Nutrition for diabetic retinopathy: plummeting the inevitable threat of diabetic vision loss.
Diabetic retinopathy (DR) is among the leading causes of preventable blindness. Hyperglycemia, hypertension, hyperlipidemia and anemia majorly predispose its pathogenesis. The current treatment modalities of DR include laser photocoagulation therapy, intravitreal corticosteroids, intravitreal anti-vascular endothelial growth factor (VEGF) agents and vitreo-retinal surgery which are costly, highly invasive, unproven for prolonged use and opted in advanced stages of DR. By then retina already encounters a vast damage. Nutrients by their natural physiological, biochemical and molecular action can preserve retinal structure and functions by interfering with the various pathological steps prompting DR incidence, thereby altering the risk of developing this ocular morbidity. Nutrients can also play a central role in DR patients resistant towards the conventional medical treatments. However due to the byzantine interplay existing between nutrients and DR, the worth of nutrition in curbing this vision-threatening ocular morbidity remains silent. This review highlights how nutrients can halt DR development. A nutritional therapy, if adopted in the initial stages, can provide superior-efficacy over the current treatment modalities and can be a complementary, inexpensive, readily available, anodyne option to the clinically unmet requirement for preventing DR. Assessment of nutritional status is presently considered relevant in various clinical conditions except DR. Body Mass Index (BMI) conferred inconclusive results in DR subjects. Subjective Global Assessment (SGA) of nutritional status has recently furnished relevant association with DR status. By integrating nutritional strategies, the risk of developing DR can be reduced substantially. This review summarizes the subsisting knowledge on nutrition, potentially beneficial for preventing DR and sustaining good vision among diabetic subjects.


Minerals of the Radular Apparatus of Falcidens sp. (Caudofoveata) and the Evolutionary Implications for the Phylum Mollusca.
Minerals have been found in the radular teeth of molluscs from the classes Caudofoveata, Polyplacophora, Monoplacophora, and Gastropoda (Patellogastropoda: Acmaeidae, Patellidae). Here we report the discovery of amorphous iron oxide and hydroxyapatite in the highly modified radular apparatus of Falcidens sp. (Caudofoveata). The mineralization process in Falcidens sp. is unique: the components of the radular apparatus, unlike those of other molluscs, are not renewed during the animal's lifetime. We propose that the presence of mineralized teeth among the molluscs is not necessarily connected to their manner of obtaining food and suggest that the molluscan common ancestor had mineralized teeth.


Influence of post-LASIK corneal healing on scanning laser polarimetric measurement of the retinal nerve fibre layer thickness.
To investigate the influence of laser assisted in situ keratomileusis (LASIK) on the values for retinal nerve fibre layer thickness (RNFLT) as measured with scanning laser polarimetry (SLP) during the healing process of the cornea after LASIK. SLP with the GDx instrument was performed on 20 consecutive healthy subjects without any eye disease undergoing LASIK for ametropia correction. The SLP measurements were performed before the surgery, and at 1 and 3 days, as well as at 3 months, after LASIK. Thickness data from images of one randomly selected eye per subject were analysed using the ANOVA and Duncan multiple comparison tests. Correlation coefficients between RNFLT data and the treatment parameters were also calculated. Somewhat similar results were found for the different retinal areas. The measured values for superior average RNFLT decreased significantly at all time points compared to the preoperative baseline (p<0.003, Duncan test), but increased significantly between postoperative day 1 and the final visit at 3 months (p=0.025, Duncan test). Inferior average RNFLT in the early postoperative days was significantly smaller than at 3 months after LASIK (p<0.05, Duncan test), and tended to be smaller than at baseline. The thickness values before surgery and at the final visit, however, showed no significant difference (p=0.698, Duncan test) in this region. Ellipse average RNFLT was significantly smaller in the early postoperative days than the baseline value before LASIK. However, the measured value had significantly increased again by the time of the final visit (p<0.02, Duncan test). This value at the final visit showed no difference from the baseline value (p=0.46, Duncan test). The changes in the nasal average and temporal average RNFLT were not statistically significant. No correlation was found between the change in the SLP measured thickness values and central corneal thickness at baseline and its change after surgery, nor with the change in cylindrical correction due to LASIK, or the length of the suction time during surgery (p>0.05 for all correlations). The SLP technique is sensitive to the corneal optical properties, and RNFLT as measured with SLP shows changes after LASIK. Most of these changes, however, diminish with time after surgery, and the values tend to return to the preoperative results during the first 3 months of corneal healing following uncomplicated LASIK. It appears that in uncomplicated cases the transient RNFLT changes are artefacts and do not imply pathological thickness alterations due to LASIK.


ECHINODERM IMMUNOLOGY: BACTERIAL CLEARANCE BY THE SEA URCHIN STRONGYLOCENTROTUS PURPURATUS.
Characteristics of bacterial clearance were investigated in the purple sea urchin, Strongylocentrotus purpuratus (Echinodermata: Echinoidea). Primary clearance kinetics were determined for three bacteria, a marine Gram negative motile rod, a marine Gram positive non-motile rod, and a Gram negative freshwater fish pathogen, Aeromonas salmonicida. Clearance kinetics differed for each of the three bacteria. Secondary clearance rates were not significantly different from primary clearance rates for any of the three bacteria, regardless of the time interval between inoculations (9-21 days), implying a probable absence of immunologic memory. During primary clearance, total coelomocyte counts declined 93% by 90 min post injection. All four coelomocyte types declined, however the relative proportions of each type changed during the six-hour sampling period. In cell-free coelomic fluid, viable counts of marine bacteria declined, with different kinetics for the two species. Viable counts in sea water controls did not change. Declines in viable counts may be due to bactericidal activity and/or agglutination, although bacterial agglutination was not observed.


Ab initio and DFT predictions of infrared intensities and Raman activities.
Relative infrared (IR) intensities and relative Raman activities have been computed for vibrations of test molecules, including from two to nine heavy atoms, using second-order Moller-Plesset perturbation theory (MP2), and three hybrid density functionals (B3LYP, M05, and M05-2X). The basis set convergence of vibrational properties is discussed. Our results demonstrate that B3LYP offers the most cost-effective choice for the prediction of molecular vibrational properties, but the predictions of another two tested hybrid functionals are very similar and in very good agreement with experimental data. MP2 shows good performance for the IR intensities, whereas the quality of prediction of the relative Raman activities should be characterized as only moderate. B3LYP calculations of the relative IR intensities using highly compact Sadlej's Z3PolX basis set retain the high accuracy of the more CPU expensive Sadlej's pVTZ and much more expensive aug-cc-pVTZ calculations. Relative Raman activities are more sensitive to basis set effects and require at least Sadlej's pVTZ to obtain quantitative results.


Mechanisms involved in the intrinsic isoniazid resistance of Mycobacterium avium.
Isoniazid (INH), which acts by inhibiting mycolic acid biosynthesis, is very potent against the tuberculous mycobacteria. It is about 100-fold less effective against Mycobacterium avium. This difference has often been attributed to a decreased permeability of the cell wall. We measured the rate of conversion of radiolabelled INH to 4-pyridylmethanol by whole cells and cell-free extracts and estimated the permeability barrier imposed by the cell wall to INH influx in Mycobacterium tuberculosis and M. avium. There was no significant difference in the relative permeability to INH between these two species. However, the total conversion rate in M. tuberculosis was found to be four times greater. Examination of in vitro-generated mutants revealed that the major resistance mechanism for both species is loss of the catalase-peroxidase KatG. Analysis of lipid and protein biosynthetic profiles demonstrated that the molecular target of activated INH was identical for both species. M. avium, however, formed colonies at INH concentrations inhibitory for mycolic acid biosynthesis. These mycolate-deficient M. avium exhibited altered colony morphologies, modified cell wall ultrastructure and were 10-fold more sensitive to treatment with hydrophobic antibiotics, such as rifampin. These findings may significantly impact the design of new therapeutic regimens for the treatment of infections with atypical mycobacteria.


Effects of postcesarean section febrile morbidity on subsequent fertility.
The records of 1319 patients undergoing cesarean section were evaluated to determine the relationship between postoperative febrile morbidity and fertility during the five years after the operation. Infection was significantly more common among patients undergoing primary as compared with repeat cesarean section and was three times more frequent among patients with membranes ruptured for 12 hours or more compared with those with membranes ruptured less than 12 hours. After correction of the data for voluntary infertility, neither postcesarean section endometritis nor pelvic cellulitis had a demonstrable effect on the rate of pregnancy during the five years after cesarean delivery, but pelvic abscess was associated with an apparent reduction in fertility as reflected by the frequency of pregnancy among these individuals, which was approximately half the rate observed in other infected and noninfected individuals in this study.


Subharmonics and superharmonics of the weak field in a driven two-level quantum system: Vibrational resonance enhancement.
We consider a quantum two-level system in bichromatic classical time-periodic fields, the frequency of one of which far exceeds that of the other. Based on systematic separation of timescales and averaging over the fast motion a reduced quantum dynamics in the form of a nonlinear forced Mathieu equation is derived to identify the stable oscillatory resonance zones intercepted by unstable zones in the frequency-amplitude plot. We show how this forcing of the dressed two-level system may generate the subharmonics and superharmonics of the weak field in the stable region, which can be amplified by optimization of the strength of the high frequency field. We have carried out detailed numerical simulations of the driven quantum dynamics to corroborate the theoretical analysis.


DAP kinase and DRP-1 mediate membrane blebbing and the formation of autophagic vesicles during programmed cell death.
Death-associated protein kinase (DAPk) and DAPk-related protein kinase (DRP)-1 proteins are Ca+2/calmodulin-regulated Ser/Thr death kinases whose precise roles in programmed cell death are still mostly unknown. In this study, we dissected the subcellular events in which these kinases are involved during cell death. Expression of each of these DAPk subfamily members in their activated forms triggered two major cytoplasmic events: membrane blebbing, characteristic of several types of cell death, and extensive autophagy, which is typical of autophagic (type II) programmed cell death. These two different cellular outcomes were totally independent of caspase activity. It was also found that dominant negative mutants of DAPk or DRP-1 reduced membrane blebbing during the p55/tumor necrosis factor receptor 1-induced type I apoptosis but did not prevent nuclear fragmentation. In addition, expression of the dominant negative mutant of DRP-1 or of DAPk antisense mRNA reduced autophagy induced by antiestrogens, amino acid starvation, or administration of interferon-gamma. Thus, both endogenous DAPk and DRP-1 possess rate-limiting functions in these two distinct cytoplasmic events. Finally, immunogold staining showed that DRP-1 is localized inside the autophagic vesicles, suggesting a direct involvement of this kinase in the process of autophagy.


