Irreversible immune reactions following keratoplasty. Retrospective clinical and histological evaluation of graft failure in a material of 206 consecutive eyes.
A total of 16/206 eyes in 14/186 patients developed irreversible immune reactions. 15 of the rejected eyes belonged to the 'classical' risk groups, i.e. systemic immune disorders (3/3), metaherpetic keratitis (6/41), pseudophakic bullous keratopathy with inflammation (2/6), non herpetic keratitis with vessel invasion (1/23) and 3 regrafts not included in these groups (a total of 7/31 regrafted eyes rejected). Only 1 rejection occurred in the low-risk groups: an aphakic eye with bullous keratopathy. Histopathological examination revealed that discs which later developed irreversible immune reactions had invariably been grafted in eyes which had vascular invasion and/or inflammation of the recipient cornea. In all, 55/206 eyes ended up with opaque grafts, i.e. irreversible immune reactions were responsible for about one third to one-quarter of the graft failures in the present material. The irreversible immune reactions in the material must be considered 'minimum values', since possible abortive, torpid immune reactions may have escaped recording.


Relationship between fluoride content in bones and the age in European elk (Alces alces L.).
The relation between fluoride content in bones (jaws) and the age of elks living in Poland in areas of relatively low pollution by industrial emissions was studied. Multiple regression analysis was performed by making use of 11 mathematical models. The relationship between fluoride content in bones and the animals age is best described by square root and linear models.


Host-directed editing of the SARS-CoV-2 genome.
The extensive sequence data generated from SARS-CoV-2 during the 2020 pandemic has facilitated the study of viral genome evolution over a brief period of time. This has highlighted instances of directional mutation pressures exerted on the SARS-CoV-2 genome from host antiviral defense systems. In this brief review we describe three such human defense mechanisms, the apolipoprotein B mRNA editing catalytic polypeptide-like proteins (APOBEC), adenosine deaminase acting on RNA proteins (ADAR), and reactive oxygen species (ROS), and discuss their potential implications on SARS-CoV-2 evolution.


Interaction of vascular plants and vesicular-arbuscular mycorrhizal fungi across a soil moisture-nutrient gradient.
Abundance and distribution of vascular plants and vesicular-arbuscular mycorrhizal (VAM) fungi across a soil moisture-nutrient gradient were studied at a single site. Vegetation on the site varied from a dry mesic paririe dominated by little bluestem (Schizachyrium scoparium) to emergent aquatic vegetation dominated by cattail (Typha latifolia) and water smartweed (Polygonum hydropiperoides). Plant cover, VAM spore abundance, plant species richness, and number of VAM fungi represented as spores, had significant positive correlations with each other and with percent organic matter. The plant and VAM spore variables had significant negative correlations with soil pH and available Ca, Mg, P and gravimetric soil moisture. Using stepwise multiple regression, Ca was found to be the best predictor of spore abundance. Test for association between plant species and VAM fungal spores indicated that the spores of Glomus caledonium are associated with plants from dry, nutrient poor sites and spores of gigaspora gigantea are positively associated with plants occurring on the wet, relatively nutrient rich sites. Glomus fasciculatum was the most abundant and widely distributed VAM fungus and it had more positive associations with endophyte hosts than the other VAM fungi. We found no relationship between beta niche breadth of plant species and the presence or absence of mycorrhizal infection. However, our data suggest that some plant species may vary with respect to their infection status depending upon soil moisture conditions that may fluctuate seasonally or annually to favor or hinder VAM associations.


Subretinal strands. Tissue culture and histological study.
Subretinal strands in proliferative vitreoretinopathy removed during vitreous surgery in ten cases were studied histologically; tissue culture was taken from five of the ten cases to obtain more material for investigation. Tissue culture was successful in all five cases. The cultured tissue just next to the original strand preserved the characteristics of the original tissue, whereas the portion distal from the original strand did not. Definite and/or suspected retinal pigment epithelial cells (RPE) were found in seven of ten original strands and four of five samples of cultured material. RPE were considered to be a predominant component of subretinal strands.


Regional brain uptake of 2-deoxyglucose in N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced parkinsonism in the macaque monkey.
This preliminary report describes application of the 2-deoxyglucose (2DG) autoradiographic technique to study regional changes in brain metabolism in experimental parkinsonism, induced in the monkey by administration of the neurotoxin MPTP. In one monkey, rendered severely parkinsonian by MPTP, there was a marked increase in the uptake of 2DG in the globus pallidus (both medial and lateral segments) and in the ventral anterior and ventral lateral thalamic nuclei, in comparison to non-parkinsonian animals. Increased uptake of 2DG in the globus pallidus may reflect increased activity of striatopallidal synapses secondary to loss of nigrostriatal dopaminergic neurones. The findings are in sharp contrast to our observations on regional brain metabolism in experimental choreiform dyskinesia in the monkey.


Multi-residue determination of pesticides in vegetables and assessment of human health risks in Western Himalayan region of India.
This study was aimed to determine pesticides concentrations in fresh vegetables and assess human health risks in North-Western Himalayan region of India. Vegetable samples (n = 300) collected randomly from different agro-climatic zones were analyzed for 19 pesticides using gas chromatography. Pesticide residues were detected in 116 samples, of which 49 samples exceeded maximum permissible limits established by European Commission. Hexaconazole was most frequently detected in 9.3% samples followed by aldrin (8.3%), alachlor (5.3%), bifenthrin (4.3%), chlorpyrifos (3.7%), metribuzin (2.7%), β-endosulfan, ethion, β-HCH (2%, each), γ-HCH (1.3%), α-HCH, δ-HCH, malathion, heptachlor (1%, each), and α-endosulfan, pendimethalin in 0.7% samples. Human health risk assessment revealed that the percent contribution to acceptable daily intakes of pesticides via dietary intake of vegetables ranged from 0.014 to 39.4% in children and 0.003 to 9.85% in adults. Although hazard index values were < 1 but considering the concentrations of detected pesticide in samples, children were found to be at more risk. Since pragmatic investigations on occurrence of pesticides in vegetables and human health risk assessment from study area have not yet been worked out, so, this study highlights the importance of adopting good agricultural practices, awareness on food safety, monitoring of harmful chemicals in food commodities, and execution of food safety regulations to safeguard environmental and human health.


In vitro and in vivo assessment of the effect of biodegradable magnesium alloys on osteogenesis.
Magnesium (Mg) and some of its alloys are considered promising biodegradable metallic biomaterials for bone implant applications. The osteogenesis effect of Mg alloys is widely reported; however, the underlying mechanisms are still not clear. In this study, pure Mg, Mg-3Zn, and Mg-2Zn-1Mn were prepared, and their degradation behavior, biocompatibility, and osteogenesis effect were systematically assessed both in vitro and in vivo. Primary rat bone marrow-derived mesenchymal stem cells (BMSCs) were used to evaluate the biocompatibility of the prepared Mg alloys, and a rat femur fracture model was used to assess the stimulating effect of these alloys on bone-tissue formation. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. Extracts of the three materials showed significant stimulating effects on osteogenic differentiation of BMSCs along with non-cytotoxicity. Implantation of Mg-2Zn-1Mn wires into the femur of rats demonstrated superior histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. Moreover, the results of both in vitro and in vivo assessments demonstrated that bone morphogenetic proteins and fibroblast growth factor receptors are involved in the stimulating effect of Mg alloys. STATEMENT OF SIGNIFICANCE: This work reports the degradation behavior, biocompatibility, and osteogenic effect of pure Mg and Mg-3Zn and Mg-2Zn-1Mn alloys in both in vitro and in vivo conditions. Mg-2Zn-1Mn showed higher corrosion resistance and more stable degradation behavior than pure Mg and Mg-3Zn. The extracts of the three materials showed a significant stimulating effect on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (BMSCs) along with non-cytotoxicity. Mg-2Zn-1Mn wires implanted into the femur of rats showed good histocompatibility, stable degradation, and notable promotion of osteogenesis without systemic toxicity. The results of the present study suggest that bone morphogenetic proteins (BMPs) and fibroblast growth factor receptors (FGFRs) are involved in the stimulating effect of Mg alloys on osteogenesis.


Impact of Temporary Percutaneous Mechanical Circulatory Support Before Transplantation in the 2018 Heart Allocation System.
This analysis sought to investigate the waitlist and post-transplant outcomes of individuals bridged to transplantation by using temporary percutaneous endovascular mechanical circulatory support (tMCS) through a status 2 designation (cardiogenic shock and exception). The 2018 donor heart allocation policy change granted a status 2 designation to patients supported with tMCS. Adult patients in the United Network for Organ Sharing registry after October 18, 2018 who received a status 2 designation for tMCS were included and grouped by their status 2 criteria: cardiogenic shock with hemodynamic criteria (CS-HD), cardiogenic shock without hemodynamic criteria before tMCS (CS-woHD), and exception. Baseline characteristics, waitlist events (death and delisting), and post-transplant outcomes were compared. A total of 2,279 patients met inclusion criteria: 68.6% (n = 1,564) with CS-HD, 3.2% (n = 73) with CS-woHD, and 28.2% (n = 642) with exceptions. A total of 64.2% of patients underwent heart transplantation within 14 days of status 2 listing or upgrade, and 1.9% died or were delisted for worsening clinical condition. Among the 35.8% who did not undergo transplantation following 14 days, only 2.8% went on to receive a left ventricular assist device (LVAD). The 30-day transplantation likelihood was similar among groups: 80.1% for the CS-HD group vs 79.7% for the exception group vs 73.3% for the CS-woHD group; P = 0.31. However, patients who met criteria for CS-woHD had 2.3-fold greater risk of death or delisting (95% CI: 1.10-4.75; P = 0.03) compared with CS-HD patients after multivariable adjustment. Pre-tMCS hemodynamics were not associated with adverse waitlist events. The use of tMCS is an efficient, safe, and effective strategy as a bridge to transplantation; however, patients with CS-woHD may represent a high-risk cohort. Transition to a durable LVAD was a rare event in this group.


