Diagnosis and surgical correction of cor triatriatum in an adult: combined use of transesophageal and contrast echocardiography, and a review of literature.
Cor triatriatum is rarely found in adults and its diagnosis is mostly dependent on transesophageal echocardiogram. We present a case of an adult male with cor triatriatum and discuss our approach to diagnosis with a review of literature. A 49-year-old male presented with progressive exertional dyspnea for the past two-and-half years. A transthoracic echocardiogram revealed a thin linear echo-dense structure traversing the left atrium (LA). A transesophageal echocardiogram demonstrated a thin immobile membrane in the LA attached medially to the interatrial septum. No fenestration of the membrane was seen. A swirling spontaneous contrast was noted in the posterior chamber. Color Doppler did not reveal any flow across the membrane. A CT scan of the chest was unhelpful to differentiate extracardiac versus intracardiac origin. Contrast echocardiogram with Optison was performed, which showed a differential opacification of the two atrial chambers and delayed emptying of contrast into true LA establishing communication between the chambers. Left and right heart catheterization were performed with simultaneous pulmonary capillary wedge and left ventricular end diastolic pressure measurement, revealing a mean gradient of 17 mmHg. Surgical correction of the membrane was recommended. Intraoperatively, an orifice of 0.7 cm was identified in an eccentric position with mosaic pattern of continuous turbulent flow across the membrane by color Doppler. Our case demonstrates the impact of contrast echocardiography in a situation where the transesophageal approaches were limited even with the aid of color Doppler.


The effect of ipratropium nasal spray on bronchial methacholine challenge.
To determine the effect ipratropium bromide nasal spray has on methacholine challenge testing for airway hyperresponsiveness. Ten subjects with known airway hyperresponsiveness to methacholine who had been clinically stable in the preceding 2 months participated in a randomized, double-blind, placebo-controlled, crossover study. Methacholine challenge testing was conducted on successive days: day 1 after pretreatment with aqueous 0.03% nasal ipratropium, and day 2 with normal saline solution placebo. The provocative concentration of methacholine causing a 20% fall in FEV1 (PC20) was higher after nasal ipratropium than after saline solution placebo (2.1 mg/mL vs 1.6 mg/mL, p = 0.02). This difference is equal to approximately one-half concentration difference, probably within the limits of reproducibility of the test. Pretreatment with nasal ipratropium results in a small increase in PC20. Although this difference achieves statistical significance, it is probably not clinically significant.


Neurocognitive individualized training versus social skills individualized training: a randomized trial in patients with schizophrenia.
Rehabilitation programs integrating cognitive remediation (CR) and psychosocial rehabilitation are often implemented as they seem to yield greater improvements in functional outcome than stand alone treatment approaches. Mechanisms underlying synergistic effects of combining CR with psychosocial interventions are not fully understood. Disentangling the relative contribution of each component of integrated programs might improve understanding of underlying mechanisms. In the present study we compared the efficacy of two components of our rehabilitation program [the Neurocognitive Individualized Training (NIT) and the Social Skills Individualized Training (SSIT)]. Seventy-two patients with schizophrenia or schizoaffective disorder were randomly assigned to one of two treatment groups. Changes in cognitive, psychopathological and real-world functioning indices after 6 and 12 months were compared between the two groups. After both 6 and 12 months, NIT produced an improvement of attention, verbal memory and perseverative aspects of executive functioning, while SSIT produced a worsening of visuo-spatial memory and attention and no significant effect on the other cognitive domains. As to the real-world functioning, NIT produced a significant improvement of interpersonal relationships, while SSIT yielded a significant improvement of QLS instrumental role subscale. According to our findings, cognitive training is more effective than social skills training on several cognitive domains and indices of real-world functioning relevant to subject's relationships with other people. Integrated approaches might target different areas of functional impairment but should be planned carefully and individually to fully exploit the synergistic potential.


Multiple Sequence Alignment based on deep Q network with negative feedback policy.
Multiple Sequence Alignment (MSA) is an essential procedure in the sequence analysis of biological macromolecules, which can obtain the potential information between multiple sequences, such as functional and structural information. At present, the main challenge of MSA is an NP-complete problem; the algorithm's complexity increases exponentially with the increase of the number of sequences. Some methods are constantly approaching the results towards the optimal ratio and easy to fall into the local optimization, so the accuracy of these methods is still greatly improved. Here, we propose a new method based on deep reinforcement learning (DRL) for MSA. Specifically, inspired by biofeedback, we leverage the Negative Feedback Policy (NFP) to enhance the performance and accelerate the convergence of the model. Furthermore, we developed a new profile algorithm to compute the sequence from aligned sequences for the next profile-sequence alignment to facilitate the experiment. Compared to six state-of-the-art methods, three different genetic algorithms, Q-learning, ClustalW, and MAFFT, our method exceeds these methods in terms of Sum-of-Pairs (SP) score and Column Score(CS) scores on most datasets in which the increased range of SP score is from 2 to 1056. Extensive experiments based on several datasets validate the effectiveness of our method for achieving a better alignment, and the results have higher accuracy and stability. The source code can be found at https://github.com/MrZhang176/DNPMSA.


The role of transesophageal echocardiography in the diagnosis and treatment of right atrial thrombi.
Twenty patients with right atrial thrombi were identified through the use of transthoracic and transesophageal echocardiography. Transesophageal echocardiography identified right atrial thrombi in all 20 cases. Transthoracic echocardiography showed definite thrombi in only 6 (30%) cases and suggested thrombus in another 2 (10%) patients. Thus transthoracic echocardiography results were false-negative for right atrial thrombus in 60% of cases. All 3 thrombi found within the right atrial appendage and 2 of 3 thrombi on pacemaker wires were missed by transthoracic echocardiography. There was no significant difference in the mean size between those thrombi seen (1.37 +/- 0.6 cm) and those missed (1.5 +/- 0.9 cm) by transthoracic echocardiography. Transesophageal echocardiography also significantly affected treatment. Anticoagulation was initiated or amplified in 13 patients. In 8 of these 13, thrombi were seen only by transesophageal echocardiography. Surgery was performed to remove thrombi in 7 cases, and in 3 (43%) cases it was because of thrombi seen only by transesophageal echocardiography. This study suggests that transesophageal echocardiography should be performed whenever right atrial thrombi are suspected. Transesophageal echocardiography has a significant effect on the diagnosis and management of patients with right atrial thrombi.


Aldosterone and the mobilization of energy.
Aldosterone diminishes the ability to endure starvation. Its exogenous administration to adrenalectomized rats advances the onset of hypothermia and death. The impairment seems to lie in an inability to mobilize energy stores fully: animals given the steroid are unable to lose weight at a normal rate. The findings help to establish the significance of mineralocorticoids in the regulation of energy exchange and solve some theoretical questions as to their general mode of action.


Pentoxifylline and vitamin E reduce the severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients: a randomized, controlled study.
The purpose of this study was to assess the impact of pentoxifylline and vitamin E on the incidence and severity of radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients. This is a prospective, randomized, controlled study. Head and neck cancer patients receiving 30-35 radiotherapy fractions with or without concurrent chemotherapy excluding those intolerant to xanthines, with any bleeding tendency were included. Sixty patients were enrolled; 30 patients received radiotherapy (control group) and 30 patients received radiotherapy with pentoxifylline and vitamin E (intervention group). The incidence, severity, onset and duration of oral mucositis and/or dysphagia were assessed. Locoregional control, quality of life, need for hospitalization, radiotherapy breaks, and adverse events were recorded and compared between groups. Pentoxifylline and vitamin E combination did not affect the incidence or the onset of oral mucositis or dysphagia. After adjusting for age, the combination reduced the incidence of severe oral mucositis (p = 0.01) and dysphagia (p = 0.012). The combination decreased the duration of oral mucositis and dysphagia by 5 weeks (p = 0.002) and 4 weeks (p = 0.003), respectively. The study drugs reduced the need for hospitalization (p = 0.002) and for radiotherapy breaks (p = 0.002) with improvement of FOIS (p = 0.014), EQ-5D index (p = 0.009) and VAS score (p = 0.012). Pentoxifylline and vitamin E decreased the occurrence of dysgeusia (p = 0.026) and fatigue (p = 0.026) without compromising locoregional control. Pentoxifylline/vitamin E combination reduced the severity and duration of acute radiotherapy-induced oral mucositis and dysphagia in head and neck cancer patients.Trial registry ClinicalTrials.gov registration number: NCT02397486.


Magnetic bead protamine-linked microtiter assay for detection of heparin using iodinated low-molecular-mass heparin-tyramine.
We have developed a competitive heparin binding assay employing protamine-coated magnetic beads for detection and measurement of heparin. The assay utilizes 125-iodine specifically bound to newly synthesized low-molecular-mass (LMM) heparin-tyramine. The tracer was stable over a period of 3 weeks, as demonstrated by gel filtration chromatography. The protamine-coated beads were found to be stable over at least two months. The heparin-tyramine bead assay had in buffer a lower detection limit of 0.04 microgram/ml and in plasma of 0.23 microgram heparin/ml. 50% binding was obtained at 0.7 microgram/ml and 20% binding at 4 micrograms/ml in plasma. The within assay coefficient of variation ranged from 9 to 28% for unfractionated, high molecular mass (HMM) heparin and from 12 to 15% for LMM-heparins in buffer system and in plasma. Various heparin fractions displaced the tracer from the protamine-coated magnetic beads to different extents. The validity of the assay was proven after intravenous administration of unfractionated and LMM-heparin in man. The elimination rate was similar using the heparin-tyramine bead assay compared with the anti-factor Xa coagulation assay. After intravenous dosing of LMM-heparin the maximal concentration was lower using the heparin-tyramine bead assay compared with the anti-factor Xa coagulation assay. The bead assay was found to be reproducible, valid, and rapid for measurement of the concentration of heparin preparations in purified systems and for HMM-heparin in plasma. Measurement of the concentration of LMM-heparin in plasma has a high coefficient of variation using the binding assay.


Large-scale purification of plasmid insert DNA sequences using low-percentage agarose exclusion chromatography.
Linear double-stranded DNA fragments ranging from 0.14 to 8.4 kbp have been fractionated on low-percentage agarose exclusion gels. Both Ultragel A2 (2% agarose) and Bio-Gel A150m (1% agarose) exclude DNA fragments greater than 900 bp, while the exclusion limit of Bio-Gel A50m (2% agarose) is about 350 bp. All gels result in moderate resolution of DNA fragments smaller than the exclusion limits; we generally observe nearly complete one-step separation of fragments that differ in size by a factor of 2. On the basis of these results, we have used these exclusion gels to routinely purify greater than 0.4 mg of plasmid insert DNA sequences in one step and over 2.5 mg with a single column, demonstrating that these gel matrices can be ideally suited for repeated rapid large-scale purification of plasmid inserts. In addition, this knowledge allows for a more rational design of plasmids in those cases where large-scale use of the insert DNA is required.


