Human Corticotropin-Releasing Hormone Tests: 10 Years of Real-Life Experience in Pituitary and Adrenal Disease.
The human corticotropin-releasing hormone (CRH) test (hCRHtest) is used to differentiate Cushing disease (CD) from ectopic adrenocorticotropin (ACTH) secretion (EAS), to assess autonomous cortisol secretion by the adrenal glands, and to characterize pseudo-Cushing syndrome (CS) or adrenal insufficiency (AI). The main outcome measure of this study was to assess the diagnostic accuracy of the hCRHtest. We measured ACTH and cortisol levels; collected the peak values (peakACTH and peakcortisol), and calculated the percentage increases (∆%ACTH and ∆%cortisol) after an intravenous bolus of 100 μg hCRH. This cross-sectional study of hCRH tests from 2010 to 2019 took place in a referral university hospital center. We enrolled 200 patients: 86 CD, 15 EAS, 18 adrenal CS, 25 mild adrenal autonomous cortisol secretion, 31 pseudo-CS, and 25 suspected AI. The hCRHtest was performed mainly for the differential diagnosis of ACTH-dependent CS or adrenal lesions (P = .048). PeakACTH and peakcortisol were higher in CD, and ∆%ACTH and ∆%cortisol were able to differentiate CD from EAS with a sensitivity and specificity greater than 80%. In patients with low (< 10 pg/mL) or indeterminate (10-20 pg/mL) basalACTH levels, an absent or reduced peakACTH response was able to differentiate adrenal from ACTH-dependent forms. PeakACTH and peakcortisol after hCRHtest were lower in pseudo-CS than in CD, but ∆%ACTH and ∆%cortisol were similar. The role of hCRHtest in patients with AI was limited. The hCRHtest test is the mainstay of the differential diagnosis of ACTH-dependent CS. It is also useful for pointing to a diagnosis of CD in the event of bilateral adrenal masses, and in patients with low basalACTH.


Regional distribution of neural cell adhesion molecule (N-CAM) and L1 in human and rodent hippocampus.
Cell surface adhesion molecules N-CAM and L1 are implicated in central nervous system (CNS) cell migration and axon outgrowth in in vitro and in vivo developmental studies. These molecules show a differential distribution during CNS development, thus suggesting that they subserve different roles in process outgrowth and tissue organization. A variety of N-CAM isoforms are known, and individual N-CAMs undergo posttranslational modification. Such changes and the potential for generating numerous molecules may mediate development of specific neural cell contacts and circuitry. We evaluated immunohistochemical staining of polyclonal antibodies to L1 and N-CAM, as well as monoclonal antibodies directed against embryonic N-CAM and the 140 and 180 kDa species of N-CAM in human, rat, and mouse hippocampus. Staining patterns in the three species were qualitatively similar, but staining in the mouse hippocampus was quantitatively greater for some epitopes. A distinctive pattern of staining was found, corresponding to the known anatomy of the structure. Total N-CAM staining was intense in the hilus and inner molecular layer (ML) of the dentate gyrus with lighter staining in the dentate outer ML. The mossy fiber tract (MFT), comprising axons traveling from the dentate granule cells to CA3 pyramidal cells, was strongly stained by polyclonal antibody to N-CAM. There was abundant staining of the stratum radiatum (SR) and stratum oriens (SO) of CA1, but stratum lacunosum moleculare (LM) showed very little staining. The monoclonal antibody 12F11, which recognizes the 140 and 180 kDa forms of N-CAM, intensely stained the MFT, hilus, and inner ML.(ABSTRACT TRUNCATED AT 250 WORDS)


Mechanism of action for N-substituted benzamide-induced apoptosis.
We have analysed the mechanism of action for induction of apoptosis by N-substituted benzamides using declopramide as a lead compound. We show here that declopramide at doses above 250 microM in the mouse 70Z/3 pre-B cell line or in the human promyeolocytic cancer cell line HL60 induced cytochrome c release into the cytosol and caspase-9 activation. The broad spectrum caspase inhibitor zVADfmk and caspase-9 inhibitor zLEDHfmk inhibited apoptosis and improved cell viability when administrated to cells 1 h before exposure to declopramide, whereas the caspase-8 inhibitor zIEDHfmk had less effect. Also, the over expression of Bcl-2 by transfection in 70Z/3 cells inhibited declopramide-induced apoptosis. Prior to the induction of apoptosis, a G(2)/M cell cycle block was induced by declopramide. The cell cycle block was also observed in the presence of broad spectrum caspase inhibitor zVADfmk and in a transfectant expressing high levels of Bcl-2. Furthermore, while p53 was induced in 70Z/3 cells by declopramide, neither the apoptotic mechanism nor the G(2)/M cell cycle block were dependent on p53 activation since both effects were also seen in p53 deficient HL60 cells after addition of declopramide.


A novel electrochemiluminescence sensor based on Ru(bpy)₃²⁺/N-doped carbon nanodots system for the detection of bisphenol A.
A novel Ru(bpy)3(2+)-based electrochemiluminescence (ECL) sensing platform, using N-doped carbon nanodots (N-C dots) as co-reactant, was established for the sensitive and selective detection of bisphenol A (BPA). N-C dots not only could enhance the ECL signal, but also significantly improved the reproducibility and stability of Ru(bpy)3(2+) ECL system. The developed ECL sensing system was sensitive to detect BPA based on its efficient quenching effect on Ru(bpy)3(2+)/N-C dots. The N-C dots-enhanced ECL mechanism and BPA-quenched ECL mechanism were investigated. Under the optimum conditions, the inhibited ECL intensity was in good linear relationship versus the concentration of BPA in the range of 0.03-1.0 μM with the detection limit of 10 nM. The relative standard deviation (RSD) for 25 successive measurements with one sensor was 1.1% and for eight different sensors was 2.5%, respectively. The fabricated sensing platform was successfully applied for the detection of BPA in baby bottle and nipple, and relatively satisfactory recoveries were obtained.


Efficacy of tocilizumab in two patients with anti-TNF-alpha refractory uveitis.
To report on two patients with refractory uveitis treated with tocilizumab; a new humanized monoclonal antibody against the interleukin-6 receptor (IL-6R). Retrospective interventional case series. Both patients received a monthly infusion of tocilizumab 8 mg/kg; associated with corticosteroids. Outcome measures were visual acuity and central retinal thickness evaluated with optical coherence tomography. An improvement in visual acuity and a decrease in macular edema were observed in these two patients. Tocilizumab seems to be a promising treatment in refractory uveitis. A prospective study is needed to evaluate the role of this new agent in the management of refractory uveitis.


Reversible inhibition of poxvirus replication by cycloheximide during the early phase of infection.
Infection of primary chick embryo fibroblasts with Vaccinia WR, IHD-W, and cowpox virus even at high m.o.i. does not cause drastic early inhibition of host cell protein synthesis. This contrasts with the infection by these viruses of many eucaryotic cells. Cellular protein synthesis of mouse L cells is also only partially inhibited after infection with cowpox virus up to a m.o.i. of 2500 e.b. As predicted by Moss and Filler (1970, J. Virol. 5, 99-108) no irreversible inhibition of poxvirus replication is observed in these cells following the addition of cycloheximide early after infection. The viral cores which accumulate in chick embryo fibroblasts in the presence of cycloheximide are further uncoated after removal of the protein synthesis inhibitor. These poxvirus host cell systems can be used to identify in vivo immediate and putative delayed early viral gene products. Formation of progeny virus, viral DNA synthesis, the sequential formation of viral proteins, and sensitivity to interferon has been demonstrated in chick embryo fibroblasts after reversal of the cycloheximide block. These studies indicate a synchronized replication cycle of poxvirus after reversal of the cycloheximide block.


Septic patients with mitochondrial DNA haplogroup JT have higher respiratory complex IV activity and survival rate.
The influence of mitochondrial deoxyribonucleic acid (mtDNA) haplogroup or oxidative phosphorylation system (OXPHOS) function on survival of septic patients has been scarcely studied. However, the association between mtDNA haplogroup, OXPHOS capacity at diagnosis of severe sepsis, and survival has been not previously reported, and that was the objective of the present study. This was a prospective, multicenter, observational study. Blood samples from 198 patients at diagnosis of severe sepsis were analyzed to determine mtDNA haplogroup and platelet respiratory complex IV (CIV) specific activity. The end point of the study was 30-day survival. Septic patients with mtDNA haplogroup JT showed higher 30-day survival than those with mtDNA haplogroup non-JT (31/38 [81.6%] vs 99/160 [61.9%]; P= .02). Septic patients with mtDNA haplogroup JT showed higher platelet CIV specific activity than those with mtDNA haplogroup non-JT (P= .002). The main novel finding of our study, including the largest series providing data on platelet CIV specific activity according to mtDNA haplogroup in severe septic patients, was that those with mtDNA haplogroup JT showed higher survival and higher platelet CIV specific activity at diagnosis of severe sepsis than patients with mtDNA haplogroup non-JT.


Functional and proteomic analysis of submandibular saliva in rats exposed to chronic stress by immobilization or constant light.
In this study, we have evaluated the effects of stress on functional and proteomic changes in submandibular saliva of rats. Male adult rats were divided in three groups: IMO (2 h/day of immobilization for 7 days), LL (constant light during 20 days), C (unstressed controls submitted to 14 h light-10h dark cycle). Body weight, food intake and the dry weight of submandibular gland were recorded. Saliva samples, collected under anaesthesia following i.p. administration of isoproterenol and pilocarpine (5 mg/kg), were assayed for total proteins (TP), amylase activity and SDS-PAGE electrophoresis. Body weight, food intake and the dry weight of submandibular gland of IMO rats were lower than those of C and LL groups. The salivary volumes secreted in IMO and LL rats, were significantly higher than in controls. The TP output (μg protein/μg saliva/mg of dry tissue) and amylase activity output (AU/μg of saliva/mg of dry tissue) in IMO were significantly higher than in C and LL animals. The electrophoretic pattern of saliva proteins of LL rats, revealed the absence of a protein band of approximately 25 kDa. This band was composed by the common salivary protein-1 and a prolactin-induced protein as identified by peptide mass fingerprinting. Differences in body weight and food intake between IMO and LL might be attributed to the sort and intensity of stressors stimuli. The changes in the volume of secreted saliva could be a compensatory mechanism in response to stressors. The increase of total protein in IMO rats and the absence of 25 kDa proteins in LL, would suggest that the submandibular glands respond to the sympathetic nervous system stimuli induced by the stress with an increase of activity of the sympathetic nerves in IMO and a reduction in LL rats.