Mechanisms and performance of cellulose nanocrystals Pickering emulsion chitosan coatings for reducing ethylene production and physiological disorders in postharvest 'Bartlett' pears (Pyrus communis L.) during cold storage.
Pickering emulsion coating (CNCP-CH) composed of oleic acid (OA, 1, 2, and 3%, w/w), cellulose nanocrystal (CNC, 0.1, 0.3, and 0.5%, w/w), and 2% chitosan (CH) was optimized for high emulsion stability. It was found that OA concentration played significant role on emulsion stability. Increasing OA from 1 to 3% reduced emulsion stability ~43%, indicated by the thickness of separated cream layer in the emulsion. 'Bartlett' pears (Pyrus communis L.) coated by CNCP-CH containing 1% OA showed significantly reduced ethylene production than that coated with 2% and 3% OA at 1-month of accelerated cold storage at 1.7 °C. The superficial scald on pear peels was only observed on fruit coated by CNCP-CH with 3% OA, but not that with 1% or 2% OA. Therefore, CNCP-CH coating with 1% OA, 0.1% CNC, and 2% CH was suggested for delaying ripening and superficial scald of 'Bartlett' pears during the long-term cold storage.


What have we learned about uterine contractions and preterm birth? The HUAM Prediction Study.
Measurement of uterine contraction frequency has been employed as a screening test to identify women with increased risk of preterm birth, and as an aid in the early diagnosis of preterm labor. The National Institute of Child Health and Human Development Maternal-Fetal Medicine Units (NICHD MFMU) Network performed a prospective, blinded observational study of uterine contraction frequency to detect and predict preterm labor and birth, respectively. The goal of the study was to assess the sensitivity, specificity, and positive and negative predictive value of various measures of uterine contraction frequency. Data collected from 306 women revealed that contraction frequency was significantly greater in women who would ultimately deliver before rather than after 35 weeks' gestation. However, both sensitivity and positive predictive value of any measure of contraction frequency to predict preterm birth were poor. Contraction frequency did not increase significantly within 1 or 2 weeks of an episode of preterm labor. These results serve to explain the absence of an association between contraction-based surveillance and preterm birth in randomized trials conducted in women at risk of preterm birth.


Rapid refilling of Ca2+ stores in macrophages stimulated by ATP involves the sequential activation of phospholipase D and protein kinase C.
Ca2+ movements between intracellular stores, the cytoplasm and external solution were analysed in murine peritoneal macrophages stimulated by various agonists. The Ca2+ content of intracellular stores was estimated from the amplitude of Ca(2+)-transients elicited by ionomycin applied in Ca(2+)-free solution. Both uridine 5'-triphosphate (UTP) and platelet-activating factor (PAF) triggered the release of Ca2+ followed by a sustained influx, during which intracellular stores remained totally empty. In contrast, in the continuous presence of adenosine 5'-triphosphate (ATP), Ca2+ was initially released and then rapidly sequestered again by the stores. ATP-induced store refilling was not related to cell depolarization or to an increase in the intracellular Na+ concentration (two specific consequences of ATP stimulation which are not induced by PAF and UTP). Store refilling was not caused by a signal that ATP would fail to induce (e.g. as a result of receptor desensitization), but was positively controlled by ATP, even in the simultaneous presence of a concentration of PAF which, on its own, would have caused a persistent store depletion. The hypothesis that the signal delivered by ATP involves the sequential activation of phospholipase D and protein kinase C is consistent with the present pharmacological evidence. However, although we found conditions in which Ca2+ stores did not refill in the presence of ATP, this maintained store depletion was not accompanied by a sustained Ca2+ response similar to that elicited by PAF or UTP, suggesting that store depletion is a condition which is necessary, but not sufficient, for inducing Ca2+ influx.


Pulmonary aspects of chronic liver disease and liver transplantation.
A vast spectrum of pulmonary pathologic conditions occurs in association with chronic liver diseases, and clinically important manifestations, such as arterial hypoxemia, can result. Both pulmonary vascular and parenchymal abnormalities can contribute to the dysfunction, as evidenced by results of pulmonary function tests and gas exchange studies. The clinical implications of identifying such pulmonary problems range from alleviation of symptoms, especially dyspnea, to comprehensive assessment of patients before and after liver transplantation. Physicians should be aware of these potential pulmonary disorders that can complicate liver disease and liver transplantation so that management of affected patients can be improved.


Performance and allocation patterns of the perennial herb, Plantago lanceolata, in response to simulated herbivory and elevated CO2 environments.
We tested the prediction that plants grown in elevated CO2 environments are better able to compensate for biomass lost to herbivory than plants grown in ambient CO2 environments. The herbaceous perennial Plantago lanceolata (Plantaginaceae) was grown in either near ambient (380 ppm) or enriched (700 ppm) CO2 atmospheres, and then after 4 weeks, plants experienced either 1) no defoliation; 2) every fourth leaf removed by cutting; or 3) every other leaf removed by cutting. Plants were harvested at week 13 (9 weeks after simulated herbivory treatments). Vegetative and reproductive weights were compared, and seeds were counted, weighed, and germinated to assess viability.Plants grown in enriched CO2 environments had significantly greater shoot weights, leaf areas, and root weights, yet had significantly lower reproductive weights (i.e. stalks + spikes + seeds) and produced fewer seeds, than plants grown in ambient CO2 environments. Relative biomass allocation patterns further illustrated differences in plants grown in ambient CO2 environments. Relative biomass allocation patterns further illustrated differences in plant responses to enriched CO2 atmospheres: enriched CO2-grown plants only allocated 10% of their carbon resources to reproduction whereas ambient CO2-grown plants allocated over 20%. Effects of simulated herbivory on plant performance were much less dramatic than those induced by enriched CO2 atmospheres. Leaf area removal did not reduce shoot weights or reproductive weights of plants in either CO2 treatment relative to control plants. However, plants from both CO2 treatments experienced reductions in root weights with leaf area removal, indicating that plants compensated for lost above-ground tissues, and maintained comparable levels of reproductive output and seed viability, at the expense of root growth.


Upconversion particle-assisted NIR polymerization enables microdomain gradient photopolymerization at inter-particulate length scale.
High crosslinking and low shrinkage stress are difficult to reconcile in the preparation of performance-enhancing photopolymer materials. Here we report the unique mechanism of upconversion particles-assisted NIR polymerization (UCAP) in reducing shrinkage stress and enhancing mechanical properties of cured materials. The excited upconversion particle emit UV-vis light with gradient intensity to the surroundings, forming a domain-limited gradient photopolymerization centered on the particle, and the photopolymer grows within this domain. The curing system remains fluid until the percolated photopolymer network is formed and starts gelation at high functional group conversion, with most of the shrinkage stresses generated by the crosslinking reaction having been released prior to gelation. Longer exposures after gelation contribute to a homogeneous solidification of cured material, and polymer materials cured by UCAP exhibit high gel point conversion, low shrinkage stress and strong mechanical properties than those cured by conventional UV polymerization techniques.


Early biomarkers from dynamic contrast-enhanced magnetic resonance imaging to predict the response to antiangiogenic therapy in high-grade gliomas.
The aim of this study is to investigate whether early changes in tumor volume and perfusion measurements derived from dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) may predict response to antiangiogenic therapy in recurrent high-grade gliomas. Twenty-seven patients who received bevacizumab every 3 weeks were enrolled in the study. For each patient, three MRI scans were performed: at baseline, after the first dose, and after the fourth dose of bevacizumab. The entire tumor volume (V(tot)), as well as contrast-enhanced and noncontrast-enhanced tumor subvolumes (V(CE-T1) and V(NON-CE-T1), respectively) were outlined using post-contrast T1-weighted images as a guide for the tumor location. Histogram analysis of normalized IAUGC (nIAUGC) and transfer constant K(trans) maps were performed. Each patient was classified as a responder patient if he/she had a partial response or a stable disease or as a nonresponder patient if he/she had progressive disease. Responding patients showed a larger reduction in V(NON-CE-T1) after a single dose, compared to nonresponding patients. Tumor subvolumes with increased values of nIAUGC and K(trans), after a single dose, significantly differed between responders and nonresponders. The radiological response was found to be significantly associated to the clinical outcome. After a single dose, V(tot) was predictive of overall survival (OS), while V(CE-T1) showed a tendency of correlation with OS. Tumor subvolumes with increased nIAUGC and K(trans) showed the potential for improving the diagnostic accuracy of DCE. Early assessments of the entire tumor volume, including necrotic areas, may provide complementary information of tumor behavior in response to anti-VEGF therapies and is worth further investigation.


Pulling Together as a Community to Ensure the Quality of the Literature.
Pulling up our socks! In this Editorial, ChemMedChem Editor-in-Chief Natalia Ortúzar discusses how editors, reviewers and authors might all pull together to address the issue of reproducibility of data reported in the literature.


Quantitative Analysis for ROS-Producing Activity and Regulation of Plant NADPH Oxidases in HEK293T Cells.
Reactive oxygen species (ROS) produced by plant NADPH oxidases, respiratory burst oxidase homologs (RBOHs), play key roles in biotic and abiotic stress responses and development in plants. While properly controlled amounts of ROS function as signaling molecules, excessive accumulation of ROS can cause undesirable side effects due to their ability to oxidize DNA, lipids, and proteins. To limit the damaging consequences of unrestricted ROS accumulation, RBOH activity is tightly controlled by post-translational modifications (PTMs) and protein-protein interactions. In order to analyze these elaborate regulatory mechanisms, it is crucial to quantitatively assess the ROS-producing activity of RBOHs. Given the high endogenous ROS generation in plants, however, it can be challenging in plant cells to measure ROS production derived from specific RBOHs and to analyze the contribution of regulatory events for their activation and inactivation. Here we describe human embryonic kidney 293T (HEK293T) cells as a heterologous expression system and a useful tool to quantitatively monitor ROS production by RBOHs. This system permits the reconstitution of regulatory events to dissect the effects of Ca2+, phosphorylation, and protein-protein interactions on RBOH-dependent ROS production.


[Maxillary ridge expansion for dental implant placement with alveolar corticotomy].
Maxillary ridge transversal expansion is based on osseous plasticity obtained by corticotomy. It allows progressively for an adequate transversal intercortical diameter large enough to insert one or several dental implants. We present a pre-implant maxillary ridge transversal osseous expansion technique. Surgery is carried out under local or general anesthesia. Infiltration of a local anesthetic with adrenaline reduces bleeding and facilitates dissection. One horizontal crestal and two vertical vestibular surgical incisions are made in the mucosa. The operating site is exposed by lifting a mucoperiostic flap. Two vertical osteotomies are performed 2mm away on either side of the future implant and one horizontal crestal osteotomy. A guided bone fracture following the osteotomy lines is performed with an osteotome. An alveolar bone flange with a superior hinge is thus obtained. If implant placement is immediately possible, the implant bed is made with the osteotomes and/or drill. An osseous graft is inserted in the intercortical space around the cervical implant area and in the corticotomy zones. The mucosa is sutured on a resorbable collagen membrane. The indications are maxillary crestal thickness ranging from 1.5 to 3mm. This technique allows gaining 4 to 5.5mm of thickness on a length of up to 40 mm. Implants are often placed during the same surgery. Morbidity is limited and aesthetic prosthetic results are satisfactory.


