Therapeutic Efficacy Assessment of CK6, a Monoclonal KIT Antibody, in a Panel of Gastrointestinal Stromal Tumor Xenograft Models.
We evaluated the efficacy of CK6, a KIT monoclonal antibody, in a panel of human gastrointestinal stromal tumor (GIST) xenograft models. Nude mice were bilaterally transplanted with human GIST xenografts (four patient derived and two cell line derived), treated for 3 weeks, and grouped as follows: control (untreated); CK6 (40 mg/kg, 3× weekly); imatinib (50 mg/kg, twice daily); sunitinib (40 mg/kg, once daily); imatinib + CK6; sunitinib + CK6 (same doses and schedules as in the single-agent treatments). Tumor volume assessment, Western blot analysis, and histopathology were used for evaluation of efficacy. Statistical analysis was performed using Mann-Whitney U (MWU) and Wilcoxon matched-pairs tests. CK6 as a single agent only reduced tumor growth rate in the UZLX-GIST3 model (P = .053, MWU compared to control), while in none of the other GIST models an effect on tumor growth rate was observed. CK6 did not result in significant anti-proliferative or pro-apoptotic effects in any of the GIST models, and moreover, CK6 did not induce a remarkable inhibition of KIT activation. Furthermore, no synergistic effect of combining CK6 with tyrosine kinase inhibitors (TKIs) was observed. Conversely, in certain GIST xenografts, anti-tumor effects seemed to be inferior under combination treatment compared to single-agent TKI treatment. In the GIST xenografts tested, the anti-tumor efficacy of CK6 was limited. No synergy was observed on combination of CK6 with TKIs in these GIST models. Our findings highlight the importance of using relevant in vivo human tumor xenograft models in the preclinical assessment of drug combination strategies.


Experimental and computational analysis of the secretome of the hyperthermophilic archaeon Pyrococcus furiosus.
Although Pyrococcus furiosus is one of the best studied hyperthermophilic archaea, to date no experimental investigation of the extent of protein secretion has been performed. We describe experimental verification of the extracellular proteome of P. furiosus grown on starch. LC-MS/MS-based analysis of culture supernatants led to the identification of 58 proteins. Fifteen of these proteins had a putative N-terminal signal peptide (SP), tagging the proteins for translocation across the membrane. The detected proteins with predicted SPs and known function were almost exclusively involved in important extracellular functions, like substrate degradation or transport. Most of the 43 proteins without predicted N-terminal signal sequences are known to have intracellular functions, mainly (70 %) related to intracellular metabolism. In silico analyses indicated that the genome of P. furiosus encodes 145 proteins with N-terminal SPs, including 21 putative lipoproteins and 17 with a class III peptide. From these we identified 15 (10 %; 7 SPI, 3 SPIII and 5 lipoproteins) under the specific growth conditions of this study. The putative lipoprotein signal peptides have a unique sequence motif, distinct from the motifs in bacteria and other archaeal orders.


Factors affecting dystocia and offspring vigour in different sheep genotypes.
Birth difficulty and poor lamb vigour are significant causes of perinatal lamb mortality. In this study we investigated whether sheep breeds differing in appearance, muscularity and selection history also had differences in dystocia and lamb vigour, and considered some of the factors that may contribute to the variation in these traits. Data were collected at birth from a total of 3252 lambs of two terminal sire breeds selected for lean growth (Suffolk [S], n=500 and Texel [T], n=1207), from a Hill breed (Scottish Blackface [B], n=610), which has been mainly selected for hardiness, and a crossbred (Mule×T [M], n=935) representing a maternal line. For each lamb the degree of assistance at delivery, lamb presentation, amount of assistance to achieve successful sucking, sex, litter size and birth weight were recorded. T lambs required the most, and B and M lambs the least assistance at birth, S lambs were intermediate (% lambs assisted: T=55.7, S=30.7, B=22.7, M=24.9, P<0.001). T and S lambs were equally likely to be malpresented at birth (29% of births) and more likely to be malpresented than B or M lambs (20%; P<0.001). In T and S breeds lambs requiring veterinary assistance at delivery were mainly heavy and singleton lambs, whereas in B and M breeds these were exclusively low birth weight lambs in multiple litters. Although heavier lambs needed greater birth assistance, T lambs were lighter than S and M lambs, but heavier than B lambs (birth weight (kg): S=4.66, M=4.56, T=4.32, B=3.67, P<0.001). S lambs were more likely to require assistance with sucking than other breeds, and T lambs also required more assistance than B or M lambs (% lambs assisted to suck: S=56.0, T=31.6, M=19.8, B=18.4, P<0.001). Heavier lambs were more likely to suck unaided than lighter lambs (P<0.001). The data suggest that the two terminal sire breeds, selected narrowly for greater productivity (muscle growth and conformation), are more likely to experience birth difficulty and poorer lamb vigour than the breed selected for hardiness, or the cross breed. Whether these effects arise as a consequence of genetic selection (e.g. for specific lamb conformation), or as a result of management practices to achieve selection goals (e.g. increased intervention at lambing) is unknown. Specific actions to improve birth difficulty and lamb vigour, such as including these traits in the selection index, would be beneficial in improving the welfare of ewes and lambs of the terminal sire breeds.


Acute appendicitis during pregnancy.
To analyze the diagnosis and surgical treatment of acute appendicitis during pregnancy. The records of 24 pregnant patients who underwent surgery with preliminary diagnosis of acute appendicitis between January 1990 and July 2000 were reviewed retrospectively. Between January 1990 and July 2000, there were 31,480 deliveries and the incidence of acute appendicitis was 1/1,312. Twenty patients had pathologically proven acute appendicitis (83.3%). Of the remaining 4 patients, one had hemorrhagic ovarian cyst, one had ovarian cyst rupture and in two cases no surgical pathology was diagnosed. Gestational stage at the diagnosis was first trimester in 7 patients, second trimester in 12 patients and third trimester in 5 patients. Five patients had abortions and premature delivery occurred in 2 patients. Diagnosis of acute appendicitis is difficult in pregnancy. Delay in diagnosis and surgery results in increase in complications. Emergency surgical intervention should be performed when acute appendicitis is suspected during pregnancy.


Population variability in thermal performance of pre-spawning adult Chinook salmon.
Climate change is causing large declines in many Pacific salmon populations. In particular, warm rivers are associated with high levels of premature mortality in migrating adults. The Fraser River watershed in British Columbia, Canada, supports some of the largest Chinook salmon (Oncorhynchus tshawytscha) runs in the world. However, the Fraser River is warming at a rate that threatens these populations at critical freshwater life stages. A growing body of literature suggests salmonids are locally adapted to their thermal migratory experience, and thus, population-specific thermal performance information can aid in management decisions. We compared the thermal performance of pre-spawning adult Chinook salmon from two populations, a coastal fall-run from the Chilliwack River (125 km cooler migration) and an interior summer-run from the Shuswap River (565 km warmer migration). We acutely exposed fish to temperatures reflecting current (12°C, 18°C) and future projected temperatures (21°C, 24°C) in the Fraser River and assessed survival, aerobic capacity (resting and maximum metabolic rates, absolute aerobic scope (AAS), muscle and ventricle citrate synthase), anaerobic capacity (muscle and ventricle lactate dehydrogenase) and recovery capacity (post-exercise metabolism, blood physiology, tissue lactate). Chilliwack Chinook salmon performed worse at high temperatures, indicated by elevated mortality, reduced breadth in AAS, enhanced plasma lactate and potassium levels and elevated tissue lactate concentrations compared with Shuswap Chinook salmon. At water temperatures exceeding the upper pejus temperatures (Tpejus, defined here as 80% of maximum AAS) of Chilliwack (18.7°C) and Shuswap (20.2°C) Chinook salmon populations, physiological performance will decline and affect migration and survival to spawn. Our results reveal population differences in pre-spawning Chinook salmon performance across scales of biological organization at ecologically relevant temperatures. Given the rapid warming of rivers, we show that it is critical to consider the intra-specific variation in thermal physiology to assist in the conservation and management of Pacific salmon.


GAS5 knockdown ameliorates apoptosis and inflammatory response by modulating miR-26b-5p/Smad1 axis in cerebral ischaemia/reperfusion injury.
Ischemic stroke (IS) caused by cerebral arterial embolism remains the leading cause of disability and death worldwide. Cerebral ischemia / reperfusion (CI / R) injury is one of the common complications of ischemic stroke. Growth arrest specific transcript 5 (GAS5) has been found to be abnormally expressed in various tumors. However, the role and potential molecular mechanisms of GAS5 in CI / R-induced injury remain unknown. This study established a CI / R injury model in vivo and in vitro. The results showed that the expression of GAS5 was increased in CI / R rats, while miR-26b-5p expression was decreased. Besides, knockdown of GAS5 by siRNA (si-GAS5) reversed CI / R-induced apoptosis and inflammatory responses. Notably, bioinformatics analysis indicated that GAS5 competitively adsorbed miR-26b-5p, and the relationship was further confirmed by pull-down assay. In addition, miR-26b-5p overexpression reversed CI / R-induced apoptosis and inflammatory responses, whereas low expression of miR-26b-5p had the opposite effect. Moreover, TargetScan assay predicted that drosophila mothers against decapentaplegic protein 1 (Smad1) was a target of miR-26b-5p, and miR-26b-5p overexpression inhibited Smad1 expression. Conversely, Smad1 overexpression reversed the inhibitory effect of miR-26b-5p on CI / R-induced apoptosis and inflammatory responses in rats. Collectively, these results indicate that GAS5 knockdown can improve apoptosis and inflammatory responses by modulating the miR-26b-5p / Smad1 axis in CI / R rats.


The home numeracy environment and children's math skills: The moderating role of parents' math anxiety.
Evidence suggests that parents' math anxiety moderates the association between parents' help in mathematics homework and first graders' mathematics skills. Understanding whether similar associations are evident in younger children, in regard to the home numeracy environment (HNE) is essential, given that early math skills are strong predictors of later academic outcomes, and children's skills prior to kindergarten are fostered principally by their parents. Thus, the purpose of this study was to examine the association and interaction between the HNE and parents' math anxiety related to preschool children's numeracy performance. Participants were 121 parent-child dyads. Results from hierarchical multiple regression models demonstrated that parents' math anxiety and the HNE, included as separate predictors of children's math skills, were not statistically significant. However, the interaction between HNE and parents' math anxiety was statistically significant, such that the positive association between HNE and children's numeracy skills emerged when parents felt less anxious about math. These findings highlight the importance of accounting for parents' math anxiety when exploring the home influences on children's numeracy skills.


