C-reactive protein/abumin ratio is a useful biomarker for predicting the mucosal healing in the Crohn disease: A retrospective study.
Ileocolonoscopy is currently recognized as the gold standard for evaluating mucosal healing in patients with Crohn disease (CD). However, the ideal noninvasive marker to assess mucosal healing instead of invasive ileocolonoscopy is not available. This study aimed to determine the correlations between the mucosal healing and serological optimizing markers in CD.This retrospective study consecutively included 62 CD patients with 137 hospitalizations between March 2014 and March 2020. On the basis of the Simple Endoscopic Score for Crohn's disease (SES-CD), the CD patients were divided into mucosal healing group (SES-CD ≤ 2) and nonmucosal healing group (SES-CD > 2). We collected the results of ileocolonoscopy examination and inflammatory markers and then serological optimizing markers, including C-reactive protein/albumin ratio (CRP/ALB), platelet/albumin ratio (PLT/ALB), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) were calculated. The control group consisted of 50 healthy volunteers in the corresponding period.We found that CRP/ALB, PLT/ALB, NLR, and PLR were correlated with the mucosal healing of CD, and the correlation of CRP/ALB with the mucosal healing was the highest (r = -0.64). Receiver operating characteristic (ROC) analysis showed that the area under the curve (AUC) of CRP/ALB (0.87) was higher than NLR (0.69), PLR (0.72), and PLT/ALB (0.81). In the efficacy of assessing the mucosal healing in CD, the sensitivity of CRP/ALB, NLR, PLR, and PLT/ALB were 91.1%, 83.9%, 73.2%, and 73.2%, respectively, and the specificity was 76.5%, 46.9%, 64.2%, and 75.3%, respectively.CRP/ALB was the most appropriate marker to assess CD mucosal healing among the serological optimizing markers.


Papain kinetics in the presence of a water-miscible organic solvent.
The effects of various concentrations of a water-miscible organic solvent [a 7:3 (v/v) mixture of N, N dimethylformamide and dimethylsulfoxide] on the kinetics of papain have been investigated. The parameters k(cat) and K(m) for the amidase and esterase activity of papain using N-alpha-benzoyl-DL-arginine-p-nitroanilide (BAPNA) and N-alpha-benzoyl-L-arginine ethyl ester (BAEE) as substrates were determined. For both types of activity, k(cat) initially increased (up to about 15% solvent), and then decreased with increasing concentrations of organic solvent. In contrast, K(m) increased sharply with the organic solvent concentration. Active site titration at 0 and 50% solvent indicated no change in the amount of active enzyme. Fluorometric measurements of the emission spectrum of papain did not indicate any major conformational changes with increasing concentrations of organic solvent.


[Glycol ethers reproductive risks].
Glycol ethers (GE) are a family of solvents, the use of which has increased dramatically since the 60's, in domestic and occupational mainly water-based products, such as paintings, inks, varnishes, cleaning agents. There are two subgroups: E series and P series. EGME, among the E series, is the reference substance. This is a reprotoxic chemical causing infertility and genital apparatus atrophy on both sexes, embryofetal toxicity through maternal exposure (malformation, growth alterations and functional deficits). European Union has classified nine other GE as reprotoxic. P series, with the beta isomers exception, has no specific reprotoxicity. Epidemiological studies published from the 80's onwards, have confirmed animal data (malformation, oligoazoospermia, spontaneous abortion, hypofertility). The effects can be observed even after the end of exposure. Risk assessment studies tend to prove that this massive exposure during several decades could have had an important impact on reproductive human health. Even if this exposure has considerably decreased since the last few years, a ban of reprotoxic GE, as required by two official bodies (CSC, CSHPF), seems necessary, due to the high risk level. Classification should be completed for some GE, not classified now (EGBE). Health assessment of past exposure should be carried out. Physicians should look after a possible glycol ethers responsibility when facing this kind of reprotoxic effects.


Impact of a person-centred group intervention on life satisfaction and engagement in activities among persons aging in the context of migration‡.
Background: There is a growing need to support the health and wellbeing of older persons aging in the context of migration.Objectives: We evaluated whether a group-based health promotion program with person-centred approach, maintained or improved life satisfaction and engagement in activities of older immigrants in Sweden.Methods: A randomised controlled trial with post-intervention follow-ups at 6 months and 1 year was conducted with 131 older independently living persons aged ≥70 years from Finland and the Balkan Peninsula. Participants were randomly allocated to an intervention group (4 weeks of group intervention and a follow-up home visit) and a control group (no intervention). Outcome measures were life satisfaction and engagement in activities. Chi-square and odds ratios were calculated.Results: The odds ratios for maintenance or improvement of life satisfaction (for social contact and psychological health) were higher in the person-centred intervention group. More participants in the intervention group maintained or improved their general participation in activities compared with the control group. However, no significant between-group differences were found.Conclusion: Person-centred interventions can support older person's capability to maintain their health in daily life when aging in migration. Further research is needed with a larger sample and longer intervention period to determine the effectiveness of the intervention.


[Clinical features of preeclampsia-eclampsia patients with reversible posterior leukoencephalopathy syndrome].
To investigate the clinical features and specific characteristics of magnetic resonance image (MRI) in preeclampsia-eclampsia patients with reversible posterior leukoencephalopathy syndrome (RPLS). The investigators analyzed the combined clinical, laboratory and neuroradiographic features of 20 preeclampsia-eclampsia patients with RPLS and 15 preeclampsia-eclampsia controls with normal MRI findings. Patients with RPLS had more tendency to have headache, seizure, visual disturbance, confusion and altered mental status than controls. Neuroimaging showed diffuse edema predominantly in posterior cerebral white matter bilaterally. Clinical features and neuroradiological alterations disappeared after appropriate treatments were started. Twenty RPLS patients had a significantly higher level of uric acid (442 +/- 77 mmol/L) than those without RPLS (350 +/- 88 mmol/L) (P < 0.05). However no difference was observed for other indices. Preeclampsia-eclampsia patients with RPLS have typical clinical and imaging findings, and the syndrome is reversible with appropriate treatment. Perhaps endothelial damage is related to the pathogenesis of RPLS. Monitoring the level of uric acid in patients with preeclampsia-eclampsia is of vital significance to discover RPLS in an early stage.


Effect of early corticosteroid therapy on development of Henoch-Schönlein nephritis.
Henoch-Schönlein purpura (HSP) is a systemic, small vessel vasculitis, which is very common among pediatric population. Findings of previous reports addressing the preventive effect of corticosteroid treatment in HSP nephritis have been inconsistent. The aim of this study was to determine whether corticosteroid therapy was effective in preventing Henoch-Schönlein nephritis. The medical records of 216 children with HSP, seen in 2 tertiary care pediatric nephrology centers, were reviewed retrospectively. The effect of corticosteroid therapy on preventing nephritis was assessed in 157 patients who had no evidence of nephritis at the initial urinalysis. The treatment group (n=61) had received oral corticosteroids for gastrointestinal symptoms and/or arthritis. The dosage of prednisone was 1 mg/kg per day for 1-2 weeks, with weaning over a week. We compared the rate of renal involvement during follow-up between the groups who were treated with corticosteroids and not. Nephritis developed in 17 of the 61 (27.8%) corticosteroid-treated patients and 18 of the 96 (18.7%) untreated patients during follow-up. There was no evidence that corticosteroids reduced the risk of renal involvement in HSP, and these results do not support the use of corticosteroids in early HSP to prevent renal injury.


Comparison of three types of treatment modalities on the outcome of fingertip injuries.
In this retrospective study, we analyzed the outcomes of different types of treatment of fingertip injuries and compared them after a mean follow-up of 4.5 years. A total of 53 patients (59 injuries) were included in this study. The fingertip injuries were classified according to Allen classification. The patients were categorized into three groups based on the treatment: reconstructive group, bone-shortening group, and conservative group. As objective assessments, strength, sensibility, and goniometry were measured; as subjective assessments, cold intolerance, nail deformation, and aesthetics were measured. The mean reduction in strength, the Semmes-Weinstein monofilament test, and the reduction in mobility for the injured fingers compared with those of the uninjured finger were not significantly different between the groups. Cold intolerance was reported in 50 (84.7%) of the 59 fingers, and in almost 90% of all the cases, there was some kind of nail distortion. For the cold intolerance and nail distortions, there was no difference between the groups. The aesthetic outcomes judged by patients and surgeon were comparable. In conclusion, the outcome of treatment of Allen II, III, and IV fingertip injuries was irrespective of the treatment chosen. In an era where the enormous variety of surgical options suggests that treatment with a flap is the best, this outcome is at least surprising. Therapeutic study, level IV.


Erythromycin, motilin, and the esophagus.
Motilin induces phase III activity of the gastroesophageal tract. Erythromycin has a motilin-like effect on the stomach, but possible esophageal effects have not been evaluated and are the focus of our investigation. Esophageal manometry was performed in 11 healthy volunteers before and after intravenous infusion of 500 mg erythromycin. Values are expressed as means +/- SEM. Lower esophageal sphincter (LES) pressure increased from 21.1 +/- 2.6 mm Hg at baseline to 37.5 +/- 3.8 mm Hg after erythromycin infusion (p < 0.0001). Erythromycin did not affect LES length, esophageal body contraction amplitude, duration or velocity, or the upper esophageal sphincter. Serum motilin levels decreased from 96.4 +/- 10.9 pmol/L to 81.8 +/- 10.9 pmol/L (p < 0.01) after erythromycin administration. Erythromycin profoundly stimulates the normal human LES. This is a direct motilin agonist-like effect and is not mediated by release of endogenous motilin. Erythromycin has no important effect on the esophageal body or the upper esophageal sphincter.


Variation of sensitivity, specificity, likelihood ratios and predictive values with disease prevalence.
The sensitivity, specificity and likelihood ratios of binary diagnostic tests are often thought of as being independent of disease prevalence. Empirical studies, however, have frequently revealed substantial variation of these measures for the same diagnostic test in different populations. One reason for this discrepancy is related to the fact that only few diagnostic tests are inherently dichotomous. The majority of tests are based on categorization of individuals according to one or several underlying continuous traits. For these tests, the magnitude of diagnostic misclassification depends not only on the magnitude of the measurement or perception error of the underlying trait(s), but also on the distribution of the underlying trait(s) in the population relative to the diagnostic cutpoint. Since this distribution also determines prevalence of the disease in the population, diagnostic misclassification and disease prevalence are related for this type of test. We assess the variation of various measures of validity of diagnostic tests with disease prevalence for simple models of the distribution of the underlying trait(s) and the measurement or perception error. We illustrate that variation with disease prevalence is typically strong for sensitivity and specificity, and even more so for the likelihood ratios. Although positive and negative predictive values also strongly vary with disease prevalence, this variation is usually less pronounced than one would expect if sensitivity and specificity were independent of disease prevalence.