Protection for Children Born Through Assisted Reproductive Technologies Act, B.E. 2558: The Changing Profile of Surrogacy in Thailand.
The National Legislative Assembly of Thailand has enacted on February 19, 2015 the Protection for Children Born through Assisted Reproductive Technologies Act (ART Act). Its primary objective aims at protecting children born through assisted reproductive technologies and providing the legal procedures that the intended parents must follow. The focus of this article is to discuss the ongoing issues involving assisted reproduction in Thailand. After reviewing the past legal framework surrounding surrogate motherhood and the downsides of the assisted reproductive technology market in Thailand, the article will discuss the new ART Act and its regulatory framework. It will conclude that although the new law contains some flaws and limitations, it has so far been successful in tackling surrogacy trafficking and preventing reproductive scandals from occurring again.


The Preparation, Antioxidant Activity Evaluation, and Iron-Deficient Anemic Improvement of Oat (Avena sativa L.) Peptides-Ferrous Chelate.
Iron-chelating peptides have been widely considered as one of the best iron supplements to alleviate the iron deficiency. In this study, a novel oat peptides-ferrous (OP-Fe2+) chelate was prepared from antioxidant oat peptides obtained in the laboratory of the authors. The optimal preparation condition was obtained through the single-factor and response surface methodology, and the chelating rate could reach up to 62.6%. After chelation, the OP-Fe2+ chelate exhibited a significantly higher 2,2-diphenyl-1-picrylhydrazyl radical scavenging activity than oat peptides. It was discovered that the hemoglobin concentration and the number of red blood cell levels in OP-Fe2+-treated iron-deficient anemic (IDA) rats were significantly higher than untreated IDA rats. The OP-Fe2+ chelate could also improve the hypertrophy of the spleen, serum iron (SI), total iron and binding capacity, and serum ferritin levels in the IDA rats. In addition, the OP-Fe2+ treatment significantly increased the antioxidant activities of super oxidase and glutathione in the liver homogenate of the IDA rats. Therefore, the OP-Fe2+ chelate is an effective type of iron supplement for IDA rats, which could be a promising source with anti-anemia and antioxidant activity.


Assessing Concordance With Watson for Oncology, a Cognitive Computing Decision Support System for Colon Cancer Treatment in Korea.
IBM Watson for Oncology (WFO) is a clinical decision-support computing system that provides oncologists with evidence-based treatment recommendations for a variety of cancer diagnoses. The evidence-based supported treatment recommendations are presented in three categories: Recommended, representing the Memorial Sloan Kettering Cancer Center (MSKCC) preferred approach; For Consideration, evidence-based alternative treatments; and Not Recommended, alternative therapies that may be unacceptable. We examined the absolute concordance of treatment options with that of the recommendations of a multidisciplinary team of oncologists from Gachon University, Gil Medical Centre, Incheon, South Korea. We enrolled 656 patients with stage II, III, and IV colon cancer between 2009 and 2016. Cases were processed using WFO and, using retrospective clinical data, outputs were compared with the actual treatment the patient received. Absolute concordance was defined as an alignment of recommendation in the Recommended MSKCC preferred-approach category. Treatment recommendations that were represented in the For Consideration category were not the focus of this study. The absolute concordance between the WFO-derived MSKCC preferred approach and Gil Medical Centre treatment recommendations was 48.9%. The percentage of cases found to be acceptable was 65.8% (432 of 656) and the stage-specific concordance rate was 32.5% for patients with stage II disease who had risk factors and 58.8% for patients with stage III disease. Patients 70 years of age and older had a concordance rate of only 20.2%, whereas younger patients had a concordance rate of 63.8% ( P = .0001). The main reasons attributed to the low concordance rate were age, reimbursement plan, omitting chemotherapy after liver resection, and not recommending biologic agents (ie, cetuximab and bevacizumab).


The structural basis for specificity in lipoxygenase catalysis.
Many intriguing facets of lipoxygenase (LOX) catalysis are open to a detailed structural analysis. Polyunsaturated fatty acids with two to six double bonds are oxygenated precisely on a particular carbon, typically forming a single chiral fatty acid hydroperoxide product. Molecular oxygen is not bound or liganded during catalysis, yet it is directed precisely to one position and one stereo configuration on the reacting fatty acid. The transformations proceed upon exposure of substrate to enzyme in the presence of O2 (RH + O2 → ROOH), so it has proved challenging to capture the precise mode of substrate binding in the LOX active site. Beginning with crystal structures with bound inhibitors or surrogate substrates, and most recently arachidonic acid bound under anaerobic conditions, a picture is consolidating of catalysis in a U-shaped fatty acid binding channel in which individual LOX enzymes use distinct amino acids to control the head-to-tail orientation of the fatty acid and register of the selected pentadiene opposite the non-heme iron, suitably positioned for the initial stereoselective hydrogen abstraction and subsequent reaction with O2 . Drawing on the crystal structures available currently, this review features the roles of the N-terminal β-barrel (C2-like, or PLAT domain) in substrate acquisition and sensitivity to cellular calcium, and the α-helical catalytic domain in fatty acid binding and reactions with O2 that produce hydroperoxide products with regio and stereospecificity. LOX structures combine to explain how similar enzymes with conserved catalytic machinery differ in product, but not substrate, specificities.


Biochemical characterization of spleen tyrosine kinase (SYK) isoforms in platelets.
Alternate splicing is among the regulatory mechanisms imparting functional diversity in proteins. Studying protein isoforms generated through alternative splicing is therefore critical for understanding protein functions in many biological systems. Spleen tyrosine kinase (Syk) plays an essential role in ITAM/hemITAM signaling in many cell types, including platelets. However, the spectrum of Syk isoforms expressed in platelets has not been characterized. Syk has been shown to have a full-length long isoform SykL and a shorter SykS lacking 23 amino acid residues within its interdomain B. Furthermore, putative isoforms lacking another 23 amino acid-long sequence or a combination of the two deletions have been postulated to exist. In this report, we demonstrate that mouse platelets express full-length SykL and the previously described shorter isoform SykS, but lack other shorter isoforms, whereas human platelets express predominantly SykL. These results both indicate a possible role of alternative Syk splicing in the regulation of receptor signaling in mouse platelets and a difference between signaling regulation in mouse and human platelets.


Inlays made from a hybrid material: adaptation and bond strengths.
The aim of this study was to evaluate the internal fit, marginal adaptation, and bond strengths of inlays made of computer-aided design/computer-aided manufacturing feldspathic ceramic and polymer-infiltrated ceramic. Twenty molars were randomly selected and prepared to receive inlays that were milled from both materials. Before cementation, internal fit was achieved using the replica technique by molding the internal surface with addition silicone and measuring the cement thicknesses of the pulpal and axial walls. Marginal adaptation was measured on the occlusal and proximal margins of the replica. The inlays were then cemented using resin cement (Panavia F2.0) and subjected to two million thermomechanical cycles in water (200 N load and 3.8-Hz frequency). The restored teeth were then cut into beams, using a lathe, for microtensile testing. The contact angles, marginal integrity, and surface patterns after etching were also observed. Statistical analysis was performed using two-way repeated measures analysis of variance (p<0.05), the Tukey test for internal fit and marginal adaptation, and the Student t-test for bond strength. The failure types (adhesive or cohesive) were classified on each fractured beam. The results showed that the misfit of the pulpal walls (p=0.0002) and the marginal adaptation (p=0.0001) of the feldspathic ceramic were significantly higher when compared to those of the polymer-infiltrated ceramic, while the bond strength values of the former were higher when compared to those of the latter. The contact angle of the polymer-infiltrated ceramic was also higher. In the present study, the hybrid ceramic presented improved internal and marginal adaptation, but the bond strengths were higher for the feldspathic ceramic.


Long noncoding RNA LINC00324 promotes retinoblastoma progression by acting as a competing endogenous RNA for microRNA-769-5p, thereby increasing STAT3 expression.
Long intergenic non-protein-coding RNA 324 (LINC00324) is abnormally expressed in multiple human cancer types and plays an important role in cancer initiation and progression. This study showed that LINC00324 was expressed at higher levels in retinoblastoma (RB) tumors and cell lines than in control samples. Increased LINC00324 expression closely correlated with the TNM stage, optic nerve invasion, and shorter overall survival among patients with RB. The knockdown of LINC00324 decreased RB cell proliferation, colony formation, migration, and invasion, and promoted apoptosis and cell cycle arrest in vitro as well as hindered tumor growth in vivo. With respect to the mechanism, LINC00324 acted as a competing endogenous RNA for microRNA-769-5p (miR-769-5p) in RB cells. The mRNA of signal transducer and activator of transcription 3 (STAT3) was identified as a direct target of miR-769-5p in RB cells. Rescue experiments indicated that restoration of STAT3 expression attenuated the tumor-suppressive actions of miR-769-5p in RB cells. Downregulation of miR-769-5p or restoration of STAT3 almost completely reversed the effects of LINC00324 knockdown on RB cells. Our findings describe a novel RB-related LINC00324-miR-769-5p-STAT3 axis that is implicated in the malignancy of RB in vitro and in vivo. This study may point to innovative therapeutic targets in RB.


The design and clinical development of inhibitors of glycosphingolipid synthesis: will invention be the mother of necessity?
The treatment of glycosphingolipid storage diseases by synthesis inhibition was first proposed 40 years ago as an alternative approach to enzyme replacement therapy. We have pursued this strategy through the rational design of potent and selective inhibitors of glucosylceramide synthase, the first step in glycosphingolipid synthesis. Eliglustat tartrate was the result of these efforts and is currently the focus of phase 3 trials for type 1 Gaucher disease. Phase 2 studies showed a reduction in splenomegaly and hepatomegaly and improvements of anemia and thrombocytopenia at levels equivalent to or exceeding the historic response to imiglucerase. Structural analogues of eliglustat have also been designed that lack pgp-1 recognition and cross the blood brain barrier. These may have utility for central nervous system- based sphingolipidoses. Because glycosphingolipids are important regulators of receptor tyrosine kinases, glucosylceramide synthase inhibitors may also be beneficial for disorders such as type 2 diabetes mellitus and polycystic kidney disease.


