[Impact of lipopolysaccharide-induced inflammation on sperm quality in male rats and its possible mechanisms].
To investigate the influence of lipopolysaccharide (LPS)-induced inflammation on sperm quality in male rats and its possible mechanisms. Thirty-six male SD rats were randomly divided into groups A (control), B (12 h LPS), C (24 h LPS) and D (72 h LPS), the former group injected intraperitoneally with sterile saline, and the latter three with LPS at 5 mg/kg and sacrificed at 12, 24 and 72 hours respectively after treatment. Then the left epididymides of the rats were harvested for detection of the sperm count and motility in the cauda epididymis, measurement of the relative sperm count value, examined the content of malondialdehyde (MDA) and activity of superoxide dismutase (SOD) in the epididymal plasma, and determined the apoptosis rate of spermatogenic cells by flow cytometry (FCM). Compared with the parameters in group A, sperm motility in the cauda epididymis was decreased in groups B ([68.01 ± 1.80]% vs [62.28 ± 4.06]%, P < 0.05), C ([68.01 ± 1.80]% vs [45.35 ± 3.39]%, P < 0.05) and D ([68.01 ± 1.80]% vs [34.85 ± 4.42]%, P < 0.01), and so was the sperm count in the cauda epididymis ([38.94 ± 4.08] vs [37.15 ± 2.54] ×106/ 100 mg, P > 0.05; [38.94 ± 4.08] vs [31.97 ± 2.81] ×106/ 100 mg, P < 0.05; [38.94 ± 4.08] vs [28.60 ± 4.03] ×106/ 100 mg, P < 0.01), while the content of MDA in the epididymal plasma significantly increased ([4.66 ± 1.49] vs [15.95 ± 3.26] nmol/mg prot, P < 0.01; [4.66 ± 1.49] vs [12.93 ± 2.54] nmol/mg prot, P < 0.01; [4.66 ± 1.49] vs [9.67 ± 1.68] nmol/mg prot, P < 0.05), the activity of SOD reduced ([879.335 ± 105.089] vs [729.265 ± 93.783] U/mg prot, P > 0.05; [879.335 ± 105.089] vs [694.126 ± 58.530] U/mg prot, P < 0.05; [879.335 ± 105.089] vs [655.352 ± 115.215] U/mg prot, P < 0.05), and the apoptosis rate of spermatogenic cells dramatically elevated ([4.21 ± 1.67]% vs [11.01 ± 3.30]%, P < 0.05; [4.21 ± 1.67]% vs [23.88 ± 4.58]%, P < 0.01; [4.21 ± 1.67]% vs [41.28 ± 2.28]%, P < 0.01). LPS-induced inflammation damages spermatogenic cells and the quality of epididymal sperm in male rats in a time-dependent manner, which is associated with oxidative stress injury and cell apoptosis in the reproductive system.


New physician recognition program for cardiovascular care announced.
Physicians and medical groups that provide quality care to patients with heart disease or stroke now can be recognized under a program launched last month by the National Committee for Quality Assurance and the American Heart Association/American Stroke Association.


Infusing the capital review process with rigor and discipline.
Intermountain Healthcare gleaned four key insights from inside and outside the industry when reviewing best practices in capital decision making: Evidence-based decision making and disciplined analysis are as critical in healthcare finance as in any other industry. Comparing various scenarios under value-based payment allows for better modeling than does performing traditional, volume-based pro formas. Reviewing large capital projects at a granular level helps identify opportunities to add or subtract services. A comprehensive look-back process identifies lessons learned from approved projects-and helps ensure that proposals are defensible.


Lethal events during gas sparging in animal cell culture.
The lethal effects of gas sparging on hybridoma cells obtained from a chemostat culture were examined in a bubble column. Experiments were performed to identify and quantify the main hazardous event: bubble formation, bubble rising, or bubble breakup. The results indicate that bubble breakup is the main cause of cell death. The protective activity of the surfactant Pluronic F68 against sparging seems to result from a direct interaction with the cells rather than influencing bubble-liquid interface properties.


[A treatment with rosuvastatin induced a reduction of arterial pressure and a decrease of oxidative stress in spontaneously hypertensive rats].
The aim of this study was to appreciate consequences of rosuvastatin administration on hemodynamic function, vascular oxidative stress and ischemia/reperfusion disorders in normotensive and hypertensive rats. At 10 weeks of age, spontaneously hypertensive rats (SHR, n=20) and normotensive Wistar Kyoto male rats (WKY, n=20) were divided into four groups and given, either vehicle or 10 mg/kg/day of rosuvastatin by gavage for 3 weeks. Systolic blood pressure was assessed every week. At the end of these treatments, vascular NADPH oxidase activity was evaluated by chemiluminescence (lucigenin 0.5 microM). Hearts were isolated and perfused according to the Langendorff method and were subjected to 30 min of global ischemia. Reactive oxygen species (ROS) produced during reperfusion were quantified by electron spin resonance (ESR) spectroscopy using a spin probe (CP-H, 1 mM). After one week of treatment, rosuvastatin reduced the arterial pressure in SHR rats (180.3 +/- 2.1, SHR vs 169.7 +/- 2.3 mmHg, SHR+rosuvastatin; p < 0.01), without lowering plasma cholesterol levels; these effects were not observed in WKY. NADPH activity was 25% higher in control SHR rat aortas compared to control WKY, and was reduced by rosuvastatin in SHR rats. In isolated rat hearts subjected to ischemia/reperfusion sequences, there was a deterioration in functional parameters in control SHR compared to control WKY hearts. Rosuvastatin decreased post-ischemic contracture in WKY hearts by 50% (41.5 +/- 7.5, WKY control vs 18.4 +/- 4.6 mmHg, WKY+rosuvastatin; p < 0.01) and increased left ventricular developed pressure. This beneficial effect was accompanied by a decrease in ROS detected by ESR during reperfusion (312.5 +/- 45.3, WKY control; vs 219.3 +/- 22.9 AUC/mL, WKY+rosuvastatin; p < 0.05). In conclusion, these results are in accordance with the hypothesis that oxidative stress plays a crucial role in the pathogenesis of cardiovascular diseases including hypertension, and demonstrate the beneficial effects of rosuvastatin.


Attitudes to visits by children to parents hospitalised with acute psychiatric illness.
There is no published research on attitudes of psychiatrists towards children visiting parents who are acutely-unwell and inpatients in psychiatric hospitals. Nor is there information on facilities available for such visits. (I) To assess the attitudes of Irish psychiatrists towards children visiting. (II) To determine the availability of child-friendly facilities within admission units. A questionnaire was posted to every consultant psychiatrist accepting acute adult admissions in the Republic of Ireland and Northern Ireland. The response rate was 69%. Ninty-seven per cent were in favour of children visiting. Almost half felt that decisions on visits should depend on the particular situation, considering the child, parent, ward, etc. However, only 11% of units had a room/area designated for children visiting. 90% had no facilities they considered child-friendly on their unit. A majority felt that arrangements for children visiting were inadequate. This topic is of interest to psychiatrists, and can be contentious, particularly when considering supervision of, and legal responsibility for, children visiting. Guidance on these issues would aid psychiatrists and hospital management. Poor facilities and infrequent visits may be a factor in the early development of stigma towards mental illness. Further research, improvements in facilities and staff training in liaison with children are needed.


Influence of halogen bonding interaction on supramolecular assembly of coordination compounds; head-to-tail N···X synthon repetitivity.
In this study, N-(3-halophenyl)-2-pyrazinecarboxamide ligands, L(3-F), L(3-Cl), L(3-Br), and L(3-I), carrying a different halogen atom on the phenyl meta-position and N-phenyl-2-pyrazinecarboxamide ligand, L(H), have been employed for the synthesis of 12 mercury(II) complexes, [HgCl2(L(H))]n, 1, [HgCl2(L(3-Cl))]n, 2, [Hg2Cl4(L(3-Br))2], 3, [Hg2Cl4(L(3-I))2], 4, [Hg2Br4(L(H))2], 5, [HgBr2(L(3-F))], 6, [HgBr2(L(3-Cl))], 7, [HgBr2(L(3-Br))], 8, [HgBr2(L(3-I))], 9, [Hg2I4(L(H))2], 10, [HgI2(L(3-Br))], 11, and [HgI2(L(3-I))]n, 12. Interestingly, structural analysis clearly shows that, by the replacing of coordinated anions from chloride with bromide and iodide in each series containing the same ligand, the coordination geometry and structural motif of the resulting compounds have been dramatically affected. One of the common features in the crystal structures of these complexes is that there is a strong tendency to form halogen bonding synthons between adjacent halophenyl and pyrazine rings. The influence of these halogen bonding interactions on the supramolecular assemblies has been discussed with the help of geometrical analysis and theoretical calculations. The X···N halogen bonding distances are 2.5-9.4% shorter than the sum of the van der Waals radii of nitrogen and halogen atoms. Theoretical methods also show the halogen bonding energies within a range of -27.86 to -46.15 kJ·mol(-1). In all complexes synthesized here, the pyrazine ring is coordinated to the mercury(II) ion through the N atom syn to the carbonyl. Therefore, the second common feature of the crystal structures for complexes studied here is the selectivity of the metal ion coordination site. The halogen bond synthon repetitivity across these compounds and selectivity in the mercury(II) ion coordination site further point to application in the coordination crystal engineering research field.


Clinical and economic burden of dyspnea and other COPD symptoms in a managed care setting.
The degree to which symptoms such as dyspnea affect patients with COPD is individualized. To address the gap between clinical symptom measures and self-perceived disease burden, we investigated the symptom status of adult patients with COPD and followed with an administrative claims analysis of health care resource utilization and costs. This was a hybrid US observational study consisting of a cross-sectional patient survey followed by a retrospective analysis of administrative claims data. The primary COPD symptom measures were the modified Medical Research Council (mMRC) Dyspnea scale and the COPD Assessment Test (CAT). A total of 673 patients completed the survey. Of these, 65% reported mMRC grades 0-1 (low symptomatology) and 35% reported mMRC grades 2-4 (high symptomatology); 25% reported CAT score <10 (low symptomatology) and 75% reported CAT score ≥10 (high symptomatology). More patients with high symptomatology (by either measure) had at least one COPD-related inpatient hospitalization, emergency room visit, physician office visit, or other outpatient services, and filled at least one COPD-related prescription medication vs patients with low symptomatology. COPD-related costs were higher for patients with high symptomatology than patients with low symptomatology. In a multivariate analysis, COPD-related costs were also higher in patients reporting severe symptoms. Patients with high COPD symptomatology utilized more health care resources and had higher COPD-related health care costs during the 6-month post-survey period than patients with low symptomatology.