Pacemaker therapy in premature children with high degree AV block.
The smallest pacemaker pulse generator and a steroid-eluting bipolar epicardial lead were implanted in two premature children with symptomatic AV block. Stable capture threshold and high amplitude evoked response electrogram resulted in normal function of the pacemaker Autocapture algorithm, which adjusts output 0.3 V above the measured capture threshold. Autocapture had previously been used only with endocardial leads. Longer-term observation is required.


The Bromodomain Protein 4 Contributes to the Regulation of Alternative Splicing.
The bromodomain protein 4 (BRD4) is an atypical kinase and histone acetyl transferase (HAT) that binds to acetylated histones and contributes to chromatin remodeling and early transcriptional elongation. During transcription, BRD4 travels with the elongation complex. Since most alternative splicing events take place co-transcriptionally, we asked if BRD4 plays a role in regulating alternative splicing. We report that distinct patterns of alternative splicing are associated with a conditional deletion of BRD4 during thymocyte differentiation in vivo. Similarly, the depletion of BRD4 in T cell acute lymphoblastic leukemia (T-ALL) cells alters patterns of splicing. Most alternatively spliced events affected by BRD4 are exon skipping. Importantly, BRD4 interacts with components of the splicing machinery, as assessed by both immunoprecipitation (IP) and proximity ligation assays (PLAs), and co-localizes on chromatin with the splicing regulator, FUS. We propose that BRD4 contributes to patterns of alternative splicing through its interaction with the splicing machinery during transcription elongation.


Synergistic activities of moxifloxacin combined with piperacillin-tazobactam or cefepime against Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii clinical isolates.
The bactericidal activity of moxifloxacin alone and in combination with cefepime or piperacillin-tazobactam against clinical isolates of Klebsiella pneumoniae, Enterobacter cloacae, and Acinetobacter baumannii was evaluated by using time-kill methods and antimicrobial concentrations of one-half and one times the MIC. Synergy was observed in 58 to 88% of the strains and resulted in bactericidal activity against 60 to 100% of the strains. Combinations including moxifloxacin demonstrated enhanced bactericidal activity compared with that of either agent tested alone.


Efficiency of foam fractionation for the enrichment of nonpolar compounds from aqueous extracts of plant materials.
Biologically active compounds from several useful plants were enriched using foam fractionation, a separatory method belonging to the adsorptive bubble separation (ABS). Nonpolar humulones (1-6) from Pilsener beer, curcuminoids (7-9) from turmeric, and carotenoids (16 and 17) from carrot juice were enriched fast and quantitatively, depending on the process parameters, whereas more polar compounds such as catechins from green tea (11, 12, 14, and 15) and naringin (18) and hesperidin (19) from orange and grapefruit juices could not be enriched.


Evolution of class-specific peptides targeting a hot spot of the Galphas subunit.
The four classes of heterotrimeric G-protein alpha subunits act as molecular routers inside cells, gating signals based on a bound guanosine nucleotide (guanosine 5'-triphosphate versus guanosine 5'-diphosphate). Ligands that specifically target individual subunits provide new tools for monitoring and modulating these networks, but are challenging to design due to the high sequence homology and structural plasticity of the Galpha-binding surface. Here we have created an mRNA display library of peptides based on the short Galpha-modulating peptide R6A-1 and selected variants that target a convergent protein-binding surface of Galphas.guanosine 5'-diphosphate. After selection/evolution, the most Galphas-specific peptide, Galphas(s)-binding peptide (GSP), was used to design a second-generation library, resulting in several new affinity- and selectivity-matured peptides denoted as mGSPs. The two-step evolutionary walk from R6A-1 to mGSP-1 resulted in an 8000-fold inversion in binding specificity, altered seven out of nine residues in the starting peptide core, and incorporated both positive and negative design steps. The resulting mGSP-1 peptide shows remarkable selectivity and affinity, exhibiting little or no binding to nine homologous Galpha subunits or human H-Ras, and even discriminates the Galphas splice variant Galphas(l). Selected peptides make specific contacts with the effector-binding region of Galpha, which may explain an interesting bifunctional activity observed in GSP. Overall, our work demonstrates a design of simple, linear, highly specific peptides that target a protein-binding surface of Galphas and argues that mRNA display-based selection/evolution is a powerful route for targeting protein families with high class specificity and state specificity.


[Compensatory mechanisms regulating oxygen transport and erythropoiesis during an alteration in the erythrocyte composition of the blood in rats].
The data obtained revealed that the level of 2,3-DPH in erythrocytes and that of erythropoietin in the blood plasma were important compensatory mechanisms for regulation of the oxygen transport and the erythropoiesis in alteration of the blood erythrocyte composition in rats.


Anterior chamber depth measurement using the split-lamp microscope.
I devised a new and simple method to measure the anterior chamber depth that requires only a Haag-Streit 900 slit lamp. Viewing the anterior chamber at 45 degrees and matching the height of the corneal slit beam to the depth of the anterior chamber enables the observer to calculate the anterior chamber depth by multiplying the measured slit height by 1.4 or, more accurately, by use of the table provided. The accuracy over the range of clinically encountered depths of the anterior changer is +/- 0.2 mm relative to standard pachometry.


The effect of vocal fold augmentation on cough symptoms in the presence of glottic insufficiency.
To determine the effect of injection augmentation of the vocal folds on chronic cough symptoms in patients with glottic insufficiency. Medical records from 146 consecutive patients who underwent vocal fold injection augmentation by a fellowship-trained laryngologist between 2013 and 2015 were reviewed. Twenty-three patients (12 male) met inclusion criteria of a vocal fold augmentation injection, cough symptoms lasting more than 8 weeks, and glottic insufficiency as determined by shortened closed phase on stroboscopy. Exclusion criteria included lack of cough complaints, diagnosis of vocal fold immobility, previous history of vocal fold augmentation, and incomplete data sets. Data collected included age, gender, pre- and 1-month postinjection Cough Severity Index (CSI) scores, location of injection (unilateral or bilateral), and patient statement of percent change in symptoms that was recorded at 1-month postinjection visit. Paired t test indicated a significant decrease in CSI scores from pre- (m = 18.5) to 1-month postinjection (m = 12.1) (P = 0.004). Eighteen patients (78.2%) reported a 50% or greater improvement in cough symptoms at the 1-month postinjection visit. Injection augmentation of the vocal folds in the presence of glottic insufficiency appears to improve cough symptoms, as was reported by CSI in patients who are refractory to other medical and behavioral treatments. 4. Laryngoscope, 128:1316-1319, 2018.


Gonadal steroid-mediated alteration of luteinizing hormone secretion by anterior pituitary cells of young turkeys.
The magnitude of luteinizing hormone (LH) release during a 3-hr test incubation was diminished (P less than 0.05) when anterior pituitary cells from young turkeys were cultured for 24 to 120 hr. This trend was evident with basal LH release and with LH release induced by luteinizing hormone-releasing hormone (LH-RH) or hypothalamic extract. Anterior pituitary cells were cultured with various concentrations (10(-14) to 10(-6) M) of estradiol (E2), progesterone (P4), or testosterone (T) for 24 hr and then exposed to LH-RH or control medium for 3 hr, still in the presence of steroids. Basal LH release was potentiated (P less than 0.05) when cells were cultured with 10(-8) or 10(-6) M T, but not with E2 or P4. When cells were cultured with E2, LH release in the presence of 10(-8) M LH-RH was enhanced (P less than 0.05) in a dose-dependent fashion. LH-RH mediated LH release was also enhanced (P less than 0.05) when cells were cultured with 10(-8) M P4 or 10(-6) M T. Gonadal steroids can act directly on the anterior pituitary of the young domestic turkey to modulate LH release, with T enhancing basal LH release and E2 potentiating LH-RH-mediated LH release.


Detection of Burkholderia pseudomallei toxin-mediated inhibition of protein synthesis using a Caenorhabditis elegans ugt-29 biosensor.
Toxins are believed to play a crucial role in Burkholderia pseudomallei pathogenicity, however to date, only a few have been identified. The discovery of additional toxic molecules is limited by the lack of a sensitive indicator of B. pseudomallei toxicity. Previously, from a whole genome transcriptome analysis of B. pseudomallei-infected Caenorhabditis elegans, we noted significant overexpression of a number of worm genes encoding detoxification enzymes, indicating the host's attempt to clear bacterial toxic molecules. One of these genes, ugt-29, a family member of UDP-glucuronosyltransferases, was the most robustly induced phase II detoxification gene. In this study, we show that strong induction of ugt-29 is restricted to infections by the most virulent species among the pathogens tested. We also noted that ugt-29 is activated upon disruption of host protein synthesis. Hence, we propose that UGT-29 could be a promising biosensor to detect B. pseudomallei toxins that compromise host protein synthesis. The identification of bactobolin, a polyketide-peptide hybrid molecule, as a toxic molecule of B. pseudomallei further verifies the utilization of this surveillance system to search for bacterial toxins. Hence, a ugt-29 based reporter should be useful in screening for other molecules that inhibit host protein synthesis.


Voluntary consumption of alcohol by baboons. Effects of flavor, concentration and temperature of solution.
Nonrestrained, group-housed baboons drank the greatest amounts of alcohol when it was presented as a 10% to 20% solution in cold fruit juice.


Psychotherapy with phobic patients: the marriage relationship as the source of symptoms and focus of treatment.
Four patients demonstrating phobic symptoms occurring in the context of maladaptive marriages are presented. Thorough historical data collection is stressed. Similarities in family backgrounds and personality styles emerge in these cases and are discussed in relation to genesis of symptoms within the marital relationships. A psychotherapeutic approach is described and results of treatment examined.


[Prevention of infections related to health care in primary care. Lessons from the pandemic].
The health system failed to guarantee the safety of both professionals and citizens who came to the centers at the beginning of the pandemic. The lack of materials and guidelines for the prevention of infections caused in Spain the worst catastrophe in the history of patient safety and occupational health in healthcare. It also happened in other countries but Spain had the highest rates of infected health workers in the world. It was a largely avoidable event. We review what measures have been taken to prevent infections in primary care centers, such as hand hygiene, masks and personal protection material or the maintenance of social distance, among others. We update the recommendations and raise the perspectives in a situation that requires flexibility and adaptability to maintain quality and safe care.


