Comparative study on sample stacking by moving reaction boundary formed with weak acid and weak or strong alkali in capillary electrophoresis: I. Theory.
The condensation of low abundance zwitterion substance, such as protein and peptide, has great significance to the study on proteomics. This paper develops the theory on design of online stacking conditions of zwitterion by a moving reaction boundary (MRB) in capillary electrophoresis (CE). This concerns the choice of running and sample buffers, velocity design of MRB, and salt effect on the stacking. The theoretical results unveil that: (1) the velocity of MRB formed with weak acidic buffer and strong alkali should be set between zero and the velocity of zwitterion in the alkali phase, or no stacking occurs; (2) if a strong alkali is used to prepare the sample, a much long front plug of strong base must be injected before the alkaline sample plug for complete stacking, whereas no such front plug is needed if a weak alkali with enough high concentration and pH value is used to prepare the sample buffer; (3) the existence of salt in sample matrix has a weak effect on the stacking of zwitterion if sample is prepared with weak alkaline buffer, while has a dramatic effect on the same stacking if with a strong base buffer. In addition, the concentration of weak alkali used for preparation of sample should be set at the point, at which the velocity of MRB is as much as possible close to that of negative zwitterion. The developed theory and its computation are quantitatively proved by the experiments of zwitterion stacking by the MRB as shown in the previous and the accompanying papers. The proposed theoretic results hold obvious significances on-column stacking of low abundance zwitterions, such as amino acid, or peptides or proteins, in CE.


Post-operative hypertension during early recovery following liver tumour ablation: A retrospective study.
High-frequency jet ventilation is necessary to reduce organ movements during stereotactic liver ablation. However, post-operative hypertensive episodes especially following irreversible electroporation ablation compared with microwave ablation initiated this study. The hypothesis was that hypertensive episodes could be related to ventilation or ablation method. The aim of this retrospective study was to assess the proportion of patients with hypertensive events during recovery following liver ablation under general anaesthesia and to analyse the relation to ventilation and ablation technique. A medical chart review of 134 patients undergoing either high-frequency jet ventilation and microwave ablation (n = 45), high-frequency jet ventilation and irreversible electroporation (n = 44), or conventional ventilation and microwave ablation (n = 45) was performed. The proportion of patients with at least one episode of systolic arterial pressure 140-160, 160-180 or >180 mmHg during early recovery and the impact of ventilation method was studied. Out of 134 patients, 100, 75 and 34 patients had at least one episode of mild, moderate and severe hypertension. Microwave ablation, as well as high frequency jet ventilation, was associated with an increased odds ratio for post-operative hypertension. The proportion of patients with at least one severe hypertensive event was 18/45, 9/44 and 7/45, respectively. Both ventilation and ablation technique had an impact on post-operative hypertensive episodes. The microwave ablation/high-frequency jet ventilation combination increased the risk as compared with irreversible electroporation/high-frequency jet ventilation and microwave ablation/conventional ventilation.


V.PhyloMaker2: An updated and enlarged R package that can generate very large phylogenies for vascular plants.
An earlier version of V.PhyloMaker has been broadly used to generate phylogenetic trees of vascular plants for botanical, biogeographical and ecological studies. Here, we update and enlarge this package, which is now called 'V.PhyloMaker2'. With V.PhyloMaker2, one can generate a phylogenetic tree for vascular plants based on one of three different botanical nomenclature systems. V.PhyloMaker2 can generate phylogenies for very large species lists (the largest species list that we tested included 365,198 species). V.PhyloMaker2 generates phylogenies at a fast speed. We provide an example (including a sample species list and an R script to run it) in this paper to show how to use V.PhyloMaker2 to generate phylogenetic trees.


Genomic Analysis of Soybean PP2A-B ' ' Family and Its Effects on Drought and Salt Tolerance.
Abiotic stresses induce the accumulation of reactive oxygen species (ROS) and significantly affect plant growth. Protein phosphatase 2A (PP2A) plays an important role in controlling intracellular and extracellular ROS signals. However, the interaction between PP2A, ROS, and stress tolerance remains largely unclear. In this study, we found that the B ' ' subunit of PP2A (PP2A-B ' ' ) can be significantly induced and was analyzed using drought- and salt-induced soybean transcriptome data. Eighty-three soybean PP2A-B ' ' genes were identified from the soybean genome via homologous sequence alignment, which was distributed across 20 soybean chromosomes. Among soybean PP2A-B ' ' family genes, 26 GmPP2A-B ' ' members were found to be responsive to drought and salt stresses in soybean transcriptome data. Quantitative PCR (qPCR) analysis demonstrated that GmPP2A-B ' ' 71 had the highest expression levels under salt and drought stresses. Functional analysis demonstrated that overexpression of GmPP2A-B ' ' 71 in soybeans can improve plant tolerance to drought and salt stresses; however, the interference of GmPP2A-B ' ' 71 in soybean increased the sensibility to drought and salt stresses. Further analysis demonstrated that overexpression of GmPP2A-B ' ' 71 in soybean could enhance the expression levels of stress-responsive genes, particularly genes associated with ROS elimination. These results indicate that PP2A-B ' ' can promote plant stress tolerance by regulating the ROS signaling, which will contribute to improving the drought resistance of crops.


Kaempferol Induces Cell Death and Sensitizes Human Head and Neck Squamous Cell Carcinoma Cell Lines to Cisplatin.
Cisplatin is a first-line chemotherapeutic drug commonly used to treat patients with head and neck cancer; nevertheless, cisplatin resistance poses a main challenge for its clinical efficacy. Recent studies have shown that kaempferol, a natural flavonoid found in various plants and foods, has an anticancer effect. The following study evaluated the cytotoxic effects of kaempferol on head and neck tumor cells and their mechanism of action, evaluating the effects on proliferation, the oxygen consumption rate, transmembrane potential, tumor cell migration and induction of apoptosis. Moreover, we determined the effects of a combination of kaempferol and cisplatin on head and neck tumor cells. We found that kaempferol inhibited the oxygen consumption rate and decreased the intracellular ATP content in tumor cells. This novel mechanism may inhibit the migratory capacity and promote antiproliferative effects and apoptosis of tumor cells. Additionally, our in vitro data indicated that kaempferol may sensitize head and neck tumor cells to the effects of cisplatin. These effects provide new evidence for the use of a combination of kaempferol and cisplatin in vivo and their future applications in head and neck cancer therapy.


The Italian Registry for Adrenal Cortical Carcinoma: analysis of a multiinstitutional series of 129 patients. The ACC Italian Registry Study Group.
Adrenal cortical carcinoma is an uncommon tumor with a poor prognosis. The low incidence of this tumor makes it difficult to achieve reliable data on clinical manifestations, natural history, and the impact of therapies. The purpose of this study was to evaluate such aspects in a large series. A retrospective series of 129 cases (55 men and 74 women, mean age of 49 years) was collected from 18 surgical institutions. At the time of diagnosis 45.7% of patients had endocrine symptoms. One hundred twenty-four patients underwent surgery, which was considered curative in 91 cases and palliative in 33. Sixty-three patients had local disease, 48 had regional disease, and 43 had distant metastases. This study confirmed a higher incidence in the 40- to 50-year-old population with a female prevalence; hormonal hyperincretion was more common in women, but it was not caused by advanced disease. The overall 5-year survival rate was 35%. Tumor stage and curative resection affected prognosis significantly. The influence of gender, side, age, and hormonal function has not been confirmed. Adjuvant therapies were ineffective in prolonging survival. Reoperated patients experienced better survival (mean, 41.5 months) than nonreoperated cases (mean, 15.6 months). The poor prognosis of adrenal cortical carcinoma may be improved by early diagnosis and complete resection. Radical surgery is the sole effective therapy, particularly in early stages. Surgical treatment of recurrence seems to improve survival and should be attempted systematically. Adjuvant therapies obtained contrasting results, and their role should be evaluated in prospective multicentric trials.


Palliative medicine referral in patients undergoing continuous renal replacement therapy for acute kidney injury.
Referral patterns for palliative medicine consultation (PMC) by intensivists for patients requiring continuous renal replacement therapy (CRRT) have not been studied. We retrospectively analyzed clinical data on patients who received CRRT in a tertiary referral center between 1999 and 2006 to determine timeliness and effectiveness of PMC referrals and mortality rate as a surrogate for safety among patients receiving CRRT for acute kidney injury. Over one-fifth (21.1%) of the 230 CRRT patients studied were referred for PMC (n = 55). PMC was requested on average after median of 15 hospital and 13 intensive care unit (ICU) days. Multivariate regression analysis revealed no association between mortality risk and PMC. Total hospital length of stay for patients who died after PMC referral was 18.5 (95% CI = 15-25) days compared with 12.5 days (95% CI = 9-17) for patients who died without PMC referral. ICU care for patients who died and received PMC was longer than for patients with no PMC [11.5 (95% CI = 9-15) days vs. 7.0 (95% CI = 6-9) days, p < 0.01]. CRRT duration was longer for patients who died and received PMC referral than for those without PMC [5.5 (95% CI = 4-8) vs. 3.0 (95% CI = 3-4) days; p < 0.01]. PMC was safe, but referrals were delayed and ineffective in optimizing the utilization of intensive care in patients receiving CRRT. A proactive, "triggered" referral process will likely be necessary to improve timeliness of PMC and reduce duration of non-beneficial life-sustaining therapies.


Challenge of mast cells with increasing amounts of antigen induces desensitization.
In vivo rush desensitization is a procedure widely employed to quickly desensitize allergic patients by administering increasing doses of the offending antigen at short intervals. The mechanism(s) underlying this process and the possible role of mast cells in it have not been well delineated. To define an ex vivo model for rush desensitization utilizing the mast cell-fibroblast coculture system. Rat peritoneal mast cells were cultured on 3T3 fibroblasts and were preincubated with saturating or suboptimal concentrations of IgE anti-DNP antibodies. Mast cells were then repeatedly challenged at 30 min intervals, with increasing amounts (0.001-100 ng/mL) of the antigen DNP-HSA, in the presence of calcium ions. Parallel control cultures were stimulated only once by each antigen concentration. In another set of experiments, mast cells were repeatedly activated with increasing concentrations (0.1-1000 ng/mL) of compound 48/80. Supernatants and cell sonicates were assessed for histamine content and the percentage of histamine released was calculated. When saturating concentrations of IgE anti-DNP antibodies were used, mast cells challenged repeatedly with DNP-HSA did not release significant amounts of histamine up to an antigen concentration of 1 ng/mL. At this stage they were partially desensitized, releasing only 108.3 +/- 17.1 ng histamine/plate (7.9 +/- 0.8%). A marked desensitization was observed at optimal antigen concentration (100 ng/mL), where experimental mast cells released only 45.6 +/- 10.9 ng/plate, compared with 661.9 +/- 48.2 ng/plate in firstly challenged cultures. Desensitization was probably not due to mast cells histamine depletion, since the cells still contained large amounts of histamine (579.5 +/- 108.6 ng/plate) at the end of the procedure. A similar pattern of desensitization was observed when mast cells were preincubated with a suboptimal concentration of IgE antibodies. Activation of mast cells with increasing amounts of the IgE-independent secretagogue, compound 48/80, did not cause desensitization since at each concentration both repetitively challenged and control cultures released similar amounts of histamine. Furthermore, challenge of antigen-desensitized mast cells with compound 48/80 caused the release of 75.9 +/- 4.9% histamine comparable to the percentage of histamine released from controls (79.5 +/- 6.7). Repeated exposure of mast cells to gradually increasing amounts of antigen induces their refractoriness. This observation would suggest a role for mast cells in rush desensitization procedure in vivo. Our coculture system may serve as a useful model for studying this process.


