Beneficial effects of acetylsalicylic acid (aspirin) on the actions of extracellular vesicles shed by Trypanosoma cruzi in macrophages.
Trypomastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease, shed extracellular vesicles (EVs) that promote the susceptibility of host cells to infection. During T. cruzi infection, the immune response of the host is important for controlling parasitism, which is necessary for survival. Macrophages produce inflammatory mediators, such as eicosanoids and nitric oxide (NO), with trypanocidal effects that control the parasite load in the early stages of the disease. In this study, we evaluated the contribution of host cyclooxygenase (COX) to the actions of EVs shed by T. cruzi strain Y (EVs-Y) in infected macrophages. RAW 264.7 macrophages exposed to EVs-Y and then infected with trypomastigote forms of T. cruzi produced less NO, and an increased number of trypomastigote forms were internalized in the cell compared to the controls, indicating that the effects exerted by EVs-Y favor the parasite. Interestingly, when macrophages were pretreated with acetylsalicylic acid, a dual COX inhibitor, before exposure to EVs-Y and subsequent infection with trypomastigote forms, there was an increase in NO production and a decrease in trypomastigote uptake compared to the controls. These results suggest that EVs-Y modulates the macrophage response in favor of T. cruzi and indicate a role for COX in the effects of EVs.


Effects of antidepressant agents on the synthesis of brain monoamines.
The effect of seventeen established or possible antidepressant agents on the synthesis of 5-HT, noradrenaline and dopamine in rat brain has been investigated by measuring the accumulation of 5-hydroxytryptophan and DOPA induced by an inhibitor of the aromatic L-aminoacid decarboxylase (3-hydroxybenzylhydrazine hydrochloride, 100 mg/kg i.p.). All the established inhibitors of 5-HT, noradrenaline and dopamine uptake were found to inhibit the synthesis of the respective monoamines, presumably by influencing a receptor-mediated feedback mechanism. A close correlation appears to exist between blockade of transmitter uptake and inhibition of transmitter synthesis. The results support current ideas on the mode of action of antidepressant agents.


Physician factors as an indicator of technological device adoption.
This paper analyzes a sample interventional cardiologist's demographic, academic, and professional characteristics to provide an understanding of their technological device adoption styles. The study sample consisted of 15 physicians from two large Midwestern hospitals, one an academic medical center and the other a medium-sized community hospital. Interventional cardiologists were identified through their online physician profile and respective departments. A questionnaire was developed to assess each physician's self-perceived adoption style, their awareness of the new technology, their participation in clinical trials, organizational support, and how various factors influence their adoption of new technology. Lastly, a database of bare metal and drug eluting stents was examined to document the number of stents used by each physician. Pragmatic and observational findings are presented from the questionnaire, physician profile, to database on stent use. The paper concludes with a discussion of the managerial and forecasting implications and methods to promote technology adoption.


Evaluation of Socioeconomic Position and Survival After Out-of-Hospital Cardiac Arrest in Korea Using Structural Equation Modeling.
The association between low socioeconomic position (SEP) and poor survival after out-of-hospital cardiac arrest (OHCA) has not been thoroughly investigated. To evaluate the association between individual SEP and survival after OHCA and to identify any mediating pathways using structural equation modeling (SEM). This is a retrospective cohort study that used data collected from January 2013 to December 2019. Participants were adults with OHCA with a presumed cardiac etiology. The study was conducted in Korea, which has a universal health insurance system. Data were analyzed from January 2022 to February 2023. Individual SEP was measured by insurance type (National Health Insurance [NHI] and medical aid [MA]) and premiums. SEP was categorized into 5 groups, in which NHI beneficiaries were divided into quartiles (Q1, highest quartile; Q4, lowest quartile), and MA was the lowest SEP group. The primary outcome was survival to discharge. The association between SEP and OHCA survival was examined using multivariable logistic regression, and mediating factors were identified using SEM. A total of 121 516 patients (median [IQR] age, 73 [60-81] years; 43 912 [36.1%] female patients) were included. Compared with the NHI Q1 group, individuals with lower SEP had lower odds of survival to discharge. The adjusted odds ratios of survival to discharge were 0.97 (95% CI, 0.94-1.00), 0.88 (95% CI, 0.85-0.91), 0.91 (95% CI, 0.88-0.94), and 0.53 (95% CI, 0.50-0.56) for the NHI Q2, NHI Q3, NHI Q4, and MA groups, respectively. Several factors were found to mediate the association of SEP and survival in the total study population, with mediating proportions of 15.1% (95% CI, 11.8%-18.4%) for witnessed status, 4.8% (95% CI, 3.5%-6.0%) for bystander cardiopulmonary resuscitation provision, 41.8% (95% CI, 35.4%-48.1%) for initial rhythm, and 9.4% (95% CI, 7.4%-11.4%) for emergency department level. Among patients who survived to hospital admission, the mediation proportions were 11.8% (95% CI, 6.7%-16.9%) for witnessed status, 3.7% (95% CI, 1.3%-6.1%) for bystander cardiopulmonary resuscitation provision, 56.2% (95% CI, 41.0%-71.4%) for initial rhythm, 10.7% (95% CI, 6.1%-15.3%) for emergency department level, 20.2% (95% CI, 14.0%-26.5%) for coronary angiography, and 4.2% (95% CI, 2.2%-6.1%) for targeted temperature management. In this cohort study of patients with OHCA, lower individual SEP was significantly associated with lower survival to discharge. Potentially modifiable mediators can be targeted for public health interventions to reduce disparities in survival among patients with OHCA of different SEP.


Antiviral drugs 1983.
A number of antiviral compounds are currently available, and several others are of great interest. Trifluridine, idoxuridine, and vidarabine are effective topically in herpes simplex virus keratoconjunctivitis infection. Vidarabine (and presumably acyclovir) is effective in herpes simplex virus encephalitis and in herpes zoster infections in the immunocompromised host. Acyclovir is effective topically, orally, and intravenously in primary herpes genitalis, and the oral and intravenous forms are effective in recurrent herpes genitalis as well. Amantadine and rimantadine are effective prophylactically and therapeutically in influenza A infections. Ribavirin and interferon, although not licensed, are of great interest. Ribavirin may be useful in respiratory syncytial virus infections, and interferon may be of benefit in common colds and related disorders.


[Tuberculosis as a rare cause for an abdominal mass: report on three cases and review of the literature].
Here we present 3 patients with abdominal pain, weight loss and fever in combination with abdominal tumours which were all attributable to an ongoing mycobacterial infection. Worldwide, but especially in developing countries, tuberculosis is still an important cause of morbidity and death. In industrialised countries, however, tuberculosis is rarely considered as a differential diagnosis, especially when the primary lesion is not localised in the lung. Primary abdominal manifestations, in particular, are a frequent cause of delayed diagnosis due to the often elaborated necessary diagnostics. Once the diagnosis has been established, a combination therapy starting with isoniazid, rifampicin, pyrazinamide and ethambutol, i. e., the standard therapeutic regimen for pulmonary tuberculosis, is recommended. Concomitant diseases and atypical courses, however, often constitute serious challenges to the treating physician. Therefore, we here give a review of the literature and discuss three cases of abdominal tuberculosis with regard to clinical characteristics, diagnostic pitfalls and courses of disease.


Functional metabolic mapping of the rat brain during unilateral electrical stimulation of the subthalamic nucleus.
The alterations in local metabolic activity of several anatomically distinct brain areas were investigated by means of the quantitative autoradiographic 2-deoxy-D-[1-14C]glucose method in awake rats during unilateral electrical stimulation of the subthalamic nucleus (STH). Unilateral electrical stimulation of the STH induced local metabolic activation (by 70% as compared with the control group), as well as distal metabolic activations in the substantia nigra reticulata (by 34%), globus pallidus (by 19%), entopeduncular nucleus (by 18%), deep layers of the superior colliculi (by 15%), and parafascicular thalamic nucleus (by 18%), ipsilaterally to the stimulated side. The ventrolateral motor thalamic nucleus as well as the limbic components, posterior cingulate cortex, and anteroventral thalamic nucleus displayed bilateral metabolic activations (by 20-28%). These results indicate that, in addition to its known ipsilateral motor connections, each STH is functionally related to the limbic system bilaterally. It is suggested that the STH is a site where the central motor information is accessible to the limbic system. Quantitative image analysis of individual serial sections in the STH, substantia nigra, and globus pallidus revealed a consistent dorsoventral pattern of topographic interrelations. Stimulation of either the dorsal or the ventral subdivision of the STH induced always stronger activation in the dorsal compartment of the substantia nigra and in the ventral compartment of the globus pallidus. These results suggest that the earlier-described inversion of the dorsoventral functional correspondence between the substantia nigra and globus pallidus may be partly mediated via the subthalamic nerve cells projecting collateral axons to both these areas.


Author Correction: Phylogeny and taxonomic revision of Kernia and Acaulium.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Recognition of parts of famous-face photographs by children: an experimental note.
Children aged between 5 and 10 years were shown photographs of familiar TV personalities, presenters, and celebrities for immediate recognition (naming). The pictures were of whole faces, outer features only (hair, chin, ears), or inner features (eyes, nose, mouth). Only the oldest group (9-10 years) resembled adults in recognising these familiar faces more efficiently from internal than external parts. In the youngest children (5-6 years) there were some indications that the outer face features were more salient, particularly when cartoon characters were included in the array.


miR-485-3p regulated by MALAT1 inhibits osteosarcoma glycolysis and metastasis by directly suppressing c-MET and AKT3/mTOR signalling.
Osteosarcoma (OS) is an extremely malignant bone cancer with high incidence and rapid progression. This study aims to investigate the role and underlying mechanisms of MALAT1 and miR-485-3p in OS. qRT-PCR and Western blotting were utilized to measure the levels of miR-485-3p, MALAT1, c-MET, AKT3, p-mTOR, mTOR, glycolysis-related proteins or migration-related proteins. Colony formation and transwell assay were used to test the roles of miR-485-3p, MALAT1, c-MET and AKT3 in cancer cell proliferation, migration and invasion. Dual luciferase assay was used to validate the interactions of miR-485-3p/c-MET, miR-485-3p/AKT3, and MALAT1/miR-485-3p. Glucose uptake assay and measurement of lactate production were employed to determine the glycolysis process. Mouse tumour xenograft model was used to determine the effect of shMALAT1 and miR-485-3p mimics on tumour growth and metastasis in vivo. miR-485-3p was decreased while c-MET, AKT3, and MALAT1 were increased in human OS tissues and cells. miR-485-3p bound directly to c-MET and AKT3 mRNAs and repressed OS cell glycolysis, proliferation, migration, and invasion through decreasing glycolysis-related proteins and migration-related proteins via inhibiting c-MET and AKT3/mTOR pathway. In addition, MALAT1 interacted with miR-485-3p and disinhibited c-MET and AKT3/mTOR signalling. Knockdown MALAT1 or overexpression of miR-485-3p restrained OS tumour growth and lung metastasis in vivo. miR-485-3p suppresses OS glycolysis, proliferation, and metastasis via inhibiting c-MET and AKT3/mTOR signalling and MALAT1 acts as a sponge of miR-485-3p. MALAT1 and miR-485-3p may be the key regulators in OS progression, and potential molecular targets for future OS therapy.


