[Significance of the position of the endoprosthesis acetabular cup from the biomechanical and clinical viewpoint--recommendations for a classification].
The success of an artificial joint replacement over the long term depends, for the most part, on the optimal positioning of the acetabular cup. We investigated this thought in terms of biomechanical and clinical considerations, and, on the basis of a proposed classification, attempted to ascertain the best possible position. On the basis of our analysis we determined that the ideal position is an angle of 35 degrees, with a tolerance range of 25 degrees to 45 degrees. Here, the load on the polyethylene is low, so that wear and the formation of particles are minimized. This position can readily be achieved surgically with the aid of an auxiliary device and clinically provides the best results in terms of muscular stability, endurance and optimal scoring.


Effects of gadolinium chelate on the evolution of the nanoscale structure in peptide hydrogels.
Small-angle X-ray scattering (SAXS) was used to monitor peptide hydrogelation with and without the MRI contrast agent gadolinium chelate (Gd(III)-chelate). The gelators are a pair of decapeptides that are self-repulsive but mutually attractive. Gd(III)-chelate was either free or covalently bound to one of the decapeptides. Free and conjugated Gd(III)-chelate have the opposite effects on peptide gelation: free Gd(III)-chelate slows down gelation while having little effect on the cross-sectional area of peptide fibers; covalently conjugated Gd(III)-chelate speeds up gelation and results in peptide fibers with significantly greater cross-sectional area. After 24 h of gelation, the cross-sectional areas of hydrogels with no Gd(III)-chelate, with free Gd(III)-chelate and with conjugated Gd(III) chelate are 3700, 3800, and 6300 Å(2), respectively. Free Gd(III)-chelate is not incorporated into peptide fibers and remains in solution with little effect on MRI intensity upon gelation. In contrast, covalently conjugated Gd(III)-chelate is not only incorporated into peptide fibers, but further aggregates toward the center of the peptide fibers. In conclusion, to visualize hydrogelation using (1)H MRI, it is necessary to conjugate Gd(III)-chelate to the material covalently and use T(2)-weighted imaging.


Psychosocial Interventions for Alcohol and/or Drug Misuse and Use Disorders in Women: A Systematic Review.
Background: Although men and women who misuse substances have different needs, no rigorous systematic literature review has been conducted examining psychosocial substance use interventions for women across a broad range of types of therapeutic approaches and populations. Materials and Methods: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were used to guide this review. English language, peer-reviewed research articles indexed in PubMed, PsycINFO, CINAHL Complete, and Web of Science through May 6, 2021, were searched. Peer-reviewed articles were included in the review if they were written in English; described a randomized controlled trial of a psychosocial intervention to reduce substance misuse and related problems in women; and reported quantitative data on alcohol or illicit drug use as an outcome that was linked to the interventions. Results: A total of 51 articles met eligibility criteria, reflecting a broad array of interventions with different levels of methodological rigor. Several, but not most, interventions were tailored to meet the needs of specific subgroups of women, but evidence regarding the efficacy of tailoring was inconclusive. Overall, 61% of studies reported one or more positive substance-related intervention effects, with target substance (alcohol only vs. other drugs only or both alcohol and other drugs) and intervention dosage associated with intervention success. Conclusions: Fewer studies targeting alcohol only reported one or more positive intervention outcomes. This warrants further study, given that polysubstance use is the norm, not the exception. Future research might also focus on reducing treatment barriers to women, as this has the potential to improve overall treatment outcomes for this population.


Analysis of the MIR396 gene family and the role of MIR396b in regulating fiber length in cotton.
Cotton fiber is one of the most important natural raw materials in the world textile industry. Improving fiber yield and quality has always been the main goal. MicroRNAs, as typical small noncoding RNAs, could affect fiber length during different stages of fiber development. Based on differentially expressed microRNA in the two interspecific backcross inbred lines (BILs) with a significant difference in fiber length, we identified the miR396 gene family in the two tetraploid cotton genomes and found MIR396b_D13 as the functional precursor to produce mature miR396 during the fiber elongation stage. Among 46 target genes regulated by miR396b, the GROWTH-REGULATING FACTOR 5 gene (GRF5, Gh_A10G0492) had a differential expression level in the two BILs during fiber elongation stage. The expression patterns indicated that the miR396b-GRF5 regulatory module has a critical role in fiber development. Furthermore, virus-induced gene silencing (VIGS) of miR396b significantly produced longer fiber than the wild type, and the expression level of GRF5 showed the reverse trends of the miR396b expression level. The analysis of co-expression network for the GRF5 gene suggested that a cytochrome P450 gene functions as an allene oxide synthase (Gh_D06G0089, AOS), which plays a critical role in jasmonate biosynthetic pathway. In conclusion, our results revealed that the miR396b-GRF5 module has a critical role in fiber development. These findings provide a molecular foundation for fiber quality improvement in the future.


Some Perspectives on Hypersensitivity to Coronary Stents.
The development of coronary stents has represented a revolution in the treatment of coronary heart disease. Beyond their many advantages, stents also have their limitations and complications. Allergic reactions to coronary stents are more common than acknowledged. These stented patients are exposed to foreign substances inserted in direct contact with the coronary intima. Hypersensitivity to stent components and drugs prescribed after stent insertion together with any environmental exposure seem to contribute to these adverse reactions. Patients can present to the hospital with a wide range of symptoms and multiple complications, the most important ones being instent restenosis and stent thrombosis. Although not very common (and not always easy to identify), allergic reactions after coronary or peripheral stents should be taken into account. Careful selection of patients (for elective stent implantation) depending on the propensity to allergies, although hard to achieve, represents a key factor in reducing the number of these complications.


Oxidized messenger RNA induces translation errors.
To investigate the effect of RNA oxidation on normal cellular functions, we studied the translation of nonoxidized and oxidized luciferase mRNA in both rabbit reticulocyte lysate and human HEK293 cells. When HEK293 cells transfected with nonoxidized mRNA encoding the firefly luciferase protein were cultured in the presence of paraquat, there was a paraquat concentration-dependent increase in the formation of luciferase short polypeptides (SPs) concomitant with an increase in 8-oxoguanosine. Short polypeptides were also formed when the mRNA was oxidized in vitro by the Fe-ascorbate-H(2)O(2) metal-catalyzed oxidation system before its transfection into cells. Translation of the in vitro oxidized mRNA in rabbit reticulocyte lysate also led to formation of SPs. The SPs formed by either procedure contained the N-terminal and the C-terminal portions of the tagged luciferase. In addition, the oxidized mRNA was able to associate with ribosomes to form polysomes similar to those formed with nonoxidized mRNA preparations, indicating that the oxidized mRNAs are mostly intact; however, their translation fidelity was significantly reduced. Nevertheless, our results indicate that the SPs were derived from both premature termination of the translation process of the oxidized mRNA and the proteolytic degradation of the modified full-length luciferase resulting from translation errors induced by oxidized mRNA. In light of these findings, the physiological consequences of mRNA oxidation are discussed.


A framework for simplification of quantitative systems pharmacology models in clinical pharmacology.
Quantitative systems pharmacology (QSP) is a relatively new discipline within modelling and simulation that has gained wide attention over the past few years. The application of QSP models spans drug-target identification and validation, through all drug development phases as well as clinical applications. Due to their detailed mechanistic nature, QSP models are capable of extrapolating knowledge to predict outcomes in scenarios that have not been tested experimentally, making them an important resource in experimental and clinical pharmacology. However, these models are complicated to work with due to their size and inherent complexity. This makes many applications of QSP models for simulation, parameter estimation and trial design computationally intractable. A number of techniques have been developed to simplify QSP models into smaller models that are more amenable to further analyses while retaining their accurate predictive capabilities. Different simplification techniques have different strengths and weaknesses and hence different utilities. Understanding the utilities of different methods is essential for selection of the best method for a particular situation. In this paper, we have created an overall framework for model simplification techniques that allows a natural categorisation of methods based on their utility. We provide a brief description of the concept underpinning the different methods and example applications. A summary of the utilities of methods is intended to provide a guide to modellers in their model endeavours to simplify these complicated models.


Detecting malingered memory deficits with the Recognition Memory Test.
The purpose of the present study was to examine the efficacy of using the Recognition Memory Test (RMT) as a marker for malingered memory deficits. Data from 60 subjects, including 40 patients seen for neuropsychological evaluation and 20 university undergraduates, are reported. The university students were given experimental instructions to malinger. Students were compared to 20 memory-impaired and 20 memory-nonimpaired patients. The students who were instructed to malinger memory impairment performed more poorly than both groups of patients. Discriminant function analyses using the two scores derived from the RMT as predictors of group membership resulted in a 100% initial correct classification rate and a 96.7% correct classification rate on cross-validation.


Duodenal perforation with an inferior vena cava filter: an unusual cause of abdominal pain.
The insertion of inferior vena cava (IVC) filters results in device migration at rates that exceed 50% in some studies, although the clinical significance of migration remains in question. These filters can also erode or penetrate the IVC wall, injuring adjacent retroperitoneal and abdominal structures. The risk of erosion or perforation is estimated to be as much as 25%, although clinical symptoms are observed far less frequently in patients with these complications. We describe the presentation, evaluation, and treatment of a patient with an IVC strut protruding into the duodenum. This case report discusses complications, presenting symptoms, and treatment of patients with IVC filters complications.


SdiA Improves the Acid Tolerance of E. coli by Regulating GadW and GadY Expression.
The acid tolerance mechanism is important for Escherichia coli to resist acidic conditions encountered in mammalian host digestive tract environment. Here, we explored how the LuxR protein SdiA influenced E. coli acid tolerance ability in the context of the glutamate- and glutamine-dependent acid resistance system (AR2). First, using a growth and acid shock assay under different acid stresses, we demonstrated that the deletion of sdiA in SM10λpir or BW25113 led to impaired growth under the acidic environment of pH 3-6, which was restored by complementary expression of SdiA. Next, transcriptome sequencing and qPCR disclosed that the expression of glutamate decarboxylase W (GadW) and GadY, the key members of the AR2 system, were regulated by SdiA. Further, β-galactosidase reporter assays showed that the promoter activity of gadW and gadY was positively regulated by SdiA. Moreover, qPCR and β-galactosidase reporter assays confirmed that the regulation of SdiA on GadW, but not GadY, could be enhanced by quorum sensing (QS) signal molecules AHLs. Collectively, these data suggest that SdiA plays a crucial role in acid tolerance regulation of E. coli. Our findings provide new insights into the important contribution of quorum sensing system AHLs-SdiA to the networks that regulate acid tolerance.


