Cross-cultural adaptation and psychometric evaluation of the Brazilian Portuguese version of the childbirth experience questionnaire.
The Childbirth Experience Questionnaire (CEQ) is a tool designed to assess women's perceptions about labor and delivery. The aim of this study was to perform the cross-cultural adaptation and validation of the Brazilian Portuguese version of the CEQ (CEQ-Br). The original version of the CEQ was translated into Portuguese, analyzed by a committee of experts, back translated, and finally submitted to pilot-test. Two applications of the CEQ-Br were performed along with the quality of life questionnaire Medical Outcomes Study 36 - Item Short-Form Health Survey (SF-36). The SPSS software was used for statistical analysis, the intraclass correlation coefficient was used to investigate test-retest reliability, the internal consistency was investigated with the Cronbach's Alpha, and the construct validity was investigated via the Spearman correlation test. The level of significance was set at 5%. The study included 308 women with a mean age of 31.1 ± 8.7 years. The internal consistency results for the total CEQ-Br score was considered adequate (0.89), the test-retest showed a substantial result with an ICC of 0.90, and the construct validity was analyzed via the Spearman correlation between all SF-36 dimensions and the total CEQ-B score, the analyses were considered adequate. The results presented in this CEQ-Br validation study showed that the instrument was reliable in measuring the established psychometric properties and was considered valid. Therefore, the CEQ-Br can be applied to the Brazilian population.


Frog Virus 3 dissemination in the brain of tadpoles, but not in adult Xenopus, involves blood brain barrier dysfunction.
While increasing evidence points to a key role of monocytes in amphibian host defenses, monocytes are also thought to be important in the dissemination and persistent infection caused by ranavirus. However, little is known about the fate of infected macrophages or if ranavirus exploits immune privileged organs, such as the brain, in order to establish a reservoir. The amphibian Xenopus laevis and Frog Virus 3 (FV3) were established as an experimental platform for investigating in vivo whether ranavirus could disseminate to the brain. Our data show that the FV3 infection alters the BBB integrity, possibly mediated by an inflammatory response, which leads to viral dissemination into the central nervous system in X. laevis tadpole but not adult. Furthermore, our data suggest that the macrophages play a major role in viral dissemination by carrying the virus into the neural tissues.


Distinct and dynamic activation profiles of circulating dendritic cells and monocytes in mild COVID-19 and after yellow fever vaccination.
Dysregulation of the myeloid cell compartment is a feature of severe disease in hospitalized COVID-19 patients. Here, we investigated the response of circulating dendritic cell (DC) and monocyte subpopulations in SARS-CoV-2 infected outpatients with mild disease and compared it to the response of healthy individuals to yellow fever vaccine virus YF17D as a model of a well-coordinated response to viral infection. In SARS-CoV-2-infected outpatients circulating DCs were persistently reduced for several weeks whereas after YF17D vaccination DC numbers were decreased temporarily and rapidly replenished by increased proliferation until 14 days after vaccination. The majority of COVID-19 outpatients showed high expression of CD86 and PD-L1 in monocytes and DCs early on, resembling the dynamic after YF17D vaccination. In a subgroup of patients, low CD86 and high PD-L1 expression were detected in monocytes and DCs coinciding with symptoms, higher age, and lower lymphocyte counts. This phenotype was similar to that observed in severely ill COVID-19 patients, but less pronounced. Thus, prolonged reduction and dysregulated activation of blood DCs and monocytes were seen in a subgroup of symptomatic non-hospitalized COVID-19 patients while a transient coordinated activation was characteristic for the majority of patients with mild COVID-19 and the response to YF17D vaccination.


Short-term administration of the GLP-1 analog liraglutide decreases circulating leptin and increases GIP levels and these changes are associated with alterations in CNS responses to food cues: A randomized, placebo-controlled, crossover study.
GLP-1 agonists, including liraglutide, have emerged as effective therapies for type 2 diabetes (DM) and obesity. Here, we attempted to delineate how liraglutide, at doses approved for DM, may impact circulating hormones influencing energy homeostasis in diabetics. Using a randomized, placebo-controlled, double-blind, cross-over trial of 20 patients with type 2 diabetes, we examined the effects of liraglutide as compared to placebo on fasting levels of circulating hormones important to energy homeostasis, including leptin, ghrelin, PYY, and GIP. After 17days (0.6mg for 7days, 1.2mg for 7days and 1.8mg for 3days) of treatment, we also studied changes in fMRI responses to food cues. By design, to avoid any confounding by weight changes, subjects were studied for 17days, i.e. before body weight changed. Participants on liraglutide had significantly increased GLP-1 levels (p<0.001), decreased percent change in leptin levels (p<0.01) and increased GIP levels (p<0.03) in comparison to placebo treated subjects. Whole brain regressions of functional activity in response to food cues reveal that increased GIP levels were associated with deactivation of the attention- and reward-related insula. Decreases in leptin levels were associated with activations in the reward-related midbrain, precuneus, and dorsolateral prefrontal cortex (DLPFC), and sensorimotor-related motor cortex and with deactivations in the attention-related parietal cortex and the cognitive control-related thalamus and pre-SMA. We demonstrate herein short-term changes to circulating levels of GIP and leptin in response to GLP-1 agonist liraglutide therapy. These findings suggest that liraglutide may alter the circulating levels of hormones important in energy homeostasis that, in turn, influence CNS perception of food cues. This could possibly lead to compensatory changes in energy homeostasis that could over time limit the efficacy of liraglutide to decrease body weight. These novel findings, which, pointing to the potential advantages of combination therapies, may have therapeutic implications, will need to be confirmed by larger and longer-term trials.


An analysis of local government health policy against state priorities and a social determinants framework.
Victorian local governments are required to develop Municipal Public Health and Wellbeing Plans that incorporate state-level health planning priorities and address the social determinants of health. This paper describes a novel method for evaluating councils' performance against these requirements. Deductive content analysis was used to categorise all actions in 14 local government MPHWPs against Victorian state priorities as well as against social determinants of health policy areas. More than 1,000 actions were identified. However, fewer than half directly addressed a state priority, with many actions addressing policy areas known to be broader determinants of health. In particular, there was a marked focus on leisure and culture, and on building social cohesion through changes to living and working conditions. Councils are working beyond state priorities and there was a clear emphasis on addressing the diverse upstream 'causes of the causes' of health, rather than health promotion behaviour change programs. The approach for data analysis and presentation provides a useful method for rapid appraisal of health and wellbeing actions relative to councils', and the State's, responsibility and efficacy in public health.


Immunophenotypic challenges in diagnosis of CD79a negativity in a patient with B acute lymphoblastic leukemia harboring intrachromosomal amplification of chromosome 21: a case report.
Being expressed in all stages of B-cell development and having a significant value on the European Group for the Immunological Characterization of Acute Leukemias scoring system, CD79a is considered as an excellent pan-marker for lineage assignment of B cells by flow cytometry. Therefore, any lack or decrease in CD79a expression makes the diagnosis of B acute lymphoblastic leukemia cases very challenging, especially in developing country laboratories where flow cytometry analyses are not always available and, when they are, they are limited in the number of markers used for lineage assignment. Since this case is potentially interesting, we report a B acute lymphoblastic leukemia case with a lack of expression CD79a associated with intrachromosomal amplification of chromosome 21 genetic abnormality. We further discuss the practical challenges in the diagnosis of this case. We present the case of an 8-year-old Caucasian boy from eastern Morocco who was initially hospitalized for a hemorrhagic syndrome. Peripheral blood smear examination showed a significant number of blasts suggesting acute leukemia. Bone marrow was studied for morphology, cytochemistry, immunophenotyping, and cytogenetics. Flow cytometry analyses showed expression of CD19, CD22, CD10, CD34, and HLA-DR markers by leukemic blasts. The expression of CD79a, which was checked with two different monoclonal antibodies, confirms that this marker was severely decreased in this case. Cytogenetic study performed by fluorescence in situ hybridization revealed the presence of intrachromosomal amplification of chromosome 21, a cytogenetic abnormality that is specific for B acute lymphoblastic leukemia. CD79a is one of the critical markers in the assignment of B acute lymphoblastic leukemia. In our case, we were lucky enough to be assisted by a few other markers of the B lineage that were positive in this case. Also, we mention the importance of proceeding to cytogenetic study, which in our case helped us to confirm the diagnosis made by flow cytometry by highlighting a cytogenetic abnormality that is specific to B acute lymphoblastic leukemia.


Binding studies for serotoninergic, dopaminergic and noradrenergic receptors of Valeriana adscendens Trel. extracts.
Valeriana adscendens Trel. (Valerianaceae) is a psychoactive plant usually used in magical-therapeutic rituals in traditional practices of the Northern Peruvian Andes. Previous studies have been carried out on extracts of aerial parts in order to validate its traditional use. The results indicated that Valeriana adscendens exerts important effects on the central nervous system. Aim of the present study is to evaluate if the effects on the central nervous system of Valeriana adscendens extracts can be associated with interaction with some CNS receptors. In this work we examined affinity and selectivity of two Valeriana adscendens extracts (methanolic and aqueous) towards 5-HT(1A), 5-HT(2A), 5-HT(2C) serotononergic, D(1) and D(2) dopaminergic, alpha(1) and alpha(2) noradrenergic receptors by a preliminary binding screen. The results show weak affinity to 5-HT(1A) for the aqueous extract. Both extracts showed affinity for D(1) receptors, but only for the methanolic extract the IC(50) value was determinable (30.14 microg/ml). No affinity for 5-HT(2A), 5-HT(2C) serotononergic receptors, alpha(1) and alpha(2) noradrenergic receptors and D(2) receptors was recorded for the extracts.


Miracles and the limits of medical knowledge.
In considering whether medical miracles occur, the limits of epistemology bring us to confront our metaphysical worldview of medicine and nature in general. This raises epistemological questions of a higher order. David Hume's understanding of miracles as violations of the laws of nature assumes that nature is completely regular, whereas doctrines such as C. S. Peirce's "tychism" hold that there is an element of absolute chance in the workings of the universe. Process philosophy gives yet another view of the working of nature. Physicians have no epistemological grounds for declaring any cure to be miraculous. Miracles are theological (or philosophical) entities, and not medical entities. All physicians can do is to determine whether or not a cure is scientifically inexplicable according to the current epistemological standards of medical science. As these standards change, what is currently unexplainable may become explainable. However, we can also come to realize that our current explanations are in fact unsatisfactory. Our justifications of knowledge claims about miracles will depend on our views about determinism and indeterminism. If the universe is not a deterministic one, we should be open to the possibility of encountering what appear to us as sui generis events. These would not be violations of immutable laws of nature, but manifestations of the true workings of nature, and certainly causes for wonder.