Effects of nisin and temperature on survival, growth, and enterotoxin production characteristics of psychrotrophic Bacillus cereus in beef gravy.
The presence of psychrotrophic enterotoxigenic Bacillus cereus in ready-to-serve meats and meat products that have not been subjected to sterilization treatment is a public health concern. A study was undertaken to determine the survival, growth, and diarrheal enterotoxin production characteristics of four strains of psychrotrophic B. cereus in brain heart infusion (BHI) broth and beef gravy as affected by temperature and supplementation with nisin. A portion of unheated vegetative cells from 24-h BHI broth cultures was sensitive to nisin as evidenced by an inability to form colonies on BHI agar containing 10 micrograms of nisin/ml. Heat-stressed cells exhibited increased sensitivity to nisin. At concentrations as low as 1 microgram/ml, nisin was lethal to B. cereus, the effect being more pronounced in BHI broth than in beef gravy. The inhibitory effect of nisin (1 microgram/ml) was greater on vegetative cells than on spores inoculated into beef gravy and was more pronounced at 8 degrees C than at 15 degrees C. Nisin, at a concentration of 5 or 50 micrograms/ml, inhibited growth in gravy inoculated with vegetative cells and stored at 8 or 15 degrees C, respectively, for 14 days. Growth of vegetative cells and spores of B. cereus after an initial period of inhibition is attributed to loss of activity of nisin. One of two test strains produced diarrheal enterotoxin in gravy stored at 8 or 15 degrees C within 9 or 3 days, respectively. Enterotoxin production was inhibited in gravy supplemented with 1 microgram of nisin/ml and stored at 8 degrees C for 14 days; 5 micrograms of nisin/ml was required for inhibition at 15 degrees C. Enterotoxin was not detected in gravy in which less than 5.85 log10 CFU of B. cereus/ml had grown. Results indicate that as little as 1 microgram of nisin/ml may be effective in inhibiting or retarding growth of and diarrheal enterotoxin production by vegetative cells and spores of psychrotrophic B. cereus in beef gravy at 8 degrees C, a temperature exceeding that recommended for storage or for most unpasteurized, ready-to-serve meat products.


A clear and present danger: inflammasomes DAMPing down disorders of pregnancy.
When the normal progression of pregnancy is threatened, inflammatory processes are often amplified in order to minimize detrimental effects and eliminate noxious agents. Inflammasomes are unique, intracellular, multiprotein assemblies that enable caspase-1 mediated proteolytic processing of the proinflammatory cytokine interleukin-1β, levels of which are elevated in some forms of preterm birth and maternal metabolic disorders. A comprehensive review based on a search of PubMed and Medline for terms and combinations of terms incorporating 'inflammation', 'inflammasome', 'pregnancy', 'preterm birth', 'pre-eclampsia', 'interleukin-1', 'caspase-1' and others selected to capture key articles. In the decade since the discovery of the inflammasome, between January 2002 and June 2014 over 2200 articles have been published. Articles in the reproductive field are scarce but there is clear evidence for a role of the inflammasome axis in pregnancy, preterm birth and the maternal metabolic syndrome. Further investigations on the inflammasome in pregnancy are needed in order to elucidate the biology of this unique structure in reproduction. Coordination of maternal, fetal and placental aspects of inflammasome function will potentially yield new information on the detection and transduction of host and non-host signals in the inflammatory response.


Case Report: Transcatheter Arterial Embolization for the Initial Management of Intra-Abdominal Hemorrhage From a Hepatic Tumor in a Cat.
An 8-year-old Ragdoll cat was admitted to our hospital after its owner noticed sudden lethargy. Abdominal ultrasonography showed a large amount of blood in the abdominal cavity, and the cat was diagnosed as having hemorrhagic shock caused by the rupture of an intra-abdominal mass. Blood transfusion was performed on the 1st day of hospitalization. On the 2nd day, contrast-enhanced computed tomography (CT) was performed, and hemorrhage from a mass originating in the caudate lobe of the liver was noted. Transcatheter arterial embolization (TAE) was performed to stop the bleeding from the mass using Gelpart to embolize the feeding artery. The following day, fever and elevation of liver enzyme levels were observed, but these subsided within a few days. At discharge 5 days after TAE, no fluid was found in the peritoneal cavity, and no further intra-abdominal bleeding occurred. Sixty-six days after TAE, we were able to perform resection surgery with the cat in good condition. A partial response was observed on CT performed before surgery. Histopathology revealed cholangiocellular adenoma. The cat was doing well as of postoperative day 549. This case indicates that TAE may be effective for initial hemostasis and stabilization of conditions in animals with tumor-induced hemorrhage.


An epidemiological survey on personality disorder in Andalusia (the PISMA-ep PD study).
Despite a significant clinical and social burden, there is a relative scarcity of epidemiological studies on Personality Disorder (PD). To determine the current prevalence of PD and the psychosocial correlates associated with this in the Andalusian population. We carried out a cross-sectional population mental-health survey in Andalusia, southern Spain. Thus, 4,518 randomly selected participants were interviewed following sampling using different standard stratification levels. We used the Spanish version of the SAPAS to estimate PD prevalence. In addition, a full battery of other instruments was utilized to explore global functionality, childhood abuse, maltreatment, threatening life events, personality traits (neuroticism, impulsivity and paranoia), medical and psychiatric comorbidities, family history of psychological problems and other potential risk factors for PD. PD prevalence (10.8%; 95% CI [9.8, 11.7]) and ran two different multivariate models for PD. We obtained the highest PD prevalence in those affected by any mental disorder plus those reporting having suffered childhood abuse, particularly sexual abuse. Additional potential risk factors or correlates of PD identified were: younger age, lower levels of functioning, less social support, poorer general health, having suffered maltreatment, threatening life events, higher suicidal risk scores and higher levels of both neuroticism and impulsivity. This study reports PD prevalence and risk correlates in consonance with similar findings reported in other Western populations. However, longitudinal studies are needed to elicit a more thorough group of prospective determinants of PD.


The in vitro effect of amrinone on platelet aggregation in human whole blood.
Amrinone was found to inhibit platelet aggregation in human whole blood in a dose dependent manner, and at physiological levels of the drug. Statistically significant drug-related decreases in aggregation were observed with collagen, ADP and arachidonic acid. Inhibition of aggregation was most marked with arachidonic acid, where greater than 90% inhibition was achieved at a drug concentration of 25 mugml-1. The aggregation profiles presented indicate that amrinone inhibits aggregation primarily through inhibition of thromboxane A2 synthesis.


Rhizobium pusense sp. nov., isolated from the rhizosphere of chickpea (Cicer arietinum L.).
A novel bacterial strain, designated NRCPB10(T), was isolated from rhizosphere soil of chickpea (Cicer arietinum L.) in Pusa, New Delhi, India. The 16S rRNA gene sequence of strain NRCPB10(T) showed highest similarity (98.9 %) to that of Rhizobium radiobacter NCPPB 2437(T), followed by Rhizobium larrymoorei AF3-10(T) (97.7 %) and Rhizobium rubi IFO 13261(T) (97.4 %). Phylogenetic analysis of strain NRCPB10(T) based on the housekeeping genes recA and atpD confirmed its position as distinct from recognized Rhizobium species. Levels of DNA-DNA relatedness between strain NRCPB10(T) and R. radiobacter ICMP 5785(T), R. larrymoorei LMG 21410(T) and R. rubi ICMP 6428(T) were 51.0, 32.6 and 27.3 %, respectively. Cellular fatty acids of strain NRCPB10(T) were C(18 : 1)ω7c (58.9 %), C(16 : 0) (15.5 %), C(19 : 0) cyclo ω8c (11.5 %), iso-C(16 : 1) (5.8 %), C(16 : 0) 3-OH (4.5 %), C(16 : 1)ω7c (2.1 %) and C(18 : 0) (1.3 %). The G+C content of the genomic DNA of strain NRCPB10(T) was 59.0 mol%. Strain NRCPB10(T) did not nodulate chickpea plants or induce tumours in tobacco plants. Phenotypic and physiological properties along with SDS-PAGE of whole-cell soluble proteins differentiated strain NRCPB10(T) from its closest phylogenetic neighbours. On the basis of data from the present polyphasic taxonomic study, strain NRCPB10(T) is considered to represent a novel species of the genus Rhizobium, for which the name Rhizobium pusense sp. nov. is proposed. The type strain is NRCPB10(T) ( = LMG 25623(T) = JCM 16209(T) = NCIMB 14639(T)).


Protein ubiquitination in lymphoid malignancies.
Human lymphoid malignancies inherit gene expression networks from their normal B-cell counterpart and co-opt them for their own oncogenic purpose, which is usually governed by transcription factors and signaling pathways. These transcription factors and signaling pathways are precisely regulated at multiple steps, including ubiquitin modification. Protein ubiqutination plays a role in almost all cellular events and in many human diseases. In the past few years, multiple studies have expanded the role of ubiquitination in the genesis of diverse lymphoid malignancies. Here, we discuss our current understanding of both proteolytic and non-proteolytic functions of the protein ubiquitination system and describe how it is involved in the pathogenesis of human lymphoid cancers. Lymphoid-restricted ubiquitination mechanisms, including ubiquitin E3 ligases and deubiquitinating enzymes, provide great opportunities for the development of targeted therapies for lymphoid cancers.


Hyaluronan production in vitro by fetal lung fibroblasts and epithelial cells exposed to surfactants of N-acetylcysteine.
Fetal human lung fibroblasts and feline lung epithelial cells were exposed to either a surfactant or N-acetylcysteine in various concentrations for 24-48 hours, after which the hyaluronan concentration in the culture medium was determined. Most of the experiments showed no stimulatory effect of either artificial or natural surfactant on hyaluronan synthesis. N-acetylcysteine 5-100 mg/mL induced progressive stimulation of hyaluronan synthesis by human fetal lung fibroblasts, resulting in a maximum hyaluronan concentration six times that released by unexposed cells. A slight increase in hyaluronan synthesis was also observed after exposure of feline fetal lung epithelial cells to N-acetylcysteine 50-100 micrograms/mL.