Cost-Effectiveness of Tenofovir Alafenamide for Treatment of Chronic Hepatitis B in Canada.
Tenofovir alafenamide (TAF) has been approved for treating chronic hepatitis B (CHB) due to a proposed better safety profile in comparison with current therapies. We evaluated the cost effectiveness of TAF and other available treatment options for hepatitis B envelope antigen (HBeAg)-positive and HBeAg-negative CHB patients from a Canadian provincial Ministry of Health perspective. A state-transition model based on the published literature was developed to compare treatment strategies involving entecavir (ETV), tenofovir disoproxil fumarate (TDF), and TAF. It adopted a lifetime time horizon. Outcomes measured were predicted number of liver-related deaths, costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs). For HBeAg-positive patients, TAF followed by ETV generated an additional 0.16 QALYs/person at an additional cost of Can$14,836.18 with an ICER of Can$94,142.71/QALY compared with TDF followed by ETV. Of the iterations, 28.7% showed that it is the optimal strategy with a Can$50,000 willingness-to-pay threshold. For HBeAg-negative patients, ETV followed by TAF would prevent an additional 13 liver-related deaths per 1000 CHB patients compared with TDF, followed by ETV. It generated an additional 0.13 QALYs/person at an additional cost of Can$59,776.53 with an ICER of Can$461,162.21/QALY compared with TDF, followed by ETV. TAF-containing strategies are unlikely to be a rational choice in either case. The results were sensitive to the HBeAg seroconversion rates and viral suppression rates of the treatments. Our analysis suggests that TAF is not cost effective at its current cost. A 33.4% reduction in price would be required to make it cost effective for HBeAg-positive patients with a Can$50,000 willingness-to-pay threshold.


Thrombolytic therapy in older patients.
We compared outcomes following thrombolytic therapy and primary angioplasty with no reperfusion therapy in a population-based cohort of older patients presenting with acute myocardial infarction (AMI) and indications for acute reperfusion. Evidence supporting the efficacy of acute reperfusion (thrombolytic therapy or primary angioplasty) in the elderly with suspected AMI is not as strong as it is in younger groups. From a national cohort of Medicare beneficiaries with AMI, we identified 37,983 patients age 65 or older who presented within 12 h of symptom onset with ST elevation or left bundle branch block. A total of 14,341 (37.8%) received thrombolytic therapy and 1,599 (4.2%) underwent primary angioplasty within 6 h of hospital arrival. After adjustment for demographic, clinical, hospital and physician factors, and co-interventions, thrombolytic therapy was not associated with a better 30-day survival (odds ratio [OR] 1.01; 95% confidence interval [CI]: 0.94 to 1.09) compared with no therapy, whereas primary angioplasty was (OR 0.79; 95% CI: 0.66 to 0.94). At one year, both thrombolytic therapy (OR 0.84; 95% CI: 0.79 to 0.89) and primary angioplasty (OR 0.71; 95% CI: 0.61 to 0.83) were associated with a survival benefit. In this national sample of older patients, those who received thrombolytic therapy or primary angioplasty had lower mortality at one year compared with those who did not receive a reperfusion strategy. However, only primary angioplasty was associated with better survival at 30 days. Our findings should heighten interest in further investigating the best approach to the treatment of older patients with suspected AMI and ST segment elevation or left bundle branch block.


An unusual role of the vinculum after complete laceration of the flexor tendons.
Two cases are described with full flexion of the proximal interphalangeal joint produced by an intact short vinculum after complete laceration of both superficialis and profundus tendons. To establish the clinical diagnosis of complete flexor digitorum superficialis division, the necessity of examining the flexion strength of an injured finger is emphasized.


[Inhibitory effect of pyrogallic acid on Microcystis aeruginosa and the model analysis].
To explore the effective agent to inhibit the growth of water-bloom algae and establish corresponding forecast model based on the inhibitory effect. The inhibitory effect of pyrogallic acid at different concentrations on Microcystis aeruginosa was studied in the indoor control conditions and the mathematical model of algal growth inhibition was established based on the traditional Logistic model. (1) Pyrogallic acid has strong power to inhibit the growth of Microcystis aeruginosa, the EC50 of the fifth day was 0.658 mg/L. (2) The law of algal density changing with time can be effectively analysed and forecasted by this model, and based on this model, the half effective concentration (EC50) and the minimal inhibitory concentration (MIC) at different time point also can be projected. This experiment indicated that pyrogallic acid had some potential to be developed into biological algicide agent, and the mathematical model has some reference application value for using allelochemicals to inhibit the growth of water-bloom algae.


Effectiveness of home hospice care: a nationwide prospective observational study.
Many assert the need for home hospice care. However, limited research has shown its effectiveness. The authors of this study thus evaluated the effectiveness of a home hospice care pilot project regarding (1) early enrollment in hospice care, (2) efficient use of inpatient hospice resources, and (3) enabling terminally ill patients to stay at their preferred place of care. The authors conducted a nationwide prospective observational study. Patients were divided into home hospice care users (ever-users, n = 902) and inpatient-only hospice care users (never-users, n = 8210). Information about hospice service utilization was collected from a web-based registry system. Patients were registered if they started to receive the hospice service after providing written informed consent during the pilot project from March 2016-July 2017. Most ever-users preferred to stay at home (84.0%), while never-users preferred hospital admission (66.9%). Most ever-users were enrolled in hospice by home care (78.9%) and used both home and inpatient care (72.4%). The overall duration of hospice care was significantly longer among ever-users than never-users (median 39 vs. 15 days, respectively; mean ± SD 59.6 ± 62.8 vs. 24.8 ± 32.1, respectively; p < .001). Participation in the pilot program improved bed utilization (p = .025) and turnover rate (p < .001) of inpatient hospice service. Home hospice care enabled early enrollment in hospice services and provided a valid option to patients who wished to stay at home. Policy efforts to facilitate home hospice care are needed.


Moving beyond a figurative psychedelic literacy: Metaphors of psychiatric symptoms in ayahuasca narratives.
Metaphors, analogies, and similes commonly appear in narratives of drinking the potent psychedelic "ayahuasca", presenting an intriguing transcultural pattern. Based upon survey and field research at an ayahuasca healing center in Pucallpa, Peru, the article investigates conceptual metaphors in narratives of ayahuasca experiences made by the visiting international guests. Bodily metaphors and visionary analogies frequently appear in narrative plots where they can express the reappraisal, overcoming, and sometimes emboldening of symptoms diagnosed by psychiatry. Moving beyond the literal-figurative divide, the article explores the intrinsic "metaphoricity" of psychedelic experiences and advocates for a literacy of conceptual metaphors regarding both clinical and non-clinical psychedelic narratives. Developing this literacy can broaden approaches in psychedelic psychiatry that analyze and treat syndromes and disorders, while also being applicable to social science and humanities research that examine psychoactive drug use beyond medical frameworks.


Stimulus intensity modulation and alcohol consumption.
In a study of men alcoholics, cortical average evoked response proved to be a good indicator of subsequent alcohol acquisition and consumption behavior in the laboratory.


[Clinical observations on effects on prognostic factor treating hepatitis B-related cirrhosis with purification purgation dispersion tonicity].
With prognostic factors as assessment standards, the effects of combination of TCM(purification purgation dispersion tonicity) and western medicine treating hepatitis B-related cirrhosis and its complications were assessed. In this study, study group and control group were divided, the number of each group was 30. In order to keep balance between the two groups, matching control design was adopted with Wang's 8 prognostic factors as matching conditions. In study group, except Hb, TBIL, ALB and PT had statistic difference, and the complications of cirrhosis such as ascites, HEP and UGH were treated with significant effects. Between study group and control group, in all of prognostic factors only TBIL had statistical diffirence. It suggested the effects were significant treating hepatitis B-related cirrhosis and its complications with combination of TCM(purification purgation dispersion tonicity) and western medicine. It also suggested that TCM therapy combining purification, purgation, dispersion and tonicity had significant effects on reducing jaundice.


Protective effects of Terminalia arjuna against Doxorubicin-induced cardiotoxicity.
Terminalia arjuna has been marked as a potential cardioprotective agent since vedic period. The present study was aimed to investigate the effects of butanolic fraction of Terminalia arjuna bark (TA-05) on Doxorubicin (Dox)-induced cardiotoxicity. Male wistar rats were used as in vivo model for the study. TA-05 was administered orally to Wistar rats at different doses (0.42 mg/kg, 0.85 mg/kg, 1.7 mg/kg, 3.4 mg/kg and 6.8 mg/kg) for 6 days/week for 4 weeks. Thereafter, all the animals except saline and TA-05-treated controls were administered 20 mg/kg Dox intraperitonially. There was a significant decrease in myocardial superoxide dismutase (38.94%) and reduced glutathione (23.84%) in animals treated with Dox. Concurrently marked increase in serum creatine kinase-MB (CKMB) activity (48.11%) as well as increase in extent of lipid peroxidation (2.55-fold) was reported. Co-treatment of TA-05 and Dox resulted in an increase in the cardiac antioxidant enzymes, decrease in serum CKMB levels and reduction in lipid peroxidation as compared to Dox-treated animals. Electron microscopic studies in Dox-treated animals revealed mitochondrial swelling, Z-band disarray, focal dilatation of smooth endoplasmic reticulum (SER) and lipid inclusions, whereas the concurrent administration of TA-05 led to a lesser degree of Dox-induced histological alterations. These findings suggest that butanolic fraction of Terminalia arjuna bark has protective effects against Dox-induced cardiotoxicity and may have potential as a cardioprotective agent.


Effect of hydration on the strain gradients in dental hard tissues after heat and cold application.
This study was aimed to investigate the thermal strain gradients on dental hard tissues to localized heat and cold applications, applied to assess the vitality of pulp. The role of hydration on the thermal strain distribution within the enamel, dentin, and dentino-enamel junction (DEJ) was examined by using a digital moiré interferometry. Extracted bovine incisors were prepared, and high-frequency diffraction gratings were replicated on one surface. Heat (120°C-140°C) and cold (-50°C) stimuli were applied on the external surface, and the strain patterns were recorded and analyzed for the first 3 seconds. The specimens were tested under fully hydrated and partially dehydrated conditions (72 hours at 24°C, 60% relative humidity). Distinct thermal strain gradient was observed in the enamel, dentin, and DEJ after the application of heat and cold stimuli. Application of both heat and cold resulted in significantly higher strains in the partially dehydrated teeth than in the fully hydrated teeth (P < .05). There was only a marginal increase in strains at the location of application of stimuli in hydrated teeth. The DEJ in both the fully hydrated and partially dehydrated teeth showed the highest strains. There was a marked difference in the thermal strain gradients within dental hard tissues after the application of heat/cold stimuli, depending on the level of tissue hydration. The findings from this study highlighted the role of free water and structural characteristics of enamel, dentin, and DEJ in dissipating the thermal strains in the tooth.


