Hypoglycemia and antihyperglycemic treatment in adult MODY patients - A systematic review of literature.
Maturity onset diabetes of the young (MODY) is a heterogeneous group of diseases caused by a single mutation in one of the 14 genes involved in the regulation of glucose homeostasis. GCK, HNF1A, and HNF4A genes are among the most common genes affected. Expression of these genes in the key organs for defense against hypoglycemia and their participation in counter-regulation to hypoglycemia may potentially put individuals with a heterozygous mutation in these genes at increased risk for hypoglycemia. In HNF4A-MODY and HNF1A-MODY patients, normal or even increased insulin sensitivity together with glucose-independent mechanism of action of the first-line therapy - sulphonylurea derivatives - often leads to hypoglycemia, even at the much lower dose used in type 2 diabetes. This review aims to analyze clinical studies and case reports concerning hypoglycemia associated with antihyperglycemic treatment in adult MODY patients.


Characterization of proteoglycan 4 and hyaluronan composition and lubrication function of ovine synovial fluid following knee surgery.
The objective of this study was to determine changes in (1) proteoglycan 4 (PRG4) and hyaluronan (HA) concentration, (2) HA molecular weight (MW) distribution, and (3) cartilage boundary lubricating ability of synovial fluid (SF) from surgical sham (SHAM), anterior cruciate ligament (ACL)/medial collateral ligament (MCL) transection, and lateral meniscectomy (MEN) in a post-knee surgery ovine model. Ovine SF (oSF) was collected at euthanization 20 weeks after surgery, with the contralateral joint serving as the non-operative control. PRG4 and HA concentration in oSF was measured by sandwich enzyme-linked immunosorbent assay, and HA MW distribution by agarose gel electrophoresis. Cartilage boundary lubricating ability of oSF was measured by a cartilage-cartilage friction test. PRG4 and HA concentration in SHAM, ACL/MCL, and MEN oSF were similar in comparison to the contralateral control (CTRL) oSF. The HA MW distribution in the operated oSF for all ranges were similar to the respective CTRL oSF. The kinetic coefficients of friction in operated and CTRL oSF were similar in all groups, and were significantly lower than saline. These results indicate oSF lubricant composition and function at 20 weeks post-knee surgery were similar to contralateral CTRL, and suggest earlier time points post surgery warrant further investigation.


Cellular distribution of NKCC2 in the gastric mucosa and its response to short-term osmotic shock.
The Na(+)-K(+)-2Cl(-) cotransporter-2 (NKCC2) has long been recognized as a "kidney-specific" transporter and is important in salt reabsorption. NKCC2 has been found in the gastric mucosa; however, its cellular distribution and function remain obscure. The present study characterized the distribution pattern of NKCC2 in mammalian gastric mucosa and investigated its response to osmotic challenge. Reverse transcription with the polymerase chain reaction, Western blot and immunofluorescence were used to determine NKCC2 expression and localization. The effect of osmotic shock on NKCC2 expression was studied in isolated gastric mucosa with variable osmolarity treatment. Results from all of the above studies were compared with those of NKCC1. Our data indicated that NKCC1 and NKCC2 were expressed in the gastric mucosa of rat, mouse and human. The mRNA transcripts and proteins for NKCC1 and NKCC2 were broadly expressed in the rat gastric mucosa. In rat and mouse, NKCC1 was largely confined to the lower part of the oxyntic and pyloric gland areas, whereas NKCC2 extended throughout the gastric glands. NKCC1 immunoreactivity was strongly expressed in the parietal and chief cells but was weaker in the mucous cells. NKCC2 was abundantly located in the parietal and mucous cells but faintly distributed in the chief cells. Hypertonic treatment increased the protein level of NKCC1 and caused evident membrane translocation. In contrast, NKCC2 was significantly downregulated and no obvious membrane translocation was observed. Thus, NKCC2 displayed a more ubiquitous distribution in the gastric mucosa and might work coordinately with NKCC1 to maintain cell volume homeostasis under hypertonic conditions.


IVUS-guided wiring technique: promising approach for the chronic total occlusion.
We report on two cases of IVUS-guided wiring technique performed on chronic total occlusion using stiffer wires and low-profile intracoronary ultrasound catheter. This technique helped improve a success rate of chronic total occlusion case.


Synthesis and Computational Study of an Optical Fluorescent Sensor for Selective Detection of Ni2+ Ions.
The presence of an abnormal amount of Ni2+ in the human body causes various health issues. Therefore, this work aimed to synthesize the curcumin-based fluorescence-on sensor P [2,6-bis((E)-4-chlorobenzylidene)-cyclohexan-1-one] that was capable of selectively responding to Ni2+ ions in aqueous solution. The structure of P was confirmed by 1H NMR and Fourier transform infrared (FTIR) spectroscopy. The Ni2+ ion sensing was based on the fluorescence enhancement of the fluorophore (P) in neutral aqueous medium. The response of the P-based sensor was highly selective toward Ni2+ ions, whereas the possible interferences from other metal cations were negligible. P had a fast response; it was selective and had a sensitive detection limit (LOD = 2 × 10-10 M) toward Ni2+ ions in neutral medium with a high association constant (K) value of 3.6 × 105 M-2 for the complex formation between the P and Ni2+ ions. Job's plot and DFT calculations proved that the binding stoichiometry of P for Ni2+ was 2:1. P was recovered using EDTA as a chelating agent after being employed as a fluorescent sensor. These characteristics ensured the potential use of P as a new class of chemosensor for environmental applications.


Studies on the mechanisms of the sporicidal action of ortho-phthalaldehyde.
To determine the mechanism of killing of spores of Bacillus subtilis by ortho-phthalaldehyde (OPA), an aromatic dialdehyde currently in use as an antimicrobial agent. OPA is sporicidal, although spores are much more OPA resistant than are vegetative cells. Bacillus subtilis mutants deficient in DNA repair, spore DNA protection and spore coat assembly have been used to show that (i) the coat appears to be a major component of spore OPA resistance, which is acquired late in sporulation of B. subtilis at the time of spore coat maturation, and (ii) B. subtilis spores are not killed by OPA through DNA damage but by elimination of spore germination. Furthermore, OPA-treated spores that cannot germinate are not recovered by artificial germinants or by treatment with NaOH or lysozyme. OPA appears to kill spores by blocking the spore germination process. This work provides information on the mechanism of spore resistance to, and spore killing by, the disinfectant, OPA.


Purification and characterization of novel isoforms of the polyphenol oxidase from Malus domestica fruit pulp.
Polyphenol oxidases (PPOs), belong to the group of oxidoreductases that are copper containing enzymes and are responsible for plant browning. PPOs are extensively distributed in plant kingdom and can oxidize wide range of aromatic compounds of industrial importance. The aim of this study was purification and characterization of PPO isoforms from the fruit pulp of Golden delicious apple. High performance liquid chromatography was used to purify the two novel isoforms of PPO and further their molecular weights (45 and 28 kDa) were determined using sodium dodecyl sulfate polyacrylamide gel electrophoresis. The purified isoforms have optimum pH (6.5), optimum temperature (40°C), the Vmax (4.45 μM/min) and Km (74.21 mM) with catechol substrate. The N-terminal microsequences of both PPO isoforms were determined using a pulse liquid protein sequencer and found to be AKITFHG (28 kDa) and APGGG (45 kDa). Polyphenol oxidases are efficiently used in the pharmaceutical, paper and pulp, textiles and food industries. Recently, the PPOs have been used for bioremediation and in the development of biosensors.


What is the clinical relevance of erosions and joint space narrowing in RA?
The association between joint damage and disability in rheumatoid arthritis (RA), especially in the later stages of disease, is a main reason why radiographic joint damage is a common and valid outcome measure in RA clinical trials. Most studies have assessed the effect of global joint damage, which has limited our knowledge regarding the individual effects of erosions and cartilage damage on physical function. However, recent data have indicated that joint space narrowing is more closely related to functional status than erosions. Modern imaging techniques that provide improved assessment of the cartilage itself, instead of only joint space narrowing, might help disentangle the separate associations of erosive bone damage and cartilage damage with physical function in patients with RA. The aim of this article is to discuss the current knowledge within this field and the clinical consequences thereof.


Asymmetric orientation of the reconstituted aspartate/glutamate carrier from mitochondria.
A partially purified preparation of the aspartate/glutamate carrier from bovine heart mitochondria was reconstituted into liposomal membranes by chromatography on hydrophobic ion exchange resins. Based on the favorable conditions of this reconstituted system the transmembrane orientation of the inserted carrier protein could be determined by functional analysis. For reliable measurement of the reconstituted aspartate-glutamate exchange activity an optimized inhibitor-stop technique using pyridoxal phosphate was developed. By simultaneous application of both forward and backward exchange experiments the practical usefulness of the reconstituted system could be extended to investigations including variation of internal and external substrate concentrations over a wide range. Thereby a complete set of Km values for both aspartate and glutamate at both the internal and external side of the proteoliposomes could be established. These experiments led to the following results and conclusions: (i) The observed substrate affinities are clearly different for the two different membrane sides both for aspartate (external 50 microM, internal 3 mM) and glutamate (external about 200 microM, internal 3 mM). (ii) The exclusive presence of only one type of transport affinity for every single substrate at one side of the liposomal membrane clearly demonstrates the asymmetric orientation of the functionally active carrier protein molecules. (iii) When comparing the values of these constants with published data obtained in mitochondria, an inside-out orientation of the aspartate/glutamate carrier after isolation and reinsertion into liposomes is strongly suggested.


[Hepatography in the course of lymphography].
Two cases are presented in which epatography occurred following lymphangiography. The morphologic findings and their changes in subsequent controls are described. Attention is pointed on the uncommon persistance of epatography for a few months from lymphangiography.


The Nexus Between High-Involvement Work Practices and Employees' Proactive Behavior in Public Service Organizations: A Time-Lagged Moderated-Mediation Model.
Public service organizations may improve the quality of services they offer citizens by instilling proactive behavior in their employees. This study aimed to provide insights on how high-involvement work practices may indirectly facilitate proactive behavior in frontline government employees via employee commitment. A time-lagged approach was used to collect data from 542 frontline employees in three waves at 3-week intervals. We tested the hypothesized moderated mediation model using a PROCESS macro bootstrap approach. A moderated-meditation model was applied in which public service motivation was theorized to increase the mediating effect of employee commitment on the relationship between high-involvement work practices and employee proactive behavior. As predicted, the findings show that supervisor' deviant behavior attenuated the mediating effect of employee commitment on the relationship between high-involvement work practices and employee proactive behavior. The findings of this research contribute to the emerging literature on public management and have implications for public sector organizations seeking to improve the quality of services they offer citizens.