Ziziphus spina-christi (L.) fortified with Camellia sinensis mediates apoptosis, Notch-1 signaling, and mitigates obesity-induced non-alcoholic fatty liver.
The habit of drinking tea is highly prevalent and could be utilized to introduce more health benefits through fortification with medicinal plants. The purpose of this analysis was to assess the nutritional quality and health benefits of fortified Ziziphus tea (ZT) with green tea (GT) against obesity and non-alcoholic fatty liver disease (NAFLD). Proximate analysis and sensory evaluation were carried out on the fortified tea. In the in vivo study, 15 SD rats were used for each group. Flow cytometry was utilized for caspase 3 analysis. ELISA was used for the detection of tumor necrosis factor-alpha and adiponectin levels. Real-time PCR was used to detect Notch-1 and Hes-1 gene expression. The composition of fortified (GT+ZT) showed a significant improvement in the nutritional value represented by the increase in overall protein, crude fat, crude fiber, ash, carbohydrate, mineral contents, and antioxidant capacity. Treatment with GT+ZT restored the disturbance in body weight, lipid profile, liver function, glucose, insulin sensitivity index, and oxidative status. It reversed the changes in TNF-α and adiponectin levels. Their protective effects against NAFLD were indicated by the inhibition of hepatic caspase-3 activity, suppression of Notch-1, and Hes-1 gene expression and amelioration of high-fat diet (HFD)-induced histological alterations. Collectively, our findings, elucidate the precise mechanism of fortified ZT+GT for the attenuation of obesity-induced metabolic disorders and NAFLD via regulating lipolysis, TNF-α, adiponectin, apoptosis, and Notch-1 signaling pathways, and provide a foundation for an easily implemented healthy habit of drinking. PRACTICAL APPLICATIONS: The incorporation of bioactive compounds into functional foods is a growing market. Consumer attention in well-being has increased rapidly toward a fortified diet that provides additional health effects. The fortified (GT+ZT) tea may potentially serve as an easily implemented healthy drinking habit to prevent and manage obesity and NAFLD and reduce the risk of other diseases. Fortification with ZT improved the health-promoting functionality of GT through the enhancement of total protein, carbohydrates, antioxidant, and mineral contents. This was reflected by their synergetic therapeutic activity in ameliorating the disturbance in obesity-related disorders and NAFLD via regulating lipolysis, inflammation, oxidative stress, apoptosis, and Notch-1 signaling pathways. Therefore, (GT+ZT) could be considered functional foods which attribute to functional improvement and reduction in disease risk.


Dynamics of an externally driven cavitation bubble in an elastic microconfinement.
The subject of the present study is the dynamics of a single cavitation bubble in a spherical liquid cell surrounded by an infinite elastic solid. It is shown that volume confinement strongly affects the manifestation of the classical cavitation Blake threshold. In particular, at liquid cell sizes smaller than some critical size, the cavitation is completely suppressed by volumetric confinement. The system of equations for the dynamics of a confined bubble, accounting for the mass of gas in the bubble, surface tension, liquid compressibility, solid elasticity, and damping due to viscosity in the liquid cell, is derived. The pressure in the solid far away from the bubble is used as an external driving force. Linear analysis of the bubble dynamics, including consideration of the natural frequency and amplitude-phase frequency response of the bubble-in-cell system, is conducted. In the nonlinear case, bifurcation diagrams are considered to determine the dynamic response of small and large bubbles in the states below and above the cavitation threshold, respectively.


Parent-youth discrepancies in ratings of youth victimization: associations with psychological adjustment.
This study extends research examining the implications of parent-youth informant discrepancies on youth victimization. Latent class analysis (LCA) identified dyads distinguished by patterns of parent and youth report of victimization. Analyses examined how latent classes were related to adjustment (i.e., anxiety/depression, aggression, and delinquency) concurrently and at follow-up assessment (~2.5 years) in a socioeconomically and ethnically diverse sample. Participants were 485 youths (58.1% male; M age = 12.83 years, SD = 1.60) and their primary caregivers from the Project on Human Development in Chicago Neighborhoods. This study compared three classes of youths: (a) Parent > Youth (24.0%), (b) Youth > Parent (21.5%), and (c) Relative Agreement (54.5%). Findings did not support the hypothesis that groups reflecting parental underreporting of youth victimization experiences would show poor adjustment relative to all other classes longitudinally. Surprisingly, youths who self-reported lower levels of victimization than parents reported were at risk for maladjustment over time. This type of discrepant dyad may deserve more careful attention than previously considered in the literature.


Truth and falsity in group.
The universal tension and juxtaposition between truth seeking and truth evasion are explored in a contemporary relational context, drawing on Bion 's later ideas on group. Bion's key idea of "psi," or psychic evasiveness, refocuses group theory, supplementing intra- and inter-psychic perspectives with sociopolitical analysis. To some extent the psychotherapy group exists as a political "Establishment" and thus corresponds to psi. Using three illustrative case examples, the nature and nurture of truth evasion is considered, along with the purposes it serves and the forms it may take. The therapist must maintain a disruptive-creative influence on group process, but like other group members, he or she instead may accept and promote falsity. Whereas the therapist ensures the integrity of the culture, the members, and not solely the therapist, break up old relational patterns and experiment with new ones. Dynamic, evolving groups aid the leader in life-affirming truth-seeking, eventually challenging establishment tendencies and exposing falsity.


Radiation therapy as primary and adjuvant treatment for local and regional melanoma.
The role of radiation therapy as primary and adjuvant therapy for localized or locally advanced melanoma is controversial. To develop evidence-based guidelines, PubMed was searched using the keywords melanoma AND (radiation OR radiotherapy). These references were reviewed and the relevant articles selected. The articles were then reviewed for further references. Because of the paucity of prospective or randomized trials, no attempt was made to classify the quality of the results. No phase III trials of nodal irradiation for prevention of regional recurrence are available. A phase III trial is being completed by the Tasman Radiation Oncology Group. A phase II trial has been completed by the group. Multiple retrospective series have been published. The available data appear to confirm that nodal radiation therapy is effective in preventing nodal recurrence. No dose response or fraction size response was found. According to generally accepted guidelines, radiation therapy should be offered for patients who have nodes greater than 3 cm, more than 3 involved nodes, or extracapsular extension. For radiation therapy for the treatment of metastatic disease, a phase III trial showed that 50 Gy in 2.5-Gy fractions was as effective as 32 Gy in 8-Gy fractions, with 25% complete remission and 35% partial remission. In contrast, the retrospective studies support that larger fraction sizes, at least 4 Gy, are more effective. Adjuvant nodal irradiation appears to be effective for the prevention of nodal recurrence. Radiation therapy can also be effective for treatment of local disease, if surgery is not an option.


Clinical implications of a three-pore model of peritoneal transport.
The peritoneal barrier exchange characteristics are in this article described in terms of a three-pore model of membrane permselectivity. The peritoneal membrane during continuous ambulatory peritoneal dialysis (CAPD) is thus simulated to have a large number of small pores of radius 40-55 A, a small number of large pores of radius 200-300 A, and an abundance of transcellular pores of radius 4-5 A. Due to the heteroporous nature of the peritoneal membrane, peritoneal small solute sieving coefficients are of the order of 0.5-0.6, and not near unity, as predicted for a homoporous membrane having 50 A (radius) equivalent pores, but lacking transcellular pores. As a consequence, the dialysate during CAPD is diluted during the first 50-100 minutes of the dwell. Furthermore, there is a marked coupling between the increased net transperitoneal volume flow, occurring early in the cycle, and the transfer of "small" macromolecules, such as beta 2-microglobulin and albumin, across the peritoneal membrane. This coupling is, however, small for "large" macromolecules, such as IgG and IgM, or for small solutes. Increasing the peritoneal surface area, in computer simulations of peritoneal transport according to the three-pore model, causes the simulated intraperitoneal (i.p.) volume vs. time (V(t)) curves to peak earlier than during control, while the maximum volume ultrafiltered is not markedly affected. However, selectively increasing the glucose PS (mass transfer area coefficient) causes a reduction both in the peak time and the peak "height" of the V(t) curves. The latter pattern is also seen when the dialysate volume is reduced. It is concluded that a three-pore model of membrane permselectivity selectivity can adequately describe the kinetics of peritoneal transport of small and large solutes and of fluid.


Relative configuration, absolute configuration and absolute structure of three isomeric 8-benzyl-2-[(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1]octan-3-ones.
The title compounds, C21H22BrNO2, are isomeric 8-benzyl-2-[(4-bromophenyl)(hydroxy)methyl]-8-azabicyclo[3.2.1]octan-3-ones. Compound (I), the (±)-exo,syn-(1RS,2SR,5SR,9SR) isomer, crystallizes in the hexagonal space group R-3, while compounds (II) [the (+)-exo,anti-(1R,2S,5S,9R) isomer] and (III) [the (±)-exo,anti-(1RS,2SR,5SR,9RS) isomer] crystallize in the orthorhombic space groups P212121 and Pna21, respectively. The absolute configuration was determined for enantiomerically pure (II). For the noncentrosymmetric crystal of (III), its absolute structure was established. In the crystal structures of (I) and (II), an intramolecular hydrogen bond is formed between the hydroxy group and the heterocyclic N atom. In the crystal structure of racemic (III), hydrogen-bonded chains of molecules are formed via intermolecular O-H...O interactions. Additionally, face-to-edge π-π interactions are present in the crystal structures of (I) and (II). In all three structures, the piperidinone rings adopt chair conformations and the N-benzyl substituents occupy the equatorial positions.


Production and characterization of RNA aptamers specific for amyloid fibril epitopes.
One of the most fascinating features of amyloid fibrils is their generic cross-beta architecture that can be formed from many different and completely unrelated proteins. Nonetheless, amyloid fibrils with diverse structural and phenotypic properties can form, both in vivo and in vitro, from the same protein sequence. Here, we have exploited the power of RNA selection techniques to isolate small, structured, single-stranded RNA molecules known as aptamers that were targeted specifically to amyloid-like fibrils formed in vitro from beta(2)-microglobulin (beta(2)m), the amyloid fibril protein associated with dialysis-related amyloidosis. The aptamers bind with high affinity (apparent K(D) approximately nm) to beta(2)m fibrils with diverse morphologies generated under different conditions in vitro, as well as to amyloid fibrils isolated from tissues of dialysis-related amyloidosis patients, demonstrating that they can detect conserved epitopes between different fibrillar species of beta(2)m. Interestingly, the aptamers also recognize some other, but not all, amyloid fibrils generated in vitro or isolated from ex vivo sources. Based on these observations, we have shown that although amyloid fibrils share many common structural properties, they also have features that are unique to individual fibril types.