The members of the Bacillus cereus group are commonly present contaminants of fresh and heat-treated milk.
To determine the level of milk contamination by Bacillus cereus sensu lato, 44 samples were collected from a dairy farm and two independent dairies in northeastern Poland. A total of 680 B. cereus sensu lato isolates were recovered. Based on spore counts, their highest level in milk was found during the spring and summer months. Although significant variations in chromosomal DNA polymorphisms among B. cereus sensu lato isolates were noted based on repetitive element sequence polymorphism (rep-PCR) and pulse-field gel electrophoresis (PFGE), indistinguishable B. cereus isolates were observed in all sampling points and locations. Both B. cereus sensu stricto/Bacillus weihenstephanensis and Bacillus thuringiensis cultured from milk harbored nheA, hblA, and cytK in, respectively, 80%, 55%, and 60% of the isolates. With respect to Bacillus mycoides/Bacillus pseudomycoides, 30% and 70% of theses isolates harbored, respectively, nheA and hblA. The presence of cytK was not detected in any isolate. Our data show the occurrence of potentially toxic B. cereus s.l. in both raw and heat-treated milk, thus emphasizing the requirement for precautions that prevent spore germination and vegetative proliferation by keeping the milk at low temperatures during all steps of production and dispensation to the consumers.


Cost effectiveness of a fluoride varnish daycare program versus usual care in central Winnipeg, Canada.
This project compares the cost effectiveness of a preventive fluoride varnish (FV) program with usual dental care (surgery under general anesthesia [GA]) for preschool children in 2 low-income communities in Winnipeg, Canada. Program impact is described in terms of cost, cavities avoided, and reductions in surgery volume. Aggregate data for 873 children ages 1 to 6 years old enrolled in the Winnipeg Regional Health Authority Daycare Fluoride Varnish Program in January 2018 were analysed using a Markov model. The program was found to save approximately $822.98 per child over 5 years versus usual dental care. There were 4.38 cavities avoided per child and a savings of $187.71/cavity for the FV group. Participants' need for dental surgery under GA was reduced from 19.1% in the usual care group to 1.6% in the FV group (92% reduction) over 5 years. Sensitivity analyses using a Monte Carlo simulation showed that the program was cost effective over usual care 100% of the time. Finally, it was estimated that the program had saved $753,000 since its inception, or approximately $41.15 per FV application. The FV intervention had better health outcomes, lower costs, and was less invasive than usual care involving dental surgery under GA for children enrolled in the program.


Progressive pseudorheumatoid arthritis of childhood (PPAC). A hereditary disorder simulating rheumatoid arthritis.
Five patients are described with a hereditary arthropathy affecting major and minor joints. The main features of this progressive connective tissue disorder are restricted joint mobility, osseous swelling of the interphalangeal and other joints, and platyspondyly. The condition is commonly misdiagnosed as "chronic juvenile polyarthritis with Scheuermann disease". It differs from the rheumatoid-factor-negative polyarticular form of rheumatoid arthritis and other rheumatoid spondylarthropathies by the absence of arthritic and other inflammatory changes, radiographically by the absence of destructive and the presence of dysplastic bone changes. The disorder does not seem to respond to the usual forms of antirheumatoid treatment. Histological studies showed a peculiar, nest-like clustering of chondrocytes in the resting and growth cartilage suggesting that pathogenetically this is a primary disorder of the articular cartilage.


Effects of muscimol, amphetamine, and DAMGO injected into the nucleus accumbens shell on food-reinforced lever pressing by undeprived rats.
Previous studies have shown that large increases in food intake in nondeprived animals can be induced by injections of both the GABA(A) agonist muscimol and the μ-opioid agonist DAMGO into the nucleus accumbens shell (AcbSh), while injections of the catecholamine agonist amphetamine have little effect. In the current study we examined whether injections of these drugs are able to increase food-reinforced lever pressing in nondeprived rats. Twelve subjects were trained to lever press on a continuous reinforcement schedule while food deprived and were then tested after being placed back on ad libitum feeding. Under these conditions, responding was markedly increased by injections of either muscimol or DAMGO, although the onset of the effects of the latter drug was delayed by 30-40 min. In contrast, amphetamine injections failed to increase reinforced lever pressing, although they did enhance responding on a non-reinforced lever, presumably reflecting alterations in behavioral activation. These results demonstrate that stimulation of GABA(A) and μ-opioid receptors within the AcbSh is able to promote not only food intake, but also food-directed operant behavior. In contrast, stimulation of AcbSh dopamine receptors may enhance behavioral arousal, but does not appear to specifically potentiate behaviors directed toward food procurement.


One-step preparation of superhydrophobic acrylonitrile-butadiene-styrene copolymer coating for ultrafast separation of water-in-oil emulsions.
Superhydrophobic membranes with opposite wettability toward water and oil are able to separate water-in-oil emulsions. By constructing porous and hierarchal-structured superhydrophobic coating on filter paper, we hope a quick separation process could be achieved due to the acceleration of both demulsification and penetration process. Here, superhydrophobic coatings were prepared by simply spraying environmental and cost-effective acrylonitrile-butadiene-styrene copolymer (ABS) colloid in dichloromethane onto filter paper. The morphologies and wettability of the obtained coatings were carefully studied. Moreover, the separation performances in dealing with various surfactant-stabilized water-in-oil emulsions (SSWOE) were also investigated to verify our hypothesis. The morphologies of the ABS coatings varied with its weight concentration in dichloromethane and they changed from porous and plain surface into porous and hierarchal-structured surface. Besides, the hydrophobicity of the above coatings varied form hydrophobic to superhydrophobic. Moreover, the resulted superhydrophobic membranes show great separation capability in separating various span 80-stabilized water-in-oil emulsions with oil filtrate purities larger than 99.90% and huge penetration fluxes whose maximum is over 13,000L/(m2h). Thus, we envision that such membrane can be a practical candidate in dealing with water-in-oil emulsions to obtain pure oils.


Capillary electrophoresis determinative and GC-MS confirmatory method for water-soluble organic acids in airborne particulate matter and vehicle emission.
Urban fine airborne particulate matter (PM2.5) and vehicle emission samples were studied for water-soluble low-molecular-weight carboxylic acids using CE with indirect UV detection. Further identification of these acids was achieved using GC-MS as their butyl esters (after derivatization with BF3/butanol). Several dicarboxylic acids in the range C2-C10 including straight-chain, branched-chain, cis- and trans-unsaturated, and aromatic acids were confirmed by GC-MS. In addition, aromatic acids such as benzoate, phthalate, terephthalate, isophthalate, and 4-methylphtalate were present in such samples, but some of these were not well resolved by the used CE method. Oxocarboxylic acids (Cn(w) with n > 4) were also identified by GC-MS but not determined by CE due to lack of standards. The rapidity and simplicity of the CE method were clearly demonstrated, and the method was observed to be advantageous for routine monitoring of water-soluble organic acids in airborne PM2.5 and vehicle emission at low microg/L levels.


Are out-of-school adolescents at higher risk of adverse health outcomes? Evidence from 9 diverse settings in sub-Saharan Africa.
We analysed mutually comparable surveys on adolescent attitudes and behaviours from nine sites in seven sub-Saharan African countries, to determine the relationship between school enrolment and adolescent health outcomes. Data from the Africa Research, Implementation Science, and Education Network cross-sectional adolescent health surveys were used to examine the associations of current school enrolment, self-reported general health and four major adolescent health domains: (i) sexual and reproductive health; (ii) nutrition and non-communicable diseases; (iii) mental health, violence and injury; and (iv) healthcare utilisation. We used multivariable Poisson regression models to calculate relative risk ratios with 95% confidence intervals (CI), controlling for demographic and socio-economic characteristics. We assessed heterogeneity by gender and study site. Across 7829 adolescents aged 10-19, 70.5% were in school at the time of interview. In-school adolescents were 14.3% more likely (95% CI: 6-22) to report that their life is going well; 51.2% less likely (95% CI: 45-67) to report ever having had sexual intercourse; 32.6% more likely (95% CI: 9-61) to report unmet need for health care; and 30.1% less likely (95% CI: 15-43) to report having visited a traditional healer. School enrolment was not significantly associated with malnutrition, low mood, violence or injury. Substantial heterogeneity was identified between genders for sexual and reproductive health, and in-school adolescents were particularly less likely to report adverse health outcomes in settings with high average school enrolment. School enrolment is strongly associated with sexual and reproductive health and healthcare utilisation outcomes across nine sites in sub-Saharan Africa. Keeping adolescents in school may improve key health outcomes, something that can be explored through future longitudinal, mixed-methods, and (quasi-)experimental studies.


Assessment of pain in the neonate.
Accurate pain assessment in preterm and term neonates in the neonatal intensive care unit (NICU) is of vital importance because of the high prevalence of painful experiences in this population, including both daily procedural pain and postoperative pain. Over 40 tools have been developed to assess pain in neonates, and each NICU should choose a limited number of pain assessment tools for different populations and contexts. Only two pain assessment tools have a metric adjustment to account for differences of pain assessment in prematurity. Preterm neonates do not display behavior and physiologic indicators of pain as reliably and specifically as full term infants, and preterm infants are vulnerable to long term sequelae of painful experiences. "Brain-oriented" approaches for more objective measurement of pain in neonates may become available in the future. In the meantime, neonatal pain assessment tools need to be taught, implemented, and their ongoing use optimized to form a consistent, reproducible basis for the safe and effective treatment of neonatal pain.