[Neutropenia induced by taxoids and its control with granulocyte colony-stimulating factor].
Nowadays, the use of taxoid derivated compounds constitutes one of the main chemotherapeutic weapons against breast cancer, ovarian cancer and non-microcytic lung cancer. The limiting factor when determining the dose of taxoids to be administered is the occurrence of neutropenia which is a common side-effect of this therapy. That is why we propose this retrospective study in which we assessed docetaxel and paclitaxel induced neutropenia in oncologic patients by means of colony stimulating factors consumption. A systematic revision of filgastrin consumption by patients treated with taxoids during 2003 in the Infanta Cristina Hospital (Badajoz, Spain) was performed. Filgastrin consumption data were obtained individually, considering its dispensation to external patients as well as the possible administration during hospital stay. 22 out of the 140 patients treated with paclitaxel required colony stimulating factor. On the other hand, 27 out of 116 patients treated with docetaxel received filgastrin. The relation between filgastrin (micrograms) and taxoid consumption (milligrams) was 1.35 for paclitaxel and 4.17 for docetaxel. Taking into account each patient taxoids consumption (milligrams), the results were 7.09 for paclitaxel and 20.12 for docetaxel. When selecting the patients who suffer from breast cancer and lung cancer, these ratios were 0.76 for paclitaxel and 6.48 for docetaxel. The docetaxel group consumed 2.83 more colony stimulating factor than the pacitaxel group. This ratio was even greater (3.1) when ovarian cancer patients were excluded. These results showed an unfavorable relation for docetaxel, thus confirming that the use of docetaxel provokes a greater incidence and severity of neutropenia.


Mothers' ranking of clinical intervention strategies used to promote infant health.
To support evidence-based practice for infant health promotion by determining mothers' preferences among eight clinical intervention strategies. A sample of 138 mothers of 4-month-old infants who received care through a county health department used a card sort method to rank order intervention strategies and identified advantages and disadvantages of each method. The mothers' rank ordering of the clinical intervention strategies, beginning with the most preferred, was: 1. Nurse home visitation; 2. Group session with mothers, led by a nurse; 3. Community lay worker home visitation; 4. Classes in the clinic; 5. Health diary; 6. Videotapes at home; 7. Brochures; and 8. Videotapes in the clinic. Intervention strategies that use interpersonal communication, including the opportunity for mothers to ask questions, were most preferred. Strategies that involve one-way messages to mothers were least preferred. Investment in strategies that do not appeal to mothers are likely be ineffective in promoting infant health and wasteful of health care dollars.


The steroid receptor superfamily--American Association for Cancer Research special conference. 8-12 January 1999, Indian Wells, California, USA.
The meeting dealt with transcriptional regulation by nuclear receptors, their role in development and animal physiology and their exploitation as targets for therapeutic intervention. The field is at a stage where it is possible to address many different issues relevant to hormone action, ranging from the structure of nuclear receptors to the biological roles of individual components and so, despite the number of meetings devoted to these topics, this AACR meeting was considered a great success. In addition, a number of other transcriptional systems in yeast and Drosophila, as well as in vertebrates, were presented, which illustrated the extent to which the transcription machinery is conserved throughout the animal kingdom. Thus, although yeast does not immediately strike one as being a particularly good model system for studying endocrinology, it does in fact rely on transcriptional apparatus that is remarkably similar to the mammalian counterpart. Nevertheless, while presentation of this basic research added to the interest of the meeting, this report will focus on receptors themselves and on topics with most relevance to clinical therapy.


Effect of routine bedside procedures on intracranial pressure.
The effect on intracranial pressure (ICP) of routine bedside procedures, such as changing the patient's position, suction, rotation, flexion or extension of the head, was investigated in 21 comatose patients with brain edema. Simple maneuvers, which under physiological conditions have no effect on ICP, often led to significant changes in the ICP in these patients. It is suggested that monitoring of ICP and adjustment of body position in accordance with the level of ICP become a standard procedure in neurosurgical wards.


Carbohydrate structure characterization by tandem ion mobility mass spectrometry (IMMS)2.
A high resolution ion mobility spectrometer was interfaced to a Synapt G2 high definition mass spectrometer (HDMS) to produce IMMS-IMMS analysis. The hybrid instrument contained an electrospray ionization source, two ion gates, an ambient pressure linear ion mobility drift tube, a quadrupole mass filter, a traveling wave ion mobility spectrometer (TWIMS), and a time-of-flight mass spectrometer. The dual gate drift tube ion mobility spectrometer (DTIMS) could be used to acquire traditional IMS spectra but also could selectively transfer specific mobility selected precursor ions to the Synapt G2 HDMS for mass filtration (quadrupole). The mobility and mass selected ions could then be introduced into a collision cell for fragmentation followed by mobility separation of the fragment ions with the traveling wave ion mobility spectrometer. These mobility separated fragment ions are finally mass analyzed using a time-of-flight mass spectrometer. This results in an IMMS-IMMS analysis and provides a method to evaluate the isomeric heterogeneity of precursor ions by both DTIMS and TWIMS to acquire a mobility-selected and mass-filtered fragmentation pattern and to additionally obtain traveling wave ion mobility spectra of the corresponding product ions. This new IMMS(2) instrument enables the structural diversity of carbohydrates to be studied in greater detail. The physical separation of isomeric oligosaccharide mixtures was achieved by both DTIMS and TWIMS, with DTIMS demonstrating higher resolving power (70-80) than TWIMS (30-40). Mobility selected MS/MS spectra were obtained, and TWIMS evaluation of product ions showed that isomeric forms of fragment ions existed for identical m/z values.


A new acylated flavonol glycoside from the aerial parts of Cardamine tangutorum.
A new acylated flavonol glycoside, kaempferol-3-O-β-D-(2-feruloylglucopyranosyl) (1 → 6)-[β-D-glucopyranosyl(1 → 2)]-β-D-glucopyranoside, named tangutorumoside A (1), together with 12 known compounds, was isolated from 50% acetone extract of Cardamine tangutorum. Their structures were elucidated by NMR and MS experiments. In addition, compound 1 could promote the proliferation of splenic lymphocytes and thymic lymphocytes with ConA in vitro.


Development and validation of the childhood narcissism scale.
In this article, we describe the development and validation of a short (10 item) but comprehensive self-report measure of childhood narcissism. The Childhood Narcissism Scale (CNS) is a 1-dimensional measure of stable individual differences in childhood narcissism with strong internal consistency reliability (Studies 1-4). The CNS is virtually unrelated to conventional measures of self-esteem but is positively related to self-appraised superiority, social evaluative concern and self-esteem contingency, agentic interpersonal goals, and emotional extremity (Study 5). Furthermore, the CNS is negatively related to empathic concern and positively related to aggression following ego threat (Study 6). These results suggest that childhood narcissism has similar psychological and interpersonal correlates as adult narcissism. The CNS provides researchers a convenient tool for measuring narcissism in children and young adolescents with strong preliminary psychometric characteristics.


A Computed Tomography Nomogram for Assessing the Malignancy Risk of Focal Liver Lesions in Patients With Cirrhosis: A Preliminary Study.
The detection and characterization of focal liver lesions (FLLs) in patients with cirrhosis is challenging. Accurate information about FLLs is key to their management, which can range from conservative methods to surgical excision. We sought to develop a nomogram that incorporates clinical risk factors, blood indicators, and enhanced computed tomography (CT) imaging findings to predict the nature of FLLs in cirrhotic livers. A total of 348 surgically confirmed FLLs were included. CT findings and clinical data were assessed. All factors with P < 0.05 in univariate analysis were included in multivariate analysis. ROC analysis was performed, and a nomogram was constructed based on the multivariate logistic regression analysis results. The FLLs were either benign (n = 79) or malignant (n = 269). Logistic regression evaluated independent factors that positively affected malignancy. AFP (OR = 10.547), arterial phase hyperenhancement (APHE) (OR = 740.876), washout (OR = 0.028), satellite lesions (OR = 15.164), ascites (OR = 156.241), and nodule-in-nodule architecture (OR =27.401) were independent predictors of malignancy. The combined predictors had excellent performance in differentiating benign and malignant lesions, with an AUC of 0.959, a sensitivity of 95.24%, and a specificity of 87.5% in the training cohort and AUC of 0.981, sensitivity of 94.74%, and specificity of 93.33% in the test cohort. The C-index was 96.80%, and calibration curves showed good agreement between the nomogram predictions and the actual data. The nomogram showed excellent discrimination and calibration for malignancy risk prediction, and it may aid in making FLLs treatment decisions.


[Image processing in radiology].
Medical imaging processing and analysis methods have significantly improved during recent years and are now being increasingly used in clinical applications. Preprocessing algorithms are used to influence image contrast and noise. Three-dimensional visualization techniques including volume rendering and virtual endoscopy are increasingly available to evaluate sectional imaging data sets. Registration techniques have been developed to merge different examination modalities. Structures of interest can be extracted from the image data sets by various segmentation methods. Segmented structures are used for automated quantification analysis as well as for three-dimensional therapy planning, simulation and intervention guidance, including medical modelling, virtual reality environments, surgical robots and navigation systems. These newly developed methods require specialized skills for the production and postprocessing of radiological imaging data as well as new definitions of the roles of the traditional specialties. The aim of this article is to give an overview of the state-of-the-art of medical imaging processing methods, practical implications for the radiologist's daily work and future aspects.


The Crotalaria juncea metal transporter CjNRAMP1 has a high Fe uptake activity, even in an environment with high Cd contamination.
Large quantities of Fe and Cd accumulate in the leaves of the metal-accumulating leguminous plant, Crotalaria juncea. A member of the metal transporter NRAMP family was cloned from C. juncea. The amino acid sequence of this clone, designated CjNRAMP1, was similar to the sequence of Arabidopsis AtNRAMP1, which is involved in Fe and Cd transport. Organ-specific analysis showed that CjNRAMP1 mRNA was expressed mainly in the leaves of C. juncea plants, as well as in stems and roots. Use of green fluorescent protein fused to CjNRAMP1 suggested its localization to the plasma membranes of plant cells. Complementation experiments using yeast strains with impaired metal transport systems showed that CjNRAMP1 transported both Fe and Cd in an inward direction within the cells. Transgenic Arabidopsis plants overexpressing CjNRAMP1 showed high tolerance to Cd, with Cd translocation from roots to leaves being substantially greater in transgenic than in wild-type plants. Overexpression of CjNRAMP1 resulted in a greater accumulation of Fe in shoots and roots, suggesting that CjNRAMP1 recognizes Fe and Cd as substrates and that the high Cd tolerance of CjNRAMP1 is due to its strong Fe uptake activity, even in the presence of high Cd concentrations in the rhizosphere.