Effect of the functional toll-like receptor 4 Asp299Gly polymorphism on susceptibility to late-onset Alzheimer's disease.
Experimental data have shown an upregulated expression of toll-like receptors, particularly toll-like receptor 4 (TLR4), in neurodegeneration. The Asp299Gly polymorphism of the TLR4 gene has been associated with an attenuated receptor signalling and a blunted inflammatory response. In the present study, we sought to determine whether this common genetic variant could influence susceptibility to late-onset Alzheimer's disease (LOAD) in an Italian population sample. A cohort of 277 LOAD patients and 300 cognitively healthy controls were genotyped for the TLR4 Asp299Gly polymorphism using restriction isotyping. The frequency of the minor 299Gly allele was significantly higher in the controls than in the LOAD cases (7.2% versus 3.1%, respectively, P=0.003). Additionally, the frequency of the variant genotypes (Asp/Gly and Gly/Gly) was 13.0% in the controls and 5.4% in LOAD patients (P=0.002). After adjustment for age, gender, and the APOE varepsilon4 carrier status, the odds ratio for the development of LOAD associated with the Asp/Gly and Gly/Gly versus Asp/Asp genotype was 0.37 (95% CI: 0.20-0.69, P=0.002). Our data further support a role for innate immunity in neurodegeneration and give the first evidence that the TLR4 Asp299Gly variant may be protective toward the development of LOAD.


Environmental control of rice flowering time.
Correct measurement of environmental parameters is fundamental for plant fitness and survival, as well as for timing developmental transitions, including the switch from vegetative to reproductive growth. Important parameters that affect flowering time include day length (photoperiod) and temperature. Their response pathways have been best described in Arabidopsis, which currently offers a detailed conceptual framework and serves as a comparison for other species. Rice, the focus of this review, also possesses a photoperiodic flowering pathway, but 150 million years of divergent evolution in very different environments have diversified its molecular architecture. The ambient temperature perception pathway is strongly intertwined with the photoperiod pathway and essentially converges on the same genes to modify flowering time. When observing network topologies, it is evident that the rice flowering network is centered on EARLY HEADING DATE 1, a rice-specific transcriptional regulator. Here, we summarize the most important features of the rice photoperiodic flowering network, with an emphasis on its uniqueness, and discuss its connections with hormonal, temperature perception, and stress pathways.


Determination of bisphenols in sewage based on supramolecular solid-phase extraction/liquid chromatography/fluorimetry.
Supramolecular sorbents (hemimicelles/admicelles) are proposed for the extraction/preconcentration of bisphenols from aqueous environmental samples prior to their liquid chromatography/fluorimetric determination. A comparative study on the use of cetyltrimethylammonium bromide (CTABr)-coated silica and sodium dodecyl sulphate (SDS)-coated gamma-alumina as sorbent materials, is presented. Bisphenol A (BPA) and bisphenol F (BPF) were quantitatively retained on CTABr admicelles. Addition of tetrabutylammonium chloride (TBAC) to water samples was required to completely retain bisphenols on SDS-gamma-alumina. Retention on both sorbents occurred through hydrophobic and pi-cation interactions between the quaternary ammonium head group of the cationic amphiphile (CTABr or TBAC) and the aromatic rings of the target analytes. TBAC-SDS-gamma-alumina was the sorbent selected for the SPE of bisphenols on the basis of the lower elution volume required (1 ml of methanol) and the greater breakthrough volume allowed (400 ml), which permitted to reach practical detection limits of 10 and 15 ng/l for BPF and BPA, respectively. The proposed method was used to quantify bisphenol A and bisphenol B in wastewater samples from four sewage treatment plants. Recoveries obtained ranged between about 99 and 105% for raw wastewater and between 96 and 106% for treated wastewater.


Conscious perception of bronchospasm as a protective phenomenon in asthma.
Ten initially asymptomatic asthmatic subjects underwent methacholine-induced attacks of asthma on a number of occasions, to the point when tightness in the chest was just sensed (threshold point). As baseline lung volumes increased and the caliber of the airways decreased, the relative changes needed to attain a threshold point generally became smaller. Although pulmonary function can deteriorate chronically without increasing dyspnea, it is possible that a mechanism exists at the level of consciousness to protect a subject's breathing at times when pulmonary function is acutely impaired.


A Systematic Approach to Evaluating Closed System Drug-Transfer Devices During Drug Product Development.
The use of Closed System Drug-Transfer Devices (CSTDs) has increased significantly in recent years due to NIOSH and USP recommendations to use them during preparation of hazardous drugs. Mechanistic and material differences between CSTDs and traditional in-use components warrant an assessment of their impact on product quality and dosing accuracy. Using a combination of prevalent CSTDs with biologic molecules, we performed an extensive assessment of the effect of using CSTDs for dose preparation and observed no negative impact on product quality attributes. Additionally, we found that the CSTD hold-up volume is 2 to 4-fold higher than conventional in-use components and exhibited a strong dependence on the CSTD brand used. We also found that the CSTD brand and dosing volume have a major influence on dosing accuracy with suboptimal protein recovery at very low dosing volumes. We identified entrapment of product in the CSTD spike as the root cause for this sub-optimal recovery and found that flushing the CSTD spike with a brand-new syringe and not the dosing syringe aided in complete protein recovery. Taken together we present a systematic approach to evaluate the risks and impact of CSTD to drug product quality, dose preparation, and dosing accuracy.


Resolution of the pathway taken by implanted Schwann cells to a spinal cord lesion by prior infection with a retrovirus encoding beta-galactosidase.
This series of experiments is designed to follow the fate of implanted Schwann cells by first labeling them with a recombinant retrovirus encoding the bacterial beta-galactosidase gene, then injecting them into the spinal cord after a demyelinating lesion has been produced. The label provides a means of distinguishing the exogenous Schwann cells from endogenous ones and of determining their travel pattern and myelinating or ensheathing behavior in the central nervous system (CNS). Neonatal rat primary Schwann cells were stimulated to divide by administering glial growth factor and forskolin. Fresh virus-containing supernatant from Psi2 cells producing retrovirus LZ1 was placed in cell culture to label the cells. The capacity of infected Schwann cells to form myelin was verified by coculturing in vitro with neurons from embryonic dorsal root ganglia. Infected cells were injected into the right side of adult syngenic rat spinal cords after a lysolecithin-induced demyelinating lesion had been produced 1 cm caudal on the left side. After 3 weeks the animals were killed, perfused for electron microscopy, and spinal cord sections histochemically stained for beta-galactosidase activity using the chromogenic substrate 5-bromo-4-chloro-3-indoyl-beta-D-galactosidase (X-Gal) which forms a blue precipitate in infected cells. The labeled cells, easily recognized macro- and microscopically, were clustered at the cell injection site, in the dorsal meninges and, at the area of demyelination, bilaterally in the superficial aspect of the dorsal funiculi. Labeled cells were not evident in the neuropil midway between the injection and demyelination sites.(ABSTRACT TRUNCATED AT 250 WORDS)


Effect of Lactobacillus rhamnosus GG on rBet v1 and rMal d1 specific IgA in the saliva of patients with birch pollen allergy.
Lactobacillus rhamnosus GG (LGG) has demonstrated promising results in the treatment and prevention of atopic eczema. To study the effects of LGG on the oral immune response in adolescents and adults with birch pollen allergy combined with oral allergy syndrome. Patients received either LGG (n = 19) or a placebo (n = 19) for 5.5 months (from February 8 to August 6, 1999), starting 2.5 months before the birch pollen season. An oral apple challenge test was performed before, during, and after the pollen season. Saliva samples were collected before and after the challenges, and serum samples were collected before the challenges. Total IgA, IgG, and IgM and rBet v1 and rMal dl specific IgA, IgG, IgG1, and IgG4 levels were measured from saliva with an enzyme-linked immunosorbent assay (ELISA). Serum rBet v1 specific IgE ELISA and birch radioallergosorbent testing were performed. After 5.5 months, rBet v1 and rMal dl specific IgA levels had increased from baseline in the LGG compared with the placebo group (delta rBet v1 IgA, 0.319 vs. -0.136 relative units; P = .02; delta rMal d1 IgA, 0.097 vs -0.117, P = .02). rBet v1 specific IgE serum levels did not differ between the groups. In the LGG group, rBet v1 specific IgE levels correlated positively with stimulated total IgA (P = .04) and IgG (P = .003) in saliva. In the placebo group, rBet vl specific IgE levels correlated negatively with stimulated rBet v1 and rMal d1 IgA levels (P = .009 for both) and IgG (P = .02 and P = .03, respectively). LGG showed immunostimulating effects on oral mucosa seen as increased allergen specific IgA levels in saliva.


Plasma sialic-acid index of apolipoprotein J (SIJ): a new alcohol intake marker.
Although plasma carbohydrate-deficient transferrin (CDT) is considered a viable biochemical marker for chronic alcohol consumption, it is valid only when an individual's daily alcohol consumption exceeds 60 g. In addition, it is less sensitive in women drinkers than in men drinkers. We have established that chronic alcohol consumption impairs the hepatic sialylation of a number of glycoproteins by specifically down-regulating Gal-beta-1,4GlcNAc alpha2,6-sialyltransferase mRNA. Significantly, we found that chronic ethanol consumption markedly inhibits hepatic sialylation of apolipoprotein J (Apo J), a 70-kDa N-glycosylated protein of plasma HDL. Because the sialic-acid index of Apo J (SIJ; moles of sialic acid per mole of Apo J protein) is approximately seven times more than that for transferrin (28 vs. 4), we have evaluated whether plasma SIJ would be an even more sensitive marker for chronic ethanol consumption than CDT in both rats and human subjects. The method involves immunoaffinity purification of plasma HDL-Apo J, followed by its sialic acid determination. We have found that chronic ethanol feeding resulted in loss of sialic acid residues of plasma HDL-Apo J in rats. This loss of sialic acid was positively correlated with both amount and duration of ethanol treatment. In human subjects, an intake of about 60 g of alcohol for 30 days led to almost 50% (P <.01) depletion of sialic acid from plasma HDL-Apo J. Further, we established that there was a positive correlation of alteration in SIJ with alcohol consumption, detoxification, abstinence, and relapse in human alcohol-dependent patients (sensitivity, 90%-92%). In addition, plasma SIJ was decreased by 50%-57% (P <.01) in both male and female alcohol-dependent subjects. We suggest that plasma SIJ can be used as a viable marker for early detection of chronic alcohol consumption in human beings.


