Experimental scrambling and noise reduction applied to the optical encryption of QR codes.
In this contribution, we implement two techniques to reinforce optical encryption, which we restrict in particular to the QR codes, but could be applied in a general encoding situation. To our knowledge, we present the first experimental-positional optical scrambling merged with an optical encryption procedure. The inclusion of an experimental scrambling technique in an optical encryption protocol, in particular dealing with a QR code "container", adds more protection to the encoding proposal. Additionally, a nonlinear normalization technique is applied to reduce the noise over the recovered images besides increasing the security against attacks. The opto-digital techniques employ an interferometric arrangement and a joint transform correlator encrypting architecture. The experimental results demonstrate the capability of the methods to accomplish the task.


The geochemical behavior of aluminum in acidified surface waters.
Speciation calculations for aluminum, in water samples taken from a drainage basin containing acid mine waters, demonstrate a distinct transition from conservative behavior for pH below 4.6 to nonconservative behavior for pH above 4.9. This transition corresponds to the pK for the first hydrolysis constant of the aqueous aluminum ion and appears to be a consistent phenomenon independent of field location, ionic strength, and sulfate concentration. Nonconservative behavior is closely correlated with the equilibrium solubility of a microcrystalline gibbsite or amorphous aluminum hydroxide.


Spatial filtering for noise reduction in a multirecording telecine system.
The purpose is to determine the transfer function of the two-dimensional Wiener filter in a color telecine system using multirecorded monochrome photographic film in which three-color information of an object is recorded separately with different spatial frequency regions. According to theory, the S/N of a high frequency carrier signal is improved approximately 10 dB with the Wiener filter, A Wiener filter is produced by introducing a coherent spatial filtering optical system into the telecine system. Satisfactory results were obtained in the filtering experiments on actual production of the Wiener filter.


Coding sequence of the overexpressed transcript of the putative oncogene PRAD1/cyclin D1 in two primary human tumors.
PRAD1 (cyclin D1) is a recently identified member of the family of cyclin genes, believed to play roles in regulating transitions through the cell cycle. The PRAD1 gene, located at 11q13, has been implicated in the pathogenesis of a variety of tumors, including parathyroid adenomas, t(11;14) bearing B-lymphoid tumors (particularly centrocytic lymphomas) where it is highly likely to be the BCL1 oncogene, and possibly in breast carcinomas and squamous cell cancers of the head and neck as well. PRAD1's tumorigenic influence appears to be effected through overexpression of its normal-sized transcript, but it has not been established whether the transcript's coding sequence is normal or contains oncogenic mutations. We have sequenced the coding region of the overexpressed PRAD1 transcript from two primary tumors with clonal PRAD1 region rearrangements: a benign parathyroid adenoma and a malignant centrocytic lymphoma. Each sequence is identical to the normal PRAD1 cDNA sequence, and presumably encodes normal PRAD1 protein. Thus, PRAD1 likely functions as a direct-acting oncogene whose rearrangement in tumors leads to overexpression or deregulated expression of its normal protein product.


Waist-to-hip ratio, dyslipidemia, glycemic levels, blood pressure and depressive symptoms among diabetic and non-diabetic Chinese women: a cross-sectional study.
To explore the relationship between depressive symptoms and waist-to-hip ratio, dyslipidemia, glycemic levels or blood pressure among diabetic and non-diabetic Chinese women. 11,908 women aged ≥40 years were enrolled in this cross-sectional study, including 2,511 with type 2 diabetes and 9,397 without. Depressive symptoms (defined as having mild-to-severe depressive symptoms) were assessed by the Patient Health Questionnaire-9 (PHQ-9) diagnostic algorithm. The prevalence and the odds ratios (ORs) with 95% confidence intervals (CIs) for having depressive symptoms were estimated using logistic regression analysis. The age-adjusted prevalence of depressive symptoms was significantly higher in non-diabetic subjects with waist-to-hip ratio (WHR) ≥0.9 (8.6%, age-adjusted OR 1.51 [95% CI 1.17, 1.95]), total cholesterol (TC)>6.22 mmol/L (8.8%, 1.58 [1.16, 2.15]), and Hemoglobin A1c (HbA1c) ≥6.00 mmol/L (7.7%, 1.69 [1.34, 2.14]), while it was significantly lower in non-diabetic subjects with diastolic blood pressure (DBP) between 80 to 89 mmHg (6.2%, 0.78 [0.64, 0.95]). These relationships remained significant even after controlling for multiple factors (WHR ≥0.9: multivariable-adjusted OR 1.39 [95% CI 1.07, 1.80]; TC>6.22 mmol/L: 1.56 [1.14, 2.12]; HbA1c ≥6.00 mmol/L: 1.64 [1.30, 2.08]; DBP 80-89 mmHg: 0.78 [0.64, 0.95]). However, no significant trend between depressive symptoms and WHC, TC, HbA1c, DBP was observed in diabetic women, and no significant trend relationship between depressive symptoms and BMI, WC, TG, or SBP was observed in both non-diabetic and diabetic women. Moreover, the prevalence of depressive symptoms was significantly higher in previously-diagnosed diabetes, compared with non-diabetic subjects, while no significant differences were observed between newly-diagnosed diabetes and non-diabetic subjects. The present study showed a relationship between WHR, TC, HbA1c, DBP and depressive symptoms among non-diabetic women, while no significant relationship between them was observed among diabetic women, even after controlling for multiple confounding factors.


Right cerebral hemispheric sensitivity to pH and physiological ions in fixed post-mortem Wistar rat brains.
Post-mortem human neural tissues fixed in ethanol and aldehyde-based solutions express modulated frequency-dependent microvolt potentials when probed by chemical and electrical stimuli. These observations run contrary to the assumption that basic tissue functions are irreversibly impaired upon fixation, in the absence of nutrients and sufficient concentrations of physiological ions. The aim of the current study was to investigate the relative effects of pH and specific charged particles relevant to normal cell physiology upon electric potentials associated with fixed post-mortem rat brain tissue. We identified a positive relationship between the total time the brains had been immersed in ethanol-formalin-acetic acid and high-frequency microvolt potentials within the dorsal right hemisphere of the rat cerebrum. Measuring the pH of the fixative solution surrounding the brains indicated that as time increased, a logarithmic trend toward alkalinity could be observed. Further experiments revealed that high-frequency microvolt potentials were related to pH changes within the right hemisphere only. The right ventral cerebrum displayed a unique response to potassium chloride in ways uncounted for by pH alone. The results suggest that the fixed post-mortem right cerebrum of the rat is particularly sensitive to pH and physiological ions which explains a subset of previous findings with respect to stimulus-response patterns in human coronal brain sections. A concluding hypothesis is presented which suggests that brain tissue expresses material properties independent of metabolic activity though perhaps relevant to living brain function.


[Teaching laparoscopic urologic oncology. The Memorial Sloan-Kettering Cancer Center experience].
We outline the structure of the clinical and training program of laparoscopic urologic oncology at Memorial Sloan-Kettering Cancer Center. We discuss the steps and key elements necessary in acquiring lapa roscopic proficiency. The program lasts 2 years and trains fellows and faculty. For fellows, the program consists of a 6 months high volume laparoscopic oncology rotation, during which dry lab, animal lab, vide review and operating room experience are required. For faculty, the program consists of 1 accredited continuin medical education course, 20 hours of dry lab, 1 session animal lab, observation of laparoscopic cases, first assistant in a minimum of 15 laparoscopic cases, performing laparoscopic cases under mentoring. 8 fellows have completed the training, 4 of whom have completed their fellowship and are in academic centers, performing advanced laparoscopy. The laparoscopic approach represents on average 80% of their urologic practice. Three attendings are performing laparoscopic surgery with mentoring. The goals of a surgical education program should be the standardization of the acquisition o surgical skills and assessment of the performance in a uniform setting to ensure the maintenance of the acquisition of skills and to develop programs to teach new skills.


Fluoxetine for migraine prophylaxis: a double-blind trial.
Selective serotonin reuptake inhibitors have recently been used in the treatment of migraine. We studied the safety and efficacy of fluoxetine in the prevention of migraine. Between February 1997 and December 1997, we examined 52 patients (33 women) at the Headache Diagnosis and Therapy Service of the Second University of Naples. Ages ranged from 18 to 65 years, and all patients suffered from migraine without aura according to IHS 1988 criteria. The sample was divided into two groups: group A included 32 patients (19 women; mean age, 36.8 years [SD 12.4]) who received fluoxetine at a dosage of 20 mg per day; group B included 20 patients (14 women; mean age, 38.8 years [SD 15.6]) who received placebo. Our study was a single-center, randomized, double-blind, parallel study of fluoxetine for the prophylactic control of migraine and consisted of two phases: 30 days of pharmacological wash out and 6 months of therapy with monthly follow-up. Patients were randomly assigned to two groups: A, fluoxetine or B, placebo. At the first visit, patients provided a detailed history and underwent neurological evaluation and a Zung test for depression. No pathological values were revealed. In order to monitor symptomatology, all patients received a form for the calculation of the total pain index at monthly follow-up. A comparison of the total pain index between basal values (calculated during the period of wash out) and monthly follow-up (calculated monthly during the period of 6 months of the therapy) showed significant reduction (P < .05) beginning from the third month of treatment in the fluoxetine group and no significant reduction in the placebo group. Even if preliminary and to be confirmed, these data seem to support the use of fluoxetine in the treatment of migraine.


Polyhedral microcalcifications at mammography: histologic correlation with calcium oxalate.
Pathologists have associated calcium oxalate dihydrate (weddellite) in breast biopsy specimens with benign or borderline lesions and rarely with malignancy. These microcalcifications may have a polyhedral shape in histologic specimens owing to their crystalline structure. A retrospective radiologic-histologic correlation study was performed on 300 clusters of microcalcifications to determine if microcalcifications with a polyhedral shape could be found at mammography. In 19 cases (6.3%), polyhedral microcalcifications (PMs) were detected by two radiologists. In 12 of these 19 cases, weddellite crystals were found in the histologic specimen under polarized light; in seven cases, no calcification was found. Although rare, PMs can be found at mammography by radiologists aware of their existence. They are due to weddellite crystals and in this series were associated with benign disease in 89% of cases. Prospective studies are required to determine the frequency of PMs on screening mammograms and to evaluate their negative predictive value.