Infection of percutaneous devices: prevention, monitoring, and treatment.
Infection continues to pose the major obstacle to long-term percutaneous access. Development of methods to prevent infection or techniques to determine early onset of infection at a time when antibiotic therapy may prove successful would be of enormous value. Our laboratory has been working toward developing and testing a noninvasive semiquantitative swab culture technique (SQ) to monitor percutaneous leads for infection. This technique was found to have a 76% sensitivity having identified 47 of 62 organisms detected by a quantitative tissue culture technique (Q) at the time of system explant. Furthermore, 47 of 61 organisms identified by the SQ technique accurately detected those isolated by the Q techniques. Accordingly, the SQ technique has a 77% specificity. This technique was capable of detecting organisms a median of 14 days prior to overt clinical infection. Prompt initiation of oral antibiotic treatment based on SQ results has doubled system survival compared with untreated systems. Clearly, the SQ technique has proven useful to monitoring percutaneous devices.


Knowledge, attitudes, and practices of registered dietitians and nutritionists regarding enteral and parenteral nutrition support in Ghana: a needs assessment study.
There is a paucity of data on enteral and parenteral (EN and PN) nutrition support (NS) provided by nutrition and dietetic practitioners in adult acute care settings in Ghana. Furthermore, gray literature suggests that Ghanaian clinical nutrition professionals (CNPs) are seldom involved in advanced nutrition care teams. To assess the knowledge, attitudes, and practices of Ghanaian CNPs regarding EN and PN. An online cross-sectional survey was administered to Ghanaian CNPs ahead of a professional development workshop on EN and PN Support. Participants were asked questions about initiation and timing of NS, and knowledge on availability of commercial formula. A 5-point Likert scale was used to assess self-efficacy in using EN and PN. To assess practical knowledge on EN and PN, participants were asked to identify whether EN or PN was indicated for seven short case scenarios. Open-ended questions were used to assess reasons for participant self-ratings. A total of 76 dietitians, nutritionists, students, and interns completed the survey. For EN, self-efficacy scores were lowest for the calculation of enteral goal rate, and goal volume (mean 3.20 ± 1.27), and writing of EN prescriptions (mean 3.07 ± 1.29). Self-efficacy scores for the formulation of alternative formulas in lieu of commercial formula were the highest (3.63 ± 1.36). For PN, self-efficacy scores for all domains were lower than 3, with the lowest scores observed for writing PN prescriptions (2.19 ± 1.14) and determining micronutrient additives (2.12 ± 1.04). We identified limited training and lack of practical exposure to NS, limited ability to effectively monitor tube feeds, and prohibitive cost and limited availability of EN and PN formula among the barriers impacting self-efficacy scores. Given the vital role that CNPs play in the delivery of EN and PN, it is important to develop professional training programs especially focused on PN to bridge knowledge and practice gaps.


Velocity and stability of solitary planar travelling wave solutions of intracellular [Ca]2+.
Normal cardiac muscle contraction occurs in response to a rapid rise followed by a slower decay in intracellular calcium concentration. When cardiac muscle cells are loaded with calcium, an intracellular store releases calcium into the cytosol by the process of calcium-induced calcium release (CICR). This release contributes to the rise in intracellular calcium which in turn triggers contraction. We use two qualitative piecewise linear reaction-diffusion models of this behaviour to investigate the speed, stability and waveform of plane waves using singular perturbation techniques.


[Sequential high-dose cytarabine therapy in combination with asparaginase in acute myeloid leukemia].
Between 1984 and 1987 14 patients with acute non-lymphocytic leukemia were treated with sequential high-dose cytosine arabinoside in combination with asparaginase. Twelve patients were suffering from refractory leukemia; in these patients complete remissions were achieved in 58%. The efficacy of this schedule was much better in patients with substantial leukemia cell reduction due to antecedent conventional therapy and no more than 25% blast cells in the bone marrow. In this subgroup complete remissions were achieved in 75% and 86% respectively, taking into account only the completed treatment courses. Beside the well-known side-effects such as alopecia, nausea, vomiting and hepatotoxicity, we observed an increase in severe infections. Three patients died of pulmonary mycosis.


Common VDR polymorphisms and idiopathic short stature in children from northern Greece.
A Vitamin D Receptor gene (VDR) polymorphism, rs10735810 (Fok1), has been associated in the past with idiopathic short stature (ISS) in a linkage study. We have investigated the association of the same, as well as a different polymorphism in the same gene [rs731236 (Taq1)] with ISS, in an independent study in Greek children. The VDR rs10735810 (Fok1) and rs731236 (Taq1) polymorphisms were genotyped in a group of ISS children (n= 47) and an age and sex-matched group of normal height children (n= 60) from northern Greece. Genotyping was accomplished through established PCR-RFLP methods. An association trend of rs10735810 with ISS was observed, with the TT (ff) genotype being apparently underrepresented among ISS children compared to controls (p= 0.076; OR= 0.165, 95% CI= 0.025-1.094). The above results, together with recent evidence related to the functionality of the rs10735810 polymorphism, cannot exclude an involvement of VDR in the pathogenesis of ISS. Hippokratia 2015, 19 (1): 25-29.


Robust and electron-rich cis-palladium(II) complexes with phosphine and carbene ligands as catalytic precursors in Suzuki coupling reactions.
A new imidazolinium ligand precursor [L(2)H]Cl (2) was prepared in 86 % yield. Compared with its imidazolium counterpart, [L(1)H]Cl (1), 2 is very sensitive to moisture and can undergo ring-opening reactions very readily. Palladium complexes with the ring-opened products from imidazolinium salts were isolated and characterized by X-ray crystallography. Theoretical studies confirmed that the imidazolinium salt has a higher propensity for the ring-opening reaction than the imidazolium counterpart. New mixed phosphine/carbene palladium complexes, cis-[PdCl(2)(L)(PR(3))] (L=L(1) and L(2); R=Ph, Cy), were successfully prepared. These complexes are highly robust as revealed by variable-temperature NMR spectroscopic studies and thermal gravimetric analysis. The structural and electronic properties of the new complexes on varying the carbene group (imidazol-2-ylidene group (unsaturated carbene) vs. imidazolin-2-ylidene (saturated carbene)) and the phosphine group (PPh(3) vs. PCy(3)) were studied in detail by X-ray crystallography, X-ray photoelectron spectroscopy, and theoretical calculations. The catalytic study reveals that cis-[PdCl(2)(L(2))(PCy(3))] is a competent Pd(II) precatalyst for Suzuki coupling reactions, in which unreactive aryl chlorides can be applied as substrates.


Contraceptive drug, Nestorone, enhances stem cell-mediated remodeling of the stroke brain by dampening inflammation and rescuing mitochondria.
Ischemic stroke remains a significant unmet need causing massive mortality and morbidity due to few treatment options with limited therapeutic window. The progestin Nestorone® (segesterone acetate) displays high affinity for the progesterone receptor in exerting its potent birth control and hormone replacement therapy. Accumulating evidence implicates a new utility of Nestorone in affording neuroprotection in a variety of central nervous system diseases, including stroke. However, the mechanism of action mediating Nestorone's neuroprotection in stroke remains unknown. Here, we showed that stand-alone treatments of Nestorone or human amniotic fluid-derived stem cells (hAFSc), but more pronounced with their combined treatment, led to significant improvements in behavioral function and reductions in infarction and peri-infarct cell loss in adult rats with ischemic stroke. We detected significantly lower levels of pro-inflammatory signals (OX6 and IBA1) coupled with enhanced levels of stem cell proliferation (Ki67) and differentiation (DCX and MAP2) in both brain and spleen of stroke rats that received stand-alone or combined treatments of Nestorone and hAFSc. In concert, the in vitro oxygen-glucose deprivation stroke model revealed that neural stem cells treated with Nestorone exhibited increased stem cell proliferation and differentiation that was accompanied by rescue of the mitochondrial respiratory activity characterized by reduced mitochondrial reactive oxygen species, increased ATP, elevated mitochondrial deacetylase Sirtuin 3 (SIRT3), and a normalized ratio of acetyl-superoxide dismutase 2 (Ac-SOD2)/SOD2, suggesting the key role of mitochondrial metabolism and oxidative protection in Nestorone's therapeutic effects in stroke.


An addiction-based mobile health weight loss intervention: protocol of a randomized controlled trial.
The notion of obesity as an addictive process is controversial. However, studies show that between 5.9 and 30.7% of adolescents with obesity report food or eating addiction. Few weight management interventions have tested techniques based on addiction medicine principles. This multi-center randomized control trial (RCT) is designed to test the effectiveness of a mobile health (mHealth) weight-loss intervention based on addiction principles, such as withdrawal and tolerance, in a sample of 180 adolescents (ages 14-18) recruited from four pediatric weight management clinics in Southern California. Akin to a Multiphase Optimization Strategy (MOST) design evaluating multicomponent behavioral interventions, we will compare the combination of an app + phone coaching (App+Coach) to app alone (App) and in-clinic multi-disciplinary (Clinic) intervention arms. The primary outcome is mean change in zBMI and %BMIp95 over 18 months. We hypothesize that youth who receive App+Coach will have a greater reduction in body weight over the 18-month study period at a lower cost than standard of care models. Secondary outcomes include adherence to treatment regimen, intervention satisfaction, effect of the intervention on metabolic factors and activity level. We will also explore potential moderators of intervention effectiveness such as addictive eating habits, self-regulation and executive functioning. New and creative approaches are needed to address pediatric obesity. If successful, this RCT may provide an innovative and cost-effective mHealth approach, based on addiction methods, for weight loss among adolescents with overweight and obesity.