Meta-analysis of clinical trials based on censored end-points: simplified theory and implementation of the statistical algorithms on a microcomputer.
Meta-analysis is increasingly being used in clinical research. While the meta-analytical algorithms for pooling the results of studies using non-censored end-points are now sufficiently standardized, the management of trials based on censored end-points is still controversial, and specific algorithms of meta-analysis are still needed (for example, censored end-points are commonly used in survival studies of cancer patients). In the present article we review the various algorithms that have thus far been utilized to perform a meta-analysis based on censored end-points, and we propose a new and original approach that combines two of the existing algorithms. Our approach is designed to formulate any meta-analysis of survival studies in terms of the calculation of an odds ratio. The meta-analytical odds ratio proposed here is called the 'log-rank' odds ratio of meta-analysis. A microcomputer program is described that implements the various methods of meta-analysis that can handle clinical trials based on censored end-points. Some examples are presented to illustrate the use of the program.


Effects of ionizing radiation on woven bone: influence on the osteocyte lacunar network, collagen maturation, and microarchitecture.
Evaluate the effects of ionizing radiation on microarchitecture, the osteocyte lacunar network, and collagen maturity in a bone repair site. Bone defects were created on tibias of 20 New Zealand rabbits. After 2 weeks, the animals were randomly divided into (n = 10) NoIr (nonirradiated group) and Ir (irradiated group). In the Ir, the animals received single-dose irradiation of 30 Gy on the tibia and were euthanized after 2 weeks. Bone microarchitecture parameters were analyzed by using micro-CT, and the osteocyte lacunar network, bone matrix, and collagen maturation by histomorphometric analysis. The data were analyzed using unpaired Student's t test (α = 0.05). Trabecular thickness in Ir was lower than that in NoIr (P = 0.028). No difference was found for bone volume fraction and bone area. Lacunae filled with osteocytes were more numerous (P < 0.0001) in NoIr (2.6 ± 0.6) than in Ir (1.97 ± 0.53). Empty lacunae were more prevalent (P < 0.003) in Ir (0.14 ± 0.10) than in NoIr (0.1 ± 0.1). The mean osteocyte lacunae size was higher (P < 0.01) in Ir (15.4 ± 4.41) than in NoIr (12.7 ± 3.7). Picrosirius red analysis showed more (P < 0.05) mature collagen in NoIr (29.0 ± 5.3) than in Ir (23.4 ± 4.5). Immature collagen quantification revealed no difference between groups. Ionizing radiation compromised bone formation and an impairment in bone repair in irradiated woven bone was observed. Before radiotherapy, patients usually need surgical intervention, which may be better performed, if clinicians understand the repair process in irradiated bone, using novel approaches for treating these individuals.


Structural and functional properties of different types of siphonous LHCII trimers from an intertidal green alga Bryopsis corticulans.
Light-harvesting complexes of photosystem II (LHCIIs) in green algae and plants are vital antenna apparatus for light harvesting, energy transfer, and photoprotection. Here we determined the structure of a siphonous-type LHCII trimer from the intertidal green alga Bryopsis corticulans by X-ray crystallography and cryo-electron microscopy (cryo-EM), and analyzed its functional properties by spectral analysis. The Bryopsis LHCII (Bry-LHCII) structures in both homotrimeric and heterotrimeric form show that green light-absorbing siphonaxanthin and siphonein occupied the sites of lutein and violaxanthin in plant LHCII, and two extra chlorophylls (Chls) b replaced Chls a. Binding of these pigments expands the blue-green light absorption of B. corticulans in the tidal zone. We observed differences between the Bry-LHCII homotrimer crystal and cryo-EM structures, and also between Bry-LHCII homotrimer and heterotrimer cryo-EM structures. These conformational changes may reflect the flexibility of Bry-LHCII, which may be required to adapt to light fluctuations from tidal rhythms.


Proteomics analysis of contact-initiated eph receptor-ephrin signaling.
Large-scale biochemical analysis of cell-specific signaling can be interrogated in cocultures of Eph receptor- and ephrin-expressing cells by combining proteomics analysis with cell-specific metabolic labeling. In this chapter, we describe how to perform such large-scale analysis, including the generation of cells stably expressing the receptors and ligands of interest, optimization steps for Eph-ephrin coculture, and the proteomics analysis. As the experimental details may vary depending on the specific system that is being interrogated, the goal of the chapter is mainly to provide sufficient experimental context for experienced researchers to set up and conduct these experiments.


Correlates of adult and child perceptions of social competency.
In this study, the relationship between two commonly used measures of social competency, peer ratings of perceived status and adult ratings of assertiveness, were examined. In Phase I, high and low sociometric status children were videotaped responding to a series of role-play scenes; performance on these scenes was then rated retrospectively by adults for overall assertiveness. In Phase II, a second group of children who were unfamiliar with the videotaped children observed the taped scenes and provided ratings of likability, intelligence, working together, and attractiveness. In general, results revealed that children and adults differed in their ratings of the videotaped children. Further, boys used different cues in their ratings than did girls. More specifically, the sociometric status of girls was related to perceived attractiveness, whereas the sociometric status of boys was more closely related to perceived intelligence. Such findings suggest that children and adults look for and use different cues in their judgments. Given these differences, it is concluded that child and adult ratings should not be used interchangeably in the assessment of, and evaluation of, social competency in children.


Experimental approaches to treatment of soft tissue sarcoma.
The experimental approaches described in this article represent potential new approaches for targeted therapy. Thus far, none of the preclinical data have demonstrated a cure for sarcomas; however, the antitumor effects of many of these new agents seem to be enhanced when the agents are combined with chemotherapeutic agents. The combination of novel therapeutics with conventional chemotherapy may be the most effective strategy in terms of maximization of tumor killing and minimization of toxicity and the risk of drug resistance. Not only are new drugs being developed for treatment of sarcomas but new ways of delivering drugs are also being investigated. The angiogenic, or metronomic, schedule of drug delivery may be preferable to conventional schedules in achieving optimal tumor inhibition. In addition, isolated limb perfusion is a unique approach to delivery of drugs, such as TNF and melphalan, for sarcomas and melanomas [137, 138]. The advantages of this method of drug delivery include the ability to administer therapeutic agents in high concentrations to a specific region of the body without systemic toxicity. Further advances in the understanding of the biology of sarcomas along with novel approaches to delivery of drugs are crucial to the development of new and effective therapies.


Linking paranormal and conspiracy beliefs to illusory pattern perception through signal detection theory.
Previous research indicates that irrational beliefs (Paranormal beliefs & conspiracy theory endorsement) are associated with the perception of patterns in noise, but the previous findings do not conclusively describe this relationship. This study aims to disentangle the underlying parameters of this association by applying a signal detection theory approach, thus allowing to distinguish illusory pattern perception (false alarms) from perceptual sensitivity and response tendencies-while also taking base rate information into account. Results from a large sample (N = 723) indicate that paranormal beliefs relate to a more liberal response bias and a lower perceptual sensitivity, and that this relationship is driven by illusory pattern perception. Such a clear pattern could not be observed for conspiracy beliefs, for which the increase in false alarm rates was moderated by the base rate. The associations between irrational beliefs and illusory pattern perception were however less substantial compared to other sources of variance. Implications are discussed.


Molecular mechanisms of calcium-dependent neurodegeneration in excitotoxicity.
Excitotoxicity contributes to neuronal degeneration in many acute CNS diseases, including ischemia, trauma, and epilepsy, and may also play a role in chronic diseases, such as amyotrophic lateral sclerosis (ALS). Key mediators of excitotoxic damage are Ca ions (Ca(2+)), which under physiological conditions govern a multitude of cellular processes, including cell growth, differentiation, and synaptic activity. Consequently, homeostatic mechanisms exist to maintain a low intracellular Ca(2+) ion concentration so that Ca(2+) signals remain spatially and temporally localized. This permits multiple independent Ca-mediated signaling pathways to occur in the same cell. In excitotoxicity, excessive synaptic release of glutamate can lead to the disregulation of Ca(2+) homeostasis. Glutamate activates postsynaptic receptors, including the ionotropic N-methyl-D-aspartate (NMDA), 2-amino-3-(3-hydroxy-5-methylisoxazol-4-yl) proprionate (AMPA), and kainate receptors. Upon their activation, these open their associated ion channel to allow the influx of Ca(2+) and Na(+) ions. Although physiological elevations in intracellular Ca(2+) are salient to normal cell functioning, the excessive influx of Ca(2+) together with any Ca(2+) release from intracellular compartments can overwhelm Ca(2+)-regulatory mechanisms and lead to cell death. Although Ca(2+) disregulation is paramount to neurodegeneration, the exact mechanism by which Ca(2+) ions actually mediate excitotoxicity is less clear. One hypothesis outlined in this review suggests that Ca(2+)-dependent neurotoxicity occurs following the activation of distinct signaling cascades downstream from key points of Ca(2+) entry at synapses, and that triggers of these cascades are physically co-localized with specific glutamate receptors. Thus, we summarize the importance of Ca(2+) regulation in mammalian neurons and the excitotoxicity hypothesis, and focus on the molecular determinants of glutamate receptor-mediated excitotoxic mechanisms.


Two-dimensional vibrationally driven solid particle structures in non-uniformly heated fluid containers.
Building on a pre-existing line of inquiry where the presence of solid particle attractors in thermovibrationally driven flows was demonstrated in cavities subjected to a unidirectional temperature gradient, the present work considers cases where the direction of such a gradient is allowed to change inside the fluid. Moreover, the considered configurations differ with regard to the angle that vibrations form with respect to a reference axis. Variations in the orientation of the temperature gradient are made possible by setting a non-uniform temperature distribution along certain walls. The relationship between the multiplicity (N) of the loci of particle attraction and the inhomogeneities in the temperature field is studied. It is shown that N can exceed the limit N = 2 found in earlier studies and that a zoo of new particle accumulation structures show up, whose ranges of existence depend on the amplitude and frequency of vibrational acceleration, the particle Stokes number, the orientation of vibrations, and the number of inversions in the direction of the temperature gradient.


Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19.
We previously reported inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity in 1-5% of unvaccinated patients with life-threatening COVID-19, and auto-antibodies against type I IFN in another 15-20% of cases. We report here a genome-wide rare variant burden association analysis in 3,269 unvaccinated patients with life-threatening COVID-19 (1,301 previously reported and 1,968 new patients), and 1,373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. A quarter of the patients tested had antibodies against type I IFN (234 of 928) and were excluded from the analysis. No gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7 , with an OR of 27.68 (95%CI:1.5-528.7, P= 1.1×10 -4 ), in analyses restricted to biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70 [95%CI:1.3-8.2], P= 2.1×10 -4 ). Adding the recently reported TYK2 COVID-19 locus strengthened this enrichment, particularly under a recessive model (OR=19.65 [95%CI:2.1-2635.4]; P= 3.4×10 -3 ). When these 14 loci and TLR7 were considered, all individuals hemizygous ( n =20) or homozygous ( n =5) for pLOF or bLOF variants were patients (OR=39.19 [95%CI:5.2-5037.0], P =4.7×10 -7 ), who also showed an enrichment in heterozygous variants (OR=2.36 [95%CI:1.0-5.9], P =0.02). Finally, the patients with pLOF or bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P= 1.68×10 -5 ). Rare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old.


Developing and testing inter-rater reliability of a data collection tool for patient health records on end-of-life care of neurological patients in an acute hospital ward.
Develop and test a data collection tool-Neurological End-Of-Life Care Assessment Tool (NEOLCAT)-for extracting data from patient health records (PHRs) on end-of-life care of neurological patients in an acute hospital ward. Instrument development and inter-rater reliability (IRR) assessment. NEOLCAT was constructed from patient care items obtained from clinical guidelines and literature on end-of-life care. Expert clinicians reviewed the items. Using percentage agreement and Fleiss' kappa we calculated IRR on 32 nominal items, out of 76 items. IRR of NEOLCAT showed 89% (range 83%-95%) overall categorical percentage agreement. The Fleiss' kappa categorical coefficient was 0.84 (range 0.71-0.91). There was fair or moderate agreement on six items, and moderate or almost perfect agreement on 26 items. The NEOLCAT shows promising psychometric properties for studying clinical components of care of neurological patients at the end-of-life on an acute hospital ward but could be further developed in future studies.


The antimitogenic action of the sulphated polysaccharide fucoidan differs from heparin in human vascular smooth muscle cells.
The sulphated polysaccharides fucoidan and heparin both inhibit vascular smooth muscle cell (VSMC) proliferation. In this study we compared their actions on mitogenesis and ERK1/ERK2 activation in human VSMC. Although they displaced cell surface [3H]-heparin binding with similar affinity, they exerted clearly distinguishable actions. Fucoidan potently inhibited DNA synthesis stimulated by foetal calf serum, PDGF-BB and thrombospondin-1. Heparin inhibited the mitogenic action of serum and thrombospondin- I (though less potently than fucoidan), but failed to inhibit PDGF-BB-induced DNA synthesis. In parallel studies, fucoidan, but not heparin, inhibited ERK1/ERK2 activation by PDGF-BB. Moreover, fucoidan inhibited serum-induced mitogenesis in "heparin resistant" VSMC, which are refractory to heparin's antimitogenic action. In summary, the structurally different polysaccharides, heparin, fucoidan (and fucans) have distinguishable effects on mitogenesis and ERK1/ERK2 activation, suggesting that different mechanism(s) mediate these actions. The potent antimitogenic action of fucoidan and its efficacy in heparin resistant VSMC emphasise the need to further investigate its mechanism of action in human VSMC and suggest this agent could have therapeutic potential.


Radon emanation measurements using silicon photodiode detectors.
Driven by the global concern about radon hazards, a wide variety of methods to measure radon and its decay products have been developed. Pin silicon photodiodes are increasingly applied in this field, their main advantages being high detection efficiency for alpha particles and low cost. In this paper, we present a system to determine the emanation factor for 222Rn from porous material based on a pin photodiode. This equipment is valid both for field and laboratory measurements, allowing to monitor the external emanation conditions by means of temperature, humidity and pressure sensors. To illustrate the capabilities of the system, we present two case studies of samples with high and low 226Ra content. The activity of this radionuclide in the samples had been previously determined by gamma-ray spectrometry.


Haematology, genotoxicity, enzymatic activity and histopathology as biomarkers of metal pollution in the shrew Crocidura russula.
Haematological (WBC, RBC, Hgb and Hct) and genotoxicity (MNT) parameters, hepatic enzymatic activities (GST, GPx and GR), and a histopathological evaluation of liver, kidneys and gonads were assessed as general biomarkers of metal pollution in the shrew Crocidura russula inhabiting a pyrite mining area. Specimens exposed to metals presented a few significant alterations when compared with reference animals: GST activity decreased; micronuclei increased; and evident liver alterations related to metal exposure were observed. On the basis of all the parameters studied, age was an important factor that partly explained the observed variation, whereas sex was the least important factor. Significant correlations were also found between heavy metal concentrations and biomarkers evaluated, demonstrating the great influence of these metals in the metabolic alterations. To the best of our knowledge, these data constitute the first measurements of a battery of biomarkers in shrews from a mine site and are among the few available for insectivorous mammals.


Epigenome dynamics: a quantitative genetics perspective.
Classically, quantitative geneticists have envisioned DNA sequence variants as the only source of heritable phenotypes. This view should be revised in light of accumulating evidence for widespread epigenetic variation in natural and experimental populations. Here we argue that it is timely to consider novel experimental strategies and analysis models to capture the potentially dynamic interplay between chromatin and DNA sequence factors in complex traits.


The cadmium-induced disruption of tight junctions in LLC-PK1 cells does not result from apoptosis.
Exposure of LLC-PK1 cells to low micromolar concentrations of Cd2+ for 1-4 hours causes the disruption of the adhering and occluding junctions between the cells, whereas exposure to higher concentrations of Cd2+ for longer periods of time causes more severe toxic effects and cell death. The objective of the present studies was to determine whether or not the junctional effects of Cd2+ might be a consequence of apoptotic injury. LLC-PK1 cells on cell culture inserts were exposed to either Cd2+ or tumor necrosis factor (TNF-alpha) plus cycloheximide, a treatment that has recently been shown to cause apoptosis in LLC-PK1 cells. The results showed that at the time the Cd2(+)-induced junctional changes were occurring, there was no increase in the number of apoptotic cells or evidence of DNA fragmentation. By contrast, TNF-alpha plus cycloheximide induced changes that were characteristic of apoptosis. These results indicate that the disruption of intercellular junctions by Cd2+ in the LLC-PK1 cell line occurs independently of apoptosis.


Surfing the piperazine core of tricyclic farnesyltransferase inhibitors.
In order to fully explore structure-activity relationships at the 1- and 2-positions of the piperazine core of tricyclic farnesyltransferase inhibitors, an 11,718-member ECLiPS library was synthesized and screened in a farnesyltransferase scintillation proximity assay. A detailed description of the library and analyses of the screening data will be provided.


Postoperative high-dose-rate brachytherapy in the prevention of keloids.
The aim of this study is to show the efficiency of keloidectomy and postoperative interstitial high-dose-rate (HDR) brachytherapy in the prevention of keloids. Between 1998 and 2004, 35 patients with 54 keloids were treated postoperatively with HDR brachytherapy. The first HDR dose was applied within 6 hours after surgery, and two additional HDR doses were administered on the next day with a six-hour interval. The majority of patients received 6 Gy as the first dose postsurgery and two fractions of 4 Gy (38 keloids) on the next day. Seven keloids were treated postoperatively with three fractions of 6 Gy. The biologically effective dose (BED), derived from the linear quadratic concept, was applied to calculate the BED for the various radiation regimens. The keloid recurrence rates at specific BED values were compared with those derived for other fractionation schemes in the literature. Four recurrences/nonsatisfactory results out of nine treated keloids were observed after treatments with 1 x 4 Gy + 2 x 3 Gy. Only one recurrence out of 38 was found after 1 x 6 Gy + 2 x 4 Gy and none after 3 x 6 Gy. Better cosmetic results were found at the higher-dose schemes. The results of this study prove the effectiveness of HDR brachytherapy after keloidectomy provided that the total HDR dose is sufficient. Currently our scheme is 3 x 6 Gy.


Grafting homogenous electrochemical biosensing strategy based on reverse proximity ligation and Exo III assisted target circulation for multiplexed communicable disease DNA assay.
Rapid and effective diagnosis of communicable disease is one of the critical issues of the modern society, especially for detecting different targets at the same time. In this work, a grafting homogenous electrochemical biosensing strategy is proposed by integrating of reverse proximity ligation and exonuclease III (Exo III) assisted target circulation to analyze hepatitis B (HBV) and human immunodeficiency (HIV). Specially, a two-wing nanodevice (TWD) with two detection paths is elaborately designed based on analogous proximity ligation assay. The reverse proximity ligation process provides a new way of signal conversion and amplification, what accomplished by demolishing the TWD in the presence of targets. Meanwhile, a vast number of signal probes are released via Exo III assisted target circulation. Then the signal probes are grafted on the universal sensing interface, which is decorated with graftable tetrahedron DNA (GTD). These lead to a highly amplified electrochemical signal. Compared with the conventional strategies, the grafting homogenous electrochemical biosensing strategy not only achieves convenient sensitive detection of multiple communicable diseases DNA simultaneously, but also performs well in the detection of sole target. This strategy effectively decreases the background, homogenizes the distribution of probes, and avoids the complex and time-consuming modification process of the working electrode, which holds great potential application in early diagnosis for communicable disease in the future.


Efficacy of Quercetin as a potent sensitizer of β2-AR in combating the impairment of fluid clearance in lungs of rats under hypoxia.
Hypoxia reportedly increases free radical generation in the body, causing oxidative stress and inhibiting β2-AR signaling. The present study correlates the prophylactic potential of quercetin and salbutamol in ameliorating fluid clearing capacity of lungs by re-sensitizing β2-AR signaling under hypoxia. Male SD rats supplemented orally with quercetin (50 mg/Kg BW), and salbutamol (2 mg/Kg BW) were exposed to hypobaric hypoxia at 7620 m for 6 h. Western blotting and ELISA quantitated NFĸB and related genes and GPCR pathway proteins. The binding affinities of drugs with receptor were determined by SPR spectroscopy and further confirmed insilico. Quercetin and salbutamol pre-treatment significantly up-regulated the expressions of β2-AR, GPR-1, GPR-10, GCSα, cAMP content, and down-regulated GRK-2, β-arrestin, ROS, NFκB (p < 0.001), thus, enhancing alveolar fluid clearance (AFC). SPR and insilico findings revealed a higher binding affinity of β2-AR with quercetin over salbutamol. Results indicated quercetin to be a better prophylactic that augmented AFC in rats exposed to hypoxia by attenuating inflammation and stimulating β2-AR.