A new technique of biliary reconstruction after "high hilar resection" of hilar cholangiocarcinoma with tumor extension to secondary and tertiary biliary radicals.
Radical operation for hilar cholangiocellular carcinoma, including extended hepatic resection, seems to improve prognosis by increasing the surgical curability rate. Nevertheless, high postoperative morbidity and mortality have been reported in patients with obstructive jaundice. We describe the technique of "high hilar resection" and a modification of bilioenteric anastomosis for drainage of the multiple secondary or tertiary biliary radicals. Ten patients with advanced hilar cholangiocellular carcinoma underwent a high hilar resection with complete parenchymal preservation, and the biliary drainage was reconstructed by a sheath-to-enteric hepaticojejunostomy. Because of the technical difficulty caused by anastomosis line in the range of the biliary sheath, a modification was performed by dividing the biliary apertures of segments 5 and 4b. A high hilar resection was successfully performed, and all patients were discharged from the hospital in good condition. No patient died postoperatively. The proximal resection margin was tumor-free in all patients. One patient died after 29 months of peritoneal carcinomatosis. None of the patients developed local recurrence around the hepaticojejunostomy. The remaining nine patients are alive after a mean follow-up of 28.8 months after surgery without any signs of recurrence. In highly selected patients with advanced hilar cholangiocellular carcinoma, a high hilar resection is technically safe and oncologically justifiable. In combination with our new technique of sheath-to-enteric anastomosis, the patients considerably benefit from the preservation of liver parenchyma with low postoperative morbidity and very short in-hospital stay.


Leveraging virtual reality to train certified nursing assistants as essential dementia-care personnel in the age of COVID-19.
COVID-19 has placed an extraordinary and disproportionate level of responsibility and risk on certified nursing assistants (CNAs) caring for persons with dementia (PWD) relative to their training, resources, and compensation levels. Nearly one-quarter of COVID-19 deaths in the United States have been nursing home residents and staff. Despite providing the majority of direct care, CNAs are amongst the most under-resourced and under-trained frontline workers. Given their essentiality, it is critical to support CNAs during the COVID-19 pandemic. The purpose of this work is to provide CNAs with a space to strengthen their knowledge and confidence in caring for PWD. This pilot study applies a virtual reality (VR) curriculum to train CNAs regarding the lived experiences of PWD and their loved ones. The VR vignette portrays a Latinx woman, Beatriz, through progressive stages of Alzheimer's disease. Chicago Methodist Senior Services (CMSS) CNAs were recruited (N=7; 86% female, 86% Black) for a seven-week online training program consisting of 1.5 hours per week. Each class included a didactic lecture and an Embodied Labs VR module depicting a first-person experience of dementia through a distributive model approach. The program concluded with two recorded focus groups. Participants completed the UCLA Geriatric Attitudes Scale, a dementia knowledge assessment, the Interpersonal Reactivity Index surveys, and a COVID-19 Impact questionnaire. Current analyses include qualitative content analysis for focus group data and descriptive, quantitative statistics for pre-and post-VR intervention surveys. Preliminary results demonstrate that CNAs endorsed a positive change in attitudes toward older adults (p=0.069), a deepened understanding of dementia, and increased confidence in caregiving skills. Focus groups allowed CNAs to discuss changes in resident behavior and support one another through a virtual platform during a global pandemic. Combining traditional didactic lectures with VR-based curricula provided CNAs with foundational knowledge and first-hand experience of dementia pathology. Participants reported greater levels of insight and empathy for PWD. Future aims include expansion of training content to include end-of-life conversations, LGBTQIA aging, and Lewy body dementia.


A multipurpose muscle ergometer.
A fast (0.1 mm steps within 2 ms), strong (40 N continuously) and accurate (resolution 0.002 N and 1.0 micron) muscle ergometer was developed to test dynamic and static properties of mammalian muscle. Both for twitches and for tetani isometric, isokinetic and isotonic contractions can be measured accurately. Force-velocity data and time to peak-force data of four EDL muscles, as well as force-extension data of their serial tendinous structures are shown to demonstrate the machine.


Cortisone induced alterations of costal cartilage in single and in parabiosed rats.
Cortisone-treated Buffalo rats have been parabiosed with untreated controls of the same age. The optical and electron microscopy, including histochemistry, of costal cartilage of these rats has been compared with that in single cortisone treated rats, single controls, and control parabiosed with control rats, at 14 and 28 days after parabiosis. Single cortisone-treated rats, in comparison to controls, have shown the greatest alteration in cellular morphology and in the extracellular matrix both at 14 and at 28 days. Cortisone-treated parabiosed rats demonstrate a gradation of these alterations. Cellular alterations include enhancement of lipid and glycogen deposition concrurently with the presence of numerous large cytoplasmic vacuoles containing beaded irregularly-shaped filaments, banded or unbanded collagen-like fibrils, and/or electron dense lamellar bodies. In the extracellular matrix, matrix vesicles, amianthoid fibers, randomly oriented unbanded fibrillar materials, and filament-like materials are most prominent in the single cortisone-treated rats and they are progressively less prominent in the cortisone-treated parabiosed rats, and in the parabiosed and single controls. Calcification of the extracellular matrix follows a similar pattern and is observed initially in pericellular halos of the single cortisone and in cortisone-treated rats parabiosed with controls. Histochemical techniques have shown that chondroitin sulfate is less demonstrable in the single cortisone and in the cortisone-treated parabiosed rats than it is in the single or parabiosed controls at 14 days but, at 28 days, all untreated or treated rats, single or parabiosed are basically comparable. Glycoproteins are prominent in the single cortisone-treated rats both at 14 and at 28 days and, at these same times, they are progressively less prominent in the cortisone-treated parabiosed rats and in the single or parabiosed controls. Many of the cortisone induced alterations in costal cartilage are suggestive of enhancement of the aging process.


Molecular and serological prevalence of Coxiella burnetii in bovine dairy herds in southern Chile: A PCR and ELISA-based assessment of bulk tank milk samples.
Coxiella burnetii (C. burnetii) is a highly resilient zoonotic bacterium responsible for Q fever, a disease which occurs worldwide, with the exception of New Zealand. However, in Chile, the prevalence and impact of C. burnetii in cattle herds remain poorly understood due to limited research. This study aimed to assess the presence of C. burnetii in dairy cattle herds in southern Chile, using two diagnostic methods on bulk tank milk samples. The results of the study revealed a high prevalence of C. burnetii infection in the analyzed herds. Of the 271 milk tank samples tested, 76% (208/271, CI: 71.1-81.5) tested positive using ELISA, while 73% (200/271, CI: 68.0-78.8) tested positive using qPCR. These findings indicate a significant presence of C. burnetii in the cattle herds studied. Despite the high prevalence observed, no new Q fever outbreaks have been reported in the study area. This discrepancy highlights the need for further research to better understand the transmission dynamics, environmental factors, and livestock management practices associated with C. burnetii infection. These studies will contribute to the development of effective prevention and control strategies and promote public health regarding Q fever.


Toxicological consequences of Aroclor 1254 ingestion by female rhesus (Macaca mulatta) monkeys. Part 1B. Prebreeding phase: clinical and analytical laboratory findings.
A group of 80 menstruating rhesus (Macaca mulatta) monkeys, with an average estimated age of 11.1 +/- 4.1 yr SD were first randomly allocated to four similar test rooms (20 monkeys/room), and then randomly allocated to one of five dose groups (four females/dose group/room). Each day, the monkeys self-ingested capsules containing doses of 0, 5, 20, 40 or 80 micrograms Aroclor 1254/kg body weight. After 25 months of daily dosing, approximately 90% of the treated females attained a qualitative pharmacokinetic steady state with respect to the concentration of polychlorinated biphenyl (PCB) in their adipose tissue. Subsequently, oestrogen and progesterone concentrations in serum were determined for one complete oestrous cycle and various immunological tests were conducted, while the monkeys continued to receive their daily dose of PCB. During the prebreeding phase of the study, blood for clinical and analytical monitoring including haematology, serum biochemistry, serum hydrocortisone, serum proteins (alpha 1, alpha 2, beta and gamma-globulins), serum immunoglobulins (A, G and M) and thyroid variables (thyroxine/triiodothyronine (T3) uptake ratio, percentage T3 uptake and free thyroxine index), were obtained monthly, as were specimens to ascertain the concentration of PCB in the blood, adipose tissue and faeces. Major findings among treated monkeys included the following: changes in haematology (decreased erythrocyte count, haematocrit, reticulocyte count, and mean platelet volume), serum biochemistry (decreased cholesterol and total bilirubin), immunotoxicity (decreased antibody production to sheep red blood cells and alterations in the percentage of T helper and T suppressor cells) and pathology (the number of regions of sebaceous gland lobules per unit of histological length was significantly reduced). These effects were observed at PCB doses lower than those previously reported for non-human primates.


A new 34-kilodalton isoform of human fibroblast growth factor 2 is cap dependently synthesized by using a non-AUG start codon and behaves as a survival factor.
Four isoforms of human fibroblast growth factor 2 (FGF-2) result from alternative initiations of translation at three CUG start codons and one AUG start codon. Here we characterize a new 34-kDa FGF-2 isoform whose expression is initiated at a fifth initiation codon. This 34-kDa FGF-2 was identified in HeLa cells by using an N-terminal directed antibody. Its initiation codon was identified by site-directed mutagenesis as being a CUG codon located at 86 nucleotides (nt) from the FGF-2 mRNA 5' end. Both in vitro translation and COS-7 cell transfection using bicistronic RNAs demonstrated that the 34-kDa FGF-2 was exclusively expressed in a cap-dependent manner. This contrasted with the expression of the other FGF-2 isoforms of 18, 22, 22.5, and 24 kDa, which is controlled by an internal ribosome entry site (IRES). Strikingly, expression of the other FGF-2 isoforms became partly cap dependent in vitro in the presence of the 5,823-nt-long 3' untranslated region of FGF-2 mRNA. Thus, the FGF-2 mRNA can be translated both by cap-dependent and IRES-driven mechanisms, the balance between these two mechanisms modulating the ratio of the different FGF-2 isoforms. The function of the new FGF-2 was also investigated. We found that the 34-kDa FGF-2, in contrast to the other isoforms, permitted NIH 3T3 cell survival in low-serum conditions. A new arginine-rich nuclear localization sequence (NLS) in the N-terminal region of the 34-kDa FGF-2 was characterized and found to be similar to the NLS of human immunodeficiency virus type 1 Rev protein. These data suggest that the function of the 34-kDa FGF-2 is mediated by nuclear targets.