Plasma testosterone in nursing home men.
Plasma testosterone (T) was measured at 8-9 a.m. in 44 men chronically institutionalized in a Veterans Administration Nursing Home, and correlated with an extensive clinical data base (including age, diagnoses, drugs, laboratory tests, anthropometric measurements, and mortality during the year after the T analysis). Age averaged 76.4 years (range 60-95). Plasma T was below the lower limit of the normal range for healthy young men (i.e. less than 300 ng/dl) in 46% of the men studied. Samples containing low T (less than 300 ng/dl) also contained subnormal unbound T, but normal concentrations of thyroxine and cortisol. Of the low T samples, 45% contained elevated LH, FSH or both (over 20 mU/ml), and the remaining 55% contained LH and FSH levels below this threshold, these two subgroups representing peripheral and central hypogonadism respectively. Plasma T was significantly (p less than 0.02) correlated in a direct relationship with hemoglobin, serum cholesterol, and the occurrence of seizures.


Determination of ivermectin and transformation products in environmental waters using hollow fibre-supported liquid membrane extraction and liquid chromatography-mass spectrometry/mass spectrometry.
A simple and easy-to-use extraction method for aqueous samples based on hollow fibre-supported liquid membrane (HF-SLM) followed by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) was developed to determine ivermectin and transformation products, the monosaccharide (TP1) and the aglycon of ivermectin (TP2). The proposed method attained enrichment factors up to 80, after optimising parameters, such as fibre length, organic solvent, stirring speed, salt level, pH in samples/fibre, extraction time and fibre emptying technique. Method validation with tap and lake water samples provided good linearity and detection limits of 0.2, 1.6 and 0.9 microg/l for ivermectin, TP1 and TP2 in lake water with RSD below 15%.


Anatomopathological and immunohistochemical study of explanted cryopreserved arteries.
The aim of the study was to analyze the mechanism of deterioration of implanted arteries. Eleven patients were included. Samples of vascular segments obtained from multiorgan donors and samples of the same vascular segments after explantation in the recipient were analyzed. Blood group, time of cold and warm ischemia, cause of death, time spent in the intensive care unit, time of storage of the cryopreserved grafts, and anatomopathological and immunohistochemical studies were analyzed using the preimplant samples obtained from the multiorgan donor. For samples obtained from the recipient, blood group, duration for which the tissue from the donor has been implanted, reason for graft explantation, and anatomopathological and immunohistochemical studies were analyzed. Histopathologically, the main finding has been the substitution of the muscular cap of the arterial wall by an intense fibrosis, in most of the cases, of a symmetrical nature. Besides this degeneration of myocytes, there is marked perivascular fibrosis and fibrointimal thickening also exists. The T lymphocytes suggest the importance of the immunological mechanism in the distortion of the architecture of the arteries. The atherosclerosis plays a less relevant role. Evidence of immune-mediated injury was found, and this mechanism seems to be responsible for the degenerative process in cryopreserved homografts.


Depolymerization of crystalline cellulose catalyzed by acidic ionic liquids grafted onto sponge-like nanoporous polymers.
The acidic ionic liquid (IL) functionalized polymer (PDVB-SO3H-[C3vim][SO3CF3]) possesses abundant nanoporous structures, strong acid strength and unique capability for deconstruction of crystalline cellulose into sugars in ILs. The polymer shows much improved catalytic activities in comparison with mineral acids, homogeneous acidic ionic liquids and the acidic resins such as Amberlyst 15. The enhanced catalytic activity found in the polymer is attributed to synergistic effects between the strongly acidic group and the ILs grafted onto the polymer, which by itself is capable of breaking down the crystalline structures of cellulose. This study may help develop cost-effective and green routes for conversion of biomass to fuels.


Assembly and export of a Toxoplasma microneme complex in Giardia lamblia.
The microneme proteins of Toxoplasma gondii belong to a large family of adhesins of apicomplexan parasites involved in motility and host cell invasion. During secretory transport, soluble micronemes associate with membrane-bound carriers/escorters and become exposed on the parasite surface as complexes with an array of adhesive domains. Previously, we have exploited the intestinal protozoan Giardia lamblia as an expression system to produce correctly folded and unglycosylated monomeric surface proteins of T. gondii. Here, we report assembly and export of a trimeric microneme (MIC1/4/6) adhesin complex from Toxoplasma. Co-expressed, recombinant microneme proteins were used to investigate structural requirements for microneme complex formation. In addition, export of a microneme subunit induced development of novel Golgi-like compartments demonstrating the existence of post endoplasmic reticulum structures involved in constitutive secretion in this 'Golgi-less' cell. Recreation of the trimeric microneme escorter-cargo system in Giardia is a versatile tool to analyse universal requirements for complex assembly, receptor-ligand interactions and Golgi neogenesis in the basal Giardia secretory system.


Recent advances in estrogen receptor-targeted probes conjugated to BODIPY dyes.
Estrogens, is a class of steroid hormones associated with the occurrence and development of breast cancer, that bind to estrogen receptors (ER). The development of BODIPY-based fluorescent ligands for the ER has continued to gain tremendous attention over the past 20 years. This review focuses on the synthesis methods, optical properties, and biological activity of BODIPY fluorescent probes conjugated to ER ligands. These will provide new strategy for designing fluorescent probes for targeting estrogen receptors.


Biochemical study of muscle samples from chicken embryos affected by Wofatox 50 EC.
On day 12 of incubation 0.4% and 4.0% aqueous emulsions of Wofatox 50 EC (50% methylparathion) were injected into the air space of the chicken egg. The eggs were opened on the day 19 of incubation and samples were obtained from both cervical and femoral muscles. Atrophy was found only in the cervical muscles by light microscopic evaluation. It is known that the inhibition of acetylcholine esterase causes a permanent inflow and accumulation of Ca2+ especially in the cervical muscle due to the increased mass and energy utilization in the last period before hatching. Changes in the activity of creatine kinase were expressed in a decreased creatine and creatine-phosphate content.


Changes of working conditions and job-related challenges due to the SARS-CoV-2 pandemic for medical assistants in general practices in Germany: a qualitative study.
In Germany, general practices are usually contacted first by patients with health complaints, including symptoms characteristic of SARS-CoV-2. Within general practices, medical assistants (MAs) are the first contact person for patients and perform various tasks in close physical patient contact. Working conditions of MAs have been characterized as challenging, e.g., due to low salaries, a high workload, time pressure and frequent interruptions. The potential changes of working conditions and job-related challenges experienced by MAs due to the SARS-CoV-2 pandemic have not been fully explored. We aimed to address this knowledge gap among MAs working in general practices in Germany. Semi-structured telephone interviews were conducted between March and April 2021 with 24 MAs. Medical assistants of legal age, who worked in general practices in Germany, and who were continuously employed and without change of employer in 2020 were eligible for participation. Interview recordings were transcribed verbatim and content-analyzed using MAXQDA, using deductive and inductive coding. The SARS-CoV-2 pandemic posed great challenges for MAs, including a dramatic increase in workload, changes in occupational tasks, increased hygiene measures, rearrangements of work organization, childcare issues, and structural and personnel challenges within their practice. Participants described both improved but also worsened collaboration with their employers and colleagues due to the pandemic. Many MAs complained about issues regarding SARS-CoV-2-related billing processes and an increase in unpleasant patient behavior, including disregard of practice rules or frequent verbal insults. Many also did not feel adequately appreciated by politics, media, or society for their efforts during the pandemic. Positive changes were perceived to be the expansion of digital communication channels and a growing social cohesiveness of practice teams. Our study suggests that the SARS-CoV-2 pandemic posed great challenges for MAs. The pandemic seems to have worsened MAs' working conditions, which had been described as challenging already prior to the pandemic. In order to improve job satisfaction and to prevent loss of healthcare personnel, measures must be taken to improve working conditions of MAs in general practices.


Radiosensitization by pemetrexed of human colon carcinoma cells in different cell cycle phases.
The novel folate antimetabolite Alimta (pemetrexed disodium, LY231514) exhibits antitumor activity in a broad array of human malignancies and was recently found to enhance radiation-induced cell killing in vitro. In the present study, a possible cell cycle phase-specific radiosensitization by pemetrexed was assessed. Widr human colon carcinoma cells were synchronized by serum withdrawal/stimulation that yielded about 80% cells with G1 DNA content 6 h after replating and more than 60% S-phase cells after 22 h, as assessed by flow cytometry. The respective cultures were irradiated with doses up to 12 Gy in combination with a subtoxic pemetrexed exposure (1.06 microM for 2 h: about 80% survival), or after mock treatment. Survival curves were generated by the clonogenic assay; apoptosis was measured by sub-G1 DNA flow cytometry. The combination treatment of the G1 cells and of the more radioresistant S-phase cell preparations yielded survival rates that were lower than expected for independent cell killing. Radiosensitization, calculated as the ratio of the mean inactivation doses without or with drug exposure (enhancement ratio), was not significantly different for the two cell preparations (enhancement ratio of 2.1 and 2.3, respectively) and was similar to the previously reported value for log-phase cells. Pemetrexed exposure was unable to stimulate an apoptotic response of these cells to radiation. Radiosensitization by pemetrexed is not cell cycle phase-specific, and the relative radioresistance of S-phase cells is retained. Apoptosis seems to have no influence on radiosensitization in this cell line.


Predicting mortality in patients with bleeding peptic ulcers after therapeutic endoscopy.
Despite advances in management of patients with bleeding peptic ulcers, mortality is still 10%. This study aimed to identify predictive factors and to develop a prediction model for mortality among patients with bleeding peptic ulcers. Consecutive patients with endoscopic stigmata of active bleeding, visible vessels, or adherent clots were recruited, and risk factors for mortality were identified in this deprivation cohort by using multiple stepwise logistic regression. A prediction model was then built on the basis of these factors and validated in the evaluation cohort. From 1993 to 2003, 3220 patients with bleeding peptic ulcers were treated. Two hundred eighty-four of the patients developed rebleeding (8.8%); emergency surgery was performed on 47 of these patients, whereas others were managed with endoscopic retreatment. Two hundred twenty-nine of these sustained in-hospital death (7.1%). In patients older than 70 years, presence of comorbidity, more than 1 listed comorbidity, hematemesis on presentation, systolic blood pressure below 100 mm Hg, in-hospital bleeding, rebleeding, and need for surgery were significant predictors for mortality. Helicobacter pylori-related ulcers had lower risk of mortality. The receiver operating characteristic curve comparing the prediction of mortality with actual mortality showed an area under the curve of 0.842. From 2004 to 2006, data were collected prospectively from a second cohort of patients with bleeding peptic ulcers, and mortality was predicted by using the model developed. The receiver operating characteristic curve showed an area under the curve of 0.729. Among patients with bleeding peptic ulcers after endoscopic hemostasis, advanced age, presence of listed comorbidity, multiple comorbidities, hypovolemic shock, in-hospital bleeding, rebleeding, and need for surgery successfully predicted in-hospital mortality.