Wet electron microscopy with quantum dots.
Wet electron microscopy (EM) is a new imaging method with the potential to allow higher spatial resolution of samples. In contrast to most EM methods, it requires little time to perform and does not require complicated equipment or difficult steps. We used this method on a common murine macrophage cell line, IC-21, in combination with various stains and preparations, to collect high resolution images of the actin cytoskeleton. Most importantly, we demonstrated the use of quantum dots in conjunction with this technique to perform light/electron correlation microscopy. We found that wet EM is a useful tool that fits into a niche between the simplicity of light microscopy and the high spatial resolution of EM.


[A Case Report of Resectable Leiomyosarcoma of the Duodenum Origin Invading to the Inferior Vena Cava].
A 40's woman had a complaint of abdominal and back pain. Enhanced CT visualized a large retroperitoneal tumor and huge multiple myomas of the uterus. The tumor was 10cm in diameter and located in the anterior of the inferior vena cava, and progressed from the posterior of the duodenum to the abdominal aortic bifurcation. Diffusion-weighted MR image showed the tumor with high signal intensity. Upper gastrointestinal endoscopy revealed a type 2 tumor at the anal side of the Vater. The patient was performed curativly abdominal total hysterectomy and pancreaticoduodenectomy with inferior vena cava resection. Immunohistochemical examination showed that the tumor cells were negative for CD34 and c-kit, and positive for desmin and a-SMA. The tumor was histopathologically diagnosed as leiomyosarcoma originating from the duodenum.


The safety of treatments for angioedema with hereditary C1 inhibitor deficiency.
Angioedema is a localized and self-limiting edema of the subcutaneous and submucosal tissue. Hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) is the best characterized form of hereditary angioedema. In C1-INH-HAE, the reduced plasma levels of C1-INH cause instability of the contact system with release of bradykinin, the key mediator of angioedema. C1-INH-HAE is characterized by recurrent skin swelling, abdominal pain, and potentially life-threatening upper airways obstruction. Knowledge of the molecular mechanisms leading from C1-INH deficiency to angioedema allowed the development of several therapies. The aim of this review article is to discuss the safety of currently available treatments of C1-INH-HAE. The authors give an insight on the mechanism of action and safety profile of drugs for treatment of acute attacks and for short- and long-term prophylaxis. Evidence from systematic reviews, clinical trials, retrospective studies, and case reports is summarized in this review. C1-INH-HAE is a disabling, life-threatening condition that lasts life-long. Different therapeutic approaches with different drugs provide significant benefit to patients. Safety profiles of these therapies are critical for optimal therapeutic decision and need to be known by C1-INH-HAE treating physicians for appropriate risk/benefit evaluation.


A Review of Chitosan and Chitosan Nanofiber: Preparation, Characterization, and Its Potential Applications.
Chitosan is produced by deacetylating the abundant natural chitin polymer. It has been employed in a variety of applications due to its unique solubility as well as its chemical and biological properties. In addition to being biodegradable and biocompatible, it also possesses a lot of reactive amino side groups that allow for chemical modification and the creation of a wide range of useful derivatives. The physical and chemical characteristics of chitosan, as well as how it is used in the food, environmental, and medical industries, have all been covered in a number of academic publications. Chitosan offers a wide range of possibilities in environmentally friendly textile processes because of its superior absorption and biological characteristics. Chitosan has the ability to give textile fibers and fabrics antibacterial, antiviral, anti-odor, and other biological functions. One of the most well-known and frequently used methods to create nanofibers is electrospinning. This technique is adaptable and effective for creating continuous nanofibers. In the field of biomaterials, new materials include nanofibers made of chitosan. Numerous medications, including antibiotics, chemotherapeutic agents, proteins, and analgesics for inflammatory pain, have been successfully loaded onto electro-spun nanofibers, according to recent investigations. Chitosan nanofibers have several exceptional qualities that make them ideal for use in important pharmaceutical applications, such as tissue engineering, drug delivery systems, wound dressing, and enzyme immobilization. The preparation of chitosan nanofibers, followed by a discussion of the biocompatibility and degradation of chitosan nanofibers, followed by a description of how to load the drug into the nanofibers, are the first issues highlighted by this review of chitosan nanofibers in drug delivery applications. The main uses of chitosan nanofibers in drug delivery systems will be discussed last.


Diversity of apolipoprotein E genetic polymorphism significance on cardiovascular risk is determined by the presence of metabolic syndrome among hypertensive patients.
Hypertension has a significant relevance as a cardiovascular risk factor. A consistent increase on world's Metabolic Syndrome (MetS) incidence has been associated with an epidemic cardiovascular risk in different populations. Dislipidemia plays a major role determining the epidemic CV burden attributed to MetS. Apolipoprotein E (ApoE) is involved on cholesterol and triglycerides metabolism regulation. Once ApoE polymorphism may influence lipid metabolism, it is possible that it brings on individual susceptibility consequences for the development of MetS and cardiovascular risk. The objective of the study is to measure the discriminatory power of ApoE polymorphism in determining cardiovascular risk stratification based on the presence MetS in a cohort of hypertensive patients. It was enrolled 383 patients, divided in two groups, classified by MetS presence (IDF criteria): Group 1: 266 patients with MetS (MetS +) and Group 2: 117 patients without Mets (MetS -). Patient's data were collected by clinical evaluation, physical exam, file reviews and laboratory testing. Polymorphic ApoE analysis was performed by PCR amplification. Groups were compared on clinical and laboratory characteristics as well as allele and genotype distribution towards ApoE polymorphism. Mets CVD prevalence was analysed according to E4 allele prevalence. The results evidenced 184 men (48%), 63,7% whites, 45,1% diabetics and 11,7% of patients were smokers. Mean age was 64,0 ± 12,0 years. When genotypic distribution was analyzed, E3/3 genotype and E3 allele frequencies were more prevalent. Among patients with MetS, we observed an independent association between CVD prevalence and E4 allele frequency (OR 2.42 (1.17- 5.0, p < 0,05)). On the opposite direction, in those without MetS, there was lesser CVD burden in E4 allele carriers (OR 0,14 (0,02-0,75)). These associations remained significant even after confounding factor corrections. The results presented demonstrate that the association between ApoE gene and CVD may be modulated by the presence of MetS, with an increased CV burden observed among E4 allele carriers with the syndrome. On the opposite way, E4 allele carriers without visceral obesity had lesser prevalence of CVD.


18F-FDG-PET/CT-guided intensity-modulated radiotherapy for 42 FIGO III/IV ovarian cancer: A retrospective study.
The aim of the present study was to evaluate the curative effect of fludeoxyglucose-positron emission tomography/computed tomography (18F-FDG-PET/CT)-guided intensity-modulated radiotherapy (IMRT) for 42 patients with International Federation of Gynecology and Obstetrics (FIGO) stage III/IV ovarian cancer. Between January 2012 and December 2015, 42 patients with FIGO stage III/IV ovarian cancer who were treated with 18F-FDG-PET/CT-guided IMRT at the Department of Radiation Oncology were analyzed. A total of 21 patients who exhibited recurrence following surgery and 11 patients who were unable to tolerate or rejected surgery received 5-10 cycles of chemotherapy only. A total of 10 patients, who were either older (>70 years) or in poor general health were unable to undergo surgery and only received IMRT. The patients received a total radiation dose of 5,040 cGy (range, 4,500-5,500 cGy), with a dose fraction of 200 cGy/fx, administered a total of 10-14 times, 5 times/week, prior to being rested for half an hour to relocate lesions and undergoing a second round of radiotherapy for 10-14 cycles. The 1-, 2- and 3-year progression-free survival (PFS) rates of the patients were 66.7, 33.3 and 21.4%, respectively, and the median PFS time was 20.3 months. The 1-, 2- and 3-year local control rates of the patients were 90.5, 83.3 and 69.0%, respectively, and the 1-, 2- and 3-year overall survival (OS) rates were 73.8, 64.3 and 52.4%, respectively. According to the results of multivariate analysis using the Cox proportional hazards model, the Karnofsky performance status (KPS) score (1) was the only index associated with prognosis (P<0.003). The study concluded that for patients with advanced ovarian cancer, particularly for patients unable to undergo surgery or chemotherapy, 18F-FDG PET/CT-guided IMRT is a safe and effective treatment method, and it may be considered as an equally effective treatment option. Furthermore, the results of the present study suggested that the KPS score of a patient is the only factor affecting the OS time.


First-Principles Assessment of CdTe as a Tunnel Barrier at the α-Sn/InSb Interface.
Majorana zero modes, with prospective applications in topological quantum computing, are expected to arise in superconductor/semiconductor interfaces, such as β-Sn and InSb. However, proximity to the superconductor may also adversely affect the semiconductor's local properties. A tunnel barrier inserted at the interface could resolve this issue. We assess the wide band gap semiconductor, CdTe, as a candidate material to mediate the coupling at the lattice-matched interface between α-Sn and InSb. To this end, we use density functional theory (DFT) with Hubbard U corrections, whose values are machine-learned via Bayesian optimization (BO) [ npj Computational Materials 2020, 6, 180]. The results of DFT+U(BO) are validated against angle resolved photoemission spectroscopy (ARPES) experiments for α-Sn and CdTe. For CdTe, the z-unfolding method [ Advanced Quantum Technologies 2022, 5, 2100033] is used to resolve the contributions of different kz values to the ARPES. We then study the band offsets and the penetration depth of metal-induced gap states (MIGS) in bilayer interfaces of InSb/α-Sn, InSb/CdTe, and CdTe/α-Sn, as well as in trilayer interfaces of InSb/CdTe/α-Sn with increasing thickness of CdTe. We find that 16 atomic layers (3.5 nm) of CdTe can serve as a tunnel barrier, effectively shielding the InSb from MIGS from the α-Sn. This may guide the choice of dimensions of the CdTe barrier to mediate the coupling in semiconductor-superconductor devices in future Majorana zero modes experiments.


Carbonyl groups as molecular valves to regulate chloride binding to squaramides.
Environment-sensitive binding of anions to synthetic receptors is important for the functional mimicry of ion channels. We describe new squaramide-based chloride ion receptors whose anion binding cavity can be opened and closed by using carbonyl groups as valves. In nonpolar solvents, the carbonyls preclude chloride binding via intramolecular hydrogen bonding with the squaramide NHs. In polar solvents, disruption of the intramolecular hydrogen bonds reorients the carbonyl groups and opens the anion-binding cavity.