Vocational Rehabilitation and Employment Program--periods of eligibility. Final rule.
This document adopts without change the proposed rule published in the Federal Register on March 9, 2009, amending regulations of the Department of Veterans Affairs (VA) concerning periods of eligibility applicable to VA's provision of Vocational Rehabilitation and Employment benefits and services. The amendments clarify program requirements, interpret and incorporate new statutory requirements, and make clarifying non-substantive changes.


[Invasive and non-invasive methods for the diagnosis of tachycardia].
Surface ECG permits, in most cases, to determine the ventricular or supraventricular origin of a tachycardia with wide complexes, to individualize VTs with aspects of Left Buble Branch and left axis, to visualize epsilon waves in some chronic VTs. The late potentials detected by the sum-mean method seem to be well correlated with the occurrence of ventricular tachycardia, especially after myocardial infarction. The area of origin of a VT may be determined quite precisely by cartography and topographic stimulation. The predictive value of the provocation methods (stress test, transesophageal stimulation, endocardiac stimulation) is discussed. Some arrhythmias may be discovered on ultrasonic cardiography and the exact mechanism of some reciprocal permanent junctional tachycardias is well demonstrated with endocardiac stimulation and fulguration. Nuclear magnetic resonance offers a new possibility of etiological diagnosis in ventricular tachycardias with left delay.


Study on in situ calibration for neutron flux monitor in the Large Helical Device based on Monte Carlo calculations.
Neutron monitoring is important to manage safety of fusion experiment facilities because neutrons are generated in fusion reactions. Monte Carlo simulations play an important role in evaluating the influence of neutron scattering from various structures and correcting differences between deuterium plasma experiments and in situ calibration experiments. We evaluated these influences based on differences between the both experiments at Large Helical Device using Monte Carlo simulation code MCNP5. A difference between the both experiments in absolute detection efficiency of the fission chamber between O-ports is estimated to be the biggest of all monitors. We additionally evaluated correction coefficients for some neutron monitors.


Morphological changes after duct ligation of rabbit pancreas.
The morphological changes in rabbit pancreases after duct ligation were studied. These changes do not occur synchronically within the whole pancreas. The most advanced are those in the head portion; in the tail, their development is delayed. Pancreas duct ligation results in the pancreas edema, a gradual disappearance of zymogenous cells, replacement of acini by small ducts, an occasional differentiation of new zymogenous cells that quickly extinct again, and with the occurrence of amorphous or even fibrillary masses in the cytoplasm of duct cells to their further reduction. These changes are accompanied by the formation of loose connective tissue which gradually fibrotizes. The islets of Langerhans also undergo changes. In the tubules, a differentiation appears of their cells into endocrine elements. The existing islets get destroyed by both the fibrotic tissue and the formation of cavities in large islets with a consequent break-up of those islets. Both these destructive processes, in connection with the new formation, result in the appearance of small islets on the surface of which there is a capillary network. The cells of those islets are not of a fetal character.


Globule-size distribution in injectable 20% lipid emulsions: Compliance with USP requirements.
The compliance of injectable 20% lipid emulsions with the globule-size limits in chapter 729 of the U.S. Pharmacopeia (USP) was examined. As established in chapter 729, dynamic light scattering was applied to determine mean droplet diameter (MDD), with an upper limit of 500 nm. Light obscuration was used to determine the size of fat globules found in the large-diameter tail, expressed as the volume-weighted percent fat exceeding 5 microm (PFAT(5)), with an upper limit of 0.05%. Compliance of seven different emulsions, six of which were stored in plastic bags, with USP limits was assessed. To avoid reaching coincidence limits during the application of method II from overly concentrated emulsion samples, a variable dilution scheme was used to optimize the globule-size measurements for each emulsion. One-way analysis of variance of globule-size distribution (GSD) data was conducted if any results of method I or II exceeded the respective upper limits. Most injectable lipid emulsions complied with limits established by USP chapter 729, with the exception of those of one manufacturer, which failed limits as proposed for to meet the PFAT(5) three of the emulsions tested. In contrast, all others studied (one packaged in glass and three packaged in plastic) met both criteria. Among seven injectable lipid emulsions tested for GSD, all met USP chapter 729 MDD requirements and three, all from the same manufacturer and packaged in plastic, did not meet PFAT(5) requirements.


Antagonistic activity of auxin and cytokinin in shoot and root organs.
The hormones auxin and cytokinin are essential for plant growth and development. Because of the central importance of root and shoot apical meristems in plant growth, auxin/cytokinin interactions have been predominantly analyzed in relation to apical meristem formation and function. In contrast, the auxin/cytokinin interactions during organ growth have remained largely unexplored. Here, we show that a specific interaction between auxin and cytokinin operates in both the root and the shoot where it serves as an additional determinant of plant development. We found that auxin at low concentrations limits the action of cytokinin. An increase in cytokinin level counteracts this inhibitory effect and leads to an inhibition of auxin signaling. At higher concentrations of both hormones, these antagonistic interactions between cytokinin and auxin are absent. Thus, our results reveal a bidirectional and asymmetrical interaction of auxin and cytokinin beyond the bounds of apical meristems. The relation is bidirectional in that both hormones exert inhibitory effects on each other's signaling mechanisms. However, this relation is also asymmetrical because under controlled growth conditions, auxin present in nontreated plants suppresses cytokinin signaling, whereas the reverse is not the case.


Direct Time-Domain View of Auger Recombination in a Semiconductor.
The radiationless recombination of electron-hole pairs in semiconductors is detrimental to optoelectronic technologies. A prominent mechanism is Auger recombination, in which nonradiative recombination occurs efficiently by transferring the released energy-momentum to a third charge carrier. Here we use femtosecond photoemission to directly detect Auger electrons as they scatter into energy and momentum spaces from Auger recombination in a model semiconductor, GaSb. The Auger rate is modulated by a coherent phonon mode at 2 THz, confirming phonon participation in momentum conservation. The commonly assumed Auger rate constant is found not to be a constant, but rather decreases by 4 orders of magnitude as hot electrons cool down by ∼90 meV. These findings provide quantitative guidance in understanding Auger recombination and in designing materials for efficient optoelectronics.


Dialyzer membranes: effect of surface area and chemical modification of cellulose on complement and platelet activation.
Using an ex vivo model, the effects of membrane composition and surface area on both the complement system (as reflected by plasma C3a levels) and platelets [as indicated by plasma concentrations of thromboxane B2 (TXB2) and platelet factor 4 (PF4)] were studied. In this model, polyacrylonitrile (PAN) was associated with less complement activation than cuprammonium cellulose (CC). A new "modified cellulose" (MC) membrane, in which a small number of the free hydroxyl groups on cellulose are substituted with a tertiary amino compound, was also associated with a low degree of complement activation, similar to that with PAN. However, the extent of hydroxyl group substitution in four MC membrane subtypes did not correlate with the reduction in complement activation. In studies using CC, the amount of generated C3a correlated with the membrane surface area, although the relationship was curvilinear. Plasma concentrations at the "dialyzer" outlet of TXB2 and PF4 were similar with CC, PAN, and MC. In studies with the MC subtypes, increasing the extent of hydroxyl group substitution paradoxically increased, albeit slightly, the amount of TXB2 generation. In studies with CC, a linear relationship between membrane surface area and TXB2 generation was found. The results suggest a dissociation between platelet and complement effects among different dialyzer membranes, and underline the importance of membrane surface area.


[Diagnosis of spontaneous ascites infection in patients with cirrhosis: reagent strips].
To evaluate the sensitivity, specificity, and predictive values of dipstick testing (DT) for detecting spontaneous bacterial peritonitis (SBP), defined by an ascites neutrophil polymorphonuclear cell count > or = 250/mm3, in patients with cirrhosis. The study includes all patients with cirrhosis and ascites admitted to our general hospital on the southern outskirts of the Paris metropolitan area (France) from June 2003 to May 2004 (n = 47:27 men and 20 women). Diagnostic abdominal paracentesis was performed on admission, and a Multistix SG (Bayer Pharma) reagent strip was immersed in one ascitic sample from each patient. Readings after 120 s were either negative (DT-) or positive (DT+, with 4 levels of positivity: trace, +, ++, or +++). In case of cytologically-proven SBP, patients were treated with cefotaxime, and subsequent paracentesis with DT and cytologic testing took place every 48 hours, until recovery. Six of the 47 patients had proven SBP, all with clinical signs of SBP (fever and/or abdominal pain); five of these patients were DT+ and one was DT-. In the five patients initially DT+, the DT became negative at the same time as the cytologic criteria for SBP disappeared. Forty-one patients did not meet the cytologic criteria for SBP: 34 were DT- and 7 were DT+ (traces: 4, ++: 2, +++:1); two of these had clinical signs suggestive of SBP. Although the sensitivity (83%), specificity (83%) and negative predictive value (97%) of DTwere satisfactory, its positive predictive value (42%) was low. Dipstick testing of ascitic fluid is easy to perform and inexpensive and may be recommended for diagnosis and follow-up of SBP, especially in emergency settings.


Entamoeba polecki: morphology, immunology, antigen study and clinic of the first infections in Czechoslovakia.
Entamoeba polecki Prowazek, 1912 was recorded for the first time in Czechoslovakia in two students from Kampuchea. Uninucleated cysts of diameter 14.2-15.7 micron with nuclei diameter 3.2-4.2 micron were found-repeatedly in stool samples taken from them. The nucleus accounted in average for 24.3% of the cyst diameter. The isolation and two following subinoculations on Dobell-Leidlaw medium were achieved, more abundant growth was recorded on medium with pig serum. Sera of both students were positive in serological tests using the E. histolytica antigen. No serious clinical symptoms were observed, both patients were cured successfully by metronidazole and ornidazole. Electroimmunotransfer blots were used to characterize E. polecki as a separate species. The antigenic structure of polyxenically grown E. polecki was compared with the antigenic structure of E. histolytica (axenically grown HK-9 strain and 3 polyxenically grown strains). Different blot patterns of both species were obtained, but common fractions of 30-40 kD probably responsible for serological cross-reactions were found.