Pecs Blocks for Chronic Pain: A Case Report of Successful Postmastectomy Pain Syndrome Management.
Mastectomies can be complicated by difficult-to-treat postmastectomy pain syndrome (PMPS) and axillary web syndrome (AWS). We present a case of PMPS and AWS successfully treated with Pecs I and II blocks and trigger point injections. At follow-up after 4 months, our patient reported 70% improvement in pain, movement, function, and discontinuation of opioids. This case presents the utility of a multimodal approach for a patient with pain after mastectomy. This case report is the first-time demonstration of Pecs blocks to treat chronic PMPS.


Sustainable production of biofuels from the algae-derived biomass.
The worldwide fossil fuel reserves are rapidly and continually being depleted as a result of the rapid increase in global population and rising energy sector needs. Fossil fuels should not be used carelessly since they produce greenhouse gases, air pollution, and global warming, which leads to ecological imbalance and health risks. The study aims to discuss the alternative renewable energy source that is necessary to meet the needs of the global energy industry in the future. Both microalgae and macroalgae have great potential for several industrial applications. Algae-based biofuels can surmount the inadequacies presented by conventional fuels, thereby reducing the 'food versus fuel' debate. Cultivation of algae can be performed in all three systems; closed, open, and hybrid frameworks from which algal biomass is harvested, treated and converted into the desired biofuels. Among these, closed photobioreactors are considered the most efficient system for the cultivation of algae. Different types of closed systems can be employed for the cultivation of algae such as stirred tank photobioreactor, flat panel photobioreactor, vertical column photobioreactor, bubble column photobioreactor, and horizontal tubular photobioreactor. The type of cultivation system along with various factors, such as light, temperature, nutrients, carbon dioxide, and pH affect the yield of algal biomass and hence the biofuel production. Algae-based biofuels present numerous benefits in terms of economic growth. Developing a biofuel industry based on algal cultivation can provide us with a lot of socio-economic advantages contributing to a publicly maintainable result. This article outlines the third-generation biofuels, how they are cultivated in different systems, different influencing factors, and the technologies for the conversion of biomass. The benefits provided by these new generation biofuels are also discussed. The development of algae-based biofuel would not only change environmental pollution control but also benefit producers' economic and social advancement.


Headache in a Child with Pseudohypoparathyroidism: An Alarming Symptom Not to Miss.
While the endocrine manifestations of pseudohypoparathyroidism are well known, less is known about the associated brain and spine abnormalities. These abnormalities may present with nonspecific symptoms in the paediatric population, and lack of awareness to these uncommon manifestations of the disease may result in a delay in necessary intervention. Case Presentation. We herein present a case of known pseudohypoparathyroidism type 1a who presented initially with minor head injury. She later developed progressive worsening headache, increased irritability, and vomiting. Repeated imaging showed hydrocephalus and Chiari malformation type 1 necessitating emergency craniectomy. Growth hormone deficiency, a common manifestation of pseudohypoparathyroidism type 1a, results in underdevelopment of the posterior cranial fossa and may account for the higher incidence of Chiari malformation in this group of patients. Other associated neurological features reported in pseudohypoparathyroidism type 1a include spinal stenosis, syringomyelia, and craniosynostosis. While less commonly seen, awareness to these associations is important in order to optimize the multidisciplinary care to this group of patients.


Evaluating the impact of stay-at-home orders on the time to reach the peak burden of Covid-19 cases and deaths: does timing matter?
The economic, psychological, and social impact of pandemics and social distancing measures prompt the urgent need to determine the efficacy of non-pharmaceutical interventions (NPIs), especially those considered most stringent such as stay-at-home and self-isolation mandates. This study focuses specifically on the impact of stay-at-home orders, both nationally and internationally, on the control of COVID-19. We conducted an observational analysis from April to May 2020 and included both countries and US states with known stay-at-home orders. Our primary exposure was the time between the date of the first reported case of COVID-19 to an implemented stay-at-home mandate for each region. Our primary outcomes were the time from the first reported case to the highest number of daily cases and daily deaths. We conducted linear regression analyses, controlling for the case rate of the outbreak in each respective region. For countries and US states, a longer period of time between the first reported case and stay-at-home mandates was associated with a longer time to reach both the peak daily case and death counts. The largest effect was among regions classified as the latest 10% to implement a mandate, which in the US, predicted an extra 35.3 days (95% CI: 18.2, 52.5) to the peak number of cases, and 38.3 days (95% CI: 23.6, 53.0) to the peak number of deaths. Our study supports the association between the timing of stay-at-home orders and the time to peak case and death counts for both countries and US states. Regions in which mandates were implemented late experienced a prolonged duration to reaching both peak daily case and death counts.


Executive Function: Association with Multiple Reading Skills.
Executive function (EF) is related to reading. However, there is a lack of clarity around (a) the relative contribution of different components of EF to different reading components (word reading, fluency, comprehension), and (b) how EF operates in the context of known strong language predictors (e.g., components of the Simple View of Reading or SVR), and other skills theoretically related to reading (e.g., vocabulary, processing speed) and/or to EF (e.g., short-term memory, motor function). In a large sample of 3rd to 5th graders oversampled for struggling readers, this paper evaluates the impact of EF derived from a bifactor model (Cirino, Ahmed, Miciak, Taylor, Gerst, & Barnes, 2018) in the context of well-known covariates and demographics. Beyond common EF, five specific factors (two related to working memory, and factors of fluency, self-regulated learning, and behavioral inattention/metacognition) were addressed. EF consistently showed a unique contribution to already-strong predictive models for all reading outcomes; for reading comprehension, EF interacted with SVR indices (word reading and listening comprehension). The findings extend and refine our understanding of the contribution of EF to reading skill.


Possible high dosage gentamycin therapy in infected neutropenic patients.
Serum gentamycin levels have been studied in 23 neutropenic infected patients after high doses (62 mg/m2 and 72 mg/m2) of the drug, we observed: a higher gentamicin level than with an usual dosage, levels under the ototoxic 10/ml level, no renal failure, and, no patient ototoxicity.


Intracoronary Thrombolysis in ST-Segment Elevation Myocardial Infarction Patients Undergoing Primary Percutaneous Coronary Intervention: an Updated Meta-analysis of Randomized Controlled Trials.
Primary percutaneous coronary intervention (PPCI) is the standard reperfusion treatment in ST-segment elevation myocardial infarction (STEMI). Intracoronary thrombolysis (ICT) may reduce thrombotic burden in the infarct-related artery, which is often responsible for microvascular obstruction and no-reflow. We conducted, according to the PRISMA statement, the largest meta-analysis to date of ICT as adjuvant therapy to PPCI. All relevant studies were identified by searching the PubMed, Scopus, Cochrane Library, and Web of Science. Thirteen randomized controlled trials (RCTs) involving a total of 1876 patients were included. Compared to the control group, STEMI ICT-treated patients had fewer major adverse cardiac events (MACE) (OR 0.65, 95% CI, 0.48-0.86, P = 0.003) and an improved 6-month left ventricular ejection fraction (MD 3.78, 95% CI, 1.53-6.02, P = 0.0010). Indices of enhanced myocardial microcirculation were better with ICT (Post-PCI corrected thrombolysis in myocardial infarction (TIMI) frame count (MD - 3.57; 95% CI, - 5.00 to - 2.14, P < 0.00001); myocardial blush grade (MBG) 2/3 (OR 1.76; 95% CI, 1.16-2.69, P = 0.008), and complete ST-segment resolution (OR 1.97; 95% CI, 1.33-2.91, P = 0.0007)). The odds for major bleeding were comparable between the 2 groups (OR 1.27; 95% CI, 0.61-2.63, P = 0.53). The present meta-analysis suggests that ICT was associated with improved MACE and myocardial microcirculation in STEMI patients undergoing PPCI, without significant increase in major bleeding. However, these findings necessitate confirmation in a contemporary large RCT.


HLA-B27-associated arthropathy in childhood: long-term clinical and diagnostic outcome.
We conducted HLA-B27 tissue typing assessments on 430 consecutive children whose main symptom at presentation to our clinic was arthritis/arthralgia. Eighty-five of them (20%) had the B27 antigen. Thirty-six of these children were reexamined after a mean followup period of 8.9 years. Although most had definable rheumatic diseases, only 2 met the New York criteria for ankylosing spondylitis (AS). Children with HLA-B27 and arthritis/arthralgia, although at increased risk of developing AS, have diverse diagnostic and clinical outcomes. The AS criteria used to diagnose the disease in adults may not be appropriate for use in children.


Enhanced anti-cancer effect of artemisinin- and curcumin-loaded niosomal nanoparticles against human colon cancer cells.
Colorectal cancer (CRC) is the third broadly identified cancer in the world. The ineffectiveness of colorectal cancer treatment is redundantly reported. Natural bioactive compounds have gained popularity in reducing the drawback of conventional anti-cancer agents. Curcumin (Cur) and Artemisinin (Art) are materials of a natural source that have been utilized to treat numerous kinds of cancers. Although the benefits of bioactive materials, their utilization is limited because of poor solubility, bioavailability, and low dispersion rate in aqueous media. Nano delivery system such as niosome can improve the bioavailability and stability of bioactive compounds within the drug. In current work, we used Cur-Art co-loaded niosomal nanoparticles (Cur-Art NioNPs) as an anti-tumor factor versus colorectal cancer cell line. The synthesized formulations were characterized using dynamic light scattering, scanning electron microscopy, and FTIR. The proliferation ability of the cells and expression of apoptosis-associated gene were MTT assay and qRT-PCR, respectively. Cur-Art NioNPs exhibited well distributed with an encapsulation efficiency of 80.27% and 85.5% for Cur and Art. The NioNPs had good release and degradation properties, and had no negative effect on the survival and proliferation ability of SW480 cells. Importantly, nanoformulation form of Cur and Art significantly displayed higher toxicity effect against SW480 cells. Furthermore, Cur-Art NioNPs increased Bax, Fas, and p53 gene expressions and suppressed Bcl2, Rb, and Cyclin D 1 gene expressions. In summary, these results display the niosome NPs as a first report of nano-combinational application of the natural herbal substances with a one-step fabricated co-delivery system for effective colorectal cancer.


