Approaching High-Performance TS-1 Zeolites in the Presence of Alkali Metal Ions via Combination of Adjusting pH Value and Modulating Crystal Size.
Lewis acid zeolites play an important role in industrially important green reactions closely related to fine chemical and biomass conversion. Titanium-doped TS-1 zeolite is a milestone Lewis acid zeolite widely used in industrially significant green oxidation processes with hydrogen peroxide as an oxidant under mild conditions. TS-1 zeolites are normally synthesized in basic conditions under hydrothermal treatment. Up to now, there has still been no success in synthesizing active TS-1 Lewis acid zeolites by using inorganic alkali, e.g., NaOH or KOH as base, which is cheaper and more stable compared to the quaternary ammonium hydroxide or organic amines used in traditional synthesis. Here, an inorganic base of NaOH was employed in synthesizing active TS-1 zeolites for the first time. The crucial factor was the control of adverse effects of sodium cations on the incorporation of active titanium cations. Higher catalytic activity was achieved by further reducing the size of the TS-1 crystal by using the seed-added strategy, which uses the catalytic activity of a commercial catalyst, the production cost being much lower than commercial TS-1 catalysts, indicating great commercial potential and the possibility of preparing other cheap Lewis acid catalysts by using inorganic alkali.


Repetitive Negative Thinking About Suicide: Associations With Lifetime Suicide Attempts.
Repetitive negative thinking has been identified as an important predictor of suicide ideation and suicidal behavior. Yet, only few studies have investigated the effect of suicide-specific rumination, i.e., repetitive thinking about death and/or suicide on suicide attempt history. On this background, the present study investigated, whether suicide-specific rumination differentiates between suicide attempters and suicide ideators, is predictive of suicide attempt history and mediates the association between suicide ideation and suicide attempts. A total of 257 participants with a history of suicide ideation (55.6% female; Age M = 30.56, Age SD = 11.23, range: 18-73 years) completed online measures on suicidality, general and suicide-specific rumination. Suicide-specific rumination differentiated suicide attempters from suicide ideators, predicted suicide attempt status (above age, gender, suicide ideation, general rumination) and fully mediated the association between suicide ideation and lifetime suicide attempts. Overall, though limited by the use of a non-clinical sample and a cross-sectional study design, the present results suggest that suicide-specific rumination might be a factor of central relevance in understanding transitions to suicidal behavior.


Screening for obstructive sleep apnea before coronary angiography.
The prevalence of obstructive sleep apnea (OSA) in patients with suspected coronary heart disease (CHD) is yet to be clarified. This study aimed to investigate the prevalence of OSA before coronary angiography (CAG). We retrospectively evaluated patients with suspected CHD admitted to the Department of Geriatric Cardiology of our hospital between July 2019 and July 2021. OSA was screened using the level III home sleep apnea test before CAG. The prevalence of OSA was then compared between the CHD and non-CHD groups. CHD severity was determined using the Gensini score of CAG results, and OSA severity was graded using the apnea-hypopnea index (AHI). Among the 327 patients, 211 had CHD. In total, 264 patients were diagnosed with OSA (80.7%) (184 patients, CHD group [87.2%]; 80 patients, non-CHD group [69.0%]). The CHD group had a significantly higher prevalence of OSA (P < 0.01) and higher AHI (CHD group 18.76 ± 14.94, non-CHD group 11.56 ± 10.67, P < 0.01). The Gensini score was positively correlated with OSA severity in patients with CHD, and AHI ≥ 20 was a risk factor for CHD (odds ratio: 1.961, 95% confidence interval: 1.065-3.608, P < 0.05). OSA screening before CAG revealed a higher prevalence in CHD patients than in non-CHD patients. The degree of coronary artery obstruction is positively correlated with AHI, and AHI ≥ 20 is a risk factor for CHD. Therefore, attention should be paid to OSA screening and management before CAG in patients with suspected CHD.


A dietary survey in Indian hemodialysis patients.
Malnutrition is a common problem in maintenance hemodialysis (MHD) patients, and compromised intake is an important cause. There is no information available about the nutrient intakes of MHD patients in India. The nutrient intakes of 106 MHD patients were studied cross-sectionally and on follow-up. A 24-hour recall was used on 4 consecutive days. After 2 months on dialysis, the mean energy intake was 29 +/- 6.6 kcal/kg ideal body weight (IBW) and the mean protein intake was.93 +/-.39 g/kg IBW (high biological value [HBV] protein 49% +/- 8.5%). Dietary deficiency of both protein and calories was present in 64.9%. Intake was better on nondialysis days compared with dialysis days, and in women and older patients. On follow-up there was no significant increase in food intake up to 6 months. After that, the total calorie intake increased significantly with a disproportionate drop in high biological value protein consumed and appeared to be derived predominantly from carbohydrate food (mean kcal/kg, 37 +/- 6.9; mean protein g/kg, 0.96 +/- 0.19; ratio of HBV protein to total protein consumed,.42 +/-.09). In summary this study showed suboptimal energy and protein intake in an MHD population. Intakes were further compromised on dialysis days, and with increasing time spent on dialysis, the quality of nutrient intake became poorer.


[Somatopsychic synergism as a variant of masked depression in children and adolescents].
To analyze a variant of a combination of psychopathological (subdepressive) state with inflammatory diseases of non-specific infectious origin. The paper was based on the study of 45 patients, aged from 12 to 19 years, examined using psychopathological and follow-up methods. A detailed somatic examination was performed as well. Authors described a phenomenon of somatopsychic synergism as a variant of a combination of somatic pathology (adenoviral and coccus infections) with subclinical affective syndromes of cyclothymic and schizophrenic origin. This phenomenon is opposed to somatopsychic antagonism which is qualified as a specific form of masked subdepressive states predominantly of asthenic/dynamic structure.


Continuous cerebral blood flow monitoring: What should we do with these extra numbers?
NeoDoppler is a noninvasive monitoring device that can be attached to a patient's head to provide real-time continuous cerebral Doppler evaluation. A feasibility study shows that it can be used in operating theatres during anaesthesia to potentially guide haemodynamic management. We discuss the impact of this new device and which further research would be necessary to find its role in clinical practice.


High prevalence of cardiotropic viruses in myocardial tissue from explanted hearts of heart transplant recipients and heart donors: a 3-year retrospective study from a German patients' pool.
The prevalence of some cardiotropic viruses in virus-associated inflammatory cardiac disease remains controversial. The aim of this study was to examine myocardial tissue samples from explanted hearts of heart transplant recipients and heart donors for nucleic acids of myocardiotropic viruses and to observe the potential risk of viral-induced post-transplantation complications in recipients of cardiac allografts or heart valve homografts. Myocardial tissue samples were analyzed by polymerase chain reaction (PCR) for enteroviruses, adenoviruses, human cytomegalovirus (HCMV), parvovirus B19 (PVB19), and influenza viruses. The results were compared with serologic and histopathologic findings. PCR analysis of 449 myocardial tissue samples from explanted hearts indicated infection in 34 (47%) of 73 heart transplant recipients and 48 (60%) of 80 donors. The prevalence of virus infection in donors aged over 65 years was significantly higher than in heart transplant recipients (p = 0.005) or donors aged under 65 years (p = 0.02). The most frequently detected viruses were enteroviruses (group B coxsackievirus) and adenoviruses. HCMV and PVB19 were found less frequently. All samples were negative for influenza viruses. Although the serologic findings and PCR results for different viruses were discordant in 4% to 27% of cases, PCR and histopathologic findings were highly correlated (88%). The frequent detection of viral genome sequences in myocardial tissue of both heart transplant recipients and heart donors suggests a significant risk for graft-transmitted viral infection in cardiac and heart valve transplant recipients.


Development of a retrobulbar injection technique for ocular surgery and analgesia in dogs.
To develop and compare 3 techniques for retrobulbar injection of local anesthetic agents for ocular surgery and analgesia in dogs. Prospective study. 17 dogs (including 9 cadavers). Inferior-temporal palpebral (ITP), perimandibular, and combined superior-inferior peribulbar injection techniques were compared by assessing the distribution of latex after injection into the orbits of 5 canine cadavers; magnetic resonance imaging (MRI) evaluation of the distribution of contrast agent after injection in the retrobulbar space of 4 canine cadavers; and assessment of the efficacy and MRI evaluation of the anatomic distribution of injections of a lidocainecontrast agent mixture in 4 anesthetized, nonrecovery dogs. By use of the preferred technique (ITP), the ocular effects of lidocaine anesthesia were evaluated in 4 dogs; during a 2-week period after treatment, dogs underwent ophthalmic examination, Schirmer tear testing (STT), intraocular pressure (IOP) measurement, and Cochet-Bonnet esthesiometry. Of the 3 techniques, the ITP technique was the preferred method for retrobulbar administration of anesthetic agent in dogs because it was efficacious (pupil dilation and central rotation of the globe achieved in all eyes), easiest to perform, and provided thorough coverage of the intraconal retrobulbar space without complication. During the 2-week follow-up period, the ITP injection did not significantly affect STT, IOP, or Cochet-Bonnet esthesiometry values in dogs. In dogs, retrobulbar administration of anesthetic agents via the ITP technique is a potential alternative to systemic administration of neuromuscular blocking agents for ophthalmic surgery and provides the additional benefit of local ocular analgesia.


Fos expression in the suprachiasmatic nucleus during photic entrainment of circadian rhythms in retinally damaged rats.
The protein product of the immediate-early gene c-fos is expressed rhythmically in the shell region of the suprachiasmatic nucleus (SCN), the mammalian circadian clock. Recently, we found that exposure to an entraining light pulse caused a suppression of Fos expression in the SCN shell in rats. To study the hypothesis that suppression of Fos in the shell is a correlate of photic entrainment, we used rats that were treated with the retinal neurotoxin monosodium glutamate (MSG) during the neonatal period. In spite of retinal degeneration, MSG-treated rats entrained normally and displayed light-induced suppression of Fos within the SCN shell. These results support the view that light-induced suppression of Fos within the SCN shell is a cellular correlate of photic entrainment.


The Efficacy of Preschool Developmental Indicators as a Screen for Early Primary School-Based Literacy Interventions.
Literacy success lays the foundation for children's later educational, health, and well-being outcomes. Thus, early identification of literacy need is vital. Using data from New Zealand's national preschool health screening program for fiscal years 2010/2011-2014/2015, demographic and health variables from 255,090 children aged 4 years were related to whether they received a literacy intervention in early primary school. Overall, 20,652 (8.1%) children received an intervention. Time-to-event analysis revealed that all considered variables were significantly related to literacy intervention (all p < .01), but the full model lacked reasonable predictive power for population screening purposes (Harrell's c-statistic = .624; 95% CI [.618, .629]). Including more direct literacy measures in the national screening program is likely needed for improvement.