Use of a claims-based active drug safety surveillance system to assess the risk of acute pancreatitis with exenatide or sitagliptin compared to metformin or glyburide.
To estimate risk and relative risk (RR) of acute pancreatitis among patients using incretin-based diabetes therapies (exenatide or sitagliptin) compared to patients treated with agents with established safety profiles (metformin or glyburide). The study population was derived from a large US commercial health insurance transaction database using an active drug safety surveillance system (i3 Aperio). This analysis is based on data from June 2005 through June 2008. Cohorts of exenatide and sitagliptin initiators were each matched to an equal number of metformin or glyburide (met/gly) initiators using propensity scores to reduce confounding in the comparison of outcomes during follow-up. Patients with claims suggesting pancreatic disease in the 6 months prior to cohort entry were excluded. Claims for hospitalizations associated with a primary diagnosis of acute pancreatitis (ICD-9 577.0). There were 27 996 exenatide initiators and 16 276 sitagliptin initiators and approximately equal numbers of matched comparators. During follow-up of up to 1 year, acute pancreatitis occurred among 0.13% of patients treated with exenatide and 0.12% of patients treated with sitagliptin. The risk of acute pancreatitis was comparable for initiators of exenatide (RR 1.0; 95% confidence interval (CI) 0.6-1.7) and sitagliptin (RR 1.0; 95% CI 0.5-2.0) relative to the comparison cohorts. These data do not provide evidence for an association of acute pancreatitis among initiators of exenatide or sitagliptin compared to met/gly initiators. These results are limited by the data available in an administrative, healthcare database.


The effects of postmenopausal Vitamin D treatment on vaginal atrophy.
To evaluate the efficacy of Vitamin D for relieving vaginal atrophy. In our cross-sectional study, 60 eligible women were consecutively identified among patients who were followed in physical medicine and rehabilitation's outpatient clinic, during the period March June 2001. The sample consisted of 30 postmenopausal women on 1,25-dihydroxy Vitamin D (calcitriol) treatment, 30 postmenopausal women taking neither hormone replacement nor osteoporosis treatment. Vaginal atrophy was determined by symptoms, physical examination and maturation index (MI). The mean physical findings score in Vitamin D treatment (VDT) group was significantly lower than the mean physical findings score in the group without treatment. Symptom scores were lower in both groups and there was not significantly difference between two groups. As maturation indices: in VDT group, superficial cells proportion was significantly higher and basal, parabasal cells proportion was lower than in the group without treatment. The results of current study seem to indicate that vaginal tissue may be a new target organ for therapeutically applied Vitamin D analogues.


Using a scheduled caesarean birth plan: A cross-sectional exploration of women's perspectives.
There is minimal evidence regarding the role or impact of birth plans from the perspective of women experiencing scheduled caesarean birth. Quality maternity care requires respect for women's preferences. Evidence suggests birth plans enable communication of women's preferences and may enhance agency when vaginal birth is intended, however there is limited evidence of how this translates in the perioperative environment where caesarean birth is the intended outcome. Explore the experiences and perspectives of women who had utilised a scheduled caesarean birth plan at an Australian tertiary maternity hospital. A cross-sectional design was used; 294 participants completed the survey within two weeks post-birth. Descriptive statistics were used to analyse quantitative data, qualitative responses were analysed using content analysis. Over half of the women requested lowering of the surgical-screen at birth, most requested immediate skin-to-skin with their babies; around two-thirds of these preferences were met. Use of a birth plan for scheduled caesarean section supported women's ability to communicate their desires and choices, enhancing agency and reinforcing the significance of the caesarean birth experience. Qualitative data revealed two main categories: Perceptions and experiences; and Recommendations for improvement, with corresponding sub-categories. Findings provide unique opportunities to consider the provision of woman-centred care within the highly technocratic perioperative environment. All women, regardless of birth mode, have a right to respectful maternity care that prioritises their wishes and agency. This study provides evidence for the positive utility of birth plans in caesarean birth, local adaptation is encouraged.


A method comparison study of the high throughput automated HISCL® SARS-CoV-2 antigen assay using nasopharyngeal swab samples from symptomatic and asymptomatic subjects against conventional RT-PCR.
Our study aim was to evaluate the performance of the automated Sysmex HISCL® severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen assay against reverse-transcription polymerase chain reaction (RT-PCR). We tested 277 remnant frozen nasopharyngeal swab samples, stored in universal transport medium (UTM), yielding a sensitivity of 94.9% against historical RT-PCR results with cycle threshold (Ct ) < 30, and a sensitivity of 76.7% for Ct < 35, and specificity of 100% (all Ct values) confirming compatibility of UTM-diluted samples with the assay system. Thereafter, we prospectively collected 141 nasopharyngeal swab samples in UTM from healthcare workers and 1369 paired swabs (400 UTM; 969 dry) from individuals at a public health testing center, with the first swab (UTM) reserved for RT-PCR, yielding a positivity rate of 4.6%. HISCL assay performance using UTM swabs was superior to dry swabs, with a sensitivity of 100% (95% confidence interval [CI] 71.5%-100%) at Ct < 30 versus 92.3% (95%CI 81.5%-97.9%), and a specificity of 99.3% (95% CI 98.1-99.89) against 83.3% (95%CI 80.7%-85.6%). We conclude that this antigen assay is suitable for high throughput facilities where the primary indication for testing is to rule out infection with low RT-PCR Ct values (proxy for high viral loads) to curb viral spread.


On the stratification of human bile and its importance for the solubility of cholesterol.
Stratification (layer formation) is noted in vitro in hepatic bile collected after interruption of the enterohepatic circulation. Hepatic bile is still layered after more than 12 hr when collected in this way (continuously or in fractions) in a bag made of a semipermeable membrane (simulating an atonic gall bladder) and concentrated. Cholesterol solubility is very slight in the upper layer. This phenomenon may be important for precipitation of cholesterol and the formation of gallstones, since the enterohepatic circulation is interrupted when bile is stored and concentrated in the gall bladder. This condition may be prolonged by temporary stasis, which has always been considered one of the main factors in the formation of gallstones.


The effect of stimulus bandwidth on the nonlinear-derived tone-burst-evoked otoacoustic emission.
Intermodulation distortion has been hypothesized as a mechanism contributing to the generation of short-latency (SL) components in the transient-evoked otoacoustic emission (TEOAE). Presumably, nonlinear interactions between the frequency components within the evoking stimulus induce cochlear distortion products, which mix in the cochlea and ear canal with reflected energy from each stimulus-frequency's tonotopic place. The mixing of these different components is evidenced in the bandpass-filtered emission waveform as a series of different latency peaks. The current study tested the hypothesis that intermodulation distortion, induced within the spectral bandwidth of the evoking stimulus, is the primary mechanism through which the SL components are generated. The nonlinear-derived tone-burst-evoked OAE (TBOAEnl) was evoked using 2-kHz tone bursts with durations of 3, 6, 12, and 24 cycles. As tone burst duration doubled, the spectral bandwidth was halved. It was hypothesized that contributions to the TBOAEnl from SL components would decrease as tone burst duration increased and spectral bandwidth decreased, if the SL components were generated through intermodulation distortion. Despite differences in spectral bandwidth between the evoking stimuli, the latencies and magnitudes of the different latency components between the 3- and 6-cycle TBOAEnl were comparable. The 12- and 24-cycle TBOAEnl envelopes were characteristic of destructive phase interactions between different latency components overlapping in time. The different latency components in the 3- and 6-cycle TBOAEnl introduced a characteristic level dependency to TBOAEnl magnitude and latency when analyzed across a broad time window spanning the different components. A similar dependency described the 12- and 24-cycle TBOAEnl input/output and latency-intensity functions, suggesting that the SL components evident in the shorter-duration TBOAEnl equally contributed to the longer-duration TBOAEnl, despite reductions in spectral bandwidth. The similarity between the different TBOAEnl suggests that they share a common generation mechanism and casts doubt on intermodulation distortion as the generation mechanism of SL TEOAE components in humans.


The Kuroshio radiocesium stream.
The Fukushima accident released short-lived Cs-134 and longer-lived Cs-137 to the ocean. The amount, although substantial, is much less than that produced during the atomic bomb tests 60 years ago. But, the latter has received little attention. Here we found only Cs-137 in waters near the origin of the Kuroshio. The speed of the Kuroshio current generally decreases with water depth, yet, the Cs-137 activity increases with depth to reach a subsurface maximum of 2.4 Bq m-3. As a result, a core of high Cs-137 flux, or a radiocesium stream, exists at approximately 200-400 m in depth. In total, the Kuroshio transports about 1 PBq year-1 Cs-137 northward between 121 and 123°E, 1000 times more than the 0.73-1.0 TBq year-1 discharged to the ocean at Fukushima in 2016-2018.


Differential effects of calcium channel antagonists on histamine and pentagastrin-stimulated gastric acid secretion in the rat.
Different calcium channel antagonists have been assessed for their ability to inhibit gastric acid secretion in rats. Whereas verapamil, diltiazem and cinnarizine inhibited pentagastrin-induced gastric acid secretion but not histamine-induced secretion, nifedipine selectively inhibited the stimulant effect of histamine. In contrast, the vasodilator hydralazine had non-selective effects. These findings indicate that calcium-antagonists may have differential effects against different secretagogues and these effects are not simply related to hypotensive effects.


