatment. At 1 month and 3 months, median lesion count reduction percentages were highest with IPL activation and lowest with blue light activation, although the differences did not reach statistical significance. At 1 month and 3 months, median investigator-assessed improvements were highest with IPL activation and lowest with blue light activation. The variability of responses was significantly smaller with IPL activation than with either RF-IPL or blue light activation. ALA-PDT with activation by IPL appears to provide greater, longer-lasting, and more consistent improvement than either RF-IPL or blue light activation in the treatment of moderate to severe acne vulgaris.


Molecular cloning.
Transcription factor c-Jun is a member of AP-1 transcription complex that can be induced by various pathogens and plays a broad regulatory role in vertebrate immune response. In this study, the complete c-Jun cDNA of large yellow croaker Larimichthys crocea (Lcc-Jun) was cloned, whose open reading frame (ORF) is 984 bp long and encodes a protein of 327 amino acids (aa). The deduced Lcc-Jun protein contains three highly conserved domains, a transactivation domain (TAD, Met1-His118), a DNA binding domain (DBD, Lys218-Arg243), and a Leucine zipper domain (LZD, Leu271-Leu299), as found in other specie c-Jun. Lcc-Jun was constitutively expressed in all examined tissues, with the higher levels in blood, heart, and head kidney. Its transcripts were not only induced in spleen and head kidney by poly (I: C) or LPS, but also up-regulated in primary head kidney leukocytes (PKL), macrophages (PKM), and granulocytes (PKG), suggesting that Lcc-Jun may be involved in immune responses induced by poly (I: C), a viral mimic, and LPS, a Gram-negative bacterial component. Overexpression of Lcc-Jun in PKL increased the expression of cytokines and transcription factors involved in T helper 1 (Th1: TNF-α, IFN-γ, and T-bet) and Th2 (IL-4/13 A/B, IL-6, and GATA3) cell development and differentiation, suggesting that Lcc-Jun may play a role in regulation of Th1/Th2 cell response. These results therefore led us to suggest that the c-Jun-mediated signaling pathways may have an important immune-modulatory function in teleost fish.


Primary hyperparathyroidism is associated with a higher level of serum uric acid: A systematic review and meta-analysis.
Studies have suggested that primary hyperparathyroidism could be a risk factor for hyperuricemia although the results were not consistent across the studies. This systematic review and meta-analysis was performed in order to identify all available studies and summarize their results together. A systematic review was performed using EMBASE and MEDLINE from inception to August 2018 to identify all cohort studies that consisted of 2 cohorts, a cohort of patients with primary hyperparathyroidism and a cohort of individuals without hyperparathyroidism. Eligible studies had to provide data on mean serum uric acid level and standard deviation of both cohorts, which would be extracted to calculate mean difference (MD). Pooled MD was then calculated by combining MDs of each study using a random-effects model. Funnel plot was used for evaluation for publication bias. A total of 9 cohort studies met the inclusion criteria and were included into the meta-analysis. The pooled analysis found that patients with primary hyperparathyroidism had a significantly higher level of serum uric acid than individuals without hyperparathyroidism with the pooled MD of 65.00 μmol/L (95% CI 37.74-92.25). The statistical heterogeneity was high with I2 of 90%. The funnel plot was relatively symmetric and did not provide evidence for publication bias. Patients with primary hyperparathyroidism had a significantly higher level of serum uric acid compared to individuals without hyperparathyroidism.


Cell-mediated immune reaction against BK virus-transformed cells.
Syngeneic or allogeneic cells transformed by BK virus (BKV) were used to immunize C57BL/6J mice. After in vitro stimulation, lymphocytes prepared from the spleens of immunized mice were used in in vitro cytotoxicity tests. The results of these tests revealed the presence of a cell surface antigen, presumably corresponding to the viral transplantation antigen, common to all tested BKV- and SV40-transformed cell lines of C57BL/6J origin. An allogeneic cell line transformed by BKV also contained the same antigen. Immunization, i.e., in vivo priming, did not require syngeneic transformed cells, whereas cytolysis was only observed when the virus-specific antigen on target cells was associated with the same H2 haplotype as was expressed by effector cells. An additional unidentified antigen was shared by some of the BKV-transformed cell lines and cell lines transformed by simian adenovirus SA7.