The diagnosis of the small resectable pancreatic carcinoma.
ERCP and angiography are essential for the accurate diagnosis of pancreatic carcinoma. ERCP is of value in detecting a pancreatic tumour and is the only examination which makes it possible to detect a small pancreatic carcinoma. Angiography is indispensable for the evaluation of the extent and size of the carcinoma, for prediction of resectability, and for differentiation between pancreatitis and carcinoma. Thirty-one out of 32 pancreatic carcinomas (96%) were correctly diagnosed pre-operatively by the use of a combination of the two examinations. Ten of them (31%) were resectable, and of these six measured less than 2 cm in diameter.


Urotensin II-immunoreactive neurons in the caudal neurosecretory system of freshwater and seawater fish.
Antiserum generated against synthetic urotensin II of the goby, Gillichthys mirabilis, was used to localize urotensin II in the caudal neurosecretory system in six species of freshwater teleosts: Cyprinus carpio, Carassius auratus, Oreochromis mossambicus, Oreochromis niloticus, Salmo gairdneri and Plecoglossus altivelis, and six species of seawater teleosts: Acanthogobius flavimanus, Pagrus major, Parapristipoma trilineatum, Trachurus japonicus, Seriola dumerili and Seriola quinqueradiata. In the carp, urotensin II-immunoreactive perikarya were classified into three groups according to their size and shape. Small cells were located in the spinal cord dorsal to the urophysis, medium-sized cells immediately anterior to the urophysis, and large cells anterior to the medium-sized cells. In each group, a small number of nonreactive cells was found. Urotensin II-immunoreactive nerve fibers extended toward the urophysis and terminated around the blood vessels. Other species of teleosts showed a similar immunoreaction to that observed in the carp. The immunoreaction of the urophysis was stronger in seawater fish than freshwater fish. Urotensin II-immunoreactive elements could not be detected in the brains of the carp, goldfish and goby.


Characteristics of NADH-dependent lipid peroxidation in sarcoplasmic reticulum of white shrimp, Litopenaeus vannamei, and freshwater prawn, Macrobrachium rosenbergii.
The iron-catalyzed NADH-dependent lipid peroxidation system in sarcoplasmic reticulum (SR) of cultured white shrimp, Litopenaeus vannamei and freshwater prawn, Macrobrachium rosenbergii was characterized. Production of thiobarbituric acid reactive substances was used to measure the activity of lipid peroxidation. In both species, the system preferred NADH to NADPH as the reducing agent. Lipid peroxidation activities of SR from both species increased when reaction temperatures increased from 6 to 26 degrees C. At 66 degrees C, the reaction was no longer NADH-dependent. Acidic pH amplified the lipid peroxidation activity. Sarcoplasmic reticular lipid peroxidation activity in white shrimp was always greater than in freshwater prawn. Fatty acid composition of SR lipids could be a major factor for this outcome. The proportion of n-3 highly unsaturated fatty acids, such as C20:5 and C22:6, in sarcoplasmic reticular lipids of white shrimp was twice of that in freshwater prawn. The results of this study provide important tools required for anti-oxidative nutrient study at sub-cellular level.


Efficacy of a porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) natural recombinant against a heterologous PRRSV-1 isolate both clustered within the subgroup of BJEU06-1-like isolates.
Porcine reproductive and respiratory syndrome virus 1 (PRRSV-1) has been prevalent in more than 20 provinces of China. However, no PRRSV-1-specific vaccine is commercially available in China. To evaluate the feasibility of using a low virulent PRRSV-1 isolate against potential outbreaks caused by virulent Chinese PRRSV-1 isolates, here we evaluated the efficacy of a low virulent PRRSV-1 HLJB1 strain isolated in 2014 as live vaccine against a virulent PRRSV-1 SD1291 strain isolated in 2022. Genome-based phylogenetic analysis showed that both HLJB1 and SD1291 were grouped within BJEU06-1-like isolates. However, they shared only 85.27% genomic similarity. Piglet inoculation and challenge study showed that HLJB1 inoculation could reduce viremia but did not significantly alleviate clinical signs and tissue lesions. Virus neutralization test indicated that HLJB1 inoculation could induce homologous neutralizing antibodies (NAbs) but no heterologous NAbs at 42 dpi. In addition, flow cytometric analyses showed that no memory T follicular helper (Tfh) cells against SD1291 and SD1291-specific IFN-γ secreting cells were induced by HLJB1 pre-inoculation. These results supported that HLJB1 inoculation only provides partial cross-protection against SD1291 infection even though they are clustered within the same PRRSV-1 subgroup, which is closely related to the failure in conferring cross-protective adaptive immune responses.


Dichloroacetate derivatives. Metabolic effects and pharmacodynamics in normal rats.
Dichloroacetate (DCA) reduces blood glucose, lactate and lipids in diabetes or during fasting. Chronic use of DCA, however, is limited by toxicity, probably due in part to its rapid conversion to oxalate in vivo. In theory, therefore, DCA's efficacy may be retained and its toxicity minimized by controlling its rate of metabolism. We attempted to alter DCA pharmacokinetics and bioavailability by synthesizing various derivatives comprising DCA esters with polyols and DCA ionic complexes. Twenty-four hour fasted, nondiabetic rats received single, orogastric doses of saline (control) sodium DCA (100mg/kg) or the following derivatives (D1-4): the esters D1-D3: potassium tetra (dichloroacetyl) glucuronate (D1), inositol-monophosphate-tetradichloroacetate (D2), inositol-hexadichloroacetate (D3) and inositol-hexa [N-methylnicotinate] hexadichloroacetate salt (D4). Each derivative was administered at a dose that would ultimately provide 100 mg/kg DCA as the anion. All derivatives were orally effective in significantly decreasing blood glucose and lactate. D4 exerted the most potent and long-lasting glucose- and lactate-lowering effects, yet increased plasma DCA concentrations less than an equivalent dose of the sodium salt. When administered to reverse light-cycled rats, D4 markedly inhibited the incorporation of tritiated water into cholesterol and triglycerides. We conclude that derivatives of DCA retain the biological activity of the parent compound, but may exhibit different pharmacokinetics. They may eventually prove useful in the treatment of diabetes mellitus, hyperlipidemia and lactic acidosis in man.


Origin of the thalamic projection to dorsal auditory cortex in hearing and deafness.
While it is now well accepted that the brain reorganizes following sensory loss, the neural mechanisms that give rise to this plasticity are not well understood. Anatomical tract tracing studies have begun to shed light on the structural underpinnings of cross-modal reorganization by comparing cerebral connectivity in sensory-deprived animals to that of their non-deprived counterparts. However, so far, full documentation of connectional patterns within hearing, congenitally deaf, as well as animals deafened early versus later in life exist only for primary auditory cortex, a region not known to undergo cross-modal reorganization in the deaf. The purpose of the present investigation was to examine thalamo-cortical patterns of connectivity in hearing, late- and early-deafened cats to the dorsal zone (DZ), a region of auditory cortex that cross-modally reorganizes to mediate enhanced visual motion perception following deafness. In hearing cats, the largest projections to DZ arose from the dorsal division of the medial geniculate body (MGB) with lesser projections originating in the medial and ventral MGB and from the suprageniculate and the lateral posterior nuclei. In general, while some variations in the strength of specific thalamic projections were noted, the pattern of projections arising from the thalamus in early- and late-deafened animals remained consistent with that of hearing subjects. These results complement the existing thalamic connectivity data described for congenitally deaf animals, which together demonstrate that thalamo-cortical connectivity patterns to DZ are conserved following deafness, irrespective of the time of onset and etiology of deafness.


Rare frontal lobe intraparenchymal epidermoid cyst with atypical imaging.
Epidermoid cysts are slow-growing benign tumors derived from ectodermal tissue that are hypothesized to have been inwardly displaced from the ectodermal surfaces during embryologic development. These cysts represent 1% to 2% of all intracranial tumors, and occur most commonly in the cerebellopontine angle, parasellar region, and subarachnoid spaces of the basal cisterns. Epidermoid cysts that are exclusively intraparenchymal are very rare, and can be difficult to diagnose as they often do not have classic radiologic findings, and share many similar radiologic features to other tumors such as astrocytomas, arachnoid cysts, dermoid cysts, and cavernomas. The authors present a patient with a rare intraparenchymal epidermoid cyst of the frontal lobe with atypical imaging features.


The effect of low-dose ketamine on fentanyl-induced respiratory depression.
This study evaluated if adding low-dose ketamine to fentanyl could offer a haemodynamically stable drug combination with little respiratory side-effects. Eight healthy, consenting male volunteers received in a random, cross-over and double-blind fashion both fentanyl 2 micrograms.kg-1 + ketamine 0.25 mg.kg-1 and fentanyl 2 micrograms.kg-1 + placebo. The fentanyl and placebo reduced minute ventilation, alveolar ventilation and oxygen consumption (p < 0.05), with little effect on haemodynamics. After fentanyl and ketamine, the decrease in minute ventilation and alveolar ventilation was attenuated compared to the placebo-containing combination (p < 0.05), but with a simultaneous increase in oxygen consumption (p < 0.05) and stimulation of haemodynamics (p < 0.05). Both treatments decreased oxygen saturation and arterial oxygen pressure similarly. Ketamine thus attenuated the fentanyl-induced reduction in ventilation without preventing the decrease in blood oxygenation. In conclusion, combining low-dose ketamine to fentanyl offers no benefits in terms of preventing respiratory depression.


Fighting AIDS at home. Hospitals, physicians seek community AIDS strategies.
Experts say collaboration and coordination of AIDS services among providers and agencies can improve and streamline the delivery of care, as well as reduce unnecessary costs. Meanwhile, White House AIDS policy coordinator Kristine Gebbie has definite ideas about the next steps in handling the AIDS crisis.