The src-family kinase inhibitor PP2 suppresses the in vitro invasive phenotype of bladder carcinoma cells via modulation of Akt.
To evaluate PP2 as a modulator of the cadherin/catenin complex in late-stage bladder carcinoma cells, and to assess its potential invasion-suppressor activity in this model. A panel of five human bladder carcinoma cells, characterizing late-stage disease, was used to determine the concentration for 50% inhibition of PP2 in cell-proliferation assays. Modulation of cadherin/catenin expression by PP2 was determined in Western blot analysis, with an assessment of the activation status of mitogen-activated protein kinase and Akt signalling pathways. Altered invasive capacity linked to these variables was determined in standard in vitro invasion assays. PP2 elicited concentration-dependent growth inhibition in all bladder cell lines within the panel, with growth suppression recorded at 10-35 micromol/L PP2. Distinct morphological changes were recorded in cell lines exposed to PP2, accompanied by up-regulation of plakoglobin expression in a subset of lines. Exposure of cells to PP2 resulted in inactivation of Akt in all cells and a concomitant reduction in in vitro invasive capacity. These results show that PP2 inhibits bladder carcinoma cell growth and can modulate plakoglobin expression in a subset of cell lines. In addition, PP2 can suppress the in vitro invasive capacity of bladder carcinoma cells by modulating the activation status of Akt.


The effect of MTADN on 10 Enterococcus faecalis isolates and biofilm: an in vitro study.
Enterococcus faecalis is frequently isolated from both secondary and persistent root canal infections. MTAD is an effective intracanal irrigant, but its bactericidal activity requires improvement. The goal of this study was to investigate whether nisin, an antibacterial peptide, improves the antibacterial and antibiofilm activities of MTAD against E. faecalis clinical isolates. Ten E. faecalis strains were isolated from root canals with persistent periapical lesions. The antibacterial activity of MTAD, MTADN (nisin in combination with doxycycline), and MTAN (nisin in place of doxycycline) against E. faecalis isolates was evaluated using minimal inhibitory concentration and minimal bactericidal concentration assays. Scanning electron microscopy was used to observe E. faecalis biofilms on the chamber surface of the root canal, and confocal laser scanning microscopy was used to show the antibiofilm activity of the 3 irrigants. Ten E. faecalis strains were successfully isolated from clinical samples by selective medium, colony morphology, oxygen tolerance, bile resistance, Gram staining characteristics, and polymerase chain reaction identification. The antimicrobials MTAD, MTADN, and MTAN had different antibacterial activities against the 10 E. faecalis isolates, with MTADN showing superior antibacterial efficacy compared with MTAD. Strain D had the greatest sensitivity to MTAD and MTADN, whereas strain E was the most resistant to these compounds. Strain E was able to form a mature biofilm with complex architecture. Importantly, confocal laser scanning microscopic images showed that MTADN was able to kill completely E. faecalis isolates grown as a biofilm, whereas MTAD was unable to do so. MTADN effectively inhibited both the growth of E. faecalis root canal isolates and these isolates' biofilms. These results are encouraging and suggest that MTADN has a considerable potential for use as an effective irrigant.


Deciphering the immunoboosting potential of macro and micronutrients in COVID support therapy.
The immune system protects human health from the effects of pathogenic organisms; however, its activity is affected when individuals become infected. These activities require a series of molecules, substrates, and energy sources that are derived from diets. The consumed nutrients from diets help to enhance the immunity of infected individuals as it relates to COVID-19 patients. This study aims to review and highlight requirement and role of macro- and micronutrients of COVID-19 patients in enhancing their immune systems. Series of studies were found to have demonstrated the enhancing potentials of macronutrients (carbohydrates, proteins, and fats) and micronutrients (vitamins, copper, zinc, iron, calcium, magnesium, and selenium) in supporting the immune system's fight against respiratory infections. Each of these nutrients performs a vital role as an antiviral defense in COVID-19 patients. Appropriate consumption or intake of dietary sources that yield these nutrients will help provide the daily requirement to support the immune system in its fight against pathogenic viruses such as COVID-19.


Circadian rhythms and tumor growth.
Hormone secretion, metabolism, and the cell cycle are under rhythmic control. Lack of rhythmic control has been predicted to lead to uncontrolled proliferation and cancer. Consistent with this prediction are findings that circadian disruption by dim light at night or chronic jet lag accelerates tumor growth in desynchronized animals. Circadian controlled factors such as insulin/IGF-1, glucocorticoids, catecholamines, and melatonin have be implicated in controlling tumor growth in the desynchronized animals. Recent attention has focused on the signaling pathways activated by the circadian controlled factors because these pathways hold the potential for the development of novel strategies for cancer prevention and treatment.


Draft genome sequence of first monocot-halophytic species Oryza coarctata reveals stress-specific genes.
Oryza coarctata (KKLL; 2n = 4x = 48, 665 Mb) also known as Porteresia coarctata is an extreme halophyte species of genus Oryza. Using Illumina and Nanopore reads, we achieved the assembled genome size of 569.9 Mb, accounting 85.69% of the estimated genome size with N50 of 1.85 Mb and 19.89% repetitive region. We also found 230,968 simple sequence repeats (SSRs) and 5,512 non-coding RNAs (ncRNAs). The functional annotation of predicted 33,627 protein-coding genes and 4,916 transcription factors revealed that high salinity adaptation of this species is due to the exclusive or excessive presence of stress-specific genes as compared to rice. We have identified 8 homologs to salt-tolerant SOS1 genes, one of the three main components of salt overly sensitive (SOS) signal pathway. On the other hand, the phylogenetic analysis of the assembled chloroplast (134.75 kb) and mitochondrial genome (491.06 kb) favours the conservative nature of these organelle genomes within Oryza taxon.


Evaluation of disulfiram in the treatment of alcoholism.
Seventy five male patients with the diagnosis of alcohol dependence syndrome were given disulfiram and an alcohol challenge was administered to all of them. They were kept on maintenance dose of the drug and followed up for six months, note being made of their improvement on several parameters, viz. the number of drinking episodes, the sevarity of reaction suffered, the side effects experienced etc. Twenty one patients were considered as drop outs and four were abstainent without the aid of the drug. 54 % of the fifty patients who continued taking the drug showed good to moderate improvement. 42% had one or more drinking episode while consuming the tablets. Older patients, and those brought by relatives and friends did better than the others. Results are discussed.


Anticoagulant activity of dextran derivatives. Part I: Synthesis and characterization.
Substituted dextrans bearing carboxymethyl and benzylsulphonate groups have been prepared. These materials exhibit an antithrombic activity correlated with the ratio of each substituent. The highest activity is obtained when the dextran derivative contains more than 50% of carboxylic acid groups and simultaneously about 15% of benzylsulphonate functions.


Substitution of artificial colloids for fresh frozen plasma in pediatric cardiopulmonary bypass surgery.
In many centers, fresh frozen plasma is generally used as the main component of pump prime in pediatric cardiopulmonary bypass. However, many factors have resulted in stringent control of plasma transfusion and prompted the study of safe and efficient substitutes. The aim of this study was to investigate the feasibility of a priming strategy with gelatin during cardiopulmonary bypass in pediatric patients undergoing cardiac surgery and identify the factors associated with postoperative chest-tube drainage. We reviewed 1164 pediatric patients who underwent cardiac surgery with cardiopulmonary bypass between January 2012 and April 2013 in Fuwai hospital. Infants and children were primed with different types of solution: plasma or gelatin. Clinical data included postoperative coagulation function (pharmacological agents, chest-tube drainage, and transfusion requirements), recovery indicators (mechanical ventilator time, ICU stay and hospital stay), incidence of in-hospital mortality, and morbidity. Multivariate linear regression analysis was used to identify factors correlated with postoperative chest-tube drainage. No difference in mortality or morbidity was found between the plasma and gelatin groups. In infants, increased chest-tube drainage (postoperation 12 hours, median difference -0.046 ml/kg/hr, 95%CI: -0.105 to -0.007, P = 0.001; postoperation 24 hours, median difference -0.047 ml/kg/hr, 95%CI: -0.081 to -0.025, P < 0.001), and decreased transfusion (red blood cell, median difference 0.00 ml/kg/hr, 95%CI: 0.000-100, P < 0.001; fresh frozen plasma, median difference 5.556 ml/kg/hr, 95%CI: 2.30-8.333, P = 0.001), and recovery time (mechanical ventilator time, median difference 3.00 hours, 95%CI: 1.00-5.500, P < 0.001; ICU stay, median difference 17.00 hours, 95%CI: 1.00-22.000, P = 0.001; hospital stay, median difference 1.00 day, 95%CI: 0.00-2.000, P = 0.038) were demonstrated in the gelatin group. In children, the transfusion requirements (red blood cell, median difference 100 ml, P < 0.001;fresh frozen plasma, median difference 1.11 ml/kg, 95%CI: 0.000-2.42, P = 0.001) were decreased in the gelatin group. Multivariate linear regression analysis revealed that the type of priming solution (β = 1.940,95%CI: 1.057-2.823,P < 0.001), bypass time (β = 0.024, 95%CI: 0.013-0.036, P < 0.001), and age (β = -0.257, 95%CI: -0.422 to -0.09, P = 0.002) were independent variables correlating with chest-tube drainage in infants. In the general pediatric patients undergoing elective cardiac surgery, substitution of gelatin for fresh frozen plasma in cardiopulmonary bypass is feasible.