Angiographic treatment of gastrointestinal hemorrhage: comparison of vasopressin infusion and embolization.
The results of selective intraarterial vasopressin-infusion therapy and embolization therapy were compared in two groups of patients with major gastrointestinal hemorrhage. The site of bleeding, clinical course, complications, and transfusion requirements were evaluated in each group. Intraarterial vasopressin infusion therapy resulted in successful control of hemorrhage in 16 (70%) of 23 patients. Four patients, however, rebled and an operation was necessary, reducing the overall success rate to 52% (12 of 23). In the group treated with embolization therapy, primary success was achieved in 17 (71%) of 24 patients. Four patients in whom initial embolization failed to control bleeding underwent repeat embolization and in all four permanent control of hemorrhage was obtained, producing an overall success rate of 21 (88%) of 24. Analysis of our results according to site of hemorrhage suggests that at certain sites embolization is a preferred method of treatment; embolization allows earlier control of gastrointestinal hemorrhage and a reduction in transfusion requirements.


Patient characteristics and healthcare utilisation among Danish patients with chronic conditions: a nationwide cohort study in general practice and hospitals.
The complexity of caring for patients with chronic conditions necessitates new models of integrated care to accommodate an increasing demand. To inform the development of integrated care models, it is essential to map patients' use of healthcare resources. In this nationwide registry-based cohort study, we describe and compare patient characteristics and healthcare utilisation between Danish patients with chronic conditions in general practice follow-up and in hospital outpatient follow-up. On 1 January 2016, we identified 250,402 patients registered in 2006-2015 with a hospital diagnosis of atrial fibrillation/flutter, congestive heart failure, chronic liver disease, inflammatory bowel disease or chronic obstructive pulmonary disease. By linkage to national social and health registries, patient characteristics and 12-month healthcare utilisation were extracted. Incidence rates of health care utilisation were compared between patients with chronic conditions in general practice follow-up and patients in hospital outpatient follow-up using negative binomial regression. Across all five conditions, the largest proportions of patients were in general practice follow-up (range = 59-87%). Patients in hospital outpatient follow-up had higher rates of exacerbation-related admissions (adjusted incidence rate ratio (IRR) range = 1.3 to 2.8) and total length of stay (IRR range = 1.2 to 2.2). For these five conditions, all-cause admissions and lengths of stay, general practice daytime and out-of-hours contacts, and municipal home nursing contacts were similar between follow-up groups or higher among patients in general practice follow-up. The exception was patients with chronic obstructive pulmonary disease, where patients in hospital outpatient follow-up had higher utilisation of healthcare resources. Patients in general practice follow-up accounted for the largest proportion of total healthcare utilisation, but patients in hospital outpatient follow-up were characterised by high exacerbation rates. Enhanced integration of chronic care may be of most benefit if patients in general practice follow-up are targeted, but it is also likely to have an impact on exacerbation rates among patients in hospital outpatient follow-up.


In vivo efficacy of trovafloxacin (CP-99,219), a new quinolone with extended activities against gram-positive pathogens, Streptococcus pneumoniae, and Bacteroides fragilis.
The interesting in vitro antimicrobial activity and pharmacokinetics of the new quinolone trovafloxacin (CP-99,219) warranted further studies to determine its in vivo efficacy in models of infectious disease. The significance of the pharmacokinetic and in vitro antimicrobial profiles of trovafloxacin was shown through efficacy in a series of animal infection models by employing primarily oral therapy. Against acute infections, trovafloxacin was consistently more effective than temafloxacin, ciprofloxacin, and ofloxacin against Streptococcus pneumoniae and other gram-positive pathogens while maintaining activity comparable to that of ciprofloxacin against gram-negative organisms. In a model of murine pneumonia, trovafloxacin was more efficacious than temafloxacin, while ciprofloxacin failed against S. pneumoniae (50% protective doses, 2.1, 29.5, and >100 mg/kg, respectively). In addition to its inherent in vitro potency advantage against S. pneumoniae, these data were supported by a pharmacokinetic study that showed levels of trovafloxacin in pulmonary tissue of S. pneumoniae-infected CF1 mice to be considerably greater than those of temafloxacin and ciprofloxacin (twice the maximum drug concentration in serum; two to three times the half-life, and three to six times the area under the concentration-time curve). Against localized mixed anaerobic infections, trovafloxacin was the only agent to effectively reduce the numbers of recoverable CFU of Bacteroides fragilis ( >1,000-fold), Staphylococcus aureus (1,000-fold), and Escherichia coli ( >100-fold) compared with ciprofloxacin, vancomycin, metronidazole, clindamycin, cefoxitin, and ceftriaxone. The in vitro and in vivo antimicrobial activities of trovafloxacin and its pharmacokinetics in laboratory animals provide support for the ongoing and planned human phase II and III clinical trials.


The Azolla, Anabaena azollae Relationship: I. Initial Characterization of the Association.
Cultures of Azolla caroliniana Willd. free of the symbiotic blue-green alga, Anabaena azollae, were obtained by treatment of Azolla fronds with a regimen of antibiotics. These symbiontfree plants can be maintained only on medium containing a combined nitrogen source.Morphological aspects of the symbiotic association show the confinement of the Anabaena azollae within the leaf cavity of the Azolla. Procedures were established for the isolation of pure preparations of Anabaena azollae and Azolla chloroplasts. It has not yet been possible to grow the isolated alga in independent culture.Photochemical activities of the isolated alga and fern chloroplasts were measured by spectrophotometric assays for photosystems I and II as well as by P700-content (photosystem I) and delayed light emission (photosystem II). In the algal fraction, both photosystems were repressed when compared to freeliving Anabaena cylindrica, but the relative ratio of photosystem I to photosystem II may be appreciably greater in Anabaena azollae. Azolla chloroplasts were generally comparable to spinach chloroplasts.A comparison of the chlorophyll a and b content of Azolla fronds with and without the symbiotic alga resulted in an estimate that in the symbiotic association, the Anabaena azollae accounts for from 7.5 to 15% of the total chlorophyll.


Parallel cholesterol crystals: a sign of impending plaque rupture?
Currently, there are no available methods that can reliably predict when or if an atheroma will rupture. Recent reports suggest cholesterol crystals (CCs), present within the necrotic core, are sharp and can penetrate and disrupt the fibrous cap, contributing to plaque rupture. Our aim is to show CC, normally distributed at random within the necrotic core, often develop a parallel configuration at the site of plaque disruption (PD) which may be a sign of impending plaque rupture. The coronary arteries of 83 patients who died of acute coronary disease (ACD) were injected with a colored barium gelatin mass. The arteries were dissected, decalcified, cut at 2-3 mm intervals, and all segments mounted for microscopic study. All segments were reviewed to identify PDs and to determine the frequency of parallel cholesterol crystals (P-CCs) at the site of these PDs. There were 215 separate PDs in 83 patients, with 64 (77%) patients showing more than one PD. P-CCs were present in 126 (59%) of all PDs regardless of plaque size or the severity of luminal stenosis and were present with or without luminal thrombosis. Luminal thrombosis was present in 105 PDs (49%), primarily in those segments showing significant luminal stenosis. There was no significant difference in the frequency of luminal thrombosis in those PDs with or without P-CCs. P-CCs are commonly present at the site of PD and may contribute to PD by penetrating and disrupting the fibrous cap. The ability to recognize this parallel configuration may help to identify plaques with impending plaque rupture.


The impact of the demographic shift on limb amputation incidence in Saskatchewan, Canada, 2006-2019.
Changing demographics in a population may have an inevitable influence on disease incidence including limb amputation. However, the extent to which these changes affect limb amputation (LA) is unknown. Understanding the impact of changing demographics on LA would provide the best opportunity to plan for the future. We assessed the impact of changes in age and sex on limb amputation in Saskatchewan between 2006 and 2019. Retrospective linked Saskatchewan's LA cases, and demographic characteristics and residents population from 2006-2019 was used. The amputation rate was calculated by dividing the total number of LA cases recorded each year by the annual Saskatchewan resident population and the results expressed per 100,000 populations. Furthermore, decomposition analysis was used to assess the impact of changes in age and sex on LA in a decade (2008-2017) and the Generalized Additive Model (GAM) was employed to examine the linear and non-linear effect of age. We found that in the ten years (2008-2017), the absolute LA rate difference was 9.0 per 100,000 population. Changes in age structure alone contributed 7.7% to the LA rate increase and 92.3% to changes in age-specific LA rates. The decade witnessed a marginal population difference between males and females, but the LA rate was 2.1-2.2 times higher in males than in females. The GAM revealed a non-linear relationship between LA and age, and further indicates that the risk of LA significantly increased as age increases. In a decade, we found that changes in age distribution and age-specific rate substantially impacted the increase in the LA rate observed in the province. This highlights the urgent need for strategized programs to respond to these changes as both the population and diabetes, which is age-dependent and a leading cause of LA, are expected to increase in the province by 2030. As changes in population and demographic factors are inevitable, this study provides data for policy makers on the need for continuous incorporation of the shift in population in the design of future health services.


Gene Editing Correction of a Urea Cycle Defect in Organoid Stem Cell Derived Hepatocyte-like Cells.
Urea cycle disorders are enzymopathies resulting from inherited deficiencies in any genes of the cycle. In severe cases, currently available therapies are marginally effective, with liver transplantation being the only definitive treatment. Donor liver availability can limit even this therapy. Identification of novel therapeutics for genetic-based liver diseases requires models that provide measurable hepatic functions and phenotypes. Advances in stem cell and genome editing technologies could provide models for the investigation of cell-based genetic diseases, as well as the platforms for drug discovery. This report demonstrates a practical, and widely applicable, approach that includes the successful reprogramming of somatic cells from a patient with a urea cycle defect, their genetic correction and differentiation into hepatic organoids, and the subsequent demonstration of genetic and phenotypic change in the edited cells consistent with the correction of the defect. While individually rare, there is a large number of other genetic-based liver diseases. The approach described here could be applied to a broad range and a large number of patients with these hepatic diseases where it could serve as an in vitro model, as well as identify successful strategies for corrective cell-based therapy.