Long-term outcomes of patients with acute coronary syndrome and nonobstructive coronary artery disease.
Patients with acute coronary syndrome (ACS) and nonobstructive coronary artery disease (CAD) have a substantial risk of subsequent coronary events within 1 year. The aim of the present study was to evaluate the prevalence, long-term outcomes, and adherence to oral antiplatelet therapy in patients with ACS and nonobstructive CAD compared with patients with ACS and obstructive CAD who had undergone percutaneous coronary intervention. Nonobstructive CAD was defined as an angiographic finding of <50% diameter stenosis in any major epicardial artery. These patients were further stratified into 2 groups: those with normal coronary arteries (0% angiographic stenosis) and those with mild CAD (0% to 50% angiographic stenosis). Major adverse cardiac events, defined as death, myocardial infarction, ACS leading to hospitalization, and nonfatal stroke, were recorded and compared with a historical control group of patients with ACS and obstructive CAD who had undergone percutaneous coronary intervention. Of 2,438 consecutive patients with ACS undergoing coronary angiography, 318 (13%) had nonobstructive CAD. Of the 318 with nonobstructive CAD, 160 had normal coronary arteries and 158 had mild CAD. Patients with obstructive CAD had experienced greater rates of major adverse cardiac events at 26 ± 16 months (16.6% vs 9.1%, p = 0.001), driven by a greater rate of myocardial infarction compared with those without (5.3% vs 0%, p <0.001). However, the rate of death, ACS leading to hospitalization, and stroke was similar. After adjusting for baseline characteristics, no difference was found in the risk of major adverse cardiac events across the groups. Only 50% of patients with nonobstructive CAD were prescribed dual antiplatelet therapy. In conclusion, patients with ACS and nonobstructive CAD remain at high risk of long-term recurrent ischemic events.


Synthesis of a novel multifunctional organic-inorganic nanocomposite for metal ions and organic dye removals.
In this study, we used solvent assisted mechano-synthesis strategies to form multifunctional organic-inorganic nanocomposites capable of removing both organic and inorganic contaminants. A zeolite X (Ze) and activated carbon (AC) composite was synthesized via state-of-the-art mechanical mixing in the presence of few drops of water to form Ze/AC. The second composite (Ze/L/AC) was synthesized in a similar fashion, however this composite had the addition of disodium terephthalate as a linker. Both materials, Ze/AC and Ze/L/AC, were characterized using scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDS), Powdered X-ray diffraction (P-XRD), Fourier-transform infrared spectrometry (FTIR), Accelerated Surface Area and Porosimetry System (ASAP), and thermal gravimetric analysis (TGA). The SEM-EDS displayed the surface structure and composition of each material. The sodium, oxygen and carbon contents increased after linker connected Ze and AC. The P-XRD confirmed the crystallinity of each material as well as the composites, while FTIR indicated the function groups (C=C, O-H) in Ze/L/AC. The contaminant adsorption experiments investigated the effects of pH, temperature, and ionic strength on the adsorption of methylene blue (MB) and Co(II) for each material. In MB adsorption, the first-order reaction rate of Ze/L/AC (0.02 h-1) was double that of Ze/AC (0.01 h-1). The reaction rate of Ze/L/AC (4.8 h-1) was also extraordinarily higher than that of Ze/AC (0.6 h-1) in the adsorption of Co(II). Ze/L/AC composite achieved a maximum adsorption capacity of 44.8 mg/g for MB and 66.6 mg/g for Co(II) ions. The MB adsorption of Ze/AC and Ze/L/AC was best fit in Freundlich model with R2 of 0.96 and 0.97, respectively, which indicated the multilayer adsorption. In the Co(II) adsorption, the data was highly fit in Langmuir model with R2 of 0.94 and 0.92 which indicated the monolayer adsorption. These results indicated both materials exhibited chemisorption. The activation energy of Ze/L/AC in MB adsorption (34.9 kJ mol-1) was higher than that of Ze/L/AC in Co (II) adsorption (26 kJ mol-1).


Estrogen-induced vitellogenin production by triploid coho salmon (Oncorhynchus kisutch), and its effect on plasma and pituitary gonadotropin.
Vitellogenin production was induced in immature diploid and triploid coho salmon by the weekly injection of 17 beta-estradiol at 1 mg/kg body wt. There was no significant difference between diploids and triploids for any of the results obtained, i.e., change in plasma vitellogenin and gonadotropin levels, hepatosomatic index, or pituitary gonadotropin content. Plasma vitellogenin levels were significantly higher in 17 beta-estradiol-treated fish than in sham-injected fish within a week of the first injection, and continued to rise with each subsequent injection. Plasma gonadotropin levels, on the other hand, were slightly (but significantly) depressed. The 17 beta-estradiol-treated fish had higher hepatosomatic indices and pituitary gonadotropin contents than sham-injected fish by 3 weeks after the first treatment. These data suggest that the occasional postmeiotic oocytes observed in triploids do not grow to full maturity due, in part, to an absent or diminished estrogen stimulus from the ovary on hepatic vitellogenin production.


Plasma-enhanced electrostatic precipitation of diesel exhaust particulates using nanosecond high voltage pulse discharge for mobile source emission control.
This study reports enhancement in the electrostatic precipitation (ESP) of diesel engine exhaust particulates using high voltage nanosecond pulse discharge in conjunction with a negative direct current (DC) bias voltage. The high voltage (20 kV) nanosecond pulses produce ion densities that are several orders of magnitude higher than those in the corona produced by a standard DC-only ESP. This plasma-enhanced electrostatic precipitator (PE-ESP) demonstrated 95 % remediation of PM and consumes less than 1 % of the engine power (i.e., 37 kW diesel engine at 75 % load). While the DC-only ESP remediation increases linearly with applied voltage, the plasma-enhanced ESP remains approximately constant over the applied range of negative DC biases. Numerical simulations of the PE-ESP process agree with the DC-only experimental results and enable us to verify the charge-based mechanism of enhancement provided by the nanosecond high voltage pulse plasma. Two different reactor configurations with different flow rates yielded the same remediation values despite one having half the flow rate of the other. This indicates that the reactor can be made even smaller without sacrificing performance. Here, this study finds that the plasma enhancement enables high remediation values at low DC voltages and smaller ESP reactors to be made with high remediation.


3-aminopyrazolopyrazine derivatives as spleen tyrosine kinase inhibitors.
Spleen tyrosine kinase is a new promising target for drug discovery to treat human cancer and inflammatory disorders. A series of pyrazolopyrazine-3-amine and pyrazolopyrimidine-3-amine derivatives was designed and synthesized as new spleen tyrosine kinase inhibitors. The efforts yielded compound 6h with promising spleen tyrosine kinase inhibition in both enzymatic and B-lymphoma cell proliferation assays. Additionally, compound 6h dose dependently inhibited the activation of spleen tyrosine kinase signal in human B-cell lymphoma cells. Compound 6h might serve as a lead for further development of new spleen tyrosine kinase inhibitors.


Experimental studies on the mechanism of action of timolol.
Timolol, which binds to beta-adrenergic receptors, is a potent antagonist of the catecholamine-stimulated synthesis of cyclic AMP. However, the actual mechanism of action by which timolol reduces intraocular pressure is not readily apparent. Compared to its efficacy in human eyes, the drug is relatively ineffective in rabbit eyes. A reasonable postulate is that soon after administration, timolol blocks endogenous adrenergic stimulation contributing to the formation of aqueous humor by the ciliary processes. Nevertheless, the long-lasting reduction of intraocular pressure persists at a time when the drug is no longer bound to beta-adrenergic receptors.


Perinatal outcome after selective feticide in monochorionic twin pregnancies.
To evaluate the incidence and risk factors of adverse perinatal outcome in complicated monochorionic twin pregnancies treated with selective feticide. This was a retrospective analysis of prospectively collected data from a consecutive, national cohort. All monochorionic twin pregnancies treated with selective feticide at Leiden University Medical Center between June 2000 and November 2011 were included. Obstetric and neonatal data were recorded. The primary outcome measure was adverse perinatal outcome, including fetal or neonatal demise or severe neonatal morbidity. Data on perinatal outcome were obtained in all cases (n = 131). Overall perinatal survival rate was 67.2% (88/131). Median gestational age at delivery was 34 (interquartile range, 23-38) weeks. Neonatal mortality and morbidity rate in liveborn children was 4.3% (4/92) and 12.0 % (11/92), respectively. Severe cerebral injury was detected in three children. The overall incidence of adverse perinatal outcome was 41.2% (54/131). Median gestational age at occurrence of preterm prelabor rupture of membranes (PPROM) was 19.0 weeks and 32.0 weeks in cases with and without adverse perinatal outcome, respectively (P = 0.017). Liveborn children with adverse perinatal outcome were born at a lower median gestational age (29.0 weeks) than were children without adverse perinatal outcome (38.0 weeks) (P < 0.001). The risk of adverse perinatal outcome after selective feticide is high and associated with low gestational age at occurrence of PPROM and low gestational age at delivery. Long-term follow-up to assess neurodevelopmental outcome in survivors is required.


A rapid method for the purification of supercoiled PM2 DNA by affinity chromatography on H1 histone covalently coupled to agarose.
A simple and rapid method is described for the purification of supercoiled PM2 DNA by affinity chromatography on columns of H1 histone covalently coupled to agarose. The method does not require the use of intercalating agents or ultracentrifugation procedures. Under the conditions most appropriate for purification, elution is carried out in a single step with buffered 0.7 M NaCl after the sample has been loaded onto the column in buffered 0.2 M NaCl. The DNA eluted at the higher salt concentration consists of supercoiled closed circular DNA at greater than 90% purity independently of the ratio of supercoiled to nicked circular DNA in the input mixture.


Successful simultaneous targeting of IgE and IL-5 in a severe asthmatic patient selected for lung transplantation.
We report a case of severe uncontrolled allergic and eosinophilic asthma in which omalizumab had led to a fast remission. After 18 months, mepolizumab was added to omalizumab because of increased blood eosinophils and a deterioration of asthma control. Asthma was then under control for the next 18 months. Discontinuation of mepolizumab in the ensuing 6 months led to a decrease in asthma control and an increased eosinophilia. The introduction of benralizumab resulted in an immediate increase of lung function, asthma control test (ACT), and symptom relief. Before the introduction of biologics, the patient was on the list for transplantation due to respiratory insufficiency. High-resolution CT scans before and after biologic therapy demonstrated a reduction of bronchial wall thickening and mucous plugging as well as an increase in bronchial caliber. The patient did therefore not need a transplant. We conclude that the dual use of biologics may be efficient in some cases of severe asthma.