[The amniotic infection syndrome and premature rupture of the amnion. Manifest and threatening unspecific intra-uterine infections of the last third of pregnancy (author's transl)].
In the last third of pregnancy the unspecific bacterial diseases of placenta, umbilical cord and membranes differ from those in earlier months [154; 155; 85]. There is a parallel change in the localization of fetal organs affected. Pathologic anatomical clarification of this led to the conceptual definition of the rare extra-amnial placental-fetal path of infection on the one hand and of primary intra-amnial infection with secondary chorion-amnionitis on the other hand and to identification of the amniotic infection syndrome as a typical entity at the end of pregnancy [19]. While the amnionic sac is closed, unspecific fetal inflammation is rare. Generally this happens only after rupture of the membranes. Since the amniotic infection syndrome often produces only minor clinical symptoms and since fetal infection probably starts early, one searched for means of assessing the risk of infection independently from symptoms. In comparative series of investigations of pregnancies with and without premature rupture of the membranes, cases of neonatal death from infection were preceded by signs of inflammation in placenta, umbilical cord and membranes. Together with the fetal and maternal infections they depended on the length of time between rupture and the onset of labor. pns. The data now available give a clear picture of the development of the inflammatory processes in mature and premature children and suffice for the assessment of fetal and maternal risks.


Polygamy, economic security and well-being of retired Zulu migrant workers.
Why does polygamy still persist when changing circumstances challenge the conventional wisdom that polygamy and numerous progeny provide social security in old age? To answer this question an in-depth questionnaire survey of 253 retired Zulu male migrants resident in rural areas examined the relationship between polygamy, economic security, and quality of life after return migration. Results indicate that polygamous marital status contributes only indirectly to feelings of enhanced well-being relative to economic advantage and good health. It is concluded that despite changing economic circumstances a traditionally-oriented polygamous head of a Zulu household may still expect to feel optimistic about his social and spiritual security in old age. Further research is required to explore Zulu women's views regarding the longer-term advantages of polygamy throughout the life course.


Epitope mapping of the HIV-1 gag region by analysis of gag gene deletion fragments expressed in Escherichia coli defines eight antigenic determinants.
Immune response to HIV infection is generally characterized by appearance of antibodies to the gag protein p24 early in infection, and by apparent loss of p24 antibodies accompanied by increases in p24 antigen levels with disease progression. Precise definition of the immunodominant epitopes present in gag gene proteins has potential clinical significance. Seventeen anti-gag monoclonal antibodies (MAb) were used in enzyme-linked immunosorbent assays (ELISA) with antigens expressed by nine recombinant clones to define epitopes on HIV gag proteins which elicit an immune response. All of the MAbs tested, except two anti-p17, reacted with a clone which expresses the carboxyl terminal 13 amino acids of p17 and all of p24 and p15. All anti-p24 MAbs reacted with clones containing all of p24. MAbs reacted differentially with clones containing deleted regions depending on the antigenic portion expressed. Of thirteen potential identifiably different genomic regions which could be predicted from the genomic structure of the clones, eight different antigen epitopes were defined: two on p17, five on p24, and one on p15 (in the region corresponding to the carboxyl terminal protein p6). Six regions did not appear to react with any of the monoclonal antibodies available. Identification of the epitopes present in the cloned antigens should allow their use to evaluate sera from HIV-infected donors at different clinical stages of progression to AIDS.


Day-Night Patterns of Epileptiform Activity in 65 Patients With Long-Term Ambulatory Electrocorticography.
To characterize cyclic day-night patterns of electrocorticographic epileptiform activity (EA) in patients with focal onset seizures. Epileptiform events as defined by the physician (also termed more generally as "epileptiform activity" or EA) were recorded in 65 patients with partial onset (also referred to as "focal onset") seizures using the RNS System, which includes a cranially implanted neurostimulator connected to 1 or two 4-contact leads placed at the seizure focus. The neurostimulator is programmed to detect specific patterns of electrocorticographic activity and to provide responsive stimulation. The 24-hour periodicity of detections of EA was analyzed for individual patients and for subgroups of patients according to the type of EA, laterality, lobe of onset, and whether the onset was neocortical or hippocampal. The time of day when peaks in EA occurred was also analyzed. There were robust circadian patterns of detections of EA in most patients, with a primary peak in detections at night and a secondary peak in the late afternoon in some cases. Subset analyses were performed by lobe, region of the brain, and type of cortex (neocortical vs. hippocampal); significant circadian rhythmicity was present in all subsets. This is the first report of circadian cycles of EA as assessed through chronic ambulatory electrocorticographic recordings in adults with focal onset seizures. Epileptiform activity displayed circadian patterns in the majority of these patients. These findings suggest that epilepsy therapies might be optimized by adjusting the timing of therapy according to each patient's unique circadian pattern of EA.


Association between global DNA methylation (LINE-1) and occupational particulate matter exposure among informal electronic-waste recyclers in Ghana.
This study examined the associations between PM (2.5 and 10) and global DNA methylation among 100 e-waste workers and 51 non-e-waste workers serving as controls. Long interspersed nucleotide repetitive elements-1 (LINE-1) was measured by pyrosequencing. Personal PM2.5 and PM10 were measured over a 4-hour work-shift using real-time particulate monitors incorporated into a backpack . Linear regression models were used to assess the association between PM and LINE-1 DNA methylation. The concentrations of PM2.5 and PM10 were significantly higher among the e-waste workers than the controls (77.32 vs 34.88, p < 0.001 and 210.21 vs 121.92, p < 0.001, respectively). PM2.5 exposure was associated with increased LINE-1 CpG2 DNA methylation (β = 0.003; 95% CI; 0.001, 0.006; p = 0.022) but not with the average of all 4 CpG sites of LINE-1. In summary, high levels of PM2.5 exposure was associated with increased levels of global DNA methylation in a site-specific manner.


Accuracy of an administrative database for pancreatic cancer by international classification of disease 10th codes: A retrospective large-cohort study.
Korean National Health Insurance (NHI) claims database provides large-cohort. However, studies regarding accuracy of administrative database for pancreatic cancer (PC) have not been reported. We aimed to identify accuracy of NHI database regarding PC classified by international classification of disease (ICD)-10 codes. To identify the accuracy and usefulness of administrative database in PC and the accurate ICD codes for PC with location. Study and control groups were collected from 2003 to 2016 at Seoul National University Bundang Hospital. Cases of PC were identified in NHI database by international classification of diseases, 10th revision edition (ICD-10 codes) supported with V codes. V code is issued by medical doctors for covering 95% of medical cost by Korean government. According to pathologic reports, definite or possible diagnoses were defined using medical records, images, and pathology. A total of 1846 cases with PC and controls were collected. Among PC, only 410 (22.2%) cases were identified as specific cancer sites including head in 234 (12.7%) cases, tail in 104 (5.6%) cases and body in 72 (3.9%) cases. Among PC, 910 (49.3%) cases were diagnosed by definite criteria. Most of these were adenocarcinoma (98.0%). The rates of definite diagnosis of PC were highest in head (70.1%) followed by body (47.2%) and tail (43.3%). False-positive cases were pancreatic cystic neoplasm and metastasis to the pancreas. In terms of the overall diagnosis of PC, sensitivity, specificity, positive predictive value, and negative predictive value were 99.95%, 98.72%, 98.70%, and 99.95%, respectively. Diagnostic accuracy was similar both in terms of diagnostic criteria and tumor locations. Korean NHI claims database collected according to ICD-10 code with V code for PC showed good accuracy.


Novel approaches toward preferential detection of viable cells using nucleic acid amplification techniques.
This article elaborates on possible future directions for microbial viability assessment using nucleic acid-modifying compounds in combination with DNA- (and potentially RNA-) amplification technologies. Bacteria were traditionally considered viable when they could be cultured, whereas today's viability concept is based on the presence of some form of metabolic activity, responsiveness, RNA transcripts that tend to degrade rapidly after cell death, or of an intact membrane. The latter criterion was the focus of recent approaches to limit detection to intact cells using ethidium monoazide or propidium monoazide. Membrane integrity must, however, be considered as a very conservative criterion for microbial viability. The new concept presented here aims at limiting nucleic acid-based detection to cells with an active metabolism, which might be a more appropriate viability criterion. To selectively detect only cells with metabolic and respiratory activity (while excluding inactive dead cells from detection), we suggest the use of 'activity-labile compounds'. In addition to their potential usefulness for viability assessment, these new compounds could also be beneficial for selectively amplifying nucleic acids of cells that have metabolic activities of interest. This preferential detection of microorganisms with certain metabolic capabilities is referred to as 'molecular enrichment' in distinction to 'growth enrichment'.


Nutritional status of primary school children with endemic goitre in Caprivi, Namibia.
The nutritional status of primary school children living in an endemic goitre area in eastern Caprivi, Namibia, was assessed by means of clinical, biochemical, anthropometrical and dietetic observations. An approximately 20 pc sample, consisting of 380 primary school children, aged six to 18 years and representing eight schools in the Cuando River area of eastern Caprivi, was included in the study. Their goitre prevalence of 34.5 pc has been reported earlier. A significantly lower mean thyroxine level in goitrous compared to non-goitrous children indicated that dietary iodine deficiency was the primary cause of the endemic goitre. The present paper focuses on the nutritional status of these primary school children. Anthropometrically, these children were severely undernourished, as indicated by a high prevalence of low (below the third NCHS percentile) weight and height for age values, ranging from 38.0 pc to 55.9 pc. Dietary analysis revealed a low energy intake as well as dietary deficiencies in folic acid (only girls), ascorbic acid, vitamin A, nicotinic acid, iron, riboflavin and calcium. A high percentage (43.9 pc of boys and 33.7 pc of girls) of the children were biochemically anaemic whilst less than one pc of the children showed clinical signs of anaemia. Nutritional intervention programmes in this area should not only treat and prevent the endemic goitre but also attend to the energy and micro-nutrient deficiencies in these children.


Predicting pressure-dependent unimolecular rate constants using variational transition state theory with multidimensional tunneling combined with system-specific quantum RRK theory: a definitive test for fluoroform dissociation.
Understanding the falloff in rate constants of gas-phase unimolecular reaction rate constants as the pressure is lowered is a fundamental problem in chemical kinetics, with practical importance for combustion, atmospheric chemistry, and essentially all gas-phase reaction mechanisms. In the present work, we use our recently developed system-specific quantum RRK theory, calibrated by canonical variational transition state theory with small-curvature tunneling, combined with the Lindemann-Hinshelwood mechanism, to model the dissociation reaction of fluoroform (CHF3), which provides a definitive test for falloff modeling. Our predicted pressure-dependent thermal rate constants are in excellent agreement with experimental values over a wide range of pressures and temperatures. The present validation of our methodology, which is able to include variational transition state effects, multidimensional tunneling based on the directly calculated potential energy surface along the tunneling path, and torsional and other vibrational anharmonicity, together with state-of-the-art reaction-path-based direct dynamics calculations, is important because the method is less empirical than models routinely used for generating full mechanisms, while also being simpler in key respects than full master equation treatments and the full reduced falloff curve and modified strong collision methods of Troe.