Pemetrexed exerts anticancer effects by inducing G0/G1-phase cell cycle arrest and activating the NOXA/Mcl-1 axis in human esophageal squamous cell carcinoma cells.
Esophageal squamous cell carcinoma (ESCC) is a dominant histological subtype of esophageal cancer with notably high incidence and mortality rates. Pemetrexed is a clinical antifolate therapeutic agent with anticancer properties. The present study aimed to understand whether pemetrexed is able to exert anticancer effects on ESCC cells, and to determine the underlying molecular mechanism. ESCC cells were treated with pemetrexed and cell survival was assessed with MTT assays. The cell cycle and apoptosis were evaluated using flow cytometry analysis, and proteins were detected using western blotting. It was demonstrated that pemetrexed inhibited cell survival and induced G0/G1 cell cycle arrest and apoptosis in human ESCC cells. Furthermore, the results demonstrated that the phorbol-12-myristate-13-acetate-induced protein 1/induced myeloid leukemia cell differentiation protein Mcl-1 axis is involved in intrinsic apoptosis induced by pemetrexed. The protein expression of endoplasmic reticulum stress markers inositol-requiring enzyme 1α, binding immunoglobulin protein and CCAAT-enhancer-binding protein homologous protein were upregulated following treatment with pemetrexed. These results suggest that pemetrexed may induce an endoplasmic reticulum stress response while activating intrinsic apoptosis. The present study provided important mechanistic insights into potential cancer treatments involving pemetrexed and enhanced the understanding of human ESCC.


Immune cell recruitment and cell-based system for cancer therapy.
Immune cells, such as cytotoxic T lymphocytes, natural killer cells, B cells, and dendritic cells, have a central role in cancer immunotherapy. Conventional studies of cancer immunotherapy have focused mainly on the search for an efficient means to prime/activate tumor-associated antigen-specific immunity. A systematic understanding of the molecular basis of the trafficking and biodistribution of immune cells, however, is important for the development of more efficacious cancer immunotherapies. It is well established that the basis and premise of immunotherapy is the accumulation of effective immune cells in tumor tissues. Therefore, it is crucial to control the distribution of immune cells to optimize cancer immunotherapy. Recent characterization of various chemokines and chemokine receptors in the immune system has increased our knowledge of the regulatory mechanisms of the immune response and tolerance based on immune cell localization. Here, we review the immune cell recruitment and cell-based systems that can potentially control the systemic pharmacokinetics of immune cells and, in particular, focus on cell migrating molecules, i.e., chemokines, and their receptors, and their use in cancer immunotherapy.


Understanding of Future Prescribers About Antimicrobial Resistance and Their Preparedness Towards Antimicrobial Stewardship Activities in Pakistan: Findings and Implications.
Background: Insufficient antimicrobial-related training for physicians during their undergraduate education could have a negative impact on their prescribing. Unlike previous studies, this study not only explored the understanding and perception of Pakistani medical students about antibiotics and resistance, but also their preparedness towards antimicrobial stewardship programs. Methods: An online cross-sectional study was undertaken with final-year medical students using a validated questionnaire from January 2021 to May 2021. Descriptive and inference statistics were applied for data analysis. Results: Of 411 students, only 6.3% had undergone antimicrobial resistance (AMR) training. 16.1% of students believed that antibiotics are effective for viral ailments. More than half of the students agreed that AMR is a major healthcare problem in Pakistan (65.9%). Most students viewed poor infection control practices (66.9%), the use of too many broad-spectrum antibiotics (68.4%) for a longer duration (62.8%) with inadequate doses (67.9%) as the causes of AMR. The student's preparation was insufficient in interpreting microbiological and pathological results (26.3%), selecting the correct antibiotics (22.1%), and awareness of the antibiotic spectrum (20.9%). The median preparedness score showed significant differences with sex (p = 0.049), age (p < 0.001), institute type (p = 0.014), and family income (p = 0.006). Conclusion: Pakistani medical students showed adequate understanding of antibiotics, but lacked preparedness for several components of ASPs, including interpretation of microbiological results and spectrum of antibiotics. More steps need to be taken to prepare medical students for AMR and stewardship initiatives adequately.


Innate immunity changes in soccer players after whole-body cryotherapy.
Whole-body cryotherapy (WBC) consists of short exposure (up to 2-3 min) to dry air at cryogenic temperatures (up to -190 °C) and has recently been applied for muscle recovery after injury to reduce the inflammation process. We aimed to determine the impact of cryotherapy on immunological, hormonal, and metabolic responses in non-professional soccer players (NPSPs). Nine male NPSPs (age: 20 ± 2 years) who trained regularly over 5 consecutive days, immediately before and after each training session, were subjected to WBC treatment (WBC-t). Blood samples were collected for the evaluation of fifty analytes including hematologic parameters, serum chemistry, and hormone profiles. Monocytes phenotyping (Mo) was performed and plasmatic markers, usually increased during inflammation [CCL2, IL-18, free mitochondrial (mt)DNA] or with anti-inflammatory effects (IL2RA, IL1RN), were quantified. After WBC-t, we observed reduced levels of ferritin, mean corpuscular hemoglobin, mean platelet volume, testosterone, and estradiol, which however remain within the normal ranges. The percentage of the total, intermediates and non-classical Mo increased, while classical Mo decreased. CXCR4 expression decreased in each Mo subset. Plasma IL18 and IL2RA levels decreased, while IL1RN only exhibited a tendency to decrease and CCL2 showed a tendency to increase. Circulating mtDNA levels were not altered following WBC-t. The differences observed in monocyte subsets after WBC-t may be attributable to their redistribution into the surrounding tissue. Moreover, the decrease of CXCR4 in Mo subpopulations could be coherent with their differentiation process. Thus, WBC through yet unknown mechanisms could promote their differentiation having a role in tissue repair.


Photexcitation of aqueous ruthenium(II)-tris-(2,2'-bipyridine) with high-intensity femtosecond laser pulses.
We report a femtosecond pump-probe study on the photochemistry of concentrated aqueous solutions of [RuII(bpy)3]2+, as a function of pump power (up to 2 TW/cm2) at 400 nm excitation. The transient absorption spectra in the 345-660 nm range up to 1 ns time delay enable the observation of the following photoproducts: the triplet 3MLCT (metal-to-ligand-charge-transfer) excited state, the reduced form [RuII(bpy)3]+, the oxidized species [RuIII(bpy)3]3+, and the solvated electron e(aq). The 3MLCT state is formed within the excitation pulse and undergoes vibrational relaxation in 3-5 ps, as evidenced by the shift of the ligand-centered (LC) absorption band below 400 nm. Even at the highest pump powers, the majority of e(aq) originates from multiphoton ionization of [RuII(bpy)3]2+ and not from the solvent, generating [RuIII(bpy)3]3+ as a byproduct. At 10 ps time delay, the total concentration of the three product species is balanced by the depleted concentration of [RuII(bpy)3]2+, even at the highest fluences used, indicating that no further reaction products significantly contribute to the overall photochemistry. On the 100 ps time scale, most probably diffusion-controlled reduction of ground-state [RuII(bpy)3]2+ by solvated electrons occurs, next to recombination between e(aq) and [RuIII(bpy)3]3+.


The Influence of Spirulina platensis Filtrates on Caco-2 Proliferative Activity and Expression of Apoptosis-Related microRNAs and mRNA.
Spirulina platensis (SP) is a blue-green microalga that has recently raised attention not only as a nutritional component, but also as a source of bioactivities that have therapeutic effects and may find application in medicine, including cancer treatment. In the present study we determined the cytotoxic effect of S. platensis filtrates (SPF) on human colon cancer cell line Caco-2. Three concentrations of SPF were tested-1.25%, 2.5%, and 5% (v/v). We have found that the highest concentration of SPF exerts the strongest anti-proliferative and pro-apoptotic effect on Caco-2 cultures. The SPF negatively affected the morphology of Caco-2 causing colony shrinking and significant inhibition of metabolic and proliferative activity of cells. The wound-healing assay showed that the SPF impaired migratory capabilities of Caco-2. This observation was consistent with lowered mRNA levels for metalloproteinases. Furthermore, SPF decreased the transcript level of pro-survival genes (cyclin D1, surviving, and c-Myc) and reduced the autocrine secretion of Wnt-10b. The cytotoxic effect of SPF involved the modulation of the Bax and Bcl-2 ratio and a decrease of mitochondrial activity, and was related with increased levels of intracellular reactive oxygen species (ROS) and nitric oxide (NO). Moreover, the SPF also caused an increased number of cells in the apoptotic sub-G0 phase and up-regulated expression of mir-145, simultaneously decreasing expression of mir-17 and 146. Obtained results indicate that SPF can be considered as an agent with anti-cancer properties that may be used for colon cancer prevention and treatment.


The relationship between STD locus of control and STD acquisition among adolescent girls.
This longitudinal study examined adolescent girls' perception of control over sexually transmitted disease (STD) acquisition. Participants were asked questions regarding their perception of their STD locus of control (internal control; control by parents, partners, peers, and health care providers; and chance) at two waves of data collection. Of the 116 participants (mean age = 17 years), 82% were African-American and 18% were Caucasian. Responses to the measure of locus of control were significantly correlated across a 6-month interval. The responses regarding internal control, control by partner, and chance were not related to the acquisition of an STD in the next 6 months. Further, they were not influenced by an STD in the preceding 6 months. These results indicate that responses to a locus of control measure were stable over a 6-month period, and internal, partner, and chance locus of control perceptions seem to be neither determined by STD experience nor directly related to future STD acquisition. However, understanding an individual's locus of control may be helpful in providing appropriate counseling. Future research could examine how adolescent girls form their perceptions of control over STD acquisition.


An X-chromosome scan reveals a locus for fat distribution in chromosome region Xp21-22.
Several groups have completed autosomal genome scans for human obesity, but only two have examined the X chromosome. A French group reported linkage of BMI to Xp and Xq markers, and a Finnish group reported linkage of BMI to Xq. We scanned the X chromosome in two cohorts, 190 European-American families (940 members) and 43 African-American families (208 members). We examined five correlated obesity phenotypes, BMI, body fat percentage, hip and waist circumferences, and plasma leptin concentration. We also examined leptin resistance (leptin/BMI) and fat patterning (waist-to-hip ratio [WHR]). Variables were adjusted for age within generation, race, and sex. We genotyped 20 markers with average spacing of 10 cM and no interval >22 cM and conducted nonparametric analyses. Suggestive linkage was found for WHR only. Linkage was supported in both family sets, and support was especially strong for females. Z scores for analyses of female phenotypes were 2.69, 1.73, and 2.37 (P = 0.0036, 0.0418, and 0.0089) for African-Americans, European-Americans, and the combined sample, respectively. The peaks were 51-73 cM from the p terminus, 14-34 cM distal of the French report in Xp22. Our results suggest that a quantitative trait locus influencing fat distribution in women may lie in chromosome region Xp21-22; however, the linked interval is large and differs substantially from that of the French and Finnish groups. Given the positive but divergent results, it would be worthwhile for others to examine the X chromosome.