Valsalva maculopathy: To treat or not to treat.
To discuss diagnostic strategies and management options in cases with suspected valsalva maculopathy (VM), to optimize visual outcome. We describe six cases with suspected VM. The preretinal hemorrhage resolved spontaneously in four out of six patients, without any intervention. One patient underwent neodymium-doped yttrium aluminum garnet hyaloidotomy and the other proceeded to have a vitrectomy for persistent diffuse vitreous hemorrhage. Considering the evidence available and the outcomes of our patients, we have devised a treatment algorithm for treating VM, which is elaborated in this article.


Particle size analysis of municipal solid waste for treatment process modeling.
Several unit operations used in municipal solid waste (MSW) processing facilities are based on physical properties of the waste materials, such as particle size, density and shape. Reliable expressions describing particle size distribution (PSD) of the different waste components present in MSW are not readily available in the context of process modeling. In this study, the characterization data for household wastes and construction and demolition (C&D) wastes were analysed with the purpose of selecting the most representative PSD expression for these waste streams. The Rosin-Rammler distribution was identified over the log-normal and the gamma distributions as the best-fitting PSD for the waste samples. This was demonstrated for both raw and processed waste samples. Parameters were derived and validated for every category of MSW materials considered in the characterization. A model for mixed household waste PSD was developed based on the summation of Rosin-Rammler expressions corresponding to each category of waste materials, as the composition was determined to be the main factor influencing particle size. A simplified model was also derived for mixed waste as a bimodal distribution since two main modes were observed in household waste - one for the "organic" fraction and one for the "inorganic" fraction.


[Clinical Investigation of the Effects of Filgrastim BS1 on Neutropenia Following Oral Cancer Chemotherapy (TPF Therapy)].
The time for the neutrophil count to recover after subcutaneous injection of filgrastim BS1 or lenograstim was studied in patients suffering from neutropenia following preoperative combined chemotherapy using docetaxel, nedaplatin, or cisplatin (in divided doses for 5 days)and 5-fluorouracil for oral cancer. 1. There was no significant difference in the minimum leukocyte and neutrophil counts after chemotherapy. 2. There was no significant difference in the maximum leukocyte and neutrophil counts after chemotherapy. 3. Time for leukocytes to recover from their minimum count(>4,000/mm3)or for neutrophils to recover from their minimum count(>2,000/mm3)and the number of days on which treatment was administered tended to be shorter in the filgrastim BS1 group. Thus, it was concluded that filgrastim BS1 is just as effective as other prior G-CSF agents in treating patients suffering from neutropenia following chemotherapy(TPF therapy).


A CLINICAL STUDY OF ISONIAZID INACTIVATION.
The rate of inactivation of isoniazid (INH) in a host organism varies widely, probably because of genetic factors. A simple chemical test was used to determine INH levels in 24 tuberculous patients three and six hours after oral administration of the drug. Results are expressed in terms of half-life values of free INH in the body. Seven of the 24 patients inactivated INH rapidly (half-life average: 64 minutes); the remaining 17 metabolized INH at a slower rate (half-life average: 186 minutes). The range of individual half-life values was 30 to 305 minutes. A provisional half-life limit of 110 minutes was used to define "fast inactivators"; 110-160 minutes, "moderate inactivators"; and over 160 minutes, "slow inactivators". Although INH inactivation may not be directly related to therapeutic failure, the security margin of the treatment may be diminished in those patients who inactivate INH rapidly.


Mutual interaction of kisspeptin, estrogen and bone morphogenetic protein-4 activity in GnRH regulation by GT1-7 cells.
Reproduction is integrated by interaction of neural and hormonal signals converging on hypothalamic neurons for controlling gonadotropin-releasing hormone (GnRH). Kisspeptin, the peptide product of the kiss1 gene and the endogenous agonist for the GRP54 receptor, plays a key role in the regulation of GnRH secretion. In the present study, we investigated the interaction between kisspeptin, estrogen and BMPs in the regulation of GnRH production by using mouse hypothalamic GT1-7 cells. Treatment with kisspeptin increased GnRH mRNA expression and GnRH protein production in a concentration-dependent manner. The expression levels of kiss1 and GPR54 were not changed by kisspeptin stimulation. Kisspeptin induction of GnRH was suppressed by co-treatment with BMPs, with BMP-4 action being the most potent for suppressing the kisspeptin effect. The expression of kisspeptin receptor, GPR54, was suppressed by BMPs, and this effect was reversed in the presence of kisspeptin. It was also revealed that BMP-induced Smad1/5/8 phosphorylation and Id-1 expression were suppressed and inhibitory Smad6/7 was induced by kisspeptin. In addition, estrogen induced GPR54 expression, while kisspeptin increased the expression levels of ERα and ERβ, suggesting that the actions of estrogen and kisspeptin are mutually enhanced in GT1-7 cells. Moreover, kisspeptin stimulated MAPKs and AKT signaling, and ERK signaling was functionally involved in the kisspeptin-induced GnRH expression. BMP-4 was found to suppress kisspeptin-induced GnRH expression by reducing ERK signaling activity. Collectively, the results indicate that the axis of kisspeptin-induced GnRH production is bi-directionally controlled, being augmented by an interaction between ERα/β and GPR54 signaling and suppressed by BMP-4 action in GT1-7 neuron cells.


Orthodontic Management of Multiple Dilacerations.
Orthodontic alignment of un-erupted dilacerated teeth is challenging, as the bent roots resist forces applied to move them through the bone. Various treatment options are now available to treat this condition including providing prosthesis after extractions and apicectomies. However, to maintain alveolar bone in the area of the un-erupted tooth, especially if the involved tooth is in the anterior segment, the ideal treatment would be to try and bring the tooth in the arch orthodontically. Treatment requires increased time duration, compliance of the patient, and consistent force mechanics. This case report is of a 9-year boy with un-erupted and dilacerated teeth. Orthodontic treatment of prolonged duration was provided to bring these teeth into the arch, improving the esthetics and function.


[Improved control of hypertension and its effect on graft function in children after renal transplantation].
Hypertension in patients after renal transplantation (RTx) is associated with impaired graft functions and graft survival. Control of hypertension in children after RTx is low--only 20-50 % of children have well controlled hypertension. The aim of this interventional study is to improve blood pressure control and to investigate whether the improved control will improve the graft survival. 36 children after RTx (mean age 13.9 +/- 4.4 years, time after RTx 2.7 +/- 2.4) fulfilled the inclusion criteria. Ambulatory blood pressure monitoring (ABPM) and graft function were examined. In children with uncontrolled hypertension, the dose and number of antihypertensive drugs were increased to reach BP <95th centile. ABPM was repeated after 12 months. After 12 months day-time and night-time BP dropped non-significantly, however prevalence of uncontrolled hypertension improved significantly from 42 % to 34 % (p<0.05). Number of antihypertensive drugs increased from 2.1 +/- 0.9 to 2.4 +/- 0.8 drugs per patient (p<0.05), namely that of ACE-inhibitors (from 19% to 27%, p<0.05). Graft function decreased by 3.6 ml/min/1.73m2/year (p<0.05). This 12 months interventional trial demonstrated that control of hypertension in children after RTx can be improved by increasing number of prescribed antihypertensive drugs. The decline of graft function was lower comparing with previous trials.


Dynamic and spatial features of the inhibitory pallidal GABAergic synapses.
The globus pallidus, one of the basal ganglia nuclei, plays a major role in both basal ganglia physiology and pathophysiology. The globus pallidus is innervated mainly by striatal spiny neurons and globus pallidus collaterals. These GABAergic synapses constitute 90% of the input to globus pallidus cells. Despite the dominance of this inhibitory GABAergic input, globus pallidus cells are spontaneously active and most of them increase their firing rate in a task related manner. To explain this apparent inconsistency, we studied the dynamic and spatial effects of GABAergic inputs to globus pallidus neurons. To this end, we used intra-cellular recording from globus pallidus neurons in rat brain slices, investigating the effect of bath and local GABA application, as well as the responses to electrical stimulation of the striatum. We showed that the properties of the responses to either local or global GABA applications are similar to the responses of globus pallidus cells to GABA release from nerve terminals. Since the stimulus-evoked responses have been shown to be inhibitory in nature, we concluded that GABAergic inputs to globus pallidus both at soma and dendrite level are inhibitory. Furthermore, we showed that GABA can promote globus pallidus synchronization by affecting the timing of globus pallidus spiking, and that the globus pallidus GABAergic synapse undergoes rapid frequency-dependent depression. This prominent synaptic depression can account for the ability of globus pallidus neurons to fire in the presence of a majority of inhibitory inputs and might indicate that globus pallidus neurons are tuned to detect frequency changes. Furthermore, globus pallidus synaptic depression rules out the possibility of activation of GABAeregic afferents as the main mechanisms of high-frequency deep brain stimulation, used for treatment of severe parkinsonian patients.


Recruitment of ethnic and socio-economically disadvantaged students into dentistry.
A program designed to attract and graduate underrepresented minorities and disadvantaged students in dentistry is reported. The program consisted of three phases: career orientation, recruitment, and academic enrichment/retention. In the six years of this program's existence, the number of minority students enrolled increased from 1 to 28, including 12 who were graduated by June 1979. Only two were lost because of academic difficulties. An analysis of grades and tutorial needs showed that students experienced the most difficulty with first-year basic science courses. Recommendations are presented for program improvement.


Metabolic impact of a nutrition education program for the promotion of fruit and vegetable consumption with people with severe mental disorders (DIETMENT).
The aim of this study is to determine the metabolic impact of a nutrition education program on metabolic parameters and the presence of metabolic syndrome (MetS). Seventy-four patients were included (mean age, 48.7 years [Standard deviation, SD: 10.8], 55.4% men). The diagnoses of SMD were 37.8% schizophrenia and related disorders; 29.7% bipolar disorder; 25.7% depressive disorder; 4.1% personality disorders; and 2.7% obsessive compulsive disorders. Thirty-seven individuals were distributed in both the intervention group (IG) and the control group (CG). In the IG the presence of MetS was 56.3% and in the CG 46.7%, with no statistically significant difference (p = 0.309). At the end of the study, glomerular filtrate decreased in the IG, body mass index and abdominal perimeter increased in both groups, and there were no changes in metabolic parameters between the groups. Between the baseline and the end of the study, there was no increase in the number of patients diagnosed with MetS (14 at both points); and in the CG the increase was from 8 to 12 (p = 0.005). An intervention based on fruit and vegetable intake could prevent progression to MetS in individuals with SMD, decreasing the likelihood of cardiovascular disease. Trial registration The trial was retrospectively registered on International Standard Randomised Controlled Trial Number (ISRCTN) Register on 11 March 2022 (ISRCTN12024347).