A meta-analysis of the dose-response relationship of inhaled corticosteroids in adolescents and adults with mild to moderate persistent asthma.
Although inhaled corticosteroids (ICS) are commonly used in the treatment of persistent asthma, the relationship between dose and clinical response remains unclear. This study investigated whether ICS exhibit a dose-response relationship in the treatment of mild to moderate persistent asthma. This was a meta-analysis of published randomized clinical trials concerning the relationship between ICS dose and response in asthma. Relevant studies were identified through a search of PubMed and MEDLINE for articles on asthma and ICS published between January 1996 and January 2001. The search was limited to publications classified as clinical trials that included the text words asthma and corticosteroids, glucocorticoids, beclomethasone, budesonide, fluticasone, flunisolide, mometasone, or triamcinolone acetonide. Five clinical measures were considered: morning peak expiratory flow rate (AM PEFR), evening PEFR (PM PEFR), forced expiratory volume in 1 second (FEV(1)), beta-agonist use, and asthma symptom score (severity of symptoms on a given day, as evaluated by patients). Forty-three studies were identified, of which 16 met the criteria for inclusion in the meta-analysis. These studies involved 4 agents: fluticasone propionate, triamcinolone acetonide, budesonide, and mometasone furoate. A statistically significant dose response in AM PEFR was observed with fluticasone propionate, triamcinolone acetonide, and budesonide (respective 95% CIs, 4.9 to 11.5, 4.7 to 18.0, and 5.8 to 24.9). A statistically significant dose response to fluticasone propionate and triamcinolone acetonide was also observed in PM PEFR (95% CIs, 2.0 to 8.7 and 2.4 to 13.7) and asthma symptom score (95% CI, -0.069 to -0.002 and -0.60 to -0.10). In terms of FEV(1), the dose response was statistically significant only with budesonide (95% CI, 0.025 to 0.17). Dose-response relationships were not disproportionately driven by the highest doses, and the greatest effects on response were seen at doses below or at the low end of the recommended range, suggesting that use of high doses of ICS may contribute only marginally to efficacy. Dose-response relationships were not uniformly observed with all drugs or for all measures of response. Use of higher doses of ICS in patients with mild to moderate persistent asthma does not appear to increase the efficacy of these drugs.


Concept of Quantum Geometry in Optoelectronic Processes in Solids: Application to Solar Cells.
The concept of topology is becoming more and more relevant to the properties and functions of electronic materials including various transport phenomena and optical responses. A pedagogical introduction is given here to the basic ideas and their applications to optoelectronic processes in solids.


Adrenomyeloneuropathy: a rare cause of Addison's disease?
A 31-year-old male patient is reported who presented with neurological symptoms. He developed a urinary tract infection and an Addisonian crisis. This was due to adrenomyeloneuropathy, a form of X-linked adrenoleukodystrophy and characterized by accumulation of very-long-chain fatty acids in the adrenal cortex and nervous tissues.


Role stress amongst nurses at the workplace: concept analysis.
The present study explicates the concept of role stress amongst nurses through an analysis adopted from Walker and Avant; Strategies for Theory Construction in Nursing, 4th edn, Prentice Hall, New Jersey, NY. Role stress has become a significant problem amongst nurses and has created much distress leading to burnout among many in the nursing profession. It is significant to analyse the concept of role stress and its relative attributes and consequences, in order to recognize the necessary antecedents needed to create better conditions for nurses at the workplace. A modified method developed by Walker and Avant was used for this concept analysis. A model representing the concept of role stress was developed through careful consideration of the attributes, consequences, antecedents and empirical referents of role stress. The concept analysis of role stress among nurses at the workplace recognized the vulnerability of the nursing discipline towards burnout and distress in general. It is critical to be aware of the current state of health care and note the increased workload created for nurses. Nurses are at a greater vulnerability for role stress, making it imperative for health care organizations to critically evaluate and establish preventative measures for the concept of role stress.


CYP17A1 (rs74357) polymorphism and polycystic ovary syndrome risk: a systemic review and meta-analysis.
To investigate the association between CYP17A1 (rs74357) polymorphism and the risk of Polycystic Ovary Syndrome (PCOS). Literature on the association of CYP17rs74357 gene polymorphism and susceptibility to PCOS was retrieved by searching databases such as PubMed, Science Direct, Google Scholar and Embase from. The association measure was analyzed using an Odds Ratio (OR) and 95% Confidence Interval (CI). All the statistical analyses were executed using CMA 3.0 Software. In the present meta-analysis,24 studies including 3462 PCOS and 2898 controls were analyzed. The overall results validated that the 17 CYP17 T/C (rs74357) gene polymorphism was significantly associated with PCOS risk in 5 genetic models: recessive model (fixed and random effect), dominant model (random effect), CC vs. TT (fixed effect), CT vs. TT (fixed effect), and allele contrast (random effect). Stratified analyses by ethnicity/country also detected significant association between Asian and Caucasian under the recessive, dominant, CC vs. TT, CC vs. CT, and the allele contrast models. In the present study, CYP17 T/C (rs74357) gene polymorphism increase the susceptibility of PCOS, and the recessive C allele, can be proposed as a predictive factor for the risk of PCOS or an important pathway in PCOS associated metabolic and hormonal dysregulation especially insulin resistance.However, larger sample size andmultiracial studies are needed in the future to confirm the findings.


Retrospective Comparison of the Myopia Master and the Lenstar LS900 Axial Length Measurements in Children with Myopia.
This study is a retrospective analysis to compare ocular biometry measurements of axial length in children with myopia using Myopia Master (OCULUS, Wetzlar, Germany) and Lenstar LS900 (HAAG-STREIT AG, Köniz, Switzerland). Axial length measurements obtained with both instruments within a 3-week period were collected retrospectively. Measurements were visualized with a Bland-Altman plot. For statistical evaluation, a paired t-test was applied, and the Pearson correlation coefficient (r) was established. Sixty-one eyes from 31 myopic patients (59% male, 41% female) with a mean age of 11.34 ± 3.25 years (range: 6 - 18 years) were identified. Mean axial length was 24.7 mm (SD 1.29) with the Myopia Master and 24.69 mm (SD 1.30) with the Lenstar LS900 (Pearson correlation: r = 0.9991). The average difference of the axial length measurement between the two biometers was 0.00 064 mm ± 0.056 SD (p = 0.9293). The axial length measured by Myopia Master and Lenstar LS900 did not differ significantly. Thus, previous values obtained with the Lenstar LS900 can be applied to assess myopia progression.


Update on Clinical Outcomes of Highly Effective Modulator Therapy.
Based on the cystic fibrosis transmembrane conductance regulator (CFTR) genotype, approximately 90% of people with cystic fibrosis (CF) are candidates for highly effective modulator therapy (HEMT). Clinical trials conducted over the last 11 years have shown that these oral therapies substantially restore CFTR function, leading to improvements in lung function, nutritional status, and health-related quality of life. Here, we review safety and efficacy data from phase 3 clinical trials and observational studies which support the use of HEMT in most adults and children with CF. We also discuss opportunities for additional investigation in groups underrepresented or excluded from phase 3 clinical trials, and challenges in the evaluation of the safety and efficacy of HEMT at increasingly earlier stages of CFTR-mediated pathophysiology.


Nuclear localization signals enhance germline transmission of a transgene in zebrafish.
We report that cytoplasmic injection into zebrafish eggs of 10(4) copies of plasmid DNA complexed to nuclear localization signal (NLS) peptides, as compared to 10(6) copies of naked DNA, increased nuclear uptake of transgene DNA early during embryo development and enhanced transgene integration frequency into the germline of founders. Monitoring the dynamics of nuclear uptake of DNA-NLS complexes by fluorescence in situ hybridization (FISH) of interphase nuclei indicates that NLS enhances both the proportion of nuclei importing DNA during early embryo development, and the amount of DNA imported by individual nuclei. The use of NLS increases the proportion of germline transgenic founders from 14 to 43% (P < 0.01) as assessed by polymerase chain reaction analysis of F1s. From germline transgenic DNA-NLS-injected founders, 47% transgenic F1s are obtained in wild-type crosses, as opposed to 6% from naked DNA-injected founders (P < 0.01). In both cases, the transgene is transmitted to the F2 generation. In addition, high-resolution FISH analysis of transgenic F1s reveals that the use of NLS increases the number of distinct transgene integration sites along chromatin fibres.


Moral structuring of children during the process of obtaining informed consent in clinical and research settings.
Informed consent is an important factor in a child's moral structure from which different types of doctor-patient relationships arise. Children's autonomy is currently under discussion in terms of their decent treatment, beyond what doctors and researchers perceive. To describe the influential practices that exist among clinicians and researchers toward children with chronic diseases during the process of obtaining informed consent. This was a cross-sectional, qualitative study via a subjective and interpretivist approach. The study was performed by conducting semi-structured interviews of 21 clinicians and researchers. Data analysis was performed using the SPSS version 21® and Atlas Ti version 7.0® programs. The deliberative and paternalistic models were influential practices in the physician-patient relationship. In the deliberative model, the child is expected to have a moral awareness of their care. The paternalistic model determined that submission was a way of structuring the child because he or she is considered to be a subject of extreme care. The differentiated objectification [educational] process recognizes the internal and external elements of the child. Informed consent proved to be an appropriate means for strengthening moral and structuring the child.


Interleukin 12 protects from a T helper type 1-mediated autoimmune disease, experimental autoimmune uveitis, through a mechanism involving interferon gamma, nitric oxide, and apoptosis.
Pathogenic effector T cells in experimental autoimmune uveitis (EAU) are T helper type 1-like, and interleukin (IL)-12 is required for their generation and function. Therefore, we expected that IL-12 administration would have disease-enhancing effects. Mice were immunized with a uveitogenic regimen of the retinal antigen interphotoreceptor retinoid-binding protein, treated with IL-12 (100 ng/d for 5 d), and EAU was assessed by histopathology. Unexpectedly, IL-12 treatment failed to enhance EAU in resistant strains and downregulated disease in susceptible strains. Only treatment during the first, but not during the second, week after immunization was consistently protective. High levels of interferon gamma (IFN-gamma) were present in the serum during IL-12 treatment, but subsequent antigen-specific IFN-gamma production in protected mice was diminished, as were IL-5 production, lymph node cell proliferation, and serum antibody levels. Treated mice had fewer cells and evidence of enhanced apoptosis in the draining lymph nodes. Unlike wild-type mice, IFN-gamma-deficient, inducible nitric oxide synthase (iNOS)-deficient, and Bcl-2(lck) transgenic mice were poorly protected by IL-12, whereas IL-10-deficient mice were protected. We conclude that administration of IL-12 aborts disease by curtailing development of uveitogenic effector T cells. The data are compatible with the interpretation that IL-12 induces systemic hyperinduction of IFN-gamma, causing activation of iNOS and production of NO, which mediates protection at least in part by triggering Bcl-2 regulated apoptotic deletion of the antigen-specific T cells as they are being primed.