Clinical outcomes of del nido cardioplegia and st thomas blood cardioplegia in neonatal congenital heart surgery.
Cardioplegia is essential for adequate myocardial protection. There continues to remain ambiguity regarding the ideal cardioplegia for adequate myocardial protection in congenital heart surgery. This study compares clinical outcomes using St Thomas II solution and Del Nido cardioplegia in neonates undergoing cardiac surgery. All neonates (<30 days) from 2011 to 2017 who underwent surgery requiring cardioplegic arrest were analyzed retrospectively. We divided the cohort into two groups depending on cardioplegia received, as group A (Blood cardioplegia with St Thomas II solution, n = 56) and group B (Del Nido cardioplegia, n = 48). Various demographic, intraoperative, early postoperative, and discharge variables were analyzed. Two groups were similar in age, gender, pre-operative diagnosis, and risk category. Cardiopulmonary bypass (CPB) time (P = 0.002), aortic cross-clamp (ACC) time (P = 0.018), and the number of doses of cardioplegia (P < 0.001) were significantly lower with Del Nido group. Though vasoactive inotropic score (VIS) (P = 0.036) was high during the first 24 h in the immediate postoperative period in group A, there was no difference in early mortality among both groups (P = 0.749). Both groups did not show significant differences related to various postoperative and discharge variables. When compared to St. Thomas solution, the use of Del Nido cardioplegia solution in neonates is associated with a significant decrease in CPB and ACC times and VIS in the first 24 h after surgery. The choice of cardioplegia (St Thomas/Del Nido) in neonates does not affect early mortality and early postoperative clinical outcomes.


New concepts in sepsis.
An estimated 750,000 cases of severe sepsis occur annually in the United States, and the mortality rate is about 30%. As a condition that disproportionately affects the elderly and is related to invasive and immunosuppressive healthcare, increases in the frequency of sepsis are anticipated. The complex pathophysiology of sepsis encompasses the interplay of pro- and anti-inflammatory mediators, activated circulating and resident inflammatory cells, disrupted coagulation, endothelial activation and injury, vasodilatation and vascular hyporesponsiveness to vasoactive mediators, cardiac dysfunction, and cellular dysoxia. Current management of severe sepsis includes eradication of infection through source control and antimicrobial therapy, aggressive and targeted shock resuscitation that includes fluid administration, correction of anemia, vasopressor support, modest inotropic therapy, infusion of human recombinant activated protein C to selected patients, and compulsive supportive care to manage organ dysfunction and to avoid complications.


The use of esmarch exsanguination for the treatment of extremity wound burns.
Tourniquets are routinely used during the excising and grafting of burn wounds located on the limbs in order to decrease blood loss. It has been postulated that the exsanguination of extremities by using Esmarch bandages might further reduce blood loss. However, there are concerns about a decrease in graft quality when Esmarch bandages are applied. The purpose of this prospective, double-blinded randomized study was to compare Esmarch application in addition to tourniquet (exsanguinated extremities) with the application of tourniquet alone. Thirty-eight excisions of bilateral extremity wounds were performed. Both limbs were tangentially excised after tourniquet application with one limb randomly chosen for prior Esmarch exsanguination. Blood loss was estimated during this procedure. Graft take was assessed twice: on post-operative days 3 and 7. The burn surface area and total area grafted were equivalent in the extremities with Esmarch bandages when compared to the extremities without them. Total blood loss was less in the extremities where Esmarch was applied. Graft take was similar in the two groups. Statistical analysis was performed with a two-tailed paired T-test. It is concluded that the use of Esmarch exsanguination in addition to tourniquet further reduces blood loss without affecting the quality of the engraftment.


Analysis of Drosophila lipids by matrix-assisted laser desorption/ionization mass spectrometric imaging.
Drosophila melanogaster is a major model organism for numerous lipid-related diseases. While comprehensive lipidomic profiles have been generated for D. melanogaster, little information is available on the localization of individual lipid classes and species. Here, we show the use of matrix-assisted laser desorption/ionization mass spectrometric imaging (MALDI-MSI) to profile lipids in D. melanogaster tissue sections. The preparation of intact cryosections from whole insects presents a challenge due to the brittle hydrophobic cuticle surrounding the body and heterogeneous tissue types beneath the cuticle. However, the introduction of a novel sucrose infiltration step and gelatin as an embedding media greatly improved the quality of tissue sections. We generated MS image profiles of six major lipid classes: phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol, phosphatidylserine, and triacylglycerides. In addition, signals corresponding to two male-specific sex pheromones were detected in the ejaculatory bulb, a specialized site of pheromone production. MSI performed with 35 μm lateral resolution provided high sensitivity detection of at least 92 different lipid species, based on exact mass. In contrast, MSI with 10 μm lateral resolution enabled the detection of 36 lipid species but allowed lipid profiling of individual organs. The ability to localize lipid classes in intact sections from whole Drosophila provides a powerful tool for characterizing the effects of diet, age, stress, and environment on lipid production and distribution.


Clp and Lon proteases occupy distinct subcellular positions in Bacillus subtilis.
Among other functions, ATP-dependent proteases degrade misfolded proteins and remove several key regulatory proteins necessary to activate stress responses. In Bacillus subtilis, ClpX, ClpE, and ClpC form homohexameric ATPases that couple to the ClpP peptidase. To understand where these peptidases and ATPases localize in living cells, each protein was fused to a fluorescent moiety. We found that ClpX-GFP (green fluorescent protein) and ClpP-GFP localized as focal assemblies in areas that were not occupied by the nucleoid. We found that the percentage of cells with ClpP-GFP foci increased following heat shock independently of protein synthesis. We determined that ClpE-YFP (yellow fluorescent protein) and ClpC-YFP formed foci coincident with nucleoid edges, usually near cell poles. Furthermore, we found that ClpQ-YFP (HslV) localized as small foci, usually positioned near the cell membrane. We found that ClpQ-YFP foci were dependent on the presence of the cognate hexameric ATPase ClpY (HslU). Moreover, we found that LonA-GFP is coincident with the nucleoid during normal growth and that LonA-GFP also localized to the forespore during development. We also investigated LonB-GFP and found that this protein localized to the forespore membrane early in development, followed by localization throughout the forespore later in development. Our comprehensive study has shown that in B. subtilis several ATP-fueled proteases occupy distinct subcellular locations. With these data, we suggest that substrate specificity could be determined, in part, by the spatial and temporal organization of proteases in vivo.


'They won't change it back in their heads that we're trash': the intersection of sex work-related stigma and evolving policing strategies.
In Vancouver, Canada, there has been a continuous shift in the policing of sex work away from arresting sex workers, which led to the implementation of a policing strategy that explicitly prioritised the safety of sex workers and continued to target sex workers' clients. We conducted semi-structured interviews with 26 cisgender and five transgender women street-based sex workers about their working conditions. Data were analysed thematically and by drawing on concepts of structural stigma and vulnerability. Our results indicated that despite police rhetoric of prioritising the safety of sex workers, participants were denied their citizenship rights for police protection by virtue of their 'risky' occupation and were thus responsiblised for sex work related violence. Our findings further suggest that sex workers' interactions with neighbourhood residents were predominantly shaped by a discourse of sex workers as a 'risky' presence in the urban landscape and police took swift action in removing sex workers in the case of complaints. This study highlights that intersecting regimes of stigmatisation and criminalisation continued to undermine sex workers citizenship rights to police protection and legal recourse and perpetuated labour conditions that render sex workers at increased risk for violence and poor health.


Investigation into the sequence structure of 23 Y chromosomal STR loci using massively parallel sequencing.
Next-generation sequencing (NGS) can produce massively parallel sequencing (MPS) data for many targeted regions with a high depth of coverage, suggesting its successful application to the amplicons of forensic genetic markers. In the present study, we evaluated the practical utility of MPS in Y-chromosome short tandem repeat (Y-STR) analysis using a multiplex polymerase chain reaction (PCR) system. The multiplex PCR system simultaneously amplified 24 Y-chromosomal markers, including the PowerPlex® Y23 loci (DYS19, DYS385ab, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS481, DYS533, DYS549, DYS570, DYS576, DYS635, DYS643, and YGATAH4) and the M175 marker with the small-sized amplicons ranging from 85 to 253bp. The barcoded libraries for the amplicons of the 24 Y-chromosomal markers were produced using a simplified PCR-based library preparation method and successfully sequenced using MPS on a MiSeq® System with samples from 250 unrelated Korean males. The genotyping concordance between MPS and the capillary electrophoresis (CE) method, as well as the sequence structure of the 23 Y-STRs, were investigated. Three samples exhibited discordance between the MPS and CE results at DYS385, DYS439, and DYS576. There were 12 Y-STR loci that showed sequence variations in the alleles by a fragment size determination, and the most varied alleles occurred in DYS389II with a different sequence structure in the repeat region. The largest increase in gene diversity between the CE and MPS results was in DYS437 at +34.41%. Single nucleotide polymorphisms (SNPs), insertions, and deletions (indels) were observed in the flanking regions of DYS481, DYS576, and DYS385, respectively. Stutter and noise ratios of the 23 Y-STRs using the developed MPS system were also investigated. Based on these results, the MPS analysis system used in this study could facilitate the investigation into the sequences of the 23 Y-STRs in forensic genetics laboratories.


Elbow dislocation during overhead skeletal traction therapy: a case report.
A dislocation of the elbow occurred in a 7-year-old boy during overhead skeletal traction treatment for a supracondylar fracture of the humerus. Closed reduction of the dislocation was successful. A review of the literature failed to reveal a report of a similar incident.