In Vivo Analysis of Heterogeneous Extracellular Vesicles Using a Red-Shifted Bioluminescence Resonance Energy Transfer Reporter Protein.
Current methods for characterizing the biodistribution of extracellular vesicles (EVs) are not sensitive enough to track EVs in vivo, despite significant advances over the past decade. Commonly used lipophilic fluorescent dyes are convenient, but lack specificity and yield inaccurate spatiotemporal images in the long-term tracking of EVs. In contrast, protein-based fluorescent or bioluminescent EV reporters have more accurately revealed their distribution in cells and mouse models. Here, we describe a red-shifted bioluminescence resonance energy transfer (BRET) EV reporter, PalmReNL, to analyze the trafficking of small EVs (<200 nm; sEVs) and medium/large EVs (>200 nm; m/lEVs) in mice. Its advantages are that (i) background signals in bioluminescence imaging (BLI) are negligible and (ii) the photons PalmReNL emits have spectral wavelengths longer than 600 nm and can more efficiently penetrate tissues than reporters emitting shorter wavelength light.


Clinical progression of incidental tomographic findings in paranasal sinuses of asymptomatic individuals: cohort study.
To determine whether the presence of opacification in the paranasal sinuses of children and adolescents without rhinosinusitis implies an increased risk of later development of upper respiratory tract symptoms. This was a prospective study of a cohort of patients aged 0 to 18 years who underwent computerized tomography (CT) scans for indications unrelated to rhinosinusitis. Sinus opacification was evaluated using an opacification/development ratio score. The patients' clinical progression was followed up using a questionnaire for 1 month after the scans. Fifty-six percent (56%) of the 106 patients enrolled in the study had opacity, the majority due to mucosal thickening. Intense opacification was defined as "suspected" (score ≥ 15) and patients in this subset had a greater risk of developing symptoms during follow-up (odds ratio = 2.74; 95%CI 1.10-6.83) compared to those with no findings or discrete findings. Intense incidental sinus opacity on CT indicates a risk of future development of a clinical respiratory condition.


Hepatocellular carcinoma targeting effect of PEGylated liposomes modified with lactoferrin.
A hepatocellular carcinoma targeting lactoferrin (Lf) modified PEGylated liposome system was developed for improving drug efficacies to hepatic cancer cells. In this present work, PEGylated liposomes (PLS) were successfully prepared by the thin film hydration method combined with peglipid post insertion. Lf was covalently conjugated to the distal end of DSPE-PEG2000-COOH lipid by amide bound and loaded onto PEGylated liposomes surface as the targeting ligand. To confirm the targeting efficacies to hepatic cancer, coumarin-6 and DiR were encapsulated as fluorescent probes. The confocal microscopy and flow cytometry demonstrated that Lf conjugated PEGylated liposomes (Lf-PLS) were efficiently associated by HepG2 cells, while limited interaction was found for liposomes modified with a negative control protein. A similar pharmacokinetic behavior was observed in pharmacokinetics study of the liposomal formulations. Meanwhile, the in vivo imaging of liposomes in HepG2 tumor bearing mice indicated that Lf-PLS achieved more accumulation in tumor compared with PLS without Lf conjugated. The significant in vitro and in vivo results suggested that Lf-PLS might be a promising drug delivery system for hepatocellular carcinoma therapy with low toxicity.


Rats with different thresholds to clonic convulsions induced by DMCM differ in the binding of [3H]-MK-801 and [3H]-ouabain in the membranes of brain regions.
Considering the putative participation of N-methyl-D-aspartate (NMDA) receptors and the Na(+), K(+)-ATPase enzymes in the susceptibility to convulsions induced by the benzodiazepine inverse agonist methyl 6,7-dimethoxy-4-ethyl-β-carboline-3-carboxylate (DMCM), the present study sought to determine if rats with high (HTR) and low (LTR) thresholds to clonic convulsions induced by DMCM differed in the following aspects: the binding of NMDA receptors by [(3)H]-MK-801, Na(+), K(+)-ATPase activity (K(+)-stimulated p-nitrophenylphosphatase) and high-affinity [(3)H]-ouabain binding to membranes from discrete brain regions. Compared to the HTR subgroup, the LTR subgroup presented a lower binding of [(3)H]-MK-801 in the hippocampus, frontal cortex and striatum. The subgroups did not differ in K(+)-p-nitrophenylphosphatase activity, but the LTR subgroup had a lower density of isozymes with a high-affinity to ouabain in the brainstem and in the frontal cortex and a lower affinity to ouabain in the hippocampus than the HTR subgroup. These results suggest that NMDA receptors and ouabain-sensitive Na(+), K(+)-ATPase isozymes may underlie the susceptibility to DMCM-induced convulsions.


Localized controlled release of bevacizumab and doxorubicin by thermo-sensitive hydrogel for normalization of tumor vasculature and to enhance the efficacy of chemotherapy.
In a malignant tumor, overexpression of pro-angiogenic factors like vascular endothelial growth factor (VEGF) provokes the production of pathologic vascular networks characterized by leaky, chaotically organized, immature, thin-walled, and ill-perfused. As a result, hostile tumor environment would be developed and profoundly hinders anti-cancer drug activities and fuels tumor progression. In this study, we develop a strategy of sequential sustain release of anti-angiogenic drug, Bevacizumab (BVZ), and anti-cancer drug, Doxorubicin (DOX), using poly (d, l-Lactide)- Poly (ethylene glycol) -Poly (d, l-Lactide) (PDLLA-PEG-PDLLA) hydrogel as a local delivery system. The release profiles of the drugs from the hydrogel were investigated in vitro which confirmed that relatively rapid release of BVZ (73.56 ± 1.39%) followed by Dox (61.21 ± 0.62%) at pH 6.5 for prolonged period. The in vitro cytotoxicity test revealed that the copolymer exhibited negligible cytotoxicity up to 2.5 mg ml-1 concentration on HaCaT and HeLa cells. Likeways, the in vitro degradation of the copolymer showed 41.63 ± 2.62% and 73.25 ± 4.36% weight loss within 6 weeks at pH 7.4 and 6.5, respectively. After a single intratumoral injection of the drug-encapsulated hydrogel on Hela xenograft nude, hydrogel co-loaded with BVZ and Dox displayed the highest tumor suppression efficacy for up to 36 days with no noticeable damage on vital organs. Therefore, localized co-delivery of anti-angiogenic drug and anti-cancer drug by hydrogel system may be a promising approach for enhanced chemotherapeutic efficacy in cancer treatment.


Pattern of systemic lupus erythematosus in NIGERIA: a multicentre descriptive hospital-based study.
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease with manifestations ranging from mild to life-threatening organ dysfunction. There is wide variability in the reported incidence and prevalence rate globally, particularly in low and middle-income countries. Nigeria had very few isolated reports of SLE from private and public hospitals Therefore, we conducted this large multi-center descriptive study to determine the sociodemographic, clinical profile, laboratory patterns, and treatment among Nigerian lupus patients. A retrospective hospital-based study of all SLE patients seen over 4 years (January 2017 to December 2020) was conducted at 20 rheumatology clinics spread across the 6 geopolitical zones of Nigeria. All patients 18 years and above satisfying the American College of Rheumatology (ACR) 1997 and/or the Systemic Lupus International Collaboration Clinics (SLICC) 2012 classification criteria for SLE were enrolled. Patients with other Rheumatic and Musculoskeletal Diseases (RMDs) not in keeping with SLE and Patients with incomplete data were excluded. Data was analysed using SPSS version 23.0 software. A total of 896 patients with SLE were included in the final analysis with a mean age ± SD of 34.47 ± 11 and a female to male ratio of 8.1:1. Synovitis was reported by 61.6% of patients, while 51%, 19.9% and11.4% patients reported acute, sub-acute and chronic lupus rashes respectively. ANA was positive in 98.0% with titers ranging from 1:80 to 1:64,000. SLE is not rare in Nigeria. Most patients were female in their 3rd to 4th decades of life. There is a delayed presentation to a rheumatology facility. Arthritis and mucocutaneous manifestations were the most frequent presentation. Key Points •This study presents the first national data on SLE in Nigeria •This study showed that SLE is not rare in Nigeria in contrast to previous reports •There appear to be ethnic disparity in the frequency of lupus among Nigerians •Nigerians with lupus have very high titer of ANA.


High dose dexamethasone in high pain responders undergoing total hip arthroplasty: A randomized controlled trial.
Postoperative pain after total hip arthroplasty (THA) may delay postoperative mobilization and discharge. Postoperative pain has been shown to be higher in pain catastrophisers and patients receiving opioids. A single dose of glucocorticoid reduces pain after THA, and an increased dose of glucocorticoids has been found to be effective in patients at high risk of postoperative pain after total knee arthroplasty (TKA), however, the ideal dose in THA remains unknown. To evaluate the effect of a high dose (1 mg kg -1 ) vs. intermediate dose (0.3 mg kg -1 ) of dexamethasone on pain after THA. A randomized double-blind controlled study. A two-centre study including two large arthroplasty sites in Denmark was conducted from February 2019 to August 2020. A total of 160 patients undergoing THA by neuraxial block with multimodal analgesia, having a Pain Catastrophising Scale score >20 and/or preoperative opioid use were included. Patients were randomly assigned to receive dexamethasone 1 mg kg -1 or 0.3 mg kg -1 before THA. Primary outcome was percentage of patients experiencing moderate to severe pain (visual analogue scale, VAS > 30 mm on a 0 to 100 mm scale) on ambulating 24 h after surgery. Secondary outcomes included cumulated pain scores, C-reactive protein (CRP), opioid use, postoperative recovery scores, length of stay, complications, and re-admission within 30 and 90 days. No difference was found in percentage of VAS >30 mm 24 h after surgery in the 5-m walk test (VAS > 30/VAS ≤ 30%); 33/42 (44%) vs. 32/43 (43%), relative risk = 1.04 (95% confidence interval 0.72-1.51; P = 0.814) in 1 mg kg -1vs. 0.3 mg kg -1 respectively. No differences were found in CRP and opioid use between groups. Also, no intergroup differences were found in recovery scores, re-admissions, or complications. 1 mg kg -1vs. 0.3 mg kg -1 dexamethasone improved neither postoperative pain nor recovery in THA in a cohort of predicted high pain responders. ClinicalTrials.gov ID-number NCT03763760 and EudraCT-number 2018-2636-25.