Drivers of retention of the HIV workforce transitioned from PEPFAR support to the Uganda government payroll.
Health worker (HW) retention in the public health sector in Uganda is an enduring health system constraint. Although previous studies have examined the retention of in-service HWs, there is little research focusing on donor-recruited HWs. The objective of this study was to explore drivers of retention of the HIV workforce transitioned from PEPFAR support to the Uganda government payroll between 2015 and 2017. We conducted ten focus group discussions with HWs (n = 87) transitioned from PEPFAR support to the public sector payroll in 10 purposively selected districts across Uganda. In-depth interviews were conducted with national-level stakeholders (n = 17), district health and personnel officers (n = 15) and facility in-charges (n = 22). Data were analyzed by a hybrid approach of inductive and deductive thematic development based on the analytical framework by Schaefer and Moos regarding individual-level and organizational-context drivers. At the individual level, job security in the public sector was the most compelling driver of health worker retention. Community embeddedness of HWs in the study districts, opportunities for professional development and career growth and the ability to secure salary loans due to 'permanent and pensionable' terms of employment and the opportunity to work in 'home districts', where they could serve their 'kinsmen' were identified as enablers. HWs with prior private sector backgrounds perceived public facilities as offering more desirable challenging professional work. Organizational context enablers identified include perceptions that public facilities had relaxed supervision regimes and more flexible work environments. Work environment barriers to long-term retention include frequent stock-out of essential commodities, heavy workloads, low pay and scarcity of rental accommodation, particularly in rural Northern Uganda. Compared to mid-cadres (such as nurses and midwives), higher calibre cadres, such as physicians, pharmacists and laboratory technologists, expressed a higher affinity for seeking alternative employment in the private sector in the immediate future. Overall, job security was the most compelling driver of retention in public service for the health workforce transitioned from PEPFAR support to the Uganda government payroll. Monetary and non-monetary policy strategies are needed to enhance the retention of upper cadre HWs, particularly physicians, pharmacists and laboratory technologists in rural districts of Uganda.


Tropheryma whipplei infection (Whipple's disease) in a patient after liver transplantation.
Whipple's disease (WD) is a rare infection caused by the bacterium Tropheryma whipplei that can affect multiple organs and most commonly occurs in the immunocompetent host. Only 3 cases of WD have been reported in the setting of immunosuppression for organ transplantation. Here, we report the first case of WD, to our knowledge, in a patient after liver transplantation with comorbid graft-versus-host-disease. We discuss the diagnostic challenges in this setting and the value of electron microscopy and in situ hybridization methods for confirming the infection. WD may be under-diagnosed in immunosuppressed transplant patients because the disease can present with atypical clinical and histological features that suggest other conditions.


Development of a community orientation program (COP) as a community-based medical education method for undergraduate medical students: an experience from India.
Intra-regional cultural and linguistic differences are common in low- and middle-income countries. To sensitise undergraduate medical students to the social and contextual determinants of health to achieve the 'health for all' goal, these countries must focus on innovative teaching methods. The early introduction of a Community Orientation Program (COP) as a Community-based Medical Education (CBME) method could be a game changing strategy. In this paper the methods, evaluation, and implication of the COP in an Indian setting are described. The curriculum of the COP was developed based on the analysis, design, development, implementation, and evaluation (ADDIE) model for educational intervention. In this learner-centric and supervised educational program, the key aim was to focus on developing students' communication skills, observation power and enhancing their motivation for learning through collaborative learning. To meet the objectives of the COP, a situated learning model under the constructivism theory was adopted. Between 2016 and 2019, 557 students were trained through the COP by visiting more than 1300 households in ten villages. To supplement the students' observations in the community, more than 150 small group discussions, a health education programme for the community and summary presentations were conducted. The students' feedback indicated the need to improve the clinical examinations demonstration quality and increase the number of instruments for clinical examinations. More than 80% of students felt that the program would assist them to improve their communication skills, their understanding of the various socio-demographic factors associated with the common diseases, and it will enable them to respect the local culture during their clinical practice. Early initiation of the COP as a CBME method in the undergraduate medical curriculum in an Indian setting has shown promising results. Further evidence is required to adopt such a program routinely for under-graduate medical teaching in the low- and middle- income settings.


Cytotoxicity of 3-hydroxykynurenine in a neuronal hybrid cell line.
The toxicity of 3-hydroxykynurenine (3HK), an endogenous tryptophan metabolite which is markedly elevated in rat CNS tissue as a result of neonatal vitamin B-6 deficiency, was investigated in a neuronally derived hybrid cell line (N18-RE-105). At concentrations in excess of 100 microM, 3HK was toxic to greater than 85% of cultured cells over the course of 24 h. The time course of 3HK toxicity was studied in cultures exposed to 500 microM 3HK. Cell lysis proceeded linearly to completion in 8-12 h, but the toxic effects of exposure for 2 h were irreversible. 3HK was the most potently toxic among several related kynurenine metabolites tested. The toxic effects of 3HK exposure were markedly attenuated or abolished in the presence of either catalase or glutathione, indicating, a role of oxidative stress in 3HK toxicity.


Assessment of Fish Embryo Survival and Growth by In Situ Incubation in Acidic Boreal Streams Undergoing Biomining Effluents.
The applicability of an in situ incubation method in monitoring the effects of metal mining on early life stages of fish was evaluated by investigating the impacts of a biomining technology utilizing mine on the mortality, growth, and yolk consumption of brown trout (Salmo trutta) and whitefish (Coregonus lavaretus) embryos. Newly fertilized eggs were incubated from autumn 2014 to spring 2015 in six streams under the influence of the mine located in North-Eastern Finland and in six reference streams. Although the impacted streams clearly had elevated concentrations of several metals and sulfate, the embryonic mortality of the two species did not differ between the impacted and the reference streams. Instead, particle accumulation to some cylinders had a significant impact on the embryonic mortality of both species. In clean cylinders, mortality was higher in streams with lower minimum pH. However, low pH levels were evident in both the reference and the mine-impacted groups. The embryonic growth of neither species was impacted by the mining activities, and the growth and yolk consumption of the embryos was mainly regulated by water temperature. Surprisingly, whitefish embryos incubated in streams with lower minimum pH had larger body size. In general, the applied in situ method is applicable in boreal streams for environmental assessment and monitoring, although in our study, we did not observe a specific mining impact differing from the effects of other environmental factors related to catchment characteristics.


Characteristics of heart rate variability entropy and blood pressure during hemodialysis in patients with end-stage renal disease.
Entropy (ENT) is a newly developed measure of the complexity of heart rate variability (HRV). The aim of this study was to characterize the complexity of HRV in patients with end-stage renal disease (ESRD) and to find a possible clinical utility. Healthy subjects and patients with ESRD undergoing hemodialysis (HD) were recruited. The HD population consisted of patients with and without diabetes mellitus (DM). An electrocardiogram was recorded before HD, and blood pressure was measured during HD. The coefficients of variation of R-R intervals, high- and low-frequency components, and ratio of the low- to high-frequency components were measured as variables of HRV. The ENT was used to describe the complexity of HRV. Forty-six healthy subjects and 27 HD patients participated in this study. The ENT negatively correlated with the duration of DM (p = 0.001), systolic blood pressure (p = 0.003), and mean blood pressure (p = 0.004) before a HD session. ENT in HD patients was lower than that in healthy subjects (p < 0.01). ENT in HD patients with DM was lower than that in HD patients without DM (p < 0.01). The change in systolic blood pressure (DeltaSBP) during a HD session showed high correlations to ENT and ultrafiltration rate (UFR) of the dialyzer. The following equation was obtained: DeltaSBP = 2.25 x ENT - 2.28 x UFR - 21.27 (R2 = 0.805; p < 0.0001). ENT decreased with uremic and diabetic status. ENT also represents a possible prediction of hypotension during a HD session.


Dense bone--too much bone: radiological considerations and differential diagnosis. Part II.
In conclusion, the attempt has been made to demonstrate that three major forms of new bone formation exist: reactive, neoplastic, and the newborn or relative skeletal sclerosis in congenital (developmental) disorders. A classification of skeletal disorders has been presented and four major groups have been selected from the nine categories in this classification. These are: congenital-developmental, metabolic and endocrine, benign neoplasms and malignant neoplasms. In all four categories a large group of entities which may present with new bone (sclerosis) are listed and are discussed in some, but limited, detail. A number of these entities in each of the four categories are illustrated. Some difficulty is encountered in considering the mechanisms for the production of bony sclerosis in the group of congenital-developmental disorders. In such entities as osteopetrosis, the overproduction of cartilage cords and subsequent excessive mineralization is known to be responsible for the dense bone. However, in various skeletal dysplasias (e.g., pyknodysostosis, van Buchem disease), the exact mechanism for the development of the diffuse sclerotic process is not clearly understood. In the metabolic and endocrine category, the situation as to mechanism is less unclear in considering the reason for the development of bony sclerosis. Yet even in evaluating disorders such as renal osteodystrophy, the reactive bony sclerosis in the presence of secondary hyperparathyroidism and osteomalacia is a source of speculation with no definite proof, as yet.


Effect of protease and helicase mutations on HCV NS3 activity.
Hepatitis C virus (HCV) causes serious infections in the liver which may lead to liver cirrhosis and hepatocellular carcinoma. Non structural 3 (NS3) protein is one of the most important proteins of the virus which has protease and helicase activities. Protease activity has a crucial role in the replication and persistence of the virus. Site directed mutation was carried out in the protease region of one NS3 and another site directed mutation in the helicase region of another NS3. The expression of both mutated NS3 was compared with wild NS3. Expression of the three different NS3 types was confirmed by in situ staining and western blotting using an anti-NS3 antibody and correlated with a reduced antiviral response after treatment with interferon-α. Mutation analysis showed that the NS3 protease activity andnot the NS3 helicase was essential for the inhibition of the interferon-α response.