Investigation of pore water and soil extraction tests for characterizing the fate of poorly soluble metal-oxide nanoparticles.
Here we compared the efficiency of Cu extraction (dissolved + particulate) from two soils dosed with CuO nanoparticles (NPs) at 50 or 250 mg kg-1 by pore water collection, and single- and multi-step soil extraction tests. Pore water collection recovered low levels of Cu (<0.18%, regardless of soil type or Cu dose). Single soil extraction by either CaCl2 or DI water led to higher Cu recovery than pore water collection, but still <3% of total dose. These methods were useful for assessing the labile Cu ions pool. This fraction is controlled by Cu2+ dissolved from CuO NPs and it varies with time and soil type. Particulate Cu was poorly retrieved (<0.7%) by pore water extraction and by single-step soil extraction using CaCl2 solution or water. Multi-step extraction including dispersing and metal-chelating agents allowed for simultaneous characterization of dissolved Cu (total ionic Cu2+, 24-49% of dosed Cu), extractable CuO NPs (reversibly attached, 15-26% of dosed Cu), and non-extractable CuO NPs (irreversibly attached, 36-50% of dosed Cu), and it could describe the aging of NPs along 30 d. This method extracted a significantly higher concentration of Cu than pore water collection and was less sensitive to method parameters (e.g. filtration). This multi-step method can reduce pore water extraction-related factors that may confound the interpretation of environmental exposure data in NPs studies, and describe upper limits of both exchangeable Cu2+ and dispersible CuO NPs in soil that can potentially become bioavailable to plants and organisms and thus provide a sounder basis for risks evaluations.


Bilateral fungal epididymo-orchitis with abscess.
We present a unique case of bilateral fungal epididymo-orchitis with abscess formation due to Torulopsis glabrata in a nonimmunosuppressed patient with a neurogenic bladder. This case highlights the risk factors for fungal infections of the urinary tract and the difficulty with their management.


Clinical epidemiology of atrial fibrillation and related cerebrovascular events in the United States.
Atrial fibrillation (AF) is an important, independent risk factor for stroke and is estimated to cause a 5-fold increase in ischemic stroke risk. The aim of this article is to describe the changing epidemiology of AF in the United States and to assess the implications for stroke prevention and treatment. AF prevalence is increasing in the general population. This is likely due to the aging of the population, the improvements in coronary care and the rising prevalence of AF risk factors such as diabetes. Risk factors such as rheumatic heart disease and hypertension have decreased in prevalence over the past few decades. However, novel risk factors such as obesity and possibly the metabolic syndrome have been identified and these have the potential to further increase AF prevalence. The utilization of warfarin has improved and this is reflected in falling ischemic stroke rates in the AF population. There is evidence for an increased incidence of anticoagulant associated intraparenchymal hemorrhages during the 1990s. Although the decline in stroke rates in AF is laudable, the rising prevalence of AF, the changing profile of risk factors, and the recent plateauing of warfarin use indicate that stroke in AF patients will continue to be a significant public health problem.


Successful conservative management of thrombocytopenia in adult hemophiliacs.
Hematologic abnormalities, including thrombocytopenia, have been reported in persons with acquired immune deficiency syndrome and in hemophiliacs. Seven of 92 adult hemophiliacs followed in a comprehensive hemophilia center developed mild to moderately severe thrombocytopenia in 1983. All had benign courses. None required therapy for thrombocytopenia, although several had increased cutaneous bleeding. Infection with human immunodeficiency virus may be important in the pathogenesis of these patients' thrombocytopenia as it has been in that of homosexual men.


Increasing but levelling out risk of revision due to infection after total hip arthroplasty: a study on 108,854 primary THAs in the Norwegian Arthroplasty Register from 2005 to 2019.
Background and purpose - Focus on prevention, surveillance, and treatment of infection after total hip arthroplasty (THA) in the last decade has resulted in new knowledge and guidelines. Previous publications have suggested an increased incidence of surgical revisions due to infection after THA. We assessed whether there have been changes in the risk of revision due to deep infection after primary THAs reported to the Norwegian Arthroplasty Register (NAR) over the period 2005-2019.Patients and methods - Primary THAs reported to the NAR from January 1, 2005 to December 31, 2019 were included. Adjusted Cox regression analyses with the first revision due to deep infection after primary THA were performed. We investigated changes in the risk of revision as a function of time of primary THA. Time was stratified into 5-year periods. We studied the whole population of THAs, and the subgroups: all-cemented, all-uncemented, reverse hybrid (cemented cup), and hybrid THAs (cemented stem). In addition, we investigated factors that were associated with the risk of revision, and changes in the time span from primary THA to revision.Results - Of the 108,854 primary THAs that met the inclusion criteria, 1,365 (1.3%) were revised due to deep infection. The risk of revision due to infection, at any time after primary surgery, increased through the period studied. Compared with THAs implanted in 2005-2009, the relative risk of revision due to infection was 1.4 (95% CI 1.2-1.7) for 2010-2014, and 1.6 (1.1-1.9) for 2015-2019. We found an increased risk for all types of implant fixation. Compared to 2005-2009, for all THAs, the risk of revision due to infection 0-30 days postoperatively was 2.2 (1.8-2.8) for 2010-2014 and 2.3 (1.8-2.9) for 2015-2019, 31-90 days postoperatively 1.0 (0.7-1.6) for 2010-2014 and 1.6 (1.0-2.5) for 2015-2019, and finally 91 days-1 year postoperatively 1.1 (0.7-1.8) for 2010-2014 and 1.6 (1.0-2.6) for 2015-2019. From 1 to 5 years postoperatively, the risk of revision due to infection was similar to 2005-2009 for both the subsequent time periodsInterpretation - The risk of revision due to deep infection after THA increased throughout the period 2005-2019, but appears to have levelled out after 2010. The increase was mainly due to an increased risk of early revisions, and may partly have been caused by a change of practice rather than a change in the incidence of infection.


Seasonal pattern and energetics of short daily torpor in the Djungarian hamster, Phodopus sungorus.
In Phodopus sungorus spontaneous shallow daily torpor occurred only during winter. Frequency of torpor was not affected by low ambient temperature but the seasonal cueing seems primarily dependent on photoperiodic control. Maximum torpor frequency was found in January with 30% of all hamsters living inside or outside being torpid at a time. It is calculated that torpor will reduce long term energy requirements of Phodopus by only 5%. Therefore it is concluded that torpor is not primarily aimed to reduce energy requirements but to guarantee survival of a fraction of a population during short periods of extreme cold load or inaccessability of food.


Relevance of oestrone presentation to the specificity of the elicited antisera, as revealed by affinity separation.
Polyclonal antisera raised against two different azobenzoyl-oestrone derivatives were analysed to investigate both the latency/intensity relationship of the immune response and the influence of antigen presentation on the specificity of the antisera elicited. Elongation of the azo-bridge of the hapten ([p(carboxyphenyl)-azo]-1,3,5[10]- oestratrien-3 ol-17 one) with a short aliphatic chain (4-amino-n-butyric acid) resulted in a marginal increase in the antibody yield, without affecting the time required to attain the maximum titre. The increased flexibility and mobility of the extended azo-bridge was shown to result in the appearance of antisera which cross-reacted with oestrogens with D ring structures different to that of oestrone. Antiserum fractionation by affinity chromatography through a stationary phase exposing the carrier protein determinants, as modified by the addition of the coupling bridge and the phenol ring, resulted in a reduction in its specificity. These findings are discussed with regard to the phenomena underlying the specificity of a polyclonal antiserum.


Fluoroscopy time analysis of a prospective, multi-centre study comparing robotic- and fluoroscopic-guided placement of percutaneous pedicle screw instrumentation for short segment minimally invasive lumbar fusion surgery.
As minimally invasive spine surgery becomes more widespread, concerns regarding radiation exposure to surgeons and patients alike have become a growing concern. Robotic guidance has been developed as a way to increase the accuracy of instrumentation while decreasing radiation burden. A retrospective analysis of a large, multi-centre, prospective study comparing robotic-guided (RG) to fluoroscopic-guided (FG) (Multi-centre, Partially Randomized, Controlled Trial of MIS Robotic vs. Freehand in Short Adult Degenerative Spinal Fusion Surgeries) was performed to evaluate for differences in radiation exposure between study groups. RG was associated with 78.3% (p < 0.001) and 79.8% (p < 0.001) reduction in total and per screw fluoroscopy times, respectively, as compared to FG. RG was also associated with a 50.8% (p < 0.001) reduction in total operative fluoroscopy time. RG was associated with significantly lower fluoroscopy times compared to FG. This suggests that utilization of robotic navigation systems may result in decreased operative radiation exposure, which is a growing concern for surgeons performing minimally invasive spine surgery.


Quantifying absolute neutralization titers against SARS-CoV-2 by a standardized virus neutralization assay allows for cross-cohort comparisons of COVID-19 sera.
The global COVID-19 pandemic has mobilized efforts to develop vaccines and antibody-based therapeutics, including convalescent plasma therapy, that inhibit viral entry by inducing or transferring neutralizing antibodies (nAbs) against the SARS-CoV-2 spike glycoprotein (CoV2-S). However, rigorous efficacy testing requires extensive screening with live virus under onerous BSL3 conditions which limits high throughput screening of patient and vaccine sera. Myriad BSL-2 compatible surrogate virus neutralization assays (VNAs) have been developed to overcome this barrier. Yet, there is marked variability between VNAs and how their results are presented, making inter-group comparisons difficult. To address these limitations, we developed a standardized VNA using VSVΔG-based CoV-2-S pseudotyped particles (CoV2pp) that can be robustly produced at scale and generate accurate neutralizing titers within 18 hours post-infection. Our standardized CoV2pp VNA showed a strong positive correlation with CoV2-S ELISA and live virus neutralizations in confirmed convalescent patient sera. Three independent groups subsequently validated our standardized CoV2pp VNA (n>120). Our data show that absolute (abs) IC50, IC80, and IC90 values can be legitimately compared across diverse cohorts, highlight the substantial but consistent variability in neutralization potency across these cohorts, and support the use of absIC80 as a more meaningful metric for assessing the neutralization potency of vaccine or convalescent sera. Lastly, we used our CoV2pp in a screen to identify ultra-permissive 293T clones that stably express ACE2 or ACE2+TMPRSS2. When used in combination with our CoV2pp, we can now produce CoV2pp sufficient for 150,000 standardized VNA/week.