Intravenous immunoglobulin in heart transplant recipients with mild to moderate hypogammaglobulinemia and infection.
Hypogammaglobulinemia (HGG) is a complication of solid organ transplantation leading to increased risk of infections. Intravenous immunoglobulin G (IVIG) replacement in patients with HGG may be able to reduce risk and morbidity associated with infection; however, there is scarce data about IVIG in mild to moderate HGG (IgG 400-700 mg/dl) and heart transplant recipients. A single center, retrospective study was performed in heart transplant recipients with mild (IgG 500-700 mg/dl) to moderate (IgG 400-499 mg/dl) HGG in the presence of an infection. Forty-two patients were included in this study; 19 patients (45.2%) received IVIG and 23 (54.8%) patients did not. Patients in the IVIG group received on average one dose of IVIG at 0.5 g/kg. No differences in incidence of new infection at 3 months (26.3% vs. 17.4%; P = .71) and 6 months (42.1% vs. 34.8%; P = .63) were observed between the IVIG and non-IVIG groups. Infections based on mild or moderate HGG also had no differences at 3 and 6 months. Our findings suggest that a single infusion of IVIG in mild to moderate HGG may have little to no benefit in reducing incidence of new infections. Larger prospective studies are needed to confirm these findings.


Pericardial cysts in children: surgical or conservative approach?
The authors present a case of an 11-year-old boy with a history of mild asthma and cough who underwent radiographic examination of the chest. The radiograph showed a round, discrete mass in the right cardiophrenic angle. The patient underwent thoracoscopic excision, and histologic examination found a unilocular, pericardial cyst. The possible causes of mediastinal masses and an argument for their surgical removal is presented.


Biomarkers as molecular targets of drug interventions.
To present an overview of biomarkers used in a multiplicity of roles, including as targets of therapeutic intervention for several organ sites. Journal articles and book chapters from medical and nursing literature, and internet resources. A single molecular marker may function in a variety of roles (ie, markers of risk, diagnostics, prognostics, intermediate endpoints). In some instances the molecule can also function as a target of therapeutic intervention. Nursing implications include a better understanding of the nature of biomarkers and the multiplicity of their applications, especially with regard to therapeutic targets.


Tumor hyaluronan as a novel biomarker in non-small cell lung cancer: A retrospective study.
Hyaluronan (HA) accumulation is associated with tumorigenesis and aggressive tumor behavior. We investigated the biomarker potential of HA in non-small cell lung cancer (NSCLC). HA levels were scored using affinity histochemistry in 137 NSCLC samples stratified by HA score ≤10, 11-20, 21-30, and >30 with HA-high defined as ≥25% expression in the extracellular matrix (ECM) of the tumor surface area. Overall survival (OS) and time to progression from initiation of taxane therapy (TTP) were compared using log-rank tests based on HA score. Of 122 patients with recurrent/metastatic NSCLC, 93 had mean HA scores that were not significantly different across clinicopathologic variables. Frequency of HA-high tumors did not differ by histology (34/68 adenocarcinomas vs. 12/25 squamous tumors, Fisher's p = 1.0000). Median OS for recurrent/metastatic adenocarcinoma was 35.5 months (95%, 23.6-50.3) vs. 17.9 months for squamous (95%, 12.7-37.0, log-rank test, p = 0.0165). OS was not significantly different by HA quartiles, high or low (<25) HA score and tumor histology, and HA biopsy site (all p > 0.05). Median TTP (n = 98) significantly differed by HA quartile (2.8 months for HA score ≤10; 5.0 months for 11-20; 7.9 months for 21-30; 3.9 months for >30, p = 0.0265). Improved TTP trended in HA-high over HA-low tumors (n = 98, p = 0.0911). In this NSCLC cohort, tumor HA level represents a potential biomarker for TTP, which remains a cornerstone of NSCLC therapy. Further validation is warranted to identify the HA accumulation threshold associated with clinical benefit.


High-order harmonics generation in the laser-induced lead-free perovskites-containing plasmas.
High-order harmonics generation in the laser-induced plasmas produced on the surfaces of lead-free perovskites is studied. We analyze the harmonics generation in (CH3NH3)2CuCl4 and (CH3NH3)2CuBr4 plasmas during their ablation by the femtosecond, picosecond, and nanosecond pulses. The modifications of the high-order harmonics spectra are studied using the -color pump scheme (800 nm and 400 nm, 40 fs pulses). The influence of the variations of laser chirp and pulse duration on the dynamics of high-order harmonics generation is examined. The spectral shift, chirp-related harmonic cutoff scaling, and the role of the pulse duration of converting and heating laser radiation are examined at different conditions of plasma formation and harmonic generation. The dependencies of the pulse duration and the fluence of heating pulses on the harmonic's blue shift are found. The effect of harmonics broadening and splitting on the two red- and blue-shifted components is demonstrated.


Gastric carcinoma survival at the Pennsylvania Hospital -- 1964 to 1974.
Despite major improvements in diagnosis, anesthesia, surgical techniques, and postoperative care, the survival rate for adenocarcinoma of the stomach remains a dismal one. In our series of 109 patients, almost all patients seen were diagnosed too late to effect any kind of surgical care. In the period from January 1964, to December 1974, 122 patients were admitted to Pennsylvania Hospital with a diagnosis of gastric adenocarcinoma. Of the 109 patients followed to their death, only seven survived 5 years; the longest survival was 80 months. Among the 33 patients not resected, median survival was only one month. Of the 74 patients who had surgical resections survival ranged from a median of 5.5 months for those who had total gastrectomy to a median of 8 months for those receiving subtotal gastrectomy.


Serum, Dietary, and Supplemental Vitamin D Levels and Insulin Resistance in 6294 Randomly Selected, Non-Diabetic U.S. Adults.
The primary aim of this study was to determine the associations between serum, dietary, and supplemental vitamin D levels and insulin resistance in 6294 non-diabetic U.S. adults. A total of 8 years of data from the 2011−2018 National Health and Nutrition Examination Survey (NHANES) and a cross-sectional design were utilized to answer the research questions. Serum vitamin D levels were quantified using high-performance liquid chromatography−tandem mass spectrometry. Dietary and supplemental vitamin D intakes were assessed using the average of two 24 h dietary recalls taken 3−10 days apart. The homeostatic model assessment (HOMA), based on fasting glucose and fasting insulin levels, was employed to index insulin resistance. Demographic covariates were age, sex, race, and year of assessment. Differences in physical activity, body mass index (BMI), cigarette smoking, body weight, season, and energy intake were also controlled statistically. Serum levels of vitamin D differed significantly, and in a dose−response order, across quartiles of HOMA-IR, after adjusting for year, age, sex, and race (F = 30.3, p < 0.0001) and with all the covariates controlled (F = 5.4, p = 0.0029). Dietary vitamin D levels differed similarly across HOMA-IR quartiles, but to a lesser extent, respectively (F = 8.1, p = 0.0001; F = 2.9, p = 0.0437). Likewise, supplemental vitamin D levels also differed across the HOMA-IR quartiles, respectively (F = 3.5, p = 0.0205; F = 3.3, p = 0.0272). With all the covariates controlled, the odds of having insulin resistance were significantly greater for those in the lowest quartile of serum and supplemental vitamin D intake compared to the other quartiles combined. In conclusion, in this nationally representative sample, serum, dietary, and supplemental vitamin D were each predictive of insulin resistance, especially in those with low serum levels and those with no supplemental intake of vitamin D.


Contrast ultrasound imaging of the aorta alters vascular morphology and circulating von Willebrand factor in hypercholesterolemic rabbits.
Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol-fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. After adjustment for pre-exposure vWF, high-level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; P(adj) < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.


Effects of prenatal stress on sexual partner preference in mice.
Three-month old, male Swiss Webster mice were born to either control dams or dams who had been prenatally stressed with light, heat, noise and handling during the last week of gestation. As adults, male offspring were tested on sexual partner preference and sexual behavior (mounting, intromissions and lordosis) with a sexually experienced male stimulus animal and a stimulus estrous female. In comparison to males born to control dams, prenatally stressed males showed a sexual partner preference for the sexually active male as demonstrated by a negative partner preference score, more and longer visits to the male's compartment, fewer and shorter visits to the female's compartment and longer latencies to and lower frequencies of mounts and intromissions of females. In addition, stressed males showed a greater frequency of lordosis and a higher lordosis quotient than did control males. This study is the first to investigate the effects of prenatal stress alone, without hormonal manipulation, on sexual partner preference using both a partner preference paradigm and measures of sexual behavior such as mounting, intromissions and lordosis. These findings support the suggestion that prenatal stress alone is enough to significantly affect sexual partner preference in male mice.


Optimizing the logistics of anaerobic digestion of manure.
Electrical power production from the combustion of biogas from anaerobic digestion (AD) of manure is a means of recovering energy from animal waste. We evaluate the lowest cost method of moving material to and from centralized AD plants serving multiple confined feeding operations. Two areas are modeled, Lethbridge County, Alberta, Canada, an area of concentrated beef cattle feedlots, and Red Deer County, Alberta, a mixed-farming area with hog, dairy, chicken and beef cattle farms, and feedlots. We evaluate two types of AD plant: ones that return digestate to the source confined feeding operation for land spreading (current technology), and ones that process digestate to produce solid fertilizer and a dischargeable water stream (technology under development). We evaluate manure and digestate trucking, trucking of manure with return of digestate by pipelines, and pipelining of manure plus digestate. We compare the overall cost of power from these scenarios to farm or feedlot-based AD units. For a centralized AD plant with digestate return for land spreading the most economical transport option for manure plus digestate is by truck for the mixed-farming area and by pipelines for the concentrated feedlot area. For a centralized AD plant with digestate processing, the most economical transport option is trucking of manure for both cases.However, for the concentrated feedlot area, pipeline transport of manure is close in cost to trucking, and the impact of truck congestion would likely lead to selection of pipeline transport. For the mixed-farming area, centralized AD is more economical than for any individual farm or feedlot unit. For the concentrated feedlot area, a centralized AD plant is less economical than a feedlot-based AD unit more than 55,000 head (digestate return) and 300,000 head (digestate processing). The study demonstrates the viability of centralized AD plants vs farm-based units in most farming environments, and that careful analysis of the cost of pipeline vs truck transport of manure and digestate is required on a case-by-case basis.