Pathogenic fungi and parasitoids of aphids present in air captures of migratory alates in the low-latitude plateau of Yunnan, China.
To survey fungal pathogens and parasitoids of aphids in the low-latitude plateau of Yunnan, southwest China, 3,553 migratory alates of Brevicoryne brassicae, Lipaphis erysimi, and Myzus persicae were attracted to a yellow-plus-plant trap from air during a full-year period and individually reared on cabbage leaves for 7-14 d at 18-22 degrees C and L:D 12:12. Among the trapped alates, 19.2% were killed by 10 species of aphid-pathogenic fungi after survival of 2.3 d (range, 1-7 d). Another 2.8% were mummified by the wasps Aphidius gifuensis, Diaeretella rapae, Ephedrus plagiator, and Aphelinus mali after survival of 4.9 d (range, 1-11 d). Most of the mycosed alates (77.8%) died from Entomophthorales predominated by Pandora neoaphidis (42.7%) and Zoophthora radicans (14.5%), followed by P. nouryi, Neozygites fresenii, Conidiobiolus spp., Entomophthora planchoniana, and Z. aphidis in decreasing frequencies. A mitosporic fungus, Lecanicillium lecanii, was found frequently in L. erysimi alates trapped in rainy season. However, B. brassicae alates captured in dry season were infected or parasitized very occasionally. The predeath fecundity of the infected or parasitized alates warranted successful colonization on plants, although greatly reduced, and was well shown by the fitted probability for a given fecundity per capita and the increasing mean size of their progeny colonies. Contagious transmission of the alate-borne mycosis in most of the colonies caused high progeny mortalities within 14 d. The results highlight for the first time the diversity of aphid pathogens and the spread of both pathogens and parasitoids with host dispersal flight in the low-latitude plateau.


Agar in the management of hyperbilirubinaemia in the premature baby.
Eighty low birthweight infants (1500 to 2500 g) were randomly assigned to a group given oral agar and a control group. The study was first performed in 24 agar-fed babies and 24 control babies. The treated infants received a daily total amount of 600 mg/kg of agar beginning at 12 hours of age, for 7 days. In the later stage of the trial, 16 agar-fed babies and 16 control babies were investigated. The total daily amount of agar was raised to 700 mg/kg, beginning at 6 hours of age for 7 days. No complications were observed with the administration of agar. Serum bilirubin levels were not significantly lower in the agar-fed infants. We conclude that agar supplemented feeding is not indicated in the management of hyperbilirubinaemia in low birthweight newborn infants.


Method for creating a three-dimensional magnetic null point topology with an accurate spine axis.
Three-dimensional magnetic null points (3D nulls) are sites of dynamic activity in a wide range of naturally-occurring and laboratory plasma environments. The topology of a 3D null is defined by a two-dimensional fan plane of radial field lines and a one-dimensional, collimated spine axis. Here, we build on previous work that was able to form an extended 3D null topology using an assembly of circular conducting coils, with each coil carrying a constant current. While that magnetic field design decayed from the mathematically pure form away from the central null, this paper introduces an algorithm for modulating the current through each coil to form a more mathematically pure spine axis along the entirety of the coil assembly. By the method of solving an inverse problem, we demonstrate that unique currents exist for any arbitrary distribution of axially-aligned circular coils for creating an accurate spine axis in a 3D null topology. Tests of this algorithm are performed on spherical, cylindrical, and cone-shaped coil assemblies. Vector magnetic field mapping of these small-scale demonstrators verifies that an accurate spine axis is maintained along the entire central axis of the coil assemblies. The magnetic field accuracy is roughly maintained along the fan plane but decays strongly toward the outer extents of the coils. The inverse method presented here is not limited to 3D null topologies but can be adapted to match any theoretical form of the magnetic field along a single axis.


[Ophthalmoscopy attempts before Helmholtz].
The principle of contact lens ophthalmoscopy was discovered in 1703; the fundus contact lens was very nearly invented in 1844. Coaxial illumination was applied in 1823 and improved in 1841 by including a mirror, while, the first usable ophthalmoscope was designed in 1847. This article pays tribute to the virtually ignored services of Méry, Kussmaul, Purkinje, Hofmann, and Babbage.


Phos-tag analysis of Rab10 phosphorylation by LRRK2: a powerful assay for assessing kinase function and inhibitors.
Autosomal dominant mutations that activate the leucine-rich repeat kinase 2 (LRRK2) cause inherited Parkinson's disease. Recent work has revealed that LRRK2 directly phosphorylates a conserved threonine/serine residue in the effector-binding switch-II motif of a number of Rab GTPase proteins, including Rab10. Here we describe a facile and robust method to assess phosphorylation of endogenous Rab10 in mouse embryonic fibroblasts (MEFs), lung and spleen-derived B-cells, based on the ability of the Phos-tag reagent to retard the electrophoretic mobility of LRRK2-phosphorylated Rab10. We exploit this assay to show that phosphorylation of Rab10 is ablated in kinase-inactive LRRK2[D2017A] knockin MEFs and mouse lung, demonstrating that LRRK2 is the major Rab10 kinase in these cells/tissue. We also establish that the Phos-tag assay can be deployed to monitor the impact that activating LRRK2 pathogenic (G2019S and R1441G) knockin mutations have on stimulating Rab10 phosphorylation. We show that upon addition of LRRK2 inhibitors, Rab10 is dephosphorylated within 1-2 min, markedly more rapidly than the Ser(935) and Ser(1292) biomarker sites that require 40-80 min. Furthermore, we find that phosphorylation of Rab10 is suppressed in LRRK2[S910A+S935A] knockin MEFs indicating that phosphorylation of Ser(910) and Ser(935) and potentially 14-3-3 binding play a role in facilitating the phosphorylation of Rab10 by LRRK2 in vivo The Rab Phos-tag assay has the potential to significantly aid with evaluating the effect that inhibitors, mutations and other factors have on the LRRK2 signalling pathway.


Microcystins: Biogenesis, Toxicity, Analysis, and Control.
Microcystins are cyclic peptide toxins formed by cyanobacteria. These toxins are recognized for their association with algal blooms, posing a significant threat to ecosystems and drinking water quality. Due to the growing environmental concerns they raise, a comprehensive review on microcystins' genesis, toxicity, and analytical methods for their quantitative determination is outlined. Genes, including the mcyABC cluster, regulate microcystin biogenesis. Bioanalytical experiments have identified key environmental factors, such as temperature and nitrogen availability, that promote microcystin production. Microcystin toxicity is explored based on its modulatory effects on protein phosphatases 1 and 2A in specific tissues and organs. Additionally, biochemical mechanisms of chelation, transportation, resultant oxidative stress, and tumor promotion abilities of microcystins are also discussed. Various analytical methods to separate, detect, and quantify microcystins, including the quantitative real-time polymerase chain reaction, enzyme-linked immunosorbent assay, nuclear magnetic resonance spectroscopy, and chromatographic platforms-linked tandem mass spectrometry (LC-MS) for unequivocal structural identification, are also reviewed. Since control of microcystins in water is of great necessity, both water treatment and mechanisms of abiotic transformation and microbial degradation are also discussed.


Generation of a T-cell hybridoma producing a contrasuppressor factor for contact sensitivity.
C3H/HeN mice were immunized to induce contrasuppressor T-cell (Tcs) activity, splenic T cells from these mice were fused with the BW5147 thymoma, and the resulting hybridomas were tested for their ability to produce a contrasuppressor T-cell factor (TcsF). Nine TcsF-producing hybridomas were preliminarily identified by their ability to inhibit the effect of antigen-specific suppressor T-cell factor (TsF) on the adoptive transfer of contact sensitivity. One of these hybrids, AF5.C6, was cloned, the production of a contrasuppressor factor confirmed, and the high-titred TcsF produced by this cloned hybrid characterized. Hybridoma-derived TcsF is antigen-specific and specifically binds its antigen, but does not bear immunoglobulin (Ig) determinants. Thus, hybridoma-derived TcsF is serologically and functionally identical to an antigen-specific contrasuppressor factor for contact sensitivity, whose production from splenocyte cell cultures has previously been described. The generation of a hybridoma secreting a contrasuppressor factor identical to that produced by spleen cells significantly strengthens the hypothesis that the phenomenon of T-cell contrasuppression is mediated by a specific subset of cells whose activity is contrasuppressive. The further advantages of employing T-cell hybridomas for functional, biochemical and molecular genetic analyses of contrasuppression are also discussed.


Point-of-care coagulation monitoring: first clinical experience using a paper-based lateral flow diagnostic device.
Vitamin K antagonists such as warfarin are the most widely used class of oral anticoagulants. Due to a narrow therapeutic window, patients on warfarin require regular monitoring. Self-testing using point-of-care (POC) diagnostic devices is available, but cost makes this monitoring method beyond reach for many. The main objective of this research was to assess the clinical utility of a low-cost, paper-based lateral flow POC diagnostic device developed for anticoagulation monitoring without the need for a separate electronic reader. Custom-fabricated lateral flow assay (LFA) test strips comprised of a glass fiber sample pad, a nitrocellulose analytical membrane, a cellulose wicking pad, and a plastic backing card were assembled in a plastic cassette. Healthy volunteers and patients on warfarin therapy were recruited for this prospective study. For each participant, a whole blood sample was collected via fingerstick to determine: (1) international normalized ratio (INR) using the CoaguChek® XS coagulometer, (2) hematocrit by centrifugation, and (3) red blood cell (RBC) travel distance on the experimental LFA device after 240 s using digital image analysis. RBC travel distance measured on the LFA device using blood samples obtained from warfarin patients positively correlated with increasing INR value and the LFA device had the capability to statistically distinguish between healthy volunteer INR values and those for patients groups with INR ≥ 2.6. From these data, it is predicted that this low-cost, paper-based LFA device can have clinical utility for identifying anticoagulated patients taking vitamin K antagonists who are outside of the desired therapeutic efficacy window.


Rapid purification of squirrel monkey retrovirus-H major gag protein by high performance liquid chromatography.
The major gag protein (p34) of squirrel monkey retrovirus-H was purified in one chromatographic step by anion-exchange high performance liquid chromatography. The virus in a crude fraction was disrupted with Brij 35 in the presence of three kinds of protease inhibitors. The soluble virus lysate was injected into a Polyanion SI column, and p34 was eluted with a linear salt gradient. The recovery of the protein was about 60%. The purified p34 was nearly homogenous as judged by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and silver staining.


Mental health and psychosocial support in response to onset of the COVID-19 pandemic: Emotional and Stress Management Intervention in Liberia, Sierra Leone, and Ivory Coast.
In response to the psychological distress experienced by people affected by the onset of the COVID-19 pandemic, Action Against Hunger (Action contre la Faim, ACF) developed and implemented the Emotional and Stress Management Intervention (ESMI) in Liberia, Sierra Leone, and Ivory Coast. ESMI is a person-to-person two-session, non-specialized, mental health and psychosocial support intervention for adults and adolescents in the general population based in problem solving therapy and principles of emotional regulation. Using de-identified programmatic data for each country, we conducted paired t-tests to assess whether adults and adolescents who received ESMI experienced changes in reported psychological distress and perceived social support following the intervention. We also performed pairwise correlations to test whether there were associations between changes in distress and social support over the course of participation in ESMI. Descriptive analyses were performed for presenting problems and coping strategies reported during the sessions. Mean scores for psychological distress at baseline and follow-up were significantly different in all countries: Sierra Leone (mean (m) = -6.11; 95% confidence interval (CI) = -6.25 to -5.96); Ivory Coast (m = -3.21; 95% CI = -3.33 to -3.10); and Liberia (m = -2.86; 95% CI = -3.15 to -2.56). Changes in perceived social support were also statistically significant for Sierra Leone (m = 6.87; 95% CI = 6.72-7.02); Ivory Coast (m = 3.12; 95% CI = 2.97-3.27); and Liberia (m = 1.13; 95% CI = 1.00-1.27). Correlations (r) between changes in distress and changes in social support varied by country, and ranged from negative in Liberia, (r = -0.88, P = 0.001), to positive in Ivory Coast (r = 55, P = 0.001), and null in Sierra Leone (r = -0.07, P = 0.11). Our findings show changes in psychological distress and perceived social support for participants who completed two sessions of ESMI, suggesting a potential benefit of ESMI as a person-to-person mental health and psychosocial support for individuals in distress affected by a pandemic. A future randomized controlled trial with a focus on key implementation factors (i.e., pre-testing visual analogue scales, treatment fidelity, and comparison of in-person vs remote) is recommended as next steps in research.