Relative validity of a FFQ in measuring carbohydrate fractions, dietary glycaemic index and load: exploring the effects of subject characteristics.
FFQ require validation as part of epidemiological research of diet-disease relationships. Studies exploring associations between carbohydrate type and chronic diseases are rapidly increasing, but information on the validity of carbohydrate fractions, dietary glycaemic index (GI) and the glycaemic load (GL) estimated by FFQ is scarce. Likewise, the effects of subject characteristics on FFQ validity have been poorly documented. The present study evaluates the relative validity of an 131-item FFQ in relation to two 3 d food records (FR) performed 6 months apart focusing on the intake of carbohydrate fractions, dietary GI and the GL. Furthermore, we assessed the extent to which subjects' age, education and BMI explain differences between these methods. The study sample comprised 218 men and 292 women aged 25-74 years participating in a large population-based survey in Finland. Energy-adjusted Spearman's rank correlations ranged from 0.27 (sugars) to 0.70 (lactose) for men and from 0.37 (sugars) to 0.69 (lactose) for women. On average, 73 % of the subjects were categorised into the same or adjacent distribution quintile based on the two methods. In general, the FFQ overestimated the intakes compared with FR. Especially in women, FFQ validity for some nutrients was associated with the level of intake, subjects' age and, to a lesser extent, education but not BMI. In conclusion, the FFQ appears to be reasonably valid in the assessment of carbohydrate exposure variables, but the findings show a need for adjustment of diet-disease relationships for subjects' age and education.


Tolerance to acute anxiolysis but no withdrawal anxiogenesis in mice treated chronically with 5-HT1A receptor antagonist, WAY 100635.
Anxiolytic-like activity in the mouse elevated plus-maze has recently been demonstrated for a range of compounds varying in degree of selectivity as 5-HT1A receptor antagonists. As tolerance and dependence liability are among the major clinical disadvantages of benzodiazepine therapy, the present study examined the effects of acute drug challenge on the plus-maze profiles of mice following daily treatment for 20 days with saline, chlordiazepoxide (CDP; 10.0 mg/kg) or the selective 5-HT1A receptor antagonist, WAY 100635 (0.1-1.0 mg/kg). To assess the development of physical dependence (withdrawal anxiogenesis), the study incorporated independent groups of animals tested on the maze 24 h after the final dose. Challenge with CDP or WAY 100635 produced behavioural changes indicative of anxiety reduction in mice that had received daily handling/saline for 20 days, thereby demonstrating that the chronic injection regimen per se had not compromised the acute efficacy of either agent. The absence of a similar response to acute drug challenge in mice treated chronically with CDP or WAY 100635 suggested the development of tolerance to the acute anxiolytic effects of both compounds under present test conditions. Despite these observations, however, no signs of enhanced anxiety were evident 24 h following discontinuation of chronic treatment with either compound. In a further experiment, the absence of withdrawal anxiogenesis at 24 h was replicated and extended to discontinuation periods of 36 and 48 h for both drugs. Although present results show that tolerance develops to the acute anxiolytic effects of CDP and WAY 100635 in the murine plus-maze, they also suggest that enhanced anxiety is not an inevitable consequence of abrupt cessation of chronic treatment with either compound.


Complete bulbar urethral transection with penile fracture after a gunshot injury in a child; a rare and challenging case.
Urethral injuries are infrequent, and management is challenging. We present a case of urethral transection associated with a penile fracture following gunshot injury. During the initial exploration complete urethral transection revealed with a bleeding penile fracture. With the use of an antegrade guidewire and a catheter, urethral ends aligned, and penile fracture repaired with suturing the tunica albuginea. Post-surgery urethrogram revealed stricture formation at bulbar urethra and detail of a gunshot injury was disclosed. Delayed stricture excision and end-to-end anastomosis was achieved, resulting in satisfactory urethral and penile functions.


Identification of anticoagulant activities in the salivary glands of the soft tick, Ornithodoros savignyi.
Salivary gland extracts of the sand tampan, Ornithodoros savignyi, prolonged the activated partial thromboplastin time (APTT) and prothrombin time (PT) significantly in a concentration-dependent manner. There was also a pronounced inhibition of human activated factor Xa (fXa) by salivary gland extracts. The salivary gland extracts inhibited chromogenic assays specific for both fXa and thrombin. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) of the salivary gland proteins followed by elution of specific areas or bands from a polyvinylidene difluoride (PVDF)-membrane, showed that various anticoagulant factors are present when screened by means of the APTT assay. The most active component was associated with a band of M(r) of 14 kDa. Partial purification of this component was achieved using isoelectric focusing (IEF) and size-exclusion high-performance liquid chromatography (HPLC).


Spleen-derived IFN-γ induces generation of PD-L1+-suppressive neutrophils during endotoxemia.
The immune inhibitory checkpoint molecule programmed death ligand (PD-L)-1 is increasingly recognized as an important player in the immune suppression observed in patients with sepsis, but its role has mainly been studied in monocytes. In an earlier study, we demonstrated that experimental human endotoxemia results in mobilization of a subset of PD-L1-expressing neutrophils displaying an IFN-γ-induced transcriptome profile. Herein, we identify the source of IFN-γ production during murine endotoxemia and its role in the generation of PD-L1+-suppressive neutrophils. We demonstrate that, similar to what we found in humans, murine endotoxemia results in the influx of a subset of PD-L1+ neutrophils in the circulation, and incubation of mouse neutrophils with recombinant IFN-γ profoundly increases PD-L1 expression. Furthermore, administration of anti-IFN-γ abrogated the generation of PD-L1+ neutrophils in endotoxemic mice. The critical involvement of the spleen is illustrated by the fact that splenectomy nullified circulating IFN-γ levels and substantially reduced the abundance of PD-L1+ neutrophils, whereas cotreatment with recombinant IFN-γ resulted in complete restoration of generation of PD-L1+ neutrophils in splenectomized mice. Finally, the functional importance of spleen-derived PD-L1+ neutrophils is exemplified by the finding that the profound decrease in T-lymphocyte proliferation observed in cells from endotoxemic mice was attenuated in cells from splenectomized animals. We demonstrated that spleen-derived IFN-γ induces generation of PD-L1+-suppressive neutrophils, implying that the spleen is critically involved in immune suppression during inflammatory diseases such as sepsis. Furthermore, our data suggest that IFN-γ plays a dual role by enhancing innate immunity and at the same time suppressing adaptive immune responses.


B cell function after haploidentical in utero bone marrow transplantation in a patient with severe combined immunodeficiency.
An in utero paternal CD34(+) cell transplant was performed in a T-B+NK+ SCID fetus. We report here the results of the 3-year humoral immune reconstitution study. The methods used were ApoB VNTR typing, flow cytometry, nephelometry, hemagglutination, ELISA, ELISPOT and lymphoproliferative assays. The T cells were of donor origin whereas monocytes, B and NK cells were of host origin. Peripheral B cell counts and IgM levels were normal since birth. IVIG therapy was required at 5 months of age until 2 years old. IgA levels > or =20 mg/dl were detected from month 17 post transplantation. Isohemagglutinins were present since month 8 post transplantation, the highest titers (anti-A:1/128, anti-B:1/32) were obtained at month 33 post-transplantation. After immunization with rHBsAg, circulating anti-HBsAg IgG secreting cells and a 7.8-fold increase in serum anti-HBsAg Ab were detected. We conclude that split chimerism following in utero haploidentical BMT allows complete humoral immune reconstitution in a T-B+NK+ SCID patient.


Association between angiotensin II type 1 receptor gene polymorphism and metabolic syndrome in a young female Iranian population.
The overall prevalence of obesity and metabolic syndrome (MetS) is increasing among children and adolescents and can predispose to type II diabetes mellitus and cardiovascular disease. There are reported associations between an angiotensin II type I receptor gene polymorphism (AT(1)R/A1166C) with hypertension, myocardial infarction, insulin resistance and cardiovascular disease risk. In the present study, we aimed to investigate whether the AT(1)R/A1166C polymorphism was associated with MetS among adolescent Iranian girls. A total of 350 adolescent girls aged 15-17 years from high schools and different educational zones of Mashhad city participated in this population-based, genetic association study. Of these individuals, 101 patients had MetS (defined by the NCEP-ATP III criteria); the remaining 249 age-matched girls were considered as the control group. All subjects were genotyped for the AT(1)R/A1166C polymorphism using the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique. Frequencies of the AA, AC and CC genotypes were 164 (65.9%), 80 (32.1%) and 5 (2.0%) in the control group and 79 (78.2%), 20 (19.8%) and 2 (2.0%) in patients, which were not consistent with the Hardy-Weinberg equilibrium (p <0.05 and p <0.001, respectively). Frequency of the AT(1)R C allele was found to be significantly lower in patients compared with controls (p <0.05). Our findings suggested that the 1166C allele of AT(1)R gene may be associated with a decreased risk of MetS in adolescent Iranian females.


The disruption of functional connectome gradient revealing networks imbalance in pediatric bipolar disorder.
Pediatric bipolar disorder (PBD) is a psychiatric disorder marked by alteration of brain networks. However, the understanding of these alterations in topological organization still unclear. This study aims to leverage the functional connectome gradient to examine changes in functional network hierarchy in PBD. Connectome gradients were used to scrutinize the differences between functional gradient map in PBD patients (n = 68, aged 11 to 18) and healthy controls (HC, n = 37, aged 11 to 18). The association between regional altered gradient scores and clinical factors was examined. We further used Neurosynth to determine the correlation of the cognitive terms with the PBD principal gradient changes. Global topographic alterations were exhibited in the connectome gradient in PBD patients, involving gradient variance, explanation ratio, gradient range, and gradient dispersion in the principal gradient. Regionally, PBD patients revealed that the default mode network (DMN) held the most majority of the brain areas with higher gradient scores, whereas a higher proportion of brain regions with lower gradient scores in the sensorimotor network (SMN). These regional gradient differences exhibited significant correlation with clinical features and meta-analysis terms including cognitive behavior and sensory processing. Functional connectome gradient presents a thorough investigation of large-scale networks hierarchy in PBD patients. This exhibited excessive segregation between DMN and SMN supports the theory of imbalance in top-down control and bottom-up in PBD and provides a possible biomarker for diagnostic assessment.