Quantitative real-time PCR for detection of the neurotoxin gene of Clostridium botulinum type B in equine and bovine samples.
Clostridium botulinum type B is estimated to cause more than 85% of cases of equine botulism in the United States, as well as many outbreaks in cattle. In this study, a quantitative real-time polymerase chain reaction for detection of the neurotoxin gene of C. botulinum type B was compared to the mouse bioassay using 45 positive and 43 negative samples of equine, bovine or associated environmental origin. The sensitivity of the qPCR assay was 96%, whereas the sensitivity of the mouse bioassay was 84%. The specificity of the qPCR assay was 95% and the specificity of the mouse bioassay was 100%.


Single-Cell Sequencing: Current Applications in Precision Onco-Genomics and Cancer Therapeutics.
Single-cell sequencing encompasses a variety of technologies that evaluate cells at the genomic, transcriptomic, epigenomic, and proteomic levels. Each of these levels can be split into additional techniques that enable specific and optimized sequencing for a specialized purpose. At the transcriptomic level, single-cell sequencing has been used to understand immune-malignant cell networks, as well as differences between primary versus metastatic tumors. At the genomic and epigenomic levels, single-cell sequencing technology has been used to study genetic mutations involved in tumor evolution or the reprogramming of regulatory elements present in metastasized disease, respectively. Lastly, at the proteomic level, single-cell sequencing has been used to identify biomarkers important for predicting patient prognosis, as well as biomarkers essential for evaluating optimal treatment strategies. Integrated databases and atlases, as a result of large sequencing experiments, provide a vast array of information that can be applied to various studies and accessed by researchers to further answer scientific questions. This review summarizes recent, high-impact literature covering these aspects, as well as single-cell sequencing in the translational setting. Specifically, we review the potential that single-cell sequencing has in the clinic and its implementation in current clinical studies.


GluNs Detection and Functions in Microglial Cells.
Proving endogenous GluN presence and functions in microglia require complementary steps to demonstrate (1) that GluN genes are transcripted and translated, (2) their cellular localization, (3) that the GluN are functional, and (4) the role of the functional GluN. The complete demonstration is performed by using mRNA detection technics, western blots, immunofluorescence, electrophysiology, calcium imaging, morphology studies, multiplex immunoassay together with conditional microglial Knock-Out mice and brain lesion models.


Mechanical properties and hydroxyproline content of connective tissue in porous ceramic implants.
The present study describes a model applying ceramic implants (A1203) for in vivo studies of connective tissue regeneration. Two types of implants have been developed: a one-piece model for histological examination and chemical analyses, and a two-piece implant which can also be used for mechanical testing of connective tissue. When these were implanted subcutaneoulsly on the back of rats, a correlation was found between the mechanical strength and the hydroxyproline content of connective tissue in the implants. The peak synthesis occurred between the 7th and the 14th day after implantation, and a plateau was reached for both strength-increases and hydroxyproline-formation between the 14th and the 21st days. For histological examination, the implants were embedded in plastic materials and prepared as hard tissue specimens. The model presented can be applied to study connective tissue regeneration in normal and pathological conditions, including studies of the effects of various drugs on the connective tissue.


Comparisons of liver chromatin proteins and template activities in parental and heterotic rats during postweaned development.
Electrophoretic profiles of acid-extractable proteins from Holtzman rat liver chromatin display four minor and five major histone bands through certain stages of postweaned development but are qualitatively different from the chromatin protein profiles previously reported during postweaned development for the Fisher 344 rat strain and the F344 X Holtzman heterotic progeny [Tallman, G., et al. (1979). Biochem, Genet. 17:185]. The protein profiles from the heterotic progeny do not reflect and are not combinations of the profiles from the parental strains. Levels of in vitro transcription with Escherichia coli RNA polymerase of total chromatin and of acid-extracted chromatin from Holtzman rat liver tissue fluctuate in an age-specific manner during postweaned development and are higher than previously published levels determined for the Fisher and F344 X H strains during the same developmental period [Tallman, G., et al. (1978). J. Hered. 69:282]. The degrees of stimulation in the transcription assays resulting from the acid treatment vary with the age of the animal but are similar for the maternal Holtzman and hybrid strains. These studies suggest that regulation of heterotic growth may involve dominant, or maternal genetic influences.