Membrane pathways for water and solutes in the toad bladder: I. Independent activation of water and urea transport.
Vsopressin activates a number of transport systems in the toad bladder, including the systems for water, urea, sodium, and other small solutes. Evidence from experiments with selective inhibitors indicates that these transport systems are to a large extent functionally independent. In the present study, we show that the transport systems can be separately activated. Low concentrations of vasopressin (1 mU/ml) activate urea transport with virtually no effect on water transport. This selective effect is due in part to the relatively greater inhibitor action of endogenous prostaglandins on water transport. Low concentrations of 8-bromoadenosine cyclic AMP, on the other hand, activate water, but not urea transport. In additional experiments, we found that varying the ratio of exogenous cyclic AMP to theophylline activated water or urea transport selectively. These studies support the concept of independently controlled systems for water and solute transport, and provide a basis for the study of individual luminal membrane pathways for water and solutes in the accompanying paper.


Bicarbonate effects, electromotive forces and potassium effluxes in rabbit and guinea-pig gall-bladder.
The stimulating effect of external HCO3- on Na+ salt transport has been examined in rabbit and guinea-pig gall-bladder by electrophysiological methods, as a sequel to a previous study carried out by radiochemical techniques. At steady state, cell K+ activity was found to be significantly reduced in the presence of HCO3-, whereas cell Na+ activity significantly increased; in parallel the apical membrane p.d. was depolarized; K+ equilibrium potential was higher than membrane p.d. in every case. The apical p.d. dependence on K+ was unaffected by HCO3-, but in the guinea-pig it was affected by Cl-. Rapid increases in HCO3- concentration on the luminal side caused a depolarization of the apical p.d. of the guinea-pig within about 30 sec, an effect that did not occur if the tissue was pre-treated with 10(-4) M-acetazolamide; the epithelial resistance and apical/basolateral resistance ratio were unchanged in all cases. The primary action of HCO3- is confirmed to be on the apical membrane; an HCO3- conductance does not seem to be present at this level, either in the rabbit or guinea-pig, nor does HCO3- affect Na+ influx through the apical conductive pathway, so that all the stimulating effects of the anion are confirmed to be on the neutral transports of Na+ salts; in spite of this, the apical electromotive force is modified due to the changed cell K+ activity. The rapid depolarization caused by the anion in the guinea-pig is in agreement with an HCO3- electrogenic secretion and/or a basolateral conductance for the anion. Polyelectrolyte dissociation from protons increases in the absence of external HCO3-: the negative charges are mainly counterbalanced by bound Na+ in the rabbit and by free K+ in the guinea-pig. K+ leakage from the cell into the lumen is calculated to be minimal in the rabbit and all K+ lost could be reabsorbed through the paracellular pathways; K+ efflux to the subepithelial layer via conductive routes is insufficient to account for the over-all K+ efflux.


[The father's depression and emotional functioning of his child with intellectual disability].
The results of numerous researches indicated an interdependence between parent's depressiveness and difficulties in adaptation in children. The aim of this research was to find an answer to the question--whether the depressiveness in the fathers having an influence on the emotional functioning (depressiveness and anxiety) of the child with intellectual disability. The subjects were fathers and their children with intellectual disability. The Beck Depression Inventory and The Children's Depression Inventory M. Kovacs were used. The results indicated clearly that father's depressiveness exerts influence on the rate of depression in children with intellectual disability. Father's level of depressiveness had influence on dysphonic mood, interpersonal problems and anhedonia, negative self-esteem in children with intellectual disability.


Ductal carcinoma in situ of the breast: results of treatment by conservative surgery and definitive irradiation.
To determine local control, survivorship, and cosmesis in women with ductal carcinoma in situ treated by conservative surgery and radiation therapy. We retrospectively analyzed the results of treatment in 56 women with in situ carcinoma of the breast, treated between 1976 and 1990 by conservative surgery and irradiation. Two women had bilateral tumors, for a total of 58 breasts at risk. All patients underwent gross excision of the tumor followed by radiation to the entire breast and a sequential boost to the tumor bed. Eight of the 21 evaluable tumors (38%) had inadequate pathologic margins at the time of excision. Routine re-excision was not performed. The median dose to the whole breast and primary tumor site was 5000 cGy and 6940 cGy, respectively. Median follow-up was 61 months (range 27-191 months). Five patients (9%) failed in the breast for an 8-year actuarial local failure rate of 11%. Median time to failure was 34 months. All five patients with local recurrence underwent mastectomy and are alive, without evidence of disease at a mean of 40 months post mastectomy. The 8-year actuarial absolute and cause specific survivals were 89% and 100%, respectively. Cosmetic results were excellent or totally acceptable in 90% of patients. Patients with ductal carcinoma in situ treated by excision and irradiation achieved acceptable local control and excellent survival and cosmetic results. Because of the long time course associated with local failure, diligent and protracted follow-up is mandatory.


Restricter anorexia nervosa in a thirteen-year-old sheltered Muslim girl raised in Lahore, Pakistan: developmental similarities to westernized patients.
An academically perfectionistic and interpersonally compliant 13-year-old girl raised in a traditional, sheltering Muslim home in Lahore, Pakistan developed restricter anorexia nervosa in the context of being teased about her weight by her closest friend and younger brother, and in a context of family weight preoccupation. Similarities to current pathogenetic hypotheses among Western adolescents are discussed.


Splanchnic venous thrombosis in a nephrotic patient following COVID-19 infection: a case report.
As the COVID-19 pandemic spread worldwide, case reports and small series identified its association with an increasing number of medical conditions including a propensity for thrombotic complications. And since the nephrotic syndrome is also a thrombophilic state, its co-occurrence with the SARS-CoV-2 infection is likely to be associated with an even higher risk of thrombosis, particularly in the presence of known or unknown additional risk factors. Lower extremity deep vein thrombosis (DVT) and pulmonary embolism (PE) are the most common manifestations of COVID-19-associated hypercoagulable state with other venous or arterial sites being much less frequently involved. Although splanchnic vein thrombosis (SVT) has been reported to be 25 times less common than usual site venous thromboembolism (VTE) and rarely occurs in nephrotic patients, it can have catastrophic consequences. A small number of SVT cases have been reported in COVID-19 infected patients in spite of their number exceeding 180 million worldwide. An unvaccinated young adult male with steroid-dependent nephrotic syndrome (SDNS) who was in a complete nephrotic remission relapsed following contracting SARS-CoV-2 infection and developed abdominal pain and diarrhea. Abdominal US revealed portal vein thrombosis. The patient was anticoagulated, yet the SVT rapidly propagated to involve the spleno-mesenteric, intrahepatic and the right hepatic veins. In spite of mechanical thrombectomy, thrombolytics and anticoagulation, he developed mesenteric ischemia which progressed to gangrene leading to bowel resection and a complicated hospital course. Our case highlights the potential for a catastrophic outcome when COVID-19 infection occurs in those with a concomitant hypercoagulable state and reminds us of the need for a careful assessment of abdominal symptoms in SARS-CoV-2 infected patients.


Global achievement of maternal health-related sustainable development goals targets among women exposed to intimate partner violence.
Health-related Sustainable Development Goal (SDG 3) aims to ensure healthy lives. This study investigates the influence of Intimate Partner Violence (IPV) on achieving maternal health related SDG3 targets among exposed women globally. This study used secondary data analysis of Domestic Violence Modules from the latest Demographic and Health Surveys (DHS) of 40 countries. IPV was defined by women ever exposed to emotional, physical, severe, or sexual violence from the spouse. Achieving maternal health related SDG3 targets among women was measured by: Proportion of births attended by skilled health personnel; Antenatal care (women received antenatal care eight or more times from any provider); and the need for family planning satisfied with modern methods. The influence of IPV was estimated through adjusted OR after controlling for socioeconomic factors using logistic regression. Exposure to IPV was among one-third of the women (37%) mainly physical (29%) and emotional (24%). Adjusted OR with 95%CI for the influence of IPV on women's utilization of skilled birth attendants was 0.81 (0.79-0.83)); having eight or more antenatal care visits 0.61 (0.59-0.63); and the needs for family planning with modern methods satisfied was 0.85 (0.83-0.87). Achievement of maternal health services was among 57% of the women. Women exposed to IPV were less to achieve maternal health services (50% VS 61%) with adjusted OR 0.71; 95%CI: 0.70-0.73 and it was not confounded by the positive effect of socioeconomic factors. Exposure to IPV had a statistically significant negative influence on all the maternal health related SDG3 services among women. Programs working in facilitating the achievement of the SDGs related maternal health targets should include prevention of women's exposure to IPV and support for those who are exposed to it.


[Neuronal reactions of the lateral area of the hypothalamus in the rat to stimulation of taste and viscerochemoreceptors].
Unit activity from the rat lateral hypothalamic area was studied in stimulation of tongue taste receptors and chemoreceptors of intestine with salt and acid solutions. 80% of neurons were found to exhibit regular changes in rate of discharges evoked chemical stimulation of either one ("taste", "viscerochemical") or both receptive areas ("convergence" type). When different concentrations of NaCl were applied for stimulation of visceroreceptors, the most pronounced response occurred in minimal (0.05 M) and maximal (0.3 M) concentrations of NaCl used. Some units selectively responded to only one solution. Neurons responding to more than one solution could increase their rate of discharges in one solution and decrease it in another. In "convergence" neurons these distinctions were revealed during application of the same solutions to different receptive zones.


Evaluation of efficacy and safety of traditional Chinese medicine in the treatment of hip synovitis in children: A protocol for systematic review and meta-analysis.
Hip synovitis is a common hip disorder in children and a frequent cause of hip or groin pain in children. Its onset is rapid and poses a threat to patient health. Conventional treatment methods have suboptimal efficacy and large side effects. Clinical study surface, the therapeutic effect of traditional Chinese medicine (TCM) on hip synovitis in children is obvious. Therefore, we aimed to systematically review the efficacy and safety of TCM on hip synovitis in children. We will search databases including PubMed, Web of Science, EMBASE database, Cochrane Library, MEDLINE, Wanfang Data, Chinese biomedical literature database, China National Knowledge Infrastructure, Chinese science and technology journals database, and World Health Organization International Clinical Trials Registry Platform (since the databases were established). We also searched secondary resources, including the reference lists of studies. Included articles were carefully screened and reviewed by 2 researchers. Statistical analysis was performed using Review Manager 5.3 software. This study will comprehensively evaluate the efficacy and safety of TCM for the treatment of hip synovitis in children. This systematic review explores the efficacy and safety of TCM for the treatment of hip synovitis in children and provides an update on its clinical use.


Comparison of panoramic and standard radiographic radiation exposures in the diagnosis of mandibular fractures.
Radiological examination of the maxillofacial region is required to confirm fractures and to identify lesions that are present in the jaws. The complex anatomy of the area necessitates multiple radiographic views with standard projections. The accuracy of diagnosis is at times suspect. An orthopantomogram, which is supplemented by a posteroanterior projection of the lower jaw where required, allows a more accurate diagnosis. This pilot study was designed to compare the radiation dosage that is delivered after a standard hospital series of films and an orthopantomogram. The results demonstrate the significant reduction in irradiation to patients who undergo orthopantomography.