Frequency Rhythmic Electrical Modulation System (FREMS) to alleviate painful diabetic peripheral neuropathy: A pilot, randomised controlled trial (The FREMSTOP study).
Frequency Rhythmic Electrical Modulated System (FREMS) is a non-invasive treatment for chronic pain conditions, but its place in the treatment algorithm for painful diabetic peripheral neuropathy (PDPN) is unknown. A pilot, open-label, randomised controlled trial in individuals with PDPN inadequately controlled on at least dual neuropathic pain treatments recruited from primary and secondary care. Participants were randomised 1:1 to FREMS + usual care (n = 13) versus usual care (n = 12). Primary outcome was change from baseline in perceived pain (assessed by visual analogue scale) at 12 weeks between treatment groups. Of 25 participants, 14 (56%) were men, and 21 (84%) were White Europeans. Median (IQR) age and duration of diabetes were 64 (56, 68) and 14 (10, 20) years, respectively. At 12 weeks, FREMS showed improvements in perceived pain compared with baseline, although the change was not statistically significant from control group (-4.0[-5.0,0.4] vs. 0[-0.3,0.7], p = 0.087). There were significant improvements in pain with FREMS, assessed by McGill Pain questionnaire (p = 0.042) and Douleur neuropathique-4 questionnaire (p = 0.042). More participants on FREMS had greater than 30 percent reductions in perceived pain compared with controls [7/13(54%) vs 0/12(0%), p = 0.042] and significant improvements in Patient Global Impression of Change (p = 0.005). FREMS intervention had moderate benefits in quality of life, sleep, depression and pain medication use, but these were not statistically significant. FREMS might be used to treat individuals with PDPN inadequately controlled on two classes of neuropathic pain medications and is associated with improvements in pain severity and perceived impact of treatment. A larger, appropriately designed trial assessing its impact in this population is needed.


TP53 mutations in stage I gallbladder carcinoma with special attention to growth patterns.
32 stage I cases of gallbladder carcinoma (GC) were examined to evaluate TP53 mutations with special attention to growth patterns. Their growth patterns were classified into two types: polypoid (P-type) and flat (F-type). 16 cases of GC were classified as P-type and 16 as F-type. p53 immunohistochemistry was performed using a mouse monoclonal anti-p53 antibody. Mutations in exons 5-8 were examined by polymerase chain reaction single strand conformation polymorphism (PCR-SSCP) and direct sequencing. The incidence of p53 immunoreactivity was greater in the cases of F-type (11/16, 69%) than those in P-type (14/16, 25%) (P < 0.05). PCR-SSCP or direct sequencing revealed that TP53 mutations were detected in all cases positive for p53 protein. These results suggest that TP53 mutations may contribute to the carcinogenesis of the F-type GC, and than this pathway in the F-type may differ from that in the P-type GC.


A heparan sulfate-facilitated and raft-dependent macropinocytosis of eosinophil cationic protein.
Eosinophil cationic protein (ECP), a human RNAseA superfamily member, highly implicated in asthma pathology, is toxic to bronchial epithelial cells following its endocytosis. The mechanism by which ECP is internalized into cells is poorly understood. In this study, we show that cell surface-bound heparan sulfate proteoglycans serve as the major receptor for ECP internalization. Removal of cell surface heparan sulfate by heparinases or reducing glycan sulfation by chlorate markedly decreased ECP binding to human bronchial epithelial Beas-2B cells. In addition, ECP uptake and associated cytotoxicity were reduced in glycosaminoglycan-defective cells compared with their wild-type counterparts. Furthermore, pharmacological treatment combined with siRNA knockdown identified a clathrin- and caveolin-independent endocytic pathway as the major route for ECP internalization. This pathway is regulated by Rac1 and ADP-ribosylating factor 6 GTPases. It requires cholesterol, actin cytoskeleton rearrangement and phosphatidylinositol-3-kinase activities, and is compatible with the characteristics of raft-dependent macropinocytosis. Thus, our results define the early events of ECP internalization and may have implications for novel therapeutic design for ECP-associated diseases.


Differential effects of prostacyclin and prostaglandin E1 on bronchoconstriction and thrombocytopenia during collagen and arachidonate infusions and anaphylactic shock in the guinea-pig.
The antagonism by prostacyclin (PG12) and prostaglandin E1 (PGE1) of bronchoconstriction induced by serotonin (5HT), collagen, arachidonic acid (AA) and anaphylaxis, as well as of thrombocytopenia was studied in the guinea-pig. Under conditions where PGE1 prevented bronchoconstriction by 5HT, by collagen or by AA better than the accompanying thrombocytopenia, PG12 was a selective antagonist of bronchoconstriction due to collagen, but failed to interfere with that due to 5HT or to AA. Collagen-induced bronchoconstriction in the guinea-pig is platelet-dependent. PG12 blocks bronchoconstriction by collagen, because it prevents the platelet activation, and fails to interfere with bronchoconstriction by AA, even though it reduces the accompanying thrombocytopenia, because the role of platelets is negligible. PGE1 and PG12 failed to interfere with thrombocytopenia or with bronchoconstriction of anaphylactic shock, and were inactive even when the acute bronchial effect was suppressed by anti-histamine treatment. Anaphylactic thrombocytopenia is beyond the control of agents which stimulate the cyclic AMP system, and involves specific mechanism which are not stimulated in platelet-rich plasma.


Organohalogenated contaminants in eggs of rockhopper penguins (Eudyptes chrysocome) and imperial shags (Phalacrocorax atriceps) from the Falkland Islands.
In this study, we evaluated the use of seabird eggs of two common bird species from the Falkland Islands as bioindicators of contamination with organohalogenated contaminants (OHCs). We compared contamination levels and profiles of different OHCs between eggs of the rockhopper penguin (Eudyptes chrysocome) and the imperial shag (Phalacrocorax atriceps). In addition, laying order effects on OHC concentrations and profiles were also investigated in both species. For polychlorinated biphenyls (PCBs), organochlorine pesticides (OCPs) as well as polybrominated diphenyl ethers (PBDEs), concentrations were significantly lower in eggs of rockhopper penguins (27.6±0.70 ng/g lw, 56.5±1.33 ng/g lw and 0.98±0.04 ng/g lw, respectively) compared to the imperial shags (140±5.54 ng/g lw, 316±11.53 ng/g lw, 1.92±0.15 ng/g lw, respectively). On the other hand, 2'MeO-BDE 68 and 6MeO-BDE 47, two brominated compounds of reported natural origin, were significantly higher in the penguin eggs (0.55±0.05 ng/g lw and 7.01±0.64 ng/g lw, respectively) compared to the shag eggs (0.17±0.03 ng/g lw and 0.50±0.06 ng/g lw, respectively). In addition, PCB, OCP and PBDE contamination profiles differed markedly between the two species. Various factors, such as diet, feeding behaviour, migratory behaviour and species-specific metabolism, may be responsible for the observed results. For both rockhopper penguins and imperial shags, PCB, OCP and PBDE concentrations and profiles did not significantly change in relation to the laying order. This suggests that, for both species, any egg of a clutch is useful as a biomonitoring tool for OHCs. Although our results showed that OHCs have also reached the Falkland Islands, concentrations were relatively low compared to other studies. However, future monitoring may be warranted to assess temporal trends of different OHCs.


Efficacy of intravitreal dexamethasone implant in persistent diabetic macular edema after primary treatment with intravitreal ranibizumab.
To evaluate the efficiency and possible complications of intravitreal dexamethasone (IVD) implant in diabetic macular edema (DME) resistant to treatment of three consecutive intravitreal ranibizumab (IVR) injections. Fifty eyes of 38 patients were considered in this study. The best corrected visual acuity (BCVA), central macular thickness (CMT), and values of intraocular pressure (IOP) were examined preoperatively and postoperatively in the 1st, 2nd, 4th, and 6th months of IVD implantation. Twenty of the patients were women, and 18 of the patients were men. Mean age was 64.63 ± 7.15 (52-83) years. Mean number of IVR injection before IVD implantation was 3.4 ± 0.38. Mean BCVA (logMAR) was 0.874 ± 0.398 before IVD implantation, 0.598 ± 0.306 at the 1st month, 0.602 ± 0.340 at the 2nd month, 0.708 ± 0.359 at 4th month, and 0.800 ± 0.370 at 6th month. Mean of CMT was 519.700 ± 155.802 μm before IVD implantation, 274.000 ± 73.112 μm at the 1st month, 307.98 ± 87.869 μm at the 2nd month, 387.82 ± 110.503 μm at 4th month, and 478.54 ± 163.743 μm at 6th month. Improvements in BCVA and CMT were statistically significant (P < 0.05) at 1st, 2nd, and 4th months; however, these values were not statistically significant at 6 months. At 1st day, 1st and 2nd months, the values of IOP were increased significantly after IVD. Cataract progression was observed in just 1 of the 22 phakic patients. In DME resistant to treatment of consecutive IVR, IVD implantation has been observed to be effective in increasing BCVA and decreasing CMT in the first 3 months. IVD implantation can be considered an alternative method in the treatment of resistant DME.


Kinetic studies of cAMP-induced propagation of the allosteric signal in the cAMP receptor protein from Escherichia coli with the use of site-directed mutagenesis.
The cyclic AMP receptor protein (CRP) - general transcription factor in Escherichia coli - changes their conformation after the cAMP binding. For CRP mutants bearing the amino acids substitutions in position 138 located within the hinge region, the fluorescence stopped-flow measurements have been employed to study the kinetics of the conformational changes. By using two naturally appearing Tryptophan residues (W13, W85) localized nearby the ligand binding pocket and 1,5-I-AEDANS-labeled C178 localized in the helix-turn-helix (HTH) motif within the C-terminal domain as a fluorescence probes, we observed a first and a consensus steps of CRP-cAMP association, respectively. The collected data suggest that the kinetic parameters determined for mutants, reflect a component of the conformational change occurring in the native protein. Therefore, the independent association of two cAMP molecules to the wt protein is followed by at least a three-step conformational change which alters the surroundings of HTH motifs.


The presence of acyl-CoA: cholesterol acyltransferase in Tetrahymena pyriformis W.
1. The esterification of cholesterol was studied in Tetrahymena pyriformis an organism which does not synthesize sterols nor are sterols required for growth. 2. Microsomes catalyzed the esterification of cholesterol in the presence of oleoyl-CoA but not oleic acid or lecithin. 3. The enzyme has a similar sterol substrate specificity to that of mammalian acyl-CoA: cholesterol acyltransferase (ACAT) and was inhibited by the specific ACAT inhibitor 58-035. 4. The enzyme is constitutive since activity was observed in cells grown in sterol-free medium when cholesterol was added to the in vitro assay.