Plug-and-play fluorophores extend the spectral properties of Spinach.
Spinach and Spinach2 are RNA aptamers that can be used for the genetic encoding of fluorescent RNA. Spinach2 binds and activates the fluorescence of (Z)-4-(3,5-difluoro-4-hydroxybenzylidene)-1,2-dimethyl-1H-imidazol-5(4H)-one (DFHBI), allowing the dynamic localizations of Spinach2-tagged RNAs to be imaged in live cells. The spectral properties of Spinach2 are limited by DFHBI, which produces fluorescence that is bluish-green and is not optimized for filters commonly used in fluorescence microscopes. Here we characterize the structural features that are required for fluorophore binding to Spinach2 and describe novel fluorophores that bind and are switched to a fluorescent state by Spinach2. These diverse Spinach2-fluorophore complexes exhibit fluorescence that is more compatible with existing microscopy filter sets and allows Spinach2-tagged constructs to be imaged with either GFP or YFP filter cubes. Thus, these "plug-and-play" fluorophores allow the spectral properties of Spinach2 to be altered on the basis of the specific spectral needs of the experiment.


[Euthanasia - an attempt to organize issue].
This article is an attempt to complete and holistically discuss problem of euthanasia, especially its ethical and legal aspects, comparing to Polish law. The subject of euthanasia arouse interest of the society because it touches one of the most important aspects of life, which is the death. Even bigger emotions are aroused amongst physicians. They are forced to put on the line the life as biggest value on the one side and autonomy of human being on the other. It also touches the empathy for suffering. The euthanasia was divided into three forms: active euthanasia, passive euthanasia and assisted suicide. Any form of euthanasia is illegal in Poland according to both the Penal Code and Code of Medical Ethics. Range of possible penal consequences perpetrator is very wide from waiver of punishment to life imprisonment and it comes from different penal qualification of the euthanasia. Qualification of the euthanasia is based on terms of intent of perpetrator's act, request of patient, strong empathy for suffering if the patient and decision based on up-to-date medical knowledge. It is valuable to mention "do-not-resuscitate" DNR procedure, which in case of medical futility is legally accepted in Poland, but in other form may be qualified as passive euthanasia.


Fragmentation dynamics of condensed phase thymine by low-energy (10-200 eV) heavy-ion impact.
We report measurements of the formation and desorption of ionic fragments induced by very low-energy (10-200 eV) Ar(+) irradiation of thymine (T) films, deposited on a polycrystalline Pt substrate. A multitude of dissociation channels is observed, among which the major cation species are identified as HNCH(+), HNC(3)H(4) (+), C(3)H(3) (+), OCNH(2) (+), [T-OCN](+), [T-OCNH(2)](+), [T-O](+), and [T+H](+) and the major anions as H(-), O(-), CN(-),and OCN(-). Cation fragment desorption appears at much lower threshold energies (near 15 eV) than anion fragment desorption, where the latter depends strongly on the film thickness. It is proposed that anion fragment formation and desorption results from projectile impact-induced excitation of either (1) a neutral thymine molecule, followed by fragmentation and charge exchange between the energetic neutral fragment and the substrate (or film) and/or (2) a deprotonated monoanionic thymine molecule to a dissociative state, followed by a unimolecular fragmentation of the excited thymine anion. The H(-) and O(-) fragment formations may have a further contribution from dipolar dissociation, e.g., formation of electronically excited neutral thymine, followed by dissociation into O(-)+[T-O](+), due to their reduced sensitivity to the film thickness. Positive-ion fragment desorption exhibits no significant dependence on film thickness before the emergence of surface charging, and originates from a kinetically assisted charge-transfer excitation. The results suggest that the potential energy of the incident ion plays a significant role in lowering the threshold energy of kinetic fragmentation of thymine. Measurements of the time-dependent film degradation yields for 100-eV Ar(+) suggest a quantum efficiency for degradation of about six thymine molecules per incident ion.


One-electron oxidation of plasmid DNA by selenium(V) species.
To employ the gamma-radiation-generated selenium(V) one-electron-oxidizing agent SeO3*- for the preparation of guanyl radicals in plasmid DNA, and to compare the behaviour of this reagent with that of other similarly reactive oxidant species. Plasmid DNA in aerobic aqueous solution was irradiated with 137Cs gamma-rays (662 keV). The solutions also contained up to 4x10(-2) mol x dm(-3) sodium selenate (Na2SeO4) and/or up to 10(-1) mol x dm(-3) sodium biselenite (NaHSeO3), as well as auxiliary scavengers such as DMSO or glycerol. In some cases, reducing agents such as ferrocyanide were also present. After irradiation, the plasmid was incubated with the Escherichia coli base excision-repair endonuclease formamidopyrimidine-DNA N-glycosylase (FPG). These treatments produced strand breaks in the plasmid. The yields of these strand breaks were quantified by agarose gel electrophoresis. In general, gamma-irradiation produced single-strand breaks (SSB) in plasmid DNA. Subsequent incubation with the endonuclease FPG increased the SSB yield by a factor of 2-100-fold. The smallest effects of FPG were observed when only DMSO or glycerol were present during irradiation. FPG incubation produced significantly larger increases in the SSB yield after gamma-irradiation in the additional presence of selenate and/or biselenite. The largest effect of FPG was observed after gamma-irradiation in the presence of 10(-2) mol x dm(-3) sodium selenate and 10(-1) mol x dm(-3) glycerol. This was indicative of extensive oxidative damage to the plasmid under these conditions and provided evidence for guanine oxidation mediated by SeO3*-. The large effect of FPG was strongly attenuated by the addition of reducing agents such as ferrocyanide. The observations suggest that these reducing agents exert their effects through the reduction of an intermediate guanyl radical. By comparing the yields of breaks produced after gamma-irradiation under a range of conditions, it is possible to formulate a reaction scheme that describes the chemical reactions responsible for the formation of strand breaks and FPG-sensitive sites. By applying this scheme to the data, we can quantify rate constants for the reduction of DNA guanyl radicals by reducing agents. This reaction is of particular interest to radiation biology because it is the equivalent of the repair of DNA damage by the direct effect of ionizing radiation.


Estimation of seismic velocities of upper oceanic crust from ocean bottom reflection loss data.
This paper describes a Bayesian inversion of acoustic reflection loss versus angle measurements to estimate the compressional and shear wave velocities in young uppermost oceanic crust, Layer 2A. The data were obtained in an experiment on the thinly sedimented western flank of the Endeavor segment of the Juan de Fuca Ridge, using a towed horizontal hydrophone array and small explosive charges as sound sources. Measurements were made at three sites at increasing distance from the ridge spreading center to determine the effect of age of the crust on seismic velocities. The inversion used reflection loss data in a 1/3-octave band centered at 16 Hz. The compressional and shear wave velocities of the basalt were highly sensitive parameters in the inversion. The compressional wave velocity increased from 2547 + or - 30 to 2710 + or - 18 m/s over an age span of 1.4 million years (Ma) from the spreading center, an increase of 4.5 + or - 1.0%/Ma. The basalt shear wave velocity increased by nearly a factor of 2, from approximately 725 to 1320 m/s over the same age span. These results show a decreasing trend of Poisson's ratio with age, from a value of 0.46 at the youngest site closest to the ridge axis.


Can mobile-health applications contribute to long-term increase in physical activity after medical rehabilitation?-A pilot-study.
Due to the positive effects of rehabilitation declining over time, the aim of this study was to investigate the long-term physical activity level (PAL) following inpatient rehabilitation in relation to the use of a smartphone-based after-care program. 202 patients (mean Body Mass Index (BMI): 30,8 kg/m2; 61% female) with chronic diseases (e.g., diabetes mellitus, obesity, chronic low back pain, depression) were recruited between 08/2020 and 08/2021 in this single-arm observational study. All patients underwent a 3-week inpatient rehabilitation program. PAL (in total activity minutes/week) was measured with a validated (online) questionnaire (Freiburger Questionnaire on PA) after 3, 6, 9, and 12 months. App usage (online time, completion of a course) was recorded automatically and used to evaluate the app user behavior (adherence). A variety of socio-economic factors (age, sex, education level, income etc.) were collected to identify possible barriers of app use. Except for sex, no significant difference was observed for socio-economic factors regarding app usage behavior. Median PAL significantly increased after rehabilitation in the total cohort from 360 min/week (before rehabilitation) to 460 min/week 6 months after rehabilitation, then declined to 420 min/week 9 months after rehabilitation before falling below baseline level after 12 months. There was no significant difference in PAL between app users (45%, 91/202) and non-users (55%, 111/202), although app users tended to retain higher activity levels after 3 and 6 months, respectively. Overall, our study emphasizes the effectiveness of a 3-week rehabilitation program on PAL and the acceptance and usability of a smartphone-based after-care program in this patient group. The adherence to this 3-months after-care app program was acceptable (30%), with modest evidence supporting the effectiveness of app use to sustain PAL in the short term.


Decoding Immune Heterogeneity of Triple Negative Breast Cancer and Its Association with Systemic Inflammation.
Triple negative breast cancer (TNBC) is an aggressive subtype with limited therapeutic options. New opportunities are emerging from current comprehensive characterization of tumor immune infiltration and fitness. Therefore, effectiveness of current chemotherapies and novel immunotherapies are partially dictated by host inflammatory and immune profiles. However, further progress in breast cancer immuno-oncology is required to reach a detailed awareness of the immune infiltrate landscape and to determine additional reliable and easily detectable biomarkers. In this study, by analyzing gene expression profiles of 54 TNBC cases we identified three TNBC clusters displaying unique immune features. Deep molecular characterization of immune cells cytolytic-activity and tumor-inflammation status reveled variability in the local composition of the immune infiltrate in the TNBC clusters, reconciled by tumor-infiltrating lymphocytes counts. Platelet-to-lymphocyte ratio (PLR), a blood systemic parameter of inflammation evaluated using pre-surgical blood test data, resulted negatively correlated with local tumoral cytolytic activity and T cell-inflamed microenvironment, whereas tumor aggressiveness score signature positively correlated with PLR values. These data highlighted that systemic inflammation parameters may represent reliable and informative markers of the local immune tumor microenvironment in TNBC patients and could be exploited to decipher tumor infiltrate properties and consequently to select the most appropriate therapies.