Karyotypic evolution of a human undifferentiated large cell carcinoma of the lung in tissue culture.
Serial cytogenetic studies were performed on a cell line derived from a pleural effusion from a patient with undifferentiated large cell carcinoma of the lung. The initial sample had a broad range of chromosome numbers per cell, with a hypodiploid/pseudodiploid stem line and a hypotetraploid sideline. A sequence consisting of a doubling of chromosome number per cell followed by chromosome loss was observed repeatedly during 40 culture passages. The presence of metaphase spreads showing evidence of endoreduplication suggested this as a likely mechanism for the doubling of chromosome number per cell. Eleven marker chromosomes were observed in the cells of the primary sample; these markers persisted through all subsequent passages. Chromosomes 1, 2, 6, 7, 8, 11, and 16 were consistently overrepresented; each of these chromosomes was involved in marker formation. Chromosomes 4, 5, 9, 10, 19, 21, and 22 were consistently underrepresented. Every chromosome, either in its normal form and/or as part of a marker, was represented on the average by at least one copy per diploid cell. Eighteen new marker chromosomes were observed during the course of cell cultivation; one of these evolved into a clonal marker over the course of six cell passages. Of the new marker chromosomes that were formed during the observation period, the majority were found in hypotetraploid cells.


Epithelial cells respond to proteolytic and non-proteolytic detachment by enhancing interleukin-6 responses.
Intestinal inflammatory disease or infection often results in the loss of the epithelial layer as a result mainly of the action of proteases, including the leucocyte serine proteinases (neutrophil elastase), lysosomal cathepsins and the matrix metalloproteinases from recruited inflammatory cells. Previous studies have shown that bronchial or intestinal epithelial cells (IEC) can respond to proteolytic attack by producing cytokines. In this study, we have determined the effect of protease treatment on interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1) production by IEC lines. Both neutrophil elastase and trypsin treatment induced elevated levels of mRNA for IL-6 in rat IEC-6 cells. Non-proteolytic detachment of the IEC-6 cells also induced elevated levels of IL-6 mRNA, suggesting that the effect was not caused by a specific protease or degradation product, but probably by an effect on cell shape or cell detachment. Similar results were seen with the IEC-18 cell line. Trypsin treatment of the IEC-6 cells also enhanced unstimulated and IL-1 beta costimulated IL-6 secretion, but not MCP-1 secretion or mRNA levels. Finally, nuclear levels of the CCAAT/enhancer binding protein-beta (C/EBP-beta) were rapidly enhanced after proteolytic detachment of the IEC-6 cells, suggesting a mechanism for the enhancement of IL-6 mRNA responses. These data indicate that epithelial cells can respond to proteolytic attack or cell detachment by producing IL-6, a cytokine with several anti-inflammatory and antiprotease effects, which may be important in moderating the loss of the epithelial layer by its effects on nearby epithelial or inflammatory cells.


Larger prostatic adenomas in obese men with no associated increase in obstructive uropathy.
In 379 men less than age 75 years who underwent initial transurethral prostatectomy for benign prostatic hypertrophy specimen weights were compared with host ages, obesity, smoking habits and the presence of incidental cancer. Among 334 men 60 to 74 years old average specimen weights increased with increasing obesity from 20.3 to 36.6 gm. Underweight men in comparison with men at least 30% overweight demonstrated more small specimens (10 gm. or less, 24% versus 2%, p < 0.001) and fewer large specimens (50 gm. or more, 5% versus 26%, p < 0.005). This pattern was present in smokers and nonsmokers. Adenoma weights increased with increasing host age and were larger in nonsmokers of all age groups. Body habitus was similar in the prostatectomy patients and 290 office patients of similar age, suggesting no increase in obstructive uropathy among obese men despite the larger adenomas. These observations are compatible with different risk factors for the obstructing and nonobstructing components of benign prostatic enlargement.


Depolymerization reactions of hyaluronic acid in solution.
Samples of microbial sodium hyaluronate were degraded by heating, ultrasonication ultraviolet (UV) and gamma-ray irradiation and enzymatic treatment. The weight-average molecular weight, Mw, of hyaluronate in 0.15 M NaCl and 0.06 M Na2HPO4 was determined by gel filtration with UV detection. The Mw of the degraded samples varied from 8 x 10(4) to 1.38 x 10(6). Depolymerization processes can be described by linear relationship (1/Mw)2 = f(t) in the case of ultrasonic treatment and by non-linear relationships in the cases of heating and UV irradiation at 257 nm. Gamma-ray irradiation and enzymatic treatment caused chemical degradation and depolymerization to oligosaccharides, respectively.


Development and application of highly sensitive labeling reagents for amino acids.
Peptide natural products produced by microorganisms have attracted considerable attention as ideal drug leads owing to their low toxicity and high specificity toward target proteins compared with small-sized molecules. These peptide drug leads possess unusual structural features that endow them with unique biological activities and ideal physicochemical properties. In particular, these peptides often have d-amino acids, and therefore the absolute configuration of the component amino acids must be determined during the structural elucidation of newly isolated peptide drug leads. Recently, we developed highly sensitive labeling reagents FDVDA and FDLDA for the structural determination of the component amino acids in peptides. In an LC-MS-based structural study of peptides, these reagents enabled us to detect infinitesimal amounts of amino acids derived from mild degradation of the samples; we named this method the highly sensitive-advanced Marfey's method (HS-advanced Marfey's method). Herein, we first report the synthesis of these reagents and the LC-MS protocols for highly sensitive analyses of amino acids. Second, we discuss applications of the design concept. Specifically, two other labeling reagents were synthesized and their performance in terms of detection sensitivity was evaluated. These investigations provide insights on the structure-property relationship of these labeling reagents and therefore facilitate future on-demand structural modifications of the reagents to enhance their hydrophobicity, stability, and affinity for use with specialized HPLC columns. Finally, we demonstrated the effectiveness of our highly sensitive labeling reagents by using them to detect component amino acids in peptide natural products.


Viral surveillance and discovery.
The field of virus discovery has burgeoned with the advent of high throughput sequencing platforms and bioinformatics programs that enable rapid identification and molecular characterization of known and novel agents, investments in global microbial surveillance that include wildlife and domestic animals as well as humans, and recognition that viruses may be implicated in chronic as well as acute diseases. Here we review methods for viral surveillance and discovery, strategies and pitfalls in linking discoveries to disease, and identify opportunities for improvements in sequencing instrumentation and analysis, the use of social media and medical informatics that will further advance clinical medicine and public health.


A DFT study on reaction force approach of ammonia catalysed amide bond formation reaction between ammonia and formic acid.
A reaction force approach of ammonia catalysed stepwise amide bond formation between ammonia and formic acid is investigated using B3LYP/6-31G (d,p) level of density functional theory in gas phase. The stepwise amide bond formation mechanism involves two transition states, namely, TS1, in initial stage and TS2, in final stage of reaction pathway. The potential energy surfaces obtained from IRC calculations on transition state geometries are subjected to reaction force and reaction work calculations. The estimated reaction works of structural and electronic activities in the progress of reaction reflect the unfavorable formation of diol intermediate and preferential formation of formamide. While 91% of the activation energy comes from structural changes in preparative region of TS1 path, the structural and electronic rearrangements respectively, share 57.6% and 42.4% of total activation energy of TS2 pathway. The atomic resolution of IRC pathways and natural charge analysis reveal the importance of hydrogen atom of catalyst in TS1 path and the oxygen of water molecule in TS2 path in the progress of reaction.


The effects of thiol moiety of levamisole on both cellular and humoral immunity during the early response to a hapten-carrier complex.
Cell-mediated reactions to the carrier and antibody-mediated reactions to the hapten were studied in guinea-pigs treated with a single i.v. injection of the thiol moiety of levamisole (DTC), before or after immunization with a hapten-carrier complex. The results show that a heavy dose of DTC induced delayed hypersensitivity reactions to the carrier and decreased antibody synthesis to the hapten. On the other hand, with a small dose of DTC no delayed hypersensitivity could be induced, but antibody synthesis to the hapten was depressed or enhanced, depending upon whether the injection was done before or after immunization. The mechanisms whereby DTC modulated the immune response are discussed.


Biodegradation of Atrazine by Mixed Bacteria of Klebsiella variicola Strain FH-1 and Arthrobacter sp. NJ-1.
The purpose of this study is to enhance the biodegradability of atrazine with FH-1 and NJ-1 alone by selecting the mixing ratio, optimizing the culture medium and conditions. The results showed that FH-1 and NJ-1 have the best biodegradation effect on atrazine being mixed in a volume ratio of 3:2. In a single factor experiment, sucrose and NH4Cl provided carbon and nitrogen sources for the mixed bacteria. Subsequently, composition of fermentation medium was further optimized using Box-Behnken design of response surface methodology. Based on the results, growth of mixed bacteria and biodegradation of atrazine performed best effects with a biodegradation rate of 85.6% when sucrose and NH4Cl amounts were 35.30 g/L and 10.28 g/L. The optimal medium condition was 10% inoculum of mixed bacteria, with initial atrazine concentration of 50 mg/L, neutral or weakly alkaline pH value, 30°C. The biodegradation rate reached 97.4%, 11.8% higher than the unoptimized condition.


Caecal metastasis from breast cancer presenting as intestinal obstruction.
Gastrointestinal metastsasis from the breast cancer are rare. We report a patient who presented with intestinal obstruction due to solitary caecal metastasis from infiltrating ductal carcinoma of breast. We also review the available literature briefly. A 72 year old lady with past history of breast cancer presented with intestinal obstruction due to a caecal mass. She underwent an emergency right hemicolectomy. The histological examination of the right hemicolectomy specimen revealed an adenocarcinoma in caecum staining positive for Cytokeratin 7 and Carcinoembryonic antigen and negative for Cytokeratin 20, CDX2 and Estrogen receptor. Eight out of 11 mesenteric nodes showed tumour deposits. A histological diagnosis of metastatic breast carcinoma was given. To the best of our knowledge, this is the first case report of solitary metastasis to caecum from infiltrating ductal carcinoma of breast. Awareness of this possibility will aid in appropriate management of such patients.


New Furanone Derivatives and Alkaloids from the Co-Culture of Marine-Derived Fungi Aspergillus sclerotiorum and Penicillium citrinum.
Six new compounds including two furanone derivatives sclerotiorumins A and B (1 and 2), one novel oxadiazin derivative sclerotiorumin C (3), one pyrrole derivative 1-(4-benzyl-1H-pyrrol-3-yl)ethanone (4), and two complexes of neoaspergillic acid aluminiumneohydroxyaspergillin (5) and ferrineohydroxyaspergillin (6) were isolated from the co-culture of marine-derived fungi Aspergillus sclerotiorum and Penicillium citrinum. Compound 3 was the first natural 1,2,4-oxadiazin-6-one. Compound 5 showed significant and selective cytotoxicity against human histiocytic lymphoma U937 cell line (IC50 = 4.2 μm) and strong toxicity towards brine shrimp (LC50 = 6.1 μm), and oppositely increased the growth and biofilm formation of Staphylococcus aureus.