[Catamnestic and endocrinological investigations in women with idiopathic edema (author's transl)].
The clinical picture and the course of idiopathic edema is described after evaluating catamnestic questionnaires on 39 patients. It appears that the syndrome often occurs in other female family members, especially in mothers of propositi and that two thirds of patients have also suffered from symptoms of allergy. In contrast to observations of other groups, diabetes mellitus and slight hypoalbuminemia were found only in a few patients. Secondary hyperaldosteronism was almost exclusively observed in patients who had been taking diuretics during the last few days before the measurements were done. The plasma concentrations of 6 other adrenal steroidal hormones were measured in 33 patients. Only in few of them, mostly patients who had taken diuretics, increased level of 11-deoxycorticosterone, 18-OH-11-deoxycorticosterone and corticosterone were observed. Idiopathic edema does not seem to be a disease entity, but some prediposing factor related to the female reproductive system is likely to exist. Results of systematic psychosomatic studies in our patients will be reported later on.


First-in-Human Study of the Novel Transcatheter Mitral Valve Repair System for Mitral Regurgitation.
Transcatheter mitral valve intervention treatment is a promising alternative therapy for patients with severe mitral regurgitation (MR). This is a multicenter, prospective, first-in-human study of transcatheter edge-to-edge repair (TEER) using a novel device for severe MR. Safety and efficacy were assessed immediately after the procedure and at 30-day follow-up. Twenty-three patients (age 70.0 ± 5.2 years) who were at high/prohibitive surgical risk underwent successful procedures without major periprocedural complications. All patients achieved residual MR ≤2+ at discharge, with 73.9% with 1+ residual MR. The left ventricular end-systolic diameter improved from 4.1 cm at baseline to 3.4 cm at 30-day follow-up. New York Heart Association functional class I/II after TEER was achieved in 87% of patients. This study demonstrated that TEER with the device was feasible and safe for the treatment of patients with severe MR. (Dragonfly-M Transcatheter Mitral Valve Repair System Early Feasibility Study; NCT04528576).


Magnetic resonance imaging: present and future applications.
Magnetic resonance (MR) imaging has created considerable excitement in the medical community, largely because of its great potential to diagnose and characterize many different disease processes. However, it is becoming increasingly evident that, because MR imaging is similar to computed tomography (CT) scanning in identifying structural disorders and because it is more costly and difficult to use, this highly useful technique must be judged against CT before it can become an accepted investigative tool. At present MR imaging has demonstrated diagnostic superiority over CT in a limited number of important, mostly neurologic, disorders and is complementary to CT in the diagnosis of certain other disorders. For most of the remaining organ systems its usefulness is not clear, but the lack of ionizing radiation and MR's ability to produce images in any tomographic plane may eventually prove to be advantageous. The potential of MR imaging to display in-vivo spectra, multinuclear images and blood-flow data makes it an exciting investigative technique. At present, however, MR imaging units should be installed only in medical centres equipped with the clinical and basic research facilities that are essential to evaluate the ultimate role of this technique in the care of patients.


Influence of common preanalytical variations on the metabolic profile of serum samples in biobanks.
A blood pre-centrifugation delay of 24 h at room temperature influenced the proton NMR spectroscopic profiles of human serum. A blood pre-centrifugation delay of 24 h at 4°C did not influence the spectroscopic profile as compared with 4 h delays at either room temperature or 4°C. Five or ten serum freeze-thaw cycles also influenced the proton NMR spectroscopic profiles. Certain common in vitro preanalytical variations occurring in biobanks may impact the metabolic profile of human serum.


Structure-activity relationships of flavonoids as natural inhibitors against E. coli β-glucuronidase.
Bacterial β-glucuronidases play key roles in the deconjugation of a variety of endogenous and drug glucuronides, thus have been recognized as important targets to modulate the enterohepatic circulation of various glucuronides. In this study, more than 30 natural flavonoids were collected and their inhibitory effects against E. coli β-glucuronidase (EcGUS) were assayed. The results demonstrated that some flavonoids including scutellarein, luteolin, baicalein, quercetin and scutellarin displayed strong to moderate inhibitory effects against EcGUS, with the IC50 values ranging from 5.76 μM to 29.64 μM, while isoflavones and dihydroflavones displayed weak inhibitory effects against EcGUS. Further investigation on inhibition kinetics revealed that scutellarein and luteolin functioned as potent competitive inhibitors against EcGUS-mediated PNPG hydrolysis, with the Ki values less than 3.0 μM. Molecular docking simulations demonstrated that scutellarein and luteolin could be well-docked into the catalytic site of EcGUS, while the binding areas of these two natural inhibitors on EcGUS were highly overlapped with that of PNPG on EcGUS. Additionally, the structure-inhibition relationships of natural flavonoids against EcGUS are also summarized, which will be very helpful for the medicinal chemists to design and develop more potent flavonoid-type inhibitors against EcGUS.