Age-related changes in trabecular bone microdamage initiation.
With age, alterations occurring in bone quality, quantity, and microarchitecture affect the resistance of trabecular bone to local failure. The clinical implications of these changes are evident by the observed exponential increase in fracture incidence with age. Although age-related development of skeletal fragility is well established, it is unclear how the local failure properties of bone change with age. We previously reported a specimen-specific technique to assess microstructural stresses and strains associated with microdamage initiation but did not assess age-related changes. In this study, we compared younger (average age 2 years) and older (average age 10 years) bovine trabecular bone to evaluate how alterations in bovine bone quantity and quality with age affect the local mechanical environment associated with microdamage formation. The results show strong positive correlations between microdamage and local stresses and strains for both younger and older bovine trabecular bone. Correlation strength was slightly improved (<8%) for some parameters by incorporating heterogeneous local material properties based on mineral density into the finite element models. Within individual trabeculae, average stresses and strains were significantly higher in microdamaged trabeculae compared to randomly selected undamaged trabeculae, regardless of age. However, damaged trabeculae in older bone were found to have higher stresses and lower strains than those from younger bone. Corresponding differences in mineral density, microarchitecture, and FEM-determined local material properties were also observed between the two groups. Taken together, these data suggest marked age-related changes in the mechanics of microdamage initiation at the trabecular level. The combined experimental, computational, and histochemical approaches used in this study provide an improved understanding of microdamage initiation and bone quality.


Nerve Injuries after Glenohumeral Dislocation, a Systematic Review of Incidence and Risk Factors.
Glenohumeral dislocation is a common shoulder injury that can result in nerve injury. However, the full impact of these injuries on patient function and recovery remains unclear. This systematic review aimed to determine (1) the incidence, (2) risk factors, and (3) functional outcomes following nerve injuries after glenohumeral dislocation. The study followed PRISMA guidelines and used the PICO strategy. PubMed, EMBASE, Scopus, and Cochrane Collaboration Library databases were searched for studies. Two reviewers independently assessed the study eligibility, and data extraction was conducted by two authors. The quality of included studies was assessed using the Methodological Index for Non-Randomized Studies (MINORS) criteria. Thirteen studies comprising 17,087 patients were included. The incidence of nerve injury ranged from 0.4% to 65.5%, with the axillary nerve being most commonly affected. The time to reduction did not significantly affect the incidence of nerve injury. The mechanism of injury, the affected side, associated injuries, and recovery time were found to be potential risk factors for nerve injury. Motor recovery was incomplete in many patients, and sensory recovery was less complete. By synthesizing the available evidence, this systematic review underscores the importance of considering nerve injury in the management of patients with glenohumeral dislocations. Future research can build on these findings to develop targeted prevention and treatment approaches that optimize patient outcomes.


Validity and reliability of the CatWalk system as a static and dynamic gait analysis tool for the assessment of functional nerve recovery in small animal models.
A range of behavioral testing paradigms have been developed for the research of central and peripheral nerve injuries with the help of small animal models. Following any nerve repair strategy, improved functional outcome may be the most important evidence of axon regeneration. A novel automated gait analysis system, the CatWalk™, can measure dynamic as well as static gait patterns of small animals. Of most interest in detecting functional recovery are in particular dynamic gait parameters, coordination measures, and the intensity of the animals paw prints. This article is designed to lead to a more efficient choice of CatWalk parameters in future studies concerning the functional evaluation of nerve regeneration and simultaneously add to better interstudy comparability. The aims of the present paper are threefold: (1) to describe the functional method of CatWalk gait analysis, (2) to characterize different parameters acquired by CatWalk gait analysis, and to find the most frequently used parameters as well as (3) to compare their reliability and validity throughout the different studies. In the reviewed articles, the most frequently used parameters were Swing Duration (30), Print Size (27), Stride Length (26), and Max Contact Area (24). Swing Duration was not only frequently used but was also the most reliable and valid parameter. Therefore, we hypothesize that Swing Duration constitutes an important parameter to be chosen for future studies, as it has the highest level of reliability and validity. In conclusion, CatWalk can be used as a complementary approach to other behavioral testing paradigms to assess clinically relevant behavioral benefits, with the main advantage that this system demonstrates both static and dynamic gait parameters at the same time. Due to limited reliability and validity of certain parameters, we recommend that only the most frequently assessed parameters should be used in the future.


Antiangiogenic Effects of Nerve Growth Factor Loop 4 Monomeric Dipeptide Mimetic.
The effects of GK-1, a monomeric dipeptide mimetic of nerve growth factor (NGF) loop 4, on angiogenesis were studied in vitro and in vivo. Experiments on human umbilical vein endothelial cells HUVEC showed that the test compound did not affect tubulogenesis (initial stage of angiogenesis) and prevented realization of the angiogenic effect of NGF and its dimeric dipeptide mimetic GK-2. Experiments on rat hind limb ischemia model demonstrated that GK-1 (1 mg/kg/day intraperitoneally over 14 days) significantly reduced the density of the capillary network in ischemic tissue and increased the number and area of Zenker necrosis in comparison with the control. These data suggest that GK-1 exhibits a pronounced antiangiogenic activity.


Carotenoid-Chlorophyll Interactions in a Photosynthetic Antenna Protein: A Supramolecular QM/MM Approach.
Multichromophoric interactions control the initial events of energy capture and transfer in the light harvesting peridinin-chlorophyll a protein (PCP) from marine algae dinoflagellates. Due to the van der Waals association of the carotenoid peridinin (Per) with chlorophyll a in a unique 4:1 stoichiometric ratio, supramolecular quantum mechanical/molecular mechanical (QM/MM) calculations are essential to accurately describe structure, spectroscopy, and electronic coupling. We show that, by enabling inter-chromophore electronic coupling, substantial effects arise in the nature of the transition dipole moment and the absorption spectrum. We further hypothesize that inter-protein domain Per-Per interactions are not negligible, and are needed to explain the experimental reconstruction features of the spectrum in wild-type PCP.


Implicit Stochastic Gradient Descent Method for Cross-Domain Recommendation System.
The previous recommendation system applied the matrix factorization collaborative filtering (MFCF) technique to only single domains. Due to data sparsity, this approach has a limitation in overcoming the cold-start problem. Thus, in this study, we focus on discovering latent features from domains to understand the relationships between domains (called domain coherence). This approach uses potential knowledge of the source domain to improve the quality of the target domain recommendation. In this paper, we consider applying MFCF to multiple domains. Mainly, by adopting the implicit stochastic gradient descent algorithm to optimize the objective function for prediction, multiple matrices from different domains are consolidated inside the cross-domain recommendation system (CDRS). Additionally, we design a conceptual framework for CDRS, which applies to different industrial scenarios for recommenders across domains. Moreover, an experiment is devised to validate the proposed method. By using a real-world dataset gathered from Amazon Food and MovieLens, experimental results show that the proposed method improves 15.2% and 19.7% in terms of computation time and MSE over other methods on a utility matrix. Notably, a much lower convergence value of the loss function has been obtained from the experiment. Furthermore, a critical analysis of the obtained results shows that there is a dynamic balance between prediction accuracy and computational complexity.


Effects of physiological hyperinsulinemia on counterregulatory response to prolonged hypoglycemia in normal humans.
To test the hypothesis that differing physiological insulin levels can modify the counter-regulatory response to prolonged hypoglycemia, experiments were carried out in 10 healthy male subjects. Insulin was infused subcutaneously for 8 h in two separate randomized protocols, so that steady-state levels of 132 +/- 6 pM (low) and 402 +/- 18 pM (high) were obtained. The fall in plasma glucose was controlled by the glucose-clamp technique. Plasma glucose fell slowly and similarly in both groups, reaching an identical steady-state (final 120 min of each study) level of 3.4 +/- 0.1 mM. Steady-state plasma epinephrine (2.5 +/- 0.4 vs. 1.5 +/- 0.2 nM) and norepinephrine (1.5 +/- 0.2 vs. 1.1 +/- 0.1 nM) were significantly (P < 0.05) greater during high- compared with low-dose insulin infusions. Plasma glucagon was reduced during high compared with low infusions (104 +/- 9 vs. 150 +/- 19 ng/l, P < 0.05). Growth hormone, cortisol, and pancreatic polypeptide increased significantly but were not different during the two insulin infusions. Hepatic glucose production (HGP) was equal during the steady-state period (8.4 +/- 1.0 mumol.kg-1.min-1) of each infusion. Blood lactate levels (1,255 +/- 73 vs. 788 +/- 69 mumol/l, P < 0.02) were increased in high compared with low, but nonesterified fatty acid (205 +/- 43 vs. 579 +/- 65 mumol/l) and 3-hydroxybutyrate (40 +/- 36 vs. 159 +/- 51 mumol/l) were reduced (P < 0.002) during the high-compared with low-dose infusions.(ABSTRACT TRUNCATED AT 250 WORDS)


Immunoglobulin A deposition in jejunal mucosa of children with dermatitis herpetiformis.
Previously we have shown by indirect immunofluorescence (IF) technique that a special IgA antibody in the sera of patients with dermatitis herpetiformis (DH) binds to the structures of the normal jejunum. Now we show by direct IF that specific IgA deposits are present in the proximal jejunum of 11/12 DH and 2/2 celiac patients before a gluten-free diet (GFD). The IgA deposition was in a tubular pattern underlying the villous and crypt epithelial basement membranes and in the lamina propria. This IgA deposition diminished or was not detectable in DH patients under a GFD for a year, and became detectable under gluten challenge in three DH patients. One patient with celiac disease and IgA deficiency, four with other intestinal diseases, and four without jejunal damage had neither jejunal IgA deposition nor circulating IgA anti-jejunal antibody. The deposition of IgA in the jejunum seemed to be correlated with the presence of IgA anti-jejunal antibody in the serum and with the presence of jejunal damage, but the degree of jejunal atrophy, the titer of the anti-jejunal antibody, and the intensity of jejunal IgA deposition in DH patient were not clearly related. Deposition of IgA in the jejunum in DH did not clearly correlate with the activity of the skin symptoms and thus may not be directly related to the pathogenesis of the skin disease of DH.