Gender-dependent effect of Gpbar1 genetic deletion on the metabolic profiles of diet-induced obese mice.
G-protein-coupled bile acid receptor 1 (GPBAR1/TGR5/M-Bar/GPR131) is a cell surface receptor involved in the regulation of bile acid metabolism. We have previously shown that Gpbar1-null mice are resistant to cholesterol gallstone disease when fed a lithogenic diet. Other published studies have suggested that Gpbar1 is involved in both energy homeostasis and glucose homeostasis. Here, we examine the functional role of Gpbar1 in diet-induced obese mice. We found that body weight, food intake, and fasted blood glucose levels were similar between Gpbar1-null mice and their wild-type (WT) littermates when fed a chow or high-fat diet (HFD) for 2 months. However, insulin tolerance tests revealed improved insulin sensitivity in male Gpbar1(-/-) mice fed chow, but impaired insulin sensitivity when fed a HFD. In contrast, female Gpbar1(-/-) mice exhibited improved insulin sensitivity when fed a HFD compared with their WT littermates. Female Gpbar1(-/-) mice had significantly lower plasma cholesterol and triglyceride levels than their WT littermates on both diets. Male Gpbar1(-/-) mice on HFD displayed increased hepatic steatosis when compared with Gpbar1(+)(/)(+) males and Gpbar1(-/-) females on HFD. These results suggest a gender-dependent regulation of Gpbar1 function in metabolic disease.


An SDI program for distributing funding opportunities using electronic mail.
As the competition for funding increases, the need to make researchers aware of all available funding is becoming more acute. The solution presented here is a Selective Dissemination of Information (SDI) service which electronically mails funding information that matches a researcher's keywords. The keywords are part of extensive faculty profiles that make up a Faculty Expertise database. The funding information comes from the Sponsored Programs Information Network (SPIN) database. The software enables researchers to learn about appropriate funding opportunities without spending time actively searching for them.


[Study on the relationship between blood stasis syndrome and clinical pathology in patients with IgA nephropathy].
To explore the relationship between blood stasis Syndrome and clinical pathological parameters in patients with IgA nephropathy (IgAN). The clinicopathological data were analyzed of 94 IgAN patients of traditional Chinese medicine blood stasis syndrome. Of the 94 IgAN patients, 61.70% had blood stasis syndrome (BS) and 38.30% had non- blood stasis syndrome (non-BS). In patients with BS, dark purple tongue proper was the symptom most commonly seen; the clinical manifestations were mostly proteinuria with hematuria, often accompanied with hypertension and renal dysfunction. Compared with those in patients without BS, plasma levels of serum creatinine (SCr), triglyceride (TG) and plasma fibrinogen (FIB) were obviously higher, activated partial thromboplastin time (APTT), and urokinase-type plasminogen activators (u-PA) significantly lower; and scores of glomerular sclerosis, tubular interstitial lesions, interstitial inflammatory cell infiltration, interstitial fibrosis, tubular atrophy and vascular sclerosis significantly higher. Besides, the Lee's grades in them of III - V were mostly seen. Blood stasis syndrome of IgAN are correlated with certain clinical parameters and severity of renal pathological changes. The combination of TCM holistic syndrome differentiation and modern medicinal micro-differentiation is more favorable for making clear the nature of blood stasis Syndrome of IgAN.


[Interrelations of pineal gland morpho-functional indices and immune system organs in rats exposed to natural illumination regime and continuous illumination].
The objective of this investigation was to determine the complex response of the pineal gland (PG) and of the organs of the immune system in Wistar rats in response to a violation of the illumination regime in the experiment. Animals were kept under natural light regime and continuous illumination for 14 days. After that rats were sacrificed and the mass of the body, PG, gonads, thymus and spleen was measured. Thymus and spleen cell subpopulations were determined by flow cytometry. The lipofuscin content in PG was determined by measuring an autofluorescence intensity in frozen tissue sections in the wavelength range of 505-545 nm using a confocal laser scanning microscope LSM 510 META (Carl Zeiss). The correlation analysis showed an increase in the amount and the change of sign and direction of relations between the indices of the state of PG and the immune system. This indicates the up-regulation of the intensity of inter-system relationships and the change of migration and differentiation vector of immunocompetent cells.


Chlorpromazine-induced electrocardiogram abnormalities.
The aim of our clinical investigation was to evaluate the electrocardiographic abnormalities in patients receiving only chlorpromazine, and to assess the role of sex, age and length of illness in these abnormalities. 96 schizophrenic patients (48 male and 48 female patients) satisfying study criteria were selected for inclusion and changed from their old medication to a fixed dose of 125 mg chlorpromazine daily. This uniformization period lasted two weeks, during which the electrocardiograms were taken after an overnight fast. Five patients were excluded because their electrocardiographic changes revealed the possibility of an organic heart disease. The electrocardiograms were found to be normal for 65.9% of the patients and abnormal for 34.1%. 11% of patients were classified as demonstrating Grade I repolarization abnormalities, 14.3% of patients as Grade II, and 8.8% as Grade III. Chi square (X2) tests revealed no significant differences between sexes, age groups or lenghts of illness as regards ECG normality and grade of abnormality.


[The reception of Heinz Kohut in Germany].
First the discussion of Kohut's new ideas in the United States is sketched as a background. The response to these ideas was divided: on the one hand they were hailed as important innovations of psychoanalytic theory, and a circle of colleagues formed around their author; on the other hand they were violently rejected, and old friends distanced themselves from him. In Germany Kuhut's ideas were initially well received. His visits, lectures and supervisions resulted in a lively exchange and a number of friendships. When the differences between Kohutian and classical theory became evident this led increasingly to disillusionment and retreat. De-emphasizing drive and ego psychology had considerable consequences for psychoanalytic technique as well as for the analyst's Menschenbild, his relationship to the patient and his critical self-reflection. In Germany, too, a circle of colleagues emerged, following and elaborating the ideas of Kohut.


Sex differences in cognition and their relationship to male mate choice.
Male cognition has gained recognition as an important potential player in sexual selection. A number of studies have found positive correlations between male sexual signals and cognitive performance and/or female preferences for males with better cognitive performance, although other studies have not found these relationships. Sex roles can differ dramatically, and sex differences in selection on cognition likely follow from the different tasks associated with these sex roles. Here, using threespine stickleback Gasterosteus aculeatus, a species with clearly divergent sex roles and mutual mate choice, we focus on the cognitive trait inhibitory control because males must differentially respond to reproductive females versus other sticklebacks while defending territories and refrain from eating eggs and fry while performing paternal care. We presented fish with a detour task four times over a period of 7 days, allowing us to assess initial inhibitory control and improvement over time. We ask 1) whether there are sex differences in inhibitory control and 2) whether male mate choice is associated with female inhibitory control. Although males outperformed females on three different measures of detour task performance across four trials, these differences were largely explained by males being less neophobic than females. Females took more trials to successfully solve the detour task, even after accounting for sex differences in neophobia. Female cognitive abilities, however, were unrelated to the vigor with which males courted them. The equivocal results regarding sex differences in cognitive ability suggest further study given the very different selection pressures each sex experiences.


Use of a bDMARD or tsDMARD for the management of inflammatory arthritis under checkpoint inhibitors: an observational study.
There is limited experience regarding the use of biological disease-modifying antirheumatic drug (bDMARD) and JAK inhibitor (JAKi) for the management of immune checkpoint inhibitors (ICI)-induced inflammatory arthritis. We aimed to assess their efficacy and safety in this setting. Using the Club Rhumatismes and Inflammation French network, we conducted a multicentre, retrospective, observational study of patients with cancer diagnosed with inflammatory arthritis under ICI(s) and treated with bDMARD or JAKi. Clinical data were collected using a standardised case report form. Twenty patients (60% men, median age 69.5 years) were included, with rheumatoid arthritis (RA)-like (n=16), polymyalgia rheumatica-like (n=2) or psoriatic arthritis-like (n=2) clinical presentation. Two patients had pre-existing RA. 90% were treated with glucocorticoids as first-line therapy and 60% received methotrexate prior to bDMARD or JAKi. Anti-interleukin-6 receptor (IL-6R) therapy was used in 13/20 patients (65%), leading to clinical improvement in 11/13 patients (85%), but one patient experienced intestinal perforation and cancer progression was noticed in 6/13 patients (46%). Tumour necrosis factor inhibitors were used in 5/20 patients (25%), with improvement in 4/5 patients (80%) and cancer progression was observed in 3/5 patients (60%). Two infections (diverticulitis and pneumonitis) were reported. Anakinra, baricitinib and ustekinumab were each used in one patient. Median duration of the bDMARD or JAKi was 17 weeks. Anti-IL-6R therapy is currently the most common strategy in patients with ICI-induced inflammatory arthritis and insufficient response to glucocorticoids and methotrexate, leading to improvement in >80%. Overall, cancer progression occurred in about half of patients and whether the bDMARD/JAKi impacted the tumour response remains to be determined.


Chick feed technique versus standard chop technique in micro incision cataract surgery.
The important factor for improving the cataract surgery is reduction in size of corneal incision. Small incision results in less induced astigmatism, and faster visual rehabilitation. An analysis of 100 eyes of 80 patients operated for phacoemulsification through micro incision by standard chop technique (50 eyes) in group-I, and chick feed technique (50 eyes) in group-II is presented. All of the patients were operated on by posterior limbal corneal incision under topical or sub-tenon anesthesia. In all patients, posterior chamber bag fixation foldable intraocular lens implantation was performed through 1.4 to 1.6 mm corneal incision. Forty patients (80%) out of fifty operated in group-2 had an over all visual recovery of 6/12 to 6/9 on day one post operative, as compared to group-1 where only ten (20%) patients out of fifty had visual recovery of 6/12 to 6/9. In the second week, out of 37 patients operated in group-2, thirty patients (81%) had visual acuity 6/6. Similarly in second week post operative, out of forty three patients operated in group-1, only eighteen patients (41.8%) had V/A of 6/6. Maximum visual recovery was observed in early post operative phase in group-2 patients. The chick feed technique has been proved to be the most compromising method in micro incision cataract surgery, as compared to standard chop method, due to its capability of working on low energy and negligible vacuum.