VOLUMETRIC ASSESSMENT OF THE RESPONSIVENESS OF PIGMENT EPITHELIAL DETACHMENTS IN NEOVASCULAR AGE-RELATED MACULAR DEGENERATION TO INTRAVITREAL BEVACIZUMAB.
To determine baseline factors that can predict the response of pigment epithelial detachments (PEDs) in neovascular age-related macular degeneration to treatment with intravitreal bevacizumab (IVB). Patients with newly diagnosed neovascular age-related macular degeneration and PED who were treated exclusively with IVB were included. Response to treatment was defined by change in PED volume (determined using spectral-domain optical coherence tomography). PEDs were classified as either predominantly serous or fibrovascular. Multivariable regression and receiver operating characteristic analyses were performed. A total of 48 eyes were identified (mean follow-up time 73 weeks). Overall, the response to the first IVB treatment was predictive of the response to treatment at the final visit (P = 0.015). Serous PEDs had a greater decrease in volume at the final visit (P = 0.008). With respect to both PED types, a decrease in PED volume of 21% after the first IVB treatment was predictive of an overall decrease in volume of 30% at the final visit (sensitivity 83%, specificity 76%). In neovascular age-related macular degeneration, serous PEDs respond more favorably to IVB than fibrovascular PEDs. Overall, for both types of PED, the response to the first treatment is predictive of the final response to treatment. Taken together, the results would suggest that if there is less than 21% reduction in PED volume after the first IVB treatment, and/or the PED is predominantly fibrovascular, then switching to another antivascular endothelial growth factor agent should be considered.


Regulation of steroidogenesis in subclones of the MA-10 mouse Leydig tumor cell line.
We have previously reported the isolation of a subclone of the MA-10 mouse Leydig tumor cell line (MA-10 LP) which secretes less than 10% of the steroid synthesized by the parent, accumulates comparable amounts of cAMP and has equivalent cholesterol side-chain cleavage activity as the parent population (Kilgore and Stocco (1989) Endocrinology 124, 1210-1216). In the present study we show that addition of exogenous sterol carrier protein 2 (SCP2) to isolated mitochondria was not able to overcome the deficient steroid response of MA-10 LP. We have also demonstrated that human chorionic gonadotropin (hCG)-stimulated cellular events which activate steroid production by subsequently isolated mitochondria require ongoing protein synthesis, release of intracellular calcium and are mediated through the calcium-calmodulin complex. Additionally, mitochondrial sonicates from hCG-stimulated parent cells were able to stimulate steroid production by intact mitochondria isolated from unstimulated parent cells, whereas sonicates from similarly treated MA-10 LP had no effect on steroid production in these mitochondria. Together these data suggest that hCG induces changes in the mitochondria of the parent stock which are not induced to the same extent in the mitochondria of MA-10 LP.


Sterol 27-hydroxylase- and apoAI/phospholipid-mediated efflux of cholesterol from cholesterol-laden macrophages: evidence for an inverse relation between the two mechanisms.
Cholesterol-laden, human monocyte-derived macrophages were found to contain 27-hydroxycholesterol in proportion to their content of cholesterol ester. In accordance with previous work with human lung alveolar macrophages, there was a significant efflux of 27-hydroxycholesterol and 3beta-hydroxy-5-cholestenoic acid from the cultured cells. The efflux of 27-hydroxycholesterol was proportional to the cellular content of this steroid. Incubation of cholesterol-laden macrophages with reconstituted discoidal complexes made from apolipoprotein A-I and phospholipids resulted in a decrease in total cellular cholesterol, an increase in the efflux of free cholesterol, and a concomitant decrease in the total production and efflux of 27-oxygenated steroids, in particular, 3beta-hydroxy-5-cholestenoic acid. Reconstituted discoidal complexes with the Milano variant of apolipoprotein A-I gave virtually identical results, whereas high density lipoprotein was less efficient. These results suggest that cultured cholesterol-laden cells can export some of their excess cholesterol in the form of 27-hydroxycholesterol, 3beta-hydroxy-5-cholestenoic acid, and free cholesterol. In the presence of exogenous cholesterol acceptors, export of free cholesterol becomes more effective, resulting in less cholesterol exported via the 27-hydroxylase pathway. The balance between the two mechanisms for removal of cholesterol from macrophages may be of importance for formation of foam cells and development of atherosclerosis.


Comparison of genetic changes in frozen biopsies and microdissected archival material from the same colorectal liver metastases.
Microdissection of tissue sections from formalin-fixed, paraffin-embedded tumor material allows separation of microscopic sites within a sample. DNA can easily be extracted, and polymerase chain reaction (PCR) technology makes it possible to perform different molecular biologic analyses on small cell populations. The presence of normal cells or tumor heterogeneity may cause false negatives in allelic imbalance (AI) studies. Microdissected well-defined cell populations from a tumor section are assumed to increase the sensitivity of AI analyses. The present study has evaluated this in colorectal liver metastases by comparing genotypes in frozen biopsies with genotypes in microdissected archival samples from the same patients. Constitutional genotypes were obtained from corresponding peripheral blood leukocytes as well as normal liver tissue. Archival samples (n = 43) from 16 patients were analyzed after microdissection with 2-5 of 10 selected microsatellite markers. Frozen biopsies from one metastasis of each patient had previously been investigated at numerous microsatellite loci. From those results we selected, for the comparable analysis of archival samples, 41 tumor genotypes at 10 loci representing 11 heterozygotes, 13 AI, 7 losses of heterozygosity (LOHs), 8 homozygotes, and 2 microsatellite unstable cases. The microdissected samples revealed AI or a complete loss of one allele (LOH) in 5 of 11 (45%) genotypes that were previously evaluated as unchanged (retained heterozygosity) in the frozen biopsies, and LOH in 8 of 13 (62%) genotypes at loci known to exhibit AI in the frozen biopsies. Microsatellite instability, LOH, and homozygosity found in the frozen samples were all confirmed by analyses of the archival material. Intertumoral genetic heterogeneity was found in samples from two patients. The same allelic intensities were seen in DNA from tumor-close liver tissue as in blood DNA from the same patient except in one sample. The present study shows a 54% increase in sensitivity of genetic alterations if pure tumor cell components are used (five "new" AIs and LOHs and eight "new" LOHs among previously scored heterozygotes [n = 11] and AI [n = 13], respectively). In total, a 93% success rate (108/115 analyses) was obtained using standard PCR conditions for the 10 selected markers. The fact that standard PCR conditions and 5-micron tumor sections are used shows how easy these analyses are to perform, and that only minor amounts of valuable archival material is used.


Mixed News about the Bad News Game.
Basol et al. (2020) tested the "the Bad News Game" (BNG), an app designed to improve ability to spot false claims on social media. Participants rated simulated Tweets, then played either the BNG or an unrelated game, then re-rated the Tweets. Playing the BNG lowered rated belief in false Tweets. Here, four teams of undergraduate psychology students each attempted an extended replication of Basol et al., using updated versions of the original Bad News game. The most important extension was that the replications included a larger number of true Tweets than the original study and planned analyses of responses to true Tweets. The four replications were loosely coordinated, with each team independently working out how to implement the agreed plan. Despite many departures from the Basol et al. method, all four teams replicated their key finding: Playing the BNG reduced belief in false Tweets. But playing the BNG also reduced belief in true Tweets to the same or almost the same extent. Exploratory signal detection theory analyses indicated that the BNG increased response bias but did not improve discrimination. This converges with findings reported by Modirrousta-Galian and Higham (2023).


Adaptive neural control for a class of nonlinear time-varying delay systems with unknown hysteresis.
This paper investigates the fusion of unknown direction hysteresis model with adaptive neural control techniques in face of time-delayed continuous time nonlinear systems without strict-feedback form. Compared with previous works on the hysteresis phenomenon, the direction of the modified Bouc-Wen hysteresis model investigated in the literature is unknown. To reduce the computation burden in adaptation mechanism, an optimized adaptation method is successfully applied to the control design. Based on the Lyapunov-Krasovskii method, two neural-network-based adaptive control algorithms are constructed to guarantee that all the system states and adaptive parameters remain bounded, and the tracking error converges to an adjustable neighborhood of the origin. In final, some numerical examples are provided to validate the effectiveness of the proposed control methods.


Women's barriers for contacting general practice when experiencing gynecological cancer symptoms: a population-based study.
A prerequisite for general practitioners (GPs) being able to refer patients with gynecological cancer alarm symptoms for further investigations is that individuals present the symptoms to the GP. Not all symptoms are presented to the GP, and knowledge of barriers for healthcare-seeking is sparse. The aim of this study was to analyze associations between age, socioeconomic status, and common barriers ("being too embarrassed", "being too busy", "worried about wasting the doctors time" and "worried what the GP might find") towards GP contact with gynecological alarm symptoms. Nationwide population-based study in Denmark based on a random sample of 51 090 women aged 20 years or older. A web-based questionnaire regarding experience of four predefined alarm symptoms of gynecological cancer, decisions about contact to GPs, and barriers towards GP contact was distributed. Information about socioeconomic status was collected from Statistics Denmark. A total of 26 466 women (54.5%) completed the questionnaire. The proportion of women with no contact to the GP varied between 64.6% and 78.1% for postmenopausal bleeding and pain during intercourse, respectively. Between 32.3% (bleeding during intercourse) and 45.3% (postmenopausal bleeding) of the women reported no barriers for GP contact. The proportions of reported barriers ranged from 7.5% for being too embarrassed (pelvic pain) to 26.8% for being too busy (bleeding during intercourse). Women aged 40-59 years had lower odds of reporting "being too embarrassed" and "worried about wasting the GP´s time", while women aged 60 + years of age had lower odds of reporting "being too busy" compared to the youngest age group. Women in the highest income groups had lower odds of reporting "being too embarrassed" and "wasting the GP´s time" compared to those with a low income, while those with high educational level had lower odds of reporting "being too embarrassed" and "worried what the GP might find" compared to those with low educational level. More than half of the respondents with no contact to the GP, reported one or more barriers towards GP contact. Lower age and socioeconomic status were significantly associated with higher odds of reporting barriers. As this may explain the differences in healthcare seeking behavior, healthcare planners, policy makers and clinicians should be aware of these findings.