Role of Polycyclic Aromatic Alkylammonium Cations in Tuning the Electronic Properties and Band Alignment of Two-Dimensional Hybrid Perovskite Semiconductors.
Two-dimensional hybrid organic-inorganic perovskites (HOIPs) have recently drawn intense attention as potential photovoltaic materials. However, n = 1 two-dimensional (2D) HOIPs face the challenge of low conductivity between the inorganic layers, leading to unsatisfactory device performance. Interestingly, 2D HOIPs employing π-conjugated molecules as organic moieties show energy and charge transfers between organic and inorganic layers, indicating potentially efficient carrier transport for photovoltaic applications. Nevertheless, the development of 2D HOIP-based solar cells especially utilizing polycyclic aromatic alkylammonium as cations is in its infancy. Herein, we investigated the electronic structure and band alignment of a series of n = 1 2D Ruddlesden-Popper (RP) phase HOIPs containing different polycyclic aromatic groups and alkyl chains, based on density functional theory calculations. We find that the polycyclic aromatic group plays an important role in controlling the functionality of 2D HOIPs by directly modifying band-edge states, and the band alignment at the organic-inorganic interface can be designed to promote either exciton trapping or dissociation for light-emitting or photovoltaic applications, respectively.


[Presence of vitamin A and of rhodopsin in the eye of Lineus ruber (Heteronemert)].
In our experimental conditions, the positive Karli reaction in the microvilli of cells which seem to be visual and the localization of vitamin A in their area show that these cells are photosensitive.


Preparation and in vitro-in vivo evaluation of teniposide nanosuspensions.
Teniposide (TEN) is a potent, broad spectrum antitumor agent, especially for cerebroma. But the application in clinic was limited because of its poor solubility. In this paper, teniposide nanosuspensions drug delivery system (TEN-NSDDS) for intravenous administration was developed for the first time. Specifically, TEN nanosuspensions were prepared by an anti-solvent sonication-precipitation method and evaluated in comparison with teniposide injection (VUMON) in vitro and in vivo. TEN nanosuspensions prepared showed rod-like morphology and the size was 151 ± 11 nm with a narrow poly dispersion index 0.138 determined by dynamic light scattering. The obtained TEN nanosuspensions were physically stable at least 10 days at 4°C. And the freeze-drying preparations were stable during 3 months. The cytotoxicity of TEN nanosuspensions were considerable to that of VUMON against U87MG and C6 cells in vitro. When tested in rats bearing C6 tumors, the TEN concentration in the tumors treated by the nanosuspensions was more than 20 times than that by the TEN solution at 2h. The TEN nanosuspensions exhibited significant tumor growth inhibition. Overall, the results suggested that nanosuspensions was an alternative formulation for teniposide to be administered intravenously, and it would be a promising formulation in clinic.


[Pulmonary artery pressure sensor for ambulatory assessment of ventricular filling pressure in advanced heart failure : What should be considered for the follow-up care?]
Patients with advanced heart failure suffer from frequent hospitalizations. Noninvasive hemodynamic telemonitoring for assessment of pulmonary filling pressure has been shown to reduce hospitalizations. In this article, our experience with possible control intervals and the standardization of the follow-up care of hemodynamic telemonitoring is reported. A literature search and our own experience in the follow-up care concerning the implantable pulmonary artery pressure sensor for noninvasive hemodynamic telemonitoring in patients with advanced heart failure are presented. For standardized follow-up care of heart failure patients with hemodynamic monitoring a specialized team consisting of a heart failure nurse and heart failure physician is essential. These teams should ideally work based on a unique standard operating procedure (SOP) to ensure standardized control intervals and a standardized approach to classical hemodynamic changes. However, all therapeutic recommendations have to be prescribed by a physician and must be modified if individually appropriate. Optimized follow-up care for hemodynamically guided heart failure management requires the implementation of novel structures in the German health care system in order to transfer the clinical benefit from clinical trials into daily routine.


Spray-Congealing and Wet-Sieving as Alternative Processes for Engineering of Inhalation Carrier Particles: Comparison of Surface Properties, Blending and In Vitro Performance.
Traditionally, α-lactose monohydrate is the carrier of choice in dry powder inhaler (DPI) formulations. Nonetheless, other sugars, such as D-mannitol, have emerged as potential alternatives. Herein, we explored different particle engineering processes to produce D-mannitol carriers for inhaled delivery. Wet-sieving and spray-congealing were employed as innovative techniques to evaluate the impact of engineering on the particle properties of D-mannitol. To that end, the resulting powders were characterized concerning their solid-state, micromeritics and flowability. Afterwards, the engineered carrier particles were blended with inhalable size beclomethasone dipropionate to form low dose (1 wt%) DPI formulations. The in vitro aerosolization performance was evaluated using the NEXThaler®, a reservoir multi-dose device. Wet-sieving generated D-mannitol particles with a narrow particle size distribution and spray-congealing free-flowing spherical particles. The more uniform pumice particles with deep voids and clefts of wet-sieved D-mannitol (Pearl300_WS) were beneficial to drug aerosolization, only when used in combination with a ternary agent (10 wt% of 'Preblend'). When compared to the starting material, the spray-congealed D-mannitol has shown to be promising in terms of the relative increase of the fine particle fraction of the drug (around 100%), when used without the addition of ternary agents. The wet-sieving process and the related aerosolization performance are strongly dependent on the topography and structure of the starting material. Spray-congealing, has shown to be a potential process for generating smooth spherical particles of D-mannitol that enhance the in vitro aerosolization performance in binary blends of the carrier with a low drug dose.


Impact of diastolic Doppler indices on exercise capacity in hypertensive patients with electrocardiographic left ventricular hypertrophy (a LIFE substudy).
To assess whether Doppler evidence of impaired early diastolic relaxation during exercise is associated with lesser exercise capacity in hypertensive patients. Single center addition to the echocardiographic substudy in the Losartan Intervention For Endpoint (LIFE) reduction in hypertension study. University hospital out-patient clinic. A total of 60 patients (29 women and 31 men) with essential hypertension and electrocardiographic LV hypertrophy. Assessment of Doppler echocardiography and ergospirometry during semi-upright bicycling. Exercise capacity and its relation to diastolic Doppler indices at rest and during exercise. Average resting blood pressure was 181/97 +/- 18/9 mmHg, LV mass/body surface area 127 +/- 26 g/m2, midwall shortening 16 +/- 2%, and isovolumic relaxation time (IVRT) and transmitral early to atrial filling velocity (E/A) ratio 121 ms and 0.80, respectively. Exercise capacity, assessed as peak oxygen uptake and exercise load at exhaustion in all patients, were 20 and 25% higher, respectively, in men than women (both P < 0.01). In multivariate analysis, higher peak exercise load was related to male gender, higher E/A ratio at rest, greater reduction in IVRT during exercise and higher peak exercise heart rate (multiple R2 = 0.59, P < 0.01). Younger age, greater reduction in IVRT during exercise, higher midwall shortening and peak exercise heart rate were associated with higher peak oxygen uptake (multiple R2 = 0.47, P < 0.01). Diastolic LV performance significantly influences exercise capacity in hypertensive patients with LV hypertrophy. Impaired exercise capacity is more strongly associated with blunted reduction in IVRT during exercise than with lower E/A ratio at rest.


Metabolomics as a promising tool for improving understanding of multiple sclerosis: A review of recent advances.
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system that usually affects young adults. The development of MS is closely related to the changes in the metabolome. Metabolomics studies have been performed using biofluids or tissue samples from rodent models and human patients to reveal metabolic alterations associated with MS progression. This review aims to provide an overview of the applications of metabolomics that for the investigations of the perturbed metabolic pathways in MS and to reveal the potential of metabolomics in personalizing treatments. In conclusion, informative variations of metabolites can be potential biomarkers in advancing our understanding of MS pathogenesis for MS diagnosis, predicting the progression of the disease, and estimating drug effects. Metabolomics will be a promising technique for improving clinical care in MS.


Aspirin, Platelet P2Y12 Receptor Inhibitors, and Other Oral Antiplatelets: Comparative Pharmacology and Role in Elective PCI.
Angina pectoris accounts for a large burden of disease worldwide. Antiplatelet agents play a crucial role in inhibiting the platelet response to vascular injury after percutaneous coronary intervention (PCI) for the management of coronary artery disease. Antiplatelet agents are also essential in the longer term, because the metallic structure of stents is inherently thrombogenic. This article examines the use of aspirin, P2Y12 inhibitors, and other oral antiplatelets in the setting of elective PCI. Dual antiplatelet therapy in elective PCI is now standard therapy. The clinical use of novel antiplatelet therapy in the setting requires further evaluation.


Multicenter study of intravenous busulfan, cyclophosphamide, and etoposide (i.v. Bu/Cy/E) as conditioning regimen for autologous stem cell transplantation in patients with non-Hodgkin's lymphoma.
The current study aimed to evaluate the efficacy and toxicity of a combination of intravenous busulfan, cyclophosphamide and etoposide (i.v. Bu/Cy/E) as a conditioning regimen prior to autologous hematopoietic stem cell transplantation in patients with non-Hodgkin's lymphoma (NHL). Sixty-four patients with relapsed/refractory (n=36) or high-risk (n=28) lymphoma were enrolled. The high-dose chemotherapy consisted of i.v. Bu (0.8 mg kg(-1) i.v. q 6 h from day -7 to day -5), Cy (50 mg kg(-1) i.v. on day -3 and day -2) and E (400 mg m(-2) i.v. on day -5 and day -4). The median age was 43 (range 18-65) years, and 39 patients were male. Diffuse large B-cell lymphoma (40.6%) was the most common histological subtype. All evaluable patients achieved an engraftment of neutrophils (median, day 12) and platelets (median, day 13). Hepatic veno-occlusive disease was observed in four patients (three mild, one moderate grade), and two patients (3.1%) died from treatment-related complications. At a median follow-up of 16.4 months, 15 patients (23.4%) exhibited a relapse or progression, while 13 patients (20.3%) had died of disease. The estimated 3-year overall and progression-free survival for all patients was 72.1 and 70.1%, respectively. In conclusion, the conditioning regimen of i.v. Bu/Cy/E was well tolerated and seemed to be effective in patients with aggressive NHL.