Secretory IgA as an indicator of oro-pharyngeal foot-and-mouth disease virus replication and as a tool for post vaccination surveillance.
A serotype-specific ELISA was developed to detect foot-and-mouth disease virus (FMDV) specific IgA antibody in the saliva of cattle, and the method was evaluated for its feasibility in detecting serotype O FMDV carrier animals, particularly amongst vaccinated cattle that had subsequently become sub-clinically infected. For this purpose, saliva samples were collected from naïve cattle (n = 173), FMDV challenged cattle (n = 10), FMDV vaccinated cattle (n = 40) and FMDV vaccinated-and-challenged cattle (n = 40). A subset of 29 cattle was sampled for 105-168 days after challenge. The FMDV infection status of each of the cattle was determined by virus isolation and RT-PCR tests on oesophago-pharyngeal fluids and the ability of the IgA test to detect viral infection and persistence was compared to an ELISA for the detection of serum antibodies against the 3ABC non-structural proteins of FMDV. Eleven out of twelve vaccinated cattle that were shown to be persistently infected with FMDV up to or beyond 28 days post challenge, were also detected by the IgA test on saliva. With some modification and further validation, this test could be useful in post-vaccination surveillance to help confirm the absence of sub-clinical infection in order to regain the FMD-free status of a region or country.


The ly49 gene family. A brief guide to the nomenclature, genetics, and role in intracellular infection.
Understanding the Ly49 gene family can be challenging in terms of nomenclature and genetic organization. The Ly49 gene family has two major gene nomenclature systems, Ly49 and Killer Cell Lectin-like Receptor subfamily A (klra). Mice from different strains have varying numbers of these genes with strain specific allelic variants, duplications, deletions, and pseudogene sequences. Some members activate NK lymphocytes, invariant NKT (iNKT) lymphocytes and γδ T lymphocytes while others inhibit killing activity. One family member, Ly49Q, is expressed only on myeloid cells and is not found on NK, iNKT, or γδ T cells. There is growing evidence that these receptors may regulate not just the immune response to viruses, but other intracellular pathogens as well. Thus, this review's primary goal is to provide a guide for researchers first encountering the Ly49 gene family and a foundation for future studies on the role that these gene products play in the immune response, particularly the response to intracellular viral and bacterial pathogens.


Downregulation of AAA-domain-containing protein 2 restrains cancer stem cell properties in esophageal squamous cell carcinoma via blockade of the Hedgehog signaling pathway.
Esophageal squamous cell carcinoma (ESCC) ranks among the five most common cancers in China and has a five-year survival rate of less than 15%. The transcription factor ATPase-family AAA-domain-containing protein 2 (ATAD2) has potential as a therapeutic target in various tumors, and microarray-based gene expression profiling reveals dysregulation of ATAD2 specifically in ESCC. Here we investigated whether ATAD2 could mediate a regulation of cancer stem cell (CSC) biological functions in ESCC. Immunohistochemical staining, reverse transcription quantitative polymerase chain reaction, and Western blot assays all revealed upregulation of ATAD2 in ESCC tissues and cell lines, which furthermore correlated with progression of ESCC. In loss-of-function experiments, silencing of ATAD2 inhibited activation of the Hedgehog signaling pathway, as indicated by reduced expression of glioma-associated oncogene family zinc finger 1 (Gli1), smoothened frizzled class receptor (SMO), and patched 1 (PTCH1). Investigations with 5-ethynyl-2'-deoxyuridine (EdU), Transwell assay, scratch test, flow cytometry, and colony formation assay showed that silencing of ATAD2 or inhibiting the Hedgehog signaling decreased the proliferation, invasion, and migration abilities along with colony formation, but elevated the apoptosis rate of CSCs. Furthermore, in vivo experiments validated the suppressive effect of siRNA-mediated ATAD2 silencing on tumor growth in nude mice. Thus, downregulation of ATAD2 can seemingly restrain the malignant phenotypes of ESCC cells through inhibition of the Hedgehog signaling pathway.


An evidence map of systematic reviews on models of outpatient care for patients with chronic heart diseases.
Chronic heart disease affects millions of people worldwide and the prevalence is increasing. By now, there is an extensive literature on outpatient care of people with chronic heart disease. We aimed to systematically identify and map models of outpatient care for people with chronic heart disease in terms of the interventions included and the outcomes measured and reported to determine areas in need of further research. We created an evidence map of published systematic reviews. PubMed, Cochrane Library (Wiley), Web of Science, and Scopus were searched to identify all relevant articles from January 2000 to June 2021 published in English or German language. From each included systematic review, we abstracted search dates, number and type of included studies, objectives, populations, interventions, and outcomes. Models of care were categorised into six approaches: cardiac rehabilitation, chronic disease management, home-based care, outpatient clinic, telemedicine, and transitional care. Intervention categories were developed inductively. Outcomes were mapped onto the taxonomy developed by the COMET initiative. The systematic literature search identified 8043 potentially relevant publications on models of outpatient care for patients with chronic heart diseases. Finally, 47 systematic reviews met the inclusion criteria, covering 1206 primary studies (including double counting). We identified six different models of care and described which interventions were used and what outcomes were included to measure their effectiveness. Education-related and telemedicine interventions were described in more than 50% of the models of outpatient care. The most frequently used outcome domains were death and life impact. Evidence on outpatient care for people with chronic heart diseases is broad. However, comparability is limited due to differences in interventions and outcome measures. Outpatient care for people with coronary heart disease and atrial fibrillation is a less well-studied area compared to heart failure. Our evidence mapping demonstrates the need for a core outcome set and further studies to examine the effects of models of outpatient care or different interventions with adjusted outcome parameters. PROSPERO (CRD42020166330).


(E)-3-Thia-1,5(1,3)-dibenzena-cyclo-undeca-phan-8-ene-6,11-dione 3,3-dioxide.
The molecular structure of the title cyclophane, C20H18O4S, has two benzyl groups, a sulfone group, and two carbonyl groups adjacent to a double bond. The phenyl rings do not show intra-molecular stacking.


Age and duration of illness as predictors of ventricular brain ratio (VBR) size in chronic schizophrenic patients. A stepwise regression analysis study.
The CT scans of 18 chronic schizophrenic patients and 17 controls were evaluated for Ventricular Brain Ratio (VBR) size. A trend for the patient group to have larger VBR than controls was present but did not reach statistical significance at the 5% level. Age was found to be an important correlate of VBR within the patient group but not among controls. In a stepwise multiple-regression model age, among other independent variables, can account for 47% of VBR variance in schizophrenic patients. Linear regression analysis did not reveal significant association between VBR and age in control subjects.


Expression homeostasis during DNA replication.
Genome replication introduces a stepwise increase in the DNA template available for transcription. Genes replicated early in S phase experience this increase before late-replicating genes, raising the question of how expression levels are affected by DNA replication. We show that in budding yeast, messenger RNA (mRNA) synthesis rate is buffered against changes in gene dosage during S phase. This expression homeostasis depends on acetylation of H3 on its internal K56 site by Rtt109/Asf1. Deleting these factors, mutating H3K56 or up-regulating its deacetylation, increases gene expression in S phase in proportion to gene replication timing. Therefore, H3K56 acetylation on newly deposited histones reduces transcription efficiency from replicated DNA, complementing its role in guarding genome stability. Our study provides molecular insight into the mechanism maintaining expression homeostasis during DNA replication.


Torsion of the gallbladder, localized in right subphrenic space in a patient with liver cirrhosis.
We report a case of torsion of the gallbladder displaced under the right subphrenic space in a patient with liver cirrhosis. An 82-year-old Japanese woman was admitted to our hospital for acute pain in the right upper quadrant. Clinical features suggested gallbladder torsion. She was under treatment for hepatitis C virus-related cirrhosis at our hospital. Abdominal CT showed the swollen fundus and body of the gallbladder under the right subphrenic space. Emergency laparoscopic cholecystectomy was performed. Intraoperative findings included a grossly necrotic gallbladder in the right subphrenic space with 360° clockwise torsion, together with liver cirrhosis and localized peritonitis. The clinical features and imaging findings in this rare case of misplaced gallbladder in right subphrenic space resembled those described in typical strangulated gallbladder. The displacement was probably related to right liver lobe atrophy associated with liver cirrhosis. Appropriate diagnosis and prompt surgical treatment are essential for a positive outcome.


Purification, structural characterization and antioxidant activities of two neutral polysaccharides from persimmon peel.
Two neutral polysaccharides (PPP1-1 and PPP1-2) were purified from persimmon peel. PPP1-1 (21.84 kDa) was mainly composed of arabinose (22.92 %), galactose (21.09 %), glucose (35.13 %), and xylose (19.09 %), while PPP1-2 (10.42 kDa) mainly contained arabinose (32.98 %), galactose (20.81 %), glucose (26.86 %), xylose (10.46 %), and mannose (7.63 %). Methylation and NMR spectra analysis demonstrated that the backbone of PPP1-1 appeared to be →6)-α-D-Glcp-(1→, →2,6)-α-D-Glcp-(1→, →5)-α-L-Araf-(1→, and →3,5)-α-L-Araf-(1 → residues with branches consisting of →3)-α-L-Araf-(1→, →4)-α-D-Glcp-(1→, →3)-β-D-Galp-(1→, →4)-β-D-Galp-(1→, →4)-β-D-Xylp-(1→, →6)-β-D-Galp-(1→, →4)-β-D-Manp-(1→, and α-L-Araf-(1 → residues. The main chain of PPP1-2 was composed of →6)-α-D-Glcp-(1→, →5)-α-L-Araf-(1→, and →3,5)-α-L-Araf-(1 → residues with branches consisting of →3)-α-L-Araf-(1→, →1,2)-α-D-Glcp-(6→, →4)-α-D-Glcp-(1→, →3)-β-D-Galp-(1→, →4)-β-D-Galp-(1→, →6)-β-D-Galp-(1→, →4)-β-D-Xylp-(1→, →4,6)-α-D-Glcp-(1→, and →4)-β-D-Manp-(1 → residues and terminal of α-L-Araf-(1 → residue. PPP1-2 exhibited stronger antioxidant activities and better thermal stability than PPP1-1. Our results provided the foundation for further investigating the structure and biological activities of persimmon peel polysaccharides and highlighted their potential to become potential antioxidants in functional food.


