A noninvasive demographic assessment of sea lions based on stage-specific abundances.
A pressing need exists to develop new approaches for obtaining information on demographic rates without causing further threats to imperiled animal populations. In this paper, we illustrate and apply a data-fitting technique based on quadratic programming that uses stage-specific abundance data to estimate demographic rates and asymptotic population growth rates (lambda). We used data from seven breeding colonies of California sea lions (Zalophus californianus) in the Gulf of California, Mexico. Estimates of lambda were similar to those from previous studies relying on a diffusion approximation using trends in total abundance. On average, predicted abundances were within 24% of the observed value for the inverse estimation method and within 29% of the observed value for the diffusion approximation. Our results suggest that three of the seven populations are declining (lambda < 1), but as many as six may be at risk. Elasticity and sensitivity analyses suggest that population management in most sites should focus on the protection of adults, whose survival generally contributes the most to lambda. The quadratic programming approach is a promising noninvasive technique for estimating demographic rates and assessing the viability of populations of imperiled species.


Advances in the immune pathogenesis and treatment of multiple sclerosis.
Multiple sclerosis (MS) is a disorder of the central nervous system (CNS). It is characterized by episodic and progressive neurological dysfunction resulting from inflammatory and autoimmune reactions, myelin loss, conduction block, oligodendrocyte pathology, gliosis, and axonal loss in CNS. Recent years have witnessed advances in better understanding the immune pathogenesis of MS, prompted by animal models, human pathological observations and MRI studies. There have been significant changes in the therapeutic regimens in MS, with an emphasis on preventative treatment of an ongoing disease process. Agents in use and in the research pipeline have mechanisms that act on various anti-inflammatory and immunomodulatory properties, including blocking leukocyte migration into CNS and targeting chemoattraction. In addition, recent studies on the neurodegenerative components of MS have directed therapeutic trials to neuroprotection and neurorestoration. In this paper, we summarize the current understanding of the mechanisms of approved pharmacological agents and review the putative mechanisms and status of some important agents in clinical phase two or three trials in MS.


Pathogenic E2K mutation of doublecortin X (DCX) alters microtubule stabilisation and actin filament association.
Mutations of the microtubule (MT)-associated protein Doublecortin X (DCX) gene disrupt cortical layering in brain development. Whilst many of these pathogenic DCX mutations are within the doublecortin domains (DC1 and DC2) that mediate direct DCX-MT association, a pathogenic mutation DCX E2K that causes cognitive impairment and pachygyria in human patients lies within the regulatory DCX N-terminus (DCX-N) preceding the DC1 domain. Here, we characterise the impact of DCX E2K on cytoskeletal association and regulation in neuronal cells. We show that the DCX E2K mutant protein retains the ability to interact with and bundle MTs, but these MTs show a reduced sensitivity to nocodazole-induced depolymerisation as well as slower α-tubulin exchange rates. Furthermore, we showed increased association of DCX E2K mutant with the actin filament (F-ACT) network. These results highlight the importance of the N-terminus of DCX in regulating association and co-ordination of MT and F-ACT networks.


Secreted Factors from Stem Cells of Human Exfoliated Deciduous Teeth Directly Activate Endothelial Cells to Promote All Processes of Angiogenesis.
Diabetes is a major risk factor for atherosclerosis and ischemic vascular diseases. Recently, regenerative medicine is expected to be a novel therapy for ischemic diseases. Our previous studies have reported that transplantation of stem cells promoted therapeutic angiogenesis for diabetic neuropathy and ischemic vascular disease in a paracrine manner, but the precise mechanism is unclear. Therefore, we examined whether secreted factors from stem cells had direct beneficial effects on endothelial cells to promote angiogenesis. The soluble factors were collected as conditioned medium (CM) 48 h after culturing stem cells from human exfoliated deciduous teeth (SHED) in serum-free DMEM. SHED-CM significantly increased cell viability of human umbilical vein endothelial cells (HUVECs) in MTT assays and accelerated HUVECs migration in wound healing and Boyden chamber assays. In a Matrigel plug assay of mice, the migrated number of primary endothelial cells was markedly increased in the plug containing SHED-CM or SHED suspension. SHED-CM induced complex tubular structures of HUVECs in a tube formation assay. Furthermore, SHED-CM significantly increased neovascularization from the primary rat aorta, indicating that SHED-CM stimulated primary endothelial cells to promote comprehensive angiogenesis processes. The angiogenic effects of SHED-CM were the same or greater than the effective concentration of VEGF. In conclusion, SHED-CM directly stimulates vascular endothelial cells to promote angiogenesis and is promising for future clinical application.


Mitochondrial haplotype does not influence sperm motility in a UK population of men.
Sperm motility is regulated by mitochondrial enzymes that are partially encoded by mitochondrial DNA (mtDNA). MtDNA has therefore been suggested as a putative genetic marker of male fertility. However, recent studies in different populations have identified both significant and non-significant associations between mtDNA variation and sperm motility. Here, we tested whether mtDNA variation was associated with sperm motility in a large cohort of men from the UK, to test the robustness of previous studies and the reliability of mtDNA as a marker of poor sperm motility. A total of 463 men attending for semen analysis as part of infertility investigations were recruited from a UK laboratory. Sperm motility was measured using both computer-assisted sperm analysis and traditional manual measurements. MtDNA haplogroup and haplotype were determined in 357 and 298 men, respectively, using single nucleotide polymorphism (SNP) markers throughout the mtDNA genome, and compared with sperm motility data. The linkage between the SNP markers, and possible associations between individual SNPs and motility, were also investigated. We found no statistical association between haplogroup or haplotype and sperm motility, regardless of how it was measured (P > 0.05 in all cases). Moreover, individual SNPs which were in linkage disequilibrium and dispersed across the mitochondrial genome, and therefore sensitive to mtDNA variation, were not predictive of sperm motility. Mitochondrial haplotype is unlikely to be a reliable genetic marker of male factor infertility.


A comparative study of electronic stethoscopes for cardiac auscultation.
There are several electronic stethoscopes available on the market today, with a very high potential for healthcare namely telemedicine, assisted decision and education. However, there are no recent comparatives studies published about the recording quality of auscultation sounds. In this study we aim to: a) define a ranking, according to experts opinion of 6 of the most relevant electronic stethoscopes on the market today; b) verify if there are any relations between a stethoscope's performance and the type of pathology present; c) analyze if some pathologies are more easily identified than others when using electronic auscultation. Our methodology consisted in creating two study groups: the first group included 18 cardiologists and cardiology house officers, acting as the gold standard of this work. The second included 30 medical students. Using a database of heart sounds recorded in real hospital environments, we applied questionnaires to observers from each group. The first group listened to 60 cardiac auscultations recorded by the 6 stethoscopes, and each one was asked to identify the pathological sound present: aortic stenosis, mitral regurgitation or normal. The second group was asked to choose, between two auscultation recordings, using as criteria the best sound quality for the identification of pathological sounds. Results include a total of 1080 evaluations, in which 72% of cases were correctly diagnosed. A detailed breakdown of these results is presented in this paper. As conclusions, results showed that the impact of the differences between stethoscopes is very small, given that we did not find statistically significant differences between all pairs of stethoscopes. Normal sounds showed to be easier to identify than pathological sounds, but we did not find differences between stethoscopes in this identification.


Relationship between serum Dickkopf-1 and albuminuria in patients with type 2 diabetes.
Diabetic kidney disease is a microvascular complication of diabetes with complex pathogenesis. Wingless signaling-mediated renal fibrosis is associated with diabetic kidney disease. Dickkopf-1, a negative regulator of Wingless, has been proven to participate in renal fibrosis, glucose metabolism, and inflammation. However, whether serum Dickkopf-1 levels are associated with diabetic kidney disease remains unclear. To assess the relationship between serum Dickkopf-1 levels and albuminuria in individuals with type 2 diabetes. Seventy-three type 2 diabetes patients and 24 healthy individuals were enrolled in this case-control study. Diabetic individuals were separated into normal albuminuria, microalbuminuria, and macroalbuminuria groups based on their urinary albumin/creatinine ratios (UACRs). Clinical characteristics and metabolic indices were recorded. Serum Dickkopf-1 levels were determined by enzyme-linked immunosorbent assay. No significant difference in serum Dickkopf-1 levels was found between healthy individuals and the normal albuminuria group. However, the levels in the microalbuminuria group were significantly lower than those in the normal albuminuria group (P = 0.017), and those in the macroalbuminuria group were the lowest. Bivariate analysis revealed that serum Dickkopf-1 levels were positively correlated with hemoglobin A1c level (r = 0.368, P < 0.01) and estimated glomerular filtration rate (r = 0.339, P < 0.01), but negatively correlated with diabetes duration (r = -0.231, P = 0.050), systolic blood pressure (r = -0.369, P = 0.001), serum creatinine level (r = -0.325, P < 0.01), and UACR (r = -0.459, P < 0.01). Multiple and logistic regression showed that serum Dickkopf-1 levels were independently associated with UACR (odds ratio = 0.627, P = 0.021). Serum Dickkopf-1 levels are negatively associated with UACR. Lower serum Dickkopf-1 levels could be a critical risk factor for albuminuria in diabetes.


Molecular Subtypes of Pulmonary Large-cell Neuroendocrine Carcinoma Predict Chemotherapy Treatment Outcome.
Purpose: Previous genomic studies have identified two mutually exclusive molecular subtypes of large-cell neuroendocrine carcinoma (LCNEC): the RB1 mutated (mostly comutated with TP53) and the RB1 wild-type groups. We assessed whether these subtypes have a predictive value on chemotherapy outcome.Experimental Design: Clinical data and tumor specimens were retrospectively obtained from the Netherlands Cancer Registry and Pathology Registry. Panel-consensus pathology revision confirmed the diagnosis of LCNEC in 148 of 232 cases. Next-generation sequencing (NGS) for TP53, RB1, STK11, and KEAP1 genes, as well as IHC for RB1 and P16 was performed on 79 and 109 cases, respectively, and correlated with overall survival (OS) and progression-free survival (PFS), stratifying for non-small cell lung cancer type chemotherapy including platinum + gemcitabine or taxanes (NSCLC-GEM/TAX) and platinum-etoposide (SCLC-PE).Results:RB1 mutation and protein loss were detected in 47% (n = 37) and 72% (n = 78) of the cases, respectively. Patients with RB1 wild-type LCNEC treated with NSCLC-GEM/TAX had a significantly longer OS [9.6; 95% confidence interval (CI), 7.7-11.6 months] than those treated with SCLC-PE [5.8 (5.5-6.1); P = 0.026]. Similar results were obtained for patients expressing RB1 in their tumors (P = 0.001). RB1 staining or P16 loss showed similar results. The same outcome for chemotherapy treatment was observed in LCNEC tumors harboring an RB1 mutation or lost RB1 protein.Conclusions: Patients with LCNEC tumors that carry a wild-type RB1 gene or express the RB1 protein do better with NSCLC-GEM/TAX treatment than with SCLC-PE chemotherapy. However, no difference was observed for RB1 mutated or with lost protein expression. Clin Cancer Res; 24(1); 33-42. ©2017 AACR.