Proposed injury thresholds for concussion in equestrian sports.
Equestrian helmets are designed to pass certification standards based on linear drop tests onto rigid steel surfaces. However, concussions in equestrian sports occur most commonly when a rider is thrown off a horse and obliquely impacts a compliant surface such as turf or sand. This paper seeks to elucidate the mechanics of such impacts and thereby propose corresponding thresholds for the occurrence of concussion that can improve equestrian helmet standards and designs. The present study examined the biomechanics of real-world equestrian accidents and developed thresholds for the occurrence of concussive injury. Twenty-five concussive and 25 non-concussive falls in equestrian sports were reconstructed using a combination of video analysis, computational and physical reconstruction methods. These represented male and female accidents from horse racing and the cross-country phase of eventing. The resulting thresholds for concussion [59g, 2700rad/s2, 28rad/s, 0.24 (MPS), 6.6kPa and 0.27 (CSMD10) for 50% risk] were consistent with those reported in the literature and represent a unique combination of head kinematic thresholds compared to other sports. Current equestrian helmet standards commonly use a threshold of 250g and a linear drop to a steel anvil resulting in less than 15ms impacts. This investigation found that concussive equestrian accidents occurred from oblique impacts to turf or sand with lower magnitude and longer duration impacts (<130g and >20ms). This suggests that current equestrian helmet standards may not adequately represent real-world concussive impact conditions and, consequently, there is an urgent need to assess the protective capacity of equestrian helmets under real-world conditions.


[Main results of research reported by the Center's Department of Innovation in Radiotherapy].
The efficacy of multimodality conservative treatment for prostate and bladder cancer and cervical carcinoma was improved due to integration of such modem modalities as intra-arterial chemotherapy, local hyperthermia and hyperglycemia and combination of local and systemic radiomodifiers. Our methods use criteria of actual survival and are intended to raise it.


Use of the biotin-streptavidin interaction to improve flavivirus detection by immunofluorescence and ELISA tests.
The specificity and sensitivity of immunofluorescence microscopy and ELISA tests were compared both with and without the use of biotinylated anti-species antibody and streptavidin, conjugated with either fluorescein isothiocyanate or horse radish peroxidase. In the biotin-streptavidin system monoclonal and polyclonal antibodies against yellow fever virus had titres between ten- and fifty-fold higher and background readings, particularly in ELISA tests, were noticeably reduced. Plaque variants of yellow fever virus, selected for their apparent loss of antigenic determinants against some monoclonal antibodies in conventional fluorescence tests, were found to possess the antigenic determinants when tested with the more sensitive system.


High-performance liquid chromatography of amino acids, peptides and proteins. LXXIV. Separation of heparin-binding growth factors by reversed-phase high-performance liquid chromatography.
The separation of several immunologically related forms of the bovine brain basic heparin-binding growth factor by reversed-phase high-performance liquid chromatography is described. With Bakerbond C4 reversed-phase columns, it is possible to resolve the 0.8-1.0 M sodium chloride and the 1.0-1.3 M sodium chloride components from the preceding heparin-Sepharose affinity chromatographic step in the purification procedure for these polypeptide mitogens into multiple active forms, all of which exhibit similar molecular weights and immunoreactivity with specific polyclonal antisera. Structural characterisation suggests that it is likely that these forms represent different stages in the post-translational processing of these polypeptide mitogens.


Effect of the CB1 receptor antagonist, SR141716A, on cannabinoid-induced ocular hypotension in normotensive rabbits.
The present study attempts to indirectly determine if a neuronal cannabinoid (CB1) receptor mediates the intraocular pressure (IOP) reduction effects of arachidonoyl ethanolamide (AEA), its R-alpha-isopropyl analog, and the non-classical cannabinoid, CP-55,940. A series of these cannabinoids were dissolved in an aqueous 10-20% 2-hydroxypropyl-beta-cyclodextrin (2-HP-beta-CD) solution (containing 3% polyvinyl alcohol) and administered (25-62.5 microg) unilaterally to normotensive rabbit eyes. This was repeated on animals pre-treated with a subcutaneous injection (2.5 mg/kg) of the highly specific CB1 receptor antagonist, SR 141716A, dissolved in an aqueous 42% 2-HP-beta-CD solution. AEA, its R-alpha-isopropyl analog, and CP-55,940 reduced IOP upon topical application to a greater degree than was detected in the untreated eye. This reduction was eliminated for the latter two compounds by subcutaneous (s.c.) pretreatment of the rabbits with the CB1 receptor antagonist, but the IOP properties of AEA remained unchanged. SR 141716A administered alone (s.c.), elevated the IOP of both eyes. A CB1 receptor seems involved in the IOP reduction induced by either R-alpha-isopropyl anandamide or CP-55,940. However, AEA apparently functions through a different mechanism.


Experimental portal fibrosis produced by intraportal injection of killed nonpathogenic Escherichia coli in rabbits.
An attempt was made to develop an animal model for the study of the etiology of noncirrhotic portal fibrosis or idiopathic portal hypertension based on the assumption that it is related to chronic abdominal infection. Rabbits were given killed nonpathogenic Escherichia coli intraportally or intravenously. The animals to which a mixture of killed E. coli and rabbit antiserum (aggregated E. coli) was given intraportally developed remarkable histologic changes in the liver. The early inflammatory reactions in the portal area and parenchyma were followed by rapid disappearance of inflammation and development of portal fibrosis with bile duct proliferation. Three intraportal challenges with aggregated E. coli were sufficient to produce pronounced portal fibrosis, although there was considerable variation in response among individual animals. This procedure also produced splenomegaly, and in some animals marked portal hypertension. Injection of nonaggregated killed E. coli into the portal vein or aggregated E. coli into the ear vein also caused similar hepatic changes, but they were milder in degree. These histologic changes resemble portal fibrosis seen in idiopathic portal hypertension and, less closely, pericholangitis associated with inflammatory bowel disease in humans.


Green factors stimulating the purchase intention of innovative luxury organic beauty products: Implications for sustainable development.
Orienting consumers toward organic eco-friendly beauty products is a societal challenge that resonates with growing environmental concerns following COP 21, when entrepreneurs in the cosmetic industry initiated ambitious plans to increase the proportion of natural components in their products. This study examines how green factors impact customers' intention to purchase premium organic beauty products. We explore the mediating roles of trust and attitude on this purchase intention, using the SOR paradigm and the dual factor theory, an original approach. Data was collected from 398 respondents using convenience sampling and analysed using the IBM SPSS 22 version and AMOS 22 version package applying structural equation modelling. We show that the mediating role of trust and attitude is of the utmost importance to ensure a sustainable orientation of customers toward organic products. The findings suggest (a) green ads, green brand image and perceived consumer effectiveness positively influence consumers' attitude toward luxury organic beauty products; (b) LOHAS consumption tendency does not impact consumers' attitudes; (c) trust has a significantly negative impact on the consumer's attitude; and (d) likewise, consumers' attitude mediate the intention to purchase luxury organic beauty products. The research has significant implications for understanding India's premium organic beauty goods market and for companies to develop new strategies to market their organic cosmetics. The study also encourages policymakers to provide necessary subsidies to new organic beauty entrepreneurs.


Running has differential effects on NPY, opiates, and cell proliferation in an animal model of depression and controls.
Physical activity has documented beneficial effect in treatment of depression. Recently, we found an antidepressant-like effect of running in an animal model of depression, the Flinders Sensitive Line (FSL) and demonstrated that it was associated with increased hippocampal cell proliferation. In this study, we analyzed levels of mRNAs encoding the neuropeptide Y (NPY) and the opioid peptides dynorphin and enkephalin in hippocampus and correlated these to cell proliferation in the FSL and in the 'nondepressed' Flinders Resistant Line (FRL) strain, with/without access to running wheels. Running increased NPY mRNA in dentate gyrus and the CA4 region in FSL, but not in FRL rats. NPY mRNA increase was correlated to increased cell proliferation in the subgranular zone of dentate gyrus. Baseline dynorphin and enkephalin mRNA levels in the dentate gyrus were lower in the FSL compared to the FRL strain. Running had no effect on dynorphin and enkephalin mRNAs in the FSL strain but it decreased dynorphin mRNA, and there was a trend to increased enkephalin mRNA in the FRL rats. Thus, it would appear that the CNS effects of running are different in 'depressed' and control animals; modification of NPY, a peptide associated with depression and anxiety, in depressed animals, vs effects on opioids, associated with the reward systems, in healthy controls. Our data support the hypothesis that NPY neurotransmission in hippocampus is malfunctioning in depression and that antidepressive treatment, in this case wheel running, will normalize it. In addition, we also show that the increased NPY after running is correlated to increased cell proliferation, which is associated with an antidepressive-like effect.


[Bisphosphonate and denosumab-related osteonecrosis of the jaw: Epidemiology, diagnosis and management].
Bisphosphonate-related osteonecrosis of the jaw have been widely described. Denosumab has recently been associated to ONJ. Guidance to clinicians is based on criteria established by the American Association of Oral and Maxillofacial Surgeons (AAOMS). Treatment should be multidisciplinary. Two options are available and have to be discussed on the basis of associated therapeutic, patient's general state of health and possibility of therapeutic window during cancer treatment: conservative (medication and conservative surgery like superficial debridement) and extensive surgery. Therefore, we report an update about management strategies of osteonecrosis of the jaw and two cases of patients with a stage 2 osteonecrosis of the jaw only treated with mouth rinses, antibiotics and debridement and complete healing.


[Consultation for patients with cheilognathopalatoschisis and their family members. Cooperation between orthodontists and human geneticists].
In children with a cleft lip and palate the question of aetiology always arises. This is the case in particular when the neonatologist discovers or suspects additional malformations. Since newborn children with cleft lip and palate are now usually brought for initial treatment to an orthodontist, it is his responsibility to inform the parents about the possibility and necessity of genetic counselling and possibly, to initiate contact with the appropriate institute. This is always the case when the wish for further children is expressed. If the orthodontist recognizes microsymptoms in the parents or finds indications of their occurrence in the family, he will strongly recommend such a consultation, with cleft lip and palate patients, the orthodontist should discuss a genetic consultation as part of his confidential relationship with the patient so that the young patients understand the possible risk for the next generation. This consultation can bring enormous psychological relief for the patient if there is only a slight risk of recurrence.


Sensory, chemical and bacteriological changes during storage of iced squid (Todaropsis eblanae).
To relate sensory shelf-life of iced whole and gutted squid to bacterial growth and chemical changes. Cooked mantles from whole and gutted individuals were rejected after 10 and 12 days of storage, respectively, due to ammoniacal off-odours. Rate of production of both ammonia and trimethylamine was highest in the whole lot. Agmatine, which was only present in trace amounts in freshly-caught squid, increased rapidly in both lots. The main microflora at the time of sensory rejection of iced whole squid included Gram-negative, motile and non-fermentative rods, which were psychrophilic and had a requirement for NaCl. 16S rDNA sequence analyses identified the strains as belonging to the genus Pseudoalteromonas. Shewanella putrefaciens, Pseudoalteromonas sp. and Pseudomonas sp. dominated in spoiled gutted squid. Identification of strains from the stomach and digestive gland of recently-captured squid showed that the main flora consisted of Photobacterium phosphoreum. Spoilage of iced squid is likely to result from a combination of autolytic and bacterial changes. Agmatine seems to be an excellent freshness indicator. Photobacterium phosphoreum may contribute to spoilage through activity in the digestive gland, followed by diffusion of volatile compounds and amines to the mantle. Due to the psychrophilic nature of P. phosphoreum and Pseudoalteromonas sp., spread-plating and low temperature incubation are recommended for bacteriological evaluation of iced squid.