Electrochemical calibration of in vivo brain dialysis samplers.
Measurement of state-related changes in the concentration of an endogenous substance using the in vivo dialysis technique requires a definition of the factors which relate the concentration detected in the outflowing perfusate to the concentration actually occurring in the extracellular space in which the sampler is located. In determine these factors, a rapid and highly accurate detector system is required which measures the concentration recovery in the perfusate and the dead space of the entire sampling system. To reduce the limitations of the microdialysis technique, two electrochemical microcells were developed for calibration of dialysis probes by computerized voltammetry. The electrochemically calibrated samplers were implanted into freely moving cats to measure concentration changes of monoamine metabolites in synchrony with sleep stages identified by polygraphy in order to demonstrate the applicability of electrochemical calibration in dialysis methods used in behavioral investigations.


Cerebral blood flow changes after treatment of social phobia with the neurokinin-1 antagonist GR205171, citalopram, or placebo.
Evidence is accumulating that pharmacological blockade of the substance P preferring neurokinin-1 (NK1) receptor reduces anxiety. This study compared the effects of an NK1 receptor antagonist, citalopram, and placebo on brain activity and anxiety symptoms in social phobia. Thirty-six patients diagnosed with social phobia were treated for 6 weeks with the NK1 antagonist GR205171 (5 mg), citalopram (40 mg), or matching placebo under randomized double-blind conditions. GR205171 was administered for 4 weeks preceded by 2 weeks of placebo. Before and after treatment, regional cerebral blood flow (rCBF) during a stressful public speaking task was assessed using oxygen-15 positron emission tomography. Response rate was determined by the Clinical Global Impression Improvement Scale. Patients improved to a larger extent with the NK1 antagonist (41.7% responders) and citalopram (50% responders), compared with placebo (8.3% responders). Within- and between-group comparisons showed that symptom improvement was paralleled by a significantly reduced rCBF response to public speaking in the rhinal cortex, amygdala, and parahippocampal-hippocampal regions. The rCBF pattern was corroborated in follow-up analyses of responders and subjects showing large state anxiety reduction. Short-term administration of GR205171 and citalopram alleviated social anxiety. Neurokinin-1 antagonists may act like serotonin reuptake inhibitors by attenuating neural activity in a medial temporal lobe network.


Optimization, kinetics and antioxidant activity of exopolysaccharide produced from rhizosphere isolate, Pseudomonas fluorescens CrN6.
Pseudomonas fluorescens, isolated from rhizosphere soil, was exploited for the production of exopolysaccharide (EPS). A medium was constituted to enhance the yield of EPS. This study involved an agro waste as carbon substrate, rice bran, a replacement of glucose. Plackett-Burman statistical design was applied to evaluate the selected sixteen components from which, rice bran, peptone, NaCl and MnCl2 were found to be effective and significant on the fermentation process. To study the concentration of each component, central composite design was carried out and response surface plots indicated that the following concentrations significantly enhanced the production - rice bran 5.02%, peptone 0.35%, NaCl 0.51%, MnCl2 0.074%. Kinetic modeling was also performed to simulate the process parameters. Logistic model for microbial growth and Luedeking-Piret equation for product formation and substrate utilization were found to fit the experiment. The present investigation resulted in a maximum yield of 4.62g of EPS/L at 48h. High DPPH scavenging ability was a positive indication to use EPS as an antioxidant. The extracted polysaccharide could thus be ecofriendly due to its biodegradability and nontoxicity, and subjected to various industrial and pharmaceutical applications.


Geometrical analysis of human three-channel Lissajous' trajectory of auditory brain-stem evoked potentials.
Three-channel Lissajous' trajectories (3CLTs) of auditory brain-stem evoked potentials (ABEPs) were obtained for a group of 15 normal humans. 3CLTs were studied using geometric spatial descriptors of rate of bending (curvature), local planarity (torsion), as well as the parameters of best fit planes along the trajectory. Point-by-point analysis enabled objective determination of apices (curvature maxima) which divided the trajectory to curvilinear segments. Consecutive apices defined planar segments (each consisting of two curvilinear segments) along the trajectory. Of the two possibilities of arranging apices in the middle of planar segments only one yielded consistently planar segments. The alternative set of apex triads represented transitions between truly planar segments. The variability of position and orientation measures of planar segments was greater than that of apex latencies and plane limits. The significance of planes, as well as their generation, in 3CLT of ABEP, remains to be studied.


Poisoning mortality in Danish children and adolescents, 1970-2006 - a registry-based study.
To study poisoning mortality from birth to the end of teenage. Registry study within the Danish population including all deaths from poisoning in the 0-19-year age groups for the years 1970-2006. Poisoning mortality was age dependent with a modest peak in preschool children because of accidents and a very steep increase from 0.1/10(5) person years (p.y.) at 12 years to 6.1/10(5) p.y. at 19 years. Accidents, suicide and undetermined manner of death all contributed to the increase. A significant proportion of accidental and undetermined manner of death was caused by opioides and probably abuse related. During the study period, mortality decreased by more than 50% with all manners of death contributing significantly to the decline. Carbon monoxide poisoning was the overall dominating cause of death and contributed most to reduction in mortality. Poisoning death caused by opioides and unspecified drugs was unchanged over time. Poisoning mortality among the youngest Danish children was dominated by accidental poisonings. During teenage, the level and pattern of adults was approached with respect to suicidal and abuse related deaths. A fall in mortality since mid-eighties was explained by fewer deaths from carbon monoxide poisoning.


Postexercise blood pressure reduction in elderly hypertensive patients.
We sought to study: 1) the impact of hemodynamic and left ventricular function on short-term postexercise blood pressure reduction in elderly hypertensive patients; and 2) the 22-h postexercise effects on ambulatory blood pressure in elderly hypertensive patients. Although early exercise provokes postexercise blood pressure reduction, the mechanisms underlying this response are not completely understood. Besides, it is unclear whether the reduction in blood pressure after exercise lasts long enough to have clinical relevance in elderly hypertensive patients. We studied 24 elderly hypertensive patients (age 68.9 +/- 1.5 years) and 18 age-matched normotensive control subjects (age 68.1 +/- 1.2 years). Cardiac output (carbon dioxide rebreathing) and blood pressure (auscultatory) were measured at rest and after a 45-min period of low-intensity bicycle exercise (50% maximal oxygen uptake) and at 15, 30, 60 and 90 min after exercise. Left ventricular function (by Doppler echocardiography) was also evaluated. Ambulatory blood pressure monitoring was evaluated after 45 min of exercise or 45 min of rest, in a randomized order. In the hypertensive patients, exercise provoked a significant reduction in blood pressure, cardiac output, stroke volume and left ventricular end-diastolic volume. It also provoked a significant reduction in systolic, mean and diastolic blood pressure during a 22-h period, at daytime and nighttime. The short-term reduction in blood pressure after exercise in elderly hypertensive patients is associated with a decrease in stroke volume and left ventricular end-diastolic volume. The 22-h postexercise reduction in blood pressure demonstrates the clinical relevance of low-intensity exercise in elderly hypertensive patients.


Structural organization of the human complexin 2 gene (CPLX2) and aspects of its functional activity.
We report here on the in vitro and in silico characterization of the organization of the human complexin 2 (CPLX2) gene. This encodes for a protein of 134 amino acid residues, contains five exons, is localized on human chromosome 5q35.3, and spans more than 87 kb. We performed in silico analysis of the CPLX2 5' untranslated region (UTR) and propose an alternative variant of the gene transcript. Compared to the mRNA reported earlier [McMahon, H.T., Missler, M., Li, C., Sudhof, T.C., 1995. Complexins: cytosolic proteins that regulate SNAP receptor function. Cell 83, 111-119.], this transcript bears a partly altered 5'-UTR associated with the same open reading frame. Both CPLX2 transcripts share exons III-V; the alternative transcript is devoid of exons I and II, and includes exon A instead. Exon A is localized within CPLX2 intron 2 about 7 kb upstream to exon III. Using reverse transcription polymerase chain reaction (RT-PCR) we detected both types of transcripts in human brain mRNA. In silico data suggest that two putative alternative TATA-less promoter regions separated by 74 kb govern the expression of two CPLX2 transcripts. Several potential transcription start sites were detected by primer extension for each of two alternative CPLX2 transcripts. The relative abundance of the alternative transcripts was investigated in human and rat forebrain, cerebellum, and hippocampus. Whereas both transcripts were detected in human and rat brain, their expression levels were found to vary significantly among the regions investigated. The organization of CPLX2 transcripts is conserved in humans and rodents.


Hollow porous carbon nanospheres containing polar cobalt sulfide (Co9S8) nanocrystals as electrocatalytic interlayers for the reutilization of polysulfide in lithium-sulfur batteries.
The introduction of functional interlayers for efficient anchoring of lithium polysulfides has received significant attention worldwide. A facile wet-chemical method was adopted to obtain hollow porous carbon nanospheres (HPCNSs) impregnated with metallic and polar cobalt sulfide (Co9S8) nanocrystals (abbreviated as "Co9S8@HPCNS"). The prepared nanocrystals were employed as electrocatalytic interlayers via separator coating for the efficient capture and reutilization of polysulfide species in Li-S batteries. The HPCNSs were synthesized via the polymerization method followed by carbonization and template removal. The Co9S8 nanocrystals were impregnated inside the HPCNSs, followed by heat treatment in a reducing atmosphere. The porous structure of the CNS enables the efficient percolation of the electrolyte, in addition to accommodating unwanted volume fluctuations during redox processes. Furthermore, the metallic Co9S8 nanocrystals improve the electronic conductivity and enhance the polarity of the CNS towards the polysulfide. Correspondingly, the Li-S cells featuring Co9S8@HPCNS as electrocatalytic interlayers and regular sulfur (S) electrodes display improved electrochemical performance such as reasonable rate performance and prolonged cycling stability at different current rates (0.1, 0.5, and 1.0 C). Therefore, we anticipate that the rational design strategy proposed herein will provide significant insights into the synthesis of advanced materials for various energy storage applications.