Comparison of the thermoregulatory responses to intracerebroventricularly injected dopamine, noradrenaline and 5-hydroxytryptamine in the goat.
The thermoregulatory responses to dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT), injected into the third cerebral ventricle of goats at 20 degrees C ambient temperature (Ta) or during cold exposure, were compared before and after pretreatment with the DA receptor blocker haloperidol or the 5-HT receptor blocker methysergide. At 20 degrees C Ta, intracerebroventricular (i.c.v.) injection of DA (800 microgram), NA (200 microgram) or 5-HT (800 microgram) induced a decrease in body temperature (Tb) and dilatation of the ear vessels. After DA and 5-HT, but not after NA, panting was observed. During cold exposure both DA and NA caused a suppression of shivering and a fall in Tb. Pretreatment with haloperidol (400 microgram, i.c.v.) attenuated the thermoregulatory effects of i.c.v. DA other than the dilatation of the ear vessels at 20 degrees C Ta. Haloperidol did not influence the responses after i.c.v. NA or 5-HT. Methysergide (1.0 mg, i.c.v.) blocked panting and attenuated the decrease in Tb caused by i.c.v. DA and 5-HT at 20 degrees C Ta and blocked the peripheral vasodilatation caused by 5-HT but not the dilatation caused by DA. During cold exposure methysergide antagonized the thermoregulatory effects of DA, but not those of NA. Ic.v. injection of haloperidol (400 microgram) or methysergide (1.0 mg) during heat exposure induced in panting and a rise in body temperature, which suggests that both DA and 5-HT have a physiological role in the mediation of heat loss in the goat. We conclude that in the central thermoregulatory system of the goat are excitatory DA receptors in the pathway from heat sensors to heat effectors. Activation of these receptors by i.c.v. DA or by heat exposure results in a secondaary release of 5-HT. Since the vasodilating effect of DA was not influenced by haloperidol or methysergide, this effect could be mediated by haloperidol-insensitive (possibly inhibitory) DA receptors on the pathway controlling peripheral vasomotor tone. The thermoregulatory effects of i.c.v. NA are probably mediated by inhibitory NA receptors on the pathway from cold sensors to heat production effectors.


Two types of psychological hedonism.
I develop a distinction between two types of psychological hedonism. Inferential hedonism (or "I-hedonism") holds that each person only has ultimate desires regarding his or her own hedonic states (pleasure and pain). Reinforcement hedonism (or "R-hedonism") holds that each person's ultimate desires, whatever their contents are, are differentially reinforced in that person's cognitive system only by virtue of their association with hedonic states. I'll argue that accepting R-hedonism and rejecting I-hedonism provides a conciliatory position on the traditional altruism debate, and that it coheres well with the neuroscientist Anthony Dickinson's theory about the evolutionary function of hedonic states, the "hedonic interface theory." Finally, I'll defend R-hedonism from potential objections.


The impact of central line bundles on the timing of catheter-associated bloodstream infections and their microbiological distribution in critically ill children.
Catheter-associated bloodstream infection, also known as CLABSI, is the most serious consequence of central venous access devices. These infections increase the risk of mortality and morbidity. The use of central line bundles in clinical settings is increasing worldwide with the purpose of lowering the risk of catheter-associated bloodstream infections. In this study, we investigated the effect of implementing a central line bundle for the prevention of CLABSIs, the distribution of pathogens, and the duration of time it took for CLABSIs to develop in patients who had subclavian-inserted central venous catheters. This research project was a cross-sectional study investigation carried out in a pediatric tertiary teaching hospital. Participants consisted of children who had been admitted to the pediatric critical care unit with subclavian catheters during a period of 13 years. We compared the prebundle period with the bundle period for CLABSI specifically focusing on the time to infection, the number of polymicrobial infections, the proportion of Candida parapsilosis, and the percentage of Coagulase-negative staphylococci (CoNS). The "prebundle period" included the period from May 2007 to May 2013, and the "bundle period" included the period from June 2013 to June 2020. Throughout the course of the study, a total of 286 cases of CLABSI were documented. Among these patients, 141 (49.3%) had CLABSIs associated with subclavian catheters. During the prebundle period, 55 CLABSIs were diagnosed in 5235 central line days, with an overall rate of 10.5 CLABSIs per 1000 central line days; after the implementation of central line bundle, 86 CLABSIs were diagnosed in 12,450 CL days, with an overall rate of 3.6 CLABSIs per 1000 CL days. This showed a statistically significantly lower rate in the bundle period (p = 0.0126). In the prebundle period, the mean time to develop CLABSI was 15 days, whereas during the bundle period, the mean time to develop CLABSI was 27.9 days, a significantly longer time to onset (p = 0.001). While the percentage of other microorganisms was not statistically different between the prebundle and bundle periods (p > 0.05), the percentage of C. parapsilosis was significantly higher in the prebundle period (p = 0.001). Conclusion: The results of this study imply that the use of central line bundles not only reduces the incidence of CLABSI but also delays the time to which CLABSI patients acquire an infection. In addition, as a direct consequence of the CLB, the number of CLABSIs caused by gram-positive cocci did not increase, while the proportion of CLABSIs caused by C. parapsilosis decreased. What is Known: • The most significant negative consequence of central venous access devices is catheter-associated bloodstream infections. • "Care bundles" for CLABSI prevention have been reported to reduce the CLABSI rate. What is New: • Consider what would happen if the "Care bundle" failed to prevent CLABSI. • The findings of this study imply that using central line bundles not only reduces the risk of CLABSI but also extends the time it takes for patients to develop CLABSI. While the number of CLABSIs caused by gram-positive cocci did not increase as a direct result of CLB, the rate of CLABSIs caused by C. parapsilosis, which has recently become a major problem, has decreased.


The effect of citrate loading on exercise performance, acid-base balance and metabolism.
Nine subjects (VO2max 65 +/- 2 ml.kg-1.min-1, mean +/- SEM) were studied on two occasions following ingestion of 500 ml solution containing either sodium citrate (C, 0.300 g.kg-1 body mass) or a sodium chloride placebo (P, 0.045 g.kg-1 body mass). Exercise began 60 min later and consisted of cycle ergometer exercise performed continuously for 20 min each at power outputs corresponding to 33% and 66% VO2max, followed by exercise to exhaustion at 95% VO2max. Pre-exercise arterialized-venous [H+] was lower in C (36.2 +/- 0.5 nmol.l-1; pH 7.44) than P (39.4 +/- 0.4 nmol.l-1; pH 7.40); the plasma [H+] remained lower and [HCO3-] remained higher in C than P throughout exercise and recovery. Exercise time to exhaustion at 95% VO2max was similar in C (310 +/- 69 s) and P (313 +/- 74 s). Cardiorespiratory variables (ventilation, VO2, VCO2, heart rate) measured during exercise were similar in the two conditions. The plasma [citrate] was higher in C at rest (C, 195 +/- 19 mumol.l-1; P, 81 +/- 7 mumol.l-1) and throughout exercise and recovery. The plasma [lactate] and [free fatty acid] were not affected by citrate loading but the plasma [glycerol] was lower during exercise in C than P. In conclusion, sodium citrate ingestion had an alkalinizing effect in the plasma but did not improve endurance time during exercise at 95% VO2max. Furthermore, citrate loading may have prevented the stimulation of lipolysis normally observed with exercise and prevented the stimulation of glycolysis in muscle normally observed in bicarbonate-induced alkalosis.


A cross-sectional study of prevalence and risk factors for childhood asthma in Ahvaz city, Iran.
Childhood asthma is the main public health problem in world, and dramatically has increased in developed as well as developing countries. To assess prevalence and risk factors for asthma based on ISAAC questionnaire. It was a cross-sectional school population-based study which was carried out on 1803 school children aged 6-7 and 13-14 in Ahvaz city, Khuzestan, south west of Iran, in 2011. The International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire was used as a tool to identify prevalence of asthma. Chi-square (χ(2)) test was then used to identify possible potential risk factors associated with asthma. Logistic regression analysis was then applied to determine the various potential risk factors associated with asthma. Data were entered and analyzed using SPSS (version 17) statistical analysis software. The significant level in this study was considered 0.05. The overall prevalence of asthma among school children was 4.9%, but in males it was 5.5% and in females - 4.3%. Also findings have demonstrated that prevalence of asthma was higher among 13-14 years age group (6.1%) as compared to children aged 6-7 (3.7%). The prevalence of wheeze in the last 12 months, wheeze after exercise and playing was 18.1%, 13.9%, and 8.4% respectively. Prevalence of dry cough at night was reported in 17.6%. Prevalence of asthma was highest in winter (2.6%). Prevalence of asthma in children was higher in males than females and prevalence of allergic symptoms will be increased with high air pollution. Family history of asthma was a strong risk factor for childhood asthma.


Changes in 5-HIAA and 5-HT levels in lumbar CSF following morphine administration to conscious dogs.
Monoamine metabolites in the lumbar cerebrospinal fluid were measured by high-performance liquid chromatography with electrochemical detection (HPLC-ECD) in 6 conscious dogs after administration of morphine. The concentrations of dopamine and its metabolites exhibited only small variations whereas a significant increase in serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA) occurred after a latency of 5 min and culminated after 1 h. The increased release of 5-HT and 5-HIAA and behavioral changes (restlessness, sialorrhea) induced by morphine were prevented by administration of naloxone or nalorphine.


Immunological cross-reactivity against a drug mutated HIV-1 protease epitope after DNA multi-CTL epitope construct immunization.
Epitopes in HIV polymerase were analyzed by peptide binding to human leukocyte antigen (HLA) A0201 molecules, the most frequent HLA class in the Caucasian population. We found that HIV-1 protease peptides representing both the wild type and anticipated drug resistance variants of the sequence bound well to HLA-A0201. We also found that wild type as well as a double mutated variant of the epitope was strongly immunogenic in HLA-A0201 transgenic mice, either as individual peptides or encoded in DNA multi-CTL epitope constructs. Immunological cross-reactivity between different variants of the peptide could be seen, suggesting that it may be possible to induce a broad immune response by immunizing with drug resistance-mutated epitopes. This may be of advantage for HIV-1 infected patients since such a response may cause a better outcome of an anti-retroviral drug therapy.