A Two-Dimensional Metal-Organic Polymer Enabled by Robust Nickel-Nitrogen and Hydrogen Bonds for Exceptional Sodium-Ion Storage.
Organic electrode materials suffer from low electronic conductivity and poor structure stability. Herein, a metal-organic polymer, Ni-coordinated tetramino-benzoquinone (Ni-TABQ), is synthesized via d-π hybridization. The polymer chains are stitched by hydrogen bonds to feature as a robust two-dimensional (2D) layered structure. It offers both electron conduction and Na+ diffusion pathways along the directions of the polymer chains and the hydrogen bonds. With both the conjugated benzoid carbonyls and imines as the redox centers for the insertion and extraction of Na+ , the Ni-TABQ delivers high capacities of about 469.5 mAh g-1 at 100 mA g-1 and 345.4 mAh g-1 at 8 A g-1 . The large capacities are sustained for 100 cycles with almost 100 % coulombic efficiencies. The exceptional electrochemical performance is attributed to the unique 2D electron conduction and Na+ diffusion pathways enabled by the robust Ni-N and hydrogen bonds.


A label-free kissing complexes-induced fluorescence aptasensor using DNA-templated silver nanoclusters as a signal transducer.
Riboswitches are complex folded RNA domains that serve as receptors for specific metabolites which identified in prokaryotes. They are comprised of a biosensor that includes the binding site for a small ligand and they respond to association with this ligand by undergoing a conformational change. In the present study, we report on the integration of silver nanoclusters (AgNCs) and riboswitches for the development of a kissing complexes-induced aptasensor (KCIA). We specifically apply the tunable riboswitches properties of this strategy to demonstrate the multiplexes analysis of adenosine and adenosine deaminase (ADA). This strategy allows for simple tethering of the specific oligonucleotides stabilizing the AgNCs to the nucleic acid probes. This is a new concept for aptasensors, and opens an opportunity for design of more novel biosensors based on the kissing complexes-induced strategy.


Cost assessment of the production of pyrrolizidine alkaloids in ragwort (Senecio jacobaea L.).
Costs of pyrrolizidine alkaloid (Pa) production in vegetative ragwort (Senecio jacobaea) were examined under conditions in which plant growth was limited by light, nitrogen and phosphorus. Measurable costs of Pa production were demonstrated under light-limiting conditions. Plants with higher Pa concentrations grew more slowly than those with lower Pa concentration. Under nitrogen- and phosphorus-limited conditions no trade-off between Pa production and growth was observed.


Identification, synthesis and evaluation of substituted benzofurazans as inhibitors of CREB-mediated gene transcription.
Cyclic-AMP response-element binding protein (CREB) is a stimulus-activated transcription factor. Its transcription activity requires its binding with CREB-binding protein (CBP) after CREB is phosphorylated at Ser133. The domains involved for CREB-CBP interaction are kinase-inducible domain (KID) from CREB and KID-interacting domain (KIX) from CBP. Recent studies suggest that CREB is an attractive target for novel cancer therapeutics. To identify novel chemotypes as inhibitors of KIX-KID interaction, we screened the NCI-diversity set of compounds using a split renilla luciferase assay and identified 2-[(7-nitrobenzo[c][1,2,5]oxadiazol-4-yl)thio]pyridine 1-oxide (compound 1, NSC228155) as a potent inhibitor of KIX-KID interaction. However, compound 1 was not particularly selective against CREB-mediated gene transcription in living HEK 293T cells. Further structure-activityrelationship studies identified 4-aniline substituted nitrobenzofurazans with improved selectivity.


The effect of 24-hour sleep deprivation on subjective time perception.
In this study, we investigated the effect of 24-h total sleep deprivation on subjective time perception. Twenty-five participants aged 18-35 years (13 female and 12 male) were recruited. Time perception and cognitive assessments were performed twice: after a regular night's sleep and following a 24-h sleep deprivation. The retrospective and prospective tasks were used to measure time perception. In order to prevent order effect, the test orders were randomized. The Stroop test and the Wechsler Memory Scale-III were used to evaluate attention, processing speed, and memory. The repeated measures ANOVA was used to examine gender-by-sleep deprivation interactions on time perception. We found that retrospective time perception was significantly prolonged after sleep deprivation (p < 0.05). Women had a shorter prospective time estimation rate after adequate sleep than men, but this difference disappeared after sleep deprivation. The Stroop test showed improvement in cognitive flexibility after sleep deprivation (p < 0.05), and short-term or working memory appeared unaffected by one night of sleep deprivation. There was a negative correlation between sleepiness rate and working memory function in female subgroup. The results suggest that even short-term sleep deprivation can significantly affect time perception, which may have important implications in critical situations.


[Effect of maximum dose of atorvastatin on inflammation, thrombogenesis and fibrinolysis in high-risk patients with ischemic heart disease].
It has been suggested that high doses of statins can be more effective in reducing the incidence of new cardiovascular events than conventional doses. The present study analyzed the effect of increasing the atorvastatin dose to 80 mg/day on indices of inflammation (C-reactive protein or CRP), thrombogenesis (prothrombin fragment [F1+2]) and fibrinolysis (tissue-type plasminogen activator antigen, t-PA, and its inhibitor PAI-1) in high-risk patients with ischemic heart disease. We studied 27 patients with high-risk coronary heart disease who had lipid levels above those recommended despite treatment with atorvastatin at 40 mg/day. At baseline, patients were compared with 21 normocholesterolemic subjects without arteriosclerotic disease. Twenty-four patients were reevaluated 3 months after the atorvastatin dose was increased to 80 mg/day. The CRP, F1+2, t-PA and PAI-1 levels were significantly higher in patients than control subjects (all P<.05). After the atorvastatin dose was increased, significant reductions in CRP, F1+2, and PAI-1 levels were observed (P<.05). There was a significant positive correlation between the reduction in cholesterol level and that in F1+2 (r=0.43; P=.023). No other significant correlations were found. In a group of patient with high-risk heart disease and elevated lipid levels, increasing the atorvastatin dose led to significant improvements in inflammatory, thrombogenic, and hypofibrinolytic states.


Should parents be present during emergency department procedures on children, and who should make that decision? A survey of emergency physician and nurse attitudes.
To survey physician and nurse attitudes regarding parental presence during painful procedures on children performed in the emergency department (ED) and who should make that decision. The design was an anonymous written survey consisting of six clinical scenarios distributed to all staff and resident physicians and nurses in ten EDs at institutions in the United States routinely caring for children. Participants were asked whether parents should remain with children undergoing intravenous (IV) placement, laceration repair, lumbar puncture, conscious sedation, major resuscitation, and major resuscitation with death. They also were asked who should make the decision. The percentage of physicians who responded that parents should be present was 91.3% for peripheral IV start, 93.3% for laceration repair, 65.7% for lumbar puncture, 83.1% for conscious sedation, 31.9% for major resuscitation, and 35.6% for major resuscitation where death was likely. The percentage of nurses who responded that parents should be present was 86.8% for peripheral IV start, 89.6% for laceration repair, 55.0% for lumbar puncture, 74.9% for conscious sedation, 41.4% for major resuscitation, and 54.3% for major resuscitation where death was likely. In 64.8% of the completed surveys, the physicians indicated that they alone or in conjunction with a parent should make the decision. In 61.5% of the completed surveys, the nurses indicated that they should be involved in the decision. A majority of emergency physicians and nurses indicated parents should be present for some invasive pediatric procedures. However, as the invasiveness of the pediatric procedures increased, fewer physicians and nurses believed that parents should be present.


Hepatitis C Genotype 3 Infection: Pathogenesis and Treatment Horizons.
Genotype 3 hepatitis C infection is the second most common genotype worldwide and accounts for most infections in Southeast Asia. It is a particularly ominous genotype because it has been linked to increased mortality, specifically increased late-stage liver events, accelerated development of hepatic fibrosis, and an increased risk of hepatocellular carcinoma. As new treatment regimens for hepatitis C have been emerging, treatment of genotype 3 often requires longer treatment duration with decreased response rates as compared with other genotypes.


Electrophysiological, histochemical, and hormonal adaptation of rat muscle after prolonged hindlimb suspension.
The perspective of long-duration flights for future exploration, imply more research in the field of human adaptation. Previous studies in rat muscles hindlimb suspension (HLS), indicated muscle atrophy and a change of fibre composition from slow-to-fast twitch types. However, the contractile responses to long-term unloading is still unclear. Fifteen adult Wistar rats were studied in 45 and 70 days of muscle unweighting and soleus (SOL) muscle as well as extensor digitorum longus (EDL) were prepared for electrophysiological recordings (single, twitch, tetanic contraction and fatigue) and histochemical stainings. The loss of muscle mass observed was greater in the soleus muscle. The analysis of electrophysiological properties of both EDL and SOL showed significant main effects of group, of number of unweighting days and fatigue properties. Single contraction for soleus muscle remained unchanged but there was statistically significant difference for tetanic contraction and fatigue. Fatigue index showed a decrease for the control rats, but increase for the HLS rats. According to the histochemical findings there was a shift from oxidative to glycolytic metabolism during HLS. The data suggested that muscles atrophied, but they presented an adaptation pattern, while their endurance in fatigue was decreased.


Immunoglobulin E response to pertussis toxin in whooping cough and after immunization with a whole-cell and an acellular pertussis vaccine.
Immunoglobulin E antibodies to pertussis toxin (PT-IgE) were demonstrated in 15 of 23 (65%) patients with culture-confirmed pertussis. In 6 individuals there was a low-grade PT-IgE response after 6-9 weeks of disease and in 9 a rapid PT-IgE response, appearing 1-3 weeks after onset of symptoms. The PT-IgE antibody levels in immunized individuals were higher than in the non immunized. Following primary immunization of 23 children with a monovalent whole-cell pertussis vaccine (Burroughs-Wellcome, UK) or with an acellular pertussis vaccine (JNIH-6, Biken, Japan) a late low-grade PT-IgE response was found in 8 (35%). In 7/10 children previously immunized with the JNIH-6, a booster injection 16 months later with the same vaccine resulted in a rapidly appearing PT-IgE antibody response. In contrast, none of 13 children initially immunized with the monovalent whole-cell vaccine and then boostered with either this vaccine or JNIH-6 had detectable PT-IgE antibodies after the booster injection. The study shows that IgE-antibodies to pertussis toxin commonly appear in patients with whooping cough and that the kinetics and the magnitude of the response is influenced by previous exposure to the antigen. A PT-IgE response may also follow pertussis immunization.