Investigation into the mechanism of (-)-epigallocatechin-3-gallate-induced precipitation of insulin.
The molecular interactions between EGCG and insulin were investigated to probe the mechanism of EGCG-induced insulin precipitation. The results indicated that 1-5mM EGCG induced insulin into reversible globular precipitates of 185-365 nm. The formation of precipitates was facilitated at high salt concentration and pH values close to insulin's isoelectric point, indicating that hydrophobic interaction was the main driving force. The precipitation was positively related to insulin concentration, but for EGCG, there was a suitable concentration (2 mM at 2 mg/mL of insulin) at which the precipitate content reached maximum. Mass spectroscopy analysis indicated that EGCG formed clusters in the aqueous solution and the clusters correlate with the insulin precipitation. Based on extensive investigation, a physical model was proposed to explain the molecular interactions between EGCG and insulin. Namely, EGCG monomers and clusters first bound to insulin dimers via hydrophobic interaction, leading to the reduction of the thickness of the hydration layer and the partial denaturation of insulin. Then, EGCG clusters acted as bridges to induce the aggregation and precipitation of insulin.


Can predation cause the 10-year hare cycle?
We relate causes of mortality of snowshoe hares to density of hares over an 8-year period that included a peak in numbers. We then use simulation modeling to examine whether these density-dependent relationships could produce changes in hare density similar to those observed in our study are in Yukon, Canada.Predation during winter was the largest source of mortality for snowshoe hares at Kluane, Yukon during 1978-84. There was a one-year lag in the response of winter predation mortality rate to hare density. There was a two-year lag in the response of winter mortality not caused by predators to hare density.A simple simulation model with density-dependent predation produced 8-11 year cycles only within a narrow range of parameters that are inconsistent with data from the Kluane region. However, a simulation model that predicted winter mortality rates using a delayed density-dependent numerical response and a Type II functional response by predators, produced 8-11 year cycles within the range of parameter values measured in our study. Yet another simulation model that predicted both summer and winter mortality rates using a delayed density-dependent numerical response and a Type II functional response by predators, did not produce 8-11 year cycles within the range of parameter values measured in our study. Lack of data on juvenile mortality may be one reason for this result.


Hepatitis B and hepatitis C virus infections: risk factors among drug users in Northwest England.
to identify the risk factors for hepatitis B (HBV) and hepatitis C (HCV) virus infections in drug users attending two drug treatment centres in Northwest England, and to evaluate the effect of both needle exchange and hepatitis B vaccination on the prevalence of hepatitis B and hepatitis C infections. a retrospective, cross-sectional study performed at the Regional Infectious Disease Unit and a Primary Care Centre for drug users in Liverpool. The study population included 773 drug users who had hepatitis serology performed between January 1992 and April 1996. Information on risk factors was obtained from clinical records; hepatitis serology data were obtained from the Liverpool Public Health Laboratory database. the overall seroprevalences of exposure markers for HBV (anti-HBc antibody) and HCV (anti-HCV antibody) were 48% and 67%, respectively. Duration of injecting drug use was the strongest predictor of HCV infection, with a crude odds ratio of 8.9 (95% confidence interval (CI): 4.5-17) for >10 compared to <3 years of injecting, and was also a strong predictor of HBV infection, with an adjusted odds ratio (controlled for the effects of HBV vaccination) of 5.7 (95% CI: 3.2-10) for >10 compared to <3 years' injecting. Vaccination against HBV was associated with greatly reduced HBV seroprevalence (crude odds ratio 0.11, 95% CI: 0.06-0.18). Overall, HCV was acquired earlier in the injecting career than HBV, but drug users who were not vaccinated against HBV acquired markers for HBV even more rapidly than for HCV. We found no independent protective effect for either anti-HBc or anti-HCV acquisition after the introduction of a needle-exchange scheme. hepatitis C is highly prevalent among Merseyside drug users and is likely to prove difficult to control because of rapid acquisition early in the injecting career. Vaccination against hepatitis B is the best means of protecting drug users from hepatitis B, and should be offered before injecting is commenced.


Cold-induced mitochondrial degradation and cryoprotectant synthesis in freeze-tolerant arctic caterpillars.
The larvae of Gynaephora groenlandica, a long-lived moth endemic to the high arctic, are perennially freeze-tolerant and able to increase their freeze-tolerance by synthesizing glycerol. Cold-induced mitochondrial changes were correlated (using electron microscopy, DNA staining, cytochrome c assay, and oxygen uptake) with glycerol production (using NMR spectroscopy) in larvae under different acclimations and in the field. Hypometabolism in summer- or warm-acclimated larvae led to glycerol accumulation. Extended exposure to near-zero or freezing temperatures caused mitochondrial degradation and glycerol accumulation. Rapid freezing of warm-acclimated larvae did not result in mitochondrial breakdown. Mitochondrial reconstitution upon warm-acclimation occurred much more rapidly (less than 1 week) than did degradation (greater than 2 months). Concomitant with mitochondrial breakdown was reduced oxidative metabolism, but the cytochrome c concentration remained independent of acclimation temperature. The adaptive response to cold by mitochondrial degradation and glycerol accumulation by G. groenlandica may be linked to diapause in other species of ectotherms.


"What is this strange sensation?" A qualitative exploration of metaphors used to verbalise hard-to-describe experiences by people with epilepsy.
Mental health comorbidities are frequent in epilepsy. Consequently, psychotherapy is becoming increasingly important. To address the psychological needs of people with epilepsy (PwE) it is essential to understand the subjective experiences of seizures better. There is little research on how people report seizures, and which psychological representations they have. We conducted a thematic analysis based on 42 (micro-phenomenological) interviews with 15 participants on their experiences of seizures. In these interviews, we identified three categories of seizure descriptions: (1) phenomena related to the body and emotions; (2) the moments that are difficult to describe; and (3) the use of figurative language and metaphors. Paroxysmal physical and psychological sensations were often reported spontaneously by the participants. The moments that were difficult to describe were expressed, among other things, through the use of paradoxes or the report of a 'strange' feeling and led participants to use figurative language. As these metaphors can reveal important information about people's subjective experiences, they were analyzed in detail. We identified the three main types of metaphors that the participants used most frequently: (1) perception, (2) nature, and (3) battle. The theme of battle was most frequently used in different forms and was closely related to the metaphors from the fields of perception and nature, thus representing a key point in the personal experience of seizures. These findings can contribute to developing psychotherapeutic approaches for the treatment of seizure disorders.


Effects of slice selection and diffusion on T2 measurement.
This study examines slice selection and diffusion as sources of systematic error in T2 estimates obtained from imaging experiments. The selective refocusing pulses in a multislice, two-echo, spin-warp experiment cause slice profiles of sequential echoes to change in shape. This results in bias in T2 images calculated from the two-echo data set. A method to correct the bias is presented. The effect of diffusion on T2 images obtained with typical two-echo imaging sequences was found to be negligible.


Interferon β-1a ring prophylaxis to reduce household transmission of SARS-CoV-2: a cluster randomised clinical trial.
Accumulating evidence indicates that an early, robust type 1 interferon (IFN) response to SARS-CoV-2 is important in determining COVID-19 outcomes, with an inadequate IFN response associated with disease severity. Our objective was to examine the prophylactic potential of IFN administration to limit viral transmission. A cluster randomised open label clinical trial was undertaken to determine the effects of pegylated IFNβ-1a administration on SARS-CoV-2 household transmission between December 3rd, 2020 and June 29th, 2021. Index cases were identified from databases of confirmed SARS-CoV-2 individuals in Santiago, Chile. Households were cluster randomised (stratified by household size and age of index cases) to receive 3 doses of 125 μg subcutaneous pegylated IFNβ-1a (172 households, 607 participants), or standard care (169 households, 565 participants). The statistical team was blinded to treatment assignment until the analysis plan was finalised. Analyses were undertaken to determine effects of treatment on viral shedding and viral transmission. Safety analyses included incidence and severity of adverse events in all treatment eligible participants in the standard care arm, or in the treatment arm with at least one dose administered. Clinicaltrials.gov identifier: NCT04552379. 5154 index cases were assessed for eligibility, 1372 index cases invited to participate, and 341 index cases and their household contacts (n = 831) enrolled. 1172 participants in 341 households underwent randomisation, with 607 assigned to receive IFNβ-1a and 565 to standard care. Based on intention to treat (ITT) and per protocol (PP) analyses for the primary endpoints, IFNβ-1a treatment did not affect duration of viral shedding in index cases (absolute risk reduction = -0.2%, 95% CI = -8.46% to 8.06%) and transmission of SARS-CoV-2 to household contacts (absolute risk reduction = 3.87%, 95% CI = -3.6% to 11.3%). Treatment with IFNβ-1a resulted in significantly more treatment-related adverse events, but no increase in overall adverse events or serious adverse events. Based upon the primary analyses, IFNβ-1a treatment did not affect duration of viral shedding or the probability of SARS-CoV-2 transmission to uninfected contacts within a household. Biogen PTY Ltd. Supply of interferon as 'Plegridy (peginterferon beta-1a).' The study was substantially funded by BHP Holdings Pty Ltd.


NETs biomarkers in saliva and serum OSCC patients: One hypothesis, two conclusions.
The actual role of neutrophils and neutrophil extracellular traps (NETs) in the course of cancer has not been clearly defined. The aim of this study was to determine the clinical usefulness of NETs biomarkers in saliva in confrontation with the blood serum and tumor tissue as a potential prognostic and therapeutic target in patients with oral squamous cell carcinoma (OSCC). Expression of myeloperoxidase (MPO), and histones H2A, H2B, H3 in the tumor tissue, was investigated using immunohistochemistry. The expression of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase subunits: p47-phox, p67-phox (neutrophil cytosolic factor 2, NCF2) and panRac, as well as citrullinated histone H3 (CitH3) in peripheral blood neutrophil lysates, was assessed via Western blot. ELISA tests were employed to measure the concentrations of circulating free DNA (cfDNA) and MPO in saliva only, and NOX1, NCF2, DNASE1 in saliva and serum. Extracellular expression of MPO and histones was localized within tumor tissue. Significantly lower expression of p67-phox, panRac, and CitH3 was determined in OSCC patients. Considerably lower concentrations of NOX1, NCF2, and DNASE1 in the saliva samples of cancer patients were observed. However, the levels of NOX1, NCF2, and DNASE1 in the serum of patients with cancer were substantially higher. The results obtained from the saliva of cancer patients suggest an impairment of the immunological homeostasis within the oral cavity related to NET formation, the causes of which should be sought in deficient activation of NADPH oxidase.