Investigation into the stabilization/solidification performance of Portland cement through cement clinker phases.
This research studied the influence of individual heavy metal on the hydration reactions of major cement clinker phases in order to investigate the performance of cement based stabilization/solidification (S/S) system. Tricalcium silicate (C3S) and tricalcium aluminate (C3A) had been mixed with individual heavy metal hydroxide including Zn(OH)2, Pb(OH)2 and Cu(OH)2, respectively. The influences of these heavy metal hydroxides on the hydration of C3S and C3A have been characterized by X-ray diffraction (XRD) and differential scanning calorimetry-thermogravimetry (DSC-TG). A mixture of Zn(OH)2, Pb(OH)2 and Cu(OH)2 was blended with Portland cement (PC) and evaluated through compressive strength and dynamic leach test. XRD and DSC-TG data show that all the heavy metal hydroxides (Zn(OH)2, Pb(OH)2 and Cu(OH)2) have detrimental effects on the hydration of C3A, but only Zn(OH)2 does to the C3S at early curing ages which can completely inhibit the hydration of C3S due to the formation of CaO(Zn(OH)2).2H2O. Cu6Al2O8CO(3).12H2O, Pb2Al4O4(CO3)(4).7H2O and Zn6Al2O8CO(3).12H2O are formed in all the samples containing C3A in the presence of metal hydroxides. After adding CaSO4 into C3A, the detrimental effect of heavy metals increases due to the coating effect of both calcium aluminate sulphates and heavy metal aluminate carbonates. The influence of heavy metal hydroxide on the hydration of C3S and C3A can be used to predict the S/S performance of Portland cement.


Beyond sustainable consumption practices: Linking organic food consumption to hedonic and eudaimonic well-being.
The organic food industry has significantly gained currency due to consumers being increasingly health conscious. However, more insight is needed to decipher the impact of organic food consumption on consumer well-being. Quantitative methods using a cross-sectional design were applied to collect data from 578 organic food consumers residing in South Africa. The results revealed that organic food consumption plays a central role in providing pleasure, positive emotions, a sense of accomplishment and personal growth to consumers. Moreover, the findings indicate that consumers' health consciousness significantly influences the interplay between dimensions of well-being. These findings shed important light on the scholarly debate around the influence of sustainable consumption on well-being. The study also provides crucial insights into new strategies that actors in the organic food industry as well as policymakers will use to effectively promote sustainable consumption and a healthy lifestyle.


Acute haemodynamic and humoral responses to felodipine and metoprolol in mild hypertension.
Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced systemic vascular resistance (SVR) by 40% after 30 min. The change in SVR was significantly related to age (r = -0.74). The reduction in the intraarterially measured brachial artery pressure was limited to 15/13 mmHg, due to a rise in cardiac output (CO). The tachycardia was sustained for 90 min, as was an elevation of plasma noradrenaline. There was a transient increase in stroke volume, associated with a reduction in pulmonary capillary wedge pressure, which was at least partly due to a reduced intravascular volume. In contrast to SVR, pulmonary vascular resistance was not affected by felodipine. Addition of intravascular metoprolol after 90 min decreased HR and CO and augmented SVR. The felodipine-induced rise in plasma renin activity (PRA) of 100% was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% during felodipine, whereas plasma aldosterone concentration (PAC) was not affected. Thus, acutely administered felodipine was a potent dilator of systemic but not of pulmonary arterioles, it stimulated the sympathetic nervous system, and reduced left ventricular filling pressure. The rise in plasma renin did not result in a higher plasma aldosterone level, due partly to reduced generation of angiotensin II.


Cesarean birth in the United States: epidemiology, trends, and outcomes.
The percentage of United States cesarean births increased from 20.7% in 1996 to 31.1% in 2006. Cesarean rates increased for women of all ages, race/ethnic groups, and gestational ages and in all states. Both primary and repeat cesareans have increased. Increases in primary cesareans in cases of "no indicated risk" have been more rapid than in the overall population and seem the result of changes in obstetric practice rather than changes in the medical risk profile or increases in "maternal request." Several studies note an increased risk for neonatal and maternal mortality for medically elective cesareans compared with vaginal births.


Molecular genetic species definition of Opisthorchiidae-like cercariae from Bithyniidae snails of Chany Lake (South-Western Siberia, Russia).
The studies of opisthorchiids larval stages associated with Bithyniidae snails can provide important and the most reliable data for opisthorchiidoses foci characterization due to the low mobility of such opisthorchiid's host species as Bithyniidae snails. The foci of opisthorchiosis (caused by Opisthorchis felineus) and metorchiosis (caused by Metorchis bilis) are overlapping in the basins of the Ob and Irtysh Rivers. Thus, difficulties with determining the species of cercariae significantly reduce the accuracy of epidemiological conclusions regarding opisthorchiosis, which has a much higher medical significance. Moreover, M. bilis cercariae identification is complicated by the fact that the focus of metorchiosis caused by Metorchis xanthosomus (infecting fish-eating predatory birds) occurs on the same territory. In this study, we for the first time carried out the molecular genetic identification of West-Siberian opisthorchiid cercariae to verify morphological identification and confirmed O. felineus's main association with Bithynia troschelii snail and M. bilis'-with B. tentaculata snail. Thus, our study applied a two-stage approach: the morphological identification of any opisthorchiid-like cercariae in Bithynia snails and subsequent molecular genetic precise species determination of cercariae in the reduced samples.


Expression and localization of estrogen receptor-beta in annulus cells of the human intervertebral disc and the mitogenic effect of 17-beta-estradiol in vitro.
Recent evidence suggests that estrogens exert effects in different tissues throughout the body, and that the estrogen receptor beta (ERbeta) may be important for the action of estrogen (17-beta-estradiol) on the skeleton. The cellular localization of ERbeta in the human intervertebral disc, however, has not yet been explored. Human disc tissue and cultured human disc cells were used for immunocytochemical localization of ERbeta. mRNA was isolated from cultured human disc cells, and RT-PCR amplification of ERbeta was employed to document molecular expression of this receptor. Cultured human disc cells were tested to determine if 17-beta-estradiol stimulated cell proliferation. In this report data are presented which provide evidence for ERbeta gene expression in human intervertebral disc cells in vivo and in vitro. Culture of annulus cells in the presence of 10-7 M 17-beta-estradiol significantly increased cell proliferation. These data provide new insight into the biology of cells in the annulus of the intervertebral disc.


Reliability of isometric knee extension muscle strength measurements made by a hand-held dynamometer and a belt: a comparison of two types of device.
[Purpose] The purpose of the present study was to compare the reliability of 2 hand-held dynamometers (HHD-1, 2) with different designs, by performing isometric knee muscle extension measurements two times each. [Subjects] The subjects were 40 young healthy adults. [Methods] The reliability of the measurements was examined using Bland-Altman analysis. [Results] Bland-Altman analysis found a fixed bias in measurements made by HHD-1 with an average limits of agreement (LOA) value of -2.1 kgf. For HHD-2, only random errors were detected, and the minimal detectable change (MDC) was 11.4 kgf. Fixed biases were observed between the two devices with an average LOA value of 2.2 kgf. When the bodyweight ratio was used, fixed biases were observed in measurements made by both devices, and the average value of LOA was -0.03 kgf/kg. The comparison of the two devices revealed only random errors, and MDC was 0.22 kgf/kg. [Conclusion] For HHD measurements using these two devices, the appropriate number of measurements is two times, and comparison of measurement values between the two devices should be avoided.


Significance of the prime factors regulating arsenic toxicity and associated health risk: a hypothesis-based investigation in a critically exposed population of West Bengal, India.
The suffering from arsenic toxicity is a long-standing concern in Asian countries. The role of the key factors (arsenic intake, age and sex) regulating arsenic toxicity is aimed to evaluate for a severely exposed population from Murshidabad district, West Bengal. Mean arsenic concentrations in drinking water supplied through tube well, Sajaldhara treatment plant and pipeline were observed as 208, 27 and 54 µg/l, respectively. Urinary arsenic concentration had been observed as < 3-42.1, < 3-56.2 and < 3-80 µg/l in children, teenagers and adults, respectively. Mean concentrations of hair and nail arsenic were found to be 0.84 and 2.38 mg/kg; 3.07 and 6.18 mg/kg; and 4.41 and 9.07 mg/kg, respectively, for the studied age-groups. Water arsenic was found to be associated with hair and nail (r = 0.57 and 0.60), higher than urine (r = 0.37). Arsenic deposition in biomarkers appeared to be dependent on age; however, it is independent of sex. Principal component analysis showed a direct relationship between dietary intake of arsenic and chronic biomarkers. Nail was proved as the most fitted biomarker of arsenic toxicity by Dunn's post hoc test. Monte Carlo sensitivity analysis and cluster analysis showed that the most significant factor regulating health risk is 'concentration of arsenic' than 'exposure duration', 'body weight' and 'intake rate'. The contribution of arsenic concentration towards calculated health risk was highest in teenagers (45.5-61.2%), followed by adults (47.8-49%) and children (21-27.6%). Regular and sufficient access to arsenic-safe drinking water is an immediate need for the affected population.


Harmonizing international trials of early goal-directed resuscitation for severe sepsis and septic shock: methodology of ProCESS, ARISE, and ProMISe.
To describe and compare the design of three independent but collaborating multicenter trials of early goal-directed resuscitation for severe sepsis and septic shock. We reviewed the three current trials, one each in the USA (ProCESS: protocolized care for early septic shock), Australasia (ARISE: Australasian resuscitation in sepsis evaluation), and the UK (ProMISe: protocolised management in sepsis). We used the 2010 CONSORT (consolidated standards of reporting trials) statement and the 2008 CONSORT extension for trials assessing non-pharmacologic treatments to describe and compare the underlying rationale, commonalities, and differences. All three trials conform to CONSORT guidelines, address the same fundamental questions, and share key design elements. Each trial is a patient-level, equal-randomized, parallel-group superiority trial that seeks to enroll emergency department patients with inclusion criteria that are consistent with the original early goal-directed therapy (EGDT) trial (suspected or confirmed infection, two or more systemic inflammatory response syndrome criteria, and refractory hypotension or elevated lactate), is powered to detect a 6–8 % absolute mortality reduction (hospital or 90-day), and uses trained teams to deliver EGDT. Design differences appear to primarily be driven by between-country variation in health care context. The main difference between the trials is the inclusion of a third, alternative resuscitation strategy arm in ProCESS. Harmonization of study design and methods between severe sepsis trials is feasible and may facilitate pooling of data on completion of the trials.