Exploring factors that influence the behavioural intention of medical students to use 3D gastroscopic model to learn how to operate gastroscope using UTAUT Model.
The application of virtual reality (VR) in gastroscopic operation teaching can be safe and effective, but the advantages can be realized only when students accept and use it. This study aims to identify the factors influencing Chinese clinical medical postgraduates on their intention to use the 3D gastroscopic model constructed based on VR technology using Unified Theory of Acceptance and Use of Technology (UTAUT) model. Students' demographic factors are also taken into consideration. All methods were carried out in accordance with relevant guidelines. Data were collected from clinical medical postgraduates students in China using stratified sampling. A total of 292 questionnaires including valid responses were used in this study. Data were processed using Amos 24.0 and SPSS 26.0 software and the statistical analysis technique was based on structural equation modeling (SEM). The results showed that different from the mediator of home location and year of clinical learning, mediator of gender, university kind and graduate degree did not affect the behavioral intention. In addition, performance expectancy, facilitating condition, and social influence directly and indirectly have effect on behavioral intention. Also, the significance between social influence and performance expectancy, social influence and effort expectancy were verified. This study manifested that the proposed framework based on the UTAUT had explanatory power to identify the factors influencing the students' behavioral intention to use the 3D gastroscopic model constructed based on VR technology. Whereas, an important variable of effort expectancy in the frame of the SEM were not certified, thereby indicating that particular attention should be paid to this variable by universities and teachers before applying 3D gastroscopic model constructed based on VR technology in teaching. Added preparatory work is required such as explaining the basic knowledge of the operating steps of VR model and make students adequately understand its accessibility, which can probably improve the intentions of them to use it. The positive effects of social influence on performance expectancy and effort expectancy we proposed was also verified in this study, which provided a direction for future research.


Financial implications of ventilator care.
Mechanical ventilation is in the forefront of modern technologic advances. These advances can be life saving for some, death prolonging for others. As difficult medical, ethical, and economic issues are raised in relation to life-sustaining treatments, it is important to have as complete a data base as possible concerning costs and outcomes of mechanical ventilation, so that physicians, patients, families, and society as a whole can make appropriate decisions regarding its use.


Distance matters: The association of proximity to syringe services programs with sharing of syringes and injecting equipment - 17 U.S. cities, 2015.
Syringe services programs (SSPs) have effectively limited the spread of HIV and hepatitis C (HCV) among people who inject drugs (PWID). Access to SSPs has been shown to reduce injection risk behaviors but the relationship between distance to an SSP and likelihood of sharing injection equipment is not well known. We analyzed a sample of 8,392 PWID from 17 U.S. cities recruited through the National HIV Behavioral Surveillance (NHBS) system in 2015. Adjusted prevalence ratios (aPR) and 95% confidence intervals (CI) were estimated from log-linked Poisson regression to explore associations between injecting equipment sharing in the past 12 months and distance to the nearest SSP. Regardless of SSP use, respondents who lived in zip codes further than the city-specific mean distance to nearest SSP were more likely to report sharing behavior. Among PWID who had not reported using an SSP in the previous 12 months, distributive sharing (aPR=1.13 95% CI=1.05, 1.21), receptive sharing (aPR=1.15, 95% CI=1.06, 1.24), and injection equipment sharing (aPR=1.08, 95% CI=1.03, 1.13) were more prevalent among residents who resided further than the average distance to the nearest SSP. Greater distance to an SSP was associated with increased sharing behaviors. Improved access to an SSP and subsequent decreases in sharing behaviors could reduce transmission of HIV and HCV among PWID. Accessibility should be taken into account when planning provision of SSPs.


The amino acid sequence of human pancreatic ribonuclease.
The primary structure of human (Homo sapiens) pancreatic ribonuclease has been determined by automatic sequencing of the native protein and by analysis of peptides obtained by cleavage with proteolytic enzymes, cyanogen bromide, and hydroxylamine. The following sequence was deduced: (sequence in text). Human pancreatic ribonuclease differs at 37 positions from bovine pancreatic ribonuclease. In addition the human enzyme has three more residues at the C-terminus. About half of the enzyme molecules contain carbohydrate attached to the sequence Asn-Met-Thr (34-36). Two other Asn-X-Ser/Thr sequences are carbohydrate free. Human pancreatic ribonuclease contains many positively charged residues, especially near the N-terminus, while negatively charged residues are more concentrated near the C-terminus.


The importance of cerebrospinal fluid lactate in the evaluation of congenital lactic acidosis.
In 27 of 28 children with congenital lactic acidosis, cerebrospinal fluid lactate was higher than venous blood lactate. The mean +/- SEM difference between these variables was 2.4 +/- 0.3 mmol/L (P =.0001). Girls or patients with pyruvate dehydrogenase deficiency had higher cerebrospinal fluid lactate concentrations than boys or patients with respiratory chain defects or mitochondrial DNA mutations.


Audiogenic kindling in Wistar and WAG/Rij rats: kindling-prone and kindling-resistant subpopulations.
Audiogenic kindling (AK) is a model of naturally occurring epileptogenesis triggered by repeated sound stimulation of rats genetically prone to audiogenic seizures. It is accepted that limbic seizure networks underlie progressive changes in behavioral seizure pattern during AK. The present study investigated AK progression in rats susceptible and unsusceptible to absence seizures. Progression of AK as indicated by an appearance and intensification of limbic clonus was examined in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats with genetic absence epilepsy and in Wistar rats. Subpopulations of kindling-prone and kindling-resistant rats were found in both Wistar and WAG/Rij strains. Despite identical seizure responses to the first sound stimulation, AK progression dramatically differed between the two subpopulations. AK-prone rats exhibited rapid kindling development up to maximal stage-5 severity. In AK-resistant rats, limbic clonus did not appear after 30 stimulations or if it appeared, it did not progress beyond stage 2. The proportions of AK-prone and AK-resistant animals within Wistar and WAG/Rij strains were similar. Comparison of Wistar and WAG/Rij rats within the kindling-prone and kindling-resistant groups did not reveal a significant strain effect on AK progression. However, within the WAG/Rij strain, a significantly higher incidence of absence seizures was found in AK-resistant rats compared to AK-prone rats. The present study demonstrates that sensitivity to sound-induced epileptogenesis differs dramatically within Wistar and WAG/Rij strains, whereas genetic susceptibility to absence seizures does not change AK progression significantly. It is supposed that an increased incidence of nonconvulsive seizures and resistance to kindling result from a common seizure modulating mechanism.


The addition of biochar and nitrogen alters the microbial community and their cooccurrence network by affecting soil properties.
Biochar plays an important role in reducing the harmful environmental effects of inorganic nitrogen (N) fertilizers on agroecosystems, but the the impact mechanisms of biochar combined with N fertilizers on soil microorganisms are not clear enough. In this study, high-throughput sequencing was used to study the influences of three N fertilizer levels (0 (N0), 90 (N90) and 120 (N120) kg ha-1) and two biochar levels (0 (B0) and 20 (B20) t ha-1) on the soil microbial community and symbiotic network among microbial taxa in wheat fields. Compared to the control (B0N0), N fertilizer alone or combined with biochar significantly increased soil total N, available N, and organic matter in topsoil (0-20 cm), and the same results were found only in B20N120 treatment in subsoil (20-40 cm). In addition, bacterial and fungal diversity in topsoil were significantly increased and decreased by all N and biochar treatments, respectively. Moreover, soil bacterial and fungal community compositions also were also changed by N and biochar. Furthermore, biochar weakened the competition and cooperation among microorganisms in topsoil and subsoil, and the keystone species of networks were also changed by biochar. Redundancy analysis showed that soil total N, available N, available P, available K and pH were the main environmental factors driving the changes in bacterial and fungal community structures. These data indicated that the addition of N fertilizer and biochar could improve soil fertility by maintaining the stability of microbial community structures, which can provide reasonable guidance for the sustainable development of agriculture, such as maintaining dryland production.


Collagen content, histology, and tensile strength: determinants of wound repair in various gastric stapling devices in a canine gastric partition model.
Various stapling devices have been applied to create the small gastric pouch necessary for effective weight loss in morbid obesity, but it is unclear as to which staple line arrangement provides the most reliable gastric wound healing. Five variants of staple lines (Groups I-V) were used to create a gastric partition in 47 adult mongrel dogs (20-30 kg). Staple-line arrangements were as follows: Group I (n = 10)--two superimposed double rows (TA-90), Group II (n = 10)--prototype staple line of four rows 2.03 mm apart, Group III (n = 12)--two double rows of staples 6.5 mm apart, Group IV (n = 10)--prototype staple line of two double rows of staples 0.64 mm apart, and Group V (n = 5)--a single double-row staple line (TA-90). Staple lines were examined at 2, 4, 8, and 13-16 weeks for evidence of healing, histology, tensile strength, and collagen (hydroxyproline) content. Significant differences in staple-line disruption rates were found between all groups (chi 2, P less than 0.01). The prototype four-row staple line (Group II) had the most significant parameters of wound repair determined by biochemical evidence of wound healing and enhanced tensile strength. Staple-line arrangement appears to be an important determinant of gastric wound healing and may influence the rate of postoperative gastric partition disruption.


[Pancreatic secretory trypsin inhibitor gene N34S mutation in patients with idiopathic chronic pancreatitis].
To determine the frequency and prognostic significance of mutation N34S in the development of CP in a mixed Russian population. The study included 83 patients with idiopathic CP and 103 healthy individuals. The diagnosis of CP was based on clinical and instrumental data in accordance with the criteria of M-ANNHEIM. Everyone involved in this study using PCR followed by restriction analysis performed the N34S mutation analysis in the gene for the ICU. N34S mutation was detected in 12 patients with CP and in 3 of the control group, which accounted for 14.6 and 2.9% respectively; p<0,05. The odds ratio (OR) of idiopathic CP in the presence of mutation N34S was 4.62 (95% confidence interval (CI): 1,21-18,37). The difference in frequency of homozygotes the mutant allele was statistically significant: 10.97 and 0.97% in the main and control groups, respectively; p<0,05. The presence of mutations did not affect the frequency and severity of functional disorders of the pancreas, but the mutation N34S was statistically significantly more common in patients with calcifying pancreatitis (p<0,01) and the presence of pseudocysts (p<0,05). OR the development of calcification in patients with the presence of N345 was 13.44 (95% CI: 6,29-23,78). These data suggest that the mutation N34S plays a significant role in the development of CP in the Russian population and can detect more than 10% of cases of idiopathic CP.


Ventricular aneurysms and other lesions produced by the struts of bioprosthetic valves implanted in sheep.
Damage to the posterolateral wall of the left ventricle was found in eight of approximately 700 sheep undergoing mitral valvular replacement as part of animal model studies of bioprosthetic valves. The damage consisted of left ventricular aneurysms in five animals, subacute rupture of the left ventricle in one, acute left ventricular laceration in one, and endocardial scarring in one. Six of the eight bioprostheses were bovine pericardial valves, including five low-profile valves and one standard valve; of the two porcine bioprostheses, one was intentionally oversized and the other was a low-profile supra-annular valve. In each of these animals the damage appeared to have been caused by contact between the most posterior strut of the bioprosthesis and the left ventricular wall.


Gaps in community workforce putting pressure on parents.
THE WELLCHILD charity has called for workforce and training to be reviewed as it celebrates its tenth anniversary.