Modeling and simulation of sexual activity daily diary data of patients with female sexual arousal disorder treated with sildenafil citrate (Viagra).
To develop a model to explore the dose-response of sildenafil citrate in patients with female sexual arousal disorder (FSAD) based on telephone sexual activity daily diary (TSADD) data obtained in double-blind, placebo controlled clinical studies. Data were available on 614 patients with FSAD. A parametric model (Weibull distribution) was developed to describe the probability density function of the time between sexual events. Orgasm satisfaction scores and overall sexual satisfaction scores were simultaneously modeled as ordered categorical variables. Simulations were performed to evaluate the expected clinical response in patients with FSAD. The expected time between sexual events was approximately 3.5 days. Satisfaction scores increased with time to achieve a plateau after 3 to 4 weeks on treatment. The expected probability of satisfying orgasm (score of 3 and higher) ranged from 34.7% for placebo to 41.6% for 100 mg sildenafil citrate. Treatment effect (difference from placebo) was 6.9% for 100 mg sildenafil citrate, ranging from 0.6 to 24.7% for testosterone levels of 0.1 to 4.0 pg/ml. The treatment effect in postmenopausal women was larger than in premenopausal women. A modeling and simulation framework to support drug development in FSAD was developed. Sildenafil citrate demonstrated a dose-dependent effect in patients with FSAD.


The N-methyl-D-aspartate antagonists CGS 19755 and CPP reduce ischemic brain damage in gerbils.
N-Methyl-D-aspartate (NMDA) antagonists reduce ischemic brain damage and associated hypermotility. Two potent, selective and competitive NMDA antagonists, cis-4-(phosphonomethyl)-2-piperidine-carboxylic acid (CGS 19755) and 4-(3-phosphonopropyl)-2-piperazine-carboxylic acid (CPP), were characterized in the gerbil ischemia model with respect to dose-response and time course effects. Both drugs were effective in reducing ischemia-induced hippocampal brain damage as well as hypermotility. In this model, CGS 19755 was more potent than CPP, and had protective effects when given after longer delays between ischemia and drug administration.


Mutational analysis of nicotinic acetylcholine receptor beta2 subunit gene (CHRNB2) in a representative cohort of Italian probands affected by autosomal dominant nocturnal frontal lobe epilepsy.
Twenty-four autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) probands were analyzed for the presence of V287L and V287M mutations in the CHRNB2 gene, which have been recently associated with the disease. In all patients, the involvement of the two additional loci reported as being associated with ADNFLE (CHRNA4 gene and chromosome 15q24 region) had been previously excluded. Mutational screening was performed by sequencing a polymerase chain reaction-amplified CHRNB2 DNA fragment, spanning the whole exon 5, which contains the V287L and V287M mutations and codes for approximately 65% of the mature protein. In none of the patients were mutations in the analyzed region of CHRNB2 found. These data, obtained in the largest ADNFLE cohort so far analyzed, demonstrate the rarity of the identified CHRNB2 mutations in ADNFLE patients.


Immobilization of glucose oxidase on chitosan-based porous composite membranes and their potential use in biosensors.
The glucose oxidase (GOx) enzyme was immobilized on chitosan-based porous composite membranes using a covalent bond between GOx and the chitosan membrane. The chitosan-based porous membranes were prepared by the combination of the evaporation- and non-solvent-induced phase separation methods. To increase the membrane conductivity, carbon nanotubes (CNTs) were added to the chitosan solution. The resulting membranes were characterized in terms of water permeability, surface morphology and surface chemistry. Enzyme immobilization was performed on the chitosan membranes with and without activation using glutaraldehyde (GA). Three different configurations of working electrodes were evaluated to investigate the potential use of the modified membranes in biosensors. The results show that enzyme immobilization capacity was greater for membranes that had been activated than for membranes that had not been activated. In addition, activation increased the stability of the enzyme immobilization. The immobilization of GOx on chitosan-based membranes was influenced by both pH and the concentration of the enzyme solution. The presence of CNTs significantly increased the electrical conductivity of the chitosan membranes. The evaluation of three different configurations of working electrodes suggested that the third configuration, which was composed of an electrode-mediator-(chitosan and carbon nanotube) structure and enzyme, is the best candidate for biosensor applications.


The impact of gestational sac size on the effectiveness and safety of high intensity focused ultrasound combined with ultrasound-guided suction curettage treatment for caesarean scar pregnancy.
To evaluate the correlation between the gestational sac size and the effect and safety of high intensity focused ultrasound (HIFU) combined with ultrasound-guided suction curettage for caesarean scar pregnancy (CSP). Seventy-six patients with CSP were enrolled. Based on their gestational sac size, patients were divided into three groups: Group 1 (n = 16, 10-20 mm), Group 2 (n = 28, 21-30 mm) and Group 3 (n = 32, >30 mm). All of them were treated by HIFU combined with ultrasound-guided suction curettage. Baseline characteristics, parameters and adverse events of HIFU, and intraoperative hemorrhage during ultrasound-guided suction curettage were recorded. The median treatment time and average treatment intensity of HIFU in Group 3 were significantly higher than Group 1 (p < .05); the median HIFU treatment power in Group 2 and Group 3 were both significantly higher than that of Group 1 (p < .05). The median sonication time of HIFU in Group 3 was significantly longer than patients in the other two groups (p < .05). The size of the gestational sac had a positive correlation with all the above-mentioned parameters of HIFU and blood loss during ultrasound-guided suction curettage (p < .05). No statistically significant differences were observed among the three groups in the duration of vaginal bleeding post-curettage and the time necessary for serum β-hCG to return to normal levels (p > .05). HIFU combined with ultrasound-guided suction curettage is a safe and effective clinical approach for CSP. Gestational sac size is a meaningful factor for predicting the efficacy and safety of HIFU treatment and hemorrhage during ultrasound-guided suction curettage.


A comparative SAR study of thrombin receptor derived non peptide mimetics: importance of phenyl/guanidino proximity for activity.
Thrombin, the most potent physiological platelet agonist interacts with cells through a specific G protein-coupled receptor which has been cloned and sequenced. Synthetic thrombin receptor peptides (TRAPs) comprising the first 5 amino acids (SFLLR and SFLLR-NH2) of the new N-terminus tethered ligand of the thrombin receptor that is generated by thrombin's proteolytic activity were found to cause full platelet aggregation. During the screening of novel thrombin receptor derived non-peptide mimetics in the platelet aggregation assay we found that 1-phenylacetyl-4-(6-guanidohexanoyl)-piperazine (1) and 1-(6-guanidohexanoyl)-4-(phenylacetylamidomethyl)-piperidine (2) exerted in vitro antagonist activities (56% and 40% correspondingly) as it is depicted by the platelet aggregation assay. Using Molecular Modeling, the synthetic compounds were overlayed with SFFLR. All three superimposed low energy structures had Phe and Arg amino acids in spatial close proximity. The superimposition results revealed that 1 resembled more the stereoelectronic environment of SFLLR than 2. This difference may be related to their different antagonist efficacy.


A Stochastic Model of Gene Expression with Polymerase Recruitment and Pause Release.
Transcriptional bursting is a major source of noise in gene expression. The telegraph model of gene expression, whereby transcription switches between on and off states, is the dominant model for bursting. Recently, it was shown that the telegraph model cannot explain a number of experimental observations from perturbation data. Here, we study an alternative model that is consistent with the data and which explicitly describes RNA polymerase recruitment and polymerase pause release, two steps necessary for messenger RNA (mRNA) production. We derive the exact steady-state distribution of mRNA numbers and an approximate steady-state distribution of protein numbers, which are given by generalized hypergeometric functions. The theory is used to calculate the relative sensitivity of the coefficient of variation of mRNA fluctuations for thousands of genes in mouse fibroblasts. This indicates that the size of fluctuations is mostly sensitive to the rate of burst initiation and the mRNA degradation rate. Furthermore, we show that 1) the time-dependent distribution of mRNA numbers is accurately approximated by a modified telegraph model with a Michaelis-Menten like dependence of the effective transcription rate on RNA polymerase abundance, and 2) the model predicts that if the polymerase recruitment rate is comparable or less than the pause release rate, then upon gene replication, the mean number of RNA per cell remains approximately constant. This gene dosage compensation property has been experimentally observed and cannot be explained by the telegraph model with constant rates.


A case of benign cementoblastoma.
A rare case of benign cementoblastoma is reported. Active cementoblasts adding cementoid tissue were observed histologically by means of specific staining for unmineralized matrix of hard tissue. A polarizing microscope and an x-ray diffractometer were used to clarify the cementum-like tissue of benign cementoblastoma. The collagen bundles of tumor tissue showed irregular and random arrangements under polarized light. The qualitative analysis revealed that the mineralized component was composed of low-crystalline hydroxylapatite.


Uptake of dopamine by cultured monkey amniotic epithelial cells.
In this study, the ability of monkey amniotic epithelial (MAE) cells to take up dopamine was tested by incubating the cells in buffer containing unlabeled dopamine under different experimental conditions followed by assaying dopamine content using high performance liquid chromatography with electrochemical detection. Results showed the capability of MAE cells to take up dopamine in a time- and concentration-dependent fashion, and also this uptake is sodium-dependent. Further, selective dopamine transporter blockers inhibited dopamine uptake with rank order of potency that is consistent with the pharmacology of the dopamine transporter. These results suggest that MAE cells may be potential model to study dopamine uptake and release, and to explore new drugs affecting these processes.


Influence of water activity on deoxynivalenol accumulation in wheat.
The influence of water activity (aw) on deoxynivalenol accumulation in wheat at 25°C was studied. Gnotobiotic grains were conditioned at different aw levels, inoculated with a toxigenic Fusarium graminearum strain, and incubated for ten weeks. The highest accumulation of deoxynivalenol (1130 ug/kg) was detected at aw 0.980. At aw 0.945 and 0.925 the maximum quantities of toxin accumulated were 113 ug/kg and 93 ug/kg respectively. Deoxynivalenol was not detected in the substrate at aw 0.900. Results suggest that intermediate aw levels (0.97 - 0.92) are particularly critical at post harvest time because those are conditions under which deoxynivalenol production is most likely to be initiated naturally.


Supercurrent diode effect and finite-momentum superconductors.
SignificanceOur work shows a fascinating application of finite-momentum superconductivity, the supercurrent diode effect, which is being reported in a growing number of experiments. We show that, under external magnetic field, Cooper pairs can acquire finite momentum so that critical currents in the direction parallel and antiparallel to the Cooper pair momentum become unequal.


New Hope in Prostate Cancer Precision Medicine? miRNA Replacement and Epigenetics.
SPINK1 +/ETS - prostate cancer is an aggressive disease with poor clinical outcome. New data suggest a novel treatment by upregulating the expression of miR-338-5p/-421 through epigenetic modulation or by miRNA replacement. This is a new and interesting concept that warrants further exploration in clinical trials.See related article by Bhatia et al., p. 2755.