Venetoclax or placebo in combination with bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma (BELLINI): a randomised, double-blind, multicentre, phase 3 trial.
Venetoclax is a highly selective, potent, oral BCL-2 inhibitor, which induces apoptosis in multiple myeloma cells. Venetoclax plus bortezomib and dexamethasone has shown encouraging clinical efficacy with acceptable safety and tolerability in a phase 1 trial. The aim of this study was to evaluate venetoclax plus bortezomib and dexamethasone in patients with relapsed or refractory multiple myeloma. In this randomised, double-blind, multicentre, phase 3 trial, patients aged 18 years or older with relapsed or refractory multiple myeloma, an Eastern Cooperative Oncology Group performance status of 2 or less, who had received one to three previous therapies were enrolled from 90 hospitals in 16 countries. Eligible patients were randomly assigned (2:1) centrally using an interactive response technology system and a block size of three to receive venetoclax (800 mg per day orally) or placebo with bortezomib (1·3 mg/m2 subcutaneously or intravenously and dexamethasone (20 mg orally). Treatment was given in 21-day cycles for the first eight cycles and 35-day cycles from the ninth cycle until disease progression, unacceptable toxicity, or patient withdrawal. Randomisation was stratified by previous exposure to a proteasome inhibitor and the number of previous therapies. Sponsors, investigators, study site personnel, and patients were masked to the treatment allocation throughout the study. The primary endpoint was independent review committee-assessed progression-free survival in the intention-to-treat population. Safety analyses were done in patients who received at least one dose of study drug. This study is registered with ClinicalTrials.gov, NCT02755597. Between July 19, 2016, and Oct 31, 2017, 291 patients were randomly assigned to receive venetoclax (n=194) or placebo (n=97). With a median follow-up of 18·7 months (IQR 16·6-21·0), median progression-free survival according to independent review committee was 22·4 months (95% CI 15·3-not estimable) with venetoclax versus 11·5 months (9·6-15·0) with placebo (hazard ratio [HR] 0·63 [95% CI 0·44-0·90]; p=0·010). The most common grade 3 or worse treatment-emergent adverse events were neutropenia (35 [18%] of 193 patients in the venetoclax group vs seven [7%] of 96 patients in the placebo group), pneumonia (30 [16%] vs nine [9%]), thrombocytopenia (28 [15%] vs 29 [30%]), anaemia (28 [15%] vs 14 [15%]), and diarrhoea (28 [15%] vs 11 [11%]). Serious treatment-emergent adverse events occurred in 93 (48%) patients in the venetoclax group and 48 (50%) patients in the placebo group, with eight (4%) treatment-emergent fatal infections reported in the venetoclax group and none reported in the placebo group. Three deaths in the venetoclax group (two from pneumonia and one from septic shock) were considered treatment-related; no deaths in the placebo group were treatment-related. The primary endpoint was met with a significant improvement in independent review committee-assessed progression-free survival with venetoclax versus placebo plus bortezomib and dexamethasone. However, increased mortality was seen in the venetoclax group, mostly because of an increased rate of infections, highlighting the importance of appropriate selection of patients for this treatment option. AbbVie and Genentech.


Toward a social psychology of program design.
Underlying each aspect of the design of social programs, whether the fund-raising apparatus or the accountability system, is a conception of human behavior. These conceptions, generally implied, are seldom examined, yet their validity determines to a great extent the effectiveness of programs. We have lacked an operational means of translating our behavioral assumptions about clients, staff, organizations, and groups into concepts whereby the merits and deficits of various designs can be evaluated. Viewing social programs and policies as forms of exchange where resources are invested for potential benefits offers a promising bridge between behavior and design.


Adaptive pathology: new insights into the physical examination and imaging of the thrower's shoulder and elbow.
Throwing with high velocity requires extremes of glenohumeral external rotation of the abducted arm where particularly high forces in the shoulder and elbow are endured. Repeated throwing leads to dominant-arm bony remodeling of the humerus, glenoid, and elbow, and multiple soft tissue changes that would be considered abnormal. Many of these features are thought to be adaptive and protective. The purpose of this work is to (1) define the concept of adaptive pathology; (2) review the mechanics of the throwing motion; (3) review pertinent physical examination and imaging findings seen in asymptomatic throwers' shoulders and elbows and describe how these changes develop and may be adaptive-allowing the thrower to perform at high levels; and then (4) review the principles of surgical treatment in the throwing athletes, which should focus on reducing symptoms, but not necessarily restoring the thrower's anatomy to normal.


Networks with lateral connectivity. I. dynamic properties mediated by the balance of intrinsic excitation and inhibition.
1. We studied the rapid dynamic changes of neuron response properties in the somatosensory cortex by the use of computer simulations. The model consists of three feedforward layers of spiking neurons, corresponding to skin, subcortex, and cortex structures. Measurements and analysis of model activity throughout this work are similar to those used in neurophysiological experiments. 2. The effects of various parameters on response properties of model neurons were investigated. The most important parameters were the lateral excitation and inhibition in the simulated cortical network. 3. The balance between excitation and inhibition is a key factor in determining the stability of the network model. There is a large excitation-inhibition (E-I) parameter region within which the model can stably respond to inputs. 4. The input-output relations and receptive field (RF) sizes of simulated neurons are modifiable by the E-I balance. The shapes of RFs are determined by both feedforward projections and the spatial distribution of lateral connections. 5. We simulated changes in temporal and spatial properties of neurons in response to manipulations that mimic bicuculine methiodide or glutamate application to the cortex. Simulation results agreed well with experimental data, suggesting that cortical transmitter levels play an important role in the dynamic responses of the neural net through their effects on E-I balance. 6. With parameters of the model set to an inhibition-dominant scheme, the model was able to reproduce experimentally observed rapid RF expansions that follow cortical lesion or input denervation. Simulation results also suggested that spontaneous inputs to a sensory system can serve as a source of tonic inhibition in the cortex. 7. We conclude that lateral connections could produce and maintain a cortical network having dynamic properties without the need to invoke synaptic plasticity. Individual neuron properties could be modified by changing the balance of cortical layer excitation and inhibition. In a real brain, this could be achieved either by changing levels of cortical transmitter (gamma-aminobutyric acid. for example) or by changing tonic background input to the cortical network.


The role of heavy drinking in the risk of traffic fatalities.
Recent studies have identified a "hard core" of drinking drivers who do not fit a "social" drinker profile and may require medical intervention. This article builds on these studies by quantifying the role of heavy drinking in motor vehicle fatalities. Data on male alcohol-involved fatally injured drivers (AIFIDs) were obtained from the U.S. Fatal Accident Reporting System (FARS) for the years 1989-1990 (n = 8876). The AIFIDs were grouped into either a "heavy" or "light" drinking category based on drinking behaviors inferred from prior driving records and blood alcohol concentrations (BAC). The majority of male AIFIDs were between the ages of 20-39 (70%). Sixty-five percent had a BAC of 150 mg/dl or greater, and 41% had a BAC in excess of 200 mg/dl. AIFIDs with high BACs were more likely to have histories of DUI convictions and license suspensions than AIFIDs with low BACs. According to the study's criteria, 73% percent of the AIFIDs could be classified as "heavy" drinkers. There were no driving variables that differentiated the heavy and light drinker groups, indicating that heavy drinking per se is the primary factor that distinguishes the groups. Male alcohol-involved fatally injured drivers are comprised mostly of heavy drinkers who may suffer from serious drinking problems or alcoholism. Successful interventions may require medical treatment as well as punitive criminal justice policies.


Predictive Role of Tumor-Stroma Ratio for Survival of Patients With Non-Small Cell Lung Cancer: A Meta-Analysis.
Background: Role of tumor-stroma ratio (TSR) as a predictor of survival in patients with non-small cell lung cancer (NSCLC) remains not clear. A systematic review and meta-analysis was conducted to summarize current evidence for the role of TSR in NSCLC. Methods: Relevant cohort studies were retrieved via search of Medline, Embase, and Web of Science databases. The data was combined with a random-effect model by incorporating the between-study heterogeneity. Specifically, subgroup and meta-regression analyses were performed to explore the association between TSR and survival in patients with squamous cell carcinoma (SCC) or adenocarcinoma (AC). Results: Nine cohort studies with 2031 patients with NSCLC were eligible for the meta-analysis. Pooled results showed that compared to those stroma-poor tumor, patients with stroma rich NSCLC were associated with worse recurrence-free survival (RFS, hazard ratio [HR] = 1.52, 95% confidence interval [CI]: 1.07 to 2.16, p = 0.02) and overall survival (OS, HR = 1.48, 95% CI: 1.20 to 1.82, p < 0.001). Subgroup analyses showed that stroma-rich tumor may be associated with a worse survival of SCC (HR = 1.89 and 1.47 for PFS and OS), but a possibly favorable survival of AC (HR = 0.28 and 0.69 for PFS and OS). Results of meta-regression analysis also showed that higher proportion of patients with SCC was correlated with higher HRs for RFS (Coefficient = 0.012, p = 0.03) and OS (Coefficient = 0.014, p = 0.02) in the included patients, while higher proportion of patients with AC was correlated with lower HRs for RFS (Coefficient = -0.012, p = 0.03) and OS (Coefficient = -0.013, p = 0.04), respectively. Conclusion: Tumor TSR could be used as a predictor of survival in patients with NSCLC. The relative proportion of patients with SCC/AC in the included NSCLC patients may be an important determinant for the association between TSR and survival in NSCLC. Stroma richness may be a predictor of poor survival in patients with lung SCC, but a predictor of better survival in patients with lung AC.


Impact of dietary fatty acid supplementation on renal injury in obese Zucker rats.
We previously reported that renal injury in hyperlipidemic, obese Zucker rats was associated with a relative deficiency of tissue polyunsaturated fatty acids (PUFA). In the present study 10-week-old obese Zucker rats were pair fed regular chow or chow containing either 20% sunflower oil rich in n-6 PUFA, fish oil rich in n-3 PUFA, coconut oil medium-chain saturated fatty acid, or beef tallow long-chain saturated fatty acid. At 34 weeks of age there were comparable reductions in albuminuria, mesangial matrix expansion, and glomerulosclerosis in the fish oil and sunflower oil groups. While both fish oil and sunflower oil reduced serum triglycerides, and improved the composition of triglyceride-enriched lipoproteins, only fish oil decreased serum cholesterol. The effect of the dietary fatty acid supplementation on fatty acid profiles were similar in isolated glomeruli and cortical tissue. In general, the amelioration in injury in the fish oil and sunflower oil fed rats was most closely linked to glomerular levels of PUFA, either n-6 or n-3. These data suggest that hyperlipidemia and abnormalities in tissue FA are closely linked, and that dietary supplementation with PUFA may ameliorate chronic, progressive renal injury.