An overview of candesartan in clinical practice.
Hypertension is a major risk factor for coronary heart disease, stroke, heart failure and renal disease. The Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure 7 defined hypertension as a blood pressure of more than 140/90 mmHg and recommended to initiate treatment with a two-drug combination for stage 2 hypertension (blood pressure of 160-179/100-109 mmHg). The need for drug combinations is clear from a patient and physician perspective as they provide more effective blood pressure lowering, reduce pill burden, improve compliance and decrease hypertension-related morbidity and mortality. Angiotensin II receptor blocker therapy has been proven to be well tolerated and effective in the management of hypertension, chronic heart failure with left ventricular dysfunction and the prevention and progression of diabetic renal disease. Blockers of the renin-angiotensin system are an important component of antihypertensive combination therapy. Thiazide-type diuretics are usually added to increase the blood pressure lowering efficacy. Fixed drug-drug combinations of both principles, such as candesartan/hydrochlorothiazide, are highly effective in lowering blood pressure while providing improved compliance, a good tolerability and largely neutral metabolic profile. In this article, we review the literature for the role of candesartan-based therapy for hypertension, stroke, diabetes mellitus and heart failure.


Long survival with giant cell myocarditis.
Several aspects of giant cell myocarditis remain controversial, including the natural history of the disease and the nature of the giant cells. We have observed three patients who had long survival with chronic active giant cell myocarditis. The first patient was a 59-yr-old female who had a 10-yr history of complete heart block which was found at autopsy to have been caused by giant cell myocarditis. The second patient is a 36-yr-old female who received a heart transplant 5 yr after a biopsy proven episode of active myocarditis, and examination of the explanted heart revealed giant cell myocarditis. The third patient was a 41-yr-old male who received a heart transplant 2 yr after developing progressive heart failure, and the explanted heart had giant cell myocarditis. On immunohistochemical study of the three hearts, the giant cells stained with the macrophage markers lysozyme and KP-1 (CD-68). Staining of the same cells with desmin and actin was focally positive in a punctate pattern, correlating with the ultrastructural presence of myofibrils within giant cell phagolysosomes. The associated lymphocytic infiltrate stained primarily for the T-cell markers CD-3, CD-45RO, and CD-43 whereas only a few of the lymphocytes stained with the B-cell marker CD-20. The long histories of cardiac dysfunction in the three patients show that giant cell myocarditis may have a protracted course. The morphologic studies show that the giant cells are of histiocytic origin but can contain phagocytosed components of myocytes, observations that may account for the controversy surrounding the nature of the giant cells in giant cell myocarditis.


Volume-associated osmolyte fluxes in cell lines with or without the anion exchanger.
To investigate the involvement of a red cell-type anion exchanger in the volume-sensitive amino acid release, the hyposmolarity-evoked release of D-[3H]aspartate and [3H]taurine was examined in three cell lines: 1) wild-type Chinese hamster ovary (CHO-K1) cells, expressing an anion exchanger activity (Cl-/SO4(2-)) functionally similar to the erythroid band 3; 2) a mutant CHO cell type (CHO 605) lacking this anion exchanger activity; and 3) 293 cells in which the Cl-/HCO3(-) anion exchanger is absent. All cell types accumulated D-[3H]aspartate and [3H]taurine under isosmotic conditions, and, similarly, in the three cell lines, cell swelling evoked by hyposmolarity induced a rapid and transient increase in the amino acid efflux. Blockers of the anion exchanger and/or Cl- channels [niflumic acid, dipyridamole, diphenylamine-2-carboxylate,5-nitro-2-(3-phenylpropylamino)-benzoi c acid, and 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid] were potent inhibitors of amino acid efflux in the three cell lines. 125I- efflux, used as a marker for Cl- fluxes, was also markedly increased in response to cell swelling in all cell lines, and this efflux was inhibited by the anion exchanger/Cl- channel blockers. These results do not support a role for an anion exchanger in the hyposmolarity-induced amino acid efflux and suggest that amino acids and Cl- may be transported by the same or a similar mechanism, presumably an anion channel-like structure.


Psychiatric syndromes related to antiepileptic drugs.
All antiepileptic drugs may provoke positive or negative psychiatric reactions in individual patients. These psychotropic effects are not simply idiosyncratic but depend on the drug's anticonvulsive strength and the person's genetic and biographic psychiatric predisposition. Mechanisms related to psychiatric adverse events are polytherapy and folate deficiency, forced normalization, drug toxicity, and withdrawal. Our knowledge on dose independent, idiosyncratic psychotropic side effects is still limited. With respect to the older antiepileptic drugs there are almost no systematic data, and knowledge is largely empirical and based on anecdotal reports. With respect to the new generation of anticonvulsants there are data on psychiatric side effects from drug trials. However, these data are not always entirely transparent to the interested epileptologist. Moreover, drug trials are designed to test anticonvulsive efficacy and psychiatric adverse events are not systematically reported, thus severity psychopathologic nature of behavioral problems remain obscure. Differences in patients included in trials do not allow comparisons of psychiatric risks of specific drugs, particularly since following the vigabatrin experience, patients with a psychiatric history were often excluded from trials. In this chapter, methodological issues related to data on psychiatric adverse events of AED are discussed followed by an overview on the current knowledge on psychiatric side effect profiles of old and new antiepileptic drugs.


New-onset atrial fibrillation: when is admission medically justified?
To determine 1) the percentage of patients with new-onset atrial fibrillation for whom admission is medically justified and 2) whether those patients for whom hospitalization is medically justified can be reliably identified in the ED. A retrospective, descriptive cohort analysis was performed using consecutive adult patients with new-onset atrial fibrillation seen in an urban, county hospital ED from 1987 through 1992. Admissions were categorized as medically justified if patients were hypotensive (systolic blood pressure < 90 mm Hg), had a diagnosis other than new-onset atrial fibrillation that warranted admission, or had a significant complication during the ED stay or during the subsequent hospitalization. The need for admission was considered to have been apparent during the ED evaluation if the patient fulfilled the above criteria for a medically justified admission while in the ED. Admission was medically justified for 143 of the 216 patients (66%; 95% CI 60-71%) admitted to our institution. For those patients whose admissions were medically justified, the most common concurrent conditions were congestive heart failure and chest pain suggestive of myocardial ischemia. The need for admission was apparent during the ED evaluation for 140 of the 143 patients (98%; 95% CI 94-100%) whose admissions were categorized as medically justified. Approximately one third of patients with new-onset atrial fibrillation may not require admission to the hospital. Most patients (98%) for whom admission is medically justified can be reliably identified during the ED evaluation.


Charge-shielding and the "paradoxical" stimulation of tubulin polymerization by guanidine hydrochloride.
Low concentrations of guanidine hydrochloride (GuHCl) increase the rate (and to a lesser degree, the extent) of tubulin polymerization as assessed by light scattering. Maximum enhancement occurs at 120-160 mM GuHCl followed by decreases at higher GuHCl. The latent period is decreased, and there is a 3-4 fold reduction in the critical concentration of polymerization. Electronmicrographs reveal microtubules in the controls and an increasing fraction of total polymers present as aberrant microtubules as the GuHCl concentration is increased from 20 to 100 mM. The GuHCl effect is markedly reduced, but not abolished, in tubulin S (in which the anionic C termini of both monomers have been removed). The GuHCl-induced polymerization has an absolute requirement for GTP and taxol or DMSO, is very sensitive to podophyllotoxin inhibition, and can overcome urea-mediated inhibition of polymerization. Guanidinium analogues mimic the GuHCl effect roughly as a function of the number of potential hydrogen bonds. The anions of the guanidine salts superimpose their inhibitory action on the guanidinium cation effect according to the lyotropic series. At higher GuHCl concentrations (peak effect 500-700 mM), a different polymer (type II) is formed that is GTP and taxol independent, but whose polymerization is retarded but not prevented by podophyllotoxin. Its structure resembles the fibrillar network seen in unfolding intermediates of other proteins. We conclude that both charge and hydrogen-bonding ability are major contributors to the GuHCl-induced promotion of tubulin polymerization, and that charge-shielding is likely to be the basis for this effect.


Analysis of genetic variability of Plasmodium vivax isolates from different Brazilian Amazon areas using tandem repeats.
Few genetic markers have been described to analyze populations of Plasmodium vivax. The genetic variability of P. vivax has been analyzed mainly among isolates taken from areas ranging from hyper- to holoendemic areas. These studies of genetic variability have neglected many areas with different epidemiologic profiles. The purpose of this study was to analyze the genetic variability of P. vivax isolates from four different Brazilian Amazon areas. We chose to study the five most polymorphic tandem repeats (TRs) identified so far. All TRs studied were polymorphic in at least one studied population, with a modal allele at nearly all loci. Expected heterozygosity ranged from 0.462 to 0.666 and did not correlate with the repeat array length. The genetic distances among the populations varied from 0.027 to 0.241, and did not correlate with their geographic separation. Tandem repeats identified in P. vivax isolates failed to allow geographic clustering.


Key ethical issues encountered in healthcare organizations: perceptions of nurse executives.
By the very nature of their daily work, nurse executives find themselves at the crossroads of the changing and challenging healthcare ethical environment in which clinical ethics and organizational ethics often collide. The authors present the findings of a survey of members of American Organization of Nurse Executives aimed at more clearly identifying the key ethical issues encountered in healthcare organizations by their nurse executives and others. Implications of the findings for healthcare organizations and their managers also are discussed briefly.