Identification and analysis of key hypoxia- and immune-related genes in hypertrophic cardiomyopathy.
Hypertrophic cardiomyopathy (HCM), an autosomal dominant genetic disease, is the main cause of sudden death in adolescents and athletes globally. Hypoxia and immune factors have been revealed to be related to the pathology of HCM. There is growing evidence of a role for hypoxia and inflammation as triggers and enhancers in the pathology in HCM. However, the role of hypoxia- and immune-related genes in HCM have not been reported. Firstly, we obtained four HCM-related datasets from the Gene Expression Omnibus (GEO) database for differential expression analysis. Immune cells significantly expressed in normal samples and HCM were then screened by a microenvironmental cell population counter (MCP-counter) algorithm. Next, hypoxia- and immune-related genes were screened by the LASSO + support vector machine recursive feature elimination (SVM-RFE) and weighted gene co-expression network analysis (WGCNA). Single-gene enrichment analysis and expression validation of key genes were then performed. Finally, we constructed a competing endogenous RNA (ceRNA) network of key genes. In this study, 35 differentially expressed hypoxia genes were found. By using LASSO + SVM-RFE analysis, 10 more targets with differentially expressed hypoxia genes were identified. The MCP-count algorithm yielded five differentially expressed immune cells, and after assessing them for WGCNA characteristics, 612 immune genes were discovered. When hypoxia and immune genes were combined for cross-tabulation analysis, three hypoxia- and immune-related genes (ATP2A2, DDAH1, and OMA1) were identified. Based on hypoxia characteristic genes, three key genes were identified. These were also significantly related to immune activation, which proves a theoretical basis and reference value for studying the relationship between HCM and hypoxia and immunity.


10-Year All-Cause Mortality Following Percutaneous or Surgical Revascularization in Patients With Heavy Calcification.
The aim of this study was to assess 10-year all-cause mortality in patients with heavily calcified lesions (HCLs) undergoing percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG). Limited data are available on very long term outcomes in patients with HCLs according to the mode of revascularization. This substudy of the SYNTAXES (Synergy Between PCI With Taxus and Cardiac Surgery Extended Survival) study assessed 10-year all-cause mortality according to the presence of HCLs within lesions with >50% diameter stenosis and identified during the calculation of the anatomical SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) score among 1,800 patients with the 3-vessel disease and/or left main disease randomized to PCI or CABG in the SYNTAX trial. Patients with HCLs were further stratified according to disease type (3-vessel disease or left main disease) and assigned treatment (PCI or CABG). The 532 patients with ≥1 HCL had a higher crude mortality rate at 10 years than those without (36.4% vs 22.3%; HR: 1.79; 95% CI: 1.49-2.16; P < 0.001). After adjustment, an HCL remained an independent predictor of 10-year mortality (HR: 1.36; 95% CI: 1.09-1.69; P = 0.006). There was a significant interaction in mortality between treatment effect (PCI and CABG) and the presence or absence of HCLs (Pinteraction = 0.005). In patients without HCLs, mortality was significantly higher after PCI than after CABG (26.0% vs 18.8%; HR: 1.44; 95% CI: 0.97-1.41; P = 0.003), whereas in those with HCLs, there was no significant difference (34.0% vs 39.0%; HR: 0.85; 95% CI: 0.64-1.13; P = 0.264). At 10 years, the presence of an HCL was an independent predictor of mortality, with a similar prognosis following PCI or CABG. Whether HCLs require special consideration when deciding the mode of revascularization beyond their current contribution to the anatomical SYNTAX score deserves further evaluation. (Synergy Between PCI With TAXUS and Cardiac Surgery: SYNTAX Extended Survival [SYNTAXES], NCT03417050; SYNTAX Study: TAXUS Drug-Eluting Stent Versus Coronary Artery Bypass Surgery for the Treatment of Narrowed Arteries [SYNTAX], NCT00114972).


Hormonal regulation of hepatitis B virus gene expression: influence of androgen receptor.
Adult HBV-transgenic males produce more hepatitis B surface antigen (HBsAg) in serum than females. The difference decreases with castration and is restored with testosterone replacement. To investigate the contribution of the androgen receptor in this process, HBV-transgenic males were mated with females heterozygous for the testicular feminization mutation (Tfm), an X-linked gene with 90% reduced androgen receptor. A total of 19 phenotypic HBV-transgenic females were studied, of which eight XYTfm females were identified by the presence of Y-chromosome DNA using molecular hybridization. The 11 normal (XX) females had 11.7 +/- 3.5 micrograms/mL (mean +/- SD) of HBsAg in their serum, whereas the Tfm (XY) females had 17.1 +/- 5.9 micrograms/mL (p < 0.05). However, the Tfm (XY) females produced less HBsAg than 33 normal (XY) males (41 +/- 12 micrograms/mL), and the overall ratio of male/female HBsAg levels was reduced: XY/XX = 3 versus XYTfm/XX = 1.5. Although dexamethasone caused an increase in XYTfm and XX mice, testosterone did not increase HBsAg in XYTfm. These data indicate that hepatitis B expression as measured by HBsAg levels in this animal model is mediated through an androgen receptor.


Interleukin-36γ is expressed by neutrophils and can activate microglia, but has no role in experimental autoimmune encephalomyelitis.
Experimental autoimmune encephalomyelitis (EAE) is a model of inflammatory demyelinating diseases mediated by different types of leukocytes. How these cells communicate with each other to orchestrate autoimmune attacks is not fully understood, especially in the case of neutrophils, whose importance in EAE is newly established. The present study aimed to determine the expression pattern and role of different components of the IL-36 signaling pathway (IL-36α, IL-36β, IL-36γ, IL-36R) in EAE. EAE was induced by either active immunization with myelin peptide, passive transfer of myelin-reactive T cells or injection of pertussis toxin to transgenic 2D2 mice. The molecules of interest were analyzed using a combination of techniques, including quantitative real-time PCR (qRT-PCR), flow cytometry, Western blotting, in situ hybridization, and immunohistochemistry. Microglial cultures were treated with recombinant IL-36γ and analyzed using DNA microarrays. Different mouse strains were subjected to clinical evaluation and flow cytometric analysis in order to compare their susceptibility to EAE. Our observations indicate that both IL-36γ and IL-36R are strongly upregulated in nervous and hematopoietic tissues in different forms of EAE. IL-36γ is specifically expressed by neutrophils, while IL-36R is expressed by different immune cells, including microglia and other myeloid cells. In culture, microglia respond to recombinant IL-36γ by expressing molecules involved in neutrophil recruitment, such as Csf3, IL-1β, and Cxcl2. However, mice deficient in either IL-36γ or IL-36R develop similar clinical and histopathological signs of EAE compared to wild-type controls. This study identifies IL-36γ as a neutrophil-related cytokine that can potentially activate microglia, but that is only correlative and not contributory in EAE.


Radiotherapy for Resectable and Borderline Resectable Pancreas Cancer: When and Why?
The role of (chemo) radiation in the perioperative management of patients with resectable and borderline resectable pancreatic ductal adenocarcinoma is controversial. Herein, we review and interpret existing data relating to the ability of (chemo) radiation to "downstage" pancreatic tumors, delay recurrence, and prolong patients' survival. In sum, the evidence suggests that while neoadjuvant (chemo) radiation may impact pathologic metrics favorably, it rarely converts anatomically unresectable tumors to resectable ones. And while data do support the ability of (chemo)radiation to delay cancer progression, its ability to prolong longevity has not been confirmed. It is possible that (chemo)radiation is effective in prolonging the survival of select patients, but to date, this cohort remains undefined due to heterogeneity in both the populations studied and the regimens used to treat them. Based on our interpretation of existing data, we currently administer neoadjuvant and adjuvant (chemo)radiation selectively to patients with localized pancreatic cancer who we consider at highest risk for local progression. We may also use it as an alternative to pancreatectomy in patients who are poor candidates for surgery. Ultimately, the role of (chemo)radiation in these settings is evolving. Better studies of patients most likely to benefit from its local effects are necessary to clearly define its place within the perioperative treatment algorithms used for patients with localized pancreatic cancer.


Corrigendum to "Comparison of the Efficacy of Three Loading Doses of Intravitreal Injection of Conbercept with Injection Combined with PDT for the Treatment of PCV".
[This corrects the article DOI: 10.1155/2020/2428348.].


Metal coordination of azurin in the unfolded state.
1H NMR data applied to the paramagnetic cobalt(II) derivative of azurin from Pseudomonas aeruginosa have made it possible to show that the metal ion is bound to the protein in the unfolded state. The relaxation data as well as the low magnetic anisotropy of the metal ion indicate that the cobalt ion is tetrahedral in the unfolded form. The cobalt ligands have been identified as the residues Gly45, His46, Cys112 and His117. Met121 is not coordinated in the unfolded state. In this state, the metal ion is not constrained to adopt a bipyramidal geometry, as imposed by the protein when it is folded. This is clear confirmation of the rack-induced bonding mechanism previously proposed for the metal ion in azurin.


Visual resolution and receptive field size: examination of two kinds of cat retinal ganglion cell.
Intraocular recordings from brisk-sustained and brisk-transient ganglion cells in the cat's retina revealed a systematic increase in center size and decrease in spatial cut-off frequency with increasing distance from the area centralis. At any one eccentricity sizes of the centers of sustained and transient cells did not overlap, and the variation in cut-off frequency for each class was constrained to about one-half octave.


Computed tomographic features of nonthyroid extraocular muscle enlargement.
While Graves' disease is the most common cause of enlarged extraocular muscles, other disorders may masquerade as dysthyroid orbitopathy. The authors conducted a retrospective analysis of the computed tomographic (CT) scans of 60 patients with nonthyroid enlarged extraocular muscles to establish the differential radiographic features of these disorders. The diseases were classified as primary or local invasion of neoplasm (26%), inflammatory (25%), metastatic tumor (20%), vascular (13%), infection (12%), and acromegaly (3%). The inflammatory cases demonstrated more bilateral involvement (40%) and less involvement of the tendons (47%) than previously appreciated. The relatively high incidence of these features in the inflammatory group is important because both features have been considered pathognomonic for Graves' disease. Primary and metastatic tumors produced a nodular muscle enlargement with sharp borders and frequent bone changes. Certain tumors showed a predilection for certain muscle groups. Vascular cases involved multiple unilateral muscles and usually enlarged the superior ophthalmic vein. Infectious cases usually demonstrated fusiform muscle enlargement with blurred margins, whereas acromegaly caused moderate enlargement of all recti. Although certain diagnosis-specific radiographic patterns are described, no feature is pathognomonic for any disorder.


TRPM6 expression and cell proliferation are up-regulated by phosphorylation of ERK1/2 in renal epithelial cells.
Transient receptor potential melastatin 6 (TRPM6) is a magnesium channel and expressed in the intestine and renal distal tubules. Little is known about the regulatory mechanism of TRPM6 expression and the role of magnesium influx. EGF increased the phosphorylation of ERK1/2 and TRPM6 expression that were inhibited by U0126 in renal epithelial NRK-52E cells. Furthermore, EGF enhanced the influx of magnesium, whereas U0126 and TRPM6 siRNA inhibited it. EGF increased the proportion of cells in S phase, whereas U0126 and TRPM6 siRNA increased the proportion in G1 phase. The phosphorylation of ERK1/2 may up-regulate TRPM6 expression and magnesium influx, resulting in an increase in cell proliferation with a shift from G1 to S phase.