Peptide aptamer targeting Aβ-PrP-Fyn axis reduces Alzheimer's disease pathologies in 5XFAD transgenic mouse model.
Currently, no effective therapeutics exist for the treatment of incurable neurodegenerative diseases such as Alzheimer's disease (AD). The cellular prion protein (PrPC) acts as a high-affinity receptor for amyloid beta oligomers (AβO), a main neurotoxic species mediating AD pathology. The interaction of AβO with PrPC subsequently activates Fyn tyrosine kinase and neuroinflammation. Herein, we used our previously developed peptide aptamer 8 (PA8) binding to PrPC as a therapeutic to target the AβO-PrP-Fyn axis and prevent its associated pathologies. Our in vitro results indicated that PA8 prevents the binding of AβO with PrPC and reduces AβO-induced neurotoxicity in mouse neuroblastoma N2a cells and primary hippocampal neurons. Next, we performed in vivo experiments using the transgenic 5XFAD mouse model of AD. The 5XFAD mice were treated with PA8 and its scaffold protein thioredoxin A (Trx) at a 14.4 µg/day dosage for 12 weeks by intraventricular infusion through Alzet® osmotic pumps. We observed that treatment with PA8 improves learning and memory functions of 5XFAD mice as compared to Trx-treated 5XFAD mice. We found that PA8 treatment significantly reduces AβO levels and Aβ plaques in the brain tissue of 5XFAD mice. Interestingly, PA8 significantly reduces AβO-PrP interaction and its downstream signaling such as phosphorylation of Fyn kinase, reactive gliosis as well as apoptotic neurodegeneration in the 5XFAD mice compared to Trx-treated 5XFAD mice. Collectively, our results demonstrate that treatment with PA8 targeting the AβO-PrP-Fyn axis is a promising and novel approach to prevent and treat AD.


Morphological abnormalities in buffalo spermatozoa in fresh and frozen semen.
Spermatozoa of eight Murrah buffalo bulls were diluted in citric acid whey, sodabicarbid-glucose-fructose egg-yolk, and skim milk egg-yolk, respectively, at a rate of 1 : 10, and were stored as liquid or frozen. The morphological evaluation of the spermatozoa revealed a marked superiority of the first-named diluent as regards survival and damage rate under liquid and freezing storage.


The histologic and biomechanical response of two commercially available small glenoid anchors for use in labral repairs.
This study examined histologic characteristics and biomechanical performance of 2 commercially available, small glenoid anchors. Adult research dogs (n = 6) were used for histologic analysis. Anchors were inserted into the lateral rim of the glenoid using the manufacturer's protocol. The dogs were humanely euthanatized 8 weeks after anchor implantation, and the glenoids were collected for histologic analysis. Bone socket width data were compared for statistically significant (P < .05) differences. In addition, 4 matched pairs (n = 8) of human cadaveric glenoids were instrumented with 1 BioComposite SutureTak (Arthrex, Naples, FL, USA) and 1 JuggerKnot (Biomet, Warsaw, IN, USA) suture anchor in the anterior-inferior quadrant. Anchor constructs were preloaded to 5 N, cycled from 5 to 25 N for 100 cycles, and then pulled to failure. All JuggerKnot anchor sites were cyst-like cavities with a rim of dense lamellar bone. All BioComposite SutureTak anchor sites contained intact anchors with close approximation of anastomosing trabeculae of lamellar bone. At 8 weeks after implantation, mean socket width of the JuggerKnot anchor sites was 6.3 ± 2.5 mm, which was significantly (P = .013) larger than the mean socket width of 2.7 ± 0.7 mm measured for the BioComposite SutureTak anchor sites. The JuggerKnot anchor demonstrated larger displacements during subfailure cyclic loading (2.9 ± 1.0 mm compared with 1.3 ± 0.4 mm) and load to failure tests (13.7 ± 6.6 mm compared with 3.2 ± 0.5 mm). Statistical differences (P < .01) existed in every category except ultimate load. Based on the biomechanical in human bone and histologic findings in canine subjects, the all-suture anchor may be at risk for clinical failure.