Nurse-led multi-component behavioural activation programme to improve health outcomes in patients with atrial fibrillation: a mixed-methods study and feasibility analysis.
Patients with atrial fibrillation (AF) play passive roles in disease management. This study aimed to examine the feasibility and preliminary effects of an empowerment-based care model, titled 'the nurse-led multi-component behavioural activation (N-MBA) programme', on health-related quality of life, AF knowledge, psychological outcomes, medication adherence, and treatment decision-making in patients with AF. This mixed-methods study comprised a pilot randomized controlled trial and a qualitative study. Patients with AF who had a moderate-to-high risk of stroke but were not prescribed oral anticoagulants were recruited. Forty participants were recruited and randomized in a 1:1 ratio to receive either the N-MBA programme or standard care. The 13-week programme comprised care components that prepared patients for shared decision-making, an empowerment-based educational module on AF self-care, and continuous support through telephone calls. The programme was feasible, and the overall attendance rate was 82.5%. The participants gave excellent ratings in the satisfaction survey. The N-MBA group showed greater improvements in health-related quality of life (HRQoL) and AF knowledge than the standard care group at the immediate post intervention and 6-month follow-up time points. No significant between-group changes in medication adherence, anxiety, and depression were detected. Participants in the N-MBA group actively raised concerns about AF and its treatment with their attending doctors. The qualitative data were consistent with the quantitative data, indicating that the programme built a comprehensive knowledge base of AF and self-care behaviours. The N-MBA programme is feasible and acceptable to patients with AF. It improved patients' AF knowledge, treatment-related decision-making, and HRQoL. ClinicalTrials.gov NCT03924739.


Are Oral and Maxillofacial Surgery Residents Trained Adequately in Alloplastic Total Temporomandibular Joint Replacement?
To assess the current level of experience and training that oral and maxillofacial surgery (OMS) residents receive in alloplastic temporomandibular joint (TMJ) total joint replacement (TJR) at OMS training programs in the United States. A questionnaire was developed using REDCap (Chicago, IL), and an on-line link was emailed to the program directors of all 101 OMS training programs in the United States accredited by the Commission on Dental Accreditation. The questionnaire included 20 questions related to the program's alloplastic TMJ TJR curriculum and clinical experience. In addition, a Likert scale was used to assess the respondents' opinions on resident training and the future of alloplastic TMJ TJR education and its clinical effect and usage. The study sample included 53 respondents (52.5%). Of the 53 responding OMS programs, 94% provide TMJ TJR didactic lectures presented by OMS faculty. The alloplastic TMJ TJR procedures averaged 0 to 6 annually per program; however, 25% of the programs reported more than 10 cases annually. Infection and continued pain were reported as the most common reasons for alloplastic TMJ TJR device replacement. It appears that adequate didactic and clinical training is being provided to OMS residents in alloplastic TMJ TJR during their training. Additional studies might elucidate the actual geographic distribution of OMS surgeons who perform alloplastic TMJ TJR procedures.


Effect on phoneme duration control of three utterance-length conditions in an apractic patient.
Phoneme duration control in utterances of various lengths was investigated in one apractic subject. Results indicate a loss of segment duration control and a speeding of intrasyllabic articulatory rates in apraxia. Findings are related to a theory of apractic speech dysfunction.


Cholesteryl ester storage disease in a young child presenting as isolated hepatomegaly treated with simvastatin.
Cholesteryl ester storage disease (CESD) is an autosomal recessive disorder resulting from lysosomal acid lipase deficiency and is usually characterized by hepatomegaly and hyperlipidemia. This paper reports a two-year-old boy who had hepatosplenomegaly, hyperlipidemia and hypertransaminasemia determined incidentally. The liver biopsy sample was orange-yellow in appearance. Microscopically, microvesicular steatosis and birefringent crystals were seen in liver biopsy. The diagnosis of CESD was confirmed by the reduced human acid lipase activity in peripheral leukocytes. Simvastatin therapy was given and tolerated without side effects. Our patient is the youngest reported case in the literature treated with 3-hydroxy 3-methyl glutaryl (HMG) CoA reductase inhibitor.


IKK-i/IKKepsilon controls constitutive, cancer cell-associated NF-kappaB activity via regulation of Ser-536 p65/RelA phosphorylation.
Nuclear factor kappaB (NF-kappaB) has been studied extensively as an inducible transcriptional regulator of the immune and inflammatory response. NF-kappaB activation downstream of lipopolysaccharide or cytokine stimulation is controlled by the IkappaB kinase complex, which contains IKKalpha and IKKbeta. Significantly, the constitutive activity of NF-kappaB has been implicated as an important aspect of many cancer cells, but mechanisms associated with this activity are poorly understood. An inducible kinase, IKK-i/IKKepsilon, related to the catalytic forms of the IkappaB kinase, has been studied as an anti-viral, innate immune regulator through its ability to control the activity of the transcription factors IRF-3 and IRF-7. Here, we demonstrate that IKK-i/IKKepsilon is expressed in a number of cancer cells and is involved in regulating NF-kappaB activity through its ability to control basal/constitutive, but not cytokine-induced, p65/RelA phosphorylation at Ser-536, a modification proposed to contribute to the transactivation function of NF-kappaB. Knockdown of IKK-i/IKKepsilon or expression of a S536A mutant form of p65 suppresses HeLa cell proliferation. The data indicate a role for IKK-i/IKKepsilon in controlling proliferation of certain cancer cells through regulation of constitutive NF-kappaB activity.


Fast-lived Hosts and Zoonotic Risk.
Because most emerging human pathogens originate in mammals, many studies aim to identify host traits that determine the risk of sourcing zoonotic outbreaks. Studies regularly assert that 'fast-lived' mammal species exhibiting greater fecundity and shorter lifespans tend to host more zoonoses; however, the causes of this association remain poorly understood and they cover a range of immune and nonimmune mechanisms. We discuss these drivers in the context of evolutionary ecology and wildlife-human interactions. Ultimately, differentiating these mechanisms will require linking interspecific variation in life history with immunity, pathogen diversity, transmissibility, and zoonotic risk, and critical data gaps currently limit our ability to do so. We highlight sampling and analytical frameworks to address this gap and to better inform zoonotic reservoir prediction.


Differential modulation of feline defensive rage behavior in the medial hypothalamus by 5-HT1A and 5-HT2 receptors.
Previous studies have established that the expression of defensive rage behavior in the cat is mediated over reciprocal pathways that link the medial hypothalamus and the dorsolateral quadrant of the midbrain periaqueductal gray matter (PAG). The present study was designed to determine the roles played by 5-HT(1A) and 5-HT(2C) receptors in the medial hypothalamus on the expression of defensive rage behavior elicited from electrical stimulation of the PAG. Monopolar stimulating electrodes were placed in the midbrain PAG from which defensive rage behavior could be elicited by electrical stimulation. During the course of this study, defensive rage was determined by measuring the latency of the "hissing" component of this behavior. Cannula-electrodes were implanted into sites within the medial hypothalamus from which defensive rage behavior could also be elicited by electrical stimulation in order that serotonergic compounds could be microinjected into behaviorally identifiable regions of the hypothalamus at a later time. Microinjections of the 5-HT(1A) receptor agonist 8-OHDPAT (0.1, 1.0 and 3.0 nmol) into the medial hypothalamus suppressed PAG-elicited hissing in a dose-dependent manner. Administration of the 5-HT(1A) antagonist p-MPPI (3.0 nmol) blocked the suppressive effects of 8-OHDPAT upon hissing. The suppressive effects of 8-OHDPAT were specific to defensive rage behavior because this drug (3 nmol) facilitated quiet biting attack. Microinjections of the 5-HT(2C) receptor agonist (+/-)-DOI hydrochloride into the medial hypothalamus (0.5, 1.0, and 3.0 nmol) facilitated the occurrence of PAG-elicited hissing in a dose-dependent manner. In turn, these facilitating effects were blocked by pretreatment with the selective 5-HT(2) antagonist, LY-53,857, which was microinjected into the same medial hypothalamic site. The findings of this study provide evidence that activation of 5-HT(1A) and 5-HT(2) receptors within the medial hypothalamus exert differential modulatory effects upon defensive rage behavior elicited from the midbrain PAG of the cat.


Addressing recall bias in (post-)conflict data collection and analysis: lessons from a large-scale health survey in Colombia.
Much applied research on the consequences of conflicts for health suffers from data limitations, particularly the absence of longitudinal data spanning pre-, during- and post-conflict periods for affected individuals. Such limitations often hinder reliable measurement of the causal effects of conflict and their pathways, hampering also the design of effective post-conflict health policies. Researchers have sought to overcome these data limitations by conducting ex-post surveys, asking participants to recall their health and living standards before (or during) conflict. These questions may introduce important analytical biases due to recall error and misreporting. We investigate how to implement ex-post health surveys that collect recall data, for conflict-affected populations, which is reliable for empirical analysis via standard quantitative methods. We propose two complementary strategies based on methods developed in the psychology and psychometric literatures-the Flashbulb and test-retest approaches-to identify and address recall bias in ex-post health survey data. We apply these strategies to the case study of a large-scale health survey which we implemented in Colombia in the post-peace agreement period, but that included recall questions referring to the conflict period. We demonstrate how adapted versions of the Flashbulb and test-retest strategies can be used to test for recall bias in (post-)conflict survey responses. We also show how these test strategies can be incorporated into post-conflict health surveys in their design phase, accompanied by further ex-ante mitigation strategies for recall bias, to increase the reliability of survey data analysis-including by identifying the survey modules, and sub-populations, for which empirical analysis is likely to yield more reliable causal inference about the health consequences of conflict. Our study makes a novel contribution to the field of applied health research in humanitarian settings, by providing practical methodological guidance for the implementation of data collection efforts in humanitarian contexts where recall information, collected from primary surveys, is required to allow assessments of changes in health and wellbeing. Key lessons include the importance of embedding appropriate strategies to test and address recall bias into the design of any relevant data collection tools in post-conflict or humanitarian contexts.


Effects of friction at the digit-object interface on the digit forces in multi-finger prehension.
The effects of surface friction at the digit-object interface on digit forces were studied when subjects (n=8) statically held an object in a five-digit grasp. The friction conditions were SS (all surfaces are sandpaper), RR (all are rayon), SR (S for the thumb and R for the four fingers), and RS (the reverse of SR). The interaction effects of surface friction and external torque were also examined using five torques (-0.5, -0.25, 0, +0.25, +0.5 Nm). Forces and moments exerted by the digits on a handle were recorded. At zero torque conditions, in the SS and RR (symmetric) tasks the normal forces of the thumb and virtual finger (VF, an imagined finger with the mechanical effect equal to that of the four fingers) were larger for the RR than the SS conditions. In the SR and RS (asymmetric) tasks, the normal forces were between the RR and SS conditions. Tangential forces were smaller at the more slippery side than at the less slippery side. According to the mathematical optimization analysis decreasing the tangential forces at the more slippery sides decreases the cost function values. The difference between the thumb and VF tangential forces, DeltaF (t), generated a moment of the tangential forces (friction-induced moment). At non-zero torque conditions the friction-induced moment and the moment counterbalancing the external torque (equilibrium-necessitated moment) could be in same or in opposite directions. When the two moments were in the same direction, the contribution of the moment of tangential forces to the total moment was large, and the normal forces were relatively low. In contrast, when the two moments were in opposite directions, the contribution of the moment of tangential forces to the total moment markedly decreased, which was compensated by an increase in the moment of normal forces. The apparently complicated results were explained as the result of summation of the friction-related (elemental) and torque-related (synergy) components of the central commands to the individual digits.