Demographic and Clinical Features of Thyroid Carcinomas in Republic of Macedonia (1999-2010).
Thyroid carcinomas (TC) are the most common endocrine malignancies. In some parts of the world, the incidence of TCs has increased over the past few decades, especially in females according to some studies. We have set as the objective for our study to analyse the demographic, ultrasound features, thyroid hormonal status and frequency of thyroid carcinomas in the Republic of Macedonia according to histopathological type. Retrospective analysis of medical data from all diagnosed and treated patients with TC at the Institute of Pathophysiology and Nuclear Medicine for the period 1999-2010 was performed. Demographic characteristics: age at diagnosis, gender, histopathological type of TC and from clinical features: US findings and thyroid hormonal state at initial examination and their distribution in eight state regions were evaluated. Total number of 204 patients with TC in the Republic of Macedonia was registered. Papillary thyroid carcinoma (PTC) was the most frequent with 131 pts (64.21%), follicular (FTC) with 13 pts (6.37%) was second thyroid malignoma, followed by medullary (MTC) with 12 pts (5.88%), anaplastic (ATC) 11 pts (5.39%) and the rarest types were Hurtle cell carcinoma and intrathyroid sarcoma with only 1 diagnosed case. Age varied widely from 7 yrs to 88 yrs age (average 47.9 ± 16.6 yrs). PTC was more prevalent in younger age groups, while ATC was diagnosed in elderly patients. In all of the eight-country regions, the prevalence rate was higher for females than males (3:1) or 15.21/105 female to 5.03/105 male prevalence rate. According to US appearance mostly TC was unilateral in 42.65% and multifocal in 7.84% with dimensions from 15 to 50 mm. There is an increase in incidence and prevalence rate of TCs in our country, mostly PTC, while reduction exists in the number of diagnosed cases of ATC and FTC, comparing with previous studies before iodine prophylaxis program. Different from described in the literature is female: male (4:1) ratio for ATC. According to US features, we can conclude that introduction of more detailed reporting system may improve diagnostic accuracy.


[Conrad Ferdinand Meyer reflected in the paradigm change in German psychiatry].
German-speaking psychiatrists had a great interest in the Swiss poet and writer Conrad Ferdinand Meyer (1825-1898)-even after his death. Meyer was hospitalised twice for major depression with psychotic features. For many years of his life he showed a chronic depressive disorder. We would diagnose a dysthymic disorder with comorbid recurrent major depressive disorder with psychotic features according to DSM-IV or ICD-10. After Meyer had lived isolated for many years and had hardly left his house, he reached public recognition and found his "profession" only at the age of 40. Different pathographic publications (amongst others Möbius, Hellpach, Sadger, Lang, Jung) on Meyer in the early 20th century reflect the debate over both Kraepelin's theories and psychoanalysis. In these publications the scientific argument was often more important than Meyer's biography. Two topics play an important role in these discussions: the differences between idiographic and nomothetic method, and the question, where the border between "personality variation" and "illness" lies.


Severe recurrent rhabdomyolysis-induced acute kidney injury in a HIV-infected patient on antiretroviral therapy.
Antiretroviral medications, specifically tenofovir, have been linked to acute tubular necrosis in humans with a suggested mechanism of direct tubular injury. Rhabdomyolysis has rarely been described in patients on highly active antiretroviral therapy (HAART). To the best of our knowledge, severe recurrent rhabdomyolysis-induced acute kidney injury (AKI) in a HIV-infected patient on two different triple antiretroviral regimens has not been reported. We present a HIV-positive patient who first developed heme pigment-induced oliguric AKI due to non-traumatic rhabdomyolysis, 5 days after initiation of triple antiretroviral therapy. Renal function normalized 2 months after discontinuation of antiretroviral therapy. Two weeks after reinitiating a different HAART regimen, our patient developed a recurrent episode of severe rhabdomyolysis-induced AKI. Both rhabdomyolysis and AKI resolved after discontinuation of the second antiretroviral regimen. First tenofovir and subsequently abacavir seem to be the likely culprits in our case. We also briefly discuss tenofovir nephrotoxicity followed by a literature review on rhabdomyolysis in HIV-infected patients.


Pseudoaneurysm of the renal artery following partial nephrectomy: imaging findings and coil embolization.
To present the imaging findings of five patients with renal artery pseudoaneurysm (RAP) after partial nephrectomy. Five patients (four men and one woman) with RAP as a complication of partial nephrectomy were studied. The diagnosis of RAP was established using contrast-enhanced computed tomography (CT) in three patients and renal angiography in two patients. In two cases, the diagnosis was evident on ultrasound with colour Doppler. The indication for partial nephrectomy (open approach in four patients and laparoscopic in one patient) was a space-occupying lesion, which proved to be a renal cell carcinoma. All patients presented with macroscopic haematuria, 1-21 days (mean 12.2 days) after surgery. In three of patients the definitive diagnostic imaging method was contrast-enhanced CT. The arterial phase of CT showed a well-circumscribed dense collection of contrast material located within the renal parenchyma. In two other patients the initial and conclusive diagnostic imaging method was renal angiography. All patients underwent selective renal angiography with therapeutic coil embolization. The procedure failed in one patient, which necessitated nephrectomy. Pseudoaneurysm of the renal artery should be considered in patients presenting with macrohaematuria after nephron-sparing surgery. The diagnosis can be established using contrast-enhanced CT, ultrasound with colour Doppler, or angiography. Renal angiography with selective embolization is a safe and efficacious technique for managing the condition.


Fibronectin-mediated adhesion rescues cell cycle arrest induced by fibroblast growth factor-1 by decreased expression of p21(cip/waf) in human chondrocytes.
In chondrocytes, fibroblast growth factors (FGFs) inhibit chondrocytes proliferation by upregulation of the cell cycle inhibitor p21(cip/waf). In this report, we first investigated the roles of fibronectin (FN)-mediated cell adhesion in the modulation of FGF-1's antiproliferative function in chondrocytes. In this study, we found that FN-mediated signaling could rescue cell cycle arrest induced by FGF-1 in primary human chondrocytes. This prevention of cell cycle arrest induced by FGF-1 was due to the suppression of the cell cycle inhibitor p21(cip/waf) expression on adhesion to FN and its downstream activation of signaling pathways. Finally, we showed that this rescue induced by FN-mediated adhesion is dependent on the extracellular regulated kinase (ERK) signaling pathway. Taken together, these studies support that, despite FGF-FGF receptor's growth-inhibitory function, the FN-mediated signaling can collaborate to compensate for its negative effect on chondrocytes proliferation, providing evidence for cross talk between signals emerging from these cell surface molecules in chondrocyte.


Knee complaints and consequences on work status; a 10-year follow-up survey among floor layers and graphic designers.
The purpose of the study was to examine if knee complaints among floor layers predict exclusion from the trade. In 1994/95 self-reported data were obtained from a cohort of floor layers and graphic designers with and without knee straining work activities, respectively. At follow-up in 2005 the questionnaire survey was repeated. The study population consisted of 81 floor layers and 173 graphic designers who were presently working in their trades at baseline (1995). All participants were men aged 36-70 years in 2005. We computed the risk of losing gainful employment in the trade according to occurrence of knee complaints at baseline, using Cox proportional hazard regression adjusted for a number of potential confounding variables. Moreover, the crude and adjusted odds risk ratio for knee complaints according to status of employment in the trade were computed, using graphic designers as reference. A positive but non-significant association between knee complaints lasting more than 30 days the past 12 months and exclusion from the trade was found among floor layers (Hazard Ratio = 1.4, 95% CI = 0.6-3.5).The frequency of self-reported knee complaints was lower among floor layers presently at work in the trade in year 2005 (26.3%) compared with baseline in 1995 (41.1%), while the opposite tendency was seen among graphic designers (20.7% vs. 10.7%). The study suggests that knee complaints are a risk factor for premature exclusion from a knee demanding trade. However, low power of the study precludes strong conclusions. The study also indicates a healthy worker effect among floor layers and a survivor effect among graphic designers.


A rare cause of upper airway obstruction: spontaneous synchronous sublingual and laryngeal haematomas.
Anticoagulation with warfarin is commonly used for prevention of thromboembolic events in patients with atrial fibrillation. Bleeding is the main side effect of anticoagulation. We report the case of a 66-year-old man who developed two spontaneous synchronous upper airway haematomas while on warfarin therapy. To our knowledge, this is the first reported case of a sublingual haematoma presenting simultaneously with supraglottic laryngeal haematomas. Upper airway haematomas are rare in the absence of a history of trauma but need to be urgently assessed due to their life-threatening potential. Clinicians should be aware of the possibility of haematomas involving the upper airway in patients on anticoagulant therapy, particularly if complaining of red flag symptoms such as acute onset dysphonia, odynophagia or airway/breathing difficulties.


Transgenic animals: current and alternative strategies.
Transgenic animal technology is one of the most fascinating technologies developed in the last two decades. It allows us to address questions in life sciences that no other methods have achieved. The impact on biomedical and biological research, as well as commercial interests are overwhelming. The questions accompanying this fast growing technology and its diversified applications attract the attention from a variety of entities. Still, one of the most fundamental problems remaining is the search for an efficient and reliable gene delivery system for creating transgenic animals. The traditional method of pronuclear microinjection has displayed great variability in success among species. While an acceptable efficiency in the production of transgenic mice has been attained, the relative low efficiency (<1%) in creating transgenic livestock has become one of the barriers for its application. In the past decades, improvements in producing transgenic livestock have made a slow progression, however, the recent advancement in cloning technology and the ability to create transgenic livestock in a highly efficient manner, have opened the gate to a new era in transgenic technology. Discoveries of new gene delivery systems have created an enthusiastic atmosphere that has made this technology so unique. This review focuses on gene delivery strategies as well as various approaches that may assist the advancement of transgenic efficiency in large animals.