Short-course radiotherapy in elderly patients with glioblastoma: feasibility and efficacy of results from a single centre.
The incidence of glioblastoma (GBM) in the elderly population is currently increasing, with a peak seen between 65 and 84 years. The optimal treatment in terms of both efficacy and quality of life still remains a relevant and debated issue today. The purpose of our study was to evaluate the feasibility of short-course hypofractionated accelerated radiotherapy (HART) in GBM patients aged over 70 years and with a good Karnofsky performance score (KPS). A review of medical records at the "Istituto Neurologico C. Besta" was undertaken; patients aged ≥ 70 years who had undergone adjuvant HART for GBM between January 2000 and January 2004 were included in the study. HART was administered to a total dose of 45 Gy, 2.5 Gy/fraction, in three daily fractions for three consecutive days/cycle fractions each, delivered in two cycles (split 15 days). A total of 33 patients were evaluable for the current analysis. Median follow-up was 10 months. According to CTCAE (version 3.0) criteria, none of the patients developed radiation-induced neurological status deterioration or necrosis. KPS evaluation after HART was found to be stable in 73 % of patients, improved in 24 %, and worse in 3 %. The median overall survival time of the entire study population was 8 months (range 2-24). Our findings suggest that a hypofractionated accelerated schedule can be a safe and effective option in the treatment of GBM in the elderly.


Clinical Effect of Early vs Late Amyloid Positron Emission Tomography in Memory Clinic Patients: The AMYPAD-DPMS Randomized Clinical Trial.
Amyloid positron emission tomography (PET) allows the direct assessment of amyloid deposition, one of the main hallmarks of Alzheimer disease. However, this technique is currently not widely reimbursed because of the lack of appropriately designed studies demonstrating its clinical effect. To assess the clinical effect of amyloid PET in memory clinic patients. The AMYPAD-DPMS is a prospective randomized clinical trial in 8 European memory clinics. Participants were allocated (using a minimization method) to 3 study groups based on the performance of amyloid PET: arm 1, early in the diagnostic workup (within 1 month); arm 2, late in the diagnostic workup (after a mean [SD] 8 [2] months); or arm 3, if and when the managing physician chose. Participants were patients with subjective cognitive decline plus (SCD+; SCD plus clinical features increasing the likelihood of preclinical Alzheimer disease), mild cognitive impairment (MCI), or dementia; they were assessed at baseline and after 3 months. Recruitment took place between April 16, 2018, and October 30, 2020. Data analysis was performed from July 2022 to January 2023. Amyloid PET. The main outcome was the difference between arm 1 and arm 2 in the proportion of participants receiving an etiological diagnosis with a very high confidence (ie, ≥90% on a 50%-100% visual numeric scale) after 3 months. A total of 844 participants were screened, and 840 were enrolled (291 in arm 1, 271 in arm 2, 278 in arm 3). Baseline and 3-month visit data were available for 272 participants in arm 1 and 260 in arm 2 (median [IQR] age: 71 [65-77] and 71 [65-77] years; 150/272 male [55%] and 135/260 male [52%]; 122/272 female [45%] and 125/260 female [48%]; median [IQR] education: 12 [10-15] and 13 [10-16] years, respectively). After 3 months, 109 of 272 participants (40%) in arm 1 had a diagnosis with very high confidence vs 30 of 260 (11%) in arm 2 (P < .001). This was consistent across cognitive stages (SCD+: 25/84 [30%] vs 5/78 [6%]; P < .001; MCI: 45/108 [42%] vs 9/102 [9%]; P < .001; dementia: 39/80 [49%] vs 16/80 [20%]; P < .001). In this study, early amyloid PET allowed memory clinic patients to receive an etiological diagnosis with very high confidence after only 3 months compared with patients who had not undergone amyloid PET. These findings support the implementation of amyloid PET early in the diagnostic workup of memory clinic patients. EudraCT Number: 2017-002527-21.


Assessment of the quality of different commercial providers using artificial intelligence for automated cephalometric analysis compared to human orthodontic experts.
The aim of this investigation was to evaluate the accuracy of various skeletal and dental cephalometric parameters as produced by different commercial providers that make use of artificial intelligence (AI)-assisted automated cephalometric analysis and to compare their quality to a gold standard established by orthodontic experts. Twelve experienced orthodontic examiners pinpointed 15 radiographic landmarks on a total of 50 cephalometric X‑rays. The landmarks were used to generate 9 parameters for orthodontic treatment planning. The "humans' gold standard" was defined by calculating the median value of all 12 human assessments for each parameter, which in turn served as reference values for comparisons with results given by four different commercial providers of automated cephalometric analyses (DentaliQ.ortho [CellmatiQ GmbH, Hamburg, Germany], WebCeph [AssembleCircle Corp, Seongnam-si, Korea], AudaxCeph [Audax d.o.o., Ljubljana, Slovenia], CephX [Orca Dental AI, Herzliya, Israel]). Repeated measures analysis of variances (ANOVAs) were calculated and Bland-Altman plots were generated for comparisons. The results of the repeated measures ANOVAs indicated significant differences between the commercial providers' predictions and the humans' gold standard for all nine investigated parameters. However, the pairwise comparisons also demonstrate that there were major differences among the four commercial providers. While there were no significant mean differences between the values of DentaliQ.ortho and the humans' gold standard, the predictions of AudaxCeph showed significant deviations in seven out of nine parameters. Also, the Bland-Altman plots demonstrate that a reduced precision of AI predictions must be expected especially for values attributed to the inclination of the incisors. Fully automated cephalometric analyses are promising in terms of timesaving and avoidance of individual human errors. At present, however, they should only be used under supervision of experienced clinicians.


"Trust Me, I'm a Scientist": How Philosophy of Science Can Help Explain Why Science Deserves Primacy in Dealing with Societal Problems.
Modern democratic societies tend to appeal to the authority of science when dealing with important challenges and solving their problems. Nevertheless, distrust in science remains widespread among the public, and, as a result, scientific voices are often ignored or discarded in favour of other perspectives. Though superficially "democratic", such a demotion of science in fact hinders democratic societies in effectively tackling their problems. Worryingly, some philosophers have provided ammunition to this distrust and scepticism of science. They either portray science as an institution that has unrightfully seized political power, or they claim that science constitutes only one voice among many and that scientists should know their proper place in our societies. As philosophers of science, we believe that it is potentially dangerous to undermine trust in science in this way. Instead, we believe that philosophers should help people to understand why science, even though it is far from perfect, deserves our trust and its special standing in modern societies. In this paper, we outline what such an explanation may look like from a naturalistic and pragmatic perspective, and we discuss the implications for the role of philosophy of science in science education.


Diagnosis of mycobacterial infections in the exotic pet patient with emphasis on birds.
The term "mycobacteriosis" encompasses a variety of infectious diseases of animals caused by bacteria of the genus Mycobacterium, which are chronic and debilitating diseases. More than 35 Mycobacterium spp can cause mycobacteriosis. The wide range of possible clinical signs and physical exam findings can make the antemortem diagnosis inconsistent and challenging. Proper sample collection and test modality in relation to the state of the disease process are essential. Clinicians can determine a presumptive diagnosis of mycobacteriosis, but the definitive etiologic diagnosis of mycobacteriosis relies on the correct identification of the mycobacteria through microbiological and molecular diagnostic methods.


Extending the linker region increases the activity of the Bacillus subtilis cellulase CelI15.
To investigate the effect of the linker region (LR) on the enzymatic activity, stability, and flexibility of Bacillus subtilis cellulase CelI15, six mutants were constructed that contained increasing numbers of the LR. The CelI15 mutant with three copies of the LR (approx. 57 amino acids) showed the highest activity, which was almost 20 % greater than that of wild type CelI15. The stability of the mutant enzymes increased as the copy number of the LR decreased. However, the substrate affinity of the mutant enzymes increased as the LR copy number increased, and the mutant with four copies of the LR exhibited the highest substrate affinity. Additionally, the flexibility of the CelI15 mutants increased as the LR copy number increased from zero to four copies, although it decreased sharply for the mutant with five copies of the LR. The activity of CelI15 was increased by increasing the LR copy number, which could be a potential way to improve its enzymatic properties.


Diagnostic value of monoclonal antibody B72.3 in detecting adenocarcinoma cells in serous effusions.
In serous effusions, the cytologic diagnosis of adenocarcinoma, and its distinction from mesothelial hyperplasia and malignant mesothelioma, is still difficult. This study compares the immunoreactivity of antibody B72.3 with that of anti-CEA, anti-LeuM1-antigen and anti-keratins in 41 serous effusions from patients with different malignant disorders. B72.3 selectively stained adenocarcinoma cells in 80% of the cases and was as good as anti-CEA and superior to anti-LeuM1-antigen and anti-keratins. It is concluded that B72.3 forms a useful supplement to conventional cytomorphology in the distinction between adenocarcinoma cells, reactive mesothelial cells and malignant mesothelial cells in serous effusions.


Health risk estimates for groundwater and soil contamination in the Slovak Republic: a convenient tool for identification and mapping of risk areas.
We undertook a quantitative estimation of health risks to residents living in the Slovak Republic and exposed to contaminated groundwater (ingestion by adult population) and/or soils (ingestion by adult and child population). Potential risk areas were mapped to give a visual presentation at basic administrative units of the country (municipalities, districts, regions) for easy discussion with policy and decision-makers. The health risk estimates were calculated by US EPA methods, applying threshold values for chronic risk and non-threshold values for cancer risk. The potential health risk was evaluated for As, Ba, Cd, Cu, F, Hg, Mn, NO3 (-), Pb, Sb, Se and Zn for groundwater and As, B, Ba, Be, Cd, Cu, F, Hg, Mn, Mo, Ni, Pb, Sb, Se and Zn for soils. An increased health risk was identified mainly in historical mining areas highly contaminated by geogenic-anthropogenic sources (ore deposit occurrence, mining, metallurgy). Arsenic and antimony were the most significant elements in relation to health risks from groundwater and soil contamination in the Slovak Republic contributing a significant part of total chronic risk levels. Health risk estimation for soil contamination has highlighted the significance of exposure through soil ingestion in children. Increased cancer risks from groundwater and soil contamination by arsenic were noted in several municipalities and districts throughout the country in areas with significantly high arsenic levels in the environment. This approach to health risk estimations and visualization represents a fast, clear and convenient tool for delineation of risk areas at national and local levels.


Litarcturus kexueiae sp. nov., a new deep-sea isopod from the Okinawa Trough (Crustacea, Isopoda, Valvifera, Antarcturidae).
A new species of the genus Litarcturus Brandt, 1990, L. kexueiae sp. nov., collected from deep sea of the Okinawa Trough, is described and illustrated. It is readily distinguished from the other seven species of the genus by bearing long supraocular spines about as long as the head and posterolateral pleotelsonic spines overreaching the pleotelson apex.


Fatal car trunk entrapment involving children--United States, 1987-1998.
During July-August 1998, at least 11 U.S. children died in three separate incidents of car trunk entrapment. This report summarizes these three incidents, describes characteristics of car trunk entrapment incidents involving children since 1987, and reviews measures to prevent children from becoming trapped in car trunks. The findings indicate that at least nine incidents of fatal car trunk entrapment involving children occurred during 1987-1998, that all incidents occurred in hot weather and involved children aged < or =6 years, and that these deaths were preventable.