VapB as a regulator of osteoclastogenesis via modulation of PLCγ2-Ca(2+)-NFAT signaling.
VapB has been shown to regulate calcium homeostasis in amyotrophic lateral sclerosis. Calcium signaling is also important in metabolic bone diseases, but the role of VapB in the generation of osteoclasts for bone resorption during osteoclastogenesis is not known. Therefore, we investigated the role of VapB in RANKL-induced osteoclast differentiation. Interestingly, VapB is induced during osteoclastogenesis, and regulates osteoclast differentiation by modulating NFATc1. The results also suggest that VapB regulates osteoclastogenesis via PLCγ2-Ca(2+)-NFAT signaling. The involvement of PLCγ2-Ca(2+)-NFAT signaling in VapB-regulated osteoclastogenesis was confirmed by a pharmacological study. Taken together, the results indicate that VapB positively regulates RANKL-mediated osteoclastogenesis via PLCγ2-Ca(2+)-NFAT signaling.


Glanzmann Thrombasthenia in a Newborn with Heterozygous Factor V Leiden and Heterozygous MTHFR C677T Gene Mutations.
Glanzmann thrombasthenia is a rare congenital platelet dysfunction. A 2-day-old male neonate delivered at 35 weeks' gestation was referred with extensive bruising and jaundice. His elder sibling had Glanzmann thrombasthenia, and his mother had thrombophilic risk factors. Flow cytometric analysis revealed absent CD41/CD61. A molecular thrombophilia panel revealed the presence of heterozygous factor V Leiden G1691A and methylenetetrahydrofolate reductase C677T gene mutations. General precautions to avoid injuries and spontaneous bleeding were advised. Life-threatening bleeding may not be the first finding in cases of thrombasthenia accompanied by thrombophilic risk factors.


Regulatory changes that affect coding for immunotherapy.
During the past decade, a variety of federal regulations have had a significant impact on the way allergen immunotherapy is reimbursed and how Current Procedural Terminology (CPT) codes are used for this purpose. As mandated by the US Congress, the Centers for Medicare and Medicaid Services (CMS) through the Office of the Inspector General (OIG) targeted immunotherapy codes for scrutiny, because they are some of the most frequently used codes. To examine how federal regulations have affected reimbursement for allergy immunotherapy and other allergy services. A review was performed of the OIG survey of allergy immunotherapy and the OIG recommendations on CPT coding compliance guidelines. A preliminary survey found problems with medical appropriateness of allergen immunotherapy. For this reason, the OIG performed a more comprehensive study of 301 physicians using code 95165 to analyze by medical record and billing data whether the new billing rules were being correctly used and found that only 44% of physicians were following the new definition of a billable dose. In the early 1990s, the federal government served notice of its intent to more aggressively identify and prosecute health care providers who improperly billed and collected for medical services. Through the adoption of the 1991 US Sentencing Commission Guidelines, the government sought to enhance compliance by mandating lesser criminal penalties for violating organizations that nevertheless maintained and operated "effective compliance plans." In 2002, the OIG audited health care providers and recouped dollar 14.4 billion in improper payments by Medicare. Between January and June 2003, Medicare excluded 1,241 individual providers and health care entities due to fraudulent billing practices. Federal regulations have significantly affected reimbursement for allergy immunotherapy and other allergy services. Allergists need to be aware of these changes and implement the new recommendations into their practices.


Metabolism of chloral hydrate in the anoxic perfused liver.
The metabolism of chloral hydrate (CH) under anoxic conditions was investigated in the non-recirculating, hemoglobin-free liver perfusion system. CH uptake in the anoxic liver decreased to about 80% of that in the oxygen-supplied liver. The reduction of CH to trichloroethanol (TCE) increased and the oxidation of CH to trichloroacetic acid (TCA) decreased. The TCE/TCA ratio increased; however, the total trichloro compounds, that is TCE and TCA, were not significantly altered by anoxia. Though approximate 14% of the CH infused into the oxygen-supplied liver was changed to substances other than TCE or TCA, the unknown part was a very small portion in the anoxic liver. The decrease in CH uptake, by the anoxic liver, is thought to be equivalent to the decrease of the unknown metabolites. The TCE/TCA ratio under anoxia was also altered by pyruvate or lactate infusion.


Comparison of intralesional corticosteroid and propranolol treatment of periorbital infantile hemangiomas: an outcome study of 61 cases.
To compare intralesional corticosteroid (IC) injections with oral propranolol in children with periorbital infantile hemangioma (IH). Children were diagnosed with IH and treated with IC (n = 29) or propranolol (n = 14). In cases in which no further improvement was seen, treatment was stopped and the outcome measured. Type, duration, and complications of treatment and supportive or additional therapies were scored, along with outcomes of visual measurements, at the start and end of therapy. Twenty-one of the 29 children (72%) treated with IC injections were given a second injection and 16 (55%) were given more than two. Median duration of IC therapy was 15.9 months (interquartile range (IQR) 10.28), compared with 6.5 months (IQR 4.87) for propranolol (p<0.001). The complications reported after IC injections were bleeding (n = 9) and ulceration (n = 7). No complications were noted in the propranolol group. Additional therapy consisting of oral prednisolone therapy was applied in one child from the steroid-treated group. The levels of amblyopia and the median absolute improvement did not significantly differ between the groups. The IC injections and oral propranolol medication equally improved amblyopia in children with IH of the periorbital and cheek region; however, propranolol was associated with fewer complications and additional or supportive treatment was not indicated. We prefer oral propranolol medication over IC injections in cases in which IH threatens to hamper visual acuity.


Regulation of energy substrate utilization and hepatic insulin sensitivity by phosphatidylcholine transfer protein/StarD2.
Phosphatidylcholine transfer protein (PC-TP, also known as StarD2) is a highly specific intracellular lipid binding protein with accentuated expression in oxidative tissues. Here we show that decreased plasma concentrations of glucose and free fatty acids in fasting PC-TP-deficient (Pctp(-/-)) mice are attributable to increased hepatic insulin sensitivity. In hyperinsulinemic-euglycemic clamp studies, Pctp(-/-) mice exhibited profound reductions in hepatic glucose production, gluconeogenesis, glycogenolysis, and glucose cycling. These changes were explained in part by the lack of PC-TP expression in liver per se and in part by marked alterations in body fat composition. Reduced respiratory quotients in Pctp(-/-) mice were indicative of preferential fatty acid utilization for energy production in oxidative tissues. In the setting of decreased hepatic fatty acid synthesis, increased clearance rates of dietary triglycerides and increased hepatic triglyceride production rates reflected higher turnover in Pctp(-/-) mice. Collectively, these data support a key biological role for PC-TP in the regulation of energy substrate utilization.


Increase of c-jun mRNA upon hypo-osmotic cell swelling of rat hepatoma cells.
c-jun mRNA levels were increased in rat hepatoma cells (H4-II-E-C3) when exposed to hypotonic medium (205 mosmol/l) with a maximal induction observed after 1 h of hypotonic exposure. At this time point an approximate 5-fold increase in c-jun expression could be detected in relation to normotonic control incubations (305 mosmol/l). Hypertonic exposure (405 mosmol/l) had only a slight effect on c-jun expression. In contrast to the increased c-jun mRNA levels under hypotonic conditions, expression of the c-fos proto-oncogene was unaffected by changes in the osmolarity. The hypotonicity-induced increase in c-jun expression was also detectable in the presence of a protein kinase C (PKC) inhibitor. This indicates that PKC is not involved in the signal transduction pathway leading to c-jun expression upon hypotonic cell swelling in these cells.


Folylpolyglutamate synthesis in Neurospora crassa: primary structure of the folylpolyglutamate synthetase gene and elucidation of the met-6 mutation.
In Neurospora crassa, the met-6+ gene encodes folylpoly-gamma-glutamate synthetase (FPGS) which catalyzes the formation of polyglutamate forms of folate. Methionine auxotrophy of the Neurospora crassa met-6 mutant is related to a lesion affecting this enzyme. Functional complementation of the mutant strain was achieved by introducing copies of the wild-type met-6+ gene into mutant spheroplasts. The complementing sequences were found to be contained on a 3.5 kb EcoRI-BamHI restriction fragment. The nucleotide sequence of the met-6+ gene was determined and an open reading frame of 1587 bp was identified, interrupted by two introns. This open reading frame contained several AUG codons but translation beginning from either of the first two would theoretically produce a protein of appropriate size and with similarity to five other FPGS proteins. Northern blot analyses of met-6+ transcripts revealed a 2.0 kb product. The position of the transcription stop site and an intron were identified by sequencing partial cDNA clones which were truncated at the 5' end. DNA sequence analysis of the met-6 mutant allele revealed a T to C transition which would result in replacement of a highly conserved serine with a proline.


Edinger-Westphal nucleus: cholecystokinin immunocytochemistry and projections to spinal cord and trigeminal nucleus in the cat.
Immunocytochemical methods were used to determine the distribution of cells with cholecystokinin-like immunoreactivity (CCK-LI) in the cat Edinger-Westphal complex (EW). Numerous cells with CCK-LI are found throughout the length of EW. The distribution and frequency of such cells are similar to the pattern of EW neurons that show substance P-like immunoreactivity (SP-LI). Companion retrograde transport experiments reveal that EW neurons which project to spinal cord or the region of the caudal trigeminal nucleus are found throughout the length of EW, and that some EW neurons which project to spinal cord also show CCK-LI.


Site-specific microinjection of liposomes into the brain for local infusion of a short-lived peptide.
The short-lived peptide, angiotensin-(1-7) (Ang-(1-7)), was encapsulated in different liposome preparations, in order to evaluate the influence of membrane fluidity, membrane surface, liposome size and dose of peptide on the cardiovascular effects of the encapsulated peptide at a specific site of the brain. These preparations were microinjected unilaterally into the rostral ventrolateral medulla (RVLM) of Wistar rats, and mean arterial blood pressure (MAP) and heart rate (HR) were registered by telemetry. Pegylated, rigid and calibrated (200 nm) liposomes, containing 50 ng of Ang-(1-7), elicited a significant increase of MAP for at least 7 days, in contrast to empty liposomes or non-pegylated liposomes. When a two-fold higher peptide dose was employed or when pegylated liposomes were used in the fluid state or uncalibrated, less pronounced pressor effects were observed. These data show that the cardiovascular responses to the microinjection of Ang-(1-7)-containing liposomes into the RVLM can be modulated through the manipulation of liposome characteristics. These results can be explained by the influence of liposome characteristics on the flux of peptide release. It is expected that this new method will encounter numerous applications in the study of the chronic actions of short-lived bioactive peptides in specific sites of the brain.