Short-term effectiveness of intravitreal bevacizumab vs. ranibizumab injections for patients with polypoidal choroidal vasculopathy.
To compare the effectiveness of intravitreal injections of bevacizumab and ranibizumab in patients with treatment-naive polypoidal choroidal vasculopathy (PCV). Records from 106 consecutive patients who received intraviteral bevacizumab (n = 58, 1.25 mg) or ranibizumab (n = 52, 0.5 mg) for treatment of PCV were retrospectively reviewed. After three initial monthly loading injections, injection was performed as needed. The main outcome measures included best-corrected visual acuity (BCVA), foveal central thickness (FCT) as assessed by spectral domain optical coherence tomography, and the changes in polypoidal lesions based on an indocyanine green angiography. The average number of injections was 3.31 ± 1.25 in the bevacizumab group and 3.44 ± 0.92 in the ranibizumab group. Mean logarithm of the minimum angle of resolution of BCVA from baseline to 6 months after injection improved by 0.17 in the bevacizumab group (p = 0.03) and by 0.19 in the ranibizumab group (p = 0.01). Average FCT decreased from 322 ± 62.48 µm to 274 ± 40.77 µm in the bevacizumab group (p = 0.02) and from 338 ± 50.79 µm to 286 ± 36.93 µm in the ranibizumab group (p = 0.02). Polyp regression rate was 20.7% (12 of 58 eyes) in the bevacizumab group and 21.2% (11 of 52 eyes) in the ranibizumab group. There was no statistically significant difference between groups in BCVA improvement achieved, FCT improvement achieved, and polyp regression rate between groups. Intravitreal injections of bevacizumab and ranibizumab have similar effects in stabilizing of visual acuity, macular edema, and regression of polypoidal complex in PCV eyes over the short term.


In Situ Detecting Thermal Stability of Solid Electrolyte Interphase (SEI).
Solid electrolyte interphase (SEI) plays an important role in regulating the interfacial ion transfer and safety of Lithium-ion batteries (LIBs). It is unstable and readily decomposed releasing much heat and gases and thus triggering thermal runaway. Herein, in situ heating X-ray photoelectron spectroscopy is applied to uncover the inherent thermal decomposition process of the SEI. The evolution of the composition, nanostructure, and the released gases are further probed by cryogenic transmission electron microscopy, and gas chromatography. The results show that the organic components of SEI are readily decomposed even at room temperature, releasing some flammable gases (e.g., H2 , CO, C2 H4 , etc.). The residual SEI after heat treatment is rich in inorganic components (e.g., Li2 O, LiF, and Li2 CO3 ), provides a nanostructure model for a beneficial SEI with enhanced stability. This work deepens the understanding of SEI intrinsic thermal stability, reveals its underlying relationship with the thermal runaway of LIBs, and enlightens to enhance the safety of LIBs by achieving inorganics-rich SEI.


Modern trends in internal fixation of femoral shaft fractures in children. A critical review.
Elastic intramedullary (IM) devices, which avoid the physeal region like Nancy and Ender nails do, can be used in children younger than even 4 years without compromising the trochanter physis or risking an avascular necrosis. Intramedullary fixation of femoral shaft fractures leads to satisfactory results of alignment and union. Prerequisites for intramedullary closed nailing are a traction table, especially for older children and adolescents, and an image intensifer. Interlocking IM, Ender, and Nancy nails all have the equal advantage of early weight bearing and reduced hospitalization time compared with traction and cast management. Küntscher or interlocking nails should only be used in adolescents close to the end of growth to avoid growth arrest of the trochanterocervical physis. Küntscher nails and interlocking IM nails are both associated with the small but troublesome risk of avascular necrosis. Ender and Nancy nails, with retrograde or antegrade pinning, have a low complication rate and a short learning curve for surgeons. Overgrowth in late controls after IM rodding of shaft fractures is about the same as the other types of treatment with an average overgrowth of 7 mm. Short hospital stay for children with IM nails reduces cost of treatment to about one half compared with in-hospital traction and cast management.


Chrysin ameliorates cerebral ischemia/reperfusion (I/R) injury in rats by regulating the PI3K/Akt/mTOR pathway.
In this study, the effects of chrysin on cerebral ischemia by establishing middle cerebral artery occlusion (MCAO) in rat were investigated. In vivo experiments, the rats were orally administrated with clopidogrel or chrysin once daily for 7 days before the experimental of ischemia and the rats were divided into 5 groups: the sham group, the I/R group, I/R + clopidogrel group, I/R + chrysin (10 mg/kg), I/R + chrysin (20 mg/kg) group. Chrysin significantly ameliorated the I/R rats, evaluated by TTC staining, determination of brain wet to dry weight ratio and neurological deficits. Moreover, in serum and brain tissues of the I/R rats, chrysin also could effectively suppress the release of inflammatory cytokines, including levels of interleukin-6 (IL-6), interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). In addition, chrysin could improve the SOD activity in the I/R rats. Mechanically, chrysin could activate the PI3K/Akt/mTOR pathway, inhibited inflammation and apoptosis. In oxygen-glucose deprivation and recovery (OGD/R)-induced SH-SY5Y cells in vitro. Chrysin markedly decreased the levels of TNF-α, IL-6 and IL-1β in supernatant of OGD/R-induced SH-SY5Y cells via activating PI3K/Akt/mTOR pathway. In conclusion, our study demonstrated that chrysin might be a potential therapeutic agent for cerebral ischemia.


Glycated hemoglobin level is strongly related to the prevalence of carotid artery plaques with high echogenicity in nondiabetic individuals: the Tromsø study.
High levels of HbA1c have been associated with increased mortality and an increased risk of atherosclerosis assessed as carotid intima-media thickness or plaque prevalence. In the present population-based study, we examined the association between HbA1c and plaque prevalence with emphasis on plaque echogenicity in subjects not diagnosed with diabetes. HbA1c measurements and ultrasonography of the carotid artery were performed in 5960 subjects (3026 women, 2934 men) 25 to 84 years of age. Plaque morphology was categorized into 4 groups from low echogenicity (soft plaque) to strong echogenicity (hard plaque). HbA1c was categorized into 5 groups: <5.0%, 5.0% to 5.4%, 5.5% to 5.9%, 6.0% to 6.4% and >6.4%. Carotid plaque prevalence increased with increasing HbA1c level (P for linear trend=0.002). The OR for hard plaques versus no plaques was 5.8 in the highest HbA1c group (>6.4%) compared with subjects in the lowest group (<5.0%) after adjustment for several possible confounders. The risk of predominantly hard plaques was also significantly associated with HbA1c levels, although the ORs at each level were somewhat lower than for hard plaques. With respect to the risk of soft plaques versus no plaques, no statistically significant relationship with HbA1c levels was found. Metabolic changes reflected by HbA1c levels may contribute to the development of hard carotid artery plaques, even at modestly elevated levels.


Identification and genotype related classification of children with long QT-syndrome using 24 h Holter recordings.
The long QT syndrome (LQTS) belongs to the family of hereditary diseases and can cause life-threatening arrhythmias and leads to sudden cardiac death. Mutations on six genes are responsible for changes in the electrophysiological properties of myocardial cells that are involved in the repolarization phase. In the surface ecg this is expressed by a prolonged QT interval and genotypespecific shapes for the T-Wave. The aim of the study was to find parameters that quantify properties of the repolarization phase which can be used in addition to the established Schwartz score in the process of diagnosing LQTS. Furthermore, ecg features were evaluated for the separation of the LQT subtypes LQT1, LQT2 and LQT3. The combination of the features PtA50 and QTc yielded with 93% sensitivity and 100% specificity the best results in the field of patient identification. Despite the small dataset consisting of 14 patients that was available for the second aim, the achieved results for the morphology indices motivate further research in this field.


Suicide and COVID-19: a rapid scoping review.
There is considerable interest in exploring effects of coronavirus disease 2019 (COVID-19) pandemic on mental health. Suicide is one of the leading causes of mortality worldwide and changes in daily life brought by the pandemic may be additional risk factors in people with pre-existing mental disorders. This rapid PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews) scoping review aims to identify and analyze current evidence about the relation between COVID-19 pandemic outbreak, along with COVID-19 disease and severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) infection, and suicide in individuals with previously diagnosed mental disorders. First, we conducted a comprehensive review of the literature, then proceeded to discuss findings in a narrative way. Tables were constructed and articles sorted according to the studies' methodologies. 53 papers were eventually identified as eligible, among which 33 are cross-sectional studies, 9 are longitudinal studies, and 11 studies using other methodologies. Despite suffering from a mental disorder is a risk factor for suicidal behavior per se, the advent of COVID-19 pandemic may exacerbate this relation. Nevertheless, data addressing a clear correlation between suicidal behavior and the pandemic outbreak are still controversial. Longitudinal analysis using validated suicide scales and multicenter studies could provide deeper insight and knowledge about this topic.


DUSP5 is methylated in CIMP-high colorectal cancer but is not a major regulator of intestinal cell proliferation and tumorigenesis.
The ERK signalling pathway regulates key cell fate decisions in the intestinal epithelium and is frequently dysregulated in colorectal cancers (CRCs). Variations in the dynamics of ERK activation can induce different biological outcomes and are regulated by multiple mechanisms, including activation of negative feedback loops involving transcriptional induction of dual-specificity phosphatases (DUSPs). We have found that the nuclear ERK-selective phosphatase DUSP5 is downregulated in colorectal tumours and cell lines, as previously observed in gastric and prostate cancer. The DUSP5 promoter is methylated in a subset of CRC cell lines and primary tumours, particularly those with a CpG island methylator phenotype (CIMP). However, this epigenetic change alone could not account for reduced DUSP5 expression in CRC cells. Functionally, DUSP5 depletion failed to alter ERK signalling or proliferation in CRC cell lines, and its transgenic overexpression in the mouse intestine had minimal impact on normal intestinal homeostasis or tumour development. Our results suggest that DUSP5 plays a limited role in regulating ERK signalling associated with the growth of colorectal tumours, but that methylation the DUSP5 gene promoter can serve as an additional means of identifying CIMP-high colorectal cancers.


Real-world relationship of early end points to survival end points in patients with resectable non-small-cell lung cancer.
Aim: Pathologic response has been shown to be a promising surrogate for survival in non-small-cell lung cancer. We examined the real-world relationship between these end points in patients with resectable stage IB-IIIA non-small-cell lung cancer receiving neoadjuvant chemotherapy/chemoradiotherapy (CT/CRT). Methods: Electronic health records/medical charts were analyzed. Overall and event-free survival (OS/EFS) were assessed by Kaplan-Meier stratified by pathologic response. Associations between the end points were assessed by Cox analyses. Results: A total of 425 patients were selected for the study; 147 and 278 received CT and CRT, respectively. Pathologic complete response (pCR) was associated with longer OS (adjusted HR = 0.50; 95% CI: 0.29-0.85) and EFS (adjusted HR = 0.44; 95% CI: 0.28-0.68) versus no pCR, and EFS was associated with OS (HR = 0.51, 95% CI: 0.38, 0.69). Conclusion: In patients receiving neoadjuvant CT/CRT, pCR and EFS were associated with improved survival in this real-world dataset.