[Visual evoked potentials and ultrasonography in ischemic optic neuropathy].
To emphasize the importance of the examination VEP and Doppler ultrasonography for ION diagnostic establishment and their monitoring. There have been taken into VEP examination 43 patients, simple stimuli (flash) having used. For Doppler ultrasonography there have been taken into examination 38 patients whose extracerebral carotidian arterial system and ophthalmic artery have been examined. The VEP examination at the beginning of NOI have emphasized a depress of the amplitude of the VEP with normal VEP latency in 65.1% of cases and a depress of the amplitude with prolonged latency time in 4.7% of cases. VEP examination after 7-14 days from the ION beginning have emphasized only the depress of the amplitude in 48.8% of cases. Doppler ultrasonography examination have emphasized diffuse atherosclerotic lesions in 81.6% of cases and local carotidian stenosis in 7.9% of cases. VEP and Doppler ultrasonography examinations complete in an efficient way the range of clinical examinations and permit the getting of useful results in ION diagnosis. The examinations are complementary allowing the estimation of the nervous conductibility degree of deterioration and of the vascular pathway of the illness. VEP and Doppler ultrasonography are easy reproducible and non-aggressive methods which bring important diagnosis elements and allow ION monitoring.


Pentamethinium salts suppress key metastatic processes by regulating mitochondrial function and inhibiting dihydroorotate dehydrogenase respiration.
Mitochondria generate energy and building blocks required for cellular growth and function. The notion that mitochondria are not involved in the cancer growth has been challenged in recent years together with the emerging idea of mitochondria as a promising therapeutic target for oncologic diseases. Pentamethinium salts, cyan dyes with positively charged nitrogen on the benzothiazole or indole part of the molecule, were originally designed as mitochondrial probes. In this study, we show that pentamethinium salts have a strong effect on mitochondria, suppressing cancer cell proliferation and migration. This is likely linked to the strong inhibitory effect of the salts on dihydroorotate dehydrogenase (DHODH)-dependent respiration that has a key role in the de novo pyrimidine synthesis pathway. We also show that pentamethinium salts cause oxidative stress, redistribution of mitochondria, and a decrease in mitochondria mass. In conclusion, pentamethinium salts present novel anti-cancer agents worthy of further studies.


The prevalence of cardiac murmurs among standardbred racehorses presented with poor performance.
Seven hundreds fifty-two Standardbreds, with poor performance, underwent a thorough diagnostic protocol. In 157 out of 233 horses, with cardiac murmurs, echocardiography and color flow Doppler (CFD) mapping were performed. Murmur of tricuspid valve regurgitation was identified in 185 horses, while murmurs of mitral (23), aortic (9) and pulmonary (3) valve regurgitations were detected less frequently. Functional systolic, functional pre-systolic, and functional early diastolic murmurs were identified in 10, 11 and 2 horses. Two-dimensional and M-mode echocardiography showed no abnormality in 145 horses and by CFD the presence of one or more jets of valve regurgitation were observed in 149 patients. The results obtained suggest that cardiac murmurs are a common finding in Standardbreds presented with poor performance.


Wear assessment in bileaflet heart valves.
Sorin Biomedica has accumulated 20 years of experience in designing and manufacturing heart valves as well as in the development of turbostratic carbons, both as bulk coating (pyrolytic carbon, PyC) and as a thin film (Carbofilm). In designing a bileaflet valve, where hinges represent the most critical elements since wear occurs mainly at these points, we took into account: a) theoretical considerations on the geometry (flat-to-flat vs. curved-to-flat) of the coupling elements undergoing impact wear; b) kinematic coupling (sliding, rotation, rolling) between the moving parts in relation to friction wear; c) experimental wear rates of different material couples (PyC/PyC, metal/PyC) assessed by paying attention to test artifacts due to particle contamination; and d) wear mechanisms involving brittle fracture mechanics for bulk PyC and ductile fracture mode for metals. On the basis of the above evaluations a Carbofilm coated titanium alloy housing and PyC leaflets were developed for the Sorin Bicarbon valve. A flat-to-flat coupling between hinge stops and mating pivot surfaces for reducing the impact wear and a rolling action aimed at minimizing the friction wear were designed for the hinge. The Bicarbon long term durability has been assessed by accelerated wear tests conducted in comparison with clinically accepted bileaflet prostheses (CarboMedics and St. Jude Medical). The main results for the Bicarbon valve were, wear rates slightly lower or comparable to those found in the reference valves and wear morphology free from microfractures, while deep cracks associated with higher stress concentrations were detected on the PyC components of the reference valves. No mechanical failure or loss of functionality occurred up to 2,100 million cycles (equivalent of 52.5 years).


Clinicopathological Features and Survival Data of Localized Renal Masses in Young Adults
Purpose: Renal tumors are rarely seen in young adults. In this study, was aimed to report the data of 18-40 years old patients with Renal Cell Carcinoma (RCC) whom we operated. Material and Method: We retrospectively reviewed the data of patients between the ages of 18 and 40 years old patients who have renal masses. All patients were evaluated with chest X-ray, Computed tomography (CT) and/or MRI. Radical or partial nephrectomy was performed for clinical localized masses with malignancy suspicion. Clinicopathological features and survival data of all the patients were recorded. In the follow-up protocol routine blood tests, chest X-ray and abdominal CT were used. Results: A total of 42 patients, [22 (52.4%) male and 20 (47.6%) female], with a mean age of 34.48 (range 18 to 40) were included in the study. Of these, 32 (%76) had RCC and 10 (24%) had benign pathologies. Female patients had more benign pathology (35% vs 13.6%). The most commonly subtype of RCC (n = 22% 69) was clear cell RCC (cRCC), while the most common benign mass was oncocytoma (n = 4% 40). At the mean follow-up period of 42.34 months, overall survival rate was found to be 93.8%. Conclusion: Young adults with localized renal mass have benign pathology in a considerable rate. All of the malign masses in this population have low Furhman grade (1 or 2).


The HIF-1α antisense long non-coding RNA drives a positive feedback loop of HIF-1α mediated transactivation and glycolysis.
Hypoxia-inducible factor-1 (HIF-1) is a master driver of glucose metabolism in cancer cells. Here, we demonstrate that a HIF-1α anti-sense lncRNA, HIFAL, is essential for maintaining and enhancing HIF-1α-mediated transactivation and glycolysis. Mechanistically, HIFAL recruits prolyl hydroxylase 3 (PHD3) to pyruvate kinase 2 (PKM2) to induce its prolyl hydroxylation and introduces the PKM2/PHD3 complex into the nucleus via binding with heterogeneous nuclear ribonucleoprotein F (hnRNPF) to enhance HIF-1α transactivation. Reciprocally, HIF-1α induces HIFAL transcription, which forms a positive feed-forward loop to maintain the transactivation activity of HIF-1α. Clinically, high HIFAL expression is associated with aggressive breast cancer phenotype and poor patient outcome. Furthermore, HIFAL overexpression promotes tumor growth in vivo, while targeting both HIFAL and HIF-1α significantly reduces their effect on cancer growth. Overall, our results indicate a critical regulatory role of HIFAL in HIF-1α-driven transactivation and glycolysis, identifying HIFAL as a therapeutic target for cancer treatment.


Medical and psychological risk factors for incident hypertension in type 1 diabetic african-americans.
Objective. To determine risk factors for the development of hypertension among African-Americans living with type 1 diabetes. Methods. African-Americans with type 1 diabetes (n = 483) participated in a 6-year followup. At both baseline and followup blood pressure was measured twice in both sitting and standing positions using a standard protocol. Patients had a structured clinical interview, ocular examination, retinal photographs, and blood and urine assays and completed the Hostility and Direction of Hostility Questionnaire (HDHQ) and the Beck Depression Inventory (BDI). Results. Of the 280 diabetic patients with no hypertension at baseline, 82 (29.3%) subsequently developed hypertension over the 6-year followup. Baseline older age, longer duration of diabetes, family history of hypertension, greater mean arterial blood pressure, overt proteinuria, increasing retinopathy severity, peripheral neuropathy, smoking, and higher hostility scores were significantly associated with the development of hypertension. Multivariate analyses showed that higher hostility scores and overt proteinuria were significantly and independently associated with the development of hypertension in this population. Conclusions. The development of hypertension in African-Americans living with type 1 diabetes appears to be multifactorial and includes both medical (overt proteinuria) as well as psychological (high hostility) risk factors.


Endocarditis due to Gemella haemolysans in a newly diagnosed multiple myeloma patient.
An 87-year-old Caucasian woman with hypertension, diabetes mellitus type 2, and COPD was admitted with 1-week duration of back pain and weight gain. The physical examination revealed jugular venous distention, rales in the left lower lung field, and severe pitting edema over lower extremities. As workup for leukocytosis, blood cultures grew Gemella haemolysans. Subsequently, a transthoracic echocardiogram revealed vegetation on the non-coronary aortic leaflet and mild aortic stenosis. She was treated with ampicillin and gentamicin. After further investigation, the patient was diagnosed with plasma cell myeloma, the monoclonal lambda type. This is the first reported case of G. haemolysans endocarditis in a multiple myeloma patient.


Acute dose of alcohol affects cognitive components of reaction time to an omitted stimulus: differences among sensory systems.
The possibility that moderate blood alcohol concentrations (BACs) may impair cognitive processes before disturbing motor functions has raised concern about the safety of BACs <or=80 mg/100 ml. Reaction time (RT) to the presentation of a stimulus or to the omission of a regularly occurring stimulus has been fractionated into independent premotor (cognitive) and motor (movement) components. It has been suggested that cognitive processes may be impaired at lower BACs than are motor processes, but the effects of moderate rising and declining BACs on these component RT measures have not been investigated. An omitted stimulus RT task was used to test the hypothesis that moderate rising BACs impair (slow) premotor RT (PMRT) when motor RT (MRT) remains unaffected. The task included visual, auditory, and tactile stimuli to explore differences in sensory sensitivity to alcohol. Thirty male social drinkers were randomly assigned to three groups (n=10) that received 0.62 g/kg alcohol, 0.8 g/kg alcohol, or a placebo (0 g/kg). All participants performed the task three times: baseline and during rising and declining BACs. Comparisons of the alcohol and placebo groups showed rising BACs slowed PMRT and had no detectable effect on MRT. Impairment in visual PMRT occurred under both alcohol doses. Auditory PMRT was impaired only under the 0.8 g/kg dose, and tactile PMRT was unaffected. Cognitive functions are impaired by moderate increasing BACs that do not affect motor movement, and the tactile sensory system may be relatively insensitive to this impairment.