[The secondary structure of amides of adenylic acid containing D- and L-aromatic amino acids].
Adenylyl-(5'leads to N)-amino acids containing as amino components, methyl esters of D-, L- and DL-phenylalanine, D-, L- and DL-tyrosine, and D-, L- and DL-tryptophan have been investigated by proton magnetic resonance (PMR) spectroscopy and circular dichroism (CD). The temperature and pD dependences of proton chemical shifts of these compounds have been studied. These data, together with the magnitudes of the upfield chemical shifts of the PMR signals of adenine and aromatic amino acids residues in adenylyl-(5'leads to N)-amino acids, have enabled us to construct conformational models of these compounds. The proposed conformation has been substantiated by the CD results. It is shown that in adenylyl-(5'leads to N)-amino acids the planes of adenine and amino acid aromatic moieties are roughly parallel. The aromatic rings of phenylalanine and tyrosine are localized approximately above the centre of adenine. In adenylyl-(5'leads to N)-D, -(L)-tryptophan, the six-membered rings of the indole overlaps the five-membraned ring of adenine indole partially overlaps the six-membered ring of adenine. A difference in the non-covalent interactions of D- and L-amino acids with nucleotides has been revealed. The mutual localization of the aromatic systems of AMP and the amino acids and also the positions of -OCH3 group with respect to the centre of the amino acid aromatic moiety differs in the series of the studied nucleotide derivatives of D- and L-amino acids.


X-ray phase-contrast tomography of renal ischemia-reperfusion damage.
The aim of the study was to investigate microstructural changes occurring in unilateral renal ischemia-reperfusion injury in a murine animal model using synchrotron radiation. The effects of renal ischemia-reperfusion were investigated in a murine animal model of unilateral ischemia. Kidney samples were harvested on day 18. Grating-Based Phase-Contrast Imaging (GB-PCI) of the paraffin-embedded kidney samples was performed at a Synchrotron Radiation Facility (beam energy of 19 keV). To obtain phase information, a two-grating Talbot interferometer was used applying the phase stepping technique. The imaging system provided an effective pixel size of 7.5 µm. The resulting attenuation and differential phase projections were tomographically reconstructed using filtered back-projection. Semi-automated segmentation and volumetry and correlation to histopathology were performed. GB-PCI provided good discrimination of the cortex, outer and inner medulla in non-ischemic control kidneys. Post-ischemic kidneys showed a reduced compartmental differentiation, particularly of the outer stripe of the outer medulla, which could not be differentiated from the inner stripe. Compared to the contralateral kidney, after ischemia a volume loss was detected, while the inner medulla mainly retained its volume (ratio 0.94). Post-ischemic kidneys exhibited severe tissue damage as evidenced by tubular atrophy and dilatation, moderate inflammatory infiltration, loss of brush borders and tubular protein cylinders. In conclusion GB-PCI with synchrotron radiation allows for non-destructive microstructural assessment of parenchymal kidney disease and vessel architecture. If translation to lab-based approaches generates sufficient density resolution, and with a time-optimized image analysis protocol, GB-PCI may ultimately serve as a non-invasive, non-enhanced alternative for imaging of pathological changes of the kidney.


Changes in lung perfusion scintigraphy and pulmonary function tests in irradiated breast cancer patients.
To investigate the utility of quantitative lung perfusion scintigraphy and pulmonary function tests in the assessment of radiation-induced lung injury. The prospective study was conducted at Zonguldak Bulent Ecevit University Hospital, Turkey, from May 2012 to October 2016, and comprised female breast cancer patients having undergone lung perfusion scintigraphy with Tc-99m macroaggregated albumin before and after radiotherapy. Pulmonary function tests and carbon monoxide diffusing capacity tests were also carried out on all the patients, and the relationship between treatment-related changes and its association with radiotherapy doses was analysed. Data was analysed using SPSS 19. There were 43 patients with a median age of 49 (interquartile range: 32-71 years). Carbon monoxide diffusing capacity values at baseline showed a significant decrease at 6 and 12 months post- radiotherapy (p<0.05), while none of the parameters of the pulmonary function tests showed a significant difference (p>0.05). Also, the median percentage of perfusion studies in the irradiated lung decreased significantly (p<0.001) at 12 months post-treatment. There was significant reduction in perfusion studies of irradiated lungs (p<0.05). Carbon monoxide diffusing capacity and quantitative lung perfusion scintigraphy were found to be useful tools for the early diagnosis and monitoring of radiation-induced lung injury.


Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase 1/cyclin B.
Tuberous sclerosis complex is a tumor suppressor gene syndrome whose manifestations can include seizures, mental retardation, and benign tumors of the brain, skin, heart, and kidneys. Hamartin and tuberin, the products of the TSC1 and TSC2 genes, respectively, form a complex and inhibit signaling by the mammalian target of rapamycin. Here, we demonstrate that endogenous hamartin is threonine-phosphorylated during nocodazole-induced G2/M arrest and during the G2/M phase of a normal cell cycle. In vitro assays showed that cyclin-dependent kinase 1 phosphorylates hamartin at three sites, one of which (Thr417) is in the hamartin-tuberin interaction domain. Tuberin interacts with phosphohamartin, and tuberin expression attenuates the phosphorylation of exogenous hamartin. Hamartin with alanine mutations in the three cyclin-dependent kinase 1 phosphorylation sites increased the inhibition of p70S6 kinase by the hamartin-tuberin complex. These findings support a model in which phosphorylation of hamartin regulates the function of the hamartin-tuberin complex during the G2/M phase of the cell cycle.


A spectroscopic and molecular dynamic approach on the interaction between ionic liquid type gemini surfactant and human serum albumin.
The interactions of imidazolium bashed ionic liquid-type cationic gemini surfactant ([C12-4-C12im]Br2) with HSA were studied by fluorescence, time-resolved fluorescence, UV-visible, circular dichroism, molecular docking and molecular dynamic simulation methods. The results showed that the [C12-4-C12im]Br2 quenched the fluorescence of HSA through dynamic quenching mechanism as confirmed by time-resolved spectroscopy. The Stern-Volmer quenching constant (Ksv) and relevant thermodynamic parameters such as enthalpy change (ΔH), Gibbs free energy change (ΔG) and entropy change (ΔS) for interaction system were calculated at different temperatures. The results revealed that hydrophobic forces played a major role in the interactions process. The results of synchronous fluorescence, UV-visible and CD spectra demonstrated that the binding of [C12-4-C12im]Br2 with HSA induces conformational changes in HSA. Inquisitively, the molecular dynamics study contribute towards understanding the effect of binding of [C12-4-C12im]Br2 on HSA to interpret the conformational change in HSA upon binding in aqueous solution. Moreover, the molecular modelling results show the possible binding sites in the interaction system.


[Fallot's tetralogy with severe symptomatology during the first year of life (author's transl)].
Seventeen cases of Fallot's Tetralogy with severe symptomatology during the first year of life are reviewed. In all of them, a cardiac catheterization and angiocardiography were performed. In 2 cases the pulmonary outflow tract was atretic. In general, the clinical, radiologic, electrocardiographic and hemodynamic findings were similar to those previously reported, although in 3 patients of the present series atypical electrocardiographic findings were found. Pronounced narrowing and horizontal orientation of the infundibular chamber, and accentuated hypoplasia of the pulmonary artery branches and of the left heart cavities and were all unfavourable findings for total correction frequently found in the present material. Minimal or non-existent aortic dextroposition was observed in association with cases of Fallot's Tetralogy with extreme severity. Surgery was indicated as an emergency measure in the majority of the cases. Palliatives procedures were performed in 10 patients, and corrective surgery in one. Surgical results agree with the extreme severity that this lesion has, when it gives rise to important symptomatology so early in the life.


Divide and conquer: the Pseudomonas aeruginosa two-component hybrid SagS enables biofilm formation and recalcitrance of biofilm cells to antimicrobial agents via distinct regulatory circuits.
The opportunistic pathogen Pseudomonas aeruginosa forms antimicrobial resistant biofilms through sequential steps requiring several two-component regulatory systems. The sensor-regulator hybrid SagS plays a central role in biofilm development by enabling the switch from the planktonic to the biofilm mode of growth, and by facilitating the transition of biofilm cells to a highly tolerant state. However, the mechanism by which SagS accomplishes both functions is unknown. SagS harbours a periplasmic sensory HmsP, and phosphorelay HisKA and Rec domains. SagS domain was used as constructs and site-directed mutagenesis to elucidate how SagS performs its dual functions. It was demonstrated that HisKA-Rec and the phospho-signalling between SagS and BfiS contribute to the switch to the biofilm mode of growth, but not to the tolerant state. Instead, expression of SagS domain constructs harbouring HmsP rendered ΔsagS biofilm cells as recalcitrant to antimicrobial agents as wild-type biofilms, likely by restoring BrlR production and cellular c-di-GMP levels to wild-type levels. Restoration of biofilm tolerance by HmsP was independent of biofilm biomass accumulation, RsmA, RsmYZ, HptB and BfiSR-downstream targets. Our findings thus suggest that SagS likely makes use of a "divide-and-conquer" mechanism to regulate its dual switch function, by activating two distinct regulatory networks via its individual domains.


Expectation values in the Lieb-Liniger Bose gas.
We present a novel method to compute expectation values in the Lieb-Liniger model both at zero and finite temperature. These quantities, relevant in the physics of one-dimensional ultracold Bose gases, are expressed by a series that has a remarkable behavior of convergence. Among other results, we show the computation of the three-body expectation value at finite temperature, a quantity that rules the recombination rate of the Bose gas.


Two epizootic Perkinsus spp. events in commercial oyster farms at Santa Catarina, Brazil.
Perkinsus spp. have been detected in various bivalve species from north-east Brazil. Santa Catarina is a South Brasil state with the highest national oyster production. Considering the pathogenicity of some Perkinsus spp., a study was carried out to survey perkinsosis in two oyster species cultured in this State, the mangrove oyster Crassostrea gasar and the Pacific oyster Crassostrea gigas. Sampling involved eight sites along the state coast, and oyster sampling was collected during the period between January 2013 and December 2014. For the detection of Perkinsus, Ray's fluid thioglycollate medium (RFTM) and histology were used, and for the identification of the species, PCR and DNA sequencing were used. Perkinsus spp. was found by RFTM in C. gigas and C. gasar from São Francisco do Sul. This pathology was also detected in C. gasar from Balneário Barra do Sul both, by RFTM and histology. Perkinsus marinus was identified in C. gigas and C. gasar from São Francisco do Sul and Perkinsus beihaiensis in C. gasar from Balneário Barra do Sul. This is the first report of P. marinus in C. gigas from South America. Results of this preliminary study suggest that both oyster species tolerate the species of Perkinsus identified, without suffering heavy lesions.