Pro- and anti-inflammatory cytokine balance in major depression: effect of sertraline therapy.
The specific associations between antidepressant treatment and alterations in the levels of cytokines remain to be elucidated. In this study, we aimed to explore the role of IL-2, IL-4, IL-12, TNF-alpha, TGF-beta1, and MCP-1 in major depression and to investigate the effects of sertraline therapy. Cytokine and chemokine levels were measured at the time of admission and 8 weeks after sertraline treatment. Our results suggest that the proinflammatory cytokines (IL-2, IL-12, and TNF-alpha) and MCP-1 were significantly higher, whereas anti-inflammatory cytokines IL-4 and TGF-beta1 were significantly lower in patients with major depression than those of healthy controls. It seems likely that the sertraline therapy might have exerted immunomodulatory effects through a decrease in the proinflammatory cytokine IL-12 and an increase in the anti-inflammatory cytokines IL-4 and TGF-beta1. In conclusion, our results indicate that Th1-, Th2-, and Th3-type cytokines are altered in the depressed patients and some of them might have been corrected by sertraline treatment.


Comparative analysis of background EEG activity based on MRI findings in neonatal hypoxic-ischemic encephalopathy: a standardized, low-resolution, brain electromagnetic tomography (sLORETA) study.
It is important to assess the degree of brain injury and predict long-term outcomes in neonates diagnosed with hypoxic-ischemic encephalopathy (HIE). However, routine studies, including magnetic resonance imaging (MRI) and conventional encephalography (EEG) or amplitude-integrated EEG (aEEG), have their own limitations in terms of availability and accuracy of evaluation. Recently, quantitative EEG (qEEG) has been shown to improve the predictive reliability of neonatal HIE and has been further refined with brain mapping techniques. We investigated background EEG activities in 29 neonates with HIE who experienced therapeutic hypothermia, via qEEG using a distributed source model. MRI images were evaluated and classified into two groups (normal-to-mild injury vs moderate-to-severe injury), based on a scoring system. Non-parametric statistical analysis using standardized low-resolution brain electromagnetic tomography was performed to compare the current density distribution of four frequency bands (delta, theta, alpha, and beta) between the two groups. Electrical neuronal activities were significantly lower in the moderate-to-severe injury group compared with the normal-to-mild injury group. Background EEG activities in moderate-to-severe HIE were most significantly reduced in the temporal and parietal lobes. Quantitative EEG also revealed a decrease in background activity at all frequency bands, with a maximum in decrease in the delta component. The maximum difference in current density was found in the inferior parietal lobule of the right parietal lobe for the delta frequency band. Our study demonstrated quantitative and topographical changes in EEG in moderate-to-severe neonatal HIE. They also suggest possible implementation and evaluation of conventional EEG and aEEG in neonatal HIE. The findings have implications as biomarkers in the assessment of neonatal HIE.


Clarification of Safe Delivery by Iranian Experts Based on Clinical Governance: A Qualitative Study.
To clarify the principles of a safe delivery based on Clinical Governance Criteria, as recommended by the pertinent experts. The current study was part of a qualitative research conducted by content analysis method in 2013 and purposive sampling, performing 24 in-depth interviews based on semi-structured questions and analyzed using thematic content analysis. The participants in this research included midwives, obstetricians, managers, and hospital doctors. The data were under continuous consideration and comparative analysis in order to achieve data saturation. The main concepts derived from interpretations of the pertinent experts include: Patient & Public involvement; Risk Management; Education; Clinical efficiency; Clinical audit; Personnel & Management. In a safe delivery, there is a vicious cycle of causes the elimination of which is only possible through benchmarking patterns that attend to most aspects of a safe delivery. Changes to services require utilization of appropriate change management strategies.


Validation of the Basic Psychological Needs in Exercise Scale in a Portuguese sample.
In line with self-determination theory (SDT: Deci & Ryan, 1985, 2002) the satisfaction of the basic psychological needs for autonomy, competence, and relatedness has been identified as an important predictor of behavior and optimal functioning in various contexts including exercise. The lack of a valid and reliable instrument to assess the extent to which these needs are fulfilled among Portuguese exercise participants limits the evaluation of causal links proposed by SDT in the Portuguese exercise context. The aim of the present study was to translate into Portuguese and validate the Basic Psychological Needs in Exercise Scale (BPNES: Vlachopoulos & Michailidou, 2006). Using data from 522 exercise participants the findings provided evidence of strong internal consistency of the translated BPNES subscales while confirmatory factor analysis supported a good fit of the correlated 3-factor model to the data. The present findings support the use of the translated into Portuguese BPNES to assess the extent of basic psychological need fulfilment among Portuguese exercise participants.


A final adjustment for staff allocation under environmental uncertainty.
Through understanding the relationships between the previous day's (Sunday) demand and the remaining days' demand, a prediction model can be constructed. The staff level can be determined based on this prediction model. This model can also be applied in different hospital units or a staff environment other than hospitals.


The reification of the "pathological" gambler: an analysis of gambling treatment and the application of the medical model to problem gambling.
Is the medical model used to reify "pathological" gambling? A qualitative field study of 12 subjects with the diagnosis "pathological" gambler. None of the 12 subjects being treated for "pathological" gambling fit neatly in the category of "pathological" gambler. An examination of the treatment center revealed institutional grounds for the use of this diagnosis. Rather than a medical diagnosis, "pathological" gambling is a socially constructed phenomenon. Using the medical model serves clients interpersonally and clinicians occupationally.


Ursodeoxycholate increases cytosolic calcium concentration and activates Cl- currents in a biliary cell line.
Ursodeoxycholate (UDC) stimulates a bicarbonate-rich choleresis, but the cellular mechanisms involved are not fully established. Because ductular secretion also increases biliary HCO3-concentration, the purpose of this study was to evaluate whether UDC has direct effects on duct cells by measuring intracellular calcium concentration ([Ca2+]i) and membrane Cl- permeability in Mz-ChA-1 human cholangiocarcinoma cells. Intracellular calcium levels were measured using fura-2 fluorescence. Membrane Cl- permeability was assessed in subconfluent monolayers using 125I efflux and in individuals cells using whole-cell patch clamp techniques. Exposure to UDC (2.5 mmol/L) increased [Ca2+]i from 180 +/- 25 to 639 +/- 84 nmol/L due to release of Ca2+ from intracellular stores and stimulated 125I efflux approximately threefold above basal levels. Exposure to extracellular (1.25 mmol/L) or intracellular (100 mumol/L) UDC activated currents carried by Cl- ions; intracellular UDC increased current density from 4.7 +/- 1.3 to 32.5 +/- 8.8 pA/pF. UDC-stimulated currents were inhibited by chelation of intracellular calcium. UDC in pharmacological concentrations increases [Ca2+]i and stimulates Cl- efflux through opening of Cl- channels in biliary cells. We speculate that UDC could increase bile flow by direct stimulation of ductular secretion and may be of therapeutic benefit to patients with cystic fibrosis who have impaired adenosine 3',5'-cyclic monophosphate-dependent biliary secretion.


Perinatal hypothyroidism effects on neuromotor competence, novelty-directed exploratory and anxiety-related behaviour and learning in rats.
Thyroid hormone is essential for proper development of the mammalian CNS. Previous studies have documented a decrease in the ability of neonatal hypothyroid animals to learn and to habituate to maze tests and an increase in spontaneous activity. However, there is little information about the effects of perinatal (i.e. perinatal and postnatal) hypothyroidism on behaviour. The aim of the present work was to investigate the longitudinal effects of perinatal hypothyroidism on certain aspects of the behaviour in rats. Neuromotor competence was tested at 21, 40 and 60 days, novelty-directed exploratory behaviour and anxiety-related behaviour were evaluated at 40 and 60 days by means of the Boissier tests and associative learning ability was tested at 80 days by means of a step-through passive avoidance task. The persistence of the effects of perinatal hypothyroidism on psychomotor performance was highly dependent on the task examined. Perinatal hypothyroidism caused an increase of locomotor activity as revealed by the total distance travelled in the Boissier test and this increase also comprised a component of decreased anxiety-related behaviour. Methimazole-treated subjects also had higher head-dip scores than controls at 40 days while no differences were observed at 60 days. Finally, our results showed that methimazole-treated rats performed poorly in a passive avoidance learning task.


ANXA6/TRPV2 axis promotes lymphatic metastasis in head and neck squamous cell carcinoma by inducing autophagy.
Head and neck squamous cell carcinoma (HNSCC) is highly aggressive with a significant tropism of lymph nodes, which restricts treatment options and negatively impacts patient outcomes. Although progress has been made in understanding the molecular mechanisms underlying lymphatic metastasis (LM), these mechanisms remain elusive. ANXA6 is a scaffold protein that participates in tumor pathogenesis and autophagy regulation; however, how ANXA6 affects autophagy and LM in HNSCC cells remains unknown. RNA sequencing was performed on HNSCC clinical specimens with or without metastasis as well as on The Cancer Genome Atlas dataset to investigate ANXA6 expression and survival. Both in vitro and in vivo studies were performed to investigate the role of ANXA6 in the regulation of LM in HNSCC. The molecular mechanism by which ANXA6 interacts with TRPV2 was examined at the molecular level. ANXA6 expression was significantly upregulated in HNSCC patients with LM and higher expression was associated with poor prognosis. ANXA6 overexpression promoted the proliferation and mobility of FaDu and SCC15 cells in vitro; however, ANXA6 knockdown retarded LM in HNSCC in vivo. ANXA6 induced autophagy by inhibiting the AKT/mTOR signaling pathway in HNSCC, thereby regulating the metastatic capability of the disease. Furthermore, ANXA6 expression positively correlated with TRPV2 expression both in vitro and in vivo. Lastly, TRPV2 inhibition reversed ANXA6-induced autophagy and LM. These results indicate that the ANXA6/TRPV2 axis facilitates LM in HNSCC by stimulating autophagy. This study provides a theoretical basis for investigating the ANXA6/TRPV2 axis as a potential target for the treatment of HNSCC, as well as a biomarker for predicting LM.


Leiomyosarcoma of the inferior vena cava presenting as a suprarenal mass.
Leiomyosarcoma of the inferior vena cava is a rare disease with protean manifestations related to the location of the tumor. Urological manifestations of the disease are rare and include renal vein thrombosis and renovascular hypertension. Approximately 63 cases have been reported in the literature, with a striking female predominance. Presentation as an isolated suprarenal mass has not been reported previously. We discuss this unusual tumor and report a case that presented as an asymptomatic suprarenal mass.