Aging increases the expression of vasopressin receptors in both the kidney and urinary bladder.
The goal of this study was to determine whether aging effects the expression of V1a and V2 vasopressin receptors in the urinary bladder mucosa (UBM) and kidney. UBM and kidneys were obtained from young (3 months-of-age) and old (25-30 months-of-age) female Fisher 344 rats. Tissue samples were analyzed by western blotting for V1a and V2 receptor expression, and rat plasma levels of vasopressin levels were measured by ELISA. V1a and V2 receptors were detected in both the UBM and kidneys. Aging significantly (P < 0.05) increased the expression of V2 receptors by 2.80 ± 0.52 and 6.52 ± 1.24-fold in the UBM and kidneys, respectively. Aging also increased V1a receptor expression in the kidneys (5.52 ± 1.05 fold; P < 0.05), but not in the UBM. To the best of our knowledge, because this is the first detection of V2 receptors in the mammalian bladder mucosa, we also probed human UBM for V2 receptors and observed high expression in human UBM. Unlike V1a and V2 receptors, aging had only a minor effect on plasma vasopressin levels (8% increase). V2 receptors are substantially increased in the aging UBM. The role of these receptors in UBM is as yet undefined, but given their presence and action in the kidneys, the possible effect of these receptors in free water regulation should be considered. The large age-related increase in the expression of V2 receptors in both the UBM and kidney may contribute to the effectiveness of desmopressin in age-related nocturia.


Adductor spasmodic dysphonia: standard evaluation of symptoms and severity.
Description and quantification of the symptoms of adductor spasmodic dysphonia often reflect the clinician's knowledge of the disorder, ideas about the cause of the disorder, and personal experience. No reliable instrument that identifies and quantifies the spectrum of perceptual symptoms has been available. Therefore, we developed a standardized measure called the Unified Spasmodic Dysphonia Rating Scale (USDRS) in cooperation with a team of 118 experienced voice judges. Consensual validations of content validity guided the incremental development of the scale. Using the USDRS allows more consistent and complete data collection, both clinically and in research clinical trials.


Computer-assisted training as a complement in rehabilitation of patients with chronic vestibular dizziness--a randomized controlled trial.
To compare a computer-assisted home exercise program with conservative home-training following printed instructions in the rehabilitation of elderly patients with vestibular dysfunction. Single-blind, randomized, controlled trial. Geriatric department of a university hospital. Patients with chronic dizziness due to vestibular dysfunction (N=63) were randomly assigned to either rehabilitation in the clinic followed by computer-assisted home exercises (intervention group: n=32) or rehabilitation in the clinic followed by home exercises according to printed instructions (control group: n=31). Patients in the intervention group received assisted rehabilitation by a computer program. Measurements at baseline and at 8 and 16 weeks were compared. These included the One Leg Stand Test, Dynamic Gait Index, Chair Stand Test, Motion Sensitivity Test, Short Form-12, Dizziness Handicap Inventory, and visual analog scale. Both groups improved significantly during 16 weeks of rehabilitation. However, neither t tests nor repeated-measures analysis of variance demonstrated any significant differences between the 2 groups. The overall compliance rate to computer program exercises during 16 weeks was 57%. A computer-assisted program to support the home training of elderly patients with vestibular dysfunction did not improve rehabilitation more than did printed instructions.


Spirituality and quality of life in older adults: a path analysis model.
Study older adults' quality of life is becoming increasingly important in the assessment, quality improvement and allocation of health and social care service. The purpose of this study was to enhance knowledge on the relationship between modifiable (psychological variables) and non-modifiable variables (sociodemographic), and quality of life in elderly, regarding psychological and social variables in Portuguese context. This is a cross-sectional study, including 604 older adults from general community. 63.6% of the sample was composed by female gender with a mean age of 71.6(SD = 4.81). Participants completed the following instruments: Barthel Index to assess functionality; Satisfaction with Social Support Scale to assess social support; The Spiritual and Religious Attitudes in Dealing with Illness to assess spirituality and Short Form Health Survey 36, to assess mental and physical quality of life. A path analysis model was performed where the presence of a chronic disease, age and functionality has a direct effect on physical quality of life and spirituality had a direct effect on mental quality of life. Social support mediated the relationship between functionality and mental quality of life, and in turn, functionality mediated the relationship between age and physical quality of life. Results reinforce the effect of age and chronic disease as non-modifiable variables as well as functionality, spirituality and satisfaction with social support as modifiable variables, in the quality of life of older people. Social support, health and education programs in the community should be promoted in order to improve quality of life in this population. Strategies to promote functionality and enhance the social support network, especially in the elder with chronic illness, should be a priority.


Genetic mapping of a putative temperature-sensitive transcription mutation in Escherichia coli K12.
A putative temperature-sensitive transcription mutant described earlier (Jabbar and Jayaraman, 1976) has been genetically mapped. The locus maps at 38 min to the left of aroD. The mutation is recessive to the wild type and it affects a gene probably other than the genes coding for the alpha and beta subunits of phenylalanine tRNA synthetase and protein synthesis initiation factor IF-3 which also map in the same region.


Persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, in prolonging hepatic allografts in rats pretreated with a donor-specific blood transfusion.
A single intravenous injection of freshly heparinized blood from a donor-specific blood transfusion (DST) seven days before transplantation significantly prolongs the subsequent survival of hepatic allografts from ACI(RT1a) to LEW(RT1(1)) rats. We used W3/25 (anti-CD4) and OX22 (anti-CD45RC: an isoform of leukocyte-common antigen [CD45R]) monoclonal antibodies to investigate the cellular identity of hepatic allograft infiltrates following transplantation. The number of CD4+ and CD45RC+ cells in untreated allografts increased equally over time by day seven. However, in DST-treated hepatic allografts, CD4+ and CD45RC+ cells also increased over time by day 14, but the increment in the number of CD4+ cells was significantly greater than that in CD45RC+ cells. While the number of CD4+ cells remained persistently elevated in the hepatic allografts of rats pretreated with DST, they did not initiate rejection. Fluorescence-activated cell sorter (FACS) analysis revealed that the accumulated CD4+ T cells could be divided into two subsets, CD45RC- CD4+ and CD45RC+ CD4+ T cells, and that the ratio of CD45RC- CD4+/CD45RC+ CD4+ T cells in the hepatic allografts of recipients pretreated with DST was significantly greater than that in untreated allografts. Reverse-transcriptase polymerase chain reaction (RT-PCR) analysis demonstrated that CD45RC- CD4+ T cells expressed interleukin (IL)-4 and IL-10 messenger RNA (mRNA), but not IL-2 and interferon gamma (IFN-gamma). The pattern of messenger RNA expression in hepatic allograft infiltrates from animals pretreated with DST provides compelling evidence for the selective in vivo preservation of T-helper (Th2)-specific cytokines in the rat system. Our studies show that CD45RC leukocyte-common antigen expression can define different populations of hepatic infiltrating CD4+ T cells. A persistent infiltration of CD45RC- CD4+ T cells, Th2-like effector cells, is characteristic of hepatic allografts with a prolonged survival in DST-pretreated rats.


Adaptation of acyl-enzyme kinetic theory and an experimental method for evaluating the kinetics of fast-acting, irreversible protease inhibitors.
The theory of acyl-enzyme kinetics (Bender, M.L., Kézdy, F.J. and Wedler, F.C. (1967) J. Chem. Educ. 44, 84-88) has been adapted for use in evaluating the kinetics of inhibition of serine proteases by both natural and synthetic irreversible inhibitors. The new theory is based upon formal analysis of the case of an irreversible, active-site-directed inhibitor competing with an irreversible, active-site-directed substrate for the active site of a serine protease. From this theory, an experimentally simple and accurate method is described to obtain a second-order rate constant that is characteristic of the efficiency with which an irreversible inhibitor reacts. The experimental method is particularly useful for characterizing fast-acting, irreversible inhibitors. The theory and method which are applicable to a wide variety of enzymes are verified by analysis of the inhibition of bovine trypsin by three model inhibitors, p-nitrophenyl p'-guanidinobenzoate, soybean trypsin inhibitor and alpha-1-proteinase inhibitor as well as by human antithrombin III in the presence of heparin and by bovine pancreatic trypsin inhibitor.


Au Sputtered Paper Chromatography Tandem Raman Platform for Sensitive Detection of Heavy Metal Ions.
Surface-enhanced Raman scattering (SERS) is a powerful technique for sensitive detection, but it normally has difficulty in multicomponent detection in a complex system, especially for simultaneous analysis of mixture of heavy metal ions. In this work, a simple paper chromatography tandem SERS (PC-SERS) separation/detection platform is proposed by ion-sputtering gold on a filter paper. Based on SEM results, the great electromagnetic field inside nanogaps of Au nanoislands on the paper surface is evaluated with FDTD simulation. It is found that the PC-SERS platform has good uniformity (RSD = 10.12%) and long-time stability. The as-prepared PC-SERS platform was applied to efficiently separate and detect a mixture of pesticides (MG, MB, and CV) in pond water without any pretreatment process, and the limits of detection (LODs) were down to 10 nM. As a crucial application for food safety, several heavy metal ions such as Cd2+, Cu2+, and Ni2+ in grinded rice were successfully detected by the PC-SERS method taking advantage of the sandwich structure based on 4-mercaptobenzoic acid (4-MBA) molecules, which were modified onto sputtering the Au filter paper and gold nanoparticles (Au NPs) to link metal ions and acted as Raman signal molecules. All the LODs for metal ions were down to 1 μM. Due to the easiness of fabrication, good reproducibility, and simple pretreatment step, the PC-SERS platform holds promise in multicomponent detection in a real sample.


Higher epicardial fat in older adults living with HIV with viral suppression and relationship with liver steatosis, coronary calcium and cardiometabolic risks.
HIV infection is associated with ectopic fat deposition, which leads to chronic inflammation and cardiometabolic dysregulation. We assessed the epicardial adipose tissue (EAT) volume and its associated factors among people with HIV (PWH). A cross-sectional study. We conducted a cross-sectional study among PWH aged at least 50 years and age-matched and sex-matched HIV-negative older individuals in Bangkok, Thailand. Participants underwent a noncontrast, cardiac computed tomography (CT) scan to assess coronary artery calcium (CAC) score and EAT between March 2016 and June 2017. Multivariate linear regression analyses were used to investigate HIV-related factors, cardiac and metabolic markers associated with EAT volume. Median age was 55 years [interquartile range (IQR) 52-60] and 63% were men. Median duration of antiretroviral therapy (ART) was 16 years with 97% had HIV-1 RNA less than 50 copies/ml and median CD4 + cell count of 617 cells/μl. Median EAT volume was significantly higher in PWH [99 (IQR 75-122) cm 3 ] than HIV-negative individuals [93 (IQR 69-117) cm 3 ], P = 0.022. In adjusted model, factors associated with EAT volume included male sex ( P = 0.045), older age ( P < 0.001), abnormal waist circumference ( P < 0.001) and HOMA-IR ( P = 0.01). In addition, higher CAC score was independently associated with EAT volume. Higher mean EAT volume was seen in PWH with severe liver steatosis than those without steatosis ( P = 0.018). In adjusted PWH-only model, duration of HIV was significantly associated with higher EAT volume ( P = 0.028). In an aging cohort, PWH had higher EAT volume than HIV-negative controls. EAT was also independently associated with central fat accumulation, insulin resistance, liver steatosis and CAC score.