In vitro immune responses to hepatitis B surface antigen (Pre-S2 and S) following remote infection by hepatitis B virus in humans.
In this report we evaluate the human immune response to hepatitis B surface antigen (HBsAg) following remote infection with hepatitis B virus (HBV). HBsAg-reactive lymphocytes can be readily demonstrated in the peripheral blood of individuals with established immunity following infection with HBV. In vitro stimulation with small doses of plasma-derived HBsAg, yeast-derived HBsAg (S region) or pre-S2 peptide will induce specific IgG to HBsAg (anti-HBs) in the absence of a polyclonal increase in total IgG. The pre-S2 peptide will stimulate, in a T cell-dependent fashion, the in vitro production of anti-HBs with specificity for the S domain. This anti-HBs production is mediated by pre-S2-stimulated soluble T-cell factors. Peripheral blood mononuclear cells from individuals with established immunity proliferate to the yeast-derived HBsAg but not to the plasma-derived HBsAg or pre-S2 peptide. The chronic HBsAg carriers do not produce anti-HBs following stimulation with HBsAg regardless of the source or component of antigen used. Different study protocols failed to demonstrate HBsAg-specific responses in the peripheral blood mononuclear cells of chronic carriers.


Effect of prostaglandins E2 and D2 on presynaptic NMDA receptors in rat cerebral cortex.
We studied the effect of prostaglandins on presynaptic NMDA receptors. Prostaglandin E2 inhibited NMDA-induced (45)Ca2+ uptake by synaptosomes in low concentrations (IC50 approximately 10 microM), but potentiated it in higher concentrations. Prostaglandin D2 increased (45)Ca2+ uptake by synaptosomes during stimulation of NMDA receptors. Our results indicate that prostaglandins D2 and E2 modulate function of presynaptic NMDA receptors.


Traumatic (type II) odontoid fracture with transverse atlantal ligament injury: a controversial event.
Traumatic (Type II) odontoid fractures are very common injuries. Nevertheless, their connection with transverse atlantal ligament injury is controversial and poorly defined. The aim of this study is to report a single case of traumatic (type II) odontoid fracture with transverse atlantal ligament injury and to critically analyze the role of ligaments and membranes together with neuroradiological tools in the management of craniovertebral junction-traumatized patients. We report 27 consecutive cases of traumatic (type II) odontoid fractures who underwent magnetic resonance imaging (MRI) in the acute phase injury (<72 hours), focusing our attention on the transverse atlantal ligament. One patient (3.7%) demonstrated a transverse atlantal ligament injury on MRI. The patient underwent surgery. Traumatic (type II) odontoid fracture with transverse atlantal ligament avulsion can be considered an unusual event. It is our opinion that the routine use of MRI for all patients with type II odontoid fracture could be unjustified in clinical practice. Strict clinical surveillance of all patients managed conservatively and the use of MRI in selected cases could be a reasonable management option.


Dysglycaemia in small-for-gestational-age neonates: a matched case-control study in monochorionic twins.
Small-for-gestational-age (SGA) neonates (birth weight <10th centile) are at higher risk of altered glucose homeostasis compared to appropriate for gestational age (AGA) neonates. The aim of this matched case-control study was to estimate the incidence of hypoglycaemia and/or hyperglycaemia in monochorionic (MC) twins with selective intrauterine growth restriction (sIUGR). We included all MC twins with sIUGR (2002-2013). Neonates in the SGA group were matched with their AGA co-twin. We recorded the occurrence of hypoglycaemia and hyperglycaemia in the first 48 h after birth and studied the association with SGA. In this retrospective study were 126 twin pairs included. The incidence of hypoglycaemia in the SGA group and AGA group was 29.6% and 17.4%, respectively, hyperglycaemia occurred in 8.7% of the SGA neonates and in 2.6% of the AGA co-twins. Multivariate analysis showed an independent association of SGA with hypoglycaemia (OR 1.97, CI 1.23-3.18, p ≤ 0.01), but not with hyperglycaemia (OR 2.57, CI 1.64-10.28, p = 0.182). Low gestational age (GA) at birth (OR 1.65, CI 1.09-2.48, p = 0.02) showed an independent association with hyperglycaemia. The risk of hypoglycaemia is almost twofold higher in SGA neonates compared to their MC AGA twins. Low GA appeared to be an independent risk factor for hyperglycaemia in SGA neonates.


Temporal discounting and smoking cessation: choice consistency predicts nicotine abstinence in treatment-seeking smokers.
Smokers discount delayed rewards steeper than non-smokers or ex-smokers, possibly due to neuropharmacological effects of tobacco on brain circuitry, or lower abstinence rates in smokers with steep discounting. To delineate both theories from each other, we tested if temporal discounting, choice inconsistency, and related brain activity in treatment-seeking smokers (1) are higher compared to non-smokers, (2) decrease after smoking cessation, and (3) predict relapse. At T1, 44 dependent smokers, 29 non-smokers, and 30 occasional smokers underwent fMRI while performing an intertemporal choice task. Smokers were measured before and 21 days after cessation if abstinent from nicotine. In total, 27 smokers, 28 non-smokers, and 29 occasional smokers were scanned again at T2. Discounting rate k and inconsistency var(k) were estimated with Bayesian analysis. First, k and var(k) in smokers in treatment were not higher than in non-smokers or occasional smokers. Second, neither k nor var(k) changed after smoking cessation. Third, k did not predict relapse, but high var(k) was associated with relapse during treatment and over 6 months. Brain activity in valuation and decision networks did not significantly differ between groups and conditions. Our data from treatment-seeking smokers do not support the pharmacological hypothesis of pronounced reversible changes in discounting behavior and brain activity, possibly due to limited power. Behavioral data rather suggest that differences between current and ex-smokers might be due to selection. The association of choice consistency and treatment outcome possibly links consistent intertemporal decisions to remaining abstinent.


Prandial subcutaneous injections of glucagon-like peptide-1 cause weight loss in obese human subjects.
Recombinant glucagon-like peptide-1 (7-36)amide (rGLP-1) was recently shown to cause significant weight loss in type 2 diabetics when administered for 6 weeks as a continuous subcutaneous infusion. The mechanisms responsible for the weight loss are not clarified. In the present study, rGLP-1 was given for 5 d by prandial subcutaneous injections (PSI) (76 nmol 30 min before meals, four times daily; a total of 302.4 nmol/24 h) or by continuous subcutaneous infusion (CSI) (12.7 nmol/h; a total of 304.8 nmol/24 h). This was performed in nineteen healthy obese subjects (mean age 44.2 (sem 2.5) years; BMI 39.0 (sem 1.2) kg/m(2)) in a prospective randomised, double-blind, placebo-controlled, cross-over study. Compared with the placebo, rGLP-1 administered as PSI and by CSI generated a 15 % reduction in mean food intake per meal (P=0.02) after 5 d treatment. A weight loss of 0.55 (sem 0.2) kg (P<0.05) was registered after 5 d with PSI of rGLP-1. Gastric emptying rate was reduced during both PSI (P<0.001) and CSI (P<0.05) treatment, but more rapidly and to a greater extent with PSI of rGLP-1. To conclude, a 5 d treatment of rGLP-1 at high doses by PSI, but not CSI, promptly slowed gastric emptying as a probable mechanism of action of increased satiety, decreased hunger and, hence, reduced food intake with an ensuing weight loss.


The PFAPA syndrome in oral medicine: differential diagnosis and treatment.
Periodic fever syndromes in children can present with orofacial manifestations which contribute to the formulation of a differential diagnosis. Because of the early onset of oral lesions in these syndromes, the oral medicine practitioner may be required to assist in their diagnosis and management. The periodic fever, aphthous stomatitis, pharyngitis and adenitis (PFAPA) syndrome has been classified as a type of periodic fever syndrome ocurring in early childhood. This article presents a review of the published literature on this entity and summarizes current therapeutic options.


Peptidoglycan induces nuclear factor-kappaB activation and cyclooxygenase-2 expression via Ras, Raf-1, and ERK in RAW 264.7 macrophages.
In this study, we investigated the signaling pathway involved in cyclooxygenase-2 (COX-2) expression caused by peptidoglycan (PGN), a cell wall component of the Gram-positive bacterium Staphylococcus aureus, in RAW 264.7 macrophages. PGN caused dose- and time-dependent increases in COX-2 expression, which was attenuated by a Ras inhibitor (manumycin A), a Raf-1 inhibitor (GW 5074), and an MEK inhibitor (PD 098059). Treatment of RAW 264.7 macrophages with PGN caused time-dependent activations of Ras, Raf-1, and ERK. The PGN-induced increase in Ras activity was inhibited by manumycin A. Raf-1 phosphorylation at Ser-338 by PGN was inhibited by manumycin A and GW 5074. The PGN-induced increase in ERK activity was inhibited by manumycin A, GW 5074, and PD 098059. Stimulation of cells with PGN activated IkappaB kinase alpha/beta (IKKalpha/beta), IkappaBalpha phosphorylation, IkappaBalpha degradation, and kappaB-luciferase activity. Treatment of macrophages with an NF-kappaB inhibitor (pyrrolidine dithiocarbamate), an IkappaBalpha phosphorylation inhibitor (Bay 117082), and IkappaB protease inhibitors (l-1-tosylamido-2-phenylethyl chloromethyl ketone and calpain inhibitor I) all inhibited PGN-induced COX-2 expression. The PGN-mediated increase in the activities of IKKalpha/beta and kappaB-luciferase were also inhibited by the Ras dominant negative mutant (RasN17), manumycin A, GW 5074, and PD 098059. Further studies revealed that PGN induced the recruitment of p85alpha and Ras to Toll-like receptor 2 in a time-dependent manner. Our data demonstrate for the first time that PGN activates the Ras/Raf-1/ERK pathway, which in turn initiates IKKalpha/beta and NF-kappaB activation, and ultimately induces COX-2 expression in RAW 264.7 macrophages.