Baroreceptor unloading does not limit forearm sweat rate during severe passive heat stress.
This study tested the hypothesis that sweat rate during passive heat stress is limited by baroreceptor unloading associated with heat stress. Two protocols were performed in which healthy subjects underwent passive heat stress that elicited an increase in intestinal temperature of ∼1.8°C. Upon attaining this level of hyperthermia, in protocol 1 (n = 10, 3 females) a bolus (19 ml/kg) of warm (∼38°C) isotonic saline was rapidly (5-10 min) infused intravenously to elevate central venous pressure (CVP), while in protocol 2 (n = 11, 5 females) phenylephrine was infused intravenously (60-120 μg/min) to return mean arterial pressure (MAP) to normothermic levels. In protocol 1, heat stress reduced CVP from 3.9 ± 1.9 mmHg (normothermia) to -0.6 ± 1.4 mmHg (P < 0.001), while saline infusion returned CVP to normothermic levels (5.1 ± 1.7 mmHg; P > 0.999). Sweat rate was elevated by heat stress (1.21 ± 0.44 mg·cm(-2)·min(-1)) but remained unchanged during rapid saline infusion (1.26 ± 0.47 mg·cm(-2)·min(-1), P = 0.5), whereas cutaneous vascular conductance increased from 77 ± 10 to 101 ± 20% of local heating max (P = 0.029). In protocol 2, MAP was reduced with heat stress from 85 ± 7 mmHg to 76 ± 8 mmHg (P = 0.048). Although phenylephrine infusion returned MAP to normothermic levels (88 ± 7 mmHg; P > 0.999), sweat rate remained unchanged during phenylephrine infusion (1.39 ± 0.22 vs. 1.41 ± 0.24 mg·cm(-2)·min(-1); P > 0.999). These data indicate that both cardiopulmonary and arterial baroreceptor unloading do not limit increases in sweat rate during passive heat stress.


Transesophageal echocardiography through nasal way as a guide to percutaneous closure of patent foramen ovale.
Percutaneous device closure of patent foramen ovale (PFO) has become an effective and safe alternative to medical or surgery treatment. Transesophageal echocardiography (TEE), as commonly used to guide this procedure, has the limitation to require general anesthesia. Recently, intracardiac echocardiography (ICE) with AcuNav probe was used to guide percutaneous PFO closure. We report a 42 year-old man with two previous cryptogenetic strokes in whom both diagnosis and guidance of PFO closure were performed by means of TEE using the AcuNav catheter introduced through nasal way (TEENW). This technique, that does not require general anesthesia, provided adequate and complete view of the Amplatzer procedure. TEENW might offer a feasible and equivalent echocardiographic alternative either to standard TEE or ICE as a guide to percutaneous PFO closure.


Thermal stability of calmodulin and mutants studied by (1)H-(15)N HSQC NMR measurements of selectively labeled [(15)N]Ile proteins.
Calmodulin, the Ca(2+)-dependent activator of many cellular processes, contains two well-defined structural domains, each of which binds two Ca(2+) ions. In its Ca(2+)-free (apo) form, it provides an attractive model for studying mechanisms of protein unfolding, exhibiting two separable, reversible processes, indicating two structurally autonomous folding units. (1)H-(15)N HSQC NMR in principle offers a detailed picture of the behavior of individual residues during protein unfolding transitions, but is limited by the lack of dispersion of resonances in the unfolded state. In this work, we have used selective [(15)N]Ile labeling of four distinctive positions in each calmodulin domain to monitor the relative thermal stability of the folding units in wild-type apocalmodulin and in mutants in which either the N- or C-domain is destabilized. These mutations lead to a characteristic perturbation of the stability (T(m)) of the nonmutated domain relative to that of wild-type apocalmodulin. The ability to monitor specific (15)N-labeled residues, well-distributed throughout the domain, provides strong evidence for the autonomy of a given folding unit, as well as providing accurate measurements of the unfolding parameters T(m) and DeltaH(m). The thermodynamic parameters are interpreted in terms of interactions between one folded and one unfolded domain of apocalmodulin, where stabilization on the order of a few kilocalories per mole is sufficient to cause significant changes in the observed unfolding behavior of a given folding unit. The selective (15)N labeling approach is thus a general method that can provide detailed information about structural intermediates populated in complex protein unfolding processes.


Glyceryl Tribenzoate: A Flavoring Ingredient, Inhibits the Adoptive Transfer of Experimental Allergic Encephalomyelitis via TGF-β: Implications for Multiple Sclerosis Therapy.
Multiple sclerosis (MS) is the most common autoimmune demyelinating disease of the central nervous system (CNS). Here, we have explored a novel use of glyceryl tribenzoate (GTB), a flavoring ingredient, in ameliorating the disease process of experimental allergic encephalomyelitis (EAE), an animal model of MS, via TGF-β. Oral feeding of GTB suppressed clinical symptoms of adoptively-transferred relapsing-remitting (RR) EAE in recipient mice and suppressed the generation of encephalitogenic T cells in donor mice. GTB also attenuated clinical symptoms of RR-EAE in PLP-TCR transgenic mice and chronic EAE in male C57/BL6 mice. Accordingly, GTB also suppressed perivascular cuffing, preserved the integrity of blood-brain barrier and blood-spinal cord barrier, inhibited inflammation, and stopped demyelination in the CNS of EAE mice. Interestingly, GTB treatment upregulated TGF-β and enriched regulatory T cells (Tregs) in splenocytes as well as in vivo in EAE mice. Blocking TGF-β by neutralizing antibodies abrogated GTB-mediated enrichment of Tregs and protection of EAE. These results suggest that oral GTB may be considered as a possible therapy for MS patients.


Impact of -2 degrees C superchilling before refrigerated storage (4 and 8 degrees C) on the microbiological and sensory qualities of cold-smoked salmon.
Detection and enumeration of Listeria monocytogenes and total spoilage bacteria in 40 batches of cold-smoked salmon (one batch = 42 products from the same day of manufacture) straight from the factory were carried out. If L. monocytogenes was detected in at least one of the nine samples analyzed on receipt at the laboratory, 9 products of the same batch were stored for 10 days at 4 degrees C, which was followed by 18 days at 8 degrees C (control), 12 products were superchilled for 14 days at -2 degrees C, and 12 other products were superchilled for 28 days at -2 degrees C and then stored under the same conditions as the control was stored. L. monocytogenes was detected in 7% of the 40 batches analyzed immediately after receipt at the laboratory. L. monocytogenes prevalence was similar (approximately 25%) throughout the storage at 4 and 8 degrees C, both in control and super-chilled products at -2 degrees C for 14 days. After superchilling for 28 days at -2 degrees C, L. monocytogenes was found in 9% of products, and in 39% at the end of the storage above 0 degree C. Moreover, the L. monocytogenes count was higher after 3 and 4 weeks of storage at 4 and 8 degrees C in products superchilled 28 days at -2 degrees C than in control products or in products superchilled for 14 days. Serotype 1/2a-3a and nine genetic groups were identified and found throughout the storage scenario. At the end of shelf life, sensory characteristics of products superchilled for 28 days at -2 degrees C were slightly modified. A decrease in firmness associated with increased tearing of salmon slices was observed as well as a slight amine odor.


Microperimetry in multiple evanescent white dot syndrome.
This study investigates a new instrument, called the Microperimeter-1 (MP-1), which maps areas of retinal sensitivity, in a series of patients with multiple evanescent white dot syndrome (MEWDS). A retrospective observational case series from a private retina practice, in which 3 patients with a diagnosis of MEWDS underwent testing with the MP-1. All 3 patients in this series showed an enlarged blind spot on MP-1 testing. Microperimetry is a useful tool in visual field testing for patients with MEWDS. The MP-1 allows retinal sensitivity mapping to be displayed on a fundus photograph, which permits correlation of scotomata with retinal pathology.


Microtubule-associated protein SlMAP70 interacts with IQ67-domain protein SlIQD21a to regulate fruit shape in tomato.
Tomato (Solanum lycopersicum) fruit shape is related to microtubule organization and the activity of microtubule-associated proteins (MAPs). However, insights into the mechanism of fruit shape formation from a cell biology perspective remain limited. Analysis of the tissue expression profiles of different microtubule regulators revealed that functionally distinct classes of MAPs, including members of the plant-specific MICROTUBULE-ASSOCIATED PROTEIN 70 (MAP70) and IQ67 DOMAIN (IQD, also named SUN in tomato) families, are differentially expressed during fruit development. SlMAP70-1-3 and SlIQD21a are highly expressed during fruit initiation, which relates to the dramatic microtubule pattern rearrangements throughout this developmental stage of tomato fruits. Transgenic tomato lines overexpressing SlMAP70-1 or SlIQD21a produced elongated fruits with reduced cell circularity and microtubule anisotropy, while their loss-of-function mutants showed the opposite phenotype, harboring flatter fruits. Fruits were further elongated in plants coexpressing both SlMAP70-1 and SlIQD21a. We demonstrated that SlMAP70s and SlIQD21a physically interact and that the elongated fruit phenotype is likely due to microtubule stabilization induced by the SlMAP70-SlIQD21a interaction. Together, our results identify SlMAP70 proteins and SlIQD21a as important regulators of fruit elongation and demonstrate that manipulating microtubule function during early fruit development provides an effective approach to alter fruit shape.