Diameter comparison of saphenous vein bypasses for popliteal aneurysm versus peripheral arterial occlusive disease in matched subjects.
Previous research has suggested that arterial aneurysm might result from a systemic tendency to dilatation. This systemic effect would involve both arterial and venous dilatation. The authors investigated whether venous grafts implanted to bypass popliteal artery aneurysms (PAA) had larger diameters than those implanted to treat peripheral arterial occlusive disease (PAOD). They compared representative diameters of 20 vein grafts implanted for PAA with matched bypass grafts implanted for PAOD. Graft diameters were obtained by means of CVI-Q M-mode ultrasound imaging. Each PAA patient/graft was matched to an equivalent PAOD patient/graft based on the patient's gender and age and the vein graft type and distal anastomosis. Secondarily, graft proximal anastomosis was matched in 60% (12/20) of the cases. Age was matched if the difference was < or = 4 years. Average age at the time of surgery was 68 +/-12 years for PAA and 68 +/-13 for PAOD groups. There were 11 reversed greater saphenous vein (GSV), 2 nonreversed GSV, and 7 in situ GSV in each group. Distal anastomoses were at the popliteal (15), peroneal (3), posterior (1), and anterior tibial (1) arteries in each group. Matching was not possible for lesser saphenous and cephalic vein grafts or bypasses to the tibial-peroneal trunk. Graft diameters were significantly larger for the PAA group, 6.24 +/-0.66 mm (standard deviation), than for the PAOD group, 5.73 +/-0.69 mm (p < 0.02, Mann-Whitney U test). Of 10 bypasses with diameter >6.5 mm, 8 were implanted for PAA. If these 10 largest bypasses were eliminated from the calculations, the mean graft diameters were 5.82 +/-0.51 mm and 5.57 +/-0.52 mm for the PAA and PAOD groups, respectively (p = 0.28). Bypass grafts implanted in PAA patients had significantly greater diameters than grafts implanted in PAOD patients. This finding, however, was due to a subgroup of grafts with diameters >6.5 mm. Perhaps systemic abnormalities associated with PAA should be first studied in patients with large vein grafts or large original veins.


Specific phenotyping of T-cell proliferations in formalin-fixed paraffin-embedded tissues. Use of antibodies to the T-cell receptor beta F1.
Antibody beta F1 to a common framework determinant of the beta subunit of the T-cell receptor (TCR) was used as a specific phenotypic marker for T-cell differentiation in malignant lymphomas. Sensitivity of immunoperoxidase staining in paraffin sections was enhanced by pronase pretreatment, overnight incubation of primary antibody in Tween 20, and use of streptavidin horseradish peroxidase complexes to amplify the reaction. All 43 cases of B-cell lymphoma were negative for TCR. Reed Sternberg (RS) cells in 3 of 20 cases of Hodgkin's disease exhibited cell membrane staining for TCR (all nodular sclerosis type), further evidence that some RS cells may be T-cell derived. Twenty-nine of 44 cases of T-cell lymphoma expressed TCR (66%). These included 11 of 12 cases of peripheral T-cell lymphoma (PTCL) of small and mixed cell type, 8 of 9 cases of lymphoepithelioid cell (Lennert's) lymphoma, and 2 of 4 cases of T-cell lymphoblastic lymphoma. Loss of immunoreactivity for TCR occurred in lymphomas of large or activated T-cell type, including 7 of 9 cases of T-cell immunoblastic lymphoma and 3 of 4 cases of large cell PTCL. Antibody beta F1 is a specific and relatively sensitive marker of T-cell phenotype in formalin-fixed paraffin sections of malignant lymphomas.


Management of disappearing colorectal liver metastases.
The development of new potent systemic treatment modalities has led to a significant increase in survival of patients with colorectal liver metastases. In the neo-adjuvant setting, these modalities can be used for patient selection, down staging, and conversion from non-resectable to resectable liver metastases. In addition, complete radiological disappearance of metastases can occur, the phenomenon of disappearing liver metastases. Because only a small percentage of these patients (0-8%) have a complete radiological response of all liver metastases, most patients will undergo surgery. At laparotomy, local residual disease at the site of the disappeared metastasis is still found in 11-67%, which highlights the influence of the imaging modalities used at (re)staging. When the region of the disappeared liver metastasis was resected, microscopically residual disease was found in up to 80% of the specimens. Alternatively, conservative management of radiologically disappeared liver metastases resulted in 19-74% local recurrence, mostly within two years. Obviously, these studies are highly dependent on the quality of the imaging modalities utilised. Most studies employed CT as the modality of choice, while MRI and PET was only used in selective series. Overall, the phenomenon of disappearing liver metastases seems to be a radiological rather than an actual biological occurrence, because the rates of macroscopic and microscopic residual disease are high as well as the local recurrence rates. Therefore, the disappeared metastases still require an aggressive surgical approach and standard (re)staging imaging modalities should include at least CT and MRI.


Dependence of NMR noise line shapes on tuning, matching, and transmission line properties.
The tuning and matching conditions of rf circuits, as well as the properties of the transmission lines connecting these to the preamplifier, have direct consequences for NMR probe sensitivity and as for the optimum delivery of rf power to the sample. In addition, tuning/matching conditions influence radiation damping effects, which manifest themselves as fast signal flip-back and line broadening effects, and can lead to concentration-dependent frequency shifts. Previous studies have also shown that the appearance of spin-noise and absorbed circuit noise signals heavily depended on tuning settings. Consequently, all these phenomena are linked together. The mutual connections and interdependences of these effects are highlighted and reviewed here.


American College of Radiology (ACR) and American Society for Radiation Oncology (ASTRO) practice guideline for the performance of total body irradiation (TBI).
Total body irradiation (TBI) is a specialized radiotherapy technique. It is frequently used as a component of treatment plans involving hematopoietic stem cell transplant for a variety of disorders, most commonly hematologic malignancies. A variety of treatment delivery techniques, doses, and fractionation schemes can be utilized. A collaborative effort of the American College of Radiology and American Society for Radiation Oncology has produced a practice guideline for delivery of TBI. The guideline defines the qualifications and responsibilities of the involved personnel, including the radiation oncologist, physicist, dosimetrist, and radiation therapist. Review of the typical indications for TBI is presented, and the importance of integrating TBI into the multimodality treatment plan is discussed. Procedures and special considerations related to the simulation, treatment planning, treatment delivery, and quality assurance for patients treated with TBI are reviewed. This practice guideline can be part of ensuring quality and safety in a successful TBI program.


Design and methods for a cluster-controlled trial conducted at sixty-eight daycare facilities evaluating the impact of "JolinchenKids - Fit and Healthy in Daycare", a program for health promotion in 3- to 6-year-old children.
The prevention of overweight and obesity during infancy is a highly relevant public health topic given the significant impact of childhood obesity on acute and chronic diseases, general health, and well-being in later stages of life. Apart from the family setting, daycare facilities (DFs) represent a key setting for health promotion among children under the age of six years. "JolinchenKids - Fit and Healthy in Daycare" is a multi-component program promoting physical activity (PA), healthy eating, and mental well-being in 3- to 6-year-old preschoolers at DFs, originally designed by the German health insurance AOK. To evaluate program effectiveness, a cluster-controlled trial involving 68 DFs is currently conducted. The objective of this article is to describe the background, study design, and aims of this trial. Sixty-eight DFs across Germany will be recruited to take part in the study, half of them serving as intervention DFs and half of them as delayed intervention control DFs (which receive the program upon completion of the study). At each DF, height, weight, and body composition, as well as motor skills, will be assessed in twenty 3- to 6-year-old children. Children's eating and PA habits, and mental well-being will be assessed via parental questionnaires. A subsample of children (i.e., at 24 DFs which are randomly selected within a geographic region) will be asked to wear accelerometers at their wrists to objectively measure PA over the course of seven days. To compare changes in body composition, motor skills, eating and PA habits, and mental well-being of children at intervention DFs with those observed among children at delayed intervention control DFs over one year, all measurements will take place at baseline and twelve months after the launch of the program at all DFs. This study investigates the influence of a health promotion program in the daycare setting on various outcomes, including body composition and objectively measured PA, in a nationwide sample of 3- to 6-year-old preschoolers. This study will provide evidence regarding the effectiveness of a multi-component program for health promotion in this setting and may provide insights into new strategies for preventing obesity in early life. German Clinical Trials Register DRKS00011065 (Date of registration 16-09-2016).


Silver(i) complexes with 1'-(diphenylphosphino)-1-cyanoferrocene: the art of improvisation in coordination.
1'-(Diphenylphosphino)-1-cyanoferrocene () reacts with silver(i) halides at a 1 : 1 metal-to-ligand ratio to afford the heterocubane complexes [Ag(μ3-X)(-κP)]4, where X = Cl (), Br (), and I (). In addition, the reaction with AgCl with 2 equiv. of leads to chloride-bridged dimer [(μ-Cl)2{Ag(-κP)2}2] () and, presumably, also to [(μ(P,N)-){AgCl(-κP)}]2 (). While similar reactions with AgCN furnished only the insoluble coordination polymer [(-κP)2Ag(NC)Ag(CN)]n (), those with AgSCN afforded the heterocubane [Ag(-κP)(μ-SCN-S,S,N)]4 () and the thiocyanato-bridged disilver(i) complex [Ag(-κP)2(μ-SCN-S,N)]2 (), thereby resembling reactions in the AgCl- system. Attempted reactions with AgF led to ill-defined products, among which [Ag(-κP)2(μ-HF2)]2 () and [(μ-SiF6){Ag(-κP)2}2] () could be identified. The latter compound was prepared also from Ag2[SiF6] and . Reactions between and AgClO4 or Ag[BF4] afforded disilver complexes [(μ(P,N)-)Ag(ClO4-κO)]2 () and [(μ(P,N)-)Ag(BF4-κF)]2 () featuring pseudolinear Ag(i) centers that are weakly coordinated by the counter anions. A similar reaction with Ag[SbF6] followed by crystallization from ethyl acetate produced an analogous complex, albeit with coordinated solvent, [(μ(P,N)-)Ag(AcOEt-κO)]2[SbF6]2 (). Ultimately, a compound devoid of any additional ligands at the Ag(i) centers, [(μ(P,N)-)Ag]2[B(C6H3(CF3)2-3,5)4]2 (), was obtained from the reaction of with silver(i) tetrakis[3,5-bis(trifluoromethyl)phenyl]borate. The reaction of Ag[BF4] with two equivalents of produced unique coordination polymer [Ag(-κP)(μ(P,N)-)]n[BF4]n (), the structure of which contained one of the phosphinoferrocene ligands coordinated as a P,N-chelate and the other forming a bridge to an adjacent Ag(i) center. All of these compounds were structurally characterized by single-crystal X-ray crystallography, revealing that the lengths of the bonds between silver and its anionic ligand(s) typically exceed the sum of the respective covalent radii, which is in line with the results of theoretical calculations at the density-functional theory (DFT) level, suggesting that standard covalent dative bonds are formed between silver and phosphorus (soft acid/soft base interactions) while the interactions between silver and the ligand's nitrile group (if coordinated) or the supporting anion are of predominantly electrostatic nature.