Chinese nurse stress in Taiwan, Republic of China.
An exploratory study was conducted to understand the Chinese nurses' perceptions of their work stress in Taiwan, Republic of China (ROC). Data were based on the written answers to two open-ended questions from the randomly selected Chinese nurses working at 3 of the 10 first-ranked teaching hospitals that had 900-2,000 hospital beds. The findings showed that stressors in work situations for Chinese nurses were similar to those of their Western colleagues in four categories: nursing care related to patient condition, interpersonal relationships, workload, and opportunity for promotion. In addition, the Chinese respondents especially identified pressure in the role of a unit educator as stressful. Any troubled interpersonal relationship of the Chinese nurse may have been experienced as a greater source of pressure than nurses in other cultures. It is suggested that there might be some similar stressors in the nurse work situation when comparing the Chinese nurse working in the modern hospital in Taiwan to the nurses in large hospitals in the Western culture. Yet the difference between these nurses was the greater emphasis the Chinese nurses placed on the value of advanced study and interpersonal harmony.


Magnitude of Gonial Angle Influence on the Commonness of Mandibular Angle Fractures.
The aim of the study was to review the literature on the influence of gonial angle on mandibular angle fracture. The present systematic review addresses the following focus question: Does the magnitude of gonial angle influence the incidence of mandibular angle fractures? Electronic and manual literature searches were conducted on databases: PubMed/MEDLINE, Embase, Science direct, the Cochrane Library, and clinicaltrials.gov for studies published up to August 2019 to collect information about the effect of gonial angle, a skeletal morphological parameter with an incidence of fracture of the angle of the mandibular arch. Systematic literature review was performed to identify studies evaluating the effect of gonial angle in patients suffering from mandible fractures. Large retrospective studies were included and case reports were excluded. Fifteen hundred articles published before August 2019 were identified. One hundred and sixteen articles met the inclusion criteria. Two articles remained when exclusion criteria were applied. As measured in the two included studies containing 280 panoramic radiographs of mandibular fractures, the mean gonial angle of patients in the angle fracture group ranged from 126.8° ± 7.9° to 128.5° ± 5.4°. The mean gonial angle of patients in the nonangle fracture group ranged from 118.5° ± 4.4° to 122.3° ± 4.9°. The mean gonial angle of patients in the angle fracture group displayed a range from 118.9° to 134.7° (confidence interval [CI] 95% 5.89-8.05), whereas the mean gonial angle of patients in nonangle fracture group displayed a range from 114.1° to 127.2° (CI 95% 3.89-4.95). A high gonial angle is an important factor influencing the occurrence of mandibular angle fractures owing to the poorer quality of bone and reduced height at the ramus angle region, all of which necessitate a modification of osteosynthesis techniques.


Risk factors and chronic conditions among Aboriginal and non-Aboriginal populations.
In Canada, the prevalence of behavioural risk factors and chronic conditions differs for Aboriginal and non-Aboriginal populations, but little research has examined changes over time. This study compares several major risk factors and chronic conditions in Aboriginal and non-Aboriginal populations not living on reserves in the North (Yukon, Northwest Territories, Nunavut) and in southern Canada at two time points. The data are from cycle 1.1 (2000/2001) and cycle 3.1 (2005/2006) of the Canadian Community Health Survey: 115,990 respondents aged 20 or older, and 118,716 respondents, respectively. Overall, 3.8% of respondents reported Aboriginal cultural or racial background. Crude prevalence estimates, adjusted odds ratios, and bootstrap-derived confidence intervals were calculated for seven risk factors and nine chronic conditions at each time point. In 2000/2001, Aboriginal people in the North were more likely than those in southern Canada to be obese, smoke daily and have infrequent physical activity, but less likely report a number of chronic conditions. Between 2000/2001 and 2005/2006, the odds of reporting risk factors increased among Aboriginal people in the North, and differences in the prevalence of chronic diseases were less pronounced. Few differences between non-Aboriginal respondents in the North and in southern Canada were observed. Compared with southern Canada, the profile of health is changing more rapidly for Aboriginal than non-Aboriginal populations in the North, and appears to be worsening for the former.


Perceptions of IBD within patient and community samples: a systematic review.
Objective: Inflammatory bowel disease (IBD) is a chronic, gastrointestinal condition that involves a range of debilitating bowel symptoms. Adjustment to living with IBD can be negatively impacted by maladaptive cognitive and behavioural factors (e.g. negative illness representations and repressing emotions). Patient samples also report negative reactions from the general public and such perceptions can further negatively impact people living with IBD. Therefore, we aimed to systematically review literature investigating the illness perceptions, perceived stigmatisation, and negative emotional reactions toward IBD within patient and community samples. We also aimed to review how these factors impact those living with IBD (i.e. adjustment, psychological health). Design: A range of databases (e.g. Psych INFO, PubMed) were searched over two years. One reviewer individually screened titles and abstracts using the specified inclusion criteria, and this process was repeated by a second reviewer. Subsequently, the full text articles were screened and data were extracted for the 82 articles that satisfied the inclusion criteria. Following data extraction, a narrative synthesis was conducted.Results: The review of 82 studies suggested that negative illness perceptions are linked to poorer psychosocial outcomes, that patient samples frequently anticipate stigmatisation, fear relating to bowel accidents was the most common emotion reported, and that the general public direct little enacted stigma towards IBD.Conclusion: For people living with IBD: (i) poorer psychological adjustment was reported by those who held more negative perceptions and reactions toward their illness; and (ii) their concerns regarding public perceptions of IBD warrants further empirical attention. Results emphasise the importance of targeting perceptions, and facilitating education and adaptive responding during treatment.


What's hot in animal biosafety?
In recent years, the emergence or re-emergence of critical issues in infectious disease and public health has presented new challenges and opportunities for laboratory animal care professionals. The re-emergence of bioterrorism as a threat activity of individuals or small groups has caused a heightened awareness of biosecurity and improved biosafety. The need for animal work involving high-risk or high-consequence pathogens and for arthropod-borne diseases has stimulated renewed interest in animal biosafety matters, particularly for work in containment. Application of these principles to animals retained in outdoor environments has been a consequence of disease eradication programs. The anticipated global eradication of wild poliovirus has prompted the promulgation of new biosafety guidelines for future laboratory and animal work. Increased concern regarding the use of biologically derived toxins and hazardous chemicals has stimulated a new categorization of facility containment based on risk assessment. Recognition that prion disease agents and other high-consequence pathogens require safe handling and thorough destruction during terminal decontamination treatment has led to the development of new biosafety guidelines and technologies. The implementation of these guidelines and technologies will promote state-of-the-art research while minimizing risk to laboratory animals, researchers, and the environment.


The complete mitochondrial genome of the Downy woodpecker, Picoides pubescens (Piciformes: Picidae).
The Downy woodpecker (Picoides pubescens) is a species of woodpecker which is the smallest in North America. This present study firstly reported the complete mitochondrial genome of downy woodpecker. We performed assembly of mitogenome structural by SPAdes and the Picidae species Dryocopus pileatus act as a reference. The mitogenome was 16 840 bp in length, which contains 13 protein-coding genes, 22 transfer RNAs, 2 ribosomal RNAs and 1 putative misc-feature region. The overall AT content is 52.76% which is higher than GC. To approve the accuracy of new determined mitogenome sequences, a phylogenetic tree of downy woodpecker together with other nine closely species was established by 12 protein-coding genes. This first complete mitogenome of Picoides species will contribute to identify species and study the related evolution events.


On the clinical significance of acquired antithrombin deficiency.
The concentration of antithrombin III (AT) was determined with a chromogenic method in plasma samples from 1,302 patients referred for evaluation of the haemostatic system. A clearly subnormal AT level (below 60%) was found in 129 patients. In ten cases, this was explained by known (8 cases) or suspected (2 newborns) hereditary deficiency. Only in 5% of the 600 cases referred with definite or suspected thrombosis, AT was below 60%. These cases had a lethality of about 20%. In about 30% of the cases with liver disease, AT was below 60%. In a group of 72 patients with either severe infection, cardiac insufficiency, malignancy or suspected DIC for other reasons, AT was below 60%. Also in this group lethality was about 50% despite lack of a clear DIC blood profile in 67 of the 72 patients. The results indicate that an AT value below 60% of normal, unexplained by hereditary deficiency, carries a grave prognosis.


Laminopathies.
Nuclear lamins form a fibrous nucleoskeletal network of intermediate-sized filaments that underlies the inner nuclear membrane. It associates with this membrane through interactions with specific integral nuclear membrane proteins, while within this flattened lamin lattice the nuclear pore complexes are embedded. Next to this peripheral network, the lamins can form intranuclear structures. The lamins are the evolutionary progenitors of the cytoplasmic intermediate filament proteins and have profound influences on nuclear structure and function. These influences require that lamins have dynamic properties and dual identities as structural building blocks on the one hand, and transcription regulators on the other. Which of these identities underlies the laminopathies, a myriad of genetic diseases caused by mutations in lamins or lamin-associated proteins, is a topic of intense debate.


Oxygen concentrators.
This study focuses on molecular-sieve concentrators that deliver high-content oxygen for continuous, long-term therapy, which improves and extends the quality of life for adult patients who suffer from such illnesses as chronic obstructive pulmonary disease. We did not include membrane concentrators, which produce a maximum concentration of 40% oxygen (compared with 90% or more for molecular-sieve concentrators), because they are not suitable for most long-term oxygen-therapy applications. Although oxygen concentrators are most often used at home, they are also occasionally used in hospitals or nursing homes as an economical method of delivering oxygen when built-in systems are not required or available. We evaluated 10 oxygen concentrators from nine manufacturers. All of the units are similar in general design and appearance, except for one 3 L/min capacity unit that is smaller and lighter than the other 4 or 5 L/min units. Our ratings and rankings are based primarily on the availability of an oxygen concentrator status indicator that meets our criteria, as well as on electrical safety and maintenance issues. Nine units are rated Acceptable; one unit is rated Conditionally Acceptable because it poses an electrical safety hazard. Readers are cautioned not to base purchasing decisions on our ratings alone, but on a thorough understanding of all issues surrounding the use of oxygen concentrators, which can be gained only by reading this study in its entirety. In the Discussion section, "Issues in Selecting, Purchasing, and Using Oxygen Concentrators," we discuss important factors to consider, such as required flow, oxygen concentration status indicators, high-temperature performance, electrical safety, noise, maintenance, and cost. Manufacturers' specifications for these and other units are available in ECRI's Hospital Product Comparison System.