Purification and characterization of a novel mycolic acid exchange enzyme from Mycobacterium smegmatis.
We have isolated and purified to homogeneity an alpha,alpha'-trehalose 6-monomycolate:alpha,alpha'-trehalose mycolyltransferase (trehalose mycolyltransferase) from Mycobacterium smegmatis that catalyzes the exchange of a mycolyl group between trehalose, trehalose 6-monomycolate (TM), and trehalose 6,6'-dimycolate (TD). This enzyme was prominent in M. smegmatis and it catalyzed the following reactions. TM + [14C]trehalose in equilibrium [14C]TM + trehalose [14C]TM + TM in equilibrium [14C]TD + trehalose This enzyme was purified by (i) ammonium sulfate fractionation, (ii) QAE-Sephadex A-50 column chromatography, (iii) gel filtration on a Sephadex G-75 column, and (iv) SP-Sephadex C-50 column chromatography. The purified protein yielded a single band on sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and its molecular weight was estimated to be 25,000. This enzyme was a glycoprotein, had no cofactor requirement, and was highly specific for alpha,alpha'-trehalose as the mycolate acceptor. It was less specific for the acyl donor group since the palmitoyl group in trehalose 6-monopalmitate was easily exchangeable. There was no TM acylhydrolase activity in the purified enzyme, suggesting that it is probably associated with the anabolic pathway of mycolic acid metabolism. We postulate the formation of a mycolyl-enzyme intermediate in this reaction. Such an intermediate could play a central role in the transfer of mycolic acid to form the prominent cell wall components of mycobacterial TD and possibly murein-arabinogalactan-mycolate.


Fowl cholera: immunization of chickens with potassium thiocyanate (KSCN) extract of Pasteurella multocida serotype 3.
Potassium thiocyanate (KSCN) extract of Pasteurella multocida, serotype 3, was found to be immunogenic against a challenge infection of homologous as well as one heterologous strain tested (serotype 1). Ouchterlony's gel-diffusion analysis revealed the presence of two components in the KSCN-extracts of both serotypes 3 and 1, which were antigenically identical.


Relationship between prostacyclin biosynthesis and cyclic AMP in cultured rabbit mesothelial cells.
Calcium ionophore A23187 (10 microM) as well as thrombin (10 U/ml) stimulated the biosynthesis of prostacyclin in cultured rabbit mesothelial cells; in the presence of the phosphodiesterase inhibitor isobutylmethylxanthine (Mix, 1 mM) the cyclic AMP (cAMP) content was also elevated. Both effects were inhibited by indomethacin (28 microM). Exogenous prostacyclin elicited by itself a clear enhancement of intracellular cAMP. An increased cAMP content was also obtained with isoproterenol (10 microM), whose activity was antagonized by propranolol (10 microM). These two products however, had no effect on the prostacyclin release. In all these experiments, inhibition of phosphodiesterase with Mix, was necessary to obtain detectable cAMP levels. In the presence of Mix, the stimulation of prostacyclin production by A23187 and thrombin was significantly lower as compared to the stimulation in the absence of Mix. Our results suggest that increased prostacyclin biosynthesis results in adenylate cyclase stimulation. This rise in intracellular cAMP in the presence of Mix, is accompanied by a downward regulation of further prostacyclin production.


Assessing the effect of the coal-to-gas program on air pollution: evidence from China.
This paper studies the relationship between the coal-to-gas program and air pollution in China and provides micro-evidence of the mechanism from the perspective of households. Using daily air pollution and meteorological data between January 1, 2016, and January 1, 2020, we assessed the effect of the coal-to-gas program on air pollution by introducing the regression discontinuity designs in time (RDiT). We found that the coal-to-gas program significantly improved air quality and brought significant economic benefits. In the short term, the coal-to-gas program can lead to more than 10 units of reduction in SO2, PM2.5, and AQI in the treatment group, while it can lead to more than 50 units in the long term. Using the difference-in-differences approach, we found that the coal-to-gas program has significantly reduced air pollution. Combined with the micro-panel data of the China Health and Retirement Longitudinal Study from 2011 to 2018, we found that the coal-to-gas program changes the household heating energy choices and that the probability of coal-fired heating of households in pilot areas is decreasing. The study suggests that non-clean energy in households should be further replaced to continue improving air quality.


Effect of supplementation of a basal diet of maize stover with Erythrina variegata, Gliricidia sepium or Leucaena leucocephala on feed intake and digestibility by goats.
Two 4 x 4 Latin square design experiments were carried out. In experiment 1, four mature Anglo-Nubian x Fiji local goats, pre-experimental body weight 25.0 +/- 0.6 kg, 22-24 months old, were used to study the effect of supplementation of a basal diet of maize stover with Erythrina variegata (EV), Gliricidia sepium (GS) and Leucaena leucocephala (LL) on dry matter intake (DMI) and nutrient digestibility. Maize stover treated with urea was used as a control diet. E. variegata was higher in crude protein content than LL or GS. The DMI of the urea treated stover diet was significantly lower (p < 0.05) than that of the diets of untreated stover supplemented with forage legumes. The DMI was significantly lower (p < 0.05) in the GS diet than in the EV or LL diets. Significant (p < 0.05) differences existed between the urea-treated stover and the diets of stover supplemented with forage legumes in the digestibility of dry matter (DM), crude protein (CP), neutral detergent fibre (NDF), organic matter (OM) and energy. In experiment 2, four mature goats, pre-experimental body weight 27.0 +/- 0.3 kg, 24-28 months old, were used to measure their response when the urea-treated maize stover and the maize stover and forage legume diets were sprayed with molasses. The intake of the urea-treated stover diet sprayed with molasses was significantly lower (p < 0.05) that that of the maize stover/forage legume diets sprayed with molasses. The DMI of the diets improved with the addition of molasses. The DMI among the goats offered the maize stover/forage legume diets + molasses did not differ significantly. (p > 0.05). Statistically significant (p < 0.05) differences were obtained in this second study between the urea-treated stover and the stover supplemented with forage legumes in the digestibility of DM, CP, NDF, OM and energy. The stover supplemented with forage legumes had a higher (p < 0.05) nutrient digestibility. The present studies demonstrated that the use of forage legumes as protein supplements improved the feed quality of maize stover in the diets of mature goats. It is suggested that molasses should be sprayed on fresh leaves of Gliricicia sepium and other forage legumes that are initially rejected, in order to improve acceptance and DMI when fed to ruminant animals in confinement or in a cut-and-carry system of production.


Is 2-dimensional transvaginal ultrasonography necessary 6 weeks after insertion of the levonorgestrel 52-mg intrauterine device?
In Dutch practice, gynecologists are used to assessing the position of the LNG-IUD by performing a two-dimensional transvaginal ultrasonography (TVUS) directly after insertion and do not routinely invite patients for another consultation 4-12 weeks after insertion. There is no consensus whether a TVUS six weeks after insertion is routinely needed. This study aimed to assess the incidence of malposition using 2-dimensional transvaginal ultrasonography during routine investigation 6 weeks after insertion. In addition, we investigated the relationship between malposition of the levonorgestrel 52-mg intrauterine device and unfavorable bleeding patterns and pelvic pain. We performed a large prospective cohort study. Patients seeking a levonorgestrel 52-mg intrauterine device were eligible for inclusion. Transvaginal ultrasonography was performed to check position of the levonorgestrel 52-mg intrauterine device immediately after insertion and 6 weeks later. Patients filled in questionnaires about bleeding pattern and pelvic pain 6 weeks after insertion. From March 2015 to December 2016, we enrolled 500 patients. Data from the transvaginal ultrasonography assessment 6 weeks after insertion were available for 448 patients, and complete data (transvaginal ultrasonography and questionnaire data) were available for 363 patients (72.6%). Malposition rate was 6.3% (28/448 patients). Malposition was seen in 15 of 198 patients (7.6%) with unfavorable bleeding and/or pelvic pain and in 3 of 165 patients (1.8%) with favorable bleeding patterns and no pelvic pain (P=.03).Malposition was seen in 14 of 186 patients (7.5%) with an unfavorable bleeding pattern and in 4 of 177 patients (2.3%) with favorable bleeding patterns (P=.008). Malposition was seen in 5 of 50 patients (10%) with pelvic pain and in 13 of 313 patients (4.2%) without pelvic pain (P=.08). The malposition rate of the levonorgestrel 52-mg intrauterine device observed using transvaginal ultrasonography 6 weeks after insertion was 6.3%. If patients have no complaints of unfavorable bleeding and/or pelvic pain, the risk for malposition is low (1.8%) and a routine transvaginal ultrasonography is not necessary. However, if patients experience unfavorable bleeding, a transvaginal ultrasonography should be considered to exclude malposition, because the effect of malposition on contraceptive effectiveness is unsure. Future research should focus on cost-benefit analysis.


Leaf biochemical parameters in Avicennia marina (Forsk.) Vierh as potential biomarkers of heavy metal stress in estuarine ecosystems.
Sediment loadings and leaf accumulation of the heavy metals copper (Cu), lead (Pb) and zinc (Zn) with accompanying changes in leaf chlorophylls' (a + b), carotenoids and the antioxidant enzyme peroxidase were examined in the grey mangrove Avicennia marina (Forsk.) Vierh, in order to determine the applicability of these parameters as biomarkers of heavy metal stress under field conditions. Copper was found to show limited accumulation to leaf tissue, following a linear relationship at lower sediment concentrations, with saturation at higher sediment Cu concentrations. Copper accumulation relationships to leaf tissue were maintained temporally, and increases in sediment Cu, salinity, and decreases in sediment pH and Zn contributed to the accumulation of Cu to leaf tissue. Lead showed a significant relationship between sediment and leaf Pb levels, but accumulation was minimal. Accumulation relationships for Pb were not maintained temporally, and high sediment Pb, low pH and organic content increased bioavailability and accumulation of Pb. Zinc was the most mobile of all metals and was accumulated to the greatest quantities in leaf tissue in a dose-dependant relationship. Some temporal variation in Zn accumulation occurred, and higher sediment pH, organic content Zn and Pb promoted leaf Zn accumulation. Leaf Cu and Zn showed the strongest relationship with peroxidase activity and to a lesser degree Pb. Zinc was the only accumulated metal to show relationship maintenance with peroxidase activity over time. It was found that peroxidase activity best reflects the total phytotoxic effect from the combined metal stress of all three accumulated leaf metals. The only significant photopigment relationship evidenced was that of leaf Zn with the chlorophyll a/b ratio, but was not maintained temporally. Peroxidase activity may be an appropriate biomarker for Zn or total metal accumulation in leaf tissue, and the chlorophyll a/b ratio a suitable biomarker of Zn accumulation though requires temporal monitoring under field conditions.