Analysis of female reproductive traits in Angus beef cattle divergently selected for blood serum insulin-like growth factor I concentration.
Insulin-like growth factor-I (IGF-I) is an anabolic polypeptide involved in reproductive performance in several species. The objectives of this study were to determine relationships of pregnancy rate, and age of heifers at puberty and at first calving with serum IGF-I concentration in Angus beef cattle. Data were obtained from an ongoing divergent selection experiment for IGF-I concentration involving purebred Angus cows. The IGF-I concentrations measured at Days 28, 42, and 56 of the 140-day postweaning test are abbreviated as IGF28, IGF42, and IGF56, respectively. Pregnancy rate did not differ between high and low IGF-I line females (P=0.95; n=2618), but high line heifers tended to be 4.02+/-2.18 days younger (P=0.07; n=281) at first calving. Residual correlations of age of heifers at first calving (AFC) with IGF-I measurements were not significant. The linear and quadratic terms for regression of AFC on IGF-I concentrations were also non-significant. Contrast analysis showed no difference in age at puberty between the high and low IGF-I line heifers (5.3+/-6.4 days earlier in the high line; P=0.43; n=51). Residual correlations of age of heifers at puberty with IGF28, IGF42, IGF56, and mean IGF-I were -0.30 (P=0.03), -0. 22 (P=0.12), -0.35 (P=0.01), and -0.34 (P=0.01), respectively. The observed relationships between female reproductive traits and IGF-I concentration in Angus beef cattle suggest complex and multiple roles for IGF-I in reproduction.


Tyrosine phosphorylation on spleen tyrosine kinase (Syk) is differentially regulated in human and murine platelets by protein kinase C isoforms.
Protein kinase C (PKC) isoforms differentially regulate platelet functional responses downstream of glycoprotein VI (GPVI) signaling, but the role of PKCs regulating upstream effectors such as Syk is not known. We investigated the role of PKC on Syk tyrosine phosphorylation using the pan-PKC inhibitor GF109203X (GFX). GPVI-mediated phosphorylation on Syk Tyr-323, Tyr-352, and Tyr-525/526 was rapidly dephosphorylated, but GFX treatment inhibited this dephosphorylation on Tyr-525/526 in human platelets but not in wild type murine platelets. GFX treatment did not affect tyrosine phosphorylation on FcRγ chain or Src family kinases. Phosphorylation of Lat Tyr-191 and PLCγ2 Tyr-759 was also increased upon treatment with GFX. We evaluated whether secreted ADP is required for such dephosphorylation. Exogenous addition of ADP to GFX-treated platelets did not affect tyrosine phosphorylation on Syk. FcγRIIA- or CLEC-2-mediated Syk tyrosine phosphorylation was also potentiated with GFX in human platelets. Because potentiation of Syk phosphorylation is not observed in murine platelets, PKC-deficient mice cannot be used to identify the PKC isoform regulating Syk phosphorylation. We therefore used selective inhibitors of PKC isoforms. Only PKCβ inhibition resulted in Syk hyperphosphorylation similar to that in platelets treated with GFX. This result indicates that PKCβ is the isoform responsible for Syk negative regulation in human platelets. In conclusion, we have elucidated a novel pathway of Syk regulation by PKCβ in human platelets.


Megacystis-microcolon-intestinal hypoperistalsis syndrome associated with cystic fibrosis and meconium peritonitis in a female neonate 4 days of age - case report and review of the literature.
We present a case of megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) in a four days old female infant who presented with abdominal distension, bilious vomiting, massive hematuria and feeding intolerance which was first interpreted as Prune Belly Syndrome (PBS), referred to our department after iatrogenic gastric and colonic perforation. Berdon syndrome or MMIHS is a rare congenital anomaly characterized by a massive enlarged bladder, distended abdomen, microcolon, functional obstruction of the gastrointestinal tract, and malrotation.


The Hitchhiker's guide to longitudinal models: A primer on model selection for repeated-measures methods.
Longitudinal data are becoming increasingly available in developmental neuroimaging. To maximize the promise of this wealth of information on how biology, behavior, and cognition change over time, there is a need to incorporate broad and rigorous training in longitudinal methods into the repertoire of developmental neuroscientists. Fortunately, these models have an incredibly rich tradition in the broader developmental sciences that we can draw from. Here, we provide a primer on longitudinal models, written in a beginner-friendly (and slightly irreverent) manner, with a particular focus on selecting among different modeling frameworks (e.g., multilevel versus latent curve models) to build the theoretical model of development a researcher wishes to test. Our aims are three-fold: (1) lay out a heuristic framework for longitudinal model selection, (2) build a repository of references that ground each model in its tradition of methodological development and practical implementation with a focus on connecting researchers to resources outside traditional neuroimaging journals, and (3) provide practical resources in the form of a codebook companion demonstrating how to fit these models. These resources together aim to enhance training for the next generation of developmental neuroscientists by providing a solid foundation for future forays into advanced modeling applications.


Polydopamine-assisted grafting of chitosan on porous poly (L-lactic acid) electrospun membranes for adsorption of heavy metal ions.
In this study, a versatile method for the manufacturing of chitosan-grafted porous poly (L-lactic acid) (P-PLLA) nanofibrous membrane by using polydopamine (PDA) as an intermediate layer has been developed. P-PLLA fibres were electrospun and collected as nano/micro fibrous membranes. Highly porous fibres could serve as a substrate for chitosan to adsorb heavy metal ions. Moreover, PDA was used to modify P-PLLA surface to increase the coating uniformity and stability of chitosan. Due to the very high surface area of P-PLLA membranes and abundant amine groups of both PDA and chitosan, the fabricated membranes were utilized as adsorbent for removal of copper (Cu2+) ions from the wastewater. The adsorption capability of Cu2+ ions was examined with respect to the PDA polymerization times, pH, initial metal ion concentration and time. Finally, the equilibrium adsorption data of chitosan-grafted membranes fitted well with the Langmuir isotherm with the maximum adsorption capacity of 270.27 mg/g.


Medical students' change in learning styles during the course of the undergraduate program: from 'thinking and watching' to 'thinking and doing'.
Most students admitted to medical school are abstract-passive learners. However, as they progress through the program, active learning and concrete interpersonal interactions become crucial for the acquisition of professional competencies. The purpose of this study was to determine if and how medical students' learning styles change during the course of their undergraduate program. All students admitted to the Pontificia Universidad Católica de Chile (PUC) medical school between 2000 and 2011 (n = 1,290) took the Kolb's Learning Style Inventory at school entrance. Two years later 627 students took it again, and in the seventh and last year of the program 104 students took it for a third time. The distribution of styles at years 1, 3 and 7, and the mobility of students between styles were analyzed with Bayesian models. Most freshmen (54%) were classified as assimilators (abstract-passive learners); convergers (abstract-active) followed with 26%, whereas divergers (concrete-passive) and accommodators (concrete-active) accounted for 11% and 9%, respectively. By year 3, the styles' distribution remained unchanged but in year 7 convergers outnumbered assimilators (49% vs. 33%). In general, there were no gender-related differences. Medical students change their preferred way of learning: they evolve from an abstract-reflexive style to an abstract-active one. This change might represent an adaptation to the curriculum, which evolves from a lecture-based teacher-centered to a problem-based student-centered model.


[Patient-reported outcomes and quality of care in specialized palliative home care: a nationwide, prospective longitudinal cohort trial].
Since 2007, patients receiving palliative care have been entitled to specialised outpatient palliative care (SAPV). Until now, the quality of care of the SAPV was only regionally focussed or in relation to individual SAPV teams. A nationwide analysis of outcome quality is still awaited. The organisation and design of structures and processes vary greatly from region to region, which complicates a comparative assessment of implementation. One way to measure the quality of the heterogeneous structures and processes is to collect patient-reported outcomes. Here, it is possible to use symptom burden, quality of care and patient satisfaction with SAPV care, since patients' quality of life is a central focus of SAPV care. This article is part of the research project SAVOIR, which is funded by the G-BA Innovation Fund. For this prospective longitudinal survey of the outcome quality of SAPV, structured data were collected at two measurement points (t1 and t2 [4-10 days after t1]). A nationwide, representative sample of SAPV teams was targeted. These teams performed consecutive recruitment of patients included in SAPV. Two questionnaire instruments were used: the IPOS (Integrated Palliative Outcome Scale) at t1 and t2, and the QUAPS (quality control in specialized palliative home care) questionnaire at t2. Patient-reported outcomes measured improvement in symptom burden, patient satisfaction, and quality of care from the patient perspective. In addition, an exploratory stepwise regression analysis of factors associated with satisfaction was conducted. 42 SAPV teams agreed to participate in the study. They recruited a total of 964 patients at measurement time t1 (t2: 690 patients). The analyses show that the number and intensity of symptoms from the patient perspective decreased significantly during the course of SAPV treatment, especially pain, gastrointestinal symptoms, but also psychological complaints. 74.7 % of the patients reported a high level of satisfaction with SAPV. Also, the quality of care was considered to be high by the patients. Exploratively, five factors were extracted that explain 55 % of the satisfaction with SAPV: respect for the patient's decision, quality of communication, support with practical problems, and referral to care measures as well as symptom relief between the two measurement points. The SAPV patients recruited from a total of nine KV regions reported a reduced symptom burden and a high level of satisfaction with SAPV and rated the quality of care provided by SAPV as high.


Interactive effect of cytochrome P450 17alpha-hydroxylase and dopamine D3 receptor gene polymorphisms on abnormal involuntary movements in chronic schizophrenia.
Tardive dyskinesia is a chronic adverse effect of anti psychotic drugs, where association with a polymorphic site in the dopamine D3 receptor gene has been previously reported. Cytochrome P 450 17alpha-hydroxylase activity has been implicated with modulation of central dopamine release as well as neuroprotection. We investigated the association of a T -->C variation in the cytochrome P 450 17alpha-hydroxylase gene with tardive dyskinesia in patients with chronic schizophrenia. Cytochrome P 450 17 allele and genotype frequencies were compared between matched schizophrenia patients with (n = 55) or without tardive dyskinesia (n = 58). Interactive effects of cytochrome P 450 17alpha-hydroxylase with the dopamine D3 Ser9Gly polymorphism on abnormal involuntary movements were examined. There was no difference in cytochrome P 450 17alpha-hydroxylase genotype distribution between patients with and without tardive dyskinesia; however, patients carrying the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype and the dopamine D3gly allele had the highest orofacial (p <.04), distal (p <.05), and incapacitation (p <.04) scores on the Abnormal Involuntary Movements Scale. Schizophrenia patients who carry the dopamine D3gly allele and the cytochrome P 450 17alpha-hydroxylase A2-A2 genotype may be more likely to develop abnormal orofoacial and distal involuntary movements and to be incapacitated by these movements when chronically exposed to classical antipsychotic drugs.