Environmental exposure to cadmium, forearm bone density, and risk of fractures: prospective population study. Public Health and Environmental Exposure to Cadmium (PheeCad) Study Group.
Chronic low-level exposure to cadmium may promote calcium loss via urinary excretion. We undertook a prospective population study to investigate whether environmental exposure to cadmium lowers bone density and increases risk of fractures. We measured urinary cadmium excretion, a biomarker of lifetime exposure, in people from ten districts of Belgium, of which six districts bordered on three zinc smelters. We also measured cadmium in soil and in vegetables from the districts, and collected data on incidence of fractures and height loss. Bone density was measured at the forearm just above the wrist by single photon absorptiometry, and calculated as the mean of six proximal and four distal scans. Mean cadmium excretion at baseline was 8.7 nmol daily. Across the ten districts, mean cadmium concentration in soil ranged from 0.8 to 14.7 mg/kg, and from 0.1 to 4.0 mg/kg dry weight in vegetables. Median follow-up was 6.6 years. Mean forearm bone density in proximal and distal scans was 0.54 g/cm2 and 0.43 g/cm2 in men, and 0.44 g/cm2 and 0.34 g/cm2 in women. In postmenopausal women, a twofold increase in urinary cadmium correlated with 0.01 g/cm2 decrease in bone density (p<0.02). The relative risks associated with doubled urinary cadmium were 1.73 (95% CI 1.16-2.57; p=0.007) for fractures in women and 1.60 (0.94-2.72, p=0.08) for height loss in men. Cadmium excretion in districts near smelters was 22.8% higher (p=0.001) than in other districts, with fracture rates of 16.0 and 10.3 cases per 1000 person-years, respectively, and a population-attributable risk of 35.0%. Even at a low degree of environmental exposure, cadmium may promote skeletal demineralisation, which may lead to increased bone fragility and raised risk of fractures.


Comparison of methods for rotavirus detection in water and results of a survey of Jerusalem wastewater.
Methods for the detection of viable rotaviruses and rotavirus antigen in water were developed and compared. The methods included laboratory-developed enzyme-linked immunosorbent assays (ELISAs) with chromogenic and luminescent substrates, commercial Rotazyme and Enzygnost ELISAs, and an indirect immunofluorescent assay. Of the methods tested, the immunofluorescent assay and the Enzygnost ELISA were the most sensitive for the simian rotavirus SA-11. All of the methods were positive for human rotavirus from clinical specimens. Seeded SA-11 rotavirus was concentrated from water by absorption to and elution from Zeta Plus filters followed by organic flocculation. Interference with the assays by components of the wastewater concentrates was minimal for the ELISAs, although the undiluted organic flocs were cytotoxic for the immunofluorescent assay. A survey of Jerusalem wastewater was carried out over the course of 1 year, and samples were assayed for rotaviruses and enteroviruses. Although enteroviruses were found in almost all of the samples, all samples were negative for rotaviruses. The concentration of rotaviruses in the wastewater was thus below the detection limit of the method used.


Controlling the Topological Sector of Magnetic Solitons in Exfoliated Cr_{1/3}NbS_{2} Crystals.
We investigate manifestations of topological order in monoaxial helimagnet Cr_{1/3}NbS_{2} by performing transport measurements on ultrathin crystals. Upon sweeping the magnetic field perpendicularly to the helical axis, crystals thicker than one helix pitch (48 nm) but much thinner than the magnetic domain size (∼1 μm) are found to exhibit sharp and hysteretic resistance jumps. We show that these phenomena originate from transitions between topological sectors with a different number of magnetic solitons. This is confirmed by measurements on crystals thinner than 48 nm-in which the topological sector cannot change-that do not exhibit any jump or hysteresis. Our results show the ability to deterministically control the topological sector of finite-size Cr_{1/3}NbS_{2} and to detect intersector transitions by transport measurements.


Ten recommendations for reducing the long-term costs of conduct problems: A commentary on the economic analysis of Goulter et al. (2023).
The economic analysis of Goulter et al. (2023) identifies the long-term financial costs arising from conduct problems in the kindergarten period, including those associated with later criminal activity, lost offender productivity, victim costs and government and medical services. These costs are substantial and provide policymakers with a compelling argument for investing in early intervention and prevention of conduct problems. The ultimate goal of reducing the long-term costs of early conduct problems is likely to be achieved only through the coordinated efforts of many stakeholders and diverse courses of action. Outlined here are 10 recommendations for investment that in my view would support progress towards this outcome.


The dynamics of cardiac defense: from attention to action.
The attentional and motivational significance of cardiac defense is examined in two studies. In Study 1, cardiac defense was evoked by an intense acoustic stimulus in the context of either a visual search or a memory search task using letters as stimuli. Results showed a potentiation of the long latency acceleration of cardiac defense in the visual search task. In Study 2, participants performed the same visual search task using pleasant, neutral, and unpleasant pictures as stimuli. Results showed a further potentiation of the long latency acceleration of cardiac defense when the visual search task was performed with unpleasant, compared to pleasant or neutral pictures. These results indicate that cardiac defense has both attentional and motivational contributions, where the attentional significance is related to increased sensory processing, whereas the motivational significance is associated with preparation for active defense.


Connected Health in Hypertension Management.
e-health is defined as the use of communication and information technologies (ICT) to manage patients and their health in a more efficient way, with the aim of improving the overall quality of care. Healthcare services relying on telehealth (or telemedicine) and mobile health (m-health) are the most popular e-health tools used by healthcare professionals and consumers. These applications allow the exchange of medical data between patients and their doctors or among healthcare professionals, mainly through the Internet, and are used to provide healthcare services remotely (so-called "connected health"). The most popular telemedicine application in the field of hypertension is blood pressure telemonitoring (BPT), which enables transmission of BP and various clinical information from patients' homes or from the community to the doctor's surgery or the hospital. Numerous randomized controlled trials have documented a significant BP reduction combined with an intensification and optimization of the use of antihypertensive medications in patients making use of BPT plus remote counseling by a case manager, with the supervision of a doctor or a community pharmacist (telepharmacy). The major benefits of BPT are usually observed in high-risk patients. BPT can also be based on m-health wireless solutions, provided with educational support, medication trackers and reminders, and teleconsultation. In this context, BPT may favor patient's self-management, as an adjunct to the doctor's intervention, and foster patient's participation in medical decision making, with consequent improvement in BP control and increase in medication adherence. In conclusion, e-health solutions, and in particular telemedicine, are increasingly attaining a key position in the management of the hypertensive patient, with an enormous potential in terms of improvement of the quality of the delivered care, increase in the chance of a successful BP control and effective prevention of cardiovascular diseases.


Different gradients for neurotransmitter metabolites and protein in horse cerebrospinal fluid.
The serotonin metabolite, 5-hydroxyindoleacetic acid (5-HIAA) and the dopamine metabolite, homovanillic acid (HVA) in the cerebrospinal fluid (CSF) of seven clinically normal horses were evaluated with reverse phase high pressure liquid chromatography and electrochemical detection. Comparisons of the neurotransmitter metabolite concentrations were made on CSF collected simultaneously from the atlanto-occipital and lumbosacral regions. There were significantly higher amounts of 5-HIAA and HVA in atlanto-occipital CSF than in lumbosacral CSF. Mean 5-HIAA concentrations in atlanto-occipital and lumbosacral CSF were 206.1 +/- 37.0 nmol/L and 68.5 +/- 12.6 nmol/L, respectively. The mean HVA concentration in atlanto-occipital CSF was 254.4 +/- 50.4 nmol/L. No HVA was detected in lumbosacral CSF. In contrast, significantly greater protein concentrations were present in lumbosacral CSF than in atlanto-occipital CSF. Lumbosacral and atlanto-occipital CSF contained 32.1 +/- 3.7 mg protein/dl and 25.0 +/- 1.3 mg protein/dl, respectively. Thus, between the atlanto-occipital and lumbosacral space of the horses, a rostrocaudal gradient existed for neurotransmitter metabolites and a caudorostral gradient existed for protein.


Nanostructured silicon particles for medical applications.
Porous silicon (PS) which has different properties from the bulk material due to the quantum confinement effects is beside other physical properties (e.g., light emitting) bioactive or even bioresorbable. The aim of this paper is to optimise the experimental conditions for the fabrication of nanostructured Si particles and to find the best methods for attaching on its surface molecules of therapeutic interest. The selective porosification has been performed using (i) a dielectric/metallic masking layer micropatterned with corresponding etching windows; (ii) a controlled diffusion process leading to n-type islands into p-type Si substrate. The PS particles were detached from the Si substrate by switching the electrochemical etching conditions from porosification towards the electropolishing regime. Also, similar results were obtained by fabrication of PS multilayer structures subjected to an additional ultrasonation process. Different organic molecules with antitumoral effect, such as chondroitin sulphate (a sulphated glycosaminoglycan), lactoferrin (globular protein with antimicrobial activity) and N-butyldeoxynojirimycin (an imino sugar that inhibits the growth of the CT-2A brain tumour) were covalently attached on the PS particle surface using 3-aminopropyltriethoxysilane (APTS) molecule as linker. Furthermore, to complete the administration/therapy of drugs, for microparticle targeting and imaging, Fe3O4 nanoparticles were integrated in PS matrix by co-precipitation from a solution of iron salts (Fe3+/Fe2+) in alkaline medium. Microscopic and spectroscopic analyses have been used to characterize the Si microparticles. Tumoral cells were cultivated on the nanostructured PS particles and a significant decrease of the cells density was observed on all investigated samples comparatively with the blank substrate without antitumoral molecules.


Specificity of lymphocyte stimulation in vitro by microbial preparations: importance of antigen concentration.
Blood mononuclear cells were stimulated in vitro by 7 different microbial preparations, and thymidine incorporation was investigated in 7 groups of persons sensitized to the microorganisms and in 7 groups of controls. The sensitized persons were: 18 BCG-vaccinated, 13 with previous Mycoplasma pneumoniae pneumonia, 22 who had serum antibodies to Herpes simplex virus, 14 with previous typhoid fever, 13 with previous acute pyelonephritis caused by Eschrerichia coli, 6 with previous Haemophilus influenzae meningitis, and 15 tetanus-vaccinated persons. Employing microbial preparations corresponding to the type of sensitization, higher responses were obtained with PPD, Mycoplasma pneumoniae, Herpes simplex virus, Salmonella typhi and tetanus toxoid in sensitized than in controls, but the responses to E. coli and H. influenzae were similar. In each experiment a dose titration of the microbial preparation was carried out. The best separation between sensitized and non-sensitized persons was obtained at low concentrations, giving submaximal stimulation. It is concluded that lymphocyte responses to many microbial preparations are combined of antigen-specific components and of responses to cross-reacting or polyclonally activating moieties, and that the antigen-specific response is best investigated at low concentrations of these preparations.