Herniation of the lumbar intervertebral disk in teenagers.
Thirty-five teenagers treated for herniation of the lumbar intervertebral disk are reviewed. In almost all cases the subjective symptoms were very minor compared to the physical signs. Radiologic examination revealed a high incidence of lumbosacral anomalies and, less frequently, anomalies of the dural sac or nerve roots. Conservative treatment failed to improve the symptoms in all cases, while surgery and various closed techniques (chemonucleolysis, percutaneous diskectomy) were successful.


The Weekend Effect in Carotid Endarterectomy for Symptomatic Carotid Stenosis.
BackgroundRecent studies report a limited window in which carotid endarterectomy (CEA) provides the greatest benefit for symptomatic carotid stenosis. Given the time-sensitive nature of CEA for symptomatic stenosis, it is important to understand whether patient outcomes are adversely affected by undergoing CEA over the weekend. Currently, it is unclear whether CEA is impacted by the "weekend effect" phenomenon. Methods A multi-institutional database was queried for all patients undergoing CEA for symptomatic carotid artery stenosis from 2015 to 2020 via ICD-9 codes. A total of 288 patients were identified during the study period. Univariate and multivariate analysis were used to compare outcomes based on weekend vs weekday surgery. Results A total of 261 patients (90.6%) underwent weekday CEA, as compared to 27 (9.4%) on the weekend. There were no differences in age, race, gender, or medical comorbidities between groups. Primary surgeon specialty was predominantly vascular surgery (77.0% weekday and 74.1% weekend) followed by neurosurgery (19.9% weekday and 25.9% weekend). Operative time was similar between groups (3.1 (weekday) vs 2.9 hr (weekend), P = .33) as well as estimated blood loss (100 vs 100 mL, P = .54). Hospital length of stay did not differ between groups (P = .69). Combined stroke and 30-day mortality rate was 2.0% on weekdays, compared to 3.7% on weekends (P = .75). On multivariate analysis, weekend surgery was not predictive of postoperative stroke or 30-day mortality (odds ratio .11 [95% CI: -1.57 to 1.85], P = .90). Conclusion In our multi-institutional experience, we did not identify a "weekend effect" in patients undergoing CEA for symptomatic carotid artery stenosis. Surgical revascularization should not be withheld on account of a weekend procedure in similar academic medical centers.


Delivery strategies for novel vaccine formulations.
A major challenge in vaccine design is to identify antigen presentation and delivery systems capable of rapidly stimulating both the humoral and cellular components of the immune system to elicit a strong and sustained immunity against different viral isolates. Approaches to achieve this end involve live attenuated and inactivated virions, viral vectors, DNA, and protein subunits. This review reports the state of current antigen delivery, and focuses on two innovative systems recently established at our labs. These systems are the filamentous bacteriophage fd and an icosahedral scaffold formed by the acyltransferase component (E2 protein) of the pyruvate dehydrogenase complex of Bacillus stearothermophilus.


[Gansu population growth].
Gansu Province scored achievements in birth control in 1980. The population growth rate declined from 10.8/1000 in 1979 to 8.9/1000.


Contributions of the different extramembranous domains of the mechanosensitive ion channel MscL to its response to membrane tension.
MscL is a mechanosensitive channel that is gated by tension in the membrane bilayer alone. It is a homo-oligomer of a protein comprising two transmembrane segments connected by an external loop, with the NH(2) and COOH termini located in the cytoplasm. The contributions of the extramembranous domains of the channel to its activity were investigated by specific proteolysis during patch-clamp experiments. Limited proteolysis of the COOH terminus or the NH(2) terminus increased the mechanosensitivity of the channel without changing its conductance. Strikingly, after cleavage of the external loop of each monomer, the channel was still functional, and its mechanosensitivity was increased dramatically, indicating that the loop acts as a spring that resists the opening of the channel and promotes its closure when it is open. These results indicate that the integrity of most of the extramembranous domains is not essential for mechanosensitivity. They suggest that these domains counteract the movement of the transmembrane helices to which they are connected, thus setting the level of sensitivity of the channel to tension.


Clustering and phases of compartmentalized granular gases.
This paper experimentally investigates the clustering conditions for compartmentalized monodisperse granular gases, determining the critical particle number and condensation granular temperature at the gas-clustering transition. When one heavier intruding particle is added to a monodisperse gas, it is found that the condensation temperature decreases with the ratio of the mass of the intruding particle to that of the background particle. This phenomenon can be mathematically characterized by a proposed linear relation, which is reminiscent of a relation between the freezing point depression for a solvent and the concentration of an added solute. Finally we perform various tests by changing the numbers of two types of particles in bidisperse granular mixtures to construct the phase diagrams, which present the range of the five different states, namely, homogeneous gas, unstable-gas, one-clustering, two-clustering, and granular oscillation states.


Self-triggered channel ion source.
An ion source made from a continuous dynode electron multiplier of the straight channel type and an ion reflector device is described. Its principle of operation is based on a continuous self-sustained ion and electron cascade in the multiplier channel. Operating characteristics and the analysis of the ions produced are presented. The intensity of the total ion current delivered (10(-9) to 10(-8) A) is enhanced by at least six orders of magnitude relatively to previously described similar devices. This source, as illustrated, may be used in gaseous mass spectrometry.


How much residual hearing is 'useful' for music perception with cochlear implants?
To compare performance on a song recognition task of bilaterally combined electric and acoustic hearing (bimodal stimulation) with electric or acoustic hearing alone. Subjects were 14 adults with cochlear implants (CI) who continued to use a hearing aid (HA) in one/both ears. Subjects were asked to identify excerpts from 15 popular songs, which were familiar to them, presented in a random order via a single loudspeaker. Presentation conditions were fixed in order: bimodal, CI alone and then HA alone. Musical excerpts were presented in each condition with and then without lyrics. In a subgroup of subjects (n = 8) with better low-frequency residual hearing (thresholds <85 dB hearing level (HL)), mean scores for bimodal stimulation were significantly greater than for CI alone. In addition, mean 'no lyrics' scores for HA alone (59.7%) were significantly greater than for CI alone (38.8%). All of these subjects considered bimodal stimulation to be the most enjoyable way to listen to music. For the remaining subjects (n = 6) there was no benefit from using bimodal stimulation over CI alone, and the majority of these preferred to listen to music using CI alone. Bimodal stimulation provides better perception of popular music, particularly melody recognition, compared to CI alone when low-frequency residual hearing is better than 85 dB HL.


Mental health service utilization review patterns in a Medicaid managed care program.
The current study investigated mental health utilization review (UR) clinical service authorization requests, denials, and reasons for denial in a statewide Medicaid managed care organization (MMCO) program. Retrospective analysis of utilization review data reported by MMCOs in New York State. Data from the utilization review practices of 15 MMCOs were collected and analyzed for calendar years 2017 and 2018. The data reported are specific to mental health services and include the number of authorization requests, number of clinical denials, and the reasons specified for each denial. Analyses were undertaken to determine the UR denial rates and most common reasons for denials. A total of 264,901 requests for inpatient mental health service authorizations and 53,687 requests for outpatient mental health service authorizations were made in 2017 and 2018. Of these, 1.5% of inpatient authorization requests and 0.4% of outpatient authorization requests were denied for reasons related to medical necessity. The most common reason for inpatient mental health service denials was that the patient no longer met the standard for the requested level of care. Low UR denial rates warrant further examination of the relationship between UR and both quality of care and patient outcomes in mental health care. With the substantial resources spent on UR, findings could point to areas of potential reforms to the system that may minimize these costs and improve care for patients with mental illness.


Bortezomib, thalidomide, dexamethasone induction therapy followed by melphalan, prednisolone, thalidomide consolidation therapy as a first line of treatment for patients with multiple myeloma who are non-transplant candidates: results of the Korean Multiple Myeloma Working Party (KMMWP).
Bortezomib (VELCADE), thalidomide and dexamethasone (VTD), as well as melphalan, prednisolone, and thalidomide (MPT) therapy, are highly effective in patients with multiple myeloma. We evaluated the responses and survival times of 35 patients treated with VTD followed by MPT. All patients were newly diagnosed and non-transplantation candidates. Patients received six cycles of VTD, which were followed by eight cycles of MPT. Approximately 97% of patients exhibited early responses to therapy, as early as the second cycle of VTD. Thirty percent of the responses were high quality, which was defined as a complete response (CR), a near-CR or a very good partial response. High-risk patients were defined as patients with any of the following aberrations: del(13), t(4;14), or del(17p). The remaining patients were defined as standard risk. Eleven high-risk patients showed 100% response rates, including 91% high-quality responses. In contrast, 13 standard-risk patients exhibited 92% response rates, including 61% high-quality responses. The overall 2-year survival rates were 60% in high-risk patients and 85% in standard-risk patients, which was not significantly different. As a first-line therapy, VTD followed by MPT has the potential to provide high-quality responses with durable remission among elderly and high-risk patients (clinicaltrials.gov identifier: NCT00320476).


Peripherally Modified Tetraphenylethene: Emerging as a Room-Temperature Luminescent Disc-Like Nematic Liquid Crystal.
A blue-light-emitting liquid crystalline (LC) material was designed and prepared. By employing a twisted luminescent core (i.e., tetraphenylethene), four peripheral LC units with long alkyl chains and the small polar benzyl-ether-typed linking groups, the resulting material displayed a hexagonal columnar phase near room temperature and a disc-like nematic phase between 32 and 70 °C. The columnar LC showed a high quantum yield of 0.49 at 20 °C, and the efficient luminescence property was retained even in the isotropic phase at high temperature. Additionally, the fluidity of the nematic phase rendered the LC a non-volatile solvent, and the proper addition of a red dye led to the achievement of polarized white-light emission, which revealed a promising application prospect in LC display fabrication.


Using pyridine amidoximes in 3d-metal cluster chemistry: a novel ferromagnetic Ni12 complex from the use of pyridine-2-amidoxime.
The use of pyridine-2-amidoxime in reaction with NiCl2.6H2O in the presence of NaOMe has led to a cationic NiII 12 cluster with novel structural features; each cluster molecule is a ferromagnet with a spin ground state of S = 6 arising from ferromagnetic exchange between the six octahedral NiII ions, but with intercationic interactions also affecting the magnetic properties.