Converting catabolic ornithine carbamoyltransferase to an anabolic enzyme.
Pseudomonas aeruginosa has an anabolic and a catabolic ornithine carbamoyltransferase (OTCase). In vitro, these homologous enzymes catalyze the same reaction (ornithine + carbamoyl phosphate (CP) in equilibrium citrulline + Pi), yet in vivo they function unidirectionally owing to specific kinetic properties. The catabolic OTC-ase cannot promote the anabolic reaction (citrulline formation) in vivo because of a sigmoidal CP saturation curve and a high CP concentration for half-maximal velocity. The structural basis for this kinetic specialization was examined. The catabolic OTCase lost most of its homotropic cooperativity and gained anabolic activity when an amino acid residue near the CP binding site, Glu-106, was replaced by alanine or glycine. In the anabolic OTCase of Escherichia coli the glutamine residue corresponding to Glu-106 was exchanged for glutamate; however, in this case no CP cooperativity was acquired. Thus, in catabolic OTCase, sequence features in addition to Glu-106 are important for sigmoidal CP saturation, and such a sequence was identified in the C-terminal part. By an in vivo gene fusion technique the 9 C-terminal amino acids of catabolic OTCase were replaced by the homologous 8 amino acids from anabolic OTCase of E. coli; the hybrid enzyme had a markedly reduced homotropic cooperativity. This gene fusion method should be generally useful for directed enzyme evolution.


Neuromuscular response to varying pressures created by tightness of restriction cuff.
Variation in regional body composition between genders may change the degree of pressure created by the tightness of cuff used during blood flow restriction training resulting in changes in the level of neuromuscular activation. This study investigates the effects of tightness of cuff and skin and subcutaneous fat thickness on electromyography (EMG) amplitude (RMS) and median frequency (MDF) during exercises and strength testing. Subjects performed knee-extension exercises with varying tightness of cuff while using EMG to measure changes in neuromuscular response. EMG RMS was significantly affected by tightness of cuff and skin and subcutaneous fat thickness. The strongest individual variable for the changes in MDF was also skin and subcutaneous-fat thickness. The changes in EMG response due to tightness of cuff and the effect of skin and subcutaneous fat thickness on tightness of cuff prove the importance of details on BFR protocol and leg composition on neuromuscular function during BFR exercises.


Vapor-phase biodegradation and natural attenuation of petroleum VOCs in the unsaturated zone: A microcosm study.
Traditional natural attenuation studies focus on aqueous process in the saturated zone while vapor-phase biodegradation and natural attenuation in the unsaturated zone received much less attention. This study used microcosm experiments to explore the vapor-phase biodegradation and natural attenuation of 23 petroleum VOCs in the unsaturated zone including 7 monoaromatic hydrocarbons, 6 n-alkanes, 4 cycloalkanes, 3 alkylcycloalkanes and 3 fuel ethers. We found that monoaromatic hydrocarbon vapors were easily attenuated with significantly high first-order attenuation rates (9.48 d-1-43.20 d-1) in live yellow earth, of which toluene and benzene had the highest rates (43.20 d-1 and 28.32 d-1, respectively). The 13 aliphatic hydrocarbons and 3 fuel ethers all have relatively low attenuation rates (<0.54 d-1) in live soil and negligible biodegradation contribution. We explored the effects of soil types (black soil, yellow earth, lateritic red earth and quartz sand), soil moisture (2, 5, 10, and 17 wt%) contents and temperatures (4, 15, 25, 35 and 45 °C) on the vapor attenuation. Results showed that increasing soil organic matter (SOM) content, silt content, porosity and soil microorganism numbers enhanced contaminant attenuation and remediation efficiency. Increasing moisture content reduced the apparent first-order biodegradation rates of monoaromatic hydrocarbon vapors. The vapor-phase biodegradation had optimal temperature (∼25 °C in yellow earth) and increasing or decreasing temperature slowed down biodegradation rate. Overall, this study enhanced our understanding of vapor-phase biodegradation and natural attenuation of petroleum VOCs in the unsaturated zone, which is critical for the long-term management and remediation of petroleum contaminated site.


Multiple Skin Abscesses Caused by Rhizopus sp. Infection after Candida albicans Infection in an Immunocompromised Patient.
A 66-year-old woman with diabetes who was treated with prednisolone (15 mg/day) for autoimmune hepatitis developed multiple erythematous nodules with retention of purulent fluid on her lower right limb. Candida albicans was cultured from the nodules. She was started on oral fluconazole, and the lesions subsided. However, multiple dark-red abscesses and indurations newly appeared on the left crus. Histopathological examination showed numerous branched hyphae, and tissue culture yielded a Rhizopus microsporus-related fungus. She was treated with liposomal amphotericin B combined with drainage and debridement. However, she died because of poor control of the infection and hepatic disorder.


Simultaneous determination of JTT-501 and its main metabolite in human plasma by liquid chromatography-ionspray mass spectrometry.
An LC-MS-MS analytical method was developed for the determination of a new antidiabetic agent, JTT-501 and its main metabolite (JTP-20604) in human plasma. The compounds were isolated from plasma by protein precipitation before analysis by HPLC with atmospheric pressure positive ionisation MS-MS detection. An isotopically labelled analog of JTT-501 was used as the internal standard. Linearity was demonstrated over the calibration range of about 5-10000 ng/ml for both compounds. The assay was validated with respect to accuracy, precision and analyte stability. This method was used for the determination of plasma concentrations for the two compounds in a clinical tolerability study. A cross-validation exercise between two different mass spectrometers, used for the determination of clinical samples, is also reported.


[Dead-channel-like part of thoracic esophagus: cut-off sign in the upper gastrointestinal tract].
The colon cutoff sign had been published four decades ago. In this retrospective study a new localisation of syndrome seen on plain film esophagography. The syndrome is formal in 32 cases (2.23%) of 1430 patients is described. Touched persons are 76 +/- 9 years old. The arched inflexion of supradiaphragmatic esophagus related to stage of osteoporosis and incidence of vertebral body fractures besides height of thoracic cavity and kyphosis. Its convexity to abnormality of phrenicoesophageal membrane and hiatus is attributed. The deformity of esophagus occurs 3.75 seven times more often in female than in male patients. Not provable esophageal autopathies.


The In Vitro Invasion Inhibition Assay (IIA) for Plasmodium vivax.
Plasmodium vivax is considered as the most widely distributed human malaria parasite outside Africa. Studies of P. vivax malaria have always been limited due to the lack of continuously in vitro-propagated parasite lines. Due to this limitation, studies on P. vivax have lagged behind that of P. falciparum, which is routinely maintained in in vitro blood-stage culture. This method allows for the short-term ex vivo culture of P. vivax blood stages and as such offers a wealth of opportunities to study the biology of the blood stages of the parasite. In this chapter we describe the in vitro erythrocyte invasion inhibition assay (IIA) for P. vivax, which can be used as a powerful tool for blood-stage vaccine screening. The major challenges of this assay are the purification of schizont-stage parasites and host reticulocytes. The purification methods for both P. vivax schizont-stage parasites and reticulocytes as detailed here have been developed and simplified. The protocols in this chapter have been optimized to ensure that IIA becomes a more feasible and reliable assay.


Gastrointestinal dysbiosis following diethylhexyl phthalate exposure in zebrafish (Danio rerio): Altered microbial diversity, functionality, and network connectivity.
Microbiome community structure is intimately involved in key biological functions in the gastrointestinal (GI) system including nutrient absorption and lipid metabolism. Recent evidence suggests that disruption of the GI microbiome is a contributing factor to metabolic disorders and obesity. Poor diet and chemical exposure have been independently shown to cause disruption of the GI microbiome community structure and function. We hypothesized that the addition a chemical exposure to overfeeding exacerbates adverse effects on the GI microbiome community structure and function. To test this hypothesis, adult zebrafish were fed a normal feeding regime (Control), an overfeeding regime (OF), or an overfeeding regime contaminated with diethylhexyl phthalate (OF + DEHP), a suspected obesogen-inducing chemical. After 60 days, fecal matter was collected for sequencing, identification, and quantification of the GI microbiome using the 16s rRNA hypervariable region. Analysis of beta diversity indicated distinct microbial profiles between treatments with the largest divergence between Control and OF + DEHP groups. Based upon functional predictions, OF + DEHP treatment altered carbohydrate metabolism, while both OF and OF + DEHP affected biosynthesis of fatty acids and lipid metabolism. Co-occurrence network analysis revealed decreases in cluster size and a fracturing of the microbial community network into unconnected components and a loss of keystone species in the OF + DEHP treatment when compared to Control and OF treatments. Data suggest that the addition of DEHP in the diet may exacerbate microbial dysbiosis, a consequence that may explain in part its role as an obesogenic chemical.


Neurotensin: contractile activity, specific binding, and lack of effect on cyclic nucleotides in intestinal smooth muscle.
Nuerotensin contracted the isolated longitudinal smooth muscle strip of the guinea-pig intestine. It induced a biphasic response (relaxation followed by contraction) when the muscle was contracted by histamine. Tetrodotoxin blocked the contraction and the contraction phase of the biphasic response. Dose responses of the relaxing effect of neurotensin and its analogs D-Arg8-neurotensin and D-Arg 9-neurotensin on tetrodotoxin-treated muscle gave EC50 values of 5 nM, 5.5 nM and 110 nM for the three peptides, respectively. [3H]Neurotensin bound specifically to membranes prepared from isolated longitudinal muscle strips of the guinea-pig intestine. In binding studies using [3H]neurotensin and unlabelled peptides, the KDs of neurotensin, D-Arg 8-neurotensin and D-Arg9 neurotensin were 4 nM, 2 nM and 300 nM, respectively, values which are in close agreement with the EC50 of the three peptides. Neurotensin had no effect on the cAMP and cGMP contents in longitudinal intestinal muscle strips of the guinea pig, an observation which suggests that cyclic nucleotides are not involved in the mechanism of action of neurotensin in this muscle preparation.