Clinical and allergological analysis of ocular manifestations of sick building syndrome.
The disease concept of sick building syndrome (SBS) is still unclear. Ocular mucous membrane irritation is one of the major symptoms of SBS. However, the immunological aspects of the ocular complications of SBS are not yet clarified. The clinical and allergological aspects of SBS cases with ocular disorders with special reference to allergic conjunctival diseases (ACD) were analyzed, especially with respect to local immunological features. Twelve cases of SBS with ocular findings and 49 cases of ACD (allergic conjunctivitis [AC], atopic keratoconjunctivitis [AKC], and vernal keratoconjunctivitis [VKC]) for comparison were evaluated. The clinical findings in SBS and ACD were scored, and tear film breakup time (BUT) was measured. Cytokine (interferon-γ [IFN-γ], interleukin [IL]-2, IL-4, IL-5, IL-6, IL-8, and IL-13) concentrations in tears were analyzed by cytometric bead arrays. Eosinophil count in peripheral blood, total IgE in serum, and multiple allergen simultaneous test (MAST) for antigen-specific IgE were also measured. In SBS, conjunctival lesions were observed in all cases, and corneal abnormalities were found in two-thirds of the cases. Limbal lesions were observed in 2 pediatric cases. Mean serum total IgE level in SBS was significantly higher than that in AC; however, it was significantly lower than that in AKC and VKC. Eosinophil count in peripheral blood and number of positive allergens in MAST were significantly lower in SBS than in AKC and VKC. Significant elevation of tear IL-4 was observed in SBS and ACD. However, in contrast to ACD, elevation of other cytokines in tears was not observed in SBS. Mean tear BUT in SBS was in the normal range. From these results, SBS is thought to be partially induced by an allergic response. However, clinical dissociation of the ocular clinical findings and local immunological features in tear cytokines may suggest that SBS belongs to a different entity from ACD.


In Situ Monitoring of Mitochondria Regulating Cell Viability by the RNA-Specific Fluorescent Photosensitizer.
Cell viability is greatly affected by external stimulus eliciting correlated dynamical physiological processes for cells to choose survival or death. A few fluorescent probes have been designed to detect whether the cell is in survival state or apoptotic state, but monitoring the regulation process of the cell undergoing survival to death remains a long-standing challenge. Herein, we highlight the in situ monitor of mitochondria regulating the cell viability by the RNA-specific fluorescent photosensitizer L. At normal conditions, L anchored mitochondria and interacted with mito-RNA to light up the mitochondria with red fluorescence. With external light stimulus, L generated reactive oxide species (ROS) and cause damage to mitochondria, which activated mitochondrial autophagy to prevent death, during which the red fluorescence of L witnessed dynamical distribution in accordance with the evolution of vacuole structures containing damaged mitochondria into autophagosomes. However, with ROS continuously increasing, the mitochondrial apoptosis was eventually commenced and L with red fluorescent was gradually accumulated in the nucleoli, indicating the programmed cell death. This work demonstrated how the delicate balance between survival and death are regulated by mitochondria.


Lower risk of hypoglycemia with sitagliptin compared to glipizide when either is added to metformin therapy: a pre-specified analysis adjusting for the most recently measured HbA(1c) value.
In a previously-published study, adding sitagliptin or glipizide to ongoing metformin therapy provided similar HbA(1c) improvement (both groups, -0.7%) after 52 weeks in patients with type 2 diabetes (T2DM). Significantly fewer patients experienced symptomatic hypoglycemia with sitagliptin (5% of 588 patients) compared to glipizide (32% of 584 patients). Glycemic efficacy and patient characteristics may influence hypoglycemic events. The present analysis evaluated the risk of hypoglycemia with sitagliptin or glipizide after adjusting for the most recently measured HbA(1c) value. Data for this analysis were from the aforementioned 52-week, randomized, double-blind, active-controlled study. The primary endpoint was confirmed hypoglycemia (i.e., symptomatic hypoglycemia confirmed with a concurrent fingerstick glucose ≤70 mg/dL [3.9 mmol/L]); the secondary endpoint was severe hypoglycemia (requiring medical or non-medical assistance or symptoms of neuroglycopenia). Complementary log-log regression random effects models with terms for treatment, most recently measured HbA(1c) value, time (i.e., days since randomization), gender, and age (< or ≥65 years) were used to assess adjusted subject-specific treatment effects. Over the full range of HbA(1c) levels and follow-up time, the risk of confirmed hypoglycemic events was lower with sitagliptin compared with glipizide (31 vs. 448 events; adjusted hazard ratio [HR] = 0.05 [95% CI: 0.03, 0.09], p < 0.001). The risk was also lower with sitagliptin in the younger (HR = 0.06 [95% CI: 0.03, 0.12], p < 0.001) and older (HR = 0.02 [0.01, 0.08], p < 0.001) age groups compared with glipizide. For severe hypoglycemia events (2 vs. 22), the risk was lower with sitagliptin (HR = 0.08 [95% CI: 0.01, 0.47]; p = 0.005). The actual time between the HbA(1c) measurement and the hypoglycemic event was variable and not controlled for in the analysis. In pre-specified analyses adjusting for the most recently measured HbA(1c) value, there was a substantial reduction in risk for confirmed hypoglycemia with sitagliptin compared to glipizide when added to ongoing metformin therapy in patients with T2DM. The risk of confirmed hypoglycemia was very low in younger and older patients treated with sitagliptin.


Population-level utilisation of neoadjuvant radiotherapy for the treatment of rectal cancer.
International clinical guidelines recommend long- or short-course neoadjuvant radiotherapy for locally advanced rectal cancer. This study aims to examine variation in the use of neoadjuvant radiotherapy for rectal cancer and identify patient and hospital factors that underpin this variation. We conducted a retrospective, consecutive cohort study using statewide hospitalisation and radiotherapy data from New South Wales, Australia, 2013-2018. Included participants had a primary rectal adenocarcinoma and underwent surgical resection. Factors associated with the use or not of any neoadjuvant radiotherapy, and short versus long-course were explored using multilevel logistic regression models. Of the 2912 people included in the study, 43% received neoadjuvant radiotherapy. There was significant variation in the use of neoadjuvant radiotherapy depending on geographic location. Abdominoperineal excision (odds ratio [OR] = 1.87, 95% confidence interval [CI] = 1.53-2.28) and having surgery in a public hospital (OR = 2.34, 95% CI = 1.92-2.87) were both predictors of use. Among those receiving neoadjuvant radiotherapy, 17% received short-course therapy, with short-course declining over the study period. The use of neoadjuvant radiotherapy for rectal cancer is highly variable, with differences only partially explained by assessable patient-or hospital-level factors. Understanding neoadjuvant radiotherapy utilisation patterns may assist in identifying barriers and opportunities to improve adherence to clinical guidelines.


Linkage of susceptibility to experimental allergic encephalomyelitis to the major histocompatibility locus in the rat.
Experimental allergic encephalomyelitis (EAE) was induced in rats of various genotypes by injection of 10 microg guinea pig basic protein in complete Freund's adjuvant containing 100 microg H(37) RV M. tuberculosis. Histologically verified EAE was present in 20/20 Lewis, 17/17 (Lewis x BN)F(1), 9/9 Lewis backcross, and 21/42 BN backcross rats. Among the BN backcross animals, 25/42 were determined to carry the major histocompatibility type characteristic of the Lewis strain and 21 of these had EAE. Separate groups of Lewis, BN, and (Lewis x BN)F(1) rats were immunized as described and skin tested on day 13 with 10 microg guinea pig basic protein and rat S basic protein. Animals of each genotype had Arthus and delayed skin reactivity to both antigens. These data are compatible with the hypothesis that susceptibility to EAE in rats is controlled by an autosomal dominant gene linked to the major histocompatibility locus. It is proposed that this is an immune response gene, designated Ir-EAE, which controls T cell reactivity directed against a highly encephalitogenic portion of the basic protein molecule.


Qualitative and quantitative evaluation of heart sound reduction from lung sound recordings.
Recursive least squares (RLS) adaptive noise cancellation (ANC) and wavelet transform (WT) ANC have been applied and compared for heart sound (HS) reduction from lung sounds (LS) recordings. Novel processes for quantitative and qualitative evaluation of any method for HS reduction from LS have also been proposed.


Short-term effects of intravitreal ranibizumab therapy on diabetic macular edema.
The short-term effects of intravitreal ranibizumab (IVR) on diabetic macular edema (DME) remains unclear. We assessed the short-term effects of IVR on DME. Eighteen eyes of 14 patients with DME were enrolled in this prospective interventional case series. After intravitreal ranibizumab was injected into treatment-naïve eyes with DME, we measured the foveal thickness (FT) before and 2 h, 1 day, 1 week, and 1 month later and the best-corrected visual acuity (BCVA) at all times except 2 h and compared the changes to baseline (ΔFT and ΔVA). The mean FT decreased significantly (p < 0.0001) from 452 ± 77 to 429 ± 65 microns after 2 h. The mean logarithm of the minimum angle of resolution BCVA improved significantly (p = 0.032) after 1 month from 0.41 ± 0.24 to 0.32 ± 0.21 (20/51 to 20/42, Snellen equivalent). The ΔFT after 2 h was significantly (r = 0.53, p = 0.025) correlated with the ΔFT after 1 month. The ΔVA after 1 day was significantly (r = 0.59, p = 0.01) correlated with the ΔVA after 1 month. The structural effects of IVR for DME occurred within 2 h, whereas the functional effects occurred after 1 month. The short-term effects (within 1 day) of IVR may predict the therapeutic outcome 1 month after IVR in patients with DME. The trial registration number: UMIN000026118 (Feb/13/2017). Retrospectively registered.


Rotaxanated conjugated sensory polymers.
Two highly emissive conjugated polymers with tethered rotaxane repeat units are reported. Hydrogen bonding between acidic alcohols and the N-heteroaromatic groups in the rotaxanes attenuates polymer fluorescence. In addition, the rotaxane groups create precise three-dimensional pockets for metal binding, which results in fluorescence quenching. Exposing thin films of Zn-doped polymers to alcohol vapors reverses the quenching by up to 25%.