The Mixed Sellar Barrier: A New Subtype of this Novel Concept.
The use of the recent concept of sellar barrier revealed that a specific group of patients were difficult to categorize. For this reason, we propose to add a new subtype: the mixed sellar barrier. The aim of this work was to define the new mixed barrier subtype and analyze this in a series of operated patients. A retrospective study was carried out. From January to December 2018, 72 patients with pituitary adenomas underwent surgery by transsphenoidal approach. Patients with more than 1 surgery were excluded. Each patient's magnetic resonance imaging (MRI) was analyzed and classified using the following criteria: strong barrier (>1 mm), weak barrier (<1 mm), and mixed barrier (<1 mm in one region and >1 mm in another part). Mixed sellar barrier is the coexistence of 2 types of sellar barrier (strong and weak). The presence of a mixed sellar barrier on MRI was associated with the presence of a mixed sellar barrier intraoperatively (P < 0.0001). By using the new MRI classification that includes the mixed sellar barrier, we found a stronger statistically significant association regarding the risk of cerebrospinal fluid leak (for the extreme categories; i.e., strong and weak) compared to the original work. The new mixed sellar barrier subtype was precisely defined and illustrated. The correlation between MRI and intraoperative findings for this new subtype has been demonstrated in this study. A prospective study with a larger series of patients is required for validation.


Optical motion capture accuracy is task-dependent in assessing wrist motion.
Optical motion capture (OMC) systems are commonly used to capture in-vivo three-dimensional joint kinematics. However, the skin-based markers may not reflect the underlying bone movement, a source of error known as soft tissue artifact (STA). This study examined STA during wrist motion by evaluating the agreement between OMC and biplanar videoradiography (BVR). Nine subjects completed 7 different wrist motion tasks: doorknob rotation to capture supination and pronation, radial-ulnar deviation, flexion-extension, circumduction, hammering, and pitcher pouring. BVR and OMC captured the motion simultaneously. Wrist kinematics were quantified using helical motion parameters of rotation and translation, and Bland-Altman analysis quantified the mean difference (bias) and 95% limit of agreement (LOA). The rotational bias of doorknob pronation, a median bias of -4.9°, was significantly larger than the flexion-extension (0.7°, p < 0.05) and radial-ulnar deviation (1.8°, p < 0.01) tasks. The rotational LOA range was significantly smaller in the flexion-extension task (5.9°) compared to pitcher (11.6°, p < 0.05) and doorknob pronation (17.9°, p < 0.05) tasks. The translation bias did not differ between tasks. The translation LOA range was significantly larger in circumduction (9.8°) compared to the radial-ulnar deviation (6.3°, p < 0.05) and pitcher (3.4°, p < 0.05) tasks. While OMC technology has a wide-range of successful applications, we demonstrated it has relatively poor agreement with BVR in tracking wrist motion, and that the agreement depends on the nature and direction of wrist motion.


ER membrane protein complex 1 interacts with STIM1 and regulates store-operated Ca2+ entry.
Store-operated calcium entry (SOCE) is the process by which the emptying of endoplasmic reticulum (ER) Ca2+ stores causes an influx of Ca2+ across the plasma membrane (PM). It is the major Ca2+ influx pathway in nonexcitable cells and has a wide array of physiological functions. Upon store depletion, stromal interaction molecule 1 (STIM1), an ER calcium sensor relocates into discrete puncta at the ER-PM junction region, which results in the coupling of Ca2+ channels to initiate SOCE. However, the mechanism regulating STIM1 activity remains poorly understood. Here, we performed affinity purification of STIM1 and uncovered ER membrane protein complex 1 (EMC1) as an STIM1 binding partner. We showed that this interaction occurred in the ER through the intraluminal region of STIM1. After store depletion, EMC1 does not cluster adjacent to the PM, which suggests that it is distributed differently from STIM1. EMC1 knockdown with small interfering RNA resulted in a marked decrease in SOCE. Thus, these findings suggest that EMC1 functions as a positive regulator of SOCE.


Synthesis and pharmacological evaluation of novel substituted 9-deazaxanthines as A2B receptor antagonists.
A new series of 9-deazaxanthine derivatives with various substituents at the heterocyclic system were synthesized and evaluated for their binding affinities for the four human recombinant adenosine receptors, A(1)-A(3) subtypes. A number of the 9-deazaxanthines derivatives 3a-m showed moderate-to-high affinity for hA(2B) receptors, with compound 3f showing a 32-fold selectivity for A(2B) over A(1) and a 2750-fold selectivity for A(2B) over A(2A).


Cultivating Health in Martial Arts and Combat Sports Pedagogies: A Theoretical Framework on the Care of the Self.
"Martial arts and combat sports" (MACS) are a myriad of systems of embodied movements and underlying philosophy and pedagogies. Due to the intrinsic complexity of MACS, they have the potential to both reshape practitioners' selves and improve their wellbeing, as well as to hamper the pursuit of sustainable, healthy lifestyles. This article provides an interdisciplinary theoretical framework to critically approach both the "light" and the "dark" sides of martial pedagogies. The model we propose develops the Foucauldian notion of "the care of the self," which has been considerably overlooked in martial arts scholarship. Furthermore, by viewing health as a goal for cultivation, this proposal places the situated practices linked to materiality and discourses at the centre of the theoretical and empirical analyses. The article thus takes into account the internal diversity and cross-institutional variance of martial pedagogies by allowing scholars to explore four forms of cultivation (self, shared, social, ecological) prompted on a day-to-day basis. To conclude, we discuss the main methodological implications for multimodal research arising from the framework in order to foster future inquiries.


Atypical glandular cells: criteria to discriminate benign from neoplastic lesions and squamous from glandular neoplasia.
To evaluate the presence of some criteria in cervical smears with atypical glandular cells and their correlation with histological patterns to identify pre-neoplastic and neoplastic lesions. Seventy-three women referred with an atypical glandular cell smear, who had undergone conization or hysterectomy, were included in this study. Referral Pap smears were reviewed using the set of 27 cyto-morphological criteria that was correlated with the histological diagnosis. Histological results showed intraepithelial or invasive neoplasia in 35 (48%) cases and benign lesions in 38 (52%) cases. After logistic regression and decision tree analysis an increased nuclear/cytoplasmic ratio and the presence of dyskeratotic cells were strongly associated with intraepithelial or invasive neoplasia and the differential cyto-morphological criteria for glandular lesions were decreased cytoplasm, irregular nuclear membranes and the presence of nucleoli. The analysis of individual cyto-morphological criteria can better predict intraepithelial or invasive neoplasia and differentiate glandular from squamous lesions.


The Effect of Astaxanthin and Metformin on Oxidative Stress in Granulosa Cells of BALB C Mouse Model of Polycystic Ovary Syndrome.
Reactive oxygen species (ROS), involved in the pathogenesis of the polycystic ovary syndrome (PCOS), play a key role in the onset of apoptosis in follicles and granulosa cells (GCs). We aimed to investigate the antioxidant effects of AST and metformin separately and in combination on GCs using a PCOS mouse model. Forty-eight prepubertal female BALB C mice aged 25-30 days and weighing 12-14 g were studied. The PCOS model was created by subcutaneous injection of the dehydroepiandrosterone (DHEA) hormone in 8 mice of BALB C for 20 consecutive days. Apoptosis and the amount of ROS were evaluated in GCs of the ovaries via flow cytometry. The activity of AKT protein was measured by western blot, and the viability of GCs was investigated using spectrophotometry. Ovarian tissue sections were prepared, stained with H&E, and the morphology of the sections was examined. Statistical analysis was performed by SPSS v22.0 software using one-way ANOVA. We found that AST administration leads to a significant reduction in oxidative stress (P<0.01) and consequently a significant decrease in the rate of apoptosis (P<0.01). While the expression of AKT in the AST group revealed a significant increase (P<0.05), it decreased in the metformin group. However, it was still significantly higher than the control and PCOS groups. Ovulation was confirmed in both metformin and AST groups. Further studies are warranted to prove the efficacy of AST and to introduce it as a complementary therapeutic agent in PCOS.


Long-term maxillary three dimensional changes following maxillary protraction with or without expansion: A systematic review and meta-analysis.
Maxillary protraction with or without expansion appears to be an effective orthopedic treatment in skeletal class III growing patients, but the long-term effect on maxilla changes is less clear. The aim of this meta-analysis was to evaluate long-term three dimensional skeletal effects on maxilla through face mask (FM) with or without rapid maxillary expansion (RME) in skeletal CIII growing patients. We searched database including PubMed, Science Direct, Embase and Web of Science through Feb 2020. Inclusion criteria were randomized controlled trials or cohort studies recruiting growing patients who received maxillary protraction and/or expansion and comparing the treatment groups with untreated controls. The follow-up periods were more than 3 years. Risk of bias was assessed using the Cochrane tools (RoB2.0 and ROBINS-I). GRADE was used to qualify the evidence. This meta-analysis included 6 studies comprising 327 participants in total. No statistically significant changes were observed on the degree of Sella-Nasion-A point (SNA) in the treated groups when compared with the untreated controls. However, significant increase on maxillary rotation degree (mean difference: 8.20, 95% CI = 6.87-9.53, p < 0.001) and maxillary base width (mean difference: 2.27, 95% CI = 1.39-3.15, p < 0.001) in the treated groups, if compared with untreated controls. Our results indicated that FM and FM/RME treatments might not be long-term effective on correcting maxillary anteroposterior hypoplasia in growing patients. Additionally, more long-term studies are still necessary to further assess its skeletal benefits on maxilla in vertical and transverse dimension.


The effects of incorporating extended conversations into video-based story retelling instruction on oral narrative skills in adolescents with intellectual disability in China.
Oral narrative language is a persistent area of language difficulty for individuals with intellectual disability (ID). This study aims to explore the effectiveness of a comprehensive intervention program that incorporates extended conversations into video-based story retelling instruction with a novel visual support strategy, Story Hand, to develop oral narrative skills in adolescents with ID in China. Using a single-case multiple-probe across participants design, the researchers examined whether the comprehensive intervention program could improve participants' oral narrative skills both microstructurally and macrostructurally. All three participants demonstrated moderate to high treatment effects in the microstructural narrative outcomes (i.e., the mean length of utterance in morphemes [MLU-M] and the number of different words [NDW]) and one of the macrostructural narrative outcomes (i.e., the complexity of story grammar [SG-complexity]) in response to the comprehensive intervention program, and these acquired effects were maintained at a high level for up to one month. However, all three participants demonstrated limited treatment effects in one of the macrostructural narrative outcomes (i.e., cohesion) in response to the comprehensive intervention program. The comprehensive intervention program that incorporates extended conversations into visually supported video-based story retelling instruction offers an option for teachers to develop oral narrative skills in adolescents with ID. However, the relative effectiveness of the different components of the intervention needs to be further explored.