Differential prepuberal handling modifies behaviour and excitatory amino acids in the forebrain of the Naples High-Excitability rats.
Naples High-Excitability (NHE) rats model the mesocortical variant of Attention-Deficit Hyperactivity Disorder (ADHD). Recently, a high level of excitatory amino acids (EAA) has been found in the forebrain of NHE rats. The aim of this study was to verify the effect of postnatal stimulation in prepuberal rats on forebrain EAA. Thus, prepuberal NHE and Naples Random Bred (NRB) control rats were daily handled (PS) or they were left undisturbed throughout (NO-PS). One hour after the last stimulation, PS and NO-PS rats were exposed to a spatial novelty in a Làt-maze and one day later to a non-reinforced Olton maze. In both tests the horizontal (HA) and vertical (frequency - VA and duration of rearing - RD) components of behaviour indexed activity and non-selective attention (NSA). Moreover, in the Olton maze the position of the number of arms visited before first repetition (FE) and to criterion (NVTC), indexed selective spatial attention (SSA). Amino acids were detected by HPLC in prefrontal cortex (PFC), striatum (STR), hippocampus (HPC) and hypothalamus (HYP). Results indicate that (i) in the Làt-maze, only for HA, NO-PS NHE rats were more active than PS, (ii) in the Olton maze NO-PS rats of both lines showed shorter rearing durations than PS, (iii) EAA level was higher in NHE than in NRB rats and (iv) NO-PS vs. PS treatment increased level of EAA across the forebrain in both rat lines. In contrast in NHE NO-PS rats L-glutamate (L-Glu) decreased in HYP and L-aspartate (L-Asp) decreased in HPC. In conclusion, postnatal stimulation in prepuberal rats significantly affects forebrain excitatory amino acids and behaviour in NHE line. Thus EAA are modulated by genetic determinants and environmental (epigenetic) factors.


The thymus gland: a target organ for growth hormone.
Increasing evidence has placed hormones and neuropeptides among potent immunomodulators, in both health and disease. Herein, we focus on the effects of growth hormone (GH) upon the thymus. Exogenous GH enhances thymic microenvironmental cell-derived secretory products such as cytokines and thymic hormones. Moreover, GH increases thymic epithelial cell (TEC) proliferation in vitro, and exhibits a synergistic effect with anti-CD3 in stimulating thymocyte proliferation, which is in keeping with the data showing that transgenic mice overexpressing GH or GH-releasing hormone exhibit overgrowth of the thymus. GH also influences thymocyte traffic: it increases human T-cell progenitor engraftment into the thymus; augments TEC/thymocyte adhesion and the traffic of thymocytes in the lymphoepithelial complexes, the thymic nurse cells; modulates in vivo the homing of recent thymic emigrants, enhancing the numbers of fluroscein isothiocyanate (FITC)+ cells in the lymph nodes and diminishing them in the spleen. In keeping with the effects of GH upon thymic cells is the detection of GH receptors in both TEC and thymocytes. Additionally, data indicate that insulin-like growth factor (IGF)-1 is involved in several effects of GH in the thymus, including the modulation of thymulin secretion, TEC proliferation as well as thymocyte/TEC adhesion. This is in keeping with the demonstration of IGF-1 production and expression of IGF-1 by TEC and thymocytes. Also, it should be envisioned as an intrathymic circuitry, involving not only IGF-1, but also GH itself, as intrathymic GH expression is seen both in TEC and in thymocytes, and that thymocyte-derived GH could enhance thymocyte proliferation. Finally, the possibility that GH improve thymic functions, including thymocyte proliferation and migration, places this molecule as a potential therapeutic adjuvant in immunodeficiency conditions associated with thymocyte decrease and loss of peripheral T cells.


Temperament and parenting predicting anxiety change in cognitive behavioral therapy: the role of mothers, fathers, and children.
A considerable amount of children with anxiety disorders do not benefit sufficiently from cognitive behavioral treatment. The present study examines the predictive role of child temperament, parent temperament and parenting style in the context of treatment outcome. Participants were 145 children and adolescents (ages 8-18) with DSM-IV-TR anxiety disorders who received a 12-session CBT program and were assessed at pretreatment, posttreatment and three months follow-up. Multiple-regression analyses were used to evaluate the following pretreatment and posttreatment variables as potential predictors of treatment response at follow-up: baseline level of anxiety symptoms, child reported maternal and paternal rearing style (emotional warmth, rejection, and overprotection), parent reported child temperament traits (negative affect, effortful control, and extraversion), and mothers' and fathers' self-report temperament traits. More maternal negative affect and less emotional warmth as perceived by the child before treatment were related to less favorable treatment outcome (accounting for 29% of the variance in anxiety at follow-up). Furthermore, maternal negative affect and children's extraversion measured after treatment also predicted anxiety at follow-up (together accounting for 19% of the variance). Paternal temperament and parenting style were unrelated to treatment outcome, as were children's pretreatment temperament traits. The results suggest that tailoring intervention to include strategies to reduce maternal negative affect and promote an emotional warm rearing style may improve treatment outcome.


From Ampesie to French fries: systematising the characteristics, drivers and impacts of diet change in rapidly urbanising Accra.
Sub-Saharan Africa (SSA) is urbanising rapidly. One of the most visible outcomes of this urbanisation process is the change in the diets of urban residents. However, diet change in the context of rapid urbanisation is a complex and multi-dimensional phenomenon that encompasses multiple intersecting historical, environmental, socioeconomic, and political aspects. This study aims to unravel and systematise the characteristics, drivers and impacts of diet changes in Accra, through the interviews of multiple stakeholders and Causal Loop Diagrams. Diet change is characterised by the increased consumption of certain foodstuff such as rice, chicken, fish, vegetable oil, sugar, and ultra-processed food (UPF), and the decreased consumption of traditional foodstuff such as roots, tubers, and some cereals such as millet. These changes are driven by multiple factors, including among others, changes in income, sociocultural practices, energy access, and policy and trade regimes, as well as the proliferation of supermarkets and food vendors. Collectively, these diet changes have a series of environmental, socioeconomic, and health/nutrition-related impacts. Our results highlight the need to understand in a comprehensive manner the complex processes shaping diet change in the context of urbanisation, as a means of identifying effective interventions to promote healthy and sustainable urban diets in SSA. The development of such intervention should embrace a multi-stakeholder perspective, considering that the relevant urban actors have radically different perspectives and interests at this interface of urbanisation and diet change. The online version contains supplementary material available at 10.1007/s11625-022-01195-y.


Valuing Sets of Potential Transplants in a Kidney Paired Donation Network.
In kidney paired donation (KPD), incompatible donor-candidate pairs and non-directed (also known as altruistic) donors are pooled together with the aim of maximizing the total utility of transplants realized via donor exchanges. We consider a setting in which disjoint sets of potential transplants are selected at regular intervals, with fallback options available within each proposed set in the case of individual donor, candidate or match failure. We develop methods for calculating the expected utility for such sets under a realistic probability model for the KPD. Exact expected utility calculations for these sets are compared to estimates based on Monte Carlo samples of the underlying network. Models and methods are extended to include transplant candidates who join KPD with more than one incompatible donor. Microsimulations demonstrate the superiority of accounting for failure probability and fallback options, as well as candidates joining with additional donors, in terms of realized transplants and waiting time for candidates.


Does simile comprehension differ from metaphor comprehension? A functional MRI study.
Since Aristotle, people have believed that metaphors and similes express the same type of figurative meaning, despite the fact that they are expressed with different sentence patterns. In contrast, recent psycholinguistic models have suggested that metaphors and similes may promote different comprehension processes. In this study, we investigated the neural substrates involved in the comprehension of metaphor and simile using functional magnetic resonance imaging (fMRI) to evaluate whether simile comprehension differs from metaphor comprehension or not. In the metaphor and simile sentence conditions, higher activation was seen in the left inferior frontal gyrus. This result suggests that the activation in both metaphor and simile conditions indicates similar patterns in the left frontal region. The results also suggest that similes elicit higher levels of activation in the medial frontal region which might be related to inference processes, whereas metaphors elicit more right-sided prefrontal activation which might be related to figurative language comprehension.


Sacral neuromodulation: sacral anatomy and optimal lead placement.
To develop an instructional video that correlates cadaveric anatomy with fluoroscopic images to assist in conceptualization of optimal placement of the foramen needle and lead to complete an efficient and successful sacral neuromodulation (SNM) procedure. A SNM procedure was performed and recorded on a fresh female cadaver. Fluoroscopic images were obtained during the procedure to highlight the bony relationships to the S3 foramen and nerve. Dissection of the anterior and posterior sacrum was completed to highlight the tract of the S3 nerve. Techniques to increase the likelihood of optimal foramen needle and thus lead placement were highlighted. This video demonstrates how achieving optimal foramen needle placement within the S3 foramen is key to optimal lead placement. Understanding the relationship of the bony landmarks on fluoroscopy to the S3 nerve and foramen, seen in the cadaveric dissections, are important in understanding how to achieve optimal lead placement. This optimization should lead to decreased operating room time, maximization of programming options, and decreased amplitude requirements.


Voglibose potentiates the hepatotoxicity of carbon tetrachloride and acetaminophen by inducing CYP2E1 in rats.
: Voglibose is an alpha-glucosidase inhibitor used to decrease postprandial hyperglycemia in diabetic patients. Although clinical concern has not yet been raised, hepatic dysfunction has been reported in a few patients taking this drug. : In the present study, we studied the effects of voglibose on the hepatotoxicity of carbon tetrachloride (CCl(4)) and acetaminophen (APAP) in rats, since both of these agents exert their effects through isoforms of cytochrome P450. Male Sprague-Dawley rats were given a daily ration (20g) of powdered chow diet containing 0, 2.5, 5.0 or 10.0mg/100g of voglibose. Three weeks later, the rats were challenged with either 0.50g/kg CCl(4) orally or 0.75g/kg APAP intraperitoneally for biochemical examinations or killed for an in vivo metabolism study. : Voglibose at these three experimental doses potentiated CCl(4) and APAP hepatotoxicity, as evidenced by significantly increased levels of both plasma asparate transaminase (AST) and alanine transaminae (ALT). The glutathione (GSH) content was decreased while malondialdehyde (MDA) increased in the liver after CCl(4) or APAP administration. Hepatic cytochrome P450 2E1 (CYP2E1) concentration was increased at doses of 5.0 and 10.0mg/100g of voglibose and its activity increased in the three voglibose dosage groups, while hepatic cytochrome P450 3A (CYP3A) and cytochrome P450 1A2 (CYP1A2) were only slightly changed at any dose. : Our study demonstrated that voglibose can potentiate CCl(4) and APAP hepatotoxicity in rats by inducing hepatic CYP2E1.