Chrysanthemum cutting productivity and rooting ability are improved by grafting.
Chrysanthemum has been commercially propagated by rooting of cuttings, whereas the quality will decline over multiple collections from a single plant. Therefore, we compared the vigour, rooting ability, and some physiological parameters between cuttings harvested from nongrafted "Jinba" (non-grafted cuttings) with those collected from grafted "Jinba" plants onto Artemisia scoparia as a rootstock (grafted cuttings). The yield, length, node number, stem diameter, fresh weight, and dry weight of the grafted cuttings were superior to the non-grafted cuttings. Also grafted cuttings "Jinba" rooted 1 day earlier, but showing enhanced rooting quality including number, length, diameter, and dry weight of roots, where compared to the non-grafted. The physiological parameters that indicated contents of soluble protein, peroxidase activity, soluble sugar, and starch, ratios of soluble sugar/nitrogen ratio, and carbohydrate/nitrogen (C/N), as well as contents of indole-3-acetic acid (IAA) and abscisic acid (ABA), and IAA/ABA ratio were significantly increased in the grafted cuttings. This suggested their important parts in mediating rooting ability. Results from this study showed that grafting improved productivity and rooting ability related to an altered physiology, which provide a means to meet the increasing demand.


Hydrochemical characteristics of natural water and selenium-rich water resources in the Northern Daba Mountains, China.
The Northern Daba Mountains (NDM) of Shaanxi Province, China, are a well-known selenium (Se)-rich area, and the area is also known for endemic fluorine (F) and arsenic (As) poisoning. In order to study the hydrochemical characteristics and trace element contents of the natural waters of this region, 62 water samples were collected from Lan'gao area in the NDM. The hydrochemical composition was principally characterized by Ca·Mg-HCO3·SO4. F and As concentrations ranged from 0.01 to 0.67 mg/L and from 0.33 to 6.29 μg/L, respectively, lower than Chinese national standard and international guidelines for drinking water quality. One year of monitoring proved that F and As in natural water were not the sources of the local fluorosis and arseniasis in the NDM. The average Se concentration in fissure water was 5.20 μg/L. The average Se content of river water was 2.82 μg/L, 14 times that of the world's surface level (0.2 μg/L). The Se content in eight samples reached the Chinese national standards for mineral drinking water quality (>10 μg/L). Contrasting the water samples of May, July, and September in 2015 shows that the Se content is relatively stable and the increase of humidity might be beneficial to increase the content of selenium and strontium in water.


Expression of S100β protein in patients with vascular dementia after basal ganglia hemorrhage and its clinical significance.
We investigated the expression levels and clinical significance of S100β protein in patients with vascular dementia (VD) after basal ganglia hemorrhage. From June 2014 to December 2015, in 138 patients with basal ganglia hemorrhage, we carried out the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) in patients on the day before the operation, the day after the operation and 9 days after the operation. Thirty-two patients (blood vessel group) had cognitive dysfunction and 106 patients (control group) had VD. One hundred thirty-eight cases of healthy adult volunteers were treated in Henan Provincial People's Hospital and were selected in the same period as healthy controls. The expression levels of serum S100β in the three groups were tested through the ELISA method and the statistical analysis was carried out. In VD patients, the serum S100β levels of patients were significantly higher than VD and healthy control groups; differences were statistically significant (P<0.05). However, there was no significant difference between those without VD after operation and the healthy control group (P>0.05). The correlation analysis was carried out with serum S100β as an independent variable and mean arterial pressure, BMI, MMSE and MoCA scores as dependent variables. Our results suggest that S100β expression levels were negatively correlated to the MMSE score (rs=-4.19) and the difference was statistically significant (P<0.05). The length of hospital stay of patients with basal ganglia hemorrhage associated with VD was significantly extended, with a mean of 23.4±2.8 days. The expression levels of S100β protein in the serum of patients with VD after basal ganglia hemorrhage was significantly increased and negatively correlated to the cognitive function of patients. Therefore, it can be used as a differential diagnosis indicator of VD after the basal ganglia hemorrhage and treatment target point of the VD.


Monocytoid B cells. A comparative clinical pathological study of their distribution in different types of low-grade lymphomas.
Neoplastic monocytoid B-cells (MBCs) are present in different amounts in several types of non-Hodgkin's lymphomas (NHLs), including monocytoid B-cell lymphoma (MBCL), splenic marginal zone lymphoma (SMZL), mucosa-associated lymphoid tissue (MALT) low-grade B-cell lymphomas, and follicular centroblastic-centrocytic (CB-CC) lymphomas. In an attempt to clarify the relationships between different groups of tumors with a significant monocytoid component, we studied six primary lymph node MBCL, three SMZL, seven MALT lymphomas, and four CB-CC with monocytoid differentiation. Their clinical, morphological, immunohistochemical and molecular features were compared. The results show wide overlapping between MALT and MBCL in terms of morphology, immunophenotype, and molecular features. Follicular colonization was a characteristic finding in both groups. Some MBCL revealed mucosal involvement during the course of the disease, suggesting a possible MALT origin. Our data support the suggestion that the use of the term MBCL should be discontinued in cases with mucosal involvement, as they are probably examples of lymph node involvement brought about by MALT lymphomas. Although SMZL have some overlapping features with MBCL and MALT lymphomas, some of the clinical and morphological specific findings justify their distinction from the other groups. The CB-CCs with monocytoid differentiation frequently harbored t(14;18), lacking any significant differentiating features from conventional follicular CB-CC lymphomas. Additional studies are needed to define the molecular features of MBCL and other marginal zone tumors.


Targeted genomic analysis of 364 adrenocortical carcinomas.
Despite recent advances in elucidating molecular pathways underlying adrenocortical carcinoma (ACC), this orphan malignancy is associated with poor survival. Identification of targetable genomic alterations is critical to improve outcomes. The objective of this study was to characterize the genomic profile of a large cohort of patient ACC samples to identify actionable genomic alterations. Three hundred sixty-four individual patient ACC tumors were analyzed. The median age of the cohort was 52 years and 60.9% (n = 222) were female. ACC samples had common alterations in epigenetic pathways with 38% of tumors carrying alterations in genes involved in histone modification, 21% in telomere lengthening, and 21% in SWI/SNF complex. Tumor suppressor genes and WNT signaling pathway were each mutated in 51% of tumors. Fifty (13.7%) ACC tumors had a genomic alteration in genes involved in the DNA mismatch repair (MMR) pathway with many tumors also displaying an unusually high number of mutations and a corresponding MMR mutation signature. In addition, genomic alterations in several genes not previously associated with ACC were observed, including IL7R, LRP1B, FRS2 mutated in 6, 8 and 4% of tumors, respectively. In total, 58.5% of ACC (n = 213) had at least one potentially actionable genomic alteration in 46 different genes. As more than half of ACC have one or more potentially actionable genomic alterations, this highlights the value of targeted sequencing for this orphan cancer with a poor prognosis. In addition, significant incidence of MMR gene alterations suggests that immunotherapy is a promising therapeutic for a considerable subset of ACC patients.


Raising the Working Temperature of a Triboelectric Nanogenerator by Quenching Down Electron Thermionic Emission in Contact-Electrification.
As previously demonstrated, contact-electrification (CE) is strongly dependent on temperature, however the highest temperature in which a triboelectric nanogenerator (TENG) can still function is unknown. Here, by designing and preparing a rotating free-standing mode Ti/SiO2 TENG, the relationship between CE and temperature is revealed. It is found that the dominant deterring factor of CE at high temperatures is the electron thermionic emission. Although it is normally difficult for CE to occur at temperatures higher than 583 K, the working temperature of the rotating TENG can be raised to 673 K when thermionic emission is prevented by direct physical contact of the two materials via preannealing. The surface states model is proposed for explaining the experimental phenomenon. Moreover, the developed electron cloud-potential well model accounts for the CE mechanism with temperature effects for all types of materials. The model indicates that besides thermionic emission of electrons, the atomic thermal vibration also influences CE. This study is fundamentally important for understanding triboelectrification, which will impact the design and improve the TENG for practical applications in a high temperature environment.


Lipoxin a4 analogs attenuate induction of intestinal epithelial proinflammatory gene expression and reduce the severity of dextran sodium sulfate-induced colitis.
The anti-inflammatory eicosanoid lipoxin A(4) (LXA(4)), aspirin-triggered 15-epi-LXA(4), and their stable analogs down-regulate IL-8 secretion and subsequent recruitment of neutrophils by intestinal epithelia. In an effort to elucidate the mechanism by which these lipid mediators modulate cellular proinflammatory programs, we surveyed global epithelial gene expression using cDNA microarrays. LXA(4) analog alone did not significantly affect expression of any of the >7000 genes analyzed. However, LXA(4) analog pretreatment attenuated induction of approximately 50% of the 125 genes up-regulated in response to the gastroenteritis-causing pathogen Salmonella typhimurium. A major subset of genes whose induction was reduced by LXA(4) analog pretreatment is regulated by NF-kappaB, suggesting that LXA(4) analog was influencing the activity of this transcription factor. Nanomolar concentrations of LXA(4) analog reduced NF-kappaB-mediated transcriptional activation in a LXA(4) receptor-dependent manner and inhibited induced degradation of IkappaBalpha. LXA(4) analog did not affect earlier stimulus-induced signaling events that lead to IkappaBalpha degradation, such as S. typhimurium-induced epithelial Ca(2+) mobilization or TNF-alpha-induced phosphorylation of IkappaBalpha. To establish the in vivo relevance of these findings, we examined whether LXA(4) analogs could affect intestinal inflammation in vivo using the mouse model of DSS-induced inflammatory colitis. Oral administration of LXA(4) analog (15-epi-16-para-fluoro-phenoxy-LXA(4), 10 microg/day) significantly reduced the weight loss, hematochezia, and mortality that characterize DSS colitis. Thus, LXA(4) analog-mediated down-regulation of proinflammatory gene expression via inhibition of the NF-kappaB pathway can be therapeutic for diseases characterized by mucosal inflammation.