High Aldehyde Dehydrogenase Activity Identifies a Subset of Human Mesenchymal Stromal Cells with Vascular Regenerative Potential.
During culture expansion, multipotent mesenchymal stromal cells (MSCs) differentially express aldehyde dehydrogenase (ALDH), an intracellular detoxification enzyme that protects long-lived cells against oxidative stress. Thus, MSC selection based on ALDH-activity may be used to reduce heterogeneity and distinguish MSC subsets with improved regenerative potency. After expansion of human bone marrow-derived MSCs, cell progeny was purified based on low versus high ALDH-activity (ALDHhi ) by fluorescence-activated cell sorting, and each subset was compared for multipotent stromal and provascular regenerative functions. Both ALDHl ° and ALDHhi MSC subsets demonstrated similar expression of stromal cell (>95% CD73+ , CD90+ , CD105+ ) and pericyte (>95% CD146+ ) surface markers and showed multipotent differentiation into bone, cartilage, and adipose cells in vitro. Conditioned media (CDM) generated by ALDHhi MSCs demonstrated a potent proliferative and prosurvival effect on human microvascular endothelial cells (HMVECs) under serum-free conditions and augmented HMVEC tube-forming capacity in growth factor-reduced matrices. After subcutaneous transplantation within directed in vivo angiogenesis assay implants into immunodeficient mice, ALDHhi MSC or CDM produced by ALDHhi MSC significantly augmented murine vascular cell recruitment and perfused vessel infiltration compared with ALDHl ° MSC. Although both subsets demonstrated strikingly similar mRNA expression patterns, quantitative proteomic analyses performed on subset-specific CDM revealed the ALDHhi MSC subset uniquely secreted multiple proangiogenic cytokines (vascular endothelial growth factor beta, platelet derived growth factor alpha, and angiogenin) and actively produced multiple factors with chemoattractant (transforming growth factor-β, C-X-C motif chemokine ligand 1, 2, and 3 (GRO), C-C motif chemokine ligand 5 (RANTES), monocyte chemotactic protein 1 (MCP-1), interleukin [IL]-6, IL-8) and matrix-modifying functions (tissue inhibitor of metalloprotinase 1 & 2 (TIMP1/2)). Collectively, MSCs selected for ALDHhi demonstrated enhanced proangiogenic secretory functions and represent a purified MSC subset amenable for vascular regenerative applications. Stem Cells 2017;35:1542-1553.


[Last word on hormone replacement and breast cancer?].
A very large meta-analysis of the Collaborative Group on Hormonal Factors in Breast Cancer has revealed an increasing risk of breast cancer with longer durations of use of hormonal replacement therapy (HRT). This risk increase is restricted to current users of HRT or women who ceased use recently. A 35% increase of the relative risk of breast cancer was found after 5 years of HRT use or longer. After cessation of HRT use the excess breast cancer risk disappeared in 5 years, even after long durations of use. The risk increase was greater for women of normal or lean body weight than for more obese women. Tumours found in women who ever used HRT were diagnosed at a lower clinical stage, which suggests that enhanced screening might be involved. However, the increased breast cancer mortality in HRT users, as found in other studies, rather suggests a biologic mechanism Long-term use of HRT is not yet common in the Netherlands, but an increasing trend is present. Thus, the benefits of long-term use of HRT must be carefully weighted against the risks.


Effect of lyophilized prune extract on hyperhomocysteinemia in mice.
Altered homocysteine metabolism defined as hyperhomocysteinemia is implicated as pathogenic factor in several cardiovascular diseases and atherosclerosis. The purpose of this study was to investigate the efficacy of prune extract, a good source of phenolic antioxidants, on lowering plasma homocysteine level in male hyperhomocysteinemic mice from average weight of 28 g. The administration of lyophilized prune extract was carried out by intraperitoneal injection one day preceding and one hour before sacrifice of mice. Prune extract decreased significantly plasma homocysteine level, correlated with an increased activity of S-adenosylhomocysteine (SAH) hydrolase and NAD(P)H: quinone oxydoreductase-1 activities. Our results suggest a beneficial effect of prune extract on hyperhomocysteinemia with reduction of homocysteine level by its conversion on to SAH by S-adenosylhomocysteine hydrolase, which is activated by NAD+, a by-product of NAD(P)H: quinone oxydo reductase-1.


[Effect of gene transfer using nanoparticles as gene vector in different animal models].
To evaluate the effect of antisense monocyte chemotactic protein-1 (A-MCP-1) nanoparticles (NPs) as gene carrier on gene transfer in two kinds of animal models. Poly (lactic acid-co-glycolic acid) (PLGA) was used to make the NPs loaded with A-MCP-1 through a double-emulsion/solvent evaporation technique. NPs size was assessed by dynamic laser defractometer. The particle morphology was observed by scanning electron microscopy. DNA content in the NPs was measured by dissolving known amounts of NPs in chloroform and extracting DNA with water. In vitro release was performed in tris-EDTA buffer at 37 degrees C using double-chamber diffusion cells. The receiver buffer was replaced daily. The A-MCP-1 NPs was transfected into the cultured smooth muscle cells. PCR was used to evaluate the transfection of A-MCP-1. Cationic lipid (Lipofectamine) was used to transfect A-MCP-1 as control. After 48 hours incubation, cells were digested and examined by polymerase chain reaction. Twenty New Zealand white rabbits under jugular vein to artery bypass grafting procedure were divided into four groups: the first group received grafts treated with A-MCP-1 NPs, the second group received grafts treated with cationic liposome (dioleoyl trimethyl ammonium propane)-A-MCP-1, the third group received grafts treated with plasmid DNA, and the fourth group received grafts without transfection as control. Fourteen days after surgery the grafts were harvested. The expression of A-MCP-1 and its effect on MCP-1 in vein grafts were detected by dot blotting. The morphology of the grafts was investigated. To establish abdominal aortic aneurysms rats model, rats were randomly divided into three groups: A-MCP-1 NPs injection group, shame NPs injection group and control groups (without injection). Two weeks after surgery, diameter of abdominal aorta was measured and aortic tissue was obtained for PCR analysis to evaluate the A-MCP-1 expression. Western blot were applied to detect the inhibitory effect to the expression of MCP-1 mRNA and CD68 protein by A-MCP-1 NPs. NPs size ranged 198nm to 205nm with average around 201.4 nm. DNA content in the NPs was 4.14%. NPs showed steady release rate in vitro in Tris-EDTA solution. It released faster in the first week then maintained a slowly sustained release up to 16 days. In cell culture A-MCP-1 gene successfully transfected into smooth muscle cells by NPs vector. In vein grafting animal model, A-MCP-1 expression was detected in the vascular walls of NPs and cationic lipid treated groups. The degree of vascular hyperplasia in the gene NPs treated group was significantly lower than that in control group. There was no significant difference in the inhibition of intimal hyperplasia between NPs and cationic lipid treated groups. Two weeks after transfection in abdominal aortic aneurysm rats models, the abdominal aortic diameter of A-MCP-1 NPs injection group was (1.79 +/- 0.12) mm, significantly smaller than that of control groups [shame NPs group was (2.58 +/- 0.21) mm, and saline group was (2.63 +/- 0.29) mm] (P < 0.01). The expressions of MCP-1 mRNA and CD68 protein in A-MCP-1 NPs injection group were 12.5 +/- 1.5 and 17.6 +/- 2.1, which were much lower than those in control group [in shame NPs group, which were 35.7 +/- 4.5, 42.3 +/- 5.7 (P < 0.01), and saline group which is 32.4 +/- 3.9, 39.8 +/- 4.8 (P < 0.01)]. Specific band of A-MCP-1 was detected only in the A-MCP-1 NPs injection group by PCR. A-MCP-1 gene NPs can be successfully used in rabbit vein grafting model and abdominal aortic aneurysm rats models, and may be potentially applied in clinical practice.


[Epidemiological study on risk factors of cervical cancer].
The relationship between cervical cancer and risk factors including virus infection of cervix was studied with methods of molecular and serological epidemiology. DNA extracted from cervical biopsies taken from 57 cases and 51 controls were tested for HPV6/11, HPV16/18 by Dot-blot hybridization and for HSV-2 by PCR. Sera were detected for HCMV-IgM by ELISA. The results and risk factors were analyzed by logistic regression model. The multiple logistic regression model results showed that HPV16/18 infection was an important risk factor, the infection rate was significantly higher in the group of cervical cancer, the OR was 31.96. Other risk factors were the educational level and the number of birth, the OR were 0.57 and 1.85, respectively. The difference of HSV-2 infection of cervix and HCMV-IgM in serum was not significant between the two groups.


Why can't we just get along? Interpersonal biases and interracial distrust.
The authors review a series of studies that illustrate how one form of contemporary racial bias of Whites, aversive racism, can shape different perspectives of Blacks and Whites in ways that can undermine race relations. This research demonstrates that contemporary racism among Whites is subtle, often unintentional, and unconscious but that its effects are systematically damaging to race relations by fostering miscommunication and distrust. In particular, the authors examine the effects of aversive racism on outcomes for Blacks (e.g., in selection decisions), on the ways that Whites behave in interracial interactions, in the impressions that Whites and Blacks form of each other in these interactions, and on the task efficiency of interracial dyads.


Wavelength tunable InGaN/GaN nano-ring LEDs via nano-sphere lithography.
In this research, nano-ring light-emitting diodes (NRLEDs) with different wall width (120 nm, 80 nm and 40 nm) were fabricated by specialized nano-sphere lithography technology. Through the thinned wall, the effective bandgaps of nano-ring LEDs can be precisely tuned by reducing the strain inside the active region. Photoluminescence (PL) and time-resolved PL measurements indicated the lattice-mismatch induced strain inside the active region was relaxed when the wall width is reduced. Through the simulation, we can understand the strain distribution of active region inside NRLEDs. The simulation results not only revealed the exact distribution of strain but also predicted the trend of wavelength-shifted behavior of NRLEDs. Finally, the NRLEDs devices with four-color emission on the same wafer were demonstrated.