Mutational analysis of the defective protease in classic late-infantile neuronal ceroid lipofuscinosis, a neurodegenerative lysosomal storage disorder.
The late-infantile form of neuronal ceroid lipofuscinosis (LINCL) is a progressive and ultimately fatal neurodegenerative disease of childhood. The defective gene in this hereditary disorder, CLN2, encodes a recently identified lysosomal pepstatin-insensitive acid protease. To better understand the molecular pathology of LINCL, we conducted a genetic survey of CLN2 in 74 LINCL families. In 14 patients, CLN2 protease activities were normal and no mutations were identified, suggesting other forms of NCL. Both pathogenic alleles were identified in 57 of the other 60 LINCL families studied. In total, 24 mutations were associated with LINCL, comprising six splice-junction mutations, 11 missense mutations, 3 nonsense mutations, 3 small deletions, and 1 single-nucleotide insertion. Two mutations were particularly common: an intronic G-->C transversion in the invariant AG of a 3' splice junction, found in 38 of 115 alleles, and a C-->T transition in 32 of 115 alleles, which prematurely terminates translation at amino acid 208 of 563. An Arg-->His substitution was identified, which was associated with a late age at onset and protracted clinical phenotype, in a number of other patients originally diagnosed with juvenile NCL.


Study of neurovascular coupling during cold pressor test in patients with migraine.
Altered neurovascular coupling in migraineurs could be a consequence of impaired function of modulatory brainstem nuclei. The cold pressor test (CPT) should activate brainstem structures. We measured visually evoked cerebral blood flow velocity response (VEFR) to CPT in migraine. Twenty-three healthy volunteers and 29 migraineurs participated in the study. We measured arterial blood pressure, end-tidal CO2, heart rate and cerebral blood flow velocity in posterior and middle cerebral artery using transcranial Doppler. VEFR was calculated as cerebrovascular reactivity to photic stimulation before, during and after CPT. In healthy individuals, there was a significant decrease in peak systolic VEFR from CPT phase to recovery phase (p < 0.05). There was an increase in mean VEFR from basal to CPT phase and a decrease from CPT to recovery phase, both significant (p < 0.05). End-diastolic VEFR increased from basal to CPT phase and decreased in recovery phase below the basal phase values, all changes significant (p < 0.05). In migraine, no statistically significant changes in peak systolic, mean or end-diastolic VEFRs were observed between phases (p > 0.05). The differences in phases in mean and end-diastolic VEFRs between the basal phase and the CPT phase and between the CPT phase and the recovery phase were significantly higher in healthy individuals (p < 0.05). The absence of the effect of CPT on VEFR in migraine is likely to be a consequence of impaired subcortical modulation of neurovascular coupling.


Evolution of water recycling in Australian cities since 2003.
The prolonged Australian drought which commenced in 2002, and the agreement between Australia's Commonwealth and States/Territories governments to progress water reform through the National Water Initiative, has resulted in many new recycling projects in Australia's capital cities. Dual reticulation systems are being advanced in new subdivision developments in Sydney, Melbourne and Adelaide. Brisbane has installed three large Advanced Water Treatment Plants that are designed to send indirect potable recycled water to the Wivenhoe Dam which is Brisbane's principal water reservoir. Numerous water recycling projects are serving industry and agriculture. Experimental managed aquifer recharge is being undertaken with wetland-treated stormwater in Adelaide and reverse osmosis treated wastewater in Perth. New National Water Quality Management Strategy recycled water guidelines have been developed for managing environmental risks, for augmentation of drinking water supplies, for managed aquifer recharge and for stormwater harvesting and reuse. Many recent investments are part-supported through Commonwealth government grants. Desalination plants are being established in Melbourne and Adelaide and a second one in Perth in addition to the newly-operational plants in Perth, South-East Queensland and Sydney. Despite there being numerous examples of unplanned indirect potable recycling, most governments remain reluctant about moving towards planned potable recycling. There is evidence of some policy bans still being maintained by governments but the National Water Commission continues to reinforce the necessity of an even-handed objective consideration of all water supply options.


Individual Survival Expectations and Actual Mortality: Evidence from Dutch Survey and Administrative Data.
Because of the important role that survival expectations play in individual decision making, we investigate the extent to which individual responses to survival probability questions are informative about actual mortality. In contrast to earlier studies, which relied on the Health and Retirement Study (HRS) of US individuals aged 50 and over, we combine household survey data on subjective survival probabilities with administrative data on actual mortality for Dutch respondents aged 25 and over. Our main finding is that in our sample, individual life expectancies (measured as subjective survival probabilities) do predict actual mortality even when we control for a large set of health indicators. Our results further suggest that, on average, women underestimate their remaining life duration, whereas men tend to predict their survival chances more realistically. Both sexes, however, tend to overestimate the age gradient in mortality risk and underestimate the health risks of smoking.


First report of Cherry virus F infecting Japanese plum in Korea.
Cherry virus F (CVF) is a tentative member of the genus Fabavirus in the family Secoviridae, consisting of two RNA segments (Koloniuk et al. 2018). To date, CVF has been documented in only sweet cherry (Prunus avium) in the Czech Republic (Koloniuk et al. 2018), Canada, and Greece. In May 2014, we collected leaf samples from four symptomatic (leaf spots and dapple fruits) and two asymptomatic Japanese plum cultivars (Sun and Gadam) grown in an orchard in Hoengseong, South Korea, to identify viruses and viroids infecting plum trees. Total RNA from individual plum trees was extracted using two commercial kits: Fruit-mate for RNA Purification Kit (Takara, Shiga, Japan) and RNeasy Plant Mini Kit (Qiagen, Hilden, Germany). We generated six mRNA libraries from the six different plum cultivars for RNA-sequencing using the TruSeq RNA Library Preparation Kit v2 (Illumina, CA, U.S.A.) as described previously (Jo et al. 2017). The mRNA libraries were paired-end (2 X 100 bp) sequenced with a HiSeq 2000 system (Macrogen, Seoul, Korea). The raw sequence reads were de novo assembled by Trinity program v. 2.8.6, with default parameters (Haas et al. 2013). The assembled contigs were subjected to BLASTX search against the non-redundant protein database in NCBI. Of the two asymptomatic cultivars, the transcriptome of asymptomatic plum cv. Gadam contained five contigs specific to CVF. Two and three contigs were specific to CVF RNA1 (2,571 reads, coverage 42.15%) and RNA2 (2,025 reads, coverage 53.04%), respectively. The size of these five contigs ranged from 241 to 5,986 bp. Contigs of 5,986 and 3,867 bp in length, referred to as CVF isolate Gadam RNA1 (GenBank MN896996) and RNA2 (GenBank MN896995), respectively, were subjected to BLASTP search against NCBI's non-redundant protein database. The results showed that the polyprotein sequences of RNA1 and RNA2 shared 95.3% and 93.11% amino acid identities with isolates SwC-H_1a from the Czech Republic (GenBank acc. no. AWB36326) and Stac-3B_c8 from Canada (AZZ10055), respectively. To confirm the infection of CVF in cv. Gadam, RT-PCR was conducted using CVF RNA1-specific primers designed based on the CVF reference genome sequences (MH998210 and MH998216), including 5'-CCACCAAATAGGCAAGAGGTCAC-3' (position 3190-3212) and 5'-CACAATCACCATCAATGGTCTCTGC-3' (position 3742-3766), and CVF RNA2-specific primers, including 5'-CTGCTTTATGATGCTAGACATCAAGATG-3' (position 1015-1042) and 5'-ACAATAGGCATGCTCATCTCAACCTC-3' (position 1594-1619). We amplified 577-bp RNA1-specific and 605-bp RNA2-specific amplicons that were cloned and then performed Sanger sequencing. Sequencing of the cloned amplicons for isolate Gadam RNA1 (GenBank MN896993) and RNA2 (GenBank MN896994) revealed values of 99.48% and 99.17% nucleotide identity to that of RNA1 and RNA2 determined by high-throughput sequencing, respectively. Additionally, we tested five plants for each of the six plum cultivars grown in the same orchard. The detection of CVF was carried out through PCR using the primers and protocol described above. Of the 30 trees, CVF was detected in three trees of cv. Gadam by both primer pairs. To our knowledge, this is the first report of CVF infecting Japanese plum and the first report of the virus in Korea. However, its prevalence in other Prunus species, including apricot, European plum, and peach, should be further elucidated.


Transcription in yeast activated by a putative amphipathic alpha helix linked to a DNA binding unit.
Gene activation by a DNA-binding regulatory protein in yeast requires the protein to have two components: one to recognize a specific DNA sequence and a second, the 'activating region', to interact with a general transcription factor or perhaps with RNA polymerase. The activating regions that have been characterized are acidic, and mutational analysis of one indicates that this acidity is important for activity. Here we report the design of an artificial protein bearing a novel 15-amino acid peptide linked to a DNA binding fragment of the yeast regulatory protein GAL4). The synthetic peptide is acidic and should it form an alpha-helix, that helix would be amphipathic, having one hydrophilic face bearing the acidic residues, and one hydrophobic face. When expressed in yeast, the artificial protein bearing this peptide efficiently activates the GAL1 gene which is ordinarily activated by GAL4. An otherwise identical protein with the novel 15 amino acids in a scrambled order, and which is thus unable to form an amphipathic structure, does not activate GAL1 transcription.


Three-independent-compartment chamber to study in vitro commissural synapses.
We describe a novel chamber in which the two intact neonatal rat hippocampi and the commissural fibers are placed in three independent compartments separated by latex membranes and perfused selectively with different solutions. A set of control tests showed that the compartments are well isolated: 1) methylene blue or eosin applied to one compartment did not diffuse to other compartments when verified via the microscope, and spectrophotometry revealed that <1/10.000th of the dye diffuses to other compartments; 2) tetrodotoxin (1 microM) applied to the commissural compartment blocked the synaptic responses evoked contralaterally without affecting those evoked on the ipsilateral side. This chamber enables a wide range of experiments that cannot be performed in conventional chambers, e.g., to study the maturation and plasticity of the commissural connections, bilateral synchronization of the rhythmic activities in the limbic system, commissural propagation of the epileptiform activities, etc.