Electrical Stimulation Able to Trigger Locomotor Spinal Circuits Also Induces Dorsal Horn Activity.
Investigate whether electrical stimulation of the spinal cord adapted to trigger locomotor patterns additionally influences dorsal horn networks. An in vitro model of isolated neonatal rat spinal cord was used to repetitively deliver electrical stimuli to lumbar dorsal roots and record from homolateral lumbar dorsal roots and ventral roots. Repetitive electrical lumbar dorsal root stimulation can affect both locomotor rhythms derived from ventral neuronal circuits and activity from dorsal neuronal circuits. These data suggest that neuro-electrostimulation protocols can simultaneously activate functionally distinct spinal neuronal circuits.


Intracellular chloride in retinal neurons: measurement and meaning.
Intracellular chloride activity measurements were obtained from mudpuppy retinal neurons using dual microelectrodes, one of which was made chloride-selective by filling the tip with chloride liquid ion exchange resin. In addition ionic substitution experiments were carried out in the perfused retina-eyecup preparation of the mudpuppy. A comparison of the membrane potential and calculated chloride equilibrium potential shows that retinal neurons differ in relative transmembrane chloride distribution. Ganglion cells have an ECl more negative than the resting membrane potential, whereas amacrine cells have a passive distribution of chloride. Horizontal cells have chloride distributed such that an increase in chloride conductance is depolarizing. On-bipolars have a chloride distribution similar to that of horizontal cells whereas off-bipolars show either passive distribution or some chloride accumulation. These findings are consistent with the idea that chloride ions may play a role as a depolarizing driving force for electrogenic activity of horizontal cells and on-bipolars. Results with Cl substitution experiments are consistent with this interpretation.


Fabricating polyacrylamide microbeads by inverse emulsification to mimic the size and elasticity of living cells.
Inverse emulsification was used to fabricate polyacrylamide (PAAm) microbeads with size and elastic properties similar to typical, mammalian cells. These biomimicking microbeads could be fluorescently stained and functionalized with a collagen type-I coating, post-polymerization, for tracking bead locations and promoting cell recognition/binding, respectively. By occupying a previously unfilled range of sizes and mechanical properties, these microbeads may find unique use in both biomedical and materials applications.


Characterization of anti-acetylcholine receptor antibody activity in patients with anti-mitochondrial antibodies.
Antibodies binding to the acetylcholine receptor of human skeletal muscle were found in patients with different kinds of anti-mitochondrial antibodies. In patients with primary biliary cirrhosis (PBC), the antibody activity was found in monomeric and pentameric IgM as well as in IgG, whereas patients with other kinds of anti-mitochondrial antibodies had anti-receptor antibodies of predominantly IgG class. Mice transfused with immunoglobulins from patients with PBC showed a reduction of skeletal muscle receptors comparable to that found in mice who had received immunoglobulins from myasthenia gravis (MG) patients. The antibody affinity was of the same order of magnitude in MG and PBC but antibodies with multiple affinities were more common in PBC. In PBC, the anti-receptor antibody associated idiotype repertoire was markedly different from that found in MG.


Formation of hydrophobic drug nanoparticles via ambient solvent evaporation facilitated by branched diblock copolymers.
Hydrophobic drug nanoparticles have been prepared by ambient solvent evaporation from ethanol at room temperature. Poly(ethylene glycol)-b-(N-isopropylacrylamide) (PEG-b-PNIPAm) branched diblock copolymers are employed to prevent drug crystallization during solvent evaporation and to stabilize the drug nanoparticles once suspended in aqueous media. After the initial solvent evaporation the dry materials obtained exhibit excellent stability during storage and can be readily dissolved in water to produce aqueous drug nanoparticles suspensions. Among the hydrophobic compounds investigated, Ketoprofen nanoparticles (Dh≈200nm, stable up to 9 months in solution) can be produced with a drug suspension yield of 96% at a drug:polymer ratio of 0.33:1 or a drug suspension yield of 80% at a drug:polymer ratio of 1:1. UV-vis spectroscopy has been used to determine the yield of drug suspended in aqueous media while cryo-TEM, dynamic light scattering (DLS) and powder x-ray diffraction (PXRD) are used to characterize the drug nanoparticles prepared.


Complex genitourinary duplication affecting neurourologic and urodynamic findings: report of a case and review of the literature.
Complete duplication of the bladder and urethra is a rare congenital anomaly and usually occurs in association with other organ anomalies. We report a case of complete bladder duplication associated with multiple non-genitourinary anomalies. A 10-year-old girl presented with urinary incontinence and recurrent episodes of febrile urinary tract infections. Simultaneous right and left bladder urodynamic study was performed and revealed bilateral decreased bladder compliance associated with hyperreflexia. The patient underwent reconstructive surgery with combination of the 2 bladders and closure of the right incompetent bladder neck. Management of bladder duplication is directed towards creating an unobstructed urinary tract, preventing infections, and achieving urinary continence. Neurourologic and urodynamic assessment is of utmost importance especially when concomitant spinal anomaly exists. Furthermore, these patients should be observed lifelong as alteration in bladder function may occur.


Patient education after amputation: systematic review and experts' opinions.
To perform a systematic review of the literature regarding amputee self-care, and analyze current experts' opinions. The research in Medline and Cochrane Library databases was performed using the keywords "amputee self-care", "amputee health care", "amputee education", and "amputee health management". The methodological quality of the articles was assessed using four levels of evidence and three guideline grades (A: strong; B: moderate; C: poor). One prospective randomized controlled study confirm the level of evidence of self-care amputee persons with grade B, which is similar others chronic diseases self-care. Self-care of amputee persons contributes to improve functional status, depressive syndrome, and also health-related quality of life. A review of the patients' needs and expectations in self-care amputee persons has been established thanks to the presence of qualitative focus group study. A multidisciplinary self-care of amputee persons can be recommended. Regarding literature date, the level of evidence of self-care amputee persons is moderate (grade B). Experts groups are currently working on a self-care amputee persons guideline book in order to standardize practicing and programs in the physical medicine and rehabilitation departments.


Complete genome sequence and evolution analysis of a columbid herpesvirus type 1 from feral pigeon in China.
Here, we report the genome sequence of a feral pigeon alphaherpesvirus (columbid herpesvirus type 1, CoHV-1), strain HLJ, and compare it with other avian alphaherpesviruses. The CoHV-1 strain HLJ genome is 204,237 bp in length and encodes approximately 130 putative protein-coding genes. Phylogenetically, CoHV-1 complete genome resides in a monophyletic group with the falconid herpesvirus type 1 (FaHV-1) genome, distant from other alphaherpesviruses. Interestingly, the evolutionary analysis of partial genes of CoHV-1 isolated from different organisms and areas (currently accessible on GenBank) indicates that the CoHV-1 HLJ strain isolated from pigeon (Columba livia) is closely related to the strains isolated from peregrine falcon (Falco peregrinus) in Poland and owl (Bubo virginianus) in USA. These results may suggest possible transmission of the virus between different organisms and different geographic areas.


Deconvolution of pulse trains with the L0 penalty.
The output of many instruments can be modeled as a convolution of an impulse response and a series of sharp spikes. Deconvolution considers the inverse problem: estimate the input spike train from an observed (noisy) output signal. We approach this task as a linear inverse problem, solved using penalized regression. We propose the use of an L(0) penalty and compare it with the more common L(2) and L(1) penalties. In all cases a simple and iterative weighted regression procedure can be used. The model is extended with a smooth component to handle drifting baselines. Application to three different data sets shows excellent results.


Insulin therapy normalizes reduced myocardial β-adrenoceptors at both the onset and after sustained hyperglycemia in diabetic rats.
Reduced cardiac β-adrenoceptors (β-AR) and cardiovascular (CV) dysfunction occur in diabetes mellitus (DM) and can be normalized by insulin. It is unclear how the duration of untreated hyperglycemia prior to intervention impacts insulin's effects. This study assesses insulin's effect on reduced myocardial β-AR and CV function, comparing insulin therapy at the onset of hyperglycemia and after a sustained period of hyperglycemia in streptozotocin (STZ) rats. Ex vivo biodistribution experiments with [(3)H]CGP12177 were performed in high-fat fed STZ rats after 8 weeks of hyperglycemia evaluating cardiac β-AR expression. Western blotting of β-AR subtypes was completed in parallel. Serial echocardiography at 0, 6, and 8 weeks post-STZ investigated CV function. Sub-groups of hyperglycemic rats were treated with insulin early, at 1 week post-STZ (InsE) for 7 weeks, or late at 6 weeks post-STZ (InsL) for 2 weeks to observe how the duration of hyperglycemia prior to insulin impacts its effects. Reduced myocardial [(3)H]CGP12177 binding occurred 8 weeks post-STZ in hyperglycemics, but was normal in both insulin treatments. Western blotting supported reduced β1-AR in hyperglycemics, but not in either treatment. InsE and InsL treatments improved prolonged mitral valve deceleration (MVD) observed in hyperglycemic animals, but hyperglycemic and InsL still displayed reduced heart rates (HR). This work supports that glycemic control with insulin normalizes cardiac β-AR effectively regardless of prior hyperglycemia but HR may not recover as readily, indirectly supporting the utility of [(11)C]CGP12177 positron emission tomography (PET) in assessing cardiac β-AR and their modulation with glycemic therapy.


Histaminergic neurons mediate restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus.
The role of histamine in mediating restraint stress-induced increases in the activity of noradrenergic neurons projecting to the hypothalamus was evaluated in male rats. Noradrenergic neuronal activity was estimated by measuring concentrations of the norepinephrine metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) in the paraventricular and medial preoptic nuclei which contain terminals of these neurons. Placement of rats within restraining tubes rapidly increased MHPG but not norepinephrine concentrations in the paraventricular and medial preoptic nuclei. Depletion of neuronal histamine by alpha-fluoromethylhistidine and antagonism of H1 receptors by mepyramine attenuated, whereas blockade of H2 receptors by zolantidine did not prevent the stress-induced increases in MHPG concentrations. Neither mepyramine nor zolantidine affected MHPG concentrations in hypothalamic regions of nonstressed rats. These results indicate that histaminergic neurons contribute to the stress-induced increase the activity of noradrenergic neurons projecting to the hypothalamus via an action at H1 receptors.