Steeper discounting of delayed rewards in schizophrenia but not first-degree relatives.
Excessive discounting of future rewards has been related to a variety of risky behaviors and adverse clinical conditions. Prior work examining delay discounting in schizophrenia suggests an elevated discount rate. However, it remains uncertain whether this reflects the disease process itself or an underlying genetic vulnerability, whether it is selective for delay discounting or reflects pervasive changes in decision-making, and whether it is driven by specific clinical dimensions such as cognitive impairment. Here we investigated delay discounting, as well as loss aversion and risk aversion, in three groups: schizophrenia (SZ), unaffected first-degree family members (FM), and controls without a family history of psychosis (NC). SZ had elevated discounting, without changes in loss aversion or risk aversion. Contrary to expectations, the FM group did not show an intermediate phenotype in discounting. Higher discount rates correlated with lower cognitive performance on verbal reasoning, but this did not explain elevated discount rates in SZ. Group differences were driven primarily by the non-smoking majority of the sample. This study provides further evidence for elevated discounting in schizophrenia, and demonstrates that steeper discounting is not necessarily associated with familial risk, cannot be wholly accounted for by cognitive deficits, and is not attributable to smoking-related impulsivity.


miR-92a promotes tumor growth of osteosarcoma by targeting PTEN/AKT signaling pathway.
MicroRNAs (miRNAs) play critical roles in human cancers including osteosarcoma (OS). miR-92a has been found to be a cancer-related miRNA in many cancer types and it is upregulated in OS cell lines. However, the expression and biological function of miR-92a in OS have not been investigated. In this study, we showed that miR-92a expression was increased in OS tissues, and its high expression was correlated with clinical stage, T classification and histological differentiation. Furthermore, patients with high expression of miR-92a had a significantly poorer survival rate. Functionally, miR-92a overexpression promoted the proliferation and cell cycle progression, and inhibited apoptosis in MG-63 cells. While inhibition of miR-92a showed contrary effects with reduced proliferation, cell cycle arrest at G1 phase and increased apoptosis in U2OS cells. Moreover, we confirmed that miR-92a inhibition reversed the tumor growth of OS cells in nude mice. Phosphatase and tensin homolog (PTEN), a well-known tumor suppressor, was confirmed to be the direct downstream target of miR-92a in OS. Notably, miR-92a consequently regulated the expression of the downstream targets of PTEN/AKT signaling pathway including p-Akt(Ser473), mTOR, p-p27(Thr157) and p-MDM2(Ser166). Furthermore, PTEN knockdown abrogated the functional effects of miR-92a silencing on the proliferation, apoptosis and cell cycle progression in OS cells. Thus, miR-92a that exerts an oncogenic role by targeting PTEN/AKT pathway in OS potentially acts as a biomarker and drug-target.


Evolutionary adaptation and stress: energy budgets and habitats preferred.
Natural populations are normally exposed to substantial environmental stress. The consequences of stress include elevated metabolic costs and additive genetic variability. From the former, preferred habitats should be located in environments corresponding to minimum total energy expenditure. This tendency occurs in the field for behavioral adaptation of Drosophila to variable temperature (and humidity) conditions. Laboratory studies of resource preference in Drosophila suggest a low genetic variability. However, under more stressful field conditions, genetic variability should be higher. Habitat preference studies under stressful conditions therefore need to be emphasized in modeling situations in nature.


Computational Study on the Reaction of β-Hydroxyethylperoxy Radical with HO2 and Effects of Water Vapor.
The reaction of β-hydroxyethylperoxy radical (β-HEP) and HO2 with and without water was studied using quantum chemistry and kinetic calculations. The main products are HOCH2CH2OOH and 3O2 for the reaction with and without water, while all other reaction channels can be neglected. The rate coefficients of the reaction follow negative temperature dependence. The pseudo-second-order rate coefficients are 2-4 orders of magnitude smaller for the reaction with saturated water vapor, indicating the negligible contribution of water in this reaction. This is probably also true for other peroxy radicals (except for HO2), indicating that a large part of previous results on the water enhancement of reaction rate coefficients might have overestimated the influence of water.


Abstinent alcoholics exhibit an exaggerated stress response to 2-deoxy-D-glucose challenge.
Chronic excessive alcohol consumption can significantly disturb the hypothalamic control of glucose metabolism; however, the mechanism and clinical significance of this disturbance are poorly understood. We used 2-deoxy-D-glucose (2-DG), which produces intracellular glucoprivation, to compare neurochemical, physiological, and behavioral responses to glucoprivic stress between alcoholics abstinent for 3 weeks and healthy volunteers. Twenty-six male alcoholics and 15 male healthy volunteers received intravenous infusions of placebo, 12.5 mg/kg, and 25.0 mg/kg of body weight of 2-DG over 30 min on three separate days, following a random-ordered, double-blind procedure. Minimal effects were observed following administration of the 12.5 mg/kg of body weight dose of 2-DG. Following 25.0 mg/kg, alcoholics showed both exaggerated ACTH and cortisol responses and greater increases in caloric intake when compared with controls. Although anxiety, desire to consume alcohol, plasma progesterone, and sympathetic and adrenal medullary activity all increased following 2-DG, these responses did not differ between alcoholics and controls. The present findings suggest certain specificity for the exaggerated hypothalamic and adrenocortical responses to mild glucoprivic stress in 3-week-abstinent alcoholics.


Male emotional intimacy: how therapeutic men's groups can enhance couples therapy.
Men's difficulty with emotional intimacy is a problem that therapists regularly encounter in working with heterosexual couples in therapy. The first part of this article describes historical and cultural factors that contribute to this dilemma in men's marriages and same-sex friendships. Therapeutic men's groups can provide a corrective experience for men, helping them to develop emotional intimacy skills while augmenting their work in couples therapy. A model for such groups is presented, including guidelines for referral, screening, and collaboration with other therapists. Our therapeutic approach encourages relationship-based learning through direct emotional expression and supportive feedback. We emphasize the development of friendship skills, core attributes of friendship (connection, communication, commitment, and cooperation) that contribute to emotional intimacy in men's relationships. Case examples are included to illustrate how this model works in clinical practice, as well as specific suggestions for further study that could lead to a more evidence-based practice.


Clinical improvement after Essure® devices removal: a systematic review.
Essure® implant is a permanently implanted minimally invasive birth control device for women (female sterilisation) widely used between 2002 and 2018. Many adverse events were reported by patients. Increasingly removal procedures have been performed in symptomatic patients. However, there is a lack of in-depth studies on clinical improvement after Essure® removal. We aimed to review all clinical studies about symptoms and quality of life (QoL) after removal procedures. A review of literature in electronic search in Medline and Embase databases from January 2002 to January 2022 using the following keywords: Essure; Essure removal; quality of life; symptomatology improvement. Out of 764 articles in the initial database, 18 clinical studies were eligible for inclusion in our literature review. Overall clinical improvement rates after removal ranged from 21% to 98%. All symptoms were less frequent after Essure® removal, although with large discrepancies between studies. Lack of improvement was reported between 1% to 15% of patients. Rate of patients with improvement of QoL after removal ranged from 58 to 98%. The pain was reported as significantly reduced after the surgery. In the available literature, Essure® removal in symptomatic patients may improve symptoms and quality of life. This should be discussed in the benefits and risks ratio before deciding on the best option of management.


Transcriptomic Profiling Highlights the ABA Response Role of BnSIP1-1 in Brassica napus.
BnSIP1-1 is the first identified SIP1 (6b Interacting Protein1) subfamily gene of the trihelix transcription factor family from Brassica napus (B. napus). We previously used a reverse genetic method to reveal its abiotic stress response function in endowing plants resistance to drought and salinity, as well as ABA (Abscisic acid). However, the molecular mechanisms of BnSIP1-1 are unclear. In this study, the global transcriptome files of BnSIP1-1-overexpressing transgenic and wildtype B. napus seedlings under ABA treatment were constructed using RNA-seq. A total of 1823 and 5512 DEGs (Differentially Expressed Genes) were identified in OE vs. WT and OE_ABA vs. WT_ABA comparison groups, which included 751 and 2567 up-regulated DEGs, and 1072 and 2945 down-regulated DEGs, separately. The impact of overexpressed BnSIP1-1 on plants was amplified by ABA, indicating BnSIP1-1 was an ABA-conditioned responsive gene. More interestingly, we found the reasons for BnSIP1-1 increasing plants' insensitivity to ABA were not by regulating ABA synthesis and catabolism, but by manipulating ABA transportation, ABA signal perception and transduction, inositol phosphate metabolism, as well as endomembrane trafficking, indirectly suggesting this gene may play roles upstream of the core ABA response pathway. Our results provided new insights into improving the knowledge about the function of BnSIP1-1 and the ABA signaling mechanism in B. napus.


HLA-antigens in black patients with hepatocellular carcinoma.
To determine whether genetically determined immune response factors could be involved in the pathogenesis of hepatocellular carcinoma, we performed HLA-A and HLA-B typing in 55 black patients with histologically-proven hepatocellular carcinoma, and HLA-DR and HLA-DQ typing in 47 of these patients. The HLA typing was also carried out in a control group of normal black patients. The HLA typing was done by a standard microlymphocytotoxicity method. No difference in HLA-A, HLA-DR and HLA-DQ frequencies between patients and controls were noted. HLA-B21 was present in 10.9% of patients compared to 1.8% of control subjects (corrected p < 0.005; relative risk = 6.6) and HLA-B49 was present in 7.3% of patients compared with 1.1% of normal control subjects (corrected p < 0.007; relative risk = 7.1). These findings suggest that genetic factors may play a role in the pathogenesis of hepatocellular carcinoma.


Enhanced cytotoxicity of bleomycin, cisplatin, and carboplatin on equine sarcoid cells following electroporation-mediated delivery in vitro.
Electroporation is a method used to deliver poorly permeant chemotherapeutic drugs to tumor cells, potentiating the cytotoxic effects of drugs and overall clinical response. Despite existing evidence of the potential benefits of electroporation to enhance the antitumoral effects of drugs, there is a lack of understanding about the effects of electroporation on equine tumor cells. This study investigated the combined effects of electroporation and bleomycin, cisplatin, and carboplatin on an equine sarcoid cell line (EqS04b). The use of electroporation increases the cytotoxic effects of bleomycin, cisplatin, and carboplatin on the equine sarcoid cell line by 5-fold, 4-fold, and 3-fold, respectively. These very promising findings demonstrate proof of principle for future preclinical studies on different tumor cells to investigate the in vivo effects of electroporation in sarcoid tumors.