Silver speciation and characterization of nanoparticles released from plastic food containers by single particle ICPMS.
Silver migration from a commercial baby feeding bottle and a food box containing AgNPs, as confirmed by SEM-EDX analysis, was evaluated using food simulant solutions [i.e., water, 3% (v/v) acetic acid, and 10% and 90% (v/v) ethanol]. Silver release was investigated at temperatures in the 20-70°C range using contact times of up to 10 days. Migration of silver from the food box was in all cases 2 to 3 orders of magnitude higher than that observed for the baby bottle, although the total silver content in the original box material was half of that found in the baby bottle. As expected, for both food containers, silver migration depended on both the nature of the tested solution and the applied conditions. The highest release was observed for 3% acetic acid at 70°C for 2h, corresponding to 62ngdm(2) and 1887ngdm(-2) of silver for the baby bottle and the food box, respectively. Single particle-inductively coupled plasma mass spectrometry (SP-ICPMS) was used to characterise and quantify AgNPs in the food simulants extracts. Sample preparation was optimized to preserve AgNPs integrity. The experimental parameters affecting AgNPs detection, sizing and quantification by SP-ICPMS were also optimised. Analyses of water and acidic extracts revealed the presence of both dissolved silver and AgNPs. Small AgNPs (in the 18-30nm range) and particle number concentrations within the 4-1510 10(6)L(-1) range were detected, corresponding to only 0.1-8.6% of the total silver released from these materials. The only exception was AgNPs migrated into water at 40°C and 70°C from the food box, which accounted for as much as 34% and 69% of the total silver content, respectively.


Characterization and application of strong ion-exchange membrane adsorbers as stationary phases in high-performance liquid chromatography of proteins.
Filtration membranes carrying strong cation- or anion-exchange groups on their surface were evaluated for their potential as membrane adsorber stationary phases in the high-performance liquid chromatography of proteins. The membranes are commercially available and can be obtained inserted into ready-to-use filter holders. Owing to their thinness (170-190 microns), the pressure drop of the membranes is extremely low. Flow-rates of up to 65 ml min-1 per unit became thus possible. The low pressure drop of a single membrane layer also permitted an effortless scaling up, as a stack of several membranes or filter units could be used, if necessary. Sample distribution, protein binding capacity, elution conditions, separation efficiency and recovery were investigated as a function of the flow-rate. The time required for the separation of certain protein mixtures could be reduced to less than 1 min. Appropriate conditions were defined for the separation of human serum and for the isolation of subtilisin Carlsberg and beta-galactosidase from cell culture supernatants.


Reaction dynamics of H(3)(+) + CO on an interpolated potential energy surface.
An accurate potential energy surface for H(3)(+) + CO has been constructed by interpolation of ab initio data. The reaction cross sections and thermal rate coefficients for the production of HCO(+) and HOC(+) have been evaluated using quasiclassical trajectory simulations.


Vitamin D-regulated, ATP-dependent calcium transport by intestinal Golgi vesicles during maturation in the rat.
The developmental aspects of calcium uptake by intestinal Golgi vesicles was determined using highly purified Golgi vesicles from enterocytes of suckling (2 wk old), weanling (3 wk old), and adolescent (6 wk old) rats. Calcium uptake by Golgi vesicles at all age groups represented transport into the intravesicular space as evident by temperature dependency and by calcium ionophore A23187-induced calcium efflux studies. Calcium uptake was driven by ATP at all age groups, however, maximal uptake at 15 min was significantly greater in Golgi vesicles of adolescent rats compared to mean values in Golgi vesicles of suckling rats (p less than 0.01). Calcium uptake in the absence of ATP was minimal. The requirement for the adenine base and the hydrolysis of the beta-gamma-phosphodiester was tested by replacement of ATP in the incubation media by CTP and the nonhydrolyzable ATP analogue, adenylyl-(beta-gamma-methylendiphosphonate). Both agents had no stimulatory effect on calcium uptake. Calcium uptake was linear up to 40 s. Kinetic parameters of calcium uptake at free calcium concentrations of 0.04 to 1.0 microM showed a maximal transport capacity of 0.99 +/- 0.05, 0.55 +/- 0.04, and 0.29 +/- 0.03 nmol/mg protein/15 s for adolescent, weanling, and suckling rats, respectively. Km values were 0.16 +/- 0.02, 0.12 +/- 0.03, and 0.07 +/- 0.02 microM for adolescent, weanling and suckling rats, respectively. Km and Vmax values were significantly different between adolescent and suckling rats (p less than 0.01). The calcium regulatory protein calmodulin has no effect on calcium uptake by Golgi vesicles. Vitamin D deficiency in all age groups decreased ATP-dependent calcium uptake. Administration of 1,25-(OH)2 vitamin D3 8 h before death enhanced ATP-dependent calcium uptake in all age groups studied. This enhancement was the result of increase in maximal transport capacity of ATP-dependent calcium uptake. This study demonstrates a vitamin D-regulated ATP-driven calcium uptake by intestinal Golgi vesicles at all age groups including the suckling period. This transport system shows developmental patterns in regard to its kinetic parameters.


Transcription of the dystrophin gene in human muscle and non-muscle tissue.
The gene that is defective in patients with Duchenne and Becker muscular dystrophy consists of about 60 short exons scattered along a gigantic DNA region that spans some 2 megabase pairs. The encoded protein, dystrophin, was recently characterized as a component of muscle intracellular membranes of low abundance. The dystrophin messenger RNA is difficult to study in both normal and pathological tissue specimens because it is large (14 kilobases) and scarce (0.01-0.001% of total muscle mRNA). We report here that efficient in vitro co-amplifications of the mRNAs of the dystrophin gene and of a reporter gene, aldolase A, by the polymerase chain reaction procedure enables us to obtain a quantitative estimate of the dystrophin gene transcript. A processed, transcribed segment was thus detected in 13 different human tissues. It ranged from 0.02-0.12% of total mRNA in skeletal muscle to 25,000 times less in lymphoblastoid cells.


Cutaneous manifestations of the acquired immunodeficiency syndrome in children.
The acquired immunodeficiency syndrome (AIDS) in children is now known to be a clinical entity separate and distinct from AIDS in adults. In this article we present a review of the recent literature describing the history, definitions, epidemiology, differential diagnosis, and immunologic and clinical features of pediatric AIDS. Special emphasis is placed on the cutaneous manifestations of human immunodeficiency virus infection in children, which, to date, have not been the subject of a comprehensive review.


Reduced risk of secondary primary extra pulmonary cancer in advanced/metastatic lung cancer patients treated with immune checkpoint inhibitors.
Lung cancer survivors are at high risk of developing a second primary cancer (SPC). We explored the Unicancer Epidemiology Strategy Medical-Economics for advanced or metastatic lung cancer (AMLC) database to assess the impact of immune checkpoint inhibitors (ICI) on the risk of SPC in patients with advanced/metastatic lung cancer. This retrospective study used data from patients with AMLC, with treatment initiated between January 1st 2015 and December 31st 2018. Patients with lung cancer as the second primary cancer were excluded and a 6-months landmark threshold was applied to exclude patients with synchronous SPC, patients dead without SPC or with a follow-up inferior to 6 months. A propensity score (PS) was calculated on the following baseline covariates: Age at locally advanced or metastatic diagnosis, sex, smoking status, metastatic status, performance status and histological type. The inverse probability of treatment weighting approach was used on the analyses aiming to assess the impact of ICI administered for AMLC, on the risk of occurrence of SPC. Among the 10 796 patients, 148 (1.4%) patients had a diagnosis of SPC in a median interval of 22 (min-max: 7-173) months. All the patients (100%) with locally advanced or metastatic LC received at least one systemic treatment including (chemotherapy regimen (n = 9 851, 91.2%); ICI (n = 4 648, 43.0%); targeted treatment (n = 3 500; 32.4%). 40 (0.9%) SPC were reported in the 4 648 patients with metastatic LC treated with ICI vs 108 (1.7%) out of the 6 148 who did not receive immunotherapy (p < 0.0001). The multivariate analysis identified that treatment with ICI in patients with AMLC is associated with a reduced risk of SPC (HR = 0.40, 95% CI 0.27-0.58). Treatment with ICI in AMLC patients was associated with a significantly reduced risk of SPC. Prospective studies are required to confirm these results.


Forensics: age written in teeth by nuclear tests.
Establishing the age at death of individuals is an important step in their identification and can be done with high precision up to adolescence by analysis of dentition, but it is more difficult in adults. Here we show that the amount of radiocarbon present in tooth enamel as a result of nuclear bomb testing during 1955-63 is a remarkably accurate indicator of when a person was born. Age is determined to within 1.6 years, whereas the commonly used morphological evaluation of skeletal remains and tooth wear is sensitive to within 5-10 years in adults.


Association of normal systolic blood pressure in the emergency department with higher in-hospital mortality among hypertensive patients.
Blood pressure is commonly elevated at the hospital emergency department (ED), especially among hypertensive patients. The aim of the study was to determine the association between ED systolic blood pressure (SBP) and in-hospital mortality among hypertensive patients. The authors retrospectively retrieved records of hypertensive patients who were hospitalized during a seven-year period. The authors examined the association between SBP and in-hospital mortality rate, adjusted for demographics, heart rate, comorbidities, laboratory results, and hospital ward. Overall, 96 423 patients were included. Compared to patients with SBP 110-139 mm Hg, the adjusted odds ratios were 4.1 (95% CI, 3.7-4.6) with SBP <90, 1.6 (95% CI, 1.4-1.7) with SBP 90-109, 0.7 (95% CI, 0.6-0.7) with SBP 140-159, 0.7 (95% CI, 0.6-0.7) with SBP 160-179, 0.7 (95% CI, 0.6-0.8) with SBP 180-199, 0.9 (95% CI, 0.7-1.1) with SBP 200-219, and 1.1 (95% CI, 0.7-1.7) with SBP ≥220 mm Hg. Thus, SBP levels of 110-139 mm Hg were associated with higher in-hospital mortality in comparison with elevated SBP up to 200 mm Hg.


Effect of ultrasound parameters of benign thyroid nodules on radiofrequency ablation efficacy.
Ultrasound-guided radiofrequency ablation (RFA) is a minimally invasive therapy for thyroid nodules (TNs). Understanding the determinants of RFA efficacy can improve treatment and prognosis. This study aims to investigate the relationship between ultrasound parameters of benign TNs and the efficacy of RFA. A pretest-posttest interventional study was conducted in 2021 on 250 randomly sampled patients with benign TNs, receiving RFA. For this purpose, the volume reduction (VR) and the VR ratio (VRR) of the nodules were measured at the 1-, 3-, 6-, and 12-month follow-up periods after the RFA completion. The technical success rate (TSR) of this procedure was then categorized into four states, including low (VRR < 25%), moderate (VRR = 25-49%), high (VRR = 50-74%), and very high (VRR ≥ 75). Ordered logistic regression (OLR) was further utilized to investigate the effect of the ultrasound parameters of TNs on the TSR. The analyses were notably performed using Stata 14.2. The VRR at the 1-, 3-, 6-, and 12-month follow-up periods were 38.7%, 53.6%, 59.3%, and 59.9%, respectively. The mean VR was also statistically significant at all follow-ups (p < 0.001). At the 1-, 3-, and 6-month follow-up periods, the VR of over 50% was observed in 28.2%, 52.1%, and 65.2% of the nodules, respectively. The odds ratios (ORs) of the RFA success were found to be 4.3 times higher for the nodules in the left lobe compared to the right lobe (OR: 4.31, p = 0.002), 6.3 times greater for isoechoic nodules compared to hyperechoic nodules (OR: 6.39, p < 0.001), 6.2 times higher for hyper-vascular nodules compared to hypo-vascular nodules (OR: 6.25, p = 0.005), and 2.3 times greater for mixed nodules compared to solid ones (OR: 2.37, p = 0.049). The ultrasound parameters of TNs had a statistically significant effect on the efficacy of RFA. Small-sized, isoechoic, and hyper-vascular nodules, as well as those with mixed tissue, were observed to respond better to RFA, leading to a better prognosis in terms of VR after treatment.