Detailed postal feedback about prescribing to asthma patients combined with a guideline statement showed no impact: a randomised controlled trial.
To evaluate the effects of postal feedback with clinically relevant data on general practitioners' prescribing compared with feedback with aggregate data on prescribing patterns of asthma drugs. The study was a randomised, controlled trial. The general practitioners (GPs) in the County of Funen, Denmark (292 GPs representing 178 practices) were randomised to one of three groups receiving different forms of prescriber feedback. The first group received detailed and clinically relevant data on asthma drug prescribing patterns and a guideline statement. These data included tables with counts of asthma patients following classification of each individual's consumption of inhaled beta2-agonists and use of inhaled steroids. The second group received aggregate data on asthma drug prescribing patterns and a guideline statement, and the third group received feedback on an unrelated subject and served as control for the other groups. Each GP received prescriber feedback three times within a 6-month period. The last two letters with prescriber feedback had updated information with the purpose of showing changes in prescribing patterns. Effects were followed for a period of 1 year. The main outcome measures were change in fraction of asthmatics treated with inhaled steroids and incidence rate of treatment with inhaled steroids. The three groups had similar baseline characteristics. None of the two types of feedback on prescribing of asthma drugs had a statistically significant impact on GPs' prescribing patterns. Mailed prescriber feedback of detailed and clinically relevant data with a guideline statement, without revealing patient identities, has little or no impact on prescribing patterns.


Evidence for the occurrence of specific iron (III)-binding compounds in near-shore marine ecosystems.
Aqueous extracts of samples from representtive types of near-shore marine ecosystems were examined for growth-promoting activity for the siderochrome auxotroph, Arthrobacter JG-9. Blue-green algal mat and sea grass samples gave strongly positive responses. Relative to Desferal (Ciba Pharmaceutical Co., Summit, N.J.), concentrations up to 110 ng/g (wet weight) of sample were found. In contrast, extracts of anaerobic muds or macroalgae gave no detectable activity. The hydroxamate type of iron chelator may be important in providing a form of iron in sea water readily utilized by the microalgae and marine higher plants.


Development of pH-responsive nanocomposites with remarkably synergistic antibiofilm activities based on ultrasmall silver nanoparticles in combination with aminoglycoside antibiotics.
Bacterial biofilms are responsible for many chronic infections because antibacterial agents exhibit poor penetration into the dense matrix barrier and cannot easily reach the internal bacteria. Herein, we reported pH-responsive nanocomposites (PDA@Kana-AgNPs) that could penetrate and disperse biofilms, which were synthesized by the combination of ultrasmall silver nanoparticles (AgNPs) and kanamycin, and then coating with polydopamine. Confocal fluorescence imaging indicated that PDA@Kana-AgNPs could respond to the acidic microenvironment of biofilms, leading to biofilm-triggered on- demand drug release in situ. The zone of inhibition test and Resazurin assay showed that the combination of kanamycin and AgNPs had greater antimicrobial activity against test strains (Staphylococcus aureus, Streptococcus pneumoniae, Pseudomonas aeruginosa, and Escherichia coli BL21) than when applied separately. The crystal violet staining test demonstrated that biofilms were effectively dispersed by the proposed nanocomposites. Biocompatibility was also evaluated, which showed that PDA@Kana-AgNPs were non-toxic to mammalian cells. Therefore, the proposed pH-responsive nanocomposites held great potential for efficient antibiotics delivery and showed synergistic antibacterial and antibiofilm activities. This strategy could also be used to encapsulate a variety of antibiotics in combination with other drugs or materials, thereby showing therapeutic potential in preventing biofilm-related infections and realizing fluorescence imaging in situ.


Denaturation by guanidinium chloride of dimeric MM-creatine kinase and its proteinase K-nicked form: evidence for a multiple-step process.
Cytosolic MM-creatine kinase is a homodimeric protein. Each monomer can be cleaved by proteinase K at an exposed surface loop, into two fragments K1 and K2, which remain associated. The nicked protein is thus a heterotetrameric protein, named (K1K2)2, made up of two heterodimers K1K2 linked together by their K1 subunit. In non-denaturing conditions, the cleaved protein does not present any measurable difference compared with uncleaved MM-creatine kinase, except for the loss of enzymatic activity. Comparative equilibrium denaturation of the two oligomeric proteins by guanidinium chloride indicates a multistep process with formation of either compact monomer or compact K1K2 dimer, a molten globule and a pre-molten globule state. In the case of the nicked-enzyme, the molten globule is composed of the two peptides K1 and K2, whereas in the pre-molten globule the interactions between K1 and K2 are too weak to maintain their cohesion. At low guanidinium chloride concentration, the proteinase K-nicked protein exhibits a higher accessibility of one of its tryptophan accompanied by a small decrease in its molar ellipticity suggesting a secondary structure loosening of the K1 peptide. Our results suggest that K1 and K2 are not strictly autonomous unfolding units and thus cannot be considered as independent domains.


LexFindR: A fast, simple, and extensible R package for finding similar words in a lexicon.
Language scientists often need to generate lists of related words, such as potential competitors. They may do this for purposes of experimental control (e.g., selecting items matched on lexical neighborhood but varying in word frequency), or to test theoretical predictions (e.g., hypothesizing that a novel type of competitor may impact word recognition). Several online tools are available, but most are constrained to a fixed lexicon and fixed sets of competitor definitions, and may not give the user full access to or control of source data. We present LexFindR, an open-source R package that can be easily modified to include additional, novel competitor types. LexFindR is easy to use. Because it can leverage multiple CPU cores and uses vectorized code when possible, it is also extremely fast. In this article, we present an overview of LexFindR usage, illustrated with examples. We also explain the details of how we implemented several standard lexical competitor types used in spoken word recognition research (e.g., cohorts, neighbors, embeddings, rhymes), and show how "lexical dimensions" (e.g., word frequency, word length, uniqueness point) can be integrated into LexFindR workflows (for example, to calculate "frequency-weighted competitor probabilities"), for both spoken and visual word recognition research.


Relative Conspicuity of Gadolinium-Based Contrast Agents in Interventional Pain Procedures.
To assess the relative radiographic conspicuity of gadolinium-based contrast agents (GBCAs) that may be used in spinal injection procedures when iodine-based contrast agents are contraindicated. Eight GBCAs and three iodinated agents of varying iodine concentrations were radiographed under conditions representative of lumbar spinal injections at four kilovoltage peak (kVp) values. Radiographic contrast of each agent was measured as the percent pixel value difference with respect to background. Gadobutrol (Gadovist, 1 mM/mL) had the highest radiographic contrast among the gadolinium agents tested. Measured radiographic contrast correlated with the molar concentration of gadolinium. Gadobutrol radiographic contrast lies between the contrast of iohexol concentrations of 240 and 140 mgI/mL. All agents have decreasing contrast as kVp increases, but GBCAs decrease less than iodine-based agents. Gadobutrol is the GBCA with the greatest conspicuity for use in spinal injection procedures. It also has the highest molar concentration of gadolinium, and potential neural toxicity from intrathecal delivery must be considered.


Characterization of early cytokine responses and an interleukin (IL)-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection.
Early infection with murine cytomegalovirus (MCMV) induces circulating levels of interleukin (IL)-12, interferon (IFN)-gamma, and tumor necrosis factor (TNF). Studies presented here further characterize these responses by defining kinetics and extending evaluation to include IL-1, IL-6, and glucocorticoids. IL-12 p40, IFN-gamma, TNF, IL-1alpha, and IL-6 were shown to be increased, but IL-1beta was undetectable, in serum of MCMV-infected mice. The IL-12 p40, IFN-gamma, TNF, and IL-6 responses were dramatic with peak levels reaching >150-10,000 pg/ml at 32-40 h after infection and rapidly declining thereafter. Glucocorticoid induction, peaking at 36 h and reaching 30-fold increases above control values, accompanied the cytokine responses. Mice with cytokine deficiencies or neutralized cytokine function demonstrated that IL-6 was the pivotal mediator of the glucocorticoid response, with IL-1 contributing to IL-6 production. The IL-6 requirement appeared to be specific for virus-type stimuli as the synthetic analogue of viral nucleic acid, polyinosinic-polycytidylic acid, also induced IL-6-dependent glucocorticoid release, but treatments with the bacterial product lipopolysaccharide and a non-immune physical restraint stressor elicited IL-6-independent responses. Collectively, the results identify IL-6 as a primary mediator of glucocorticoid induction, and elucidate specific pathways of interactions between immune and neuroendocrine systems during viral infection.


Discovery, synthesis, and pharmacological evaluation of spiropiperidine hydroxamic acid based derivatives as structurally novel histone deacetylase (HDAC) inhibitors.
New spiro[chromane-2,4'-piperidine] and spiro[benzofuran-2,4'-piperidine] hydroxamic acid derivatives as HDAC inhibitors have been identified by combining privileged structures with a hydroxamic acid moiety as zinc binding group. The compounds were evaluated for their ability to inhibit nuclear extract HDACs and for their in vitro antiproliferative activity on different tumor cell lines. This work resulted in the discovery of spirocycle 30d that shows good oral bioavailability and tumor growth inhibition in an HCT-116 murine xenograft model.


Growth of mammary epithelial cells from neonatally sex hormone-exposed mice in serum-free collagen gel culture.
Neonatal sex hormone treatments are known to cause an increase in mammary tumors in female mice with expressed mammary tumor virus (MTV). The growth of mammary epithelial cells from mice treated neonatally with sex hormones was studied in response to growth-stimulatory factors in a serum-free collagen gel culture system which sustains the growth of normal mammary epithelial cells. Animals were treated with hormones or oil-vehicle for the first 5 days after birth. Cells from control mice at 2 and 3 months of age showed a maximal growth response to insulin at 5-10 micrograms/ml and LiCl at 5-20 mM. Cells responded to epidermal growth factor at all concentrations used (1, 10 and 50 ng/ml). In contrast, mammary epithelial cells from mice treated neonatally with estrogen (estradiol and diethylstilbestrol (DES] showed a reduced growth response to the growth factors tested.