Morphometric Evaluation of Bony Nasolacrimal Canal in a Caucasian Population with Primary Acquired Nasolacrimal Duct Obstruction: A Multidetector Computed Tomography Study.
The bony nasolacrimal duct (BNLD) morphology as a contributory factor in primary acquired nasolacrimal duct obstruction (PANDO) is still controversial. The objectives of this study were to evaluate the morphometric differences of BNLDs in unilateral PANDO patients between PANDO and non-PANDO sides, as compared with the control group using multidetector computed tomography (CT). Bilateral BNLDs in 39 unilateral PANDO patients and 36 control subjects were retrospectively reviewed. CT images with 0.5-mm thickness were obtained with a 64-slice scanner. The length, volume, coronal orientation type, sagittal orientation angle of BNLD, and relative lacrimal sac-BNLD angle were assessed. The entrance, minimum and distal end transverse diameters (TD) of BNLD was investigated. The mean minimum and distal end BNLD TDs measurements were significantly narrower in PANDO patients, both in PANDO and non-PANDO sides, as compared with the control group (p < 0.001 and p = 0.040, respectively); however, there were no significant differences between PANDO and non-PANDO sides within PANDO patients. The length, entrance TD, volume, coronal orientation type, sagittal orientation angle of BNLD, and relative lacrimal sac-BNLD angle were not significantly different between PANDO patients and control subjects, as well as between PANDO and non-PANDO sides within PANDO patients. The narrow mean minimum and distal end BNLD TD in PANDO patients, in both PANDO and non-PANDO sides, may be associated with PANDO development. The lack of difference between PANDO and non-PANDO sides within PANDO patients and some overlap between PANDO patients and control subjects suggest that narrow BNLD is not the sole factor.


Xuesaitong injection (lyophilized) combined with aspirin and clopidogrel protect against focal cerebral ischemic/reperfusion injury in rats by suppressing oxidative stress and inflammation and regulating the NOX2/IL-6/STAT3 pathway.
Combination of aspirin (ASA) and clopidogrel (CLP) [dual antiplatelet therapy (DAPT)] has been limited in reducing early recurrent stroke events. Xuesaitong injection (lyophilized) (XST) made of total saponins from P. notoginseng, which significantly improves cerebral circulation and has been widely used in clinical applications for decades to treat and prevent ischemic stroke. Here, we confirmed the protective effect and mechanism of XST combined with DAPT (XST+ASA+CLP) on cerebral ischemia/reperfusion injury, exploring their better pharmacological action for clinical patients. Sprague-Dawley rats (SD rats) (n=9 in each group) were randomly assigned to three groups and pretreated with XST, ASA+CLP, or XST+ASA+CLP for 7 days. Then rats were subjected to 2 h of middle cerebral artery occlusion (MCAO) followed by reperfusion for 24 h. Therapeutic effect of XST+ASA+CLP was measured by infarct volume, neurological behavior and regional cerebral blood flow (rCBF). Inhibition of neuronal apoptosis and glial cells was determined by immunofluorescent staining. We studied the protein levels of neurotrophic factors, neuroplasticity-related factors, oxidative stress indicators and inflammatory factors by ELISA assay. XST+ASA+CLP group showed significant reduction in infarct volumes and neurological deficit scores. XST+ASA+CLP group also had higher levels in rCBF and synaptic growth, and showed remarkable inhibition of microglia and astrocytes activation and the neuronal apoptosis. In addition, XST+ASA+CLP group had lower levels of NADPH, protein carbonyl, 4-hydroxynonenal (4-HNE), 8-hydroxydeoxyguanosine (8-OHdG) and several inflammatory cytokines. Moreover, XST+ASA+CLP group also had lower levels of NOX2, inducible nitric oxide synthase (iNOS), interleukin (IL)-6, and p-STAT3/STAT3. These results demonstrate that a combination of XST, ASA, and CLP effectively protected rats against middle cerebral artery occlusion/reperfusion (MCAO/R) injury by suppressing the NOX2/IL-6/ STAT3 pathway. These novel findings provide theoretical basis and experimental evidence for the rationality of clinical combined use of drugs in the treatment of ischemic stroke.


Climate change effects on denitrification performance of woodchip bioreactors treating agricultural tile drainage.
Denitrifying woodchip bioreactors (WBRs) are a nature-based technology that are increasingly used to control nonpoint source nitrate (NO3-) pollution in agricultural catchments. The treatment effectiveness of WBRs depends on temperature and hydraulic retention time (HRT), both of which are affected by climate change. Warmer temperatures will increase microbial denitrification rates, but the extent to which the resulting benefits to treatment performance may be offset by intensified precipitation and shorter HRTs is not clear. Here, we use three years of monitoring data from a WBR in Central New York State to train an integrated hydrologic-biokinetic model describing links among temperature, precipitation, bioreactor discharge, denitrification kinetics, and NO3- removal efficiencies. Effects of climate warming are assessed by first training a stochastic weather generator with eleven years of weather data from our field site, and then adjusting the distribution of precipitation intensities according to the Clausius-Clapeyron relationship between water vapor and temperature. Modeling results indicate, in our system, faster denitrification rates will outweigh the influence of intensified precipitation and discharge under warming, leading to net improvements in NO3- load reductions. Median cumulative NO3- load reductions at our study site from May - October are projected to increase from 21.7% (interquartile range 17.4%-26.1%) under baseline hydro-climate to 41.0% (interquartile range 32.6-47.1%) with a + 4 °C change in mean air temperature. This improved performance under climate warming is driven by strong nonlinear dependence of NO3- removal rates on temperature. Temperature sensitivity may increase with woodchip age and lead to stronger temperature-response in systems like this one with a highly aged woodchip matrix. While the impacts of hydro-climatic change on WBR performance will depend on site-specific properties, this hydrologic-biokinetic modeling approach provides a framework for assessing climate impacts on the effectiveness of WBRs and other denitrifying nature-based systems.


High-Intensity Progressive Rehabilitation Versus Routine Rehabilitation After Total Knee Arthroplasty: A Randomized Controlled Trial.
This study aimed to compare the effectiveness of high-intensity progressive rehabilitation training with routine training in the early treatment of patients undergoing total knee arthroplasty. There were 78 patients who underwent total knee arthroplasty and were randomized into high-intensity progressive training and routine rehabilitation training groups (RRT). The primary outcome measures were the American Hospital for Special Surgery Knee Score (HSS), with secondary outcomes including patient satisfaction, visual analog pain score, first time of standing after surgery, 6-minute walk test, 36-Item Short Form Survey (SF-36), and length of hospital stay. The incidence of postoperative complications were recorded. The HSS scores were higher in the intervention group at 2 weeks, 3 months, and 12 months postoperatively (P < .001). The RRT group had higher visual analog pain scores than the intervention group at 24 hours, 3 days, and 2 weeks after surgery (P < .001). The intervention group had an earlier the first time of standing after surgery and a longer 6-minute walk test distance (P < .001, P = .028, P < .001, P < .001). Patient satisfaction was higher in the intervention group, with a higher quality of life rating at 3 months postoperatively (P < .001). However, 1 year after surgery, the 2 groups had no significant differences in mental component summaries. The length of hospital stay was shorter in the intervention group than in the RRT group. Compared to routine training, high-intensity progressive rehabilitation training is more effective. It reduces postoperative patient pain, accelerates recovery of joint function, increases patient satisfaction, improves quality of life, shortens hospital stays, and promotes rapid recovery.


A case of bilateral diffuse uveal melanocytic proliferation with secondary angle closure caused by ciliary body thickening.
To describe a case of bilateral diffuse uveal melanocytic proliferation (BDUMP) with secondary angle closure caused by ciliary body thickening accompanied by intraocular pressure (IOP) elevation after mydriasis. A 55-year-old woman with a history of ovarian cancer had blurred vision in both eyes. Fundus examination revealed multiple patchy lesions in both eyes and a nevus-like elevated lesion in the right eye. Anterior segment optical coherence tomography (AS-OCT) and ultrasound biomicroscopy (UBM) demonstrated angle closure resulting from ciliary body thickening. After mydriasis, the IOP was elevated in both eyes. Instillation of a miotic drug successfully reversed the IOP to normal levels. BDUMP caused secondary angle closure in both eyes, presumably due to thickening of the entire ciliary body. AS-OCT and UBM were advantageous for analyzing the morphology of the anterior eye segment in BDUMP. Clinicians should be aware of the possibility of angle closure during the management of patients with BDUMP.


Cytokines and signal transduction.
Many studies have characterized the role of growth factors in multiple myeloma (MM) pathogenesis and have derived novel therapies to improve patient outcome based upon targeting cytokines and their signaling cascades both in the MM cell and in the bone-marrow (BM) microenvironment. These cytokines include interleukin 6 (IL-6), insulin-like growth factor 1 (IGF-1), vascular endothelial growth factor (VEGF), tumor necrosis factor alpha (TNF-alpha), transforming growth factor beta (TGF-beta), stromal cell-derived factor 1alpha (SDF-1alpha), IL-21, B-cell stimulating factor 3 (BSF-3) and fibroblast growth factor (FGF). These cytokines are secreted from stromal cells (SCs), endothelial cells and/or osteoclasts, and promote MM cell growth, survival and migration, as well as paracrine cytokine secretion and angiogenesis in the BM milieu. Thus inhibition of signaling cascades induced by these cytokine provides rationale for a therapeutic option for MM.


Subunit composition of the molybdate-stabilized "8-9 S" nontransformed estradiol receptor purified from calf uterus.
The structure of the calf uterus nontransformed molybdate-stabilized estradiol receptor (ER) has been investigated using affinity labeling with tamoxifen aziridine and several monoclonal antibodies directed either against the steroid binding protein (Mr approximately 65,000) or against the heat shock protein of Mr approximately 90,000 (hsp 90). The purification was performed using affinity chromatography and a DEAE-Sephacel column. The [3H] estradiol-ER complex was obtained as a well-defined radioactive peak, the specific activity varying between 1,600 and 3,400 pmol/mg of protein. The purified ER sediments in glycerol gradients at 9.4 S +/- 0.2 (n = 5) and at 8.1 S +/- 0.2 (n = 15) in a 0.15 M KCl containing gradient ("8-9 S" ER). From a measured Stokes radius of 7.4 +/- 0.2 nm (n = 12), an Mr of approximately 300,000 has been calculated. Studies of the purified 8-9 S ER by glycerol gradient centrifugation and by "twin antibody" assay with the JS34/32 anti-ER monoclonal antibody suggest the presence of two binding subunits in the nontransformed molecular complex. Results of immunological analysis with polyclonal and several monoclonal antibodies against hsp 90 suggest the association of two molecules of this protein to the two steroid binding subunits. In high salt medium (0.4 M KCl), the purified ER sediments at 5.2 +/- 0.3 (n = 8), has a Stokes radius of 5.7 nm +/- 0.1 (n = 2) and the Mr is approximately 129,000, values expected for a homodimer consisting of two hormone-binding subunits (Mr approximately 65,000), a result confirmed by glycerol gradient centrifugation experiments, using the monoclonal antibody JS34/32. The relationship between the nontransformed 8-9 S ER and the transformed 5 S-ER forms are discussed, the simplest possibility being the release of the already formed homodimeric ER from 8-9 S ER during transformation.