Should cryopreserved epididymal or testicular sperm be recovered from obstructive azoospermic men for ICSI?
To determine the effect of the anatomical site of sperm recovery on intracytoplasmic sperm injection (ICSI) embryo implantation, pregnancy and live birth rates in couples with isolated obstructive azoospermia as the sole cause of infertility. Controlled, single centre, retrospective clinical study. University Hospital, Centre for Reproductive Medicine. One hundred and fifty-one cycles of ICSI were performed, using surgically recovered sperm, between August 1996 and March 2002. The outcome of ICSI, with surgically recovered sperm, was compared between epididymal (Group E) and testicular (Group T) derived sperm. Inclusion was limited to couples undergoing their first treatment cycle, where female age was < or =39 years and a minimum of five oocytes were available for injection. Women with a history of ovarian surgery, ultrasonic evidence of polycystic ovaries, uterine anomalies or hydrosalpinx were excluded. Clinical pregnancy, implantation and live birth rate. Forty-two of 151 cycles met the strict inclusion criteria. Groups E and T were comparable with respect to age, basal serum FSH, ovarian response; number of oocytes injected and number of embryos available and transferred. No difference existed between Groups E and T in implantation, clinical pregnancy or live birth rate (28.8% vs 25.8%, 42.9% vs 42.9% and 39.3% vs 42.9%, respectively). Cryopreserved epididymal and testicular sperm, from men with obstructive azoospermia, appear equally effective in ICSI. Epididymal recovery should remain the method of first choice for obstructive azoospermic men but further study of sperm DNA damage rates in different testicular sites is required.


Pollinator directionality as a response to nectar gradient: promoting outcrossing while avoiding geitonogamy.
Plants with multiple flowers could be prone to autonomous self-pollination and insect-mediated geitonogamy, but physiological and ecological features have evolved preventing costs related to autogamy. We studied the rare perennial herb Dictamnus albus as a model plant, with the aim of describing the plant-pollinator system from both plant and pollinator perspectives and analysing features that promote outcrossing in an entomophilous species. The breeding system and reproductive success of D. albus were investigated in experimental and natural conditions, showing that it is potentially self-compatible, but only intra-inflorescence insect-mediated selfing is possible. Nectar analysis showed gender-biased production towards the female phase, which follows the male phase, and during flowering, full blooming is found in flowers at the bottom of the raceme. Among a wide spectrum of insect visitors, three genera (Bombus, Apis, Megachile) were found to be principal pollinators. A study of insect behaviour showed a tendency towards bottom-to-top flights for the most important pollinators Bombus spp. and Apis mellifera: upward movements on the racemes could be explained by foraging behaviour, from more to less rewarding flowers. In accordance with the 'declining reward hypothesis', bumblebees and honeybees leave the plant when gain of reward is low, after which few flowers are visited, reducing the chance of self-pollen transfer among flowers. Intra-flower self-pollination is prevented in D. albus by protandry and herkogamy, while the nectar-induced sequential pattern of pollinator visits avoids geitonogamy and tends to maximise pollen export, promoting outcrossing. All these features for preventing selfing benefit plant fitness and population genetic structure.


Does the number of diapausing eggs laid on bark affect the population dynamics of the spider mite Panonychus mori?
We studied the relationship between number of diapausing eggs produced by the spider mite Panonychus mori and the subsequent population trend for a period of 3 years. Panonychus mori showed a single population density peak on its host plant moonseed, Cocculus trilobus. The position and height of this peak were correlated with the density of diapausing eggs around the moonseed leaf buds produced the winter before. In 1994 the density of diapausing eggs measured in February was 4.3/bud, which was 6-14 times higher than the density of diapausing eggs for the same period in 1995 (0.3/bud) and 1996 (0.7/bud). The subsequent population density peak in 1994 occurred in mid June and was about 2.5 times higher than the peaks in 1995 and 1996, which both occurred early September. Thus, the present study showed a positive correlation between the density of diapausing eggs on the host plant and the start and the extend of the population increase the next growing season. Predators associated with the spider mite population were phytoseiid mites, especially Amblyseius eharai was well synchronized with the spider mite density in 1994. Field observations revealed that P. mori produced diapausing eggs in response to short photoperiod in early October each year, which corresponded with the timing predicted by the critical photoperiod around 13 h at 18 degrees C, as assessed in laboratory trials. Diapause ended by early April when egg hatchability attained about 50% and eggs took 9 days to hatch at 25 degrees C and a 16L:8D photoperiod. Hatching in early April was twice faster than in late February.


Identification of Legionella from clinically diagnosed pneumonia patients and environmental samples.
Legionnaires' disease is a multisystem disease with life-threatening acute and severe form of pneumonia which is responsible for 2-9% pneumonia with high mortality. Eighty six respiratory tract samples and urine were collected from clinically diagnosed pneumonia patients and 12 water samples were collected from different environment. Identification of Legionella was done by culture and Polymerase Chain Reaction (PCR) of respiratory tract samples and environmental samples and Legionella Antigen (Ag) in urine was detected by Immunochromatographic test (ICT). Legionella was identified from 4 (4.65%) clinically diagnosed pneumonia patients of which 1(1.16%) case was culture positive, 1(1.16%) case was urine ICT positive and PCR was positive in all four cases. Of the 12 water samples tested, 4 (33.33%) samples were Legionella positive by PCR but culture results of these samples were negative. Identification of Legionella should be done by PCR in parallel with culture and urine ICT. Detection of Legionella in environmental samples is also needed to explore possible links between the water sources and disease transmission in population.


Dietary fats, fatty acids and insulin resistance: short review of a multifaceted connection.
Insulin resistance is a growing worldwide phenomenon, which progressively develops over years, and finally, if unchecked, predisposes to cardiovascular disease and diabetes mellitus type 2. Insulin resistance is a generalized metabolic disorder characterized by inefficient insulin function in skeletal muscle, liver and adipocytes. There is growing evidence that an increased free fatty acid level, and more importantly, the relative amounts of saturated and unsaturated fatty acids contributing to it, plays an important role in the development of insulin resistance. In turn, this is a reflection of the composition of dietary fat. Ultimately both the dietary intake and plasma levels determine the fatty acid composition of cell membranes. Higher levels of membrane saturated fatty acids seem to greatly impair the action of insulin, whereas the presence of polyunsaturated fatty acids, especially of the omega-3 and -6 families, in contrast, improves insulin sensitivity. In vitro studies, however, have not always corroborated the clinical evidence. Possible roles played by the various saturated and unsaturated fatty acids in the insulin-signaling pathway are discussed in light of recent evidence. Fatty acids have also been shown to alter gene expression in cells, in particular the peroxisome proliferator-activated receptor-gamma2 gene, adding to this multifaceted connection. As man has moved over the centuries from a hunter-gatherer diet to greater intakes of saturated and trans-fatty acids, insulin resistance has appeared with its related pathology. Greater understanding of the role played by dietary fat and plasma fatty acids in pathogenesis of insulin resistance, will allow for more timely prevention and improved treatment in the future.


Effect of short-term meditation training in central serous chorioretinopathy.
Stress and Type A personality are established risk factors for the development of central serous chorioretinopathy (CSC). Meditation is known to have a positive effect on reducing stress levels. This study aimed to assess the effect of short-term meditation training in patients of CSC. A pilot study was conducted where 40 patients diagnosed with acute and non-resolving CSC were randomly assigned to either of two groups - meditation training and routine care (without meditation). The primary outcome measure was time to resolution of CSC based on optical coherence tomography and fluorescein angiography. Secondary outcome measures were changes in anxiety score (State-Trait Anxiety Inventory [STAI] scores) and blood pressure. The patients were followed up for a minimum period of 4 months. Twenty cases were included in each group. The demographic pattern, baseline swept-source optical coherence tomography parameters, and STAI scores were similar in both groups. The time to disease resolution was 9.4 ± 4.22 weeks in the meditation group and 19.5 ± 2.79 weeks in the nonmeditation group (P < 0.001). At 4 months, CSC had failed to resolve in 60% of patients with routine care compared with 8% in cases following short-term meditation training. STAI scores showed a reduction in stress levels in the meditation group. Furthermore, statistically significant improvement in systolic and diastolic blood pressures was also observed following meditation training. Short-term meditation training may be a useful approach in the management of patients with CSC as it tends to reduce stress and prehypertension, and promotes earlier resolution of the condition. However, patient's motivation to complete and pursue the meditation training is a significant barrier.


Right pneumothorax resulting from an endocardial screw-in atrial lead in an implantable cardioverter defibrillator system.
This report describes a rare case of a patient undergoing implantation of a cardioverter defibrillator in whom a right pneumothorax resulting from an endocardial screw-in atrial lead was observed. Pericardial effusion, substantial changes in lead impedance, andpacing and sensing thresholds were not observed. Pneumothorax disappeared spontaneously and has not reoccurred during follow-up with conservative therapy alone.


Postural control strategy after incomplete spinal cord injury: effect of sensory inputs on trunk-leg movement coordination.
Postural control is affected after incomplete spinal cord injury (iSCI) due to sensory and motor impairments. Any alteration in the availability of sensory information can challenge postural stability in this population and may lead to a variety of adaptive movement coordination patterns. Hence, identifying the underlying impairments and changes to movement coordination patterns is necessary for effective rehabilitation post-iSCI. This study aims to compare the postural control strategy between iSCI and able-bodied populations by quantifying the trunk-leg movement coordination under conditions that affects sensory information. 13 individuals with iSCI and 14 aged-matched able-bodied individuals performed quiet standing on hard and foam surfaces with eyes open and closed. We used mean Magnitude-Squared Coherence between trunk-leg accelerations measured by accelerometers placed over the sacrum and tibia. We observed a similar ankle strategy at lower frequencies (f ≤ 1.0 Hz) between populations. However, we observed a decreased ability post-iSCI in adapting inter-segment coordination changing from ankle strategy to ankle-hip strategy at higher frequencies (f > 1.0 Hz). Moreover, utilizing the ankle-hip strategy at higher frequencies was challenged when somatosensory input was distorted, whereas depriving visual information did not affect balance strategy. Trunk-leg movement coordination assessment showed sensitivity, discriminatory ability, and excellent test-retest reliability to identify changes in balance control strategy post-iSCI and due to altered sensory inputs. Trunk-leg movement coordination assessment using wearable sensors can be used for objective outcome evaluation of rehabilitative interventions on postural control post-iSCI.