Elastic coupling of integral membrane protein stability to lipid bilayer forces.
It has been traditionally difficult to measure the thermodynamic stability of membrane proteins because fully reversible protocols for complete folding these proteins were not available. Knowledge of the thermodynamic stability of membrane proteins is desirable not only from a fundamental theoretical standpoint, but is also of enormous practical interest for the rational design of membrane proteins and for optimizing conditions for their structure determination by crystallography or NMR. Here, we describe the design of a fully reversible system to study equilibrium folding of the outer membrane protein A from Escherichia coli in lipid bilayers. Folding is shown to be two-state under appropriate conditions permitting data analysis with a classical folding model developed for soluble proteins. The resulting free energy and m value, i.e., a measure of cooperativity, of unfolding are DeltaG(u,H2O)(o)=3.4 kcal/mol and m = 1.1 kcal/mol M(-1), respectively, in a reference bilayer composed of palmitoyl-oleoyl-phosphatidylcholine (C(16:0)C(18:1)PC) and palmitoyloleoyl-phosphatidylglycerol (C(16:0)C(18:1)PG). These values are strong functions of the lipid bilayer environment. By systematic variation of lipid headgroup and chain composition, we show that elastic bilayer forces such as curvature stress and hydrophobic mismatch modulate the free energy and cooperativity of folding of this and perhaps many other membrane proteins.


Application of arthroscopic system in the treatment of lactational breast abscess.
Optimal treatment of breast abscesses has been controversial. Herein, we report an innovative method for the operative treatment of lactational mammary abscesses. Nineteen lactating patients diagnosed with breast abscesses were enrolled in the study, and abscess debridement and drainage were performed using an arthroscopic system. The clinical characteristics of the patients were recorded to evaluate the feasibility, efficacy, and cosmetic results of arthroscopic surgery for breast abscesses. All 19 patients were cured and did not relapse within the 6-month-follow-up period. One patient stopped breastfeeding due to breast leakage. All patients were satisfied with the postoperative appearance of the breast. Arthroscopic debridement and drainage are effective treatment methods for lactational breast abscesses, with a high cure rate, few complications, and satisfactory cosmetic outcomes.


Automated Sanger dideoxy sequencing reaction protocol.
The protocol for Sanger dideoxy chain termination reactions in DNA sequencing is tedious and prone to errors due to the repetitive character of the pipetting steps. An industrial robot, with the addition of a few simple parts, was programmed to automate the dideoxy sequencing reactions. The system is set up in a short time for routine operation and it is faster and more reliable than a human operator. It is flexible and allows variations and optimization of the standard procedure. Disposable microtiter plates at a controlled temperature are used. In one reaction cycle (about 50 min) up to 48 templates are processed. Up to 450 bases were resolved in automated DNA sequencing on samples prepared by the robot. The protocol is applicable to fluorescent as well as to radioactive labeling.


Frequency of cervical intraepithelial neoplasia and infectious agents for vaginitis in menstrual cycle phase.
The study objective was to verify differences in the diagnosis of infectious agents and CIN in cytological smears in the proliferative and secretory phases of the menstrual cycle. A retrospective study was carried out at the Federal University of "Triângulo Mineiro". Presence of Candida albicans, Trichomonas vaginalis, clue cells, Doderlein bacilli, cytolytic flora, coccoid bacillus, CIN and HPV were collected from the vaginal cytology tests, cervical and endocervical in healthy women of reproductive age from 1994 to 2004 (about 14,000 in total). The cytologies were divided into two groups: proliferative and secretory phase. Chi-square and Fisher's exact tests were used for statistical analysis with the significance level set at less than 0.05. The frequency of cytolysis and candidiasis was higher in the secretory phase of the menstrual cycle (p < 0.0001). When the presence of CIN associated with vulvovaginitis was evaluated, there was no significant difference in cytologies with CIN between the first and the second phases of the menstrual cycle. Frequency of the cytolytic flora and Candida albicans is influenced by the phase of the menstrual cycle, but CIN is not.


RecBC enzyme overproduction affects UV and gamma radiation survival of Deinococcus radiodurans.
Deinococcus radiodurans recovering from the effect of acute dose of gamma (gamma) radiation shows a biphasic mechanism of DNA double strands breaks repair that involves an efficient homologous recombination. However, it shows higher sensitivity to near-UV (NUV) than Escherichia coli and lacks RecBC, a DNA strand break (DSB) repair enzyme in some bacteria. Recombinant Deinococcus expressing the recBC genes of E. coli showed nearly three-fold improvements in near-UV tolerance and nearly 2 log cycle reductions in wild type gamma radiation resistance. RecBC over expression effect on radiation response of D. radiodurans was independent of indigenous RecD. Loss of gamma radiation tolerance was attributed to the enhanced rate of in vivo degradation of radiation damaged DNA and delayed kinetics of DSB repair during post-irradiation recovery. RecBC expressing cells of Deinococcus showed wild type response to Far-UV. These results suggest that the overproduction of RecBC competes with the indigenous mechanism of gamma radiation damaged DNA repair while it supports near-UV tolerance in D. radiodurans.


Evaluation of intern performance by medical inpatients.
Patients, as the recipients of medical care, have a unique and crucial perspective from which to judge the performance of physicians. In this study, 27 interns (postgraduate year 1 residents) were evaluated by a sample of 212 medical inpatients at two university-affiliated hospitals using a previously validated questionnaire constructed from patients' comments. Patients were generally very satisfied with the performance of their interns and valued traditional clinical skills and interpersonal skills equally. The most important and characteristic attributes of the interns as rated by patients were demonstrating personal concern, skill in treating disease, providing information about findings, preparation for impending events, availability, manner of communication, trust, and comforting and listening skills. Encouraging mutuality by the interns was not often done and was not believed to be particularly important by patients. Older patients and whites were more satisfied with their interns, whereas college-educated, employed, and male patients were less satisfied. Implications of the findings for understanding and teaching about the physician-patient relationship are discussed.


An exchange assay for the cytoplasmic glucocorticoid receptor in the liver of the rat.
Cytosolic receptor for glucocorticoids can exist in either the free or bound form; assays now in use measure only the free form. In order to assay the total glucocorticoid receptor content of rat liver, free plus bound, we have developed an exchange assay wherein specifically bound [3H]dexamethasone is shown to be a valid measure of receptor in the presence of high concentrations of corticosterone. The exchange between [3H]dexamethasone and corticosterone is able to proceed because, unter the conditions of the assay, corticosterone is almost completely metabolized.


Autologous matrix-induced chondrogenesis in osteochondral lesions of the talus.
Recurrent ankle sprains and other trauma as well as ankle malalignment can lead to chronic osteochondral lesions of the talus. Conservative treatment frequently fails. Several operative treatment techniques exist; however, the choice of the right procedure is difficult. This article presents a new surgical technique suitable for treatment osteochondral lesions that combines bone plasty and a collagen matrix.


Systemic prednisolone versus topical tranexamic acid for prevention of rebleeding in patients with traumatic hyphema: A randomized clinical trial.
To compare the efficacy of systemic prednisolone and topical tranexamic acid (TA) on the rate of rebleeding in patients with macroscopic traumatic hyphema (MTH). In a randomized clinical trial, patients with MTH were randomized to receive oral prednisolone (OP group) or topical TA drops (TA group). Comprehensive ophthalmic examinations including slit lamp examination and fundoscopy, intraocular pressure (IOP), best-corrected visual acuity (BCVA) and check for rebleeding were performed in all cases. Ninety eyes of 90 patients were included, and 45 patients were allocated into each group. Age, sex, IOP, BCVA and grade of hyphema were not different between groups. Rebleeding in the TA group (2 patients, 4.4%) occurred less frequently than in the OP group (7 patients, 15.6%), but this difference did not reach statistical significance (P=0.081). However, there was a significant difference between the two groups over time in terms of absorption of the MTH (P<0.001). Topical TA appears promising in the management of macroscopic traumatic hyphema.


Artificial intelligence enabled carbon capture: A review.
Carbon capturing is imperative to fight climate change as much carbon emissions are liberated into the atmosphere, leading to adversely negative environmental impacts. Today's world addresses all the issues with the aid of digital technologies like data pooling and artificial intelligence (AI). Accordingly, this study is articulated based on AI-assisted carbon capturing. Techniques including machine learning (ML), deep learning (DL), and hybrid techniques being adopted in carbon capture are discussed. The role of AI tools, frameworks, and mathematical models are also discussed herein. Furthermore, the confluence of AI in carbon capture patent landscape is explored. This study would allow researchers to envision the growth of AI-assisted carbon capture in mitigating climate change and meeting SDG 13 - climate action.


GAPO syndrome: three new Brazilian cases, additional osseous manifestations, and review of the literature.
The GAPO syndrome is an extremely rare autosomal recessive disease that presents as main characteristics evident growth retardation, alopecia, pseudoanodontia, progressive optic atrophy and a typical face. Until now, only 30 patients have been reported in the medical literature (nine of them from Brazil, including the three cases described in the present article). This study describes three siblings with GAPO syndrome, two female and one male, the children of consanguineous parents (first-degree cousins, inbreeding F = 1/16), who are older than the previously described patients, presenting the characteristic phenotype besides serious bone alterations in the lower limbs, which had not yet been observed.


Improving patient safety culture in general practice: an interview study.
When improving patient safety a positive safety culture is key. As little is known about improving patient safety culture in primary care, this study examined whether administering a culture questionnaire with or without a complementary workshop could be used as an intervention for improving safety culture. To gain insight into how two interventions affected patient safety culture in everyday practice. After conducting a randomised control trial of two interventions, this was a qualitative study conducted in 30 general practices to aid interpretation of the previous quantitative findings. Interviews were conducted at practice locations (n = 27) with 24 GPs and 24 practice nurses. The theory of communities of practice--in particular, its concepts of a domain, a community, and a practice--was used to interpret the findings by examining which elements were or were not present in the participating practices. Communal awareness of the problem was only raised after getting together and discussing patient safety. The combination of a questionnaire and workshop enhanced the interaction of team members and nourished team feelings. This shared experience also helped them to understand and develop tools and language for daily practice. In order for patient safety culture to improve, the safety culture questionnaire was more successful when accompanied by a practice workshop. Initial discussion and negotiation of shared goals during the workshop fuelled feelings of coherence and belonging to a community wishing to learn about enhancing patient safety. Team meetings and day-to-day interactions enhanced further liaison and sharing, making patient safety a common and conscious goal.


Corticotropin-induced changes in enzymatic activities of the post-pregnenolone steroidogenic pathway in rabbit adrenocortical cells.
In an attempt to delineate the effect of corticotropin (ACTH) on post-pregnenolone steroidogenesis, the activity of enzymatic systems operative in conversion of pregnenolone into glucocorticoids and androgens was studied in adrenocortical cells from control rabbits and from animals treated with ACTH for 12 days (ACTH 1-24, 200 micrograms s.c. daily). The cells from ACTH-treated rabbits exhibited an increased overall steroidogenic capacity and produced much more cortisol (P less than 0.0005) as well as other 17-hydroxylated steroids as a result of increased activity of 17 alpha-hydroxylase; corticosterone generation was concomitantly reduced. The increased conversion of pregnenolone or progesterone into androgens, as a result of previous treatment with ACTH, provides additional evidence for an effect of ACTH on 17 alpha-hydroxylase activity. A stimulatory effect of ACTH on 11 beta-hydroxylase was also evidenced by these cells, since conversion of 11-deoxycortisol into cortisol was enhanced (P less than 0.005). The increased production of androgens from 17-hydroxylated precursors by cells from ACTH-treated rabbits suggests that ACTH also exerts a prolonged stimulatory effect on 17,20-lyase. The activity of 3 beta-hydroxysteroid dehydrogenase-isomerase was apparently not influenced by chronic treatment with ACTH, judged from unchanged conversion of dehydroepiandrosterone into androstenedione. The activity of 11 beta-dehydrogenase was likewise unchanged in these conditions.