Fluid Therapy for the Emergent Small Animal Patient: Crystalloids, Colloids, and Albumin Products.
Water is essential for life. Without adequate fluid intake, normal body functioning becomes impaired and ultimately can lead to death. A fluid therapy plan should be considered for any small animal patient that has either inadequate fluid intake, excessive fluid loss, or both. A simplified approach to fluid therapy begins with an understanding of the composition of fluid and its distribution within the body. Next, consideration of electrolyte loss, acid-base disturbances, perfusion impairment, and loss of protein also becomes important when replenishing deficits by using various fluids that are commercially available to small animal practitioners.


Availability and scope of integrated screening for patients with Lynch syndrome.
To assess the availability and capacity of US-based integrated centers for the management of Lynch syndrome. A cross-sectional survey of practice patterns in the care of patients with Lynch syndrome was conducted at 33 National Cancer Institute-designated cancer centers in the USA from March 1 to June 1, 2013. Each cancer center was contacted by telephone and the caller used a uniform scripted greeting and survey format. All centers routinely recommended colonoscopy. Other recommended screening modalities were hysterectomy and bilateral salpingo-oophorectomy (29/33; 88%), endoscopy (27/33; 82%), urinalysis (23/33; 70%), endometrial sampling (21/33; 64%), dermatologic examination (19/32; 59%), pelvic ultrasonography (18/33; 55%), serum CA125 level (14/33; 42%), urine cytology (14/33; 42%), computed tomography (1/33; 3%), and magnetic resonance imaging (1/33; 3%). Each center had a multidisciplinary team but the composition varied. A designated team leader was present at 21 centers (64%). Having a team leader was associated with an increased likelihood of recommending endoscopy (P=0.04) and dermatologic surveillance (P=0.01). Only 23 centers (70%) had a system in place for communicating follow-up with patients. The lack of consensus in practice patterns recorded among participating centers probably reflected the limited existing evidence on the usefulness of most screening modalities.


Cut5 is a component of the UV-responsive DNA damage checkpoint in fission yeast.
A checkpoint responding to DNA damage in G2 results in a delay in the onset of mitosis through inhibition of p34cdc2 kinase activity via maintenance of inhibitory tyrosine phosphorylation. Genetic analyses of this checkpoint in fission yeast have identified single alleles of several genes, suggesting these screens are not yet saturating, and hence further genes await identification. To fully understand the complexity of this checkpoint it will be necessary to define all the genes involved. To this end we screened for new mutants defective in the ability to delay mitosis in the presence of DNA-damaging agents. Twenty-four mutants were isolated that were defective in UV-C and MMS-induced checkpoint delay. Amongst these mutants was an allele of cut5 that was also defective in the checkpoint responses. We show here, contrary to previous reports, that the UV-C induced checkpoint response is defective in cut5 mutants. Therefore, like all other checkpoint mutants, cut5 is required for G2 checkpoint arrest following DNA damage, regardless of the nature of the lesions involved.


Exploring and engineering PAM-diverse Streptococci Cas9 for PAM-directed bifunctional and titratable gene control in bacteria.
The RNA-guided Cas9s serve as powerful tools for programmable gene editing and regulation; their targeting scopes and efficacies, however, are always constrained by the PAM sequence stringency. Most Streptococci Cas9s, including the prototype SpCas9 from S. pyogenes, specifically recognize a canonical NGG PAM via a conserved RxR PAM-binding motif within the PAM-interaction (PI) domain. Here, SpCas9-based mining unveils three distinct and rarely presented PAM-binding motifs (QxxxR, QxQ and RxQ) among Streptococci Cas9 orthologs. With the catalytically-dead QxxxR-containing SedCas9 from S. equinus, we dissect its NAG PAM specificity and elucidate its underlying recognition mechanism via computational prediction and mutagenesis analysis. Replacing the SedCas9 PI domain with alternate PAM-binding motifs rewires its PAM specificity to NGG or NAA. Moreover, a semi-rational design with minimal mutation creates a SedCas9-NQ variant showing robust activity towards expanded NNG and NAA PAMs, based upon which we engineered a compact ω-SedCas9-NQ transcriptional regulator for PAM-directed bifunctional and titratable gene control. The ω-SedCas9-NQ mediated metabolic reprogramming of endogenous genes in Escherichia coli affords a 2.6-fold increase of 4-hydroxycoumarin production. This work reveals new Cas9 scaffolds with distinct PAM-binding motifs for PAM relaxation and creates a new PAM-diverse Cas9 variant for versatile gene control in bacteria.


Recording pattern reversal visual evoked response with the scanning laser ophthalmoscope.
We recorded visual evoked responses (VERs) to alternating, checkerboard pattern stimuli using the scanning laser ophthalmoscope (SLO). Retinal position and focus of checkerboard stimuli were monitored on the SLO video monitor throughout testing. Checkerboard size, check size, and retinal positions were varied. Consistent with other, well-established pattern reversal techniques, the SLO method produced: 1) reliable VERs with amplitudes of 2 to 10 microvolts, 2) maximum amplitudes at an intermediate check size for a fixed overall pattern size, and 3) variations in VER amplitude depending on stimulus retinal position relative to the fovea. Hence, the SLO-VER technique would be useful for clinical VER measurements when precise retinal stimulus position and focus are desired.


Differential expression of melanoma-associated growth factors in keratinocytes and fibroblasts by ultraviolet A and ultraviolet B radiation.
Besides the direct DNA-damaging effects of ultraviolet (UV) radiation on cells, indirect effects on the microenvironment of the skin may facilitate melanoma development. A stimulation of growth factor production by cells in the immediate environment of melanocytes may lead to a paracrine activation and proliferation of melanocytes that in turn become more susceptible to transformation. We investigated whether the expression of growth factors for melanocytes can be modulated in keratinocytes and fibroblasts by UVA or UVB. After irradiation with different doses of UVA or UVB, protein expression of basic fibroblast growth factor (bFGF), endothelin (ET)-1, transforming growth factor (TGF)-beta1, platelet-derived growth factor (PDGF)-AA, stem cell factor (SCF) and hepatocyte growth factor (HGF) was analysed by quantitative enzyme-linked immunosorbent assay. The mRNA expression of bFGF and ET-1 was analysed by quantitative real-time reverse transcriptase-polymerase chain reaction. In keratinocytes, UVB and UVA increased bFGF protein levels up to 2.6-fold. This increase was paralleled by elevated mRNA levels. UVB also induced ET-1 protein up to 1.8-fold, while UVA led to an 80% decrease. Secreted TGF-beta1 and PDGF-AA were downregulated by UVA by less than 50%, while there was no significant alteration by UVB. Secreted SCF was not changed significantly by UVA or UVB. In fibroblasts, bFGF protein levels were increased 11-64-fold by UVA and 34-61-fold by UVB. This was paralleled by elevated mRNA levels for bFGF up to 2.7-fold. HGF protein was stimulated by UVA up to 2.8-fold and by UVB up to 6.7-fold, while TGF-beta1 protein was increased up to 2.7-fold by UVB and 1.7-fold by UVA. UVA and UVB can stimulate and inhibit the production of growth factors for melanocytes in keratinocytes and fibroblasts dependent on the cell type and wavelength. We show for the first time that UVA and UVB can activate bFGF, HGF and TGF-beta1 in fibroblasts, while bFGF was the most inducible factor both in fibroblasts and in keratinocytes. The induction of bFGF and HGF in fibroblasts by UVA suggests that stroma cells in the dermis may be involved in the UV activation of melanocytes via paracrine ways and thus promote melanoma development.


Defective cell death signalling along the Bcl-2 regulated apoptosis pathway compromises Treg cell development and limits their functionality in mice.
The Bcl-2 regulated apoptosis pathway is critical for the elimination of autoreactive lymphocytes, thereby precluding autoimmunity. T cells escaping this process can be kept in check by regulatory T (Treg) cells expressing the transcription and lineage commitment factor Foxp3. Despite the well-established role of Bcl-2 family proteins in shaping the immune system and their frequent deregulation in autoimmune pathologies, it is poorly understood how these proteins affect Treg cell development and function. Here we compared the relative expression of a panel of 40 apoptosis-associated genes in Treg vs. conventional CD4(+) T cells. Physiological significance of key-changes was validated using gene-modified mice lacking or overexpressing pro- or anti-apoptotic Bcl-2 family members. We define a key role for the Bim/Bcl-2 axis in Treg cell development, homeostasis and function but exclude a role for apoptosis induction in responder T cells as relevant suppression mechanism. Notably, only lack of the pro-apoptotic BH3-only protein Bim or Bcl-2 overexpression led to accumulation of Treg cells while loss of pro-apoptotic Bad, Bmf, Puma or Noxa had no effect. Remarkably, apoptosis resistant Treg cells showed reduced suppressive capacity in a model of T cell-driven colitis, posing a caveat for the use of such long-lived cells in possible therapeutic settings.


Exploring the structure-activity relationships of ABCC2 modulators using a screening approach.
ABCC2 is a transporter with key influence on liver and kidney pharmacokinetics. In order to explore the structure-activity relationships of compounds that modulate ABCC2, and by doing so gain insights into drug-drug interactions, we screened a library of 432 compounds for modulators of radiolabeled β-estradiol 17-(β-d-glucuronide) (EG) and fluorescent 5(6)-carboxy-2',7'-dichlorofluorescein transport (CDCF) in membrane vesicles. Following the primary screen at 80μM, dose-response curves were used to investigate in detail 86 compounds, identifying 16 low μM inhibitors and providing data about the structure-activity relationships in four series containing 19, 24, 10, and eight analogues. Measurements with the CDCF probe were consistently more robust than for the EG probe. Only one compound was clearly probe-selective with a 50-fold difference in the IC50s obtained by the two assays. We built 24 classification models using the SVM and fused-XY Kohonen methods, revealing molecular descriptors related to number of rings, solubility and lipophilicity as important to distinguish inhibitors from inactive compounds. This study is to the best of our knowledge the first to provide details about structure-activity relationships in ABCC2 modulation.