Predictive Markers of First Line Pazopanib Treatment in Kidney Cancer.
Real-world evidence from clinical practices is fundamental for understanding the efficacy and tolerability of medicinal products. Patients with renal cell cancer were studied to gain data not represented by analyses conducted on highly selected patients participating in clinical trials. Our goal was to retrospectively collect data from patients with advanced renal tumours treated with pazopanib (PZ) to investigate the efficacy, frequency of side effects, and searching for predictive markers. Eighty-one patients who had received PZ therapy as first-line treatment were retrospectively evaluated. Overall survival (OS), progression-free survival (PFS) were assessed as endpoints. Median PFS and OS were 11.8 months (95% CI: 8.8-22.4); and 30.2 months (95% CI: 20.3-41.7) respectively. Severe side effects were only encountered in 11 (14%) patients. The presence of liver metastasis shortened the median PFS (5.5 vs. 14.8 months, p = 0.003). Median PFS for patients with or without side effects was 25.6 vs. 7.3 months, respectively (p = 0.0001). Patients younger than 65 years had a median OS of 41.7 months vs. 25.2 months for those over 65 years of age (p = 0.008). According to our results absence of liver metastases, younger age (<65 years) and presence of side effects proved to be independent predictive markers of better PFS and OS.


Up-regulation of COX-2 by inhibition of COX-1 in the rat: a key to NSAID-induced gastric injury.
A recent study demonstrated that inhibition of both cyclooxygenase (COX)-1 and COX-2 is required for the development of nonsteroidal anti-inflammatory drug (NSAID)-induced gastric lesions. However, the role of COX-1 or COX-2 inhibition in the pathogenisis of these lesions remains unclear. To examine the gastric ulcerogenic properties of selective COX-1 and COX-2 inhibitors in rats and to investigate further the relationship of COX inhibition to various events involved in the process of NSAID-induced gastric lesions. Animals were given various COX inhibitors p.o., either alone or in combination, and killed 8 h later. Under the treatment, gastric damage, prostaglandin (PG) E2 content, mucosal permeability, myeloperoxidase (MPO) activity as well as gastric motility were examined. The nonselective COX inhibitor indomethacin inhibited PGE2 production, enhanced gastric motility, and provoked severe lesions in the stomach, with an increase in mucosal permeability and MPO activity. In contrast, the selective COX-2 inhibitor rofecoxib did not induce any damage in the stomach and had no effect on mucosal PGE2 content. Similarly, the selective COX-1 inhibitor SC-560 also caused no gastric damage, despite inhibiting PGE2 production. The combined administration of SC-560 and rofecoxib, however, provoked gross damage in the gastric mucosa, in a dose-dependent manner for each drug. SC-560, but not rofecoxib, caused marked gastric hypermotility and an increase in mucosal permeability, although an increase in MPO activity was observed only when rofecoxib was coadministered. The normal gastric mucosa expressed COX-1 mRNA and not COX-2 mRNA, but COX-2 mRNA was expressed in the stomach after administration of SC-560 as well as indomethacin but not rofecoxib. These results suggest that the gastric ulcerogenic properties of NSAIDs are not accounted for solely by COX-1 inhibition, but require the inhibition of both COX-1 and COX-2. The inhibition of COX-1 up- regulates COX-2 expression, and COX-2/PGs may, in turn, counteract the deleterious affects of gastric hypermotility due to COX-1 inhibition.


Targeting pyroptosis as a preventive and therapeutic approach for stroke.
Stroke has caused tremendous social stress worldwide, yet despite decades of research and development of new stroke drugs, most have failed and rt-PA (Recombinant tissue plasminogen activator) is still the accepted treatment for ischemic stroke. the complexity of the stroke mechanism has led to unsatisfactory efficacy of most drugs in clinical trials, indicating that there are still many gaps in our understanding of stroke. Pyroptosis is a programmed cell death (PCD) with inflammatory properties and are thought to be closely associated with stroke. Pyroptosis is regulated by the GSDMD of the gasdermin family, which when cleaved by Caspase-1/Caspase-11 into N-GSDMD with pore-forming activity can bind to the plasma membrane to form small 10-20 nm pores, which would allow the release of inflammatory factors IL-18 and IL-1β before cell rupture, greatly exacerbating the inflammatory response. The pyroptosis occurs mainly in the border zone of cerebral infarction, and glial cells, neuronal cells and brain microvascular endothelial cells (BMECs) all undergo pyroptosis after stroke, which largely exacerbates the breakdown of the blood-brain barrier (BBB) and thus aggravates brain injury. Therefore, pyroptosis may be a good direction for the treatment of stroke. In this review, we focus on the latest mechanisms of action of pyroptosis and the process by which pyroptosis regulates stroke development. We also suggest potential therapeutic stroke drugs that target the pyroptosis pathway, providing additional therapeutic strategies for the clinical management of stroke. The role of pyroptosis after stroke. After stroke, microglia first rush to the damaged area and polarize into M1 and M2 types. Under the influence of various stimuli, microglia undergo pyroptosis, release pro-inflammatory factors, and are converted to the M1 type; astrocytes and neuronal cells also undergo pyroptosis under the stimulation of various pro-inflammatory factors, leading to astrocyte death due to increased osmotic pressure in the membrane, resulting in water absorption and swelling until rupture. BMECs, the main structural component of the BBB, also undergo pyroptosis when stimulated by pro-inflammatory factors released from microglia and astrocytes, leading to the destruction of the structural integrity of the BBB, ultimately causing more severe brain damage. In addition, GSDMD in neutrophils mainly mediate the release of NETs rather than pyroptosis, which also aggravates brain injury. IL-10=interleukin-10; TGF-β = transforming growth factor-β; IL-18=interleukin-18; IL-1β = interleukin-1β; TNF-α = tumor necrosis factor-α; iNOS=induced nitrogen monoxide synthase; MMPs=Matrix metalloproteinases; GSDMD = gasdermin D; BMECs=brain microvascular endothelial cells; BBB = blood-brain barrier.


Phase I clinical trial of 1-(2-[2-(4-pyridyl)-2-imidazoline-1-yl]-ethyl)-3-(4-carboxy-phenyl) urea (CGP 15720A).
A phase I clinical trial of the intravenous administration of a novel pyridyl imidazoline ethyl carboxy phenyl urea was carried out in 42 patients with advanced solid tumors. Five schedules were evaluated: I, daily X 5; II, daily X 10; III, daily X 15; IV, continuous infusion for 5 days; V, continuous infusion for 7 days. Toxicity was not seen in schedule I (maximum dose 3 g/m2/day) and was minimal in schedule IV (6 g/m2/day). In schedule II it was seen at 2 and 3 g/m2/day, in schedule III at 2 g/m2/day and in schedule V at 6 g/m2/day. Dose-limiting toxicity consisted of a syndrome of lethargy and fatigue. There were no definitely drug-related changes in hematologic or serum chemistry parameters. No responses were seen, but relief of pain in three patients with prostate cancer was noted. Pharmacokinetics indicate a short half-life, limited volume of distribution, and rapid renal clearance. The recommended dose for phase II studies is 3 g/m2/day X 10 or 2 g/m2/day X 15 days.


Peracetic acid for conditioning of municipal wastewater sludge: Hygienization, odor control, and fertilizing properties.
Peracetic acid (PAA) is an environmentally friendly disinfectant and oxidizer used in several water and wastewater treatment applications. In the present study, PAA was utilized for the conditioning of municipal wastewater sludge before thickening and dewatering. It was shown that PAA can effectively prevent odor formation (i.e., H2S and NH3) and provide hygienization (using E. coli and Salmonella as indicators). Phytotoxicity can be prevented by controlling the amount PAA-conditioned sludge that is mixed in the soil to be fertilized. The required PAA dose for hygienization was relatively high (480 mg 100% PAA perL sludge) but the results indicated that other sludge stabilization processes are not necessarily required. Therefore, the proposed process involving PAA could be feasible in cases where limited land area is available for sludge processing or quick conditioning of sludge is required.


Shedding of viral hemorrhagic septicemia virus (Genotype IVb) by experimentally infected muskellunge (Esox masquinongy).
Previous experimental infection demonstrated that juvenile muskellunge (Esox masquinongy) can survive experimental infection of viral hemorrhagic septicemia virus, Genotype IVb (VHSV IVb) at a low concentration of exposure. Herein we report that survivors of experimental infection with VHSV IVb shed the virus into the surrounding environment for an extended period of time. When muskellunge were exposed to VHSV IVb by immersion at a concentration of 1,400 plaque forming units (PFU)/ml, VHSV IVb was detected in the water of surviving fish for up to 15 weeks postexposure (p.e.) with the highest levels of shedding occurring between weeks 1 and 5 p.e. We estimated that each juvenile muskellunge can shed upwards of 1.36×10(5) PFU/fish/h after initial exposure signifying the uptake and amplification of VHSV to several orders of magnitude above the original exposure concentration. Muskellunge surviving low concentration exposure were re-infected with VHSV IVb by immersion at week 22 p.e. at concentrations ranging from 0 to 10(6) PFU/ml. Viral shedding was detected in all re-exposed fish, including mock rechallenged controls up to 15 consecutive weeks. Rates of viral shedding were substantially higher following rechallenge in the first 5 weeks. The highest rate of viral shedding was approximately 4.6×10(6) PFU/fish/h and shedding did not necessarily correspond to the re-exposure VHSV concentration. The results of this study shed new light into the dynamics of VHSV IVb shedding in a highly susceptible host and provide useful insights to fishery managers to design effective control strategies to this deadly virus.