The angiotensin AT2 receptor modulates T-type calcium current in non-differentiated NG108-15 cells.
We report here that angiotensin II (AII) and the AT2 receptor-selective ligand, CGP 42112, modulate the T-type calcium current in non-differentiated NG108-15 cells, which express only AT2 receptors. Both peptides decrease the T-type calcium current at membrane potentials above -40 mV and shift the current-voltage curve at lower potentials with maximal effect between 5 and 10 min after application. These data describe a new cellular response to AII and suggest that the AT2 receptor mediates certain neurophysiological actions of this hormone.


Relationship between plasma renin activity and physical fitness in normal subjects.
The relationship between plasma renin activity (PRA) at rest and physical fitness was studied in 40 normal young subjects on a liberal sodium intake. Plasma renin activity was measured in arterial blood withdrawn at the end of a 30-min period of rest in recumbency, while physical fitness was expressed by the highest oxygen uptake achieved during an uninterrupted graded exercise test performed in the sitting position on an electromagnetically braked ergometer bicycle (peak VO2). Log PRA correlated significantly and inversely with peak VO2 adjusted for body weight (r = -0.34; P less than 0.05) in single regression analysis. Using multiple regression and adjusted peak VO2, age, urinary sodium excretion and mean intra-arterial pressure as independent variables, no combination of two or more independent variables yielded significant partial correlation coefficients with log PRA. This correlation suggests that PRA at rest is inversely related to the subject's physical fitness.


Toward a hemorrhagic trauma severity score: fusing five physiological biomarkers.
To introduce the Hemorrhage Intensive Severity and Survivability (HISS) score, based on the fusion of multi-biomarker data; glucose, lactate, pH, potassium, and oxygen tension, to serve as a patient-specific attribute in hemorrhagic trauma. One hundred instances of Sensible Fictitious Rationalized Patient (SFRP) data were synthetically generated and the HISS score assigned by five clinically active physician experts (100 [5]). The HISS score stratifies the criticality of the trauma patient as; low(0), guarded(1), elevated(2), high(3) and severe(4). Standard classifier algorithms; linear support vector machine (SVM-L), multi-class ensemble bagged decision tree (EBDT), artificial neural network with bayesian regularization (ANN:BR) and possibility rule-based using function approximation (PRBF) were evaluated for their potential to similarly classify and predict a HISS score. SVM-L, EBDT, ANN:BR and PRBF generated score predictions with testing accuracies (majority vote) corresponding to 0.91 ± 0.06, 0.93 ± 0.04, 0.92 ± 0.07, and 0.92 ± 0.03, respectively, with no statistically significant difference (p > 0.05). Targeted accuracies of 0.99 and 0.999 could be achieved with SFRP data size and clinical expert scores of 147[7](0.99) and 154[9](0.999), respectively. The predictions of the data-driven model in conjunction with an adjunct multi-analyte biosensor intended for point-of-care continual monitoring of trauma patients, can aid in patient stratification and triage decision-making.


[Enterostomy and associated problems].
Stoma has been used in colorectal surgery for various indications. Stoma type and stoma location are associated with stoma complications and quality of life with a stoma. The question regarding how to avoid stoma complication and improve quality of life should be considered when stoma creation is planned. The benefit of stoma should be balanced with complications brought about by stoma creation.


Hyperammonemia Alters the Function of AMPA and NMDA Receptors in Hippocampus: Extracellular cGMP Reverses Some of These Alterations.
Chronic hyperammonemia alters membrane expression of AMPA and NMDA receptors subunits in hippocampus leading to impaired memory and learning. Increasing extracellular cGMP normalizes these alterations. However, it has not been studied whether hyperammonemia alters the function of AMPA and NMDA receptors. The aims of this work were: (1) assess if hyperammonemia alters AMPA and NMDA receptors function; (2) analyze if extracellular cGMP reverses these alterations. A multielectrode array device was used to stimulate Schäffer collaterals and record postsynaptic currents in the CA1 region in hippocampal slices from control and hyperammonemic rats and analyze different features of the excitatory postsynaptic potentials. Hyperammonemia reduces the amplitude and delays appearance of AMPA EPSPs, whereas increases amplitude, hyperpolarization, depolarization and desensitization area of the NMDA EPSPs. These alterations in AMPA and NMDA function are accentuated as the stimulation intensity increases. Adding extracellular cGMP reverses the alteration in amplitude in both, AMPA and NMDA EPSPs. In control slices extracellular cGMP decreases the AMPA and NMDA EPSPs amplitude and delays the response of neurons and the return to the resting potential at all stimulation intensities. In conclusion, hyperammonemia decreases the AMPA response, whereas increases the NMDA response and extracellular cGMP reverses these alterations.