Impact of knee osteoarthritis on health care resource utilization in a US population-based national sample.
We sought to estimate the impact of knee osteoarthritis (OA) on health care utilization. Using the 2003 Medicare Current Beneficiary Survey, a population-based survey of Medicare beneficiaries linked to Medicare claims, we selected a national cohort of community-dwelling persons aged 65 and older with knee OA and a sex- and age-matched comparison cohort without any form of OA. We distinguished following 4 components of health care utilization: physician (MD) office visits, non-MD office visits, inpatient hospital stays, and emergency department visits. We built multiple regression models to determine whether knee OA affects utilization, controlling for comorbidity count, obesity, functional limitation, education, race, and working status. A total of 545 Medicare Current Beneficiary Survey participants with knee OA were matched with 1090 OA-free individuals. Mean age in both cohorts was 76 years; approximately 70% were female. Knee OA and OA-free subjects differed significantly in obesity (Knee OA: 37%, OA-free: 20%), % with >or=2 comorbidities (Knee OA: 69%, OA-free: 43%), and functional limitation (Knee OA: 42%, OA-free: 26%). In multivariable regression models, the knee OA cohort had on average 6.0 more annual MD visits (95% confidence interval [CI]: 4.7, 7.4) and 3.8 more non-MD visits (95% CI: 2.8, 4.7) than the OA-free cohort. The knee OA cohort also had 28% more hospital stays (odds ratio [OR] = 1.3, 95% CI: 1.0, 1.6), a difference attributable to total joint replacements. This first national, population-based study of health care utilization in persons with knee OA documents considerable excess utilization attributable to knee OA, independent of comorbidity, and other patient characteristics.


Radicals from the gas-phase pyrolysis of catechol: 1. o-Semiquinone and ipso-catechol radicals.
The formation of environmentally persistent free radicals (EPFRs) from the gas-phase pyrolysis of catechol (CT) was studied over a temperature range of 400-750 degrees C using the technique of low-temperature matrix isolation electron paramagnetic resonance (LTMI-EPR) spectroscopy. A split singlet EPR spectrum with a g value of 2.0052 was observed. To aid in the interpretation of this spectrum, a detailed analysis of the potential energy surface of CT decomposition pathways was performed employing CBS-QB3 multilevel and DFT individual methods. The energetically favored channels were the formation of ipso- and alpha-CT isomers of CT as well as o-semiquinone (o-SQ) radicals from ipso- and alpha-CT. ipso-CT as well as open ipso-CT radicals were apparently unstable intermediates that could not be accumulated in sufficiently high concentrations to be detected by EPR. The calculated EPR spectrum of o-SQ radical is consistent with the formation of an oxygen-centered radical with a high g value observed experimentally. The hyperfine splitting of the observed spectrum can be attributed to the formation of hydrogen bonds in radical dimers. The lack of experimental observation of o-benzoquinone, an anticipated pyrolysis product, has been explained based on theoretical calculations.


The likely role of vitamin D from solar ultraviolet-B irradiance in increasing cancer survival.
Solar ultraviolet-B (UVB) and vitamin D have been found inversely correlated with cancer incidence, mortality, and survival rates in many studies. In this work, two sets of cancer data were used: age-adjusted cancer incidence and mortality rates in 2002 for 21 Western developed countries and cancer survival data from Eurocare-3 for nine European countries for cancer diagnosed from 1990 to 1994. The data were used in ecologic studies with respect to latitude, an index of solar UVB irradiance, and dietary supply factors for 1985. Statistically significant correlations of effective or actual survival rates with increasing latitude were found for breast, colon, gastric, lung, ovarian, pancreatic, prostate and renal cancer, and non-Hodgkin's lymphoma. Five-year survival rates south of 50 degrees N were 20%-50% higher than those near 55 degrees N. These results provide additional support for an increase in cancer survival rates linked with natural vitamin D.


Atrial fibrillation after taser exposure in a previously healthy adolescent.
We are reporting a previously healthy adolescent who developed atrial fibrillation after being tased. He has a structurally normal heart on echocardiogram, normal electrolyte level and thyroid function test results, and a urine toxicology screen positive for marijuana. The patient ultimately required external defibrillation to convert his cardiac rhythm to normal sinus rhythm and has had no recurrent arrhythmias since hospital discharge (approximately 1 year). This is the first reported case of atrial fibrillation developing after a Taser shot, occurring in an adolescent without other risk factors. This case illustrates the arrhythmogenic potential of a Taser in otherwise healthy young individuals, and further study of occurrence of Taser-induced arrhythmias is warranted.


Maize Photosystem I : Identification of the Subunit which Binds Plastocyanin.
Photosystem I (PSI) has been isolated from mesophyll chloroplasts of mature maize leaves. The isolated PSI (PSI-200) was used as starting material for preparing an antenna-depleted core (PSI-100). Both of these preparations appear to be quite analogous to PSI complexes isolated from other plant tissue sources, such as those from C3 plants, as judged from NADP photoreduction assays, immunoblotting, and the ability of the complexes to form a covalent crosslinked product with spinach plastocyanin. The study suggests that the PSI complex from a C4 plant is similar to that isolated from a C3 plant in that both contain the plastocyanin docking protein although the apparent molecular weight of these respective subunits differ slightly.


First Identification and Genotyping of Enterocytozoon bieneusi and Prevalence of Encephalitozoon intestinalis in Patients with Acute Diarrhea in the Republic of Korea.
Encephalitozoon intestinalis and Enterocytozoon bieneusi can cause diarrhea in humans, especially severe diarrhea in immunocompromised patients. However, there have been few studies on Enc. intestinalis and Ent. bieneusi in patients with acute diarrhea in the Republic of Korea (ROK). In this study, fecal samples were collected from 1241 patients with acute diarrhea in 2020. Among these, 24 cases of Enc. intestinalis and one case of Ent. bieneusi were detected via PCR amplification of small subunit ribosomal RNA. Genotyping of the internal transcribed spacer region sequence revealed that the detected Ent. bieneusi genotype was in Group 1. This study provides the first evidence that Ent. bieneusi exists in humans in addition to animals in the ROK. To identify the causative agent, continuous monitoring of Enc. intestinalis and Ent. bieneusi is necessary for patients with acute diarrhea in the ROK.


Facial and other non-verbal communicative behaviour in chronic schizophrenia.
Facial behaviour may be an important determinant in clinical ratings of psychopathology. A standardized objective technique was used to quantify measures of facial behaviour in 21 chronic schizophrenic subjects, in comparison with control groups of depressed, demented and Parkinsonian subjects. Facial behaviours were counted and timed from video recordings of each subjects' face during a clinical interview. Separate measurement of behaviours were obtained while subjects were speaking and silent. For most variables, the amount of facial behaviour was significantly less in schizophrenic subjects than in control groups. The groups differed significantly on a number of measures, but schizophrenics could not be reliably identified by a single facial behaviour variable. However, using a discriminant function analysis with measures for eye contact while speaking and silent, broad smiles and small smiles, discrimination between groups was good, with over 80% correctly classified as either schizophrenic, or not schizophrenic. These techniques may increase our understanding of psychopathological signs and the mechanisms that underly them.


Generation, Characterization and Application of Antibodies Directed against HERV-H Gag Protein in Colorectal Samples.
A substantial part of the human genome originates from transposable elements, remnants of ancient retroviral infections. Roughly 8% of the human genome consists of about 400,000 LTR elements including human endogenous retrovirus (HERV) sequences. Mainly, the interplay between epigenetic and post-transcriptional mechanisms is thought to silence HERV expression in most physiological contexts. Interestingly, aberrant reactivation of several HERV-H loci appears specific to colorectal carcinoma (CRC). The expression of HERV-H Gag proteins (Gag-H) was assessed using novel monoclonal mouse anti Gag-H antibodies. In a flow cytometry screen four antibody clones were tested on a panel of primary CRC cell lines and the most well performing ones were subsequently validated in western blot analysis. Finally, Gag-H protein expression was analyzed by immune histology on cell line cytospins and on clinical samples. There, we found a heterogeneous staining pattern with no background staining of endothelial, stromal and infiltrating immune cells but diffuse staining of the cytoplasm for positive tumor and normal crypt cells of the colonic epithelium. Taken together, the Gag-H antibody clone(s) present a valuable tool for staining of cells with colonic origin and thus form the basis for future more detailed investigations. The observed Gag-H protein staining in colonic epithelium crypt cells demands profound analyses of a potential role for Gag-H in the normal physiology of the human gut.


The fertile eunuch variant of idiopathic hypogonadotropic hypogonadism: spontaneous reversal associated with a homozygous mutation in the gonadotropin-releasing hormone receptor.
Mutations in the GnRH receptor (GnRH-R) gene have been reported to cause idiopathic hypogonadotropic hypogonadism (IHH). Herein, we describe a 26-yr-old male with a mild phenotypic form of IHH, the fertile eunuch syndrome (IHH in the presence of normal testicular size and some degree of spermatogenesis), associated with a homozygous mutation (Gln106Arg) in the GnRH-R. This mutation, located in the first extracellular loop of the GnRH-R, has been previously shown to decrease but not eliminate GnRH binding. The proband had hypogonadal testosterone levels, detectable but apulsatile gonadotropin secretion, and a normal adult male testicular size of 17 mL at baseline. After only 4 months of treatment with hCG alone, he developed sperm in his ejaculate and his wife conceived. Following cessation of hCG therapy, the patient demonstrated reversal of his hypogonadotropism as evidenced by normal adult male testosterone levels and the appearance of pulsatile luteinizing hormone secretion. This case thus expands the emerging clinical spectrum of GnRH-R mutations, provides the first genetic basis for the fertile eunuch variant of IHH and documents the occurrence of reversible IHH in a patient with a GnRH-R mutation.


Response of IMCD3 cells to hypertonic challenges as analyzed by electron microscopy.
This work defines the ultrastructural responses of immortalized cells from the inner medullary collecting duct cells (IMCD3 cells) to hypertonic challenges. The cultured cells were either acutely exposed to hypertonic medium (550 mOsm/kgH₂O) for 24-72 h or gradually adapted to 600 or 900 mOsm/kgH₂O media with sodium chloride. After short (24 h) hypertonic challenges, there was an expansion of the Golgi apparatus with distinct expression of the γ subunit of Na,K-ATPase. The frequency of active caspase-3-positive cells was unchanged as was also the measured activity of caspase-3. Immunoelectron microscopy showed that active caspase-3 in the positive cells was localized in cytoplasmic bodies 0.5-1 μm in diameter but not in other structures. Apoptotic bodies with the nuclei were only rarely observed following acute hypertonicity for 24 to 72 h. Following prolonged hypertonic challenges, some cells showed condensation of the chromatin but still few apoptotic bodies. Gradual hypertonicity to 900 mOsm/kgH₂O led to a decrease of microvilli, dilated cisternae of the endoplasmic reticulum (ER), increased abundance of free ribosomes and longitudinal mitochondrial cristae. Virus particles were present inside and outside the cells in all experimental conditions and appeared unrelated to the apoptotic process. The results suggest that cultured IMCD3 cells are resistant to short hypertonic challenge or gradual adaptation to moderate hypertonicity and only rarely exhibit more ultrastructural apoptotic changes than control cells. The presence of caspase-3-containing bodies is a novel finding, and we suggest that they arise from the ER and are involved in the apoptotic signaling system.