[Role of the genetic-physiological interrelationships of mother-progeny in establishing the viability and fertility of mammals. II. The weight of the embryos of BALB, CBA and DBA strain mice developing from transplanted blastocysts].
The weights of embryos and their placentas obtained by blastocysts of CBA/LacY and DBA/2 mouse strains transfer in recipient females of BALB/c strain and also by blastocysts of BALB/c mouse strain transfer in recipient females of CBA/LacY strain were analysed on the 16th gestation day. It is shown that placental weights are determined by genotypic peculiarities of embryos, although comparative placental weights of different strain embryos could also depend on females fertility. The weight of allogenic embryos (developed from transferred blastocysts) significantly excessed the weight of singenic embryos, and most significant differences were noted in females with small number of embryos. The possibilities to solve some applied and fundamental problems of mammalian reproduction given by the method of interstrain and interbreed early stage embryos transfer are discussed.


Flexor tenosynovial fistulas in the palm.
Tenosynovial fistulas in the palm are rare. If conservative treatment is unsuccessful, surgical treatment may include excision of the fistula and local flap coverage. In this article, I report 15 patients who were surgically treated for tenosynovial fistulas in the palm. Between 1996 and 2009, I treated 15 patients for tenosynovial fistulas in the palm. There were 9 women and 6 men, with an average age of 42 years (range, 21-63 y). The index finger was involved in 5 patients, the long finger in 7, and the ring finger in 3. One patient had a fish fin injury, 6 had multiple surgeries for release of stenosing flexor tenosynovitis with intraoperative steroid injections, 1 had a pellet gun injury, and 7 had lacerations in the distal palm. Four patients had had unsuccessful closure of the fistula. All patients presented with a distal palm sinus draining clear frothy fluid. There were no signs of infection. Gram stains and cultures were negative. Smear and culture for Mycobacterium marinum were negative in the patient who had the fish fin injury. I tried conservative treatment in all patients for an average of 7 weeks. All patients were treated with excision of the sinus tract with partial resection of the A1 pulley and soft tissue coverage with a transposition flap. Pathological examination revealed epithelialization with nonspecific chronic inflammation. Postoperative follow-up averaged 59 months (range, 6-148 mo). All fistulas healed. Patients regained full range of motion and normal grip and pinch strength. One patient had transient tenderness of the scar for 3 months. There were no recurrences. Tenosynovial fistulas may develop after an injury to the flexor tendon sheath or following the use of steroids after release of trigger fingers recurring after an initial surgical release. Surgical treatment with excision of the fistula and local flap coverage yields excellent results. Therapeutic IV.


The wettability of polytetrafluoroethylene and polymethyl methacrylate by aqueous solution of two cationic surfactants mixture.
Advancing contact angle (theta) measurements were carried out for aqueous solutions of cetyltrimethylammonium bromide (CTAB) and cetylpyridinium bromide (CPyB) mixtures on polytetrafluoroethylene (PTFE) and polymethyl methacrylate (PMMA). The obtained results indicate that the wettability of PTFE and PMMA by aqueous solutions of CTAB and CPyB mixtures depends on the composition and concentration of the mixture; however, synergism in the wettability does not exist. In the range of low concentrations of aqueous solution mixtures there is a linear dependence between the contact angle and composition of the mixtures, but at a concentration close to CMC a deviation from linear dependence is observed. In contrast to Zisman, there is no linear dependence between costheta and the surface tension of aqueous solution of CTAB and CPyB mixtures, but a linear dependence exists between the adhesional and surface tension, and these lines have a slope -1 and -0.34 for PTFE and PMMA, respectively, which suggests that adsorption of CTAB and CPyB mixtures at water-air and PTFE-water is the same, and the orientation of the CTAB and CPyB molecules at both interfaces in the saturated monolayer should also be the same. Adsorption of these mixtures at water-air interface is considerably higher than at PMMA-water interface, and CTAB and CPyB molecules should be parallelly oriented to PMMA surface in the saturated monolayer. Extrapolation of the straight lines to the points corresponding to the surface tension of aqueous solution, which completely spreads over the PTFE and PMMA surface, gives a critical surface tension of wetting equal to 23.44 and 33.13 mN/m, respectively. The value of 23.44 mN/m is higher than that of the surface tension of PTFE, but the value of 33.13 is lower than that of Lifshitz-van der Waals components of PMMA surface tension. On the basis of the critical surface tension, the surface tension of PTFE and PMMA, the Young equation, and thermodynamic analysis of the adhesion work of aqueous solution of surfactant to polymer surface, it was found that for PTFE and PMMA the changes of the contact angle of aqueous solution of two cationic surfactants mixtures on their surfaces as a function of the solution concentration resulted only from the decrease of the polar component of the solution surface tension.


Deep learning-assisted model-based off-resonance correction for non-Cartesian SWI.
Patient-induced inhomogeneities in the static magnetic field cause distortions and blurring (off-resonance artifacts) during acquisitions with long readouts such as in SWI. Conventional versatile correction methods based on extended Fourier models are too slow for clinical practice in computationally demanding cases such as 3D high-resolution non-Cartesian multi-coil acquisitions. Most reconstruction methods can be accelerated when performing off-resonance correction by reducing the number of iterations, compressed coils, and correction components. Recent state-of-the-art unrolled deep learning architectures could help but are generally not adapted to corrupted measurements as they rely on the standard Fourier operator in the data consistency term. The combination of correction models and neural networks is therefore necessary to reduce reconstruction times. Hybrid pipelines using UNets were trained stack-by-stack over 99 SWI 3D SPARKLING 20-fold accelerated acquisitions at 0.6 mm isotropic resolution using different off-resonance correction methods. Target images were obtained using slow model-based corrections based on self-estimated Δ B 0 $$ \Delta {B}_0 $$ field maps. The proposed strategies, tested over 11 volumes, are compared to model-only and network-only pipelines. The proposed hybrid pipelines achieved scores competing with two to three times slower baseline methods, and neural networks were observed to contribute both as pre-conditioner and through inter-iteration memory by allowing more degrees of freedom over the model design. A combination of model-based and network-based off-resonance correction was proposed to significantly accelerate conventional methods. Different promising synergies were observed between acceleration factors (iterations, coils, correction) and model/network that could be expanded in the future.


Clinical phenomenology of dystonia.
Dystonia is defined as a motor syndrome characterized by sustained muscle contractions, usually producing twisting and repetitive movements or abnormal postures. Dystonia can be present at rest or worsened by action. Dystonia is commonly classified according to age at onset (childhood, adolescent type, and adult type), etiology (idiopathic, and symptomatic), and distribution (focal dystonia, segmental dystonia, generalized dystonia, multifocal dystonia and hemidystonia). The different subtypes of focal and segmental dystonias may have different clinical features. Neuropsychiatric disorders may be present in dystonia.


Effects of raw and heat-treated bambara groundnut (Vigna subterranea) on the performance and body composition of growing broiler chicks.
Bambara groundnut (Vigna subterannea)--a leguminous root nut, which grows in the tropics and subtropics--was used in an experiment to test its effect on the performance of growing broiler chicks. Performance was measured by monitoring growth, measuring nutrients and energy balances and also by determining nutrient accretion. Twelve-day old broiler chicks, kept in individual metabolic cages, were used in an experiment in which birds were equally allotted (n = 10) into a control (fed high performance diet made up principally of wheat and soybean meal) and 6 test groups fed diets containing 19, 76 and 95% raw or autoclaved bambara groundnuts. All diets were similar in energy, nitrogen and total lipid contents. Diets were also balanced for amino acids, vitamins and minerals in accordance to the specific requirements of the birds. Feed and water were provided ad libitum. Growth performance was monitored over 15 days. Nutrient and energy balances were measured by use of TiO2 as marker. The comparative slaughter technique was implored for the determination of energy and nutrient accretion. The results showed that the level of raw or autoclaved bambara had no significant influence on feed intake. Increasing the bambara level in the diets caused a general linear drop in the performance of the broilers. However, with up to 95% bambara in the diet, the general performance was still above 75% compared to the control. Increasing levels of bambara groundnut caused a decrease in the metabolizability of energy and efficiency of utilisation of ME for BWG. The animals retained more water with increasing levels of raw bambara in the diets while autoclaving increased their DM content to levels comparable to the control. The protein composition of gain was comparable at all levels of inclusion. In general autoclaving improved the performance of bambara.


The psychiatric and social characteristics of patients with functional dysphonia.
Of 121 consecutive outpatients seen in an ENT clinic who received a diagnosis of functional dysphonia, 71 who were referred to the speech therapy department were interviewed. Sixty one (86%) were women, and the mean age of the group was 47.6 yr. The commonest voice disorder was huskiness or hoarseness, and only five patients had a pure 'whispering' dysphonia. There was little evidence of major psychiatric disorder in the group: eight patients had a past psychiatric history; two had histrionic personality disorder, and 22 (33%) had clinically diagnosable mood disorders which were mainly anxiety/tension states. This descriptive study formed the background for an investigation of the psychosocial stressors preceding onset of functional dysphonia.