"That's probably what my mama's lungs look like": how adolescent children react to pictorial warnings on their parents' cigarette packs.
Pictorial cigarette pack warnings discourage smoking, but most evidence comes from studies of adults. Our qualitative study explored adolescents' reactions to pictorial warnings on their parents' cigarette packs. We interviewed 24 adolescents whose parents received pictorial warnings on their cigarette packs as part of a randomized clinical trial. We conducted a thematic content analysis of the interview transcripts. Pictorial cigarette pack warnings led adolescents to imagine the depicted health effects happening to their parents, which elicited negative emotions. The warnings inspired adolescents to initiate conversations with their parents and others about quitting smoking. Adolescents believed the warnings would help smokers quit and prevent youth from starting smoking. Some current smokers said the warnings made them consider quitting. Conversations about the pictorial warnings may amplify their effectiveness for smokers, their adolescent children, and friends of the adolescent children. Cigarette pack warnings may reach a broad audience that includes adolescent children of smokers.


In situ hybridization with complementary synthetic oligonucleotide and immunocytochemistry: a combination of methods to study transcription and secretion of oxytocin by hypothalamic neurons.
We have constructed an icosameric, anti-sense oligodeoxyribonucleotide probe derived from the published sequence of rat oxytocin gene precursor that was used for in situ hybridization, combined with immunostaining, to characterize the biosynthetic and secretory activity of hypothalamic oxytocin neurons. The population of hybridized neurons overlapped with the pattern of oxytocin immunoreactive cells, except for a fraction of these cells which remained unhybridized. A number of hybridized neurons remained unstained. The differential proportion of hybridized and immunostained neurons are interpreted as differences in secretory turnover of endocrine neurons.


Socioeconomic position and the incidence of type 2 diabetes: the ELSA study.
We examined the associations between childhood and adult socioeconomic position (SEP) and incident diabetes in 7,432 individuals aged 50 or older from the English Longitudinal Study of Ageing (ELSA). We identified 174 and 189 cases of incident diabetes, in men and women, respectively, over 5.3 years of follow-up. Cox models were estimated. In women, childhood SEP, education, occupational class, income, wealth, and subjective social status (SSS) were related to incident diabetes. Occupational class, income, and SSS did not remain significantly related to incident diabetes after adjustment for individual sets of covariates (i.e. unhealthy behaviours, obesity, or psychosocial factors). Wealth (HR: 1.65, 95 % CI: 1.05, 2.60, poorest vs. wealthiest tertile) remained significantly related to incident diabetes after adjustment for all covariates, but education (HR: 1.46, 95 % CI: 0.92, 2.33, lowest vs. highest category) and childhood SEP (HR: 1.47, 95 % CI: 0.98, 2.19, lowest vs. highest category) did not. In men, only wealth and SSS were related to incident diabetes. SSS remained significantly related to incident diabetes after adjustment for all covariates (HR: 2.46, 95 % CI: 1.32, 4.68, lowest vs. highest category), but wealth did not (HR: 1.42, 95 % CI: 0.94, 2.15, poorest vs. wealthiest tertile). Additional adjustment for wealth did not greatly affect the association between incident diabetes and SSS in men. Incident diabetes in older women is associated with SEP from all life stages, while in older men only with current SEP. Psychosocial factors (in women), unhealthy behaviours, and obesity partly mediate these associations.


Assay of nicotinamide deamidase activity using high-performance liquid chromatography.
A rapid, simple and reproducible method has been developed for the determination of nicotinamide deamidase activity using high-performance liquid chromatography (HPLC). Nicotinic acid (NA) liberated from nicotinamide (NAA) after a 15-min enzyme reaction was determined directly by HPLC without further separation steps. Both NA, the product, and NAA, the substrate were separated by reversed-phase ion-pair isocratic chromatography and detected at 261 nm. The present method could be applied to the measurement of deamidase activity in crude cell extracts prepared from several bacterial strains. The Michaelis constant of nicotinamide deamidase in Enterobacter agglomerans was 36 microM for NAA. This method is useful for the measurement of nicotinamide deamidase from various sources.


Analysis of wheat gene expression related to the oxidative stress response and signal transduction under short-term osmotic stress.
Water shortage is a major environmental stress that causes the generation of reactive oxygen species (ROS). The increase in ROS production induces molecular responses, which are key factors in determining the level of plant tolerance to stresses, including drought. The aim of this study was to determine the expression levels of genes encoding MAPKs (MAPK3 and MAPK6), antioxidant enzymes (CAT, APX and GPX) and enzymes involved in proline biosynthesis (P5CS and P5CR) in Triticum aestivum L. seedlings in response to short-term drought conditions. A series of wheat intervarietal substitution lines (ISCSLs) obtained by the substitution of single chromosomes from a drought-sensitive cultivar into the genetic background of a drought-tolerant cultivar was used. This source material allowed the chromosomal localization of the genetic elements involved in the response to the analyzed stress factor (drought). The results indicated that the initial plant response to drought stress resulted notably in changes in the expression of MAPK6 and CAT and both the P5CS and P5CR genes. Our results showed that the substitution of chromosomes 3B, 5A, 7B and 7D had the greatest impact on the expression level of all tested genes, which indicates that they contain genetic elements that have a significant function in controlling tolerance to water deficits in the wheat genome.


NST- and SND-subgroup NAC proteins coordinately act to regulate secondary cell wall formation in cotton.
Secondary cell wall (SCW) has a strong impact on plant growth and adaptation to the environments. Previous studies have shown that NAC (NAM, ATAF1/2, and CUC2) transcription factors act as key regulators of SCW biosynthesis. However, the regulatory network triggered by NAC proteins is largely unknown, especially in cotton, a model plant for SCW development studies. Here, we show that several cotton NAC transcription factors are clustered in the same group with Arabidopsis secondary wall NACs (SWNs), including secondary wall-associated NAC domain protein1 (SND1) and NAC secondary wall thickening promoting factor1/2 (NST1/2), so we name these cotton orthologs as SND1s and NST1s. We found that simultaneous silencing of SND1s and NST1s led to severe xylem and phloem developmental defect in cotton stems, however silencing either SND1s or NST1s alone had no visible phenotype. Silencing both SND1s and NST1s but not one subgroup caused decreased expression of a set of SCW-associated genes, while over-expression of cotton SWNs in tobacco leaves resulted in SCW deposition. SWNs could bind the promoter of MYB46 and MYB83, which are highly expressed in SCW-rich tissues of cotton. In total, our data provide evidence that cotton SWNs positively and coordinately regulate SCW formation.


Does Heterogeneity Exist in Treatment Associations With Renin-Angiotensin-System Inhibitors or Beta-blockers According to Phenotype Clusters in Heart Failure with Preserved Ejection Fraction?
We explored the association between use of renin-angiotensin system inhibitors and beta-blockers, with mortality/morbidity in 5 previously identified clusters of patients with heart failure with preserved ejection fraction (HFpEF). We analyzed 20,980 patients with HFpEF from the Swedish HF registry, phenotyped into young-low comorbidity burden (12%), atrial fibrillation-hypertensive (32%), older-atrial fibrillation (24%), obese-diabetic (15%), and a cardiorenal cluster (17%). In Cox proportional hazard models with inverse probability weighting, there was no heterogeneity in the association between renin-angiotensin system inhibitor use and cluster membership for any of the outcomes: cardiovascular (CV) mortality, all-cause mortality, HF hospitalisation, CV hospitalisation, or non-CV hospitalisation. In contrast, we found a statistical interaction between beta-blocker use and cluster membership for all-cause mortality (P = .03) and non-CV hospitalisation (P = .001). In the young-low comorbidity burden and atrial fibrillation-hypertensive cluster, beta-blocker use was associated with statistically significant lower all-cause mortality and non-CV hospitalisation and in the obese-diabetic cluster beta-blocker use was only associated with a statistically significant lower non-CV hospitalisation. The interaction between beta-blocker use and cluster membership for all-cause mortality could potentially be driven by patients with improved EF. However, patient numbers were diminished when excluding those with improved EF and the direction of the associations remained similar. In patients with HFpEF, the association with all-cause mortality and non-CV hospitalisation was heterogeneous across clusters for beta-blockers. It remains to be elucidated how heterogeneity in HFpEF could influence personalized medicine and future clinical trial design.


Interactions between U-937 human macrophages and tyloxapol.
Tyloxapol is reported to prevent macrophages from reacting to endotoxin. However, the intracellular responses that tyloxapol induces in macrophages are still not fully explored. Hence, the objective of this study was to evaluate the intracellular events in macrophages treated with tyloxapol and assess the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Using flow cytometry, we examined intracellular responses in macrophages: reactive oxygen species (ROS) content, mitochondria membrane potential, and cell cycle profiles. We also assessed the antioxidant properties of tyloxapol in endotoxin-activated macrophages. Kinetic hydrogen peroxide production tended to decline with increasing doses. Tyloxapol produced a progressive increase followed by a decline in superoxide anion production in macrophages with increasing doses. Tyloxapol also caused unstable fluctuations in mitochondrial membrane potential. Apoptosis had developed at higher doses after 4h of incubation time. After 2h of tyloxapol-pretreatment, tyloxapol acted as an antioxidant only at lower doses. Most tyloxapol-pretreated cells at lower doses fully recovered from the changes in superoxide anion and hydrogen peroxide production. Our findings contribute to a better understanding of the molecular action of tyloxapol in macrophages and how it protects macrophages against endotoxin.


MDM2 sensitizes a human ovarian cancer cell line.
The purpose of this study was to determine whether overexpression of MDM2 could sensitize the ovarian cancer cell line A2780. The wild-type p53-expressing cell line A2780 was stably transfected with pCMV-MDM2 (A2780-MDM2) or pCMV (A2780-V) as control. MTT assay and clonogenic survival assay were used to measure the cisplatin sensitivity. FACS and host cell (CAT) reactivation assay were used to estimate the change of cell cycle and ability of repairing cisplatin-induced DNA damage. Parental A2780 and A2780-V had similar cisplatin sensitivities, whereas A2780-MDM2 was two- to threefold more sensitive to cisplatin. Repair of cisplatin-induced DNA damage was reduced in A2780 cells overexpressing MDM2, compared to A2780 cells in which wild-type p53 function was intact. After cisplatin treatment, A2780-MDM2 cells showed a pronounced S-phase arrest; however, A2780 cells with intact wild-type p53 arrested primarily in G2/M phase. MDM2 overexpression can increase cisplatin cytotoxicity in A2780, with loss of G1/S checkpoint control and decreased cisplatin-DNA adduct repair. This suggests that ovarian cancers that overexpress MDM2 may be amenable to treatment with platinum compounds.