Identification of histidine 25 as the heme ligand in human liver heme oxygenase.
Electronic and resonance Raman spectroscopic studies are reported for the His25Ala mutant of human liver heme oxygenase (HO) and its complex with heme. In the oxidized (ferric) form of the enzyme.substrate complex, the heme is shown to be in a high-spin, five-coordinate state. This is distinct from the same complex in the wild-type enzyme in which the heme is six-coordinate, ligated to a proximal histidine and a water molecule in an environment reminiscent of aquometmyoglobin. The reduced (ferrous) form of the complex of the H25A heme oxygenase mutant has lost the very prominent resonance Raman band at approximately 217 cm-1 seen in the wild-type complex that has been unambiguously assigned to the proximal Fe-N(His) vibrational frequency [Sun et al. (1993) Biochemistry 32, 14151; Takahashi et al. (1994) Biochemistry 33, 1010]. The absence of this band in the spectrum of the mutant protein definitively identifies His 25 as the proximal ligand of the heme substrate. Furthermore, this ferrous heme-H25A HO complex exists as an equilibrium mixture between a five-coordinate, high-spin species and a four-coordinate, intermediate-spin species. Although the H25A mutant protein shows no heme oxygenase activity, the heme is competent to bind carbon monoxide. Studies of the CO adduct of the H25A HO complex show v(CO) and v(Fe-CO) frequencies at 1960 and 529 cm-1, respectively, that are characteristic of a hydrophobic carbon monoxide binding site on a heme with a weak proximal ligand.(ABSTRACT TRUNCATED AT 250 WORDS)


Spontaneous iron overload in alpha-thalassemic mice.
Because clinical disorders of spontaneous iron overload have no experimental counterpart, we studied iron distribution (atomic absorption analysis) and intestinal absorption (59Fe) in mice with hereditary alpha-thalassemia. Mice heterozygous for a radiation-induced alpha-Hb gene deletion exhibit a mild hemolytic anemia, like the human condition, with microcytosis, reticulocytosis, splenomegaly, and chemical evidence of defective alpha-chain synthesis. Quantitative iron determination showed that total iron content in spleen, liver, and kidney, but not heart or lung, of adult alpha-thalassemic mice was greater (P less than .05) than that in unaffected littermates. Iron concentration was also increased in liver (P less than .001), spleen (P = .025), kidney (P = .058), and heart (P = .010); in general, the greater the iron concentration in liver, the greater that in spleen (r = .39, P = .009), kidney (r = .70, P less than .001), and heart (r = .46, P less than .001). In mice examined 8 months postoperatively, splenectomy, as compared to sham operation, significantly raised iron content in extrasplenic tissues, but did not affect total body iron. At 10-11 weeks of age, but no longer at 12-14 weeks, thalassemic mice showed higher rates of iron absorption than age-matched controls. Thus, alpha-thalassemic mice display an early occurring iron absorption defect, leading to a modest, sustained, nonprogressive iron overload, and thereby represent a valuable model for exploring disorders of iron homeostasis.


Standardization and evaluation of botanical mixtures: lessons from a traditional Chinese herb, Epimedium, with oestrogenic properties.
Botanical extracts differ from conventional supplements in that they are complicated mixtures of many bioactive compounds. Here we describe our experience with a traditional Chinese medicinal plant Epimedium sp. to illustrate the scientific challenges of firstly, obtaining a standardized product from a complex mixture and secondly, evaluating that product for preclinical and clinical efficacy. In contrast, to its colloquial name 'Horny goat weed' and Internet advertisements as a herbal 'Viagra' for men, extracts of Epimedium are strongly oestrogenic due to the presence of novel potent phytoestrogens of the prenyl-flavone family. Since Epimedium is not cultivated, it was necessary to source for taxonomically identified samples and to authenticate their species by phylogenetic, chemical and bioresponse profiling. The feasibility of using a panel of oestrogen-responsive cell-based bioassays to measure summated oestrogenic effects at close time points for pharmacokinetic/pharmacodynamic (PK/PD) modelling was evaluated. We document proportionate oestrogenic responses in sera of animals fed oestrogenic drugs and botanical extracts, indicating that these target molecule responsive cell-based bioassays may have utility to capture the global effects of the myriad bioactive compounds in botanical extracts, informing the design of rigorous clinical trials for safety and efficacy.


FRAP beam-size analysis to measure palmitoylation-dependent membrane association dynamics and microdomain partitioning of Ras proteins.
Motions of membrane-associated proteins within and between membranes are essential for many cellular functions. We describe the application of fluorescence recovery after photobleaching (FRAP) beam-size analysis to investigate the role of palmitoylation in the membrane targeting and membrane association dynamics of H-Ras. The method described distinguishes between FRAP by lateral diffusion and by cytoplasmic exchange, and enables to obtain an estimate of the membrane affinity in live cells. These studies show distinct roles for the two palmitoylation sites (Cys181 and Cys184) on H-Ras, with different effects on membrane affinity and microlocalization.


Gut Microbiota and the Ways to Correct it in Chronic Kidney Disease.
Approximately 13% of the Russian population suffers from chronic kidney disease (CKD). Such a high prevalence of the disease, as well as the complexity and high cost of renal replacement therapy, explain the need for developing and implementing new approaches to treat patients at the pre-dialysis stages. The data collected in recent decades highlight the importance of gut microbiota in the progression of CKD. This review provides information about the microbiota composition in healthy individuals and patients with CKD and discusses the mechanisms of interaction in the intestine-kidney system. The article also presents the specifics of the violation of gut microbiota (GM) and correction thereof in CKD.


Rigorous expressions of Huygens' principle in scalar theory.
The Huygens' principle is thoroughly investigated under scalar theory. The rigorous expressions of Huygens' principle must be independent of ∂u/∂n, and their boundaries can only be taken as either spherical or flat; thus, three cases can be concluded. An extended version of Huygens' principle is proposed to cover these cases, whose rigorous expressions are shown in this paper. Specifically, when the radius of the spherical boundary approaches infinity, the corresponding expressions become the form corresponding to the flat boundary. Expressions with spherical boundary can change the area and average intensity of small angle diffraction pattern proportionally, thus providing a promising mathematical tool for the design of curved imaging systems.


[COMPLEX ASSESSMENT OF ENVIRONMENTAL FACTORS AND POSTVACCINAL IMMUNE STATE].
This article was written on the base of the analysis of data of protocols of annual serological sturdies of the post-vaccination immunity status in indicator groups of populations, the analysis of samples of drinking water air and soil with the assessment of the socio-economic development of mono-towns and rural settlements. In the article there is reflected the comprehensive assessment of environmental factors and specific features of the formation of socio-economic conditions of rural communities and mono towns. There was performed a comparative assessment of the status of post-vaccination immunity to infections controlled by specific means of prevention, in different age groups in mono towns and rural settlements. There was established a dependence of the formation of post-vaccination immunity on the state of environmental factors.


Molecular mechanisms of 3,3'4,4',5-pentachlorobiphenyl-induced epithelial-mesenchymal transition in human hepatocellular carcinoma cells.
Polychlorinated biphenyls (PCBs) are classic persistent organic pollutants (POPs). Many studies have found a positive association between the progression of hepatocellular carcinoma (HCC) and PCBs exposure. However, the influence of PCBs on epithelial-mesenchymal transition (EMT) of HCC remains to be unclear. In this study, we explored the effect of PCB126 on EMT in HCC cells and its underlying mechanisms. The data showed that PCB126, exposing both Bel-7402 and SMMC-7721 cells for 48h, promoted EMT that was demonstrated by E-cadherin repression, up-regulation of N-cadherin and vimentin, and morphological alteration. We found that signal transducer and activator of transcription 3 (STAT3)/Snail1 signaling was activated after PCB126 exposure, and the addition of STAT3 inhibitor WP1066 blocked PCB126-induced down-regulation of E-cadherin as well as up-regulation of N-cadherin and vimentin. Moreover, PCB126 exposure increased pyruvate kinase M2 (PKM2) expression and its nuclear translocation, whereas treatment with PKM2 shRNA suppressed the activation of STAT3/Snail1 signaling and the alternation of EMT-related molecules (E-cadherin, N-cadherin and vimentin). Furthermore, this study indicated estrogen receptor (ER) and aryl hydrocarbon receptor (AhR) were involved in PCB126-induced effects on PKM2, STAT3/Snail1 signaling and EMT by according treatment using ER inhibitor ICI and AhR shRNA. Notably, PCB126-increased reactive oxygen species (ROS) production via AhR is associated with activation of PKM2/STAT3/Snail1 cascades and contributes to EMT. Taken together, these results indicated that PCB126 promotes EMT process of HCC cells via PKM2/STAT3/Snail1 signaling which is mediated by ER and AhR.


Correlation of gingival stippling with periodontal phenotypical features: A cross-sectional study.
This study aimed at determining the correlation between gingival stippling (GS) and other phenotypical characteristics. Adult subjects in need of cone-beam computed tomography scans (CBCT) and comprehensive dental treatment in the maxillary anterior region were recruited. Facial gingival thickness [GT] and buccal bone thickness [BT] were assessed utilizing CBCT. Standardized intraoral photographs were obtained to determine keratinized tissue width (KTW), presence of GS in all facial and interproximal areas between the maxillary canines, and other variables of interest, such as gingival architecture (GA), tooth shape, and location. Statistical analyses to assess different correlations among recorded variables were conducted. A total of 100 participants and 600 maxillary anterior teeth constituted the study population and sample, respectively. Facial GS was observed in 56% of males and 44% of females, and it was more frequently associated with flat GA, triangular and square/tapered teeth, central incisors, and males. Greater mean values of GT, BT, and KTW were observed in facial areas that exhibited GS. Interdental GS was present in 73% of the sites and it was more frequently observed in males, the central incisor region, and when facial GS was present. Multilevel logistic regression revealed a statistically significant association between the presence of GS and KTW, BT measured at 3mm apical to the bone crest, and tooth type. This information can be used in the recognition of common periodontal phenotypical patterns associated with specific features of great clinical significance.


Opportunities in the Extended Day: Approaches for Promoting Physical Activity and Healthy Eating During Out-of-School Time.
This systematic review aims to identify out-of-school time (OST) interventions (eg, programming, policies) that increased opportunities for physical activity (PA) and healthy eating and/or improved youth PA and dietary behaviors. We searched for articles within systematic reviews that met our criteria (2010-2018) and for individual articles (2010-2020). Reviewer pairs screened articles, double-extracted data, assessed risk of bias (RoB), and achieved consensus. We included 71 articles (55 studies, 60 intervention arms). Health (n = 3) and nutrition education (n = 7) interventions showed promising results, but most used weak designs and had high RoB. PA-focused interventions (n = 23) were largely consistent in improving fitness and moderate to vigorous PA during programming. Programmatic interventions that improved both PA and nutrition outcomes engaged family or community members (n = 4/13). Most organizational policy interventions improved the nutrition environment and student PA during OST. Organization-level policy and programmatic interventions can improve environmental supports and youth behaviors during OST programming, complementing school-day efforts to address student PA and dietary intake. To maximize their potential impact, OST programs need to be accessible to families. Administrators can consider actions to reduce participation barriers.