Dissecting the role of conformational change and membrane binding by the bacterial cell division regulator MinE in the stimulation of MinD ATPase activity.
The bacterial cell division regulators MinD and MinE together with the division inhibitor MinC localize to the membrane in concentrated zones undergoing coordinated pole-to-pole oscillation to help ensure that the cytokinetic division septum forms only at the mid-cell position. This dynamic localization is driven by MinD-catalyzed ATP hydrolysis, stimulated by interactions with MinE's anti-MinCD domain. This domain is buried in the 6-β-stranded MinE "closed" structure, but is liberated for interactions with MinD, giving rise to a 4-β-stranded "open" structure through an unknown mechanism. Here we show that MinE-membrane interactions induce a structural change into a state resembling the open conformation. However, MinE mutants lacking the MinE membrane-targeting sequence stimulated higher ATP hydrolysis rates than the full-length protein, indicating that binding to MinD is sufficient to trigger this conformational transition in MinE. In contrast, conformational change between the open and closed states did not affect stimulation of ATP hydrolysis rates in the absence of membrane binding, although the MinD-binding residue Ile-25 is critical for this conformational transition. We therefore propose an updated model where MinE is brought to the membrane through interactions with MinD. After stimulation of ATP hydrolysis, MinE remains bound to the membrane in a state that does not catalyze additional rounds of ATP hydrolysis. Although the molecular basis for this inhibited state is unknown, previous observations of higher-order MinE self-association may explain this inhibition. Overall, our findings have general implications for Min protein oscillation cycles, including those that regulate cell division in bacterial pathogens.


Sequence and functional analysis of a 7.2 kb DNA fragment containing four open reading frames located between RPB5 and CDC28 on the right arm of chromosome II.
In a coordinated approach, several laboratories sequenced Saccharomyces cerevisiae chromosome II during the European BRIDGE project. Here we report on the sequence and functional analysis of a 7217 bp fragment located on the right arm of chromosome II between RPB5 and CDC28. The fragment contains four open reading frames probably encoding proteins of 79.2 kDa (corresponding gene YBR156c), 12.1 kDa (YBR157c), 62.7 kDa (YBR158w) and 38.7 kDa (YBR159w). All four open reading frames encode new proteins, as concluded from data base searches. The respective genes were destroyed by gene replacement in one allele of diploid cells. After sporulation and tetrad analysis, the resulting mutant haploid strains were investigated. No phenotype with respect to spore germination, viability, carbohydrate utilization, and growth was found for YBR157c, encoding the smallest open reading frame investigated. Gene replacement within the YBR156c gene encoding a highly basic and possibly nuclear located protein was lethal. Ybr158 revealed similarities to the Grrl (Cat80) protein with respect to the leucine-rich region. Cells harboring a mutation in the YBR158w gene showed strongly reduced growth as compared to the wild-type cells. The protein predicted from YBR159w shared 33% identical amino acid residues with the human estradiol 17-beta-hydroxysterol dehydrogenase 3. Haploid ybr159c mutants were only able to grow at reduced temperatures, but even under these conditions the mutants grew slower than wild-type strains.


Mesenchymal stromal cells primed with paclitaxel provide a new approach for cancer therapy.
Mesenchymal stromal cells may represent an ideal candidate to deliver anti-cancer drugs. In a previous study, we demonstrated that exposure of mouse bone marrow derived stromal cells to Doxorubicin led them to acquire anti-proliferative potential towards co-cultured haematopoietic stem cells (HSCs). We thus hypothesized whether freshly isolated human bone marrow Mesenchymal stem cells (hMSCs) and mature murine stromal cells (SR4987 line) primed in vitro with anti-cancer drugs and then localized near cancer cells, could inhibit proliferation. Paclitaxel (PTX) was used to prime culture of hMSCs and SR4987. Incorporation of PTX into hMSCs was studied by using FICT-labelled-PTX and analyzed by FACS and confocal microscopy. Release of PTX in culture medium by PTX primed hMSCs (hMSCsPTX) was investigated by HPLC. Culture of Endothelial cells (ECs) and aorta ring assay were used to test the anti-angiogenic activity of hMSCsPTX and PTX primed SR4987(SR4987PTX), while anti-tumor activity was tested in vitro on the proliferation of different tumor cell lines and in vivo by co-transplanting hMSCsPTX and SR4987PTX with cancer cells in mice. Nevertheless, despite a loss of cells due to chemo-induced apoptosis, both hMSCs and SR4987 were able to rapidly incorporate PTX and could slowly release PTX in the culture medium in a time dependent manner. PTX primed cells acquired a potent anti-tumor and anti-angiogenic activity in vitro that was dose dependent, and demonstrable by using their conditioned medium or by co-culture assay. Finally, hMSCsPTX and SR4987PTX co-injected with human cancer cells (DU145 and U87MG) and mouse melanoma cells (B16) in immunodeficient and in syngenic mice significantly delayed tumor takes and reduced tumor growth. These data demonstrate, for the first time, that without any genetic manipulation, mesenchymal stromal cells can uptake and subsequently slowly release PTX. This may lead to potential new tools to increase efficacy of cancer therapy.


Evidence for targeting thioredoxin reductases with ferrocenyl quinone methides. A possible molecular basis for the antiproliferative effect of hydroxyferrocifens on cancer cells.
Many anticancer compounds are strong inhibitors of thioredoxin reductases (TrxRs), selenoenzymes involved in cellular redox regulation. This study examined the effect of two hydroxyferrocifens (1, FcOH; 2, FcOHTAM) and of their corresponding quinone methides (QMs), 1-QM, and 2-QM, on these enzymes. In vitro, both QMs were more potent TrxR inhibitors (IC50 ≈ 2.5 μM) than the hydroxyferrocifens (IC50 ≈ 15 μM). This inhibition was due to a Michael addition of the penultimate selenocysteine residue of TrxRs to the QMs. In Jurkat cancer cells, both 2 and 2-QM inhibited TrxRs in the same proportion, leading to accumulation of oxidized forms of thioredoxin, while 1 and 1-QM were scarcely effective. This difference of behavior was ascribed to the competitive conversion of 1-QM to an inactive indene in protic medium. This set of experiments confirms for the first time the role played by ferrocenyl quinone methides on several biological targets and gives a molecular basis for these effects. It also highlights differences in the mechanisms of action of 1 and 2 in cancer cells.


Fluorescence in situ hybridization with rDNA probes on chromosomes of two nucleolus organizer region phenotypes of a species of Eigenmannia (Pisces, Gymnotoidei, Sternopygidae).
Nucleolus organizer regions (NORs) were analysed in two related and geographically close populations of Eigenmannia sp.1 (Pisces, Gymnotoidei, Sternopygidae) using silver staining and fluorescence in situ hybridization (FISH). The two populations differed in their Ag-NOR phenotypes, displaying fixed differences in the NOR-bearing chromosome pairs. FISH with rDNA probes showed that these differences were due to the location of rDNA cistrons. This finding, showing fixed NOR differences between two populations belonging to the same species in a connected river system, is highly significant in terms of evolutionary change, possibly indicating an initial step of genetic differentiation. This result also has important implications from the cytosystematic point of view, as NORs usually have a very constant karyotypic location in fish species and have been used as species-specific chromosome markers.


Parietal bone thickness for predicting operative transfusion and blood loss in patients undergoing spring-mediated cranioplasty for nonsyndromic sagittal craniosynostosis.
Variables that can predict outcomes in patients with craniosynostosis, including bone thickness, are important for surgical decision-making, yet are incompletely understood. Recent studies have demonstrated relative risks and benefits of surgical techniques for correcting head shape in patients with nonsyndromic sagittal craniosynostosis. The purpose of this study was to characterize the relationships between parietal bone thickness and perioperative outcomes in patients who underwent spring-mediated cranioplasty (SMC) for nonsyndromic sagittal craniosynostosis. Patients who underwent craniectomy and SMC for nonsyndromic sagittal craniosynostosis at a quaternary pediatric hospital between 2011 and 2021 were included. Parietal bone thickness was determined on patient preoperative CT at 27 suture-related points: at the suture line and at 0.5 cm, 1.0 cm, 1.5 cm, and 2.0 cm from the suture at the anterior parietal, midparietal, and posterior parietal bones. Preoperative skull thickness was compared with intraoperative blood loss, need for intraoperative transfusion, and hospital length of stay (LOS). Overall, 124 patients with a mean age at surgery ± SD of 3.59 ± 0.87 months and mean parietal bone thickness of 1.83 ± 0.38 mm were included in this study. Estimated blood loss (EBL) and EBL per kilogram were associated with parietal bone thickness 0.5 cm (ρ = 0.376, p < 0.001 and ρ = 0.331, p = 0.004; respectively) and 1.0 cm (ρ = 0.324, p = 0.007 and ρ = 0.245, p = 0.033; respectively) from the suture line. Patients with a thicker parietal bone 0.5 cm (OR 18.08, p = 0.007), 1.0 cm (OR 7.16, p = 0.031), and 1.5 cm (OR 7.24, p = 0.046) from the suture line were significantly more likely to have undergone transfusion when controlling for age, sex, and race. Additionally, parietal bone thickness was associated with hospital LOS (β 0.575, p = 0.019) when controlling for age, sex, and race. Patient age at the time of surgery was not independently associated with these perioperative outcomes. Parietal bone thickness, but not age at the time of surgery, may predict perioperative outcomes including transfusion, EBL, and LOS. The need for transfusion and EBL were most significant for parietal bone thickness 0.5 cm to 1.5 cm from the suture line, within the anticipated area of suturectomy. For patients undergoing craniofacial surgery, parietal bone thickness may have important implications for anticipating the need for intraoperative transfusion and hospital LOS.


Peritoneal catheter tip location during non-complicated continuous ambulatory peritoneal dialysis.
In the present study, we evaluated the relationship between 1. the volume and rate of dialysis outflow and subsequent inflow, 2. the patient's impression of the location of the catheter tip and 3. the stability of the catheter tip location. Thirteen patients were studied on 2 random occasions (periods 1 and 2). Inflow (L/min) was significantly faster than outflow (p less than 0.05). No catheter tips were located in the far upper part of the abdomen. Outflow with the catheter tip located in the middle part of the abdomen was significantly lower than with the tip located in the inferior quadrants (p less than 0.02). Two patients were able to feel the catheter tip at Period 1, and 4 at Period 2, but only 1 patient was able to state the exact location identical to fluoroscopy. Ninety-two percent of the fluoroscopic evaluations showed catheter tips located in the same anatomical regions in upright as well as supine positions. If vertical "neighbour" anatomical regions were included in the evaluation of the catheter tip migrations, all catheter tips were located at the same or the vertical "neighbour" region in the 2 study periods.