Radiation recall skin toxicity with bleomycin in a patient with Kaposi sarcoma related to acquired immune deficiency syndrome.
Radiation recall is a recurrence of acute toxicity within a previously quiescent radiation field that occurs with subsequent administration of chemotherapy. A patient with acquired immune deficiency syndrome (AIDS)-related Kaposi sarcoma (KS) who had radiation recall is reported. The patient was participating in a randomized prospective trial of radiation treatment regimens for KS. Each lesion was randomized to one of three possible radiation fractionation schemes. All lesions were photographed and measured before treatment with radiation. Two skin sites developed erythema and dry desquamation 18 days after completion of radiation therapy to a dose of 40 Gy in 20 fractions. These reactions took place after the second dose of bleomycin administered intravenously on a weekly basis. The reactions were exacerbated by oral etoposide therapy, which was started 4 days after the recall phenomenon was noted. Other cutaneous sites treated with 8 Gy in a single fraction and 20 Gy in ten fractions during the same time period showed no sign of recall skin toxicity. The authors believe this to be the first report of radiation recall toxicity after bleomycin therapy and of a radiation dose response related to this phenomenon. The potential for radiation recall toxicity should be considered in treatment decisions pertaining to patients with AIDS-associated KS.


Inhibition of HeLa-S3 cell proliferation and biosynthesis by 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB).
Treatment of HeLa-S3 cells in suspension cultures with 60 microM 5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole (DRB) for 18-30 hr stops the growth of the cell population when treatment is carried out at 37 degrees C in Eagle's spinner culture medium supplemented with 5% fetal bovine serum. The length of the period of no growth after termination of treatment is directly related to the duration of DRB treatment. Upon resumption of growth, the rate becomes exponential and is not distinguishably different from the control rate (doubling time: 19 hr). The growth of the progeny population of the previously DRB-treated cells is as sensitive to inhibition by DRB as the growth of control populations not treated with DRB. After treatment of cells with DRB for 30 hr at 39.5-40 degrees C, the population which grows out has a prolonged doubling time. DRB treatment at 37 degrees C for 5 hr markedly inhibits uridine uptake and cellular RNA synthesis in the presence either of 5 or 15% serum. After treatment for 48 hr in 15% serum, inhibition of RNA synthesis by DRB is significantly decreased. DRB treatment does not inhibit leucine uptake in HeLa cells growing in suspension cultures. Protein synthesis is moderately inhibited in 5% serum and only slightly inhibited in 15% serum after either 5- or 48-hr period of treatment.


Ambient air pollution and epileptic seizures: A panel study in Australia.
Emerging evidence has shown that ambient air pollution affects brain health, but little is known about its effect on epileptic seizures. This work aimed to assess the association between daily exposure to ambient air pollution and the risk of epileptic seizures. This study used epileptic seizure data from two independent data sources (NeuroVista and Seer App seizure diary). In the NeuroVista data set, 3273 seizures were recorded using intracranial electroencephalography (iEEG) from 15 participants with refractory focal epilepsy in Australia in 2010-2012. In the seizure diary data set, 3419 self-reported seizures were collected through a mobile application from 34 participants with epilepsy in Australia in 2018-2021. Daily average concentrations of carbon monoxide (CO), nitrogen dioxide (NO2 ), ozone (O3 ), particulate matter ≤10 μm in diameter (PM10 ), and sulfur dioxide (SO2 ) were retrieved from the Environment Protection Authority (EPA) based on participants' postcodes. A patient-time-stratified case-crossover design with the conditional Poisson regression model was used to determine the associations between air pollutants and epileptic seizures. A significant association between CO concentrations and epileptic seizure risks was observed, with an increased seizure risk of 4% (relative risk [RR]: 1.04, 95% confidence interval [CI]: 1.01-1.07) for an interquartile range (IQR) increase of CO concentrations (0.13 parts per million), whereas no significant associations were found for the other four air pollutants in the whole study population. Female participants had a significantly increased risk of seizures when exposed to elevated CO and NO2 , with RRs of 1.05 (95% CI: 1.01-1.08) and 1.09 (95% CI: 1.01-1.16), respectively. In addition, a significant association was observed between CO and the risk of subclinical seizures (RR: 1.20, 95% CI: 1.12-1.28). Daily exposure to elevated CO concentrations may be associated with an increased risk of epileptic seizures, especially for subclinical seizures.


Drosophila CK2 regulates eye morphogenesis via phosphorylation of E(spl)M8.
The Notch effector E(spl)M8 is phosphorylated at Ser159 by CK2, a highly conserved Ser/Thr protein kinase. We have used the Gal4-UAS system to assess the role of M8 phosphorylation during bristle and eye morphogenesis by employing a non-phosphorylatable variant (M8SA) or one predicted to mimic the 'constitutively' phosphorylated protein (M8SD). We find that phosphorylation of M8 does not appear to be critical during bristle morphogenesis. In contrast, only M8SD elicits a severe 'reduced eye' phenotype when it is expressed in the morphogenetic furrow of the eye disc. M8SD elicits neural hypoplasia in eye discs, elicits loss of phase-shifted Atonal-positive cells, i.e. the 'founding' R8 photoreceptors, and consequently leads to apoptosis. The ommatidial phenotype of M8SD is similar to that in Nspl/Y; E(spl)D/+ flies. E(spl)D, an allele of m8, encodes a truncated protein known as M8*, which, unlike wild type M8, displays exacerbated antagonism of Atonal via direct protein-protein interactions. In line with this, we find that the M8SD-Atonal interaction appears indistinguishable from that of M8*-Atonal, whereas interaction of M8 or M8SA appears marginal, at best. These results raise the possibility that phosphorylation of M8 (at Ser159) might be required for its ability to mediate 'lateral inhibition' within proneural clusters in the developing retina. This is the first identification of a dominant allele encoding a phosphorylation-site variant of an E(spl) protein. Our studies uncover a novel functional domain that is conserved amongst a subset of E(spl)/Hes repressors in Drosophila and mammals, and suggests a potential role for CK2 during retinal patterning.


Biooxidation of hydrogen sulfide to sulfur by moderate thermophilic acidophilic bacteria.
The copper industry utilizes significant amounts of sulfuric acid in its processes, generating sulfate as waste. While sulfate-reducing bacteria can remove sulfate, it produces hydrogen sulfide (H2S) as a byproduct. This study examined the capability of a consortium consisting of Sulfobacillus thermosulfidooxidans and Sulfobacillus acidophilus to partially oxidize H2S to S° at a temperature of 45 °C. A fixed-bed bioreactor, with glass rings as support material and sodium thiosulfate as a model electron donor, was inoculated with the consortium. Formation of biofilms was crucial to maintain the bioreactor's steady state, despite high flow rates. Afterward, the electron donor was changed to H2S. When the bioreactor was operated continuously and with high aeration, H2S was fully oxidized to SO42-. However, under conditions of low aeration and at a concentration of 0.26 g/L of H2S, the consortium was able to oxidize H2S to S° with a 13% yield. S° was discovered attached to the glass rings and jarosite. The results indicate that the consortium could oxidize H2S to S° with a 13% yield under low aeration and at a concentration of 0.26 g/L of H2S. The findings highlight the capability of a Sulfobacillus consortium to convert H2S into S°, providing a potential solution for addressing environmental and safety issues associated with sulfate waste generated by the mining industry.


Polymyxin-based enzyme-linked immunosorbent assay for the detection of Escherichia coli O111 and O26.
Polymyxin-based enzyme-linked immunosorbent assay (polymyxin-ELISA) systems were developed for the detection of Escherichia coli O111 and O26 in ground beef after enrichment. Polymyxin immobilized in the wells of a microtiter plate served as a high affinity adsorbent for lipopolysaccharide (LPS) antigens, which were detected immunoenzymatically using commercially available anti-E. coli O111 or anti-E. coli O26 antisera. The polymyxin-ELISA sensitively detected E. coli strains bearing the O111 and O26 LPS antigens, discriminating between these target strains and a panel of various non-target Gram negative and Gram positive bacteria. The detection of E. coli O111 and O26 strains inoculated into ground beef was achieved after enrichment in either modified trypticase soy broth (TSB) with novobiocin, or the serotype-specific medium TSB supplemented with cefixime and vancomycin (E. coli O111), and the same medium containing potassium tellurite (E. coli O26). The polymyxin-ELISA shows promise as a rapid, simple and inexpensive screening tool for E. coli O111 and O26 in enrichment cultures of ground beef.


Correction: Relationship between self-disclosure to first acquaintances and subjective well-being in people with schizophrenia spectrum disorders living in the community.
[This corrects the article DOI: 10.1371/journal.pone.0223819.].


A novel joint index based on peripheral blood CD4+/CD8+ T cell ratio, albumin level, and monocyte count to determine the severity of major depressive disorder.
Inflammation and immune status are correlated with the severity of major depressive disorder (MDD).The purpose of this study was to establish an optimization model of peripheral blood parameters to predict the severity of MDD. MDD severity in the training and validation cohorts (n = 99 and 97) was classified using the Hamilton Depression Scale, Thirty-eight healthy individuals as controls. Significant severity-associated factors were identified using a multivariate logistic model and combined to develop a joint index through binary logistic regression analysis. The area under the receiver operating characteristic curve (AUC) was used to identify the optimal model and evaluate the discriminative performance of the index. In the training cohort, lower CD4+/CD8+ T cell ratio, albumin level, and a higher monocyte percentage (M%) were significant as operating sociated with severe disease (P < 0.05 for all). The index was developed using these factors and calculated as CD4+/CD8+ T cell ratio, albumin level, and M%, with a sensitivity and specificity of 90 and 70%, respectively. The AUC values for the index in the training and validation cohorts were 0.85 and 0.75, respectively, indicating good discriminative performance. We identified disease severity-associated joint index that could be easily evaluated: CD4+/CD8+ T cell ratio, albumin level, and M%.


Medicare Program; Comprehensive Care for Joint Replacement Payment Model for Acute Care Hospitals Furnishing Lower Extremity Joint Replacement Services. Final rule.
This final rule implements a new Medicare Part A and B payment model under section 1115A of the Social Security Act, called the Comprehensive Care for Joint Replacement (CJR) model, in which acute care hospitals in certain selected geographic areas will receive retrospective bundled payments for episodes of care for lower extremity joint replacement (LEJR) or reattachment of a lower extremity. All related care within 90 days of hospital discharge from the joint replacement procedure will be included in the episode of care. We believe this model will further our goals in improving the efficiency and quality of care for Medicare beneficiaries with these common medical procedures.