Improved design of nasogastric feeding tubes.
Disappointed with the overall performance of weighted and unweighted nasogastric feeding tubes, a design programme was initiated which resulted in the development of two new nasogastric tubes, one weighted and one unweighted. The tubes were manufactured with polyurethane rather than polyvinylchloride (PVC) which permitted an increase in diameter of the internal lumen which in turn was coated with water activated lubricant to ease removal of the introducer wire. A specially modelled outflow port was incorporated into the tips of both tubes. The performance of the two new polyurethane nasogastric feeding tubes was assessed under controlled trial condition using as a reference a widely used PVC unweighted open ended tube. While intubation times were similar in patients without concurrent endotracheal intubation, it took a significantly shorter time to intubate patients with concurrent endotracheal intubation with the new weighted tube. Following tube intubation, it was possible to aspirate gastric contents significantly more often through the new polyurethane tubes (p < 0.001) than through the PVC tube, and the unweighted polyurethane tube stayed in situ longer (p < 0.05) than the PVC tube. The newly designed polyurethane nasogastric feeding tubes are the first tubes that have been shown to have advantages over the simpler type of open ended, unweighted PVC nasogastric feeding tubes.


Evaluation of a web-based self-reporting method for monitoring international passengers returning from an area of emerging infection.
Emerging infectious diseases are a public health issue of international concern. Identifying methods to limit their expansion is essential. We assessed the feasibility of a screening strategy in which each traveler would actively participate in the screening process after an intercontinental flight by reporting their own health status via a web-based self-administered questionnaire. In 2015 and 2017, we invited passengers arriving at or departing from Pointe-à-Pitre international airport to answer an online health questionnaire during the four days following their arrival from or at Paris-Orly international airport. SPIRE 1 was intended for passengers arriving at Pointe-à-Pitre and was conceived as a pilot study. SPIRE 2 was an improved version of SPIRE 1 and consisted in three parts, which permitted to further assess the benefits of pre-flight request and email follow-up. Endpoints were the connection rates and response rates to online health questionnaire. For SPIRE 1, 4/1038 travelers (0.4%) completed the two steps of the online health questionnaire. In SPIRE 2, response rates ranged from 3/1059 (0.3%) to 19/819 (2.3%). Response rates were significantly better when passengers were approached before their flight. The yield of an online health questionnaire was unexpectedly low.


Systematic review of the relationship between comorbidity and out-of-hospital cardiac arrest outcomes.
To assess the current evidence on the effect pre-arrest comorbidity has on survival and neurological outcomes following out-of-hospital cardiac arrest (OHCA). Systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. MEDLINE, Ovid Embase, Scopus, CINAHL, Cochrane Library and MedNar were searched from inception to 31 December 2018. Studies included if they examined the association between prearrest comorbidity and OHCA survival and neurological outcomes in adult or paediatric populations. Data were extracted from individual studies but not pooled due to heterogeneity. Quality of included studies was assessed using the Newcastle-Ottawa Quality Assessment Scale. This review included 29 observational studies. There were high levels of clinical heterogeneity between studies with regards to patient recruitment, inclusion criteria, outcome measures and statistical methods used which ultimately resulted in a high risk of bias. Comorbidities reported across the studies were diverse, with some studies reporting individual comorbidities while others reported comorbidity burden using tools like the Charlson Comorbidity Index. Generally, prearrest comorbidity was associated with both reduced survival and poorer neurological outcomes following OHCA with 79% (74/94) of all reported adjusted results across 23 studies showing effect estimates suggesting lower survival with 42% (40/94) of these being statistically significant. OHCA survival was particularly reduced in patients with a prior history of diabetes (four out of six studies). However, a prearrest history of myocardial infarction appeared to be associated with increased survival in one of four studies. Prearrest comorbidity is generally associated with unfavourable OHCA outcomes, however differences between individual studies makes comparisons difficult. Due to the clinical and statistical heterogeneity across the studies, no meta-analysis was conducted. Future studies should follow a more standardised approach to investigating the impact of comorbidity on OHCA outcomes. CRD42018087578.