Social comparisons on social media: online appearance-related activity and body dissatisfaction in adolescent girls.
Adolescents' engagement with online social networking platforms is advancing at an exponential rate and research is needed to investigate any impact on young users' mental health. This study examined appearance-related activity (e.g. looking at photos of friends) on social media and body dissatisfaction among adolescent girls. Self-report measures of online appearance-related activity, social comparisons to female target groups, internalization of the thin ideal, body dissatisfaction, and self-esteem were administered to 210 girls (mean age = 15.16 years). Body dissatisfaction was significantly related to (i) time spent engaged in social comparisons and (ii) upward social comparisons with various female targets while online. Evaluating oneself less favorably than the target group of close friends was most strongly associated with poorer body image appraisals. Serial multiple mediation analysis revealed that even after controlling for age and self-esteem, time spent engaged in social comparisons significantly mediated the relationship between online appearance-related activity and body dissatisfaction. This association was then further partially mediated by internalization of the thin ideal, which significantly mediated the relationship between time engaged in social comparisons and body dissatisfaction. Results are discussed in terms of online social media platforms representing an additional appearance culture environment for adolescent girls. The effects of this on the mental health of vulnerable users and how future research should investigate protective factors that may buffer young girls from the adverse effects of social media are considered.


HIV combination prevention and declining orphanhood among adolescents, Rakai, Uganda, 2001-18: an observational community cohort study.
Orphanhood increased markedly in the 1980s and 1990s in sub-Saharan Africa because of HIV-related mortality. Little is known about the contribution of HIV interventions, such as antiretroviral therapy (ART) and male medical circumcision, to more recent trends in orphanhood. In this study, we examined trends over time in maternal-only, paternal-only, and double orphanhood among adolescents before and after ART and male medical circumcision became widely available in the Rakai region of south-central Uganda. We sought to understand the association between adolescent orphanhood and HIV combination prevention (community-level ART use and prevalence of male medical circumcision). We hypothesised that increasing combination prevention, including greater use of ART and higher prevalence of male medical circumcision, would be associated with a lower probability of orphanhood. We examined the prevalence of orphanhood among adolescents aged 15-19 years, before and after roll-out of ART in mid-2004 and male medical circumcision in 2007, using data from 28 continuously followed communities within the Rakai Community Cohort Study. We used multinomial logistic regression with clustered SEs to estimate adjusted relative risk ratios (RRs) for maternal-only, paternal-only, and double orphanhood compared with non-orphanhood over 11 survey rounds between 2001 and 2018. Controlling for community HIV prevalence, household socioeconomic status, and adolescent age, we examined the association between community prevalence of ART use among people living with HIV and prevalence of male circumcision, including traditional circumcision. The primary outcome was orphanhood among adolescents aged 15-19 years. Orphanhood declined from 52% (920 of 1768 participants) in 2001-02 to 23% (592 of 2609 participants) by 2016-18 (p<0·0001), while double orphanhood declined from 20% (346 of 1768 participants) to 3% (86 of 2609 participants) (p<0·0001). Community prevalence of ART use among people living with HIV increased from 11% (105 of 945 participants) in 2005-06 to 78% (1163 of 1485 participants) in 2016-18. Male circumcision rates rose from 19% (147 of 790 participants) in 2005-06 to 65% (3535 of 5433 participants) in 2016-18. In the multinomial logistic regression model, a 10% increase in community prevalence of ART use was associated with a decrease in maternal orphanhood (adjusted relative RR 0·90, 95% CI 0·85-0·95) and double orphanhood (0·80, 0·75-0·85). In the post-ART era, a 10% increase in the community prevalence of male circumcision was associated with a decrease in paternal orphanhood (2005-18, adjusted relative RR 0·92, 0·87-0·97) and double orphanhood (0·91, 0·85-0·98). Widespread availability and uptake of HIV combination prevention was associated with marked reductions in orphanhood among adolescents. Reductions in orphanhood promise improved health and social outcomes for young people. Eunice Kennedy Shriver National Institute of Child Health and Human Development, the National Institute of Allergy and Infectious Diseases, the National Institute of Mental Health, and the Division of Intramural Research of the National Institute for Allergy and Infectious Diseases.


[Therapeutic targets in Gaucher's disease].
Gaucher's disease (GD) occurs because of deficiency of the enzyme beta-glucocerebrosidase that results in accumulation of this glycolipid compound in the cells of the macrophage-monocyte system. There are 3 types: type 1 is non-neuronopathic with primarily visceral signs and symptoms which range tremendously in severity; infantile-onset type 2 and later-onset type 3 involve the central nervous system. More than 300 mutations have been described in the gene, partially explaining phenotypic heterogeneity. Commercialization in 1991 of the first enzyme replacement therapy, alglucerase, resulted in a revolution in the management of patients with symptomatic GD (i.e., by improving the hematological and visceral signs and symptoms). Within the first 5 years of alglucerase, its safety and efficacy in improving hemoglobin levels and platelet counts, and in reducing splenic and hepatic enlargement were confirmed albeit recognizing its inability to impact neurological symptoms and signs because of its large molecular size. Recombinant imiglucerase soon replaced alglucerase as the standard of care for GD. The therapeutic targets recently defined as treatment goals were: normalization of cell counts; reduction of liver and spleen volume; elimination of the infiltration in the bone marrow to prevent the complications, and improvement in surrogate biomarkers.


The montreal cognitive assessment and mini-mental state examination visuoexecutive subtests in acute ischemic stroke patients and their correlations with demographic and clinical factors.
Visuoexecutive impairment is common among acute ischemic stroke patients. This study aimed to examine the ability of the Montreal Cognitive Assessment (MoCA) and Mini-Mental State Examination (MMSE) visuoexecutive subtests to detect visuoexecutive abnormality in acute ischemic stroke patients and to identify the predictors for their impairments. 336 patients who completed the MMSE and MoCA were enrolled in this study. We compared the proportion of participants with incorrect MoCA visuoexecutive tasks and MMSE pentagon copying. Multivariate logistic regression analysis was used to evaluate the associations between the visuoexecutive dysfunction and demographic and clinical characteristics in the samples. Among all the participants, the MoCA detected more visuoexecutive dysfunction than the MMSE (88.69% vs. 45.83%, respectively; p < 0.001). The predictors identified by the univariate analysis included the factors of gender, age, educational level, smoking, alcohol consumption, Oxfordshire Community Stroke Project (OCSP), previous strokes, initial NIHSS score and number of old lacunar infarctions, while from the multivariate logistic regression analysis, the factors of age, educational level, NIHSS score, previous strokes and number of old lacunar infarctions served as predictive factors for the visuoexecutive impairment in acute stroke patients. In conclusion, visuoexecutive impairment is associated with the factors of the educational level, stroke severity, stroke history and number of old lacunar infarctions. Our findings may guide the clinicians to intervene the risks for the patients at an early stage after stroke and form the basis for good rehabilitation plans.


Adiabatic inversion pulses for myocardial T1 mapping.
To evaluate the error in T1 estimates using inversion-recovery-based T1 mapping due to imperfect inversion and to perform a systematic study of adiabatic inversion pulse designs in order to maximize inversion efficiency for values of transverse relaxation (T2) in the myocardium subject to a peak power constraint. The inversion factor for hyperbolic secant and tangent/hyperbolic tangent adiabatic full passage waveforms was calculated using Bloch equations. A brute-force search was conducted for design parameters: pulse duration, frequency range, shape parameters, and peak amplitude. A design was selected that maximized the inversion factor over a specified range of amplitude and off-resonance and validated using phantom measurements. Empirical correction for imperfect inversion was performed. The tangent/hyperbolic tangent adiabatic pulse was found to outperform hyperbolic secant designs and achieve an inversion factor of 0.96 within ±150 Hz over 25% amplitude range with 14.7 µT peak amplitude. T1 mapping errors of the selected design due to imperfect inversion was ∼4% and could be corrected to <1%. Nonideal inversion leads to significant errors in inversion-recovery-based T1 mapping. The inversion efficiency of adiabatic pulses is sensitive to transverse relaxation. The tangent/hyperbolic tangent design achieved the best performance subject to the peak amplitude constraint.


Molecular taxonomy of a new potyvirus isolated from chilli pepper in Thailand.
A virus isolated from chilli pepper plants in Kamphaengsaen, Nakorn Pathom, showing vein banding mottle symptoms was classified using sequence analysis and phylogeny of the coat protein gene and 3' noncoding region (3'NCR). This virus was found to be a typical potyvirus on the basis of particle morphology, biological properties and cytopathology. The 3'terminus region of the genome of 1,309 nucleotides, representing the viral coat protein gene and 3' NCR was cloned and sequenced. Nucleotide sequence analysis indicated that the 3' region of the viral genome had a poly A tail of at least 12 nucleotides, a noncoding region of 272 nucleotides, a coat protein gene of 864 nucleotides and 161 nucleotides representing the 3' terminus of the polymerase gene. The amino acid sequence of the coat protein was compared with those of 23 distinct potyviruses, and 63.1% shown to be the highest homology. However the 3' NCR had, at most, 29.7% random homology, thus indicating that this virus is a distinct species in the genus Potyvirus in the family Potyviridae. The result is well supported by previous studies on the biology and biochemical properties of this virus.


Lipid storage myopathy with normal carnitine levels.
A 28-year-old female, who showed a floppy baby syndrome during early infancy, had a non-progressive proximal muscle weakness with easy fatiguability since childhood. Two muscle specimens biopsied at the age of 28 years revealed myriads of 1-3-mum wide abnormal spaces containing neutral fat in type I and type II fibers. Both biopsies demonstrated a type I fiber preponderance. Electron microscopy demonstrated lipid excess and normal mitochondria by simple inspection. The mitochondrial area and sarcotubular membrane profile concentration in morphometry of longitudinal sections were also normal. Cross-sections, however, revealed a slight decrease of the individual mitochondrial size and of the sarcotubular membrane profile concentration . Serum and muscle carnitine levels and the muscle carnitine palmityltransferase level were all within normal range. Besides carnitine deficiency other biochemical defects can occur in lipid storage myopathy, which represents a syndrome rather than a unique disease entity.