Assessment of climate impact on vegetation dynamics over East Africa from 1982 to 2015.
Located across the equator, the East Africa region is among regions of Africa which have previously known the severe vegetation degradation. Some known reasons are associated with the climate change events and unprofessional agricultural practices. For this purpose, the Advanced Very High Resolution Radiometer (AVHRR) version 3 NDVI (NDVI3g) and Climate Research Unit (CRU) datasets for precipitation and temperature were used to assess the impact of climate factors on vegetation dynamics over East Africa from 1982 to 2015. Pearson correlation of NDVI and climate factors were also explored to investigate the short (October - December) rainy seasons. The phenological metrics of the region was also extracted to understand the seasonal cycle of vegetation. The results show that a positive linear trend of 14.50 × 10-4 for mean annual NDVI before 1998, where as a negative linear trend of -9.64 × 10-4 was found after 1998. The Break Point (BP) was obtained in 1998, which suggests to nonlinear responses of NDVI to climate and non-climate drivers. ENSO-vegetation in El-nino years showed a weak teleconnection between ENSO and vegetation growth changes of croplands. Also, the analyzed correlations on NDVI data resulted to the higher correlation between NDVI and precipitation than that with temperature. The Hurst exponent result showed that about, 18.63% pixels exhibited a behavior, typical of random walk (H = 0.5) suggesting that NDVI growth changes may eventually persist, overturn or fluctuate randomly in the future depending on the drivers. Vegetation trends with sustainable (unsustainable) trends were 36.8% (44.6%). Strikingly, about 20% of the total vegetated area showed unsustainable trend from degradation to amelioration. More so, results reveal that the vegetation of the croplands (non-croplands) over East Africa changed insignificantly by 6.9 × 10-5/yr (5.16 × 10-4/yr), suggesting that non-croplands are fast getting reduced Nonetheless, the NDVI growth responses to monthly and seasonal changes in climate were adjudged to be complex and dynamic. Seasonally, the short rainy season showed the higher variability in NDVI than the long rainy season. Also, the DJF, MAM and SON seasons are strongly driven by precipitation variation effect of ENSO versus NDVI series.


Inhibitory effects of Arhgap6 on cervical carcinoma cells.
Ras homology GTPase activation protein 6 (Arhgap6), as a member of the rhoGAP family of proteins, performs vital functions on the regulation of actin polymerization at the plasma membrane during several cellular processes. The role of Arhgap6 in the progression and development of cancer remains nearly unknown. This study aimed at exploring the effects of Arhgap6 on cervical carcinoma. Human cervical cancer cells HeLa and SiHa were transduced with a lentivirus targeting Arhgap6 (Arhgap6+), while CaSki and C4-1 cells were transfected with miRNA. Cell proliferation was identified by Cell Counting Kit-8 (CCK-8). Cell cycle distribution and cell apoptosis were identified by flow cytometry. The capacity of cell migration, invasion, and adhesion were detected by Transwell assay. Further, quantitative real-time PCR (qRT-PCR) and western blot were used to analyze the expression levels of Arhgap6 and several tumor-related genes. Co-immunoprecipitation assay was performed to validate the interaction between Arhgap6 and Rac3 (Ras-related C3 botulinum toxin substrate 3). Results showed that Arhgap6 inhibited cell proliferation, migration, invasion, and adhesion of cervical carcinoma, induced cell apoptosis, and caused cell cycle arrest in the G0/G1 phase (n = 3, p < 0.05). Expression of the tumor suppressor genes and oncogenes were up- and down-regulated respectively by Arhgap6, and Rac3 was proved to be the target of Arhgap6. Besides, in in vivo assays, tumor size and weight were destructed in Arhgap6+ athymic nude mouse. This study indicated that Arhgap6 may play a role in the treatment of cervical cancer as a tumor supressor.


Kidney function following partial or radical nephrectomy for renal cell carcinoma: a population-based study.
The aim of this retrospective study was to compare kidney function in a population-based cohort of renal cell carcinoma (RCC) patients after partial (PN) or radical nephrectomy (RN). Forty-four consecutive RCC patients who had undergone PN in Iceland between 2000 and 2010 were compared with 44 controls matched for tumour, node, metastasis (TNM) stage who had undergone RN during the same period. Estimated glomerular filtration rate (eGFR) and survival were calculated, and predictors of chronic kidney disease (CKD) were evaluated with multivariate analysis. In 16 cases (36%), PN was performed for imperative reasons (single kidney, decreased kidney function or bilateral kidney tumours) but 28 patients had a normal contralateral kidney. The groups were similar regarding preoperative eGFR, median follow-up and TNM stage, but age and American Society of Anesthesiologists (ASA) score were significantly higher in the RN group. Six months after surgery, eGFR was significantly higher in the PN group. By multivariate analysis, RN contributed negatively to eGFR 6 months after surgery (-12.6 ml/1.73 m², p < 0.001) and increased the risk of new-onset CKD (odds ratio = 3.07, 95% confidence interval 1.03-9.79, p = 0.04), compared to PN. At median follow-up of 44 months, no patients in either group had a recurrence of RCC. The 5-year overall survival (Kaplan-Meier) was 100% and 65% in the PN and RN groups, respectively (log-rank test, p < 0.001). eGFR was significantly lower after RN, and these patients were three times more likely to develop new-onset CKD. These findings suggest that PN successfully preserves kidney function compared to RN, with good oncological outcome and survival.


Suppression of stemness and enhancement of chemosensibility in the resistant melanoma were induced by Astragalus polysaccharide through PD-L1 downregulation.
Chemotherapy is commonly used in the clinical treatment of melanoma, but it is prone to resistance leading to the poor effectiveness. The mechanisms of resistance are complicated including the cancer stemness. Astragalus polysaccharide (APS) is one of the active components of traditional Chinese herbal medicine Astragalus Membranaceus. Our previous work was reported that APS had an inhibitory effect on the stemness of melanoma. In this study we established chemo-resistant melanoma cells and found that expression of stemness genes were upregulated in the resistant melanoma cells. And APS could downregulate expression of stemness genes. Furthermore, APS combined with cisplatin (DDP) could significantly slow down the tumor growth in the mouse model induced by DDP-resistant cells. In addition, we found that programmed death-ligand 1 (PD-L1) expression could be downregulated and the PI3K/AKT signaling could be affected by APS. These results suggested that APS could be a potential candidate in combination with chemotherapeutic agents, which might play a role in reducing the occurrence of resistance and improving the prognosis of melanoma patients.


The length of the sanitary napkins can be used as a handier index than pictorial blood loss assessment chart to predict the heavy menstrual bleeding.
Many women with inherited bleeding disorders are not diagnosed because of a lack of appropriate indicators. This study aimed to assess the predictability of the pictorial blood loss assessment chart (PBAC) as an indicator of menorrhagia and identify an easy indicator of menorrhagia resulting from bleeding disorders. A multicenter study enrolled 9 patients with von Willebrand disease (VWD), 23 hemophilia carriers, and 71 controls aged 20-45 years who completed PBACs for two menstrual cycles as well as questionnaires. The PBAC scores of the VWD were significantly higher than those of other groups, even in multivariate analysis with age and sanitary item factors (p = 0.014). A PBAC score of 100 was not an appropriate cutoff because of its low specificity (VWD: sensitivity, 100; specificity, 29.5; hemophilia carriers: 74 and 29.5, respectively). In the ROC analysis, the cutoff of optimal PBAC for VWD was 171 (sensitivity, 66.7; specificity, 72.3; AUC, 0.7296). As the pad length increased, the total length of the pads used during one menstrual period could be a new and easy indicator. However, the cutoff for VWD was 735 cm (sensitivity, 42.9; specificity, 94.3; AUC 0.6837). A threshold could not be established for the hemophilia carrier. Therefore, we multiplied the coefficient by the length of thick pads, which caused a lower PBAC. For the VWD, the sensitivity increased to 85.7 (specificity, 77.1). For the hemophilia carrier, sensitivity (66.7) and specificity (88.6) could be separated from the control. The total length of the pads with a thick-pad adjustment can be a simple method to identify bleeding disorders.


Clinical- and imaging-based prediction of stroke risk after transient ischemic attack: the CIP model.
Predictive instruments based on clinical features for early stroke risk after transient ischemic attack suffer from limited specificity. We sought to combine imaging and clinical features to improve predictions for 7-day stroke risk after transient ischemic attack. We studied 601 consecutive patients with transient ischemic attack who had MRI within 24 hours of symptom onset. A logistic regression model was developed using stroke within 7 days as the response criterion and diffusion-weighted imaging findings and dichotomized ABCD(2) score (ABCD(2) >/=4) as covariates. Subsequent stroke occurred in 25 patients (5.2%). Dichotomized ABCD(2) score and acute infarct on diffusion-weighted imaging were each independent predictors of stroke risk. The 7-day risk was 0.0% with no predictor, 2.0% with ABCD(2) score >/=4 alone, 4.9% with acute infarct on diffusion-weighted imaging alone, and 14.9% with both predictors (an automated calculator is available at http://cip.martinos.org). Adding imaging increased the area under the receiver operating characteristic curve from 0.66 (95% CI, 0.57 to 0.76) using the ABCD(2) score to 0.81 (95% CI, 0.74 to 0.88; P=0.003). The sensitivity of 80% on the receiver operating characteristic curve corresponded to a specificity of 73% for the CIP model and 47% for the ABCD(2) score. Combining acute imaging findings with clinical transient ischemic attack features causes a dramatic boost in the accuracy of predictions with clinical features alone for early risk of stroke after transient ischemic attack. If validated in relevant clinical settings, risk stratification by the CIP model may assist in early implementation of therapeutic measures and effective use of hospital resources.


Association between frailty and chronic pain among older adults: a systematic review and meta-analysis.
Frailty and chronic pain are prevalent among older adults. However, no study has systematically reviewed the association between frailty and chronic pain in older adults. Therefore, we aimed to estimate the prevalence of frailty and prefrailty among older adults with chronic pain and review the longitudinal association between frailty status and chronic pain. Embase, Medline, Pubmed, and Cochrane library were searched from inception to March 2020. The methodological quality of the studies was assessed using the Newcastle Ottawa Scale. Random effect models and Mantel-Haenszel weighting were adopted to synthesize the estimates. Among the initial 846 articles retrieved, 24 were included in the review (12 cross-sectional, and 12 longitudinal). The pooled prevalence in persons with chronic pain was 18% (95% CI 14-23%; I2 = 98.7%) for frailty and 43% (95% CI 36-51%; I2 = 98.2%) for prefrailty. The pooled prevalence of chronic pain was 50% (95% CI 45-55%; I2 = 88.3%) for individuals with frailty and 37% (95% CI 31-42%; I2 = 97.1%) for individuals with prefrailty. Persons with chronic pain were 1.85 (95% CI 1.49-2.28; I2 = 93.2%) times more likely to develop frailty after an average follow-up of 5.8 years compared to those without. Frailty and prefrailty are common in persons with chronic pain. Chronic pain among non-frail older persons significantly predicts the incidence of frailty after an average follow-up of 5.8 years. Future studies should explore the efficacy of different pain management strategies in reducing physical frailty and clarify the association of other types of frailty (cognitive, social and psychological) with chronic pain.