Assessment of the effect of phenytoin on cutaneous healing from excision of melanocytic nevi on the face and on the back.
Topical phenytoin is a powerful skin wounds healing and it may be useful in clinical practice. The purpose of this study was to evaluate the effect of topical phenytoin 0.5%, by comparing it with cream (control) in wounds resulting from excision of two melanocytic nevi in the same patient. Our purpose was also to assess if phenytoin had better therapeutic and cosmetic outcomes when compared with cream (control). This study evaluated 100 patients with skin wounds from excision of melanocytic nevi. 50 patients with lesions on the face and 50 patients with lesions on the back, totalizing 200 lesions excised with modified punch. The resulting superficial skin wounds had the same diameter and depth, and second intention healing followed.Patients were followed for 60 days. Student's t-test, Mann Whitney nonparametric test, analysis of variance, LSD test, Shapiro-Wilks test and Fisher test were used to analyze the results, depending on the nature of the variables being studied. Phenytoin showed better therapeutic and cosmetic results, by healing faster, with more intense epithelization in wounds in comparison with cream (control). Phenytoin showed a statistically significant difference regarding the following parameters (p < 0.05): wounded area and healing time. Phenytoin application resulted in a smaller area and a shorter healing time. Also the intensity of exudates, bleeding, and the epithelization were more intense in phenytoin-treated wounds. Regarding the shape and thickness of the scar, injuries treated with phenytoin had round and flat shaped scars in most of the cases. Considering patient's gender and phototype, female patients presented smaller wounds and scar areas; and phototype I had the largest scar areas. Contact eczema was an adverse reaction in 7 injuries located on the back caused by cream (control) and hypoallergenic tape. Phenytoin showed better therapeutic and cosmetic results compared with cream (control). Phenytoin is a low cost drug, which accelerates skin wounds healing in human patients. ISRCTN96539803.


Efficacy of blanket treatment of cows and heifers with an internal teat sealant in reducing the risk of mastitis in dairy cattle calving on pasture.
To evaluate the benefit of blanket treatment of all milking cows at drying-off and all replacement heifers one month prior to the planned start of mating with an internal teat sealant on the incidence of mastitis, and somatic cell counts (SCC), postpartum in a 650-cow herd with a mastitis incidence in early lactation of 15% in cows and 26% in heifers. Prior to drying-off, lactating cattle were divided on the basis of SCC and mastitis history. Cattle with records of individual SCC >150,000 cells/ml or mastitis in the previous lactation were treated with a cloxacillin-based dry-cow therapy (DCT), while the remaining cattle received no antibiotics. Cattle in each of the two groups were then randomly assigned to receive either an internal teat sealant or no further treatment. Additionally, one month prior to the planned start of calving the rising 2-year-old heifers were also randomly assigned to receive either an internal teat sealant or no treatment. All clinical mastitis cases were recorded for the first 10 weeks after the start of calving, while SCC were measured on three occasions during the subsequent lactation. Data were available from 466 cows and 206 heifers; treatment with the internal teat sealant significantly reduced the incidence of mastitis in both groups. For cows, the reduced risk of mastitis due to treatment with the teat sealant was not significantly different between cows, which, based on their mastitis history, required dry-cow antibiotics and those which did not. There was no effect of teat sealant on the mean SCC of any group at any time-point. On this farm, treatment of all cows and heifers prior to parturition with an internal teat sealant significantly reduced the risk of clinical mastitis. The benefits of an internal teat sealant were the same when used in combination with antibiotics in cows with a history of mastitis as when used alone in cows with no such history. These data support the proposition that blanket treatment with an internal teat sealant of all cows due to enter the milking herd can be a useful method of mastitis control. They also suggest that combined therapy with dry-cow antibiotics and internal teat sealants can be beneficial under New Zealand conditions. More detailed research on more farms in more areas of New Zealand is required to confirm these suggestions.


How Children Use Active Videogames and the Association Between Screen Time and Physical Activity.
The energy required to play active videogames (AVGs) has been reported on in the literature; however, little is known about how children use such games in their home environment. The aim of this study was to investigate children's use of AVGs and the association among AVG use, other screen-based activities, and physical activity levels. Eight hundred and twenty children 12.1 (0.6) years of age participated. Physical activity levels, sedentary screen-based activities, and AVG use were investigated. Differences across genders and deprivation indices were also analyzed. Fifty-eight percent of children met minimal physical activity guidelines. Forty-seven percent of children exceeded screen time recommendations. Of those who had access to AVGs, more children played sedentary games (or active games in a sedentary manner [68 percent]) than active games (55 percent) on AVG consoles. Furthermore, sedentary games were played for longer than active games. AVG play was positively correlated with reported time spent watching television (P=0.02). In free-living conditions AVG consoles are being used by more children and for longer durations as sedentary screen-based devices rather than active screen-based devices.


Visual-feedback therapy for antipsychotic medication adherence.
This pilot study aimed to examine the effectiveness of visual-feedback therapy for individuals with psychotic disorders. Visual-feedback therapy combines structured psychodynamic therapy and visual feedback achieved via an electronic monitoring medication cap to increase insight about medication behaviours. Thirty subjects were randomly assigned either to visual feedback or to a supportive counselling group. Medication adherence was measured by both electronic monitoring and blood plasma drug concentration levels. The results showed that, at the end of the 3-month, intervention (bimonthly sessions), adherence rates of the visual-feedback group slightly increased, but declined during the course of the study for the supportive counselling control group (P=0.026).


Tobacco smoking increases dramatically air concentrations of endotoxin.
We used a mass spectrometry-based assay for identifying the endotoxin (lipopolysaccharide, LPS) marker (R)-3-hydroxytetradecanoic acid in cigarette smoke particles and found that smoking involved inhalation of 17.4 pmol of endotoxin per each smoked cigarette. Indoor exposure to environmental tobacco smoke (ETS) entailed inhalation of 12.1 pmol of LPS/m3 air, an amount that was 120 times higher than the levels found in smoke-free indoor air. Endotoxin is one of the most potent inflammatory agents known, hence our results may help to explain the high prevalence of respiratory disorders among smokers, and they may also draw attention to a hitherto unknown or neglected risk factor of ETS. Endotoxin represents a largely neglected risk factor of smoking and passive smoking and this knowledge may lead to a reduced smoking.


Day-Night Variations in Malate Concentration, Osmotic Pressure, and Hydrostatic Pressure in Cereus validus.
Malate concentration and stem osmotic pressure concomitantly increase during nighttime CO(2) fixation and then decrease during the daytime in the obligate Crassulacean acid metabolism (CAM) plant, Cereus validus (Cactaceae). Changes in malate osmotic pressure calculated using the Van't Hoff relation match the changes in stem osmotic pressure, indicating that changes in malate level affected the water relations of the succulent stems. In contrast to stem osmotic pressure, stem water potential showed little day-night changes, suggesting that changes in cellular hydrostatic pressure occurred. This was corroborated by direct measurements of hydrostatic pressure using the Jülich pressure probe where a small oil-filled micropipette is inserted directly into chlorenchyma cells, which indicated a 4-fold increase in hydrostatic pressure from dusk to dawn. A transient increase of hydrostatic pressure at the beginning of the dark period was correlated with a short period of stomatal closing between afternoon and nighttime CO(2) fixation, suggesting that the rather complex hydrostatic pressure patterns could be explained by an interplay between the effects of transpiration and malate levels. A second CAM plant, Agave deserti, showed similar day-night changes in hydrostatic pressure in its succulent leaves. It is concluded that, in addition to the inverted stomatal rhythm, the oscillations of malate markedly affect osmotic pressures and hence water relations of CAM plants.


A human thermoregulation model for the Chinese elderly.
Older people are always more vulnerable to thermal-related discomfort and health issues because of their diminishing ability to adapt to varying environmental conditions. There exist a few thermoregulation models but most of them did not consider age and ethnic differences. In this study, a standard thermoregulation model for Chinese elders was developed on the basis of literature review and the already established model for the Chinese young people. Furthermore, the standard model was individualized with four parameters (height, weight, sex and age) for more accurate prediction. Besides, both models were validated with experimental data. Results show that the standard model prediction-measurement discrepancies of the skin temperatures lay in the range of S.D. of measurements. Compared to the standard model, there were some improvements in the individualized model, especially for old men. Further validation with published experimental data indicated good predictions were also in good agreement with measurements. The work in the paper may play an important role in providing a more healthy and comfortable indoor environment for the elderly.


Association of hsp70-2 and hsp-hom gene polymorphisms with risk of acute high-altitude illness in a Chinese population.
High-altitude illness (HAI) is a potentially fatal condition involving genetic and environmental components. Accumulated experimental evidence suggests that heat shock proteins (Hsps), especially HSP70, can protect cells and organs against different types of damage. We investigated whether genetic variation in constitutive and inducible hsp70 genes could be associated with risk of HAI. The association between polymorphisms of the HSP70 family genes and risk of HAI was determined in 56 patients with HAI and in 100 matched controls by genotyping for the polymorphisms +190 G/C, +1267 A/G, 2437 G/C in the hsp70-1, hsp70-2, and hsp70-hom genes by using polymerase chain reaction-restriction fragment length polymorphism. The data showed that there was no statistically significant difference in the genotype and allele distributions of hsp70-1, in hsp70-2 allele and hsp70-2 A/A and A/B genotypes, and in allele distribution of hsp70-hom among patients with HAI and controls (chi2 test, P > 0.05). However, there was a significantly higher frequency of hsp70-2 B/B and hsp70-hom A/A and B/B genotypes and a significantly lower frequency of the hsp70-hom A/B genotype in the HAI patients compared with the controls (P < 0.05 for all). The risk associated with the hsp70-2 B/B and hsp70-hom A/A, A/B, and B/B genotypes were 4.017 (95% CI = 1.496-10.781; P = 0.004), 2.434 (95% CI = 1.184-5.003; P = 0.012), 0.299 (95% CI = 0.148-0.602, P = 0.001), and 5.880 (95% CI =1.145-30.196, P = 0.026), respectively. Our results suggest that individuals with hsp70-2 B/B and hsp70-hom A/B and B/B genotypes may be more susceptible to HAI, whereas those with hsp70-hom A/B genotype may be tolerant to HAI. Further studies in individuals of different age and sex are warranted to elucidate the underlying mechanisms of this association and the possible functions of different genotypes of hsp70-2 and hsp70-hom under hypoxic stress.