Rationale, Design and Methods of the Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) Study.
The optimal timing of anticoagulation following acute ischaemic stroke or TIA in patients with atrial fibrillation (AF) is a frequent challenge. Early initiation of anticoagulation can reduce the risk for recurrent ischaemic events, but may lead to an increased risk for intracerebral haemorrhage. The Prospective Record of the Use of Dabigatran in Patients with Acute Stroke or TIA (PRODAST) study was initiated to investigate outcome events under antithrombotic therapy after ischaemic stroke or TIA in patients with AF. The main objective is to compare the three-month rates of major haemorrhagic events between early (≤ 7 days) versus late (> 7 days) administration of dabigatran or treatment with vitamin-K antagonists started at any time. Occurrences of ischaemic and major haemorrhagic events will be evaluated to determine the optimal time point for initiation or resumption of anticoagulation. PRODAST is a prospective, multicenter, observational, non-interventional post-authorization safety study. 10,000 patients with recent (≤ 1 week from index event) ischaemic stroke or TIA and non-valvular AF were recruited at 86 German sites starting in July 2015. The observational plan includes a baseline visit, documentation of data during hospitalization and a telephone-based, central follow-up at three months after the index event. The primary endpoint is the major bleeding rate within three months. Secondary endpoints include rates of recurrent ischaemic or haemorrhagic stroke, TIA, systemic embolism, myocardial infarction and death. PRODAST will provide important real-world data on safety and efficacy of antithrombotic therapy after acute stroke and TIA in patients with AF.


Highly Propylene-Selective Mixed-Matrix Membranes by in Situ Metal-Organic Framework Formation Using a Polymer-Modification Strategy.
Despite the potential of C3H6/C3H8 separation, there have been no industrial applications of zeolitic-imidazole framework-8 (ZIF-8) mixed-matrix membranes (MMMs) because of the moderate separation performances and several challenging processing issues. Herein, we present a new paradigm of MMM fabrication, named polymer-modification-enabled in situ metal-organic framework formation (PMMOF), enabling in situ formation of ZIF-8 fillers inside the 4,4-(hexafluoroisopropylidene)diphthalic anhydride 2,4,6-trimethyl-1,3-phenylenediamine polymer. PMMOF consists of four steps including hydrolysis of a polymer, ion-exchange, ligand treatment, and imidization. Each step was thoroughly analyzed and important processing parameters were identified, enabling the structural control of MMMs by PMMOF. The binary C3H6/C3H8 separation performance of the MMMs showed much higher separation factors than conventionally prepared MMMs at similar filler loadings, satisfying the commercial C3H6/C3H8 separation performance criteria. PMMOF was successfully applied for other MOFs, demonstrating that the process could be general. Finally, as a proof of concept, asymmetric mixed-matrix hollow fiber membranes (i.d. of 0.45 mm and o.d. of 0.63 mm) with ultrathin selective skin layers were prepared by PMMOF, showing C3H6 permeance of 2.17 GPU and C3H6/C3H8 separation factor of ∼20.


Relationship separation for young, at-risk couples: prediction from dyadic aggression.
Dyadic physical aggression in the relationships of 158 young, at-risk couples was examined as a predictor of relationship separation over the course of 6 years. A high prevalence of physical aggression and a high rate of separation were found, with 80% of couples engaging in physical aggression (as reported by either partner or as observed) and 62% separating over time. As predicted, physical aggression significantly increased the likelihood of relationship dissolution, even after accounting for psychological aggression, prior relationship satisfaction, and relationship contextual factors (length of relationship, relationship type, and children in the household). Of the contextual factors, relationship type was predictive of relationship dissolution: Married couples were least likely to dissolve their relationships compared with cohabiting and dating couples.


Corneal hysteresis and intraocular pressure are altered in silicone-hydrogel soft contact lenses wearers.
The aim of this work is to determinate the effects in the physical parameters in terms of intraocular pressure (IOP) and central corneal thickness (CCT) and corneal biomechanics in terms of corneal resistance factor (CRF) and corneal hysteresis (CH) of wearing silicone-hydrogel soft contact lenses (SiH-CLs) in young adult subjects during a short-term follow-up. 40 eyes of 20 healthy patients with a mean age of 22.87 ± 4.14 were involved in this study. Subjects with corneal diseases, dry eye, irregular astigmatism or who have been previous contact lens wearers were excluded. The ocular response analyzer (Reichert Ophthalmic Instruments) was used to measure CH, CRF and IOP and Scheimpflug imaging (the GALILEI™ Dual Scheimpflug camera analyzer, Ziemer) was used to measure CCT before and 10 days (Group 1) and 20 days (Group 2) after wearing the SiH-CLs. IOP was significantly decreased 10 days after using the SiH-CLs (p = 0.009). Within the 20 days' period, Group 2 revealed an even more pronounced decrease in IOP (p = 0.003) while CH increased significantly (p = 0.04). CCT and CRF did not show a significant change during the period of SiH-CLs use. Our finding allowed obtaining an empirical expression that relates IOP, CCT, CRF and CH within a biomechanical compensation experimental model. Corneal biomechanical parameters and physical properties of the cornea may be altered due to SiH-CLs use. Our findings could have an impact on the management of glaucoma progression and ocular hypertension.


Impact of robotics and human enhancement on occupation: what does it mean for rehabilitation?
Purpose: People with disabilities face participation challenges in all occupations. Scientific and technological advancements impact the occupational landscape of humans. This scoping review aimed to ascertain the academic engagement with occupation in relation to robotics and human enhancement focusing in particular on how people with disabilities and rehabilitation were mentioned.Method: SCOPUS and the 70 databases of EBSCO host were searched. Manifest and latent content coding and thematic grouping of codes relevant to answering the review questions was performed.Results: Only four articles engaged with occupation in relation to human enhancement. As to occupation and robotics, some occupational fields were visible and not others; occupational health and safety was the most visible one; people with disabilities were covered from a medical, therapeutic angle and not in relation to social issues caused by the occupational impact of robotics. Change in the scope, meaning, and clients of rehabilitation efforts related to occupation enabled by human enhancement and robotics was not covered.Conclusions: The gaps found should be filled. The impact of robotics and human enhancement on the occupational landscape indicates the need for rehabilitation to think beyond recovery to the species typical as a goal. The ultrabilitation concept could help to meet this need.Implications for rehabilitationAdvances in robotics and human enhancement beyond species-typical levels modify the occupational landscape, human ability expectations in this setting, and the meaning and scope of disability and rehabilitation (clinical and community based).There is a need to elucidate the impact of these changes on the meaning, scope and goals of recovery-oriented rehabilitation.The recently coined term "ultrabilitation" creates space to discuss an ability expectation creep triggered by developments in robotics and human enhancement, particularly within occupation focused rehabilitation.


Reasons for the degeneration of ageing skeletal muscle: a central role for IGF-1 signalling.
This paper examines two major possibilities for the striking loss of skeletal muscle mass and strength that occurs in very old animals and humans. It is concluded that muscle regeneration is not significantly impaired with age. Instead, it seems that individual myofibres undergo atrophy, with selective death of the fast type 2B myofibres, due to the combined effects of many age-related changes the main causes being: nutrition (under-nutrition and lack of vitamin D), decreased hormone levels (e.g growth hormone, testosterone), reduced physical activity, and a loss of nerves that innervate the muscles. The discussion focusses on the central role of a local muscle form of insulin-like growth factor-I (IGF-I) in muscle hypertrophy, atrophy and motorneurone loss. Reduced IGF-I signalling is involved in muscle atrophy and results from decreased muscle exercise, reduced growth hormone and insulin levels, reduced vitamin D, and treatment with drugs like corticosteroids, dexamethasone, and cyclosporin. In addition, elevated levels of inflammatory cytokines like TNF-alpha and IL-6 can cause muscle wasting (cachexia) although this is usually associated with disease, and TNF-alpha may also act (at least in part) by inhibiting IGF-I signalling. The possible clinical prevention of age-related muscle wasting (and associated motorneurone loss) by the locally acting muscle isoform of IGF-I is discussed.


Dim light adaptation attenuates acute melatonin suppression in humans.
Abstract Studies in rodents with retinal degeneration indicated that neither the rod nor the cone photoreceptors obligatorily participate in circadian responses to light, including melatonin suppression and photoperiodic response. Yet there is a residual phase-shifting response in melanopsin knockout mice, which suggests an alternate or redundant means for light input to the SCN of the hypothalamus. The findings of Aggelopoulos and Meissl suggest a complex, dynamic interrelationship between the classic visual photoreceptors and SCN cell sensitivity to light stimuli, relative to various adaptive lighting conditions. These studies raised the possibility that the phototransductive physiology of the retinohypothalamic tract in humans might be modulated by the visual rod and cone photoreceptors. The aim of the following two-part study was to test the hypothesis that dim light adaptation will dampen the subsequent suppression of melatonin by monochromatic light in healthy human subjects. Each experiment included 5 female and 3 male human subjects between the ages of 18 and 30 years, with normal color vision. Dim white light and darkness adaptation exposures occurred between midnight and 0200 h, and a full-field 460-nm light exposure subsequently occurred between 0200 and 0330-h for each adaptation condition, at 2 different intensities. Plasma samples were drawn following the 2-h adaptation, as well as after the 460-nm monochromatic light exposure, and melatonin was measured by radioimmunoassay. Comparison of melatonin suppression responses to monochromatic light in both studies revealed a loss of significant suppression after dim white light adaptation compared with dark adaptation (p < 0.04 and p < 0.01). These findings indicate that the activity of the novel circadian photoreceptive system in humans is subject to subthreshold modulation of its sensitivity to subsequent monochromatic light exposure, varying with the conditions of light adaptation prior to exposure.


A population-based analysis of Head and Neck hemangiopericytoma.
Hemangiopericytomas (HPC) are tumors that arise from pericytes. Hemangiopericytomas of the head and neck are rare and occur both extracranially and intracranially. This study analyzes the demographic, clinicopathologic, treatment modalities, and survival characteristics of extracranial head and neck hemangiopericytomas (HN-HPC) and compares them to HPCs at other body sites (Other-HPC). The Surveillance, Epidemiology, and End Results (SEER) database (1973-2012) was queried for HN-HPC (121 cases) and Other-HPC (510 cases). Data were analyzed comparatively with respect to various demographic and clinicopathologic factors. Disease-specific survival (DSS) was analyzed using the Kaplan-Meier model. There was no significant difference in age at time of diagnosis between HN-HPC and Other-HPC. Head and neck HPC was most commonly located in the connective and soft tissue (18.4%), followed by the nasal cavity and paranasal sinuses (8.5%). Head and neck HPCs were smaller than Other-HPC (P < 0.0001) and more likely to be a lower histologic grade (P < 0.0097). The primary treatment modality for HN-HPC was surgery alone, used in 55.8% of cases. The 5-, 10-, and 20-year DSS for HN-HPC were 84.0%, 79.4%, and 69.4%, respectfully. Higher histologic grade and the presence of distant metastases were poor prognostic factors for HN-HPC. Head and neck HPCs are rare tumors. This study represents the largest series of HN-HPCs to date. Surgery alone is the primary treatment modality for HN-HPC, with a favorable prognosis. Adjuvant radiotherapy does not appear to confer a survival benefit for any body site. 4. Laryngoscope, 126:643-650, 2016.