Differential mRNA expression profiling in ovarian endometriotic tissue with versus without leuprolide acetate treatment.
Leuprolide acetate, an analog of gonadotropin-releasing hormone (GnRH), regresses endometriotic tissue and reduces pain, resulting in clinical improvement upon treatment. The molecular mechanisms involved in the regression of endometriotic tissue, however, remain to be elucidated. In this study, we performed genome-wide gene expression profiling of clinical specimens of ovarian endometrioma to obtain insight into the effects of leuprolide acetate treatment. We obtained clinical samples from nine normal eutopic endometrium tissues, eight ovarian endometriotic tissues, and 12 leuprolide acetate-treated endometriotic tissues. We compared the gene expression profiles of the three groups using Affymetrix GeneChip Human genome arrays and bioinformatic analysis, including molecular concept analysis. Leuprolide acetate-treated endometriotic tissue showed downregulated genes associated with the biological functions of steroid hormone regulation, cell proliferation, inflammation, and intracellular signaling. These genes included PTGDS, GRP, APLP2, PLTP, and FGFRL1. In contrast, genes upregulated by leuprolide acetate treatment were associated with cell growth inhibition and apoptosis. These genes included CARD11 and USP18. These preliminary results based on GeneChip analysis suggest that leuprolide acetate treatment induces a modulation of gene expression that allows for cooperative alterations in disease state. This study gives new insight into the effects of leuprolide acetate treatment. Further investigations with quantitative reverse transcription-polymerase chain reaction and immunohistochemistry are needed to validate this study and to explore new therapeutic targets and biomarkers of endometriosis.


Interferon gamma treatment for cervical intraepithelial neoplasia.
Eight patients with cervical intraepithelial neoplasia (CIN) were administered perilesional injections of human recombinant interferon gamma (IFN-gamma), and the response was evaluated by colposcopy and exfoliative cytology and then by histopathology. In all patients, colposcopic and cytologic findings improved after two to four injections of IFN-gamma and the cytologic findings reverted to normal in five of these eight patients. All five were free of dysplastic lesions. The other three patients with positive cytology and positive colposcopy after completion of IFN-gamma treatment underwent hysterectomy or laser conization, and histopathologic examination revealed residual dysplastic lesions. On the other hand, a control study revealed that only one of eight patients showed spontaneous regression during the 3-month observation period. During the course of these treatments, keratinizing cells were often present in the cervical smears and isolated cell keratinization was often evident in the residual dysplastic lesions of the surgical specimens. These observations suggest that IFN-gamma treatment is an effective therapeutic method for CIN lesions and that IFN-gamma has the potential to differentiate nonkeratinizing squamous cells into keratinizing cells.


Analysis of melting reconstruction treatment and cement solidification on ultra-risk municipal solid waste incinerator fly ash-blast furnace slag mixtures.
High temperature melting treatment and cement solidification are technologies currently used to reduce the leaching of heavy metals in municipal solid waste incinerator (MSWI) fly ash. In this paper, to ascertain the feasibility of melting MSWI fly ash with blast furnace (BF) slag, ultra-risk MSWI(U-MSWI) fly ash having high heavy metal (Zn, Pb, Cu, and Cr) contents were blended with BF slag, then melted and quenched into water to prepare reconstructed slag. The melting and solidification behaviors, phase composition and microstructure, and heavy metal leachability of reconstructed slag were studied. In addition, to study the further solidification and utilization of reconstructed slag in cement, the compressive strength and leaching concentration of cement composites with reconstructed slag were also investigated. The results indicate that the presence of heavy metals in the U-MSWI fly ash had a little influence on the microstructure and phase composition of reconstructed slag. The leaching concentration of heavy metals in the reconstructed slag increased with the increasing of U-MSWI fly ash content, and when the content of U-MSWI fly ash was less than 50 wt%, the reconstructed slag could meet the environmental requirements. The reconstructed slag further solidified by cement could be applied to landfill and construction materials. The technology of melting reconstruction treatment with cement solidification was a technical-economical choice for the industrial treatment of U-MSWI fly ash.


Enzymatic patterns in reptilian brain. Histochemical characterization of the optic tectum.
The enzymatic patterns present in the optic tectum of 4 species belonging to different reptilian orders seem related to the degree of structural and functional organization reached by the nervous centre, as in other vertebrates. In particular the AChE localization in reptiles is representative of a evolutionary sequence in the distribution of this enzyme in the optic tectum along the tetrapode series.


Distal pressure monitoring and titration with percent balloon volume: feasible management of partial resuscitative endovascular balloon occlusion of the aorta (P-REBOA).
Resuscitative endovascular balloon occlusion of the aorta (REBOA) increases proximal arterial pressure, but may also induce life-threatening distal ischemia. Partial REBOA (P-REBOA) is thought to mitigate distal ischemia during aortic occlusion. However, feasible indicators of the degree of P-REBOA remain inconsistent. We hypothesised percent balloon volume could be a substitute for pressure measurements of gradients during P- REBOA. This study aimed to compare balloon volume and arterial pressure gradient, and analysed with intra-balloon pressure and balloon shape. Proximal (carotid) and distal (femoral) arterial pressures were recorded and a 7-Fr REBOA catheter was placed in four swine. Total REBOA was defined as a cessation of distal pulse pressure and maximum balloon volume was documented. The balloon volume was titrated by 20% increments of maximum capacity to adjust the degree of P-REBOA. The distal/proximal arterial pressure gradient and the intra-balloon pressures were also recorded. The changes in shape and the cross-sectional area of the balloon were evaluated with computed tomography (CT) images. The proximal mean arterial pressure (MAP) plateaued after 60% balloon volume; meanwhile, distal pulse pressure was still left. The balloon pressure was traced with proximal MAP before contact with aortic wall. The balloon shape changed unevenly from "cone" to "spindle" shape, although the balloon cross-sectional area of the mid-segment linearly increased. Monitoring distal pressure and titrating percent balloon volume is feasible to manage P-REBOA. In this experiment, 60% balloon volume was enough inflation to elevate central pressure allowing distal perfusion. The intra-balloon pressure was not reliable due to the strong influence of proximal MAP and uneven change of the balloon shape.


Augmented feedback of COM and COP modulates the regulation of quiet human standing relative to the stability boundary.
The experiment manipulated real-time kinematic feedback of the motion of the whole body center of mass (COM) and center of pressure (COP) in anterior-posterior (AP) and medial-lateral (ML) directions to investigate the variables actively controlled in quiet standing of young adults. The feedback reflected the current 2D postural positions within the 2D functional stability boundary that was scaled to 75%, 30% and 12% of its original size. The findings showed that the distance of both COP and COM to the respective stability boundary was greater during the feedback trials compared to a no feedback condition. However, the temporal safety margin of the COP, that is, the virtual time-to-contact (VTC), was higher without feedback. The coupling relation of COP-COM showed stable in-phase synchronization over all of the feedback conditions for frequencies below 1Hz. For higher frequencies (up to 5Hz), there was progressive reduction of COP-COM synchronization and local adaptation under the presence of augmented feedback. The findings show that the augmented feedback of COM and COP motion differentially and adaptively influences spatial and temporal properties of postural motion relative to the stability boundary while preserving the organization of the COM-COP coupling in postural control.


CONS-COCOMAPS: a novel tool to measure and visualize the conservation of inter-residue contacts in multiple docking solutions.
The development of accurate protein-protein docking programs is making this kind of simulations an effective tool to predict the 3D structure and the surface of interaction between the molecular partners in macromolecular complexes. However, correctly scoring multiple docking solutions is still an open problem. As a consequence, the accurate and tedious screening of many docking models is usually required in the analysis step. All the programs under CONS-COCOMAPS have been written in python, taking advantage of python libraries such as SciPy and Matplotlib. CONS-COCOMAPS is freely available as a web tool at the URL:http://www.molnac.unisa.it/BioTools/conscocomaps/. Here we presented CONS-COCOMAPS, a novel tool to easily measure and visualize the consensus in multiple docking solutions. CONS-COCOMAPS uses the conservation of inter-residue contacts as an estimate of the similarity between different docking solutions. To visualize the conservation, CONS-COCOMAPS uses intermolecular contact maps. The application of CONS-COCOMAPS to test-cases taken from recent CAPRI rounds has shown that it is very efficient in highlighting even a very weak consensus that often is biologically meaningful.


Multifidus innervation and muscle assessment post-spinal surgery.
Assessment of the integrity of the multifidus muscles and corresponding nerve roots, post-open (OSS) versus minimally invasive spinal surgery (MISS) for lumbar spine fractures. We investigated the first six patients undergoing MISS in our institution and age- and sex-matched them with 6 random patients who previously had OSS. All had a similar lumbar fracture configuration without evidence of spinal cord injury. All were assessed using ultrasound muscle quantification and electromyographic studies at a minimum of 6 months post-operatively. Mean cross-sectional area (CSA) was measured at sequential levels within and adjacent to the operative field. Concentric needle electromyography was performed at instrumented and adjacent non-instrumented levels in each patient. Mean CSA across all lumbar multifidus muscles was 4.29 cm(2) in the MISS group, 2.26 cm(2) for OSS (p = 0.08). At the instrumented levels, mean CSA was 4.21 cm(2) for MISS and 2.03 cm(2) for OSS (p = 0.12). At non-instrumented adjacent levels, mean CSA was 4.46 cm(2) in the MISS group, 2.87 cm(2) for OSS (p = 0.05). Electromyography at non-instrumented adjacent levels demonstrated nerve function within normal limits in 5/6 levels in the MISS group compared to 1/6 levels in the OSS (p = 0.03). Instrumented levels demonstrated nerve function within normal limits in 5/12 levels in the MISS group compared with 4/12 in the OSS group, including moderate-severe denervation at 5 levels in the OSS group (p = 0.15). Posterior instrumented MISS demonstrates a significantly superior preservation of the medial branch of the posterior ramus of the spinal nerve and less muscle atrophy, particularly at adjacent levels when compared to OSS.


Residents' perceptions of household food waste during the COVID-19 outbreak in Korea.
Analyzing household food waste data at the global or national level remains a challenge, especially owing to lack of statistical systems and socio-cultural differences. This study determined the factors affecting the intention of households to reduce food waste on Jeju Island and on the Korean mainland. Socio-demographic factors significantly influence household food waste generation. Therefore, studies are often conducted depending on data availability in the corresponding regions. Based on national data and the theory of planned behavior, this study analyzed data using PLS-SEM (Partial Least Squares Structural Equation Modeling) to test the influence of multiple determinants and parameters on dependent variables and investigated the awareness of household food waste in Korea, focusing on Jeju Province, Korea's largest tourist destination. A survey of 508 local residents established that all factors evaluated in this study, except for risk concerns due to COVID-19, were statistically significant. Among the three antecedents of age, income, and family size, age significantly affected all mediators, directly affecting behavioral intentions. The results are consistent with those of preceding research on the effects of socio-demographic drivers on household food waste generation. The results also indicate that in Korea, where the COVID-19 infection level is lower than that in other countries, residents did not change their food purchasing and waste production patterns. However, a multi-group analysis revealed that the risk concerns caused by COVID-19 differed between residents of Jeju Island and mainland Korea. Overcoming the vulnerability of waste management, including food dumping, is mandatory for locals and tourists on Jeju Island.