Trefoil factor 1 as a marker of mucosal damage of the gastrointestinal tract in children with sepsis.
Intestinal ischemia and reperfusion is a common pathway for many diseases in children. The objective of our study was an analysis of Trefoil factor 1 levels dynamics in patients with SIRS or septic condition during a 5-day period. Analysis of TFF1 levels dynamics revealed that TFF1 levels kept steady state during the 5-day period. TFF1 levels were similar in patients with SIRS, sepsis and severe sepsis. Significantly higher levels of TFF1 were in patients with septic shock and MODS.


Investigating DNA hydrogels as a new biomaterial for enzyme immobilization in biobatteries.
We report the usage of DNA hydrogels for enzyme entrapment in an enzymatic biobattery. With the recent advancements in DNA nanotechnology, the incorporation of DNA materials to bioelectrocatalytic electrodes holds great promise to improve the performance of bioelectrocatalysis-based devices.


Stem cell therapy and tissue engineering for correction of congenital heart disease.
This review article reports on the new field of stem cell therapy and tissue engineering and its potential on the management of congenital heart disease. To date, stem cell therapy has mainly focused on treatment of ischemic heart disease and heart failure, with initial indication of safety and mild-to-moderate efficacy. Preclinical studies and initial clinical trials suggest that the approach could be uniquely suited for the correction of congenital defects of the heart. The basic concept is to create living material made by cellularized grafts that, once implanted into the heart, grows and remodels in parallel with the recipient organ. This would make a substantial improvement in current clinical management, which often requires repeated surgical corrections for failure of implanted grafts. Different types of stem cells have been considered and the identification of specific cardiac stem cells within the heterogeneous population of mesenchymal and stromal cells offers opportunities for de novo cardiomyogenesis. In addition, endothelial cells and vascular progenitors, including cells with pericyte characteristics, may be necessary to generate efficiently perfused grafts. The implementation of current surgical grafts by stem cell engineering could address the unmet clinical needs of patients with congenital heart defects.


Comparison of Superelasticity of Nickel Titanium Orthodontic Arch wires using Mechanical Tensile Testing and Correlating with Electrical Resistivity.
Application of light and continuous forces for optimum physiological response and least damage to the tooth supporting structures should be the primary aim of the orthodontist. Nickel titanium alloys with the properties of excellent spring back, super elasticity and wide range of action is one of the natural choices for the clinicians to achieve this goal. In recent periods, various wire manufacturers have come with a variety of wires exhibiting different properties. It is the duty of the clinician to select appropriate wires during various stages of treatment for excellent results. For achieving this evaluation of the properties of these wires is essential. This study is focussed on evaluating the super elastic property of eight groups of austenite active nickel titanium wires. Eight groups of archwires bought from eight different manufacturers were studied. These wires were tested through mechanical tensile testing and electrical resistivity methods. Unloading curves were carefully assessed for superelastic behaviour on deactivation. Rankings of the wires tested were based primarily upon the unloading curve's slope Conclusion: Ortho organisers wires ranked first and superior, followed by American Orthodontics and Ormco A wires. Morelli and GAClowland NiTi wires were ranked last. It can be concluded that the performance of these wires based on rankings should be further evaluated by clinical studies. How to cite this article: Sivaraj A. Comparison of Superelasticity of Nickel Titanium Orthodontic Arch wires using Mechanical Tensile Testing and Correlating with Electrical Resistivity. J Int Oral Health 2013; 5(3):1-12.


Bortezomib induces schedule-dependent modulation of gemcitabine pharmacokinetics and pharmacodynamics in non-small cell lung cancer and blood mononuclear cells.
Bortezomib combination with gemcitabine/cisplatin in patients with advanced tumors, predominantly non-small cell lung cancer (NSCLC), showed an unexpected transient drop in the deoxycytidine plasma levels, a marker for gemcitabine activity. This study investigates the pharmacokinetic/pharmacodynamic effect of bortezomib on gemcitabine in NSCLC and peripheral blood mononuclear cells (PBMC). Gemcitabine metabolites, including difluoro-dCTP (dFdCTP), were studied in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients and from volunteers and NSCLC cells (H460 and SW1573) exposed to 4 h simultaneous or sequential treatments of gemcitabine (50 μmol/L, 4 h) and bortezomib (100 nmol/L, 2 h). Gemcitabine total phosphate levels measured by liquid chromatography-tandem mass spectrometry in PBMCs from bortezomib/gemcitabine/cisplatin-treated patients were strongly reduced after 90 min (-82.2%) up to 4 h post-gemcitabine infusion compared with gemcitabine/cisplatin-treated patients. Accordingly, bortezomib/gemcitabine combinations reduced dFdCTP in PBMCs treated ex vivo. Surprisingly, differential effects were observed in NSCLC cells. dFdCTP decreased after 4 h following gemcitabine removal in H460 but continued to increase for 24 h in SW1573. However, dFdCTP significantly increased (2-fold) in both cell lines in the bortezomib → gemcitabine exposure, coinciding with a major reduction in cell growth compared with single drugs, and the highest increase of deoxycytidine kinase expression, possibly mediated via E2F-1. Bortezomib affects differently gemcitabine pharmacokinetics/pharmacodynamics in PBMCs and NSCLC cells, suggesting that PBMCs are not adequate to evaluate the anticancer activity of bortezomib/gemcitabine combinations. The bortezomib → gemcitabine/cisplatin schedule appeared a safe and active combination for the treatment of advanced NSCLC and the bortezomib → gemcitabine was the most cytotoxic combination in NSCLC cells. The increase of deoxycytidine kinase and dFdCTP might contribute to this synergistic interaction and supports its further clinical investigation.


Effect of Mg-Gluconate on the Osmotic Fragility of Red Blood Cells, Lipid Peroxidation, and Ca2+-ATPase (PMCA) Activity of Placental Homogenates and Red Blood Cell Ghosts From Salt-Loaded Pregnant Rats.
Preeclampsia (PE) is a pregnancy-specific syndrome with multisystem involvement which leads to fetal, neonatal, and maternal morbidity and mortality. A model of salt-loaded pregnant rats has been previously studied, sharing several pathological characteristics of preeclamptic women. In this study, it was compared the effects of the treatment with an oral magnesium salt, magnesium gluconate (Mg-gluconate), on the osmotic fragility of red blood cells, lipid peroxidation, and PMCA activity of placental homogenates and red blood cell ghosts in salt-loaded pregnant rats. Mg-gluconate has a higher antioxidant capacity than MgSO4 due to the presence of several hydroxyl groups in the two anions of this salt. Salt-loaded pregnant rats received 1.8% NaCl solution ad libitum as a beverage during the last week of pregnancy. On day 22nd of pregnancy, the rats were euthanized and red blood cells and placenta were obtained. Salt-loaded pregnant rats showed an increased level of lipid peroxidation and a lowered PMCA activity in placental and red blood cell ghosts, as well as an increased osmotic fragility of their red blood cells. The treatment of the salt-loaded pregnant rats with Mg-gluconate avoids the rise in the level of lipid peroxidation and the concomitant lowering of the PMCA activity of their red blood cell membranes, reaching values similar to those from control pregnant rats. Also, this treatment prevents the increase of the osmotic fragility of their red blood cells, keeping values similar to those from control pregnant rats. Mg-gluconate seems to be an important candidate for the replacement of the MgSO4 treatment of preeclamptic women.


C-fos down-regulation inhibits testosterone-dependent male sexual behavior and the associated learning.
Environmental stimulation results in an increased expression of transcription factors called immediate early genes (IEGs) in specific neuronal populations. In male Japanese quail, copulation with a female increases the expression of the IEGs zenk and c-fos in the medial pre-optic nucleus (POM), a key nucleus controlling male sexual behavior. The functional significance of this increased IEG expression that follows performance of copulatory behavior is unknown. We addressed this question by repeatedly quantifying the performance of appetitive (learned social proximity response) and consummatory (actual copulation) sexual behavior in castrated, testosterone-treated males that received daily intra-cerebroventricular injection of an antisense oligodeoxynucleotide targeting c-fos or control vehicle. Daily antisense injections significantly inhibited the expression of copulatory behavior as well as the acquisition of the learned social proximity response. A strong reduction of the proximity response was still observed in antisense-treated birds that copulated with a female, ruling out the indirect effect of the absence of interactions with females on the learning process. After a 2-day interruption of behavioral testing but not of antisense injections, birds were submitted to a final copulatory test that confirmed the behavioral inhibition in antisense-injected birds. Brains were collected at 90 min after the behavioral testing for quantification of c-fos-immunoreactive cells. A significant reduction of the number of c-fos-positive cells in the POM but not in other brain regions was observed following antisense injection. Taken together, the data suggest that c-fos expression in the POM modulates copulatory behavior and sexual learning in male quail.


Ratings of different olfactory judgements in schizophrenia.
We assessed the influence of schizophrenia on different olfactory tasks. Forty patients with schizophrenia (20 males and 20 females) and 40 control subjects (20 males and 20 females) were tested. The experiment included two sessions. Initially, 12 odorants were presented at a rate of one per minute. The subjects were asked to rate intensity, pleasantness, familiarity and edibility for each odour using linear rating scales. The odorants were then presented a second time and the subjects were asked to identify them. The results showed that the scores for pleasantness, familiarity, edibility and identification but not intensity were disturbed in patients when compared with control subjects. Furthermore, the familiarity judgement of male patients was more often deficient than that of female patients and they rated odorants as being inedible when the women judged them as neutral. Considered together, these data show that our olfactory test may be used in patients with schizophrenia for evidencing various dysfunctions specific to different types of olfactory processing that represent steps in the odour name identification process.