Training on motor and visual spatial learning tasks in early adulthood produces large changes in dendritic organization of prefrontal cortex and nucleus accumbens in rats given nicotine prenatally.
Experience-dependent plasticity is an ongoing process that can be observed and measured at multiple levels. The first goal of this study was to examine the effects of prenatal nicotine on the performance of rats in three behavioral tasks (elevated plus maze (EPM), Morris water task (MWT), and Whishaw tray reaching). The second goal of this experiment sought to examine changes in dendritic organization following exposure to the behavioral training paradigm and/or low doses of prenatal nicotine. Female Long-Evans rats were administered daily injections of nicotine for the duration of pregnancy and their pups underwent a regimen of behavioral training in early adulthood (EPM, MWT, and Whishaw tray reaching). All offspring exposed to nicotine prenatally exhibited substantial increases in anxiety. Male offspring also showed increased efficiency in the Whishaw tray-reaching task and performed differently than the other groups in the probe trial of the MWT. Using Golgi-Cox staining we examined the dendritic organization of the medial and orbital prefrontal cortex as well as the nucleus accumbens. Participation in the behavioral training paradigm was associated with dramatic reorganization of dendritic morphology and spine density in all brain regions examined. Although both treatments (behavior training and prenatal nicotine exposure) markedly altered dendritic organization, the effects of the behavioral experience were much larger than those of the prenatal drug exposure, and in some cases interacted with the drug effects.


Analysis of risk factors affecting long-term survival in elderly patients with advanced gastric cancer.
Factors predicting postoperative complications after gastrectomy for elderly patients with gastric cancer have been analyzed in several previous studies. However, there is limited research available on risk factors related to long-term survival. This study aimed to analyze factors affecting long-term survival after curative gastrectomy in elderly patients with advanced gastric cancer. This study included patients aged > 75 years with histologically confirmed advanced gastric cancer stage II or greater. Before analysis, risk factors were categorized into four groups: baseline characteristics, underlying diseases, surgical and pathologic factors, and nutritional factors. The mean follow-up duration was 71.0 months. The 5-year overall survival and disease-specific survival rates were 51.5% and 58.3%, respectively. Kaplan-Meier curves showed that patients who were female and overweight had significantly longer survival rates than those who were male and underweight. Elderly patients who underwent a total gastrectomy had poorer survival rates than those who underwent a distal gastrectomy. Multivariate analysis demonstrated that tumor stage, extent of gastrectomy, overweight status and overall complication were independent risk factors for overall survival. Our study show that the overweight patients, the extent of gastrectomy, tumor stage and overall complications are significant risk factors affecting long-term survival. Therefore, surgeons may be cautious in performing total gastrectomy in elderly gastric cancer patients. Additionally, it is important to focus on improving nutritional status and mitigating overall complications.


15d-Prostaglandin J2 activates peroxisome proliferator-activated receptor-gamma, promotes expression of catalase, and reduces inflammation, behavioral dysfunction, and neuronal loss after intracerebral hemorrhage in rats.
Peroxisome proliferator-activated receptor-gamma (PPARgamma) is a transcription factor that regulates the expression of various gene products that are essential in lipid and glucose metabolism, as well as that of the peroxisome-enriched antioxidant enzyme, catalase. Activation of PPARgamma is linked to anti-inflammatory activities and is beneficial for cardiovascular diseases. However, little is known about its role in intracerebral hemorrhage (ICH). 15-Deoxy-Delta(12,14)-prostaglandin J2 (15d-PGJ2) acts as a physiologic agonist for PPARgamma. In this study, we found that injection of 15d-PGJ2 into the locus of striatal hematoma increased PPARgamma-deoxyribonucleic acid (DNA) binding activity and the expression of catalase messenger ribonucleic acid (mRNA) and protein in the perihemorrhagic area. Additionally, 15d-PGJ2 significantly reduced nuclear factor-kappaB (NF-kappaB) activation and prevented neutrophil infiltration measured by myeloperoxidase (MPO) immunoassay, and also reduced cell apoptosis measured by terminal deoxynucleotide transferase dUTP nick-end labeling (TUNEL). In addition, 15d-PGJ2 reduced behavioral dysfunction produced by the ICH. Altogether, our findings indicate that injection of 15d-PGJ2 at the onset of ICH is associated with activation of PPARgamma and elevation of catalase expression, suppression of NF-kappaB activity, and restricted neutrophil infiltration. All these events predicted reduced behavioral deficit and neuronal damage.


Effects of DNA- and Mycobacterium bovis BCG-based delivery of the Flt3 ligand on protective immunity to Mycobacterium tuberculosis.
The control of intracellular pathogens such as Mycobacterium tuberculosis is dependent on the activation and maintenance of pathogen-reactive T cells. Dendritic cells (DCs) are the major antigen-presenting cells initiating antimycobacterial T-cell responses in vivo. To investigate if immunization strategies that aim to optimize DC function can improve protective immunity against virulent mycobacterial infection, we exploited the ability of the hematopoietic growth factor Fms-like tyrosine kinase 3 ligand (Flt3L) to expand the number of DCs in vivo. A DNA fusion of the genes encoding murine Flt3L and M. tuberculosis antigen 85B stimulated enhanced gamma interferon (IFN-gamma) release by T cells and provided better protection against virulent M. tuberculosis than DNA encoding the single components. Vaccination of mice with a recombinant Mycobacterium bovis BCG strain secreting Flt3L (BCG:Flt3L) led to early expansion of DCs compared to immunization with BCG alone, and this effect was associated with increased stimulation of BCG-reactive IFN-gamma-secreting T cells. BCG and BCG:Flt3L provided similar protective efficacies against low-dose aerosol M. tuberculosis; however, immunization of immunodeficient mice revealed that BCG:Flt3L was markedly less virulent than conventional BCG. These results demonstrate the potential of in vivo targeting of DCs to improve antimycobacterial vaccine efficacy.


Investigation of ion-pair precipitates of selected alkoxylates and complex salts of specific metal cations by liquid secondary ion mass spectrometry.
Liquid secondary ion (LSI) mass spectra of ion-pair precipitates obtained for Triton X-100 with strontium, lead, cadmium and mercury tetraphenylborates and for selected butoxylene-ethoxylene monoalkyl ethers with barium tetraiodobismuthate(III) are discussed. On the basis of LSI mass spectra, recorded in both positive and negative modes, the formulae of the ion-pair precipitates were determined. On the basis of B/E mass spectra, the fragmentation routes of [M - H + Ba](+) ions for butoxylene-ethoxylene monoalkyl ether complexes of barium and [M - H + Cd](+) ions for the Triton X-100 complex of cadmium are proposed.


Synergistic regulation of microglia differentiation by CD93 and integrin β1 in the rat pneumococcal meningitis model.
Streptococcus pneumoniae is the main bacterial pathogen of meningitis worldwide, which has a high mortality rate and survivors are prone to central nervous system (CNS) sequelae. In this regard, microglia activation has been associated with injury to the CNS. The aim of this study was to investigate the relationship between CD93, integrin β1, and microglia activation. In the rat pneumococcal meningitis model, we found significant increases of CD93 and integrin β1 expression and differentiation of M1 phenotype microglia. Furthermore, we showed in vitro siRNA-mediated downregulation of CD93 and integrin β1 expression after infecting highly aggressive proliferating immortalized (HAPI) microglia cells with S. pneumoniae. We observed differentiation of S. pneumonia-infected HAPI microglia cells to the M1 phenotype and significant release of soluble CD93 (sCD93) and integrin β1 expression. Complement C1q and metalloproteinases promoted sCD93 release. We also showed that downregulation of CD93 significantly reduced differentiation to M1 microglia and increased differentiation to M2 microglia. However, addition of recombinant CD93 may regulate microglia differentiation to the M1 phenotype. Furthermore, the downregulation of integrin β1 resulted in downregulation of the CD93 protein. In conclusion, interaction between integrin β1 and CD93 promotes differentiation of microglia to the M1 phenotype, increases the release of pro-inflammatory factors, and leads to nervous system injury in pneumococcal meningitis.


Application of the EPR spin-trapping technique to the detection of radicals produced in vivo during inhalation exposure of rats to ozone.
Ozone is known to induce lipid peroxidation of lung tissue, although no direct evidence of free radical formation has been reported. We have used the electron paramagnetic resonance (EPR) spin-trapping technique to search for free radicals produced in vivo by ozone exposure. The spin trap alpha-(4-pyridyl-1-oxide)-N-tert-butylnitrone (4-POBN) was administered ip to male Sprague-Dawley rats. The rats were then exposed for 2 hr to either 0, 0.5, 1.0, 1.5, or 2.0 ppm ozone with 8% CO2 to increase their respiratory rate. A six-line 4-POBN/radical spin adduct signal (aN = 15.02 G and a beta H = 3.27 G) was detected by EPR spectroscopy in lipid extracts from lungs of rats treated with 4-POBN and then exposed to ozone. Only a weak signal was observed in the corresponding solution from rats exposed to 0 ppm ozone (air with CO2 only). The concentration of the radical adduct increased as a function of ozone concentration. After administration of 4-POBN, rats were exposed for either 0.5, 1.0, 2.0, or 4.0 hr to either 0 or 2.0 ppm ozone (with CO2). The radical adduct concentration of the ozone-exposed groups at exposure times of 2.0 and 4.0 hr was significantly different from that of the corresponding air control groups. A correlation was observed between the radical adduct concentration and the lung weight/body weight ratio. These results demonstrate that ozone induces the production of free radicals in rat lungs during inhalation exposure and that radical production may be involved in the induction of pulmonary toxicity by ozone. This is the first direct evidence for ozone-induced free radical production in vivo.


Effect of moderate-intensity seated exercise on the management of metabolic outcomes in hypertensive individuals with or without exercise habits.
We aimed to evaluate the effect of moderate-intensity seated exercise on metabolic outcomes in hypertensive individuals with or without exercise habits. Forty-two hypertensive individuals volunteered for this study and were classified into 3 groups by their habits and place for moderate-intensity exercise prior to this study: NONE (<2 days/week or no exercise; n = 13), HOME (≥30 min/day and ≥2 days/week at home; n = 15), and GYM (≥30 min/day and ≥2 days/week at a hospital gym; n = 14). They performed their daily activities as usual and seated exercise (stepping and stepping with trunk rotation; a range of 11-13 on the Borg rating of perceived exertion scale) for at least 15 min/day and at least 3 days/week for 12 weeks. Thirty-five participants (age: 67.7 ± 5.9 years) completed the study, and there was no difference among the 3 groups regarding weekly exercise. The homeostasis model assessment of insulin resistance (HOMA-IR) value in the NONE group was significantly higher than that in the GYM group at baseline (p < 0.05), but it decreased significantly after 12 weeks (from 2.2 ± 0.8 to 1.7 ± 0.7, p < 0.05). Changes in HOMA-IR in the NONE group after 12 weeks was greater than that in the HOME and GYM groups (both p < 0.01). The HOME and GYM groups showed no significant changes in any of the variables. Moderate-intensity seated exercise may be an effective strategy to improve insulin resistance in hypertensive individuals without exercise habits.