The value of supply chain coordination under moral hazard: A case study of the consumer product supply chain.
In this paper, we examine a real-world case related to the consumer product supply chain to analyze the value of supply chain coordination under the condition of moral hazard. Because of the characteristics of a buyback contract scheme employed in the supply chain, the supplier company's sales department encourages retailers to order more inventory to meet their sales target, whereas retailers pay less attention to their inventory level and leftovers at the end of the season. This condition induces moral hazard problems in the operation of the supply chain, as suppliers suffer from huge returns of leftover inventory. This, in turn, is related to the obsolescence of returned inventory, even with penalty terms in the contract for the return of any leftovers. In this study, we show under the current buyback-based supply chain operation, the inventory levels of both the supplier and retailers exceed customer demand and develop vendor-managed inventory (VMI) system with base stock policy to remove any mismatch of supply and demand. A comparison of both systems shows that through the proper coordination of supply chain operations, both suppliers and retailers can gain additional benefits while providing proper services to end customers.


Measuring compassion toward others: Dimensionality of the compassion scale in community adolescents and in adolescents with behavioral disorders.
Compassion toward others has been defined as the sensitivity to the suffering of others with the genuine commitment to relieve/prevent it. The Compassion Scale (CS) measures this construct and despite its relevance during adolescence, studies have been mostly conducted with adults. This study investigated the psychometric properties of the Compassion Scale-Adolescents (CS-A) in community adolescents (n = 658; 409 girls) and in boys with behavioral disorders (n = 183), from 14 to 18 years old. Results showed the adequacy of a hierarchical-CFA measurement model, with a general score of compassion and four specific factors (i.e., Kindness, Common Humanity, Mindfulness and Indifference). Measurement invariance was tested across samples. Community girls presented higher levels of compassion when compared to boys. Also, behaviorally disturbed boys presented decreased levels of compassion when compared to community boys. Evidence for reliability and construct validity is also provided. The CS-A allows future research between genders in community adolescents. Additionally, future research exploring compassion using the CS-A, between community boys and samples of behaviorally disturbed boys, is now possible. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Coresidence of Older Parents and Adult Children Increases Older Adults' Self-Reported Psychological Well-Being.
A multigenerational household is no longer a rare phenomenon in contemporary society. However, relevant literature has focused on elderly parents receiving support from their adult child, thereby coresiding. This is potentially problematic, as both generations could benefit from living together, and little is known about the benefit of living with adult children from older adults' perspectives compared to the risk of this living situation. Previous research suggests a significant negative effect of living alone, e.g., low psychological well-being, and it becomes more salient among single parents, such as widowed or divorced. The current paper utilizes the National Health Measurement Study with a sample of age 55 and over. Their SF-36 Mental Health and Physical Health Component and self-acceptance scores were measured. Path analysis reveals that both physical and mental health and self-acceptance scores are lower among single older adults at the time of the survey (e.g., divorced and widowed) than among those who are nonsingle and living with their adult child. A complete mediation effect of living with an adult child on older adults' mental health and self-acceptance was observed in both White and non-White minority older adults. This suggests that living with an adult child possibly serves as a protective factor for the negative relationship between living alone and their well-being. The current study seeks to stimulate ideas that might generate the following answer to community-based care in our contemporary aging society.


The efficacy of DDAVP is related to the circadian rhythm of urine output in patients with persisting nocturnal enuresis.
Desmopressin may be a useful treatment in some, but not all, patients with nocturnal enuresis. We have evaluated a relation between nocturnal urine output in patients with primary monosymptomatic nocturnal enuresis and the treatment response to synthetic vasopressin. Adolescent or adult enuretics and normal subjects were enrolled in the study and admitted to hospital for a 24 hour investigation of the diurnal variation in urine output, plasma vasopressin (AVP) and plasma atrial natriuretic peptide (ANP). The enuretics were characterized prior to investigation as either 1-desamino-8-D-arginine vasopressin (DDAVP) responders or non-responders. During admission the fluid intake was restricted to 25 ml/kg per day. Twenty-four patients (15-37 years) with primary monosymptomatic nocturnal enuresis and 9 normal subjects (24-31 years). Circulating levels of AVP, ANP, plasma electrolytes and plasma osmolality were measured (1400, 2000, 2300, 0200, 0500 and 0800 hours) together with urine volume, urine osmolality and urine electrolytes during daytime and nighttime. Tubular reabsorptive capacity for water, osmoles and creatinine were assessed as well as urinary and fractional excretion rates of sodium and potassium. Controls and DDAVP non-responders had a significant decrease in urine output at night concomitant with a significant plasma AVP amplitude in peak/nadir values although both groups lacked a significant nocturnal increase in AVP. In contrast, in DDAVP responders there was no circadian variation in urine output and thus a nocturnal polyuria together with no oscillation in plasma AVP. The DDAVP responding group had a nocturnal urine production significantly larger than the two other groups. However, the mean 24 hour AVP levels were similar in all groups. The excessive urine production at night in DDAVP responders was accompanied by nocturnal natriuresis due to an increased fractional excretion of sodium. In contrast, nocturnal antidiuresis in controls and DDAVP non-responding enuretics coincided with diminished sodium excretion. Average ANP levels were elevated in both enuretic groups compared to normals, whereas a circadian variation was detected only in the latter. It is concluded that DDAVP responsiveness is linked to the nocturnal urine production and that no pathophysiological role can be ascribed to AVP or ANP in DDAVP refractory adolescent and adult enuretics. Moreover, it is suggested that an abnormal tubular handling of sodium may contribute to the nocturnal polyuria seen in DDAVP responders.


HHV8 a subtype is associated with rapidly evolving classic Kaposi's sarcoma.
The link between human herpesvirus 8 (KSHV) and Kaposi's sarcoma (KS) has been proven, but many important aspects including risk factors, genetic predisposition to tumor development, transmission of KSHV, and the pathogenic potential of different genotypes remain to be elucidated. Possible associations between clinical parameters and antibody levels, viral load fluctuations, and viral genotype were analyzed by quantitative real-time PCR, an in-house developed IFA assay, and sequence analysis of ORF K1-VR1 in blood, serum and saliva of 38 subjects with classic KS (cKS). KSHV lytic antibodies were significantly increased in stage IV compared to stage I and II patients (p = 0.006 and p = 0.041, respectively). KSHV blood, serum, and saliva viral load was comparable in all stages. The highest viral loads were detected in saliva, and they decreased in stages III-IV compared to stages I-II patients. Higher concentrations of lytic antibodies and higher viral loads were observed in fast progressing cKS patients, in whom KSHV detection from blood was also more frequent. Type A KSHV strain was almost exclusively present in rapid progressors (12/17 cases), while C type was mainly present in slow progressing patients (6/7 cases). Finally, detection of type A KSHV strain associated with higher blood viral loads. KSHV lytic antibody levels and viral load can be used to monitor clinical evolution of cKS. Infection supported by KSHV A subtype is associated with more rapid progressive disease. Careful monitoring and aggressive therapeutic protocols should be considered in patients with KSHV A-supported infection.


A light-triggerable formulation to control the stability of pro-angiogenic transcription factor hypoxia inducible factor-1α (HIF-1α).
The control of vascular remodeling mediated by transcription factor HIF-1α is critical in the treatment of several diseases including cancer, retinopathies, chronic wounds, and ischemic heart disease, among others. Gene silencing using a small interfering RNA (siRNA) is a promising therapeutic strategy to regulate HIF-1α; however, the delivery systems developed so far have limited endothelial targeting and efficiency. Herein, we have synthesized a light-triggerable polymeric nanoparticle (NP) library composed of 110 formulations which showed variable morphology, charge and disassembly rates after UV exposure. More than 35% of the formulations of the library were more efficient in gene knockdown than the siRNA delivered by a commercial transfection agent (lipofectamine RNAiMAX). The most efficient siRNA delivery formulations were tested against different cell types to identify one with preferential targeting to endothelial cells. Using a two-step methodology, we have identified a formulation that shows exquisite targeting to endothelial cells and is able to deliver more efficiently the siRNA that modulates HIF-1α than commercial transfection agents. Overall, the strategy reported here increases the specificity for tissue regulation and the efficiency for the intracellular delivery of siRNAs.


Growth modification treatment in class III malocclusions--an orthodontic case report.
A number of treatment options for Class III malocclusions have been reported. Early intervention incorporating growth modification allows the clinician to attempt mandibular growth restraint and promote the forward growth of the maxilla. At the optimal age for growth modification, rapid maxillary expansion (RME) and protraction headgear can be used to produce these beneficial changes. The following case report describes the management of an 8.5-year-old patient who underwent treatment using RME, protraction headgear and fixed appliances.


Genetically determined resistance to lethal murine cytomegalovirus infection is mediated by interferon-dependent and -independent restriction of virus replication.
Susceptibility of 4-week-old mice of different strains to lethal murine cytomegalovirus (MCMV) infection was studied. Strains homozygous for H-2k and C57BL strains were resistant to greater than or equal to 10(5.5) PFU. B10.BR mice congenic for C57BL background genes and H-2k were about 10-fold more resistant than either C3H/HeN or C57BL strains. BALB/c mice (H-2d) were susceptible (50% lethal dose, 10(5.05) PFU). This susceptibility was dominant over resistance associated with H-2k but not that associated with C57BL background genes. The dominant susceptibility trait segregated in backcross mice as if carried by a single gene. Virus replication in spleen cells in vivo correlated with susceptibility to lethal infection. A similar trend was found in tests of salivary glands. Replication of MCMV in vitro in cultures of adherent spleen cells and primary mouse embryo cells correlated with replication in vivo. Neutralization of interferon (IFN) in cultures of adherent spleen cells reversed H-2k-linked restriction of viral replication but had minor effects on cells of other strains. Natural killer cell responses to infection were often higher in more resistant strains, but B10.BR mice developed minimal natural killer cell responses. Specific antibody and cytotoxic T cell responses in B10.BR mice were similar or lower than in other strains. Thus, resistance to lethal MCMV infection was not immunologically mediated, was dependent on and reflected by the capacity of cells from a given mouse strain to support replication in vivo and in vitro, and was IFN dependent and recessive if linked to H-2k but IFN independent when associated with C57BL background genes.


Creating a culture of patient safety in a primary-care physician group.
Typically risk-management strategies have been applied to the inpatient setting. In 2003, a comprehensive risk-management program was introduced to ProHealth Physicians, one of the largest primary-care practice groups in Connecticut. The program included strategies for education, practice change, incentive and compliance. Performance metrics for clinician participation and compliance were prespecified. Clinicians' attitudes and behavior change were assessed after introduction of the program. Audits were conducted by external reviewers to assess compliance. Financial data from before-to-after program implementation were compared. Results showed fewer claims and substantial cost savings. A strong commitment to the implementation of a comprehensive risk-management program can create a culture of safety in an outpatient setting.