Longitudinal Changes of COVID-19 Symptoms in Social Media: Observational Study.
In December 2019, the COVID-19 outbreak started in China and rapidly spread around the world. Many studies have been conducted to understand the clinical characteristics of COVID-19, and recently postinfection sequelae of this disease have begun to be investigated. However, there is little consensus on the longitudinal changes of lasting physical or psychological symptoms from prior COVID-19 infection. This study aims to investigate and analyze public social media data from Reddit to understand the longitudinal impact of COVID-19 symptoms before and after recovery from COVID-19. We collected 22,890 Reddit posts that were generated by 14,401 authors from March 14 to December 16, 2020. Using active learning and intensive manual inspection, 292 (2.03%) active authors, who were infected by COVID-19 and frequently reported disease progress on Reddit, along with their 2213 (9.67%) longitudinal posts, were identified. Machine learning tools to extract biomedical information were applied to identify COVID-19 symptoms mentioned in the Reddit posts. We then examined longitudinal changes in individual physiological and psychological characteristics before and after recovery from COVID-19 infection. In total, 58 physiological and 3 psychological symptoms were identified in social media before and after recovery from COVID-19 infection. From the analyses, we found that symptoms of patients with COVID-19 lasted 2.5 months. On average, symptoms appeared around a month before recovery and remained for 1.5 months after recovery. Well-known COVID-19 symptoms, such as fever, cough, and chest congestion, appeared relatively earlier in patient journeys and were frequently observed before recovery from COVID-19. Meanwhile, mental discomfort or distress, such as brain fog or stress, fatigue, and manifestations on toes or fingers, were frequently mentioned after recovery and remained as intermediate- and longer-term sequelae. In this study, we showed the dynamic changes in COVID-19 symptoms during the infection and recovery phases of the disease. Our findings suggest the feasibility of using social media data for investigating disease states and understanding the evolution of the physiological and psychological characteristics of COVID-19 infection over time.


Cranial neuropathy in COVID-19: a case series and review of literature.
Neurological presentation of COVID-19 is increasingly being recognised. Cranial neuropathy in COVID-19 is an uncommon and under-diagnosed entity. We report a case series of 4 patients who presented with trigeminal neuropathy (two cases) and facial nerve palsy (two cases) which recovered with conservative treatment along with the review of the literature.


[Pain in failed back surgery syndrome].
The problems of diagnosis and treatment of Failed Back Surgery Syndrome are briefly analyzed in this article. Literature overview and analysis is supplemented by the data collected at the Spinal Neurosurgery Department in Kaunas University of Medicine Hospital during the study in which clinical findings and data were analyzed and compared to the answers of patients in the special questionnaires about pain specially designed for the patients with low back pain and the Failed Back Surgery Syndrome. During this study specially designed questionnaire was introduced for the detailed pain evaluation, McGill pain questionnaire and visual analogical scales were included in this diagnostic tool. The most important clinical aspects of diagnosis and treatment of Failed Back Surgery Syndrome are discussed in this article and compared to the clinical trial in order to point out the real their value, effectiveness and long term results. In addition, the clinical value and use of special pain questionnaires is discussed and their auxiliary role is established.


Nanoporosity, Inclusion Chemistry, and Spin Crossover in Orthogonally Interlocked Two-Dimensional Metal-Organic Frameworks.
[Fe(tvp)2 (NCS)2 ] (1) (tvp=trans-(4,4'-vinylenedipyridine)) consists of two independent perpendicular stacks of mutually interpenetrated two-dimensional grids. This uncommon supramolecular conformation defines square-sectional nanochannels (diagonal≈2.2 nm) in which inclusion molecules are located. The guest-loaded framework 1@guest displays complete thermal spin-crossover (SCO) behavior with the characteristic temperature T1/2 dependent on the guest molecule, whereas the guest-free species 1 is paramagnetic whatever the temperature. For the benzene-guest derivatives, the characteristic SCO temperature T1/2 decreases as the Hammet σp parameter increases. In general, the 1@guest series shows large entropy variations associated with the SCO and conformational changes of the interpenetrated grids that leads to a crystallographic-phase transition when the guest is benzonitrile or acetonitrile/H2 O.


Selective induction of LTP and LTD by postsynaptic [Ca2+]i elevation.
Long-term potentiation (LTP) and long-term depression (LTD), two prominent forms of synaptic plasticity at glutamatergic afferents to CA1 hippocampal pyramidal cells, are both triggered by the elevation of postsynaptic intracellular calcium concentration ([Ca2+]i). To understand how one signaling molecule can be responsible for triggering two opposing forms of synaptic modulation, different postsynaptic [Ca2+]i elevation patterns were generated by a new caged calcium compound nitrophenyl-ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid in CA1 pyramidal cells. We found that specific patterns of [Ca2+]i elevation selectively activate LTP or LTD. In particular, only LTP was triggered by a brief increase of [Ca2+]i with relatively high magnitude, which mimics the [Ca2+]i rise during electrical stimulation typically used to induce LTP. In contrast, a prolonged modest rise of [Ca2+]i reliably induced LTD. An important implication of the results is that both the amplitude and the duration of an intracellular chemical signal can carry significant biological information.


Nocturnal enuresis: what is happening?
Primary nocturnal enuresis is common and has considerable psychological ramifications for children as they get older. It is a familial condition with complex inheritance patterns. The pathophysiology of the condition appears to be related to poor arousal from sleep, nocturia due to deficient vasopressin release in sleep and possibly a decrease in functional bladder capacity especially at night. The mainstay of treatment is the bed-wetting alarm. In recent years, desmopressin nasal spray has found a clinical niche as a short-term solution for children attending school camps or sleeping over at friends' houses and as treatment in the medium term for those unresponsive to treatment with a bed-wetting alarm. It may also be used as an adjunct to the use of the alarm. Treatment with imipramine is increasingly in disfavour because the relapse rate is unacceptably high and fatal overdose is a real possibility.


Developing a regional recovery framework.
A biological attack would present an unprecedented challenge for local, state, and federal agencies, the military, the private sector, and individuals on many fronts, ranging from vaccination and treatment to prioritization of cleanup actions to waste disposal. To prepare for recovery from this type of incident, the Seattle Urban Area Security Initiative (UASI) partners collaborated with military and federal agencies to develop a regional recovery framework. The goal was to identify key information that will assist policymakers and emergency managers in shortening the timeline for recovery and minimizing the economic and public health impacts of a catastrophic anthrax attack. Based on discussions in workshops, tabletop exercises, and interviews with local, state, federal, military, and private sector entities responsible for recovery, the authors identified goals, assumptions, and concepts of operation for various areas to address critical issues the region will face as recovery progresses. Although the framework is specific to a catastrophic, wide-area biological attack using anthrax, it was designed to be flexible and scalable so it could also serve as the recovery framework for an all-hazards approach in other regions and jurisdictions. Benefits from this process include enhanced coordination and collaboration across agencies, a more thorough understanding of the anthrax threat, an opportunity to proactively consider long-term recovery, and a better understanding of the specific policy questions requiring resolution.


Low Dose Astaxanthin Treatments Trigger the Hormesis of Human Astroglioma Cells by Up-Regulating the Cyclin-Dependent Kinase and Down-Regulated the Tumor Suppressor Protein P53.
Astaxanthin (AXT) is a xanthophyll carotenoid known to have potent anti-cancer effects via upregulation of the intracellular reactive oxygen species (ROS) levels, which triggers apoptosis of cancer cells. While several studies have shown that AXT has potential as an anti-cancer drug, its effects in glioblastoma multiforme cells remain relatively unknown. In this study, we investigated the effects of AXT in the astroglioma cell lines U251-MG, T98G, and CRT-MG. We found that the response to AXT varied between cell lines. Moreover, U251-MG cells showed a specific hormetic response to AXT. At high concentrations (20-40 μM), AXT triggered apoptosis in U251-MG cells, as it has been previously shown in other cancer cell lines. However, low concentrations (4-8 μM) of AXT were found to upregulate the proliferative cell cycle. Furthermore, at low concentrations, AXT did not affect the intracellular ROS levels, while the superoxide dismutase activity increased moderately. Western blot analysis showed that treatment with a low concentration of AXT upregulated cyclin-dependent kinase (Cdk) 2 and p-Cdk2/3 levels and downregulated the expression of tumor protein p53. Thus, our results showed that AXT has a hormetic effect in the astroglioma cell line U251-MG.


Short- and long-term responses of photosynthetic capacity to temperature in four boreal tree species in a free-air warming and rainfall manipulation experiment.
High latitude forests cope with considerable variation in moisture and temperature at multiple temporal scales. To assess how their photosynthetic physiology responds to short- and long-term temperature variation, we measured photosynthetic capacity for four tree species growing in an open-air experiment in the boreal-temperate ecotone `Boreal Forest Warming at an Ecotone in Danger' (B4WarmED). The experiment factorially manipulated temperature above- and below-ground (ambient, +3.2 °C) and summer rainfall (ambient, 40% removal). We measured A/Ci curves at 18, 25 and 32 °C for individuals of two boreal (Pinus banksiana Lamb., Betula papyrifera Marsh.) and two temperate species (Pinus strobus L., Acer rubrum L.) experiencing the long-term warming and/or reduced-rainfall conditions induced by our experimental treatments. We calculated the apparent photosynthetic capacity descriptors VCmax,Ci and Jmax,Ci and their ratio for each measurement temperate. We hypothesized that (i) VCmax,Ci and Jmax,Ci would be down-regulated in plants experiencing longer term (e.g., weeks to months) warming and reduced rainfall (i.e., have lower values at a given measurement temperature), as is sometimes found in the literature, and that (ii) plants growing at warmer temperatures or from warmer ranges would show greater sensitivity (steeper slope) to short-term (minutes to hours) temperature variation. Neither hypothesis was supported as a general trend across the four species, as there was not a significant main effect (across species) of either warming or rainfall reduction on VCmax,Ci and Jmax,Ci. All species markedly increased VCmax,Ci and Jmax,Ci (and decreased their ratio) with short-term increases in temperature (i.e., contrasting values at 18, 25 and 32 °C), and those responses were independent of long-term treatments and did not differ among species. The Jmax,Ci:VCmax,Ci ratio was, however, significantly lower across species in warmed and reduced rainfall treatments. Collectively, these results suggest that boreal trees possess considerable short-term plasticity that may allow homeostasis of VCmax,Ci and Jmax,Ci to a longer term temperature treatment. Our results also caution against extrapolating results obtained under controlled and markedly contrasting temperature treatments to responses of photosynthetic parameters to more modest temperature changes expected in the near-term with climate warming in field conditions.