A survey on surgeons' attitudes and practices in the care of HIV-infected patients in Japan.
We conducted a survey to learn surgeons' attitudes and practices concerning HIV-infected patients in Japan. We mailed questionnaires to 174 general hospitals and received responses from 126 (72.6%). Concerning preoperative HIV testing, 41% of the hospitals had never performed it. Twenty-nine percent had operated on at least one HIV-infected patient and 144 HIV-infected patients have received surgery under spinal, epidural or general anesthesia. During surgery, 6 accidental needlesticks occurred, but fortunately no seroconversion has been reported since the accidents. Therefore widerspread use of barrier precautions should be undertaken during surgical intervention. This survey revealed that 40-60% of the hospitals coped inadequately with such surgery. Therefore it is important to arrange a system in Japan so that HIV-infected patients will be able to receive necessary surgical treatment. For that purpose, a medical educational program for health care professionals is needed, because not only surgeons but all health care professionals in hospitals should be able to take part in the treatment of HIV-infected patients.


Cross-sectional study examining whether the extent of first-contact access to primary care differentially benefits those with certain personalities to receive preventive services.
The extent of first-contact access to primary care (ie, easy availability when needed) is associated with receiving recommended preventive services. Whether this access benefits patients at risk of preventive services underutilisation, such as those with certain personality characteristics, is unclear. Secondary analysis of the 2003-2006 round of the Wisconsin Longitudinal Study. 6975 respondents who reported a usual provider whose specialty was internal medicine or family medicine. Those reporting not visiting a medical provider in the past 12 months, and those who were uninsured were excluded. Receiving mammography, cholesterol testing and influenza vaccination. Adjusted predicted probabilities (aPP) of receiving these services were analysed stratified by personality characteristics overall, and if significant, then interacted with first-contact access. Lower conscientiousness as compared with higher conscientiousness predicted less of all 3 preventive services; mammography (aPP 80%; 95% CI (77% to 83%) vs aPP 85%; (95% CI 82% to 87%)), cholesterol testing (88%; (85% to 90%) vs 93% (91% to 94%), and influenza vaccination (62%; (59% to 64%) vs 66%; (63% to 68%)). Lower agreeableness as compared with higher agreeableness predicted less mammography (77%; (73% to 81%) vs 84%; (82% to 87%)) and less influenza vaccination (59%; (56% to 62%) vs 65%; (63% to 68%)). Lower extraversion predicted less cholesterol testing (88%; (86% to 91%) vs (92%; (90% to 94%)). Lower openness to experience predicted less influenza vaccination (59%; (56% to 63%) vs (68%; (65% to 70%)). For agreeableness, these differences in receiving preventive services did not persist when first-contact access to primary care was present. Certain personality characteristics predicted receiving less preventive care services. For those with less agreeableness, improved first-contact access to primary care mitigated this effect. If these results are replicated in other studies, primary care offices seeking to improve population health through receiving preventive services should prioritise increasing their first-contact accessibility.


Controlling the Polymorphism and Topology Transformation in Porphyrinic Zirconium Metal-Organic Frameworks via Mechanochemistry.
Tetratopic porphyrin-based metal-organic frameworks (MOFs) represent a particularly interesting subclass of zirconium MOFs due to the occurrence of several divergent topologies. Control over the target topology is a demanding task, and reports often show products containing phase contamination. We demonstrate how mechanochemistry can be exploited for controlling the polymorphism in 12-coordinated porphyrinic zirconium MOFs, obtaining pure hexagonal PCN-223 and cubic MOF-525 phases in 20-60 min of milling. The reactions are mainly governed by the milling additives and the zirconium precursor. In situ monitoring by synchrotron powder X-ray diffraction revealed that specific reaction conditions resulted in the formation of MOF-525 as an intermediate, which rapidly converted to PCN-223 upon milling. Electron spin resonance measurements revealed significant differences between the spectra of paramagnetic centers in two polymorphs, showing a potential of polymorphic Zr-MOFs as tunable supports in spintronics applications.


Radiolabeled liposomes and lipoproteins as lipidic nanoparticles for imaging and therapy.
Radiolabeled lipidic nanoparticles, particularly liposomes and lipoproteins, are of great interest as agents for imaging and therapy, due not only to their peculiar physicochemical and biological properties, but also to their great versatility and the ability to manipulate them to obtain the desired properties. This review provides an overview of radionuclide labeling strategies for preparing diagnostic and therapeutic nanoparticles based on liposomes and lipoproteins that have been developed to date, as well as the main quality control methods and in vivo applications.