Clinical experiences with the use of an automated perimeter (Octopus) in the diagnosis and management of patients with glaucoma and neurologic diseases.
This is a study of 59 patients, 42 with glaucoma and 17 with neurological disease, to compare the Octopus automated perimeter with the conventional Goldmann and Tubinger perimeters for detection and assessment of visual field defects. We believe the Octopus automated perimeter is an excellent method for screening patients suspected of glaucoma and can be expected to identify over 90% of the patients actually having visual field loss due to glaucoma. In patients with neurological disease, the Goldmann perimeter was superior to either the Octopus or Tubinger perimeters in providing clinically useful information.


Role of imaging test with radionuclides in the diagnosis and treatment of pheochromocytomas and paragangliomas.
Radionuclide imaging tests with [123I] Metaiodobenzylguanidine (MIBG), [18F] -fluorodeoxyglucose, [18F]-fluorodopa, or 68Ga-DOTA(0)-Tyr(3)-octreotate are useful for the diagnosis, staging and follow-up of pheochromocytomas (PHEOs) and paragangliomas (PGLs) (PPGLs). In addition to their ability to detect and localize the disease, they allow a better molecular characterization of the tumours, which is useful for planning targeted therapy with iodine-131 (131I) -labelled MIBG or with peptide receptor radionuclide therapy (PRRT) with [177Lu]-labelled DOTATATE or other related agents in patients with metastatic disease. In this review we detail the main characteristics of the radiopharmaceuticals used in the functional study of PPGLs and the role of nuclear medicine tests for initial evaluation, staging, selection of patients for targeted molecular therapy, and radiation therapy planning. It also offers a series of practical recommendations regarding the functional imaging according to the different clinical and genetic scenarios in which PPGLs occur, and on the indications and efficacy of therapy with [131I]-MIBG and 177Lu-DOTATATE.


[Prevention of disorders of the blood acid-base equilibrium after operations on the stomach by prolonged pentamine ganglionic block].
The acid-base balance was studied in 70 patients operated for peptic ulcer. It was shown that during operation metabolic acidosis could develop and in the postoperative period there occurred metabolic alkalosis associated with hypokalemia. The continuous ganglionic blockade without a pentamine-induced hypotension performed by the proposed method was found to prevent shifts of the acid-base balance towards metabolic alkalosis in the postoperative period. The author believes that the favourable effect of the ganglionic blockade on the acid-base balance is related to the reduced hyperreaction of the sympathoadrenal system, adrenals to the operation trauma which prevents "stress" reactions of the patient.


DnaJA2 interacts with Japanese encephalitis virus NS3 via its C-terminal to promote viral infection.
Numerous studies have documented that the interaction of viral and cellular proteins is essential in the viral life cycle. In our previous study, to screen cellular proteins that take part in the life cycle of JEV, cellular proteins that interacted with JEV NS3 were identified by Co-immunoprecipitation coupled with mass spectrometry analysis (Co-IP-MS), the results showed that ILF2, DnaJA1, DnaJA2, CKB, TUFM, and PABPC1 that putatively interact with NS3. Another candidate protein, DnaJA2, which interacted with JEV NS3 protein, was selected for further study. Overexpression of DnaJA2 increased JEV infection. Conversely, the knockdown of DnaJA2 suppressed JEV infection. Furthermore, DnaJA2 interacted with NS5 besides NS3 and colocalized with viral dsRNA. Additionally, the level of viral NS3 protein expression was higher in cells overexpressing DnaJA2 than in cells with empty vector expression, whereas DnaJA2 knockdown resulted in NS3 protein degradation, which was subsequently restored by MG132 treatment. Further analysis revealed that the C-terminal of DnaJA2 was a critical domain for interaction with NS3 and promoted JEV infection. Collectively, our study identified DnaJA2 as an essential host factor required for JEV infection, potentially representing a novel therapeutic target for the development of antiviral therapies against JEV.


Aptamer-conjugated nanoparticles: preservation of targeting functionality demonstrated by microchip electrophoresis in frontal mode.
Aptamer-conjugated nanoparticles (Apt-NPs) are increasingly being developed for biomedical purposes and especially for diagnosis and therapy. However, there is no quantitative study of the targeting functionality of such grafted aptamers compared with free aptamers. Thus, we report the first determination of binding parameters for Apt-NP/target complexes, thanks to a continuous frontal analysis in a microchip electrophoresis format (named FACMCE), based on a methodology previously developed by our group. As a model system, the targeting ability of a lysozyme-binding aptamer conjugated to fluorescent maghemite nanoparticles was evaluated and showed evidence that the conjugation does not alter the affinity of this aptamer.


Pistachio Male Inflorescences as an Alternative Substrate for the Application of Atoxigenic Strains of Aspergillus flavus.
Aflatoxins are carcinogens mainly produced by Aspergillus flavus and A. parasiticus in susceptible crops, including pistachio. The primary inoculum sources of these pathogens are plant debris in the orchard soils. In Californian fields, one approach to controlling aflatoxin contamination is based on releasing the atoxigenic strain of A. flavus AF36 in inoculated (coated) sorghum grains (AF36 Prevail). However, this control method can fail due to poor sporulation of the AF36 strain or sorghum grain losses due to predation. In 2008 and 2018, we showed that toxigenic and atoxigenic isolates of Aspergillus spp. frequently colonized fallen inflorescences of male pistachio trees. Under controlled conditions, strain AF36 profusely colonized pistachio male inflorescences when humidity was higher than 90%. However, there were significant differences between types of inflorescence (aerial > fallen). In 2016, we considerably (P = 0.015) increased the population of AF36 on the canopies of trees when fallen inflorescences were inoculated with AF36, compared with untreated trees. In 2017 and 2018, these differences were not detected (P > 0.05) due to cross-contamination of strain AF36 between seasons and neighboring plots. In any case, the density of AF36 spores on the canopy of the inflorescence-treated trees was similar (P > 0.05) to that on trees treated with the commercial product. Here, we present a new method for applying strain AF36 based on using a natural, abundant, and uniformly distributed substrate in pistachio fields, and we discuss how it can be improved. Furthermore, our results indicate that, in pistachio orchards where biocontrol practices are not conducted, eliminating this important source of toxigenic Aspergillus inoculum is recommended.


Development and Characterization of Nano-Ink from Silicon Carbide/Multi-Walled Carbon Nanotubes/Synthesized Silver Nanoparticles for Non-Enzymatic Paraoxon Residuals Detection.
The ongoing advancement in the synthesis of new nanomaterials has accelerated the rapid development of non-enzymatic pesticide sensors based on electrochemical platforms. This study aims to develop and characterize Nano-ink for applying organophosphorus pesticides using paraoxon residue detection. Multi-walled carbon nanotubes, silicon carbide, and silver nanoparticles were used to create Nano-ink using a green synthesis process in 1:1:0, 1:1:0.5, and 1:1:1 ratios, respectively. These composites were combined with chitosan of varying molecular weights, which served as a stabilizing glue to keep the Nano-ink employed in a functioning electrode stable. By using X-ray powder diffraction, Raman spectroscopy, energy dispersive X-ray spectroscopy, and a field emission scanning electron microscope, researchers were able to examine the crystallinity, element composition, and surface morphology of Nano-ink. The performance of the proposed imprinted working electrode Nano-ink was investigated using cyclic voltammetry and differential pulse voltammetry techniques. The Cyclic voltammogram of Ag NPs/chitosan (medium, 50 mg) illustrated high current responses and favorable conditions of the Nano-ink modified electrode. Under the optimized conditions, the reduction currents of paraoxon using the DPV techniques demonstrated a linear reaction ranging between 0.001 and 1.0 µg/mL (R2 = 0.9959) with a limit of detection of 0.0038 µg/mL and a limit of quantitation of 0.011 µg/mL. It was concluded that the fabricated Nano-ink showed good electrochemical activity for non-enzymatic paraoxon sensing.


Laboratory diagnosis of boutonneuse fever by enzyme-linked immunosorbent assay.
Little is known about the use of the enzyme-linked immunosorbent assay (ELISA) in the diagnosis of boutonneuse fever, and the reports which do exist have concerned the use of a strain of African origin and a peroxidase-labelled conjugate. We have used, as antigen, a Sicilian strain of Rickettsia conorii recently isolated from a patient with boutonneuse fever and anti-human immunoglobulins G and M labelled with alkaline phosphatase as conjugate. 432 (84.6%) of 500 sera from patients with boutonneuse fever, 4.4% of 384 sera from patients with various other pathologies, and 2.9% of 204 sera from blood donors gave positive reactions. The ELISA was highly sensitive and specific in the diagnosis of boutonneuse fever, and seems to be the test of choice for sero-epidemiological investigations, and when a large number of specimens must be examined. The test is more sensitive than the indirect immunofluorescence test, at least in the early stage of the disease (44.9% vs 21.3% positive respectively), and a long time after an acute attack.


Neuronal target genes of the neuron-restrictive silencer factor in neurospheres derived from fetuses with Down's syndrome: a gene expression study.
Identification of genes and characterisation of their function is an essential step towards understanding complex pathophysiological abnormalities in Down's syndrome. We did a study to investigate abnormalities in gene expression in human neuronal stem cells and progenitor cells from Down's syndrome and control post-mortem human fetal tissue. Indexing-based differential display PCR was done on neuronal precursor cells derived from the cortex of a fetus with Down's syndrome, and findings were compared with those of two control samples. Findings were validated against neurosphere preparations from three independent Down's syndrome fetuses and five independent controls by real-time quantitative PCR. Results of differential display PCR analysis showed that SCG10--a neuron--specific growth-associated protein regulated by the neuron-restrictive silencer factor REST-was almost undetectable in the Down's syndrome sample. This finding was validated by real-time PCR. We also found that other genes regulated by the REST transcription factor were selectively repressed, whereas non-REST-regulated genes with similar functions were unaffected. Changes in expression of several key developmental genes in the Down's syndrome stem-cell and progenitor-cell pool correlated with striking changes in neuron morphology after differentiation. Our findings suggest a link between dysregulation of the REST transcription factor and some of the neurological deficits seen in Down's syndrome. Experimental REST downregulation has been shown to trigger apoptosis, which could account for the striking and selective loss of neurons in the differentiated Down's syndrome cell preparations.