How does diabetes type 1 affects immune response to hepatitis B virus vaccine in pediatric population? Evaluation of a booster dose in unresponsive subjects with type 1 diabetes.
Hepatitis B virus (HBV) vaccine reduced the incidence of Hepatitis B worldwide. Genetic variability, by the presence of specific haplotypes of HLA system (HLA-DR3, HLA-DR4), influences the response to the vaccination. Subjects affected by type 1 diabetes (T1D), contrary to non-diabetics, have a high prevalence of Hepatitis B. The objective of the study was to evaluate anti-HBs antigen (anti-HBsAg) antibody (Ab) in a group of 201 children (age range: 2-18 years), regularly vaccinated against HBV according to the national vaccination schedule. Patients with anti-HBs Ab≥10 mIU/mL have been defined "responders" and those with anti-HBs Ab<10mIU/mL have been defined "non-responders." The possible association between the T1D and a low immune response to the vaccine has been subsequently valued. Besides the presence of T1D, other possible influential variables have been studied: sex, age, presence of celiac disease and Hashimoto's thyroiditis, intervening years from the diagnosis of diabetes and presence/absence of diabetic ketoacidosis at time of diagnosis. Among the 201 subjects with T1D, 90 (44.8%) were responders, while 111 (55.2%) were non-responders; among the 145 subjects without T1D, 86 (59.3%) were responders and 59 (40.7%) non-responders. We invited "Subjects with T1D non-responders" to undergo a booster dose of the same vaccine. Of these, 21 refused the booster, reducing the sample to 90 patients. After 4 weeks from the booster dose 81 patients showed seroconversion ("false non-responders"), and 9 did not ("true non-responders"). After the booster dose, immune response in our cross-section has been similar to general population. Given the high frequency of "false non-responders" anti-HBsAg Ab should be tested in T1D patients and a booster dose should be administrated in non-responders.


Unlocking community capabilities for addressing social norms/practices: behavioural change intervention study to improve birth preparedness and complication readiness among pregnant women in rural Nigeria.
Maternal mortality is attributed to combination of contextual factors that cause delay in seeking care, leading to poor utilization of skilled health services. Community participation is one of the acknowledged strategies to improve health services utilization amongst the poor and rural communities. The study aimed at assessing the potentials of improving birth preparedness and complication readiness (BP/CR) using community-driven behavioural change intervention among pregnant women in rural Nigeria. A pre-post intervention study was conducted from June 2018 to October 2019 on 158 pregnant women selected through multi-stage sampling technique from 10 villages. Data on knowledge and practices of birth preparedness and utilization of facility health services were collected through interviewer-administered pre-tested structured questionnaire. Behavioural change intervention comprising of stakeholders' engagement, health education, facilitation of emergency transport and fund saving system, and distribution of educational leaflets/posters were delivered by twenty trained volunteer community health workers. The intervention activities focused on sensitization on danger signs of pregnancy, birth preparedness and complication readiness practices and emergency response. Means, standard deviations, and percentages were calculated for descriptive statistics; and T-test and Chi square statistical tests were carried out to determine associations between variables. Statistical significance was set at p-value < 0.05. The result showed that after the intervention, mean knowledge score of danger signs of pregnancy increased by 0.37 from baseline value of 3.94 (p < 0.001), and BP/CR elements increased by 0.27 from baseline value of 4.00 (p < 0.001). Mean score for BP/CR practices increased significantly by 0.22 for saving money. The proportion that had antenatal care (76.6%) and had facility delivery (60.0%) increased significantly by 8.2 and 8.3% respectively. Participation in Community-related BP/CR activities increased by 11.6% (p = 0.012). With the improvements recorded in the community-participatory intervention, birth preparedness and complication readiness should be promoted through community, household and male-partner inclusive strategies. Further evaluation will be required to ascertain the sustainability and impact of the programme.


Effect of Piracetam on electrocorticogram and local cerebral glucose utilization in the rat.
The effect of Piracetam on hypoxia-induced alterations of cerebral cortex electrogenesis is studied. The results showed protection. As this anti-hypoxidotic property could be linked to Piracetam influence on energy-metabolic processes in the brain, we studied the effect of this nootropic drug on local cerebral glucose utilization (LCGU) by means of a variant of the Sokoloff's technique. Our results showed that Piracetam enhances LCGU. We suggest that both effects, the functional and the metabolic one, are related.


The healthcare burden and associated adverse events from total alloplastic temporomandibular joint replacement: a national United States perspective.
The purpose of this study was to provide a United States perspective on alloplastic total joint replacement. We sought to estimate the inpatient burden and report the most common adverse events using two administrative datasets. The National Inpatient Sample was queried from October 2015 to December 2016 for total joint replacement admissions using International Classification of Diseases 10th revision codes, and the Manufacturer and User Facility Device Experience registry was queried from January 2009 to September 2019 using manufacturer brands. The combined final sample included 114 inpatient admissions and 392 adverse events. Mean age was 43.1 years, and most patients were white (82.7%) and female (86.0%). The mean hospital charge was $108,709.43 and the mean length of stay was 2.6 days. The most common adverse events were infection (26.3%), heterotopic bone (20.9%), and poor intraoperative fit (14.0%). Fifty-four percent of cases had bilateral total joint replacements, 24.6% had simultaneous subcutaneous abdominal fat grafting, and 11.4% had simultaneous maxillary repositioning. Fat grafting and maxillary repositioning were not associated with any significant difference in the length of stay or cost. Compared to unilateral cases, bilateral total joint replacements carried significantly greater charges (P<0.01), but no increased length of stay (P=0.70), suggesting that bilateral and unilateral cases may experience a similar postoperative course.


Breaches of the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.
A subset of congenital muscular dystrophies (CMDs) has central nervous system manifestations. There are good mouse models for these CMDs that include POMGnT1 knockout, POMT2 knockout and Large(myd) mice with all exhibiting defects in dentate gyrus. It is not known how the abnormal dentate gyrus is formed during the development. In this study, we conducted a detailed morphological examination of the dentate gyrus in adult and newborn POMGnT1 knockout, POMT2 knockout, and Large(myd) mice by immunofluorescence staining and electron microscopic analyses. We observed that the pial basement membrane overlying the dentate gyrus was disrupted and there was ectopia of granule cell precursors through the breached pial basement membrane. Besides these, the knockout dentate gyrus exhibited reactive gliosis in these mouse models. Thus, breaches in the pial basement membrane are associated with defective dentate gyrus development in mouse models of congenital muscular dystrophies.


Factors affecting access to health services by older adults in an urban community in Thailand: a cross-sectional study.
Background: The impending rapid change in Thailand's older population has many important implications for health policy, especially older adults' health problems, which are major cause of them accessing health services. This study aimed to study factors affecting access to health services for older adults in urban communities in Thailand, as well as performing a situational survey of health service utilization. Methods: This cross-sectional study included 886 older adults from four types of urban communities (slum, city, suburban, and community building). Data were collected using an interview questionnaire. Information about health service variables were extracted and followed the five dimensions of accessibility by Penchansky & Thomas: availability, accessibility, accommodation, affordability and acceptability. Data were analyzed using percentage mean and standard deviation (SD). Analysis of factors affecting access to health service was performed using Logistic regression. Results: The utilization of health services was high among five dimensions. They were composed of availability (mean 4.2, SD.=0.59), accessibility (mean 4.1, SD.=0.69), accommodation (mean 3.9, SD.=0.67), affordability (mean 4.2, SD.= 0.62), and acceptability (mean 4.1, SD.=0.62). A summary of all dimensions revealed a mean of 4.1 (SD.= 0.52). Factors affecting older adults access to health services were using health insurance rights for health care service, and concern about the necessity of health care. Conclusions: Encouraging older adults to change their health insurance rights to the nearest hospital and promoting the provision of holistic health information, which will support older adults in accessing more health services to improve their health outcomes.


A positive blood alcohol concentration is the main predictor of recurrent motor vehicle crash.
The identification of risk factors for recurrent motor vehicle crashes is the basis for prevention, but few studies have been published on predictors of recurrence. Our objective is to determine the main variables predicting recurrent crashes in subjects attending an emergency department (ED) for injuries after motor vehicle crash. During a 5-year follow-up period, we studied 2,354 consecutive adult subjects treated in the ED after a motor vehicle crash in 1998. The variables of the original event were tested for predicting recurrence in a Cox proportional hazard model. During follow-up, 390 of 2,325 (16.8%) survivors were treated for injury after a new crash. The overall event rate was 34 per 1,000 subject-years. Four variables (age < or =32 years, male sex, nighttime crash, and blood alcohol concentration >50 mg/dL) were identified as independent predictors of recurrent crash. After adjustment for sex, age, and nighttime, alcohol was the leading predictor (relative risk 3.73; 95% confidence interval 3.00 to 4.64). In the presence of the 4 variables, the recurrence rate was as high as 145 (117 to 175) events per 1,000 subject-years, and alcohol per se accounted for more than 75% of events. In the absence of the 4 variables, the rate was as low as 11 (7 to 17) events per 1,000 subject-years. Alcohol was the most powerful behavioral factor predicting recurrent events in subjects treated in an ED for injury after motor vehicle crash, along with young age, male sex, and nighttime.


Evaluation of serum prostate-specific antigen in urologic cancers.
Serum prostate-specific antigen (PA), a new tumor marker of prostate cancer, was evaluated with an eznyme immunoassay (EIA) in various urologic cancer patients and benign prostatic diseases in Japanese. Sera of prostate cancer patients before treatment (n = 27) revealed a range of PA concentrations from 0.12-23 ng/ml with a mean (+/- SD) of 5.78 +/- 6.85 ng/ml, while that of patients with benign prostatic hypertrophy (BPH) (n = 27) showed from less than 0.10 to 2.6 ng/ml with 0.84 +/- 0.81 ng/ml (mean +/- SD). The mean serum PA levels in nonprostatic cancers were calculated as follows: bladder cancer (n - 21), 0.77 +/- 0.55 ng/ml; renal pelvis or ureteral cancer (n = 6), 0.46 +/- 0.47 ng/ml; renal adenocarcinoma (n equal to 6), 1.07 +/- 0.77 ng/ml; other urologic cancers (n = 6), 0.55 +/- 0.52 ng/ml. Serum PA ranged from less than 0.10 to 1.1 ng/ml in patients with prostatitis (n = 5). A significant statistical difference in serum PA levels between prostate cancer and other groups was recognized. These results suggested that an elevation of serum PA value was highly specific to prostate cancer in urological malignancies. The evaluation of serum PA may be of great value in the detection of prostate cancer.