Measurement and Visualization of Tight Rock Exposed to CO2 Using NMR Relaxometry and MRI.
Understanding mechanisms of oil mobilization of tight matrix during CO2 injection is crucial for CO2 enhanced oil recovery (EOR) and sequestration engineering design. In this study exposure behavior between CO2 and tight rock of the Ordos Basin has been studied experimentally by using nuclear magnetic resonance transverse relaxation time (NMR T2) spectrum and magnetic resonance imaging (MRI) under the reservoir pressure and temperature. Quantitative analysis of recovery at the pore scale and visualization of oil mobilization are achieved. Effects of CO2 injection, exposure times and pressure on recovery performance have been investigated. The experimental results indicate that oil in all pores can be gradually mobilized to the surface of rock by CO2 injection. Oil mobilization in tight rock is time-consuming while oil on the surface of tight rock can be mobilized easily. CO2 injection can effectively mobilize oil in all pores of tight rock, especially big size pores. This understanding of process of matrix exposed to CO2 could support the CO2 EOR in tight reservoirs.


COX-2 inhibition affects growth rate of Chlamydia muridarum within epithelial cells.
Chlamydiae alter apoptosis of host target cells, which regulates their growth. Cyclooxygenase-2 (COX-2), the rate-limiting enzyme for prostaglandin E2 (PGE2) production, modulates epithelial cell survival. We addressed whether endogenous PGE2 alters chlamydial growth or apoptosis of epithelial cells infected with Chlamydia muridarum. PGE2 is secreted by infected host cells in the genital tract (GT). Using immunohistochemical techniques, we found that COX-2 enzyme was localized to epithelial cells in the GT in vivo. Pellets of the COX-2 enzyme inhibitor, NS-398, and placebo were implanted in mice subcutaneously and released a constant amount of these chemicals throughout the infection. NS-398-treated mice were found to exhibit 10-fold lower bacterial load than the placebo group on day 3 post infection, suggesting disruption of the chlamydial developmental cycle. To prove this, the human lung adenocarcinoma cell line A549 was then infected with different MOIs of C. muridarum in the presence of multiple concentrations of NS-398 in vitro. There was no difference in inclusion forming units (IFUs) between NS-389-treated and untreated cells. We also found no alterations in C. muridarum IFUs in A549 cells transfected with a 2.0 kb cDNA fragment of human COX-2 cloned in the sense (S) or anti-sense (AS) orientation. However, the inclusion size was reduced and the number of EB was significantly diminished during reinfection in AS-transfected cells. In addition, the absence of COX-2 did not significantly modify apoptosis in infected cells. In total, COX-2 deficiency reduces the infectious burden in vivo and may modulate transmission of the organism.


Recent high school graduates support mandatory cardiopulmonary resuscitation education in Australian high schools.
To evaluate recent high school graduates' opinions on mandatory cardiopulmonary resuscitation (CPR) training in the high school curriculum as a solution to improving bystander CPR rates. Participants completed questionnaires assessing their CPR training history during their high school education, their willingness to learn CPR during their high school years and their opinion on making CPR training mandatory for high school curricula. Of the 178 participants in this study, 60% had undertaken CPR training during their high school education. Of those who had not undertaken CPR training, 75% reported that they would have been willing to learn CPR had they been provided with the opportunity. A total of 97% of participants were in support of mandatory CPR training in high school education. Implementing mandatory CPR training in high school education would be embraced by students. Implications for public health: Findings of this study support our recommendation to implement mandatory CPR training in the high school curriculum. This will likely increase the number of bystanders in the community who would spontaneously administer CPR, thereby improving outcomes for patients experiencing out-of-hospital cardiac arrest.


[The psychosomatic-gynecological outpatients department of the II. Gynecological Clinic of the University of Vienna (author's transl)].
A report is given on the organization and practice of an outpatients departments for psychosomatics in gynecology. The data of 284 patients concerning social status, possible trigger mechanisms (life events), diagnosis and treatment are presented. The applied therapeutic technique can be described as client centered counselling basing on psychoanalytic theory. the importance of cooperation between psychotherapist and gynecologist to the woman's benefit is emphasized.


Recycled water for stream flow augmentation: benefits, challenges, and the presence of wastewater-derived organic compounds.
Stream flow augmentation with recycled water has the potential to improve stream habitat and increase potable water supply, but the practice is not yet well understood or documented. The objectives of this report are to present a short review illustrated by a case study, followed by recommendations for future stream flow augmentation projects. Despite the fact that wastewater discharge to streams is commonplace, a water agency pursuing stream flow augmentation with recycled water will face unique challenges. For example, recycled water typically contains trace amounts of organic wastewater-derived compounds (OWCs) for which the potential ecological risks must be balanced against the benefits of an augmentation project. Successful stream flow augmentation with recycled water requires that the lead agency clearly articulate a strong project rationale and identify key benefits. It must be assumed that the public will have some concerns about water quality. Public acceptance may be better if an augmentation project has co-benefits beyond maintaining stream ecosystems, such as improving water system supply and reliability (i.e. potable use offset). Regulatory or project-specific criteria (acceptable concentrations of priority OWCs) would enable assessment of ecosystem impacts and demonstration of practitioner compliance. Additional treatment (natural or engineered) of the recycled water may be considered. If it is not deemed necessary or feasible, existing recycled water quality may be adequate to achieve project goals depending on project rationale, site and water quality evaluation, and public acceptance.


Cross-cultural Adaptation and Validation of Hindi Version of Child Oral Impacts on Daily Performance Index.
Oral diseases may have an impact on quality of life (QoL) and the oral health-related quality of life (OHRQoL). As compared to clinical measures which are unable to provide a complete picture, OHRQoL indices quantify the oral health impact on overall health. Worldwide indices have been developed to measure the OHRQoL in children but none can be applicable in Indian context. The aim of the study was cross-cultural adaptation and psychometric analysis of Hindi version of child oral impacts on daily performance (C-OIDP) index. Translation and back translation were done for index using prescribed guidelines for cross-cultural adaptation. A pilot study was conducted in 32 children and required modifications were done. The final Hindi version was tested for reliability and validity on a convenience sample of 64 children aged 11-14 years selected from public schools in Delhi. The psychometric properties of the Hindi version were tested for face, content, construct validity along with internal consistency, and test-retest reliability. The mean age of the final sample (n = 64) was 13.02 ± 0.93 years with boys (51.6%) and girls (48.4%). The mean C-OIDP score was 8.8 ± 7.8. Significant association was obtained when C-OIDP was compared with self-perceived oral health. Interitem correlation ranged from -0.008 to 0.45. Kappa for categories of child OIDP ranged from 0.711 to 1.00 and intraclass correlation coefficient was 0.91. The Hindi version of C-OIDP is a valid and reliable tool to measure OHRQoL in Hindi-speaking children in India. Chahar P, Mohanty V, Balappanavar AY, et al. Cross-cultural Adaptation and Validation of Hindi Version of Child Oral Impacts on Daily Performance Index. Int J Clin Pediatr Dent 2020;13(2):124-129.


The gastrointestinal tract is critical to the pathogenesis of acute HIV-1 infection.
It has become evident that the gastrointestinal tract is preferentially and profoundly depleted of CD4+ T cells during acute HIV-1 infection. The enhanced susceptibility of gastrointestinal lymphoid tissue to HIV-1 is in part due to the large complement of CCR5+ memory CD4+ T cells resident at this site. Here we summarize the recent findings demonstrating that the gastrointestinal tract plays a critical role in the pathogenesis of acute HIV-1 and simian immunodeficiency virus infections. Ongoing work in this field is likely to have a significant effect on HIV research in the near future.


Endodontic radiography: who is reading the digital radiograph?
Digital radiographic imaging systems have undergone tremendous improvements since their introduction. Advantages of digital radiographs over conventional films include lower radiation doses compared with conventional films, instantaneous images, archiving and sharing images easily, and manipulation of several radiographic properties that might help in diagnosis. A total of 6 observers including 2 endodontic residents, 3 endodontists, and 1 oral radiologist evaluated 150 molar digital periapical radiographs to determine which of the following conditions existed: normal periapical tissue, widened periodontal ligament, or presence of periapical radiolucency. The evaluators had full control over the radiograph's parameters of the Planmeca Dimaxis software program. All images were viewed on the same computer monitor with ideal vie-wing conditions. The same 6 observers evaluated the same 150 digital images 3 months later. The data were analyzed to determine how well the evaluators agreed with each other (interobserver agreement) for 2 rounds of observations and with themselves (intraobserver agreement). Fleiss kappa statistical analysis was used to measure the level of agreement among multiple raters. The overall Fleiss kappa value for interobserver agreement for the first round of interpretation was 0.34 (P < .001). The overall Fleiss kappa value for interobserver agreement for the second round of interpretation was 0.35 (P < .001). This resulted in fair (0.2-0.4) agreement among the 6 raters at both observation periods. A weighted kappa analysis was used to determine intraobserver agreement, which showed on average a moderate agreement. The results indicate that the interpretation of a dental radiograph is subjective, irrespective of whether conventional or digital radiographs are used. The factors that appeared to have the most impact were the years of experience of the examiner and familiarity of the operator with a given digital system.


'We're in this together': A content analysis of marketing by alcohol brands on Facebook and Instagram during the first UK Lockdown, 2020.
The closure of on-licence premises and the restrictions placed on citizen's movements and leisure to address the COVID-19 pandemic in 2020, created an unprecedented situation for the alcohol industry. With the availability and supply of alcohol being restricted, and the social context of alcohol use transformed, alcohol corporations were required to adapt their marketing materials and actions in response. A content analysis of alcohol marketing by 18 alcohol brands on Facebook and Instagram during the first UK national lockdown (from 17th March- 4th July 2020) was conducted. Comments left by social media followers on posts advertising what could be defined as brand COVID-19 Corporate Social Responsibility (CSR) initiatives (i.e. monetary donations, production of hand sanitiser) were thematically analysed. Alcohol brands quickly adapted to the changing social, economic and health context of the global pandemic. Changes to the availability and sale of alcohol were evident, with brands encouraging the stockpiling of alcohol as an essential item through predominantly online sales and delivery services. Brands also adapted to the changing social and physical context of alcohol use and intensified encouragement of home drinking. Messages of togetherness underpinned the promotion of virtual interactions, for which alcohol use was presented as a key component. Consumers were encouraged to contribute to pandemic responses by 'staying at home', and consuming alcohol. Importantly, COVID-19 provided a useful marketing opportunity for alcohol producers to present themselves as private partners to a primarily public sector response, through innovative CSR initiatives such as philanthropic donations to help prevent the transmission of COVID-19. An inductive thematic analysis of online comments on CSR posts found that such activities were interpreted by consumers as ethical actions, and that they reinforced positive brand image and loyalty amongst existing and new consumers. Alcohol corporations are highly resilient in times of crises and the brands analysed were able to quickly adapt their marketing to the COVID-19 pandemic. Future research is required to examine whether these profitable strategies are maintained post pandemic.