[Analysis of clinical characteristics and risk factors of early heat stroke-related acute liver injury].
To analyze the clinical characteristics and risk factors of early acute liver injury in patients with heat stroke (HS), and to provide basis for early identification of HS-related liver injury and its pathogenesis in clinical practice. The clinical data of patients with HS admitted to the department of critical care medicine of Haian People's Hospital from June 2015 to August 2022 were retrospectively analyzed. The patients with HS were divided into early liver injury group and early non-liver injury group according to the occurrence of acute liver injury within 24 hours of admission. The differences of basic data, clinical data, laboratory indexes and clinical outcomes of the two groups were analyzed. Logistic regression was used to analyze the risk factors for early HS-related acute liver injury, and receiver operator characteristic (ROC) curves were drawn to evaluate their value in predicting the occurrence of early HS-related acute liver injury. A total of 76 patients with HS were enrolled, and 46 patients with acute liver injury, accounting for 60.53%. In the early liver injury group, 14 patients (30.43%) had elevated aminotransferase alone, 9 patients (19.57%) had elevated total bilirubin (TBil) alone, and 23 patients (50.00%) had elevated both aminotransferase and TBil. Among the patients with elevated aminotransferases, 24 patients (64.87%) had mild elevation, 5 patients (13.51%) had moderate elevation, 8 patients (21.62%) had severe elevation. Compared with the early non-liver injury group, acute physiology and chronic health evaluation II (APACHE II), sequential organ failure assessment (SOFA), arterial blood lactate (Lac), interleukin-6 (IL-6), procalcitonin (PCT), alanine aminotransferase (ALT), aspartate aminotransferase (AST), TBil, γ-gamma glutamyl transferase (γ-GGT), lactate dehydrogenase (LDH), creatine kinase (CK), MB isoenzyme of creatine kinase (CK-MB), cardiac troponin I (cTnI), myoglobin (MYO), N-terminal B-type pro-brain natriuretic peptide (NT-proBNP), prothrombin time (PT), activated partial thromboplastin time (APTT), D-dimer in the early liver injury group were significantly increased, while platelet count (PLT) were significantly decreased within 24 hours after admission, the 28-day mortality was significantly increased [28.26% (13/46) vs. 6.67% (2/30)], and the differences were statistically significant (all P < 0.05). Univariate Logistic regression analysis showed that APACHE II score, SOFA score, PLT, Lac, IL-6, PCT, γ-GGT, LDH, CK, CK-MB, cTnI, MYO, PT, APTT, D-dimer were risk factors of early HS-related acute liver injury (all P < 0.05). Multivariate Logistic regression analysis showed that PLT, IL-6, and LDH were independent risk factors of early HS-related acute liver injury [odds ratio (OR) and 95% confidence interval (95%CI) were 0.986 (0.974-0.998), 1.027 (1.012-1.041), and 1.002 (1.000-1.004), all P < 0.05]. The ROC curve analysis showed that the area under the ROC curve (AUC) of PLT, IL-6 and LDH for predicting the occurrence of early HS-related acute liver injury was 0.672 (95%CI was 0.548-0.797), 0.897 (95%CI was 0.824-0.971) and 0.833 (95%CI was 0.739-0.927), respectively. IL-6 had the highest predictive value for early HS-related liver injury. When the optimal diagnostic threshold of IL-6 was 48.25 ng/L, the sensitivity was 95.7%, the specificity was 73.3%, and the predictive value of PLT was the lowest. The early HS-related liver injury is mainly manifested as the simultaneous elevation of aminotransferase and TBil, and most of cases are mild liver injury. PLT, IL-6 and LDH are independent risk factors of early HS-related acute liver injury.


Dairy product purchasing in households with and without children.
Dairy products are considered a staple in the American diet due in part to their nutritious content and appealing flavor. Consumption patterns may differ among age segments influenced by preferences for fat content and taste in dairy. Furthermore, having children in their household may influence the amount, frequency, and type of dairy products that a consumer chooses to purchase. This study finds that households that frequently bought food for children generally purchased larger quantities of fluid milk and more fluid milk with a higher fat content. Households with children also bought yogurt more frequently than other households. Labeling information of interest to the largest proportion of respondents was price; unsurprisingly, expiration date was second most common on meat, eggs, or milk product packaging. Although the scientific and cultural debate of the benefit or harm of consuming dairy continues, it is clear that the segment of the population that frequently purchases food for children is interested in dairy as part of the diet of the children. It would be interesting to see whether this finding has a spillover effect on the consumption habits of adults making the purchases. Future studies can build on this work by evaluating whether there is a spillover effect from purchasing specifically for children and the general dairy and protein product purchasing habits of those households.


Absence of correlation between magnesium and riboflavin status.
Erythrocyte magnesium and glutathione reductase activity coefficient (EGR-AC), reflecting vitamin B-2 status, were assessed in 11 athletes, 20 patients with fibromyalgia, 18 patients with hypothyroidism, and 13 controls. No correlation was demonstrated between erythrocyte magnesium and EGR-AC.


Characterization of dysregulated glutamine metabolism in human glioma tissue with 1H NMR.
Gliomas are one of the most common types of brain tumors. Given low survival and high treatment resistance rates, particularly for high grade gliomas, there is a need for specific biomarkers that can be used to stratify patients for therapy and monitor treatment response. Recent work has demonstrated that metabolic reprogramming, often mediated by inflammation, can lead to an upregulation of glutamine as an energy source for cancer cells. As a result, glutamine pathways are an emerging pharmacologic target. The goal of this pilot study was to characterize changes in glutamine metabolism and inflammation in human glioma samples and explore the use of glutamine as a potential biomarker. 1H high-resolution magic angle spinning nuclear magnetic resonance spectra were acquired from ex vivo glioma tissue (n = 16, grades II-IV) to quantify metabolite concentrations. Tumor inflammatory markers were quantified using electrochemiluminescence assays. Glutamate, glutathione, lactate, and alanine, as well as interleukin (IL)-1β and IL-8, increased significantly in samples from grade IV gliomas compared to grades II and III (p ≤ .05). Following dimension reduction of the inflammatory markers using probabilistic principal component analysis, we observed that glutamine, alanine, glutathione, and lactate were positively associated with the first inflammatory marker principal component. Our findings support the hypothesis that glutamine may be a key marker for glioma progression and indicate that inflammation is associated with changes in glutamine metabolism. These results motivate further in vivo investigation of glutamine as a biomarker for tumor progression and treatment response.


[Electrical safety of endoscopic equipment].
The article considers in detail the problems affecting the safety of the patients and the medical personnel during endoscopic examinations, gives practical recommendations both to the endoscope makers and users.


Outcomes of status 1 liver transplantation for Budd-Chiari Syndrome with fulminant hepatic failure.
There is a paucity of data on the outcome of liver transplantation (LT) in Budd-Chiari Syndrome (BCS) patients who are listed as status 1. The objective of our study was to determine patient or graft survival following LT in status 1 BCS patients. We utilized United Network for Organ Sharing (UNOS) database to identify all adult patients (> 18 years of age) listed as status 1 with a primary diagnosis of BCS in the United States from 1998 to 2018, and analyzed their outcomes and compared it to non-status 1 BCS patients. Four hundred and forty-six patients with BCS underwent LT between 1998 and 2018, and of these 55 (12.3%) were listed as status 1. There was no difference in long-term post-liver transplant or "intention-to-treat" survival from the time of listing to death or the last day of follow-up between status 1 and non-status 1 groups. Graft and patient survival at 5 years for status 1 patients were 75% and 82%, respectively. Cox regression analysis showed that patients listed as status 1 (aHR: 0.45, p < .02) were associated with a better survival. BCS patients listed as status 1 have excellent survival following emergency LT.


Brodie's abscess--an uncommon cause of leg pain.
A rare case of Brodie's abscess of distal left tibia is presented in a child which was initially missed on clinical grounds alone. Differentiation from different bone neoplasms was done on radiological grounds. The patient was managed surgically with high dose intravenous antibiotics. Brodie's abscess is very rarely encountered in our reporting of X-rays.


The nature and mechanism of superoxide production by the electron transport chain: Its relevance to aging.
Most biogerontologists agree that oxygen (and nitrogen) free radicals play a major role in the process of aging. The evidence strongly suggests that the electron transport chain, located in the inner mitochondrial membrane, is the major source of reactive oxygen species in animal cells. It has been reported that there exists an inverse correlation between the rate of superoxide/hydrogen peroxide production by mitochondria and the maximum longevity of mammalian species. However, no correlation or most frequently an inverse correlation exists between the amount of antioxidant enzymes and maximum longevity. Although overexpression of the antioxidant enzymes SOD1 and CAT (as well as SOD1 alone) have been successful at extending maximum lifespan in Drosophila, this has not been the case in mice. Several labs have overexpressed SOD1 and failed to see a positive effect on longevity. An explanation for this failure is that there is some level of superoxide damage that is not preventable by SOD, such as that initiated by the hydroperoxyl radical inside the lipid bilayer, and that accumulation of this damage is responsible for aging. I therefore suggest an alternative approach to testing the free radical theory of aging in mammals. Instead of trying to increase the amount of antioxidant enzymes, I suggest using molecular biology/transgenics to decrease the rate of superoxide production, which in the context of the free radical theory of aging would be expected to increase longevity. This paper aims to summarize what is known about the nature and mechanisms of superoxide production and what genes are involved in controlling the rate of superoxide production.


Ultrasonic treatment of foam for the prevention of foam-induced pepsin inactivation.
The phenomenon of foam-induced inactivation is a common challenge during foam fractionation of proteins. In this work, we attempted to use ultrasound to treat foam out of the foam fractionation column with the aim of minimizing the foam-induced protein inactivation using pepsin as a model protein. Firstly, the mechanisms by which ultrasound prevented the foam-induced pepsin inactivation during defoaming were explored. The results showed that ultrasound promoted the refolding of unfolded pepsin molecules at the gas-liquid interface to restore their activities during the desorption process from the interface and before dissolving into the foamate. Subsequently, the effects of ultrasonic power on the pepsin renaturation were analyzed, which revealed that the unfolding degree of pepsin in the foamate gradually decreased and then increased as the ultrasonic power increased. Correspondingly, the specific activity of pepsin in the foamate increased and then decreased. Finally, we explored the effects of defoaming efficiency, type of gas and pH. The results indicated that the decrease in defoaming efficiency and gas solubility in water facilitated the ultrasound-assisted pepsin renaturation in the pH range from 1.0 to 2.5. When air was applied in the foaming process, the specific activity of pepsin in the foamate with ultrasonic treatment was not significantly different from that in the feed solution at ultrasonic power of 400 W and pH 2.0. Collectively, these results indicate the ultrasonic treatment of foam effectively prevented the foam-induced pepsin inactivation.


Different histological manifestation of glomerular lesions in familial systemic lupus erythematosus.
Lupus nephritis in a sister and brother pair was histologically analyzed. The 12-year-old sister showed clinically progressive renal failure and her renal pathology disclosed segmental necrotizing and disorganizing glomerulonephritis. On the contrary, the 14-year-old brother exhibited nephrotic syndrome and his renal biopsy showed diffuse exudative and proliferative glomerulonephritis with segmental membraneous changes. Although the familial incidence of SLE suggests both genetic and environmental factors existing in the background of SLE of identical twins and siblings, the differences of clinical manifestation and histopathological findings imply that there might be little direct genetic and environmental control on determining the expression of the disease.